Association Between Functional Tricuspid Regurgitation and Mortality Following Cardiac Surgery.

Background: Current guidelines recommend concomitant repair of certain non-severe cases of tricuspid regurgitation (TR) in patients undergoing cardiac surgery, but the prognostic relevance and postsurgical impact of the TR remain uncertain. Objectives: The purpose of this study was to determine the prognostic impact of functional TR in patients undergoing diverse cardiac surgeries and to examine the effect-modifying role of patient characteristics in patients in whom TR confers a greater risk of adverse outcomes. Methods: Patients undergoing coronary artery bypass, aortic, and mitral valve surgery were included. Patients with severe TR, organic tricuspid valve pathology, undergoing tricuspid valve surgery or without a recent preoperative echocardiogram were excluded. Clinical variables were extracted from the Society of Thoracic Surgeons Adult Cardiac Surgery Database. An independent cohort was used for external validation. Results: Of 2,119 patients (mean age 67.4 years; 29% females), TR severity was moderate in 185 (9%), mild in 636 (30%), trivial in 1,126 (53%), and absent in 172 (8%). There were 238 deaths during the median follow-up period of 2.6 years. After adjusting for relevant factors, moderate TR was found to be independently associated with mid-term mortality (HR: 2.58; 95% CI: 1.22-5.47) and with in-hospital mortality or major morbidity (OR: 3.18; 95% CI: 1.37-7.42). The association between TR and mortality was apparent when preoperative pulmonary artery systolic pressure was <40 mm Hg but not ≥40 mm Hg (P for interaction = 0.036). Conclusions: In this diverse cohort of contemporary cardiac surgery patients, moderate functional TR was associated with increased mortality and major morbidity, particularly in the absence of pulmonary hypertension.

Risk Prediction in Aortic Valve Replacement: Incremental Value of the Preoperative Echocardiogram.

BACKGROUND: Risk prediction is a critical step in patient selection for aortic valve replacement (AVR), yet existing risk scores incorporate very few echocardiographic parameters. We sought to evaluate the incremental predictive value of a complete echocardiogram to identify high-risk surgical candidates before AVR. METHODS AND RESULTS: A cohort of patients with severe aortic stenosis undergoing surgical AVR with or without coronary bypass was assembled at 2 tertiary centers. Preoperative echocardiograms were reviewed by independent observers to quantify chamber size/function and valve function. Patient databases were queried to extract clinical data. The cohort consisted of 432 patients with a mean age of 73.5 years and 38.7% females. Multivariable logistic regression revealed 3 echocardiographic predictors of in-hospital mortality or major morbidity: E/e' ratio reflective of elevated left ventricular (LV) filling pressure; myocardial performance index reflective of right ventricular (RV) dysfunction; and small LV end-diastolic cavity size. Addition of these echocardiographic parameters to the STS risk score led to an integrated discrimination improvement of 4.1% (P<0.0001). After a median follow-up of 2 years, Cox regression revealed 5 echocardiographic predictors of all-cause mortality: small LV end-diastolic cavity size; LV mass index; mitral regurgitation grade; right atrial area index; and mean aortic gradient <40 mm Hg. CONCLUSIONS: Echocardiographic measures of LV diastolic dysfunction and RV performance add incremental value to the STS risk score and should be integrated in prediction when evaluating the risk of AVR. In addition, findings of small hypertrophied LV cavities and/or low mean aortic gradients confer a higher risk of 2-year mortality.

Differential left ventricular outflow tract remodeling and dynamics in aortic stenosis.

