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Effect of transcatheter edge-to-edge repair (TEER) using MitraClip in patients with mitral regurgitation (MR) on left atrial (LA) kinetic energy (LAKE), an index of LA work, and LA strain, a measure of LA performance, have not been well defined.Patients with chronic primary or secondary 3+ or 4+ MR were analyzed pre- and post-TEER using MitraClip. LAKE was determined by echocardiography using LA stroke volume and A-wave velocity. Peak atrial longitudinal strain (PALS), peak atrial strain in early diastole, and peak atrial contraction strain (PACS) were obtained by speckle tracking echocardiography.Thirty-nine patients undergoing TEER with MitraClip were screened, 12 met criteria for analysis (9 primary and 3 secondary MR). Compared to pre-TEER, there was a significant increase post-TEER in LAKE (71.0 ± 64.1 vs. 177.5 ± 167.9 dyne·cm·10sup3/sup, respectively; p = .008) and Doppler transmitral A-wave velocity (87.8 ± 41.4 vs. 138.5 ± 43.7 cm/s, respectively; p lt; .001); LA stroke volume did not change significantly. Mitral valve mean gradient significantly increased post-TEER compared to pre-TEER (5.7 ± 2.1 vs. 3.3 ± 2.1 mmHg, respectively; p = .01). There was a trend toward decrease in PALS post-TEER compared to pre-TEER (16.2 ± 4.8 vs. 20.7 ± 9.9%, respectively; p = .05). Peak atrial strain in early diastole significantly decreased post-TEER compared to pre-TEER (7.2 ± 3.0 vs. 14.1 ± 7.2%; respectively, p lt; .001), while PACS did not significantly change (9.1 ± 3.5 vs. 6.7 ± 5.2%, respectively; p = .07).In patients with chronic MR, LAKE increases after TEER with MitraClip driven by an increase in LA emptying velocities. Changes were also seen in LA strain with MitraClip. These procedurally induced changes due to mild mitral stenosis may have clinical implications.

In patients with transcatheter aortic valve implantation (TAVI), accurate assessment of gradients is important to assess valve function and durability, which drives clinical decision-making. We sought to evaluate discrepancies in aortic valve mean gradients with balloon-expandable and self-expanding TAVI.We retrospectively reviewed 507 patients that underwent TAVI and compared mean gradients by catheterization to transthoracic Doppler echocardiography.Mean gradients by Doppler in balloon-expandable (11.0 ± 5.8 mm Hg) and self-expanding devices (8.7 ± 4.5 mm Hg) were significantly higher than catheterization (3.2 ± 4.0 mm Hg vs 3.5 ± 4.1 mm Hg, respectively; P.001). In a subgroup analysis of skirted valves, Doppler gradients in balloon-expandable (9.8 ± 4.4 mm Hg) and self-expanding devices (8.6 ± 5.1 mm Hg) were significantly higher than catheterization (3.5 ± 4.1 mm Hg vs 4.2 ± 4.8 mm Hg, respectively; P.001). When the effect of valve size on gradients was analyzed, Doppler gradients were significantly higher than catheterization for all comparisons. When indexed for valve size, patients with large aortas who received a balloon-expandable TAVI had greater pressure differential than those who received a self-expanding TAVI (8.24 ± 0.46 mm Hg vs 5.16 ± 0.66 mm Hg; P.001). This trend was not seen in patients with a small aorta-to-valve index.Following TAVI, aortic valve mean gradients acquired by Doppler were higher than catheterization and the discrepancy was more pronounced in balloon-expandable than self-expanding prostheses. These differences persist in skirted valves and across valve sizes. These observations may reflect periprocedural hemodynamic changes, differences between prosthetic flow acceleration, and/or pressure recovery.

