Morphological and dynamic analysis of the normal aortic valve with 4D computed tomography.

OBJECTIVES: To evaluate the precise dimensions of the normal aortic root, especially the true aortic annulus, during the cardiac cycle using an innovative reconstruction method based on multiphase cardiac computed tomography and to assess the feasibility and the reproducibility of this method for aortic root analysis. METHODS: Between January 2019 and June 2021, 30 optimal consecutive ECG-gated multiphase cardiac computed tomography of patients with normal tricuspid aortic valve were analysed using an in-house software. Aortic annulus border was pinpointed on 9 reconstructed planes and the 3D coordinates of the 18 consecutive points were interpolated into a 3D curve using a cubic spline. Three additional planes were generated at the level of the left ventricular outflow tract, the level of the Valsalva sinus and the level of the sinotubular junction. This procedure was repeated for all the 10 temporal phases of the RR interval. RESULTS: The aortic annulus mean 3D and 2D areas were 7.67 ± 1.51 and 5.16 ± 1.40 cm2, respectively. The mean 2D diameter was 2.51 ± 0.23 cm. The mean global area expansion was 11.8 ± 3.5% and the mean perimeter expansion of 7.1 ± 2.6%. During the cardiac cycle, the left ventricle outflow tract expands, reaching its maximum surface at the end of diastole, followed by the aortic annulus, the Valsalva sinuses and the sinotubular junction. The aorta changes from a clover-shaped cone during diastole to more cylindrical shape during systole. Compared to the 3D measurements, the analysis of the virtual basal ring significantly underestimates the annulus area, perimeter, and mean diameter. CONCLUSIONS: 4D morphometric analysis enables to have a precise and reproducible evaluation of the aortic annulus. The aortic annulus and root are deformable structures that undergo a unique expansion sequence during the cardiac cycle which should be considered for procedural planning.

Distribution and determinants of coronary artery calcium score in asymptomatic patients with Type-2 diabetes: The French-CAC100 score.

BACKGROUND: Coronary artery calcium score (CACS) refines the cardiovascular disease (CVD) risk prediction in patients with Type-2 diabetes (T2D). We aimed to identify the determinants for high CACS in CVD-free patients with T2D. METHODS: We studied 796 patients with T2D with CACS measured in three centers: two in continental France and a third in the Reunion Island. To predict a CACS ≥ 100, we derived a risk score in patients in continental France, and validated it in those in the Reunion Island. RESULTS: The distributions of CACS distributions were similar among patients in continental France and Reunion Island. The French-CAC100 score included 5 parameters (age, sex, diabetes duration, non-CV end-organ damage and presence of ≥ 2 other CVD risk factors), ranging from 0 to 22 points. Similar areas under the curves were found for the risk score in both settings (0.80 vs. 0.73, p = 0.10). A French-CAC100 score < 10 excluded the odds for CACS ≥ 100 and CACS ≥ 400 with negative predictive values of 90% and 97% respectively, avoiding 58% of CT-scans. CONCLUSION: Regardless of the geographic area, patients with T2D share similar risk factors for high CACS. The French-CAC100 score allows the identification of those at higher risk of elevated CACS.

Left ventricular assessment in patients with systemic light chain amyloidosis: a 3-dimensional speckle tracking transthoracic echocardiographic study.

