Exercise limitation in hypertrophic cardiomyopathy: combined stress echocardiography and cardiopulmonary exercise test.

AIMS: The study aims to investigate exercise-limiting factors in hypertrophic cardiomyopathy (HCM) using combined stress echocardiography and cardiopulmonary exercise test. METHODS AND RESULTS: A symptom-limited ramp bicycle exercise test was performed in the semi-supine position on a tilting dedicated ergometer. Echocardiographic images were obtained concurrently with gas exchange measurements along predefined stages of exercise. Oxygen extraction was calculated using the Fick equation at each activity level. Thirty-six HCM patients (mean age 67 ± 6 years, 72% men, 18 obstructive HCM) were compared with age and sex-matched 29 controls. At rest, compared with controls, E/E' ratio (6.26 ± 2.3 vs. 14 ± 2.5, P < 0.001) and systolic pulmonary artery pressures (SPAP) (22.6 ± 3.4 vs. 34 ± 6.2 mmHg, P = 0.023) were increased. Along with the stages of exercise (unloaded; anaerobic threshold; peak), diastolic function worsened (E/e' 8.9 ± 2.6 vs. 13.8 ± 3.6 P = 0.011; 9.4 ± 2.3 vs. 18.6 ± 3.3 P = 0.001; 8.7 ± 1.9 vs. 21.5 ± 4, P < 0.001), SPAP increased (23 ± 2.7 vs. 33 ± 4.4, P = 0.013; 26 ± 3.2 vs. 40 ± 2.9, P < 0.001; 26 ± 3.5 vs. 45 ± 7 mmHg, P < 0.001), and oxygen consumption (6.6 ± 1.7 vs. 6.8 ± 1.6, P = 0.86; 18.1 ± 2.2 vs. 14.6 ± 1.5, P = 0.008; 20.3 ± 3 vs. 15.1 ± 2.1 mL/kg/min, P = 0.01) was reduced. Oxygen pulse was blunted (6.3 ± 1.8 vs. 6.2 ± 1.9, P = 0.79; 10 ± 2.1 vs. 8.8 ± 1.6, P = 0.063; 12.2 ± 2 vs. 8.2 ± 2.3 mL/beat, P = 0.002) due to an insufficient increase in both stroke volume (92.3 ± 17 vs. 77.3 ± 14.5 P = 0.021; 101 ± 19.1 vs. 87.3 ± 15.7 P = 0.06; 96.5 ± 12.2 vs. 83.6 ± 16.1 mL, P = 0.034) and oxygen extraction (0.07 ± 0.03 vs. 0.07 ± 0.02, P = 0.47; 0.13 ± 0.02 vs. 0.10 ± 0.03, P = 0.013; 0.13 ± 0.03 vs. 0.11 ± 0.03, P = 0.03). Diastolic dysfunction, elevated SPAP, and the presence of atrial fibrillation were associated with reduced exercise capacity. CONCLUSIONS: Both central and peripheral cardiovascular limitations are involved in exercise intolerance in HCM. Diastolic dysfunction seems to be the main driver for this limitation.

Prognostic impact of combined non-severe aortic stenosis and mitral regurgitation on clinical outcomes: a single-centre retrospective study.

OBJECTIVES: Though the concomitant occurrence of non-severe aortic stenosis (AS) and mitral regurgitation (MR) is highly prevalent, there are limited data to guide clinical decision-making in this condition. Here, we attempt to determine an aortic valve area (AVA) cut-off value associated with worse clinical outcomes in patients with combined non-severe AS and MR. METHODS: Single-centre, retrospective analysis of consecutive patients who underwent echocardiography examination between 2010 and 2021 with evidence of combined non-severe AS and MR. We excluded patients with ≥moderate aortic valve regurgitation or mitral stenosis, as well as patients who underwent any aortic or mitral intervention either prior or following our assessment (n=372). RESULTS: The final cohort consisted of 2933 patients with non-severe AS, 506 of them with >mild MR. Patients with both pathologies had lower cardiac output and worse diastolic function.Patients with an AVA ≤1.35 cm² in the presence of >mild MR had the highest rates of heart failure (HF) hospitalisations (HR 3.1, IQR 2.4-4, p<0.001) or mortality (HR 2, IQR 1.8-2.4, p<0.001), which remained significant after adjusting for clinical and echocardiographic parameters. CONCLUSION: Patients with combined non-severe AS and MR have a higher rate of HF hospitalisations and mortality. An AVA≤1.35 cm² in the presence of >mild MR is associated with worse clinical outcomes.

Implications of Indeterminate and Determined Etiologies Leading to Small Left Atria.

