Development Of Diastolic Heart Failure Research Articles

The Relationship of Endothelial Dysfunction with the Development of Diastolic Heart Failure in Patients with Hypertension

Aim . To identify genetic predictors of diastolic dysfunction and signs of endothelial dysfunction in relation to indicators of left ventricular myocardial deformity in patients with hypertension. Material and methods . The study included 74 patients (38 women and 36 men) with hypertension 1-2 stages observed in the cardiology department of the Road clinical hospital at Chita II station. The mean age of patients was 32±9.4 years. Circulating endothelial cells (CEC) were determined by flow cytometry with BT 5000 device and antibodies to CD146+, CD45. Besides, 7AAD ion dye was used to detect living and dead endothelial cells. The number of CD146+, CD45 cells per 500000 blood cells was determined. Changes in CEC, Living/Dead CEC were studied. The data was processed using CXP Cytometer and Kaluza programs. The standard echocardiography, Doppler echocardiography and tissue Doppler echocardiography were used. Frequency distribution of alleles and genotypes: 1 mutation nitric oxide synthase 3 gene NOS3 -786 T>C; ( С -786 Т ) in relation to indicators of left ventricular myocardial deformity was analyzed in hypertensive patients with or without diastolic dysfunction as well as in the control group. Polymerase chain reaction with detection of amplification product in real time (RCR-rt) or electrophoresis in agarose gel on genomic DNA of peripheral blood leukocytes were used for studying gene mutations. Results . Development of diastolic dysfunction in hypertensive patients enhanced with the carrier of the genotype NOS3 -786 CC ( р =0.01 2, x 2 =1 2.53), endothelial dysfunction was manifested by an increase in the number of circulating endotheliocytes and was associated with a decrease in global longitudinal deformation of the left ventricle. Conclusion . Endothelial dysfunction in patients with hypertension is associated with a violation of global longitudinal deformation; and in patients with diastolic dysfunction these abnormalities are more pronounced than in patients without diastolic dysfunction.

Left atrial dysfunction in sickle cell anemia is associated with diffuse myocardial fibrosis, increased right ventricular pressure and reduced exercise capacity

Increased extracellular volume (ECV) by CMR is a marker of interstitial myocardial fibrosis and is associated with diastolic dysfunction in sickle cell anemia (SCA). Left atrial (LA) dysfunction and stiffness contribute to the development of diastolic heart failure in other settings. We aimed to evaluate LA function and stiffness associations with ECV, tricuspid regurgitation jet velocity (TRV) and exercise abnormalities in SCA. In a prospective study, individuals with SCA underwent CMR, echocardiography and exercise test. ECV was measured using MOLLI sequence. Atrial strain was studied in the 4- and 2-chamber views. LA stiffness was calculated as the ratio of echocardiographic E/e’-to-LA reservoir strain. Twenty-four participants with SCA were included (median age 20 years). ECV was increased in participant with SCA compared to our lab normal values (mean 0.44 ± 0.08 vs 0.26 ± 0.02, P < 0.0001). Six (25%) had LA LGE. ECV positively correlated with LA stiffness (r = 0.45, p = 0.04). There was a negative correlation between LA stiffness and %predicted VO2 (r = −0.50, p = 0.04). LA stiffness was moderately associated with increased TRV (r = 0.55, p < 0.005). LA stiffness is associated with ECV, exercise impairment and increased TRV. This study sheds insights on the interaction between LA function, RV hypertension, and myocardial fibrosis in SCA.

System of diagnosis of predisposition to the formation of diastolic heart failure in patients with anthracosilicosis and hypertension

