Alternatives to Transplantation in the Treatment of Heart Failure: New Diagnostic and Therapeutic Insights

none4siThe aim of our current special issue was to present a series of original researches and reviews on recent advances in the diagnosis, medical therapy, and surgical approaches of heart failure. As reported in the introductive review of Agnetti et al., cardiovascular disease is the leading cause of mortality in the US and in westernized countries with ischemic heart disease accounting for the majority of these deaths. Paradoxically, the improvements in the medical and surgical treatments of acute coronary syndromes are leading to an increasing number of “survivors” who are then developing heart failure. Despite considerable advances in its management, the gold standard for the treatment of end-stage heart failure patients remains heart transplantation. Nevertheless, this procedure can be o ered only to a small percentage of patients who could bene t from a new heart due to the limited availability of donor organs. e authors reported in this comprehensive review the evaluation of the safety and e cacy of innovative approaches in the diagnosis and treatment of patients refrac- tory to standard medical therapy and excluded from cardiac transplantation lists.mixedNicolini, Francesco; Piepoli, Massimo F.; Agnetti, Giulio; Siniscalchi, GiuseppeNicolini, Francesco; Piepoli, Massimo F.; Agnetti, Giulio; Siniscalchi, Giusepp

New Insights in the Diagnosis and Treatment of Heart Failure

Cardiovascular disease is the leading cause of mortality in the US and in westernized countries with ischemic heart disease accounting for the majority of these deaths. Paradoxically, the improvements in the medical and surgical treatments of acute coronary syndrome are leading to an increasing number of "survivors" who are then developing heart failure. Despite considerable advances in its management, the gold standard for the treatment of end-stage heart failure patients remains heart transplantation. Nevertheless, this procedure can be offered only to a small percentage of patients who could benefit from a new heart due to the limited availability of donor organs. The aim of this review is to evaluate the safety and efficacy of innovative approaches in the diagnosis and treatment of patients refractory to standard medical therapy and excluded from cardiac transplantation lists

Contribution of the lung to the genesis of cheyne-stokes respiration in heart failure: Plant gain beyond chemoreflex gain and circulation time

Background-The contribution of the lung or the plant gain (PG; ie, change in blood gases per unit change in ventilation) to Cheyne-Stokes respiration (CSR) in heart failure has only been hypothesized by mathematical models, but never been directly evaluated.Methods and Results-Twenty patients with systolic heart failure (age, 72.4 +/- 6.4 years; left ventricular ejection fraction, 31.5 +/- 5.8%), 10 with relevant CSR (24-hour apnea-hypopnea index [AHI] >= 10 events/h) and 10 without (AHI <10 events/h) at 24-hour cardiorespiratory monitoring underwent evaluation of chemoreflex gain (CG) to hypoxia (CG(O2)) and hypercapnia (CG(CO2)) by rebreathing technique, lung-to-finger circulation time, and PG assessment through a visual system. PG test was feasible and reproducible (intraclass correlation coefficient, 0.98; 95% CI, 0.91-0.99); the best-fitting curve to express the PG was a hyperbola (R-2 >= 0.98). Patients with CSR showed increased PG, CG(CO2) (but not CG(O2)), and lung-to-finger circulation time, compared with patients without CSR (all P<0.05). PG was the only predictor of the daytime AHI (R=0.56, P=0.01) and together with the CG(CO2) also predicted the nighttime AHI (R=0.81, P=0.0003) and the 24-hour AHI (R=0.71, P=0.001). Lung-to-finger circulation time was the only predictor of CSR cycle length (R=0.82, P=0.00006).Conclusions-PG is a powerful contributor of CSR and should be evaluated together with the CG and circulation time to individualize treatments aimed at stabilizing breathing in heart failure

The role of physical activity in individuals with cardiovascular risk factors: an opinion paper from Italian Society of Cardiology-Emilia Romagna-Marche and SIC-Sport

: Regular physical activity is a cornerstone in the prevention and treatment of atherosclerotic cardiovascular disease (CVD) due to its positive effects in reducing several cardiovascular risk factors. Current guidelines on CVD suggest for healthy adults to perform at least 150\u200amin/week of moderate intensity or 75\u200amin/week of vigorous intensity aerobic physical activity. The current review explores the effects of physical activity on some risk factors, specifically: diabetes, dyslipidemia, hypertension and hyperuricemia. Physical activity induces an improvement in insulin sensitivity and in glucose control independently of weight loss, which may further contribute to ameliorate both diabetes-associated defects. The benefits of adherence to physical activity have recently proven to extend beyond surrogate markers of metabolic syndrome and diabetes by reducing hard endpoints such as mortality. In recent years, obesity has greatly increased in all countries. Weight losses in these patients have been associated with improvements in many cardiometabolic risk factors. Strategies against obesity included caloric restriction, however greater results have been obtained with association of diet and physical activity. Similarly, the beneficial effect of training on blood pressure via its action on sympathetic activity and on other factors such as improvement of endothelial function and reduction of oxidative stress can have played a role in preventing hypertension development in active subjects. The main international guidelines on prevention of CVD suggest to encourage and to increase physical activity to improve lipid pattern, hypertension and others cardiovascular risk factor. An active action is required to the National Society of Cardiology together with the Italian Society of Sports Cardiology to improve the prescription of organized physical activity in patients with CVD and/or cardiovascular risk factors

