Early invasive versus ischaemia-guided strategies in the management of non-Q wave myocardial infarction patients with and without prior myocardial infarction; results of Veterans Affairs Non-Q Wave Infarction Strategies in Hospital (VANQWISH) trial.

AIMS: To compare the role of early invasive vs conservative management strategies in treating patients with non-Q wave myocardial infarction with or without a prior myocardial infarction. BACKGROUND: In patients recovering from non-Q wave myocardial infarction, the prognosis among patients with a first non-Q wave myocardial infarction is significantly better than in patients with a prior myocardial infarction, yet physicians often adopt an early invasive strategy to treat patients with a first non-Q wave myocardial infarction. METHODS: Non-Q wave myocardial infarction patients enrolled in the VANQWISH trial with a history of prior myocardial infarction were compared to those with a first non-Q wave myocardial infarction, for the trial primary end-point of death or myocardial infarction at 1 and 12 months, as well as for the initial randomized treatment strategy. RESULTS: Of the 920 non-Q wave myocardial infarction patients, 396 had a history of prior myocardial infarction and 524 did not. Patients with a history of prior myocardial infarction were older and had a higher incidence of multiple high-risk baseline characteristics than those with a first non-Q wave myocardial infarction. Compared to the group with a first myocardial infarction, the prior myocardial infarction group suffered more events at both 1 month (11% vs 6%, P=0.007) and at 12 months (29% vs 16%, P<0.001). This difference in outcome remained significant even after adjusting for confounding variables (P<0.0001 at 12 months). Among the non-Q wave myocardial infarction patients with a prior myocardial infarction, the frequency of death or recurrent myocardial infarction was similar in both invasive and conservative groups during the first year of follow-up. Among the first non-Q wave myocardial infarction group, those assigned to the conservative strategy had significantly fewer events (3% vs 9%, P=0.009 at 1 month; 12% vs 20%, P=0.016 at 12 months) and mortality (1% vs 5%, P=0.012 at one month; 5% vs 11%, P=0.009 at 12 months) than those assigned to early invasive strategy. CONCLUSION: A history of prior myocardial infarction identifies a moderately high-risk subset of non-Q wave myocardial infarction patients who display similar long-term outcomes regardless of the strategy assignment; however, patients with a first non-Q wave myocardial infarction may fare better with a conservative or ischaemia-guided approach during the first post infarction year.

Severe depression is associated with markedly reduced heart rate variability in patients with stable coronary heart disease.

OBJECTIVE: The purpose of this study was to investigate the relationship between depression and heart rate variability in cardiac patients. METHODS: Heart rate variability was measured during 24-hour ambulatory electrocardiographic (ECG) monitoring in 40 medically stable out-patients with documented coronary heart disease meeting current diagnostic criteria for major depression, and 32 nondepressed, but otherwise comparable, patients. Patients discontinued beta-blockers and antidepressant medications at the time of study. Depressed patients were classified as mildly (n = 21) or moderately-to-severely depressed (n = 19) on the basis of Beck Depression Inventory scores. RESULTS: There were no significant differences among the groups in age, gender, blood pressure, history of myocardial infarction, diabetes, or smoking. Heart rates were higher and nearly all indices of heart rate variability were significantly reduced in the moderately-to-severely versus the nondepressed group. Heart rates were also higher and mean values for heart rate variability lower in the mildly depressed group compared with the nondepressed group, but these differences did not attain statistical significance. CONCLUSION: The association of moderate to severe depression with reduced heart rate variability in patients with stable coronary heart disease may reflect altered cardiac autonomic modulation and may explain their increased risk for 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.

Morphology of right ventricular paced beats in posterior myocardial infarction.

Premature ventricular beats or paced beats can unmask new or old myocardial infarction when sinus beats fail to exhibit the typical infarct pattern. Knowledge of their morphology is vital, since they may be the earliest or even the only evidence of a myocardial infarction in certain cases. Morphology of premature ventricular beats or paced beats in anterior, anteroseptal, and inferior infarct has been described but not in the setting of a posterior infarct. We describe the morphology of right ventricular paced beats in a patient with posterior infarct and discuss its significance.

