89 research outputs found
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The Effect of Salsalate Therapy on Endothelial Function in a Broad Range of Subjects
Background: Inflammation is fundamental to the development of atherosclerosis. We examined the effect of antiâinflammatory doses of salicylate on endotheliumâdependent vasodilation, a biomarker of cardiovascular risk, in a broad range of subjects. Methods and Results: We performed a randomized, doubleâblind, placeboâcontrolled crossover trial evaluating the effects of 4 weeks of highâdose salsalate (disalicylate) therapy on endotheliumâdependent flowâmediated and endotheliumâindependent vasodilation. Fiftyâeight subjects, including 17 with metabolic syndrome, 13 with atherosclerosis, and 28 healthy controls, were studied. Among all subjects, endotheliumâdependent flowâmediated vasodilation decreased after salsalate compared with placebo therapy (P=0.01), whereas nitroglycerinâmediated, endotheliumâindependent vasodilation was unchanged (P=0.97). Endotheliumâdependent flowâmediated vasodilation after salsalate therapy was impaired compared with placebo therapy in subjects with therapeutic salicylate levels (n=31, P0.2). Conclusions: Salsalate therapy, particularly when therapeutic salicylate levels are achieved, impairs endotheliumâdependent vasodilation in a broad range of subjects. These data raise concern about the possible deleterious effects of antiâinflammatory doses of salsalate on cardiovascular risk. Clinical Trial Registration URL: www.clinicaltrials.gov. Unique Identifiers: NCT00760019 and NCT00762827
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Efficacy of Neurohormonal Therapies in Preventing Cardiotoxicity in Patients with Cancer Undergoing Chemotherapy.
BACKGROUND: Various cardioprotective approaches have been evaluated to prevent chemotherapy-related cardiotoxicity; however, their overall utility remains uncertain. OBJECTIVES: To assess the effects of neurohormonal therapies in preventing cardiotoxicity in patients receiving chemotherapy. METHODS: This meta-analysis included randomized clinical trials of adult patients that underwent chemotherapy and neurohormonal therapies (beta-blockers, mineralocorticoid receptor antagonists, or ACE inhibitors/ARBs) vs. placebo with follow-up â„4 weeks. The primary outcome was change in left ventricular ejection fraction (LVEF) from baseline to the end of trial. Other outcomes of interest were measures of LV size, strain, and diastolic function. Pooled estimates for each outcome were reported as standardized mean difference (SMD) and weighted mean difference (WMD) between the neurohormonal therapy and placebo groups using random effects models. RESULTS: We included 17 trials, collectively enrolling 1,984 participants. In pooled analysis, neurohormonal therapy (vs. placebo) was associated with significantly higher LVEF on follow-up [SMD(95% CI): +1.04(0.57 to 1.50)] but with significant heterogeneity in the pooled estimate (I2 = 96%). Compared with placebo-treated patients, those randomized to neurohormonal therapies experienced a 3.96% (95%CI: 2.9% to 5.0%) less decline in LVEF estimated by WMD, but with significant heterogeneity (I2 = 98%). There was a trend towards lower adverse clinical events with neurohormonal therapy (vs. placebo) without statistical significance [risk ratio(95%CI): 0.80(0.53-1.20) I2 = 71%]. CONCLUSIONS: Neurohormonal therapies are associated with higher LVEF in follow-up among cancer patients receiving chemotherapy, although absolute changes in LVEF are small and may be within inter-test variability. Furthermore, significant heterogeneity is observed in the treatment effects across studies highlighting the need for larger trials of cardioprotective strategies
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 >â300âmg/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 30âmin 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 72.6âyears, respectively. All five dexrazoxane-treated patients successfully completed their planned chemotherapy (doxorubicin, 280 to 300âmg/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, 210âmg/m2), and one received daunorubicin (540âmg/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
Myocarditis in Patients Treated With Immune Checkpoint Inhibitors.
