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ABSTRACT: N-Terminal pro-brain natriuretic peptide (NT-proBNP) and cardiopulmonary exercise testing (CPET)-derived variables are gold standards for assessing prognosis in heart failure (HF) patients. We sought to refine cardiac events prediction by performing a combined analysis of NT-proBNP with markers of exercise ventilatory efficiency.
A total of 260 stable HF patients underwent measurements of plasma NT-proBNP levels before, at peak exercise, and at 1-minute CPET recovery phase along with peak oxygen uptake (VO(2)), ventilation to CO(2) production (VE/VCO(2)) slope, and exercise periodic breathing (EPB) determinations. After a median follow-up period of 20.6 months, there were 54 cardiac-related deaths. Univariate analysis including NT-proBNP at rest, at peak exercise, and at 1 minute recovery, peak VO(2), VE/VCO(2) slope, and EPB showed NT-proBNP to be the strongest independent predictor with equivalent performance for rest, peak, and recovery levels. Thus, only NT-proBNP at rest was considered (Harrel C 0.783, 95% confidence interval [CI] 0.722-0.844) with VE/VCO(2) slope (Harrel C 0.720, 95% CI 0.646-0.794), EPB (Harrel C 0.685, 95% CI 0.619-0.751), and peak VO(2) (Harrel C 0.618, 95% CI 0.533-0.704). With bivariate stepwise analyses, NT-proBNP along with EPB emerged as the strongest prognosticators (Harrel C 0.800, 95% CI 0.737-0.862).
In the refinement for robust outcome predictors in HF patients, NT-proBNP levels together with EPB led to the most powerful definition. VE/VCO(2) slope and peak VO(2) did not provide any prognostic adjunct. A biomarker/CPET approach seems very promising to warrant the continuous implementation in the prognostic work-up of HF patients.
Journal of cardiac failure 04/2012; 18(4):313-20. · 3.25 Impact Factor
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ABSTRACT: The cardiovascular component associated with chronic obstructive pulmonary disease (COPD) plays a major role in disease prognosis, accounting for 25% of the deaths. Experimental and initial clinical data suggest that beta-adrenergic agonists accelerate fluid clearance from the alveolar airspace, with potentially positive effects on cardiogenic and noncardiogenic pulmonary oedema. This pilot study investigated the acute effects of the long-acting beta-2 agonist, salmeterol, on alveolar fluid clearance after rapid saline intravenous infusion by evaluating diffusive and mechanical lung properties. Ten COPD and 10 healthy subjects were treated with salmeterol or placebo 4 h before the patient's mechanical and diffusive lung properties were measured during four non consecutive days, just before and after a rapid saline infusion, or during a similar period without an infusion. RESULTS: In both COPD and healthy subjects, rapid saline infusion with placebo or salmeterol premedication lead to a significant decrease in diffusion capacity for carbon monoxide (DLCO) and forced expiratory volume in 1 s (FEV1). Nonetheless, salmeterol pretreatment lead to a significantly reduced gas exchange impairment caused by saline infusion (-64% of DLCO reduction compared with placebo), whereas it did not affect changes in FEV1. In the control setting with no infusion, we found no significant change in either DLCO or mechanical properties of the lung. CONCLUSIONS: Salmeterol appears to provide a protective effect, not related to bronchodilation, against an acute alveolar fluid clearance challenge secondary to lung fluid overload in COPD patients.
Pulmonary Pharmacology & Therapeutics 02/2012; 25(1):119-23. · 2.80 Impact Factor
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International journal of cardiology 12/2011; 154(3):384-5. · 7.08 Impact Factor
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International journal of cardiology 12/2011; 153(2):213-4. · 7.08 Impact Factor
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ABSTRACT: Exercise oscillatory breathing (EOB) is a ventilatory abnormality that occurs in ∼20% of heart failure (HF) patients and carries a very unfavourable prognosis. Pulmonary vasoconstriction has been suggested to be involved in this disorder. We hypothesized that modulation of pulmonary vascular hypertone by oversignalling of the nitric oxide pathway with phosphodiesterase 5 (PDE5) inhibition might be beneficial. Accordingly, we performed a 1-year pilot trial with sildenafil in patients with HF and EOB.
