Dofetilide use is not associated with increased mortality in patients with left ventricular hypertrophy and atrial fibrillation.

BACKGROUND: Left ventricular hypertrophy (LVH) is common in patients with atrial fibrillation (AF), however, many antiarrhythmic drugs (AADs) are contraindicated. US guidelines recommend avoiding pure class III antiarrhythmics such as dofetilide in patients with significant LVH due to concern for an increased risk of death, however, clinical data is lacking. We sought to determine if dofetilide use was associated with increased mortality in patients with LVH. METHODS: Patients ≥18 years of age with AF and LVH ≥ 1.4 cm were included. A group of patients treated with dofetilide and a control group of patients without a history of AAD use were propensity matched. The primary outcome was all-cause mortality at 3 years and secondary outcomes were total number of all-cause hospitalizations and hospitalizations related to AF. RESULTS: There were 359 patients in each of the groups. Baseline variables were well-matched. The primary outcome of all-cause mortality occurred in 7% of patients in the dofetilide group and 12% of patients in the control group (hazard ratio: 0.90, 95% confidence interval: 0.53-1.53). Total all-cause hospitalizations were higher in the control group but hospitalizations for AF were no different. CONCLUSIONS: In a propensity-matched cohort of 718 patients with AF and LVH, dofetilide was not associated with increased mortality at 3 years. Our study adds to prior data demonstrating the safety of dofetilide in this population despite guideline recommendations against its use. Given the limited options for AF management in LVH patients, dofetilide may be reasonable for symptomatic AF management.

A new prediction model for ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy.

AIMS: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by ventricular arrhythmias (VAs) and sudden cardiac death (SCD). We aimed to develop a model for individualized prediction of incident VA/SCD in ARVC patients. METHODS AND RESULTS: Five hundred and twenty-eight patients with a definite diagnosis and no history of sustained VAs/SCD at baseline, aged 38.2 ± 15.5 years, 44.7% male, were enrolled from five registries in North America and Europe. Over 4.83 (interquartile range 2.44-9.33) years of follow-up, 146 (27.7%) experienced sustained VA, defined as SCD, aborted SCD, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator (ICD) therapy. A prediction model estimating annual VA risk was developed using Cox regression with internal validation. Eight potential predictors were pre-specified: age, sex, cardiac syncope in the prior 6 months, non-sustained ventricular tachycardia, number of premature ventricular complexes in 24 h, number of leads with T-wave inversion, and right and left ventricular ejection fractions (LVEFs). All except LVEF were retained in the final model. The model accurately distinguished patients with and without events, with an optimism-corrected C-index of 0.77 [95% confidence interval (CI) 0.73-0.81] and minimal over-optimism [calibration slope of 0.93 (95% CI 0.92-0.95)]. By decision curve analysis, the clinical benefit of the model was superior to a current consensus-based ICD placement algorithm with a 20.3% reduction of ICD placements with the same proportion of protected patients (P < 0.001). CONCLUSION: Using the largest cohort of patients with ARVC and no prior VA, a prediction model using readily available clinical parameters was devised to estimate VA risk and guide decisions regarding primary prevention ICDs (www.arvcrisk.com).

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.

Maternal focal atrial tachycardia during pregnancy: A systematic review.

INTRODUCTION: The presentation and optimal management of maternal focal atrial tachycardia (AT) during pregnancy are unknown. The objective of this study is to conduct a comprehensive summary of the existing evidence. METHODS AND RESULTS: A systematic review of all reported cases of maternal focal AT during pregnancy was performed. The primary search queried PubMed using the MeSH terms "supraventricular tachycardia" and "pregnancy." A stepwise ancillary search included article bibliographies, citations listed by the Google internet search engine, and PubMed using the MeSH terms "atrial tachycardia" and "pregnancy." In total, 28 citations that described 32 patients were retrieved. A case from our institution was added. Detailed information was available for 30 patients. Clinical characteristics at presentation included a mean ± standard deviation of 28.3 ± 5.7 years for maternal age and 24.6 ± 7.7 weeks for gestation age. Suspected tachycardia-induced cardiomyopathy was present in 20 of 30 (67%) patients and left ventricular ejection fraction improved in 15 of 15 (100%) patients with follow-up measurements. Medication failure was common. Focal AT resolved spontaneously after delivery in eight of nine (89%) patients treated with only medications. Automaticity was suggested by discrete electrograms at sites of origin and lack of reported inducibility and termination with programmed stimulation in all patients who underwent electrophysiology studies. There were nine cases of successful catheter ablation with zero fluoroscopy since 2010. CONCLUSIONS: Automaticity is the dominant mechanism for patients with maternal focal AT during pregnancy. Catheter ablation with zero fluoroscopy is an emerging therapy for medically refractory cases.