Introduction. Anthracosilicosis (AS) is a serious and common occupational disease of workers in the coal industry, and among somatic diseases in miners more oft en than in the General population, there is an arterial hypertension (AH). One of the complications of such diseases is the development of chronic heart failure, and diastolic heart failure precedes the reduction of contractile function.The aim of the studywas to develop a system of diagnosis of predisposition to the formation of diastolic heart failure in patients with AS and AH.Materials and methods.71 miners with AC in combination with AH aged 40 to 54 years with preserved systolic function of the left ventricle (LV) were examined. Determined by: the presence of diastolic dysfunction of the ventricles, the presence and degree of respiratory failure, obesity, blood group AB0, MN and Rh, mass index left ventricular, thickness of the interventricular septum, posterior wall of LV anterior wall of right ventricle, index of relative wall thickness of LV and the average pressure in the pulmonary artery.Results.The higher the detection rate of this complication in the combination of AS and AG in patients with respiratory failure, obesity, with an increased index of myocardial mass of left ventricle, index of relative wall thickness of LV sphericity index, thickening of the walls of the ventricles, increased pressure in the pulmonary artery, having blood group 0 (I), B (III), MM, NN, Rh-, R+. Th e method of predicting the development of diastolic heart failure is as follows: the survey is carried out once, 10 of the above markers are determined, the data are analyzed using a prognostic table.Conclusions.With the help of the proposed method of predicting the development of diastolic heart failure in miners with AS and AH, it is possible to quickly and with litt le material cost to identify a group of people with a high risk of developing this complication.

Genetic predictors of chronic heart failure in obese patients

BACKGROUND: the study of molecular genetic markers and pathogenetic mechanisms of neurohormonal activation, as well as their importance in the formation of heart failure in obesity, is an urgent problem of modern medicine, the solution of which will allow effective prevention of cardiovascular complications, optimize treatment and improve the prognosis of obese patients.&#x0D; AIMS: search for genetic markers presumably involved in the pathogenesis of secondary diastolic heart failure in patients with obesity.&#x0D; MATERIALS AND METHODS: PCR-diagnostics of whole blood of 104 patients with obesity was carried out, which were divided into 2 groups, depending on the presence of diastolic heart failure. The following candidate genes were analyzed: angiotensinogen AGT gene (C521T and T704C), angiotensin II receptor gene of the first type AGTR1 (A1166C), angiotensin II receptor gene of the second type AGTR2 (G1675A), aldosterone synthase gene CYP11B2 (C (-344) T).&#x0D; RESULTS: It is shown that the development of secondary diastolic heart failure in obese individuals of both sexes is associated with the mutation of the aldosterone synthase gene CYP11B2, namely, with the replacement of the C allele at the -344 position by the T allele and the presence of the T / T genotype. The relative risk of developing the disease with the T / T genotype was 5.93 times higher in men (p = 0.008) and 4.57 times in women (p = 0.014). For men, the mutation of the angiotensinogen AGT gene, namely the replacement of the allele C at position 521 by the T allele, is important. At the same time, the relative risk of development of SDS in the T / T genotype is increased by 4.26 times (p = 0.039). Mutations of the genes of the angiotensin II receptor of the first type AGTR1 (A1166C) and the angiotensin II receptor of the second type AGTR2 (G1675A) are not associated with the development of diastolic heart failure in obese patients.&#x0D; CONCLUSIONS: The data presented can be used to stratify the risk of secondary heart failure in obese individuals.

Serum vitamin D, intact parathyroid hormone, and Fetuin A concentrations were associated with geriatric sarcopenia and cardiac hypertrophy

With aging, intact parathyroid hormone (iPTH) increases. It plays a crucial role in left ventricular hypertrophy (LVH). Also, 25-hydroxy vitamin D (Vit-D) and iPTH have been observed to be determinants of muscle wasting known as sarcopenia. Fetuin A (FetA), a systemic calcification inhibitor, involves in the development of diastolic heart failure. Hence, we hypothesized that the interplay among FetA, Vit-D and iPTH may contribute to sarcopenic LVH among the elders. We analyzed a database from the Tianliao Old People study with 541 elders (≥65 years) in a Taiwan’s suburban community. After excluding patients with renal function impairment, 120/449 (26.7%) patients were diagnosed with sarcopenia. Sarcopenic patients had lower serum Vit-D levels but higher FetA as well as iPTH. Notably, sarcopenic patients with LVH had significantly lower FetA and higher iPTH levels. In multivariate logistic regression analysis, only the increase in iPTH was independently associated with sarcopenic LVH (Odds ratio: 1.05; confidence interval: 1.03–1.08, p = 0.005). Using iPTH >52.3 ng/l as a cutoff point, the sensitivity and specificity was 66% and 84%, respectively. In conclusion, FetA, Vit-D, and iPTH levels were all associated with sarcopenia in this geriatric population. Among them, iPTH specifically indicates patients with sarcopenic LVH.

