Asim Rafique

Aortopathy is Prevalent in Relatives of Bicuspid Aortic Valve Patients

OBJECTIVES This study aimed to determine the prevalence of dilation and abnormal elastic properties of aortic root in first-degree relatives (FDRs) of bicuspid aortic valve (BAV) patients. BACKGROUND Evidence indicates that BAV is a genetic disorder. Although FDRs of affected individuals have an increased prevalence of BAV, their risk of aortic root abnormalities is unknown. METHODS We studied dimensions as well as the elastic properties of the ascending aorta in 48 FDRs with morphologically normal tricuspid aortic valves, 54 BAV patients, and 45 control subjects using 2-dimensional echocardiography. RESULTS The prevalence of aortic root dilation was 32% in FDRs and 53% in BAV patients, whereas all control subjects showed normal aortic dimensions (p < 0.001). The FDRs and BAVs had significantly lower aortic distensibility (1.7 +/- 1.4 x 10(-3) mm Hg and 1.4 +/- 2.0 x 10(-3) mm Hg vs. 2.5 +/- 1.6 x 10(-3) mm Hg, p < 0.001) and greater aortic stiffness index (26.7 +/- 25.8 and 55.9 +/- 76.8 vs. 18.7 +/- 40.1, p = 0.001) compared with control subjects. This difference remained significant in subjects without aortic root dilation or hypertension (p = 0.002 and p = 0.004, respectively). CONCLUSIONS The aortic root is functionally abnormal and dilation is common (32%) in first-degree relatives of patients with BAV. Screening of FDRs by transthoracic 2-dimensional echocardiography should be considered for detection of aortic valve malformation and dilated ascending aorta.

The acute hemodynamic effects of MitraClip therapy.

OBJECTIVES The objective of this study was to evaluate the acute hemodynamic consequences of mitral valve (MV) repair with the MitraClip device (Abbott Vascular, Menlo Park, California). BACKGROUND Whether surgical correction of mitral regurgitation (MR) results in a low cardiac output (CO) state because of an acute increase in afterload remains controversial. The acute hemodynamic consequences of MR reduction with the MitraClip device have not been studied. METHODS We evaluated 107 patients with cardiac catheterization before and immediately following percutaneous MV repair with the MitraClip device. In addition, pre- and post-procedural hemodynamic parameters were studied by transthoracic echocardiography. RESULTS MitraClip treatment was attempted in 107 patients, and in 96 (90%) patients, a MitraClip was deployed. Successful MitraClip treatment resulted in: 1) an increase in CO from 5.0 ± 2.0 l/min to 5.7 ± 1.9 l/min (p = 0.003); 2) an increase in forward stroke volume (FSV) from 57 ± 17 ml to 65 ± 18 ml (p < 0.001); and 3) a decrease in systemic vascular resistance from 1,226 ± 481 dyn·s/cm(5) to 1,004 ± 442 dyn·s/cm(5) (p < 0.001). In addition, there was left ventricular (LV) unloading manifested by a decrease in LV end-diastolic pressure from 11.4 ± 9.0 mm Hg to 8.8 ± 5.8 mm Hg (p = 0.016) and a decrease in LV end-diastolic volume from 172 ± 37 ml to 158 ± 38 ml (p < 0.001). None of the patients developed acute post-procedural low CO state. CONCLUSIONS Successful MV repair with the MitraClip system results in an immediate and significant improvement in FSV, CO, and LV loading conditions. There was no evidence of a low CO state following MitraClip treatment for MR. These favorable hemodynamic effects with the MitraClip appear to reduce the risk of developing a low CO state, a complication occasionally observed after surgical MV repair for severe MR.

Reproducibility of Proximal Isovelocity Surface Area, Vena Contracta, and Regurgitant Jet Area for Assessment of Mitral Regurgitation Severity

