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Left ventricular diastolic dysfunction (LVDD) has been reported to have strong correlation with exercise capacity. However, this relationship has not been studied extensively in community-dwelling older adults. Data on pulse and tissue Doppler echocardiographic estimates of resting early (E) and atrial (A) transmitral peak inflow and early (Em) mitral annular velocities, and six-minute walk test were obtained from 89 community-dwelling older adults (mean age, 74; range, 65-93 years; 54% women), without a history of heart failure. Overall, 47% had cardiovascular morbidity and 60% had normal diastolic function (E/A 0.75-1.5 and E:Em <10). Among the 36 individuals with LVDD, 83%, 14% and 3% had grade I (E/A <0.75, regardless of E/E(m)), II (E/A 0.75-1.5 and E/E(m) ≥10) and III (E/A>1.5 and E/E(m) ≥10) LVDD, respectively. Those with LVDD were older (77 versus 73 years; p = 0.001) and had a trend for higher prevalence of cardiovascular morbidity (58% versus 40%; p = 0.083). LVDD negatively correlated with six-minute walk distance (1013 versus 1128 feet; R = -0.25; p = 0.017). This association remained significant despite adjustment for cardiovascular morbidity (R = -0.35; p = 0.048), but lost significance when adjusted for age (R = -0.32; p = 0.105), age and cardiovascular morbidity (R = -0.38; p = 0.161), and additional adjustment for sex, race, body mass index, and systolic blood pressure (R = -0.44; p = 0.365). In conclusion, most community-dwelling older adults without heart failure had normal left ventricular diastolic function or grade-I LVDD. Although LVDD was associated with decreased performance on a six-minute walk test, that association was no longer evident after adjustment for age, body mass index and cardiovascular morbidity. [ABSTRACT FROM AUTHOR]

Background: Extracorporeal membrane oxygenation (ECMO) use in peripartum patients is rare, and there is a gap in the literature on the outcomes and guidance on using ECMO in peripartum patients. This study describes ECMO strategies our institution uses for peripartum patients and reports outcomes of ECMO use in peripartum patients with respiratory and/or cardiac failure., Methods: A case series of all peripartum patients, defined as pregnant or up to 6 weeks after delivery of an infant >20 weeks gestation, from 2018 to 2023 from a single center requiring ECMO support. Patients were included if ECMO was initiated in the setting of cardiac, pulmonary, or combined failure. Patient demographics, operative details, ECMO data, and adverse outcomes for maternal, fetus, and neonates were all collected., Results: Eighteen patients met the inclusion criteria. The cohort had a mean maternal age of 30.7 years old and was racially diverse. A majority of this cohort tested positive for COVID-19 ( n  = 10, 55%). ECMO was a bridge to recovery for all patients, of whom 14 (78%) were discharged out of the hospital alive. No patients received transplantation or a durable mechanical device. The most common complications were infection (25%) and postpartum hemorrhage (22%)., Conclusions: ECMO use in peripartum patients in a single tertiary center was associated with a high survival rate. Furthermore, a strong multidisciplinary team, careful reevaluation of clinical trajectory, and consideration of complications and risks associated with using ECMO in peripartum patients are possible frameworks to use when challenged with critically ill peripartum patients.

Background: Endomyocardial biopsy (EMB) is currently considered the gold standard for diagnosing cardiac allograft rejection. However, significant limitations related to histological interpretation variability are well-recognized. We sought to develop a methodology to evaluate EMB solely based on gene expression, without relying on histology interpretation., Methods: Sixty-four EMBs were obtained from 47 post-heart transplant recipients, who were evaluated for allograft rejection. EMBs were subjected to mRNA sequencing, in which an unsupervised classification algorithm was used to identify the molecular signatures that best classified the EMBs. Cytokine and natriuretic peptide peripheral blood profiling was also performed. Subsequently, we performed gene network analysis to identify the gene modules and gene ontology to understand their biological relevance. We correlated our findings with the unsupervised and histological classifications., Results: Our algorithm classifies EMBs into three categories based solely on clusters of gene expression: unsupervised classes 1, 2, and 3. Unsupervised and histological classifications were closely related, with stronger gene module-phenotype correlations for the unsupervised classes. Gene ontology enrichment analysis revealed processes impacting on the regulation of cardiac and mitochondrial function, immune response, and tissue injury response. Significant levels of cytokines and natriuretic peptides were detected following the unsupervised classification., Conclusion: We have developed an unsupervised algorithm that classifies EMBs into three distinct categories, without relying on histology interpretation. These categories were highly correlated with mitochondrial, immune, and tissue injury response. Significant cytokine and natriuretic peptide levels were detected within the unsupervised classification. If further validated, the unsupervised classification could offer a more objective EMB evaluation., (© 2023 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.)

