The Role of Inflammation in Early Left Ventricular Thrombus Formation Following ST-Elevation Myocardial Infarction-A Matched Case-Control Study.

BACKGROUND: There is limited data on the association between inflammation and the formation of early left ventricular thrombus (LVT) following ST-elevation myocardial infarction (STEMI). This study aimed to explore the predictive value of several inflammatory biomarkers for LVT formation following STEMI. METHODS AND RESULTS: Our cohort included 2534 consecutive patients admitted to the cardiac intensive care unit (CICU) with STEMI. The final analysis included 51 patients with LVT and 102 patients without LVT, matched for age, sex, anterior infarct and ejection fraction. Upon admission, patients with LVT had higher white blood cell counts (WBC) (12.8 ± 7 vs. 12.4 ± 4 ×103/µL, p = 0.01), higher absolute neutrophil counts (10.5 ± 4 vs. 8.6 ± 4 ×103/µL, p = 0.003), neutrophil-to-lymphocyte ratio (8.2 ± 6 vs. 4.8 ± 4, p = 0.04), and C-reactive protein (CRP) levels (35.9 ± 62 vs. 18.6 ± 40 mg/L, p = 0.04). Peak values for WBC and CRP were also higher in the LVT group (17.8 ± 8 vs. 14.6 ± 5 ×103/µL, p = 0.003 and 95.8 ± 82 vs. 64.2 ± 76 mg/L, p = 0.02, respectively). In univariate regression analysis, WBC upon admission (OR: 1.12, 95% CI: 1.02-1.21, p = 0.02), peak WBC (OR: 1.09, 95% CI: 1.02-1.17, p = 0.009), neutrophil count upon admission (OR: 1.15, 95% CI: 1.04-1.26, p = 0.004), and peak CRP (OR: 1.01, 95% CI: 1-1.01, p = 0.03) predicted LVT formation, which was also evident in multivariate regression models. CONCLUSION: WBC and neutrophil counts upon admission, as well as peak WBC and CRP, have additional predictive value for LVT formation following STEMI, beyond classical risk factors.

Routine Ankle-Brachial Index (ABI) measurement: a window into atherosclerosis and early left ventricular dysfunction in patients diagnosed with cancer.

BACKGROUND: Cancer therapy is considered to cause accelerated ischemia. Ankle-Brachial Index (ABI) measurement is an inexpensive, simple, available test for the early diagnosis of peripheral artery disease (PAD); however, it is not performed routinely. We aimed to evaluate the role of routine ABI measurement for the diagnosis of PAD among patients diagnosed with cancer and whether it correlates with left ventricular (LV) dysfunction. METHODS: A retrospective, single-center study including patients diagnosed with cancer at Tel Aviv Sourasky Medical Center. The cohort included patients performing routine ABI and LV global longitudinal strain (GLS) echocardiography. The primary endpoint was the prevalence of PAD and whether it correlates with LV dysfunction, defined by LV GLS absolute value < 19%. The secondary composite endpoint evaluated the association between reduced ABI to LV dysfunction and all-cause mortality. RESULTS: Among 226 patients, PAD was diagnosed in 14 patients (6%). We revealed a positive correlation between ABI and LV GLS (r = 0.22, p < 0.01) with a reduced mean ABI score among patients with reduced LV GLS. A reduced mean ABI was observed among the positive composite endpoint group; however, it was not statistically significant (p = 0.35). CONCLUSIONS: We report, for the first time to our knowledge, the routine use of ABI testing among patients diagnosed with cancer. ABI showed a significant correlation to LV GLS, implying a potential tool in the early diagnosis of atherosclerosis and cardiotoxicity. Considering its low cost and availability, future prospective trials are needed to integrate its role in routine assessment.

Prognostic Value of Echocardiographic-derived Stroke Volume in Severe Primary Mitral Regurgitation.

