Characteristics of "malignant" vs. "benign" electrocardiographic patterns of early repolarization.

The electrocardiographic (ECG) pattern of early repolarization (ER) has historically been regarded as a benign ECG variant, but during the past few years, this concept has been challenged based on multiple reports linking the ER pattern with an increased risk of sudden cardiac death. Although the mechanistic basis of ventricular arrhythmogenesis in patients with ER pattern is still incompletely understood, there is increasing information about the ECG and phenotype characteristics of "malignant" vs. "benign" patterns of ER. This review presents the current evidence of markers of "benign" and a more severe nature of ER.

Polymorphisms of genes affecting thrombosis and risk of myocardial infarction.

BACKGROUND: As thrombosis is an essential factor in the pathogenesis of acute myocardial infarction (AMI), the genes of proteins affecting haemostasis are good candidate genes for AMI. DESIGN: Associations of the known polymorphisms of the coagulation factor VII (FVII) gene (R353Q), the coagulation factor XIII (FXIII) gene (V34L) and the glycoprotein Ia (Gp1a) gene (C807T) with the occurrence of AMI were studied in 142 AMI survivors and 142 age- and sex-matched control subjects. RESULTS: Among those who smoked, the L34 allele of the amino acid FXIII polymorphism was less common in the AMI patients (16%) than in the controls (27%) (P = 0.06), suggesting a possible interaction of AMI risk between the FXIII genotype and smoking status. No differences in the allele or genotype frequencies of the studied polymorphisms were seen between the whole study groups. Logistic regression analysis showed the carriers of the L34 allele of the FXIII amino acid polymorphism to have a significantly (P = 0.03) lower AMI risk compared with those homozygous for the V34 allele (odds ratio = 0.54, 95% confidence interval 0.31-0.93). CONCLUSION: The L34 allele of the amino acid polymorphism of the FXIII gene is associated with a decreased risk of AMI, and this protecting association seems to be more pronounced in smokers.

Qt dispersion and mortality in the elderly.

BACKGROUND: The prognostic value of QT interval dispersion measured from a standard 12-lead electrocardiogram (ECG) in the general population is not well established. The purpose of the present study was primarily to assess the value of QT interval dispersion obtained from 12-lead ECG in the prediction of total, cardiac, stroke, and cancer mortality in the elderly. METHODS: A random population sample of community-living elderly people (n = 330, age > or = 65 years, mean 74 +/- 6 years) underwent a comprehensive clinical evaluation, laboratory tests, and 12-lead ECG recordings. RESULTS: By the end of the 10-year follow-up, 180 subjects (55%) had died and 150 (45%) were still alive. Heart rate corrected QT (QTc) dispersion had been longer in those who had died than in the survivors (75 +/- 32 ms vs 63 +/- 35 ms, P = 0.01). After adjustment for age and sex in the Cox proportional hazards model, prolonged QTc dispersion (> or = 70 msec) predicted all-cause mortality (relative risk [RR] 1.38, 95% confidence interval [CI] 1.02-1.86) and particularly stroke mortality (RR 2.7, 95% CI 1.29-5.73), but not cardiac (RR 1.38, 95% CI 0.87-2.18) or cancer (RR 1.51, 95% CI 0.91-2.50) mortality. After adjustment for age, sex, body mass index, blood pressure, blood glucose and cholesterol concentrations, functional class, history of cerebrovascular disease, diabetes, smoking, previous myocardial infarction, angina pectoris, congestive heart failure, medication, left ventricular hypertrophy on ECG, presence of atrial fibrillation and R-R interval, increased QTc dispersion still predicted stroke mortality (RR 3.21, 95% CI 1.09-9.47), but not total mortality or mortality from other causes. The combination of increased QTc dispersion and left ventricular hypertrophy on ECG was a powerful independent predictor of stroke mortality in the present elderly population (RR 16.52, 95% CI 3.37-80.89). QTcmin (the shortest QTc interval among the 12 leads of ECG) independently predicted total mortality (RR 1.0082, 95% CI 1.0028-1.0136, P = 0.003), cardiac mortality (RR 1.0191, 95% CI 1.0102-1.0281, P < 0.0001) and cancer mortality (RR 1.0162, 95% CI 1.0049-1.0277, P = 0.005). CONCLUSIONS: Increased QTc dispersion yields independent information on the risk of dying from stroke among the elderly and its component, QTcmin, from the other causes of death.

