Heart Rate at Rest and Incident Atrial Fibrillation in Patients With Diastolic Dysfunction.

Diastolic dysfunction (DD) is associated with incident atrial fibrillation (AF). The influence of heart rate at rest (RHR) on incident AF in patients with DD has not been investigated. The goal of this study is to assess the influence of RHR on incident AF in patients with DD. Patients from a large health system with no previous history of AF, a left ventricular ejection fraction ≥50%, and documented DD on echocardiography were divided into quartiles (<66, 66 to 76, 77 to 91, >91 beats per minute) based on RHR. Incident AF was estimated using AF hospitalization during follow-up. Hazard ratios (HR) for AF hospitalization and all-cause death were calculated with a Cox proportional hazards model. A total of 19,046 patients were analyzed. Over a median follow-up of 42.2 months, 742 (3.9%) patients were hospitalized for AF. Both slower and faster RHR were associated with increased risk of AF hospitalization (HR 1.40, confidence interval [CI] 1.14 to 1.71, p = 0.001, HR 1.23, CI 0.99 to 1.53, p = 0.06 and HR 1.72, CI 1.38 to 2.14, p <0.001, for quartiles 1, 2, and 4, respectively), suggesting a J-shaped relation. Progressive increase in all-cause death was noted with faster RHR (HR1.19 per quartile increase, CI 1.16 to 1.22, p <0.001). These results persisted after adjustment for age, cardiovascular co-morbidities, grade of DD, and ß-blocker use. In conclusion, this large, real-world analysis indicates increased risk of incident AF with slower and faster RHR in patients with DD. Randomized trials are needed to evaluate the potential of RHR modification to mitigate the risk of incident AF.

Patient Outcomes by Ventricular Systolic and Diastolic Function.

BACKGROUND: Left ventricular dysfunction is characterized by systolic and diastolic parameters, leading to heart failure (HF) with reduced or preserved ejection fraction (EF), respectively. The goal of this study is to examine the impact of left ventricular systolic and diastolic dysfunction (DD) on patient outcomes. METHODS AND RESULTS: Two cohorts were used in this analysis: Cohort A included 136 455 patients with EF ≥50%, stratified by the presence and grade of DD. Cohort B included 16 850 patients with EF <50%, stratified by EF quartiles. Patients were followed to the end points of all-cause death and cardiovascular, HF, or cardiac arrest hospitalizations. Over a median follow-up of 3.42 years, 23 946 (16%) patients died and 31 113 (20%), 13 305 (9%), and 1269 (1%) were hospitalized for cardiovascular, HF, or cardiac arrest causes, respectively. With adjustment for comorbidities, the risk of all-cause mortality and of cardiovascular and HF hospitalizations increased steadily with increasing grade of DD in patients with normal EF, and even more so in patients with worsening EF. The risk of hospitalization for cardiac arrest in patients with grade III DD, however, was comparable to that of patients with EF <25% (hazard ratio, 1.00 [95% CI, 0.98-1.01]) and worse than that of patients in better EF quartiles. CONCLUSIONS: Although systolic dysfunction is associated with a greater risk of overall death and HF hospitalizations than DD, the risk of cardiac arrest in patients with grade II and III DD is comparable to that of patients with moderate and severe systolic dysfunction, respectively. Future studies are needed to examine treatment strategies than can improve these outcomes.

Association of pre-left ventricular assist device defibrillator shocks for ventricular arrhythmia with clinical outcomes after left ventricular assist device implantation.

Background: Implantable cardioverter-defibrillation (ICD) shocks after left ventricular assist device therapy (LVAD) are associated with adverse clinical outcomes. Little is known about the association of pre-LVAD ICD shocks on post-LVAD clinical outcomes and whether LVAD therapy affects the prevalence of ICD shocks. Objectives: The purpose of this study was to determine whether pre-LVAD ICD shocks are associated with adverse clinical outcomes post-LVAD and to compare the prevalence of ICD shocks before and after LVAD therapy. Methods: Patients 18 years or older with continuous-flow LVADs and ICDs were retrospectively identified within the University of Pittsburgh Medical Center system from 2006-2020. We analyzed the association between appropriate ICD shocks within 1 year pre-LVAD with a primary composite outcome of death, stroke, and pump thrombosis and secondary outcomes of post-LVAD ICD shocks and ICD shock hospitalizations. Results: Among 309 individuals, average age was 57 ± 12 years, 87% were male, 80% had ischemic cardiomyopathy, and 42% were bridge to transplantation. Seventy-one patients (23%) experienced pre-LVAD shocks, and 69 (22%) experienced post-LVAD shocks. The overall prevalence of shocks pre-LVAD and post-LVAD were not different. Pre-LVAD ICD shocks were not associated with the composite outcome. Pre-LVAD ICD shocks were found to predict post-LVAD shocks (hazard ratio [HR] 5.7; 95% confidence interval [CI] 3.42-9.48; P <.0001) and hospitalizations related to ICD shocks from ventricular arrhythmia (HR 10.34; 95% CI 4.1-25.7; P <.0001). Conclusion: Pre-LVAD ICD shocks predicted post-LVAD ICD shocks and hospitalizations but were not associated with the composite outcome of death, pump thrombosis, or stroke at 1 year. The prevalence of appropriate ICD shocks was similar before and after LVAD implantation in the entire cohort.