AIM: Studies have demonstrated the importance of forward flow, and specifically of stroke volume (SV) and SV index (SVI), as prognostic markers in different cardiovascular diseases. Here we aimed to evaluate the association between SV and SVI thresholds and prognosis in patients with severe primary mitral regurgitation (MR). METHODS AND RESULTS: The association between either SV (<55, 55-70 and >70ml) or SVI (<30, 30-35 and >35mL/m²) thresholds and all-cause mortality and heart failure (HF) hospitalizations was examined in a retrospective analysis of 283 patients (60% male, median age 70 years, IQR 58-82) with severe primary MR, normal left ventricular size and systolic function and no other significant left-sided valvular abnormalities. Compared with normal values, SV<55ml was found to be associated with worse outcomes (HR 1.8, IQR 1.1-2.8, P=0.016), whereas SV between 55-70ml was not. A non-significant trend for worse outcomes was noted for SVI<35ml/m² compared with normal SVI. CONCLUSION: In patients with severe primary MR, SV<55ml was found to be associated with increased rates of HF hospitalization and all-cause mortality. This easily obtainable parameter may allow for better risk stratification of patients with primary MR.

Benefit of isolated surgical valve repair or replacement for functional tricuspid regurgitation and long-term outcomes stratified by the TRI-SCORE.

BACKGROUND AND AIMS: Severe tricuspid regurgitation (TR) is associated with increased mortality rates, but benefit of its correction and ideal timing are not clearly determined. This study aimed to identify patient subsets who might benefit from surgery. METHODS: In TRIGISTRY, an international cohort study of consecutive patients with severe isolated functional TR (33 centers, 10 countries), survival rates up to 10 years were compared between patients who underwent isolated tricuspid valve (TV) surgery (repair or replacement) and those conservatively managed, overall and according to TRI-SCORE category (low: ≤3, intermediate: 4-5, high: ≥6). RESULTS: 1,217 were managed conservatively, and 551 underwent isolated TV surgery (200 repairs, 351 replacements). TRI-SCORE distribution was 33% low, 32% intermediate, and 35% high. At 10 years, survival rates were similar between surgical and conservative management (41% vs. 36%; hazard ratio [HR] 0.97; 95% confidence interval [CI] 0.88-1.08, P=0.57). Surgery improved survival compared to conservative management in the low TRI-SCORE category (72% vs. 44%; HR 0.27; 95% CI 0.20-0.37, P<0.0001), but not in the intermediate (36% vs. 37%, HR 1.17; 95%CI 0.98-1.40, P=0.09) or high categories (20% vs. 24%; HR 1.06; 95% CI 0.91-1.25, P=0.45). Both repair and replacement improved survival in the low TRI-SCORE category (84% and 61% vs. 44%; HR 0.11; 95% CI 0.06-0.19, P<0.0001, and HR 0.65; 95% CI 0.47-0.90, P=0.009). Repair showed benefit in the intermediate category (59% vs. 37%; HR 0.49; 95% CI 0.35-0.68, P<0.0001) while replacement was possibly harmful (25% vs. 37%; HR 1.43; 95% CI 1.18-1.72, P=0.0002). CONCLUSIONS: Higher survival rates were observed with repair than replacement and benefit of intervention declined as TRI-SCORE increased with no benefit of any type of surgery in the high TRI-SCORE category. These results emphasize the importance of timely intervention and patient selection to achieve the best outcomes and the need for randomized controlled trials. TRIAL REGISTRATION: TRIGISTRY: ClinicalTrials.gov, NCT05825898.

Tricuspid regurgitation in the context of severe left-sided valvular disease: Patients characteristics and outcome.

