JACC: Standardizing definitions takes hold in TAVR studies

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Comparing results from clinical trials often is hampered by inconsistencies in methodology and definitions. The Valve Academic Research Consortium (VARC) attempted to cut that problem off at the pass by publishing standardized definitions for transcatheter aortic valve replacement (TAVR) studies. VARC definitions have caught on among researchers, according to a meta-analysis whose findings may add clarity to previously reported outcomes.

The study appeared in the June 19/26 issue of the Journal of the American College of Cardiology.

Martin B. Leon, MD, of Columbia University Medical Center, New York-Presbyterian Hospital in New York City, and colleagues designed the study to evaluate the use and performance of VARC definitions in TAVR literature. They searched in PubMed, Cochrane and EMBASE databases for relevant published studies that reported outcomes with at least one VARC definition between Jan. 1, 2001, and Oct. 12, 2011. Their final pool included 16 studies with 3,519 patients who received implanted devices.

They determined minimum and maximum outcome rates as well as cumulative rates for each VARC outcome. The pooled estimate rate for overall device success was 92.1 percent; for severe aortic regurgitation, 7.4 percent; for aortic valve area (AVA) of less than 1.2 cm2, 4.8 percent; for failure of delivery or implantation of the device in the correct position, 3.5 percent.

They also calculated 30-day mortality rates, for a pooled estimate of 7.8 percent, with cardiovascular death accounting for most of that mortality. Under complications, MI had a pooled estimate of 1.1 percent and acute kidney injury of 20.4 percent. Life-threatening bleeding and major vascular complications had pooled estimated rates of 15.6 percent and 11.9 percent, respectively; the estimated rate for stroke and transient ischemic attacks was 5.7 percent. The pooled rate for new permanent pacemaker implantation after TAVR was 13.9 percent.

The authors wrote that their analysis showed that VARC definitions are being widely used and have brought uniformity to TAVR research. “The pooled estimate outcomes after TAVR reported in this meta-analysis represent a new standard of quality for TAVR clinical research,” they claimed, adding that they identified issues with initial VARC definitions and opportunities for refinements and modifications.     

“The device success rate of the current pooled analysis appears to be lower than previously reported,” Leon and colleagues noted. “This difference is mostly explained by the fact that VARC uses stricter definitions, with echocardiography-derived criteria not used before, such as AVA of less than 1.2 cm2 and residual moderate to severe prosthetic valve aortic regurgitation.”

They observed that the meta-analysis 30-day mortality rate was similar to early registry reports, with cardiovascular mortality making up more than 65 percent of total mortality in their study. Attributing unknown death to cardiovascular death has been questioned, they wrote, and by current VARC definitions, unknown deaths are considered cardiovascular in origin. “Although VARC suggests the use of all-cause mortality as the primary endpoint of choice and cardiovascular mortality as a secondary endpoint, ascertainment and adjudication of cardiovascular death remain a challenge,” they acknowledged.

They pointed out that post-TAVR life-threatening and major bleeding rates were higher in the pooled estimate compared with previous reports. They attributed that to inconsistent reporting and under-reporting. They added that VARC also recommends reporting rates of transfusions after TAVR.

Stroke rates also have been variably reported. “These were mostly self- or site-reported results and nonadjudicated events,” they wrote. “VARC emphasizes the necessity to confirm the diagnosis by neuroimaging technique (computed tomography and/or magnetic resonance imaging) and to classify the severity of stroke using conventional neurological assessment tools.”

The authors said they would have preferred a patient-level analysis to the study-level analysis used for this study, and noted that 14 of the 16 studies were primarily self-reported or site-reported, leading to high heterogeneity. Nonetheless, the meta-analysis showed that the definitions are being used in the literature and are being adopted by the research community.   

“Although VARC definitions have brought uniformity and standardization in reporting outcomes after TAVR, appropriate recognition and ascertaining, reporting and adjudication of outcomes should be reinforced and will ensure that TAVR study results are a valid reflection of ‘real-world’ clinical events,” Leon and colleagues concluded.