Patient Focus: Moving Beyond Step Count: An Explanation of Real-World Walking Behaviors Are Associated With Early-Stage Heart Failure: A Project Baseline Health Study.

In this issue of the Journal of Cardiac Failure, Dr. Sooyoon Shin and colleagues look at whether information from wearable devices, or activity trackers, could improve how a medical team monitors activity limitations for people who are at risk of developing heart failure symptoms.

Integration of Patient Reported Quality-of-life Data into Risk Assessment in Heart Failure.

BACKGROUND: Optimal management of outpatients with heart failure (HF) requires serially updating the estimates of their risk for adverse clinical outcomes to guide treatment. Patient-reported outcomes (PROs) are becoming increasingly used in clinical care. The purpose of this study was to determine whether the inclusion of PROs can improve the risk prediction for HF hospitalization and death in ambulatory patients with HF. METHODS AND RESULTS: We included consecutive patients with HF with reduced ejection fraction (HFrEF) and HF with preserved EF (HFpEF) seen in a HF clinic between 2015 and 2019 who completed PROs as part of routine care. Cox regression with a least absolute shrinkage and selection operator regularization and gradient boosting machine analyses were used to estimate risk for a combined outcome of HF hospitalization, heart transplant, left ventricular assist device implantation, or death. The performance of the prediction models was evaluated with the time-dependent concordance index (Cτ). Among 1165 patients with HFrEF (mean age 59.1 ± 16.1, 68% male), the median follow-up was 487 days. Among 456 patients with HFpEF (mean age 64.2 ± 16.0 years, 55% male) the median follow-up was 494 days. Gradient boosting regression that included PROs had the best prediction performance - Cτ 0.73 for patients with HFrEF and 0.74 in patients with HFpEF, and showed very good stratification of risk by time to event analysis by quintile of risk. The Kansas City Cardiomyopathy Questionnaire overall summary score, visual analogue scale and Patient Reported Outcomes Measurement Information System dimensions of satisfaction with social roles and physical function had high variable importance measure in the models. CONCLUSIONS: PROs improve risk prediction in both HFrEF and HFpEF, independent of traditional clinical factors. Routine assessment of PROs and leveraging the comprehensive data in the electronic health record in routine clinical care could help more accurately assess risk and support the intensification of treatment in patients with HF.

Bridge-to-transplant temporary mechanical circulatory support and risk of allosensitization.

INTRODUCTION: Since the 2018 change in the US adult heart allocation policy, more patients are bridged-to-transplant on temporary mechanical circulatory support (tMCS). Previous studies indicate that durable left ventricular assist devices (LVAD) may lead to allosensitization. The goal of this study was to assess whether tMCS implantation is associated with changes in sensitization. METHODS: We included patients evaluated for heart transplants between 2015 and 2022 who had alloantibody measured before and after MCS implantation. Allosensitization was defined as development of new alloantibodies after tMCS implant. RESULTS: A total of 41 patients received tMCS before transplant. Nine (22.0%) patients developed alloantibodies following tMCS implantation: 3 (12.0%) in the intra-aortic balloon pump group (n = 25), 2 (28.6%) in the microaxial percutaneous LVAD group (n = 7), and 4 (44.4%) in the veno-arterial extra-corporeal membrane oxygenation group (n = 9)-p = .039. Sensitized patients were younger (44.7 ± 11.6 years vs. 54.3 ± 12.5 years, p = .044), were more likely to be sensitized at baseline - 3 of 9 (33.3%) compared to 2 out of 32 (6.3%) (p = .028) and received more transfusions with red blood cells (6 (66.6%) vs. 8 (25%), p = .02) and platelets (6 (66.6%) vs. 5 (15.6%), p = .002). There was no significant difference in tMCS median duration of support (4 [3,15] days vs. 8.5 [5,14.5] days, p = .57). Importantly, out of the 11 patients who received a durable LVAD after tMCS, 5 (45.5%) became sensitized, compared to 4 out of 30 patients (13.3%) who only had tMCS-p = .028. CONCLUSIONS: Our findings suggest that patients bridged-to-transplant with tMCS, without significant blood product transfusions and a subsequent durable LVAD implant, have a low risk of allosensitization. Further studies are needed to confirm our findings and determine whether risk of sensitization varies by type of tMCS and duration of support.

The Cardiac Amyloidosis Registry Study (CARS): Rationale, Design and Methodology.