Correlation properties and complexity of perioperative RR-interval dynamics in coronary artery bypass surgery patients.

BACKGROUND: Dynamic measures of heart rate variability (HRV) may uncover abnormalities that are not easily detectable with traditional time and frequency domain measures. The purpose of this study was to characterize changes in RR-interval dynamics in the immediate postoperative phase of coronary artery bypass graft (CABG) surgery using traditional and selected newer dynamic measures of HRV. METHODS: Continuous 24-h electrocardiograph recordings were performed in 40 elective CABG surgery patients up to 72 h postoperatively. In one half of the patients, Holter recordings were initiated 12-40 h before the surgery. Time and frequency domain measures of HRV were assessed. The dynamic measures included a quantitative and visual analysis of Poincaré plots, measurement of short- and intermediate-term fractal-like scaling exponents (alpha1 and alpha2), the slope (beta) of the power-law regression line of RR-interval dynamics, and approximate entropy. RESULTS: The SD of RR intervals (P < 0.001) and the ultra-low-, very-low-, low-, and high-frequency power (P < 0.01, P < 0.001, P < 0.001, P < 0.01, respectively) measures in the first postoperative 24 h decreased from the preoperative values. Analysis of Poincaré plots revealed increased randomness in beat-to-beat heart rate behavior demonstrated by an increase in the ratio between short-term and long-term HRV (P < 0.001) after CABG. Average scaling exponent alpha1 of the 3 postoperative days decreased significantly after CABG (from 1.22 +/- 0.15 to 0.85 +/- 0.20, P < 0.001), indicating increased randomness of short-term heart rate dynamics (i.e., loss of fractal-like heart rate dynamics). Reduced scaling exponent alpha1 of the first postoperative 24 h was the best HRV measure in differentiating between the patients that had normal ( 48 h, n = 7) intensive care unit stay (0.85 +/- 0.17 vs. 0.68 +/- 0.18; P < 0.05). In stepwise multivariate logistic regression analysis including typical clinical predictors, alpha1 was the most significant independent predictor (P < 0.05) of long intensive care unit stay. None of the preoperative HRV measures were able to predict prolonged intensive care unit stays. CONCLUSIONS: In the selected group of patients studied, a decrease in overall HRV was associated with altered nonlinear heart rate dynamics after CABG surgery. Current results suggest that a more random short-term heart rate behavior may be associated with a complicated clinical course. Analysis of fractal-like dynamics of heart rate may provide new perspectives in detecting abnormal cardiovascular function after CABG.

Impairment of heart rate variability during paclitaxel therapy.

BACKGROUND: Paclitaxel, which has been reported to be effective in treating metastatic breast carcinoma and advanced ovarian carcinoma, has been associated with cardiac side effects. Therefore, the effect of paclitaxel on cardiovascular autonomic regulation was studied. METHODS: Twenty-four-hour ambulatory electrocardiogram measurements were recorded twice from 14 women with breast or ovarian carcinoma: once before paclitaxel treatment and once on the day after the second chemotherapy course. Heart rate variability (HRV) was assessed with spectral analysis. For the frequency domain analysis, HRV was assessed in the very low (0.005-0.040 hertz [Hz]), low (0.040-0.150 Hz), and high frequency (0.150-0.400 Hz) spectral components. RESULTS: The ratio between low frequency and high frequency HRV decreased (daytime values of 2.7% [standard deviation (SD) 1.6] vs. 1.7% [SD 0.91; P = 0.0098) after 2 courses of paclitaxel. The circadian fluctuation of HRV also decreased in all studied frequency components. CONCLUSIONS: The observed changes in spectral characteristics suggest that autonomic modulation of the heart rate is impaired after paclitaxel therapy. However, from these data it is not clear whether the observed changes are permanent or whether autonomic cardiac function returns to normal some time after treatment. Further studies are needed to examine whether these indices based on HRV can be used to detect those patients at risk for cardiac side effects during chemotherapy.

Heart rate variability and progression of coronary atherosclerosis.

