Critical appraisal of costly therapy modalities for heart failure in a developing country.

Contemporaneous challenges in heart failure management include strategies to rationally use health economic resources and relative donor shortage to adequately offer electric devices (cardiac resynchronization therapy [CRT] and implantable cardioverter defibrillators [ICD]), ventricular assist devices (VADs) and heart transplant, respectively. These issues are particularly important in countries with middle-income rates and limited structured heart transplant centers, such as Brazil. Use of CRT and ICDs need to follow strict guidelines, further customized to public financial health conditions. Experience with VADs in is the early days in Brazil and will require extreme caution to allocate health public resources to develop VAD programs in highly selected centers. Chagas' disease is epidemiologically important in Brazil; outcomes of patients with Chagas' on electric devices are unclear while these patients fare better post-transplant than non-Chagas' patients. Thus, heart transplant remains an attractive option regarding both favorable outcomes and resource allocation for advanced heart failure patients in Brazil.

The "Lightbulb" Sign: A Novel Echocardiographic Finding Using Ultrasound Enhancing Agent in Fulminant COVID-19-Related Myocarditis.

We report a case of fulminant COVID-19-related myocarditis requiring venoarterial extracorporeal membrane oxygenation where the use of an ultrasound-enhancing agent demonstrated a previously undescribed echocardiographic finding, the "lightbulb" sign. This sign potentially represents a new area for the use of an ultrasound enhancing agent in the echocardiographic diagnosis of myocarditis.

Dynamic Metabolic Changes During Prolonged Ex Situ Heart Perfusion Are Associated With Myocardial Functional Decline.

Ex situ heart perfusion (ESHP) was developed to preserve and evaluate donated hearts in a perfused beating state. However, myocardial function declines during ESHP, which limits the duration of perfusion and the potential to expand the donor pool. In this research, we combine a novel, minimally-invasive sampling approach with comparative global metabolite profiling to evaluate changes in the metabolomic patterns associated with declines in myocardial function during ESHP. Biocompatible solid-phase microextraction (SPME) microprobes serving as chemical biopsy were used to sample heart tissue and perfusate in a translational porcine ESHP model and a small cohort of clinical cases. In addition, six core-needle biopsies of the left ventricular wall were collected to compare the performance of our SPME sampling method against that of traditional tissue-collection. Our state-of-the-art metabolomics platform allowed us to identify a large number of significantly altered metabolites and lipid species that presented comparable profile of alterations to conventional biopsies. However, significant discrepancies in the pool of identified analytes using two sampling methods (SPME vs. biopsy) were also identified concerning mainly compounds susceptible to dynamic biotransformation and most likely being a result of low-invasive nature of SPME. Overall, our results revealed striking metabolic alterations during prolonged 8h-ESHP associated with uncontrolled inflammation not counterbalanced by resolution, endothelial injury, accelerated mitochondrial oxidative stress, the disruption of mitochondrial bioenergetics, and the accumulation of harmful lipid species. In conclusion, the combination of perfusion parameters and metabolomics can uncover various mechanisms of organ injury and recovery, which can help differentiate between donor hearts that are transplantable from those that should be discarded.

