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Background: There are significant sex and age differences in left ventricular (LV) remodeling that may lead to disparity in outcomes when used to inform the timing of aortic regurgitation (AR) intervention., Objectives: The aim of this study was to examine whether left atrial (LA) parameters might represent better criteria than LV parameters to inform the timing of AR intervention., Methods: Using data on patients with moderate to severe or severe AR with serial echocardiography (2010-2016), the longitudinal trends in left atrial volume index (LAVI) and left atrial reservoir strain (LAr) were evaluated by sex and age. The incremental utility of these parameters in predicting adverse events over LV parameters was also determined., Results: In 525 patients (25.7% women) with 1,687 echocardiograms over a median follow-up period of 2.0 years (Q1-Q3: 1.0-3.6 years), there was significant increase in LAVI (1.0 mL/m 2 per year [95% CI: 0.76-1.2 mL/m 2 per year]) and decrease in LAr (-1.3% per year [95% CI: -1.6% to -0.92%]), without a significant interaction by sex or age category (P for interaction ≥ 0.17). In addition, both LAVI and LAr were significant predictors of adverse events independent of LV parameters. The optimal discriminatory thresholds were 37 mL/m 2 for LAVI and 35% for LAr. These thresholds were similar across categories of sex and age. Within the relatively short-term follow-up, surgery was associated with survival benefit among patients with LAVI ≥37 mL/m 2 (HR: 0.33 [95% CI: 0.15-0.72]; P = 0.006) but was not statistically significant among patients with LAVI <37 mL/m 2 (HR: 0.46 [95% CI: 0.18-1.17]; P = 0.09). Similarly, surgery was associated with survival for the subgroup with LAr ≤35% but not among those with LAr >35%., Conclusions: Unlike LV remodeling, LA remodeling demonstrates a similar rate of progression between categories of sex and age among patients with AR. In addition, LA parameters provide incremental prognostic value over LV parameters., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The current guidelines for the management and treatment of acute coronary syndromes do not fully consider the role of age in guiding medical or invasive management. We investigated the characteristics, management strategies, and clinical outcomes of patients aged 80 years and older presenting with non-ST elevation myocardial infarction (NSTEMI). A cohort study using the nationwide inpatient sample database of patients aged 80 years and older presenting with NSTEMI in the United States between 2012 to 2018 was performed. About 24.2% (151,472/625,916) of NSTEMI patients were 80 years and older. Older patients (≥80 years) had higher in-hospital mortality and cardiovascular complications compared to younger patients (odds ratio (OR) 1.79, 95% confidence intervals (CI) 1.71-1.88, P < 0.001). Among older patients, conservative medical management was associated with higher inpatient mortality compared to percutaneous coronary intervention (PCI) (OR 2.3, 95% CI 2.18-2.41, P < 0.001) or coronary artery bypass graft (CABG) (OR 1.9, 95% CI 1.76-2.09, P < 0.001). The highest mortality rate was observed in older patients who underwent both PCI and CABG, followed by those treated conservatively and those undergoing coronary angiography without revascularization. This study provides valuable insights into the clinical characteristics and outcomes of elderly patients presenting with NSTEMI in the United States. The results emphasize the importance of a tailored approach to the management of ACS in elderly patients and the need for improved revascularization strategies to reduce in-hospital mortality and adverse cardiovascular outcomes. Therefore, the clinician should tailor the management of older patients presenting with NSTEMI., Competing Interests: Declaration of Competing Interest Dr. Kapadia receives fees of $5,000 or more per year (or, in rare cases, equity or stock options) as a paid consultant, speaker, or as member of an advisory committee for Anteris Technologies. Dr. Kapadia receives or has the right to receive royalty payments for inventions or discoveries commercialized through Bavaria Medizin Technologie GmbH. Dr. Kapadia may receive future financial benefits from the Cleveland Clinic for inventions or discoveries commercialized through Mitria Medical, LLC, Bavaria Medizin Technologie GmbH. All other authors have no disclosures., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Data regarding mitral regurgitation (MR) in extremely elderly patients are limited. The aim of the present study was to assess symptomatic status, frailty, etiology and outcomes for nonagenarians with severe MR., Methods: Single-center cohort study of patients ≥90 years of age with at least 3+ MR on echocardiography between September 2010 and August 2018. Out of a total of 11,998 patients with at least 3+ MR, 267 patients were included in the present study., Results: The average age was 93.5 ± 2.6 years, and 57% were female. At baseline, 88% were symptomatic, with mean Charlson co-morbidity index of 6 ± 2 points, and mean frailty score of 2.9 ± 1.4 points. Primary MR was present in 50%, secondary in 47%, and prosthetic valve dysfunction in 3%. Among patients with primary MR, the most common etiology was mitral annular calcification (58%). In comparison, the most common etiology of secondary MR was atrial functional MR (52%). Of all, 95% were treated conservatively, and 5% underwent interventional management. Among 253 patients who had follow-up data with a median follow-up of 14 months (25th-75th interquartile range: 3-31 months), 191 patients (75%) died. Mortality trended higher in the conservative group versus the interventional group (60% vs. 22%, log-rank P = 0.063)., Conclusions: Most nonagenarians with significant MR were symptomatic at presentation, had elevated Charlson co-morbidity index and frailty scores. Etiologies of MR were almost equally distributed between primary and secondary causes. The vast majority of nonagenarians with significant MR were conservatively managed., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The objective of the study was to construct a multi-parametric mitral annular calcification (MAC) score using computed tomography (CT) features for prediction of outcomes in patients undergoing mitral valve surgery. We constructed a multi-parametric MAC score, which ranges between 2 and 12, and consists of Agatston calcium score (1 point: <1000 Agatston units (AU); 2 points: 1000-<3000 AU; 3 points: 3000-5000 AU; 4 points: >5000 AU), quantitative MAC circumferential angle (1 point: <90°; 2 points: 90-<180°; 3 points: 180-<270°; 4 points: 270-360°), involvement of trigones (1 point: 1 trigone; 2 points: both trigones), and 1 point each for myocardial infiltration and left ventricular outflow tract extension/involvement of aorto-mitral curtain. The association between MAC score and clinical outcomes was evaluated. The study cohort consisted of 334 patients undergoing mitral valve surgery (128 mitral valve repairs, 206 mitral valve replacements) between January 2011 and September 2019, who had both non-contrast gated CT scan and evidence of MAC. The mean age was 72 ± 11 years, with 58% of subjects being female. MAC score was a statistically