LBOS 02-03 THE INFILTRATING MACROPHAGE-SECRETED GALECTIN-3 PLAYS AN ESSENTIAL ROLE IN CARDIAC FIBROSIS AND DIASTOLIC FUNCTION IN MURINE PRESSURE-OVERLOAD MODEL

Objective: Cardiac fibrosis is the major pathophysiological process, contributing to the development of diastolic heart failure. We examine the role of macrophage-derived galectin-3 (gal-3) in cardiac fibrosis and diastolic function in response to transverse aortic constriction (TAC). Design and method: wild-type (WT) and gal-3 knock-out (KO) mice subjected to TAC; immunohistochemistry for myocardial macrophage infiltration,gal-3,and CTGF (connective tissue growth factor) expression; picrosirius red stain for myocardial fibrosis; FACS flow- cytometry for defining the origin of myocardial macrophages. MTT and Brdu incorporation for cell proliferation; flow-cytometry for cell differentiation; co-immunoprecipitation and confocal microscopy for lectin-carbohydrate interaction and co-localization respectively; echocardiography for left ventricular function. Results: WT mice after TAC showed significant increase of myocardial macrophage infiltration, gal-3 and CTGF expression, fibroblast proliferation/differentiation, and interstitial fibrosis leading to diastolic dysfunction, compared with controls (n = 10, p < 0.01). FACS flow-cytometry further identified that the increased myocardial macrophage population contains predominantly MHC-IIlow CCR2+ monocytes and MHC-IIhigh CCR2+ monocyte-derived macrophages. Macrophage depletion or gal-3 Knock-out mice markedly suppressed myocardial fibrosis. Re-administration of macrophages restored the fibrosis. In in-vitro, confocal microscopy and co-immunoprecipitation confirmed co-localization and gal-3-EGFR interaction on cell membrane. Treatment with recombinant gal-3 increased EGFR and downstream ERK phosphorylation, and CTGF expression in wild-type or gal-3 knock-down fibroblasts. Moreover, using MTT and Brdu incorporation assays, addition of gal-3, or macrophage-derived supernatant, or co-culture with macrophages significantly promoted fibroblast proliferation via CTGF expression. Finally, administration of gal-3 neutralizing monoclonal antibody remarkably reversed the myocardial fibrosis and improved diastolic function. Conclusions: Pressure-overload promotes myocardial macrophage infiltration and the macrophage -secreted gal-3 cross-links with its glycoconjugate, EGFR, resulting in its autophosphorylation, activation of subsequent mitogenic ERK signaling, myocardial CTGF expression, fibroblast proliferation/differentiation, resulting in myocardial fibrosis and diastolic dysfunction. Our findings provide molecular basis for gal-3 as a promising therapeutic target in heart failure.

Abstract 13143: The Relationship Between Coronary Microvascular Dysfunction and Preclinical Left Ventricular Diastolic Dysfunction: Invasive Physiologic and Echocardiographic Study

Background: Microvascular dysfunction has been associated with the development of diastolic heart failure. We hypothesized that invasively assessed microvasculature is related to diastolic function as assessed by echocardiography, even before the development of diastolic heart failure. Methods: We prospectively enrolled 63 subjects with preserved ejection fraction (≥55%) and no heart failure symptoms. Coronary physiologic assessment, including fractional flow reserve (FFR), coronary flow reserve (CFR), and the index of microcirculatory resistance (IMR), was performed in the LAD. Coronary flow was assessed with a thermodilution method by obtaining a mean transit time (Tmn: an inverse correlate to absolute flow) at rest and hyperemia. IMR was measured as distal coronary pressure x hyperemic Tmn. Left ventricular diastolic function was evaluated by an echocardiographic parameter (E/e’) using the following criteria; normal E/e’&lt;8, intermediate 8&lt;E/e’&lt;15, and high E/e’&gt;15, where a higher value was correlated with diastolic dysfunction. Results: Mean age was 54.5±12.3 years. All subjects had no significant stenosis in the LAD (FFR: 0.87±0.05). Mean CFR and IMR were 4.4±1.9 and 18.2±8.3, respectively. CFR and IMR were not significantly different among the 3 E/e’ groups (ANOVA p=0.60 for CFR and p=0.14 for IMR). Conversely, both resting and hyperemic Tmn were significantly shorter in patients with a high E/e’ value than with a normal value (p=0.04 for resting Tmn and p=0.03 for hyperemic Tmn, Figure), suggesting that coronary flow both at rest and hyperemia increases along with the progression of diastolic dysfunction. Conclusions: In this preclinical population, invasively assessed microvascular function (CFR/IMR) is not associated with diastolic dysfunction, whereas both resting and hyperemic flow are increased in subjects with diastolic dysfunction. Future studies are warranted to test the prognostic value of increased coronary flow.

