Julie Melchior

Prognostic Significance of LGE by CMR in Aortic Stenosis Patients Undergoing Valve Replacement

BACKGROUND Prior studies have shown that late gadolinium enhancement (LGE) by cardiac magnetic resonance (CMR) can detect focal fibrosis in aortic stenosis (AS), suggesting that it might predict higher mortality risk. OBJECTIVES This study was conducted to evaluate whether LGE-CMR can predict post-operative survival in patients with severe AS undergoing aortic valve replacement (AVR). METHODS We prospectively evaluated survival (all-cause and cardiovascular disease related) according to LGE-CMR status in 154 consecutive AS patients (96 men; mean age: 74 ± 6 years) without a history of myocardial infarction undergoing surgical AVR and in 40 AS patients undergoing transcatheter aortic valve replacement (TAVR). RESULTS LGE was present in 29% of patients undergoing surgical AVR and in 50% undergoing TAVR. During a median follow-up of 2.9 years, 21 patients undergoing surgical AVR and 20 undergoing TAVR died. In surgical AVR, the presence of LGE predicted higher post-operative mortality (odds ratio: 10.9; 95% confidence interval [CI]: 1.2 to 100.0; p = 0.02) and worse all-cause survival (73% vs. 88%; p = 0.02 by log-rank test) and cardiovascular disease related survival (85% vs. 95%; p = 0.03 by log-rank test) on 5-year Kaplan-Meier estimates of survival after surgical AVR. Multivariate Cox analysis identified the presence of LGE (hazard ratio: 2.8; 95% CI: 1.3 to 6.9; p = 0.025) and New York Heart Association functional class III/IV (hazard ratio: 3.2; 95% CI: 1.1 to 8.1; p < 0.01) as the sole independent predictors of all-cause mortality after surgical AVR. The presence of LGE also predicted higher all-cause mortality (p = 0.05) and cardiovascular disease related mortality (p = 0.03) in the subgroup of patients without angiographic coronary artery disease (n = 110) and higher cardiovascular disease related mortality in 25 patients undergoing transfemoral TAVR. CONCLUSIONS The presence of LGE indicating focal fibrosis or unrecognized infarct by CMR is an independent predictor of mortality in patients with AS undergoing AVR and could provide additional information in the pre-operative evaluation of risk in these patients.

Natural History of Paradoxical Low-Gradient Severe Aortic Stenosis

Background—Up to 30% of patients with severe aortic stenosis (SAS; indexed aortic valve area <0.6 cm2/m2) present with low transvalvular gradient despite a normal left ventricular ejection fraction. Presently, there is intense controversy as to the prognostic implications of such findings. Accordingly, the aim of the present work was to compare the natural history of patients with paradoxical low-gradient (PLG) or high-gradient (HG) SAS. Methods and Results—We prospectively studied 349 patients with SAS and preserved left ventricular ejection fraction. Patients were categorized into HG-SAS (n=144) and PLG-SAS (n=205) according to mean transvalvular gradient (mean gradient >40 or ⩽40 mm Hg). Primary end points were all-cause mortality and echocardiographic disease progression. To evaluate natural history, patients undergoing aortic valve replacement were censored at the time of surgery (n=92). During a median follow-up of 28 months, 148 patients died. Kaplan–Meier survival curves showed better survival in PLG-SAS than in HG-SAS, both in the overall population (48% versus 31%; P<0.01) and in the asymptomatic subgroup (59% versus 35%; P<0.02). In asymptomatic patients, Cox analysis identified age, diabetes mellitus, left atrial volume, and mean gradient as independent predictors of death. Finally, at last echocardiographic follow-up, PLG-SAS demonstrated significant increases in mean gradient (from 29±6 to 38±11 mm Hg; P<0.001). Conclusions—Our study indicates that PLG-SAS is a less malignant form of AS compared with HG-SAS, because their spontaneous outcome is better. We further demonstrated that patients with PLG-SAS are en route toward the more severe HG-SAS form, because the majority of them evolve into HG-SAS over time.

