Cosimo Carriere

New-onset left bundle branch block independently predicts long-term mortality in patients with idiopathic dilated cardiomyopathy: data from the Trieste Heart Muscle Disease Registry.

AIMS Left bundle branch block (LBBB) is commonly associated with heart failure. We evaluated the prevalence, incidence, and impact of LBBB on long-term outcome in young patients with heart failure affected by idiopathic dilated cardiomyopathy (DCM). METHODS AND RESULTS We included 608 patients with DCM from the Heart Muscle Disease Registry of Trieste in this retrospective analysis. At baseline electrocardiogram (ECG), 189 patients (31.1%) had LBBB. The patients with baseline LBBB had a significantly higher mortality rate than the patients without LBBB (38.6 vs. 27.9%, P = 0.002) at the univariate analysis. After a multiple covariate adjustment, the baseline LBBB was not associated with a significantly increased risk of death [hazard ratio (HR) 1.27, 95% confidence interval (CI): 0.88-1.81, P = 0.2]. Forty-seven (11.2%) patients without LBBB at baseline ECG developed LBBB during follow-up. Among these, the mortality rate was 49 vs. 25% in patients without new-onset LBBB (P = 0.001). New-onset LBBB was a strong and independent predictor of all-cause mortality (HR 3.18, 95% CI: 1.90-5.31, P < 0.001) at multivariate analysis. CONCLUSION After correcting for potential confounders, new-onset LBBB was found to be associated with an increased risk of all-cause mortality. The management of patients with new-onset LBBB may need to be more aggressive, possibly including early cardiac resynchronization therapy/implantable cardioverter-defibrillator therapy.

Obesity and high waist circumference are associated with low circulating pentraxin-3 in acute coronary syndrome

BackgroundLong pentraxin 3 (PTX3) is a component of the pentraxin superfamily and a potential marker of vascular damage and inflammation, associated with negative outcome in patients with acute coronary syndromes (ACS). Obesity is a risk factor for cardiovascular disease and PTX3 production is reported in abdominal adipose tissue. Low PTX3 is however reported in the obese population, and obesity per se may be associated with less negative ACS outcome.MethodsWe investigated the potential impact of obesity and high waist circumference (reflecting abdominal fat accumulation) on plasma PTX3 concentration in ACS patients (n = 72, 20 obese) compared to age-, sex- and BMI-matched non-ACS individuals.ResultsBoth obese and non-obese ACS patients had higher PTX3 than matched non-ACS counterparts, but PTX3 was lower in obese than non-obese individuals in both groups (all P < 0.05). PTX3 was also lower in ACS subjects with high than in those with normal waist circumference (WC). Plasma PTX3 was accordingly associated negatively with BMI and WC, independently of age and plasma creatinine. No associations were observed between PTX3 and plasma insulin, glucose or the short pentraxin and validated inflammation marker C-reactive protein, that was higher in ACS than in non-ACS individuals independently of BMI or WC.ConclusionsObesity is associated with low circulating PTX3 in ACS. This association is also observed in the presence of abdominal fat accumulation as reflected by elevated waist circumference. Low PTX3 is a novel potential modulator of tissue damage and outcome in obese ACS patients.

Vitamin D Deficiency in Patients with Acute Myocardial Infarction: An Italian Single-Center Study

BACKGROUND Hypovitaminosis D is a vitamin deficiency that has been increasing in developed countries; it was also suggested as an emerging risk factor for developing of atherosclerosis and acute myocardial infarction. The primary source of vitamin D is its cutaneous synthesis under exposure to sunlight. It has been suggested that 30 min of sun exposure twice weekly leads to sufficient vitamin D synthesis. The residents of Trieste (Italy) are well-known for their high exposure to sunlight in all seasons. We aimed to investigate the vitamin D status in subjects with acute myocardial infarction living in this area. METHODS Vitamin D status was identified in 478 subjects diagnosed with acute myocardial infarction. RESULTS The median serum 25-hydroxyvitamin D concentration was 14.5 [7.8 - 22.7] ng/mL. Vitamin D deficiency and insufficiency were present in 324 (68 %) and 107 (22 %) subjects, respectively. Vitamin D deficiency was less frequent among subjects enrolled in the period from July to the end of September (p < 0.001). In a multivariate analysis vitamin D deficiency was predicted by older age (p = 0.02), female gender (p = 0.002), higher body mass index (p = 0.05), autumn/winter sampling (p < 0.001), increased parathyroid hormone (p = 0.03) and alkaline phosphatase (p = 0.003). CONCLUSIONS We observed very high prevalence of vitamin D deficiency among subjects with myocardial infarction in all seasons of enrollment. However, it was lower in the summer when sun exposure is higher. The exposure to sunlight may be a cost-saving therapeutic strategy for the management of vitamin D deficiency.

