The risk of transmission of the novel coronavirus (SARS-CoV-2) with human heart valve transplantation: evaluation of cardio-vascular tissues from two consecutive heart donors with asymptomatic COVID-19.

We report on two living donors of explanted hearts while receiving heart transplantation that tested positive for SARS-CoV-2 on the day of donation, although clinically asymptomatic. They underwent heart transplantation for ischaemic and hypertrophic obstructive cardiomyopathy, respectively. After evaluation of donor hearts, we cryopreserved and stored two pulmonary valves for clinical application and one aortic valve for research. Light microscopy of myocardium, mitral valve and aortic and pulmonary arterial wall and RT-PCR SARS-CoV-2 test of myocardium, mitral and tricuspid valve and aortic wall for detection of SARS-CoV-2 were performed. Presence of ACE2 in tissues was assessed with immunostaining. Light microscopy revealed a mild eosinophilic myocarditis in the ischemic cardiomyopathy heart, whereas enlarged cardiomyocytes with irregular nucleus and some with cytoplasmic vacuoles in the hypertrophic obstructive cardiomyopathy heart. Aortic and pulmonary wall were histologically normal. Immunostaining revealed diffuse presence of ACE2 in the myocardium of the heart with eosinophilic myocarditis, but only discrete presence in the hypertrophic cardiomyopathy heart. The RT-PCR SARS-CoV-2 test showed no presence of the virus in tested tissues. Despite eosinophilic myocarditis in the ischemic cardiomyopathy heart, no viral traces were found in the myocardium and valve tissues. However, ACE2 was present diffusely in the ischemic cardiomyopathy heart. SARS-CoV-2 could not be detected in the cardiac tissues of these COVID-19 asymptomatic heart donors. In our opinion, clinical application of the valves from these donors presents negligible risk for coronavirus transmission. Nonetheless, considering the uncertainty regarding the risk of virus transmission with the human tissue transplantation, we would not release in any case the pulmonary valve recovered from the eosinophilic myocarditis heart. In contrast, we may consider the release of the pulmonary valve from the dilated cardiomyopathy heart only for a life-threatening situation when no other similar allograft were available.

Fatal Toxoplasma gondii Dissemination in a Heart Transplant Recipient: Description of a Case.

A 45-year-old heart transplant recipient presented with fever, anorexia, asthenia, and lethargy. She had received heart transplantation only 5 weeks earlier for primary systemic amyloidosis with severe cardiac involvement. Serum sodium was low, and tacrolimus through level was high. Blood cultures and serology tests for infection were negative, and atypical pneumonia was suspected. Despite broad antibiotic, antiviral, and antifungal treatment, the patient clinical condition rapidly deteriorated and she died within three days of admission. Postmortem examination revealed a disseminated Toxoplasma gondii infection as a result of donor (+)/recipient(-) mismatch for Toxoplasma serology. Although very rare, toxoplasmosis in heart transplant recipient should be suspect in case of neurological deficit and respiratory symptoms. Prophylaxis treatment is recommended in case of mismatch.

Long-term survival (>20 years) following heart transplantation.

AIM: Only a few papers with patients surviving more than 15 years after heart transplantation have been reported. Herein we report the characteristics of patients transplanted between 1984 and 1989 who are long-term survivors (>20 years). Survival after transplant, recipient and donor age and aetiology of heart failure were also compared with patients transplanted in the decades 1990-1999 and 2000-2009. METHODS: Our Heart Transplant Program Database and medical records of all cardiac transplants performed in our centre from July 1984 to 1989 were reviewed. Primary endpoint of the study was the long-term survival and secondary end points were the incidence of transplant-related complications over time. RESULTS: Forty-five transplants were performed in 1984-1989, 41 patients were male, median age was 46 years (IQR: 39-55), median donor age was 24 years (19-29) and mean graft ischemic time was 134±64 minutes. The actuarial survival of this cohort was 77.8%, 64.4%, 48.9%, 35.6% and 24.2% at 1, 5, 10, 15 and 20 years, respectively. Univariate Cox regression analysis revealed the female gender, the graft ischemic time, the recipient-donor gender mismatch, a diagnosis of diabetes and the number of acute rejection episodes during the first year post-transplant as significant risk factors adversely affecting long-term survival. Cardiac allograft vasculopathy is the main cause of death. The mean recipient and donor age and the graft ischemic time have progressively increased over time but survival has not changed. CONCLUSION: The long-term outcome of heart transplantation is noteworthy. The main limiting factor for survival is the allograft vasculopathy. Considering the tremendous advances in the immunosuppressive therapy and in the understanding of CAV pathophisyology, we can hope for even better results in the next years.

