Electromechanical Window and Spontaneous Ventricular Tachyarrhythmias in Takotsubo Syndrome.

QT interval prolongation is common in patients hospitalized with Takotsubo syndrome (TTS), however, only a minority experience ventricular tachyarrhythmias. Our aim was to characterize the electromechanical window (EMW) in patients with TTS and to evaluate its association with ventricular tachyarrhythmias. We preformed aretrospective analysis of 84 patients hospitalized with TTS in the Tel-Aviv Medical Center between 2013 and 2022. All patients underwent a comprehensive echocardiographic evaluation and the EMW was calculated by subtracting the QT interval from the QRS onset to the aortic valve closure obtained from a continuous-wave Doppler for the same beat. Of the 84 patients with TTS, 74 (88%) were female and the mean age was 70 ± 11 years. The mean left ventricular ejection fraction was 42 ± 8%. The EMW was negative in 81 patients (96%), and the mean EMW was -69 ± 50 ms. Ventricular tachyarrhythmias occurred in 7 patients (8%). The EMW of patients who experienced ventricular tachyarrhythmias was more negative than patients who did not (-133 ± 23 ms vs -63 ± 48 ms, p = 0.001). In the univariate analysis, EMW and QT were associated with ventricular tachyarrhythmias (univariate odds ratio [OR]EMW 1.03, 95% confidence interval [CI] 1.01 to 1.05, p = 0.003 and univariate ORQTc 1.02, 95% CI 1.01 to 1.03, p = 0.02); however, only EMW remained significant in the multivariate analysis (OREMW 1.03 95% CI 1.03 to 1.05, p = 0.023). EMW was more effective than corrected QT interval in identifying patients who had ventricular tachyarrhythmias (AUCEMW: 0.89, 95% CI 0.82 to 0.97 vs AUCQTc 0.77, 95% CI 0.61 to 0.93, p = 0.02), and a cut-off value of -108 ms was predictive of ventricular tachyarrhythmias with a sensitivity of 86% and a specificity of 79%. In conclusion, EMW is negative in patients with TTS and is associated with increased risk for ventricular tachyarrhythmias. The role of EMW in the risk stratification of patients with TTS warrants further investigation.

The Mechanism of Effort Intolerance in Patients with Peripheral Arterial Disease: A Combined Stress Echocardiography and Cardiopulmonary Exercise Test.

AIM: We used a combined stress echocardiography and cardiopulmonary exercise test (CPET) to explore effort intolerance in peripheral arterial disease (PAD) patients. METHODS: Twenty-three patients who had both PAD and coronary artery disease (CAD) were compared with twenty-four sex- and age-matched CAD patients and fifteen normal controls using a symptom-limited ramp bicycle CPET 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. RESULTS: Along the stages of exercise (unloaded; anaerobic threshold; peak), in PAD + CAD patients compared with CAD or controls, diastolic function worsened (p = 0.051 and p = 0.013, respectively), and oxygen consumption (p < 0.001 and p < 0.001, respectively) and oxygen pulse (p = 0.0024 and p = 0.0027, respectively) were reduced. Notably, oxygen pulse was blunted due to an insufficient increase in both stroke volume (p = 0.025 and p = 0.028, respectively) and peripheral oxygen extraction (p = 0.031 and p = 0.038, respectively). Chronotropic incompetence was more prevalent in PAD patients and persisted after correction for beta-blocker use (62% vs. 42% and 11%, respectively). CONCLUSIONS: In PAD patients, exercise limitation is associated with diastolic dysfunction, chronotropic incompetence and peripheral factors.

Cardiologic Manifestations in Omicron-Type Versus Wild-Type COVID-19: A Systematic Echocardiographic Study.