Commotio Cordis Returns When We Least Expected It: Cardiac Arrest in A Professional Football Player.

For the first time in 52 years, an American professional football player (Damar Hamlin) collapsed in cardiac arrest during a game, viewed in real-time on national television. The cause of this profound event was commotio cordis, that is, blunt non-penetrating chest blow-initiated ventricular fibrillation triggered by physical contact not considered unusual for football. The athlete survived because of timely cardiopulmonary resuscitation and defibrillation provided by first responders organized by the National Football League. Commotio cordis, albeit rare, was most prominently identified initially in competitive and also recreational sports participants. More recently it became apparent that similar events could occur in almost any circumstance involving a chest blow, such as during everyday activities around the home and with innocent play. The determinant of a commotio cordis event is a blow over the heart in a narrow vulnerable electrical window during dispersion of repolarization. Survival from these events has increased substantially to >60% due to enhanced recognition and prompt resuscitation/defibrillation. In conclusion, in this commentary, we take a timely opportunity to describe in detail the relevant demographics, mechanism/pathophysiology, and clinical course of commotio cordis.

Development of the Implantable Cardioverter-Defibrillator: JACC Historical Breakthroughs in Perspective.

Implantable cardioverter-defibrillators (ICDs) represent transformational technology, arguably the most significant advance in cardiovascular medicine in 50 years. The vision and determination of pioneers Mirowski and Mower was fundamental to this monumental achievement, working with limited resources and confronted by skepticism/criticism from medical establishment. The inventors were followed >35 years in which a multitude of innovative clinical scientists and engineers introduced technological advances leading to the sophisticated devices in practice today. A pivotal patient experiment with automated termination of ventricular fibrillation (1980) led to U.S. Food and Drug Administration approval. Transvenous lead systems converted ICDs from thoracotomy-based secondary prevention to primary prevention of sudden death devices in countless patients worldwide. ICD acceptance was solidified by prospective randomized controlled trials showing reduced mortality superior to antiarrhythmic drugs. ICDs eventually expanded from coronary disease to inherited arrhythmia conditions (eg, hypertrophic cardiomyopathy). The ICD breakthrough story demonstrates how significant progress is possible in medicine against all odds, given fearless imagination to pursue novel ideas that conflict with accepted wisdom.

Vigorous Exercise in Patients With Hypertrophic Cardiomyopathy.

Importance: Whether vigorous intensity exercise is associated with an increase in risk of ventricular arrhythmias in individuals with hypertrophic cardiomyopathy (HCM) is unknown. Objective: To determine whether engagement in vigorous exercise is associated with increased risk for ventricular arrhythmias and/or mortality in individuals with HCM. The a priori hypothesis was that participants engaging in vigorous activity were not more likely to have an arrhythmic event or die than those who reported nonvigorous activity. Design, Setting, and Participants: This was an investigator-initiated, prospective cohort study. Participants were enrolled from May 18, 2015, to April 25, 2019, with completion in February 28, 2022. Participants were categorized according to self-reported levels of physical activity: sedentary, moderate, or vigorous-intensity exercise. This was a multicenter, observational registry with recruitment at 42 high-volume HCM centers in the US and internationally; patients could also self-enroll through the central site. Individuals aged 8 to 60 years diagnosed with HCM or genotype positive without left ventricular hypertrophy (phenotype negative) without conditions precluding exercise were enrolled. Exposures: Amount and intensity of physical activity. Main Outcomes and Measures: The primary prespecified composite end point included death, resuscitated sudden cardiac arrest, arrhythmic syncope, and appropriate shock from an implantable cardioverter defibrillator. All outcome events were adjudicated by an events committee blinded to the patient's exercise category. Results: Among the 1660 total participants (mean [SD] age, 39 [15] years; 996 male [60%]), 252 (15%) were classified as sedentary, and 709 (43%) participated in moderate exercise. Among the 699 individuals (42%) who participated in vigorous-intensity exercise, 259 (37%) participated competitively. A total of 77 individuals (4.6%) reached the composite end point. These individuals included 44 (4.6%) of those classified as nonvigorous and 33 (4.7%) of those classified as vigorous, with corresponding rates of 15.3 and 15.9 per 1000 person-years, respectively. In multivariate Cox regression analysis of the primary composite end point, individuals engaging in vigorous exercise did not experience a higher rate of events compared with the nonvigorous group with an adjusted hazard ratio of 1.01. The upper 95% 1-sided confidence level was 1.48, which was below the prespecified boundary of 1.5 for noninferiority. Conclusions and Relevance: Results of this cohort study suggest that among individuals with HCM or those who are genotype positive/phenotype negative and are treated in experienced centers, those exercising vigorously did not experience a higher rate of death or life-threatening arrhythmias than those exercising moderately or those who were sedentary. These data may inform discussion between the patient and their expert clinician around exercise participation.

