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Group B enteroviruses are known to cause fulminant myocarditis requiring heart transplantation. We present a case of recurrent enteroviral myocarditis post-transplant posing a diagnostic challenge. A 37-year-old male with a history of Diffuse large B-cell lymphoma (DLBCL) in remission for six years after chimeric antigen receptor T-cell therapy (CAR-T), underwent heart transplant for enteroviral myocarditis. He presented within 2 weeks with worsening left ventricular ejection fraction (LVEF). Cardiac MRI (CMR) demonstrated diffuse, patchy mid myocardial and subepicardial enhancement of multiple segments (Figure) with increased signal on T2 imaging suggestive of edema. Endomyocardial biopsy (EMB) showed mild cellular rejection (grade 1R) with negative C4 complement (C4d) without myocyte necrosis. He developed cardiogenic shock with a decline in his LVEF to 20% and required VA-ECMO support. A repeat EMB showed grade 0R with negative C4d staining. The molecular microscope diagnostic system was negative for B and T-cell-mediated rejection. He received plasma exchange therapy, intravenous immunoglobulin (IVIG), and thymoglobulin. Lymphocyte counts performed on admission showed an absolute count of 31 for CD3 (normal-427 cell/mm3) and no detectable CD19 cells suggesting severe combined immune deficiency. EMB was positive for enterovirus by reverse transcriptase polymerase chain reaction (RT-PCR) thus diagnosing recurrent enteroviral myocarditis. After an extended course of Intravenous Immune globulin (IVIG), he had clinical recovery with an improvement of his LVEF to 55%. This is the first case in literature that highlights recurrence of biopsy-negative enteroviral myocarditis post-transplant, particularly with persistent B cell depletion from past exposure to anti-CD19 CAR-T cell therapy. We hypothesize that the severity of his presentation post-transplant was due to this unforeseen combined immune deficiency in addition to intensive immunosuppression. [ABSTRACT FROM AUTHOR]

Cardiac allograft rejection (AR) diagnosis has historically relied on endomyocardial biopsy (EMBx) and histopathology (HP). Quantifying donor-derived cell free DNA (ddcfDNA) has recently offered a non-invasive alternative for detecting graft injury. EMBx mRNA analysis via the molecular microscope profiles (MMP) quantifies AR probability not subject to HP interpretation. Our aim was to evaluate the clinical role of MMP in cardiac transplant recipients (HTx) with positive ddcfDNA. We identified 39 patients with ddcfDNA testing and subsequent EMBx for HP (n=36) and MMP (n=39) analysis. MMP was conducted by the molecular microscope diagnostic system (MMDX™). Patients with multi-organ transplantation or coronary allograft vasculopathy were excluded. MMP, HP, echo and ddcfDNA association were assessed using logistical regression (SPSS™). Average time post-transplant was 1585 ±1435 days, average LVEF 55%, and average ddcfDNA 0.81 ± 1.1. Donor specific antibodies were present in 14/39 of patients. MMP was abnormal in 18/39 patients and correlated with ddcfDNA levels (p=0.007) and HP (p=0.05), but not with LVEF (p=0.71). MMP abnormalities included 9 antibody mediated rejection (AMR), 5 acute cellular rejection (ACR), and 4 injury patterns. By HP, biopsies were abnormal in 18/36 patients: 18 ACR (grade 1) and 1 AMR (grade 2). Abnormal HP did not correlate with ddcfDNA levels (p= 0.07). HP and MMP are often discordant, Table 1. Abnormal MMP correlated with both ddcfDNA and HP, but not with LVEF. Large prospective clinical trials are needed to define clinical outcomes from treatment strategies based on biopsy results. Multi-modality testing may be necessary to monitor cardiac transplant patients for rejection and avoid misclassification. [ABSTRACT FROM AUTHOR]

