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The current guidelines recommend intervention in severe degenerative mitral regurgitation (MR) in symptomatic patients or asymptomatic patients with left ventricular dilatation or dysfunction. The insidious onset of symptoms may mean that patients do not report their symptoms. The role of systematic exercise testing for symptoms in MR is not clearly defined. A total of 97 patients with moderate to severe asymptomatic MR underwent exercise echocardiography combined with cardiopulmonary exercise testing. The predictors of exercise-induced dyspnea, symptom-free survival, and mitral valve intervention were identified. A total of 18 patients (19%) developed limiting dyspnea on exercise. Spontaneous symptom-free survival at 24 months was significantly higher in those without exercise-induced symptoms than those with exercise-induced symptoms, p <0.0001. The only independent predictors of spontaneous symptoms at 2 years were effective regurgitant orifice area (odds ratio 27.45, 95% confidence interval [CI] 1.43 to 528.40, p = 0.03) and exercise-induced symptoms (odds ratio 11.56, 95% CI 1.71 to 78.09, p = 0.01). The only independent predictor of surgery was indexed left ventricular systolic volumes (odds ratio 1.17, 95% CI 1.04 to 1.30, p = 0.006). Where only the patients who underwent surgery due to symptoms were included, the only independent predictor was exercise-induced symptoms (odds ratio 13.94, 95% CI 1.39 to 140.27, p = 0.025). In conclusion, in patients with primary asymptomatic degenerative MR, 1/5 develop revealed symptoms during exercise. This predicts a subsequent development of spontaneous symptoms and mitral valve intervention due to symptoms., Competing Interests: Declaration of Competing Interest Dr. Petersen reports a relation with Circle Cardiovascular Imaging Inc., Calgary, Alberta, Canada (SEP) that includes consulting or advisory. The remaining authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The effects of catheter ablation on exercise tolerance and quality of life in patients with atrial fibrillation (AF) have been reported. We assessed cardiac function in more detail using the leg positive pressure (LPP) technique and found that contractile reserve is particularly important in relation to exercise tolerance and prognosis. In this study, we used the LPP technique to examine changes in contractile reserve immediately after ablation and 6 months later. We prospectively enrolled patients who underwent catheter ablation for AF at 2 institutes. We performed LPP stress echocardiography 2 to 3 days after (FU-1) and 6 months after (FU-2) ablation to examine changes in cardiac function indexes. The primary end point was improvement in contractile reserve. Ultimately, 109 patients (mean age 67.4 ± 9.6 years; 70% men) underwent 2 sessions of LPP stress echocardiography. The median CHA 2 DS 2 -VAS C score was 2 (interquartile range 13). From FU-1 to FU-2, the change in the stroke volume index after the LPP maneuver increased in patients with paroxysmal and persistent AF with low CHA 2 DS 2 -VAS C scores (both p <0.05). Regardless of AF subtype, contractile reserve at FU-2 improved in patients with low CHA 2 DS 2 -VAS C scores compared with that at FU-1. In contrast, patients with high CHA 2 DS 2 -VAS C scores had no change. In conclusion, patients with AF with a low CHA 2 DS 2 -VAS C score had improved contractile reserve after ablation, whereas patients with high scores did not show any improvement. Aggressive interventions in patients with high scores may lead to better management after catheter ablation., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Heart rate reserve (HRR) during physical or pharmacological stress is a sign of cardiac autonomic function and sympathetic reserve, but it can be reduced during exercise for confounders such as poor motivation, drugs or physical fitness. In this study we sought to assess the prognostic meaning of HRR during dipyridamole stress echocardiography (DSE) in patients with abnormal chronotropic response to exercise. From 2004 to 2019, we prospectively acquired and retrospectively analyzed 379 patients (age 62 ± 11 years; ejection fraction 60 ± 5%) with suspected (n = 243) or known (n = 136) chronic coronary syndromes, referred to DSE for chronotropic incompetence during upright bicycle exercise-electrocardiography test defined as HRR used [(peak HR - rest HR) / (220 - age) - rest HR] ≤80% in patients off and ≤62% in patients on beta-blockers. All patients were in sinus rhythm and underwent DSE (0.84 mg/kg) within 3 months of exercise testing. During DSE, age-independent HRR (peak/rest HR) ≤1.22 was considered abnormal. All patients were followed-up. All-cause death was the only outcome measure. HRR during DSE was normal in 275 (73%) and abnormal in 104 patients (27%). During a follow-up of 9.0 ± 4.2 years, 67 patients (18%) died. The 15-year mortality rate was 23% in patients with normal and 61% in patients with abnormal HRR (p < 0.0001). At multivariable analysis a blunted HRR during DSE was an independent predictor of outcome (hazard ratio 2.01, 95% confidence intervals 1.23-3.29; p = 0.005) with age and diabetes, while neither inducible ischemia nor ongoing beta-blocker therapy were significant predictors. In conclusion, a blunted HRR during DSE predicts a worse survival in patients with chronotropic incompetence during exercise test. HRR during DSE is an appealingly simple biomarker of cardiac autonomic dysfunction independent of imaging, exercise and beta-blocker therapy., (Copyright © 2021. Published by Elsevier Inc.)

