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• Rates of U.S. donor heart acceptance declined significantly from 31% acceptance in quarter 3 of 2018 to 26% acceptance in quarter 3 of 2021. • Organs with certain high-risk features, such as anoxia or heavy alcohol use, are now more likely to be declined. • This aligns with several other practice changes following the 2018 donor allocation policy changes. • Wait times may be further reduced by continuing to understand which marginal donor hearts and donor risk factors can be used safely. Donor heart scarcity remains the fundamental barrier to increased transplant access. We examined whether 2018 United Network for Organ Sharing (UNOS) policy changes have had an impact on donor heart acceptance rates. We performed an interrupted time series analysis in UNOS to evaluate for abrupt changes in donor heart-acceptance rates associated with the new policy. All adult donor offers were evaluated between 2015 and 2021 (n = 66,654 donors). Donor volumes and transplants increased during this period, but the donor acceptance rate declined significantly from 31% in quarter 3 of 2018 to 26% acceptance in quarter 3 of 2021 (slope change -0.4% per quarter; P < 0.001). We identified 2 trends associated with this decline: (1) a growing number of donors with high-risk features, and (2) decreased acceptance of donors with certain high-risk features in the new allocation system. Heart transplant volumes have increased in recent years as a result of increased donor volumes, but donor heart acceptance rates began decreasing under the current allocation system. Changes in the donor pool and acceptance patterns for certain donor-risk features may explain this shift and warrant further evaluation to maximize donor heart use. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: There is paucity of data regarding durable left ventricular assist device (LVAD) outcomes in patients with chronic kidney disease (CKD) stages 3-5 and CKD stage 5 on dialysis (end-stage renal disease [ESRD]).Methods and Results: We conducted a retrospective study of Medicare beneficiaries with ESRD and a 5% sample of patients with CKD with an LVAD (2006-2018) to determine 1-year outcomes using the United States Renal Data System database. The LVAD implantation, comorbidities, and outcomes were identified using appropriate International Classification of Diseases, 9th and 10th edition codes. We identified 496 patients with CKD and 95 patients with ESRD who underwent LVAD implantation. The patients with ESRD were younger (59 years vs 66 years; P < .001), had more Blacks (40% vs 24.6%, P = .009), compared with the CKD group. The 1-year mortality (49.5% vs 30.9%, P < .001) and index mortality (27.4% vs 16.7%, P = .014) rates were higher for patients with ESRD. A subgroup analysis showed significantly higher mortality in ESRD vs CKD 3 (49.5% vs 30.2%, adjusted P = .009), but no significant difference in mortality between stage 3 vs 4/5 (30.2% vs 30.8%, adjusted P = .941). There was no significant difference in secondary outcomes (bleeding, stroke, and sepsis/infection) during follow-up between the 2 groups.Conclusions: Patients with ESRD undergoing LVAD implantation had significantly higher index and 1-year mortality rates compared with patients with CKD. [ABSTRACT FROM AUTHOR]

Background: Metolazone and intravenous (IV) chlorothiazide are commonly used diuretics for sequential nephron blockade (SNB) in patients with acute decompensated heart failure (ADHF). Previous studies suggest metolazone may be comparable with chlorothiazide in terms of efficacy and safety. The objective of this study was to determine whether IV chlorothiazide is superior to metolazone in increasing net urine output (UOP) of hospitalized patients with ADHF.Methods and Results: This retrospective cohort study included hospitalized patients with ADHF and evidence of loop diuretic resistance in a tertiary academic medical center. The primary end point was the change in net 24-hour UOP in patients treated with IV chlorothiazide compared with metolazone. The relative cost of chlorothiazide doses and metolazone doses administered during SNB was a notable secondary end point. The median change in net 24-hour UOP in the IV chlorothiazide group was -1481.9 mL (interquartile range -2696.0 to -641.0 mL) and -1780.0 mL (interquartile range -3084.5 to -853.5 mL) in the metolazone group (P = .05) across 220 hospital encounters. The median cost of chlorothiazide and metolazone doses used during SNB was $360 and $4, respectively (P < .01).Conclusions: Chlorothiazide was not superior to metolazone in changing the net 24-hour UOP of patients with ADHF and loop resistance. Preferential metolazone use in SNB is a potential cost-saving measure. [ABSTRACT FROM AUTHOR]

Background: The 2022 American College of Cardiology/American Heart Association/Heart Failure Society of America (AHA/ACC/HFSA) Guideline for the Management of Heart Failure replaces the 2013 ACCF/AHA Guideline for the Management of Heart Failure and the 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure. The 2022 guideline is intended to provide patient-centric recommendations for clinicians to prevent, diagnose and manage patients with heart failure.Methods: A comprehensive literature search was conducted from May 2020 to December 2020, encompassing studies, reviews and other evidence conducted in human subjects that were published in English from MEDLINE (PubMed), EMBASE, the Cochrane Collaboration, the Agency for Healthcare Research and Quality, and other relevant databases. Additional relevant clinical trials and research studies published through September 2021 were also considered. This guideline was harmonized with other American Heart Association/American College of Cardiology guidelines published through December 2021.Results and Conclusions: Heart failure remains a leading cause of morbidity and mortality globally. The 2022 heart failure guideline provides recommendations based on contemporary evidence for the treatment of these patients. The recommendations present an evidence-based approach to managing patients with heart failure, with the intent to improve quality of care and align with patients' interests. Many recommendations from the earlier heart failure guidelines have been updated with new evidence, and new recommendations have been created when supported by published data. Value statements are provided for certain treatments that have high-quality published economic analyses. [ABSTRACT FROM AUTHOR]

