Prognostic Relevance of Global Myocardial Work Index in Patients with Moderate Aortic Valve Stenosis.

BACKGROUND: A reduced global myocardial work index (GWI) ≤ 1951 mmHg% is associated with increased mortality in patients with severe aortic valve stenosis (AS). However, parameters predicting the outcome in patients with moderate AS are limited. Therefore, the aim of this study was to evaluate the prognostic value of the GWI in patients with moderate AS. METHODS AND RESULTS: In this prospective study, 103 patients with moderate AS (mean age 72 ± 10 years; male: 69%) underwent standardized transthoracic echocardiography. The primary endpoint was survival without an aortic valve replacement (AVR). After a median follow-up of 30 ± 5 months, 37 patients (36%) were referred for an AVR. Survival without an AVR was 96% at 12 months and 80% at 30 months (>1951 mmHg%) versus 96% and 68% (≤1951 mmHg%). A GWI ≤ 1951 mmHg% did not predict the need for an AVR (hazard ratio 1.31 (95% CI, 0.63-2.72), p = 0.49). Furthermore, there was no significant correlation between the mean GWI (1644 ± 448 mmHg%) and mean aortic valve pressure gradient (24.2 mmHg ± 6.2, p = 0.615) or effective aortic orifice area (1.24 cm2 ± 0.11, p = 0.678). There was no difference between the AVR and non-AVR groups in the occurrence of clinical symptoms. CONCLUSION: In contrast to patients with severe AS, a GWI ≤ 1951 mmHg% did not predict the need for an AVR. Further research is needed to improve the risk stratification in patients with moderate AS.

Impact of Aortic Valve Regurgitation on Doppler Echocardiographic Parameters in Patients with Severe Aortic Valve Stenosis.

BACKGROUND: Diagnosing severe aortic stenosis (AS) depends on flow and pressure conditions. It is suspected that concomitant aortic regurgitation (AR) has an impact on the assessment of AS severity. The aim of this study was to analyze the impact of concomitant AR on Doppler-derived guideline criteria. We hypothesized that both transvalvular flow velocity (maxVAV) and the mean pressure gradient (mPGAV) will be affected by AR, whereas the effective orifice area (EOA) and the ratio between maximum velocity of the left ventricular outflow tract and transvalvular flow velocity (maxVLVOT/maxVAV) will not. Furthermore, we hypothesized that EOA (by continuity equation), and the geometric orifice area (GOA) (by planimetry using 3D transesophageal echocardiography, TEE), will not be affected by AR. METHODS AND RESULTS: In this retrospective study, 335 patients (mean age 75.9 ± 9.8 years, 44% male) with severe AS (defined by EOA < 1.0 cm2) who underwent a transthoracic and transesophageal echocardiography were analyzed. Patients with a reduced left ventricular ejection fraction (LVEF < 53%) were excluded (n = 97). The remaining 238 patients were divided into four subgroups depending on AR severity, and they were assessed using pressure half time (PHT) method: no, trace, mild (PHT 500-750 ms), and moderate AR (PHT 250-500 ms). maxVAV, mPGAV and maxVLVOT/maxVAV were assessed in all subgroups. Among the four subgroups (no (n = 101), trace (n = 49), mild (n = 61) and moderate AR (n = 27)), no differences were obtained for EOA (no AR: 0.75 cm2 ± 0.15; trace AR: 0.74 cm2 ± 0.14; mild AR: 0.75 cm2 ± 0.14; moderate AR: 0.75 cm2 ± 0.15, p = 0.998) and GOA (no AR: 0.78 cm2 ± 0.20; trace AR: 0.79 cm2 ± 0.15; mild AR: 0.82 cm2 ± 0.19; moderate AR: 0.83 cm2 ± 0.14, p = 0.424). In severe AS with moderate AR, compared with patients without AR, maxVAV (p = 0.005) and mPGAV (p = 0.022) were higher, whereas EOA (p = 0.998) and maxVLVOT/maxVAV (p = 0.243) did not differ. The EOA was smaller than the GOA in AS patients with trace (0.74 cm2 ± 0.14 vs. 0.79 cm2 ± 0.15, p = 0.024), mild (0.75 cm2 ± 0.14 vs. 0.82 cm2 ± 0.19, p = 0.021), and moderate AR (0.75 cm2 ± 0.15 vs. 0.83 cm2 ± 0.14, p = 0.024). In 40 (17%) patients with severe AS, according to an EOA < 1.0 cm2, the GOA was ≥ 1.0 cm2. CONCLUSION: In severe AS with moderate AR, the maxVAV and mPGAV are significantly affected by AR, whereas the EOA and maxVLVOT/maxVAV are not. These results highlight the potential risk of overestimating AS severity in combined aortic valve disease by only assessing transvalvular flow velocity and the mean pressure gradient. Furthermore, in cases of borderline EOA, of approximately 1.0 cm2, AS severity should be verified by determining the GOA.

