Jan G.P. Tijssen

QTc prolongation measured by standard 12-lead electrocardiography is an independent risk factor for sudden death due to cardiac arrest.

BackgroundQTc prolongation has been implicated as a risk factor for sudden death; however, a controversy exists over its significance. Methods and ResultsIn the Rotterdam QT Project, 6,693 consecutive patients who underwent 24-hour ambulatory electrocardiography were followed up for 2 years; of these, 245 patients died suddenly. A standard 12-lead electrocardiogram and clinical data at the time of 24-hour ambulatory electrocardiography were collected for all patients who died suddenly and for a random sample of 467 patients from the study cohort. In all patients without an intraventric-ular conduction defect (176 patients who died suddenly and 390 patients from the sample), QT interval duration was measured in leads I, II, and III and corrected for heart rate with Bazetts formula (QTc). In patients without evidence of cardiac dysfunction (history of symptoms of pump failure or an ejection fraction < 40%), QTc of more than 440 msec was associated with a 2.3 times higher risk for sudden death compared with a QTc of 440 msec or less (95% confidence interval: 1.4, 3.9). In contrast, in patients with evidence of cardiac dysfunction, the relative risk of QTc prolongation was 1.0 (0.5, 1.9). Adjustment for age, gender, history of myocardial infarction, heart rate, and the use of drugs did not alter these relative risks. ConclusionsThese data indicate that in patients without intraventricular conduction defects and cardiac dysfunction, QTc prolongation measured from the standard electrocardiogram is a risk factor for sudden death independent of age, history of myocardial infarction, heart rate, and drug use. In patients with cardiac dysfunction, QTc duration is not related to the risk for sudden death. (Circulation 1991;83:1888—1894)

Heart rate variability from 24-hour electrocardiography and the 2-year risk for sudden death.

BACKGROUND Low heart rate variability has been implicated as a risk factor for sudden death. However, no large epidemiological studies using sudden death as an outcome event have been reported. METHODS AND RESULTS A total of 6,693 consecutive patients who underwent 24-hour ambulatory ECG were followed up for 2 years; of these, 245 patients died suddenly. Clinical data at the time of 24-hour ambulatory ECG were collected for all patients who died suddenly and for a random sample of 268 patients from the study cohort. In all patients in sinus rhythm with or without occasional supraventricular arrhythmias at the 24-hour ECG (193 patients who died suddenly and 230 patients from the sample), heart rate variability parameters were derived. Patients with low short-term RR interval variability (mean during 24 hours of per-minute standard deviations [SD] of RR intervals < 25 msec) had a 4.1-fold higher risk (95% confidence interval [CI], 2.6, 8.1) for sudden death than patients with high short-term variability (> or = 40 msec); after adjustment for age, evidence of cardiac dysfunction, and history of myocardial infarction, the relative risk was 2.6 (95% CI, 1.4, 5.1). The crude relative risk of long-term RR interval variability (SD during 24 hours of per-minute means of RR intervals < 8 msec) was 4.4 (95% CI, 2.6, 7.7); after adjustment for the same risk factors, it was 2.2 (95% CI, 1.2, 4.1). Patients with a minimum heart rate > or = 65 beats per minute had a double risk of sudden death compared with those with a minimum heart rate < 65 beats per minute (adjusted relative risk, 2.1; 95% CI, 1.3, 3.6). CONCLUSIONS These findings support the theory that patients with low parasympathetic activity (low short-term RR interval variability) have an increased risk for sudden death independent of other risk factors.

Long-term benefit of early thrombolytic therapy in patients with acute myocardial infarction: 5 year follow-up of a trial conducted by the Interuniversity Cardiology Institute of the Netherlands

Patients (n = 533) who participated in the Interuniversity Cardiology Institute of the Netherlands Trial were followed up for 3 to 7 years. The 5 year survival rate after thrombolytic therapy with intracoronary streptokinase was 81% (269 patients) compared with 71% after conventional therapy (264 patients). The greatest improvement in survival was observed in patients with anterior infarction (81% versus 64% with thrombolytic therapy or conventional therapy, respectively), in those with heart failure on admission or a previous infarction and in those with extensive myocardial ischemia on admission. Left ventricular ejection fraction at the time of hospital discharge was better after thrombolytic therapy. In the hospital survivors, long-term outcome was related to left ventricular function at the time of discharge and, to a lesser extent, to the underlying coronary artery disease. The initial therapy (thrombolysis or conventional) was not an independent additional determinant of long-term survival when left ventricular function and coronary status at the time of hospital discharge were taken into account. Thus, the salutary effects of thrombolytic therapy appear to be the result of myocardial salvage. Reinfarction within 3 years was observed more frequently after thrombolytic therapy, particularly in patients with inferior wall infarction and those with greater than or equal to 90% stenosis of the infarct-related vessel at discharge. Coronary bypass surgery and coronary angioplasty were performed more frequently after thrombolytic therapy than in conventionally treated patients. At 5 years, approximately 40% of patients in both groups had an uneventful course without reinfarction or additional revascularization procedures. These observations demonstrate that the benefits of thrombolytic therapy are maintained throughout 5 years of follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Luminal narrowing after percutaneous transluminal coronary angioplasty. A study of clinical, procedural, and lesional factors related to long-term angiographic outcome. Coronary Artery Restenosis Prevention on Repeated Thromboxane Antagonism (CARPORT) Study Group.

