Andrea Petretta

Calcium channel blockers and cardiovascular outcomes: a meta-analysis of 175 634 patients

Objective The aim of this study was to assess the effect of calcium channel blocker (CCB) treatment, compared with other drugs or placebo/top of therapy, on all-cause mortality, cardiovascular death, major cardiovascular events, heart failure, myocardial infarction and stroke. Methods We performed a meta-analysis of randomized controlled trials that compared a long-acting calcium channel blocker with another drug or placebo/top of therapy and that assessed all-cause mortality and cardiovascular events. Results We included 27 trials (175 634 patients). The risk of all-cause death was reduced by dihydropyridine CCBs [odds ratio (OR) 0.96; 95% confidence interval (CI) 0.93–0.99; comparison P = 0.026; heterogeneity P = 0.87)] without influence of placebo trials. The risk of heart failure was increased by CCBs compared with active treatment (OR 1.17; 95% CI 1.11–1.24; comparison P = 0.0001; heterogeneity P = 0.0001), and it was decreased when compared with placebo (OR 0.72; 95% CI 0.59–0.87; comparison P = 0.001; heterogeneity P = 0.77), also in the subgroup of coronary artery disease patients (OR 0.76; 95% CI 0.61–0.95; comparison P = 0.01; heterogeneity P = 0.29). CCBs did not increase the risk of myocardial infarction (OR 1; 95% CI 0.95–1.04; comparison P = 0.83, heterogeneity P = 0.004), cardiovascular death (OR 0.97; 95% CI 0.93–1.02; comparison P = 0.24; heterogeneity P = 0.16), major cardiovascular events (OR 0.97; 95% CI 0.90–1.06; comparison P = 0.53; heterogeneity P = 0.0001). CCBs decreased the risk of fatal or nonfatal stroke (OR 0.86; 95% CI 0.82–0.90; comparison P = 0.0001, heterogeneity P = 0.12), also, when compared with angiotensin-converting enzyme inhibitors (OR 0.87; 95% CI 0.78–0.97; comparison P = 0.016; heterogeneity P = 0.48). Conclusion Our study demonstrates that CCBs reduce the risk of all-cause mortality compared with active therapy and prevent heart failure compared with placebo. Furthermore, with the inclusion of recent trials, we confirm that they reduce the risk of stroke, also in comparison to angiotensin-converting enzyme inhibitors and do not increase the risk of cardiovascular death, myocardial infarction and major cardiovascular events.

Effects of AT1 receptor antagonism with candesartan on endothelial function in patients with hypertension and coronary artery disease.

Endothelial dysfunction is a major determinant of atherosclerosis and a negative prognostic factor in patients with coronary artery disease and hypertension. Recovery of endothelial dysfunction has been associated with improved prognosis in these patients. The aim of the present study was to verify whether antagonism of angiotensin II AT1 receptors with an angiotensin receptor blocker, candesartan, improved endothelial function in patients with hypertension, stable coronary artery disease, and endothelial dysfunction. We studied 26 patients who were receiving β‐blockers with optimal blood pressure control, in a randomized, double blind study. Patients were randomized to placebo (n=13) or to candesartan 16 mg/d (n=13) for 2 months. Endothelial function was assessed by ultrasound using hyperemic flow‐mediated dilation of the brachial artery. Mean arterial blood pressure was unchanged in both groups (from 93.3±9.2 to 93.2±17.3 mm Hg in the candesartan group and from 101.3±14.2 to 102.3±13.9 mm Hg in the placebo group; both P=ns). Maximal blood flow was similar between placebo and candesartan groups at baseline and at the end of the study, whereas flow‐mediated dilation significantly increased in the candesartan group (from 5.27%±1.69% to 7.15%±2.67%; P=0.01) but remained unchanged in the placebo group (from 4.49%±1.97% to 5.88%±2.30%; P=ns). AT1 receptor antagonism with candesartan, in addition to β‐blocker therapy, improves endothelial function in high‐risk hypertensive patients.

Rest-redistribution 201-Thallium single photon emission computed tomography predicts myocardial infarction and cardiac death in patients with ischemic left ventricular dysfunction

The prognostic role of rest-redistribution 201-Thallium imaging has not been extensively investigated in patients with left ventricular ischemic dysfunction. Objective The aim of this study was to evaluate the ability of rest-redistribution 201-Thallium single photon emission computed tomography to predict cardiac death and occurrence of acute myocardial infarction in patients with ischemic mild-to-moderate left ventricular dysfunction. Methods One-hundred and twenty-six patients with chronic coronary artery disease and mean left ventricular ejection fraction 39 ± 11% were followed-up for 30 ± 17 months after a rest-redistribution 201-Thallium imaging single photon emission computed tomography. Cardiac death and acute myocardial infarction were considered as major cardiac events. Results During the follow up, 11 (9%) cardiac deaths and 9 (7%) acute myocardial infarctions occurred. The only variable showing significant difference between patients with and without events was the number of severe irreversible defects (1.7 ± 1.9 versus 0.9 ± 1.2, respectively; P = 0.02). By Kaplan–Meier analysis, the presence of three or less, or more than three severe defects was selected as the best cutoff to identify patients with longer event-free survival from cardiac death or acute myocardial infarction (log rank 19.84; P < 0.0001). When only cardiac death was considered as clinical event, the presence of at least two severe defects best separated patients who died from those who survived (log rank 8.68; P = 0.0032). Conclusion Rest-redistribution 201-Thallium single photon emission computed tomography provides prognostic information in coronary patients with mild-to-moderate left ventricular dysfunction. The number of severe irreversible defects per patient is a powerful predictor of prognosis.

