Wide Complex Arrhythmia-A Unique Presentation of an Unusual Syndrome.

The mechanisms of wide complex tachycardia can vary. We discuss the case of a wide complex tachycardia with multiple mechanisms due to a rare genetic abnormality in a 26-year-old Caucasian man with a past history of spontaneous pneumothorax and syncope.

Conduction system pacing versus conventional pacing in patients undergoing atrioventricular node ablation: Nonrandomized, on-treatment comparison.

Background: Atrioventricular node ablation (AVNA) with right ventricular or biventricular pacing (conventional pacing; CP) is an effective therapy for patients with refractory atrial fibrillation (AF). Conduction system pacing (CSP) using His bundle pacing or left bundle branch area pacing preserves ventricular synchrony. Objective: The aim of our study is to compare the clinical outcomes between CP and CSP in patients undergoing AVNA. Methods: Patients undergoing AVNA at Geisinger Health System between January 2015 and October 2020 were included in this retrospective observational study. CP or CSP was performed at the operators' discretion. Procedural, pacing parameters, and echocardiographic data were assessed. Primary outcome was the combined endpoint of time to death or heart failure hospitalization (HFH) and was analyzed using Cox proportional hazards. Secondary outcomes were individual outcomes of time to death and HFH. Results: AVNA was performed in 223 patients (CSP, 110; CP, 113). Age was 75 ± 10 years, male 52%, hypertension 67%, diabetes 25%, coronary disease 40%, and left ventricular ejection fraction (LVEF) 43% ± 15%. QRS duration increased from 103 ± 30 ms to 124 ± 20 ms (P < .01) in CSP and 119 ± 32 ms to 162 ± 24 ms in CP (P < .001). During a mean follow-up of 27 ± 19 months, LVEF significantly increased from 46.5% ± 14.2% to 51.9% ± 11.2% (P = .02) in CSP and 36.4% ± 16.1% to 39.5% ± 16% (P = .04) in CP. The primary combined endpoint of time to death or HFH was significantly reduced in CSP compared to CP (48% vs 62%; hazard ratio 0.61, 95% confidence interval 0.42-0.89, P < .01). There was no reduction in the individual secondary outcomes of time to death and HFH in the CSP group compared to CP. Conclusion: CSP is a safe and effective option for pacing in patients with AF undergoing AVNA in high-volume centers.

Clinical outcomes of conduction system pacing compared to biventricular pacing in patients requiring cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) with biventricular pacing (BVP) is well-established therapy in patients with reduced left ventricular ejection fraction (LVEF) and bundle branch block or indication for pacing. Conduction system pacing (CSP) using His-bundle pacing (HBP) or left bundle branch area pacing (LBBAP) has been shown to be a safe and more physiological alternative to BVP. OBJECTIVE: The purpose of this study was to compare the clinical outcomes between CSP and BVP among patients undergoing CRT. METHODS: This observational study included consecutive patients with LVEF ≤35% and class I or II indications for CRT who underwent successful BVP or CSP at 2 major health care systems. The primary outcome was the composite endpoint of time to death or heart failure hospitalization (HFH). Secondary outcomes included subgroup analysis in left bundle branch block as well as individual endpoints of death and HFH. RESULTS: A total of 477 patients (32% female) met inclusion criteria (BVP 219; CSP 258 [HBP 87, LBBAP 171]). Mean age was 72 ± 12 years, and mean LVEF was 26% ± 6%. Comorbidities included hypertension 70%, diabetes mellitus 45%, and coronary artery disease 52%. Paced QRS duration in CSP was significantly narrower than BVP (133 ± 21 ms vs 153 ± 24 ms; P <.001). LVEF improved in both groups during mean follow-up of 27 ± 12 months and was greater after CSP compared to BVP (39.7% ± 13% vs 33.1% ± 12%; P <.001). Primary outcome of death or HFH was significantly lower with CSP vs BVP (28.3% vs 38.4%; hazard ratio 1.52; 95% confidence interval 1.082-2.087; P = .013). CONCLUSION: CSP improved clinical outcomes compared to BVP in this large cohort of patients with indications for CRT.

Clinical outcomes of left bundle branch area pacing compared to right ventricular pacing: Results from the Geisinger-Rush Conduction System Pacing Registry.

