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Transcatheter tricuspid valve edge-to-edge repair (T-TEER) has been reported to be associated with right ventricular reverse remodeling (RVRR). Data on the temporal evolution of this phenomenon are scarce. The aim of this study was to evaluate RVRR over the course of 2-year follow-up after T-TEER using sequential 3-dimensional echocardiograms (3DE). The study included T-TEER patients with available 3DE at baseline and discharge. Further follow-ups were scheduled at 1 month, 6 months, as well as 1 and 2 years. The 3DE evaluation included right ventricular volumes (right ventricular end-diastolic volume [RVEDV3D]; right ventricular end-systolic volume [RVESV3D]), right ventricular ejection fraction (RVEF3D), and RV longitudinal strain of the free wall and the septum. The study included 231 patients (median age 82 [IQR: 79-86] years, 48% women). We observed a biphasic pattern of RVRR following T-TEER consisting of early RV volume unloading (phase 1, reduced RVEDV3D) and later structural remodeling (phase 2, reduced RVESV3D). Whereas RVEDV3D was significantly reduced early after the procedure (−9.7% from baseline to discharge; P < 0.001), RVESV3D remained unchanged at 1-month follow-up. Reduction in RVESV3D was observed at 6-month follow-up for the first time (−5.4% from baseline to 6-month follow-up; P < 0.001). Reduction in both RVEDV3D and RVESV3D peaked at 1-year follow-up and remained stable until 2 years after T-TEER. RV function declined early after T-TEER and gradually increased over the course of follow-up (RVEF3D at baseline 42.2% ± 8.9%, discharge 31.1% ± 9.4%, 2-year follow-up 41.6% ± 8.9%). The 3D RV longitudinal strain of the septum and 3D RV longitudinal strain of the free wall developed analogously. RVRR following T-TEER occurs in 2 stages and involves early RV unloading (reduction in RVEDV3D) and later structural RVRR (reduction in RVESV3D) with an improvement in RVEF. [Display omitted] [ABSTRACT FROM AUTHOR]

Obstructive hypertrophic cardiomyopathy (oHCM) is characterized by left ventricular (LV) hypertrophy, LV outflow tract obstruction, and left atrial dilation, which can be associated with progressive heart failure, atrial fibrillation, and stroke. Aficamten is a next-in-class cardiac myosin inhibitor that reduces outflow tract obstruction by modulating cardiac contractility, with the potential to reverse pathological remodeling and, in turn, reduce cardiovascular events. This study sought to investigate the effect of aficamten on cardiac remodeling compared with placebo using cardiovascular magnetic resonance (CMR) and its association with key clinical endpoints in the SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM) CMR substudy. SEQUOIA-HCM was a phase 3 double-blind, placebo-controlled trial for adults with symptomatic oHCM who were randomized 1:1 to 24 weeks of aficamten (dose range: 5-20 mg) or placebo. Eligible participants were offered enrollment in the CMR substudy with studies performed at baseline and week 24. Image analysis was performed in a blinded fashion by a core laboratory. Of the 282 randomized patients, 57 (20%) participated in the substudy, and of those, 50 (88%) completed both baseline and week 24 CMR. Baseline characteristics of the CMR cohort were similar to the overall study population. Of these 50 patients, 21 received aficamten and 29 received placebo. Relative to placebo, patients receiving aficamten demonstrated significant reductions (Δ least-squares mean) in LV mass index (−15 g/m2; 95% CI: −25 to −6 g/m2; P = 0.001), maximal LV wall thickness (−2.1 mm; 95% CI: −3.1 to −1.1 mm; P < 0.001), left atrial volume index (−13 mL/m2; 95% CI: −19 to −7 mL/m2; P < 0.001), native T1 relaxation time (−37 ms; 95% CI: −69 to −5 ms; P = 0.026), indexed extracellular volume fraction (−3.9 g/m2; 95% CI: −7.0 to −0.9 g/m2; P = 0.014), and indexed myocyte mass (−14 g/m2; 95% CI: −23 to −4 g/m2; P = 0.004), while there were no significant changes in LV chamber volumes, LV replacement fibrosis (late gadolinium enhancement mass −0.7 g; 95% CI: −2.9 to 1.6 g; P = 0.54), or extracellular volume (0.7%; 95% CI: −2.2% to 3.6%; P = 0.61). The CMR substudy of SEQUOIA-HCM demonstrated that treatment with aficamten relative to placebo for 24 weeks resulted in favorable cardiac remodeling. These changes, particularly with regard to LV mass, wall thickness, and left atrial size, could potentially lead to reduced cardiovascular events including heart failure and atrial fibrillation with longer follow-up. (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM [SEQUOIA-HCM]; NCT05186818) [ABSTRACT FROM AUTHOR]

There are significant sex and age differences in left ventricular (LV) remodeling that may lead to disparity in outcomes when used to inform the timing of aortic regurgitation (AR) intervention. The aim of this study was to examine whether left atrial (LA) parameters might represent better criteria than LV parameters to inform the timing of AR intervention. Using data on patients with moderate to severe or severe AR with serial echocardiography (2010-2016), the longitudinal trends in left atrial volume index (LAVI) and left atrial reservoir strain (LAr) were evaluated by sex and age. The incremental utility of these parameters in predicting adverse events over LV parameters was also determined. In 525 patients (25.7% women) with 1,687 echocardiograms over a median follow-up period of 2.0 years (Q1-Q3: 1.0-3.6 years), there was significant increase in LAVI (1.0 mL/m2 per year [95% CI: 0.76-1.2 mL/m2 per year]) and decrease in LAr (−1.3% per year [95% CI: −1.6% to −0.92%]), without a significant interaction by sex or age category (P for interaction ≥ 0.17). In addition, both LAVI and LAr were significant predictors of adverse events independent of LV parameters. The optimal discriminatory thresholds were 37 mL/m2 for LAVI and 35% for LAr. These thresholds were similar across categories of sex and age. Within the relatively short-term follow-up, surgery was associated with survival benefit among patients with LAVI ≥37 mL/m2 (HR: 0.33 [95% CI: 0.15-0.72]; P = 0.006) but was not statistically significant among patients with LAVI <37 mL/m2 (HR: 0.46 [95% CI: 0.18-1.17]; P = 0.09). Similarly, surgery was associated with survival for the subgroup with LAr ≤35% but not among those with LAr >35%. Unlike LV remodeling, LA remodeling demonstrates a similar rate of progression between categories of sex and age among patients with AR. In addition, LA parameters provide incremental prognostic value over LV parameters. [Display omitted] [ABSTRACT FROM AUTHOR]

Thoracic endovascular aortic repair (TEVAR) represents optimal therapy for complicated acute type B aortic dissection (aTBAD). Persistent knowledge gaps remain, including the optimal length of aortic coverage, impact on distal aortic remodeling, and fate of the dissected abdominal aorta. Review of the Emory Aortic Database identified 92 patients who underwent TEVAR for complicated aTBAD from 2012 to 2018. Standard TEVAR covered aortic zones 3 and 4 (from the left subclavian to the mid-descending thoracic aorta). Extended TEVAR fully covered aortic zones 3 though 5 (from the left subclavian to the celiac artery). Long-term imaging, clinical follow-up, and overall and aortic-specific mortality were reviewed. Extended TEVAR (n = 52) required a greater length of coverage vs standard TEVAR (n = 40) (240 ± 32 mm vs 183 ± 23 mm; P <.01). In-hospital mortality occurred in 5.4% of patients (7.7% vs 2.5%; P =.27) owing to mesenteric malperfusion (n = 3) or rupture (n = 2). The overall incidences of postoperative stroke, transient paraparesis, paraplegia, and dialysis were 5.4% (3.9% vs 7.5%; P =.38), 3.2% (5.8% vs 0%; P =.18), 0%, and 0% respectively, equivalent between groups. Follow-up was 96.6% complete to a mean of 6.1 years (interquartile range, 3.5-8.6 years). There were significantly higher rates of complete thrombosis or obliteration of the entire thoracic false lumen after Extended TEVAR (82.2% vs 51.5%; P =.04). Distal aortic reinterventions were less frequent after extended TEVAR (5.8% vs 20%; P =.04). Late aorta-specific survival was 98.1% after extended TEVAR vs 92.3% for standard TEVAR (P =.32). Extended TEVAR for complicated aTBAD is safe, results in a high rate of total thoracic false lumen thrombosis/obliteration, and reduces distal reinterventions. Longer-term follow-up will be needed to demonstrate a survival benefit compared to limited aortic coverage. [ABSTRACT FROM AUTHOR]

In patients with end-stage chronic obstructive pulmonary disease (COPD), severe pulmonary hypertension (PH) is frequently associated with less severe airway obstruction as compared to mild or no PH. However, the histologic correlate of this finding is not clear. We aimed to quantify remodeling of pulmonary arteries, airways, and parenchyma in random samples of explanted end-stage COPD lungs. We quantified remodeling of small pulmonary arteries, small airways, and the degree of emphysema (mean interseptal distance [MID]) with dedicated software. As primary objective, we compared COPD patients with severe PH (SevPH-COPD) with age- and sex-matched MildPH-COPD. For comparison, we also investigated COPD lungs with no PH (NoPH-COPD), idiopathic PAH (IPAH), and healthy donors. We included n = 17 SevPH-COPD (mPAP = 43 [39-45]mm Hg), n = 17 MildPH-COPD (mPAP = 28 [24-31]mm Hg), n = 5 NoPH-COPD (mPAP = 18 [16-19]mm Hg), n = 10 IPAH (mPAP = 72 [65-91]mm Hg), and n = 10 healthy donor lungs. SevPH-COPD versus MildPH-COPD was characterized by better preserved forced vital capacity (51% vs 40% predicted, p < 0.05), less emphysema (MID 169 µm vs 279 µm, p < 0.001), and less PAS-positive and CD45-positive mucosa cells (15% vs 22%, p = 0.063% and 5% vs 7%, p = 0.058) suggesting less airway inflammation. In COPD patients, intimal and medial thickening were strongly correlated with mPAP (r = 0.676, p < 0.001 and r = 0.595, p < 0.001). MID was negatively correlated with mPAP (r = −0.556, p < 0.001) and was highest in NoPH-COPD (mean 281 µm), suggesting that emphysema per se is not associated with PH. End-stage COPD with severe PH is characterized by pronounced pulmonary vascular remodeling, less inflammation of small airways, and less emphysema as compared to COPD with mild PH or no PH, suggesting that COPD with severe PH may represent a unique phenotype of COPD. [ABSTRACT FROM AUTHOR]

