Long-Term Use of Sildenafil in the Therapeutic Management of Heart Failure Marco Guazzi, Michele Samaja, Ross Arena, Marco Vicenzi, Maurizio D. Guazzi We tested whether chronic phosphodiesterase 5 ...inhibition by sildenafil is beneficial in heart failure. A total of 46 heart failure patients were randomly assigned to placebo (23 patients) or sildenafil (23 patients), with 3- and 6-month assessments of cardiopulmonary exercise test performance, brachial artery flow-mediated maximal dilatation, and ergoreflex responses. Sildenafil and not placebo improved flow-mediated maximal dilatation, ergoreflex effect on ventilation, exercise ventilation to CO2 production slope, and breathlessness, at both 3 and 6 months (p < 0.01). Findings suggest that benefits of sildenafil in heart failure are sustained and that an endothelium-mediated modulation of the muscle ergoreflex oversignaling may be at work.
Background Increased slope of exercise ventilation to carbon dioxide production (VE/VCO2 ) is an established prognosticator in patients with heart failure. Recently, the occurrence of exercise ...oscillatory breathing (EOB) has emerged as an additional strong indicator of survival. Objective The aim of this study is to define the respective prognostic significance of these variables and whether excess risk may be identified when either respiratory disorder is present. Methods In 288 stable chronic HF patients (average left ventricular ejection fraction, 33 ± 13%) who underwent cardiopulmonary exercise testing, the prognostic relevance of VE/VCO2 slope, EOB, and peak V o2 was evaluated by multivariate Cox regression. Results During a mean interval of 28 ± 13 months, 62 patients died of cardiac reasons. Thirty-five percent presented with EOB. Among patients exhibiting EOB, 54% had an elevated VE/VCO2 slope. The optimal threshold value for the VE/VCO2 slope identified by receiver operating characteristic analysis was <36.2 or ≥36.2 (sensitivity, 77%; specificity, 64%; P < .001). Univariate predictors of death included low left ventricular ejection fraction, low peak V o2 , high VE/VCO2 slope, and EOB presence. Multivariate analysis selected EOB as the strongest predictor (χ2 , 46.5; P < .001). The VE/VCO2 slope (threshold, <36.2 or ≥36.2) was the only other exercise test variable retained in the regression (residual χ2 , 5.9; P = .02). The hazard ratio for subjects with EOB and a VE/VCO2 slope ≥36.2 was 11.4 (95% confidence interval, 4.9-26.5; P < .001). Conclusion These findings identify EOB as a strong survival predictor even more powerful than VE/VCO2 slope. Exercise oscillatory breathing presence does not necessarily imply an elevated VE/VCO2 slope, but combination of either both yields to a burden of risk remarkably high.
Pulmonary Hypertension in Heart Failure Guazzi, Marco, MD, PhD; Naeije, Robert, MD, PhD
Journal of the American College of Cardiology,
04/2017, Letnik:
69, Številka:
13
Journal Article
Recenzirano
Odprti dostop
Abstract Pulmonary hypertension is a common hemodynamic complication of heart failure. Interest in left-sided pulmonary hypertension has increased remarkably in recent years because its development ...and consequences for the right heart are now seen as mainstay abnormalities that begin in the early stages of the disease and bear unfavorable prognostic insights. However, some knowledge gaps limit our ability to influence this complex condition. Accordingly, attention is now focused on: 1) establishing a definitive consensus for a hemodynamic definition, perhaps incorporating exercise and fluid challenge; 2) implementing the limited data available on the pathobiology of lung capillaries and small arteries; 3) developing standard methods for assessing right ventricular function and, hopefully, its coupling to pulmonary circulation; and 4) searching for effective therapies that may benefit lung vessels and the remodeled right ventricle. The authors review the pathophysiology, pathobiology, and emerging clinical perspectives on pulmonary hypertension across the broad spectrum of heart failure stages.
Abstract Pulmonary hypertension (PH) in left heart disease, classified as group II, is the most common form of PH that occurs in approximately 60% of cases of reduced and preserved left ventricular ...ejection fraction. Although relatively much is known about hemodynamic stages (passive or reactive) and their consequences on the right ventricle (RV) there is no consensus on the best hemodynamic definition of group II PH. In addition, the main pathways that lead to lung capillary injury and impaired biology of small artery remodelling processes are largely unknown. Typical lung manifestations of an increased pulmonary pressure and progressive RV-pulmonary circulation uncoupling are an abnormal alveolar capillary gas diffusion, impaired lung mechanics (restriction), and exercise ventilation inefficiency. Of several classes of pulmonary vasodilators currently clinically available, oral phosphodiesterase 5 inhibition, because of its strong selectivity for targeting the cyclic guanosine monophosphate pathway in the pulmonary circulation, is increasingly emerging as an attractive opportunity to reach hemodynamic benefits, reverse capillary injury, and RV remodelling, and improve functional capacity. Guanylate cyclase stimulators offer an additional intriguing opportunity but the lack of selectivity and systemic effects might preclude some of the anticipated benefits on the pulmonary circulation. Future trials will determine whether new routes of pharmacologic strategy aimed at targeting lung structural and vascular remodelling might affect morbidity and mortality in left heart disease populations. We believe that this therapeutic goal rather than a pure hemodynamic effect might ultimately emerge as an important challenge for the clinician.