Interleukin-1β levels predict long-term mortality and need for heart transplantation in ambulatory patients affected by idiopathic dilated cardiomyopathy

Aims The prognostic stratification of patients with Idiopathic Dilated Cardiomyopathy (iDCM) is a difficult task. Here, we assessed the additive value of the evaluation of biomarkers of inflammasome activation and systemic inflammation for the long-term risk stratification of iDCM patients. Methods and Results We studied 156 ambulatory iDCM patients (mean age 58 years, 77% men, 79% in NYHA class 1-2, median Left Ventricular Ejection Fraction (LVEF) 35%, mean sodium 139 mEq/L, median BNP 189 pg/mL, median IL-1 beta (IL-1β) 1.08 pg/mL, median IL-6 1.7 pg/mL and median IL-10 2.7 pg/mL). During the follow-up period of 89.6 months, 35 patients (22%) died/underwent heart transplantation. Patients who died/underwent heart transplantation were more likely to be male, to be in NYHA class III, to have atrial fibrillation, to have lower LVEF and higher BNP levels. IL-1β, IL-6 and IL-10 levels did not differ significantly between the groups of patients with good or bad prognosis. IL-1β levels did not vary significantly among either the different NYHA classes or the quartiles of LVEF. In a multivariable model, however, IL-1β was a strong and independent predictor of all-cause mortality (HR 1.193, 95% CI 1.056 – 1.349, p=0.005 for log squared transformed values). Other factors associated with the outcome were: male gender, presence of atrial fibrillation and sodium concentration. The estimated time-dependent ROC curve of the multivariable model showed an AUC 0.74 (95% CI 0.65-0.86). Conclusions Serum levels of IL-1β could be useful to predict the long-term outcome of patients with iDCM.

U-shaped relationship between vitamin D levels and long-term outcome in large cohort of survivors of acute myocardial infarction

BACKGROUND Previous studies in the setting of patients with acute myocardial infarction (AMI) have demonstrated that hypovitaminosis D is associated with increased mortality risk during a follow-up whose median did not exceed two years. OBJECTIVE To evaluate the impact of vitamin D levels on long-term mortality in patients with AMI. RESULTS In our study 477 patients with AMI were included. During a median follow-up period of 57 (IQR 53-64) months, 93 patients (20%) died. A non-linear U-shaped relationship between 25(OH)D levels and long-term mortality was observed; patients with vitamin D<10ng/mL and >30ng/mL had higher mortality rate than those with intermediate values. After adjustment for differences in baseline features and treatment, it was confirmed that extreme values of vitamin D (<10 or >30ng/mL) are independent predictors of mortality with HR of 3.02 (95% CI 1.78-5.11). Other independent predictors of outcome were age, NYHA class at discharge, treatment with ACE inhibitors and statins. The estimated time-dependent ROC curve of the multivariable model including vitamin D showed an AUC significantly higher than the model without vitamin D: AUC 0.82 (95% CI 0.76-0.87) vs. 0.77 (95% CI 0.71-0.83), p=0.005. Addition of vitamin D to the model that included all significant factors for mortality improved the prognostic accuracy as showed by the metrics of reclassification (NRI 0.34 (95% CI 0.14-0.48), p=0.003 and IDI 0.06 (95% CI 0.01-0.12, p=0.005 p=0.03). CONCLUSIONS We report a U-shaped relationship between vitamin D levels and long-term outcome of patients surviving AMI.