Guideline-Directed Medical Therapy and the Risk of Death in Primary Prevention Defibrillator Recipients.

BACKGROUND: Contemporary guideline-directed medical therapy (GDMT) confers a significant mortality benefit for patients with heart failure with reduced ejection fraction (HFrEF), as compared to GDMT prevalent at the time of landmark primary prevention implantable cardioverter-defibrillator (ICD) trials. The impact of modern era GDMT on survival in this population is unknown. OBJECTIVES: This study sought to investigate the impact of number of GDMT medications prescribed for HFrEF on all-cause mortality in recipients of primary prevention ICD. METHODS: A cohort of 4,972 recipients with primary prevention ICD (n = 3,210) or cardiac resynchronization therapy-defibrillator (CRT-D) (n = 1,762) was studied. The association of number of GDMT medications prescribed at the time of device implantation and all-cause mortality at 2 years post implantation was examined. RESULTS: In our primary prevention cohort, 5%, 20%, 52%, and 23% of patients were prescribed 0, 1, 2, or 3-4 GDMT medications, respectively. After risk adjustment for age, sex, ejection fraction, body mass index, the Elixhauser comorbidity score, the type of cardiomyopathy, and the year of device implantation, each additional GDMT conferred a reduction in the risk of death of 36% in recipients of ICD (HR: 0.64; P < 0.001) and 30% in recipients of CRT-D (HR: 0.70; P < 0.001). CONCLUSIONS: A higher number of prescribed GDMT medications is associated with an incremental 1-year survival in recipients of primary prevention ICD with or without CRT. Initiation of maximum number of tolerated GDMT medications should therefore be the goal for all patients with HFrEF. In the setting of robust GDMT, the risk versus benefit of a primary prevention ICD warrants re-examination in future studies.

Impact of an Automated Best Practice Alert on Sex and Race Disparities in Implantable Cardioverter-Defibrillator Therapy.

Background Implantable cardioverter-defibrillators (ICDs) are indicated in patients with severe left ventricular dysfunction, but many eligible patients do not receive them, especially women and Black patients. Our group had previously demonstrated that a best practice alert (BPA) improves overall rates of electrophysiology referrals and ICD implantations. This study examined the impact of a BPA by sex and race. Methods and Results This is a cluster randomized trial of cardiology (n=106) and primary care (n=89) providers who were randomized to receive (BPA, n=93) or not receive (No BPA, n=102) the alert and managed 1856 patients meeting primary prevention criteria for ICD implantation (965 BPA and 891 No BPA). After a median follow up of 34 months, 630 (34%) patients were referred to electrophysiology, and 522 (28%) patients received an ICD. Compared with the No BPA arm, patients in the BPA arm saw a modest differential increase in the rate of electrophysiology referrals at 18 months in men (+4%) compared with women (+7%) but a profound increase in Black patients (+16%) compared with White patients (+2%), thus closing the sex and race gaps. Similar trends were noted for rates of ICD implantation. Conclusions Use of a BPA improves rates of electrophysiology referrals and ICD implantations in all comers with severe cardiomyopathy and no prior ventricular arrhythmias but has a more pronounced impact in women and Black patients. The use of a BPA at the point of care is an effective tool in the fight against sex and race inequities in health care.

Predictors of Hospital Admissions for Ventricular Arrhythmia or Cardiac Arrest in Patients With Cardiomyopathy.