My warranty has expired: I need to be retested

The concept of warranty period, the duration of time during which the patient’s risk remains low, is appealing. However, some points remain to be resolved before its translation in the clinical arena. Methodological issues should be standardized in order to compare the results of studies in different patient populations. Also, the definition of a “normal” study should always take into consideration the history of prior revascularization, the achieved level of exercise, and the stressor used. The promise of warranty can be questioned by the patient’s baseline demographic and clinical characteristics and may also be influenced by life-style modification in the course of the follow-up. The “warranty period” concept should shift from data reflecting the time to a cardiac event to the development of ischemia, given an opportunity for intervention before a cardiac event occurs. In this context, clarify the role of serial imaging can be extremely useful, in particular to evaluate if and when retesting a patient after a normal scan.

Assessment of asynchrony by gated myocardial perfusion imaging improves patient management: Pro

The diagnostic and prognostic utility of gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) in patients with suspected or known coronary artery disease (CAD) is well established. In addition to myocardial perfusion and left ventricular (LV) function, gated SPECT allows the assessment of mechanical asynchrony that may occur during contraction or relaxation. The normal LV contracts in a coordinated behavior and most of the myocardial segments have nearly the same phase, with little more than 40 ms variation at the onset of electrical activation. Mechanical asynchrony refers to the abnormal prolongation of the timing of contraction or relaxation between the atrium and ventricle, between the right ventricle (RV) and LV or between different LV segments. LV asynchrony is often observed in patients with heart failure (HF), due to electrical conduction delay in some regions of the LV, which in turn leads to uncoordinated contraction and reduced cardiac efficiency. The prevalence of asynchrony depends on the methodology of measurement and characteristics of patients. The assessment of LV asynchrony is useful for the exploration of disease mechanism, selection of treatment, stratification of risk, and prediction of treatment response especially in HF patients who are eligible for cardiac resynchronization therapy (CRT). Phase analysis of timing of contraction has been used for many years with radionuclide ventriculography and is still an area of active research. The high-count yields of Tc-labeled agents make possible the acquisition of multiple gated SPECT studies with relatively high-count densities. Chen et al. developed a count-based method and the first-harmonic fast Fourier transform to extract the LV regional phase throughout the cardiac cycle using sestamibi gated SPECT in healthy subjects to obtain normal databases and dynamic displays for assessment of cardiac mechanic asynchrony. The normal phase image is close to a uniform distribution and the histogram is narrow and highly peaked, with the most frequent phase corresponding to the peak of the phase histogram. Four quantitative indices of LV asynchrony have been proposed: (1) phase standard deviation (SD); (2) histogram bandwidth (BW), which includes 95% of the elements in the phase distribution; (3) histogram skewness (S), which indicates the symmetry of the histogram; and (4) histogram kurtosis (K), with a higher peak within a narrower band indicates high K.

Radionuclide Imaging in Patients with Ischemic Heart Failure

Nuclear imaging procedures are well-established diagnostic tools in clinical cardiology, providing noninvasive information about myocardial perfusion, cardiac function and metabolism. Scintigraphic parameters provide relevant information that aids in everyday clinical decision making for referring physicians. In patients with coronary artery disease, the presence of myocardial necrosis, postischemic stunning and hibernation can determine left ventricular dysfunction leading to ischemic heart failure. The prognosis of these patients is still poor and the long-term results of medical management remain discouraging. It is now well established that ventricular dysfunction is often a reversible process and ventricular function may improve following myocardial revascularization. Patients with extensive areas of hibernation treated medically have a worse prognosis as compared to those who undergo revascularization with a similar extent of viable myocardium. Therefore, an accurate non-invasive assessment of myocardial viability with the preoperative differentiation between hibernation and stunning and irreversibly necrotic tissue is important for clinical decision-making to select patients candidates for revascularization. Radionuclide imaging techniques evaluating myocardial perfusion, cell membrane integrity, ventricular function and cardiac metabolism have demonstrated clinical utility in the assessment of myocardial viability and in predicting improvement of ventricular function and prognosis after coronary revascularization. Under certain conditions, when viable myocytes are subject to ischemia, prolonged alterations in regional or global left ventricular function may occur and this dysfunction may be completely reversible. This condition may be related to two pathophysiological states: stunned and hibernating myocardium. Stunned myocardium refers to the state of persistent regional dysfunction after a transient period of ischemia that has been followed by reperfusion, and is mainly present in acute coronary syndromes. Myocardial hibernation refers to persistent regional left ventricular dysfunction secondary to prolonged, subacute or chronic myocardial hypoperfusion under resting conditions in which myocytes remain viable but regional contractility is reduced to match the reduced blood supply (1, 2). It has been suggested that during hibernation a new state of equilibrium is reached between blood flow (oxygen supply) and contraction (oxygen demand) whereby myocardial necrosis is prevented. Therefore, hibernation is considered a protective response of decrease oxygen demand in the setting of decrease oxygen availability (3). Early studies suggested that resting blood flow is severely reduced in hibernating myocardium. However, more recent data obtained with quantitative measurements of myocardial blood flow indicate that during hibernation resting blood flow may be normal or only moderately reduced, with a disproportiona l decline in contractile function (4, 5). These findings suggest that