Comprehensive Echocardiographic Assessment of Normal Transcatheter Valve Function.

OBJECTIVES: This study aims to establish parameters for identifying normal function for each of the 3 iterations of balloon-expandable valves and 2 iterations of self-expanding valves. BACKGROUND: Expected transthoracic echocardiographic Doppler-derived hemodynamic data for transcatheter aortic valves inform pre-implant decision-making and post-implanted monitoring of longitudinal valve function. METHODS: We collected the echocardiography core Lab measured mean gradients and effective orifice area (EOA) from discharge or 30-day echocardiograms from randomized trials; the PARTNER (Placement of Aortic Transcatheter Valves) trials for the balloon-expandable valves and the Medtronic CoreValve US Pivotal trial and Medtronic CoreValve Evolut R United States IDE Clinical Study for the self-expanding valves. RESULTS: For all SAPIEN (Edwards Lifesciences, Irvine, California) valve sizes, mean EOA is 1.70 ± 0.49 cm2 with a mean gradient of 9.36 ± 4.13 mm Hg. For all SAPIEN XT valve sizes, mean EOA is 1.67 ± 0.46 cm2 with a mean gradient of 9.52 ± 3.64 mm Hg. For all SAPIEN 3 valve sizes, the mean EOA is 1.66 ± 0.38 cm2 with a mean gradient of 11.18 ± 4.35 mm Hg. For all CoreValve valve sizes, the mean EOA is 1.88 ± 0.56 cm2 with a mean gradient of 8.85 ± 4.14 mm Hg. For all Evolut R valve sizes, the mean EOA is 2.01 ± 0.65 cm2 with a mean gradient of 7.52 ± 3.19 mm Hg. The SAPIEN 3 post-implant EOA was progressively larger for each quintile of baseline annular area by computed tomography (p < 0.001). Similarly, for the Evolut R valve, post-implantation EOA was significantly larger for each quintile of baseline annular perimeter (p < 0.001). CONCLUSIONS: Tables of expected mean transcatheter aortic valve hemodynamics by valve type and size are essential in evaluating the function of these transcatheter prosthetic valves. Tables of expected EOA by the native annular anatomy may be useful for pre-implantation decision making. Criteria for defining structural valve dysfunction are proposed.

Cardiovascular Outcomes Assessment of the MitraClip in Patients with Heart Failure and Secondary Mitral Regurgitation: Design and rationale of the COAPT trial.

BACKGROUND: Patients with heart failure (HF) and symptomatic secondary mitral regurgitation (SMR) have a poor prognosis, with morbidity and mortality directly correlated with MR severity. Correction of isolated SMR with surgery is not well established in this population, and medical management remains the preferred approach in most patients. The Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) trial was designed to determine whether transcatheter mitral valve (MV) repair with the MitraClip device is safe and effective in patients with symptomatic HF and clinically significant SMR. STUDY DESIGN: The COAPT trial is a prospective, randomized, parallel-controlled, open-label multicenter study of the MitraClip device for the treatment of moderate-to-severe (3+) or severe (4+) SMR (as verified by an independent echocardiographic core laboratory) in patients with New York Heart Association class II-IVa HF despite treatment with maximally tolerated guideline-directed medical therapy (GDMT) who have been determined by the site's local heart team as not appropriate for MV surgery. A total of 614 eligible subjects were randomized in a 1:1 ratio to MV repair with the MitraClip plus GDMT versus GDMT alone. The primary effectiveness end point is recurrent HF hospitalizations through 24 months, analyzed when the last subject completes 12-month follow-up, powered to demonstrate superiority of MitraClip therapy. The primary safety end point is a composite of device-related complications at 12 months compared to a performance goal. Follow-up is ongoing, and the principal results are expected in late 2018. CONCLUSIONS: HF patients with clinically significant SMR who continue to be symptomatic despite optimal GDMT have limited treatment options and a poor prognosis. The randomized COAPT trial was designed to determine the safety and effectiveness of transcatheter MV repair with the MitraClip in symptomatic HF patients with moderate-to-severe or severe SMR.

Assessment of paravalvular regurgitation following TAVR: a proposal of unifying grading scheme.

Paravalvular regurgitation (PVR) is a frequent complication of transcatheter aortic valve replacement that has been shown to be associated with increased mortality. The objective of this article is to review the most up-to-date information about the assessment and management of PVR and to propose a new more comprehensive and unifying scheme for grading PVR severity. A multimodality, multiparametric, integrative approach including Doppler echocardiography, cineangiography, hemodynamic assessment, and/or cardiac magnetic resonance is essential to accurately assess the severity of PVR and the underlying etiology. Corrective procedures such as balloon post-dilation, valve-in-valve, or leak closure may be considered, depending on the severity, location, and etiology of PVR.

