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

Focused cardiopulmonary ultrasound for assessment of dyspnea in a resource-limited setting

Abstract Background The diagnosis and management of acutely dyspneic patients in resource-limited developing world settings poses a particular challenge. Focused cardiopulmonary ultrasound (CPUS) may assist in the emergency diagnosis and management of patients with acute dyspnea by identifying left ventricular systolic dysfunction, pericardial effusion, interstitial pulmonary edema, and pleural effusion. We sought to assess the accuracy of emergency providers performing CPUS after a training intervention in a limited-resource setting; a secondary objective was to assess the ability of CPUS to affect change of clinician diagnostic assessment and acute management in patients presenting with undifferentiated dyspnea. Methods and results After a training intervention for Haitian emergency providers, patients with dyspnea presenting urgently to a regional referral center in Haiti underwent a rapid CPUS examination by the treating physician. One hundred seventeen patients (median age of 36 years, 56 % female) were prospectively evaluated with a standardized CPUS exam. Blinded expert review of ultrasound images was performed by two board certified cardiologists and one ultrasound fellowship trained emergency physician. Inter-observer agreement was determined using an agreement coefficient (kappa). Sensitivity and Specificity with confidence intervals were calculated. Pre-test and post-test clinician impressions and management plans were compared to assess for a change. We enrolled 117 patients with undifferentiated dyspnea. Upon expert image review, prevalence of left ventricular systolic dysfunction was 40.2 %, and in those with systolic dysfunction, the average EF was 14 % (±9 %). The parasternal long axis (PLAX) single view was predictive of an overall abnormal echo with PPV of abnormal PLAX 95 % and NPV 93 % of normal PLAX. Weighted kappa for pericardial effusion between the Haitian physicians and two cardiology reviewers was 0.81 (95 % CI 0.75–0.87, p value <0.001) and for ejection fraction was 0.98 (95 % CI 0.98–0.99, p value <0.001). For lung ultrasound, a kappa statistic assessing agreement between the Haitian physician and the EP for pleural effusion was 0.73, and for interstitial syndrome was 0.49. Detailed test characteristics are detailed in Table 3. Overall, there was a change in treating clinician impression in 15.4 % (95 % CI 9–22 %) and change in management in 19.6 % (95 % CI 12–27 %) of patients following CPUS. A significant structural heart disease was common: 48 % of patients were noted to have abnormal right ventricular systolic function, 36 % had at least moderate mitral regurgitation, and 7.7 % had a moderate to large pericardial effusion. Conclusions A focused training intervention in CPUS was sufficient for providers in a limited-resource setting to accurately identify left ventricular systolic dysfunction, pericardial effusion, evidence of interstitial syndrome, and pleural effusions in dyspneic patients. Clinicians were able to integrate CPUS into their clinical impressions and management plans and reported a high level of confidence in their ultrasound findings