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Introduction: Tako-Tsubo cardiomyopathy (TTC) is an acute cardiomyopathy mimicking acute myocardial infarction. The aim of our study was to define clinical and instrumental features of an Italian population of patients with TTC and to report their short and mid-term outcome., Methods: We retrospectively evaluated 42 patients admitted to our Department with diagnosis of TTC (100% women, age 67 ± 11 years) using Mayo Clinic-modified criteria. In this population, we analyzed the stressful event (if present), the clinical presentation, the ECG and echocardiogram at admission and the markers of myocardial cytonecrosis, such as troponin I, at admission and during the hospitalization. All the patients have been clinically evaluated after 6 months and 1 year of follow-up., Results: In this population, a stressful event before TTC has been detected in 59% of patients. The most common clinical presentation was chest pain (81%) and the major sign was dyspnea (17%). ECG showed negative T waves and ST elevation, respectively, in 45 and 38%. Only 10% had a ST depression and 7% developed a newly acquired complete left bundle branch block. All of these abnormalities disappeared within 1.8 ± 0.9 days. The mean ejection fraction at admission was 35 ± 7% associated with apical (40%), mid-apical (56%) and mid-ventricular (4%) wall motion abnormalities. The recovery of these abnormalities occurred within 10 ± 3 days. At 6-month and 1-year follow-up, no patients had TTC recurrence, and 10 patients at 6 months and 20 patients at 1 year were re-hospitalized for a non-cardiac cause., Conclusion: Our data describe the characteristics of TTC in a small Italian population, which are similarly described in Japanese and North American people. TTC was related to a very low mortality, both in the short and mid term, but the risk of acute heart failure in the acute phase could not be neglected.

Objectives: Right ventricular (RV) performance parameters (tricuspid annular plane systolic excursion, systolic longitudinal velocity on tissue Doppler imaging, fractional area change, and tissue and 2-dimensional [2D] strain on the right free wall) have been validated. In comparative studies, they have been correlated with the prognosis of patients with heart failure on radionuclide ventriculography and thermodilution in right heart catheterization. This study aimed to evaluate RV systolic function in patients with heart failure with no or mild RV dysfunction and correlate the above-mentioned echocardiographic parameters with the magnetic resonance imaging (MRI)-calculated RV ejection fraction (RVEF), stroke volume, end-diastolic volume, and end-systolic volume., Methods: Standard and pulsed Doppler tissue echocardiography and MRI were performed in 31 patients with New York Heart Association functional class II and III chronic heart failure., Results: A high correlation between tricuspid annular plane systolic excursion, systolic longitudinal velocity, tissue strain, and 2D strain was noted, whereas the fractional area change did not correlate with any other parameter. The RVEF correlated with tricuspid annular plane systolic excursion, systolic longitudinal velocity, and tissue and 2D strain (all P< .01); under linear regression analysis, the 4 parameters independently correlated with RVEF., Conclusions: Echocardiographic RV performance parameters (tricuspid annular plane systolic excursion, systolic longitudinal velocity, tissue strain, and 2D strain) correlated with the MRI-calculated RVEF and overall predicted it. In particular, RV 2D strain and tissue strain were good markers for RV longitudinal motions. These echocardiographic parameters are easily obtained and may give important information about RV function for evaluation and prognostic stratification of patients with heart failure., (© 2015 by the American Institute of Ultrasound in Medicine.)

Background: : Aortic stiffness, an independent predictor of mortality and cardiovascular events, is common among patients affected by non-ischemic dilated cardiomyopathy (NIDC) and heart failure (HF)., Methods: : A total of 55 patients with diagnosis of NIDC (aged 60 ± 11 years, mean ejection fraction (EF) 35.2% ± 7.7%) admitted consecutively to our department for mild to moderate HF (NYHA class II-III) underwent an echocardiographic study and cardiopulmonary exercise test (CPX). We evaluated elastic properties of ascending aorta, i.e. aortic stiffness and aortic distensibility (mm Hg - 1 ), derived from ascending aorta systolic and diastolic diameter (mm/m 2 ) measured 3 cm above the valvular plane through 2D-guided M-mode echocardiography., Results: : Mean aortic stiffness was 15.63 ± 14.53 and aortic distensibility was 2.61 ± 2.39 mm Hg - 1 . Collected parameters at CPX were peak oxygen consumption (pVO 2 ) (ml/kg/min), anaerobic threshold (AT) and the slope of the relation between minute ventilation (VE) and carbon dioxide production (VCO 2 ). Mean pVO 2 was 15.4 ± 3.9 ml/kg/min, VE/VCO 2 ratio at AT was 36.1 ± 6.1. Functional capacity measured through peak VO 2 was found to be directly correlated with aortic distensibility (r = 0.47, p = - 0.0002) and negatively correlated to aortic stiffness index (r = - 0.51, p = - 0.0001). These results were the same at multivariate analysis, corrected by age, hypertension, diabetes mellitus and ejection fraction (respectively r = 0.27, p = 0.008 and r = - 1.75, p = 0.0002)., Conclusions: : HF patients due to NIDC elastic properties of ascending aorta, evaluated by echocardiography, are correlated with a reduced functional capacity.

