MicroRNAs: diagnostic, prognostic and therapeutic role in heart failure-a review.

Heart failure is a leading cause of morbidity and mortality, with relevant social and economic burden on global healthcare system. Although the development of novel diagnostic tools and the advance in therapies have deeply influenced the diagnosis and treatment of this disease, improving both prognosis and life expectancy of patients, hospitalization is still high, and mortality remains considerable. MicroRNAs are small endogenous RNA molecules that post-transcriptionally regulate gene expression in both physiological and pathological processes. In recent years, microRNA have arisen as attractive therapeutic targets in the treatment of a wide spectrum of pathologies, including heart failure. In cardiac pathology, deregulation of microRNAs expression and function is associated to adverse outcome and heart failure progression. Circulating levels of specific microRNAs have emerged as useful biomarkers for the diagnosis of heart failure or as prognostic indicators. In the present review, we summarize the state of current research on the role of miRNAs as biomarkers for diagnosis and prognosis in patients with heart failure and their use as potential therapeutic targets for this condition.

Renal function and cardiac adrenergic impairment in patients affected by heart failure.

Although in heart failure (HF) there is a strict correlation between heart and kidney, no data are available on the potential relationship in HF between renal dysfunction (RD) and the impaired sympathetic innervation. Aim of the present study was to assess the relationship between RD and cardiac sympathetic innervation in HF patients with reduced ejection fraction. Two hundred and sixty-three patients with mild-to-severe HF underwent iodine-123 meta-iodobenzylguanidine myocardial scintigraphy to assess sympathetic innervation, evaluating early and late heart-to-mediastinum (H/M) ratios and washout rate. In all patients, glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula was assessed. A direct association was found between EPI-eGFR and late H/M (r = .215; P < .001). Dividing the population into moderate-to-severe eGFR reduction and normal-to-mildly reduced eGFR (cutoff ≤ 60 mL·min-1·1.73 m-2), a statistically significant reduction of late H/M value was found in patients with RD compared to patients with preserved eGFR (P = .030). By multivariable linear regression analysis, eGFR resulted in the prediction of impaired late H/M in patients with RD (P = .005). Patients with RD and HF show more impaired cardiac sympathetic activity than HF patients with preserved renal function, and reduced eGFR is a predictor of reduced late H/M.

Effects of glucagon-like peptide-1 receptor agonists on major cardiovascular events in patients with Type 2 diabetes mellitus with or without established cardiovascular disease: a meta-analysis of randomized controlled trials.

AIMS: Glucose-lowering, glucagon-like peptide-1 (GLP-1) receptor agonists reduce incidence of major cardiovascular (CV) events in patients with Type 2 diabetes mellitus (DM). However, randomized clinical trials reported inconsistent effects on myocardial infarction (MI) and stroke, and limited data in DM patients without established CV disease (CVD). Very recently, new relevant evidence was available from additional CV outcome trials (CVOTs) that also included large subgroups of patients with DM without established CVD. Thus, the aim of this meta-analysis was to investigate the effects of GLP-1 receptor agonists on major CV events and safety in DM patients with and without established CVD. METHODS AND RESULTS: In this trial-level meta-analysis, we analysed data from randomized placebo-controlled CVOTs assessing efficacy and safety of GLP-1 receptor agonists in adult patients with Type 2 DM. We searched PubMed, Embase, Cochrane, ISI Web of Science, SCOPUS, and clinicaltrial.gov databases for eligible trials. Of 360 articles identified and screened for eligibility, seven CVOTs were included, with an overall of 56 004 patients included. The difference in efficacy with respect to the major adverse cardiovascular events (MACE) primary endpoint (including CV mortality, non-fatal MI, and non-fatal stroke) between patients with established CVD and patients with CV risk factors only was not significant [pooled interaction effect, expressed as ratio of hazard ratio (HR) 1.06, 95% confidence interval (CI) 0.85-1.34]. In the analysis of the whole population of DM patients, GLP-1 receptor agonists showed a significant 12% reduction in the hazard of the three-point MACE composite endpoint (HR 0.88, 95% CI 0.80-0.96) and a significant reduction in the risk of CV mortality (HR 0.88, 95% CI 0.79-0.98), all-cause mortality (HR 0.89, 95% CI 0.81-0.97), fatal and non-fatal stroke (HR 0.84, 95% CI 0.76-0.94), and heart failure (HF) hospitalization (HR 0.92, 95% CI 0.86-0.97). No significant effect was observed for fatal and non-fatal MI (HR 0.91, 95% CI 0.82-1.02), although in a sensitivity analysis, based on a less conservative statistical approach, the pooled HR become statistically significant (HR 0.91, 95% CI 0.83-1.00; P = 0.039). No excess of hypoglycaemia, pancreatitis, and pancreatic cancer was observed between GLP-1 receptor agonists and placebo. CONCLUSION: Glucagon-like peptide-1 receptor agonists significantly reduce MACE, CV and total mortality stroke, and hospitalization for HF, with a trend for reduction of MI, in patients with Type 2 DM with and without established CVD.

