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The aim of the study was to assess the occurrence of classic risk factors in the study group of patients with heart failure and to link them with the transcriptional activity of the examined genes: metalloproteinase 9 (MMP-9) and the tissue inhibitor of metalloproteinases 1 (TIMP-1) . A total of 150 (100%) patients qualified for the study, including 80 (53.33%) patients with heart failure in the course of coronary artery disease, 40 (26.67%) with coronary artery disease without heart failure, and 30 (20.00%) in whom the presence of atherosclerotic changes in the coronary arteries was excluded. The material for molecular tests was peripheral blood collected from patients within the first 24 h of hospitalisation. A quantitative analysis of transcriptional activity was performed using the RT-qPCR technique. The most common classic risk factors among the patients in the study group were arterial hypertension (117; 78.00%) and overweight/obesity (102; 68%). In the group of patients with coronary artery disease and heart failure burdened with overweight/obesity, a significantly higher transcriptional activity of the metalloproteinase 9 (MMP-9) gene was found in comparison to patients who were not burdened with this risk factor. The analysis also showed the statistically significant higher transcriptional activity of the metalloproteinase 9 (MMP-9) gene in a group of patients with coronary artery disease and heart failure who smoked. The examined patients with heart failure due to myocardial ischemia were burdened with numerous cardiovascular risk factors, the most common of which were arterial hypertension, obesity/overweight, and hypercholesterolemia. A significant increase in the transcriptional activity of the metalloproteinase 9 (MMP-9) gene in the presence of risk factors (male sex, overweight/obesity, smoking) indicates another pathomechanism of their action and participation in the development and progression of heart failure during myocardial ischemia. There is a need for systematic information and educational activities promoting a healthy lifestyle with the elimination of modifiable risk factors for cardiovascular diseases.

Introduction: Drug therapy to reduce the regurgitation fraction (RF) of high-grade aortic regurgitation (AR) by increasing heart rate (HR) is generally recommended. However, chronic HR reduction in HFREF patients can significantly improve aortic compliance and thereby potentially decrease RF. To clarify these contrasts, we examined the influence of HR, aortic compliance and stroke volume (SV) on RF in an ex vivo porcine model of severe AR., Methods: Experiments were performed on porcine ascending aorta with aortic valves (n=12). Compliance was varied by inserting a Dacron graft close to the aortic valve. Both tube systems were connected to a left heart simulator varying HR and SV. AR was accomplished by punching a 0.3 cm 2 hole in one aortic cusp. Flow, RF, SV and aortic pressure were measured, aortic compliance with transoesophageal ultrasound probes., Results: Compliance of the aorta was significantly reduced after Dacron graft insertion (0.55%±0.21%/mm Hg vs 0.01%±0.007%/mm Hg, p<0.001, respectively). With increasing HR, RF was significantly reduced in each steady state of the native aorta (HR 40 bpm: 88%±7% vs HR 120 bpm: 42%±10%; p<0.001), but Dacron tube did not affect RF (HR 40 bpm: 87%±8%; p=0.79; HR 120 bpm: 42%±3%; p=0.86). Increasing SV also reduced RF independent of the stiff Dacron graft., Conclusion: Aortic compliance did not affect AR in the ex vivo porcine model of AR. RF was significantly reduced with increasing HR and SV. These results affirm that HR lowering and negative inotropic drugs should be avoided to treat severe AR., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The out-of-hospital cardiac arrest (OHCA) in the young may be associated with a genetic predisposition which is relevant even for genetic counseling of relatives. The identification of genetic variants depends on the availability of intact genomic DNA. DNA from autopsy may be not available due to low autopsy frequencies or not suitable for high-throughput DNA sequencing (NGS). The emergency medical service (EMS) plays an important role to save biomaterial for subsequent molecular autopsy. It is not known whether the DNA integrity of samples collected by the EMS is better suited for NGS than autopsy specimens., Material and Methods: DNA integrity was analyzed by standardized protocols. Fourteen blood samples collected by the EMS and biomaterials from autopsy were compared. We collected 172 autopsy samples from different tissues and blood with postmortem intervals of 14-168 h. For comparison, DNA integrity derived from blood stored under experimental conditions was checked against autopsy blood after different time intervals., Results: DNA integrity and extraction yield were higher in EMS blood compared to any autopsy tissue. DNA stability in autopsy specimens was highly variable and had unpredictable quality. In contrast, collecting blood samples by the EMS is feasible and delivered comparably the highest DNA integrity., Conclusions: Isolation yield and DNA integrity from blood samples collected by the EMS is superior in comparison to autopsy specimens. DNA from blood samples collected by the EMS on scene is stable at room temperature or even for days at 4 °C. We conclude that the EMS personnel should always save a blood sample of young fatal OHCA cases died on scene to enable subsequent genetic analysis., (© 2023. The Author(s).)

