Muscle fiber characteristics in patients with peripheral arterial disease.

PURPOSE: There have been conflicting reports of muscle fiber type changes in patients with peripheral arterial disease (PAD). The purpose of this study was to examine the myosin heavy chain (MHC) expression as well as histochemical changes in the gastrocnemius muscle in patients with symptomatic PAD. METHODS: Needle biopsy specimens were obtained from the medial gastrocnemius of 14 subjects with PAD (mean age (+/- SD), 69.7 +/- 4.8 yr) and eight activity-matched control subjects (mean age, 65.1 +/- 6.6 yr). Ankle-brachial index was assessed using Doppler ultrasound to determine the hemodynamic status of the patients, and maximal walking performance was determined during a graded treadmill test. Expression of MHC isoforms was determined by SDS-PAGE. RESULTS: The proportion of MHC I was significantly smaller in PAD than in the controls (45.6 +/- 9.1% vs 58.8 +/- 15.0%). The proportion of MHC IIx was also larger in the subjects with PAD compared with the controls (22.9 +/- 9.1% vs 16.0 +/- 11.3%). In addition, there was a significant decrease in the cross-sectional area of the type I and type IIA fibers in the subjects with PAD as well as enhanced capillary density. CONCLUSIONS: This study showed a significant modification in the expression of MHC isoforms and muscle fiber type in the gastrocnemius in patients with symptomatic PAD. These results suggest that muscle ischemia resulting from PAD is an important factor in causing the adaptations in the contractile apparatus of the muscle.

Resistance training in patients with peripheral arterial disease: effects on myosin isoforms, fiber type distribution, and capillary supply to skeletal muscle.

The purpose of this study was to investigate the effects of a progressive resistance training program on myosin heavy chain isoform expression, fiber type, and capillarization in patients with symptomatic peripheral arterial disease. Patients were randomized to either a training group (n = 11, mean +/- SD, 70 +/- 6 years, 4 men, 7 women) or a control group (n = 9, 66 +/- 6 years, 5 men, 4 women). The training sessions were completed 3 times/week, using 2 sets of various exercises, each performed for 8-15 repetitions. Muscle biopsies were obtained before and after 24 weeks from the medial gastrocnemius. Following the 24-week training program, the training group had significantly decreased the percentage of myosin heavy chain type IIB. The proportion of type IIB/AB fibers as measured by using myosin adenosine triphosphatase histochemistry decreased significantly in the training group. There were significant increases in type I and type II fiber areas, and capillary density also increased significantly in the training group. There were significant increases in 10 repetition maximum leg press and calf press strengths in the trained subjects. There were no significant changes in any of the measurements in the control group. It is concluded that progressive resistance training results in significant increases in muscle strength and alters skeletal muscle composition of subjects with peripheral arterial disease.

Significance of prolonged left ventricular wall motion abnormalities after exercise echocardiography following non-Q-wave acute myocardial infarction.

Exercise echocardiography was used to assess myocardial ischemia after non-Q-wave acute myocardial infarction in 40 consecutive patients. Resting parasternal long- and short-axis views and apical 4- and 2-chamber views were recorded, digitized, and stored. A maximal symptom-limited exercise test was performed within 21 days (mean 17.7 +/- 3) using a cycle ergometer with continuous monitoring and the echocardiogram was repeated in the same views. Resting and exercise echocardiograms were then compared. Coronary angiography was performed in all patients within 21 days of exercise echocardiography. Stenosis in > or =50% of the lumen diameter was considered significant. Of the 40 patients studied, 29 (72%) had continuing angina and 11 (28%) had no angina. Eighteen patients (62%) with angina developed angina during exercise testing and 19 (65%) developed ST-segment depression. In patients without angina, 1 (9%) developed postexercise angina and 2 (18%) developed ST-segment depression. The mean wall motion score index after exercise increased from 1.2 +/- 0.3 to 1.8 +/- 0.4 in patients with continuing angina (p <0.001) and from 1.2 +/- 0.3 to 1.4 +/- 0.3 in patients without angina (p = NS). Prolonged wall motion abnormalities lasting >20 minutes persisted in > or =1 segment in 27 of 29 patients (93%) with angina or in 2 of 1 1 patients (18%) without angina (p <0.001). Patients with continued angina had predominantly 3-vessel coronary artery disease (22 of 29 [76%]) or 2-vessel disease (7 of 29 [24%]), and those without angina had 1-vessel disease (6 of 11 [55%]) or 2-vessel disease (4 of 11 [36%]). One patient had 3-vessel disease. The duration of wall motion abnormality demonstrated a significant relation to 2- and 3-vessel coronary artery disease (p <0.001). Thus, patients with non-Q-wave acute myocardial infarction had a high incidence of multivessel coronary disease not necessarily detected on routine exercise testing. There was also a significant incidence of prolonged wall motion abnormality.

Randomized controlled trial of prophylactic antiarrhythmic therapy in patients with inducible ventricular tachyarrhythmias after recent myocardial infarction.

