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Query: UMLS:C0038454 (stroke)
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A multicentre, randomised, open trial with a 2 x 2 factorial design was conducted to compare the benefits and risks of two thrombolytic agents, streptokinase (SK, 1.5 MU infused intravenously over 30-60 min) and alteplase (tPA, 100 mg infused intravenously over 3 h) in patients with acute myocardial infarction admitted to coronary care units within 6 h from onset of symptoms. The patients were also randomised to receive heparin (12,500 U subcutaneously twice daily until discharge from hospital, starting 12 h after beginning the tPA or SK infusion) or usual therapy. All patients without specific contraindications were given atenolol (5-10 mg iv) and aspirin (300-325 mg a day). The end-point of the study was the combined estimate of death plus severe left ventricular damage. 12,490 patients were randomised to four treatment groups (SK alone, SK plus heparin, tPA alone, tPA plus heparin). No specific differences between the two thrombolytic agents were detected as regards the combined end-point (tPA 23.1%; SK 22.5%; relative risk 1.04, 95% Cl 0.95-1.13), nor after the addition of heparin to the aspirin treatment (hep 22.7%, no hep 22.9%; RR 0.99, 95% Cl 0.91-1.08). The outcome of patients allocated to the four treatment groups was similar with respect to baseline risk factors such as age, Killip class, hours from onset of symptoms, and site and type of infarct. The rates of major in-hospital cardiac complications (reinfarction, post-infarction angina) were also similar. The incidence of major bleeds was significantly higher in SK and heparin treated patients (respectively, tPA 0.5%, SK 1.0%, RR 0.57, 95% Cl 0.38-0.85; hep 1.0%, no hep 0.6%, RR 1.64, 95% Cl 1.09-2.45), whereas the overall incidence of stroke was similar in all groups. SK and tPA appear equally effective and safe for use in routine conditions of care, in all infarct patients who have no contraindications, with or without post-thrombolytic heparin treatment. The 8.8% hospital mortality of the study population (compared with approximately 13% in the control cohort of the GISSI-1 trial) indicates the beneficial impact of the proven acute treatments for AMI.
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PMID:GISSI-2: a factorial randomised trial of alteplase versus streptokinase and heparin versus no heparin among 12,490 patients with acute myocardial infarction. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico. 197 87

Patients surviving acute myocardial infarction (AMI) may experience several clinical events (reinfarction, congestive heart failure, sudden death) still responsible for high mortality rates. AMI early complicated by residual angina, left ventricular dysfunction, or malignant arrhythmias has a worse prognosis. Secondary prevention of myocardial infarction and death has been the end point of many clinical trials in the past two decades. It is well known that beta blockers prevent sudden death if administered chronically after AMI. Meta-analysis of controlled randomized trials demonstrated a significant reduction in reinfarction and vascular death with long-term antiplatelet treatment. Oral anticoagulants prevent fatal and non-fatal reinfarction and show a trend towards lower mortality rates, though treated patients have a higher incidence of haemorrhagic events, particularly stroke. Early administration of heparin gave contradictory results on short-term prevention of myocardial infarction and death after AMI. Data on long-term heparin therapy point out a significant reduction in recurrent AMI and a trend towards a decrease in general mortality.
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PMID:Heparin and secondary prevention of acute myocardial infarction. 198 6

Extended ambulatory electrocardiographic monitoring in the patient's customary environment provides clear evidence of circadian patterns in myocardial ischemic episodes. In patients with effort angina, the highest activity occurs between 6 AM and noon. This coincides with peaks in diurnal variation of frequency of acute myocardial infarction, stroke, and sudden death. A number of potential underlying common triggering mechanisms, including catecholamine secretion, sympathetic nervous system activity, blood pressure, heart rate, cortisol secretion, and aggregability of platelets, exhibit similar surges. As a result of these coinciding morning peaks, myocardial oxygen demand is increased and oxygen supply reduced after a person arises in the morning. Attention to this vulnerable period is merited in the timing and choice of medication, both to prevent or reduce ischemia and to modify potential disease-triggering mechanisms.
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PMID:Circadian variations in myocardial ischemia. Implications for management. 198 40

In asymptomatic patients the importance of silent ischemic ST-T wave changes on Holter monitoring is known to be a significant predictive variable for one-year mortality of postmyocardial infarction patients. This case report represents the uses of ambulatory ECG to detect ischemic ST changes in patients who have had recent strokes. The cases reported here of silent myocardiac ischemia in stroke patients reflect previous reports in which 70% of the ischemic episodes in patients with symptomatic coronary artery disease are not associated with angina and in which approximately 10% to 15% of acute myocardial infarctions are silent. We now believe that the incidence of "silent" ischemia may be precipitated in poststroke patients during their rehabilitation program. This belief is supported by two main factors. First, a high level of personally relevant mental stress exists which activates the sympathoadrenal system, which may lead to myocardial ischemia. Second, some stroke patients become aphasic and are unable to communicate adequately even if they experience angina symptoms. We have found that poststroke, most patients could not undergo exercise treadmill testing secondary to a variety of factors: inability to coordinate limbs, poor endurance, inability to follow directions, and/or lack of attention. We now propose that 24-hour monitoring for ST-T wave changes poststroke should be considered as part of a vigorous investigation for myocardial ischemia during the rehabilitation of these patients because they have an increased risk of cardiac morbidity.
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PMID:Silent myocardial ischemia during rehabilitation for cerebrovascular disease. 198 25

