Ventricular Diastolic Pressure Research Articles

The novel regulations of MEF2A, CAMKK2, CALM3, and TNNI3 in ventricular hypertrophy induced by arsenic exposure in rats.

Arsenic is a ubiquitous toxic compound that exists naturally in many sources such as soil, groundwater, and food; in which vast majority forms are arsenite (As(3+)) or arsenate (As(5+)). The mechanism of arsenic detoxification in humans still remains obscured. Epidemiologic studies documented that arsenic pollution caused black foot disease, cardiovascular diseases (hypertension, hypotension, cardiomyopathy), bladder cancer and skin cancer in many countries in which Taiwan is considered as high arsenic exposure country for long time ago. However, the effects of arsenic to cardiac functions still lacked of investigation while some studies mainly focus on inflammatory and cancer mechanisms. In the present study, we found cardiac hypertrophy signaling may be the most significant pathway for up regulated genes in arsenic exposed patients via bioinformatics approach. To verify our bioinformatics prediction, arsenic was fed orally to rats at different concentration based on previous studies in Taiwan. Using hemodynamic method as the main tool to measure the changes in blood pressure, left ventricular pressure and left ventricular contractility index, the findings suggest that highly exposure to arsenic lead to hypertension; elevated left ventricular diastolic pressure and alteration in cardiac contractility which are supposed to be the interaction between arsenic and cardiac nerves activity via the changing in calcium homeostasis. Collectively, based on our real-time PCR and western blot data strongly suggest that calcium homeostasis may also go through MEF2A, TNNI3, CAMKK2, CALM3 and cardiac hypertrophy relative signaling pathway.

Prosthetic mitral valve tamponade alternans

We wish to report an important clinical observation that combined several forms of imaging followed by pharmacological intervention that saved a patient froma potentially unnecessary surgical intervention. This was in a 65-year-old lady with previous Ultracor single tilting disc mitral valve replacement in 1996, systemic hypertension, chronic atrial fibrillation and epilepsy; who complained of worsening breathlessness. Clinically, she had physical signs of right heart failure. Trans-thoracic echocardiogram (TTE) showed mild left ventricular systolic impairment, dilated left atrium, significantly dilated right ventricle, moderate right ventricular systolic impairment, moderate rise of the systolic pulmonary artery pressure (55 mmHg), and a well-seated mechanical mitral valve prosthesis with no para-valvular leak. However, the Ultracor single-tilting-disc mechanical MV prosthesis was not opening on alternate cardiac cycles, Fig. 1. We did not agree with those who suspected a catastrophic malfunctioning of mechanical MV prosthesis and proposed a re-do operation. We noted that the function of the MV prosthesis was normal on alternate beats. We postulated that the intermittentmalfunction indicated a dynamic intermittent problem most likely related to the impact of the high right sided pressure on the diastolic pressure of the left ventricle which is preventing themechanicalMVprosthesis fromopeningeveryother beat. This is similar, though intermittent, to tamponade. We called that tamponade alternans of the MV prosthesis. We went on to confirm our hypothesis and performed fluoroscopy and an invasive simultaneous left and right heart catheter study [1]. Fluoroscopy confirmed the intermittent opening of the Ultracor singletilting-disc mechanical MV prosthesis every other beat (Fig. 2). The invasive studies showed severe pulsus alternans. The beats with the lower cardiac output were preceded by equalisation of right and left ventricular diastolic pressures (Fig. 2). The beats with the higher left ventricular output were preceded by a left ventricular end diastolic pressure higher than the right ventricular end diastolic pressure. The pulmonary artery pressure was 50/23 mm Hg with a mean of 38 mm Hg. The pulmonary capillary wedge pressure was high at 34/28 mm Hg. We had thus confirmed our hypothesis that the pulmonary hypertension is pushing the inter-ventricular septum paradoxically to the left (Fig. 2), and raising the left ventricular diastolic pressure to a level higher than the left atrial pressure as shown by changes in the diastolic left ventricular pressure curves (Fig. 2). This is preventing the opening of themitral valve. However, by the following cardiac cycle, the

Long-Term Risk to Develop Hypertension in Women With Former Preeclampsia: A Longitudinal Pilot Study.

