5-FU Cardiotoxicity: Vasospasm, Myocarditis, and Sudden Death.

PURPOSE OF REVIEW: 5-fluorouracil (5-FU) is one of the most common causes of cardiotoxicity associated with chemotherapy. The manifestations of 5-FU cardiotoxicity are diverse, and there are no established clinical guidelines addressing the diagnosis and management of this condition. Here we summarize the mechanistic and clinical data available to guide clinicians in caring for patients with suspected 5-FU cardiotoxicity. RECENT FINDINGS: The decision to resume 5-FU treatment in patients with suspected cardiovascular toxicity remains challenging. Testing for predisposing genetic variants may be helpful, particularly in patients with other signs of 5-FU toxicity. Uridine triacetate is a recently approved antidote that can improve clinical outcomes in patients with life-threatening fluoropyrimidine cardiotoxicity. 5-FU cardiotoxicity remains poorly understood, with limited mechanistic or prospective clinical trial data available to define risk factors or effective management strategies. Risk stratification and therapeutic decisions should be individualized, based on the risk-benefit ratio of continuing 5-FU therapy for each patient.

Zebrafish Models of Cancer Therapy-Induced Cardiovascular Toxicity.

PURPOSE OF REVIEW: Both traditional and novel cancer therapies can cause cardiovascular toxicity in patients. In vivo models integrating both cardiovascular and cancer phenotypes allow for the study of on- and off-target mechanisms of toxicity arising from these agents. The zebrafish is the optimal whole organism model to screen for cardiotoxicity in a high throughput manner, while simultaneously assessing the role of cardiotoxicity pathways on the cancer therapy's antitumor effect. Here we highlight established zebrafish models of human cardiovascular disease and cancer, the unique advantages of zebrafish to study mechanisms of cancer therapy-associated cardiovascular toxicity, and finally, important limitations to consider when using the zebrafish to study toxicity. RECENT FINDINGS: Cancer therapy-associated cardiovascular toxicities range from cardiomyopathy with traditional agents to arrhythmias and thrombotic complications associated with newer targeted therapies. The zebrafish can be used to identify novel therapeutic strategies that selectively protect the heart from cancer therapy without affecting antitumor activity. Advances in genome editing technology have enabled the creation of several transgenic zebrafish lines valuable to the study of cardiovascular and cancer pathophysiology. SUMMARY: The high degree of genetic conservation between zebrafish and humans, as well as the ability to recapitulate cardiotoxic phenotypes observed in patients with cancer, make the zebrafish an effective model to study cancer therapy-associated cardiovascular toxicity. Though this model provides several key benefits over existing in vitro and in vivo models, limitations of the zebrafish model include the early developmental stage required for most high-throughput applications.

Fluoropyrimidine-Associated Cardiotoxicity.

Fluoropyrimidines are chemotherapeutic agents that confer great benefit to many patients with solid tumors, but their use is often limited by cardiotoxicity. The incidence and precise mechanisms of cardiotoxicity remain uncertain. Clinical presentations of fluoropyrimidine toxicity are varied and include chest pain, myocardial infarction, acute cardiomyopathy, arrhythmia, cardiogenic shock, and sudden cardiac death. Proposed mechanisms include coronary vasospasm, coronary endothelial dysfunction, direct myocardial toxicity, myocarditis, and Takotsubo cardiomyopathy. Therapeutic and prophylactic interventions primarily target coronary vasospasm as the underlying cause. Prospective studies are needed to develop evidence-based approaches to cardioprotection in patients receiving fluoropyrimidines.

First catheter ablations in the Ministry of Health system of Peru: Report of the initial experience.

BACKGROUND: In 2015, the Ministry of Health (MINSA) of Peru inaugurated the first national center for electrophysiology studies in a public tertiary referral hospital with the purpose to provide healthcare access to the most underserved population. This study aims to describe the rate of success and complications of catheter ablation in this center since its inception, as well as the demographic characteristics of these patients. METHODS: This study is descriptive and retrospective. We used the medical record of the patients who underwent catheter ablation (first-time and re-do procedure) in the center from July 2015 to February 2018. RESULTS: 55 catheter ablations were performed in 53 patients, who were 35 (±15) years old and 47% male. 63.6% had a full MINSA health coverage, while 16.4% and 20% had partial MINSA coverage and no health coverage, respectively. Atrio-ventricular reentrant tachycardia mediated by accessory pathways was the most common (76.4%) electrophysiology diagnosis. The overall immediate success rate was 96.4%. No complications were reported. CONCLUSIONS: The efficacy and safety of this procedure are comparable to international standards. The main limitations might be the insufficiency of resources and inadequate diffusion of our center activity.