Comparative Effectiveness of Psychotherapy vs Antidepressants for Depression in Heart Failure: A Randomized Clinical Trial.

Importance: Heart failure (HF) affects more than 6 million adults in the US and more than 64 million adults worldwide, with 50% prevalence of depression. Patients and clinicians lack information on which interventions are more effective for depression in HF. Objective: To compare the effectiveness of behavioral activation psychotherapy (BA) vs antidepressant medication management (MEDS) on patient-centered outcomes inpatients with HF and depression. Design, Setting, and Participants: This pragmatic randomized comparative effectiveness trial was conducted from 2018 to 2022, including 1-year follow-up, at a not-for-profit academic health system serving more than 2 million people from diverse demographic, socioeconomic, cultural, and geographic backgrounds. Participant included inpatients and outpatients diagnosed with HF and depression, and data were analyzed as intention-to-treat. Data were analyzed from 2022 to 2023. Interventions: BA is an evidence-based manualized treatment for depression, promoting engagement in personalized pleasurable activities selected by patients. MEDS involves the use of an evidence-based collaborative care model with care managers providing coordination with patients, psychiatrists, and primary care physicians to only administer medications. Main Outcomes and Measures: The primary outcome was depressive symptom severity at 6 months, measured using the Patient Health Questionnaire 9-Item (PHQ-9). Secondary outcomes included physical and mental health-related quality of life (HRQOL), measured using the Short-Form 12-Item version 2 (SF-12); heart failure-specific HRQOL, measured using the Kansas City Cardiomyopathy Questionnaire; caregiver burden, measured with the Caregiver Burden Questionnaire for Heart Failure; emergency department visits; readmissions; days hospitalized; and mortality at 3, 6, and 12 months. Results: A total of 416 patients (mean [SD] age, 60.71 [15.61] years; 243 [58.41%] male) were enrolled, with 208 patients randomized to BA and 208 patients randomized to MEDS. At baseline, mean (SD) PHQ-9 scores were 14.54 (3.45) in the BA group and 14.31 (3.60) in the MEDS group; both BA and MEDS recipients experienced nearly 50% reduction in depressive symptoms at 3, 6, and 12 months (eg, mean [SD] score at 12 months: BA, 7.62 (5.73); P < .001; MEDS, 7.98 (6.06); P < .001; between-group P = .55). There was no statistically significant difference between BA and MEDS in the primary outcome of PHQ-9 at 6 months (mean [SD] score, 7.53 [5.74] vs 8.09 [6.06]; P = .88). BA recipients, compared with MEDS recipients, experienced small improvement in physical HRQOL at 6 months (mean [SD] SF-12 physical score: 38.82 [11.09] vs 37.12 [10.99]; P = .04), had fewer ED visits (3 months: 38% [95% CI, 14%-55%] reduction; P = .005; 6 months: 30% [95% CI, 14%-40%] reduction; P = .008; 12 months: 27% [95% CI, 15%-38%] reduction; P = .001), and spent fewer days hospitalized (3 months: 17% [95% CI, 8%-25%] reduction; P = .002; 6 months: 19% [95% CI, 13%-25%] reduction; P = .005; 12 months: 36% [95% CI, 32%-40%] reduction; P = .001). Conclusions and Relevance: In this comparative effectiveness trial of BA and MEDS in patients with HF experiencing depression, both treatments significantly reduced depressive symptoms by nearly 50% with no statistically significant differences between treatments. BA recipients experienced better physical HRQOL, fewer ED visits, and fewer days hospitalized. The study findings suggested that patients with HF could be given the choice between BA or MEDS to ameliorate depression. Trial Registration: ClinicalTrials.gov Identifier: NCT03688100.

The impact of the United Network of Organ Sharing allocation change on waitlist trajectories of inpatients listed with inotropic support: A single-center analysis.

