Patient Centered.

Data Driven.

2022 ANNUAL REPORT

Message from
OUR Co-Directors

The CVC has long realized that clinical research is a team sport and has fostered an environment in which clinicians work in close collaboration with epidemiologists and statisticians. More recently, our team has expanded to include data scientists with expertise in artificial intelligence and machine learning. Although the volume, velocity, and variety of health data is constantly evolving, the fundamental focus of our research has remained steadfast: to improve the care and outcomes of patients with cardiovascular disease. The theme of the CVC’s 2022 Annual Report - “Patient Centered. Data Driven” - reflects this commitment...

Perhaps nothing is more patient-centered than advice on food and diet! The SODIUM-HF trial, an international pragmatic randomized clinical trial led by Dr. Justin Ezekowitz, examined the impact of salt intake in patients with heart failure. The trial enrolled 806 patients in 6 countries and compared reducing dietary sodium intake to usual care. The study found that while a dietary intervention to reduce sodium intake did not reduce hospitalization or emergency department visits, it was associated with some improvement in patient quality of life and functional status. Additional information about SODIUM-HF can be found here.

The consequences of COVID-19 continue to be of interest to patients, the public, healthcare providers, and policy-makers. Fostered by the Canadian Cardiovascular Research Collaboratory (C3), the CORONA project has brought together researchers from Alberta and Ontario to examine the impact of COVID-19 in the two provinces. Dr. Finlay McAlister and colleagues examined the health records of 800,000 people who tested positive for SARS-CoV-2 in 2020-21 to identify patients who were hospitalized for COVID-19. Of the patients who were hospitalized, approximately 1 in 5 died during the COVID-19 hospitalization, and an additional 1 in 10 were readmitted to hospital or died within 30 days. Data such as these inform healthcare decisions in Canada and beyond. Additional information on the characteristics of the patients who were more likely to have these adverse outcomes can be found here.

Early identification and treatment of individuals at high risk for cardiovascular disease, such as those with diabetes, are key to improving patient outcomes. Accordingly, as part of the REDISCOVER project, Dr. Padma Kaul and colleagues examined adherence to diabetes screening guidelines among 1.4 million residents of Alberta and found sub-optimal rates, especially among young males. These data can be used to raise awareness in this high-risk group and develop strategies for preventing diabetes and cardiovascular complications that arise later in life. More information about this study can be found here.

One often forgets that Sir Arthur Conan Doyle, creator of one of the most famous sleuths in history, was a physician. His stories of Holmes and Watson demonstrate the value of teamwork and the importance of collecting and analyzing data before arriving at conclusions that were anything but elementary! We hope you agree that our annual report, which shows how the CVC is continuously using data to inform patient care and improve outcomes, echoes these sentiments.

The CVC Co-Directors,

Justin Ezekowitz,

MBBCh, MSc

Shaun Goodman,

MD, MSc

Padma Kaul,

PhD

“It is a capital mistake to theorize before one has data.”

ABOUT THE CVC

The Canadian VIGOUR Centre (CVC) was established in 1997 as an academic research organization (ARO) at the University of Alberta, and has since been committed to the enhancement of cardiovascular health. The CVC is recognized for its pioneering research in cardiovascular medicine, which embraces the translation of research through thought leadership and management of innovative clinical trials. Furthermore, the CVC is focused on the generation of new knowledge from patient registries and population outcome studies, which inform the direction of future pathways.

As an ARO, the CVC is committed to the scholarly value of scientific inquiry and truth, and believes knowledge should be shared openly in an ethical research environment. The CVC’s dedication to lifelong learning has also inspired one of our central tenets –engaging the next generation of health professionals in a research culture that embraces curiosity, welcomes new ideas, and seeks to address key unanswered questions in health care. Learn more about the CVC’s vision, mission, and core values here.

Our Team

The CVC is anchored by a dedicated group of internationally recognized thought leaders in cardiovascular medicine and clinical investigation, and is supported by accomplished administrative and clinical operations teams, as well as experienced biostatisticians, data and machine analysts, and core laboratories personnel. Research is a team sport, and our diverse and multidimensional group is committed to continuous innovation that has an impact on informing health policy.

“Hiding within those mounds of data is knowledge that could change the life of a patient, or change the world.”

year at a glance

2022 by the Numbers

161 Publications produced by CVC faculty, staff, and trainees
29 Current studies
(clinical trials, registries, and population health and data science studies)
0
Active sites participating in CVC-managed trials
0
Citations generated from CVC-authored papers published between 2018 - 2022
0
ECGs analyzed by the CVC Core Laboratory

2+ Million

Digital ECGs analyzed by the AI/ML group

6+ Million

Canadians represented in the CVC’s data repository

New Associate Faculty Members:
Drs. David Collister and Jason Weatherald

The CVC is pleased to announce the addition of two new associate faculty members.