BACKGROUND The renarrowing process after successful percutaneous transluminal coronary angioplasty (PTCA) is now believed to be caused by a response-to-injury vessel wall reaction. The magnitude of this process can be assessed by the change in minimal lumen diameter (MLD) at follow-up angiography. The aim of the present study was to find independent patient-related, lesion-related, and procedure-related risk factors for this luminal narrowing process. A model that accurately predicts the amount of luminal narrowing could be an aid in patient or lesion selection for the procedure, and it could improve assessment of medium-term (6 months) prognosis. Modification or control of the identified risk factors could reduce overall restenosis rates, and it could assist in the selection of patients at risk for a large loss in lumen diameter. This population could then constitute the target population for pharmacological intervention studies. METHODS AND RESULTS Quantitative angiography was performed on 666 successfully dilated lesions at angioplasty and at 6-month follow-up. Multivariate linear regression analysis was performed to obtain variables with an independent contribution to the prediction of the absolute change in minimal lumen diameter. Diabetes mellitus, duration of angina < 2.3 months, gain in MLD at angioplasty, pre-PTCA MLD, lesion length > or = 6.8 mm, and thrombus after PTCA were independently predictive of change in MLD. Overall prediction of the model was poor, however, percentage-correct classification for a predicted change between -0.1 to -0.4 mm was approximately 10%. Lesions showing no change or regression (change > -0.1 mm) and lesions showing large progression (< or = -0.4 mm) were more predictable (correct classification, 59.5% and 49.7%, respectively). CONCLUSIONS Renarrowing after successful PTCA as determined with contrast angiography is a process that cannot be accurately predicted by simple clinical, morphological, and lesion characteristics.

Lumen narrowing after percutaneous transluminal coronary balloon angioplasty follows a near gaussian distribution: A quantitative angiographic study in 1,445 successfully dilated lesions

To determine whether significant angiographic narrowing and restenosis after successful coronary balloon angioplasty is a specific disease entity occurring in a subset of dilated lesions or whether it is the tail end of a gaussian distributed phenomenon, 1,445 successfully dilated lesions were studied before and after coronary angioplasty and at 6-month follow-up study. The original cohort consisted of 1,353 patients of whom 1,232 underwent repeat angiography with quantitative analysis (follow-up rate 91.2%). Quantitative angiography was carried out off-line in a central core laboratory with an automated edge detection technique. Analyses were performed by analysts not involved with patient care. Distributions of minimal lumen diameter before angioplasty (1.03 +/- 0.37 mm), after angioplasty (1.78 +/- 0.36 mm) and at 6-month follow-up study (1.50 +/- 0.57 mm) as well as the percent diameter stenosis at 6-month follow-up study (44 +/- 19%) were assessed. The change in minimal lumen diameter from the post-angioplasty angiogram to the follow-up angiogram was also determined (-0.28 +/- 0.52 mm). Seventy lesions progressed toward total occlusion at follow-up. All observed distributions approximately followed a normal or gaussian distribution. Therefore, restenosis can be viewed as the tail end of an approximately gaussian distributed phenomenon, with some lesions crossing a more or less arbitrary cutoff point, rather than as a separate disease entity occurring in some lesions but not in others.

Retardation and arrest of progression or regression of coronary artery disease: A review

THEROSCLEROSIS A is the most common cause of death in the Western world accounting for one half of all deaths.’ Hypercholesterolemia, smoking, hypertension, diabetes mellitus, obesity, and physical inactivity are identified as risk factors for this disease.2-h Control of all these factors is desirable, but cholesterol lowering has showed the greatest promise as regards reduction of cardiac events.’ Both primary and secondary intervention trials?-’ I have demonstrated that cardiac mortality decreases after lowering of plasma cholesterol levels, although total mortality was not impact-

Recombinant tissue-type plasminogen activator and immediate angioplasty in acute myocardial infarction. One-year follow-up. The European Cooperative Study Group.

