Normal Left Ventricular End-diastolic Pressure Research Articles

Diagnosing heart failure with preserved ejection fraction in patients with unexplained dyspnoea using left ventricular pressure-volume loops at rest and on exertion

Abstract Background To date, diagnosing heart failure with preserved ejection fraction (HFpEF) remains challenging, especially in euvolaemic patients presenting with unexplained dyspnoea on exertion and reduced exercise capacity. A stepwise approach was introduced with the HFA-PEFF diagnostic algorithm*, in which a relevant number of patients has to undergo invasive workup for a final judgement. Purpose The present study aimed to examine a population of patients with unexplained dyspnoea on exertion, using the diagnostic methods endorsed by the HFA-PEFF algorithm as well as left ventricular (LV) pressure-volume loops at rest, on exertion, and during caval occlusion, in order to identify and describe different phenotypes of HFpEF. Methods We prospectively included patients with unexplained dyspnoea on exertion, a left ventricular ejection fraction (LVEF) of ≥ 50%, and without an obvious cause of the dyspnoea. All patients underwent a comprehensive invasive haemodynamic workup. After invasive rule-out of a haemodynamically relevant coronary artery stenosis, we performed a right heart catheterization at rest (R) and on exertion (E) with an arm ergometer. Real-time continuous pressure-volume loops were obtained using a 7-French conductance catheter at rest, on exertion, and under temporal preload reduction via partial occlusion of the vena cava inferior. Results Thirty patients were included. Two patients had to be excluded from further analysis (one due to a technical failure of the conductance catheter and one with severe hypertension (systolic blood pressure > 200 mmHg) during the assessment). The 28 patients in this analysis had a mean age of 64.4±9.7 years and 57% were female. Eleven patients fulfilled invasively easily obtainable diagnostic criteria of HFpEF (mean pulmonary capillary wedge pressure (mPCWP) at rest ≥ 15 mmHg, exertional mPCWP ≥ 25 mmHg, LV end-diastolic pressure (LVEDP) at rest ≥ 16 mmHg, or exertional LVEDP ≥ 25 mmHg) according to the current guideline*. An additional 15 patients had a normal mPCWP and LVEDP, but fulfilled diagnostic criteria for HFpEF measured by the conductance catheter (time constant of LV relaxation tau > 48 ms and/ or chamber stiffness b > 0.27). We referred to this group as "early HFpEF". Patients with early HFpEF had a significantly higher systolic blood pressure, a worse LV relaxation time, and were more likely to exhibit chronotropic insufficiency compared to the HFpEF group (Table 1). HFpEF patients were characterised by significantly higher natriuretic peptides, LVEDP on exertion, and LV stiffness compared to patients with early HFpEF (pressure-volume loops are depicted in Figure 1). Conclusion Invasive haemodynamic testing for HFpEF in patients with unexplained dyspnoea on exertion via right heart catheterization without obtaining LV pressure-volume loops had a false negative rate of 58%. Better detection, the prognosis, and treatment of this "early HFpEF" population warrants further research.Table 1Figure 1

Predictive value of protein-bound uremic toxins for heart failure in patients with chronic kidney disease.

This retrospective cohort study aimed to be the first to evaluate the association between plasma protein-bound uremic toxins (PBUTs) concentrations, echocardiographic parameters of heart failure (HF), and incident HF events in patients with chronic kidney disease (CKD) not on dialysis. Retrospective, single-centre, cohort study at the Ghent University Hospital, Belgium. Adults with CKD stages G1-G5, not on dialysis, could be included. Exclusion criteria were ongoing pregnancy, age <18years, active acute infection, active malignancy, history of transplantation, or a cardiovascular event within 3months prior to inclusion. Free and total concentrations of five PBUTs were quantified at baseline: indoxyl sulfate (IxS), p-cresyl sulfate (pCS), p-cresyl glucuronide (pCG), indole-3 acetic acid (IAA), and hippuric acid (HA). Patients were grouped into three echocardiographic categories: normal left ventricular ejection fraction (LVEF) and normal left ventricular end-diastolic pressure (LVEDP), normal LVEF and increased LVEDP, and reduced LVEF, based on available echocardiographic data in a time interval of ±6months around the plasma sample collection. A total of 523 patients were included between January 2011 and January 2014. Echocardiographic data within the predefined timeframe were available for 210 patients (40% of patients). Levels of pCG and pCS were significantly higher in patients with reduced (<50%) versus normal LVEF (P<0.05). After a median follow-up 5.5years, 43 (8.4%) patients reached the composite endpoint of hospitalization or mortality due to HF. Free fractions of IxS, pCS, and pCG showed the strongest association with clinical outcome: free IxS: HR 1.71 (95% CI 1.11-2.63; P=0.015), free pCS: HR 1.82 (95% CI 1.11-3.01; P=0.019), and free pCG: HR 1.67 (95% CI 1.08-2.58; P=0.020), and these results were independent of age, gender, body mass index, diabetes, and systolic blood pressure. In models that were also adjusted for serum creatinine, the free fractions of these PBUTs remained significant. Elevated free concentrations of IxS, pCG, and pCS were independently associated with an increased risk of HF events in non-dialysed CKD patients. Further research is necessary to confirm these findings and investigate the potential impact of PBUT-lowering interventions on HF events in this patient group.

