Heart Failure Research Articles

"Real-life" Data of Zanubrutinib in Patients with Waldenström Macroglobulinemia - A Multi-Center Retrospective Study.

Waldenström macroglobulinemia (WM) is a rare indolent lymphoma. Zanubrutinib (ZAN), a second-generation BTK inhibitor, has been approved for the treatment of WM in any line of therapy in 2021. Between November 2020 and January 2022, an expanded access program of ZAN opened in Israel for the treatment of patients with relapsed refractory (RR)-WM or those ineligible for chemotherapy or ibrutinib in first line. This is a multi-center retrospective study aiming to provide real-world data on ZAN in patients with WM in Israel. Demographic and clinical data were collected and coded from electronic files. Response was evaluated by the investigator's assessment. As the program closed, patients transitioned to commercial ZAN. 13 patients (12 RR; 1 treatment-naive) were enrolled across 8 centers in Israel. The median age at ZAN initiation was 71 years (range, 50-85); 6 were males; 10 had high IPSS-WM. RR pts had a median of 1 (1-4) prior lines of therapy. Other than progressive disease after chemoimmunotherapy (CIT), the most common considerations for choosing ZAN were patients' age and/or comorbidities (n=5), as well as ibrutinib toxicity. The initial ZAN dose was reduced in 4 pts. The median time on ZAN was 19.5 months (2.9-29.5). Of 12 evaluable patients, the ORR was 83% with 3 minor responses, 6 PR, and 1 VGPR. With a median follow-up of 19.6 months, 7 patients were still on ZAN, 5 progressed, 4 while on ZAN, and 1 after ZAN was stopped due to AE. 18 months PFS and OS were 60.5% and 77%, respectively. Eight (61%) patients had AEs of any grade, and 3 (23%) of grade 3-4; 2 stopped ZAN due to congestive heart failure and extreme fatigue. The results of this real-world high-risk population are consistent with prospective studies highlighting the efficacy and safety of ZAN.

Concurrent Onset of Osimertinib-Induced Heart Failure and Metronidazole-Induced Encephalopathy During Brain Abscess Treatment: A Report of a Rare Case

Concurrent Onset of Osimertinib-Induced Heart Failure and Metronidazole-Induced Encephalopathy During Brain Abscess Treatment: A Report of a Rare Case

Association between frailty and adverse outcomes after cardiac resynchronization therapy: a systematic review and meta-analysis.

To synthesize evidence, using data from published studies, on the association of frailty with the outcomes after cardiac resynchronization therapy (CRT). The systematic search of PubMed, Web of Science, Scopus, and Embase databases was done to identify observational studies (cohort/case-control/cross-sectional) that used an objective method for frailty assessment and had presented adjusted effect sizes. STATA version 15.0 was used to conduct analysis, which was based on random effects model. Fifteen studies were included. Frailty was found to be associated with an increased risk of in-hospital mortality (odds ratio (OR) 6.96, 95% confidence interval (CI) 5.48, 8.85). The effect of frailty on the response to CRT was not statistically significant (OR 0.55, 95% CI 0.19, 1.59). The pooled effect size indicated that frailty was associated with somewhat bigger but not statistically significant increase in the risk of complications (OR 1.70, 95% CI 0.93, 3.12). The risks of mortality and decompensated heart failure on long-term follow up were higher in frail patients (Hazard ratio (HR) 1.75, 95% CI 1.40, 2.17 and HR 3.03, 95% CI 1.33, 6.90, respectively) compared to patients without frailty. The risk of readmission was higher in frail patients, however, it did not achieve statistical significance (HR 2.63, 95% CI 0.89, 7.75). Frail CRT patients could be at higher risks of mortality, decompensated heart failure, and may have potentially higher rates of complications. Integrating frailty assessment into pre-CRT evaluation and customizing interventions for frail patients might be an essential steps towards enhancing outcomes in this population.