significant predictor of total operation time (P<0.001), cross-clamp time (P = 0.001) and in-hospital complications (P = 0.003). Additionally, MAC score was a significant predictor of time to all-cause death (P = 0.046). A novel multi-parametric score based on CT features allowed systematic assessment of MAC, and predicted clinical outcomes in patients with mitral valve dysfunction undergoing mitral valve surgery., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Significant tricuspid regurgitation (TR) is associated with poor outcome and high operative mortality resulting from late presentation. Yet, the optimal timing for intervention is unknown., Objectives: The purpose of this study was to evaluate the prognostic value of echocardiographic parameters to inform early intervention in asymptomatic TR., Methods: Using the Cleveland Clinic echocardiography database 2004 to 2018, the authors identified a consecutive cohort of asymptomatic patients with moderate to severe (3+) or severe (4+) TR. Quantitative TR and right heart parameters were retrospectively determined, and their prognostic utility for all-cause mortality was assessed., Results: In 325 asymptomatic patients (mean age: 67.9 years; 79.4% female) with at least 3+ TR, there were 132 deaths (40.6%), with a median survival time of 9.9 years (95% CI: 7.9-12.7 years). By contrast, the median survival time in an age- and sex-matched cohort of symptomatic TR patients was 4.4 years (95% CI: 2.8-5.9 years). Among all the echocardiographic parameters evaluated, right ventricle free wall strain (RVFWS) and tricuspid regurgitant volume (RVol) were the strongest predictors of mortality in asymptomatic TR. The optimal discriminatory thresholds for these parameters were RVFWS <-19% and RVol >45 mL. The 5-year survival rates by number of risk factors (RF) were 93% (95% CI: 86%-96%), 65% (95% CI: 55%-74%), and 38% (95% CI: 26%-49%) for no RF, 1 RF, and both RFs, respectively. Compared with symptomatic TR, mortality was lower for asymptomatic TR with no RF (HR: 0.10; 95% CI: 0.04-0.29) or 1 RF (HR: 0.29; 95% CI: 0.14-0.58), but similar for asymptomatic TR with both RFs (HR: 1.11; 95% CI: 0.56-2.19)., Conclusions: RVFWS and RVol are key prognostic markers that can be serially monitored to inform optimal timing of intervention for severe asymptomatic TR., Competing Interests: Funding Support and Author Disclosures Dr Gillinov has served as a consultant to AtriCure, Medtronic, Edwards Lifesciences, CryoLife, Abbott, and ClearFlow; and has rights to equity in ClearFlow. Dr Desai has been supported by the Haslam Family endowed chair in cardiovascular medicine at the Cleveland Clinic. The current research was supported by a philanthropic gift from the Haslam family, Bailey family, and Khouri family. Dr Desai has research and consulting agreements with Bristol Myers Squibb, Medtronic, and Caristo Diagnostics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The authors report etiologies and outcomes and devise a risk model in a large contemporary cohort of patients with isolated tricuspid regurgitation (TR)., Background: Isolated TR is a challenging clinical entity with heterogeneous etiology and often poor outcomes, with a paucity of recent research regarding the epidemiology of isolated TR., Methods: Consecutive patients with isolated TR graded at least moderate to severe on echocardiography from January 2004 to December 2018 (n = 9,045, mean age 70.4 ± 15.4 years, 60.3% women) were studied. TR etiologies were individually adjudicated as secondary or primary, with subcategories. All-cause death during follow-up was the primary endpoint, with associations between etiology and outcomes analyzed and a risk model created., Results: Primary and secondary TR etiologies were present in 470 (5.2%) and 8,575 (94.8%) patients, respectively. The main secondary etiologies were left heart disease in 4,664 (54.4%), atrial functional in 2,086 (24.3%), and pulmonary disease in 1,454 (17.0%), and the main primary etiologies were endocarditis in 222 (47.2%), degenerative or prolapse in 86 (18.3%), and prosthetic valve failure in 79 (16.8%). There were 3,987 deaths (44.0%) over a mean follow-up period of 2.6 ± 3.3 years. In unadjusted analyses, patients with secondary TR had worse survival than those with primary TR (HR: 1.56; 95% CI: 1.32-1.85), but this result was not statistically significant in multivariable analysis. The authors devised and internally validated a risk score for predicting 1-year mortality in these patients., Conclusions: Secondary TR constituted 95% of isolated significant TR and conferred worse survival than primary TR in unadjusted but not adjusted analyses. The present novel risk score stratifies the risk for 1-year death and may influence decision making for management in these high-risk patients., Competing Interests: Funding Support and Author Disclosures Dr Wang is supported by the National Heart Foundation of New Zealand Overseas Clinical and Research Fellowship (grant 1775). Dr Desai is supported by the Haslam Family endowed chair in cardiovascular medicine at the Cleveland Clinic, a generous philanthropic gift from the Haslam family, Bailey family, and Khouri family. Dr Desai has research and consulting agreements with Myokardia, Medtronic, and Silence Therapeutics. Dr Gillinov is a consultant to AtriCure, Medtronic, Edwards Lifesciences, CryoLife, Abbott, Johnson & Johnson, and ClearFlow; and has rights to equity in ClearFlow. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Transcatheter aortic valve replacement-associated infective endocarditis (TAVR-IE) is a relatively rare complication of TAVR. Little is known about the characteristics of early, intermediate, and late-onset TAVR-IE., Methods: We studied the risk factors, microbiological patterns, and diagnostic and treatment strategies in patients with early (<60 days), intermediate (60-365 days), and late-onset (>1 year) TAVR-IE., Results: Ten out of 494 definite cases of prosthetic valve IE between 2007 and 2019 were confirmed to have TAVR-IE from the IE registry at our center. The mean age was 78.1 ± 13.7 years, with 50% being female. The mean Society of Thoracic Surgeons risk score was 7.8 ± 5.7. Most (60%) TAVR-IE cases had an intermediate onset, with Staphylococcus aureus being the most common organism (66.6%). 18-fluorodeoxyglucose positron emission tomography aided in diagnosis of TAVR-IE in 20% of cases. Mortality due to IE was observed in 40% of cases. Most of the patients underwent conservative management, and 37.5% survived over a mean follow-up of 709 ± 453 days. Two patients underwent surgery, of whom one died on day 30 postoperatively from sepsis. Mortality due to IE occurred in 25% of cases in the early and intermediate-onset groups, while there was 100% mortality in the late-onset group., Conclusions: In a single-center cohort, most TAVR-IE cases had an intermediate onset, with Staphylococcus aureus being the most common organism. Understanding timing of TAVR-IE may have important prognostic implications., Competing Interests: The authors report no conflict of interest. This work represents original research of all authors and is not published elsewhere. The abstract of this work was presented at the 2020 Scientific Sessions of American Heart Associations., (© 2022 The Author(s).)

