Sequential His bundle and left ventricular pacing for cardiac resynchronization.

INTRODUCTION: Fusion of left ventricular pacing with intrinsic conduction provides superior resynchronization compared to biventricular pacing. His bundle pacing (HBP) preserves intrinsic conduction and allows for constant fusion with left ventricular pacing. This study evaluated sequential His bundle and left ventricular pacing for cardiac resynchronization therapy (CRT). METHODS: In patients referred for CRT, sequential His bundle and left ventricular pacing was performed when HBP did not correct the QRS. At implant, QRS duration and area were compared between biventricular pacing and His bundle and left ventricular pacing. Devices were programmed for His and left ventricular pacing. Functional status and echocardiography were evaluated in follow up. RESULTS: Twenty-one patients, seven female, 70.7 ± 9.9 years, 57% with nonischemic cardiomyopathy were included. Baseline QRS duration was 170 ± 21 ms and was 157 ± 16 ms with HBP. Biventricular pacing resulted in a QRS duration of 141 ± 15 ms and decreased to 110 ± 14 ms with His bundle and left ventricular pacing (p < .0005). His bundle and left ventricular pacing resulted in a smaller paced QRS area (38.5 ± 22.6 µVs) compared to biventricular pacing (67.5 ± 24.0 µVs) and baseline (78.1 ± 28.1 µVs; p < .0005). Left ventricular ejection fraction increased from 27.6 ± 6.4% to 41.1 ± 12.5 (at 25 mean months, p = .001) and functional class improved from 3.1 ± 0.5 to 2.1 ± 0.8 (at mean 32 months, p < .001). CONCLUSIONS: Sequential His bundle and left ventricular pacing results in superior electrical synchrony in patients with indication for CRT when HBP does not correct the QRS and resulted in promising clinical and echocardiographic response rates.

Direct His-bundle Pacing in a Patient with a Persistent Left Superior Vena Cava.

We report a case of direct His-bundle lead placement at the time of implantable cardioverter-defibrillator insertion and atrioventricular node ablation. The patient was found to have an isolated persistent left superior vena cava, and selective His-bundle pacing was successfully achieved through the use of a steerable sheath and dedicated mapping catheter.

His Bundle Pacing: Concept to Reality.

This article summarizes the initial experience with permanent His bundle pacing, the lessons learned, and the concepts that have been developed in the subsequent decade of experience with His bundle pacing. This article also addresses the advancements in technology, which have allowed His bundle pacing to be more widely adopted and used in various clinical situations.

Hemodynamics of His Bundle Pacing.

In addition to the His bundle, numerous other sites have been evaluated as more physiologic alternatives to pacing at the right ventricular apex. Several hemodynamic studies have shown the benefit of His bundle pacing and septal pacing in comparison with right ventricular apical pacing. This article summarizes this literature and presents acute hemodynamic data in an intrapatient study examining His bundle pacing, right ventricular septal pacing, and right ventricular apical pacing.

His bundle pacing: Initial experience and lessons learned.

Direct His bundle pacing provides the most physiologic means of artificial pacing of the ventricles with a preserved His-Purkinje system and may play a role in patients with a diseased intrinsic conduction system. We describe our initial motivations and experience with permanent direct His bundle pacing and important lessons learned since that time.

Mutations in SCN10A are responsible for a large fraction of cases of Brugada syndrome.

BACKGROUND: BrS is an inherited sudden cardiac death syndrome. Less than 35% of BrS probands have genetically identified pathogenic variants. Recent evidence has implicated SCN10A, a neuronal sodium channel gene encoding Nav1.8, in the electrical function of the heart. OBJECTIVES: The purpose of this study was to test the hypothesis that SCN10A variants contribute to the development of Brugada syndrome (BrS). METHODS: Clinical analysis and direct sequencing of BrS susceptibility genes were performed for 150 probands and family members as well as >200 healthy controls. Expression and coimmunoprecipitation studies were performed to functionally characterize the putative pathogenic mutations. RESULTS: We identified 17 SCN10A mutations in 25 probands (20 male and 5 female); 23 of the 25 probands (92.0%) displayed overlapping phenotypes. SCN10A mutations were found in 16.7% of BrS probands, approaching our yield for SCN5A mutations (20.1%). Patients with BrS who had SCN10A mutations were more symptomatic and displayed significantly longer PR and QRS intervals compared with SCN10A-negative BrS probands. The majority of mutations localized to the transmembrane-spanning regions. Heterologous coexpression of wild-type (WT) SCN10A with WT-SCN5A in HEK cells caused a near doubling of sodium channel current compared with WT-SCN5A alone. In contrast, coexpression of SCN10A mutants (R14L and R1268Q) with WT-SCN5A caused a 79.4% and 84.4% reduction in sodium channel current, respectively. The coimmunoprecipitation studies provided evidence for the coassociation of Nav1.8 and Nav1.5 in the plasma membrane. CONCLUSIONS: Our study identified SCN10A as a major susceptibility gene for BrS, thus greatly enhancing our ability to genotype and risk stratify probands and family members.

ABCC9 is a novel Brugada and early repolarization syndrome susceptibility gene.

