Sonal Chandra

Characterization of degenerative mitral valve disease using morphologic analysis of real-time three-dimensional echocardiographic images: objective insight into complexity and planning of mitral valve repair.

Background—Presurgical planning of mitral valve (MV) repair in patients with Barlow disease (BD) and fibroelastic deficiency (FED) is challenging because of the inability to assess accurately the complexity of MV prolapse. We hypothesized that the etiology of degenerative MV disease (DMVD) could be objectively and accurately ascertained using parameters of MV geometry obtained by morphological analysis of real-time 3D echocardiographic (RT3DE) images. Methods and Results—Seventy-seven patients underwent transesophageal RT3DE study: 57 patients with DMVD studied intraoperatively (28 BD, 29 FED classified during surgery) and 20 patients with normal MV who were used as control subjects (NL). MVQ software (Philips) was used to measure parameters of annular dimensions and geometry and leaflet surface area, including billowing volume and height. The Student t test and multinomial logistic regression was performed to identify parameters best differentiating DMVD patients from normal as well as FED from BD. Morphological analysis in the DMVD group revealed a progressive increase in multiple parameters from NL to FED to BD, allowing for accurate diagnosis of these entities. The strongest predictors of the presence of DMVD included billowing height and volume. Three-dimensional billowing height with a cutoff value of 1.0 mm differentiated DMVD from NL without overlap, and billowing volume with a cutoff value 1.15 mL differentiated between FED and BD without overlap. Conclusions—Morphological analysis as a form of decision support in assessing MV billowing revealed significant quantifiable differences between NL, FED, and BD patients, allowing accurate classification of the etiology of MV prolapse and determination of the anticipated complexity of repair.Pre-surgical planning of mitral valve (MV) repair in patients with Barlows disease (BD) and fibroelastic deficiency (FED) is challenging due to inability to accurately assess the complexity of MV prolapse. We hypothesized that the etiology of degenerative MV disease (DMVD) could be objectively and accurately determined using morphologic analysis of MV geometry from real-time 3D echocardiographic (RT3DE) images. Seventy-seven patients underwent transesophageal RT3DE study: 57 patients with DMVD studied intra-operatively (28 BD, 29 FED classified during surgery) and 20 patients with normal MV who were used as controls (NL). Parameters of annular dimensions and geometry, and leaflet surface area were measured. Morphologic analysis in the DMVD group revealed a progressive increase in multiple parameters from NL to FED to BD, allowing for accurate diagnosis of these entities. Strongest predictors of the presence of DMVD included billowing height and volume. 3D billowing height with a cutoff value of 1.0 mm differentiated DMVD from NL without overlap, and billowing volume with a cutoff value 1.15 ml differentiated between FED and BD without overlap. Morphologic analysis as a form of decision support of assessing MV billowing revealed significant quantifiable differences between NL, FED and Barlow, allowing accurate classification of the etiology of MV prolapse and determination of the anticipated complexity of repair‥

Late gadolinium enhancement cardiovascular magnetic resonance predicts clinical worsening in patients with pulmonary hypertension

BackgroundLate gadolinium enhancement (LGE) occurs at the right ventricular (RV) insertion point (RVIP) in patients with pulmonary hypertension (PH) and has been shown to correlate with cardiovascular magnetic resonance (CMR) derived RV indices. However, the prognostic role of RVIP-LGE and other CMR-derived parameters of RV function are not well established. Our aim was to evaluate the predictive value of contrast-enhanced CMR in patients with PH.MethodsRV size, ejection fraction (RVEF), and the presence of RVIP-LGE were determined in 58 patients with PH referred for CMR. All patients underwent right heart catheterization, exercise testing, and N-terminal pro-brain natriuretic peptide (NT-proBNP) evaluation; results of which were included in the final analysis if performed within 4 months of the CMR study. Patients were followed for the primary endpoint of time to clinical worsening (death, decompensated right ventricular heart failure, initiation of prostacyclin, or lung transplantation).ResultsOverall, 40/58 (69%) of patients had RVIP-LGE. Patients with RVIP- LGE had larger right ventricular volume index, lower RVEF, and higher mean pulmonary artery pressure (mPAP), all p < 0.05. During the follow-up period of 10.2 ± 6.3 months, 19 patients reached the primary endpoint. In a univariate analysis, RVIP-LGE was a predictor for adverse outcomes (p = 0.026). In a multivariate analysis, CMR-derived RVEF was an independent predictor of clinical worsening (p = 0.036) along with well-established prognostic parameters such as exercise capacity (p = 0.010) and mPAP (p = 0.001).ConclusionsThe presence of RVIP-LGE in patients with PH is a marker for more advanced disease and poor prognosis. In addition, this study reveals for the first time that CMR-derived RVEF is an independent non-invasive imaging predictor of adverse outcomes in this patient population.

