The Impact of Size and Position of a Mechanical Expandable Transcatheter Aortic Valve: Novel Insights Through Computational Modelling and Simulation Abstract Transcatheter aortic valve implantation has become an established procedure to treat severe aortic stenosis. Correct device sizing/positioning is crucial for optimal outcome. Lotus valve sizing is based upon multiple aortic root dimensions. Hence, it often occurs that two valve sizes can be selected. In this study, patient-specific computer simulation is adopted to evaluate the influence of Lotus size/position on paravalvular aortic regurgitation (AR) and conduction abnormalities, in patients with equivocal aortic root dimensions. First, simulation was performed in 62 patients to validate the model in terms of predicted AR and conduction abnormalities using postoperative echocardiographic, angiographic and ECG-based data. Then, two Lotus sizes were simulated at two positions in patients with equivocal aortic root dimensions. Large valve size and deep position were associated with higher contact pressure, while only large size, not position, significantly reduced the predicted AR. Despite general trends, simulations revealed that optimal device size/position is patient-specific.

Oxidised Low-Density Lipoprotein and Its Receptor-Mediated Endothelial Dysfunction Are Associated with Coronary Artery Lesions in Kawasaki Disease Abstract The study aimed to investigate the role of oxidised low-density lipoprotein (oxLDL)/lectin-like-oxLDL receptor-1 (LOX-1) in coronary artery lesions (CALs) in Kawasaki disease (KD) and of plasma oxLDL concentration in the early prediction of CALs in KD. This prospective study included 80 KD patients, 20 febrile and 20 healthy children. oxLDL, LOX-1 and other parameters were analysed in the acute phase. Plasma oxLDL concentration and LOX-1 mRNA expression in peripheral blood mononuclear cells (PBMCs) were significantly increased in KD patients compared with febrile and healthy children (P < 0.001 and P = 0.022, respectively), particularly in the group with CALs (P < 0.001 and P = 0.027, respectively). Coronary Z-score was significantly correlated with plasma oxLDL concentration and LOX-1 mRNA expression (r = 0.739 and 0.637, respectively; P < 0.01). The sensitivity and specificity of predicting CALs were 71.4% and 77.2%, respectively, at plasma oxLDL concentration ≥ 12.38 mU/L. oxLDL/LOX-1 may be involved in CAL development. The plasma oxLDL concentration in the acute phase is a potentially useful biological indicator for predicting CAL in KD patients.

Gender Differences in Cardiac Hypertrophy Abstract Cardiac hypertrophy is an adaptive response to abnormal physiological and pathological stimuli, which can be classified into concentric and eccentric hypertrophy, induced by pressure overload or volume overload, respectively. In both physiological and pathological scenarios, females generally show a more favorable form of hypertrophy compared with their male counterparts. However once established, cardiac hypertrophy is a stronger risk factor for heart failure in females. Pre-menopausal women are better protected against cardiac hypertrophy compared with men, but this protection is abolished following menopause and is partially restored after estrogen replacement therapy. Estrogen exerts its protection by counteracting pro-hypertrophy signaling pathways, whereas androgen mostly plays an opposite role in cardiac hypertrophy. We here summarize the progress in the understanding of sexual dimorphisms in cardiac hypertrophy and highlight recent breakthroughs in the regulatory role of sex hormones and their intricate molecular networks, in order to shed light on gender-oriented therapeutic efficacy for pathological hypertrophy.

Correction to: Usefulness of Genetic Testing in Hypertrophic Cardiomyopathy: an Analysis Using Real-World Data The name of author M. Alejandra Restrepo-Cordoba was parsed incorrectly (in such a way as to suggest that her surname is “Alejandra Restrepo-Cordoba”) in this article as published.

A Durable Porcine Pericardial Surgical Bioprosthetic Heart Valve: a Proof of Concept Abstract Bioprosthetic leaflets made from animal tissues are used in the majority of surgical and transcatheter cardiac valve replacements. This study develops a new surgical bioprosthesis, using porcine pericardial leaflets. Porcine pericardium was obtained from genetically engineered pigs with a mutation in the GGTA-1 gene (GTKO) and fixed in 0.6% glutaraldehyde, and used to develop a new surgical valve design. The valves underwent in vitro hydrodynamic test in a pulse duplicator and high-cycled accelerated wear testing and were evaluated for acute haemodynamics and thrombogenicity in a juvenile sheep implant study for 48 h. The porcine surgical pericardial heart valves (pSPHVs) exhibited excellent hydrodynamics and reached 200 million cycles of in vitro durability, with no observable damage. Juvenile sheep implants demonstrated normal valve function with no acute thrombogenic response for either material. The pSPHV incorporates a minimalistic construction method using a tissue-to-tissue design to cover the stent. This new design is a proof of concept alternative to the use of bovine pericardium and synthetic fabric in surgical bioprosthetic heart valves.