BACKGROUND: In the United Network of Organ Sharing (UNOS) allocation scheme prior to October 18, 2018, heart transplant (HTx) candidates with extracorporeal membrane oxygenation (ECMO), temporary mechanical circulatory support (MCS), or pulmonary artery (PA) catheter inotropic support all received Status 1A priority. In revised scheme, patients with PA catheter and inotropic support are Status 3 after those on ECMO (Status 1) or temporary MCS (Status 2). We examined the impact of the allocation change on HTx candidates listed Status 1A versus Status 3 at a high-volume transplant center. METHODS: Between January 2017 and January 2021, 75 patients were listed with a PA catheter and inotropic support prior to the allocation change (Era 1) and 48 were listed after (Era 2). Clinical characteristics and outcomes were compared for these 123 patients. RESULTS: Heart transplant (HTx) candidates in Era 2 had higher median inotrope doses at listing. There was no significant difference in inpatient wait list days (12 vs. 20 days, P = .15), transition to temporary MCS (33.3% vs. 22.7%, P = .15), or wait list mortality (6.3% vs. 4.0%, P = .68). There was also no significant difference in survival to transplantation (91.7% vs. 94.7%, P = .71). There were no differences in post-transplant outcomes including 1-year survival (88.6% vs. 93.0%, P = .38). CONCLUSION: At a high-volume transplant center, the UNOS allocation change did not result in increased wait list time, use of temporary MCS, or mortality on the waitlist or post-transplant for candidates on inotropic support with continuous hemodynamic monitoring.

Heart transplantation in muscular dystrophy: Single-center analysis.

INTRODUCTION: Cardiac involvement may occur in many forms of muscular dystrophy (MD). While cardiac disease may progress to warrant heart transplantation (HTx), there may be contraindications related to extra-cardiac disease including pulmonary and skeletal muscle involvement that limit overall survival and impairs post-transplant rehabilitation efforts. This study describes the MD HTx experience at a single high-volume center. METHODS: We examined the clinical characteristics and outcomes of patients with MD with heart failure (HF) (n = 28), patients with MD status post HTx (n = 20) and non-MD HTx control group (n = 40) matched 2:1 for age at transplant, sex, listing status, and antibody sensitization. RESULTS: Patients with MD who underwent HTx had increased ventilator days (2 vs. 1 days, p = .013), increased hospital length of stay (20 vs. 12 days, p = .022), and increased discharge to inpatient rehab (60% vs. 8%, p < .001). By 1 year post HTx, patients with MD more often required assistive devices for walking (55% vs. 10%, p = .01). Nonetheless, post-HTx survival was similar at 1 year (100% vs. 97.5%, p = .48) and 5 years (95.0% vs. 87.5%, p = .36). Of the HTx recipients with MD, 95% were followed by a neurologist, 60% by a neuromuscular specialist as part of the Muscular Dystrophy Association Clinic at our center. CONCLUSION: Transplantation is a feasible option for patients with MD and advanced HF. MD patients who undergo transplantation may benefit from multidisciplinary specialized care to optimize MD-related morbidity.

Quantitative Assessment of Cardiac Hypermetabolism and Perfusion for Diagnosis of Cardiac Sarcoidosis.

BACKGROUND: Quantitative assessment of cardiac hypermetabolism from 18Flourodeoxy glucose (FDG) positron emission tomography (PET) may improve diagnosis of cardiac sarcoidosis (CS). We assessed different approaches for quantification of cardiac hypermetabolism and perfusion in patients with suspected CS. METHODS AND RESULTS: Consecutive patients undergoing 18FDG PET assessment for possible CS between January 2014 and March 2019 were included. Cardiac hypermetabolism was quantified using maximal standardized uptake value (SUVMAX), cardiometabolic activity (CMA) and volume of inflammation, using relative thresholds (1.3× and 1.5× left ventricular blood pool [LVBP] activity), and absolute thresholds (SUVMAX > 2.7 and 4.1). Diagnosis of CS was established using the Japanese Ministry of Health and Wellness criteria. In total, 69 patients were studied, with definite or possible CS in 29(42.0%) patients. CMA above 1.5× LVBP SUVMAX had the highest area under the receiver operating characteristic curve (AUC 0.92). Quantitative parameters using relative thresholds had higher AUC compared to absolute thresholds (p < 0.01). Interobserver variability was low for CMA, with excellent agreement regarding absence of activity (Kappa 0.970). CONCLUSIONS: Quantitation with scan-specific thresholds has superior diagnostic accuracy compared to absolute thresholds. Based on the potential clinical benefit, programs should consider quantification of cardiac hypermetabolism when interpreting 18F-FDG PET studies for CS.

