Impact of comorbidities on atrial fibrillation and sudden cardiac death in hypertrophic cardiomyopathy.

BACKGROUND: The impact of comorbid disease states on the development of atrial and ventricular arrhythmias in patients with hypertrophic cardiomyopathy (HCM) remains unresolved. OBJECTIVE: Evaluate the association of comorbidities linked to arrhythmias in other cardiovascular diseases (e.g., obesity, systemic hypertension, diabetes, obstructive sleep apnea, renal disorders, tobacco, and alcohol use) to atrial fibrillation (AF) and sudden cardiac death (SCD) events in a large cohort of HCM patients. METHODS: A total  of 2269 patients, 54 ± 15 years of age, 1392 males, were evaluated at the Tufts HCM Institute between 2004 and 2018 and followed for an average of 4 ± 3 years for new-onset clinical AF and SCD events (appropriate defibrillation for ventricular tachyarrhythmias, resuscitated cardiac arrest, or SCD). RESULTS: One or more comorbidity was present in 75% of HCM patients, including 50% with ≥2 comorbidities, most commonly obesity (body mass index [BMI] ≥ 30 kg/m2 ) in 43%. New-onset atrial fibrillation developed in 11% of our cohort (2.6%/year). On univariate analysis, obesity was associated with a 1.7-fold increased risk for AF (p = .03) with 12% of obese patients developing AF (3.3%/year) as compared to 7% of patients with BMI < 25 kg/m2 (1.6%/year; p = .006). On multivariate analysis, age and LA transverse dimension emerged as the only variables predictive of AF. Comorbidities, including obesity, were not independently associated with AF development (p > .10 for each). SCD events occurred in 3.3% of patients (0.8%/year) and neither obesity nor other comorbidities were associated with increased risk for SCD (p > .10 for each). CONCLUSIONS: In adult HCM patients comorbidities do not appear to impact AF or SCD risk. Therefore, for most patients with HCM, adverse disease related events of AF and SCD appear to be primarily driven by underlying left ventricular and atrial myopathy as opposed to comorbidities.

Bayés syndrome secondary to atrial lipoma.

This case describes a 74-year-old male who presented with rapid atrial flutter in association with large atrial lipoma along the interatrial septum. Conversion to sinus rhythm revealed the electrocardiographic criteria for advanced interatrial block. Interatrial block results from disruption of conduction through Bachmann's bundle, most commonly due to progressive atrial fibrosis. Bayés syndrome is recognized as the association of atrial arrhythmias with underlying interatrial block. This case supports the concept that localized disruption of atrial conduction via Bachmann's bundle from an atrial lipoma can produce the electrophysiologic substrate for atrial arrhythmias and the Bayés syndrome.

The Convergent Procedure: A Unique Multidisciplinary Hybrid Treatment of Atrial Fibrillation.

The convergent procedure is a hybrid ablation treatment for atrial fibrillation. It is increasingly considered as a management option for patients with persistent and long-standing atrial fibrillation. It consists of surgical ablation of the posterior left atrium through a minimally invasive closed-chest approach followed by endocardial catheter ablation. It is increasingly performed with concurrent epicardial occlusion of the left atrial appendage with a video-assisted thoracoscopic technique to physically and electrically isolate the left atrial appendage. This article provides an overview of a multidisciplinary approach to the convergent procedure, with concurrent thoracoscopic closure of the left atrial appendage, with an emphasis on perioperative management at a single institution. It provides a literature review of procedural outcomes, current data limitations, and future considerations.

Watching for Disease: the Changing Paradigm of Disease Screening in the Age of Consumer Health Devices.

There has been a recent proliferation of consumer health devices (CHDs) that enable user-initiated screening for a variety of diseases. These devices represent a paradigm shift in the deployment of disease screening, a process that has historically been led by clinicians following the guidance of professional bodies. The detection of AF via CHDs is a contemporary example of this phenomenon and highlights several important implications of the shift of disease screening from clinicians to CHD users. These include responsibility for patient data and outcomes, healthcare costs and access, and an evolution of the patient-provider relationship. However, as CHD technologies mature and become more affordable, they have the potential to detect actionable subclinical disease and improve health. Rather than allow CHDs to enter the marketplace organically with the potential for unintended negative consequences, it is critical that clinical, research, and industry communities proactively collaborate and establish best practices for their use.

