Clustering of clinical and echocardiographic phenotypes of covid-19 patients.

We sought to divide COVID-19 patients into distinct phenotypical subgroups using echocardiography and clinical markers to elucidate the pathogenesis of the disease and its heterogeneous cardiac involvement. A total of 506 consecutive patients hospitalized with COVID-19 infection underwent complete evaluation, including echocardiography, at admission. A k-prototypes algorithm applied to patients' clinical and imaging data at admission partitioned the patients into four phenotypical clusters: Clusters 0 and 1 were younger and healthier, 2 and 3 were older with worse cardiac indexes, and clusters 1 and 3 had a stronger inflammatory response. The clusters manifested very distinct survival patterns (C-index for the Cox proportional hazard model 0.77), with survival best for cluster 0, intermediate for 1-2 and worst for 3. Interestingly, cluster 1 showed a harsher disease course than cluster 2 but with similar survival. Clusters obtained with echocardiography were more predictive of mortality than clusters obtained without echocardiography. Additionally, several echocardiography variables (E' lat, E' sept, E/e average) showed high discriminative power among the clusters. The results suggested that older infected males have a higher chance to deteriorate than older infected females. In conclusion, COVID-19 manifests differently for distinctive clusters of patients. These clusters reflect different disease manifestations and prognoses. Although including echocardiography improved the predictive power, its marginal contribution over clustering using clinical parameters only does not justify the burden of echocardiography data collection.

The added predictive role of echocardiography in patients with mild or moderate Coronavirus Disease 2019.

AIMS: Recently, several therapeutic agents have decreased the progression to critical disease in patients with mild/moderate COVID-19. However, their use is limited to patients with ≥1 clinical risk factor. We aimed to evaluate echocardiographic features that may aid in risk stratification for patients with mild/moderate COVID-19. METHODS: 278 consecutive patients with mild/moderate COVID-19 underwent prospective clinical and echocardiographic examination, ≤7 days of symptoms, as part of a predefined protocol. Analysis to identify echocardiographic predictors of outcome was performed. RESULTS: In the multivariable risk model, E/e', TAPSE, and pulmonary acceleration time (PAT) were associated with the composite outcome (p = 0.01, 0.005, 0.05, respectively). Stepwise analyses showed that the addition of echocardiography on top of having ≥1 clinical risk factor and even using each parameter separately improved the prediction of outcomes. If patients were re-categorized as high risk only if having both ≥1 clinical and ≥ 1 echocardiography risk parameter (E/e' > 8, TAPSE<1.8 cm, PAT<90 msec), or even one echo parameter separately, then specificity, positive predictive value, and accuracy improved. If patients were re-classified as high risk if having either ≥1 clinical risk factor or ≥ 1 high-risk echocardiography parameter, all five individuals who were missed by the ≥1 risk factor "rule", were correctly diagnosed as high risk. Similar analyses, including only patients with mild disease, showed that the addition of TAPSE improved the prediction of outcomes. CONCLUSIONS: In patients with mild/moderate COVID-19, a very limited echocardiographic exam is sufficient for improved outcome prediction, and may improve resource allocation for new anti-COVID-19 agents. TRANSLATIONAL ASPECT OF THE WORK: We show that among patients with mild/moderate COVID-19, several easily obtained echocardiographic findings are strongly correlated with mortality or progression to the need for invasive/non-invasive mechanical ventilation, even when adjusted for the presence or absence of ≥1 clinical risk factor. Furthermore, even a limited echocardiographic exam is sufficient to develop a strategy of risk stratification. We believe that our data have important implications for the clinicians involved in the acute treatment of patients with COVID-19.