Background: The purpose of this study is to evaluate long-term effects of spironolactone, an affordable and widely used aldosterone receptor blocker, in patients with heart failure (HF) and mild or no symptoms., Methods: The study is a single-blind, placebo-controlled, blinded endpoint, randomized study. Patients with New York Heart Association (NYHA) classes I to II HF and left ventricular ejection fraction < 40% were randomized to spironolactone or placebo in addition to optimal therapy. The primary endpoint was the composite of death from any cause or cardiovascular hospitalization., Results: A total of 130 patients were randomized to spironolactone (n = 65) or placebo (n = 65). Patients on spironolactone had a better event-free survival for cardiovascular death or cardiovascular hospitalizations and for cardiovascular hospitalizations alone. At multivariable analysis, only spironolactone therapy, left ventricular ejection fraction and serum creatinine levels had an independent prognostic value for the combined endpoint, whereas only spironolactone therapy and serum creatinine levels had an independent prognostic value for cardiovascular hospitalizations alone., Conclusions: Administration of spironolactone reduced the composite of death and cardiovascular hospitalization in patients with NYHA classes I to II HF. These results suggest that spironolactone could be beneficial when administered on top of optimal therapy among patients with HF and mild or no symptoms.

Aims: Several factors can influence the extent of left ventricular (LV) reverse remodelling after cardiac resynchronization therapy (CRT) in patients with heart failure (HF). Polymorphism in genes involved in cardiac remodelling, namely beta-adrenergic receptors (ARs), may have a role. We studied the influence of beta-1 Arg389Gly, beta-2 Arg16Gly, and beta-2 Gln27Glu ARs gene polymorphisms on the magnitude of reverse remodelling response to CRT and its possible correlations with the incidence of appropriate implantable cardioverter-defibrillator (ICD) shocks., Methods and Results: Beta-ARs were assessed in 101 patients with HF due to idiopathic (50.5%) or ischaemic (49.5%) dilated cardiomyopathy, undergoing CRT for standard indications [left ventricular ejection fraction (LVEF) 23.5 ± 7.5%, QRS ≥ 120 ms]. Left ventricular ejection fraction was measured by echocardiography at baseline, 6 months after CRT, and periodically afterwards. The LVEF change from baseline was of 3.1 ± 11 units among Gln27Gln, 8.3 ± 10.4 units among Gln27Glu, 11 ± 6.4 units among Glu27Glu carriers (P = 0.018 for Gln27Gln vs. Glu27Glu carriers), and 8.8 ± 9.8 units among Gln27Glu + Glu27Glu carriers (P = 0.006 vs. Gln27Gln). Gln27 homozygotes had a higher incidence of appropriate ICD shocks for fast ventricular tachycardia/ventricular fibrillation., Conclusion: Beta-2 Gln27Glu ARs gene polymorphism may influence LV reverse remodelling after CRT with Glu27Glu carriers showing the greatest improvement. It may also influence the incidence of malignant ventricular tachyarrhythmias.

Background: Rheumatoid arthritis (RA) is associated with increased mortality and morbidity because of accelerated atherosclerosis. The study assessed the prevalence of left and right ventricle diastolic and systolic dysfunction in outpatients with RA., Methods: The study included 93 outpatients with RA. In all patients and control group, echocardiographic conventional and tissue Doppler (TDI) studies were conducted., Results: In the group of RA patients, we found high prevalence of left ventricular systolic and diastolic dysfunction and right diastolic dysfunction compared with controls (13.5% vs 5.5 %, 76.3% vs 48.8% and 41.9% vs 6.6%, respectively; P < 0.001). Rheumatoid arthritis patients and controls showed significant differences about mitral, tricuspid, and pulmonary flow velocity curves; tissue Doppler curves of the lateral and the septal myocardial walls of the left ventricle; and basal myocardial free wall of the right ventricle. There were not any correlations between inflammatory and functional disease parameters and variables of systolic and diastolic function., Conclusions: Our study shows a high prevalence of left ventricular systolic and diastolic dysfunction in a population of outpatients affected by rheumatoid arthritis.