Impact of left ventricular end-diastolic pressure as a marker for diastolic dysfunction on long-term outcomes in patients undergoing transcatheter aortic valve replacement

ObjectiveThe aim of this study was to investigate the proportion of elevated left ventricular end-diastolic pressure (LVEDP) as an indicator of diastolic function after transcatheter aortic valve replacement (TAVR) and its implication in predicting long-term mortality. MethodsWe analyzed retrospectively collected data on 3328 patients with severe aortic stenosis undergoing TAVR in our institution between July 2009 and June 2021. Patients were stratified into two groups based on invasive post-procedural LVEDP measurements: normal (<15 mmHg) vs. elevated (≥15 mmHg) LVEDP. ResultsMean age of the patients was 81.6 years, and 53.3% were female. Elevated post-procedural LVEDP was identified in 2408 (72.3%) patients. The 5-year mortality rates were higher in the group with elevated LVEDP compared with the group with normal LVEDP (27.4% vs. 8.3%, p = 0.01; hazard ratio [HR] 1.22, 95% CI 1.05-1.41). A multivariate model revealed the following independent predictors of mortality after TAVR: post-procedural elevated LVEDP (HR 1.24, 95% CI 1.01-1.53), pre-procedural significant tricuspid regurgitation (HR 1.24, 95% CI 1.02-1.52) and pulmonary hypertension (PH) (HR 1.53, 95% CI 1.26-1.86). In the present study, a significant paravalvular leak after TAVR was not associated with higher mortality (HR 1.45, 95% CI-0.95-2.19, p = 0.75). ConclusionElevated post-procedural LVEDP in patients who undergo TAVR is an independent predictor of all-cause mortality. Furthermore, PH and tricuspid regurgitation were also identified as predictors of mortality. These data confirm that diastolic dysfunction is an important predictor of mortality in TAVR and should be considered to guide procedure timing, favoring an early interventional approach and management in aortic stenosis patients.

Standard volume infusion unmasked diastolic dysfunction in pediatric heart transplant recipients during surveillance cardiac catheterization, but without echocardiographic correlates.

Adult experience evaluating left ventricular diastolic function (LVDFx) includes volume administration during catheterization while obtaining pulmonary capillary wedge pressures (PCWP) or left ventricular end diastolic pressures (LVEDP). Catheterization is inherently challenging in pediatric patients, making echocardiographic assessment ideal. Pediatric echocardiographic studies predicting LVDFx have variable hemodynamic and hydration conditions and have produced inconsistent results. We evaluated the association between simultaneous echocardiographic and catheterization assessment of LVDFx, using a fluid bolus for optimal loading conditions. Prospective cohort study of pediatric heart transplant recipients receiving echocardiogram simultaneous with routine cardiac catheterization. Mitral valve inflow velocities, septal and lateral wall tissue Doppler indices, and PCWP and/or LVEDP were obtained and repeated following a 10ml/kg bolus. Echocardiographic parameters were evaluated for an association with changes in PCWP or LVEDP following the bolus. Abnormal LVDFx was defined as PCWP or LVEDP ≥12 mm Hg. Twenty-nine patients underwent catheterization. Median pre-bolus PCWP and LVEDP were 11.0 mm Hg and 10.0 mm Hg, respectively. After bolus, median PCWP and LVEDP increased to 14.0 mm Hg (p< .001) and 13 mm Hg (p< .001), respectively. Of 21 patients with normal pre-bolus catheterization hemodynamics, 14 (66.7%) increased to abnormal following fluid bolus. Using area under an ROC, no echocardiographic parameter of LVDFx, or their ratios, were associated with predetermined abnormal LVEDP and/or PCWP. After bolus, our cohort demonstrated significant increases in LVEDP and/or PCWP, unmasking diastolic dysfunction. Fluid challenges should be considered in pediatric patients undergoing cardiac catheterization with suspected diastolic dysfunction. Echocardiographic measurements were unable to discriminate between normal and abnormal LVEDP and/or PCWP.