What about chronotropic incompetence in heart failure with mildly reduced ejection fraction? Clinical and prognostic implications from the Metabolic Exercise combined with Cardiac and Kidney Indexes score dataset

Aims Chronotropic incompetence (CI) is a strong predictor of outcome in heart failure with reduced ejection fraction, however no data on its clinical and prognostic impacts in heart failure with mildly reduced ejection fraction (HFmrEF) are available. Therefore, the study aims to investigate, in a large multicentre HFmrEF cohort, the prevalence of CI as well as its relationship with exercise capacity and its prognostic role over the cardiopulmonary exercise testing (CPET) parameters. Methods and results Within the Metabolic Exercise combined with Cardiac and Kidney Indexes (MECKI) database, we analysed data of 864 HFmrEF out of 1164 stable outpatients who performed a maximal CPET at the cycle ergometer and who had no significant rhythm disorders or comorbidities. The primary study endpoint was cardiovascular (CV) death. All-cause death was also explored. Chronotropic incompetence prevalence differed depending on the method (peak heart rate, pHR% vs. pHR reserve, pHRR%) and the cut-off adopted (pHR% from ≤75% to ≤60% and pHRR% ≤ 65% to ≤50%), ranging from 11% to 62%. A total of 84 (9.7%) CV deaths were collected, with 39 (4.5%) occurring within 5 years. At multivariate analysis, both pHR% [hazard ratio 0.97 (0.95–0.99), P < 0.05] and pHRR% [hazard ratio 0.977 (0.961–0.993), P < 0.01] were associated with the primary endpoint. A pHR% ≤ 75% and a pHRR% ≤ 50% represented the most accurate cut-off values in predicting the outcome. Conclusion The study suggests an association between blunted exercise-HR response, functional capacity, and CV death risk among patients with HFmrEF. Whether the CI presence might be adopted in daily HFmrEF management needs to be addressed in larger prospective studies. Lay summary • Chronotropic incompetence is an easy-to-obtain additive parameter for cardiovascular death risk stratification in heart failure with mildly reduced ejection fraction (HFmrEF). • Peak heart rate and peak heart rate reserve are associated with exercise capacity in HFmrEF. • Peak heart rate and peak heart rate reserve are associated with cardiovascular death in HFmrEF

Prognostic Value of Indeterminable Anaerobic Threshold in Heart Failure.

Background In patients with heart failure (HF), during maximal cardiopulmonary exercise test, anaerobic threshold (AT) is not always identified. We evaluated whether this finding has a prognostic meaning. Methods and Results We recruited and prospectively followed up, in 14 dedicated HF units, 3058 patients with systolic (left ventricular ejection fraction <40%) HF in stable clinical conditions, New York Heart Association class I to III, who underwent clinical, laboratory, echocardiographic, and cardiopulmonary exercise test investigations at study enrollment. We excluded 921 patients who did not perform a maximal exercise, based on lack of achievement of anaerobic metabolism (peak respiratory quotient 1.05). Primary study end point was a composite of cardiovascular death and urgent cardiac transplant, and secondary end point was all-cause death. Median follow-up was 3.01 (1.39-4.98) years. AT was identified in 1935 out of 2137 patients (90.54%). At multivariable logistic analysis, failure in detecting AT resulted significantly in reduced peak oxygen uptake and higher metabolic exercise and cardiac and kidney index score value, a powerful prognostic composite HF index (P<0.001). At multivariable analysis, the following variables were significantly associated with primary study end point: peak oxygen uptake (% pred; P<0.001; hazard ratio [HR]=0.977; confidence interval [CI]=0.97-0.98), ventilatory efficiency slope (P=0.01; HR=1.02; CI=1.01-1.03), hemoglobin (P<0.05; HR=0.931; CI=0.87-1.00), left ventricular ejection fraction (P<0.001; HR=0.948; CI=0.94-0.96), renal function (modification of diet in renal disease; P<0.001; HR=0.990; CI=0.98-0.99), sodium (P<0.05; HR=0.967; CI=0.94-0.99), and AT nonidentification (P<0.05; HR=1.41; CI=1.06-1.89). Nonidentification of AT remained associated to prognosis also when compared with metabolic exercise and cardiac and kidney index score (P<0.01; HR=1.459; CI=1.09-1.10). Similar results were obtained for the secondary study end point. Conclusions The inability to identify AT most often occurs in patients with severe HF, and it has an independent prognostic role in HF

Soleus Muscle as a Surrogate for Health Status in Human Heart Failure

We propose the hypothesis that soleus muscle function may provide a surrogate measure of functional capacity in patients with heart failure. We summarize literature pertaining to skeletal muscle as a locus of fatigue and present our recent findings, using in vivo imaging in combination with biomechanical experimentation and modeling, to reveal novel structure-function relationships in chronic heart failure skeletal muscle and gait

Exercise intolerance in chronic heart failure : mechanisms and therapies. Part I

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 O-2 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. Eur J Cardiovasc Prev Rehabil 17:637-642 (C) 2010 The European Society of Cardiolog