[Show abstract][Hide abstract] ABSTRACT: Although much is known about the risk factors for poor outcome in patients hospitalized with acute heart failure and left ventricular dysfunction, much less is known about the syndrome of acute heart failure primarily affecting the right ventricle (acute right heart failure).
By using Stanford Hospital's pulmonary hypertension database, we identified consecutive acute right heart failure hospitalizations in patients with PAH. We used longitudinal regression analysis with the generalized estimating equations method to identify factors associated with an increased likelihood of 90-day mortality or urgent transplantation. From June 1999 to September 2009, 119 patients with PAH were hospitalized for acute right heart failure (207 episodes). Death or urgent transplantation occurred in 34 patients by 90 days of admission. Multivariable analysis identified a higher respiratory rate on admission (>20 breaths per minute; OR, 3.4; 95% CI, 1.5-7.8), renal dysfunction on admission (glomerular filtration rate <45 mL/min per 1.73 m2; OR, 2.7; 95% CI, 1.2-6.3), hyponatremia (serum sodium ≤136 mEq/L; OR, 3.6; 95% CI, 1.7-7.9), and tricuspid regurgitation severity (OR, 2.5 per grade; 95% CI, 1.2-5.5) as independent factors associated with an increased likelihood of death or urgent transplantation.
These results highlight the high mortality after hospitalizations for acute right heart failure in patients with PAH. Factors identifiable within hours of hospitalization may help predict the likelihood of death or the need for urgent transplantation in patients with PAH.
[Show abstract][Hide abstract] ABSTRACT: Background. Currently there are no reliable predictors of response to cardiac resynchronization therapy (CRT) before implantation. We compared pre-CRT left ventricular (LV) dyssynchrony by tissue Doppler imaging (TDI) and regional volumetric analysis by 3-dimensional transthoracic echocardiography (3DTTE) in predicting response to CRT. Methods. Thirty-eight patients (79% nonischemic cardiomyopathy) with symptomatic heart failure who underwent CRT were enrolled. Clinical and echocardiographic responses were defined as improvement in one NYHA class and reduction in LV end-systolic volume by ≥15% respectively. Functional status was assessed by Minnesota Living with Heart Failure questionnaire and 6-minute walk distance. Results. In 33 patients, after CRT for 7.86 ± 2.27 months, there were 24 (73%) clinical and 19 (58%) echocardiographic responders. Functional parameters, LV dimensions, volumes and synchrony by TDI and 3DTTE improved significantly in responders. There was no difference in the number of responders and nonresponders when cut-off values for dyssynchrony by different measurements validated in other trials were applied. Area under receiver-operating-characteristic curve ranged from 0.4 to 0.6. Conclusion. CRT improves clinical and echocardiographic parameters in patients with systolic heart failure. The dyssynchrony measurements by TDI and 3DTTE are not comparable and are unable to predict response to CRT.
[Show abstract][Hide abstract] ABSTRACT: Cardiac resynchronization therapy improves morbidity and mortality in appropriately selected patients. Whether atrioventricular (AV) and interventricular (VV) pacing interval optimization confers further clinical improvement remains unclear. A variety of techniques are used to estimate optimum AV/VV intervals; however, the precision of their estimates and the ramifications of an imprecise estimate have not been characterized previously.
An objective methodology for quantifying the precision of estimated optimum AV/VV intervals was developed, allowing physiologic effects to be distinguished from measurement variability. Optimization using multiple conventional techniques was conducted in individual sessions with 20 patients. Measures of stroke volume and dyssynchrony were obtained using impedance cardiography and echocardiographic methods, specifically, aortic velocity-time integral, mitral velocity-time integral, A-wave truncation, and septal-posterior wall motion delay. Echocardiographic methods yielded statistically insignificant data in the majority of patients (62%-82%). In contrast, impedance cardiography yielded statistically significant results in 84% and 75% of patients for AV and VV interval optimization, respectively. Individual cases demonstrated that accepting a plausible but statistically insignificant estimated optimum AV or VV interval can result in worse cardiac function than default values.
Consideration of statistical significance is critical for validating clinical optimization data in individual patients and for comparing competing optimization techniques. Accepting an estimated optimum without knowledge of its precision can result in worse cardiac function than default settings and a misinterpretation of observed changes over time. In this study, only impedance cardiography yielded statistically significant AV and VV interval optimization data in the majority of patients.
[Show abstract][Hide abstract] ABSTRACT: Responders to cardiac resynchronization therapy (CRT) have greater left ventricular (LV) dyssynchrony than nonresponders prior to CRT.
We conducted this study to see whether the long term responders have more worsening of LV dyssynchrony and LV function on acute interruption of CRT.