The novel left atrial strain parameters in diagnosing of heart failure with preserved ejection fraction

ObjectivesWe sought to evaluate the ability of the novel LA strain parameters to discriminate patients with heart failure with preserved ejection fraction (HFpEF) from individuals with risk factors of HFpEF.Methods and resultsA total of n = 389 patients with risk factors for HFpEF finally was prospectively enrolled into the study, 66 of them were diagnosed with HFpEF by the 2021 ESC HF guidelines. Fifty‐five patients were undergone left ventricular catheterization and simultaneous transthoracic echocardiography was performed, 35 of them with elevated left ventricular end‐diastolic pressure (LVEDP). Left atrial reservoir strain (LASr) was measured in all patients. LA filling index was defined as the ratio of mitral E and LASr and LA stiffness index was calculated as E/e′/LASr. Compared with the patients in the normal LVEDP subgroup, those in the elevated LVEDP subgroup showed significantly higher LA filling index, LA stiffness index, and LAVI/LASr. The receiver‐operating characteristic curve (ROC) analysis showed LASr (area under curve [AUC] .840), LA filling index (AUC .843), LA stiffness index (AUC .766), and LAVI/LASr (AUC .755) had good diagnostic accuracy for elevated LVEDP. Inter‐technique agreement analysis showed the novel algorithms with LA strain parameters had good agreement with the invasive LVEDP measurement, better than the 2016 ASE/SCAI algorithms (kappa .711 vs. .101). Furthermore, compared with patients without HFpEF, LASr was lower in HFpEF, LA filling index, LA stiffness index, and LAVI/LASr was higher in patients with HFpEF. ROC analysis showed the novel LA strain parameters with good accuracy (AUC .756 to .821) non‐inferior to conventional echocardiographic parameters could identify HFpEF, and LA stiffness index (AUC .821) was the best one.ConclusionThe novel LA strain parameters could be of potential usefulness in estimating LVEDP and incorporated into the 2016 EACVI/ASE criteria would improve the diagnostic efficiency. The novel LA strain parameters with good accuracy non‐inferior to conventional echocardiographic parameters could discriminate HFpEF from patients with risk factors of HFpEF.

Correlation of left atrial strain with left ventricular end-diastolic pressure in patients with coronary artery disease and preserved left ventricular ejection faction

Abstract Funding Acknowledgements Type of funding sources: None. Background Elevated left ventricular (LV) filling pressures are the main physiologic consequence of LV diastolic dysfunction. Left atrial (LA) strain was recently found useful to predict elevated LV filling pressures noninvasively. However, there are few reports on the role of LA strain when predicting LV filling pressure in patients with coronary artery disease (CAD). The aim of this study was to explore the correlation between LA strain and LV end-diastolic pressure (LVEDP) in patients with CAD and preserved LV ejection fraction. Methods Fifty-four patients with stable CAD were enrolled. Global atrial longitudinal strain was measured by averaging all atrial segments. Resorvoir (S-LAs), conduit (S-LAe), and contractile (S-LAa) phase strain were obtained. LVEDP was invasively obtained by left heart catheterization. Results Patients were divided into two groups: elevated LVEDP group (LVEDP &amp;gt; 15mmHg group: n = 23) and normal LVEDP group (LVEDP ≤ 15mmHg group: n = 31). Elevated LVEDP group showed significantly decreased S-LAs and S-LAa (S-LAs: 21.3 ± 7.2% vs. 27.5 ± 7.8%, p &amp;lt; 0.005; S-LAa: 9.7 ± 3.3% vs. 14.6 ± 3.4%, p &amp;lt; 0.0001). However, E/Ea and S-LAe were not significantly different between the two groups. LVEDP significantly correlated with S-LAa (r=-0.596, p &amp;lt; 0.0001) and S-LAs (r=-0.431, p &amp;lt; 0.001). Receiver operating characteristics curve analysis showed that S-LAa could predict elevated LVEDP (AUC = 0.84) and a cut-off value of S-LAa &amp;lt; 11.6% was able to most accurately identify patients with elevated LVEDP. Conclusions LA strain, especially S-LAa, provided additional diagnostic value for the noninvasive assessment of LV filling pressure in CAD patients with preserved LV ejection fraction.

