Manfred Zehender

Right Ventricular Infarction as an Independent Predictor of Prognosis after Acute Inferior Myocardial Infarction

BACKGROUND Acute inferior myocardial infarction frequently involves the right ventricle. We hypothesized that right ventricular involvement, as diagnosed by ST-segment elevation in the right precordial lead V4R, may affect the prognosis of patients with inferior myocardial infarctions. METHODS In 200 consecutive patients admitted to the hospital with acute inferior myocardial infarctions, we assessed the prevalence and diagnostic accuracy of ST-segment elevation in lead V4R (as compared with four other diagnostic procedures) to identify right ventricular involvement and its prognostic implications for in-hospital and long-term outcomes. RESULTS The in-hospital mortality after inferior myocardial infarction was 19 percent, and major complications occurred in 47 percent of the patients. The presence of ST-segment elevation in lead V4R in 107 patients (54 percent) was highly predictive of right ventricular infarction (sensitivity, 88 percent; specificity, 78 percent; diagnostic accuracy, 83 percent), as compared with the other diagnostic procedures. The patients with ST-segment elevation in lead V4R had a higher in-hospital mortality rate (31 percent vs. 6 percent, P < 0.001) and a higher incidence of major in-hospital complications (64 percent vs. 28 percent, P < 0.001) than did those without ST-elevation in V4R. Multiple logistic-regression analysis showed ST elevation in V4R to be independent of and superior to all other clinical variables available on admission for the prediction of in-hospital mortality (relative risk, 7.7; 95 percent confidence interval, 2.6 to 23) and major complications (relative risk, 4.7; 95 percent confidence interval, 2.4 to 9). The post-hospital course (follow-up, at least 1 year; mean follow-up, 37 months) was similar in patients with and in those without electrocardiographic evidence of right ventricular infarction. CONCLUSIONS Right ventricular involvement during acute inferior myocardial infarction can be accurately diagnosed by the presence of ST-segment elevation in lead V4R, a finding that is a strong, independent predictor of major complications and in-hospital mortality. Electrocardiographic assessment of right ventricular infarction should be routinely performed in all patients with acute inferior myocardial infarctions.

Mode of death in idiopathic dilated cardiomyopathy: A multivariate analysis of prognostic determinants

A total of 110 patients with idiopathic dilated cardiomyopathy were followed prospectively for 53 +/- 8 (range 41 to 69) months to determine prognostic factors identifying patients at risk for sudden death or death from congestive heart failure. During the follow-up period 39 patients died, 14 of congestive heart failure and 25 suddenly. The incidence of cardiac death after 1 year was 18%, after 2 years 35%, and after 4 years 39%. Multivariate logistic regression analysis identified four independent prognostic factors: left ventricular ejection fraction, cardiac index, number of ventricular pairs/24 hours, and atrial rhythm (sinus rhythm or atrial fibrillation). With the final model of logistic regression 77 of 88 patients (88%) could be classified correctly as being at risk for death from chronic heart failure or sudden cardiac death. Patients who were likely to die of congestive heart failure were characterized by a markedly impaired left ventricular function (measured in terms of left ventricular ejection fraction, cardiac index, or both) and a low number of pairs/24 hours. The association between frequent complex ventricular arrhythmias and depressed left ventricular function identifies patients who are at risk for sudden death. The presence of atrial fibrillation significantly increases the risk of sudden death and death from congestive heart failure.

Mechanisms of cardiac arrhythmias and sudden death in transgenic rabbits with long QT syndrome

Long QT syndrome (LQTS) is a heritable disease associated with ECG QT interval prolongation, ventricular tachycardia, and sudden cardiac death in young patients. Among genotyped individuals, mutations in genes encoding repolarizing K+ channels (LQT1:KCNQ1; LQT2:KCNH2) are present in approximately 90% of affected individuals. Expression of pore mutants of the human genes KCNQ1 (KvLQT1-Y315S) and KCNH2 (HERG-G628S) in the rabbit heart produced transgenic rabbits with a long QT phenotype. Prolongations of QT intervals and action potential durations were due to the elimination of IKs and IKr currents in cardiomyocytes. LQT2 rabbits showed a high incidence of spontaneous sudden cardiac death (>50% at 1 year) due to polymorphic ventricular tachycardia. Optical mapping revealed increased spatial dispersion of repolarization underlying the arrhythmias. Both transgenes caused downregulation of the remaining complementary IKr and IKs without affecting the steady state levels of the native polypeptides. Thus, the elimination of 1 repolarizing current was associated with downregulation of the reciprocal repolarizing current rather than with the compensatory upregulation observed previously in LQTS mouse models. This suggests that mutant KvLQT1 and HERG interacted with the reciprocal wild-type alpha subunits of rabbit ERG and KvLQT1, respectively. These results have implications for understanding the nature and heterogeneity of cardiac arrhythmias and sudden cardiac death.