BACKGROUND: Small left atria (LA) is associated with an increased risk of mortality. OBJECTIVES: To determine whether the attributed risk of mortality is influenced by the underlying etiologies leading to decreased volumes. METHODS: We retrospectively evaluated patients with an available LA volume index (LAVI) as measured by echocardiography who came to our institution between 2011 and 2016. Individuals with small LA (LAVI < 16 ml/m2) were included and divided according to the etiology of the small LA (determined or indeterminate) and investigated according to the specific etiology. RESULTS: The cohort consisted of 288 patients with a mean age of 56 ± 18 years. An etiology for small LA was determined in 84% (n=242). The 1-year mortality rate of the entire cohort was 20.5%. Patients with indeterminate etiology (n=46) demonstrated a lower mortality rate compared with determined etiologies (8.7% vs. 22.7%, P = 0.031). However, following propensity score adjustments for baseline characteristics, there was no significant difference between the groups (P = 0.149). The only specific etiology independently associated with 1-year mortality was the presence of space occupying lesions (odds ratio 3.26, 95% confidence interval 1.02-10.39, P = 0.045). CONCLUSIONS: Small LA serve as a marker for negative outcomes, and even in cases of undetected etiology, the prognosis remains poor. The presence of small LA should alert the physician to a high risk of mortality, regardless of the underlying disease.

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.

Advances, Challenges, and Progress in Cardiac Rehabilitation in Chronic CVD Management.

PURPOSE OF REVIEW: To review the benefits, challenges, and advances in cardiac rehabilitation (CR) in the management of cardiovascular disease (CVD). RECENT FINDINGS: Novel strategies of delivering CR are being studied that use remote technologies to link patients with CR professionals. These strategies used alone or in tandem with center-based, face-to-face strategies appear to have shorter-term effectiveness, but additional work is needed to assess the longer-term impact. Cardiac rehabilitation improves patient outcomes, but only a minority of eligible individuals participate. Solutions exist to help bridge the barriers to CR participation, including systematic solutions, such as automatic CR referral of eligible patients. Efforts are underway to improve participation, improve the effectiveness of CR therapies, and enhance the reach of CR into new patient groups. Future work in the field is focused on opportunities to advance the science, practice, and policies that will shape and improve the delivery and impact of CR services.

Risk stratification according to diastolic function indices in heart failure patients with mildly reduced or reduced ejection fraction.

Aims: The aim of the study is to evaluate the risk of all-cause mortality or heart failure hospitalizations in ambulatory patients with heart failure with reduced and mildly reduced ejection fraction (HFrEF or HFmrEF) according to diastolic function indices. Diastolic dysfunction in HF is both common and associated with poor prognosis. However, specific cut-off values of diastolic function parameters for prognostication of hard outcomes in HF have not been conclusively established. Methods and results: Analysis of full echocardiographic examination of consecutive ambulatory HFrEF and HFmrEF patients seen at a single tertiary hospital between 2010 and 2021 was retrospectively done. Data on all-cause mortality or heart failure hospitalizations were obtained from the electronic medical records and national mortality registry. Patients with > moderate left heart valvular dysfunction were excluded from the study. The final cohort included 4717 patients (75% males, median age 70 years interquartile range 61.3-78.4). After adjusting for clinical or echocardiographic variables, increased rates of mortality or HF hospitalizations were found when E/e'>10, left atrial volume index (LAVI) > 40 mL/m2, E/A ratio < 0.6, deceleration time (DT) < 180 ms, peak E-wave velocity > 0.78 m/s, and sPAP > 26 mmHg. However, no significant difference in outcomes between near-normal and normal values of E/e' (< 8 compared with 8-10) or LAVI (≤34 mL/m2 compared with LAVI 34-40 mL/m2) was found. Conclusion: In patients with HFmrEF and HFrEF, slightly abnormal diastolic indices were found to be associated with worse outcomes. Summary: We have demonstrated that in patients with heart failure with reduced and mildly reduced ejection fraction (HFrEF or HFmrEF), near-normal diastolic indices are associated with worse outcomes with the following cut-off values: max E-wave velocity > 0.78 m/s, E/e' ratio > 10, a LAVi > 40 mL/m2, DT > 180, E/A between 0.6 and 1.4, and a sPAP > 26 mmHg. Further research is needed to establish these suggested cut-off values.

Successful conservative management of left ventricular assist device candidates.

