Including patients with diabetes mellitus or coronary artery bypass grafting decreases the association between heart rate variability and mortality after myocardial infarction

Background

Decreased heart rate variability (HRV) is often assumed to be associated with mortality in all patients after myocardial infarction (MI), independent of clinical factors or time after MI.

Method

HRV was determined from Holter tapes in the Cardiac Arrhythmia Suppression Trial (CAST). Patients were 71 ± 120 days after MI. A total of 735 pre-therapy tapes were analyzed in patients who had ventricular premature contractions (VPCs) suppressed on the first treatment. The period of follow-up was 362 ± 243 days (69 deaths). The association of clinical and demographic factors and 24-hour, daytime, and nighttime HRV to mortality in all patients, patients without coronary artery bypass graft (CABG) surgery between the qualifying MI and the Holter monitoring, and patients with neither CABG nor diabetes mellitus was determined with univariate Cox regression analysis.

Results

For the entire group and the subgroup without CABG, the strongest association was with increased daytime normalized high frequency power (NHF day). Further excluding patients with diabetes mellitus strengthened the association of HRV with mortality rate. Decreased natural logarithm (ln) 24-hour total and ultra low frequency (ULF) power were the strongest predictors of mortality. The best cutoff point for ln ULF for separating survivors and non-survivors was determined. After including a history of MI, congestive heart failure, or both as co-factors, ln ULF ≤7.85 identified patients at approximately 4-times the relative risk of mortality, but did not risk-stratify patients without prior MI or history of congestive heart failure.

Conclusions

HRV predicts mortality rate in a broad range of times after MI. Excluding patients with CABG after MI or with diabetes mellitus significantly strengthens the association of HRV with mortality. HRV measures beyond the peri-infarction period, with clinical factors, can identify subgroups at an elevated risk of mortality.     

Clinical and demographic determinants of heart rate variability in patients post myocardial infarction: insights from the cardiac arrhythmia suppression trial (CAST)

BACKGROUND: Clinical and demographic determinants of heart rate variability (HRV), an almost universal predictor of increased mortality, have not been systematically investigated in patients post myocardial infarction (MI). HYPOTHESIS: The study was undertaken to evaluate the relationship between pretreatment clinical and demographic variables and HRV in the Cardiac Arrhythmia Suppression Trial (CAST). METHODS: CAST patients were post MI and had > or =6 ventricular premature complexes/h on pretreatment recording. Patients in this substudy (n = 769) had usable pretreatment and suppression tapes and were successfully randomized on the first antiarrhythmic treatment. Tapes were rescanned; only time domain HRV was reported because many tapes lacked the calibrated timing signal needed for accurate frequency domain analysis. Independent predictors of HRV were determined by stepwise selection. RESULTS: Coronary artery bypass graft surgery (CABG) after the qualifying MI was the strongest determinant of HRV. The markedly decreased HRV associated with CABG was not associated with increased mortality. Ejection fraction and diabetes were also independent predictors of HRV. Other predictors for some indices of HRV included beta-blocker use, gender, time from MI to Holter, history of CABG before the qualifying MI, and systolic blood pressure. Decreased HRV did not predict mortality for the entire group. For patients without CABG or diabetes, decreased standard deviation of all NN intervals (SDANN) predicted mortality. Clinical and demographic factors accounted for 31% of the variance in the average of normal-to-normal intervals (AVGNN) and 13-26% of the variance in other HRV indices. CONCLUSIONS: Heart rate variability post MI is largely independent of clinical and demographic factors. Antecedent CABG dramatically reduces HRV. Recognition of this is necessary to prevent misclassification of risk in patients post infarct.     

Increased intra-QRS fragmentation in magnetocardiography as a predictor of arrhythmic events and mortality in patients with cardiac dysfunction after myocardial infarction