BACKGROUND: CARS (Cardiac Amyloidosis Registry Study) is a multicenter registry established in 2019 that includes patients with transthyretin (ATTR, wild-type and variant) and light chain (AL) cardiac amyloidosis (CA) evaluated at major amyloidosis centers between 1997 and 2025. CARS aims to describe the natural history of CA with attention to clinical and diagnostic variables at the time of diagnosis, real-world treatment patterns, and associated outcomes of patients in a diverse cohort that is more representative of the at-risk population than that described in CA clinical trials. METHODS AND RESULTS: This article describes the design and methodology of CARS, including procedures for data collection and preliminary results. As of February 2023, 20 centers in the United States enrolled 1415 patients, including 1155 (82%) with ATTR and 260 (18%) with AL CA. Among those with ATTR, wild-type is the most common ATTR (71%), and most of the 305 patients with variant ATTR have the p.V142I mutation (68%). A quarter of the total population identifies as Black. More individuals with AL are female (39%) compared to those with ATTR (13%). CONCLUSIONS: CARS will answer crucial clinical questions about CA natural history and permit comparison of different therapeutics not possible through current clinical trials. Future international collaboration will further strengthen the validity of observations of this increasingly recognized condition.

Association of Body Mass Index and Age With Morbidity and Mortality in Patients Hospitalized With COVID-19: Results From the American Heart Association COVID-19 Cardiovascular Disease Registry.

BACKGROUND: Obesity may contribute to adverse outcomes in coronavirus disease 2019 (COVID-19). However, studies of large, broadly generalizable patient populations are lacking, and the effect of body mass index (BMI) on COVID-19 outcomes- particularly in younger adults-remains uncertain. METHODS: We analyzed data from patients hospitalized with COVID-19 at 88 US hospitals enrolled in the American Heart Association's COVID-19 Cardiovascular Disease Registry with data collection through July 22, 2020. BMI was stratified by World Health Organization obesity class, with normal weight prespecified as the reference group. RESULTS: Obesity, and, in particular, class III obesity, was overrepresented in the registry in comparison with the US population, with the largest differences among adults ≤50 years. Among 7606 patients, in-hospital death or mechanical ventilation occurred in 2109 (27.7%), in-hospital death in 1302 (17.1%), and mechanical ventilation in 1602 (21.1%). After multivariable adjustment, classes I to III obesity were associated with higher risks of in-hospital death or mechanical ventilation (odds ratio, 1.28 [95% CI, 1.09-1.51], 1.57 [1.29-1.91], 1.80 [1.47-2.20], respectively), and class III obesity was associated with a higher risk of in-hospital death (hazard ratio, 1.26 [95% CI, 1.00-1.58]). Overweight and class I to III obese individuals were at higher risk for mechanical ventilation (odds ratio, 1.28 [95% CI, 1.09-1.51], 1.54 [1.29-1.84], 1.88 [1.52-2.32], and 2.08 [1.68-2.58], respectively). Significant BMI by age interactions were seen for all primary end points (P-interaction<0.05 for each), such that the association of BMI with death or mechanical ventilation was strongest in adults ≤50 years, intermediate in adults 51 to 70 years, and weakest in adults >70 years. Severe obesity (BMI ≥40 kg/m2) was associated with an increased risk of in-hospital death only in those ≤50 years (hazard ratio, 1.36 [1.01-1.84]). In adjusted analyses, higher BMI was associated with dialysis initiation and with venous thromboembolism but not with major adverse cardiac events. CONCLUSIONS: Obese patients are more likely to be hospitalized with COVID-19, and are at higher risk of in-hospital death or mechanical ventilation, in particular, if young (age ≤50 years). Obese patients are also at higher risk for venous thromboembolism and dialysis. These observations support clear public health messaging and rigorous adherence to COVID-19 prevention strategies in all obese individuals regardless of age.

Biomarker-Based Assessment for Infectious Risk Before and After Heart Transplantation.

PURPOSE OF REVIEW: Survival outcomes for heart transplant recipients have improved in recent decades, but infection remains a significant cause of morbidity and mortality. In this review, we discuss several biological markers, or biomarkers, that may be used to monitor immunologic status in this patient population. RECENT FINDINGS: While modest, data on the utility of immune biomarkers in heart transplant recipients suggest correlation between low level of immune response and increased infection risk. More novel assays, such as the detection of circulating levels of pathogen cell-free DNA in plasma and the use of Torque teno virus load as a surrogate for net state of immunosuppression, have potential to be additional important biomarkers. Biomarker approaches to individualize immunosuppression therapy among heart transplant recipients is a promising area of medicine. However, additional studies are needed to inform the optimal protocol in which to incorporate these biomarkers into clinical practice.