Aortic Valve Area, Stroke Volume, Left Ventricular Hypertrophy, Remodeling, and Fibrosis in Aortic Stenosis Assessed by Cardiac Magnetic Resonance Imaging Comparison Between High and Low Gradient and Normal and Low Flow Aortic Stenosis

Background—Recent works using echocardiography suggested that low gradient (LG), low flow (LF) aortic stenosis (AS) has more pronounced left ventricular (LV) concentric remodeling, smaller LV cavity size, and more interstitial fibrosis compared with high gradient (HG) normal flow (NF) AS. Therefore, we evaluated the accuracy of echocardiographic measurements and compared remodeling and fibrosis in different types of AS by cardiac magnetic resonance (CMR). Methods and Results—A total of 128 patients (73±11 years of age; 75 men) with aortic valve area (AVA) <0.6 cm2/m2 and ejection fraction >50% by echocardiography underwent CMR to measure planimetric AVA, phase-contrast indexed stroke volume, LV mass, and focal fibrosis. Using <40 mm Hg and indexed stroke volume <35 mL/m2 by echocardiography as criteria for LG and LF, 69 (54%) patients were HG/NF, 28 (22%) HG/LF, 17 (13%) LG/NF, and 14 (11%) LG/LF AS. LV outflow tract area, indexed stroke volume, and AVA correlated well between echocardiography and CMR (r=0.7, 0.61, and 0.65, respectively; P<0.001 for all). By CMR, however, planimetric AVA was larger in LF/LG (0.54±0.08 cm2/m2) and LG/NF (0.61±0.08 cm2/m2) than in HG/LF (0.46±0.07 cm2/m2; P<0.05) AS, and indexed LV mass was lower in LG/LF (75±12 g/m2) and LG/NF (81±18 g/m2) than in HG/LF (100±27 g/m2; P<0.05) AS. All groups of AS had similar LV volumes, predominantly concentric hypertrophy remodeling, and similar amounts of focal fibrosis. Conclusions—CMR confirmed overall accuracy of echocardiographic classification of AS but demonstrated that LG/LF and LG/NF AS have larger AVA, less LV hypertrophy, and similar focal fibrosis compared with HG/LF AS. This challenges the view that LG/LF AS is a more advanced state of AS.

Stentless xenografts as an alternative to pulmonary homografts in the Ross operation

OBJECTIVES Because of the limited availability of pulmonary homografts (PH), porcine stentless xenografts (SX) have been proposed as an alternative for pulmonary valve replacement in the Ross operation. However, it is unknown whether they have similar good long-term durability. Therefore, we compared mid- to long-term outcomes between those two right ventricular outflow tract (RVOT) substitutes. METHODS In 288 adults (>18 years) undergoing a Ross operation between 1991 and 2012, Freestyle(®) SX was used in 18 patients and a cryopreserved PH was used in 270 for RVOT reconstruction. Only patients with follow-up >2 years were included. According to the operative period, gender and age, 37 patients with PH could be matched with 17 SX patients. Clinical and echocardiographic follow-up were obtained. In a subset of patients (SX, n = 11 and PH, n = 25), a cardiac computed tomographic (CT) scan was performed to analyse graft calcification. RESULTS The mean follow-up period was 8.2 ± 4.0 (range 2-14.6 years). During this period, 3 patients died from cancer, 2 in the SX group and 1 in the PH group (P = 0.15). No patient needed RVOT reoperation. At follow-up, RVOT peak gradient was 21 ± 5.9 mmHg in the SX and 16.3 ± 8.7 in the PH groups (P = 0.07). Peak gradient >40 mmHg was observed in only 1 patient in the PH group. Mean RVOT regurgitation was 0.1 ± 0.4 in the SX group and 0.8 ± 0.6 in the PH group (P = 0.008). CT scan analyses showed progressive calcification mainly of the graft wall, while the valve remained relatively free of calcium. Patients with the SX presented significantly higher calcium scores than those with PH (P = 0.01). CONCLUSIONS In adult patients having the Ross operation, calcic degeneration is observed in both the PH and the SX used as pulmonary substitutes. Calcification progresses more rapidly in the SX compared with the PH. In both grafts, calcifications affect mainly the wall, while the valve remains relatively free of calcium. As a consequence, both grafts show good and similar haemodynamic outcomes at mid- to long-term follow-up. The Freestyle(®) SX can be considered as an acceptable alternative for RVOT reconstruction when PH is not available.

The role of echocardiography in aortic valve repair

Echocardiography is the imaging method of choice for evaluating aortic valve repair for aortic regurgitation (AR). This article will discuss the role of echocardiography in the assessment of the severity, hemodynamics and mechanism(s) of AR, along with its role in the perioperative assessment of aortic valve repair.

