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.

[The role of myocardial scintigraphy in the assessment of coronary artery disease]. / Il ruolo della scintigrafia miocardica nella valutazione della cardiopatia ischemica.

Single photon emission computed tomography (SPECT) for the assessment of myocardial perfusion was introduced in the early 1970s, following pioneer studies of Gould et al. It has rapidly become one of the most used noninvasive technique for the assessment of myocardial ischemia. Thanks to the current technetium based tracers that allow electrocardiogram gated synchronization, it is possible to assess the regional ventricular systolic function and the evaluation of myocardial perfusion as well. In the last twenty years, beyond its diagnostic role, myocardial SPECT has become also a prognostic technique. Indeed, it has acquired a role for the short-term prediction of major coronary events in a large cohort with known or suspected coronary artery disease (CAD). The aim of this review is to give an update of the correct use and interpretation of myocardial SPECT in patients with known or suspected CAD and without left ventricular dysfunction.

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.

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. Egger's 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.

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.

Prevalence and severity of asymptomatic coronary and carotid artery disease in patients with lower limbs arterial disease.

OBJECTIVES: Lower limbs arterial disease (LLAD) portends high risk of cardiovascular events. Yet, the prevalence of significant occult coronary artery (CAD) and cerebrovascular (CVD) disease in patients without CAD and CVD has not been widely investigated. The purpose of this study was to evaluate the prevalence and severity of CAD and CVD in patients with LLAD of the lower extremities. METHODS: From January 2008 through December 2011 we studied 200 consecutive patients admitted for symptomatic LLAD, with normal global and regional systolic function, no symptoms of angina or dyspnea. During hospital admission all patients underwent carotid Doppler study and invasive angiography. RESULTS: Significant CAD was observed in 110 of 200 (55%) patients. Fifty-eight (53%) patients with significant CAD showed either left main (n = 7), 3 vessels (n = 35) or proximal left anterior descending (n = 16) CAD, corresponding to 29% of total cohort. CVD was detected in 86(43%) patients (69% with concomitant CAD), including 30(35%) with severe and 15(17%) with significant disease. In thirty-two (37%) patients with CVD either left main (n = 4), 3 vessels (n = 18) or proximal left anterior descending (n = 10) CAD was observed. The percent of patients with left main, 3 vessel or proximal left anterior descending stenosis among those with CVD was significantly higher (37%; p = 0.03) compared to those without CVD. CONCLUSIONS: Severe asymptomatic CAD and CVD are quite prevalent in LLAD, and 29% of patients fulfill indications for coronary revascularization. Cost-effective strategies to detect occult CAD or CVD in LLAD patients need to be investigated in large multicenter studies.

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.

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]. / Applicazioni cliniche della SPECT con MIBG nello scompenso cardiaco cronico.

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.

Cardiovascular effects of antiretroviral drugs: clinical review.

In HIV infected patients an increased occurence of cardiac events has been demontrated from the introduction of highly active antiretroviral therapy (HAART). Antiretroviral drugs' regimens are, in fact, associated with several metabolic side effects, such as dyslipidemia, impaired glucose metabolism and abnormal body fat distribution, that increase the cardiovascular risk of HIV subjects. In addition, HIV infection itself, the chronic inflammatory status and the relevant presence in this population of some of the traditional cardiovascular risk factors contribute to an higher incidence of cardio and cerebrovascular events. In last years several studies showed the occurence of carotid vascular impairment in patients in treatment with protease inhibitors (PI). Similarly the DAD Study reported an increase of 26% of the risk of myocardial infarction in patients on HAART and that this risk is indipendently associated with longer exposure to PI, even after multivariate adjustments. A correct evaluation of the metabolic status before starting HAART and an adeguate control of the drugs-related metabolic abnormalities may reduce the incidence of cardiac events and still improve HIV patients prognosis. This review will focus on the metbolic effects of antiretroviral drugs and to the contribution of combination antiretroviral therapy on cardiovascular risk.