Effects of early reperfusion in acute myocardial infarction on arrhythmias induced by programmed stimulation: A prospective, randomized study

This study compares inducibility of ventricular tachyarrhythmias by programmed electrical stimulation of the heart in patients with myocardial infarction with and without reperfusion after streptokinase therapy. Sixty-two consecutive patients admitted with an acute myocardial infarction were randomized to either combined intravenous and intracoronary streptokinase (streptokinase group) or to standard coronary care unit treatment (control group). Thirty-six of the 62 patients (21 patients from the streptokinase and 15 from the control group) with a first myocardial infarction were studied by programmed ventricular stimulation after a mean of 26 +/- 14 days. No patient had a history of antiarrhythmic drug use or documentation of a ventricular arrhythmia before the initial admission. A sustained ventricular arrhythmia was induced in 10 (48%) of the 21 patients randomized to streptokinase therapy and in all 15 (100%) control patients (p less than 0.001). Sustained monomorphic ventricular tachycardia was induced in 6 (29%) and 10 (67%) patients, respectively (p less than 0.05). To terminate an induced arrhythmia, direct current countershock was required in 33% of patients in the streptokinase group and 73% of patients in the control group (p less than 0.02). Seventeen of the 21 patients treated with streptokinase and no control patient had evidence of early reperfusion 200 +/- 70 minutes after the onset of pain. In comparison with patients without early reperfusion, patients in the reperfused group had a lower maximal serum creatine kinase value (p less than 0.01), a shorter time to peak creatine kinase value (p less than 0.001) and a higher angiographic left ventricular ejection fraction (62 versus 45%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

ECG variants and cardiac arrhythmias in athletes: clinical relevance and prognostic importance.

These findings permit the following conclusions on cardiac changes induced by high-performance sports and high levels of training. Sinus bradycardia and AV block can frequently be observed in athletes, but they do not require attention as long as they are asymptomatic or do not produce pauses exceeding 4 seconds. Persistent rather than transient second-degree AV block or Mobitz second- or third-degree AV block is an extremely unusual finding even in athletes and should be considered a sign of organic lesions until proved otherwise. Supraventricular and AV node ectopic beats are not more frequent in athletes than in the general population except for atrial fibrillation. WPW syndrome is of particular importance, since rapid conduction to the ventricle via the accessory AV pathway is possible, especially if there is a tendency toward atrial fibrillation. Likewise caution is required in athletes with hypertrophic cardiomyopathy. Here hemodynamic deterioration must be anticipated with the occurrence of supraventricular tachycardia. Simple ventricular arrhythmias occur among athletes with the same frequency as in the general population, but they usually disappear with exercise. The occurrence of complex ventricular forms of arrhythmia should always prompt cardiologic examination in search of underlying cardiac disease, particularly hypertrophic or dilated cardiomyopathy. The presence of ventricular arrhythmias without evidence of underlying heart disease does not indicate a special or increased risk of sudden cardiac death. A higher incidence of right and/or left ventricular hypertrophy, exercise-reversible ST elevation, and exercise-reversible changes in T waves (T negativity, sharp and/or excessive T waves) can be considered physiologic changes in the ECGs of athletes. These changes correlate closely with the type of sports activity and degree of training and are reversible when the activity is stopped. Horizontal ST segment depression are by contrast very rare in athletes and should always be clarified by cardiologic examination. Exercise-induced sudden cardiac death in athletes is unusual without preexisting heart disease. The cause of sudden cardiac death among athletes less than 40 years of age can be predominantely ascribed to congenital heart diseases (such as hypertrophic cardiomyopathy or coronary anomalies). In athletes more than 40 years of age and with increasing age, coronary heart disease is the most frequent autopsy finding. A corresponding risk stratification should take these partial dangers into account.

Determinants of prognosis in idiopathic dilated cardiomyopathy as determined by programmed electrical stimulation.

