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A 76-year-old man was admitted to the hospital with acute onset of involuntary movements of the left side of his body. His neurological examination revealed he was oriented only to himself, and aforementioned movements of his left arm and leg. CT head demonstrated old infarcts in his right aspect of his pons and basal ganglia. Cerebrospinal fluid analysis was unremarkable. He initially had a normal blood glucose with an elevated anion gap and elevated creatine kinase. Brain MRI showed a small lacunar-type ischaemic infarct within the anteromedial aspect of the right cerebral peduncle, which localised to his haemiballism. To prevent worsening rhabdomyolysis associated with his haemiballism, the primary team initiated both tetrabenazine and diazepam. His movements improved after 1 week of medication therapy. This report discusses a thorough workup for this movement disorder and when to intervene for this distressing condition.

Impaired MFR in the absence of flow-limiting CAD is associated with adverse events. Cardiovascular disease is an important cause of morbidity and mortality in patients with breast cancer. We sought to test the utility of MFR to predict outcomes in a cohort of patients with breast cancer. We retrospectively studied consecutive patients with breast cancer or breast cancer survivors who underwent cardiac stress PET imaging from 2006 to 2017 at Brigham and Women’s Hospital. Patients with a history of clinically overt CAD, LVEF < 45%, or abnormal myocardial perfusion were excluded. Subjects were followed from time of PET to the occurrence of a first major adverse cardiovascular event (MACE) and all-cause death. The final cohort included 87 patients (median age 69.0 years, 98.9% female, mean MFR 2.05). Over a median follow-up of 7.6 years after PET, the lowest MFR tertile was associated with higher cumulative incidence of MACE (adjusted subdistribution hazard ratio 4.91; 95% CI 1.68-14.38; p = 0.004) when compared with the highest MFR tertile. In patients with breast cancer, coronary vasomotor dysfunction was associated with incident cardiovascular events. MFR may have potential as a risk stratification biomarker among patients with/survivors of breast cancer.

Patients with locally advanced non-small cell lung cancer (LA-NSCLC) have a high prevalence of pre-existing coronary heart disease and face excess cardiac risk after thoracic radiation therapy. We sought to assess whether statin therapy is a predictor of overall survival (OS) after thoracic radiation therapy.We performed a retrospective analysis of 748 patients with LA-NSCLC treated with thoracic radiation therapy, using Kaplan-Meier OS estimates and Cox regression.Statin use among high cardiac risk patients (Framingham risk ≥20% or pre-existing coronary heart disease; n = 496) was 51.2%. After adjustment for baseline cardiac risk and other prognostic factors, statin therapy was associated with a significantly increased risk of all-cause mortality (adjusted hazard ratio, 1.39; 95% confidence interval [CI], 1.00-1.91; P = .048) but not major adverse cardiac events (adjusted hazard ratio, 1.18; 95% CI, 0.52-2.68; P = .69). Among statin-naïve patients, mean heart dose ≥10 Gy versus10 Gy was associated with a significantly increased risk of all-cause mortality (hazard ratio, 1.32; 95% CI, 1.04-1.68; P = .022), with 2-year OS estimates of 46.9% versus 60.0%, respectively. However, OS did not differ by heart dose among patients on statin therapy (hazard ratio, 1.00; 95% CI, 0.76-1.32; P = 1.00; P-interaction = .031), with 2-year OS estimates of 46.9% versus 50.3%, respectively.Among patients with LA-NSCLC, only half of statin-eligible high cardiac risk patients were on statin therapy, reflecting the highest cardiac risk level of our cohort. Statin use was an independent predictor of all-cause mortality but not major adverse cardiac events. Elevated mean heart dose (≥10 Gy) was associated with increased risk of all-cause mortality in statin-naïve patients but not among those on statin therapy, identifying a group of patients in which early intervention with statins may mitigate the deleterious effects of high heart radiation therapy dose. This warrants evaluation in prospective trials.

Mean heart dose (MHD) over 10 Gy and left anterior descending (LAD) coronary artery volume (V) receiving 15 Gy (V15Gy) greater than 10% can significantly increase the risk of major adverse cardiac events (MACE) in patients with non-small cell lung cancer (NSCLC). We sought to characterize the discordance between MHD and LAD dose and the association of this classification on the risk of MACE after radiation therapy.The coefficient of determination for MHD and LAD V15Gy was calculated in this retrospective analysis of 701 patients with locally advanced NSCLC treated with radiation therapy. Four groups were defined on the basis of high or low MHD (≥10 Gy vs10 Gy) and LAD V15Gy (≥10% vs10%). MACE (unstable angina, heart failure, myocardial infarction, coronary revascularization, and cardiac death) cumulative incidence was estimated, and Fine and Gray regressions were performed.The proportion of variance in LAD V15Gy predictable from MHD was only 54.5% (RMHD is insufficient to predict LAD V15Gy with confidence. When MHD and LAD V15Gy dose exposure is discordant, isolated low LAD V15Gy significantly reduces the risk of MACE in patients with locally advanced NSCLC after radiation therapy, suggesting that the validity of whole heart metrics for optimally predicting cardiac events should be reassessed.

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Background For men with radiation-managed prostate cancer, there is conflicting evidence regarding the association between androgen deprivation therapy (ADT) and cardiovascular mortality (CVM), particularly among those who have with preexisting comorbidities. The objective of this study was to analyze the association between ADT and CVM across patient comorbidity status using prospectively collected data from a large clinical trial. Methods In total, 1463 men were identified who were diagnosed with clinically localized, intermediate-risk/high-risk prostate cancer (T2b-T4, Gleason 7-10, or prostate-specific antigen >10 ng/mL) from 1993 to 2001 and managed with either radiation therapy (RT) alone or RT plus ADT during the randomized Prostate, Lung, Colon, and Ovarian (PLCO) Cancer Screening Trial. Adjusted hazard ratios (aHRs) for cause-specific mortality (prostate cancer-specific mortality vs other-cause mortality-including the primary end point of CVM [death from ischemic heart disease, cerebrovascular accident, or other circulatory disease]) were determined using Fine and Gray competing-risk regression analysis and stratified by comorbidity history. Results There was no difference in the risk of 5-year CVM between ADT plus RT and RT alone (2.3% vs 3.3%, respectively; aHR, 0.69; 95% CI, 0.38-1.24; P = .21) overall or on subgroup analysis among men with a history of ≥1 preexisting comorbidities (3.2% vs 5.3%, respectively; aHR, 0.83; 95% CI, 0.43-1.60; P = .58), ≥2 preexisting comorbidities (6.9% vs 8.3%, respectively; aHR, 0.95; 95% CI, 0.40-2.25; P = .90), or cardiovascular disease/risk factors (3.6% vs 4.3%, respectively; aHR, 0.85; 95% CI, 0.44-1.65; P = .63). These results were all similar when each component of CVM was analyzed separately-either cardiac, stroke, or other vascular mortality (P > .05). Conclusions This study provides prospectively collected evidence that the use of ADT plus RT, compared with RT alone, is not associated with an increased risk of CVM, even among subgroups of men who have preexisting comorbidities and cardiovascular disease.