The Effect of Acute Allergic Reactions on Diastolic Heart Function

Diastolic heart failure is characterized by the presence of heart failure symptoms despite preserved systolic function. Cytokines released during allergic reactions may impair diastolic heart function, either through their direct toxic effects or by inducing coronary artery spasm. The purpose of this study was to examine the effects of acute allergic reactions on diastolic heart function. Fifty patients, randomly selected from those who were admitted to the emergency room between May 2010 and December 2010 with the complaints of rash and itching, and who were subsequently diagnosed with allergic reactions based on the clinical and laboratory findings, were included in the study as the allergy group. Thirty healthy volunteers, in whom the diagnosis of allergy was ruled out based on the clinical and laboratory data, were use as the control group. Diastolic heart functions were evaluated in patients presenting with allergic reaction as well as in control subjects. There was no significant difference between the two groups in terms of basal systolic functions, diameters of the cavities and wall thicknesses, and biochemical parameters. Color M mode flow progression velocities, E ratios, E/A ratios and mitral lateral annulus tissue Doppler velocities measured by echocardiography at Day 0 and Day 5 were significantly altered in the allergy group (p < 0.05). Impairment in diastolic functions was observed following acute allergic reactions. Acute allergic reactions could be a cause of mortality and morbidity if they lead to the development of diastolic heart failure.

(433) - Myeloperoxidase is Critically Linked to the Development of Diastolic Heart Failure Following Pressure Overload

(433) - Myeloperoxidase is Critically Linked to the Development of Diastolic Heart Failure Following Pressure Overload

CrossTalk proposal: The late sodium current is an important player in the development of diastolic heart failure (heart failure with a preserved ejection fraction)

