A non-invasive selective assessment of type I fibre mitochondrial function using 31P NMR spectroscopy. Evidence for impaired oxidative phosphorylation rate in skeletal muscle in patients with chronic heart failure.

BACKGROUND: Skeletal muscle abnormalities contribute considerably to the clinical expression of heart failure. Deconditioning, underperfusion and an increased number of type IIb glycolytical fibres lead to early lactate production and muscle fatigue at low exercise levels. Aerobic muscle metabolism may also be impaired, as suggested by biopsy studies. Thus far, no data are available from non-invasive studies to indicate the extent of aerobic muscle dysfunction during low-grade exercise which does not induce acidosis. METHODS AND RESULTS: Mitochondrial function of skeletal muscle during fibre type I activation was studied in 22 patients with chronic heart failure [NYHA class III, left ventricular ejection fraction 28 +/- 2%, (patients)] on ACE inhibitors, diuretics and digoxin, and in 20 normal subjects, using 31P NMR spectroscopy of a single right forearm flexor muscle during three mild intermittent exercise levels (0-40% of maximum voluntary contraction) and recovery time. At rest, the inorganic phosphate/phosphocreatine ratio was different [0.13 +/- 0.005 (patients) vs 0.09 +/- 0.002 (normal subjects), P = 0.0001]. However, intracellular pH was comparable. Local acidosis (tissue pH < 6.9) was avoided to prevent fibre type IIb activation. Calculated resting phosphate potential levels were comparable, but the slope and intercept of the linear relationship of phosphate potential and workload were significantly lower in patients than in normal subjects (11.7 +/- 0.7 vs 15.8 +/- 0.6 and 139 +/- 7 vs 196 +/- 7, patients vs normal subjects, indicating early exhaustion of intracellular energy at lower exercise levels. Also, maximum calculated workload at which tissue ADP stabilized was lower in patients than in normal subjects (88 +/- 7% vs 120 +/- 4% of maximum voluntary workload, patients vs normal subjects, P < 0.05). Time to recovery to pre-test phosphocreatine levels was prolonged by 46% in patients compared to normal subjects (P < 0.05). CONCLUSIONS: In heart failure, oxidative fibre mitochondrial function in skeletal muscle is impaired, as reflected by the reduced phosphate potential and oxidative phosphorylation rate, early exhaustion and slowed recovery of intracellular energy reserve at workloads, which do not affect intracellular pH.

Characteristics of conditioned and sedentary men with acute coronary syndromes.

To evaluate the role of habitual exertion in the development and manifestation of coronary artery disease, 36 well-conditioned men with acute coronary syndromes (4 with unstable angina, 23 with acute myocardial infarction and 9 survivors of sudden ischemic death) related to sports were compared with 36 sedentary men with the same syndromes occurring at rest. The mean age of the study subjects was 48 years (range 25 to 65). Patients exercised on average 6 hours/week (range 2 to 15) for > or = 10 years (range 10 to 45). Coronary angiography was performed within 4 hours after the onset of symptoms. The well-conditioned men had fewer risk factors than the inactive men (control subjects): fewer of them smoked (58 vs 94%, odds ratio 0.08) or had serum total cholesterol levels > or = 240 mg/dl (14 vs 56%, odds ratio 0.13, both p < 0.05). In addition, these men had less diseased (28 vs 72%, odds ratio 0.15, p < 0.02) and less severely stenotic (36 vs 78%, odds ratio 0.16, p < 0.03) coronary arteries. The association between activity levels and angiographic disease severity remained significant after correction for risk factors. Lesion morphology, site of the lesion and presence of thrombus of the culprit artery and diameter and dominance of all coronary arteries did not differ between the well-conditioned men and control subjects. This study suggests that regular strenuous exercise can reduce coronary artery disease and shows a common pathogenesis for acute coronary syndromes related and unrelated to sport.

Absence of beneficial effect of intravenous metoprolol given during angioplasty in patients with single-vessel coronary artery disease.

In a double-blind, randomized, placebo-controlled trial, the possible anti-ischemic effect of metoprolol during percutaneous transluminal coronary angioplasty was tested. Electrocardiograms, hemodynamics, and metabolism were studied in 27 patients with a stenosis in the left anterior descending coronary artery. Measurements took place before angioplasty, after each of four 1-minute occlusions and 15 minutes after the last balloon deflation. Patients were randomly given placebo or metoprolol (15 mg as a bolus intravenously, followed by an infusion of 0.04 mg/kg/hr). At the end of the procedure, the rate-pressure product had decreased by 15% (NS) and 23% (p = 0.001) in the placebo and metoprolol groups, respectively, mainly due to similar decreases in heart rate. Metoprolol tended to lower chest pain and reduce precordial ST-segment elevation due to angioplasty, but the effects were not statistically significant. Lactate, hypoxanthine, and urate release immediately after deflation was similar in both groups. Metoprolol reduced arterial plasma hypoxanthine throughout the procedure by about 30% (p < or = 0.02 vs. placebo). Thus, intravenous infusion of metoprolol did not significantly attenuate chest pain and ST-segment elevation, and failed to decrease cardiac lactate and oxypurine release. It did, however, reduce arterial hypoxanthine concentrations during angioplasty, possibly indicating that the beta-blocker inhibits extracardiac ATP catabolism.