Low heart rate (HR) variability is associated with increased risk of cardiovascular morbidity and mortality, but the causes and mechanisms of this association are not well known. This prospective study was designed to test the hypothesis that reduced HR variability is related to progression of coronary atherosclerosis. Average HR and HR variability were analyzed in 12-hour ambulatory ECG recordings from 265 qualified patients participating in a multicenter study to evaluate the angiographic progression of coronary artery disease in patients with prior coronary artery bypass surgery and low high-density lipoprotein cholesterol concentrations (<1.1 mmol/L). Participants were randomized to receive a placebo or gemfibrozil therapy. The progression of coronary atherosclerosis was estimated by quantitative, computer-assisted analysis of coronary artery stenoses from the baseline angiograms and from repeated angiograms performed an average of 32 months later. The progression of focal coronary atherosclerosis of the patients randomized to placebo therapy was more marked in the tertile with the lowest standard deviation of all normal to normal R-R intervals (SDNN, 74+/-13 ms; mean decrease in the per-patient minimum luminal diameter -0.17 mm; 95% confidence interval [CI], -0.23 to -0.12 mm) than in the middle tertile (SDNN, 107+/-7 ms; mean decrease -0.05 mm; 95% CI, -0.08 to -0.01 mm) or highest tertile (SDNN, 145+/-25 ms; mean change 0.01 mm; 95% CI, -0. 04 to 0.02 mm) (P<0.001 between the tertiles). This association was abolished by gemfibrozil. SDNN was lower (P<0.001) and minimum HR was faster (P<0.01) in the patients with marked progression than in those with regression of focal coronary atherosclerosis. In multiple regression analysis including HR variability, minimum HR, demographic and clinical variables, smoking, blood pressure, glucose, lipid measurements and lipid-modifying therapy, progression of focal coronary atherosclerosis was independently predicted by the SDNN (beta=0.24; P=0.0001). Low HR variability analyzed from ambulatory ECG predicts rapid progression of coronary artery disease. HR variability provided information on progression of focal coronary atherosclerosis beyond that obtained by traditional risk markers of atherosclerosis.

Heart rate variability and occurrence of ventricular arrhythmias during balloon occlusion of a major coronary artery.

Experimental studies suggest that autonomic mechanisms are important in the genesis of ischemia-induced malignant ventricular arrhythmias, but the role of the autonomic nervous system in human arrhythmogenesis is not well known. To assess whether heart rate variability (HRV) predicts the occurrence of ventricular arrhythmias during acute coronary artery occlusion, we performed continuous electrocardiographic, heart rate, and blood pressure recordings before and during a 2-minute balloon occlusion of a stenotic coronary artery in 252 patients with no baseline ventricular premature complexes (VPCs). The ranges of nonspecific responses in heart rate and blood pressure were determined by analyzing a control group of 19 patients with no ischemia during a 2-minute balloon inflation in a totally occluded coronary artery. Balloon occlusion of a coronary artery was stopped because of complex, i.e., bigeminal or repetitive, VPCs in 14 patients, and solitary (<5) VPCs were observed in an additional 19 patients. During coronary occlusion, HRV increased (p <0.001) and heart rate decreased (p <0.05) in patients with no VPCs, whereas an opposite tendency to reduction in HRV (p = 0.08) was observed in patients with complex VPCs. Complex VPCs were observed in 5 (42%) of the 12 patients with a significant coronary occlusion-induced decrease in HRV, in 7 (3.5%) of 200 patients with no change in HRV, but in none of the 40 patients with a significant increase in HRV (p <0.001). Baseline HRV did not predict the occurrence of VPCs during coronary occlusion. Logistic regression analysis identified the decrease in HRV (p <0.001) to be the only independent predictor of complex VPCs. In conclusion, coronary occlusion-induced increase in HRV seems to protect against occurrence of complex ventricular arrhythmias during the early phase of abrupt coronary occlusion, suggesting that vagal activation may modify the outcome of acute coronary events in patients with coronary artery disease.

Power-law relationship of heart rate variability as a predictor of mortality in the elderly.