High-protein vs. standard-protein diets in overweight and obese patients with heart failure and diabetes mellitus: findings of the Pro-HEART trial.

AIMS: The intermediate-term effects of dietary protein on cardiometabolic risk factors in overweight and obese patients with heart failure and diabetes mellitus are unknown. We compared the effect of two calorie-restricted diets on cardiometabolic risk factors in this population. METHODS AND RESULTS: In this randomized controlled study, 76 overweight and obese (mean weight, 107.8 ± 20.8 kg) patients aged 57.7 ± 9.7 years, 72.4% male, were randomized to a high-protein (30% protein, 40% carbohydrates, and 30% fat) or standard-protein diet (15% protein, 55% carbohydrates, and 30% fat) for 3 months. Reductions in weight and cardiometabolic risks were evaluated at 3 months. Both diets were equally effective in reducing weight (3.6 vs. 2.9 kg) and waist circumference (1.9 vs. 1.3 cm), but the high-protein diet decreased to a greater extent glycosylated haemoglobin levels (0.7% vs. 0.1%, P = 0.002), cholesterol (16.8 vs. 0.9 mg/dL, P = 0.031), and triglyceride (25.7 vs. 5.7 mg/dL, P = 0.032), when compared with the standard-protein diet. The high-protein diet also significantly improved both systolic and diastolic blood pressure than the standard-protein diet (P < 0.001 and P = 0.040, respectively). CONCLUSIONS: Both energy-restricted diets reduced weight and visceral fat. However, the high-protein diet resulted in greater reductions in cardiometabolic risks relative to a standard-protein diet. These results suggest that a high-protein diet may be more effective in reducing cardiometabolic risk in this population, but further trials of longer duration are needed.

The impact of depression on heart transplant outcomes: A retrospective single-center cohort study.

BACKGROUND: Depression is prevalent in patients with heart failure and after heart transplant. We identified the prevalence of pre- and post-transplant depression and its association with clinical characteristics and post-transplant outcomes. METHODS: We reviewed 114 adults transplanted 1/1/2015 to 12/31/2015 and identified patients with pre- and post-transplant depression. Clinical characteristics and outcomes were compared. RESULTS: Of 114 patients, 35.1% had pre-transplant depression and 26.3% had post-transplant depression. Patients with post-transplant depression within the first year were significantly more likely to have acute rejection (10% vs 0%), longer intensive care unit (11.7 days vs 7.8 days) and hospital stay (31.7 days vs 16.3 days), and discharge to inpatient rehabilitation (26.7% vs 8.3%). Patients with post-transplant depression within the first year had significantly higher 5-year mortality (30% vs 9.5%, p = .009). However, after adjustment for total artificial heart/biventricular assist device, acute rejection, intensive care unit, and hospital length of stay, this relationship was no longer significant (HR 2.11; 95% CI 0.18-25.27; p = .556). CONCLUSIONS: Depression is common among heart transplant candidates and recipients. While pre-transplant depression did not impact outcomes, patients with post-transplant depression were more likely to have had a complicated course, suggesting the need for increased vigilance regarding depression in such patients.

Impact of the United Network for organ sharing 2018 donor heart allocation system on transplant morbidity and mortality.