Adipokines, Ghrelin and Obesity‐Associated Insulin Resistance in Nondiabetic Patients with Acute Coronary Syndrome

Altered glucose metabolism negatively modulates outcome in acute coronary syndromes (ACS). Insulin resistance is commonly associated with increasing BMI in the general population and these associations may involve obesity‐related changes in circulating ghrelin and adipokines. We aimed at investigating interactions between BMI, insulin resistance and ACS and their associations with plasma ghrelin and adipokine concentrations. Homeostasis model assessment of insulin resistance (HOMAIR)‐insulin resistance index, plasma adiponectin, leptin, total (T‐Ghrelin), acylated (Acyl‐Ghrelin), and desacylated ghrelin (Desacyl‐Ghrelin) were measured in 60 nondiabetic ACS patients and 44 subjects without ACS matched for age, sex, and BMI. Compared with non‐ACS, ACS patients had similar HOMAIR and plasma adipokines, but lower T‐ and Desacyl‐Ghrelin and higher Acyl‐Ghrelin. Obesity (BMI > 30) was associated with higher HOMAIR, lower adiponectin, and higher leptin (P < 0.05) similarly in ACS and non‐ACS subjects. In ACS (n = 60) HOMAIR remained associated negatively with adiponectin and positively with leptin independently of BMI and c‐reactive protein (CRP) (P < 0.05). On the other hand, low T‐ and Desacyl‐Ghrelin with high Acyl‐Ghrelin characterized both obese and non‐obese ACS patients and were not associated with HOMAIR. In conclusion, in ACS patients, obesity and obesity‐related changes in plasma leptin and adiponectin are associated with and likely contribute to negatively modulate insulin resistance. ACS per se does not however enhance the negative impact of obesity on insulin sensitivity. High acylated and low desacylated ghrelin characterize ACS patients independently of obesity, but are not associated with insulin sensitivity.

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.

Predictive role of CHA2DS2-VASc score for cardiovascular events and death in patients with arterial hypertension and stable sinus rhythm

Background The CHA2DS2-VASc score well stratifies the risk for thromboembolic events in non-valvular atrial fibrillation (NVAF) patients. This score may also predict thromboembolic events in sinus rhythm populations. Purpose The purpose of this study was to assess the prognostic role of CHA2DS2-VASc in a Caucasian community population of patients with arterial hypertension and sinus rhythm. Methods A total of 12,599 arterial hypertension residents not receiving anticoagulation were selected from a community population in Trieste between November 2009 and October 2014: 11,159 sinus rhythm and 1440 NVAF patients. We considered thromboembolic events, cardiovascular hospitalisation and all-cause death in all patients divided according to CHA2DS2-VASc. Results Sinus rhythm patients were 74 (interquartile range 65–81) years old, 50% were women, 32% with CAD, mean CHA2DS2-VASc 3.68 ± 1.47 points, significantly lower than NVAF patients (4.26 ± 1.50, P < 0.001). After 37 months follow-up, an increasing CHA2DS2-VASc corresponded to a higher rate of thromboembolic events in sinus rhythm patients, ranging from 0% in patients with a score of 1 or 2 to 2.6% in those with a score of 6 or greater (P < 0.0001). A similar trend was found in the reference NVAF group. At Cox multivariable analysis, CHA2DS2-VASc predicted thromboembolic events (hazard ratio (HR) 2.12), cardiovascular hospitalisation (HR 1.55) and all-cause death (HR 1.57). The predictive accuracy of CHA2DS2-VASc was similar in sinus rhythm and NVAF patients for thromboembolic events, cardiovascular hospitalisation and all-cause death (area under the curve statistic 0.76 vs. 0.76, 0.68 vs. 0.66, 0.64 vs. 0.64, respectively). Conclusions In a community population of Caucasian arterial hypertension patients in sinus rhythm, CHA2DS2-VASc rather well stratifies for adverse clinical events at mid-term follow-up with a similar accuracy to NVAF patients. These results might be clinically relevant in this setting of sinus rhythm patients.

Mineralocorticoid receptor antagonists for heart failure: a real-life observational study: Mineralocorticoid receptor antagonists in HF

Mineralocorticoid receptor antagonists (MRAs) have been demonstrated to improve outcomes in reduced ejection fraction heart failure (HFrEF) patients. However, MRAs added to conventional treatment may lead to worsening of renal function and hyperkalaemia. We investigated, in a population‐based analysis, the long‐term effects of MRA treatment in HFrEF patients.

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 ± 13 years old; LV ejection fraction 31 ± 7%, LV end-diastolic volume 96 ± 31 ml/m2; peak oxygen consumption (peak VO2/kg) 18 ± 5.6 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′.