COVID-19 morbidity in patients after orthotopic heart transplantation - single center clinical observation.

INTRODUCTION: The study is a prospective clinical observation of patients after orthotopic heart transplantation in a large academic medical center in relation to COVID-19 morbidity. The study population was comprised of 552 patients. All patients were consulted and advised by telephone as regards the prophylaxis of SARS-CoV-2 infection. Hospital and outpatient follow-ups were limited to the minimum. Preventive modification of immunosuppression was not recommended in relation to the pandemic. Three patients with multiple comorbidities (a woman aged 60, a man aged 59, and another man aged 83; 2.25 years, 5.5 years, and 7.5 years after heart transplantation, respectively) and one patient with concomitant arterial hypertension (a woman aged 48, 5.5 years after heart transplantation) presented with a symptomatic COVID-19 infection. Three of the patients were on tacrolimus immunosuppression, and both female patients were additionally on therapy with mycophenolate mofetil, which was discontinued following the diagnosis of infection. One male patient received combined therapy of cyclosporine A and mycophenolate mofetil. The 60-year-old woman presented with gastrointestinal manifestations of the COVID-19 infection which were of moderate severity. The recovery was achieved. The 59-year-old man presented with myocardial infarction, exacerbated renal insufficiency that required hemodialysis and cardiorespiratory failure complicated by bacterial sepsis. As a result, the patient died. The 83-year-old male patient reporting fever, myalgia, fatigue, cough and dyspnea was admitted to hospital and deceased due to septic shock two days after admission. The 48-year old woman who presented with mild symptoms of the upper respiratory tract infection recovered after two weeks. Symptomatic treatment was used in all the patients. Another male patient (aged 45 years, 8 years after orthotopic heart transplant with no significant comorbidities) was an asymptomatic carrier of SARS-CoV-2 and remained under hospital care. CONCLUSIONS: Of 552 patients after orthotopic heart transplantation, two SARS-CoV-2-related deaths were reported.

Outcome Prediction After Coronary Surgery and Redo Surgery for Bleeding (From the KROK Registry).

OBJECTIVES: To assess the reliability of EuroSCORE II in an entire population after isolated coronary artery surgery and separately among patients who underwent redo surgery due to bleeding, and to create a model predicting hospital death among patients who underwent redo surgery owing to bleeding. DESIGN: Retrospective study based on data from the Polish National Registry of Cardiac Surgical Procedures. SETTING: Multi-institutional study. PARTICIPANTS: The study comprised 41,353 patients who underwent isolated coronary artery surgery in Poland between January 2012 and December 2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: EuroSCORE II reliability was estimated using the area under the receiver operating characteristics curve (AUC), the observed-to-expected surgical mortality ratio (O/E), and the Hosmer-Lemeshow test. Parameters of the function correcting the original EuroSCORE II were determined using the least squares method. The original score was adjusted using a created formula. Among the 41,353 patients, 1,406 (3.4%) underwent reexploration. Even though EuroSCORE II was reliable in predicting hospital mortality in the entire population (AUC 0.76, O/E ratio 1.08), it greatly underestimated mortality for patients who required reexploration (AUC 0.74, O/E ratio 4.33). In this subpopulation, the worst performance of the EuroSCORE II was noted among patients with the lowest predicted mortality (0.50%-0.82%) Accurate calibration was obtained by adding a coefficient and creating a nomogram. CONCLUSIONS: EuroSCORE II was reliable in a Polish population undergoing isolated coronary surgery. After redo surgery for bleeding, the observed mortality was much higher than in the overall coronary population, but the rate was made more accurate by adding a coefficient to the initially calculated EuroSCORE II.

