Medical decisions in organ donors and heart transplant candidates with history of COVID-19 infection: An international practice survey.

BACKGROUND: A growing proportion of transplant donors and recipients have a history of COVID-19 infection. This study sought to characterize clinical practice after recipient or donor COVID-19 infection. METHODS: An online survey was distributed to heart transplant clinicians through a professional society message board and social media. Responses were collected between September 29 and November 5, 2021. RESULTS: There were 222 health care professionals (68% transplant cardiologists, 22% transplant surgeons, 10% other) across diverse geographic regions who completed the survey. While there was significant variation in donor acceptance, as it relates to past and current COVID-19 infection, the respondents were fairly cautious: 28% would not typically accept a donor with a history of COVID-19 regardless of the infection course and > 80% would not accept donors who had evidence of myocardial dysfunction during past COVID-19 infection, or who died of COVID-19 or its complications. The timing of candidate reactivation on the waiting list after COVID-19 infection also varied and often diverged from scenarios addressed by social guidelines. Eighty-one percent of the respondents felt COVID-19 vaccine should be mandatory before transplant, but this rate varied by geographic region. CONCLUSION: Our results reflect evolving experience of the heart transplant field at a time of lack of high-quality evidence. In the absence of longer-term outcome data for donors and transplant candidates with history of COVID-19 infection, clinicians remain cautious; however, this approach will likely need to be refined as an increasing proportion of the population will continue to be infected with COVID-19.

Post Heart Transplantation Coronary Artery Fistula and Coronary Artery Aneurysm Successfully Managed With the Implantation of Covered Stents.

Coronary-to-cardiac chamber fistulae and coronary aneurysms are potential complications after heart transplantation. In the setting of exercise intolerance and large fistulae at major coronary vessels, covered stents may provide an effective interventional strategy.

A Comprehensive and Contemporary Review on Immunosuppression Therapy for Heart Transplantation.

Heart transplantation is the standard of therapy for patients with end-stage heart disease. Since the first human-to-human heart transplantation, performed in 1967, advances in organ donation, surgical techniques, organ preservation, perioperative care, immunologic risk assessment, immunosuppression agents, monitoring of graft function and surveillance of long-term complications have drastically increased recipient survival. However, there are yet many challenges in the modern era of heart transplantation in which immunosuppression may play a key role in further advances in the field. A fine-tuning of immune modulation to prevent graft rejection while avoiding side effects from over immunosuppression has been the vital goal of basic and clinical research. Individualization of drug choices and strategies, taking into account the recipient's clinical characteristics, underlying heart failure diagnosis, immunologic risk and comorbidities seem to be the ideal approaches to improve post-transplant morbidity and survival while preventing both rejection and complications of immunosuppression. The aim of the present review is to provide a practical, comprehensive overview of contemporary immunosuppression in heart transplantation. Clinical evidence for immunosuppressive drugs is reviewed and practical approaches are provided. Cardiac allograft rejection classification and up-to-date management are summarized. Expanding therapies, such as photophoresis, are outlined. Drug-to-drug interactions of immunosuppressive agents focused on cardiovascular medications are summarized. Special situations involving heart transplantation such as sarcoidosis, Chagas diseases and pediatric immunosuppression are also reviewed. The evolution of phamacogenomics to individualize immunosuppressive therapy is described. Finally, future perspectives in the field of immunosuppression in heart transplantation are highlighted.

Impaired Right Ventricular Function in Heart Transplant Rejection / Disfunção Ventricular Direita e Rejeição em Transplante Cardíaco