The added predictive role of echocardiography in patients with mild or moderate Coronavirus Disease 2019

Aims Recently, several therapeutic agents have decreased the progression to critical disease in patients with mild/moderate COVID-19. However, their use is limited to patients with ≥1 clinical risk factor. We aimed to evaluate echocardiographic features that may aid in risk stratification for patients with mild/moderate COVID-19. Methods 278 consecutive patients with mild/moderate COVID-19 underwent prospective clinical and echocardiographic examination, ≤7 days of symptoms, as part of a predefined protocol. Analysis to identify echocardiographic predictors of outcome was performed. Results In the multivariable risk model, E/e′, TAPSE, and pulmonary acceleration time (PAT) were associated with the composite outcome (p = 0.01, 0.005, 0.05, respectively). Stepwise analyses showed that the addition of echocardiography on top of having ≥1 clinical risk factor and even using each parameter separately improved the prediction of outcomes. If patients were re-categorized as high risk only if having both ≥1 clinical and ≥ 1 echocardiography risk parameter (E/e′ > 8, TAPSE<1.8 cm, PAT<90 msec), or even one echo parameter separately, then specificity, positive predictive value, and accuracy improved. If patients were re-classified as high risk if having either ≥1 clinical risk factor or ≥ 1 high-risk echocardiography parameter, all five individuals who were missed by the ≥1 risk factor “rule”, were correctly diagnosed as high risk. Similar analyses, including only patients with mild disease, showed that the addition of TAPSE improved the prediction of outcomes. Conclusions In patients with mild/moderate COVID-19, a very limited echocardiographic exam is sufficient for improved outcome prediction, and may improve resource allocation for new anti-COVID-19 agents. Translational aspect of the work We show that among patients with mild/moderate COVID-19, several easily obtained echocardiographic findings are strongly correlated with mortality or progression to the need for invasive/non-invasive mechanical ventilation, even when adjusted for the presence or absence of ≥1 clinical risk factor. Furthermore, even a limited echocardiographic exam is sufficient to develop a strategy of risk stratification. We believe that our data have important implications for the clinicians involved in the acute treatment of patients with COVID-19.

Pericardial Involvement in Patients Hospitalized With COVID-19: Prevalence, Associates, and Clinical Implications.

Background The scope of pericardial involvement in COVID-19 infection is unknown. We aimed to evaluate the prevalence, associates, and clinical impact of pericardial involvement in hospitalized patients with COVID-19. Methods and Results Consecutive patients with COVID-19 underwent clinical and echocardiographic examination, irrespective of clinical indication, within 48 hours as part of a prospective predefined protocol. Protocol included clinical symptoms and signs suggestive of pericarditis, calculation of modified early warning score, ECG and echocardiographic assessment for pericardial effusion, left and right ventricular systolic and diastolic function, and hemodynamics. We identified predictors of mortality and assessed the adjunctive value of pericardial effusion on top of clinical and echocardiographic parameters. The study included 530 patients. Pericardial effusion was found in 75 (14%), but only 17 patients (3.2%) fulfilled the criteria for acute pericarditis. Pericardial effusion was independently associated with modified early warning score, brain natriuretic peptide, and right ventricular function. It was associated with excess mortality (hazard ratio [HR], 2.44; P=0.0005) in nonadjusted analysis. In multivariate analysis adjusted for modified early warning score and echocardiographic and hemodynamic parameters, it was marginally associated with mortality (HR, 1.86; P=0.06) and improvement in the model fit (P=0.07). Combined assessment for pericardial effusion with modified early warning score, left ventricular ejection fraction, and tricuspid annular plane systolic excursion was an independent predictor of outcome (HR, 1.86; P=0.02) and improved model fit (P=0.02). Conclusions In hospitalized patients with COVID-19, pericardial effusion is prevalent, but rarely attributable to acute pericarditis. It is associated with myocardial dysfunction and mortality. A limited echocardiographic examination, including left ventricular ejection fraction, tricuspid annular plane systolic excursion, and assessment for pericardial effusion, can contribute to outcome prediction.

Cardiorespiratory Abnormalities in Patients Recovering from Coronavirus Disease 2019.