Long-term Implications of Post-Procedural Left Ventricular End-Diastolic Pressure in Patients Undergoing Transcatheter Aortic Valve Implantation

Current risk models have only limited accuracy in predicting transcatheter aortic valve Implantation (TAVI) outcomes and there is a paucity of clinical variables to guide patient management after the procedure. The prognostic impact of elevated left ventricular end-diastolic pressure (LVEDP) in TAVI patients is unknown. The aim of the present study was to evaluate the prognostic value of after-procedural LVEDP in patients who undewent TAVI. Consecutive patients with severe symptomatic aortic stenosis who undewent TAVI were divided into 2 groups according to after-procedural LVEDP above and below or equal 12 mm Hg. Collected data included baseline clinical, laboratory and echocardiographic variables. We evaluated the impact of elevated vs. normal LVEDP on in-hospital outcomes, short- and long-term mortality. Eight hundred forty-five patients were included in the study with complete in-hospital and late mortality data available for all survivors (median follow-up 29.5 months [IQR 16.5 to 48.0]). The mean age (±SD) was 82.3±6.2 years and mean Society of Thoracic Surgery score was 4.0%±3.0%. Patients with LVEDP>12 mm Hg (n = 591, 70%) and LVEDP≤12 mm Hg (n = 254, 30%) had a 6-months mortality rate of 6.8% and 2%, respectively (P=0.004) and a 1-year mortality rate of 10.1% vs 4.9%, respectively (p = 0.017). By multivariable analysis, after-procedural LVEDP>12 mm Hg was independently associated with all-cause mortality (HR 2.45, 95% CI 1.58 to 3.76, p <0.001) during long-term follow-up. In conclusion, elevated after-procedural LVEDP in patients who undewent TAVI is an independent predictor of mortality following TAVI. Further research regarding the use of LVEDP as a tool for after-procedural medical management is warranted.