Effect of COVID-19 Pandemic on Complications and Mortality in the Early Postoperative Period After Heart Transplantation.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) outbreak directly impacted heart transplantation (HT) surgery activity. Reallocating resources and converting surgical intensive care units to COVID-19 facilities led to reduced accessibility and quality of health care facilities to heart recipient patients. AIM: To study the effect of the COVID-19 pandemic on heart transplantation activity and outcomes in the early postoperative period. METHODS: Retrospective data analysis of patients undergoing orthotopic heart transplantation in our institution from March 2018 to February 2022. The patient population (N = 281) included 223 (79.4%) men and 58 (20.6%) women. The perioperative data of the prepandemic group, March 2018 to February 2020 (N = 130), and the pandemic group, March 2020 to February 2022 (N = 151), were compared. RESULTS: We found differences in preoperative inotropic support between the groups (N = 43 (33.1%) vs N = 72 (47.7%), P < .05), respectively). The number of urgent HTs increased during the COVID-19 pandemic (N = 51 (39.2%), vs N = 72 (47.7%), P = .155). Analyzed groups did not differ according to renal, pulmonary, or neurology complications. Intensive care unit (ICU) standing time was longer in the pandemic group (6 days [3-12] vs 11 days [5-12], P < .001). CONCLUSION: We found that during the COVID-19 pandemic, the number of end-stage heart failure recipients requiring cardiac support increased. Extended time of ICU standing in the pandemic group may be related to the COVID-19 pandemic. Although some efforts have been made to reduce the impact of the pandemic, more research is required.

Post-COVID-19 Era In Heart Transplantation and Its Impact on the Early Postoperative Period After Surgery.

BACKGROUND: End-stage heart failure patients were at increased risk for acquiring COVID-19 infection and progression to severe disease, given multiple health care contacts and underlying health conditions. Understanding the outcomes of such patients will help risk-stratify and guide optimization before heart transplant surgery. The aim of this study was to evaluate the impact of the COVID-19 pandemic on heart transplantation activity and outcomes in the early postoperative period. METHODS: Retrospective data analysis of patients undergoing orthotopic heart transplantation in our institution from March 2020 to July 2023. The patient population (N = 208) included 176 (84.6%) men and 32 (15.4%) women. The perioperative data of the pandemic group, March 2020 to February 2022 (N = 151), and the post-pandemic group, March 2022 to July 2023 (N = 57), were compared. RESULTS: The number of patients requiring inotropic support increased during the post-COVID-19 era (N = 48 [84.2%], vs N = 72 [47.7%], P < .001). There were no differences in renal complications. Duration of mechanical ventilation was longer in the post-pandemic group (19 hours [14-24] vs 14 hours [9-28], P < .05). CONCLUSIONS: The extended duration of mechanical ventilation in the post-pandemic group may be related to the patient's preoperative condition. The number of heart transplant recipients with end-stage heart failure requiring inotropic support increased in the post-COVID-19 era. Although some efforts have been made to reduce the impact of the pandemic, more research is required.

Assessment of Selected Parameters of Heart Donors and Recipients and Their Impact on the Transplantation Result.

OBJECTIVE: To evaluate the impact of heart donors and recipients parameters on the outcomes after orthotopic heart transplantation (OHT). METHODOLOGY: Two hundred fifteen patients who underwent OHT from 2020 to 2023 were analyzed. RESULTS: Average donors age 36.3 (±13.1) years, 74 women (34.42%), BMI 25.3 (±4.99), Na+ concentration 153.7 (±11.8) mmol/L. Mean intraventricular septum thickness 10.0 (±2.2) mm, left ventricular end-diastolic diameter 44.3 (±6) mm, ejection fraction 60.3 (±7.92) %. Median procalcitonin was 0.6 ng/mL. Levonor was used in 75.8%, Empressin in 4.2%, Dopamine in 5.1%, Dobutamine in 3.7%, and Adrenaline in 3.7% of donors. The most common cause of death: intracranial injury (34.42%). Cardiopulmonary resuscitation occurred in 34%, alcoholism in 20.9%, nicotinism in 16.3%, and drug addiction in 7.4% of donors. Mean aortic cross-clamping time was 200.3 (±48.8) minutes. Intra-aortic balloon pump (IABP) after OHT required 6.1%, extra corporeal membrane oxygenation (ECMO) 6.1%, and renal dialysis 36% of recipients. The 1-year mortality rate was 19.1%. Death after OHT correlated with: longer aortic cross-clamping time (207.6 vs 198.59 minutes, P = .292), longer extracorporeal circulation time (196.3 vs 186.47 minutes, P = .335), lower Empressin dose (median 0.01 vs 0.02 j.m/min, P = .03) in donors, longer postoperative mechanical ventilation (mean 101.46 vs 23.09 hours, P = .001), more frequent dialysis, IABP or ECMO (P = .001) and older age of the recipient (51.2 vs 44.8 years, P = .014). Previous cardiac surgery or any surgical intervention after transplantation significantly influenced mortality. The remaining donor factors had no impact on the OHT result. CONCLUSIONS: Identification of risk factors in the donor and recipient may improve treatment outcomes after OHT.