BACKGROUND Pulmonary hypertension, which is related to right ventricular (RV) failure, indicates a poor prognosis in heart failure (HF). Increased ventilatory response and exercise oscillatory ...ventilation (EOV) also have a negative impact. We hypothesized that the severity classification of HF and risk prediction could be improved by combining functional capacity with cardiopulmonary exercise testing (CPET) and RV-pulmonary circulation coupling, as evaluated by the tricuspid annular plane systolic excursion (TAPSE)-pulmonary artery systolic pressure (PASP) relationship. METHODS Four hundred fifty-nine patients with HF were assessed with Doppler echocardiography and CPET and were tracked for outcome. The subjects were followed for major cardiac events (cardiac mortality, left ventricular assist device implant, or heart transplant). Cox regression and Kaplan-Meier analyses were performed with TAPSE and PASP as individual measures that were then combined into a ratio form. RESULTS The TAPSE/PASP ratio (TAPSE/PASP) was the strongest predictor, whereas the New York Heart Association classification and EOV added predictive value. A four-quadrant group prediction risk was created based on TAPSE (< 16 mm or ≥ 16 mm) vs PASP (< 40 mm Hg or ≥ 40 mm Hg) thresholds and the CPET variables distribution as follows: group A (TAPSE > 16 mm and PASP < 40 mm Hg) presented the lowest risk (hazard ratio, 0.17) and best ventilation; group B exhibited a low risk (hazard ratio, 0.88) with depressed TAPSE (< 16 mm) and normal PASP, a preserved peak oxygen consumption ( o2 ), but high ventilation. Group C had an increased risk (hazard ratio, 1.3; TAPSE ≥ 16 mm, PASP ≥ 40 mm Hg), a reduced peak o2 , and a high EOV prevalence. Group D had the highest risk (hazard ratio, 5.6), the worse RV-pulmonary pressure coupling (TAPSE < 16 and PASP ≥ 40 mm Hg), the lowest peak o2 , and the highest EOV rate. CONCLUSIONS TAPSE/PASP, combined with exercise ventilation, provides relevant clinical and prognostic insights into HF. A low TAPSE/PASP with EOV identifies patients at a particularly high risk of cardiac events.
Abstract Objective To determine the impact of cardiorespiratory fitness (FIT) on survival in relation to the obesity paradox in patients with systolic heart failure (HF). Patients and Methods We ...studied 2066 patients with systolic HF (body mass index BMI ≥18.5 kg/m2 ) between April 1, 1993 and May 11, 2011 (with 1784 86% tested after January 31, 2000) from a multicenter cardiopulmonary exercise testing database who were followed for up to 5 years (mean ± SD, 25.0±17.5 months) to determine the impact of FIT (peak oxygen consumption <14 vs ≥14 mL O2 ∙ kg−1 ∙ min−1 ) on the obesity paradox. Results There were 212 deaths during follow-up (annual mortality, 4.5%). In patients with low FIT, annual mortality was 8.2% compared with 2.8% in those with high FIT ( P <.001). After adjusting for age and sex, BMI was a significant predictor of survival in the low FIT subgroup when expressed as a continuous ( P =.03) and dichotomous (<25.0 vs ≥25.0 kg/m2 ) ( P =.01) variable. Continuous and dichotomous BMI expressions were not significant predictors of survival in the overall and high FIT groups after adjusting for age and sex. In patients with low FIT, progressively worse survival was noted with BMI of 30.0 or greater, 25.0 to 29.9, and 18.5 to 24.9 (log-rank, 11.7; P =.003), whereas there was no obesity paradox noted in those with high FIT (log-rank, 1.72; P =.42). Conclusion These results indicate that FIT modifies the relationship between BMI and survival. Thus, assessing the obesity paradox in systolic HF may be misleading unless FIT is considered.
Objective Weaning from veno-arterial extracorporeal life support is challenging. The objective of this trial was to investigate the endothelial and hemodynamic effects of levosimendan in cardiogenic ...shock patients supported with veno-arterial extracorporeal life support. Design This was a prospective observational trial. Setting Cardiovascular intensive care unit of a large tertiary care university hospital in Monza, Italy. Participants and Interventions Flow-mediated dilatation of the brachial artery and hemodynamic parameters were assessed in 10 cardiogenic shock patients supported with veno-arterial extracorporeal life support, before and after the infusion of levosimendan. Measurements and Results Flow-mediated dilatation increased both as absolute value and as a percentage after levosimendan, from 0.10±0.12 to 0.61±0.21 mm (p<0.001) and from 3.2±4.2% to 17.8±10.4% (p<0.001), respectively. Cardiac index increased from 1.93±0.83 to 2.64±0.97 L/min/m2 (p = 0.008) while mixed venous oxygen saturation increased from 66.0% to 71.5% (p = 0.006) and arterial lactate levels decreased from 1.25 to 1.05 mmol/L (p = 0.004) without significant variations in arterial oxygen saturation or hemoglobin levels. This made it possible for clinicians to reduce extracorporeal membrane oxygenation blood flow from 1.92±0.65 to 1.12±0.49 L/min/m2 (p<0.001). Conclusion In conclusion, in the authors’ study population of adult cardiogenic shock patients supported with veno-arterial extracorporeal life support, their observations supported the use of levosimendan to improve endothelial function and hemodynamics and facilitate weaning from the extracorporeal support.
