Analysis of age-related left ventricular collagen remodeling in living donors: Implications in arrhythmogenesis

García-Mendívil, Laura; Pérez-Zabalza, María; Mountris, Konstantinos A.; Duwé, Sam; Smisdom, Nick; Pérez, Marta; Luján, Lluís; Wolfs, Esther; Driesen, Ronald B.; Vallejo-Gil, José María; Fresneda-Roldán, Pedro Carlos; Fañanás-Mastral, Javier; Vázquez-Sancho, Manuel; Matamala-Adell, Marta; Sorribas-Berjón, Juan Fernando; Bellido-Morales, Javier André; Mancebón-Sierra, Francisco Javier; Vaca-Núñez, Alexánder Sebastián; Ballester-Cuenca, Carlos; Oliván-Viguera, Aida; Diez, Emiliano; Ordovás, Laura; Pueyo, Esther

doi:10.1016/j.isci.2022.103822

Cited by 5 publications

(7 citation statements)

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“…Fibrosis is also a well-known arrhythmogenic substrate as it can hamper proper impulse propagation [ 4 ]. Recently, similar observations have been reported in humans and large animals (pig) in relation to age and fibrosis (amount and spatial distribution), and specifically related to collagen as chief component of the ventricular extracellular matrix [ 5 , 6 ].…”

Section: Introductionsupporting

confidence: 57%

“…Age-related morphological alterations in the marmoset heart were investigated through TPEF and SHG imaging [ 43 ]. More recently, Garcia-Mendivil and colleagues performed quantitative and spatial characterization of collagen in the left ventricle (LV) myocardium of young to old pigs, and human donors [ 6 ] to analyze its potential implications for ventricular arrhythmia development with age. Consistency between pig and human results led the authors to consider the pig as a relevant model of age-related heart changes.…”

Section: Introductionmentioning

confidence: 99%

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Analysis of age-related changes in the left ventricular myocardium with multiphoton microscopy

Bueno,

Martínez-Ojeda,

Pérez-Zabalza

et al. 2024

Biomed. Opt. Express

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Aging induces cardiac remodeling, resulting in an increase in the risk of suffering heart diseases, including heart failure. Collagen deposition increases with age and, together with sarcomeric changes in cardiomyocytes, may lead to ventricular stiffness. Multiphoton (MP) microscopy is a useful technique to visualize and detect variations in cardiac structures in a label free fashion. Here, we propose a method based on MP imaging (both two-photon excitation fluorescence (TPEF) and second harmonic generation (SHG) modalities) to explore and objectively quantify age-related structural differences in various components of cardiac tissues. Results in transmural porcine left ventricle (LV) sections reveal significant differences when comparing samples from young and old animals. Collagen and myosin SHG signals in old specimens are respectively 3.8x and >6-fold larger than in young ones. Differences in TPEF signals from cardiomyocyte were ∼3x. Moreover, the increased amount of collagen in old specimens results in a more organized pattern when compared to young LV tissues. Since changes in collagen and myosin are associated with cardiac dysfunction, the technique used herein might be a useful tool to accurately predict and measure changes associated with age-related myocardium fibrosis, tissue remodeling and sarcomeric alterations, with potential implications in preventing heart disease.

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Section: Introductionsupporting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

Analysis of age-related changes in the left ventricular myocardium with multiphoton microscopy

Bueno,

Martínez-Ojeda,

Pérez-Zabalza

et al. 2024

Biomed. Opt. Express

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“…Adapted from García-Mendívil et al. 1 Using the myocardial tissue mask (3) and the collagen mask (5), the percentage of collagen (

) is calculated as the number of activated pixels in the collagen mask (

) divided by the sum of activated pixels in the myocardial tissue (

) and the collagen masks:

where: >Nc = nnz(collagen_mask); (6) >Nm = nnz(myocardial_tissue_mask); The MATLAB function “nnz” returns the number of nonzero elements in a specific matrix. Note: The obtained binary masks are used in subsequent analyses.…”

