The field of cardio-oncology was born from the necessity for recognition and management of cardiovascular diseases among patients with cancer. This need for this specialty continues to grow as patients with cancer live longer as a result of lifesaving targeted and immunologic cancer therapies beyond the usual chemotherapy and/or radiation therapy. Often, potentially cardiotoxic anticancer treatment is necessary in patients with baseline cardiovascular disease. Moreover, patients may need to continue therapy in the setting of incident cancer therapy–associated cardiotoxicity. Herein, we present and discuss the concept of permissive cardiotoxicity as a novel term that represents an essential concept in the field of cardio-oncology and among practicing cardio-oncology specialists. It emphasizes a proactive rather than reactive approach to continuation of lifesaving cancer therapies in order to achieve the best oncologic outcome while mitigating associated and potentially off-target cardiotoxicities.

Hematopoietic stem cell transplantation (HSCT) is associated with various cardiovascular (CV) complications. We sought to characterize the incidence and risk factors for short-term and long-term CV events in a contemporary cohort of adult HSCT recipients. We conducted a multicenter observational study of adult patients who underwent autologous or allogeneic HSCT between 2008 and 2019. Data on demographics, clinical characteristics, conditioning regimen, and CV outcomes were collected through chart review. CV outcomes were a composite of CV death, myocardial infarction, heart failure, atrial fibrillation/flutter, stroke, and sustained ventricular tachycardia and were classified as short-term (≤100 days post-HSCT) or long-term (>100 days post-HSCT). In 3,354 patients (mean age 55 years; 40.9% female; 30.1% Black) followed for a median time of 2.3 years (Q1-Q3: 1.0-5.4 years), the 100-day and 5-year cumulative incidences of CV events were 4.1% and 13.9%, respectively. Atrial fibrillation/flutter was the most common short- and long-term CV event, with a 100-day incidence of 2.6% and a 5-year incidence of 6.8% followed by heart failure (1.1% at 100 days and 5.4% at 5 years). Allogeneic recipients had a higher incidence of long-term CV events compared to autologous recipients (5-year incidence 16.4% vs 12.1%; P = 0.002). Baseline CV comorbidities were associated with a higher risk of long-term CV events. The incidence of short-term CV events in HSCT recipients is relatively low. Long-term events were more common among allogeneic recipients and those with pre-existing CV comorbidities.

Background: Immune checkpoint inhibitors (ICIs) have uncommon associations with cardiotoxicity, yet these cardiotoxic effects are associated with high mortality. An accurate assessment of risk for cardiotoxicity is essential for clinical decision‐making, but data from randomized controlled trials often differ from real‐world observational studies. Methods and Results: A systematic search of PubMed, Embase, Cochrane Library, and Scopus was performed, including phase II and III randomized controlled trials (RCTs) and observational studies (OSs) reporting myocarditis or pericardial disease, myocardial infarction, or stroke with an immunotherapy. Odds ratios (ORs) were used to pool results between ICIs and other cancer therapy in RCTs and OSs. The Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guideline was followed. In total, 54 RCTs (N=38 264) and 24 OSs (N=12 561 455) were included. In RCTs, ICI use resulted in higher risk of myocarditis (OR, 3.55 [95% CI, 2.10–5.98]), pericardial disease (OR, 2.73 [95% CI, 1.57–4.77]), and myocardial infarction (OR, 1.83 [95% CI, 1.03–3.25]), compared with non‐ICI (placebo or chemotherapy). In OSs, ICI use was not associated with myocarditis, pericardial disease, or myocardial infarction compared with controls; however, combination ICIs demonstrated higher risk of myocarditis compared with single ICI use (OR, 3.07 [95% CI, 1.28–7.39]). Stroke risk was not increased with use of ICIs in RCTs. Conclusions: We demonstrated increased risk of ICI myocarditis, pericardial disease, and myocardial infarction in RCTs but not OSs. Results of this study suggest there are differences between ICI cardiotoxicity risk, possibly suggesting differences in diagnoses and management, in clinical trials versus the OSs.