Zachary Laksman

Exercise Testing in Asymptomatic Gene Carriers Exposes a Latent Electrical Substrate of Arrhythmogenic Right Ventricular Cardiomyopathy

OBJECTIVES The aim of this study was to determine if exercise testing could expose a latent electrical substrate of arrhythmogenic right ventricular cardiomyopathy (ARVC) in asymptomatic gene carriers. BACKGROUND Management of asymptomatic ARVC gene carriers is challenging because of variable penetrance of disease and the recognition that sudden cardiac death may be the first clinical manifestation. METHODS Exercise-induced abnormalities during exercise treadmill testing (ETT) were initially compared in 60 subjects: 30 asymptomatic ARVC gene carriers and 30 healthy controls. In phase 2 of the study, ETT results of 25 patients with ARVC with histories of sustained ventricular arrhythmia or cardiac arrest were evaluated to determine if ETT abnormalities in asymptomatic gene carriers were common to patients with a malignant electrical form of the disease. RESULTS Depolarization abnormalities during ETT were found to develop more frequently in asymptomatic gene carriers compared with healthy controls: epsilon waves appeared in 4 of 28 (14%) compared with 0 of 30 (0%) (p = 0.048), premature ventricular contractions in 17 of 30 (57%) compared with 3 of 30 (10%) (p = 0.0003), and new QRS terminal activation duration ≥ 55 ms in 7 of 22 (32%) compared with 2 of 29 (7%) (p = 0.03). Superior axis premature ventricular contractions occurred only in gene carriers. In the second phase of the study, the frequency of these abnormalities was found to be high in patients with symptomatic ARVC: new epsilon waves appeared in 3 of 18 (17%), superior axis premature ventricular contractions in 21 of 25 (84%), and new terminal activation duration ≥ 55 ms in 8 of 12 (67%). CONCLUSIONS Exercise testing exposes a latent electrical substrate in asymptomatic ARVC gene carriers that is shared by patients with ARVC with histories of ventricular arrhythmia. ETT may be useful in guiding treatment decisions, exercise prescription, and prioritizing medical surveillance in asymptomatic ARVC gene carriers.

Early repolarization is associated with symptoms in patients with type 1 and type 2 long QT syndrome

BACKGROUND Early repolarization (ER) is associated with an increased risk for death from cardiac causes. Recent evidence supports ERs role as a modifier and/or predictor of risk in many cardiac conditions. OBJECTIVE The purpose of this study was to determine the prevalence of ER among genotype-positive patients with long QT syndrome (LQTS) and evaluate its utility in predicting the risk of symptoms. METHODS ER was defined as QRS slurring and/or notching associated with ≥1-mV QRS-ST junction (J-point) elevation in at least 2 contiguous leads, excluding the anterior precordial leads. The ECG with the most prominent ER was used for analysis. Major ER was defined as ≥ 2-mm J-point elevation. Symptoms of LQTS included cardiac syncope, documented polymorphic ventricular tachycardia (VT), and resuscitated cardiac arrest. RESULTS One hundred thirteen patients (mean age 41 ± 19 years; 63 female) were reviewed, among whom 414 (mean 3.7 ± 1.5) ECGs were analyzed. Of these, 30 patients (27%) with a history of symptoms. Fifty patients (44%) had ER, and 19 patients (17%) had major ER. Patients with major ER were not different from patients without major ER with respect to age, sex, long QT type, longest QTc recorded, number of patients with QTc >500 ms, or use of beta-blockade. Univariate and independent predictors of symptom status included the presence of major ER, longest QTc recorded >500 ms, and female sex. CONCLUSION ER ≥2 mm was the strongest independent predictor of symptom status related to LQTS, along with female sex and QTc >500 ms.

Mutation Location Effect on Severity of Phenotype During Exercise Testing in Type 1 Long-QT Syndrome: Impact of Transmembrane and C-Loop Location

Targeted mutation site‐specific differences have correlated C‐loop missense mutations with worse outcomes and increased benefit of beta‐blockers in LQT1. This observation has implicated the C‐loop region as being mechanistically important in the altered response to sympathetic stimulation known to put patients with LQT1 at risk of syncope and sudden cardiac death.

