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.

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.

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.

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.

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.

Phase Angle as a Biomarker for Frailty and Postoperative Mortality: The BICS Study.

Background Phase angle (PA) is a bioimpedance measurement that is determined lean body mass and hydration status. Patients with low PA values are more likely to be frail, sarcopenic, or malnourished. Previous work has shown that low PA predicts adverse outcomes after cardiac surgery, but the effect of PA on survival has not previously been assessed in this setting. Methods and Results The BICS (Bioimpedance in Cardiac Surgery) study recruited 277 patients undergoing major cardiac surgery at 2 university-affiliated hospitals in Montreal, QC, Canada. Bioimpedance measurements as well as frailty and nutritional assessments were performed preoperatively. The primary outcome was all-cause mortality. Secondary outcomes were 30-day mortality, postoperative morbidity, and hospital length of stay. There were 10 deaths at 1 month of follow-up and 16 deaths at 12 months of follow-up. PA was associated with age, sex, body mass index, comorbidities, and frailty, as measured by the Short Physical Performance Battery and Fried scales. After adjusting for Society of Thoracic Surgeons-predicted mortality, lower PA was associated with higher mortality at 1 month (adjusted odds ratio, 3.57 per 1° decrease in PA ; 95% confidence interval, 1.35-9.47) and at 12 months (adjusted odds ratio, 3.03 per 1° decrease in PA ; 95% confidence interval, 1.30-7.09), a higher risk of overall morbidity (adjusted hazard ratio, 2.51 per 1° decrease in PA ; 95% confidence interval, 1.32-4.75), and a longer hospital length of stay (adjusted ß, 4.8 days per 1° decrease in PA ; 95% confidence interval, 1.3-8.2 days). Conclusions Low PA is associated with frailty and is predictive of mortality, morbidity, and length of stay after major cardiac surgery. Further work is needed to determine the responsiveness of PA to interventions aimed at reversing frailty.

Cost of Cardiac Surgery in Frail Compared With Nonfrail Older Adults.

BACKGROUND: Frailty is a risk factor for mortality, morbidity, and prolonged length of stay after cardiac surgery, all of which are major drivers of hospitalization costs. The incremental hospitalization costs incurred in frail patients have yet to be elucidated. METHODS: Patients aged ≥ 60 years were evaluated for frailty before coronary artery bypass grafting or heart valve surgery at 2 academic centres between 2013 and 2015 as part of the McGill Frailty Registry. Total costs were summed from the date of the index surgery to the date of hospital discharge. Mutivariable linear regression was used to determine the association between preoperative frailty status and total costs after adjusting for conventional surgical risk factors. RESULTS: Among 235 patients included in the analysis, the median age was 73.0 years (interquartile range [IQR], 70.0-78.0 years) and 68 (29%) were women. The median cost was $32,742 (IQR, $23,221-$49,627) in 91 frail patients compared with $23,370 (IQR, $19,977-$29,705) in 144 nonfrail patients. Seven extreme-cost cases > $100,000 were identified, and all of the patients in these cases exhibited baseline frailty. In the multivariable model, total costs were independently associated with frailty (adjusted additional cost, $21,245; 95% confidence interval [CI], $12,418-$30,073; P < 0.001) and valve surgery (adjusted additional cost, $20,600; 95% CI, $9,661-$31,539; P < 0.001). CONCLUSIONS: Frailty is associated with a marked increase in hospitalization costs after cardiac surgery, an effect that persists after adjusting for age, sex, surgery type, and surgical risk score. Further efforts are needed to optimize care and resource use in this vulnerable population.

Frailty in Older Adults Undergoing Aortic Valve Replacement: The FRAILTY-AVR Study.