Validation of Psychometric Properties of Partners in Health Scale for Heart Failure

Background: Congestive heart failure (CHF) is a complex chronic disease, and it is associated with a second comorbid condition in more than half of cases. Self-management programs can be specific to CHF or generic for chronic diseases. Several tools have been validated for CHF. Presently, there are no established generic instruments that are validated for measuring self-management in CHF. Objective: This study aims to evaluate the internal reliability and construct validity (psychometric properties) of the Partners in Health (PIH) scale for patients with congestive heart failure, a generic chronic disease self-management tool. Methods: The study included 210 adult CHF patients [120 with heart failure with reduced ejection fraction (HfrEF), 90 with preserved ejection fraction (HfpEF)], from Community Cardiology Outpatients in West Melbourne, Australia, who were treated in community cardiology and were included between May 2022 and Jan 2024. The screened patient population were diagnosed with CHF and were eligible for an SGLT-2 inhibitor. Cohort analysis used the Bayesian confirmatory factor analysis to evaluate the a priori four-factor structure. Omega coefficients and 95% credible intervals (CI) were used to assess internal reliability. Results: In the CHF (HFrEF) and preserved ejection fraction (HFpEF) cohorts, participants’ mean [standard deviation (SD)] age was 66.8 (13.5) and 71.3 (9.76) years. Description of study sociodemographics highlighted that 88% and 52% of patients were male, there was a BMI > 50% in both cohorts, eGFR > 60 mL/min were 59% and 74%, and LVEF < 40% and > 50% were 99% and 100%, respectively. Model fit for the hypothesised model was adequate (posterior predictive p = 0.073) and all hypothesised factor loadings were substantial (>0.6) and significant (p < 0.001). Omega coefficients (95% CI) for the PIH subscales of Knowledge, Partnership, Management and Coping were 0.84 (0.79–0.88), 0.79 (0.73–0.84), 0.89 (0.85–0.91) and 0.84 (0.79–0.88), respectively. Conclusion: This study is original in confirming the dimensionality, known-group validity, and reliability of the PIH scale for measuring generic self-management in outpatients with CHF syndrome.

Cigarette Smoking, Smoking Cessation, and Heart Failure Subtypes: Insights From the Jackson Heart Study.

Cigarette smoking has been associated with incident heart failure (HF). However, the association between cigarette smoking and smoking cessation with HF subtypes has not been well elucidated, particularly among Black people. We investigated 4189 (never smoker n=2934, former smoker n=761, current smoker n=464) Black participants (mean age 54 years, 64% women) without a history of HF or coronary heart disease at baseline in the Jackson Heart Study. We examined the association of cigarette smoking with incident HF hospitalization and HF subtypes (HF with preserved ejection fraction and HF with reduced ejection fraction). After adjustment for confounding factors, current smoking was associated with incident HF (both subtypes) compared with never smoking. Smoking intensity among those who identified as currently smoking and smoking burden among those who ever smoked were associated with higher incidence of HF with preserved ejection fraction compared with never smoking. Lung function evaluated by spirometry at baseline did not significantly influence these associations. The risk of developing HF decreased with more years after smoking cessation, and more than 20 years of smoking cessation were required to reach a risk comparable to that of never smoking. Smoking cigarettes was associated with developing both subtypes of HF and it was independent from the influences on baseline lung function. Long-term smoking cessation is necessary to prevent the onset of HF in people who smoke cigarettes.

Prognostic value of advanced lung cancer inflammation index in heart failure patients: A comprehensive analysis.

