Article

Relationship of Right- to Left-Sided Ventricular Filling Pressures in Advanced Heart Failure Insights From the ESCAPE Trial

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

Background: Although right atrial pressure (RAP) and pulmonary capillary wedge pressure (PCWP) are correlated in heart failure, in a sizeable minority of patients, the RAP and PCWP are not tightly coupled. The basis of this variability in the RAP/PCWP ratio, and whether it conveys prognostic value, is not known. Methods and results: We analyzed the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial database. Baseline characteristics, including echocardiographic assessment of right ventricular (RV) structure and function, and invasively measured hemodynamic parameters, were compared among tertiles of the RAP/PCWP ratio. Multivariable Cox proportional hazard models assessed the association of RAP/PCWP ratio with the primary ESCAPE outcome (6-month death or hospitalization [days]) adjusting for systolic blood pressure, blood urea nitrogen, 6-minute walk distance, and PCWP. The RAP/PCWP tertiles were 0.27 to 0.4 (tertile 1); 0.41 to 0.615 (tertile 2), and 0.62 to 1.21 (tertile 3). Increasing RAP/PCWP was associated with increasing median right atrial area (23, 26, 29 cm2, respectively; P<0.005), RV area in diastole (21, 27, 27 cm2, respectively; P<0.005), and pulmonary vascular resistance (2.4, 2.9, 3.6 woods units, respectively; P=0.003), and lower RV stroke work index (8.6, 8.4, 5.5 g·m/m2 per beat, respectively; P<0.001). RAP/PCWP ratio was associated with death or hospitalization within 6 months (hazard ratio, 1.16 [1, 1.4]; P<0.05). Conclusions: Increased RAP/PCWP ratio was associated with higher pulmonary vascular resistance, reduced RV function (manifest as a larger right atrium and ventricle and lower RV stroke work index), and an increased risk of adverse outcomes in patients with advanced heart failure.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... Several factors such as etiology of heart failure, duration of the disease, presence of concomitant valvular or pulmonary disorders as well as severity of right ventricular (RV) dysfunction may cause discordance between right-and left-side filling pressures. [3,[6][7][8][9] The relationship between the right and left heart filling pressures can also be expressed as the ratio between the RAP and PCW pressure (PCWP) (RAP/PCWP ratio). This ratio is associated with mortality, heart failure decompensation, and cardiorenal syndrome. ...
... Furthermore, HFPEF patients had dominant high-R mismatch in Drazner et al. and Horiuchi et al. studies. [2,8,9,22] Although a small sample size could be the reason of a lower number of patients with high left mismatch profile in the HFMREF and HFPEF groups, the findings would point to higher prevalence of right heart dysfunction in these two groups of heart failure patients. ...
... Many investigations have shown a higher predictive value of RA/PCWP ratio than RA or PCWP alone in prediction of hospitalization, renal failure, post-heart surgery RV failure, and mortality in patients with heart failure and pulmonary hypertension regardless of the etiology. [9][10][11]13] ...
Article
Introduction: The prognostic significance of filling pressures and the relationship between left and right heart filling pressures have been well characterized in patients with heart failure. In the present study, we sought to evaluate the prevalence of discordance between left- and right-sided filling pressures and their relationship with clinical characteristics, laboratory data, and outcome measures (mortality and heart transplantation) in patients who were registered in right heart catheterization registry of Rajaie Heart Center (RHC-RHC registry). Methods: The hospital information system was queried for all adult patients with diagnosis of chronic heart failure who had undergone right heart catheterization between July 2009 and July 2019 in heart failure and transplantation department. The following variables were measured for each patient: mean right atrial pressure; systolic and end-diastolic right ventricular pressures; systolic, diastolic, and mean pulmonary artery pressure; pulmonary capillary wedge pressure (PCWP); mixed venous oxygen saturation; and cardiac output and cardiac index by Fick technique. The RAP/PCWP ratio was also calculated. The outcome of interest was all-cause mortality and heart transplantation after the index right heart catheterization. All of the patients were monitored for all-cause mortality or heart transplantation until July 2020. Results: Among 1941 patients, a total of 1078 patients (75% male) were selected. The mean (standard deviation) of age was 42.7 (15.7) years. Heart failure reduced ejection fraction (HFREF) was found in the majority of patients (85.1%), with nonischemic dilated cardiomyopathy and ischemic cardiomyopathy being the most frequent etiologies. The concordance between right and left filling pressures is more noticeable in patients with HFREF and heart failure mildly reduced EF than in patients with heart failure preserved EF (HFPEF). The median (interquartile range) of follow-up duration was 24 (6–48) months. During the follow-up time, 676 (62.7%) patients met the study outcomes of interest within
... 3) the absence of pre-specified pressure targets allowed clinicians to leave PAPs in a range high above normal in many patients; and 4) NYHA functional and end-diastolic PAP showed a significant correlation between the 2; however, the correlation proved to be inaccurate when the pulmonary vascular resistance was elevated (39). Although both systolic and diastolic PAP were shown to correlate relatively well with pulmonary capillary wedge pressure (PCWP) (38,40,41), in patients with advanced heart failure, left-and right-sided filling pressures were found to be mismatched (42,43). Moreover, this discordance was related to an increased risk of poor outcomes (44). ...
... This implies, on a physiological level, that PAP measurement alone may be an inaccurate indicator of LVEDP for many patients with heart failure, especially for those who also experience contributing factors, such as lung disease and thromboembolism. At the very least, any difference between PAP and LAP must be taken into account in treatment decisions.It is possible that the frequency and timing of pressure monitoring have an influence on the efficiency of heart failure management according to PAP.Although algorithms based on infrequent or 1-time PAP or PCWP measurement using right heart catheterization seem to be inefficient in improving outcomes(43), daily measurements conducted on an outpatient basis can improve outcomes(26), mainly because they enable identification of a slow rise in pressure over longer periods of time, the indicator that best correlates with HF hospitalization risk.Finally, there are specific cases in which LAP monitoring might contribute valuable information regarding conditions frequently associated with heart failure. An important example is functional (or secondary) mitral regurgitation, which is associated with left ventricular enlargement and dysfunction. ...
Article
Full-text available
Rates of heart failure hospitalization remain unacceptably high. Such hospitalizations are associated with substantial patient, caregiver, and economic costs. Randomized controlled trials of noninvasive telemedical systems have failed to demonstrate reduced rates of hospitalization. The failure of these technologies may be due to the limitations of the signals measured. Intracardiac and pulmonary artery pressure–guided management has become a focus of hospitalization reduction in heart failure. Early studies using implantable hemodynamic monitors demonstrated the potential of pressure-based heart failure management, whereas subsequent studies confirmed the clinical utility of this approach. One large pivotal trial proved the safety and efficacy of pulmonary artery pressure–guided heart failure management, showing a marked reduction in heart failure hospitalizations in patients randomized to active pressure-guided management. “Next-generation” implantable hemodynamic monitors are in development, and novel approaches for the use of this data promise to expand the use of pressure-guided heart failure management.
... Several subsequent studies have demonstrated the utility of the ratio of RA pressure to pulmonary capillary wedge pressure as an index of biventricular congestion and the relative contribution of LV or RV failure among patients with acute myocardial infarction and advanced heart failure and as a predictor of RV failure after LVAD implantation. 13,30,38,39 RV stroke work is another important measure of RV function; however, calculation of RV stroke work requires a true estimate of cardiac output, which is commonly measured with the Fick method in RV failure. The method of thermodilution may underestimate cardiac output as a result of tricuspid regurgitation. ...
... The method of thermodilution may underestimate cardiac output as a result of tricuspid regurgitation. 38,40 Multiple formulas to assess pulmonary hemodynamics have been developed to quantify RV afterload, including pulmonary vascular resistance, transpulmonary gradient, diastolic pulmonary gradient, PA elastance, PA compliance, and PA impedance. 15,33,34,36,37,41 However, none of these formulas in isolation definitively identifies RV failure. ...
Article
Right ventricular (RV) failure remains a major cause of global morbidity and mortality for patients with advanced heart failure, pulmonary hypertension, or acute myocardial infarction and after major cardiac surgery. Over the past 2 decades, percutaneously delivered acute mechanical circulatory support pumps specifically designed to support RV failure have been introduced into clinical practice. RV acute mechanical circulatory support now represents an important step in the management of RV failure and provides an opportunity to rapidly stabilize patients with cardiogenic shock involving the RV. As experience with RV devices grows, their role as mechanical therapies for RV failure will depend less on the technical ability to place the device and more on improved algorithms for identifying RV failure, patient monitoring, and weaning protocols for both isolated RV failure and biventricular failure. In this review, we discuss the pathophysiology of acute RV failure and both the mechanism of action and clinical data exploring the utility of existing RV acute mechanical circulatory support devices.
... We did not find a significant correlation between PASP and BUN but these were the only two parameters that were predictive for readmission among this study population. However, the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial showed that increasing right arterial pressure(RAP)/pulmonary capillary wedge pressure(PCWP) was associated with the elevated in-hospital BUN, discharge BUN and creatinine (P≤0.005 for all) [22]. It is also important to note that the ESCAPE trial, involved patients with advanced HF, most of whom had elevated PCWPs and the increasing RAP/PCWP ratio resulted from increasing RAP. ...
Article
Full-text available
Objectives: To identify predictors of pulmonary hypertension (PHT) and the predictive value of PHT for re-hospitalization among patients with heart failure with reduced ejection fraction (HFrEF). Methods: A retrospective study of 351 hospitalized patients with heart failure (HF). Patients 18 years and above with HFrEF secondary to non-ischemic cardiomyopathy were reviewed. Patients with coronary artery disease, preserved ejection fraction and other secondary causes of PHT apart from HF were excluded. PHT as a predictor of 30-day and six-month re-admission was assessed as well as important possible predictors of PHT. Cox regression analysis, multiple linear regression as well as other statistical tools were employed as deemed appropriate. Results: Thirty-seven (37) and 99 patients were re-hospitalized within 30 days and 6 months after discharge for decompensated HF respectively. After Cox regression analysis, higher hemoglobin reduced odds of re-hospitalization for decompensated HF (p = 0.015) within 30 days after discharge while higher pulmonary artery systolic pressure (PASP) (p = 0.002) and blood urea nitrogen (BUN) (p = 0.041) increased the odds of re-hospitalization within 6 months of discharge. The predictors of the PHT among patients with HFrEF after multiple linear regression were low BMI (p = 0.027), increasing age (p = 0.006) and increased left atrial diameter (LAD) on echocardiography (p = 0.0001). Conclusion: Patients with HFrEF have a high predisposition to developing PHT if at admission, they have low BMI, dilated left atrium or are older. Patients with one or more of these attributes may need more intensive therapy to reduce the risk of developing PHT and in turn reduce readmission rates.
... In these patients, even a mild reduction in cardiac output also increases the pressure in the right atrium, the ratio between right atrial pressure to pulmonary capillary wedge pressure and also increases the venous return owing to the fluid overload. Accordingly, the right cardiac filling pressure is further increased and the left ventricle is relatively underfilled (in diastole) with consequent further impairment of forward output [98,118,137,176,177]. ...
Article
Full-text available
It is well known that the heart and kidney and their synergy is essential for hemodynamic homeostasis. Since the early XIX century it has been recognized that cardiovascular and renal diseases frequently coexist. In the nephrological field, while it is well accepted that renal diseases favor the occurrence of cardiovascular diseases, it is not always realized that cardiovascular diseases induce or aggravate renal dysfunctions, in this way further deteriorating cardiac function and creating a vicious circle. In the same clinical field, the role of venous congestion in the pathogenesis of renal dysfunction is at times overlooked. This review carefully quantifies the prevalence of chronic and acute kidney abnormalities in cardiovascular diseases, mainly heart failure, regardless of ejection fraction, and the consequences of renal abnormalities on both organs, making cardiovascular diseases a major risk factor for kidney diseases. In addition, with regard to pathophysiological aspects, we attempt to substantiate the major role of fluid overload and venous congestion, including renal venous hypertension, in the pathogenesis of acute and chronic renal dysfunction occurring in heart failure. Furthermore, we describe therapeutic principles to counteract the major pathophysiological abnormalities in heart failure complicated by renal dysfunction. Finally, we underline that the mild transient worsening of renal function after decongestive therapy is not usually associated with adverse prognosis. Accordingly, the coexistence of cardiovascular and renal diseases inevitably means mediating between preserving renal function and improving cardiac activity to reach a better outcome.
... Severe right-sided heart failure can also damage the liver, which is responsible for nutritional management in the body due to congestion, contributing to malnutrition and sarcopenia. Therefore, additional evaluation of the parameters of right ventricular function and right ventricular pressure (TAPSE, PAP, and right atrial pressure) by echocardiography and Swan-Ganz catheterization may further stratify the risk in HF patients [22][23][24]. In addition, the prognostic impact of malnutrition on HF patients was not evaluated in this study by using the Mini Nutritional Assessment (MNA), Prognostic Nutrition Index (PNI) and Controlling Nutritional Status (CONUT), Subjective Global Assessment (SGA), and Nutritional Risk Screening (NRS) 2012 [25][26][27][28][29]. Another limitation is that arm circumference, which has been reported to improve the prognosis of heart failure patients when assessed together with BMI, was not measured [30]. ...
Article
Full-text available
Although it is known that assessment and management of the nutritional status of patients are important for treatment of patients with heart failure (HF), there are currently no established indicators. Therefore, we investigated the effects of nutritional parameters as well as conventional parameters on the prognosis of HF patients. A total of 1954 consecutive HF patients with left ventricular ejection fraction (LVEF) less than 50% were enrolled in this study. Transthoracic echocardiography was performed and conventional parameters for HF patients and parameters to assess nutritional status were measured in all patients. Patients were followed up with a primary endpoint of lethal cardiac events (CEs) for 30.2 months. During the follow-up period, cardiac events were documented in 619 HF patients. The CEs group had a lower level of cholinesterase (201.5U/L vs 265.2U/L, P <0.0001), lower estimated GFR (35.2 ml/min/1.73m ² vs 50.3ml/min/1.73m ² , P< 0.0001), and lower Geriatric Nutritional Risk Index (GNRI) (91.9 vs 100.0, P< 0.0001) than those in the non-CEs group. Serum cholinesterase, estimated GFR, and GNRI were identified as significant prognostic determinants in multivariate analysis. ROC analyses revealed cut-off values of serum cholinesterase, estimated GFR, and GNRI of 229U/L, 34.2 ml/min/1.73m ² , and 95.6, respectively, for identifying high-risk HF patients. HF patients with serum cholinesterase< 229U/L, estimated GFR<34.3 ml/min/1.73m ² , and GNRI< 95.6 had a significantly greater rate of CEs than that in the other patients (P<0.0001). Low serum cholinesterase and low GNRI can predict cardiac mortality risk in systolic HF patients with renal dysfunction.