The metabolic syndrome in heart failure: insights to specific mechanisms.

The presence of comorbidities significantly influences long-term morbidity and mortality of symptomatic and asymptomatic heart failure (HF) patients. Metabolic syndrome and diabetic cardiomyopathy are two clinical conditions that share multiple pathophysiological mechanisms and that might be both responsible for cardiac dysfunction. However, it is argued whether metabolic syndrome (MS) independently increases HF risk or the association between MS and HF merely reflects the impact of individual risk factors included in its definition on HF development. Similarly, in the context of diabetic cardiomyopathy, many aspects are still challenging starting from the definition up to the therapeutic management. In this clinical review, we focused the attention on molecular pathways, myocyte alterations, and specific patterns of metabolic syndrome and diabetic cardiomyopathy in order to better define the potential diagnostic and therapeutic approaches of these two pathological conditions.

Left Ventricular Function, Epicardial Adipose Tissue, and Carotid Intima-Media Thickness in Children and Adolescents With Vertical HIV Infection.

BACKGROUND: Life expectancy of HIV patients has increased considerably as a result of antiretroviral therapy (ART), and cardiovascular (CV) disease has emerged as an important late concern. People with HIV infection could have an impaired systolic function; however data on diastolic function and markers of CV risk, such as epicardial adipose tissue (EAT) and intima-media thickness (IMT), are lacking. Aim of this study is to evaluate left ventricular function, EAT, and IMT in children and adolescents with vertically acquired HIV infection. METHODS: We enrolled 29 subjects on ART (13, 45% men; median age of 13.0, and interquartile range 9-18), and 29 age-matched controls. All patients and controls underwent echocardiographic evaluation, with study of the systolic and diastolic function and measurement of the EAT, and a carotid ultrasound study for IMT measurement. RESULTS: Comparing HIV-infected patients to healthy controls, we found a statistically significant increase of EAT and IMT (mean ± SD) (EAT: 3.16 ± 1.05 vs 1.24 ± 0.61 mm; P < 0.0001. IMT: 0.77 ± 0.15 vs 0.51 ± 0.11 mm; P < 0.0001), and a significant reduction of ejection fraction, evaluated with the biplane Simpson method (mean ± SD) (58.5% ± 6.66% vs 66% ± 4.24%; P = 0.029). These results are not related with age, gender, degree of lipodystrophy, dyslipidemia, hyperinsulinism, and ART duration or the use of single antiretroviral classes. CONCLUSIONS: Vertically infected HIV children and adolescents show an increased thickness of EAT and IMT, expression of potentially increased CV risk. They also show an impaired systolic function.

Heart rate during exercise: mechanisms, behavior, and therapeutic and prognostic implications in heart failure patients with reduced ejection fraction.

Exercise intolerance is a typical manifestation of patients affected by heart failure with reduced ejection fraction (HFrEF); however, the relationship among functional capacity, mortality, and exercise-induced heart rate response during exercise remains unclear in either sinus rhythm or atrial fibrillation subjects. Heart rate increase during incremental load exercise has a typical pattern in normal subjects, whereas it is commonly compromised in HFrEF patients, mainly due to the imbalance of the autonomic nervous system. In the present review, we aim to describe the behavior of heart rate during exercise in normal subjects and in HFrEF patients in sinus rhythm and atrial fibrillation, understanding and explaining the mechanism leading to a different exercise performance and functional limitation. Moreover, the role of chronotropic incompetence and the need of standardizing the cutoff criteria are also discussed in order to clarify the clinical importance, the prognostic relevance, and the potential therapeutic implications of this condition. Looking into the relative contribution and interaction of heart rate response during exercise might represent an important issue to guide individualized therapeutic interventions and prognostic assessment in HFrEF patients.

Efficacy and safety of prolonged dual antiplatelet therapy: a meta-analysis of 15 randomized trials enrolling 85 265 patients.

