COVID-19 complicating perioperative management of LVAD implantation: A case report and systematic review.

The coronavirus 2019 disease (COVID-19) affected 125 million people worldwide and caused 2.7 million deaths. Some comorbidities are associated with worse prognosis and left ventricular assist device (LVAD) recipients are probably part of this high-risk population. We report a 31-year-old male patient who developed COVID-19 during LVAD implantation. His postoperative period was complicated by severe pneumonia and mechanical ventilation (MV) leading to right ventricular failure (RVF) and inotrope necessity. He experienced multiple complications, but eventually recovered. We present a systematic review of LVAD recipients and COVID-19. Among 14 patients, the mean age was 62.7 years, 78.5% were male. A total of 5 patients (35.7%) required MV and 3 patients (21.4%) died. A total of 2 patients (14.2%) had thromboembolic events. This case and systematic review suggest LVAD recipients are at particular risk of unfavorable outcomes and they may be more susceptible to RVF in the setting of COVID-19, particularly during perioperative period.

Epipericardial fat necrosis as cause of chest pain in patient after heart transplantation.

Epipericardial fat necrosis is an uncommon clinical condition of unknown etiology. It typically presents as acute pleuritic chest pain and should be differentiated from acute pulmonary embolism and acute coronary syndrome. This condition is diagnosed by characteristic chest computed tomography findings of an ovoid mediastinal fatty lesion with intrinsic and surrounding soft-tissue stranding. Treatment of epipericardial fat necrosis includes the administration of anti-inflammatory agents, and symptoms usually resolve within a few days after treatment initiation. This disease entity has rarely been reported since it was first described in 1957. Most current knowledge of epipericardial fat necrosis is based on case reports that describe this condition in previously healthy individuals. We present the case of a 39-year-old woman with a history of heart transplant, who presented with chest pain secondary to epipericardial fat necrosis. Serial computed tomography revealed lesion resolution after appropriate treatment.

Renin-angiotensin System Antagonists and Beta-blockers in Prevention of Anthracycline Cardiotoxicity: a Systematic Review and Meta-analysis. / Antagonistas do Sistema Renina-Angiotensina e Betabloqueadores na Prevenção da Cardiotoxicidade por Antraciclinas: Revisão Sistemática e Metanálise.

BACKGROUND: The evidence supporting the use of renin-angiotensin-aldosterone system (RAAS) inhibitors and beta-blockers for the prevention of anthracycline-induced cardiomyopathy is controversial. OBJECTIVE: We performed a meta-analysis to assess the effectiveness of these drugs in preventing cardiotoxicity. METHODS: The meta-analysis included prospective, randomized studies in adults receiving anthracycline chemotherapy and compared the use of RAAS inhibitors or beta-blockers versus placebo with a follow-up of 6 to 18 months. The primary outcome was change in left ventricular ejection fraction (LVEF) during chemotherapy. Secondary outcomes were the incidence of heart failure, all-cause mortality, and changes in end-diastolic measurement. Heterogeneity was assessed by stratification and meta-regression. A significance level of p < 0.05 was adopted. RESULTS: The search resulted in 17 studies, totaling 1,530 patients. The variation (delta) in LVEF was evaluated in 14 studies. Neurohormonal therapy was associated with a lower delta in pre- versus post-therapy LVEF (weighted mean difference 4.42 [95% confidence interval 2.3 to 6.6]) and higher final LVEF (p < 0.001). Treatment resulted in a lower incidence of heart failure (risk ratio 0.45 [95% confidence interval 0.3 to 0.7]). There was no effect on mortality (p = 0.3). For analysis of LVEF, substantial heterogeneity was documented, which was not explained by the variables explored in the study. CONCLUSION: The use of RAAS inhibitors and beta-blockers to prevent anthracycline-induced cardiotoxicity was associated with less pronounced reduction in LVEF, higher final LVEF, and lower incidence of heart failure. No changes in mortality were observed. (CRD PROSPERO 42019133615).