The prognosis of heart failure (HF) is closely linked to inflammation and nutritional status. The advanced lung cancer inflammation index (ALI) is a composite indicator consisting of several parameters used to assess inflammation and nutritional status. Our study aimed to investigate the prognostic value of ALI in HF patients. The data from Study 1, which included 1359 HF patients, were extracted from the National Health and Nutrition Examination Survey (NHANES) database spanning the years 1999 to 2018. Study 2 analysed data from patients with HF who underwent cardiac magnetic resonance imaging examinations from 2020 to 2023. Kaplan-Meier curve analysis, Cox proportional hazard model, time-dependent receiver operating characteristic (ROC) curve and restricted cubic spline (RCS) were used to evaluate the relationship between ALI and long-term prognosis of patients with HF in Study 1. Logistic regression analysis was used to evaluate the correlation between ALI and left ventricular reverse remodelling, and RCS was used to determine any dose-response relationship. Spearman correlation was used to evaluate the relationship between ALI and indicators of cardiac structural changes. Study 1 found that the average age of the patients was 68years [inter-quartile range (IQR) 58-76], the proportion of males was 54.3%, and there were 699 all-cause mortality and 293 cardiovascular mortality cases. After adjusted by multivariable Cox regression analysis, elevated ALI levels were significantly associated with increased risks of all-cause [hazard ratio (HR)=0.58, 95% confidence interval (CI)=0.42-0.79, P<0.001] and cardiovascular mortality (HR=0.61, 95% CI=0.38-0.97, P=0.036) in patients with HF. A linear negative correlation was observed between ALI and both all-cause (P=0.0011 and P<0.001, P for nonlinear=0.3993) and cardiovascular mortality (P=0.0011, P for nonlinear=0.5198). Time-dependent ROC curves showed the predictive value of ALI for all-cause mortality [area under the curve (AUC)=0.678 in 3years, AUC=0.674 in 5years and AUC=0.683 in 10years] and cardiovascular mortality (AUC=0.694 in 3years, AUC=0.685 in 5years and AUC=0.697 in 10years). Study 2 included 79 patients; the average age of the patients was 44years (IQR 35-55); and the proportion of males was 74.7%. Adjusted multivariable logistic regression analysis indicated that high ALI levels were associated with left ventricular reverse remodelling (LVRR) in patients with HF following discharge from the hospital [odds ratio (OR)=3.16, 95% CI=1.06-10.8, P=0.049]. Spearman analysis revealed a correlation between ALI and extracellular volume (ECV) (r=-0.25, P=0.023). ALI is associated with all-cause and cardiovascular mortality risk and structural changes in the heart in patients with HF.

Integrating Out-of-Pocket Costs Into Shared Decision-Making for Heart Failure With Reduced Ejection Fraction: A Stepped-Wedge Trial (POCKET-COST-HF).

Guideline-directed medical therapy for heart failure (HF) with reduced ejection fraction can entail high out-of-pocket (OOP) costs, prompting concerns about financial toxicity and access. OOP costs are generally unavailable during encounters. This trial assessed the impact of providing patient-specific OOP costs to patients and clinicians. This trial was conducted between June 2021 and August 2023 at 6 clinics in 2 health systems using a stepped-wedge, clinic-level cluster-randomized design. Adult patients with HF with reduced ejection fraction (left ventricular ejection fraction ≤40%) were enrolled. The intervention was built upon the EPIC-HF (Electronically Delivered, Patient-Activation Tool for Intensification of Medications for Chronic Heart Failure with Reduced Ejection Fraction) checklist of approved HF with reduced ejection fraction medications. Patients and clinicians received this checklist with (intervention) or without (control) patient-specific OOP cost estimates for higher-cost medications at the time of encounter. Estimates were obtained by providing pharmacy benefit information to a financial navigation firm. Encounters were audio-recorded, and patients were surveyed 2 weeks later. The primary outcome was cost-informed decision-making, defined by mentioning HF medication cost during the encounter. The primary analysis used a generalized linear mixed model. Secondary outcomes were assessed via transcript subcoding and analysis of survey responses. Demographic characteristics of 247 patients (mean age, 62.9 years; 29.5% female; 26.3% Black; and 3.2% Hispanic/LatinX) treated by 39 clinicians in intervention and control periods were similar. In the primary model, the rate of cost-informed decision-making was higher in the intervention group than the control group (68% versus 49%; P=0.021). Baseline rates of cost discussions and the impact of the intervention varied across sites. When cost discussions were present, fewer discussions in the intervention group involved contingency plans to address potential costs (16.5% versus 31.9%; P=0.028). Most other secondary outcomes were not significantly different. Disclosing comprehensive OOP medication costs to patients with HF with reduced ejection fraction increased cost-informed decision-making. Further work is needed to optimize implementation and assess the impact on medication choices and adherence. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04793880.