Women with former preeclampsia (exPE) develop chronic hypertension 4 times more often than healthy parous controls. Women, destined to develop remote chronic hypertension, had increased left ventricular mass index (LVMI) and diastolic blood pressure (BP) prior to the onset of hypertension as compared to those remaining normotensive. However, longitudinal data on the progress of this increased LVMI in women destined to develop hypertension are lacking. We included 20 women with exPE and 8 parous controls. At both 1- and 14-year postpartum (pp), we performed cardiac ultrasound and determined circulating levels of the metabolic syndrome variables. Of 14-year pp, 7 (35%) former patients had developed chronic hypertension. We compared these 7 former patients with both the 13 former patients who remained normotensive and the 8 parous controls using the Mann-Whitney U test and Kruskal-Wallis analysis. Women with hypertensive exPE differed from their normotensive counterparts by a higher incidence of early-onset preeclampsia (PE) in their index pregnancy and a higher rate of recurrence in next pregnancies. At 1-year pp, they also had high/normal BP and higher fasting insulin levels. At 14 years pp, the relative left ventricular wall thickness was higher, and the E/A ratio was lower, in the hypertensive group relative to those remaining normotensive. Women with exPE are at increased risk of developing chronic hypertension, when (1) the PE in the index pregnancy had an early-onset and/or recurred in next pregnancies and (2) the 1-year pp. Blood pressure was high normal. We also noticed that at 14 years pp, the hypertensive group showed signs of concentric left ventricular remodeling along with a decreased E/A ratio.

Impact of Castration on Changes in Left Ventricular Diastolic Pressure–Volume Relations Induced by Chronic Adrenergic Stimulation in Rats

A reduced testosterone concentration characterizes heart failure and independently predicts outcomes. Although testosterone replacement therapy may have non cardiac-related therapeutic benefits in heart failure, whether reduced testosterone concentrations protect against adverse left ventricular remodeling (LV dilatation) is uncertain. We therefore evaluated whether surgical castration modifies LV dilatation after 6 months of daily injections of the β-adrenergic receptor (AR) agonist, isoproterenol (ISO) (0.015 mg·kg(-1)·d(-1)), to rats. The extent of LV dilatation and LV systolic chamber dysfunction were determined using both echocardiography and isolated perfused heart procedures. The extent of LV dilatation was determined from LV diastolic pressure-volume (P-V) relationships. As compared with the saline vehicle-treated group, after 6 months of β-AR activation in sham-castrated rats, a marked right shift in the LV diastolic P-V relationship was noted with an increased LV volume intercept at 0 mm Hg diastolic pressure (LV V(0) in milliliters) (ISO = 0.38 ± 0.02, saline vehicle = 0.30 ± 0.02, P < 0.05). However, chronic β-AR activation did not alter LV systolic chamber function either in vivo (LV endocardial fractional shortening, echocardiography) or ex vivo (LV end systolic elastance). Although castration decreased body weight, castration failed to modify the impact of ISO on the LV diastolic P-V relationships or the LV volume intercept at 0 mm Hg diastolic pressure (LV V(0) in milliliters) (castration ISO = 0.35 ± 0.02, castration saline vehicle = 0.27 ± 0.03, P < 0.05). In conclusion, castration does not influence the extent of LV dilatation induced by chronic adrenergic activation in an animal model, where adverse LV remodeling precedes LV systolic chamber dysfunction.

Increased basal and adenosine‐mediated coronary flow in ex vivo hearts from type I diabetic mice (1051.16)

Diabetes is known to cause morphological and functional changes in the cardiovascular system, resulting in abnormal responses to various stimuli such as adenosine. Our aim was to examine the functional changes in coronary flow (CF) to adenosine receptor (AR) agonists resulting from type I diabetes. Diabetes was induced in mice using streptozotocin (STZ, 10mg/Kg; 8 weeks) and concentration response curves to the non‐selective AR agonist NECA and to the A2A AR selective agonist (CGS‐21680; CGS) were performed in isolated perfused hearts from STZ and vehicle (C) group. Diabetes resulted in a decrease in heart weight (0.093g ± 0.002 in STZ vs. 0.117g ± 0.004 in C; p&lt;0.05), an increase in blood glucose level (510.8mg/dL ± 22.2 in STZ vs. 140.9mg/dL ± 9.4 in C; p&lt;0.05) and an increase in the basal coronary flow (21.6 ± 1.5 in STZ vs. 16.1 ± 0.6 in C; p&lt;0.05). Both NECA and CGS induced a concentration‐dependent increase in CF (ml.min‐1.mg‐1) which was significantly increased in STZ compared to C (NECA: Emax 39.8 ± 1.8 in STZ vs. 28.2 ± 0.7 in C; p&lt;0.05) (CGS; Emax 38.8 ± 1 in STZ vs. 28.3 ± 1.8 in C; p&lt;0.05). No significant differences were observed between the groups for changes in both heart rate and left ventricular diastolic pressure to both agonists. Our data suggest that STZ‐induced diabetes resulted in an increase in basal CF as well as increased vasodilatory response to adenosine agonists, probably by upregulating A2A receptor signaling.Grant Funding Source: Supported by HL 094447 and HL 027339