Approximately half of all patients with heart failure have an ejection fraction greater than 40–50% and may be diagnosed as having Heart Failure with preserved Ejection Fraction (HFpEF). Diastolic dysfunction is central to the pathophysiology of HFpEF (Borlaug & Paulus, 2011), and describes the slowing of ventricular relaxation and increased diastolic stiffness which ultimately impairs ventricular filling. The mechanistic basis of this impairment is complex and not yet well understood. Structural remodelling undoubtedly plays an important role in increasing left ventricular stiffness. However, the acute worsening of diastolic dysfunction during stress or exercise characteristic of HFpEF suggests an important contribution from dynamic changes in left ventricular (LV) functional properties. Frequency-dependent elevation of diastolic tension and intracellular Ca2+ ([Ca2+]i) has been observed in cardiac muscle strips from patients with left ventricular hypertrophy and diastolic dysfunction, or heart failure (Sossalla et al. 2008; Selby et al. 2011), implying that dysregulation of [Ca2+]i homeostasis of the cardiomyocyte contributes to diastolic dysfunction. Intracellular Ca2+ regulation is closely linked to intracellular Na+ homeostasis, through the Na+–Ca2+ exchanger (NCX). Intracellular Na+ of cardiomyocytes from failing hearts is increased and associated with elevated diastolic tension (Pieske et al. 2002). An important mechanism underlying this observation may be an increase in the late sodium current (INa,L). The Na+ conductance responsible for rapid depolarization of cardiomyocytes does not completely inactivate during the action potential. (Noble & Noble, 2006; Maier, 2012) Some channels continue to conduct, or even reactivate at relatively positive membrane potentials during the plateau and repolarization phases. This is INa,L (Zaza et al. 2008). Consequently, about half of the myocyte Na+ entry occurs during the initial 2–3 ms, and about half during the remainder of the action potential (Makielski & Farley, 2006). At the molecular level, INa,L results from channel reopening during sustained depolarization by two different modes of gating: burst openings and late scattered openings (Maltsev & Undrovinas, 2008). As outlined in Fig. 1, increased Na+ entry through INa,L increases intracellular Na+ ([Na+]i), which reduces the driving force for extrusion of Ca2+ and favours Ca2+ influx via the Na+–Ca2+ exchanger (NCX). This leads to increased [Ca2+]i. Elevated [Ca2+]i eventually increases actin–myosin filament interaction during diastole and thus increases diastolic tension. This mechanism of Ca2+ overload has been demonstrated in numerous animal studies, and in strips of ventricular muscle or myocytes isolated from patients with failing hearts (Valdivia et al. 2005; Makielski & Farley, 2006; Maltsev & Undrovinas, 2008; Sossalla et al. 2008; Selby et al. 2011; Coppini et al. 2013). Further, specific augmentation of INa,L with the sea anemone toxin ATXII in isolated myocytes and perfused hearts results in Na+ and Ca2+ overload (Fraser et al. 2006; Sossalla et al. 2008) and impaired diastolic function. Diastolic dysfunction with preserved systolic function has also been described in LQT syndrome type 3 patients, where INa,L is enhanced due to a Na+ channel mutation (Moss et al. 2008; Hummel et al. 2013). Figure 1 A pathological enhanced INa,L contributes to Na+-dependent Ca2+ overload, diastolic dysfunction We propose that a pathological increase in Na+ influx through cardiac Na+ channels, specifically due to enhanced INa,L is a major contributor to Ca2+ overload and diastolic dysfunction in HFpEF. Key evidence to support this hypothesis is outlined below.

CrossTalk opposing view: The late sodium current is not an important player in the development of diastolic heart failure (heart failure with a preserved ejection fraction)

CrossTalk opposing view: The late sodium current is not an important player in the development of diastolic heart failure (heart failure with a preserved ejection fraction)

Relations of diabetes mellitus, microvascular reperfusion and left ventricular remodelling in patients with acute myocardial infarction treated with primary coronary intervention

The aim of our study was to determine the influence of diabetes mellitus (DM) on myocardial reperfusion and left ventricular (LV) remodelling in patients with an acute myocardial infarction undergoing primary percutaneous coronary intervention. The study population consisted of 218 patients with first anterior ST-segment elevation myocardial infarction (STEMI) successfully treated with primary coronary angioplasty. We evaluated microvascular reperfusion using angiographic (Myocardial Blush Grade [MBG]) as well as electrocardiographic methods (ST-segment resolution > 70%). LV remodelling was defined asan increase in end-diastolic volume ≥ 20%, based on repeated measurements in individual patients. The study population was divided into two groups according to the presence, n = 43 (20%), or absence, n = 175 (80%), of DM. Patients with DM showed a significantly higher rate of MBG ≤2 (45.7% vs. 62.8%, p = 0.04) and lower incidence of ST-segment resolution > 70% (48% vs. 18.6%, p = 0.0003) compared to non-diabetics. Despite a similar incidence of LV remodelling in DM and non-DM groups (30.2% vs. 22.4%, p = 0.27), echocardiographic features of diastolic impairment and overt symptoms of heart failure were significantly more frequent in diabetic patients (55.2% vs. 27.1%, p = 0.006 and 36.1% vs. 18.3%, p = 0.02, respectively) at six-month follow-up. Despite worse microvascular reperfusion in STEMI patients with diabetes, the incidence of LV remodelling was similar compared to non-DM patients. DM was associated with the development of diastolic heart failure.