Background: We aimed to assess the characteristics, management and long-term prognosis of a cohort of patients with multiple valvular disease, focusing on the context of severe mitral or aortic disease with concomitant significant tricuspid regurgitation (TR). Methods: After using a propensity score matching for age, 975 patients with ≥ moderate TR, diagnosed at our centers from 2012 to 2020, were included and divided in four groups, including isolated TR patients as reference group. Primary endpoint was all-cause death (ACD), secondary endpoint was the composite of heart failure (HF) hospitalization + any valvular intervention. Results: Patients with isolated TR (356, 37 %) had more history of atrial fibrillation and were more often asymptomatic and with preserved left-ventricular ejection fraction (LVEF). Patients with severe mitral regurgitation (MR) + TR (466, 48 %) showed higher rates of concomitant coronary artery disease, advanced functional class symptoms and larger left atrial volumes. Severe aortic stenosis (AS) patients (131, 13 %) were older, with more comorbidities and lower LVEF. Patients with severe aortic regurgitation and TR (22, 2 %) were younger, with larger LV dimensions and higher pulmonary arterial pressures.After a median follow-up of 2.8 years, both endpoints were univariably more frequent in patients with severe AS + TR (all p < 0.001), but after comprehensive adjustment difference in the primary endpoint became insignificant, underscoring the serious outcomes of all significant TR groups significantly. Overall, in 44 (5 %) patients tricuspid intervention was performed, with no differences between groups in term of frequency of concomitant or staged tricuspid valve surgical treatment. Conclusions: In the context of severe left-sided VD, concomitant significant TR is common, and each subtype presents with different clinical and echocardiographic features: patients with severe AS and TR have considerable worse prognosis, although comprehensive adjustment reflected the poor outcomes affecting all types of patients with significant TR. In this scenario, TR was profoundly undertreated.

Sex-related differences in the association between septal wall thickness and survival.

Background: In many conditions characterised by septal hypertrophy, females have been shown to have worse outcomes compared to males. In clinical practice and research, similar cutoff points for septal hypertrophy are still used for both sexes. Here, we explore the association between different cutoff points for septal hypertrophy and survival in relation to sex. Methods and results: We performed a retrospective analysis of consecutive patients undergoing echocardiography between March 2010 and February 2021 in a large tertiary referral centre. A total of 70,965 individuals were included. Over a mean follow-up period of 59.1 ± 37 months, 9631 (25 %) males and 8429 (26 %) females died. When the same cutoff point for septal hypertrophy was used for both sexes, females had worse prognosis than males. The impact of septal hypotrophy on survival became statistically significant at a lower threshold in females compared to males: 11.1 mm (HR 1.13, CI 95 %:1.03-1.23, p = 0.01) vs 13.1 mm (HR 1.21, CI 95 %: 1.12-1.32, p < 0.001). However, when indexed wall thickness was used, the cutoff points were 6 mm/body surface area (BSA) (HR 1.08, CI 95 %: 1-1.18, p = 0.04) and 6.2 mm/BSA (HR 1.07, CI 95 %: 1-1.15, p = 0.05) for females and males, respectively. Conclusions: Septal hypertrophy is associated with increased mortality at a lower threshold in females than in males. This may account for the worse prognosis reported in females in many conditions characterised by septal hypertrophy. Applying a lower absolute value or using indexed measurements may facilitate early diagnosis and improve prognostication in females.

Reappraisal of the Concept and Implications of Pulmonary Hypertension in Degenerative Mitral Regurgitation.