The objective of this study was to determine whether survival and post-arrest procedural utilization following in-hospital cardiac arrest (IHCA) differ in patients with and without comorbid cancer.We retrospectively reviewed all adult (age ≥18 years old) hospital admissions complicated by IHCA from 2003 to 2014 using the National Inpatient Sample (NIS) dataset. Utilizing propensity score matching using age, gender, race, insurance, all hospital level variables, HCUP mortality score, diabetes, hypertension and cardiopulmonary resuscitation use, rates of survival to hospital discharge and post-arrest procedural utilization were compared.From 2003 to 2014, there were a total of 1,893,768 hospitalizations complicated by IHCA, of which 112,926 occurred in patients with history of cancer. In a propensity matched cohort from 2012 to 2014, those with cancer were less likely to survive the hospitalization (31% vs. 46%, p 0.0001). Following an IHCA, rates of procedural utilization in patients with cancer were significantly less when compared to those without a concurrent malignancy: coronary angiography (4.0% vs. 13.0%), percutaneous coronary intervention (2.2% and 8.0%), targeted temperature management (0.8% vs. 6.0%); p 0.0001 for all comparisons. This patient population was less likely to have acute coronary syndrome (12.6% vs. 27.0%) or congestive heart failure (24.5% vs. 38.2%); p 0.0001 for both comparisons. Survival improved in both groups over the study period (p 0.0001).Patients with a history of cancer who sustain IHCA are less likely to receive post-arrest procedures and survive to hospital discharge. Given the expected rise in the rates of cancer survivorship, these findings highlight the need for broader application of potentially life-saving interventions to lower risk cancer patients who have sustained a cardiac arrest.

BackgroundChimeric antigen receptor T-cell (CAR-T) infusion is associated with early toxicity. Yet, whether early toxicity development holds ramifications for long-term outcomes is unknown.MethodsFrom a large cohort of consecutive adult patients treated with CAR-T therapies for relapsed or refractory lymphomas from 2016 to 2019, we assessed progression-free survival (PFS), by toxicity development (cytokine release syndrome (CRS), neurotoxicity, or cardiotoxicity]. We also assessed the relationship of toxicity development to objective disease response, and overall survival (OS). Multivariable regression was utilized to evaluate relationships between standard clinical and laboratory measures and disease outcomes. Differences in outcomes, by toxicity status, were also assessed via 30-day landmark analysis. Furthermore, we assessed the effects of early anti-CRS toxicity therapy use (at ≤grade 2 toxicity) on maximum toxicity grade observed, and long-term disease outcomes (PFS and OS).ResultsOverall, from 102 CAR-T-treated patients, 90 were identified as treated with single-agent therapy, of which 88.9% developed toxicity (80 CRS, 41 neurotoxicity, and 17 cardiotoxicity), including 28.9% with high-grade (≥3) events. The most common manifestations were hypotension at 96.6% and fever at 94.8%. Among patients with cardiac events, there was a non-significant trend toward a higher prevalence of concurrent or preceding high-grade (≥3) CRS. 50.0% required tocilizumab or corticosteroids. The median time to toxicity was 3 days; high grade CRS development was associated with cardiac and neurotoxicity. In multivariable regression, accounting for disease severity and traditional predictors of disease response, moderate (maximum grade 2) CRS development was associated with higher complete response at 1 year (HR: 2.34; p=0.07), and longer PFS (HR: 0.41; p=0.02, in landmark analysis), and OS (HR: 0.43; p=0.03). Among those with CRS, relative blood pressure (HR: 2.25; p=0.004), respectively, also associated with improved PFS. There was no difference in disease outcomes, or maximum toxicity grade (CRS, neurotoxicity, or cardiotoxicity) observed, based on the presence or absence of the use of early CRS-directed therapies.ConclusionsAmong adult lymphoma patients, moderate toxicity manifest as grade 2 CRS after CAR-T infusion may associate with favorable clinical outcomes. Further studies are needed to confirm these findings.