Coronary angioplasty of bifurcational lesions without protection of large side branches.

To assess the risk and clinical relevance of side branch (SB) occlusion during angioplasty (PTCA) we attempted PTCA of major branches (MB) without protection of lesion-associated large (> or = 1.8 mm) SBs in 67 patients (50 men). There were 32 patients with unstable angina and 35 with stable angina. Their mean age was 55 years (range 31-77). There were 69 SBs: 43 with severe ostium stenosis (type A); 6 with severe non ostial stenosis (type B); and 20 with no or slight nonostial stenosis (type C). PTCA of the MB was successful in all but one patient who underwent acute bypass surgery. After MB PTCA occlusion occurred in 10 SBs (7A, 1B, 2C) and was asymptomatic in 5. Recanalization and dilatation was successful in 4 out of 5 symptomatic SB occlusions. A single patient developed a non-q wave myocardial infarction. PTCA was also attempted in 21 diseased SBs and failed in one. 21 SBs remained severely stenotic and 6 occluded. During follow-up symptomatic MB restenosis occurred in 12 patients, associated with restenosis in 4 out of 6 dilated SBs. Four patients underwent bypass surgery and 8 repeat successful PTCA. The SB was redilated in 2 cases and occluded silently in one. Angiography in 16 asymptomatic patients showed moderate MB restenosis in 3 and SB occlusion in 2. At 2.2 years follow-up 60 (89%) patients were asymptomatic with a normal exercise test and/or maintained angiographic result. Angioplasty of bifurcational lesions without SB protection can be effectively performed with a low rate of complications and a favourable long-term outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Recurrent acute myocardial infarction during sport.

A 48-yr-old well conditioned man developed acute myocardial infarction twice during sporting activities. After both events right coronary angiography showed a moderate proximal stenosis and, 5 months later, a subtotal obstruction at the site of prior slight lumen irregularity. This case suggests a causal relationship between sport and the occurrence of acute coronary events.

Quality of life perception during antihypertensive treatment: a comparative study of bisoprolol and enalapril.

The well-being of hypertensive patients may be adversely affected by the disease itself, its complications, and other concomitant processes such as anxiety, sedation, and side effects of prescribed drugs. Some recently developed antihypertensive agents have been suggested to be devoid of these deleterious effects on well-being expressed as quality of life. We compared the effect on quality of life of the angiotensin-converting enzyme (ACE) inhibitor enalapril to the effect of bisoprolol as a representative of a new class of selective beta 1-adrenoreceptor blocking agents. Fifty-seven patients with mild to moderate hypertension were eligible to enter an 18-week cross-over study, consisting of a single-blind 2-week run-in period and two 8-week double-blind cross-over periods. At the end of the run-in period and the two cross-over periods, both systolic and diastolic blood pressure (SBP, DBP) were assessed, as was quality of life perception by the Inventory of Subjective Health. During bisoprolol treatment, supine BP decreased from 163 +/- 2/102 +/- 1 to 144 +/- 3/86 +/- 1 mm Hg. The antihypertensive effect was at least as good with bisoprolol as with enalapril. Quality of life perception as measured with the Inventory of Subjective Health was comparable for the two drugs. Spontaneously mentioned adverse effects were more frequent (74%) during enalapril than during bisoprolol treatment. At the end of the study, 69% of patients chose to continue antihypertensive treatment with bisoprolol. Our results show that the highly selective beta 1-adrenoreceptor blocking drug bisoprolol is at least as effective as enalapril and has no deleterious effects on well-being.

Coronary angioplasty via saphenous vein grafts.

Percutaneous transluminal angioplasty of coronary stenoses distal to anastomosis of a venous graft was attempted through the graft 22 times in 19 patients. Ten patients had stable angina, seven unstable angina and two patients acute myocardial infarction. The mean interval between bypass surgery and angioplasty was 6.5 years (range 1-15). Fifteen lesions were dilated in the left anterior descending artery, five in the right coronary artery, and two in the circumflex artery. Three procedures were for double lesions. In two cases, a stenosed vein graft was also dilated. All grafts were cannulated with an El Gamal guiding catheter. The procedure failed in two cases. The remaining 20 lesions were successfully dilated. Early and late occlusion of the graft occurred in one patient, and coronary arterial stenosis recurred in two patients. All three patients underwent successful redilatation. The 17 patients undergoing successful dilatation were asymptomatic, with a normal exercise test and/or maintained angiographic result at follow-up of 14 months mean duration (range 2-48). Angioplasty of coronary stenosis through a vein graft is feasible, safe and effective. This therapeutic approach avoids the need for repeat bypass surgery and, as judged by long-term follow-up, has a favourable clinical outcome.

