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Atrial fibrillation (AF) and heart failure (HF)-specifically, heart failure with reduced ejection fraction (HFrEF)-often coexist, and each contributes to the propagation of the other. This relationship extends from the mechanistic and physiological to clinical syndromes, quality of life, and long-term cardiovascular outcomes. The risk factors for AF and HF overlap and create a critical opportunity to prevent adverse outcomes among patients at greatest risk for either condition. Increasing recognition of the linkages between AF and HF have led to widespread interest in designing diagnostic, predictive, and interventional strategies targeting all aspects of disease, from identifying genetic predisposition to addressing social determinants of health. Advances across this spectrum culminated in updated multisociety guidelines for management of AF, which includes specific consideration of comorbid AF and HF. This review expands on these guidelines by further highlighting relevant clinical trial findings and providing additional context for the evolving recommendations for management in this important and growing population., Competing Interests: Funding Support and Author Disclosures Dr Zeitler has received salary support from the National Institutes of Health (NIH) (1P20GM148278-01) and nonfinancial research support from Boston Scientific, Biosense Webster, and Sanofi; she has received consulting and speaker fees from Abbott, Biosense Webster, Medtronic, and Sanofi. Dr Johnson has received salary support from the NIH/NHLBI (#K23HL165110) and consulting and speaker fees from Edwards Lifesciences and Sanofi. Dr Steinberg has received salary support from the NIH/NHLBI (#K23HL143156, #R56HL168264, #R21HL172288) and AHA/PCORI (18SFRN34110489) and research support from Abbott, Cardiva, Sanofi, and AltaThera; he has received consulting fees from Sanofi, InCarda, Milestone, Pfizer, and AltaThera. All other authors have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Ventricular assist device (VAD) patients often experience infections, which increase the risk of stroke and mortality. Using the definitions of the International Society for Heart and Lung Transplantation (ISHLT), we have characterized differences in clinical outcomes for categories of infection: VAD-specific (e.g., pump component related); VAD-related (e.g., bloodstream infection, BSI); and non-VAD infections (e.g., pneumonia)., Methods: Querying of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) identified 16,597 continuous-flow VAD recipients. Categories of infection were tested in multivariate models to determine the risk of stroke and death., Results: After implant, 7,046 patients (42%) developed an infection at a median of 69 (interquartile range 12 to 272) days. A majority were non-VAD infections (49%), followed by VAD-related (26%) and VAD-specific infections (25%). BSIs were the most common form of VAD-related infection (92%), and the majority (59%) had no associated infection, that is, idiopathic bacteremia. Internal pump component infections were rare (0.003 event per patient-year [EPPY]). Infected VAD patients had a higher prevalence of stroke compared to patients without an infection (18% vs 11%, p < 0.001). The lowest stroke rate occurred after a VAD-specific infection (0.11 EPPY) compared with VAD-related (0.17 EPPY) and non-VAD infections (0.15 EPPY, p < 0.001). Hemorrhagic strokes were more common than ischemic strokes in all infection groups and highest after a VAD-related infection (0.13 EPPY). One-year survival after an infection was 87% in VAD-specific infections, as compared with VAD-related (71%) and non-VAD infections (72%, p < 0.001)., Conclusions: The ISHLT categorization of VAD infections unveils notable differences in associated risk of stroke and mortality. A re-assessment of transplant prioritization for eligible infected VAD patients may be useful to increase transplant-related survival benefit., (Copyright © 2019 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Large randomized clinical trials (RCT) supporting guidelines for the management of heart failure with reduced ejection fraction (HFrEF) have typically excluded patients with advanced chronic kidney disease (CKD). Patients with concomitant advanced CKD and HFrEF experience poor cardiovascular outcomes and mortality relative to either disease in isolation and have been shown to consistently receive lower rates of HFrEF guideline-directed medical therapy (GDMT). This review evaluated recent evidence for the use of GDMT in patients with HFrEF and advanced CKD approaching dialysis from RCTs and observational cohorts. The authors also discuss the limitations and challenges inherent in the evidence for GDMT in this population, and offer guidance to clinicians for proper clinical use and future research directions., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

There is increasing recognition of the relationship between diabetes and heart failure (HF). Comorbid diabetes is associated with worse outcomes in patients with HF, and death from HF forms a large burden of mortality among patients with diabetes and atherosclerotic cardiovascular disease. However, there is evidence of harm relating to the risk of HF outcomes from several antihyperglycemic therapies. The absence of well-powered randomized controlled studies has resulted in significant treatment variations in the glycemic management in patients with coexisting diabetes and HF. However, there is emerging evidence from recent clinical trials suggesting that sodium-glucose-co-transporter-2 inhibitors may be used as a therapy to improve HF outcomes. In order to understand the current state of knowledge, we reviewed the evolving evidence of antihyperglycemic therapies and present strategies to optimize these therapies in patients with diabetes and HF. This analysis is based on discussions among scientists, clinical trialists, industry sponsors, and regulatory representatives who attended the 12th Global Cardiovascular Clinical Trialists Forum, Washington, DC, December 1 to 3, 2016., (Copyright © 2018. Published by Elsevier Inc.)