... Right heart catheterizations provide a variety of hemodynamic indices that stratify mortality risk including right atrial pressure (RAP), PAP, and PCWP. An elevated RAP:PCWP ratio ≥ 0.62 has been shown to be associated with death or hospitalization in HF patients with reduced EF [56]. Right ventricular stroke work index (RVSWI) [57,58] and pulmonary artery pulsatility index (PAPi) [59][60][61] are additional hemodynamic measurements that can provide a reliable quantification of RV function, along with prognostic information regarding survival and readmissions. ...
Article
Full-text available
Right ventricular (RV) function in patients with preexisting left ventricular (LV) systolic dysfunction is key to determining prognosis and identifying appropriate candidates for cardiac replacement therapy. This becomes particularly relevant during selection for left ventricular assist device (LVAD) therapy, since adequate cardiac output, differently from heart transplantation, still relies on native RV function. Importantly, accumulating evidence indicates that RV failure (RVF) carries detrimental consequences of progressive end-organ dysfunction due to systemic venous congestion-mediated inflammation and oxidative stress. Therefore, it is crucial to detect RVF early on in the disease state through heightened clinical suspicion and noninvasive and/or invasive modalities before the RV fails and organ damage ensues, precluding patients from life saving measures such as LVAD therapy. The purpose of this review is to discuss the pathogenesis of RVF, its systemic consequences, implications for pre- and post-LVAD management, and its impact on clinical outcomes.
... Interestingly, we did not find significant changes in RVSWI throughout the period of followup. In contrast, the trend of RAP/PCWP ratio, which is also known as a marker of RV dysfunction, 16 CO is being sustained artificially by an LVAD. In contrast, PAPI is a more specific measurement of the reduced pulsatility generated by the RV in this circumstance and may be better at capturing the degree of RV dysfunction independently from overall CO. 17 Whether PAPI or RVSWI predict subsequent admissions for RVF should be investigated in future studies. ...
Article
Full-text available
Background: Continuous-flow left ventricular assist devices (LVADs) improve the hemodynamics of patients with advanced heart failure. However, longitudinal trajectories of hemodynamics in LVAD patients remain unknown. The aim of this study was to investigate the trends of hemodynamic parameters following LVAD implantation. Methods and results: We retrospectively reviewed patients who underwent LVAD implantation between 4/2014 and 8/2018. We collected hemodynamic parameters from right heart catheterizations (RHCs). Among 199 consecutive patients, we enrolled 150 patients who had both pre- and post-implant RHCs. They had 3 (2, 4) post-implant RHCs during follow-up of 2.3 (1.3, 3.1) years. Mean age was 57±13 years and 102 patients (68%) were male. Following LVAD implantation, pulmonary arterial pressure and pulmonary capillary wedge pressure decreased and cardiac index increased significantly, and then remained unchanged throughout follow-up. Right atrial pressure (RAP) decreased initially, and then gradually increased to pre-implant values. Pulmonary artery pulsatility index (PAPI) decreased initially and returned to pre-implant values, and then progressively decreased over longer follow-up. Subgroup analysis showed significant differences in the trajectories of PAPI based on gender. Conclusions: Despite improvement in left-side filling pressures and cardiac index following LVAD implantation, RAP increased and PAPI decreased over time suggesting progressive right ventricular dysfunction.
... The question on suite is therefore: "Who can be a reasonable candidate to CARDIOmems adoption?" Today, an acceptable answer could be "Patients that despite appropriate effort in controlling congestion still retain evidence of intravascular fluid overload at time of hospital discharge, i.e., those with enlarged cava vein with limited respiratory variations (detected with abdominal echography) [31], and/or inadequate response to loop diuretic therapy as expressed by a decreased urinary sodium excretion (e.g., cumulative 24 h sodium output of < 100 mmol after optimized diuretic dose) [32]. In subjects with such limited renal excretive power, the chances of new HF exacerbations are very high, and timely modulation of HF drugs could avoid both over and under treatment, allowing effective outcome improvement. ...
Article
Full-text available
The burden of hospitalizations driven by exacerbation of acute heart failure remains unacceptably high. The associated use of hospital resources drives increasing patient, caregiver, and economic costs. Noninvasive telemedical systems investigated in randomized controlled trials have failed to demonstrate to reduce hospitalization rates probably because of the indirect (non-linear) relationship of the measured biological signals with the patient congestion status. Instead, there is increasing evidence that direct measure of intracardiac and pulmonary artery pressure can effectively guide heart failure management and reduce hospitalizations. Early studies adopting implantable hemodynamic monitors in the right heart unveiled the potential of pressure-based heart failure management, whereas subsequent investigations showed the powerful preemptive approach for heart failure exacerbations. One large randomized trial (CHAMPION) proved that a direct pulmonary pressure monitor system (CardioMEMS) substantially reduced heart failure hospitalizations in subjects randomized to active pulmonary pressure-guided management. The system monitoring safety and efficacy were also excellent. The study proved that early management in response to increased pulmonary pressure is able to provide the most effective therapeutic intervention to prevent heart failure exacerbations.
... Right ventricular dysfunction (RVD) predicts worse clinical outcomes, including death, in heart failure (HF) (1)(2)(3)(4)(5)(6) and pulmonary hypertension (PH) patients (7)(8)(9), irrespective of etiology, left ventricular function, or pulmonary artery pressures. Although RVD is largely a consequence of pulmonary hypertension, left heart disease is the most common etiology of PH, and HF patients with RVD outnumber other PH patients with RVD. ...
Article
Right ventricular dysfunction is highly prevalent across cardiopulmonary diseases and independently predicts death in both heart failure (HF) and pulmonary hypertension (PH). Progression towards right ventricular failure (RVF) can occur in spite of optimal medical treatment of HF or PH, highlighting current insufficient understanding of RVF molecular pathophysiology. To identify molecular mechanisms that may distinctly underlie RVF, we investigated the cardiac ventricular transcriptome of advanced HF patients, with and without RVF. Using an integrated systems genomic and functional biology approach, we identified an RVF-specific gene module, for which WIPI1 served as a hub and HSPB6 and MAP4 as drivers, and confirmed the ventricular specificity of Wipi1, Hspb6, and Map4 transcriptional changes in adult murine models of pressure overload induced RV- versus LV- failure. We uncovered a shift towards non-canonical autophagy in the failing RV that correlated with RV-specific Wipi1 upregulation. In vitro siRNA silencing of Wipi1 in neonatal rat ventricular myocytes limited non-canonical autophagy and blunted aldosterone-induced mitochondrial superoxide levels. Our findings suggest that Wipi1 regulates mitochondrial oxidative signaling and non-canonical autophagy in cardiac myocytes. Together with our human transcriptomic analysis and corroborating studies in an RVF mouse model, these data render Wipi1 a potential target for RV-directed HF therapy.
... The Frank-Starling mechanism identifies preload as a major determinant of cardiac output and further suggests that reducing volume overload may improve cardiac output, or at least not diminish cardiac output, among patients with systolic heart failure in a volumeoverloaded state. 2 More recent data suggests that elevated cardiac filling pressures are associated with poor short-and long-term outcomes among patients with heart failure. [3][4][5] Current approaches to reduce cardiac preload focus on diuretic therapy and vasodilators. 6 Devicebased approaches for decongestion of patients with acute heart failure include aquapheresis, hemodialysis, and investigational approaches such as impeller pumps in the descending aorta. ...
Article
Background Acutely decompensated heart failure remains a major clinical problem. Volume overload promotes cardiac and renal dysfunction and is associated with increased morbidity and mortality in heart failure. We hypothesized that transient occlusion of the superior vena cava (SVC) will reduce cardiac filling pressures without reducing cardiac output or systemic blood pressure. The objective of this proof of concept study was to provide initial evidence of safety and feasibility of transient SVC occlusion in patients with acutely decompensated heart failure and reduced ejection fraction. Methods and Results In eight patients with systolic heart failure, SVC occlusion was performed using a commercially available occlusion balloon. Five minutes of SVC occlusion reduced biventricular filling pressures without decreasing systemic blood pressure or total cardiac output. In three of the eight patients, a second 10‐minutes occlusion had similar hemodynamic effects. SVC occlusion was well‐tolerated without development of new symptoms, new neurologic deficits, or any adverse events including stroke, heart attack, or reported SVC injury or thrombosis at 7 days of follow up. Conclusion We report the first clinical experience with transient SVC occlusion as a potentially new therapeutic approach to rapidly reduce cardiac filling pressures in heart failure. No prohibitive safety signal was identified and further testing to establish the clinical utility of transient SVC occlusion for acute decompensated heart failure is justified.
... 5 These highly associated variables included in the logistic regression could have affected the significance of the CVP/PCWP ratio. In HT candidates, several studies have shown that an increased CVP/ PCWP ratio is associated with impaired renal function prior to the transplant; nevertheless, these studies did not explore its association with AKI after HT. 36,37 Preoperative eGFR was not found to be an independent predictor of severe AKI after HT in the present study, and the authors found that the early development of AKI after HT largely was influenced by perioperative hemodynamics as opposed to preoperative renal function. In patients whose preoperative renal impairment is primarily hemodynamic in origin (ie, cardiorenal syndrome), renal function improves with restoration of adequate RV and LV output. ...
Article
Introduction Acute kidney injury (AKI) after heart transplantation (HT) is a common complication, which can lead to subsequent chronic kidney disease, end-stage kidney disease requiring dialysis and higher risk of cardiovascular events post HT.¹ The aim of the study is to determine the perioperative predictors of severe AKI after HT. The authors hypothesized that relative pulmonary hypertension (PH), defined by a ratio that relates mean arterial-to-mean pulmonary arterial pressure (MAP/MPAP) is a risk factor independently associated to post-HT severe AKI. Methods After obtaining Institutional Review Board approval, the authors retrospectively studied all consecutive adult patients who underwent HT between January 2009 and December 2017 at a tertiary care university hospital and followed-up with them until December 2019. Follow-up was accomplished for all patients. Patients included in the analysis had undergone first orthotopic HT and were 18 years or older. Patients who underwent an additional organ transplantation (kidney, liver, lung) before or concurrently with HT, and those who died within 24 hours after HT were excluded. According to KDIGO classification,² patients were divided into 2 groups based on AKI severity developed within 7 days after HT: patients with severe AKI (stage 3) and patients with minor or non-AKI. P values < 0.05 were considered to be statistically significant. Results During the study period, a total of 205 adult patients underwent HT. Patients who underwent previous heart (n=3) or kidney transplantation (n=1), combined transplantation (n=13, including 2 heart re-transplantations) or died within 24 hours after HT (n=6) were excluded. A total 184 patients met the inclusion criteria. Among the included patients, 83.2% (n=153) suffered from AKI, including 40.8% (n=75) AKI stage 1, 19.6% (n=36) AKI stage 2 and 22.8% (n=42) AKI stage 3. Twenty-nine patients (15.8%) required RRT in the postoperative period. Using multivariate logistic regression analysis, the independent risk factors related to AKI stage 3 after HT were preoperative relative PH (OR:1.62, 95% CI:1.05-2.49, p=0.028), central venous-to-pulmonary capillary wedge pressure ratio >= 0.86 (OR:3.59, 95% CI:1.13-11.43, p=0.030) and postoperative right ventricular dysfunction (OR:3.63, 95% CI:1.50-8.75, p=0.004). Conversely, preoperative estimated glomerular filtration rate (OR:0.99, 95% CI:0.97-1.00, p=0.143) was not related to AKI stage 3 after HT. Discussion In patients undergoing heart transplantation, severe AKI was more likely related to preoperative relative PH, central venous-to-pulmonary capillary wedge pressure ratio and postoperative RV failure than to preoperative estimated glomerular filtration rate. Early recognition of perioperative AKI risk factors in the HT setting may provide possibilities of prevention and treatment strategies.
... We did not find a significant correlation between PASP and BUN but these were the only two parameters that were predictive for readmission among this study population. However, the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial showed that increasing right arterial pressure(RAP)/pulmonary capillary wedge pressure(PCWP) was associated with the elevated in-hospital BUN, discharge BUN and creatinine (P≤0.005 for all) [22]. It is also important to note that the ESCAPE trial, involved patients with advanced HF, most of whom had elevated PCWPs and the increasing RAP/PCWP ratio resulted from increasing RAP. ...
... The ratio between right atrial pressure and PAWP was used as a haemodynamic surrogate of RV dysfunction [30]. ...
Article
Full-text available
Background In pulmonary hypertension (PH), both wedge pressure elevation (PAWP) and a precapillary component may affect right ventricular (RV) afterload. These changes may contribute to RV failure and prognosis. We aimed at describing the different haemodynamic phenotypes of patients with PH due to left heart disease (LHD) and at characterizing the impact of pulmonary haemodynamics on RV function and outcome PH-LHD. Methods Patients with PH-LHD were compared with treatment-naïve idiopathic/heritable pulmonary arterial hypertension (PAH, n = 35). PH-LHD patients were subdivided in Isolated post-capillary PH (IpcPH: diastolic pressure gradient, DPG<7 mmHg and pulmonary vascular resistance, PVR≤3 WU, n = 37), Combined post- and pre-capillary PH (CpcPH: DPG≥7 mmHg and PVR>3 WU, n = 27), and “intermediate” PH-LHD (either DPG <7 mmHg or PVR ≤3 WU, n = 29). Results Despite similar PAWP and cardiac index, haemodynamic severity and prevalence of RV dysfunction increased from IpcPH, to “intermediate” and CpcPH. PVR and DPG (but not compliance, Ca) were linearly correlated with RV dysfunction. CpcPH had worse prognosis (p<0.05) than IpcPH and PAH, but similar to “intermediate” patients. Only NTproBNP and Ca independently predicted survival in PH-LHD. Conclusions In PH-LHD, haemodynamic characterization according to DPG and PVR provides important information on disease severity, predisposition to RV failure and prognosis. Patients presenting the CpcPH phenotype appear to have haemodynamic profile closer to PAH but with worse prognosis. In PH-LHD, Ca and NTproBNP were independent predictors of survival.