Objectives: Left atrial appendage (LAA) amputation concomitant to coronary artery bypass grafting (CABG) has become an increasingly performed technique in patients with atrial fibrillation (AF) or with sinus rhythm and a CHA2DS2-VASc score ≥2. However, LAA amputation has come under suspicion to cause postoperative atrial fibrillation (POAF) due to left atrial (LA) dilation. This study aims to assess this assumption in patients undergoing CABG in off-pump technique with and without amputation of the LAA., Methods: Patients who underwent isolated CABG in off-pump technique without history of AF were retrospectively examined. Cohorts were divided according to the concomitant execution of LAA amputation. LA volume was measured by transthoracic echocardiography and rhythm was analyzed by electrocardiography, medication protocol, and visit documentation. Propensity score (PS) matching was performed based on 20 preoperative risk variables to correct for selection bias., Results: A total of 1,522 patients were enrolled, with 1,267 in the control group and 255 in the LAA amputation group. Occurrence of POAF was compared in 243 PS-matched patient pairs. Neither the unmatched cohort (odds ratio [OR] 0.82; 95% confidence interval or CI [0.61; 1.11], p  = 0.19) nor the PS-matched cohort (OR 0.94; 95% CI [0.62; 1.41], p  = 0.75) showed significant differences in POAF occurrence. Subgroup analysis of sex, use of β-blockers, pulmonary disease, ejection fraction, and CHA2DS2-VASc-Score also showed no tendencies. LA volume did not change significantly ( p  = 0.18, 95% CI [-0.29; 1.51])., Conclusion: Surgical amputation of the LAA concomitant to CABG did not lead to LA dilation and has no significant impact on the occurrence of POAF., Competing Interests: None declared., (Thieme. All rights reserved.)

Objectives: Early right-sided heart failure (RHF) was seen in 22% of recipients of a left ventricular assist device (LVAD) in the European Registry for Patients with Mechanical Circulatory Support (EUROMACS). However, the optimal treatment of post-LVAD RHF is not well known. Levosimendan has proven to be effective in patients with cardiogenic shock and in those with end-stage heart failure. We sought to evaluate the efficacy of levosimendan on post-LVAD RHF and 30-day and 1-year mortality., Methods: The EUROMACS Registry was used to identify adults with mainstream continuous-flow LVAD implants who were treated with preoperative levosimendan compared to a propensity matched control cohort., Results: In total, 3661 patients received mainstream LVAD, of which 399 (11%) were treated with levosimendan pre-LVAD. Patients given levosimendan had a higher EUROMACS RHF score [4 (2- 5.5) vs 2 (2- 4); P < 0.001], received more right ventricular assist devices (RVAD) [32 (8%) vs 178 (5.5%); P = 0.038] and stayed longer in the intensive care unit post-LVAD implant [19 (8-35) vs 11(5-25); P < 0.001]. Yet, there was no significant difference in the rate of RHF, 30-day, or 1-year mortality. Also, in the matched cohort (357 patients taking levosimendan compared to an average of 622 controls across 20 imputations), we found no evidence for a difference in postoperative severe RHF, RVAD implant rate, length of stay in the intensive care unit or 30-day and 1-year mortality., Conclusions: In this analysis of the EUROMACS registry, we found no evidence for an association between levosimendan and early RHF or death, albeit patients taking levosimendan had much higher risk profiles. For a definitive conclusion, a multicentre, randomized study is warranted., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Right ventricular (RV) strain has provided valuable prognostic information for