Progression of Left Ventricular Diastolic Dysfunction in Ethnic Minorities

Approximately 50 % of heart failure cases are due to diastolic failure. Generally, it is thought that asymptomatic diastolic dysfunction precedes the development of diastolic heart failure, representing an ideal time for intervention. Previous studies have examined progression rates in non-minority populations only. To determine the rate of diastolic dysfunction progression and the associated risk factors in a predominately ethnic minority population. A retrospective cohort study of participants drawn from the echocardiogram database and Electronic Health Record (EHR) for an academic medical center. Individuals with 2 or more echocardiograms showing diastolic dysfunction during a six year study period (2006–2012) were selected. Change in diastolic function grade over time and risk factors associated with this change. During the six-year retrospective study period, 154 patients with 2 or more echocardiograms demonstrating diastolic dysfunction were reviewed; these represented 496 echocardiograms. The mean time between echocardiograms was 1.9 years. Mean age was 64.6 (±10.1) years,81 % were female, and average BMI was 30.5(±7.4). The majority of subjects had Grade I diastolic dysfunction at the initial examination (87.7 % (n = 135)); 9 % (n = 14) had Grade II, and 3 % (n = 5) had Grade III. Approximately 27.9 % (n = 43) of the study cohort demonstrated overall worsening grade of diastolic dysfunction over time. Diastolic dysfunction grade was unchanged in 62 %(n = 96), improved in 9.7 % (n = 14), and worsened then improved in 0.7 % (n = 1). Our study showed a slightly higher rate of diastolic dysfunction progression in this predominately ethnic minority population. This is consistent with a previous study in a non-minority population demonstrating the progressive nature of diastolic dysfunction over time.Understanding the role of cardiovascular disease risk factors in accelerating progression rates from asymptomatic diastolic dysfunction to symptomatic stages is paramount to optimize intervention strategies.

Relationship between myocardial scar and hypertrophy by LGE CMR in hypertrophic cardiomyopathy patients with and without clinical events

Summary The purpose of this study was to investigate the relationship between the extent of hyperenhancement and left ventricle maximal wall thickness (mWT) detected by LGE CMR and clinical events of nonsustained ventricular tachycardia (NSVT), implantation of cardioverter defibrillator (ICD) or diastolic heart failure in HCM patients that underwent LGE CMR. Background Late gadolinium enhancement cardiac magnetic resonance (LGE CMR) imaging has been used to detect myocardial hypertrophy and scar/fibrosis in Hypertrophic cardiomyopathy (HCM) patients. The presence of hyperenhancement has been associated with progressive ventricular dilation, ventricular arrhythmias and clinical risk factors for sudden cardiac death. Methods Under IRB approved protocol a total of 82 HCM patients underwent LGE CMR images using a 2D PSIR TurboFLASH protocol after administration of 0.2 mmol of gadopentetate dimeglumine per kilogram of body weight. The presence of LGE was assessed using automated software: percentage of scar and maximal wall thickness were calculated. Percentage of scar was compared between patients with mWT <2.5 cm and ≥2.5cm The mean values of percentage scar and mean maximal wall thickness between patients with/ without clinical events (presence of NSVT, placement of ICD or development of diastolic heart failure) were compared. Results

Abstract 9013: Myeloperoxidase is Critically Linked to the Development of Diastolic Heart Failure Following Pressure Overload