We identified 22 responders and 13 nonresponders who received CRT as per standard criteria for 23.73 +/- 7.9 months (median 24.5 months). We assessed the acute change in LV function, mitral regurgitation (MR) and compared LV dyssynchrony in CRT on and off modes.
On turning off CRT, there was no significant worsening of LV dyssynchrony in both responders and nonresponders. The dyssynchrony measurements by SPWMD, TDI and 3D echocardiography did not correlate significantly. LVESV increased (p = 0.02) and MR (p = 0.01) worsened in CRT-off mode in responders only without significant change in LVEF or LV dimensions. Discussion and
In long-term responders to CRT, there is alteration in the function of remodeled LV with acute interruption of CRT, without significant worsening of LV dyssynchrony. The role of different echocardiographic parameters in the assessment of LV dyssynchrony remains controversial. Even after long-term CRT reversely remodels the LV, the therapy needs to be continued uninterrupted for sustained benefits.
[Show abstract][Hide abstract] ABSTRACT: Chest pain is a common complaint in patients with pulmonary arterial hypertension (PAH). Left main coronary artery (LMCA) compression by an enlarged pulmonary artery trunk (PAT) has been associated with angina, but appropriate diagnostic and treatment approaches remain poorly defined. We present two cases of angina caused by LMCA compression from an enlarged pulmonary artery, one of which also presented with new, severe left ventricular systolic dysfunction attributed to myocardial ischemia. Diagnosis of LMCA stenosis was made via coronary angiography followed by computed tomography-gated coronary angiography (CT-CA), which confirmed pulmonary artery enlargement as the source of extrinsic compression. Restoring LMCA patency with percutaneous intervention and/or aggressive treatment of pulmonary hypertension led to significant improvement in angina, cardiac function and quality of life. Given the negative impact on cardiac function, prompt diagnosis and treatment of extrinsic LMCA compression should be considered a priority.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 06/2009; 28(5):527-30. DOI:10.1016/j.healun.2008.12.008 · 5.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Rapamycin has been shown to reduce anatomical evidence of cardiac allograft vasculopathy, but its effect on coronary artery physiology is unknown.
Twenty-seven patients without angiographic evidence of coronary artery disease underwent measurement of fractional flow reserve (FFR), coronary flow reserve (CFR), and the index of microcirculatory resistance (IMR) within 8 weeks and then 1 year after transplantation using a pressure sensor/thermistor-tipped guidewire. Measurements were compared between consecutive patients who were on rapamycin for at least 3 months during the first year after transplantation (rapamycin group, n = 9) and a comparable group on mycophenolate mofetil (MMF) instead (MMF group, n = 18).
At baseline, there was no significant difference in FFR, CFR, or IMR between the 2 groups. At 1 year, FFR declined significantly in the MMF group (0.87 +/- 0.06 to 0.82 +/- 0.06, P = .009) but did not change in the rapamycin group (0.91 +/- 0.05 to 0.89 +/- 0.04, P = .33). Coronary flow reserve and IMR did not change significantly in the MMF group (3.1 +/- 1.7 to 3.2 +/- 1.0, P = .76; and 27.5 +/- 18.1 to 19.1 +/- 7.6, P = .10, respectively) but improved significantly in the rapamycin group (2.3 +/- 0.8 to 3.8 +/- 1.4, P < .03; and 27.0 +/- 11.5 to 17.6 +/- 7.5, P < .03, respectively). Multivariate regression analysis revealed that rapamycin therapy was an independent predictor of CFR and FFR at 1 year after transplantation.
Early after cardiac transplantation, rapamycin therapy is associated with improved coronary artery physiology involving both the epicardial vessel and the microvasculature.
American heart journal 05/2008; 155(5):889.e1-6. DOI:10.1016/j.ahj.2008.02.004 · 4.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The objective of this study is to evaluate the predictive value of the index of microcirculatory resistance (IMR) in patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI).
Despite adequate epicardial artery reperfusion, a number of patients with STEMI have a poor prognosis because of microvascular damage. Assessing the status of the microvasculature in this setting remains challenging.
In 29 patients after primary PCI for STEMI, IMR was measured with a pressure sensor/thermistor-tipped guidewire. The Thrombolysis In Myocardial Infarction (TIMI) myocardial perfusion grade, TIMI frame count, coronary flow reserve, and ST-segment resolution were also recorded.