Assessment of ultra low frequency band power of heart rate variability: validation of alternative methods.

UNLABELLED: Alternative methods for assessing ULF spectral power using data from commercial Holter analysers were studied. Different heuristics for ULF calculation were compared with standard research software-based determination of ULF. SETTING: University Hospital. PATIENTS: 43 patients in NYHA classes I-IV heart failure and seven normals of similar ages. METHODS: SDNN, SDANN, ULF, VLF, LF, HF calculated from 24 h Holter monitoring using Oxford scanner software (method 1). ULF power also calculated by subtracting the sum of VLF. LF and HF powers obtained from the Holter scanner from the total variance (method 2) from 2 x ln(SDANN) (method 3), and by performing a standard, research-quality 24-h EFT analysis on the beat files (standard). Results of methods 1-3 were compared with standard using two-way ANOVA with repeated measures, regression analysis and a graphical technique. RESULTS: ULF calculated by method 1 correlated r=0.66 with standard but means differed substantially. In contrast, ULF calculated by method 2 correlated r=0.99 with standard with no significant differences between means. ULF calculated from SDANN (method 3) correlated r=0.983 with standard but means, while similar, were significantly lower (P=0.005). CONCLUSION: ULF reported by commercial HOLTER software is not equivalent to ULF power derived from 24 h FFT analysis. ULF calculated by method 2 can be considered equivalent to the ULF derived by standard 24-h FFT. ULF estimated by method 3 offers direct ULF power estimation from a temporal measure of HRV and can be useful when spectral values are not available.

Effect of exercise training on heart rate variability in healthy older adults.

OBJECTIVE: To determine the effect of exercise training on cardiac autonomic modulation in normal older adults by using analysis of heart rate variability. SUBJECTS: The exercise group consisted of 7 men and 9 women aged 66 +/- 4 years. The comparison group consisted of 7 men and 9 women also aged 66 +/- 4 years. METHOD: Heart rate variability was determined from 24-hour Holter recordings before and after 12 months of supervised exercise, which consisted of 3 months of stretching and 9 months of 5 hours/week aerobic exercise at approximately 70% of maximal oxygen uptake. Heart rate variability was measured at baseline and 12 months later in the comparison group, who had not changed their usual activity level. RESULTS: In the exercise group maximal oxygen consumption increased from 1.8 +/- 0.5 L/min to 2.2 +/- 0.7 L/min (P <.05). The standard deviation of normal interbeat intervals increased from 126 +/- 21 ms to 142 +/- 25 ms. Mean nighttime heart rate decreased from 67 +/- 6 beats/min to 63 +/- 5 beats/min. Increased fitness level had little effect on indexes of heart rate variability, which reflect parasympathetic or mixed sympathetic/parasympathetic modulation of heart rate. There was no change in heart rate or heart rate variability in the comparison group. CONCLUSIONS: Exercise training increases total heart rate variability in normal older adults. The most marked alterations are in nocturnal heart rate. Heart rate variability is stable over a 1-year period in older adults who do not alter their activity level.

Comparison based on age of baseline electrocardiographic abnormalities in non-Q-wave myocardial infarction. VANQWISH Trial Research Investigators. Veterans Affairs Non-Q-Wave Infarction Strategies In-Hospital.

