Feasibility and agreement of a novel combined echocardiographic method to measure global longitudinal strain and strain rate compared to speckle tracking and tissue Doppler imaging.

Background: Currently, two echocardiographic techniques are used to measure deformation: tissue Doppler imaging (TDI) and speckle tracking echocardiography (STE). Recently, a technique combining STE and TDI (on TDI overlay images) has become available, allowing derivation of STE/TDI results from a single acquisition/reading (combined-STE/combined-TDI). We tested the feasibility and agreement of this novel technique to measure left ventricular deformation in the general population compared to STE and TDI.Methods: We examined a subsample of 106 consecutive subjects of the Asklepios Study, a population-based random sample of male/female volunteers without overt clinical disease (mean age: 55.9 years). Left ventricular deformation measurements were assessed with transthoracic echocardiography using the combined method, STE and TDI.Results: Almost all deformation parameters significantly differed between all methods. Global systolic longitudinal strain (GS) and strain rate (GSRs) values measured by combined-TDI were significantly higher (GS -17.2% ± 3.0, GSRs -0.9 s-1 ± 0.2) compared to TDI (GS -21.1% ± 2.2, GSRs -1.3 s-1 ± 0.2). Measurements by combined-STE were significantly lower (GS -19.1% ± 2.9, GSRs -1.0 s-1 ± 0.2) compared to STE (GS -18.2% ± 3.0, GSRs -0.9 s-1 ± 0.1). Overall, the smallest differences and highest agreement were observed between STE and combined-STE (GS r = 0.84, p < .001; GSRs r = 0.70, p < .001).Conclusions: The comparison of methods showed different values and poor agreement between the echocardiographic modalities. Regrettably, the combined method does not make it possible to obtain in a single image/measurement results that are comparable to STE and TDI data in the general population.

Allometric versus ratiometric normalization of left ventricular stroke volume by Doppler-echocardiography for outcome prediction in severe aortic stenosis with preserved ejection fraction.

BACKGROUND: Appropriate normalization methods to scale Doppler-derived stroke volume (SV) to body size in patients with aortic stenosis (AS) are poorly defined and reference values are lacking. We aim to establish reference values of normalized SV in adults, and to compare the prognostic value of SV normalized by different methods in AS patients. METHODS: In 2781 normotensive, non-obese adults without cardiovascular disease we defined normal relationships between SV and body size by nonlinear regression. Reference SV values were calculated by quantile regression. We subsequently analyzed by Cox analysis the prognostic performance of ratiometric and allometric normalized SV in 1450 patients with severe AS and preserved LVEF under medical and surgical management. RESULTS: Unlike ratiometric normalization, allometric indexation eliminated the residual relationships between normalized SV and body size. The allometric exponents that adequately described the SV-height (H) and SV-body surface area (BSA) relationships were 1.32, and respectively 0.88. In males, low-flow (LF) reference values were: <28 ml/m2, <30 ml/m, <30ml/(m2)0.88, and, respectively, <26 ml/m1.32, and in females <27 ml/m2, <28 ml/m, <29ml/(m2)0.88, and, respectively, <24 ml/m1.32. In patients with severe AS, SV/H1.32 was most consistently associated with mortality and showed better prognostic performance than other normalized SV parameters (adjusted hazard ratios: 1.86 for SV/H1.32, 1.72 for SV/H, 1.64 for SV/BSA, and 1.61 for SV/BSA0.88). Compared to H-normalization, BSA-normalization markedly overestimated the frequency of LF (3% vs. 9%). CONCLUSIONS: We provide normative reference values and appropriate normalization methods for SV by Doppler-echocardiography. In severe AS, SV/H1.32 seems the most appropriate indexation method, especially in obese individuals.

Muscle strength is a major determinant of the blood pressure response to isometric stress testing: the Asklepios population study.

AIM: Maximal handgrip strength is a strong predictor of cardiovascular mortality in economically and socioculturally diverse countries, yet the main determinants of cardiovascular response to change in afterload during handgrip are not well known. We examined the blood pressure (BP) responses during submaximal handgrip (at 25% of grip strength) and the determinants of grip strength. METHODS: We studied 2215 participants from a population-based random sample without overt clinical disease (Asklepios Study; mean age 56.2 years). Handgrip testing was performed using a modified Jamar dynamometer with direct visual feedback. Simultaneously, a validated finger plethysmographic device measured continuous BP and heart rate. RESULTS: During handgrip, SBP and DBP rose by, respectively, 20 ±â€Š13 and 10 ±â€Š6 mmHg. These changes were normally distributed and consistently higher in men. The main independent determinants of mean arterial pressure response during handgrip were: grip strength (F = 191.4; P < 0.001), baseline pulse pressure (F = 32.0; P < 0.001), height (F = 16.4; P < 0.001) and age (F = 12.8; P < 0.001). Grip strength was associated with muscle mass, better metabolic health, but also with higher baseline DBP. There was a significant graded increase in maximum pressure achieved and in the magnitude of pressure change during handgrip with increasing BP categories (P for trend <0.001). CONCLUSION: The population BP response to handgrip is variable and its predominant determinant turned out to be grip strength itself, which should be accounted for in future analyses. Higher baseline BP, even within the normotensive range, acted as an independent and graded predictor of BP increase during handgrip.

Effect of Obesity on Left Atrial Strain in Persons Aged 35-55 Years (The Asklepios Study).