Patients with diabetes mellitus (DM) frequently present reduced exercise capacity. We aimed to explore the extent to which peripheral extraction relates to exercise capacity in asymptomatic patients with DM. We prospectively enrolled 98 asymptomatic patients with type-2 DM (mean age of 59 ± 11 years and 56% male sex), and compared with 31 age, sex and body mass index-matched normoglycemic controls. Cardiopulmonary exercise testing with resting followed by stress echocardiography was performed. Exercise response was assessed using peak oxygen uptake (peak VO 2 ) and ventilatory efficiency was measured using the slope of the relationship between minute ventilation and carbon dioxide production (VE/VCO 2 ). Peripheral extraction was calculated as the ratio of VO 2 to cardiac output. Cardiac function was evaluated using left ventricular longitudinal strain, E/e', and relative wall thickness. Among patients with DM, 26 patients (27%) presented reduced percent-predicted-peak VO 2 (<80%) and 18 (18%) presented abnormal VE/VCO 2 slope (>34). There was no significant difference in peak cardiac output; however, peripheral extraction was lower in patients with DM compared to controls. Higher peak E/e' (beta = -0.24, p = 0.004) was associated with lower peak VO 2 along with age, sex and body mass index (R 2  = 0.53). A cluster analysis found left ventricular longitudinal strain, E/e', relative wall thickness and peak VO 2 in different clusters. In conclusion, impaired peripheral extraction may contribute to reduced peak VO 2 in asymptomatic patients with DM. Furthermore, a cluster analysis suggests that cardiopulmonary exercise testing and echocardiography may be complementary for defining subclinical heart failure in patients with DM., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Evaluation of chest pain in the emergency department (ED) frequently employs a noninvasive strategy, including coronary computed tomography angiography (CCTA), stress echocardiography (SE), or myocardial perfusion imaging (MPI). We sought to report the real-world experience of utilizing CCTA compared with SE and MPI at an urban hospital ED. We conducted a retrospective cohort study of consecutively enrolled patients presenting with chest pain who had normal or nondiagnostic electrocardiogram (ECG), negative initial troponin-T, at least intermediate risk based on modified Diamond-Forrester criteria, and who underwent CCTA, SE, or MPI based on their individual test eligibility criteria. The primary outcome was ED discharge time. Secondary outcomes included test utilization and 30-days rehospitalization rates. The 2,143 patients who were included (mean age was 56 ± 12 years; 55% women) utilization rate (test performed/eligible) was lower for CCTA (n = 354/1,329) and MPI (n = 530/1,435) compared with SE (n = 1,259/1,650), p <0.001. Mean ED discharge times for both CCTA and SE were 12.5 ± 7.4 versus 16 ± 7.3 hours for MPI (p <0.0001). Patients with SE and CCTA were less likely to undergo coronary angiography (29%, 25%, vs 52% for MPI). There was a 1% cardiac-related 30-days rehospitalization rate in the CCTA group versus 1% in SE and 3% in the MPI group (p <0.01). In conclusion, CCTA and SE were associated with faster ED discharge and lower frequency of diagnostic coronary angiography. Notwithstanding its clinical utility, CCTA was underutilized at our large urban ED setting., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In patients in sinus rhythm, a blunted heart rate reserve (HRR) during dipyridamole stress echocardiography (SE) is a prognostically unfavorable sign of cardiac autonomic dysfunction. In this study we sought to assess the prognostic meaning of HRR in patients with permanent atrial fibrillation (AF). The study population was made by 301 patients (176 men, age 73 ± 8 years) with suspected (n = 200) or known (n = 101) coronary artery disease and permanent AF who underwent high-dose dipyridamole SE. HRR was calculated on an average of 5 consecutive beats as the peak/rest ratio of HR from 12-lead EKG. During a median follow-up time of 77 months (first quartile 44, third quartile 115 months), 111 (37%) patients died. Receiver operating characteristics analysis identified HRR ≤1.17 as the best predictor of mortality. At multivariable analysis, HRR ≤1.17 (HR 1.75, 95% CI 1.17 to 2.62; p = 0.006) independently predicted mortality together with age (HR 1.09, 95% CI 1.06 to 1.13; p <0.0001), rest wall motion score index (HR 1.69, 95% CI 1.01 to 2.83; p = 0.04), and systemic hypertension (HR 1.76, 95% CI 1.06 to 3.00; p = 0.04). The annual mortality was 5.1% in the overall population, 7.0% in the 140 (46%) patients with abnormal HRR and 3.5% in the 161 (54%) patients with normal HRR. The 8-year mortality was 48% in patients with abnormal HRR and 18% in those with normal HRR (p <0.0001). In conclusion, patients with suspected or known coronary artery disease with permanent AF with a blunted HRR have an increased mortality. HRR outweighs inducible ischemia for prediction of survival. The assessment of HRR should become an integral part of dipyridamole SE reading also in AF., (Copyright © 2020. Published by Elsevier Inc.)

Clinical risk stratification for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HC) employs rules derived from American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines or the HCM Risk-SCD model (C-index ∼0.69), which utilize a few clinical variables. We assessed whether data-driven machine learning methods that consider a wider range of variables can effectively identify HC patients with ventricular arrhythmias (VAr) that lead to SCD. We scanned the electronic health records of 711 HC patients for sustained ventricular tachycardia or ventricular fibrillation. Patients with ventricular tachycardia or ventricular fibrillation (n = 61) were tagged as VAr cases and the remaining (n = 650) as non-VAr. The 2-sample ttest and information gain criterion were used to identify the most informative clinical variables that distinguish VAr from non-VAr; patient records were reduced to include only these variables. Data imbalance stemming from low number of VAr cases was addressed by applying a combination of over- and undersampling strategies. We trained and tested multiple classifiers under this sampling approach, showing effective classification. We evaluated 93 clinical variables, of which 22 proved predictive of VAr. The ensemble of logistic regression and naïve Bayes classifiers, trained based on these 22 variables and corrected for data imbalance, was most effective in separating VAr from non-VAr cases (sensitivity = 0.73, specificity = 0.76, C-index = 0.83). Our method (HCM-VAr-Risk Model) identified 12 new predictors of VAr, in addition to 10 established SCD predictors. In conclusion, this is the first application of machine learning for identifying HC patients with VAr, using clinical attributes. Our model demonstrates good performance (C-index) compared with currently employed SCD prediction algorithms, while addressing imbalance inherent in clinical data., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

The purpose of this study was to determine the relation between liver histology, exercise tolerance, and diastolic function in patients with nonalcoholic fatty liver disease (NAFLD). Myocardial remodeling and diastolic dysfunction have been associated with NAFLD. However, its physiological impact and relationship to the histological severity of NAFLD is not known. Cardiopulmonary exercise testing and stress echocardiography was performed in subjects with biopsy-confirmed NAFLD. Maximal aerobic exercise capacity (peak oxygen consumption [VO 2 ]) was related to diastolic function (mitral annulus Doppler velocity e' and ratio of early diastolic filling pressure [E] to e' [E/e']) at rest and peak exercise. Autonomic dysfunction was determined from heart rate recovery after exercise. Independent predictors of cardiac function and exercise capacity were identified by multivariable regression. Thirty-six subjects (nonalcoholic fatty liver [NAFL  =  15], nonalcoholic steatohepatitis [NASH  =  21]) were enrolled. NASH was associated with impaired exercise capacity compared with NAFL (median peak VO 2 17.0 [15.4, 18.9] vs 19.9 [17.4, 26.0], p  =  001); pVO 2 declined with increasing fibrosis (F0  =  22.5, F1  =  19.9, F2  =  19.0, F3  =  16.6 ml·kg -1 ·min -1 ; p  =  0.01). Similarly, E/e' during exercise increased progressively with increasing fibrosis (F0  =  5.6, F1  =  6.5, F2  =  8.7, F3  =  9.8; P  =  0.02). Finally, heart rate recovery, a marker of autonomic function, was blunted in those with higher fibrosis stages (F0  =  25 [20, 30], F1  =  23 [17.5, 27.0], F2  =  17 [11.8, 21.5], F3  =  11 [8.5, 18.0] beats per minute; p <0.01). Fibrosis was an independent predictor of these functional outcomes. In conclusion, NASH is associated with impaired exercise capacity and diastolic dysfunction compared with NAFL. The severity of impairment is directly related to the severity of fibrosis stage in precirrhotic stages of NAFLD., (Copyright © 2018. Published by Elsevier Inc.)