AIMS: The optimal duration of dual antiplatelet therapy (DAPT) in patients with ischaemic cardiovascular (CV) disease is still debated. Previous meta-analyses reported conflicting results about prolonged DAPT on mortality and major CV events. Aim of this study was to assess the effects of prolonged vs. no/short-term DAPT on myocardial infarction (MI), stroke, bleeding, and mortality. METHODS AND RESULTS: Trial inclusion criteria were: randomization to prolonged duration vs. no/short DAPT; reporting of at least one outcome among overall and CV death, MI, stroke, major non-fatal, fatal, and intracranial bleeding. Fifteen randomized studies including 85 265 patients were included. Prolonged DAPT, compared with no or short DAPT, significantly reduced MI (RR: 0.785, 95% CI: 0.729-0.845, P < 0.001) and stroke (RR: 0.851, 95% CI: 0.754-0.959, P = 0.008), but had no effect on overall (RR: 0.989, 95% CI: 0.921-1.061, P = 0.751) or CV (RR: 0.951, 95% CI: 0.872-1.037, P = 0.258) mortality. Prolonged DAPT significantly increased major non-fatal (RR: 1.690, CI: 1.322-2.159, P < 0.001), but not intracranial or fatal bleeding (RR: 1.236, CI: 0.899-1.698, P = 0.192, RR: 1.069, CI: 0.760-1.503, P = 0.703; respectively). The effects of DAPT were similar to those reported in the overall analysis in patients with stable CV disease, whereas in those with unstable CV disease only the significant reduction of stroke was not confirmed. Dual antiplatelet therapy prolonged beyond 1 year significantly reduced MI but not stroke, all-cause, or CV death. It significantly increased the risk of major non-fatal bleeding, with no difference in intracranial and fatal bleeding. CONCLUSION: Prolonged DAPT significantly reduced ischaemic CV events but not mortality. Even if a significant increase of major non-fatal bleeding was detected, no increased risks of intracranial and fatal bleeding were observed.

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.

Prognostic role of transthoracic echocardiography in patients affected by heart failure and reduced ejection fraction.

Heart failure with reduced ejection fraction is a common and malignant condition, which recognizes a lot of causes and that carries a poor long-term prognosis. All patients with reduced left ventricular ejection fraction, both asymptomatic and symptomatic, should be evaluated with transthoracic echocardiography as a depth analysis of first level, due to its characteristics of accuracy, availability, safety and low costs. In fact, echocardiography is an essential tool to establish not only the diagnosis, but also the aetiology and the understanding pathophysiology of heart failure. Moreover, by the new more sensitive and more specific echocardiographic technologies, such as tissue Doppler imaging or strain rate or speckle tracking or three-dimensional echocardiography, it is possible to identify other recognized high-risk parameters associated with adverse outcome, which are useful to guide therapy and follow-up management of heart failure patients. Therefore, this review would underline the prognostic role of some echocardiographic parameters in the evaluation and management of patients with heart failure and reduced ejection fraction.

Reduction of lymphocyte G protein-coupled receptor kinase-2 (GRK2) after exercise training predicts survival in patients with heart failure.

BACKGROUND: Increased cardiac G protein-coupled receptor kinase-2 (GRK2) expression has a pivotal role at inducing heart failure (HF)-related ß-adrenergic receptor (ßAR) dysfunction. Importantly, abnormalities of ßAR signalling in the failing heart, including GRK2 overexpression, are mirrored in circulating lymphocytes and correlate with HF severity. Exercise training has been shown to exert several beneficial effects on the failing heart, including normalization of cardiac ßAR function and GRK2 protein levels. In the present study, we evaluated whether lymphocyte GRK2 levels and short-term changes of this kinase after an exercise training programme can predict long-term survival in HF patients. METHODS: For this purpose, we prospectively studied 193 HF patients who underwent a 3-month exercise training programme. Lymphocyte GRK2 protein levels, plasma N-terminal pro-brain natriuretic peptide, and norepinephrine were measured at baseline and after training along with clinical and functional parameters (left ventricular ejection fraction, NYHA class, and peak-VO2). Cardiac-related mortality was evaluated during a mean follow-up period of 37 ± 20 months. RESULTS: Exercise was associated with a significant reduction of lymphocyte GRK2 protein levels (from 1.29 ± 0.52 to 1.16 ± 0.65 densitometric units, p < 0.0001). Importantly, exercise related changes of GRK2 (delta values) robustly predicted survival in our study population. Interestingly, HF patients who did not show reduced lymphocyte GRK2 protein levels after training presented the poorest outcome. CONCLUSIONS: Our data offer the first demonstration that changes of lymphocyte GRK2 after exercise training can strongly predict outcome in advanced HF.

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.

Endothelial dysfunction in type 2 diabetic patients with normal coronary arteries: a digital reactive hyperemia study.