BACKGROUND: European and U.S. clinical guidelines diverge regarding pulmonary hypertension (PHTN) in degenerative mitral regurgitation (DMR). Gaps in knowledge underpinning these divergences affect risk assessment and management recommendations attached to systolic pulmonary pressure (SPAP) in DMR. OBJECTIVES: This study sought to define PHTN links to DMR severity, prognostic thresholds, and independent outcome impact in a large quantitative DMR registry. METHODS: This study gathered a large multicentric registry of consecutive patients with isolated moderate-to-severe DMR, with DMR and SPAP quantified prospectively at diagnosis. RESULTS: In 3,712 patients (age 67 ± 15 years, 36% women) with ≥ moderate-to-severe DMR, effective regurgitant orifice (ERO) was 0.42 ± 0.19 cm2, regurgitant volume 66 ± 327 mL/beat and SPAP 41 ± 16 mm Hg. Spline-curve analysis showed excess mortality under medical management emerging around SPAP 35 mm Hg and doubling around SPAP 50 mm Hg. Accordingly, severe pulmonary hypertension (sPHTN) (SPAP ≥50 mm Hg) was detected in 916 patients, moderate pulmonary hypertension (mPHTN) (SPAP 35-49 mm Hg) in 1,128, and no-PHTN (SPAP <35 mm Hg) in 1,668. Whereas SPAP was strongly associated with DMR-ERO, nevertheless excess mortality with sPHTN (adjusted HR: 1.65; 95% CI: 1.24-2.20) and mPHTN (adjusted HR: 1.44; 95% CI: 1.11-1.85; both P ≤ 0.005) was observed independently of ERO and all baseline characteristics and in all patient subsets. Nested models demonstrated incremental prognostic value of mPHTN and sPHTN (all P < 0.0001). Despite higher operative risk with mPHTN and sPHTN, DMR surgical correction was followed by higher survival in all PHTN ranges with strong survival benefit of early surgery (<3 months). Postoperatively, excess mortality was abolished (P ≥ 0.30) in mPHTN, but only abated in sPHTN. CONCLUSIONS: This large international registry, with prospectively quantified DMR and SPAP, demonstrates a Doppler-defined PHTN impact on mortality, independent of DMR severity. Crucially, it defines objectively the new and frequent mPHTN range, independently linked to excess mortality under medical management, which is abolished by DMR correction. Thus, at DMR diagnosis, Doppler-SPAP measurement defining these new PHTN ranges, is crucial to guiding DMR management.

Predicting the Outcomes of Inpatient Cardiac Evaluation for Syncope Using Validated Risk Scores.

BACKGROUND: Validated syncope risk scores were aimed to predict a cardiac etiology and are mainly used in the decision of hospital admission. Whether these scores could also predict the outcomes of inpatient cardiac evaluation is unknown and was the subject of our study. METHODS: This was an observational study including consecutive patients admitted for syncope evaluation. All patients completed prolonged electrocardiogram monitoring and an echocardiography before discharge. The area under the receiver-operating characteristic curve (AUC) was used to evaluate the ability of validated risk scores to predict positive inpatient findings. Subsequently, a multivariate regression was performed to identify independent predictors for positive cardiac evaluation, which were then incorporated into the best predictive risk scores. RESULTS: Three hundred ninety-seven patients were included, 56 (14%) with a positive inpatient cardiac evaluation. The Osservatorio Epidemiologico sulla Sincope Lazio and Canadian Syncope Risk Score achieved the largest AUC (0.701, 95% confidence interval [CI] 0.63-0.77 and 0.694, 95% CI 0.62-0.77, respectively). Yet, all scores provided relatively high sensitivity with low specificity. Multivariate regression revealed age ≥75 (adjusted odds ratio 3.50, 95% CI 1.5-7.9) and abnormal cardiac auscultation (adjusted odds ratio 4.79, 95% CI 2.5-9.1) to be independent predictors. Incorporating these factors led to a significantly higher prediction ability of the Osservatorio Epidemiologico sulla Sincope Lazio (AUC of 0.787, P < .01) and Canadian Syncope Risk Score (AUC 0.778, P < .01) modified scores. CONCLUSIONS: Current syncope risk scores provide limited prediction ability for the outcomes of inpatient cardiac syncope work-up. One should specifically consider age > 75 years and either cardiac murmur or irregular heart rate on examination very significant in implying a cardiac etiology for syncope. Although these factors may be obvious, current risk scores can be interpreted in such a fashion that ignores the importance of findings extracted from a good history and physical examination.

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.

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.