BACKGROUND: Genetic defects in KCNJ8, encoding the Kir6.1 subunit of the ATP-sensitive K(+) channel (I(K-ATP)), have previously been associated with early repolarization (ERS) and Brugada (BrS) syndromes. Here we test the hypothesis that genetic variants in ABCC9, encoding the ATP-binding cassette transporter of IK-ATP (SUR2A), are also associated with both BrS and ERS. METHODS AND RESULTS: Direct sequencing of all ERS/BrS susceptibility genes was performed on 150 probands and family members. Whole-cell and inside-out patch-clamp methods were used to characterize mutant channels expressed in TSA201-cells. Eight ABCC9 mutations were uncovered in 11 male BrS probands. Four probands, diagnosed with ERS, carried a highly-conserved mutation, V734I-ABCC9. Functional expression of the V734I variant yielded a Mg-ATP IC50 that was 5-fold that of wild-type (WT). An 18-y/o male with global ERS inherited an SCN5A-E1784K mutation from his mother, who displayed long QT intervals, and S1402C-ABCC9 mutation from his father, who displayed an ER pattern. ABCC9-S1402C likewise caused a gain of function of IK-ATP with a shift of ATP IC50 from 8.5 ± 2 mM to 13.4 ± 5 µM (p<0.05). The SCN5A mutation reduced peak INa to 39% of WT (p<0.01), shifted steady-state inactivation by -18.0 mV (p<0.01) and increased late I(Na) from 0.14% to 2.01% of peak I(Na) (p<0.01). CONCLUSION: Our study is the first to identify ABCC9 as a susceptibility gene for ERS and BrS. Our findings also suggest that a gain-of-function in I(K-ATP) when coupled with a loss-of-function in SCN5A may underlie type 3 ERS, which is associated with a severe arrhythmic phenotype.

Riata lead failure with normal electrical lead parameters and normal fluoroscopic appearance.

Recently, insulation breach of the Riata lead raised a big concern. Management of these externalized leads has been addressed by professional organizations. However, what to do in patients with Riata leads without manifested failure is an ongoing clinical dilemma. Here, we present two clinical scenarios where the implantable cardioverter defibrillator system failed to deliver shock therapy in spite of having a new ICD generator and "appropriately functioning leads" as revealed by lead interrogation.

Externalized Conductor Cables in QuickSite Left Ventricular Pacing Lead and Riata Right Ventricular Lead in a Single Patient: A Common Problem With Silicone Insulation.

QuickSite (St Jude Medical, Sylmar, CA, USA) is a silicone and polyurethane-insulated coronary sinus pacing lead. Riata lead (St Jude Medical, Sylmar, CA, USA) is a silicone insulated right ventricular shock lead. Recently, insulation breach of silicone based leads raised a huge concern. Fluoroscopic examination of these two leads in the same patient revealed externalization of these two leads. Same mechanism producing insulation breach of Riata lead may be involved in externalization of QuickSite LV lead as distal part of insulation is also made of silicone.

Direct His-bundle pacing: present and future.

Direct His-bundle pacing (DHBP) produces rapid sequential multisite synchronous ventricular activation and, therefore, would be an ideal alternative to right ventricular apical (RVA) pacing. In 54 patients with cardiomyopathy, ejection fraction (EF) 0.23 +/- 0.11, persistent atrial fibrillation, and normal QRS < 120 ms. DHBP was attempted. This was successful in 39 patients. In seven patients, the effect of increasing heart rate on contractility (Treppe effect) was investigated. Twelve patients who also received a RVA lead underwent cardiopulmonary testing. After a mean follow-up of 42 months, 29 patients are still alive with EF improving from 0.23 +/- 0.11 to 0.33 +/- 0.15. Functional class improved from 3.5 to 2.2. DP/dt increased at each pacing site (P < 0.05) as the heart rate increased to 60, 100, and 120 beats/min. Rise in dP/dt by DHBP pacing at 120 beats/min was at least 170 +/- mmHg/s, greater than any other site in the ventricle (P < 0.05). Cardiopulmonary testing revealed longer exercise time (RVA 255 +/- 110 s) (His 280 +/- 104 s) (P < 0.05), higher O2 uptake (RVA 15 +/- 4 mL/kg per minute) (His 16 +/- 4 mL/kg minute) (P < 0.05), and later anaerobic threshold (RVA 126 +/- 71 s) (His 145 +/- 74 s) (P < 0.05) with DHBP compared to RVA pacing. Long-term DHBP is safe and effective in humans. DHBP is associated with a superior Treppe effect and increased cardiopulmonary reserve when compared to RVA pacing.

Association of angiotensin converting enzyme gene polymorphism with tachycardia cardiomyopathy.

Despite incessant tachycardia, not all patients develop tachycardia-mediated cardiomyopathy. The cardiac renin-angiotensin system may be involved in cardiac remodelling and fibrosis. The level of angiotension-converting enzyme (ACE) in the serum is associated with a 287 bp insertion (I)/deletion (D) polymorphism in intron 16 of the ACE gene. The DD genotype is associated with increased serum ACE levels and a higher incidence of idiopathic dilated and ischemic cardiomyopathy. The objective of this study was to assess whether the ACE gene I/D polymorphism is responsible for development of tachycardia-mediated cardiomyopathy. We identified 20 consecutive patients with persistent tachycardia and cardiomyopathy who showed significant improvement in ejection fraction after rate control (group A, tachycardia cardiomyopathy group). We compared the I/D genotype frequency of group A with the gene frequency of a separate group of 20 patents who, despite rapid atrial arrhythmias had preserved left ventricular ejection fraction (group B, tachycardia without cardiomyopathy group). These two groups were then compared with 24 healthy normal volunteers (group C). After a mean follow-up of 30 months, group A patients showed improvement in ejection fraction from 20+/-7 to 43+/-9% (p<0.001). Group A had a significantly higher frequency of the DD genotype than groups B and C (p-value <0.035 and <0.009 respectively). The profile of group B patients was intermediate between normal and patients with tachycardia-mediated cardiomyopathy. I/D polymorphism of the ACE gene may account for cardiomyopathy secondary to tachycardia.