Heart failure (HF) fundamentally reflects an inability of the heart to provide adequate blood flow to the body without incurring the cost of increased cardiac filling pressures. This failure occurs first during the stressed state, but progresses until hemodynamic derangements become apparent at rest. As such, the measurement and interpretation of both resting and stressed hemodynamics serve an integral role in the practice of the HF clinician. In this review, we discuss conceptual and technical best practices in the performance and interpretation of both resting and invasive exercise hemodynamic catheterization, relate important pathophysiologic concepts to clinical care, and discuss updated, evidence-based applications of hemodynamics as they pertain to the full spectrum of HF conditions. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) frequently complicates heart failure (HF), and each is associated with lower overall health-related quality of life. We aimed to quantify the incremental burden of AF on the health-related quality of life of patients with HF in clinical practice.Methods and Results: We used data from the Utah mEVAL program to analyze patient-reported outcomes (PROs) among patients with HF with and without AF. The primary outcome was the HF-specific Kansas City Cardiomyopathy Questionnaire, with generic PROs as secondary outcomes. Among 1707 patients with HF, 36% had AF (n = 616). Those with HF and AF were older (mean age 69 years vs 58 years, P < .001), more likely to have prior stroke (29% vs 17%, P < .001) and ischemic cardiomyopathy (28% vs 23%, P = .01), but had similar ejection fractions (mean 44% each, P = .6). After adjustment, and compared with HF alone, HF with AF was associated with worse Kansas City Cardiomyopathy Questionnaire scores (adjusted mean difference -3.45, 95% confidence interval [CI] -6.24 to -0.65), and worse Patient-Reported Outcomes Measurement Information System physical function scores (adjusted mean difference -1.63, 95% CI -2.59 to -0.67). The difference in visual analog scale general health was borderline (adjusted mean difference -2.01, 95% CI -4.51 to 0.49), and Patient-Reported Outcomes Measurement Information System depression scores were similar (adjusted mean difference 0.54, 95% CI -0.48 to 1.57).Conclusions: AF complicates nearly one-third of HF cases, and patients with HF and AF are substantially older and sicker. After adjustment, AF was independently associated with worse disease-specific and overall health-related quality of life than HF alone. Whether maintaining sinus rhythm can improve the HF-related health status of patients with HF in clinical practice should be explored further. [ABSTRACT FROM AUTHOR]

Background: Heart failure-related cardiogenic shock (HF-CS) accounts for an increasing proportion of cases of CS in contemporary cardiac intensive care units. Whether the chronicity of HF identifies distinct clinical profiles of HF-CS is unknown.Methods and Results: We evaluated admissions to cardiac intensive care units for HF-CS in 28 centers using data from the Critical Care Cardiology Trials Network registry (2017-2020). HF-CS was defined as CS due to ventricular failure in the absence of acute myocardial infarction and was classified as de novo vs acute-on-chronic based on the absence or presence of a prior diagnosis of HF, respectively. Clinical features, resource use, and outcomes were compared among groups. Of 1405 admissions with HF-CS, 370 had de novo HF-CS (26.3%), and 1035 had acute-on-chronic HF-CS (73.7%). Patients with de novo HF-CS had a lower prevalence of hypertension, diabetes, coronary artery disease, atrial fibrillation, and chronic kidney disease (all P < 0.01). Median Sequential Organ Failure Assessment (SOFA) scores were higher in those with de novo HF-CS (8; 25th-75th: 5-11) vs acute-on-chronic HF-CS (6; 25th-75th: 4-9, P < 0.01), as was the proportion of Society of Cardiovascular Angiography and Intervention (SCAI) shock stage E (46.1% vs 26.1%, P < 0.01). After adjustment for clinical covariates and preceding cardiac arrest, the risk of in-hospital mortality was higher in patients with de novo HF-CS than in those with acute-on-chronic HF-CS (adjusted hazard ratio 1.36, 95% confidence interval 1.05-1.75, P = 0.02).Conclusions: Despite having fewer comorbidities, patients with de novo HF-CS had more severe shock presentations and worse in-hospital outcomes. Whether HF disease chronicity is associated with time-dependent compensatory adaptations, unique pathobiological features and responses to treatment in patients presenting with HF-CS warrants further investigation. [ABSTRACT FROM AUTHOR]

Heart failure with preserved ejection fraction (HFpEF) comprises approximately one-half of all diagnoses of heart failure. There is significant overlap of this clinical syndrome with chronic kidney disease (CKD), with many shared comorbid conditions. The presence of CKD in patients with HFpEF is one of the most powerful risk factors for adverse clinical outcomes, including death and heart failure hospitalization. The pathophysiology linking HFpEF and CKD remains unclear, but it is postulated to consist of numerous bidirectional pathways, including endothelial dysfunction, inflammation, obesity, insulin resistance, and impaired sodium handling. The diagnosis of HFpEF requires certain criteria to be satisfied, including signs and symptoms consistent with volume overload caused by structural or functional cardiac abnormalities and evidence of increased cardiac filling pressures. There are numerous overlapping metabolic clinical syndromes in patients with HFpEF and CKD that can serve as targets for intervention. With an increasing number of therapies available for HFpEF and CKD as well as for obesity and diabetes, improved recognition and diagnosis are paramount for appropriate management and improved clinical outcomes in patients with both HFpEF and CKD. [ABSTRACT FROM AUTHOR]

Reverse left ventricular (LV) remodeling and recovery of LV function are associated with improved clinical outcomes in patients with heart failure with reduced ejection fraction. A growing body of evidence suggests that even among patients who experience a complete normalization of LV ejection fraction, a significant proportion will develop recurrent LV dysfunction accompanied by recurrent heart failure events. This has led to intense interest in understanding how to manage patients with heart failure with recovered ejection fraction (HFrecEF). Because of the lack of a standard definition for HFrecEF, and the paucity of clinical data with respect to the natural history of HFrecEF patients, there are no current guidelines on how these patients should be followed up and managed. Accordingly, this JACC Scientific Expert Panel reviews the biology of reverse LV remodeling and the clinical course of patients with HFrecEF, as well as provides guidelines for defining, diagnosing, and managing patients with HFrecEF. [ABSTRACT FROM AUTHOR]