Pulmonary Hypertension in Heart Failure Preserved Ejection Fraction

An elevation of left ventricular diastolic and pulmonary venous pressure is typical of heart failure (HF) regardless of left ventricular (LV) ejection fraction. Normal left ventricular diastolic function keeps both pressures low (<12 mm Hg), although some increase may be observed during stress conditions, such as volume overload1 and exercise.2 When these changes occur within a range of transient periods and in a normal heart, they are well tolerated because of the pulmonary vasculature ability to recruit and distend the capillary network.3 Heart failure with preserved ejection fraction (HFpEF) is a condition presenting, by definition, with an impaired relaxation and stiffened myocardium, which is in part consequence of an increased load to the left ventricle attributable to the stiff arterial system and resulting in a well-defined ventricular–vascular uncoupling. These main hemodynamic alterations expose the lung vasculature to pressure-induced challenges whose most immediate acute threat is pulmonary edema.4 In the long term, the sustained backward hemodynamic transmission, along with the potential contribution of mitral insufficiency, increases the pulsatile loading on the right ventricle (RV)5 and triggers pulmonary hypertension (PH) development and symptom exacerbation.6 Thus, as a consequence of hemodynamic and functional perturbations, PH-HFpEF develops as a more advanced corollary of diastolic HF, leading to abnormal phenotypes of the lung microcirculation,7,8 the arterial system, and right heart function9–11 (Figure 1). Figure 1. From heart failure with preserved ejection fraction (HFpEF) to pulmonary hypertension (PH) HFpEF: hemodynamic components and pathophysiological correlates. In HFpEF, the central pathophysiological role is played by an impaired left ventricle (LV) filling mechanics that can arise both from intrinsic structural and molecular alterations in the LV (stiff heart) secondary to myocite hypertrophy, fibrosis, and impaired coronary reserve and as a consequence of an increased load to the heart …

Systolic and Diastolic Mechanics in Stress Cardiomyopathy

Stress cardiomyopathy (SCM) is a peculiar form of reversible left ventricular dysfunction seen predominantly in women and occurs in response to emotional or physical stress. Because dysfunction in SCM is reversible and that of acute myocardial infarction (MI) is not, we hypothesized that these fundamental mechanistic differences between SCM and MI would be associated with different systolic and diastolic properties. We examined 3 groups, all women: patients with SCM (n=24; mean age, 63±12 years), those with left anterior (LAD) ST-segment-elevation MI (n=36; mean age, 63±10 years), and referent control subjects (n=30; mean age, 62±8 years). All underwent angiography, ventriculography, and pressure measurements within 48 hours of presentation. Left ventricular volumes, diastolic pressures, and diastolic stiffness were higher in SCM and LAD MI patients than in control subjects but no different from each other. Similarly, left ventricular diastolic pressures and diastolic stiffness were elevated in the SCM and LAD MI groups compared with the control group. Left ventricular ejection fraction in SCM and LAD MI were 40.8±12.3% and 49.6±5.6%, respectively, versus 70.4±9.4% in control subjects (P<0.001), and stroke work less than half the value of control subjects. Indexes of contractility and ventricular-arterial coupling were similarly abnormal in SCM and LAD MI. SCM and LAD MI show severe diastolic dysfunction. At similar left ventricular volumes, their diastolic pressures are more than twice as high as in control subjects, and systolic dysfunction is equally reduced in SCM and LAD MI. Despite a completely different pathophysiology in terms of systolic and diastolic function, SCM is indistinguishable from acute LAD-territory MI.