BACKGROUND: Frailty is a geriatric syndrome that diminishes the potential for functional recovery after a transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) procedure; however, its integration in clinical practice has been limited by a lack of consensus on how to measure it. OBJECTIVES: This study sought to compare the incremental predictive value of 7 different frailty scales to predict poor outcomes following TAVR or SAVR. METHODS: A prospective cohort of older adults undergoing TAVR or SAVR was assembled at 14 centers in 3 countries from 2012 to 2016. The following frailty scales were compared: Fried, Fried+, Rockwood, Short Physical Performance Battery, Bern, Columbia, and the Essential Frailty Toolset (EFT). Outcomes of interest were all-cause mortality and disability 1 year after the procedure. RESULTS: The cohort was composed of 1,020 patients with a median age of 82 years. Depending on the scale used, the prevalence of frailty ranged from 26% to 68%. Frailty as measured by the EFT was the strongest predictor of death at 1 year (adjusted odds ratio [OR]: 3.72; 95% confidence interval [CI]: 2.54 to 5.45) with a C-statistic improvement of 0.071 (p < 0.001) and integrated discrimination improvement of 0.067 (p < 0.001). Moreover, the EFT was the strongest predictor of worsening disability at 1 year (adjusted OR: 2.13; 95% CI: 1.57 to 2.87) and death at 30 days (adjusted OR: 3.29; 95% CI: 1.73 to 6.26). CONCLUSIONS: Frailty is a risk factor for death and disability following TAVR and SAVR. A brief 4-item scale encompassing lower-extremity weakness, cognitive impairment, anemia, and hypoalbuminemia outperformed other frailty scales and is recommended for use in this setting. (Frailty Assessment Before Cardiac Surgery & Transcatheter Interventions; NCT01845207).

Functional and Exercise Limitations After a First Episode of Pulmonary Embolism: Results of the ELOPE Prospective Cohort Study.

BACKGROUND: We aimed to determine the frequency and predictors of exercise limitation after pulmonary embolism (PE) and to assess its association with health-related quality of life (HRQoL) and dyspnea. METHODS: One hundred patients with acute PE were recruited at five Canadian hospitals from 2010 to 2013. Cardiopulmonary exercise testing (CPET) was performed at 1 and 12 months. Quality of life (QoL), dyspnea, 6-min walk distance (6MWD), residual clot burden (perfusion scan, CT pulmonary angiography), cardiac function (echocardiography), and pulmonary function tests (PFTs) were measured during follow-up. The prespecified primary outcome was percent predicted peak oxygen uptake (Vo2 peak) < 80% at 1-year CPET. RESULTS: At 1 year, 40 of 86 patients (46.5%) had percent predicted Vo2 peak < 80% on CPET, which was associated with significantly worse generic health-related QoL (HRQoL), PE-specific HRQoL and dyspnea scores, and significantly reduced 6MWD at 1 year. Predictors of the primary outcome included male sex (relative risk [RR], 3.2; 95% CI, 1.3-8.1), age (RR, 0.98; 95% CI, 0.96-0.99 per 1-year age increase), BMI (RR 1.1; 95% CI, 1.01-1.2 per 1 kg/m2 BMI increase), and smoking history (RR, 1.8; 95% CI, 1.1-2.9), as well as percent predicted Vo2 peak < 80% on CPET at 1 month (RR, 3.8; 95% CI,1.9-7.2), and 6MWD at 1 month (RR, 0.82; 95% CI, 0.7-0.9 per 30-m increased walking distance). Baseline or residual clot burden was not associated with the primary outcome. Mean PFT and echocardiographic results (pulmonary artery pressure, right and left ventricular systolic function) at 1 year were similarly within normal limits in both patients with exercise limitations and those without such limitations. CONCLUSIONS: Almost half of patients with PE have exercise limitation at 1 year that adversely influences HRQoL, dyspnea, and walking distance. CPET or 6MWD testing at 1 month may help to identify patients with a higher risk of exercise limitation at 1 year after PE. Based on our results, we believe that the deconditioning that occurs after acute PE could underlie this exercise limitation, but we cannot exclude the fact that this may have been present before PE. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01174628; URL: www.clinicaltrials.gov.

Derivation and Validation of Prognosis-Based Age Cutoffs to Define Elderly in Cardiac Surgery.