Cardiac involvement in systemic light chain (AL) amyloidosis carries a poor prognosis mainly through involvement of the left ventricular (LV) myocardium. Despite its limitations, two-dimensional transthoracic echocardiography (2D-TTE) remains the main tool used for the assessment of LV systolic function in AL patients. We hypothesize that 3D-TTE coupled with speckle tracking imaging allows earlier detection of LV systolic dysfunction than 2D-TTE in AL amyloidosis. We prospectively studied 71 subjects including 58 patients with confirmed AL amyloidosis (mean age 66 ± 10 years, 60% male) and 21 healthy control (mean age 64 ± 7 years, 48% male) from 2011 to 2014 at the University Hospital of Limoges. The AL patients were divided into three groups according to Mayo Clinic (MC) staging and all subjects underwent 2D-TTE and 3D-TTE at the same setting. Using 2D-TTE, there was no significant difference in LV ejection fraction (EF) between the groups [LVEF = 63 ± 7% (control), 59 ± 6% (MC stage I), 60 ± 8% (MC stage II) and 57 ± 14% (MC stage III) (p = 0.24)]. In contrast, 3D-TTE demonstrated significantly worse LV systolic function in stage II and III patients using 3D-LVEF [MC II and III 45 ± 8% and 39 ± 12% vs. control 53 ± 8% (p < 0.0001)], global longitudinal strain (GLS) [MC II and III - 11 ± 4% and - 8 ± 3% vs. control - 15 ± 3% (p < 0.0001)] and global radial strain (GRS) [MC II and III 14 ± 9% and 10 ± 8% vs. control 25 ± 10% (p < 0.0001)]. Furthermore, MC III patients had significantly worse global circumferential strain and area tracking [- 17 ± 6% and - 25 ± 8% vs. - 24 ± 7% and - 36 ± 7% for control (p < 0.0001)]. Additionally, MC I had significantly better 3D GLS, GRS and global strain (- 15 ± 3%, 25 ± 10% and 28 ± 12%) than MC II (- 11 ± 4%, 14 ± 9% and 16 ± 10%) and MC III patients (- 8 ± 3%, 10 ± 8% and 12 ± 8%), respectively. Despite an apparently preserved LVEF by 2D-TTE, AL patients in MC stage II and III demonstrate evidence of LV systolic dysfunction by 3D imaging using LVEF and strain analysis. Worse LV involvement by AL amyloidosis was associated with more impaired 3D-TTE LV systolic parameters.

Comparison of echocardiographic parameters in Fabry cardiomyopathy and light-chain cardiac amyloidosis.

BACKGROUND: Fabry cardiomyopathy (FC) and light-chain amyloid cardiomyopathy (AL) present with concentric left ventricular (LV) hypertrophy/remodeling and diastolic rather than systolic dysfunction. Direct comparisons are difficult due to rarity and confounded by variability of LV thickness. AIMS: To compare LV diastolic and systolic properties between patients with FC and AL in a cohort matched for interventricular septal thickness (IVS). METHODS: A two-center echocardiographic analysis was performed, comprising 118 patients with IVS ≥12 mm (FC and AL 59 patients each) matched by IVS. RESULTS: Fabry cardiomyopathy patients had larger LV end-diastolic diameter (47.7 [44.0-50.9] vs 45.0 [41.5-49.0] mm, P = 0.002), better LV ejection fraction (EF 68.7 [63.4-74.0] vs 63.0 [54.0-70.0]%, P = 0.001) and midwall fractional shortening (midFS 14.8 [13.0-16.1] vs 12.1 [8.9-15.0]%, P = 0.006). LV EF <40% was rare in both (2% vs 7%, P = 0.17). AL patients expressed higher LV diastolic dysfunction grade (III in 26% vs 4%, II in 21% vs 12% and I in 54% vs 84%, P = 0.004), with higher E/e' ratio (13.6 [10.2-18.8] vs 9.8 [7.5-12.3], P < 0.0001). Average E/e' ratio and midFS were significantly associated with NYHA severity in both groups (P < 0.05 for all). CONCLUSIONS: Matched AL patients had worse LV diastolic function than FC, driven by E/e'. Significant LV systolic dysfunction was rare overall. MidFS and E/e' were associated with heart failure severity in both groups.

Left atrial function in patients with light chain amyloidosis: A transthoracic 3D speckle tracking imaging study.

