Background— Multiple studies have individually documented cardiac dysfunction and biochemical evidence of cardiac injury after endurance sports; however, convincing associations between the two are lacking. We aimed to determine the associations between the observed transient cardiac dysfunction and biochemical evidence of cardiac injury in amateur participants in endurance sports and to elicit the risk factors for the observed injury and dysfunction. Methods and Results— We screened 60 nonelite participants, before and after the 2004 and 2005 Boston Marathons, with echocardiography and serum biomarkers. Echocardiography included conventional measures as well as tissue Doppler–derived strain and strain rate imaging. Biomarkers included cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP). All subjects completed the race. Echocardiographic abnormalities after the race included altered diastolic filling, increased pulmonary pressures and right ventricular dimensions, and decreased right ventricular systolic function. At baseline, all had unmeasurable troponin. After the race, >60% of participants had increased cTnT >99th percentile of normal (>0.01 ng/mL), whereas 40% had a cTnT level at or above the decision limit for acute myocardial necrosis (≥0.03 ng/mL). After the race, NT-proBNP concentrations increased from 63 (interquartile range [IQR] 21 to 81) pg/mL to 131 (IQR 82 to 193) pg/mL ( P <0.001). The increase in biomarkers correlated with post-race diastolic dysfunction, increased pulmonary pressures, and right ventricular dysfunction (right ventricular mid strain, r =−0.70, P <0.001) and inversely with training mileage ( r =−0.71, P 45 miles/wk, athletes who trained ≤35 miles/wk demonstrated increased pulmonary pressures, right ventricular dysfunction (mid strain 16±5% versus 25±4%, P <0.001), myocyte injury (cTnT 0.09 versus <0.01 ng/mL, P <0.001), and stress (NT-proBNP 182 versus 106 pg/mL, P <0.001). Conclusions— Completion of a marathon is associated with correlative biochemical and echocardiographic evidence of cardiac dysfunction and injury, and this risk is increased in those participants with less training.

Purpose: The primary toxicity of trastuzumab therapy for human epidermal growth factor receptor 2–overexpressing (HER2-positive) breast cancer is dose-independent cardiac dysfunction. Angiotensin-converting enzyme inhibitors and β-blockers are recommended first-line agents for heart failure. We hypothesized that angiotensin-converting enzyme inhibitors and β-blockers could prevent trastuzumab-related cardiotoxicity. Patients and Methods: In this double-blinded, placebo-controlled trial, patients with HER2-positive early breast cancer were randomly assigned to receive treatment with perindopril, bisoprolol, or placebo (1:1:1) for the duration of trastuzumab adjuvant therapy. Patients underwent cardiac magnetic resonance imaging at baseline and post–cycle 17 for the determination of left ventricular volumes and left ventricular ejection fraction (LVEF). Cardiotoxicity was evaluated as the change in indexed left ventricular end diastolic volume and LVEF. Results: Thirty-three patients received perindopril, 31 received bisoprolol, and 30 received placebo. Baseline demographic, cancer, and cardiovascular profiles were similar between groups. Study drugs were well tolerated with no serious adverse events. After 17 cycles of trastuzumab, indexed left ventricular end diastolic volume increased in patients treated with perindopril (+7 ± 14 mL/m²), bisoprolol (+8 mL ± 9 mL/m²), and placebo (+4 ± 11 mL/m²; P = .36). In secondary analyses, trastuzumab-mediated decline in LVEF was attenuated in bisoprolol-treated patients (−1 ± 5%) relative to the perindopril (−3 ± 4%) and placebo (−5 ± 5%) groups ( P = .001). Perindopril and bisoprolol use were independent predictors of maintained LVEF on multivariable analysis. Conclusion: Perindopril and bisoprolol were well tolerated in patients with HER2-positive early breast cancer who received trastuzumab and protected against cancer therapy–related declines in LVEF; however, trastuzumab-mediated left ventricular remodeling—the primary outcome—was not prevented by these pharmacotherapies.

Cardiovascular disease in pregnancy is the leading cause of maternal mortality in North America. Although transthoracic echocardiography (TTE) is the most widely used imaging modality for the assessment of cardiovascular function during pregnancy, little is known on the role of cardiovascular magnetic resonance (CMR). The objective of the Cardiac Hemodynamic Imaging and Remodeling in Pregnancy (CHIRP) study was to compare TTE and CMR in the non-invasive assessment of maternal cardiac remodeling during the peripartum period.

Significance: We provide new, exciting evidence for a previously unidentified signaling pathway that mechanistically links mitochondrial respiratory chain defects to necrosis and heart failure induced by the chemotherapy agent doxorubicin (DOX). We specifically show that DOX disrupts protein complexes between the key respiratory chain proteins, including uncoupling protein 3 and cytochrome c oxidase, resulting in abnormal mitochondrial respiration and necrosis through a mechanism contingent on Bcl-2-like 19kDa-interacting protein 3 (Bnip3). Perhaps most compelling is our finding that inhibiting Bnip3 completely abrogated the cardiotoxic effects of DOX. These exciting findings have important clinical implications not only for preventing heart failure by targeting Bnip3 in cancer patients undergoing chemotherapy, but also for understanding the pathogenesis of other diseases in which mitochondrial function is compromised.