Francesca Musella

Do changes of 6-minute walk distance predict clinical events in patients with pulmonary arterial hypertension? A meta-analysis of 22 randomized trials.

OBJECTIVES The objectives of this study were to verify whether improvement in 6-min walk distance (6MWD) is associated with clinical outcome in pulmonary arterial hypertension (PAH). BACKGROUND 6MWD is used as an endpoint to assess the benefit of therapies in PAH. However, whether changes in 6MWD correlate with clinical outcome is unknown. METHODS Randomized trials assessing 6MWD in patients with PAH and reporting clinical endpoints were included in a meta-analysis. The meta-analysis was performed to assess the influence of treatment on outcomes. Meta-regression analysis was performed to test the relationship between 6MWD changes and outcomes. RESULTS Twenty-two trials enrolling 3,112 participants were included. Active treatments led to significant reduction of all-cause death (odds ratio [OR]: 0.429; 95% confidence interval [CI]: 0.277 to 0.664; p < 0.01), hospitalization for PAH, and/or lung or heart-lung transplantation (OR: 0.442; 95% CI: 0.309 to 0.632; p < 0.01), initiation of PAH rescue therapy (OR: 0.555; 95% CI: 0.347 to 0.889; p = 0.01), and composite outcome (OR: 0.400; 95% CI: 0.313 to 0.510; p < 0.01). No relationship between 6MWD changes and outcomes was detected. CONCLUSIONS In patients with PAH, improvement in 6MWD does not reflect benefit in clinical outcomes.

Benefits of statins in elderly subjects without established cardiovascular disease: a meta-analysis.

OBJECTIVES The purpose of this paper was to assess whether statins reduce all-cause mortality and cardiovascular (CV) events in elderly people without established CV disease. BACKGROUND Because of population aging, prevention of CV disease in the elderly is relevant. In elderly patients with previous CV events, the use of statins is recommended by guidelines, whereas the benefits of these drugs in elderly subjects without previous CV events are still debated. METHODS Randomized trials comparing statins versus placebo and reporting all-cause and CV mortality, myocardial infarction (MI), stroke, and new cancer onset in elderly subjects (age ≥ 65 years) without established CV disease were included. RESULTS Eight trials enrolling 24,674 subjects (42.7% females; mean age 73.0 ± 2.9 years; mean follow up 3.5 ± 1.5 years) were included in analyses. Statins, compared with placebo, significantly reduced the risk of MI by 39.4% (relative risk [RR]: 0.606 [95% confidence interval (CI): 0.434 to 0.847]; p = 0.003) and the risk of stroke by 23.8% (RR: 0.762 [95% CI: 0.626 to 0.926]; p = 0.006). In contrast, the risk of all-cause death (RR: 0.941 [95% CI: 0.856 to 1.035]; p = 0.210) and of CV death (RR: 0.907 [95% CI: 0.686 to 1.199]; p = 0.493) were not significantly reduced. New cancer onset did not differ between statin- and placebo-treated subjects (RR: 0.989 [95% CI: 0.851 to 1.151]; p = 0.890). CONCLUSIONS In elderly subjects at high CV risk without established CV disease, statins significantly reduce the incidence of MI and stroke, but do not significantly prolong survival in the short-term.

Changes of Natriuretic Peptides Predict Hospital Admissions in Patients With Chronic Heart Failure: A Meta-Analysis

OBJECTIVES The goal of this study was to explore the association between changes in B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) plasma levels and risk of hospital admission for heart failure (HF) worsening in patients with chronic HF. BACKGROUND The relationship between BNP and NT-proBNP plasma levels and risk of cardiovascular events in patients with chronic HF has been previously demonstrated. However, it is unclear whether changes in BNP and NT-proBNP levels predict morbidity in patients with chronic HF. METHODS The MEDLINE, Cochrane, ISI Web of Science, and SCOPUS databases were searched for papers about HF treatment up to August 2013. Randomized trials enrolling patients with systolic HF, assessing BNP and/or NT-proBNP at baseline and at end of follow-up, and reporting hospital stay for HF were included in the analysis. Meta-regression analysis was performed to test the relationship between BNP and NT-proBNP changes and the clinical endpoint. Sensitivity analysis was performed to assess the influence of baseline variables on results. Eggers linear regression was used to assess publication bias. RESULTS Nineteen trials enrolling 12,891 participants were included. The median follow-up was 9.5 months (interquartile range: 6 to 18 months), and 22% of patients were women. Active treatments significantly reduced the risk of hospital stay for HF worsening. In meta-regression analysis, changes in BNP and NT-proBNP were significantly associated with risk of hospital stay for HF worsening. Results were confirmed by using sensitivity analysis. No publication bias was detected. CONCLUSIONS In patients with HF, reduction of BNP or NT-proBNP levels was associated with reduced risk of hospital stay for HF worsening.

