Mathieu Bernier

Safety of Contrast Agent Use During Stress Echocardiography: A 4-Year Experience From a Single-Center Cohort Study of 26,774 Patients

OBJECTIVES We evaluated the short- and long-term safety of contrast agents during stress echocardiography (SE). BACKGROUND Concerns about contrast agent safety led to revised recommendations for product use in the U.S. METHODS We studied 26,774 patients who underwent SE between November 1, 2003, and December 31, 2007. The 10,792 patients who comprised the contrast cohort received second-generation perfluorocarbon-based agents for left ventricular opacification during SE. The noncontrast cohort comprised 15,982 patients who had their first SE in the same period but without contrast agents. Short-term (< or = 72 h and < or = 30 days) and long-term (up to 4.5 years) end points were death and myocardial infarction (MI). Cox regression models were used. Immediate contrast agent-related adverse effects were also reported. RESULTS The contrast cohort had older patients (mean [SD] age, 65.8 [12.1] years vs. 62.6 [14.1] years; p < 0.001), a higher percentage of males (57.4% vs. 52.8%, p < 0.001), and higher-risk patients compared with the noncontrast cohort. In addition, dobutamine SE patients had greater cardiac risk than exercise SE patients. Abnormal SE findings in patients who received contrast agents were more frequent (32.4% vs. 27.9%, p < 0.001). The 2 cohorts had no statistical difference in the incidence of short-term events (death and MI). Within 72 h, 1 patient in the contrast cohort and 2 patients in the noncontrast cohort died (p = 0.54); 3 in the contrast cohort and 7 in the noncontrast cohort had MI (p = 0.92). Within 30 days, 37 patients (0.34%) in the contrast cohort and 57 patients (0.36%) in the noncontrast cohort died (p = 0.85); 17 patients (0.16%) in the contrast cohort and 16 patients (0.10%) in the noncontrast cohort had MI (p = 0.19). Adjusted hazard ratios were not different between cohorts for death (0.99; 95% confidence interval: 0.88 to 1.11) or MI (0.99; 95% confidence interval: 0.80 to 1.22). CONCLUSIONS The use of contrast agents during SE was not associated with an increased short-term or long-term risk of death or MI.

Microvascular Function in Takotsubo Cardiomyopathy With Contrast Echocardiography: Prospective Evaluation and Review of Literature

BACKGROUND Takotsubo cardiomyopathy (TC) mimics ST-elevation myocardial infarction without substantial angiographic stenosis. Coronary microvascular dysfunction has been proposed as a possible mechanism in TC. The aim of this study was to evaluate microvascular function in TC using real-time myocardial contrast echocardiography (MCE). METHODS Real-time MCE was performed within 24 hours of coronary angiographic diagnosis of TC. Myocardial perfusion was evaluated through qualitative and quantitative myocardial contrast echocardiographic analyses comparing normal segments with segments with dysfunctional wall motion (WM). RESULTS From January 2007 to January 2008, 11 patients received diagnoses of TC. Of these patients, 9 were prospectively enrolled (mean age, 70.9 +/- 17.5 years; 8 women). Qualitative and quantitative myocardial contrast echocardiographic analyses were feasible in 87% and 81% of segments. Overall, concordance between qualitative MCE and WM for normal versus abnormal analysis was observed in 71% of segments (kappa = 0.442, SE = 0.08). Significantly lower myocardial blood flow velocity (beta) and lower myocardial blood flow (Abeta) were detected in segments with dysfunctional WM compared with those with normal WM (beta = 0.55 +/- 0.39 vs 0.90 +/- 0.77, P = .009; Abeta = 5.31 +/- 3.92 vs 12.38 +/- 13.47, P = .002). In the discordant segments between qualitative MCE and WM, the quantitative perfusion parameters beta and Abeta were significantly lower in segments with dysfunctional WM compared with those with normal WM (beta = 0.22 +/- 0.20 vs 1.79 +/- 0.57, P = .01; Abeta = 1.90 +/- 1.1 vs 24.29 +/- 19.9, P = .02). Recovery of WM abnormalities was detected in all patients during follow-up echocardiography (mean, 60.3 +/- 66.0 days). No contrast-related side effects were reported. During mean follow-up of 5.9 +/- 4.6 months, there were no cardiac events, but 1 noncardiac death (from lung cancer) occurred. CONCLUSION TC is associated with abnormal myocardial perfusion detected with qualitative and quantitative MCE, indicative of microvascular dysfunction.