While there has been a decline in the use of digoxin in patients with heart failure and atrial fibrillation, acute and chronic digoxin toxicity remains a significant clinical problem. Digoxin's narrow therapeutic window and nonspecific signs and symptoms of toxicity create clinical challenges and uncertainty around the diagnostic criteria of toxicity and responsive treatment choices for the bedside clinician. A systematic review of published literature on digoxin toxicity (34,587 publications over 6 decades, with 114 meeting inclusion criteria) was performed to develop 33 consensus statements on diagnostic and therapeutic approaches which were then evaluated through a modified Delphi process involving a panel of experts in cardiology, nursing, emergency medicine, and medical toxicology. The results demonstrate agreement about the need to consider time of ingestion and nature of the exposure (ie, acute, acute-on-chronic, chronic) and the use of digoxin immune Fab for life-threatening exposure to decrease risk of death. While several areas of continued uncertainty were identified, this work offers formalized guidance that may help providers better manage this persistent clinical challenge., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Macitentan is a dual endothelin receptor antagonist (ERA) approved for treating pulmonary arterial hypertension (PAH). SOPRANO evaluated the efficacy and safety of macitentan versus placebo in pulmonary hypertension (PH) patients after left ventricular assist device (LVAD) implantation. SOPRANO was a phase 2, multicenter, double-blind, randomized, placebo-controlled, parallel-group study. Patients with an LVAD implanted within the prior 90 days who had persistent PH (i.e., mean pulmonary arterial pressure ≥25 mmHg, pulmonary artery wedge pressure [PAWP] ≤18 mmHg, and pulmonary vascular resistance [PVR] >3 Wood units [WU]) were randomized (1:1) to macitentan 10 mg or placebo once daily for 12 weeks. The primary endpoint was change in PVR. Secondary endpoints included change in right-heart catheterization hemodynamic variables, N-terminal prohormone of brain natriuretic peptide levels, World Health Organization functional class, and safety/tolerability. Fifty-seven patients were randomized to macitentan ( n  = 28) or placebo ( n  = 29). A statistically significant reduction in PVR from baseline to Week 12 was observed with macitentan versus placebo (placebo-corrected geometric mean ratio, 0.74; 95% confidence interval, 0.58-0.94; p  = .0158). No statistically significant differences were observed in secondary endpoints. In a post-hoc analysis, 66.7% of patients receiving macitentan achieved PVR <3 WU versus 40.0% receiving placebo ( p  = .0383). Macitentan was generally well tolerated; adverse events were consistent with those in previous PAH studies with macitentan. In conclusion, macitentan showed promising tolerability and significantly reduced PVR in PH patients with persistently elevated PVR after LVAD implantation. ClinicalTrials. gov identifier: NCT02554903., Competing Interests: Robert P. Frantz is receiving grants and research support from United Therapeutics, Medtronic, and Gossamer Bio, and is scientific medical advisor to Altavant, ShouTi, Liquidia Corporation, Merck, Tenax Therapeutics, and Janssen Pharmaceutical Companies of Johnson & Johnson. His institution has received funding from Bayer and Gossamer Bio. Shashank S. Desai has served on the speakers’ bureau for Abbott. Gregory Ewald is on the speakers’ bureau and is a consultant with Abbott. Veronica Franco's institution receives research support from Acceleron/Merck, Gossamer, Janssen, United Therapeutics, Aerovate Therapeutics, Respira, and Cereno Scientific. Antoine Hage is receiving grants and research support from United Therapeutics, Lung LLC, Arena, Reata, and Bayer, and is a stockholder in Johnson & Johnson and Pfizer. Evelyn M. Horn's institution has received funding from Gossamer, Acceleron/Merck, Abbott, and Cereno Scientific. Stacy Mandras is a speaker and consultant for United Therapeutics and Bayer Pharmaceuticals. Myung H. Park is a scientific medical advisor with AstraZeneca. Ashwin K. Ravichandran is consulting/speaking for Abbott, Medtronic and speaking for United Therapeutics, Janssen, and Bayer; he personally receives no grants from these companies, but his institution does. Ronald Zolty is a consultant for Janssen Pharmaceutical Companies of Johnson & Johnson, Bayer, United Therapeutics, and Alnylam. Mark A. Rocco, Mona Selej, and Carol Zhao were employees of Actelion Pharmaceuticals US, Inc., South San Francisco, CA (at the time of manuscript development) and are current stockholders of Johnson & Johnson. