Patients with systemic right ventricles frequently experience progressive heart failure and conduction abnormalities leading to abnormal ventricular activation. Activation delay-induced mechanical ...dyssynchrony can contribute to ventricular failure and is identified by a classic strain pattern of paradoxical opposing wall motion that is an excellent predictor of response to cardiac resynchronization therapy in adults with left bundle branch block. The specific aims of this study were to compare right ventricular (RV) mechanics in an adult systemic right ventricle population versus control subjects, evaluate the feasibility of this RV strain pattern analysis, and determine the frequency of the classic pattern.
Young adults (n = 25) with d-transposition of the great arteries, status post Mustard or Senning palliation (TGA-MS), were ambispectively enrolled and compared with healthy young adults (n = 30) who were prospectively enrolled. All subjects were imaged using novel three-apical view (18-segment) RV longitudinal speckle-tracking strain analysis (EchoPAC) and electrocardiographic data.
Patients with TGA-MS had diminished RV global peak systolic strain compared with control subjects (-12.0 ± 4.0% vs -23.3 ± 2.3%, P < .001). Most patients with TGA-MS had intrinsic or left ventricular paced right bundle branch block. A classic pattern was present in 11 of 25 subjects (44%), but this pattern would have been missed in four of 11 based only on the RV four-chamber (six-segment) model. Only three subjects underwent cardiac resynchronization therapy. Both subjects who had the classic pattern responded to cardiac resynchronization therapy, whereas the one nonresponder did not have the classic pattern.
Systemic right ventricles demonstrated decreased function and increased mechanical dyssynchrony. The classic pattern of activation delay-induced mechanical dyssynchrony was frequently seen in this TGA-MS population and associated with activation delays. This comprehensive RV approach demonstrated incremental value.
Background Although adequate representation of specific subgroups (eg, women and the elderly) in randomized controlled trials (RCTs) has been under intense scrutiny, there are few data on ...representation by race. Methods Using all RCTs cited by the 2007 American Heart Association guidelines for cardiovascular disease prevention in women (although trials were included whether or not there were female participants), we explored the extent to which information on race was reported in the baseline characteristics. Race/ethnicity categories were whites, blacks, Asians, Hispanics, and “others.” Results Overall, 156 trials were analyzed. Demographic data on race/ethnicity were reported in 55 (35%) trials and increased significantly over time (1970s, 12.5%; 1980s, 25%; 1990s, 30.5%; 2000s, 46.2%; P for trend = .011). Among the 55 trials reporting any race/ethnicity information, trial inclusion of whites, blacks, Asians, Hispanics, and “others” was reported in 27%, 13%, 14%, 5%, and 10% of trials, respectively, and increased over time ( P for trend < .05 for all). Trials enrolling subjects only in the United States or globally, including the US, were more likely to report race composition than trials that included no US sites (US only 64% vs global 62% vs non-US 21%, P < .01). Industry- and federal/foundation-funded RCTs reported race with similar frequency (industry 36% vs federal 34% vs both 24%, P = .44). When we isolated our analyses to trials that were funded by the National Institutes of Health, 12 (67%) of 18 RCTs reported race/ethnicity as a baseline characteristic. Conclusion Although reporting the race/ethnic composition of study populations is increasing over time, two thirds of all RCTs supporting a recent American Heart Association () guideline failed to publish any information on race. A necessary first requirement in translating RCT evidence to patients of all races is information regarding racial demographics. Such information should be strongly encouraged in future publications.
