Donald R. Düren

Observations on mechanisms of ventricular tachycardia in man.

SUMMARY Fifty patients with sustained ventricular tachycardia were studied by endocavitary recordings and programmed electrical stimulation. Of 29 patients in whom tachycardia could be initiated, 18 had chronic coronary artery disease and eight had no detectable heart disease. Of 35 patients in whom the tachycardia could be terminated by premature ventricular stimuli, 21 had chronic coronary artery disease and eight had no detectable heart disease.Initiation of tachycardia was facilitated in 18 of 21 patients by pac- ing the ventricle at the slowest possible pacing rate. An inverse relation was found between the prematurity of the tachycardia-initiating premature beat and the interval between the premature beat and the first beat of tachycardia, a finding suggestive of a re-entry mechanism. The role of the specific conduction system in initiation and during tachycardia remains unknown. Stimulation site was found to affect initiation and termination of tachycardia and width of tachycardia zone.

Auditory stimuli as a trigger for arrhythmic events differentiate HERG-related (LQTS2) patients from KVLQT1-related patients (LQTS1)

OBJECTIVE This study was performed to identify a possible relationship between genotype and phenotype in the congenital familial long QT syndrome (cLQTS). BACKGROUND The cLQTS, which occurs as an autosomal dominant or recessive trait, is characterized by QT-interval prolongation on the electrocardiogram and torsade de pointes arrhythmias, which may give rise to recurrent syncope or sudden cardiac death. Precipitators for cardiac events are exercise or emotion and occasionally acoustic stimuli. METHODS The trigger for cardiac events (syncope, documented cardiac arrhythmias, sudden cardiac death) was analyzed in 11 families with a familial LQTS and a determined genotype. RESULTS The families were subdivided in KVLQT1-related families (LQTS1, n = 5) and HERG (human ether-a-gogo-related gene)-related families (LQTS2, n = 6) based on single-strand conformation polymorphism analysis and sequencing. Whereas exercise-related cardiac events dominate the clinical picture of LQTS1 patients, auditory stimuli as a trigger for arrhythmic events were only seen in LQTS2 patients. CONCLUSIONS Arrhythmic events triggered by auditory stimuli may differentiate LQTS2 from LQTS1 patients.

Effect of Procainamide, Propranolol and Verapamil on Mechanism of Tachycardia in Patients With Chronic Recurrent Ventricular Tachycardia

The effect of short-term intravenous administration of procainamide (12 patients), propranolol (4 patients) and verapamil (4 patients) was studied in 12 patients with chronic recurrent sustained ventricular tachycardia. In all patients tachycardia could reproducibly be initiated and terminated with programmed electrical stimulation of the heart. Procainamide (1) lengthened the effective refractory period of the right ventricle, (2) affected the tachycardia zone, (3) reduced ventricular rate during tachycardia, and (4) lengthened the interval between the tachycardia-initiating premature ventricular beat and the first QRS complex of tachycardia. No effect on the refractory period of the right ventricle or the mechanism of tachycardia was seen after administration of propranolol or verapamil. Apart from their therapeutic implications these data suggest that it may be possible to use drugs to study mechanisms of ventricular tachycardia in the human heart.

Effect of amiodarone in the Wolff-Parkinson-White syndrome

The effect of amiodarone in the Wolff-Parkinson-White syndrome was studied with programmed electrical stimulation of the heart in 15 patients. All 15 patients had circus movement tachycardias; 7 also had atrial fibrillation. Programmed electrical stimulation was performed before and after 14 days of oral administration of amiodarone. The effective refractory period of the accessory pathway lengthened in an atrioventricular direction in all patients and in a ventriculoatrial direction in eight patients. The effective refractory period of the atrium and ventricle lengthened in 14 and 12 patients, respectively. After administration of amiodarone, circus movement tachycardia could no longer be initiated in five patients. The zone of tachycardia narrowed in four patients, did not change in two and increased in seven. The effect of amiodarone on initiation of circus movement tachycardia could be related to differences in effect of the drug and in the mechanism of tachycardia in individual patients. In all patients in whom tachycardias could still be initiated after treatment with amiodarone the heart rate during tachycardia was slower than before treatment. This slowing was caused by a decrease in conduction velocity of the circulatory wave in different parts of the tachycardia circuit. The effect of amiodarone in prolonging the refractory period of the accessory pathway makes this drug especially useful in patients with the Wolff-Parkinson-White syndrome and atrial fibrillation.

Second degree block during reciprocal atrioventricular nodal tachycardia.

Of 67 patients with reciprocal atrioventricular (A-V) nodal tachycardia consecutively studied by programmed electrical stimulation of the heart, nine patients showed second degree block toward the ventricle and one patient toward the atrium during tachycardia. In four patients the occurrence of block was critically related to the prematurity of the test stimulus initiating the tachycardia. In three patients block developed following increase in rate of tachycardia. In two patients block could be elicited by introducing premature ventricular stimuli during tachycardia. Our observations indicate that different mechanisms may be responsible for second degree block during reciprocal supraventricular tachycardia. The finding of second degree block during reciprocal supraventricular tachycardia excludes a tachycardia with A-V conduction over the A-V node - His pathway and V-A conduction over an accessory A-V pathway.