Thyroid Dysfunction in Advanced Heart Failure Patients and Its Correlation with Amiodarone Therapy: A Two-Year Study.

(1) Background: Advanced heart failure often accompanies ventricular arrhythmias, necessitating antiarrhythmic therapies. Amiodarone, commonly used for this purpose, may induce thyroid dysfunction due to its high iodine content. However, the prevalence and correlation of thyroid dysfunction with amiodarone in end-stage heart failure patients remain unclear. Aim: This study aimed to evaluate the prevalence and types of thyroid dysfunction and their association with amiodarone among 200 patients diagnosed with advanced heart failure eligible for transplantation. (2) Methods: Consecutively enrolled patients received treatment following the European Society of Cardiology guidelines and were followed-up for two years. Ventricular arrhythmias affected 58.5% of the cohort, with 24.5% receiving amiodarone therapy. (3) Results: Thyroid metabolism dysfunction was evident in 61 patients, notably overrepresented in women (p = 0.0028). Hyperthyroidism (34 patients) and hypothyroidism (27 patients) were observed, with a significant amiodarone-related correlation. Despite this, thyroid dysfunction was not associated with increased mortality among the studied group. (4) Conclusions: Thyroid dysfunction is prevalent in advanced heart failure patients, with a notable proportion linked to amiodarone. However, its presence does not correspond to higher mortality rates. Understanding these associations is crucial for effective management in this patient population. Further exploration is warranted to refine approaches to thyroid dysfunction in refractory heart failure.

Pediatric Heart Transplantation in the Context of Severe Pulmonary Hypertension Secondary to Restrictive Cardiomyopathy-Case Report.

The aim of this study is to analyze the feasibility of performing an isolated heart transplant in patients with severe pulmonary hypertension as a result of restrictive cardiomyopathy. The results present the clinical course from the diagnosis of restrictive cardiomyopathy at the age of 2 until the heart transplant at 8 years old. Initially, the patient was considered for multiorgan transplantation, heart and lungs, due to extremely high pulmonary resistance. However, due to the prolonged waiting period for a donor and the worsening condition of the child, a decision was made to perforate the atrial septum with the implantation of an atrial flow regulator system. After conducting control hemodynamic measurements, the qualification was changed to an isolated heart transplant, accepting the high operative risk associated with the still elevated pulmonary resistance index of 4.9 Wood units. This study describes the medical problems that occurred during postoperative treatment. The patient underwent an orthotopic heart transplant in her eighth year of life. Postsurgery, complications were observed, including generalized seizures and heart transplant rejection reaction. Immunosuppressive therapies were applied, and efforts were made to combat anemia and electrolyte disorders. While the cardiovascular system and heart parameters improved, there were some difficulties in controlling heart rhythm and stabilizing electrolyte levels.

Personal Resources and Expectations and Health Behaviors Among Solid Organ Transplant Recipients-A Multicenter Study.

BACKGROUND: The long-term success of organ transplantation (Tx) depends on the transplant recipient's ability to self-manage symptoms, treatment, lifestyle changes, and psychosocial consequences. Health behavior (HB) determinants include personality traits such as optimism, self-efficacy, and health locus of control. PURPOSE: Assessing the relationship between personal resources and expectations and health behaviors of organ transplant recipients. MATERIAL AND METHODS: The study was conducted between 01/04/2018 and 30/10/2019 at 3 transplant centers in Poland. The study group consisted of 243 Tx recipients of kidney, heart, liver, and lung. The Health Behavior Inventory, Multidimensional Health Locus of Control Scale (MHLC), General Self-Efficacy Scale, Dispositional Optimism Scale, and Hospital Anxiety and Depression Scale were used to collect data. FINDINGS: The study group had medium levels of dispositional optimism (mean 15) and high levels of self-efficacy (mean 30.18). The MHLC scale was dominated by a belief in the influence of others and an internal locus of control over one's health. The respondents presented a high level of HB (mean 92.09). A positive relationship was found between personal resources (self-efficacy and optimism), MHLC and HB. The presence of depression and anxiety negatively affected personal resources and internal locus of health control and HB in terms of a positive mental attitude. Type of Tx differentiated internal locus of health control and HB. Predictors of HB were dispositional optimism, self-efficacy, influence of others with health locus of control, symptoms of depression, age and time since transplantation-explaining between 6.1% and 14.5% of health behavior categories. CONCLUSIONS: To improve health practices among organ recipients, strengthening their personal resources is recommended. It is necessary to form an internal locus of control for adherence to positive HB.