Background: Extracorporeal membrane oxygenation (ECMO) has revolutionized the treatment of refractory cardiac and respiratory failure, and its use continues to increase, particularly in adults. However, ECMO-related morbidity and mortality remain high., Main Text: In this review, we investigate and expand upon the current state of the art in thoracic transplant and extracorporeal life support (ELS). In particular, we examine recent increase in incidence of heart transplant in patients supported by ECMO; the potential changes in patient care and selection for transplant in the years prior to updated United Network for Organ Sharing (UNOS) organ allocation guidelines versus those in the years following, particularly where these guidelines pertain to ECMO; and the newly revived practice of heart-lung block transplants (HLT) and the prevalence and utility of ECMO support in patients listed for HLT., Conclusions: Our findings highlight encouraging outcomes in patients bridged to transplant with ECMO, considerable changes in treatment surrounding the updated UNOS guidelines, and complex, diverse outcomes among different centers in their care for increasingly ill patients listed for thoracic transplant., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Palliative care trial recruitment of African Americans (AAs) is a formidable research challenge., Objectives: Examine AA clinical trial recruitment and enrollment in a palliative care randomized controlled trial (RCT) for heart failure (HF) patients and compare patient baseline characteristics to other HF palliative care RCTs., Methods: This is a descriptive analysis the ENABLE CHF-PC (Educate, Nurture, Advise, Before Life Ends: Comprehensive Heartcare for Patients and Caregivers) RCT using bivariate statistics to compare racial and patient characteristics and differences through recruitment stages. We then compared the baseline sample characteristics among three palliative HF trials., Results: Of 785 patients screened, 566 eligible patients with NYHA classification III-IV were approached; 461 were enrolled and 415 randomized (AA = 226). African Americans were more likely to consent than Caucasians (55%; P FDR = .001), were younger (62.7 + 8; P FDR = .03), had a lower ejection fraction (39.1 + 15.4; P FDR = .03), were more likely to be single ( P FDR = .001), and lack an advanced directive (16.4%; P FDR < .001). AAs reported higher goal setting (3.3 + 1.3; P FDR = .007), care coordination (2.8 + 1.3; P FDR = .001) and used more "denial" coping strategies (0.8 + 1; P FDR = .001). Compared to two recent HF RCTs, the ENABLE CHF-PC sample had a higher proportion of AAs and higher baseline KCCQ clinical summary scores., Conclusion: ENABLE CHF-PC has the highest reported recruitment rate and proportion of AAs in a palliative clinical trial to date. Community-based recruitment partnerships, recruiter training, ongoing communication with recruiters and clinician co-investigators, and recruiter racial concordance likely contributed to successful recruitment of AAs. These important insights provide guidance for design of future HF palliative RCTs., Trial Registration: ClinicalTrials.gov Identifier: NCT02505425.

Cardiac diseases are one of the most common causes of morbidity and mortality following liver transplantation (LT). Prior studies have shown that cardiac diseases affect close to one-third of liver transplant recipients (LTRs) long term and that their incidence has been on the rise. This rise is expected to continue as more patients with advanced age and/or non-alcoholic steatohepatitis undergo LT. In view of the increasing disease burden, a multidisciplinary initiative was developed to critically review the existing literature (between January 1, 1990 and March 17, 2021) surrounding epidemiology, risk assessment, and risk mitigation of coronary heart disease, arrhythmia, heart failure, and valvular heart disease and formulate practice-based recommendations accordingly. In this review, the expert panel emphasizes the importance of optimizing management of metabolic syndrome and its components in LTRs and highlights the cardioprotective potential for the newer diabetes medications (e.g., sodium glucose transporter-2 inhibitors) in this high-risk population. Tailoring the multidisciplinary management of cardiac diseases in LTRs to the cardiometabolic risk profile of the individual patient is critical. The review also outlines numerous knowledge gaps to pave the road for future research in this sphere with the ultimate goal of improving clinical outcomes., (Darshana M. Dadhania and Lisa B. VanWagner contributed equally.© 2022 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Ventriculo-arterial (VA) coupling has been shown to have physiologic importance in heart failure (HF). We hypothesized that the systemic arterial pulsatility index (SAPi), a measure that integrates pulse pressure and a proxy for left ventricular end-diastolic pressure, would be associated with adverse outcomes in advanced HF. We evaluated the SAPi ([systemic systolic blood pressure-systemic diastolic blood pressure]/pulmonary artery wedge pressure) obtained from the final hemodynamic measurement in patients randomized to therapy guided by a pulmonary arterial catheter (PAC) and with complete data in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial. Cox proportional hazards regression was performed for the outcomes of (a) death, transplant, left ventricular assist device (DTxLVAD) or hospitalization, (DTxLVADHF) and (b) DTxLVAD. Among 142 patients (mean age 56.8 ± 13.3 years, 30.3% female), the median SAPi was 2.57 (IQR 1.63-3.45). Increasing SAPi was associated with significant reductions in DTxLVAD (HR 0.60 per unit increase in SAPi, 95% CI 0.44-0.84) and DTxLVADHF (HR 0.81 per unit increase, 95% CI 0.70-0.95). Patients with a SAPi ≤ 2.57 had a marked increase in both outcomes, including more than twice the risk of DTxLVAD (HR 2.19, 95% CI 1.11-4.30) over 6 months. Among advanced heart failure patients with invasive hemodynamic monitoring in the ESCAPE trial, SAPi was strongly associated with adverse clinical outcomes. These findings support further investigation of the SAPi to guide treatment and prognosis in HF undergoing invasive hemodynamic monitoring., (© 2022. Springer Japan KK, part of Springer Nature.)