[Global evaluation of the heart in heart transplant recipients using dual-source computed tomography]. / Valoración global del corazón en el paciente con transplante cardiaco mediante tomografía computarizada de doble fuente.

In routine clinical practice surveillance of heart transplant recipients is usually performed using echocardiography and conventional coronary angiography. The latter permits diagnosis and follow-up of coronary allograft vasculopathy. However, this procedure is invasive and is not free of complications. Conventional multislice computed tomography (MSCT) has been shown to be a useful non-invasive tool for ruling out coronary artery disease and evaluating cardiac function. However, due to its limited temporal resolution betablocker administration is required, and its usefulness in certain patient populations with restricted response to this medication, such as heart transplant recipients, may therefore be limited. Dual-source CT (DSCT) allows evaluation of the coronary arteries in all individuals independent of their heart rate. In the case presented here, we demonstrate that DSCT may be useful for evaluating cardiac function and ruling out coronary allograft vasculopathy in heart transplant recipients.

Valoración global del corazón en el paciente con transplante cardiaco mediante tomografía computarizada de doble fuente / Global evaluation of the heart in heart transplant recipients using dual-source computed tomography

La ecocardiografía y la coronariografía convencionalson las dos técnicas empleadas en la práctica clínicapara el seguimiento de los pacientes con transplantecardiaco. La coronariografía permite diagnosticar lavasculopatía del injerto, pero se trata de un procedimientoinvasivo no exento de complicaciones. La tomografíacomputarizada multicorte convencional esuna técnica no invasiva útil para descartar enfermedadcoronaria y estudiar la función cardiaca. Sin embargo,debido a su resolución temporal es necesario administrarfármacos betabloqueantes por lo que su utilidad enlos pacientes con escasa respuesta a esta medicación,como los transplantados cardiacos, es limitada. La TCde doble fuente permite estudiar las arterias coronariasen todos los individuos con independencia de su frecuenciacardiaca. En el caso que se presenta se demuestra,además, que puede ser una técnica útil para valorarla función y descartar la vasculopatía del injerto en lospacientes con transplante cardiaco(AU)

In routine clinical practice surveillance of hearttransplant recipients is usually performed using echocardiographyand conventional coronary angiography. Thelatter permits diagnosis and follow-up of coronary allograftvasculopathy. However, this procedure is invasiveand is not free of complications. Conventional multislicecomputed tomography (MSCT) has been shown to be auseful non-invasive tool for ruling out coronary arterydisease and evaluating cardiac function. However, dueto its limited temporal resolution betablocker administrationis required, and its usefulness in certain patientpopulations with restricted response to this medication,such as heart transplant recipients, may therefore belimited. Dual-source CT (DSCT) allows evaluation of thecoronary arteries in all individuals independent of theirheart rate. In the case presented here, we demonstratethat DSCT may be useful for evaluating cardiac functionand ruling out coronary allograft vasculopathy in hearttransplant recipients(AU)

Two-dose daclizumab, tacrolimus, mycophenolate mofetil, and steroid-free regimen in de novo cardiac transplant recipients: early experience.

BACKGROUND: Tacrolimus (TAC) with mycophenolate mofetil (MMF) and a steroid-free regimen seems to have good efficacy in preventing acute rejection in cardiac transplant recipients, although concern exists about nephrotoxicity. Induction therapy with Daclizumab seems to give protection without side effects. Data are lacking about the outcome of 2-dose Daclizumab+TAC+MMF and a steroid-free regimen. MATERIALS AND METHODS: We retrospectively reviewed 28 consecutive de novo heart transplantations performed at a single center between January 2001 and June 2006. Patients received induction therapy with 2-dose Daclizumab. Maintenance immunosuppression included TAC, MMF, and prednisone during the first 6 months. The endpoints were the incidence of acute rejection, patient and graft survival, and clinical tolerability. RESULTS: Among 28 patients of mean age 57 +/- 9 years, 2 subjects (7%) died in the perioperative period due to infections. The mean follow-up was 2.8 +/- 1.5 years. There were no late deaths. Six patients experienced acute rejection (International Society of Heart and Lung Transplantation [ISHLT] >or=3A) that required treatment during the first 3 months. At follow-up, only 3 patients (>or=3A) required treatment. Mean creatinine level increased from 1.08 +/- 0.37 at baseline to 1.08 +/- 0.41 at 1 year (n = 23; P = not significant [NS]) to 1.39 +/- 0.68 (n = 13; P < .05) at 4 years, 1.65 +/- 0.51 (n = 8; P < .05) at 5 years. No patient required replacement therapy. CONCLUSIONS: A steroid-free protocol with 2-dose Daclizumab induction therapy and maintenance with TAC and MMF seemed to be safe to prevent acute rejection. Creatinine levels were slightly but significantly increased.

