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Circulation. Heart Failure Nov 2012Patients with heart failure and preserved ejection fraction (HFpEF) display increased adiposity and multiple comorbidities, factors that in themselves may influence...
BACKGROUND
Patients with heart failure and preserved ejection fraction (HFpEF) display increased adiposity and multiple comorbidities, factors that in themselves may influence cardiovascular structure and function. This has sparked debate as to whether HFpEF represents a distinct disease or an amalgamation of comorbidities. We hypothesized that fundamental cardiovascular structural and functional alterations are characteristic of HFpEF, even after accounting for body size and comorbidities.
METHODS AND RESULTS
Comorbidity-adjusted cardiovascular structural and functional parameters scaled to independently generated and age-appropriate allometric powers were compared in community-based cohorts of HFpEF patients (n=386) and age/sex-matched healthy n=193 and hypertensive, n=386 controls. Within HFpEF patients, body size and concomitant comorbidity-adjusted cardiovascular structural and functional parameters and survival were compared in those with and without individual comorbidities. Among HFpEF patients, comorbidities (obesity, anemia, diabetes mellitus, and renal dysfunction) were each associated with unique clinical, structural, functional, and prognostic profiles. However, after accounting for age, sex, body size, and comorbidities, greater concentric hypertrophy, atrial enlargement and systolic, diastolic, and vascular dysfunction were consistently observed in HFpEF compared with age/sex-matched normotensive and hypertensive.
CONCLUSIONS
Comorbidities influence ventricular-vascular properties and outcomes in HFpEF, yet fundamental disease-specific changes in cardiovascular structure and function underlie this disorder. These data support the search for mechanistically targeted therapies in this disease.
Topics: Aged; Aged, 80 and over; Anemia; Case-Control Studies; Cohort Studies; Comorbidity; Diabetes Mellitus; Echocardiography, Doppler; Female; Heart Atria; Heart Failure; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Kidney Diseases; Male; Obesity; Stroke Volume
PubMed: 23076838
DOI: 10.1161/CIRCHEARTFAILURE.112.968594 -
Journal of Nuclear Medicine : Official... Nov 2013Myocardial metabolic and perfusion imaging is a vital tool for understanding the physiologic consequences of heart failure. We used PET imaging to examine the...
Longitudinal evaluation of left ventricular substrate metabolism, perfusion, and dysfunction in the spontaneously hypertensive rat model of hypertrophy using small-animal PET/CT imaging.
UNLABELLED
Myocardial metabolic and perfusion imaging is a vital tool for understanding the physiologic consequences of heart failure. We used PET imaging to examine the longitudinal kinetics of (18)F-FDG and 14(R,S)-(18)F-fluoro-6-thia-heptadecanoic acid ((18)F-FTHA) as analogs of glucose and fatty acid (FA) to quantify metabolic substrate shifts with the spontaneously hypertensive rat (SHR) as a model of left ventricular hypertrophy (LVH) and failure. Myocardial perfusion and left ventricular function were also investigated using a newly developed radiotracer (18)F-fluorodihydrorotenol ((18)F-FDHROL).
METHODS
Longitudinal dynamic electrocardiogram-gated small-animal PET/CT studies were performed with 8 SHR and 8 normotensive Wistar-Kyoto (WKY) rats over their life cycle. We determined the myocardial influx rate constant for (18)F-FDG and (18)F-FTHA (Ki(FDG) and Ki(FTHA), respectively) and the wash-in rate constant for (18)F-FDHROL (K1(FDHROL)). (18)F-FDHROL data were also used to quantify left ventricular ejection fraction (LVEF) and end-diastolic volume (EDV). Blood samples were drawn to independently measure plasma concentrations of glucose, insulin, and free fatty acids (FFAs).
RESULTS
Ki(FDG) and Ki(FTHA) were higher in SHRs than WKY rats (P < 3 × 10(-8) and 0.005, respectively) independent of age. A decrease in Ki(FDG) with age was evident when models were combined (P = 0.034). The SHR exhibited higher K1(FDHROL) (P < 5 × 10(-6)) than the control, with no age-dependent trends in either model (P = 0.058). Glucose plasma concentrations were lower in SHRs than controls (P < 6 × 10(-12)), with an age-dependent rise for WKY rats (P < 2 × 10(-5)). Insulin plasma concentrations were higher in SHRs than controls (P < 3 × 10(-3)), with an age-dependent decrease when models were combined (P = 0.046). FFA levels were similar between models (P = 0.374), but an increase with age was evident only in SHR (P < 7 × 10(-6)).
