Eustachian Valve Endocarditis in a Patient With Charcot-Marie-Tooth Disease.

Endocarditis is a serious infectious disease of the endocardial surface of the heart, predominantly involving the heart valves, and it results from the colonization and proliferation of microorganisms within the bloodstream. The condition primarily affects individuals with underlying cardiac abnormalities or those who have undergone invasive procedures. Symptoms may include pyrexia, fatigue, arthralgia, and new cardiac murmur. We present a case of a young male patient who had recently undergone surgery and developed eustachian valve endocarditis (EVE), a condition scarcely described in the literature.

Efficacy and safety of cardioprotective drugs in chemotherapy-induced cardiotoxicity: an updated systematic review & network meta-analysis.

BACKGROUND: Cancer patients receiving chemotherapy have an increased risk of cardiovascular complications. This limits the widespread use of lifesaving therapies, often necessitating alternate lower efficacy regimens, or precluding chemotherapy entirely. Prior studies have suggested that using common cardioprotective agents may attenuate chemotherapy-induced cardiotoxicity. However, small sample sizes and conflicting outcomes have limited the clinical significance of these results. HYPOTHESIS: A comprehensive network meta-analysis using updated and high-quality data can provide more conclusive information to assess which drug or drug class has the most significant effect in the management of chemotherapy-induced cardiotoxicity. METHODS: We performed a literature search for randomized controlled trials (RCTs) investigating the effects of cardioprotective agents in patients with chemotherapy-induced cardiotoxicity. We used established analytical tools (netmeta package in RStudio) and data extraction formats to analyze the outcome data. To obviate systematic bias in the selection and interpretation of RCTs, we employed the validated Cochrane risk-of-bias tools. Agents included were statins, aldosterone receptor antagonists (MRAs), ACEIs, ARBs, and beta-blockers. Outcomes examined were improvement in clinical and laboratory parameters of cardiac function including a decreased reduction in left ventricular ejection fraction (LVEF), clinical HF, troponin-I, and B-natriuretic peptide levels. RESULTS: Our study included 33 RCTs including a total of 3,285 patients. Compared to control groups, spironolactone therapy was associated with the greatest LVEF improvement (Mean difference (MD) = 12.80, [7.90; 17.70]), followed by enalapril (MD = 7.62, [5.31; 9.94]), nebivolol (MD = 7.30, [2.39; 12.21]), and statins (MD = 6.72, [3.58; 9.85]). Spironolactone was also associated with a significant reduction in troponin elevation (MD = - 0.01, [- 0.02; - 0.01]). Enalapril demonstrated the greatest BNP reduction (MD = - 49.00, [- 68.89; - 29.11]), which was followed by spironolactone (MD = - 16.00, [- 23.9; - 8.10]). Additionally, patients on enalapril had the lowest risk of developing clinical HF compared to the control population (RR = 0.05, [0.00; 0.75]). CONCLUSION: Our analysis reaffirmed that statins, MRAs, ACEIs, and beta-blockers can significantly attenuate chemotherapy-induced cardiotoxicity, while ARBs showed no significant effects. Spironolactone showed the most robust improvement of LVEF, which best supports its use among this population. Our analysis warrants future clinical studies examining the cardioprotective effects of cardiac remodeling therapy in cancer patients treated with chemotherapeutic agents.

Cardiotoxicity risk factors with immune checkpoint inhibitors.