Impact on renal function of the use of sirolimus in cardiac transplantation.

INTRODUCTION: During the last few years sirolimus has been introduced as an alternative to preserve renal function in transplant recipients receiving calcineurin inhibitors. MATERIALS AND METHODS: We reviewed our results on the use of sirolimus in cardiac transplant recipients. RESULTS: Twenty-seven patients with an average age of 63 years received sirolimus. The average time after transplantation was 73.4 +/- 58.9 months and the average follow-up was 31.7 +/- 18.01 months. Sirolimus was prescribed in 37% of cases due to chronic renal failure (CRF), 14.8% because of cardiac allograft vasculopathy (CAV), 11.1% for tumors, 22.2% de novo, 7.4% for CRF and tumor, and 7.4% for CRF and CAV. Among the patients with CRF (n = 14), there were 5 (35%) on dialysis at the moment of starting the treatment and 1 was retired from dialysis. The other 4 (28.5%) patients had to be treated with dialysis after starting the treatment. In all, 42.8% of the patients with nephropathy maintained stable renal function or improved. Among the 17 (63%) patients who did not require dialysis, there was no significant change in renal function after 6 months or 1, 2, and 3 years follow-up. CONCLUSIONS: The use of sirolimus in cardiac transplantation maintains stable renal function in the majority of patients in the medium term.

[Heart transplant]. / Trasplante cardíaco.

A heart transplant is at present considered the treatment of choice in cases of terminal cardiac insufficiency refractory to medical or surgical treatment. Due to factors such as the greater life expectancy of the population and the more efficient management of acute coronary syndromes, there is an increasing number of people who suffer from heart failure. It is estimated that the prevalence of the disease in developed countries is around 1%; of this figure, some 10% are in an advanced stage and are thus potential receptors of a heart transplant. The problem is that it is still not possible to offer this therapeutic form to all of the patients that require it. Consequently, it is necessary to optimise the results of the heart transplant through the selection of patients, selection and management of donors, perioperative management and control of the disease due to graft rejection. Since the first transplant carried out in 1967, numerous advances and changes have taken place, which has made it possible to increase survival and quality of life of those who have received a new heart. In this article we review the most relevant aspects of the heart transplant and the challenges that are currently faced.

[Cardiac and vascular homograft valves transplant]. / Trasplante de homoinjertos valvulares cardiacos y vasculares.

The advances in the manipulation of human tissues, the development of cryobiology, paediatric cardiac surgery, the impossibility of obtaining an ideal prosthetic cardiac valve and the surgical treatment of cardiovascular infections have revived interest in the use of homografts. The donors of these homografts can be: a) Live donors: aortic and pulmonary valve of the recipient of a heart transplant; b) Multiorgan donors with a diagnosis of death according to neurological criteria, whose heart is rejected for heart transplant; c) Cadaver donors with asystolia of less than 8 hours. Homograft cardiac valves are the substitute of choice in aortic valve endocarditis, patients with counter-indications for anticoagulation, reconstruction of the outflow tract of the right ventricle, aortic valve replacement in children and young adults through the Ross operation, and an optional indication is the aortic valve and/or rising aorta replacement in patients over 60 years of age. Although there are not sufficiently broad series of homogratfs with arterial substitutes, with respect to the number of patients and time of evolution, the results suggest that this can benefit patients with vascular infection, immunodepressed patients or complex patients whose technique during the operation might require a homograft.