patients with cardiac amyloidosis (CA). However, the extent to which RV strain and strain rate can differentiate CA is not yet clinically established. CA underdiagnosis delays treatment strategies and exacerbates patient prognosis., Aims: Evaluation of cardiac magnetic resonance (CMR) quantified RV global and regional strain of CA and HCM patients along with CA subtypes., Methods: CMR feature tracking attained longitudinal, radial and circumferential global and regional strain in 47 control subjects (CTRL), 43 CA-, 20 hypertrophic cardiomyopathy- (HCM) patients. CA patients were subdivided in 21 transthyretin-related amyloidosis (ATTR) and 20 acquired immunoglobulin light chain (AL) patients. Strain data and baseline clinical parameters were statistically analysed with respect to diagnostic performance and discriminatory power between the different clinical entities., Results: Effective differentiation of CA from HCM patients was achieved utilizing global longitudinal (GLS: 16.5 ± 3.9% vs. -21.3 ± 6.7%, p = 0.032), radial (GRS: 11.7 ± 5.3% vs. 16.5 ± 7.1%, p < 0.001) and circumferential (GCS: -7.6 ± 4.0% vs. -9.4 ± 4.4%, p = 0.015) right ventricular strain. Highest strain-based hypertrophic phenotype differentiation was attained using GRS (AUC = 0.86). Binomial regression found right ventricular ejection fraction (RV-EF) (p = 0.017) to be a significant predictor of CA-HCM differentiation. CA subtypes had comparable cardiac strains., Conclusion: CMR-derived RV global strains and various regional longitudinal strains provide discriminative radiological features for CA-HCM differentiation. However, in terms of feasibility, cine-derived RV-EF quantification may suffice for efficient differential diagnostic support., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier B.V.)

Background: Cardiac amyloidosis (CA) manifests in a hypertrophic phenotype with a poor prognosis, making differentiation from hypertrophic cardiomyopathy (HCM) challenging and delaying early treatment. The extent to which magnetic resonance imaging (MRI) quantifies the right atrial strain (RAS) and strain rate (RASR), providing valuable diagnostic information, is not yet clinically established. Aims: This study assesses diagnostic differences in the longitudinal RAS and RASR between CA and HCM patients, control subjects (CTRL) and CA subtypes in addition to the impact of atrial fibrillation (AF) on the right atrial function in CA patients. The RAS and RASR of tricuspid regurgitation (TR) patients are used to assess the potential for diagnostic overlap. Methods: RAS and RASR quantification was conducted via MRI feature-tracking for biopsy-confirmed CA patients with subtypes identified. Strain parameters were compared for CTRL, HCM and TR patients. Post hoc testing identified intergroup differences. Results: In total, 41 CA patients were compared to 47 CTRL, 20 HCM and 31 TR patients. Reservoir (R), conduit and booster RAS and RASRs allow for significant differentiation (p < 0.001) between CA and HCM patients (R: 10.6 ± 14.3% vs. R: 33.5 ± 16.3%) and CTRL (R: 44.6 ± 15.7%). Booster and reservoir RAS and RASRs qualified as reliable diagnostic tests (AUC > 0.8). CA patients with AF, in contrast to sinus rhythm, demonstrated a significantly impaired reservoir RAS and RASR and booster RASR. The discriminative power of RAS for CA vs. TR was insufficient (R: 10.6% ± 14.3% vs. 7.0% ± 6.0%, p = 0.069). Differentiation between 21 transthyretin and 20 light-chain amyloidosis subtypes was not achievable (R: 0.7% ± 1.0% vs. 0.7% ± 1.0%, p = 0.827). Conclusion: The MRI-derived RAS and RASR are impaired in CA patients and may support noninvasive differentiation between CA, HCM and CTRL.

