Search

Women with HIV (WWH) have heightened heart failure risk. Plasma OPN (osteopontin) is a powerful predictor of heart failure outcomes in the general population. Limited data exist on relationships between plasma OPN and surrogates of HIV-associated heart failure risk.Prospective, cross-sectional.We analyzed relationships between plasma OPN and cardiac structure/function (assessed using cardiovascular magnetic resonance imaging) and immune activation (biomarkers and flow cytometry) among 20 WWH and 14 women without HIV (WWOH).Plasma OPN did not differ between groups. Among WWH, plasma OPN related directly to the markers of cardiac fibrosis, growth differentiation factor-15 (ρ = 0.51, P = 0.02) and soluble interleukin 1 receptor-like 1 (ρ = 0.45, P = 0.0459). Among WWH (but not among WWOH or the whole group), plasma OPN related directly to both myocardial fibrosis (ρ = 0.49, P = 0.03) and myocardial steatosis (ρ = 0.46, P = 0.0487). Among the whole group and WWH (and not among WWOH), plasma OPN related directly to the surface expression of C-X3-C motif chemokine receptor 1 (CX3CR1) on nonclassical (CD14-CD16+) monocytes (whole group: ρ = 0.36, P = 0.04; WWH: ρ = 0.46, P = 0.04). Further, among WWH and WWOH (and not among the whole group), plasma OPN related directly to the surface expression of CC motif chemokine receptor 2 (CCR2) on inflammatory (CD14+CD16+) monocytes (WWH: ρ = 0.54, P = 0.01; WWOH: ρ = 0.60, P = 0.03), and in WWH, this held even after controlling for HIV-specific parameters.Among WWH, plasma OPN, a powerful predictor of heart failure outcomes, related to myocardial fibrosis and steatosis and the expression of CCR2 and CX3CR1 on select monocyte subpopulations. OPN may play a role in heart failure pathogenesis among WWH.NCT02874703.

Global circumferential strain (GCS) and global radial strain (GRS) are reduced with cytotoxic chemotherapy. There are limited data on the effect of immune checkpoint inhibitor (ICI) myocarditis on GCS and GRS.This study aimed to detail the role of GCS and GRS in ICI myocarditis.In this retrospective study, GCS and GRS from 75 cases of patients with ICI myocarditis and 50 ICI-treated patients without myocarditis (controls) were compared. Pre-ICI GCS and GRS were available for 12 cases and 50 controls. Measurements were performed in a core laboratory blinded to group and time. Major adverse cardiovascular events (MACEs) were defined as a composite of cardiogenic shock, cardiac arrest, complete heart block, and cardiac death.Cases and controls were similar in age (66 ± 15 years vs 63 ± 12 years; P = 0.20), sex (male: 73% vs 61%; P = 0.20) and cancer type (P = 0.08). Pre-ICI GCS and GRS were also similar (GCS: 22.6% ± 3.4% vs 23.5% ± 3.8%; P = 0.14; GRS: 45.5% ± 6.2% vs 43.6% ± 8.8%; P = 0.24). Overall, 56% (n=42) of patients with myocarditis presented with preserved left ventricular ejection fraction (LVEF). GCS and GRS were lower in myocarditis compared with on-ICI controls (GCS: 17.5% ± 4.2% vs 23.6% ± 3.0%; P< 0.001; GRS: 28.6% ± 6.7% vs 47.0% ± 7.4%; P< 0.001). Over a median follow-up of 30days, 28 cardiovascular events occurred. A GCS (HR: 4.9 [95%CI: 1.6-15.0]; P = 0.005) and GRS (HR: 3.9 [95%CI: 1.4-10.8]; P = 0.008) below the median was associated with an increased event rate. In receiver-operating characteristic (ROC) curves, GCS (AUC: 0.80 [95%CI: 0.70-0.91]) and GRS (AUC: 0.76 [95%CI: 0.64-0.88]) showed better performance than cardiac troponin T (cTnT) (AUC: 0.70 [95%CI: 0.58-0.82]), LVEF (AUC: 0.69 [95%CI: 0.56-0.81]), and age (AUC: 0.54 [95%CI: 0.40-0.68]). Net reclassification index and integrated discrimination improvement demonstrated incremental prognostic utility of GRS over LVEF (P = 0.04) and GCS over cTnT (P = 0.002).GCS and GRS are lower in ICI myocarditis, and the magnitude of reduction has prognostic significance.