Giant cell myocarditis is a rare, often rapidly progressive and potentially fatal, disease due to T-cell lymphocyte-mediated inflammation of the myocardium that typically affects young and middle-aged adults. Frequently, the disease course is marked by acute heart failure, cardiogenic shock, intractable ventricular arrhythmias, and/or heart block. Diagnosis is often difficult due to its varied clinical presentation and overlap with other cardiovascular conditions. Although cardiac biomarkers and multimodality imaging are often used as initial diagnostic tests, endomyocardial biopsy is required for definitive diagnosis. Combination immunosuppressive therapy, along with guideline-directed medical therapy, has led to a paradigm shift in the management of giant cell myocarditis resulting in an improvement in overall and transplant-free survival. Early diagnosis and prompt management can decrease the risk of transplantation or death, which remain common in patients who present with cardiogenic shock.

Background: Cancer and cardiovascular disease (CVD) are independently associated with adverse outcomes in patients with COVID-19. However, outcomes in patients with COVID-19 with both cancer and comorbid CVD are unknown. Methods: This retrospective study included 2,476 patients who tested positive for SARS-CoV-2 at 4 Massachusetts hospitals between March 11 and May 21, 2020. Patients were stratified by a history of either cancer (n=195) or CVD (n=414) and subsequently by the presence of both cancer and CVD (n=82). We compared outcomes between patients with and without cancer and patients with both cancer and CVD compared with patients with either condition alone. The primary endpoint was COVID-19–associated severe disease, defined as a composite of the need for mechanical ventilation, shock, or death. Secondary endpoints included death, shock, need for mechanical ventilation, need for supplemental oxygen, arrhythmia, venous thromboembolism, encephalopathy, abnormal troponin level, and length of stay. Results: Multivariable analysis identified cancer as an independent predictor of COVID-19–associated severe disease among all infected patients. Patients with cancer were more likely to develop COVID-19–associated severe disease than were those without cancer (hazard ratio [HR], 2.02; 95% CI, 1.53–2.68; PP=.02) or CVD (HR, 1.79; 95% CI, 1.21–2.66; P=.004) alone. Patients died more frequently if they had both cancer and CVD compared with either cancer (35% vs 17%; P=.004) or CVD (35% vs 21%; P=.009) alone. Arrhythmias and encephalopathy were also more frequent in patients with both cancer and CVD compared with those with cancer alone. Conclusions: Patients with a history of both cancer and CVD are at significantly higher risk of experiencing COVID-19–associated adverse outcomes. Aggressive public health measures are needed to mitigate the risks of COVID-19 infection in this vulnerable patient population.

Background and aim Low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) diet improves irritable bowel syndrome (IBS) symptoms. Data on long-term "modified" FODMAP diet are emerging. We aimed to assess efficacy and acceptability of short-term "strict" low FODMAP diet (LFD) and long-term "modified" FODMAP diet in patients with diarrhea-predominant IBS (IBS-D). Methods This prospective randomized trial included patients with IBS-D (Rome IV) and IBS severity scoring system (IBS-SSS) ≥ 175. In phase I (4 weeks), patients were randomized to strict LFD and traditional dietary advice (TDA) groups. From 4 to 16 weeks, LFD group was advised systematic reintroduction of FODMAPs ("modified" FODMAP diet). Response was defined as > 50-point reduction in IBS-SSS. Results Of the total 166 patients with IBS-D screened, 101 (mean age 41.9 ± 17.1 years, 58% male) were randomized to LFD (n = 52) and TDA (n = 49) groups. Both at 4 and 16 weeks, total IBS-SSS and IBS quality of life score reduced significantly in both groups, but there was significantly greater reduction in LFD group. By intention-to-treat analysis, responders in LFD group were significantly higher than TDA group (4 weeks-62.7% [32/51] vs 40.8% [20/49], respectively, P = 0.0448; 16 weeks-52.9% [27/51] vs 30.6% [15/49], respectively; P = 0.0274). Compliance to LFD was 93% at 4 weeks and 64% at 16 weeks. Energy, carbohydrate, fat, and fiber intake showed reduction in LFD group at 4 weeks, which improved till 16 weeks. Conclusions Strict LFD for short-term and "modified" LFD for long term in IBS-D patients is acceptable and leads to significant improvement in symptoms and quality of life.

Whether to repair nonsevere tricuspid regurgitation (TR) during surgery for ischemic mitral valve regurgitation (IMR) remains uncertain.The goal of this study was to investigate the incidence, predictors, and clinical significance of TR progression and presence of ≥moderate TR after IMR surgery.Patients (n = 492) with untreated nonsevere TR within 2 prospectively randomized IMR trials were included. Key outcomes were TR progression (either progression by ≥2 grades, surgery for TR, or severe TR at 2 years) and presence of ≥moderate TR at 2 years.Patients' mean age was 66 ± 10 years (67% male), and TR distribution was 60% ≤trace, 31% mild, and 9% moderate. Among 2-year survivors, TR progression occurred in 20 (6%) of 325 patients. Baseline tricuspid annular diameter (TAD) was not predictive of TR progression. At 2 years, 37 (11%) of 323 patients had ≥moderate TR. Baseline TR grade, indexed TAD, and surgical ablation for atrial fibrillation were independent predictors of ≥moderate TR. However, TAD alone had poor discrimination (area under the curve, ≤0.65). Presence of ≥moderate TR at 2 years was higher in patients with MR recurrence (20% vs. 9%; p = 0.02) and a permanent pacemaker/defibrillator (19% vs. 9%; p = 0.01). Clinical event rates (composite of ≥1 New York Heart Association functional class increase, heart failure hospitalization, mitral valve surgery, and stroke) were higher in patients with TR progression (55% vs. 23%; p = 0.003) and ≥moderate TR at 2 years (38% vs. 22%; p = 0.04).After IMR surgery, progression of unrepaired nonsevere TR is uncommon. Baseline TAD is not predictive of TR progression and is poorly discriminative of ≥moderate TR at 2 years. TR progression and presence of ≥moderate TR are associated with clinical events. (Comparing the Effectiveness of a Mitral Valve Repair Procedure in Combination With Coronary Artery Bypass Grafting [CABG] Versus CABG Alone in People With Moderate Ischemic Mitral Regurgitation, NCT00806988; Comparing the Effectiveness of Repairing Versus Replacing the Heart's Mitral Valve in People With Severe Chronic Ischemic Mitral Regurgitation, NCT00807040).