More than a hundred genetic loci have been associated with atrial fibrillation (AF). But the exact mechanism remains unclear and the treatment needs to be improved. This study aimed to investigate the mechanism and potential treatment of NPPA mutation–associated AF. Nppa knock-in (KI, p.I137T) rats were generated, and cardiac function was evaluated. Blood pressure was recorded using a tail-cuff system. The expression levels were measured using real-time polymerase chain reaction, enzyme-linked immunosorbent assay or Western blot analysis, and RNA-sequence analysis. Programmed electrical stimulation, patch clamp, and multielectrode array were used to record the electrophysical characteristics. Mutant rats displayed downregulated expression of atrial natriuretic peptide but elevated blood pressure and enlarged left atrial end-diastolic diameter. Further, gene topology analysis suggested that the majority of differently expressed genes in Nppa KI rats were related to inflammation, electrical remodeling, and structural remodeling. The expression levels of C-C chemokine ligand 5 and galectin-3 involved in remodeling were higher, while there were declined levels of Na v 1.5, Ca v 1.2, and connexin 40. AF was more easily induced in KI rats. Electrical remodeling included abbreviated action potentials, effective refractory period, increased late sodium current, and reduced calcium current, giving rise to conduction abnormalities. These electrophysiological changes could be reversed by the late sodium current blocker ranolazine and the Na v 1.8 blocker A-803467. Our findings suggest that structural remodeling related to inflammation and fibrosis and electrical remodeling involved in late sodium current underly the major effects of the Nppa (p.I137T) variant to induce AF, which can be attenuated by the late sodium current blocker and Na v 1.8 blocker. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] [ABSTRACT FROM AUTHOR]

Background: This study investigated the volumetric remodeling of the left liver after right hepatectomy looking for factors predicting the degree of hypertrophy and severe post-hepatectomy liver failure (PHLF). Methods: In a cohort of 121 right hepatectomies, we performed CT volumetrics study of the future left liver remnant (FLR) preoperatively and postoperatively. Factors influencing FLR degree of hypertrophy and severe PHLF were identified by multivariate analysis. Results: After right hepatectomy, the mean degree of hypertrophy and kinetic growth rate of the left liver remnant were 25% and 3%/day respectively. The mean liver volume recovery rate was 77%. Liver remodeling volume was distributed for 79% on segments 2 and 3 and 21% on the segment 4 (p<0.001). Women showed a greater hypertrophy of segments 2 and 3 compared with men (p=0.002). The degree of hypertrophy of segment 4 was lower in case of middle hepatic vein resection (p=0.004). Left liver remnant kinetic growth rate was associated with the standardized future liver remnant (sFLR) (p<0.001) and a two-stage hepatectomy (p=0.023). Severe PHLF were predicted by intraoperative transfusion (p=0.009), biliary tumors (p=0.013), and male gender (p=0.022). Conclusions: Volumetric remodeling of the left liver after right hepatectomy is not uniform and is mainly influenced by gender and sacrifice of middle hepatic vein. Male gender, intraoperative transfusion, and biliary tumors increase the risk of postoperative liver failure after right hepatectomy. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension (PHT) is a devastating disease with low survival rates. In PHT, chronic pressure overload leads to right ventricle (RV) stiffening; thus, impeding diastolic filling. Multiple mechanisms may contribute to RV stiffening, including wall thickening, microstructural disorganization, and myocardial stiffening. The relative importance of each mechanism is unclear. Our objective is to use a large animal model to untangle these mechanisms. Thus, we induced pulmonary arterial hypertension (PAH) in sheep via pulmonary artery banding. After eight weeks, the hearts underwent anatomic and diffusion tensor MRI to characterize wall thickening and microstructural disorganization. Additionally, myocardial samples underwent histological and gene expression analyses to quantify compositional changes and mechanical testing to quantify myocardial stiffening. Finally, we used finite element modeling to disentangle the relative importance of each stiffening mechanism. We found that the RVs of PAH animals thickened most at the base and the free wall and that PAH induced excessive collagen synthesis, increased cardiomyocyte cross-sectional area, and led to microstructural disorganization, consistent with increased expression of fibrotic genes. We also found that the myocardium itself stiffened significantly. Importantly, myocardial stiffening correlated significantly with collagen synthesis. Finally, our computational models predicted that myocardial stiffness contributes to RV stiffening significantly more than other mechanisms. Thus, myocardial stiffening may be the most important predictor for PAH progression. Given the correlation between myocardial stiffness and collagen synthesis, collagen-sensitive imaging modalities may be useful for estimating myocardial stiffness and predicting PAH outcomes. Ventricular stiffening is a significant contributor to pulmonary hypertension-induced right heart failure. However, the mechanisms that lead to ventricular stiffening are not fully understood. The novelty of our work lies in answering this question through the use of a large animal model in combination with spatially- and directionally sensitive experimental techniques. We find that myocardial stiffness is the primary mechanism that leads to ventricular stiffening. Clinically, this knowledge may be used to improve diagnostic, prognostic, and therapeutic strategies for patients with pulmonary hypertension. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] [ABSTRACT FROM AUTHOR]

Spiral artery remodeling is the process by which the uterine vessels become large bore low resistance conduits, allowing delivery of high volumes of maternal blood to the placenta to nourish the developing fetus. Failure of this process is associated with the pathophysiology of most of the major obstetric complications, including late miscarriage, fetal growth restriction and pre-eclampsia. However, the point at which remodeling 'fails' in these pathological pregnancies is not yet clear. Spiral artery remodeling has predominantly been described in terms of its morphological features, however we are starting to understand more about the cellular and molecular triggers of the different aspects of this process. This review will discuss the current state of knowledge of spiral artery remodeling, in particular the processes involved in loss of the vascular smooth muscle cells, and consider where in the process defects would lead to a pathological pregnancy. • Spiral artery remodeling is key for a successful pregnancy. • The morphological aspects of spiral artery remodeling are well described. • Understanding of the cellular and molecular mediators is becoming clearer. [ABSTRACT FROM AUTHOR]

Although several studies have demonstrated that mesenchymal stromal cells (MSCs) exhibit beneficial immunomodulatory properties in preclinical models of allergic asthma, effects on airway remodeling have been controversial. Recent evidence has shown that MSCs modify their in vivo immunomodulatory actions depending on the specific inflammatory environment encountered. Accordingly, we assessed whether the therapeutic properties of human mesenchymal stromal cells (hMSCs) could be potentiated by conditioning these cells with serum (hMSC-serum) obtained from patients with asthma and then transplanted in an experimental model of house dust mite (HDM)-induced allergic asthma. hMSC and hMSC-serum were administered intratracheally 24 h after the final HDM challenge. hMSC viability and inflammatory mediator production, lung mechanics and histology, bronchoalveolar lavage fluid (BALF) cellularity and biomarker levels, mitochondrial structure and function as well as macrophage polarization and phagocytic capacity were assessed. Serum preconditioning led to: (i) increased hMSC apoptosis and expression of transforming growth factor-β, interleukin (IL)-10, tumor necrosis factor-α–stimulated gene 6 protein and indoleamine 2,3-dioxygenase-1; (ii) fission and reduction of the intrinsic respiratory capacity of mitochondria; and (iii) polarization of macrophages to M2 phenotype, which may be associated with a greater percentage of hMSCs phagocytosed by macrophages. Compared with mice receiving hMSCs, administration of hMSC-serum led to further reduction of collagen fiber content, eotaxin levels, total and differential cellularity and increased IL-10 levels in BALF, improving lung mechanics. hMSC-serum promoted greater M2 macrophage polarization as well as macrophage phagocytosis, mainly of apoptotic hMSCs. Serum from patients with asthma led to a greater percentage of hMSCs phagocytosed by macrophages and triggered immunomodulatory responses, resulting in further reductions in both inflammation and remodeling compared with non-preconditioned hMSCs. [ABSTRACT FROM AUTHOR]

Genomewide association studies have associated >100 genetic loci with atrial fibrillation (AF), but establishing causal genes contributing to AF remains challenging. The purpose of this study was to determine candidate novel causal genes and mechanistic pathways associated with AF risk loci by incorporating gene expression and coexpression analyses and to provide a resource for functional studies and targeting of AF-associated genes. Cis-expression quantitative trait loci were identified for candidate genes near AF risk variants in human left atrial tissues. Coexpression partners were identified for each candidate gene. Weighted gene coexpression network analysis (WGCNA) identified modules and modules with overrepresentation of candidate AF genes. Ingenuity pathway analysis (IPA) was applied to the coexpression partners of each candidate gene. IPA and gene set over representation analysis were applied to each WGCNA module. One hundred sixty-six AF-risk single nucleotide polymorphisms were located in 135 loci. Eighty-one novel genes not previously annotated as putative AF risk genes were identified. IPA identified mitochondrial dysfunction, oxidative stress, epithelial adherens junction signaling, and sirtuin signaling as the most frequent significant pathways. WGCNA characterized 64 modules (candidate AF genes overrepresented in 8), represented by cell injury, death, stress, developmental, metabolic/mitochondrial, transcription/translation, and immune activation/inflammation regulatory pathways. Candidate gene coexpression analyses suggest significant roles for cellular stress and remodeling in AF, supporting a dual risk model for AF: Genetic susceptibility to AF may not manifest until later in life, when cellular stressors overwhelm adaptive responses. These analyses also provide a novel resource to guide functional studies on potential causal AF genes. [ABSTRACT FROM AUTHOR]

