Ablation for Atrial Fibrillation in Patients With Rare Pathogenic Variants in Cardiomyopathy and Arrhythmia Genes.

BACKGROUND: Patients with rare, pathogenic cardiomyopathy (CM) and arrhythmia variants can present with atrial fibrillation (AF). The efficacy of AF ablation in these patients is unknown. OBJECTIVE: This study tested the hypotheses that: 1) patients with a pathogenic variant in any CM or arrhythmia gene have increased recurrence following AF ablation; and 2) patients with a pathogenic variant associated with a specific gene group (arrhythmogenic left ventricular CM [ALVC], arrhythmogenic right ventricular CM, dilated CM, hypertrophic CM, or a channelopathy) have increased recurrence. METHODS: We performed a prospective, observational, cohort study of patients who underwent AF catheter ablation and whole exome sequencing. The primary outcome measure was ≥30 seconds of any atrial tachyarrhythmia that occurred after a 90-day blanking period. RESULTS: Among 1,366 participants, 109 (8.0%) had a pathogenic or likely pathogenic (P/LP) variant in a CM or arrhythmia gene. In multivariable analysis, the presence of a P/LP variant in any gene was not significantly associated with recurrence (HR 1.15; 95% CI 0.84-1.60; P = 0.53). P/LP variants in the ALVC gene group, predominantly LMNA, were associated with increased recurrence (n = 10; HR 3.75; 95% CI 1.84-7.63; P < 0.001), compared with those in the arrhythmogenic right ventricular CM, dilated CM, hypertrophic CM, and channelopathy gene groups. Participants with P/LP TTN variants (n = 46) had no difference in recurrence compared with genotype-negative-controls (HR 0.93; 95% CI 0.54-1.59; P = 0.78). CONCLUSIONS: Our results support the use of AF ablation for most patients with rare pathogenic CM or arrhythmia variants, including TTN. However, patients with ALVC variants, such as LMNA, may be at a significantly higher risk for arrhythmia recurrence.

The role of comprehensive stress cardiac MRI in autoimmune rheumatic disease: A review.

Cardiovascular disease is the leading cause of morbidity and mortality in patients with autoimmune rheumatic diseases. Much of this may be attributed to systemic inflammation resulting in coronary atherosclerosis and myocarditis. Cardiac magnetic resonance imaging is the gold standard for the evaluation of cardiac structure and function, including tissue characterization, which allows for detection of myocardial edema, inflammation, and fibrosis. Advances in parametric mapping and coronary flow reserve measurement techniques have the potential to change the diagnosis, risk stratification, and management of patients with autoimmune rheumatic diseases. We provide an overview of the current evidence and suggest potential future roles for the use of comprehensive cardiac magnetic resonance in patients with autoimmune rheumatic diseases in the field of cardio-rheumatology.

Recurrence After Atrial Fibrillation Ablation and Investigational Biomarkers of Cardiac Remodeling.

BACKGROUND: Recurrence after atrial fibrillation (AF) ablation remains common. We evaluated the association between recurrence and levels of biomarkers of cardiac remodeling, and their ability to improve recurrence prediction when added to a clinical prediction model. METHODS AND RESULTS: Blood samples collected before de novo catheter ablation were analyzed. Levels of bone morphogenetic protein-10, angiopoietin-2, fibroblast growth factor-23, insulin-like growth factor-binding protein-7, myosin-binding protein C3, growth differentiation factor-15, interleukin-6, N-terminal pro-brain natriuretic peptide, and high-sensitivity troponin T were measured. Recurrence was defined as ≥30 seconds of an atrial arrhythmia 3 to 12 months postablation. Multivariable logistic regression was performed using biomarker levels along with clinical covariates: APPLE score (Age >65 years, Persistent AF, imPaired eGFR [<60 ml/min/1.73m2], LA diameter ≥43 mm, EF <50%; which includes age, left atrial diameter, left ventricular ejection fraction, persistent atrial fibrillation, and estimated glomerular filtration rate), preablation rhythm, sex, height, body mass index, presence of an implanted continuous monitor, year of ablation, and additional linear ablation. A total of 1873 participants were included. A multivariable logistic regression showed an association between recurrence and levels of angiopoietin-2 (odds ratio, 1.08 [95% CI, 1.02-1.15], P=0.007) and interleukin-6 (odds ratio, 1.02 [95% CI, 1.003-1.03]; P=0.02). The area under the receiver operating characteristic curve of a model that only contained clinical predictors was 0.711. The addition of any of the 9 studied biomarkers to the predictive model did not result in a statistically significant improvement in the area under the receiver operating characteristic curve. CONCLUSIONS: Higher angiopoietin-2 and interleukin-6 levels were associated with recurrence after atrial fibrillation ablation in multivariable modeling. However, the addition of biomarkers to a clinical prediction model did not significantly improve recurrence prediction.