OBJECTIVES The aim of this study was to evaluate the interobserver agreement of proximal isovelocity surface area (PISA) and vena contracta (VC) for differentiating severe from nonsevere mitral regurgitation (MR). BACKGROUND Recommendation for MR evaluation stresses the importance of VC width and effective regurgitant orifice area by PISA measurements. Reliable and accurate assessment of MR is important for clinical decision making regarding corrective surgery. We hypothesize that color Doppler-based quantitative measurements for classifying MR as severe versus nonsevere may be particularly susceptible to interobserver agreement. METHODS The PISA and VC measurements of 16 patients with MR were interpreted by 18 echocardiologists from 11 academic institutions. In addition, we obtained quantitative assessment of MR based on color flow Doppler jet area. RESULTS The overall interobserver agreement for grading MR as severe or nonsevere using qualitative and quantitative parameters was similar and suboptimal: 0.32 (95% confidence interval [CI]: 0.1 to 0.52) for jet area-based MR grade, 0.28 (95% CI: 0.11 to 0.45) for VC measurements, and 0.37 (95% CI: 0.16 to 0.58) for PISA measurements. Significant univariate predictors of substantial interobserver agreement for: 1) jet area-based MR grade was functional etiology (p = 0.039); 2) VC was central MR (p = 0.013) and identifiable effective regurgitant orifice (p = 0.049); and 3) PISA was presence of a central MR jet (p = 0.003), fixed proximal flow convergence (p = 0.025), and functional etiology (p = 0.049). Significant multivariate predictors of raw interobserver agreement > or =80% included: 1) for VC, identifiable effective regurgitant orifice (p = 0.035); and 2) for PISA, central regurgitant jet (p = 0.02). CONCLUSIONS The VC and PISA measurements for distinction of severe versus nonsevere MR are only modestly reliable and associated with suboptimal interobserver agreement. The presence of an identifiable effective regurgitant orifice improves reproducibility of VC and a central regurgitant jet predicts substantial agreement among multiple observers of PISA assessment.

Aortic annular sizing for transcatheter aortic valve replacement using cross-sectional 3-dimensional transesophageal echocardiography.

OBJECTIVES This study compared cross-sectional three-dimensional (3D) transesophageal echocardiography (TEE) to two-dimensional (2D) TEE as methods for predicting aortic regurgitation after transcatheter aortic valve replacement (TAVR). BACKGROUND Data have shown that TAVR sizing using cross-sectional contrast computed tomography (CT) parameters is superior to 2D-TEE for the prediction of paravalvular aortic regurgitation (AR). Three-dimensional TEE can offer cross-sectional assessment of the aortic annulus but its role for TAVR sizing has been poorly elucidated. METHODS All patients had severe symptomatic aortic stenosis and were treated with balloon-expandable TAVR in a single center. Patients studied had both 2D-TEE and 3D imaging (contrast CT and/or 3D-TEE) of the aortic annulus at baseline. Receiver-operating characteristic curves were generated for each measurement parameter using post-TAVR paravalvular AR moderate or greater as the state variable. RESULTS For the 256 patients studied, paravalvular AR moderate or greater occurred in 26 of 256 (10.2%) of patients. Prospectively recorded 2D-TEE measurements had a low discriminatory value (area under the curve = 0.52, 95% confidence interval: 0.40 to 0.63, p = 0.75). Average cross-sectional diameter by CT offered a high degree of discrimination (area under the curve = 0.82, 95% confidence interval: 0.73 to 0.90, p < 0.0001) and mean cross-sectional diameter by 3D-TEE was of intermediate value (area under the curve = 0.68, 95% confidence interval: 0.54 to 0.81, p = 0.036). CONCLUSIONS Cross-sectional 3D echocardiographic sizing of the aortic annulus dimension offers discrimination of post-TAVR paravalvular AR that is significantly superior to that of 2D-TEE. Cross-sectional data should be sought from 3D-TEE if good CT data are unavailable for TAVR sizing.

A revised methodology for aortic-valvar complex calcium quantification for transcatheter aortic valve implantation