FUNDAMENTO: As evidências que embasam o uso de inibidores do sistema-renina-angiotensina aldosterona (SRAA) e betabloqueadores para prevenção de cardiomiopatia induzida por antraciclinas são controversas. OBJETIVO: Realizamos uma metanálise para avaliar a eficácia desses medicamentos na prevenção da cardiotoxicidade. MÉTODOS: A metanálise incluiu estudos prospectivos e randomizados com adultos submetidos à quimioterapia com antraciclina e comparou o uso de terapias SRAA ou betabloqueadores versus placebo com seguimento de 6 a 18 meses. O desfecho primário foi alteração da fração de ejeção do ventrículo esquerdo (FEVE) durante a quimioterapia. Os desfechos secundários foram: a incidência de insuficiência cardíaca, mortalidade por todas as causas e alterações na medida do diâmetro diastólico final. A avaliação da heterogeneidade foi realizada por estratificação e meta-regressão. O nível de significância adotado foi p < 0,05. RESULTADOS: A busca resultou em 17 estudos, totalizando 1.530 pacientes. A variação (delta) da FEVE foi avaliada em 14 estudos. A terapia neuro-hormonal foi associada a um menor delta na FEVE pré-terapia versus pós-terapia (diferença média ponderada 4,42 [intervalo de confiança de 95% 2,3 a 6,6]) e maior FEVE final (p < 0,001). O tratamento resultou em menor incidência de insuficiência cardíaca (risk ratio 0,45 [intervalo de confiança de 95% 0,3 a 0,7]). Não houve efeito na mortalidade (p = 0,3). Para a análise da FEVE, foi documentada heterogeneidade substancial, não explicada pelas variáveis exploradas no estudo. CONCLUSÃO: O uso de inibidores do SRAA e betabloqueadores para prevenção da cardiotoxicidade induzida por antraciclinas foi associado a redução menos pronunciada da FEVE, maior FEVE final e menor incidência de insuficiência cardíaca. Não foram observadas alterações na mortalidade. (CRD PROSPERO 42019133615).

Early reduction of pulmonary arterial hypertension in patients using a long-term mechanical ventricular assistance device: a cross-sectional study.

BACKGROUND: Severe pulmonary arterial hypertension (PAH) is a contraindication for heart transplantation (HT). It has been correlated with increased early and late mortality, mainly associated with right ventricular failure. Ventricular assistance devices (VADs) can promote reduction of intracardiac pressures and consequent reduction of PAH over the medium and long terms, thus enabling future candidature for HT. The diminution of early pulmonary pressure within this scenario remains unclear. OBJECTIVE: To evaluate the reduction of PAH and correlate data from right catheterization with the earliness of this reduction. DESIGN AND SETTING: Cross-sectional study in a general hospital in São Paulo, Brazil. METHODS: This was a retrospective analysis on the medical records of patients undergoing VAD implantation in a single hospital. Patients for whom VAD had been indicated as a bridge to candidature for HT due to their condition of constant PAH were selected. RESULTS: Four patients with VADs had constantly severe PAH. Their mean pulmonary artery systolic pressure (PASP) before VAD implantation was 66 mmHg. Over the 30-day period after the procedure, all the patients evolved with a drop in PASP to below 60 mmHg. Their new average was 36 mmHg, which was a drop of close to 50% from baseline values. The one-year survival of this sample was 100%. CONCLUSION: VAD implantation can reduce PAH levels. Early reduction occurred in all patients. Thus, use of VAD is an important bridge tool for enabling candidature for HT among patients with constantly severe PAH.

Plasma biomarkers reflecting high oxidative stress in the prediction of myocardial injury due to anthracycline chemotherapy and the effect of carvedilol: insights from the CECCY Trial.

