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.

Background and Objectives We aimed to evaluate sonographic features that may aid in risk stratification and propose a focused cardiac and lung ultrasound (LUS) algorithm in patients with COVID-19 Methods Two hundred consecutive hospitalized patients with COVID-19 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 (LV) systolic and diastolic function, hemodynamic and right ventricular (RV) assessment and a calculated LUS score. We performed outcome analysis 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 comprised of LV ejection fraction< 50% combined with TAPSE< 18 mm, was associated with mortality (p=0.0002) and with the composite event (p=0.0001). Stepwise analyses evaluating echocardiographic and LUS parameters on top of existing clinical risk scores showed that addition of TAPSE and SVI improved prediction of mortality when added to clinical variables but not when added to MEWS. Once echocardiography was added, and patients re-categorized as high risk only if having both high risk MEWS, and high-risk cardiac features, the specificity increased from 63% to 87%, positive predictive value from 28% to 48% and accuracy improved 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 COVID-19, a very limited echocardiographic exam is sufficient for outcome prediction. The addition of echocardiography in patients with high risk MEWS score decreases the rate of falsely identifying patients as high risk to die, and may improve resource allocation in case of high patient load.background

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.

BACKGROUND The list of medications linked to drug-induced long QT syndrome (LQTS) is diverse. It is possible that food products too have QT-prolonging potential.OBJECTIVE We tested the effects of grapefruit juice on the QT interval with the methodology used by the pharmaceutical industry to test new drugs. METHODSThis was an open-label, randomized, crossover study with blinded outcome evaluation, a thorough QT study of grapefruit juice performed according to the Guidelines for the Clinical Evaluation of QT/QTc for Non-antiarrhythmic Drugs. Thirty healthy volunteers and 10 patients with congenital LQTS were studied. Healthy volunteers drank 2 L of grapefruit juice (in divided doses), or received 400 mg oral moxifloxacin, in a randomized crossover study. Patients with LQTS were tested with only grapefruit. Repeated baseline, off-drug, and on-drug (grapefruit or moxifloxacin) electrocardiograms were scanned and coded. QT measurements were done with electronic calipers. RESULTSIn comparison to off-drug electrocardiograms, grapefruit juice led to significant rate-corrected QT (QTc) prolongation. The absolute net QTc prolongation from grapefruit was 14.0 ms (95% confidence interval 6.2-21.7 ms; P , .001). The QT-prolonging effects of grapefruit in healthy volunteers were comparable with those of moxifloxacin. The QT-prolonging effects of grapefruit juice were greater in female patients and particularly marked in patients with LQTS (net QTc prolongation 21.8 ms; 95% confidence interval 3.4-35.3 ms; P 5 .034).CONCLUSION Grapefruit juice, at doses tested, prolongs the QT interval. The effect is significant in healthy volunteers, greater in female patients, and more so in patients with LQTS.

Objective Subclinical myocardial dysfunction has been reported to occur early in systemic lupus erythematous (SLE). The study aim was to search for biomarkers of subclinical myocardial dysfunction which may correlate with disease activity in SLE patients. Methods This is a prospective, controlled, cross-sectional study of 57 consecutive patients with SLE and 18 controls. Serum samples were obtained to determine serum soluble ST2 (sST2), CXCL-10 and high-sensitivity troponin (hs-troponin) levels. All participants underwent an echocardiographic tissue Doppler study. Results sST2, CXCL-10 and hs-troponin levels were higher in patients with higher SLE disease activity (SLEDAI). sST2 and CXCL-10 levels were higher in patients with more disease damage as measured by the SLE damage index. Measures of diastolic dysfunction, as assessed by echocardiographic tissue Doppler negatively correlated with log CXCL-10: including E/A; E/e′lateral and E/e′septal, while E/e′ positively correlated with CXCL-10. Diastolic dysfunction parameters also correlated with log sST2 levels, a negative correlation was seen with E/e′lateral and a positive correlation was seen with E/e′. Systolic dysfunction parameters positively correlated with hs-troponin: LVED, LVES, IVS, LVMASS and LVMASS index. In a multivariate analysis, sST2 and CXCL-10 were found to be significantly different in SLE vs. healthy controls, independent of each other and independent of cardiovascular risk factors. Conclusions Soluble ST2 and CXCL-10 are markers of disease activity and accrued damage in SLE and may serve as sensitive biomarkers for detection of subclinical diastolic dysfunction, independent of traditional cardiovascular risk factors.

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Aims Most patients with significant (defined as ≥ moderate) tricuspid regurgitation (TR) are treated conservatively. Individual mortality rates are markedly variable. We developed a risk score based on comprehensive clinical and echocardiographic evaluation, predicting mortality on an individual patient level. Methods and results The cohort included 1,701 consecutive patients with significant TR, half with isolated TR, admitted to a single hospital, treated conservatively. We derived a scoring system predicting one-year mortality and validated it using k-fold cross validation and with external validation on another cohort of 5,141 patients. Score utility was compared to matched patients without significant TR. One-year mortality rate was 31.3%. The risk score ranged 0-17 points and included 11 parameters: age (0-3), body-mass-index ≤ 25 (0-1), history of liver disease (0-2), history of chronic lung disease (0-2), estimated-glomerular-filtration-rate (0-5), hemoglobin (0-2), left-ventricular-ejection-fraction (0-1), right-ventricular dysfunction (0-1), right-atrial-pressure (0-2), stroke-volume-index (SVI) (0-1) and left ventricular end-diastolic-diameter (0-1). One-year mortality rates increased from 0% to 100%, as the score increased up to ≥16. Areas under the receiver operating curves were 0.78, 0.70 and 0.73, for the original, external validation and external validation with SVI measured cohorts. The score remained valid in subpopulations of patients with quantified RV function, quantified TR and isolated TR. Significant TR compared to no TR, affected one-year mortality stronger with higher scores, with a significantly positive interaction term. Conclusion We suggest a robust risk score for inpatients with significant TR, assisting risk stratification and decision making. Our findings underscore the burden of TR providing benchmarks for clinical trial design.

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