PURPOSE Survivors of childhood cancer treated with anthracyclines and/or chest-directed radiation are at increased risk for heart failure (HF). The International Late Effects of Childhood Cancer Guideline Harmonization Group (IGHG) recommends risk-based screening echocardiograms, but evidence supporting its frequency and cost-effectiveness is limited. PATIENTS AND METHODS Using the Childhood Cancer Survivor Study and St Jude Lifetime Cohort, we developed a microsimulation model of the clinical course of HF. We estimated long-term health outcomes and economic impact of screening according to IGHG-defined risk groups (low [doxorubicin-equivalent anthracycline dose of 1-99 mg/m2 and/or radiotherapy < 15 Gy], moderate [100 to < 250 mg/m2 or 15 to < 35 Gy], or high [≥ 250 mg/m2 or ≥ 35 Gy or both ≥ 100 mg/m2 and ≥ 15 Gy]). We compared 1-, 2-, 5-, and 10-year interval-based screening with no screening. Screening performance and treatment effectiveness were estimated based on published studies. Costs and quality-of-life weights were based on national averages and published reports. Outcomes included lifetime HF risk, quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (ICERs). Strategies with ICERs < $100,000 per QALY gained were considered cost-effective. RESULTS Among the IGHG risk groups, cumulative lifetime risks of HF without screening were 36.7% (high risk), 24.7% (moderate risk), and 16.9% (low risk). Routine screening reduced this risk by 4% to 11%, depending on frequency. Screening every 2, 5, and 10 years was cost-effective for high-risk survivors, and every 5 and 10 years for moderate-risk survivors. In contrast, ICERs were > $175,000 per QALY gained for all strategies for low-risk survivors, representing approximately 40% of those for whom screening is currently recommended. CONCLUSION Our findings suggest that refinement of recommended screening strategies for IGHG high- and low-risk survivors is needed, including careful reconsideration of discontinuing asymptomatic left ventricular dysfunction and HF screening in low-risk survivors.

Background Heart failure (HF) and breast cancer are 2 of the leading causes of death in postmenopausal women. The temporal association between HF and breast cancer in postmenopausal women has not been described. Objectives This study sought to examine the temporal association between HF and breast cancer. Methods Postmenopausal women within the WHI (Women’s Health Initiative) cohort were studied. All prevalent HF and prevalent breast cancer at enrollment were self-reported. Incident hospitalized HF and breast cancer diagnoses were adjudicated through 2017. Results Among a cohort of 44,174 women (mean age 63 ± 7 years), 2,188 developed incident invasive breast cancer and 2,416 developed incident hospitalized HF over a median follow-up of 14 and 15 years, respectively. When compared with a breast cancer- and HF-free cohort, there was no association between prevalent HF and incident invasive breast cancer and similarly, there was no association between prevalent breast cancer and incident hospitalized HF. Across the entire cohort, the median survival after incident hospitalized HF was worse compared with an incident invasive breast cancer diagnosis (5 and 19 years, respectively). In women with incident invasive breast cancer, prevalent HF was associated with an increased risk of mortality (hazard ratio: 2.28; 95% confidence interval: 1.31 to 3.95). In women with incident hospitalized HF, prevalent breast cancer was associated with an increased risk of mortality (hazard ratio: 1.66; 95% confidence interval: 1.03 to 2.68). Cause of death after incident HF was different only in women with prevalent and interim breast cancer compared with those without prevalent and interim breast cancer. Conclusions In postmenopausal women, prevalent HF was not associated with a higher incidence of breast cancer and vice versa. However, the presence of incident invasive breast cancer or incident HF in those with prevalent HF or prevalent breast cancer, respectively, was associated with increased mortality., Central Illustration

Patients with pre-existing cardiovascular disease and risk factors are more likely to experience adverse outcomes associated with the novel coronavirus disease-2019 (COVID-19). Additionally, consistent reports of cardiac injury and de novo cardiac complications, including possible myocarditis, arrhythmia, and heart failure in patients without prior cardiovascular disease or significant risk factors, are emerging, possibly due to an accentuated host immune response and cytokine release syndrome. As the spread of the virus increases exponentially, many patients will require medical care either for COVID-19 related or traditional cardiovascular issues. While the COVID-19 pandemic is dominating the attention of the healthcare system, there is an unmet need for a standardized approach to deal with COVID-19 associated and other traditional cardiovascular issues during this period. We provide consensus guidance for the management of various cardiovascular conditions during the ongoing COVID-19 pandemic with the goal of providing the best care to all patients and minimizing the risk of exposure to frontline healthcare workers.

As the novel coronavirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to spread across the globe, millions of people may be affected ([1][1],[2][2]). Although knowledge regarding the complications and fatality rate associated with SARS-CoV-2 (COVID-19) infection is evolving

Cancer patients are increasingly referred for cardiology evaluations. These patients differ from those routinely seen in cardiology clinics because of their psychological burden and because the therapies and cancer itself can cause cardiac symptoms. A humane approach is critical to managing these patients. Cardiologists may see patients who are newly diagnosed with cancer or are in various phases of treatment; these patients may or may not have preexisting cardiac disease, and may develop cardiotoxicity from chemoimmunotherapy or radiotherapy. Each of these situations presents unique communication challenges for cardiologists. Although some oncology centers provide training in communication skills for their personnel, including cardiologists, this training is not widely available to physicians in general hospitals or private practice. This article examines the psychological aspects of cardio-oncology. It offers practical suggestions on how to best communicate with cancer patients in different phases of oncology care, and discusses when professional psychological help is needed.

Aims The prognostic importance of post-diagnosis assessment of cardiorespiratory fitness (CRF) in cancer patients is not well established. We sought to examine the association between CRF and mortality in cancer patients. Methods and results This was a single-centre cohort analysis of 1632 patients (58% male; 64 ± 12 years) with adult-onset cancer who were clinically referred for exercise treadmill testing a median of 7 [interquartile range (IQR): 3–12] years after primary diagnosis. Cardiorespiratory fitness was defined as peak metabolic equivalents (METs) achieved during standard Bruce protocol and categorized by tertiles. The association between CRF and all-cause and cause-specific mortality was assessed using multivariable Cox proportional hazard models adjusting for important covariates. Median follow-up was 4.6 (IQR: 2.6–7.0) years; a total of 411 deaths (229, 50, and 132 all-cause, cardiovascular (CV), and cancer related, respectively) occurred during this period. Compared with low CRF (range: 1.9–7.6 METs), the adjusted hazard ratio (HR) for all-cause mortality was 0.38 [95% confidence interval (CI): 0.28–0.52] for intermediate CRF (range: 7.7–10.6 METs) and 0.17 (95% CI: 0.11–0.27) for high CRF (range: 10.7–22.0 METs). The corresponding HRs were 0.40 (95% CI: 0.19–0.86) and 0.41 (95% CI: 0.16–1.05) for CV mortality and 0.40 (95% CI: 0.26–0.60) and 0.16 (95% CI: 0.09–0.28) for cancer mortality, respectively. The adjusted risk of all-cause, CV, and cancer mortality decreased by 26%, 14%, and 25%, respectively with each one MET increment in CRF. Conclusion Cardiorespiratory fitness is a strong, independent predictor of all-cause, CV, and cancer mortality, even after adjustment for important clinical covariates in patients with certain cancers.

