Endothelial Function, Carotid-Femoral Stiffness, and Plasma Matrix Metalloproteinase-2 in Men With Bicuspid Aortic Valve and Dilated Aorta

Objectives: This study sought to examine the relationship between proximal aortic dilation and systemic vascular function in men with bicuspid aortic valve (BAV). Background: Proximal aortic dilation in subjects with BAV is associated with structural and functional abnormalities in the ascending aorta. Methods: We studied 32 men (median age 31 years [range 28 to 32 years]) with nonstenotic BAV categorized into 2 subgroups according to proximal ascending aorta dimensions (nondilated ≤35 mm and dilated ≥40 mm, respectively). Sixteen healthy men were studied as control subjects. Flow-mediated dilation in response to hyperemia (a marker of endothelial dysfunction) and carotid-femoral pulse wave velocity (an index of aortic stiffness) were assessed, and peripheral blood was sampled for matrix metalloproteinases (MMP-2 and -9) and their tissue inhibitors (TIMP-1 and -2), respectively. Cardiac chamber and aortic dimensions were assessed by echocardiography and cardiac magnetic resonance imaging, respectively. Results: Despite the similar severity of aortic stenosis, left ventricular mass, and function, men with dilated aortas had blunted brachial flow-mediated vasodilation to hyperemia (5% [interquartile range (IQR) 4% to 6%] vs. 8% [IQR 7% to 9%] change, p = 0.001), higher carotid-femoral pulse wave velocity (9.3 cm/s [IQR 9 to 10 cm/s] vs. 7 cm/s [IQR 6.9 to 7.4 cm/s], p = 0.001), and significantly higher plasma levels of MMP-2 (1,523 [IQR 1,460 to 1,674] vs. 1,036 [IQR 962 to 1,167], p = 0.001) compared with men with BAV and nondilated aorta. Values for MMP-9, TIMP-1 and -2 levels, and nitroglycerin-induced (endothelium-independent) vasodilation were similar in all 3 groups. Conclusions: Young men with BAV and dilated proximal aortas manifest systemic endothelial dysfunction, increased carotid-femoral pulse wave velocity, and higher plasma levels of MMP-2. These observations could introduce new targets for screening and perhaps for therapeutic intervention. © 2010 American College of Cardiology Foundation

An image fusion tool for echo‐guided left ventricular lead placement in cardiac resynchronization therapy: Performance and workflow integration analysis

Background The response rate to cardiac resynchronization therapy (CRT) may be improved if echocardiographic‐derived parameters are used to guide the left ventricular (LV) lead deployment. Tools to visually integrate deformation imaging and fluoroscopy to take advantage of the combined information are lacking. Methods An image fusion tool for echo‐guided LV lead placement in CRT was developed. A personalized average 3D cardiac model aided visualization of patient‐specific LV function in fluoroscopy. A set of coronary venography‐derived landmarks facilitated registration of the 3D model with fluoroscopy into a single multimodality image. The fusion was both performed and analyzed retrospectively in 30 cases. Baseline time‐to‐peak values from echocardiography speckle‐tracking radial strain traces were color‐coded onto the fused LV. LV segments with suspected scar tissue were excluded by cardiac magnetic resonance imaging. The postoperative augmented image was used to investigate: (a) registration accuracy and (b) agreement between LV pacing lead location, echo‐defined target segments, and CRT response. Results Registration time (264 ± 25 seconds) and accuracy (4.3 ± 2.3 mm) were found clinically acceptable. A good agreement between pacing location and echo‐suggested segments was found in 20 (out of 21) CRT responders. Perioperative integration of the proposed workflow was successfully tested in 2 patients. No additional radiation, compared with the existing workflow, was required. Conclusions The fusion tool facilitates understanding of the spatial relationship between the coronary veins and the LV function and may help targeted LV lead delivery

Left ventricular dysfunction in arrhythmogenic cardiomyopathy: Association with exercise exposure, genetic basis, and prognosis