CONCLUSION
The SHR exhibited alterations in myocardial substrate use at 8 mo characterized by increased glucose and FA utilizations. At 20 mo, the SHR had LVH characterized by decreased LVEF and increased EDV, while simultaneously sustaining higher glucose and similar FA utilizations (compared with WKY rats), which indicates maladaptation of energy substrates in the failing heart. Elevated K1(FDHROL) in the SHR may reflect elevated oxygen consumption and decreased capillary density in the hypertrophied heart. From our findings, metabolic changes appear to precede mechanical changes of LVH progression in the SHR model.
Topics: Animals; Disease Models, Animal; Fatty Acids; Fatty Acids, Nonesterified; Fluorodeoxyglucose F18; Heart Ventricles; Hypertrophy, Left Ventricular; Insulin; Longitudinal Studies; Male; Multimodal Imaging; Myocardial Perfusion Imaging; Phenotype; Positron-Emission Tomography; Rats; Rats, Inbred SHR; Tomography, X-Ray Computed
PubMed: 24092939
DOI: 10.2967/jnumed.113.120105 -
Scientific Reports Jun 2018The aim of this study was to examine the associations of isolated minor nonspecific ST-T abnormalities (NSSTTA) on 12-lead electrocardiogram (ECG) with left ventricular...
The aim of this study was to examine the associations of isolated minor nonspecific ST-T abnormalities (NSSTTA) on 12-lead electrocardiogram (ECG) with left ventricular (LV) diastolic function and LV geometry on echocardiography. A cross-sectional study comprised of 74,976 Koreans who underwent ECG and echocardiography as part of a comprehensive health examination between March 2011 and December 2014. ECG was coded using Minnesota Code criteria. The frequencies of NSSTTA, impaired LV relaxation, and echocardiographic LVH were 1,139 (1.5%), 21,118 (28.2%), and 1,687 (2.3%) patients, respectively. The presence of NSSTTA was positively associated with the prevalence of impaired LV relaxation and LVH on echocardiography. In a multivariable-adjusted model, the odds ratio (95% CIs) comparing patients with NSSTTA to control patients was 1.55 (1.33-1.80) for impaired LV relaxation and 3.15 (2.51-3.96) for echocardiographic LVH. The association between NSSTTA and impaired LV relaxation was stronger in the intermediate to high cardiovascular disease-risk group than in the low-risk group according to Framingham Risk Score stratification (P for interaction = 0.02). NSSTTA were associated with increased prevalence of impaired LV relaxation and LVH, suggesting NSSTTA as an early indicator of subclinical cardiac dysfunction and geometric abnormalities.
Topics: Adult; Cross-Sectional Studies; Diastole; Echocardiography, Doppler; Electrocardiography; Female; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Odds Ratio; Ventricular Dysfunction, Left; Ventricular Function, Left
PubMed: 29884788
DOI: 10.1038/s41598-018-27028-6 -
Oxidative Medicine and Cellular... 2015Cardiac hypertrophy is the most documented cardiomyopathy following hyperthyroidism in experimental animals. Thyroid hormone-induced cardiac hypertrophy is described as... (Review)
Review
Cardiac hypertrophy is the most documented cardiomyopathy following hyperthyroidism in experimental animals. Thyroid hormone-induced cardiac hypertrophy is described as a relative ventricular hypertrophy that encompasses the whole heart and is linked with contractile abnormalities in both right and left ventricles. The increase in oxidative stress that takes place in experimental hyperthyroidism proposes that reactive oxygen species are key players in the cardiomyopathy frequently reported in this endocrine disorder. The goal of this review is to shed light on the effects of thyroid hormones on the development of oxidative stress in the heart along with the subsequent cellular and molecular changes. In particular, we will review the role of thyroid hormone-induced oxidative stress in the development of cardiomyocyte hypertrophy and associated cardiac dysfunction, as well as the potential effectiveness of antioxidant treatments in attenuating these hyperthyroidism-induced abnormalities in experimental animal models.
Topics: Animals; Antioxidants; Cardiomegaly; Heart Ventricles; Hyperthyroidism; Myocardium; Oxidative Stress; Reactive Oxygen Species; Thyroid Hormones
PubMed: 26146529
DOI: 10.1155/2015/854265 -
European Heart Journal. Cardiovascular... Jan 2012Despite the American Society of Echocardiography (ASE)/European Association of Echocardiography (EAE) recommended the use of left ventricular (LV) mass to diagnose left...
Left ventricular hypertrophy reclassification and death: application of the Recommendation of the American Society of Echocardiography/European Association of Echocardiography.