Background: Due to advances in treatment and early detection, nearly 90% of women with breast cancer are living at least 5 years following their diagnosis. Yet, there is a risk for cardiotoxicity as a result of cancer treatments such as anthracyclines and/or trastuzumab. Recent evidence has demonstrated the potential for statins to mitigate the risk of cardiotoxicity. This systematic review and meta-analysis was aimed to address the research question of: Does statin use lower the risk of cardiotoxicity among breast cancer patients who receive treatment with anthracyclines and/or trastuzumab? Methods: A systematic review of the literature was conducted using the databases PubMed, Embase, Web of Science, ClinicalTrials.gov, and Cochrane Central. Two reviewers independently performed study selection and data extraction. Five studies were identified, of which only one was a prospective randomized controlled trial; all examined statin use among breast cancer patients treated with anthracyclines and/or trastuzumab; four studies examined the primary outcome of cardiotoxicity defined as 1) incidence of heart failure or 2) having a reduction in left ventricular ejection fraction of >10% from baseline to an absolute value of Citation Format: Jacqueline B Vo, Arielle Abovich, Mary Obasi, Yawen Gao, Anju Nohria, Aarti Asnani, Ann H Partridge. Statins to mitigate cardiotoxicity in breast cancer patients treated with anthracyclines and/or trastuzumab: A systematic review and meta-analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-14-06.

BackgroundMyocarditis 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.MethodsFrom 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.ResultsBoth 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, pConclusionsThe 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.

Background Immune checkpoint inhibitor (ICI)-associated myocarditis is associated with a markedly increased risk of morbidity and mortality. The occurrence of ventricular arrhythmias (VA) in patients with ICI-associated myocarditis has not been well characterized. Purpose The aim of this study was to determine the characteristics and risk factors for severe VA in patients with ICI myocarditis. Methods The cohort consisted of 202 patients with ICI myocarditis. Ventricular arrhythmias were defined as a composite of sustained ventricular tachycardia and ventricular fibrillation. We used a multivariable logistic regression model to test the association between clinical variables and the development of VA. Results From a cohort of 202 patients with ICI myocarditis (67±13 years, 35% female, 60% hypertension, 23% diabetes mellitus), 41 (20.3%) developed VA, of which, 33 had VT and 8 had VF. The median time from admission to VF was 144 hours and to VT was 72 hours. A VA occurred in 17.5% of patients with a normal LVEF, and 25% of patients with reduced LVEF. On univariate analysis, a QRS duration >110ms (OR 2.88, 95% CI 1.40 to 6.16, P=0.005) and a QTc duration >470ms were associated with an increased probability of VA (OR 2.58, 95% CI 1.23, 5.41, P=0.012). The association remained significant after adjustment for age and gender. Additionally, a longer time from admission to initiation of corticosteroids was associated with a higher probability of VA (OR 1.06, 95% CI 1.01 to 1.13, P=0.027). The association between the time from admission to administration of corticosteroids and probability of VA remained significant after adjustment for age, gender, and LVEF on admission (OR, 1.06, 95% CI 1.00, 1.13, P=0.037) where each 6-hour delay in the initiation of corticosteroids was associated with a 4% increase in the risk for VA. Conclusions Ventricular arrhythmias are common in the setting of ICI myocarditis and are observed in patients presenting with both a preserved and a reduced LVEF. Wider QRS and longer QT at presentation and longer time from admission to initiation of corticosteroids were associated with an increased risk of VA. Funding Acknowledgement Type of funding sources: None.

Background There are limited data on the occurrence, associations and outcomes of pericardial effusions and pericarditis after treatment with immune checkpoint inhibitors (ICIs). Purpose To evaluate incidence of pericardial disease in patients treated with an ICI. Methods This was a retrospective study at a single academic center that compared 2842 consecutive patients who received ICIs with 2699 age- and cancer-type matched patients with metastatic disease who did not receive ICI (design 1). A pericardial event was defined as a composite outcome of pericarditis and new or worsening moderate or large pericardial effusion. The endpoints were obtained through chart review and were blindly adjudicated. To identify risk factors associated with a pericardial event, in a second analysis, we also compared patients who developed an event on an ICI to patients treated with an ICI who did not develop a pericardial event (design 2). Cox proportional hazard model and logistical regression analysis were performed to study the association between ICI use and pericardial disease as well as pericardial disease and mortality. An additional 6-week landmark analysis was performed to account for lead-time bias. Results There were 42 pericardial events in the patients treated with ICI (n=2842) over 193 days (interquartile range 64 to 411) with an incidence rate of 1.57 events per 100 person-years. There was a 4-fold increase in the risk for pericarditis or a pericardial effusion among patients on an ICI compared to controls not treated with ICI after adjusting for potential confounders (hazard ratio [HR] 4.37, 95% confidence interval [CI] 2.09–9.14, p0.7 mg/kg prednisone) was associated with increased risk of pericardial disease (HR 2.56, 95% CI 1.00–6.57, p=0.049). Conclusions ICI use was associated with an increased risk for development of pericardial disease among cancer patients and a pericardial event on an ICI was associated with a trend towards increased mortality. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): National Institutes of Health/National Heart, Lung, and Blood Institute; a gift from A. Curt Greer and Pamela Kohlberg

Corresponding Author

Introduction: myocarditis is a potentially fatal complication of immune checkpoint inhibitors (ICI). While corticosteroids are the cornerstones of the treatment, there are no data to guide the dose and timing. Methods: from an international registry of patients with ICI myocarditis diagnosed between 2013 and 2019, data on the type, dose (in methylprednisolone equivalent dose) and timing of steroids were extracted. Major cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and hemodynamically-significant complete heart block. Results: in total, 143 ICI myocarditis patients (67±13 years old, 29% women) were included. Among them, 125 received corticosteroids (87%), with the initial agent being either methylprednisolone (95, 76%), prednisone (25, 20%), hydrocortisone (2, 1.6%) or dexamethasone (3, 2.4%). The rates of overall MACE (by admission time tertile 1: 45.8%, tertile 2: 43.8%, tertile 3: 38.3%, P=0.746) and individual elements of MACE were unchanged from 2013 to 2019. The initial corticosteroid dose was categorized as low (500mg). There was an inverse relationship between the occurrence of MACE and initial dose of corticosteroid, where MACE declined with increasing doses (low 61.9%, intermediate 54.6%, high 20.4%, P72 hours (85.7%, P

