Samy Elayi

Atrioventricular dyssynchrony from empiric device settings is common in cardiac resynchronization therapy and adversely impacts left ventricular morphology and function

Echocardiographic atrioventricular (AV) optimization after cardiac resynchronization therapy (CRT) is uncommon due to time constraints and the use of vendor‐specific device algorithms. It remains unclear whether optimization of mitral inflow velocities can still be useful. We aimed to investigate post implantation left ventricular (LV) inflow patterns to determine the incidence of AV dyssynchrony from empirically set devices.

Functional Invalidation of Putative Sudden Infant Death Syndrome–Associated Variants in the KCNH2-Encoded Kv11.1 Channel

Background: Heterologous functional validation studies of putative long-QT syndrome subtype 2–associated variants clarify their pathological potential and identify disease mechanism(s) for most variants studied. The purpose of this study is to clarify the pathological potential for rare nonsynonymous KCNH2 variants seemingly associated with sudden infant death syndrome. Methods: Genetic testing of 292 sudden infant death syndrome cases identified 9 KCNH2 variants: E90K, R181Q, A190T, G294V, R791W, P967L, R1005W, R1047L, and Q1068R. Previous studies show R181Q-, P967L-, and R1047L-Kv11.1 channels function similar to wild-type Kv11.1 channels, whereas Q1068R-Kv11.1 channels accelerate inactivation gating. We studied the biochemical and biophysical properties for E90K-, G294V-, R791W-, and R1005W-Kv11.1 channels expressed in human embryonic kidney 293 cells; examined the electronic health records of patients who were genotype positive for the sudden infant death syndrome–linked KCNH2 variants; and simulated their functional impact using computational models of the human ventricular action potential. Results: Western blot and voltage-clamping analyses of cells expressing E90K-, G294V-, R791W-, and R1005W-Kv11.1 channels demonstrated these variants express and generate peak Kv11.1 current levels similar to cells expressing wild-type-Kv11.1 channels, but R791W- and R1005W-Kv11.1 channels accelerated deactivation and activation gating, respectively. Electronic health records of patients with the sudden infant death syndrome–linked KCNH2 variants showed that the patients had median heart rate–corrected QT intervals <480 ms and none had been diagnosed with long-QT syndrome or experienced cardiac arrest. Simulating the impact of dysfunctional gating variants predicted that they have little impact on ventricular action potential duration. Conclusions: We conclude that these rare Kv11.1 missense variants are not long-QT syndrome subtype 2–causative variants and therefore do not represent the pathogenic substrate for sudden infant death syndrome in the variant-positive infants.

35% OF EMPIRIC ATRIOVENTRICULAR DELAY SETTINGS MAY BENEFIT FROM ADDITIONAL OPTIMIZATION

Vendor-specific atrioventricular (AV) delay settings in Cardiac Resynchronization Therapy (CRT) offer a convenient alternative to Echocardiographic Doppler-Guided optimization yet it is still unclear how optimized these settings are. This study investigates the effect of empiric device settings on

QT PROLONGATION IS ASSOCIATED WITH MORTALITY IN END STAGE LIVER DISEASE PATIENTS

QT prolongation is associated with increased risk of ventricular arrhythmias and sudden cardiac death. Previous studies have suggested increased prevalence of QT prolongation in end stage liver disease (ESLD) patients. We aimed to determine the prevalence of QT prolongation in a large series of

DO PATIENTS WHO MEET CLASS IIA INDICATIONS FOR CARDIAC RESYNCHRONIZATION THERAPY ATTAIN A THERAPEUTIC BENEFIT

Per the 2012 ACC guidelines, Cardiac Resynchronization Therapy (CRT) is a Class IIa recommendation for low EF patients with: 1) left bundle branch block (LBBB) pattern, QRS of 120-149 ms, and NYHA class II-IV symptoms and 2) non-LBBB pattern, QRS > 150 ms, and NYHA class III/IV symptoms, however the

CMR of LV non-compaction cardiomyopathy: association of clinical presentation and prognosis with cardiac phenotype.

Methods Fourteen patients (mean age 33.1 ± 17.6 years, 9 male) were retrospectively identified from CMR database between December 2007 and May 2010. CMR imaging included SSFP cine in standard views and late gadolinium enhancement. Quantitative analysis included left and right ventricular function, volumes, mass, LV wall motion score and non-compacted to compacted myocardium (NC/C) ratios in different segments. Number of involved LV segments and regions of maximum NC/C ratio were also recorded. Patient’s medical records were reviewed for clinical history including NYHA functional class, ECG, telemetry, Holter/event monitoring and electrophysiology studies. Non-parametric U test, logistic regression analysis and parametric T-test were used to determine statistical significance as appropriate. Results Seven patients presented with acute heart failure including one in cardiogenic shock. Three patients presented with syncope, one with documented ventricular tachycardia (VT). Mean LVEF was 36.2 ± 22.8% and mean RVEF 31.5 ± 16.7%. LVEF <50% was present in 8 patients (57.1%), RVEF <40% in 7 (50%) and both in 6 (42.8%) patients. Mean NC/C myocardium ratio was 3.7±0.8 with mean of 5.5±3.1 LV segments involved. Patients with LV dysfunction were older, more symptomatic with higher NYHA class, had more myocardial segments involvement with non-compaction, and higher NC/C ratios (Table 1). No myocardial infarction or mid-wall fibrosis was seen on late gadolinium enhancement. One patient had thrombus in the right ventricle associated with severe RV dysfunction. Four patients had non-sustained monomorphic VT. Two patients had premature ventricular complexes on