Out-of-Hospital Cardiac Arrest: Does a History of Myocarditis/Perimyocarditis Affect the Outcome? A Swedish Nationwide Study.

Acute myocarditis/perimyocarditis presents with a variable prognosis ranging from complete recovery to end-stage heart failure (HF), sudden cardiac arrest, and death. The relationship between a prior history of myocarditis/perimyocarditis and outcomes in out-of-hospital cardiac arrest remains unclear. Using the SCRR (Swedish Cardiopulmonary Resuscitation Registry), we analyzed 54 568 cases of out-of-hospital cardiac arrest from 2010 to 2020 where cardiopulmonary resuscitation was attempted. Patients with a history of myocarditis/perimyocarditis were compared with those without in terms of characteristics and survival. Four hundred ninety-eight patients (0.9%) had a history of myocarditis/perimyocarditis. These patients were predominantly men (73.8%), had an average age of 68 years, displayed a higher prevalence of cardiovascular comorbidities, and more frequently displayed shockable initial rhythms (28.7% versus 23.1%). Prior myocarditis/pericarditis did not correlate with worse short-term (odds ratio [OR], 0.91 [95% CI, 0.61-1.33]) or long-term survival (hazard ratio [HR], 1.01 [95% CI, 0.91-1.13]). Patients with myocarditis/perimyocarditis with concomitant HF showed worse long-term survival in unadjusted analyses. Adjusted analyses confirmed that absence of HF was linked to improved short-term survival (OR, 1.46 [95% CI, 1.32-1.62]), whereas prevalence of HF was a predictor for worsened long-term survival (HR, 0.91 [95% CI, 0.91-0.95]) after out-of-hospital cardiac arrest. Analyses were adjusted for myocarditis/perimyocarditis, sex, age, HF, time to cardiopulmonary resuscitation start, and initial rhythm. Prior myocarditis/perimyocarditis per se did not contribute to a worsened outcome following out-of-hospital cardiac arrest. However, the presence of concomitant HF was linked to unfavorable short- and long-term outcomes.

Traditional Chinese medicine for cardiovascular disease: efficacy and safety

In China and other Asian nations, traditional medicine has long been utilized in the treatment of cardiovascular diseases (CVD). While Chinese authorities have incorporated traditional Chinese medicine (TCM) treatment experiences as a supplementary guide for CVD, its international recognition remains limited due to a scarcity of high-quality and reliable randomized controlled trials (RCTs) evidence. The purpose of this study was to examine the clinical outcomes with TCM for CVD after the recent publication of large trials adding &amp;gt;20,000 individuals to the published data. Here, we systematically reviewed 55 published RCTs (modified Jadad scores &amp;gt; 4) in the past 20 years, involving a total of 36,261 patients. In most studies, TCM has been associated with significant improvements in alternative endpoints such as hypertension, coronary heart disease, stroke and heart failure. A total of 19 trials reported on primary outcomes such as cardiovascular events and death events. During the follow-up period, some Chinese patent medicines can effectively reduce the “hard” endpoints of coronary heart disease, stroke, and heart failure, the overall trend of cardiovascular outcomes is lower. The risk of adverse effects was not significantly increased compared to the control group, suggesting its potential as an alternative approach for primary and secondary prevention of CVD based on the available evidence.