The collagen molecular family is the result of nearly one billion years of evolution. It is a unique family of proteins, the majority of which provide general mechanical support to biological tissues. Fibril forming collagens are the most abundant collagens in vertebrate animals and are generally found in positions that resist tensile loading. In animals, cells produce fibril-forming collagen molecules that self-assemble into larger structures known as collagen fibrils. Collagen fibrils are the fundamental, continuous, load-bearing elements in connective tissues, but are often further aggregated into larger load-bearing structures, fascicles in tendon, lamellae in cornea and in intervertebral disk. We know that failure to form fibrillar collagen is embryonic lethal, and excessive collagen formation/growth (fibrosis) or uncontrolled enzymatic remodeling (type II collagen: osteoarthritis) is pathological. Collagen is thus critical to vertebrate viability and instrumental in maintaining efficient mechanical structures. However, despite decades of research, our understanding of collagen matrix formation is not complete, and we know still less about the detailed mechanisms that drive collagen remodeling, growth, and pathology. In this perspective, we examine the known role of mechanical force on the formation and development of collagenous structure. We then discuss a mechanochemical mechanism that has the potential to unify our understanding of collagenous tissue assembly dynamics, which preferentially deposits and grows collagen fibrils directly in the path of mechanical force, where the energetics should be dissuasive and where collagen fibrils are most required. We term this mechanism: Mechanochemical force-structure causality. Our mechanochemical-force structure causality postulate suggests that collagen molecules are components of mechanochemically-sensitive and dynamically-responsive fibrils. Collagen molecules assemble preferentially in the path of applied strain, can be grown in place by mechanical extension, and are retained in the path of force through strain-stabilization. The mechanisms that drive this behavior operate at the level of the molecules themselves and are encoded into the structure of the biomaterial. The concept might change our understanding of structure formation, enhance our ability to treat injuries, and accelerate the development of therapeutics to prevent pathologies such as fibrosis. We suggest that collagen is a mechanochemically responsive dynamic element designed to provide a substantial "material assist" in the construction of adaptive carriers of mechanical signals. [Display omitted] [ABSTRACT FROM AUTHOR]

The benefit of an anterior mitral line (AML) in patients with persistent atrial fibrillation (AF) and anterior atrial scar undergoing ablation has never been investigated. The purpose of this study was to evaluate the outcomes of AML in addition to standard treatment compared to standard treatment alone (no AML) in this subset of patients. Patients with persistent AF and anterior low-voltage zone (LVZ) treated with AML in 3 centers were retrospectively enrolled. The patients were matched in 1:1 fashion with patients having persistent AF and anterior LVZ who underwent conventional ablation in the same centers. Matching parameters were age, LVZ burden, and repeated ablation. Primary endpoint was AF/atrial tachycardia (AT) recurrence. One hundred eight-six patients (age 66 ± 9 years; 34% women) were selected and divided into 2 matched groups. Bidirectional conduction block was achieved in 95% of AML. After median follow-up of 2 years, AF/AT recurrence occurred in 29% of the patients in the AML group vs 48% in the no AML group (log-rank P =.024). On Cox regression multivariate analysis, left atrial volume (hazard ratio [HR] 1.03; P =.006) and AML (HR 0.46; P =.003) were significantly associated with the primary endpoint. On univariate logistic regression, lower body mass index, older age, extensive anterior LVZ, and position of the left atrial activation breakthrough away from the AML were associated with first-pass AML block. In this retrospective matched analysis of patients with persistent AF and anterior scar, AML in addition to standard treatment was associated with improved AF/AT-free survival compared to standard treatment alone. [Display omitted] [ABSTRACT FROM AUTHOR]

Current guidelines for aortic regurgitation (AR) recommend the same linear left ventricular (LV) dimension for intervention regardless of age and sex. The purpose of this study was to evaluate the impact of age and sex on the degree of LV remodeling and outcomes. We included consecutive patients with severe AR who were serially monitored by echocardiogram between 2010 and 2016. The 2 main endpoints were as follows: 1) LV end-systolic volume indexed to body surface area (LVESVi) and LV end-diastolic volume indexed to body surface area; and 2) adverse events (AE). We evaluated the longitudinal rate of LV remodeling and determined the association between LV volume and AE by age and sex. A total of 525 adult patients (26% women) with a median echocardiogram follow-up of 2.0 years (IQR: 1.0-3.6 years) were included. At baseline, older patients (age ≥60 years) had smaller LV volumes compared with younger patients (age <60 years), eg, the mean LVESVi was 27.3 mL/m2 vs 32.3 mL/m2, respectively. Similarly, women had smaller LV volumes compared with men (mean LVESVi was 23.3 mL/m2 vs 32.4 mL/m2). On serial evaluation, older patients and women maintained smaller LV volumes compared with younger patients and men, respectively. There were 210 (40%) AE during follow-up. The optimal discriminatory threshold for AE varies by age and sex, eg, the LVESVi threshold was highest for young men (50 mL/m2), intermediate for older men (35 mL/m2), and lowest for women (27 mL/m2). On serial evaluation, older patients and women with chronic AR maintained smaller LV volumes than younger patients and men, respectively, and develop AE at lower LV volumes. [Display omitted] [ABSTRACT FROM AUTHOR]

To investigate the clinical effect of acupuncture among patients with dysphagia after cerebral infarction, and the nerve remodeling of acupuncture using diffusion tensor imaging. One hundred and twenty patients with dysphagia after cerebral infarction were randomly assigned to either acupuncture group or sham-acupuncture group with a 1:1 ratio. All patients received usual care and swallowing function training of neurology department. Additionally, acupuncture was applied at Sìshéncōng (四神聪EX-HN1), Băihuì (百会GV20), Tàiyáng (太阳EX-HN5), Fēngchí (风池GB20) and Shésānzhēn (舌三针three-tongue needling points, Extra) in acupuncture group. The needles were retained for 30 min each time, and five times a week for three weeks as a course of treatment. Two courses of treatments were required in total. In sham-acupuncture group, the blunt needles were put into the needle sleeve, and the top of needle was fixed on the skin. During treatment the blunt needle tip only had slight contact with the skin without any penetration. The blunt needle tips were placed on EX-HN1, GV20, EX-HN5, GB20 and three-tongue needling points, respectively. The duration of treatment in sham-acupuncture group was the same as that in acupuncture group. Before and after treatment, all patients underwent Kubota water swallowing test to evaluate the clinical effect. Using diffusion tensor image (DTI), the nerve remodeling was detected. Clinical effect: After treatment and assessed by water swallowing test, there were 38 cases of normal swallowing function in acupuncture group, higher than 15 cases in sham-acupuncture group (P < 0.05). Nerve remodeling: (1) apparent diffusion coefficient (ADC): before treatment, ADC in acupuncture group and sham acupuncture group were 1.76 ± 0.45 mm/s and 1.68 ± 0.51 mm/s, respectively. After treatment, ADC were 0.66 ± 0.15 mm/s and 0.74 ± 0.11 mm/s, respectively. The difference in ADC had no statistical significance between two groups after treatment (P > 0.05); (2) fractional anisotropy (FA): after treatment, FA of acupuncture group was 0.57 ± 0.06, which was significantly higher than that of sham-acupuncture group (P < 0.05); (3) observation of different infarct lesions: after treatment, ADC of temporal lobe infarction in acupuncture group was (0.57 ± 0.11) mm/s, lower than 0.82 ± 0.24 mm/s of sham acupuncture group, while FA in acupuncture group was 0.61 ± 0.07, higher than 0.45 ± 0.10 in sham-acupuncture group, both with statistical significance (both P < 0.05). Regarding the changes of FA maps for temporal lobe infarction before and after treatment, the transverse bundles of the white matter fibers increased remarkably in infarct lesions and on the healthy side of temporal lobe. Acupuncture could improve the swallowing function of patients with dysphagia after cerebral infarction. It reduced ADC and increased FA, especially among patients with temporal lobe infarction after treatment. Acupuncture may have a remodeling effect on transverse cortical fibers after temporal lobe infarction. [ABSTRACT FROM AUTHOR]

Due to the increasing incidence rate of obesity worldwide and the associated complications such as type 2 diabetes and cardiovascular diseases, research on the adipose tissue physiology and the role of the extracellular matrix (ECM) has gained tremendous attention. The ECM, one of the most crucial components in body tissues, undergoes remodeling and regeneration of its constituents to guarantee normal tissue function. There is a crosstalk between fat tissue and various body organs, including but not limited to the liver, heart, kidney, skeletal muscle, and so forth. These organs respond to fat tissue signals through changes in ECM, function, and their secretory products. Obesity can cause ECM remodeling, inflammation, fibrosis, insulin resistance, and disrupted metabolism in different organs. However, the mechanisms underlying the reciprocal communication between various organs during obesity are still not fully elucidated. Gaining a profound knowledge of ECM alterations during the progression of obesity will pave the way toward developing potential strategies to either circumvent pathological conditions or open an avenue to treat complications associated with obesity. [ABSTRACT FROM AUTHOR]

Background: Pacing at sites of longest interventricular delay has been associated with greater reverse remodeling in cardiac resynchronization therapy (CRT). However, the effects of pacing at such sites on clinical outcomes is less well studied.Objective: To assess the association between interventricular delay and clinical outcomes in CRT patients implanted with quadripolar left ventricular (LV) leads.Methods: RALLY-X4 was a registry study of the Acuity X4 quadripolar LV leads. Interventricular delay was measured during unpaced basal rhythm from the right ventricular (RV) lead to the LV lead electrode (E1 to E4) chosen for CRT pacing. Patients were stratified by median RV-LV delay (80 ms) into short and long delay groups, and they were also analysed by multivariable modelling. The primary composite outcome measure was all-cause mortality and heart failure hospitalization (HFH) at 18 months.Results: There were 581 patients with complete RV-LV delay data. The mean LV ejection fraction (EF) was 27% and 73% had a typical left bundle branch block. Predictors of long RV-LV delay included female sex, LBBB and QRS duration >150ms. Survival free of the primary outcome at 18 months follow up was 87% in the long activation delay group compared with 77% in the short delay group (p=0.0042). Multivariate analysis showed that RV-LV delay was a, independent predictor of survival free of HFH (p=0.028).Conclusions: Among CRT patients with quadripolar LV pacing leads, longer baseline interventricular activation delay was significantly associated with the composite endpoint of all-cause mortality and heart failure hospitalization. [ABSTRACT FROM AUTHOR]