Background Information about the cardiac manifestations of the Omicron variant of COVID-19 is limited. We performed a systematic prospective echocardiographic evaluation of consecutive patients hospitalized with the Omicron variant of COVID-19 infection and compared them with similarly recruited patients were propensity matched with the wild-type variant. Methods and Results A total of 162 consecutive patients hospitalized with Omicron COVID-19 underwent complete echocardiographic evaluation within 24 hours of admission and were compared with propensity-matched patients with the wild-type variant (148 pairs). Echocardiography included left ventricular (LV) systolic and diastolic, right ventricular (RV), strain, and hemodynamic assessment. Echocardiographic parameters during acute infection were compared with historic exams in 62 patients with the Omicron variant and 19 patients with the wild-type variant who had a previous exam within 1 year. Of the patients, 85 (53%) had a normal echocardiogram. The most common cardiac pathology was RV dilatation and dysfunction (33%), followed by elevated LV filling pressure (E/e' ≥14, 29%) and LV systolic dysfunction (ejection fraction <50%, 10%). Compared with the matched wild-type cohort, patients with Omicron had smaller RV end-systolic areas (9.3±4 versus 12.3±4 cm2; P=0.0003), improved RV function (RV fractional-area change, 53.2%±10% versus 39.7%±13% [P<0.0001]; RV S', 12.0±3 versus 10.7±3 cm/s [P=0.001]), and higher stroke volume index (35.6 versus 32.5 mL/m2; P=0.004), all possibly related to lower mean pulmonary pressure (34.6±12 versus 41.1±14 mm Hg; P=0.0001) and the pulmonary vascular resistance index (P=0.0003). LV systolic or diastolic parameters were mostly similar to the wild-type variant-matched cohort apart from larger LV size. However, in patients who had a previous echocardiographic exam, these LV abnormalities were recorded before acute Omicron infection, but not in the wild-type cohort. Numerous echocardiographic parameters were associated with higher in-hospital mortality (LV ejection fraction, stroke volume index, E/e', RV S'). Conclusions In patients with Omicron, RV function is impaired to a lower extent compared with the wild-type variant, possibly related to the attenuated pulmonary parenchymal and/or vascular disease. LV systolic and diastolic abnormalities are as common as in the wild-type variant but were usually recorded before acute infection and probably reflect background cardiac morbidity. Numerous LV and RV abnormalities are associated with adverse outcome in patients with Omicron.

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.

Systematic lung ultrasound in Omicron-type vs. wild-type COVID-19.

AIMS: Preliminary data suggested that patients with Omicron-type-Coronavirus-disease-2019 (COVID-19) have less severe lung disease compared with the wild-type-variant. We aimed to compare lung ultrasound (LUS) parameters in Omicron vs. wild-type COVID-19 and evaluate their prognostic implications. METHODS AND RESULTS: One hundred and sixty-two consecutive patients with Omicron-type-COVID-19 underwent LUS within 48 h of admission and were compared with propensity-matched wild-type patients (148 pairs). In the Omicron patients median, first and third quartiles of the LUS-score was 5 [2-12], and only 9% had normal LUS. The majority had either mild (≤5; 37%) or moderate (6-15; 39%), and 15% (≥15) had severe LUS-score. Thirty-six percent of patients had patchy pleural thickening (PPT). Factors associated with LUS-score in the Omicron patients included ischaemic-heart-disease, heart failure, renal-dysfunction, and C-reactive protein. Elevated left-filling pressure or right-sided pressures were associated with the LUS-score. Lung ultrasound-score was associated with mortality [odds ratio (OR): 1.09, 95% confidence interval (CI): 1.01-1.18; P = 0.03] and with the combined endpoint of mortality and respiratory failure (OR: 1.14, 95% CI: 1.07-1.22; P < 0.0001). Patients with the wild-type variant had worse LUS characteristics than the matched Omicron-type patients (PPT: 90 vs. 34%; P < 0.0001 and LUS-score: 8 [5, 12] vs. 5 [2, 10], P = 0.004), irrespective of disease severity. When matched only to the 31 non-vaccinated Omicron patients, these differences were attenuated. CONCLUSION: Lung ultrasound-score is abnormal in the majority of hospitalized Omicron-type patients. Patchy pleural thickening is less common than in matched wild-type patients, but the difference is diminished in the non-vaccinated Omicron patients. Nevertheless, even in this milder form of the disease, the LUS-score is associated with poor in-hospital outcomes.