Conventional photon radiation therapy (RT) for breast cancer is associated with a reduction in global longitudinal strain (GLS) and an increase in troponin, N-terminal pro hormone B-type natriuretic peptide (NT-proBNP), and incident heart failure. The cardiac radiation exposure with proton-RT is much reduced and thus may be associated with less cardiotoxicity. The objective was to test the effect of proton-RT on GLS, troponin, and NT-proBNP.We conducted a prospective, observational, single-center study of 70 women being treated with proton-RT for breast cancer. Serial measurements of GLS, high-sensitivity troponin I, and NT-proBNP were performed at prespecified intervals (before proton-RT, 4 weeks after completion of proton-RT, and again at 2 months after proton-RT).The mean age of the patients was 46 ± 11 years, and the mean body mass index was 25.6 ± 5.2 kg/mProton-RT did not affect LV function and was not associated with an increase in biomarkers. These data support the potential cardiac benefits of proton-RT compared with conventional RT.

OBJECTIVE: Women with HIV (WHIV) on antiretroviral therapy (ART) face an increased risk of cardiovascular disease (CVD) in the context of heightened systemic immune activation. Aortic stiffness, a measure of vascular dysfunction and a robust predictor of CVD outcomes, is highly influenced by immune activation. We compared aortic stiffness among women with and without HIV and examined interrelationships between aortic stiffness and key indices of systemic immune activation. METHODS: Twenty WHIV on ART and 14 women without HIV group-matched on age and body mass index (BMI) were prospectively recruited and underwent cardiovascular magnetic resonance imaging, as well as metabolic and immune phenotyping. RESULTS: Age and BMI did not differ significantly across groups (age: 52 ± 4 vs. 53 ± 6 years; BMI: 32 ± 7 vs. 32 ± 7 kg/m(2)). Aortic pulse wave velocity (aPWV) was higher among WHIV (8.6 ± 1.3 vs. 6.5 ± 1.3 m/s, P < 0.0001), reflecting increased aortic stiffness. Among the whole group and among WHIV, aPWV related to sCD163 levels (whole group: R = 0.65, P < 0.0001; WHIV: R = 0.73, P = 0.0003) and to myocardial fibrosis (extracellular volume; whole group: R = 0.54, P = 0.001; WHIV: R = 0.47, P = 0.04). Both HIV status and sCD163 levels independently predicted aPWV, controlling for age, BMI, cigarette smoking status, and systolic blood pressure (HIV status: β-estimate = 0.69, 95% CI [0.1 to 1.3], P = 0.02; sCD163: β-estimate = 0.002, 95% CI [0.0006 to 0.004], P = 0.01). Among WHIV, sCD163 levels independently predicted aPWV, controlling for duration of HIV, CD4 count, and HIV viral load (sCD163: β-estimate = 0.004, 95% CI [0.002 to 0.005], P = 0.0005). CONCLUSIONS: Asymptomatic WHIV on ART have increased aortic stiffness as compared to matched control subjects. Among WHIV, aPWV related to heightened monocyte activation (sCD163) and to downstream CVD pathology (myocardial fibrosis). CLINICALTRIALS.GOV REGISTRATION: NCT02874703.

Background People with human immunodeficiency virus (PWH) face increased risks for heart failure and adverse heart failure outcomes. Myocardial steatosis predisposes to diastolic dysfunction, a heart failure precursor. We aimed to characterize myocardial steatosis and associated potential risk factors among a subset of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) participants. Methods Eighty-two PWH without known heart failure successfully underwent cardiovascular magnetic resonance spectroscopy, yielding data on intramyocardial triglyceride (IMTG) content (a continuous marker for myocardial steatosis extent). Logistic regression models were applied to investigate associations between select clinical characteristics and odds of increased or markedly increased IMTG content. Results Median (Q1, Q3) IMTG content was 0.59% (0.28%, 1.15%). IMTG content was increased (> 0.5%) among 52% and markedly increased (> 1.5%) among 22% of participants. Parameters associated with increased IMTG content included age (P = .013), body mass index (BMI) ≥ 25 kg/m2 (P = .055), history of intravenous drug use (IVDU) (P = .033), and nadir CD4 count Conclusions A substantial proportion of antiretroviral therapy–treated PWH exhibited myocardial steatosis. Age, BMI ≥ 25 kg/m2, low nadir CD4 count, and history of IVDU emerged as possible risk factors for myocardial steatosis in this group. Clinical Trials Registration NCT02344290; NCT03238755.