Objectives: The aims of this study were to characterize the interplay between mixed aortic valve disease (MAVD) phenotypes (defined by concomitant severities of aortic stenosis and aortic regurgitation) and left ventricular global longitudinal strain (LV-GLS), and to assess the prognostic utility of LV-GLS in MAVD., Background: Little is known about the way LV-GLS separates MAVD phenotypes and if it is associated with their outcomes., Methods: This observational cohort study evaluated 783 consecutive adult patients with left ventricular ejection fraction ≥50% and MAVD, which was defined as coexisting with at least moderate aortic stenosis and at least moderate aortic regurgitation. We measured the conventional echocardiographic variables and average LV-GLS from apical long, 2- and 4-chamber views. The primary endpoint was all-cause mortality., Results: Mean age of patients was 69 ± 15 years, and 58% were male. Mean LV-GLS was -14.7 ± 2.9%. In total, 458 patients (59%) underwent aortic valve replacement at a median period of 50 days (25th to 75th percentile range: 6 to 560 days). During a median follow-up period of 5.6 years (25th to 75th percentile range: 1.8 to 9.4 years), 391 patients (50%) died. When stratified patients into tertiles according to LV-GLS values, patients with worse LV-GLS had worse outcomes (p < 0.001). LV-GLS was independently associated with mortality (hazard ratio: 1.09; 95% confidential intervals: 1.04 to 1.14; p < 0.001), with the relationship between LV-GLS and mortality being linear., Conclusions: LV-GLS is associated with all-cause mortality. LV-GLS may be useful for risk stratification in patients with MAVD., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Mitral annular disjunction (MAD) is an increasingly recognized entity associated with mitral valve prolapse (MVP), ventricular arrhythmias and death. Few studies have investigated the utility of myocardial deformation analysis in MAD. We compared chamber quantification including strain by transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (CMR) between MVP patients with and without MAD., Methods: Forty-two patients with MVP (21 with MAD, 21 without MAD) and 21 controls were studied. Global, basal and basal inferolateral (BIL) segmental strains were measured and compared using velocity-vector imaging TTE and feature-tracking CMR., Results: Mean age was 54 ± 17 years, 19 (46%) were female, and 19 (46%) underwent surgical mitral valve repair with no deaths during follow-up in the 2 groups with MVP. Patients with MAD and MVP had lower basal longitudinal strain by TTE than those with MVP without MAD. Those with MAD and MVP had lower magnitude in BIL and basal segments by circumferential and radial strain by CMR compared to those with MVP without MAD and controls. Amongst global strain parameters, CMR-derived global circumferential strain was independently associated with MAD diagnosis odds ratio 1.49 (per 1%), 95% confidence interval 1.09-2.05, P = 0.014, with optimal threshold of -18.0% having 76% sensitivity and specificity for MAD., Conclusion: Abnormal circumferential and radial strain patterns in the basal segments by CMR may be useful for identifying regional LV dysfunction associated with MAD., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: A substantial proportion of infective endocarditis (IE) cases are complicated by local invasion. The purpose of this study was to identify patient and disease characteristics associated with local invasion in surgically treated IE patients., Methods: This was a nested case-control study. All episodes of IE for patients admitted to Cleveland Clinic from 1 January 2013 to 30 June 2016 were identified from the Cleveland Clinic IE Registry. Patients ≥18 years of age who underwent surgery for IE were included. Among these, cases were those with local invasion, controls were those without. Local invasion, defined as periannular extension, paravalvular abscess, intracardiac fistula or pseudoaneurysm, was ascertained from the surgical operative note. Associations of selected factors with local invasion were examined in a multivariable logistic regression model., Results: Among 511 patients who met inclusion criteria, 215 had local invasion. Mean age was 56 years; 369 were male. Overall 345 (68%) had aortic valve, 228 (45%) mitral valve, and 66 (13%) tricuspid or pulmonic valve involvement. Aortic valve involvement (OR 6.23, 95% CI 3.55-11.44), bioprosthetic valve (OR 3.88, 95% CI 2.36-6.44), significant paravalvular leak (OR 3.80, 95% CI 1.60-9.89), new atrioventricular nodal block (OR 3.77, 95% CI 1.87-7.90), infection with streptococci other than viridans group streptococci (OR 7.54, 95% CI 2.42-24.87) and presence of central nervous system emboli (OR 1.85, 95% CI 1.13-3.04) were associated with local invasion., Discussion: Intracardiac and microorganism factors, but not comorbid conditions, are associated with local invasion in IE., (Copyright © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objectives: This study was designed to compare the clinical and echocardiographic characteristics, management, and outcomes of severe atrial functional mitral regurgitation (AFMR) to primary mitral regurgitation (PMR)., Background: AFMR remains poorly defined clinically., Methods: Consecutive patients who underwent transesophageal echocardiography at our institution between 2011 and 2018 for severe mitral regurgitation with preserved left ventricular function were screened. We excluded patients with endocarditis, any form of cardiomyopathy, or prior mitral intervention. The absence of leaflet pathology defined AFMR. Outcomes included death and heart failure hospitalizations., Results: A total of 283 patients were included (AFMR = 14%, PMR = 86%). Compared to PMR, patients with AFMR had more comorbidities, including hypertension (94.9% vs. 76.2%; p = 0.015), diabetes mellitus (46.2% vs. 18.4%; p < 0.001), long-standing atrial fibrillation (28.2% vs. 13.1%; p = 0.015), prior nonmitral cardiac surgery (25.6% vs. 9.8%; p = 0.004), and pacemaker placement (33.3% vs. 13.5%; p = 0.002). They also had higher average E/e' (median [interquartile range]:16.04 [13.1 to 22.46] vs. 14.1 [10.89 to 19]; p = 0.036) and worse longitudinal left atrial strain peak positive value (16.86 ± 12.15% vs. 23.67 ± 14.09%; p = 0.002) compared to PMR. During follow-up (median: 22 months), patients with AFMR had worse