Mario Petretta

Effects of converting enzyme inhibition on heart period variability in patients with acute myocardial infarction.

Heart period variability provides useful prognosticinformation on autonomic cardiac control, and a strong association has been demonstrated after myocardial infarction (MI) between cardiac mortality, sudden death, and reduced total power, ultralow-frequency (ULF) power, and very-lowfrequency (VLF) power. Converting enzyme inhibitors are widely used in MI patients, but their influence on heart period variability emains to be defined. Methods and ResultsTime- and frequency-domain measures of heart period variability were calculated from 24-hour Holter monitoring in 40 patients with a first uncomplicated MI. After baseline examination between 48 and 72 hours after symptom onset, patients were randomly assigned to placebo or captopril administration, and on the third day, 24- hour Holter monitoring was repeated. No changes in time and frequency domain were detectable after placebo. After captopril, the SD of all normal RR (NN) intervals (SDNN) increased from 90±29 to 105±30 milliseconds (P < .01); the SD of the average NN intervals for all 5-minute segments (SDANN index) and the mean of the SDs of all NN intervals for all 5-minute segments (SDNN index) also increased from 74±24 to 90±26 milliseconds (P < .01) and from 45±17 to 49±15 milliseconds (P < .05), respectively. The root mean square successive difference (r-MSSD) and the percent of differences between adjacent NN intervals >50 milliseconds (pNN50) remained unchanged. In regard to frequency-domain measures, after captopril, total power (ln unit) increased from 8.28±0.42 to 8.47±0.30 (P < .01); considering the frequency bands, a significant increase was observed in ULF (P < .01), VLF (P < .05), and low-frequency (LF) power (P < .05), whereas high-frequency (HF) power remained unchanged. ConclusionsThis study supports the hypothesis that the renin-angiotensin system modulates the amplitude of ULF and VLF power. Furthermore, it demonstrates that in MI patients, converting enzyme inhibition favorably modifies measures of heart period variability strongly associated with a poor prognosis.

Impact of gender in primary prevention of coronary heart disease with statin therapy: A meta-analysis

BACKGROUND Evidence of lipid-lowering from clinical trials that included women is adequate to support their use in secondary prevention in women with known coronary disease. However the role of statin therapy in primary prevention is still controversial, in particular for female gender. The aim of our study is to perform a meta-analysis comparing by gender the cardiovascular outcomes related to statin therapy in primary prevention. METHODS We performed a meta-analysis including 8 randomized controlled trials (19,052 and 30,194 men, mean follow-up 3.9 years) that assessed the cardiovascular outcomes related to statin therapy, including studies that provided sex-specific results. MEDLINE and the Cochrane Database, were searched for articles published in English and other languages up to March 2008. RESULTS Statins do not appear to have a beneficial effect on total mortality for both men and women in primary prevention over the 2.8- to 5.3 year study period (men: 95% Confidence Interval (CI) 0.83-1.04; comparison p = 0.22; women: 0.96; CI 0.81-1.13; p = 0.61). Statin therapy reduced the risk of coronary heart disease (CHD) events in men (0.59; CI 0.48-0.74; p = 0.0001), however in women this risk reduction was weakly significant (0.89 CI 0.79-1.00; p = 0.05) and disappeared when in sensitivity analysis, trials not entirely of primary prevention were excluded (HPS, PROSPER) (0.95 CI 0.78-1.16; comparison p = 0.562). CONCLUSIONS Our study showed that statin therapy reduced the risk of CHD events in men without prior cardiovascular disease, but not in women. Statins did not reduce the risk of total mortality both in men and women.

Intensive training and cardiac autonomic control in high level athletes

PURPOSE We aimed to evaluate in a longitudinal study the effect of intensive training on cardiac autonomic control in athletes using 24-h heart rate variability analysis. METHODS Time and frequency domain measures of heart rate variability were calculated from 24-h Holter monitoring in 15 high level bicyclists (mean age 21 +/- 4 yr) after 1 month of detraining and after 5 months of vigorous training. At the same times echocardiographic left ventricular mass and dimensions and maximal oxygen consumption (VO2max) were assessed. RESULTS In detrained athletes, VO2max values, left ventricular mass and dimensions, and time and frequency domain measures of vagal modulation of heart rate were higher than in a group of untrained subjects of similar age while heart rate and the low-to-high frequency ratio were lower, indicating an enhanced vagal modulation of heart rate in athletes as compared with that in control subjects. After 5 months of vigorous training, left ventricular mass and dimensions and VO2max increased in athletes, while heart rate decreased further. In contrast, no changes were detectable in time and frequency domain measures of heart rate variability over the entire 24-h and in both waking and sleeping hours. CONCLUSIONS This study demonstrates that an increased cardiac vagal control is detectable in detrained athletes; however, after intensive training, despite a significant decrease in heart rate, time and frequency domain measures of heart rate variability reflecting cardiac vagal control remain unchanged. Thus, other mechanisms than changes in cardiac autonomic control could be involved in determining the profound bradycardia of athletes.