Background Arrhythmogenic cardiomyopathy (AC) is characterized by biventricular dysfunction, exercise intolerance, and high risk of ventricular tachyarrhythmias and sudden death. Predisposing factors for left ventricular (LV) disease manifestation and its prognostic implication in AC are poorly described. We aimed to assess the associations of exercise exposure and genotype with LV dysfunction in AC, and to explore the impact of LV disease progression on adverse arrhythmic outcome. Methods and Results We included 168 patients with AC (50% probands, 45% women, 40±16 years old) with 715 echocardiographic exams (4.1±1.7 exams/patient, follow‐up 7.6 [interquartile range (IQR), 5.4–10.9] years) and complete exercise and genetic data in a longitudinal study. LV function by global longitudinal strain was −18.8% [IQR, −19.2% to −18.3%] at presentation and was worse in patients with greater exercise exposure (global longitudinal strain worsening, 0.09% [IQR, 0.01%–0.17%] per 5 MET‐hours/week, P=0.02). LV function by global longitudinal strain worsened, with 0.08% [IQR, 0.05%–0.12%] per year; (P<0.001), and progression was most evident in patients with desmoplakin genotype (P for interaction <0.001). Deterioration of LV function predicted incident ventricular tachyarrhythmia (aborted cardiac arrest, sustained ventricular tachycardia, or implantable cardioverter defibrillator shock) (adjusted odds ratio, 1.1 [IQR, 1.0–1.3] per 1% worsening by global longitudinal strain; P=0.02, adjusted for time and previous arrhythmic events). Conclusions Greater exercise exposure was associated with worse LV function at first visit of patients with AC but did not significantly affect the rate of LV progression during follow‐up. Progression of LV dysfunction was most pronounced in patients with desmoplakin genotypes. Deterioration of LV function during follow‐up predicted subsequent ventricular tachyarrhythmia and should be considered in risk stratification

Sex differences in disease progression and arrhythmic risk in patients with arrhythmogenic cardiomyopathy

Abstract Aims We aimed to assess sex-specific phenotypes and disease progression, and their relation to exercise, in arrhythmogenic cardiomyopathy (AC) patients. Methods and results In this longitudinal cohort study, we included consecutive patients with AC from a referral centre. We performed echocardiography at baseline and repeatedly during follow-up. Patients’ exercise dose at inclusion was expressed as metabolic equivalents of task (MET)-h/week. Ventricular arrhythmia (VA) was defined as aborted cardiac arrest, sustained ventricular tachycardia, or appropriate therapy by implantable cardioverter-defibrillator. We included 190 AC patients (45% female, 51% probands, age 41 ± 17 years). Ventricular arrhythmia had occurred at inclusion or occurred during follow-up in 85 patients (33% of females vs. 55% of males, P = 0.002). Exercise doses were higher in males compared with females [25 (interquartile range, IQR 14–51) vs. 12 (IQR 7–22) MET-h/week, P &amp;lt; 0.001]. Male sex was a marker of proband status [odds ratio (OR) 2.6, 95% confidence interval (CI) 1.4–5.0, P = 0.003] and a marker of VA (OR 2.6, 95% CI 1.4–5.0, P = 0.003), but not when adjusted for exercise dose and age (adjusted OR 1.8, 95% CI 0.9–3.6, P = 0.12 and 1.5, 95% CI 0.7–3.1, P = 0.30, by 5 MET-h/week increments). In all, 167 (88%) patients had ≥2 echocardiographic examinations during 6.9 (IQR 4.7–9.8) years of follow-up. We observed no sex differences in deterioration of right or left ventricular dimensions and functions. Conclusion Male AC patients were more often probands and had higher prevalence of VA than female patients, but not when adjusting for exercise dose. Importantly, disease progression was similar between male and female patients

Pregnancy and Progression of Cardiomyopathy in Women With LMNA Genotype‐Positive

Background We aimed to assess the association between number of pregnancies and long‐term progression of cardiac dysfunction, arrhythmias, and event‐free survival in women with pathogenic or likely pathogenic variants of gene encoding for Lamin A/C proteins ( LMNA+). Methods and Results We retrospectively included consecutive women with LMNA+ and recorded pregnancy data. We collected echocardiographic data, occurrence of atrial fibrillation, atrioventricular block, sustained ventricular arrhythmias, and implantation of cardiac electronic devices (implantable cardioverter defibrillator/cardiac resynchronization therapy defibrillator). We analyzed retrospectively complications during pregnancy and the peripartum period. We included 89 women with LMNA+ (28% probands, age 41±16 years), of which 60 had experienced pregnancy. Follow‐up time was 5 [interquartile range, 3–9] years. We analyzed 452 repeated echocardiographic examinations. Number of pregnancies was not associated with increased long‐term risk of atrial fibrillation, atrioventricular block, sustained ventricular arrhythmias, or implantable cardioverter defibrillator/cardiac resynchronization therapy defibrillator implantation. Women with previous pregnancy and nulliparous women had a similar annual deterioration of left ventricular ejection fraction (−0.5/year versus −0.3/year, P=0.37) and similar increase of left ventricular end‐diastolic diameter (0.1/year versus 0.2/year, P=0.09). Number of pregnancies did not decrease survival free from death, left ventricular assist device, or need for cardiac transplantation. Arrhythmias occurred during 9% of pregnancies. No increase in maternal and fetal complications was observed. Conclusions In our cohort of women with LMNA+, pregnancy did not seem associated with long‐term adverse disease progression or event‐free survival. Likewise, women with LMNA+ generally well‐tolerated pregnancy, with a small proportion of patients experiencing arrhythmias