Dr. David Collister is a nephrologist at the University of Alberta Hospital and an Assistant Professor in the Department of Medicine at the University of Alberta. His research focuses on randomized controlled trials and prospective observational studies in chronic kidney disease and dialysis, precision medicine approaches to uremic symptoms and cognition, and the intersection of kidney disease with gender-diverse populations.

Dr. Jason Weatherald is a pulmonologist at the University of Alberta Hospital and Mazankowski Alberta Heart Institute, and an Associate Professor in the Department of Medicine at the University of Alberta. His research interests include risk assessment in pulmonary arterial hypertension, use of clinical registries and real-world data for patient-oriented research, and use of adaptive trial designs for the investigation of right heart failure interventions.

“The core advantage of data is that it tells you something about the world that you didn’t know before.”

The Next Generation of Health Researchers

As a learning organization, one of the CVC’s central tenets is to engage the next generation of health professionals in a research culture that embraces curiosity, welcomes new ideas, and seeks to address key unanswered questions that are likely to alter the minds and actions of all those involved in health care delivery. The CVC recognizes that a research experience can be life changing, whether during a summer studentship, an elective experience in clinical medicine, or through dedicated graduate or postdoctoral training. Irrespective of an individual trainee’s career plans, exposure to research galvanizes the development of a more critical mind that can then be applied to the unending search for better health solutions. In this section some of our recent trainees reflect upon their research highlights and experience collaborating with the CVC in 2022.

Frederikke Lihme, MD PhD Candidate, Statens Serum Institut

Dr. Padma Kaul is a very inspiring and passionate researcher and I have enjoyed learning from her during my time at the CVC. While working with the large group of experts at the CVC, I had the opportunity to work on my skills in medical research, teamwork, and biostatistics. I really appreciate the insights into how the Alberta health care system and registries work, and I will be able to bring these experiences and ideas home to Denmark.

Manisimha Manthena, BTech CCE Undergraduate Student, Manipal Institute
of Technology


Last summer, I had the opportunity to intern at the CVC. It was my first time in Canada, and I couldn’t have asked for a better experience. I worked under the mentorship of Dr. Sunil Vasu Kalmady and Dr. Padma Kaul on a project related to federated learning on ECG signals. The project was fascinating and challenging, and my mentors were extremely kind and helpful. I am grateful for the opportunity to have gained valuable knowledge and experience while exploring the beautiful country of Canada.

Haran Yogasundaram, MD, MScCardiology Fellow, University of Alberta

My research at the CVC has allowed me to learn from some of the brightest and most accomplished researchers in the field of cardiovascular medicine. This process has prepared me for the future transition to independent research with the ultimate goal of improving the lives of patients suffering from cardiovascular disease.

“The important thing in science is not so much to obtain new facts as to discover new ways of thinking about them.”


Dr. Justin Ezekowitz Named Canadian Heart Failure Society President

In November 2022, CVC Co-Director Dr. Justin Ezekowitz was announced as the new President of the Canadian Heart Failure Society (CHFS). The CHFS provides a platform for cardiovascular professionals to improve patient care through research, advocacy, and education.

Research
Highlights

In order to establish the present landscape of cardiogenic shock care in Canada, Drs. Sean van Diepen and Shaun Goodman, in collaboration with the Canadian Cardiovascular Research Collaboratory (C3) Cardiogenic Shock Working Group, conducted a nation-wide survey on cardiogenic shock management and processes-of-care in centers with cardiac catheterization laboratories. The collected survey data included hospital characteristics, case volumes, physician specialities managing cardiogenic shock, availability of multi-disciplinary shock teams and shock protocols, use of mechanical circulatory support, and perceived challenges to care. This report identified substantial variations, in practice patterns for cardiogenic shock across Canadian hospitals, as well as pre-existing challenges unique to Canadian practice. These results highlight the potential need for greater development of regional cardiogenic shock networks, protocols to standardize care practices, and clinical research.
The SODIUM-HF trial, led by principal investigator Dr. Justin Ezekowitz, was presented as a Late-Breaking Clinical Trial at the American College of Cardiology Scientific Session in 2022, and was simultaneously published in The Lancet. The study was designed as a pragmatic trial to assess the effects of sodium reduction on clinical outcomes in a heart failure (HF) population.