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 Actelion Pharmaceuticals US, Inc. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Background: Preoperative amiodarone effects on postorthotopic heart transplant (OHT) outcomes remain controversial., Objective: The purpose of this study was to determine the effect of cumulative pre-OHT amiodarone exposure on severe primary graft dysfunction (PGD)., Methods: We retrospectively reviewed adult OHT recipients between August 2012 and June 2018. Primary outcome was severe PGD in patients receiving amiodarone at 3, 6, and 12 months prior to OHT compared with those not receiving amiodarone. Secondary outcomes included intensive care unit (ICU) and hospital length of stay, duration of mechanical ventilation, early graft failure (EGF), mortality at 3, 6, and 12 months post-OHT, and 30-day incidence of postoperative tachyarrhythmias, bradycardia, permanent pacemaker implantation, and rejection., Results: Incidence of severe PGD was 12.5% in those who received amiodarone compared to 6.8% in those who did not (14 vs 6, P = 0.18). Cumulative preoperative amiodarone significantly increased the odds of severe PGD at 3 months (odds ratio [OR]: 1.03; 95% confidence interval [CI]: 1.001-1.06; P = 0.044) and 6 months (OR: 1.02, 95% CI: 1.003-1.044; P = 0.024) in a multivariate logistic regression. Patients on amiodarone had significantly higher rates of postoperative bradycardia (13.4% vs 4.5%, P = 0.03)., Conclusion and Relevance: A trend toward increased PGD was present in patients receiving preoperative amiodarone. This finding combined with the regression showing significantly increased odds of PGD with increasing 3 and 6 month cumulative amiodarone dose is clinically concerning. Escalation of care with pacemaker implantation was required more frequently in patients on pre-OHT amiodarone., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: The primary goal of this study was to identify and understand the burden experienced by informal caregivers of patients with HF at the time of hospital discharge. The researchers aimed to guide future education interventions and promote informal caregiver burden screening., Design: The researchers administered the Zarit Burden Interview (ZBI) as a quantitative tool to assess informal caregiver burden. The ZBI is a standardized questionnaire used to measure the extent of burden experienced by informal caregivers. After administering the ZBI, the researchers conducted semi-structured interviews with five informal caregivers of patients with HF. These interviews were guided by probing questions related to ZBI items that were rated with high levels of burden (3 "quite frequently" or 4 "nearly always")., Results: The quantitative data showed that the informal caregivers' burden scores on the ZBI ranged from 4 to 41. Male informal caregivers tended to report lower burden scores. The non-spouse informal caregiver had the highest burden score at 41. The qualitative analysis of the interviews revealed several themes related to informal caregiver burden, including fear, patient expectations, patient dependence on caregivers, social isolation, and stressors associated with medication changes after discharge. Despite the qualitative insights into specific burden-related issues, the quantitative analysis of the ZBI scores showed that, on average, informal caregivers reported little to no burden at the time of acute exacerbation of HF in the patient., Conclusion: The study's findings suggest that while informal caregivers may not report prominent levels of overall burden, they do face specific challenges and stressors, such as social isolation and managing medication changes post-discharge. These findings can inform the development of targeted support and interventions for informal caregivers of patients with HF., Competing Interests: Declaration of competing interest All authors confirm there is zero conflict of interest for this manuscript., (Published by Elsevier Inc.)