BACKGROUND: Anthracycline (ANT) is often used for breast cancer treatment but its clinical use is limited by cardiotoxicity (CTX). CECCY trial demonstrated that the ß-blocker carvedilol (CVD) could attenuate myocardial injury secondary to ANT. Mieloperoxydase (MPO) is a biomarker of oxidative stress and galectin-3 (Gal-3) is a biomarker of fibrosis and cardiac remodeling. We evaluated the correlation between MPO and Gal-3 behavior with CTX. MATERIALS AND METHODS: A post hoc analysis was performed in the patients who were included in the CECCY trial. A total of 192 women had her blood samples stored during the study at -80°C until the time of assay in a single batch. Stored blood samples were obtained at baseline, 3 and 6 months after randomization. We excluded samples from 18 patients because of hemolysis. MPO and Gal-3 were measured using Luminex xMAP technology through MILLIPLEX MAP KIT (Merck Laboratories). RESULTS: 26 patients (14.9%) had a decrease of at least 10% in LVEF at 6 months after the initiation of chemotherapy. Among these, there was no significant difference in the MPO and Gal-3 when compared to the group without drop in LVEF (p = 0.85 for both MPO and Gal-3). Blood levels of MPO [baseline: 13.2 (7.9, 24.8), 3 months: 17.7 (11.1, 31.1), 6 months: 19.2 (11.1, 37.8) ng/mL] and Gal-3 [baseline: 6.3 (5.2, 9.6), 3 months: 12.3 (9.8, 16.0), 6 months: 10.3 (8.2, 13.1) ng/mL] increased after ANT chemotherapy, and the longitudinal changes were similar between the placebo and CVD groups (p for interaction: 0.28 and 0.32, respectively). In an exploratory analysis, as there is no normal cutoff value established for Gal-3 and MPO in the literature, the MPO and Gal-3 results were splited in two groups: above and below median. In the placebo group, women with high (above median) baseline MPO blood levels demonstrated a greater increase in TnI blood levels than those with low baseline MPO blood levels (p = 0.041). Compared with placebo, CVD significantly reduced TnI blood levels in women with high MPO blood levels (p < 0.001), but did not reduce the TnI levels in women with low baseline MPO blood levels (p = 0.97; p for interaction = 0.009). There was no significant interaction between CVD treatment and baseline Gal-3 blood levels (p for interaction = 0.99). CONCLUSIONS: In this subanalysis of the CECCY trial, MPO and Gal-3 biomarkers did not predict the development of CTX. However, MPO blood levels above median was associated with more severe myocardial injury and identified women who were most likely to benefit from carvedilol for primary prevention (NCT01724450).

Prevention and Treatment of Chemotherapy-Induced Cardiotoxicity.

Recent decades have seen an increase in survival rates for cancer patients, partially explained by earlier diagnoses and new chemotherapeutic agents. However, chemotherapy may be associated with adverse cardiovascular events, including hypertension and pulmonary hypertension, supraventricular and ventricular arrhythmias, cardiomyopathy, and other forms of cardiovascular disease. For patients, the benefits of chemotherapy may be partially obfuscated by deleterious effects on the cardiovascular system, resulting in a significant increase in morbidity and mortality. In this article, we review strategies for prevention and treatment of chemotherapy-related cardiotoxicity.

Antagonistas do Sistema Renina-Angiotensina e Betabloqueadores na Prevenção da Cardiotoxicidade por Antraciclinas: Revisão Sistemática e Metanálise / Renin-angiotensin System Antagonists and Beta-blockers in Prevention of Anthracycline Cardiotoxicity: a Systematic Review and Meta-analysis

Resumo Fundamento As evidências que embasam o uso de inibidores do sistema-renina-angiotensina aldosterona (SRAA) e betabloqueadores para prevenção de cardiomiopatia induzida por antraciclinas são controversas. Objetivo Realizamos uma metanálise para avaliar a eficácia desses medicamentos na prevenção da cardiotoxicidade. Métodos A metanálise incluiu estudos prospectivos e randomizados com adultos submetidos à quimioterapia com antraciclina e comparou o uso de terapias SRAA ou betabloqueadores versus placebo com seguimento de 6 a 18 meses. O desfecho primário foi alteração da fração de ejeção do ventrículo esquerdo (FEVE) durante a quimioterapia. Os desfechos secundários foram: a incidência de insuficiência cardíaca, mortalidade por todas as causas e alterações na medida do diâmetro diastólico final. A avaliação da heterogeneidade foi realizada por estratificação e meta-regressão. O nível de significância adotado foi p < 0,05. Resultados A busca resultou em 17 estudos, totalizando 1.530 pacientes. A variação (delta) da FEVE foi avaliada em 14 estudos. A terapia neuro-hormonal foi associada a um menor delta na FEVE pré-terapia versus pós-terapia (diferença média ponderada 4,42 [intervalo de confiança de 95% 2,3 a 6,6]) e maior FEVE final (p < 0,001). O tratamento resultou em menor incidência de insuficiência cardíaca (risk ratio 0,45 [intervalo de confiança de 95% 0,3 a 0,7]). Não houve efeito na mortalidade (p = 0,3). Para a análise da FEVE, foi documentada heterogeneidade substancial, não explicada pelas variáveis exploradas no estudo. Conclusão O uso de inibidores do SRAA e betabloqueadores para prevenção da cardiotoxicidade induzida por antraciclinas foi associado a redução menos pronunciada da FEVE, maior FEVE final e menor incidência de insuficiência cardíaca. Não foram observadas alterações na mortalidade. (CRD PROSPERO 42019133615)