Context: Research priority guidelines highlight the need for examining the "dose" components of palliative care (PC) interventions, such as intervention adherence and completion rates, that contribute to optimal outcomes., Objectives: Examine the "dose" effect of PC intervention completion vs. noncompletion on quality of life (QoL) and healthcare use in patients with advanced heart failure (HF) over 32 weeks., Methods: Secondary analysis of the ENABLE CHF-PC intervention trial for patients with New York Heart Association (NYHA) Class III/IV HF. "Completers" defined as completing a single, in-person outpatient palliative care consultation (OPCC) plus 6 weekly, PC nurse coach-led telehealth sessions. "Non-completers" were defined as either not attending the OPCC or completing <6 telehealth sessions. Outcome variables were QoL and healthcare resource use (hospital days; emergency department visits). Mixed models were used to model dose effects for "completers" vs "noncompleters" over 32 weeks., Results: Of 208 intervention group participants, 81 (38.9%) were classified as "completers" with a mean age of 64.6 years; 72.8% were urban-dwelling; 92.5% had NYHA Class III HF. 'Completers' vs. "non-completers"" groups were well-balanced at baseline; however "noncompleters" did report higher anxiety (6.0 vs 7.0, P < 0.05, d = 0.28). Moderate, clinically significant, improved QoL differences were found at 16 weeks in "completers" vs. "non-completers" (between-group difference: -9.71 (3.18), d = 0.47, P = 0.002) but not healthcare use., Conclusion: Higher intervention completion rates of an early PC intervention was associated with QoL improvements in patients with advanced HF. Future work should focus on identifying the most efficacious "dose" of intervention components and increasing adherence to them., Trial Registration: ClinicalTrials.gov Identifier: NCT02505425., (Copyright © 2021 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Pulmonary artery proportional pulse pressure (PAPP) was recently shown to have prognostic value in heart failure (HF) with reduced ejection fraction (HFrEF) and pulmonary hypertension. We tested the hypothesis that PAPP would be predictive of adverse outcomes in patients with implantable pulmonary artery pressure monitor (CardioMEMS™ HF System, St. Jude Medical [now Abbott], Atlanta, GA, USA)., Methods: Survival analysis with Cox proportional hazards regression was used to evaluate all-cause deaths and HF hospitalisation (HFH) in CHAMPION trial 1 patients who received treatment with the CardioMEMS device based on the PAPP., Results: Among 550 randomised patients, 274 had PAPP ≤ the median value of 0.583 while 276 had PAPP>0.583. Patients with PAPP≤0.583 (versus PAPP>0.583) had an increased risk of HFH (HR 1.40, 95% CI 1.16-1.68, p=0.0004) and experienced a significant 46% reduction in annualised risk of death with CardioMEMS treatment (HR 0.54, 95% CI 0.31-0.92) during 2-3 years of follow-up. This survival benefit was attributable to the treatment benefit in patients with HFrEF and PAPP≤0.583 (HR 0.50, 95% CI 0.28-0.90, p<0.05). Patients with PAPP>0.583 or HF with preserved EF (HFpEF) had no significant survival benefit with treatment (p>0.05)., Conclusion: Lower PAPP in HFrEF patients with CardioMEMS constitutes a higher mortality risk status. More studies are needed to understand clinical applications of PAPP in implantable pulmonary artery pressure monitors., (Copyright © 2021 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Pregnancy after cardiac transplantation poses immense challenges. Maternal risks include hypertensive disorders of pregnancy, rejection, and failure of the cardiac allograft that may lead to death. Fetal risks include potential teratogenic effects of immunosuppression and prematurity. Because of the high-risk nature of pregnancy in a heart transplant patient, management of reproductive health after cardiac transplantation should include preconception counseling to all women in the reproductive age group before and after cardiac transplantation. Reliable contraception is vital as nearly half of the pregnancies in this population are unintended. Despite the associated risks, successful pregnancies after cardiac transplantation have been reported. A multidisciplinary approach proposed in this review is essential for successful outcomes. A checklist for providers to guide management is provided.

