Research Spotlight

Lindenfeld, J., Abraham, W.T., Grayburn, P.A., Kar, S., Asch, F.M., Lim, D.S., Nie, H., Singhal, P., Sundareswaran, K.S., Weissman, N.J., Mack, M.J. and Stone, G.W. (2021). “Association of Effective Regurgitation Orifice Area to Left Ventricular End-Diastolic Volume Ratio With Transcatheter Mitral Valve Repair Outcomes: A Secondary Analysis of the COAPT Trial.” JAMA Cardiol Feb 3;e207200. [ Epub ahead of print].

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IMPORTANCE: Transcatheter mitral valve repair (TMVr) plus maximally tolerated guideline-directed medical therapy (GDMT) reduced heart failure (HF) hospitalizations (HFHs) and all-cause mortality (ACM) in symptomatic patients with HF and secondary mitral regurgitation (SMR) compared with GDMT alone in the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation (COAPT) trial but not in a similar trial, Multicenter Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients With Severe Secondary Mitral Regurgitation (MITRA-FR), possibly because the degree of SMR relative to the left ventricular end-diastolic volume index (LVEDVi) was substantially lower. OBJECTIVE: To explore contributions of the degree of SMR using the effective regurgitation orifice area (EROA), regurgitant volume (RV), and LVEDVi to the benefit of TMVr in the COAPT trial. DESIGN, SETTING, AND PARTICIPANTS: This post hoc secondary analysis of the COAPT randomized clinical trial performed December 27, 2012, to June 23, 2017, evaluated a subgroup of COAPT patients (group 1) with characteristics consistent with patients enrolled in MITRA-FR (n = 56) (HF with grade 3+ to 4+ SMR, left ventricular ejection fraction of 20%-50%, and New York Heart Association function class II-IV) compared with remaining (group 2) COAPT patients (n = 492) using the end point of ACM or HFH at 24 months, components of the primary end point, and quality of life (QOL) (per the Kansas City Cardiomyopathy Questionnaire overall summary score) and 6-minute walk distance (6MWD). The same end points were evaluated in 6 subgroups of COAPT by combinations of EROA and LVEDVi and of RV relative to LVEDVi. INTERVENTIONS: Interventions were TMVr plus GDMT vs GDMT alone. RESULTS: A total of 548 participants (mean [SD] age, 71.9 [11.2] years; 351 [64%] male) were included. In group 1, no significant difference was found in the composite rate of ACM or HFH between TMVr plus GDMT vs GDMT alone at 24 months (27.8% vs 33.1%, P = .83) compared with a significant difference at 24 months (31.5% vs 50.2%, P < .001) in group 2. However, patients randomized to receive TMVr vs those treated with GDMT alone had significantly greater improvement in QOL at 12 months (mean [SD] Kansas City Cardiomyopathy Questionnaire summary scores: group 1: 18.36 [5.38] vs 0.43 [4.00] points; P = .01; group 2: 16.54 [1.57] vs 5.78 [1.82] points; P < .001). Group 1 TMVr-randomized patients vs those treated with GDMT alone also had significantly greater improvement in 6MWD at 12 months (mean [SD] paired improvement: 39.0 [28.6] vs -48.0 [18.6] m; P = .02). Group 2 TMVr-randomized patients vs those treated with GDMT alone tended to have greater improvement in 6MWD at 12 months, but the difference did not reach statistical significance (mean [SD] paired improvement: 35.0 [7.7] vs 16.0 [9.1] m; P = .11). CONCLUSIONS AND RELEVANCE: A small subgroup of COAPT-resembling patients enrolled in MITRA-FR did not achieve improvement in ACM or HFH at 24 months but had a significant benefit on patient-centered outcomes (eg, QOL and 6MWD). Further subgroup analyses with 24-month follow-up suggest that the benefit of TMVr is not fully supported by the proportionate-disproportionate hypothesis. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01626079.

Grayburn, P.A. and Thomas, J.D. (2021). “Basic Principles of the Echocardiographic Evaluation of Mitral Regurgitation.” JACC Cardiovasc Imaging Jan 13;S1936-878X(20)31101-3. [Epub ahead of print].

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Mitral regurgitation (MR) is a common form of valvular heart disease that is associated with significant morbidity and mortality. Treatment decisions are completely dependent on accurate diagnosis of both mechanism and severity of MR, which can be challenging and is often done incorrectly. Transthoracic echocardiography is the most commonly used imaging test for MR; transesophageal echocardiography is often needed to better define morphology and MR severity, and is essential for guiding transcatheter therapies for MR. Multidetector computed tomography has become the standard to assess whether transcatheter valve replacement is an option because of its ability to assess valve sizing, access, and potential left ventricular outflow tract obstruction. Finally, cine cardiac magnetic resonance has been recommended by recent guidelines to quantify MR severity when the distinction between moderate and severe MR is indeterminate by echocardiography. This paper focuses on the main questions to be answered by imaging techniques and illustrates some common tips, tricks, and pitfalls in the assessment of MR.