There are few data on the utility of physician selection of cardiac tests, including no-test, in a chest pain unit (CPU) to rule out acute coronary syndrome in low-risk patients without a history of coronary artery disease. We analyzed consecutive low-risk patients admitted to our CPU between 2012 and 2014 and determined the proportion of patients selected for testing, the type of initial cardiac test selected, and the incidence of major adverse cardiac events (MACEs) at 30 days and 6 months. The study group comprised 619 patients: mean age 57 years (27 to 92), 332 women (54%), and 360 (58%) with multiple cardiac risk factors. Cardiac testing included 283 no-test (46%); 179 exercise treadmill (29%); 113 myocardial perfusion stress scintigraphy (18%); <10% each for exercise stress echocardiography and coronary angiography. Testing was negative in 296 (88%), nondiagnostic in 30 (9%), and positive in 10 patients (3%). There were no MACEs at 30 days in any patients, and at 6 months, MACEs were 5 (1.1%). Length of stay was less in no-test than in tested patients (5.4 hours vs 9.8 hours, p <0.0001), and there was no difference in incidence of MACE at 6 months in no-test vs tested patients (2 MACEs vs 3 MACEs). Physician selection of cardiac tests, including no-test, promptly identified patients at low risk of acute coronary syndrome who could be safely and rapidly discharged from the CPU. Exclusion of cardiac testing shortened length of stay and was not associated with increase in MACE at 6 months., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Stress testing is endorsed by the American College of Cardiology/American Heart Association Appropriate Use Criteria to identify appropriate candidates for Chronic Total Occlusion (CTO) Percutaneous Coronary Intervention (PCI). However, the relation between stress test risk classification and health status after CTO PCI is not known. We studied 449 patients in the 12-center OPEN CTO registry who underwent stress testing before successful CTO PCI, comparing outcomes of patients with low-risk (LR) versus intermediate to high-risk (IHR) findings. Health status was assessed using the Seattle Angina Questionnaire Angina Frequency (SAQ AF), Quality of Life (SAQ QoL), and Summary Scores (SAQ SS). Stress tests were LR in 40 (8.9%) and IHR in 409 (91.1%) patients. There were greater improvements on the SAQ AF (LR vs IHR 14.2 ± 2.7 vs 23.3 ± 1.3 points, p <0.001) and SAQ SS (LR vs IHR 20.8 ± 2.3 vs 25.4 ± 1.1 points, p = 0.03) in patients with IHR findings, but there was no difference between groups on the SAQ QoL domain (LR vs IHR 24.8 ± 3.4 vs 27.3 ± 1.6 points, p = 0.42). We observed large health status improvements after CTO PCI in both the LR and IHR groups, with the greatest reduction in angina among those with IHR stress tests. Although patients with higher risk studies may experience greater reduction in angina symptoms, on average, patients with LR stress tests also experienced large improvements in symptoms after CTO PCI, suggesting patients with refractory symptoms should be considered appropriate candidates for CTO PCI regardless of stress test findings., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Functional capacity in exercise stress testing is an independent predictor of cardiac events. Routine use of nuclear perfusion imaging increases radiation burden and cost. Our goal was to assess the clinical utility of exercise functional capacity with stress electrocardiogram (ECG) as an adjunct in predicting the presence of high-risk obstructive coronary artery disease (CAD) on diagnostic coronary angiography. We performed a retrospective study of patients who underwent exercise stress testing for the evaluation of chest pain and underwent diagnostic coronary angiography within the subsequent 3 months. High-risk CAD was defined as coronary artery diameter stenosis of ≥70% in the proximal left anterior descending artery, ≥70% diameter stenosis in 3 major epicardial arteries, or ≥50% diameter stenosis in the left main artery. Univariable and multivariable analyses were performed to identify predictors of high-risk CAD. Of the 412 patients, 105 (25%) had high-risk CAD on coronary angiography. On multivariate logistic regression, we found that positive stress ECG, abnormal stress imaging, left ventricular ejection fraction, and male gender were independent predictors of high-risk CAD. The strongest predictor was positive stress ECG (hazard ratio 3.16, 95% confidence interval 1.90 to 5.27, p <0.001). Functional capacity measures alone were not independent predictors of high-risk CAD. Achieving ≥10 METs with a negative stress ECG resulted in 94% sensitivity and 97% negative predictive value in identifying high-risk CAD. This supports the strategy for provisional use of myocardial perfusion imaging in patients with low functional capacity and/or abnormal stress ECG to minimize cost and radiation exposure., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The approach to managing asymptomatic or questionably symptomatic patients for aortic stenosis is difficult. We aimed to determine whether cardiopulmonary exercise testing (CPET) is prognostically useful in such patients. Patients judged asymptomatic or questionably symptomatic for aortic stenosis with aortic valve area index <0.6 cm 2 /m 2 and left ventricular ejection fraction ≥0.50 were managed conservatively provided they had either (group 1) normal peak oxygen consumption and peak oxygen pulse (>83% and >95% of the predicted values, respectively) or (group 2) subnormal peak oxygen consumption or peak oxygen pulse but with CPET data pointing to pathologies other than hemodynamic compromise from aortic stenosis. Increase in systolic blood pressure <20 mm Hg, ST depression ≥2 mm, or symptoms during the exercise test were allowed. Unexpected events included cardiac death or hospitalization with heart failure in patients who had not been recommended valve replacement. The median age of the study population (n = 101) was 75 years (interquartile range 65 to 79 years), and 67% were judged questionably symptomatic. During a follow-up at 24 ± 6 months, the rate of unexpected cardiac death and unexpected hospitalization with heart failure was 0% and 6.0%, respectively. All-cause mortality was 4.0% compared with 8.0% in the age- and gender-matched population. For group 1, 26 of 70 (37.1%) succumbed to cardiac death, or were hospitalized because of heart failure, or underwent valve replacement, and for group 2 this was 12 of 31 (38.7%). In conclusion, if CPET does not indicate a significant hemodynamic compromise because of aortic stenosis, an initially conservative strategy results in a good prognosis and an acceptable event rate., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