BACKGROUND: Systemic light chain amyloidosis (AL) is characterized by the extracellular deposition of amyloid fibrils. Transthoracic echocardiography is the modality of choice to assess cardiac function in patients with AL. Whereas left ventricular (LV) function has been well studied in this patient population, data regarding the value of left atrial (LA) function in AL patients are lacking. In this study, we aim to examine the impact of LA volumes and function on survival in AL patients as assessed by real-time 3D echocardiography. METHODS: A total of 77 patients (67±10 years, 60% men) with confirmed AL and 39 healthy controls were included. All standard 2D echocardiographic and 3D-LA parameters were obtained. RESULTS: Fourteen patients (18%) were in Mayo Clinic (MC) stage I, 30 (39%) in stage II, and 33 (43%) in stage III at initial evaluation. There was no significant difference among the MC stages groups in terms of age, gender, or cardiovascular risk factors. As compared to patients in MC II and MC I, those in MC III had significantly larger indexed 3D-LA volumes (MCIII: 46±15mL/m2, MC II: 38±12mL/m2, and MC I: 23±9mL/m2, p<0.0001), lower 3D-LA total emptying fraction (3D-tLAEF) (21±13% vs. 31±15% vs. 43±7%, respectively, p<0.0001), and worse 3D peak atrial longitudinal strain (3D-PALS) (11±9% vs. 18±13% vs. 20±7%, respectively, p=0.007). Two-year survival was significantly lower in patients with 3D-tLAEF <+34% (p=0.003) and in those with 3D-PALS <+14% (p=0.034). Both parameters provided incremental prognostic value over maximal LA volume in multivariate analysis. CONCLUSION: Functional LA parameters are progressively altered in AL patients according to the MC stage. A decrease in 3D-PALS is associated with worse outcome, independently of LA volume.

Impact of Pulmonary Hypertension on Outcome in Patients with Severe Aortic Stenosis and Preserved Left Ventricular Ejection Fraction.

AIMS: The prognostic impact of elevated pulmonary arterial pressure (PAP) remains controversial in aortic stenosis (AS) and few studies focused on patients with preserved left ventricular ejection fraction (LVEF). We aimed to investigate the impact of pulmonary hypertension (PH), invasively derived, on survival in severe AS with preserved LVEF. METHODS AND RESULTS: Between 2000 and 2010, 749 patients (74 ± 8 years, 57% males) with preserved LVEF and severe AS without other valvular heart disease underwent cardiac catheterization. PH was defined as mean PAP > 25 mmHg. The mean follow-up was 4.6 ± 3.0 years. Overall, 32% (n = 241) of patients had PH. Surgical aortic valve replacement (SAVR) was performed in 91% of patients with 4.5% of 30-day mortality rate, significantly higher in patients with PH than without PH (7.5 vs. 3.5%, p = 0.014). In logistic regression, PH was an independent predictor of increased 30-day mortality (odds-ratio = 2.2, p = 0.04). Overall long-term survival was significantly reduced in patients with PH as compared to those without (10-year: 52 ± 5 vs. 68 ± 3%, p < 0.0001). Likewise, focusing on patients with SAVR showed significant reduced survival in those with PH (10-year: 57 ± 5 vs. 72 ± 3%, p < 0.0001). In multivariate analysis, after adjustment for relevant cofactors, PH was an independent predictor of mortality (hazard ratio = 1.5, p = 0.009). Using quartiles of mean PAP, only patients with most elevated values (Q4: mean PAP: 27-67mmHg) had significantly reduced survival, as compared to other quartiles (all p < 0.0001). CONCLUSION: In patients with severe AS and preserved LVEF, PH is an independent predictor of 30-day and long-term mortality patients. Nevertheless, only severely elevated PAP seems associated with reduced survival.

Prevalence and prognostic impact of left-sided valve thickening in systemic light-chain amyloidosis.

BACKGROUND: Left heart valve thickening (LVT) was described in patients with light-chain amyloidosis (AL). This phenomenon reflects likely infiltration of the valve by amyloid proteins. However, the prevalence of LVT and its prognostic value have not been investigated in patients with AL. METHODS AND RESULTS: Comprehensive transthoracic echocardiography was performed at baseline in 150 patients [median age 68 (33-87) years; 59% male] with confirmed AL. The presence of abnormal mitral and/or aortic valve thickening (>3 mm) was assessed in all included patients. Overall, 42% had LVT at the time of diagnosis. Compared to patients without LVT, those with LVT were older and had a more advanced NYHA functional class (63% in patients with NYHA III-IV vs. 33% in NYHA I-II, p < 0.001). They also had higher left ventricular (LV) wall thickness and mass, larger left atrium, higher mitral annulus E/E' ratio and systolic pulmonary artery pressures, and lower LV ejection fraction (all p < 0.05). Patients with more advanced Mayo Clinic stage had a higher incidence of LVT: 58% in stage III vs. 45% in stage II and 5% in stage I (p < 0.001). During a median follow-up of 2 years, 79 deaths occurred. The presence of LVT was significantly associated with reduced 5-year survival (32 ± 7 vs. 64 ± 6%). In multivariate analysis, after adjusting for age, gender, NYHA functional class, and LV ejection fraction, LVT remained significantly associated with higher all-cause mortality (hazard ratio 1.90, 95% CI 1.10-3.34, p = 0.02). CONCLUSION: Left heart valve thickening is common in patients with AL and is associated with worse functional class, LV systolic and diastolic function, and more advanced stage of the disease. In addition, LVT appears to be a powerful marker of all-cause mortality.