Documentation of shared decision making around primary prevention defibrillator implantations.

INTRODUCTION: Patients eligible for primary prevention implantable cardioverter-defibrillator (ICD) therapy are faced with a complex decision that needs a clear understanding of the risks and benefits of such an intervention. In this study, our goal was to explore the documentation of primary prevention ICD discussions in the electronic medical records (EMRs) of eligible patients. METHODS: In 1523 patients who met criteria for primary prevention ICD therapy between 2013 and 2015, we reviewed patient charts for ICD-related documentation: "mention" by physicians or "discussion" with patient/family. The attitude of the physician and the patient/family toward ICD therapy during discussions was categorized into negative, neutral, or positive preference. Patients were followed to the end-point of ICD implantation. RESULTS: Over a median follow-up of 442 days, 486 patients (32%) received an ICD. ICD was mentioned in the charts of 1105 (73%) patients, and a discussion with the patient/family about the risks and benefits of ICD was documented in 706 (46%) charts. On multivariable analyses, positive cardiologist (hazard ratio [HR]: 7.9, 95% confidence of intervals [CI]: 1.0-59.7, P < .05), electrophysiologist (HR: 7.7, 95% CI: 1.9-31.7, P < .001), and patient/family (HR: 9.9, 95% CI: 6.2-15.7, P < .001) preferences toward ICD therapy during the first documented ICD discussion were independently associated with ICD implantation. CONCLUSIONS: In a large cohort of patients eligible for primary prevention ICD therapy, a discussion with the patient/family about the risks and benefits of ICD implantation was documented in less than 50% of the charts. More consistent documentation of the shared decision making around ICD therapy is needed.

A new prediction model for ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy.

AIMS: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by ventricular arrhythmias (VAs) and sudden cardiac death (SCD). We aimed to develop a model for individualized prediction of incident VA/SCD in ARVC patients. METHODS AND RESULTS: Five hundred and twenty-eight patients with a definite diagnosis and no history of sustained VAs/SCD at baseline, aged 38.2 ± 15.5 years, 44.7% male, were enrolled from five registries in North America and Europe. Over 4.83 (interquartile range 2.44-9.33) years of follow-up, 146 (27.7%) experienced sustained VA, defined as SCD, aborted SCD, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator (ICD) therapy. A prediction model estimating annual VA risk was developed using Cox regression with internal validation. Eight potential predictors were pre-specified: age, sex, cardiac syncope in the prior 6 months, non-sustained ventricular tachycardia, number of premature ventricular complexes in 24 h, number of leads with T-wave inversion, and right and left ventricular ejection fractions (LVEFs). All except LVEF were retained in the final model. The model accurately distinguished patients with and without events, with an optimism-corrected C-index of 0.77 [95% confidence interval (CI) 0.73-0.81] and minimal over-optimism [calibration slope of 0.93 (95% CI 0.92-0.95)]. By decision curve analysis, the clinical benefit of the model was superior to a current consensus-based ICD placement algorithm with a 20.6% reduction of ICD placements with the same proportion of protected patients (P < 0.001). CONCLUSION: Using the largest cohort of patients with ARVC and no prior VA, a prediction model using readily available clinical parameters was devised to estimate VA risk and guide decisions regarding primary prevention ICDs (www.arvcrisk.com).

Non-vitamin K oral anticoagulants versus warfarin for left atrial appendage thrombus resolution in nonvalvular atrial fibrillation or flutter.