SODIUM-HF enrolled a total of 806 patients across 26 sites in 6 countries. 397 patients were randomized to the low sodium diet and followed a dietary intervention designed to reduce sodium intake to <1500 mg/day, while the other 409 patients were randomized to usual care and followed local guidelines. The total intervention period was 12 months, and patients were followed for an additional 12 months. Dietary sodium intake was assessed using a 3-day food record, which were analyzed by trained personnel in a core lab using a nutrient software program.

The study team found that, in patients with HF, a dietary intervention to reduce sodium intake did not reduce clinical events, such as hospitalization and emergency department visits. However, modest improvements were observed in patient-reported quality of life and New York Heart Association functional class. SODIUM-HF is the largest trial of its type to date and provides a major update to published evidence.
Diabetes Canada guidelines recommend that everyone over the age of 40 undergo screening for diabetes at least once every 3 years. This publication examined adherence to these guidelines among both males and females after accounting for age, urban/rural residence, and material deprivation. The authors also sought to determine the rate of prediabetes and diabetes among adherent and non-adherent individuals.

This research utilized Alberta public health data to track diabetes screening rates in approximately 1.4 million patients (aged 40-79) without pre-existing diabetes or cardiovascular disease in April 2013. Adherence for the duration of a 3-year screening period (2013–2016) and prediabetes and diabetes during a 4-year follow-up period were examined.

The authors found that adherence to these guidelines is sub-optimal, especially among younger males in their 40s. Additionally, despite having lower rates of adherence to screening, they found that males have higher rates of prediabetes and diabetes compared to females. The authors stress the need for additional public health campaigns to raise awareness and improve diabetes screening rates in young adults, particularly males.

This is the first publication from the REDISCOVER study, which aims to provide new insights into the relationship of sex and diabetes on cardiovascular disease outcomes. The study is led by Dr. Padma Kaul as part of her role as the Canadian Institutes of Health Research Sex and Gender Science Chair.

Prompt reperfusion with primary percutaneous coronary intervention (pPCI) improves clinical outcomes in patients suffering a ST-elevation myocardial infarction (STEMI); however, it has been recognized that reperfusion therapies can result in adverse events known collectively as reperfusion injury.

The SONOSTEMI study, led by Dr. Kevin Bainey, was a prospective, single-centre, single-arm study of STEMI patients presenting within 6 hours of chest pain who will require pPCI. This first North American proof-of-concept study evaluated the effects of sonothrombolysis on epicardial patency, myocardial perfusion, and left ventricular performance in STEMI.

A high rate of ≥50% ST-segment resolution post-PCI (greater than expected in STEMI) was observed, as well as a notable enhancement in left ventricular performance at 3 months in 80% of patients. These noteworthy results provide further data to support this novel technique in augmenting reperfusion in STEMI, which seem to translate to enhanced left ventricular performance. These hypothesis-generating findings require further confirmation from a randomized trial enrolling patients with short ischemic times.

Although COVID-19 hospital admissions have received a great deal of focus, relatively little attention has been paid to the post-discharge period. In this publication, Dr. Finlay McAlister and his fellow CORONA collaborators explored possible factors that may lead to some hospitalized COVID-19 patients being readmitted or dying within a month of discharge.

The records of adult patients hospitalized for COVID-19 in Ontario and Alberta from the start of 2020 to September 2021, showed that of the more than 800,000 people who tested positive for SARS-CoV-2, 5.5% needed hospital care. Of these, 18.3% died in hospital. Among those discharged, 11% were either readmitted or died within 30 days. These patients were generally older, had a higher Charlson comorbidity burden, more likely to be male, more likely to be discharged home with home care or to a long-term care facility, and had higher rates of more frequent hospitalizations or emergency department visits. Of the patients admitted with COVID-19, 91% of those in Alberta and 95% in Ontario were unvaccinated.

These post-discharge event rates were similar after admissions for COVID-19 as with other medical causes of hospital admission before the pandemic. Although outcome rates were similar in Alberta and Ontario, the discrimination performance of the LACE score for post-discharge readmission or death was suboptimal in COVID-19 survivors. Prediction performance was improved by including sex, discharge locale, and socioeconomic status in the model.

Cardiac amyloidosis is a condition caused by a buildup of amyloid proteins in the heart, which can impact its functionality and eventually cause heart failure. Although awareness of cardiac amyloidosis has increased among clinicians, neither its incidence nor prevalence are well-described in a community setting. In this study, Drs. Nariman Sepehrvand, Cindy Westerhout, Finlay McAlister, Padma Kaul, Justin Ezekowitz, and fellow coauthors, examined the incidence and prevalence of cardiac amyloidosis in the community.