BACKGROUND: Checkpoint-inhibitor immunotherapies have had a profound effect in the treatment of cancer by inhibiting down-regulation of T-cell response to malignancy. The cardiotoxic potential of these agents was first described in murine models and, more recently, in numerous clinical case reports of pericarditis, myocarditis, pericardial effusion, cardiomyopathy, and new arrhythmias. The objective of our study was to determine the frequency of and associated risk factors for cardiotoxic events in patients treated with immune checkpoint inhibitors. METHODS: Medical records of patients who underwent immunotherapy with durvalumab, ipilimumab, nivolumab, and pembrolizumab at Wake Forest Baptist Health were reviewed. We collected retrospective data regarding sex, cancer type, age, and cardiovascular disease risk factors and medications. We aimed to identify new diagnoses of heart failure, atrial fibrillation, ventricular fibrillation/tachycardia, myocarditis, and pericarditis after therapy onset. To assess the relationship between CVD risk factors and the number of cardiac events, a multivariate model was applied using generalized linear regression. Incidence rate ratios were calculated for every covariate along with the adjusted P-value. We applied a multivariate model using logistic regression to assess the relationship between CVD risk factors and mortality. Odds ratios were calculated for every covariate along with the adjusted P-value. Adjusted P-values were calculated using multivariable regression adjusting for other covariates. RESULTS: Review of 538 medical records revealed the following events: 3 ventricular fibrillation/tachycardia, 12 pericarditis, 11 atrial fibrillation with rapid ventricular rate, 0 myocarditis, 8 heart failure. Significant risk factors included female gender, African American race, and tobacco use with IRR 3.34 (95% CI 1.421, 7.849; P = 0.006), IRR 3.39 (95% CI 1.141, 10.055; P = 0.028), and IRR 4.21 (95% CI 1.289, 13.763; P = 0.017) respectively. CONCLUSIONS: Our study revealed 34 significant events, most frequent being pericarditis (2.2%) and atrial fibrillation (2.0%) with strongest risk factors being female gender, African American race, and tobacco use. Patients who meet this demographic, particularly those with planned pembrolizumab treatment, may benefit from early referral to a cardio-oncologist. Further investigation is warranted on the relationship between CTLA-4 and PD-L1 expression and cardiac adverse events with ICIs, particularly for these subpopulations.

NY-ESO-1 Vaccination in Combination with Decitabine Induces Antigen-Specific T-lymphocyte Responses in Patients with Myelodysplastic Syndrome.

Purpose: Treatment options are limited for patients with high-risk myelodysplastic syndrome (MDS). The azanucleosides, azacitidine and decitabine, are first-line therapy for MDS that induce promoter demethylation and gene expression of the highly immunogenic tumor antigen NY-ESO-1. We demonstrated that patients with acute myeloid leukemia (AML) receiving decitabine exhibit induction of NY-ESO-1 expression in circulating blasts. We hypothesized that vaccinating against NY-ESO-1 in patients with MDS receiving decitabine would capitalize upon induced NY-ESO-1 expression in malignant myeloid cells to provoke an NY-ESO-1-specific MDS-directed cytotoxic T-cell immune response.Experimental Design: In a phase I study, 9 patients with MDS received an HLA-unrestricted NY-ESO-1 vaccine (CDX-1401 + poly-ICLC) in a nonoverlapping schedule every four weeks with standard-dose decitabine.Results: Analysis of samples serially obtained from the 7 patients who reached the end of the study demonstrated induction of NY-ESO-1 expression in 7 of 7 patients and NY-ESO-1-specific CD4+ and CD8+ T-lymphocyte responses in 6 of 7 and 4 of 7 of the vaccinated patients, respectively. Myeloid cells expressing NY-ESO-1, isolated from a patient at different time points during decitabine therapy, were capable of activating a cytotoxic response from autologous NY-ESO-1-specific T lymphocytes. Vaccine responses were associated with a detectable population of CD141Hi conventional dendritic cells, which are critical for the uptake of NY-ESO-1 vaccine and have a recognized role in antitumor immune responses.Conclusions: These data indicate that vaccination against induced NY-ESO-1 expression can produce an antigen-specific immune response in a relatively nonimmunogenic myeloid cancer and highlight the potential for induced antigen-directed immunotherapy in a group of patients with limited options. Clin Cancer Res; 24(5); 1019-29. ©2017 AACRSee related commentary by Fuchs, p. 991.

Epigenetics: A primer for clinicians.

With recent advances in cellular biology, we now appreciate that modifications to DNA and histones can have a profound impact on transcription and function, even in the absence of changes to DNA sequence. These modifications, now commonly referred to as "epigenetic" alterations, have changed how we understand cell behavior, reprogramming and differentiation and have provided significant insight into the mechanisms underlying carcinogenesis. Epigenetic alterations, to this point, are largely identified by changes in DNA methylation and hydroxymethylation as well as methylation, acetylation, and phosphorylation of histone tails. These modifications enable significant flexibility in gene expression, rather than just turning genes "ON" or "OFF." Herein we describe the epigenetic landscape in the regulation of gene expression with a particular focus on interrogating DNA methylation in myeloid malignancy.