Altered inflammation and tissue remodeling are cardinal features of cardiovascular disease and cardiac transplant rejection. Neutrophils have increasingly been understood to play a critical role in acute rejection and early allograft failure; however, discrete mechanisms that drive this damage remain poorly understood. Herein, we demonstrate that early acute cardiac rejection increases allograft prolyl endopeptidase (PE) in association with de novo production of the neutrophil proinflammatory matrikine proline-glycine-proline (PGP). In a heterotopic murine heart transplant model, PGP production and PE activity were associated with early neutrophil allograft invasion and allograft failure. Pharmacologic inhibition of PE with Z-Pro-prolinal reduced PGP, attenuated early neutrophil graft invasion, and reduced proinflammatory cytokine expression. Importantly, these changes helped preserve allograft rejection-free survival and function. Notably, within 2 independent patient cohorts, both PGP and PE activity were increased among patients with biopsy-proven rejection. The observed induction of PE and matrikine generation provide a link between neutrophilic inflammation and cardiovascular injury, represent a potential target to reduce allogenic immune responses, and uncover a mechanism of cardiovascular disease that has been previously unrecognized to our knowledge.

Background: In 2016, the American Society of Echocardiography (ASE) released guidelines for identifying left ventricular (LV) diastolic dysfunction (DD), but its ability to detect early hemodynamic abnormalities is not well established, especially in the setting of subclinical coronary artery disease (CAD). We hypothesize that the accuracy of ASE categorization of early LVDD is affected by knowledge of whether CAD history is present., Methods: We studied 34 patients (age 62 ± 7 years) with NYHA class I to II symptoms and with transthoracic echocardiography without findings suggesting myocardial disease (all with preserved LV ejection fraction), who underwent cardiac catheterization with high-fidelity LV pressure measurement. Echocardiographic images were evaluated for LVDD using ASE algorithm without and with knowledge of CAD history and angiography findings. CAD was considered as having DD for the algorithm., Results: CAD was identified in 22 patients at catheterization (65%). Using ASE guidelines without including history of CAD or angiographic results, 29 patients were DD-, 3 were DD+ (all grade II), and 2 were indeterminate. Inclusion of CAD history recategorized 59% (n = 20) patients to DD+ (all grade I) from DD- (P < .0001). Nineteen of the recategorized patients (95%) had increased isovolumetric relaxation time (IVRT). The addition of echocardiographic IVRT improved discrimination between DD- and DD+, when the presence of CAD is unknown., Conclusions: 2016-ASE algorithm reasonably accurately identifies early LVDD at rest as reflected by LV catheterization when CAD is disclosed, but without knowledge of the presence of CAD, it underdiagnoses DD+ grade I. The addition of IVRT may improve early LVDD diagnostics., (© 2020 Wiley Periodicals LLC.)

Background: Mitochondrial dysfunction is associated with poor allograft prognosis. Mitochondrial-related gene expression (GE) in endomyocardial biopsies (EMBs) could be useful as a nonimmune functional marker of rejection. We hypothesize that acute cardiac allograft rejection is associated with decreased mitochondrial-related GE in EMBs., Methods: We collected 64 routines or clinically indicated EMB from 47 patients after heart transplant. The EMBs were subjected to mRNA sequencing. We conducted weighted gene coexpression network analysis to construct module-derived eigengenes. The modules were assessed by gene ontology enrichment and hub gene analysis. Modules were correlated with the EMBs following the International Society of Heart and Lung Transplantation histology-based criteria and a classification based on GE alone; we also correlated with clinical parameters., Results: The modules enriched with mitochondria-related and immune-response genes showed the strongest correlation to the clinical traits. Compared with the no-rejection samples, rejection samples had a decreased activity of mitochondrial-related genes and an increased activity of immune-response genes. Biologic processes and hub genes in the mitochondria-related modules were primarily involved with energy generation, substrate metabolism, and regulation of oxidative stress. Compared with International Society of Heart and Lung Transplantation criteria, GE-based classification had stronger correlation to the weighted gene coexpression network analysis-derived functional modules. The brain natriuretic peptide level, ImmuKnow, and Allomap scores had negative relationships with the expression of mitochondria-related modules and positive relationships with immune-response modules., Conclusions: During acute cardiac allograft rejection, there was a decreased activity of mitochondrial-related genes, related to an increased activity of immune-response genes, and depressed allograft function manifested by brain natriuretic peptide elevation. This suggests a rejection-associated mitochondrial impairment., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)