BACKGROUND: Non-vitamin K oral anticoagulants (NOACs) have emerged as alternatives to vitamin K antagonists in select situations. For left atrial (LA) appendage thrombus in nonvalvular atrial fibrillation (AF) or flutter, guidelines recommend oral anticoagulation (OAC) for at least 3 weeks prior to reassessment. Data comparing NOACs to warfarin in this scenario are scarce. METHODS: A retrospective study identified subjects with nonvalvular AF or flutter who were: a) noted to have LA thrombus detected on transesophageal echocardiography (TEE), b) previously not receiving long-term OAC; and c) evaluated for resolution of LA thrombus by follow-up TEE between 3 weeks to less than 1 year of the initial TEE. RESULTS: The study included 45 subjects with mean age 63.2 years, 69% male, 78% white race/ethnicity, 42% paroxysmal, and mean CHA2 DS2 -VASc score 3.4 ± 1.7. All LA thrombi were confined to the appendage. OAC received included apixaban (3), dabigatran (13), rivaroxaban (6), and warfarin (23), The median follow-up time to repeat TEE was 67 (interquartile range, 49-96) days. LA appendage thrombus resolution rates were 76% for the entire cohort, 77% for NOACs, and 74% for warfarin. In univariable logistic regression analysis, LA appendage thrombus resolution was similar for NOACs when compared to warfarin (odds ratio, 1.20; 95% confidence interval, 0.31-4.69; P = .79). CONCLUSIONS: In patients nonvalvular AF or flutter who were OAC naïve at the time of diagnosis with LA appendage thrombus, complete resolution was similar between NOACs and warfarin.

Implantable cardioverter-defibrillator therapy in device recipients who survived a cardiac arrest associated with a reversible cause.

BACKGROUND: Guideline recommendations for implantable cardioverter-defibrillators (ICD) for secondary prevention of sudden cardiac arrest (SCA) have excluded patients with reversible causes. We previously demonstrated mortality benefit with the ICD in survivors of SCA associated with reversible causes other than myocardial infarction (MI) or ischemia treated with coronary revascularization. In the current study, we examined the incidence of ICD therapy in patients with SCA related to reversible causes. METHODS: Data were collected for all patients over the age of 18 years who had survived to hospital discharge after SCA between 2002 and 2012. ICD recipients with reversible causes were divided into 2 groups based on their reversible etiology of SCA: MI + ICD (n = 132) and non-MI + ICD (n = 75). Delivered ICD therapy was examined. RESULTS: Over a follow-up period of 3.8 ± 3.1 years, more patients without MI/ischemia who received an ICD experienced appropriate (adjusted HR, 3.96; 95% CI, 1.32-11.84) but not inappropriate (adjusted HR, 0.65; 95% CI, 0.14-2.97) ICD therapy compared with patients without MI/ischemia. The proportion of patients receiving appropriate (P = 0.012) but not inappropriate (P = 0.80) ICD therapy was also higher in the non-MI + ICD compared with the MI + ICD group. CONCLUSION: We show higher rates of appropriate ICD therapy in survivors of SCA associated with reversible causes other than MI/ischemia. This finding, in conjunction with the previously demonstrated lower all-cause mortality noted in the presence of an ICD in SCA survivors with reversible etiology other than MI/ischemia, further supports consideration of ICD implantation in this population.

Arrhythmic outcome of arrhythmogenic right ventricular cardiomyopathy patients without implantable defibrillators.

BACKGROUND: Implantable defibrillators (ICD) are an important therapy for arrhythmogenic right ventricular cardiomyopathy (ARVC) patients at high risk of sudden death. Given the high appropriate ICD therapy rate, some have argued that the mere act of implanting an ICD inflates the malignant arrhythmia rate in ARVC. OBJECTIVE: To report the arrhythmic course of ARVC patients without ICDs at the fulfillment of the 2010 Task Force Criteria and explore predictors of malignant ventricular arrhythmias. METHODS: We included 131 definite ARVC patients (age 32 ± 15 years, male 39%, proband 50%) either without ICDs (N  =  47) or receiving an ICD at least 6 months after the fulfillment of the diagnostic criteria. The primary outcome was a composite of cardiac arrest (both resuscitated successfully and unsuccessfully) and sustained ventricular tachyarrhythmias (cycle length< 600 milliseconds, at least 30 seconds or requiring an intervention for termination). RESULTS: At the fulfillment of the diagnostic criteria, ICDs were not recommended to 59 (45%) patients and declined by 22 (17%) patients. Forty (31%) patients were not recognized as having ARVC by the treating physicians. Over 8 (interquartile interval: 3-12) years, 38 (29%) patients had primary outcomes (8 cardiac arrests [3 died] and 30 sustained ventricular arrhythmias) while not having ICDs. The 1-year and 5-year event-free survival was 92% and 72%. Spontaneous sustained ventricular arrhythmias, cardiac syncope, men, proband, and inducibility in electrophysiology study were significantly associated with the primary outcome. CONCLUSION: In a contemporary cohort, a considerable risk of malignant arrhythmias existed in ARVC when ICDs were not implanted.