Background: This study challenges state-of-the-art cardiac amyloidosis (CA) diagnostics by feeding multi-chamber strain and cardiac function into supervised machine (SVM) learning algorithms., Methods: Forty-three CA (32 males; 79 years (IQR 71; 85)), 20 patients with hypertrophic cardiomyopathy (HCM, 10 males; 63.9 years (±7.4)) and 44 healthy controls (CTRL, 23 males; 56.3 years (IQR 52.5; 62.9)) received cardiovascular magnetic resonance imaging. Left atrial, right atrial and right ventricular strain parameters and cardiac function generated a 41-feature matrix for decision tree (DT), k-nearest neighbor (KNN), SVM linear and SVM radial basis function (RBF) kernel algorithm processing. A 10-feature principal component analysis (PCA) was conducted using SVM linear and RBF., Results: Forty-one features resulted in diagnostic accuracies of 87.9% (AUC = 0.960) for SVM linear, 90.9% (0.996; Precision = 94%; Sensitivity = 100%; F1-Score = 97%) using RBF kernel, 84.9% (0.970) for KNN, and 78.8% (0.787) for DT. The 10-feature PCA achieved 78.9% (0.962) via linear SVM and 81.8% (0.996) via RBF SVM. Explained variance presented bi-atrial longitudinal strain and left and right atrial ejection fraction as valuable CA predictors., Conclusion: SVM RBF kernel achieved competitive diagnostic accuracies under supervised conditions. Machine learning of multi-chamber cardiac strain and function may offer novel perspectives for non-contrast clinical decision-support systems in CA diagnostics.

Introduction and Objectives: The effect of a centrifugal continuous-flow left ventricular assist device (cfLVAD) on hemodynamic left ventricular unloading (HLVU) and the clinical conditions that interfere with hemodynamic optimization are not well defined., Methods: We retrospectively evaluated the likelihood of incomplete HLVU, defined as high pulmonary capillary wedge pressure (hPCWP)> 15mmHg in 104 ambulatory cfLVAD patients when the current standard recommendations for cfLVAD rotor speed setting were applied. We also evaluated the ability of clinical, hemodynamic and echocardiographic variables to predict hPCWP in ambulatory cfLVAD patients., Results: Twenty-eight percent of the patients showed hPCWP. The variables associated with a higher risk of hPCWP were age, central venous pressure, absence of treatment with renin-angiotensin-aldosterone system inhibitors, and brain natriuretic peptide levels. Patients with optimal HLVU had a 15.2±14.7% decrease in postoperative indexed left ventricular end-diastolic diameter compared with 8.9±11.8% in the group with hPCWP (P=.041). Independent predictors of hPCWP included brain natriuretic peptide and age. Brain natriuretic peptide <300 pg/mL predicted freedom from hPCWP with a negative predictive value of 86% (P <.0001)., Conclusions: An optimal HLVU can be achieved in up to 72% of the ambulatory cfLVAD patients when the current standard recommendations for rotor speed setting are applied. Age, central venous pressure and therapy with renin-angiotensin-aldosteron system inhibitors had a substantial effect on achieving this goal. Brain natriuretic peptide levels and the magnitude of reverse left ventricular remodeling seem to be useful noninvasive tools to evaluate HLVU in patients with functioning cfLVAD., (Copyright © 2021 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Left-atrial (LA) strain is the result of complex hemodynamics, which may be better characterized using a multiparametric approach. Cardiovascular magnetic resonance (CMR) feature tracking was used to perform a comprehensive LA strain assessment of 183 enrolled healthy volunteers (11-70 years, 97 females, median 32.9 ± 28.3 years). Novel strain dependencies were assessed using multi-parametric regression (MPR) analyses. LA volumetric data, left ventricular strain, transmitral and pulmonary venous blood flow parameters were utilized to create clusters for MPR of all subjects and a heart rate controlled subgroup (pulse: 60-75/min, N = 106). The LA reservoir(r) and conduit(c) strains