Successful Treatment of Steroid-Refractory Checkpoint Inhibitor Myocarditis with Globulin Derived-Therapy: A Case Report and Literature Review.

Immune checkpoint inhibitor (ICI) monoclonal antibody drugs are an important interface of immunology and cancer biology with the intended goal to create cancer specific treatments with less systemic toxicity. Recognition of immune-related adverse events is critical and these include significant cardiovascular toxicity and myocarditis. Compared with other immune-related events, ICI associated myocarditis is rare but is associated with high mortality. The majority of cases present early in the course of therapy and patients can rapidly progress to fulminant myocarditis. Initially, the mainstay of treatment in patients with ICI-associated myocarditis is immunosuppressive therapy with glucocorticoids. For those who do not respond to steroids, the optimal treatment is unclear. This review summarizes the potential adjunctive treatment options for patients with steroid-refractory myocarditis by illustrating a case of myocarditis that was treated with Thymoglobulin and immunoglobulin.

Machine learning helps predict long-term mortality and graft failure in patients undergoing heart transplant.

OBJECTIVE: We aimed to develop a risk prediction model using a machine learning to predict survival and graft failure (GF) 5 years after orthotopic heart transplant (OHT). METHODS: Using the International Society of Heart and Lung Transplant (ISHLT) registry data, we analyzed 15,236 patients who underwent OHT from January 2005 to December 2009. 342 variables were extracted and used to develop a risk prediction model utilizing a gradient-boosted machine (GBM) model to predict the risk of GF and mortality 5 years after hospital discharge. After excluding variables missing at least 50% of the observations and variables with near zero variance, 87 variables were included in the GBM model. Ten fold cross-validation repeated 5 times was used to estimate the model's external performance and optimize the hyperparameters simultaneously. Area under the receiver operator characteristic curve (AUC) for the GBM model was calculated for survival and GF 5 years post-OHT. RESULTS: The median duration of follow-up was 5 years. The mortality and GF 5 years post-OHT were 27.3% (n = 4161) and 28.1% (n = 4276), respectively. The AUC to predict 5-year mortality and GF is 0.717 (95% CI 0.696-0.737) and 0.716 (95% CI 0.696-0.736), respectively. Length of stay, recipient and donor age, recipient and donor body mass index, and ischemic time had the highest relative influence in predicting 5-year mortality and graft failure. CONCLUSION: The GBM model has a good accuracy to predict 5-year mortality and graft failure post-OHT.

Adriamycin-associated cardiomyopathy: where are we now? updates in pathophysiology, dose recommendations, prognosis, and outcomes.

PURPOSE OF REVIEW: Advances in cancer treatments have resulted in significant improvements in survival. Anthracycline chemotherapeutics play a major role in the treatment of hematologic malignancies and solid tumors; however, there is a risk of anthracycline cardiomyopathy in survivors. This focused review will provide a historical context on anthracycline cardiomyopathy and will also review pathophysiologic mechanisms of cardiotoxicity, dosage recommendations, prognosis, and outcomes. RECENT FINDINGS: Anthracycline inhibition of topoisomerase 2ß in cardiomyocytes is believed to be the dominant mechanism of anthracycline-related cardiotoxicity. Emerging data suggest that downregulation of the RNA-binding protein quaking 5 may also be contributing. There is continued lack of agreement regarding what dosage of anthracycline is associated with the highest risk of cardiotoxicity. SUMMARY: Ongoing research into the mechanisms of anthracycline cardiotoxicity is warranted to allow for the development of targeted preventive therapies. A consensus definition of anthracycline cardiomyopathy will facilitate analyses of existing data and allow for the conduction of prospective clinical trials in this area.

Chylopericardium following orthotopic lung transplantation.

Chylopericardium is an uncommon condition, reported to occur following routine cardiac surgery, orthotopic heart transplantation, cardiac trauma, intrathoracic tumors, or infection. It has not, to date, been reported following uncomplicated orthotopic lung transplantation. This article describes chylopericardium following bilateral orthotopic lung transplantation.

Characteristics and survival of patients with chemotherapy-induced cardiomyopathy undergoing heart transplantation.

BACKGROUND: New anti-neoplastic drugs have improved survival of cancer patients but have also been associated with chemotherapy-induced cardiomyopathy (CCMP), ultimately requiring orthotopic heart transplantation (OHT). We conducted this study to describe the clinical characteristics and outcomes of patients with CCMP treated with OHT and compare them with outcomes of patients with other forms of non-ischemic cardiomyopathy (NICMP). METHODS: We retrospectively identified 232 CCMP patients and 8,890 NICMP patients from the International Society of Heart and Lung Transplantation Registry who underwent OHT between January 2000 and December 2008. Survival rates were calculated using the Kaplan-Meier method. Categoric characteristics and outcomes groups were compared using the χ(2) and Fisher exact test. Comparisons for continuous variables were made using Wilcoxon-Mann-Whitney test. Multivariable analyses of predictors of survival were performed using Cox proportional hazard regression analysis. RESULTS: Short-term and long-term post-transplant survival of the 232 CCMP patients was similar to the 8,890 NICMP patients (p = 0.19). Survival (95% confidence interval) at 1, 3, and 5 years was, respectively, 86% (0.81-0.91), 79% (0.76-0.87), and 71% 0.73-0.85) in the CCMP patients and 87% (0.86-0.88), 81% (0.82-0.84), and 74% (0.80-0.81) in the NICMP patients (p = 0.19). Compared with NICMP patients, CCMP patients had higher rates of post-OHT infection (22% vs 14%, p = 004) and malignancies (5% vs 2%, p = 0.006), but neither affected survival. There was only 1 malignancy recurrence in the CCMP patients and no differences in post-OHT death due to malignancies between the groups. Importantly, CCMP patients were twice as likely as NICMP patients to require right ventricular assist devices before OHT (5.6% vs 2.3%, p = 0.0021). CONCLUSIONS: Patients with CCMP selected for OHT are younger, have less comorbidity, and are more likely to require biventricular mechanical support pre-OHT than other NICMP patients who receive allografts. Despite the higher incidence of malignancy and infection in CCMP patients who have received a heart transplant, their survival is comparable to those who receive allografts for other cardiomyopathies.