Sodium-glucose co-transporter-2 inhibitors in patients treated with immune checkpoint inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the prognosis of cancer. Diabetes mellitus (DM) has been shown to have a negative effect on patients treated with ICIs. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are effective antidiabetic therapies associated with reduced all-cause mortality and cardiovascular (CV) outcomes. OBJECTIVE: To evaluate the prognostic value of SGLT2i on all-cause mortality and cardiotoxicity among patients treated with ICIs. METHODS: We performed a retrospective analysis of patients diagnosed with cancer and type 2 DM (DM2) and treated with ICIs at our center. Patients were divided into two groups according to baseline treatment with or without SGLT2i. The primary endpoint was all-cause mortality and the secondary endpoint was MACE, including myocarditis, acute coronary syndrome, heart failure, and arrhythmia. RESULTS: The cohort included 119 patients, with 24 (20%) patients assigned to the SGLT2i group. Both groups exhibited a comparable prevalence of cardiac risk factors, although the SGLT2i group displayed a higher incidence of ischemic heart disease. Over a median follow-up of 28 months, 61 (51%) patients died, with a significantly lower all-cause mortality rate in the SGLT2i group (21% vs. 59%, p = 0.002). While there were no significant differences in MACE, we observed zero cases of myocarditis and atrial fibrillation in the SGLT2i, compared to 2 and 6 cases in the non-SGLT2i group. CONCLUSIONS: SGLT2i therapy was associated with a lower all-cause mortality rate in patients diagnosed with cancer and DM2 and treated with ICIs. Further studies are needed to understand the mechanism and evaluate its benefit on cardiotoxicity.

TRI-SCORE and benefit of intervention in patients with severe tricuspid regurgitation.

BACKGROUND AND AIMS: Benefit of tricuspid regurgitation (TR) correction and timing of intervention are unclear. This study aimed to compare survival rates after surgical or transcatheter intervention to conservative management according to a TR clinical stage as assessed using the TRI-SCORE. METHODS: A total of 2,413 patients with severe isolated functional TR were enrolled in TRIGISTRY (1217 conservatively managed, 551 isolated tricuspid valve surgery, and 645 transcatheter valve repair). The primary endpoint was survival at 2 years. RESULTS: The TRI-SCORE was low (≤3) in 32%, intermediate (4-5) in 33%, and high (≥6) in 35%. A successful correction was achieved in 97% and 65% of patients in the surgical and transcatheter groups, respectively. Survival rates decreased with the TRI-SCORE in the three treatment groups (all P < .0001). In the low TRI-SCORE category, survival rates were higher in the surgical and transcatheter groups than in the conservative management group (93%, 87%, and 79%, respectively, P = .0002). In the intermediate category, no significant difference between groups was observed overall (80%, 71%, and 71%, respectively, P = .13) but benefit of the intervention became significant when the analysis was restricted to patients with successful correction (80%, 81%, and 71%, respectively, P = .009). In the high TRI-SCORE category, survival was not different to conservative management in the surgical and successful repair group (61% and 68% vs 58%, P = .26 and P = .18 respectively). CONCLUSIONS: Survival progressively decreased with the TRI-SCORE irrespective of treatment modality. Compared to conservative management, an early and successful surgical or transcatheter intervention improved 2-year survival in patients at low and, to a lower extent, intermediate TRI-SCORE, while no benefit was observed in the high TRI-SCORE category.

The prognostic value of beta-1 blockers in patients with non-small-cell lung carcinoma treated with pembrolizumab.

