Decremental properties of a concealed nodoventricular pathway.

INTRODUCTION: The decremental properties of the nodoventricular pathway (NVP) are uncertain. METHODS AND RESULTS: During short RP supraventricular tachycardia, a His-refractory premature ventricular contraction (PVC) consistently terminated the tachycardia without atrial capture immediately after the PVC. Whereas a slightly earlier PVC failed to reset the subsequent His but terminated the tachycardia without atrial capture one cycle later. CONCLUSION: These observations are diagnostic of slow-fast atrioventricular nodal reentrant tachycardia (AVNRT) with a bystander concealed-NVP and can be explained by decremental properties in the NVP itself; greater prematurity of the PVC resulted in more decremental conduction over the NVP, causing the AVNRT termination one cycle later.

Acute alcohol exposure and electrocardiographic changes: Finding from the HOLIDAY trial.

BACKGROUND: Alcohol consumption is associated with a higher increased risk of atrial fibrillation (AF), but the acute effects on cardiac electrophysiology in humans remain poorly understood. The HOw ALcohol InDuces Atrial TachYarrhythmias (HOLIDAY) Trial revealed that alcohol shortened pulmonary vein atrial effective refractory periods, but more global electrophysiologic changes gleaned from the surface ECG have not yet been reported. METHODS: This was a secondary analysis of the HOLIDAY Trial. During AF ablation procedures, 100 adults were randomized to intravenous alcohol titrated to 0.08% blood alcohol concentration versus a volume and osmolarity-matched, masked, placebo. Intervals measured from 12­lead ECGs were compared between pre infusion and at infusion steady state (20 min). RESULTS: The average age was 60 years and 11% were female. No significant differences in the P-wave duration, PR, QRS or QT intervals, were present between alcohol and placebo arms. However, infusion of alcohol was associated with a statistically significant relative shortening of the JT interval (r: -14.73, p = 0.048) after multivariable adjustment. CONCLUSION: Acute exposure to alcohol was associated with a relative reduction in the JT interval, reflecting shortening of ventricular repolarization. These acute changes may reflect a more global shortening of refractoriness, suggesting immediate proarrhythmic effects pertinent to the atria and ventricles.

A Clinical Diagnostic Test for Calcium Release Deficiency Syndrome.

Importance: Sudden death and cardiac arrest frequently occur without explanation, even after a thorough clinical evaluation. Calcium release deficiency syndrome (CRDS), a life-threatening genetic arrhythmia syndrome, is undetectable with standard testing and leads to unexplained cardiac arrest. Objective: To explore the cardiac repolarization response on an electrocardiogram after brief tachycardia and a pause as a clinical diagnostic test for CRDS. Design, Setting, and Participants: An international, multicenter, case-control study including individual cases of CRDS, 3 patient control groups (individuals with suspected supraventricular tachycardia; survivors of unexplained cardiac arrest [UCA]; and individuals with genotype-positive catecholaminergic polymorphic ventricular tachycardia [CPVT]), and genetic mouse models (CRDS, wild type, and CPVT were used to define the cellular mechanism) conducted at 10 centers in 7 countries. Patient tracings were recorded between June 2005 and December 2023, and the analyses were performed from April 2023 to December 2023. Intervention: Brief tachycardia and a subsequent pause (either spontaneous or mediated through cardiac pacing). Main Outcomes and Measures: Change in QT interval and change in T-wave amplitude (defined as the difference between their absolute values on the postpause sinus beat and the last beat prior to tachycardia). Results: Among 10 case patients with CRDS, 45 control patients with suspected supraventricular tachycardia, 10 control patients who experienced UCA, and 3 control patients with genotype-positive CPVT, the median change in T-wave amplitude on the postpause sinus beat (after brief ventricular tachycardia at ≥150 beats/min) was higher in patients with CRDS (P < .001). The smallest change in T-wave amplitude was 0.250 mV for a CRDS case patient compared with the largest change in T-wave amplitude of 0.160 mV for a control patient, indicating 100% discrimination. Although the median change in QT interval was longer in CRDS cases (P = .002), an overlap between the cases and controls was present. The genetic mouse models recapitulated the findings observed in humans and suggested the repolarization response was secondary to a pathologically large systolic release of calcium from the sarcoplasmic reticulum. Conclusions and Relevance: There is a unique repolarization response on an electrocardiogram after provocation with brief tachycardia and a subsequent pause in CRDS cases and mouse models, which is absent from the controls. If these findings are confirmed in larger studies, this easy to perform maneuver may serve as an effective clinical diagnostic test for CRDS and become an important part of the evaluation of cardiac arrest.