BACKGROUND: The prognostic role of heart rate (HR) variability analyzed from 24-hour ECG recordings in the general population is not well known. We studied whether analysis of 24-hour HR behavior is able to predict mortality in a random population of elderly subjects. METHODS AND RESULTS: A random sample of 347 subjects of > or =65 years of age (mean, 73+/-6 years) underwent a comprehensive clinical evaluation, laboratory tests, and 24-hour ECG recordings and were subsequently followed up for 10 years. Various spectral and nonspectral measures of HR variability were analyzed from the baseline 24-hour ECG recordings. Risk factors for all-cause, cardiac, cerebrovascular, cancer, and other causes of death were assessed. By the end of 10-year follow-up, 184 subjects (53%) had died and 163 (47%) were still alive. Seventy-four subjects (21%) had died of cardiac disease, 37 of cancer (11%), 25 of cerebrovascular disease (7%), and 48 (14%) of various other causes. Among all analyzed variables, a steep slope of the power-law regression line of HR variability (< -1.50) was the best univariate predictor of all-cause mortality (odds ratio, 7.9; 95% confidence interval [CI], 3.7 to 17.0; P<.0001). After adjusting for age and sex and including all univariate predictors of mortality in the proportional hazards analysis, ie, measures of HR variability, history of heart disease, functional class, smoking, medication, and blood cholesterol and glucose concentrations, all-cause mortality was predicted only by the slope of HR variability (adjusted relative risk, 1.74; 95% CI, 1.42 to 2.13; P<.0001) and a history of congestive heart failure (adjusted relative risk, 1.70; P=.0002). The slope of HR variability predicted both cardiac (adjusted relative risk, 2.05; P=.0002) and cerebrovascular death (adjusted relative risk, 2.84; P=.0001) but not cancer or other causes of death. CONCLUSIONS: Power-law relationship of 24-hour HR variability is a more powerful predictor of death than the traditional risk markers in elderly subjects. Altered long-term behavior of HR implies an increased risk of vascular causes of death rather than being a marker of any disease or frailty leading to death.

Antiarrhythmic effect of repeated coronary occlusion during balloon angioplasty.

OBJECTIVES: The purpose of the present study was to assess whether brief, repeated coronary artery occlusions during balloon angioplasty protect against ischemia-induced ventricular ectopy. BACKGROUND: Most sudden cardiac deaths are caused by fatal ventricular arrhythmias precipitated by early myocardial ischemia of acute coronary occlusion. In animals, a preceding 3- to 5-min coronary occlusion protects against malignant ventricular arrhythmias during a subsequent prolonged coronary occlusion. Whether such an antiarrhythmic effect caused by ischemic preconditioning occurs in humans is not known. METHODS: To assess the effects of a preceding, brief vessel occlusion-reperfusion cycle on the occurrence of ventricular ectopy, continuous electrocardiographic, heart rate and blood pressure recordings were performed in 156 patients before and during two identical balloon occlusions of a coronary artery (mean 111 s) separated by a 5-min equilibration period. RESULTS: The occluded vessel was the left anterior descending coronary artery in 94 patients, the left circumflex branch in 29 patients and the right coronary artery in 33 patients. Balloon occlusion of a coronary artery caused ventricular ectopy in 24 patients. The incidence of ventricular ectopy was higher during the first occlusion than during the second occlusion (21 patients [13.5%] vs. 11 patients [7%], p = 0.02). In 13 patients, ventricular ectopy was observed only during the first occlusion; in 8 patients during both occlusions; and in 3 patients only during the second occlusion. Bigeminal or repetitive ectopic beats were observed in eight patients during the first coronary occlusion and in four patients during the second occlusion. Atrial premature beats occurred during the first occlusion in three patients, but in none of the patients during the second occlusion. The 24 patients with ventricular ectopy during coronary occlusion had milder stenosis than the rest of the patients (mean [+/- SD] 74 +/- 12% vs. 81 +/- 12%, p = 0.01). The 13 patients with ventricular ectopy only during the first occlusion did not, however, differ significantly with respect to any clinical or angiographic features from the rest of the patients with ventricular ectopy. There were no significant differences in the signs of myocardial ischemia or hemodynamic variables between the sequential occlusions. CONCLUSIONS: A preceding, short vessel occlusion-reperfusion cycle seems to increase the electrical stability of ischemic myocardium.

Sex-related differences in autonomic modulation of heart rate in middle-aged subjects.