Sudden cardiac death (SCD) represents a major cause of death among patients with heart failure. Although scar-based, macroreentrant ventricular tachycardia/ventricular fibrillation is the primary etiology for SCD among patients with ischemic cardiomyopathy, a more diverse set of mechanisms and substrates is likely at play for the diverse group of patients characterized by nonischemic dilated cardiomyopathy (NICM). These causes may include scar-based reentry, but also neurohormonal stimulation (sympathetic, parasympathetic, renin-angiotensin-aldosterone), inflammation, and nonarrhythmic processes occurring in the context of a genetic predisposition. In addition to basic and translational science, observations from large randomized clinical trials of implantable cardioverter-defibrillators (ICDs) can also offer insight and support for specific mechanisms of SCD in these patients. This review will discuss the background of SCD in NICM, its potential mechanisms based on experimental and theoretical models, and the evidence for these mechanisms that can be derived from clinical trials of ICD therapy. [ABSTRACT FROM AUTHOR]

Background Patient-reported outcomes (PROs) quantify, from patients' perspectives, their symptoms, function, and quality of life. Our aim was to determine the feasibility of integrating PRO capture into routine clinical practice at a large heart failure (HF) clinic. Methods We examined the practicality of PRO completion at the time of clinic visit, the time required to complete the selected instruments, the completion rate, and the feasibility of immediate PRO scoring and integration of the results into the electronic health record (EHR). We deployed a computer program to capture PROs (Kansas City Cardiomyopathy Questionnaire, Patient-Reported Outcomes Measurement Information System) on a portable computer platform at the time of a clinic visit. An automated algorithm identified patients scheduled for appointments at the HF clinic at registration, provided a portable tablet computer with which to complete the appropriate PRO instruments and then scored and immediately integrated the results in the patient's EHR. Results In a 12-month period, 862 unique patients completed 1,320 PRO assessments. The mean age of this cohort was 60.1 ± 16.3 years and 66% were male. The average time for PRO assessment was 6.7 minutes and the completion rate among eligible patients was 58%, with 91% of started assessments completed in full. Conclusions These preliminary data support the feasibility of serial PRO assessment with real-time integration into the EHR in a large outpatient population of patients with HF. We identified critical steps that should enhance adoption of this approach by clinicians and render PRO results meaningful and actionable in routine clinical care. [ABSTRACT FROM AUTHOR]

Despite advances in the medical and surgical management of cardiovascular disease, greater than 350,000 patients experience out-of-hospital cardiac arrest in the United States annually, with only a 12% neurologically favorable survival rate. Of these patients, 23% have an initial shockable rhythm of ventricular fibrillation/pulseless ventricular tachycardia (VF/VT), a marker of high probability of acute coronary ischemia (80%) as the precipitating factor. However, few patients (22%) will experience return of spontaneous circulation and sufficient hemodynamic stability to undergo cardiac catheterization and revascularization. Previous case series and observational studies have demonstrated the successful application of intra-arrest extracorporeal life support, including to out-of-hospital cardiac arrest victims, with a neurologically favorable survival rate of up to 53%. For patients with refractory cardiac arrest, strategies are needed to bridge them from out-of-hospital cardiac arrest to the catheterization laboratory and revascularization. To address this gap, we expanded our ICU and perioperative extracorporeal membrane oxygenation (ECMO) program to the emergency department (ED) to reach this cohort of patients to improve survival. In this report, we illustrate our process and initial experience of developing a multidisciplinary team for rapid deployment of ED ECMO as a template for institutions interested in building their own ED ECMO programs. [ABSTRACT FROM AUTHOR]

Background: Clinical studies have suggested the prognostic value of galectin-3, a marker of fibrosis, in chronic heart failure. However, the specific role of galectin-3, compared with established biomarkers, remains uncertain.Methods and Results: The Penn Heart Failure Study was an ambulatory heart failure cohort that included 1385 participants with reduced (1141), preserved (106), and recovered (138) left ventricular ejection fraction (LVEF). Cox regression models determined the association between galectin-3 and risk of all-cause mortality, cardiac transplantation, or placement of a ventricular assist device. Receiver operating characteristic curves compared the prognostic accuracy of galectin-3, high-sensitivity soluble Toll-like receptor 2 (ST2), troponin I, and B-type natriuretic peptide (BNP) at 1 and 5 years. Higher galectin-3 levels were associated with an increased risk of adverse events (adjusted hazard ratio of 1.96 for each doubling in galectin-3; P < .001). This association was most pronounced among participants with preserved LVEF (adjusted hazard ratio 3.30; P < .001). At 5 years, galectin-3 was the most accurate discriminator of risk among participants with preserved LVEF (area under the curve 0.782; P = .81 vs high-sensitivity ST2; P = .029 vs troponin I; P = .35 vs BNP). BNP was most accurate among participants with reduced and recovered LVEF (areas under the curves 0.716 and 0.728, respectively).Conclusions: Galectin-3 could have prognostic value for long-term events among patients with heart failure and preserved ejection fraction. [ABSTRACT FROM AUTHOR]

Advancements in the treatment of heart failure (HF) with systolic dysfunction have given rise to a new population of patients with improved ejection fraction (EF). The management of this distinct population is not well described due to a lack of consensus on the definition of myocardial recovery, a scarcity of data on the natural history of these patients, and the absence of focused clinical trials. Moreover, an improvement in EF may have different prognostic and management implications depending on the underlying etiology of cardiomyopathy. This can be challenging for the clinician who is approached by a patient inquiring about a reduction of medical therapy after apparent EF recovery. This review explores management strategies for HF patients with recovered EF in a disease-specific format. [ABSTRACT FROM AUTHOR]