A case series of very slow atrioventricular nodal reentrant tachycardia resembling junctional tachycardia.

INTRODUCTION: The surface electrocardiography of typical atrioventricular nodal reentrant tachycardia (AVNRT) shows simultaneous ventricular-atrial (RP) activation with pseudo R' in V1 and typical heart rates ranging from 150 to 220/min. Slower rates are suspicious for junctional tachycardia (JT). However, occasionally we encounter typical AVNRT with slow ventricular rates. We describe a series of typical AVNRT cases with heart rates under 110/min. METHODS: A total of 1972 patients with AVNRT who underwent slow pathway ablation were analyzed. Typical AVNRT was diagnosed when; (1) evidence of dual atrioventricular nodal conduction, (2) tachycardia initiation by atrial drive train with atrial-His-atrial response, (3) short septal ventriculoatrial time, and (4) ventricular-atrial-ventricular (V-A-V) response to ventricular overdrive (VOD) pacing with corrected post pacing interval-tachycardia cycle length (cPPI-TCL) > 110 ms. JT was excluded by either termination or advancement of tachycardia by atrial extrastimuli (AES) or atrial overdrive (AOD) pacing. RESULTS: We found 11 patients (age 20-78 years old, six female) who met the above-mentioned criteria. The TCL ranged from 560 to 782 ms. Except for one patient showing tachycardia termination, all patients demonstrated a V-A-V response and cPPI-TCL over 110 ms with VOD. AES or AOD pacing successfully excluded JT by either advancing the tachycardia in 10 patients or by tachycardia termination in one patient. Slow pathway was successfully ablated, and tachycardia was not inducible in all patients. CONCLUSIONS: This case series describes patients with typical AVNRT with slow ventricular rate (less than 110/min) who may mimic JT. We emphasize the importance of using pacing maneuvers to exclude JT.

Acute Consumption of Alcohol and Discrete Atrial Fibrillation Events.

BACKGROUND: Patients' self-reports suggest that acute alcohol consumption may trigger a discrete atrial fibrillation (AF) event. OBJECTIVE: To objectively ascertain whether alcohol consumption heightens risk for an AF episode. DESIGN: A prospective, case-crossover analysis. SETTING: Ambulatory persons in their natural environments. PARTICIPANTS: Consenting patients with paroxysmal AF. MEASUREMENTS: Participants were fitted with a continuous electrocardiogram (ECG) monitor and an ankle-worn transdermal ethanol sensor for 4 weeks. Real-time documentation of each alcoholic drink consumed was self-recorded using a button on the ECG recording device. Fingerstick blood tests for phosphatidylethanol (PEth) were used to corroborate ascertainments of drinking events. RESULTS: Of 100 participants (mean age, 64 years [SD, 15]; 79% male; 85% White), 56 had at least 1 episode of AF. Results of PEth testing correlated with the number of real-time recorded drinks and with events detected by the transdermal alcohol sensor. An AF episode was associated with 2-fold higher odds of 1 alcoholic drink (odds ratio [OR], 2.02 [95% CI, 1.38 to 3.17]) and greater than 3-fold higher odds of at least 2 drinks (OR, 3.58 [CI, 1.63 to 7.89]) in the preceding 4 hours. Episodes of AF were also associated with higher odds of peak blood alcohol concentration (OR, 1.38 [CI, 1.04 to 1.83] per 0.1% increase in blood alcohol concentration) and the total area under the curve of alcohol exposure (OR, 1.14 [CI, 1.06 to 1.22] per 4.7% increase in alcohol exposure) inferred from the transdermal ethanol sensor in the preceding 12 hours. LIMITATION: Confounding by other time-varying exposures that may accompany alcohol consumption cannot be excluded, and the findings from the current study of patients with AF consuming alcohol may not apply to the general population. CONCLUSION: Individual AF episodes were associated with higher odds of recent alcohol consumption, providing objective evidence that a modifiable behavior may influence the probability that a discrete AF event will occur. PRIMARY FUNDING SOURCE: National Institute on Alcohol Abuse and Alcoholism.

