Teresa Losco

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.

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.

Effects of Dipeptidyl Peptidase 4 Inhibitors and Sodium-Glucose Linked coTransporter-2 Inhibitors on cardiovascular events in patients with type 2 diabetes mellitus: A meta-analysis

BACKGROUND Dipeptidyl Peptidase 4 Inhibitors (DPP4-I) and Sodium-Glucose Linked coTransporter-2 Inhibitors (SGLT2-I) improve glycemic control in patients with type 2 diabetes mellitus (DM). However, only few studies were designed to assess the efficacy and safety of these drugs on cardiovascular (CV) events and mortality. The purpose of the current study was to evaluate the effects of DPP4-Is and SGLT2-Is on CV events and mortality by meta-analysis. METHODS Randomized trials enrolling more than 200 patients, comparing DPP-4-Is or SGLT2-Is versus placebo or active treatments in patients with DM, and reporting at least one event among all-cause and CV mortality, stroke, myocardial infarction (MI) and new onset of heart failure (HF), were included. RESULTS 157 randomized trials (114 on DPP4-Is and 43 on SGLT2-Is) enrolling 140,470 patients (107,100 in DPP4-I and 33,370 in SGLT2-I studies) were included in the analysis. Compared to control, treatment with DPP4-Is did not affect all-cause (RR: 1.010; 95% CI: 0.935-1.091) and CV (RR: 0.975; CI: 0.887-1.073) mortality as well as risk of MI (RR: 0.915; CI: 0.835-1.002), stroke (RR: 0.933; CI: 0.820-1.062) and HF (RR: 1.083; CI: 0.973-1.205). Treatment with SGLT2-Is significantly reduced the risk of all-cause death by 28% (RR: 0.718; CI: 0.613-0.840), CV death by 33% (RR: 0.668; CI: 0.544-0.821), MI by 20% (RR: 0.803; CI: 0.668-0.965) and HF by 35% (RR: 0.652; CI: 0.517-0.823) without effect on stroke (RR: 1.158; CI: 0.912-1.469). CONCLUSIONS DPP4-Is show a safe CV profile as they do not affect mortality and CV events, including HF, in patients with type 2 DM. SGLT2-Is are associated with improved CV outcome and survival in DM patients.

Implantable cardioverter defibrillator to prevent sudden cardiac death in a patient with systemic sclerosis: A clinical case

Ventricular arrhythmias are frequent in patients with systemic sclerosis and may result in sudden cardiac death. We report the case of a patient with systemic sclerosis and recent syncopes in whom induction of unstable sustained ventricular tachycardia of 2 different morphologies accompanied by syncopal event was demonstrated at the electrophysiological study. He was then implanted a 3rd generation implantable cardioverter defibrillator and remained thereafter asymptomatic. We suggest that aggressive testing is warranted in systemic sclerosis patients with suspected malignant arrhythmias to identify candidates for defibrillator implantation and prevent sudden deaths.

Clinical applications of MIBG SPECT in chronic heart failure

Heart failure is characterized by several abnormalities of sympathetic cardiac activity that can be assessed by 123I metaiodobenzylguanidine single photon emission computed tomography (MIBG SPECT). This technique may be useful in the clinical management of heart failure patients. Abnormal MIBG uptake has been demonstrated to be a predictor of death and arrhythmic events in heart failure patients with a prognostic power incremental to that of conventional risk markers; it may also be useful to identify patients at low risk of arrhythmias despite current guideline indications for an implantable cardioverter-defibrillator (ICD) or patients at high risk for arrhythmias not fulfilling ICD indications. This review will focus on the clinical applications of MIBG SPECT in chronic heart failure, on the basis of the most recent evidence.

DO CHANGES OF BRAIN NATRIURETIC AND N-TERMINAL PRO-B-TYPE NATRIURETIC PEPTIDES PREDICT CARDIOVASCULAR EVENTS IN HEART FAILURE PATIENTS? A META-ANALYSIS OF 27 TRIALS IN 15,820 PATIENTS

The relationship between brain natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) plasma levels and risk of cardiovascular events in patients with heart failure (HF) has been demonstrated in previous studies. However, it is unclear whether changes of BNP and NT-

Role of Angiotensin-Receptor Blockers in the Prevention of Cardiovascular Risk: Clinical Guidelines

The development and progression of cardiovascular disease can be regarded as a continuum (Fig. 1) [1]. Targeting different points within this continuum is therefore of major importance for reducing cardiovascular morbidity and mortality. Inhibition of the renin-angiotensin-aldosterone system (RAAS) has become a key target in this regard, given that angiotensin II (Ang II) has been implicated as a pathogenic factor at many steps in the development and progression of cardiovascular disease [2, 3].