Independent and incremental prognostic value of heart rate variability in patients with chronic heart failure

BACKGROUND Decreased heart rate variability (HRV), indicating derangement in cardiac autonomic control, has been reported in patients with chronic heart failure. However, the independent and incremental prognostic value of HRV over clinical data and measures of left ventricular dysfunction has been less thoroughly investigated. This study was designed to evaluate the predictive value of HRV and Poincaré plots as assessed by 24-hour Holter recording in patients with chronic heart failure. METHODS Ninety-seven patients, mean age 55 +/- 13 years, with radionuclide left ventricular ejection fraction </=40% underwent echocardiographic examination and 24-hour Holter recording. Heart failure was caused by coronary artery disease in 57 patients (59%) and idiopathic dilated cardiomyopathy in 40 (41%). RESULTS During follow-up (39 +/- 18 months), 32 cardiac deaths occurred. By Cox multivariate analysis, significant predictors of death were left ventricular end-systolic volume (hazard ratio 1.04), low- to high-frequency ratio (hazard ratio 0.09), percentage of differences between successive normal R-R intervals >50 ms (hazard ratio 0.93), and age (hazard ratio 1.06). Furthermore, HRV analysis improved (P <. 001) the prognostic power of a model including clinical and echocardiographic data, left ventricular ejection fraction, and ventricular arrhythmias at Holter recording, whereas the inclusion of Poincaré plots did not add further predictive value. CONCLUSIONS Our investigation demonstrated that HRV has independent and incremental prognostic value in patients with chronic heart failure and seems useful to stratify patients at high risk of cardiac death.

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.

Successful coronary revascularization improves prognosis in patients with previous myocardial infarction and evidence of viable myocardium at thallium-201 imaging

Abstract. The role of coronary revascularization of dysfunctional myocardium with preserved thallium-201 uptake in determining the prognosis in patients after myocardial infarction remains to be defined. This study was designed to evaluate the effects of successful revascularization on survival and left ventricular (LV) function in patients with previous myocardial infarction and evidence of dysfunctional but still viable myocardium at rest-redistribution 201Tl imaging. Seventy-six consecutive patients with LV dysfunction related to previous myocardial infarction and evidence of viable myocardium at rest-redistribution 201Tl tomography were followed for 17±8 months. LV ejection fraction (EF) was assessed by radionuclide angiography at baseline and after 13±2 months. Thirty-nine patients were revascularized (group A) and 37 treated medically (group B). During the follow-up there were nine cardiac deaths. Survival rate was 97% in group A and 66% in group B (P<0.01). By Cox multivariate analysis, the extent of viable myocardium was the best predictor of cardiac death (χ2=8.67, P<0.01) and provided additional information to clinical and functional data (P<0.01). The inclusion of revascularization as a variable improved the global χ2 of the model from 14.1 to 21.9 (P<0.01). At follow-up, EF had improved by ≥5% in 16 patients. By multivariate logistic analysis, the extent of viable myocardium was the best predictor of EF improvement (χ2=15.49, P<0.001) and provided additional information to clinical and functional data (P<0.01). The inclusion of revascularization as a variable improved the global χ2 of the model from 16.8 to 22.5 (P<0.01). These results demonstrate that the total extent of dysfunctional myocardium with preserved 201Tl uptake is the strongest predictor of cardiac death in patients after myocardial infarction. Successful revascularization of dysfunctional but viable myocardium improves survival and LVEF in such patients.

Review and metaanalysis of the frequency of familial dilated cardiomyopathy.

Several studies have investigated the frequency of familial dilated cardiomyopathy (FDC). However, no systematic review and meta-analysis on this topic are available. Therefore, using the PubMed, MEDLINE, Cochrane, and the ISI Web of Science databases, relevant reports published through December 2010 were identified. For the summation of prevalence findings, prevalence point estimates and 95% confidence intervals were computed using the logit transformation formula. An aggregate estimate of clinically confirmed FDC of 23% (95% confidence interval 0.17 to 0.31) was found. However, the prevalence rates reported across these studies varied widely, ranging from 2% to 65%, and the analysis showed very high heterogeneity (Q = 295, p <0.001, I(2) = 93%). Meta-regression analysis between logit event rate and year of publication explained 23% of between-study variance (p <0.05). Cumulative meta-analysis confirmed the influence of year of publication on the reported prevalence of FDC among the different studies. However, most of the observed heterogeneity may be explained by the fact that the various studies used different preselected criteria for the diagnosis of FDC. In conclusion, data obtained from trials performed using standardized criteria are needed to better define the true prevalence of FDC.