Mortality in patients with cardiogenic shock supported with VA ECMO: A systematic review and meta-analysis evaluating the impact of etiology on 29,289 patients.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (VA ECMO) is associated with variable outcomes. In this meta-analysis, we evaluated the mortality after VA ECMO across multiple etiologies of cardiogenic shock (CS). METHODS: In June 2019, we performed a systematic search selecting observational studies with ≥10 adult patients reporting on short-term mortality (30-day or mortality at discharge) after initiation of VA ECMO by CS etiology published after 2009. We performed meta-analyses using random effect models and used metaregression to evaluate mortality across CS etiology. RESULTS: We included 306 studies (29,289 patients): 25 studies on after heart transplantation (HTx) (771 patients), 13 on myocarditis (906 patients), 33 on decompensated heart failure (HF) (3,567 patients), 64 on after cardiotomy shock (8,231 patients), 10 on pulmonary embolism (PE) (221 patients), 80 on acute myocardial infarction (AMI) (7,774 patients), and 113 on after cardiac arrest [CA] (7,814 patients). With moderate certainty on effect estimates, we observed significantly different mortality estimates for various etiologies (p < 0.001), which is not explained by differences in age and sex across studies: 35% (95% CI: 29-42) for after HTx, 40% (95% CI: 33-46) for myocarditis, 53% (95% CI: 46-59) for HF, 52% (95% CI: 38-66) for PE, 59% (95% CI: 56-63) for cardiotomy, 60% (95% CI: 57-64) for AMI, 64% (95% CI: 59-69) for post‒in-hospital CA, and 76% (95% CI: 69-82) for post-out‒of-hospital CA. Univariable metaregression showed that variation in mortality estimates within etiology group was partially explained by population age, proportion of females, left ventricle venting, and CA. CONCLUSIONS: Using an overall estimate of mortality for patients with CS requiring VA ECMO is inadequate given the differential outcomes by etiology. To further refine patient selection and management to improve outcomes, additional studies evaluating patient characteristics impacting outcomes by specific CS etiology are needed.

Comparing Donor Heart Assessment Strategies During Ex Situ Heart Perfusion to Better Estimate Posttransplant Cardiac Function.

BACKGROUND: Ex situ heart perfusion (ESHP) limits ischemic periods and enables continuous monitoring of donated hearts; however, a validated assessment method to predict cardiac performance has yet to be established. We compare biventricular contractile and metabolic parameters measured during ESHP to determine the best evaluation strategy to estimate cardiac function following transplantation. METHODS: Donor pigs were assigned to undergo beating-heart donation (n = 9) or donation after circulatory death (n = 8) induced by hypoxia. Hearts were preserved for 4 hours with ESHP while invasive and noninvasive (NI) biventricular contractile, and metabolic assessments were performed. Following transplantation, hearts were evaluated at 3 hours of reperfusion. Spearman correlation was used to determine the relationship between ESHP parameters and posttransplant function. RESULTS: We performed 17 transplants; 14 successfully weaned from bypass (beating-heart donation versus donation after circulatory death; P = 0.580). Left ventricular invasive preload recruitable stroke work (PRSW) (r = 0.770; P = 0.009), NI PRSW (r = 0.730; P = 0.001), and NI maximum elastance (r = 0.706; P = 0.002) strongly correlated with cardiac index (CI) following transplantation. Right ventricular NI PRSW moderately correlated to CI following transplantation (r = 0.688; P = 0.003). Lactate levels were weakly correlated with CI following transplantation (r = -0.495; P = 0.043). None of the echocardiography measurements correlated with cardiac function following transplantation. CONCLUSIONS: Left ventricular functional parameters, especially ventricular work and reserve, provided the best estimation of myocardial performance following transplantation. Furthermore, simple NI estimates of ventricular function proved useful in this setting. Right ventricular and metabolic measurements were limited in their ability to correlate with myocardial recovery. This emphasizes the need for an ESHP platform capable of assessing myocardial contractility and suggests that metabolic parameters alone do not provide a reliable evaluation.

Redo sternotomy versus left ventricular assist device explant as risk factors for early mortality following heart transplantation.