BACKGROUND: Women have worse outcomes when they experience acute myocardial infarction (MI), but the reasons for this sex-related difference are not well understood. Because cardiovascular neural regulation plays an important role in cardiac mortality, we studied possible sex-related differences in the autonomic modulation of heart rate (HR) in middle-aged subjects without known heart disease. METHODS AND RESULTS: Baroreflex sensitivity (BRS) and HR variability were studied in randomly selected, age-matched populations of middle-aged women (n = 186; mean age, 50 +/- 6 years) and men (n = 188; mean age, 50 +/- 6 years) without hypertension, diabetes, or clinical or echocardiographic evidence of heart disease. BRS measured from the overshoot phase of the Valsalva maneuver was significantly lower in women (8.0 +/- 4.6 ms/mm Hg, n = 152) than in men (10.5 +/- 4.6 ms/mm Hg, n = 151) (P < .001), and the low-frequency component of HR variability measured from ECG recordings also was lower in women (P < .001), whereas the high-frequency component was higher in women than in men (P < .001). The ratio between the low-and high-frequency oscillations also was lower in the women (P < .001). The increase of HR and decrease of high-frequency component of HR variability in response to an upright posture were smaller in magnitude in women than in men (P < .01 for both). After adjustment for differences in the baseline-variables, such as blood pressure, HR, smoking, alcohol consumption, and psychosocial score, the sex-related differences in BRS and HR variability still remained significant (P < .001 for all). Women with estrogen replacement therapy (n = 46) had significantly higher BRS and total HR variance than the age-matched women without hormone treatment (P < .01 for both), and the BRS and HR variability of the women with estrogen therapy did not differ from those of the age-matched men. CONCLUSIONS: Baroreflex responsiveness is attenuated in middle-aged women compared with men, but the tonic vagal modulation of HR is augmented. Hormone replacement therapy appears to have favorable effects on the cardiovascular autonomic regulation in postmenopausal women.

Significance of perfusion of the infarct related coronary artery for susceptibility to ventricular tachyarrhythmias in patients with previous myocardial infarction.

OBJECTIVE: To study the significance of perfusion of the infarct related coronary artery for susceptibility to ventricular tachyarrhythmias in patients with a remote myocardial infarction. SETTING: Tertiary referral cardiac centre. METHODS: Angiographic filling of the infarct related artery was assessed in a consecutive series of 85 patients with different susceptibilities to ventricular tachyarrhythmias after previous (> 3 months) Q wave myocardial infarction: 30 patients had a history of cardiac arrest (n = 16) or sustained ventricular tachycardia (n = 14), and sustained ventricular tachyarrhythmia was inducible in these by programmed electrical stimulation (arrhythmia group); 47 patients had no clinical arrhythmic events and no inducible ventricular tachyarrhythmias during programmed ventricular stimulation (control group). Eight patients without a history of any arrhythmic events were inducible into ventricular tachycardia. RESULTS: The patients in the arrhythmia group were older (63 (SD 8) years) than the control patients (59 (6) years, P < 0.05), and had larger left ventricular volumes in cineangiography (P < 0.01), but ejection fraction, severity of left ventricular wall motion abnormalities, previous thrombolytic therapy, and time from previous infarction did not differ between the groups. Patients with susceptibility to ventricular tachyarrhythmias more often had a totally occluded infarct related artery on angiography (77%) than patients without arrhythmia susceptibility (21%) (P < 0.001), and complete collateral filling of the infarct artery in cases without complete anterograde filling was less common in the arrhythmia group than in the control group (P < 0.001). Patients without a history of malignant arrhythmia but with inducible ventricular tachyarrhythmia also had no or poor perfusion of the infarct artery more often than the patients without inducible arrhythmia (P < 0.001). Logistic multiple regression showed that no or poor anterograde or collateral filling of the infarct related artery was the most powerful predictor of susceptibility to ventricular tachyarrhythmias (P < 0.001). Left ventricular size and function were not independently related to arrhythmic susceptibility. CONCLUSIONS: No or poor angiographic filling of the infarct related artery is closely associated with susceptibility to ventricular tachyarrhythmias late after acute myocardial infarction, suggesting that perfusion of the infarct artery will modify favourably the electrophysiological substrate of the infarct scar independently of the myocardial salvage achieved by early reperfusion.

