Tricuspid Regurgitation: From Imaging to Clinical Trials to Resolving the Unmet Need for Treatment.

Tricuspid regurgitation (TR) is a highly prevalent and heterogeneous valvular disease, independently associated with excess mortality and high morbidity in all clinical contexts. TR is profoundly undertreated by surgery and is often discovered late in patients presenting with right-sided heart failure. To address the issue of undertreatment and poor clinical outcomes without intervention, numerous structural tricuspid interventional devices have been and are in development, a challenging process due to the unique anatomic and physiological characteristics of the tricuspid valve, and warranting well-designed clinical trials. The path from routine practice TR detection to appropriate TR evaluation, to conduction of clinical trials, to enriched therapeutic possibilities for improving TR access to treatment and outcomes in routine practice is complex. Therefore, this paper summarizes the key points and methods crucial to TR detection, quantitation, categorization, risk-scoring, intervention-monitoring, and outcomes evaluation, particularly of right-sided function, and to clinical trial development and conduct, for both interventional and surgical groups.

Exercise Stress Echocardiography of the Right Ventricle and Pulmonary Circulation.

BACKGROUND: Exercise echocardiography is used for assessment of pulmonary circulation and right ventricular function, but limits of normal and disease-specific changes remain insufficiently established. OBJECTIVES: The objective of this study was to explore the physiological vs pathologic response of the right ventricle and pulmonary circulation to exercise. METHODS: A total of 2,228 subjects were enrolled: 375 healthy controls, 40 athletes, 516 patients with cardiovascular risk factors, 17 with pulmonary arterial hypertension, 872 with connective tissue diseases without overt pulmonary hypertension, 113 with left-sided heart disease, 30 with lung disease, and 265 with chronic exposure to high altitude. All subjects underwent resting and exercise echocardiography on a semirecumbent cycle ergometer. All-cause mortality was recorded at follow-up. RESULTS: The 5th and 95th percentile of the mean pulmonary artery pressure-cardiac output relationships were 0.2 to 3.5 mm Hg.min/L in healthy subjects without cardiovascular risk factors, and were increased in all patient categories and in high altitude residents. The 5th and 95th percentile of the tricuspid annular plane systolic excursion to systolic pulmonary artery pressure ratio at rest were 0.7 to 2.0 mm/mm Hg at rest and 0.5 to 1.5 mm/mm Hg at peak exercise, and were decreased at rest and exercise in all disease categories and in high-altitude residents. An increased all-cause mortality was predicted by a resting tricuspid annular plane systolic excursion to systolic pulmonary artery pressure <0.7 mm/mm Hg and mean pulmonary artery pressure-cardiac output >5 mm Hg.min/L. CONCLUSIONS: Exercise echocardiography of the pulmonary circulation and the right ventricle discloses prognostically relevant differences between healthy subjects, athletes, high-altitude residents, and patients with various cardio-respiratory conditions. (Right Heart International NETwork During Exercise in Different Clinical Conditions; NCT03041337).

Multicomponent intervention for frail and pre-frail older adults with acute cardiovascular conditions: The TARGET-EFT randomized clinical trial.

BACKGROUND: Hospitalization for cardiovascular disease (CVD) may be complicated by hospital-acquired disability (HAD) and subsequently poor health-related quality of life (HRQOL). While frailty has been shown to be a risk factor, it has yet to be studied as a therapeutic target to improve outcomes. OBJECTIVES: This trial sought to determine the effects of an in-hospital multicomponent intervention targeting physical weakness, cognitive impairment, malnutrition, and anemia on patient-centered outcomes compared to usual care. METHODS: A single-center parallel-group randomized clinical trial was conducted in older patients with acute CVD and evidence of frailty or pre-frailty as measured by the Essential Frailty Toolset (EFT). Patients were randomized to usual care or a multicomponent intervention. Outcomes were HRQOL (EQ-5D-5L score) and disability (Older Americans Resources and Services score) at 30 days post-discharge and mood disturbances (Hospital Anxiety and Depression Scale) at discharge. RESULTS: The trial cohort consisted of 142 patients with a mean age of 79.5 years and 55% females. The primary diagnosis was heart failure in 29%, valvular heart disease in 28%, ischemic heart disease in 14%, arrhythmia in 11%, and other CVDs in 18%. The intervention improved HRQOL scores (coefficient 0.08; 95% CI 0.01, 0.15; p = 0.03) and mood scores (coefficient -1.95; 95% CI -3.82, -0.09; p = 0.04) but not disability scores (coefficient 0.18; 95% CI -1.44, 1.81; p = 0.82). There were no intervention-related adverse events. CONCLUSION: In frail older patients hospitalized for acute CVDs, an in-hospital multicomponent intervention targeted to frailty was safe and led to modest yet clinically meaningful improvements in HRQOL and mental well-being. The downstream impact of these effects on event-free survival and functional status remains to be evaluated in future research, as does the generalizability to other healthcare systems. CLINICAL REGISTRATION NUMBER: NCT04291690.