AIMS: Clinical trials comparing LVADs vs. conservative therapy were performed before the availability of novel medications or used suboptimal medical therapy. This study aimed to report that long-term stabilization of patients entering a left ventricular assist device (LVAD) programme is possible with the use of aggressive conservative therapy. This is important because the excellent clinical stabilization provided by LVADs comes at the expense of significant complications. METHODS AND RESULTS: This study was a single-centre prospective evaluation of consecutive patients with advanced heart failure (HF) fulfilling criteria for LVAD implantation based on clinical and echocardiographic characteristics, cardiopulmonary exercise test, and right heart catheterization results. Their initial therapy included inotropes, thiamine, beta-blockers, digoxin, spironolactone, hydralazine, and nitrates followed by the introduction of novel HF therapies. Coronary revascularization and cardiac resynchronization therapy were performed when indicated, and all patients were closely followed at our outpatient clinic. During the study period, 28 patients were considered suitable for LVAD implantation (mean age 63 ± 10.8 years, 92% men, 78% ischaemic, median HF duration 4 years). Clinical stabilization was achieved and maintained in 21 patients (median follow-up 20 months, range 9-38 months). Compared with baseline evaluation, cardiac index increased from 2.05 (1.73-2.28) to 2.88 (2.63-3.55) L/min/m2 , left ventricular end-diastolic diameter decreased from 65.5 (62.4-66) to 58.3 (53.8-62.5) mm, and maximal oxygen consumption increased from 10.1 (9.2-11.3) to 16.1 (15.3-19) mL/kg/min. Three patients died and only four ultimately required LVAD implantation. CONCLUSIONS: Notwithstanding the small size of our cohort, our results suggest that LVAD implantation could be safely deferred in the majority of LVAD candidates.

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.

Repetitive milrinone therapy in ambulatory advanced heart failure patients.

BACKGROUND: Advanced heart failure (HF) patients usually poorly tolerate guideline-directed HF medical therapy (GDMT) and suffer high rates of morbidity and mortality. The use of continuous inotropes in the outpatient settings is hampered by previous data showing excess morbidity. We aimed to assess the safety and efficacy of repetitive, intermittent, short-term intravenous milrinone therapy in advanced HF patients with an intention to introduce and up-titrate GDMT and improve functional class. HYPOTHESIS: Repetitive, intermittent milrinone therapy may assist with the stabilization of advanced HF patients. METHODS: Advanced HF patients treated with beta-blockers and implanted with defibrillators were initiated with repetitive, intermittent short-term intravenous milrinone therapy at our HF outpatient unit. Patients were prospectively followed with defibrillator interrogation, functional class assessment, B-natriuretic peptide (BNP) levels, and echocardiography parameters. RESULTS: The cohort included 24 patients with a mean 330 ± 240 days of milrinone therapy exposure. Mean age was 73 ± 6 years with male predominance (96%). Following milrinone therapy, median BNP levels decreased significantly (882 [286-3768] to 631 [278-1378] pg/ml, p = .017) with a significant reduction in the number of patients with New York Heart Association (NYHA) Class III and IV (p = .012, 0.013) and an increase in number of patients on GDMT. Importantly, the number of total sustained ventricular tachycardia events and HF hospitalizations did not change. CONCLUSIONS: In this small cohort of advanced HF, repetitive, intermittent, short-term milrinone therapy was found to be safe and potentially efficacious.

Intermittent inotropic therapy with levosimendan vs. milrinone in advanced heart failure patients.

AIMS: Routine, intermittent inotropic therapy (IIT) is still applied in advanced heart failure (HF) patients either as a bridge to definitive treatment or as a mean to improve quality of life (QOL), despite limited evidence to support its' use. Given recent reports of improved QOL and reduced HF hospitalization, with levosimendan compared with placebo in advanced HF patients, we aimed to assess the effects of switching a small group of milrinone-treated patients to levosimendan. This was performed as part of a protocol for changing our ambulatory HF clinic milrinone-based IIT to levosimendan. METHODS AND RESULTS: Single-centre study of consecutive ambulatory advanced HF patients that received ≥4 cycles of once-weekly milrinone IIT at our HF outpatient clinic, who were switched to levosimendan IIT. All patients had left ventricular ejection fraction ≤35%, elevated B-natriuretic peptide (BNP), and were in New York Heart Association Classes III-IV despite maximally tolerated guideline directed medical therapy. Patients were evaluated using BNP levels, echocardiography, cardio-pulmonary exercise test, and HF QOL questionnaire before and after 4 weeks of levosimendan IIT. The cohort included 11 patients, 10 (91%) were male and the mean age was 76 ± 12 years. After 4 weeks of levosimendan therapy, maximal O2 consumption improved in 8/9 (89%) by a mean of 2.28 mL/kg [95% CI -0.22-3.38, P = 0.05]. BNP levels decreased in 9/11 (82%) levosimendan treated patients, from a median of 1015 ng/L [261-1035] to 719 ng/L [294-739], (P < 0.01). QOL as measure by the EQ-5D-5L questionnaire improved in 8/11 (82%) patients after levosimendan IIT, by a median of two points [95% CO -4.14-0.37, P = 0.09]. On echocardiography, peak systolic annular velocity (S') increased after levosimendan IIT by an average of 3 cm/s [95% CI 0.16-2.10, P = 0.03]. CONCLUSIONS: In this small-scale study of ambulatory advanced HF patients, we observed improvements in right ventricular systolic function, maximal O2 consumption, and BNP after switching from milrinone to levosimendan based IIT.