Disparities in acute decompensated heart failure.

PURPOSE OF REVIEW: The aim of this review is to discuss racial and sex disparities in the management and outcomes of patients with acute decompensated heart failure (ADHF). RECENT FINDINGS: Race and sex have a significant impact on in-hospital admissions and overall outcomes in patients with decompensated heart failure and cardiogenic shock. Black patients not only have a higher incidence of heart failure than other racial groups, but also higher admissions for ADHF and worse overall survival, while women receive less interventions for cardiogenic shock complicating acute myocardial infarction. Moreover, White patients are more likely than Black patients to be cared for by a cardiologist than a noncardiologist in the ICU, which has been linked to overall improved survival. In addition, recent data outline inherent racial and sex bias in the evaluation process for advanced heart failure therapies indicating that Black race negatively impacts referral for transplant, women are judged more harshly on their appearance, and that Black women are perceived to have less social support than others. This implicit bias in the evaluation process may impact appropriate timing of referral for advanced heart failure therapies. SUMMARY: Though significant racial and sex disparities exist in the management and treatment of patients with decompensated heart failure, these disparities are minimized when therapies are properly utilized and patients are treated according to guidelines.

Angiotensin Receptor-Neprilysin Inhibitors and the Natriuretic Peptide Axis.

PURPOSE OF THE REVIEW: The purpose of this review is to describe the effects of angiotensin receptor neprilysin inhibitor (ARNI) therapy on the natriuretic peptide axis (NPA), with a particular focus on B-type natriuretic peptide (BNP), atrial natriuretic peptide (ANP), and C-type natriuretic peptide (CNP) to better understand the biology behind the improved outcomes in patients with heart failure with reduced ejection fraction (HFrEF). RECENT FINDINGS: BNP, ANP, and CNP are the three main natriuretic peptides (NP); they share a common structure and ultimately mediate their actions by activating cyclic guanosine monophosphate (cGMP). ARNI therapy results in a decrease of N-terminal pro-BNP (NT-proBNP) and increase of BNP levels respectively. It is been questioned whether these changes may result from unique laboratory assays characteristics rather than actual biological implications. It appears to be that the prognostic accuracy of BNP for cardiovascular outcomes remains independent and comparable to that of NT-proBNP while on ARNI therapy. ANP levels also increase with ARNI therapy, but no consistent change has been described for CNP levels. There is evidence that the changes in BNP and NT-proBNP correlate with improvement in echocardiographic parameters of volume and function. The dual effect of neprilysin inhibition and angiotensin receptor blockade has substantial implications on the natriuretic peptide axis (NPA). The changes seen in BNP and NT-proBNP specifically have shown to correlate with improvement in echocardiographic parameters. Further results exploring the biologic effects of ARNI therapy on other NPs are still pending and likely will provide further insights in the mechanisms behind the improvement in cardiac function and clinical outcomes.

Renal Medullary Carcinoma and Sickle Cell Trait: A Push for Early Diagnosis and Intervention Report of Two Cases.

Renal medullary carcinoma (RMC) is a rare but highly aggressive neoplasm that primarily affects young African Americans with sickle cell trait. Most patients present with macroscopic hematuria and have metastases at diagnosis. Chemotherapy, biologics directed against the more common renal cell carcinomas and radiation have all shown limited efficacy in treating patients with advanced RMC. We report two patients with RMC. Both had Stage IV disease. One underwent radical nephrectomy followed by radiation and biologic drug therapy but died five months later; the other underwent multiple cycles of chemotherapy plus anti-angiogenesis treatment but died 15 months after diagnosis. Review of the literature suggests that early diagnosis and surgical intervention while the tumor is confined to the kidney offer the best prospect for long term survival. Since newborn screening for sickle cell is now mandated in the US, the at-risk population for RMC could be identified and followed by yearly urine dipstick testing for microscopic hematuria. Those who test positive can be further evaluated to rule out RMC.

Social, Racial, and Cultural Considerations in Hypertension in Older Adults.

