Donatella Ruggiero

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.

A meta-analysis reporting effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in patients without heart failure.

OBJECTIVES The goal of the study was to assess the effects of angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) on the composite of cardiovascular (CV) death, myocardial infarction (MI), and stroke, and on all-cause death, new-onset heart failure (HF), and new-onset diabetes mellitus (DM) in high-risk patients without HF. BACKGROUND ACE-Is reduce CV events in high-risk patients without HF whereas the effects of ARBs are less certain. METHODS Twenty-six randomized trials comparing ARBs or ACE-Is versus placebo in 108,212 patients without HF were collected in a meta-analysis and analyzed for the risk of the composite outcome, all-cause death, new-onset HF, and new-onset DM. RESULTS ACE-Is significantly reduced the risk of the composite outcome (odds ratio [OR]: 0.830 [95% confidence interval (CI): 0.744 to 0.927]; p = 0.001), MI (OR: 0.811 [95% CI: 0.748 to 0.879]; p < 0.001), stroke (OR: 0.796 [95% CI: 0.682 to 0.928]; p < 0.004), all-cause death (OR: 0.908 [95% CI: 0.845 to 0.975]; p = 0.008), new-onset HF (OR: 0.789 [95% CI: 0.686 to 0.908]; p = 0.001), and new-onset DM (OR: 0.851 [95% CI: 0.749 to 0.965]; p < 0.012). ARBs significantly reduced the risk of the composite outcome (OR: 0.920 [95% CI: 0.869 to 0.975], p = 0.005), stroke (OR: 0.900 [95% CI: 0.830 to 0.977], p = 0.011), and new-onset DM (OR: 0.855 [95% CI: 0.798 to 0.915]; p < 0.001). CONCLUSIONS In patients at high CV risk without HF, ACE-Is and ARBs reduced the risk of the composite outcome of CV death, MI, and stroke. ACE-Is also reduced the risk of all-cause death, new-onset HF, and new-onset DM. Thus, ARBs represent a valuable option to reduce CV mortality and morbidity in patients in whom ACE-Is cannot be used.

The Prognostic Value of Normal Stress Cardiac Magnetic Resonance in Patients with Known or Suspected Coronary Artery Disease: A Meta-analysis

Background—Ischemia detection with stress cardiac magnetic resonance (CMR) is typically based on induction of either myocardial perfusion defect or wall motion abnormality. Single-center studies have shown the high value of stress CMR for risk stratification. The aim of this study was to define the prognostic value of stress CMR for prediction of adverse cardiac events in patients with known or suspected coronary artery disease. Methods and Results—Studies published between January 1985 and April 2012 were identified by database search. We included studies using stress CMR to evaluate subjects with known or suspected coronary artery disease and providing primary data on clinical outcomes of nonfatal myocardial infarction or cardiac death with a follow-up time ≥3 months. Total of 14 studies were finally included, recruiting 12 178 patients. The negative predictive value for nonfatal myocardial infarction and cardiac death of normal CMR was 98.12% (95% confidence interval, 97.26–98.83) during a weighted mean follow-up of 25.3 months, resulting in estimated event rate after a negative test equal to 1.88% (95% confidence interval, 1.17–2.74). The corresponding annualized event rate after a negative test was 1.03%. Comparable negative predictive values for major coronary events were obtained in studies considering the absence of inducible perfusion defect compared with those evaluating the absence of inducible wall motion abnormality (98.39% versus 97.31%, respectively; P=0.227 by meta-regression analysis). Conclusions—Stress CMR has a high negative predictive value for adverse cardiac events, and the absence of inducible perfusion defect or wall motion abnormality shows a similar ability to identify low-risk patients with known or suspected coronary artery disease.

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.

Prognostic role of myocardial single photon emission computed tomography in the elderly

The increase in average life expectancy will move the burden of coronary artery disease (CAD) to older patients. Myocardial perfusion imaging by single photon emission computed tomography (SPECT) has been extensively validated for diagnosis and prognostic evaluation in large population series. Yet, its use is usually limited in elderly patients in whom, despite increased absolute cardiovascular risk, diagnostic and therapeutic work-up is often underperformed. American College of Cardiology/American Heart Association guidelines recommend exercise ECG testing as the initial noninvasive method for assessment of CAD in patients with a normal or near-normal resting ECG, regardless of age. However, a considerable proportion of elderly patients is unable to reach an adequate workload during the exercise test and the majority of those undergoing for standard exercise treadmill score are classified as intermediate risk. In elderly patients, SPECT imaging may provide valuable diagnostic and prognostic information for clinical management. In particular, normal or near normal SPECT identifies elderly patients at low risk of major adverse cardiac events at the short-term follow-up.

Molecular imaging of atherosclerosis in translational medicine

Functional characterization of atherosclerosis is a promising application of molecular imaging. Radionuclide-based techniques for molecular imaging in the large arteries (e.g. aorta and carotids), along with ultrasound and magnetic resonance imaging (MRI), have been studied both experimentally and in clinical studies. Technical factors including cardiac and respiratory motion, low spatial resolution and partial volume effects mean that noninvasive molecular imaging of atherosclerosis in the coronary arteries is not ready for prime time. Positron emission tomography imaging with fluorodeoxyglucose can measure vascular inflammation in the large arteries with high reproducibility, and signal change in response to anti-inflammatory therapy has been described. MRI has proven of value for quantifying carotid artery inflammation when iron oxide nanoparticles are used as a contrast agent. Macrophage accumulation of the iron particles allows regression of inflammation to be measured with drug therapy. Similarly, contrast-enhanced ultrasound imaging is also being evaluated for functional characterization of atherosclerotic plaques. For all of these techniques, however, large-scale clinical trials are mandatory to define the prognostic importance of the imaging signals in terms of risk of future vascular events.

N-terminal pro-b-type natriuretic peptide and left atrial function in patients with congestive heart failure and severely reduced ejection fraction.

AIMS Amino-terminal portion of pro-B-type natriuretic peptide (NT-pro-BNP) is a valuable diagnostic and prognostic marker in congestive heart failure (CHF). In CHF patients, elevation of natriuretic peptide levels correlate with decreased left ventricular (LV) ejection fraction (EF) and increased left atrial (LA) volumes, but a correlation with LA function that is a determinant of haemodynamic and clinical status in CHF with independent prognostic value has never been investigated. Aim of this study was to evaluate the relationship between cardiac neurohormonal activation and LA function in patients with CHF due to dilated cardiomyopathy. METHODS AND RESULTS One hundred and one patients (86% males; mean age, 64 ± 11 years) with dilated ischaemic or non-ischaemic cardiomyopathy, LV EF ≤45% (mean LV EF, 33 ± 8%), and New York Heart Association class II-IV underwent transthoracic echocardiography to evaluate LA fractional active and total emptying from M- and B-Mode images, and, on the same day, venous blood sample collection to dose NT-pro-BNP. By univariate analyses, NT-pro-BNP significantly correlated to age, LA dimensions, LA function indexes, EF, and functional class. At multivariate analysis, LV EF and M- or B-Mode indexes of LA function were the only independent predictors of NT-pro-BNP values. A NT-pro-BNP cut-off of 1480 pg/mL identified LA dysfunction with 89% specificity and 54% sensitivity. CONCLUSION In CHF patients with severely impaired systolic function, NT-pro-BNP levels reflect LA and LV dysfunction. These data should prompt studies to investigate the relationship between changes of LA function and NT-pro-BNP levels and their clinical value as prognostic and therapeutic targets in CHF.

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.

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.