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Hereditary transthyretin amyloidosis (hATTR) is an autosomal dominant, adult-onset disease that stems from point mutations in the TTR gene encoding the protein transthyretin. The disease is progressive and life-threatening and is associated with amyloid deposits in multiple organs including the heart, kidney, skin, eyes, nervous system, and gastrointestinal tract. Genotypic and phenotypic heterogeneity is a characteristic hallmark of hereditary transthyretin amyloidosis. Herein, we present a rare variant of hATTR cardiomyopathy secondary to Ser97Tyr mutation, having been documented only in a handful of families previously. This case serves as a valuable opportunity to elucidate the clinico-pathogenesis of this disease, highlight the aggressive nature of this genetic mutation (c.290C>A; p.Ser97Tyr), and document the response to the latest advances in treatment currently available., Competing Interests: Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Yarrarapu et al.)

Background: Severe primary graft dysfunction (PGD) is a major cause of early mortality after heart transplant, but the impact of donor organ preservation conditions on severity of PGD and survival has not been well characterized., Methods: Data from US adult heart-transplant recipients in the Global Utilization and Registry Database for Improved Heart Preservation-Heart Registry (NCT04141605) were analyzed to quantify PGD severity, mortality, and associated risk factors. The independent contributions of organ preservation method (traditional ice storage vs controlled hypothermic preservation) and ischemic time were analyzed using propensity matching and logistic regression., Results: Among 1,061 US adult heart transplants performed between October 2015 and December 2022, controlled hypothermic preservation was associated with a significant reduction in the incidence of severe PGD compared to ice (6.6% [37/559] vs 10.4% [47/452], p = 0.039). Following propensity matching, severe PGD was reduced by 50% (6.0% [17/281] vs 12.1% [34/281], respectively; p = 0.018). The Kaplan-Meier terminal probability of 1-year mortality was 4.2% for recipients without PGD, 7.2% for mild or moderate PGD, and 32.1%, for severe PGD (p < 0.001). The probability of severe PGD increased for both cohorts with longer ischemic time, but donor hearts stored on ice were more likely to develop severe PGD at all ischemic times compared to controlled hypothermic preservation., Conclusions: Severe PGD is the deadliest complication of heart transplantation and is associated with a 7.8-fold increase in probability of 1-year mortality. Controlled hypothermic preservation significantly attenuates the risk of severe PGD and is a simple yet highly effective tool for mitigating post-transplant morbidity., (Copyright © 2024 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Data on long term outcomes in heart transplant recipients from Coronavirus disease 2019 (COVID-19) positive donors are limited., Methods and Results: We present a series of nine patients who underwent heart transplants from COVID-19 PCR-positive donors between November 2021 to August 2022 with mean follow-up of 12.12 ± 3 months. All the recipients received two doses of COVID-19 vaccine and had at least 6 months follow-up. Eight recipients had acceptable long-term outcomes; one patient died during index admission from primary graft dysfunction. Details regarding donor and recipient characteristics, management and outcomes are provided. Two patients developed deep vein thrombosis, and one patient underwent pacemaker implantation for sinus node dysfunction. Among the surviving eight patients, none developed COVID-19 infection during follow-up period. There was no significant difference in outcome parameters when compared to patients who received hearts from donors who tested negative for COVID-19 during the same time period at our center., Conclusion: Keeping in mind the significant waitlist mortality in patients awaiting heart transplantation, COVID-19-positive donors should be considered for heart transplantation to help expand the donor pool and potentially reduce waitlist mortality., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Recent studies indicate that donor innate immune responses participate in initiating and accelerating innate responses and allorecognition in the recipient. These immune responses negatively affect recipient outcomes and predispose recipients to cardiovascular death (CV death). We hypothesized that a donor cause of death (COD) associated with higher levels of innate immune response would predispose recipients to more adverse outcomes post-transplant, including CV death., Methods: We performed a single-institution retrospective analysis comparing donor characteristics and COD to recipient adverse cardiovascular outcomes. We analyzed the medical records of local adult donors (age 18-64) in a database of donors where adequate data was available. Donor age was available on 706 donors; donor sex was available on 730 donors. We linked donor characteristics (age and sex) and COD to recipient CV death. The data were analyzed using logistic regression, the log-rank test of differences, and Tukey contrast., Results: Donor age, female sex, and COD of intracranial hemorrhage were significantly associated with a higher incidence of recipient CV death., Conclusions: In this single institution study, we found that recipients with hearts from donors over 40 years, donors who were female, or donors who died with a COD of intracranial hemorrhage had a higher frequency of CV death. Donor monitoring and potential treatment of innate immune activation may decrease subsequent recipient innate responses and allorecognition stimulated by donor-derived inflammatory signaling, which leads to adverse outcomes.

