[Historical developments in the diagnosis and treatment of pre-excitation syndromes (WPW)]. / Historische Entwicklung in Diagnostik und Therapie bei Präexzitationssyndromen (WPW).

In 1930, Wolff, Parkinson and White described the syndrome that bears their names. The mechanisms of supraventricular tachycardias were analyzed by brilliant electrocardiography interpretation by Pick and Langendorf. Wellens and Durrer using electrophysiologic studies analyzed the tachycardia mechanism invasively. In Germany the group by Seipel and Breithardt as well as Neuss and Schlepper studied the tachycardia mechanisms and response to antiarrhythmic drugs invasively by electrophysiological studies. Following the first successful interruption of an accessory pathway by Sealy in 1967, surgeons and electrophysiologists cooperated in Germany. Two centers, Hannover and Düsseldorf were established. Direct current (DC) ablation of accessory pathways was introduced by Morady and Scheinman. Because of side effects induced by barotrauma of DC, alternative strategies were studied. In 1987, radiofrequency ablation was introduced and thereafter established as curative therapy of accessory pathways in all locations.

Risk assessment in patients with symptomatic and asymptomatic pre-excitation.

AIMS: Controversy remains as to whether the exercise stress test (EST) is sufficient for risk evaluation in patients with pre-excitation. This study aims to clarify the usefulness of EST in risk stratification in both asymptomatic and symptomatic patients presenting with pre-excitation. METHODS AND RESULTS: This prospective study includes consecutive asymptomatic and symptomatic patients with pre-excitation referred for risk assessment. All participants performed an incremental EST (bicycle) prior to an electrophysiology study (EPS). Primary data from the EST included loss of pre-excitation during exercise, and primary data from the EPS included the measurement of accessory pathway effective refractory period (APERP), shortest pre-excited RR interval (SPERRI), and inducible arrhythmia with the use of a beta-adrenergic receptor agonist if deemed necessary. One hundred and sixty-four patients (59 asymptomatic, 105 symptomatic) completed an EST and EPS. Forty-five patients (27%) demonstrated low-risk findings on EST, of which 19 were asymptomatic and 26 were symptomatic. Six patients with low-risk EST findings had SPERRI/APERP ≤ 250 ms at EPS, and two of them were asymptomatic. The sensitivity, specificity, positive predictive value, negative predictive value (NPV), and accuracy of low-risk EST for excluding patients with SPERRI/APERP ≤ 250 ms were 40, 91, 87, 51, and 60%, respectively. The number of patients with inducible arrhythmia at EPS was similar in the asymptomatic (36, 69%) and symptomatic (73, 61%) groups. CONCLUSION: Sudden loss of pre-excitation during EST has a low NPV in excluding high-risk APs. The EPS with the use of isoproterenol should be considered to accurately assess the risk of patients with pre-excitation regardless of symptoms (ClinicalTrials.gov Identifier: NCT03301935).

[History of surgical treatment of cardiac arrhythmias in Germany : Surgical treatment of ventricular tachycardia and supraventricular tachycardia, especially pre-excitation syndromes (WPW)]. / Geschichte der chirurgischen Behandlung von Herzrhythmusstörungen in Deutschland : Chirurgische Therapie ventrikulärer Tachykardien sowie supraventrikulärer Tachykardien, insbesondere Präexzitationssyndromen (WPW).