Utility of 64-Slice Coronary Computed Tomography Angiography in Heart Transplant Recipients.

BACKGROUND: Graft vasculopathy is a leading cause of death after heart transplantation (HTx). Diagnosing cardiac allograft vasculopathy (CAV) within this patient group poses significant challenges. This study aimed to evaluate the safety and efficacy of coronary computed tomographic angiography (CCTA) in patients after HTx. METHODS: We enrolled 107 consecutive HTx recipients (26 women, mean age 50 ± 17 years); all were ≥3 years post-HTx with minimal or no evidence of CAV in a prior coronary angiography performed a minimum of 2 years before the current examination. The inclusion criteria comprised an estimated glomerular filtration rate (eGFR) of ≥30, absence of new heart failure symptoms, and no contraindications to iodine contrast or CT scans. All patients underwent a 64-slice CCTA. In cases of minimal or no changes, noninvasive follow-up examinations were conducted. Significant changes in CT prompted additional coronary angiography. RESULTS: Of the enrolled participants, 9 exhibited minimal changes; 98 displayed no changes in coronary angiography. The median time since transplant was 7 years, with IQR of 4 to 11.25 years. Significant changes were excluded in 98 patients. Among the 9 patients with suspected significant CAV, significant changes were confirmed in 8 patients, resulting in percutaneous transluminal coronary angioplasty (PTCA) performed in 6. One patient from this group died shortly after PTCA. No cardiovascular incidents were observed within the remaining group. The median follow-up period was 539 (IQR = 289-654 days). The mean left ventricular ejection fraction at follow-up was 58% ± 5% compared with 58% ± 4% at baseline. At follow-up, the mean eGFR was 64 ± 18 mL/kg/1.73 m2 compared with the baseline value of 67.2 mL/kg/1.73 m2. CONCLUSIONS: CCTA appears to offer a secure and efficient means of assessment in HTx recipients.

Systemic Sclerosis as a Challenge for Heart Transplantation: A Case Report.

OBJECTIVE: To assess the principles of qualification and the range of organ transplantation in a patient with diagnosis of system sclerosis with pulmonary manifestation and severe myocardial insufficiency. METHODS: We present the case of a 43-year-old patient with confirmed systemic sclerosis with pulmonary manifestations and biventricular heart insufficiency after disease exacerbation and sudden cardiac arrest in the pulseless electrical activity (PEA) mechanism with effective resuscitation, with increasing shortness of breath and the need for inotropes and levosimendan infusion without a significant improvement in his general status. Owing to the diagnosis of a systemic disease with no option for pharmacologic or any other treatment for heart failure, he was reevaluated and put on an urgent waiting list for isolated heart transplantation. After 7 days, heart transplantation was performed. Given the risk of disease progression and the possibility of future lung transplantation, the pleural cavities were untouched. The standard immunosuppression protocol was followed with the use of rabbit antithymocyte globulin. RESULTS: The patient was extubated at 24 hours after heart transplantation. The results of endomyocardial biopsies performed during the hospital stay and at a 6-month follow-up were negative. The patient was discharged to home after 22 days of an uneventful hospital stay. CONCLUSIONS: Scleroderma as an autoimmunologic disease remains a challenge for the transplantation team as a possible progressive multiorgan insufficiency requiring qualification for organ transplantation. The course of the disease varies depending on the form of systemic sclerosis. Careful assessment, qualification, and determination of appropriate preprocedure and postprocedure immunosuppressive treatment are essential to an uncomplicated course of treatment.