... E A has recently been shown to predict outcomes better than PVR and other markers of load (transpulmonary gradient and diastolic pulmonary gradient) in three separate heart failure cohorts [ 16]. To evaluate RV adaptation, the ratio of RAP:PAWP was calculated which has been validated as a meaningful measure of RV adaptation in prior studies [3,17,18]. ...
Article
Full-text available
Both operative and hemodynamic mechanisms have been implicated in right heart failure (RHF) following surgical left ventricular assist device (LVAD) implantation. We investigated the effects of percutaneous LVAD (pLVAD; Impella®, Abiomed) support on right ventricular (RV) load and adaptation. We reviewed all patients receiving a pLVAD for cardiogenic shock at our institution between July 2014 and April 2017, including only those with pre- and post-pLVAD invasive hemodynamic measurements. Hemodynamic data was recorded immediately prior to pLVAD implantation and up to 96 h post-implantation. Twenty-five patients were included. Cardiac output increased progressively during pLVAD support. PAWP improved early post-pLVAD but did not further improve during continued support. Markers of RV adaptation (right ventricular stroke work index, right atrial pressure (RAP), and RAP to pulmonary artery wedge pressure ratio (RAP:PAWP)) were unchanged acutely implant but progressively improved during continued pLVAD support. Total RV load (pulmonary effective arterial elastance; EA) and resistive RV load (pulmonary vascular resistance; PVR) both declined progressively. The relationship between RV load and RV adaptation (EA/RAP and EA/RAP:PAWP) was constant throughout. Median vasoactive-inotrope score declined after pLVAD placement and continued to decline throughout support. Percutaneous LVAD support in patients with cardiogenic shock did not acutely worsen RV adaptation, in contrast to previously described hemodynamic effects of surgically implanted durable LVADs. Further, RV load progressively declined during support, and the noted RV adaptation improvement was load-dependent as depicted by constant EA/RA and EA/RAP:PAWP relationships. These findings further implicate the operative changes associated with surgical LVAD implantation in early RHF following durable LVAD.
... 6,20 Right heart catheterization, the standard in hemodynamic monitoring after HTx, provides mRAP, mPAP, and mPCWP, which are indicators not only of left-and right-sided allograft function and pulmonary vascular pressure and resistance, but also of the systemic hemodynamic state. 21,22 Mean pressures in the right atrium and mPCWP mainly reflect right and left heart function, while elevated LV filling pressure can be estimated by mPCWP. 23 Right heart pressures change significantly in the first months after HTx as the allograft and the vasculature of the host adjust to the posttransplant condition. ...
Article
Full-text available
Background This proof-of-concept study investigated the feasibility of using biomarkers to monitor right heart pressures (RHP) in heart transplanted (HTx) patients. Methods In 298 patients, we measured 7.6 years post-HTx mean pressures in the right atrium (mRAP) and pulmonary artery (mPAP) and capillaries (mPCWP) along with plasma high-sensitivity troponin T (hsTnT), a marker of cardiomyocyte injury, and the multidimensional urinary classifiers HF1 and HF2, mainly consisting of dysregulated collagen fragments. Results In multivariable models, mRAP and mPAP increased with hsTnT (per 1-SD, +0.91 and +1.26 mm Hg; P < 0.0001) and with HF2 (+0.42 and +0.62 mm Hg; P ≤ 0.035), but not with HF1. mPCWP increased with hsTnT (+1.16 mm Hg; P < 0.0001), but not with HF1 or HF2. The adjusted odds ratios for having elevated RHP (mRAP, mPAP or mPCWP ≥10, ≥24, ≥17 mm Hg, respectively) were 1.99 for hsTnT and 1.56 for HF2 (P ≤ 0.005). In detecting elevated RHPs, areas under the curve were similar for hsTnT and HF2 (0.63 vs 0.65; P = 0.66). Adding hsTnT continuous or per threshold or HF2 continuous to a basic model including all covariables did not increase diagnostic accuracy (P ≥ 0.11), whereas adding HF2 per optimized threshold increased both the integrated discrimination (+1.92%; P = 0.023) and net reclassification (+30.3%; P = 0.010) improvement. Conclusions Correlating RHPs with noninvasive biomarkers in HTx patients is feasible. However, further refinement and validation of such biomarkers is required before their clinical application can be considered.
... Do różnicowania nadciśnienia płucnego związanego z chorobami lewego serca konieczne jest uzyskanie dobrej jakości zapisu PAWP. W rzadkich przypadkach może zaistnieć potrzeba cewnikowania lewego serca w celu uzyskania bezpośrednich LVEDP [21]. ...
... The CVP versus PAWP relationship may be appreciated to assess right ventricular function and pericardial constraint indirectly (Figure 4). [70][71][72] With increasing pericardial restraint and enhanced ventricular interdependence, which often accompanies right-sided HF, CVP may be disproportionately high and make an important contribution to elevated left-sided filling pressure. 73 This is because CVP approximates pericardial pressure and can therefore be taken as an estimate of the extramural pressure applied to the left heart. ...
Article
Heart failure is characterized by pathologic hemodynamic derangements, including elevated cardiac filling pressures ("backward" failure), which may or may not coexist with reduced cardiac output ("forward" failure). Even when normal during unstressed conditions such as rest, hemodynamics classically become abnormal during stressors such as exercise in patients with heart failure. This has important upstream and downstream effects on multiple organ systems, particularly with respect to the lungs and kidneys. Hemodynamic abnormalities in heart failure are affected by processes that extend well beyond the cardiac myocyte, including important roles for pericardial constraint, ventricular interaction, and altered venous capacity. Hemodynamic perturbations have widespread effects across multiple heart failure phenotypes, ranging from reduced to preserved ejection fraction, acute to chronic disease, and cardiogenic shock to preserved perfusion states. In the lung, hemodynamic derangements lead to the development of abnormalities in ventilatory control and efficiency, pulmonary congestion, capillary stress failure, and eventually pulmonary vascular disease. In the kidney, hemodynamic perturbations lead to sodium and water retention and worsening renal function. Improved understanding of the mechanisms by which altered hemodynamics in heart failure affect the lungs and kidneys is needed in order to design novel strategies to improve clinical outcomes.
... One of the highest imprecisions in the prediction of hemodynamic measures by echocardiography is observed in the assessment of right atrial pressure (RAP) [17][18][19][20]. The knowledge of RAP is clinically relevant, since it may help to stratify prognosis in both patients with heart failure [21,22] and pulmonary hypertension [8,23], and it is vital to optimize fluid management (loading and unloading) in several clinical scenarios [24]. RAP is currently calculated by measuring inferior vena cava (IVC) dimension and collapsibility during respiration (indicated as caval index or collapsibility index) [7]. ...
Article
Full-text available
The non-invasive estimation of right atrial pressure (RAP) would be a key advancement in several clinical scenarios, in which the knowledge of central venous filling pressure is vital for patients’ management. The echocardiographic estimation of RAP proposed by Guidelines, based on inferior vena cava (IVC) size and respirophasic collapsibility, is exposed to operator and patient dependent variability. We propose novel methods, based on semi-automated edge-tracking of IVC size and cardiac collapsibility (cardiac caval index—CCI), tested in a monocentric retrospective cohort of patients undergoing echocardiography and right heart catheterization (RHC) within 24 h in condition of clinical and therapeutic stability (170 patients, age 64 ± 14, male 45%, with pulmonary arterial hypertension, heart failure, valvular heart disease, dyspnea, or other pathologies). IVC size and CCI were integrated with other standard echocardiographic features, selected by backward feature selection and included in a linear model (LM) and a support vector machine (SVM), which were cross-validated. Three RAP classes (low < 5 mmHg, intermediate 5–10 mmHg and high > 10 mmHg) were generated and RHC values used as comparator. LM and SVM showed a higher accuracy than Guidelines (63%, 71%, and 61% for LM, SVM, and Guidelines, respectively), promoting the integration of IVC and echocardiographic features for an improved non-invasive estimation of RAP.
... Transthoracic echocardiography (TTE) and a right heart catheter (RHC) study were performed preoperatively in all patients, and postoperative TTE was performed at 54.6 ± 26.7 days and an RHC study at 31.8 ± 9.1 days after LVAD implantation. In the RHC study, the right atrial pressure to pulmonary capillary wedge pressure ratio was calculated as an indicator of right ventricular dysfunction [12]. ...
Article
Full-text available
Objectives: Limited data are available for use of the HeartMate 3 (HM 3) left ventricular assist device in patients with a small body surface area (BSA). Because the HM 3 is currently the sole device available worldwide, we conducted a single-centre retrospective study of patients with a small BSA (<1.5 m2) who underwent HM 3 implantation to better understand the operative and postoperative management. Methods: This study enrolled 64 consecutive patients who had undergone HM 3 implantation from August 2018 to July 2021. The patients were divided into 2 groups based on their BSA before the operation: BSA of <1.5 m2 (small BSA group, n = 18) and BSA of ≥1.5 m2 (regular BSA group, n = 46). The primary study endpoint was survival free of events such as disabling stroke and pump failure. The secondary endpoint was the frequency of adverse events. Results: The average BSA was 1.38 m2 in the small BSA group. The overall event-free survival rate at 12 months was 100% and 86.7% in the small BSA group and regular BSA group, respectively, and no significant difference was found between the 2 groups (log-rank P = 0.2). The number of cumulative adverse events of death, stroke of any severity, driveline infection, pump infection, ventricular arrhythmia, gastrointestinal Haemorrhage and pump failure was similar between the 2 groups. Conclusions: The HM 3 was safely implanted in patients with a small BSA, and postoperative outcomes were acceptable regardless of BSA. However, further research is needed to confirm the indications for HM 3 implantation in even smaller patients.
... Prior studies have indicated that a reduced RVSWI is an independent predictor for biventricular support requirement in patient undergoing LVAD placement 7 and that an increased RA:PCWP ratio is associated with reduced RV function and adverse outcomes in advanced heart failure. 8 Given these previous data, combined with hemodynamic findings and minimal clinical improvement, we determined that RV support, in addition to LV support, was necessary to allow for treatment of his underlying disorder. Prior evidence indicates that biventricular impella (Bi-Pella) is a feasible approach that improves cardiac output and may be associated with improved outcomes in patients with biventricular failure. ...
Article
Full-text available
The use of biventricular impella support in patients with acute, reversible causes of biventricular cardiogenic shock may play a role in shortening the time to recovery and preventing significant negative outcomes such as renal or hepatic failure. The use of biventricular impella support in patients with acute, reversible causes of biventricular cardiogenic shock may play a role in shortening the time to recovery and preventing significant negative outcomes such as renal or hepatic failure.
... However, direct LAP monitoring may have distinct advantages, in comparison to PAP monitoring. In patients with advanced heart failure, left-and right-sided filling pressures have frequently been found to be mismatched 5,6 . PAP also fails to correlate with left ventricular filling pressure (LVEDP) in a variety of conditions, such as in patients with acute heart failure 7,8 . ...
Article
Full-text available
Objective Patients with heart failure (HF) are at an increased risk of hospital admissions. The aim of this report is to describe the feasibility, safety and accuracy of a novel wireless left atrial pressure (LAP) monitoring system in HF patients. Methods The V-LAP Left Atrium Monitoring systEm for Patients With Chronic sysTOlic & Diastolic Congestive heart Failure (VECTOR-HF) study is a prospective, multicenter, single-arm, open-label, first-in human clinical trial to assess the safety, performance and usability of the V-LAP system (Vectorious Medical Technologies, Ltd) in NYHA Class III HF patients. The device was implanted in the inter-atrial septum via a percutaneous, trans-septal approach, guided by fluoroscopy and echocardiography. Primary endpoints included the successful deployment of the implant, ability to perform initial pressure measurements and safety outcomes. Results To date, 24 patients were implanted with the LAP monitoring device. No device-related complications have occurred. LAP was reported accurately, agreeing well with wedge pressure at 3 months (Lin's CCC=0.850). After 6 months, NYHA class improved in 40% of the patients (95% CI =16.4%-63.5%), while 6-minute walk test distance had not changed significantly (313.9 ± 144.9 vs. 232.5 ± 129.9 meters, p=0.076). Conclusion The V-LAP left atrium monitoring system appears to be safe and accurate.
... For example, a study of 657 consecutive heart transplant recipients in Italy from 2000-2018 found that right heart failure (RHF) defined by low PAPI (<1.68) was associated with the need for renal replacement therapy and primary graft dysfunction [24]. For both LVAD and transplant patients, in an analysis of the previously described ESCAPE trial, the authors found that an increased RAP/PCWP ratio was associated with adverse clinical outcomes [25]. ...
Article
Patients with chronic congestive heart failure belong to a population with reduced quality of life, poor functional class, and increased risk of mortality and morbidity. In these patients, assessment of invasive hemodynamics both serves therapeutic purposes and is useful for stratification roles. The right heart catheterization has become a cornerstone diagnostic tool for patients in refractory heart failure or cardiogenic shock, as well as for the assessment of candidacy for heart replacement therapies, and the management of patients following mechanical circulatory assist device implantation and heart transplantation.
Chapter
Increased body fluid volume portends poorer outcomes in both acute and chronic heart failure. Inadequate decongestion, defined as absence of hemoconcentration or increases in serum creatinine, is consistently associated with higher rates of heart failure hospitalizations and cardiovascular mortality. However, available means to identify and quantify abnormal fluid volume, monitor changes during decongestive therapies and determine when an optimal fluid volume has been achieved are poorly understood. In addition, ideal methods to assess extracellular and intracellular fluid status remain elusive. These knowledge gaps lead to unacceptably poor heart failure outcomes, as underscored by the results of many acute heart failure trials in which, regardless of decongestive therapy, only a small minority of patients achieve optimal volume status. The intent of this discussion is to describe methods for the assessment of fluid volume status, compare their relative advantages and limitations and propose research priorities in this area.