The history of surgical treatment of ventricular tachycardias (VT) is short, lasting from 1978 until 1993. "Indirect procedures" with infarct scar resection were performed without electrophysiologic studies, whereas "direct procedures" consisted of either complete endocardial incisions ("encircling endocardial ventriculotomy") or large endocardial resections ("endocardial peel-off" technique) after precise epicardial and endocardial mapping procedures. In Germany, the first to report on intra-operative electrophysiologic mapping for VT treatment were Ostermeyer, Breithardt and Seipel in 1979. In 1981, the Hannover group (Frank, Klein) published their first results of surgical treatment of VT. In 1984, Ostermeyer et al. demonstrated that a partial endocardial incision resulted in more beneficial results with less myocardial damage (8% versus 46%) than applying a complete encircling incision. In 1987, the Düsseldorf group reported treatment results of 93 patients. After 5 years, 77% had no VT recurrence, while total mortality after 1 year was 11% and after 5 years 30%. In 1992, the Hannover group reported results of 147 patients after endocardial resection for VT. Total mortality after 3 years was 27%; recurrence of VT events occurred in 18% of the surviving cohort.The history of surgical procedures for supraventricular tachycardia (SVT), in particular Wolff-Parkinson-White (WPW) syndrome, is even shorter than that of surgery for VT. As early as 1969, Sealy, Gallagher and Cox reported the first cases of surgical intervention for WPW syndrome via endocardial access in cardioplegic arrest. In 1984, Guiraudon and Klein reported on a new procedure with epicardial access to the accessory bundle without cardioplegia in laterally localised conduction pathways. In Germany, too, the groups in Düsseldorf (Ostermeyer, Seipel, Breithardt, Borggrefe) from 1980 and the Hannover group (Frank, Klein and Kallfelz) from 1981 performed surgical procedures for WPW syndrome. In 1987, Borggrefe reported on 18 patients with WPW syndrome and atrial fibrillation who had undergone surgery. After 2 years, 14 of 18 patients had no recurrences of tachycardia; in 1989, Frank, Klein and Kallfelz (Hannover) reported on 10 children (2-14 years) operated on using the cryoablation technique. Between 1984 and 1992, a total of 120 patients with SVT, mostly WPW syndrome, were operated on in Hannover; after 42 months, 12 patients had a recurrence of SVT. Two patients died during the reoperation.

Hypertrophic Cardiomyopathy and Ventricular Preexcitation in the Young: Cause and Accessory Pathway Characteristics.

BACKGROUND: The cause of hypertrophic cardiomyopathy (HCM) in the young is highly varied. Ventricular preexcitation (preexcitation) is well recognized, yet little is known about the specificity for any cause and the characteristics of the responsible accessory pathways (AP). METHODS: Retrospective cohort study of patients <21 years of age with HCM/preexcitation from 2000 to 2022. The cause of HCM was defined as isolated HCM, storage disorder, metabolic disease, or genetic syndrome. Atrioventricular AP (true AP) were distinguished from fasciculoventricular fibers (FVF) using standard invasive electrophysiology study criteria. AP were defined as high risk if any of the following were <250 ms: shortest preexcited RR interval in atrial fibrillation, shortest paced preexcited cycle length, or anterograde AP effective refractory period. RESULTS: We identified 345 patients with HCM and 28 (8%) had preexcitation (isolated HCM, 10/220; storage disorder, 8/17; metabolic disease, 5/19; and genetic syndrome, 5/89). Six (21%) patients had clinical atrial fibrillation (1 with shortest preexcited RR interval <250 ms). Twenty-two patients underwent electrophysiology study which identified 23 true AP and 16 FVF. Preexcitation was exclusively FVF mediated in 8 (36%) patients. Five (23%) patients had AP with high-risk conduction properties (including ≥1 patient in each etiologic group). Multiple AP were seen in 8 (36%) and AP plus FVF in 10 (45%) patients. Ablation was acutely successful in 13 of 14 patients with recurrence in 3. One procedure was complicated by complete heart block after ablation of a high-risk midseptal AP. There were significant differences in QRS amplitude and delta wave amplitude between groups. There were no surface ECG features that differentiated AP from FVF. CONCLUSIONS: Young patients with HCM and preexcitation have a high likelihood of underlying storage disease or metabolic disease. Nonisolated HCM should be suspected in young patients with large QRS and delta wave amplitudes. Surface ECG is not adequate to discriminate preexcitation from a benign FVF from that secondary to potentially life-threatening AP.

Two-dimensional speckle tracking imaging to assess the hazards of left ventricular function and ventricular wall motion disorders in children with pre-excitation syndrome and the efficacy of radiofrequency ablation treatment.