OBJECTIVES: There is an increasing proportion of patients with a previous sternotomy (PS) or durable left ventricular assist device (LVAD) undergoing heart transplantation (HT). We hypothesized that patients with LVAD support at the time of HT have a lower risk than patients with PS and may have a comparable risk to patients with a virgin chest (VC). METHODS: This is a single-centre retrospective cohort study of all adults who underwent primary single-organ HT between 2002 and 2017. Multivariable Cox regression analyses were performed to compare 30-day and 1-year mortality between transplanted patients with a VC (VC-HT), a PS (PS-HT) or an LVAD explant (LVAD-HT). RESULTS: Three hundred seventy-nine patients were analysed (VC-HT: 196, PS-HT: 94, LVAD-HT: 89). A larger proportion of patients in the LVAD-HT group were males (83%), had blood group O (52%), non-ischaemic aetiology (70%) and sensitization (67%). The PS-HT group had a higher frequency of patients with congenital heart disease (30%) and PSs compared to LVAD-HT patients (P < 0.001). PS-HT and LVAD-HT patients required a longer bypass time (P < 0.001) and showed a greater estimated blood loss (P < 0.001). Postoperatively, LVAD-HT required haemodialysis more frequently than the VC-HT group (P = 0.031). Multivariable analyses found that PS-HT patients had increased 30-day mortality compared to VC-HT [hazard ratio (HR) 2.63, 95% confidence interval (CI) 1.15-6.01; P = 0.022] while LVAD-HT did not (HR 2.17, 95% CI 0.96-4.93; P = 0.064). At 1-year, neither PS-HT nor LVAD-HT groups were significantly associated with increased mortality compared to VC-HT. CONCLUSIONS: Transplants in recipients with PS-HT demonstrated increased early mortality compared to VC-HT patients. Although LVAD explant is often technically challenging, this population demonstrated similar mortality compared to those VC-HT patients. The chronic and perioperative support provided by the LVAD may play a favourable role in early patient outcomes compared to other redo sternotomy patients.

Comparison of Heart Transplantation Outcomes: Adult Congenital Heart Disease vs Matched Cardiac Patients in a Quaternary Reference Centre.

BACKGROUND: The number of transplantations performed for adult congenital heart disease (ACHD) patients is increasing. We sought to compare survival and post-transplantation complications, including graft failure, rejection, dialysis, and use of a right ventricular assist device, between ACHD and a cohort of dilated (DCM) and ischemic (ICM) cardiomyopathy patients matched by age and year of transplantation. METHODS: We retrospectively reviewed our single-institution heart transplantation database and selected all patients who had surgery from 1988 to 2017. In our primary analysis, we looked at survival and post-transplantation complications across cardiomyopathy groups. Our secondary analysis was matched to mitigate era effects as well as differences in age at transplant. RESULTS: We analyzed a cohort consisting of 303 heart transplant patients with cardiomyopathy due to either 1) ACHD (n = 38), 2) ICM (n = 110), or 3) DCM (n = 155). Kaplan-Meier analysis and a multivariable Cox proportional hazard regression model were used for all-cause mortality, and cause-specific hazard regression for cause-specific mortality and morbidity. There was no statistically significant survival difference across groups. The 1-year survival was 68.5% for ACHD, 85.4% for ICM, and 85.5% for DCM. In multivariable analysis, ICM and DCM patients showed a 66% lower risk of death relative to the ACHD group. The matched analysis showed no significant difference in survival across groups. CONCLUSIONS: ACHD patients represent a growing high-risk patient cohort referred for transplantation. To improve survival outcomes we need to address modifiable risk factors.

A Pre-Clinical Porcine Model of Orthotopic Heart Transplantation.

Fifty-years following the first successful report, cardiac transplantation remains the gold-standard treatment for eligible patients with advanced heart failure. Multiple small-animal models of heart transplantation have been used to study the acute and long-term effects of novel therapies. However, few are tested and demonstrated success in clinical trials. It is of critical importance to evaluate new therapies in a clinically relevant large-animal model for efficient and reliable translation of basic studies' findings. Here, we describe a pre-clinical large-animal (porcine) model of orthotopic heart transplantation that has been firmly established and previously used to investigate novel cardioprotective strategies. This procedure focuses on acute ischemia-reperfusion injury and is a reliable method to investigate novel interventions which have been tested and validated in smaller experimental models, such as the murine model. We demonstrate its usefulness in assessing cardiac performance during the early post-transplantation period and other potential possibilities enabled by the model.

Hearts Donated After Circulatory Death and Reconditioned Using Normothermic Regional Perfusion Can Be Successfully Transplanted Following an Extended Period of Static Storage.