of the total cohort were significantly elevated (p ≤ 0.001) in women (r: 49.7 ± 12.9%, c: 32.0 ± 11.0%) compared to men (r: 42.9 ± 11.4%, c: 26.1 IQ 10.5%). In contrast, there were no gender-specific differences (p > 0.05) for subgroup LA reservoir, conduit and booster(b) strains (all, r: 47.3 ± 12.7%; c: 29.0 IQ 15.5%; b: 17.6 ± 5.4%) and strain rates (all, 2.1 IQ 1.0 s -1 ; - 2.9 IQ 1.5 s -1 ; - 2.3 IQ 1.0 s -1 ). MPR found large effect sizes (|R 2 |≥ 0.26) for correlations between strain and various cardiac functional parameters. Largest effect size was found for the association between LA conduit strain and LA indexed booster volume, LA total ejection fraction, left ventricular global radial strain and E-wave (|R 2 |= 0.437). In addition to providing normal values for sex-dependent LA strain and strain rate, no gender differences were found with modified heart rate. MPR analyses of LA strain/strain rate and various cardiac functional parameters revealed that heart rate control improved goodness-of-fit for the overall model., (© 2022. The Author(s).)

Background: Genetics of sudden cardiac deaths (SCD) remains frequently undetected. Genetic analysis is recommended in undefined selected cases in the 2021 ERC-guideline. The emergency medical service and physicians (EMS) may play a pivotal role for unraveling SCD by saving biomaterial for later molecular autopsy. Since for high-throughput DNA-sequencing (NGS) high quality genomic DNA is needed. We investigated in a prospective proof-of-concept study the role of the EMS for the identification of genetic forms of SCDs in the young., Methods: We included patients aged 1-50 years with need for cardiopulmonary resuscitation attempts (CPR). Cases with non-natural deaths were excluded. In two German counties with 562,904 residents 39,506 services were analysed. Paired end panel-sequencing was performed, and variants were classified according to guidelines of the American College of Medical Genetics (ACMG)., Results: 769 CPR-attempts were recorded (1.95% of all EMS-services; CPR-incidence 68/100,000). In 103 cases CPR were performed in patients < 50y. 58% died on scene, 26% were discharged from hospital. 24 subjects were included for genotyping. Of these 33% died on scene, 37.5% were discharged from hospital. 25% of the genotyped patients were carriers of (likely) pathogenic (ACMG-4/-5) variants. 67% carried variants with unknown significance (ACMG-3). 2 of them had familial history for arrhythmogenic cardiomyopathy or had to be re-classified as ACMG-4 carriers due to whole exome sequencing., Conclusion: The EMS contributes especially in fatal OHCA-cases to increase the yield of identified genetic conditions by collecting a blood sample on scene. Thus, the EMS can contribute significantly to primary and secondary prophylaxis in affected families., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Currently, little is known about the genetic background of restrictive cardiomyopathy (RCM). Herein, we screened an index patient with RCM in combination with atrial fibrillation using a next generation sequencing (NGS) approach and identified the heterozygous mutation DES -c.735G>C. As DES -c.735G>C affects the last base pair of exon-3, it is unknown whether putative missense or splice site mutations are caused. Therefore, we applied nanopore amplicon sequencing revealing the expression of a transcript without exon-3 in the explanted myocardial tissue of the index patient. Western blot analysis verified this finding at the protein level. In addition, we performed cell culture experiments revealing an abnormal cytoplasmic aggregation of the truncated desmin form (p.D214-E245del) but not of the missense variant (p.E245D). In conclusion, we show that DES -c.735G>C causes a splicing defect leading to exon-3 skipping of the DES gene. DES -c.735G>C can be classified as a pathogenic mutation associated with RCM and atrial fibrillation. In the future, this finding might have relevance for the genetic understanding of similar cases.

