Best Cardiovascular Clinical Science of the Decade Award Nominations

Nomination 1

Husain, M., Birkenfeld, A. L., Donsmark, M., Dungan, K., Eliaschewitz, F. G., Franco, D. R., Jeppesen, O. K., Lingvay, I., Mosenzon, O., Pedersen, S. D., Tack, C. J., Thomsen, M., Vilsbøll, T., Warren, M. L., & Bain, S. C. (2019). Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. New England Journal of Medicine, 381(9), 841–851. https://doi.org/10.1056/nejmoa1901118

Bibliometrics (Citations per Year)* – 226.33

Bibliometrics (Field-Weighted Citation Impact)* – 82.82

This paper received three nominations. Below are all nomination blurbs:

1. Husain et al’s evaluation of oral semaglutide in the landmark PIONEER 6 trial (NEJM 2019) represented a paradigm shift in the management of type 2 diabetes and cardiovascular risk. This rigorous, multicenter, randomized, double-blind trial was the first to establish the cardiovascular safety of an oral GLP-1 receptor agonist in patients at high cardiovascular risk, demonstrating non-inferiority to placebo for major adverse cardiovascular events (MACE) and a notable reduction in cardiovascular and all-cause mortality. The study’s innovative oral formulation addressed a major barrier to GLP-1 therapy—injectable delivery—broadening access and acceptance among patients and clinicians. Since publication, this paper has received >1800 citations (>300 per year) and has been widely covered in major medical and lay media, directly influencing international diabetes and cardiology guidelines and accelerating the adoption of oral GLP-1 therapy worldwide. This manuscript exemplifies methodological excellence, clinical relevance, and transformative impact in cardiovascular science.

2. Dr. Mansoor Husian’s landmark study, published in the New England Journal of Medicine and cited over 1000 times, represents a major advance in cardio-diabetes research. This large-scale, international, randomized controlled trial enrolled 3183 patients with cardiovascular disease across 214 sites in 21 countries to evaluate oral semaglutide as an effective and safe alternative for cardiovascular risk reduction in type 2 diabetes. The trial demonstrated that oral semaglutide was noninferior to placebo, ruling out an 80% excess cardiovascular risk. By providing an oral alternative of a GLP-1 receptor agonist, traditionally administered subcutaneously, the study broadened therapeutic options and may mitigate concerns surrounding injections for both patients and clinicians. Husain et al.’s work marks a milestone in diabetes management, reinforcing the integration of cardiovascular risk reduction into comprehensive diabetes care and shaping future therapeutic strategies.

3. The landmark PIONEER 6 trial, published in The New England Journal of Medicine in 2019 [1814 citations], demonstrated the cardiovascular safety of the first oral GLP-1 receptor agonist (GLP-1RA) Semaglutide in high-risk adult patients. The study met its primary endpoint of non-inferiority, ruling out excess cardiovascular risk and also showed a significant reduction in cardiovascular causes of mortality. This work had immediate clinical impact by expanding therapeutic options beyond only having approval for injectable GLP-1RA drugs, paving the way for a successful U.S. Food and Drug Administration and Health Canada approval of orally administered Semaglutide for type 2 diabetes in adults. This study continues to be impactful, serving as the foundation for an ongoing FDA review in 2025 to expand the indication of oral Semaglutide to include reducing the risk of major adverse cardiovascular events. This trial redefined the landscape of options for advanced cardiometabolic therapeutics in Canada and globally.