Assessment of paravalvular aortic regurgitation after transcatheter aortic valve replacement: intra-core laboratory variability.

BACKGROUND: There is significant disparity in the reported incidence of moderate and severe paravalvular aortic regurgitation (PAR) between the Placement of Aortic Transcatheter Valves (PARTNER) I and PARTNER II trials, which may be related to the echocardiographic methodologies used by separate core laboratories. To further explore the variability in echocardiographic interpretation of PAR, agreement between the grading of PAR by the core laboratory of PARTNER IIB was compared with that by a consortium of echocardiography core laboratory directors. METHODS: The PARTNER IIB core laboratory reevaluated patients using primarily the circumferential extent of the regurgitant jet for PAR. A consortium of echocardiography core laboratory directors was formed to evaluate the echocardiographic images and to grade PAR and central and total aortic regurgitation in a randomly chosen subset of the randomized patients in the PARTNER IIB trial using a multiwindow, multiparametric approach. Both a four-class scale (none or trace, mild, moderate, and severe) and a seven-class (none, trace, mild, mild to moderate, moderate, moderate to severe, and severe) scale were used. Levels of grading agreement between the consortium and original core laboratory in both scales were determined using weighted κ statistics. RESULTS: Only 87 patients assessed for PAR by the consortium could be paired with readings by the PARTNER IIB core laboratory. Using the four-class grading scheme the weighted κ statistic for PAR was 0.481 (95% confidence limits, 0.367, 0.595). Using the seven-class scale, the weighted κ statistic for PAR was 0.517 (95% confidence limits, 0.431, 0.607). For either grading scheme, 15.9% of patients graded by the PARTNER IIB core laboratory as having moderate PAR would have been graded as having mild PAR using the multiparametric approach. Similar results were seen for central and total aortic regurgitation assessments. CONCLUSIONS: Using primarily the circumferential extent criteria, the PARTNER IIB core laboratory overestimated the severity of PAR compared to the consortium using a multi-parametric approach. Although a more granular classification scheme for PAR may slightly improve concordance between core laboratories, differences in the incidence of moderate or severe PAR are likely related to differences in grading methodology. A multiparametric approach is advocated, and other echocardiographic methods for assessing PAR deserve further study.

Cardiovascular imaging payment and reimbursement systems: understanding the past and present in order to guide the future.

Uncertainty regarding the future of cardiovascular (CV) services and reimbursement systems in this era of rapid change in health care delivery may lead to further confusion among imagers. This article provides a brief history of national payment and reimbursement systems, and discusses potential changes that will impact CV imaging in the coming years. Data over the last decade are presented on payment and utilization of services to demonstrate the impact of reimbursement reforms and education on imaging use.

Echocardiographic assessment of cardiac valvular regurgitation with lorcaserin from analysis of 3 phase 3 clinical trials.

BACKGROUND: Lorcaserin is a selective 5-HT2C agonist evaluated for weight management in clinical trials. Echocardiographic monitoring was conducted to test the hypothesis that selective 5-HT2C agonism would avoid valvular heart disease. METHODS AND RESULTS: Echocardiographic and weight change data from 5249 obese and overweight patients in 3 phase 3 trials were integrated. Treatment duration with 10 mg lorcaserin twice daily or placebo was 52 weeks. The proportions of patients who developed Food and Drug Administration-defined valvulopathy (≥ mild aortic or ≥ moderate mitral regurgitation) and changes in regurgitant grade at each heart valve were evaluated. Possible associations between weight or body mass index change and valvulopathy were explored. New valvulopathy was present in 2.04% of placebo and 2.37% of lorcaserin recipients at 52 weeks (risk difference, 0.33%; 95% confidence interval, -0.46 to 1.13; risk ratio, 1.16 [all patients with sufficient echocardiographic data, last-observation-carried-forward imputation] or 1.03 [patients who completed 52 weeks]). Changes in weight and body mass index were negatively associated with presence of valvulopathy at week 52 (P=0.02 and P=0.04, respectively); a 5% decrease in weight was associated with an odds ratio of 1.15 for Food and Drug Administration-defined valvulopathy. Most changes in regurgitation were ±1 grade in both treatment groups at all heart valves. CONCLUSIONS: In 3 prospective placebo-controlled trials with integrated data for 5249 patients, the rate of echocardiographic valvulopathy was similar with lorcaserin and placebo. Point estimates for risk ratios ranged from 1.03 to 1.16 and may be at least partially influenced by greater weight loss in the lorcaserin group than in the placebo group. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00395135, NCT00603291, NCT00603902.