Objectives: The development of late-onset right ventricular failure (LoRVF) that occurs months after a continuous-flow left ventricular assist device (LVAD) is implanted is a clinical problem that warrants investigation. Our goal was to study the incidence, clinical manifestations and prognosis of LoRVF in a population of patients who received an LVAD as bridge to transplantation., Methods: Data were analysed from 97 consecutive patients who received an LVAD as bridge to transplantation and underwent a right heart catheterization at least 3 months after receiving an LVAD implantation. LoRVF was defined if both haemodynamic criteria of a central venous pressure >16 mmHg and a cardiac index <2.3 l/min/m2 were present. Clinical and echocardiographic variables, hospitalizations for heart failure and survival were compared between patients with and without LoRVF., Results: LoRVF was diagnosed in 13% of patients after a median time of 11 months. Patients with LoRVF presented preoperative worse right ventricular (RV) dilatation and severe tricuspid regurgitation. LORVF was also associated with postoperative RV dilatation, moderate to severe tricuspid regurgitation and lower tricuspid annular plane systolic excursion. LoRVF resulted in increased brain natriuretic peptide levels and the need for diuretics, lower haemoglobin levels and a higher rate of atrial fibrillation and gastrointestinal bleeding. The rate of hospitalizations for heart failure in patients with LoRVF was 46%, and 15% required an urgent transplantation due to refractory RV failure. LoRVF decreased global survival and survival free from hospitalizations for heart failure (P < 0.0001)., Conclusions: LoRVF after the implantation of an LVAD as bridge to transplantation is associated with higher morbidity and lower survival. The results suggest that the routine use of a right heart catheterization and transthoracic echocardiography may contribute to an early diagnosis before further severe complications due to refractory RV failure might occur., Id Number of the Irb Approval: AZ-2019-521 on 10 July 2019., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

The risk of left ventricular (LV) and right ventricular (RV) maladaptation after surgery for isolated primary mitral regurgitation (PMR) is poorly defined. We aimed to evaluate LV and RV contractile function using speckle-tracking analysis alongside with quantification of exercise tolerance in patients with PMR after mitral valve surgery. All consecutive patients with symptomatic PMR undergoing mitral valve surgery between July 2015 and May 2017 were prospectively enrolled. Sequential echocardiographic studies along with clinical assessment were performed before and three months after surgery. Mean age in 138 patients was 65.8 ± 12.7 years, 48.2% (66) of whom were female. Mean LV ejection fraction decreased from 57 ± 12% to 50 ± 11% (p < 0.001), LV global longitudinal strain deteriorated from -19.2 ± 4.1% to -15.7 ± 3.8% (p < 0.001), and mechanical strain dispersion increased from 88 ± 12 to 117 ± 115 ms (p = 0.004). There was a reduction in tricuspid annulus plane systolic excursion from 22 ± 5 mm to 18 ± 4 mm (p < 0.001), as well as a slight deterioration of RV free wall mean longitudinal strain from -16.9 ± 5.6% to -15.7 ± 4.1% (p = 0.05). The rate of moderate to severe tricuspid regurgitation significantly decreased (p < 0.005). Regarding exercise tolerance, the New York Heart Association class improved (p < 0.001) and the walking distance increased (p < 0.001). During mid-term follow up after surgery for PMR, a deterioration of LV and RV contractile function measures could be observed. However, the clinical status, LV dimensions, and concomitant tricuspid regurgitation improved which in particular imply more effective RV contractile pattern.