Introduction: Myocarditis is as a major immune-related adverse event following the use of immune checkpoint inhibitors (ICI). Global radial strain (GRS) reflects both longitudinal and circumferential fiber shortening but no data exist regarding its utility for diagnosis and risk stratification of ICI-myocarditis. Hypothesis: We hypothesized that GRS from echocardiography data would be reduced in patients with ICI-myocarditis and its reduction would have prognostic implications. Methods: Leveraging a multicenter international registry, we measured GRS from 76 patients with myocarditis and 49 ICI treated patients with no myocarditis. Pre-ICI GRS values were available for 10 cases and 38 controls. Measures were performed in a central laboratory blinded to group and time (TomTec, Germany). Major adverse cardiac event was a composite of cardiogenic shock, cardiac arrest, complete heart block and cardiac death. Results: Groups had similar age (66±15 vs. 63±12 years; p=0.20), sex distribution (male: 72% vs. 61%; p= 0.27) and cancer type (p=0.07). Pre-ICI GRS values were similar between cases and controls (47.4±2.9 vs. 45.4±6.0; p=0.12). A total of 57% of myocarditis patients had LVEF of >50% at presentation. The GRS was lower in patients with myocarditis compared with controls (28.6±6.7 vs. 47±7.4; p Conclusions: Global radial strain is lower in ICI- myocarditis and the magnitude of the reduction is associated with a higher rate of events.

Background Chimeric antigen receptors redirect T cells (CAR-T) to target cancer cells. There are limited data characterizing cardiac toxicity and cardiovascular (CV) events among adults treated with CAR-T. Objectives The purpose of this study was to evaluate the possible cardiac toxicities of CAR-T. Methods The registry included 137 patients who received CAR-T. Covariates included the occurrence and grade of cytokine release syndrome (CRS) and the administration of tocilizumab for CRS. Cardiac toxicity was defined as a decrease in the left ventricular ejection fraction or an increase in serum troponin. Cardiovascular events were a composite of arrhythmias, decompensated heart failure, and CV death. Results The median age was 62 years (interquartile range [IQR]: 54 to 70 years), 67% were male, 88% had lymphoma, and 8% had myeloma. Approximately 50% were treated with commercial CAR-T (Yescarta or Kymriah), and the remainder received noncommercial products. CRS, occurring a median of 5 days (IQR: 2 to 7 days) after CAR-T, occurred in 59%, and 39% were grade ≥2. Tocilizumab was administered to 56 patients (41%) with CRS, at a median of 27 h (IQR: 16 to 48 h) after onset. An elevated troponin occurred in 29 of 53 tested patients (54%), and a decreased left ventricular ejection fraction in 8 of 29 (28%); each occurred only in patients with grade ≥2 CRS. There were 17 CV events (12%, 6 CV deaths, 6 decompensated heart failure, and 5 arrhythmias; median time to event of 21 days), all occurred with grade ≥2 CRS (31% patients with grade ≥2 CRS), and 95% of events occurred after an elevated troponin. The duration between CRS onset and tocilizumab administration was associated with CV events, where the risk increased 1.7-fold with each 12-h delay to tocilizumab. Conclusions Among adults, cardiac injury and CV events are common post–CAR-T. There was a graded relationship among CRS, elevated troponin, and CV events, and a shorter time from CRS onset to tocilizumab was associated with a lower rate of CV events.

Objectives The aim of this study was to determine the incidence of sudden cardiac death (SCD) among persons living with human immunodeficiency virus infection (PHIV) with heart failure (HF), who were hospitalized for HF, and the risk factors associated with it. Background HF is associated with an increased risk for SCD. PHIV are at heightened risk for HF. Methods This was a retrospective study of 2,578 patients hospitalized with HF from a single academic center, of whom 344 were PHIV. The outcome of interest was SCD. Subgroup analyses were performed by strata of viral load (VL) and left ventricular ejection fraction (LVEF) Results Of 2,578 patients with HF, 2,149 (86%) did not have implantable cardioverter-defibrillators; of these, there were 344 PHIV and 1,805 uninfected control subjects. Among PHIV with HF, 313 (91%) were prescribed antiretroviral therapy and 64% were virally suppressed. There were 191 SCDs over a median follow-up period of 19 months. Compared with control subjects, PHIV had a 3-fold increase in SCD (21.0% vs. 6.4%; adjusted odds ratio: 3.0; 95% confidence interval: 1.78 to 4.24). Among PHIV, cocaine use, lower LVEF, absence of beta-blocker prescription, and VL were predictors of SCD. The SCD rate among PHIV with undetectable VL was similar to the rate among uninfected subjects. Similar findings were observed by LVEF strata. Among PHIV with HF without conventional indications for an implantable cardioverter-defibrillator, the rate of SCD was 10% per year. Conclusions PHIV hospitalized with HF are at a markedly increased risk for SCD. SCD risk was increased in patients with lower LVEFs, lower CD4 counts, and higher VL.