Prognostic value of left atrial function in systemic light-chain amyloidosis: a cardiac magnetic resonance study.

BACKGROUND: Cardiac involvement in systemic light-chain amyloidosis (AL) imparts an adverse impact on outcome. The left atrium (LA), by virtue of its anatomical location and muscular wall, is commonly affected by the amyloid process. Although LA infiltration by amyloid fibrils leads to a reduction in its pump function, the infiltration of the left ventricular (LV) myocardium results in diastolic dysfunction with subsequent increase in filling pressures and LA enlargement. Even though left atrial volume (LAV) is an independent prognostic marker in many cardiomyopathies, its value in amyloid heart disease remains to be determined. In addition, few data are available as to the prognostic value of LA function in systemic AL. Using cardiac magnetic resonance (CMR), the current study aims to assess the prognostic significance of the maximal LAV and total LA emptying fraction (LAEF) in patients with AL. METHODS AND RESULTS: Fifty-four consecutive patients (age 66 ± 10 years, 59% males) with confirmed systemic AL and mean LV ejection fraction of 60 ± 12% underwent CMR. As compared with patients with no or minimal cardiac involvement (Mayo Clinic [MC] stage I), those at moderate and high risk (MC stages II and III) had significantly larger indexed maximal LAV (36 ± 15 vs. 46 ± 13 vs. 52 ± 19 mL/m(2), P = 0.03) and indexed minimal LAV (20 ± 6 vs. 34 ± 11 vs. 44 ± 17 mL/m(2), P < 0.001), lower LAEF (42 ± 9 vs. 26 ± 13 vs. 16 ± 9%, P < 0.0001) but similar LVEF. Furthermore, myocardial late gadolinium enhancement (LGE) was more frequent and significantly associated with lower LAEF. LAEF was also significantly lower in symptomatic (NHYA ≥ II, 22 ± 14%) as compared with asymptomatic patients (NYHA class I, 33 ± 13%, P = 0.006). Two-year survival rate was lower in patients with LAEF ≤ 16% as compared with those with LAEF > 16% (37 ± 11 vs. 94 ± 4%, P = 0.001). In multivariate analysis, lower LAEF remained independently associated with a higher risk of 2-year mortality (HR = 1.08 per 1% decrease, 95% CI: 1.02-1.15, P = 0.003). CONCLUSION: In patients with systemic AL, LAEF as assessed by CMR is associated with NYHA functional class, MC stage, myocardial LGE and 2-year mortality.

Prognosis importance of low flow in aortic stenosis with preserved LVEF.

