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.

Cardiovascular Hospitalizations and Resource Use Following Atrial Fibrillation Ablation.

Background Over the next few years, atrial fibrillation (AF)-related morbidity and costs will increase significantly. Thus, it is prudent to examine the impact of AF treatment on health care resource use. This study examined the impact of AF ablation on hospitalization, length of stay, and resource use for patients undergoing AF ablation in a multihospital system. Methods and Results In an observational analysis, outcomes of total, cardiovascular, and AF hospitalizations, emergency department visits, and length of stay were compared for 3417 patients between 12 months before and 24 months following AF ablation. Use of electrical cardioversions and antiarrhythmic use were also compared 1 year before to 2 years after AF ablation. There were fewer total (0.7±1.3 versus 0.3±0.7; P<0.001), cardiovascular (0.7±1.2 versus 0.2±0.6; P<0.001), and AF (0.6±1.1 versus 0.1±0.3; P<0.001) hospitalizations and emergency department visits (0.8±2.1 versus 0.4±0.9; P<0.001) per patient-year for the 2 years following AF ablation compared with 1 year before. Average length of stay per patient-year (1.4±7.9 versus 3.6±5.3 days; P<0.0001), the percentage of patients on antiarrhythmic therapy (21.2% versus 58.5%; P<0.0001), and those undergoing electrical cardioversions (16.1% versus 28.1%; P<0.0001) were lower 2 years following AF ablation versus 1 year before. Conclusions We noted a decrease in total, cardiovascular, and AF hospitalizations and health care resource use during the 2-year period after index AF ablation, compared with the 1 year before. AF ablation may portend a decline in patient morbidity and health care costs.

Targeted left ventricular lead positioning to the site of latest activation in cardiac resynchronization therapy: a systematic review and meta-analysis.

AIMS: Several studies have evaluated the use of electrically- or imaging-guided left ventricular (LV) lead placement in cardiac resynchronization therapy (CRT) recipients. We aimed to assess evidence for a guided strategy that targets LV lead position to the site of latest LV activation. METHODS AND RESULTS: A systematic review and meta-analysis was performed for randomized controlled trials (RCTs) until March 2023 that evaluated electrically- or imaging-guided LV lead positioning on clinical and echocardiographic outcomes. The primary endpoint was a composite of all-cause mortality and heart failure hospitalization, and secondary endpoints were quality of life, 6-min walk test (6MWT), QRS duration, LV end-systolic volume, and LV ejection fraction. We included eight RCTs that comprised 1323 patients. Six RCTs compared guided strategy (n = 638) to routine (n = 468), and two RCTs compared different guiding strategies head-to-head: electrically- (n = 111) vs. imaging-guided (n = 106). Compared to routine, a guided strategy did not significantly reduce the risk of the primary endpoint after 12-24 (RR 0.83, 95% CI 0.52-1.33) months. A guided strategy was associated with slight improvement in 6MWT distance after 6 months of follow-up of absolute 18 (95% CI 6-30) m between groups, but not in remaining secondary endpoints. None of the secondary endpoints differed between the guided strategies. CONCLUSION: In this study, a CRT implantation strategy that targets the latest LV activation did not improve survival or reduce heart failure hospitalizations.

Relative Contribution of Atrial Fibrillation to Outcomes of Patients With Cardiomyopathy Based on Severity of Left Ventricular Dysfunction.