Context Women with HIV (WHIV) on anti-retroviral therapy (ART) are living longer but facing heightened vulnerability to heart failure. Objective We investigated metabolic/hormonal/immune parameters relating to diastolic dysfunction—a precursor to heart failure—among WHIV without known cardiovascular disease (CVD). Design and Outcome Measures Nineteen ART-treated WHIV and 11 non-HIV-infected women without known CVD enrolled and successfully completed relevant study procedures [cardiac magnetic resonance spectroscopy (MRS) and cardiac MRI]. Groups were matched on age and body mass index. Primary outcome measures included intramyocardial triglyceride content (cardiac MRS) and diastolic function (cardiac MRI). Relationships between intramyocardial triglyceride content and clinical parameters were also assessed. Results Among WHIV (vs non-HIV-infected women), intramyocardial triglyceride content was threefold higher [1.2 (0.4, 3.1) vs 0.4 (0.1, 0.5)%, P = 0.01], and diastolic function was reduced (left atrial passive ejection fraction: 27.2 ± 9.6 vs 35.9 ± 6.4%, P = 0.007). There was a strong inverse relationship between intramyocardial triglyceride content and diastolic function (ρ = −0.62, P = 0.004). Among the whole group, intramyocardial triglyceride content did not relate to chronologic age but did increase across the reproductive aging spectrum (P = 0.02). HIV status and reproductive aging status remained independent predictors of intramyocardial triglyceride content after adjusting for relevant cardiometabolic parameters (overall model R2 = 0.56, P = 0.003; HIV status P = 0.01, reproductive aging status P = 0.02). Conclusions For asymptomatic WHIV, increased intramyocardial triglyceride content is associated with diastolic dysfunction. Moreover, relationships between intramyocardial triglyceride accumulation and women’s reproductive aging are noted.

Persons living with HIV (PLHIV) have an increased risk of heart failure (HF). However, little is known about outcomes among PLHIV with HF. The study aim was to compare HF outcomes among PLHIV with HF versus individuals without HIV with HF.Our cohort included 2,308 individuals admitted with decompensated HF. We compared baseline characteristics, 30-day HF readmission, and cardiovascular (CV) and all-cause mortality. Within PLHIV, we assessed outcomes stratified between CD4 count and viral load (VL), and tested the association between traditional and HIV-specific parameters with 30-day HF readmission.There were 374 (16%) PLHIV with HF. Among PLHIV, 92% were on antiretroviral therapy and 63% had a VL200 copies/mL. Groups were similar with respect to age, sex, race/ethnicity, and CV risk factors. In follow-up, PLHIV had increased 30-day HF readmission (49% vs 32%) and CV (26% vs 13.5%) and all-cause mortality rates (38% vs 22%). Among PLHIV, cocaine use, HIV-specific parameters (CD4, VL), and coronary artery disease were predictors of 30-day HF readmission. Specifically, among PLHIV, those with detectable VL had higher 30-day HF readmission and CV mortality, whereas PLHIV with undetectable VL had a similar 30-day HF readmission rate and CV mortality to uninfected controls with HF. Similar outcomes were observed across strata of left ventricular ejection fraction and by CD4.PLHIV with a low CD4 count or detectable VL have an increased 30-day HF readmission rate as well as increased CV and all-cause mortality. In contrast, PLHIV with a higher CD4 count and undetectable VL have similar HF outcomes to uninfected controls.

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

Women with HIV (WWH) transitioning through menopause have heightened cardiovascular disease (CVD) risk. In the general population, hot flash burden relates to CVD risk indices. We found higher hot flash burden among women with vs without HIV. Further, among WWH, hot flash burden related to select CVD risk indices.ClinicalTrials.gov RegistrationNCT02874703.

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 Radiation therapy for head and neck cancer (HNC) associates with an increase in cerebrovascular events. Amygdalar metabolic activity (AmygA), a measure of stress-associated neurobiological activity, associates with cardiovascular events in patients without cancer. In this study, we tested whether AmygA was associated with cerebrovascular events among patients treated with radiation therapy. Methods The associations between AmygA (at cancer staging) and subsequent cerebrovascular events as well as inflammatory biomarkers and arterial inflammation, were tested among consecutive patients with HNC treated with radiation therapy who underwent 18F-FDG-PET/CT. Results Among 240 patients (59±13 years; 30% female, 48% had stage 4 disease), there were 26 events over a median follow-up period of 3 years (IQR: 1.7–5.1). AmygA at cancer staging was associated with subsequent cerebrovascular events, an effect that remained significant after adjustment for age, sex, and cerebrovascular risk factors (adjusted hazard ratio 1.47, 95% CI 1.04–2.09, P=0.031). The association persisted when the analysis was restricted to patients with no prior history of CV disease and even among those with lower predicted CV risk (P Conclusions Amygdalar activity, a quantifiable biomarker of stress-associated brain activity, associated with subsequent cerebrovascular events among patients with cancer treated with radiation therapy. Funding Acknowledgement Type of funding source: None

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.