Obesity increases the risk of heart failure and atrial fibrillation. Left atrial (LA) dysfunction is increasingly recognized as a mediator of cardiovascular disease. Early effects of obesity on LA function have not been examined in large population samples. We quantified LA strain and strain rate (SR) through speckle tracking echocardiography in 1,531 middle-aged community-based participants enrolled in the Asklepios study. We compared LA function between individuals with body mass index (BMI) < 25 kg/m2 (n = 779), 25 to 29.9 kg/m2 (n = 618) and ≥ 30 kg/m2 (n = 134). Significant differences in reservoir longitudinal LA strain (BMI < 25 kg/m2 = 35.3%, BMI 25-29.9 kg/m2 = 33.1%, and BMI ≥ 30 kg/m2 = 30.9%; p < 0.00001) strain rate ([SR] BMI < 25 kg/m2 = 151; BMI 25 to 29.9 kg/m2 = 141; and BMI ≥ 30 kg/m2 = 135 %/s; p <0.00001) and expansion index (BMI < 25 kg/m2 = 1.6, BMI 25 to 29.9 kg/m2 = 1.4, and BMI ≥ 30 kg/m2 = 1.4; p <0.00001) were seen, indicating reduced reservoir function with increasing BMI. Obesity was also associated with impaired LA conduit function, including conduit longitudinal LA strain (BMI < 25 kg/m2 = 21.6%, BMI 25 to 29.9 kg/m2 = 18.9%, and BMI ≥ 30 kg/m2 = 16.7%; p <0.00001), SR (BMI < 25 kg/m2 = -189, BMI 25 to 29.9 kg/m2 = 166, and BMI ≥ 30 kg/m2 = 150 %/s; p <0.0001) and passive LA emptying fraction (BMI < 25 kg/m2 = 40.5, BMI 25 to 29.9 kg/m2 = 36.5, and BMI ≥ 30 kg/m2 = 36%, p <0.00001). These differences persisted after adjustment for age, gender and other potential confounders. In contrast to reservoir and conduit function, obesity was associated with increased booster pump function (active LA emptying fraction: BMI < 25 kg/m2 = 19.4%, BMI 25 to 29.9 kg/m2 = 20.5%, and BMI ≥ 30 kg/m2 = 21.5%; p <0.00001). In middle-aged adults, obesity is associated with impaired reservoir and conduit LA function and higher booster function, which may be compensatory. Loss of booster LA function, either because of more advanced LA dysfunction or atrial fibrillation, may play an important role in precipitating heart failure in obese individuals.

Myocarditis Elicits Dendritic Cell and Monocyte Infiltration in the Heart and Self-Antigen Presentation by Conventional Type 2 Dendritic Cells.

Autoimmune myocarditis often leads to dilated cardiomyopathy (DCM). Although T cell reactivity to cardiac self-antigen is common in the disease, it is unknown which antigen presenting cell (APC) triggers autoimmunity. Experimental autoimmune myocarditis (EAM) was induced by immunizing mice with α-myosin loaded bone marrow APCs cultured in GM-CSF. APCs found in such cultures include conventional type 2 CD11b+ cDCs (GM-cDC2s) and monocyte-derived cells (GM-MCs). However, only α-myosin loaded GM-cDC2s could induce EAM. We also studied antigen presenting capacity of endogenous type 1 CD24+ cDCs (cDC1s), cDC2s, and MCs for α-myosin-specific TCR-transgenic TCR-M CD4+ T cells. After EAM induction, all cardiac APCs significantly increased and cDCs migrated to the heart-draining mediastinal lymph node (LN). Primarily cDC2s presented α-myosin to TCR-M cells and induced Th1/Th17 differentiation. Loss of IRF4 in Irf4fl/fl.Cd11cCre mice reduced MHCII expression on GM-cDC2s in vitro and cDC2 migration in vivo. However, partly defective cDC2 functions in Irf4fl/fl.Cd11cCre mice did not suppress EAM. MCs were the largest APC subset in the inflamed heart and produced pro-inflammatory cytokines. Targeting APC populations could be exploited in the design of new therapies for cardiac autoimmunity.

Leukocyte telomere length and diet in the apparently healthy, middle-aged Asklepios population.

Telomere length is a prognostic biomarker for aging diseases. As it is unknown whether diet plays a role in these associations, we aimed to assess the impact of diet on telomere length. Moreover, given that telomere length is modulated by oxidative stress and inflammation, an additional goal was to evaluate whether the latter may mediate possible telomere - diet associations. Southern blot measured leukocyte telomere length and food frequency questionnaire data were compared for 2509 apparently healthy men and women (~35 to 55 years) from the Asklepios population. No significant associations were found between telomere length and overall dietary characteristics, such as dietary diversity, quality, equilibrium, and the dietary inflammatory index. Exploratory analysis of individual dietary variables revealed that a higher daily intake of deep fried potato products was associated with shorter telomeres (P = 0.002, 151 bp per 100 g/day), also in both sexes separately. Deep fried potato product consumption was also significantly associated with C-reactive protein (P = 0.032) and uric acid (P = 0.042), but not other inflammation and oxidative stress markers. These results suggest an at most limited association between overall dietary patterns and telomere length in the general population. Nevertheless, the association between telomere length and deep fried potato product intake warrants additional research.