Patients undergoing orthotopic liver transplantation have high rates of cardiac morbidity and mortality. Although guidelines recommend noninvasive stress testing as part of the preoperative evaluation, little data have evaluated clinical outcomes following orthotopic liver transplantation. A retrospective study at 2 high-volume liver transplantation centers was performed. All patients undergoing noninvasive stress testing (myocardial perfusion imaging [MPI] or dobutamine stress echocardiography [DSE]) over a 5-year period were included. Descriptive analyses, including clinical outcomes and perioperative and postoperative ischemic events, were performed. Comparisons were made between subsets of patients within each stress modality based on abnormal versus normal results. A total of 506 patients were included, of which 343 underwent DSE and 163 MPI. Few patients had abnormal results, with 19 (5.5%) in the DSE group and 13 (8%) in the MPI group. Perioperative and postoperative cardiac complications were low (n = 20, 5.8% and n = 3, 0.9% in DSE group and n = 15, 9.2% and n = 3, 1.8% in MPI group). Comparisons between abnormal versus normal findings showed a trend toward periprocedural cardiac complications in the abnormal DSE group (n = 3, 15.8% vs n = 17, 5.25%; p = 0.09) with no difference in 6-month postprocedural complications (n = 0 vs n = 3, 0.9%; p = 1.0). In the MPI group, a trend toward periprocedural ischemic complications (n = 3, 23.1% vs n = 12, 8%; p = 0.1) was noted with no difference in 6-month postprocedural complications (n = 0 vs n = 3, 2%; p = 1.0). In conclusion, our study found a significantly lower than reported cardiac event rate. In addition, it demonstrated that ischemic cardiac events are uncommon in patients with normal stress testing., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Combining echocardiography and cardiopulmonary stress testing allows noninvasive assessment of hemodynamics, and oxygen extraction (A-VO 2 difference). We evaluated mechanisms of effort intolerance in patients with heart failure with borderline (40% to 49%) left ventricular ejection fraction (EF) (HF and Borderline Ejection fraction). We included 89 consecutive patients with HF and Borderline Ejection fraction (n = 25; 63.6 ± 14 years, 64% men), control subjects (n = 22), patients with HF with preserved EF (n = 26; EF ≥50%), and patients with HF with reduced EF (n = 16; <40%). Various echo parameters (left ventricular volumes, EF, stroke volume, mitral regurgitation [MR] volume, e', right ventricle end-diastolic area, and right ventricle end-systolic area), and ventilatory or combined parameters (peak oxygen consumption [VO 2 ] and A-VO 2 difference) were measured at 4 predefined activity stages. Effort-induced functional MR was frequent and more prevalent in HF and Borderline Ejection fraction than in all the other types of HF. In multivariable analysis heart rate response (p <0.0001), A-VO 2 difference (p = 0.02), stroke volume (p = 0.002), and right ventricle end-systolic area were the only independent predictors of exercise capacity in HF and Borderline Ejection fraction but peak EF was not. In HF and Borderline Ejection fraction exercise intolerance is predominantly due to chronotropic incompetence, peripheral factors, and limited stroke volume reserve, which are related to right ventricle dysfunction and functional MR but not to left ventricular ejection fraction. Combined testing can be helpful in determining mechanisms of exercise intolerance in HF and Borderline Ejection fraction., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The aim of this study was to compare clinically relevant cardiovascular outcomes and downstream resource utilization associated with stress echocardiography (SE) and myocardial perfusion imaging (MPI) in emergency department patients with low-risk chest pain. This was a retrospective analysis of health insurance claims data for a national sample of privately insured patients over the period January 1 to December 31, 2011. Subjects were selected who presented to the emergency department with a primary or secondary diagnosis of chest pain and underwent either SE or MPI. The primary end points were the percentage of patients in each group who underwent downstream cardiac catheterization, revascularization, repeat noninvasive testing, return emergency department visit with chest pain, and hospitalization for myocardial infarction. The mean length of follow-up was 190 days in both groups. Overall, 48,202 patients or 24,101 propensity-matched pairs were included in the final analysis. Compared with SE, MPI was associated with significantly higher odds of subsequent cardiac catheterization (adjusted odds ratio [AOR] 2.15; 95% confidence interval [CI] 1.99 to 2.33) and revascularization procedures (AOR 1.58; 95% CI 1.36 to 1.85) and repeat emergency department visits (AOR 1.14; 95% CI 1.11 to 1.19). The odds of repeat testing and myocardial infarction did not differ between groups. The average cost of downstream care was significantly higher in the MPI group ($2,193.80 vs $1,631.10, p <0.0001). According to the a priori rules specified for this comparative analysis, SE is more effective than MPI for privately insured patients who present to the emergency department with chest pain. In conclusion, these findings demonstrate the importance of assessing diagnostic tests based on how they affect hard end points because identification of disease, in and of itself, may not confer any clinical advantage., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The prognostic value of dobutamine stress echocardiography (DSE) at >10-year follow-up is unknown. The aim of this study was to assess the very long-term prognostic value of DSE in a high-risk cohort of patients with known or suspected coronary artery disease. This prospective, single-center study included 3,381 patients who underwent DSE from January 1990 to January 2003. Two-dimensional echocardiographic images were acquired at rest, during dobutamine stress, and during recovery. Follow-up events were collected and included overall mortality, cardiac death, nonfatal myocardial infarction, and revascularization. The incremental value of DSE in the prediction of selected end points was evaluated using multivariate Cox proportional hazard analysis. During a mean follow-up of 13 ± 3.2 years (range 7.3 to 20.5 years), there were 1,725 deaths (51%), of which 1,128 (33%) were attributed to cardiac causes. Patients with an abnormal DSE had a higher mortality rate (44% vs 35% at 15-year follow-up, p <0.001) than those with a normal DSE. When comparing echocardiographic variables at rest to variables at maximum dose dobutamine, the chi-square of the test improved from 842 to 870 (p <0.0001) and from 684 to 740 (p <0.0001) for all-cause mortality and cardiac death, respectively. DSE provided incremental value in predicting all-cause mortality, cardiac death, and hard cardiac events. There seems, however, to be a "warranty period" of approximately 7 years, when the survival curves of a normal and abnormal DSE no longer diverge., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The impact of baseline exercise capacity on clinical outcomes in patients with stable ischemic heart disease randomized to an initial strategy of optimal medical therapy (OMT) with or without percutaneous coronary intervention (PCI) in the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial has not been studied. A post hoc analysis was performed in 1,052 patients of COURAGE (PCI + OMT: n = 527, OMT: n = 525) who underwent exercise treadmill testing at baseline. Patients were categorized into 2 exercise capacity groups based on metabolic equivalents (METs) achieved during baseline exercise treadmill testing (<7 METs: n = 464, ≥7 METs: n = 588) and were followed for a median of 4.6 years. The primary composite end point of death or myocardial infarction was similar in the PCI + OMT group and the OMT group for patients with exercise capacity <7 METs (19.1% vs 16.1%, p = 0.31) and ≥7 METs (13.3% vs 10.3%, p = 0.27). After adjusting for baseline covariates, the hazard ratio (99% confidence interval) for the primary end point for the PCI + OMT group versus the OMT group was 1.42 (0.90 to 2.23, p = 0.05) and for the exercise capacity subgroups of ≥7 METs and <7 METs was 0.75 (0.46 to 1.22, p = 0.13). There was no statistically significant interaction between the original treatment arm allocation (PCI + OMT vs OMT) and baseline exercise capacity. In conclusion, there was no difference in the long-term clinical outcomes in patients with exercise capacity <7 METs compared with ≥7 METs, irrespective of whether they were assigned to initial PCI. Patients with exercise capacity <7 METs did not derive a proportionately greater clinical benefit from PCI + OMT compared with those patients who received OMT alone., (Published by Elsevier Inc.)