Survivors of acute myocardial infarction who had inducible sustained ventricular tachyarrhythmias at programmed stimulation 1-4 weeks after infarction were recruited to a randomized pilot trial of Class I antiarrhythmic drugs, in an attempt to determine whether their mortality and risk of spontaneous ventricular tachycardia and fibrillation could be reduced by treatment. Of 136 eligible patients, 96 (71%) joined the trial and 47 were randomized to 'no treatment' and 49 were randomized to 'treatment' (quinidine, disopyramide or mexiletine given to attain 'therapeutic' serum levels). During follow-up, the two groups fared similarly. For the 'treatment' and 'no treatment' groups, the respective 3-year probabilities of remaining incident-free were:cardiac death, 0.91 vs 0.89; instantaneous death + non-fatal ventricular tachyarrhythmias, 0.87 vs 0.87; cardiac death + non-fatal ventricular tachyarrhythmias, 0.83 vs 0.85. The highest risk patients with inducible ventricular tachycardia fared similarly in the 'treatment' and 'no treatment' groups. The respective probabilities of remaining incident-free were: cardiac death, 0.89 vs 0.88; instantaneous death + non-fatal ventricular tachyarrhythmias, 0.79 vs 0.84; cardiac death + non-fatal ventricular tachyarrhythmias, 0.76 vs 0.77. We conclude that prophylactic Class I antiarrhythmic drug therapy with quinidine, disopyramide or mexiletine given to achieve a 'therapeutic' serum level does not appear to alter the prognosis of patients with inducible ventricular tachyarrhythmias after myocardial infarction.

Correlation between signal-averaged electrocardiogram and programmed stimulation in patients with and without spontaneous ventricular tachyarrhythmias.

This study examined the incidence of delayed ventricular activation on signal-averaged electrocardiograms and the incidence of inducible sustained ventricular tachycardia (VT) at programmed stimulation (1 or 2 extrastimuli) in patients with and patients without spontaneous ventricular tachyarrhythmias. The correlation between delayed ventricular activation and inducible VT was investigated in 371 patients with acute myocardial infarction (AMI). In 32 patients with no ventricular disease and no spontaneous arrhythmias (group I), ventricular activation time averaged 115 +/- 2 ms, compared with 166 +/- 3 ms (p less than 0.001) for 65 patients with spontaneous ventricular tachyarrhythmias late after AMI (group II). In AMI patients with no spontaneous arrhythmias, ventricular activation time averaged 133 +/- 2 ms for 306 patients studied 1 to 4 weeks after AMI (group III) and 130 +/- 2 ms for 67 patients studied 3 to 12 months after AMI (group IV). The values for group III and group IV patients were each significantly higher than for group I (p less than 0.001), but lower than that for group II (p less than 0.001). The incidence of delayed ventricular activation was 89% for group II, 26% for group III and 18% for group IV. Sustained VT was not inducible in group I patients, but was inducible in 78% of group II (p less than 0.001 vs group I) and 20% of group III (p less than 0.05 vs group I; p less than 0.001 vs group II) (group IV was not studied).(ABSTRACT TRUNCATED AT 250 WORDS)

Prognostic significance of ventricular tachycardia and fibrillation induced at programmed stimulation and delayed potentials detected on the signal-averaged electrocardiograms of survivors of acute myocardial infarction.

The relative prognostic significance of ventricular tachycardia and ventricular fibrillation inducible at programmed stimulation within 1 month of acute myocardial infarction was compared in a prospective study of 403 clinically well survivors of transmural infarction who were 65 years old or younger. The prognostic significance of delayed potentials on the signal-averaged electrocardiogram was also examined in a subset of 306 patients without bundle branch block. Among the study patients, 20% had inducible ventricular tachycardia, 14% had inducible ventricular fibrillation, and 66% had no inducible arrhythmias. The 2 year probability of remaining free from cardiac death or nonfatal ventricular tachycardia or fibrillation was 0.73 for those with inducible ventricular tachycardia, 0.93 for those with inducible ventricular fibrillation, and 0.92 for those with no inducible arrhythmias. The cycle length of inducible ventricular tachycardia was 230 msec or more in 70% of the patients with inducible tachycardia who died. Of the patients studied by signal-averaged electrocardiography, 26% had delayed potentials. At 2 years, the probability of remaining free from cardiac death or nonfatal ventricular tachycardia or fibrillation was 0.73 for patients with delayed potentials and 0.95 for patients with no delayed potentials. There was a significant correlation (p less than .001) between the presence of delayed potentials and the ability to induce ventricular tachycardia. In conclusion, in survivors of recent infarction who have not had spontaneous ventricular tachycardia or fibrillation, inducible tachycardia (but not inducible fibrillation) at programmed stimulation predicts a significant risk of death or spontaneous tachycardia or fibrillation. A similar risk is found for patients with delayed potentials on the signal-averaged electrocardiogram.

Effect of antiarrhythmic therapy on delayed potentials detected by the signal-averaged electrocardiogram in patients with ventricular tachycardia after acute myocardial infarction.

