Diagnosis of Brugada Syndrome With a Sodium-Channel-Blocker Test: Who Should Be Tested? Who Should Not?

Intravenous infusion of sodium-channel blockers (SCB) with either ajmaline, flecainide, procainamide, or pilsicainide to unmask the ECG of Brugada syndrome is the drug challenge most commonly used for diagnostic purposes when investigating cases possibly related to inherited arrhythmia syndromes. For a patient undergoing an SCB challenge, the impact of a positive result goes well beyond its diagnostic implications. It is, therefore, appropriate to question who should undergo a SCB test to diagnose or exclude Brugada syndrome and, perhaps more importantly, who should not. We present a critical review of the benefits and drawbacks of the SCB challenge when performed in cardiac arrest survivors, patients presenting with syncope, family members of probands with confirmed Brugada syndrome, and asymptomatic patients with suspicious ECG.

Arrhythmogenic Effects of Cardiac Memory.

Cardiac memory is the term used to describe an interesting electrocardiographic phenomenon. Whenever a QRS complex is wide and abnormal, such as during ventricular pacing, the T waves will also be abnormal and will point to the opposite direction of the wide QRS. If the QRS then normalizes, such as after cessation of ventricular pacing, the T waves will normalize as well, but at a later stage. The period of cardiac memory is the phase between the sudden normalization of the QRS and the eventual and gradual return of the T waves to their baseline morphology. Cardiac memory is assumed to be an innocent electrocardiographic curiosity. However, during cardiac memory, reduction of repolarizing potassium currents increases left ventricular repolarization gradients. Therefore, when cardiac memory occurs in patients who already have a prolonged QT interval (for whatever reason), it can lead to a frank long QT syndrome with QT-related ventricular arrhythmias (torsades de pointes). These arrhythmogenic effects of cardiac memory are not generally appreciated and are reviewed here for the first time.

Polymorphic Ventricular Tachycardia: Terminology, Mechanism, Diagnosis, and Emergency Therapy.

Polymorphic ventricular tachyarrhythmias are highly lethal arrhythmias. Several types of polymorphic ventricular tachycardia have similar electrocardiographic characteristics but have different modes of therapy. In fact, medications considered the treatment of choice for one form of polymorphic ventricular tachycardia, are contraindicated for the other. Yet confusion about terminology, and thus diagnosis and therapy, continues. We present an in-depth review of the different forms of polymorphic ventricular tachycardia and propose a practical step-by-step approach for distinguishing these malignant arrhythmias.

Polymorphic ventricular tachycardia, ischaemic ventricular fibrillation, and torsade de pointes: importance of the QT and the coupling interval in the differential diagnosis.

AIMS: Distinctive types of polymorphic ventricular tachycardia (VT) respond differently to different forms of therapy. We therefore performed the present study to define the electrocardiographic characteristics of different forms of polymorphic VT. METHODS AND RESULTS: We studied 190 patients for whom the onset of 305 polymorphic VT events was available. The study group included 87 patients with coronary artery disease who had spontaneous polymorphic VT triggered by short-coupled extrasystoles in the absence of myocardial ischaemia. This group included 32 patients who had a long QT interval but nevertheless had their polymorphic VT triggered by ectopic beats with short coupling interval, a subcategory termed 'pseudo-torsade de pointes] (TdP). For comparison, we included 50 patients who had ventricular fibrillation (VF) during acute myocardial infarction ('ischaemic VF' group) and 53 patients with drug-induced TdP ('true TdP' group). The QT of patients with pseudo-TdP was (by definition) longer than that of patients with polymorphic VT and normal QT (QTc 491.4 ± 25.2 ms vs. 447.3 ± 55.6 ms, P < 0.001). However, their QT was significantly shorter than that of patients with true TdP (QTc 564.6 ± 75.6 ms, P < 0.001). Importantly, the coupling interval of the ectopic beat triggering the arrhythmia was just as short during pseudo-TdP as during polymorphic VT with normal QT (359.1 ± 38.1 ms vs. 356.6 ± 39.4 ms, P = 0.467) but was much shorter than during true TdP (581.2 ± 95.3 ms, P < 0.001). CONCLUSIONS: The coupling interval helps discriminate between polymorphic VT that occurs despite a long QT interval (pseudo-TdP) and polymorphic arrhythmias striking because of a long QT (true TdP).

Arrhythmic storm from ischemic ventricular fibrillation treated with intravenous quinidine.

We present a case who developed an acute right ventricular infarction. The leads demonstrating ST-segment elevation were different than those expected based on previous publications. We explain why this happened with the aid of 3-dimentional imaging. Our case then developed an arrhythmic storm caused by ischemic ventricular fibrillation (VF). Emergency revascularization failed and the VF-storm failed to respond to sedation, lidocaine and amiodarone but responded to intravenous quinidine.

