European Heart Journal (1992) 13, 1579-1584
Enhanced A-V nodal conduction (Lown-Ganong-Levine syndrome) by congenitally hypoplastic A-V node R. OMETTO, G. THIENE*, D. CORRADO*, M. VINCENZI AND L. ROSSI*
Department of Cardiology. City Hospital, Vicenza and* Department of Pathology, University of Padua, Italy KEY WORDS: Conduction system, congenital heart disease, enhanced A-V nodal conduction, Lown-GanongLevine syndrome. The basic anatomical substrate ofenhanced A-V nodal conduction, manifesting or not as Lown-Ganong-Levine syndrome, is still a controversial issue. We describe the case of a 34-year-old man who presented episodes of ventricular fibrillation. Electrophysiological studies showed that the AH interval was 55 ms, and increased by only 20 ms at paced cycle lengths of 300 ms; atrial pacing induced atrialfibrillation, with a shortest RR interval of 240 ms. Despite verapamil therapy, this patient died suddenly at home. Histological study disclosed a severe A-V node hypoplasia that was evidently congenital in nature; the rest of the conduction system was normal, and no accessory A-V pathways were present. We suggest that enhanced A- V nodal conduction in this patient was due to the developmental defect in the A-V node; this abnormality caused a loss ofspecific impulse-delay ingfunction, and thus allowed rapid, unfiltered atrial impulses to reach the lower A-V junction and ventricles. Introduction Patients with a short P-R interval and a normal QRS complex usually show an A-V conduction abnormality characterized by little or no prolongation of A-V nodal conduction in response to right atrial pacing" 41. called 'enhanced A-V nodal conduction' by Gallagher et a/.'51. This condition may at times be associated with supraventricular tachyarrhythmias, such as atrial flutter, atrial fibrillation and re-entry tachycardias (Lown-GanongLevine syndrome)16', which may conduct to the ventricles at very fast rates'71. These electrocardiographs features may depend on several anatomical substrates, such as: atriofascicular tracts by-passing the A-V node impulse delaying area'8""1; transitional fibres overlying the A-V node core1'2'; a dual A-V pathway1'3141, and defective A-V node development'415'. Brechenmacher identified a short P-R interval and a normal QRS complex in one of his cases with atriofascicular ('atrio-His bundle') tracts: 'the PR interval was rather short (012 s) and the QRS complex was narrow (008 s)''9'. However, in the few other cases of LownGanong-Levine syndrome that were extensively studied histologically, the observed conduction system changes were more complex than the expected presence of atriofascicular or overlayfibres'16"201;in particular, hypoplasia of the A-V node was never found. On the other hand, atriofascicular tracts were detected in a number of autopsy hearts with no history of Lown-Ganong-Levine Submitted for publication on 5 September 1991, and in revised form 22 January 1992. Presented at the 63rd Scientific Session of the American Heart Associauon, Dallas, 12-15 November, 1990. Supported by the National Council for Research, Target Project FAT MA, Rome, Italy Correspondence- Gaetano Thiene, MD, Istituto di Anatomia Palologica, Via A. Gabelli, 61,35121 Padova, Italy. 0195-668X/92/111579 + 06 $08.00/0
syndrome1[11.21] as well as in victims of unexplained sudden death in whom diagnostic electrocardiograms were not available122291. In view of these clinicopathological doubts concerning the basic features of enhanced A-V nodal conduction and the Lown-Ganong-Levine syndrome, we report a case of sudden death in which both electrophysiological and histological findings are well documented. Case report The patient was an apparently well 34-year-old truck driver, who smoked 40-60 cigarettes per day. In August 1982, he was seen to fall on the steering wheel while driving, and to lose consciousness. He was promptly transferred to the Hospital of S. Bortolo in Vicenza, and on arrival was found to be in ventricular fibrillation. Cardiopulmonary resuscitation was performed and defibrillation was successfully accomplished. Following a few days in the Intensive Care Unit, he was transferred to the Cardiology Division. Examination disclosed cardiac clinical findings within normal limits. ECG showed a sinus rhythm, a PR interval of 0-12 s, and a QRS complex of 008 s; a 1 mm ST depression and inverted T waves in V4-V6 were present. Ambulatory monitoring for 24 h demonstrated rare, unifocal ventricular premature beats (VPBs)(< 1 . h" 1 ). During the exercise stress test, a 1 mm increase in the ST depression was observed at the maximal heart rate of 170 b . min ' with no chest pain. Chest X-ray showed a normal cardio-thoracic ratio; the echocardiographic findings were normal. The results of routine haematological and biochemical studies were within normal limits. Cardiac catheterization showed normal heart pressures; left ventricular and coronary angiograms were normal. The patient was discharged on verapamil 240 mg. day"'. © 1992 The European Society of Cardiology
