Chiara Minà

Exercise tolerance can explain the obesity paradox in patients with systolic heart failure: Data from the MECKI Score Research Group

AIMS Obesity has been found to be protective in heart failure (HF), a finding leading to the concept of an obesity paradox. We hypothesized that a preserved cardiorespiratory fitness in obese HF patients may affect the relationship between survival and body mass index (BMI) and explain the obesity paradox in HF. METHODS AND RESULTS A total of 4623 systolic HF patients (LVEF 31.5 ± 9.5%, BMI 26.2 ± 3.6 kg/m(2) ) were recruited and prospectively followed in 24 Italian HF centres belonging to the MECKI Score Research Group. Besides full clinical examination, patients underwent maximal cardiopulmonary exercise test at study enrolment. Median follow-up was 1113 (553-1803) days. The study population was divided according to BMI (<25, 25-30, >30 to ≤35 kg/m(2) ) and predicted peak oxygen consumption (peak VO2 , <50%, 50-80%, >80%). Study endpoints were all-cause and cardiovascular deaths including urgent cardiac transplant. All-cause and cardiovascular deaths occurred in 951 (28.6%, 57.4 per person-years) and 802 cases (17.4%, 48.4 per 1000 person-years), respectively. In the high BMI groups, several prognostic parameters presented better values [LVEF, peak VO2 , ventilation/carbon dioxide slope, renal function, and haemoglobin (P < 0.01)] compared with the lower BMI groups. Both BMI and peak VO2 were significant positive predictors of longer survival: both higher BMI and peak VO2 groups showed lower mortality (P < 0.001). At multivariable analysis and using a matching procedure (age, gender, LVEF, and peak VO2 ), the protective role of BMI disappeared. CONCLUSION Exercise tolerance affects the relationship between BMI and survival. Cardiorespiratory fitness mitigates the obesity paradox observed in HF patients.

Deceptive meaning of oxygen uptake measured at the anaerobic threshold in patients with systolic heart failure and atrial fibrillation

Background Oxygen uptake at the anaerobic threshold (VO2AT), a submaximal exercise-derived variable, independent of patients’ motivation, is a marker of outcome in heart failure (HF). However, previous evidence of VO2AT values paradoxically higher in HF patients with permanent atrial fibrillation (AF) than in those with sinus rhythm (SR) raised uncertainties. Design We tested the prognostic role of VO2AT in a large cohort of systolic HF patients, focusing on possible differences between SR and AF. Methods Altogether 2976 HF patients (2578 with SR and 398 with AF) were prospectively followed. Besides a clinical examination, each patient underwent a maximal cardiopulmonary exercise test (CPET). Results The follow-up was analysed for up to 1500 days. Cardiovascular death or urgent cardiac transplantation occurred in 303 patients (250 (9.6%) patients with SR and 53 (13.3%) patients with AF, p = 0.023). In the entire population, multivariate analysis including peak oxygen uptake (VO2) showed a prognostic capacity (C-index) similar to that obtained including VO2AT (0.76 vs 0.72). Also, left ventricular ejection fraction, ventilation vs carbon dioxide production slope, β-blocker and digoxin therapy proved to be significant prognostic indexes. The receiver-operating characteristic (ROC) curves analysis showed that the best predictive VO2AT cut-off for the SR group was 11.7 ml/kg/min, while it was 12.8 ml/kg/min for the AF group. Conclusions VO2AT, a submaximal CPET-derived parameter, is reliable for long-term cardiovascular mortality prognostication in stable systolic HF. However, different VO2AT cut-off values between SR and AF HF patients should be adopted.

Renal Function and Peak Exercise Oxygen Consumption in Chronic Heart Failure With Reduced Left Ventricular Ejection Fraction