Author(s): Zhang, Lili; Awadalla, Magid; Mahmood, Syed S; Nohria, Anju; Hassan, Malek Z O; Thuny, Franck; Zlotoff, Daniel A; Murphy, Sean P; Stone, James R; Golden, Doll Lauren Alexandra; Alvi, Raza M; Rokicki, Adam; Jones-O'Connor, Maeve; Cohen, Justine V; Heinzerling, Lucie M; Mulligan, Connor; Armanious, Merna; Barac, Ana; Forrestal, Brian J; Sullivan, Ryan J; Kwong, Raymond Y; Yang, Eric H; Damrongwatanasuk, Rongras; Chen, Carol L; Gupta, Dipti; Kirchberger, Michael C; Moslehi, Javid J; Coelho-Filho, Otavio R; Ganatra, Sarju; Rizvi, Muhammad A; Sahni, Gagan; Tocchetti, Carlo G; Mercurio, Valentina; Mahmoudi, Michael; Lawrence, Donald P; Reynolds, Kerry L; Weinsaft, Jonathan W; Baksi, A John; Ederhy, Stephane; Groarke, John D; Lyon, Alexander R; Fradley, Michael G; Thavendiranathan, Paaladinesh; Neilan, Tomas G | Abstract: Myocarditis is a potentially fatal complication of immune checkpoint inhibitors (ICI). Sparse data exist on the use of cardiovascular magnetic resonance (CMR) in ICI-associated myocarditis. In this study, the CMR characteristics and the association between CMR features and cardiovascular events among patients with ICI-associated myocarditis are presented.From an international registry of patients with ICI-associated myocarditis, clinical, CMR, and histopathological findings were collected. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block. In 103 patients diagnosed with ICI-associated myocarditis who had a CMR, the mean left ventricular ejection fraction (LVEF) was 50%, and 61% of patients had an LVEF ≥50%. Late gadolinium enhancement (LGE) was present in 48% overall, 55% of the reduced EF, and 43% of the preserved EF cohort. Elevated T2-weighted short tau inversion recovery (STIR) was present in 28% overall, 30% of the reduced EF, and 26% of the preserved EF cohort. The presence of LGE increased from 21.6%, when CMR was performed within 4 days of admission to 72.0% when CMR was performed on Day 4 of admission or later. Fifty-six patients had cardiac pathology. Late gadolinium enhancement was present in 35% of patients with pathological fibrosis and elevated T2-weighted STIR signal was present in 26% with a lymphocytic infiltration. Forty-one patients (40%) had MACE over a follow-up time of 5 months. The presence of LGE, LGE pattern, or elevated T2-weighted STIR were not associated with MACE.These data suggest caution in reliance on LGE or a qualitative T2-STIR-only approach for the exclusion of ICI-associated myocarditis.

With the advent of novel cancer therapeutics and improved screening, more patients are surviving a cancer diagnosis or living longer with advanced disease. Many of these treatments have associated cardiovascular toxicities that can manifest in both an acute and a delayed fashion. Arrhythmias are an increasingly identified complication with unique management challenges in the cancer population. The purpose of this scientific statement is to summarize the current state of knowledge regarding arrhythmia identification and treatment in patients with cancer. Atrial tachyarrhythmias, particularly atrial fibrillation, are most common, but ventricular arrhythmias, including those related to treatment-induced QT prolongation, and bradyarrhythmias can also occur. Despite increased recognition, dedicated prospective studies evaluating true incidence are lacking. Moreover, few studies have addressed appropriate prevention and treatment strategies. As such, this scientific statement serves to mobilize the cardio-oncology, electrophysiology, and oncology communities to develop clinical and scientific collaborations that will improve the care of patients with cancer who have arrhythmias.

BackgroundThere are limited data on the occurrence, associations and outcomes of pericardial effusions and pericarditis on or after treatment with immune checkpoint inhibitors (ICIs).MethodsThis was a retrospective study at a single academic center that compared 2842 consecutive patients who received ICIs with 2699 age- and cancer-type matched patients with metastatic disease who did not receive ICI. A pericardial event was defined as a composite outcome of pericarditis and new or worsening moderate or large pericardial effusion. The endpoints were obtained through chart review and were blindly adjudicated. To identify risk factors associated with a pericardial event, we compared patients who developed an event on an ICI with patients treated with an ICI who did not develop a pericardial event. Cox proportional-hazard model and logistical regression analysis were performed to study the association between ICI use and pericardial disease as well as pericardial disease and mortality. An additional 6-week landmark analysis was performed to account for lead-time bias.ResultsThere were 42 pericardial events in the patients treated with ICI (n=2842) over 193 days (IQR: 64–411), yielding an incidence rate of 1.57 events per 100 person-years. There was a more than fourfold increase in risk of pericarditis or a pericardial effusion among patients on an ICI compared with controls not treated with ICI after adjusting for potential confounders (HR 4.37, 95% CI 2.09 to 9.14, p0.7 mg/kg prednisone) was associated with increased risk of pericardial disease (HR 2.56, 95% CI 1.00 to 6.57, p=0.049).ConclusionsICI use was associated with an increased risk of development of pericardial disease among patients with cancer and a pericardial event on an ICI was associated with a trend towards increase in mortality.

Background Patient limitations guide selection of heart failure therapies, for which indications often specify New York Heart Association Class. Objectives To determine the extent of patient‐reported limitations during daily activities and compare to New York Heart Association class assigned by providers during the same visit, and to left ventricular ejection fraction (LVEF) group. Methods and Results While waiting for their appointment, 948 patients on return visits to an ambulatory HF clinic completed a written questionnaire assessing specific activity limitations, which were compared to physician‐assigned NYHA class during the same visit. Patient‐reported limitation to perform daily activity ranged from 25% for bathing to 61% for yardwork or housework and 71% for jogging or hurrying. Most patients who did not report limitations to perform daily life activities were correctly classified as NYHA I by the physicians (76%), but 12% of the 376 patients classified as NYHA I reported limitations to showering or bathing and 73% reported limitations while doing yardwork or house work. Limitation to walking was reported by 172 patients (50%) classified as class II. Limitations to walking one block were most common in patients with LVEF ≥40% compared to patients with LVEF

A 53-year-old female patient, an active smoker, received a diagnosis in early 2019 of poor-risk, metastatic renal cell carcinoma with invasion of the inferior vena cava and hepatic veins. Pre-treatment transthoracic echocardiography (TTE) revealed thrombotic involvement of the right atrium with

Background Radiotherapy-associated cardiac toxicity studies in patients with locally advanced non–small cell lung cancer (NSCLC) have been limited by small sample size and nonvalidated cardiac endpoints. Objectives The purpose of this analysis was to ascertain whether cardiac radiation dose is a predictor of major adverse cardiac events (MACE) and all-cause mortality (ACM). Methods This retrospective analysis included 748 consecutive locally advanced NSCLC patients treated with thoracic radiotherapy. Fine and Gray and Cox regressions were used to identify predictors for MACE and ACM, adjusting for lung cancer and cardiovascular prognostic factors, including pre-existing coronary heart disease (CHD). Results After a median follow-up of 20.4 months, 77 patients developed ≥1 MACE (2-year cumulative incidence, 5.8%; 95% confidence interval [CI]: 4.3% to 7.7%), and 533 died. Mean radiation dose delivered to the heart (mean heart dose) was associated with a significantly increased risk of MACE (adjusted hazard ratio [HR]: 1.05/Gy; 95% CI: 1.02 to 1.08/Gy; p Conclusions Despite the competing risk of cancer-specific death in locally advanced NSCLC patients, cardiac radiation dose exposure is a modifiable cardiac risk factor for MACE and ACM, supporting the need for early recognition and treatment of cardiovascular events and more stringent avoidance of high cardiac radiotherapy dose.