Article
Despite increasing prevalence in critical care units, cardiogenic shock related to HF (HF-CS) is incompletely understood and distinct from acute myocardial infarction related CS. This review highlights the pathophysiology, evaluation, and contemporary management of HF-CS.
Article
Background: Previous studies have shown that pulmonary hypertension is a predictor of mortality in patients with systolic heart failure (SHF). Persistent pulmonary hypertension after a reactivity test is associated with a worse outcome after transplantation. Recent studies have shown the utility of different haemodynamic parameters. Aims: To define best haemodynamic parameters for risk stratification in patients with advanced systolic heart failure. Methods: We included 425 consecutive patients who underwent a right heart catheterization with an inotropic challenge if indicated. Results: During a median (interquartile range) follow-up of 1.67 (0.49–4.49) years, there were 151 major cardiac events (126 cardiovascular deaths and 25 post-operative deaths after ventricular assist device implantation or heart transplantation). The most powerful independent predictors of major cardiac events were baseline right atrial pressure (RAP) (hazard ratio [HR] 1.09, 95% confidence interval [CI] 1.06–1.12; P < 0.0001) and baseline pulmonary vascular resistance (PVR) (HR 1.10; 95% CI 1.03–1.17; P = 0.002]). After inotropic challenge, the only independent predictor was mean pulmonary arterial pressure (mPAP) (HR 1.06; 95% CI 1.03–1.09; P < 0.0001). The combination of PVR (≤ or > 3 Wood units), RAP (< or ≥ 9 mmHg) and mPAP after the inotropic challenge (≤ or > 30 mmHg) was the best predictor of major events. Conclusion: We suggest using a simple algorithm based on baseline PVR, baseline RAP and mPAP after the inotropic challenge for the risk stratification of stable patients with advanced systolic heart failure.
Article
An interaction between the intestine and cardiovascular disease has been suggested. We thought to clarify the association between intestinal conditions and clinical outcomes in patients with heart failure (HF). Hemodynamic parameters in intestinal vessels [superior mesenteric artery (SMA), inferior mesenteric artery (IMA), and portal vein (PV)] and average colon wall thickness (aCWT) from the ascending colon to sigmoid colon were evaluated in 224 hospitalized HF patients. Echocardiographic parameters and composite event rates (all-cause mortality, readmission for HF deterioration, major ventricular arrhythmias) were also examined. Higher PV congestion index (CI) and aCWT were observed in patients with New York Heart Association (NYHA) class III/IV. Higher PVCI [hazard ratio (HR) per + 1 standard deviation (SD) 1.50, p < 0.01] and aCWT (HR per + 1 SD 1.45, p < 0.01) were independently associated with higher composite event rates during the follow-up of 122 ± 68 days. None of SMA/IMA hemodynamic parameters were associated with NYHA class or composite event rates. Higher right ventricular end-diastolic dimension (38 ± 7 vs 34 ± 9 mm, p < 0.01) and lower tricuspid annual plane systolic excursion (15 ± 5 vs 19 ± 5 mm, p < 0.001) were observed in patients with higher PVCI (> 0.031 cm s) and aCWT (> 2.8 mm) relative to those in others. In conclusion, increased portal congestion and intestinal edema were associated with severe HF symptoms and poor outcomes in hospitalized HF patients, in addition to being associated with impaired right-sided cardiac function.
Article
Full-text available
Background: Outcomes in peripartum cardiomyopathy (PPCM) vary. We sought to determine whether severity of left or right ventricular dysfunction (RVD) at PPCM diagnosis differentially associates with adverse outcomes. Methods and results: We conducted a single-center retrospective cohort study of 53 patients with PPCM. The primary outcome was a composite of left ventricular assist device implantation, cardiac transplantation, or death. We used Kaplan-Meier curves to examine event-free survival and Cox proportional hazards models to examine associations of left ventricular (LV) ejection fraction <30%, LV end-diastolic diameter ≥60 mm, and moderate-to-severe RVD at PPCM diagnosis with the primary outcome. Median (interquartile range) follow-up time was 3.6 (1.4-7.3) years. Seventeen patients (32%) experienced the primary outcome, of whom 11 had moderate-to-severe RVD at time of PPCM diagnosis. Overall event-free survival differed by initial RVD severity and LV ejection fraction <30%, but not by LV end-diastolic diameter ≥60 mm. In univariable analyses, LV ejection fraction <30% and moderate-to-severe RVD were associated with the outcome (hazard ratios [95% confidence intervals] of 4.85 [1.11-21.3] and 4.26 [1.47-11.6], respectively). In a multivariable model with LV ejection fraction <30%, LV end-diastolic diameter ≥60 mm, and moderate-to-severe RVD, only moderate-to-severe RVD was independently associated with the outcome (hazard ratio [95% confidence interval], 3.21 [1.13-9.10]). Although most outcomes occurred within the first year, nearly a third occurred years after PPCM diagnosis. Conclusions: Initial moderate-to-severe RVD is associated with a more advanced cardiomyopathy phenotype and increased risk of adverse outcomes in PPCM, within and beyond the first year of diagnosis. By identifying a worse PPCM phenotype, initial moderate-to-severe RVD may prompt earlier consideration of advanced heart replacement therapies.
Article
Despite advances in biomarkers and technology, the clinical examination (i.e., a history and physical examination) remains central in the management of patients with heart failure. Specifically, the clinical examination allows noninvasive assessment of the patient's underlying hemodynamic state, based on whether the patient has elevated ventricular filling pressures and/or an inadequate cardiac index. Such assessments provide important prognostic information and help guide therapeutic decision-making. Herein, we critically assess the utility of the clinical examination for these purposes and provide practical tips we have gleaned from our practice in the field of advanced heart failure. We note that the ability to assess for congestion is superior to that for inadequate perfusion. Furthermore, in current practice, elevated left ventricular filling pressures are inferred by findings related to an elevated right atrial pressure. We discuss an emerging classification system from the clinical examination that categorizes patients based on whether elevation of ventricular filling pressures occurs on the right side, left side, or both sides.
Chapter
Understanding heart failure, left ventricular assist devices (LVAD), and the associated cardiorenal syndrome requires an understanding of cardiovascular hemodynamics. This chapter explores the assessment of cardiovascular hemodynamics and how this assessment can be used to guide management. Special attention is given to the assessment and management of advanced heart failure and left ventricular assist devices.
Article
Background: Pulmonary hypertension is not uncommon in patients with renal disease and vice versa; therefore, it influences treatments and outcomes. There is a large body of literature on pulmonary hypertension in patients with kidney disease, its prognostic implications, economic burden, and management strategies. However, the converse, namely the hemodynamic effects of pulmonary hypertension on kidney function (acute and chronic kidney injury) is less studied and described. There is also increasing interest in the effects of pulmonary hypertension on kidney transplant outcomes. The relationship is a complex phenomenon and multiple body systems and mechanisms are involved in its pathophysiology. Although the definition of pulmonary hypertension has evolved over time with the understanding of multiple interplays between the heart, lungs, kidneys, etc; there is limited evidence to provide a specific treatment strategy when kidneys and lungs are affected at the same time. Nevertheless, available evidence appears to support new therapeutics and highlights the importance of individualized approach. There is sufficient research showing that the morbidity and mortality from PH are driven by the influence of the pulmonary hemodynamic dysfunction on the kidneys. Conclusion: This concise review focuses on the effects of pulmonary hypertension on the kidneys, including, the patho-physiological effects of pulmonary hypertension on acute kidney injury, progression of CKD, effects on kidney transplant outcomes, progression of kidney disease in situations such as post LVAD implantation and novel diagnostic indices. We believe a review of this nature will fill in an important gap in understanding the prognostic implication of pulmonary hypertension on renal disease, and help highlight this important component of the cardio-reno-pulmonary axis.
Article
Heart failure (HF) is associated with considerable morbidity and mortality. The increasing prevalence of HF and inpatient HF hospitalization has a considerable burden on healthcare cost and utilization. The recognition that hemodynamic changes in pulmonary artery pressure (PAP) and left atrial pressure precede the signs and symptoms of HF has led to interest in hemodynamic guided HF therapy as an approach to allow earlier intervention during a heart failure decompensation. Remote patient monitoring (RPM) utilizing telecommunication, cardiac implantable electronic device parameters and implantable hemodynamic monitors (IHM) have largely failed to demonstrate favorable outcomes in multicenter trials. However, one positive randomized clinical trial testing the CardioMEMS device (followed by Food and Drug Administration approval) has generated renewed interest in PAP monitoring in the HF population to decrease hospitalization and improve quality of life. The COVID-19 pandemic has also stirred a resurgence in the utilization of telehealth to which RPM using IHM may be complementary. The cost effectiveness of these monitors continues to be a matter of debate. Future iterations of devices aim to be smaller, less burdensome for the patient, less dependent on patient compliance, and less cumbersome for health care providers with the integration of artificial intelligence coupled with sophisticated data management and interpretation tools. Currently, use of IHM may be considered in advanced heart failure patients with the support of structured programs.
Article
Patients with pulmonary atresia and intact ventricular septum (PA-IVS) require intervention early in life, and most survive to a definitive procedure of either Fontan circulation or right ventricle to pulmonary artery (RV-PA) repair. It remains unknown how surgical strategy impacts hemodynamics and comorbidities in adults. Retrospective analysis of adults (age ≥18 years) with PA-IVS undergoing hemodynamic catheterization at Mayo Clinic, MN between January 2000 through January 2020 was performed. Fourteen patients in the RV-PA group (71% biventricular, 29% 1.5 ventricle repair) and 19 post-Fontan patients [9 lateral tunnel (48%), 6 atriopulmonary (32%), and 4 extracardiac (21%)] were identified. Median age was 29 (21, 34) years. There were no differences in demographics and laboratory data (including MELD-XI) between groups. All patients assessed for liver disease had evidence of hepatic congestion or cirrhosis (14 in the Fontan group and 4 in the RV-PA group). Invasive hemodynamics were comparable between groups with the Fontan and RV-PA groups having similar systemic venous pressure (15.7±4.4 vs. 14.3±6.2, p=0.44) and cardiac output (2.2±0.6 vs. 2.0±0.4 L/min/m2, p=0.23). There was no difference in transplant-free survival (p=0.92; 5-year transplant-free survival RV-PA 84%, Fontan 80%). Hemodynamic derangements, namely elevated systemic venous pressure and low cardiac output, are prevalent in patients with PA-IVS undergoing cardiac catheterization regardless of surgical strategy.
Article
Symptoms of heart failure (HF) are due in large part to elevation of left and/or right ventricular filling pressures. Although abnormal diastolic function is difficult to define, it contributes to the elevation of filling pressures. Tests that characterize aspects of diastolic function or structural changes associated with diastolic dysfunction, may help in establishing a diagnosis of HF, assessing prognosis, and guiding treatments. Individual echocardiographic parameters correlate weakly with LV (LV) filling pressures measured directly. However, a combination of multiple parameters improves accuracy for detection of elevated filling pressures. Serum natriuretic peptide levels are related to ventricular filling pressures and, when elevated, are a key diagnostic criterion for HF. Currently available evidence is not adequate to recommend serial echocardiographic studies or natriuretic peptide level measurements to assess changes in filling pressures or to guide HF therapy. Measurements of inferior vena cava size and dynamics have potential for identifying inadequate decongestion during episodes of acute decompensated HF but have not yet demonstrated utility in improving HF outcomes. Direct measurement of LV filling pressures using implanted pressure sensors is the only "diastolic assessment" thus far that has proven efficacy in reducing HF hospitalization rates.
Article
Right heart catheterization is an established cornerstone of advanced heart failure management, as a clear understanding of the patient's hemodynamic status offers insight into diagnosis, prognosis, and management. In this review, the authors will describe the role of right heart catheterization in the diagnosis and management of shock, in the context of left ventricular assist devices, in the assessment of heart transplant candidacy, and also explore future directions of implantable monitoring devices for pulmonary artery and left atrial pressure monitoring.
Chapter
The impact of chronic heart disease leading to long term effects in the kidney is known as cardiorenal syndrome type 2 (CRS2). The combination of dysfunction in these two organs is notorious for its significant morbidity. The pathophysiology of CRS2 due to chronic heart failure with reduced ejection fraction (HFrEF) involves hemodynamic factors such as decrease in cardiac output and increase in venous congestion, neurohormonal activation and chronic inflammation while in heart failure with preserved ejection fraction (HFpEF) the hallmark of this condition is an increase in right and left sided heart filling pressures, compromised cardiac filling and consequent inadequate stroke volume reserve. Regardless of the initial trigger, fibrosis appears to be the common aftermath of the chronic inflammatory milieu of cardiorenal syndrome.
Article
Background: Historically, invasive hemodynamic guidance was not superior compared to clinical assessment in patients admitted with acute decompensated heart failure (ADHF). This study assessed the accuracy of clinical assessment vs invasive hemodynamics in patients with ADHF. Methods and results: We conducted a prospective cohort study of patients admitted with ADHF. Prior to right-heart catheterization (RHC), physicians categorically predicted right atrial pressure, pulmonary capillary wedge pressure, cardiac index and hemodynamic profile (wet/dry, warm/cold) based on physical examination and clinical data evaluation (warm = cardiac index > 2.2 L/min/m2; wet = pulmonary capillary wedge pressure > 18 mmHg). We collected 218 surveys (of 83 cardiology fellows, 55 attending cardiologists, 45 residents, 35 interns) evaluating 97 patients. Of those patients, 46% were receiving inotropes prior to RHC. The positive and negative predictive values of clinical assessment compared to RHC for the cold and wet subgroups were 74.7% and 50.4%. The accuracy of categorical prediction was 43.6% for right atrial pressure, 34.4% for pulmonary capillary wedge pressure and 49.1% for cardiac index, and accuracy did not differ by clinician (P > 0.05 for all). Interprovider agreement was 44.4%. Therapeutic changes following RHC occurred in 71.1% overall (P < 0.001). Conclusions: Clinical assessment of patients with advanced heart failure presenting with ADHF has low accuracy across all training levels, with exaggerated rates of misrecognition of the most high-risk patients.