Clinical and angiographic observations on resuscitated victims of exercise-related sudden ischemic death.

The clinical and angiographic findings of 17 resuscitated victims of exercise-related sudden ischemic death are reported in an attempt to elucidate the mechanism(s) of these deaths. Ten survivors developed cardiac arrest during or after sporting activities (group A) and 7 others during or after an exercise stress test (group B). There were 15 men and 2 women. The mean age of group A was 46 years and of group B 55 years. Coronary risk factors, as well as previous angina and myocardial infarction, were more frequent in group B. Only 3 of the 17 survivors had anginal symptoms before sudden death. Sudden death in group A was associated with acute myocardial infarction in 8 and unstable angina in 2 and was associated in group B with acute myocardial infarction in 2, unstable angina in 3 and silent ischemia in 2. Coronary angiography was acutely performed in 15 patients. In most patients the ischemia-related coronary artery was totally or subtotally occluded. Clinical and angiographic findings indicate that exercise-related sudden ischemic death was due to an acute coronary event--in most cases unexpected and unpredictable. It is suggested that exercise-induced intracoronary changes were probably responsible for the development of acute coronary (sub)occlusion and sudden death.

Clinical characteristics and coronary angiographic findings of patients with unstable angina, acute myocardial infarction, and survivors of sudden ischemic death occurring during and after sport.

The clinical characteristics and coronary angiographic findings of 42 well-conditioned subjects with an acute ischemic event related to sport are reported. Five patients had unstable angina, 25 had acute myocardial infarction (AMI), and 12 were resuscitated victims of sudden ischemic death. Twenty-two events occurred during sport (group A) and 20 after sport (group B). There were two women and 40 men. The mean age was 46 years (range 25 to 65). Twelve out of 30 patients who smoked cigarettes had an adjunctive risk factor for coronary artery disease. Twelve others (28%) had no identifiable risk factor. Prodromal cardiac symptoms were detected in three patients (group A). Two patients had previous myocardial infarction (group B). Coronary angiography was performed acutely in 39 patients. The distribution of the ischemia-related coronary artery was comparable in both groups. The lesion morphology of 35 culprit coronary arteries was described as concentric in six patients and eccentric with regular borders (type I lesion) in 11 and irregular borders (type II lesion) in 18. Eccentric lesions consistent with ruptured plaques prevailed in both groups. Associated coronary artery disease was present in 10 patients. There was no relationship between the number of risk factors and the extent of diseased coronary arteries. Clinical characteristics and coronary angiographic findings of patients with unstable angina, AMI, and sudden death either during or after sport are similar and indicate a common pathogenesis. The probable mechanism of a coronary event related to sport is exercise-induced plaque rupture. In most instances such an event is unexpected and unpredictable. Identification of some subjects at risk is possible.

Value of immediate angioplasty after intravenous streptokinase in acute myocardial infarction.

To improve reperfusion, immediate percutaneous transluminal coronary angioplasty (PTCA) was considered after intravenous streptokinase (0.75 to 1.5 million U) was administered to 98 patients with acute myocardial infarction less than 4 hours after the onset of chest pain. Thirty-four culprit arteries were occluded (group A); 42 arteries were patent with residual stenosis of more than 70% (group B). Twenty-two patients had residual stenosis of less than 70% (group C); eight of these had severe disease of the remaining vessels. Group C patients were either treated conservatively or underwent bypass surgery. Immediate PTCA was attempted in 74 patients (32 in group A, 42 in group B) and was successful in 68 (92%). Emergency bypass surgery for acute occlusion after PTCA was required in two patients. Follow-up averaged 23 months (range, 16 to 47 months). Asymptomatic occlusion recurred in three patients. Restenosis occurred in five patients: four had early restenosis (one in group A, three in group B) and one had late restenosis (group B). These arteries were successfully redilated. Late reinfarction occurred in two patients. They were treated with intravenous urokinase and repeat PTCA. Elective bypass surgery was performed in three patients because of recurrent angina. They had severe three-vessel disease as revealed by control angiography. The mortality rate was 2.7% (two patients; one in group B had early reinfarction, and one patient in group A died suddenly after 17 months). Eighty-five percent of patients treated with PTCA alone remain free of symptoms. This approach has a high success rate and low morbidity and mortality rates. Long-term results are superior to thrombolysis alone.

