Fibrosis and expression of extracellular matrix proteins in human interventricular septum in aortic valve stenosis and regurgitation.

Valvular heart disease leads to ventricular pressure and/or volume overload. Pressure overload leads to fibrosis, which might regress with its resolution, but the limits and details of this reverse remodeling are not known. To gain more insight into the extent and nature of cardiac fibrosis in valve disease, we analyzed needle biopsies taken from the interventricular septum of patients undergoing surgery for valve replacement focusing on the expression and distribution of major extracellular matrix protein involved in this process. Proteomic analysis performed using mass spectrometry revealed an excellent correlation between the expression of collagen type I and III, but there was little correlation with the immunohistochemical staining performed on sister sections, which included antibodies against collagen I, III, fibronectin, sarcomeric actin, and histochemistry for wheat germ agglutinin. Surprisingly, the immunofluorescence intensity did not correlate significantly with the gold standard for fibrosis quantification, which was performed using Picrosirius Red (PSR) staining, unless multiplexed on the same tissue section. There was also little correlation between the immunohistochemical markers and pressure gradient severity. It appears that at least in humans, the immunohistochemical pattern of fibrosis is not clearly correlated with standard Picrosirius Red staining on sister sections or quantitative proteomic data, possibly due to tissue heterogeneity at microscale, comorbidities, or other patient-specific factors. For precise correlation of different types of staining, multiplexing on the same section is the best approach.

Gap Junctional Communication via Connexin43 between Purkinje Fibers and Working Myocytes Explains the Epicardial Activation Pattern in the Postnatal Mouse Left Ventricle.

The mammalian ventricular myocardium forms a functional syncytium due to flow of electrical current mediated in part by gap junctions localized within intercalated disks. The connexin (Cx) subunit of gap junctions have direct and indirect roles in conduction of electrical impulse from the cardiac pacemaker via the cardiac conduction system (CCS) to working myocytes. Cx43 is the dominant isoform in these channels. We have studied the distribution of Cx43 junctions between the CCS and working myocytes in a transgenic mouse model, which had the His-Purkinje portion of the CCS labeled with green fluorescence protein. The highest number of such connections was found in a region about one-third of ventricular length above the apex, and it correlated with the peak proportion of Purkinje fibers (PFs) to the ventricular myocardium. At this location, on the septal surface of the left ventricle, the insulated left bundle branch split into the uninsulated network of PFs that continued to the free wall anteriorly and posteriorly. The second peak of PF abundance was present in the ventricular apex. Epicardial activation maps correspondingly placed the site of the first activation in the apical region, while some hearts presented more highly located breakthrough sites. Taken together, these results increase our understanding of the physiological pattern of ventricular activation and its morphological underpinning through detailed CCS anatomy and distribution of its gap junctional coupling to the working myocardium.

A Narrative Review of the Utilisation of the SHARE Frailty Instruments (SHARE-FI and SHARE-FI75+) in the Literature.

This narrative literature review aimed to examine the utilisation of the Survey of Health, Ageing and Retirement in Europe (SHARE) frailty instruments: SHARE-FI and SHARE-FI75+. We used the Google Scholar "cited by" function (accessed on February 20th, 2023) to identify all citations of the original SHARE-FI and SHARE-FI75+ studies. Included articles were categorised into four themes: epidemiological studies (prevalence and associated factors); associations with geriatric syndromes, diseases and health outcomes; randomised clinical trials (RCTs); and expert consensus and practice guidelines. Of 529 articles screened (446 citing SHARE-FI and 83 citing SHARE-FI75+), 64 (12.1%) were included. Sixteen (25.0%) were epidemiological; 35 (54.7%) described associations; 10 (15.6%) were RCTs; and 3 (4.7%) were expert consensus or practice guidelines. Frailty was associated with older age; female sex; higher morbidity; lower education; social isolation; worse nutrition and mobility; rheumatological, cardiovascular, and endocrine diseases; and greater healthcare utilisation and mortality. SHARE-FI was used in RCTs as entry criterion, controlling variable, and intervention outcome. SHARE-FI and SHARE-FI75+ have been recommended to aid the management of atrial fibrillation anticoagulation and hypertension, respectively. SHARE-FI and SHARE-FI75+, two open access phenotypical frailty measurement tools, have been utilised for a range of purposes, and mostly in epidemiological/associational studies.