BackgroundThe European Cooperative Study Group conducted two randomized trials in patients with suspected myocardial infarction to assess the effect of 100 mg single-chain recombinant tissue-type plasminogen activator (rt-PA, alteplase) on enzymatic infarct size, left ventricular function, morbidity and mortality relative to placebo (alteplase/placebo trial) and to assess the effect of immediate percutaneous transluminal coronary angioplasty (PTCA) in addition to alteplase (alteplase/PICA trial). One-year follow-up results are reported. Methods and ResultsIn the alteplase/placebo trial, 721 patients with chest pain of less than 5 hours and extensive ST-segment elevation were allocated at random to 100 mg alteplase or placebo (double-blind) over 3 hours. In the alteplase/PTCA trial, 367 similar patients received alteplase and subsequently were allocated at random to immediate coronary angiography and angioplasty of the infarct-related vessel or control. All patients received aspirin and intravenous heparin. In the alteplase/placebo trial, mortality during the first year was reduced by 36% with alteplase (from 9.3% to 5.6%; difference, −3.7%; 95% confidence interval, −7.5% to 0.2%). Revascularization was performed more frequently after alteplase, and more patients in the alteplase group were in New York Heart Association functional class I or H. Reinfarction tended to occur more frequently after alteplase than after placebo. In the alteplase/PTCA trial, reinfarction was less common after immediate PICA, and revascularization procedures were less frequent. However, this benefit was offset by a high rate of immediate reocclusion and early recurrent ischemia and by higher mortality at 1 year (9.3% versus 5.4%; difference, 3.9%; 95% confidence interval, −1.5% to 9.2%) in the invasive group. In a multivariate analysis of 1,043 hospital survivors, mortality after discharge was related to coronary anatomy, left ventricular function, age, and previous infarction but not to initial treatment allocation. Reinfarction after hospital discharge tended to be more common after alteplase and related to coronary anatomy. ConclusionsBenefit from treatment with alteplase, heparin, and aspirin is not diminished at 1 year. Routine immediate PTCA does not confer additional benefit. Prognosis after hospital discharge mainly is determined by coronary anatomy and residual left ventricular function and is unrelated to initial treatment assignment.

Determinants of prognosis in symptomatic ventricular tachycardia or ventricular fibrillation late after myocardial infarction