Effects of perfusion of the infarct-related artery on risk markers of life-threatening arrhytmias in patients with prior myocardial infarction

Programmed electrical stimulation (PES), angiographic studies, Holter recording, 12-lead ECG and signal averaged ECG (SAECG, n=63) were performed in 109 consecutive patients with a prior Q-wave myocardial infarction (MI). Sixty-five patients (59 por cento) had TMI-class ) or 1 antegrade perfusion without significant collateral filling of the infarct related artery (IRA) (=poor persuion) and forty four (41 por cento) had either good antegrade or collateral perfusion of the IRA. The severity of corony artery disease or ejection fraction did not differ between the patients with poor or good perfusion of IRA. Heart rate variability and presence of late potentials on SAECG were also similar between the groups. but the dispersion of the QT interval was prolonged in the patients with poor perfusion of IRA (86 +/- 35 ms vs. 69 +/- 27 ms, p<0.01). The patients with poor perfusion of IRA had more often a clinical history of VT compared to those with good perfusion (68 por cento vs 9 por cento, p<0.01). Patets with good filling of the IRA after a prior MI have a low risk for VT, suggesting that preserved perfusion of the infarct scar stabilizes the electrophysiologic substrate.

Methotrexate-linked ventricular arrhythmias.

A 36-year-old male, who 1 year previously had survived a large anterior myocardial infarction, followed by cardiac arrest, was treated a few months for psoriasis with oral methotrexate, at single weekly oral doses of up to 10 mg, when he had to be hospitalized due to anginal pain and palpitation. Repeated 24-hour electrocardiogram recordings revealed ventricular ectopy up to 580 premature beats per hour. The ventricular premature beats were almost completely abolished after a few days' discontinuation of methotrexate therapy but recurred a few hours after an attempt to restart it had been made. A coronary angiogram showed only minimal wall abnormalities. Electrophysiological testing and endomyocardial biopsy were normal.

Asymptomatic coronary artery disease in diabetes: relation to common risk factors, lipoproteins, apoproteins and apo E polymorphism.

The risk factors for asymptomatic coronary artery disease (CAD) were examined in 138 diabetic patients. Following non-invasive screening examinations (exercise electrocardiography, dynamic thallium scintigraphy, 24-h electrocardiographic recording), CAD was confirmed angiographically in 21 symptom-free diabetic subjects with an ischaemic finding in at least one of the non-invasive tests. The prevalence of asymptomatic CAD in this cohort of diabetic patients was 21/132 (16%), which may be an underestimation because 6 patients refused angiography. Risk factors (age, diabetes, smoking, hypertension, serum lipoproteins, apoproteins and apo E phenotypes) were analysed according to the presence or absence of CAD. Multivariate logistic stepwise analysis did not show any definite changes of serum lipids, lipoproteins and apoproteins in type 1 (n = 72) and type 2 (n = 66) diabetic patients with or without asymptomatic CAD. The only factors associated with asymptomatic CAD were the duration of diabetes (P < 0.005) and the age of the patient (P < 0.05). These results suggest that in diabetic patients the major risk factor for premature coronary atherosclerosis is diabetes itself. Assessment of other risk factors does not seem to define any subgroup with asymptomatic CAD.

Changes in myocardial metabolism and transcardiac electrolytes during simulated ventricular tachycardia: effects of beta-adrenergic blockade.

Myocardial ischemia, electrolyte changes, and fluctuations in autonomic tone may play an important role in the presentation of malignant ventricular arrhythmias. beta-Adrenoceptor blocking agents have been shown to decrease the incidence of ventricular fibrillation and sudden cardiac death in patients with coronary artery disease. Therefore we investigated the changes in myocardial metabolism and transcardiac electrolytes during simulated ventricular tachycardia before and after beta-adrenergic blockade. Six patients with normal coronary arteries (group 1) and 12 patients with documented coronary artery disease (group 2) were included in the study. The right ventricle was paced with electrode catheters to a constant cycle length of 400 msec for 3 minutes. Blood samples were withdrawn simultaneously from the coronary sinus and femoral artery to determine the transcardiac differences in metabolic variables and electrolytes before the pacing, at the end of the pacing, and 2 minutes thereafter. After pacing, the patients were given intravenous propranolol (0.15 mg/kg), and the protocol was repeated. Intraarterial blood pressure and electrocardiogram were monitored continuously. There was a rapid decline of the mean arterial blood pressures after initiation of the pacing in both study groups, whereafter the pressures began to rise. Propranolol somewhat blunted the blood pressure recovery, especially in group 2. Norepinephrine levels increased during the pacing in both patient groups, and the increase was accentuated by beta-adrenergic blockade. The femoroarterial coronary sinus difference in lactate turned negative, and pH, PCO2 and potassium differences increased in group 2 during pacing. However, the myocardial energy state remained relatively good as estimated from the nonsignificant change in the transcardiac differences of the plasma adenosine catabolites. There were no changes in the metabolic variables or transcardiac electrolytes in group 1 patients during pacing. Propranolol did not prevent the metabolic ischemia, but it did prevent the pacing-induced decrease in coronary sinus potassium and increase in transcardiac potassium difference. Propranolol also decreased arterial levels of free fatty acids and their extraction in group 2 patients during pacing. In conclusion, blood pressure decay during simulated ventricular tachycardia is followed by instantaneous sympathoadrenergic activation. In patients with coronary artery disease, this process is accompanied by metabolic ischemia and net transfer of extracellular potassium into the intracellular space. The metabolic and electrolyte changes may result in alterations of electrophysiologic millieau, thereby also modifying the clinical characteristics of ventricular tachycardia. Propranolol decreases arterial levels of free fatty acids and prevents changes in transcardiac electrolytes observed in coronary artery disease patients during simulated ventricular tachycardia. These effects of propranolol may be of clinical significance.