Pulmonary Vein Isolation With Ablation Index via Single Transseptal Crossing: Critical Role of Carina Isolation.

AIM: Reconnection of the pulmonary veins (PVs) is the most common reason for the recurrence of atrial fibrillation (AF). The ablation index is a marker of ablation lesion quality that achieves high percentages of first-pass isolation and improved AF ablation results. Most operators use a double transseptal approach with confirmation of PV isolation with a circular mapping catheter. In the present study we aimed to show that an ablation index-guided procedure using a single transseptal approach and ablation catheter only would achieve adequate PV isolation while demonstrating the critical role of the carina in PV isolation. METHOD: Sixty-six (66) consecutive patients with paroxysmal AF were included. Thirty-four (34) patients underwent wide antral circumferential ablation (WACA-only) and 32 underwent WACA+ (WACA + empiric carina isolation). All procedures were performed via single transseptal approach. Pulmonary vein isolation was confirmed with the use of a circular mapping catheter in both groups. RESULTS: Compared to WACA-only, WACA+ increased the odds of PV isolation from 65% to 94% (p=0.011). In the WACA-only procedure, ablation of the carina was needed to achieve PV isolation. At the 18-month follow-up (interquartile range 15.2-20.8 months), freedom from AF was 84% for the entire cohort. CONCLUSIONS: Our study confirmed the high success rate of PV isolation using the ablation index and showed that this can be achieved via a single transseptal crossing. Our study confirmed the role of the carina in PV isolation.

Quinidine-Responsive Polymorphic Ventricular Tachycardia in Patients With Coronary Heart Disease.

BACKGROUND: Polymorphic ventricular tachycardia (VT) without QT prolongation is well described in patients without structural heart disease (mainly idiopathic ventricular fibrillation and Brugada syndrome) and in patients with acute ST-elevation myocardial infarction. METHODS: Retrospective study of patients with polymorphic VT related to coronary artery disease, but without evidence of acute myocardial ischemia. RESULTS: The authors identified 43 patients in whom polymorphic VT developed within days of an otherwise uncomplicated myocardial infarction or coronary revascularization procedure. The polymorphic VT events were invariably triggered by extrasystoles with short (364±36 ms) coupling interval. Arrhythmic storms (4-16 events of polymorphic VT deteriorating to ventricular fibrillation) occurred in 23 (53%) patients. These arrhythmic storms were always refractory to conventional antiarrhythmic therapy, including intravenous amiodarone, but invariably responded to quinidine therapy. In-hospital mortality was 17% for patients with arrhythmic storm. Patients treated with quinidine invariably survived to hospital discharge. During long-term follow-up (of 5.6±6 years; range, 1 month to 18 years), 3 (16%) of patients discharged without quinidine developed recurrent polymorphic VT. There were no recurrent arrhythmias during quinidine therapy Conclusions: Arrhythmic storm with recurrent polymorphic VT in patients with coronary disease responds to quinidine therapy when other antiarrhythmic drugs (including intravenous amiodarone) fail.

Quinidine-responsive out-of-hospital polymorphic ventricular tachycardia in patients with coronary heart disease.

AIMS: We recently reported that patients with coronary artery disease (CAD) who develop polymorphic ventricular tachycardia (VT) during the healing phase of an acute coronary event, generally fail to respond to revascularization or standard antiarrhythmic therapy but respond immediately to quinidine therapy. Here, we describe that CAD patients presenting with out-of-hospital polymorphic VT without a recent coronary event or an obvious precipitating factor, also respond uniquely to quinidine therapy. METHODS AND RESULTS: Retrospective study of patients with unheralded, mainly out-of-hospital, polymorphic VT related to CAD but without evidence of acute myocardial ischaemia. We identified 20 patients who developed polymorphic VT without precipitating factors. The polymorphic VT events were triggered by extrasystoles with short (376 ± 49 ms) coupling interval. Arrhythmic storms occurred in 70% patients. These arrhythmic storms were generally refractory to conventional antiarrhythmic therapy but invariably responded to quinidine therapy. Revascularization was antiarrhythmic in 3 patients despite the absent clinical or ECG signs of ischaemia. During long-term follow-up (range 2 months to 11 years), 3 (15%) of patients not receiving quinidine developed recurrent polymorphic VT. There were no recurrent arrhythmias during long-term quinidine therapy. CONCLUSIONS: Patients with CAD may develop polymorphic VT in the absence of obvious acute ischaemia or apparent precipitating factors, presenting as out-of-hospital polymorphic VT with high risk of arrhythmic storms that respond uniquely to quinidine therapy.

Continuous heart rhythm monitoring using mobile photoplethysmography in ambulatory patients.

