Design and methods of the Echo WISELY (Will Inappropriate Scenarios for Echocardiography Lessen SignificantlY) study: An investigator-blinded randomized controlled trial of education and feedback intervention to reduce inappropriate echocardiograms.

BACKGROUND: Appropriate use criteria (AUC) for transthoracic echocardiography (TTE) were developed to address concerns regarding inappropriate use of TTE. A previous pilot study suggests that an educational and feedback intervention can reduce inappropriate TTEs ordered by physicians in training. It is unknown if this type of intervention will be effective when targeted at attending level physicians in a variety of clinical settings. AIMS: The aim of this international, multicenter study is to evaluate the hypothesis that an AUC-based educational and feedback intervention will reduce the proportion of inappropriate echocardiograms ordered by attending physicians in the ambulatory environment. METHODS: In an ongoing multicentered, investigator-blinded, randomized controlled trial across Canada and the United States, cardiologists and primary care physicians practicing in the ambulatory setting will be enrolled. The intervention arm will receive (1) a lecture outlining the AUC and most recent available evidence highlighting appropriate use of TTE, (2) access to the American Society of Echocardiography mobile phone app, and (3) individualized feedback reports e-mailed monthly summarizing TTE ordering behavior including information on inappropriate TTEs and brief explanations of the inappropriate designation. The control group will receive no education on TTE appropriate use and order TTEs as usual practice. CONCLUSIONS: The Echo WISELY (Will Inappropriate Scenarios for Echocardiography Lessen Significantly in an education RCT) study is the first multicenter randomized trial of an AUC-based educational intervention. The study will examine whether an education and feedback intervention will reduce the rate of outpatient inappropriate TTEs ordered by attending level cardiologists and primary care physicians (www.clinicaltrials.gov identifier NCT02038101).

Mitral chordal-leaflet-myocardial interactions in mitral valve prolapse.

BACKGROUND: The submitral apparatus maintains annular-papillary continuity and myocardial geometry. In mitral valve prolapse (MVP), elongated chords and redundant leaflets can interact at the region of myocardial attachment, leading to apparent discordant motion of the basal inferolateral wall. The aim of this study was to test the hypothesis that basal inferolateral wall inward motion would occur later in MVP and that this delay is associated with MVP severity. METHODS: Thirty consecutive patients with MVP and matched controls underwent stress echocardiography. Time to peak transverse displacement (TPD) of the inferolateral wall compared with the anteroseptal wall was measured using speckle-tracking echocardiography. The time difference was analyzed as raw data, normalized to the RR interval, and as a percentage of the time to maximal displacement of the anteroseptal segment(s). RESULTS: Compared with controls, TPD was delayed in patients with MVP both at rest and at peak stress, when evaluating basal segments or basal-mid segments as a unit, both in real time and, more importantly, when correcting for anteroseptal TPD. In patients compared with controls, observed delay at rest and at peak stress was 50 ± 90 versus -30 ± 90 msec (P = .006) and 70 ± 80 versus -30 ± 60 msec (P < .0001), respectively; relative to TPD of the anteroseptal segment, the observed delay at rest and at peak stress was 117 ± 24% versus 97 ± 22% (P = .007) and 144 ± 68% versus 95 ± 21% (P = .003), respectively. Similar significant findings were observed in basal-mid segments. TPD results were not statistically significant when stratified by prolapse severity. Intraclass correlation coefficients were 0.88 and 0.93, and two-tailed t tests indicated good interobserver and intraobserver variability. CONCLUSIONS: Inferolateral wall TPD is delayed in MVP. TPD is a novel method to characterize chordal-leaflet-myocardial interactions in patients with MVP. Prolapse severity does not predict TPD, likely because of the timing of prolapse and dynamic loading conditions. Implications of this observation include attribution of a perceived wall motion abnormality in MVP during stress echocardiography to a physiologic state and new mechanistic insights into mitral valve physiology.

Heart rate is associated with increased risk of major cardiovascular events, cardiovascular and all-cause death in patients with stable chronic cardiovascular disease: an analysis of ONTARGET/TRANSCEND.