De-frailing intervention for hospitalized cardiovascular patients in the TARGET-EFT randomized clinical trial.

AIMS: Frailty is disproportionately prevalent in cardiovascular disease patients and exacerbated during hospital admissions, heightening the risk for adverse events and functional decline. Using the Essential Frailty Toolset (EFT) to target physical weakness, cognitive impairment, malnourishment, and anaemia, we tested a multicomponent targeted intervention to de-frail older adults with acute cardiovascular conditions during their hospital admission. METHODS AND RESULTS: The TARGET-EFT trial was a single-center randomized clinical trial at the Jewish General Hospital, Montreal, Canada. We compared a multicomponent de-frailing intervention with usual clinical care. Intervention group patients received exercise, cognitive stimulation, protein supplementation, and iron replacement, as required. In this study, the primary outcome was frailty, as assessed by the SPPB score (Short Physical Performance Battery) at discharge, and the secondary outcome was the SARC-F score (Strength, Assistance walking, Rising from chair, Climbing, Falls) assessed 30 days later. The analysis consisted of 135 patients (mean age of 79.3 years; 54% female) who survived and completed the frailty assessments.Compared with control patients, intervention group patients had a 1.52-point superior SPPB score and a 0.74-point superior SARC-F score. Subgroup analysis suggested that patients with low left ventricular ejection fraction may have attenuated benefits, and that patients who underwent invasive cardiac procedures had the greatest benefits from the intervention. CONCLUSION: We achieved our objective of de-frailing older cardiac inpatients on a short-term basis by improving their physical performance and functioning using a pragmatic multicomponent intervention. This could have positive impacts on their clinical outcomes and ability to maintain independent living in the future. ONE SENTENCE SUMMARY: The multicomponent intervention targeted to the deficits of vulnerable older adults hospitalized with acute cardiovascular diseases successfully de-frailed them on a short-term basis, which can have positive implications on their post-discharge health outcomes.

Echocardiographic assessment and clinical implication of functional tricuspid regurgitation in heart failure with reduced or preserved ejection fraction (ECLIPSE-HF) : Rationale and design of the study.

PURPOSE: Functional tricuspid regurgitation (FTR) has been shown to be associated with increased morbidity and mortality in several clinical conditions, including heart failure (HF) with reduced left ventricular ejection fraction as well as pulmonary arterial hypertension (PAH). We have designed a study aiming at: characterizing the echocardiographic morphology of the tricuspid valve apparatus and the pathophysiology of FTR in heart failure with reduced, mid-range or preserved left ventricular ejection fraction (HFrEF, HFmrEF, HFpEF) and in PAH patients; correlating the morphologic characteristics of tricuspid valve apparatus with hemodynamic severity of FTR; correlating the severity of FTR with the clinical condition and outcome. METHODS: The study will be a non-interventional, prospective, international, multicenter, longitudinal study (ClinicalTrials.gov Identifier NCT05209919). The minimum number of patients which are expected to be enrolled is 300 HF patients, including HFrEF, HFmrEF and HFpEF patients, whereas 100 PAH patients will serve as control. The patients will be enrolled in 20 centers in Europe, North America and Saudi Arabia. Standard echocardiographic parameters will be analyzed by local investigators; strain measurements will be performed in a single central core-lab. CONCLUSIONS: This study has been designed to improve our understanding of pathophysiological mechanisms and clinical relevance of FTR across all HF phenotypes. The results could potentially allow a more appropriate selection of heart failure patients with FTR for tricuspid valve intervention by percutaneous or surgical repair or replacement.