BACKGROUND: Wearable devices using photo-plethysmography (PPG) can accurately detect heart beats and may be useful for heart rate measurement and diagnosis of arrhythmias such as atrial fibrillation (AF). A previous study of a new portable PPG sensor (CardiacSense) showed high accuracy in heart rate measurement and AF detection in resting patients. We report a trial done to test the same device in active ambulatory patients with diverse characteristics. METHODS: A cohort of 24 ambulatory volunteers, underwent simultaneous PPG recording and continuous electrocardiogram (ECG) recording under different environmental conditions and situations. Per study protocol, the subjects were diverse in age, BMI, hair density and skin tone. Four subjects had AF. Heart rate measurement using the PPG device was compared to measurements by ECG. RESULTS: Of 163,527 recorded ECG-detected beats in the trial, 86,929 (53.2%) were also recorded by the PPG device. Most undetected heart beats were due to motion induced noise. Correlation between ECG and PPG was high (R = 0.94, p < 0.0001), yet in subjects with AF correlation was lower (R = 0.80, p < 0.0001). A Bland-Altman analysis showed the mean difference between measurements was -0.7 ms (95% limit of agreement -93.8 to 92.2). A total of 86,217 (99.9%) of all RR measurements were reliably measured (RR difference within 100 ms). Reliability was sustained (>99.8%) in subjects of all groups including subjects with AF. CONCLUSIONS: This study showed that, in the absence of movement-related noise, the CardiacSense PPG device can reliably detect HR in a variety of situations and subjects' characteristics.

Continuous heart rate monitoring for automatic detection of atrial fibrillation with novel bio-sensing technology.

BACKGROUND: Asymptomatic atrial fibrillation [AF] is an important cause of fatal or disabling stroke. A continuous heart-rate monitoring device, comfortable enough to be worn continuously and reliable enough to detect AF, would allow for prompt initiation of anticoagulation therapy to prevent stroke. METHODS: We studied a new custom-made wearable photo-plethysmograph [PPG] wrist-watch sensor, specifically designed for continuous heart rate monitoring and incorporating contact and motion noise-filters. We tested its ability to automatically detect AF in patients undergoing elective cardioversion of AF, using simultaneously recorded electrocardiogram [ECG] as gold standard. RESULTS: A total of 18,608 consecutive R-R-interval measurements were recorded simultaneously with PPG and ECG in 20 patients, including 12,521 [67.3%] R-R-intervals during AF and 6087 [32.7%] R-R intervals during sinus rhythm. Scatter plots and Bland-Altman plots demonstrated that the PPG signals were highly correlated to the simultaneously recorded ECG [R = 0.980, p < 0.001], both during AF and during sinus rhythm. The automatic algorithm distinguished AF from sinus rhythm with a sensitivity of 100% and specificity of 93.1%. CONCLUSIONS: This PPG-based wrist-watch sensor reliably detected AF in non-ambulatory patients.

Long-term flecainide therapy in type 3 long QT syndrome.

Aims: Type 3 long QT syndrome (LQT3) is caused by gain-of-function mutations in the cardiac sodium channel gene (SCN5A). Previous reports on the long-term use of sodium channel blockers in LQT3 are sparse. The objective of the current study was to evaluate the long-term safety and efficacy of flecainide therapy in patients with LQT3 who carry the D1790G SCN5A mutation. Methods and results: The study population comprised 30 D1790G carriers who were treated with flecainide and followed for 1-215 months (mean 145 ± 54 months, median 140 months). The mean baseline (off-drug) QTc was 522 ± 45 ms, and shortened to 469 ± 36 ms with flecainide therapy, a mean decrease of 53 ms [10.1%] (P < 0.01). A QTc longer than 500 ms was evident in 53% of carriers at baseline, and only in 13% on flecainide. All carriers while being compliant with flecainide therapy had no cardiac events during an average follow up of 83 ± 73 months. Twenty carriers stopped flecainide after an average follow up of 40 ± 42 months without symptoms. Six of them (30%) had cardiac events 1-11 months after stopping flecainide. Flecainide induced the appearance of Brugada pattern in six carriers (20%, 5 males), was stopped in three and was not associated with arrhythmia. Sinus-node dysfunction was evident in six carriers (20%) and was fully corrected by flecainide in three. Conclusions: These data suggest that long-term flecainide therapy is relatively safe and effective among LQT3 patients who carry the D1790G SCN5A mutation.

New formula for defining "normal" and "prolonged" QT in patients with bundle branch block.