BACKGROUND: Immune checkpoint inhibitors (ICIs) such as pembrolizumab have revolutionized the treatment of metastatic non-small cell lung cancer (mNSCLC). Beta-adrenergic activation contributes to cancer initiation and progression. While non-selective beta-blocker were found to improve the efficacy of ICIs therapy, the role of beta-1 (ß1)-selective -blocker (ß1B) in lung cancer patients is unknown. OBJECTIVE: To evaluate the effect of ß1B on overall survival (OS) and progression-free survival (PFS) in patients diagnosed with mNSCLC and treated with pembrolizumab. METHODS: We performed a retrospective analysis of patients diagnosed with mNSCLC and treated with first-line pembrolizumab at our center. RESULTS: Of 200 eligible patients, 53 (27%) were pretreated with ß1B. Patients in the ß1B cohort were older (73 ± 8 vs. 67 ± 10 years, p < 0.001) with a higher prevalence of cardiac risk factors and cardiovascular (CV) diseases including ischemic heart disease (32% vs. 16%, p = 0.010), heart failure (9% vs. 3%, p = 0.043) and atrial fibrillation (23% vs. 3%, p < 0.001). Compared to the non-ß1B group, patient pretreated with ß1B had a significant shorter median OS (12 vs. 24 months, p = 0.004) and PFS (6 vs. 8 months, p < 0.001). In a multivariate analysis, including all CV risk factors and diseases, the use of baseline ß1B was a strong and independent predictor for accelerated disease progression (HR 1.92, 95%CI 1.32-2.79, p < 0.001) and shorter OS (HR 1.8, 95%, CI 1.18-2.75, p = 0.007). CONCLUSIONS: The use of baseline ß1B showed a strong and independent association for shorter OS and PFS in patients diagnosed with mNSCLC and treated with pembrolizumab.

An Integrative, Multiparametric Approach to Tricuspid Regurgitation Evaluation: A Case-Based Illustration.

Echocardiography is the first-line modality for assessing tricuspid regurgitation (TR). In addition to evaluation of the mechanism of TR, echocardiography can provide quantitative parameters of TR severity and assess hemodynamics. This case series demonstrates the importance of integrating multiple parameters in the evaluation of TR and the role of multimodality imaging. (Level of Difficulty: Intermediate.).

American Society of Echocardiography COVID-19 Statement Update: Lessons Learned and Preparation for Future Pandemics.

The COVID-19 pandemic has evolved since the publication of the initial American Society of Echocardiography (ASE) statements providing guidance to echocardiography laboratories. In light of new developments, the ASE convened a diverse, expert writing group to address the current state of the COVID-19 pandemic and to apply lessons learned to echocardiography laboratory operations in future pandemics. This statement addresses important areas specifically impacted by the current and future pandemics: (1) indications for echocardiography, (2) application of echocardiographic services in a pandemic, (3) infection/transmission mitigation strategies, (4) role of cardiac point-of-care ultrasound/critical care echocardiography, and (5) training in echocardiography.

Tricuspid Valve Academic Research Consortium Definitions for Tricuspid Regurgitation and Trial Endpoints.

Interest in the pathophysiology, etiology, management, and outcomes of patients with tricuspid regurgitation (TR) has grown in the wake of multiple natural history studies showing progressively worse outcomes associated with increasing TR severity, even after adjusting for multiple comorbidities. Historically, isolated tricuspid valve surgery has been associated with high in-hospital mortality rates, leading to the development of transcatheter treatment options. The aim of this first Tricuspid Valve Academic Research Consortium document is to standardize definitions of disease etiology and severity, as well as endpoints for trials that aim to address the gaps in our knowledge related to identification and management of patients with TR. Standardizing endpoints for trials should provide consistency and enable meaningful comparisons between clinical trials. A second Tricuspid Valve Academic Research Consortium document will focus on further defining trial endpoints and will discuss trial design options.

Tricuspid Valve Academic Research Consortium Definitions for Tricuspid Regurgitation and Trial Endpoints.

Interest in the pathophysiology, etiology, management, and outcomes of patients with tricuspid regurgitation (TR) has grown in the wake of multiple natural history studies showing progressively worse outcomes associated with increasing TR severity, even after adjusting for multiple comorbidities. Historically, isolated tricuspid valve surgery has been associated with high in-hospital mortality rates, leading to the development of transcatheter treatment options. The aim of this first Tricuspid Valve Academic Research Consortium document is to standardize definitions of disease etiology and severity, as well as endpoints for trials that aim to address the gaps in our knowledge related to identification and management of patients with TR. Standardizing endpoints for trials should provide consistency and enable meaningful comparisons between clinical trials. A second Tricuspid Valve Academic Research Consortium document will focus on further defining trial endpoints and will discuss trial design options.