Nomination 2

Lee, D. S., Lee, J. S., Schull, M. J., Borgundvaag, B., Edmonds, M. L., Ivankovic, M., McLeod, S. L., Dreyer, J. F., Sabbah, S., Levy, P. D., O’Neill, T., Chong, A., Stukel, T. A., Austin, P. C., & Tu, J. V. (2019). Prospective validation of the emergency heart failure mortality risk grade for acute heart failure. Circulation, 139(9), 1146–1156. https://doi.org/10.1161/CIRCULATIONAHA.118.035509

Bibliometrics (Citations per Year)* – 15.33

Bibliometrics (Field-Weighted Citation Impact)* – 3.88

The ACUTE study prospectively validated the EHMRG multivariable risk score for 7-day and 30-day mortality in a multicentre evaluation. With support of CIHR grants, we conducted a large-scale provincial clinical chart review and derived and internally validated the EHMRG risk scores using bootstrap resampling. Here, we prospectively validated the EHMRG models in emergency departments to assess its performance in a real-world setting in 2000+ patients. Both the 7-day and 30-day models stratified mortality risk and were particularly effective in identifying low risk patients, with 0% mortality rates in the lowest two quintiles of the EHMRG 7-day score and the lowest quintile of the EHMRG 30-day score. Although the EHMRG models were not used to dictate patient disposition in this study, the mathematical models were superior to physician estimated risk: the discrimination was 0.81 for the EHMRG-7 score and 0.71 for physician estimated risk. This prospective validation preluded the COACH trial.

Nomination 3

Lee, D. S., Straus, S. E., Farkouh, M. E., Austin, P. C., Taljaard, M., Chong, A., Fahim, C., Poon, S., Cram, P., Smith, S., McKelvie, R. S., Porepa, L., Hartleib, M., Mitoff, P., Iwanochko, R. M., MacDougall, A., Shadowitz, S., Abrams, H., Elbarasi, E., … Ross, H. J. (2023). Trial of an Intervention to Improve Acute Heart Failure Outcomes. New England Journal of Medicine, 388(1), 22–32. https://doi.org/10.1056/nejmoa2211680

Bibliometrics (Citations per Year)* – 49.5

Bibliometrics (Field-Weighted Citation Impact)* – 23.56

This paper received three nominations. Below are all nomination blurbs:

1. The COACH trial, published in the NEJM, a widely reputable and influential journal, was recognized as one of the top 10 papers in heart failure and cardiomyopathies in 2023 by the European Heart Journal and has been cited over 120 times. This collaborative stepped-wedge, cluster-randomized trial enrolled 5,452 patients and was conducted at 10 Ontario hospitals to evaluate a validated, point-of-care risk stratification algorithm for patients with acute heart failure to lower adverse outcomes. By assisting in making better-informed decisions and tailored cardiovascular care, the intervention helped optimize health resource utilization and improve clinical outcomes. Specifically, by reducing inappropriate discharge of high-risk patients and increasing early discharge of low-risk patients coupled with rapid outpatient follow-up. The COACH trial’s proposed intervention significantly reduced the risk of cardiovascular hospitalization and death at both 30 days and 20 months, showcasing the importance of providing the right care to each patient to improve outcomes.

2. This stepped wedge cluster RCT examined the use of the EHMRG prediction model coupled with a strategy of early discharge for low risk patients and hospital admission for high risk patients on clinical outcomes. Low risk patients who were discharged early were followed in a rapid outpatient ambulatory clinic, which was nurse-run and cardiologist supervised. The final results of the Comparison of Outcomes and Access to Care for Heart failure (COACH) trial, published in NEJM, demonstrated that using the validated EHMRG risk score to guide disposition decisions in the emergency department reduced the risks of death or cardiovascular hospitalization by 12% within 30 days of presentation, and by 5% during extended 20-month follow-up. This trial was the first strategic trial that demonstrated improved outcomes of acute heart failure within an early timeframe, and provided proof-in-principle that using a mathematical risk score can improve clinical outcomes when applied at the bedside.

3. This study, “Trial of an Intervention to Improve Acute Heart Failure Outcomes,” exemplifies scientific rigor through its innovative design and execution. Conducted as a stepped-wedge, cluster-randomized trial across 10 Ontario hospitals, it tested a hospital-wide strategy integrating a validated risk stratification tool (EHMRG30-ST) with structured outpatient follow-up. With over 5,400 patients enrolled and outcomes captured through robust, linked administrative data, the study demonstrated a significant reduction in 30-day mortality or cardiovascular hospitalization.
Its methodological strengths include real-world applicability, minimal loss to follow-up, and risk-adjusted analyses that enhance generalizability. Scientifically, it sets a new standard for embedding evidence-based tools into emergency care pathways. Clinically, it offers a safe, scalable alternative to routine hospitalization by addressing a long-standing challenge in acute heart failure management. This trial advances both the science and delivery of cardiovascular care and stands as a model for health systems innovation.