Focus on the comorbidities of heart failure: the importance of multidisciplinary management

The diagnosis and treatment of heart failure comorbidities present a significant clinical challenge, as these comorbidities significantly affect patient prognosis. The causes of heart failure comorbidities are complex, and the underlying mechanisms are not fully understood. Moreover, traditional heart failure management methods are inadequate in addressing these issues. Improving the management and treatment of comorbidities can significantly enhance patient quality of life and prognosis. This requires clinicians to have a comprehensive understanding of heart failure and its comorbidities and to be capable of devising effective treatment plans. Multidisciplinary management should be utilized to create individualized treatment plans for heart failure patients to better address the challenges of multiple comorbidities. Clinicians need to have a broad perspective and employ systematic approaches to improve treatment outcomes. This article emphasizes the importance of individualized and multidisciplinary management strategies in the treatment of heart failure comorbidities, aiming to provide a systematic solution to enhance patient quality of life and improve prognosis.

Advancing 3D Engineered In Vitro Models for Heart Failure Research: Key Features and Considerations

Heart failure is characterized by intricate myocardial remodeling that impairs the heart’s pumping and/or relaxation capacity, ultimately reducing cardiac output. It represents a major public health burden, given its high prevalence and associated morbidity and mortality rates, which continue to challenge healthcare systems worldwide. Despite advancements in medical science, there are no treatments that address the disease at its core. The development of three-dimensional engineered in vitro models that closely mimic the (patho)physiology and drug responses of the myocardium has the potential to revolutionize our insights and uncover new therapeutic avenues. Key aspects of these models include the precise replication of the extracellular matrix structure, cell composition, micro-architecture, mechanical and electrical properties, and relevant physiological and pathological stimuli, such as fluid flow, mechanical load, electrical signal propagation, and biochemical cues. Additionally, to fully capture heart failure and its diversity in vivo, it is crucial to consider factors such as age, gender, interactions with other organ systems and external influences—thereby recapitulating unique patient and disease phenotypes. This review details these model features and their significance in heart failure research, with the aim of enhancing future platforms that will deepen our understanding of the disease and facilitate the development of novel, effective therapies.

Low dose threshold for measuring cardiac functional metrics using four-dimensional CT with deep learning.

Four-dimensional CT is increasingly used for functional cardiac imaging, including prognosis for conditions such as heart failure and post myocardial infarction. However, radiation dose from an acquisition spanning the full cardiac cycle remains a concern. This work investigates the possibility of dose reduction in 4DCT using deep learning (DL)-based segmentation techniques as an objective observer. A 3D residual U-Net was developed for segmentation of left ventricle (LV) myocardium and blood pool. Two networks were trained: Standard DL (trained with only standard-dose [SD] data) and Noise-Robust DL (additionally trained with low-dose data). The primary goal of the proposed DL methods is to serve as an unbiased and consistent observer for functional analysis performance. Functional cardiac metrics including ejection fraction (EF), global longitudinal strain (GLS), circumferential strain (CS), and wall thickness (WT), were measured for an external test set of 250 Cardiac CT volumes reconstructed at five different dose levels. Functional metrics obtained from DL segmentations of standard dose images matched well with those from expert manual analysis. Utilizing Standard-DL, absolute difference between DL-derived metrics obtained with standard dose data and 100mA (corresponding to ∼76±13% dose reduction) data was less than 0.8±1.0% for EF, GLS, and CS, and 5.6±6.7% for Average WT. Performance variation of Noise-Robust DL remained acceptable at even 50mA. We demonstrate that on average radiation dose can be reduced by a factor of 5 while introducing minimal changes to global functional metrics (especially EF, GLS, and CS). The robustness to reduced image quality can be further boosted by using emulated low-dose data in the DL training set.