Article
Hemodynamics play a central role in the pathophysiology of heart failure (HF), yet their proper assessment and optimization remains challenging. Heart failure is defined as the inability of the heart to deliver adequate perfusion (cardiac output) to the body at rest or exercise, or to require an elevation in cardiac filling pressures in order to do this. This bedrock definition is important because it relies on measurable quantities (filling pressures and output) that are readily assessed in the cardiac catheterization laboratory. Here we present three cases to illustrate how better understanding of the determinants of cardiac output and stroke volume: preload, afterload, contractility, and lusitropy, as well as the determinants of congestion (high filling pressures) may be used to guide optimization of hemodynamic status. The goal is that the readers will be able to think more critically when evaluating the hemodynamics of their patient in HF and recognize the complex interplay that determines the complex balance between cardiac ejection and filling capabilities, and how this alters symptoms and outcomes for patients with HF. Key Points • Careful assessment of hemodynamics in the catheterization laboratory allows for actionable insight to a patient's volume status, cardiac function and can help prognosticate outcomes. • Exercise hemodynamics in heart failure is a powerful tool to better understand the cause of symptoms and predict outcomes. • Clinicians should aim to decrease biventricular filling pressures to normal values to improve morbidity and reduce risk for readmission. • In patients with heart failure and reduced ejection fraction, clinicians should aim to decrease afterload as much as can be tolerated by the renal function and patient's symptoms. • Low cardiac output can often be improved by optimizing preload and afterload rather than initiating inotropes, which should be reserved until needed. • In advanced heart failure, the right heart function becomes a key determinant of symptoms and outcomes.
Article
Background : In approximately 25% of patients with heart failure and reduced left-ventricular ejection fraction (HFrEF), right-ventricular (RV) and left-ventricular (LV) filling pressures are discordant (i.e., one is elevated while the other is not). Whether clinical assessment allows detection of this discordance is unknown. We sought to determine the agreement of clinically- versus invasively-determined patterns of ventricular congestion. Methods : In 156 HFrEF subjects undergoing invasive hemodynamic assessment, we categorized patterns of ventricular congestion (no congestion, RV only, LV only, or both) based on clinical findings of RV (jugular venous distention, JVD) or LV (hepatojugular reflux, orthopnea, or bendopnea) congestion. Agreement between clinically and invasively determined [RV congestion if right atrial pressure (RAP) ≥10 mmHg and LV congestion if pulmonary capillary wedge pressure (PCWP) ≥22 mmHg)] categorizations was the primary endpoint. Results : The frequency of clinical patterns of congestion was: 51% no congestion, 24% both RV and LV, 21% LV only, and 4% RV only. JVD had excellent discrimination for elevated RAP (C=0.88). However, agreement between clinical and invasive congestion patterns was poor, λ=0.44 (95% CI 0.34-0.55). While those with no clinical congestion usually had low RAP and PCWP (67/79, 85%), over one-half (24/38, 64%) with isolated LV clinical congestion had PCWP <22 mmHg, most (5/7, 71%) with isolated RV clinical congestion had PCWP ≥22 mmHg, and ∼one-third (10/32, 31%) with both RV and LV clinical congestion had elevated RAP but PCWP <22 mmHg. Conclusions : While clinical examination allows accurate detection of elevated RAP, it does not allow accurate detection of discordant RV and LV filling pressures.
Article
The fibrosis-4 index (FIB-4 index) is a marker of liver fibrosis. It has been reported that the FIB-4 index in compensated phase is associated with estimated right-sided filling pressure and poor prognosis in patients with heart failure. However, the relationship with invasively obtained right-sided cardiac pressures has been unclear. Hemodynamic status was evaluated by right heart catheterization in 189 heart failure patients who were in a clinically compensated phase between January 2015 and September 2017. Patients were assigned to two groups based on a median FIB-4 index of 2.15, then hemodynamic parameters and event rates were compared. Endpoint was defined as a composite of all-cause death, readmission for heart failure, or left ventricular-assist device implantation. Then, we also investigated correlations between the FIB-4 index and clinical factors, including hemodynamic parameters. Patients with a high FIB-4 index were significantly older (76 [IQR, 63–80] vs. 65 [IQR, 56–74] years, P < 0.001) and had higher right atrial pressure (RAP; 7 [IQR, 5–11] vs. 4 [IQR, 1–6] mmHg, P < 0.001) and pulmonary capillary wedge pressure (16 [IQR, 12–22] vs. 12 [IQR, 8–19] mmHg, P = 0.011) than those with a low FIB-4 index. The FIB-4 index correlated more strongly with parameters of right-sided than left-sided HF (RAP, R = 0.41, P < 0.001; inferior vena cava diameter, R = 0.44, P < 0.001; pulmonary capillary wedge pressure, R = 0.15, P = 0.038; brain natriuretic peptide, R = 0.14, P = 0.29). Multiple regression analysis showed that the FIB-4 index independently correlated with RAP. In conclusion, the FIB-4 index can non-invasively reflect right-sided filling pressure, which might explain why it is associated with a poor prognosis, among patients with heart failure.
Article
Background: Right ventricular dysfunction (RVD) is a major issue in patients with advanced heart failure (HF) since it precludes the implantation of left ventricular assist device (LVAD) usually leaving heart transplantation (HTx) as the only available treatment option. Pulmonary artery pulsatility index (PAPi) is a hemodynamic parameter integrating information of right ventricular function and of pulmonary circulation. Our aim is to evaluate the association of pre-operative RVD, hemodynamically defined as a low PAPi, with post- HTx survival. Methods: Consecutive adult HTx recipient at two Italian transplant centers between 2000 and 2018 with available data on pre-HTx right heart catheterization were retrospectively included. RVD was defined as a value of PAPi lower than the 25th percentile of the study population. The association of RVD with 1-year post-HTx mortality and other secondary endpoint was evaluated. Multivariate logistic regression was used to adjust for clinical and hemodynamic variables. Analyses stratified by pulmonary vascular resistance (PVR) status (≥3 WU vs. <3 WU) were also performed. Results: Among 657 HTx recipients (female 31.1 %, age 53 ± 11 years), patients with pre-HTx RVD (PAPi <1.68) had significantly reduced 1-year survival (77.8% vs 87.1%, p=0.005), also after adjusting for estimated glomerular filtration rate, total bilirubin, PVR, serum sodium, inotropes, and mechanical circulatory support at HTx (hazard ratio [HR], 2.0; 95% confidence interval [CI], 1.3–3.1). RVD was also associated with post-HTx renal replacement therapy (HR 2.0 [1.05-3.3]) and primary graft dysfunction (PGD) (HR 1.7 [1.02-3.3]). When stratifying patients by estimated PVR status, RVD was associated with worse 1-year survival among patients with normal PVR (76.9 % vs. 88.3 % p= 0.003), but not in those with increased PVR (78.6 % vs. 83.2%, p= 0.49). Conclusions: Pre-operative RVD, evaluated through PAPi, is associated with mortality and morbidity after HTx, providing incremental prognostic value over traditional clinical and hemodynamic parameters.
Article
Secondary mitral regurgitation (MR) and heart failure are mutually dependent. Secondary MR occurs as a consequence of heart failure in patients with impaired left ventricular (LV) function, decreasing cardiac efficiency, accelerating a decline in contractility and worsening the already dismal prognosis of these patients. Advances in transcatheter techniques have now given promise to improved survival, outcomes, and quality of life for patients with advanced heart failure and secondary MR. Although transcatheter edge-to-edge repair is well established, transapical transcatheter mitral valve implantation (TMVI) may represent a more durable solution for correction of secondary MR without the need for cardiopulmonary bypass. Correction of MR, however, is thought to acutely increase LV afterload due to the elimination of low afterload regurgitant flow. In high-risk patients, this may cause acute decompensated heart failure. Off-pump TMVI on a beating heart poses a number of unique challenges, but also the opportunity to study invasive haemodynamic indices in high-risk heart failure patients for the first time. In the following discussion, we review the acute haemodynamic changes during off-pump TMVI in patients with heart failure in order to better guide optimal patient selection and management.
Chapter
Predominant right heart failure (RHF) is found in 5% of patients with myocardial infarction complicated by cardiogenic shock. The mortality rates of cardiogenic shock from RHF and left heart failure (LHF) are similar. The initial management of acute RHF should focus on the treatment of the underlying etiology, the correction of metabolic derangements, the maintenance of atrioventricular synchrony, and appropriate systemic perfusion and oxygenation. The hemodynamic parameters suggestive of RHF include elevated right atrial pressure (RAP), RAP: pulmonary capillary wedge pressure ratio (RAP/ PCWP) >0.86, and pulmonary artery pulsatility index (PAPi) <1. Percutaneous mechanical support options for acute RHF include Impella RP, TandemHeart Protek Duo, and Veno-Arterial Extracorporeal Membrane Oxygenation (VA-ECMO). The implantation of a contemporary durable left ventricular assist device (LVAD) in a right ventricle has been reported. The CentriMag right ventricular assist system can also be used as a bridge to recovery or transplant.
Chapter
Cardiovascular disease, especially heart failure, is common among patients with kidney disease, and vice versa. Acute or chronic dysfunction of the heart or kidneys triggers and sustains dysfunction of the other, through a combination of hemodynamic, neurohormonal, sympathetic nervous system and biochemical feedback mechanisms, among others. Hemodynamic changes such as increased afterload, venous congestion, hypervolemia, decreased cardiac contractility, low cardiac output, and impaired renal perfusion are commonly noted among patients with cardiorenal dysfunction and are shown to have varying degrees of prognostic relevance. The gold standard test for invasive assessment of cardiac hemodynamics is right heart catheterization using the pulmonary artery catheter. In this chapter, we discuss the evidence surrounding several invasive hemodynamic parameters in acute and chronic cardiorenal syndrome. We review pre and postcapillary mechanisms contributing to the development of pulmonary hypertension in chronic kidney disease and explore the role for invasive hemodynamic assessment for guiding treatment among those affected by heart failure and/or pulmonary hypertension within this population.
Article
Full-text available
Background When left ventricular (LV) filling pressure (FP) increases, the mitral valve (MV) opens early and precedes tricuspid valve (TV) opening in early diastole. We hypothesized that a visually-assessed time sequence of atrioventricular valves opening could become a new marker of elevated LVFP. We thus tested the diagnostic ability of a novel echocardiographic scoring system, visually-assessed time-difference between MV and TV opening (VMT) score, in heart failure (HF) patients. Methods We retrospectively analyzed 119 consecutive patients who underwent cardiac catheterization within 24 hours of echocardiography examination as a derivation cohort. In addition, a prospective study was conducted to validate the diagnostic ability of the VMT score in 50 patients. Elevated LVFP was defined as mean pulmonary arterial wedge pressure (PAWP) ≥15 mmHg. Time sequence of atrioventricular valves opening was visually assessed and scored (0, TV first; 1, simultaneous; 2, MV first). When the inferior vena cava was dilated, 1 point was added and VMT score was finally graded as 0–3. Cardiac events were recorded for 1 year after echocardiography. Results In the derivation cohort, PAWP was elevated in the higher VMT scores (0, 10±5; 1, 12±4; 2, 22±8; 3, 28±4 mmHg; ANOVA P<0.001). VMT≥2 predicted elevated PAWP with an accuracy of 86% and showed an incremental predictive value over clinical variables and guideline-recommended diastolic function grading. These observations were confirmed in the prospective validation cohort. Importantly, VMT≥2 discriminated elevated PAWP with accuracy of 82% in 33 patients with monophasic LV inflow in the derivation cohort. Kaplan-Meier analysis demonstrated that patients with VMT≥2 were at a higher risk of cardiac events than those with VMT≤1 (P<0.001). Conclusions VMT scoring could be a novel additive marker of elevated LVFP and might also be associated with adverse outcomes in HF patients.
Article
Objective: To determine whether relative pulmonary hypertension (PH), defined as the ratio of mean arterial pressure to mean pulmonary artery pressure, is associated with severe acute kidney injury (AKI) post-heart transplant (HT). Design: An Institutional Review Board-approved retrospective observational study. Setting: Tertiary care university hospital. Participants: A total of 184 consecutive adult patients who underwent HT between January 2009 and December 2017 were included, and were followed-up through December 2019. Using the Kidney Disease: Improving Global Outcomes (KDIGO) classification, recipients were divided into two groups: patients who developed stage 3 AKI (severe AKI) and those with minor or without AKI (non-severe AKI) within 7 days post-transplant. Interventions: None. Measurements and Main Results: Of the included patients, 83.2% developed AKI, in whom 40.8%, 19.6%, and 22.8% were stage 1, 2, and 3, respectively. Using the multivariate logistic regression analysis, independent risk factors for stage 3 AKI post-HT included preoperative relative PH (odds ratio [OR]: 1.62, 95% confidence interval [95% CI]: 1.05–2.49, p = 0.028), central venous-to-pulmonary capillary wedge pressure ratio ≥ 0.86 (OR: 3.59, 95% CI: 1.13–11.43, p = 0.030), and postoperative right ventricular dysfunction (OR: 3.63, 95% CI: 1.50–8.75, p = 0.004). Conversely, preoperative estimated glomerular filtration rate (OR: 0.99, 95% CI: 0.97–1.00, p = 0.143) was not related to the development of stage 3 AKI post-HT. Conclusions: Preoperative relative PH, central venous-to-pulmonary capillary wedge pressure ratio, and postoperative right ventricular failure by echocardiographic assessment were associated with severe AKI post-HT.
Chapter
This chapter reviews the most contemporary approach to hemodynamic assessment in heart failure.
Article
Background Relationship between the frequency of occurrence of bendopnea during the daily life of heart failure (HF) outpatients and clinical outcomes has never been evaluated before. Methods Turkish Research Team-Heart Failure (TREAT-HF) is a network between HF centres, which undertakes multicentric observational studies in HF. Herein, the data including stable 573 HF patients with reduced ejection fraction out of seven HF centres were presented. A questionnaire was filled by the patients, with the question ‘Do you experience shortness of breath while tying your shoelace?’, assessing the presence and frequency of bendopnea. Results To the question related to bendopnea, 48% of the patients answered ‘yes, every time’, 31% answered ‘yes, sometimes’, and 21% answered ‘No’. Patients were followed for an average of 24 ± 14 months, and the patients who answered ‘yes, every time’ and ‘yes, sometimes’ to the bendopnea question were found having increased risk for both HF-related hospitalisations (HR:3.2, p < .001- HR:2.8, p = .005) and composite outcome consisting of ‘HF-related hospitalisations and all-cause death in the multi-variate analysis (HR:3.1, p < .001- HR:3.0, p < .001). Kaplan Meier analysis for HF-related hospitalisation, all-cause death, and the composite of these were provided for these three groups, yielding significant and graded divergence curves with the best prognosis in ‘no’ group, with the moderate prognosis in ‘sometimes’ group, and with the worst prognosis in the ‘every time’ group. Conclusion For the first time in the literature, our study shows that the increased frequency of bendopnea occurrence in daily life is associated with poor outcomes in HF outpatients.