Takotsubo Cardiomyopathy: Overview

Takotsubo cardiomyopathy (TTC) is a unique acute syndrome characterized by transient left ventricular systolic dysfunction in the absence of significant coronary artery disease, occurring mostly in postmenopausal women after emotional and/or physical stress. Given the nonspecific symptoms and signs, a high clinical index of suspicion is necessary to detect the disease in different clinical settings and scenarios. Noninvasive multimodality imaging may be useful to distinguish this cardiomyopathy from other acute cardiac and thoracic diseases. Coronary angiography remains, however, mandatory to differentiate TTC from acute coronary syndromes. This article reviews the clinical features and management of TTC and some new insights.

Effects of atorvastatin and rosuvastatin on renal function: A meta-analysis

BACKGROUND Atorvastatin (A) and rosuvastatin (R) are highly effective and widely used statins. However, conflicting results have been reported regarding their renal effects. The aim of the present study was to compare the effects of A and R on glomerular filtration rate (GFR) and new onset proteinuria in patients at high cardiovascular risk. METHODS Randomized trials about A or R treatments reporting clinical end-points were included in the meta-analysis. Influence of both treatments on GFR and new onset proteinuria was assessed. RESULTS 23 trials enrolling 29,147 participants were included. A significant reduction in GFR was detected in placebo-treated compared to statin-treated patients (standard mean difference [SMD]: 0.056, 95% confidence interval [CI]:0.028 to 0.083, p<0.01). In particular, a significant reduction in GFR was detected in placebo as compared to either R-treated (SMD: 0.052, CI: 0.022 to 0.081, p=0.001) or A-treated patients (SMD: 0.084, CI: 0.008 to 0.161, p=0.031). No significant difference in GFR was detected in 5 head-to-head studies comparing A to R (SMD: 0.043, CI: -0.041 to 0.126, p=0.319). In 9 studies comparing A to R, R treatment significantly increased the risk of proteinuria when compared to A (odds ratio [OR]: 0.656, CI: 0.440 to 0.977, p=0.038, heterogeneity p=0.026), but this effect was no longer significant when studies using highest therapeutic doses of R (40 mg/daily) were excluded from analysis, abolishing significant heterogeneity (OR: 1.505, CI: 0.827 to 2.739, p=0.181). CONCLUSIONS A and R show similar reno-protective effects in patients at high cardiovascular risk, with comparable rates of new onset proteinuria when commonly used doses are considered.

Haemodynamics, exercise capacity and clinical events in pulmonary arterial hypertension

The purpose of this study was to clarify whether changes in cardiopulmonary haemodynamics induced by pharmacological therapy correlate with exercise capacity and clinical events in patients with pulmonary arterial hypertension. 16 randomised trials including 2353 patients, followed up for 16.4±10.6 weeks, measuring cardiopulmonary haemodynamics by right heart catheterisation and reporting clinical events were included. Meta-analysis and meta-regression analysis were performed to assess the effects of treatments on clinical events and the relationship between haemodynamic changes (pulmonary artery pressure, pulmonary vascular resistance, cardiac index and right atrial pressure) and clinical events. Treatments significantly reduced all-cause death (OR 0.5, 95% CI 0.3–0.7; p<0.01), hospitalisation for pulmonary arterial hypertension (OR 0.4, 95% CI 0.2–0.7; p<0.01), initiation of rescue therapy (OR 0.3, 95% CI 0.2–0.6; p<0.01) and the composite outcome (OR 0.3, 95% CI 0.3–0.5; p<0.01). No relationship was found between changes of haemodynamic parameters and clinical events, whereas changes of cardiac index and pulmonary vascular resistance significantly correlated with changes in the 6-min walking distance (r = 0.64, p = 0.03; r = -0.55, p = 0.04, respectively). In patients with pulmonary arterial hypertension, improvements of cardiopulmonary haemodynamics observed in randomised clinical trials correlate with exercise capacity changes but do not predict clinical events in a short-term follow-up.

Assessment of cardiac sympathetic activity by MIBG imaging in patients with heart failure: a clinical appraisal

Cardiac sympathetic activity can be assessed by 123I-labelled meta-iodobenzylguanidine (MIBG) scintigraphy. Abnormalities of sympathetic cardiac activity have been shown in patients with heart failure, resulting in reduced MIBG uptake. Abnormal MIBG uptake predicts cardiac death, arrhythmias and all-cause mortality in patients with heart failure with a prognostic power incremental to that of conventional risk markers, and may identify patients at low risk of arrhythmias despite current guideline indications for implantable cardioverter defibrillator or patients at high risk for arrhythmias not fulfilling implantable cardioverter defibrillator indications. Prospective outcome studies are needed to assess whether MIBG imaging will have an impact on the mortality and morbidity of patients with heart failure.