Objectives To evaluate the use of surrogate measures in pulmonary hypertension (PH) clinical trials and how it relates to clinical practice. Background Studies of pulmonary arterial hypertension ...(PAH) employ a variety of surrogate measures in addition to clinical events because of a small patient population, participant burden, and costs. The use of these measures in PH drug trials is poorly defined. Methods We searched PubMed/MEDLINE/Embase for randomized or prospective cohort PAH clinical treatment trials from 1985 to 2013. Extracted data included intervention, trial duration, study design, patient characteristics, and primary and secondary outcome measures. To compare with clinical practice, we assessed the use of surrogate measures in a clinical sample of patients on PH medications at Duke University Medical Center between 2003 and 2014. Results Between 1985 and 2013, 126 PAH trials were identified and analyzed. Surrogate measures served as primary endpoints in 119 trials (94.0%). Inclusion of invasive hemodynamics decreased over time (78.6%, 75.0%, 52.2%; P for trend = .02), while functional testing (7.1%, 60.0%, 81.5%; P for trend < .0001) and functional status or quality of life (0%, 47.6%, 62.8%; P for trend < .0001) increased in PAH trials over the same time periods. Echocardiography data were reported as a primary or secondary outcome in 32 trials (25.4%) with increased use from 1985-1994 to 1995-2004 (7.1% vs 35.0%, P = .04), but the trend did not continue to 2005-2013 (25.0%). In comparison, among 450 patients on PAH therapies at our institution between 2003 and 2013, clinical assessments regularly incorporated serial echocardiography and 6-minute walk distance tests (92% and 95% of patients, respectively) and repeat measurement of invasive hemodynamics (46% of patients). Conclusions The majority of PAH trials have utilized surrogate measures as primary endpoints. The use of these surrogate endpoints has evolved significantly over time with increasing use of patient-centered endpoints and decreasing or stable use of imaging and invasive measures. In contrast, imaging and invasive measures are commonly used in contemporary clinical practice. Further research is needed to validate and standardize currently used measures.
Background We compared 30-day and 1-year survival among high-risk mitral regurgitation (MR) patients treated with the MitraClip (Abbott Vascular, Abbott Park, IL) with matched non-surgically treated ...patients from the Duke Echocardiography Laboratory Database (DELD). Methods and Results High-risk patients with 3+/4+ MR managed non-surgically between years 2000 and 2010 in the longitudinal DELD were matched to high-risk MitraClip patients. Patient matching was performed using the method of nearest available Mahalanobis distance metric within calipers defined by the propensity score. Kaplan-Meier estimates and stratified Cox proportional hazards models were used to compare survival at 30 days and 1 year. Among 953 high-risk DELD patients available for matching, 30-day and 1-year mortality were 6.5% and 26.2%. Close matches were obtained for 239 of the 351 MitraClip patients. The 30-day mortality in MitraClip patients was lower (4.2%) when compared with matched DELD patients (7.2%). The 1-year relative risk of mortality of the MitraClip compared with non-surgical treatment was 0.64 (95% CI 0.45-0.91; log-rank P = .013). These results in favor of the MitraClip remained significant upon further adjustment for baseline differences between groups ( P = .043). Conclusions This matched comparison of severe MR patients at high surgical risk supports the safety of the MitraClip relative to medical therapy at 30 days and a survival benefit at 1 year.
In patients with suspected native valve infective endocarditis, current guidelines recommend initial transthoracic echocardiography (TTE) followed by transesophageal echocardiography (TEE) if ...clinical suspicion remains. The guidelines do not account for the quality of initial TTE or other findings that may alter the study's diagnostic characteristics. This may lead to unnecessary TEE when initial TTE was sufficient to rule out vegetation.
The objective of this study was to determine if the use of a strict definition of negative results on TTE would improve the performance characteristics of TTE sufficiently to exclude vegetation. A retrospective analysis of patients at a single institution with suspected native valve endocarditis who underwent TTE followed by TEE within 7 days between January 1, 2007, and February 28, 2014, was performed. Negative results on TTE for vegetation were defined by either the standard approach (no evidence of vegetation seen on TTE) or by applying a set of strict negative criteria incorporating other findings on TTE. Using TEE as the gold standard for the presence of vegetation, the diagnostic performance of the two transthoracic approaches was compared.
In total, 790 pairs of TTE and TEE were identified. With the standard approach, 661 of the transthoracic studies had negative findings (no vegetation seen), compared with 104 studies with negative findings using the strict negative approach (meeting all strict negative criteria). The sensitivity and negative predictive value of TTE for detecting vegetation were substantially improved using the strict negative approach (sensitivity, 98% 95% CI, 95%-99% vs 43% 95% CI, 36%-51%; negative predictive value, 97% 95% CI, 92%-99% vs 87% 95% CI, 84%-89%).