Introduction: Increased intra-QRS fragmentation score (FRA) in magnetocardiography (MCG) has shown association with sustained ventricular arrhythmias in post-MI patients suggesting its relation to arrhythmia substrate. The aim of this study was to investigate whether increased FRA in MCG predicts arrhythmic events and mortality after acute myocardial infarction (MI) with cardiac dysfunction.
Methods and Results: A series of 158 patients with acute MI and left ventricular ejection fraction (LVEF) <50% were studied. Their age was 60 ± 10 years and LVEF 40 ± 6%. MCG was registered and FRA was computed. For comparison, QRS duration in 12-lead ECG was measured. In a mean follow-up of 50 ± 15 months, 32 (20%) patients died and 18 (11%) had an arrhythmic event. Both arrhythmic event rate and all-cause mortality were significantly higher in patients with increased FRA (P < 0.001 for both). In contrast, increased QRS duration in ECG predicted all-cause mortality (P < 0.05) but not arrhythmic events. In multivariate analysis, FRA was an independent predictor of both arrhythmic events and all-cause mortality. Using a combined criterion of increased FRA and LVEF < 30% yielded positive and negative predictive accuracies of 50% and 91% for arrhythmic events.
Conclusion: In post-MI patients with left ventricular dysfunction, increased intra-QRS fragmentation in high-resolution magnetocardiography predicts arrhythmic events, whereas QRS duration in 12-lead ECG predicts all-cause mortality. Analysis of intra-QRS fragmentation by MCG may assist in guiding therapy of post-MI patients, for example, by selecting those who would benefit most from prophylactic implantable cardioverter-defibrillator therapy.     

Intensive home-based exercise training in cardiac rehabilitation increases exercise capacity and heart rate variability.

BACKGROUND: Reduced heart rate variability (HRV) is a risk factor for cardiac death. Animal studies have shown increased HRV and reduced mortality after physical training. We evaluated the change in exercise capacity and HRV in cardiac rehabilitation patients, randomised to routine or home-based intensive training. The design was prospective, stratified randomisation with pre-specified subgroup analysis. METHODS: Maximal bicycle exercise test and 24-h Holter were performed 1 (baseline), 4 and 12 months after myocardial infarction (MI) or coronary artery by-pass surgery (CABG). Patients were randomised to physical training either two (N) or six (I) times per week for 3 months Sixty-two patients (43 MI and 19 CABG patients) were evaluated. RESULTS: Exercise capacity increased significantly more after 3 months of training in group I (mean (S.E.)); 29.0 (3.4) vs. 7.2 (2.6) watts, P<0.001). One year later the difference in exercise capacity remained (26.5 (3.3) vs. 11.8 (3.8) watts, P<0.001). Global HRV measurements SDNN and SDANN increased significantly more in group I after training (17.1 (5.6) vs. 1.7 (3.7) and 16.2 (4.9) vs. 2.8 (3.1) ms, P<0.05) and 1 year later the differences were still significant. Subgroup analysis showed more pronounced HRV response in CABG than MI patients. CONCLUSION: Intensive exercise training in cardiac rehabilitation increases exercise capacity and global HRV, which could be of prognostic significance.     

Determinants of a reduced heart rate variability in chronic atrial fibrillation

Background: We aimed to evaluate whether clinical factors, which influence heart rate variability (HRV) in the presence of undisturbed sinus rhythm, have any associations with HRV in patients with permanent atrial fibrillation (AF). Methods: One hundred ninety‐seven consecutive patients with permanent AF were included (122 males, 75 females, aged 64 ± 11 years, range 25–85). In each patient a 24‐hour electrocardiographic recording was performed and an HRV fraction (HRVF)—the index based on scatter plot numerical processing—was calculated. Additionally, standard HRV measures were analyzed. Reduced HRVF was defined as its value lower than lower normal limit. Demographic and clinical factors were examined for their association with a reduced HRVF by means of a univariate and multivariate logistic regression analysis. Results: The reduced HRVF was associated with advanced age, clinical diagnosis of a previous MI or dilated cardiomyopathy, presence of diabetes, depressed left ventricular function, NYHA class > II, treatment regimen, use of digoxin, diuretics or antiarrhythmic agents, nonuse of beta‐blockers, and increased heart rate. The independent determinants that sustained after multivariate analysis were: heart rate (per 10 bpm increase, odds ratio 2.77 [1.88–4.07]), age (per 5 years increase 1.43 [1.1–1.85]), depressed left ventricular EF (<30% vs higher 2.26 [1.19–4.31]), and presence of diabetes (3.45 [1.1–10.85]). The HRVF correlated moderately with standard HRV measures. This index showed also the strongest correlation with left ventricular ejection fraction. Conclusion: We concluded that advanced age, left ventricular systolic dysfunction, increased heart rate, and presence of diabetes are cofactors of a reduced HRV in AF patients. Thus, the determinants of heart rate variability in the presence of atrial fibrillation are the same as those in sinus rhythm. Ann Noninvasive Electrocardiol 2011;16(4):321–326     

Heart rate variability decreased by coronary artery surgery has no prognostic value.