Objective and Design: α1-Antitrypsin deficiency (AATD) is a genetic disorder that may be a pathogenic factor in vascular aneurysms and dissection. The aim of this study was to measure the diameters of the Valsalva sinuses (VS), sinotubular junction (STJ), ascending aorta (AA) and aortic arch (AAr) and elastic properties of the AA (distensibility, stiffness and tissue Doppler imaging (TDI strain)) in AATD subjects., Patients: 33 AATD subjects (all Z-homozygous, 17 male, 16 female) were examined. Aortic elastic properties, namely, distensibility and stiffness index, were calculated from the echocardiographically-derived thoracic aortic diameters and TDI strain was measured on the wall of the AA 3 cm above the aortic valve. The results were compared with those obtained in healthy controls matched for age, sex and body mass index., Results: AATD subjects had larger aortic diameters (VS: 3.5 ± 0.5 vs 3.2 ± 0.5 cm, p<0.05; STJ 2.7 ± 0.4 vs 2.4 ± 0.4 cm, p<0.01; AA 3.3 ± 0.5 vs 2.9 ± 0.4 cm, p<0.01; AAr 2.3 ± 0.3 vs 2.1 ± 0.3 cm, p=0.05); greater aortic stiffness 14.9 ± 11.9 versus 7.4 ± 4.4 (pure numbers, p<0.005); and less aortic distensibility 2.4 ± 1.8 versus 4.0 ± 2.6 10(-6)×cm(2)×dyne(-1), p<0.005. Peak systolic (S) and diastolic (E and A) waves of the aortic wall TDI were similar in patients and controls (S wave: 5.4 ± 1.6 vs 5.9 ± 2.3 cm/s; E wave: -4.8 ± 2.2 vs -4.5 ± 2.2 cm/s; A wave: -6.1 ± 2.2 vs -6.2 ± 2.4 cm/s) while TDI strain of the aortic wall was lesser in patients than controls (-14.7 ± 8.0% vs -28.3 ± 7.1%, p<0.001)., Conclusions: AATD subjects have a larger AA with abnormal elastic properties as compared to controls. The increase in stiffness, decrease in distensibility and abnormal strain of the aortic wall may all reflect pathological changes in its elastic tissue.

Background: Plasma levels of tumor marker carbohydrate 125 antigen (CA 125) have been found elevated among patients with advanced heart failure (HF). We evaluated the prognostic value of CA125 in a population of patients with mild to moderate HF., Methods and Results: Serum levels of CA 125 were obtained in 102 patients with mild to moderate HF from idiopathic (48%) or ischemic (52%) dilated cardiomyopathy (age 64 ± 10.4 years, left ventricular ejection fraction: 34.4 ± 8.5%), under optimized medical therapy. During follow-up (43 ± 15 months), 16 (15.7%) cardiovascular deaths and 23 (22.5%) cardiovascular deaths + HF hospitalizations were recorded. Considering cardiac death, comparison of Kaplan-Meier survival curves by the log-rank test showed that patients with CA 125 levels higher than the cut-off value (30 U/mL) had a worse survival (P < .0001). This was observed also when considering cardiovascular death+ HF hospitalizations as the secondary end point (P = .0003). Event-free survival was assessed by Kaplan-Meier method and log-rank test. Multivariable Cox proportional stepwise hazards regression analysis was performed and showed that CA 125 and systolic pulmonary artery pressure (sPAP) were significantly associated with the risk of cardiovascular deaths + HF hospitalizations (HR 1.01, 95% CI 1.02-1.06, and HR 1.07, 95% CI 1.02-1.1, P < .001, respectively)., Conclusions: In mild-to-moderate HF patients under optimized therapy, higher plasma CA 125 levels are an effective long-term prognostic marker in forecasting cardiovascular events and HF hospitalization and may contribute to a better risk stratification., (Copyright © 2012 Elsevier Inc. All rights reserved.)