Chronic oral anticoagulation frequently requires interruption for various reasons and durations. Whether or not to bridge with heparin or other anticoagulants is a common clinical dilemma. The evidence to inform decision making is limited, making current guidelines equivocal and imprecise. Moreover, indications for anticoagulation interruption may be unclear. New observational studies and a recent large randomized trial have noted significant perioperative or periprocedural bleeding rates without reduction in thromboembolism when bridging is employed. Such bleeding may also increase morbidity and mortality. In light of these findings, physician preferences for routine bridging anticoagulation during chronic anticoagulation interruptions may be too aggressive. More randomized trials, such as PERIOP2 (A Double Blind Randomized Control Trial of Post-Operative Low Molecular Weight Heparin Bridging Therapy Versus Placebo Bridging Therapy for Patients Who Are at High Risk for Arterial Thromboembolism), will help guide periprocedural management of anticoagulation for indications such as venous thromboembolism and mechanical heart valves. In the meantime, physicians should carefully consider both the need for oral anticoagulation interruption and the practice of routine bridging when anticoagulation interruption is indicated. [ABSTRACT FROM AUTHOR]

The presentation, natural history, clinical outcomes, and response to therapy in patients with heart failure differ in some ways across populations. Women, older adults, and non-Caucasian racial or ethnic groups compose a substantial proportion of the overall heart failure population, but they have typically been underrepresented in clinical trials. As a result, uncertainty exists about the efficacy of some guideline-directed medical therapies and devices in specific populations, which may result in the under- or overtreatment of these patients. Even when guideline-based treatments are prescribed, socioeconomic, physical, or psychologic factors may affect non-Caucasian and older adult patient groups to a different extent and affect the application, effectiveness, and tolerability of these therapies. Individualized therapy based on tailored biology (genetics, proteomics, metabolomics), socioeconomic and cultural considerations, and individual goals and preferences may be the optimal approach for managing diverse patients. This comprehensive approach to personalized medicine is evolving, but in the interim, the scientific community should continue efforts focused on intensifying research in special populations, prescribing guideline-directed medical therapy unless contraindicated, and implementing evidence-based strategies including patient and family education and multidisciplinary team care in the management of patients. [ABSTRACT FROM AUTHOR]

We propose that stage D advanced heart failure be defined as the presence of progressive and/or persistent severe signs and symptoms of heart failure despite optimized medical, surgical, and device therapy. Importantly, the progressive decline should be primarily driven by the heart failure syndrome. Formally defining advanced heart failure and specifying when medical and device therapies have failed is challenging, but signs and symptoms, hemodynamics, exercise testing, biomarkers, and risk prediction models are useful in this process. Identification of patients in stage D is a clinically important task because treatments are inherently limited, morbidity is typically progressive, and survival is often short. Age, frailty, and psychosocial issues affect both outcomes and selection of therapy for stage D patients. Heart transplant and mechanical circulatory support devices are potential treatment options in select patients. In addition to considering indications, contraindications, clinical status, and comorbidities, treatment selection for stage D patients involves incorporating the patient's wishes for survival versus quality of life, and palliative and hospice care should be integrated into care plans. More research is needed to determine optimal strategies for patient selection and medical decision making, with the ultimate goal of improving clinical and patient centered outcomes in patients with stage D heart failure. [ABSTRACT FROM AUTHOR]

Heart failure with preserved ejection fraction (HFpEF) is a common cardiovascular condition with significant morbidity and mortality. It is characterized by its comorbidity burden, mechanistic heterogeneity, and therapeutic paucity. Historically, therapeutic clinical trials have failed to provide therapies that improved clinical outcomes. However, recent large-scale randomized trials have provided evidence for relevant and effective treatment options for HFpEF patients, which now include the guideline-supported drug classes, angiotensin-receptor/neprilysin inhibitors (ARNi), mineralocorticoid antagonists (MRA), and sodium glucose cotransporter type 2 inhibitors (SGLT2i). Importantly, these drugs also appear to have important kidney benefits and may represent the impact of a cardiorenal approach to HFpEF. While the reduction in heart failure hospitalizations is consistent across studies and drug classes, their impact on cardiovascular and all-cause mortality remains unclear, raising important questions regarding the fundamental mechanisms of this complex condition. Moreover, improving quality of life in these patients continues to require a multidisciplinary approach that incorporates lifestyle-directed interventions and avoidance of polypharmacy. [ABSTRACT FROM AUTHOR]

Background Identification of heart failure (HF) patients at risk for hospitalization may improve care and reduce costs. We evaluated 9 biomarkers as predictors of cardiac hospitalization in chronic HF. Methods and Results In a multicenter cohort of 1,512 chronic HF outpatients, we assessed the association between 9 biomarkers and cardiac hospitalization with the use of a recurrent events approach. Over a median follow-up of 4 years, 843 participants experienced ≥1 hospitalizations (total 2,178 hospitalizations). B-type natriuretic peptide (BNP) and troponin I (TnI) exhibited the strongest associations with risk of hospitalization (hazard ratio [HR] 3.8 [95% confidence interval (CI) 2.9-4.9] and HR 3.3 [95% CI 2.8-3.9]; 3rd vs 1st tertiles). Soluble Fms-like tyrosine kinase receptor 1 (sFlt-1) exhibited the next strongest association (HR 2.8 [95% CI 2.4-3.4]), followed by soluble Toll-like receptor 2 (HR 2.3 [95% CI 2.0-2.8]) and creatinine (HR 1.9 [95% CI 1.6-2.4]). Within ischemic/nonischemic subgroups, BNP and TnI remained most strongly associated. Except for creatinine, HRs for all biomarkers studied were smaller within the ischemic subgroup, suggesting greater importance of cardiorenal interactions in decompensation of ischemic HF. Conclusion Although BNP and TnI exhibited the strongest associations with hospitalization, etiology-dependent associations for the remaining biomarkers suggest etiology-specific mechanisms for HF exacerbation. sFlt-1 exhibited a strong association with cardiac hospitalization, highlighting its potential role as a biomarker of HF morbidity. [ABSTRACT FROM AUTHOR]