Cross-species single-cell RNA-seq analysis reveals disparate and conserved cardiac and extracardiac inflammatory responses upon heart injury

The immune system coordinates the response to cardiac injury and controls regenerative and fibrotic scar outcomes in the heart and subsequent chronic low-grade inflammation associated with heart failure. Adult mice and humans lack the ability to fully recover while adult zebrafish spontaneously regenerate after heart injury. Here we profile the inflammatory response to heart cryoinjury in zebrafish and coronary artery ligation in mouse using single cell transcriptomics. We interrogate the extracardiac reaction to cardiomyocyte necrosis to assess the specific peripheral tissue and immune cell reaction to chronic stress. Cardiac macrophages play a critical role in determining tissue homeostasis by healing versus scarring. We identify distinct transcriptional clusters of monocytes/macrophages (mono/Mϕ) in each species and find analogous pairs in zebrafish and mice. However, the reaction to myocardial injury is largely disparate between mice and zebrafish. The dichotomous response to heart damage between the murine and zebrafish mono/Mϕ and/or the presence of distinct zebrafish mono/Mϕ subtypes may underlie the impaired regenerative process in adult mammals and humans. Our study furnishes a direct cross-species comparison of immune responses between regenerative and profibrotic myocardial injury models, providing a useful resource to the fields of regenerative biology and cardiovascular research.

Potential effects of beta-blockers in HFpEF.

Heart failure with preserved ejection fraction (HFpEF) poses a significant challenge in contemporary medicine, characterized by poor quality of life, high healthcare costs, and increased mortality. Despite advancements in medical research, treatment strategies for HFpEF remain elusive, with unclear guidance on the use of beta-blockers. While sympathetic overstimulation is common in HFpEF, beta-blockers, though potentially beneficial in reducing sympathetic activity, may exacerbate chronotropic incompetence and decrease exercise tolerance. Additionally, their impact on outcomes in HFpEF patients with concurrent atrial fibrillation is uncertain. Some studies suggest the potential benefits of beta-blockers on diastolic function, yet evidence on clinical endpoints remains inconclusive. Recent research indicates a potential reduction in all-cause mortality with beta-blocker use in HFpEF, although their effect on combined mortality or HF hospitalizations is less clear. Moreover, beta-blocker efficacy may vary depending on ejection fraction subgroups, with more favorable outcomes observed in HFmrEF compared to HFpEF. Current literature underscores the need for large-scale randomized clinical trials to clarify the role of beta-blockers in HFpEF management. Given the limitations of existing evidence, future research is essential to inform updated treatment guidelines and therapeutic protocols tailored to the contemporary clinical landscape.

Clinical features and quality of life in patients with Fabry disease

To explore the clinical characteristics of patients with Fabry disease (FD) and the potential influencing factors, as well as to analyze the main factors affecting the quality of life (QOL) of FD patients. The clinical data of 21 adult FD patients who were hospitalized and treated at the University of Hong Kong-Shenzhen Hospital from January 2022 to December 2023 were retrospectively analyzed, including questionnaire data from 17 of these patients. The total score of the Short Form 36 Health Survey (SF-36) was used to determine the QOL. The patient's average age was (42±9) years, including 13 males (61.9%). All patients belonged to 17 families and had a total of 14 gene mutation types. The c.640-801G>A mutation was the most common type, found in 4 patients (19.0%), with cardiac damage as the primary manifestation. The c.901C>T mutation led to lesions in the heart, brain, and kidneys, and early onset and severe phenotypes were detected in female patients. Male patients had lower total SF-36 scores than females (P<0.05). Patients with proteinuria, stroke, hypohidrosis/anhidrosis, and cardiac insufficiency had lower total SF-36 scores compared with those without these symptoms (all P<0.05). The current study indicates that the clinical phenotypes of patients with FD are influenced by a combination of gender, genotype, and non-genetic factors, and gender and clinical symptoms serve as the primary factors affecting patient's QOL.

Contribution of point-of-care ultrasound in the prehospital management of patients with non-trauma acute dyspnea: a systematic review and meta-analysis.

