Nicole M. Bhave

Sample Size and Cost Analysis for Pulmonary Arterial Hypertension Drug Trials Using Various Imaging Modalities to Assess Right Ventricular Size and Function End Points

Background—Placebo-controlled trials for pulmonary arterial hypertension are no longer acceptable because new therapies must show clinically significant effects on top of standard treatment. The purpose of this study was to estimate sample sizes and imaging costs for the planning of a hypothetical pulmonary arterial hypertension drug trial using imaging to detect changes in right ventricular size and function in response to combined therapy. Methods and Results—Same-day cardiovascular MR (CMR) and 2-dimensional (2D) and 3D transthoracic echocardiography (2DTTE and 3DTTE) were performed in 22 patients with pulmonary arterial hypertension (54±13 years of age) twice, 6 months apart. Short-axis CMR cines and full-volume 3DTTE data sets of the right ventricle were used to measure end-diastolic volume and ejection fraction. Fractional area change was obtained from 2DTTE. Sample size calculations used a 2-sample t test model incorporating differences between baseline and 6-month measurements. Cost estimates were made using the Medicare fee schedule. No significant differences were noted between baseline and follow-up measurements. Large SDs reflected variable progression of disease in individual patients on standard therapy and measurement variability. These sources of variability resulted in intertechnique differences in sample sizes: to detect a change of 5% to 15% in 3DTTE-derived right ventricular ejection fraction and fractional area change or change of 15 to 30 mL in 3DTTE right ventricular end-diastolic volume; sample sizes were 2× to 2.5× those required by CMR. As a result, the total cost of a trial using complete TTE was greater than CMR, which was greater than limited TTE. Conclusions—Because of lower measurement variability, CMR is more cost saving in pulmonary arterial hypertension drug trials than echocardiography, unless limited TTE is used.

Considerations when measuring myocardial perfusion reserve by cardiovascular magnetic resonance using regadenoson

BackgroundAdenosine cardiovascular magnetic resonance (CMR) can accurately quantify myocardial perfusion reserve. While regadenoson is increasingly employed due to ease of use, imaging protocols have not been standardized. We sought to determine the optimal regadenoson CMR protocol for quantifying myocardial perfusion reserve index (MPRi) – more specifically, whether regadenoson stress imaging should be performed before or after rest imaging.MethodsTwenty healthy subjects underwent CMR perfusion imaging during resting conditions, during regadenoson-induced hyperemia (0.4 mg), and after 15 min of recovery. In 10/20 subjects, recovery was facilitated with aminophylline (125 mg). Myocardial time-intensity curves were used to obtain left ventricular cavity-normalized myocardial up-slopes. MPRi was calculated in two different ways: as the up-slope ratio of stress to rest (MPRi-rest), and the up-slope ratio of stress to recovery (MPRi-recov).ResultsIn all 20 subjects, MPRi-rest was 1.78 ± 0.60. Recovery up-slope did not return to resting levels, regardless of aminophylline use. Among patients not receiving aminophylline, MPRi-recov was 36 ± 16% lower than MPRi-rest (1.13 ± 0.38 vs. 1.82 ± 0.73, P = 0.001). In the 10 patients whose recovery was facilitated with aminophylline, MPRi-recov was 20 ± 24% lower than MPRi-rest (1.40 ± 0.35 vs. 1.73 ± 0.43, P = 0.04), indicating incomplete reversal. In 3 subjects not receiving aminophylline and 4 subjects receiving aminophylline, up-slope at recovery was greater than at stress, suggesting delayed maximal hyperemia.ConclusionsMPRi measurements from regadenoson CMR are underestimated if recovery perfusion is used as a substitute for resting perfusion, even when recovery is facilitated with aminophylline. True resting images should be used to allow accurate MPRi quantification. The delayed maximal hyperemia observed in some subjects deserves further study.Trial registrationClinicalTrials.gov NCT00871260

Right Ventricular Strain in Pulmonary Arterial Hypertension: A 2D Echocardiography and Cardiac Magnetic Resonance Study