survival (log-rank p = 0.009) and more heart failure hospitalizations (log-rank p = 0.002). They were also less likely to undergo mitral valve intervention (59.0% vs. 83.6%; p = 0.001), although surgery was associated with improved survival (log-rank p = 0.021). On multivariable regression analysis, AFMR was independently associated with mortality [adjusted odds ratio: 2.61, 95% confidence interval: 1.17 to 5.83; p = 0.02]., Conclusions: AFMR constitutes an under-recognized high-risk group, with significant comorbidities, limited therapeutic options, and poor outcomes., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to evaluate the role of cardiac magnetic resonance (CMR) for the quantification of ischemic mitral regurgitation (IMR) and myocardial infarct size (MIS) in patients with ischemic cardiomyopathy (ICM). This study also sought to explore the interaction between IMR severity and MIS and its association with outcomes in patients with ICM., Background: IMR occurs secondary to a disease of the left ventricle and is associated with poor outcomes. The role of CMR for the evaluation and risk stratification of patients with ICM and IMR remains uncertain., Methods: Consecutive patients with ICM who underwent baseline CMR were included. MIS was quantified on late gadolinium enhancement imaging as the proportion of left ventricular mass. IMR was quantified with CMR by calculating the mitral regurgitant fraction (MRFraction). Cox proportional hazards models were built to assess the association of IMR and MIS quantification with the combined endpoint of all-cause death or heart transplant., Results: We evaluated 578 patients (mean age: 62 ± 11 years, 76% males). The mean left ventricular ejection fraction was 25 ± 11%, with an MIS of 24 ± 16% and MRFraction of 18 ± 17%. Over a median follow-up time of 4.9 years, 198 (34%) patients experienced death or cardiac transplant. On multivariable analysis, after comprehensive medical risk score, subsequent revascularization, implantable cardioverter-defibrillator insertion, and surgical mitral valve intervention were controlled for, the interaction of IMR severity and MIS emerged as a powerful predictor of adverse outcomes (p = 0.008). For patients with significant IMR (MRFraction: ≥35%), the hazard ratio comparing moderate MIS (15% to 29%) versus small MIS (<15%) was 1.51 (0.57 to 3.98), and the hazard ratio comparing large MIS (≥30%) versus small MIS was 5.41 (2.34 to 12.7)., Conclusions: Risk associated with IMR is more comprehensively described as an interaction between IMR severity and MIS. Further studies in patients IMR using comprehensive CMR evaluation are needed to verify whether this approach can improve patient selection and procedural outcomes to address IMR., (Copyright © 2020. Published by Elsevier Inc.)

Background: Prosthetic valve endocarditis (PVE) is a serious condition with high morbidity and mortality. This study investigated the association of surgical treatment with survival among patients with PVE., Methods: A retrospective cohort study was done of patients with PVE hospitalized over 8 years in a large referral center. Association of surgery with survival was evaluated with multivariable Cox proportional hazards regression, adjusting for propensity to be accepted for surgery, and analyzing surgery as a time-dependent covariate. Survival was also compared separately in a 1:1 propensity score-matched cohort of patients accepted for surgery and control patients consigned to nonsurgical treatment., Results: Of 523 patients (mean [SD] age, 61 [14] years; 370 [71%] men; 393 [75%] initially accepted for surgery), 404 ultimately underwent surgery and 119 received nonsurgical treatment alone. Surgical treatment was associated with significantly lower hazard of death in the entire cohort (hazard ratio [HR] = 0.32; 95% confidence interval [CI]: 0.22-0.48; P < .001) and in the 1:1 matched cohort (HR = 0.33; 95% CI: 0.19-0.57; P < .001). Initial acceptance for surgery was associated with significantly lower odds of in-hospital death (odds ratio [OR] = 0.26; 95% CI: 0.11-0.59; P < .001), death or readmission within 90 days (OR = 0.17; 95% CI: 0.07-0.43; P < .001), and death within 1 year (OR = 0.16; 95% CI: 0.08-0.34; P < .001)., Conclusions: Surgical treatment is associated with a large survival benefit in PVE. A decision to pursue nonsurgical treatment in PVE should entail close follow-up for any development of an indication for surgery., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to determine whether baseline left ventricular global longitudinal strain (LV-GLS) and changes in left ventricular ejection fraction (LVEF) in a subgroup of subjects at post-operative follow-up added prognostic value in patients undergoing aortic valve (AV) surgery., Background: In patients with chronic severe aortic regurgitation (AR) and preserved LVEF, sensitive markers are needed to decide timing of AV surgery., Methods: This was an observational study in 865 patients (asymptomatic/mildly symptomatic, 52 ± 15 years of age, 79% men) with ≥3+ chronic AR and preserved LVEF of ≥50% who underwent AV surgery between 2003 and 2015. All patients had baseline echocardiography (and LV-GLS imaging), whereas 285 patients underwent post-operative echocardiography (including LV-GLS). Primary outcome was mortality., Results: Only 478 patients (56%) patients had preoperative LV-GLS values better than -19%, despite a mean LVEF of 57 ± 4%. At a median 38 days, 632 patients underwent AV replacement, whereas 233 patients had AV repair. At a median follow-up of 6.95 (interquartile range [IQR]: 5.2 to 9.1) years, 105 patients (12%) died (2% in-hospital deaths). A higher proportion of patients with baseline LV-GLS grades worse than -19% died versus those whose LV-GLS score was better (15% vs. 10%; p < 0.01), and worse LV-GLS value was independently associated with higher longer-term mortality (hazard ratio: 1.62; 95% confidence interval [CI]: 1.40 to 1.86]; p < 0.001). In the 285 patients who underwent echo at 3 to 12 months post-operatively, LVEF normalized in 91% patients; however, only 88 patients (31%) had LV-GLS values better than -19%. Patients whose follow-up LV-GLS value was better than -19% had significantly better longer-term survival than those whose LV-GLS was not (5% vs. 15%, respectively; p < 0.01). An absolute worsening of 5% of LV-GLS from baseline was associated with