Direct comparison of technetium 99m—sestamibi and technetium 99m—tetrofosmin cardiac single photon emission computed tomography in patients with coronary artery disease

BackgroundTechnetium 99m-labeled sestamibi and tetrofosmin tomography have shown high diagnostic accuracy in the detection of coronary artery disease (CAD). However, few data are available comparing sestamibi and tetrofosmin imaging in the same patients. The aim of the study was to determine the image quality of the two tracers and to compare the results of exercise sestamibi and tetrofosmin tomography in the same patients.MethodsThe results of exercise-rest sestamibi and tetrofosmin myocardial tomography were compared in 32 patients with suspected or known CAD who underwent coronary angiography. Image quality was evaluated subjectively. Regional tracer distribution was visually assessed and quantitatively measured in 22 segments/patient.ResultsAt coronary angiography 7 patients had normal coronary vessels, 11 single-vessel, and 14 multivessel CAD (≥50% luminal stenosis). Image quality judged visually was comparable with the two tracers. Heart/lung and heart/liver ratios for sestamibi and tetrofosmin were not different. At visual analysis, 68% of the patients with CAD had abnormal findings with sestamibi and 76% with tetrofosmin (p=NS). At quantitative analysis, 92% of the patients with CAD had abnormal findings with sestamibi and 96% with tetrofosmin (p=NS). At both visual and quantitative analyses, sensitivity, specificity, and diagnostic accuracy in the detection of individual stenosed vessels were not different between the two tracers. Moreover, for both tracers sensitivity, specificity, and diagnostic accuracy in the detection of diseased vessels were significantly higher (all p<0.05) at quantitative compared with visual analysis. Finally, defect size and severity were similar for the two tracers.ConclusionsExercise-rest sestamibi and tetrofosmin tomography yielded images of comparable quality and provided similar results in the identification of patients with CAD and in the detection of the individual stenosed coronary vessels.

Power spectral analysis of heart period variability in hypertensive patients with left ventricular hypertrophy.

This study aimed to characterize sympathovagal balance by heart period power spectrum analysis in hypertensive patients with echocardiographic evidence of left ventricular hypertrophy. Twenty ambulatory patients (11 men and 9 women), aged 50 +/- 10 years, with established essential hypertension and echocardiographic left ventricular hypertrophy, performed 24-h blood pressure monitoring and electrocardiogram Holter recording on 2 consecutive days. Twenty age- and sex-matched normal subjects comprised the control group. Power spectrum analysis, performed using the fast Fourier transform algorithm, demonstrated lower values of low and high frequency power in hypertensives than in controls, while ultralow and very low frequency power were similar in the two groups. Very low frequency, low frequency, and high frequency power increased during the night in both groups, showing a similar circadian pattern. We found a direct correlation between daytime systolic (r = 0.51; P < .05) and diastolic (r = 0.52; P < .05) blood pressure and left ventricular mass index. Moreover, negative correlations were found between left ventricular mass index and low frequency (r = -0.47; P < .05) and high frequency power (r = -0.47; P < .05). There was a direct correlation between nighttime decrease in systolic blood pressure and nighttime increase in high frequency power (r = 0.45; P < .05). As 24-h low frequency and high frequency power, obtained using the Fourier transform algorithm, both reflect the parasympathetic modulation of heart rate, our results demonstrate that hypertensive patients with left ventricular hypertrophy are characterized by a sympathovagal imbalance with a reduction of vagal tone that is more evident with increasing severity of hypertension.

Effects of captopril treatment on left ventricular remodeling and function after anterior myocardial infarction: comparison with digitalis.

The effects of captopril and digoxin treatment on left ventricular remodeling and function after anterior myocardial infarction were evaluated in a randomized unblinded trial. Fifty-two patients with a first transmural anterior myocardial infarction and a radionuclide left ventricular ejection fraction less than 40% were randomly assigned to treatment with captopril (Group A) or digoxin (Group B). The two groups had similar baseline hemodynamic, coronary angiographic, echocardiographic and radionuclide angiographic variables. Among the 40 patients (20 in each group) who were followed up for 1 year, echocardiographic end-diastolic and end-systolic volumes were unmodified in Group A and global wall motion index was improved (p less than 0.01); in Group B, end-diastolic and end-systolic volumes increased (p less than 0.001 for both) and global wall motion index was unchanged. Rest radionuclide ejection fraction increased significantly in both groups (p less than 0.001, Group A; p less than 0.005, Group B). A comparison of the changes in the considered variables between the two groups after 1 year of treatment showed a difference in end-diastolic (p less than 0.005) end-systolic volumes (p less than 0.001) and global wall motion index (p less than 0.005) without differences in radionuclide ejection fraction, which improved to a similar degree in both groups. The results of this study suggest that captopril therapy, started 7 to 10 days after symptom onset in patients with anterior myocardial infarction and an ejection fraction less than 40%, improves both left ventricular remodeling and function and prevents left ventricular enlargement and in these patients performs better than digitalis.