Article
Full-text available
The aim of this study was to evaluate the incidence, risk factors, and effect on outcomes of right ventricular failure in a large population of patients implanted with continuous-flow left ventricular assist devices. Patients (n = 484) enrolled in the HeartMate II left ventricular assist device (Thoratec, Pleasanton, Calif) bridge-to-transplantation clinical trial were examined for the occurrence of right ventricular failure. Right ventricular failure was defined as requiring a right ventricular assist device, 14 or more days of inotropic support after implantation, and/or inotropic support starting more than 14 days after implantation. Demographics, along with clinical, laboratory, and hemodynamic data, were compared between patients with and without right ventricular failure, and risk factors were identified. Overall, 30 (6%) patients receiving left ventricular assist devices required a right ventricular assist device, 35 (7%) required extended inotropes, and 33 (7%) required late inotropes. A significantly greater percentage of patients without right ventricular failure survived to transplantation, recovery, or ongoing device support at 180 days compared with patients with right ventricular failure (89% vs 71%, P < .001). Multivariate analysis revealed that a central venous pressure/pulmonary capillary wedge pressure ratio of greater than 0.63 (odds ratio, 2.3; 95% confidence interval, 1.2-4.3; P = .009), need for preoperative ventilator support (odds ratio, 5.5; 95% confidence interval, 2.3-13.2; P < .001), and blood urea nitrogen level of greater than 39 mg/dL (odds ratio, 2.1; 95% confidence interval, 1.1-4.1; P = .02) were independent predictors of right ventricular failure after left ventricular assist device implantation. The incidence of right ventricular failure in patients with a HeartMate II ventricular assist device is comparable or less than that of patients with pulsatile-flow devices. Its occurrence is associated with worse outcomes than seen in patients without right ventricular failure. Patients at risk for right ventricular failure might benefit from preoperative optimization of right heart function or planned biventricular support.
Article
Full-text available
The independent prognostic value of elevated jugular venous pressure or a third heart sound in patients with heart failure is not well established. We performed a retrospective analysis of the Studies of Left Ventricular Dysfunction treatment trial, in which 2569 patients with symptomatic heart failure or a history of it were randomly assigned to receive enalapril or placebo. The mean (+/-SD) follow-up was 32+/-15 months. The presence of elevated jugular venous pressure or a third heart sound was ascertained by physical examination on entry into the trial. The risks of hospitalization for heart failure and progression of heart failure as defined by death from pump failure and the composite end point of death or hospitalization for heart failure were compared in patients with these findings on physical examination and patients without these findings. Data on 2479 patients were complete and analyzed. In multivariate analyses that were adjusted for other markers of the severity of heart failure, elevated jugular venous pressure was associated with an increased risk of hospitalization for heart failure (relative risk, 1.32; 95 percent confidence interval, 1.08 to 1.62; P<0.01), death or hospitalization for heart failure (relative risk, 1.30; 95 percent confidence interval, 1.11 to 1.53; P<0.005), and death from pump failure (relative risk, 1.37; 95 percent confidence interval, 1.07 to 1.75; P<0.05). The presence of a third heart sound was associated with similarly increased risks of these outcomes. In patients with heart failure, elevated jugular venous pressure and a third heart sound are each independently associated with adverse outcomes, including progression of heart failure. Clinical assessment for these findings is currently feasible and clinically meaningful.
Article
Full-text available
Pulmonary artery catheters (PACs) have been used to guide therapy in multiple settings, but recent studies have raised concerns that PACs may lead to increased mortality in hospitalized patients. To determine whether PAC use is safe and improves clinical outcomes in patients hospitalized with severe symptomatic and recurrent heart failure. The Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) was a randomized controlled trial of 433 patients at 26 sites conducted from January 18, 2000, to November 17, 2003. Patients were assigned to receive therapy guided by clinical assessment and a PAC or clinical assessment alone. The target in both groups was resolution of clinical congestion, with additional PAC targets of a pulmonary capillary wedge pressure of 15 mm Hg and a right atrial pressure of 8 mm Hg. Medications were not specified, but inotrope use was explicitly discouraged. The primary end point was days alive out of the hospital during the first 6 months, with secondary end points of exercise, quality of life, biochemical, and echocardiographic changes. Severity of illness was reflected by the following values: average left ventricular ejection fraction, 19%; systolic blood pressure, 106 mm Hg; sodium level, 137 mEq/L; urea nitrogen, 35 mg/dL (12.40 mmol/L); and creatinine, 1.5 mg/dL (132.6 micromol/L). Therapy in both groups led to substantial reduction in symptoms, jugular venous pressure, and edema. Use of the PAC did not significantly affect the primary end point of days alive and out of the hospital during the first 6 months (133 days vs 135 days; hazard ratio [HR], 1.00 [95% confidence interval {CI}, 0.82-1.21]; P = .99), mortality (43 patients [10%] vs 38 patients [9%]; odds ratio [OR], 1.26 [95% CI, 0.78-2.03]; P = .35), or the number of days hospitalized (8.7 vs 8.3; HR, 1.04 [95% CI, 0.86-1.27]; P = .67). In-hospital adverse events were more common among patients in the PAC group (47 [21.9%] vs 25 [11.5%]; P = .04). There were no deaths related to PAC use, and no difference for in-hospital plus 30-day mortality (10 [4.7%] vs 11 [5.0%]; OR, 0.97 [95% CI, 0.38-2.22]; P = .97). Exercise and quality of life end points improved in both groups with a trend toward greater improvement with the PAC, which reached significance for the time trade-off at all time points after randomization. Therapy to reduce volume overload during hospitalization for heart failure led to marked improvement in signs and symptoms of elevated filling pressures with or without the PAC. Addition of the PAC to careful clinical assessment increased anticipated adverse events, but did not affect overall mortality and hospitalization. Future trials should test noninvasive assessments with specific treatment strategies that could be used to better tailor therapy for both survival time and survival quality as valued by patients.
Article
Background— Although right-sided filling pressures often mirror left-sided filling pressures in systolic heart failure, it is not known whether a similar relationship exists in heart failure with preserved ejection fraction. Methods and Results— Eleven subjects with heart failure with preserved ejection fraction underwent right heart catheterization at rest and under loading conditions manipulated by lower body negative pressure and saline infusion. Right atrial pressure (RAP) was classified as elevated when ≥10 mm Hg and pulmonary capillary wedge pressure (PCWP) when ≥22 mm Hg. If both the RAP and the PCWP were elevated or both not elevated, they were classified as concordant; otherwise, they were classified as discordant. Correlation of RAP and PCWP was determined by a repeated measures model. Among 66 paired measurements of RAP and PCWP, 44 (67%) had a low RAP and PCWP and 8 (12%) a high RAP and PCWP, yielding a concordance rate of 79%. In a sensitivity analysis performed by varying the definition of elevated RAP (from 8 to 12 mm Hg) and PCWP (from 15 to 25 mm Hg), the mean±SD concordance of RAP and PCWP was 76±10%. The correlation coefficient of RAP and PCWP for the overall cohort was r =0.86 ( P <0.0001). Conclusions— Right-sided filling pressures often reflect left-sided filling pressures in heart failure with preserved ejection fraction, supporting the role of estimation of jugular venous pressure to assess volume status in this condition.
Article
Context: Estimation of mortality risk in patients hospitalized with acute decompensated heart failure (ADHF) may help clinicians guide care. Objective: To develop a practical user-friendly bedside tool for risk stratification for patients hospitalized with ADHF. Design, Setting, and Patients: The Acute Decompensated Heart Failure National Registry (ADHERE) of patients hospitalized with a primary diagnosis of ADHF in 263 hospitals in the United States was queried with analysis of patient data to develop a risk stratification model. The first 33 046 hospitalizations (derivation cohort; October 2001-February 2003) were analyzed to develop the model and then the validity of the model was prospectively tested using data from 32 229 subsequent hospitalizations (validation cohort; March-July 2003). Patients had a mean age of 72.5 years and 52% were female. Main Outcome Measure: Variables predicting mortality in ADHF. Results: When the derivation and validation cohorts are combined, 37 772 (58%) of 65 275 patient-records had coronary artery disease. Of a combined cohort consisting of 52 164 patient-records, 23 910 (46%) had preserved left ventricular systolic function. In-hospital mortality was similar in the derivation (4.2%) and validation (4.0%) cohorts. Recursive partitioning of the derivation cohort for 39 variables indicated that the best single predictor for mortality was high admission levels of blood urea nitrogen (≥43 mg/dL [15.35 mmol/L]) followed by low admission systolic blood pressure (<115 mm Hg) and then by high levels of serum creatinine (≥2.75 mg/dL [243.1 μmol/L]). A simple risk tree identified patient groups with mortality ranging from 2.1% to 21.9%. The odds ratio for mortality between patients identified as high and low risk was 12.9 (95% confidence interval, 10.4-15.9) and similar results were seen when this risk stratification was applied prospectively to the validation cohort. Conclusions: These results suggest that ADHF patients at low, intermediate, and high risk for in-hospital mortality can be easily identified using vital sign and laboratory data obtained on hospital admission. The ADHERE risk tree provides clinicians with a validated, practical bedside tool for mortality risk stratification.
Article
Estimation of mortality risk in patients hospitalized with acute decompensated heart failure (ADHF) may help clinicians guide care. To develop a practical user-friendly bedside tool for risk stratification for patients hospitalized with ADHF. The Acute Decompensated Heart Failure National Registry (ADHERE) of patients hospitalized with a primary diagnosis of ADHF in 263 hospitals in the United States was queried with analysis of patient data to develop a risk stratification model. The first 33,046 hospitalizations (derivation cohort; October 2001-February 2003) were analyzed to develop the model and then the validity of the model was prospectively tested using data from 32,229 subsequent hospitalizations (validation cohort; March-July 2003). Patients had a mean age of 72.5 years and 52% were female. Variables predicting mortality in ADHF. When the derivation and validation cohorts are combined, 37,772 (58%) of 65,275 patient-records had coronary artery disease. Of a combined cohort consisting of 52,164 patient-records, 23,910 (46%) had preserved left ventricular systolic function. In-hospital mortality was similar in the derivation (4.2%) and validation (4.0%) cohorts. Recursive partitioning of the derivation cohort for 39 variables indicated that the best single predictor for mortality was high admission levels of blood urea nitrogen (> or =43 mg/dL [15.35 mmol/L]) followed by low admission systolic blood pressure (<115 mm Hg) and then by high levels of serum creatinine (> or =2.75 mg/dL [243.1 micromol/L]). A simple risk tree identified patient groups with mortality ranging from 2.1% to 21.9%. The odds ratio for mortality between patients identified as high and low risk was 12.9 (95% confidence interval, 10.4-15.9) and similar results were seen when this risk stratification was applied prospectively to the validation cohort. These results suggest that ADHF patients at low, intermediate, and high risk for in-hospital mortality can be easily identified using vital sign and laboratory data obtained on hospital admission. The ADHERE risk tree provides clinicians with a validated, practical bedside tool for mortality risk stratification.
Article
Right ventricular failure from increased pulmonary vascular loading is a major cause of morbidity and mortality, yet its modulation by disease remains poorly understood. We tested the hypotheses that, unlike the systemic circulation, pulmonary vascular resistance (R(PA)) and compliance (C(PA)) are consistently and inversely related regardless of age, pulmonary hypertension, or interstitial fibrosis and that this relation may be changed by elevated pulmonary capillary wedge pressure, augmenting right ventricular pulsatile load. Several large clinical databases with right heart/pulmonary catheterization data were analyzed to determine the R(PA)-C(PA) relationship with pulmonary hypertension, pulmonary fibrosis, patient age, and varying pulmonary capillary wedge pressure. Patients with suspected or documented pulmonary hypertension (n=1009) and normal pulmonary capillary wedge pressure displayed a consistent R(PA)-C(PA) hyperbolic (inverse) dependence, C(PA)=0.564/(0.047+R(PA)), with a near-constant resistance-compliance product (0.48±0.17 seconds). In the same patients, the systemic resistance-compliance product was highly variable. Severe pulmonary fibrosis (n=89) did not change the R(PA)-C(PA) relation. Increasing patient age led to a very small but statistically significant change in the relation. However, elevation of the pulmonary capillary wedge pressure (n=8142) had a larger impact, significantly lowering C(PA) for any R(PA) and negatively correlating with the resistance-compliance product (P<0.0001). Pulmonary hypertension and pulmonary fibrosis do not significantly change the hyperbolic dependence between R(PA) and C(PA), and patient age has only minimal effects. This fixed relationship helps explain the difficulty of reducing total right ventricular afterload by therapies that have a modest impact on mean R(PA). Higher pulmonary capillary wedge pressure appears to enhance net right ventricular afterload by elevating pulsatile, relative to resistive, load and may contribute to right ventricular dysfunction.