BACKGROUND: While the revised UNOS HTx donor allocation system aimed to minimize waitlist mortality by prioritizing more critically ill transplant candidates, there is concern for increased post-transplant morbidity and mortality. We examined the impact of the revised allocation system on waitlist and post-transplant outcomes at a high-volume transplant center. METHODS: One hundred and sixty nine adult patients underwent first-time single-organ HTx one year before (Era 1:79 patients) and after (Era 2:90 patients) implementation of the new allocation system (10/18/2018). Clinical characteristics, waitlist outcomes, and post-transplant morbidity and mortality were compared. RESULTS: Era 2 patients were twice as likely to be transplanted on temporary mechanical circulatory support (43% vs. 19%, p < .0001). While Era 2 waitlist time was shorter (10 vs. 43 days, p < .001), exception status requests (21.1% vs. 17.9%) and waitlist mortality (3.3% vs. 2.2%) were similar. There was no difference in primary graft dysfunction, intensive care unit or hospital length of stay, readmissions, rejection, allograft vasculopathy, or 1-year survival (91.1% vs. 93.7%). CONCLUSIONS: In a high-volume center, the revised HTx allocation system shortened waitlist time with no significant change in waitlist mortality or observed impact on post-transplant outcomes. With careful patient selection, the revised allocation system may optimize waitlist and post-transplant outcomes.

Heart failure with preserved ejection fraction: Similarities and differences between women and men.

The syndrome of heart failure (HF) with preserved ejection fraction (HFpEF) is now recognized to account for up to half of HF cases and is the dominant form of HF in older adults, especially women. Multiple factors conspire in this predilection of HFpEF for older women. This review will discuss the epidemiology, pathophysiology, prognosis, and treatment of HFpEF with emphasis on the similarities and differences in cardiovascular aging changes, and the differential impact of comorbidities in women versus men. Responses to pharmacologic and lifestyle interventions are also reviewed. We conclude by suggesting future directions for both prevention and treatment of this common and highly morbid cardiovascular disorder.

Acute Postpartum Heart Failure With Preserved Systolic Function.

Dyspnea in the postpartum period can be a symptom of a wide range of causes spanning normal pregnancy to life-threatening pathology. We describe a case of acute postpartum heart failure with preserved systolic function in the absence of pre-eclampsia or prior cardiovascular disease. (Level of Difficulty: Beginner.).

Combined heart and kidney transplantation-Is there a protective effect against cardiac allograft vasculopathy using intravascular ultrasound?

BACKGROUND: Because cardiac and renal disease are physiologically related and often coexist, the prevalence of combined heart and kidney transplantation (HKTx) has significantly increased over the last few years. It has been suggested that combined organ allografts modulate the immune system favorably for one or both allografts resulting in successful clinical outcomes. However, whether the addition of kidney transplantation has a protective immune effect against developing cardiac allograft vasculopathy (CAV) has not been fully investigated. METHODS: From March 2010 to September 2018, 30 HKTx recipients who had baseline (4-6 weeks) and 1-year intravascular ultrasound (IVUS) were matched with 60 isolated heart transplant (HTx-alone) recipients using propensity scores. First-year changes in maximal intimal thickness (MIT), maximal intimal area (MIA), maximal percent stenosis (MPS), percent atheroma volume (PAV), and incidence of rapid plaque progression were compared between the groups. RESULTS: First-year coronary plaque progression was significantly decreased in HKTx recipients compared with HTx-alone recipients by change in the MIT (0.11 ± 0.14 mm vs 0.40 ± 0.32 mm, p < 0.001), MIA (0.52 ± 1.52 mm2 vs 1.86 ± 2.68 mm2, p = 0.002), MPS (2.10% ± 5.64 percentage points vs 7.22% ± 8.59 percentage points, p = 0.001), and PAV (1.62% ± 3.07 percentage points vs 5.90% ± 5.92 percentage points, p < 0.001). Rapid plaque progression occurred in 2 of 30 in HKTx (6.7%) and in 22 of 60 HTx alone (36.7%), p = 0.002. CONCLUSIONS: Combined heart and kidney transplantation is associated with a decrease in CAV by coronary plaque progression on IVUS. These results suggest that HKTx may have an immune modulating benefit over HTx alone.