The IMR correlated significantly with the peak creatinine kinase (CK) (R = 0.61, p = 0.0005) while the other measures of microvascular dysfunction did not. In patients with an IMR greater than the median value of 32 U, the peak CK was significantly higher compared with those having values <or=32 U (3,128 +/- 1,634 ng/ml vs. 1,201 +/- 911 ng/ml, p = 0.002). The IMR correlated significantly with 3-month echocardiographic wall motion score (WMS) (R = 0.59, p = 0.002) while the other measures of microvascular function did not. The WMS at 3-month follow-up was significantly worse in the group with an IMR >32 U compared with <or=32 U (28 +/- 7 vs. 20 +/- 4, p = 0.001). On multivariate analysis, IMR was the strongest predictor of peak CK and 3-month WMS. The IMR was the only significant predictor of recovery of left ventricular function on the basis of the percent change in WMS (R = 0.50, p < 0.01).
Compared to standard measures, IMR appears to be a better predictor of microvascular damage after STEMI, both acutely and in short term follow-up.
Journal of the American College of Cardiology 03/2008; 51(5):560-5. DOI:10.1016/j.jacc.2007.08.062 · 15.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Our purpose was to evaluate the impact of nesiritide on renal function in patients with acute decompensated heart failure and baseline renal dysfunction.
Although nesiritide is approved for the treatment of acute decompensated heart failure, retrospective analyses have raised concerns that it may cause worsened renal function. To date, no randomized clinical trials have prospectively evaluated this issue.
Consecutive patients with acute decompensated heart failure and baseline renal dysfunction were enrolled in this randomized, double-blind, placebo-controlled clinical trial. Subjects were randomized to receive nesiritide (0.01 microg/kg/min with or without a 2-microg/kg bolus) or placebo (5% dextrose in water) for 48 h in addition to their usual care. Predefined primary end points of the trial were a rise in serum creatinine by > or =20% and change in serum creatinine.
Seventy-five patients were enrolled (39 nesiritide, 36 placebo). The groups had similar baseline age (74.9 vs. 75.5 years, respectively), blood pressure (123/64 vs. 125/64 mm Hg) and serum creatinine (1.82 vs. 1.86 mg/dl). There were no significant differences in the incidence of a 20% creatinine rise (23% vs. 25%) or in the change in serum creatinine (-0.05 vs. +0.05 mg/dl). There were no significant differences in the secondary end points of change in weight (-2.19 vs. -1.58 kg), intravenous furosemide (125 vs. 107 mg), discontinuation of the infusion due to hypotension (13% vs. 6%), or 30-day death/hospital readmission (33% vs. 25%).
In this randomized, double-blind, placebo-controlled clinical trial, nesiritide had no impact on renal function in patients with acute decompensated heart failure. (BNP-CARDS trial; http://www.clinicaltrials.gov/ct/show/NCT00186329?order=1; NCT00186329).
Journal of the American College of Cardiology 11/2007; 50(19):1835-40. DOI:10.1016/j.jacc.2007.03.071 · 15.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The ongoing shortage of donors for cardiac transplantation has led to a trend toward acceptance of donor hearts with some structural abnormalities including left ventricular hypertrophy. To evaluate the outcome in recipients of donor hearts with increased left ventricular wall thickness (LVWT), we retrospectively analyzed data for 157 cardiac donors and respective recipients from January 2001 to December 2004. There were 47 recipients of donor heart with increased LVWT >or=1.2 cm, which constituted the study group and 110 recipients of a donor heart with normal LVWT < 1.2 cm that formed the control group. At 3 +/- 1.5 years, recipient survival was lower (50% vs. 82%, p = 0.0053) and incidence of allograft vasculopathy was higher (50% vs. 22%, p = 0.05) in recipients of donor heart with LVWT > 1.4 cm as compared to LVWT <or= 1.4 cm. By Cox regression, donor LVWT > 1.4 cm (p = 0.003), recipient preoperative ventricular assist device (VAD) support (p = 0.04) and bypass time > 150 min (p = 0.05) were predictors of reduced survival. Our results suggest careful consideration of donor hearts with echocardiographic evidence of increased LVWT in the absence of hypovolemia, because they may be associated with poorer outcomes; such hearts should potentially be reserved only for the most desperately ill recipients.