BACKGROUND: The age cutoff to define elderly is controversial in cardiac surgery, empirically ranging from ≥65 to ≥80 years. Beyond semantics, this has important implications as a starting point for clinical care pathways and inclusion in trials. We sought to characterize the relationship between age and adverse outcomes in patients undergoing cardiac surgery and to derive and validate prognosis-based age cutoffs. METHODS AND RESULTS: Six thousand five hundred seventy one consecutive adult patients undergoing cardiac surgery at 3 hospitals in the United States and Canada were included in the cohort. Logistic regression models and generalized additive models with thin-plate splines were fit to the data. The age distribution was 50 to 59 years in 1244 (18.9%), 60 to 69 years in 2144 (32.6%), 70 to 79 years in 2000 (30.4%), ≥80 years in 1183 (18.0%) patients. After controlling for sex and type of operation, the relationship between age and 30-day operative mortality was found to be nonlinear. Receiver operating characteristic analysis showed that the optimal cutoffs to identify older patients at higher risk of operative mortality were greater than 74, 78, and 75 years for isolated coronary bypass, isolated valve surgery, and coronary bypass plus valve surgery, respectively. These age cutoffs were validated in an independent cohort. CONCLUSIONS: The relationship between age and operative mortality is not linear, manifesting a steeper rise after age 75 for coronary bypass and approaching octogenarian age for isolated valve surgery. Rather than using arbitrary age cutoffs to define elderly, the outcomes-based cutoff of ≥75 years should be used to identify the population of older adults that has higher risk and may benefit from preoperative geriatric evaluation and optimization.

Tricuspid Regurgitation: 2015 Reflections and Re-evaluation.

OPINION STATEMENT: The tricuspid valve is, in fact, anatomically and functionally more complex than its left-sided counterpart-the mitral valve. Patients may develop tricuspid regurgitation from a variety of mechanisms. While current guidelines provide a very basic approach to tricuspid regurgitation (TR) evaluation, more recent techniques, particularly 3D echocardiography, have provided novel insights into how we can ascertain the mechanism and severity of tricuspid regurgitation, how the tricuspid valve adapts to disease and, importantly, how we assess the effects of TR on right ventricular size and function. We anticipate that these advances will soon yield dividends that will help us decide on approaches to treatment and timing of surgery.

Usefulness of right ventricular dysfunction to predict new-onset atrial fibrillation following coronary artery bypass grafting.

Postoperative atrial fibrillation (AF) is a serious yet common complication after coronary artery bypass grafting (CABG) surgery. Risk factors for postoperative AF have been identified, including echocardiographic parameters, and these are relied on to implement preventative strategies that reduce the incidence of AF. There has yet to be a study examining the impact of echocardiographic right-sided cardiac parameters on the prediction of postoperative AF. Thus, a panel of right-sided cardiac parameters was measured in a cohort of patients undergoing isolated CABG surgery, excluding those who did not have echocardiographic assessment within 30 days before surgery and those with any history of AF. The primary outcome was postoperative AF defined as any episode of AF requiring treatment during the index hospitalization. Postoperative AF occurred in 197 of 768 patients (25.6%); these were older and more likely to have hypertension and chronic kidney disease. After adjustment for clinical and echocardiographic variables, left atrial volume index ≥34 ml/m(2) (odds ratio [OR] 1.98, 95% confidence interval [CI] 1.36 to 2.87), abnormal right ventricular myocardial performance index (OR 1.50, 95% CI 1.01 to 2.24), and advancing age (OR 1.05, 95% CI 1.03 to 1.07) were found to be independent predictors of postoperative AF. In conclusion, right ventricular myocardial performance index is a novel predictor of postoperative AF in patients undergoing isolated CABG surgery and appears to be additive to established risk factors such as age and left atrial volume.

Incremental value of the preoperative echocardiogram to predict mortality and major morbidity in coronary artery bypass surgery.