Advances in Multimodality Imaging in Cardio-Oncology: JACC State-of-the-Art Review.

The population of patients with cancer is rapidly expanding, and the diagnosis and monitoring of cardiovascular complications greatly rely on imaging. Numerous advances in the field of cardio-oncology and imaging have occurred in recent years. This review presents updated and practical approaches for multimodality cardiovascular imaging in the cardio-oncology patient and provides recommendations for imaging to detect the myriad of adverse cardiovascular effects associated with antineoplastic therapy, such as cardiomyopathy, atherosclerosis, vascular toxicity, myocarditis, valve disease, and cardiac masses. Uniquely, we address the role of cardiovascular imaging in patients with pre-existing cardiomyopathy, pregnant patients, long-term survivors, and populations with limited resources. We also address future avenues of investigation and opportunities for artificial intelligence applications in cardio-oncology imaging. This review provides a uniform practical approach to cardiovascular imaging for patients with cancer.

Right Heart Chambers Longitudinal Strain Provides Enhanced Diagnosis and Categorization in Patients With Pulmonary Hypertension.

Background: Increased systolic pulmonary arterial pressure (sPAP) could lead to the mechanical dysfunction and myocardial fibrosis of the right heart chambers. Echocardiographic strain analysis has not been adequately studied in patients with pulmonary hypertension (PH). Study design and methods: A cross-sectional cohort of patients with suspected PH and echocardiographic strain evaluation was recruited. The cut-off values of peak tricuspid regurgitation velocity (TRV) with the low probability of PH (≤2.8 m/s), intermediate probability (2.9-3.4 m/s, without other echo PH signs), and high probability of PH (2.9-3.4 m/s with other echo PH signs and >3.4 m/s) categories were studied by right ventricular and right atrial (RA) strain analysis in a sample of 236 patients. Results: The results showed that 58 (56.9%) patients had low, 15 (14.7%) had intermediate, and 29 (28.4%) had a high probability of PH. We observed a negative association between right ventricular free wall strain (RV-FWS) and atrial global strain with sPAP. With the increase in PH severity, RA reservoir, conduit, and contraction (booster) strain values decreased. The identified cut-off values of strain parameters had an adequate ability to detect PH severity categories. In addition, the post-mortem biopsies of right heart chambers from subjects with known severe PH were analyzed to quantify myocardial fibrosis. Our sample of right heart biopsies (n = 12) demonstrated an association between increased sPAP before death and right ventricular and RA fibrosis. Conclusion: Mechanical dysfunction and fibrosis in the right chambers are associated with increased sPAP. Right ventricular and atrial strain could provide enhancement in the diagnosis and categorization of subjects with suspected PH.

Right Heart Pulmonary Circulation Unit Response to Exercise in Patients with Controlled Systemic Arterial Hypertension: Insights from the RIGHT Heart International NETwork (RIGHT-NET).

BACKGROUND: Systemic arterial hypertension (HTN) is the main risk factor for the development of heart failure with preserved ejection fraction (HFpEF). The aim of the study was was to assess the trends in PASP, E/E' and TAPSE during exercise Doppler echocardiography (EDE) in hypertensive (HTN) patients vs. healthy subjects stratified by age. METHODS: EDE was performed in 155 hypertensive patients and in 145 healthy subjects (mean age 62 ± 12.0 vs. 54 ± 14.9 years respectively, p < 0.0001). EDE was undertaken on a semi-recumbent cycle ergometer with load increasing by 25 watts every 2 min. Left ventricular (LV) and right ventricular (RV) dimensions, function and hemodynamics were evaluated. RESULTS: Echo-Doppler parameters of LV and RV function were lower, both at rest and at peak exercise in hypertensives, while pulmonary hemodynamics were higher as compared to healthy subjects. The entire cohort was then divided into tertiles of age: at rest, no significant differences were recorded for each age group between hypertensives and normotensives except for E/E' that was higher in hypertensives. At peak exercise, hypertensives had higher pulmonary artery systolic pressure (PASP) and E/E' but lower tricuspid annular plane systolic excursion (TAPSE) as age increased, compared to normotensives. Differences in E/E' and TAPSE between the 2 groups at peak exercise were explained by the interaction between HTN and age even after adjustment for baseline values (p < 0.001 for E/E', p = 0.011 for TAPSE). At peak exercise, the oldest group of hypertensive patients had a mean E/E' of 13.0, suggesting a significant increase in LV diastolic pressure combined with increased PASP. CONCLUSION: Age and HTN have a synergic negative effect on E/E' and TAPSE at peak exercise in hypertensive subjects.