Abstract Background The evidence supporting the use of renin-angiotensin-aldosterone system (RAAS) inhibitors and beta-blockers for the prevention of anthracycline-induced cardiomyopathy is controversial. Objective We performed a meta-analysis to assess the effectiveness of these drugs in preventing cardiotoxicity. Methods The meta-analysis included prospective, randomized studies in adults receiving anthracycline chemotherapy and compared the use of RAAS inhibitors or beta-blockers versus placebo with a follow-up of 6 to 18 months. The primary outcome was change in left ventricular ejection fraction (LVEF) during chemotherapy. Secondary outcomes were the incidence of heart failure, all-cause mortality, and changes in end-diastolic measurement. Heterogeneity was assessed by stratification and meta-regression. A significance level of p < 0.05 was adopted. Results The search resulted in 17 studies, totaling 1,530 patients. The variation (delta) in LVEF was evaluated in 14 studies. Neurohormonal therapy was associated with a lower delta in pre- versus post-therapy LVEF (weighted mean difference 4.42 [95% confidence interval 2.3 to 6.6]) and higher final LVEF (p < 0.001). Treatment resulted in a lower incidence of heart failure (risk ratio 0.45 [95% confidence interval 0.3 to 0.7]). There was no effect on mortality (p = 0.3). For analysis of LVEF, substantial heterogeneity was documented, which was not explained by the variables explored in the study. Conclusion The use of RAAS inhibitors and beta-blockers to prevent anthracycline-induced cardiotoxicity was associated with less pronounced reduction in LVEF, higher final LVEF, and lower incidence of heart failure. No changes in mortality were observed. (CRD PROSPERO 42019133615)

Carvedilol for Prevention of Chemotherapy-Related Cardiotoxicity: The CECCY Trial.

BACKGROUND: Anthracycline (ANT) chemotherapy is associated with cardiotoxicity. Prevention with ß-blockers remains controversial. OBJECTIVES: This prospective, randomized, double-blind, placebo-controlled study sought to evaluate the role of carvedilol in preventing ANT cardiotoxicity. METHODS: The authors randomized 200 patients with HER2-negative breast cancer tumor status and normal left ventricular ejection fraction (LVEF) referred for ANT (240 mg/m2) to receive carvedilol or placebo until chemotherapy completion. The primary endpoint was prevention of a ≥10% reduction in LVEF at 6 months. Secondary outcomes were effects of carvedilol on troponin I, B-type natriuretic peptide, and diastolic dysfunction. RESULTS: Primary endpoint occurred in 14 patients (14.5%) in the carvedilol group and 13 patients (13.5%) in the placebo group (p = 1.0). No differences in changes of LVEF or B-type natriuretic peptide were noted between groups. A significant difference existed between groups in troponin I levels over time, with lower levels in the carvedilol group (p = 0.003). Additionally, a lower incidence of diastolic dysfunction was noted in the carvedilol group (p = 0.039). A nonsignificant trend toward a less-pronounced increase in LV end-diastolic diameter during the follow-up was noted in the carvedilol group (44.1 ± 3.64 mm to 45.2 ± 3.2 mm vs. 44.9 ± 3.6 mm to 46.4 ± 4.0 mm; p = 0.057). CONCLUSIONS: In this largest clinical trial of ß-blockers for prevention of cardiotoxicity under contemporary ANT dosage, the authors noted a 13.5% to 14.5% incidence of cardiotoxicity. In this scenario, carvedilol had no impact on the incidence of early onset of LVEF reduction. However, the use of carvedilol resulted in a significant reduction in troponin levels and diastolic dysfunction. (Carvedilol Effect in Preventing Chemotherapy-Induced Cardiotoxicity [CECCY]; NCT01724450).