Use of ultrasound enhancing agents in transesophageal echocardiography to improve interpretive confidence of left atrial appendage thrombus.

BACKGROUND: The value of ultrasound enhancing agents (UEA) in patients undergoing transesophageal echocardiography (TEE) for the exclusion of left atrial appendage (LAA) thrombi prior to direct current cardioversion (DCCV) is evolving. METHODS: We retrospectively identified 88 consecutive TEEs, where a commercial UEA was used during LAA interrogation. De-identified non-enhanced (pre-UEA) and enhanced cine loop images (post-UEA) from the same subjects were randomly reviewed by four expert readers in a blinded fashion. RESULTS: In 33% of the cases, UEA use was associated with a statistically insignificant improvement in physician confidence (scale, 0-3) in determining the presence or absence of a LAA thrombus (P = 0.071). In instances where non-enhanced images yielded an uncertain interpretation or when the left atrium contained spontaneous echo contrast (SEC), UEA use was associated with an improvement in interpretive confidence in 49% (P < 0.001) and 41% of the cases (P = 0.001), respectively. Overall, the absolute rate of hypothetical decision to proceed with DCCV rose by 9% with the application of UEA (P = 0.004). In instances where non-enhanced images were interpreted with limited confidence or when SEC was present, there were absolute increases of 16% (P < 0.001) and 21% (P < 0.001) in hypothetical procession to DCCV, respectively. In cases of a combination of limited interpretive confidence and SEC, UEA use was associated with a 29% absolute increase in the rate of procession to DCCV (P < 0.001). CONCLUSIONS: In patients undergoing TEE interrogation of the LAA, the use of UEA is associated with an increase in the level of interpretive confidence and higher rates of theoretical procession to DCCV.

Reassessing Risk Factors for High Defibrillation Threshold: The EF-SAGA Risk Score and Implications for Device Testing.

OBJECTIVES: To reevaluate risk factors for high defibrillation threshold (DFT) and propose a risk assessment tool. BACKGROUND: Controversy exists over routine DFT testing during implantable cardioverter defibrillator (ICD) placement. METHODS: We retrospectively analyzed 1,642 consecutive patients who received an ICD and underwent DFT testing. RESULTS: The incidence of high DFT requiring addition of a subcutaneous array was 2.3%. Five significant independent variables predictive of high DFT were identified, including younger age, male gender (hazard ratio 1.99), left ventricular (LV) dysfunction, secondary prevention (hazard ratio 2.33), and amiodarone use (hazard ratio 2.39). Each 10-year increase in age was indicative of a 0.35-times lower chance of high DFT. Each 10% increase of LV ejection fraction (EF) was indicative of a 0.52-times lower chance of high DFT. These five variables form the EF-SAGA risk score (LVEF < 20%, Secondary prevention ICD indication, Age < 60 years, male Gender, Amiodarone use). Cumulative risk of high DFT increased incrementally; patients with four or more variables had an 8.9% likelihood of high DFT. Importantly, primary prevention patients with LVEF > 20% had a negative predictive value for high DFT of 99.3%. CONCLUSION: We identified five independent predictors of high DFT. We propose the EF-SAGA risk score to help decision making. Primary prevention patients with an LVEF > 20% had an exceedingly low incidence of high DFT suggesting that testing could be avoided in these patients. Careful assessment of the risk-benefit ratio of testing is important in high-risk patients.

Identification of high-risk imaging features in hypertrophic cardiomyopathy using electrocardiography: A deep-learning approach.