Article
Jugular venous pressure (JVP) is assessed to estimate volume status in patients with heart failure because right atrial pressure (RAP) reflects pulmonary capillary wedge pressure (PCWP). In a large cohort of heart failure patients spanning 14 years, we sought to further characterize the relationship between RAP and PCWP, including identifying temporal trends, to optimize estimates of PCWP by JVP. We also sought to determine whether the RAP to PCWP relationship impacts post-transplant mortality. Hemodynamic data were obtained from 4,079 patients before cardiac transplantation. Elevated RAP was defined as ≥10 mm Hg and elevated PCWP ≥22 mm Hg. Hemodynamics were "concordant" when both RAP and PCWP were elevated or when both were not elevated. The frequency of concordant hemodynamics was assessed over 3 eras (1993 to 1997, 1998 to 2002, 2003 to 2007). Baseline characteristics were compared among quartiles of the ratio (RAP+1)/PCWP. The association of (RAP+1)/PCWP with 2-year mortality after cardiac transplantation was assessed using multivariate models. The frequency of concordant hemodynamics over time was stable (74%, 72%, 73%; p = 0.4). Increasing (RAP+1)/PCWP was associated with the following variables: female gender; cardiomyopathy etiology besides ischemic or non-ischemic; prior sternotomies; and lower creatinine clearance (p < 0.01 for all). Elevated (RAP+1)/PCWP was associated with post-transplant mortality (relative risk 1.2, 95% confidence interval 1.02 to 1.37, p = 0.02). [corrected] RAP and PCWP remain concordant in most heart failure patients, supporting the ongoing use of JVP to estimate PCWP. Easily identifiable patient characteristics were associated with an increased RAP/PCWP ratio, and their presence should alert clinicians that PCWP may be overestimated by JVP assessment. A higher RAP/PCWP ratio was an adverse risk factor for post-cardiac transplant survival.
Article
The prevalence of heart failure with preserved ejection fraction is increasing. The prognosis worsens with pulmonary hypertension and right ventricular (RV) failure development. We targeted pulmonary hypertension and RV burden with the phosphodiesterase-5 inhibitor sildenafil. Forty-four patients with heart failure with preserved ejection fraction (heart failure signs and symptoms, diastolic dysfunction, ejection fraction ≥50%, and pulmonary artery systolic pressure >40 mm Hg) were randomly assigned to placebo or sildenafil (50 mg thrice per day). At 6 months, there was no improvement with placebo, but sildenafil mediated significant improvements in mean pulmonary artery pressure (-42.0±13.0%) and RV function, as suggested by leftward shift of the RV Frank-Starling relationship, increased tricuspid annular systolic excursion (+69.0±19.0%) and ejection rate (+17.0±8.3%), and reduced right atrial pressure (-54.0±7.2%). These effects may have resulted from changes within the lung (reduced lung water content and improved alveolar-capillary gas conductance, +15.8±4.5%), the pulmonary vasculature (arteriolar resistance, -71.0±8.2%), and left-sided cardiac function (wedge pulmonary pressure, -15.7±3.1%; cardiac index, +6.0±0.9%; deceleration time, -13.0±1.9%; isovolumic relaxation time, -14.0±1.7%; septal mitral annulus velocity, -76.4±9.2%). Results were similar at 12 months. The multifaceted response to phosphodiesterase-5 inhibition in heart failure with preserved ejection fraction includes improvement in pulmonary pressure and vasomotility, RV function and dimension, left ventricular relaxation and distensibility (structural changes and/or ventricular interdependence), and lung interstitial water metabolism (wedge pulmonary pressure decrease improving hydrostatic balance and right atrial pressure reduction facilitating lung lymphatic drainage). These results enhance our understanding of heart failure with preserved ejection fraction and offer new directions for therapy. URL: http://www.clinicaltrials.gov. UNIQUE IDENTIFIER: NCT01156636.
Article
In patients with advanced heart failure (HF), elevated jugular venous pressure (JVP) is the most reliable sign of elevated left-sided filling pressures. However, discordance between right- and left-sided filling pressures (R-L mismatch) could lead to inadequate or excessive therapy guided by JVP. We determined the prevalence of R-L mismatch in the current era and investigated whether mismatch might be identified from clinical information. Right-sided heart catheterization was performed in 537 consecutive patients hospitalized with advanced HF during complete transplantation evaluation. Patients with high filling pressures were categorized as matched (right atrial pressure (RAP) ≥10 mm Hg and pulmonary wedge pressure (PCWP) ≥22 mm Hg), high-R mismatch (RAP ≥10 but PCWP <22 mm Hg) or high-L mismatch (PCWP ≥22 but RAP <10 mm Hg). Among all of the patients, 195 (36%) were matched low and 194 (36%) were matched high, and 148 (28%) had R-L mismatch. Among patients with high filling pressures, 194 (57%) were matched high and 82 (24%) had high-L and 66 (19%) high-R mismatch. Mismatches were not associated with differences in demographic or clinical data, including pulmonary and hepatic function, or severity of valvular regurgitation and right ventricular function by echo. However, among all patients with RAP ≥10 mm Hg, pulmonary artery systolic pressure (PASP) was higher in those patients with matched high left- and right-sided pressures (59 ± 12 mm Hg) versus high-R mismatch (41 ± 13 mm Hg; P < .0001). Similarly among all patients with low RAP, PASP was lower in patients with matched low right- and left-side pressures (33 ± 11 mm Hg) versus high-L mismatch (53 ± 13 mm Hg; P < .0001). R-L mismatch was present in >1 in 4 total patients, and >1 in 3 with elevated filling pressures. Regardless of clinical history, when empiric therapy to optimize volume status to JVP is not effective, additional measurement should be considered to establish the R-L relationship.
Article
Pulmonary hypertension (PH) with left-sided heart disease is defined, according to the latest Venice classification, as a Group 2 PH, which includes left-sided ventricular or atrial disease, and left-sided valvular diseases. These conditions are all associated with increased left ventricular filling pressure. Although PH with left-sided heart disease is a common entity, and long-term follow-up trials have provided firm recognition that development of left-sided PH carries a poor outcome, available data on incidence, pathophysiology, and therapy are sparse. Mitral stenosis was reported as the most frequent cause of PH several decades ago, but PH with left-sided heart disease is now usually caused by systemic hypertension and ischemic heart disease. In patients with these conditions, PH develops as a consequence of impaired left ventricular relaxation and distensibility. Chronic sustained elevation of cardiogenic blood pressure in pulmonary capillaries leads to a cascade of untoward retrograde anatomical and functional effects that represent specific targets for therapeutic intervention. The pathophysiological and clinical importance of the hemodynamic consequences of left-sided heart disease, starting with lung capillary injury and leading to right ventricular overload and failure, are discussed in this Review, focusing on PH as an evolving contributor to heart failure that may be amenable to novel interventions.
Article
Although right-sided filling pressures often mirror left-sided filling pressures in systolic heart failure, it is not known whether a similar relationship exists in heart failure with preserved ejection fraction. Eleven subjects with heart failure with preserved ejection fraction underwent right heart catheterization at rest and under loading conditions manipulated by lower body negative pressure and saline infusion. Right atrial pressure (RAP) was classified as elevated when >or=10 mm Hg and pulmonary capillary wedge pressure (PCWP) when >or=22 mm Hg. If both the RAP and the PCWP were elevated or both not elevated, they were classified as concordant; otherwise, they were classified as discordant. Correlation of RAP and PCWP was determined by a repeated measures model. Among 66 paired measurements of RAP and PCWP, 44 (67%) had a low RAP and PCWP and 8 (12%) a high RAP and PCWP, yielding a concordance rate of 79%. In a sensitivity analysis performed by varying the definition of elevated RAP (from 8 to 12 mm Hg) and PCWP (from 15 to 25 mm Hg), the mean+/-SD concordance of RAP and PCWP was 76+/-10%. The correlation coefficient of RAP and PCWP for the overall cohort was r=0.86 (P<0.0001). Right-sided filling pressures often reflect left-sided filling pressures in heart failure with preserved ejection fraction, supporting the role of estimation of jugular venous pressure to assess volume status in this condition.
Article
Identifying high-risk heart failure (HF) patients at hospital discharge may allow more effective triage to management strategies. Heart failure severity at presentation predicts outcomes, but the prognostic importance of clinical status changes due to interventions is less well described. Predictive models using variables obtained during hospitalization were created using data from the ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) trial and internally validated by the bootstrapping method. Model coefficients were converted to an additive risk score. Additionally, data from FIRST (Flolan International Randomized Survival Trial) was used to externally validate this model. Patients discharged with complete data (n = 423) had 6-month mortality and death and rehospitalization rates of 18.7% and 64%, respectively. Discharge risk factors for mortality included BNP, per doubling (hazard ratio [HR]: 1.42, 95% confidence interval [CI]: 1.15 to 1.75), cardiopulmonary resuscitation or mechanical ventilation during hospitalization (HR: 2.54, 95% CI: 1.12 to 5.78), blood urea nitrogen, per 20-U increase (HR: 1.22, 95% CI: 0.96 to 1.55), serum sodium, per unit increase (HR: 0.93, 95% CI: 0.87 to 0.99), age >70 years (HR: 1.05, 95% CI: 0.51 to 2.17), daily loop diuretic, furosemide equivalents >240 mg (HR: 1.49, 95% CI: 0.68 to 3.26), lack of beta-blocker (HR: 1.28, 95% CI: 0.68 to 2.41), and 6-min walk, per 100-foot increase (HR: 0.955, 95% CI: 0.99 to 1.00; c-index 0.76). A simplified discharge score discriminated mortality risk from 5% (score = 0) to 94% (score = 8). Bootstrap validation demonstrated good internal validation of the model (c-index 0.78, 95% CI: 0.68 to 0.83). The ESCAPE study discharge risk model and score refine risk assessment after in-hospital therapy for advanced decompensated systolic HF, allowing clinicians to focus surveillance and triage for early life-saving interventions in this high-risk population. (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness [ESCAPE]; NCT00000619).
Article
Dynamic mitral regurgitation (MR) contributes to decompensation in chronic dilated heart failure. Reduction of MR was the primary physiological end point in the ESCAPE trial, which compared acute therapy guided by jugular venous pressure, edema, and weight (CLIN) with therapy guided additionally by pulmonary artery catheters (PAC) toward pulmonary wedge pressure <or=15 and right atrial pressure <or=8 mm Hg. Patients were randomized to PAC or CLIN during hospitalization with chronic heart failure and mean left ventricular ejection fraction 20%, and at least 1 symptom and 1 sign of congestion. MR and mitral flow patterns, measured blinded to therapy and timepoint, were available at baseline and discharge in 133 patients, and at 3 months in 104 patients. Changes in MR and related transmitral flow patterns were compared between PAC and CLIN patients. Jugular venous pressure, edema, and weights decreased similarly during therapy in the hospital for both groups. In PAC but not in CLIN patients, MR jet area, MR/left atrial area ratio, and E velocity were each significantly reduced and deceleration time increased by discharge. By 3 months, patients had clinical evidence of increased jugular venous pressure, edema, and weight since discharge, reaching significance in the PAC arm, and the change in MR was no longer different between the 2 groups, although the change in E velocity remained greater in PAC patients. During hospitalization, therapy guided by PAC to reduce left-sided pressures improved MR and related filling patterns more than therapy guided clinically by evidence of systemic venous congestion. This early reduction did not translate into improved outcomes out of the hospital, where volume status reverted toward baseline.
Article
We determined whether estimated hemodynamics from history and physical examination (H&P) reflect invasive measurements and predict outcomes in advanced heart failure (HF). The role of the H&P in medical decision making has declined in favor of diagnostic tests, perhaps due to lack of evidence for utility. We compared H&P estimates of filling pressures and cardiac index with invasive measurements in 194 patients in the ESCAPE trial. H&P estimates were compared with 6-month outcomes in 388 patients enrolled in ESCAPE. Measured right atrial pressure (RAP) was <8 mm Hg in 82% of patients with RAP estimated from jugular veins as <8 mm Hg, and was >12 mm Hg in 70% of patients when estimated as >12 mm Hg. From the H&P, only estimated RAP > or =12 mm Hg (odds ratio [OR] 4.6; P<0.001) and orthopnea > or =2 pillows (OR 3.6; P<0.05) were associated with pulmonary capillary wedge pressure (PCWP) > or =30 mm Hg. Estimated cardiac index did not reliably reflect measured cardiac index (P=0.09), but "cold" versus "warm" profile was associated with lower median measured cardiac index (1.75 vs. 2.0 L/min/m(2); P=0.004). In Cox regression analysis, discharge "cold" or "wet" profile conveyed a 50% increased risk of death or rehospitalization. In advanced HF, the presence of orthopnea and elevated jugular venous pressure are useful to detect elevated PCWP, and a global assessment of inadequate perfusion ("cold" profile) is useful to detect reduced cardiac index. Hemodynamic profiles estimated from the discharge H&P identify patients at increased risk of early events.
Article
To determine whether venous congestion, rather than impairment of cardiac output, is primarily associated with the development of worsening renal function (WRF) in patients with advanced decompensated heart failure (ADHF). Reduced cardiac output is traditionally believed to be the main determinant of WRF in patients with ADHF. A total of 145 consecutive patients admitted with ADHF treated with intensive medical therapy guided by pulmonary artery catheter were studied. We defined WRF as an increase of serum creatinine >/=0.3 mg/dl during hospitalization. In the study cohort (age 57 +/- 14 years, cardiac index 1.9 +/- 0.6 l/min/m(2), left ventricular ejection fraction 20 +/- 8%, serum creatinine 1.7 +/- 0.9 mg/dl), 58 patients (40%) developed WRF. Patients who developed WRF had a greater central venous pressure (CVP) on admission (18 +/- 7 mm Hg vs. 12 +/- 6 mm Hg, p < 0.001) and after intensive medical therapy (11 +/- 8 mm Hg vs. 8 +/- 5 mm Hg, p = 0.04). The development of WRF occurred less frequently in patients who achieved a CVP <8 mm Hg (p = 0.01). Furthermore, the ability of CVP to stratify risk for development of WRF was apparent across the spectrum of systemic blood pressure, pulmonary capillary wedge pressure, cardiac index, and estimated glomerular filtration rates. Venous congestion is the most important hemodynamic factor driving WRF in decompensated patients with advanced heart failure.