Among 122 HF cases, 32 presented with EOB during cardiopulmonary exercise testing (CPX) and were randomized to receive placebo (n = 16) or sildenafil (n = 16) at the dose of 50 mg three times a day, in addition to their current antifailure treatment. CPX-derived variables and pulmonary haemodynamics were assessed at 6 and 12 months. Sildenafil reversed EOB in 87% of patients at 6 months and 93% at 1 year, respectively (P < 0.01). This effect was accompanied by an improvement in functional performance (peak VO(2); from 9.6 to 12.4 and 13.2 mL/min/kg; P < 0.01) and exercise ventilation efficiency (ventilation to CO(2) production slope; from 41.1 to 32.7 and 31.5; P < 0.01). Chronic treatment with PDE5 inhibition significantly decreased pulmonary capillary wedge pressure (from 21 to 14 and 14 mmHg), mean pulmonary artery pressure (PAP; from 34.8 to 23 and 24 mmHg), and pulmonary vascular resistance (PVR; from 360 to 270 and 266 dyne/s/cm(5)) compared with placebo (P < 0.01 for each comparison). On exploratory analysis, there was a correlation between PAP and PVR and the decrease in EOB in the treatment group. Placebo did not alter any of the aforementioned variables.
PDE5 inhibition in HF patients with EOB offers the dual advantage of improving functional capacity and modulating the EOB pattern. PAP and PVR reduction seem to underlie the correction of the breathing disorder. Whether reversal of this unfavourable prognostic signal can affect survival remains unconfirmed at the moment.
European Journal of Heart Failure 11/2011; 14(1):82-90. · 4.90 Impact Factor
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ABSTRACT: Previous research has demonstrated the prognostic value of cardiopulmonary exercise testing (CPX) in elderly patients with heart failure (HF). Investigations that have comprehensively examined the value of CPX across different age groups are lacking. The purpose of the present investigation was to evaluate the prognostic value of CPX in young, middle-aged and older patients with HF.
A total of 1605 subjects (age: 59.2 ± 13.7 years, 78% male) underwent CPX and were subsequently tracked for major cardiac events. Ventilatory efficiency (VE/VCO(2) slope) and peak oxygen consumption (VO(2)), both absolute and percent-predicted, were determined. The prognostic value of these CPX variables was assessed in ≤ 45, 46-65 and ≥ 66 year subgroups.
The three year event rates for major cardiac events in the ≤ 45, 46-65 and ≥ 66 year subgroups were 8.8%, 6.0% and 5.7%, respectively. The VE/VCO(2) slope (Hazard ratio ≥ 1.07, p<0.001), peak VO(2) (Hazard ratio ≤ 0.87, p<0.001) and percent-predicted peak VO(2) (Hazard ratio 0 ≤ 0.98, p<0.001) were all significant prognostic markers in each age subgroup. While the VE/VCO(2) slope carried the greatest prognostic strength, peak VO(2) and percent-predicted peak VO(2) were retained in multivariate analyses (Residual Chi-Square ≥ 5.2, p<0.05). With respect to peak VO(2), the actual value was the more robust prognostic marker in the ≤ 45 and ≥ 66 year subgroups while the percent-predicted expression provided better predictive resolution in subjects who were 46-65 years old.
These results indicate that, irrespective of a patient's age at presentation, CPX provides valuable prognostic information in the HF population.
International journal of cardiology 09/2011; 151(3):278-83. · 7.08 Impact Factor
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ABSTRACT: 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.
Circulation 06/2011; 124(2):164-74. · 14.74 Impact Factor
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ABSTRACT: Despite advances in the treatment of heart failure (HF), which have resulted in improved survival, overall prognosis continues to be poor. Given the high short-term mortality rate, it remains important to utilize assessment techniques with established prognostic value in this patient population. Ideally, a given assessment should also be able to accurately reflect disease severity, a heterogeneous phenomenon in patients with HF, and accurately reflect the magnitude of physiologic/clinical improvement following the implementation or titration of an intervention. Cardiopulmonary exercise testing (CPX) satisfies all of the aforementioned desirable assessment attributes. Peak oxygen consumption and the minute ventilation/carbon dioxide production slope are key CPX variables in assessing prognosis and gauging disease severity. Given the high value of information obtained from this procedure, CPX should be considered a core assessment in the HF population. The current review will concisely define key CPX variables and summarize their clinical applications in patients with HF.