Model-Based Navigation of Left and Right Ventricular Leads to Optimal Targets for Cardiac Resynchronization Therapy A Single-Center Feasibility Study

Background—Left ventricular (LV) and right ventricular pacing site characteristics have been shown to influence response to cardiac resynchronization therapy (CRT). This study aimed to determine the clinical feasibility of image-guided lead delivery using a 3-dimensional navigational model displaying both LV and right ventricular (RV) pacing targets. Serial echocardiographic measures of clinical response and procedural metrics were evaluated. Methods and Results—Thirty-one consecutive patients underwent preimplant cardiac MRI with the generation of a 3-dimensional navigational model depicting optimal segmental targets for LV and RV leads. Lead delivery was guided by the model in matched views to intraprocedural fluoroscopy. Blinded assessment of final lead tip location was performed from postprocedural cardiac computed tomography. Clinical and LV remodeling response criteria were assessed at baseline, 3 months, and 6 months using a 6-minute hall walk, quality of life questionnaire, and echocardiography. Mean age and LV ejection fraction was 66±8 years and 26±8%, respectively. LV leads were successfully delivered to a target or adjacent segment in 30 of 31 patients (97%), 68% being nonposterolateral. RV leads were delivered to a target or adjacent segment in 30 of 31 patients (97%), 26% being nonapical. Twenty-three patients (74%) met standard criteria for response (LV end-systolic volume reduction ≥15%), 18 patients (58%) for super-response (LV end-systolic volume reduction ≥30%). LV ejection fraction improved at 6 months (31±8 versus 26±8%, P=0.04). Conclusions—This study demonstrates clinical feasibility of dual cardiac resynchronization therapy lead delivery to optimal targets using a 3-dimensional navigational model. High procedural success, acceptable procedural times, and a low rate of early procedural complications were observed. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01640769.

A Detailed Description and Assessment of Outcomes of Patients With Hospital Recorded QTc Prolongation

Corrected QT (QTc) interval prolongation has been shown to be an independent predictor of mortality in many clinical settings and is a common finding in hospitalized patients. The causes and outcomes of patients with extreme QTc interval prolongation during a hospital admission are poorly described. The aim of this study was to prospectively identify patients with automated readings of QTc intervals >550 ms at 1 academic tertiary hospital. One hundred seventy-two patients with dramatic QTc interval prolongation (574 ± 53 ms) were identified (mean age 67.6 ± 15.1 years, 48% women). Most patients had underlying heart disease (60%), predominantly ischemic cardiomyopathy (43%). At lease 1 credible and presumed reversible cause associated with QTc interval prolongation was identified in 98% of patients. The most common culprits were QTc interval-prolonging medications, which were deemed most responsible in 48% of patients, with 25% of these patients taking ≥2 offending drugs. Two patients were diagnosed with congenital long-QT syndrome. Patients with electrocardiograms available before and after hospital admission demonstrated significantly lower preadmission and postdischarge QTc intervals compared with the QTc intervals recorded in the hospital. In conclusion, in-hospital mortality was high in the study population (29%), with only 4% of patients experiencing arrhythmic deaths, all of which were attributed to secondary causes.

Arrhythmogenic Right Ventricular Cardiomyopathy With Recessive Inheritance Related to a New Homozygous Desmocollin-2 Mutation

Arrhythmogenic right ventricular cardiomyopathy/dysplasia is an inherited cardiomyopathy that is transmitted in autosomal dominant and autosomal recessive forms and involves mutations in desmosomal and extradesmosomal genes. We present a case of arrhythmogenic right ventricular cardiomyopathy that cosegregates in a Lebanese family with a previously unreported desmocollin-2 mutation (c.712_714delGAT). We believe this newly described genetic variant displays autosomal recessive inheritance without the cutaneous manifestations expected in recessive genotypes, and represents the latest addition to the compendium of desmosomal mutations with pathogenic potential.