Background Mechanisms underlying impaired exercise capacity and increased cardiovascular mortality observed in breast cancer (BC) patients remain unclear. The prevalence, functional, and prognostic significance of elevated resting heart rate (HR) and abnormal heart rate recovery (HRR) in breast cancer (BC) requires evaluation. Methods In a single‐center, retrospective, case‐control study of women referred for exercise treadmill testing (ETT), 448 BC patients (62.6 ± 10.0 years) were compared to 448 cancer‐free, age‐matched controls. Elevated resting HR was defined as HR ≥80 bpm at rest. Abnormal HRR at 1‐minute following exercise was defined as ≤12 bpm if active recovery or ≤18 bpm if passive recovery. Association of these parameters with exercise capacity and all‐cause mortality was evaluated. Results Elevated resting HR (23.7% vs 17.0%, P = 0.013) and abnormal HRR (25.9% vs 20.3%, P = 0.048) were more prevalent in BC cohort than controls. In adjusted analyses, BC patients with elevated resting HR (−0.9 METs (SE 0.3); P = 0.0003) or abnormal HRR (−1.3 METs (SE 0.3); P

Purpose of Review Immune checkpoint inhibitors (ICIs) have improved the survival of several cancers. However, they may cause a wide range of immune-related adverse events (irAEs). While most irAEs are manageable with temporary cessation of ICI and immunosuppression, cardiovascular toxicity can be associated with high rates of morbidity and mortality. As ICIs evolve to include high-risk patients with preexisting cardiovascular risk factors and disease, the risk and relevance of ICI-associated cardiotoxicity may be even higher. Recent Findings Several cardiovascular toxicities such as myocarditis, stress cardiomyopathy, and pericardial disease have been reported in association with ICIs. Recent findings also suggest an increased risk of atherosclerosis with ICI use. ICI-associated myocarditis usually occurs early after initiation and can be fulminant. A high index of suspicion is required for timely diagnosis. Prompt treatment with high-dose corticosteroids is shown to improve outcomes. Summary Although the overall incidence is rare, ICI cardiotoxicity, particularly myocarditis, is associated with significant morbidity and mortality, making it a major therapy-limiting adverse event. Early recognition and prompt treatment with the cessation of ICI therapy and initiation of high-dose corticosteroids are crucial to improve outcomes. Cardio-oncologists will need to play an important role not just in the management of acute cardiotoxicity but also to reduce the risk of long-term sequelae.

Despite all available therapies, the rates of hospitalization and death from heart failure (HF) remain unacceptably high. The most common reasons for hospital admission are symptoms related to congestion. During hospitalization, most patients respond well to standard therapy and are discharged with significantly improved symptoms. Post-discharge, many patients receive diligent and frequent follow-up. However, rehospitalization rates remain high. One potential explanation is a persistent failure by clinicians to adequately manage congestion in the outpatient setting. The failure to successfully manage these patients post-discharge may represent an unmet need to improve the way congestion is both recognized and treated. A primary aim of future HF management may be to improve clinical surveillance to prevent and manage chronic fluid overload while simultaneously maximizing the use of evidence-based therapies with proven long-term benefit. Improvement in cardiac function is the ultimate goal and maintenance of a “dry” clinical profile is important to prevent hospital admission and improve prognosis. This paper focuses on methods for monitoring congestion, and strategies for water and sodium management in the context of the complex interplay between the cardiac and renal systems. A rationale for improving recognition and treatment of congestion is also proposed.

International audience; BACKGROUND Myocarditis is a potentially fatal complication of immune checkpoint inhibitor (ICI) therapy. Data on the utility of cardiovascular magnetic resonance (CMR) T1 and T2 mapping in ICI myocarditis are limited.OBJECTIVES This study sought to assess the value of CMR T1 and T2 mapping in patients with ICI myocarditis.METHODS In this retrospective study from an international registry of patients with ICI myocarditis, clinical and CMR findings (including T1 and T2 maps) were collected. Abnormal T1 and T2 were defined as 2 SD above site (vendor/field strength specific) reference values and a z-score was calculated for each patient. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block.RESULTS Of 136 patients with ICI myocarditis with a CMR, 86 (63%) had T1 maps and 79 (58%) also had T2 maps. Among the 86 patients (66.3 +/- 13.1 years of age), 36 (41.9%) had a left ventricular ejection fraction

PURPOSE/OBJECTIVE(S) Left anterior descending (LAD) coronary artery volume receiving 15 Gy (V15 Gy) ≥10% and left circumflex (LCX) V15 Gy ≥14% are associated with an increased risk of major adverse cardiac events (MACE), while LAD V15 Gy ≥10% can significantly increase the risk of mortality in patients with non-small cell lung cancer (NSCLC). Given that reduction of coronary dose is a modifiable risk factor during RT planning, we identified absolute critical volume (vol) thresholds of left coronary artery (LCA) exposure to 15 Gy that predict for MACE and all-cause mortality (ACM). MATERIALS/METHODS Retrospective analysis of 701 patients with locally advanced NSCLC treated with RT between 2003 and 2014. Coronary arteries were manually segmented with an 8-mm brush size. The absolute vol (cc) of LAD, LCX, or LCA (combined LAD+LCX) structures receiving ≥15 Gy were calculated. Area under the receiver operating curve (AUC) and cut-point analyses estimating MACE (unstable angina, heart failure, myocardial infarction, coronary revascularization, and cardiac death) were performed. Fine and Gray and Cox regressions were performed, adjusting for pre-existing coronary heart disease (CHD) and other cardiovascular and cancer prognostics factors. RESULTS The median age was 65 years (interquartile range, 57-73 years) and 50.8% (n = 356) were men. The optimal cut-point (C-index) for the absolute vol. receiving ≥15 Gy for the LAD, LCX, and LCA was ≥1.1 cc (0.63), ≥1.3 cc (0.65), and ≥2.6 cc (0.64), respectively. Adjusting for baseline CHD and other factors, there was an increased risk of MACE with an LAD V15 Gy vol. ≥1.1 cc (adjusted hazard ratio [AHR], 7.59; 95% confidence interval [CI], 2.24-25.69; P = 0.001), an LCX V15 Gy vol. ≥1.3 cc (AHR, 8.24; 95% CI, 2.84-23.90; P 0.05). Specifically, the 2-year ACM estimates in CHD-negative patients for LAD V15 Gy vol. (≥1.1 vs. < 1.1 cc) was 50.9% vs. 42.3%, and for LCA V15 Gy vol. (≥2.6 vs. < 2.6 cc) was 51.1% vs. 43.0%, respectively (P for interaction ≤.01). CONCLUSION Critical volume thresholds of 15 Gy for the LAD and LCA were independent predictors of MACE and ACM, particularly in patients without CHD. These constraints may help inform RT planning by guiding LCA dose reduction and identify patients who may benefit most from advanced RT techniques to mitigate excess cardiac risk.