Nomination 4

Marwick, T. H., Dewar, E., Nolan, M., Shirazi, M., Dias, P., Wright, L., Fitzgerald, B., Kearney, L., Srivastava, P., Atherton, J., Negishi, K., Sverdlov, A. L., Wahi, S., Otton, J., Selvanayagam, J., Thomas, L., & Thavendiranathan, P. (2024). Strain surveillance during chemotherapy to improve cardiovascular outcomes: the SUCCOUR-MRI trial. European Heart Journal, 45(41), 4414–4424. https://doi.org/10.1093/eurheartj/ehae574

Bibliometrics (Citations per Year)* – 13

Bibliometrics (Field-Weighted Citation Impact)* – 5.05

Published in the European Heart Journal, SUCCOUR-MRI was a prospective, international, randomized controlled trial that was a collaborative effort involving 14 sites to assess the impact of initiating cardioprotective therapy in patients with decreased global longitudinal strain (GLS) undergoing chemotherapy. Advancing the understudied field of cardio-oncology, the SUCCOUR-MRI trial validated the benefits of surveilling GLS. The study revealed that chemotherapy patients with reduced GLS who received cardioprotective therapy had increased preservation of their 12-month MRI-left ventricle ejection fraction compared to patients who received standard care. The SUCCOUR-MRI trial emphasizes the importance of developing and implementing cardiovascular risk stratification tools, such as monitoring GLS, to aid in the prevention of chemotherapy-related cardiotoxicity without compromising regular cancer treatment. This is the largest imaging trial in the field to date, and was highlighted as one of the top 10 studies in the field of Cardio-Oncology by the community in 2024.

Nomination 5

Miron A, Lafreniere-Roula M, Steve Fan CP, Armstrong KR, Dragulescu A, Papaz T, Manlhiot C, Kaufman B, Butts RJ, Gardin L, Stephenson EA, Howard TS, Aziz PF, Balaji S, Ladouceur VB, Benson LN, Colan SD, Godown J, Henderson HT, Ingles J, Jeewa A, Jefferies JL, Lal AK, Mathew J, Jean-St-Michel E, Michels M, Nakano SJ, Olivotto I, Parent JJ, Pereira AC, Semsarian C, Whitehill RD, Wittekind SG, Russell MW, Conway J, Richmond ME, Villa C, Weintraub RG, Rossano JW, Kantor PF, Ho CY, Mital S. A Validated Model for Sudden Cardiac Death Risk Prediction in Pediatric Hypertrophic Cardiomyopathy. Circulation. 2020 Jul 21;142(3):217-229. doi: 10.1161/CIRCULATIONAHA.120.047235. Epub 2020 May 18. PMID: 32418493; PMCID: PMC7365676.

Bibliometrics (Citations per Year)* – 35

Bibliometrics (Field-Weighted Citation Impact)* – 8.77

In 2017, Mital established an international research network, Precision Medicine in Cardiomyopathy (PRIMaCY), involving 20 centres across Canada, USA, and Australia. Mital developed and published the first fully validation prediction model for sudden cardiac death in children with HCM (Miron A, Circulation-see attached pdf) garnering tremendous attention (top 5% Altmetric score) and immediate and sustained uptake by cardiologists across the world. It was incorporated and published in the 2020 & 2024 AHA/ACC and 2024 CCS clinical practice guidelines. as an individualized risk assessment tool to guide patient ICD shared decision making. The tool was licensed to MDCalc and to the AHA and made available as a web application, a mobile application, and as the first Epic-integrated app in Nov 2021. Through CIHR funding, the tool has since been launched in CHEO, Stollery Children’s Hospital, and Children’s Hospital of Philadelphia. It has been a practice-changing milestone in HCM care.