The ability of class I and class II antiarrhythmic drugs to either abolish delayed potentials or modify their timing was investigated in 39 patients with spontaneous ventricular tachycardia (VT) after myocardial infarction. Before the study all patients had delayed potentials on the signal-averaged electrocardiogram and inducible VT with programmed stimulation. These investigations were repeated during 67 trials of oral antiarrhythmic therapy (mexiletine 25, quinidine 24, metoprolol 13, disopyramide 2, procainamide 1, drug combinations 2). Delayed potentials were abolished in only 5 trails (7%), which was within the baseline variability of 8.5% for detection of delayed potentials. In the 7 trials in which VT inducibility was suppressed, delayed potentials persisted in 6 and mean ventricular activation time was virtually unchanged (151 ms before drug therapy, 152 ms after). Quinidine, mexiletine and metoprolol caused no consistent change in ventricular activation time. There was also no change in mean ventricular activation time (164 ms before and 163 ms after drug treatment) in patients in whom spontaneous VT did not recur with drug therapy during follow-up. Thus, the tested antiarrhythmic drugs had no consistent effects on presence or timing of delayed potentials on the signal-averaged electrocardiogram, even when VT inducibility was suppressed or recurrence of spontaneous VT was prevented.

Value of programmed stimulation and exercise testing in predicting one-year mortality after acute myocardial infarction.

The ability of programmed ventricular stimulation and exercise testing to predict 1-year mortality after acute myocardial infarction (AMI) was investigated in 228 clinically well survivors of AMI. Patients with inducible ventricular tachycardia (VT) or ventricular fibrillation (VF) had a higher mortality rate than those without inducible arrhythmias (26% vs 6%, p less than 0.001). Exercise-induced ST-segment change of 2 mm or more was associated with a higher mortality rate than ST change of less than 2 mm (11% vs 4%, 0.05 less p less than 0.10). Of patients who had both tests, 62% had no inducible ventricular tachycardia or ventricular fibrillation and ST change of less than 2 mm, and only 1% died during the first year. Thus, in clinically well survivors of AMI, programmed stimulation is a powerful predictor of first-year mortality; programmed stimulation and exercise testing together predict virtually all deaths within the first year, and they can identify a large group of patients with a very low mortality rate.

A new protocol of programmed stimulation for assessment of predisposition to spontaneous ventricular arrhythmias.

We have devised a simple method for identifying predisposition to spontaneous sustained ventricular fibrillation (VF) and tachycardia (VT). A standardized protocol of programmed stimulation was applied to 111 control subjects without ventricular disease and with no history of VF or VT (Group I) and to 27 patients with previous myocardial infarction and documented spontaneous (in the absence of evidence of further acute myocardial ischaemia) VF or VT (Group II). The stimulation protocol consisted of single and paired ventricular extra stimuli introduced during ventricular drive at the right ventricular apex and outflow tract, at twice diastolic threshold current intensity and at 20 mA. None of the Group I subjects exhibited VF or sustained (more than 10 s) VT. In contrast sustained arrhythmias were induced in 24 (89%) of Group II patients. We conclude: In our study population, initiation of a sustained ventricular tachyarrhythmia at programmed stimulation was both a sensitive (89%) and specific (100%) indicator for predisposition to spontaneous VF and VT.

Ventricular electrical instability: a predictor of death after myocardial infarction.

The results of a prospective study of ventricular electrical instability after myocardial infarction (MI) are presented. Ventricular electrical stability was assessed using a standardized protocol of programmed stimulation in 165 hemodynamically stable patients 6 to 28 days after acute MI. Ventricular electrical instability was defined as induction at programmed stimulation of ventricular fibrillation (VF) or ventricular tachycardia (VT) lasting at least 10 seconds. Of 165 MI survivors, 38 (23%) had ventricular electrical instability. No significant differences were noted between stable and unstable patients in terms of coronary prognostic index, elevation of serum creatine phosphokinase, coronary anatomy, site of MI, or frequency of VT within 48 hours of MI. The mean follow-up period was 8 months (range 0 to 12). There were 7 deaths in stable patients (5 from cardiogenic shock, 1 from septicemia, and 1 unwitnessed) and 10 deaths in unstable patients (8 instantaneous, 1 from cardiogenic shock, and 1 unwitnessed) during the subsequent year. In addition, 2 of 127 stable patients and 4 of 38 unstable patients had spontaneous VT from which they were satisfactorily resuscitated. Thus, the sensitivity of ventricular electrical instability as a predictor of instantaneous death or spontaneous VT was 86% and the specificity 83%. The predictive accuracy of the absence of ventricular electrical instability as an indicator for the absence of instantaneous death or spontaneous VT was 98%. The predictive accuracy of the presence of ventricular electrical instability as a predictor of instantaneous death or spontaneous VT was 32%. Thus, patients with ventricular electrical instability after MI have a high risk of instantaneous death within 1 year; patients without ventricular electrical instability after MI have a low risk of instantaneous death within 1 year; prospective studies of antiarrhythmic therapy and measures to prevent reinfarction and optimize left ventricular performance are required to determine whether instantaneous death can be prevented in unstable patients; and therapy to prevent reinfarction and optimize left ventricular performance may offer the best chance to improve prognosis in stable patients.