We have performed coronary bypass grafting in 25 patients 80 years of age or more. The patients' preoperative conditions were characterized by recent myocardial infarction (16/25, or 64%), obesity (15/25, or 60%), hypertension (14/25, or 56%), and left ventricular dysfunction (21/25, or 84%). There were no deaths in the hospital or within 30 days of operation (0/25, or 0%). Postoperative complications occurred in five cases (20%). Complications were leg incision infection (2/25, or 8%), urinary tract infection (1/25, or 4%), stroke (1/25, or 4%), and transient neurologic deficit (1/25, or 4%). There were no instances of reoperation for bleeding, perioperative myocardial infarction, renal failure, pulmonary failure, intraaortic balloon pump use, or sternotomy infection in these patients. Eleven patients (44%) were hospitalized for fewer than 10 days after operation, and all but two (23/25, or 92%) were discharged within 20 days after operation. All patients were followed up, and survival and New York Heart Association functional class were determined. Cumulative survival rate was 94% at 1 year and 88% at 5 years. The cumulative percent survival rate with class I or II function was 92% at 1 year and 80% at 5 years. No patient had recurrent angina.
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PMID:Coronary artery bypass grafting in the octogenarian. 202 43

Between 1968 and 1975, 1698 patients underwent coronary artery bypass with autogenous saphenous vein and were followed for up to 20 years. Age at operation was 53.9 +/- 8.4 years, and 1485 were men (88%). Angina was present in 1637 patients (96%). There was single-vessel disease in 306 patients (18%), double-vessel in 642 (38%), triple-vessel in 550 patients (32%) and left main stenosis in 200 (12%). Preoperative left ventricular quality was good in 1185 (70%), poor in 508 (30%), and unknown in five patients. Survival at 20 years was as follows: for single-vessel disease, 40%; double-vessel, 26%; triple-vessel, 20%; and left main, 25%. At 20 years of follow-up, 67% of surviving patients were asymptomatic and 26% were improved. Antianginal drug therapy consisted of nitrates in 49% of patients and beta-blockers in 26%. Graft patency at 0 to 5 years was 633 of 780 grafts (81%); at 6 to 10 years, 415 of 606 grafts (68%); at 11 to 15 years, 271 of 449 grafts (60%); and at 16 to 20 years, 65 of 140 grafts (46%). Coronary bypass reoperation was performed in 324 patients (19%) and survival of these patients was 62% compared to 37% for nonreoperation patients (p less than 0.05). Cox analysis demonstrated that the major determinants of survival related to age at operation, extent of coronary disease, quality of ventricle, history of stroke, and preoperative congestive heart failure. At 20 years of follow-up of this early experience with coronary bypass, 76% of surviving patients had one or more patent grafts and the probability of freedom from reoperation was 0.62.
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PMID:Long-term results of coronary bypass surgery. Analysis of 1698 patients followed 15 to 20 years. 202 57

Impaired diastolic function of the hypertrophied and stiffened left ventricle is a characteristic feature of hypertrophic cardiomyopathy (Figure 1). Altered left ventricular filling dynamics and reduced left ventricular distensibility or increased left ventricular diastolic chamber stiffness are associated with reduced left ventricular stroke volume, increased left ventricular filling pressures and compressive effects on the coronary microcirculation. These factors contribute importantly to the clinical presentation of many patients, including symptoms of fatigue, dyspnea and angina pectoris. Reduced distensibility results both from factors determining the passive elastic properties of the ventricular chamber (including severity of hypertrophy, fibrosis and cellular disarray) and from factors influencing the rate and extent of active left ventricular relaxation (Figure 2). The factors contributing to impaired relaxation in hypertrophic cardiomyopathy are mediated via either inactivation dependent or load-dependent mechanisms. In laboratory animals, compromise of myocardial inactivation results in a persistent increase in intracellular calcium concentration and in prolonged interaction of the contractile proteins. Additionally, there is evidence for an increased number of active receptors for calcium antagonists and, lastly, for myocardial ischemia (Figure 3). Load-dependent mechanisms include diminished wall tension at the opening of the mitral valve, changes in afterload, contractility and coronary flow. Other factors are nonuniform and asynchronous regional ventricular function due to differing increases in thickness of the ventricular walls and ischemia (Figure 4). Calcium channel blockers exert a favorable influence on left ventricular relaxation and filling (Figure 5); verapamil and diltiazem are preferable to nifedipine. Verapamil increases left ventricular stroke volume without an increase in the end-diastolic pressure (Figure 6), reduces regional asynchrony if present, and leads to a more homogeneous regional diastolic filling (Figure 4).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Left ventricular diastolic function in hypertrophic cardiomyopathy. 202 81