PURPOSE/OBJECTIVE(S) Thoracic radiotherapy (TRT) is a mainstay treatment for locally advanced non-small cell lung cancer (LA-NSCLC). Mean heart dose (MHD) and left anterior descending (LAD) receiving ≥15 Gy (LADV15) was shown to predict major adverse cardiac events (MACE) in LA-NSCLC patients receiving TRT. We aim to develop a clinically applicable MACE risk prediction score model, including both cardiac dosimetric and baseline risk factors. MATERIALS/METHODS Retrospective data from 748 consecutive patients with LA-NSCLC treated with curative intent between November 1998 to December 2013 were included. The data was split based on diagnosis dates to allow external validation. Model development was performed on 500 consecutive patients diagnosed before December 2010 using multivariable Cox-proportional hazard model; backward elimination scheme (α = 0.05) was used to select the predictors for the final model. Potential predictors were selected a priori based on prior literature: age, pre-existing coronary heart disease (CHD), Framingham Risk, hypertension (HTN), MHD, LADV15, intensity modulated RT (IMRT) use, and interaction between CHD and LADV15 (CHD:LADV15). Model performance was assessed by the Harrell's c-index and internally validated using leave-one out cross validation (LOOCV). The model was applied to the remaining 248 consecutive patients from the initial cohort as the external validation "test" dataset. RESULTS The development and test cohorts had median age 64 vs 66 years (P = 0.02), 51.0 vs. 50.4% females (P = 0.88), and 89.4 vs 89.1% stage III cancer (P = 0.91). The final model incorporated CHD, HTN, LADV15, and CHD:LADV15 (β coefficients: 2.703, 1.129, 0.043, -0.047; all P < 0.001; c-index 0.773). LOOCV Pseudo R2 = 0.0195. The c-index on the external test dataset was 0.727. Actuarial 3-year MACE rates were 10.7% for development cohort and 15.4% for test cohort. Stratifying development cohort patients into terciles based on MACE risk prediction scores yielded 3-year MACE rates of 0%, 5.7%, and 25.6% for lowest to highest risk-terciles, respectively; among test cohort, the 3-year MACE rates were 4.9%, 10.5%, and 31.9%. Respectively, the 3-year overall survival rates for lowest to highest MACE risk-terciles were 47.3%, 35.2%, and 32.8% among development cohort, and 52.3%, 43.9% and 30.6% within test cohort (both Log-rank P < 0.05). CONCLUSION The 3-year MACE rates spans 5% to 32% from lowest to highest risk groups. Both LADV15 and pre-existing cardiac risk factors are important in predicting MACE risk post-TRT. MACE risk score was associated with survival. This tool has the potential to estimate personalized LADV15 constraints based on patient risk factors and acceptable MACE risk thresholds (e.g., 5-10%), thus may help identify patients who may benefit most from the application of advanced RT techniques to further reduce LAD dose as a modifiable risk factor during RT planning.

Background: Surgical aortic valve replacement (SAVR) is associated with adverse outcomes in patients with radiation-associated aortic stenosis. Transcatheter aortic valve replacement (TAVR) may improve outcomes in this population. Methods: We evaluated 1668 TAVR and 2611 patients with SAVR enrolled in the Society of Thoracic Surgeons’ database between 2011 and 2018. Multiple logistic regression was used to compare 30- day outcomes between TAVR and SAVR. Propensity-matched analysis was performed to confirm results of the overall cohort. Additionally, the cohort was stratified into early (2011–2014) versus contemporary (2015–2018) TAVR eras, and 30-day outcomes for TAVR and SAVR were compared. Finally, outcomes with transfemoral TAVR versus SAVR were compared. Results: In the overall cohort, TAVR was associated with significantly reduced 30-day mortality (odds ratio [OR] TAVR/SAVR =0.60 [0.40–0.91]). Postoperative atrial fibrillation, pneumonia, pleural effusion, renal failure, and bleeding also occurred less frequently with TAVR. Stroke/transient ischemic attack (TIA; OR TAVR/SAVR , 2.03 [1.09–3.77]) and pacemaker implantation (OR TAVR/SAVR , 1.62 [1.21–2.17]) were higher with TAVR. Propensity-matched analysis yielded similar results as the overall cohort. Following stratification by era, TAVR versus SAVR was associated with reduced 30-day mortality in the contemporary but not early era (OR Early , 0.78 [0.48–1.28]; OR Contemporary , 0.31 [0.14–0.65]). Pacemaker implantation was higher with TAVR versus SAVR in both eras (OR Early , 1.60 [1.03–2.46]; OR Contemporary , 1.64 [1.10–2.45]). There was also a nonsignificant trend towards increased stroke/TIA with TAVR during both eras (OR Early , 1.39 [0.58–3.36]; OR Contemporary , 2.46 [0.99–6.10]). Finally, transfemoral TAVR (N=1369) versus SAVR revealed similar findings as the overall cohort; however, the association of TAVR with stroke/TIA was not statistically significant (OR Stroke/TIA , 1.57 [0.79–3.09]). Conclusions: TAVR provides an effective and evolving alternative to SAVR for radiation-associated severe aortic stenosis and was associated with lower 30-day mortality and postoperative complications. TAVR was associated with increased pacemaker implantation and a trend towards increased stroke/TIA. In this unique population with extensive valvular and vascular calcifications, the risk of stroke/TIA with TAVR requires careful consideration and further investigation.

Background Myocarditis attributable to immune checkpoint inhibitor (ICI) therapy is a potentially fatal immune‐related adverse event. Limited data have suggested an association between baseline and on‐treatment absolute lymphocyte count (ALC) and neutrophil/lymphocyte ratio (NLR) and the development of other immune‐related adverse events; there are no data characterizing the role of ALC and NLR in ICI‐associated myocarditis. Methods and Results This was a case control study of 55 patients with ICI myocarditis and 55 controls without any post‐ICI immune‐related adverse events. We leveraged clinical testing, where patients underwent routine serial blood counts before and with each ICI cycle to compare the baseline and change in ALC and NLR between cases and controls. The association between the change in these parameters with clinical variables and major adverse cardiac events was also tested. In cases, there was a statistically significant decrease in ALC with myocarditis from baseline (1.6 thousands per cubic milliliter (K/μL); interquartile range, 1.1–1.9 K/μL) to admission (1.1 K/μL; interquartile range, 0.7–1.3 K/μL; P P P P =0.019) were associated with major adverse cardiac events. Conclusions A reduction in ALC and an increase in NLR was seen with ICI myocarditis. A greater decrease in ALC or increase in NLR was associated with subsequent major adverse cardiac events.

