Left atrial strain parameters derived by echocardiography are impaired in patients with acute myocarditis and preserved systolic left ventricular function

Purpose: Data derived by cardiac magnetic resonance (CMR) feature tracking suggest that not only left ventricular but also left atrial function is impaired in patients with acute myocarditis. Therefore, we investigated the diagnostic value of speckle tracking echocardiography of the left ventricle and left atrium in patients with acute myocarditis and normal left ventricular ejection fraction (LVEF). Methods and results: 30 patients with acute myocarditis confirmed by CMR according to the Lake Louise criteria and 20 healthy controls were analyzed including global longitudinal strain (GLS) and left atrial (LA) strain parameters. Although preserved LVEF was present in both groups, GLS was significantly lower in patients with acute myocarditis (GLS − 19.1 ± 1.8% vs. GLS − 22.1 ± 1.7%, p < 0.001). Further diastolic dysfunction measured by E/e’ mean was significantly deteriorated in the myocarditis group compared to the control group (E/e’ mean 6.4 ± 1.6 vs. 5.5 ± 1.0, p = 0.038). LA reservoir function (47.6 ± 10.4% vs. 55.5 ± 10.8%, p = 0.013) and LA conduit function (-33.0 ± 9.6% vs. -39.4 ± 9.5%, p = 0.024) were significantly reduced in patients with acute myocarditis compared to healthy controls. Also left atrial stiffness index (0.15 ± 0.05 vs. 0.10 ± 0.03, p = 0.003) as well as left atrial filling index (1.67 ± 0.47 vs. 1.29 ± 0.34, p = 0.004) were deteriorated in patients with myocarditis compared to the control group. Conclusion: In patients with acute myocarditis and preserved LVEF not only GLS but also LA reservoir function, LA conduit function and left atrial stiffness index as well as left atrial filling index were impaired compared to healthy controls indicating ventricular diastolic dysfunction and elevated LV filling pressures

Reduction of radiation exposure during transcatheter edge‐to‐edge mitral valve repair

Background Transcatheter mitral valve repair is an increasingly used therapy for mitral regurgitation which requires fluoroscopic guidance. Limiting radiation exposure during lengthy procedures is important for both patient and operator safety. This study aimed to investigate radiation dose during contemporary use of MitraClip implantation and the effects of a dose reduction program. Methods A total of 115 patients who underwent MitraClip implantation were prospectively enrolled in a single-center observational study. During the inclusion period, our institution adopted a radiation dose reduction program, comprising lowering of fluoroscopy pulse rate and image target dose. The first 58 patients were treated with conventional fluoroscopy settings, while the following 57 patients underwent the procedure with the newly implemented low dose protocol. Results Radiation dose area product significantly decreased after introduction of the low dose protocol (693 [366–1231] vs. 2265 [1517–3914] cGy·cm2, p < 0.001). After correcting for fluoroscopy time, gender and body mass index, the low dose protocol emerged as a strong negative predictor of radiation dose (p < 0.001), reducing dose area product by 64% (95% confidence interval [57–70]). Device time, device success, and procedural safety did not differ between the normal dose and low dose group. Furthermore, the low dose protocol was not associated with an increased incidence of a combined endpoint consisting of death, repeat intervention, or heart surgery during 12 months follow-up. Conclusion Reduction of radiation exposure during transcatheter mitral valve repair by 64% is feasible without affecting procedural success or safety

Predictors of functional improvement in the short term after MitraClip implantation in patients with secondary mitral regurgitation

Background and objectives MitraClip implantation is an established therapy for secondary mitral regurgitation (MR) in high-risk patients and has shown to improve several important outcome parameters such as functional capacity. Patient selection is both challenging and crucial for achieving therapeutic success. This study investigated baseline predictors of functional improvement as it was quantified by the six-minute walk distance (6MWD) after transcatheter mitral valve repair. Methods and results We retrospectively analyzed 79 patients with secondary MR treated with MitraClip implantation at an academic tertiary care center. Before and four weeks after the procedure, all patients underwent comprehensive clinical assessment, six-minute walk tests and echocardiography. 6MWD significantly improved after MitraClip therapy (295 m vs. 265 m, p < 0.001). A linear regression model including seven clinical baseline variables significantly predicted the change in 6MWD (p = 0.002, R-2 = 0.387). Female gender, diabetes mellitus and arterial hypertension were found to be significant negative predictors of 6MWD improvement. At baseline, female patients had significant higher left ventricular ejection fraction (49% vs. 42%, p = 0.019) and lower 6MWD (240 m vs. 288 m, p = 0.034) than male patients. Conclusion MitraClip implantation in secondary MR significantly improves functional capacity in high risk patients even in the short term of four weeks after the procedure. Female gender, diabetes mellitus and arterial hypertension are baseline predictors of a less favourable functional outcome. While further validation in a larger cohort is recommended, these parameters may improve patient selection for MitraClip therapy