BACKGROUND: To assess endothelial function (EF) in type 2 diabetic patients with angiographically normal coronaries compared to diabetic patients with obstructive coronary artery disease (CAD) and to non-diabetic patients, with and without CAD. METHODS: One hundred eighty-three patients undergoing coronary angiography were divided in: group 1 with diabetes mellitus (DM) and CAD (n = 58); group 2 with DM without CAD (n = 58); group 3 with CAD without DM (n = 31) and group 4 without CAD and DM (n = 36). EF was assessed by reactive hyperemia index (RHI) using a fingertip peripheral arterial tonometry and compared to values obtained in 20 healthy volunteers. RESULTS: RHI was significantly lower in patients with DM compared to patients without DM (1.69 ± 0.38 vs 1.84 ± 0.44; p = 0.019). RHI was comparable among groups 1, 2 and 3, each value being significantly lower compared to group 4 (2 ± 0.44; p<0.001 vs group 1; p<0.005 vs group 2; p<0.002 vs group 3). At multivariate analysis DM and CAD were significant predictors of endothelial dysfunction (ED) (OR = 2.29; p = 0.012; OR = 2.76; p = 0.001, respectively), whereas diabetic patients (n = 116) CAD and glycated haemoglobin (HbA1c) were independent significant predictors of ED (OR = 3.05; p = 0.009; OR = 1.96; p = 0.004, respectively). Diabetic patients with ED (n = 67) had higher levels of HbA1c than diabetic patients with normal endothelial function (7.35 ± 0.97 vs 6.87 ± 0.90; p = 0.008) and RHI inversely correlated to HbA1c (p = 0.02; r = -0.210). CONCLUSIONS: Diabetic patients with and without CAD show significantly impaired peripheral vascular function compared to non-diabetic patients without CAD. ED in diabetic patients without CAD is comparable to that of patients with CAD but without DM. HbA1c is a weak independent predictor of ED.

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.

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.

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.

Effects of type 2 diabetes mellitus on coronary microvascular function and myocardial perfusion in patients without obstructive coronary artery disease.

PURPOSE: We assessed the impact of type 2 diabetes, in the presence of other major cardiovascular risk factors, on coronary microvascular function and myocardial perfusion in patients without obstructive coronary artery disease (CAD). METHODS: In this prospective study, 23 patients with type 2 diabetes and 26 nondiabetic patients matched for age, sex and other cardiovascular risk factors underwent a cold pressure test (CPT) and dipyridamole transthoracic echocardiography to determine their coronary flow (CF) ratio. Within 2 weeks, all diabetic patients also underwent dipyridamole-rest myocardial perfusion single-photon emission (MPS) CT. None of the patients with or without diabetes had significant CAD on invasive coronary angiography. RESULTS: The CPT-CF ratio was significantly lower in diabetic patients than in nondiabetic patients (1.46 ± 0.26 vs. 1.71 ± 0.32, p = 0.006) and was correlated significantly with fasting glycaemia (r = -0.35, p = 0.01), but not with glycated haemoglobin. The dipyridamole-CF ratio was also lower in diabetic patients than in nondiabetic patients (2.38 ± 0.74 vs. 2.75 ± 0.49, p = 0.04). On MPS imaging, 5 diabetic patients (22%) had stress-induced ischaemia and the remaining 18 (78%) had normal myocardial perfusion. The dipyridamole-CF ratio was not different in patients with and without reversible defects (2.3 ± 1.1 vs. 2.4 ± 0.6, p = 0.97). CONCLUSION: Coronary microvascular function is impaired in type 2 diabetic patients without significant CAD, compared to nondiabetic patients with similar other cardiovascular risk factors. In the majority of diabetic patients, microvascular dysfunction is associated with normal myocardial perfusion.

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

Cardiac sympathetic activity can be assessed by (123)I-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.

Myocardial perfusion scintigraphy and echocardiography for detecting coronary artery disease in hypertensive patients: a meta-analysis.

PURPOSE: This meta-analysis summarized the accuracy of stress myocardial perfusion scintigraphy (MPS) and stress echocardiography for the diagnosis of coronary artery disease (CAD) in patients with arterial hypertension. METHODS: We searched for studies in which stress MPS or stress echocardiography were performed to detect CAD in hypertensive patients, with coronary angiography used as the reference test, published from January 1980 to December 2010. Studies performed in patients with known CAD, acute coronary syndrome and previous revascularization procedures were excluded. RESULTS: Of 1,263 studies, 13 met the inclusion criteria. Pooled summary estimates showed that stress MPS had a sensitivity of 0.90 [95% confidence interval (CI) 0.82-0.95] and a specificity of 0.63 (95% CI 0.53-0.72). For stress MPS, the area under the curve (AUC) at the summary receiver-operating characteristic (SROC) graph was 0.83 (95% CI 0.80-0.86). At meta-regression analysis, the presence of positive stress electrocardiography as inclusion criterion was the only significant effect modifier (p < 0.01). Pooled summary estimates showed that stress echocardiography had a sensitivity of 0.77 (95% CI 0.69-0.83) and a specificity of 0.89 (95% CI 0.83-0.93). For stress echocardiography, the AUC at SROC was 0.91 (95% CI 0.88-0.93). At the meta-regression analysis no significant effect modifier was detected. CONCLUSION: MPS has high sensitivity for detecting CAD in hypertensive patients, with specificity comparable to that reported in the general population, whereas stress echocardiography shows higher specificity but substantially reduced sensitivity compared to MPS.