An International Multicenter Evaluation of Type 5 Long QT Syndrome: A Low Penetrant Primary Arrhythmic Condition.

BACKGROUND: Insight into type 5 long QT syndrome (LQT5) has been limited to case reports and small family series. Improved understanding of the clinical phenotype and genetic features associated with rare KCNE1 variants implicated in LQT5 was sought through an international multicenter collaboration. METHODS: Patients with either presumed autosomal dominant LQT5 (N = 229) or the recessive Type 2 Jervell and Lange-Nielsen syndrome (N = 19) were enrolled from 22 genetic arrhythmia clinics and 4 registries from 9 countries. KCNE1 variants were evaluated for ECG penetrance (defined as QTc >460 ms on presenting ECG) and genotype-phenotype segregation. Multivariable Cox regression was used to compare the associations between clinical and genetic variables with a composite primary outcome of definite arrhythmic events, including appropriate implantable cardioverter-defibrillator shocks, aborted cardiac arrest, and sudden cardiac death. RESULTS: A total of 32 distinct KCNE1 rare variants were identified in 89 probands and 140 genotype positive family members with presumed LQT5 and an additional 19 Type 2 Jervell and Lange-Nielsen syndrome patients. Among presumed LQT5 patients, the mean QTc on presenting ECG was significantly longer in probands (476.9±38.6 ms) compared with genotype positive family members (441.8±30.9 ms, P<0.001). ECG penetrance for heterozygous genotype positive family members was 20.7% (29/140). A definite arrhythmic event was experienced in 16.9% (15/89) of heterozygous probands in comparison with 1.4% (2/140) of family members (adjusted hazard ratio [HR] 11.6 [95% CI, 2.6-52.2]; P=0.001). Event incidence did not differ significantly for Type 2 Jervell and Lange-Nielsen syndrome patients relative to the overall heterozygous cohort (10.5% [2/19]; HR 1.7 [95% CI, 0.3-10.8], P=0.590). The cumulative prevalence of the 32 KCNE1 variants in the Genome Aggregation Database, which is a human database of exome and genome sequencing data from now over 140 000 individuals, was 238-fold greater than the anticipated prevalence of all LQT5 combined (0.238% vs 0.001%). CONCLUSIONS: The present study suggests that putative/confirmed loss-of-function KCNE1 variants predispose to QT prolongation, however, the low ECG penetrance observed suggests they do not manifest clinically in the majority of individuals, aligning with the mild phenotype observed for Type 2 Jervell and Lange-Nielsen syndrome patients.

An International Multicenter Evaluation of Inheritance Patterns, Arrhythmic Risks, and Underlying Mechanisms of CASQ2-Catecholaminergic Polymorphic Ventricular Tachycardia.