1580 R. Ometto et al.
Figure I 12-lead ECG showing sinus rhythm, a PR interval of 0- 12 s and a normal QRS complex with non-specific alterations in repolarization
A.
A
LRA
HIS
200 m»
Figure2 From top to bottom, ECG leads I, II, V,, high right atrium (HRA), low right atrium (LRA) and His bundle electrogTam (HIS). The AH and HV intervals are 55 and 40 ms, respectively, at a spontaneous sinus cycle length (CL) of 735 ms.
He returned for a clinical control only 2 years later. He had spontaneously discontinued medication and said he was well, but reported some episodes of palpitation. Ambulatory monitoring showed only seven isolated VPBs in 24 h; ECG showed a P-R interval of 012 s at a rate of 75 b . min~' and a normal QRS complex with non-specific alterations in repolarization (Fig. 1). The patient then underwent electrophysiologic evaluation. ELECTROPHYSIOLOGICAL STUDIES
At time of the study, the patient was in sinus rhythm with a cycle length of 735 ms. The A-H interval, measured from the onset of the first rapid atrial deflection to the beginning of the His bundle deflection, was 55 ms, and the H-V interval was 40 ms (Fig. 2). The right atrium was
paced at increasing rates with steps of 10 b . min '. As the paced cycle lengths were decreased from 700 to 300 ms, the A-H interval increased slightly from 55 to 75 ms, while the H-V interval and QRS complexes remained unchanged (Fig. 3(a)). Ventricular pacing was performed from the right ventricular inflow and outflow chambers; ventriculo-atrial conduction time (V-A) showed no increase at a fixed-rate pacing cycle length of 600 ms to 300 ms (Fig. 3(b)). Atrial extrastimulus testing from the right atrium, coupled to a basic cycle length of 600 and 500 ms, was performed. Figure 4(a) shows the graph relating the A,-A2 to the H,-H2 intervals; the curve descended in close proximity to the line of identity from late diastole to an A,-A2 interval of 240 ms, and then rose slightly until the effective refractory period of the A-V node was reached, at an A,-A2 interval of 180 ms. The retrograde refractory period curve was similar to the anterograde curve; it first descended almost along the line of identity until the V,-V2 interval was 260 ms, and then rose slightly in its terminal phase (Fig. 4(b)). The atrial activation sequence was characterized by inscription of A2 in the His bundle electrogram earlier than in coronary sinus and in high atrium electrograms. Fixed-rate atrial pacing and a single atrial extrastimulus could induce episodes of sustained atrial flutter and fibrillation with very fast rates (Fig. 5). Sustained ventricular arrhythmias were not induced with up to three ventricular extrastimuli. Verapamil (240 mg. day' 1 ) was prescribed at discharge. The patient apparently was doing well, but in December 1985 he died suddenly in his sleep. Necropsy findings
The heart weighed 480 g, and the only relevant gross finding was a focal, eccentric atherosclerotic plaque located at the proximal left anterior descending coronary artery. There was no evidence of recent or healed
(o )
(b)
HRA
LRA
HIS
Figure 3 Panel (a). High right atrial pacing at a cycle length (CL) of 300 ms showing 1:1 Av conduction with a small increase in the AH interval (from 55 ms in Fig. 1 to 75 ms). Panel (b). Ventricular pacing at a CL of 300 ms with 1:1 retrograde ventriculo-atrial (V.-A,) conduction. RV = right ventricle; for other abbreviations see legend to Fig. 2. (a)
( b)
600
600
200 A i - A 2 m«
300 V|-V2
400
500
600
mi
Figure 4 Anterograde (a) and retrograde (b) refractory period curves (pacing cycle length of 500 ms). The graphs relating A,-A2 to the H,-H, intervals during atrial pacing, and V,-V2 to the A ,-Aj intervals during ventricular pacing with the extrastimulus technique, are similar and show a first phase almost coincident with the line of identity, and a slightly ascendent terminal phase.