Davidson, C.J., Lim, D.S., Smith, R.L., Kodali, S.K., Kipperman, R.M., Eleid, M.F., Reisman, M., Whisenant, B., Puthumana, J., Abramson, S., Fowler, D., Grayburn, P., Hahn, R.T., Koulogiannis, K., Pislaru, S.V., Zwink, T., Minder, M., Dahou, A., Deo, S.H., Vandrangi, P., Deuschl, F., Feldman, T.E. and Gray, W.A. (2021). “Early Feasibility Study of Cardioband Tricuspid System for Functional Tricuspid Regurgitation: 30-Day Outcomes.” JACC Cardiovasc Interv 14(1): 41-50.

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OBJECTIVES: The study reports for the first time the 30-day outcomes of the first U.S. study with the Cardioband tricuspid valve reconstruction system for the treatment of functional tricuspid regurgitation (TR). BACKGROUND: Increasing severity of TR is associated with progressively higher morbidity and mortality; however, treatment options for isolated significant disease are limited. METHODS: In this single-arm, multicenter, prospective Food and Drug Administration-approved early feasibility study (EFS), 30 patients with severe or greater symptomatic functional TR were enrolled who were deemed candidates for transcatheter tricuspid repair with the Cardioband tricuspid system by the local heart team and multidisciplinary screening committee. RESULTS: The mean patient age was 77 years, 80% were women, 97% had atrial fibrillation, 70% were in New York Heart Association functional class III to IV with mean left ventricular ejection fraction of 58%, and 27% had severe, 20% massive, and 53% torrential TR. Device success was 93% and all patients were alive at 30 days. Between baseline and 30 days, septolateral tricuspid annular diameter was reduced by 13% (p < 0.001), 85% of patients had ≥1 grade TR reduction and 44% had ≤moderate TR, 75% were in New York Heart Association functional class I to II (p < 0.001), and overall Kansas City Cardiomyopathy Questionnaire score improved by 16 points (p < 0.001). CONCLUSIONS: In patients with severe symptomatic functional TR, this is the first study in the United States with the Cardioband tricuspid system for direct transcatheter annular reduction. This early feasibility study demonstrates high procedural feasibility with no 30-day mortality. There is significant reduction of functional TR with clinically significant improvements in functional status and quality of life. (Edwards Cardioband Tricuspid Valve Reconstruction System Early Feasibility Study; NCT03382457).

van Zyl, J.S., Alam, A., Felius, J., Youssef, R.M., Bhakta, D., Jack, C., Jamil, A.K., Hall, S.A., Klintmalm, G.B., Spak, C.W. and Gottlieb, R.L. (2021). “ALLY in fighting COVID-19: magnitude of albumin decline and lymphopenia (ALLY) predict progression to critical disease.” J Investig Med Jan 11;jim-2020-001525. [Epub ahead of print].

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The global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic leading to coronavirus disease 2019 (COVID-19) is straining hospitals. Judicious resource allocation is paramount but difficult due to the unpredictable disease course. Once hospitalized, discerning which patients may progress to critical disease would be valuable for resource planning. Medical records were reviewed for consecutive hospitalized patients with COVID-19 in a large healthcare system in Texas. The main outcome was progression to critical disease within 10 days from admission. Albumin trends from admission to 7 days were analyzed using mixed-effects models, and progression to critical disease was modeled by multivariable logistic regression of laboratory results. Risk models were evaluated in an independent group. Of 153 non-critical patients, 28 (18%) progressed to critical disease. The rate of decrease in mean baseline-corrected (Δ) albumin was -0.08 g/dL/day (95% CI -0.11 to -0.04; p<0.001) or four times faster, in those who progressed compared with those who did not progress. A model of Δ albumin combined with lymphocyte percentage predicting progression to critical disease was validated in 60 separate patients (sensitivity, 0.70; specificity, 0.74). ALLY (delta albumin and lymphocyte percentage) is a simple tool to identify patients with COVID-19 at higher risk of disease progression when: (1) a 0.9 g/dL or greater albumin drop from baseline within 5 days of admission or (2) baseline lymphocyte of ≤10% is observed. The ALLY tool identified >70% of hospitalized cases that progressed to critical COVID-19 disease. We recommend prospectively tracking albumin. This is a globally applicable tool for all healthcare systems.

Gottlieb, R.L. and Spak, C.W. (2021). “The Olympiad of SARS-CoV-2 vaccinology: Fundamentals to Complement Technical Frontiers.” Clin Infect Dis Jan 30;ciab088. [Epub ahead of print].

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SARS-CoV-2 is a consequential and devastating virus, yet it is unlikely to be a particularly “fit,” having limited genomic size and a constrained sequence space to sample for escape mutations. If spike mutations happen to decrease efficacy of spike-specific vaccine strategies, the world may require comparative efficacy data from multiple workarounds. Chimeric derivatives of mRNA or vectored vaccines encoding various different spike variant cassettes may suffice, but inactivated vaccines offer a back-up of alternative epitopes just in case. Like saline for cholera, or like a goal in sports, vaccinology does not need to be fancy… it just needs to work. The world eagerly awaits the next steps – objective data from phase 3 trials of this, and similar, inactivated SARS-CoV-2 vaccines. [No abstract; excerpt from article].