Progressive Dilatation Research Articles

Abstract 15432: Post-Operative Systolic Dysfunction Following Aortic Root Replacement Surgery in Patients With Marfan Syndrome

Introduction: Cardiovascular disease is the leading cause of morbidity and premature mortality in Marfan Syndrome (MFS), with ≥ 50% of patients requiring prophylactic aortic root surgery for management of progressive aortic dilation. Given evidence for intrinsic myocardial dysfunction in MFS, patients may be at an increased risk of developing post-operative dysfunction and related cardiovascular complications following cardiac surgery. Our aim was to determine the prevalence, persistence, and long-term outcomes of post-operative ventricular dysfunction in MFS following aortic root replacement surgery. Methods: All adult patients with a confirmed diagnosis of MFS who underwent aortic root replacement surgery at Stanford from January 1995 to December 2021 were included. Post-operative systolic dysfunction was defined as a left ventricular ejection fraction (LVEF) <55% on transthoracic echocardiography at hospital discharge. Potential genetic, operative, and cardiac risk modifiers were also recorded. Results: There were 274 patients with MFS (64% male, 71% White) who underwent aortic root replacement surgery, followed over a median duration of 11 years (IQR 5, 16). Post-operative systolic dysfunction was present in 93 patients (33.9%), with a median LVEF of 46.9% (IQR 42.0, 50.5), median decrement in LVEF of 10.9% (IQR 5.5, 19.0), and median duration of persistence of 22 months (IQR 8.0, 57.3). There was no significant association with traditional operative nor cardiovascular risk variables. Patients with a reduced pre-operative LVEF were three times more likely to have worsened post-operative systolic function (OR=3.6, 95% CI=1.2-10.8, p=0.02), demonstrated more severe systolic impairment (LVEF <30%: OR 1.8, 95% CI=1.4-26.1, p=0.02), and exhibited persistent dysfunction (≥5 years: OR 1.6, 95% CI=1.8-14.6, p=0.002). Conclusions: Post-operative systolic dysfunction is common in patients with MFS following aortic root replacement surgery. A reduced pre-operative LVEF is associated with more severe and protracted post-operative impairment, and therefore may be an important consideration for surgical timing.

Abstract 15442: Pharmacological and Atrial Cardiomyocyte-Specific Inhibition of Tumor Necrosis Factor (TNF) Protects Against Adverse Atrial Remodeling and Valvular Atrial Fibrillation an a Mouse Model of Aortic Regurgitation

Introduction: Atrial fibrillation (AF) is the most common sustained supraventricular arrhythmia worldwide. Most conditions linked to AF, such as cardiovascular (CVD) and valvular disease, are linked to elevated atrial pressures and atrial cardiomyocyte (CM) stretch, which are powerful stimuli for atrial remodeling. We have shown that the proinflammatory and mechanosensitive cytokine tumor necrosis factor (TNF) is a key mediator of stretch-related atrial remodeling and AF. Hypothesis: As TNF is a critical factor mediating fibrosis, hypertrophy, inflammation, and arrhythmias in CVD, we hypothesized that targeting TNF-dependent signaling may offer a novel therapeutic target in AF patients. Methods: We created an aortic regurgitation (AR) mouse model of volume overload characterized by elevated left ventricular end diastolic (LVEDPs) and atrial pressures. To examine TNF-dependent AF pathogenesis in AR, the impact of Tnf excision in atrial CMs (Cre-recombinase expression controlled by an Nppa promoter) and pharmacological TNF inhibition with Etanercept (twice-weekly, 2.5 mg/kg) beginning 2-days (early) or 1-week (delayed) post-AR in CD1 mice were examined. Cardiac structural, functional, and electrophysiological properties were assessed using echo, pressure telemetry, immunohistochemistry, in vivo intracardiacs, and ex vivo optical mapping of AF. Results: Four weeks of AR resulted in chronically elevated LVEDPs and progressive LV dilatation, functional impairment, and hypertrophy in the absence of ventricular arrhythmias with or without TNF inhibition compared to SHAM mice. In atria, AR resulted in both in vivo (8/11, 73%) and ex vivo (5/8, 63%) AF inducibility, which was associated with hypertrophy, fibrosis, and macrophage infiltration (F4/80 + ) as well as decreased conduction velocity and atrial effective refractory periods. Importantly, atrial CM-specific Tnf excision (n=10) and both early (n=8) and delayed (n=6) pharmacological TNF inhibition attenuated AR-induced adverse atrial remodeling and protected against AF inducibility. Conclusions: AF pathogenesis and vulnerability with AR requires TNF, suggesting TNF is an important therapeutic target for the prevention and treatment of AF linked to elevated atrial pressures.

