Research Spotlight

Posted July 15th 2021

Prevention and Attenuation of Covid-19 with the BNT162b2 and mRNA-1273 Vaccines.

Manjusha Gaglani M.D.

Manjusha Gaglani M.D.

Thompson, M.G., Burgess, J.L., Naleway, A.L., Tyner, H., Yoon, S.K., Meece, J., Olsho, L.E.W., Caban-Martinez, A.J., Fowlkes, A.L., Lutrick, K., Groom, H.C., Dunnigan, K., Odean, M.J., Hegmann, K., Stefanski, E., Edwards, L.J., Schaefer-Solle, N., Grant, L., Ellingson, K., Kuntz, J.L., Zunie, T., Thiese, M.S., Ivacic, L., Wesley, M.G., Mayo Lamberte, J., Sun, X., Smith, M.E., Phillips, A.L., Groover, K.D., Yoo, Y.M., Gerald, J., Brown, R.T., Herring, M.K., Joseph, G., Beitel, S., Morrill, T.C., Mak, J., Rivers, P., Poe, B.P., Lynch, B., Zhou, Y., Zhang, J., Kelleher, A., Li, Y., Dickerson, M., Hanson, E., Guenther, K., Tong, S., Bateman, A., Reisdorf, E., Barnes, J., Azziz-Baumgartner, E., Hunt, D.R., Arvay, M.L., Kutty, P., Fry, A.M. and Gaglani, M. (2021). “Prevention and Attenuation of Covid-19 with the BNT162b2 and mRNA-1273 Vaccines.” N Engl J Med Jun 30. [Epub ahead of print].

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BACKGROUND: Information is limited regarding the effectiveness of the two-dose messenger RNA (mRNA) vaccines BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) in preventing infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and in attenuating coronavirus disease 2019 (Covid-19) when administered in real-world conditions. METHODS: We conducted a prospective cohort study involving 3975 health care personnel, first responders, and other essential and frontline workers. From December 14, 2020, to April 10, 2021, the participants completed weekly SARS-CoV-2 testing by providing mid-turbinate nasal swabs for qualitative and quantitative reverse-transcriptase-polymerase-chain-reaction (RT-PCR) analysis. The formula for calculating vaccine effectiveness was 100% × (1 - hazard ratio for SARS-CoV-2 infection in vaccinated vs. unvaccinated participants), with adjustments for the propensity to be vaccinated, study site, occupation, and local viral circulation. RESULTS: SARS-CoV-2 was detected in 204 participants (5%), of whom 5 were fully vaccinated (≥14 days after dose 2), 11 partially vaccinated (≥14 days after dose 1 and <14 days after dose 2), and 156 unvaccinated; the 32 participants with indeterminate vaccination status (<14 days after dose 1) were excluded. Adjusted vaccine effectiveness was 91% (95% confidence interval [CI], 76 to 97) with full vaccination and 81% (95% CI, 64 to 90) with partial vaccination. Among participants with SARS-CoV-2 infection, the mean viral RNA load was 40% lower (95% CI, 16 to 57) in partially or fully vaccinated participants than in unvaccinated participants. In addition, the risk of febrile symptoms was 58% lower (relative risk, 0.42; 95% CI, 0.18 to 0.98) and the duration of illness was shorter, with 2.3 fewer days spent sick in bed (95% CI, 0.8 to 3.7). CONCLUSIONS: Authorized mRNA vaccines were highly effective among working-age adults in preventing SARS-CoV-2 infection when administered in real-world conditions, and the vaccines attenuated the viral RNA load, risk of febrile symptoms, and duration of illness among those who had breakthrough infection despite vaccination. (Funded by the National Center for Immunization and Respiratory Diseases and the Centers for Disease Control and Prevention.).


Posted July 15th 2021

Impact of Predilation During Transcatheter Aortic Valve Replacement: Insights From the PARTNER 3 Trial.

Michael J. Mack M.D.

Michael J. Mack M.D.

Ternacle, J., Al-Azizi, K., Szerlip, M., Potluri, S., Hamandi, M., Blanke, P., Leipsic, J., Dahou, A., Salaun, E., Vincent, F., Rogers, E., Alu, M.C., Lu, M., Yu, X., Thourani, V.H., Hahn, R.T., Leon, M.B., Pibarot, P. and Mack, M.J. (2021). “Impact of Predilation During Transcatheter Aortic Valve Replacement: Insights From the PARTNER 3 Trial.” Circ Cardiovasc Interv Jun 18;CIRCINTERVENTIONS120010336. [Epub ahead of print]. Circinterventions120010336.