This population-based study utilized administrative data from Alberta’s regional health authority (Alberta Health Services) to identify patients with probable and possible cardiac amyloidosis among all who had health system encounters in Alberta from 2004 to 2019. The authors found that the incidence and prevalence of cardiac amyloidosis may be higher than previously thought. Further, while the incidence rate of probable cardiac amyloidosis increased, the mortality decreased, likely due to earlier detections through non-invasive techniques, and there was a general increase in the prevalence rates over the decade of observation. Lastly, an at-risk population was identified using the phenotypes frequently associated with cardiac amyloidosis. However, this phenotype approach yielded a cohort that was too large to be amenable for effective screening.

Given the emergence of new therapies for cardiac amyloidosis and the high costs linked to these therapies, this research highlights the importance of developing strategies to screen, identify, and track patients with cardiac amyloidosis from administrative databases.

The VICTORIA trial randomized patients with heart failure with reduced ejection fraction (HFrEF) to vericiguat or placebo and found that vericiguat reduced the primary composite end point of cardiovascular death or hospitalization for HF. A prior prespecified subgroup analysis examined the efficacy of vericiguat according to quartiles of N-terminal pro-B-type natriuretic peptide (NT-proBNP) at randomization and revealed a significant treatment interaction with the primary endpoint, suggesting less benefit for patients in the highest quartile of NT-proBNP.

In this study, Drs. Paul W. Armstrong, Cindy Westerhout and Justin Ezekowitz, Yinggan Zheng, and fellow coauthors, sought to determine whether a relationship exists between sequential changes in the prognostically relevant biomarker NT-proBNP and clinical outcomes in this high-risk population of patients with HFrEF. Importantly, the effect of vericiguat on changes in NT-proBNP and an association between vericiguat’s treatment effect on clinical outcomes were also explored.

In this large population of nearly 5,000 patients with worsening HFrEF, a strong correlation between changes in NT-proBNP and the subsequent occurrence of cardiovascular death and HF hospitalization was demonstrated in both study arms. Furthermore, vericiguat produced a greater overall decline in NT-proBNP than placebo, which appears associated with the modest relative clinical benefit of vericiguat therapy.

There is increasing recognition that significant sex differences exist across the spectrum of atrial fibrillation (AF). While the lifetime risk of developing AF is slightly lower in women than men, the absolute number of women with AF is higher due to significant differences in overall longevity. Women with AF experience more symptoms and may experience worse outcomes compared to men. Since the emergency department (ED) is a common point of first contact for patients who experience a new AF episode, it may provide the optimal setting to address possible care gaps among sexes.

In this study, Sunjidatul Islam, Drs. Douglas Dover, Padma Kaul, and Roopinder Sandhu, with their coauthors, examined sex differences in oral anticoagulation use and adherence, as well as adverse outcomes after discharge, including stroke, heart failure, and all-cause mortality, in a large population-based cohort of patients presenting to the ED with a new AF presentation. The authors further examined whether the sex differences in the management and outcomes of oral anticoagulants differed according to whether the patients was discharged from the ED or admitted to the hospital.

This research demonstrated guideline-indicated use of oral anticoagulants was lower in females discharged home than in males; however, the females who were initiated had better adherence than males. In one-year follow-up, females admitted to the hospital were at a significantly higher risk of developing stroke.
The AUGUSTUS trial included patients with atrial fibrillation (AF) and a recent acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI) treated with an antithrombotic regimen consisting of apixaban and a P2Y12 inhibitor, without aspirin. The trial demonstrated a lower risk of bleeding and hospitalization and a similar risk of ischemic events compared to regimens that included vitamin K antagonists (VKAs), aspirin, or both. Choosing the optimal antithrombotic therapy in patients with AF and an ACS and/or PCI remains challenging and can be affected by prior oral anticoagulant (OAC) treatment. Therefore, Drs. Robert Welsh, Shaun Goodman, and fellow coauthors, undertook a prespecified subgroup analysis of the AUGUSTUS trial, and explored the patient characteristics, clinical events, and potential interaction with randomized treatment arms comparing patients with or without prior OAC use. This analysis showed that, although patients enrolled in AUGUSTUS with prior OAC use had increased comorbidities, they had no increased risk of bleeding complications and had lower risk of ischemic events. Clinicians can confidently apply the results of the AUGUSTUS trial to patients with AF and ACS and/or elective PCI, regardless of their prior OAC status.
In 2022, the Canadian Cardiovascular Society (CCS) published new guidelines for peripheral arterial disease (PAD). CVC Associate Faculty Member, Dr. Sean McMurtry, a primary panel author on this publication, speaks about the risk factors, symptoms, treatment, and public health impact of PAD below.