Although significant cardiac structural and functional improvement is a prerequisite for an LVAD-supported patient to be considered for device weaning, multiple factors including patient willingness, physician expertise, and center experience, weigh in on this complex decision. Existing predictive models defining cardiac recovery as device removal might underestimate the reverse remodeling rates. To develop a predictive tool to identify patients prone to improve cardiac structure and function, independent of the complex decision to deactivate a durable, surgically deployed device. Advanced chronic HF patients (N=703) requiring continuous-flow LVADs were evaluated. After excluding patients with acute HF etiologies and/or inadequate post-LVAD follow-up (<3 months), 3 US programs contributed 390 patients (derivation cohort), while 5 US programs formed the validation cohort (n=245). We defined responders as patients with an LVEF ≥40% and LVEDD ≤6.0 cm within the first year of LVAD support. Multivariable logistic regression on the derivation set yielded a predictive model, which was externally tested; a predictive score was developed. Overall, 18.5% of the patients were responders. Compared to the validation, patients in the derivation cohort were more likely white (83 vs 69%; p<0.001), with ischemic HF (42 vs 33%; p=0.04), and longer HF duration (88 vs 66 months; p<0.001). Multivariable predictors of responders and the derived scoring system are shown in the Figure (c-statistic 0.74 [95% CI: 0.66-0.83] and 0.71 [95% CI: 0.59-0.77] in the derivation and validation set). Focused on patients experiencing significant reverse remodeling post-LVAD support we developed a predictive score achieving good discriminative performance in distinct, heterogeneous, contemporary cohorts. This tool can be useful in selecting patients to implement diagnostic and therapeutic protocols to promote reverse remodeling and myocardial recovery. [ABSTRACT FROM AUTHOR]

Abstract: Acute decompensated heart failure (ADHF) is a complex clinical event associated with excess morbidity and mortality. Managing ADHF patients is challenging because of the lack of effective treatments that both reduce symptoms and improve clinical outcomes. Existing guideline recommendations are largely based on expert opinion, but several recently published trials have yielded important data to inform both current clinical practice and future research directions. New insight has been gained regarding volume management, including dosing strategies for intravenous loop diuretics and the role of ultrafiltration in patients with heart failure and renal dysfunction. Although the largest ADHF trial to date (ASCEND-HF, using nesiritide) was neutral, promising results with other investigational agents have been reported. If these findings are confirmed in phase III trials, novel compounds, such as relaxin, omecamtiv mecarbil, and ularitide, among others, may become therapeutic options. Translation of research findings into quality clinical care can not be overemphasized. Although many gaps in knowledge exist, ongoing studies will address issues around delivery of evidence-based care to achieve the goal of improving the health status and clinical outcomes of patients with ADHF. [Copyright &y& Elsevier]

Abstract: The optimal management for ischemic cardiomyopathy has been a clinical conundrum for years. Until the publication of the Surgical Treatment of Ischemic Cardiac Heart Failure (STICH) trial, recommendations have been primarily based upon expert opinion, retrospective literature, and clinical anecdotes. However, medical and device management have matured significantly in an era where surgical morbidity and mortality remain significant for coronary bypass grafting in the setting of severe left ventricular dysfunction. For the first time in years, there now exists a landmark prospective randomized clinical trial that addresses the role of coronary bypass surgery as an initial strategy for ischemic cardiomyopathy. Although many interpretations of STICH exist, the neutral results of STICH should reassure clinicians that a strategy of initiating and optimizing medical therapy and deferring surgical revascularization for ischemic cardiomyopathy in “STICH-like patients” is effective, safe, and tested. [Copyright &y& Elsevier]

Pulmonary hypertension associated with left heart disease is the most common form of pulmonary hypertension encountered in clinical practice today. Although frequently a target of therapy, its pathophysiology remains poorly understood and its treatment remains undefined. Pulmonary hypertension in the context of left heart disease is a marker of worse prognosis and disease severity, but whether its primary treatment is beneficial or harmful is unknown. An important step to the future study of this important clinical problem will be to standardize definitions across disciplines to facilitate an evidence base that is interpretable and applicable to clinical practice. In this current statement, we provide an extensive review and interpretation of the current available literature to guide current practice and future investigation. At the request of the Pulmonary Hypertension (PH) Council of the International Society for Heart and Lung Transplantation (ISHLT), a writing group was assembled and tasked to put forth this document as described above. The review process was facilitated through the peer review process of the Journal of Heart and Lung Transplantation and ultimately endorsed by the leadership of the ISHLT PH Council. [Copyright &y& Elsevier]

Abstract: Aldosterone antagonists (or mineralocorticoid receptor antagonists [MRAs]) are guideline-recommended therapy for patients with moderate to severe heart failure (HF) symptoms and reduced left ventricular ejection fraction (LVEF), and in postmyocardial infarction patients with HF. The Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF) trial evaluated the MRA eplerenone in patients with mild HF symptoms. Eplerenone reduced the risk of the primary endpoint of cardiovascular death or HF hospitalization (hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.54–0.74, P < .001) and all-cause mortality (adjusted HR 0.76, 95% CI 0.62–0.93, P < .008) after a median of 21 months. Based on EMPHASIS-HF, an MRA is recommended for patients with New York Heart Association (NYHA) Class II–IV symptoms and reduced LVEF (<35%) on standard therapy (Strength of Evidence A). Patients with NYHA Class II symptoms should have another high-risk feature to be consistent with the EMPHASIS-HF population (age >55 years, QRS duration >130 msec [if LVEF between 31% and 35%], HF hospitalization within 6 months or elevated B-type natriuretic peptide level). Renal function and serum potassium should be closely monitored. Dose selection should consider renal function, baseline potassium, and concomitant drug interactions. The efficacy of eplerenone in patients with mild HF symptoms translates into a unique opportunity to reduce morbidity and mortality earlier in the course of the disease. [Copyright &y& Elsevier]