A broad spectrum of concomitant disorders may complicate heart failure adding further morbidity and mortality risk. Comorbidities may be subdivided into cardiovascular and noncardiovascular. The first group includes hypertension, coronary artery disease, peripheral artery disease, cerebrovascular disease, arrhythmias and valvular heart disease. Noncardiovascular comorbidities include respiratory, endocrine, metabolic, nutritional, renal, hematopoietic, neurological as well as musculoskeletal conditions. In recent years, advances in the treatment of heart failure have not been attended by important changes in management of its comorbidities. They now seem to be major causes of the poor prognosis of heart failure patients. In this review we provide an updated summary of the epidemiological, pathophysiological and clinical characteristics of comorbidities as well as their potential impact for heart failure treatment., (2011 Italian Federation of Cardiology.)

The beneficial effects of spironolactone in chronic heart failure (HF) have been demonstrated in patients with New York Heart Association (NYHA) class III to IV HF. This study examined the effect of spironolactone on left ventricular (LV) function and functional capacity of patients with mild to moderate HF (NYHA class I to II). One hundred sixty-eight patients with NYHA class I to II HF and LV ejection fraction ≤40% were randomized to spironolactone or placebo and assessed by echocardiography, gated single-photon emission computed tomography, technetium-99m sestamibi single-photon emission computed tomographic radionuclide ventriculography, and cardiopulmonary exercise testing at baseline and after 6 months of treatment. In the spironolactone group LV ejection fraction increased from 35.2 ± 0.7% to 39.1 ± 3.5% (p <0.001), with a decrease in LV end-diastolic and end-systolic volumes and myocardial mass and an improvement in LV diastolic filling pattern. Cardiopulmonary exercise testing parameters did not change. In conclusion, administration of spironolactone to patients with NYHA class I to II HF has beneficial effects on LV remodeling and diastolic function., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: Beta-blockers are mainstay of current treatment of heart failure (HF). Beta-adrenergic receptors (AR) single nucleotide gene polymorphisms (SNPs) may influence the sensitivity and density of beta-AR. We assessed the relation between three common beta-AR SNPs and the response to carvedilol administration., Methods and Results: We studied 183 consecutive patients with chronic HF due to ischemic or nonischemic cardiomyopathy, a LV ejection fraction (LVEF) < or = 0.35, not previously treated with beta-blockers. Each patient underwent gated-SPECT radionuclide ventriculography, cardiopulmonary exercise testing and invasive hemodynamic monitoring at baseline and after 12 months of carvedilol administration at maintenance dosages. The beta1-AR gene Arg389Gly and the beta2-AR gene Arg16Gly SNPs were not related to the response to carvedilol administration. Homozygotes for the Glu27Glu allele showed a greater increase in the LVEF, compared to the other patients (+13.0 +/- 12.2% versus +7.1 +/- 8.1% in the Gln27Gln homozygotes, and 8.3 +/- 11.4% units in the Gln27Glu heterozygotes; p = 0.022 by ANOVA). Glu27Glu homozygotes also showed a greater decline in the pulmonary wedge pressure both at rest and at peak exercise. Gln27Glu SNP was selected amongst the determinants of the LVEF response to carvedilol at multivariable analysis, in addition to the cause of cardiomyopathy, baseline systolic blood pressure and the dose of carvedilol administered., Conclusion: Beta1-AR Arg389Gly and beta2-AR Arg16Gly SNPs are not related to the response to carvedilol therapy. In contrast, the Gln27Glu SNP is a determinant of the LVEF response to this agent in patients with chronic HF.

Diastolic heart failure (DHF) currently accounts for more than 50% of all heart failure patients. DHF is also referred to as heart failure with normal left ventricular (LV) ejection fraction (HFNEF) to indicate that HFNEF could be a precursor of heart failure with reduced LVEF. Because of improved cardiac imaging and because of widespread clinical use of plasma levels of natriuretic peptides, diagnostic criteria for HFNEF needed to be updated. The diagnosis of HFNEF requires the following conditions to be satisfied: (i) signs or symptoms of heart failure; (ii) normal or mildly abnormal systolic LV function; (iii) evidence of diastolic LV dysfunction. Normal or mildly abnormal systolic LV function implies both an LVEF > 50% and an LV end-diastolic volume index (LVEDVI) <97 mL/m(2). Diagnostic evidence of diastolic LV dysfunction can be obtained invasively (LV end-diastolic pressure >16 mmHg or mean pulmonary capillary wedge pressure >12 mmHg) or non-invasively by tissue Doppler (TD) (E/E' > 15). If TD yields an E/E' ratio suggestive of diastolic LV dysfunction (15 > E/E' > 8), additional non-invasive investigations are required for diagnostic evidence of diastolic LV dysfunction. These can consist of blood flow Doppler of mitral valve or pulmonary veins, echo measures of LV mass index or left atrial volume index, electrocardiographic evidence of atrial fibrillation, or plasma levels of natriuretic peptides. If plasma levels of natriuretic peptides are elevated, diagnostic evidence of diastolic LV dysfunction also requires additional non-invasive investigations such as TD, blood flow Doppler of mitral valve or pulmonary veins, echo measures of LV mass index or left atrial volume index, or electrocardiographic evidence of atrial fibrillation. A similar strategy with focus on a high negative predictive value of successive investigations is proposed for the exclusion of HFNEF in patients with breathlessness and no signs of congestion. The updated strategies for the diagnosis and exclusion of HFNEF are useful not only for individual patient management but also for patient recruitment in future clinical trials exploring therapies for HFNEF.