In patients with left ventricular (LV) dysfunction, the risk of death or heart failure hospitalizations (HFHs) increases with worsening ejection fraction (EF). Whether the relative contribution of atrial fibrillation (AF) to outcomes is more pronounced in patients with worse EF is not confirmed. The present study aimed to investigate the relative influence of AF on the outcome of cardiomyopathy patients by severity of LV dysfunction. In this observational study, data from 18,003 patients with EF ≤50% seen at a large academic institution between 2011 and 2017 were analyzed. Patients were stratified by EF quartiles (EF<25%, 25%≤EF<35%, 35%≤EF<40%, and EF≥40%, for quartiles 1, 2, 3, and 4, respectively). and followed to the end point of death or HFH. Outcomes of AF versus non-AF patients were compared within each EF quartile. During a median follow-up of 3.35 years, 8,037 patients (45%) died and 7,271 (40%) had at least 1 HFH. Rates of HFH and all-cause mortality increased as EF decreased. The hazard ratios (HRs) of death or HFH for AF versus non-AF patients increased steadily with increasing EF (HR of 1.22, 1.27, 1.45, 1.50 for quartiles 1, 2, 3, and 4, respectively, p = 0.045) driven primarily by the risk of HFH (HR of 1.26, 1.45, 1.59, 1.69 for quartiles 1, 2, 3, and 4, respectively, p = 0.045). In conclusion, in patients with LV dysfunction, the detrimental influence of AF on the risk of HFH is more pronounced in those with more preserved EF. Mitigation strategies for AF with the goal of decreasing HFH may be more impactful in patients with more preserved LV function.

Ventricular conduction abnormality in patients with mild to moderate cardiomyopathy.

BACKGROUND: In mild-to-moderate cardiomyopathy, cardiac resynchronization therapy (CRT) is indicated in patients with high burden of right ventricular pacing but not in those with intrinsic ventricular conduction abnormalities. HYPOTHESIS: We hypothesized that CRT positively impacts outcomes of patients with intrinsic ventricular conduction delay and left ventricular ejection fraction (LVEF) of 36%-50%. METHODS: Of 18 003 patients with LVEF ≤ 50%, 5966 (33%) patients had mild-to-moderate cardiomyopathy, of whom 1741 (29%) have a QRS duration ≥120 ms. Patients were followed to the endpoints of death and heart failure (HF) hospitalization. Outcomes were compared between patients with narrow versus wide QRS. RESULTS: Of the 1741 patients with mild-to-moderate cardiomyopathy and wide QRS duration, only 68 (4%) were implanted with a CRT device. Over a median follow-up of 3.35 years, 849 (51%) died and 1004 (58%) had a HF hospitalization. The adjusted risk of death (hazard ratio (HR) = 1.11, p = 0.046) and of death or HF hospitalization (HR = 1.10, p = 0.037) were significantly higher in patients with wide versus narrow QRS duration. In patients with wide QRS complex, CRT was associated with reduction in the adjusted risk of death (HR = 0.47, p = 0.020) and of death or HF hospitalization (HR = 0.58, p = 0.008). CONCLUSIONS: Patients with mild-to-moderate cardiomyopathy and wide QRS duration are rarely implanted with CRT devices and have worse outcomes compared to those with narrow QRS. Randomized trials are needed to examine if CRT has salutary effects in this population.

Quality of Life and Type of Cardiac Resynchronization Therapy Device in Older Heart Failure Patients.

Background: Cardiac resynchronization therapy (CRT) improves quality of life (QOL) in heart failure (HF) patients with reduced ejection fraction. Clinicians may have difficulty choosing between CRT with a pacemaker (CRT-P) or a defibrillator (CRT-D) for older patients. CRT-P devices are smaller, have more battery longevity, are less prone to erosions or recalls, and do not deliver shocks. These factors may impact patients' QOL, but data on such comparisons are lacking. Objectives: We examined the impact of CRT-P versus CRT-D on the QOL of older (≥75 years) HF patients who qualified for implantable cardioverter defibrillator therapy. Settings/Subjects/Measurements: We enrolled 101 CRT recipients and assessed QOL at baseline and at six-month post-implant using the Short Form Health Survey (SF-36) and the Minnesota living with heart failure (MLHF) questionnaires. Results: The average age of enrolled patients was 81 years, 27% were women, and 40 received a CRT-P device. After adjusting for baseline QOL score, age, sex, HF functional class, and the occurrence of adverse events, we found no significant differences in QOL outcomes between CRT-P and CRT-D recipients based on either the subscales or the composite scores for the SF-36 or MLHF questionnaires at six-months post-implantation. Conclusions: Older CRT-P and CRT-D recipients report comparable QOL scores six months after device implantation. Larger cohort studies with longer follow-up are needed to accurately assess potential QOL differences between CRT-D and CRT-P recipients to guide clinical decision making and ensure the right balance of risk versus benefit in these patients. Appropriate goals-of-care discussions are the corner stone of clinical decision making regarding defibrillator therapy. As such, even as the data stand at present, there is a need for more deliberate referral of older patients with HF to Palliative Care Specialists, or to Cardiologists trained in Palliative Care Medicine. clinicaltrials.gov listing: NCT03031847.