Abstract 15329: Heart Failure is an Adverse Risk Factor for Peri-Procedural Complications in Patients Undergoing Pulmonary Vein Isolation and Ablation for Atrial Fibrillation

Introduction: Percutaneous catheter ablation (PCA) for non-valvular atrial fibrillation (AF) is rapidly becoming commonplace for recently diagnosed paroxysmal AF. Heart failure (HF) and AF commonly coexist in patients. Elevated left ventricular and atrial pressures result in progressive left atrial dilation and remodeling which in turn predisposes to the generation of AF. Since many who undergo PCA for AF could have HF, we aimed to assess peri-procedural outcomes in this population. Methods: We utilized the National Inpatient Sample from 2016-2019 to identify 74,205 hospitalized adults who underwent PCA for AF. These hospitalizations were further stratified based on the presence of HF. A multivariate regression model was used to adjust for confounders and analyze the variables. Results: Of those who underwent PCA for AF, 33,435 (45%) had HF. In-hospital mortality was higher in those with HF (1.9% vs 1.14%; p=0.0001). Figure 1 shows the Forrest plot for multivariate analysis of peri-procedural complications when adjusted for patient demographics, co-morbidities, and hospital characteristics. When adjusted similarly, patients with HF who underwent PCA for AF had longer length of stay (LOS) by 1.5 days (p<0.001) and had additional hospital costs (HC) of $14,726 (p<0.001). Conclusions: In this study, patients undergoing Percutaneous catheter ablation (PCA) for AF with co-existing acute HF had significantly worse end points in terms of in-hospital mortality, LOS, HC, atrial flutter, AKI, sepsis, pneumonia, endotracheal intubation. One major limitation of our study is the lack of outpatient follow up. Although outcomes are worse in the acute setting of HF, there have been several studies such as CASTLE-AF, outlining that early ablation for AF in HF is associated with positive long-term effects including lower rates of death and hospitalization for HF. Despite unfavorable peri-procedural outcomes of HF in PCA, the long-term benefits should not be overlooked.

Abstract 11969: Effect of Aortic Valve Phenotype and Sex on Aortic Dilation: Results From the Progressa Study

Introduction: Bicuspid aortic valve (BAV) is frequently associated with aortic valve stenosis (AS) and concomitant aortopathy. However, few studies have evaluated the effect of aortic valve (AV) phenotype on the risk of progressive dilation of aorta dimensions. The aim of this study was to compare the progression rate of aorta dimensions according to AV phenotype (i.e. BAV vs tricuspid aortic valve [TAV]) and sex in patients with AS. Methods: Three-hundred twenty AS patients (231 TAV and 89 BAV; mean age: 64±14 years, 72% men) recruited in the PROGRESSA study (NCT01679431) were included in this analysis. Patients underwent Doppler-echocardiography annually to measure the AS hemodynamic severity and aorta dimensions including the aortic root (AR) at the sinus level and ascending aorta (AA) sections. The annualized change of echocardiographic parameters was assessed between baseline and last follow-up visit (median follow-up time: 4.01 [2.26 to 5.00] years). Results: Baseline AR diameters were similar between phenotypes and AA diameters were larger in BAV vs. TAV (34±5 vs. 34±4, p=0.43, 38±6 vs. 34±4, p<0.001, respectively). Median change in AR root diameter was similar in BAV vs. TAV (0.15 [-0.07 to 0.44] cm/year vs. 0.13 [-0.07 to 0.41] cm/year, p=0.69), whereas AA annualized change was larger in BAV (0.26 [0.02 to 0.52] cm/year vs. 0.14 [-0.06 to 0.40] cm/year, p=0.02). After multivariable adjustment, BAV phenotype was not a significant predictor of faster progression rate of AR or AA dilation (β: -0.003, p=0.98 and -0.095, p=0.25). In a separate analysis according to sex, the median changes in AR and AA were similar between women and men (p=0.53 and p=0.18). Predictors of AA progression rate in men were baseline AA diameter and AS severity (i.e. baseline peak aortic jet velocity) (all p≤0.03). In women, only higher low-density lipoprotein levels were significantly associated with faster AA progression (p=0.02). Regarding the AR annualized dilation, there were no significant predictors in both women and men (all p≥0.07). Conclusion: This study suggests that AV phenotype is not independently associated with faster dilation of the AR or AA in patients with established AS. However, the determinants of aorta dilation may be different between women and men.