Lung Transplantation in Patients With Pulmonary Hypertension With Extracorporeal Membrane Oxygenation (ECMO) Support: 5-Year Experience.

Lung transplantation (LTx) is the only treatment option of patients (pts) with pulmo-nary hypertension (PH) when pharmacologic treatment is unsatisfactory. ECMO is essential during LTx in every patient with pulmonary arterial hypertension and in most patients with sec-ondary PH. This is a retrospective, single-center study comparing LTx outcomes in patients with and without PH covering a 5-year experience. In the years 2018-2023, 219 LTx were performed, of which 56 (25.6%) with ECMO support, among which PH was diagnosed in 34pts (60.7%) in WHO groups 1,3,4: 19pts, 14pts. and 1pt respectively. The veno-arterial type of ECMO was used in patients with PH as intraoperative support (n = 34; 100%). The early (30-day) and long-term survival (1 year) of patients with and without PH did not differ statistically: 91.2% (95% CI: 82.1%-100%) vs. 77.3% (95% CI: 82.1%-100%)(P = .48) and 53.0% (95% CI: 36.6%-76.7 %) vs. 41.3% (95%CI: 23.1-74.0) (P = .48) respectively and the median hospitalization time from ECMO weaning to dis-charge was also comparable: 31 days (Q1-Q3: 21-40; IQR 20) vs. 28 days (Q1-Q3: 24-42; IQR :18) (P = .99). Patients with or without PH undergoing LTx with ECMO have comparable survival and hospital stay outcomes despite being the most challenging of all lung diseases treated with lung transplantation.

Lung Transplantation in Patients With Systemic Scleroderma-Description of the First Consecutive Cases in Poland: Case Series Report and a Short Literature Review.

Pulmonary complications of systemic scleroderma (SSc), such as interstitial lung disease and pulmonary hypertension (PH), are responsible for up to 60% of deaths among patients. For many years, most centers considered SSc a contraindication to lung transplantation (LTx); however, recent publications show that appropriately selected SSc candidates for LTx give results comparable to patients with idiopathic PH or idiopathic pulmonary fibrosis. This paper presents the cases of a 60-year-old male patient (patient 1) and a 42-year-old female patient (patient 2) diagnosed with SSc in 2019 and 2013, respectively. In both patients, interstitial-fibrotic changes in the lungs leading to respiratory failure were confirmed by high-resolution computed tomography as well as pulmonary hypertension (WHO group 3), which was also diagnosed during right heart catheterization. In both cases, despite pharmacotherapy, pulmonary fibrosis progressed, leading to severe respiratory failure. The patients were referred for LTx qualification. LTx was possible to consider in patients due to the lack of significant changes in other internal organs. Double LTx was successfully performed in both patients (patient 1-July 19, 2022; patient 2-September 14, 2022). They were discharged from the hospital in good condition on the 22nd and 20th postoperative day, respectively. LTx is a last-chance therapy that saves lives among patients with extreme respiratory failure in the course of SSc. It prolongs and improves the quality of life. The selection of appropriate patients is key to the success of the procedure.

Mechanical circulatory support in patients with congenital heart disease: a European Registry for Patients with Mechanical Circulatory Support (EUROMACS) study.

OBJECTIVES: This study aims to explore characteristics and clinical outcomes of patients with congenital heart disease (CHD) in the European Registry for Patients with Mechanical Circulatory Support (EUROMACS). METHODS: This is a retrospective study of EUROMACS participants receiving MCS as bridge-to-transplant, possible bridge-to-transplant, or rescue therapy/bridge-to-recovery from 2011 to 2023 (n = 5340). Adult and paediatric cohorts were analysed separately. The primary outcome was mortality on MCS; secondary outcomes included recovery, transplant and complications including bleeding, cerebrovascular events, and sepsis. RESULTS: Among adult patients, mortality at 1-year was 33.3% among the CHD cohort vs 22.1% in the non-CHD cohort. Adult CHD patients had higher hazards of mortality within the first year after MCS implantation [hazard ratios 1.98, 95% confidence interval (CI) 1.35-2.91, P < 0.001] and bleeding events (subdistribution hazard ratios 2.10, 95% CI 1.40-3.16, P < 0.001) compared with non-CHD patients. Both associations remained significant after accounting for multiple mediators. Among paediatric patients, mortality at 1 year was 22.1% in the CHD cohort vs 17.3% in the non-CHD cohort (hazard ratios 1.39, 95% CI 0.83-2.32, P = 0.213). CONCLUSIONS: Adult and paediatric patients with CHD on MCS have higher adverse event risk compared with non-CHD MCS patients, though children did not have greater risk of mortality. As the number of CHD patients requiring advanced heart failure management continues to grow, these findings can enhance informed decision-making. CLINICAL TRIAL REGISTRATION NUMBER: Registry name: EUROMACS.