Catheter reperfusion for failed emergency coronary angioplasty without subsequent bypass surgery.

A transluminal intracoronary reperfusion catheter was used in eight patients, seven with acute myocardial infarction and one with unstable angina after failed emergency coronary angioplasty. After placement of the reperfusion catheter across the occlusion, symptoms of ischemia resolved in each patient. Chest pain recurred 3 hr later in a single patient who underwent successful repeat angioplasty. The catheter was withdrawn within 6 hr after introduction. Control coronary angiography showed a patent vessel in all but one. Repeat angioplasty or bypass surgery was unnecessary. During 1 year mean follow-up time all patients remained free of symptoms. The reperfusion catheter is a safe and effective means of perfusing a coronary artery after failure of thrombolytic therapy and coronary angioplasty in cases where emergency bypass surgery is not performed because operative morbidity is expected to outweigh the benefit of myocardial salvage, or when it cannot be immediately organized.

Unstable angina, myocardial infarction and sudden death after an exercise stress test.

We performed coronary angiography within 95 minutes of the onset of symptoms in seven patients with an acute coronary event after an exercise stress test. The test was normal in six patients. Previous angiography in four patients revealed no evident or moderate obstructive coronary arterial disease. After the test, unstable angina developed in two patients, acute myocardial infarction in four and ventricular fibrillation in one, who was successfully resuscitated. At acute angiography the coronary artery involved was occluded in four and sub-totally obstructed in three. In three cases, coronary occlusion was due to thrombosis, vasospasm, or both. In six vessels there was an eccentric lesion, which is consistent with a ruptured plaque. These findings show that physical exercise can unexpectedly provoke an acute coronary event with sub-total or total occlusion of a previous angiographically normal or moderately obstructed coronary artery. The mechanism is probably related to exercise-induced plaque rupture which can produce coronary (sub)occlusion by coronary thrombosis, spasm, or both.

Myocardial infarction and sudden death after sport: acute coronary angiographic findings.

Thirteen patients, seven with acute myocardial infarction and six survivors of sudden death after sport, underwent coronary angiography within a mean of 104 min after the onset of symptoms. The admission electrocardiogram showed transmural myocardial ischemia in all patients. The ischemia-related vessel was occluded in all cases of sudden death and in three cases of acute myocardial infarction. Reperfusion was achieved in eight vessels: after intracoronary streptokinase in three, after intracoronary nitroglycerin in three, and mechanically in two. Coronary spasm was demonstrated in three vessels, and coronary thrombi, in four. The coronary lesion was described as either concentric in two or eccentric with irregular borders in eight. There was a high incidence of eccentric lesions consistent with ruptured plaques. The acute coronary angiographic findings of acute myocardial infarction and sudden death after sport are similar. Physical exercise can provoke myocardial infarction and sudden death probably by inducing plaque rupture that can evoke coronary spasm, thrombosis, or both.

Vasospastic coronary occlusion associated with a myocardial bridge.

A 53-year-old woman was admitted with unstable angina. Acute coronary angiography showed myocardial bridging and total occlusion of the left anterior descending artery in the middle one-third of its course. The occlusion was completely relieved by intracoronary administration of nitroglycerin. The occurrence of coronary spasm may explain angina and myocardial infarction in symptomatic patients with myocardial bridges.

Acute aortic regurgitation due to spontaneous rupture of a bicuspid aortic valve: detection by echocardiography.

A 42-year-old man was admitted with acute severe aortic regurgitation. There were no signs of a systemic infection. M-mode and two-dimensional echocardiography revealed bicuspid aortic valve and echocardiographic features consistent with aortic leaflet rupture. The diagnosis was confirmed at surgery. This report illustrates that spontaneous rupture of a bicuspid aortic valve should be considered in acute aortic regurgitation without infective endocarditis.

Exercise-induced plaque rupture producing myocardial infarction.

A 37-year-old man with unstable angina was subjected to coronary angiography. The right coronary artery showed a minor proximal stenosis, but there were no obstructive lesions in the left coronary artery. He developed a small inferior infarction. He was asymptomatic until re-admission 1 month later, 1 hour after a normal exercise test, with anterior myocardial infarction. Acute coronary angiography showed sub-total occlusion of the left anterior descending artery. The occlusion was partially relieved after intracoronary injection of nitroglycerin. Intracoronary infusion of streptokinase had no further effect. Balloon angioplasty was then successfully performed. It is suggested that stress-induced plaque rupture with intimal hemorrhage and secondary spasm resulted in sub-total occlusion of the left anterior descending artery producing the second myocardial infarction.