Background: Pre-transplant amiodarone use has been postulated as a risk factor for morbidity and mortality after orthotopic heart transplantation (OHT). We assessed pre-OHT amiodarone use and tested the hypothesis that it is associated with impaired post-OHT outcomes., Methods: We performed a retrospective cohort analysis of adult OHT recipients from the registry of the International Society for Heart and Lung Transplantation (ISHLT). All patients had been transplanted between 2005 and 2013 and were stratified by pre-OHT amiodarone use. We derived propensity scores using logistic regression with amiodarone use as the dependent variable, and assessed the associations between amiodarone use and outcomes with Kaplan-Meier analysis after matching patients 1:1 based on propensity score, and with Cox regression with adjustment for propensity score., Results: Of the 14,944 OHT patients in the study cohort, 32% (N = 4,752) received pre-OHT amiodarone. Amiodarone use was higher in recent years (29% in 2005 to 2007, 32% in 2008 to 2010, 35% in 2011 to 2013). Amiodarone-treated patients were older and more frequently had a history of sudden cardiac death (27% vs 13%) and pre-OHT mechanical circulatory support. Key donor characteristics and allograft ischemia times were similar between groups. In propensity-matched analyses, amiodarone-treated patients had higher rates of cardiac reoperation (15% vs 13%) and permanent pacemaker (5% vs 3%) after OHT and before discharge. Amiodarone-treated patients also had higher 1-year mortality (hazard ratio 1.15, 95% confidence interval 1.02 to 1.30), but the risks of early graft failure, retransplantation and rehospitalization were similar between groups., Conclusions: Amiodarone use before OHT was independently associated with increased 1-year mortality. The need for amiodarone therapy should be carefully and continuously assessed in patients awaiting OHT., (Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study evaluated the prevalence, profile, and prognosis of severe obesity in a large contemporary acute heart failure (AHF) population., Background: Better prognosis has been reported for obese heart failure (HF) patients than nonobese HF patients, but in other cardiovascular populations, this effect has not been demonstrated for severely obese patients., Methods: A cohort of 795 participants with body mass index (BMI) measured at time of admission and complete follow-up were identified from enrollment in 3 contemporary AHF trials (DOSE [Diuretic Strategies Optimization Evaluation], CARRESS-HF [Cardiorenal Rescue Study in Acute Decompensated Heart Failure], and ROSE [Renal Optimization Strategies Evaluation in Acute Heart Failure]). Patients were divided into 4 BMI categories according to standard World Health Organization criteria, as follows: normal weight: 18.5 to 25 kg/m 2 [n = 128]; overweight: 25 to 29.9 kg/m 2 [n = 209]; mild-to-moderate obese: 30 to 39.9 kg/m 2 [n = 301]; and severely obese: ≥40 kg/m 2 [n = 157]). The relationship between BMI and 60-day composite outcome (death, rehospitalization, or unscheduled provider visit) was investigated., Results: Patients with severe obesity (19.7%) were younger, more often female, hypertensive, diabetic, and more likely to have higher blood pressures and left ventricular ejection fraction, and lower N-terminal pro-B-type natriuretic peptide and troponin I levels than other BMI category patients. Following admission for AHF, patients with normal weight showed the highest risk of 60-day composite outcome, followed by patients who were severely obese. Overweight and mild-moderately obese patients showed lowest risk., Conclusions: Nearly one-fifth of AHF patients enrolled in contemporary randomized clinical trials are severely obese. A U-shaped curve for short-term prognosis according to BMI is seen in AHF. These findings may help to better inform both HF clinical care and future clinical trial planning., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Opioid users experience increased incidence of infection, which may be partially attributable to both direct opiate-immune interactions and conditioned immune responses. Previous studies have investigated the neural circuitry governing opioid conditioned immune responses, but work remains to elucidate the mechanisms mediating this effect. Our laboratory has previously shown that hippocampal IL-1 signaling, specifically, is required for the expression of heroin conditioned immunosuppression following learning. The current studies were designed to further characterize the role of hippocampal IL-1 in this phenomenon by manipulating IL-1 during learning. Experiment 1 tested whether hippocampal IL-1 is also required for the acquisition of heroin conditioned immunosuppression, while Experiment 2 tested whether hippocampal IL-1 is required for the expression of unconditioned heroin immunosuppression. We found that blocking IL-1 signaling in the dorsal hippocampus with IL-1RA during each conditioning session, but not on interspersed non-conditioning days, significantly attenuated the acquisition of heroin conditioned immunosuppression. Strikingly, we found that the same IL-1RA treatment did not alter unconditioned immunosuppression to a single dose of heroin. Thus, IL-1 signaling is not a critical component of the response to heroin but rather may play a role in the formation of the association between heroin and the context. Collectively, these studies suggest that IL-1 signaling, in addition to being involved in the expression of a heroin conditioned immune response, is also involved in the acquisition of this effect. Importantly, this effect is