Pulmonary Vein Myocardial Sleeve Length and its Association With Sex and 4q25/PITX2 Genotype.

BACKGROUND: Experimental evidence suggests genetic variation in 4q25/PITX2 modulates pulmonary vein (PV) myocardial sleeve length. Although PV sleeves are the main target of atrial fibrillation (AF) ablation, little is known about the association between different PV sleeve characteristics with ablation outcomes. OBJECTIVES: This study sought to evaluate the association between clinical and genetic (4q25) risk factors with PV sleeve length in humans, and to evaluate the association between PV sleeve length and recurrence after AF ablation. METHODS: In a prospective, observational study of patients undergoing de novo AF ablation, PV sleeve length was measured using electroanatomic voltage mapping before ablation. The sentinel 4q25 AF susceptibility single nucleotide polymorphism, rs2200733, was genotyped. The primary analysis tested the association between clinical and genetic (4q25) risk factors with PV sleeve length using a multivariable linear regression model. Covariates included age, sex, body mass index, height, and persistent AF. The association between PV sleeve length and atrial arrhythmia recurrence (>30 seconds) was tested using a multivariable Cox proportional hazards model. RESULTS: Between 2014 and 2019, 197 participants were enrolled (median age 63 years [IQR: 55 to 70 years], 133 male [67.5%]). In multivariable modeling, men were found to have PV sleeves 2.94 mm longer than women (95% CI: 0.99-4.90 mm; P < 0.001). Sixty participants (30.5%) had one 4q25 risk allele and 6 (3.1%) had 2 alleles. There was no association between 4q25 genotype and PV sleeve length. Forty-six participants (23.4%) experienced arrhythmia recurrence within 3 to 12 months, but there was no association between recurrence and PV sleeve length. CONCLUSIONS: Common genetic variation at 4q25 was not associated with PV sleeve length and PV sleeve length was not associated with ablation outcomes. Men did have longer PV sleeves than women, but more research is needed to define the potential clinical significance of this observation.

Clinical Outcomes in Patients With Bacteremia and Concomitant Left Ventricular Assist Devices and Cardiac Implantable Electronic Devices.

Infection remains a common cause of morbidity and mortality in patients with both left ventricular assist devices (LVADs) and cardiac implanted electronic devices (CIEDs) with limited data describing outcomes in patients who have both devices implanted. We performed a single-center, retrospective, observational cohort study of patients with both a transvenous CIED and LVAD who developed bacteremia. Ninety-one patients were evaluated. Eighty-one patients (89.0%) were treated medically and nine patients (9.9%) underwent surgical management. A multivariable logistic regression showed that blood culture positivity for >72 hours was associated with inpatient death, when controlled for age and management strategy (odds ratio [OR] = 3.73 [95% confidence interval {CI} = 1.34-10.4], p = 0.012). In patients who survived the initial hospitalization, the use of long-term suppressive antibiotics was not associated with the composite outcome of death or infection recurrence within 1 year, when controlled for age and management strategy (OR = 2.31 [95% CI = 0.88-2.62], p = 0.09). A Cox proportional hazards model showed that blood culture positivity for >72 hours was associated with a trend toward increased mortality in the first year, when controlled for age, management strategy, and staphylococcal infection (hazard ratio = 1.72 [95% CI = 0.88-3.37], p = 0.11). Surgical management was associated with a trend toward decreased mortality (hazard ratio = 0.23 [95% CI = 0.05-1.00], p = 0.05).

Mortality Among Patients With Early-Onset Atrial Fibrillation and Rare Variants in Cardiomyopathy and Arrhythmia Genes.