Characterization of Degenerative Mitral Valve Disease Using Morphologic Analysis of Real-Time 3D Echocardiographic Images: Objective Insight into Complexity and Planning of Mitral Valve Repair

Background—Presurgical planning of mitral valve (MV) repair in patients with Barlow disease (BD) and fibroelastic deficiency (FED) is challenging because of the inability to assess accurately the complexity of MV prolapse. We hypothesized that the etiology of degenerative MV disease (DMVD) could be objectively and accurately ascertained using parameters of MV geometry obtained by morphological analysis of real-time 3D echocardiographic (RT3DE) images. Methods and Results—Seventy-seven patients underwent transesophageal RT3DE study: 57 patients with DMVD studied intraoperatively (28 BD, 29 FED classified during surgery) and 20 patients with normal MV who were used as control subjects (NL). MVQ software (Philips) was used to measure parameters of annular dimensions and geometry and leaflet surface area, including billowing volume and height. The Student t test and multinomial logistic regression was performed to identify parameters best differentiating DMVD patients from normal as well as FED from BD. Morphological analysis in the DMVD group revealed a progressive increase in multiple parameters from NL to FED to BD, allowing for accurate diagnosis of these entities. The strongest predictors of the presence of DMVD included billowing height and volume. Three-dimensional billowing height with a cutoff value of 1.0 mm differentiated DMVD from NL without overlap, and billowing volume with a cutoff value 1.15 mL differentiated between FED and BD without overlap. Conclusions—Morphological analysis as a form of decision support in assessing MV billowing revealed significant quantifiable differences between NL, FED, and BD patients, allowing accurate classification of the etiology of MV prolapse and determination of the anticipated complexity of repair.Pre-surgical planning of mitral valve (MV) repair in patients with Barlows disease (BD) and fibroelastic deficiency (FED) is challenging due to inability to accurately assess the complexity of MV prolapse. We hypothesized that the etiology of degenerative MV disease (DMVD) could be objectively and accurately determined using morphologic analysis of MV geometry from real-time 3D echocardiographic (RT3DE) images. Seventy-seven patients underwent transesophageal RT3DE study: 57 patients with DMVD studied intra-operatively (28 BD, 29 FED classified during surgery) and 20 patients with normal MV who were used as controls (NL). Parameters of annular dimensions and geometry, and leaflet surface area were measured. Morphologic analysis in the DMVD group revealed a progressive increase in multiple parameters from NL to FED to BD, allowing for accurate diagnosis of these entities. Strongest predictors of the presence of DMVD included billowing height and volume. 3D billowing height with a cutoff value of 1.0 mm differentiated DMVD from NL without overlap, and billowing volume with a cutoff value 1.15 ml differentiated between FED and BD without overlap. Morphologic analysis as a form of decision support of assessing MV billowing revealed significant quantifiable differences between NL, FED and Barlow, allowing accurate classification of the etiology of MV prolapse and determination of the anticipated complexity of repair‥

Valvular heart disease. The value of 3-dimensional echocardiography.

Significant advances in 3-dimensional echocardiography (3DE) technology have ushered its use into clinical practice. The recent advent of real-time 3DE using matrix array transthoracic and transesophageal transducers has resulted in improved image spatial resolution, and therefore, enhanced visualization of the pathomorphological features of the cardiac valves compared with previously used sparse array transducers. It has enabled an unparalleled real-time visualization of valves and subvalvular anatomic features from a single volume acquisition without the need for offline reconstruction. On-cart or offline post-processing using commercially available and custom 3-dimensional analysis software allows the quantification of multiple parameters, such as orifice area, prolapse height and volume in mitral valve disease, area of the left ventricular outflow tract, and tricuspid annular geometry. In this review, we discuss the incremental role of 3DE in evaluating valvular anatomic features, volumetric quantification, pre-surgical planning, intraprocedural guidance, and post-procedural assessment of valvular heart disease.