Derivation and validation of a new score to predict long-term survival after sudden cardiac arrest.

BACKGROUND: There is insufficient information about the long-term prognosis of sudden cardiac arrest (SCA) survivors. We therefore derived a clinical score (Sudden Cardiac Arrest-mortality score, SCA-MS) that predicts long-term mortality in patients surviving to hospital discharge and validated it in an independent cohort of SCA survivors. METHODS: A total of 1433 SCA survivors data were collected, who were discharged from the hospitals of the University of Pittsburgh Medical Center between 2002 and 2012. The overall cohort was randomly divided into two near equal cohorts used for the derivation and validation of the SCA-MS, respectively. RESULTS: The derivation cohort included 768 patients and identified serum potassium level>4.2 mg/dL at admission, the presence of atrial fibrillation at any time during the index hospitalization, and the presence of asystole or pulseless electrical activity as the initial documented rhythm as independent predictors of long-term mortality. Based on the multivariable modeling result, one point was assigned to each one of these variables to create the SCA-MS that ranged from 0 to 3. In the validation cohort, the SCA-MS was predictive of long-term mortality (hazards ratio = 1.69, 95% confidence interval 1.50-1.91, P < 0.001) per 1-point increment in the SCA-MS. CONCLUSIONS: We describe a new clinical score that predicts long-term survival after SCA based on serum potassium levels at the admission, presence of atrial fibrillation, and documented rhythm of SCA.

Baseline Characteristics Predict the Presence of Amyloid on Endomyocardial Biopsy.

BACKGROUND: Recent studies have suggested a high prevalence of cardiac amyloidosis (CAm) in heart failure (HF) patients. CAm might be underdiagnosed owing to low clinical suspicion. METHODS AND RESULTS: We performed retrospective analysis of 259 patients with HF and ejection fraction (EF) ≥50% referred for endomyocardial biopsy. Seventy-three (28%) had CAm. Multivariable independent predictors of CAm were identified. Over a mean follow-up of 2.6 ± 3.3 years, CAm patients had worse survival than those without (1.5 y vs 6.3 y; log rank P < .0001). CONCLUSIONS: Clinicians should be suspicious of CAm in patients with EF 50%-75%, >50 years of age, BMI <30 kg/m2, peripheral neuropathy, Sokolow-Lyon index ≤15 mm, and septal wall thickness ≥1.4 cm.

Fibrofatty Changes: Incidence at Cardiac MR Imaging in Patients with Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy.

Purpose To determine the incidence of ventricular fatty replacement and late gadolinium enhancement (LGE) at cardiac magnetic resonance (MR) imaging in patients with arrhythmogenic right ventricular (RV) dysplasia/cardiomyopathy (ARVD/C) and the relationship of these findings to disease severity. Materials and Methods This was a retrospective institutional review board-approved HIPAA-compliant study. All subjects provided written informed consent. Seventy-six patients with ARVD/C were enrolled from 2002 to 2012. Quantitative and qualitative cardiac MR imaging analyses of the RV and the left ventricle (LV) were performed to determine cardiac MR imaging-specific Task Force Criteria (TFC) and non-TFC features (ARVD/C-type pattern of fatty infiltration and/or nonischemic pattern LGE). Patients were separated into four groups on the basis of cardiac MR imaging TFC: (a) patients with major cardiac MR imaging criteria, (b) patients with minor criteria, (c) patients with partial criteria, and (d) patients with no criterion. Continuous variables were compared by using the independent Student t test and analysis of variance. Categoric variables were compared by using the Fisher exact test. Results Of 76 patients (mean age, 34.2 years ± 14 [standard deviation]; 51.3% men), 42 met major cardiac MR imaging criteria, seven met minor criteria, seven met partial criteria, and 20 met no criterion. Most probands (36 [80.0%] of 45) met major or minor cardiac MR imaging criteria. Only 13 (41.9%) of 31 family members met any cardiac MR imaging criterion. The most common non-TFC MR imaging features were RV fatty infiltration (28.9%) and LV LGE (35.5%). Non-TFC cardiac MR imaging features were seen in 88.1% of subjects with major criteria, in 28.6% of those with minor criteria, in 71.4% of those with partial criteria, and in 10.0% of those with no criteria. Conclusion In this large cohort of patients with ARVD/C, non-TFC findings of ventricular fatty infiltration and LGE were frequent and were most often found in those who met major cardiac MR imaging criteria and in probands. (©) RSNA, 2016 Online supplemental material is available for this article.