BACKGROUND: Decreased heart rate variability (HRV) may predict cardiac death after myocardial infarction (MI). Coronary artery bypass grafting (CABG) strongly decreases HRV, but improves survival. The aim of the study was to determine the prognostic value of HRV decreased by coronary surgery. DESIGN AND METHODS: Four-year follow-up was performed in 175 consecutive patients with HRV decreased by CABG (51) or MI (124). Mortality and secondary events rate were analysed. Decreased HRV, defined by the standard deviation of mean RR interval (SDNN) < 100 ms, was detected by a routine 24-h Holter electrocardiogram at admission to stationary rehabilitation 3 weeks to 3 months after acute MI or CABG. Two groups did not differ except by age; CABG patients were younger (56 versus 64 years, P<0.01), but this did not influence differences in survival (NS). RESULTS: HRV was lower among CABG patients than among MI patients (SDNN=66 +/- 20 ms versus 77 +/- 14 ms; P<0.001), but cumulative survival and event-free survival were much better in the CABG group than in the MI group. During a 46 +/- 20 months follow-up, there were 10% new events in the CABG and 43% in the MI group (P<0.001). Mortality was 8% in the CABG and 33% in the MI group (log-rank=3.6; P<0.001). Unlike in the MI group, HRV was not different between survivors and non-survivors in the CABG group. CONCLUSIONS: In contrast to the strong prognostic potential of HRV in patients with MI, decreased HRV has no prognostic significance in patients who have undergone CABG surgery.     

Similar decline in post-myocardial infarction mortality among subjects with and without diabetes

BACKGROUND: Data from the 1970s and 1980s suggest that the rate of mortality from coronary disease for patients with diabetes has changed less than that for patients without diabetes. We evaluated trends in post-myocardial infarction mortality and morbidity in patients with and without diabetes over a 7-year period from 1990 through 1997, when substantial changes occurred in the management of coronary disease. METHODS: All patients discharged with the primary diagnosis of acute myocardial infarction (MI) from any Veterans Affairs Medical Center in the country between October 1990 and September 1997 were identified. Demographic, comorbid conditions, inpatient, outpatient, mortality, and readmission data were extracted. Mortality, trends in mortality over time, revascularization, readmissions, and length of hospital stay for MI were compared for the group with diabetes and the group without diabetes. Independent predictors of survival using a Cox regression model were examined. RESULTS: We identified 67,889 patients with MI, of whom 17,756 (26%) had diabetes. At 60 days post-MI, there was a 29% higher mortality rate in the group with diabetes (5.2% versus 4.0%, P < 0.001), which increased to 35% at 1 year (16.1% versus 11.9%, P < 0.001). Diabetes was independently associated with increased overall mortality. Age-adjusted 1-year post-MI mortality from 1991 to 1998 had a significant downward trend (4.9% decrease in odds of mortality per year, P < 0.001) regardless of diabetes status. CONCLUSIONS: Patients with diabetes showed a trend toward declining 1-year post-MI mortality rate that was not significantly different from that seen in patients without diabetes. Further work needs to be done to narrow the gap between the two groups.     

Impact of diabetes on mortality in patients with myocardial infarction and left ventricular dysfunction