Background: Heart failure with preserved ejection fraction (HFpEF) is common in type 2 diabetes mellitus (T2D), leading to high morbidity and mortality. Managing HFpEF in diabetic patients is challenging with limited treatments. Sodium-glucose co-transporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP1-RA) have shown potential cardiovascular benefits. This meta-analysis compares the effects of GLP1-RA and SGLT2 inhibitors on HFpEF in T2D patients., Methods: We conducted a meta-analysis of randomized controlled trials (RCTs) and observational studies evaluating GLP1-RA and SGLT2 inhibitors' impact on HFpEF in T2D patients. Databases searched included PubMed, MEDLINE, and Cochrane Library up to July 2024. Primary outcomes were changes in left ventricular ejection fraction (LVEF), myocardial fibrosis (extracellular volume fraction, ECV), and functional capacity (6-minute walk test, 6MWT). Secondary outcomes included HbA1c, body weight, and systolic blood pressure (SBP).  RESULTS: Twelve studies with 3,428 patients (GLP1-RA: 1,654; SGLT2 inhibitors: 1,774) were included. Both GLP1-RA and SGLT2 inhibitors significantly improved LVEF compared to placebo (GLP1-RA: mean difference [MD] 2.8%, 95% confidence interval [CI] 1.5 to 4.1, p < 0.001; SGLT2 inhibitors: MD 3.2%, 95% CI 2.0 to 4.4, p < 0.001). SGLT2 inhibitors significantly reduced myocardial fibrosis (MD -3.5%, 95% CI -4.2 to -2.8, p < 0.001) more than GLP1-RA (MD -2.3%, 95% CI -3.0 to -1.6, p < 0.001). Functional capacity improved significantly with both treatments (GLP1-RA: MD 45 m, 95% CI 30 to 60, p < 0.001; SGLT2 inhibitors: MD 50 m, 95% CI 35 to 65, p < 0.001). Secondary outcomes showed reductions in HbA1c (GLP1-RA: MD -1.1%, 95% CI -1.4 to -0.8, p < 0.001; SGLT2 inhibitors: MD -1.0%, 95% CI -1.3 to -0.7, p < 0.001) and body weight (GLP1-RA: MD -2.5 kg, 95% CI -3.1 to -1.9, p < 0.001; SGLT2 inhibitors: MD -2.0 kg, 95% CI -2.6 to -1.4, p < 0.001). Both treatments significantly lowered SBP (GLP1-RA: MD -5.2 mmHg, 95% CI -6.5 to -3.9, p < 0.001; SGLT2 inhibitors: MD -4.8 mmHg, 95% CI -6.0 to -3.6, p < 0.001)., Conclusions: GLP1-RA and SGLT2 inhibitors significantly benefit HFpEF management in T2D patients. SGLT2 inhibitors reduce myocardial fibrosis more effectively, while both improve LVEF, functional capacity, and metabolic parameters. These therapies should be integral to HFpEF management in diabetic patients. Further research is needed on long-term outcomes and potential combined therapy effects., (© 2024. The Author(s).)

Background : This study explores heart failure (HF) dyadic contextual factors and caregiver burden during acute exacerbation hospitalization and discharge. Methods : It employed a mixed-methods approach, with HF dyads completing questionnaires and semi-structured interviews at a one-week post-discharge outpatient visit. Quantitative tools included the SF-12 Quality of Life, Zarit Burden Interview (ZBI), Bakas Caregiving Outcomes Scale (BCOS), and Self-Care of Heart Failure Index v. 6 (SCHFI). Thematic analysis was conducted on interview data to assess caregiver burden, disease trajectory, comorbidities, caregiving time, and employment status. Results : Twelve HF dyads participated, with caregivers (six female, six male) averaging 65.76 years. The ZBI indicated a low caregiver burden (median score of 15), but qualitative data revealed a higher perceived burden related to social isolation, future fears, and caregiver dependence. Male caregivers reported a lower burden than females. Positive goal congruence was noted in caregiving hours and HF management compliance. HF patients had a 10-year survival prediction of 22.75% per the Charlson Comorbidity Index, with 69% in NYHA class III and an average ejection fraction of 37.7%. Caregivers working full-time and caring for higher NYHA-class patients showed higher ZBI and BCOS scores. Conclusions : The study highlights the need for mixed methods and longitudinal research to understand HF disease trajectory and caregiver burden, emphasizing the importance of including caregivers in HF education and screening for perceived burden to improve outcomes and reduce re-hospitalizations.