Importance: Patients with early-onset atrial fibrillation (AF) are enriched for rare variants in cardiomyopathy and arrhythmia genes. The clinical significance of these rare variants in patients with early-onset AF is unknown. Objective: To assess the association between rare variants in cardiomyopathy and arrhythmia genes detected in patients with early-onset AF and time to death. Design, Setting, and Participants: This prospective cohort study included participants with AF diagnosed before 66 years of age who underwent whole-genome sequencing through the National Heart, Lung and Blood Institute's Trans-Omics for Precision Medicine program. Participants were enrolled from November 23, 1999, to June 2, 2015. Data were analyzed from February 26 to September 19, 2021. Exposures: Rare variants identified in a panel of 145 genes that are included in cardiomyopathy and arrhythmia panels used by commercial clinical genetic testing laboratories. Main Outcomes and Measures: The primary study outcome was time to death and was adjudicated from medical records and the National Death Index. Multivariable Cox proportional hazards regression was used to evaluate the association of disease-associated variants with risk of death after adjustment for age at AF diagnosis, sex, race, body mass index, left ventricular ejection fraction, and an interaction term of age at AF diagnosis and disease-associated variant status. Results: Among 1293 participants (934 [72%] male; median age at enrollment, 56.0 years; IQR, 48.0-61.0 years), disease-associated (pathogenic or likely pathogenic) rare variants were found in 131 (10%). During a median follow-up of 9.9 years (IQR, 6.9-13.2 years), 219 participants (17%) died. In univariable analysis, disease-associated variants were associated with an increased risk of mortality (hazard ratio, [HR], 1.5; 95% CI, 1.0-2.1; P = .05); the association remained significant in multivariable modeling when adjusted for age at AF diagnosis, sex, race, body mass index, left ventricular ejection fraction, and an interaction term between disease-associated variant status and age at AF diagnosis. The interaction demonstrated that disease-associated variants were associated with a significantly higher risk of mortality compared with no disease-associated variant when AF was diagnosed at a younger age (P = .008 for interaction). Higher body mass index (per IQR: HR, 1.4; 95% CI, 1.2-1.6; P < .001) and lower left ventricular ejection fraction (per IQR: HR, 0.8; 95% CI, 0.7-0.8; P < .001) were associated with higher mortality risk. There were 73 cardiomyopathy-related deaths, 40 sudden deaths, and 10 stroke-related deaths. Mortality among patients with the most prevalent genes with disease-associated variants was 26% (10 of 38 patients) for TTN, 33% (6 of 18) for MYH7, 22% (2 of 9) for LMNA, 0% (0 of 10) for MYH6, and 0% (0 of 8) for KCNQ1. Conclusions and Relevance: The findings suggest that rare variants in cardiomyopathy and arrhythmia genes may be associated with increased risk of mortality among patients with early-onset AF, especially those diagnosed at a younger age. Genetic testing may provide important prognostic information for patients with early-onset AF.

Durable pulmonary vein isolation with diffuse posterior left atrial ablation using low-flow, median power, short-duration strategy.

INTRODUCTION: To target posterior wall isolation (PWI) in atrial fibrillation (AF) ablation, diffuse ablation theoretically confers a lower risk of conduction recovery compared to box set. We sought to assess the safety and efficacy of diffuse PWI with low-flow, medium-power, and short-duration (LF-MPSD) ablation, and evaluate the durability of pulmonary vein isolation (PVI) and PWI among patients undergoing repeat ablations. METHODS: We retrospectively studied patients undergoing LF-MPSD ablation for AF (PVI + diffuse PWI) between August 2017 and December 2019. Clinical characteristics were collected. Kaplan-Meier survival analysis was performed to study AF/atrial flutter (AFL) recurrence. Ablation data were analyzed in patients who underwent a repeat AF/AFL ablation. RESULTS: Of the 463 patients undergoing LF-MPSD AF ablation (PVI alone, or PVI + diffuse PWI), 137 patients had PVI + diffuse PWI. Acute PWI with complete electrocardiogram elimination was achieved in 134 (97.8%) patients. Among the 126 patients with consistent follow-up, 38 (30.2%) patients had AF/AFL recurrence during a median duration of 14 months. Eighteen patients underwent a repeat AF/AFL ablation after PVI + diffuse PWI, and 16 (88.9%) patients had durable PVI, in contrast to 10 of 45 (23.9%) patients who had redo ablation after LF-MPSD PVI alone. Seven patients (38.9%) had durable PWI, while 11 patients had partial electrical recovery at the posterior wall. The median percentage of area without electrical activity at the posterior wall was 70.7%. Conduction block across the posterior wall was maintained in 16 (88.9%) patients. CONCLUSION: There was a high rate of PVI durability in patients undergoing diffuse PWI and PVI. Partial posterior wall electrical recovery was common but conduction block across the posterior wall was maintained in most patients.