Prognostic Value of Handgrip Strength in Older Adults Undergoing Cardiac Surgery.

BACKGROUND: Although multidimensional frailty scales have been proven to predict mortality and morbidity in cardiac surgery, there is a need for rapid tools that could be easily administered at the point of care. Handgrip strength (HGS) is an attractive option that can be measured in acutely ill and bed-bound patients, although it has yet to be validated in a large cardiac surgery cohort. METHODS: This is a post hoc analysis of a multicentre prospective study in older patients undergoing coronary artery bypass grafting and/or valve surgery from 2011 to 2019. HGS was measured before surgery and classified by sex-stratified cutoffs. The primary outcome was 1-year mortality and secondary outcomes were 30-day mortality, discharge disposition, and prolonged length of stay. RESULTS: There were 1245 patients included in the analysis (mean age 74.0 ± 6.6 years; 30% female). Weak HGS was associated with advanced age, heart failure, kidney disease, malnutrition, and various frailty scales. In those with weak vs normal HGS, respectively, 1-year mortality was 17% vs 6%, 30-day mortality was 10% vs 3%, prolonged length of stay was 34% vs 19%, and discharge to a health care facility was 45% vs 26% (all P < 0.001). After adjustment, HGS was predictive of 1-year and 30-day mortalities, with odds ratios of 2.44 (95% confidence interval [CI] 1.39-4.29) and 2.83 (1.38-5.81), respectively. HGS cutoffs of < 26 kg in men and < 16 kg in women had the highest predictive performance. CONCLUSIONS: HGS is a simple and effective tool to identify patients at higher risk of mortality and protracted recovery after cardiac surgery.

Age-changes in right ventricular function-pulmonary circulation coupling: from pediatric to adult stage in 1899 healthy subjects. The RIGHT Heart International NETwork (RIGHT-NET).

The present study analyzes age-specific changes in RV function and RV-PA coupling in a large cohort of apparently healthy subjects with a wide age-range, to identify reference values and to study the influence of clinical and echocardiographic cofactors. 1899 Consecutive healthy subjects underwent a standardized transthoracic echocardiographic examination. Tricuspid annular plane systolic excursion (TAPSE) and systolic pulmonary artery pressure (SPAP) were measured. Ventriculo-arterial coupling was then inferred from the TAPSE/SPAP ratio. A quantile regression analysis was used to estimate quantiles 0.05, 0.10, 0.50 (median), 0.90, and 0.95 of TAPSE, SPAP and TAPSE/SPAP. The association between age and each of these values was determined. The mean age of the group was 45.2 ± 18.5 years (range 1 to 102 years), 971 were males. SPAP increased with age, whereas TAPSE and TAPSE/SPAP ratio decreased. Upon multivariate modeling, the most significant positive associations for TAPSE were body surface area (BSA) driven by the pediatric group, stroke volume (SV), E/A and negatively heart rate and E/e' ratio. SPAP was positively associated with increasing age, SV, E/A, E/e' and negatively with BSA. TAPSE/SPAP ratio was negatively associated with age, female sex, and E/e' and positively with BSA. A preserved relationship between TAPSE and SPAP was found across the different age groups. TAPSE, SPAP and TAPSE/SPAP demonstrate important trends and associations with advancing age, impaired diastolic function, affected by female sex and BSA However the relationship between TAPSE and SPAP is relatively well preserved across the age spectrum.

The role of echocardiography in amniotic fluid embolism: a case series and review of the literature.