Aim: The six-minute walk test (6MWT) is a common measure of functional capacity in patients with heart failure (HF). Primary clinical study end points in cardiomyopathy (CM) trials, including transthyretin-mediated amyloidosis with CM (ATTR-CM), are often limited to hospitalization and mortality. Objective: To investigate the relationship between the 6MWT and hospitalization or mortality in CM, including ATTR-CM. Method: A PRISMA-guided systematic literature review was conducted using search terms for CM, 6MWT, hospitalization and mortality. Results: Forty-one studies were identified that reported 6MWT data and hospitalization or mortality data for patients with CM. The data suggest that a greater 6MWT distance is associated with a reduced risk of hospitalization or mortality in CM. Conclusion: The 6MWT is an accepted alternative end point in CM trials, including ATTR-CM.

Rationale: Oral treprostinil slows disease progression and improves exercise capacity in pulmonary arterial hypertension; however, titration can be prolonged. Published data suggests prostacyclin-naïve patients achieve total daily oral treprostinil doses of about 6 mg by Week 16, while those on prior parenteral treprostinil reach higher doses at the same timepoint., Objectives: EXPEDITE (NCT03497689), a single-arm, multicenter study, assessed the efficacy of rapid parenteral treprostinil induction to quickly reach higher doses of oral treprostinil for the treatment of pulmonary arterial hypertension., Methods: Parenteral treprostinil was titrated for 2-8 weeks, followed by cross-titration of oral treprostinil. The primary endpoint was percentage of patients reaching ≥12 mg daily of oral treprostinil at Week 16. Secondary endpoints included clinical changes from baseline to Week 16., Results: Twenty-nine prostacyclin-naïve patients were included in efficacy analyses. At Week 16, the mean daily oral treprostinil dose was 16.4 mg; 79% of patients met the primary endpoint. From baseline to Week 16, median REVEAL Lite 2 score improved (decreased) from 6 to 3.5 (p = 0.0006). Statistically significant improvements were also seen in World Health Organization Functional Class, N-terminal-pro brain natriuretic peptide levels, 6-minute walk distance, right atrial area, Borg Dyspnea Score, and emPHasis-10 score. Favorable trends were seen in risk stratification, echocardiography parameters, disease symptoms, and treatment satisfaction., Conclusion: Short-course parenteral treprostinil induction resulted in oral treprostinil doses over twice those reported in de novo initiations and may be a useful approach to quickly achieve the therapeutic benefits of oral treprostinil., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: CEM – United Therapeutics Corporation (research, consulting, speakers bureau, advisory board), Janssen (research, speakers bureau, advisory board), Insmed (research), Bayer (advisory board, steering committee); VF – United Therapeutics Corporation (research), Merck (research), Acceleron (research), Johnson & Johnson (research), Respira (research), Aerovate (research), Cereno (research), Abbott (research); JSS – United Therapeutics Corporation (research, speakers bureau), Bayer (research, speakers bureau); VB – United Therapeutics Corporation (consulting); JK – United Therapeutics Corporation (research, consulting, speakers bureau, advisory board), Janssen (research, consulting, speakers bureau, advisory board), Acceleron (research), Gossamer (research), Bayer (consulting, speakers bureau, advisory board); RZ – United Therapeutics Corporation (consulting), Bayer (consulting), Janssen (consulting), Johnson & Johnson (consulting); LMG – United Therapeutics Corporation (research, consulting, advisory board), Janssen (research, consulting), Gossamer bio (research, consulting), Merch (research, consulting), Bayer (research, consulting); JH – Acceleron (research), CardiolRx (research), Aaadi Bioscience (research), Astra Zeneca (spouse); JME – United Therapeutics Corporation (research, consulting), Janssen (research), Liquidia (research, consulting), Phase Bio (research), Gossamer Bio (research, consulting), Bayer (research, consulting), Acceleron (research), Altavant (research, consulting), Aerovate (research consulting), Tenax (research), Pharmosa (research), Merck (consulting); AR – United Therapeutics Corporation (consulting), Bayer (consulting), Actelion (consulting); DC, ES, SS, CMT, MB – United Therapeutics Corporation (employee); RJO – United Therapeutics