No abstract

: 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 for 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 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 approach 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 in 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.

Cardiogenic shock (CS) with variable systemic inflammation may be responsible for patient heterogeneity and the exceedingly high mortality rate. Cardiovascular events have been associated with clonal haematopoiesis (CH) where specific gene mutations in haematopoietic stem cells lead to clonal expansion and the development of inflammation. This study aims to assess the prevalence of CH and its association with survival in a population of CS patients in a quaternary centre.

Background:Mutations in sarcomeric genes are found in 60-70% of individuals with familial forms of hypertrophic cardiomyopathy (HCM). However, this estimate refers to northern hemisphere populations. The molecular-genetic profile of HCM has been subject of few investigations in Brazil, particularly in the south of the country.Objective:To investigate mutations in the sarcomeric genes MYH7, MYBPC3 and TNNT2 in a cohort of HCM patients living in the extreme south of Brazil, and to evaluate genotype-phenotype associations.Methods:Direct DNA sequencing of all encoding regions of three sarcomeric genes was conducted in 43 consecutive individuals of ten unrelated families.Results:Mutations for CMH have been found in 25 (58%) patients of seven (70%) of the ten study families. Fourteen (56%) individuals were phenotype-positive. All mutations were missense, four (66%) in MYH7 and two (33%) in MYBPC3. We have not found mutations in the TNNT2 gene. Mutations in MYH7 were identified in 20 (47%) patients of six (60%) families. Two of them had not been previously described. Mutations in MYBPC3 were found in seven (16%) members of two (20%) families. Two (5%) patients showed double heterozygosis for both genes. The mutations affected different domains of encoded proteins and led to variable phenotypic expression. A family history of HCM was identified in all genotype-positive individuals.Conclusions:In this first genetic-molecular analysis carried out in the south of Brazil, we found mutations in the sarcomeric genes MYH7 and MYBPC3 in 58% of individuals. MYH7-related disease was identified in the majority of cases with mutation.

Aims: Treatment with mechanical circulatory support (MCS) has been proposed to mitigate mortality in cardiogenic shock (CS). However, there is a lack of data on MCS programs implementation and the effect of the learning curve on its outcomes in limited resources countries such as Brazil. Methods: Prospective cohort of patients with CS admitted in four tertiary-care centers treated with Impella CP or veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Clinical outcomes were peri-procedural complications, short-term mortality rate, and the centers’ learning curve. The cohort was divided into two periods: from April 2017 to July 2018 ( n = 24), and from August 2018 to December 2020 ( n = 25). Results: The study enrolled 49 patients [age 59 (43–63) years; 34 (70%) males]. The most common causes for CS were acute myocardial infarction in 22 (45%) and acute decompensation of chronic heart failure in 10 (20%). VA-ECMO was employed in 35 (71%) and Impella CP in 14 (29%) of patients. Overall complications occurred in 37 (76%) of patients, where major bleeding in 19 (38%) was the most common. The overall mortality rate was 61%, but it was lower in the second period (40%) in comparison to the first period (83%), p = 0.002. The learning curve analysis showed a decrease in the mortality rate after 40 consecutive cases. Conclusions: Implementation of a temporary MCS program for refractory CS in a limited resource country is feasible. The learning curve effect might have played a role on survival rate since high morbimortality has decreased within time reaching optimal results by the end of the study.

Background To evaluate the prognostic value of peak serum lactate and lactate clearance at several time points in cardiogenic shock treated with temporary mechanical circulatory support (MCS) using veno-arterial extracorporeal membrane oxygenation (VA-ECMO) or Impella CP®. Methods Serum lactate and clearance were measured before MCS and at 1 h, 6 h, 12 h, and 24 h post-MCS in 43 patients at four tertiary-care centers in Southern Brazil. Prognostic value was assessed by univariable and multivariable analysis and receiver operating characteristic (ROC) curves for 30-day mortality. Results VA-ECMO was the most common MCS modality (58%). Serum lactate levels at all time points and lactate clearance after 6 h were associated with mortality on unadjusted and adjusted analyses. Lactate levels were higher in non-survivors at 6 h, 12 h, and 24 h after MCS. Serum lactate > 1.55 mmol/L at 24 h was the best single prognostic marker of 30-day mortality [area under the ROC curve = 0.81 (0.67–0.94); positive predictive value = 86%). Failure to improve serum lactate after 24 h was associated with 100% mortality. Conclusions Serum lactate was an important prognostic biomarker in cardiogenic shock treated with temporary MCS. Serum lactate and lactate clearance at 24 h were the strongest independent predictors of short-term survival.

Hypertrophic cardiomyopathy is a prevalent genetic disease characterized by left ventricular hypertrophy, presenting dynamic obstruction of outflow tract with subaortic gradient happening at rest in 30% of the cases. It is attributed to the intricate interaction between the anterior mitral leaflet, the interventricular septum and altered flow vectors generated in left ventricle along with changes in outflow tract geometry. Mitral regurgitation in varying degrees is found with or without association with structural deformities of the valve apparatus. The exercise echocardiogram evidences latent obstruction easily induced by exercise in 60 to 75% of nonobstructive forms. The determination of the gradient under this condition must be considered in routine investigation of patients with mild or no obstruction at rest. The evaluation of hypertrophic cardiomyopathy incorporates methods based on the ultrasound image, which, along with MRI, allow recognizing ventricular obstruction generating mechanisms, thus facilitating the diagnosis and management of obstructive and latent obstructive forms.

In HCM, occurrence of ventricular arrhythmias by Holter was associated with the degree of LVH assessed by echocardiography through MWT and BMI.