Early reduction of pulmonary arterial hypertension in patients using a long-term mechanical ventricular assistance device: a cross-sectional study

ABSTRACT BACKGROUND: Severe pulmonary arterial hypertension (PAH) is a contraindication for heart transplantation (HT). It has been correlated with increased early and late mortality, mainly associated with right ventricular failure. Ventricular assistance devices (VADs) can promote reduction of intracardiac pressures and consequent reduction of PAH over the medium and long terms, thus enabling future candidature for HT. The diminution of early pulmonary pressure within this scenario remains unclear. OBJECTIVE: To evaluate the reduction of PAH and correlate data from right catheterization with the earliness of this reduction. DESIGN AND SETTING: Cross-sectional study in a general hospital in São Paulo, Brazil. METHODS: This was a retrospective analysis on the medical records of patients undergoing VAD implantation in a single hospital. Patients for whom VAD had been indicated as a bridge to candidature for HT due to their condition of constant PAH were selected. RESULTS: Four patients with VADs had constantly severe PAH. Their mean pulmonary artery systolic pressure (PASP) before VAD implantation was 66 mmHg. Over the 30-day period after the procedure, all the patients evolved with a drop in PASP to below 60 mmHg. Their new average was 36 mmHg, which was a drop of close to 50% from baseline values. The one-year survival of this sample was 100%. CONCLUSION: VAD implantation can reduce PAH levels. Early reduction occurred in all patients. Thus, use of VAD is an important bridge tool for enabling candidature for HT among patients with constantly severe PAH.

Strain longitudinal global como preditor de cardiotoxicidade induzida por quimioterapia / Global longitudinal strain as predictor of chemotherapy-induced cardiotoxicity

Fundamento: A cardiotoxicidade induzida por quimioterapia (CiC) é uma complicação importante entre os pacientes que recebem antraciclinas. Biomarcadores e parâmetros de imagem têm sido estudados por sua capacidade de identificar pacientes com risco de desenvolver essa complicação. O strain longitudinal global do ventrículo esquerdo (SLG-VE) tem sido descrito como um parâmetro sensível para detectar disfunção sistólica, mesmo na presença de fração de ejeção do ventrículo esquerdo (FEVE) preservada. Objetivo: avaliar o papel do SLG-VE como preditor de CiC. Métodos: O presente estudo consiste em uma análise post-hoc do estudo CECCY (Carvedilol for Prevention of ChemotherapyRelated Cardiotoxicity [Carvedilol para Prevenção da Cardiotoxicidade Relacionada à Quimioterapia]), que avaliou a prevenção primária de cardiotoxicidade com carvedilol durante quimioterapia com doxorrubicina em uma população com câncer de mama. Definiu-se cardiotoxicidade como uma redução >10% na FEVE. O SLG-VE foi obtido antes da quimioterapia em pacientes sem doença cardiovascular prévia ou anormalidades no ecocardiograma. Resultados: Trinta e um pacientes submetidos a estudo ecocardiográfico completo incluindo avaliação de SLG-VE antes da quimioterapia foram incluídos nesta análise. Um SLG-VE absoluto <16,9% antes da quimioterapia mostrou 100% de sensibilidade e 73% de especificidade para predizer cardiotoxicidade (AUC=0,85; IC 95% 0,680­0,959, p<0,001). Nesta população, os valores de FEVE antes da quimioterapia não foram preditores de CiC (IC 95% 0,478 a -0,842, p=0,17). A associação de baixos níveis séricos de SLG-VE (<17%) e BNP (>17 pg/mL) dois meses após a quimioterapia aumentou a precisão para detectar CiC de início precoce (100% de sensibilidade, 88% de especificidade, AUC=0,94; IC 95% 0,7810,995, p<0,0001). Conclusões: Nossos dados sugerem que o SLG-VE é um possível preditor de cardiotoxicidade induzida por quimioterapia. São necessários estudos maiores para confirmar a relevância clínica desse parâmetro ecocardiográfico nesse cenário clínico. (AU)