BACKGROUND Chronic kidney disease is associated with sympathetic activation and muscle abnormalities, which may contribute to decreased exercise capacity. We investigated the correlation of renal function with peak exercise oxygen consumption (V̇O2) in heart failure (HF) patients. METHODS AND RESULTS: We recruited 2,938 systolic HF patients who underwent clinical, laboratory, echocardiographic and cardiopulmonary exercise testing. The patients were stratified according to estimated glomerular filtration rate (eGFR). Mean follow-up was 3.7 years. The primary outcome was a composite of cardiovascular death and urgent heart transplantation at 3 years. On multivariable regression, eGFR was predictor of peakV̇O2(P<0.0001). Other predictors were age, sex, body mass index, HF etiology, NYHA class, atrial fibrillation, resting heart rate, B-type natriuretic peptide, hemoglobin, and treatment. After adjusting for significant covariates, the hazard ratio for primary outcome associated with peakV̇O2<12 ml·kg(-1)·min(-1)was 1.75 (95% confidence interval (CI): 1.06-2.91; P=0.0292) in patients with eGFR ≥60, 1.77 (0.87-3.61; P=0.1141) in those with eGFR of 45-59, and 2.72 (1.01-7.37; P=0.0489) in those with eGFR <45 ml·min(-1)·1.73 m(-2). The area under the receiver-operating characteristic curve for peakV̇O2<12 ml·kg(-1)·min(-1)was 0.63 (95% CI: 0.54-0.71), 0.67 (0.56-0.78), and 0.57 (0.47-0.69), respectively. Testing for interaction was not significant. CONCLUSIONS Renal dysfunction is correlated with peakV̇O2. A peakV̇O2cutoff of 12 ml·kg(-1)·min(-1)offers limited prognostic information in HF patients with more severely impaired renal function.

Multiparametric prognostic scores in chronic heart failure with reduced ejection fraction: a long-term comparison

Risk stratification in heart failure (HF) is crucial for clinical and therapeutic management. A multiparametric approach is the best method to stratify prognosis. In 2012, the Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score was proposed to assess the risk of cardiovascular mortality and urgent heart transplantation. The aim of the present study was to compare the prognostic accuracy of MECKI score to that of HF Survival Score (HFSS) and Seattle HF Model (SHFM) in a large, multicentre cohort of HF patients with reduced ejection fraction.

Heart failure and anemia: Effects on prognostic variables

BACKGROUND Anemia is frequent in heart failure (HF), and it is associated with higher mortality. The predictive power of established HF prognostic parameters in anemic HF patients is unknown. METHODS Clinical, laboratory, echocardiographic and cardiopulmonary-exercise-test (CPET) data were analyzed in 3913 HF patients grouped according to hemoglobin (Hb) values. 248 (6%), 857 (22%), 2160 (55%) and 648 (17%) patients had very low (<11g/dL), low (11-12 for females, 11-13 for males), normal (12-15 for females, 13-15 for males) and high (>15) Hb, respectively. RESULTS Median follow-up was 1363days (606-1883). CPETs were always performed safely. Hb was related to prognosis (Hazard ratio (HR)=0.864). No prognostic difference was observed between normal and high Hb groups. Peak oxygen consumption (VO2), ventilatory efficiency (VE/VCO2 slope), plasma sodium concentration, ejection fraction (LVEF), kidney function and Hb were independently related to prognosis in the entire population. Considering Hb groups separately, peakVO2 (very low Hb HR=0.549, low Hb HR=0.613, normal Hb HR=0.618, high Hb HR=0.542) and LVEF (very low Hb HR=0.49, low Hb HR=0.692, normal Hb HR=0.697, high Hb HR=0.694) maintained their prognostic roles. High VE/VCO2 slope was associated with poor prognosis only in patients with low and normal Hb. CONCLUSIONS Anemic HF patients have a worse prognosis, but CPET can be safely performed. PeakVO2 and LVEF, but not VE/VCO2 slope, maintain their prognostic power also in HF patients with Hb<11g/dL, suggesting CPET use and a multiparametric approach in HF patients with low Hb. However, the prognostic effect of an anemia-oriented follow-up is unknown.

Prognostic role of β-blocker selectivity and dosage regimens in heart failure patients. Insights from the MECKI score database

The use of β‐blockers represents a milestone in the treatment of heart failure with reduced ejection fraction (HFrEF). Few studies have compared β‐blockers in HFrEF, and there is little data on the effects of different doses. The present study aimed to investigate in a large database of HFrEF patients (MECKI score database) the association of β‐blocker treatment with a composite outcome of cardiovascular death, urgent heart transplantation or left ventricular assist device implantation, addressing the role of β‐selectivity and dosage regimens.

Multiparametric prognostic scores in chronic heart failure with reduced ejection fraction

Risk stratification in heart failure (HF) is crucial for clinical and therapeutic management. A multiparametric approach is the best method to stratify prognosis. In 2012, the Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score was proposed to assess the risk of cardiovascular mortality and urgent heart transplantation. The aim of the present study was to compare the prognostic accuracy of MECKI score to that of HF Survival Score (HFSS) and Seattle HF Model (SHFM) in a large, multicentre cohort of HF patients with reduced ejection fraction.