likely not due to blocking the response to the unconditioned stimulus since IL-1RA did not affect heroin's immunosuppressive effects., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Heart transplantation is increasing in patients with adult congenital heart disease (ACHD). In this population, the association of pulmonary hypertension (PH) with post-transplant outcomes is not well-defined., Methods: Using data from the United Network for Organ Sharing database (1987 to 2014), we identified ACHD patients listed for heart transplantation, and examined survival between those with and without PH (pre-transplant PH defined as transpulmonary pressure gradient >12 mm Hg)., Results: Among 983 ACHD patients, 216 (22%) had PH. At time of listing, PH patients had a transpulmonary pressure gradient of 17.0 mm Hg vs 6.0 mm Hg (p < 0.01) in the no-PH group. Although left ventricular assist device (LVAD) use was infrequent, 3.1% of PH patients were treated with an LVAD versus 6.8% of the no-PH patients. Days from listing to transplant, days from listing to death on the waitlist and length of post-transplant hospitalization were not significantly different between the PH and no-PH groups. However, PH was associated with higher waitlist mortality (HR 1.73, CI 1.25 to 2.41). Pre-transplant PH was not associated with post-transplant mortality at 30 days (HR 0.51, CI 0.23 to 1.13), 1 year (HR 0.68, 95% CI 0.40 to 1.18) or 5 years (HR 0.84, 95% CI 0.55 to 1.29)., Conclusions: PH is common among ACHD patients listed for transplant and is associated with increased waitlist mortality. Conversely, PH was not associated with worse survival after transplant. Bridge-to-transplant LVAD therapy was uncommon in this ACHD population., (Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: With increasing age of patients with heart failure, it is important to understand the potential role for orthotopic heart transplant (OHT) in elderly patients. We examined recipient and donor characteristics and long-term outcomes of older recipients of OHT in the United States., Methods: Using the United Network for Organ Sharing database, we identified OHT recipients from the years 1987-2014 and stratified them by age 18-59 years old, 60-69 years old, and ≥70 years old. We compared baseline characteristics of recipients and donors and assessed outcomes across groups., Results: During this period, 50,432 patients underwent OHT; 71.8% (n = 36,190) were 18-59 years old, 26.8% (n = 13,527) were 60-69 years old, and 1.4% (n = 715) were ≥70 years old. Comparing the ≥70 years old group and 60-69 years old group, older patients had higher rates of ischemic etiology (53.6% vs 44.9%) and baseline renal dysfunction (61.4% vs 56.4%) and at the time of OHT were less likely to be currently hospitalized (45.0% vs 50.9%) or supported with left ventricular assist device therapy (21.0% vs 28.3%). Older recipients received organs from older donors (median age 36 years old vs 30 years old) who were more likely to have diabetes and substance use. After OHT, the median length of stay was similar between groups. At 1 year, of patients alive, patients ≥70 years old had fewer rejection episodes (17.8%) compared with patients 60-69 years old (29.5%). The 5-year mortality was 26.9% for recipients 18-59 years old, 29.3% for recipients 60-69 years old, and 30.8% for recipients ≥70 years old., Conclusions: Despite advanced age and less ideal donors, OHT recipients in their 70s had similar outcomes to recipients in their 60s. Selected older patients should not routinely be excluded from consideration for OHT., (Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: We have previously demonstrated that high-dose chemoradiotherapy followed by resection for patients selected on the basis of mediastinal sterilization was feasible and resulted in excellent outcomes. This study was designed to determine the ability to intensify our prior approach utilizing hyperfractionated radiation and more aggressive consolidative chemotherapy., Methods: Patients with documented stage IIIA/B nonsmall-cell lung cancer, performance status 0 to 2, and adequate organ function were eligible. A phase I portion utilized escalating doses of carboplatin and vinorelbine, commencing with areas under the curve of 1 and 5 mg/m(2), respectively, and concurrent 69.6 Gy hyperfractionated radiotherapy. A phase II portion utilized the identical radiotherapy with carboplatin/vinorelbine at the maximum tolerated dose established in phase I. Patients for whom mediastinal nodal clearance was demonstrated underwent resection. All patients were to receive consolidation chemotherapy consisting of carboplatin/vinorelbine for three cycles, followed by docetaxel for three cycles. Prophylactic cranial irradiation was offered to patients after completion of therapy., Results: Forty-seven patients participated in the study (33 IIIA, 14 IIIB; 15 men, 32 women; median age, 56 years). The maximum tolerated dose for concurrent carboplatin/vinorelbine and hyperfractionated radiotherapy was established at areas under the curve of 1 and 10 mg/m(2), respectively. Twenty-eight patients completed trimodality treatment including surgery. Median survival time for the entire study cohort (n = 47) is 29.6 months, and it is 55.8 months for patients with mediastinal clearance who underwent resection (n = 28)., Conclusions: Surgical resection of locally advanced stage IIIA and IIIB nonsmall-cell lung cancer after induction hyperfractionated radiation and concurrent chemotherapy is safe and well tolerated. Whether this approach is superior to less aggressive therapy is uncertain and will require comparative studies.

