Prevalence and prognostic impact of non-cardiac co-morbidities in heart failure outpatients with preserved and reduced ejection fraction: a community-based study.

AIM: To assess adverse outcomes attributable to non-cardiac co-morbidities and to compare their effects by left ventricular ejection fraction (LVEF) group [LVEF <50% (heart failure with reduced ejection fraction, HFrEF), LVEF ≥50% (heart failure with preserved ejection fraction, HFpEF)] in a contemporary, unselected chronic heart failure population. METHODS AND RESULTS: This community-based cohort enrolled patients from October 2009 to December 2013. Adjusted hazard ratio (HR) and the population attributable fraction (PAF) were used to compare the contribution of 15 non-cardiac co-morbidities to adverse outcome. Overall, 2314 patients (mean age 77 ±10 years, 57% men) were recruited [n = 941 (41%) HFrEF, n = 1373 (59%) HFpEF]. Non-cardiac co-morbidity rates were similarly high, except for obesity and hypertension which were more prevalent in HFpEF. At a median follow-up of 31 (interquartile range 16-41) months, 472 (20%) patients died. Adjusted mortality rates were not significantly different between the HFrEF and HFpEF groups. After adjustment, an increasing number of non-cardiac co-morbidities was associated with a higher risk for all-cause mortality [HR 1.25; 95% confidence interval (CI) 1.10-1.26; P < 0.001], all-cause hospitalization (HR 1.17; 95% CI 1.12-1.23; P < 0.001), heart failure hospitalization (HR 1.28; 95% CI 1.19-1.38; P < 0.001), non-cardiovascular hospitalization (HR 1.16; 95% CI 1.11-1.22; P < 0.001). The co-morbidities contributing to high PAF were: anaemia, chronic kidney disease, chronic obstructive pulmonary disease, diabetes mellitus, and peripheral artery disease. These findings were similar for HFrEF and HFpEF. Interaction analysis yielded similar results. CONCLUSIONS: In a contemporary community population with chronic heart failure, non-cardiac co-morbidities confer a similar contribution to outcomes in HFrEF and HFpEF. These observations suggest that quality improvement initiatives aimed at optimizing co-morbidities may be similarly effective in HFrEF and HFpEF.

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

AIMS: 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. METHODS AND RESULTS: We collected data on 6112 HF patients and compared the prognostic accuracy of MECKI score, HFSS, and SHFM at 2- and 4-year follow-up for the combined endpoint of cardiovascular death, urgent cardiac transplantation, or ventricular assist device implantation. Patients were followed up for a median of 3.67 years, and 931 cardiovascular deaths, 160 urgent heart transplantations, and 12 ventricular assist device implantations were recorded. At 2-year follow-up, the prognostic accuracy of MECKI score was significantly superior [area under the curve (AUC) 0.781] to that of SHFM (AUC 0.739) and HFSS (AUC 0.723), and this relationship was also confirmed at 4 years (AUC 0.764, 0.725, and 0.720, respectively). CONCLUSION: In this cohort, the prognostic accuracy of the MECKI score was superior to that of HFSS and SHFM at 2- and 4-year follow-up in HF patients in stable clinical condition. The MECKI score may be useful to improve resource allocation and patient outcome, but prospective evaluation is needed.

Systolic blood pressure target in systemic arterial hypertension: Is lower ever better? Results from a community-based Caucasian cohort.

BACKGROUND: Extensive evidence exists about the prognostic role of systolic blood pressure (SBP) reduction ≤140mmHg. Recently, the SPRINT trial successfully tested the strategy of lowering SBP<120mmHg in patients with arterial hypertension (AH). AIM: To assess whether the SPRINT results are reproducible in a real world community population. METHODS: Cross-sectional, population-based study analyzing data of 24,537 Caucasian people with AH from the Trieste Observatory of CV disease, 2010 to 2015. We selected and divided 2306 subjects with AH according to the SPRINT trial criteria; similarly, SPRINT clinical outcomes were considered. RESULTS: Study patients median age was 75±8years, two third male, one third had ischemic heart disease. They were older, with lower body mass index, higher SBP and Framingham CV risk score than the SPRINT patients. Three-hundred-sixty-eight patients (16%) had SBP<120mmHg. During 48 [36-60] months of follow-up, 751 patients (32%) experienced a major adverse cardiac event (MACE). The SBP <120mmHg group had higher incidence of MACE, CV deaths and all-cause death than SBP≥120mmHg group (37% vs 31%; 10% vs 4%; 19% vs 10%, all p<0.05). The condition of SBP<120mmHg was an independent predictor of MACE in multivariate Cox analysis together with older age, male gender, higher Charlson score. CONCLUSIONS: In our experience, the SBP<120mmHg condition is associated with worse clinical outcomes, suggesting the SPRINT results are not reproducible tout court in Caucasian community populations. These differences should be taken as a warning against aggressive reducing of SBP<120mmHg.

Left ventricular function and exercise performance in idiopathic dilated cardiomyopathy: role of tissue Doppler imaging.

