Surgical Timing of Degenerative Mitral Regurgitation: What to Consider

Dolor-Torres, Maria Consolacion; Ling, Lieng H.

doi:10.4250/jcu.2012.20.4.165

Cited by 4 publications

(3 citation statements)

References 56 publications

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“…Mitral regurgitation (MR) is the most frequently diagnosed heart valve lesion in the USA, which occurs largely due to mitral valve prolapse ( 1 , 2 ). Loss of mitral valve competence causes backflow of blood from the left ventricle (LV) into the left atrium (LA) in each heartbeat, which combined with the constant venous return regulated by the peripheral circulation, increases the total volume of blood filling the heart.…”

Section: Introductionmentioning

confidence: 99%

Ultrastructural Adaptation of the Cardiomyocyte to Chronic Mitral Regurgitation

Corporan

Segura²,

Padala

2021

Front. Cardiovasc. Med.

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Introduction: Mitral regurgitation (MR) imposes volume overload on the left ventricle (LV) and elevates wall stress, triggering its adverse remodeling. Pronounced LV dilation, minimal wall thinning, and a gradual decline in cardiac ejection fraction (EF) are observed. The structural changes in the myocardium that define these gross, organ level remodeling are not known. Cardiomyocyte elongation and slippage have both been hypothesized, but neither are confirmed, nor are the changes to the cardiomyocyte structure known. Using a rodent model of MR, we used immunohistochemistry and transmission electron microscopy (TEM) to describe the ultrastructural remodeling of the cardiomyocyte.Methods: Twenty-four male Sprague-Dawley rats (350–400 g) were assigned to two groups: group (1) rats induced with severe MR (n = 18) and group (2) control rats that were healthy and age and weight matched (n = 6). MR was induced in the beating heart using a 23-G ultrasound-guided, transapical needle to perforate the anterior mitral leaflet, and the rats were followed to 2, 10, and 20 weeks (n = 6/time-point). Echocardiography was performed to quantify MR severity and to measure LV volume and function at each time-point. Explanted myocardial tissue were examined with TEM and immunohistochemistry to investigate the ultrastructural changes.Results: MR induced rapid and significant increase in end-diastolic volume (EDV), with a 50% increase by 2 weeks, compared with control. Rise in end-systolic volume (ESV) was more gradual; however, by 20 weeks, both EDV and ESV in MR rats were increased by 126% compared with control. A significant decline in EF was measured at 10 weeks of MR. At the ultrastructural level, as early as 2 weeks after MR, cardiomyocyte elongation and increase in cross-sectional area were observed. TEM depicted sarcomere shortening, with loss of Z-line and I-band. Desmin, a cytoskeletal protein that is uniformly distributed along the length of the cardiomyocyte, was disorganized and localized to the intercalated disc, in the rats induced with MR and not in the controls. In the rats with MR, the linear registry of the mitochondrial arrangement along the sarcomeres was lost, with mitochondrial fragmentation, aggregation around the nucleus, and irregularities in the cristae.Discussion: In the setting of chronic mitral regurgitation, LV dilatation occured by cardiomyocyte elongation, which manifests at the subcellular level as distinct ultrastructural alterations of the sarcomere, cytoskeleton, and mitochondria. Since the cytoskeleton not only provides tensegrity but has functional consequences on myocyte function, further investigation into the impact of cytoskeletal remodeling on progressive heart failure or recovery of function upon correcting the valve lesion are needed.

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Section: Introductionmentioning

confidence: 99%

Ultrastructural Adaptation of the Cardiomyocyte to Chronic Mitral Regurgitation

Corporan

Segura²,

Padala

2021

Front. Cardiovasc. Med.