Peri-stent reference segment plaque burden is associated with disease progression in saphenous vein grafts (a serial intravascular ultrasound assessment).

We are aware of no studies of peri-stent disease progression or luminal compromise in saphenous vein graft (SVG) lesions. We used serial intravascular ultrasound (IVUS) to assess disease progression in peri-stent saphenous vein bypass graft reference segments. We studied 37 peri-stent SVG reference segments in 21 patients; 16 were proximal and 21 were distal to the stent. The same anatomic image slice was analyzed after the intervention and at follow-up; this site was 3.68 +/- 2.22 mm from the stent edge. Graft age was 10.1 +/- 5.4 years, and mean follow-up duration was 13 months (range 3 to 61). Overall, change in SVG area, change in lumen area, and change in plaque burden correlated with postintervention plaque burden (r = 0.448, p = 0.005; r = -0.584, p <0.001; and r = 0.507, p = 0.001, respectively). For the proximal edge, change in lumen area correlated with change in plaque area (r = -0.951, p <0.001), but not with change in SVG area (r = -0.337, p = 0.201). For the distal edge, change in lumen area correlated more strongly with change in plaque area (r = -0.982, p <0.001) than with change in SVG area (r = -0.624, p = 0.003). When peri-stent reference segments were divided into 2 groups according to postintervention plaque burden (>50% [n = 20] vs <50% [n = 17]), there was a greater decrease in lumen area (-1.12 +/- 0.81 vs -0.33 +/- 0.26 mm(2), p <0.001) and greater increases in SVG area (0.26 +/- 0.29 vs 0.09 +/- 0.09 mm(2), p = 0.027), plaque area (1.37 +/- 0.96 vs 0.42 +/- 0.30 mm(2), p <0.001), and plaque burden (8.2 +/- 5.6% vs. 2.8 +/- 1.6%, p <0.001) in segments with a plaque burden >50%. In conclusion, peri-stent reference segment SVG disease progression and lumen loss were more significant in segments with a greater postintervention plaque burden after implantation of a bare metal stent or drug-eluting stent.

Intravascular ultrasound assessment of the spatial distribution of ruptured coronary plaques in the left anterior descending coronary artery.

BACKGROUND: Plaque rupture is a substrate for thrombosis, occlusion, and myocardial infarction. The left anterior descending coronary artery (LAD) subtends the largest amount of myocardium; therefore, the location of LAD plaque rupture is of particular importance in detecting vulnerable plaques. The aim of our study was to assess the location of ruptured atherosclerotic plaques in the LAD. METHODS: Using intravascular ultrasound, we detected 160 ruptured LAD plaques. Of these, accurate intravascular ultrasound distance measurements (with consistent automatic transducer pullback [0.5 mm/s] to the LAD ostium) could be determined in 112 ruptured plaques. RESULTS: There were 104 patients (91 men, age 63.8 +/- 11.7 years). The total length of the LAD that was imaged measured 48.8 +/- 24.8 mm. The distance from the LAD origin to the maximal plaque cavity was 16.2 +/- 10.3 mm; the maximal plaque cavity was localized to the first 20 mm of the LAD in 71% and the first 30 mm in 88%. Only 2 ruptured plaques were found beyond 40 mm from the LAD ostium. CONCLUSIONS: The majority of LAD ruptured plaques are located within the proximal 30 mm of the artery. This area of the LAD should be targeted for vulnerable (rupture-prone) plaque detection and prevention.

Intravascular ultrasound assessment of ruptured atherosclerotic plaques in left main coronary arteries.

Atherosclerotic plaque rupture is the main cause of acute coronary syndromes. There is no systematic description of ruptured plaques located in the left main coronary artery (LMCA). The aim of our study was to describe ruptured plaques in the LMCA with intravascular ultrasound. We identified 17 LMCA plaque ruptures in 16 patients. Two patients had a recent myocardial infarction, 13 had unstable angina, and 1 had stable angina. Two left main ruptures were clinically considered to be incidental findings and were left untreated; the remaining 14 were culprit lesions that were treated with emergency coronary artery bypass grafting (n = 3) or LMCA stenting (n = 11). One patient died in the hospital after left main stenting for unstable angina; all other patients who underwent stenting or surgical bypass did well. Almost all ruptured plaques that were identified by intravascular ultrasound had an angiographic complex appearance that was defined by the presence of ulceration (81%), intimal flap (38%), aneurysm (12%), or thrombus (6%). All ruptures were located in the distal half of the LMCA; 6 ruptures involved bifurcation and 11 were confined to the LMCA proper. The angle between the maximum plaque cavity and the left anterior descending/left circumflex artery flow divider was 162.3 degrees +/- 15.6 degrees in bifurcation versus 71.3 degrees +/- 41.6 degrees in nonbifurcation lesions (p <0.0001). The LMCA minimum lumen area measured 6.0 +/- 3.3 mm2 in nonbifurcation lesions and 7.4 +/- 4.7 mm2 in bifurcation lesions (p = 0.5). LMCA plaque ruptures mostly present as unstable angina, are located in the distal portion and/or bifurcation of the LMCA, often do not compromise the lumen, and have an angiographic complex appearance. When ruptured plaques involve the bifurcation, they occur opposite the distal flow divider.