OBJECTIVE: Our study aimed at analyzing the echocardiographic multi-indicator evaluation of the risk of Wolff-Parkinson-White syndrome (WPW) on the left ventricular function and ventricular wall motion disorders, as well as the effect of radiofrequency ablation treatment. PATIENTS AND METHODS: The clinical data of 55 WPW patients treated with radiofrequency (RF) ablation at the Children's Hospital of Nanjing Medical University between January 2018 and December 2022 were retrospectively analyzed and included in the observation group, while other 50 healthy children were included in the control group during the same time. We analyzed the echocardiographic indices of the patients, assessed the effects of the disease on left ventricular myocardial function and ventricular wall motion disorders, and evaluated the effects of radiofrequency ablation treatment on the myocardium of the left ventricle. The echocardiographic parameters were analyzed to assess the effect of the disease on left ventricular myocardial function and ventricular wall dyskinesia. RESULTS: Of the 55 patients with pre-excited syndrome, 20 had type A bypass and 35 had type B bypass. Ten patients had pre-excited dilated cardiomyopathy with significant enlargement of the left ventricular cavity, reduced left ventricular systolic function, and a significant impairment of ventricular wall motion; the other 5 patients had basal segmental septal motion incoordination. Compared to the control group, patients with left ventricular end-diastolic diameter (LVEDD) (42.9±5.0 mm vs. 39.2±3.0 mm), peak strain dispersion (PSD) (38.8±15.3 ms vs. 21.7±2.2 ms), maximum peak time difference (MPTD) (200.2±92.8 ms vs. 89.5±9.8 ms) and interventricular mechanical delay (IVMD) (36.2±13.7 ms vs. 21.2±2.1 ms) before RF ablation were increased. Left ventricular ejection fraction (LVEF) (57.1±9.1% vs. 65.9±2.6%), E/A (1.1±0.2 vs. 1.8±0.2) and global longitudinal strain (GLS) (-18.7±2.2% vs. -22.4±0.5%) decreased, with statistically significant differences (p<0.05). All 55 patients had a successful procedure, and all postoperative echocardiographic parameters were found to be improved, compared to the preoperative period. The results of the postoperative review after 3 months showed differences in E/A, PSD, MPTD, and IVMD compared to the healthy group, suggesting that left ventricular diastolic function and synchrony had not fully returned to normal. CONCLUSIONS: Echocardiography can better evaluate myocardial motion and function in patients with Wolff-Parkinson-White syndrome and monitor the effect and progress of disease treatment, and has high clinical application value.

Intermittent ventricular pre-excitation in symptomatic adults: Always a marker of low risk?

BACKGROUND: Intermittent ventricular pre-excitation was considered a low-risk marker for sudden death. However, to date, some studies do not exclude the existence of accessory pathways (APs) with high-risk intermittent antegrade conductive properties. According to current European Guidelines, high-risk features of APs are antegrade pathway conduction ≤250 ms in baseline or during the adrenergic stimulus, inducibility of atrioventricular reciprocating tachycardias (AVRT), inducibility of pre-excited atrial fibrillation (AF), and presence of multiple APs. For all of these transcatheter ablation is recommended. The aim of our study was to evaluate the existence of differences in risk characteristics between patients with intermittent pre-excitation (IPX) and those with persistent pre-excitation (PPX), from a sample of adults with ventricular pre-excitation and symptoms like palpitations. METHODS: 293 adults [IPX: 51 (17.4%); PPX: 242 (82.6%)] underwent electrophysiological study and then catheter ablation of their APs if arrhythmia inducibility (AVRT/AF) was noted, or, conversely, if it was appreciated a fast AP antegrade conduction, in baseline or during intravenous isoproterenol infusion, or if multiple APs were detected. RESULTS: There were no statistically significant differences in demographic characteristics (age and gender), AVRT/AF inducibility, antegrade conductive properties, the prevalence of multiple APs, and APs locations between IPX and PPX patients. CONCLUSIONS: In our study, patients with IPX did not show significant differences in clinical and electrophysiological features versus PPX patients.

Ventricular pre-excitation in cats: 17 cases.