BACKGROUND: Although echocardiography is commonly performed before coronary artery bypass surgery, there has yet to be a study examining the incremental prognostic value of a complete echocardiogram. METHODS AND RESULTS: Patients undergoing isolated coronary artery bypass surgery at 2 hospitals were divided into derivation and validation cohorts. A panel of quantitative echocardiographic parameters was measured. Clinical variables were extracted from the Society of Thoracic Surgeons database. The primary outcome was in-hospital mortality or major morbidity, and the secondary outcome was long-term all-cause mortality. The derivation cohort consisted of 667 patients with a mean age of 67.2±11.1 years and 22.8% females. The following echocardiographic parameters were found to be optimal predictors of mortality or major morbidity: severe diastolic dysfunction, as evidenced by restrictive filling (odds ratio, 2.96; 95% confidence interval, 1.59-5.49), right ventricular dysfunction, as evidenced by fractional area change <35% (odds ratio, 3.03; 95% confidence interval, 1.28-7.20), or myocardial performance index >0.40 (odds ratio, 1.89; 95% confidence interval, 1.13-3.15). These results were confirmed in the validation cohort of 187 patients. When added to the Society of Thoracic Surgeons risk score, the echocardiographic parameters resulted in a net improvement in model discrimination and reclassification with a change in c-statistic from 0.68 to 0.73 and an integrated discrimination improvement of 5.9% (95% confidence interval, 2.8%-8.9%). In the Cox proportional hazards model, right ventricular dysfunction and pulmonary hypertension were independently predictive of mortality over 3.2 years of follow-up. CONCLUSIONS: Preoperative echocardiography, in particular right ventricular dysfunction and restrictive left ventricular filling, provides incremental prognostic value in identifying patients at higher risk of mortality or major morbidity after coronary artery bypass surgery.

Timing of bypass surgery in stable patients after acute myocardial infarction.

OBJECTIVES: To determine the optimal timing for bypass surgery in stable patients after acute myocardial infarction (MI). BACKGROUND: Coronary artery bypass graft surgery (CABG) is a proven treatment for coronary artery disease. Because of the hypothesized risk of hemorrhagic transformation, it had become common practice to wait four to six weeks after MI. Recently, improvements in surgical and perioperative management, as well as an increase in pre-CABG in-hospital waiting times and excess burden on health care resources, have pushed surgeons to operate earlier. The optimal timing for a stable patient to undergo CABG after MI is unclear, because there have been no randomized trials to answer this question. METHODS: The published literature comparing early versus late surgical revascularization procedures in stable post-MI patients was reviewed. RESULTS: No randomized, prospective trials were found; however, several retrospective studies were identified. Most series examining Q wave MIs showed that mortality is higher in the early stages post-MI and progressively decreases with time post-MI. When studies examined non-Q wave MIs separately, there appeared to be less of a mortality difference between early and late surgical revascularization. There was a large disparity between the definitions of early surgery post-MI among the studies, some as early as 6 h and others up to eight days. Factors that increased mortality include abnormal left ventricular function and urgency of surgery, and some studies found risk models helpful to define increased risk after infarction. The possible increased risk of early surgery may be balanced against the potential for improved remodelling, improved quality of life and decreased hospital stay costs. CONCLUSIONS: There is a need for a randomized, prospective trial examining the optimal timing for CABG in stable post-MI patients.

Clinical outcome and echocardiographic predictors of aortic valve replacement in patients with bicuspid aortic valve.

BACKGROUND: Clinical outcomes and echocardiographic parameters associated with aortic valve replacement (AVR) for bicuspid aortic valve are scarce. METHODS: We conducted retrospective analysis of 208 adults with bicuspid aortic valve referred for transthoracic echocardiograms. RESULTS: The Kaplan-Meier survival free of death or need for cardiac surgery was 72% at 5 years. Cardiac surgery was performed in 19%, the majority (68%) for symptomatic aortic stenosis. Peak gradient 80 mm Hg or greater (hazard ratio 11.8, 95% confidence interval 3.7-37.8, P < .0001) and aortic valve area less than or equal to 0.75 cm(2) (hazard ratio 2.9, 95% confidence interval 1.0-8.5, P = .05) predicted the need for AVR. Patients with a large (54%) versus normal left ventricular outflow tract dimension underwent AVR for symptomatic aortic stenosis at a larger calculated aortic valve area (1.07 +/- 0.21 vs 0.75 +/- 0.18 cm(2), P < .0001) but at a similar peak gradient and velocity ratio (76 +/- 19 vs 76 +/- 22 mm Hg, P = not significant; 0.23 +/- 0.06 vs 0.26 +/- 0.12, P = not significant, respectively). CONCLUSIONS: Clinical events are common among patients with bicuspid aortic valve. Peak gradient 80 mm Hg or more and aortic valve area less than or equal to 0.75 cm(2) predicts the need for AVR. Gradients and velocity ratio better reflect the hemodynamic burden of aortic stenosis in patients with a large left ventricular outflow tract.