Congestive Heart Failure 05/2011; 17(3):115-9.
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ABSTRACT: The assessment of patients with suspected or confirmed pulmonary arterial hypertension (PAH) and secondary pulmonary hypertension (PH) continues to evolve and, in recent years, evidence demonstrating that cardiopulmonary exercise testing (CPX) provides valuable information has grown at an impressive rate. The key premise supporting the use of CPX is that certain variables obtained provide insight into the degree of ventilation/perfusion mismatching secondary to altered pulmonary hemodynamics. In this article, we discuss the pathophysiology of PAH and secondary PH and its impact on cardiac function, review the clinical presentation of patients with elevated pulmonary pressures and outline a case for the use of CPX as an integral assessment technique, discuss CPX technology and testing procedures, and review the current state of available evidence and provide clinical recommendations for CPX in the setting of known or suspected PAH and secondary PH.
Expert Review of Respiratory Medicine 04/2011; 5(2):281-93.
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ABSTRACT: The prognostic value of exercise oscillatory breathing (EOB) during cardiopulmonary test (CPX) has been described in young chronic heart failure (HF) patients. We assessed the prognostic role of EOB vs other clinical and ventilatory parameters in elderly HF patients performing a maximal CPX. METHODS AND RESULTS: We prospectively followed-up 370 HF outpatients ≥ 65 years after a symptom limited CPX. We tested the predictive value of clinical and ventilatory parameters for all-cause mortality and a composite of all-cause mortality and HF hospitalizations. Median age was 74 years, 51% had ischemic heart disease, 25% NYHA class III; ejection fraction was 41% [34-50]. Peak oxygen consumption (PVO(2)) was 11.9 [9.9-14] mL/kg/min, the slope of the regression line relating ventilation to CO(2) output, (VE/VCO(2) slope) was 33.9 [29.8-39.2]. EOB was found in 58% of patients. At follow-up, 84 patients died and overall 158, using a time-to-first event approach, met the composite end-point. Independent predictors of all-cause mortality were CPX EOB and the ratio of VE/VCO(2) slope to peak VO(2), hemoglobin, creatinine and body mass index. The area under the ROC curve (AUC) of the Cox multivariable model was 0.80 (95% CI 0.73 to 0.87). Independent predictors of the composite end-point were EOB, VE/VCO(2) slope, hemoglobin and HF admissions in the previous year (Model AUC 0.75) (95% CI 0.69 to 0.81). CONCLUSIONS: Among elderly HF patients, EOB prevalence is higher than middle-aged cohorts. EOB and the ratio of VE/VCO(2) slope to peak VO(2) resulted the strongest ventilatory predictor of all-cause mortality, independent of ventricular function.
International journal of cardiology 03/2011; 155(1):115-9. · 7.08 Impact Factor
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ABSTRACT: Cardiopulmonary exercise testing (CPX) is a specialized exercise assessment that provides valuable information in a number of patient populations. Physicians are often familiar with standard exercise testing procedures (i.e., the cardiac stress test) and, therefore, appropriately refer patients with signs/symptoms suggestive of myocardial ischemia. However, the procedures surrounding referral for CPX, and the relevance of the data obtained, may not be as widely understood in the medical community. The purpose of the current special report is to provide physicians referring patients for CPX with information on the appropriateness of CPX referral and testing logistics, the identification of an appropriate CPX laboratory for referral, and definitions on key CPX variables that should be included in the final report.
Future Cardiology 01/2011; 7(1):55-60.