BACKGROUND: A large number of patients around the world are recovering from coronavirus disease 2019 (COVID-19); many of them report persistence of symptoms. The aim of this study was to test pulmonary, cardiovascular, and peripheral responses to exercise in patients recovering from COVID-19. METHODS: Patients who recovered from COVID-19 were prospectively evaluated using a combined anatomic and functional assessment. All patients underwent clinical examination, laboratory tests, and combined stress echocardiography and cardiopulmonary exercise testing. Left ventricular volumes, ejection fraction, stroke volume, heart rate, E/e' ratio, right ventricular function, oxygen consumption (Vo2), lung volumes, ventilatory efficiency, oxygen saturation, and muscle oxygen extraction were measured in all effort stages and compared with values in historical control subjects. RESULTS: A total of 71 patients were assessed 90.6 ± 26 days after the onset of COVID-19 symptoms. Only 23 (33%) were asymptomatic. The most common symptoms were fatigue (34%), muscle weakness or pain (27%), and dyspnea (22%). Vo2 was lower among post-COVID-19 patients compared with control subjects (P = .03, group-by-time interaction P = .007). Reduction in peak Vo2 was due to a combination of chronotropic incompetence (75% of post-COVID-19 patients vs 8% of control subjects, P < .0001) and an insufficient increase in stroke volume during exercise (P = .0007, group-by-time interaction P = .03). Stroke volume limitation was mostly explained by diminished increase in left ventricular end-diastolic volume (P = .10, group-by-time interaction P = .03) and insufficient increase in ejection fraction (P = .01, group-by-time interaction P = .01). Post-COVID-19 patients had higher peripheral oxygen extraction (P = .004) and did not have significantly different respiratory and gas exchange parameters compared with control subjects. CONCLUSIONS: Patients recovering from COVID-19 have symptoms associated with objective reduction in peak Vo2. The mechanism of this reduction is complex and mainly involves a combination of attenuated heart rate and stroke volume reserve.

Risk prediction in patients with COVID-19 based on haemodynamic assessment of left and right ventricular function.

AIMS: Cardiovascular involvement is common in COVID-19. We sought to describe the haemodynamic profiles of hospitalized COVID-19 patients and determine their association with mortality. METHODS AND RESULTS: Consecutive hospitalized patients diagnosed with COVID-19 infection underwent clinical evaluation using the Modified Early Warning Score (MEWS) and a full non-invasive echocardiographic haemodynamic evaluation, irrespective of clinical indication, as part of a prospective predefined protocol. Patients were stratified based on filling pressure and output into four groups. Multivariable Cox-Hazard analyses determined the association between haemodynamic parameters with mortality. Among 531 consecutive patients, 44% of patients had normal left ventricular (LV) and right ventricular (RV) haemodynamic status. In contrast to LV haemodynamic parameters, RV parameters worsened with higher MEWS stage. While RV parameters did not have incremental risk prediction value above MEWS, LV stroke volume index, E/e' ratio, and LV stroke work index were all independent predictors of outcome, particularly in severe disease. Patients with LV or RV with high filling pressure and low output had the worse outcome, and patients with normal haemodynamics had the best (P < 0.0001). CONCLUSION: In hospitalized patients with COVID-19, almost half have normal left and right haemodynamics at presentation. RV but not LV haemodynamics are related to easily obtainable clinical parameters. LV but not RV haemodynamics are independent predictors of mortality, mostly in patients with severe disease.

COVID-19, a tale of two peaks: patients' characteristics, treatments, and clinical outcomes.

Coronavirus 2019 disease (COVID-19) continues to challenge healthcare systems globally as many countries are currently experiencing an increase in the morbidity and mortality. Compare baseline characteristics, clinical presentation, treatments, and clinical outcomes of patients admitted during the second peak to those admitted during the first peak. Retrospective analysis of 258 COVID-19 patients consecutively admitted to the Tel Aviv Medical Center, of which, 131 during the first peak (March 21-May 30, 2020) and 127 during the second peak (May 31-July 16, 2020). First and second peak patients did not differ in baseline characteristics and clinical presentation at admission. Treatment with dexamethasone, full-dose anticoagulation, tocilizumab, remdesivir, and convalescent plasma transfusion were significantly more frequent during the second peak, as well as regimens combining 3-4 COVID-19-directed drugs. Compared to the first peak, 30-day mortality and invasive mechanical ventilation rates as well as adjusted risk were significantly lower during the second peak (10.2%, vs 19.8% vs p = 0.028, adjusted HR 0.39, 95% CI 0.19-0.79, p = 0.009 and 8.8% vs 19.3%, p = 0.002, adjusted HR 0.29, 95% CI 0.13-0.64, p = 0.002; respectively). Rates of 30-day mortality and invasive mechanical ventilation, as well as adjusted risks, were lower in the second peak of the COVID-19 pandemic among hospitalized patients. The change in treatment strategy and the experienced gained during the first peak may have contributed to the improved outcomes.