OBJECTIVE: To compare the incidence of electrocardiographic abnormalities between older (age > or = 70 years) and younger patients presenting with acute non-Q-wave myocardial infarction. DESIGN: Retrospective review of qualifying electrocardiograms in 918 patients enrolled in the multicenter Veterans Affairs Non-Q-Wave Infarction Strategies In-Hospital (VANQWISH) study. SETTING: Seventeen Department of Veterans Affairs medical centers. PARTICIPANTS: A total of 918 patients (224 > or = 70 years old) with acute non-Q-wave myocardial infarction. MEASUREMENTS: Comparison of electrocardiograms in patients aged > or = 70 years and younger patients for presence of left ventriculary hypertrophy, widened QRS complex, ST and T wave abnormalities, rhythm other than sinus, heart rate > or = 80 beats/minute, and location of acute non-Q-wave myocardial infarction. RESULTS: Left ventricular hypertrophy and ST depression > or = 1 mm were significantly more frequent in older than in younger patients. CONCLUSIONS: Older patients presenting with non-Q-wave myocardial infarction have a greater incidence of left ventricular hypertrophy and ST depression on their electrocardiograms than younger patients. Both of these electrocardiographic findings have previously been associated with increased risk of death and recurrent myocardial infarction and may help account for the worse prognosis of non-Q-wave myocardial infarction in older patients.

Changes in 24-hour heart rate variability during normal pregnancy.

OBJECTIVE: We studied the effects of normal pregnancy on heart rate variability as a noninvasive index of maternal cardiovascular autonomic modulation. STUDY DESIGN: Twenty-four-hour Holter recordings were obtained for 8 healthy pregnant volunteers during early pregnancy (

Mechanisms of death in the CABG Patch trial: a randomized trial of implantable cardiac defibrillator prophylaxis in patients at high risk of death after coronary artery bypass graft surgery.

BACKGROUND: The CABG Patch trial compared prophylactic implantable cardiac-defibrillator (ICD) implantation with no antiarrhythmic therapy in coronary bypass surgery patients who had a left ventricular ejection fraction <0.36 and an abnormal signal-averaged ECG. There were 102 deaths among the 446 ICD group patients and 96 deaths among the 454 control group patients, a hazard ratio of 1.07 (P=0.63). The mechanisms of death were classified, and hypotheses were tested about the effects of ICD therapy on arrhythmic and nonarrhythmic cardiac deaths in the CABG Patch Trial and the Multicenter Automatic Defibrillator Implantation Trial (MADIT). METHODS AND RESULTS: The 198 deaths in the trial were reviewed by an independent Events Committee and classified by the method of Hinkle and Thaler. Only 54 deaths (27%) occurred out of hospital; 145 deaths (73%) were witnessed. Seventy-nine (82%) of the 96 deaths in the control group and 76 (75%) of the 102 deaths in the ICD group were due to cardiac causes. Cumulative arrhythmic mortality at 42 months was 6.9% in the control group and 4.0% in the ICD group (P=0. 057). Cumulative nonarrhythmic cardiac mortality at 42 months was 12. 4% in the control group and 13.0% in the ICD group (P=0.275). Death due to pump failure was significantly associated with death >1 hour from the onset of symptoms, dyspnea within 7 days of death, and overt heart failure within 7 days of death. CONCLUSIONS: In the CABG Patch Trial, ICD therapy reduced arrhythmic death 45% without significant effect on nonarrhythmic deaths. Because 71% of the deaths were nonarrhythmic, total mortality was not significantly reduced.

Insights from the study of heart rate variability.

Indices of heart rate variability (HRV) provide a window onto autonomic modulation of the heart. HRV indices, determined in either the time or frequency domain, are closely related and reflect parasympathetic, mixed sympathetic, and parasympathetic and circadian rhythms. In population studies, decreased HRV has had predictive value for mortality among healthy adults. It is a well-established risk factor for arrhythmic events and mortality among post-myocardial-infarction patients but has only moderate sensitivity and specificity. Decreased HRV has had mixed predictive success in congestive heart failure. Reduced HRV identifies diabetic patients with autonomic neuropathy. HRV in combination with other risk stratifiers, e.g. ejection fraction, can identify cardiac patients at especially high risk of mortality. Many but not all interventions associated with increased HRV are also associated with better survival rates.

RR interval dynamics before atrial fibrillation in patients after coronary artery bypass graft surgery.