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BACKGROUND: The use of predilation during transcatheter aortic valve replacement (TAVR) is variable, and its association with outcomes remains unknown. We evaluated the impact of predilation versus no predilation (direct TAVR) in the low-risk population enrolled in the PARTNER 3 trial (Placement of Aortic Transcatheter Valves). METHODS: In the PARTNER 3 trial, 495 patients with severe symptomatic aortic stenosis underwent TAVR with the SAPIEN 3 valve. The use of predilation was left to operator discretion. The primary end point was a composite of all-cause death, stroke, or rehospitalization. Secondary end points included valve hemodynamic performance and the need for postdilation. Propensity score matching was performed. RESULTS: Predilation and direct TAVR were performed in 286 (57.8%) and 209 (42.2%) patients, respectively. Before matching, the primary end point occurrence at 30 days (3.8% versus 4.8%, P=0.604) and 1 year (8.7% versus 8.1%, P=0.831) was similar in the predilation versus direct TAVR groups. Similar results were observed after matching (202 patients in each groups). Incidence of ≥ mild paravalvular regurgitation was similar in both groups. Incidence of severe prosthesis-patient mismatch was low but higher in the predilation group versus the direct TAVR group (8.2% versus 2.6%, P=0.023). Compared with direct TAVR, the use of predilation was associated with longer procedure duration (63.2 versus 51.4 minutes, P=0.001), while the rate of postdilation did not differ between the 2 groups (24.8% versus 18.8%, P=0.150). CONCLUSIONS: Predilation and direct TAVR are safe in patients with low surgical risk and favorable aortic valve anatomy. Direct TAVR decreased the procedure duration and did not predispose to more postdilation.


Posted July 15th 2021

Off-pump myocardial revascularization with Impella 5.5-assisted for cardiogenic shock.

Giuseppe Tavilla M.D. Ph.D.

Giuseppe Tavilla M.D. Ph.D.

Tavilla, G., Beckles, D.L., Morris, P. and Reddy, R.C. (2021). “Off-pump myocardial revascularization with Impella 5.5-assisted for cardiogenic shock.” J Card Surg Jun 30. [Epub ahead of print].

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We report a case of Impella 5.5-assisted off-pump coronary artery bypass grafting for acute myocardial infarction with cardiogenic shock. The Impella 5.5 was placed in the left ventricle during the emergent procedure, and an off-pump coronary artery bypass grafting was successfully performed with exposure of all three walls of the heart. Our findings demonstrated the feasibility of off-pump coronary revascularization in three-vessel disease in a patient assisted with an Impella 5.5 percutaneous left ventricular assist device without displacement of the device during the entire perioperative period.


Posted July 15th 2021

Influence of study discontinuation during the run-in period on the estimated efficacy of sacubitril/valsartan in the PARAGON-HF trial.

Milton Packer M.D.

Milton Packer M.D.

Suzuki, K., Claggett, B., Minamisawa, M., Packer, M., Zile, M.R., Pfeffer, M.A., Chiang, L.M., Lefkowitz, M., McMurray, J.J.V., Solomon, S.D. and Desai, A.S. (2021). “Influence of study discontinuation during the run-in period on the estimated efficacy of sacubitril/valsartan in the PARAGON-HF trial.” Eur J Heart Fail Jun 11. [Epub ahead of print].

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AIMS: The 4822 patients randomized in the PARAGON-HF trial were a subset of 5746 initially eligible patients who entered sequential run-in periods. We identified patient factors associated with study discontinuation during the run-in period and estimated the implications of these discontinuations for the overall study result. METHODS AND RESULTS: We utilized multivariable logistic regression models to identify patient factors associated with study discontinuation during the run-in period. The efficacy of sacubitril/valsartan in a broader cohort approximating the full run-in population was estimated by weighting randomized patients according to the inverse probability of run-in completion. A total of 924 (16.1%) subjects failed to complete the run-in period. In multivariable models, non-completion was associated with region other than Central Europe, lower systolic blood pressure, lower serum sodium, lower haemoglobin, lower estimated glomerular filtration rate, higher N-terminal pro-B-type natriuretic peptide, higher New York Heart Association functional class, prior heart failure (HF) hospitalization, and lack of prior use of renin-angiotensin system inhibitors or beta-blocker. In repeat analysis of the effect of randomized treatment in PARAGON-HF giving greater weight to participants resembling those who failed to complete the run-in period, the incidence of HF hospitalizations and cardiovascular death was higher, and sacubitril/valsartan treatment reduced the composite of total HF hospitalizations and cardiovascular death compared with valsartan (rate ratio 0.86; 95% confidence interval 0.74-1.00). CONCLUSION: Patients with more advanced HF were at higher risk for non-completion of the run-in period in PARAGON-HF. Re-analysis of study outcomes accounting for the effect of run-in non-completion did not alter the estimated treatment effects of sacubitril/valsartan vs. valsartan.


Posted July 15th 2021

Severe Mitral Paravalvular Leak Treated with Percutaneous Paravalvular Leak Closure with Underlying Severe Mitral Annular Calcium.

James W. Choi M.D.

James W. Choi M.D.

Sudhakaran, S., Tandon, A., Rafael, A.E. and Choi, J.W. (2021). “Severe Mitral Paravalvular Leak Treated with Percutaneous Paravalvular Leak Closure with Underlying Severe Mitral Annular Calcium.” Am J Cardiol Jun 20;S0002-9149(21)00425-2. [Epub ahead of print].

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Standard operative mitral valve replacement for mitral stenosis in the setting of severe mitral annular calcium has been associated with increased morbidity and mortality. Inability to ensure a well seated prosthesis may lead to periprosthetic leak. We present a case of severe paravalvular leak, causing significant hemolysis, after mitral valve replacement with underling severe mitral annular calcium. The leak was successfully repaired using a transseptal percutaneous approach, with subsequent resolution of hemolysis.