An “Irritating” Magnet Test

A 77-year-old man was referred to our institution for dual-chamber pacemaker implantation for sinus node dysfunction. His presenting rhythm was sinus bradycardia at 45 beats/min, PR interval was 230 ms, and QRS width was normal. He had no previous history of coronary artery disease or cardiovascular risk factors and had a structurally normal heart on echocardiography. Preoperative bloodwork (including electrolytes) was unremarkable and he was not receiving any antiarrhythmic agents. During device implantation, poor R-wave sensing (below 4 mV) was noted at multiple sites in the right ventricle (RV; including the apical septum, mid-septal region, and RV outflow tract) despite an appropriate current of injury pattern and slew rate >0.75 V/s at these sites. After testing a total of 10 sites in the RV, an appropriate position in the RV apex was found where the Medtronic 5076 active-fixation RV lead (Medtronic Inc., Minneapolis, MN, USA) was placed. Final RV lead parameters consisted of a sensed R wave of 9 mV, a capture threshold of 0.50 V, and an impedance of 560 . The atrial lead (Medtronic R

Evolution of a genetic diagnosis

Understanding the relationship between genotype and phenotype has become an integral part of the diagnosis and management of patients with inherited arrhythmias and cardiomyopathies. Given the existence of background noise, the majority of genetic testing results should be incorporated into clinical decision making as probabilistic, rather than deterministic, in the diagnosis and management of inherited arrhythmias. This case report captures multiple snapshots of clinical care in the evolution of a diagnosis of a single patient, highlighting the need for repeated phenotypic and genotypic assessment for both the patient and their family.

IMPACT OF EXERCISE AND RECOVERY ON EARLY REPOLARIZATION IN LONG QT SYNDROME

BACKGROUND: There are limited therapeutic options for patients with structural heart disease and refractory ventricular tachycardia (VT) who have failed standard antiarrhythmic therapy. Even after VT ablation, recurrent VT is common; furthermore many patients are not candidates for VT ablation. Oral procainamide has a potential role in treatment of refractory VT but its efficacy and safety has not been evaluated in contemporary practice among patients with implantable cardioverter-defibrillator (ICDs). METHODS: We conducted a retrospective cohort study between 2006-2013 at a tertiary referral center evaluating the use of oral procainamide in refractory VT. Patients were eligible if they had: 1) a left ventricular ejection fraction (LVEF) 40 %, 2) an ICD in place and 3) VT despite standard class-III AAD. Subjects were followed for 1 year for a primary outcome of appropriate ICD-shock or sustained VT below detection, VT ablation or heart transplantation/LVAD. The safety endpoints included adverse drug effects requiring discontinuation or exacerbation of heart failure. RESULTS: A total of 23 patients were identified. Mean age was 70 10 years and mean LVEF was 28 8%. The majority had ischemic cardiomyopathy (61%) and a secondary prevention ICD (83%). Forty-four percent had a history of VT-storm and 61% had prior VT ablation. Prior antiarrhythmic exposure included amiodarone in 87%, sotalol in 48% and mexiletine in 70%. Procainamide was introduced during hospitalization in 90% at a mean daily dose of 1821 562 mg. Recurrent appropriate ICD shock (39%) and VT storm (30%) were the most common indications. The composite primary outcome occurred in 12/23 (52%) at a median of 42 days (range 5-311). VT ablation for inefficacy occurred in 26% and recurrent ICD shock occurred in 22%. Safety endpoints occurred in 8/23 (35%) at a median of 63 days (range 5-258). Unplanned heart failure hospitalization occurred in 30% and adverse effects occurred in 17%. The overall mortality was 22% and 13% underwent transplantation/LVAD for primary heart failure. CONCLUSION: Oral procainamide has limited efficacy in highly morbid patients with refractory VT and previous failure of standard AAD. The high rate of treatment failure emphasizes the need for improved treatment options.