M^^ li
( b)
. -UUUJU.UXUUUIUI " rrrrrTTrrrrninnrrT ,. Figure 5 Atria] flutter (panel a) and atrial fibrillation (panel b) induced during electrophysiological studies with fixed-rate atrial pacing or single atrial extrastimulus. In panel (a), a 2:1 atrial flutter with an R-R interval of 365 ms is present. In panel (b), atrial fibrillation is shown; shortest and average R-R intervals were 240 ms and 295 ms, respectively.
1582 R. Ometto et al.
1 mm
Figure 6 Eccentric fibrous plaque obstructing the proximal left anterior descending coronary artery by about 50%. Weigert-Van Gieson x 18, and reproduced here at a reduction of 70%.
myocardial infarction. At histology, the plaque stenosed the lumen by 50% (Fig. 6). The conduction system was examined according to the serial section technique, as previously described'221. The sino-atrial node and the atrial approaches to the A-V nodal area appeared normal. The A-V node was difficult to recognize, as it consisted of a few slender fibrils of ordinary and transitional myocardium with no evidence of a compact node (Fig. 7). Distally the ordinary and transitional atrial fibres impinged upon a normal penetrating His bundle, which was continuous with regular common bundle bifurcation and bundle branches (Fig. 8). Thus, the histological findings evidenced a profound hypoplasia of the A-V node, with neither 'duality' of the junctional axis, nor presence of accessory A-V tracts by-passing the A-V nodal area. Discussion The current electrophysiological definition of enhanced A-V nodal conduction is as follows: A-H interval in normal sinus rhythm
Enhanced A-V nodal conduction (Lown-Ganong-Levine syndrome) by congenitally hypoplastic A-V node R. OMETTO, G. THIENE*, D. CORRADO*, M. VINCENZI AND L. ROSSI*
Department of Cardiology. City Hospital, Vicenza and* Department of Pathology, University of Padua, Italy KEY WORDS: Conduction system, congenital heart disease, enhanced A-V nodal conduction, Lown-GanongLevine syndrome. The basic anatomical substrate ofenhanced A-V nodal conduction, manifesting or not as Lown-Ganong-Levine syndrome, is still a controversial issue. We describe the case of a 34-year-old man who presented episodes of ventricular fibrillation. Electrophysiological studies showed that the AH interval was 55 ms, and increased by only 20 ms at paced cycle lengths of 300 ms; atrial pacing induced atrialfibrillation, with a shortest RR interval of 240 ms. Despite verapamil therapy, this patient died suddenly at home. Histological study disclosed a severe A-V node hypoplasia that was evidently congenital in nature; the rest of the conduction system was normal, and no accessory A-V pathways were present. We suggest that enhanced A- V nodal conduction in this patient was due to the developmental defect in the A-V node; this abnormality caused a loss ofspecific impulse-delay ingfunction, and thus allowed rapid, unfiltered atrial impulses to reach the lower A-V junction and ventricles. Introduction Patients with a short P-R interval and a normal QRS complex usually show an A-V conduction abnormality characterized by little or no prolongation of A-V nodal conduction in response to right atrial pacing" 41. called 'enhanced A-V nodal conduction' by Gallagher et a/.'51. This condition may at times be associated with supraventricular tachyarrhythmias, such as atrial flutter, atrial fibrillation and re-entry tachycardias (Lown-GanongLevine syndrome)16', which may conduct to the ventricles at very fast rates'71. These electrocardiographs