Impact of genotype on clinical course in arrhythmogenic right ventricular dysplasia/cardiomyopathy-associated mutation carriers.

AIMS: We sought to determine the influence of genotype on clinical course and arrhythmic outcome among arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C)-associated mutation carriers. METHODS AND RESULTS: Pathogenic mutations in desmosomal and non-desmosomal genes were identified in 577 patients (241 families) from USA and Dutch ARVD/C cohorts. Patients with sudden cardiac death (SCD)/ventricular fibrillation (VF) at presentation (n = 36) were younger (median 23 vs. 36 years; P < 0.001) than those presenting with sustained monomorphic ventricular tachycardia (VT). Among 541 subjects presenting alive, over a mean follow-up of 6 ± 7 years, 12 (2%) patients died, 162 (30%) had sustained VT/VF, 78 (14%) manifested left ventricular dysfunction (EF < 55%), 28 (5%) experienced heart failure (HF), and 10 (2%) required cardiac transplantation. Patients (n = 22; 4%) with >1 mutation had significantly earlier occurrence of sustained VT/VF (mean age 28 ± 12 years), lower VT-/VF-free survival (P = 0.037), more frequent left ventricular dysfunction (29%), HF (19%) and cardiac transplantation (9%) when compared with those with only one mutation. Desmoplakin mutation carriers experienced more than four-fold occurrence of left ventricular dysfunction (40%) and HF (13%) than PKP2 carriers. Missense mutation carriers had similar death-/transplant-free survival and VT/VF penetrance (P = 0.137) when compared with those with truncating or splice site mutations. Men are more likely to be probands (P < 0.001), symptomatic (P < 0.001) and have earlier and more severe arrhythmic expression. CONCLUSIONS: Presentation with SCD/VF occurs at a significantly younger age when compared with sustained monomorphic VT. The genotype of ARVD/C mutation carriers impacts clinical course and disease expression. Male sex negatively modifies phenotypic expression.

Predictors of long-term outcomes in symptomatic hypertrophic obstructive cardiomyopathy patients undergoing surgical relief of left ventricular outflow tract obstruction.

BACKGROUND: We report the predictors of long-term outcomes of symptomatic hypertrophic cardiomyopathy patients undergoing surgical relief of left ventricular outflow tract obstruction. METHODS AND RESULTS: We studied 699 consecutive patients who have hypertrophic cardiomyopathy with severe symptomatic left ventricular outflow tract obstruction (47±11 years, 63% male) intractable to maximal medical therapy, who were referred to a tertiary hospital between January 1997 and December 2007 for the surgical relief of left ventricular outflow tract obstruction. We excluded patients <18 years of age, those with an ejection fraction <50%, those with hypertensive heart disease of the elderly, and those with more than mild aortic or mitral stenosis. Clinical, echocardiographic, and Holter data were recorded. A composite end point of death, appropriate internal cardioverter defibrillator discharges, resuscitated from sudden death, documented stroke, and admission for congestive heart failure was recorded. During a mean follow-up of 6.2±3 years, 86 patients (12%) met the composite end point with 30-day, 1-year, and 2-year event rates of 0.7%, 2.8%, and 4.7%, respectively. The hard event rate (death, defibrillator discharge, and resuscitated from sudden death) at 30 days, 1 year, and 2 years was 0%, 1.5%, and 3%, respectively. Stepwise multivariable analysis identified residual postoperative atrial fibrillation (hazard ratio, 2.12; confidence interval, 1.37-3.34; P=0.001) and increasing age (hazard ratio, 1.49; confidence interval, 1.22-1.82; P=0.001) as independent predictors of long-term composite outcomes. CONCLUSIONS: Symptomatic adult hypertrophic cardiomyopathy patients undergoing surgery for the relief of left ventricular outflow tract obstruction have low event rates during long-term follow-up; worse outcomes are predicted by increasing age and the presence of residual atrial fibrillation during follow-up.

Impact of Weight Gain on Cardiovascular Outcomes in Patients With Atrial Fibrillation.