Comparison of transthoracic and transesophageal color Doppler flow imaging in patients with mechanical prostheses in the mitral valve position

This study determined the relative value of transthoracic and transesophageal color Doppler flow imaging to systolic flow patterns in the left atrium in different types of mechanical prostheses in the mitral valve. Thirty-nine patients were investigated. Based on clinical findings, 36 of 39 patients had normal prosthetic valve function. Seventeen patients were interrogated within a few days after surgery. Systolic regurgitant jets in the left atrium were absent in all patients by both transthoracic pulsed and color Doppler flow imaging. Using transthoracic continuous wave Doppler, however, jets were demonstrated in 8 of 39 patients (21%). Transesophageal color Doppler flow imaging demonstrated systolic regurgitant jets originating from the prosthesis in all patients. Tilting disc valves showed jets during the entire systole (closure and leakage backflow). Each type of prosthesis generated a specific jet pattern. Pathologic regurgitant jets were crescent-shaped, more extensive and turbulent than jets caused by normal closure and leakage backflow. Thus, transthoracic color Doppler flow imaging is not sensitive for detecting regurgitant jets in mechanical prostheses in the mitral valve. All mechanical prostheses show a specific jet pattern, which should be helpful when transesophageal echocardiography is used to identify pathologic backflow.

Effects of changes in management of active infective endocarditis on outcome in a 25-year period

The clinical outcome and long-term follow-up of 130 consecutive patients (141 episodes) with active infective endocarditis who were treated between 1966 and 1991 were analyzed. There was a shift toward a higher proportion of referred patients (39 to 78%), patients aged > 60 years (11 to 41%) and urgent surgical treatment (11 to 44%). Medical treatment was administered in 98 patients (70%); 30-day mortality was 27%. Surgery was performed in 43 patients (30%), with an operative mortality of 26%; 9 of 14 patients (64%) who underwent operation within the first week of admission died. Patients with severe heart failure are at the highest risk for early mortality (relative risk = 21.1; 95% confidence interval 7.4-60.3). Referred patients were much more often treated surgically than were nonreferred patients (48 versus 14%) and had a lower operative mortality (24 vs 30%). Nonreferred patients were more often treated medically (86 vs 52%) and with lower mortality (19 vs 39%). The total follow-up time was 730 patient-years; only 1 patient was considered lost to follow-up. The overall cumulative 5-year and 10-year survival after hospital discharge for patients after urgent surgery were 84 +/- 7% and 53 +/- 7%, respectively, and for those after medical treatment 84 +/- 5% and 77 +/- 6%, respectively. The probability of remaining free of late events (recurrent endocarditis, late valve replacement or death) during 5 and 10 years for patients after urgent surgery was 84 +/- 7% and 53 +/- 15%, respectively, and for those after medical treatment 59 +/- 6% and 40 +/- 7%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of digitalis in patients with paroxysmal atrioventricular nodal tachycardia.

Atrioventricular (A-V) conduction, ventriculo-atrial conduction and mechanism of tachycardia were studied by programmed electrical stimulation before and after the administration of ouabain in 15 patients suffering from paroxysmal supraventricular re-entrant tachycardia. In 13 patients the tachycardia circuit was confined to the A-V node. In two patients the stimulation study showed that an accessory pathway was used in a ventriculo-atrial direction during tachycardia. Ouabain lengthened the effective and functional refractory period of the A-V node and A-V nodal transmission time in all patients in whom this could be studied. Only six patients showed lengthening in ventriculo-atrial conduction time or refractory period of the ventriculo-atrial conduction system. In seven patients no tachycardia could be initiated after ouabain. The width of the zone of atrial premature beats able to initiate tachycardia (the tachycardia zone) narrowed in five patients, showed no change in two patients, and increased in one patient. In these eight patients the tachycardia zone shifted to longer premature beat intervals. Ouabain resulted in slowing of cardiac rate during tachycardia. Both patients who used an accessory pathway during tachycardia showed no change in width of their tachycardia zone following ouabain administration. Seven patients were restudied two weeks after chronic oral administration of digoxin. The results were similar to those obtained following ouabain administration. This indicates that in patients suffering from paroxysmal A-V nodal tachycardia the effect of chronic oral digoxin administration can be predicted from the study of the effect of ouabain during programmed stimulation of the heart.

Isolated mitral valve prolapse: Chordal architecture as an anatomic basis in older patients

Ten patients with an average age of 58 years underwent valve replacement because of isolated mitral valve prolapse with severe regurgitation. None had clinical evidence of Marfans syndrome or another systemic disease that would indicate that a primary connective tissue disorder was the cause of the prolapse. All 10 patients had a dome configuration of the posterior leaflet and one or more ruptured chordae related to it. The gross morphology of the resected specimens revealed marked deviations in chordal branching and the pattern of anchoring in each of the 10 cases, rendering the most severely affected parts of the leaflets less well supported. Similar changes occurred at sites remote from the principal abnormality. Microscopically, the dominant tissue change was myxomatous transformation within the affected leaflets and chordae with secondary changes at both atrial and ventricular surfaces. These findings could indicate that insufficient chordal support may have promoted the development of the floppy valve through a process of chronic undue and unbalanced stress on the valve tension and closure apparatus. The resultant degeneration of the connective tissues, histologically expressed as myxomatous transformation, may underlie stretching and thus redundance of the leaflets and eventually rupture of chordae. It is suggested that this sequence of events be considered as a possible pathogenetic mechanism of isolated mitral valve prolapse, particularly in the subset of aged patients.

Cardiac aneurysm complicated by Salmonella abscess. A clinicopathologic correlation in two patients.

Two patients have been documented in whom a preexisting left ventricular aneurysm became complicated by myocardial abscess. Presumptive clinical diagnoses of infected pulmonary infarction and recurrent myocardial infarction were made. In each instance the abscess was revealed at necropsy. Histologic studies suggested that the abscess had occurred through direct spread from an infectious mural endocarditis. This mechanism could be related to the nature of the inner coating, which in both instances revealed evidence of organizing thrombosis with incorporation into the wall of the aneurysms. The observations reemphasize the need to consider the possibility of an infectious cardiac complication in every patient who presents with puzzling and nondiagnostic symptoms but in whom signs of an infectious process are present.