BACKGROUND: Diabetes is a major risk factor for developing coronary heart disease. In patients with diabetes who survived myocardial infarction (MI), less is known about subsequent morbidity and mortality. We evaluated the effects of diabetes in post-MI patients with left ventricular dysfunction on cardiovascular events and death. METHODS: The Survival and Ventricular Enlargement, a randomized, double-blind, placebo-controlled multicenter trial, evaluated the efficacy of captopril vs placebo in 2231 patients following acute MI with left ventricular dysfunction defined as an ejection fraction less than or equal to 40%. Patients were randomly assigned to captopril or placebo 3 to 16 days following MI and were followed up for 2 to 5 years (mean, 3.5 years). RESULTS: Among the 2231, 496 (22.2%) were patients with a history of diabetes, of which 168 (33.9%) were treated with insulin. Patients with diabetes were significantly older; more likely to be women; have a history of prior MI or hypertension; be obese or manifest Killip class II or greater; and have higher systolic blood pressure, pulse pressure, and heart rate, as well as lower ejection fraction. During follow-up, 31.3% of patients with diabetes and 20.1% of nondiabetic patients died (P<.001). Furthermore, 50% of the patients with diabetes had at least 1 major cardiovascular event compared with 32.3% among the nondiabetic patients (P<.001). In multivariate analysis that adjusted for all significant differences in baseline characteristics, patients with diabetes had a 39% higher total mortality (P = .001) and 49% more cardiovascular events (P = .001). Among the patients with diabetes, baseline insulin treatment was associated with a greater risk of death (41.1% vs 26.2%; P = .001) and cardiovascular events (58.3% vs 45.7%; P = .008). CONCLUSIONS: In patients who survived MI with left ventricular dysfunction, diabetes increased risk of death from all causes even after controlling for differences in other risk factors. Patients with diabetes treated with insulin have a particularly higher mortality risk. Patients with diabetes who survived MI with left ventricular dysfunction, in particular those receiving insulin, are at high risk of subsequent mortality and cardiovascular events and thus require intensive risk factor modification, as well as evaluation for novel therapies.     

Timing of bypass surgery in stable patients after acute myocardial infarction

OBJECTIVES: To determine the optimal timing for bypass surgery in stable patients after acute myocardial infarction (MI). BACKGROUND: Coronary artery bypass graft surgery (CABG) is a proven treatment for coronary artery disease. Because of the hypothesized risk of hemorrhagic transformation, it had become common practice to wait four to six weeks after MI. Recently, improvements in surgical and perioperative management, as well as an increase in pre-CABG in-hospital waiting times and excess burden on health care resources, have pushed surgeons to operate earlier. The optimal timing for a stable patient to undergo CABG after MI is unclear, because there have been no randomized trials to answer this question. METHODS: The published literature comparing early versus late surgical revascularization procedures in stable post-MI patients was reviewed. RESULTS: No randomized, prospective trials were found; however, several retrospective studies were identified. Most series examining Q wave MIs showed that mortality is higher in the early stages post-MI and progressively decreases with time post-MI. When studies examined non-Q wave MIs separately, there appeared to be less of a mortality difference between early and late surgical revascularization. There was a large disparity between the definitions of early surgery post-MI among the studies, some as early as 6 h and others up to eight days. Factors that increased mortality include abnormal left ventricular function and urgency of surgery, and some studies found risk models helpful to define increased risk after infarction. The possible increased risk of early surgery may be balanced against the potential for improved remodelling, improved quality of life and decreased hospital stay costs. CONCLUSIONS: There is a need for a randomized, prospective trial examining the optimal timing for CABG in stable post-MI patients.     

Heart rate versus heart rate variability in risk prediction after myocardial infarction

INTRODUCTION: The aim of this study was to evaluate and compare heart rate and heart rate variability (HRV) in risk prediction after acute myocardial infarction (MI) and to evaluate the effect of beta-blocker treatment on the prognostic performance of heart rate and HRV. METHODS AND RESULTS: Three hundred sixty-six patients underwent 24-hour Holter recording 1 to 6 days after an MI. HRV was expressed as the standard deviation of all normal-to-normal intervals. Left ventricular systolic function was evaluated using the wall motion index. Half of the patients were taking a beta-blocker at the time of Holter recording. Mean follow-up was 44 months (median 34) after MI. By the end of follow-up, 82 patients had died. Mortality at 1 and 3 years was 12.5% and 22.6%, respectively. HRV, heart rate, wall motion index, number of ventricular premature beats per hour, and ventricular tachycardia were all significantly (P < 0.05) associated with mortality in univariate analysis, independent of beta-blocker therapy. In multivariate Cox analysis, only heart rate, wall motion index, number of ventricular premature beats per hour, and age had independent prognostic value (P < 0.001). In any model, including heart rate, HRV had no predictive value. CONCLUSION: The prognostic information of HRV is contained completely in heart rate, which carries prognostic information further than that of HRV. This result was independent of beta-blocker treatment.     

