Two studies raise new concerns about long-term cardiac injury

Two newly published studies raise concerns about lasting myocardial injury and heart failure related to Covid-19 infection.

An analysis of autopsy data from 39 consecutive patients in Germany with a diagnosis of SARS-CoV-2 prior to death showed viral positivity in cardiac tissue from 24 of the cases, with viral load greater than 1,000 copies identified in 16.

In a related study involving German patients who had recently recovered from Covid-19, magnetic resonance imaging (MRI) revealed cardiac tissue involvement in 78% and ongoing myocardial inflammation in 60%.

Both studies were published online July 27 in JAMA Cardiology.

In an editorial, JAMA editors Clyde Yancy, MD, of Northwestern University, Chicago and Gregg Fonarow, MD, of the University of California, Los Angeles, wrote that cardiomyopathy and heart failure related to Covid-19 “may potentially evolve as the natural history of this infection becomes clearer.”

“We wish not to generate additional anxiety but rather to incite other investigators to carefully examine existing and prospectively collected new data in other populations to confirm or refute these findings,” they wrote.

“Given the pressing burden of the ongoing Covid-19 crisis, as well as the initiation of longitudinal care models for those recovering from Covid-19, the concerns we are raising are not theoretical but instead practical and require our due diligence to study and prepare for what may be another dimension of the Covid-19 crisis.”

Myocardial dysfunction and elevated troponin levels have been described in the setting of Covid-19, with one study showing myocardial dysfunction on echocardiography in up to 70% of hospitalized patients.

In the autopsy study, researcher Diana Lindner, PhD, of the University Heart and Vascular Center, Hamburg, Germany, and colleagues, sought to explore “whether SARS-CoV-2 can be documented and replicates within the heart and whether this is associated with mononuclear cell infiltration or induces cytokine expression” in Covid-19 patients who died without clinically overt myocardiosis.”

The study involved consecutive autopsy data from people with confirmed SARS-CoV-2 infection autopsied at a single center in Hamburg, Germany between April 8 and April 18.

Cardiac tissue was collected with median postmortem intervals of 3.0 (IQR, 2.0-4.3) days. Two tissue specimens were taken from the left ventricle and either snap frozen in liquid nitrogen or fixed in formalin for later analysis.

The main outcome measures were incidence of SARS-CoV-2 positivity in cardiac tissue as well as CD3+, CD45+, and CD68+ cells in the myocardium and gene expression of TNFα, IFNγ, chemokine ligand 5, as well as IL-6, -8, and -18.

The median age of the 39 deceased patients was 85 (78-89) years, and 23 (59%) were female. SARS-CoV-2 could be documented in cardiac tissue from 24 of 39 patients (61.5%), and viral load above 1,000 copies per μg RNA could be documented in 16 of 39 patients (41.0%).

“A cytokine response panel consisting of 6 pro-inflammatory genes was increased in those 16 patients compared with 15 patients without any SARS-CoV-2 in the heart,” Lindner and colleagues wrote, adding that comparison of 15 patients without cardiac infection with 16 patients with more than 1,000 copies revealed no inflammatory cell infiltrates or differences in leukocyte numbers per high power field.

“Overt fulminant myocarditis has been reported in isolated patients with SARS-CoV-2 infection. However, the current data indicate that the presence of SARS-CoV-2 in cardiac tissue does not necessarily cause an inflammatory reaction consistent with clinical myocarditis,” they wrote.

In the related study, researchers sought to examine the presence of myocardial injury in unselected patients who had recently recovered from Covid-19.

The observational study involved 100 such patients identified from a University hospital registry in Frankfurt, Germany between April and June of this year.

Demographic characteristics, cardiac blood markers and cardiovascular MRI were all obtained, and comparisons were made between the 100 recovered Covid-19 patients and age – and sex-matched controls of healthy volunteers (n=50) and risk factor-matched patients (n=57).

Sixty-seven (67%) of the Covid-19 patients recovered at home, while 33 (33%) required hospitalization.

At the time of cardiovascular MRI, high-sensitivity troponin T (hsTnT) was detectable (3 pg/mL or greater) in 71 patients recently recovered from Covid-19 (71%) and significantly elevated (13.9 pg/mL or greater) in 5 patients (5%).

Compared with healthy controls and risk factor–matched controls, patients recently recovered from Covid-19 had lower left ventricular ejection fraction, higher left ventricle volumes, higher left ventricle mass, and raised native T1 and T2.

Among the other main findings:

  • A total of 78 patients recently recovered from Covid-19 (78%) had abnormal cardiac MRI findings, including raised myocardial native T1 (n = 73), raised myocardial native T2 (n = 60), myocardial late gadolinium enhancement (n = 32), and pericardial enhancement (n = 22).
  • A small but significant difference was seen between patients who recovered at home versus in the hospital for native T1 mapping (median [IQR], 1122 [1113-1132] ms versus 1143 [1131-1156] ms; P=0.02) but not for native T2 mapping or hsTnT levels.
  • These measures were not correlated with time from Covid-19 diagnosis (native T1: r = 0.07; P= 0.47; native T2: r = 0.14; P=0.15; hsTnT: r = −0.07; P=.50).
  • High-sensitivity troponin T was significantly correlated with native T1 mapping (r = 0.35; P<0.001) and native T2 mapping (r = 0.22; P=.03).

The researchers concluded that the findings “indicate the need for ongoing investigation of the long-term cardiovascular consequences of Covid-19.”

Yancy and Fonarow noted that these investigations are urgently needed to know if long-term cardiovascular injury is a common consequence of Covid-19.

“We hope these findings represent that of a select cohort of patients,” they wrote. “Yet, if this high rate of risk is confirmed, the pathologic basis for progressive left-ventricular dysfunction is validated, and especially if longitudinal assessment reveals new-onset heart failure in he recovery phase of Covid-19, then the crisis of Covid-19 will not abate but will instead shift to a new de novo incidence of heart failure and other chronic cardiovascular complications.”

  1. An analysis of autopsy data from 39 consecutive patients in Germany with a diagnosis of SARS-CoV-2 prior to death showed viral positivity in cardiac tissue from 24 of the cases, with viral load greater than 1,000 copies identified in 16.
  2. In patients who had recovered from Covid-19, MRI revealed cardiac tissue involvement in 78% and ongoing myocardial inflammation in 60%.

Salynn Boyles, Contributing Writer, BreakingMED™

Grant support for the study by Puntmann and colleagues was provided by the German Ministry of Education and Research via the German Centrefor Cardiovascular Research partner site Rhein Main, Deutsche Herzstifung eV, Bayer and the Cardio-Pulmonary Institute.

Researcher Valentina Puntmann reported no relevant conflicts of interest. Principal investigator Eike Nagel reported receiving grants from Bayer, the German Ministry for Education and Research, Deutsche Herzstiftung eV, Neosoft Technologies and Cardio-Pulmonary Institute and personal fees from Bayer.

Grant support for the study by Lindner and colleagues was provided by Deutsche Herzstiftlung and the German Center of Cardiovascular Research.

Lead researcher Diana Lindner reported no relevant conflicts. Principal investigator Dirk Westermann reported receiving personal fees from AstraZeneca, Bayer, Novartis and Medtronic outside the submitted work.

Editorial co-author Gregg C. Fonarow reported receiving personal fees from Abbott Laboratories, Amgen, AstraZeneca, Bayer, CHF Solutions, Edwards Lifesciences, Janssen, Medtronic, Merck and Novartis outside the submitted work.

 

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