AIMS: Heart rate was proposed as an emergent cardiovascular (CV) risk factor. Previous studies have shown associations between increased heart rate and CV risk in various populations. We aimed to evaluate the prognostic relevance of heart rate in a large contemporaneous medically optimized cohort of patients with stable chronic CV disease. METHODS AND RESULTS: In a post hoc analysis of the ONTARGET/TRANSCEND trials, we evaluated associations between baseline and average heart rate in trial with CV risk in 31, 531 patients followed for a median of 5 years. The primary outcome, major vascular events (MVE), was a composite of CV death, myocardial infarction (MI), stroke, and congestive heart failure (CHF). Pre-specified secondary outcomes included all-cause death and the individual components of the primary outcome. Associations between heart rate and outcomes were computed with heart rate as a continuous variable, baseline heart rate >70 vs ≤ 70 bpm, and across heart rate quintiles, adjusting for other markers of risk, beta-blocker and non-dihydropyridine calcium channel blocker use. For each 10 bpm increase in baseline and average heart rate, we observed a significant increase in risk of MVE, CV death, CHF and all-cause death. There was a continuous relationship between MVE and baseline and, more importantly, average in-trial heart rate, with no observed threshold. MVE, CV death, stroke, CHF, and all-cause death increased across heart rate quintiles. There was no association between MI and HR. Results were consistent in clinically relevant subgroups. There were modest but significant improvements in C-statistic and in statistical measures of model calibration for models that included heart rate for MVE, CV death, CHF and all-cause death. CONCLUSIONS: This large study examined and quantitated associations between heart rate and CV events in a contemporary medically optimized population with stable CV disease. Resting and, in particular, in-trial average heart rate are independently associated with significant increases in CV events and all-cause death.

Right ventricular involvement in patients with coronary artery disease.

PURPOSE OF REVIEW: RV involvement in coronary artery disease (CAD) includes isolated infarction and involvement in left ventricular infarction. Right ventricular involvement with left ventricular infarction has unique clinical signs and symptoms, requires different management, and has worse prognosis than left ventricular infarcts without right ventricular involvement. Although the right ventricle (RV) is geometrically complex, advances in echocardiography, nuclear imaging, computed tomography, and magnetic resonance imaging technologies have helped to optimally visualize its structure and function and to better elucidate its role in CAD. RECENT FINDINGS: Newer noninvasive imaging modalities to visualize the RV are highlighted and their emerging clinical utilities are emphasized, including three-dimensional echocardiography, tissue Doppler velocity and strain imaging, computed tomography, and MRI. SUMMARY: The RV is often involved in CAD. Available imaging modalities demonstrate different aspects of right ventricular involvement, yielding new insights into pathophysiology, clinical care, and management. As imaging technologies widen in their scope, cardiologists will increasingly have the imaging tools to integrate information on right ventricular morphology, hemodynamics, and function, enabling appropriate care for patients with right ventricular involvement in CAD.

Left ventricular dysfunction and mortality in adult patients with Eisenmenger syndrome.

OBJECTIVES: To identify risk factors associated with mortality in adult patients with Eisenmenger syndrome and to assess the effect of left ventricular dysfunction on mortality in these patients. METHODS AND RESULTS: One hundred twenty-two adult patients with Eisenmenger syndrome were retrospectively evaluated for signs and symptoms of heart failure, and underwent electrocardiography and laboratory investigations. Available echocardiograms were analyzed and left ventricular function was assessed both qualitatively and quantitatively. There were 47 deaths at 37.8 +/- 12.0 years of age. On univariate analysis clinical signs and symptoms of heart failure, right ventricular hypertrophy on electrocardiography, wide QRS (QRS duration >130 milliseconds), and left ventricular dysfunction (left ventricular ejection fraction [LVEF] <50%) on echocardiography were associated with mortality. On multivariate analysis, signs and symptoms of heart failure, right ventricular hypertrophy on electrocardiography, and LVEF <50% remained strong predictors of death. CONCLUSIONS: Signs and symptoms of heart failure predict mortality in patients with Eisenmenger syndrome. Furthermore, patients with left ventricular dysfunction (LVEF <50%) have higher mortality. A combination of signs and symptoms of heart failure, right ventricular hypertrophy on electrocardiography, and left ventricular dysfunction on echocardiography provides the most powerful predictor of death in patients with Eisenmenger syndrome.

Eisenmenger syndrome and atrial septal defect: nature or nurture?

BACKGROUND: It has long been debated whether patients with atrial septal defect (ASD) Eisenmenger syndrome have idiopathic pulmonary arterial hypertension with an incidental ASD or severe pulmonary hypertension on the basis of their ASD shunt magnitude alone. HYPOTHESIS: It was hypothesized that if ASD Eisenmenger patients had idiopathic pulmonary arterial hypertension with an incidental ASD, a mutation in the bone morphogenetic protein receptor-2 (BMPR2) would be found in some of these patients. PATIENTS AND METHODS: All adult patients with ASD Eisenmenger syndrome were identified from the databases of two adult congenital cardiac units, and were matched to a control group with similar types of ASDs and no pulmonary hypertension. Gene coding for BMPR2 was examined for mutation using denaturing high-performance liquid chromatography of the entire coding sequence. RESULTS: Eighteen adult patients with ASD Eisenmenger syndrome and 18 control patients were identified. ASD Eisenmenger patients had significantly larger ASDs than the control patients (3.7+/-1.2 cm versus 1.9+/-0.7 cm, P<0.01). A mutation in BMPR2 was not detected in either group. CONCLUSION: ASD Eisenmenger syndrome may occur without BMPR2 mutation. Whether shunt magnitude alone or in combination with yet another genetic mutation is responsible for the development of pulmonary hypertension in these patients remains to be determined.