Left Atrial Structural and Functional Response in Kidney Transplant Recipients Treated With Mesenchymal Stromal Cell Therapy and Early Tacrolimus Withdrawal

Autologous bone marrow-derived mesenchymal stromal cell (MSC) therapy and withdrawal of calcineurin inhibitors (CNIs) has been shown to improve systemic blood pressure control and left ventricular hypertrophy regression in kidney transplant recipients. In the current subanalysis, we aimed to evaluate the impact of this novel immunosuppressive regimen on the longitudinal changes of left atrial (LA) structure and function after kidney transplantation. Kidney transplant recipients randomized to MSC therapy-infused at weeks 6 and 7 after transplantation, with complete discontinuation at week 8 of tacrolimus (MSC group)-or standard tacrolimus dose (control group) were evaluated with transthoracic echocardiography at weeks 4 and 24 after kidney transplantation. The changes in echocardiographic parameters were compared between the randomization arms using an analysis of covariance model adjusted for baseline variable. Fifty-four participants (MSC therapy=27; tacrolimus therapy=27) were included. There was no significant interaction between the allocated treatment and the changes of indexed maximal LA volume (LAVImax) over the study period. Conversely, between 4 and 24weeks post-transplantation, an increase in indexed minimal LA volume (LAVImin) was observed in control subjects, while it remained unchanged in the MSC group, leading to a significant difference between groups (P=.021). Additionally, patients treated with MSC therapy showed a benefit in LA function, assessed by a significant interaction between changes in LA emptying fraction and LA reservoir strain and the randomization arm (P=.012 and P=.027, respectively). The combination of MSC therapy and CNIs withdrawal prevents progressive LA dilation and dysfunction in the first 6months after kidney transplantation. LAVImin and LA reservoir strain may be more sensitive markers of LA reverse remodeling, compared with LAVImax.

Role of the mitral valve in left ventricular assist device pathophysiology.

Functional mitral regurgitation (MR) in the setting of heart failure results from progressive dilatation of the left ventricle (LV) and mitral annulus. This leads to leaflet tethering with posterior displacement. Contrary to common assumptions, MR often does not resolve with LVAD decompression of the LV alone. The negative impact of significant (moderate-severe) mitral regurgitation in the LVAD setting is becoming better recognized in terms of its harmful effect on right heart function, pulmonary vascular resistance and hospital readmissions. However, controversies remain regarding the threshold for intervention and management. At present, there are no consensus indications for the repair of significant mitral regurgitation at the time of LVAD implantation due to the conflicting data regarding potential adverse effects of MR on clinical outcomes. In this review, we summarize the current understanding of MR pathophysiology in patients supported with LVAD and potential future management strategies.

Transjugular intrahepatic portosystemic shunt in portal hypertension: How to go further while staying on track?

Transjugular intrahepatic portosystemic shunt in portal hypertension: How to go further while staying on track?

Progressive and Simultaneous Right and Left Atrial Remodeling Uncovered by a Comprehensive Magnetic Resonance Assessment in Atrial Fibrillation.