Objective The current understanding of pulmonary hypertension (PH) due to left heart diseases does not distinguish heart failure (HF) with reduced ejection fraction (HFrEF) from HF and preserved ...ejection fraction (HFpEF), in terms of pulmonary hemodynamics. The value of pulmonary vascular compliance (PCa) and diastolic pulmonary gradient (DPG) as predictors of survival in either HF syndrome is controversial. The aims of our study were to compare the pulmonary hemodynamics in the two HF phenotypes, given similar values of pulmonary artery wedge pressure (PAWP), and to evaluate the impact of PCa and DPG on survival. Methods We retrospectively reviewed the charts of 168 PH-HFrEF and 86 PH-HFpEF patients. The independent association of PCa and DPG with prognosis was assessed by means of a Cox proportional hazard model. All cause survival was analyzed over an average follow-up period of 50 months. Results PH-HFpEF patients had a significantly higher DPG than PH-HFrEF patients (6.1 ± 7.1 vs. 1.8 ± 4.5 mmHg, adjusted P = .025). PCa was similar in PH-HFpEF and PH-HFrEF. PCa was a significant predictor of survival, according to previously described preset cutoffs (2.15 mL/mmHg in HFrEF and 1.1 mL/mmHg in HFpEF) and based on a continuous scale; whereas DPG had no impact on survival in both patients groups. Conclusion Our findings suggest that for similar levels of PAWP, pulmonary circulation may be stiffer in patients with HFpEF-PH than patients with HFrEF-PH, leading to higher DPGs. Nonetheless, PCa rather than DPG emerged as the stronger predictor of survival in both left-sided PH phenotypes.
Abstract Background Recently, it has become increasingly recognized that pulmonary hypertension (PH) is a particularly ominous consequence of left-sided heart failure (HF). The primary aim of this ...investigation was to assess the ability of key cardiopulmonary exercise testing (CPX) variables to detect elevated pulmonary pressures in a HF cohort. Methods This was a retrospective analysis of a prospectively collected database. Two hundred ninety-three subjects with HF (63 ± 10 years old, 79% male) underwent Doppler echocardiography to estimate resting pulmonary artery systolic pressure (PASP). Peak oxygen consumption (VO2 ), the minute ventilation/carbon dioxide production (VE/VCO2 ) slope, peak partial pressure of end-tidal CO2 (PET CO2 ) and exercise oscillatory ventilation (EOV) were determined. Results Forty-six percent (n = 134) of the subjects presented with a PASP ≥40 mm Hg. A VE/VCO2 slope </≥36.0 was the best predictor of a PASP ≥40 mm Hg (odds ratio OR 12.1, 95% confidence interval CI 6.8–21.4; P < .001). Peak PET CO2 ≤34 mm Hg (OR 3.8, 95% CI 1.3–11.2; P < .001) and the presence of EOV (OR 3.2, 95% CI 1.8–5.8; P < .001) added significant diagnostic value. Conclusions Although CPX is an established prognostic assessment in the HF population, the results of the present investigation indicate that it may also have important diagnostic utility for PH.
Abstract Given the burden of cardiovascular disease (CVD), increasing the prevalence of healthy lifestyle choices is a global imperative. Currently, cardiac rehabilitation programs are a primary way ...that modifiable risk factors are addressed in the secondary prevention setting after a cardiovascular (CV) event/diagnosis. Even so, there is wide consensus that primary prevention of CVD is an effective and worthwhile pursuit. Moreover, continual engagement with individuals who have already been diagnosed as having CVD would be beneficial. Implementing health and wellness programs in the workplace allows for the opportunity to continually engage a group of individuals with the intent of effecting a positive and sustainable change in lifestyle choices. Current evidence indicates that health and wellness programs in the workplace provide numerous benefits with respect to altering CV risk factor profiles in apparently healthy individuals and in those at high risk for or already diagnosed as having CVD. This review presents the current body of evidence demonstrating the efficacy of worksite health and wellness programs and discusses key considerations for the development and implementation of such programs, whose primary intent is to reduce the incidence and prevalence of CVD and to prevent subsequent CV events. Supporting evidence for this review was obtained from PubMed, with no date limitations, using the following search terms: worksite health and wellness , employee health and wellness , employee health risk assessments , and return on investment . The choice of references to include in this review was based on study quality and relevance.
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