Progression of preclinical diastolic dysfunction to the development of symptoms

de, Daniel D. Correa; Hodge, David O.; Slusser, Joshua P.; Redfield, M. M.; Simari, Robert D.; Burnett, John C.; Chen, Horng H.

doi:10.1136/hrt.2009.177980

Cited by 78 publications

(60 citation statements)

References 20 publications

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“…Humans with metabolic derangements such as obesity, hypertension, hyperglycemia, and dyslipidemia-all recognized as important risk factors for CKD and cardiovascular disease 23,24 often present with preclinical diastolic dysfunction, 25 diastolic heart failure, or HFpEF. 26,27 In current and previous reports, we could validate that the ZSF1 Ob animals share these characteristics with patients with metabolic syndrome 2 : ZSF1 Ob rats are obese (65% and 45% increase compared with WKY and ZSF1 Ln, respectively, Furthermore, CRMS in humans is defined by the presence of metabolic syndrome in addition to insulin resistance, microalbuminurina, and reduced renal function.…”

Section: Zsf1 Ob Rats As a Suitable Model For Crmsmetabolic Syndrome mentioning

confidence: 99%

Distinct Endothelial Cell Responses in the Heart and Kidney Microvasculature Characterize the Progression of Heart Failure With Preserved Ejection Fraction in the Obese ZSF1 Rat With Cardiorenal Metabolic Syndrome

Dijk

Oosterhuis

et al. 2016

Circ: Heart Failure

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Background— The combination of cardiac and renal disease driven by metabolic risk factors, referred to as cardiorenal metabolic syndrome (CRMS), is increasingly recognized as a critical pathological entity. The contribution of (micro)vascular injury to CRMS is considered to be substantial. However, mechanistic studies are hampered by lack of in vivo models that mimic the natural onset of the disease. Here, we evaluated the coronary and renal microvasculature during CRMS development in obese diabetic Zucker fatty/Spontaneously hypertensive heart failure F1 hybrid (ZSF1) rats. Methods and Results— Echocardiographic, urine, and blood evaluations were conducted in 3 groups (Wistar-Kyoto, lean ZSF1, and obese ZSF1) at 20 and 25 weeks of age. Immunohistological evaluation of renal and cardiac tissues was conducted at both time points. At 20 and 25 weeks, obese ZSF1 rats showed higher body weight, significant left ventricular hypertrophy, and impaired diastolic function compared with all other groups. Indices of systolic function did not differ between groups. Obese ZSF1 rats developed hyperproliferative vascular foci in the subendocardium, which lacked microvascular organization and were predilection sites of inflammation and fibrosis. In the kidney, obese ZSF1 animals showed regression of the peritubular and glomerular microvasculature, accompanied by tubulointerstitial damage, glomerulosclerosis, and proteinuria. Conclusions— The obese ZSF1 rat strain is a suitable in vivo model for CRMS, sharing characteristics with the human syndrome during the earliest onset of disease. In these rats, CRMS induces microvascular fibrotic responses in heart and kidneys, associated with functional impairment of both organs.

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Section: Zsf1 Ob Rats As a Suitable Model For Crmsmetabolic Syndrome mentioning

confidence: 99%

Distinct Endothelial Cell Responses in the Heart and Kidney Microvasculature Characterize the Progression of Heart Failure With Preserved Ejection Fraction in the Obese ZSF1 Rat With Cardiorenal Metabolic Syndrome

Dijk

Oosterhuis

et al. 2016

Circ: Heart Failure

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“…26 Insufficient antioxidant response could be particularly important for understanding the complex and interactive mechanisms underlying the progression from asymptomatic to symptomatic LVDD. 3,4 Study limitations Although we did not perform exercise echocardiography for evaluating actual diastolic dynamics during exercise, we used CPET, which allowed us to assess the contribution of ventilation to functional capacity.…”

Section: Mechanisms Underlying Reduced Exercise Tolerance In Hypertenmentioning

confidence: 99%

“…[1][2][3][4] Despite the fact that the initial clinical symptoms predominantly occur during exercise, most studies of hypertensive patients have focused on the parameters of LVDD while at rest. 2,[5][6][7] Cardiopulmonary exercise testing (CPET) is a recommended technique for the evaluation of the putative mechanism that underlies exercise intolerance in patients with heart failure.…”

Section: Introductionmentioning

confidence: 99%

Cardiopulmonary exercise testing and its relation to oxidative stress in patients with hypertension