Background Left atrial structural remodeling contributes to the arrhythmogenic substrate of atrial fibrillation (AF), but the role of the right atrium (RA) remains unknown. Our aims were to comprehensively characterize right atrial structural remodeling in AF and identify right atrial parameters predicting recurrences after ablation. Methods and Results A 3.0 T late gadolinium enhanced-cardiac magnetic resonance was obtained in 109 individuals (9 healthy volunteers, 100 patients with AF undergoing ablation). Right and left atrial volume, surface, and sphericity were quantified. Right atrial global and regional fibrosis burden was assessed with validated thresholds. Patients with AF were systematically followed after ablation for recurrences. Progressive right atrial dilation and an increase in sphericity were observed from healthy volunteers to patients with paroxysmal and persistent AF; fibrosis was similar among the groups. The correlation between parameters recapitulating right atrial remodeling was mild. Subsequently, remodeling in both atria was compared. The RA was larger than the left atrium (LA) in all groups. Fibrosis burden was higher in the LA than in the RA of patients with AF, whereas sphericity was higher in the LA of patients with persistent AF only. Fibrosis, volume, and surface of the RA and LA, but not sphericity, were strongly correlated. Tricuspid regurgitation predicted right atrial volume and shape, whereas diabetes was associated with right atrial fibrosis burden; sex and persistent AF also predicted right atrial volume. Fibrosis in the RA was mostly located in the inferior vena cava-RA junction. Only right atrial sphericity is significantly associated with AF recurrences after ablation (hazard ratio, 1.12 [95% CI, 1.01-1.25]). Conclusions AF progression associates with right atrial remodeling in parallel with the LA. Right atrial sphericity yields prognostic significance after ablation.

Effect of Vaginal pH on Efficacy of Prostaglandin Gel for Labour Induction

Background: Inducing Labour Is A Procedure Intended To Trigger Artificial Contractions Of The Uterus That GenerallyInvolve Progressive Erasure And Dilation Of The Cervix. This Will Hopefully Lead To The Birth Of A Baby Through TheVaginal Route.Objective: To Assess The Effect Of Vaginal Ph On Efficacy Of Prostaglandin Gel For Labour InductionMethods: A Total Of 200 Women With An Unfavourable Cervix Were Enrolled In This Retrospective Study. In Group I,There Were 100 Cases With Vaginal Ph Of ≤4.5 And In Group Ii, 100 Cases With Vaginal Ph Of > 4.5. Patients With MinimalChange In Bishop Score, Received Up To 3 Doses Of Prostaglandin Gel Intracervically, 6 Hours Apart. Women Who HadNo Change In Bishop Score At The End Of Induction With 3 Doses Of Prostaglandin Gel, Were Further Reassessed.Results: In Terms Of Maternal Age, Parity, Gestational Age, And Initial Bishop Score, There Was No Significant DifferenceBetween The Two Groups. Prior To Induction Of Labour, The Average Bishop Score Was 3.6±0.9 In Group I And 4±1.0 InGroup Ii. Out Of 200 Cases, 33% Cases Required Oxytocin Infusion In Group I And 13% In Group Ii.Conclusion: Parity Has A Major Impact On The Pre-Induction Of The Bishop Score And The Ph Itself Has A VaginalInfluence. Knowing The Pre-Induction Vaginal Ph May Also Be A Helpful Method For Determining The Outcome OfPge2 Induction.

Aortic flow patterns by 4D flow CMR in Marfan and Loeys-Dietz patients before and after valve sparing aortic root replacement: a comparison with healthy volunteers