Patients with nonobstructive hypertrophic cardiomyopathy (HC) are considered low risk, generally not requiring aggressive intervention. However, nonobstructive and labile-obstructive HC have been traditionally classified together, and it is unknown if these 2 subgroups have distinct risk profiles. We compared cardiovascular outcomes in 293 patients HC (96 nonobstructive, 114 labile-obstructive, and 83 obstructive) referred for exercise echocardiography and magnetic resonance imaging and followed for 3.3 ± 3.6 years. A subgroup (34 nonobstructive, 28 labile-obstructive, 21 obstructive) underwent positron emission tomography. The mean number of sudden cardiac death risk factors was similar among groups (nonobstructive: 1.4 vs labile-obstructive: 1.2 vs obstructive: 1.4 risk factors, p = 0.2). Prevalence of late gadolinium enhancement (LGE) was similar across groups but more non-obstructive patients had late gadolinium enhancement ≥20% of myocardial mass (23 [30%] vs 19 [18%] labile-obstructive and 8 [11%] obstructive, p = 0.01]. Fewer labile-obstructive patients had regional positron emission tomography perfusion abnormalities (12 [46%] vs nonobstructive 30 [81%] and obstructive 17 [85%], p = 0.003]. During follow-up, 60 events were recorded (36 ventricular tachycardia/ventricular fibrillation, including 30 defibrillator discharges, 12 heart failure worsening, and 2 deaths). Nonobstructive patients were at greater risk of VT/VF at follow-up, compared to labile obstructive (hazed ratio 0.18, 95% confidence interval 0.04 to 0.84, p = 0.03) and the risk persisted after adjusting for age, gender, syncope, family history of sudden cardiac death, abnormal blood pressure response, and septum ≥3 cm (p = 0.04). Appropriate defibrillator discharges were more frequent in nonobstructive (8 [18%]) compared to labile-obstructive (0 [0%], p = 0.02) patients. In conclusion, nonobstructive hemodynamics is associated with more pronounced fibrosis and ischemia than labile-obstructive and is an independent predictor of VT/VF in HC., (Copyright © 2015 Elsevier Inc. All rights reserved.)

We assessed the left ventricular (LV) contractile reserve in young adults with repaired coarctation of the aorta and interrupted aortic arch by determination of LV force-frequency relation (FFR). Eighteen (7 men) patients aged 24.2 ± 5.4 years and 20 (9 men) healthy controls were studied. Blood pressures in the right arm were measured by oscillometry. Transmitral early (E) and late (A) diastolic velocities, tissue Doppler-derived mitral annular systolic (sm), early diastolic (em) and late diastolic (am) velocities, and myocardial isovolumic acceleration (IVA) were measured. The LV FFR and average slope were derived from the IVA measured at different heart rates during supine bicycle exercise. Blood pressures at rest were similar between patients and controls (all p >0.05). At baseline, patients compared with controls had significantly greater E velocity, E/A and E/em ratios, and lower sm and em velocities (all p <0.05) but similar IVA (p = 0.18). At submaximal exercise, diastolic (p = 0.001) and mean (p = 0.003) blood pressures became significantly higher in patients than controls, sm (p = 0.001) and em (p <0.001) velocities remained reduced, whereas the IVA became lower (p <0.001). The weighted average FFR was flattened (p <0.001), and average FFR slope was lower (p <0.001) in patients compared with controls. The average FFR slope correlated negatively with the magnitude of exercise-induced increase in systolic (r = -0.32, p = 0.050), mean (r = -0.41, p = 0.011), and diastolic (r = -0.40, p = 0.013) blood pressures. In conclusion, young adults after coarctation of the aorta and interrupted aortic arch repair exhibit reduced LV contractile reserve, which is related to the blood pressure response during exercise stress., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Age, creatinine, and ejection fraction (ACEF) score predict clinical outcomes in patients who underwent elective percutaneous coronary intervention (PCI) of nonocclusive coronary stenoses. We aimed at assessing the prognostic value of the ACEF score in patients who underwent successful PCI of chronic total occlusion (CTO). ACEF score was calculated in 587 patients treated with PCI of CTO: successful in 433 (74%; success group) and failed in 154 patients (26%; failure group). Patients were divided in ACEF tertiles: first <0.950, second from 0.950 to 1.207, and third ACEF tertile >1.207. Major adverse cardiac events (MACE = overall death + nonfatal myocardial infarction + clinically driven target vessel revascularization) were assessed in 558 patients (95%) up to 24 months (8 to 24 months). In success group, higher MACE rate was significantly associated with increasing ACEF tertile (first = 7%, second = 13%, third ACEF = 18%, p = 0.02). MACE-free survival was significantly decreased with increasing ACEF tertile (log-rank 5.58, p = 0.018). In the failure group, lower MACE rate was significantly associated with increasing ACEF tertile (p = 0.041). This was mainly driven by significant decreasing rate of target vessel revascularization along the tertiles (first = 34%, second = 19%, third ACEF = 10%, p = 0.007). Compared with success group, in failure group, MACE rate was significantly higher in the first tertile (p <0.001) and similar in the third tertile (p = 0.59). In conclusion, ACEF score represents a simple tool in the prognostication of patients successfully treated with PCI of CTO and identifies those patients who would not derive any significant clinical harm despite failed percutaneous revascularization of the CTO., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Sleep disordered breathing (SDB) is associated with type 2 diabetes mellitus (T2DM) and cardiovascular disease; however, the contribution of SDB to incident heart failure (HF), coronary artery disease (CAD), and atrial fibrillation (AF) in patients with T2DM is unknown. We followed up 834 consecutive asymptomatic patients with T2DM (age 56 ± 11 years, 369 women) with normal exercise echocardiographic findings for ≤8 years using electronic health records. The demographics, cardiac risk factors, symptoms, diagnoses, and medications were collected at the echocardiography and validated from the electronic health records. SDB was confirmed by a comprehensive sleep evaluation and/or polysomnography before echocardiography. SDB was diagnosed in 188 patients (21%) at baseline; 116 were untreated. During a median follow-up of 4.9 years (interquartile range 3.9 to 6.1), 22 congestive HF, 72 CAD, and 40 AF incident events were observed. In the Cox proportional hazards models, SDB was associated with incident CAD (hazard ratio 1.8, 95% confidence interval 1.1 to 3.0, p = 0.01; adjusted hazard ratio 1.9, 95% confidence interval 1.2 to 3.2, p <0.01) and AF (hazard ratio 2.6, 95% confidence interval 1.4 to 4.7, p = 0.01; adjusted hazard ratio 2.9, 95% confidence interval 1.5 to 5.9, p <0.01). Limiting SDB to only those patients diagnosed using polysomnography (n = 132), SDB was associated with incident CAD (hazard ratio 1.9, 95% confidence interval 1.1 to 3.3, p = 0.03; adjusted hazard ratio 2.2, 95% confidence interval 1.2 to 3.9, p = 0.01) and HF (hazard ratio 2.7, 95% confidence interval 1.1 to 7.0, p = 0.03; adjusted hazard ratio 3.5, 95% confidence interval 1.4 to 9.0, p <0.01). Female gender, age, elevated blood pressure, and left ventricular mass were additional correlates of CAD in those with asymptomatic T2DM. In conclusion, the association of SDB with incident CAD, AF, and HF in patients with T2DM justifies more liberal screening for SDB in patients with T2DM, realizing that SDB is a potentially modifiable risk factor., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Diabetic autonomic neuropathy is a possible link between abnormal metabolism in type 2 diabetes mellitus (T2DM) and risk for atrial fibrillation (AF) and heart failure (HF). The aim of this study was to elucidate the association between attenuated heart rate recovery (HRR) and these manifestations of myocardial dysfunction in T2DM. Nine hundred fourteen consecutive patients with T2DM (mean age 56 ± 11 years, 508 men) without diabetes mellitus complications, with negative results on stress echocardiography, were enrolled. Patients with known cardiac disease were excluded. Demographics, clinical assessment, co-morbidities, and insulin use were collected prospectively. The association of HRR with new-onset HF and AF was sought using a Cox proportional-hazards model. There were 47 events (22 HF and 25 AF) during a median follow-up period of 7.8 years. Events were associated with age, exercise capacity, HRR, and left atrial volume index but not with baseline glycosylated hemoglobin, left ventricular mass index, or standard markers of diastolic function. In sequential Cox models for the combined outcomes, the model based on clinical data (age and gender; overall chi-square = 5.5) was not significantly improved by left atrial volume index (chi-square = 8.6, p = 0.10) or maximum METs (chi-square = 8.7, p = 0.07) but was significantly improved by adding HRR (chi-square = 19.7, p = 0.004). In addition, HRR provided significant incremental prognostic value regarding the composite end point (net reclassification improvement 19.2%, p = 0.04; integrated discrimination improvement 1.58%, p = 0.004). In conclusion, the association of HRR with subsequent HF and AF, independent of and incremental to left atrial volume index and other markers of abnormal cardiac structure and function, indicates a role for autonomic neuropathy as the link between metabolic and cardiac risk in patients with T2DM., (Copyright © 2013 Elsevier Inc. All rights reserved.)