increased mortality., Conclusions: In patients with ≥3+ chronic AR and preserved LVEF undergoing AV surgery, a baseline LV-GLS value worse than -19% was associated with reduced survival. In a subgroup of patients who returned for 3- and 12-month follow-up examinations, persistently impaired LV-GLS was associated with increased mortality., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The authors review the optimal sequence of multimodality imaging studies in patients with chronic asymptomatic aortic regurgitation (AR). The initial questions in evaluating such patients are: 1) is AR severe; and 2) does it significantly impact the left ventricle? Although transthoracic echocardiography is usually able to answer these questions, a cardiovascular magnetic resonance imaging study might be necessary if the data from echocardiography are conflicting or inadequate. If AR is severe and the left ventricle is severely dilated, surgery is indicated. If AR is severe but the left ventricle is not significantly impacted, echocardiographic exercise testing might unmask symptoms. If aortopathy is suspected, cardiovascular magnetic resonance (in younger patients) or computed tomography (in older patients) is necessary. In cases where AR severity or mechanism are unclear and no additional tests are possible, or if there is a potential for aortic valve repair, transesophageal echocardiography is appropriate. Finally, it is good practice to define a follow-up plan with the patient and referring physician, with an explanation as to what can be expected in the future., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Coronary artery inflammation inhibits adipogenesis in adjacent perivascular fat. A novel imaging biomarker-the perivascular fat attenuation index (FAI)-captures coronary inflammation by mapping spatial changes of perivascular fat attenuation on coronary computed tomography angiography (CTA). However, the ability of the perivascular FAI to predict clinical outcomes is unknown., Methods: In the Cardiovascular RISk Prediction using Computed Tomography (CRISP-CT) study, we did a post-hoc analysis of outcome data gathered prospectively from two independent cohorts of consecutive patients undergoing coronary CTA in Erlangen, Germany (derivation cohort) and Cleveland, OH, USA (validation cohort). Perivascular fat attenuation mapping was done around the three major coronary arteries-the proximal right coronary artery, the left anterior descending artery, and the left circumflex artery. We assessed the prognostic value of perivascular fat attenuation mapping for all-cause and cardiac mortality in Cox regression models, adjusted for age, sex, cardiovascular risk factors, tube voltage, modified Duke coronary artery disease index, and number of coronary CTA-derived high-risk plaque features., Findings: Between 2005 and 2009, 1872 participants in the derivation cohort underwent coronary CTA (median age 62 years [range 17-89]). Between 2008 and 2016, 2040 patients in the validation cohort had coronary CTA (median age 53 years [range 19-87]). Median follow-up was 72 months (range 51-109) in the derivation cohort and 54 months (range 4-105) in the validation cohort. In both cohorts, high perivascular FAI values around the proximal right coronary artery and left anterior descending artery (but not around the left circumflex artery) were predictive of all-cause and cardiac mortality and correlated strongly with each other. Therefore, the perivascular FAI measured around the right coronary artery was used as a representative biomarker of global coronary inflammation (for prediction of cardiac mortality, hazard ratio [HR] 2·15, 95% CI 1·33-3·48; p=0·0017 in the derivation cohort, and 2·06, 1·50-2·83; p<0·0001 in the validation cohort). The optimum cutoff for the perivascular FAI, above which there is a steep increase in cardiac mortality, was ascertained as -70·1 Hounsfield units (HU) or higher in the derivation cohort (HR 9·04, 95% CI 3·35-24·40; p<0·0001 for cardiac mortality; 2·55, 1·65-3·92; p<0·0001 for all-cause mortality). This cutoff was confirmed in the validation cohort (HR 5·62, 95% CI 2·90-10·88; p<0·0001 for cardiac mortality; 3·69, 2·26-6·02; p<0·0001 for all-cause mortality). Perivascular FAI improved risk discrimination in both cohorts, leading to significant reclassification for all-cause and cardiac mortality., Interpretation: The perivascular FAI enhances cardiac risk prediction and restratification over and above current state-of-the-art assessment in coronary CTA by providing a quantitative measure of coronary inflammation. High perivascular FAI values (cutoff ≥-70·1 HU) are an indicator of increased cardiac mortality and, therefore, could guide early targeted primary prevention and intensive secondary prevention in patients., Funding: British Heart Foundation, and the National Institute of Health Research Oxford Biomedical Research Centre., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objectives: The aim of this study was to study differences in progression of aortic stenosis (AS) in patients with mediastinal radiotherapy (XRT)-associated moderate AS versus a matched cohort during the same time frame, and to ascertain need for aortic valve replacement (AVR) and longer-term survival., Background: Rate of progression of XRT-associated moderate AS and its impact on outcomes is not well-described., Methods: We included 81 patients (age 61 ± 13 years; 57% female) with at least XRT-associated moderate AS (aortic valve area [AVA] 1.05 ± 0.3 cm 2 ; mean gradient 24 ± 10 mm Hg) who had ≥2 transthoracic echocardiograms (TTEs) 1 year apart and matched them in a 1:2 fashion on the basis of age, sex, and AVA with those without prior XRT. Serial aortic valve gradients and AVA were recorded. AVR and longer-term all-cause mortality during follow-up were recorded., Results: A total of 100% of patients had 1, a total of 71% had 2, and 39% had 3 follow-up TTEs. Before AVR, mean AVG and AVA were not significantly different between XRT and comparison groups. At 3.6 ± 2.0 years from baseline TTE, 146 (60%) underwent AVR (16% transcatheter), with significantly more patients in the XRT group undergoing AVR (80% vs. 50%; p < 0.01), at a much shorter time (2.9 ± 1.6 years vs. 4.1 ± 2.4 years; p < 0.01). At 6.6 ± 4.0 years from the initial TTE, 49 (20%) patients died, with a significantly higher mortality in the XRT group (40% vs. 