Diastolic dysfunction diagnosed by tissue Doppler imaging in cirrhotic patients: Prevalence and its possible relationship with clinical outcome☆

BACKGROUND Cirrhotic cardiomyopathy has been characterized by impaired contractile response to stress and/or altered diastolic relaxation, with electrophysiological abnormalities in the absence of known cardiac disease. However, the clinical significance of diastolic dysfunction (DDF) in cirrhotic patients has not been clarified. METHODS We studied 84 cirrhotic patients with normal systolic function to evaluate the prevalence of DDF using tissue Doppler imaging, and to investigate the possible correlation of DDF with outcomes (hospitalization, death) and with the specific causes of death. RESULTS The mean follow-up was 10±8months. DDF was diagnosed in 22 patients (26.2%). Patients with DDF more frequently had ascites (90.9% vs. 64.5 %; p=0.026), lower levels of albumin (OR: 5.39; p=0.004), higher NT-proBNP levels, and longer QTc interval (464±23ms vs. 452±30ms; p=0.039). At follow-up, patients with DDF did not have a higher incidence of adverse events in terms of hospitalization and death. CONCLUSIONS The presence of diastolic dysfunction has not been found to be clearly associated with outcome, and prognosis has been determined primarily by the severity of liver disease.

Biomechanical Determinants of Right Ventricular Failure in Pulmonary Hypertension

Pulmonary hypertension (PH) is a disease characterized by progressive adverse remodeling of the distal pulmonary arteries, resulting in elevated pulmonary vascular resistance and load pressure on the right ventricle (RV), ultimately leading to RV failure. Invasive hemodynamic testing is the gold standard for diagnosing PH and guiding patient therapy. We hypothesized that lumped-parameter and biventricular finite-element (FE) modeling may lead to noninvasive predictions of both PH-related hemodynamic and biomechanical parameters that induce PH. We created patient-specific biventricular FE models that characterize the biomechanical response of the heart and coupled them with a lumped-parameter model that represents the systemic and pulmonic circulation. Simulations were calibrated by adjusting the pulmonary vascular resistance and myocardial contractility parameters through matching imaging data of ventricular chambers. Linear regression analysis demonstrated that the lumped-derived RV cardiac index (CI) was in good agreement with catheterization measurements collected from 10 patients with PH (R2 = 0.82; p < 0.001). Biventricular FE analysis revealed a paradoxical leftward shift of the interventricular septum, and this correlated with invasive measurements of pulmonary vascular resistances (R = 0.70; p = 0.048) as found by Pearson’s coefficient. A significant difference was noted for RV myocardial fiber stress in healthy control patients (4.5 ± 0.7 kPa) compared with that of patients with PH at either rest (30.1 ± 12.1 kPa; p = 0.005) or simulated exercise conditions (69.6 ± 24.8 kPa; p < 0.001), thus suggesting adverse RV remodeling. This approach may become a useful and versatile tool for noninvasively assessing RV impairment induced by PH and realistically predicting ventricular mechanics and interactions for an improved management of patients with PH.

Risk Factors Associated With Peripheral Neuropathy in Heart Failure Patients Candidates for Transplantation

Introduction: Peripheral neuropathy can affect patients with heart failure, though its prevalence is unknown. After heart transplantation, it can influence the postoperative course and quality of life, but screening for neuromuscular disease is not routinely performed. Objective: The aim of this study was to identify the factors associated with neuropathy in a population of patients with heart failure who are candidates for heart transplantation. Study Design: Data regarding patients’ clinical history, including recent hospitalizations, were collected. All patients underwent a complete neurological examination and a neurophysiological protocol including nerve conduction studies and concentric needle electromyography. Results: Thirty-two patients were included in the study, and neuropathy was diagnosed in 10 (31.3%). Neuropathy was associated with the number of admissions (P = .023; odds ratio [OR]: 1.96) and the total number of days of hospitalization in the year prior to inclusion in the study (P = .010; OR: 1.03). The majority of hospitalizations occurred in the step-down unit (85%), with acute heart failure the leading cause of admission (42%). Conclusions: This study shows that neuropathy is frequent in patients with advanced heart failure and that hospitalization for cardiac care, also in the absence of intensive care, is a marker of high risk of neurologic damage. These data can help physicians in selecting and managing candidates for transplantation and can guide decisions on the best immunosuppressive regimen or rehabilitation strategy.