Enlarged deep medullary veins (EDMVs) in patients with Sturge-Weber syndrome (SWS) may provide compensatory venous drainage for brain regions affected by the leptomeningeal venous malformation (LVM). We evaluated the prevalence, extent, hemispheric differences, and clinical correlates of EDMVs in SWS. Fifty children (median age: 4.5 years) with unilateral SWS underwent brain magnetic resonance imaging prospectively including susceptibility-weighted imaging (SWI); children aged 2.5 years or older also had a formal neurocognitive evaluation. The extent of EDMVs was assessed on SWI by using an EDMV hemispheric score, which was compared between patients with right and left SWS and correlated with clinical variables. EDMVs were present in 89% (24 of 27) of right and 78% (18 of 23) of left SWS brains. Extensive EDMVs (score >6) were more frequent in right (33%) than in left SWS (9%; P = 0.046) and commonly occurred in young children with right SWS. Patients with EDMV scores >4 had rare (less than monthly) seizures, whereas 35% (11 of 31) of patients with EDMV scores ≤4 had monthly or more frequent seizures (P = 0.003). In patients with right SWS and at least two LVM-affected lobes, higher EDMV scores were associated with higher intelligence quotient (P < 0.05). Enlarged deep medullary veins are common in unilateral SWS, but extensive EDMVs appear to develop more commonly and earlier in right hemispheric SWS. Deep venous remodeling may be a compensatory mechanism contributing to better clinical outcomes in some patients with SWS. [ABSTRACT FROM AUTHOR]

Background: Cardiac resynchronization therapy (CRT) response stratified by left ventricular (LV) remodeling revealed differing mortality profiles for distinct patient cohorts. Measuring functional endpoints, as well as mortality, may better assess CRT efficacy and inform patient management. However, the association between LV remodeling and functional outcomes after CRT is not well understood.Objective: To evaluate long-term CRT outcomes by extent of LV remodeling.Methods: REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction (NCT00271154) was a prospective, double-blind, randomized CRT trial. Patients were classified based on LV end-systolic volume (LVESV) change from baseline to 6-months post-CRT: Worsened (increase); Stabilized (0 to ≤15% reduction); Responder (>15 to < 30% reduction); and Super-responder (≥30% reduction). Subjects were evaluated annually for 5 years.Results: The analyses included 353 patients randomized to CRT-ON arm. All-cause mortality was higher in the worsened group compared with the 3 other response groups (29.8% vs 8.0%, p<0.0001), with no difference in survival among those groups (p=0.87). A significant interaction between LVESV group and time was observed for health status and quality of life (both p=0.02). The interaction was not significant for 6-minute hall walk (p=0.79); however, super-responders had increased walk distance compared to the 3 other response groups (p=0.03).Conclusion: Preventing further increase in LVESV with CRT was associated with reduced mortality, whereas functional measure improvement was associated with LV remodeling magnitude. These results support consideration of functional and mortality endpoints to assess CRT efficacy and provide further evidence the dichotomous 'responder and non-responder' classification should be modified. [ABSTRACT FROM AUTHOR]

A high body mass index (BMI) is often associated with metabolic syndrome, which is accompanied by systemic low-grade chronic inflammation. Here, we analyzed whether BMI, other components of metabolic syndrome, and/or inflammatory markers correlate with left ventricular geometry, function, and infarct size as assessed by serial cardiac magnetic resonance imaging (MRI) after a first (clinically evident) ST-elevation MI (STEMI). Within the Etiology, Titre-Course, and effect on Survival (ETiCS) study, cardiac MRI conducted 7–9 days and 12 months after MI enabled longitudinal characterization of patients with a first STEMI along with serial routine blood counts and multiplex cytokine measurements. Of 91 locally included STEMI patients, 47% were overweight (25 kg/m2 < BMI < 30 kg/m2) and 24% were obese (BMI ≥ 30 kg/m2). No patient died during 12 months of follow-up. Left ventricular ejection fraction (LVEF), measured 7–9 days after STEMI, was significantly lower in overweight (49.5 ± 7.1%) and obese (45.8 ± 12.0%) patients than in the normal weight group (56.2 ± 7.7%). Along with BMI (T = -3.8; p < 0.001), hemoglobin A1c (HbA1c; T = -3.1; p = 0.004) and peak C-reactive protein (T = -2.6; p = 0.013) emerged as independent predictors of worse LVEF 7–9 days post MI (R2 = 0.45). Only peak C-reactive protein (T = -4.4; p < 0.001), but not parameters of the metabolic syndrome, predicted worse LVEF 12 months after STEMI (R2 = 0.20). Both BMI and HbA1c correlated negatively with LVEF only early, but not late after STEMI. Peak CRP evolved as strongest predictor of cardiac function at all time points independent of the metabolic syndrome. • Body mass index and HbA1c correlate negatively with ejection fraction early after myocardial infarction • Peak C-reactive protein independently associates with lower ejection fraction at all time points • The differential role of inflammation needs to be investigated further via a preclinical approach [ABSTRACT FROM AUTHOR]

Early detection of Alzheimer's disease (AD) is essential for improving the patients outcomes and advancing our understanding of disease, allowing for timely intervention and treatment. However, accurate biomarkers are still lacking. Recent evidence indicates that hippocampal hyperexcitability precedes the diagnosis of AD decades ago, can predict cognitive decline. Thus, could hippocampal hyperactivity be a robust biomarker for early-AD, and what drives hippocampal hyperactivity in early-AD? these critical questions remain to be answered. Increasing clinical and experimental studies suggest that early hippocampal activation is closely associated with longitudinal β-amyloid (Aβ) accumulation, Aβ aggregates, in turn, enhances hippocampal activity. Therefore, in this narrative review, we discuss the role of Aβ-induced altered intrinsic neuronal properties as well as structural and functional remodeling of glutamatergic, GABAergic, cholinergic, noradrenergic, serotonergic circuits in hippocampal hyperactivity. In addition, we analyze the available therapies and trials that can potentially be used clinically to attenuate hippocampal hyperexcitability in AD. Overall, the present review sheds lights on the mechanism behind Aβ-induced hippocampal hyperactivity, and highlights that hippocampal hyperactivity could be a robust biomarker and therapeutic target in prodromal AD. • Aβ induced hippocampal hyperactivity in Alzheimer's patients and mouse models. • Altered intrinsic properties mediated Aβ-induced neuronal hyperactivity. • Aβ exacerbated hippocampal hyperactivity by remodeling hippocampus-connected neural networks. • Combined therapeutic approaches should be considered for prevention of Alzheimer's disease in prodromal stage. [ABSTRACT FROM AUTHOR]

This manuscript describes the mechanism by which supplementation with virgin coconut oil prevents the reduction of the relaxant reactivity of the trachea of guinea pigs with chronic allergic lung inflammation. [Display omitted] • Virgin coconut oil (VCO) improves impaired relaxation by asthma in rats. • VCO promotes formation of relaxing prostanoids or leukotrienes decrease. • VCO prevents negative modulation of β receptors/BKCa pathway by TGF-β. • VCO is a candidate for alternative therapy against allergic asthma. Asthma is a chronic inflammatory disease with many patients failing to respond appropriately to pharmacotherapy. Thus, virgin coconut oil (VCO) can be an alternative therapy. Guinea pigs were divided into control (Ctrl), chronic allergic lung inflammation (Asth), Asth treated with dexamethasone (Asth + dexa), and Asth supplemented with VCO (Asth + VCO4). The tested animals were sensitized and challenged with ovalbumin. Relaxation induced by arachidonic acid (AA) was impaired in Asth, and this reduction was prevented by VCO (p = 0.0004), indicating formation of relaxing prostanoids, or the decrease of cysteinyl-leukotrienes by VCO. Furthermore, a possible negative modulation of β receptors/BK Ca pathway by TGF–β in Asth was prevented by VCO (p = 0.0073). Finally, in Asth, Masson's trichrome staining revealed airway remodeling and immunohistochemistry showed increased TGF-β expression in the lungs of Asth (p < 0.0001)), which was prevented by VCO and dexamethasone (p < 0.0001), concluding VCO as a possible agent against asthma. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the osteolysis rate, graft remodeling, and risk factors for osteolysis at the 1-year threshold after an arthroscopic Latarjet procedure with double-button fixation. In this multicenter, retrospective study, postoperative computed tomography scans obtained after an arthroscopic Latarjet procedure with double-button fixation to treat anterior shoulder instability were analyzed at 15 days and at 3, 6, and 12 months. Graft volume, dimensions, and morphologic remodeling were analyzed. Twenty-seven patients were included (mean age, 26 years). At 1 year, osteolysis occurred in 19 of 27 patients (70%). The volume initially decreased until 6 months' follow-up (−35%; range, −75% to +26%) and then increased until our last follow-up. At 1 year, the graft volume decreased by 17% (range, −61% to +56%) compared with the immediate postoperative volume. In multivariate analysis, the rate of osteolysis was inversely associated with an unhealed graft at 3 months (P =.02; β coefficient = −44.50 [95% confidence interval, −81 to −8]). The maximal height of the graft significantly grew 0.2 cm (range, −55 to +124 mm) (P =.015). In the sagittal plane, osteolysis occurred in the superior part in 100% of patients (27 of 27) whereas bone formation occurred in the inferior part. In the axial plane, osteolysis occurred in the anterior part whereas bone formation occurred in the posterior part. In the articular part, the observed remodeling was aimed to obtain a new anatomic and congruent glenoid. At 1 year after an arthroscopic Latarjet procedure with double-button fixation, osteolysis occurred in 70% of patients. The rate of osteolysis was 17% of the initial volume. Osteolysis occurred mainly during the first 6 months, in the anterior and superior parts. Remodeling led to a circular anatomic glenoid. This osteolysis did not cause any recurrence of instability or require revision surgery. [ABSTRACT FROM AUTHOR]

The performance of small-diameter vascular grafts adapted to vascular replacement is commonly hindered by stenosis. To address this issue, a graft featuring rapid remodeling with degradation is warranted. In this work, a 1.8-mm-diameter graft was constructed by fabricating a decellularized human amniotic membrane (HAM) with polycaprolactone (PCL)/silk fibroin (SF) around it through electrospinning, namely, an HPS graft, and applied in a rat aortic grafting model for comparison to a decellularized porcine small intestinal submucosa (SIS)-integrated PCL/SF (SPS) graft and an autologous aorta. In vitro studies demonstrated that HAM provided a bioactive milieu for rapid endothelial cell proliferation and resisting fibroblast-induced collagen secretion. PCL/SF provides a biocompatible microenvironment for cellular infiltration with mechanical properties resembling those of the rat aorta. In vivo studies showed that the HPS graft induced functional endothelialization more rapidly, along with less intensive ECM deposition than the SPS graft upon the histologically weaker inflammatory response and foreign body reaction 4 weeks after implantation, and maintained patency by progressively stabilizing the remodeling structure approximating the native counterparts over 24 weeks. The bioengineered graft expands the applicability of allogeneic matrices with degradable electrospun polymers for long-term in situ vascular applications. An orchestrated remodeling of the vascular graft, featuring rapid endothelialization and resisting extracellular matrix (ECM) deposition on the luminal surface, with a mechanically stable structure, is requisite for long-term vascular patency. Nevertheless, off-the-shelf grafts might not fulfil the criteria under abdominal aortic pressure. Herein, we fabricated a 1.8-mm-diameter vascular graft through the integration of a decellularized human amniotic membrane (HAM) with electrospun polycaprolactone (PCL)/silk fibroin (SF). In a rat aortic grafting model, the graft is capable of rapid endothelialization and resisting collagen deposition and provides a native-like mechanical structure for stabilizing the remodeling process towards that of the native aorta. This bioengineered graft has potential for small-diameter vascular regeneration, and provides advanced strategies to facilitate full-remodeling tissue applications. [Display omitted] [ABSTRACT FROM AUTHOR]

