Cardiac Magnetic Resonance Assessment of Interstitial Myocardial Fibrosis and Cardiomyocyte Hypertrophy in Hypertensive Mice Treated With Spironolactone

Background: Nearly 50% of patients with heart failure (HF) have preserved LV ejection fraction, with interstitial fibrosis and cardiomyocyte hypertrophy as early manifestations of pressure overload. However, methods to assess both tissue characteristics dynamically and noninvasively with therapy are lacking. We measured the effects of mineralocorticoid receptor blockade on tissue phenotypes in LV pressure overload using cardiac magnetic resonance (CMR). Methods and Results: Mice were randomized to l‐nitro‐ω‐methyl ester (l‐NAME, 3 mg/mL in water; n=22), or l‐NAME with spironolactone (50 mg/kg/day in subcutaneous pellets; n=21). Myocardial extracellular volume (ECV; marker of diffuse interstitial fibrosis) and the intracellular lifetime of water (τic; marker of cardiomyocyte hypertrophy) were determined by CMR T1 imaging at baseline and after 7 weeks of therapy alongside histological assessments. Administration of l‐NAME induced hypertensive heart disease in mice, with increases in mean arterial pressure, LV mass, ECV, and τic compared with placebo‐treated controls, while LV ejection fraction was preserved (>50%). In comparison, animals receiving both spironolactone and l‐NAME (“l‐NAME+S”) showed less concentric remodeling, and a lower myocardial ECV and τic, indicating decreased interstitial fibrosis and cardiomyocyte hypertrophy (ECV: 0.43±0.09 for l‐NAME versus 0.25±0.03 for l‐NAME+S, P<0.001; τic: 0.42±0.11 for l‐NAME groups versus 0.12±0.05 for l‐NAME+S group). Mice treated with a combination of l‐NAME and spironolactone were similar to placebo‐treated controls at 7 weeks. Conclusions: Spironolactone attenuates interstitial fibrosis and cardiomyocyte hypertrophy in hypertensive heart disease. CMR can phenotype myocardial tissue remodeling in pressure‐overload, furthering our understanding of HF progression

Upfront dexrazoxane for the reduction of anthracycline-induced cardiotoxicity in adults with preexisting cardiomyopathy and cancer: a consecutive case series

Abstract Background Cardiotoxicity associated with anthracycline-based chemotherapies has limited their use in patients with preexisting cardiomyopathy or heart failure. Dexrazoxane protects against the cardiotoxic effects of anthracyclines, but in the USA and some European countries, its use had been restricted to adults with advanced breast cancer receiving a cumulative doxorubicin (an anthracycline) dose > 300 mg/m2. We evaluated the off-label use of dexrazoxane as a cardioprotectant in adult patients with preexisting cardiomyopathy, undergoing anthracycline chemotherapy. Methods Between July 2015 and June 2017, five consecutive patients, with preexisting, asymptomatic, systolic left ventricular (LV) dysfunction who required anthracycline-based chemotherapy, were concomitantly treated with off-label dexrazoxane, administered 30 min before each anthracycline dose, regardless of cancer type or stage. Demographic, cardiovascular, and cancer-related outcomes were compared to those of three consecutive patients with asymptomatic cardiomyopathy treated earlier at the same hospital without dexrazoxane. Results Mean age of the five dexrazoxane-treated patients and three patients treated without dexrazoxane was 70.6 and 72.6 years, respectively. All five dexrazoxane-treated patients successfully completed their planned chemotherapy (doxorubicin, 280 to 300 mg/m2). With dexrazoxane therapy, changes in LV systolic function were minimal with mean left ventricular ejection fraction (LVEF) decreasing from 39% at baseline to 34% after chemotherapy. None of the dexrazoxane-treated patients experienced symptomatic heart failure or elevated biomarkers (cardiac troponin I or brain natriuretic peptide). Of the three patients treated without dexrazoxane, two received doxorubicin (mean dose, 210 mg/m2), and one received daunorubicin (540 mg/m2). Anthracycline therapy resulted in a marked reduction in LVEF from 42.5% at baseline to 18%. All three developed symptomatic heart failure requiring hospitalization and intravenous diuretic therapy. Two of them died from cardiogenic shock and multi-organ failure. Conclusion The concomitant administration of dexrazoxane in patients with preexisting cardiomyopathy permitted successful delivery of anthracycline-based chemotherapy without cardiac decompensation. Larger prospective trials are warranted to examine the use of dexrazoxane as a cardioprotectant in patients with preexisting cardiomyopathy who require anthracyclines.https://deepblue.lib.umich.edu/bitstream/2027.42/147463/1/40959_2019_Article_36.pd

Effect of Sleep Apnea and Continuous Positive Airway Pressure on Cardiac Structure and Recurrence of Atrial Fibrillation

Background: Sleep apnea (SA) is associated with an increased risk of atrial fibrillation (AF). We sought to determine the effect of SA on cardiac structure in patients with AF, whether therapy for SA was associated with beneficial cardiac structural remodelling, and whether beneficial cardiac structural remodelling translated into a reduced risk of recurrence of AF after pulmonary venous isolation (PVI). Methods and Results: A consecutive group of 720 patients underwent a cardiac magnetic resonance study before PVI. Patients with SA (n=142, 20%) were more likely to be male, diabetic, and hypertensive and have an increased pulmonary artery pressure, right ventricular volume, atrial dimensions, and left ventricular mass. Treated SA was defined as duration of continuous positive airway pressure therapy of >4 hours per night. Treated SA patients (n=71, 50%) were more likely to have paroxysmal AF, a lower blood pressure, lower ventricular mass, and smaller left atrium. During a follow‐up of 42 months, AF recurred in 245 patients. The cumulative incidence of AF recurrence was 51% in patients with SA, 30% in patients without SA, 68% in patients with untreated SA, and 35% in patients with treated SA. In a multivariable model, the presence of SA (hazard ratio 2.79, CI 1.97 to 3.94, P<0.0001) and untreated SA (hazard ratio 1.61, CI 1.35 to 1.92, P<0.0001) were highly associated with AF recurrence. Conclusions: Patients with SA have an increased blood pressure, pulmonary artery pressure, right ventricular volume, left atrial size, and left ventricular mass. Therapy with continuous positive airway pressure is associated with lower blood pressure, atrial size, and ventricular mass, and a lower risk of AF recurrence after PVI