Clinical and angiographic prediction of myocardial infarction and recurrence of severe angina during a five-year follow-up after coronary artery bypass grafting.

In a prospective, angiographically controlled study, 339 consecutive patients were examined to evaluate the pre-, peri- and postoperative risk factors for occurrence of myocardial infarction, and recurrence of severe angina during 5 years after coronary artery bypass grafting (CABG). The incidence of myocardial infarction was 6% and the recurrence of severe angina 13%. No pre- or perioperative variable could predict the occurrence of myocardial infarction. Postoperative ejection fraction was significantly lower in patients with than without myocardial infarction (58 +/- 10% vs 50 +/- 11%; p < 0.001), and the Cox proportional-hazards method showed a low postoperative ejection fraction to be the only significant risk factor for the occurrence of myocardial infarction (p = 0.02). Patients with a recurrence of severe angina had higher blood total cholesterol concentrations (7.7 +/- 1.4 vs 7.0 +/- 1.3 mmol/liter; p < 0.05) and triglyceride levels (2.7 mmol/l +/- 1.5 vs 2.0 +/- 1.0 mmol/liter; p < 0.01) than did those without angina, and also more often had > or = 1 occluded bypass graft 3 months after CABG (p < 0.05). No other pre- or postoperative variable could predict the recurrence of angina. Both total blood cholesterol concentration and triglyceride level were significant predictors of the risk of recurrent severe angina by the Cox proportional-hazards method (p = 0.01 and 0.03, respectively). Thus, reduced ejection fraction is a risk factor for subsequent myocardial infarction, whereas blood lipid abnormalities predict the recurrence of severe angina during the 5 years after CABG.(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy and safety of anticoagulant therapy started pre-operatively in preventing coronary vein graft occlusion.

Oral anticoagulant therapy with warfarin commenced pre-operatively (n = 102) to prevent coronary artery vein graft occlusions was compared in terms of efficacy and safety with dipyridamole and aspirin (n = 130) in a randomized consecutive series of patients. Anticoagulant therapy was started at least 2 weeks before coronary artery bypass surgery (CABG) and antiplatelet therapy was started at least 3 days before CABG with dipyridamole followed by a combination of 250 mg aspirin once a day via a nasogastric tube 6 h after CABG. Overall, vein graft patency at 3 months after surgery did not differ significantly between the anticoagulant group (203/275, 74%) and dipyridamole-aspirin group (238/311, 77%), but the occlusion rate for grafts with endarterectomy was higher in the anticoagulant (46%) than in the dipyridamole and aspirin group (16%), (P less than 0.05). The rate of peri-operative complications including deaths, re-operation and myocardial infarction was higher in the anticoagulant than antiplatelet group (26.5% vs 13.8%, P less than 0.05). The occurrence of postoperative bleeding complications did not differ significantly between the groups. Thus, oral anticoagulant therapy commenced pre-operatively has no advantages over conventional antiplatelet therapy in patients who undergo CABG. Neither antithrombotic regimens proved to be satisfactory for preventing acute bypass vein graft occlusions in this patient population with advanced coronary artery disease.

Usefulness of a postoperative exercise test for predicting cardiac events after coronary artery bypass grafting.