• MFAP4 is a matrix protein promoting development and stability of elastic fibers. • MFAP4 is located predominantly at the elastin-microfibril interface in elastic tissues such as lung, blood vessels and skin. • During pathology, MFAP4 interaction with integrins leads to cell activation, inflammation and fibrosis. • MFAP4 shows potential as a diagnostic biomarker for liver fibrosis severity, while its usefulness in other diseases remains to be established. • We summarize and discuss the tissue distribution of MFAP4 and its reported role in health as well as various disease processes. Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein belonging to the fibrinogen-related domain family. It has been localized to elastic fiber-rich regions in several tissues including the arteries, lungs, heart and skin. MFAP4 binds collagen, fibrillins and tropoelastin and contributes to the process of microfibrillar assembly and maturation of elastic fibers. MFAP4 can also bind RGD-dependent integrins, predominantly α V β 3 and α V β 5 through its N-terminal RGD sequence, modulating cellular behavior. Circulating MFAP4 was suggested as a robust biomarker for hepatitis C virus- and alcoholic liver disease-related liver fibrosis, cardiovascular disorders and chronic obstructive pulmonary disease. In mice, MFAP4 seems to have a widely redundant role under homeostatic conditions, as global MFAP4 deficiency results in a mild pulmonary phenotype, causing emphysema-like airspace enlargement that progresses with age. However, emerging in vivo and in vitro data suggest that MFAP4 is actively involved in the pathogenesis of remodeling-associated diseases, including fibrosis, cardiovascular disorders, aging, asthma and cancer through activation of integrin-mediated signaling as well as by modulating TGF-β pathway, thus supporting maladaptive matrix remodeling. This review summarizes the current knowledge about MFAP4 structure and localization, its mechanisms of action in disease-induced tissue remodeling as well as its potential role as a clinical biomarker. [ABSTRACT FROM AUTHOR]

Background: Left ventricular diastolic dyssynchrony (LVDD), a dyssynchronous relaxation pattern, has been known to develop after myocardial damage. We aimed to evaluate the dynamic changes in LVDD in the early stage of acute myocardial infarction (AMI) by phase analysis of 99mtechnetium methoxyisobutylisonitrile (99mTc-MIBI) single-photon emission computed tomography (SPECT) gated myocardial perfusion imaging (GMPI) and explore its relationship with the progression of left ventricular remodeling (LVR). Methods: The left anterior descending coronary arteries of 16 Bama miniature swine were occluded with a balloon to build AMI models. Animals were imaged by SPECT GMPI before AMI and at 1 day, 1 week and 4 weeks after AMI, and quantitative analysis was performed to determine the extent of left ventricle (LV) perfusion defects, left ventricular systolic dyssynchrony (LVSD) and the LVDD parameters: phase histogram bandwidth (PBW) and phase standard deviation (PSD). Echocardiography was simultaneously applied to evaluate left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), and the LVDD parameters: Te-12-diff and Te-12-SD. Myocardial injury markers were measured, and 12-lead ECGs were performed. The degree of LVR progression was defined as ΔLVESV (%) = (LVESVAMI4weeks − LVESVAMI1day)/LVESVAMI1day. Results: Thirteen swine completed the study. LVDD parameters changed dynamically at different time points after AMI. LVDD occurred as early as 1 day after AMI, peaked at 1 week, and trended toward a partial recovery at 4 weeks. Phase analysis on SPECT GMPI showed a significant correlation with tissue Doppler imaging for the assessment of LVDD during the longitudinal evaluation (r = 0.569 to 0.787, both P <0.05). During the univariate and multivariate regression analyses, the LVDD parameters PBW and PSD as of 1 day after AMI were significantly associated with the progression of LVR, respectively (PBW, β = 0.004, 95% CI 0.001 to 0.007, P = 0.024; PSD, β = 0.008, 95% CI 0.000 to 0.017, P = 0.049). Adjusted smooth curve fitting and threshold effect analysis indicated PBW and PSD break-point values of 142° and 60.4°, respectively, to predict the progression of LVR after AMI. Conclusions: Phase analysis of SPECT GMPI can accurately and reliably characterize LVDD. LVDD occurred on the first day after AMI, reached its peak at 1 week, and partially recovered at 4 weeks after AMI. LVDD as evaluated by phase analysis of SPECT GMPI early after AMI was significantly associated with the progression of LVR. The early assessment of LVDD after AMI may provide helpful information for predicting the progression of LVR in the future. [ABSTRACT FROM AUTHOR]

• CVB3 inoculation of C57BL/6J mice induces acute self-limiting viral myocarditis. • Male sex is associated with higher mortality, cardiac inflammation and fibrosis. • A 10-fold increase of the virus inoculation dose does not impact viral myocarditis outcomes in male mice. • Tbet- and iNOS-reactive cells are the dominant inflammatory cells in the subacute phase. Viral infections are the leading cause of myocarditis. Besides acute cardiac complications, late-stage sequelae such as myocardial fibrosis may develop, importantly impacting the prognosis. Coxsackievirus B3 (CVB)-induced myocarditis in mice is the most commonly used translational model to study viral myocarditis and has provided the majority of our current understanding of the disease pathophysiology. Nevertheless, the late stages of disease, encompassing fibrogenesis and arrhythmogenesis, have been underappreciated in viral myocarditis research to date. The present study investigated the natural history of CVB-induced myocarditis in C57BL/6J mice, expanding the focus beyond the acute phase of disease. In addition, we studied the impact of sex and inoculation dose on the disease course. C57BL/6J mice (12 weeks old; n=154) received a single intraperitoneal injection with CVB to induce viral myocarditis, or vehicle (PBS) as control. Male mice (n=92) were injected with 5 × 105 (regular dose) (RD) or 5 × 106 (high dose) (HD) plaque-forming units of CVB, whereas female mice received the RD only. Animals were sacrificed 1, 2, 4, 8, and 11 weeks after CVB or PBS injection. Virally inoculated mice developed viral disease with a temporary decline in general condition and weight loss, which was less pronounced in female animals (P <.001). In male CVB mice, premature mortality occurred between days 8 and 23 after inoculation (RD: 21%, HD: 20%), whereas all female animals survived. Over the course of disease, cardiac inflammation progressively subsided, with faster resolution in female mice. There were no substantial group differences in the composition of the inflammatory cell infiltrates: predominance of cytotoxic T cells at day 7 and 14, and a switch from arginase1-reactive macrophages to iNOS-reactive macrophages from day 7 to 14 were the main findings. There was concomitant development and maturation of different patterns of myocardial fibrosis, with enhanced fibrogenesis in male mice. Virus was almost completely cleared from the heart by day 14. Serum biomarkers of cardiac damage and cardiac expression of remodeling genes were temporarily elevated during the acute phase of disease. Cardiac CTGF gene upregulation was less prolonged in female CVB animals. In vivo electrophysiology studies at weeks 8 and 11 demonstrated that under baseline conditions (i.e. in the absence of proarrhythmogenic drugs), ventricular arrhythmias could only be induced in CVB animals. The cumulative arrhythmia burden throughout the entire stimulation protocol was not significantly different between CVB and control groups. CVB inoculation in C57BL/6J mice represents a model of acute self-limiting viral myocarditis, with progression to different patterns of myocardial fibrosis. Sex, but not inoculation dose, seems to modulate the course of disease. [ABSTRACT FROM AUTHOR]

[Display omitted] • Normal wound healing progresses through homeostasis, inflammatory proliferative and remodeling phases. • Impaired wound healing in DFU is characterized by Hyperglycemia, Hypoxia, Bacterial infection, prolonged Inflammation and impaired Angiogenesis. • Collagen III is synthesized in the early stages of wound healing and is replaced by collagen I. • Collagen resolves inflammation, promote angiogenesis and tissue remodeling. • Collagen can be extracted from different sources and formulated into films, sponges, hydrogels, powders and nanofibers. Diabetic foot ulcer (DFU), a chronic wound with complex pathophysiology and immune cell imbalance is the major health concern as it takes longer healing time compared to normal wound healing. Collagen wound dressings have important role in DFU healing as these dressings improve angiogenesis, reduces inflammation time and aids in the regeneration of damaged tissue, maintains a moist wound environment by promoting optimal conditions for cell activity. These dressings are formulated with bovine, avian, porcine, marine, human based or recombinant sources such as plant based, insect based or microorganisms. Animal based biomaterials have concern of immunogenicity and purification while marine based and recombinant sources are better alternatives for these issues. Chemical modifications with other bioactive materials, reduces immunogenicity and the healing time, increase antioxidant activity, modulate inflammatory responses, improve wound microenvironment and promote broad spectrum antimicrobial property. Additionally, incorporation of mesenchymal stem cells and growth factors can generate various cells essential to wound healing, such as dermal fibroblasts (DFs), endothelial cells, and keratinocytes. This review summarizes the role of collagen wound dressing in DFU wound healing, to provide the conceptual understanding of the research and development of collagen as a potential biomaterial for diabetic wound healing. [ABSTRACT FROM AUTHOR]