A 68-year-old male with a witnessed out-of-hospital cardiac arrest while jogging who was managed with extracorporeal cardiopulmonary resuscitation (ECPR) is presented. The patient was found to be in refractory ventricular fibrillation by emergency medical service personnel and underwent advanced cardiac life support (ACLS) protocol with placement of an automated chest compression device. He was emergently transported to the cardiac catheterization laboratory. Due to refractory ventricular fibrillation, he was placed on venoarterial extracorporeal membranous oxygenation (VA-ECMO). Coronary angiography at that time showed nonobstructive coronary artery disease. Management with VA-ECMO and other supportive measures were continued for 5 days, after which a cardiac magnetic resonance imaging was performed with findings consistent with acute myocarditis. His condition substantially improved, and he was discharged from the hospital with good neurologic and functional status. Fulminant myocarditis is often fatal, but aggressive supportive measures with novel ECPR protocols may result in recovery, as it happened in this case.

Activin type II receptor (ActRII) ligands have been implicated in muscle wasting in aging and disease. However, the role of these ligands and ActRII signaling in the heart remains unclear. Here, we investigated this catabolic pathway in human aging and heart failure (HF) using circulating follistatin-like 3 (FSTL3) as a potential indicator of systemic ActRII activity. FSTL3 is a downstream regulator of ActRII signaling, whose expression is up-regulated by the major ActRII ligands, activin A, circulating growth differentiation factor-8 (GDF8), and GDF11. In humans, we found that circulating FSTL3 increased with aging, frailty, and HF severity, correlating with an increase in circulating activins. In mice, increasing circulating activin A increased cardiac ActRII signaling and FSTL3 expression, as well as impaired cardiac function. Conversely, ActRII blockade with either clinical-stage inhibitors or genetic ablation reduced cardiac ActRII signaling while restoring or preserving cardiac function in multiple models of HF induced by aging, sarcomere mutation, or pressure overload. Using unbiased RNA sequencing, we show that activin A, GDF8, and GDF11 all induce a similar pathologic profile associated with up-regulation of the proteasome pathway in mammalian cardiomyocytes. The E3 ubiquitin ligase, Smurf1, was identified as a key downstream effector of activin-mediated ActRII signaling, which increased proteasome-dependent degradation of sarcoplasmic reticulum Ca(2+) ATPase (SERCA2a), a critical determinant of cardiomyocyte function. Together, our findings suggest that increased activin/ActRII signaling links aging and HF pathobiology and that targeted inhibition of this catabolic pathway holds promise as a therapeutic strategy for multiple forms of HF.

Introduction CART-cell therapy is associated with dramatic efficacy in patients with relapsed/refractory diffuse large B-cell lymphoma and B-acute lymphoblastic leukemia. However, the efficacy of CART therapy is limited by potentially fatal toxicities including cytokine release syndrome (CRS) and neurotoxicity. Increasingly, emerging reports have suggested the potential for significant hemodynamic collapse following CART therapy. Yet, whether the occurrence of these hemodynamic shifts or any other cardiovascular disease (CVD) events have bearing on clinical outcomes after CART initiation is unknown. Methods We evaluated all patients treated with CART therapy for lymphoid malignancies at The Ohio State University James Comprehensive Cancer Center between 2016-2019 and assessed the incidence of CVD events and severe hemodynamic collapse [systolic blood pressure (SBP) cutoff of less than 80 mmHg]. We also evaluated the relationship of CVD events, hemodynamic collapse, and the presence of preceding CVD on overall survival (OS) and progression-free-survival (PFS) following infusion of CART cells utilizing univariate log-rank comparison. Results We evaluated 66 patients with 62% male and 38% female with an average age of 60 years (range 23-80). 49 (74%) patients received Yescarta and 17 (26%) patients received Kymriah. With a median follow-up time of 21 months, OS and PFS at 1 year were 72% and 43%, respectively, in concordance with previously reported ZUMA1 and JULIET survival rates. Overall, from 66 CART-treated patients, 14 (21.2%) developed incident CVD events, including 11 patients with arrhythmias and 2 with CHF. The median decrease in peak systolic blood pressure after infusion was 32 mmHg (IQR 22-47 mmHg), noted at a median of 4 days post-CART. Furthermore, after infusion, 17 (25.8%) saw falls in systolic pressure to Conclusion The development of significant early hypotension is associated with a marked decrease in survival among patients receiving CART therapy. Further understanding of this finding, and its relation to CRS is urgently needed in order to maximize the effectiveness of this novel anticancer therapy.