Recent advances in cancer treatments have significantly improved survival rates, reemphasizing the focus on reducing the potential complications associated with some therapies. Cardiovascular disease associated with chemotherapies is a major cause of morbidity and mortality in cancer survivors. Early detection of cardiotoxicity improves cardiac outcomes among cancer patients. The review will focus on imaging modalities used to assess cardiotoxicity - the cardiovascular consequences of chemotherapies. The review will discuss the benefits and limitations associated with each technique, as well as the guidelines available to help identify at risk patients. We will discuss novel techniques that may help detect earlier signs of cardiotoxicity, directing management that may improve clinical outcomes.Published by Elsevier Inc.

Background Incident heart failure (HF) is increased in persons with human immunodeficiency virus (PHIV). Protease inhibitors (PIs) are associated with adverse cardiac remodeling and vascular events; however, there are no data on the use of PIs in PHIV with HF. Objectives This study sought to compare characteristics, cardiac structure, and outcomes in PHIV with HF who were receiving PI-based versus non-PI (NPI) therapy. Methods This was a retrospective single-center study of all 394 antiretroviral therapy–treated PHIV who were hospitalized with HF in 2011, stratified by PI and NPI. The primary outcome was cardiovascular (CV) mortality, and the secondary outcome was 30-day HF readmission rate. Results Of the 394 PHIV with HF (47% female, mean age 60 ± 9.5 years, CD4 count 292 ± 206 cells/mm3), 145 (37%) were prescribed a PI, whereas 249 (63%) were prescribed NPI regimens. All PI-based antiretroviral therapy contained boosted-dose ritonavir. PHIV who were receiving a PI had higher rates of hyperlipidemia, diabetes mellitus, and coronary artery disease (CAD); higher pulmonary artery systolic pressure (PASP); and lower left ventricular ejection fraction. In follow-up, PI use was associated with increased CV mortality (35% vs. 17%; p Conclusions PI-based regimens in PHIV with HF are associated with dyslipidemia, diabetes, CAD, a lower left ventricular ejection fraction, and a higher PASP. In follow-up, PHIV with HF who are receiving a PI have increased CV mortality and 30-day HF readmission.

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 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.

Background: Women with HIV (WWH) (vs. women without HIV) have an increased risk of cardiovascular disease (CVD) in relation to heightened systemic immune activation/inflammation. Moreover, WWH show evidence of advanced reproductive aging and unique patterns of hot flash symptomatology. General population studies have revealed that hot flashes may relate to surrogate markers of CVD risk. The relationship between hot flashes and immune activation as well as subclinical cardiac pathology among WWH has not been previously investigated. Methods: In a prospective, cross-sectional study, 23 WWH on anti-retroviral therapy and 19 women without HIV (ages 40–75), group-matched on age and BMI, were enrolled and completed reproductive health assessments, immune phenotyping and cardiovascular MRI. Women without prior CVD or diabetes were eligible. Results: Women were similar in age and BMI (WWH vs. women without HIV: 51 ± 5 vs. 52 ± 6 years, P=0.79 and 32 ± 8 vs. 31 ± 7 kg/m2, P=0.71). There was no significant between-group difference in the percentage of women without menses in the past year (p=0.52) or in the percentage of women with undetectable levels of anti-mullerian hormone (p=0.71). No women in either group were on estrogen and/or progesterone for treatment of menopausal symptoms. Hot flash frequency (days per week with hot flashes) was higher among WWH versus women without HIV (median [IQR], 7.0 [1.3, 7.0] vs. 0.8 [0.0, 2.1], p=0.01). In sensitivity analyses excluding either women with menses in the past year or with detectable AMH, WWH still reported a significantly higher number of days per week with hot flashes (7.0 [6.3, 7.0] vs. 0.4 [0.0, 2.3], p=0.007, and 7.0 [2.4, 7.0] vs. 0.8 [0.0, 2.1], p=0.01, respectively). Among WWH experiencing (vs. not experiencing) hot flashes in the past year, longer duration of ART use was noted (21.2 [16.0, 22.7] vs. 9.3 [3.3, 16.0] years, p=0.03). Among the entire cohort and among WWH, women with more than one hot flash per day had higher levels of soluble CD14, a marker of monocyte activation, compared to women with one or fewer hot flash per day (p=0.004 and p=0.02, respectively). Among WWH and a history of hot flashes, years since onset of hot flashes related to cardiovascular MRI-derived measures of subclinical pathology. Specifically, years since onset of hot flashes related directly to myocardial steatosis (intramyocardial triglyceride content; ρ=0.80, p=0.02) and inversely to diastolic function (left atrial passive ejection fraction; ρ=─0.70, p=0.03). Conclusions: WWH experienced a higher frequency of hot flashes compared to women without HIV. Among WWH, hot flash symptomatology related to systemic immune activation and to cardiovascular MRI-derived measures of CVD risk. Additional research is required to improve understanding of mechanisms underlying these relationships and determine if hot flashes are a sex-specific risk factor for CVD in WWH.