AIMS We sought to optimize a method for quantification of the calcium in the aortic-valvar complex for the prediction of significant paravalvular leak (PVL) after transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS All patients had severe symptomatic aortic stenosis and were treated with balloon-expandable TAVI (Sapien/Sapien-XT, Edwards Lifesciences LLC, Irvine, CA, USA). In order to correct for precise annular sizing, only patients with available contrast computed tomography (CT) data for measurements were included (n = 198). Paravalvular leak was quantified using peri-procedural transoesophageal echocardiography by Valve Academic Research Consortium-2 (VARC-2) criteria (grade ≥ moderate was considered significant). A detailed region-of-interest methodology separated quantification of calcium in each of the aortic leaflets to that in the left ventricular outflow tract (LVOT) and was used to predict PVL in receiver operator characteristic curve analyses. For non-contrast scans, the greatest discriminatory value for PVL was seen at the 450 Hounsfield Unit (HU) threshold for detection (volume ≥626 mm(3)), whereas for contrast scans it was at 850 HU (≥235 mm(3)). Left ventricular outflow tract calcium predicted PVL but only as a binary variable with no incremental value of quantification. In a multivariable binary logistic regression model, annulus area ≥ prosthesis area (OR 3.5, 95% CI 1.5-8.2, P = 0.005), contrast leaflet calcium volume (850-HU threshold) ≥235 mm(3) (OR 2.8, 95% CI 1.2-6.7, P = 0.023), and presence of LVOT calcium (OR 2.8, 95% CI 1.2-7.0, P = 0.022) were independent predictors for PVL ≥ moderate. CONCLUSION Both leaflet and LVOT calcium are significant predictors of PVL and exert an important synergistic influence on this complication, even in appropriately sized valves. With careful attention to thresholds for detection, clinically relevant leaflet calcium volumes can be identified with either non-contrast or contrast CT scans.

Value of Medical Therapy in Patients >80 Years of Age With Heart Failure and Preserved Ejection Fraction

Heart failure (HF) with preserved ejection fraction (EF) has a high prevalence in the geriatric population, and this cohort may be at risk of complications caused by polypharmacy. Effects of commonly used cardiac medications on long-term survival of patients >80 years with HF and preserved left ventricular EF were assessed. One hundred forty-two patients were evaluated. During a 5-year follow-up, 98 patients died (69%). There were no significant differences in baseline parameters in patients who died compared with those who survived at 5 years. None of the drug therapies appeared to make a significant difference in long-term survival, including beta blockers (p = 0.89), angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (p = 0.91), calcium channel blockers (p = 0.69), diuretics (p = 0.30), digoxin (p = 0.22), and statins (p = 0.32). In conclusion, based on the present data, it appears that use of certain common cardiac medications may not be associated with a significant effect on long-term survival in octogenarians with HF and preserved EF.

Acute effect of percutaneous MitraClip therapy in patients with haemodynamic decompensation

To evaluate the haemodynamic effect of acute procedural success (APS) after MitraClip therapy in patients with haemodynamic decompensation.

Value of Color Doppler Three-Dimensional Transesophageal Echocardiography in the Percutaneous Closure of Mitral Prosthesis Paravalvular Leak

We investigated the clinical value of three-dimensional (3D) transesophageal echocardiography (TEE) color flow Doppler (TEE-CFD) for percutaneous transcatheter closure of mitral valve prosthesis paravalvular leaks (PVLs) compared to two-dimensional (2D) TEE. The number, location, and size of the mitral valve prosthesis PVLs were determined in 8 patients using 2D and 3D TEE-CFD. We also evaluated 2D and 3D TEE-CFD for identifying the canalization of the target PVL during the intervention and assessing the change in the PVL effective orifice after the endovascular procedure. We visualized 12 PVLs using 2D TEE-CFD and 15 PVLs using 3D TEE-CFD. No substantial disagreement was found between 2D and 3D TEE-CFD for the location for each of the PVLs. No difference was found in the vena contracta short axis width obtained by 2D TEE-CFD and 3D TEE-CFD (5.7 +/- 1.4 mm vs 5.5 +/- 1.3 mm, respectively, p = 0.09). However, only 3D TEE-CFD demonstrated the effective circumferential orifice length of the PVL (12.2 +/- 8.5 mm). A closure device was deployed in 6 cases. In 1 case, the canalization of a nontarget PVL, visualized only on 3D TEE-CFD, led to an appropriate change in the treatment strategy. The reduction in the mean PVL vena contracta width demonstrated using 2D TEE-CFD and 3D TEE-CFD was similar (2.2 +/- 0.7 mm vs 2.1 +/- 1.1 mm, respectively, p = 0.69). However, only 3D TEE-CFD verified the reduction of the effective orifice circumferential length of the PVL by 10.5 +/- 5.6 mm. In conclusion, 3D TEE-CFD provided unique and additive information in patients with mitral valve prosthesis PVLs. This new technology has the potential to improve the procedural success of percutaneous transcatheter closure of PVLs.