Abstract Background: The practice of screening for complications has provided high survival rates among heart transplantation (HTx) recipients. Objectives: Our aim was to assess whether changes in left ventricular (LV) and right ventricular (RV) global longitudinal strain (GLS) are associated with cellular rejection. Methods: Patients who underwent HTx in a single center (2015 - 2016; n = 19) were included in this retrospective analysis. A total of 170 biopsies and corresponding echocardiograms were evaluated. Comparisons were made among biopsy/echocardiogram pairs with no or mild (0R/1R) evidence of cellular rejection (n = 130 and n = 25, respectively) and those with moderate (2R) rejection episodes (n=15). P-values < 0.05 were considered statistically significant Results: Most patients were women (58%) with 48 ± 12.4 years of age. Compared with echocardiograms from patients with 0R/1R rejection, those of patients with 2R biopsies showed greater LV posterior wall thickness, E/e' ratio, and E/A ratio compared to the other group. LV systolic function did not differ between groups. On the other hand, RV systolic function was more reduced in the 2R group than in the other group, when evaluated by TAPSE, S wave, and RV fractional area change (all p < 0.05). Furthermore, RV GLS (−23.0 ± 4.4% in the 0R/1R group vs. −20.6 ± 4.9% in the 2R group, p = 0.038) was more reduced in the 2R group than in the 0R/1R group. Conclusion: In HTx recipients, moderate acute cellular rejection is associated with RV systolic dysfunction as evaluated by RV strain, as well as by conventional echocardiographic parameters. Several echocardiographic parameters may be used to screen for cellular rejection.

Resumo Fundamento: A prática de triagem para complicações tem proporcionado altas taxas de sobrevida entre pacientes que receberam transplante cardíaco (TC). Objetivos: Visamos avaliar se alterações no strain longitudinal global (SLG) do ventrículo esquerdo (VE) e do ventrículo direito (VD) estão associadas à rejeição celular. Métodos: Pacientes que foram submetidos à TC em um único centro (2015 - 2016; n = 19) foram incluídos nesta análise retrospectiva. Foram avaliados um total de 170 biópsias com ecocardiogramas correspondentes. Foram realizadas comparações entre pares de biópsia/ecocardiograma com nenhuma ou leve (0R/1R) evidência de rejeição celular (n = 130 e n = 25, respectivamente) e aqueles com episódios de rejeição moderada (2R) (n = 15). Foram considerados estatisticamente significativos os valores de p < 0,05. Resultados: A maioria dos pacientes eram mulheres (58%) com idade média de 48 ± 12,4 anos. Em comparação com os ecocardiogramas dos pacientes com rejeição 0R/1R, os pacientes com biópsias 2R apresentaram maior espessura da parede posterior do VE, relação E/e' e relação E/A, em comparação com o outro grupo. A função sistólica do VE não diferiu entre os grupos. Por outro lado, a função sistólica do VD foi reduzida no grupo 2R em comparação ao outro grupo, quando avaliada por TAPSE, onda S e variação fracional da área do VD. Adicionalmente, SLG VD (−22,97 ± 4,4% no grupo 0R/1R vs. −20,6 ± 4,9% no grupo 2R, p = 0,038) foi reduzido no grupo 2R, em comparação com o grupo 0R/1R. Conclusão: Em pacientes de TC, rejeição celular aguda moderada está associada à disfunção sistólica do VD, avaliado pelo strain do VD, bem como por parâmetros ecocardiográficos convencionais. Vários parâmetros ecocardiográficos podem ser utilizados para realizar triagem para rejeição celular.

Critical Care Management of the Acute Postimplant LVAD Patient.

Left ventricular assist devices (LVADs) improve survival and quality of life in refractory end-stage heart failure. However, the therapy itself is associated with some degree of morbidity and mortality at highest risk during the first 30 days postimplantation. Management of the patient with a freshly implanted LVAD requires an in-depth understanding of the acute postimplant period and common critical care issues including coagulopathy, hemodynamic lability, and metabolic derangements. This requires meticulous hemostatic control and a firm understanding of hemodynamic principles that focus on optimizing end-organ perfusion, right-ventricular function, and measured LVAD titration. This contemporary practical guide to management of the acute postimplant LVAD patient includes a focused approach to troubleshooting common LVAD issues that may arise from the operating room to discharge from critical care.

Impaired Right Ventricular Function in Heart Transplant Rejection.