Determination of the Effects of Digoxin on the Right Ventricular Function in Patients Undergoing Pneumonectomy

Introduction: Pneumonectomy is the standard treatment of lung cancer, even though patients should undergo several evaluations before surgery; deterioration of cardiopulmonary function after pulmonary resection is inevitable. We have evaluated the effects of digoxin on the improvement of right ventricular function and prevention of probable complications after lung resection surgery. Materials and Methods: All patients who were candidate for pneumonectomy or extensive lobectomy in Ghaem hospital from 2010 to 2012 were enrolled into this study and were divided into two groups randomly. The first group (group D) received digoxin during surgery and in the second group (group C) normal saline was administered as placebo. Echocardiographic evaluation of the patients was accomplished the day before and the day after surgery. Results: Among 20 patients in each group, male to female ratio was almost 2:1 and mean age was 63.8 (ranged 46-83 years). The most common cause of pneumonectomy was lung cancer. Comparison of the preoperative demographic variables, blood biochemistry, pulmonary function tests, echocardiographic and blood gas indexes showed no statistically significant differences between two groups. ,But postoperative evaluations showed a significant improvement in left ventricular ejection fraction in group D. Right ventricular systolic and diastolic diameters and pulmonary artery pressure were decreased significantly as well. Conclusion: According to our results, we suggest a single dose of digoxin during lung resection surgery to improve cardiac performance after pneumonectomy.

Circulation: Heart Failure Editors’ Picks

Summary : Lifelong exercise training maintains a youthful compliance of the left ventricle (LV), whereas a year of exercise training started later in life fails to reverse LV stiffening, possibly because of accumulation of irreversible advanced glycation end products. Alagebrium is a novel drug that breaks advanced glycation end product crosslinks and improves LV stiffness in aged animals. In this study, the authors prescribed alagebrium (200 mg daily) or placebo combined with aerobic exercise training or contact control in healthy, sedentary older individuals for 1 year. The authors evaluated overall cardiac function by the use of several modalities, including invasive pressure–volume measurements, exercise testing, and cardiac MRI before and after the training. To the authors’ knowledge, this is the first study to evaluate the effects of alagebrium and exercise training in healthy aged humans. After intervention, exercise training significantly increased exercise capacity, LV mass, and LV end-diastolic volume. Conversely, alagebrium had little effect on exercise capacity or LV geometry. However, alagebrium showed a modest improvement in LV stiffness compared with placebo. This favorable effect of alagebrium on LV stiffness was most prominent in individuals with combined alagebrium and exercise training. Conclusions : Alagebrium had no effect on hemodynamics, LV geometry, or exercise capacity in healthy, previously sedentary seniors. However, it did show a modestly favorable effect on age-associated LV stiffening.1 Summary : Maximum oxygen consumption (peak VO2) and efficiency of ventilation (VE) during exercise (VE/VCO2 slope) are known to stratify adults in heart failure for 1-year survival. On the basis of adult data, a recent American Heart Association scientific statement suggested that peak VO2<50% predicted for age and sex should be considered substantial impairment in exercise performance in children with heart disease and therefore a class I indication for heart transplant listing. This single-center study examined the association of …

Myocardial Expression Level of Neural Cell Adhesion Molecule Correlates With Reduced Left Ventricular Function in Human Cardiomyopathy

Recently, we screened for cardiac genes induced by metabolic stress and identified neural cell adhesion molecule (NCAM) as a candidate. This study aimed to clarify the expression pattern of NCAM in human cardiomyopathy. A total of 64 cardiac tissue samples of patients with dilated cardiomyopathy were dichotomized according to the immunohistochemically determined signal intensity of NCAM staining (NCAM-high and NCAM-low groups). Clinical and hemodynamic data of the patients were compared between the 2 groups. Fibrosis area, left ventricular end-diastolic volume index, and left ventricular diastolic pressure were greater in the NCAM-high group (22.8% versus 11.6%, P<0.05; 130.3±57.6 versus 104.8±31.7 mL/m(2), P<0.05; 14.3±8.0 versus 8.8±4.7 mm Hg, P<0.005; respectively). Incidence of cardiac death and admission for worsening heart failure was higher in the NCAM-high group during a follow-up of 6.3 years (log-rank P<0.05). Another 18 tissue samples were analyzed to determine the relationships between expression level of NCAM and major metabolic genes as well as hemodynamic parameters. The mRNA level of NCAM correlated with the serum (r=0.58; P=0.01) and mRNA levels (r=0.61; P=0.008) of brain-derived natriuretic peptides. It was also correlated with the mRNA levels of proliferator-activated receptor-γ coactivator-1 α (r=0.69; P=0.002) and the nuclear respiratory factor 1 (r=0.74; P<0.001). Expression of NCAM was associated with worsening hemodynamic parameters and major metabolic genes. Together with our previous findings, these data support the involvement of NCAM in left ventricular remodeling, revealing new insights into the pathophysiology of heart failure.