BACKGROUND: The long-term impact of weight gain (WG) on cardiovascular outcomes among patients with atrial fibrillation (AF) is unclear. METHODS AND RESULTS: We studied 62 871 (mean age, 72±12, 43% women) adult patients with AF evaluated at the University of Pittsburgh Medical Center between January 1, 2010, and May 13, 2021. Serial body mass index, risk factors, comorbidities, and subsequent death and hospitalization were ascertained and stratified according to percentage WG (≥0% to <5%, ≥5% to <10%, and ≥10%). Over 4.9±3.19 years of follow-up, 27 114 (43%) patients gained weight (61%, ≥0% to <5%; 23%, ≥5% to <10%; 16%, ≥10%). Patients with progressive WG were incrementally younger (P<0.001) women (40%, 42%, and 47%) with lower median household income (P=0.002) and active smoking (8%, 13% and 13%), and they were less likely to be on a non-vitamin K oral anticoagulant (39%, 37%, and 32%). WG was incrementally associated with a significant increase in risk of hospitalization for AF (≥10% WG; hazard ratio [HR], 1.2 [95% CI, 1.2-1.3]; P<0.0001), heart failure (≥10% WG; HR, 1.44 [95% CI, 1.3-1.6]; P<0.001; ≥5% to <10% WG; HR, 1.17 [95% CI, 1.1-1.2]; P<0.001), myocardial infarction (≥10% WG; HR, 1.2 [95% CI, 1.3-1.6]; P<0.001) and all-cause stroke (4.2%, 4.3%, and 5.6%) despite significantly lower mean CHADS2Vasc score (2.9±1.7, 2.7±1.6, and 2.7±1.7). Patients with more WG were significantly more likely to receive cardiac and electrophysiologic interventions. CONCLUSIONS: Among patients with AF, WG is incrementally associated with increased hospitalization for cardiovascular causes, particularly heart failure, stroke, myocardial infarction, and AF.

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.

Mortality, Hospitalization, and Cardiac Interventions in Patients With Atrial Fibrillation Aged <65 Years.

BACKGROUND: The risk factor (RF) burden, clinical course, and long-term outcome among patients with atrial fibrillation (AF) aged <65 years is unclear. METHODS: Adult (n=67 221; mean age, 72.4±12.3 years; and 45% women) patients with AF evaluated at the University of Pittsburgh Medical Center between January 2010 and December 2019 were studied. Hospital system-wide electronic health records and administrative data were utilized to ascertain RFs, comorbidities, and subsequent hospitalization and cardiac interventions. The association of AF with all-cause mortality among those aged <65 years was analyzed using an internal contemporary cohort of patients without AF (n=918 073). RESULTS: Nearly one-quarter (n=17 335) of the cohort was aged <65 years (32% women) with considerable cardiovascular RFs (current smoker, 16%; mean body mass index, 33.0±8.3; hypertension, 55%; diabetes, 21%; heart failure, 20%; coronary artery disease, 19%; and prior ischemic stroke, 6%) and comorbidity burden (chronic obstructive pulmonary disease, 11%; obstructive sleep apnea, 18%; and chronic kidney disease, 1.3%). Over mean follow-up of >5 years, 2084 (6.7%, <50 years; 13%, 50-65 years) patients died. The proportion of patients with >1 hospitalization for myocardial infarction, heart failure, and stroke was 1.3%, 4.8%, and 1.1% for those aged <50 years and 2.2%, 7.4%, and 1.1% for the 50- to 65-year subgroup, respectively. Multiple cardiac and noncardiac RFs were associated with increased mortality in younger patients with AF with heart failure and hypertension demonstrating significant age-related interaction (P=0.007 and P=0.013, respectively). Patients with AF aged <65 years experienced significantly worse survival compared with comorbidity-adjusted patients without AF (men aged <50 years and hazard ratio, 1.5 [95% CI, 1.24-1.79]; 50-65 years and hazard ratio, 1.3 [95% CI, 1.26-1.43]; women aged <50 years and hazard ratio, 2.4 [95% CI, 1.82-3.16]; 50-65 years and hazard ratio, 1.7 [95% CI, 1.6-1.92]). CONCLUSIONS: Patients with AF aged <65 years have significant comorbidity burden and considerable long-term mortality. They are also at a significantly increased risk of hospitalization for heart failure, stroke, and myocardial infarction. These patients warrant an aggressive focus on RF and comorbidity evaluation and management.