Abstract-The myocardium of the failing heart undergoes a number of structural alterations, most notably hypertrophy of cardiac myocytes and an increase in extracellular matrix proteins, often seen as primary fibrosis. Connective tissue growth factor (CTGF) is a key molecule in the process of fibrosis and therefore seems an attractive therapeutic target. Regulation of CTGF expression at the promoter level has been studied extensively, but it is unknown how CTGF transcripts are regulated at the posttranscriptional level. Here we provide several lines of evidence to show that CTGF is importantly regulated by 2 major cardiac microRNAs (miRNAs), miR-133 and miR-30. First, the expression of both miRNAs was inversely related to the amount of CTGF in 2 rodent models of heart disease and in human pathological left ventricular hypertrophy. Second, in cultured cardiomyocytes and fibroblasts, knockdown of these miRNAs increased CTGF levels. Third, overexpression of miR-133 or miR-30c decreased CTGF levels, which was accompanied by decreased production of collagens. Fourth, we show that CTGF is a direct target of these miRNAs, because they directly interact with the 3Ј untranslated region of CTGF. Taken together, our results indicate that miR-133 and miR-30 importantly limit the production of CTGF. We also provide evidence that the decrease of these 2 miRNAs in pathological left ventricular hypertrophy allows CTGF levels to increase, which contributes to collagen synthesis. In conclusion, our results show that both miR-133 and miR-30 directly downregulate CTGF, a key profibrotic protein, and thereby establish an important role for these miRNAs in the control of structural changes in the extracellular matrix of the myocardium.

Aortic valve stenosis impairs subendocardial perfusion with a risk of irreversible subendocardial tissue damage. A likely precursor of damage is subendocardial contractile dysfunction, expressed by the parameter TransDif, which is defined as epicardial minus endocardial myofiber shortening, normalized to the mean value. With the use of magnetic resonance tagging in two short-axis slices of the left ventricle (LV), TransDif was derived from LV torsion and contraction during ejection. TransDif was determined in healthy volunteers (control, n = 9) and in patients with aortic valve stenosis before (AVSten, n = 9) and 3 mo after valve replacement (AVRepl, n = 7). In the control group, TransDif was 0.00 ± 0.14 (mean ± SD). In the AVSten group, TransDif increased to 0.96 ± 0.62, suggesting impairment of subendocardial myofiber shortening. In the AVRepl group, TransDif decreased to 0.37 ± 0.20 but was still elevated. In eight of nine AVSten patients, the TransDif value was elevated individually ( P < 0.001), suggesting that the noninvasively determined parameter TransDif may provide important information in planning of treatment of aortic valve stenosis.

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In patients with aortic stenosis, the left ventricular afterload is determined by the degree of valvular obstruction and the systemic arterial system. We developed an explicit mathematical model formulated with a limited number of independent parameters that describes the interaction among the left ventricle, an aortic stenosis, and the arterial system. This ventricularvalvular-vascular (V 3 ) model consists of the combination of the time-varying elastance model for the left ventricle, the instantaneous transvalvular pressure-flow relationship for the aortic valve, and the three-element windkessel representation of the vascular system. The objective of this study was to validate the V 3 model by using pressure-volume loop data obtained in six patients with severe aortic stenosis before and after aortic valve replacement. There was very good agreement between the estimated and the measured left ventricular and aortic pressure waveforms. The total relative error between estimated and measured pressures was on average (standard deviation) 7.5% (SD 2.3) and the equation of the corresponding regression line was y ϭ 0.99x Ϫ 2.36 with a coefficient of determination r 2 ϭ 0.98. There was also very good agreement between estimated and measured stroke volumes (y ϭ 1.03x ϩ 2.2, r 2 ϭ 0.96, SEE ϭ 2.8 ml). Hence, this mathematical V 3 model can be used to describe the hemodynamic interaction among the left ventricle, the aortic valve, and the systemic arterial system. mathematical modeling; cardiovascular system; cardiac catheterization; left ventricle LEFT VENTRICULAR (LV) pressure, aortic pressure, and cardiac output result from a matching among the oxygen demand of the body, the LV performance, and the LV afterload. The presence of an aortic valve stenosis causes an obstruction to LV outflow, thus resulting in an increase in LV afterload (20). Patients with aortic stenosis also often have concomitant diseases, including hypertension, hyperlipidemia, diabetes, and atherosclerosis (1,6,22,25). These diseases have been shown to alter the structural and functional properties of the systemic arterial system (8,40). More specifically, they may reduce arterial elasticity and/or increase arteriolar resistance. Hence in patients with aortic stenosis, the left ventricle is often facing a double load: a valvular load imposed by the aortic stenosis and an arterial load caused by a decrease in systemic arterial compliance (C) and/or an increase in systemic vascular resistance (R). Briand et al. (3) have recently shown that reduced C is a frequent occurrence in patients with aortic stenosis where it independently contributes to increase afterload and decrease LV function. In addition, Antonini-Canterin et al. (1) have reported that symptoms of aortic stenosis develop at a lesser degree of valvular obstruction in hypertensive compared with normotensive patients. It is thus important to assess the respective contributions of the aortic valve and the systemic arterial system to the LV workload in such patients. This information could be ...