11%; p < 0.01), with prior XRT associated with increased longer-term mortality, whereas AVR was associated with improved longer-term survival., Conclusions: In patients with moderate AS, those with prior XRT have a similar rate of progression of AS versus a comparison group. A higher proportion of patients in the XRT group were referred for AVR at a shorter time from baseline TTE. Despite that, the XRT patients had significantly higher longer-term mortality, and prior exposure to XRT was associated with significantly increased longer-term mortality., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Radiation-associated cardiac disease (RACD) results in complex clinical presentations, unique management issues, and increased morbidity and mortality. Patients typically present years or even decades after radiation exposure, with delayed-onset cardiac damage sustained from high cumulative doses. Multimodality imaging is crucial to determine the manifestations and severity of disease because symptoms are often nonspecific. Comprehensive screening using a coordinated approach may enable early detection. However, timing of intervention should be carefully considered in these patients because surgery is often complex and high-risk second surgeries should be minimized in the long-term. This review aims to provide treating physicians with a comprehensive and clinically focused overview of RACD, including clinical/imaging manifestations, multi-modality screening recommendations, and management options., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to examine the prognostic utility of left ventricular (LV) global longitudinal strain (GLS) in asymptomatic patients with ≥III+ aortic regurgitation (AR), an indexed LV end-systolic dimension of <2.5 cm/m 2 , and preserved left ventricular ejection fraction (LVEF)., Background: Management of asymptomatic patients with severe chronic AR and preserved LVEF is challenging and is typically based on LV dimensions., Methods: We studied 1,063 such patients (age 53 ± 16 years; 77% men) seen between 2003 and 2010 (excluding those with symptoms, obstructive coronary artery disease, acute AR/dissection, aortic/mitral stenosis, more than moderate mitral regurgitation, and previous cardiac surgery). Society of Thoracic Surgeons (STS) score was calculated. The primary endpoint was mortality. Average resting LV-GLS was measured offline on 2-, 3-, and 4-chamber views using Velocity Vector Imaging (Siemens, Malvern, Pennsylvania)., Results: Mean STS score, LVEF, LV-GLS, and right ventricular systolic pressure were 4.4 ± 5.0%, 57.0 ± 4.0%, -19.5 ± 0.2%, and 31.0 ± 9.0 mm Hg, respectively. In total, 671 patients (63%) underwent aortic valve surgery at a median of 42 days after the initial evaluation. At 6.8 ± 3.0 years, 146 patients (14%) had died. On multivariable Cox survival analysis, LV-GLS (hazard ratio [HR]: 1.11), STS score (HR: 1.51), indexed LV end-systolic dimension (HR: 0.50), right ventricular systolic pressure (HR: 1.33), and aortic valve surgery (HR: 0.35) were associated with longer term mortality (all p < 0.001). Sequential addition of LV-GLS and aortic valve surgery improved the C-statistic for longer term mortality for the clinical model (STS score + right ventricular systolic pressure + indexed LV end-systolic dimension) from 0.61 (95% confidence interval [CI]: 0.51 to 0.72) to 0.67 (95% CI: 0.54 to 0.87) and to 0.77 (95% CI: 0.63 to 0.90), respectively (p < 0.001 for both). A significantly higher proportion (log-rank p = 0.01) of patients with LV-GLS worse than median (-19.5%) died versus those with an LV-GLS better than median (86 of 513 [17%] vs. 60 of 550 [11%]). The risk of death at 5 years significantly increased with an LV-GLS of worse than -19%., Conclusions: In asymptomatic patients with ≥III+ chronic AR and preserved LVEF, worsening LV-GLS was associated with longer term mortality, providing incremental prognostic value and improved reclassification., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Epithelial-Mesenchymal Transition (EMT) is a dynamic process through which epithelial cells transdifferentiate from an epithelial phenotype into a mesenchymal phenotype. Previous studies have demonstrated that both mechanical signaling and soluble growth factor signaling facilitate this process. One possible point of integration for mechanical and growth factor signaling is the extracellular matrix. Here we investigate the role of the extracellular matrix (ECM) protein fibronectin (FN) in this process. We demonstrate that inhibition of FN fibrillogenesis blocks activation of the Transforming Growth Factor-Beta (TGF-β) signaling pathway via Smad2 signaling, decreases cell migration and ultimately leads to inhibition of EMT. Results show that soluble FN, FN fibrils, or increased contractile forces are insufficient to independently induce EMT. We further demonstrate that inhibition of latent TGF-β1 binding to FN fibrils via either a monoclonal blocking antibody against the growth factor binding domain of FN or through use of a FN deletion mutant that lacks the growth factor binding domains of FN blocks EMT progression, indicating a novel role for FN in EMT in which the assembly of FN fibrils serves to localize TGF-β1 signaling to drive EMT., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Cardiac allograft vasculopathy (CAV), a major cause of graft failure and mortality at >3 years after orthotopic heart transplantation (OHT), is commonly evaluated using dobutamine stress echocardiography (DSE). We sought to study: (a) the incidence of positive results and diagnostic accuracy of DSE; and (b) the predictors of adverse outcomes in OHT patients., Methods: We studied 497 consecutive patients (63 ± 10 years, 78% men) with OHT who had undergone DSE as part of routine surveillance at our center between 1998 and 2013. Every DSE and coronary angiogram performed during follow-up was reviewed. CAV was regraded according to the 2010 recommendations of the International Society for Heart and Lung Transplantation. Composite events (death, coronary revascularization, myocardial infarction and retransplantation) were recorded., Results: There were 1,243 DSE studies performed during a median of 8.7 (6.2 to 11.9) years after transplantation. Only 22 studies (1.8%) were positive, 978 (78.7%) were negative and 243 (19.5%) were non-diagnostic (sub-maximal heart rate response) for