Background: The primary goal of this study is to identify clinical variables associated with successful surgical treatment for hyperhidrosis and facial blushing., Methods: Six hundred eight thoracoscopic sympathicotomies were performed in 304 patients. Retrospective stratified analysis of patients after thoracoscopic sympathicotomy for hyperhidrosis or facial blushing and having completed follow-up of at least 6 months (n = 232) was performed. Preoperative and postoperative quality-of-life indices (range, 0 to 3) were used to measure impact of surgery, and comparisons were indexed to preoperative symptoms. Postoperative compensatory sweating was analyzed with respect to the level(s) of sympathetic chain division., Results: Thoracoscopic sympathicotomy was performed at level T2 alone in 5% of patients; levels T2 to T3 in 63% of patients; levels T3 to T4 in 3% of patients; levels T2 to T4 in 14% of patients; and more than three levels in 14% of patients. In hyperhidrosis patients, mean preoperative quality-of-life index was 2.0 and postoperative quality-of-life index was 0.4 (p < 0.001). Facial blushers had preoperative and postoperative quality-of-life index of 2.6 and 1.0, respectively. Significant compensatory sweating was seen in 33% patients overall and occurred in 29% of patients with palmar symptoms, 26% of axillary patients, and 42% of facial blushers. Significant compensatory sweating in relation to the level(s) of sympathetic chain division occurred in T2 alone, 45%; T2 to T3, 30%; T3 to T4, 14%; T2 to T4, 38%; and more than three levels, 49%., Conclusions: Significant improvement in quality of life can result from surgery for hyperhidrosis. However, the incidence of postoperative compensatory sweating may be dependent on the level of sympathicotomy performed. The choice of sympathicotomy level(s) should be directed toward reducing the incidence of significant compensatory sweating while simultaneously ensuring relief of primary preoperative symptoms.

Background: The purpose of this study is to evaluate the safety and efficacy of thoracoscopic sympathectomy for the treatment of hyperhidrosis, blushing, reflex sympathetic dystrophy, and digital ischemia., Methods: We conducted a retrospective review of 202 patients who underwent thoracoscopic sympathectomy at the University of Maryland from March 1992 to April 2003., Results: Three hundred ninety-seven procedures were performed on 202 patients (105 women, 97 men). Mean age was 29 years (range, 9 to 65). Indications for surgery included hyperhidrosis, facial blushing, digital ischemia, and reflex sympathetic dystrophy. Synchronous bilateral sympathectomies were performed in 194 patients; right side alone (n = 6); left side alone (n = 1); 1 patient had staged bilateral sympathectomies. Single incision with lung isolation technique was used. There was no mortality. Preoperative symptoms resolved completely or significantly improved in greater than 90% of patients. One patient with reflex sympathetic dystrophy recurred and 1 patient with hyperhidrosis complained of significant compensatory sweating. Compensatory sweating to a lesser degree occurred in approximately one third of patients. Complications included asymptomatic pleural effusion (n = 1), pneumothorax (n = 1), and reoperation for chylothorax that was identified early (n = 1). In 2 patients treated for facial blushing, Horner's syndrome developed postoperatively; 1 of them subsequently underwent blepharoplasty. In 3 patients, hyperesthesias developed at the incision., Conclusions: Thoracoscopic sympathectomy can be performed safely and with excellent results. Compensatory sweating is the main side effect, although significant complaints from this are rare. Horner's syndrome remains an extremely uncommon complication as a result of thoracoscopic sympathectomy at our institution.