BACKGROUND: Left ventricular outflow tract (LVOT) geometry is variable and often elliptical, which can affect aortic valve area calculation in patients with aortic stenosis (AS). Specific differences in LVOT geometry and dynamics between patients with AS and normal control subjects have not been described. The aim of this study was to test the hypothesis that differences in LVOT geometry in patients with AS might relate to variable LVOT remodeling and stiffness relative to normal control subjects. METHODS: In 54 patients with severe AS and 33 control subjects without AS, LVOT geometry, dynamics, remodeling, and stiffness were assessed by three-dimensional transesophageal echocardiography. LVOT stiffness was measured by calculating the distensibility coefficient, defined as the percentage change in LVOT area relative to change in left ventricular pressure. LVOT remodeling was assessed by measuring the posterior LVOT wall thickness. Multivariate linear regression analysis was used to determine independent associations with peak systolic LVOT ellipticity. LVOT area by three-dimensional transesophageal echocardiographic planimetry was compared with areas obtained assuming circular or elliptical geometry. RESULTS: At end-diastole, LVOT geometry was similar between patients with AS and normal control subjects. In patients with AS, however, the percentage change in cross-sectional area (7.5% vs 14.7%, P < .001) from end-diastole to peak systole was lower compared with normal control subjects, while peak systolic ellipticity index was higher in patients with AS (1.18 vs 1.08, P < .001). Compared with control subjects, patients with AS had lower distensibility coefficients (4.7 ± 1.9 × 10(4) vs 12.5 ± 5.3 × 10(4) mm Hg(-1), P < .001) and higher posterior LVOT wall thickness (3.5 ± 0.8 vs 2.3 ± 0.5 mm, P < .001). In multivariate analysis, posterior LVOT wall thickness and distensibility coefficient were independently associated with peak systolic LVOT ellipticity index. LVOT area underestimation by transthoracic echocardiography was higher in patients with AS when assuming circular geometry (20% vs 12%, P = .001). CONCLUSIONS: The LVOT is less distensible and undergoes remodeling in severe AS. These changes lead to greater peak systolic ellipticity and greater LVOT cross-sectional area underestimation relative to normal control subjects. These findings have important implications for the assessment of AS severity.

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.

Brown adipose tissue blood flow and mass in obesity: a contrast ultrasound study in mice.

BACKGROUND: When activated by the sympathetic nervous system, brown adipose tissue (BAT) increases energy expenditure to produce heat. Augmenting BAT mass or increasing BAT activation could potentially be used to decrease obesity. Noninvasive methods to detect and monitor BAT mass are needed. Contrast ultrasound can estimate BAT blood flow and is able to measure the perfused volume of an organ and thus its mass. The objective of this study was to evaluate whether contrast ultrasound could characterize BAT mass in two mouse models of obesity: wild-type mice fed a high-fat diet and mutant db/db mice. METHODS: Contrast ultrasound of BAT (Definity 2 µL/min; 14-MHz linear probe) was performed before and after stimulation of BAT with norepinephrine (NE). BAT replenishment curves were obtained, and blood flow was estimated by the product of the curve's plateau and slope. Additionally, consecutive two-dimensional images of perfused BAT were acquired at 1-mm intervals after stimulation with NE and used to assess BAT volume and mass. RESULTS: BAT blood flow increased after NE infusion in all mice studied. Blood flow response to NE was similar in wild-type mice fed either a low-fat diet or a high-fat diet. BAT blood flow was lower in db/db mice than in wild-type mice (P = .02). Contrast ultrasound-derived BAT mass was correlated with BAT mass obtained at necropsy (R(2) = 0.83, P < .001). BAT mass was higher in mice fed a high-fat diet than in those fed a low-fat diet. CONCLUSIONS: Contrast ultrasound can be used to estimate BAT mass in mice when BAT vascularization is not significantly impaired. This noninvasive technique may potentially allow the serial evaluation of therapies designed to augment BAT mass.

Differential left ventricular remodelling and longitudinal function distinguishes low flow from normal-flow preserved ejection fraction low-gradient severe aortic stenosis.

AIMS: There is uncertainty in identifying patients with severe aortic stenosis (AS) with preserved left ventricular (LV) ejection fraction, low flow, and low gradients (LFLG). Prior studies propose that these patients demonstrate significant concentric remodelling and decreased survival, while others suggest that they have features and survival similar to moderate AS. METHODS AND RESULTS: We compared the clinical characteristics, echocardiographic features, and overall survival of LFLG AS patients (n = 38) to those with normal-flow, low-gradient (NFLG) severe AS (n = 75) and moderate AS (n = 70). Low-flow, low-gradient patients had the lowest end-diastolic volume index (43 vs. 54 vs. 54 mL/m², P < 0.001), highest relative wall thickness (RWT) (60 vs. 49 vs. 48%, P < 0.001), and lowest septal mitral annular displacement (1.0 vs. 1.5 vs. 1.5 cm, P < 0.001). New York Heart Association (NYHA) class III/IV symptoms were the most frequent in the LFLG group (29 vs. 11 vs. 3%, P < 0.001). Survival at 3 years was significantly lower in LFLG compared with NFLG (P = 0.006) and moderate AS (P = 0.002), but not different between NFLG and moderate AS (P = 0.49). Higher NYHA classification (HR 1.77, 95% CI 1.22-2.57), RWT > 50% (HR 3.28, 95% CI 1.33-8.1), and septal displacement <1.1 cm (HR 3.93, 95% CI 1.96-7.82) but not low flow were independent predictors of survival in Cox proportional hazards analysis. CONCLUSION: Preserved ejection fraction, LFLG AS patients exhibit marked concentric remodelling and impaired longitudinal functional-features that predict their poor long-term survival. Normal-flow, low-gradient AS patients have outcomes similar to moderate AS.