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“…Symptomatology is an ACC/AHA class I indication for intervention in these patients; however the challenge arises in assessing the presence of symptoms due to the subjective nature of this identification. In addition to determining optimal time of surgical intervention, biomarkers such as NT-pro-BNP are important in risk stratification of patients [ 31 ]. Traditionally, transthoracic echocardiography at both rest and stress has been used in risk stratification of patients prior to intervention; however integration of biomarkers with imaging data continues to be investigated [ 32 ].…”

Section: Role Of Natriuretic Peptides In Assessment Of Patients Wimentioning

confidence: 99%

Clinical Applications of Natriuretic Peptides in Assessment of Valvular Heart Disease

et al. 2015

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Biomarkers such as natriuretic peptides (NPs) have evolving clinical utility beyond the scope of heart failure. The role of NPs in the management of valvular heart disease is a growing area of investigation. NPs have much potential in the assessment of asymptomatic patients with hemodynamically significant valvular lesions who have traditionally been excluded from consideration of surgical intervention. NPs also have a role in the risk stratification of these patients as well as in routine surveillance and monitoring. Together with echocardiographic data and functional status, NPs are being incorporated into the management of valvular heart disease. In this review we examine the evidence for the role of natriuretic peptides in assessment of VHD.

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“…MR is characterized by a systolic reversal of blood from the high-pressure left ventricle (LV) into the low-pressure left atrium through the MV, which increases the diastolic return to the LV in each beat and imposes volume overload on the LV chamber. This volume overload induces rapid LV dilatation and thinning and ultimately leads to congestive heart failure and death (2,4). Timely intervention to repair the MR can halt progressive volume overload-induced heart failure, but the temporal changes in the LV after the onset of MR are not well described to trigger such interventions.…”

Section: Introductionmentioning

confidence: 99%

Temporal changes in myocardial collagen, matrix metalloproteinases, and their tissue inhibitors in the left ventricular myocardium in experimental chronic mitral regurgitation in rodents

Corporan

Onohara

Hernandez-Merlo

et al. 2018

American Journal of Physiology-Heart and Circulatory Physiology

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Mitral regurgitation(MR) imposes left ventricular (LV)volume overload, triggering rapid ventricular dilatation, increased myocardial compliance and ultimately cardiac dysfunction. Breakdown of extracellular matrix(ECM) is hypothesized to drive these rapid changes, partially from an imbalance in the matrix metalloproteinases(MMPs) and their tissue inhibitors(TIMPs). In this study, we developed a rat model of severe MR that mimics the human condition, and investigated the temporal changes in ECM related genes, collagen biosynthesis proteins, and proteolytic enzymes, over 20 weeks. Male Sprague-Dawley rats were anesthetized to a surgical plane with mechanical ventilation, and a thoracotomy was performed to expose the apex. Using transesophageal ultrasound guidance, a needle was inserted into the beating heart to perforate the anterior mitral leaflet and create severe MR. Animals were survived for 20 weeks, with some animals terminated at 2,10 and 20 weeks for analysis of LV tissue. A sham group that underwent the same surgery without mitral leaflet perforation and MR were used as controls. At 2 weeks post-MR, increased collagen gene expression was measured, but protein levels of collagen did not corroborate this finding. In parallel, MMP1-TIMP4, MMP2-TIMP1, MMP2-TIMP3 ratios were significantly elevated indicating a proteolytic milieu in the myocardium, possibly causing collagen degradation. By 20 weeks, may of the initial differences seen in the proteolytic ratios were not observed, with an increase in collagen compared to the 2-week timepoint. Altogether this data indicates that imbalance in MMP-TIMP ratio may occur early and potentially contribute to the early dilatation and compliance observed structurally.

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Surgical Timing of Degenerative Mitral Regurgitation: What to Consider

Cited by 4 publications

References 56 publications

Ultrastructural Adaptation of the Cardiomyocyte to Chronic Mitral Regurgitation

Ultrastructural Adaptation of the Cardiomyocyte to Chronic Mitral Regurgitation

Clinical Applications of Natriuretic Peptides in Assessment of Valvular Heart Disease

Temporal changes in myocardial collagen, matrix metalloproteinases, and their tissue inhibitors in the left ventricular myocardium in experimental chronic mitral regurgitation in rodents

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