Saroglitazar, a dual peroxisome proliferator activated receptor α/γ agonist, approved for diabetic dyslipidemia (DD), is potential therapeutic option for non-alcoholic fatty liver disease (NAFLD). This prospective, observational, real-world study aimed to determine efficacy and safety of Saroglitazar in patients with NAFLD and DD. We included patients with DD and NAFLD who received Saroglitazar 4 mg once daily for 24 weeks. Blood investigations, liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) (FibroScan) were compared at baseline and 24 weeks. Of 163 patients screened, 107 were included, and 101 completed 24 weeks treatment (mean age 50.4 ± 12.3 years, 78.5% males, mean body mass index 28.8 ± 4.2). After 24 weeks, alanine transaminase (ALT) reduced significantly from 94 (47–122) to 39 (31–49) (p p p = 0.0261). CAP, glycated hemoglobin and lipid parameters also improved significantly. On linear regression, there was significant association between percent change in ALT and AST with TG reduction after treatment (p = 0.024 and 0.037 respectively).We conclude that Saroglitazar leads to significant improvement in transaminases, LSM, and CAP in NAFLD patients with DD.

When the COVID-19 pandemic began, formal frameworks to collect data about affected patients were lacking. The COVID-19 and Cancer Consortium (CCC19) was formed to collect granular data on patients with cancer and COVID-19 at scale and as rapidly as possible. CCC19 has grown from five initial institutions to 125 institutions with >400 collaborators. More than 5,000 cases with complete baseline data have been accrued. Future directions include increased electronic health record integration for direct data ingestion, expansion to additional domestic and international sites, more intentional patient involvement, and granular analyses of still-unanswered questions related to cancer subtypes and treatments.

Background Influenza vaccination (FV) is recommended for patients with cancer. Recent data suggested that the administration of the FV was associated with an increase in immune-related adverse events (irAEs) among patients on immune checkpoint inhibitors (ICIs). Myocarditis is an uncommon but serious complication of ICIs and may also result from infection with influenza. There are no data testing the relationship between FV and the development of myocarditis on ICIs. Methods Patients on ICIs who developed myocarditis (n = 101) (cases) were compared to ICI-treated patients (n = 201) without myocarditis (controls). A patient was defined as having the FV if they were administered the FV from 6 months prior to start of ICI to anytime during ICI therapy. Alternate thresholds for FV status were also tested. The primary comparison of interest was the rate of FV between cases and controls. Patients with myocarditis were followed for major adverse cardiac events (MACE), defined as the composite of cardiogenic shock, cardiac arrest, hemodynamically significant complete heart block and cardiovascular death. Results The FV was administered to 25% of the myocarditis cases compared to 40% of the non-myocarditis ICI-treated controls (p = 0.01). Similar findings of lower rates of FV administration were noted among myocarditis cases when alternate thresholds were tested. Among the myocarditis cases, those who were vaccinated had 3-fold lower troponin levels when compared to unvaccinated cases (FV vs. No FV: 0.12 [0.02, 0.47] vs. 0.40 [0.11, 1.26] ng/ml, p = 0.02). Within myocarditis cases, those administered the FV also had a lower rate of other irAEs when compared to unvaccinated cases (36 vs. 55% p = 0.10) including lower rates of pneumonitis (12 vs. 36%, p = 0.03). During follow-up (175 [IQR 89, 363] days), 47% of myocarditis cases experienced a MACE. Myocarditis cases who received the FV were at a lower risk of cumulative MACE when compared to unvaccinated cases (24 vs. 59%, p = 0.002). Conclusion The rate of FV among ICI-related myocarditis cases was lower than controls on ICIs who did not develop myocarditis. In those who developed myocarditis related to an ICI, there was less myocardial injury and a lower risk of MACE among those who were administered the FV. Electronic supplementary material The online version of this article (10.1186/s40425-019-0535-y) contains supplementary material, which is available to authorized users.

Myocarditis is a rare but potentially fatal complication of immune checkpoint inhibitors (ICI). Among broad populations, late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) is used for diagnosis and risk prediction in patients with myocarditis. There are no data on the use

Myocarditis is a serious and poorly characterized complication from immune checkpoint inhibitors (ICIs). Global longitudinal strain (GLS) is a sensitive marker of cardiac toxicity among patients receiving chemotherapy. There are no data on the use of GLS in ICI myocarditis. We compared

Introduction: Myocarditis due to immune checkpoint inhibitor (ICI) therapy is a potentially fatal immune-related adverse event (irAE). Hypothesis: Limited data have suggested an association between baseline and on-treatment absolute lymphocyte count (ALC) and neutrophil lymphocyte ratio (NLR) and the development of other irAEs; there are no data characterizing the role of ALC and NLR in ICI-associated myocarditis. Methods: This was a case control study of 55 patients with ICI myocarditis and 55 controls without any post-ICI irAEs. We leveraged clinical testing where patients underwent routine serial blood counts before and with each ICI cycle to compare the baseline and change in ALC and NLR between cases and controls. The association between the change in these parameters with clinical variables and major adverse cardiac events (MACE) was also tested. Results: In those who developed myocarditis, there was a decrease in ALC from baseline (1.6 K/μL, IQR 1.1-1.9) to admission (1.1 K/μL, IQR 0.7-1.3, p Conclusions: A reduction in ALC and an increase in NLR was seen with ICI myocarditis. A greater decrease in ALC or increase in NLR were associated with subsequent MACE.

Background Atrial fibrillation (AF) is the most common arrhythmia in patients with cancer. Management of AF in patients with cancer poses unique challenges. Long-term use of antiarrhythmic drug (AAD) therapy lacks evidence of efficacy in this population and poses risk of drug interactions. Catheter ablation is a well-established treatment modality for AAD resistant symptomatic AF and in patients with heart failure. Nevertheless, the effectiveness and safety of catheter ablation in patients with cancer is not well established. Method We retrospectively analyzed consecutive patients who underwent catheter ablation for AF, with either history of cancer (other than non-melanoma skin cancer) within 5-years prior or exposure to systemic anthracycline and/or thoracic radiation therapy at any time. Results The study included 162 patients. The mean age was 65.5 (26–84 years) years and 50% were female. Overall 133 (82%) patients had freedom from AF at 12 months following ablation. Of these 74 (54%) required post-ablation AAD, 18 (13.5%) required another ablation within the first 12 months and 9 (6.7%) required both AAD and a second ablation to maintain sinus rhythm. There were 14 adverse events (8.6%); 5 access site and 4 non-access site bleeding, 2 strokes, 2 cardiac tamponade and 1 pulmonary vein stenosis with ≈1% serious complications. Conclusion The success of catheter ablation for AF and the incidence of procedure related complications in patients with a history of recent cancer or prior exposure to cardiotoxic therapies are similar to that reported in patients without a history of cancer and hence if needed, it should be considered in select patients. Funding Acknowledgement Type of funding source: Private hospital(s). Main funding source(s): Dr. S Ganatra is supported by Lahey Physician Research Stipend Program.