BACKGROUND: Patients with hypertrophic cardiomyopathy (HCM) are at risk of sudden death, and individuals with ≥1 major risk markers are considered for primary prevention implantable cardioverter-defibrillators. Guidelines recommend cardiac magnetic resonance (CMR) imaging to identify high-risk imaging features. However, CMR imaging is resource intensive and is not widely accessible worldwide. OBJECTIVE: The purpose of this study was to develop electrocardiogram (ECG) deep-learning (DL) models for the identification of patients with HCM and high-risk imaging features. METHODS: Patients with HCM evaluated at Tufts Medical Center (N = 1930; Boston, MA) were used to develop ECG-DL models for the prediction of high-risk imaging features: systolic dysfunction, massive hypertrophy (≥30 mm), apical aneurysm, and extensive late gadolinium enhancement. ECG-DL models were externally validated in a cohort of patients with HCM from the Amrita Hospital HCM Center (N = 233; Kochi, India). RESULTS: ECG-DL models reliably identified high-risk features (systolic dysfunction, massive hypertrophy, apical aneurysm, and extensive late gadolinium enhancement) during holdout testing (c-statistic 0.72, 0.83, 0.93, and 0.76) and external validation (c-statistic 0.71, 0.76, 0.91, and 0.68). A hypothetical screening strategy using echocardiography combined with ECG-DL-guided selective CMR use demonstrated a sensitivity of 97% for identifying patients with high-risk features while reducing the number of recommended CMRs by 61%. The negative predictive value with this screening strategy for the absence of high-risk features in patients without ECG-DL recommendation for CMR was 99.5%. CONCLUSION: In HCM, novel ECG-DL models reliably identified patients with high-risk imaging features while offering the potential to reduce CMR testing requirements in underresourced areas.

Single- Versus Dual-Chamber Implantable Cardioverter-Defibrillator for Primary Prevention of Sudden Cardiac Death in the United States.

Background Routine addition of an atrial lead during an implantable cardioverter-defibrillator (ICD) implantation for primary prevention of sudden cardiac death, in patients without pacing indications, was not shown beneficial in contemporary studies. We aimed to investigate the use and safety of single- versus dual-chamber ICD implantations in these patients. Methods and Results Using the National Inpatient Sample database, we identified patients with no pacing indications who underwent primary-prevention ICD implantation in the United States between 2015 and 2019. Sociodemographic and clinical characteristics, as well as in-hospital complications, were analyzed. Multivariable logistic regression was used to identify predictors of in-hospital complications. An estimated total of 15 940 patients, underwent ICD implantation for primary prevention of sudden cardiac death during the study period, 8860 (55.6%) received a dual-chamber ICD. The mean age was 64 years, and 66% were men. In-hospital complication rates in the dual-chamber ICD and single-chamber ICD group were 12.8% and 10.7%, respectively (P<0.001), driven by increased rates of pneumothorax/hemothorax (4.6% versus 3.4%; P<0.001) and lead dislodgement (3.6% versus 2.3%; P<0.001) in the dual-chamber ICD group. Multivariable analyses confirmed atrial lead addition as an independent predictor for "any complications" (odds ratio [OR], 1.1 [95% CI, 1.0-1.2]), for pneumo/hemothorax (odds ratio, 1.1 [95% CI, 1.0-1.4]), and for lead dislodgement (odds ratio, 1.3 [95% CI, 1.1-1.6]). Conclusions Despite lack of evidence for clinical benefit, dual-chamber ICDs are implanted for primary prevention of sudden cardiac death in a majority of patients who do not have pacing indication. This practice is associated with increased risk of periprocedural complications. Avoidance of routine implantation of atrial leads will likely improve safety outcomes.

Intercostal muscle twitching from right ventricular apical pacing.

A patient with a dilated cardiomyopathy underwent successful implantation of a cardiac resynchronization therapy defibrillator. The device system included an active fixation lead placed at the right ventricular (RV) apex. Pacing from the RV apex unexpectedly led to left-sided intercostal muscle stimulation and twitching. This intercostal muscle twitching resolved completely with movement of the lead to the RV outflow tract.

Cats Have Nine Lives but This Hypertrophic Cardiomyopathy Patient Has Had Ten (So Far).