Abstract Introduction Abnormal aortic flow patterns in patients with a connective tissue disorder (CTD), such as Marfan or Loeys-Dietz syndrome, may contribute to aortic root dilation [1,2]. Valve sparing aortic root replacement, which is effective in reducing the risk of aortic dissection in case of severe dilation, may also normalize flow patterns beyond the replaced aorta and potentially slow its progressive aortic dilation. Purpose To assess aortic flow dynamics in patients with a CTD by 4D flow cardiovascular magnetic resonance (CMR) before and after valve sparing aortic root replacement, and to compare the results with those of healthy volunteers (HV). Methods Patients with Marfan or Loeys-Dietz syndrome underwent two non-contrast enhanced 4D flow CMR, one before and another after undergoing valve sparing aortic root replacement. Healthy volunteers matched for age, sex and BSA were also included for comparison. Maximum velocity, in-plane rotational flow (IRF), systolic flow reversal ratio (SFRR) and wall shear stress (WSS) magnitude and its axial and circumferential components were obtained at 24 planes covering the thoracic aorta from the sinotubular junction to the descending aorta at the diaphragmatic level [3–5]. Results Sixteen patients and 21 healthy volunteers were included. Demographic and clinical data is presented in Table. The mean time between the CMR prior and posterior to surgery was 15 months. Compared to HV, patients with CTD before intervention presented lower maximum velocity at the proximal ascending aorta (Fig. 1A), lower IRF and circumferential WSS at the arch and the proximal descending aorta (Fig. 1B and F), lower magnitude and axial WSS at the proximal ascending and descending aorta (Fig. 1E and D), and increased SFRR at the proximal descending aorta (Fig. 1C). The intervention completely restored maximum velocity and partially-restored physiological helical flow and circumferential WSS, but barely improved axial WSS and SFRR. Conclusion Valve sparing aortic root replacement in patients with Marfan or Loeys-Dietz syndrome partially restore to physiological level both in-plane rotational flow and circumferential wall shear stress in the descending aorta. This flow normalization may contribute to prevent progressive dilation after the surgery. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Instituto de Salud Carlos III (Spain) (PI17/00381)Spanish Society of Cardiology (SEC/FEC-INV-CLI 20/015)

Mapping of thoracic aorta growth rate on serial self-navigated 3D whole-heart magnetic resonance angiographies by image registration

Abstract Introduction Accurate and reproducible assessment of aortic diameters and their growth rate is of key importance for the management of patients with thoracic aortic aneurysms [1,2]. It has been recently shown that image registration permits the assessment of progressive aortic dilation on ECG-gated contrast-enhanced CT angiography, outperforming manual quantification and allowing for 3D aortic size and growth mapping [3]. However, exposure to radiation makes it convenient to limit the use of CT for serial follow-up, especially in young patients. Self-navigated 3D whole-heart CMR acquisitions provides excellent image quality overcoming these limitations [4]. Purpose To evaluate the accuracy and reproducibility of registration-based assessment of aortic dilation using self-navigated 3D whole-heart CMR acquisitions. Methods Fifteen patients with two self-navigated 3D whole-heart CMR images obtained at least 1 year apart were included. Aortic root and thoracic aorta diameters were measured by 2 independent observers both manually (multiplanar reconstruction) and with the registration-based technique. To perform registration-based assessment, the aorta was semi-automatically segmented and typical anatomical landmarks were placed by each observer at baseline [3]. Geometrical mapping between baseline and follow-up acquisitions was obtained using deformable image registration, and applied to the baseline aortic surface points to obtain their location at follow-up. Finally, aortic diameters and their growth rate were automatically measured and used to calculated 3D aortic dilation maps. Agreement between techniques and their inter-observer reproducibility were calculated. Results Patients age was 27.2±14.5 years and 40% were male. Mean follow-up duration was 2.7±1.6 years. Compared to manual assessment, the registration-based technique presented low bias and excellent agreement for aortic diameters (Table 1), and low bias and moderate agreement for growth rates both in the aortic root and the thoracic aorta (Table, Fig. 1A). The techniques presented similar inter-observer reproducibility in the assessment of aortic diameters (Table 1), while the registration-based method demonstrated much higher inter-observer reproducibility in the assessment of growth rates in the aortic root and the thoracic aorta (Table 1, Fig. 1A and B). Three-dimensional mapping of thoracic aortic diameters and growth was highly reproducible (mean regional ICC=0.90 for diameters; 0.82 for growth rate). Conclusion The assessment of the dilation rate of the thoracic aorta via registration of serial self-navigated 3D whole-heart CMR acquisitions is accurate and reproducible in the aortic root and the thoracic aorta. Thus, it allows to assess local aortic growth without the drawbacks of CT. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Instituto de Salud Carlos III and Ministerio de Ciencia e Innovaciόn (Spain)

The impact of right ventricular size and function on long-term outcomes in patients undergoing cardiac resynchronization therapy