BACKGROUND: The practice of screening for complications has provided high survival rates among heart transplantation (HTx) recipients. OBJECTIVES: Our aim was to assess whether changes in left ventricular (LV) and right ventricular (RV) global longitudinal strain (GLS) are associated with cellular rejection. METHODS: Patients who underwent HTx in a single center (2015 - 2016; n = 19) were included in this retrospective analysis. A total of 170 biopsies and corresponding echocardiograms were evaluated. Comparisons were made among biopsy/echocardiogram pairs with no or mild (0R/1R) evidence of cellular rejection (n = 130 and n = 25, respectively) and those with moderate (2R) rejection episodes (n=15). P-values < 0.05 were considered statistically significant Results: Most patients were women (58%) with 48 ± 12.4 years of age. Compared with echocardiograms from patients with 0R/1R rejection, those of patients with 2R biopsies showed greater LV posterior wall thickness, E/e' ratio, and E/A ratio compared to the other group. LV systolic function did not differ between groups. On the other hand, RV systolic function was more reduced in the 2R group than in the other group, when evaluated by TAPSE, S wave, and RV fractional area change (all p < 0.05). Furthermore, RV GLS (-23.0 ± 4.4% in the 0R/1R group vs. -20.6 ± 4.9% in the 2R group, p = 0.038) was more reduced in the 2R group than in the 0R/1R group. CONCLUSION: In HTx recipients, moderate acute cellular rejection is associated with RV systolic dysfunction as evaluated by RV strain, as well as by conventional echocardiographic parameters. Several echocardiographic parameters may be used to screen for cellular rejection.

Expanding benefits from cardiac resynchronization therapy to exercise-induced left bundle branch block in advanced heart failure.

Indications of cardiac resynchronization therapy (CRT) do not include exercise-induced left bundle branch block, but functional impairment could be improved with CRT in such cases. A 57-year-old woman with idiopathic dilated cardiomyopathy (ejection fraction 23%) presented with New York Heart Association Class IV and recurrent hospitalizations. During heart transplant evaluation, a new onset of intermittent left bundle branch block was observed on the cardiopulmonary exercise test. CRT was implanted, and 97% resynchronization rate was achieved. In 12 month follow-up, both clinical and prognostic exercise parameters improved. In patients with heart failure with reduced ejection fraction and no left bundle branch block at rest, exercise test can uncover electromechanical dyssynchrony that may benefit from CRT.

Heart Transplantation Cost Composition in Brazil: A Patient-Level Microcosting Analysis and Comparison With International Data.

BACKGROUND: Advanced heart failure (HF) therapies, such as heart transplantation, are resource intensive and costly. In Brazil, only one-fifth of the estimated population need is fulfilled. We examined cost expenditures of heart transplants in a public institution in Brazil. METHODS AND RESULTS: We used microcosting analysis (time-driven activity-based costing) to examine total costs and individual cost components related to the index transplant hospital admission of all consecutive heart transplant recipients at a single center from July 2015 to June 2017. Average total cost for the 27 patients included was US$ 74,341 which exceeds the reimbursement value per patient by 60%. Major cost drivers were hospital structure and personnel, similarly to what is observed in the United States (US) and other developed countries. Total costs for index transplant admission were ∼50% lower than in the US, but approximate to values reported in some European countries. Costs of heart transplantation in Brazil were lower than those reported for developed countries, and higher than national reimbursement values. CONCLUSIONS: Advanced microcosting methodologies represent an important quality contribution to economic studies in health care and may provide insights for transplant-related health care policies in developing countries.

Duration of corticosteroid use and long-term outcomes after adult heart transplantation: A contemporary analysis of the International Society for Heart and Lung Transplantation Registry.

BACKGROUND: Long-term corticosteroid (CS) maintenance remains an effective option for immunosuppression following heart transplantation. We used the International Society for Heart and Lung Transplantation Registry to examine characteristics and long-term survival among heart transplant recipients with different duration of CS therapy. METHODS: Primary adult heart recipients transplanted between 2000 and 2008 who survived at least 5 years were categorized into three groups according to CS use: early withdrawal (≤2 years) (EARLY D/C), late withdrawal (between 2 and 5 years) (LATE D/C), or long-term use (>5 years) (LONG-TERM). Recipient and donor characteristics, post-transplant morbidities, and mortality were compared among groups. Kaplan-Meier was used to estimate survival up to 10 years post-transplant. RESULTS: The study cohort included 8161 recipients (2043 in EARLY D/C; 2031 in LATE D/C; and 4087 in LONG-TERM). LONG-TERM use of CS decreased over time, from 60% in 2000 to 43% in 2008, while EARLY D/C increased from 19% to 33%, respectively. Survival at 10 years after transplant was lower among the LONG-TERM group (73% vs EARLY D/C 82% vs LATE D/C 80%; P < 0.0001). CONCLUSIONS: In this large multinational cohort, the practice of long-term CS maintenance was associated with lower long-term survival compared with shorter CS use.