Reduction of albumin urinary excretion is associated with reduced cardiovascular events in hypertensive and/or diabetic patients. A meta-regression analysis of 32 randomized trials

BACKGROUND The association between renal dysfunction and risk of cardiovascular (CV) events and mortality has been reported in several studies. However, it is unclear whether reduction in urinary albumin excretion (UAE) is associated with reduced risk of clinical events. Therefore, we sought to investigate, in a meta-regression analysis of randomized studies enrolling hypertensive and/or diabetic patients, whether changes in UAE are associated with changes in CV outcomes and all-cause mortality. METHODS MEDLINE, ISI Web of Science, Cochrane Database and Scopus were searched for randomized trials enrolling more than 200 diabetic and/or hypertensive patients, reporting UAE at baseline and at end of follow-up and CV events [CV death, myocardial infarction (MI), and stroke], as well all-cause mortality. RESULTS Thirty-two trials enrolling 80,812 participants were included in analyses. Meta-regression analysis showed that each 10% reduction of UAE was significantly associated with 13% reduction of MI (Regression Coefficient [RC]:0.0055; 95% Confidence Interval [CI]:0.0014 to 0.0095; p=0.010), with 29% reduction of stroke (RC:0.0124; CI:0.0030 to 0.0218; p=0.013) and with 14% reduction of the composite outcome (CV death, MI, stroke)(RC:0.0059; CI:0.0027 to 0.0090; p=0.001), whereas not significantly associated with all-cause (RC:0.0028; CI:-0.0047 to 0.0103; p=0.486) and CV mortality (RC:0.0028; CI:-0.0047 to 0.0103; p=0.447). Results were mostly confirmed by sensitivity analysis. No heterogeneity or publication bias was detected. CONCLUSIONS Reduction in UAE is associated with reduced risk of MI and stroke in diabetic and/or hypertensive patients. These findings suggest that UAE changes may represent a valuable intermediate end-point for CV risk evaluation in clinical practice.

Effects of ranolazine in symptomatic patients with stable coronary artery disease. A systematic review and meta-analysis.

BACKGROUND Ranolazine (R), as add-on therapy in symptomatic patients with chronic stable coronary artery disease (CAD), has been tested in randomized clinical studies. Aim of the study was to assess in a meta-analysis the effects of R on angina, nitroglycerin consumption, functional capacity, electrocardiographic signs of ischemia and hemodynamic parameters in patients with chronic CAD. METHODS Randomized trials assessing the effects of R compared to control on exercise duration, time to onset of angina, time to 1mm ST-segment depression, weekly nitroglycerin consumption and weekly angina frequency were included in the analysis. The effects of R compared to control on heart rate and blood pressure were also analyzed. RESULTS Six trials enrolling 9223 patients were included in the analysis. At trough and peak levels, R compared to control significantly improved exercise duration, time to onset of angina and time to 1mm ST-segment depression. Additionally, R compared to control significantly reduced weekly angina frequency and weekly nitroglycerin consumption. Finally, R compared to control did not significantly reduce supine systolic and diastolic blood pressure as well as heart rate, standing heart rate and diastolic blood pressure, whereas it modestly reduced standing systolic blood pressure. At sensitivity analysis, results were not influenced by concomitant background therapy. CONCLUSIONS In symptomatic patients with chronic CAD, R, added to conventional therapy, effectively reduces angina frequency and sublingual nitroglycerin consumption while prolonging exercise duration as well as time to onset of ischemia and to onset of angina with no substantial effects on blood pressure and heart rate.

Coronary computed tomography: current role and future perspectives for cardiovascular risk stratification

Coronary artery disease (CAD) is the major cause of morbidity and mortality worldwide. More than 50% of CAD deaths occur in previously asymptomatic individuals at intermediate cardiovascular risk, highlighting the need of more accurate individual risk assessment to decrease cardiovascular events. Cardiac computed tomography (CCT) has emerged as a valuable technique for risk stratification in asymptomatic subjects and in symptomatic patients without known CAD. The absence of coronary artery calcium (CAC) identifies asymptomatic subjects at very low cardiac risk and is reasonable in intermediate risk individuals, in whom CAC measurement reclassifies a substantial number of subjects to different risk categories. In symptomatic patients with suspected CAD, detection of non-obstructive or obstructive CAD by CCT angiography is associated with increased all-cause mortality, and provides incremental risk stratification to CAC. Further studies are needed to assess the impact of CCT on clinical outcomes and its cost-effectiveness in different clinical settings.