AIMS
Despite the American Society of Echocardiography (ASE)/European Association of Echocardiography (EAE) recommended the use of left ventricular (LV) mass to diagnose left ventricular hypertrophy (LVH), several laboratories continue to use only the septal thickness by M-mode because it appears easier to measure. Aim of the study was to investigate the discrepancy between the categorization of LVH severity based on measurement of septal thickness and indexed LV mass and the relative prognostic utility of these two methods.
METHODS AND RESULTS
Observational cohort study. Unselected adults (>18 years) referred to the echocardiography laboratory for any indication had septal thickness and LV mass measured by the ASE/EAE formula using LV linear dimensions indexed to body surface area. LVH was categorized as absent, mild, moderate, and severe according to the ASE/EAE guideline sex-specific categorization cut-offs for septal thickness and LV mass. Follow-up for death was obtained from the national death index. A total of 2545 subjects (mean age 61.9 ± 15.8, 53% women, mean diastolic septal thickness 10.3 ± 2.2 mm, and mean indexed LV mass 107.5 ± 37.3 g/m(2)) were enrolled. Agreement between the two methods in classifying LVH degree across the four categories was 52.6% (Kappa = 0.29, 95% confidence interval (CI): 0.26-0.32, P < 0.001). Of the 2513 subjects without severely thickened septum, 472 (18.9%) had severely abnormal indexed LV mass. Vice versa, of the 2045 individuals without severely abnormal indexed LV mass, only 4 (0.1%) were classified as severe LVH by septal thickness. After a mean follow-up of 2.5 ± 1.2 years 121 (4.7%) deaths occurred. Using indexed LV mass partition values there was a graded association between LVH degree and survival. Compared with patients with normal indexed LV mass, the adjusted hazard ratio (HR) for death from all causes was 2.17 for mild (95% CI: 1.23-3.81, P = 0.007), 3.04 for moderate (95% CI: 1.76-5.24, P < 0.001), and 3.81 for severe (95% CI: 2.43-5.97, P < 0.001) LVH by indexed LV mass. The area under the receiver-operator characteristic (ROC) curve for the four degrees of LVH by indexed LV mass was superior [area under the curve (AUC) = 0.66] to that of the septal thickness partition values (AUC = 0.58, P = 0.0004).
CONCLUSION
In a large cohort study of unselected adult outpatients referred to the echocardiography laboratory, the measurements of indexed LV mass applying the ASE/EAE recommended cut-offs yielded remarkable discrepancy in the diagnosis of LVH severity and offered prognostic information beyond that provided by septal thickness only criteria.
Topics: Area Under Curve; Confidence Intervals; Echocardiography; Female; Heart Septum; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Italy; Male; Middle Aged; Practice Guidelines as Topic; Prognosis; Retrospective Studies; Severity of Illness Index; Societies, Medical; Statistics as Topic
PubMed: 21979990
DOI: 10.1093/ejechocard/jer176 -
BMJ Case Reports Apr 2019Left ventricular puncture during a thoracentesis is a rare and unusual complication that has yet to be reported. We report a case in which a 74-year-old woman with...
Left ventricular puncture during a thoracentesis is a rare and unusual complication that has yet to be reported. We report a case in which a 74-year-old woman with dilated ischaemic heart disease suffered from puncture of the left ventricle during a routine ultrasound-guided thoracentesis despite following the recommended protocol and procedures. She became haemodynamically unstable and underwent an emergent thoracotomy for removal of the catheter and repair of the left ventricular wall.
Topics: Aged; Cardiac Catheterization; Drainage; Female; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Postoperative Complications; Punctures; Thoracentesis; Ultrasonography, Interventional
PubMed: 30967447
DOI: 10.1136/bcr-2018-227613 -
American Journal of Physiology. Heart... Mar 2013Right ventricular (RV) and left ventricular (LV) myocardium differ in their pathophysiological response to pressure-overload hypertrophy. In this report we use... (Comparative Study)
Comparative Study
Right ventricular (RV) and left ventricular (LV) myocardium differ in their pathophysiological response to pressure-overload hypertrophy. In this report we use microarray and proteomic analyses to identify pathways modulated by LV-aortic banding (AOB) and RV-pulmonary artery banding (PAB) in the immature heart. Newborn New Zealand White rabbits underwent banding of the descending thoracic aorta [LV-AOB; n = 6]. RV-PAB was achieved by banding the pulmonary artery (n = 6). Controls (n = 6 each) were sham-manipulated. After 4 (LV-AOB) and 6 (RV-PAB) wk recovery, the hearts were removed and matched RNA and proteins samples were isolated for microarray and proteomic analysis. Microarray and proteomic data demonstrate that in LV-AOB there is increased transcript expression levels for oxidative phosphorylation, mitochondria energy pathways, actin, ILK, hypoxia, calcium, and protein kinase-A signaling and increased protein expression levels of proteins for cellular macromolecular complex assembly and oxidative phosphorylation. In RV-PAB there is also an increased transcript expression levels for cardiac oxidative phosphorylation but increased protein expression levels for structural constituents of muscle, cardiac muscle tissue development, and calcium handling. These results identify divergent transcript and protein expression profiles in LV-AOB and RV-PAB and provide new insight into the biological basis of ventricular specific hypertrophy. The identification of these pathways should allow for the development of specific therapeutic interventions for targeted treatment and amelioration of LV-AOB and RV-PAB to ameliorate morbidity and mortality.