Background: There is a paucity of data regarding epidemiology, temporal trends, and outcomes of patients with cardiogenic shock (CS) and end-stage renal disease (chronic kidney disease stage V on hemodialysis)., Methods: This is a retrospective cohort study using the United States Renal Data System database from January 1, 2006 to December 31, 2019. We analyzed trends of CS, percutaneous mechanical support (intraaortic balloon pump, percutaneous ventricular assist device [Impella and Tandemheart], and extracorporeal membrane oxygenation) utilization, index mortality, 30-day mortality, and 1-year all-cause mortality in end-stage renal disease patients., Results: A total of 43 825 end-stage renal disease patients were hospitalized with CS (median age, 67.8 years [IQR, 59.4-75.8] and 59.1% men). From 2006 to 2019, the incidence of CS increased from 275 to 578 per 100 000 patients ( P trend <0.001). The index mortality rate declined from 54.1% in 2006 to 40.8% in 2019 ( P trend =0.44), and the 1-year all-cause mortality decreased from 63% in 2006 to 61.8% in 2018 ( P trend =0.73), but neither trend was statistically significant. There was a significantly decreased utilization of intra-aortic balloon pumps from 17 832 to 7992 ( P trend <0.001), increased utilization of percutaneous ventricular assist device from 137 to 5201 ( P trend <0.001) and increase in extracorporeal membrane oxygenation use from 69 to 904 per 100 000 patients ( P trend <0.001). After adjusting for covariates, there was no significant difference in index mortality between CS patients requiring percutaneous mechanical support versus those not requiring percutaneous mechanical support (odds ratio, 0.97 [CI, 0.91-1.02]; P =0.22). On multivariable regression analysis, older age, peripheral vascular disease, diabetes, and time on dialysis were independent predictors of higher index mortality., Conclusions: The incidence of CS in end-stage renal disease patients has doubled without significant change in the trend of index mortality despite the use of percutaneous mechanical support., Competing Interests: Disclosures None.

Competing Interests: Conflict of interest: All authors have no conflicts of interest to disclose.

There is a paucity of data regarding the impact of liver fibrosis on patients with stage D heart failure (HF). We conducted a retrospective study (January 1, 2017 to December 12, 2020) in patients with stage D HF who underwent liver biopsy as part of their advanced HF therapy evaluation. Baseline characteristics and 1-year outcomes were compared between no- or mild-to-moderate-fibrosis (grade 0 to 2) and advanced-fibrosis (grade 3 to 4) groups. Of 519 patients with stage D HF, 136 who underwent liver biopsy (113 [83%] no or mild-to-moderate fibrosis and 23 [17%] advanced fibrosis) were included. A total of 71 patients (52%) received advanced HF therapies (23 heart transplantation, 48 left ventricular assist devices). One-year mortality was higher among patients with advanced fibrosis (52% vs 18%, p <0.001). Further subgroup analysis suggested a trend toward increased 1-year mortality among patients with advanced fibrosis who underwent advanced therapies (37% vs 13%, p = 0.09). There was a trend of lower likelihood of receiving advanced HF therapies in the advanced-fibrosis group, only 1 heart transplantation and 7 left ventricular assist devices, but it did not reach statistical significance (35% vs 56%, p = 0.06). After adjustment for confounders, degree of liver fibrosis was an independent predictor of mortality (odds ratio 6.2; 95% 1.27 to 30.29, p = 0.02). We conclude that advanced liver fibrosis is common among patients with stage D HF who undergo evaluation for advanced HF surgical therapies and significantly increases 1-year mortality. Further larger studies are needed to support our findings., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2023. Published by Elsevier Inc.)