In this report, we describe the unusual but highly informative clinical course of a high-risk hypertrophic cardiomyopathy patient who has to date experienced 10 appropriate primary prevention implantable cardioverter-defibrillator therapies terminating ventricular fibrillation over a 19-year period. Most patients in the Tufts HCM cohort with primary prevention experienced either 1 such therapy (66%) or 1 to 3 interventions (91%) over time. These observations underscore the opportunity for sudden death prevention in hypertrophic cardiomyopathy attributable to efficacy of the implanted defibrillator and the reliability of the American Heart Association/American College of Cardiology individual risk marker strategy.

Marked variability in susceptibility to ventricular fibrillation in an experimental commotio cordis model.

BACKGROUND: Precordial blows in sports and daily activities can trigger ventricular fibrillation (VF) (commotio cordis). Whereas chest wall blows are common, commotio cordis is rare. Although factors such as timing, location, orientation, and energy of impact are critically important, we also hypothesize that there is individual susceptibility to commotio cordis. Using our model of commotio cordis, we evaluated individual animal susceptibility to VF induction and assessed animal characteristics that might be involved. METHODS AND RESULTS: This retrospective analysis included 139 juvenile swine (weight, 8 to 54 kg) that were anesthetized and placed prone in a sling to receive chest wall strikes with a ball propelled at 30 to 40 mph. Each animal received a minimum of 4 impacts directly over the cardiac silhouette, all timed to a narrow vulnerable window during cardiac repolarization. Of 1274 total impacts, 360 impacts (28%) resulted in VF. There was wide variability in individual animal susceptibility to VF. In 38 animals, none of the impacts resulted in VF (range, 4 to 18 impacts per animal). The majority of animals (91; 65%) were induced into VF with <30% of the strikes. In fact, only 19 animals (14%) had >50% occurrence of VF with chest wall impacts, and only 7 (5%) had >80% occurrence of chest impacts that induced VF. In the animal-based analysis, individual correlates of VF included animal weight, mean impact velocity, mean left ventricular pressure generated by the blow, mean QRS duration, mean QTc, and QTc variability. In multivariable analysis, mean left ventricular pressure generated by the blow, mean QRS duration, and QTc variability remained significant correlates of risk, and number of impacts gained statistical significance such that animals with more impacts were less susceptible to VF. CONCLUSIONS: Swine display a wide range of individual vulnerability to VF triggered by chest wall impact, with a distinct minority being uniquely susceptible. Mild abnormalities in cardiac depolarization and repolarization might underlie this susceptibility. Such individual susceptibility may also be present in humans and contribute to the rarity of commotio cordis.

Parasympathetic response in chick myocytes and mouse heart is controlled by SREBP.

Parasympathetic stimulation of the heart, which provides protection from arrhythmias and sudden death, involves activation of the G protein-coupled inward rectifying K+ channel GIRK1/4 and results in an acetylcholine-sensitive K+ current, I KACh. We describe a unique relationship between lipid homeostasis, the lipid-sensitive transcription factor SREBP-1, regulation of the cardiac parasympathetic response, and the development of ventricular arrhythmia. In embryonic chick atrial myocytes, lipid lowering by culture in lipoprotein-depleted serum increased SREBP-1 levels, GIRK1 expression, and I KACh activation. Regulation of the GIRK1 promoter by SREBP-1 and lipid lowering was dependent on interaction with 2 tandem sterol response elements and an upstream E-box motif. Expression of dominant negative SREBP-1 (DN-SREBP-1) reversed the effect of lipid lowering on I KACh and GIRK1. In SREBP-1 knockout mice, both the response of the heart to parasympathetic stimulation and the expression of GIRK1 were reduced compared with WT. I KACh, attenuated in atrial myocytes from SREBP-1 knockout mice, was stimulated by SREBP-1 expression. Following myocardial infarction, SREBP-1 knockout mice were twice as likely as WT mice to develop ventricular tachycardia in response to programmed ventricular stimulation. These results demonstrate a relationship between lipid metabolism and parasympathetic response that may play a role in arrhythmogenesis.