Topics: Animals; Animals, Newborn; Aorta, Thoracic; Disease Models, Animal; Heart Ventricles; Hypertrophy, Left Ventricular; Hypertrophy, Right Ventricular; Ligation; Myocardium; Oligonucleotide Array Sequence Analysis; Proteomics; Rabbits; Transcriptome; Ventricular Pressure
PubMed: 23262132
DOI: 10.1152/ajpheart.00802.2012 -
American Journal of Physiology. Heart... Jun 2018We have previously shown that protein tyrosine phosphatase 1B (PTP1B) inactivation in mice [PTP1B-deficient (PTP1B) mice] improves left ventricular (LV) angiogenesis,...
We have previously shown that protein tyrosine phosphatase 1B (PTP1B) inactivation in mice [PTP1B-deficient (PTP1B) mice] improves left ventricular (LV) angiogenesis, perfusion, remodeling, and function and limits endothelial dysfunction after myocardial infarction. However, whether PTP1B inactivation slows aging-associated cardiovascular dysfunction remains unknown. Wild-type (WT) and PTP1B mice were allowed to age until 18 mo. Compared with old WT mice, in which aging increased the LV mRNA expression of PTP1B, old PTP1B mice had 1) reduced cardiac hypertrophy with decreased LV mRNA levels of hypertrophic markers and atrial and brain natriuretic peptides, 2) lower LV fibrosis (collagen: 16 ± 3% in WT mice and 5 ± 3% in PTP1B mice, P < 0.001) with decreased mRNA levels of transforming growth-factor-β and matrix metalloproteinase-2, and 3) higher LV capillary density and lower LV mRNA level of hypoxic inducible factor-1α, which was associated over time with a higher rate of proangiogenic M2 type macrophages and a stable LV mRNA level of VEGF receptor-2. Echocardiography revealed an age-dependent LV increase in end-diastolic volume in WT mice together with alterations of fractional shortening and diastole (transmitral Doppler E-to-A wave ratio). Invasive hemodynamics showed better LV systolic contractility and better diastolic compliance in old PTP1B mice (LV end-systolic pressure-volume relation: 13.9 ± 0.9 in WT mice and 18.4 ± 1.6 in PTP1B mice; LV end-diastolic pressure-volume relation: 5.1 ± 0.8 mmHg/relative volume unit in WT mice and 1.2 ± 0.3 mmHg/relative volume unit in PTP1B mice, P < 0.05). In addition, old PTP1B mice displayed a reduced amount of LV reactive oxygen species. Finally, in isolated resistance mesenteric arteries, PTP1B inactivation reduced aging-associated endothelial dysfunction (flow-mediated dilatation: -0.4 ± 2.1% in WT mice and 8.2 ± 2.8% in PTP1B mice, P < 0.05). We conclude that PTP1B inactivation slows aging-associated LV remodeling and dysfunction and reduces endothelial dysfunction in mesenteric arteries. NEW & NOTEWORTHY The present study shows that protein tyrosine phosphatase 1B inactivation in aged mice improves left ventricular systolic and diastolic function associated with reduced adverse cardiac remodeling (hypertrophy, fibrosis, and capillary rarefaction) and limits vascular endothelial dysfunction. This suggests that protein tyrosine phosphatase 1B inhibition could be an interesting treatment approach in age-related cardiovascular dysfunction.