In a multicenter study, 390 patients with sustained symptomatic ventricular tachycardia or ventricular fibrillation late after acute myocardial infarction were prospectively followed up to assess determinants of mortality and recurrence of arrhythmic events. Patients were given standard antiarrhythmic treatment, which consisted primarily of drug therapy. During a mean follow-up period of 1.9 years, 133 patients (34%) died; arrhythmic events and heart failure were the most common cause of death (41 patients [11%] died suddenly, 31 [8%] died of recurrent ventricular tachycardia or ventricular fibrillation and 23 [6%] died of heart failure). One hundred ninety-two patients (49%) had at least one recurrent arrhythmic event; 85% of first recurrent arrhythmic events were nonfatal. Multivariate analysis of data from patients who developed the arrhythmia 70 years (risk ratio 4.5); 2) Killip class III or IV in the subacute phase of infarction (risk ratio 3.5); 3) cardiac arrest during the index arrhythmia (risk ratio 1.7); 4) anterior infarction (risk ratio 2.2); and 5) multiple previous infarctions (risk ratio 1.6). Multivariate analysis of data from patients developing the arrhythmia >6 weeks after infarction identified four variables as independently predictive of total mortality: 1) Q wave infarction (risk ratio 2.1); 2) cardiac arrest during the index arrhythmia (risk ratio 1.7); 3) Killip class III or IV in the subacute phase of infarction (risk ratio 1.7); and 4) multiple previous infarctions (risk ratio 1.4). The results of the two multivariate analyses were used in a model for prediction of mortality at 1 year. The average predicted mortality rate varied considerably according to the model: for 243 patients (62%) with the lowest risk, it was 13%, corresponding to an observed mortality rate of 12%; for 92 patients (24%) with intermediate risk, it was 27%, corresponding to an observed rate of 28%; for 55 patients (14%) with the risk, it was 64%, corresponding to an observed rate of 54%. This study shows that patients with symptomatic ventricular tachycardia or ventricular fibrillation late after myocardial infarction who are given standard antiarrhythmic treatment have a high mortality rate. The predictive model presented identifies patients at low, intermediate and high risk of death and can be of help in designing the appropriate diagnostic and therapeutic strategy for the individual patient.In a multicenter study, 390 patients with sustained symptomatic ventricular tachycardia or ventricular fibrillation late after acute myocardial infarction were prospectively followed up to assess determinants of mortality and recurrence of arrhythmic events. Patients were given standard antiarrhythmic treatment, which consisted primarily of drug therapy. During a mean follow-up period of 1.9 years, 133 patients (34%) died; arrhythmic events and heart failure were the most common cause of death (41 patients [11%] died suddenly, 31 [8%] died because of recurrent ventricular tachycardia or ventricular fibrillation and 23 [6%] died of heart failure). One hundred ninety-two patients (49%) had at least one recurrent arrhythmic event; 85% of first recurrent arrhythmic events were nonfatal. Multivariate analysis of data from patients who developed the arrhythmia less than 6 weeks after infarction identified five variables as independent determinants of total mortality: 1) age greater than 70 years (risk ratio 4.5); 2) Killip class III or IV in the subacute phase of infarction (risk ratio 3.5); 3) cardiac arrest during the index arrhythmia (risk ratio 1.7); 4) anterior infarction (risk ratio 2.2); and 5) multiple previous infarctions (risk ratio 1.6). Multivariate analysis of data from patients developing the arrhythmia greater than 6 weeks after infarction identified four variables as independently predictive of total mortality: 1) Q wave infarction (risk ratio 2.1); 2) cardiac arrest during the index arrhythmia (risk ratio 1.7); 3) Killip class III or IV in the subacute phase of infarction (risk ratio 1.7); and 4) multiple previous infarctions (risk ratio 1.4). The results of the two multivariate analyses were used in a model for prediction of mortality at 1 year. The average predicted mortality rate varied considerably according to the model: for 243 patients (62%) with the lowest risk, it was 13%, corresponding to an observed mortality rate of 12%; for 92 patients (24%) with intermediate risk, it was 27%, corresponding to an observed rate of 28%; for 55 patients (14%) with the highest risk, it was 64%, corresponding to an observed rate of 54%. This study shows that patients with symptomatic ventricular tachycardia or ventricular fibrillation late after myocardial infarction who are given standard antiarrhythmic treatment have a high mortality rate. The predictive model presented identifies patients at low, intermediate and high risk of death and can be of help in designing the appropriate diagnostic and therapeutic strategy for the individual patient.

Quantitative Echocardiographic Analysis of Global and Regional Left Ventricular Function: A Problem Revisited

We recorded two-dimensional echocardiograms simultaneously with the respiration measurements of 20 normal subjects and 20 patients with anterior myocardial infarction. The apical long-axis and four-chamber views were quantitatively analyzed. Measurement variability of global ejection fraction and regional ejection fraction of 100 regions was calculated during inspiration and at end-expiration for two observers. To minimize variability, the endocardial contour was redefined and traced with an improved computer-assisted tracing system. Variability (absolute mean difference) between two beats at end-expiration was significantly less than during inspiration (p less than 0.05): for ejection fraction the variability at end-expiration was 3.4% and the variability during inspiration was 6.4% (mean, 54%; SD, 7%); for regional ejection fraction the variability at end-expiration was 11.8% and the variability during inspiration was 21.5% (mean, 56%; SD, 15%). Intraobserver and interobserver variability values of one beat at end-expiration for ejection fraction were 3.1% and 3.8%, respectively, and 9.5% and 12.8%, respectively, for regional ejection fraction. Variability in patients with myocardial infarction was comparable. This method of recording respiration and analyzing left ventricular function at end-expiration, with a new contour definition and tracing system, provides a measurement variability that is considerably less than that reported in previous echocardiographic studies and that is comparable to angiographic methods.

Iloprost (ZK 36374) enhances recovery of regional myocardial function during reperfusion after coronary artery occlusion in the pig.

1 Ligation of the left anterior descending coronary artery in open‐chest pigs for 20 min caused a complete loss of regional myocardial function, which did not recover during the first two hours of reperfusion. 2 Infusion of the stable prostacyclin analogue Iloprost (100 ng kg−1 min−1) did not prevent the loss of systolic wall function during ischaemia. 3 Recovery of regional myocardial function during the first two hours of reperfusion was enhanced to 40% of baseline by Iloprost. 4 This effect of Iloprost cannot be explained by a decreased O2‐demand during ischaemia or an enhanced recovery of myocardial ATP content.