Acute dyspnea is a common symptom whose management is challenging in prehospital settings. Point-of-care ultrasound (POCUS) is increasingly accessible because of device miniaturization. To assess the contribution of POCUS in the prehospital management of patients with acute nontraumatic dyspnea, we performed a systematic review on nontrauma patients of any age managed in the prehospital setting for acute dyspnea and receiving a POCUS examination. We searched seven databases and gray literature for English-language studies published from January 1995 to November 2023. Two independent reviewers completed the study selection, data extraction, and risk of bias assessment. The primary outcome was the assessment of the contribution of POCUS to feasibility, diagnostic, therapeutic, prognosis, patient referral, and transport vector modification. Twenty-three studies were included. The risk of bias assessment identified 3 intermediate-risk, 18 serious-risk, and 2 critical-risk studies. Three studies reported moderate to excellent feasibility for lung POCUS, and three studies reported poor to mediocre feasibility for cardiac POCUS. The median duration of the POCUS examination was less than 5 minutes (six studies). POCUS improved diagnostic identification (seven studies). The diagnostic accuracy of POCUS was excellent for pneumothorax (sensitivity = 100%, specificity = 100%, two studies), very good for acute heart failure (sensitivity = 71-100%, specificity = 72-95%, eight studies), good for pneumonia (sensitivity = 88%, specificity = 59%, one study), and moderate for pleural effusion (sensitivity = 26-53%, specificity = 83-92%, two studies). Treatment was modified in 11 to 54% of the patients (seven studies). POCUS had no significant effect on patient prognosis (two studies). POCUS contributed to patient referrals and transport vectors in 51% (four studies) and 25% (three studies) of patients, respectively. The evidence supports the use of POCUS for managing acute nontraumatic dyspnea in the prehospital setting in terms of feasibility, overall diagnostic contribution, and, particularly, lung ultrasound for acute heart failure diagnosis. Moreover, POCUS seems to have a therapeutic contribution. There is not enough evidence supporting the use of POCUS for pneumonia, pleural effusion, pneumothorax, chronic obstructive pulmonary disease, or asthma exacerbation diagnosis, nor does it support prognostic, patient referral, and transport vector contribution. A high level of evidence is lacking and needed.

Letter by Yang and Zhang Regarding Article, “Clinical Impact of Routine Assessment of Patient-Reported Health Status in Heart Failure Clinic: The PRO-HF Trial”

Letter by Yang and Zhang Regarding Article, “Clinical Impact of Routine Assessment of Patient-Reported Health Status in Heart Failure Clinic: The PRO-HF Trial”

Intraoperative Epoprostenol in Type II Heparin-Induced Thrombocytopenia During Left-Ventricular Assist Device Implantation: A Case Series and Review of Literature.

Type II heparin-induced thrombocytopenia and thrombosis (type II HITT) is a rare but serious complication in patients receiving heparin for anticoagulation. In type II HITT, an immune-mediated reaction against platelet factor four-heparin complexes results in thrombocytopenia and an elevated risk of thrombosis. This poses significant challenges for patients with advanced heart failure requiring urgent left-ventricular assist device (LVAD) implantation. The use of direct thrombin inhibitors, the typical alternative to heparin, is associated with increased bleeding risk and lacks a reversal agent, limiting their use in cardiac surgery. We present two cases of intraoperative epoprostenol to facilitate implantation of a durable LVAD in type II HITT, of which one case underwent preoperative plasmapheresis and intravenous immunoglobulin (IVIG) therapy. Epoprostenol, a prostacyclin analog, was used intraoperatively during LVAD implantation to inhibit platelet activation and allowed for the safe administration of heparin during cardiopulmonary bypass. Both patients underwent successful LVAD implantation without thrombotic or major bleeding complications. These cases highlight the potential of using intraoperative epoprostenol in conjunction with preoperative plasma exchange (PLEX) and IVIG to mitigate the risks associated with heparin use in patients with type II HITT, offering an alternative approach for this high-risk group requiring urgent cardiac surgery.