Safety of Contrast Agent Use during Stress Echocardiography in Patients with Elevated Right Ventricular Systolic Pressure: A Cohort Study

Background—Microbubble safety concerns led to changes in product recommendations for patients with pulmonary hypertension. Noninvasive estimation of right ventricular systolic pressure (RVSP) is equivalent to pulmonary artery systolic pressure in the absence of pulmonary outflow obstruction. We analyzed the short- and long-term outcomes of patients who received microbubble contrast and those who did not during stress echocardiography (SE) according to resting RVSP. Methods and Results—From November 2003 to December 2007, 26 774 patients underwent SE. RVSP (mean, 32.6±9.6 mm Hg) was measured in 16 434 patients. Of these, 6164 (37.5%) received contrast for left ventricular opacification and 10 270 (62.5%) did not. Short-term (≤72 hours and ≤30 days) and long-term (4.3 years) end points were death and myocardial infarction. Analysis was done for rest RVSP cut-points ≥35, ≥50, and ≥60 mm Hg and tricuspid regurgitant velocities ≥2.7 ms−1 and ≥3.5 ms−1. Adjusted Cox regression models were used. The contrast cohort comprised older patients (age, 67±12 versus 64±14 years; P<0.001), who were more likely to have positive SE results (35% versus 30%, P<0.001) compared with the noncontrast cohort. Using RVSP ≥50 mm Hg, there was no significant difference in short-term events between the contrast and noncontrast cohorts. For long-term events, there was no significant difference between both cohorts (adjusted hazard ratios [95% confidence intervals] for death, 1.10 [0.80 to 1.50], P=0.56; and myocardial infarction, 0.34 [0.11 to 1.03], P=0.06). Similar results were obtained at different RVSP and tricuspid regurgitant cut-points. Contrast agent-related adverse effects occurred in <1% of patients. Conclusion—RVSP had no impact on predisposition to adverse outcomes in patients undergoing contrast SE in the population studied.

Myocardial contrast echocardiography in biopsy-proven primary cardiac amyloidosis

Cardiac vasculature is affected in 88-90% of patients with primary cardiac amyloidosis (CA). Myocardial contrast echocardiography (MCE) relies on the ultrasound detection of microbubble contrast agents that are solely confined to the intravascular space, and are therefore useful in the evaluation of flow in the microvasculature. This is the first case report describing the use of MCE during vasodilator stress to evaluate coronary flow reserve in a patient with biopsy-proven primary CA and angiographically normal coronaries. Qualitative MCE demonstrated delayed replenishment of microbubbles during peak stress; quantitative analysis was consistent with a reduction in total myocardial blood flow and reserve values. Comparative imaging modalities including strain and strain rate imaging, magnetic resonance imaging, and myocardial scintigraphy were suggestive to the diagnosis of CA. In conclusion, MCE is a method for recognition of microvascular dysfunction, and might be considered as a useful tool to augment echocardiographic assessment in the early diagnosis of CA.

Quantitative myocardial contrast echocardiography during pharmacological stress for diagnosis of coronary artery disease: a systematic review and meta-analysis of diagnostic accuracy studies.

AIMS We conducted a meta-analysis to evaluate the accuracy of quantitative stress myocardial contrast echocardiography (MCE) in coronary artery disease (CAD). METHODS AND RESULTS Database search was performed through January 2008. We included studies evaluating accuracy of quantitative stress MCE for detection of CAD compared with coronary angiography or single-photon emission computed tomography (SPECT) and measuring reserve parameters of A, beta, and Abeta. Data from studies were verified and supplemented by the authors of each study. Using random effects meta-analysis, we estimated weighted mean difference (WMD), likelihood ratios (LRs), diagnostic odds ratios (DORs), and summary area under curve (AUC), all with 95% confidence interval (CI). Of 1443 studies, 13 including 627 patients (age range, 38-75 years) and comparing MCE with angiography (n = 10), SPECT (n = 1), or both (n = 2) were eligible. WMD (95% CI) were significantly less in CAD group than no-CAD group: 0.12 (0.06-0.18) (P < 0.001), 1.38 (1.28-1.52) (P < 0.001), and 1.47 (1.18-1.76) (P < 0.001) for A, beta, and Abeta reserves, respectively. Pooled LRs for positive test were 1.33 (1.13-1.57), 3.76 (2.43-5.80), and 3.64 (2.87-4.78) and LRs for negative test were 0.68 (0.55-0.83), 0.30 (0.24-0.38), and 0.27 (0.22-0.34) for A, beta, and Abeta reserves, respectively. Pooled DORs were 2.09 (1.42-3.07), 15.11 (7.90-28.91), and 14.73 (9.61-22.57) and AUCs were 0.637 (0.594-0.677), 0.851 (0.828-0.872), and 0.859 (0.842-0.750) for A, beta, and Abeta reserves, respectively. CONCLUSION Evidence supports the use of quantitative MCE as a non-invasive test for detection of CAD. Standardizing MCE quantification analysis and adherence to reporting standards for diagnostic tests could enhance the quality of evidence in this field.