Compared with other cardiovascular diseases there is generally less public awareness of PAD. Can you briefly describe what PAD is? While the term PAD sometimes is used in a general way to denote the set of artery diseases that affect arteries other than the coronary artery tree, most people use the term to mean atherosclerotic lower extremity PAD. Atherosclerotic lower extremity PAD is atherosclerotic plaques that occur in the leg arteries, and are similar to those that cause coronary artery disease. These plaques are caused by the same risk factors, including smoking, high cholesterol, diabetes, and high blood pressure. While often the plaques do not block the arteries enough to cause symptoms, many people with PAD have claudication, or pain in the legs when they walk, pain at rest, or skin breakdown with ulcers or gangrene. In addition to having problems with leg pain or even leg wounds, people with PAD are at high risk for heart attacks and strokes since they usually have atherosclerotic plaques in other places, too.

In your opinion, what are the top 3 unmet needs for patients with PAD?

Recognition
Often people with PAD do not know they have it. They may have no symptoms yet, or they may have minor or unusual symptoms. This is important, since they may be at high risk for heart attacks or strokes, or have elevated risk for developing leg wounds that can lead to amputation. PAD is diagnosed with a test called the ankle brachial index (ABI), and patients with leg pain with walking or leg wounds may need an ABI to know whether they have PAD or not.
Adequacy of medical treatment
Studies in Canada and elsewhere have consistently shown that the medical treatment of people with PAD has gaps, and people are living with preventable risk for worsening PAD as well as heart attacks and strokes. All caregivers who look after people with PAD should collaborate to improve medical treatment for these high-risk people so they have longer and healthier lives.
Adoption of new treatments
While most caregivers know that people with PAD should quit smoking, and have their cholesterol, high blood pressure, or diabetes treated, and that people with symptomatic PAD should be on aspirin, there are new treatments that can save lives and limbs when added on to other treatments. For example, people with PAD and diabetes do better when they also take a sodium-glucose cotransporter 2 (SGLT2) inhibitor. Similarly, most people with symptomatic PAD are likely to do better when they take the anticoagulant rivaroxaban in addition to aspirin. Making sure that the best new treatments are used can help people with PAD have longer and healthier lives.
What is the current public health impact of PAD in Canada? The incidence of PAD in Canada is approximately 200 per 100,000 for males and 170 per 100,000 for females. This translates into tens of thousands of new cases of PAD every year. These people are at a higher risk of having a major cardiovascular event or dying. This means there are thousands of Canadians who are hospitalized or die from PAD-associated problems each year.

What are some of the key recommendations from the CCS 2022 Guidelines for PAD? There are many important recommendations, but from my perspective the highlights include:

  1. Using an ABI and/or a toe-brachial index study to confirm the diagnosis of PAD in patients with symptoms of PAD;
  2. Smoking cessation to prevent PAD, and prevent major adverse cardiovascular events (MACE) and major adverse limb events in patients with PAD;
  3. Patients with PAD and type 2 diabetes should be offered an SGLT2 inhibitor, compared with the usual diabetic control, because of the reduction in MACE without any risk of increased amputation; and
  4. A treatment of rivaroxaban, in combination with aspirin, for the management of patients with symptomatic lower extremity PAD at high risk for ischemic events, and/or high-risk limb presentation post-peripheral revascularization, and at low bleeding risk.
The first of these highlights the importance of recognition, and the second highlights the importance of smoking cessation as the cornerstone of management. The third and fourth are recommendations about adding new medical therapies that are proven to save lives and limbs.

Acknowledgements

The CVC gratefully acknowledges and thanks:

  • The patients, for their willing participation in our trials and registries. They are the true heroes of clinical research and we honor their volunteer spirit.
  • The CVC faculty, external advisors, and collaborators for their enriching contributions and for providing ongoing research opportunities. We look forward to providing continued support and to future collaborations in advance of our mission.
  • The CVC staff and management for their outstanding dedication, professionalism, excellent contributions, and ingenuity, which enhances the quality of our research work.
  • Our trainees for their commitment, ideas, and enthusiasm. You are the next generation of researchers and health care providers.
  • The sponsors and granting agencies; without their generous financial support our research and educational activities would not be possible.
  • The excellent work of our communications group for their time and the dedication required to produce this report.
  • The team at AM/FM for the concept and design.
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