The prognostic significance of frailty compared to peak oxygen consumption and B-type natriuretic peptide in patients with advanced heart failure.

Frailty assessment has become an integral part of the evaluation of potential candidates for heart transplantation and ventricular assist device (HTx/VAD). The impact of frailty, as a heart failure risk factor or to identify those who will derive the greatest benefit with HTx/VAD remains unclear. The aim of this study was to evaluate the independent prognostic relevance of frailty assessment from peak oxygen consumption (peak VO2 ) or B-type natriuretic peptide (BNP) on mortality in patients referred for advanced heart failure therapies. Frailty was measured using modified Fried frailty criteria. In 201 consecutive patients, during a median follow-up of 17.5 months (IQR 11-29.2), there were 25 (12.4%) deaths. One-year survival was 100%, 94%, and 78% in nonfrail, prefrail, and frail patients, respectively (log rank P = .0001). Frailty was associated with a twofold increase risk of death (HR 2.01, P < .0001, 95% CI 1.42-2.84). When adjusted for BNP or peak VO2 , frailty was not associated with a significant risk of all-cause death. However, when peak VO2 is stratified into two categories (≥12 mL/kg/min vs <12 mL/kg/min), frailty was associated with increased mortality in patients with a lower peak VO2 (HR 1.72, P = .006).

Transcoronary gradient of plasma microRNA 423-5p in heart failure: evidence of altered myocardial expression.

CONTEXT: Elevated plasmatic microRNAs (miRs) are observed in heart failure (HF). However, the cardiac origin of these miRs remains unclear. OBJECTIVE: We calculated transcoronary gradients of miR-29b, miR-133a and miR-423-5p in 17 outpatients with stable systolic HF and in controls without structural cardiac disease. MATERIALS AND METHODS: MicroRNAs were measured by quantitative real-time polymerase chain reaction. RESULTS: Positive transcoronary miR gradients were observed in patients with HF but not in controls (p = 0.03). B-type natriuretic peptide (BNP) moderately correlated with the transcoronary gradients of miR-133a and miR-423-5p. DISCUSSION AND CONCLUSIONS: The difference in transcoronary gradients between HF outpatients and controls suggests that miR-423-5p has a cardiac origin. The positive correlation between miR-423-5p and BNP transcoronary gradients supports this hypothesis.

Anemia in heart failure: association of hepcidin levels to iron deficiency in stable outpatients.

BACKGROUND: Anemia is a prevalent condition in heart failure with multiple potential causes. The complex interaction between iron stores, hepcidin, inflammation and anemia is poorly comprehended. We tested the hypothesis that, in stable heart failure patients with anemia, hepcidin is associated with iron deficiency status irrespective of inflammation. METHODS AND RESULTS: Stable systolic heart failure outpatients with and without anemia underwent a complete iron panel, erythropoietin, hepcidin and tumor necrosis factor (TNF)-α assessment. Sixty outpatients were studied. Anemic patients (n = 38, mean hemoglobin 11.4 ± 1 g/dl) were older (69.6 ± 9.6 vs. 58 ± 10.8 years old, p < 0.01) compared with nonanemic patients (n = 22, mean hemoglobin 13.8 ± 1.1 g/dl). Iron deficiency was present in 42% of patients with anemia. TNF-α and hepcidin were 29 and 21% higher in patients with anemia, respectively, compared to nonanemic patients; however, no correlations were found between hepcidin and TNF-α levels. Hepcidin levels in the lower tertile (<31.7 ng/ml) were strongly associated with iron deficiency (OR 16.5, 95% CI 2.2-121.2; p < 0.01). CONCLUSION: In stable heart failure patients with anemia, hepcidin levels may be more importantly regulated by patients' iron stores than by inflammation.

Serum procollagen type III is associated with elevated right-sided filling pressures in stable outpatients with congestive heart failure.