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.

Age-specific mortality risk of mild diastolic dysfunction among hospitalized patients with preserved ejection fraction.

BACKGROUND: The conveyed risk of mild diastolic dysfunction (MDD) according to age had not been thoroughly studied. We aimed to investigate the mortality-risk of MDD by age-groups among inpatients with preserved ejection fraction (EF), and determine ranges of diastolic function parameters by prognosis. METHODS: In a single-center retrospective study we identified inpatients who underwent echocardiography between 2012 and 2018 and had preserved EF without significant valvulopathies. Propensity scores were used to adjust for baseline characteristics and main diagnoses at discharge. Comparisons for all-cause mortality between MDD and normal diastolic function were conducted by age groups. Using classification and regression trees (CART) modeling we determined age-specific cut-offs according to outcome. RESULTS: The cohort consisted of 15,777 inpatients. Mortality rate during a 33.9-months median follow-up was 21.6%. MDD was associated with increased mortality risk among all ages up to 90 years, thereafter no difference was detected. Adjusted hazard ratios inversely related to age - 1.99(95%CI 1.25-3.16, p = 0.004), 1.82(95%CI1.46-2.26, p < 0.001), 1.88(95%CI1.64-2.15, p < 0.001), 1.78(95%CI1.59-2.01, p < 0.001), and 1.32(95%CI0.95-1.83, p = 0.093), for 18-44, 45-59, 60-74, 75-89, and ≥90 years, respectively (Pinteraction = 0.009). New cut-offs of E/e' for ages 75-89(16), e' lateral for ages ≥90(6 cm/s), e' septal for ages 60-74(5 cm/s), and E/A ratio for ages 18-44(1.5), predicted outcome more accurately than guidelines-based recommendations. The remaining cut-offs were not better predictors compared to guidelines-based recommendations. CONCLUSIONS: MDD is a consequential finding at all ages up to 90 years among inpatients with preserved EF, although its significance decreases with age. Diastolic function of several age-groups may be better delineated by cut-offs that presage adverse prognoses. Helsinki committee approval number: 0170-17-TLV.

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.

Elevated troponin levels in patients with atrial tachyarrhythmias.

OBJECTIVE: Data regarding the significance of elevated troponin in the setting of atrial tachyarrhythmia remain inconclusive. In the present study, we aimed to explore the discriminative ability of troponin for obstructive coronary artery disease (CAD) among patients with atrial tachyarrhythmias. METHODS: We retrospectively identified patients with atrial tachyarrhythmias and elevated serum troponin levels, who underwent invasive coronary angiography during the same admission. The prevalence of obstructive CAD among these patients was compared to that of historically matched patients who underwent coronary angiography due to suspected non-ST elevation myocardial infarction and had no arrhythmias. RESULTS: Overall 318 patients with suspected non-ST elevation myocardial infarction were analyzed (n = 159 with atrial tachyarrhythmias and n = 159 without arrhythmias). Obstructive CAD was detected in 39% of patients with an arrhythmia compared to 85.5% in the control group (P < 0.001). A multivariable analysis demonstrated that parameters associated with obstructive CAD among patient with atrial tachyarrhythmias and elevated troponin were diabetes mellitus [odds ratio (OR) 2.7, 95% confidence interval (CI) 1.23-5.91, P = 0.013], prior ischemic heart disease (OR 4.48, 95% CI 1.93-10.4, P < 0.001) and troponin level (OR 3.18 for every 1000 ng/L increment, 95% CI 1.85-5.48, P < 0.001). CONCLUSIONS: Elevated troponin is not a reliable indicator for the presence of underlying obstructive CAD among patients who present with atrial tachyarrhythmias. Risk stratification of these patients should rely on the degree of troponin elevation, and the presence of diabetes mellitus and prior ischemic heart disease.