Profound Increase of Lung Airway Resistance in Heart Failure: a Potential Important Contributor for Dyspnea Abstract Dyspnea is a major symptom of heart failure (HF). Here, we have studied the lung remodeling and airway resistance in HF mice. We demonstrated that aortic banding–induced HF caused a dramatic decrease of lung compliance and an increase of lung airway resistance. The decrease of lung compliance was correlated with the increased lung weight in a linear fashion (γ2 = 0.824). An HF-induced increase of lung airway resistance and a decrease of lung compliance were almost identical in anesthetized mice and in the isolated lungs from these mice. HF caused profound lung fibrosis in mice with increased lung weight. Moreover, HF patients of NYHA class III–IV showed increased lung density as revealed by high-resolution CT scanning. These data indicate that lung compliance and lung airway resistance may be useful in determining lung remodeling after HF, and lung structure changes may contribute to dyspnea in HF.

Amiodarone Treatment in the Early Phase of Acute Myocardial Infarction Protects Against Ventricular Fibrillation in a Porcine Model Abstract Ventricular fibrillation (VF) occurring in the first minutes to hours of acute myocardial infarction (AMI) is a frequent cause of death and treatment options are limited. The aim was to test whether early infusion of amiodarone 10 min after onset of AMI reduced the incidence of VF in a porcine model. Eighteen female Danish landrace pigs were randomized to a control and an amiodarone group. AMI was induced by ligation of the mid-left anterior descending artery for 120 min followed by 60 min of reperfusion. VF occurred in 0/8 pigs treated with amiodarone compared to 7/10 controls (P < 0.01). Amiodarone treatment prolonged RR intervals, reduced dispersion of action potential duration in the infarcted area and mean number of ectopic beats. No negative effects on cardiac output and blood pressure were observed with amiodarone. Amiodarone qualifies as a potential drug candidate to prevent VF in the first minutes to hours of AMI.

Upregulation of Circulating Cardiomyocyte-Enriched miR-1 and miR-133 Associate with the Risk of Coronary Artery Disease in Type 2 Diabetes Patients and Serve as Potential Biomarkers Abstract Circulating miRNAs are increasingly suggested as clinical biomarker for diseases. We evaluated the expression of circulating cardiomyocyte-enriched miR-1 and miR-133 by real-time PCR in blood from patients with type 2 diabetes (T2D) without and with coronary artery disease (CAD) and healthy controls, investigated their association with the risk of CAD risk and their potential as biomarkers. The two miRNAs were upregulated in patients with T2D and CAD compared with controls, associated with CAD risk and remained significant after adjustment for multiple confounders. LDL-C was a positive predictor for miR-1 and miR-133, and mean blood pressure was also a positive predictor for miR-133. Both miRNAs strongly distinguished CAD from controls. miR-1 significantly distinguished CAD from T2D with higher diagnostic ability than miR-133, whereas the miR-1/miR-133 combination improved the diagnostic value. Upregulation of circulating miR-1 and miR-133 associate with the risk of CAD in T2D patients and may serve as diagnostic biomarkers.

Ex Vivo Pilot Study of Cardiac Magnetic Resonance Velocity Mapping for Quantification of Aortic Regurgitation in a Porcine Model in the Presence of a Transcatheter Heart Valve Abstract Accuracy of aortic regurgitation (AR) quantification by magnetic resonance (MR) imaging in the presence of a transcatheter heart valve (THV) remains to be established. We evaluated the accuracy of cardiac MR velocity mapping for quantification of antegrade flow (AF) and retrograde flow (RF) across a THV and the optimal slice position to use in cardiac MR imaging. In a systematic and fully controlled laboratory ex vivo setting, two THVs (Edwards SAPIEN XT, Medtronic CoreValve) were tested in a porcine model (n = 1) under steady flow conditions. Results showed a high level of accuracy and precision. For both THVs, AF was best measured at left ventricular outflow tract level, and RF at ascending aorta level. At these levels, MR had an excellent repeatability (ICC > 0.99), with a tendency to overestimate (4.6 ± 2.4% to 9.4 ± 7.0%). Quantification of AR by MR velocity mapping in the presence of a THV was accurate, precise, and repeatable in this pilot study, when corrected for the systematic error and when the best MR slice position was used. Confirmation of these results in future clinical studies would be a step forward in increasing the accuracy of the assessment of paravalvular AR severity.

Association of Genetic Polymorphisms in the Beta-1 Adrenergic Receptor with Recovery of Left Ventricular Ejection Fraction in Patients with Heart Failure Abstract Two common genetic polymorphisms in the beta-1 adrenergic receptor (ADRB1 Ser49Gly [rs1801252] and Arg389Gly [rs1801253]) significantly affect receptor function in vitro. The objective of this study was to determine whether ADRB1 Ser49Gly and Arg389Gly are associated with recovery of left ventricular ejection fraction (LVEF) in patients with heart failure. Patients with heart failure and baseline LVEF ≤ 40% were genotyped (n = 98), and retrospective chart review assessed the primary outcome of LVEF recovery to ≥ 40%. Un/adjusted logistic regression models revealed that Ser49Gly, but not Arg389Gly, was significantly associated with LVEF recovery in a dominant genetic model. The adjusted odds ratio for Ser49 was 8.2 (95% CI = 2.1–32.9; p = 0.003), and it was the strongest predictor of LVEF recovery among multiple clinical variables. In conclusion, patients with heart failure and reduced ejection fraction that are homozygous for ADRB1 Ser49 were significantly more likely to experience LVEF recovery than Gly49 carriers.