BACKGROUND: Atrial fibrillation/flutter (AF) is a frequent complication of coronary artery bypass graft surgery (CABG) that leads to increased costs and morbidity. We hypothesized that heart rate variability (HRV), an indicator of cardiac sympathovagal balance, is altered before the onset of postoperative AF. Because nonlinear methods of HRV analysis provide information about heart rate dynamics not evident from usual HRV measures, we also hypothesized that approximate entropy (ApEn), a nonlinear measure of HRV, might have predictive value. METHODS AND RESULTS: Analysis of HRV was performed in 3 sequential 20-minute intervals preceding the onset of postoperative AF (24 episodes in 18 patients). These data were compared with corresponding intervals in 18 sex- and age-matched postoperative control subjects who did not develop AF. Patients had left ventricular ejection fractions >45% before surgery and were not receiving beta-blockers during ambulatory ECG monitoring after surgery. Logistic regression demonstrated that on the basis of averaged values for the three 20-minute intervals, increased heart rate and decreased ApEn were independently associated with AF. Heart rate dynamics before AF was associated with either lower (n= 19) or higher (n=5) RR interval variation by traditional measures of HRV or quantitative Poincaré analysis, suggesting the possibility of divergent autonomic conditions before AF onset. CONCLUSIONS: In the hour before AF after CABG surgery, higher heart rate and lower heart rate complexity compared with values in control patients were independent predictors of AF. Decreased ApEn occurs in patients with either increased or decreased HRV by traditional measures and may provide a useful tool for risk stratification or investigation of mechanisms.

Outcomes in patients with acute non-Q-wave myocardial infarction randomly assigned to an invasive as compared with a conservative management strategy. Veterans Affairs Non-Q-Wave Infarction Strategies in Hospital (VANQWISH) Trial Investigators.

BACKGROUND: Non-Q-wave myocardial infarction is usually managed according to an "invasive" strategy (i.e., one of routine coronary angiography followed by myocardial revascularization). METHODS: We randomly assigned 920 patients to either "invasive" management (462 patients) or "conservative" management, defined as medical therapy and noninvasive testing, with subsequent invasive management if indicated by the development of spontaneous or inducible ischemia (458 patients), within 72 hours of the onset of a non-Q-wave infarction. Death or nonfatal infarction made up the combined primary end point. RESULTS: During an average follow-up of 23 months, 152 events (80 deaths and 72 nonfatal infarctions) occurred in 138 patients who had been randomly assigned to the invasive strategy, and 139 events (59 deaths and 80 nonfatal infarctions) in 123 patients assigned to the conservative strategy (P=0.35). Patients assigned to the invasive strategy had worse clinical outcomes during the first year of follow-up. The number of patients with one of the components of the primary end point (death or nonfatal myocardial infarction) and the number who died were significantly higher in the invasive-strategy group at hospital discharge (36 vs. 15 patients, P=0.004, for the primary end point; 21 vs. 6, P=0.007, for death), at one month (48 vs. 26, P=0.012; 23 vs. 9, P=0.021), and at one year (111 vs. 85, P=0.05; 58 vs. 36, P= 0.025). Overall mortality during follow-up did not differ significantly between patients assigned to the conservative-strategy group and those assigned to the invasive-strategy group (hazard ratio, 0.72; 95 percent confidence interval, 0.51 to 1.01). CONCLUSIONS: Most patients with non-Q-wave myocardial infarction do not benefit from routine, early invasive management consisting of coronary angiography and revascularization. A conservative, ischemia-guided initial approach is both safe and effective.

Heart rate variability reflects severity of COPD in PiZ alpha1-antitrypsin deficiency.