BACKGROUND: To examine the relationship between left ventricular (LV) function evaluated at echocardiography and exercise performance in idiopathic dilated cardiomyopathy (IDCM) patients. METHODS AND RESULTS: We enrolled 76 consecutive IDCM patients in sinus rhythm, undergoing cardiopulmonary exercise testing and echocardiography [49 ±â€Š13 years old; LV ejection fraction 31 ±â€Š7%, LV end-diastolic volume 96 ±â€Š31 ml/m; peak oxygen consumption (peak VO2/kg) 18 ±â€Š5.6 ml/kg/min]. Linear regression analysis revealed that peak systolic velocity (S') (r = 0.46; P < 0.001) and E/E' (r = -0.43; P < 0.001), two tissue Doppler imaging derived parameters, were related to peak VO2/kg, whereas ejection fraction and mitral inflow variables were not. Considering the 69 patients (90%) without diastolic restrictive pattern (a well known index of severe diastolic dysfunction), multivariate regression analysis showed that age, E/E' and S' were the only independent variables related to peak VO2/kg. Similarly, age and E/E' were confirmed as independent parameters for the prediction of ventilation/carbon dioxide production slope in the whole population. CONCLUSION: In IDCM patients, cardiopulmonary exercise performance variables were strongly related to E/E' and S'.

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

AIMS: The use of ß-blockers represents a milestone in the treatment of heart failure with reduced ejection fraction (HFrEF). Few studies have compared ß-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 ß-blocker treatment with a composite outcome of cardiovascular death, urgent heart transplantation or left ventricular assist device implantation, addressing the role of ß-selectivity and dosage regimens. METHODS AND RESULTS: In 5242 HFrEF patients, we investigated the role of: (i) ß-blocker treatment vs. non-ß-blocker treatment, (ii) ß1-/ß2-receptor-blockers vs. ß1-selective blockers, and (iii) daily ß-blocker dose. Patients were followed for 3.58 years, and 1101 events (18.3%) were observed; 4435 patients (86.8%) were on ß-blockers, while 807 (13.2%) were not. At 5 years, ß-blocker-patients showed a better outcome than non-ß-blocker-subjects [hazard ratio (HR) 0.48, P < 0.0001], while also considering potential confounders. A comparable prognosis was observed at 5 years in the ß1-/ß2-receptor-blocker (n = 2219) vs. ß1-selective group (n = 2216) (HR 0.95, P = ns). A better prognosis was observed in high-dose (>2 5 mg carvedilol equivalent daily dose, n = 1005) patients than in both medium dose (12.5-25 mg, n = 1431) and low dose (<12.5 mg, n = 1960) (HR 1.97, P < 0.001; HR 1.95, P = 0.001, respectively), with no differences between the last two groups (HR 0.84, P = ns). CONCLUSION: In a large population of chronic HFrEF patients, ß-blockers were associated with a more favourable prognosis without any difference between ß1- and ß2-receptor-blockers vs. ß1-selective blockers. A better outcome was observed in subjects receiving a high daily dose.

Prognostic value of cardiopulmonary exercise testing in Idiopathic Dilated Cardiomyopathy.

BACKGROUND: Although cardiopulmonary exercise testing (CPET) is considered as an important tool in risk stratification of patients with heart failure (HF), prognostic data in the specific setting of Idiopathic Dilated Cardiomyopathy (iDCM) are still undetermined. The aim of the study was to test the prognostic value of CPET in a large cohort of iDCM patients. METHODS AND RESULTS: We analyzed 381 iDCM patients who consecutively performed CPET. The study end-point was a composite of cardiovascular death/urgent heart transplantation (CVD/HTx). In the overall population the average values of peak oxygen consumption (peak VO2/kg) and percent-predicted peak VO2 (peak VO2%) were 17.1±5.1ml/kg/min and 59±15%, respectively. Mean VE/VCO2 slope was 29.8±6.1. During a median follow-up of 47months (interquartile range 23-84), 83 patients experienced CVD/HTx. Peak VO2% (Area Under the Curve [AUC] 0.74; 95% CI 0.71-0.85, p<0.001) and VE/VCO2 slope (AUC 0.78; 95% CI 0.74-0.84, p<0.001) were more accurate in predicting CVD/HTx compared to peak VO2/kg (AUC 0.60; 95% CI 0.54-0.68, p=0.003) (p<0.001 for both comparisons). The most accurate threshold values for outcome prediction in our iDCM cohort were <60% for peak VO2% and >29 for VE/VCO2 slope. At multivariable analysis peak VO2% and VE/VCO2 slope were the strongest predictors of CVD/HTx, either as continuous and categorical variables, whereas peak VO2/kg was not independently related with prognosis. CONCLUSION: In a large population of iDCM patients peak VO2% and VE/VCO2 slope emerged as the strongest prognostic CPET variables. Prospective studies will be necessary to confirm these data.

Clinical management of dilated cardiomyopathy: current knowledge and future perspectives.

Dilated cardiomyopathy (DCM) is a primary heart muscle disease characterized by a progressive dilation and dysfunction of either the left or both ventricles. The management of DCM is currently challenging for clinicians. The persistent lack of knowledge about the etiology and pathophysiology of this disease continues to determine important fields of uncertainty in managing this condition. Molecular cardiology and genetics currently represent the most crucial horizon of increasing knowledge. Understanding the mechanisms underlying the disease allows clinicians to treat this disease more effectively and to further improve outcomes of DCM patients through advancements in etiologic characterization, prognostic stratification and individualized therapy. Left ventricular reverse remodeling predicts a lower rate of major cardiac adverse events independently from other factors. Optimized medical treatment and device implantation are pivotal in inducing left ventricular reverse remodeling. Newly identified targets, such as angiotensin-neprilysin inhibition, phosphodiesterase inhibition and calcium sensitizing are important in improving prognosis in patients affected by DCM.