BACKGROUND: Genetic variants in calsequestrin-2 (CASQ2) cause an autosomal recessive form of catecholaminergic polymorphic ventricular tachycardia (CPVT), although isolated reports have identified arrhythmic phenotypes among heterozygotes. Improved insight into the inheritance patterns, arrhythmic risks, and molecular mechanisms of CASQ2-CPVT was sought through an international multicenter collaboration. METHODS: Genotype-phenotype segregation in CASQ2-CPVT families was assessed, and the impact of genotype on arrhythmic risk was evaluated using Cox regression models. Putative dominant CASQ2 missense variants and the established recessive CASQ2-p.R33Q variant were evaluated using oligomerization assays and their locations mapped to a recent CASQ2 filament structure. RESULTS: A total of 112 individuals, including 36 CPVT probands (24 homozygotes/compound heterozygotes and 12 heterozygotes) and 76 family members possessing at least 1 presumed pathogenic CASQ2 variant, were identified. Among CASQ2 homozygotes and compound heterozygotes, clinical penetrance was 97.1% and 26 of 34 (76.5%) individuals had experienced a potentially fatal arrhythmic event with a median age of onset of 7 years (95% CI, 6-11). Fifty-one of 66 CASQ2 heterozygous family members had undergone clinical evaluation, and 17 of 51 (33.3%) met diagnostic criteria for CPVT. Relative to CASQ2 heterozygotes, CASQ2 homozygote/compound heterozygote genotype status in probands was associated with a 3.2-fold (95% CI, 1.3-8.0; P=0.013) increased hazard of a composite of cardiac syncope, aborted cardiac arrest, and sudden cardiac death, but a 38.8-fold (95% CI, 5.6-269.1; P<0.001) increased hazard in genotype-positive family members. In vitro turbidity assays revealed that p.R33Q and all 6 candidate dominant CASQ2 missense variants evaluated exhibited filamentation defects, but only p.R33Q convincingly failed to dimerize. Structural analysis revealed that 3 of these 6 putative dominant negative missense variants localized to an electronegative pocket considered critical for back-to-back binding of dimers. CONCLUSIONS: This international multicenter study of CASQ2-CPVT redefines its heritability and confirms that pathogenic heterozygous CASQ2 variants may manifest with a CPVT phenotype, indicating a need to clinically screen these individuals. A dominant mode of inheritance appears intrinsic to certain missense variants because of their location and function within the CASQ2 filament structure.

Electrophysiologic approach to diagnosis and ablation of patients with permanent junctional reciprocating tachycardia associated with complex anatomy and/or physiology.

INTRODUCTION: Permanent junctional reciprocating tachycardia (PJRT) is a rare supraventricular tachycardia (SVT), typically involving a single decremental posteroseptal accessory pathway (AP). METHODS: Four patients with long RP SVT underwent electrophysiology (EP) study and ablation. The cases were reviewed. RESULTS: Case 1 recurred despite 3 prior ablations at the site of earliest retrograde atrial activation during orthodromic reciprocating tachycardia (ORT). Mapping during a repeat EP study demonstrated a prepotential in the coronary sinus (CS). Ablation over the earliest atrial activation in the CS resulted in dissociation of the potential from the atrium during sinus rhythm. The potential was traced back to the CS os and ablated. Case 2 underwent successful ablation at 6 o'clock on the mitral annulus (MA). ORT recurred and successful ablation was performed at 1 o'clock on the MA. Case 3 had tachycardia with variation in both V-A and A-H intervals which precluded the use of usual maneuvers so we used simultaneous atrial and ventricular pacing and introduced a premature atrial contraction with a closely coupled premature ventricular contraction. Case 4 had had two prior atrial fibrillation ablations with continued SVT over a decremental atrioventricular bypass tract that was successfully ablated at 5 o'clock on the tricuspid annulus. A second SVT consistent with a concealed nodoventricular pathway was successfully ablated at the right inferior extension of the AV nodal slow pathway. CONCLUSION: We describe challenging cases of PJRT by virtue of complex anatomy, diagnostic features, and multiple arrhythmia mechanisms.

Variants of accessory pathways.

Variant accessory pathways include atriofascicular, nodofascicular, nodoventricular, atrio-Hisian, and fasciculoventricular pathways. Atriofascicular pathways are the most common with others occurring rarely. The anatomical descriptions, electrocardiographic findings, electrophysiologic findings, and clincial manifestations are discussed.

Atrial arrhythmias in patients with arrhythmogenic right ventricular cardiomyopathy: Prevalence, echocardiographic predictors, and treatment.