Evaluation of the American College of Cardiology Foundation/American Society of Nuclear Cardiology appropriateness criteria for SPECT myocardial perfusion imaging.

Background. The American College of Cardiology Foundation/American Society of Nuclear Cardiology appropriateness criteria (AC) were created to guide responsible use of single photon emission computed tomography (SPECT). Clinical applicability of the AC has not been evaluated.Methods and Results. Indications for testing were determined in 1209 patients and categorized as having appropriate, uncertain, or inappropriate indications; the specialty of the ordering physician was noted. There were 940 (80%) appropriate, 154 (13%) inappropriate, and 79 (7%) uncertain tests; 36 tests were labeled “no category,” as these were ordered for indications not clearly addressed in the AC. Inappropriate studies had more normal and lower summed stress scores, although there remained a high proportion of abnormal SPECT studies in this group (26% of women and 50% of men). Women had lower summed stress scores and more normal tests in the appropriate and inappropriate groups. Studies ordered by anesthesiologists for preoperative evaluation were more likely to be deemed inappropriate than other specialty groups.Conclusion. In evaluating the AC in a single-center academic setting, the majority of studies are appropriate, but a large proportion of ordered SPECT studies were categorized as uncertain, inappropriate, or no category. Although the inappropriate studies showed less ischemia than other groups, especially in women, a substantial portion of these studies (32%) were abnormal.

Myocardial damage in patients with sarcoidosis and preserved left ventricular systolic function: an observational study

Late gadolinium enhanced cardiovascular magnetic resonance (LGE‐CMR) is a valuable test to detect myocardial damage in patients with sarcoidosis; however, the clinical significance of LGE in sarcoidosis patients with preserved left ventricular ejection fraction (LVEF) is not defined. We aim to characterize the prevalence of LGE, its associated cardiac findings, and its clinical implications in sarcoidosis patients with preserved LVEF.

United States Validation of the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR)

BACKGROUND The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) is the first pulmonary hypertension-specific instrument for assessing patient-reported symptoms, functioning, and quality of life. To enable use in the United States, this study adapted, field-tested, and evaluated its reliability and validity at a single center in Chicago. METHODS A lay panel confirmed appropriate wording of CAMPHOR for United States patients, and 15 patients with pulmonary hypertension field-tested the CAMPHOR for face and content validity. A postal validation study, with the Medical Outcomes Study Short Form 36 (SF-36) Health Survey as a comparator, was sent to patients on 2 occasions, 2 weeks apart. World Health Organization (WHO) functional class and 6-minute walk test data were obtained. RESULTS Field-test interviews found the CAMPHOR relevant and comprehensible. A total of 147 patients (84.0% women) with a mean of 50 +/- 14.6 years participated in the validation study. The new scales had good test-retest reliability (range, 0.80-0.95) and internal consistency (range, 0.78-0.95). The CAMPHOR scales correlated with the SF-36 and 6-minute walk test. Patients in WHO functional class III had worse scores than those in class II (p = 0.02), as did patients who rated their health worse (p < 0.001). CONCLUSIONS The US CAMPHOR is a reliable and valid measure of quality of life and health status in pulmonary hypertension and can be recommended for use in clinical practice and trials in the United States.

A three-dimensional insight into the complexity of flow convergence in mitral regurgitation: adjunctive benefit of anatomic regurgitant orifice area