Predictors of depressive symptoms post-acute coronary syndrome

OBJECTIVE We examined the influence of gender on the prevalence of acute coronary syndrome (ACS) and the severity of depressive symptoms post-ACS. METHODS Patients received a Zung self-assessment questionnaire at hospital discharge for unstable angina (UA) or acute myocardial infarction (AMI) and returned it by mail. Major depressive symptoms were diagnosed based on a summed depressive symptoms (SDS) score of >50. Depressive symptomatology was modeled by stepwise multivariable logistic regression with the following predictors: gender, age, hypertension, diabetes mellitus, history of smoking, hypercholesterolemia, peripheral vascular disease, prior stroke, prior myocardial infarction (MI), and prior percutaneous coronary intervention or coronary artery bypass graft surgery. We also modeled severity of depressive symptoms via stepwise multiple linear regression with the same predictor variables. RESULTS A total of 944 patients were surveyed: 716 men and 228 women, mean (SD) age, 67 (13) years and 71 (12) years, respectively. Of these patients, 250 (35%) men and 103 (45%) women had depressive symptoms (P = 0.005). No significant difference was observed between men and women in rates of cardiac catheterization; severity of coronary artery disease; treatment with antiplatelet agents, beta-blockers, angiotensin-converting enzyme inhibitors, or statins; or percutaneous or surgical revascularization rates during or post-ACS. Significant predictors of the presence of depressive symptoms were female gender (odds ratio [OR] = 1.64; 95% CI, 1.19-1.28), diabetes mellitus (OR = 1.42; 95% CI, 1.03-1.97), prior MI (OR = 1.56; 95% CI, 1.15-2.20), and smoking (OR = 1.41; 95% CI, 1.01-1.97). Variables significantly associated with a higher severity of depressive symptoms were female gender, prior MI, smoking, and stroke. Men with prior MI had significantly higher mean (SD) SDS scores than did men without prior MI in all age groups (48.4 [11] vs 44.6 [11], respectively; P < 0.001). In addition, significantly more men with prior MI had depressive symptoms compared with those without prior MI (45% vs 32%; P = 0.001). However, prior MI did not appear to affect SDS scores in women (49.1 [12] for prior MI vs 48.5 [12] for no prior MI; P = NS), and there was no significant difference in the percentage of women who had depressive symptoms with or without a history of prior MI. Depressive symptoms were much more severe in women with UA (SDS = 49.0 [12]) compared with women with AMI (SDS = 45.0 [12]; P = NS), or men with AMI (45.0 [12]; P = 0.004) or UA (46.0 [11]; P = 0.007) (analysis of variance, P = 0.003). CONCLUSIONS Female gender is a significant independent predictor of depressive symptoms and their severity post-UA and post-AMI. History of prior MI is associated with a higher frequency and severity of depressive symptoms in men. These findings call for routine screening for depressive symptoms in men with prior MI and in women who present with ACS.

Heart-rate adjustment of transcatheter haemodynamics improves the prognostic evaluation of paravalvular regurgitation after transcatheter aortic valve implantation.

AIMS Paravalvular aortic regurgitation (PVAR) after balloon-expandable transcatheter aortic valve implantation (TAVI) remains difficult to quantify, and the utility of the AR index (ARi) to create a composite aortic insufficiency (CAI) score was an important advance. Heart rate (HR) influences the ARi but the clinical relevance of this phenomenon remains poorly appreciated. We sought to validate a new composite heart-rate-adjusted haemodynamic-echocardiographic aortic insufficiency (CHAI) score in the prognostic evaluation of PVAR after balloon-expandable TAVI. METHODS AND RESULTS The severity of PVAR was assessed immediately post TAVI by transoesophageal echocardiography (TOE) with simultaneous assessment of transcatheter haemodynamics. A total of 303 patients were studied. The CHAI score, incorporating the HR-adjusted diastolic-delta (HRA-DD, the difference between left ventricular and aortic diastolic pressures/HR*80), had a greater discriminatory value for one-year mortality than both PVAR by TOE (p=0.0018) and the previously proposed CAI score, based on the ARi without HR adjustment (p=0.0029). The CHAI score also better stratified percentage increases in left ventricular systolic chamber dimensions at one month and serum natriuretic peptide levels at one to three months. CONCLUSIONS Prognostication of PVAR in the intermediate range of echocardiographic severity remains unreliable and is greatly enhanced by the integration of heart-rate-adjusted transcatheter haemodynamics.