We present, to our knowledge, the first cohort of COVID-19 patients with baseline, pre-infection echocardiographic characteristics and their relation to disease severity. Though there have been many investigations reporting TTE findings among COVID-19 patients, 12–15 these have largely been aimed at investigating the impact of COVID-19 on the heart vis-à-vis echocardiographic abnormalities among patients hospitalized with COVID-19. Although important by way of adding to our knowledge of the full gamut of organ involvement by this relatively novel virus, and hence aiding description of the full signature of COVID-19, our study was aimed at investigating a more “upstream” role of TTE in COVID-19 patients. In other words, instead of investigating the impact of COVID-19 on echocardiographic parameters, we aimed to investigate the converse, i.e., the impact of echocardiographic parameters/abnormalities on COVID-19 patients. The most important findings from our cohort include, 1) both clinical and TTE abnormalities were substantially more common in hospitalized versus non-hospitalized patients, i.e. in those with more than mild disease, 2) in general, LV structural abnormalities and pulmonary hypertension predicted risk of non-mild disease, while LV functional parameters did not, and most importantly, 3) after adjusting for medical co-morbidities and other echocardiographic abnormalities, LA enlargement was independently associated with worse than mild disease.
Moreover, we found that in general, clinical co-morbidities as well as most TTE parameters were not significantly different between patients with moderate versus severe disease. In other words, beyond a certain threshold of disease severity, clinical co-morbidities or TTE abnormalities did not seem to discriminate those with uneventful hospital course from those requiring ICU stay, mechanical ventilatory support or death from COVID-19. Obviously, our cohort likely represents a somewhat higher risk cohort than the general population, due to the fact that patients who undergo TTE are generally older and more likely to have CV risk factors. Indeed, the prevalence of these risk factors in our cohort was somewhat higher than reported in previous cohorts including all-comers with COVID-19.3,16,17 Hence, the uniformly high and somewhat similar prevalence of these co-morbidities among hospitalized patients in our cohort possibly masked differences that may be evident in a larger sample. It is worth noting here that previous cohorts have generally reported a higher attributable risk to multi-organ injury, degree of hypoxemia, presence of respiratory distress syndrome, and/or inflammatory markers compared to medical co-morbidities among hospitalized patients, somewhat in support of our findings.3,17,18 In other words, the predictive value of medical co-morbidities seems to decline as disease severity increases.
In addition to the findings of the present data, there has been an abundance of literature evaluating the role of echocardiography in refining risk of cardiovascular events and mortality.19 Among various echocardiographic parameters, LA enlargement, a marker of long-standing or severe LV volume and/or pressure overload, and a risk factor for atrial fibrillation, thrombus formation and cardioembolic disease, has been associated with adverse cardiovascular outcomes.20–23 LA enlargement has been found to be an independent predictor of fatal and non-fatal cardiovascular events regardless of the presence of LVH.24 Finally, LA diameter has been shown to independently predict all-cause mortality in both men and women.25 Thus, it is not surprising that we found LA enlargement to be an echocardiographic parameter predicting risk of non-mild COVID-19, even when adjusted for LVH, and indeed when adjusted for clinical risk factors. To reiterate, we did not find a statistically significant difference in prevalence of LA enlargement among hospitalized patients suffering severe disease, though the prevalence was numerically higher in the latter (Table 1, 55.9% vs 47.2%). This was likely due to the relatively small sample size, and certainly worth investigating in larger cohorts. Conversely, it remains somewhat impressive that even in a modest-sized cohort such as ours, LA diameter proved additive to traditional risk factors in predicting risk of hospitalization. Admittedly we were restricted to using LA diameter as the parameter to define LA enlargement, rather than the currently recommended LA volume, largely because the latter was not routinely reported in majority of TTEs in our cohort. This is obviously a major limitation, especially since LA enlargement (as defined by LA diameter) emerged as the only echocardiographic predictor of hospitalization. However, ample evidence exists regarding the prognostic value of LA diameter, and though now superseded by LA volume, remains a premier predictor of outcomes.19,21,26 We believe that even given this limitation, our findings still strongly support the fundamental hypothesis that LA enlargement predicts risk of hospitalization among COVID-19 patients.
There are some other important limitations to our findings. Firstly, our study is retrospective. Secondly, we had a relatively modest sample size. Thirdly, we did not have the time/resources to have all TTEs re-interpreted using a strictly standardized methodology. In other words, all TTEs parameters were extracted as originally interpreted at the time of the TTE, obviously raising the possibility of non-uniform methodology in performing and interpreting the TTE. However, all TTEs were performed in the same lab, and any heterogeneity that may exist in technique/interpretation should be randomly distributed across patient groups. To our way of thinking, this should in fact make our findings closer to the “real-world”. Moreover, our strategy to define mild versus moderate disease severity based on need for hospitalization may be criticized since different physicians have different thresholds to admit patients with COVID-19. However, we at SLUHN had a very uniform set of criteria to guide admission with COVID-19 given the sudden surge of patients early during the pandemic in neighboring New York city. Hence, we believe that inter-physician heterogeneity in deciding to admit patients was minimal. Finally, given that patients who have TTE at baseline are generally older and more likely to have suspected or known cardiovascular disease, our findings may not be fully applicable to the general population. Regardless, we found that in patients who do have a baseline TTE, the presence of LA enlargement should raise concern about the patient’s risk of hospitalization, and perhaps warrant closer outpatient follow up and/or monitoring. At the very least our findings are novel and add to the available data on a novel and unprecedented disease. Moreover, quantifying risk is invaluable in stratifying common illnesses with a heavy disease burden, such as the current context. Our findings suggest that in patients in whom a recent TTE is available, the presence of LA enlargement may help refine triage.