Intravascular ultrasound assessment of neointima distribution and the length of stent that was free of intravascular ultrasound-detectable intimal hyperplasia in paclitaxel-eluting stents.

Using data from the ASian Paclitaxel-Eluting Stent Clinical Trial, a 3-center, randomized, placebo-controlled trial of nonpolymeric paclitaxel-coated stents with a single center, 81-patient intravascular ultrasound (IVUS) substudy, the length of a stent that was free of IVUS-detectable intimal hyperplasia measured 3.2 +/- 4.8 mm in placebo stents, 6.1 +/- 5.6 mm in low-dose stents, and 8.7 +/- 6.1 mm in high-dose stents (p = 0.0029). IVUS percent neointima volume obstruction correlated with the length of this IVUS neointima-free segment (r = 0.785, p <0.0001); angiographic late lumen loss and follow-up diameter stenosis also correlated with the IVUS neointima-free length of the stents (r = 0.670, p <0.0001 and r = 0.679, p <0.0001, respectively.

The importance of gender on coronary artery size: in-vivo assessment by intravascular ultrasound.

BACKGROUND: It remains controversial whether women have smaller coronary arteries than men because of a gender-specific trait, or whether the observed differences are primarily due to a difference in body size. Intravascular ultrasound (IVUS), with its ability to provide unique coronary images that allow precise measurement of arterial size in vivo, is ideally suited to address this issue. HYPOTHESIS: Female gender, independent of body size, is associated with smaller coronary artery size as measured by intracoronary ultrasound. METHODS: Intravascular ultrasound images of normal left main arteries were identified retrospectively from a single center database. Associations between demographic and clinical characteristics (including body size) and left main coronary dimensions were assessed with univariant and multivariate regression analyses. RESULTS: We identified 257 completely normal left main arteries. Mean left main arterial areas were smaller in women than in men (17.2 vs. 20.6 mm2, p < 0.001), as were mean luminal areas (14.0 vs. 16.7 mm2, p < 0.001). By multiple regression analysis, the independent predictors of left main lumen were body surface area (p < 0.001) and gender (p = 0. 003). CONCLUSIONS: Body surface area and gender are both independent predictors of coronary artery size, although body size has a greater influence than gender.

Testing the test: the reliability of echocardiography in the sequential assessment of valvular regurgitation.

BACKGROUND AND OBJECTIVE: Substantial variability in serial echocardiographic qualitative assessment of valvular regurgitation may exist. Reader variability is generally well understood, but acquisition variability (portions of variability caused by equipment, sonographers, physiologic changes) has been less frequently assessed, particularly in combination with reader variability. We attempted to determine the relative contributions of acquisition and reader variability as components of total test-retest variability for aortic (AR) and mitral (MR) regurgitation. METHODS: Outpatient echocardiographic study was done at 2 clinical sites. Twenty-three predominantly obese middle-aged females had 3 echocardiograms, 2 performed 14 +/- 3 days apart and the third performed within 1 to 2 hours of the second. Triplets of echocardiograms were evaluated for change in grade of AR and MR. Medical history, anthropometrics, and blood pressures were obtained. RESULTS: Average intrareader variability (percentage of reads for which there is within-reader disagreement) was 5.6% for AR and 16.7% for MR. The average total test-retest variability (percentage of reads for which there is disagreement between visits) was 29.0% for AR and 24.6% for MR. The acquisition variability for AR was 23.4% +/- 7.7%; for MR, it was 7.9% +/- 10.2%. A significant predictor of change for AR/MR was the initial grade. Change in diastolic blood pressure was positively associated with change in AR and MR. CONCLUSIONS: Intrareader agreement was substantial for AR and MR. Components of total test-retest variability found were reader, biological (change in diastolic blood pressure), and regression to the mean. Recommendations for clinical practice include monitoring blood pressure changes and understanding the confidence limits of the clinical test. Test-retest variability and its components should be considered in echocardiography and other diagnostic testing.