The ability of TTE to exclude vegetation in patients is excellent when strict criteria for negative results are applied. In patients at low to intermediate risk with strict negative results on TTE, follow-up TEE may be unnecessary.
Objective The authors hypothesized that average precardiopulmonary bypass (pre-CPB) transesophageal echocardiographic (TEE) mean gradient (PGm ) and aortic valve area (AVA) values would be ...significantly different from preoperative transthoracic (TTE) values in the same patients and that these changes would affect pre-CPB TEE grading of aortic stenosis (AS). Design Retrospective, observational design. Setting Single university hospital. Participants The study comprised 92 patients who underwent aortic valve replacement with or without coronary artery bypass grafting between 2000 and 2012 at Duke University Hospital and who had PGm and AVA values recorded in both pre-CPB TEE and preoperative TTE reporting databases. Interventions None. Measurements and Main Results PGm with pre-CPB TEE was lower by 6.6 mmHg (95% confidence interval, –4.0 to –9.3 mmHg; p<0.001), whereas AVA was higher by 0.10 cm2 (95% confidence interval, 0.04 to 0.15 cm2 ; p<0.001), compared with preoperative TTE values. When using PGm , pre-CPB TEE generated an AS severity 1 grade lower 39.1% of the time and revealed no difference 55.4% of the time compared to preoperative TTE. When using AVA by continuity, pre-CPB TEE generated an AS severity 1 grade lower 14.1% of the time and revealed no difference 81.5% of the time compared to preoperative TTE. When using either PGm or AVA, preoperative TTE exhibited moderate or severe AS for all study patients, whereas, pre-CPB TEE demonstrated mild AS in 5.4% (n = 92) of patients. Conclusions The authors confirmed their hypothesis that pre-CPB TEE generates different PGm and AVA values compared with preoperative TTE. These differences often underestimate AS severity. Hemodynamic standardizations or adjustments of pre-CPB TEE PGm and AVA values may be necessary in anesthetized patients before assigning an AS grade using these parameters.
We aimed to characterize the hemodynamic progression of aortic stenosis (AS) in a contemporary unselected cohort of patients with preserved left ventricular ejection fraction. Current guidelines ...recommend echocardiographic surveillance of hemodynamic progression. However, limited data exist on the expected rate of progression and whether clinical variables are associated with accelerated progression in contemporarily managed patients with AS. We conducted a retrospective analysis of patients presenting with AS and explored the trajectory of AS mean gradient over time using generalized estimating equations and fit a longitudinal linear regression model with adjustment for baseline clinical variables. A total of 1,558 patients (median age 72; interquartile range 65 to 79) having mild (n = 982), moderate (n = 363), or severe AS (n = 213) were included. In patients with mild AS at baseline (n = 983), 303 (31%) had progressed to moderate/severe AS/AVR within 5 years of the index echo. In patients with moderate AS, 159 of 363 (44%) had progressed to severe AS/AVR within 2 years of the index echo. The annual change in mean gradient was dependent on baseline AS severity. Average annual increases in mean gradient were 6.8% (95% confidence interval 6.0 to 7.6) and 7.1% (95% confidence interval 4.8 to 9.3) in patients with mild and moderate AS, respectively. In the subset of patients with mild AS at baseline, age (p = 0.0310) and gender (p = 0.0270) had significant interaction with change in mean gradient over time. In patients with moderate AS, age (p <0.0001), gender (p = 0.0346), renal dysfunction (p = 0.0036), and hyperlipidemia (p = 0.0010) demonstrated significant interaction with change in mean gradient over time. In conclusion, although average disease progression was slower than previously reported, a significant proportion of patients with mild and moderate AS progressed to higher grades within the currently recommended time windows for echocardiographic follow-up.