Abstract Background Right ventricular (RV) adverse remodelling is a complex process, consisting of progressive RV dilatation and RV systolic dysfunction. Both parameters individually are important prognostic markers in patients receiving cardiac resynchronization therapy (CRT). The prognostic value of assessing both parameters into one model has not been evaluated. Purpose The current study evaluated RV size and RV systolic function prior to CRT implantation and their association with outcome. Methods Patients who underwent CRT implantation and had echocardiographic data on RV size (assessed by indexed RV end-diastolic area [RVEDAi], using sex-specific cut-off values to define RV dilatation: RVEDAi >12.6 cm2/m2 for men and RVEDAi >11.5 cm2/m2 for women) and RV systolic function (measured by tricuspid annular plane systolic excursion [TAPSE], with TAPSE <17 mm considered RV dysfunction) before implantation, were included in the present analysis. The primary end-point was all-cause mortality. The incremental prognostic value of RV size and RV systolic function was assessed by likelihood-ratio testing evaluating the change in global chi-square values. Results A total of 773 patients (mean age 66±10 years, 75% males) were included in the current analysis, of which 509 patients (66%) had RV dilatation and/or dysfunction, with respectively 253 patients (33%) and 408 patients (53%) showing RV dilatation or RV systolic dysfunction. The cumulative survival rates for the overall population were 97%, 91% and 72% at 1-, 2- and 5-years, respectively. Five-year survival was significantly better in patients with normal RV size compared to patients with RV dilatation (log-rank p<0.001). Similarly, patients with normal RV systolic function had significantly better five-year survival, compared to patients with reduced RV systolic function (log-rank p<0.001). Multivariable Cox regression analysis for all-cause mortality showed that RV size and RV systolic function, assessed as continuous as well as categorical variables, were independently associated with all-cause mortality both individually and in combination (Figure 1). Larger RV size was associated with worse all-cause mortality, whereas better RV systolic function was associated with better all-cause mortality at 5-years follow-up. In addition, the evaluation of RV size plus RV function provided incremental prognostic value over the evaluation of RV size or RV function alone (likelihood-ratio test p<0.005 for all models; Figure 2). Conclusions Patients receiving CRT often present with RV dilatation and/or dysfunction, which are associated with significantly worse survival, compared to patients with normal RV size and function. Prognostic assessment in CRT recipients should include both RV size and function, since the combination of both parameters provides incremental prognostic value to assess all-cause mortality. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Society of Cardiology (ESC)

ANGIOTENSIN 1-7 EXERTS PROTECTIVE EFFECTS IN THORACIC AORTIC ANEURYSM BY ATTENUATING SMOOTH MUSCLE CELL PHENOTYPIC SWITCHING

ANGIOTENSIN 1-7 EXERTS PROTECTIVE EFFECTS IN THORACIC AORTIC ANEURYSM BY ATTENUATING SMOOTH MUSCLE CELL PHENOTYPIC SWITCHING

TARGETING TUMOR NECROSIS FACTOR (TNF) IN ATRIAL STRETCH-DEPENDENT ADVERSE ATRIAL REMODELING AND VALVULAR ATRIAL FIBRILLATION IN A MOUSE MODEL OF AORTIC REGURGITATION

TARGETING TUMOR NECROSIS FACTOR (TNF) IN ATRIAL STRETCH-DEPENDENT ADVERSE ATRIAL REMODELING AND VALVULAR ATRIAL FIBRILLATION IN A MOUSE MODEL OF AORTIC REGURGITATION

NADPH Oxidases in Aortic Aneurysms.

Abdominal aortic aneurysms (AAAs) are a progressive dilation of the infrarenal aorta and are characterized by inflammatory cell infiltration, smooth muscle cell migration and proliferation, and degradation of the extracellular matrix. Oxidative stress and the production of reactive oxygen species (ROS) have been shown to play roles in inflammatory cell infiltration, and smooth muscle cell migration and apoptosis in AAAs. In this review, we discuss the principles of nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase/NOX) signaling and activation. We also discuss the effects of some of the major mediators of NOX signaling in AAAs. Separately, we also discuss the influence of genetic or pharmacologic inhibitors of NADPH oxidases on experimental pre-clinical AAAs. Experimental evidence suggests that NADPH oxidases may be a promising future therapeutic target for developing pharmacologic treatment strategies for halting AAA progression or rupture prevention in the management of clinical AAAs.