Background: Plasma levels of the leukocyte derived enzyme myeloperoxidase (MPO) are elevated in patients with heart failure (HF). We have shown previously that MPO promotes vasoconstriction, leukocyte recruitment and myocardial fibrosis - suggesting that MPO may be mechanistically linked to the pathophysiology of HF. Here we assessed whether MPO is modulating systolic and diastolic myocardial performance in a pressure overload model. Methods and Results: C57Bl/6-Wild-type (WT) and MPO-deficient (Mpo-/-) mice were subjected to mild transverse aortic constriction (TAC, Δp max: 50 ±10 mmHg). After 6 weeks, echocardiography revealed significantly reduced left ventricular (LV) ejection fraction (EF) in TAC-treated animals as compared to sham operated controls. In vivo hemodynamic assessment of left ventricular function using pressure-volume loops revealed an upward shift of enddiastolic pressure volume relation (EDPVR) in both TAC groups as compared to sham animals (p&lt; 0.001). Of note WT-TAC revealed a significantly higher upward shift than Mpo-/- TAC (3.18 ±0.74 mmHg/µl vs. 1.17 ±0.17 mmHg/µl; n=8; p=0.02). Enddiastolic pressure was higher in WT-TAC as compared to Mpo-/- TAC (6.23 ±1.88 mmHg vs. 2.82 ±0.33 mmHg; n=8; p = 0.05). In WT-TAC heart weight and lung weight normalized on tibia length was significantly increased as compared to Mpo-/- TAC mice (15.21 ±0.67 mg/mm vs. 12.65 ±0.79 mg/mm; n=10; p&lt;0.02; respectively 20.15 ±2.65 mg/mm vs. 10.78 ±1.00 mg/mm; n=10; p=0.006). mRNA of matrix metalloproteinase 9 was increased in WT-TAC mice compared to Mpo-/- TAC (2.58 ±0,84 vs. 0,95 ±0,15, n=11; p=0,06). In accordance with this experimental observations MPO plasma levels of 5,000 patients enrolled in the Gutenberg Health Study were associated with left ventricular hypertrophy (median (IQR): 310pmol/l (240/384) vs. 297pmol/l (237/369); p=0.034). Conclusions: The current data reveal that MPO is critically linked to impaired diastolic compliance during pressure overload. This suggests that leukocyte activation in general and MPO release in particular is not only a prognostic marker in heart failure but evolves as an important pathophysiological link and potential pharmacological target in this disease.

Plasma biomarkers that reflect determinants of matrix composition identify the presence of left ventricular hypertrophy and diastolic heart failure.

Chronic pressure overload (such as arterial hypertension) may cause left ventricular (LV) remodeling, alterations in cardiac function, and the development of diastolic heart failure. Changes in the composition of the myocardial extracellular matrix may contribute to the development of pressure-overload-induced LV remodeling. We hypothesized that a specific pattern of plasma biomarker expression that reflected changes in these pathophysiological mechanisms would have diagnostic application to identify (1) patients who have development of LV hypertrophy (LVH) and (2) patients with LVH who have development of diastolic heart failure. Plasma concentration of 17 biomarkers (matrix metalloproteinase [MMP]-1, -2, -3, -7, -8, and -9; tissue inhibitors -1, -2, -3, and -4; N-terminal propeptide of brain natriuretic peptide (NT-proBNP); cardiotrophin; osteopontin; soluble receptor for advanced glycation end products; collagen I teleopeptide; collagen I NT-proBNP; and collagen III N-terminal propetide [PIIINP]), an echocardiogram, and 6-minute hall walk were performed on 241 referent control subjects, 144 patients with LVH but no evidence of heart failure, and 61 patients with LVH and diastolic heart failure (DHF). A plasma multibiomarker panel consisting of increased MMP-7, MMP-9, TIMP-1, PIIINP, and NT-proBNP predicted the presence of LVH with an area under the curve of 0.80. A plasma multibiomarker panel consisting of increased MMP-2, TIMP-4, PIIINP, and decreased MMP-8 predicted the presence of DHF with an area under the curve of 0.79. These multibiomarker panels performed better than any single biomarker including NT-proBNP and better than using clinical covariates alone (area under the curve, 0.73 for LVH and 0.68 for DHF). Plasma biomarkers reflecting changes in extracellular matrix fibrillar collagen homeostasis, combined into a multibiomarker panel, have discriminative value in identifying the presence of structural remodeling (LVH) and clinical disease (DHF).

Age- and Gender-Dependency of Left Ventricular Geometry Assessed with Real-Time Three-Dimensional Transthoracic Echocardiography