Immunotherapies, particularly immune checkpoint inhibitors (ICI), are revolutionary cancer therapies being increasingly applied to a broader range of cancers. Our understanding of the mechanism, epidemiology, diagnosis, and treatment of cardiotoxicity related to immunotherapies remains limited. We aim to synthesize the limited current literature on cardiotoxicity of ICIs and to share our opinions on the diagnosis and treatment of this condition. The incidence of ICI-associated myocarditis ranges from 0.1 to 1%. Patients with ICI-associated myocarditis often have a fulminant course with a case fatality rate of 25–50%. The diagnosis of this condition poses many challenges because independently a normal electrocardiogram, biomarkers, or a preserved left ventricular function do not rule out ICI-associated myocarditis. Endomyocardial biopsy should be pursued when clinical suspicion remains despite normal non-invasive tests. Data on optimal screening and surveillance tools are lacking. Cessation of ICIs, combined with high dose corticosteroids and other immunosuppressant approaches are the cornerstones of the treatment of ICI-associated myocarditis. This condition may recur when patients are re-challenged with these agents and the decision to resume ICIs should be made through a multidisciplinary discussion. Immunotherapies have changed the landscape of cancer treatment. Recognizing and managing cardiotoxicity related to ICIs is of critical importance. Our understanding of ICI-cardiotoxicity has improved, but large information gaps remain for further research. Due to the high case fatality rate, any type of cardiac symptoms or signs in a patient who has recently started an ICI should prompt consideration of ICI-cardiotoxicity.

BackgroundAmong persons living with human immunodeficiency virus (PHIV), incident heart failure (HF) rates are increased and outcomes are worse; however, the role of amino-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations among PHIV with HF has not been characterized.MethodsPatients were derived from a registry of those hospitalized with HF at an academic center in a calender year. We compared the NT-proBNP concentrations and the changes in NT-proBNP levels between PHIV with HF and uninfected controls with HF.ResultsAmong 2578 patients with HF, there were 434 PHIV; 90% were prescribed antiretroviral therapy and 62% were virally suppressed. As compared to controls, PHIV had higher admission (3822 [IQR, 2413–7784] pg/ml vs 5546 [IQR, 3257–8792] pg/ml, respectively; P < .001), higher discharge (1922 [IQR, 1045–4652] pg/ml vs 3372 [IQR, 1553–5452] pg/ml, respectively; P < .001), and lower admission-to-discharge changes in NT-proBNP levels (32 vs 48%, respectively; P = .007). Similar findings were noted after stratifying based on left ventricular ejection fraction (LVEF). In a multivariate analysis, cocaine use, a lower LVEF, a higher NYHA class, a higher viral load (VL), and a lower CD4 count were associated with higher NT-proBNP concentrations. In follow-up, among PHIV, a higher admission NT-proBNP concentration was associated with increased cardiovascular mortality (first tertile, 11.5; second tertile, 20; third tertile, 44%; P < .001). Among PHIV, each doubling of NT-proBNP was associated with a 19% increased risk of death. However, among patients living without HIV, each doubling was associated with a 27% increased risk; this difference was attenuated among PHIV with lower VLs and higher CD4 counts.ConclusionsPHIV with HF had higher admission and discharge NT-proBNP levels, and less change in NT-proBNP concentrations. Among PHIV, VLs and CD4 counts were associated with NT-proBNP concentrations; in follow-up, higher NT-proBNP levels among PHIV were associated with cardiovascular mortality.