features may depend on several anatomical substrates, such as: atriofascicular tracts by-passing the A-V node impulse delaying area'8""1; transitional fibres overlying the A-V node core1'2'; a dual A-V pathway1'3141, and defective A-V node development'415'. Brechenmacher identified a short P-R interval and a normal QRS complex in one of his cases with atriofascicular ('atrio-His bundle') tracts: 'the PR interval was rather short (012 s) and the QRS complex was narrow (008 s)''9'. However, in the few other cases of LownGanong-Levine syndrome that were extensively studied histologically, the observed conduction system changes were more complex than the expected presence of atriofascicular or overlayfibres'16"201;in particular, hypoplasia of the A-V node was never found. On the other hand, atriofascicular tracts were detected in a number of autopsy hearts with no history of Lown-Ganong-Levine Submitted for publication on 5 September 1991, and in revised form 22 January 1992. Presented at the 63rd Scientific Session of the American Heart Associauon, Dallas, 12-15 November, 1990. Supported by the National Council for Research, Target Project FAT MA, Rome, Italy Correspondence- Gaetano Thiene, MD, Istituto di Anatomia Palologica, Via A. Gabelli, 61,35121 Padova, Italy. 0195-668X/92/111579 + 06 $08.00/0
syndrome1[11.21] as well as in victims of unexplained sudden death in whom diagnostic electrocardiograms were not available122291. In view of these clinicopathological doubts concerning the basic features of enhanced A-V nodal conduction and the Lown-Ganong-Levine syndrome, we report a case of sudden death in which both electrophysiological and histological findings are well documented. Case report The patient was an apparently well 34-year-old truck driver, who smoked 40-60 cigarettes per day. In August 1982, he was seen to fall on the steering wheel while driving, and to lose consciousness. He was promptly transferred to the Hospital of S. Bortolo in Vicenza, and on arrival was found to be in ventricular fibrillation. Cardiopulmonary resuscitation was performed and defibrillation was successfully accomplished. Following a few days in the Intensive Care Unit, he was transferred to the Cardiology Division. Examination disclosed cardiac clinical findings within normal limits. ECG showed a sinus rhythm, a PR interval of 0-12 s, and a QRS complex of 008 s; a 1 mm ST depression and inverted T waves in V4-V6 were present. Ambulatory monitoring for 24 h demonstrated rare, unifocal ventricular premature beats (VPBs)(< 1 . h" 1 ). During the exercise stress test, a 1 mm increase in the ST depression was observed at the maximal heart rate of 170 b . min ' with no chest pain. Chest X-ray showed a normal cardio-thoracic ratio; the echocardiographic findings were normal. The results of routine haematological and biochemical studies were within normal limits. Cardiac catheterization showed normal heart pressures; left ventricular and coronary angiograms were normal. The patient was discharged on verapamil 240 mg. day"'. © 1992 The European Society of Cardiology
1580 R. Ometto et al.
Figure I 12-lead ECG showing sinus rhythm, a PR interval of 0- 12 s and a normal QRS complex with non-specific alterations in repolarization
A.
A
LRA
HIS
200 m»
Figure2 From top to bottom, ECG leads I, II, V,, high right atrium (HRA), low right atrium (LRA) and His bundle electrogTam (HIS). The AH and HV intervals are 55 and 40 ms, respectively, at a spontaneous sinus cycle length (CL) of 735 ms.