Trasplante cardíaco / Heart transplant

El trasplante cardíaco es considerado actualmente como el tratamiento de elección en la insuficiencia cardíaca terminal refractaria a tratamiento médico o quirúrgico. Debido a factores como la mayor esperanza de vida de la población y el manejo más eficaz de los síndromes coronarios agudos, cada vez hay un número mayor de personas que padecen fallo cardíaco. Se estima que la prevalencia de la enfermedad en países desarrollados está en torno al 1%; de éstos, un 10% está en una etapa avanzada y por tanto son potenciales receptores de un trasplante cardíaco. El problema está en que aún no es posible ofrecer esta modalidad terapéutica a todos los pacientes que la requieren. Por consiguiente, se hace necesario optimizar los resultados del trasplante cardíaco mediante la selección de pacientes, selección y manejo de los donantes, manejo perioperatorio y control de la enfermedad por rechazo del injerto. Desde el primer trasplante efectuado en diciembre de 1967, numerosos avances y cambios se han producido, lo que ha permitido aumentar la supervivencia y calidad de vida de quienes han recibido un nuevo corazón. A continuación se revisarán los aspectos más relevantes del trasplante cardíaco y los desafíos que enfrenta en la actualidad

A heart transplant is at present considered the treatment of choice in cases of terminal cardiac insufficiency refractory to medical or surgical treatment. Due to factors such as the greater life expectancy of the population and the more efficient management of acute coronary syndromes, there is an increasing number of people who suffer from heart failure. It is estimated that the prevalence of the disease in developed countries is around 1%; of this figure, some 10% are in an advanced stage and are thus potential receptors of a heart transplant. The problem is that it is still not possible to offer this therapeutic form to all of the patients that require it. Consequently, it is necessary to optimise the results of the heart transplant through the selection of patients, selection and management of donors, perioperative management and control of the disease due to graft rejection. Since the first transplant carried out in 1967, numerous advances and changes have taken place, which has made it possible to increase survival and quality of life of those who have received a new heart. In this article we review the most relevant aspects of the heart transplant and the challenges that are currently faced

Trasplante de homoinjertos valvulares cardiacos y vasculares / Cardiac and vascular homograft valves transplant

Los progresos en la manipulación de los tejidos humanos, el desarrollo de la criobiología, la cirugía cardiaca pediátrica, la imposibilidad de conseguir una prótesis valvular cardiaca ideal y el tratamiento quirúrgico de las infecciones cardiovasculares, han reintroducido el interés para utilizar los homoinjertos. Los donantes de estos homoinjertos pueden ser: a) Donantes vivos: válvula aórtica y pulmonar del receptor de trasplante cardiaco; b) Donantes multiorgánicos con el diagnóstico de muerte según criterios neurológicos, cuyo corazón es rechazado para trasplante cardiaco; c) Donantes cadáveres con asistolia inferior a 8 horas. Los homoinjertos valvulares cardiacos son el sustituto de elección en las endocarditis valvulares aórticas, pacientes con contraindicación para la anticoagulación, reconstrucción del tracto de salida de ventrículo derecho, sustitución valvular aórtica en niños o adultos jóvenes mediante la operación de Ross y es una indicación opcional la sustitución valvular aórtica y/o la aorta ascendente en los pacientes con edad superior a 60 años. Aunque no hay series suficientemente amplias de homoinjertos como sustitutos arteriales, en cuanto a número de pacientes y tiempo de evolución, los resultados sugieren que se pueden beneficiar los pacientes con infección vascular, inmunodeprimidos o los pacientes complejos cuya técnica durante la intervención puede requerir la necesidad de un homoinjerto

The advances in the manipulation of human tissues, the development of cryobiology, paediatric cardiac surgery, the impossibility of obtaining an ideal prosthetic cardiac valve and the surgical treatment of cardiovascular infections have revived interest in the use of homografts. The donors of these homografts can be: a) Live donors: aortic and pulmonary valve of the recipient of a heart transplant; b) Multiorgan donors with a diagnosis of death according to neurological criteria, whose heart is rejected for heart transplant; c) Cadaver donors with asystolia of less than 8 hours. Homograft cardiac valves are the substitute of choice in aortic valve endocarditis, patients with counter-indications for anticoagulation, reconstruction of the outflow tract of the right ventricle, aortic valve replacement in children and young adults through the Ross operation, and an optional indication is the aortic valve and/or rising aorta replacement in patients over 60 years of age. Although there are not sufficiently broad series of homogratfs with arterial substitutes, with respect to the number of patients and time of evolution, the results suggest that this can benefit patients with vascular infection, immunodepressed patients or complex patients whose technique during the operation might require a homograft