BACKGROUND: Analysis of heart rate variability (HRV) is a powerful method of assessing severity of conditions affecting the autonomic nervous system. STUDY OBJECTIVE: To determine if HRV is decreased and if HRV reflects severity in COPD. DESIGN: Prospective determination of HRV from 24-h outpatient Holter recordings. PATIENTS: Eighteen individuals with PiZ alpha1-antitrypsin deficiency: 13 with COPD and 5 with normal FEV1. HRV was also determined in 18 matched normal control subjects. Approximately 3 years after the initial recording, all COPD subjects were contacted to determine current status. MEASUREMENTS: Indexes of heart rate (HR) and HRV were compared for groups of patients with and without COPD and their control subjects. RESULTS: Mean and minimum HRs were higher in COPD patients. Virtually all indexes of HRV were significantly decreased in COPD patients. No differences were found in HR or HRV between PiZ individuals with normal FEV1 and their age-and gender-matched control subjects. Patients who had a change in status (ie, death, lung transplant, listed for transplant) had significantly higher daytime HRs, lower values for HRV indexes reflecting mixed sympathetic and parasympathetic modulation of HR, and reduced daytime high-frequency spectral power, an index of cardiac vagal modulation. Significant correlations (r=0.48 to 0.88) were found between FEV1 and these and other indexes of HRV. Most other indexes of HRV also tended to be lower for the group whose status had changed. CONCLUSION: PiZ alpha1-antitrypsin deficiency COPD is associated with abnormal cardiac autonomic modulation. Indexes of HRV appear to reflect severity and may have prognostic value in COPD patients.

Design and baseline characteristics of the Veterans Affairs Non-Q-Wave Infarction Strategies In-Hospital (VANQWISH) trial. VANQWISH Trial Research Investigators.

OBJECTIVES: The Veterans Affairs Non-Q-Wave Infarction Strategies In-Hospital (VANQWISH) trial was designed to compare outcomes of patients with a non-Q wave myocardial infarction (NQMI) who were randomized prospectively to an early "invasive" strategy versus an early "conservative" strategy. The primary objective was to compare early and late outcomes between the two strategies using a combined trial end point (all-cause mortality or nonfatal infarction) during at least 1 year of follow-up. BACKGROUND: Because of the widely held view that survivors of NQMI are at high risk for subsequent cardiac events, management of these patients has become more aggressive during the last decade. There is a paucity of data from controlled trials to support such an approach, however. METHODS: Appropriate patients with a new NQMI were randomized to an early "invasive" strategy (routine coronary angiography followed by myocardial revascularization, if feasible) versus an early "conservative" strategy (noninvasive, predischarge stress testing with planar thallium scintigraphy and radionuclide ventriculography), where the use of coronary angiography and myocardial revascularization was guided by the development of ischemia (clinical course or results of noninvasive tests, or both). RESULTS: A total of 920 patients were randomized (mean follow-up 23 months, range 12 to 44). The mean patient age was 61 +/- 10 years; 97% were male; 38% had ST segment depression at study entry; 30% had an anterior NQMI; 54% were hypertensive; 26% had diabetes requiring insulin; 43% were current smokers; 43% had a previous acute myocardial infarction; and 45% had antecedent angina within 3 weeks of the index NQMI. CONCLUSIONS: Baseline characteristics were compatible with a moderate to high risk group of patients with an NQMI.

Differing effects of age on heart rate variability in men and women.

Gender and age are both known to affect heart rate variability (HRV). Their interaction is not known. HRV, determined from 24-hour Holter recordings, was compared between gender-matched older (15 men and 15 women, aged 67 +/- 3 years, range 64 to 76) and younger (15 men and 15 women, aged 33 +/- 4 years, range 26 to 42) subjects selected for an age difference of approximately 35 years. HRV for older and younger subjects was compared separately by gender. HRV was also compared by gender within groups. Heart rates were significantly higher, and all time and frequency domain indexes of HRV were significantly lower among the older than among the younger men. Among the women only the shorter term indexes of HRV were significantly lower in the older group. When HRV was compared by gender within age groups, there were no significant differences between men and women in the older group. In the younger group, men had lower heart rates, and all 24-hour time domain indexes of HRV, except those that reflect vagal modulation of heart rate, were significantly higher than those in women. We conclude that HRV is comparable in older men and women. However, HRV is differently affected by age. In men, for whom initial levels of HRV are significantly higher, older age is associated with a global reduction in HRV, reflecting reductions in both sympathetic and parasympathetic modulation and a loss of circadian variability. In women, older age is associated mainly with a decline in shorter term indexes of HRV without significant changes in circadian variability.