Elevated filling pressures are associated with heart failure deterioration, but mechanisms underlying this association remain poorly understood. We sought to investigate whether or not elevated filling pressures are associated with increased collagen turnover, evaluated by procollagen type III aminoterminal peptide (PIIINP) levels, in stable systolic heart failure. Eighty patients with heart failure with severe systolic dysfunction (ejection fraction 26 +/- 7%) were included. Patients underwent simultaneous echocardiogram with evaluation of haemodynamic parameters and blood sampling for PIIINP measurement. Mean PIIINP level was 6.11 +/- 2.62 microg l(-1). PIIINP was positively associated with estimated right atrial pressure (RAP) (r = 0.36; p = 0.001). Mean PIIINP values were 5.04 +/- 2.42 microg l(-1) in patients with estimated RAP < or = 5 mmHg, and 7.59 +/- 2.54 microg l(-1) in those with RAP > 15 mmHg (p < 0.01). In conclusion, elevated right-side filling pressures are associated with evidence of active extracellular matrix turnover, as indicated by elevated PIIINP levels, in stable systolic heart failure. Activation of extracellular matrix turnover may be implicated in the accelerated progression of heart failure syndromes seen in patients with persistent congestion.

Effects of 5'-phosphodiesterase four-week long inhibition with sildenafil in patients with chronic heart failure: a double-blind, placebo-controlled clinical trial.

BACKGROUND: The effects of chronic inhibition of 5'-phosphodiesterase with sildenafil on functional capacity, ventilatory efficiency, oxygen uptake, pulmonary hypertension, and endothelial function in chronic heart failure (CHF) are unknown. METHODS: We conducted a randomized, double-blind, placebo-controlled trial to assess the acute (1 hour after 50 mg by mouth) and chronic (4 weeks after 50 mg 3 times per day by mouth) effects of sildenafil in outpatients with CHF. The outcomes were cardiopulmonary exercise test parameters (chronic effect), echocardiographic-derived pulmonary artery systolic pressure, and plethysmography-derived forearm blood flow (acute and chronic effects). RESULTS: Nineteen patients with CHF (48 +/- 12 years) with an ejection fraction of 28% +/- 6% were studied. Patients who received sildenafil (n = 11) showed improved maximal oxygen uptake, ventilatory efficiency, and oxygen uptake kinetics. Sildenafil decreased pulmonary artery systolic pressure levels at 60 minutes and at 4 weeks compared with changes after placebo (P = .004 for group and time interaction). Improvement in ventilatory efficiency was positively associated with reductions in pulmonary artery systolic pressure. Patients allocated to placebo demonstrated a trend toward decreased forearm blood flow after reactive hyperemia, whereas this remained unchanged in patients allocated to sildenafil. CONCLUSIONS: Sildenafil administration for 4 weeks in stable outpatients with CHF improves functional capacity, ventilatory efficiency, oxygen uptake kinetics, and pulmonary hypertension. These effects may be mediated in part by improvements in endothelial function.

A hemodynamically oriented echocardiography-based strategy in the treatment of congestive heart failure.

BACKGROUND: The therapeutic applicability of echocardiographic evaluations remains poorly defined in heart failure (HF). We hypothesized that an individualized echocardiography-guided strategy would be feasible and significantly reduce morbidity compared with the conventional clinically oriented treatment. METHODS AND RESULTS: We conducted a single-center clinical trial comparing an echocardiography-guided strategy aimed at achieving a near-normal hemodynamic profile and a conventional clinically oriented strategy for HF management. The echocardiography-guided strategy was based on sequential echocardiograms to evaluate hemodynamically derived parameters. Pharmacologic therapy was guided according to a predefined protocol. The primary efficacy end point was time to the first event of combined all-cause mortality and all-cause hospitalization or emergency department visit up to 1 year of follow-up. We studied 96 outpatients with HF, enrolled from 1999 to 2003, with predominantly nonischemic cause and a mean left ventricular ejection fraction of 26% +/- 6%. Event-free survival at a mean follow-up of 230 days was 58.5% with the echocardiography-guided strategy and 36.5% with the clinically based strategy (relative risk = 0.54, 95% confidence interval = 0.31-0.97, P = .04). More patients in the echocardiography-based group received high-dose loop diuretics (absolute difference of 19%, P = .02) and hydralazine (absolute difference of 30%, P < .001). Significant reductions of estimates of pulmonary artery systolic pressure (mean difference of -9 mm Hg, P = .02) and systemic vascular resistance index (mean difference of -700 dyn x sec x m2 x cm5, P = .02) were observed in the echocardiography-guided group. CONCLUSION: A hemodynamically oriented echocardiography-based strategy is feasible and decreases HF morbidity. This benefit could be attributed in part to the rational and individualized use of higher doses of diuretics and vasodilators.