OBJECTIVES: Atrioventricular accessory pathways are abnormal electrical connections between the atria and ventricles that predispose to ventricular pre-excitation (VPE) and tachycardias. ANIMALS: Seventeen cats with VPE and 15 healthy matched-control cats. MATERIAL AND METHODS: Multicenter case-control retrospective study. Clinical records were searched for cats with VPE, defined as preserved atrioventricular synchrony, reduced PQ interval, and increased QRS complex duration with a delta wave. Clinical, electrocardiography, echocardiographic, and outcome data were collated. RESULTS: Most cats with VPE were male (16/17 cats), non-pedigree cats (11/17 cats). Median age and mean body weight were 5.4 years (0.3-11.9 years) and 4.6 ± 0.8 kg, respectively. Clinical signs at presentation included lethargy (10/17 cats), tachypnea (6/17 cats), and/or syncope (3/17 cats). In two cats, VPE was an incidental finding. Congestive heart failure was uncommon (3/17 cats). Nine (9/17) cats had tachyarrhythmias: 7/9 cats had narrow QRS complex tachycardia and 2/9 cats had wide QRS complex tachycardia. Four cats had ventricular arrhythmias. Cats with VPE had larger left (P < 0.001) and right (P < 0.001) atria and thicker interventricular septum (P = 0.019) and left ventricular free wall (P = 0.028) than controls. Three cats had hypertrophic cardiomyopathy. Treatment included different combinations of sotalol (5/17 cats), diltiazem (5/17 cats), atenolol (4/17 cats), furosemide (4/17 cats), and platelet inhibitors (4/17 cats). Five cats died, all from cardiac death (median survival time 1882 days [2-1882 days]). CONCLUSIONS: Cats with VPE had a relatively long survival, albeit showing larger atria and thicker left ventricular walls than healthy cats.

Ablation of Ventricular Preexcitation to Cure Preexcitation-Induced Dilated Cardiomyopathy in Infants: Diagnosis and Outcome.

BACKGROUND: To investigate the clinical features of preexcitation-induced dilated cardiomyopathy in infants and evaluate safety and efficacy of radiofrequency ablation (RFCA) in these patients. METHODS: This study included 10 infants (4 males and 6 females) with mean age of 6.78±3.14 months, mean weight of 8.11±1.71 kg, and mean left ventricular ejection fraction (LVEF) was 32.6±10.34%. Tachycardiomyopathy has been excluded and all patients were refractory to the drugs. All of these 10 patients underwent RFCA. RESULTS: All the accessory pathways in these patients were located on right free wall and the acute success rate was 100%. No complication associated with the procedure occurred. In one case preexcitation recurred and was ablated successfully during the second attempt. There were 3 patients with mild cardiac dysfunction (LVEF, 40≤LVEF<50%), 3 with moderate (30≤LVEF<40%), and 4 with severe cardiac dysfunction (LVEF<30%, the ages were 3, 6, 7, and 10 months, respectively). The time for LVEF normalization was 1 week, 1 to 3 months, and ≥3 months, respectively. In 3 of the 4 severe cardiac dysfunction patients, the LVEF normalized at 3, 6, and 12 months after ablation, the LVEF of the remaining case did not recover at 3 months and is still being followed. CONCLUSIONS: Ventricular preexcitation could lead to severe cardiac dysfunction during infancy. RFCA may be a safe and effective treatment option in right free wall accessory pathways, even in infants with cardiac dysfunction. Cases of more severe cardiac dysfunction might require a longer time for LVEF recovery after RFCA.

Iatrogenic cardiomyopathy in patients with manifest right supero-paraseptal accessory pathways.

INTRODUCTION: We describe two patients with right supero-paraseptal accessory pathway (SPAP) who developed left ventricular dysfunction associated with an increased degree of ventricular pre-excitation and frequent orthodromic reciprocating tachycardia (ORT) due to worsening atrioventricular (AV) node conduction. METHODS AND RESULTS: Case 1: 48-year-old female with a history of normally functioning mechanical mitral valve, CABG, and ventricular pre-excitation that worsened after her open heart surgery. She presented with frequent palpitations with documented supraventricular tachycardia (SVT) and found to have a new left ventricular dysfunction with decrease in left ventricular ejection fraction (LVEF) from 55% to 46% with dyssynchrony. An electrophysiological study confirmed a right SPAP and ORT. The pathway was successfully ablated from the antegrade approach after careful mapping. After ablation and 6-month follow up echocardiogram showed improvement of EF to 54% and the LV dyssynchrony resolved. Case 2: 51-year-old male with a history of frequent SVT with recent unsuccessful ablations that resulted in worsening ventricular pre-excitation, more frequent SVT, and new left ventricular dysfunction (LVEF from 60% to 40%). He was started on amiodarone which resulted in significant sinus bradycardia, intermittent ventricular pre-excitation, and first degree AV block with significant increase in ORT events. His electrophysiology study confirmed SPAP which was successfully ablated from the antegrade approach after careful mapping. After 1 month, follow-up echocardiogram showed an improved ejection fraction to 60%. CONCLUSION: Left ventricular dysfunction due to dyssynchrony and symptomatic frequent ORT of right SPAP can develop in the setting of new iatrogenic diminished AV node conduction. Successful ablation will result in LV function recovery to baseline.