American Journal of Transplantation 10/2007; 7(10):2388-95. DOI:10.1111/j.1600-6143.2007.01930.x · 6.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cardiac allograft vasculopathy (CAV) is a progressive process involving the epicardial and microvascular coronary systems. The timing of the development of abnormalities in these 2 compartments and the correlation between changes in physiology and anatomy are undefined. The invasive evaluation of coronary artery anatomy and physiology with intravascular ultrasound, fractional flow reserve, coronary flow reserve, and the index of microcirculatory resistance (IMR) was performed in the left anterior descending coronary artery during 151 angiographic evaluations of asymptomatic heart transplant recipients from 0 to >5 years after heart transplantation (HT). There was no angiographic evidence of significant CAV, but during the first year after HT, fractional flow reserve decreased significantly (0.89 +/- 0.06 vs 0.85 +/- 0.07, p = 0.001), and percentage plaque volume derived by intravascular ultrasound increased significantly (15.6 +/- 7.7% to 22.5 +/- 12.3%, p = 0.0002), resulting in a significant inverse correlation between epicardial physiology and anatomy (r = -0.58, p <0.0001). The IMR was lower in these patients compared with those > or =2 years after HT (24.1 +/- 14.3 vs 29.4 +/- 18.8 units, p = 0.05), suggesting later spread of CAV to the microvasculature. As the IMR increased, fractional flow reserve increased (0.86 +/- 0.06 to 0.90 +/- 0.06, p = 0.0035 comparing recipients with IMRs < or =20 to those with IMRs > or =40), despite no difference in percentage plaque volume (21.0 +/- 11.2% vs 20.5 +/- 10.5%, p = NS). In conclusion, early after HT, anatomic and physiologic evidence of epicardial CAV was found. Later after HT, the physiologic effect of epicardial CAV may be less, because of increased microvascular dysfunction.
The American Journal of Cardiology 06/2007; 99(11):1603-7. DOI:10.1016/j.amjcard.2007.01.039 · 3.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: As heart disease is increasingly recognized in women and as important studies have elucidated the benefit of implantable cardioverter defibrillators (ICDs) in patients with nonischemic cardiomyopathy (NICM), little is known regarding the effect of gender difference on arrhythmic risk in this population. We sought to determine if there are gender differences in arrhythmic risk and potential defibrillator benefit in patients with NICM.
The records of 767 consecutive patients who underwent ICD implant at the Stanford Medical Center from 1984 to 2002 were reviewed. Only patients with NICM were considered (n = 201, 26.2%). Of these, 140 patients had clinical follow-up information available. Baseline variables were examined, including age, baseline heart rate, ejection fraction, and medications. We evaluated the time to first shock as well as all-cause mortality in this patient population. Kaplan-Meier survival curves were plotted, a log-rank test was used to evaluate significance, and Cox-proportional hazards test was used for multivariate analysis.
There were 88 (62.9%) men and 52 (37.1%) women. Between male and female patients, there were no significant differences in baseline mean age (54.8 +/- 1.9 years vs 53.1 +/- 2.3 years, respectively), ejection fraction (35.2 +/- 2.0% vs 33.3 +/- 2.3%, respectively), and mean left ventricular end-diastolic dimension (6.4 +/- 0.3 cm vs 5.9 +/- 0.2 cm, respectively). Mean follow-up time was 30.8 months. Thirty-two male patients (36.4 +/- 0.05%) received appropriate shocks compared with 20 female patients (38.5 +/- 0.07%). Mean time to the first appropriate shock was 11.9 +/- 3.9 months for male patients and 21.3 +/- 5.8 months for female patients (P = 0.2). Nineteen male patients (21.6 +/- 0.05%) died or received heart transplant during the follow-up period compared with 6 female patients (11.5 +/- 0.04%) (P = 0.11).
Male and female patients with NICM who received ICDs had similar rate of appropriate shock and mortality. In this population gender does not appear to be an important risk factor for mortality or arrhythmic events.
[Show abstract][Hide abstract] ABSTRACT: Spontaneous coronary artery dissection (SCAD) is a potentially life-threatening entity with a variety of clinical presentations. We report a patient who presented with chest pain and angiographic evidence of coronary dissection. Due to the rapid resolution of symptoms and benign-appearing nature of the dissection, no intervention was pursued and the patient was maintained on medical therapy. She represented 2 days later with substernal chest pain, dynamic EKG changes, positive cardiac biomarkers and a transient depression of her left ventricular function.
International journal of cardiology 04/2007; 116(2):e48-50. DOI:10.1016/j.ijcard.2006.06.024 · 6.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Incidental cardiac irradiation during treatment of thoracic neoplasms has increased risks for subsequent acute myocardial infarction or sudden cardiac death. Identifying patients who have a high risk for a coronary event may decrease morbidity and mortality. The objective of this study was to evaluate whether stress imaging can identify severe, unsuspected coronary stenoses in patients who had prior mediastinal irradiation for Hodgkin's disease.
We enrolled 294 outpatients observed at a tertiary care cancer treatment center after mediastinal irradiation doses 35 Gy for Hodgkin's disease who had no known ischemic cardiac disease. Patients underwent stress echocardiography and radionuclide perfusion imaging at one stress session. Coronary angiography was performed at the discretion of the physician.