Effects of chronic sildenafil use on pulmonary hemodynamics and clinical outcomes in heart transplantation.

BACKGROUND Elevated pulmonary vascular resistance (PVR) in heart transplant (HT) candidates is associated with poor survival after HT. This study assessed the effect of peri-operative sildenafil administration on pulmonary hemodynamics and clinical outcomes in patients with advanced heart failure who were considered high-risk for HT because of elevated PVR and transpulmonary gradient (TPG). METHODS The study included 119 consecutive patients who underwent HT between 2004 and 2011. Fifteen patients (Group A) had severe pulmonary hypertension (PH), defined as mean pulmonary pressure (MPAP)>25 mm Hg and PVR>2.5 Wood units (WU), and/or TPG>12 mm Hg after vasodilator test or the continuous administration of inotropics drugs, and 104 patients (Group B) were without severe PH. Group A received sildenafil therapy. Pulmonary hemodynamics were evaluated before HT with and without sildenafil therapy. Right catheterization was performed early after HT with sildenafil therapy and late after HT without sildenafil. Survival after HT was compared between the groups. RESULTS The sildenafil dosage was 109±42 mg/day during 163±116 days before HT. After sildenafil therapy MPAP, PVR, and TPG decreased from 43.9±12.5 to 33.4±5.8 mm Hg, 5.0±1.1 to 3.0±1.6 WU, and 17.3±3.2 to 10.2±4.1 mm Hg, respectively (p<.01). All patients underwent successful HT. Sildenafil dosage was 140±70 mg/day for 43±45 days after HT. There were no differences in PVR and TPG with sildenafil therapy early after HT and without sildenafil 6 months after HT. Survival after HT was similar between the groups. CONCLUSION Sildenafil therapy before and after HT in patients with severe PH is associated with improved pulmonary hemodynamics and successful HT, without an increase in post-HT mortality.

Assessment of Myocardial Perfusion during Adenosine Stress Using Real Time Three‐Dimensional and Two‐Dimensional Myocardial Contrast Echocardiography: Comparison with Single‐Photon Emission Computed Tomography

Objectives: To evaluate diagnostic accuracy of adenosine two‐dimensional and three‐dimensional myocardial contrast echocardiography (2D‐ and 3D‐MCE) compared with single‐photon emission computed tomography (SPECT) for assessing myocardial perfusion. Methods: From January through August 2007, patients with known or suspected CAD who were referred for SPECT underwent simultaneous adenosine 2D‐MCE and 3D‐MCE (live and full volume [FV]). Perfusion and wall motion in 17 segments in the left anterior descending, left circumflex, and right coronary artery territories were analyzed. Results: We studied 30 patients: mean (SD) age, 72.6 (8.2) years; 19 (63%) men. Perfusion by SPECT was abnormal in 13 patients (43%). When comparing MCE with SPECT, sensitivity was comparable for 2D‐MCE, 92%; live 3D‐MCE, 91%; and FV 3D‐MCE, 90%. Specificity was comparable for 2D‐MCE, 75%; live 3D‐MCE, 69%; and FV 3D‐MCE, 79%. Agreement between live 3D‐MCE and 2D‐MCE was 92% (κ[SE], 0.83 [0.17]) and between FV 3D‐MCE and 2D‐MCE, 88% (κ[SE], 0.76 [0.13]). For eight patients in whom SPECT showed reversible defects, live 3D‐MCE correctly identified defects in seven (88%), whereas FV 3D‐MCE correctly identified them in five (63%) (P = 0.57). Conclusion: Myocardial perfusion assessment is feasible by 3D‐MCE with the advantage of rapid, facile acquisition and offline image manipulation. (Echocardiography 2010;27:421‐429)

Diagnostic accuracy of contrast echocardiography during adenosine stress for detection of abnormal myocardial perfusion: a prospective comparison with technetium-99 m sestamibi single-photon emission computed tomography