Role of SREBP-1 in the development of parasympathetic dysfunction in the hearts of type 1 diabetic Akita mice.

RATIONALE: Diabetic autonomic neuropathy (DAN), a major complication of diabetes mellitus, is characterized, in part, by impaired cardiac parasympathetic responsiveness. Parasympathetic stimulation of the heart involves activation of an acetylcholine-gated K+ current, I(KAch), via a (GIRK1)2/(GIRK4)2 K+ channel. Sterol regulatory element binding protein-1 (SREBP-1) is a lipid-sensitive transcription factor. OBJECTIVE: We describe a unique SREBP-1-dependent mechanism for insulin regulation of cardiac parasympathetic response in a mouse model for DAN. METHODS AND RESULTS: Using implantable EKG transmitters, we demonstrated that compared with wild-type, Ins2(Akita) type I diabetic mice demonstrated a decrease in the negative chronotropic response to carbamylcholine characterized by a 2.4-fold decrease in the duration of bradycardia, a 52+/-8% decrease in atrial expression of GIRK1 (P<0.01), and a 31.3+/-2.1% decrease in SREBP-1 (P<0.05). Whole-cell patch-clamp studies of atrial myocytes from Akita mice exhibited a markedly decreased carbamylcholine stimulation of I(KAch) with a peak value of -181+/-31 pA/pF compared with -451+/-62 pA/pF (P<0.01) in cells from wild-type mice. Western blot analysis of extracts of Akita mice demonstrated that insulin treatment increased the expression of GIRK1, SREBP-1, and I(KAch) activity in atrial myocytes from these mice to levels in wild-type mice. Insulin treatment of cultured atrial myocytes stimulated GIRK1 expression 2.68+/-0.12-fold (P<0.01), which was reversed by overexpression of dominant negative SREBP-1. Finally, adenoviral expression of SREBP-1 in Akita atrial myocytes reversed the impaired I(KAch) to levels in cells from wild-type mice. CONCLUSIONS: These results support a unique molecular mechanism for insulin regulation of GIRK1 expression and parasympathetic response via SREBP-1, which might play a role in the pathogenesis of DAN in response to insulin deficiency in the diabetic heart.

Exercise and Athletic Activity in Atrial Fibrillation.

Moderate-intensity exercise improves cardiovascular outcomes. However, mounting clinical evidence demonstrates that long-term, high-intensity endurance training predisposes male and veteran athletes to an increased risk of atrial fibrillation (AF), a risk that is not observed across both genders. Although increased mortality associated with AF in the general population is not shared by athletes, clinically significant morbidities exist (eg, reduced exercise capacity, athletic performance, and quality of life). Additional research is needed to fill current gaps in knowledge pertaining to the natural history, pathophysiologic mechanisms, and management strategies of AF in the athlete.

Quadripolar versus bipolar leads in cardiac resynchronization therapy: An analysis of the National Cardiovascular Data Registry.

BACKGROUND: The introduction of quadripolar (QP) cardiac resynchronization therapy (CRT) leads aimed to improve procedural and clinical outcomes. OBJECTIVE: The National Cardiovascular Data Registry was analyzed to characterize the use as well as the procedural and clinical outcomes of QP leads in comparison with unipolar and bipolar (BP) leads. METHODS: We evaluated data on 175,684 procedures reported between September 1, 2010, and December 31, 2015. Clinical outcomes were analyzed using Centers for Medicare & Medicaid Services claims data. RESULTS: Among all CRT device implants, there was a drop in reported lead placement failure from 6.04% to 5.21% (P < .0001 for trend) and a drop in the reported diaphragmatic stimulation rates from 0.07% to 0.01% (P < .007 for trend) between the last quarters of 2010 and 2015. No significant difference in procedural complication rates between QP and BP leads occurred (1.34% and 1.39%, respectively; P = .50). Among patients linked to Centers for Medicare & Medicaid Services claims data, no statistically significant difference in the combined primary outcome of death, congestive heart failure admission, device malfunction, and reoperation between BP and QP leads was observed (34.15 and 34.19 events per 100 patient-years, respectively; P = .89). CONCLUSION: Since the introduction of QP leads, there was a reduction in CRT lead placement failure rates and a reduction in diaphragmatic stimulation rates. However, no statistically significant difference in long-term clinical outcomes between BP and QP leads was observed in elderly patients undergoing CRT implantation.