BACKGROUND: Left bundle branch area pacing (LBBAP) has been shown to be a feasible option for patients requiring ventricular pacing. OBJECTIVE: The purpose of this study was to compare clinical outcomes between LBBAP and RVP among patients undergoing pacemaker implantation METHODS: This observational registry included patients who underwent pacemaker implantations with LBBAP or RVP for bradycardia indications between April 2018 and October 2020. The primary composite outcome included all-cause mortality, heart failure hospitalization (HFH), or upgrade to biventricular pacing. Secondary outcomes included the composite endpoint among patients with a prespecified burden of ventricular pacing and individual outcomes. RESULTS: A total of 703 patients met inclusion criteria (321 LBBAP and 382 RVP). QRS duration during LBBAP was similar to baseline (121 ± 23 ms vs 117 ± 30 ms; P = .302) and was narrower compared to RVP (121 ± 23 ms vs 156 ± 27 ms; P <.001). The primary composite outcome was significantly lower with LBBAP (10.0%) compared to RVP (23.3%) (hazard ratio [HR] 0.46; 95%T confidence interval [CI] 0.306-0.695; P <.001). Among patients with ventricular pacing burden >20%, LBBAP was associated with significant reduction in the primary outcome compared to RVP (8.4% vs 26.1%; HR 0.32; 95% CI 0.187-0.540; P <.001). LBBAP was also associated with significant reduction in mortality (7.8% vs 15%; HR 0.59; P = .03) and HFH (3.7% vs 10.5%; HR 0.38; P = .004). CONCLUSION: LBBAP resulted in improved clinical outcomes compared to RVP. Higher burden of ventricular pacing (>20%) was the primary driver of these outcome differences.

Coronary Venous Visualization During Deep Septal Lead Placement: An Unexpected Finding.

Left bundle branch area pacing has emerged as a safe and feasible alternative to conventional pacing. Acute septal injury, septal perforation, and arteriovenous fistula are potential risks of deep septal implants. Contrast drainage through the lesser cardiac veins and subsequent filling of major epicardial vessels may be benign observations noted during forceful hand injection. (Level of Difficulty: Advanced.).

Left Bundle Branch Area Pacing for Cardiac Resynchronization Therapy: Results From the International LBBAP Collaborative Study Group.

OBJECTIVES: The aim of this study was to assess the feasibility and outcomes of left bundle branch area pacing (LBBAP) in patients eligible for cardiac resynchronization therapy (CRT) in an international, multicenter, collaborative study. BACKGROUND: CRT using biventricular pacing is effective in patients with heart failure and left bundle branch block (LBBB). LBBAP has been reported as an alternative option for CRT. METHODS: LBBAP was attempted in patients with left ventricular ejection fraction (LVEF) <50% and indications for CRT or pacing. Procedural outcomes, left bundle branch capture, New York Heart Association functional class, heart failure hospitalization, echocardiographic data, and lead complications were recorded. Clinical (no heart failure hospitalization and improvement in New York Heart Association functional class) and echocardiographic responses (≥5% improvement in LVEF) were assessed. RESULTS: LBBAP was attempted in 325 patients, and CRT was successfully achieved in 277 (85%) (mean age 71 ± 12 years, 35% women, ischemic cardiomyopathy in 44%). QRS configuration at baseline was LBBB in 39% and non-LBBB in 46%. Procedure and fluoroscopy duration were 105 ± 54 and 19 ± 15 min, respectively. LBBAP threshold and R-wave amplitudes were 0.6 ± 0.3 V at 0.5 ms and 10.6 ± 6 mV at implantation and remained stable during mean follow-up of 6 ± 5 months. LBBAP resulted in significant QRS narrowing from 152 ± 32 to 137 ± 22 ms (p < 0.01). LVEF improved from 33 ± 10% to 44 ± 11% (p < 0.01). Clinical and echocardiographic responses were observed in 72% and 73% of patients, respectively. Baseline LBBB (odds ratio: 3.96; 95% confidence interval: 1.64 to 9.26; p < 0.01) and left ventricular end-diastolic diameter (odds ratio: 0.62; 95% confidence interval: 0.49 to 0.79; p < 0.01) were independent predictors of echocardiographic response. CONCLUSIONS: LBBAP is feasible and safe and provides an alternative option for CRT. LBBAP provides remarkably low and stable pacing thresholds and was associated with improved clinical and echocardiographic outcomes.

