Natalia Pezzali

Effect of Spironolactone on Left Ventricular Ejection Fraction and Volumes in Patients With Class I or II Heart Failure

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.

Cardiovascular and noncardiovascular comorbidities in patients with chronic heart failure

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.

Role of β1- and α2c-adrenergic receptor polymorphisms and their combination in heart failure: A case-control study☆

Adrenergic activation has a central role in the development of HF. The function of the β1‐ and the α2C‐adrenergic receptors is influenced by gene polymorphisms: the β1Arg389 variant is associated with increased β1‐receptor sensitivity and the α2C‐receptor Del322–325 variant is associated with decreased α2C receptor function and increased norepinephrine release. We hypothesised that these polymorphisms could influence the prevalence of heart failure.

Angiotensin-converting-enzyme gene polymorphism and heart failure: a case-control study.

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.

Effects of Spironolactone on Long-term Mortality and Morbidity in Patients With Heart Failure and Mild or No Symptoms

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.

Echocardiographic Evaluation of Asymptomatic Patients Affected by Rheumatoid Arthritis

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.

Elastic properties of the ascending aorta in patients with α1-antitrypsin deficiency (Z homozygotes)

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×cm2×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.

Quantitative Analysis of Right Ventricular (RV) Function With Echocardiography in Chronic Heart Failure With No or Mild RV Dysfunction Comparison With Cardiac Magnetic Resonance Imaging

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.

Adrenergic receptor gene polymorphism and left ventricular reverse remodelling after cardiac resynchronization therapy: preliminary results

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.

Elastic properties of the ascending aorta in patients with rheumatoid arthritis

Systemic inflammatory rheumatic diseases, such as rheumatoid arthritis (RA), are associatedwith increased cardiovascularmortality, on account of the high prevalence of ischemic heart disease and accelerated atherosclerosis, compared with ageand sex-matched controls [1]. The higher risk of cardiovascular disease (CVD) in RA patients seems to be independent of traditional cardiovascular risk factors. Different pathogenic mechanisms including pro-oxidative dyslipidemia, insulin resistance, prothrombotic state and hyperhomocysteinemia have been described [2]. However, immune activation is a key mechanism that promotes structural and functional abnormalities of the vascular bed. Arterial stiffness, usually measured by pulse-wave velocity analysis, is considered a marker of subclinical vascular disease and increased CVD risk, and it is markedly abnormal in patients with RA [3,4]. Large left ventricular (LV)masshas also been associatedwith RA, suggesting a link between chronic inflammation and LV hypertrophy [5].We investigated the elastic properties of the aorta and systo-diastolic function in RA patients without CV disease, compared with healthy controls. In our study, RA was diagnosed according to American College of Rheumatology criteria [6]. Disease activity was assessed at time of cardiological evaluation using a composite index, calledDAS44, including swollen and tender joint count (on 44 joints), global health assessment and ESR value. The patients had a cardiological examination, 12-lead electrocardiography (ECG) and two-dimensional and Doppler transthoracic echocardiography. The exclusion criteria of the study were: (a) arterial hypertension (blood pressure N140/90 mmHg in more than three consecutive readings or use of any hypotensive drugs); (b) diabetes; (c) smoke; (d) symptomatic dyspnea or chest pain; (e) use of any cardiovascular drugs (including statins); (g) any previous myocardial infarction, surgical or percutaneous revascularization, a positive ECG result, perfusion or echocardiographic exercise or pharmacological stress test; (h) more than mild aortic or mitral regurgitation and/or stenosis; (i) any previous surgical or interventional cardiac or vascular procedure; (l) familial hypercholesterolemia; (m) any genetic cardiovascular disease (including cardiomyopathy orMarfan syndrome). Patients were matched to normal controls for age, sex and ethnicity. The 44 selected RApatients have amean age of 55 years (±14 years) and mean duration of RA 9.6 years (±7.6 years). CRP was high at the time of the cardiac evaluation in 19 patients (43.2%). Rheumatoid factor and anti-cyclic citrullinatedpeptide (anti-CCP) antibodieswere found in 73.8% and 62% of subjects, respectively. Themean disease activity index, assessed using the DAS44 score, was low (mean 2.4±1.6). Prednisone, methotrexate, or anti-TNF agentswere currently being or had been used by respectively 95%, 80.5% and 63.4% of the patients. Table 1 shows their baseline demographic and cardiovascular data. Compared with ageand sex-matched controls, the RA patients had greater posterior wall and septal thickness, but no other differences from controls in terms of LV end-diastolic/end-systolic diameter or ejection fraction (Table 2). As a consequence, RA subjects had a greater LV mass (155±47 vs. 140±31 g; p=0.01), LV mass index (mean 140±31 vs. 92±25 g/m pb0.001) and indexing to height in meters to the power 2.7 (43±12 vs. 31±10 g/m ; p=0.0043) than controls. We also found lower mean aortic strain (7.7±3% vs. 13±5%; pb0.001) and distensibility (2.8±1.2 vs. 5.4±2.6 cm2dyn−1×10−6; pb0.001) with a highermean stiffness index (9.2±6.05 vs. 5.06±2.9; pb0.001) in RA cases, compared with controls. There was also a significant difference between RA patients and controls in term of E/A (1.1±0.7 vs. 1.7±0.6, pb0.001), deceleration time (225±56 vs. 190±50 ms, p=0.004) and E/E′ (10.3±5.5 vs. 7.3±3.5, pb0.01). A comparison of aortic distensibility and other morphological and functional cardiac parameters showed no significant association between LV mass with aortic distensibility, aortic strain and stiffness. In addition, RA duration, disease activity index (DAS 44) and CRP did not correlate with either LV mass or aortic elastic properties. Increased aortic stiffness and decreased aortic distensibility were closely associated with diastolic filling indexes measured by conventional and tissue Doppler echocardiography. In particular, we found a significant association between aortic distensibility, E/A (pb0.001) and E′ (p=0.013), aortic stiffness and deceleration time (p: 0.01) and between aortic strain, E/A (pb0.001) and E′ (p=0.02). After adjustment for age and systolic blood pressure, at multivariable stepwise regression analysis, RA (pb0.0001) and systolic blood pressure (p=0.022) were independently related with distensibility, only RA was independently related with stiffness (p=0.0003) and with strain (pb0.0001). Age (p=0.0004) and RA (p=0.0014) were independently related with E/A, while only RA (p=0.0069) was independently related with E/E′. RA (p=0.00154) and age (p=0.0076) were independently related with DT. At a multivariable stepwise regression analysis, rheumatoid factor, DAS, anti-CCP status were not related with aortic stiffness, distensibility, LV mass. Stratifying cases on the basis of RA duration (more or less than ten years), we also found no differences for LV mass and other elastic properties of the aortic wall. When considering RA treatment, prednisone, methotrexate or anti-TNF alpha therapies were not related with stiffness, distensibility, LV mass at multivariable regression analysis. The results of this study are that, first, patients with RAwithout CV disease or any CV risk factors had an increase in LVmass and abnormal elastic properties of the aorta (increased arterial stiffness, lower