Hydroxychloroquine is a disease-modifying antirheumatic drug used for various rheumatological conditions. Its long-term use is well-known to have toxic effects on cardiac muscle cells. We present a biopsy-proven case of hydroxychloroquine-induced cardiotoxicity with detailed histopathological and imaging findings. The patient was referred to our heart failure clinic for concerns of reduction in left ventricular ejection fraction despite being on guideline-directed medical therapy. She had been diagnosed with rheumatoid arthritis, pulmonary hypertension and then subsequently heart failure with reduced ejection fraction 5 years ago. The evaluation included right heart catheterisation, cardiac MRI and endomyocardial biopsy. Light and electron microscopy showed myocyte hypertrophy and vacuolar change, abnormal mitochondria, myeloid bodies and curvilinear bodies. These findings were specific for hydroxychloroquine-induced cardiomyopathy. This case highlights the importance of clinical monitoring, early suspicion and consideration of drug-induced toxicities as a culprit for heart failure., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There is paucity of data regarding durable left ventricular assist device (LVAD) outcomes in patients with chronic kidney disease (CKD) stages 3-5 and CKD stage 5 on dialysis (end-stage renal disease [ESRD])., Methods and Results: We conducted a retrospective study of Medicare beneficiaries with ESRD and a 5% sample of patients with CKD with an LVAD (2006-2018) to determine 1-year outcomes using the United States Renal Data System database. The LVAD implantation, comorbidities, and outcomes were identified using appropriate International Classification of Diseases, 9th and 10th edition codes. We identified 496 patients with CKD and 95 patients with ESRD who underwent LVAD implantation. The patients with ESRD were younger (59 years vs 66 years; P < .001), had more Blacks (40% vs 24.6%, P = .009), compared with the CKD group. The 1-year mortality (49.5% vs 30.9%, P < .001) and index mortality (27.4% vs 16.7%, P = .014) rates were higher for patients with ESRD. A subgroup analysis showed significantly higher mortality in ESRD vs CKD 3 (49.5% vs 30.2%, adjusted P = .009), but no significant difference in mortality between stage 3 vs 4/5 (30.2% vs 30.8%, adjusted P = .941). There was no significant difference in secondary outcomes (bleeding, stroke, and sepsis/infection) during follow-up between the 2 groups., Conclusions: Patients with ESRD undergoing LVAD implantation had significantly higher index and 1-year mortality rates compared with patients with CKD., Competing Interests: Declaration of Competing Interest None of the authors have any direct conflicts of interest related to this article., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: There is a paucity of data on readmission rates and predictors of readmissions in cardiogenic shock patients after contemporary Extracorporeal Membrane Oxygenation (ECMO) use., Methods: Using the Nationwide Readmission Database, we included adult patients (≥18 years old) hospitalized between January to November 2016-2018 for cardiogenic shock requiring ECMO support. Thirty-day readmission rates, associated variables, and predictors of readmission were assessed., Results: A total of 10,723 patients underwent ECMO for cardiogenic shock. After excluding patients who died ( n  = 5602; 52%) and who underwent LVAD or OHT during index admission ( n  = 892; 8%), 4229 patients discharged alive were included. Of those, 694 (16.4%) were readmitted within 30 days. The median time to readmission was 10 days. Diabetes mellitus (OR = 1.77; 95% CI 1.32-2.37), chronic liver disease (OR = 1.35; 95% CI 1.03-1.77), and prolonged LOS (≥30 days; OR = 1.38; 95% CI 1.05-1.81) were associated with increased risk of 30-day readmissions while heart failure diagnosis (OR = 0.69; 95% CI 0.50-0.95) and short-term hospital post-discharge care (OR = 0.53; 95% CI 0.28-0.99) conferred a lower risk. Sepsis, followed by congestive heart failure, was the most common readmission diagnoses., Conclusions: Patients with CS requiring ECMO support have high mortality and high 30-day readmission rates, with sepsis being the leading cause of readmissions followed by heart failure., Competing Interests: Joseph E. Tonna, MD reports a relationship with LivaNova and Philips Healthcare that includes: speaking and lecture fees and travel reimbursement. Joseph E. Tonna, MD reports a relationship with The National Institutes of Health, The National Heart, Lung, And Blood Institute that includes: funding grants., (© 2021 Published by Elsevier Inc.)