Mitral effective regurgitant orifice area (EROA) using the flow convergence (FC) method is used to quantify the severity of mitral regurgitation (MR). However, it is challenging and prone to interobserver variability in complex valvular pathology. We hypothesized that real-time three-dimensional (3D) transesophageal echocardiography (RT3D TEE) derived anatomic regurgitant orifice area (AROA) can be a reasonable adjunct, irrespective of valvular geometry. Our goals were to 1) to determine the regurgitant orifice morphology and distance suitable for FC measurement using 3D computational flow dynamics and finite element analysis (FEA), and (2) to measure AROA from RT3D TEE and compare it with 2D FC derived EROA measurements. We studied 61 patients. EROA was calculated from 2D TEE images using the 2D-FC technique, and AROA was obtained from zoomed RT3DE TEE acquisitions using prototype software. 3D computational fluid dynamics by FEA were applied to 3D TEE images to determine the effects of mitral valve (MV) orifice geometry on FC pattern. 3D FEA analysis revealed that a central regurgitant orifice is suitable for FC measurements at an optimal distance from the orifice but complex MV orifice resulting in eccentric jets yielded nonaxisymmetric isovelocity contours close to the orifice where the assumptions underlying FC are problematic. EROA and AROA measurements correlated well (r = 0.81) with a nonsignificant bias. However, in patients with eccentric MR, the bias was larger than in central MR. Intermeasurement variability was higher for the 2D FC technique than for RT3DE-based measurements. With its superior reproducibility, 3D analysis of the AROA is a useful alternative to quantify MR when 2D FC measurements are challenging.

Carbon monoxide diffusing capacity and mortality in pulmonary arterial hypertension

BACKGROUND Abnormal carbon monoxide diffusing capacity (DLCO) is a marker of pulmonary vascular disease and predicts the presence of pulmonary arterial hypertension (PAH) and poor prognosis in diseases such as systemic sclerosis and idiopathic pulmonary fibrosis. Little is known of its prognostic utility in World Health Organization (WHO) Group I PAH. METHODS We performed a cohort study of 408 patients with WHO Group I PAH from 1982 to 2006, with data on demographics, comorbidities, medications, functional class, laboratory tests, exercise testing, and hemodynamics. DLCO was determined upon entry into the study. We divided the cohort into tertiles based on DLCO and compared differences between groups. We used a Cox proportional hazards analysis to determine the association of DLCO with mortality, after adjusting for age, connective tissue disease etiology, functional class, pulmonary function testing variables, serum creatinine, albumin, hemoglobin, lung parenchymal abnormalities on chest computed tomography, oxygen use, and hemodynamic variables. RESULTS The lowest tertile of DLCO was independently associated with an increased risk of death (univariate hazard ratio [HR] = 2.7, 95% confidence interval [CI] 1.9 to 3.9, p < 0.0001; multivariate HR = 2.4, 95% CI 1.1 to 5.0, p = 0.025). On receiving operator characteristic (ROC) curve analysis, the c-statistic for the multivariate model without DLCO was 0.75, whereas the c-statistic for the multivariate model with DLCO was 0.78 (p = 0.003 by likelihood ratio test). Importantly, a multivariate model with hemodynamic variables alone (c-statistic = 0.61) was quite inferior to the multivariate model, which included DLCO. CONCLUSION DLCO is an independent predictor of death in patients with WHO Group I PAH.

Antirestenotic Effects of a Locally Delivered Caspase Inhibitor in a Balloon Injury Model

Background—The precise role of arterial barotrauma-mediated apoptosis in causing restenosis is unclear. The purpose of this study was to determine if a link exists between angioplasty-mediated medial smooth muscle cell apoptosis and subsequent neointimal hyperplasia. Methods and Results—Bilateral iliac artery angioplasty was performed in 25 male New Zealand White rabbits. Simultaneous with balloon injury, each artery was treated locally with either the caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp(Ome)-fluoromethylketone (ZVAD-fmk) or control. In the acute cohort that was survived to 4 hours (n=10, 7 high dose and 3 low dose), an apoptotic index was calculated using the terminal deoxynucleotidyl TUNEL method. In the intermediate cohort that was survived to 2 weeks (n=5), luminal reendothelialization was measured via CD-31 staining. In the chronic cohort that was survived to 4 weeks (n=10), neointimal area was measured. In the acute cohort, there was a 40% reduction in the apoptotic index with high-dose ZVAD-fmk (P =0.008) and a 33% reduction with low-dose ZVAD-fmk (P =0.08). At 2 weeks, there was no significant difference in the degree of luminal reendothelialization. However, at 4 weeks, there was a 33% (0.33±0.23 versus 0.22±0.20 mm2) (P <0.005) reduction in neointimal area in ZVAD-fmk–treated arteries. Conclusions—The local delivery of ZVAD-fmk during balloon injury inhibits smooth muscle cell apoptosis. This corresponds to a significant reduction in neointimal proliferation seen at 4 weeks without a significant change in the degree of reendothelialization at 2 weeks.