Does ex vivo perfusion lead to more or less intimal thickening in the first-year post-heart transplantation?

BACKGROUND: The Organ Care System (OCS), an ex vivo heart perfusion platform, represents an alternative to the current standard of cold organ storage that sustains the donor heart in a near-physiologic state. Previous reports showed that this system had significantly shortened the cold ischemic time from standard cold storage (CS). However, the effect of reduced ischemic injury against the coronary vascular bed has not been examined by intravascular ultrasound (IVUS). METHODS: Between August 2011 and February 2013, heart transplant (HTx) candidates enrolled in the PROCEED 2 trial were randomized to either CS or OCS. IVUS was performed at 4-6 weeks (baseline) and repeated 1 year after transplantation. The change in maximal intimal thickness (MIT) and other clinical outcomes were examined. RESULTS: Thirty-nine patients were randomized and underwent HTx by OCS (n=16) or CS (n=18). Of these, 18 patients (OCS: n=5, CS: n=13) with paired IVUS were examined. There were no significant differences in the change of MIT and other clinical outcomes between the groups. CONCLUSION: The incidence of cardiac allograft vasculopathy in donor hearts preserved with the OCS versus CS was similar. These results suggest that this ex vivo allograft perfusion system is a promising and valid platform for donor heart transportation.

Takayasu's Arteritis Presenting as Heart Failure in a 19-Year-Old Female.

This report presents the case of this atypical presentation of a rare disease in a 19-year-old female with cardiomyopathy and hypertension. Investigation revealed renovascular stenosis, infarcts, and active vasculitis pathognomonic for Takayasu arteritis (TA). Cardiac magnetic resonance imaging demonstrated mild pericardial inflammation and epicardial edema. Vasculitis-induced renovascular secondary hypertension resulted in myocardial dysfunction, which recovered with treatment of hypertension and TA. (Level of Difficulty: Beginner.).

Allogeneic mesenchymal precursor cells (MPCs): an innovative approach to treating advanced heart failure.

INTRODUCTION: Over 37 million people worldwide are living with Heart Failure (HF). Advancements in medical therapy have improved mortality primarily by slowing the progression of left ventricular dysfunction and debilitating symptoms. Ultimately, heart transplantation, durable mechanical circulatory support (MCS), or palliative care are the only options for patients with end-stage HF. Regenerative therapies offer an innovative approach, focused on reversing myocardial dysfunction and restoring healthy myocardial tissue. Initial clinical trials using autologous (self-donated) bone marrow mononuclear cells (BMMCs) demonstrated excellent safety, but only modest efficacy. Challenges with autologous stem cells include reduced quality and efficacy with increased patient age. The use of allogeneic mesenchymal precursor cells (MPCs) offers an "off the shelf" therapy, with consistent potency and less variability than autologous cells. AREAS COVERED: Preclinical and initial clinical trials with allogeneic MPCs have been encouraging, providing the support for a large ongoing Phase III trial-DREAM-HF. We provide a comprehensive review of preclinical and clinical data supporting MPCs as a therapeutic option for HF patients. EXPERT OPINION: The current data suggest allogeneic MPCs are a promising therapy for HF patients. The results of DREAM-HF will determine whether allogeneic MPCs can decrease major adverse clinical events (MACE) in advanced HF patients.

Regulation of HBV-specific CD8(+) T cell-mediated inflammation is diversified in different clinical presentations of HBV infection.