Objectives This study sought to assess the safety of carvedilol therapy among heart failure (HF) patients with a cocaine-use disorder (CUD). Background Although carvedilol therapy is recommended among certain patients with HF, the safety and efficacy of carvedilol among HF patients with a CUD is unknown. Methods This was a single-center study of hospitalized patients with HF. Cocaine use was self-reported or defined as having a positive urine toxicology. Patients were divided by carvedilol prescription. Subgroup analyses were performed by strata of ejection fraction (EF) ≤40%, 41% to 49%, or ≥50%. Major adverse cardiovascular events (MACE) were defined as cardiovascular mortality and 30-day HF readmission. Results From a cohort of 2,578 patients hospitalized with HF in 2011, 503 patients with a CUD were identified, among whom 404 (80%) were prescribed carvedilol, and 99 (20%) were not. Both groups had similar characteristics; however, those prescribed carvedilol had a lower LVEF, heart rate, and N-terminal pro–B-type natriuretic peptide concentrations at admission and on discharge, and more coronary artery disease. Over a median follow-up of 19 months, there were 169 MACEs. The MACE rates were similar between the carvedilol and the non-carvedilol groups (32% vs. 38%, respectively; p = 0.16) and between those with a preserved EF (30% vs. 33%, respectively; p = 0.48) and were lower in patients with a reduced EF taking carvedilol (34% vs. 58%, respectively; p = 0.02). In a multivariate model, carvedilol therapy was associated with lower MACE among patients with HF with a CUD (hazard ratio: 0.67; 95% confidence interval; 0.481 to 0.863). Conclusions Our findings suggest that carvedilol therapy is safe for patients with HF with a CUD and may be effective among those with a reduced EF.

Human immunodeficiency virus (HIV) imparts increased heart failure risk to women. Among women with HIV (WHIV), immune pathways relating to heart failure precursors may intimate targets for heart failure prevention strategies. Twenty asymptomatic, antiretroviral-treated WHIV and 14 non-HIV-infected women matched on age and body mass index underwent cardiac magnetic resonance imaging and immune phenotyping. WHIV (vs non-HIV-infected women) exhibited increased myocardial fibrosis (extracellular volume fraction, 0.34 ± 0.06 vs 0.29 ± 0.04; P = .002), reduced diastolic function (diastolic strain rate, 1.10 ± 0.23 s(-1) vs 1.39 ± 0.27 s(-1); P = .003), and heightened systemic monocyte activation. Among WHIV, soluble CD163 levels correlated with myocardial fibrosis (r = 0.53; P = .02), while circulating inflammatory CD14(+)CD16(+) monocyte CCR2 expression related directly to myocardial fibrosis (r = 0.48; P = .04) and inversely to diastolic function (r = –0.49; P = .03). Clinical Trials Registration. NCT02874703.

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

As cancer survival has improved, some of the focus of care has shifted to minimizing the long-term complications of cancer therapy. Cardiovascular disease is a leading long-term cause of morbidity and mortality in patients who survive cancer. This chapter focuses on current clinical imaging and non-imaging techniques that are used to detect the cardiovascular consequences of chemotherapy. Overall, the detection and quantification of chemotherapy-induced myocardial injury, dysfunction, and heart failure is challenging due to intrinsic limitations of the available imaging techniques coupled with the latency period that can occur between injury and clinical presentation with heart failure.

Background:Sleep apnea (SA) is common and has prognostic significance among broad groups of patients with heart failure (HF). There are no data characterizing the presence, associations, and prognostic significance of SA among persons living with human immunodeficiency virus (PLHIV) with HF. Methods:We conducted a single-center study of PLHIV with HF with reduced ejection fraction (HFrEF; left ventricular ejection fraction [LVEF]

