Cause of Myocardial Injury Affects Mortality Risk in Patients Hospitalized With COVID-19

Since early in the COVID-19 pandemic, there has been evidence that the disease increases the risk of major adverse cardiovascular events, which in turn substantially increase the risk of death. Jeremy N. Ruskin, MD, founder and director emeritus of the Telemachus & Irene Demoulas Family Foundation Center for Cardiac Arrhythmias at the Corrigan Minehan Heart Center at Massachusetts General Hospital and Professor of Medicine at Harvard Medical School, Pegah Khaloo, MPH, research fellow in the center, and colleagues recently explored these relationships in one of the largest cohort studies conducted to date.

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In the International Journal of Cardiology, they report that elevation of high-sensitivity troponin T (hs-TnT) from any cause was a strong independent predictor of mortality in patients hospitalized with COVID-19, but the risk was substantially higher if the elevation had a primary cardiac etiology than if it was associated with a primary non-cardiac condition.

Methods

The researchers retrospectively studied 2,450 adults admitted to four hospitals in the Mass General Brigham network between March 15 and June 15, 2020, who had PCR-confirmed COVID-19. The median age was 64 years and 54% of patients were male.

88% of the cohort had hs-TnT measured with the fifth-generation assay at admission and throughout hospitalization. Transthoracic echocardiography was performed in 287 patients.

Troponin Elevation

Myocardial injury, defined as hs-TnT above the 99th percentile upper reference limit (9 ng/L for women, 14 ng/L for men), occurred in 1,401 patients (57%). 653 of them (47% of patients with elevated hs-TnT) had a primary cardiac etiology for the elevation:

• Acute congestive heart failure—23% of the entire cohort
• New-onset tachyarrhythmia/block—8.4%
• Non-diagnostic echocardiography abnormality—1.7%
• Cardiac arrest—0.7%
• Type 1 myocardial infarction (MI)—0.5%
• Type 2 MI—0.9%
• Probable myocarditis/pericarditis—0.5%
• Takotsubo syndrome—0.5%

748 patients had elevated hs-TnT in the absence of a primary cardiac etiology:

• Renal failure—41% of this subgroup
• Shock—14%
• Pulmonary embolism—3.2%
• Stroke—0.7%
• Critical illness as the only identifiable potential cause of the elevation—38%
• No identifiable cause—3.2%

Predictors of Mortality

335 patients (14%) died during hospitalization. Independent predictors of mortality were:

• Older age—OR, 1.06 per year
• Acute renal failure—OR, 1.9
• History of a cerebrovascular event—OR, 2.3
• History of atrioventricular block—OR, 2.5
• Shock—OR, 3.2
• New-onset stroke—OR, 3.6
• Elevated hs-TnT with a primary non-cardiac etiology—OR, 2.7
• Elevated hs-TnT with a primary cardiac etiology—OR, 4.6

In a multivariable analysis restricted to patients with elevated hs-TnT, mortality risk was significantly higher in patients with a primary cardiac cause for the elevation than in those with a non-cardiac cause (OR, 1.8; P<0.001). The mortality difference remained significant regardless of the hs-TnT blood level.

In an analysis restricted to patients who underwent echocardiography, predictors of mortality were:

• Older age—OR, 1.04 per year
• Acute kidney injury—OR, 2.6
• Right ventricular dysfunction—OR, 3.0
• Left ventricular wall motion abnormalities in >50% of segments measured—OR, 9.9

84% of patients who underwent echocardiography had normal left ventricle (LV) function, which presumably explains why global LV ejection fraction was not associated with mortality. Troponin T did not predict mortality in this subset, presumably because 88% of patients in this subcohort had elevated hs-TnT levels.

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