INTRODUCTION: The clinical role of atrial arrhythmias (AA) in arrhythmogenic right ventricular cardiomyopathy (ARVC) and the echocardiographic variables that predict them are not well defined. We describe the prevalence, types, echocardiographic predictors, and management of AA in patients with ARVC. METHODS: We retrospectively evaluated medical records of 117 patients with definite ARVC (2010 Task Force Criteria) from two tertiary care centers. We identified those patients with sustained AA (>30 seconds), including atrial fibrillation (AF), atrial flutter (AFL), and atrial tachycardia (AT). We collected demographic, genetic, and clinical data. The median follow-up was 3.4 years (interquartile range = 2.0-5.7). RESULTS: Total 26 patients (22%) had one or more types of AA: AF (n = 19), AFL (n = 9), and AT (n = 8). We performed genetic testing on 84 patients with ARVC (71.8%). Two patients with AA (8%) had peripheral emboli, and one patient (4%) suffered inappropriate implantable cardioverter-defibrillator shock. We performed catheter ablation of AA in eight patients (31%), with no procedural complications. Right atrial area and left atrial volume index were independently associated with increased odds of AA; odds ratio (OR), 1.1 (95% confidence interval [CI]:1.02-1.16) (P = .01) and OR, 1.1 (95% CI:1.03-1.15) (P = .003), respectively. An increase in tricuspid annular plane peak systolic excursion was independently associated with reduced odds; OR, 0.3 (95% CI: 0.1-0.94) (P = .003). CONCLUSIONS: Atrial arrhythmias (AA) are common in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). Inappropriate shocks and systemic emboli may be associated with AA. Atrial size and right ventricular dysfunction may help identify patients with ARVC at increased odds of AA.

Concealed Accessory Pathways with a Single Ventricular and Two Discrete Atrial Insertion Sites.

BACKGROUND: Atrioventricular reciprocating tachycardia (AVRT) utilizing a concealed accessory pathway is common. It is well appreciated that some patients may have multiple accessory pathways with separate atrial and ventricular insertion sites. METHODS: We present three cases of AVRT utilizing concealed pathways with evidence that each utilizing a single ventricular insertion and two discrete atrial insertion sites. RESULTS: In case one, two discrete atrial insertion sites were mapped in two separate procedures, and only during the second ablation was the Kent potential identified. Ablation of the Kent potential at this site remote from the two atrial insertion sites resulted in the termination of the retrograde conduction in both pathways. Case two presented with supraventricular tachycardia (SVT) with alternating eccentric atrial activation patterns without alteration in the tachycardia cycle length. The two distinct atrial insertion sites during orthodromic AVRT and ventricular pacing were targeted and each of the two atrial insertion sites were successfully mapped and ablated. In case three, retrograde decremental conduction utilizing both atrial insertion sites was identified prior to ablation. After mapping and ablation of the first discrete atrial insertion site, tachycardia persisted utilizing the second atrial insertion site. Only after ablation of the second atrial insertion site was SVT noninducible, and VA conduction was no longer present. CONCLUSIONS: Concealed retrograde accessory pathways with discrete atrial insertion sites may have a common ventricular insertion site. Identification and ablation of the ventricular insertion site or the separate discrete atrial insertion sites result in successful treatment.

The QT Interval as a Noninvasive Marker of Atrial Refractoriness.

BACKGROUND: Atrial refractoriness may be an important determinant of atrial fibrillation (AF) risk, but its measurement is not clinically accessible. Because the QT interval predicts incident AF and the atrium and ventricle share repolarizing ion currents, we investigated the association between an individual's QT interval and atrial effective refractory period (AERP). METHODS: In paroxysmal AF patients presenting for catheter ablation, the QT interval was measured from the surface 12-lead electrocardiogram. The AERP was defined as the longest S1-S2 coupling interval without atrial capture using a 600-ms drive cycle length. RESULTS: In 28 patients, there was a positive correlation between QTc and mean AERP. After multivariate adjustment, a 1-ms increase in QTc predicted a 0.70-ms increase in AERP. CONCLUSIONS: The QTc interval reflects the AERP, suggesting that the QTc interval may be used as a marker of atrial refractoriness relevant to assessing AF risk and mechanism-specific therapeutic strategies.

Catecholaminergic Polymorphic Ventricular Tachycardia with QT Prolongation.