e18234 Background: Infection with influenza in adults with cancer carries an increased risk of morbidity and mortality. Vaccination against seasonal influenza (Flu-V) can decrease the incidence of influenza, shorten its course, and reduce influenza-associated morbidity. Recent data has suggested that the administration of the Flu-V to patients on an ICI leads to an exaggerated inflammatory response and an increased risk of irAE. However, this trend was demonstrated in a small cohort of patients with lung cancer. Current recommendation for annual Flu-V in patients treated with ICI is unclear and literature about safety is limited. We compared rates of Flu-V for patients on ICI admitted with severe toxicity vs those patients on ICI who were admitted for reasons other than toxicity. We also evaluated rate of Flu-V among oncology patients who had received non-immunotherapy modalities. Methods: We retrospectively evaluated patients treated with ICI who were admitted to Massachusetts General Hospital from February 5, 2011- June 12, 2017. Patients received ipilimumab, pembrolizumab, nivolumab, atezolizumab, durvalumab, avelumab, or a combination in treatment of an advanced solid tumor malignancies including melanoma, NSCLC, SCCHN. Admissions due to irAE were confirmed by review of clinical, radiologic, and pathologic features. Flu-V status was determined by rigorous chart review. Nearest neighbor matching was used to create a control group of cancer patients treated with non-ICI modalities. Descriptive statistics compared rates and timing of Flu-V relative to admission. Statistical significance was determined using Fischer’s Exact Test, p < 0.05. Results: Of 540 patients on ICI, 28% were admitted for irAE, 72% had a non-irAE reason for admission. The rate of Flu-V in the flu season prior to admission for irAE group was lower than for non-irAE (18.5% vs 29.6%; p value = 0.01). There were no differences in vaccination rates within ≤30 days (2.7% vs 3.6%, p = 0.80), ≤90 days (4.0% vs 9.3%, p = 0.05), or ≤180 days of admission (11.9% vs 18.5%, p = 0.07). Flu-V rate overall in patients on ICI was 26.5%. In comparison, Flu-V rate in the nearest neighbor non-immunotherapy oncology patients was 67% (n = 101). Conclusions: Flu-V rates were much lower in patients treated with ICI compared to patients treated with non-ICI modalities. We did not see a higher rate of Flu-V in patients admitted with irAE compared to non-irAE which suggests that Flu-V and severe irAE may not be linked in clinical practice. Additional studies are needed, but Flu-V in patients on ICI holds potential to improve care.

The safety and efficacy of beta-blockers among patients with heart failure (HF) who use cocaine is unknown. Non-cardioselective beta-blockers such as carvedilol may be reasonable among patients with coronary artery disease (CAD) and active cocaine use. We sought to test the safety and effectiveness

Chimeric antigen receptor T-cells (CAR-T) are gene modified and ex-vivoexpanding autologous T cells designed to recognize and attack a specific cell surface antigen; CAR-T has demonstrated significant promise in treating patients with several relapsed or refractory hematologic malignancies. There

Radiation therapy (RT) that involves the cardiac silhouette is associated with a 9-fold increase in incident heart failure (HF) among women with breast cancer (BC). Pathologically, RT-induced cardiotoxicity leads to myocardial fibrosis, atrophy and a reduction in cardiomyocyte mass; cardiac magnetic

Persons with HIV are at an increased risk of heart failure (HF). Ritonavir-based therapy (RBT) is associated with an increase in myocardial fibrosis; however, there are no data testing the effect of RBT on clinical outcomes among patients with HF. We retrospectively analyzed 160 people on ART

127 Background: Disruption of the immune system with immune checkpoint inhibitors can result in a multitude of immune-related adverse effects (irAE). While irAEs have been well-reported in clinical trials, the impact and magnitude of irAE’s in the real-world, particularly inpatient is unclear. Methods: Data was collected on patients with advanced malignancy who experienced a suspected irAE needing admission to an academic hospital (Feb 2011 to June 2017). Each case was reviewed comprehensively by minimum of two reviewers, including one sub-specialist. In addition, oncologists at our institution were surveyed regarding their confidence about managing patients with irAEs. Results: Over a span of 6 years, there were 343 hospitalizations for suspected irAEs and the majority (65%; N = 223) were confirmed irAEs that required treatment with immunosuppression or therapy stopped as result. The mean length of stay was 6.3 days (range 1 to 31 days), readmission rate for another irAE event 25%, total readmission rate 61.7%, and inpatient mortality 8%. The most common irAEs were enterocolitis (43.9%), pulmonary (16%), hepatic (15%), neurological (8.9%), endocrinopathies (7.1%), rheumatological (4%), dermatological (3%), cardiovascular (3%), renal (1.8%), and allergy (1.3%). Over the past 5 years, there was a significant increase in admissions due to irAEs (admissions in 2016 vs 2011, odds ratio = 3.07; p < 0.01). The Cancer Center survey (N = 26) revealed majority of oncologists do not feel very comfortable managing irAEs, and 48% felt that irAE complications should be managed on a different service. Conclusions: irAEs from immune checkpoint inhibitors can result in prolonged hospitalizations, high rate of readmissions, and mortality. The number of patients admitted due to irAEs has significantly increased by more than three-fold in the recent years, but majority of oncologists do not feel very comfortable managing irAEs. Consequently, there is a critical need for coordinated multidisciplinary approach, comprehensive provider education, and translational research program for early detection and intervention.

Table S1. (3-month cut-off): Comparison of Myocarditis cases withâ Ą and without Flu vaccination (FV). (DOCX 22 kb)

Table S1. (3-month cut-off): Comparison of Myocarditis cases withâ Ą and without Flu vaccination (FV). (DOCX 22 kb)