Proteomics in Acute Heart Transplant Rejection, On Behalf of the GRAfT Investigators.

Proteomic phenotyping can provide insights into rejection pathophysiology, novel biomarkers, and therapeutic targets. Within the prospective, multicenter Genomic Research Alliance for Transplantation study, 181 proteins were evaluated from blood drawn at the time of endomyocardial biopsy; protein fold change, logistic regression, and pathway analyses were conducted, with protein discovery adjusted for a 5% false discovery rate. Among 104 adult heart transplant patients (31% female sex, 53% Black race, median age 52 y), 74 had no rejection, 18 developed acute cellular rejection (ACR), and 12 developed antibody-mediated rejection (AMR). Differential expression was found in 2 proteins during ACR (inflammatory proteins CXCL10 and CD5) and 73 proteins during AMR. The most abundant AMR proteins were the heart failure biomarkers N-terminal pro-B-type natriuretic peptide and suppression of tumorigenicity 2. In univariate logistic regression, odds of identifying ACR on endomyocardial biopsy increased with doubling of CXCL10 (odds ratio [OR] 2.2 [95% confidence interval (CI), 1.3-3.6]) and CD5 (OR 4.7 [95% CI, 1.7-12.9]) concentrations, and odds of AMR increased with doubling of N-terminal pro-B-type natriuretic peptide (OR 13.0 [95% CI, 2.7-62.7) and suppression of tumorigenicity 2 (OR 4.8 [95% CI, 2.1-10.7]) concentrations. After multivariable analysis with clinical covariates, these proteins showed similar odds of ACR or AMR on biopsy. Pathway analysis identified T cell-receptor signaling and cell differentiation as key pathways in ACR and cardiovascular disease and cell turnover in AMR. Proteomic analysis reveals unique biomarkers and biological pathway expression in ACR and AMR. Cardiac injury-associated biomarkers were more pronounced in AMR, whereas inflammatory biomarkers were more pronounced in ACR. Proteomic analysis may provide insights into rejection pathophysiology, detection, and therapy.

Curricular Self-management for patients on ventricular assist device support decreases depression: A multicenter randomized controlled trial.

Utilization of ventricular assist device (VAD) support in patients with end-stage heart failure is well advanced. Recent studies emphasize the need to develop and evaluate evidence-based psychosocial support interventions for patients following VAD implantation. A national, multi-center study in four established German heart centers was initiated. An evidence-based VAD curriculum was developed; a randomized controlled trial evaluated the impact of the interprofessional intervention over time. Primary combined endpoint was the occurrence of adverse events (thromboembolic events, driveline infections, bleeding, rehospitalization, and death); secondary endpoints were psychosocial outcomes (anxiety, depression [HADS], quality of life [QoLVAD], social support [FSoZu], and self-management [SELMA]). A total of 140 patients were randomized block-wise to intervention (IG n = 70) or control (CG n = 70). Center-effects were considered. Instruments were completed at four time points (T0-T3). At baseline, intervention group (IG) patients were 19% female (control group [CG] 19%; p = 0.982); 58 ± 11 years. (CG 58 ± 11 years.; p = 0.966); 80% were implanted electively (CG 79%; p = 0.968). No significant difference in primary endpoint was found between IG versus CG (p > 0.05). For secondary endpoints, mixed linear regression revealed a significant reduction in depression scores in IG compared to CG (est. 1.18; 95% CI -2.17 to -0.18; p = 0.021). Clinically significant reductions in anxiety were greater in IG patients between T0 and T3 (IG 51.9%; CG 40.7%); increased anxiety was reported in 3.7% IG (11.1% CG). Mixed linear regression analyses favored IG (all >0.05) for QoL, social support, and self-management. A comprehensive curricular VAD intervention has potential to decrease depression levels and improve psychosocial outcomes of patients on VAD support.