et al. 2012

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An increase in reactive oxygen species has been implicated in the pathologies of hypertension. This study was designed to evaluate antioxidant activity in hypertensive patients and to assess the relationship between oxidative stress and exercise tolerance in hypertensive patients with mild left ventricular diastolic dysfunction (LVDD). A total of 42 patients, aged 51 ± 9 years, with a long history of hypertension and mild LVDD (mitral flow velocities-E/A o1, deceleration time of E 4220 ms, and preserved ejection fraction-EF 450%), and 30 controls without cardiovascular disease, aged 50 ± 7 years, underwent cardiopulmonary exercise testing (CPET). Peak oxygen uptake (peak VO 2 ), oxygen pulse (VO 2 /heart rate (HR)) and ventilatory anaerobic threshold (VAT) were obtained during CPET. Antioxidant activity of superoxide dismutase (SOD) and glutathione peroxidase in the blood was measured before and after exercise. Reduced peak VO 2 (1715 ± 426 vs. 2083±465 ml min À1 , Po0.001), VO 2 /HR (12.0±2.8 vs. 14.6±3.3 ml per beat, Po0.001) and percentage of peak VO 2 at VAT (55.5 ± 15.8% vs. 64.5 ± 14.7%, P ¼ 0.007) were observed in hypertensive patients, compared with controls. Antioxidant protection was significantly attenuated in hypertensive patients, compared with controls, before (945 vs. 1006, P ¼ 0.012) and after exercise (954 vs. 1051, Po0.001). The level of SOD before and after exercise was significantly associated with LVDD in hypertensive patients (P ¼ 0.012 and 0.02, respectively). In addition, the degree of LVDD before exercise (E/A) influenced the degree of exercise capability (peak VO 2 ) (P ¼ 0.016). Asymptomatic hypertensive patients with mild LVDD had reduced cardiopulmonary capacity, accurately identified by CPET. The redox state in hypertensive patients was significantly related to LVDD and exercise tolerance. Attenuated antioxidant protection was associated with long-term hypertension.

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“…The second hypothesis states that the presence of CAD with (silent) myocardial ischemia can cause impairment in myocyte relaxation and hence in diastolic function without obvious impairment of LV ejection fraction. 28,32,33 Furthermore, the myocardial microcirculation in patients with PXE also shows features reminiscent of PXE including mineralization and fragmentation of the elastic fibers, which might also compromise the myocardial oxygen supply. 25 Nevertheless, none of the PXE subjects enrolled in this study had clinical evidence of myocardial ischemia.…”

mentioning

confidence: 99%

Characterization of Cardiovascular Involvement in Pseudoxanthoma Elasticum Families

Campens

Vanakker

Trachet

et al. 2013

ATVB

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Objective-Pseudoxanthoma elasticum (PXE) is an autosomal recessive connective tissue disorder with involvement of the skin, the retina, and the cardiovascular system. Cardiovascular involvement is mainly characterized by mineralization and fragmentation of elastic fibers of blood vessels and premature atherosclerosis. We conducted an ultrasound study to investigate the cardiovascular phenotype and to propose recommendations for the management of patients with PXE and heterozygous ABCC6 mutation carriers. Approach and Results-Thirty-two patients, 23 carriers, and 28 healthy volunteers underwent cardiac and vascular ultrasound studies. Cardiac imaging revealed left ventricular diastolic dysfunction in patients with PXE with a significantly prolonged deceleration time and lower septal early diastolic velocities of the mitral annulus compared with controls. Carriers also demonstrated significantly prolonged deceleration time. Carotid-to-femoral pulse wave velocity was significantly increased in patients with PXE when compared with carriers and controls. Vascular imaging revealed a high prevalence of peripheral artery disease in both patients and carriers and a significantly higher carotid intima-media thickness compared with controls. Conclusions-The results of this study clearly demonstrate impaired left ventricular diastolic function, impairment of the elastic properties of the aorta, and a high prevalence of peripheral artery disease in patients with PXE. Carriers also seem to exhibit a cardiovascular phenotype with mainly mild diastolic dysfunction and accelerated atherosclerosis. Increased awareness for cardiovascular events in both patients and heterozygous carriers is warranted. The ABCC6 gene (chrom. 16p13.1) codes for an ATPdependent transmembrane transporter, which is most abundant in the liver and kidney. Remarkably, the expression of the ABCC6 transporter in tissues clinically affected by PXE is very low. 19 This observation led to the hypothesis that PXE is primarily a metabolic disorder in which circulating serum factor(s) plays a role. 17 Another, and probably complimentary, pathogenetic mechanism is the so-called cellular hypothesis in which fibroblast perturbation may evoke local mineralization and elastic fiber alterations. This hypothesis is based on the observation that elastic fiber alterations are not present homogeneously throughout the skin and blood vessels of patients with PXE, but only in peculiar regions. Moreover, PXE skin fibroblasts exhibit a distinct behavior with altered biosynthetic expression profile and cell-cell and cell-matrix interactions compared with fibroblasts from normal subjects. [20][21][22] This study focuses on the cardiovascular phenotype of patients with PXE and carriers. Cardiovascular changes in patients with PXE are characterized by (1) mineralization and fragmentation of elastic fibers of the internal elastic lamina, medial and adventitial layers of medium-sized arteries and aorta, as well as of the endocardium, pericardium, connective tissue around vessels in t...

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Progression of preclinical diastolic dysfunction to the development of symptoms

Cited by 78 publications

References 20 publications

Distinct Endothelial Cell Responses in the Heart and Kidney Microvasculature Characterize the Progression of Heart Failure With Preserved Ejection Fraction in the Obese ZSF1 Rat With Cardiorenal Metabolic Syndrome

Distinct Endothelial Cell Responses in the Heart and Kidney Microvasculature Characterize the Progression of Heart Failure With Preserved Ejection Fraction in the Obese ZSF1 Rat With Cardiorenal Metabolic Syndrome

Cardiopulmonary exercise testing and its relation to oxidative stress in patients with hypertension

Characterization of Cardiovascular Involvement in Pseudoxanthoma Elasticum Families

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