PURPOSE: Amniotic fluid embolism (AFE) is a rare, but often fatal condition characterized by sudden hemodynamic instability and coagulopathy occurring during labour or in the early postpartum period. As the mechanisms leading to shock and the cardiovascular effects of AFE are incompletely understood, the purpose of this case series is to describe how AFE presents on echocardiography and review limited reports in the literature. CLINICAL FEATURES: We describe three cases of AFE at the Jewish General Hospital, a tertiary care centre in Montreal, Canada. All cases met the Clark diagnostic criteria, which comprise 1) sudden cardiorespiratory arrest or both hypotension and respiratory compromise, 2) disseminated intravascular coagulation, 3) clinical onset during labour or within 30 min of delivery of the placenta, and 4) absence of fever. Two patients had a cardiac arrest and the third developed significant hypotension and hypoxia. In all patients, point-of-care echocardiography at the time of shock revealed signs of right ventricular failure including a D-shaped septum, acute pulmonary hypertension, and right ventricular systolic dysfunction. CONCLUSION: This case series and literature review of AFE emphasizes the importance of echocardiography in elucidating the etiology of maternal shock. The presence of right ventricular failure may be considered an important criterion to diagnose AFE.

RéSUMé: OBJECTIF: L'embolie de liquide amniotique (ELA) est une complication rare mais souvent fatale caractérisée par une instabilité hémodynamique et une coagulopathie soudaines survenant pendant le travail obstétrical ou au début de la période postpartum. Étant donné que les mécanismes menant au choc et les effets cardiovasculaires de l'ELA ne sont que partiellement compris, le but de cette série de cas était de décrire comment l'ELA apparaît à l'échocardiographie et de passer en revue les rares comptes rendus dans la littérature. CARACTéRISTIQUES CLINIQUES: Nous décrivons trois cas d'ELA survenus à l'Hôpital général juif, un centre tertiaire de soins à Montréal, au Canada. Tous les cas remplissaient les critères diagnostiques de Clark, qui comportent 1) un arrêt cardiorespiratoire soudain ou une hypotension accompagnée d'une détresse respiratoire, 2) une coagulation intravasculaire disséminée, 3) une apparition clinique pendant le travail obstétrical ou dans un délai de 30 minutes suivant la délivrance du placenta, et 4) l'absence de fièvre. Deux patientes ont subi un arrêt cardiaque et le tiers des patientes ont manifesté une hypotension et une hypoxie significatives. Chez toutes les patientes, l'échocardiographie au chevet au moment du choc a révélé des signes d'insuffisance ventriculaire droite, y compris un septum en forme de D, une hypertension pulmonaire aiguë et une dysfonction systolique ventriculaire droite. CONCLUSION: Cette série de cas et revue de littérature de l'ELA souligne l'importance de l'échocardiographie pour élucider l'étiologie du choc maternel. La présence d'une insuffisance ventriculaire droite peut être considérée un critère important pour diagnostiquer une ELA.

The Essential Frailty Toolset in Older Adults Undergoing Coronary Artery Bypass Surgery.

Background The Essential Frailty Toolset (EFT) was shown to be easy to use and predictive of adverse events in patients undergoing aortic valve replacement procedures. The objective of this study was to evaluate the EFT in patients undergoing coronary artery bypass grafting procedures. Methods and Results The McGill Frailty Registry prospectively included patients ≥60 years of age undergoing urgent or elective isolated coronary artery bypass grafting between 2011 and 2018 at 2 hospitals. The preoperative EFT was scored 0 to 5 points as a function of timed chair rises, Mini-Mental Status Examination, serum albumin, and hemoglobin. The primary outcome was all-cause mortality assessed by Cox proportional hazards regression. The cohort consisted of 500 patients with a mean age of 71.4 ± 6.4 years, of which 27% presented with acute coronary syndromes requiring urgent surgery. The mean EFT was 1.3 ± 1.1 points, 132 (26%) were nonfrail, 298 (60%) were prefrail, and 70 (14%) were frail. Over a median follow-up of 4.0 years, 78 deaths were observed. In nonfrail, prefrail, and frail patients, survival at 1 year was 98%, 95%, and 91%, and at 5 years was 89%, 83%, and 63% (P<0.001). After adjustment, each incremental EFT point was associated with a hazard ratio of 1.28 (95% CI, 1.05-1.56) and frail patients had a 3-fold increase in all-cause mortality. Conclusions The EFT is a pragmatic and highly prognostic tool to assess frailty and guide decisions for coronary artery bypass grafting in older adults. Furthermore, the EFT may be actionable through targeted interventions such as cardiac rehabilitation and nutritional optimization.