ischemia. Among 497 patients, only 20 (4%) had at least one positive DSE study. There were 310 diagnostic DSEs with coronary angiograms performed within 1 year of one another other. In this subgroup, the sensitivity, specificity, positive predictive value and negative predictive value of DSE were 7%, 98%, 82% and 41%, respectively, to detect any CAV, and 28%, 98%, 71% and 89% to detect CAV Grades 2 or 3, respectively. There were no deaths during DSE. At 5.6 ± 3.6 years after DSE, there were 201 (40%) events. Degree of CAV (and not DSE-based ischemia, p = 0.3) independently predicted outcomes (p < 0.001)., Conclusions: The incidence of a positive result is very low in OHT patients undergoing surveillance DSE. DSE is insufficiently sensitive for detection of early CAV. Degree of CAV and not DSE-based ischemia independently predicted outcomes., (Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study hypothesized that regurgitation severity, as determined by using the regurgitant volume index, would better delineate differential cardiac dysfunction in asymptomatic patients with moderate to severe aortic regurgitation (AR) and mitral regurgitation (MR)., Background: Frequent surveillance echocardiography is considered appropriate in asymptomatic patients with moderate to severe AR and MR. However, the evidence to support this practice and to define the appropriate frequency is limited., Methods: This was an observational cohort study of consecutive patients with moderate to severe asymptomatic AR or MR who underwent exercise echocardiography. Our cohort included 130 patients with moderate to severe asymptomatic MR and 130 patients with moderate to severe asymptomatic AR who were matched according to age and regurgitant volume index. All patients underwent yearly echocardiographic follow-up studies. Regurgitation severity was determined according to regurgitant volume index, with a level ≥30 ml/m(2) considered a marker of severe regurgitation., Results: During follow-up, regardless of etiology, patients with severe regurgitation demonstrated increasing left ventricular volume indexes (4.2 ± 1.5 ml/m(2) per year; p = 0.01) and decreasing left ventricular ejection fractions (1.3 ± 0.4% per year; p = 0.002). In patients with moderate regurgitation, left ventricular volumes and ejection fractions did not significantly change. In addition, patients with severe regurgitation experienced a similar drop in contractility (end-systolic pressure/end-systolic volume ratio and single-beat pre-load recruitable stroke work) during follow-up independent of regurgitation etiology. Contractility parameters did not change in patients with moderate regurgitation., Conclusions: These asymptomatic patients with moderate AR or MR had stable cardiac function during 3 years of follow-up; thus, frequent echocardiography without a change in clinical status may not be necessary. In the setting of severe regurgitation, further cardiac deterioration occurred at a similar rate and manner irrespective of whether the dysfunction was related to AR or MR., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: We investigated the effects of lung transplantation on right ventricular (RV) function as well as the prognostic value of pre- and post-transplantation RV function., Background: Although lung transplantation success has improved over recent decades, outcomes remain a challenge. Identifying predictors of mortality in lung transplant recipients may lead to improved long-term outcomes after lung transplantation., Methods: Eighty-nine (age 60 ± 6 years, 58 men) consecutive patients who underwent single or double lung transplantation and had pre- and post-transplantation echocardiograms between July 2001 and August 2012 were evaluated. Echocardiographic measurements were performed before and after lung transplantation. Left ventricular (LV) and RV longitudinal strains were analyzed using velocity vector imaging. Cox proportional prognostic hazard models predicting all-cause death were built., Results: There were 46 all-cause (52%) and 17 cardiac (19%) deaths during 43 ± 33 months of follow-up. After lung transplantation, echocardiography showed improved systolic pulmonary artery pressure (SPAP) (50 ± 19 mm Hg to 40 ± 13 mm Hg) and RV strain (-17 ± 5% to -18 ± 4%). No pre-transplantation RV parameter predicted all-cause mortality. After adjustment for age, sex, surgery type, and etiology of lung disease in a Cox proportional hazards model, both post-transplantation RV strain (hazard ratio: 1.13, 95% confidence interval: 1.04 to 1.23, p = 0.005), and post-transplantation SPAP (hazard ratio: 1.03, 95% confidence interval: 1.01 to 1.05, p = 0.011) were independent predictors of all-cause mortality. When post-transplantation RV strain and post-transplantation SPAP were added the clinical predictive model based on age, sex, surgery type, and etiology, the C-statistic improves from 0.60 to 0.80 (p = 0.002)., Conclusions: Alterations of RV function and pulmonary artery pressure normalize, and post-transplantation RV function may provide prognostic data in patients after lung transplantation. Our study is based on a highly and retrospectively selected group. We believe that larger prospective studies are warranted to confirm this result., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Thoracic radiation leads to radiation-associated cardiac disease (RACD), associated with substantial cardiac morbidity and mortality, often requiring complex cardiothoracic surgery. In patients with RACD, along with valvular lesions, the aorto-mitral curtain (AMC, junction between base of anterior mitral leaflet and aortic root) thickness is increased on transthoracic echocardiography. We sought to identify clinical and transthoracic echocardiography predictors of long-term mortality in patients with RACD., Methods: We studied 173 patients with RACD (75% women, 63±14 years, 53% with breast cancer, 27% with Hodgkin lymphoma; mean time from radiation, 18±12 years), who underwent cardiothoracic surgery (26% redo) between 2000 and 2003. Clinical, transthoracic echocardiography (along with AMC), and surgical variables were recorded. Preoperative EuroSCORE and all-cause mortality were recorded., Results: Mean left ventricular ejection fraction, right systolic ventricular pressure, and AMC thickness were 0.49±0.13, 41±15 mm Hg, and 0.54±0.2 cm, respectively. Fifty-one