BACKGROUND: There has been an increased interest in donation after circulatory death (DCD) to expand donor pool for cardiac transplantation. Normothermic regional perfusion (NRP) allows in situ assessment of DCD hearts, allowing only acceptable organs to be procured. We sought to determine if extended cold storage was possible for DCD hearts following NRP and to compare hearts stored using standard cold storage with a novel cardioprotective solution designed for room temperature storage. METHODS AND RESULTS: Donor pigs underwent hypoxic cardiac arrest (DCD) followed by 15 minutes of warm ischemia and resuscitation on NRP. They were then randomly assigned to static storage with histidine-tryptophan-ketoglutarate (HTK) at 4°C (HTK group, n=5) or SOM-TRN-001 at 21°C (SOM group, n=5). Conventional beating-heart donations were used as controls (n=4). Fourteen transplants were successfully performed. HTK hearts showed initial dysfunction following reperfusion; however, they demonstrated significant recovery up to 3 hours post-transplant. No significant differences were seen between HTK and control hearts post-transplantation (cardiac index: control 49.5±6% and HTK 48.5±5% of baseline). SOM improved myocardial preservation; hearts showed stable contractility after transplantation (cardiac index: 113.0±43% of NRP function) and improved diastolic function compared with HTK. Preservation in SOM also significantly reduced proinflammatory cytokine production and release following transplantation and partially prevented endothelial dysfunction. CONCLUSIONS: DCD hearts stored using a standard preservation solution demonstrated comparable post-transplantation myocardial function to standard controls. Thus, short periods of cold storage following successful NRP and documented adequate function is an acceptable strategy for DCD hearts. Preservation in SOM at room temperature is feasible and can improve cardiac recovery by minimizing endothelial dysfunction and tissue injury.

History of Cardiovascular Surgery at Toronto General Hospital.

The Division of Cardiovascular Surgery at Toronto General Hospital has enjoyed an enviable history of academic achievement and clinical success. The foundations of this success are innovation, creativity and excellence in patient care, which continue to influence the current members of the division.

Association between Spirituality and Adherence to Management in Outpatients with Heart Failure.

BACKGROUND: Spirituality may influence how patients cope with their illness. OBJECTIVES: We assessed whether spirituality may influence adherence to management of outpatients with heart failure. METHODS: Cross sectional study enrolling consecutive ambulatory heart failure patients in whom adherence to multidisciplinary treatment was evaluated. Patients were assessed for quality of life, depression, religiosity and spirituality utilizing validated questionnaires. Correlations between adherence and psychosocial variables of interest were obtained. Logistic regression models explored independent predictors of adherence. RESULTS: One hundred and thirty patients (age 60 ± 13 years; 67% male) were interviewed. Adequate adherence score was observed in 38.5% of the patients. Neither depression nor religiosity was correlated to adherence, when assessed separately. Interestingly, spirituality, when assessed by both total score sum (r = 0.26; p = 0.003) and by all specific domains, was positively correlated to adherence. Finally, the combination of spirituality, religiosity and personal beliefs was an independent predictor of adherence when adjusted for demographics, clinical characteristics and psychosocial instruments. CONCLUSION: Spirituality, religiosity and personal beliefs were the only variables consistently associated with compliance to medication in a cohort of outpatients with heart failure. Our data suggest that adequately addressing these aspects on patient's care may lead to an improvement in adherence patterns in the complex heart failure management.

Mediastinitis: mortality rate comparing single-stage surgical approach and preconditioning of wound.