This meta-analysis evaluated the optimal noninvasive strategy for cardiac risk assessment of patients >65 years of age with known or suspected coronary artery disease using the available literature. Patients >65 years of age constitute a growing proportion of the population and have higher cardiovascular morbidity and mortality, but an optimal strategy to predict the risk of cardiac events in this group is unknown. A systematic search of MEDLINE was performed for cohort studies of ≥100 patients >65 years old with ≥12 months of follow-up that reported cardiac death and/or nonfatal myocardial infarction after any of stress myocardial perfusion imaging (MPI), stress echocardiography, or exercise tolerance testing (ETT) for known or suspected coronary artery disease. Pooled annualized event rates were calculated for each technique. Summary odds ratios (ORs) between normal and abnormal test results were calculated using a random-effects model. Seventeen studies (MPI 7, stress echocardiography 7, ETT 3) in 13,304 patients (mean age 75.5 years) were included. Abnormal compared to normal stress MPI (OR 11.8, 95% confidence interval [CI] 7.5 to 18.7) and stress echocardiography (OR 3.2, 95% CI 2.6 to 3.9) accurately stratified risk in patients. However, patients with abnormal and normal ETT results had similar cardiac event rates (OR 3.1, 95% CI 0.8 to 11.5). In conclusion, stress imaging with MPI or stress echocardiography effectively stratified risk in patients, whereas ETT alone did not., (Copyright © 2012 Elsevier Inc. All rights reserved.)

We sought to determine whether mitral annular calcium (MAC) is associated with inducible myocardial ischemia and adverse cardiovascular outcomes in ambulatory patients with coronary artery disease (CAD). MAC is associated with cardiovascular disease (CVD) in the general population, but its association with CVD outcomes in patients with CAD has not been evaluated. We examined the association of MAC with inducible ischemia and subsequent cardiovascular events in 1,020 ambulatory patients with CAD who were enrolled in the Heart and Soul Study. We used logistic regression to determine the association of MAC with inducible ischemia and Cox proportional hazards models to determine the association with CVD events (myocardial infarction, heart failure, stroke, transient ischemic attack or death). Models were adjusted for age, gender, race, smoking, history of heart failure, blood pressure, high-density lipoprotein, and estimated glomerular filtration rate. Of the 1,020 participants 192 (19%) had MAC. Participants with MAC were more likely than those without MAC to have inducible ischemia (adjusted odds ratio 2.06, 95% confidence interval 1.41 to 3.01, p = 0.0002). During an average of 6.26 ± 2.11 years of follow-up, there were 310 deaths, 161 hospitalizations for heart failure, 118 myocardial infarctions, and 55 cerebrovascular events. MAC was associated with an increased rate of cardiovascular events (adjusted hazard ratio 1.39, 95% confidence interval 1.08 to 1.79, p = 0.01). In conclusion, we found that MAC was associated with inducible ischemia and subsequent CVD events in ambulatory patients with CAD. MAC may indicate a high atherosclerotic burden and identify patients at increased risk for adverse cardiovascular outcomes., (Published by Elsevier Inc.)

There are conflicting data as to the prevalence of coronary artery disease (CAD) in patients with end-stage liver disease (ESLD) being assessed for liver transplantation (LT). The aims of this study were to compare the prevalence of CAD in patients with alcohol-related versus non-alcohol-related ESLD and to assess the diagnostic utility of dobutamine stress echocardiography (DSE) in predicting angiographically important CAD. Consecutive patients with ESLD being assessed for LT (n = 420, mean age 56 ± 8 years) were identified and divided into groups of those with alcohol-related ESLD (n = 125) and non-alcohol-related ESLD (n = 295). Demographic characteristics, CAD risk factors, results of DSE, and coronary angiographic characteristics were recorded. There were no significant differences in age or CAD risk factors between groups. The incidence of severe CAD (>70% diameter stenosis) was 2% in the alcohol-related ESLD group and 13% in the non-alcohol-related ESLD group (p <0.005). In the 2 groups, the presence of ≥1 CAD risk factor was associated with significant CAD (p <0.05 for all). Absence of cardiac risk factors was highly predictive in ruling out angiographically significant disease (negative predictive value 100% for alcohol-related ESLD and 97% for non-alcohol-related ESLD). DSE was performed in 205 patients. In the 2 groups, DSE had poor predictive value for diagnosing significant CAD but was useful in ruling out patients without significant disease (negative predictive value 89% for alcohol-related ESLD and 80% for non-alcohol-related ESLD). In conclusion, there was a significantly lower prevalence of severe CAD in patients with alcohol-related ESLD. These findings suggest that invasive coronary angiography may not be necessary in this subgroup, particularly in the absence of CAD risk factors and negative results on DSE., (Copyright © 2011 Elsevier Inc. All rights reserved.)