Wolff-Parkinson-White syndrome and dilated cardiomyopathy: Not only an electrical issue?

The present case describes a dilated cardiomyopathy associated with both antidromic and orthodromic atrio-ventricular reentrant tachycardias supported by multiple right accessory pathways. Both right accessory pathways were successfully eliminated by catheter ablation and the patient progressively recovered during the follow up. The following etiologies might be involved: 1) primitive dilated cardiomyopathy (or post-inflammatory); 2) septal dyssinchrony due to ventricular pre-excitation; 3) tachycardiomyopathy.

[Clinical characteristics of Danon disease].

Objective: To review the clinical data of 7 patients with Danon disease and analyze their clinical characteristics. Methods: The medical records of 7 patients with Danon disease, who were hospitalized in Peking Union Medical College Hospital of Chinese Academy of Medical Sciences from April 2008 to July 2021, were reviewed and summarized, of which 6 cases were diagnosed as Danon disease by lysosomal-associated membrane protein-2 (LAMP-2) gene mutation detection and 1 case was diagnosed by clinicopathological features. Clinical manifestations, biochemical indexes, electrocardiogram, echocardiography, skeletal muscle and myocardial biopsy and gene detection results were analyzed, and patients received clinical follow-up after discharge. Results: Six patients were male and average age was (15.4±3.5) years and the average follow-up time was (27.7±17.0) months. The main clinical manifestations were myocardial hypertrophy (6/7), decreased myodynamia (2/7) and poor academic performance (3/7). Electrocardiogram features included pre-excitation syndrome (6/7) and left ventricular hypertrophy (7/7). Echocardiography examination evidenced myocardial hypertrophy (6/7), and left ventricular dilatation and systolic dysfunction during the disease course (1/7). The results of skeletal muscle biopsy in 6 patients were consistent with autophagy vacuolar myopathy. Subendocardial myocardial biopsy was performed in 3 patients, and a large amount of glycogen deposition with autophagosome formation was found in cardiomyocytes. LAMP-2 gene was detected in 6 patients, and missense mutations were found in all these patients. During the follow-up period, implantable cardioverter defibrillator implantation was performed in 1 patient because of high atrioventricular block 4 years after diagnosis, and there was no death or hospitalization for cardiovascular events in the other patients. Conclusion: The main clinical manifestations of Danon disease are cardiomyopathy, myopathy and mental retardation. Pre-excitation syndrome is a common electrocardiographic manifestation. Autophagy vacuoles can be seen in skeletal muscle and myocardial pathological biopsies. LAMP-2 gene mutation analysis is helpful in the diagnose of this disease.

Left ventricular dysfunction in a child with asymptomatic pre-excitation: Cure with catheter ablation.

Wolff-Parkinson-White syndrome, is known to cause left ventricular dysfunction or dilated cardiomyopathy secondary to sustained tachycardia in infants and children. However, left ventricular dysfunction secondary to pre-excitation related abnormal ventricular activation has been reported in a limited number of cases. This condition should be recognized early, as catheter ablation of the accessory pathway can permit rapid ventricular function improvement. In this paper, we present a 2.5-year-old patient diagnosed with tachycardia-free Wolff-Parkinson-White syndrome with a right free wall accessory pathway and depressed cardiac function, whose left ventricular function is completely restored after successful catheter cryoablation.