Abstract: Cardiac resynchronization therapy (CRT) improves survival, symptoms, quality of life, exercise capacity, and cardiac structure and function in patients with New York Heart Association (NYHA) functional class II or ambulatory class IV heart failure (HF) with wide QRS complex. The totality of evidence supports the use of CRT in patients with less severe HF symptoms. CRT is recommended for patients in sinus rhythm with a widened QRS interval (≥150 ms) not due to right bundle branch block (RBBB) who have severe left ventricular (LV) systolic dysfunction and persistent NYHA functional class II-III symptoms despite optimal medical therapy (strength of evidence A). CRT may be considered for several other patient groups for whom evidence of benefit is clinically significant but less substantial, including patients with a QRS interval of ≥120 to <150 ms and severe LV systolic dysfunction who have persistent mild to severe HF despite optimal medical therapy (strength of evidence B), some patients with atrial fibrillation, and some with ambulatory class IV HF. Several evidence gaps remain that need to be addressed, including the ideal threshold for QRS duration, QRS morphology, lead placement, degree of myocardial scarring, and the modality for evaluating dyssynchrony. Recommendations will evolve over time as additional data emerge from completed and ongoing clinical trials. [Copyright &y& Elsevier]

Abstract: Background: Hypertension is an important risk factor for the development of heart failure with preserved ejection fraction. Although heart failure in hypertensive patients is usually ascribed to intrinsic myocardial abnormalities, noncardiac factors may contribute. Methods and Results: Using arterial tonometry and Doppler echocardiography, we assessed arterial stiffness and cardiac diastolic function in 53 individuals with ejection fraction >=0.50, including 23 with hypertension but no heart failure, 16 with hypertension and heart failure, and 14 healthy, normotensive controls. Relative to healthy controls and hypertensives, subjects with heart failure had higher systolic blood pressure, body mass index, creatinine, and left ventricular mass. Diastolic function, as estimated by myocardial relaxation velocity, was not different among the 3 groups. Peripheral arterial stiffness was similar across all groups, but key measures of central aortic stiffness (carotid-femoral pulse wave velocity, characteristic impedance, forward wave amplitude) steadily increased with progression from healthy to hypertensive to heart failure despite adjustment for body mass index, systolic blood pressure, and renal function and were positively correlated with both left ventricular mass and filling pressure. Conclusions: We conclude that patients with heart failure and preserved ejection fraction have increased central aortic stiffness relative to age-matched healthy and hypertensive subjects without heart failure. These changes exceed differences in diastolic function and suggest that abnormal ventricular-vascular coupling may contribute to the pathophysiology of heart failure with preserved ejection fraction. [Copyright &y& Elsevier]

Abstract: Objective: In chronic heart failure (HF), diuretic doses increase as the disease progresses, often after hospitalization for instability, and have been associated with worsening renal function and increased mortality. Methods and Results: A prospective observational analysis of 183 patients in an advanced HF clinic stratified at baseline by diuretic dose (low dose ≤ 80 mg, high dose > 80 mg furosemide equivalent) was performed. All patients were followed for 1 year, and the primary outcome was a combined HF event of admission for HF, cardiac transplant, mechanical cardiac support, or death. Compared with patients taking low-dose diuretics (n = 113), patients taking high-dose diuretics (n = 70) had more markers of increased cardiovascular risk and were more likely to have a history of recent instability (33% vs 4.4% in low dose, P < .001). High doses of diuretics were a strong univariate predictor of subsequent HF events (hazard ratio 3.83, 95% confidence interval 1.82–8.54); however, after adjustment for clinical stability, diuretic dose no longer remained significant (hazard ratio 1.53, 95% confidence interval 0.58–4.03). Conclusion: High-dose diuretics may be more of a marker than a cause of instability. A history of HF stability during the past 6 months is associated with an 80% lower risk of an HF event during the next year, independently of baseline diuretic dose. [Copyright &y& Elsevier]

Objectives: The purpose of this study was to describe the clinical, angiographic, and histological features of concomitant in-stent restenosis (ISR) and cardiac allograft vasculopathy (CAV) progression. Background: Cardiac allograft vasculopathy is a major challenge to long-term success of heart transplantation. Coronary stenting for CAV is hampered by ISR. Methods: Quantitative coronary angiography compared late lumen loss (LL) at stented and reference, non-stented segments during 1-year follow-up in post-heart transplant and control atherosclerosis patients. Stented and non-stented arteries with CAV were also obtained post-mortem for immunohistochemical analysis. Results: In 37 stented lesions (25 patients), 1-year binary restenosis occurred in 37.8%. Patients with ISR had higher long-term cardiac death/myocardial infarction rates than patients without ISR (53.8% vs. 9.1%, p = 0.03). In the same 25 patients, 34 CAV lesions with non-significant obstructions were identified as reference controls. After 1 year, patients who developed ISR also had more control lesion LL (0.78 ± 0.38 mm vs. 0.39 ± 0.27 mm, p < 0.006) compared to patients without ISR. In the post-transplant patients, in-stent LL was closely coupled to control segment LL (R2 = 0.63, p < 0.05). Conversely, in native atherosclerosis patients, ISR and remote disease progression were not correlated. Histological staining of stented and control arteries from CAV patients revealed similar pathologies common to ISR and non-intervened CAV segments. Conclusions: Progression of CAV at non-intervened segments and ISR correlate strongly and share common histopathology. Optimized treatment for patients with aggressive CAV needs to address the widespread nature of this disease, even when it presents as an initially focal lesion. [Copyright &y& Elsevier]