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.

Aortic sclerosis is associated with mortality and major morbidity in patients undergoing coronary artery bypass surgery.

OBJECTIVE: In this study, we aim to investigate the association between aortic sclerosis and mortality and major morbidity in patients with established coronary artery disease undergoing coronary artery bypass grafting (CABG). DESIGN: Preoperative echocardiograms of consecutive patients undergoing isolated CABG between 2007 and 2009 (n=1150) were analysed, excluding patients without an echocardiogram in the 30 days prior to surgery (n=483). Using logistic regression, we evaluated the association between aortic sclerosis and inhospital mortality and major morbidity. Using Cox proportional hazards, the effect on long-term all-cause mortality was determined. SETTING: Massachusetts General Hospital, Boston. PATIENTS: Patients undergoing isolated CABG between 2007 and 2009. INTERVENTIONS: Analysis of echocardiograms. MAIN OUTCOME MEASURES: Inhospital mortality and major morbidity, and long-term all-cause mortality. RESULTS: 627 patients were suitable for enrolment; 207 (33%) had significant aortic sclerosis. These patients had higher rates of traditional cardiovascular risk factors. Significant aortic sclerosis was associated with an increased risk of inhospital mortality or major morbidity (OR 1.95; 95% CI 1.25 to 3.04). Following adjustment for baseline clinical and echocardiographic variables, the association remained significant (OR 1.90; 95% CI 1.15 to 3.11). The HR for adjusted all-cause mortality was 2.52 (mean follow-up 2.7 years). CONCLUSIONS: Aortic sclerosis is a common finding in patients undergoing CABG. In these patients, its presence is associated with a higher risk of inhospital mortality or major morbidity, and is associated with a higher risk of all-cause long-term mortality independent of other risk factors.

In vivo noninvasive characterization of brown adipose tissue blood flow by contrast ultrasound in mice.

BACKGROUND: Interventions to increase brown adipose tissue (BAT) volume and activation are being extensively investigated as therapies to decrease the body weight in obese subjects. Noninvasive methods to monitor these therapies in animal models and humans are rare. We investigated whether contrast ultrasound (CU) performed in mice could detect BAT and measure its activation by monitoring BAT blood flow. After validation, CU was used to study the role of uncoupling protein 1 and nitric oxide synthases in the acute regulation of BAT blood flow. METHODS AND RESULTS: Blood flow of interscapular BAT was assessed in mice (n=64) with CU by measuring the signal intensity of continuously infused contrast microbubbles. Blood flow of BAT estimated by CU was 0.5±0.1 (mean±SEM) dB/s at baseline and increased 15-fold during BAT stimulation by norepinephrine (1 µg·kg(-1)·min(-1)). Assessment of BAT blood flow using CU was correlated to that performed with fluorescent microspheres (R(2)=0.86, P<0.001). To evaluate whether intact BAT activation is required to increase BAT blood flow, CU was performed in uncoupling protein 1-deficient mice with impaired BAT activation. Norepinephrine infusion induced a smaller increase in BAT blood flow in uncoupling protein 1-deficient mice than in wild-type mice. Finally, we investigated whether nitric oxide synthases played a role in acute norepinephrine-induced changes of BAT blood flow. Genetic and pharmacologic inhibition of nitric oxide synthase 3 attenuated the norepinephrine-induced increase in BAT blood flow. CONCLUSIONS: These results indicate that CU can detect BAT in mice and estimate BAT blood flow in mice with functional differences in BAT.