Chronic HBV infection is the leading cause of liver cirrhosis and hepatic cancer, but the individual responses toward HBV infection are highly variable, ranging from asymptomatic to chronic active hepatitis B inflammation. In this study, we hypothesized that the different individual responses to HBV infection was associated with differences in HBV-specific CD8(+) T cell-mediated inflammation and cytotoxicity. Blood samples were collected from subjects with asymptomatic HBV-infection, subjects undergoing active chronic HBV flares (active CHB), and subjects with HBV-infected hepatocellular carcinoma (HBV-HCC). By tetramer staining, we found that all three groups had similar frequencies of HBVspecific CD8(+) T cells. However, after HBV peptide stimulation, the HBV-specific CD8(+) T cells in asymptomatic subjects had significantly stronger interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), and CD107a expression than those in active CHB and HBV-HCC patients. Examination of surface marker expression revealed that the PD-1(-)Tim-3(-) double-negative cell population was the main contributor to HBV-specific inflammation. In active CHB patients and HBV-HCC patients, however, the frequencies of activated PD-1(-)Tim-3(-) cells were significantly reduced. Moreover, the serum HBV DNA titer was not correlated with the frequencies of HBV-specific CD8(+) T cells but was inversely correlated with the frequencies of IFN-g-expressing and CD107a-express cells in response to HBV stimulation. Together, our data demonstrated that the status of HBVspecific CD8(+) T cell exhaustion was associated with different clinical outcomes of chronic HBV infection.

Tricuspid Regurgitation, the Forgotten Valvular Lesion-A Contemporary Review of Etiology, Prevalence, and Management Options.

Tricuspid regurgitation (TR) is a common finding. Pathologic TR is an independent risk factor for mortality. TR can be classified by etiology into functional versus organic. Organic TR is caused by structural damage to the tricuspid valve (TV) by a spectrum of etiologies, including pacemaker leads and right heart biopsies, whereas functional TR is predominantly due to elevated pulmonary pressures. Atrial fibrillation and chamber enlargement, among other risk factors, are strong predictors of functional TR. Correction of elevated pulmonary pressures improves TR, and concurrent repair of severe TR at the time of left heart valve surgery improves postoperative heart failure symptoms but does not improve survival. TR repair is associated with less operative and long-term mortality than TV replacement, and demonstrates similar improvements in heart failure symptoms. Substantial residual TR remains after repair, and reoperative mortality for residual TR is considerable. Percutaneous TV replacement may offer a rescue strategy.

Regional hippocampal damage in heart failure.

AIMS: Heart failure (HF) patients show cognitive and mood impairments, including short-term memory loss and depression, that have an adverse impacting on quality of life and self-care management. Brain regions, including the hippocampus, a structure significantly involved in memory and mood, show injury in HF, but the integrity of specific hippocampal subregions is unclear. METHODS AND RESULTS: To assess regional hippocampal volume loss, we evaluated 17 HF patients (mean age ± SD, 54.4 ± 2.0 years; 12 male, left ventricular ejection fraction 28.3 ± 6.8%; New York Heart Association class II/III 94%/6%) and 34 healthy control subjects (52.3 ± 1.3 years; 24 male) using high-resolution T1-weighted magnetic resonance imaging and evaluated localized surface changes with morphometric procedures. Hippocampi were manually outlined, and volumes calculated from normalized tracings. Volume differences between groups were assessed by two-sample t-tests, and regional differences were assessed by surface morphometry. Patients with HF exhibited smaller hippocampal volumes than controls (right 3060 ± 146 mm(3) vs. 3478 ± 94 mm(3), P = 0.02; left 3021 ± 145 mm(3) vs. 3352 ± 98 mm(3), P = 0.06). Volume reductions were detected principally in CA1, an area integral to an array of learning and memory functions, as well as in mid to posterior CA3 and subiculum. CONCLUSION: The hippocampus shows regional volume reduction in HF, which may contribute to short-term memory loss and depression associated with the condition.