Background: Chemotherapy-induced cardiotoxicity (ChC) is an important complication among patients receiving anthracyclines. Biomarkers and imaging parameters have been studied for their ability to identify patients at risk of developing ChC. Left ventricular global longitudinal strain (LV-GLS) is a sensitive parameter for detecting systolic dysfunction despite the presence of preserved left ventricular ejection fraction (LVEF). Objective: To evaluate the role of the LV-GLS as a predictor of ChC. Methods: This was a post-hoc analysis of the Carvedilol for Prevention of Chemotherapy-Related Cardiotoxicity trial, which evaluated the primary prevention of cardiotoxicity with carvedilol during doxorubicin chemotherapy in a population of patients with breast cancer. Cardiotoxicity was defined as a reduction ≥10% in LVEF. LV-GLS was determined before chemotherapy in patients with no prior cardiovascular disease or echocardiogram abnormalities. Results: Thirty-one patients for whom a complete echocardiography study including measurement of LV-GLS was performed before chemotherapy were included in this analysis. An absolute LV-GLS<16.9% before chemotherapy showed 100% sensitivity and 73% specificity for predicting cardiotoxicity (area under the curve [AUC], 0.85; 95% confidence interval [CI], 0.680­0.959; p<0.001). In this population, LVEF values before chemotherapy did not predict ChC (95% CI, 0.478 to -0.842; p=0.17). The association of low LV-GLS (<17%) and brain-type natriuretic peptide serum levels (>17 pg/mL) at 2 months after chemotherapy increased the accuracy for detecting early-onset ChC (100% sensitivity, 88% specificity; AUC, 0.94; 95% CI, 0.781­0.995; p<0.0001). Conclusions: Our data suggest that LV-GLS is a potential predictor of ChC. Larger studies are needed to confirm its clinical relevance in this clinical setting. (AU)

Avaliação de uma coorte de transplante cardíaco por escore relacionado ao doador / Assessment of a heart transplantation cohort using a donor-related scoring system

Existem poucos sistemas de avaliação de mortalidade após transplante cardíaco (TC) que se baseiem em fatores relacionados com o doador e que sejam capazes de predizer o prognóstico. Identificar características dos doadores que têm impacto na sobrevida depois do TC pode contribuir para melhorar os resultados e a alocação de órgãos. Aplicamos um sistema de avaliação americano para predizer a mortalidade pós-TC em uma coorte brasileira. Objetivo: Avaliar um escore americano como preditor de mortalidade depois de TC em uma coorte brasileira. Métodos: Análise de uma base de dados de um centro de TC brasileiro de 2013 a 2015. Foram avaliadas quatro características dos doadores: tempo de isquemia, idade do doador, discordância racial doador/receptor e a função renal do doador. A sobrevida foi estimada pelo teste de log-rank em faixas de pontuação pré-determinadas. Resultados: Foram 110 doadores, 89% homens e 62% brancos. A principal causa de morte foi trauma (66,6%). Os doadores tinham em média 29,8 anos, 18,6 de relação Nitrogênio da ureia sanguínea / Creatinina, 175 minutos de tempo de isquemia e 42% de discordância racial com o receptor. Não houve diferença de sobrevida entre as faixas de pontuação. Conclusão: Apesar de preditor de mortalidade após transplante cardíaco em uma população americana, esse escore não foi útil para uma coorte de transplante brasileira. As diferenças, inclusive a alta taxa de miscigenação pode ser uma explicação para esses achados

here are few systems to assess mortality after heart transplantation (CT) that are based on donor-related factors and can predict prognosis. Identifying donor characteristics that impact post-CT survival can contribute to improved outcomes and organ allocation. We applied a US evaluation system to predict mortality after CT in a Brazilian cohort. Objective: To evaluate an American score as a predictor of mortality following CT in a Brazilian cohort. Method: Database analysis of a Brazilian CT center from 2013 to 2015. Four donor characteristics were evaluated: ischemia time, donor age, donor-recipient race mismatch, and donor renal function. Survival was estimated by the log-rank test in predetermined score ranges. Results: There were 110 donors, 89% male and 62% white. The main cause of death was trauma (66.6%). Donors had a mean age of 29.8 years, a mean blood urea nitrogen / creatinine ratio of 18.6, a mean ischemia time of 175 minutes, and race mismatch with the recipient of 42%. There was no difference in survival between the score ranges. Conclusion: Although it was a predictor of mortality after cardiac transplantation in an American population, this score was not useful for a Brazilian transplant cohort. Differences, including the high rate of miscegenation, may explain these findings