Objectives The aim of this study was to investigate the association between resting myocardial function as assessed by tissue Doppler myocardial velocities and the propensity to develop mental ...stress–induced ischemia (MSIMI). Background Tissue Doppler myocardial velocities detect preclinical cardiac dysfunction and clinical outcomes in a range of conditions. However, little is known about the interrelationship between myocardial velocities and the propensity to develop MSIMI compared with exercise stress–induced myocardial ischemia. Methods Resting annular myocardial tissue Doppler velocities were obtained in 225 patients with known coronary heart disease who were subjected to both conventional exercise stress testing as well as a battery of 3 mental stress tests. Diastolic early (e′) and late (a′) as well as systolic (s′) velocities were obtained, and the eas index, an integrated measure of myocardial velocities, was calculated as e′/(a′ × s′). MSIMI was defined as: 1) the development or worsening of regional wall motion abnormality; 2) a reduction in left ventricular ejection fraction ≥ 8%; and/or 3) ischemic ST-segment changes during 1 or more of the 3 mental stress tests. Results A total of 98 of 225 patients (43.7%) exhibited MSIMI. Patients developing MSIMI had significantly lower s′ (7.0 ± 1.7 vs. 7.5 ± 1.2, p = 0.016) and a′ (8.9 ± 1.8 vs. 10.0 ± 1.9, p < 0.001) at baseline, whereas e′ did not differ (6.5 ± 1.7 vs. 6.5 ± 1.8, p = 0.85). Furthermore, the eas index was significantly higher (0.11 ± 0.04 vs. 0.09 ± 0.03, p < 0.0001). The eas index remained significantly associated with the propensity to develop MSIMI (odds ratio per 0.05-U increase: 1.85; 95% confidence interval: 1.21 to 2.82; p = 0.004) after adjustment for resting left ventricular ejection fraction, resting wall motion index score, sex, and social circumstances of living. There was no association between resting eas index and exercise stress–induced myocardial ischemia. Conclusions MSIMI but not exercise stress–induced myocardial ischemia is independently associated with resting abnormalities in myocardial systolic and late diastolic velocities as well as the integrated measure of the eas index in patients with known coronary artery disease. (Responses of Myocardial Ischemia to Escitalopram Treatment REMIT; NCT00574847 )
Objectives The aim of this study was to evaluate the impact of renal function by estimated glomerular filtration rate (eGFR) on risk stratification of diabetic and nondiabetic patients undergoing ...myocardial perfusion imaging (MPI) by single-photon emission computed tomography for suspected ischemia. Background Coronary artery disease is the leading cause of death among diabetic persons; however, diabetic persons are a very heterogeneous group in terms of cardiovascular risk, necessitating further risk stratification. Methods Patients (n = 1,747, age 65 ± 10 years, 37% diabetic) undergoing MPI were followed for cardiac death (CD) for a mean of 2.15 ± 0.8 years. Chronic kidney disease (CKD) was defined by an eGFR <60 ml/min. Results In the presence of a normal scan, annual CD rate was 0.9% for those with no diabetes mellitus (DM) and no CKD, 0.5% in the DM alone group, 2.35% in CKD alone, and 2.9% in those with both DM and CKD (p < 0.001). Patients with DM+CKD had a 2.7-fold risk of CD compared with no DM no CKD (p = 0.001) after controlling for age, ejection fraction, history of coronary artery disease, and other risk factors. The risk of CD increased as a function of the presence and severity of perfusion defects, regardless of CKD or DM status. Presence of CKD conferred a several-fold higher risk of CD for the various strata of perfusion defects. Log-rank test for difference in probability of CD was nonsignificant for comparison between patients with no DM no CKD and those with DM alone (p = 0.73) but was significant for comparison between patients with no DM no CKD and patients with CKD alone (p < 0.001) or DM+CKD (p < 0.001). Conclusions MPI and eGFR provide valuable risk stratification for diabetic and nondiabetic patients. Diabetic patients without CKD seem to have similar short-term cardiac outcomes compared with nondiabetic patients. Underlying CKD seems to identify a high-risk subgroup of diabetic patients.
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