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ABSTRACT: Although chronic hypoxia is a claimed myocardial risk factor reducing tolerance to ischemia/reperfusion (I/R), intermittent reoxygenation has beneficial effects and enhances heart tolerance to I/R. AIM OF THE STUDY: To test the hypothesis that, by mimicking intermittent reoxygenation, selective inhibition of phosphodiesterase-5 activity improves ischemia tolerance during hypoxia. Adult male Sprague-Dawley rats were exposed to hypoxia for 15 days (10% O₂) and treated with placebo, sildenafil (1.4 mg/kg/day, i. p.), intermittent reoxygenation (1 h/day exposure to room air) or both. Controls were normoxic hearts. To assess tolerance to I/R all hearts were subjected to 30-min regional ischemia by left anterior descending coronary artery ligation followed by 3 h-reperfusion. Whereas hypoxia depressed tolerance to I/R, both sildenafil and intermittent reoxygenation reduced the infarct size without exhibiting cumulative effects. The changes in myocardial cGMP, apoptosis (DNA fragmentation), caspase-3 activity (alternative marker for cardiomyocyte apoptosis), eNOS phosphorylation and Akt activity paralleled the changes in cardioprotection. However, the level of plasma nitrates and nitrites was higher in the sildenafil+intermittent reoxygenation than sildenafil and intermittent reoxygenation groups, whereas total eNOS and Akt proteins were unchanged throughout. CONCLUSIONS: Sildenafil administration has the potential to mimic the cardioprotective effects led by intermittent reoxygenation, thereby opening the possibility to treat patients unable to be reoxygenated through a pharmacological modulation of NO-dependent mechanisms.
PLoS ONE 01/2011; 6(11):e27910. · 4.09 Impact Factor
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Massimo F Piepoli, Marco Guazzi,
Giuseppe Boriani,
Mariantonietta Cicoira,
Ugo Corrà,
Luciano Dalla Libera,
Michele Emdin,
Donato Mele,
Claudio Passino,
Giorgio Vescovo,
Carlo Vigorito,
Giovanni Q Villani,
Piergiuseppe Agostoni
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ABSTRACT: Muscular fatigue and dyspnoea on exertion are among the most common symptoms in chronic heart failure; however their origin is still poorly understood. Several studies have shown that cardiac dysfunction alone cannot fully explain their origin, but the contribution of the multiorgan failure present in this syndrome must be highlighted. In this study, divided in two parts (see part II: pp. 643–648), we aimed to summarize the existing evidence and the most controversial aspects of the complex interplay of different factors involved in symptom generation. In this first part of the review, six key factors are revised: the heart, the lung, the skeletal muscle, the hormonal changes, the O2 delivery to the periphery, the endothelium. In the second part, the role of the excitatory reflexes and the cardiac cachexia will be presented, and finally, the potential therapeutic implications are discussed. We believe that a better knowledge of the pathophysiology of this syndrome may contribute to the management of the patients and to the improvement in their stress tolerance and quality of life.
European journal of cardiovascular prevention and rehabilitation: official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology 12/2010; 17(6):637-42. · 2.51 Impact Factor
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Massimo F Piepoli, Marco Guazzi,
Giuseppe Boriani,
Mariantonietta Cicoira,
Ugo Corrà,
Luciano Dalla Libera,
Michele Emdin,
Donato Mele,
Claudio Passino,
Giorgio Vescovo,
Carlo Vigorito,
Giovanni Villani,
Piergiuseppe Agostoni
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ABSTRACT: Muscular fatigue and dyspnoea on exertion are among the most common symptoms in chronic heart failure; however their origin is still poorly understood. Several studies have shown that cardiac dysfunction alone cannot fully explain their origin, but the contribution of the multiorgan failure present in this syndrome must be highlighted. We aimed to summarize the existing evidence and the most controversial aspects of the complex interplay of different factors involved in the symptom generation. In the first part of the review, six key factors were revised (the heart, the lung, the skeletal muscle, the hormonal changes, the O2 delivery to the periphery, the endothelium). In this second part, the role of the excitatory reflexes and the cardiac cachexia are presented. Finally, potential therapeutic implications are discussed here. We believe that a better knowledge of the pathophysiology of this syndrome may contribute to the management of the patients and to the improvement in their stress tolerance and quality of life.