Long-Term Outcome in High-Risk Patients With Hypertrophic Cardiomyopathy After Primary Prevention Defibrillator Implants.

BACKGROUND: The implantable cardioverter-defibrillator (ICD) is effective for preventing sudden death in patients with hypertrophic cardiomyopathy. However, data on performance and complications of implanted ICDs over particularly long time periods to inform clinical practice is presently incomplete. METHODS: The study cohort comprises 217 consecutive hypertrophic cardiomyopathy patients with primary prevention ICDs implanted before 2008 and followed for ≥10 years (mean 12±4; range to 31). RESULTS: Patients were 38±17 years at implant and 45 (21%) experienced appropriate interventions terminating ventricular tachycardia/ventricular fibrillation. The majority of ICD discharges occurred ≥5 years after implant (29 patients; 64%), including ≥10 years in 16 patients (36%). Initial device therapy increased in frequency from 2.3% of patients at <1 year to 8.5% of patients at ≥10-years after implant (P=0.005). Inappropriate ICD shocks in 39 patients occurred most commonly <5 years after implant (54%) and decreased in frequency with increasing time from implant (from 9.7% of patients at <5 years to 3.8% at ≥10 years, P=0.02). Other major device complications including infection and lead fractures and dislodgement occurred in 27 patients (12%) but did not increase in frequency over follow-up after implant (P=0.47). There were no arrhythmic sudden death events among the 217 patients with ICD. CONCLUSIONS: In hypertrophic cardiomyopathy, after a primary prevention implant, ICD therapy often followed prolonged periods of device dormancy and increased progressively in frequency over time, including one-third of patients with initial therapy after 5 to 9 years, and an additional one-third of patients at ≥10 years. Frequency of inappropriate shocks decreased over follow-up, likely reflecting standard changes in device programming, while occurrence of device complications, such as lead fractures/infection, did not increase during follow-up.

Prediction and Prevention of Sudden Death in Young Patients (<20 years) With Hypertrophic Cardiomyopathy.

Highly reliable identification of adults with hypertrophic cardiomyopathy (HC) at risk for sudden death (SD) has been reported. A significant controversy remains, however, regarding the most reliable risk stratification methodology for children and adolescents with HC. The present study assesses the accuracy of SD prediction and prevention with prophylactic implantable cardioverter-defibrillators (ICDs) in young HC patients. The study group is comprised of 146 HC patients <20 years of age evaluated consecutively over 17 years with prospective risk stratification and ICD decision-making. We relied on ≥1 established individual risk markers considered major within each patient's clinical profile, based on an enhanced American College of Cardiology /American Heart Association (ACC/AHA) guidelines algorithm. Of the 60 largely asymptomatic patients implanted with primary prevention ICDs at age 15 ± 4 years, 9 (15%) experienced device therapy terminating potentially lethal ventricular tachyarrhythmias and restoring sinus rhythm at 19 ± 6 years (range 9 to 29), 5.1 ± 6.0 years after implant; 3 patients had multiple appropriate ICD discharges. The individual risk marker algorithm was associated with 100% sensitivity in predicting SD events (95%CI: 69, 100) and 63% specificity for identifying patients without events (95%CI: 54, 71). Of these patients with device therapy, massive left ventricular hypertrophy (absolute wall thickness ≥30 mm) was the most common predictor, present in 70% of patients either alone or in combination with other risk markers. Each of the 146 study patients have survived to date at 22 ± 5 years, including all 86 without ICD recommendations. In conclusion, an enhanced ACC/AHA risk stratification strategy, based on established individual risk markers, was highly reliable in prospectively predicting SD events in children and adolescents with HC, and preventing arrhythmia-based catastrophes in this susceptible high risk population.