Estimation of maximum intraventricular pressure: a three-dimensional fluid–structure interaction model

BackgroundThe aim of this study was to propose a method to estimate the maximum pressure in the left ventricle (MPLV) for a healthy subject, based on cardiac outputs measured by echo-Doppler (non-invasive) and catheterization (invasive) techniques at rest and during exercise.MethodsBlood flow through aortic valve was measured by Doppler flow echocardiography. Aortic valve geometry was calculated by echocardiographic imaging. A Fluid–structure Interaction (FSI) simulation was performed, using an Arbitrary Lagrangian–Eulerian (ALE) mesh. Boundary conditions were defined as pressure loads on ventricular and aortic sides during ejection phase. The FSI simulation was used to determine a numerical relationship between the cardiac output to aortic diastolic and left ventricular pressures. This relationship enabled the prediction of pressure loads from cardiac outputs measured by invasive and non-invasive clinical methods.ResultsVentricular systolic pressure peak was calculated from cardiac output of Doppler, Fick oximetric and Thermodilution methods leading to a 22%, 18% and 24% increment throughout exercise, respectively. The mean gradients obtained from curves of ventricular systolic pressure based on Doppler, Fick oximetric and Thermodilution methods were 0.48, 0.41 and 0.56 mmHg/heart rate, respectively. Predicted Fick-MPLV differed by 4.7%, Thermodilution-MPLV by 30% and Doppler-MPLV by 12%, when compared to clinical reports.ConclusionsPreliminary results from one subject show results that are in the range of literature values. The method needs to be validated by further testing, including independent measurements of intraventricular pressure. Since flow depends on the pressure loads, measuring more accurate intraventricular pressures helps to understand the cardiac flow dynamics for better clinical diagnosis. Furthermore, the method is non-invasive, safe, cheap and more practical. As clinical Fick-measured values have been known to be more accurate, our Fick-based prediction could be the most applicable.

Management of Aortic Insufficiency in the Continuous Flow Left Ventricular Assist Device Population

With the current generation of continuous-flow (CF) left ventricular assist devices (LVADs), patients are able to be supported for longer periods of time. As a result, there has been increasing focus on long-term complications from prolonged mechanical circulatory support, such as acquired aortic insufficiency (AI). In the presence of an LVAD, AI leads to a blind circulatory loop, with a portion of LVAD output regurgitating through the aortic valve (AV) into the left ventricle and back again through the device, limiting effective forward flow and ultimately leading to organ malperfusion and increased left ventricular diastolic pressures. The AV also experiences abnormal biomechanics as a result of limited valve opening in the presence of a CF LVAD. Increased shear stress, elevated transvalvular pressure gradients, and decreased valve open time all contribute to acquired AI. The prognosis of moderate to severe AI in LVAD patients is generally poor and leads to a higher rate of AV replacement and potentially reduced survival. However, there are no evidence-based guidelines for management of this challenging population. In severe AI, experts generally advocate AV replacement or repair, while lesser degrees of AI can be managed medically and/or with adjustments in pump parameters.

Extent and severity of coronary artery disease by coronary CT angiography is associated with elevated left ventricular diastolic pressures and worsening diastolic function