Osteopontin: Role in extracellular matrix deposition and myocardial remodeling post-MI

Remodeling after myocardial infarction (MI) associates with left ventricular (LV) dilation, decreased cardiac function and increased mortality. The dynamic synthesis and breakdown of extracellular matrix (ECM) proteins play a significant role in myocardial remodeling post-MI. Expression of osteopontin (OPN) increases in the heart post-MI. Evidence has been provided that lack of OPN induces LV dilation which associates with decreased collagen synthesis and deposition. Inhibition of matrix metalloproteinases, key players in ECM remodeling process post-MI, increased ECM deposition (fibrosis) and improved LV function in mice lacking OPN after MI. This review summarizes — 1) signaling pathways leading to increased expression of OPN in the heart; 2) the alterations in the structure and function of the heart post-MI in mice lacking OPN; and 3) mechanisms involved in OPN-mediated ECM remodeling post-MI.     

Risk assessment of post-myocardial infarction patients with preserved ejection fraction using 45-min short resting Holter electrocardiographic recordings

Background

Risk stratification for sudden cardiac death in post-myocardial infarction (post-MI) patients remains a challenging task. Several electrocardiographic noninvasive risk factors (NIRFs) have been associated with adverse outcomes and were used to refine risk assessment. This study aimed to evaluate the performance of NIRFs extracted from 45-min short resting Holter ECG recordings (SHR), in predicting ventricular tachycardia inducibility with programmed ventricular stimulation (PVS) in post-MI patients with preserved left ventricular ejection fraction (LVEF).

Methods

We studied 99 post-MI ischemia-free patients (mean age: 60.5 ± 9.5 years, 86.9% men) with LVEF ≥40%, at least 40 days after revascularization. All the patients underwent PVS and a high-resolution SHR. The following parameters were evaluated: mean heart rate, ventricular arrhythmias (premature ventricular complexes, couplets, tachycardias), QTc duration, heart rate variability (HRV), deceleration capacity, heart rate turbulence, late potentials, and T-wave alternans.

Results

PVS was positive in 24 patients (24.2%). HRV, assessed by the standard deviation of normal-to-normal R–R intervals (SDNN), was significantly decreased in the positive PVS group (42 ms vs. 51 ms, p = .039). SDNN values <50 ms were also associated with PVS inducibility (OR 3.081, p = .032 in univariate analysis, and 4.588, p = .013 in multivariate analysis). No significant differences were identified for the other NIRFs. The presence of diabetes, history of ST-elevation MI (STEMI) and LVEF <50% were also important predictors of positive PVS.

Conclusions

HRV assessed from SHR, combined with other noninvasive clinical and echocardiographic variables (diabetes, STEMI history, LVEF), can provide an initial, practical, and rapid screening tool for arrhythmic risk assessment in post-MI patients with preserved LVEF.     

Predictors and prognostic impact of recurrent myocardial infarction in patients with left ventricular dysfunction, heart failure, or both following a first myocardial infarction

IMS: Recurrent myocardial infarction (MI) is common after a first MI and is associated with increased morbidity and mortality. Predictors and prognosis of a recurrent MI with contemporary management are not well known. METHODS AND RESULTS: We assessed the predictors and prognostic impact of a first recurrent MI in 10,599 patients with left ventricular dysfunction, heart failure, or both following a first MI from the Valsartan in Acute Myocardial Infarction Trial (VALIANT) cohort. During a median follow-up of 27.4 months, 861 patients (9.6%) had a recurrent MI. The median time to recurrence was 136 days (quartiles 35-361 days), with a declining rate of recurrent MI within the first 3 months. The strongest predictors of recurrent MI were reduced estimated glomerular filtration rate, unstable angina, diabetes, and age. Mortality was markedly elevated (20.5%) within the first 7 days of a recurrent MI. Patients who survived 7 days after a recurrent MI continued to be at increased risk of death compared with patients without a recurrent MI and the risk of death remained elevated more than two-fold a year after the recurrent MI (adjusted hazards ratio 2.4, 95% confidence interval 1.7-3.2). One-year mortality for the entire VALIANT cohort was 10.3%, whereas 38.3% of the patients were dead 1 year after recurrent MI. Early reinfarctions (within 1 month) was associated with significantly higher 30-day mortality than later reinfarctions. CONCLUSION: Even in the context of contemporary treatment, a recurrent MI confers a significantly increased risk of death in patients following a high-risk first MI. Strategies aimed at reducing recurrent MI will thus likely prolong survival in post-MI survivors.     

