While long COVID holds many mysteries, researchers found clues to the heart symptoms common in these patients, which pointed to ongoing inflammation as the mediator.
In a cohort of 346 previously healthy patients with initially mild COVID-19, most seen for lingering symptoms a median of around 4 months later, structural heart disease and elevated biomarkers for cardiac injury or dysfunction were rare.
But there were plenty of signs of subclinical heart issues, reported Valentina O. Puntmann, MD, PhD, of University Hospital Frankfurt in Germany, and colleagues in Nature Medicine.
Compared with uninfected controls, the COVID patients had significantly higher diastolic blood pressure and more non-ischemic myocardial scar by late gadolinium enhancement, detectable pericardial effusion with no hemodynamic relevance, and pericardial enhancement by gadolinium contrast uptake in the pericardial layers (all P<0.001).
In addition, the 73% of COVID patients studied who had cardiac symptoms had higher mapping values denoting diffuse myocardial inflammation and more pericardial contrast agent accumulation on cardiac MR (CMR) imaging than asymptomatic individuals.
"What we see is relatively mild," Puntmann told MedPage Today. "These are patients that were previously normal."
The findings provided a window into a different group than often considered for cardiac problems from COVID-19, as patients with pre-existing heart problems were more likely to land in the hospital and to have severe disease and sequelae from that.
Puntmann's group has been studying people without prior heart issues to try to home in on the impact of COVID-19 itself, using research-level CMR imaging on patients recruited to their clinic via promotional materials disseminated through family practitioners, health authority centers, patient online groups, and websites.
While it's a select patient group that might not be representative of mild COVID-19 cases overall, these patients who seek out answers for their symptoms aren't that uncommon either, Puntmann noted.
Federal survey data suggest that 19% of U.S. adults who had COVID have had symptoms that lasted 3 or more months after infection. In the current study, follow-up scans at a median of around 11 months after COVID-19 diagnosis showed ongoing cardiac symptoms in 57% of the participants. Those persistently symptomatic patients had more pronounced diffuse myocardial edema than those who recovered or never had symptoms (native T2 37.9 vs 37.4 and 37.5 ms, P=0.04).
"Cardiac involvement is an important part of the long COVID presentation -- so the shortness in breath, the effort intolerance, tachycardia," Puntmann said in an interview.
Her group concluded that the cardiac symptoms they saw "were related to subclinical inflammatory cardiac involvement, which may, at least in part, explain the pathophysiological background of persistent cardiac symptoms. Notably, profound myocardial injury or structural heart disease is not prerequisite for the presence of symptoms defying the classical definitions of viral myocarditis."
One important clinical implication was pointed out by cardiologist and long COVID patient Alice A. Perlowski, MD, who tweeted: "This study illustrates how traditional biomarkers (in this case CRP, troponin, NT-proBNP) are likely NOT telling the whole story in #LongCovid. I hope all clinicians seeing these patients in their practices can take this key point away."
Among the 346 adults with COVID-19 (mean age 43.3, 52% women) assessed at a single center from April 2020 to October 2021 a median of 109 days after infection, the most common cardiac symptoms were exertional dyspnea (62%), palpitations (28%), atypical chest pain (27%), and syncope (3%).
"It is a problem understanding what is going on with a routine cardiac investigation, because it is very difficult to capture that is very abnormal," Puntmann said. "This is partially because of the pathophysiology behind it. ... Even if their function is impaired, it is not going to be so dramatic because they compensate for this through tachycardia and also very excited heart function. So we don't yet see them in the stage of decompensation."
The group plans to continue following these patients longer term to see what the potential clinical consequences might be, with concern as noted on the center's website that it "may herald a considerable burden of heart failure in a few years from now." The group is also initiating the placebo-controlled MYOFLAME-19 trial to test anti-inflammatory and renin-angiotensin system-targeted medications for this population.
Their study included only patients without previously known cardiac conditions, comorbidities, or abnormal lung function tests at the baseline assessment and who had not been hospitalized for acute COVID-19 at any point.
Another 95 of the clinics' patients with no prior COVID-19 and no known heart disease or comorbidities were used as a control group. While the researchers acknowledged that there may have been unrecognized differences compared with the COVID patients, they noted the similar distribution for age, sex, and cardiovascular risk factors.
Of the COVID patients with symptoms, these were mild or moderate for most (38% and 33%, respectively), and only nine (3%) had severe symptoms that limited the activities of daily life.
Factors that independently predicted cardiac symptoms that persisted from the baseline scan to the repeat scan at least 4 months later (median 329 days post diagnosis) were female gender and diffuse myocardial involvement on baseline imaging.
"Notably, as our study focused on a selected population of individuals with prior COVID illness, it does not inform on the prevalence of cardiac symptoms after COVID," Puntmann's group wrote. "However, it provides important insights into their spectrum and subsequent evolution."