Corporation (research, consulting), Janssen (research, consulting), Merck (research, consulting), Gossamer Bio (research), Insmed (research)., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Treprostinil is a prostacyclin analogue that targets multiple cellular receptors to treat pulmonary arterial hypertension (PAH). In certain scenarios, patients may require aggressive treprostinil titration. Several studies have demonstrated that higher doses of treprostinil lead to greater clinical benefit. Data supports successful transitions from parenteral to oral treprostinil; however, administration routes, transition duration, and transition setting vary in the real-world. The EXPEDITE clinical trial (NCT03497689) prospectively studied whether rapid parenteral treprostinil induction can be used to achieve high doses of oral treprostinil (total daily dose: ≥12 mg) in prostacyclin naïve PAH patients. Parenteral prostacyclin induction may be more appropriate for patients who need to reach therapeutic dosing more urgently than longer titration durations reported with conventional de novo oral treprostinil initiation. This summary provides strategies utilized in EXPEDITE. Parenteral treprostinil was initiated at 2 ng/kg/min intravenously or subcutaneously; clinicians determined the frequency and dose increment of up-titration. Two distinct transition schedules from parenteral to oral treprostinil were employed: rapid cross-titration in an inpatient setting (median: 2 days) or gradual cross-titration in an outpatient setting (median: 5 days). Patient status was closely monitored after transition; oral treprostinil dose was titrated to clinical effect and tolerability. Factors considered when individualizing dosing strategies included parenteral and oral treprostinil target doses, nursing support, patient education, medication counseling and adverse events management. EXPEDITE demonstrated the time to a therapeutic dose of oral treprostinil is significantly shorter when utilizing a short-term parenteral induction strategy and may be suitable for patients requiring aggressive titration of oral treprostinil., Competing Interests: J. F. Kingrey is part of the speaker bureau for United Therapeutics, Bayer pharmaceuticals, and Janssen Pharmaceuticals, attends advisory boards for United Therapeutics, Bayer, and Janssen, consults for United Therapeutics, Bayer, Janssen, and conducts research for United Therapeutics, Janssen, Acceleron, Gossamer Bio. C. E. Miller is part of the speaker bureau for United Therapeutics, Janssen, and Bayer, attends advisory boards for United Therapeutics and Janssen, consults for United Therapeutics, and conducts clinical research for United Therapeutics, Janssen, Bayer, and Insmed. J. S. Smith serves as a speaker for and has received research funds from Bayer and United Therapeutics. V. Franco has served on advisory boards for United Therapeutics and has supported research for United Therapeutics, Merck, Acceleron, Johnson and Johnson, Respira, Aerovate, Cereno, and Abbott. R. Zolty has received payments for consulting on behalf of United Therapeutics, Bayer, and Janssen/Johnson and Johnson. R. J. Oudiz has received grants from Acceleron/Merck, Gossamer Bio, Insmed, Janssen, and United Therapeutics and honoraria/speaker fees from Merck, Janssen, and United Therapeutics. J. M. Elwing consults for United Therapeutics, Altavant, Aerovate, Bayer, Gossamer Bio, Liquida, and Merck and has received research support and grants from Janssen, United Therapeutics, Liquidia, Phase Bio, Gossamer Bio, Bayer, Acceleron, Altavant, Aerovate, Tenax, and Pharmosa. J. H. Huston has conducted clinical trials for Acceleron, CardiolRx, and Aadi Bioscience. L. Melendres‐Groves has received honoraria and/or fees for consultancy and advisory committees for United Therapeutics Corporation outside of submitted works. A. Ravichandran reports personal fees from United Therapeutics, Bayer, and Actelion outside the submitted work. V. Balasubramanian serves as a consultant for United Therapeutics. B. Wu, S. Hwang, S. Seaman, and M. Broderick are paid employees of United Therapeutics. F. F. Rahaghi has consulted for United Therapeutics, Janssen PH, Merck, and Altavant; served as a speaker for United Therapeutics, Janssen PH, and Bayer; and received research funding from Janssen, Bayer, Merck, Gossamer, and Bellerophon., (© 2023 The Authors. Pulmonary Circulation published by Wiley Periodicals LLC on behalf of the Pulmonary Vascular Research Institute.)