Heart rate variability is independent of age, gender, and race in congestive heart failure with a recent acute exacerbation.

Among normal adults, indexes of heart rate variability are affected by age, gender, and race. These effects are not seen among patients with congestive heart failure with a recent acute exacerbation, in whom indexes of heart rate variability are remarkably uniform and appear to be determined primarily by their recent cardiac failure.

Effect of 21 mg transdermal nicotine patches and smoking cessation on heart rate variability.

The effect of smoking cessation on cardiac autonomic tone, as reflected by indexes of heart rate variability (HRV), has not been reported. Current smokers (n = 54, mean +/- SD age 43 +/- 12 years) who desired to quit, and were smoking > or = 1 pack/day and had made > or = 1 prior attempt at quitting, had 24-hour electrocardiographic recordings. They then attended smoking cessation classes and used transdermal nicotine patches while abstaining from smoking. After 4 to 6 weeks of using 21 mg patches, the 24-hour electrocardiogram was repeated (n = 35). Four weeks after cessation of patch use, the 24-hour electrocardiogram was again recorded in subjects who continued to be abstinent (n = 25). Time and frequency domain measures of HRV based on normal R to R (NN) intervals were computed for all recordings. Smoking cessation significantly decreased heart rate, and increased all 24-hour time and frequency domain indexes of HRV. Part of this change occurred in the transition from smoking to the patch, and further changes occurred with cessation of patch use. For example, the standard deviation of average NN intervals was 114 +/- 28 ms at baseline, 121 +/- 41 ms with the patch, and 135 +/- 26 ms after quitting. At 4 weeks after cessation of all nicotine use, the average heart rate remained higher, and HRV remained lower than values reported for healthy, middle-aged adults.

Heart rate variability in a case of pheochromocytoma.

Indices of heart rate variability (HRV) reflect cardiac autonomic tone and may be markedly affected by pheochromocytoma. The effect of pheochromocytoma on HRV was determined by Holter monitoring before diagnosis, under pre-operative alpha-blockade and 5 and 19 months after surgery in a 40 year-old female. Mean heart rates, although higher under alpha-blockade, were unchanged by surgery but indices of HRV reflecting both short term (vagally mediated) and longer term (mediated by vagal, sympathetic and other influences) rhythms were diminished under alpha-blockade and post-surgery. High frequency power (0.15-0.40 Hz), an index of vagal tone, declined from 512 ms2 pre-diagnosis to 220 ms2 under alpha-blockade to just over 100 ms2 post-surgery. Low frequency power (0.04-0.15 Hz), a measure reflecting both vagal and sympathetic tone, declined from 409 ms2 pre-diagnosis to 186 ms2 under alpha-blockade and was just over 200 ms2 post-surgery. SDNN, the standard deviation of normal-to-normal interbeat intervals over 24 hours, declined from 118 ms pre-diagnosis to just over 70 ms both under alpha-blockade and post-surgery. The ratio of low frequency to high frequency power (LF/HF ratio) increased to 0.84 under alpha-blockade, and doubled after surgery (0.79; before, 2.05; after). These changes in HRV may provide insights into the effects of endogenous catecholamines and intrinsic counter-regulatory autonomic mechanisms on HRV.

Pulmonary artery aneurysm: review and case report.

Aneurysms involving the main pulmonary artery and its branches are rare. Clinical experience is limited and current knowledge is mainly derived from autopsy findings. This case report describes a patient with a pulmonary artery aneurysm associated with a previous, partially corrected stenotic pulmonary valve. The patient presented with symptoms suggestive of aneurysm dissection three decades after commissurotomy. The diagnostic approach and therapeutic intervention are emphasized with a review of the literature.