QT Interval Prolongation Is a Novel Predictor of 1-Year Mortality in Patients With COVID-19 Infection.

Background: QT interval prolongation is common in critically ill patients and is associated with increased mortality. However, the predictive value of a prolonged corrected QT interval (QTc) for myocardial injury and long-term mortality among patients hospitalized with COVID-19 infection is not well known. Purpose: To evaluate the association of prolonged QTc with myocardial injury and with 1-year mortality among patients hospitalized with COVID-19 infection. Materials and Methods: A total of 335 consecutive patients hospitalized with COVID-19 infection were prospectively studied. All patients underwent a comprehensive echocardiographic evaluation within 48 h from admission. Using the Bazett formula, the QTc interval was calculated from the first ECG tracing recorded at the ER. QTc ≥ 440 ms in males and ≥450 ms in females was considered prolonged. Patients with elevated cardiac biomarkers and/or echocardiographic signs of myocardial dysfunction were considered to have myocardial injury. The predictive value of QTc prolongation for myocardial injury was calculated using a multivariate binary regression model. One-year mortality rate of patients with and without QTc prolongation was compared using the log-rank test, and a multivariate Cox regression model adjusting for multiple covariates was performed to evaluate the 1-year mortality risk. Results: One-hundred and nine (32.5%) patients had a prolonged QTc. Compared to patients without QTc prolongation, patients with prolonged QTc were older (70 ± 14.4 vs. 62.7 ± 16.6, p < 0.001), had more comorbidities, and presented with a more severe disease. Prolonged QTc was an independent predictor for severe or critical disease (adjusted HR 2.14, 95% CI 1.3-3.5; p = 0.002) and myocardial injury (adjusted HR 2.07, 95% CI 1.22-3.5; p = 0.007). One-year mortality of patients with prolonged QTc was higher than those with no QTc prolongation (40.4% vs. 15.5; p < 0.001). Following adjustment to multiple covariates including myocardial injury and disease severity, QTc prolongation was found to be associated with increased 1-year mortality risk (HR 1.69, 95% CI 1.06-2.68, p = 0.027). Conclusion: Prolonged QTc is associated with disease severity, myocardial injury and 1-year mortality among patients hospitalized with COVID-19 infection.

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.

Serological Response to the BNT162b2 COVID-19 mRNA Vaccine in Adolescent and Young Adult Kidney Transplant Recipients.

BACKGROUND: Initial reports in adult kidney transplant recipients (KTR) indicate low immunogenicity after 2 doses of the BNT162b2 COVID-19 mRNA vaccine. We describe the immunogenicity of this vaccine compared to the serologic response in naturally infected COVID-19 positive adolescent and young adult KTR. METHODS: For this prospective observational study, the study group included 38 KTR who received 2 doses of the tested vaccine, and the control group included 14 KTR who had a previous polymerase chain reaction-confirmed COVID-19 infection. RESULTS: The mean age was 18 ± 3 y. Positive serologic responses were observed in 63% and 100% of the study and control groups, respectively (P = 0.01). Antibody titers were almost 30-fold higher in the control than the study group (median [interquartile range (IQR)]: 2782 [1908-11 000] versus 100.3 [4.7-1744] AU/mL, P < 0.001), despite the longer time from the COVID-19 infection to serologic testing compared to time from vaccination (median [IQR]: 157.5 [60-216] versus 37 [20.5-53] d, P = 0.011). Among vaccinated patients, higher proportions of those seronegative than seropositive were previously treated with rituximab (50% versus 8%, P = 0.01). Time from the second vaccine dose to serologic testing was longer in seropositive than seronegative patients (median [IQR]: 24.5 [15-40] versus 46 [27-56] d, P = 0.05). No patient developed symptomatic COVID-19 disease postvaccination. CONCLUSIONS: The BNT162b2 COVID-19 mRNA vaccine yielded higher positive antibody response in adolescent and young adult KTR than previously reported for adult KTR. Antibody titers after vaccination were significantly lower than following COVID-19 infection. Longer time may be required to mount appropriate humoral immunity to vaccination in KTR.