Left Ventricular Diastolic Pressure Research Articles

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.

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 …

Early diagnosis of LV diastolic dysfunction for diabetic patients

Left ventricular diastolic dysfunction precipitates to cardiac disorders like myocardial infarction, left ventricular hypertrophy and cardiac artery disease. Raised diastolic left ventricular pressure results in inefficient pumping of the oxygenated blood, leads to LVDD modifying the heart structurally and functionally. An index computed from R-R interval, derived from two-lead, 3–5 minute ECG samples, provides a guideline to the echo-cardiologist. The index values of the diabetic subjects with LVDD are observed to be the lowest, that of diabetic subjects without LVDD are lower than the control group. The index proves to be early, safe, deployable, cost-effective and non-invasive confirmative diagnostic tool.

Mechanoelectric feedback does not contribute to the Frank-Starling relation in the rat and guinea pig heart

Mechanoelectric feedback (MEF) is the process by which mechanical forces on the myocardium can alter its electrical properties. The effect can be large enough to induce ectopic beats or fibrillation. However, the role of MEF at physiological levels of mechanical stress is not clear. We have investigated alteration in action potential morphology in rat and guinea pig ventricle and in rat atrial tissue at levels of stretch near the plateau of the Frank-Starling curve. Stretch of &gt;100 mm.Hg End Diastolic Left Ventricular Pressure (EDLVP) or rapidly applied stretch (EDLVP increased by 25 mm.Hg within 100 ms) often triggered ectopic beats in isolated rat and guinea-pig hearts. However, ventricular epicardial monophasic action potentials (MAPs) recorded during stretch to EDLVP up to 30 mm. Hg showed no consistent changes in action potential duration (at APD20, APD50 or APD80) in either species. MAP recording detected APD prolongation with very small concentrations of 4-AP (10 μM), confirming the discrimination of the recording technique. In isolated rat atrial strips, no changes in intracellular action potential morphology or membrane potential were seen when stretched to levels producing an optimum increase in contractility. We conclude that alteration in action potential morphology with stretch does not contribute to the Frank-Starling relation in ventricle of rat or guinea-pig isolated heart, or in rat atrial tissue.

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.

Unsuccessful treatment of accelerated hypertension and persistent hyperkinetic state in a haemodialysed patient with high-output arteriovenous fistula

The case we describe concerns a rapid progression of heart failure (HF) in a patient with hypertension crises (HC), haemodialysed (HD) with the use of a high-output arteriovenous fistula (AVF). The 48-year-old male with a body mass index of 19.27 kg/m2, renal insufficiency due to glomerulonephritis, treated with HD for two years (3 × 4.0 h/week), and with uncontrolled hypertension was admitted to the Military Institute of Medicine. On examination, reduced exercise tolerance, paroxysmal nocturnal dyspnoea and blood pressure (BP) 190/90 mm Hg were found. Laboratory tests revealed NT-pro B-type natriuretic peptide 302,009.0 pg/mL (n < 300.0). Echocardiography (ECHO) showed left ventricular (LV) hypertrophy (LV mass index [LVMI] 345.81 g/m2), enlarged LV diastolic diameter [LVDD] 7.15 cm), with slightly decreased ejection fraction (EF 49%), Doppler signs of elevated cardiac output (CO 15.05 L/min; cardiac index (CI) 8.91 L/min/m2), and pseudonormalised pattern of mitral inflow with elevated LV diastolic pressure (E/E’ 31). In ultrasonographic examination of left shoulder AVF, an aneurysmal expansion of the lumen from 5.5 mm to 35 mm (Fig. 1), and significantly increased flow up to 2,532 mL/min (Fig. 2) were detected. Cardiopulmonary recirculation rate (CPR) was 0.17. Computed tomography excluded renal artery stenosis. In polysomnography, heavy central apnoea with an apnoea/hypopnoea index of 35.4/h was found. In 48-h ambulatory BP monitoring (ABPM), BP was 162/95 mm Hg. Treatment of sleep apnoea was implemented by a continuous positive airway pressure device, but this did not improve BP control. Upon discharge from hospital, the patient was overtreated with eight hypotensive drugs. After a month, HC occurred (BP 220/120 mm Hg) associated with acute coronary syndrome without ST-segment elevation. Coronarography found non-obstructive atherosclerotic plaques. Because of the suspicion of hyperkinetic state related to a lack of BP control, AVF was narrowed by implanting a polytetrafluorethylene graft of 4 mm diameter (Fig. 3). Despite AVF flow being reduced to 1,400 mL/min, after two months another HC (BP 220/125 mm Hg) with pulmonary oedema was presented. The next HC took place three months later. Although ECHO showed features of LV hypertrophy regression (LVMI 335.62 g/m2), and significant decreases of CO (8.16 L/min) and CI (4.86 L/min/m2), a decrease of EF (40%) and an LV dilatation enlargement (LVDD 7.7 cm) were also observed. AVF flow increased up to 1,750 mL/min and significant CPR 0.21 was indicated. In 24-h ABPM, BP was 173/105 mm Hg. The hypotensive treatment used has been confirmed by experts and seems to be optimal and safe for the cardiovascular system. Probably, AVF banding was performed too late, and progression of HF and lack of BP control improvement were observed. In hyperkinetic AVF, blood flow exceeds 2,000 mL/min and CPR is over 0.2–0.3. Currently, in cases of difficulties in surgical AVF creation and the necessity of haemodialysotherapy termination as a result of a lack of vascular access, banding or closure of the AVF is a very rare event. However, in some cases, early ligation of AVF may be the only effective procedure, especially when there is rapid progression of HF.