Background: Evaluation of patients with acute decompensated heart failure includes symptom review, biomarker measurement and comorbidity assessment. Early objective evaluation of functional status is generally not performed., Aim: To investigate whether a simple low-impact functional assessment and measurement of sarcopenia would be safe, feasible and predictive of hospital length of stay and all-cause 30-day hospital readmission., Methods: We administered 3-minute bicycle ergometry and hand grip strength tests at admission and discharge to patients for whom a decision to admit for heart failure management was made in the emergency department. Associations were examined between test results and length of stay and 30-day readmission. Exclusion criteria included acute coronary syndrome, hypoxia, end-stage renal disease, dementia/delirium and inability to sit at bedside. The Kansas City Cardiomyopathy Questionnaire-12, the Patient Health Questionnaire-2 and the visual analogue scale for dyspnoea were administered at admission, the visual analogue scale at discharge and the Kansas City Cardiomyopathy Questionnaire-12 at 30 days., Results: Fifty patients were enrolled: 58% were female; the mean age was 66.2±12.5 years; 24% had heart failure with preserved ejection fraction. Bicycle ergometry variables did not correlate with outcomes. Change in handgrip strength correlated with readmission, but not after adjustment (r partial =0.14; P=0.35). Total diuretic dose correlated with length of stay; only discharge visual analogue scale and baseline lung disease had significant adjusted correlations with readmission., Conclusions: Functional assessment in the emergency department of patients admitted for heart failure did not predict outcomes. However, the prognostic value of these assessments for decision-making about disposition (admission or discharge) may still be warranted., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background: Targeted treatment for decompensated right heart failure (RHF) with or without left heart failure is lacking. Vasopressin antagonists (vaptans) may offer an option by increasing urine output and fluid mobilization when used in acute decompensated RHF without impacting blood pressure or renal function, both common complications of loop diuretics., Methods and Results: We searched electronic medical records from 2 institutions over 4 years for patients with RHF treated with vaptans. Urine output, creatinine, BUN and sodium, 1 day pre- versus 1 day post-vaptan initiation were compared. Baseline (admission) pre-vaptan values for patients with RHF who met inclusion criteria (n = 112) were RAP, median (interquartile range) = 19 (13-24) mmHg; cardiac index, mean ± standard deviation = 1.8 ± 0.4 L/min/m2; BNP, 1078 (523-1690) pg/ml; creatinine clearance of 51 (39-69) ml/min, BUN, 37 (26-54) mg/dl, and serum [Na+] 132 (126-135) mEq/L. Most patients (n = 103/112) received intravenous inotrope (prior to vaptan, n = 91). Overall length of stay was 27 (16-43) days. Vaptan treatment (90% tolvaptan, 10% conivaptan) was associated with increased 24 h urine output, 1517 (906-2394) vs 2337 (1425-3744) mL, p = 0.005, and [Na+], 127 (124-130) vs 130 (126-135) mEq/L, p = 0.001, without significant change in Cr or BUN. Furosemide IV dose equivalent decreased or remained unchanged in 75% of patients at 24 h and 64% at 72 h compared to the 24 h prior to vaptan use., Conclusion: Vaptans were associated with a significant increase in urine output and serum sodium with an apparent reduction or stabilization of furosemide equivalent dosing in the early treatment period in patients with decompensated RHF. Vaptans may offer a management option for patients failing conventional diuretic-based treatment., (Copyright © 2018. Published by Elsevier B.V.)

Background: The Hospital Readmissions Reduction Program provides incentives to hospitals to reduce early readmissions for heart failure (HF), acute myocardial infarction (AMI), and pneumonia (PNE)., Methods and Results: To examine the contribution of each diagnosis to readmissions penalty size, data were obtained from the Center for Medicare and Medicaid Services, American Hospital Association, and United States Census Bureau including number of cases; readmissions payment adjustment factor (values <1 indicate a penalty for excess readmissions), excess readmission ratio (ERR, or ratio of adjusted predicted readmission based on comorbidities, frailty, and individual patient demographics to expected probability of readmission at an average hospital) for each diagnosis, hospital teaching status, bed number, and zip code socioeconomic status. Of 2,228 hospitals with ≥25 cases per diagnosis, 1,636 received a penalty. Univariate correlation coefficients between penalty and ERR were -0.66, -0.61, and -0.43 for HF, PNE, and AMI, respectively (all P < .001). Correlation between ERRs was greatest for PNE and HF (0.30; P < .001) and weakest for PNE and AMI (0.12; P < .001). In regression analyses, the HF ERR explained the most variance in the penalty (R(2) range 0.21-0.44)., Conclusion: HF ERR, not the number of cases, was related to penalty magnitude. These findings have implications for the design of hospital-based quality initiatives regarding readmissions., (Copyright © 2015 Elsevier Inc. All rights reserved.)