Featured Publications

As a learning organization committed to enhancing the health of current and future generations through research, the CVC relentlessly pursues the generation, translation, and dissemination of new knowledge addressing unmet clinical needs. This section highlights important publications produced by the CVC faculty and our body of research in recent months.

View CVC’s full publication archive here.

Sustained Low-Density Lipoprotein Cholesterol Lowering With Alirocumab in ODYSSEY OUTCOMES.

Goodman SG, Steg PG, Szarek M, Bhatt DL, Bittner VA, Diaz R, Harrington RA, Jukema JW, White HD, Zeiher AM, Schwartz GG.
J Am Coll Cardiol. 2020;75:448-451.

In the ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, 18,924 patients with a recent acute coronary syndrome (ACS) not at lipid goals despite maximally tolerated statin therapy were randomized to alirocumab or placebo. Alirocumab produced a marked reduction of low-density lipoprotein cholesterol (LDL-C) levels and significantly reduced the primary composite cardiovascular endpoint.

The authors observed sustained LDL-C lowering without apparent attenuation over 3 years in ODYSSEY OUTCOMES participants who had all LDL-C measurements, did not discontinue alirocumab or have blinded substitution of placebo, and did not change background lipid-lowering therapy. These findings are consistent with previous, shorter-duration trials with alirocumab and indicate no clinically meaningful diminution of its lipid-lowering efficacy over several years.

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A Population-Based Study Evaluating Sex Differences in Patients Presenting to Emergency Departments With Syncope.

Bernier R, Tran DT, Sheldon RS, Kaul P, Sandhu RK.
JACC Clin Electrophysiol. 2020;6:341-347.

For patients who experience a syncope event, the emergency department (ED) is a common point of first contact with the health care system. Given that decisions made in the ED affect not only immediate but also longer-term treatment and outcomes, it is important to understand whether sex-specific differences in triage decisions and outcomes exist.

In this population-based study evaluating sex-specific differences in patients presenting to the ED with a primary diagnosis of syncope, the authors found that women were more likely than men were to present to the ED; however, women were less likely to be admitted to the hospital. Mortality rates were significantly lower for women, regardless of their discharge status, and likely reflects younger age and lower comorbidity burden.

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Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction.

Armstrong PW, Pieske B, Anstrom KJ, Ezekowitz J, Hernandez AF, Butler J, Lam CSP, Ponikowski P, Voors AA, Jia G, McNulty SE, Patel MJ, Roessig L, Koglin J, O'Connor CM; VICTORIA Study Group.
N Engl J Med. 2020;382:1883-1893.

VICTORIA is a randomized, placebo-controlled, parallel-group, multi-center, double-blind, event driven study of vericiguat (MK-1242) in participants with heart failure with reduced ejection fraction (HFrEF). This publication is the culmination of the international efforts in the VICTORIA trial. The investigators found that, in patients with worsening heart failure with reduced ejection fraction, vericiguat reduced the risk of cardiovascular death or heart failure hospitalization by 10% compared to a placebo control group.

More information about the VICTORIA trial can also be found on our website here.

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Impact of the Generic Valsartan Recall in Alberta, Canada.

McAlister FA, Youngson E.
J Am Coll Cardiol. 2020;75:1860-1862.

After N-nitrosodimethylamine, a potential carcinogen, was detected in valsartan supplied by Zhejiang Huahai Pharmaceuticals (Zhejiang, China), Health Canada issued a voluntary recall notice on July 9, 2018, for 28 generic valsartan preparations. The impact of drug recalls on health services use and patient outcomes remain uncertain.

In this article, the authors, utilizing drug dispensation data for all ages and evaluating outpatient physician clinic visits and emergency department (ED) visits and hospitalizations, examined the impact of the generic valsartan recall on patient treatment, outcomes, and health services use in Alberta.

They conclude that the recall of generic valsartan products resulted in a substantial increase in outpatient physician visits for hypertension in Alberta but no significant change in ED visits or hospitalizations for stroke and/or transient ischemic attack. This study adds to the limited published data evaluating the impact of drug recalls or shortages on both patient outcomes and on health care system utilization, an increasingly common problem that has increased >7-fold in the past decade, and deserves further examination.

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COVID-19 and Disruptive Modifications to Cardiac Critical Care Delivery

Katz JN, Sinha SS, Alviar CL, Dudzinski DM, Gage A, Brusca SB, Flanagan MC, Welch T, Geller BJ, Miller PE, Leonardi S, Bohula EA, Price S, Chaudhry SP, Metkus TS, O'Brien CG, Sionis A, Barnett CF, Jentzer JC, Solomon MA, Morrow DA, van Diepen S.
J Am Coll Cardiol. 2020;76:72-84.

The coronavirus disease-2019 (COVID-19) pandemic has presented a major unanticipated stress on our workforce, organizational structure, systems of care, and critical resource supply. In order to ensure provider safety, maximize efficiency, and optimize patient outcomes, health systems need to be agile.