Article
We sought to investigate the relationship between increased central venous pressure (CVP), renal function, and mortality in a broad spectrum of cardiovascular patients. The pathophysiology of impaired renal function in cardiovascular disease is multifactorial. The relative importance of increased CVP has not been addressed previously. A total of 2,557 patients who underwent right heart catheterization in the University Medical Center Groningen, the Netherlands, between January 1, 1989, and December 31, 2006, were identified, and their data were extracted from electronic databases. Estimated glomerular filtration rate (eGFR) was assessed with the simplified modification of diet in renal disease formula. Mean age was 59 +/- 15 years, and 57% were men. Mean eGFR was 65 +/- 24 ml/min/1.73 m(2), with a cardiac index of 2.9 +/- 0.8 l/min/m(2) and CVP of 5.9 +/- 4.3 mm Hg. We found that CVP was associated with cardiac index (r = -0.259, p < 0.0001) and eGFR (r = -0.147, p < 0.0001). Also, cardiac index was associated with eGFR (r = 0.123, p < 0.0001). In multivariate analysis CVP remained associated with eGFR (r = -0.108, p < 0.0001). In a median follow-up time of 10.7 years, 741 (29%) patients died. We found that CVP was an independent predictor of reduced survival (hazard ratio: 1.03 per mm Hg increase, 95% confidence interval: 1.01 to 1.05, p = 0.0032). Increased CVP is associated with impaired renal function and independently related to all-cause mortality in a broad spectrum of patients with cardiovascular disease.
Article
To determine the effect of the intact pericardium on ventricular end-diastolic pressures (EDP) during acute volume loading, we measured left ventricular (LV) and right ventricular (RV) micromanometer pressure and LV volume using a conductance catheter in eight open-chest, anesthetized dogs. A range of LV pressure and volume was obtained by intravascular volume expansion with the pericardium intact and then over a similar range after removal of the pericardium. Pericardial pressure (Pper) was calculated using static equilibrium analysis as the difference between LVEDP with the pericardium present and absent at a constant LV volume. At the beginning of the fluid infusion (LVEDP 7.3 +/- 1.7 mmHg and RVEDP 4.4 +/- 2.6 mmHg, mean +/- SD), Pper was not different from zero (-1.0 +/- 2.3 mmHg, P not significant). The onset of pericardial restraint (Pper greater than or equal to 0 mmHg) occurred when LVEDP was 9.1 +/- 2.9 mmHg and RVEDP was 4.1 +/- 2.9 mmHg. At low cardiac volumes before fluid infusion, RV transmural pressure was positive and significantly greater than the near zero Pper. After the onset of pericardial restraint, however, RVEDP and Pper increased similarly and were related according to Pper = 1.1 (+/- 0.34) RVEDP - 4.2 (+/- 2.6) mmHg, standard deviation 0.6 +/- 0.8 mmHg, r = 0.98 +/- 0.10. These data indicate that the intact pericardium behaves in two functionally distinct ways. At low cardiac volumes, Pper is zero and the pericardium does not affect LV filling. RV transmural pressure is positive and greater than Pper.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
This study was undertaken to determine which exercise and radionuclide ventriculographic variables predict prognosis in advanced heart failure. Although cardiopulmonary exercise testing is frequently used to predict prognosis in patients with advanced heart failure, little is known about the prognostic significance of ventriculographic variables. The results of maximal symptom-limited cardiopulmonary exercise testing and first-pass radionuclide ventriculography in patients with advanced heart failure referred for evaluation for cardiac transplantation were analyzed. Sixty-seven patients with advanced heart failure (mean [+/- SD]; age 51 +/- 10 years, New York Heart Association functional classes III (58%) and IV (18%); mean left ventricular ejection fraction 0.22 +/- 0.07) underwent simultaneous upright bicycle ergometric cardiopulmonary exercise testing and first-pass rest/exercise radionuclide ventriculography. Mean peak oxygen consumption (VO2) was 11.8 +/- 4.2 ml/kg per min, and mean peak age- and gender-adjusted percent predicted oxygen consumption (%VO2) was 38 +/- 11.9%. Univariate predictors of overall survival included right ventricular ejection fraction > or = 0.35 at rest and > or = 0.35 at exercise and %VO2 > or = 45% (all p < 0.05). In a multivariate proportional hazards survival model, right ventricular ejection fraction > or = 0.35 at exercise (p < 0.01) and %VO2 > or = 45% (p = 0.01) were selected as independent predictors of overall survival. Univariate predictors of event-free survival included right ventricular ejection fraction > or = 0.35 at rest (p = 0.01) and > or = 0.35 at exercise (p < 0.01), functional class II (p < 0.05) and %VO2 > or = 45% (p = 0.05). Right ventricular ejection fraction > or = 0.35 at exercise (p = 0.01) was the only independent predictor of event-free survival in a multivariate proportional hazards model. Cardiac index at rest, VO2, left ventricular ejection fraction at rest, and exercise-related increase or decrease > 0.05 in left or right ventricular ejection fraction were not predictive of overall or event-free survival in any univariate or multivariate analysis. 1) Right ventricular ejection fraction > or = 0.35 at rest and exercise is a more potent predictor of survival in advanced heart failure than VO2 or %VO2; 2) %VO2 rather than VO2 predicts survival in advanced heart failure; 3) neither %VO2 nor VO2 predicts survival to the combined end point of death or admission for inotropic or mechanical support in patients with advanced heart failure.
Article
Background: Diastolic ventricular interaction describes a situation in which the volume of one ventricle is directly influenced by the volume of the other ventricle. Such interaction is normally negligible, but it is accentuated in circumstances associated with pulmonary hypertension and volume overload. When this interaction occurs, acute volume unloading results in a reduction in right ventricular end-diastolic volume, as expected, but left ventricular end-diastolic volume paradoxically increases. Since chronic heart failure is a volume-overloaded state associated with pulmonary hypertension, we hypothesised that this interaction may be clinically important in patients with heart failure. Methods: A radionuclide technique incorporating cardiac scintigraphy was used to measure the effect of acute volume unloading, achieved by 30 mm Hg lower-body suction, on right and left ventricular end-diastolic volumes in 21 patients with chronic heart failure and 12 healthy individuals (controls). Findings: In nine heart-failure patients, there was a paradoxical increase in left ventricular end-diastolic volume in association with an expected decrease in right ventricular end-diastolic volume during lower-body suction. This response was not seen in the control group. The mean change in left ventricular end-diastolic volume differed significantly between the heart-failure patients and controls (6 [SD 19] vs -19 [12] mL, p = 0.0003). However, the change in right ventricular end-diastolic volume was similar in the two groups (-18 [11] vs -20 [8]%. p = 0.70). Patients who increased left ventricular end-diastolic volume during lower-body suction had higher resting pulmonary arterial and pulmonary capillary wedge pressures than the remaining heart-failure patients. Interpretation: The response of nine patients in our study suggests diastolic ventricular interaction, which we believe could be common in patients with chronic heart failure. This finding is relevant to their management, since it emphasises the importance of venodilator therapy. The relation between stroke volume and left ventricular end-diastolic volume, by the Frank-Starting law of the heart, may explain why some patients with chronic heart failure paradoxically increase stroke volume when pulmonary capillary wedge pressure is lowered with vasodilators.
Article
Elevated left ventricular filling pressures present a major target of therapy for symptomatic heart failure but are difficult to assess directly. Because the relationship of left- and right-sided pressures remains ill defined in chronic heart failure, this study compared 3 right-sided measurements (right atrial [RA] pressure, pulmonary artery systolic [PAS] pressure, and severity of tricuspid regurgitation [TR]) to the pulmonary capillary wedge (PCW) pressure. Hemodynamic measurements and echocardiography were available from 1000 patients undergoing transplant evaluation. Right atrial and PAS pressure, and TR severity were compared to PCW pressure. For 754 patients undergoing repeat measurements, changes in RA and PAS pressures were compared to PCW changes. Right atrial pressure correlated with PCW pressure (r = 0.64), regardless of etiology or TR severity. Right atrial pressure changes correlated with PCW changes (r = 0.62). Discordance was defined as either RA > or = 10 mm Hg despite PCW < 22 mm Hg (6%) or RA < 10 mm Hg despite PCW > or = 22 mm Hg (15%). For detection of PCW > or = 22 mm Hg, positive predictive values were 88% for RA > or = 10 mm Hg, 95% for PAS > or = 60 mm Hg, and 79% for > or = moderate TR. Pulmonary artery systolic pressure correlated very closely with PCW (r = 0.79), and could be estimated as 2 x PCW. Reduction in PAS pressure during therapy was strongly determined by PCW pressure reduction (r = 0.67). Accurate estimation of RA pressure can potentially guide therapy of left ventricular filling pressures in approximately 80% of chronic heart failure patients without obvious non-cardiac disease. In this population, elevated PAS pressures are largely determined by elevated left-sided filling pressures.
Article
We sought a better understanding of the coupling between right ventricular ejection fraction (RVEF) and pulmonary artery pressure (PAP), as it might improve the accuracy of the prognostic stratification of patients with heart failure. Despite the long-standing view that systolic function of the right ventricle (RV) is almost exclusively dependent on the afterload that this cardiac chamber must confront, recent studies claim that RV function is an independent prognostic factor in patients with chronic heart failure. Right heart catheterization was performed in 377 consecutive patients with heart failure. During a median follow-up period of 17 +/- 9 months, 105 patients died and 35 underwent urgent heart transplantation. Pulmonary artery pressure and thermodilution-derived RVEF were inversely related (r = 0.66, p < 0.001). However, on Cox multivariate survival analysis, no interaction between such variables was found, and both turned out to be independent prognostic predictors (p < 0.001). It was found that RVEF was preserved in some patients with pulmonary hypertension, and that the prognosis of these patients was similar to that of the patients with normal PAP. In contrast, when PAP was normal, reduced RV function did not carry an additional risk. These observations emphasize the necessity of combining the right heart hemodynamic variables with a functional evaluation of the RV when trying to define the individual risk of patients with heart failure.
Article
Glomerular filtration rate (GFR) has major prognostic implications in heart failure. Our objective was to validate the MDRD prediction equations for GFR in patients with advanced heart failure, and to compare their predictive performance to that of the Cockcroft-Gault (CG) equation. We analysed GFR in 45 patients referred for heart transplantation evaluation. 51Cr-EDTA-measured GFR was compared to GFR estimates obtained by MDRD1 and MDRD2 equations, CG equation using actual body weight, and ideal body weight. Regression analyses and Pearson correlations were performed, and Bland and Altman plots were drawn. ROC curves were obtained to illustrate each equation's ability to predict a GFR less than 60 ml/min/1.73 m2 (moderate renal impairment). Patients had a mean age of 52 years, and 69% were in NYHA class III. The mean EDTA-measured GFR was 46.9+/-17.2 ml/min/1.73 m2. The MDRD1 equation provided the best predictive model (narrowest limits of agreement; r = 0.766, p < 0.001), and the highest performance in predicting a GFR less than 60 ml/min/1.73 m2 (area under curve: 0.901). MDRD equations, especially MDRD1, adequately predict GFR in advanced heart failure, with higher accuracy than the CG equation. MDRD1 also has higher performance in predicting a GFR less than 60 ml/min/1.73 m2.
Article
We examined the ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) database to understand the impact and pathophysiology of renal dysfunction in patients hospitalized with advanced decompensated heart failure (HF). Baseline renal insufficiency (RI) (estimated glomerular filtration rate [eGFR] <60 ml/min) and worsening renal function (WRF) (upward arrow serum creatinine [SCr] >or=0.3 mg/dl) during treatment of decompensated HF are associated with adverse outcomes. We used a Cox proportional hazards model to evaluate the impact of renal function on 6-month outcomes. Renal parameters were correlated with hemodynamic measurements. The impact of a strategy using pulmonary artery catheter (PAC) guidance on WRF and outcomes in patients with baseline RI was compared with treatment based on clinical assessment alone. Baseline and discharge RI, but not WRF, were associated with an increased risk of death and death or rehospitalization. Among the hemodynamic parameters measured in patients randomized to the PAC arm (n = 194), only right atrial pressure correlated weakly with baseline SCr (r = 0.165, p = 0.03). There was no correlation between baseline hemodynamics or change in hemodynamics and WRF. A PAC-guided strategy was associated with less average increase in creatinine but did not decrease the incidence of defined WRF during hospitalization or affect renal function after discharge relative to clinical assessment alone. Among patients with advanced decompensated HF, baseline RI impacts outcomes more than WRF. Poor forward flow alone does not appear to account for the development of RI or WRF in these patients. The addition of hemodynamic monitoring to clinical assessment does not prevent WRF or improve renal function after discharge.
The Modification of Diet in Renal Disease (MDRD) equations provide valid estimations of glomerular filtration rates in patients with advanced heart failure
  • O Meara
  • E Chong
  • Ks Gardner
  • Rs Jardine
  • Ag Neilly
  • Jb Mcdonagh
O'Meara E, Chong KS, Gardner RS, Jardine AG, Neilly JB, McDonagh TA. The Modification of Diet in Renal Disease (MDRD) equations provide valid estimations of glomerular filtration rates in patients with advanced heart failure. Eur J Heart Fail. 2006;8:63–67.
Importance of venous congestion for worsening of renal function in advanced decompensated heart failure
  • R J Tedford
  • P M Hassoun
  • S C Mathai
  • R E Girgis
  • S D Russell
  • D R Thiemann
  • O H Cingolani
  • J O Mudd
  • B A Borlaug
  • M M Redfield
  • D J Lederer
  • Kass Da
Tedford RJ, Hassoun PM, Mathai SC, Girgis RE, Russell SD, Thiemann DR, Cingolani OH, Mudd JO, Borlaug BA, Redfield MM, Lederer DJ, Kass DA. Importance of venous congestion for worsening of renal function in advanced decompensated heart failure. J Am Coll Cardiol. 2009;53:589-96.
Triage after hospitalization with advanced heart failure: the ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) risk model and discharge score
  • O Connor
  • Cm Hasselblad
  • V Mehta
  • Rh Tasissa
  • G Califf
  • Rm Fiuzat
  • M Rogers
  • Jg Leier
  • Cv Stevenson
O'Connor CM, Hasselblad V, Mehta RH, Tasissa G, Califf RM, Fiuzat M, Rogers JG, Leier CV, Stevenson LW. Triage after hospitalization with advanced heart failure: the ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) risk model and discharge score. J Am Coll Cardiol. 2010;55:872-878.
Preserved right ventricular ejection fraction predicts exercise capacity and survival in advanced heart failure
  • Di Salvo
  • T G Mathier
  • M Semigran
  • M J Dec
Di Salvo TG, Mathier M, Semigran MJ, Dec GW. Preserved right ventricular ejection fraction predicts exercise capacity and survival in advanced heart failure. J Am Coll Cardiol. 1995;25:1143-1153.