To evaluate the cell proliferation and death, and structural morphology of the pancreatic islet cells of the rats with hyperglycemia in the first month of life and compare to those of the control rats. Female Sprague-Dawley newborn rats received Streptozotocin (a beta-cytotoxic drug) at birth for diabetes induction. Control and hyperglycemic animals were euthanized on different days of life: 5, 10, 15, and 30. The pancreas was collected and processed for immunohistochemical analysis of cleaved Caspase-3 (cell death), Ki-67 (cell proliferation), PDX-1 (transcription factor responsible for insulin synthesis), and endocrine hormones (insulin, glucagon, and somatostatin). Control females showed a higher percentage (%) of Ki-67-positive(+) cells on D10 and D15, a higher % of insulin+ and somatostatin+ cells on D15 and D30, a lower % of PDX-1+ cells on D10, and a higher % of glucagon+ cells on D10 and D30. Hyperglycemic females showed a lower % of Ki-67+ cells on D15, a higher % of cleaved Caspase-3+ cells on D15, and insulin+ cells on D15 and D30. In the comparison among the experimental groups, the hyperglycemic females showed an increased % of cleaved Caspase-3+ and Ki-67+ cells and a lower % of PDX-1+ cells. This study enabled a better understanding of the abnormal pancreas development regarding cellular proliferation, apoptosis, and hormonal synthesis in the neonatal period. Thus, the pancreatic islets of hyperglycemic rats do not reestablish the normal endocrine cell population, and cellular apoptosis overcame the proliferative activity of these cells. • This study made an integrative assessment of the pancreatic hormonal triad. • Hyperglycemic rats had impaired pancreatic β-cell maturation. • Apoptosis overcame the proliferative activity of islet cells in hyperglycemic rats. • Hyperglycemia impaired the reestablishment of the normal endocrine cell population. [ABSTRACT FROM AUTHOR]

Placental ischemia, resulting from inadequate remodeling of uterine spiral arteries, is a factor in the development of preeclampsia. However, the effect of endothelial progenitor cells that play a role in the vascular injury-repair program is largely unexplored during remodeling. Here, we observe that preeclampsia-afflicted uterine spiral arteries transition to a synthetic phenotype in vascular smooth muscle cells and characterize the regulatory axis in endothelial progenitor cells during remodeling in human decidua basalis. Excessive sEng, secreted by AMP-activated protein kinase (AMPK)-deficient endothelial progenitor cells through the inhibition of HO-1, damages residual endothelium and leads to the accumulation of extracellular matrix produced by vascular smooth muscle cells during remodeling, which is further confirmed by animal models. Collectively, our findings suggest that the impaired functionality of endothelial progenitor cells contributes to the narrowing of remodeled uterine spiral arteries, leading to reduced utero-placental perfusion. This mechanism holds promise in elucidating the pathogenesis of preeclampsia. [Display omitted] • Endothelial progenitor cells control uterine spiral artery (uSpA) remodeling • CD117highKDRhigh cells with AMPK deficiency release excessive sEng via HO-1 inhibition • Excessive sEng induces stenosis in remodeled uSpAs Tan et al. demonstrate that the suppressive AMPK/HO-1 regulatory axis in endothelial progenitor cells overproduces sEng, which contributes to the narrowing of remodeled uterine spiral arteries. The mechanism holds promise in elucidating the pathogenesis of preeclampsia. [ABSTRACT FROM AUTHOR]

• Cardiac fibrosis continues to play an important role in driving adverse clinical outcomes for a growing number of patients worldwide. • Various cellular and molecular pathways have been implicated in the pathogenesis of cardiac fibrosis. • Recent work has revealed that the local immune microenvironment may have a critical role underlying the progression of cardiac fibrosis. • Stem cell therapy for treating cardiac fibrosis has been fraught with challenges, but ongoing studies suggest a more precise approach may have benefits in blunting the progression of fibrotic processes in the heart. Cardiac fibrosis is a significant contributor to heart failure, a condition that continues to affect a growing number of patients worldwide. Various cardiovascular comorbidities can exacerbate cardiac fibrosis. While fibroblasts are believed to be the primary cell type underlying fibrosis, recent and emerging data suggest that other cell types can also potentiate or expedite fibrotic processes. Over the past few decades, clinicians have developed therapeutics that can blunt the development and progression of cardiac fibrosis. While these strategies have yielded positive results, overall clinical outcomes for patients suffering from heart failure continue to be dire. Herein, we overview the molecular and cellular mechanisms underlying cardiac tissue fibrosis. To do so, we establish the known mechanisms that drive fibrosis in the heart, outline the diagnostic tools available, and summarize the treatment options used in contemporary clinical practice. Finally, we underscore the critical role the immune microenvironment plays in the pathogenesis of cardiac fibrosis. [ABSTRACT FROM AUTHOR]

Bioengineering an effective, small diameter (<6 mm) artificial vascular graft for use in bypass surgery when autologous grafts are unavailable remains a persistent challenge. Commercially available grafts are typically made from plastics, which have high strength but lack elasticity and present a foreign surface that triggers undesirable biological responses. Tissue engineered grafts, leveraging decellularized animal vessels or derived de novo from long-term cell culture, have dominated recent research, but failed to meet clinical expectations. More effective constructs that are readily translatable are urgently needed. Recent advances in natural materials have made the production of robust acellular conduits feasible and their use increasingly attractive. Here, we identify a subset of natural materials with potential to generate durable, small diameter vascular grafts. Commercial synthetic vascular grafts are made from strong, stiff, chemically inert polymers. The properties of these materials are unsuited to the human vasculature, leading them to rapidly fail in low diameter (<6 mm) applications. Natural biomaterials have inherent advantages that make them good candidates for incorporation into the next generation of grafts, including enhanced biological signaling and tunable mechanical properties. Classical barriers to the wider adoption of natural materials include inadequate strength for vascular applications, rapid degradation, overly complex designs, and difficulty in translation out of a lab setting. Advances in manufacturing, material source, and postprocessing have renewed the promise of natural materials, including silk, collagen, elastin, chitosan, and cellulose, to meet the challenges of developing effective artificial small diameter grafts. [ABSTRACT FROM AUTHOR]

This study was designed to observe the changes in the carotid canal over time by measuring the carotid canal diameter longitudinally in adult patients with moyamoya disease in whom disease stage progressed spontaneously. Of 70 adult patients with moyamoya disease, 10 adult patients on 15 sides with spontaneous progression of the disease stage during conservative follow-up were included in this study. Another 10 moyamoya cases on 15 sides were selected as the controls without disease progression. All patients were followed up for at least 60 months after the progression of disease stage was confirmed. In addition, 5 patients who underwent microvascular decompression were included as healthy controls. The carotid canal diameter was measured with bone window computed tomography (CT) and source images of time-of-flight magnetic resonance angiography at initial presentation, and then were serially monitored with the latter. There was a significant correlation between the values obtained from CT and magnetic resonance imaging (R2 = 0.992, P < 0.001). The carotid canal diameter in moyamoya disease at initial presentation was 4.29 ± 0.61 mm, being smaller than 5.20 ± 0.51 mm in healthy controls (P < 0.01). In response to disease progression, the carotid canal diameter started to decrease at 6 months after disease progression was confirmed, and reduced to about 85% of the original level during 60 months (P < 0.01). The phenomenon was not observed in patients without disease progression. The carotid canal diameter can decrease in response to disease progression even in adult moyamoya disease. "Negative" bone remodeling may play a key role in this unique phenomenon. [ABSTRACT FROM AUTHOR]

Background: Despite interest in left ventricular (LV) recovery, there is an absence of data on the relationship between intrinsic LV hemodynamics and both reverse remodeling on a continuous flow LV assist device (CF-LVAD) therapy. We hypothesized that the markers of intrinsic LV function would be associated with remodeling, optimization, and outcomes.Methods and Results: Patients with continuous flow LVADs between 2015 and 2019 who underwent combined left and right heart catheterization ramp protocol at a single institution were enrolled. Patients were stratified by response to continuous flow LV assist device therapy: full responders, partial responders, or nonresponders per the Utah-Inova criteria. Hemodynamic data, including LV hemodynamics of peak LV dP/dt and tau (τ) were obtained at each phase. The 1-year heart failure hospitalization-free survival was the primary end point. Among 61 patients included in the current study 38 (62%) were classified as nonresponders, 14 as partial responders (23%), and 9 as full responders (15%). The baseline LV dP/dt and τ varied by response status (P ≤ .02) and generally correlated with reverse remodeling on linear regression. Biventricular filling pressures varied with τ and there was an interaction effect of speed on the relationship between τ and pulmonary capillary wedge pressure (P = .04). Last, τ was a prognostic marker and associated with 1-year HF hospital-free survival (odds ratio 1.04, 95% confidence interval 1.00-1.07, P = .02 per millisecond increase).Conclusions: Significant correlations between τ and LV dP/dt and reverse remodeling were noted, with τ serving as a prognostic marker. A higher LVAD speed was associated with a greater reliance on LVAD for unloading. Future work should focus on defining the optimal level of LVAD support in relation to LV recovery. [ABSTRACT FROM AUTHOR]

Background: Cardiac resynchronization therapy (CRT) reduces mortality and improves outcomes in appropriately selected patients with heart failure (HF); however, response may vary.Objective: We sought to correlate 6-month CRT response assessed by clinical composite score (CCS) and left ventricular end-systolic volume index (LVESVi) with longer-term mortality and HF-related hospitalizations.Methods: Individual patient data from 5 prospective CRT studies-Multicenter InSync Randomized Clinical Evaluation (MIRACLE), Multicenter InSync ICD Randomized Clinical Evaluation (MIRACLE ICD), InSync III Marquis, predictors of response to cardiac resynchronization therapy (PROSPECT), and Adaptive CRT-were pooled. Classification of CRT response status using CCS and LVESVi were made at 6 months. Kaplan-Meier analyses were used to assess time to mortality. Cox proportional hazards regression models were used to compute hazard ratios (HRs) for the 3 levels of CRT response: improved, stabilized, and worsened. Adjusted models controlled for baseline factors known to influence both CRT response and mortality. HF-related hospitalization was compared between CRT response categories using incidence rate ratios.Results: Among a total of 1603 patients, 1426 and 1165 were evaluated in the CCS and LVESVi outcome assessments, respectively. Mortality was significantly lower for patients in the improved (CCS: HR 0.22; 95% confidence interval [CI] 0.15-0.31; LVESVi: HR 0.40; 95% CI 0.27-0.60) and stabilized (CCS: HR 0.38; 95% CI 0.24-0.61; LVESVi: HR 0.41; 95% CI 0.25-0.68) groups than in the worsened group for both measures after adjusting for potential confounders.Conclusion: Patients with a worsened CRT response status have a high mortality rate and HF-related hospitalizations. Stabilized patients have a more favorable prognosis than do worsened patients and thus should not be considered CRT nonresponders. [ABSTRACT FROM AUTHOR]