Disparate biomechanical properties of the aorta in non‐aneurysmal and aneurysmal mice treated with angiotensin II

In vivo angiotensin II (AngII)‐treatment is a widely used experimental model to induce cardiovascular disease and results in a high likelihood of abdominal aorta aneurysm (AAA) formation. This involves progressive and irreversible focal dilation of the abdominal aorta and induces adverse aortic connective tissue remodeling contributing to aortic wall stiffening through inflammation, elastin degradation, and collagen restructuring. Hence, the present study aimed to investigate how AAA formation in AngII‐treated mice affects aortic function and biomechanics. To this end, C57Bl/6J mice were treated with AngII (1000 ng/[kg.min]) or PBS infusion for 28 days. Peripheral blood pressure, echocardiography, and aortic pulse wave velocity were measured in vivo. Thoracic aorta rings were studied ex vivo in organ chambers, while aortic vascular smooth muscle cell (VSMC) phenotype was investigated histologically. We confirmed peripheral hypertension, cardiac hypertrophy, aortic stiffening, and increased VSMC proliferation and migration after AngII‐treatment. Abdominal aorta aneurysm formation was observed in 8/13 AngII‐treated mice. Ex vivo thoracic aortic rings of both aneurysmal and non‐aneurysmal AngII‐treated mice showed high isobaric aortic stiffness, endothelial dysfunction, heightened α1‐adrenergic contractility, and altered VSMC contractile calcium signaling. However, aortic biomechanics were differently affected, with heightened α1‐adrenoreceptor mediated aortic stiffening in non‐aneurysmal mice, whereas contraction‐dependent stiffening was impaired in aneurysmal mice. In conclusion, although aneurysmal and non‐aneurysmal 4‐week AngII‐treated mice displayed similar changes in aortic physiology, aortic biomechanics were dissimilarly affected.

Left ventricular size and function in patients with systemic lupus erythematosus associate with lupus anticoagulant: An echocardiographic follow-up study

BackgroundSystemic lupus erythematosus (SLE) is a chronic autoimmune disease with increased risk of cardiac dysfunction. The pathophysiological mechanisms are poorly understood, and prognostic markers are warranted. PurposeWe aimed to identify SLE-characteristics associated with measures of cardiac size and function during a five-year follow-up. MethodsWe included 108 patients with SLE: 90% females, mean age 46 ± 13 years, median disease duration 14 (range 7–21) years. We performed blood sampling for potential biomarkers as well as a standard echocardiography at baseline and at a 5-year follow-up. To investigate associations with baseline and prospective 5-year changes in echocardiographic parameters, we performed multivariate regression analyses of SLE-related baseline variables (clinical disease activity, lupus nephritis, chronic kidney disease, anti-cardiolipin and/or anti-beta-2 glycoprotein I antibodies, and lupus anticoagulant (LAC)) and adjusted for traditional risk factors. ResultsDuring follow-up, diastolic function regressed in two out of five echocardiographic measures (E/A ratio 1.4 ± 0.5 vs. 1.3 ± 0.5, p = 0.002; tricuspid regurgitation peak velocity 2.0 ± 0.6 vs. 2.2 ± 0.4 mmHg, p < 0.001). Left ventricular (LV) end-diastolic volume index increased (43.7 ± 13.9 vs. 52.5 ± 15.7 mL/m2, p < 0.001). Left and right ventricular systolic function remained stationary. LAC was associated with inferior diastolic function: lower E/A ratio (p = 0.04) and higher E/e’ ratio at baseline (p = 0.04) and increased left ventricular atrial volume index during follow-up (p = 0.01). LAC was further associated with LV dilatation during follow-up (p = 0.01). ConclusionPresence of LAC was associated with measures of diastolic function as well as progressive LV dilatation during the 5-year follow-up. Thus, LAC might be a predictor of cardiac dysfunction in SLE patients. LAC is known to have implications for the microvascular circulation, but the clinical significance of the present findings is yet to be elucidated.