We reviewed patients with normal or near-normal coronary angiograms enrolled in the SPAM contrast stress echocardiographic diagnostic study in which 400 patients with chest pain syndrome of suspected cardiac origin with a clinical indication to coronary angiography were enrolled. Patients underwent dipyridamole contrast stress echocardiography (cSE) with sequential analysis of wall motion, myocardial perfusion, and Doppler coronary flow reserve before elective coronary angiography. Ninety-six patients with normal or near-normal epicardial coronary arteries were screened for the presence of 2 prespecified findings: severely tortuous coronary arteries and myocardial bridging. Patients were divided in 2 groups based on the presence (false-positive results, n = 37) or absence (true-negative results, n = 59) of reversible myocardial perfusion defects during cSE and compared for history and clinical and angiographic characteristics. Prevalence of severely tortuous coronary arteries (35% vs 5%, p <0.001) or myocardial bridging (13% vs 2%, p <0.05) was 7 times higher in patients who demonstrated reversible perfusion defects at cSE compared to those without reversible perfusion defects. No significant differences were found between the 2 groups for the main demographic variables and risk factors. Patients in the false-positive group more frequently had a history of effort angina (p <0.001) and ST-segment depression at treadmill electrocardiography (p <0.001). In conclusion, we hypothesize that patients with a positive myocardial perfusion finding at cSE but without obstructive epicardial coronary artery disease have a decreased myocardial blood flow reserve, which may be caused by a spectrum of causes other than obstructive coronary artery disease, among which severely tortuous coronary arteries/myocardial bridging may play a significant role., (Copyright © 2011 Elsevier Inc. All rights reserved.)

A substantial proportion of patients who meet the current guidelines for cardiac resynchronization therapy (CRT) fail to respond to this pacing modality. Although appropriate patient selection and left ventricular (LV) lead location have been ascribed as determinants of CRT response, the interaction among contractile reserve, dynamics of dyssynchrony, and lead location is not well understood. The present study prospectively evaluated the effect of contractile reserve and dobutamine-induced changes in LV synchrony, in relation to the LV lead location, as predictors of the response to CRT. In the present study, 31 patients were prospectively evaluated and underwent low-dose dobutamine echocardiography. The dobutamine-induced increase in ejection fraction (contractile reserve [CR]) was measured, and the most mechanically delayed segment was identified to classify patients into 2 groups. Group 1 had a CR of >20% and a LV lead position concordant with the mechanically delayed segment. Group 2 included the remaining patients (i.e., low CR, discordant LV lead position, or both). Patients in group 1 were significantly more likely to have an echocardiographic response at 6 months (80% of group 1 vs 29% of group 2, p = 0.018) and had an improved 2-year heart failure hospitalization-free survival rate (90% in group 1 vs 33% in group 2, p = 0.006). In conclusion, low-dose dobutamine echocardiography provides information that can help to predict responders to CRT. The response rates and heart failure hospitalization-free survival were improved in those patients with a CR >20% and an LV lead tip concordant with the most delayed mechanical segment., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Patients with type 2 diabetes mellitus (T2DM) might have subclinical myocardial dysfunction identified at rest or unmasked during exercise. We examined the correlates of the myocardial exercise response in patients with T2DM. Myocardial dysfunction was sought during at rest and exercise echocardiography in 167 healthy patients with T2DM (97 men, 55 ± 10 years). Myocardial ischemia was excluded using stress echocardiography. Standard echocardiography and color tissue Doppler imaging measures (early diastolic tissue velocity [Em], strain, and strain rate) were acquired at baseline and peak stress. The calibrated integrated backscatter was calculated from the at rest parasternal long-axis view. The longitudinal diastolic functional reserve index after exercise was defined as ΔEm [1 - (1/Em(base))]. The clinical, anthropometric, and metabolic data were collected at rest and stress. Subclinical myocardial dysfunction at baseline (n = 24) was independently associated with weight (odds ratio [OR] 1.02, p = 0.04) and hemoglobin A1c (OR 1.36, p = 0.03). This group displayed an impaired exercise response that was independently associated with a reduced exercise capacity (OR 0.84, p = 0.034) and longitudinal diastolic functional reserve index (OR 0.69, p = 0.001). Inducible myocardial dysfunction (stress Em <-9.9 cm/s) was identified after exercise in 70 of the remaining 143 subjects. This finding was associated with calibrated integrated backscatter (OR 1.08, p = 0.04) and lower peak heart rate (OR 0.97, p = 0.002) but not metabolic control. The intensity of the metabolic derangement in patients with T2DM was associated with subclinical at rest myocardial dysfunction, but not with the myocardial exercise response. In conclusion, the association of an abnormal stress response with nonmetabolic factors, including backscatter and blunted peak heart rate, suggests potential roles for myocardial fibrosis and cardiac autonomic neuropathy in patients with nonischemic diabetic heart disease., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The additive prognostic value of coronary flow reserve (CFR) over regional wall motion has been established, but there is more than a binary (normal-abnormal) response in CFR, which can be continuously titrated. We assessed the prognostic value of quartiles of CFR, evaluated by transthoracic Doppler of the left anterior descending coronary artery (LAD), in patients with known or suspected coronary artery disease (CAD). One thousand six hundred twenty patients (1,006 men, 64 +/- 11 years of age) underwent dipyridamole (up to 0.84 mg/kg over 6 minutes) stress echocardiography with CFR evaluation of LAD by Doppler and coronary angiography. Patients were followed up for a median of 19 months. Mean CFR in the entire population was 2.25 +/- 0.65. Stress echocardiogram was positive for ischemia in 480 patients (30%). Obstructive (>or=70% vessel stenosis) CAD at angiography was present in 650 patients (40%). During follow-up, there were 298 events (42 deaths, 73 ST-elevation myocardial infarctions, and 183 non-ST-elevation myocardial infarctions). Patients (n = 399) undergoing revascularization were censored. With the Kaplan-Meier method, the first quartile of CFR (

The purpose of this study was to evaluate the prognostic significance of QRS duration in patients with suspected coronary artery disease (CAD) referred for noninvasive evaluation of myocardial ischemia by dobutamine stress echocardiography. QRS duration is a prognostic marker in patients with previous myocardial infarction and/or heart failure. The relation between QRS duration and outcome of patients without known heart disease has not been evaluated. A total of 1,227 patients (707 men, mean age 61 +/- 14 years) with suspected CAD underwent dobutamine stress echocardiography for evaluation of myocardial ischemia. Patients were followed to determine predictors of cardiac events and to assess the incremental significance of QRS duration compared to clinical and dobutamine stress echocardiographic data. During a mean follow-up of 4.2 +/- 2.4 years, 280 patients (23%) died (129 cardiac deaths), and 60 (5%) had a nonfatal infarction. Annualized cardiac death rates were 2.0% in patients with QRS duration <120 ms and 4.4% in patients with QRS duration >or=120 ms, respectively (p <0.0001). Annualized event rates for cardiac death/nonfatal infarction were 2.8% in patients with QRS duration <120 ms and 4.8% in patients with QRS duration >or=120 ms (p = 0.0001). Multivariate models identified age, male gender, smoking, QRS duration >or=120 ms, and an abnormal dobutamine stress echocardiogram as independent predictors of cardiac death and the combined end point cardiac death/nonfatal infarction. In conclusion, QRS duration is an independent predictor of cardiac death and cardiac death/nonfatal infarction in patients with suspected CAD. This risk is persistent after adjustment for clinical variables, left ventricular function, and myocardial ischemia.

