Atrial fibrillation, left ventricular ejection fraction (LVEF), abnormal right ventricular function, and ventricular hypertrophy were found to be associated with a greater risk for aortic valve replacement (AVR), death, or hospitalization for heart failure in patients with moderate aortic stenosis, according to a study published in The American Journal of Cardiology.

In this retrospective single-center study, 151 patients (age ≥18 years; index echocardiogram between 2014 and 2017) with moderate aortic stenosis were enrolled. Aortic stenosis was defined as maximum transvalvular velocity between 3.0 and 4.0 m/s, dimensionless index between 0.25 and 0.50, mean transvalvular pressure gradient between 20 and 40 mmHg, and valve area between 1.0 to 1.5 cm2. Composite end points were hospitalization for heart failure, AVR, or all-cause death. The time to event for each end point was analyzed using Kaplan-Meier analysis, and independent risk factors for each composite end point were identified using multivariable Cox proportional hazards. 

The most common end point was transcatheter aortic valve implantation or surgical AVR, which occurred in 51% of participants (n=77), hospitalization for heart failure, which occurred in 20% of patients (n=30), and all-cause death (9%; n=13).


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The composite outcomes of AVR or hospitalization for heart failure and the composite of hospitalization for heart failure, AVR, or all-cause death, which occurred in 61% and 66% of participants, respectively (n=93 and n=99, respectively), were found to be associated with reduced ejection fraction (hazard ratio [HR], 4.1; 95% CI, 2.3-7.1; P <.001, and HR, 3.8; 95% CI, 2.2-6.6; P <.001, respectively), reduced aortic valve area (HR, 0.3; 95% CI, 0.1-0.6; P =.003, and HR, 0.25; 95% CI, 0.1-0.6; P =.001, respectively), atrial fibrillation (HR, 2.0; 95% CI, 1.2-3.2; P =.006, and HR, 2.1; 95% CI, 1.4-3.2; P =.001, respectively), abnormal right ventricular function (HR, 5.5; 95% CI, 3.0-9.8; P <.001, and HR, 4.3; 95% CI, 2.5-7.5; P <.001, respectively), and higher aortic valve mean gradient (HR, 1.06; 95% CI, 1.03-1.09; P <.001, and HR, 1.05; 95% CI, 1.02-1.08; P =.001). 


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Study limitations include its retrospective design, a lack of accounting for the variable durations of moderate aortic stenosis prior to the first echocardiogram, and the reliance on echocardiographic assessments for the classification of aortic stenosis.  “[O]ur study identified LVEF, atrial fibrillation, left ventricular hypertrophy, and abnormal [right ventricular] function as associated with [heart failure] hospitalization, AVR or death in patients with ]moderate aortic stenosis],” noted the study authors.

Reference

Murphy KR, Khan OA, Rassa AC, et al. Clinical and echocardiographic predictors of outcomes in patients with moderate (mean transvalvular gradient 20 to 40 mmHg) aortic stenosis [published online October 2, 2019]. Am J Cardiol. doi: j.amjcard.2019.09.022

Survivors of thrombotic thrombocytopenic purpura (TTP) appear to have a 2-fold greater mortality rate compared with the general US population when adjusted for age, sex, and race, according to study findings presented by Senthil Sukumar, MD, of The Ohio State University in Columbus, Ohio at the virtual 62nd American Society of Hematology (ASH) Annual Meeting and Exposition.

“TTP survivors were initially thought to return to their baseline levels of health after the acute events; however, long-term follow up has shown us that these patients exhibit high rates of adverse health sequelae,” said Dr Sukumar.

To further understand the effects of these continued health consequences on survivors of TTP, Dr Sukumar and colleagues conducted a multicenter cohort study evaluating long-term mortality and causes of death in patients who survived a first TTP episode.

The investigators reviewed all available patient data in The Ohio State University and Johns Hopkins Hospital Thrombotic Microangiopathy (TMA) registries and identified patients with confirmed TTP based on ADAMTS13 activity (<10% during an acute episode). Primary and secondary causes of death were evaluated, and data on patient demographics, details of TTP history, and comorbidities were collected to evaluate risk factors for reduced survival.

Overall, 222 patients who were enrolled in the registries from 2003 to 2020 were included in the analysis. Most of the patients were women (70.3%), and the median age at enrollment was 42 years (interquartile range [IQR], 29-55). During follow-up of 4 years (IQR, 0-11), 38 patients died: 9 (23.6%) did not survive a first TTP episode, and 29 (76.3%) died after surviving a first TTP episode.

Significant differences between patients who died or survived a first TTP episode were seen in total number of TTP episodes (1 vs 3; P <.001), proportion with chronic kidney disease (19.0% vs 48.3%; P =.001), and median average remission ADAMTS13 activity (63.2% vs 39.0%; P =.010).

Compared with the general US population, the median age at death for patients who survived a first TTP episode was lower (49 years for TTP vs 78.7 years for the general population). The mortality rate in survivors of TTP was significantly higher than the expected mortality rate for the reference US population regardless of race or sex (2228.3 per 100,000 person years vs 1273.8 per 100,000 person years, P =.007).

The leading causes of death in survivors of TTP included TTP relapse (27.6%) and cardiovascular disease (27.6%), followed by cancer (20.7%), infectious causes (13.8%), and other unknown causes of death (10.3%).

Significant risk factors for mortality in survivors of TTP identified in a multivariate analysis adjusted for hypertension, chronic kidney disease, and systemic lupus erythematosus were male sex (hazard ratio [HR], 4.39; 95% CI, 1.83-10.52; P =.001), age (HR, 1.03; 95% CI, 1.01-1.06; P =.039), and number of TTP episodes (HR, 1.12; 95% CI, 1.05-1.21; P =.001).

Given these results, the investigators highlight the need to screen for and actively manage cardiovascular risk factors in survivors of TTP.

“[O]ur data suggests that TTP survivors have a 2-fold higher mortality than expected based on the US reference population,” concluded Dr Sukumar. “Reduced ADAMTS13 activity in remission is a possible targetable risk factor for early death, though the underlying mechanism is not clearly understood.”

Future prospective studies are needed to examine the vascular sequelae of TTP.

Disclosure: Some authors have declared affiliations with or received funding from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.

Read more of Hematology Advisor’s coverage of the ASH 2020 meeting by visiting the conference page.

Reference

Sukumar S, Brodsky M, Hussain S, Cataland S, Chaturvedi S. Cardiovascular disease is a leading cause of death in thrombotic thrombocytopenic purpura (TTP) survivors. Presented at: American Society of Hematology (ASH) 62nd Annual Meeting and Exposition; December 5-8, 2020. Abstract 377. 

This article originally appeared on Hematology Advisor