BackgroundPatients with flow-limiting coronary stenoses exhibit elevated left ventricular end-diastolic pressure (LVEDP) and abnormal left ventricular (LV) relaxation. ObjectiveWe investigated the relationship of extent and severity of coronary artery disease (CAD) by coronary CT angiography (CTA) to LVEDP and measures of LV diastolic dysfunction. MethodsWe identified consecutive patients undergoing coronary CTA and transthoracic echocardiography who were assessed for diastolic function. CAD was evaluated on a per-patient, per-vessel, and per-segment basis for intraluminal diameter stenosis by using an 18-segment model (0 = none, 1 = 1%–49%, 2 = 50%–69%, and 3 = 70%–100%) and summed over segments to obtain overall coronary plaque burden (segment stenosis score [SSS]; maximum = 54). Transthoracic echocardiography evaluated mitral inflow E wave-to-A wave ratio, tissue Doppler early mitral annual tissue velocity axial excursion, stage of diastolic dysfunction, and LV dimensions and estimated LVEDP from the ratio of mitral inflow velocity to early mitral annular (medial) tissue velocity. ResultsFour hundred seventy-eight patients (57% women; mean age, 57.9 ± 14.6 years; 24.9% prior CAD) comprised the study population. Increasing per-patient maximal coronary stenosis, number of vessels with obstructive stenosis, and SSS were associated with increased LVEDP. The prevalence of advanced diastolic dysfunction increased with greater number of obstructive vessels. In multivariable analyses, SSS was associated with increased LVEDP (0.8 mm Hg per tertile increase in SSS, 0.5–1.1; P < .001); reduced E′ axial excursion (−0.3; 95% confidence interval [CI], −0.5 to −0.1; P = .001), increased LV mass index (1.6 g/m2 per tertile increase in SSS; P = .04), and increased relative wall thickness (0.005; 95% CI, 0.004–0.009; P = .03), with consistent relationships persisting even among persons with per-patient maximal stenosis <50% and LV ejection fraction ≥55%. ConclusionsExtent and severity of obstructive as well as nonobstructive CAD by coronary CTA are associated with increased LVEDP and measures of diastolic dysfunction.

Noninvasive estimation of pulmonary capillary wedge pressure using speckle tracking echocardiography in patients with preserved or reduced ejection fraction

Purpose: Echocardiographic parameters such as a ratio of early mitral inflow velocity (E) to atrial contraction flow velocity (A) and a ratio of E to mitral annular tissue velocity (e') were proposed to estimate left ventricular (LV) diastolic function and pulmonary capillary wedge pressure (PCWP). However, E/A and E/e' have limitations to use in various conditions. Noninvasive estimation of PCWP has not been elucidated. We have recently developed a novel index to estimate PCWP using left atrial (LA) emptying function (EF) and volume (LAV) assessed by speckle tracking echocardiography (STE) and named it kinetics-tracking (KT) index: log (active LAEF/ minimum LAV index). The estimated PCWP (ePCWP) was determined as 10.7 – 12.4 × KT index. The aim was to examine the usefulness of KT index in patients with preserved or reduced ejection fraction to estimate PCWP measured by cardiac catheterization. Methods: We measured phasic LAV and EF obtained from time-LA volume curves by STE during sinus rhythm in consecutive 128 patients (age 67±12, 80 men, 77 patients with LV ejection faction ≥55%) just before cardiac catheterization. Patients with atrial fibrillation, severe mitral regurgitation and mitral stenosis were excluded. LA volume and EF and E/e' were compared with PCWP measured by cardiac catheterization. Moreover, ePCWP estimated by 4 combinations of LA maximum or minimum volume and LA total or active EF was compared with PCWP by cardiac catheterization. Results: The maximum and minimum LAV index were correlated with PCWP (r=0.71 and r=0.78, respectively, p 15 mmHg were 95 and 88%, respectively (AUC = 0.97) using KT index of 17.8 as an optimal cutoff value. In multivariate regression analysis, only KT index was an independent parameter to estimate PCWP by cardiac catheterization in 128 subjects. Conclusions: For noninvasive estimation of LV diastolic function, the KT index is a novel and more accurate predictor of PCWP than LA function, volume solely or E/e'. KT index have an incremental value in routine clinical practice.

Can melatonin improve cardiac function in pulmonary arterial hypertension?