The predictive value of a postoperative exercise test in terms of cardiac events after coronary artery bypass grafting (CABG) was prospectively studied in 231 consecutive patients. During a 5-year follow-up there were 28 cardiac events (12%), of which 15 were cardiac deaths (13 sudden), and 13 were nonfatal myocardial infarctions. There was no difference in the rate of graft patency between groups with and without cardiac events, but ejection fraction was lower in patients with than without events (51 +/- 16% vs 58 +/- 10%; p less than 0.05). Duration of the exercise test was shorter, and maximal work load was lower in patients with cardiac events (p less than 0.05 for both). The prevalence of greater than or equal to 1 mm ST-segment depression was 22% (symptomatic in 25%, and silent in 75%) and did not differ between groups with and without cardiac events. After adjustment for prognostic variables using the proportional hazards method, diuretic treatment (p = 0.007) and a low postoperative ejection fraction (p = 0.04) remained significant for predicting the risk of cardiac events within 5 years of CABG, but exercise duration and work load did not have any significant predictive value. Thus, the predictive value of a postoperative exercise test is limited, and signs of impaired left ventricular function are of greater significance for the 5-year prognosis after CABG than are those of myocardial ischemia.

Clinical and angiographic prediction of cardiac death after coronary artery bypass graft surgery.

OBJECTIVES: To study the risk factors for cardiac mortality after coronary artery bypass graft surgery. DESIGN AND SETTING: Follow up study of patients who had undergone coronary artery bypass graft surgery at the University Hospital of Oulu, Finland. PATIENTS AND INTERVENTIONS: 339 consecutive patients who underwent cardiac catheterisation three months after bypass surgery. MAIN OUTCOME MEASURES: Incidence of cardiac deaths during the follow up period of five years and predictive value of clinical and angiographic variables for subsequent cardiac mortality. RESULTS: The incidence of cardiac deaths was 5.1%, and 81% of these were sudden deaths. The postoperative ejection fraction was significantly lower in the patients with subsequent cardiac death than in the survivors (p less than 0.001), and their left ventricular end systolic and end diastolic volumes were higher (p less than 0.001 and p less than 0.05 respectively). The incidence of cardiac deaths was 43% in the patients with a postoperative ejection fraction of less than 40%. The myocardial jeopardy index after surgery and the rate of graft patency were not significantly different in the survivors and patients who died. The only clinical factors that were different between the groups were postoperative use of diuretics (p less than 0.001) or digitalis (p = 0.02). After adjustment for other prognostic variables by the proportional hazards method, a low postoperative ejection fraction remained significant as a predictor of the relative risk of cardiac mortality five years after operation (p less than 0.01). CONCLUSIONS: Patients with angiographic evidence of impaired left ventricular function after bypass surgery are still at relatively high risk of dying suddenly, but myocardial ischaemia due to incomplete revascularisation is not strongly associated with an increased risk of cardiac mortality. Conventional clinical methods do not seem to be helpful for identifying patients with an increased risk of cardiac death after bypass surgery.

Prevalence and prognostic significance of exercise-induced ventricular arrhythmias after coronary artery bypass grafting.

Exercise-induced ventricular arrhythmias occur often after coronary artery bypass grafting (CABG), but their prognostic significance is unknown. Two hundred patients examined by exercise electrocardiography and cardiac catheterization (including left ventriculography, bypass graft and native coronary artery angiography) before and 3 months after CABG were prospectively followed up. Exercise-induced ventricular arrhythmias occurred more often after (49 of 200 patients, 24.5%) than before (32 of 200 patients, 16.0%) CABG (p less than 0.05). There were no differences between the patients with and without ventricular arrhythmias in the prevalence of graft patency (79 vs 80%) or the postoperative ejection fraction (57 +/- 9 vs 57 +/- 12%). Ten cardiac deaths occurred during the mean follow-up time of 61 +/- 19 months, 8 of which were witnessed sudden cardiac deaths. All cardiac deaths occurred in patients who did not have exercise-induced ventricular arrhythmias after CABG. The postoperative ejection fraction was lower in the cardiac death patients (42 +/- 16%) than in the survivors (58 +/- 10%) (p less than 0.01). No other clinical or angiographic variable predicted the occurrence of cardiac death. Thus, the prevalence of exercise-induced ventricular arrhythmias increases after CABG, but the occurrence of ventricular arrhythmias does not indicate an increased risk of cardiac death.