Among the 294 participants, 63 (21.4%) had abnormal ventricular images at rest, suggesting prior myocardial injury. During stress testing, 42 patients (14%) developed perfusion defects (n = 26), impaired wall motion (n = 8), or both abnormalities (n = 8). Coronary angiography showed stenosis 50% in 22 patients (55%), less than 50% in nine patients (22.5%), and no stenosis in nine patients (22.5%). Screening led to bypass graft surgery in seven patients. Twenty-three patients developed coronary events during a median of 6.5 years of follow-up, with 10 acute myocardial infarctions (two fatal).
Stress-induced signs of ischemia and significant coronary artery disease are highly prevalent after mediastinal irradiation in young patients. Stress testing identifies asymptomatic individuals at high risk for acute myocardial infarction or sudden cardiac death.
[Show abstract][Hide abstract] ABSTRACT: While pharmaceutical innovation has been highly successful in reducing mortality in chronic heart failure, this has not been matched by similar success in decompensated heart failure syndromes. Despite outstanding issues over definitions and end points, we argue in this paper that an unprecedented wealth of pharmacologic innovation may soon transform the management of these challenging patients. Agents that target contractility, such as cardiac myosin activators and novel adenosine triphosphate-dependent transmembrane sodium-potassium pump inhibitors, provide inotropic support without arrhythmogenic increases in cytosolic calcium or side effects of more traditional agents. Adenosine receptor blockade may improve glomerular filtration and diuresis by exerting a direct beneficial effect on glomerular blood flow while vasopressin antagonists promote free water excretion without compromising renal function and may simultaneously inhibit myocardial remodeling. Urodilatin, the renally synthesized isoform of atrial natriuretic peptide, may improve pulmonary congestion via vasodilation and enhanced diuresis. Finally, metabolic modulators such as perhexiline may optimize myocardial energy utilization by shifting adenosine triphosphate production from free fatty acids to glucose, a unique and conceptually appealing approach to the management of heart failure. These advances allow optimism not only for the advancement of our understanding and management of decompensated heart failure syndromes but for the translational research effort in heart failure biology in general.
Journal of the American College of Cardiology 01/2007; 48(12):2397-409. DOI:10.1016/j.jacc.2006.08.039 · 15.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 28-year-old man presented at hospital with persistent pain in his chest and left arm, a paced rhythm on electrocardiography and elevated levels of cardiac enzymes. He was known to have patent foramen ovale and a dual-chamber pacemaker, which had been implanted following electrophysiological ablation to treat supraventricular tachycardia 3 years previously. The patient did not have a history of cardiovascular risk factors, recent travel, immobilization or clinical features of infection, and he was not taking any medication.
Electrocardiography, cardiac enzyme studies, coronary angiography and transthoracic echocardiography.
Acute myocardial infarction, paradoxical coronary embolus and patent foramen ovale.
Coronary aspiration embolectomy and systemic anticoagulation.
Nature Clinical Practice Cardiovascular Medicine 12/2006; 3(11):633-6. DOI:10.1038/ncpcardio0681 · 7.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Investigating changes in coronary physiology that occur after cardiac transplantation has been challenging. Simultaneous and independent assessment of the epicardial artery by measuring fractional flow reserve (FFR) and of the microvasculature by calculating the index of microvascular resistance (IMR) with a single coronary pressure wire may be useful.
Twenty-five asymptomatic patients with normal coronary angiograms underwent FFR, thermodilution-derived IMR and coronary flow reserve (CFR) and intravascular ultrasound (IVUS) evaluation soon after cardiac transplantation and 1 year later.
FFR significantly worsened (0.90 +/- 0.05 at baseline to 0.85 +/- 0.06 at 1 year, p = 0.004). FFR correlated strongly with percent plaque volume as measured by IVUS (r = -0.58, p < 0.0001). IMR improved significantly (29.2 +/- 15.9 at baseline to 19.3 +/- 7.6 units at 1 year, p = 0.007). CFR increased, but not significantly (2.6 +/- 1.4 at baseline to 3.2 +/- 1.2 at 1 year, p = not significant). Diabetes and donor heart ischemic time independently predicted baseline IMR. Treatment with rapamycin independently predicted FFR at 1 year.
New coronary physiologic measures, FFR and IMR, show that epicardial artery physiology worsens and correlates with anatomic changes, whereas microvascular physiology improves during the first year after cardiac transplantation. CFR, the traditional method for evaluating coronary circulatory physiology, did not identify these changes.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 08/2006; 25(7):765-71. DOI:10.1016/j.healun.2006.03.003 · 5.61 Impact Factor