AIMS: Previous studies using echocardiography suggested that a low flow (LF) defined as an indexed stroke volume (SVi) <35 mL/m(2) may be an important determinant of outcome in patients with severe aortic stenosis (AS). We sought to assess the prognostic importance of stroke volume derived from invasive data. The aim of this study was to determine the impact of LF, purposely derived from cardiac catheterisation data, on outcome of patients with severe AS and preserved LVEF. METHODS: Between 2000 and 2010, 768 patients with preserved LVEF (>50%) and severe AS (valve area ≤1 cm(2)) without other valvular heart disease underwent cardiac catheterisation. The long-term overall mortality was assessed as the primary end-point. RESULTS: Mean age was 74±8 years, 58% were men, 46% had coronary artery disease and mean LVEF was 72±10%. Low SVi was found in 27% (n=210) of patients with AS. As compared with patients with normal SVi, those with low SVi were significantly older (p<0.0001) with higher rate of atrial fibrillation (p<0.0001). Additionally, they had lower LVEF (p=0.046), aortic valve area (p<0.0001), mean pressure gradient (p<0.0001), systemic arterial compliance (p<0.0001) and higher systemic vascular resistances (p<0.0001). Eight-year survival was significantly reduced in patients with low SVi as compared with those with normal SVi (51±5% vs 67±3%; p<0.0001). After adjustment for all other risk factors, reduced SVi was independently associated with long-term mortality (HR=1.45, 95% CI 1.1 to 2.1; p=0.048). CONCLUSIONS: In patients with severe AS and preserved LVEF, LF, as assessed using cardiac catheterisation is frequent, and is an independent predictor of mortality. Consequently, the measurement of SVi should be systematically included in the assessment of these patients.

Prognostic impact of global left ventricular hemodynamic afterload in severe aortic stenosis with preserved ejection fraction.

INTRODUCTION: Global left ventricular (LV) afterload as assessed by valvulo-arterial impedance (Zva), may be an independent predictor of mortality in patients with severe aortic stenosis (AS) and preserved LV ejection fraction (LVEF). However, its quantification using echocardiography may be subject to error measurement. We aimed to determine the prevalence and impact on long-term survival of high Zva, purposely measured by cardiac catheterization. METHODS AND RESULTS: 676 patients with preserved LVEF and severe AS without other valvular heart diseases underwent cardiac catheterization. Zva was derived from catheterization and calculated as follows: mean aortic gradient+systolic blood pressure/indexed LV stroke volume. Zva was considered high when >5mmHg/mL/m(2) based on previous studies. Overall, high Zva was found in 42% of all AS patients. Four-year survival and 8-year survival were significantly reduced in patients with high Zva (74±3% and 57±4%) as compared to those with low Zva (85±2% and 74±3%; p=0.002). After adjustment for all other risk factors, Zva was independently associated with reduced long-term survival (hazard ratio [HR]=1.47 95% CI: 1.04-2.09; p=0.029). Of interest, high Zva remained associated with reduced survival as compared to low Zva, in patients with normal LV stroke volume, but was no longer significant in low flow patients (p=0.98). CONCLUSION: High Zva, estimated invasively in our study, is frequent in patients with severe AS, and appears as a robust and independent predictor of survival. Zva should be used as an additional parameter for risk stratification of severe AS, more particularly in patients with normal flow.

Prevalence and long-term outcome of aortic prosthesis-patient mismatch in patients with paradoxical low-flow severe aortic stenosis.

BACKGROUND: Patients with severe aortic stenosis (AS) and paradoxical low flow (PLF) have worse outcome compared with those with normal flow. Furthermore, prosthesis-patient mismatch (PPM) after aortic valve replacement is a predictor of reduced survival. However, the prevalence and prognostic impact of PPM in patients with PLF-AS are unknown. We aimed to analyze the prevalence and long-term survival of PPM in patients with PLF-AS. METHODS AND RESULTS: Between 2000 and 2010, 677 patients with severe AS, preserved left ventricular ejection fraction, and aortic valve replacement were included (74±8 years; 42% women; aortic valve area, 0.69±0.16 cm(2)). A PLF (indexed stroke volume ≤35 mL/m(2)) was found in 26%, and after aortic valve replacement, 54% of patients had PPM, defined as an indexed effective orifice area ≤0.85 cm(2)/m(2). The combined presence of PLF and PPM was found in 15%. Compared with patients with noPLF/noPPM, those with PLF/PPM were significantly older, with more comorbidities. They also received smaller and biological bioprosthesis more often (all P<0.01). Although early mortality was not significantly different between groups, the 10-year survival rate was significantly reduced in case of PLF/PPM compared with noPLF/noPPM (38±9% versus 70±5%; P=0.002), even after multivariable adjustment (hazard ratio, 2.58; 95% confidence interval, 1.5-4.45; P=0.0007). CONCLUSIONS: In this large catheterization-based study, the coexistence of PLF-AS before surgery and PPM after surgery is associated with the poorest outcome.