Torque Teno Virus (TTV)-A Potential Marker of Immunocompetence in Solid Organ Recipients.

Torque Teno Virus (TTV), first discovered in 1997, is a non-pathogenic, highly prevalent virus with a notable presence in the human virome. TTV has garnered attention as a potential indicator of immunocompetence in recipients of solid organ transplants. In this review, we discuss the role of TTV as a potential marker for immunosuppression optimization, prediction of graft rejection, and as an indicator of opportunistic infections. We discuss TTV's behavior over the course of time after transplantation, TTV's implications in different immunosuppressive regimens, and potential utility in vaccinations. The review synthetizes findings from various studies depicting its potential clinical utility for future personalized patient care.

Long-term results of pediatric heart transplantations: Single-center experiences.

BACKGROUND: Heart failure (HF) is characterized by significant mortality in both adults and children. Characteristics of pediatric HF are feeding problems, poor weight gain, exercise intolerance, or dyspnea. These changes are often accompanied by endocrine disorders. The main causes of HF are congenital heart defects (CHD), cardiomyopathies, arrhythmias, myocarditis, or heart failure secondary to oncological treatment. Heart transplantation (HTx) is the method of choice for treatment of end-stage HF in pediatric patients. AIMS: This article aimed to summarize the single-center experience in heart transplantation in children. METHODS: Between 1988 and 2021 in the Silesian Center for Heart Diseases in Zabrze, 122 pediatric cardiac transplantations were performed. In the group of recipients with failing Fontan circulation, HTx was performed in 5 children. The study group was evaluated for the postoperative course: rejection episodes depending on the medical treatment scheme, coinfections, and mortality. RESULTS: One-, 5-, and 10-year survival rates between 1988 and 2001 were 53%, 53%, and 50%, respectively. One-, 5-, and 10-year survival rates between 2002 and 2011 were 97%, 90%, and 87%, respectively; between 2012 and 2021 (1-year of follow-up), the survival rate was 92%. The main cause of mortality both in early and late periods after transplantation was graft failure. CONCLUSIONS: Cardiac transplantation in children remains the main method of treatment for endstage heart failure. Our results at both early and long-term posttransplant periods are comparable to those obtained in the most experienced foreign centers.

Gut Microbiome in Patients after Heart Transplantation-Current State of Knowledge.

The human gut microbiota include over 10 trillion microorganisms, such as bacteria, fungi, viruses, archaea, and protozoa. Many reports indicate the strong correlation between dysbiosis and the severity of cardiovascular diseases. Microbiota seem to interact with the host's alloimmunity and may have an immunomodulatory role in graft rejection processes. In our study, we present the current state of the knowledge of microbiota in heart transplant recipients. We present up-to-date microbiota diagnostic methods, interactions between microbiota and immunosuppressive drugs, the immunomodulatory effects of dysbiosis, and the available strategies (experimental and clinical strategies) to modulate host microbiota.

Does the induction immunotherapy (basiliximab) influence the early acute cellular rejection index after orthotopic heart transplantation?- Preliminary assessment report.