Greater propensity of diabetic myocardium for oxidative stress after myocardial infarction is associated with the development of heart failure

Diabetic patients manifest an increased incidence of heart failure (HF) after myocardial infarction (MI), which presages an increase in morbidity and mortality. Although oxidative stress has been implicated in diabetic complications, oxidative stress status associated with comorbid conditions that frequently accompany diabetes remains unknown. Therefore, we examined antioxidants and oxidative stress in the surviving myocardium in relation to ventricular function during diabetic HF following MI. MI was produced in diabetic and nondiabetic rats by ligation of the left coronary artery. At 4 weeks post-MI, LV systolic pressure (LVSP), rate of pressure rise (+dP/dt), and rate of pressure decay (-dP/dt) were depressed to a significantly greater extent in diabetic compared to nondiabetic MI animals. Higher levels of myocardial 8-isoprostane (8-iso PGF(2alpha)), oxidized glutathione (GSSG), as well as greater upregulation of superoxide dismutase (SOD) and catalase (CAT) protein expression paralleled by increases in enzymatic activity was observed in the diabetic MI animals, indicating higher oxidative stress. These data demonstrate a greater derangement of oxidative stress in the surviving tissues of diabetic post-MI rat hearts concomitant with an increased functional severity of HF, and suggest that chronic antioxidant therapy may be useful for the prophylaxis of subsequent HF after MI associated with diabetes.     

Effect of exercise training on heart rate variability in patients with new-onset left ventricular dysfunction after myocardial infarction

BACKGROUND: Cardiac rehabilitation with exercise training alters sympathovagal control of heart rate variability (HRV) toward parasympathetic dominance in patients after acute myocardial infarction (MI). However, its effects on HRV in patients after MI with new-onset left ventricular dysfunction are yet unknown. We aimed to investigate the effects of 8 weeks of supervised, high-intensity exercise training on time- and frequency-domain measures of HRV in this selected patient population. METHODS AND RESULTS: Twenty-five men with an acute MI and a low ejection fraction were randomly assigned to enter or not to enter a training program in a regional rehabilitation center. HRV was evaluated before and after 1 and 2 months of training and at 12 months. Maximal exercise testing with respiratory gas exchange was performed at baseline and after training. Resting heart rate decreased (P <. 01) and the percentage of R-R intervals differing >50 ms from the preceding one (pNN50) increased (P <.05) after training. The standard deviation of R-R intervals (SDRR) tended to increase, but frequency-domain indexes remained unchanged. There was a significant decrease in SDRR (P <.05) and high-frequency power (P <.01) at 12 months in untrained patients. Exercise time increased by 38% and maximal oxygen uptake increased by 29% in the training group (P <. 01). CONCLUSIONS: Despite beneficial effects on clinical variables, exercise training did not markedly alter HRV indexes. A significant decrease in SDRR and high-frequency power in the control group suggests an ongoing process of sympathovagal imbalance in favor of sympathetic dominance in untrained patients after MI with new-onset left ventricular dysfunction.     

Calcineurin inhibition ameliorates structural, contractile, and electrophysiologic consequences of postinfarction remodeling