Clinical characteristics of Danon disease / 中华心血管病杂志

Objective: To review the clinical data of 7 patients with Danon disease and analyze their clinical characteristics. Methods: The medical records of 7 patients with Danon disease, who were hospitalized in Peking Union Medical College Hospital of Chinese Academy of Medical Sciences from April 2008 to July 2021, were reviewed and summarized, of which 6 cases were diagnosed as Danon disease by lysosomal-associated membrane protein-2 (LAMP-2) gene mutation detection and 1 case was diagnosed by clinicopathological features. Clinical manifestations, biochemical indexes, electrocardiogram, echocardiography, skeletal muscle and myocardial biopsy and gene detection results were analyzed, and patients received clinical follow-up after discharge. Results: Six patients were male and average age was (15.4±3.5) years and the average follow-up time was (27.7±17.0) months. The main clinical manifestations were myocardial hypertrophy (6/7), decreased myodynamia (2/7) and poor academic performance (3/7). Electrocardiogram features included pre-excitation syndrome (6/7) and left ventricular hypertrophy (7/7). Echocardiography examination evidenced myocardial hypertrophy (6/7), and left ventricular dilatation and systolic dysfunction during the disease course (1/7). The results of skeletal muscle biopsy in 6 patients were consistent with autophagy vacuolar myopathy. Subendocardial myocardial biopsy was performed in 3 patients, and a large amount of glycogen deposition with autophagosome formation was found in cardiomyocytes. LAMP-2 gene was detected in 6 patients, and missense mutations were found in all these patients. During the follow-up period, implantable cardioverter defibrillator implantation was performed in 1 patient because of high atrioventricular block 4 years after diagnosis, and there was no death or hospitalization for cardiovascular events in the other patients. Conclusion: The main clinical manifestations of Danon disease are cardiomyopathy, myopathy and mental retardation. Pre-excitation syndrome is a common electrocardiographic manifestation. Autophagy vacuoles can be seen in skeletal muscle and myocardial pathological biopsies. LAMP-2 gene mutation analysis is helpful in the diagnose of this disease.

The characteristics of pre-excitation syndrome concomitant with atrial tachyarrhythmia and the effect of radiofrequency ablation.

BACKGROUND: Wolff-Parkinson-White (WPW) concomitant with atrial tachyarrhythmia (ATA) has not been systemically characterized. METHODS: Detailed electroanatomical mapping of the right atrium (RA) and/or left atrium (LA) was performed using three-dimensional mapping and the accessory pathway (AP) was mapped. RESULTS: WPW syndrome with ATA was diagnosed in 11 patients (median age 60 years). The characteristic of unidirectional anterograde conduction over the AP was displayed in nine patients, six of whom were intermittent. Sustained atrial tachycardia, that is, counterclockwise atrial flutter (AFL) with a median tachycardia cycle length (TCL) of 225 (220-275) ms, was mapped in eight patients; furthermore, "figure 8" right atrial reentry was mapped with TCL 250 ms in one patient with a surgical history of ventricular septal defect repair. The remaining two patients underwent mitral annulus-dependent AT after paroxysmal atrial fibrillation (PAF) ablation and LA micro-reentry AT, respectively. In four patients, the location of the APs was left posterior. Left-lateral APs were identified in four patients. The locations of the APs in the remaining three patients were the right posterior and middle septum. All ATAs and APs were successfully ablated. After a median follow-up of 37 (15-72) months, no anterograde conduction over the AP was recorded, new onset of PAF was recorded in three patients, and all of them underwent circumferential pulmonary vein isolation. CONCLUSIONS: WPW with concomitant ATA frequently had continuous anterograde conduction over the AP with a rapid ventricular rate. Most WPWs displayed the characteristic of unidirectional anterograde conduction.

Pre-excitation syndrome presenting with acute myocardial infarction.

A male in his mid 50s, chronic smoker and hypertensive for 10 years presented with history suggestive of typical angina, electrocardiographic evidence of pre-excitation and serial elevation of cardiac biomarkers. Serial electrocardiograms showed subtle changes (axis shift, horizontal ST-segment changes) that could be presumptive of an anterior wall myocardial infarction. Speckle tracking echocardiography revealed territorial reduction of longitudinal strain corresponding to the left anterior descending artery with coronary angiography corroborating the same and underwent successful revascularisation. Exercise stress testing showed abrupt and complete disappearance of delta wave and normalisation of PR interval which indicates that the patient has low risk of developing malignant arrhythmias and sudden cardiac death.