Paravalvular aortic regurgitation as the reason for second CoreValve bioprosthesis implantation in a patient with native bicuspid valve

We present the case of a 70-year-old male patient who was admitted to our centre with severe symptomatic aortic stenosis. His medical history included: hypertension, stroke (1998 and 2013) with subsequent left-sided paraparesis and status after traumatic upper right limb amputation in his youth. Patient’s logistic EuroSCORE was 18.1%, EuroSCORE II 5.7% and the Society of Thoracic Surgeons Score 2.7%. Transthoracic echocardiography showed impaired left ventricular ejection fraction of 27%, mean aortic pressure gradient of 70.5 mm Hg, aortic valve area of 0.6 cm2, and peak velocity of 6.3 m/s. For precise aortic annulus measurement, transoesophageal echocardiography (TEE) and a computed tomography scan were performed and revealed a heavily calcified bicuspid valve with mean annulus diameter of 24 mm. Angiography demonstrated a significant lesion in the 3rd segment of right coronary artery (RCA). Due to the high operative risk, the patient was referred by the Heart Team for percutaneous coronary intervention of RCA and transcatheter aortic valve implantation (TAVI) via the femoral route (considering the absence of atherosclerotic lesions in ilio-femoral arteries). Native valve was predilated with a 22 mm Numed balloon catheteter (Fig. 1A). On the basis of pre-procedural imaging, a 29 mm Medtronic CoreValveTM bioprosthesis was implanted at the annulus level. However, control angio and TEE showed low implantation accompanied by significant paravalvular aortic regurgitation (Fig. 1B). Haemodynamic measurement also confirmed a suboptimal effect with low diastolic aortic pressure (DAP) and high left-ventricular end-diastolic pressure (LVEDP) (Fig. 2A). Therefore, the decision was made to implant a second bioprosthesis — another 29 mm CoreValve was placed and deployed 8–10 mm higher than the first one (Fig. 1C). Implantation of the second valve significantly decreased the magnitude of regurgitation from severe to no or mild, both in angiography and pressure recordings (Figs. 1D and 2A, respectively). It has been shown in several observational and randomised trials that even mild paravalvular regurgitation after TAVI is an independent predictor of long-term mortality. It is therefore of crucial importance to diagnose early and minimise the grade of regurgitation by post-dilatation or second valve deployment. This case demonstrates that apart from imaging modalities, direct pressure measurement is an easy, reliable and reproducible method of paravalvular leak detection. Recently, it has been shown in a non-selected population of TAVI procedures that pressure gradient DDAP-LVEDP is a powerful predictor of mortality.

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.

Preservation of myocardial contractile function by aminoguanidine, a nitric oxide synthase inhibitors, in a rat model of hemorrhagic shock

Myocardial contractile dysfunction plays a major role in the outcome of trauma patients. Nitric oxide (NO) has been shown to increase following haemorrhagic shock. Peroxynitrite which is produced by the reaction of NO with reactive oxygen species leads to nitrosative stress mediated organ injury and myocardial contractile dysfunction. Aminoguanidine is a selective inhibitor of inducible nitric oxide synthase (iNOS). The aim of this study was to determine the protective effects of inhibiting the production of NO using aminoguanidine (AG) on myocardial contractility, following hemorrhagic shock and resuscitation in rats. Male Sprague-Dawley rats were assigned to 3 experimental groups (n = 6 per group):1) Normotensive rats (N), 2) Hemorrhagic shock rats (HS), and 3) Hemorrhagic shock rats treated with AG 60 mg/kg AG intra-arterially (HS-AG). Rats were hemorrhaged over 60 minutes to reach a mean arterial blood pressure of 40 mmHg. Rats were treated with 1 ml of 60 mg/Kg AG intra-arterially after 60 minutes haemorrhagic shock,. Resuscitation was performed in vivo by the reinfusion of the shed blood for 30 minutes to restore normo-tension. Hearts were harvested and ex vivo perfused in the Langendorff System and myocardial function was determined by measuring the left ventricular end diastolic pressure (LVEDP) and left ventricular systolic pressure (LVSP). Left ventricular generated pressure (LVGP) and + dP/dt max was calculated. Hemorrhagic shock rats treated with AG exhibited a significant increase in left ventricular generated pressure LVGP (137.1 ± 9.4 mmHg) and + dP/dtmax (589.6 ± 110.7 mmHg/sec) compared with the untreated group (44.43 ± 20.18 mmHg, 289.8 ± 25.0 mmHg/sec). Treatment with AG protects the myocardium from post-resuscitation myocardial dysfunction.