Topics: Age Factors; Aging; Animals; Disease Models, Animal; Fibrosis; Gene Expression Regulation, Enzymologic; Heart Failure; Heart Ventricles; Hemodynamics; Hypertrophy, Left Ventricular; Male; Mesenteric Arteries; Mice, Inbred BALB C; Mice, Knockout; Neovascularization, Physiologic; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling
PubMed: 29569957
DOI: 10.1152/ajpheart.00049.2017 -
Obesity (Silver Spring, Md.) Jan 2011Obesity, especially when complicated with hypertension, is associated with structural and functional cardiac changes. Recent studies have focused on the prognostic...
Obesity, especially when complicated with hypertension, is associated with structural and functional cardiac changes. Recent studies have focused on the prognostic impact of the type of left ventricular (LV) geometric remodeling. This study looked at the prevalence and clinical correlates of LV geometric patterns and their relation to cardiac function in a sample of predominantly African-American (AA) youth. Echocardiographic data was collected on 213 obese (BMI of 36.53 ± 0.53 kg/m²) and 130 normal-weight subjects (BMI of 19.73 ± 0.21 kg/m²). The obese subjects had significantly higher LV mass index (LVMI; 49.6 ± 0.9 vs. 46.0 ± 1.0 g/m(2.7), P = 0.01), relative wall thickness (RWT; 0.45 ± 0.00 vs. 0.40 ± 0.00, P < 0.001), left atrial (LA) index (33.2 ± 0.7 vs. 23.5 ± 0.6 ml/m, P < 0.001), more abnormal diastolic function by tissue Doppler E/Ea septal (7.5 ± 0.14 vs. 6.5 ± 0.12 ms, P < 0.001), E/Ea lateral (5.7 ± 0.12 vs. 4.8 ± 0.1 ms, P < 0.001), myocardial performance index (MPI; 0.43 ± 0.00 vs. 0.38 ± 0.00, P < 0.001), and Doppler mitral EA ratio (2.0 ± 0.04 vs. 2.4 ± 0.07, P < 0.001) but similar systolic function. Concentric remodeling (CR) was the most prevalent pattern noted in the obese group and concentric hypertrophy (CH) in the obese and hypertensive group. Obesity, hypertension, and CH were independent predictor of diastolic dysfunction. Systolic (SBP) and diastolic blood pressures (DBP) were the prime mediators for CH whereas obesity and diastolic blood pressure were predictors of CR. No significant association was observed between the geometric patterns and systolic function. Tracking LV hypertrophy (LVH) status and geometric adaptations in obesity may be prognostic tools for assessing cardiac risk and therapeutic end points with weight loss.
Topics: Adolescent; Blood Pressure; Child; Echocardiography; Female; Heart Ventricles; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Obesity; Odds Ratio; Prognosis; Risk Factors; Ventricular Dysfunction, Left; Ventricular Remodeling
PubMed: 20559301
DOI: 10.1038/oby.2010.134 -
The International Journal of... Apr 2010Methods to index left ventricular (LV) mass, measured by cardiovascular magnetic resonance (CMR), for body size have not been investigated. The purposes of this study...
Methods to index left ventricular (LV) mass, measured by cardiovascular magnetic resonance (CMR), for body size have not been investigated. The purposes of this study were to develop allometric indices for LV mass measured by CMR and compare estimates of the prevalence and predictive value of LV hypertrophy defined by a new allometric height-weight index, LV mass/body surface area (BSA), height indices (a new allometric height index; and previously derived indices from echocardiographic measurements: LV mass/height(2), LV mass/height(2.7)), and non-indexed LV mass. 5,004 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with CMR measurements of LV mass and no clinical cardiovascular disease at baseline were followed for a median of 4.1 years. The new indices and limits for hypertrophy (95th percentile) were derived from 822 normal-weight, normotensive, non-diabetic MESA participants. 107 events (coronary heart disease or stroke) were observed. The estimated prevalence of hypertrophy at baseline and hazard ratio for event associated with hypertrophy were 8% and 2.4 with the new allometric height-weight index, 11% and 2.2 with LV mass/BSA, 23-24% and 2.0-2.1 with height indices, and 20% and 1.7 with non-indexed LV mass. A statistically significant difference was detected between the hazard ratios based on the new height-weight index and non-indexed LV mass. The prevalence of hypertrophy is higher for indices that do not account for weight. The predictive value of hypertrophy is significantly better with the new allometric height-weight index than with non-indexed LV mass and may be better than indices without weight.
Topics: Aged; Anthropometry; Body Height; Body Surface Area; Body Weight; Female; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Linear Models; Magnetic Resonance Imaging, Cine; Male; Middle Aged; Predictive Value of Tests; Prevalence; Severity of Illness Index; Ultrasonography; United States
PubMed: 20107905
DOI: 10.1007/s10554-010-9584-5