This manuscript draws upon the experiences of colleagues from heavily impacted regions of the United States and Europe as well as lessons learned from military mass casualty medicine. The authors offer pragmatic suggestions on how to implement scalable models for critical care delivery, cultivate educational tools for team training, and embrace technologies such as telemedicine to enable effective collaboration despite social distancing imperatives.

Management of a disruptive illness like COVID-19 calls for disruptive health care adaptations and innovations, particularly when treating the highest risk critical care cohorts. In response, health systems need to be committed, cohesive, and innovative in order to optimize care efficiency, ensure provider safety, and improve patient outcomes.

The authors found that parental AF is associated with a higher frequency of AF, stroke/TIA, and other cardiovascular risk factors in offspring in early adulthood. They believe these findings suggest that young adults with a history of parental AF should be counseled about cardiovascular health and primary prevention maneuvers.

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Assessment of Limitations to Optimization of Guideline-Directed Medical Therapy in Heart Failure From the GUIDE-IT Trial: A Secondary Analysis of a Randomized Clinical Trial.

Fiuzat M, Ezekowitz J, Alemayehu W, Westerhout CM, Sbolli M, Cani D, Whellan DJ, Ahmad T, Adams K, Piña IL, Patel CB, Anstrom KJ, Cooper LS, Mark D, Leifer ES, Felker GM, Januzzi JL, O'Connor CM.
JAMA Cardiol . 2020;5:757-764.

Despite evidence that guideline-directed medical therapy (GDMT) improves outcomes in patients with heart failure and reduced ejection fraction (HFrEF), many patients are undertreated. Despite this fact, many patients in clinical practice are not treated with these agents or are treated with lower-than-recommended doses.

The Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment (GUIDE-IT) trial tested whether a strategy of using target concentrations of N-terminal pro–brain natriuretic peptide (NT-proBNP) to guide optimization of GDMT could improve outcomes in patients with HFrEF.

The authors conclude that despite a protocol-driven approach implemented by experienced HF cardiologists, many patients in the GUIDE-IT trial did not receive GDMT adjustments, particularly in the long term, even in those with known elevated NT-proBNP concentrations. These results suggest that GUIDE-IT may have failed to achieve the treatment benefit because of therapeutic inertia in clinical practice or that current GDMT goals may be unrealistic outside of trials. The opportunity to titrate GDMT remains in the care of patients with HFrEF, although some patients may be maximized before achieving GDMT.

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Long-term Outcomes of Complete Revascularization with Percutaneous Coronary Intervention in Acute Coronary Syndromes.

Bainey KR, Alemayehu W, Armstrong PW, Westerhout CM, Kaul P, Welsh RC.
JACC Cardiovasc Interv. 2020;13:1557-1567.

Controversy exists regarding the benefit of multi-vessel percutaneous coronary intervention (PCI) across the spectrum of acute coronary syndromes (ACS).

The authors, using a large population-based cohort of ACS patients with multi-vessel disease undergoing PCI, compared demographics, comorbidities, evidence-based medication use, and long-term clinical outcome in patients with complete revascularization and incomplete revascularization. They identified patient factors associated with complete revascularization and examined the relationship between the extent of incomplete revascularization and long-term outcome.

Their research concluded that results from this large angiographic disease-based registry of ACS patients with multi-vessel disease undergoing PCI, suggests complete revascularization occurs commonly and is associated with improved clinical outcome at 5 years including a 21% reduction in all-cause mortality. Until further randomized data becomes available, these data support complete revascularization following ACS.

The accompanying editorial by Mehta et al. can be read here.

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Association Between HbA1c Levels and Cardiovascular Outcomes in Patients With Type 2 Diabetes and Cardiovascular Disease: A Secondary Analysis of the TECOS Randomized Clinical Trial.

McAlister FA, Zheng Y, Westerhout CM, Buse JB, Standl E, McGuire DK, Van de Werf F, Green JB, Armstrong PW, Holman RR; TECOS Study Group.
Eur J Heart Fail . 2020. doi: 10.1002/ejhf.1958.

Heart failure (HF) is one of the most common complications of type 2 diabetes (T2D) due to the interplay of macrovascular and microvascular disease, the frequent coexistence of kidney disease, and the effect of insulin resistance on cardiac myocytes. Whether glycemic control is associated with cardiovascular outcomes in patients with T2D is unclear.

As the Trial Evaluating Cardiovascular Outcomes With Sitagliptin (TECOS) found no association between sitagliptin use and HF outcomes or all cardiovascular events, the authors designed this study to examine whether outcomes varied by baseline or average achieved HbA1c in TECOS participants.

The authors conclude that, given the U-shaped association between average achieved HbA1c exhibited during the TECOS trial and cardiovascular outcomes, targeting HbA1c of 7% may help optimize outcomes in patients with T2D and atherosclerotic vascular disease. Whether a similar target should be pursued for the prevention of HF in patients with T2D but without existing vascular disease is an important open question and future studies (ideally randomized trials) should compare different target HbA1c levels for the primary prevention of HF in patients with T2D.

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