STIFF LEFT ATRIAL SYNDROME: THE MYSTERY BEHIND A PRESUMPTIC DIAGNOSIS OF PULMONARY ARTERY HYPERTENSION

SESSION TITLE: Global Case Report Posters SESSION TYPE: Global Case Reports PRESENTED ON: October 18-21, 2020 INTRODUCTION: Atrial Fibrillation (AF) is one of the most prevalent arrhythmia. Radio frequency catheter ablation (RFCA) is an effective treatment for AF and is superior to medical therapy. here we report a case of he stiff left atrium syndrome (SLAS) is a newly recognized post-procedure complication of RFCA due to left atrial (LA) scarring and fibrosis. CASE PRESENTATION: A 66 y/o female with a history of AF status post four RFCAs, suspected heart failure with preserved ejection fraction (HFpEF) with associated PH presented to the emergency room with shortness of breath. An echo cardiogram showed normal left ventricular (LV) systolic function and dilation of the Left atrium. Right heart catheterization (RHC) showed a pulmonary capillary wedge pressure (PCWP) of 32mmHg, a mean pulmonary artery pressure (PAP) of 62mmHg, and near normal peripheral vascular resistance indicating PVH. Due to refractory symptoms a follow up left and RHC showed similar MPAP and PCWP but left ventricular end diastolic pressure (LVEDP) was surprisingly normal at 12mmHg. A CT scan showed normal pulmonary veins without stenosis. Given the discrepancy of elevated LA pressure with a normal LVEDP, a diagnosis of SLAS was confirmed. Treatment with diuretics and control of risk factors were initiated. DISCUSSION: The differential diagnosis for a patient presenting with dyspnea and pulmonary hypertension with a history of prior RFCA includes HfpEF, pulmonary vein stenosis, valvular pathology, and SLAS, with HFpEF begin the most common . The estimated incidence of SLAS after RFCA is 1.4% - 8%. Key distinguishing features of SLAS include prominent V-waves on LA pressure tracings (via PCWP) disproportionate to the LVEDP. The diagnosis of SLAS is challenging and can be easily missed. For example, isolated post-capillary PH with a normal LV ejection fraction would suggest a diagnosis of HFpEF. However, a LHC in a patient with a stiff left atrium that demonstrated a significantly elevated LA V-wave and a surprisingly normal LVEDP would indicate no LVDD. Thus, in addition to imaging with echocardiography, invasive hemodynamic testing with simultaneous LHC to measure the LVEDP in addition to RHC for the PAP and PCWP is essential to make the difficult diagnosis of SLAS. Diuretics are currently considered mainstay treatment for SLAS. Recent studies have evaluated the novel use of an interatrial septal device to create an atrial septostomy which relieves LA pressure by creating a left-to-right shunt. In a trial for patients with HFpEF, an atrial septostomy led to a significant decrease in PCWP (28%), symptomatic improvement, a longer 6-minute walk distance, and better quality of life after 30 days. CONCLUSIONS: This case demonstrates the diagnostic challenge of SLAS and the importance of invasive hemodynamic testing with simultaneous RHC and LHC in addition to imaging to identify the true underlying cause of pulmonary hypertension. Reference #1: Gibson, D.N., et al., Stiff left atrial syndrome after catheter ablation for atrial fibrillation: clinical characterization, prevalence, and predictors. Heart Rhythm, 2011. 8(9): p. 1364-71. Reference #2: Maeder, M.T., et al., Pulmonary hypertension in stiff left atrial syndrome: pathogenesis and treatment in one. ESC heart failure, 2018. 5(1): p. 189-192. Reference #3: Chandrashekar, P., et al., Atrial Septostomy to Treat Stiff Left Atrium Syndrome. Circulation. Heart failure, 2017. 10(7): p. e004160. DISCLOSURES: No relevant relationships by Mark Cromer, source=Web Response No relevant relationships by Abhijit Raval, source=Web Response

P4474The role of nr4a1 in angiotensin-ii model of pressure overload induced cardiac remodelling

Abstract Introduction Adverse cardiac remodelling is a response of the heart to various stimuli and if left untreated can progress to heart failure. Nr4a1, an orphan nuclear receptor, has been shown to have conflicting contributions to adverse cardiac remodelling in several aetiologies, making its role in cardiac remodelling unclear. Purpose To investigate the contribution of Nr4a1 to adverse remodelling in a model that does not cause a pressor response, in order to gain a clearer understanding of the actions of Nr4a1 in the absence of alterations in hemodynamic load. Methods 8 week old Nr4a1−/− mice received an IP infusion of Ang-II via osmotic pump (1500ng/kg) for 3 or 7 days. IP administration does not cause increased blood pressure. Age-matched wild type (WT) C57B/6 mice served as controls. Left ventricular (LV) structure and function was assessed by echocardiography and pressure catheter. LV tissue was collected for molecular and histological analyses. Results Echocardiography identified a trend towards a thickening of the LV anterior wall in the Nr4a1−/−+Ang-II 7 days group, which was also reflected in the increase in LV/tibia ratio (Nr4a1−/−+Ang-II 5.7±0.67 mg/mm vs WT+Ang-II 4.64±0.5 mg/mm, p&lt;0.0003; Nr4a1−/−+Ang-II 5.7±0.67 mg/mm vs Nr4a1−/−+Saline 4.7±0.6 mg/mm, p&lt;0.0008). No hypertrophy was observed in the WT+Ang-II 7 days group reflective of no haemodynamic load. Our results also showed that cardiac fibrosis was decreased in Nr4a1−/−+Ang-II mice following 7 days of Ang-II. LV end diastolic pressure was elevated in WT+Ang-II mice compared to WT+Saline mice (5.8±6.0 mmHg vs 1.2±2.0 mmHg, p&lt;0.05), but normalised in Nr4a1−/−+Ang-II (2.4±2.9 mmHg) reflective of the reduced fibrosis in the Nr4a1−/−+Ang-II mice. Inflammation is an underlying cause of fibrosis. There was a significant increase in macrophages at 3 days in both WT+Ang-II (46.38±44.14 cells/LV section vs WT+Saline: 5.4±3.82 cells/LV section)and Nr4a1−/−+Ang-II mice (224.4±44.83 cells/LV section vs Nr4a1−/−+Saline: 8.04±10.59 cells/LV section). Nr4a1−/−+Ang-II also had increased macrophages compared to WT+Ang-II group (p&lt;0.0001). The increase in macrophages does not appear to be due to recruitment since the chemokine CCL2 was not increased in Nr4a1−/− mice with Ang-II. In addition, despite the dramatic increase in inflammatory cell number in the Nr4a−/−+Ang-II mice, there does not appear to be an increased active inflammatory response since LV IL-6 levels were not increased in this group. LV end diastolic pressure Conclusion Nr4a1 plays a role in regulating cardiac remodelling with its absence making the heart more prone to cardiac hypertrophy in response to stimulation, even in the absence of hemodynamic load. Interestingly though, this hypertrophic response occurs with reduced fibrosis and normal LV end diastolic pressure, which together would seem to indicate adaptive hypertrophy as opposed to pathological hypertrophy in the absence of Nr4a1. Acknowledgement/Funding George and Mary Thompson Fellowship