Prevalence and Electronic Health Record-Based Phenotype of Loss-of-Function Genetic Variants in Arrhythmogenic Right Ventricular Cardiomyopathy-Associated Genes.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with variants in desmosome genes. Secondary findings of pathogenic/likely pathogenic variants, primarily loss-of-function (LOF) variants, are recommended for clinical reporting; however, their prevalence and associated phenotype in a general clinical population are not fully characterized. METHODS: From whole-exome sequencing of 61 019 individuals in the DiscovEHR cohort, we screened for putative loss-of-function variants in PKP2, DSC2, DSG2, and DSP. We evaluated measures from prior clinical ECG and echocardiograms, manually over-read to evaluate ARVC diagnostic criteria, and performed a PheWAS (phenome-wide association study). Finally, we estimated expected penetrance using Bayesian inference. RESULTS: One hundred forty individuals (0.23%; 59±18 years old at last encounter; 33% male) had an ARVC variant (G+). None had an existing diagnosis of ARVC in the electronic health record, nor significant differences in prior ECG or echocardiogram findings compared with matched controls without variants. Several G+ individuals satisfied major repolarization (n=4) and ventricular function (n=5) criteria, but this prevalence matched controls. PheWAS showed no significant associations of other heart disease diagnoses. Combining our best genetic and disease prevalence estimates yields an estimated penetrance of 6.0%. CONCLUSIONS: The prevalence of ARVC loss-of-function variants is ≈1:435 in a general clinical population of predominantly European descent, but with limited electronic health record-based evidence of phenotypic association in our population, consistent with a low penetrance estimate. Prospective deep phenotyping and longitudinal follow-up of a large sequenced cohort is needed to determine the true clinical relevance of an incidentally identified ARVC loss-of-function variant.

The cardiomyocyte lineage is critical for optimization of stem cell therapy in a mouse model of myocardial infarction.

We recently described a murine embryonic stem cell (ESC) line engineered to express the activated Notch 4 receptor in a tetracycline (doxcycline; Dox) regulated fashion (tet-notch4 ESCs). Notch 4 induction in Flk1(+) hematopoietic and vascular progenitors from this line respecified them to a cardiovascular fate. We reasoned that these cells would be ideal for evaluating the contribution of the cardiomyocyte and vascular lineages to the functional improvement noted following stem cell transplantation in infarcted hearts. Flk-1(+) Tet-notch4 cells from d 3 embryoid bodies exposed to doxycycline (Dox(+)) were compared to uninduced (Dox(-)) Flk-1(+) cells. Mice underwent transplantation of 5 x 10(5) Dox(+) cells, Dox(-)cells, or an equal volume of serum-free medium after surgically induced myocardial infarction. The mean ejection fraction was 59 + or - 15, 46 + or - 17, and 39 + or - 13% in the Dox(+), Dox(-), and serum-free medium groups, respectively (P<0.05 for the differences among all 3 groups). Immunohistochemistry of hearts injected with Dox(+) grafts expressed myocardial and vascular markers, whereas grafts of Dox(-) cells expressed primarily vascular markers. We conclude that cardiovascular progenitors are more effective than vascular progenitors in improving function after myocardial infarction. The transplantation of appropriate cell types is critical for maximizing the benefit of cardiovascular cell therapy.-Adler, E. D., Chen, V. C., Bystrup, A., Kaplan, A. D., Giovannone, S., Briley-Saebo, K., Young, W., Kattman, S., Mani, V., Laflamme, M., Zhu, W.-Z., Fayad, Z., Keller, G. The cardiomyocyte lineage is critical for optimization of stem cell therapy in a mouse model of myocardial infarction.

In vivo detection of embryonic stem cell-derived cardiovascular progenitor cells using Cy3-labeled Gadofluorine M in murine myocardium.