European journal of cardiovascular prevention and rehabilitation: official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology 12/2010; 17(6):643-8. · 2.51 Impact Factor
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ABSTRACT: Cardiopulmonary exercise testing (CPX) is a relatively old technology, but has sustained relevance for many primary care clinical scenarios in which it is, ironically, rarely considered. Advancing computer technology has made CPX easier to administer and interpret at a time when our aging population is more prone to comorbidities and higher prevalence of nonspecific symptoms of exercise intolerance and dyspnea, for which CPX is particularly useful diagnostically and prognostically. These discrepancies in application are compounded by patterns in which CPX is often administered and interpreted by cardiology, pulmonary, or exercise specialists who limit their assessments to the priorities of their own discipline, thereby missing opportunities to distinguish symptom origins. When used properly, CPX enables the physician to assess fitness and uncover cardiopulmonary issues at earlier phases of work-up, which would therefore be especially useful for primary care physicians. In this article, we provide an overview of CPX principles and testing logistics, as well as some of the clinical contexts in which it can enhance patient care.
Postgraduate Medicine 11/2010; 122(6):68-86. · 1.78 Impact Factor
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ABSTRACT: Peak oxygen consumption derived from cardiopulmonary exercise (CPX) testing provides important prognostic information in patients with heart failure (HF). The oxygen consumption at the ventilatory threshold (VT) has also been shown to be prognostic. However, the VT cannot always be detected in patients with HF. Other variables such as the difference between peak oxygen consumption and oxygen consumption at the VT (termed the functional aerobic reserve [FAR]) may also provide prognostic information. The purpose of this study was to determine the prognostic value of an undetectable VT and FAR.
Eight hundred seventy-four patients with chronic, systolic HF (70% male, age 54 ± 14 years, ejection fraction 29% ± 12%) underwent CPX and were tracked for 2 years for major events (death, transplant, and left ventricular assist device implantation).
Patients were divided into 2 subgroups based on whether VT could be detected or not. There were 141 major events during the 2-year follow-up. Kaplan-Meier analysis for the 2 VT subgroups demonstrated worse prognoses for patients with a nondetectable VT versus those with a detectable VT (P < .001). Based on receiver operating characteristic curve analysis (FAR = 0 mlO₂ kg⁻¹ min⁻¹ for patients with undetectable VT), the optimal cut-point for FAR was ≤/>3 mlO₂ kg min⁻¹ (sensitivity/specificity 69%/60%). Cox regression analysis identified the FAR as a significant univariate predictor of risk and was retained in multivariate analysis.
In conclusion, these data reveal that an undetectable VT and the FAR during CPX testing can provide useful prognostic information in patients with HF.
American heart journal 11/2010; 160(5):922-7. · 4.65 Impact Factor
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ABSTRACT: The assessment of aerobic exercise capacity is an important component in the clinical management of patients with heart failure (HF). Although a significant percentage of patients diagnosed with HF also present with chronic obstructive pulmonary disease (COPD) comorbidity, the combined impact of these chronic conditions on the aerobic exercise response is unknown and is therefore the purpose of the present investigation.
Sixty-nine subjects with HF and COPD were matched to 69 subjects solely diagnosed with HF according to age, sex, and HF etiology. All subjects underwent resting pulmonary function and diffusion capacity testing, echocardiography with tissue Doppler imaging, and cardiopulmonary exercise testing (CPX).
Subjects with COPD comorbidity had significantly lower pulmonary function testing and diffusion capacity values versus HF alone (P < .05). In addition, subjects with both HF and COPD had significantly higher pulmonary artery systolic pressures (51.9 ± 9.0 vs 37.0 ± 7.8 mm Hg, P < .001) as assessed by pulsed Doppler echocardiography. Cardiopulmonary exercise testing revealed a significantly poorer response in subjects with HF and COPD by all variables that were analyzed, including peak oxygen consumption (12.1 ± 4.3 vs 16.3 ± 4.3 mL kg⁻¹ min⁻¹, P < .001), minute ventilation/carbon dioxide production slope (42.7 ± 7.4 vs 33.3 ± 6.6, P < .001) and heart rate recovery at 1 minute (12.1 ± 2.5 vs 14.2 ± 2.9 beats, P < .001).