Abstract: Background: Therapies for heart failure (HF) with a low ejection fraction (EF) have delayed disease progression and prolonged survival, but the implications of these therapies on the end stages of HF have not been examined. Methods and Results: Patients seen by the Brigham and Women''s cardiomyopathy service with an EF ≤35%, at least 1 outpatient visit or at least 30 days of follow-up who died between January 1, 2000, and October 20, 2003, were evaluated retrospectively. Of the 160 patients who died since 2000, 80 (50%) were outpatients. In the 6 months before death, 93% of patients had New York Heart Association (NYHA) class III or IV symptoms. The NYHA class, clinical characteristics, medications, and comorbidities differed little between inpatient and outpatient deaths. Renal insufficiency and hyponatremia were worse in the months preceding death than at the time of death (creatinine: 3.2 versus 2.3 mg/dL, P < .0001; sodium: 128 versus 135 mmol/L, P < .0001, respectively). Death was considered sudden in only 21% of patients. Conclusion: Deaths in the current era of HF management occur in patients with long-standing HF characterized by biventricular dysfunction and advanced symptoms. Most deaths are heralded by hyponatremia, acute on chronic renal insufficiency, and frequent hospitalizations. [Copyright &y& Elsevier]

We sought to explore the relation between Chlamydia pneumoniae, cytomegalovirus (CMV), and cardiac transplant-associated arteriosclerosis. Serologic evidence of past Chlamydia pneumoniae infection was investigated in 3 patient groups at the time of cardiac catheterization: cardiac transplant recipients (n=49), patients having coronary artery bypass grafting (CABG) (n=39), and a control group free of angiographic coronary artery disease (n=21). High Chlamydia pneumoniae immunoglobulin G titers (> or =1:160) were more frequently observed in cardiac transplant recipients (odds ratio[OR] 13.7; 95% confidence intervals [CI] 1.6 to 117.4, p <0.05) and CABG patients (OR 21.7; 95% CI 1.6 to 287.0, p <0.05) than in controls. However, high Chlamydia pneumoniae titers did not distinguish between cardiac transplant recipients with or without angiographic transplant-associated arteriosclerosis or CABG patients with or without bypass vein graft disease. Furthermore, there was no significant relation between elevated Chlamydia pneumoniae titers and the presence or progression of transplant-associated arteriosclerosis in the subgroup of patients who were also CMV positive. Yet, analysis of the same angiograms demonstrated an association between CMV infection and the recent progression of transplant-associated arteriosclerosis. Thus, patients with cardiac transplantation have evidence of past Chlamydia pneumoniae and CMV infection but Chlamydia pneumoniae does not appear to have an independent role or synergistic relation to CMV in the development of transplant-associated arteriosclerosis. [ABSTRACT FROM AUTHOR]

Recipient-to-donor atrioatrial conduction across a suture line has been rarely reported after orthotopic heart transplantation. The relation of such conduction to symptomatic arrhythmias and its prevalence are not known. Recipient-to-donor atrioatrial conduction was demonstrated in a 28-year-old woman with paroxysmal supraventricular tachycardia 7 years after orthotopic heart transplantation. Atrial tachycardia in the recipient atria conducted 2:1 to the donor atria and was eliminated by radiofrequency catheter ablation of a left-sided atrioatrial electrical connection. The electrocardiogram at rest and during exercise, recorded before ablation of the recipient-to-donor connection, showed frequent atrial premature complexes, with variable coupling to the preceding sinus beats, and a change in P-wave morphology during exercise, which reverted to normal during the recovery period. These findings were eliminated by ablation of the recipient-to-donor connection. To determine the prevalence of recipient-to-donor atrioatrial conduction late after transplantation, we evaluated the exercise electrocardiograms of 50 subjects > 5 years after heart transplantation for these features of recipient-to-donor conduction. At least 1 feature was present in 5 subjects, and both were present in 1 subject. Electrical conduction can occur across surgical suture lines in the atria. Recipient-to-donor atrioatrial conduction may occur in < or = 10% of patients late after heart transplantation. It is a potential cause of arrhythmias that can be effectively treated with radiofrequency catheter ablation. [ABSTRACT FROM AUTHOR]

Outcomes of patients with advanced heart failure (HF) due to restrictive cardiomyopathy (RCM) remain unfavorable in spite of advances in HF therapies. Left ventricular assist devices (LVADs) are a standard therapeutic option for patients with advanced HF, however there is limited data to support LVAD implantation in these patients. The purpose of this study was to examine outcomes in patients with end-stage RCM following LVAD implantation when compared with those with dilated cardiomyopathies (DCM). The International Registry for Mechanically Assisted Circulatory Support (IMACS) registry was queried for all patients with RCM (n = 179) and DCM (n = 15,335) who underwent durable LVAD implantation between January 2013 and September 2017. Patients with RCM were grouped into amyloidosis, sarcoidosis, radiotherapy, idiopathic and other forms of RCM. Baseline patient characteristics, survival, and adverse events were compared among the groups. Patients with RCM had a mean age of 56 years and were predominately male (78.9%). Echocardiograms of patients with RCM had significantly smaller left ventricular end-diastolic diameter (LVEDD) compared to DCM (6.3 cm vs 6.8 cm p <0.001) and similar distribution in ejection fraction (50.9% with EF < 20% vs 57.4% p = 0.76, respectively). There was no significant difference in mortality (25.1% vs 21.5%, p = 0.234) or time to death (9.3 ± 11.9 months vs 10.2 ± 11.2 months, p = 0.567) between the groups. There were also similar rates of stroke (15.6% vs 16.2%, p = 0.829), bleeding (37.4% vs 35.9%, p = 0.678), driveline infection (12.3% vs 15.2%, p 0.282), and pump thrombosis (0 % vs 0.8%). When comparing subgroups of RCM, patients with amyloid cardiomyopathy were significantly older with a mean age of 62 (55-71) and had smaller LVEDD 4.7 cm (3.9-5.3) but there were no statistically significant differences in mortality or adverse events between the RCM subgroups In this analysis of an international registry, we demonstrated that patients with RCM have similar outcomes compared with patients with DCM following LVAD implantation. This observation invites future prospective investigations on validating our findings and on identifying challenges in regards to LVAD implantation in patients with advanced HF due to RCM. [ABSTRACT FROM AUTHOR]