Background: Heart failure is a major health problem with significant economic burden in the United States. Educating heart failure dyads (heart failure patient and informal caregiver) is a relatively new domain and is being proposed by providers, policy makers, and third-party payors. Nurse-led dyad education can improve quality of life and reduce hospital admissions in the heart failure population., Objectives: This integrative literature review focused on evaluating design, delivery content, and outcomes of nurse-led dyadic educational interventions., Methods: PubMed, CINAHL, Cochrane, and Google Scholar databases (1999 -2022) were searched for quantitative and qualitative studies that included these search terms: heart failure, dyads, nonmedical caregivers, caregivers, randomized controlled trials, nurse-led education, education., Results: The search yielded 92 articles. The results included seven randomized controlled trials and one pilot study conducted from 2005 to 2017. Sample sizes ranged from 20 to 155 dyads. Dyads who received education interventions had positive outcomes. Face-to-face coaching provided stronger outcomes. Interventions varied in length from baseline to three months, with post-intervention follow-ups from one to 12 months., Conclusions: A paucity of studies of nurse-led heart failure dyadic educational interventions have been reported in the literature. To advance the science and decrease heart failure readmissions, greater efforts to study and incorporate education and support for heart failure dyads is needed, along with assessment of both patient and caregiver outcomes., Competing Interests: Conflict of Interest Authors do not have a conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Distal pulmonary arterial remodeling and elevated pulmonary vascular resistance are characteristic of pulmonary arterial hypertension (PAH). Current approved vasodilator-specific PAH therapy that includes phosphodiesterase-5 inhibitors, soluble guanylate cyclase stimulators, endothelin receptor antagonists, and prostanoids has demonstrated dramatic enhancement in functional capacity, quality of life, and invasive hemodynamics. However, none of these treatments are curative, underscoring the need to identify new pathophysiologic signaling pathways., Areas Covered: The author provides a comprehensive review on current knowledge and recent development in the understanding of PAH. Furthermore, the author discusses PAH potential genetic causes as well as novel molecular signaling pathways. This article also reviews the currently approved PAH specific therapy based on pivotal clinical trials and ongoing clinical trials using novel compounds that specifically target PAH pathogenesis., Expert Opinion: The discovery of novel signaling pathways - growth factors, tyrosine kinases, BMPs, estrogen, and serotonin - involved in the PAH pathobiology will lead within the next 5 years to the approval of new therapeutic agents targeting these different pathways. If proven beneficial, these new agents may reverse or at least prevent the progression of this devastating and lethal disease.

Introduction: We aimed to assess the impact of digoxin use following left ventricular assist device (LVAD) implantation on clinical outcomes., Methods: Patients implanted with continuous flow LVADs at a single academic medical center and survived to initial hospital discharge were included in the analysis ( n  = 346). Clinical events were captured at a maximum of 2 years of follow up. Digoxin use was defined as 30-day continuous use post-LVAD. Negative binomial regression and Kaplan-Meier method were used to assess the association between digoxin use and clinical outcomes., Results: Mean age of the cohort was 56 years (±13) and 23% (79/346) were female sex. Digoxin was used in 144 patients (41.6%) for a median of 268 days (IQR 154, 616). Digoxin use was associated with a significant reduction in cumulative incidence of gastrointestinal bleeding (GIB) (15% vs 26%, p  = 0.004). After adjusting for age, hypertension, post-operative hemoglobin, RDW, potassium, and GFR, and use of angiotensin receptor/neprilysin inhibitor, there remained a significant 47% reduction in GIB incidence in patients treated with digoxin. There was no significant difference in cumulative incidence in right ventricular failure (RVF) between the two groups. There was no difference in overall 2-year survival between groups., Conclusions: Digoxin use was associated with reduction in GIB events, but not in RVF or mortality. Further studies are needed to confirm these findings and to investigate optimal timing and patient population.