Background/hypothesis: Pulmonary arterial hypertension (PAH) is a disorder characterized by elevated pulmonary arterial pressure which leads to cardiac hypertrophy and dysfunction. Current treatments have marginal impact and additional therapies are required. Melatonin is a natural product shown to be cardioprotective against hypertension and myocardial ischemia. We propose that melatonin treatment may be cardioprotective in a model of monocrotaline (MCT) induced PAH. Materials and methods: Male long Evans rats (150-175g) were injected with MCT (80mg/kg) which induced PAH after 28 days. Melatonin was added daily in the drinking water (75ng/L, 4x106ng/L or 6x106ng/L) for the 28 days (n>4 per group). Cardiac hypertrophy was confirmed with a ratio of the right ventricle weight over heart weight (RVW/HW). Cardiac functional parameters were assessed at 0 and 28 days using isolated heart perfusion and/or echocardiography. These parameters included right ventricular systolic (SP) and diastolic pressure (DP), ejection fraction (EF) and fractional shortening (FS). Results: 28 days after a MCT injection, RVW/HW was increased and FS was reduced compared to the control group (28.2%±2.7 vs. 61.0%±2.9, p<0.0002). At the dose of 75ng/L, melatonin further decreased FS (21.0%± 0.1, p<0.04 vs MCT alone). In contrast, melatonin given at the dose of 4x106ng/L and 6x106ng/L improved FS (48.7%± 2.1% and 44.3%±1.7, respectively, p<0.002 vs MCT alone). Conclusions: In an animal model of pulmonary arterial hypertension, our data suggest that melatonin improves cardiac function in a dose-dependent manner. Melatonin may represent a novel therapeutic approach in the treatment of PAH.

GW24-e2910 Research on Effects of Qishen Granule on Hemodynamics in Mini Pigs with Cardiac Functional Insufficiency and Qi-deficiency and Blood Stasis Syndrome Induced by Ameroid Constricting Ring

ObjectivesTo explore the effects of Qishen Granule, a compound Chinese herbal medicine, on hemodynamics in a mini pig model of cardiac functional insufficiency and qi-deficiency and blood stasis syndrome induced...

Left ventricular end-diastolic pressure affects measurement of fractional flow reserve

Fractional flow reserve (FFR), the hyperemic ratio of distal (Pd) to proximal (Pa) coronary pressure, is used to identify the need for coronary revascularization. Changes in left ventricular end-diastolic pressure (LVEDP) might affect measurements of FFR. LVEDP was recorded simultaneously with Pd and Pa during conventional FFR measurement as well as during additional infusion of nitroprusside. The relationship between LVEDP, Pa, and FFR was assessed using linear mixed models. Prospectively collected data for 528 cardiac cycles from 20 coronary arteries in 17 patients were analyzed. Baseline median Pa, Pd, FFR, and LVEDP were 73 mmHg, 49 mmHg, 0.69, and 18 mmHg, respectively. FFR<0.80 was present in 14 arteries (70%). With nitroprusside median Pa, Pd, FFR, and LVEDP were 61 mmHg, 42 mmHg, 0.68, and 12 mmHg, respectively. In a multivariable model for the entire population LVEDP was positively associated with FFR such that FFR increased by 0.008 for every 1-mmHg increase in LVEDP (beta=0.008; P<0.001), an association that was greater in obstructed arteries with FFR<0.80 (beta=0.01; P<0.001). Pa did not directly affect FFR in the multivariable model, but an interaction between LVEDP and Pa determined that LVEDP's effect on FFR is greater at lower Pa. LVEDP was positively associated with FFR. The association was greater in obstructive disease (FFR<0.80) and at lower Pa. These findings have implications for the use of FFR to guide revascularization in patients with heart failure. The impact of left ventricular diastolic pressure on measurement of fractional flow reserve (FFR) is not well described. We present a hemodynamic study of the issue, concluding that increasing left ventricular diastolic pressure can increase measurements of FFR, particularly in patients with FFR<0.80 and lower blood pressure.

Hypertension After Preeclampsia Is Preceded by Changes in Cardiac Structure and Function