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.

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.

Biomarkers of Diastolic Dysfunction and Myocardial Fibrosis: Application to Heart Failure with a Preserved Ejection Fraction

Comprehensive diagnostic criteria, accurate prognostic indicators, and effective treatment for patients with heart failure and a preserved ejection fraction (HFpEF) represent a critically important unmet need in cardiovascular medicine. Novel approaches to fill this unmet need are likely to be facilitated by targeting the underlying and unique pathophysiologic mechanisms that characterize patients with HFpEF. Two possible targets include hemodynamic overload evidenced by increased LV diastolic pressure (LVDP) and myocardial fibrosis evidenced by increased extracellular matrix fibrillar collagen. The measurement of LVDP and fibrosis generally requires either invasive procedures and/or complex and sophisticated imaging techniques. However, biomarkers measured in the plasma have been shown to accurately reflect changes in hemodynamic load and myocardial fibrosis and may have important application to the management of patients with HFpEF. The purpose of this review is to describe current and future applications of biomarkers in the management of patients with HFpEF.

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.

Resistance of guinea pig cardiac cytochrome c oxidase (complex IV) to extended ischemic time during global ischemia and reperfusion

Reactive oxygen species (ROS) produced from cardiac mitochondria during ischemia and reperfusion (IR) injury can damage respiratory complexes I–V. We reported that complexes I and III, but not IV, were damaged after 30 min global ischemia. Here we examined for damaging effects of extended ischemic time on complex IV. Guinea pig heart mitochondria were isolated after 30 min reperfusion in four groups: time control (TC), 35 min ischemia alone, 45 min ischemia alone, and 45 min ischemia plus a cocktail of ROS scavengers (MnTBAP, catalase, glutathione, resveratrol) given 10 min before ischemia and throughout reperfusion. Complex IV enzyme activity was assessed by the conversion of reduced cytochrome c to oxidized cytochrome c in a spectrophotometer at 550 nm. Phasic (systolic – diastolic) left ventricular pressures (LVP) were 92±1 (SEM), 47±7, 17±5, 23±3 mmHg, and diastolic LVPs were 0, 9±4, 41±5, 22±2 mmHg, for TC and ischemia lasting 35, 45, and 45 min + ROS scavengers, respectively. Despite differences in cardiac function, complex IV activity was not different among groups including TC. Respiratory complexes that are most susceptible to ischemic damage are important for developing targeted strategies to protect them. Understanding why and how complex IV is resistant to oxidative stress could provide insight into better strategies to protect the more susceptible complexes against IR injury. (supported by NIH HL89514)

Acute Administration of PPARγ Agonist Rosiglitazone in Isolated Hearts Differentially Aggravates Cardiac Ischemia Reperfusion Injury in a Consomic Rat Model

The effect of peroxisome proliferator‐activated receptor‐gamma (PPARγ) agonist rosiglitazone (RGZ), a thiazolidinedione (TZL), on cardiac ischemia/reperfusion (IR) injury is controversial. We tested effects of RGZ on post‐IR function and infarction in a consomic rat model that exhibits genetically determined cardioprotection. 15 min after 2 × 5‐min boluses of 50 μM RGZ or vehicle (Con), isolated hearts from Brown Norway (BN), Dahl Salt Sensitive (SS), and consomic (SS‐6BN) rats underwent 30 min global I and 120 min R. Systolic and developed left‐ventricular pressure (LVP), contractility, and coronary flow at 120 min R were decreased while diastolic LVP and infarct size increased in all Con groups, more so in SS than in BN or SS‐6BN hearts. RGZ enhanced IR injury more in SS‐6BN than in SS or BN hearts. Concurrent fluorescent redox state measurements suggested incomplete washout of RGZ and mitochondrial uncoupling before IR. These data confirm prior reports of deleterious effects of TZL on cardiac IR injury that appear to vary by species, dose, timing and route of administration, model used and PPARγ‐independent actions. These results also suggest genetic predisposition plays a role in the adverse response to TZLs. If translated clinically, PPARγ agonists may adversely enhance cardiac IR injury in genetically susceptible patients. Research supported by Department of Veterans Affairs (MR: CARA‐026–10F) and NIH.