Sarcopenia in cardiac surgery: Dual X-ray absorptiometry study from the McGill frailty registry.

BACKGROUND: To determine the prevalence and prognostic value of sarcopenia measured by dual x-ray absorptiometry (DXA) and physical performance tests in patients undergoing coronary artery bypass surgery or heart valve procedures. METHODS: Adults undergoing cardiac surgery were prospectively enrolled and completed a questionnaire, physical performance battery, and a DXA scan (GE Lunar) to measure appendicular muscle mass indexed to height2 (AMMI). Patients were categorized as sarcopenic based on European Working Group 2 guidelines if they had low AMMI defined as <7 kg/m2 for men or <5.5 kg/m2 for women, and low muscle strength defined as 5 chair rise time ≥15 seconds. Cox proportional hazards regression was used to test the association between sarcopenia and all-cause mortality over a median follow-up of 4.3 years. RESULTS: The cohort consisted of 141 patients with a mean age of 69.7 ± 10.0 years and 21% females. The prevalence rates of low AMMI, slow chair rise time, and sarcopenia (low AMMI and slow chair rise time) were 24%, 57%, 13%, respectively. The 4-year survival rate was 79% in the non-sarcopenic group as compared to 56% in the sarcopenic group (Log-rank P = 0.01). In the multivariable model, each standard deviation of decreasing AMMI and increasing chair rise time was associated with a hazard ratio for all-cause mortality of 1.84 (95% CI 1.18, 2.86) and 1.79 (95% CI 1.26, 2.54), respectively. CONCLUSION: Lower-extremity muscle strength and DXA-based muscle mass are objective indicators of sarcopenia that are independently predictive of all-cause mortality in older cardiac surgery patients.

Feasibility of semi-recumbent bicycle exercise Doppler echocardiography for the evaluation of the right heart and pulmonary circulation unit in different clinical conditions: the RIGHT heart international NETwork (RIGHT-NET).

Exercise Doppler echocardiography (EDE) is a well-validated tool in ischemic and valvular heart diseases. However, its use in the assessment of the right heart and pulmonary circulation unit (RH-PCU) is limited. The aim of this study is to assess the semi-recumbent bicycle EDE feasibility for the evaluation of RH-PCU in a large multi-center population, from healthy individuals and elite athletes to patients with overt or at risk of developing pulmonary hypertension (PH). From January 2019 to July 2019, 954 subjects [mean age 54.2 ± 16.4 years, range 16-96, 430 women] underwent standardized semi-recumbent bicycle EDE with an incremental workload of 25 watts every 2 min, were prospectively enrolled among 7 centers participating to the RIGHT Heart International NETwork (RIGHT-NET). EDE parameters of right heart structure, function and pressures were obtained according to current recommendations. Right ventricular (RV) function at peak exercise was feasible in 903/940 (96%) by tricuspid annular plane systolic excursion (TAPSE), 667/751 (89%) by tissue Doppler-derived tricuspid lateral annular systolic velocity (S') and 445/672 (66.2%) by right ventricular fractional area change (RVFAC). RV-right atrial pressure gradient [RV-RA gradient = 4 × tricuspid regurgitation velocity2 (TRV)] was feasible in 894/954 patients (93.7%) at rest and in 816/954 (85.5%) at peak exercise. The feasibility rate in estimating pulmonary artery pressure improved to more than 95%, if both TRV and/or right ventricular outflow tract acceleration time (RVOT AcT) were considered. In high specialized echocardiography laboratories semi-recumbent bicycle EDE is a feasible tool for the assessment of the RH-PCU pressure and function.

A multicentric quality-control study of exercise Doppler echocardiography of the right heart and the pulmonary circulation. The RIGHT Heart International NETwork (RIGHT-NET).

