Anuj Shah

Fluoropyrimidine-associated cardiotoxicity: revisited

Background: The syndrome of 5-fluorouracil (5-FU)-associated cardiotoxicity remains poorly defined. Patients and methods: We performed a literature review (1969 – 2007) and compiled data derived from 377 evaluable cases out of 448 reported cases. Results: Patient age ranged from 14 to 86 years. Of the patients 65% were 55 years old and the male:female ratio was 1.5:1. The most commonly treated tumors were gastrointestinal (60%), head and neck (22%) and breast (4%). Of the patients 14% had a history of heart disease whereas cardiac risk factors were found in 37%. Mode of administration included: continuous infusion (72%); bolus (22.5%); intermediate infusion (3%); oral (2%); and intraperitoneal (1 patient). The dosages of 5-FU used were < 750 mg/m2/day (36%), 751 – 999 (16%), 1,000 (26%), 1,001 – 1,499 (4%) and 1,500 (16%). Of the patients 54% received 5-FU in combination with other chemotherapeutic agents (cisplatin 44%) whereas 51% received 5-FU alone or with leucovorin. Only 4% patients had undergone previous or concomitant radiation therapy to the mediastinum. Of cardiac incidents that happened 69% were seen during or within 72 h of the first cycle of 5-FU. Angina occurred in 45% of patients whereas myocardial infarction was seen in 22%, arrhythmias in 23, acute pulmonary edema in 5, cardiac arrest and pericarditis in 1.4 and heart failure in 2. Electro-cardiographic evidence of ischemia or ST-T changes were recorded in 69% of patients, but abnormal cardiac enzymes were found in only 12%. The cardiac symptoms were reproducible in 47%, including in one patient subsequently treated with 5-FU p.o. Symptoms were also elicited when the same patients were treated with lower doses or different schedules. Of the patients 68% responded to conservative anti-anginal therapy, although prophylactic coronary vasodilators had limited efficacy. Overall, 8% of patients showing cardiotoxicity on 5-FU administration died. Furthermore, 13% reexposed to 5-FU died. Conclusions: Our review suggests that 5-FU cardiotoxicity is an infrequent but real phenomenon that is independent of dose and may be related to a continuous infusion schedule. The presence of cardiac risk factors is not predictive. Patients should be observed closely and 5-FU administration discontinued if cardiac symptoms develop. A rechallenge with 5-FU should be reserved only for those patients in whom there is no reasonable alternative therapy and should be performed in the setting of aggressive prophylaxis and close monitoring.

Thermal mapping of right ventricular outflow tract tachycardia.

Background: Acute and long‐term success of catheter ablation of right ventricular outflow tract tachycardia (RVOT VT) may be limited by the inability to reproduce the arrhythmia at the time of activation (AM) and pace mapping (PM). We have observed early initiation of the clinical VT when subtherapeutic radiofrequency (RF) energy was applied to the target area (TA), defined as a 2‐cm2 area around a pace match. We describe a novel approach using thermal mapping (TM) to guide the ablation of RVOT VT.

Possible mechanisms for statin myopathy and its relationship to physical exercise

Statins are a very effective and well-tolerated class of lipid-lowering agents that have been shown to reduce the risk of first and recurrent cardiovascular events. Their major adverse side effect is that they can produce a variety of skeletal muscle complaints ranging from mild myalgia to life-threatening rhabdomyolysis. Exercise can also injure skeletal muscle, and many cases of presumed statin myopathy are associated with physical activity. This literature review summarizes current concepts of statin myopathy and discuses how physical exercise may both exacerbate symptoms and possibly assist in defining the mechanisms of statin-associated muscle injury. The results suggest that exercise may cause many of the creatine kinase (CK) elevations during statin therapy and also exacerbate these CK increases. Physicians should also consider, based on circumstantial evidence, withholding statins prior to prolonged vigorous exercise to avoid clinically important rhabdomyolysis.