Black and Hispanic older adults in the United States have higher prevalence of hypertension, less adequate treatment, less consistent blood pressure control, and worse cardiovascular outcomes than their white counterparts. Genetic differences are insufficient to explain these disparities-various social, economic, and environmental factors notably contribute. Racial and ethnic differences in living circumstances, household income, access to appropriate care, food security, educational attainment, and tobacco use all negatively impact long-term hypertension outcomes in minoritized older adults. To remedy these inequities, the search for solutions must include a complete assessment of the social, racial, and cultural components of the problem.

A Case of Stress-Induced Cardiomyopathy After Ketamine Infusion.

We report the case of a 64-year-old female with a history of hypothyroidism and isolated parotid sarcoidosis who presented with acute-onset chest pain and dyspnea. Echocardiogram demonstrated transiently reduced ejection fraction with apical hypokinesis, without evidence of obstructive coronary lesions on angiography, compatible with stress-induced cardiomyopathy. She received a ketamine infusion as a mental health treatment shortly before the development of symptoms, suggesting that this medication may have precipitated her cardiomyopathy. In recent years, ketamine has become a popular option for treating mental health disorders, including major depressive disorder and substance use disorders. It should be used with caution in patients with known cardiovascular disease, and its cardiac effects warrant further study.

Wild-Type Transthyretin Amyloidosis: A Prevalent and Underdiagnosed Cause of Heart Failure With Preserved Ejection Fraction.

Cardiac amyloidosis is an infiltrative disease characterized by the extracellular deposition of misfolded protein in the myocardium, leading to increased stiffness and an eventual restrictive cardiomyopathy. The slow onset of symptoms and overlap with other cardiomyopathies make prompt diagnosis a challenge. Clinicians should be alerted and include amyloidosis in their differential diagnosis, particularly in patients with heart failure with preserved ejection fraction, unexplained left ventricle hypertrophy, particularly in those shown intolerance to previous antihypertensive medication, and early orthopedic manifestations of the disease such as carpal tunnel syndrome and spinal stenosis. The workup requires the exclusion of monoclonal gammopathies and technetium-99m pyrophosphate nuclear scintigraphy (99mTc-PYP) studies with single-photon emission computerized tomography (SPECT) imaging. Several therapies are now available and can prolong life with significantly improved quality of life, particularly when the diagnosis of amyloidosis is made early. We present the case of a 77-year-old with a delayed diagnosis by five years to highlight the need for heightened clinical suspicion and an appropriate diagnostic algorithm for cardiac amyloidosis.

Anomalous Coronary Artery Identified Post Heart Transplantation.

The following case details a 67-year-old male with a history of heart failure with reduced ejection fraction secondary to cardiac amyloidosis who underwent orthotopic heart transplantation and was later found to have an anomalous left circumflex arising from the right coronary artery in the donor heart.

Optimal Initial Intravenous Loop Diuretic Dosing in Acute Decompensated Heart Failure.

Background: Nearly one-half of patients admitted with acute decompensated heart failure (ADHF) are discharged with unresolved congestion, elevating rehospitalization risk. This may be due to suboptimal intravenous (IV) loop diuretic dosing, which may be influenced by home oral diuretic dose. Objectives: The objective of this study was to determine the association between: 1) home oral loop diuretic dose and optimal initial IV loop diuretic dosing in ADHF; and 2)receiving optimal initial IV loop diuretic dosing and length of stay and 30-day readmission. Methods: Retrospective analysis of adults admitted to a large U.S. hospital for ADHF on home oral loop diuretics from 1 January 2014 to 21 December 2021. Patients were categorized by home dose: low (≤40 mg furosemide equivalents), medium (>40-80 mg furosemide equivalents), and high (>80 mg furosemide equivalents). Optimal initial IV dosing was considered ≥2 times home oral dosing. Poisson regression models estimated prevalence ratios (CIs) for optimal initial IV loop diuretic dosing. Results: Among 3,269 adults admitted for ADHF (mean age 63 years, 62% male), optimal initial IV dosing occurred in 2,218 (67.9%). The prevalence of optimal initial IV dosing among low, medium, and high home dosing was 95.5%, 59.9%, and 4.0%, respectively. Adjusted prevalence ratios for optimal IV dosing with high and medium home dosing, compared to low, were 0.05 (95% CI: 0.03-0.07) and 0.66 (95% CI: 0.62-0.70), respectively. There was no difference in length of stay or 30-day readmission between optimal and suboptimal initial IV diuretic dosing. Conclusions: Among patients with ADHF, higher home loop diuretic dose was strongly associated with a substantially lower likelihood of optimal initial IV diuretic dosing.