The study aimed to determine the influence of induction therapy on the acute cellular rejection (ACR) index in adult heart transplant recipients during the one-year observation. The study population consisted of 256 consecutive adult patients (pts), aged 51.5 (±11.9) years, 199 (77%) men treated with orthotopic heart transplantation (OHT) in the period between 2015 and 2020 in a single high-volume heart transplant center. The endomyocardial biopsies (EMBs) were performed according to the protocol consisting of 7 protocolary EMBs for up to 3 months and 10 EMBs for up to one year after OHT. The rejection index (ACRI) was calculated as the number of scheduled EMBs with the ACR ≥ 2 divided by the total number of protocolary EMBs. The study population was divided into two groups according to the application of basiliximab. The total number of pts. who received basiliximab was 10 (3.9%). The main indications for the usage of the induction therapy were heart retransplantation, mechanical circulatory support (MCS), severe renal insufficiency (eGFR <30 mL/min/1.73 m2), and a panel of reactive antibody (PRA) > 10%. In the group with induction, the mean age was 49 (±14) years; 3 (30%) patients had the MCS prior to OHT, and 3 (30%) patients had heart retransplantation. Four (40%) patients had diabetes mellitus, and 4 (40%) patients had severe renal insufficiency. As maintenance therapy during the observation period, tacrolimus was given to 10 (100%) patients, everolimus to 2 (20%) patients, and MPA to 9 (90%) patients. In the group with no induction, the mean age was 51.8 (±12) years, MCS was used in 56 (23%) patients, 2 (0.8%) patients were retransplanted; 10 (4%) patients had eGFR <30 mL/min/1.73 m2 and 58 (24%) patients had diabetes. Tacrolimus was administered to 243 (99%) patients, cyclosporine to 3 (1%), everolimus to 40 (16%), and mycophenolate to 245 (99.6%) heart recipients. The median one-year ACRI was 0.0, IQR:0.0-0.08 in the group with induction vs. 0.077, IQR: 0.0-0.154 with no induction; p = 0.11. ACRI up to three months was significantly higher in the entire cohort in comparison to up to one year (P < 0.01). The multivariate analysis showed that only everolimus implementation and younger age at the time of transplant influenced patients' mortality rate (P < 0.01). Significant graft rejections (≥ 2R ISHLT) are most common in the first three months after OHT. Patients who are initially at high risk of significant cellular rejection may benefit from induction therapy.

Sacubitril/valsartan for cardioprotection in breast cancer (MAINSTREAM): design and rationale of the randomized trial.

AIMS: In recent years, survival in patients with breast cancer has increased. Despite the improvement in outcomes of those patients, the risk of treatment-related cardiotoxicity remains high, and its presence has been associated with a higher risk of treatment termination and thus lower therapeutic efficacy. Prior trials demonstrated that a preventive initiation of heart failure drugs, including the renin-angiotensin-aldosterone inhibitors, might reduce the risk of treatment-related cardiotoxicity. However, to date, no study investigated the efficacy of sacubitril/valsartan, a novel antineurohormonal drug shown to be superior to the previous therapies, in the prevention of cardiotoxicity in patients with early-stage breast cancer, which is the aim of the trial. METHODS AND RESULTS: MAINSTREAM is a randomized, placebo-controlled, double-blind, multicentre, clinical trial. After the run-in period, a total of 480 patients with early breast cancer undergoing treatment with anthracyclines and/or anti-human epidermal growth factor receptor 2 drugs will be randomized to the highest tolerated dose of sacubitril/valsartan, being preferably 97/103 mg twice daily or placebo in 1:1 ratio. The patients will be monitored, including routine transthoracic echocardiography (TTE) and laboratory biomarker monitoring, for 24 months. The primary endpoint of the trial will be the occurrence of a decrease in left ventricular ejection fraction by ≥5% in TTE within 24 months. The key secondary endpoints will be the composite endpoint of death from any cause or hospitalization for heart failure, as well as other imaging, laboratory, and clinical outcomes, including the occurrence of the cancer therapy-related cardiac dysfunction resulting in the necessity to initiate treatment. The first patients are expected to be recruited in the coming months, and the estimated completion of the study and publication of the results are expected in December 2027, pending recruitment. CONCLUSIONS: The MAINSTREAM trial will determine the efficacy and safety of treatment with sacubitril/valsartan as a prevention of cardiotoxicity in patients with early breast cancer (ClinicalTrials.gov number: NCT05465031).