Valid and Reproducible Quantitative Assessment of Cardiac Volumes by Echocardiography in Patients with Valvular Heart Diseases-Possible or Wishful Thinking?

The analysis of left ventricular function is predominantly based on left ventricular volume assessment. Especially in valvular heart diseases, the quantitative assessment of total and effective stroke volumes as well as regurgitant volumes is necessary for a quantitative approach to determine regurgitant volumes and regurgitant fraction. In the literature, there is an ongoing discussion about differences between cardiac volumes estimated by echocardiography and cardiac magnetic resonance tomography. This viewpoint focuses on the feasibility to assess comparable cardiac volumes with both modalities. The former underestimation of cardiac volumes determined by 2D and 3D echocardiography is presumably explained by methodological and technical limitations. Thus, this viewpoint aims to stimulate an urgent and critical rethinking of the echocardiographic assessment of patients with valvular heart diseases, especially valvular regurgitations, because the actual integrative approach might be too error prone to be continued in this form. It should be replaced or supplemented by a definitive quantitative approach. Valid quantitative assessment by echocardiography is feasible once echocardiography and data analysis are performed with methodological and technical considerations in mind. Unfortunately, implementation of this approach cannot generally be considered for real-world conditions.

Elucidation of the genetic causes of bicuspid aortic valve disease.

AIMS: The present study aims to characterize the genetic risk architecture of bicuspid aortic valve (BAV) disease, the most common congenital heart defect. METHODS AND RESULTS: We carried out a genome-wide association study (GWAS) including 2236 BAV patients and 11 604 controls. This led to the identification of a new risk locus for BAV on chromosome 3q29. The single nucleotide polymorphism rs2550262 was genome-wide significant BAV associated (P = 3.49 × 10-08) and was replicated in an independent case-control sample. The risk locus encodes a deleterious missense variant in MUC4 (p.Ala4821Ser), a gene that is involved in epithelial-to-mesenchymal transformation. Mechanistical studies in zebrafish revealed that loss of Muc4 led to a delay in cardiac valvular development suggesting that loss of MUC4 may also play a role in aortic valve malformation. The GWAS also confirmed previously reported BAV risk loci at PALMD (P = 3.97 × 10-16), GATA4 (P = 1.61 × 10-09), and TEX41 (P = 7.68 × 10-04). In addition, the genetic BAV architecture was examined beyond the single-marker level revealing that a substantial fraction of BAV heritability is polygenic and ∼20% of the observed heritability can be explained by our GWAS data. Furthermore, we used the largest human single-cell atlas for foetal gene expression and show that the transcriptome profile in endothelial cells is a major source contributing to BAV pathology. CONCLUSION: Our study provides a deeper understanding of the genetic risk architecture of BAV formation on the single marker and polygenic level.

Comparison of left ventricular deformation abnormalities by echocardiography with cardiac magnetic resonance imaging in patients with acute myocarditis and preserved left ventricular ejection fraction.

Purpose: Cardiac magnetic resonance imaging (cMRI) represents the gold standard to detect myocarditis. Left ventricular (LV) deformation imaging provides additional diagnostic options presumably exceeding conventional transthoracic echocardiography (TTE). The present study aimed to analyze the feasibility to detect myocarditis in patients (pts) with preserved LV ejection fraction (LVEF) by TTE compared to cMRI. It has been hypothesized that the number of pathological findings by deformation imaging correspond to findings in cMRI. Methods and results: Between January 2018 and February 2020 102 pts with acute myocarditis according to the modified Lake Louise criteria and early gadolinium enhancement (EGE) by cMRI were identified at the department of cardiology at the University Hospital Leipzig. Twenty-six pts were included in this retrospective comparative study based on specific selection criteria. Twelve pts with normal cMRI served as a control group. LV deformation was analyzed by global and regional longitudinal strain (GLS, rLS), global and regional circumferential and radial strain (GCS, rCS, GRS, rRS), and LV rotation (including layer strain analysis). All parameters were compared to findings of edema, inflammation, and fibrosis by cMRI according to Lake Louise criteria. All pts with acute myocarditis diagnosed by cMRI showed pathological findings in TTE. Especially rCS and LV rotation analyzed by regional layer strain exhibit a high concordance with pathological findings in cMRI. In controls no LV deformation abnormalities were documented. Mean values of GLS, GRS, and GCS were not significantly different between pts with acute myocarditis and controls. Conclusion: This retrospective analysis documents the feasibility of detecting regional deformation abnormalities by echocardiography in patients with acute myocarditis confirmed by cMRI. The detection of pathological findings due to myocarditis requires the determination of regional deformation parameters, particularly rCS and LV rotation. The assessment of global strain values does not appear to be of critical value.