Central sleep apnea (CSA) has been associated with a poor prognosis in patients with heart failure (HF). CSA in HF is associated with fatigue, daytime sleepiness, higher rates of HF-related readmission within 6 months and. Treatment of CSA using transvenous phrenic nerve stimulation (TPNS) with the remedē system has been shown to be safe and effective through 36 months of therapy in those with moderate-to-severe CSA with underlying HF, demonstrating improvement in sleep metrics, daytime sleepiness and quality of life regardless of HF. The aim of this analysis was to evaluate clinically relevant echocardiographic changes seen in patients within all HF subtypes. We hypothesized no adverse change on echocardiography would occur with CSA therapy. Patients with CSA and HF who participated in the remedē system Pivotal trial were implanted with the remedē system with therapy activation 1-month post-implant in the treatment group and 6-months post-implant in the control group. The groups were then pooled for analysis based on months of active therapy. Echocardiography was performed at 6, 12, and 18 months with attention to the right ventricular end-diastolic diameter (RVEDD), tricuspid annular planar systolic excursion (TAPSE) and right ventricular (RV) ejection time. Subjects with permanent atrial fibrillation were excluded. Based on pooled data, there was no clinically meaningful change from baseline in RVEDD, TAPSE and RV ejection time in any of the EF subgroups (HFrEF [EF<40%], HFmrEF [EF40-50%] and HFpEF [EF ≥ 50%]) at 6, 12, and 18 months (see Table 1). This is the first analysis of echocardiographic changes among HF patients with CSA across the EF spectrum receiving TPNS. In concert with prior data, no adverse structural consequences were observed in these echocardiographic parameters of TPNS. These data reveal that transvenous stimulation of the phrenic nerve in patients with HF and CSA may be a therapeutic option for patients regardless of EF. [ABSTRACT FROM AUTHOR]

Central sleep apnea is a frequent finding in heart failure (HF) and is being increasingly reported in heart failure patients with preserved ejection fraction (HFpEF). Mechanisms of CSA occurrence in those with HFpEF may be similar to CSA in HF with reduced ejection fraction (HFrEF). While treatment of CSA in HFrEF has been reported to be safe and associated with improved sleep metrics, long-term follow-up in patients with moderately reduced ejection fraction (HFmrEF - EF 40-50%) or HFpEF (EF > 50%) and CSA is not well understood. The aim of this analysis was to evaluate changes in LVEF and natriuretic peptides in patients with HFmrEF or HFpEF and CSA following transvenous phrenic nerve stimulation (TPNS). We hypothesized no meaningful reduction in LVEF or increase in natriuretic peptides would be observed. Patients who participated in the remedē system Pivotal trial had TPNS activated 1-month post-implant in the treatment group and 6-months post-implant in the control group. The groups were then pooled for post hoc analysis based on months of active therapy. Echocardiography was performed at 6, 12, and 18 months with attention to EF%, particularly in those without permanent atrial fibrillation, as well as measurement of BNP or NT-pro-BNP at those time points. : The HFmrEF group had a median EF of 49.5% [interquartile range (IQR) - 47.0, 53.0] (n=10) at 18 months with a paired change from baseline of 5.0% [2.0, 8.0] (p = 0.031). The HFpEF group had an EF of 56.0% [54.0, 58.0] (n = 10) at 18 months with a paired change from baseline of 1.5% [0.0, 4.0] (p = 0.086). Based on pooled data there was no clinically meaningful change in BNP or NT-pro-BNP over the course of 18 months of active therapy (Table 1). This analysis shows no clinically meaningful change in EF based on echocardiographic changes and no clinically meaningful changes in natriuretic peptides following TPNS activation in patients with HFmrEF or HFpEF. Future studies in this patient population should be considered. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic disrupted the way care is delivered to patients with chronic conditions such as heart failure (HF). Many outpatient encounters are now conducted virtually via telehealth. Whether virtual visit for HF results in similar type of interventions as when the patient is seen in person is not known. Starting on March 15, 2020, all non-time sensitive outpatient in-person appointments at our institution were cancelled and transitioned to virtual appointments where possible. We included all patients seen in a tertiary care HF clinic from February 18 to March 13 (pre-Covid) and from March 16 to May 15 (post-COVID). We examined the volume of in-person and virtual visits and compared medication titration rates pre- and post-COVID. The study cohort included 745 patients, mean age 60.7+/-15.3 years, 65.2% male, 80.9% Caucasian, 7.7% Hispanic/Latino. Of these, 227 patients were seen pre-COVID and 518 post-COVID. All appointments were in-person pre-COVID. After the change, only 18% of appointments were in-person while 82% were virtual. Outpatient volume decreased after March 15, but gradually increased, eventually to volumes that exceeded pre-COVID (Figure). Detailed results on medication titration are shown in Table. Diuretic titration took place in 33/227 (14.5%) of patients pre-COVID and 83/518 (16.0%) post-COVID (p=NS). Among 567 patients with HF with reduced ejection fraction (HFrEF), titration of guideline-directed medical therapy (GDMT) took place in 86/172 (50.0%) of patients pre-COVID and 159/395 (40.2%) post-COVID (p=0.03). Among the 395 HFrEF patients seen post-COVID, GDMT was titrated in 33/68 (48.5%) patients seen in person and 126/327 (38.5%) seen virtually - p=0.13. Barriers to medication titration in virtual visits were lack of blood pressure readings and lack of recent laboratory results. Telehealth has become an essential method of outpatient care delivery for chronic HF. Once implemented, it offered efficiencies including improved access to the HF clinic thanks to higher throughput capacity compared to physical clinic space. However, we identified that GDMT titration took place less frequently than during in-person visits. Since it is anticipated that telehealth use will continue into the future, approaches to maximize GDMT in the absence of traditional direct physical contact with HF patients are needed. [ABSTRACT FROM AUTHOR]

Examines the use of the thrombolysis in myocardial infarction frame count for the quantitative assessment of transplant-associated arteriosclerosis (TAA). Reliance on surveillance coronary angiography of clinical practice for the assessment of TAA; Quantitative approach to assessing TAA; Absence of severe structural narrowings in epicardial arteries.