Section: Step-by-step Methods Detailsmentioning

confidence: 99%

“…Extracted from García-Mendívil et al. 1 Compute the percentage of lipofuscin (

) as the number of activated pixels in the lipofuscin mask (

) divided by the activated pixels in the myocardial tissue mask (

where: >N l = nnz(binary_lipofuscin_mask); (8) >N m = nnz(myocardial_tissue_mask); Note: The MATLAB functions “imbinarize” and “nnz” are described in step 11. …”

Section: Step-by-step Methods Detailsmentioning

confidence: 99%

Automatic quantification of myocardial remodeling features in human ventricular tissue from label-free microscopy

García-Mendívil,

Pérez-Zabalza,

Duwé

et al. 2023

STAR Protocols

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“…However, this benefit was primarily restricted to heart failure with reduced ejection fraction (HFrEF) and not HFpEF [8]. This difference may have been secondary to the heterogeneity of the HFpEF clinical syndrome as reflected by the pathophysiological role of comorbidities, e.g., hyperinsulinemia in non-insulin-dependent diabetes mellitus as the cause of cardiac remodeling [9], elevated afterload leading to left ventricular (LV) hypertrophy in hypertension [10], the presence of epicardial adipose tissue resulting in restricted relaxation of the left chambers [11], and age-related fibrotic changes in older patients [12].…”

Section: Introductionmentioning

confidence: 99%

Potential Benefits of Sodium-Glucose Transporter-2 Inhibitors in the Symptomatic and Functional Status of Patients With Heart Failure: A Systematic Review and Meta-Analysis

Bhalla¹,

AlQabandi²,

Nandula³

et al. 2022

Cureus

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This review evaluates the potential benefits of sodium-glucose transporter-2 (SGLT-2) inhibitors on symptom burden/health-related quality of life (HRQoL), functional improvement, hospitalization for heart failure (HHF), cardiovascular mortality (CVM), and all-cause mortality (ACM) in patients with heart failure (HF) with reduced or preserved ejection fraction (EF). We analyzed 12 randomized clinical trials (RCTs) accessed through 11 records and three secondary analyses from PubMed and Scopus following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020 guidelines. These studies evaluated 23,389 patients treated with either an SGLT-2 inhibitor or placebo in addition to the standard of care. Four studies recruited diabetic patients, some of whom had HF at the baseline and were evaluated as a subgroup. One study had diabetes and HF present in all patients at the baseline. Ten studies recruited patients with HF at their baseline irrespective of diabetic status. Eight studies evaluated the SGLT-2 inhibitors for a composite of hospitalization for heart failure or cardiovascular mortality (HHF/CVM) and ACM. Five of these studies showed a decreased risk for HHF/CVM, and two showed a reduced risk for ACM. One trial showed benefits in patients with heart failure with reduced ejection fraction (HFrEF) only and not in heart failure with preserved ejection fraction (HFpEF). Other studies revealed benefits but did not reach statistical significance. Ten studies assessed the SGLT-2 inhibitors for improvement in symptoms and HRQoL; four demonstrated a significant improvement, three showed a slight improvement, and three did not find any benefit. Five trials evaluated participants' functional progress by assessing for a six-minute walk test (6MWT). Two studies showed a significant increase in the distance walked by the patient, while three others did not. The SGLT-2 inhibitors reduce the risk of HHF/CVM irrespective of ejection fraction and result in a symptomatic improvement.

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Analysis of age-related left ventricular collagen remodeling in living donors: Implications in arrhythmogenesis

Cited by 5 publications

References 50 publications

Analysis of age-related changes in the left ventricular myocardium with multiphoton microscopy

Analysis of age-related changes in the left ventricular myocardium with multiphoton microscopy

Automatic quantification of myocardial remodeling features in human ventricular tissue from label-free microscopy

Potential Benefits of Sodium-Glucose Transporter-2 Inhibitors in the Symptomatic and Functional Status of Patients With Heart Failure: A Systematic Review and Meta-Analysis

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