OBJECTIVES: To predict the QT interval in the presence of normal QRS for patients with left bundle branch block (LBBB). BACKGROUND: There is no acceptable method for simple and reliable QT correction for patients with bundle branch block (BBB). METHODS: We measured the QT interval in patients with new onset LBBB who had a recent electrocardiogram with narrow QRS for comparison. 48 patients who developed in-hospital LBBB were studied. Patients who had similar heart rate before and after LBBB were included. We used linear regression, the Bogossian method, and our new fixed QRS replacement method to evaluate the most reliable correction method. RESULTS: JTc (QTc-QRS) interval was preserved before and after LBBB (328.9 ±â€¯25.4 ms before LBBB vs. 327.3 ms post LBBB (p = 0.550). Mean predicted preLBBB QTc difference was 1.3 ms, -21.3 ms and 1.6 ms for the three methods respectively (p < 0.001 for Bogossian comparison with the other methods). Coefficients of correlation (R) between actual preLBBB QTc with predicted preLBBB QTc were 0.707, 0.683 and 0.665 respectively (p > 0.3 for R comparisons between all methods). The average absolute difference in preLBBB QTc was 15.5 ms and 16.7 ms for the regression and fixed-gender methods (p value between the two = 0.321) and 25.5 ms for the Bogossian method, which was found to be significantly underperforming. CONCLUSIONS: In patients with LBBB, replacing of the QRS duration after deriving the QTc interval with a fixed value of 88 ms for female and 95 ms for male provides a simple and reliable method for predicting the QTc before the development of LBBB.

Survival with cardiac-resynchronization therapy in mild heart failure.

BACKGROUND: The Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) showed that early intervention with cardiac-resynchronization therapy with a defibrillator (CRT-D) in patients with an electrocardiographic pattern showing left bundle-branch block was associated with a significant reduction in heart-failure events over a median follow-up of 2.4 years, as compared with defibrillator therapy alone. METHODS: We evaluated the effect of CRT-D on long-term survival in the MADIT-CRT population. Post-trial follow-up over a median period of 5.6 years was assessed among all 1691 surviving patients (phase 1) and subsequently among 854 patients who were enrolled in post-trial registries (phase 2). All reported analyses were performed on an intention-to-treat basis. RESULTS: At 7 years of follow-up after initial enrollment, the cumulative rate of death from any cause among patients with left bundle-branch block was 18% among patients randomly assigned to CRT-D, as compared with 29% among those randomly assigned to defibrillator therapy alone (adjusted hazard ratio in the CRT-D group, 0.59; 95% confidence interval [CI], 0.43 to 0.80; P<0.001). The long-term survival benefit of CRT-D in patients with left bundle-branch block did not differ significantly according to sex, cause of cardiomyopathy, or QRS duration. In contrast, CRT-D was not associated with any clinical benefit and possibly with harm in patients without left bundle-branch block (adjusted hazard ratio for death from any cause, 1.57; 95% CI, 1.03 to 2.39; P=0.04; P<0.001 for interaction of treatment with QRS morphologic findings). CONCLUSIONS: Our findings indicate that in patients with mild heart-failure symptoms, left ventricular dysfunction, and left bundle-branch block, early intervention with CRT-D was associated with a significant long-term survival benefit. (Funded by Boston Scientific; ClinicalTrials.gov numbers, NCT00180271, NCT01294449, and NCT02060110.).

Radiofrequency Ablation of Atrial Fibrillation: Nonrandomized Comparison of Circular versus Point-by-Point "Smart" Ablation for Achieving Circumferential Pulmonary Vein Isolation and Curing Arrhythmic Symptoms.

INTRODUCTION: Pulmonary vein isolation (PVI) with radiofrequency (RF) ablation is now standard care for atrial fibrillation (AF). New improvements in PVI techniques include use of catheters that measure contact-force and circular ablation catheters. These techniques have not been compared. METHODS AND RESULTS: We compared the success rate of circumferential pulmonary vein isolation (CPVI) with: (1) "point by point" RF using an irrigated tip ablation catheter with "smart touch" contact-force; (2) irrigated nMARQ circular ablation catheter in 86 patients with AF. The endpoints of the study were acute and long-term success rate of CPVI. The 2 groups had similar characteristics: Smart Touch group with 50 patients, age 62 ± 8 years, 64% male; nMARQ group with 36 patients, 75% male, age 58.7 ± 10 years. The type of AF was similar in the 2 groups: paroxysmal and persistent in 68% and 32% in the Navistar group versus 64% and 36% in the nMARQ group. Follow-up periods were similar (18.4 months vs. 19 months, P = 0.59). All the pulmonary veins were successfully isolated in both groups. However, PVI could not be achieved with the nMARQ in 2.7% of the pulmonary veins ablated and was completed with a Smart Touch. The long-term success rate was comparable in the 2 groups. CONCLUSION: The nMARQ and Smart Touch catheters give similar results in PVI of both paroxysmal and persistent AF. The procedural time was shorter with the nMARQ in paroxysmal AF. Need for crossover from nMARQ to Smart Touch occurred in 2.7% of PVs ablated.