The QT interval in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) is typically normal. However, CPVT patients are sometimes misdiagnosed as concealed long QT syndrome (LQTS), because patients with LQTS also manifest with syncope or sudden death following periods of exertion or extreme emotion. We report a CPVT patient with a pathogenic RyR2 mutation associated with a marked QT prolongation, which normalized after flecainide therapy.

The Effect of Direct Current Stimulation versus T-Wave Shock on Defibrillation Threshold Testing.

INTRODUCTION: There are several methods to induce ventricular fibrillation (VF) during defibrillation threshold (DFT) testing. Delivering a shock at a critical time during the T wave (T-shock) is the conventional approach, while delivering a constant direct current voltage (DC stim) from the implantable cardioverter defibrillator is an alternative method. Only a few reports compare VF induction methods. The purpose of this study was to evaluate the effects and safety of DC stim versus T-shock. METHODS: We retrospectively investigated 414 consecutive patients undergoing DFT testing. We compared the two groups (DC stim and T-shock) with respect to clinical characteristics, electrocardiogram (ECG) changes, and complications. RESULTS: Ventricular arrhythmia, including ventricular tachycardia (VT) and VF, was induced by DC stim in 93 patients or T-shock in 321 patients. No more than three attempts were performed during one procedure. There was no significant difference in the baseline ECG, induced tachycardia cycle length (TCL), or complications between the two groups. However, the induced TCL was significantly shorter than the clinical TCL regardless of induction method (P = 0.001). Five patients suffered major complications (i.e., electromechanical dissociation or incessant VT). A history of atrial fibrillation was significantly greater in patients with major complications than the others (80% vs 24%, P = 0.004), and was an independent predictor on multivariate analysis. CONCLUSIONS: There is no significant difference in induced TCL or complications between the DC stim and T-shock. The induced TCL is significantly shorter than clinical TCL regardless of induction method.

Presence of septal Q waves in a patient with WPW and manifest preexcitation.

Wolff-Parkinson-White syndrome (WPW) is characteristically diagnosed by the presence of a short PR interval, a delta wave, and a wide QRS wave on the surface ECG. In the absence of these clear criteria, absent septal Q waves have been used as additional evidence suggestive of subtle preexcitation. We report a patient with WPW and manifest anteroseptal (AS) accessory pathway who had prominent septal Q waves on the surface ECG. This case highlights that physicians should be careful not to dismiss preexcitation in the presence of septal Q waves.

Coupling interval dispersion and body mass index are independent predictors of idiopathic premature ventricular complex-induced cardiomyopathy.

INTRODUCTION: Patients with frequent premature ventricular complexes (PVCs) might be at risk for the developing or exacerbation of left ventricular (LV) dysfunction. However, some patients with a high-PVC burden do not develop cardiomyopathy, while other patients with low-PVC burden can develop cardiomyopathy. The purpose of this study was to evaluate the positive predictors of idiopathic PVCs-induced cardiomyopathy. METHODS AND RESULTS: We investigated 214 patients undergoing successful ablation of PVCs who had no other causes of cardiomyopathy. We divided the study cohort into 2 groups: ejection fraction (EF) ≥ 50% (normal LV) and EF < 50% (LV dysfunction). We analyzed the clinical characteristics, including the electrocardiogram and findings at electrophysiology study. Among these patients, 51 (24%) had reduced LVEF and 163 (76%) had normal LV function. Patients with LV dysfunction had significantly longer coupling interval (CI) dispersion (maximum-CI-minimum-CI) and had significantly higher PVC burden compared to those with normal LV function (CI-dispersion: 115 ± 25 milliseconds vs. 94 ± 19 milliseconds; P < 0.001; PVC burden: 19% vs. 15%; P = 0.04). Furthermore, patients with LV dysfunction had significantly higher body mass index (BMI) compared to those with normal LV function (BMI > 30 kg/m(2) ; 37% vs. 13%; P = 0.001). Logistic regression analysis showed that CI-dispersion, PVC burden, and BMI (>30 kg/m(2) ) are independent predictors of PVC-induced cardiomyopathy. CONCLUSIONS: In addition to the PVC burden, the CI-dispersion and BMI are associated with PVC-induced cardiomyopathy.