OBJECTIVE: This study aims to compare hospital mortality rate of surgical debridement followed by primary wound closure versus surgical debridement with closure after preconditioning of the wound. METHODS: A historical cohort of 43 patients with postoperative mediastinitis type III and IV between 2000 and 2008. The diagnosis of mediastinitis was based on physical examination and laboratory tests. Patients were divided into two groups: patients who received the protocol of preconditioning of the wound (Group 2) and those who did not (Group 1). RESULTS: Of the 43 patients, 15 received the protocol and were assigned to Group 2, and 28 patients to Group 1. Myocardial revascularisation was the surgical intervention most affected by infection, accounting for 69.8% of patients in Group 1 and 64.3% in Group 2.Staphylococcus aureus was the predominant pathogen, accounting for 58.1% of all cases, 50% in Group 1 and 73.3% in Group 2. Hospital mortality rate was 42.9% in Group 1 and 20% in Group 2 (P=1.86), with relative risk of 2.14 and CI [0.714-6.043]. Among the 28 (65.1%) patients who underwent single-stage surgical approach, 12 (27.9%) underwent primary wound closure with irrigation, seven (16.3%) only primary closure, six (14%) omental flap, and three (7%) pectoralis muscle flap. CONCLUSION: Due to the lack of established guidelines, the choice of the surgical approach is based largely on low-level evidence references. Preconditioning of the wound appears to lead to a reduction in mortality in these patients, being a good surgical option.

Association between Spirituality and Adherence to Management in Outpatients with Heart Failure / Associação entre Espiritualidade e Adesão ao Tratamento em Pacientes Ambulatoriais com Insuficiência Cardíaca

Abstract Background: Spirituality may influence how patients cope with their illness. Objectives: We assessed whether spirituality may influence adherence to management of outpatients with heart failure. Methods: Cross sectional study enrolling consecutive ambulatory heart failure patients in whom adherence to multidisciplinary treatment was evaluated. Patients were assessed for quality of life, depression, religiosity and spirituality utilizing validated questionnaires. Correlations between adherence and psychosocial variables of interest were obtained. Logistic regression models explored independent predictors of adherence. Results: One hundred and thirty patients (age 60 ± 13 years; 67% male) were interviewed. Adequate adherence score was observed in 38.5% of the patients. Neither depression nor religiosity was correlated to adherence, when assessed separately. Interestingly, spirituality, when assessed by both total score sum (r = 0.26; p = 0.003) and by all specific domains, was positively correlated to adherence. Finally, the combination of spirituality, religiosity and personal beliefs was an independent predictor of adherence when adjusted for demographics, clinical characteristics and psychosocial instruments. Conclusion: Spirituality, religiosity and personal beliefs were the only variables consistently associated with compliance to medication in a cohort of outpatients with heart failure. Our data suggest that adequately addressing these aspects on patient’s care may lead to an improvement in adherence patterns in the complex heart failure management.

Resumo Fundamento: A espiritualidade pode influenciar a maneira com que os pacientes lidam com sua doença. Objetivos: Avaliamos a possibilidade de a espiritualidade influenciar a adesão ao tratamento de pacientes ambulatoriais com insuficiência cardíaca. Métodos: Estudo transversal com pacientes ambulatoriais com insuficiência cardíaca, cuja adesão ao tratamento multidisciplinar foi avaliada. Os pacientes foram avaliados sobre qualidade de vida, depressão, religiosidade e espiritualidade, utilizando questionários validados. Foram obtidas correlações entre adesão e variáveis psicossociais de interesse. Modelos de regressão logística exploraram preditores independentes de adesão. Resultados: Cento e trinta pacientes (idade 60 ± 13 anos; 67% masculinos) foram entrevistados. Observou-se adequado escore de adesão em 38,5% dos pacientes. Nem a depressão ou a religiosidade foram correlacionados à adesão, quando avaliados separadamente. É interessante notar que quando a espiritualidade foi avaliada por ambos, o somatório total de score (r = 0,26; p = 0,003) e os domínios específicos, ela estava positivamente correlacionada à adesão. Por fim, a combinação de espiritualidade, religiosidade e crenças pessoais mostrou-se um preditor independente de adesão quando ajustado às características demográficas, clínicas e a instrumentos psicossociais. Conclusão: Espiritualidade, religiosidade e crenças pessoais foram as únicas variáveis consistentemente associadas à adesão em relação à medicação em uma coorte de pacientes ambulatoriais com insuficiência cardíaca. Nossos dados sugerem que abordar adequadamente esses aspectos no cuidado com o paciente pode auxiliar a melhorar o padrão de adesão no complexo tratamento da insuficiência cardíaca.