The Predictive Role of Combined Cardiac and Lung Ultrasound in Coronavirus Disease 2019.

BACKGROUND: The aim of this study was to evaluate sonographic features that may aid in risk stratification and to propose a focused cardiac and lung ultrasound (LUS) algorithm in patients with coronavirus disease 2019. METHODS: Two hundred consecutive hospitalized patients with coronavirus disease 2019 underwent comprehensive clinical and echocardiographic examination, as well as LUS, irrespective of clinical indication, within 24 hours of admission as part of a prospective predefined protocol. Assessment included calculation of the modified early warning score (MEWS), left ventricular systolic and diastolic function, hemodynamic and right ventricular assessment, and a calculated LUS score. Outcome analysis was performed to identify echocardiographic and LUS predictors of mortality or the composite event of mortality or need for invasive mechanical ventilation and to assess their adjunctive value on top of clinical parameters and MEWS. RESULTS: A simplified echocardiographic risk score composed of left ventricular ejection fraction < 50% combined with tricuspid annular plane systolic excursion < 18 mm was associated with mortality (P = .0002) and with the composite event (P = .0001). Stepwise analyses evaluating echocardiographic and LUS parameters on top of existing clinical risk scores showed that addition of tricuspid annular plane systolic excursion and stroke volume index improved prediction of mortality when added to clinical variables but not when added to MEWS. Once echocardiography was added, and patients were recategorized as high risk only if having both high-risk MEWS and high-risk cardiac features, specificity increased from 63% to 87%, positive predictive value from 28% to 48%, and accuracy from 66% to 85%. Although LUS was not associated with incremental risk prediction for mortality above clinical and echocardiographic criteria, it improved prediction of need for invasive mechanical ventilation. CONCLUSIONS: In hospitalized patients with coronavirus disease 2019, a very limited echocardiographic examination is sufficient for outcome prediction. The addition of echocardiography in patients with high-risk MEWS decreases the rate of falsely identifying patients as high risk to die and may improve resource allocation in case of high patient load.

Correction to: Lung ultrasound predicts clinical course and outcomes in COVID-19 patients.

The original article can be found online.

Lung ultrasound predicts clinical course and outcomes in COVID-19 patients.

PURPOSE: Information regarding the use of lung ultrasound (LUS) in patients with Coronavirus disease 2019 (COVID-19) is quickly accumulating, but its use for risk stratification and outcome prediction has yet to be described. We performed the first systematic and comprehensive LUS evaluation of consecutive patients hospitalized with COVID-19 infection, in order to describe LUS findings and their association with clinical course and outcome. METHODS: Between 21/03/2020 and 04/05/2020, 120 consecutive patients admitted to the Tel Aviv Medical Center due to COVID-19, underwent complete LUS within 24 h of admission. A second exam was performed in case of clinical deterioration. LUS score of 0 (best)-36 (worst) was assigned to each patient. LUS findings were compared with clinical data. RESULTS: The median baseline total LUS score was 15, IQR [7-20]. Baseline LUS score was 0-18 in 80 (67%) patients, and 19-36 in 40 (33%) patients. The majority had patchy pleural thickening (n = 100; 83%), or patchy subpleural consolidations (n = 93; 78%) in at least one zone. The prevalence of pleural thickening, subpleural consolidations and the total LUS score were all correlated with severity of illness on admission. Clinical deterioration was associated with increased follow-up LUS scores (p = 0.0009), mostly due to loss of aeration in anterior lung segments. The optimal cutoff point for LUS score was 18 (sensitivity = 62%, specificity = 74%). Both mortality and need for invasive mechanical ventilation were increased with baseline LUS score > 18 compared to baseline LUS score 0-18. Unadjusted hazard ratio of death for LUS score was 1.08 per point [1.02-1.16], p = 0.008; Unadjusted hazard ratio of the composite endpoint (death or need for invasive mechanical ventilation) for LUS score was 1.12 per point [1.05-1.2], p = 0.0008. CONCLUSION: Hospitalized patients with COVID-19, at all clinical grades, present with pathological LUS findings. Baseline LUS score strongly correlates with the eventual need for invasive mechanical ventilation and is a strong predictor of mortality. Routine use of LUS may guide patients' management strategies, as well as resource allocation in case of surge capacity.