One hundred fifty seven consecutive octogenarians (mean age +/- standard deviation, 82.4 +/- 1.9 years) underwent coronary artery bypass grafting with hypothermia (mean temperature, 21.8 degrees +/- 1.8 degrees C), hyperkalemic cardioplegia, and cardiopulmonary bypass in a 9-year period. Sixty-six percent were male. Preoperatively, 115 patients (73%) were in New York Heart Association functional class IV, with the remainder being in either class III (23%) or class II (4%). Twenty percent of the patients had major complications including postoperative hemorrhage (15), sepsis (9), cerebrovascular accident (6), third-degree heart block (5), renal failure requiring dialysis (1), and pulmonary embolism (1). The 30-day or in-hospital mortality rate was 7.0%. Mean total hospital stay was 26.1 +/- 17.9 days. One-year and 5-year actuarial survival rates were 85% and 62%, respectively. Higher mortality was seen to be associated with New York Heart Association class IV, left ventricular ejection fraction less than 0.40, and lesser values for cardiac output and cardiac index. At the 6-month postoperative follow-up, 73% of the survivors reported that their general health had improved as compared with before operation. This experience demonstrates that for select octogenarians with unmanageable angina pectoris, coronary artery bypass grafting is an effective therapeutic option.
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PMID:Morbidity and mortality after coronary artery bypass in octogenarians. 203 31

More than the character of the blood pressure elevation, the cardiovascular risk profile should be the prognostic guide for antihypertensive therapeutic decision-making. Hypertension tends to occur in association with other risk factors which augment the risk and need to be considered in evaluating the hazard of hypertension, the urgency for treatment, and the choice of treatment. Elevated blood pressure is often accompanied by blood lipid abnormality, obesity, electrocardiograph (ECG) abnormality, glucose intolerance, and elevated fibrinogen and hematocrit, all of which enhance the risk of cardiovascular sequelae of hypertension. Hypertensive patients at particularly increased risk of cardiovascular events are those with an increased total/HDL-cholesterol ratio, ECG abnormality, impaired glucose tolerance, or the cigarette smoking habit. The risk of a cardiovascular event among hypertensive patients varies over more than a 10-fold range depending on the number of these coexistent risk factors. Multivariate risk formulations are available to allow a composite estimate of the joint conditional probability of a cardiovascular outcome in hypertensive patients with multiple risk factors. Since some antihypertensive agents can adversely affect blood lipids, glucose tolerance, or uric acid values, the risk profile must also be taken into account in choosing the optimal antihypertensive therapy. Also, hypertension is commonly associated with angina, myocardial infarction, left ventricular hypertrophy, stroke, or cardiac failure. These too must be taken under consideration in judging the urgency for treatment and the choice of agents. Thus, hypertension is best regarded as a component of a cardiovascular risk profile in implementing optimal therapy and in assessing its efficacy.
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PMID:The clinical heterogeneity of hypertension. 204 9

Twenty-four patients were randomized to a double-blind, triple placebo controlled, latin square protocol to examine the relative efficacy of propranolol or diltiazem given as monotherapy or in combination with isosorbide dinitrate. Treatment phases were preceded and followed by placebo control periods. At the end of each phase, symptom-limited treadmill exercise stress tests were performed, as well as rest and exercise radionuclide ventriculography. Both forms of monotherapy were effective in reducing episodes of angina and nitroglycerin use, and in improving exercise tolerance. Diltiazem monotherapy was associated with slightly higher treadmill times (509.9 +/- 123 s) compared to propranolol (462.7 +/- 131 s, P less than 0.05). The addition of isosorbide dinitrate to either form of monotherapy allowed no further improvement in any of the measured clinical responses. Radionuclide ventriculography showed no significant difference in resting left ventricular function. The addition of isosorbide dinitrate to propranolol showed a reduction in end diastolic volume in keeping with a reduction in preload. In response to exercise, stress-induced left ventricular dysfunction was equal in all groups except for the diltiazem-nitrate combination, which was associated with a higher ejection fraction (56.2 +/- 8.6%) compared to monotherapy (52.6 +/- 10.9%, P less than 0.01). A higher cardiac output could be achieved in the groups treated with diltiazem; this was related to increased heart rate and maintenance of stroke volume. It was concluded that diltiazem is equally effective as propranolol for the treatment of chronic stable angina and, in terms of exercise capacity and cardiac output, superior to beta-blockade. The addition of isosorbide dinitrate appears to impart no overt benefits, but some evidence suggests a reduction in left ventricular decompensation in the face of stress.
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PMID:Clinical response and effects on left ventricular function of isosorbide dinitrate added to propranolol or diltiazem monotherapy in patients with chronic stable angina. 204 86


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