BACKGROUND: Myocarditis is an uncommon, but potentially fatal, toxicity of immune checkpoint inhibitors (ICI). Myocarditis after ICI has not been well characterized. OBJECTIVES: The authors sought to understand the presentation and clinical course of ICI-associated myocarditis. METHODS: After observation of sporadic ICI-associated myocarditis cases, the authors created a multicenter registry with 8 sites. From November 2013 to July 2017, there were 35 patients with ICI-associated myocarditis, who were compared to a random sample of 105 ICI-treated patients without myocarditis. Covariates of interest were extracted from medical records including the occurrence of major adverse cardiac events (MACE), defined as the composite of cardiovascular death, cardiogenic shock, cardiac arrest, and hemodynamically significant complete heart block. RESULTS: The prevalence of myocarditis was 1.14% with a median time of onset of 34 days after starting ICI (interquartile range: 21 to 75 days). Cases were 65 ± 13 years of age, 29% were female, and 54% had no other immune-related side effects. Relative to controls, combination ICI (34% vs. 2%; p < 0.001) and diabetes (34% vs. 13%; p = 0.01) were more common in cases. Over 102 days (interquartile range: 62 to 214 days) of median follow-up, 16 (46%) developed MACE; 38% of MACE occurred with normal ejection fraction. There was a 4-fold increased risk of MACE with troponin T of â„1.5 ng/ml (hazard ratio: 4.0; 95% confidence interval: 1.5 to 10.9; p = 0.003). Steroids were administered in 89%, and lower steroids doses were associated with higher residual troponin and higher MACE rates. CONCLUSIONS: Myocarditis after ICI therapy may be more common than appreciated, occurs early after starting treatment, has a malignant course, and responds to higher steroid doses
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MYOCARDIAL T1 AND T2 MAPPING BY CARDIOVASCULAR MAGNETIC RESONANCE IN IMMUNE CHECKPOINT INHIBITOR-ASSOCIATED MYOCARDITIS
Electrocardiographic features of immune checkpoint inhibitor associated myocarditis.
BACKGROUND: Myocarditis is a highly morbid complication of immune checkpoint inhibitor (ICI) use that remains inadequately characterized. The QRS duration and the QTc interval are standardized electrocardiographic measures that are prolonged in other cardiac conditions; however, there are no data on their utility in ICI myocarditis.
METHODS: From an international registry, ECG parameters were compared between 140 myocarditis cases and 179 controls across multiple time points (pre-ICI, on ICI prior to myocarditis, and at the time of myocarditis). The association between ECG values and major adverse cardiac events (MACE) was also tested.
RESULTS: Both the QRS duration and QTc interval were similar between cases and controls prior to myocarditis. When compared with controls on an ICI (93±19 ms) or to baseline prior to myocarditis (97±19 ms), the QRS duration prolonged with myocarditis (110±22 ms, p
CONCLUSIONS: The QRS duration is increased in ICI myocarditis and is associated with increased MACE risk. Use of this widely available ECG parameter may aid in ICI myocarditis diagnosis and risk-stratification
COVID-19 Severity and Cardiovascular Outcomes in SARS-CoV-2-Infected Patients With Cancer and Cardiovascular Disease
BACKGROUND: Data regarding outcomes among patients with cancer and co-morbid cardiovascular disease (CVD)/cardiovascular risk factors (CVRF) after SARS-CoV-2 infection are limited.
OBJECTIVES: To compare Coronavirus disease 2019 (COVID-19) related complications among cancer patients with and without co-morbid CVD/CVRF.
METHODS: Retrospective cohort study of patients with cancer and laboratory-confirmed SARS-CoV-2, reported to the COVID-19 and Cancer Consortium (CCC19) registry from 03/17/2020 to 12/31/2021. CVD/CVRF was defined as established CVD
RESULTS: Among 10,876 SARS-CoV-2 infected patients with cancer (median age 65 [IQR 54-74] years, 53% female, 52% White), 6253 patients (57%) had co-morbid CVD/CVRF. Co-morbid CVD/CVRF was associated with higher COVID-19 severity (adjusted OR: 1.25 [95% CI 1.11-1.40]). Adverse CV events were significantly higher in patients with CVD/CVRF (all
CONCLUSIONS: Co-morbid CVD/CVRF is associated with higher COVID-19 severity among patients with cancer, particularly those not receiving active cancer therapy. While infrequent, COVID-19 related CV complications were higher in patients with comorbid CVD/CVRF. (COVID-19 and Cancer Consortium Registry [CCC19]; NCT04354701)
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