Maladaptive left ventricular remodeling in women: An analysis from the Women's Ischemia Syndrome Evaluation–Coronary Vascular Dysfunction study

BackgroundWomen represent approximately half of heart failure hospitalizations and are disproportionately affected by heart failure with preserved ejection fraction (HFpEF). Women with signs and symptoms of ischemia, preserved left ventricular ejection fraction (LVEF), and no obstructive coronary artery disease (CAD) often have elevated left ventricular end-diastolic pressure (LVEDP). However, isolated elevated LVEDP in the absence of coronary microvascular dysfunction (CMD) is not understood. MethodsAmong 244 women with signs and symptoms of ischemia, no obstructive CAD, and preserved LVEF who underwent invasive coronary reactivity testing (CRT), 43 (18%) women had no evidence of CMD. LVEDP was measured at time of CRT, and left ventricular (LV) volumes and mass were assessed by cardiac magnetic resonance (CMR) imaging. ResultsOf the 43 women without CMD, 24 (56%) had elevated LVEDP [mean 18 mm Hg (SD = 3)] compared to 19 (44%) with normal LVEDP [11 mm Hg (SD = 3)]. The elevated LVEDP group had a comparatively higher systolic and diastolic blood pressure, lower LV end-diastolic volume index (EDVI), and higher mass-to-volume ratio. Other functional parameters were not significantly different. ConclusionsAmong women with signs and symptoms of ischemia without obstructive CAD, absence of CMD, and preserved LVEF, isolated elevated LVEDP is associated with a significantly higher systolic and diastolic blood pressure, higher LV mass-to-volume ratio and lower LV EDVI. These results suggest these women have maladaptive remodeling to blood pressure. Given the relatively high prevalence of HFpEF in women, these hypothesis-generating results suggest that further study of ventricular remodeling is warranted.

Grade I diastolic dysfunction and elevated left ventricular end-diastolic pressure: Mitral Doppler inflow, pulmonary veinatrial reversal, and the M-mode mitral B-bump.

Grade I diastolic dysfunction (DD) is generally associated with a normal mean left atrial pressure (LAP) and normal left ventricular end-diastolic pressure (LVEDP). The first hemodynamic alteration seen in DD, however, is the development of an elevated LVEDP with a persistent normal LAP. This is manifested by echocardiography as a continued mitral pulsed wave (PW) E/A <0.8 (Grade I DD), but with evidence of an elevated LVEDP. Such findings include alterations in PV flow, mitral PW inflow response to Valsalva maneuver, and also the presence of a B-bump on the mitral M-mode tracing. When assessing diastolic function, it may be clinically helpful to assess for this early hemodynamic manifestation of DD.