Aging and gender may affect left ventricular (LV) mechanics. The aim of this study was to determine the age and gender dependency of LV mechanical indices obtained from real-time three-dimensional echocardiography (RT3DE). RT3DE was performed in 280 healthy subjects (age range, 1-88 years; 137 men). From full-volume data sets, LV endocardial and epicardial borders were semiautomatically traced using quantitative software. LV volumes and corresponding long-axis diameter were measured throughout the cardiac cycle. Sphericity index was defined as the ratio of LV volume and spherical volume, calculated as 4/3 × π × (long-axis diameter/2)(3). LV mass was calculated as (LV epicardial volume - LV endocardial volume) × 1.05. The ratio of LV mass to LV volume was also calculated. The mean value of LV ejection fraction did not change with age. However, LV volumes, mass, sphericity index, and LV mass/volume ratio were altered by age: (1) sphericity index was highest in the first decade of age and then declined until the fifth decade, (2) LV mass/volume ratio significantly increased in older age, and (3) LV mass/volume ratio was significantly higher in aged women compared with age-matched men. Age has heterogeneous effects on LV shape and LV mass/volume ratio, potentially due to the growing process of myocardial fibers and the surrounding architecture in the younger population, as well as the aging process, with an increase in vascular stiffness and a loss of myocytes in older populations. Higher LV mass/volume ratios in older women might be a contributor to the preferential development of diastolic heart failure in this population.

Development of diastolic heart failure in a 6-year follow-up study in patients after acute myocarditis

BackgroundThe aim of this study was to analyse the long-term prognosis of patients with acute myocarditis (AMC) who had been discharged from hospital while having normal left ventricular (LV) function.Methods...

Left ventricular global systolic dysfunction has a significant role in the development of diastolic heart failure in patients with systemic hypertension

Regional left ventricular (LV) systolic dysfunction has been identified in diastolic heart failure (DHF). However, the relationship between regional or global LV systolic function and heart failure symptoms in DHF has not been evaluated in detail. The present study evaluates such relationships in patients with systemic hypertension (HT) and DHF. We assessed LV systolic and diastolic function in 220 consecutive patients with systemic HT and in 30 normal individuals (Control) using Doppler echocardiography. Patients with HT were assigned to groups with DHF, asymptomatic diastolic dysfunction (ADD) and no diastolic dysfunction (Simple HT). Ejection fraction in DHF was significantly decreased (63±8%) compared with the Control, Simple HT and ADD groups (67±5, 66±7 and 68±8%, respectively). Isovolumetric contraction time in DHF (70±30 msec) was significantly increased compared with those in the ADD, Simple HT and Control groups (31±17, 31±15 and 30±19 msec, respectively). Mitral annular systolic velocities were significantly decreased in the DHF and ADD groups (6.4±1.5 and 7.2±1.3 cm sec⁻¹, respectively) compared with those in the Simple HT and Control groups (8.5±1.8 and 8.4±3.0 cm sec⁻¹, respectively), and in the DHF group compared with the ADD group. LV global systolic dysfunction has a significant role in the development of heart failure symptoms associated with DHF in patients with systemic HT.

Left ventricular systolic function is abnormal in diastolic heart failure: Re-assessment of systolic function using cardiac time interval analysis

The purpose of this study was to re-assess the left ventricular (LV) systolic function in diastolic heart failure (DHF) using Doppler echocardiography. Systolic function in DHF is defined as the preserved LV ejection fraction (EF). EF may not fully reflect the systolic function in DHF, especially in the presence of abnormalities during the isovolumetric contraction time (ICT). We examined LV systolic and diastolic function in 80 consecutive patients with DHF, 30 patients with asymptomatic diastolic dysfunction (ADD), and 30 normal subjects (Control). The LV and left atrial volumes, LV EF, LV ICT, and isovolumetric relaxation time (IRT), early diastolic mitral flow velocity, systolic mitral annular velocity (S'), and early diastolic mitral annular velocity were obtained. LV ICT in DHF (69+/-30 ms) was significantly increased compared to those with ADD (37+/-23 ms) and Control (35+/-26 ms) (P<0.0001). ICT in ADD was equal to that in Control. The LV end-diastolic volume index in DHF (49+/-14 ml/m(2)) was significantly increased compared to those with ADD (42+/-12 ml/m(2)) and Control (43+/-8 ml/m(2)) (P<0.05). S' in DHF (5.9+/-1.4 cm/s) and ADD (6.7+/-1.1 cm/s) was significantly decreased compared to that in Control (8.7+/-2.5 cm/s). Our results revealed that the major differences between ADD and DHF were global and longitudinal LV systolic dysfunction and LV enlargement. This study suggests that LV systolic dysfunction plays an important role in the development of DHF.