0294: Extravascular volume by cardiac MR T1 mapping accurately predicts histologically measured fibrosis in valve disease

Background Valvular heart disease is associated with left ventricular hypertrophy, remodeling and development of diffuse interstitial fibrosis. So far, histopathology remains the gold standard for evaluating diffuse myocardial fibrosis. Gadolinium enhanced Cardiac Magnetic Resonance (CMR) T1 mapping is new method which allows to quantify the myocardial extracellular volume (ECV). Hence, it was suggested that this ECV measurements allows to non-invasive estimate diffuse fibrosis. However validations studies are scars. Therefore the aim of this study was to validate measurements of ECV by T1-Modified Lock-locker (MOLLI) CMR against histological measurement. Methods and results Between June 2012 and September 2013, 15 patients (age=57±15 years, 73% men) with either severe aortic valve disease (stenosis or regurgitation) or severe mitral regurgitation, but without coronary artery disease preoperatively underwent ECV measurement by CMR MOLLI T1 mapping. LV biopsies were performed at the time of surgery 7±8 days later and stained with Sirius red. The amount of fibrosis quantified by biopsy was 6.6±4.8% [2.1;15.9]. ECV by T1 mapping was 28.3±4.7% [23.3;38.6] (values are presented as mean±SD [min;max]). There was a good correlation between histologically measured fibrosis and T1 mapping ECV (r=0.77, p Conclusion ECV determined by CMR T1 mapping closely correlates with histologically determined diffuse interstitial fibrosis and could thus be used to non-invasively quantify interstitial fibrosis in patients with heart diseases.

Relative contribution of afterload and interstitial tissue fibrosis to preoperative longitudinal function in patients with severe aortic stenosis: implications for postoperative functional recovery

Background: Several previous studies have demonstrated that, in patients with severe aortic stenosis (SAS), chronic pressure overload hypertrophy frequently results in reduced longitudinal function as assessed by tissue Doppler or speckle tracking echocardiography (STE). The aim of the present study was to determine the relative contribution of structural (interstitial fibrosis) and functional (afterload) alterations in this process and to evaluate the implications thereof for functional recovery after aortic valve replacement (AVR). Methods: 34 patients with isolated SAS underwent pre-operative resting conventional echocardiography and STE, to calculate end-systolic wall stress (ESS) and to measure global longitudinal strain (GLS) and left ventricular ejection fraction (LVEF). At the time of AVR, a per-operative transmural biopsy was obtained in every patient, to quantify the degree of interstitial fibrosis. Echocardiographic functional parameters were reassessed 6 months after AVR. Results: Compared to age-matched normal controls, SAS patients exhibited significantly reduced GLS (-12.5 ± 3.9% vs -18.2 ± 1.5% p<0.0001) and LVEF (57 ± 13 vs 66 ± 4%, p=0.026). With univariate analysis, pre-operative GLS was found to correlate significantly with LVEF (r=0.70, p<0.0001), interstitial fibrosis (r=-0.60, p=0.0002), LV mass (r=-0.52, p=0.002) and ESS (r=-0.61, p=0.0001). Using stepwise multiple regression analysis, only the degree of interstitial fibrosis and ESS were found to be independent correlates of pre-operative GLS (r=0.74). Interestingly,unstressed pre-operative GLS, extrapolated as GLS at zero stress, correlated well with interstitial fibrosis (r=0.51) and predicted GLS at the 6-months post-operative follow-up (r=0.55). Conclusions: In patients with SAS, reduced longitudinal function results from both excessive afterload and structural tissue alterations (interstitial fibrosis). Unstressed pre-operative GLS was found to be a reasonable correlate of tissue fibrosis and to allow prediction of long term post-operative longitudinal function.

Natural History Of Severe Aortic Stenosis With Preserved Ejection Fraction: Impact Of Transvalvular Gradients and Flow

Background: Recent studies have indicated that up to 30% of patients (pts) with severe aortic stenosis (SAS), defined as an indexed aortic valve area 40 mmHg) and indexed stroke volume (≤ ou > 35 ml/m2). The primary endpoint was all causes mortality. To evaluate natural history, pts undergoing surgery during follow–up were censored at the time of surgery (n=84). Results: 145 had HG SAS (45%) and 215 had LG SAS (55%). During a mean follow–up of 36 ± 28 months, 154 patients died. Cox analysis identified age, NYHA class, the presence of diabetes and chronic obstructive lung disease as independant predictor of death. In the subgroup of asymptomatic pts, the same analysis identified age, the presence of diabetes and mean transvalvular gradient as independent predictors of death. Kaplan Meier survival curves demonstrated that survival was better in pts with LG SAS than in those with HG SAS, both in the overall population (47 vs 31%, p<0.01) and in the asymptomatic subgroup (58 vs 35%, p<0.03). By contrast, indexed stoke volume did not influence outcome. Conclusions: In pts with SAS and normal LVEF, those with LG SAS have a better prognosis that those with HG SAS. Indexed stroke volume does not influence outcome.