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.

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.

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.

Sex-specific clinical outcomes after cardiac resynchronization therapy in left bundle branch block-associated idiopathic nonischemic cardiomyopathy: A NEOLITH II substudy.

BACKGROUND: Sex differences in clinical outcomes for left bundle branch block (LBBB)-associated idiopathic nonischemic cardiomyopathy (NICM) after cardiac resynchronization therapy (CRT) are not well described. METHODS: A retrospective cohort study at an academic medical center included subjects with LBBB-associated idiopathic NICM who received CRT. Cox regression analyses estimated the hazard ratios (HRs) between sex and clinical outcomes. RESULTS: In 123 total subjects (mean age 62 years, mean initial left ventricular ejection fraction 22.8%, 76% New York Heart Association class III, and 98% CRT-defibrillators), 55 (45%) were men and 68 (55%) were women. The median follow-up time after CRT was 72.4 months. Similar risk for adverse clinical events (heart failure hospitalization, appropriate implantable cardioverter-defibrillator shock, appropriate antitachycardia pacing therapy, ventricular assist device implantation, heart transplantation, and death) was observed between men and women (HR, 1.20; 95% confidence interval [CI] 0.57-2.51; p = 0.63). This persisted in multivariable analyses. Men and women had similar risk for all-cause mortality in univariable analysis, but men had higher risk in the final multivariable model that adjusted for age at diagnosis, QRS duration, and left ventricular end-diastolic dimension index (HR, 4.55; 95% CI, 1.26-16.39; p = 0.02). The estimated 5-year mortality was 9.5% for men and 6.9% for women. CONCLUSIONS: In LBBB-associated idiopathic NICM, men have higher risk for all-cause mortality after CRT when compared to women.

Myocardial recovery after cardiac resynchronization therapy in left bundle branch block-associated idiopathic nonischemic cardiomyopathy: A NEOLITH II substudy.

BACKGROUND: Baseline predictors of myocardial recovery after cardiac resynchronization therapy (CRT) in left bundle branch block (LBBB)-associated idiopathic nonischemic cardiomyopathy (NICM) are unknown. METHODS: A retrospective study included subjects with idiopathic NICM, left ventricular ejection fraction (LVEF) ≤35%, and LBBB. Myocardial recovery was defined as post-CRT LVEF ≥50%. Logistic regression analyses described associations between baseline characteristics and myocardial recovery. Cox regression analyses estimated the hazard ratio (HR) between myocardial recovery status and adverse clinical events. RESULTS: In 105 subjects (mean age 61 years, 44% male, mean initial LVEF 22.6% ± 6.6%, 81% New York Heart Association class III, and 98% CRT-defibrillators), myocardial recovery after CRT was observed in 56 (54%) subjects. Hypertension, heart rate, and serum blood urea nitrogen (BUN) had negative associations with myocardial recovery in univariable analyses. These associations persisted in multivariable analysis: hypertension (odds ratio (OR), 0.40; 95% confidence interval (CI), 0.17-0.95; p = 0.04), heart rate (OR per 10 bpm, 0.69; 95% CI, 0.48-0.997; p = 0.048), and serum BUN (OR per 1 mg/dl, 0.94; 95% CI, 0.88-0.99; p = 0.04). Subjects with post-CRT LVEF ≥50%, when compared to <50%, had lower risk for adverse clinical events (heart failure hospitalization, appropriate implantable cardioverter-defibrillator shock, appropriate anti-tachycardia pacing therapy, ventricular assist device implantation, heart transplantation, and death) over a median follow-up of 75.9 months (HR, 0.38; 95% CI, 0.16-0.88; p = 0.02). CONCLUSION: In LBBB-associated idiopathic NICM, myocardial recovery after CRT was associated with absence of hypertension, lower heart rate, and lower serum BUN. Those with myocardial recovery had fewer adverse clinical events.