Serologic Status According Severe Acute Respiratory Syndrome Coronavirus 2 in Patients After Orthotopic Heart Transplantation.

BACKGROUND: The SARS-CoV-2 pandemic is ongoing. In this context, patients after organ transplantation are especially endangered because of their increased susceptibility to infections. Real effectiveness of vaccinations against SARS-CoV-2 and exposition to the virus in populations after organ transplantation is still being assessed. METHODS: We investigated 371 adult patients (82.7% men, 17.3% women), aged 54 ± 14 years, with a median time from transplantation of 1296 days (interquartile range, 473-400 days) after orthotopic heart transplantation consecutively admitted to the transplant center between February and September 2021. SARS-CoV-2 spike protein antibodies were assessed quantitatively by Elecsys Anti-SARS-CoV-2 S. Data according to past COVID-19 infection and vaccination were compared with the test results. Among the whole group, 59 patients were unvaccinated and had no past COVID-19 infection, 200 patients had a full course of vaccination (2 doses) with an mRNA vaccine, 1 patient had received a viral vector vaccine, 11 patients had had a single dose of an mRNA vaccine, and 99 patients had previously had a COVID-19 infection. Median time from vaccination to antibody assessment was 54 days (interquartile range, 30-76 days). AIM: The aim of this study was to determine exposure to the virus among patients after heart transplantation before vaccination and humoral response to the vaccination and assess the role of antispike antibodies in the prevention of infection. RESULTS: After vaccination, 22.3% had no antibodies (45 patients), 47.3% had titers between 0.8 U/mL [0.82 binding antibody units (BAU)/mL] and 250 U/mL (257.25 BAU/mL; 95 patients), and 30.2% had titers above 250 U/mL (257.25 BAU/mL; 61 patients). After a single dose of vaccine, 63% patients had no antibodies. In the group of unvaccinated patients, 3 patients had titers above 250 U/mL (257.25 BAU/mL; 5.1%) and 12 patients had titers up to 250 U/mL (257.25 BAU/mL; 20.3%). In patients after COVID-19 infection, only 2% did not show antispike antibodies, and in 61.4% the titers were above 250 U/mL (257.25 BAU/mL). In the group of patients infected after the full course of vaccination (4 patients after a single dose and 2 after 2 doses), none of the patients developed antibodies after vaccination. Up to the end of September 2021, none of the patients with antibodies against SARS-CoV-2 developed COVID-19. CONCLUSIONS: The presence of spike protein antibodies may be a relevant marker of effective vaccination. In patients after heart transplantation, exposure to SARS-CoV-2 is high.

Patients After Orthotopic Heart Transplantation With COVID-19: Are We Fast Enough With Vaccinations?

BACKGROUND: Patients after orthotopic heart transplantation (HTx) are especially susceptible to infections owing to permanent need for immunosuppression. Vaccinations against COVID-19 have been available since January 2021 and are recommended in organ recipients. AIM: The aim of this study was to analyze COVID-19 susceptibility and mortality in HTx and number of patients with COVID-19 previously vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). PATIENTS AND METHODS: We analyzed a whole cohort of 552 patients after HTx who were SARS-CoV-2 positive and remained under surveillance of the transplantation center during March 2020 to September 2021. RESULTS: Among 552 patients after HTx, 10 were COVID-19 survivors prior to transplantation and 103 had SARS CoV-2 infection after transplantation. Mean age of patients with COVID-19 was 55.6 (±14) years, and mean time from transplantation to SARS-CoV-2 infection was 2856 (±2596) days (range, 16-9569 days; interquartile range, 397-4763 days). Among the patients who were COVID-19 positive, 15 were asymptomatic, 10 died, and 51 infections occurred in the era of vaccinations. In the group of patients who were positive for COVID-19 in 2021, 6 received only a single dose of the mRNA vaccine and 3 were vaccinated twice. Among the vaccinated patients with COVID-19, 2 died of severe COVID-19: 1 after a single dose and 1 after 2 standard doses of the vaccine. CONCLUSION: We observed high susceptibility to SARS-CoV-2 infection in the group of patients after HTx. The majority of patients infected in 2021 did not received the vaccine. Vaccination does not fully protect against severe COVID-19 in patients after HTx.