Mediastinitis: mortality rate comparing single-stage surgical approach and preconditioning of wound / Mediastinite: mortalidade comparando abordagem cirúrgica em tempo único e o pré-condicionamento da ferida operatória

OBJECTIVE: This study aims to compare hospital mortality rate of surgical debridement followed by primary wound closure versus surgical debridement with closure after preconditioning of the wound. METHODS: A historical cohort of 43 patients with postoperative mediastinitis type III and IV between 2000 and 2008. The diagnosis of mediastinitis was based on physical examination and laboratory tests. Patients were divided into two groups: patients who received the protocol of preconditioning of the wound (Group 2) and those who did not (Group 1). RESULTS: Of the 43 patients, 15 received the protocol and were assigned to Group 2, and 28 patients to Group 1. Myocardial revascularisation was the surgical intervention most affected by infection, accounting for 69.8% of patients in Group 1 and 64.3% in Group 2.Staphylococcus aureus was the predominant pathogen, accounting for 58.1% of all cases, 50% in Group 1 and 73.3% in Group 2. Hospital mortality rate was 42.9% in Group 1 and 20% in Group 2 (P=1.86), with relative risk of 2.14 and CI [0.714-6.043]. Among the 28 (65.1%) patients who underwent single-stage surgical approach, 12 (27.9%) underwent primary wound closure with irrigation, seven (16.3%) only primary closure, six (14%) omental flap, and three (7%) pectoralis muscle flap. CONCLUSION: Due to the lack of established guidelines, the choice of the surgical approach is based largely on low-level evidence references. Preconditioning of the wound appears to lead to a reduction in mortality in these patients, being a good surgical option.

OBJETIVO: Este estudo tem por objetivo comparar a taxa de mortalidade intra-hospitalar do debridamento cirúrgico seguido de fechamento da ferida operatória, com a do debridamento cirúrgico com fechamento após pré-condicionamento da ferida. MÉTODOS: Coorte histórica composta por 43 pacientes portadores de mediastinite pós-operatória tipo III e IV entre os anos de 2000 e 2008. O diagnóstico de mediastinite foi feito com base em exames físico e laboratoriais. Os pacientes foram divididos em dois grupos, os que seguiram o protocolo de pré-condicionamento da ferida operatória (Grupo 2) ou não (Grupo 1). RESULTADOS: Dos 43 pacientes, 15 seguiram o protocolo e foram alocados no Grupo 2. A revascularização do miocárdio foi a cirurgia mais afetada pela infecção, sendo responsável por 69,8% dos pacientes no Grupo 1 e 64,3% no Grupo 2. O Staphylococcus aureus foi o germe mais prevalente, sendo responsável por 58,1% do total dos casos, sendo 50% e 73,3%, respectivamente, nos Grupos 1 e 2. A mortalidade intra-hospitalar foi de 42,9% no Grupo 1 e de 20% no Grupo 2 (P=1,86), com risco relativo de 2,14 e IC [0,714-6,043]. Entre os 28 (65,1%) pacientes do estudo que seguiram a abordagem cirúrgica em um único tempo, 12 (27,9%) foram submetidos a fechamento primário com irrigação, sete (16,3%), a fechamento primário isolado, seis (14%), rotação de retalho de epíplon, e três (7%), interposição de retalho de músculo peitoral. CONCLUSÃO: Na ausência de uma diretriz bem estabelecida, a escolha do tipo de intervenção cirúrgica é feita utilizando-se referências com baixo nível de evidência. O pré-condicionamento da ferida operatória parece levar a redução da mortalidade nesses pacientes, sendo uma boa alternativa cirúrgica.

Síndrome da artéria mesentérica superior / Superior mesenteric artery syndrome

Superior mesenteric artery syndrome is an uncommon and controversial disease. The diagnosis is based on clinical, radiographic, gastroscopic and ultrasound findings. A review of a case is presented, with discussion of the clinical findings and diagnosis. Surgical treatment in indicated on medical treatment failure. Duodenojejunostomy is associated with 90 per cent success rate