Right ventricular (RV) strain is a potentially useful prognostic marker in patients with pulmonary arterial hypertension (PAH). However, published reports regarding the accuracy of two‐dimensional echocardiography (2DE)‐derived RV strain against an independent reference in this patient population are limited. The aims of this study were: (1) to study the relationship between 2DE RV longitudinal strain and cardiovascular magnetic resonance (CMR)‐derived RV ejection fraction (RVEF) in patients with PAH; (2) to compare 2DE‐derived and CMR‐derived RV longitudinal strain in these patients; and (3) to determine the reproducibility of these measurements.

Evaluation of left ventricular structure and function by three-dimensional echocardiography.

Purpose of reviewTo summarize research on the use of 3-dimensional (3D) echocardiography for quantifying left ventricular (LV) volumes, ejection fraction, and mass, and to describe emerging applications of the technology. Recent findingsSeveral publications have provided reference values for LV volumes and ejection fraction by 3D transthoracic echocardiography (3DTTE) in normal patients. SummaryWith real-time 3DTTE, one can acquire and display a 3D image encompassing the entire LV within seconds. Because 3DTTE aids in identification of the true LV apex, it provides more accurate LV volumes than its 2D counterpart. As compared with a cardiovascular magnetic resonance standard, 3DTTE tends to slightly underestimate LV volumes, in part because its spatial resolution is limited, making identification of the true endocardial border more difficult. As compared with 2DTTE, 3DTTE is advantageous for identifying and assessing the extent of regional wall motion abnormalities. For quantification of LV mass, 3DTTE is superior to both 2DTTE and M-mode echocardiography. Emerging applications of 3DTTE include speckle-tracking strain assessment, dyssynchrony analysis, and LV shape analysis, which appear to have prognostic value in patients with a variety of cardiac conditions.

Analysis of myocardial perfusion from vasodilator stress computed tomography: Does improvement in image quality by iterative reconstruction lead to improved diagnostic accuracy?

BACKGROUND Iterative reconstruction (IR) in cardiac CT has been shown to improve confidence of interpretation of noninvasive coronary CT angiography (CTA). OBJECTIVE We hypothesized that IR would also improve the quality of vasodilator stress coronary CT images acquired with low tube voltage to assess myocardial perfusion and the accuracy of the detection of perfusion abnormalities by using quantitative 3-dimensional (3D) analysis. METHODS We studied 39 consecutive patients referred for coronary CTA (256-slice scanner; Philips), who underwent additional imaging (100 kV, prospective gating) with regadenoson (0.4 mg; Astellas). Stress images were reconstructed with different algorithms: filtered back projection (FBP) and IR (iDose; Philips). Image quality was quantified by signal-to-noise and contrast-to-noise ratios in the blood pool and the myocardium. Then, FBP and separately IR images were analyzed with custom 3D analysis software to quantitatively detect perfusion defects. Accuracy of detection was compared with perfusion abnormalities predicted by coronary stenosis >50% on coronary CTA. RESULTS Five patients with image artifacts were excluded. In the remaining 34 patients, both signal-to-noise and contrast-to-noise ratios increased with IR, indicating improvement in image quality compared with FBP. For 3D perfusion analysis, 10 patients with normal coronary arteries were used as a reference to correct for x-ray attenuation variations in normal myocardium. In the remaining 24 patients, reduced noise levels in the IR images compared with FBP resulted in tighter attenuation distribution and improved detection of perfusion abnormalities. CONCLUSION IR significantly improves image quality on regadenoson stress CT images acquired with low tube voltage, leading to improved 3D quantitative evaluation of myocardial perfusion.