The association between cardiac magnetic resonance-derived aortic stiffness parameters and aortic dilation in young adults with bicuspid aortic valve: With and without coarctation of aorta

BackgroundBicuspid aortic valve (BAV) is associated with progressive aortic dilation. Studies in aortopathies have shown a correlation between increased aortic stiffness and aortic dilation. We aimed to evaluate aortic stiffness measures as predictors of progressive aortic dilation by cardiac magnetic resonance (CMR) in BAV patients. MethodsThis is a retrospective study of 49 patients with BAV (median age 21.1 years at first CMR visit) with ≥2 CMR at the Wisconsin Adult Congenital Heart Disease Program (WAtCH). Circumferential aortic strain, distensibility, and β-stiffness index were obtained from CMR-derived aortic root cine imaging, and aortic dimensions were measured at aortic root and ascending aorta. A linear mixed-model and logistic regression were used to identify important predictors of progressive aortic dilation. ResultsOver a median of 3.8 years follow-up, the annual growth rates of aortic root and ascending aorta dimensions were 0.25 and 0.16 mm/year, respectively. Aortic strain and distensibility decreased while β-stiffness index increased with age. Aortic root strain and distensibility were associated with progressive dilation of the ascending aorta. Baseline aortic root diameter was an independent predictor of >1 mm/year growth rate of the aortic root (adjusted OR 1.34, 95 % CI 1.03–1.74, p = 0.028). Most patients (61 %) had coexisting coarctation of aorta. Despite the higher prevalence of hypertension in patients with aortic coarctation, hypertension or coarctation had no effect on baseline aorta dimensions, stiffness, or progressive aortic dilation. ConclusionSome CMR-derived aortic stiffness parameters correlated with progressive aortic dilation in BAV and should be further investigated in larger and older BAV cohorts.

Myocardial fibrosis in asymptomatic patients undergoing surgery for mitral and aortic valve regurgitation.

Chronic heart valve regurgitation induces left ventricular (LV) volume overload, leading to the development of hypertrophy and progressive dilatation of the ventricle to maintain physiological cardiac output. In order to prevent potential irreversible LV structural changes, the identification of the best timing for treatment is pivotal. To assess the presence and extent of fibrosis in myocardial tissue in asymptomatic patients with valvular heart disease (VHD) and preserved LV dimensions and function undergoing cardiac surgery. Thirty-nine patients were enrolled. Sixteen patients were affected by aortic or mitral regurgitation: they were all asymptomatic, undergoing valve surgery according to VHD European Society of Cardiology guidelines. Twenty-three patients with end-stage nonischemic dilated cardiomyopathy (DCM) and severe LV dysfunction undergoing cardiac surgery for implantation of a durable left ventricular assist device (LVAD) served as controls. During surgery, VHD patients underwent three myocardial biopsies at the level of the septum, the lateral wall and LV apex, while in LVAD patients the coring of the apex of the LV was used. For both groups, the tissue samples were analyzed on one section corresponding to the apical area. All slides were stained with hematoxylin and eosin and Masson's trichrome staining and further digitalized. The degree of fibrosis was then calculated as a percentage of the total area. Of 39 patients, 23 met the inclusion criteria: 12 had mitral or aortic insufficiency with a preserved ejection fraction and 11 had idiopathic dilated cardiomyopathy. Quantitative analysis of apical sections revealed a myocardial fibrosis amount of 10 ± 6% in VHD patients, while in LVAD patients the mean apical myocardial fibrosis rate was 38 ± 9%. In VHD patients, fibrosis was also present in the lateral wall (9 ± 4%) and in the septum (9 ± 6%). Our case series study highlights the presence of tissue remodeling with fibrosis in asymptomatic patients with VHD and preserved LV function. According to our results, myocardial fibrosis is present at an early stage of the disease, well before developing detectable LV dysfunction and symptoms. Since the relationship between the progressive magnitude of myocardial fibrosis and potential prognostic implications are not yet defined, further studies on this topic are warranted.

Protein alterations in VSMCS reveal a defective repairment capacity in thoracic aortic aneurysm associated to BAV

Background and Aims : Thoracic aortic aneurysm (TAA) is caused by the progressive dilatation of the aortic wall. Its prevalence is significantly higher in subjects with bicuspid aortic valve (BAV) for unknown reasons. Considering that vascular smooth muscle cells (VSMCs) are essential for maintenance of the aortic wall structural integrity, we aimed to identify pathophysiological changes occurring in VSMCs from TAA subjects with BAV.