Although ventricular dysfunction is associated with the occurrence of ventricular arrhythmia (VA), most patients with cardiomyopathy do not experience VA. We therefore investigated other predictors of VA in a large contemporary cohort of patients with cardiomyopathy. All patients at a large academic medical system with left ventricular ejection fraction (LVEF) ≤50% were enrolled at the time of first documented low LVEF. Predictors of hospital admission for VA were examined using multivariable Cox models. The incidence of implantable defibrillator (ICD) placement was also examined. A total of 18,003 patients were enrolled. Over a median follow-up of 3.35 years, 389 patients (2.2%) were admitted for VA (304 of 12,037 [2.5%] among patients with LVEF ≤35% vs 85 of 5,966 [1.4%] among those with LVEF 36% to 50%). Predictors of VA hospitalization included lower LVEF (hazard ratio (HR) = 1.43 per 10% decrease, p <0.001), the presence of an ICD at baseline (HR = 1.63, p = 0.010), higher blood glucose (HR = 1.02 per 10 mg/100 ml increase, p = 0.050), the presence of end-stage renal disease (HR = 3.59, p <0.001), and the presence of liver cirrhosis (HR = 1.93, p = 0.013). During follow-up, 626 patients were implanted with a new ICD. In addition to being admitted with VA, a lower LVEF and a history of coronary artery disease or heart failure were the main predictors of ICD therapy in this population. In conclusion, in addition to more severe cardiomyopathy and the presence of an implanted ICD, metabolic derangements on initial contact are independent predictors of hospital admissions for VA in patients with cardiomyopathy. Noncardiac co-morbidities play an important role in stratifying patients with cardiomyopathy for their risk of VA or cardiac arrest.

Ventricular pacing and myocardial function in patient with congenital heart block.

INTRODUCTION: Pacing-induced cardiomyopathy (PICM) is a potential complication of chronic right ventricular (RV) pacing, but its characterization in adult patients is often complicated by pre-existing cardiomyopathy. This study investigated the incidence of PICM in patients with congenital heart block (cHB) who have conduction disease from birth without confounding pre-existing cardiac conditions. METHODS AND RESULTS: This retrospective cohort analysis included 42 patients with cHB and baseline left ventricular ejection fraction (LVEF) ≥50%. Kaplan-Meier analysis was used to assess freedom from cardiomyopathy (defined as LVEF <50%) between paced and nonpaced patients. Patients were 26 ± 3 years old at first presentation, 64% were women and baseline LVEF was 60.0 ± 0.2%. Median follow-up from birth was 35 (interquartile range [IQR]: 20-42) years with a median of 6.7 years (IQR: 3.6-9.2) at our institution. Thirty-two patients received pacing at mean age 21 ± 3 years. Patients receiving a pacemaker (PM) were significantly more likely to develop a cardiomyopathy (p = .021) and no patient developed a cardiomyopathy in the absence of a PM. Four patients who developed a new cardiomyopathy were upgraded to biventricular pacing, leading to stabilization or improvement of LVEF. CONCLUSION: In a relatively young and healthy cHB cohort, RV pacing is associated with a higher risk of developing a cardiomyopathy. These data confirm the deleterious effects of RV pacing on myocardial function in patients without pre-existing structural cardiac disease and has clinical implications to the management of patients with cHB.

Energy Drink-Associated Electrophysiological and Ischemic Abnormalities: A Narrative Review.

An increasing number of cardiovascular adverse effects, emergency room visits, and deaths have been linked to energy drinks. In this review, we summarized available published literature assessing electrophysiological and ischemic adverse effects associated with energy drink consumption. Overall, 32 case reports and 19 clinical trials are included in this review. Ventricular arrhythmia, supraventricular arrhythmia, and myocardial ischemia were amongst the most commonly reported in case reports with 3 having a fatal outcome. Although serious ischemic changes, arrhythmias, or death were not observed in clinical trials, significant electrophysiological changes, such as PR/PQ interval shortening/prolongation, QT/QTc shortening/prolongation, and ST-T changes, were noted. QT/QTc interval prolongation appears to be the most significant finding in clinical trials, and there appears to be a dose-response relationship between energy drink consumption and QTc prolongation. The exact mechanisms and the particular combination of ingredients behind energy drink-induced cardiac abnormalities require further evaluation. Until more information is available, energy drink use should be considered as part of the differential diagnosis in appropriate patients presenting with electrocardiographic changes. Further, certain patient populations should exercise caution and limit their energy drink consumption.