INTRODUCTION: After myocardial infarction (MI), the heart undergoes an adaptive remodeling process characterized by hypertrophy of the noninfarcted myocardium. Calcineurin, a Ca2+-calmodulin-regulated phosphatase, has been shown to participate in hypertrophic signal transduction. METHODS AND RESULTS: We investigated the effects of calcineurin inhibition by cyclosporin A on key structural, contractile, and electrophysiologic alterations of post-MI remodeling. Male Sprague-Dawley rats were divided into four groups: (1) sham-operated; (2) sham + cyclosporin A; (3) post-MI (left anterior descending coronary artery ligation); and (4) MI + cyclosporin A. Cyclosporin A (25 mg/kg/day) was initiated 2 days before surgery and continued for 30 days. Hypertrophy was evaluated by echocardiography and by changes in membrane capacitance of isolated myocytes from noninfarcted left ventricle (LV). The effects of cyclosporin A on hemodynamics and cardiac dimensions were investigated, and changes in diastolic function were correlated with changes in protein phosphatase 1 activity and the basal level of phosphorylated phospholamban. The effects of cyclosporin A on Kv4.2/Kv4.3 genes expression and transient outward K+ current (I(to)) density also were evaluated. One of 12 rats in the post-MI group and 2 of 12 rats in the post-MI + cyclosporin A group died within 48 hours after MI. There were no late deaths in either MI group. There was no evidence of heart failure (lung congestion and/or pleural effusion) in the two groups 4 weeks post-MI. Calcineurin phosphatase activity increased 1.9-fold in post-MI remodeled LV myocardium, and cyclosporin A administration resulted in an 86% decrease in activity. There were statistically significant decreases of LV end-diastolic pressure, LV end-diastolic diameter, and LV relative wall thickness in the post-MI + cyclosporin A group compared with the post-MI group. On the other hand, there was no significant difference in LV end-systolic diameter or peak rate of LV pressure increase between the two post-MI groups. Protein phosphatase 1 activity was elevated by 36% in the post-MI group compared with sham, and this correlated with a 79% decrease in basal level of p16-phospholamban. In the post-MI + cyclosporin A group, the increase in protein phosphatase 1 activity was much less (18% vs 36%; P < 0.05), and the decrease in basal level of p16-phospholamban was markedly ameliorated (20% vs 79%; P < 0.01). The decreases in mRNA levels of Kv4.2 and Kv4.3 and I(to) density in the LV of the post-MI + cyclosporin A group were significantly less compared with the post-MI group. CONCLUSION: Our results show that calcineurin inhibition by cyclosporin A partially ameliorated post-MI remodeled hypertrophy, diastolic dysfunction, decrease in basal level of phosphorylated phospholamban, down-regulation of key K+ genes expression, and decrease of K+ current, with no adverse effects on systolic function or mortality in the first 4 weeks after MI.     

Late potentials: are they related to cardiovascular complications in children with type 1 diabetes?

INTRODUCTION: The aim of our study was to assess the influence of cardiovascular complications on the occurrence of late ventricular potentials (LP) in children with diabetes mellitus type 1. MATERIALS AND METHODS: 72 children (36 boys and 36 girls), with average course of diabetes type 1 of 6.5+/-2.8 years, were included into the study. Standard physical examination, blood pressure measurements, signal-averaged electrocardiogram (SAECG), autonomic test, 24-h Holter monitoring, and Doppler echo investigations were performed. The control group consisted of 55 sex- and age-matched healthy children. We utilised nonlinear logistic regression analysis to assess the effect of disease duration, albuminuria, insulin demand, cardiac autonomic neuropathy (CAN), heart rate variability (HRV) indices, diabetes complication score, metabolic control, systolic and diastolic blood pressure, left ventricular parameters, and ventricular arrhythmias on LP occurrence. RESULTS: LP was discovered in 12 patients with diabetes and in 1 from the control group (P<.014). Diabetic children with LPs had thicker left ventricular posterior wall (LVPW) and longer diabetes duration time than children without LP (P<.045 and.031, respectively). Nonlinear regression model shows that duration of diabetes, CAN, and LVPW were the strongest independent parameters of LP occurrence (P<.001,.01 and.005, respectively). CONCLUSIONS: Diabetes type 1 is associated not only with increased occurrence of abnormal SAECG but also with LP presence. The disease duration, posterior wall thickness, and CAN are independent predictors of LP appearance in diabetes type 1 children. The presence of cardiovascular complication has no influence on LP occurrence in diabetic children.     

Relationship between left ventricular dysfunction and depression following myocardial infarction: data from the MIND-IT.

AIMS: Depression in patients following myocardial infarction (MI) is associated with an increased risk of mortality, but this association may be confounded by cardiac disease severity. We explored the relationship between left ventricular ejection fraction (LVEF) and depression in MI patients. METHODS AND RESULTS: In the Myocardial Infarction and Depression-Intervention Trial (MIND-IT), 1989 MI patients were assessed for depressive symptoms [Beck Depression Inventory (BDI) t = 0, 3, 6, 9, and 12 months post-MI]. Patients with BDI score > or =10 were assessed for the presence of International Classification of Diseases, 10th revision (ICD-10) depressive disorder (t = 3, 6, 9, and 12 months post-MI). Patients were divided into categories according to their LVEF during hospitalization, i.e. LVEF <30%, LVEF 30-45%, LVEF 45-60%, and LVEF > or = 60%. During hospitalization, presence of depressive symptoms was higher in patients with LV dysfunction. A relationship was found between LVEF and ICD-10 depressive disorder, i.e. a lower LVEF was associated with a higher rate of depression from 3-12 months post-MI (P < 0.01). Levels of LVEF inversely correlated with the BDI score at 3 months post-MI. Associations persisted after adjustment for demographics, risk factors for coronary artery disease, co-morbidity, Killip class, and baseline BDI score. CONCLUSION: In MI patients, the rate of depression and the severity of depressive symptoms are significantly related to the severity of LV dysfunction. The association between depression and LV dysfunction must be acknowledged when evaluating the prognostic effects of depression in cardiac patients.     