Myocardial deformation parameters are sensitive markers of global left ventricular (LV) systolic function, but their interaction with LV geometry is unknown. We sought to investigate the effect of LV geometry on myocardial deformation and its interaction with coronary artery disease (CAD). A total of 126 patients with normal resting LV function who underwent dobutamine stress echocardiography subsequently underwent coronary angiography within 6 months. Longitudinal myocardial deformation was calculated using tissue Doppler echocardiography. The extent of CAD was identified by quantitative coronary angiography. Patients with an increased relative wall thickness had a significantly lower peak strain rate (SR) and a smaller change in SR with stress, with no differences in the at rest values. Those with CAD, had significantly lower peak SR values and change in SR with no difference in resting measures. A linear regression model showed that the relative wall thickness and extent of CAD were the strongest predictors of change in SR. An increasing extent of CAD caused a steady degradation in the peak SR and change in peak SR. Markers of longitudinal myocardial deformation at peak stress reflect both myocardial and interstitial properties. In conclusion, a major determinant of subendocardial function is the wall thickness, as measured by the relative wall thickness, and not LV hypertrophy.

Limited information exists regarding the significance of dyspnea in patients who are unable to exercise and the contribution of myocardial ischemia to this symptom. To assess this, we evaluated results of dobutamine stress echocardiography (DSE) and long-term outcome of patients with dyspnea referred for DSE. We studied 6,376 consecutive patients who were unable to perform an exercise test and were referred for DSE. Patients were classified according to presenting symptoms and followed for 5.5 +/- 2.8 years. End points were cardiac ischemic events (myocardial infarction or revascularization), hospitalization for heart failure (HF), and death. Dobutamine stress echocardiogram was positive for ischemia in 19% of patients with dyspnea versus 24% (p = 0.002) of those with typical angina and 17% (p = 0.2) of asymptomatic patients. In multivariate analysis, risk of death was increased in dyspneic patients versus asymptomatic patients (hazard ratio [HR] 1.14, p = 0.02) and patients with chest pain (HR 1.20, p <0.001). Hospitalization for HF occurred more often in patients with dyspnea (HR 1.26, p = 0.05 vs asymptomatic; HR 1.24, p = 0.06 vs chest pain), especially in the subset without previous HF (HR 1.45, p = 0.006 vs chest pain). Risk of cardiac ischemic events in patients with dyspnea was similar versus asymptomatic patients (HR 0.92, p = 0.39) and decreased versus patients with chest pain (HR 0.70, p <0.001). In conclusion, in patients referred for DSE, dyspnea was associated with a poor outcome. This increased hazard seems not to be linked to myocardial ischemia, but instead to HF and death.

Limited studies are available demonstrating the safety of contrast agents in patients undergoing stress echocardiography and none in patients with suspected acute coronary syndrome (ACS). Therefore, we sought to assess the safety profile of contrast agents in patients with stable chest pain and in those with suspected ACS (nondiagnostic electrocardiogram and negative initial 12-hour cardiac troponin test results). During a 4-year period, 3,704 patients underwent stress echocardiography (exercise or dobutamine), of whom, 929 (25%) had suspected ACS. Contrast agents (SonoVue 46%, Luminity 54%) were used in 1,150 patients (31%). No patients died with or without contrast administration. No nonfatal acute myocardial infarction occurred in patients administered contrast agents compared with 3 cases of acute myocardial infarction in the noncontrast group (p = 0.24). Two cases of sustained ventricular tachycardia developed, one in each group (p = 0.98). Compared with those who did not receive contrast, patients in both the stable chest pain and the suspected ACS groups had a greater burden of cardiovascular risk factors. The left ventricular function at rest was significantly worse in the patients who received contrast than in those who did not in the suspected ACS group. Also, a greater ischemic burden was present in those receiving contrast than in those not receiving it in both the stable chest pain and the suspected ACS groups. In conclusion, despite the presence of greater risk features compared with patients undergoing unenhanced stress echocardiography, the administration of ultrasound contrast agents (SonoVue and Luminity) in those with stable chest pain and those with suspected ACS was not associated with excess adverse events.

The mechanisms for abnormal stress echocardiograms (SEs) in patients with normal coronary arteries have not been clearly elucidated. We hypothesized that in some patients, this phenomenon may represent a forme fruste of apical ballooning syndrome (ABS). The aim of the study was to evaluate the characteristics of patients with strongly false-positive SEs and determine whether there were similarities to ABS. Thirty-one patients from the Mayo Clinic stress echocardiography database who had normal function at rest, extensive regional wall motion abnormalities in association with an abnormal response of left ventricular end-systolic cavity size at peak stress, and angiographically normal coronary arteries were evaluated. Eighty-four percent were women with a mean age of 61 +/- 12 years, 6% had a positive stress electrocardiogram, and only 26% had a hypertensive response to stress. In 81%, left ventricular ejection fraction decreased with stress and 97% developed new regional wall motion abnormalities in > or =4 segments. Peak wall motion score index was 1.65 +/- 0.39. Midventricular (100%) and apical (87%) segments were most often involved with relative sparing of the basal segments (77%; p = 0.01). There were no deaths during follow-up (2.3 +/- 0.7 years). In conclusion, the major findings of this study were that strongly false-positive SEs occurred predominantly in postmenopausal women, and frequently involved the apical and mid-left ventricular segments, features that were similar to ABS. Data were consistent with the hypothesis that some false-positive SEs may represent a forme fruste of ABS.

Prophylactic coronary revascularization in vascular surgery patients with extensive coronary artery disease was not associated with an improved immediate postoperative outcome. However, the potential long-term benefit was unknown. This study was performed to assess the long-term benefit of prophylactic coronary revascularization in these patients. Of 1,880 patients scheduled for major vascular surgery, 430 had > or =3 risk factors (age >70 years, angina pectoris, myocardial infarction, heart failure, stroke, diabetes mellitus, and renal failure). All underwent cardiac testing using dobutamine echocardiography or nuclear stress imaging. Patients with extensive stress-induced ischemia (> or =5 segments or > or =3 walls) were randomly assigned to additional revascularization. In total, 101 patients showed extensive ischemia and were assigned to revascularization (n = 49) or no revascularization (n = 52). After 2.8 years, the overall survival rate was 64% for patients randomly assigned to no preoperative coronary revascularization versus 61% for patients assigned to preoperative coronary revascularization (hazard ratio [HR] 1.18, 95% confidence interval [CI] 0.63 to 2.19, p = 0.61). Rates for survival free of all-cause death, nonfatal myocardial infarction, and coronary revascularization were similar in both groups at 49% and 42% for patients allocated to medical treatment or coronary revascularization, respectively (HR 1.51, 95% CI 0.89 to 2.57, p = 0.13). Only 2 patients assigned to medical treatment required coronary revascularization during follow-up. Also, in patients who survived the first 30 days after surgery, there was no apparent benefit of revascularization on cardiac events (HR 1.35, 95% CI 0.72 to 2.52, p = 0.36). In conclusion, preoperative coronary revascularization in high-risk patients undergoing major vascular surgery was not associated with improved postoperative or long-term outcome compared with the best medical treatment.