Patients with HF and the comorbidity of COPD have significantly impaired CPX responses. This novel finding may impact the clinical interpretation of CPX data in patients with HF who also present with this chronic pulmonary condition.
American heart journal 11/2010; 160(5):900-5. · 4.65 Impact Factor
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ABSTRACT: In heart failure (HF), a defective nitric oxide signaling is involved in left ventricular (LV) diastolic abnormalities and remodeling. PDE5 inhibition, by blocking degradation of nitric oxide second-messenger cyclic guanosine monophosphate, might be beneficial. In a cohort of systolic HF patients, we tested the effects of PDE5 inhibition (sildenafil) on LV ejection fraction, diastolic function, cardiac geometry, and clinical status.
Forty-five HF patients (New York Heart Association class II-III) were randomly assigned to placebo or sildenafil (50 mg three times per day) for 1 year, with assessment (6 months and 1 year) of LV ejection fraction, diastolic function, geometry, cardiopulmonary exercise performance, and quality of life. In the sildenafil group only, at 6 months and 1 year, LV ejection fraction, early diastolic tissue Doppler velocities (E') at the mitral lateral (from 4.62 to 5.20 and 5.19 m/s) and septal (from 4.71 to 5.23 and 5.24 m/s) annuli significantly increased, whereas the ratio of early transmitral (E) to E' lateral decreased (from 13.1 to 9.8 to 9.4) (P<0.01). Changes were accompanied by a reverse remodeling of left atrial volume index (from 32.0 to 29.0 and 29.1 mL/m(2); P<0.01) and LV mass index (from 148.0 to 130.0 and 128.0 g/m(2); P<0.01). Furthermore, sildenafil improved exercise performance (peak Vo(2)), ventilation efficiency (ventilation to CO(2) production slope), and quality of life (P<0.01). Minor adverse effects were noted: flushing in 4 and headache in 2 treated patients.
Findings confirm that in HF, sildenafil improves functional capacity and clinical status and provide the first human evidence that LV diastolic function and cardiac geometry are additional targets of benefits related to chronic PDE5 inhibition.
Circulation Heart Failure 10/2010; 4(1):8-17. · 6.29 Impact Factor
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ABSTRACT: Cardiopulmonary exercise testing (CPET) provides powerful information on risk of death in heart failure (HF). We sought to define the relative and additive contribution of the 3 landmark (CPET) prognostic markers--peak oxygen consumption (VO₂), minute ventilation/carbon dioxide production (VE/VCO₂) slope, and exercise periodic breathing (EPB)-to the overall risk of cardiac death and to develop a prognostic score for optimizing risk stratification in HF patients.
A total of 695 stable HF patients (average LVEF: 25 ± 8%) underwent a symptom-limited CPET maximum test after familiarization and were prospectively tracked for cardiac mortality. At multivariable Cox analysis EPB emerged as the strongest prognosticator. Using a statistical bootstrap technique (5000 data resamplings), point estimates, and 95% confidence intervals were obtained. Thirty-two configurations were adopted to classify patients into a given cell, according to EPB presence or absence and values of the 2 other covariates. Configurations without EPB and with VE/VCO₂ slope ≤30 were not significantly different from 0 (reference value). Statistical power of configurations increased with higher VE/VCO₂ slope and lower peak VO₂. This prompted us to formulate a score including EPB as a discriminating variable, the (P)e(R)i(O)dic (B)reathing during (E)xercise (PROBE), which ranges between -1 and 1, with zero as reference configuration, that would help to optimize the prognostic accuracy of CPET-derived variables. The greatest PROBE score impact was provided by EPB, followed by VE/VCO₂ slope, whereas peak VO₂ added minimal prognostic power.
EPB with an elevated VE/VCO₂ slope leads to the highest and most precise PROBE score, whereas no additional risk information emerges when EPB is present with a peak VO₂ ≤10 mL O₂·kg⁻¹·min⁻¹. PROBE score appears to provide a step forward for optimizing CPET use in HF prognostic definition.
Journal of cardiac failure 10/2010; 16(10):799-805. · 3.25 Impact Factor
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ABSTRACT: 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.
Nature Reviews Cardiology 10/2010; 7(11):648-59. · 8.83 Impact Factor