Medical Procedure Services in Internal Medicine Residencies in the US: a Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: The number of procedures performed by internal medicine residents in the United States (US) is declining. An increasing proportion of residents do not feel confident performing essential invasive bedside procedures and, upon graduation, desire additional training. Several residency programs have utilized the medical procedure service (MPS) to address this issue. We aim to summarize the current state of evidence by systematically evaluating the effect of the MPS on resident education, comfort, and training, as well as patient safety and procedural outcomes in the US. METHODS: We conducted a systematic review of all studies reporting the use of an MPS with supervision from a board-certified physician in internal medicine residencies in the US. Database search was performed on PubMed, Embase, ERIC, and Cochrane Library from January 2000 to November 2020 for relevant studies. Quality of evidence assessment and random-effects proportion meta-analyses were performed. RESULTS: A total of nine studies reporting on 3879 procedures performed by MPS were identified. Procedures were safely performed, with a pooled complication rate of 2.1% (95% CI: 1.0-3.5) and generally successful, with a pooled success rate of 94.7% (95% CI: 90.8-97.7). The range of procedures performed by residents under MPS was 6.7-72.8 procedures per month (n = 9) compared to 4.3-64.4 procedures (n = 4) without MPS. MPS significantly increased confidence, comfort, and use of appropriate safety measures among residents. CONCLUSION: There are a limited number of published studies on MPS supervised by a board-certified physician in US internal medicine residencies. Procedures performed by MPS are generally successfully completed and safe. MPS benefits internal medicine residents training by improving competency, comfort, and confidence.

Outcomes of Pregnancy in Patients With Prior Right Ventricular Outflow Interventions.

Background The purpose of this study was to compare the incidence of pregnancy-related adverse outcomes ( PRAO ) between patients with versus without hemodynamically significant right ventricle outflow tract ( RVOT) . Methods and Results This was a retrospective cohort study of all pregnant patients with isolated RVOT lesions undergoing evaluation at the Mayo Clinic, 1990 to 2017. Hemodynamic significance was defined as ≥moderate pulmonary/conduit stenosis (≥3 m/s) and/or ≥moderate regurgitation. Patients with concomitant significant left heart disease were excluded. PRAO was defined as cardiovascular, obstetric, and/or neonatal complications occurring during the pregnancy through 6 weeks postpartum. A total of 224 pregnancies in 114 patients with RVOT lesions were identified; 38 pregnancies occurred in 24 patients with hemodynamically significant RVOT . Forty-eight (21%) pregnancies ended in spontaneous abortion. Of the 173 completed pregnancies, median gestational age at delivery was 38 (35-40) weeks and median birth weight 2965 (2065-4122) g. Seven pregnancies (4%) were complicated by cardiovascular events, 14 (8%) by obstetric complications, with adverse neonatal outcomes occurring in 38 (22%). There were no maternal deaths. The incidence of spontaneous abortion and PRAO were similar in both the RVOT and hemodynamically significant RVOT groups. As an isolated condition, Tetralogy of Fallot-pulmonary atresia was associated with spontaneous abortion and neonatal complications. Conclusions The risk of cardiovascular complications was low in patients with isolated RVOT lesions, and hemodynamically significant RVOT lesions were not associated with either cardiovascular complications or PRAO . Further studies are required to explore the factors responsible for PRAO in patients with Tetralogy of Fallot-pulmonary atresia.

Prediction and Management of Recurrences after Catheter Ablation in Atrial Fibrillation and Heart Failure.

Catheter ablation is recommended in patients with symptomatic atrial fibrillation (AF) refractory to pharmacologic therapy. AF recurrence is common postablation, particularly in patients with heart failure, because of multiple structural and functional changes that can occur. Determining predictors of AF recurrence has become increasingly important. These include increased left atrial volume, termination of AF during the index ablation, electrocardiogram parameters, and serum biomarkers. Cardiac MRI can also determine the degree of scarring and left atrial sphericity, which is used in risk prediction scores. In patients with recurrence, further treatment options include pharmacologic therapy and atrioventricular nodal ablation with pacing.

Diagnostic and therapeutic value of implantable loop recorder: A tertiary care center experience.