Comparison of various methods of assessment of heart rate variability including simple cardiovascular reflex tests as predictors of sudden cardiac death after myocardial infarction.

Long term heart rate variability is used for prediction of sudden cardiac death (SD). There are simpler methods of assessment of autonomic cardiac control - registration of heart rate response to reflex tests and determination of heart rate variability (HRV) on short ECG recordins. Comparative value for prognosis of SD after myocardial infarction (MI) of these 3 techniques has not been studied yet. METHODS: Valsalva maneuver with calculation of Valsalva ratio (VR) and deep breath test with calculation of difference between average maximal and minimal HR during first minute of test (HR difference - HRD) were performed in 188 patients on days 4-11 of MI (68.1% men, age 34-75 years, 93.6% on beta-blockers, without heart failure NYHA IV on the day of tests). Time and frequency domain HRV measures were assessed during 15 min at bed rest and at Holter monitoring for median 24 h on the same day as reflex tests. RESULTS: During follow up for 2.1+/-0.8 years there were 9 sudden and 13 non-sudden cardiac deaths. ROC analysis was used to determine cut-off values of VR, HRD and HRV measures for dichotomization of patients into those with low- and high-risk of SD and these values were used in logistic regression analysis. The following parameters were univariate predictors of SD: obtained at reflex tests - VR <1.13 (OR 7.8, 95% CI 1.6-39.0; p=0.012), HRD <3.36 (OR 4.3, 95% CI 1.1-16.9; p=0.034); HRV parameters from 15 min ECG recordings - total frequency power <739 ms(2), VLF power <294 ms(2), LF power <197 ms(2) and LF/HF <1.5; HRV parameters from long term ECG recording - LF power <491 ms(2), LF/HF <1.4. At multivariate analysis only LF power for 15 min <197 ms(2) among HRV parameters remained independent predictor of SD (OR 24.2, 95% CI 2.4-245.5; p=0.007). Other predictors were clinical - VF during acute phase of MI (OR 94.7, 95% CI 4.2-2115.2; p=0.004) and history of MI (OR 8.4, 95% CI 1.4-48.5; p=0.017). CONCLUSION: In this population of patients without severe heart failure low LF power on 15 min resting ECG recordings on days 4-11 of MI was more powerful predictor of sudden cardiac death during subsequent 2 years than other HRV parameters including heart rate response to Valsalva maneuver and deep breath test.     

冠心病合并糖尿病患者冠状动脉旁路移植术长期预后及危险因素的探讨

目的 探讨糖尿病及其合并症对冠状动脉旁路移植术长期预后的影响。方法 将226例连续行冠状动脉主路移植术的冠心病患者分为糖尿病组（116例）和非糖尿病组（110例），应用多变量分析方法分析两组患者术前及术后的临床特征，并随访术后总死亡率及心脏性死亡的发生率，探讨糖尿病组心脏性死亡的预测因素。结果 两组术前及术后的临床特征、既往心肌梗死病史及冠状动脉病变支数等差异无显著性。结果 两组术前及术后的临床特征、既往心肌梗死病史及冠状动脉病变支数等差异无显著性。平均随访3.5年总死亡率两组差异无显著性，但心脏性死亡的发生率糖尿病组明显高于非糖尿病组（15％与3％，P＜0.01）。糖尿病和术后低左室射血分数与心脏性死亡的发生率密切相关（95％可信区间1.29-15.20)。糖尿病组的心脏性主要是猝死、心力衰竭和心肌梗死。术后低左室射血分数、女性及糖尿病肾病是主要预测因素。结论 冠心病合并糖尿病患者冠状动脉旁路移植术长期预后不良，特别在低左室射血分数、女性及糖尿病肾病患者心脏性死亡的发生率高，预后差。应加强对糖尿病患者冠状动脉旁路移植术后心、肾功能障碍的治疗。