The incidence and prognostic significance of electrically induced ventricular arrhythmias were prospectively assessed in 42 patients with idiopathic dilated cardiomyopathy. All patients underwent 24-hour, long-term electrocardiographic (Holter) monitoring and 30 were analyzed by a signal-averaging vectorcardiographic procedure at entry into the study. Their response to programmed electrical stimulation during basic right ventricular pacing was investigated using 1 and 2 ventricular extrastimuli. A monomorphic tachycardia was not induced in any patient. In 36 patients (86%) polymorphic ventricular arrhythmias were initiated. Three or more induced consecutive ventricular premature complexes occurred in 9 patients (21%), nonsustained polymorphic ventricular tachycardia in 2 (4.8%) and ventricular fibrillation in 1 patient (2.4%). There was no association between electrically induced polymorphic ventricular arrhythmias and the degree of impairment of left ventricular function. Furthermore, the incidence of induced ventricular arrhythmias was not related to the Lown grade or to the total number of ventricular premature complexes during Holter monitoring. A late potential was detected by the averaged vectorcardiogram in only 1 of the 30 patients. During follow-up (mean 16 +/- 7 months) 7 patients died, 5 from chronic congestive heart failure and 2 from sudden cardiac death. No patient had an electrically induced arrhythmia of 3 or more ventricular premature complexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Prosthesis Oversizing in Balloon-Expandable Transcatheter Aortic Valve Implantation Is Associated With Contained Rupture of the Aortic Root

Background— To retrospectively investigate the potential cause of contained rupture of the aortic root in balloon-expandable transcatheter aortic valve implantation (TAVI) by means of pre- and postinterventional multislice computed tomography. Methods and Results— Seventy-two patients (mean age 82±7 years, mean aortic valve area 0.69±0.19 cm2) underwent balloon-expandable TAVI using the EdwardsSAPIEN Transcatheter Heart Valve (23 mm, n=19; 26 mm, n=50; 29 mm, n=3). Aortic annulus dimensions were quantified by multislice computed tomography–based cross-sectional area assessment and average diameter calculation (CAAD) before and after TAVI. Post-TAVI multislice computed tomography data sets were available in 65 patients; contained aortic root rupture was diagnosed in 3 patients. Pre-TAVI CAAD was 23.1±1.8 mm; post-TAVI CAAD was 22.9±1.3 mm. Median relative change in CAAD pre- and post-TAVI was −0.5% (interquartile range, 3.6%). Relative increase of 5% to 10% was observed in 4 patients (1 with contained rupture), relative increase >10% in 2 patients, both with contained rupture. Mean relative oversizing, calculated as the relative difference in diameter between pre-TAVI CAAD and nominal diameter of the selected prosthesis, was 9.8%±7.8%. Relative oversizing was significantly higher in patients with contained rupture compared with patients without contained rupture (24.6%±5.4% versus 9.1%±6.6%; P<0.001). Relative oversizing ≥20% occurred in 6 patients (3 with contained rupture). Conclusions— Contained rupture of the aortic root in balloon-expandable TAVI is associated with severe prosthesis oversizing. Multislice computed tomography–based assessment of aortic annulus dimension in conjunction with adapted sizing guidelines may reduce the incidence of severe oversizing.

Drug-Induced Torsade de Pointes Incidence, Management and Prevention

SummaryTorsade de pointes is a particular form of polymorphic ventricular tachycardia causing few haemodynamic symptoms, but carries a poor prognosis because of recurrence and sudden death in up to 31% of patients. A wide range of agents have been shown to aggravate and even to cause torsade de pointes by prolonging the QT interval or increasing QT dispersion. For the majority of substances the incidence of torsade de pointes remains unclear, but is of the order of 3 to 15% for a wide range of agents. Elicitation of proarrhythmia by drug-induced QT prolongation is mainly based on increased cellular excitability and/or abnormal dispersion of ventricular repolarisation. Torsade de pointes has been shown to be related to bradycardia-dependent early after-depolarisations and/or increased dispersion of repolarisation. Clinically, patients with predisposing factors prior to medication should be considered at risk of drug-mediated proarrhythmia. Typically, torsade de pointes occurs during the first days of antiarrhythmic therapy. During this phase, QT interval measurement and assessment of the QTc time should be performed frequently. Phases of bradycardia or occurrence of ventricular extra beats with a long coupling interval may be of help to identify patients at high risk of proarrhythmic events.As a first attempt in managing this arrhythmia, magnesium sulphate has been shown to be effective in many patients. In case of recurrence of torsade de pointes, the use of a temporary pacemaker with pacing at about 100 to 120 beats/min is the therapy of choice until the causative agent has been completely eliminated.