BACKGROUND: Implantable loop recorders (ILRs) are effective in achieving symptom-rhythm correlation. However, diagnostic yield in routine clinical practice is not well established. METHODS: Patients undergoing ILR implantation between April 2010 and May 2015 were included. All devices were enrolled in remote monitoring with automatic arrhythmia detection and P sense algorithms switched "ON." Symptom-rhythm correlation was assessed and changes in management were recorded. RESULTS: A total of 312 patients (57% male, age 53 ± 22 years; median CHADS2VaSc score  =  1) were included in this study. ILRs were implanted for evaluation of syncope in 206 (66.0%), presyncope in 23 (7.4%), unexplained palpitations in 51 (16.3%), and cryptogenic stroke in 27 (8.7%) patients. ILR monitoring yielded a diagnosis that changed management strategy in 146 (46.8%) patients over a median of 12 (1-42) months. Out of 163 (52.2%) patients with symptoms during the monitoring period, 100 (61.3%) had an arrhythmia. ILR was useful in ruling out an arrhythmic cause for symptoms in 63 (38.7%) patients. ILR results led to pacemaker implantation in 23 patients (7.4% overall and 11.2% of those with syncope) after median follow-up of 3 months. A new diagnosis of atrial fibrillation was made in 38 (12.2%) patients, 11 of whom were initiated on oral anticoagulants. ILR results led to pacemaker implantation in 31 patients (9.9% overall and 19.0% of those with syncope) after median follow-up of 3 months. A new diagnosis of atrial fibrillation was made in 38 (12.2%) patients, nine of whom were initiated on oral anticoagulants. Overall, ILR led to a change in management in 47% patients with a number needed to implant of 2.1 to change management. CONCLUSION: ILR monitoring is effective in achieving symptom-rhythm correlation and results in changes in management in nearly half of implanted patients. Additional studies are needed to evaluate cost efficacy of ILR and the optimal monitoring duration.

A systematic analysis of UK cancer research funding by gender of primary investigator.

OBJECTIVES: To categorically describe cancer research funding in the UK by gender of primary investigator (PIs). DESIGN: Systematic analysis of all open-access data. METHODS: Data about public and philanthropic cancer research funding awarded to UK institutions between 2000 and 2013 were obtained from several sources. Fold differences were used to compare total investment, award number, mean and median award value between male and female PIs. Mann-Whitney U tests were performed to determine statistically significant associations between PI gender and median grant value. RESULTS: Of the studies included in our analysis, 2890 (69%) grants with a total value of £1.82 billion (78%) were awarded to male PIs compared with 1296 (31%) grants with a total value of £512 million (22%) awarded to female PIs. Male PIs received 1.3 times the median award value of their female counterparts (P<0.001). These apparent absolute and relative differences largely persisted regardless of subanalyses. CONCLUSIONS: We demonstrate substantial differences in cancer research investment awarded by gender. Female PIs clearly and consistently receive less funding than their male counterparts in terms of total investment, the number of funded awards, mean funding awarded and median funding awarded.

Progressive right ventricular enlargement due to pulmonary regurgitation: Clinical characteristics of a "low-risk" group.

BACKGROUND: The optimal interval between serial cardiac magnetic resonance imaging (CMRI) scans for monitoring right ventricular (RV) enlargement in the setting of severe pulmonic valve regurgitation (PR) is unknown. The purposes of this study were to (1) determine the annual change in RV volume on serial CMRI scans and (2) identify the risk factors for rapid progression of RV enlargement. METHODS: A retrospective study of adults with postintervention native valve PR and ≥2 CMRI scans at Mayo Clinic Rochester from 2000 to 2015 was conducted. Rapid progression of RV enlargement was defined as first upper quartile of annual increase in RV end-diastolic volume index (RVEDVi) for the cohort. RESULTS: Of the 63 patients (age, 36 ±â€¯9 years) in the study, 43 (68%) had tetralogy of Fallot, whereas 20 (32%) had valvular pulmonic stenosis. Right ventricular outflow tract interventions that resulted in PR were balloon pulmonary valvuloplasty (n = 4; 7%), transannular patch repair (n = 30; 58%), and nontransannular patch repair (n = 18; 35%). Interval between baseline and second CMRI was 2 (1-4) years. In comparison to baseline CMRI, RVEDVi increased from 130 (109-141) to 135 (126-155) mL/m2 and median annual change in RVEDVi was 3.1 (1.7-5.9) mL/m2. Univariate risk factors for rapid progression of RV enlargement (annual increase in RVEDVi >6 mL/m2) were ≥moderate tricuspid regurgitation and RVEDVi >130 mL/m2. Among the 24 patients without these risk factors (low-risk subgroup), RVEDVi increased by only 3 (0-7) mL/m2 over 7 (5-9) years. CONCLUSIONS: Patients with PR without RVEDVi >130 mL/m2 and/or ≥moderate tricuspid regurgitation represent a low-risk subgroup that may be appropriate for clinical and echo follow-up but may potentially require infrequent CMRI follow-up.