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Our data showed that post-cardiac surgery infections occur more frequently in patients with predetermined risk factors. The amount of blood transfusions was integrally related to every type of postoperative infection.

OBJECTIVES Although in both the US and European guidelines the ‘heart team approach’ is a class I recommendation, supporting evidence is still lacking. Therefore, we sought to provide comparative survival data of patients with mitral valve disease referred to the general and the dedicated heart team. METHODS In this retrospective cohort, patients evaluated for mitral valve disease by a general heart team (2009–2014) and a dedicated mitral valve heart team (2014–2018) were included. Decision-making was recorded prospectively in heart team electronic forms. The end point was overall survival from decision of the heart team. RESULTS In total, 1145 patients were included of whom 641 (56%) were discussed by dedicated heart team and 504 (44%) by general heart team. At 5 years, survival probability was 0.74 [95% confidence interval (CI) 0.68–0.79] for the dedicated heart team group compared to 0.70 (95% CI 0.66–0.74, P = 0.040) for the general heart team. Relative risk of mortality adjusted for EuroSCORE II, treatment groups (surgical, transcatheter and non-intervention), mitral valve pathology (degenerative, functional, rheumatic and others) and 13 other baseline characteristics for patients in the dedicated heart team was 29% lower [hazard ratio (HR) 0.71, 95% CI 0.54–0.95; P = 0.019] than for the general heart team. The adjusted relative risk of mortality was 61% lower for patients following the advice of the heart team (HR 0.39, 95% CI 0.25–0.62; P &lt; 0.001) and 43% lower for patients following the advice of the general heart team (HR 0.57, 95% CI 0.37–0.87; P = 0.010) compared to those who did not follow the advice of the heart team. CONCLUSIONS In this retrospective cohort, patients treated for mitral valve disease based on a dedicated heart team decision have significantly higher survival independent of the allocated treatment, mitral valve pathology and baseline characteristics.

Objectives Thoracoscopic ablation for atrial fibrillation (AF) and minimally invasive direct coronary artery bypass (MIDCAB) with robot-assisted left internal mammary artery (LIMA) harvesting may represent a safe and effective alternative to more invasive surgical approaches via sternotomy. The aim of our study was to describe the feasibility, safety and efficacy of a unilateral left-sided thoracoscopic AF ablation and concomitant MIDCAB surgery. Methods Retrospective analysis of a prospectively gathered cohort was performed of all consecutive patients with AF and at least a critical left anterior descending artery (LAD) stenosis that underwent unilateral left-sided thoracoscopic AF ablation and concomitant off-pump MIDCAB surgery in the Maastricht University Medical Centre between 2017 and 2021. Results Twenty-three patients were included (age 69 years (standard deviation = 8), paroxysmal AF 61%, left atrial volume index 42 ml/m2 (standard deviation = 11)). Unilateral left-sided thoracoscopic isolation of the left (n = 23) and right (n = 22) pulmonary veins and box (n = 21) by radiofrequency ablation was succeeded by epicardial validation of exit- and entrance block (n = 22). All patients received robot-assisted LIMA harvesting and off-pump LIMA-LAD anastomosis through a left mini-thoracotomy. Perioperative complications consisted of one bleeding of the thoracotomy wound and one aborted myocardial infarction not requiring intervention. Mean duration of hospital stay was 6 days (standard deviation = 2). After discharge, cardiac hospital readmission occurred in four patients (AF n = 1; pleural- and pericardial effusion n = 2, myocardial infarction requiring percutaneous intervention of the LIMA-LAD n = 1) within one year. After 12 months, 17/21 (81%) patients were in sinus rhythm when allowing anti-arrhythmic drugs. Finally, the left atrial ejection fraction improved postoperatively (26% (standard deviation = 11) to 38% (standard deviation = 7), P = 0.01). Conclusions In this initial feasibility and early safety study, unilateral left-sided thoracoscopic AF ablation and concomitant MIDCAB for LIMA-LAD grafting is a feasible, safe and efficacious for patients with AF and a critical LAD stenosis.