Brain arteriovenous malformations (AVMs) are characterized by a high-pressure, low-resistance vascular nidus created by direct shunting of blood from feeding arteries into arterialized veins, bypassing intervening capillaries. AVMs pose a risk of spontaneous rupture because the vessel walls are continuously exposed to increased shear stress and abnormal flow phenomena, which lead to vessel wall inflammation and distinct morphologic changes. The annual rupture rate is estimated at 2%, and once an AVM ruptures, the risk of rerupture increases 5-fold. The ability of AVMs to grow, regress, recur, and undergo remodeling shows their dynamic nature. Identifying the underlying cellular and molecular pathways of AVMs not only helps us understand their natural physiology but also allows us to directly block vital pathways, thus preventing AVM development and progression. Management of AVMs is challenging and often necessitates a multidisciplinary approach, including neurosurgical, endovascular, and radiosurgical expertise. Because many of these procedures are invasive, carry a risk of inciting hemorrhage, or are controversial, the demand for pharmacologic treatment options is increasing. In this review, we introduce novel findings of cellular and molecular AVM physiology and highlight key signaling mediators that are potential targets for AVM treatment. Furthermore, we give an overview of syndromes associated with hereditary and nonhereditary AVM formation and discuss causative genetic alterations. [ABSTRACT FROM AUTHOR]

Objectives: Excessive left ventricular mass (LVM) results in inefficient LV work with energy waste leading to a negative prognostic effect. We aimed at investigating the presence of inappropriate LVM and calculating the myocardial mechano-energetic efficiency index (MEEi) in former pre-eclamptic (PE) women (with or without HELLP syndrome) compared to women who experienced HELLP syndrome without PE.Study Design: In this cross-sectional study, women with a history of normotensive HELLP (n = 32), PE without HELLP (n = 59), and PE with HELLP (n = 101) underwent echocardiography as part of the clinical CV work-up after their complicated pregnancies from 6 months to 4 years postpartum. We excluded women with comorbidities, including chronic hypertension, hypercholesterolemia, and obesity.Main Outcome Measures: LVM excess was calculated as the ratio between observed LVM and predicted LVM (by sex, stroke work and height), while MEEi was considered as the ratio between stroke work and "double product" (to approximate energy consumption), indexed to LVM.Results: LV hypertrophy was present in 8-14% and concentric remodeling in 31-42% of women, without intergroup difference. LVM was inappropriate in one-third of normotensive former HELLP and in about one-half of PE with or without HELLP, with no difference among groups. Accordingly, without nominal difference, MEEi showed a tendency towards lower values in former pre-eclamptic individuals.Conclusions: Women with a history of HELLP syndrome, independently from the presence/absence of PE, showed inappropriate LVM in the first 4 years after delivery, which may partially explain the elevated CV risk in these women compared to the general female population. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to determine the most appropriate timing for thoracic endovascular aortic repair (TEVAR) of type B aortic dissection (TBAD) in terms of remodeling of the aorta. A total of 41 patients who had undergone TEVAR for the treatment of aortic dissection were included in the present study. The patients were divided into two groups: those who had undergone TEVAR in the acute or subacute phase (group A) and those who had undergone TEVAR in the chronic phase (group B). The indications for TEVAR as the treatment of TBAD were the presence of aortic rupture or malperfusion of the aortic branches, a maximum aortic diameter of ≥40 mm on the initial diagnostic computed tomography scan, and/or expansion of the aorta of ≥5 mm within 3 months for acute and subacute TBAD. The indication was a maximum aortic diameter of ≥50 mm or expansion of the aorta of ≥5 mm within 1 year for chronic TBAD. The diameters of the aorta, true lumen, and false lumen were measured at the level of the most dilated part of the descending aorta (level M) and at the diaphragm (level D) on the computed tomography scan obtained before TEVAR and at the 2-year follow-up examination. The median interval between TEVAR and the onset of TBAD was 0.2 month (interquartile range, 0.03-0.7 month) in group A (n = 21) and 32 months (interquartile range, 4.7-35.2 months) in group B (n = 20). Except for the aortic diameter at level D in group B, favorable remodeling was obtained at both levels in both groups. The diameter change ratio of the aorta at level D was significantly greater in group A than in group B (P =.02). Receiver operating characteristic curve analysis of the interval for a significant decrease in the aortic diameter at level D yielded 4.2 months as the optimal threshold for performing TEVAR (area under the curve, 0.859; 95% confidence interval, 0.7-1.0). TEVAR for TBAD will result in favorable outcomes, irrespective of the timing of the procedure. However, it might be more effective to perform TEVAR within 4.2 months of the onset of TBAD, provided that the TEVAR procedure can be performed safely. [ABSTRACT FROM AUTHOR]

Background: Electrophysiological (EP) properties have been studied mainly in the monocrotaline model of pulmonary arterial hypertension (PAH). Findings are confounded by major extrapulmonary toxicities, which preclude the ability to draw definitive conclusions regarding the role of PAH per se in EP remodeling.Objective: The purpose of this study was to investigate the EP substrate and arrhythmic vulnerability of a new model of PAH that avoids extracardiopulmonary toxicities.Methods: Sprague-Dawley rats underwent left pneumonectomy (Pn) followed by injection of the vascular endothelial growth factor inhibitor Sugen-5416 (Su/Pn). Five weeks later, cardiac magnetic resonance imaging was performed in vivo, optical action potential (AP) mapping ex vivo, and molecular analyses in vitro.Results: Su/Pn rats exhibited right ventricular (RV) hypertrophy and were highly prone to pacing-induced ventricular tachycardia/fibrillation (VT/VF). Underlying this susceptibility was disproportionate RV-sided prolongation of AP duration, which promoted formation of right-sided AP alternans at physiological rates. While propagation was impaired at all rates in Su/Pn rats, the extent of conduction slowing was most severe immediately before the emergence of interventricular lines of block and onset of VT/VF. Measurement of the cardiac wavelength revealed a decrease in Su/Pn relative to control. Nav1.5 and total connexin 43 expression was not altered, while connexin 43 phosphorylation was decreased in PAH. Col1a1 and Col3a1 transcripts were upregulated coinciding with myocardial fibrosis. Once generated, VT/VF was sustained by multiple reentrant circuits with a lower frequency of RV activation due to wavebreak formation.Conclusion: In this pure model of PAH, we document RV-predominant remodeling that promotes multiwavelet reentry underlying VT. The Su/Pn model represents a severe form of PAH that allows the study of EP properties without the confounding influence of extrapulmonary toxicity. [ABSTRACT FROM AUTHOR]

Progressive displacement of diaphyseal clavicle fractures has been observed in adult patients, at times necessitating a change from nonoperative to operative treatment. Whether this occurs in adolescent patients has not been well investigated. The purpose of this study was to assess the rate and extent of progressive clavicle fracture displacement in adolescent patients following injury and during the early stages of healing. This was a multicenter study evaluating prospective data that had previously been collected as part of a larger study evaluating the functional outcomes of adolescent clavicle fractures. A consecutive series of completely displaced diaphyseal clavicle fractures in patients aged 10-18 years treated at 1 of 3 tertiary-care pediatric trauma centers was included; all fractures underwent standardized imaging within 2 weeks of the date of injury and during the course of healing (5-20 weeks after injury). Measurements of clavicle shortening, superior displacement, and angulation were performed using validated techniques. Progressive displacement and/or interval improvement in fracture alignment, as well as the subsequent need for surgical intervention, was noted. Patient demographic and radiographic parameters were assessed as possible risk factors for interval displacement. One hundred patients met the inclusion criteria. Mean end-to-end shortening, cortex-to-cortex shortening, superior displacement, and angulation at the time of injury were 24 mm, 15 mm, 15 mm, and 7°, respectively. At a mean of 10 weeks after injury, the fracture alignment improved across all 4 measurements for the overall cohort, with mean improvements of 3.5 mm in end-to-end shortening, 3.3 mm in cortex-to-cortex shortening, 2.1 mm in superior displacement, and 2° in angulation. By use of a clinical threshold of a change in shortening or displacement of 10 mm or change in angulation of 10°, 26% of fractures improved, 4% worsened, and 70% remain unchanged. Patients with more severe fractures were more likely to have improved alignment than were patients with less displaced fractures (P <.001). No patient underwent surgical intervention for progressive displacement. Significant early improvements in fracture alignment were observed in a substantial percentage of adolescent patients with completely displaced clavicle fractures. Among the most severely displaced fractures, shortening improved approximately 6 mm and angulation improved approximately 9°. In 4% of cases, increased displacement was observed, but this tended to be mild, and in no cases did it prompt surgical intervention. This finding indicates that the true final deformity after an adolescent clavicle fracture is commonly less than that present at the time of injury. [ABSTRACT FROM AUTHOR]

Aim: Muscular dystrophy (MD) is a progressive disease with predominantly muscular symptoms. Myotonic dystrophy type II (MD2) and facioscapulohumeral muscular dystrophy type 1 (FSHD1) are gaining an increasing awareness, but data on cardiac involvement are conflicting. The aim of this study was to determine a progression of cardiac remodeling in both entities by applying cardiovascular magnetic resonance (CMR) and evaluate its potential relation to arrhythmias as well as to conduction abnormalities. Methods and results: 83 MD2 and FSHD1 patients were followed. The participation was 87% in MD2 and 80% in FSHD1. 1.5 T CMR was performed to assess functional parameters as well as myocardial tissue characterization applying T1 and T2 mapping, fat/water-separated imaging and late gadolinium enhancement. Focal fibrosis was detected in 23% of MD2) and 33% of FSHD1 subjects and fat infiltration in 32% of MD2 and 28% of FSHD1 subjects, respectively. The incidence of all focal findings was higher at follow-up. T2 decreased, whereas native T1 remained stable. Global extracellular volume fraction (ECV) decreased similarly to the fibrosis volume while the total cell volume remained unchanged. All patients with focal fibrosis showed a significant increase in left ventricular (LV) and right ventricular (RV) volumes. An increase of arrhythmic events was observed. All patients with ventricular arrhythmias had focal myocardial changes and an increased volume of both ventricles (LV end-diastolic volume (EDV) p = 0.003, RVEDV p = 0.031). Patients with supraventricular tachycardias had a significantly higher left atrial volume (p = 0.047). Conclusion: We observed a remarkably fast and progressive decline of cardiac morphology and function as well as a progression of rhythm disturbances, even in asymptomatic patients with a potential association between an increase in arrhythmias and progression of myocardial tissue damage, such as focal fibrosis and fat infiltration, exists. These results suggest that MD2 and FSHD1 patients should be carefully followed-up to identify early development of remodeling and potential risks for the development of further cardiac events even in the absence of symptoms. Trial registration ISRCTN, ID ISRCTN16491505. Registered 29 November 2017 – Retrospectively registered, http://www.isrctn.com/ISRCTN16491505 [ABSTRACT FROM AUTHOR]