percent of patients had II+ mitral regurgitation or greater, 29% patients had II+ aortic regurgitation or greater, 23% patients had severe aortic stenosis, and 34% patients had II+ tricuspid regurgitation or greater. In 7.6±3 years of follow-up, there were 95 (55%) deaths, with a 30-day mortality rate of only 7 (4%). Absence of β-blockers (hazard ratio, 0.49; 95% confidence interval, 0.31 to 0.79), aspirin (hazard ratio, 0.53; 95% confidence interval, 0.33 to 0.84), higher EuroSCORE (hazard ratio, 1.11; 95% confidence interval, 1.02 to 1.21), and greater AMC thickness (hazard ratio, 5.75; 95% confidence interval, 1.57 to 21.03; all p<0.01) independently predicted mortality. Aorto-mitral curtain thickness of at least 0.6 cm was associated with significantly increased mortality., Conclusions: Patients with RACD undergoing cardiothoracic surgery have high long-term mortality, which is independently predicted by AMC thickness, a higher preoperative risk score, and lack of cardioprotective medications., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Because mitral valve dysfunction in adults with Marfan syndrome is poorly characterized, this study compares mitral valve pathophysiology and morphology with that of myxomatous mitral disease, documents types of mitral valve operations, and assesses long-term survival and durability of mitral valve surgery in Marfan patients., Methods: From May 1975 to June 2000, 27 adults with Marfan syndrome underwent mitral valve surgery. Their valve pathophysiology and morphology was compared with that of 119 patients with myxomatous mitral disease undergoing surgery from September 1995 to March 1999. Survival and repair durability were assessed at follow-up., Results: Compared with myxomatous disease patients, Marfan patients had less posterior leaflet prolapse (44% versus 70%, p = 0.01), more bileaflet (44% versus 28%, p = 0.09) and anterior leaflet prolapse (11% versus 3%, p = 0.07), and presented earlier for surgery (age 41 +/- 12 years versus 57 +/- 13, p < 0.0001). Marfan patients had longer and thinner leaflets. Mitral valve repair was performed less frequently in Marfan (16 of 27, 59%) than myxomatous disease patients (112 of 119, 94%). There were no hospital deaths; at 10 years, survival was 80% and freedom from reoperation 96%, with only 1 reoperation among the 16 repairs., Conclusions: Mitral valve pathophysiology and morphology differ between Marfan and myxomatous mitral valve diseases. Valve repair in Marfan patients is durable and gives acceptable long-term results, even in adults who present with advanced mitral valve pathology. With increasing use of the modified David reimplantation operation and sparing of the aortic valve, mitral valve repair is a greater imperative, particularly since we have not had to reoperate on any Marfan patients with reimplantations.

Mitral valve prolapse is a common valvular abnormality that is the most common cause of severe non-ischaemic mitral regurgitation in the USA. The overall prognosis of patients with mitral valve prolapse is excellent, but a small subset will develop serious complications, including infective endocarditis, sudden cardiac death, and severe mitral regurgitation. We present a comprehensive review of mitral valve prolapse, examining normal mitral anatomy, the clinical and echocardiographic features of mitral valve prolapse, and the pathophysiology and genetics of the disorder. We discuss the contemporary management of both asymptomatic and symptomatic prolapse, with particular attention to the timing and technique of surgical repair. We conclude that echocardiography is the method of choice for diagnosing mitral valve prolapse, that clinical and echocardiographic features can predict which patients with prolapse are at highest risk for complications, and that mitral valve repair is the treatment of choice for symptomatic prolapse.

Background: Native valve endocarditis is frequently managed with antibiotics alone, but prosthetic valve endocarditis usually requires an early operation. What is the best treatment of endocarditis after mitral valve repair?, Methods: From 1986 to 2000, 22 patients were treated for endocarditis affecting a previously repaired mitral valve. Causes of mitral valve dysfunction that led to repair were degenerative (11 patients), ischemic (5 patients), endocarditic (3 patients), rheumatic (2 patients), and functional (1 patient). Endocarditis was active in 21 patients and healed in 1. Interval from initial mitral valve repair to onset of endocarditis ranged from 1 week to 10.3 years (median, 6 months). Pathology included leaflet vegetation (15), annuloplasty vegetation (4), leaflet perforation (5), and abscess (3). Mean follow-up was 3.9 +/- 3.3 years., Results: Fifteen patients underwent repeat mitral valve operations with freedom from mitral valve reoperation of 65%, 41%, and 26% at 30 days, 1 year, and 5 years after onset of endocarditis. After a high early hazard, risk of reoperation fell to 10.8% per year. Seven patients, all with a leaflet vegetation, were treated with antibiotics alone. Antibiotics eradicated infection in all; however all had mitral regurgitation 2+ to 4+. Survival was 96%, 74%, and 68% at 30 days, 1 year, and 5 years. Endocarditis recurred in 1 patient (92% free of event)., Conclusions: Most patients that have endocarditis develop after mitral valve repair require reoperation. However if infection is limited to a leaflet, early reoperation may be unnecessary because antibiotics alone can eradicate infection.

Transesophageal echocardiography (TEE) provides excellent delineation of ventricular function in the ambulatory and critical settings. Major indications include the acutely ill patient with suboptimal images with other techniques and the intraoperative assessment of patients undergoing cardiac surgery and of cardiac patients undergoing noncardiac surgery. The methodology of quantification of ventricular function is quite accurate, though it has inherent limitations. Newer technologies, such as edge enhancement techniques, three-dimensional acquisition, and contrast agents, all have the potential to improve evaluation of ventricular function with TEE. Stress imaging with TEE is possible with dobutamine and with pacing techniques. This is sage and accurate, and it is indicated in patients, such as the morbidly obese, who are impossible to image by other methods.