He returned for a clinical control only 2 years later. He had spontaneously discontinued medication and said he was well, but reported some episodes of palpitation. Ambulatory monitoring showed only seven isolated VPBs in 24 h; ECG showed a P-R interval of 012 s at a rate of 75 b . min~' and a normal QRS complex with non-specific alterations in repolarization (Fig. 1). The patient then underwent electrophysiologic evaluation. ELECTROPHYSIOLOGICAL STUDIES
At time of the study, the patient was in sinus rhythm with a cycle length of 735 ms. The A-H interval, measured from the onset of the first rapid atrial deflection to the beginning of the His bundle deflection, was 55 ms, and the H-V interval was 40 ms (Fig. 2). The right atrium was
paced at increasing rates with steps of 10 b . min '. As the paced cycle lengths were decreased from 700 to 300 ms, the A-H interval increased slightly from 55 to 75 ms, while the H-V interval and QRS complexes remained unchanged (Fig. 3(a)). Ventricular pacing was performed from the right ventricular inflow and outflow chambers; ventriculo-atrial conduction time (V-A) showed no increase at a fixed-rate pacing cycle length of 600 ms to 300 ms (Fig. 3(b)). Atrial extrastimulus testing from the right atrium, coupled to a basic cycle length of 600 and 500 ms, was performed. Figure 4(a) shows the graph relating the A,-A2 to the H,-H2 intervals; the curve descended in close proximity to the line of identity from late diastole to an A,-A2 interval of 240 ms, and then rose slightly until the effective refractory period of the A-V node was reached, at an A,-A2 interval of 180 ms. The retrograde refractory period curve was similar to the anterograde curve; it first descended almost along the line of identity until the V,-V2 interval was 260 ms, and then rose slightly in its terminal phase (Fig. 4(b)). The atrial activation sequence was characterized by inscription of A2 in the His bundle electrogram earlier than in coronary sinus and in high atrium electrograms. Fixed-rate atrial pacing and a single atrial extrastimulus could induce episodes of sustained atrial flutter and fibrillation with very fast rates (Fig. 5). Sustained ventricular arrhythmias were not induced with up to three ventricular extrastimuli. Verapamil (240 mg. day' 1 ) was prescribed at discharge. The patient apparently was doing well, but in December 1985 he died suddenly in his sleep. Necropsy findings
The heart weighed 480 g, and the only relevant gross finding was a focal, eccentric atherosclerotic plaque located at the proximal left anterior descending coronary artery. There was no evidence of recent or healed
(o )
(b)
HRA
LRA
HIS
Figure 3 Panel (a). High right atrial pacing at a cycle length (CL) of 300 ms showing 1:1 Av conduction with a small increase in the AH interval (from 55 ms in Fig. 1 to 75 ms). Panel (b). Ventricular pacing at a CL of 300 ms with 1:1 retrograde ventriculo-atrial (V.-A,) conduction. RV = right ventricle; for other abbreviations see legend to Fig. 2. (a)
( b)
600
600
200 A i - A 2 m«
300 V|-V2
400
500
600
mi
Figure 4 Anterograde (a) and retrograde (b) refractory period curves (pacing cycle length of 500 ms). The graphs relating A,-A2 to the H,-H, intervals during atrial pacing, and V,-V2 to the A ,-Aj intervals during ventricular pacing with the extrastimulus technique, are similar and show a first phase almost coincident with the line of identity, and a slightly ascendent terminal phase.
M^^ li
( b)
. -UUUJU.UXUUUIUI " rrrrrTTrrrrninnrrT ,. Figure 5 Atria] flutter (panel a) and atrial fibrillation (panel b) induced during electrophysiological studies with fixed-rate atrial pacing or single atrial extrastimulus. In panel (a), a 2:1 atrial flutter with an R-R interval of 365 ms is present. In panel (b), atrial fibrillation is shown; shortest and average R-R intervals were 240 ms and 295 ms, respectively.
1582 R. Ometto et al.
1 mm
Figure 6 Eccentric fibrous plaque obstructing the proximal left anterior descending coronary artery by about 50%. Weigert-Van Gieson x 18, and reproduced here at a reduction of 70%.
myocardial infarction. At histology, the plaque stenosed the lumen by 50% (Fig. 6). The conduction system was examined according to the serial section technique, as previously described'221. The sino-atrial node and the atrial approaches to the A-V nodal area appeared normal. The A-V node was difficult to recognize, as it consisted of a few slender fibrils of ordinary and transitional myocardium with no evidence of a compact node (Fig. 7). Distally the ordinary and transitional atrial fibres impinged upon a normal penetrating His bundle, which was continuous with regular common bundle bifurcation and bundle branches (Fig. 8). Thus, the histological findings evidenced a profound hypoplasia of the A-V node, with neither 'duality' of the junctional axis, nor presence of accessory A-V tracts by-passing the A-V nodal area. Discussion The current electrophysiological definition of enhanced A-V nodal conduction is as follows: A-H interval in normal sinus rhythm