Myocardial Perfusion Imaging with Cardiac Computed Tomography: State of the Art

Cardiac computed tomography (CCT) has become an important tool for the anatomic assessment of patients with suspected coronary disease. Its diagnostic accuracy for detecting the presence of underlying coronary artery disease and ability to risk stratify patients are well documented. However, the role of CCT for the physiologic assessment of myocardial perfusion during resting and stress conditions is only now emerging. With the addition of myocardial perfusion imaging to coronary imaging, CCT has the potential to assess both coronary anatomy and its functional significance with a single non-invasive test. In this review, we discuss the current state of CCT myocardial perfusion imaging for the detection of myocardial ischemia and myocardial infarction and examine its complementary role to CCT coronary imaging.

Percutaneous Transcatheter Closure of the Native Aortic Valve to Treat De Novo Aortic Insufficiency After Implantation of a Left Ventricular Assist Device

A 54-year-old female with a HeartMate II (Thoratec, Pleasanton, California) left ventricular assist device (LVAD) presented 3 months after implantation with new-onset severe aortic insufficiency (AI) and cardiogenic shock. A reoperation for surgical aortic valve closure was too high risk, so the

Echocardiographic assessment and clinical management of tricuspid regurgitation.

The evaluation and management of tricuspid regurgitation (TR) are often challenging. Significant TR is an independent predictor of reduced event-free and overall survival. Therefore, an evidence-based approach to the diagnosis and treatment of TR is of critical importance. TR can be classified into two basic categories: primary and secondary TR. The former refers to conditions in which the primary pathophysiologic process affects the valve itself, whereas the latter is much more common and occurs due to tricuspid annular dilatation, right heart failure, and/or pulmonary hypertension. Two- and three-dimensional echocardiography allow for a comprehensive assessment of TR severity and mechanisms. In patients with fixed pulmonary hypertension and right ventricular dysfunction, medical management of TR is generally preferable. In patients undergoing mitral valve surgery, tricuspid annular dilatation should trigger prophylactic tricuspid valve repair, regardless of the degree of TR. Future efforts in TR management will include development of percutaneous repair procedures.

Right atrial strain is predictive of clinical outcomes and invasive hemodynamic data in group 1 pulmonary arterial hypertension

Transthoracic echocardiography (TTE) is a practical and widely used tool for risk stratification in pulmonary arterial hypertension (PAH). We hypothesized that right atrial (RA) reservoir function, represented by peak RA systolic strain, correlates with invasive hemodynamic measurements and clinical outcomes in PAH. Patients with group 1 PAH who had TTE within 6 months of index PAH clinic visit and right heart catheterization were included in this retrospective study. Peak RA strain in the 2D apical 4-chamber view was measured with speckle-tracking software. The primary endpoint was a composite of prostacyclin initiation, lung transplantation, and death. RA strain was also measured in healthy control subjects. Among the 37 patients studied, 25 (68%) met the primary endpoint. RA strain was significantly lower among patients who met the primary endpoint than among those who did not (mean 20% vs. 33%, P = 0.002). Strain was lower in PAH patients than in controls (mean 24% vs. 35%, P = 0.0001). RA strain correlated negatively with hemodynamic data including RA pressure (R = −0.31), mean pulmonary arterial pressure (R = −0.33), and pulmonary vascular resistance (R = −0.39), and positively with cardiac index (R = 0.44). In receiver operating characteristic analysis to distinguish between patients meeting the primary endpoint and event-free survivors, RA strain was not significantly different from RA volume, right ventricular (RV) fractional area change, RV basal diameter, or right ventricular systolic pressure (area under the curve 0.82, 0.81, 0.83, 0.86, and 0.97, respectively). Our results demonstrate that RA strain is predictive of clinical outcomes in PAH. Further research is needed to determine if RA strain is independently associated with outcomes in this population.

FULLY AUTOMATED QUANTIFICATION OF LEFT VENTRICULAR AND LEFT ATRIAL VOLUMES FROM TRANSTHORACIC 3D ECHOCARDIOGRAPHY: A VALIDATION STUDY

Cardiac chamber quantification from 3D transthoracic echocardiography (3D TTE) has been shown to be superior to measurements obtained from 2D studies. However, integration of 3D TTE into routine clinical practice has been limited by the time-consuming workflow and need for 3D expertise. We assessed