The treatment of complicated chronic aortic dissection remains controversial. We previously reported encouraging early results with the stent-assisted balloon-induced intimal disruption and relamination of aortic dissection (STABILISE) technique for treating complicated acute aortic dissections. However, to date there have been no specific reports on the treatment of complicated chronic aortic dissections with this technique. The aim of this study was to assess the results of the STABILISE technique to treat complicated chronic aortic dissection. A single-center prospectively maintained database enrolled all patients hospitalized for aortic dissection at our institution. Inclusion criteria for the STABILISE procedure at the chronic stage of dissection (>3 months) were postdissection aneurysm with a diameter >55 mm or rapid aortic diameter growth >5 mm/6 months. We reviewed all patients treated for complicated chronic aortic dissection with the STABILISE technique. Patients were monitored at 3, 6, and 12 months and annually thereafter with clinical, imaging, and laboratory studies. Outcome analyses included survival, rupture, spinal cord ischemia, endoleak, morbidity (cardiac, renal, or pulmonary), reinterventions, false lumen patency, and aneurysm growth. Between September 2015 and December 2018, 17 patients underwent a STABILISE procedure for complicated chronic aortic dissection of the descending aorta. Fifteen patients were treated for remaining chronic distal thoracoabdominal aortic dissection after acute DeBakey type I aortic dissection repair, and 2 patients were treated for chronic type B aortic dissection. The median patient age was 61 years (range, 46-67 years). The median interval between the onset of acute symptoms and the procedure was 9 months (range, 3-67 months). Indications for the STABILISE procedure were a rapidly growing dissected aortic diameter >5 mm/6 months in 13 patients and aneurysmal evolution of the descending thoracic aorta >55 mm in 4 patients. There were no cases of in-hospital death, stroke, spinal cord ischemia, ischemic colitis, or renal failure necessitating dialysis. The median duration of follow-up was 17 months (range, 5-28.5 months). At the last computed tomography scan, 15 patients (88%) had complete false lumen thrombosis of the treated thoracoabdominal aorta down to the renal arteries. None of the patients had aortic growth at treated thoracoabdominal aorta level. One patient developed a proximal type 1 endoleak and required reintervention. Regarding the untreated aortoiliac level below the renal arteries, 11 patients had persistent false lumen patency, and 1 patient developed a common iliac artery aneurysm. All the other patients had stable infrarenal aortoiliac diameters. No late deaths were reported during follow-up. The STABILISE technique is a safe and effective means of performing immediate, complete aortic remodeling of the thoracoabdominal aorta in patients with complicated chronic aortic dissection, stabilizing the diameter of the dissected aorta. [ABSTRACT FROM AUTHOR]

Superior capsule reconstruction (SCR) has been developed to improve shoulder function and relieve pain in the treatment of irreparable rotator cuff tears. Previous studies have reported that graft healing can enhance favorable outcomes after SCR. On the other hand, graft tears often lead to less desirable outcomes and sometimes require additional surgical procedures. However, the healing process underlying this remains unclear. In this study, we aimed to investigate histologic changes occurring during the healing process associated with autologous fascia lata graft after SCR in vivo. We hypothesized that (1) autologous fascia lata graft can regenerate the fibrocartilaginous insertion into both the greater tuberosity and superior glenoid and (2) the midsubstance of the grafted fascia gradually remodels into tendon- and/or ligament-like tissue after SCR. Irreparable supraspinatus tendon defects were created in 24 mature Japanese white rabbits (age, 6 months; mean weight, 3.2 kg). Four weeks after creation of the defects, the right shoulders were subjected to SCR using autologous fascia lata grafts. The left shoulders were left untreated. Samples from the shoulders were harvested at 4, 8, 12, and 16 weeks after surgery to undergo histologic and immunohistochemical examinations. Macroscopically, we did not observe graft tears after SCR in our experiments. Histologically, the number of chondrocyte-like cells gradually increased, and the extracellular matrices around those cells contained glycosaminoglycan at the fascia-bone junction after SCR. The unmineralized fibrocartilage, mineralized fibrocartilage, and tidemark were observed 16 weeks after SCR. The distribution of type II collagen presented a pattern similar to that of a normal tendon and ligament insertion. The cells and collagen fiber gradually oriented parallelly to the long axis in the midsubstance of the grafted fascia lata. Additionally, type III collagen was replaced with type I collagen in the midsubstance of the grafted fascia lata after SCR. SCR using fascia lata autograft regenerated the fibrocartilaginous insertion at both the greater tuberosity and superior glenoid. The midsubstance of the grafted fascia gradually remodeled into tendon- and/or ligament-like tissue. These results suggest that the fascia lata autograft has the capacity for graft-to-bone healing and remodeling after SCR. [ABSTRACT FROM AUTHOR]

The epidemiology, clinical features and outcome of myocardial infarction (MI) display significant differences between men and women. Prominent sex differences have also been suggested in left ventricular (LV) remodeling after MI. Ventricular remodeling refers to a deterioration of LV geometry and function often leading to heart failure (HF) development and an increased risk of adverse cardiovascular events. Women have a lower propensity to the acquisition of a spherical geometry and LV dysfunction. These differences can be attributed at least partially to a lower frequency of transmural infarction and smaller areas of microvascular obstruction in women, as well as to a less prominent activation of neuroendocrine systems and apoptotic, inflammatory and profibrotic pathways in women. Estrogens might play a role in this difference, which could partially persist even after the menopause because of a persisting intramyocardial synthesis of estrogens in women. Conversely, androgens may exert a detrimental influence. Future studies should better clarify sex differences in the predictors, clinical correlates, prognostic impact and disease mechanisms of remodeling, as well as the existence of sex-specific therapeutic targets. This research effort should hopefully allow to optimize the treatment of MI during the acute and post-acute phase, possibly through different therapeutic strategies in men and women, with the goal of reducing the risk of HF development and improving patient outcome. • The ventricular remodeling after MI differs between men and women. • Women have a lower propensity to remodeling. • Estrogens might contribute to this gender difference. • Gender-specific therapeutic targets have not emerged so far. [ABSTRACT FROM AUTHOR]

Background: The cardiac muscle has the ability to adapt to different loading conditions. We analyzed the associations of the age-related decreasing handgrip strength (HGS), a marker of muscular fitness, on cardiac structure and function in a community-based sample.Methods: We performed cross-sectional analyses of 4646 subjects (2554 women; 55.0%) aged 20 to 93 years from two independent cohorts of the Study of Health in Pomerania (SHIP-2 and SHIP-TREND-0). We analyzed the associations of HGS with structural and functional left and right ventricular (LV and RV) and left atrial (LA) parameters as determined by echocardiography and magnetic resonance imaging (MRI) as well with log-transformed NT-proBNP values using multivariable-adjusted linear regression models.Results: MRI data showed that a 1 kg lower HGS was associated with a 0.40 mL (95% confidence interval: 0.26 to 0.54; p < 0.001) lower LV end-diastolic volume, a 0.011 mm (0.005 to 0.018; p = 0.001) lower LV wall-thickness, a 0.59 g (0.43 to 0.75; p < 0.001) lower LV mass, a 0.58 mL/beat (0.43 to 0.74; p < 0.001) lower LV stroke volume, a 0.03 L/min (0.02 to 0.04; p < 0.001) lower LV cardiac output, a 0.48 mL (0.27 to 0.68; p < 0.001) lower LA end-diastolic volume, and a 1.02 mL (0.71 to 1.32) lower RV end-diastolic volume. Similar findings were observed for echocardiographic parameters. Moreover, lower HGS was associated with higher echocardiographic LV diastolic stiffness and NT-proBNP levels.Conclusions: In this large population-based sample, lower muscular fitness as assessed by HGS was associated with lower LV wall thickness and mass as well as with smaller chamber size, stroke volume and cardiac output of the LV, LA and RV. Moreover, HGS was inversely related to LV diastolic stiffness and NT-proBNP values. These outcomes might demonstrate the effects of an aging-related decrease in physical activity and lower muscular fitness on the heart - "the sedentary's heart". [ABSTRACT FROM AUTHOR]

Background: The heart has the capacity to adapt to different demands. The pathophysiological mechanisms involved with sedentarism are not fundamentally the opposite of those related with physical activity and regular exercise. We investigated the impact of lower cardiorespiratory fitness (CRF) on heart's plasticity and function in a population-based setting.Methods: We used data from 1165 participants (539 women; 46.3%) aged 21-81 years from two independent cohorts of the Study of Health in Pomerania (SHIP-2 and SHIP-TREND-0). We analyzed the cross-sectional associations of peak oxygen uptake (VO2peak), determined by symptom-limited cardiopulmonary exercise testing, with structural and functional left ventricular (LV) and left atrial (LA) parameters determined by magnetic resonance imaging (MRI) using multivariable- adjusted linear regression models.Results: A 1 L/min lower VO2peak was associated with a 10.5 g (95% confidence interval: 8.00 to 12.9; p < 0.001) lower LV mass, a 14.8 mL (10.9 to 18.6; p < 0.001) lower LV end-diastolic volume, a 0.29 mm (0.19 to 0.40; p < 0.001) lower LV wall-thickness, a 8.85 mL/beat (6.53 to 11.2; p < 0.001) lower LV stroke volume, a 0.42 L/min (0.25 to 0.60; p < 0.001) lower LV cardiac output and a 7.51 mL (3.88 to 11.1; p < 0.001) lower LA end-diastolic volume. Moreover, there were no associations with a concentric or eccentric remodeling and LV and LA ejection fraction.Conclusions: Lower CRF was associated with a smaller heart, LV wall-thickness and mass, LV and LA stroke volume and cardiac output. Conversely, there was no association with LA and LV ejection fraction. Our cross-sectional observations are consistent with cardiac adaptations reflecting reduced volume loading demands of a sedentary lifestyle - "the sedentary's heart". [ABSTRACT FROM AUTHOR]