Impact of transcatheter edge-to-edge mitral valve repair on central sleep apnoea

Aims Sleep-disordered breathing (SDB) and its subtype central sleep apnoea (CSA) are highly prevalent in patients with heart failure and associated with worse prognosis. Whereas pharmacological therapy of heart failure has been shown to ameliorate CSA, results from previous studies on the effect of mitral regurgitation therapy on SDB are contradicting. The aim of this study was to assess the impact of transcatheter edge-to-edge mitral valve repair (TEER) on prevalence and severity of CSA. Methods and results We enrolled 47 patients undergoing TEER for symptomatic mitral regurgitation in a prospective study. Secondary mitral regurgitation and left ventricular ejection fraction  50% reduction of both Apnoea-hypopnoea index and Cheyne-Stokes respiration. Conclusion TEER is associated with a significant short-term reduction of CSA and Cheyne-Stokes respiration in high-risk patients, strengthening its value as an effective treatment option for advanced heart failure

Acquired von Willebrand syndrome and factor VIII in patients with moderate to severe mitral regurgitation undergoing transcatheter mitral valve repair

Background and Hypothesis: The acquired von Willebrand syndrome (AvWS), which predisposes to bleeding events, is often related to valvular heart diseases. We investigated possible implications of AvWS and factor VIII levels in patients with moderate to severe mitral regurgitation (MR) undergoing transcatheter mitral valve repair (TMVR). Methods and Results: 123 patients with moderate to severe MR were prospectively enrolled. Complete measurements of von Willebrand Factor activity (vWFAct), von Willebrand Factor antigen (vWFAg), and factor VIII expression before and 4 weeks after TMVR were available in 85 patients. At baseline, seven patients had a history of gastrointestinal bleeding, two patients suffered bleeding events during their hospital stay, and one patient had a bleeding 4 weeks after TMVR. Even though vWFAct, vWFAct/vWFAg ratio and vWFAg values did not change after TMVR, we observed a significantly lower vWFAct/vWFAg ratio in patients with primary MR as compared to patients with secondary MR both at baseline (p = 0.022) and 4 weeks following the TMVR procedure (p = 0.003). Additionally, patients with a mean mitral valve gradient ≥4 mmHg after TMVR had significantly lower vWFAct/vWFAg ratios as compared to patients with a mean mitral valve gradient <4 mmHg (p = 0.001). Conclusions: MR of primary etiology was associated with lower vWFAct/vWFAg ratio, hinting toward HMWM loss due to shear stress caused by eccentric regurgitation jets. In addition, morphological changes leading to postprocedural transmitral gradients ≥4 mmHg were related to lower vWFAct/vWFAg ratio 4 weeks after the procedure. Alterations of the vWFAct/vWFAg ratio in turn did not translate into a greater risk for bleeding events

The impact of bicuspid aortic valve morphology on von Willebrand factor function in patients with severe aortic stenosis and its change after TAVI

Background Aortic stenosis (AS) can cause acquired von Willebrand syndrome (AVWS) and valve replacement has been shown to lead to von Willebrand factor (vWF) recovery. The aim of the current study was to investigate the prevalence of AVWS in different severe AS phenotypes and its course after transcatheter aortic valve implantation (TAVI). Methods 143 patients with severe AS undergoing TAVI were included in the study. vWF function was assessed at baseline, 6 and 24 h after TAVI. AVWS was defined as a reduced vWF:Ac/Ag ratio ≤ 0.7. Phenotypes were classified by tricuspid (TAV) and bicuspid (BAV) valve morphology, mean transvalvular gradient (Pmean), stroke volume index (SVI), ejection fraction (EF) and indexed effective orifice area (iEOA). Results AVWS was present in 36 (25.2%) patients before TAVI. vWF:Ac/Ag ratio was significantly lower in high gradient compared to low-gradient severe AS [0.78 (IQR 0.67–0.86) vs. 0.83 (IQR 0.74–0.93), p < 0.05] and in patients with BAV compared to TAV [0.70 (IQR 0.63–0.78) vs. 0.81 (IQR 0.71–0.89), p < 0.05]. Normalization of vWF:Ac/Ag ratio was achieved in 61% patients 24 h after TAVI. As in the overall study cohort, vWF:Ac/Ag ratio increased significantly in all severe AS subgroups 6 h after TAVI (each p < 0.05). Regarding binary logistic regression analysis, BAV was the only significant predictor for AVWS. Conclusions BAV morphology is a strong predictor for AVWS in severe AS. TAVI restores vWF function in most patients with severe AS independently of AS phenotype and valve morphology

Application of a functional model for the modernization of devices designed to eliminate emergency oil spills

The article describes the stages of creation and composition of the functional model, which can be used for the design of oil spill response devices. The principle of operation of the functional model given in the article and it's graphical scheme are show

A network analysis to identify mediators of germline-driven differences in breast cancer prognosis.

Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies ~7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A&gt;T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Evaluation of polygenic risk scores for breast and ovarian cancer risk prediction in BRCA1 and BRCA2 mutation carriers

Background: Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes BRCA1 or BRCA2. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates. Methods: We constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]-positive, and ER-negative) and for OC. Using data from 15 252 female BRCA1 and 8211 BRCA2 carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS. Results: The PRS for ER-negative BC displayed the strongest association with BC risk in BRCA1 carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, P = 8.2 x 10(53)). In BRCA2 carriers, the strongest association with BC risk was seen for the overall BC PRS (HR = 1.22, 95% CI = 1.17 to 1.28, P = 7.2 x 10(-20)). The OC PRS was strongly associated with OC risk for both BRCA1 and BRCA2 carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for BRCA2 carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS. Conclusions: BC and OC PRS are predictive of cancer risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management