Left ventricular hypertrophy, diastolic dysfunction and right ventricular load predict outcome in moderate aortic stenosis.

Aims: Predictors of progression of moderate aortic valve stenosis (AS) are incompletely understood. The objective of this study was to evaluate the prognostic value of left ventricular hypertrophy (LVH), diastolic dysfunction, and right ventricular (RV) load in moderate AS. Methods and results: Moderate AS was defined by aortic valve area (AVA), peak transvalvular velocity (Vmax) or mean pressure gradient (PGmean). A total of 131 Patients were divided into two groups according to the number of pathophysiological changes (LVH, diastolic dysfunction with increased LV filling pressures and/or RV load): <2 (group 1); ≥2 (group 2). The primary outcome was survival without aortic valve replacement (AVR). After follow-up of 30 months, the reduction of AVA (-0.06 ± 0.16 vs. -0.24 ± 0.19 cm2, P < 0.001), the increase of PGmean (2.89 ± 6.35 vs 6.29 ± 7.13 mmHg, P < 0.001) and the decrease of the global longitudinal strain (0.8 ± 2.56 vs. 1.57 ± 3.42%, P < 0.001) from baseline to follow-up were significantly more pronounced in group 2. Survival without AVR was 82% (group 1) and 56% (group 2) [HR 3.94 (1.74-8.94), P < 0.001]. Survival without AVR or progression of AS was 77% (group 1) and 46% (group 2) [HR 3.80 (1.84-7.86), P < 0.001]. The presence of ≥2 pathophysiological changes predicted outcome whereas age, comorbidities, LDL-cholesterol did not. Conclusion: The presence of ≥2 pathophysiological changes is a strong predictor of outcome in moderate AS and may be useful for risk stratification, particularly for scheduling follow-up time intervals and deciding the timing of AVR.

Left ventricular mechanical dispersion in flow-gradient patterns of severe aortic stenosis with narrow QRS complex.

Patients with severe aortic stenosis are classified according to flow-gradient patterns. We investigated whether left ventricular (LV) mechanical dispersion, a marker of dyssynchrony and predictor of mortality, is associated with low-flow status in aortic stenosis. 316 consecutive patients with aortic stenosis and QRS duration < 120 ms were included in the retrospective analysis. Patients with severe aortic stenosis (aortic valve area ≤ 1.0 cm2) were classified as normal-flow (NF; stroke volume index > 35 ml/m2) high-gradient (HG; mean transvalvular gradient ≥ 40 mmHg) (n = 79), NF low-gradient (LG) (n = 62), low-flow (LF) LG ejection fraction (EF) ≥ 50% (n = 57), and LF LG EF < 50% (n = 23). Patients with moderate aortic stenosis (aortic valve area 1.5-1.0 cm2; n = 95) served as comparison group. Mechanical dispersion (calculated as standard deviation of time from Q/S onset on electrocardiogram to peak longitudinal strain in 17 left ventricular segments) was similar in patients with NF HG (49.4 ± 14.7 ms), NF LG (43.5 ± 12.9 ms), LF LG EF ≥ 50% (47.2 ± 16.3 ms) and moderate aortic stenosis (44.2 ± 15.7 ms). In patients with LF LG EF < 50%, mechanical dispersion was increased (60.8 ± 20.7 ms, p < 0.05 vs. NF HG, NF LG, LF LG EF ≥ 50% and moderate AS). Mechanical dispersion correlated with global longitudinal strain (r = 0.1354, p = 0.0160) and heart rate (r = 0.1587, p = 0.0047), but not with parameters of aortic stenosis. Mechanical dispersion was similar among flow-gradient subgroups of severe aortic stenosis with preserved LVEF, but increased in patients with low-flow low-gradient and reduced LVEF. These findings indicate that mechanical dispersion is rather a marker of systolic myocardial dysfunction than of aortic stenosis.