Preeclampsia is associated with a 4-fold higher risk for developing remote chronic hypertension. Preeclampsia is accompanied by left ventricular hypertrophy and decreased diastolic function, which may or may not resolve postpartum. We tested the hypothesis that increased measures of cardiac geometry and decreased cardiac function persisting for ≥ 6 months postpartum in normotensive women with a history of preeclampsia precede the development of later chronic hypertension. Formerly preeclamptic women (n=652) underwent echocardiography at 9 months (range, 6-19) postpartum. We excluded women with preexisting hypertension (n=42), hypertension at the postpartum screening (n=133), and those that did not return any checklist (n=128). Eventually, 349 women were included. Remote health was evaluated by a biennially checklist. We used Cox regression for analysis. Twenty-seven (8%) normotensive women had developed chronic hypertension during a medium follow-up period of 6 years. At screening they differed from their counterparts who remained normotensive by hazard ratio for left ventricular mass index (1.11; 95% confidence interval [CI], 1.03-1.18), diastolic blood pressure (1.13; 95% CI, 1.06-1.20), systolic blood pressure (1.07; 95% CI, 1.02-1.11), mean arterial pressure (1.11; 95% CI, 1.05-1.18), heart rate (1.05; 95% CI, 1.01-1.10), and E/A ratio (0.22; 95% CI, 0.06-0.85). Backward stepwise analysis showed independent hazard ratio for left ventricular mass index and diastolic blood pressure 1.08 (95% CI, 1.01-1.16) and 1.13 (95% CI, 1.06-1.21), respectively. In conclusion, the development of later chronic hypertension in initially normotensive formerly preeclamptic women is preceded by increased left ventricular mass index and diastolic blood pressure at postpartum screening.

In‐treatment HDL cholesterol levels and development of new diabetes mellitus in hypertensive patients: The LIFE Study

Although hypertensive patients with low baseline HDL cholesterol levels have a higher incidence of diabetes mellitus, whether changing levels of HDL over time are more strongly related to the risk of new diabetes in hypertensive patients has not been examined. Incident diabetes mellitus was examined in relation to baseline and in-treatment HDL levels in 7485 hypertensive patients with no history of diabetes randomly assigned to losartan- or atenolol-based treatment. During 4.7 ± 1.2 years follow-up, 520 patients (6.9%) developed new diabetes. In univariate Cox analyses, compared with the highest quartile of HDL levels (> 1.78 mmol/l), baseline and in-treatment HDL in the lowest quartile (< 1.21 mmol/l) identified patients with > 5-fold and > 9 fold higher risks of new diabetes, respectively; patients with baseline or in-treatment HDL in the 2nd and 3rd quartiles had intermediate risk of diabetes. In multivariable Cox analyses, adjusting for randomized treatment, age, sex, race, prior anti-hypertensive therapy, baseline uric acid, serum creatinine and glucose entered as standard covariates, and in-treatment non-HDL cholesterol, Cornell product left ventricular hypertrophy, diastolic and systolic pressure, BMI, hydrochlorothiazide and statin use as time-varying covariates, the lowest quartile of in-treatment HDL remained associated with a nearly 9-fold increased risk of new diabetes (hazard ratio 8.7, 95% CI 5.0-15.2), whereas the risk of new diabetes was significantly attenuated for baseline HDL < 1.21 mmol/l (hazard ratio 3.9, 95% CI 2.8-5.4). Lower in-treatment HDL is more strongly associated with increased risk of new diabetes than baseline HDL level.

Non‐surgical periodontal treatment reduces cardiovascular risk in refractory hypertensive patients: a pilot study

To evaluate the effects of non-surgical periodontal treatment on left ventricular mass (LVM), arterial stiffness, systolic and diastolic blood pressure and plasma levels of inflammatory markers (C-reactive protein (CRP), fibrinogen and interleukin-6) in refractory hypertension patients. This interventional prospective cohort pilot study included 26 patients (53.6±8.0years old) diagnosed with refractory hypertension and generalized chronic periodontitis. Subjects received non-surgical periodontal treatment according to their needs. Plasma levels of systemic inflammation (CRP; fibrinogen and interleukin-6) and established cardiovascular risk factors [systolic and diastolic blood pressure (SBP and DBP), left ventricular mass (LVM) and arterial stiffness] were assessed at three time points (baseline, 3months after baseline and 6months after periodontal therapy). Periodontal therapy significantly reduced all cardiovascular risk markers evaluated. Median values of SBP and DBP were reduced by 12.5mmHg and 10.0mmHg, respectively, whereas left ventricular mass (LVM) reduced by 12.9g and pulse wave velocity reduced by 0.9m/s (p<0.01). Levels of CRP, IL-6 and fibrinogen lowered by 0.5mg/dl, 1.4pg/dl and 37.5mg/dl (p<0.01), respectively, 6months after periodontal therapy. Periodontal therapy significantly reduced levels of CRP, IL-6, fibrinogen, blood pressure, LVM and arterial stiffness, lowering cardiovascular risk in refractory hypertensive patients.