Background: Adrenergic activation has a central role in the development of HF. The function of the beta1- and the alpha2C-adrenergic receptors is influenced by gene polymorphisms: the beta1Arg389 variant is associated with increased beta1-receptor sensitivity and the alpha2C-receptor Del322-325 variant is associated with decreased alpha2C receptor function and increased norepinephrine release. We hypothesised that these polymorphisms could influence the prevalence of heart failure., Methods: The role of the beta1- and alpha2C-adrenergic receptor gene polymorphisms as risk factors for heart failure (HF) was assessed in an Italian white Caucasian population using a case-control study design. Genomic DNA was analysed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RLFP)., Results: We compared 260 Caucasian patients with HF and 230 normal subjects. The beta1Arg389 allele was frequent both in the patients with HF (69%) and in the normal subjects (73%). The alpha2CDel322-325 variant was rare in both groups (9% and 8%, respectively). Patients homozygotes for either the beta1Arg389 or the alpha(2C)Del322-325 alleles had no increased risk of HF (odds ratio [OR], 0.8; 95%CI: 0.5-1.2 and OR, 0.8; 95% CI: 0.4-1.8, respectively). Patients homozygotes for both the beta1Arg389 and the alpha(2C)Del322-325 alleles had no increased risk of HF as well (OR: 0.6; 95% CI: 0.2-2.1)., Conclusions: Beta1-ARs and alpha2C-ARs polymorphisms are not associated with an increased risk of HF in an Italian white Caucasian population.

Background: We hypothesised that the polymorphisms of the genes encoding for beta1- and the beta2-adrenoceptors may have a role in the pathogenesis of heart failure (HF). We therefore compared the polymorphisms of the beta1-adrenoceptor gene (Arg389Gly), the beta2-adrenoceptor gene (Arg16Gly, Gln27Glu) and their combinations in patients with HF and normal subjects living in the same area., Methods and Results: A total of 256 cases with HF (left ventricular ejection fraction < or = 40%) and 230 normal subjects were enrolled. The beta1- and beta2-adrenoceptor gene polymorphisms were assessed by PCR, followed by restriction enzyme digestion. No differences were observed in the distribution of any of the three genotypes studied in patients with HF and normal subjects. An analysis of the genotype combinations showed a non-significant increase in the risk of HF associated with the Arg389Gly16Gln27 (odds ratio = 1.4; 95%CI 0.5-3.6) and Arg389Gly16 Glu27 (odds ratio = 1.2; 95%CI, 0.5-2.8) homozygous allele combinations., Conclusion: None of the three most common polymorphisms of beta-adrenoreceptors are associated with an increased risk of HF., (Copyright 2004 Elsevier Ltd)

Heart failure (HF) is the final outcome of virtually all cardiovascular diseases and is a major and increasingly serious public health problem. The renin-angiotensin system plays an important role in the pathogenesis of cardiovascular disease. Insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) has attracted significant attention; it has been extensively investigated in a spectrum of cardiovascular phenotypes because of its correlation with serum ACE activity. There is controversy regarding the association of ACE I/D polymorphism with cardiovascular disease. The aim of this study was to investigate whether ACE genotype is associated with HF by comparing cases and controls. The study sample consisted of 229 cases with HF due to coronary heart disease or idiopathic dilated cardiomyopathy and 230 controls recruited from the general population. The ACE I/D genotype was identified using a polymerase chain reaction assay. No evidence was found to support an association between ACE genotype and HF.