Myocardial contrast echocardiography (MCE) utilizes compressible microbubbles behaving similarly to red blood cells. Destruction of microbubbles and observation of the gradual refill into the myocardium are key to evaluating perfusion using real-time MCE. We aimed to assess the feasibility and diagnostic accuracy of qualitative MCE utilizing a 17-segment model for localization of myocardial perfusion abnormalities compared with simultaneous technetium-99 m sestamibi single-photon emission computed tomography (SPECT). From July 2005 through August 2007, 97 patients with known or suspected coronary artery disease underwent simultaneous SPECT and realtime MCE during adenosine stress. Qualitative MCE and tracer uptake were analyzed visually using a 17-segment model in a blinded manner. Diagnostic accuracy and 95% confidence interval (CI) were determined. Myocardial contrast echocardiography was completed in 91 patients (age, mean [SD], 69.3 [10.9] years; body mass index, 30.0 [6.3]; 59 males [65%]). Myocardial contrast echocardiography analysis was feasible in 88 (97%) patients (261 of 264 [99%] territories; 1299 of 1497 [87%] segments). At patient level, MCE sensitivity was 88% (95% CI, 79%–94%); specificity was 85% (77%–90%). For disease detection in individual coronary territories, sensitivity and specificity were 84% (71%–92%) and 79% (72%–84%) for the left anterior descending artery; 62% (38%–80%) and 88% (83%–91%) for the left circumflex artery; and 73% (57%–82%) and 94% (89%–97%) for the right coronary artery. For MCE combined with wall-motion analysis, concordance with SPECT improved from 80% to 86%. Myocardial contrast echocardiography interobserver concordance was 81% (κ [SE], 0.611 [0.78]). Myocardial contrast echocardiography accuracy was comparable in patients classified in accordance with presence of diabetes mellitus, myocardial infarction, hypertension, or percutaneous coronary intervention. Improved MCE specificity in detecting perfusion defects was seen in patients with no history of coronary bypass graft surgery (P = 0.005). Real-time MCE with a 17-segment model for analysis has good feasibility and accuracy in evaluation of myocardial perfusion during adenosine stress.

Detection of myocardial microvascular disease using contrast echocardiography during adenosine stress in type 2 diabetes mellitus: Prospective comparison with single-photon emission computed tomography

Purrpose: To evaluate myocardial microvascular disease in patients with type 2 diabetes mellitus (DM) using myocardial contrast echocardiography (MCE) and to report on its diagnostic accuracy using single photon emission tomography (SPECT) as reference test. Methods: We prospectively enrolled 79 patients (25 DM; 66±11 years) who underwent simultaneous SPECT and MCE with contrast agent during adenosine stress. MCE and SPECT were visually analyzed using 17 segments. Quantitative MCE parameters were derived from replenishment curves. Microbubble velocity (β min−1), absolute myocardial blood flow (MBF ml/min/g), and reserve values were calculated. Diagnostic accuracy and area under curve (AUC) was reported. Results: Patients with DM had higher BMI vs non DM (33±7 vs 28±5kg/m2 P=0 .007), with more prior myocardial infarction (40 vs 15% P=.01). Visual MCE was abnormal in 40 (51%) patients (60% in DM vs 46% in non DM P=0.04). SPECT was abnormal in 38 (48%) patients [60% in DM vs 42% non DM, P=0.01]. Reserve parameters were lower in DM vs. non DM patients: (β 1.77±1.12 vs 2.20±1.4, P<0.001 and MBF 2.86± 2.62 vs. 3.67±2.84, P<0.001). DM patients without CAD on SPECT had significantly lower β, and MBF reserve compared to non DM patients without CAD. Compared to SPECT, β reserve cutoff 1.6 had AUC 0.817, sensitivity 81%, and specificity 66% while MBF reserve cutoff 1.9 had AUC 0.760, sensitivity 79%, and specificity 63% in DM patients. Conclusion: Diabetes is associated with myocardial microvascular abnormalities as evidenced by abnormal myocardial perfusion on visual and quantitative MCE.

Assessment of the Vascularity of a Left Atrial Mass Using Myocardial Perfusion Contrast Echocardiography

Emerging applications of myocardial contrast echocardiography (MCE) include the evaluation of myocardial perfusion, the improvement of the definition of intracavitary structures, and evaluation of the relative perfusion of a cardiac mass. We present a case of a patient that was found incidentally to have a cardiac mass on transthoracic echocardiography. MCE was used to evaluate the vascularity of the mass. This case is compared with another patient with a left atrial thrombus, which represents an “avascular” cardiac mass by MCE.