OBJECTIVES: The aim of the current study is to test the ability to label and detect murine embryonic stem cell-derived cardiovascular progenitor cells (ES-CPC) with cardiac magnetic resonance (CMR) using the novel contrast agent Gadofluorine M-Cy3 (GdFM-Cy3). BACKGROUND: Cell therapy shows great promise for the treatment of cardiovascular disease. An important limitation to previous clinical studies is the inability to accurately identify transplanted cells. GdFM-Cy3 is a lipophilic paramagnetic contrast agent that contains a perfluorinated side chain and an amphiphilic character that allows for micelle formation in an aqueous solution. Previous studies reported that it is easily taken up and stored within the cytosol of mesenchymal stem cells, thereby allowing for paramagnetic cell labeling. Investigators in our laboratory have recently developed techniques for the robust generation of ES-CPC. We reasoned that GdFM-Cy3 would be a promising agent for the in vivo detection of these cells after cardiac cell transplantation. METHODS: ES-CPC were labeled with GdFM-Cy3 by incubation. In vitro studies were performed to assess the impact of GdFM-Cy3 on cell function and survival. A total of 500,000 GdFM-Cy3-labeled ES-CPC or control ES-CPC were injected into the myocardium of mice with and without myocardial infarction. Mice were imaged (9.4-T) before and over a 2-week time interval after stem cell transplantation. Mice were then euthanized, and their hearts were sectioned for fluorescence microscopy. RESULTS: In vitro studies demonstrated that GdFM-Cy3 was easily transfectable, nontoxic, stayed within cells after labeling, and could be visualized using CMR and fluorescence microscopy. In vivo studies confirmed the efficacy of the agent for the detection of cells transplanted into the hearts of mice after myocardial infarction. A correspondence between CMR and histology was observed. CONCLUSIONS: The results of the current study suggest that it is possible to identify and potentially track GdFM-Cy3-labeled ES-CPC in murine infarct models via CMR.

Injury risk behaviours among young Asian New Zealanders: a national survey of secondary school students.

OBJECTIVE: To investigate injury risk behaviours among young Asian New Zealanders. METHOD: Secondary analysis of data from Youth2000, a nationwide cross-sectional youth health survey conducted in 2001 in a random sample of New Zealand (NZ) secondary schools using a multimedia, computer-assisted, self-administered interview. Of the 9,567 survey participants (aged 12 to 18 years), this study was restricted to students who identified with an 'Asian' ethnic category (n=922). RESULTS: Many young Asian New Zealanders report engaging in injury risk behaviours, including: not using helmets when cycling; dangerous drink and drug driving; and being intentionally physically harmed by others. NZ-born Asian students are more likely than overseas-born Asian students to report most of these risky behaviours. Chinese and Indian students are less likely to engage in most of these behaviours than their NZ European peers. CONCLUSION: While young Asian New Zealanders are a relatively healthy population, many engage in well-recognised injury risk behaviours. The lower levels of these risky behaviours in Indian and Chinese students compared with NZ European students, and the positive dose-response effect seen in relation to duration of residence in NZ, are likely to be due to the effect of acculturation. IMPLICATIONS: Injury prevention strategies for young people in NZ need to specifically consider the diversity, context and specific risk profiles of young Asian New Zealanders. Health promotion efforts for this group should target the use of safety equipment and risky driving behaviours and consider traditional cultural practices that may be protective.

Depression in older Chinese migrants to Auckland.

OBJECTIVE: This study was conducted to identify risk factors for depressive symptomatology among older Chinese migrants. METHOD: One hundred and sixty-two Chinese migrants aged 55 years or older, living in the community and recruited via Chinese community organizations and general practitioners, were interviewed using a Chinese version of the Geriatric Depression Scale and measures of stressful life events, morbid conditions, self-rated health, acculturation, social support and service utilization. RESULT: Twenty-six percent of participants met the criteria for depressive symptomatology. No recent migrants showed symptoms of depression. Multiple logistic regression analysis showed that lower emotional support, greater number of visits to a doctor, difficulties in accessing health services and low New Zealand cultural orientation increased the risk of showing symptoms of depression. CONCLUSION: Significant numbers of older Chinese migrants appear to be depressed or at risk for depression and, while participants with depressive symptoms consulted general practitioners more than their counterparts without such symptoms, they reported greater difficulty in accessing health services. The findings point to the need for further epidemiological study of this growing sector of the population and investigation of the nature of its engagement with health services. Social support and aspects of acculturation may play a significant role in preventing depression. This also requires further investigation.