PURPOSE: This study was a quality-control study of resting and exercise Doppler echocardiography (EDE) variables measured by 19 echocardiography laboratories with proven experience participating in the RIGHT Heart International NETwork. METHODS: All participating investigators reported the requested variables from ten randomly selected exercise stress tests. Intraclass correlation coefficients (ICC) were calculated to evaluate the inter-observer agreement with the core laboratory. Inter-observer variability of resting and peak exercise tricuspid regurgitation velocity (TRV), right ventricular outflow tract acceleration time (RVOT Act), tricuspid annular plane systolic excursion (TAPSE), tissue Doppler tricuspid lateral annular systolic velocity (S'), right ventricular fractional area change (RV FAC), left ventricular outflow tract velocity time integral (LVOT VTI), mitral inflow pulsed wave Doppler velocity (E), diastolic mitral annular velocity by TDI (e') and left ventricular ejection fraction (LVEF) were measured. RESULTS: The accuracy of 19 investigators for all variables ranged from 99.7 to 100%. ICC was > 0.90 for all observers. Inter-observer variability for resting and exercise variables was for TRV = 3.8 to 2.4%, E = 5.7 to 8.3%, e' = 6 to 6.5%, RVOT Act = 9.7 to 12, LVOT VTI = 7.4 to 9.6%, S' = 2.9 to 2.9% and TAPSE = 5.3 to 8%. Moderate inter-observer variability was found for resting and peak exercise RV FAC (15 to 16%). LVEF revealed lower resting and peak exercise variability of 7.6 and 9%. CONCLUSIONS: When performed in expert centers EDE is a reproducible tool for the assessment of the right heart and the pulmonary circulation.

Muscle Mass and Direct Oral Anticoagulant Activity in Older Adults With Atrial Fibrillation.

BACKGROUND: Direct oral anticoagulants (DOAC) are hydrophilic drugs with plasma levels inversely proportional to lean body mass. Sarcopenic patients with low muscle mass may be at risk for supra-therapeutic DOAC levels and bleeding complications. We therefore sought to examine the influence of lean body mass on DOAC levels in older adults with atrial fibrillation (AF). METHODS: A prospective cohort study was conducted with patients 65 years of age or more receiving rivaroxaban or apixaban for AF. Appendicular lean mass (ALM) was measured using a bioimpedance device and a dual X-ray absorptiometry scanner. DOAC levels were measured using a standardized anti-Xa assay 4 hours after (peak) and 1 hour before (trough) ingestion. RESULTS: The cohort consisted of 62 patients (47% female, 77.0 ± 6.1 years). The prescribed DOACs were apixaban 2.5 mg (21%), apixaban 5 mg (53%), and rivaroxaban 20 mg (26%). Overall, 16% had supra-therapeutic DOAC levels at trough and 25% at peak. In the multivariable logistic regression model, lower ALM was independently associated with supra-therapeutic DOAC levels at trough (odds ratio per ↓ 1-kg 1.23, 95% confidence interval 1.02 to 1.49) and peak (odds ratio per ↓ 1-kg 1.18, 95% confidence interval 1.02 to 1.37). Addition of ALM to a model consisting of age, total body weight, and renal function resulted in improved discrimination for supra-therapeutic DOAC levels. CONCLUSION: Our proof-of-concept study has identified an association between ALM and DOAC levels in older adults with AF. Further research is needed to determine the impact of ALM on bleeding complications and the potential role of ALM-guided dosing for sarcopenic patients.

Cardiovascular Care of the Oncology Patient During COVID-19: An Expert Consensus Document From the ACC Cardio-Oncology and Imaging Councils.

In response to the coronavirus disease 2019 (COVID-19) pandemic, the Cardio-Oncology and Imaging Councils of the American College of Cardiology offers recommendations to clinicians regarding the cardiovascular care of cardio-oncology patients in this expert consensus statement. Cardio-oncology patients-individuals with an active or prior cancer history and with or at risk of cardiovascular disease-are a rapidly growing population who are at increased risk of infection, and experiencing severe and/or lethal complications by COVID-19. Recommendations for optimizing screening and monitoring visits to detect cardiac dysfunction are discussed. In addition, judicious use of multimodality imaging and biomarkers are proposed to identify myocardial, valvular, vascular, and pericardial involvement in cancer patients. The difficulties of diagnosing the etiology of cardiovascular complications in patients with cancer and COVID-19 are outlined, along with weighing the advantages against risks of exposure, with the modification of existing cardiovascular treatments and cardiotoxicity surveillance in patients with cancer during the COVID-19 pandemic.