Prevalence of circadian variations and spontaneous variability of cardiac disorders and ECG changes suggestive of myocardial ischemia in systemic arterial hypertension.

BackgroundSystemic hypertension is a well-known risk factor for coronary artery disease and sudden cardiac death. Recent interest focused on the presence of malignant ventricular arrhythmias (VA) and myocardial ischemia in hypertensive patients and provided a potential link for fatal tachyarrhythmic events. Methods and ResultsWe studied 150 untreated normokalemic hypertensive patients (56±9 years; 56 women and 94 men) without manifest coronary artery disease to determine prevalence, severity, and interaction of VA and significant ST segment changes induced by daily activities. One third of the patients were randomized to 4 weeks of placebo and restudied for spontaneous variability of the two parameters. All patients were included in a 3-year follow-up study. VA were observed in 129 of 150 hypertensive patients (86%) and peaked in the early morning and late afternoon. Twenty-two patients (15%) had ventricular pairs, and 20 patients (13%) had nonsustained ventricular tachycardia. Transient ST segment depression observed in 47 patients (33%; mean incidence, 2.7±0.8 episodes/24 hr) showed a characteristic circadian variation similar to VA and were asymptomatic in 93% of the episodes. At the time of transient ST segment depression, VA increased 4.6 times (p < 0.01). After 4 weeks of placebo, marked variations in the incidence of VA (VA suppression rate −100%, or increase >400%) were observed in 29% of the patients, and in 60% of all patients repetitive VA were present in only one of the two Holter recordings. Day-and-night variations of VA and transient ST segment changes were highly reproducible during the placebo period. After 3 years of follow-up, eight of 146 patients (5%) had suffered myocardial infarction, and five patients had died from cardiac events (three patients died from sudden cardiac death). Logistic regression analysis revealed left ventricular hypertrophy (relative risk, 6.1;p < 0.01) and transient ST segment abnormalities during daily activities (relative risk, 4.4;p < 0.05) to be of independent prognostic significance to predict cardiac events during follow-up instead of repetitive VA (relative risk, 1.3; NS). ConclusionsVA associated with a high spontaneous variability and predominantly asymptomatic transient ST segment changes are common in hypertensives; the interaction of both risk factors may provide an important link for fatal VA. Antiarrhythmic therapy is not to be recommended in the majority of patients. Presence of left ventricular hypertrophy and transient ST segment changes were the most powerful predictors of cardiac events during the follow-up.

Effect of Availability of Transcatheter Aortic-Valve Replacement on Clinical Practice

BACKGROUND Since the adoption of transcatheter aortic-valve replacement (TAVR), questions have been raised about its effect on clinical practice in comparison with the effect of surgical aortic-valve replacement, which is considered the current standard of care. Complete nationwide data are useful in examining how the introduction of a new technique influences previous clinical standards. METHODS We analyzed data on characteristics of patients and in-hospital outcomes for all isolated TAVR and surgical aortic-valve replacement procedures performed in Germany from 2007 to 2013. RESULTS In total, 32,581 TAVR and 55,992 surgical aortic-valve replacement procedures were performed. The number of TAVR procedures increased from 144 in 2007 to 9147 in 2013, whereas the number of surgical aortic-valve replacement procedures decreased slightly, from 8622 to 7048. Patients undergoing TAVR were older than those undergoing surgical aortic-valve replacement (mean [±SD] age, 81.0±6.1 years vs. 70.2±10.0 years) and at higher preoperative risk (estimated logistic EuroSCORE [European System for Cardiac Operative Risk Evaluation], 22.4% vs. 6.3%, on a scale of 0 to 100%, with higher scores indicating greater risk and a score of more than 20% indicating high surgical risk). In-hospital mortality decreased in both groups between 2007 and 2013 (from 13.2% to 5.4% with TAVR and from 3.8% to 2.2% with surgical aortic-valve replacement). The incidences of stroke, bleeding, and pacemaker implantation (but not acute kidney injury) also declined. CONCLUSIONS The use of TAVR increased markedly in Germany between 2007 and 2013; the concomitant reduction in the use of surgical aortic-valve replacement was moderate. Patients undergoing TAVR were older and at higher procedural risk than those undergoing surgical aortic-valve replacement. In-hospital mortality decreased in both groups but to a greater extent among patients undergoing TAVR. (Funded by the Heart Center, Freiburg University.).