Effects of fasudil on isoproterenol induced cardiac hypertrophy in rats

To investigate the effects and mechanisms of fasudil (Fas) on cardiac hypertrophy (CH) induced by isoprenaline(Iso) in rats. Except for the normal control group, the rest three groups rats were injected subcutaneously with Iso(5mg/kg) for setting up CH model. SD rats were randomly divided into four groups:Normal control group, Iso model group, Fas with low-dose group (5 mg/kg, i.p) and Fas with high-dose group (20 mg/kg, i.p). Animals were treated with Fas for 8 weeks. After the treatment, the following index were detected:heart rate (HR), left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), left ventricular systolic maximum rate (+dp/dtmax) and left ventricular diastolic maximum rate (-dp/dtmax). The body weight(BW) and heart weight (HW) were weighed and heart weight index (HWI) was calculateed. Myocardial tissue specimens, HE and Masson staining were performed for observing the histopathological changes. The protein expression of extracellular signal-regulated kinase 1/2 (ERK1/2) in myocardial tissue was determined by using immunohistochemical methods. The expression of ERK1/2 mRNA in the myocardial tissue was detected by using semi-quantitative RT-PCR method. Compared with normal control group, HR and LVEDP wereincreased significantly, while LVSP and ±dp/dtmax were decreased significantly; HWI was increased significantly in CH group; The myocardial cell volume and the cell gap were increased,cells arranged disorder, and severe myocardial interstitial fibrosis was presented in CH group. The expression of ERK1/2 mRNA was significantly increased. After Fas treatment, the systolic and diastolic functions of heart were improved, cell volume was reduced, cell gap became small, cells arranged in neat rows, and the fibrosis was significantly reduced. The expressions of RhoA, ERK1/2 mRNA were significantly reduced. The damages of myocardial tissue were improved in different degrees. ERK1/2 signaling pathway is involved in Iso induced CH. Fas protects against the CH of rats induced by Iso, which mechanisms may be related with blocking ERK1/2 signaling pathway.

Evaluate the sensitivity and specificity echocardiography in trans-Doppler and tissue Doppler method in the estimation of left ventricular end-diastolic pressure.

Background:Non-invasive survey of left ventricular end-diastolic pressure (LVEDP) by transmitral Doppler echocardiography and tissue Doppler imaging carries important information about left ventricular diastolic function in chosen subsets of patients. This study is planned to assess whether mitral annular velocities (lateral annulus) as assessed by tissue Doppler imaging and transmitral Doppler echocardiography are associated with invasive measures of left ventricular end diastolic pressure and also the estimation of sensitivity and specificity of these methods.Methods:One hundred ten consecutive patients admitted to cardiac catheterization underwent simultaneous Doppler interrogation measurements of left ventricular pressure were obtained with fluid-filled pressure. The E/Ea ratio associated well with LVEDP (P<0.005 r=0.4) and the correlation more marked in the patients with reduced contractile function. This correlation was independent of gender.Results:The E/Ea ration of <8 best discriminated elevated (LVEDP>12) from normal LVEDP with a sensitivity of 73.5% and specificity 57.8%, PPV and NPV were 75.75% and 55% respectively. Our study results also showed that quantitative estimation of LVEDP could be suggested by the equation of LVEDP=1.2 E/Ea+6.67± 8 mmHg P<0.005 B=0.4.Male-LVEDP=0.9 E/Ea + 7.78±7.67 mmHg (r=0.4 Pa<0.005)EF>_50% -+LVEDP=1.48 E/Ea + 9.05±5.23 (r=0.4 P<0.05)EF<50% -+LVEDP=0.76 E/Ea + 8.4±2.3 (r=0.5 P<0.005)

Poor Agreement between Pulmonary Capillary Wedge Pressure and Left Ventricular End-Diastolic Pressure in a Veteran Population

BackgroundAccurate determination of left ventricular filling pressure is essential for differentiation of pre-capillary pulmonary hypertension (PH) from pulmonary venous hypertension (PVH). Previous data suggest only a poor correlation between left ventricular end-diastolic pressure (LVEDP) and its commonly used surrogate, the pulmonary capillary wedge pressure (PCWP). However, no data exist on the diagnostic accuracy of PCWP in veterans. Furthermore, the effects of age and comorbidities on the PCWP-LVEDP relationship remain unknown.MethodsWe investigated the PCWP-LVEDP relationship in 101 patients undergoing simultaneous right and left heart catherization at a large VA hospital. PCWP performance was evaluated using correlation and Bland-Altman analyses. Area under Receiver Operating Characteristics curves (AUROC) for PCWP were determined.ResultsPCWP-LVEDP correlation was moderate (r = 0.57). PCWP-LVEDP calibration was poor (Bland-Altman limits of agreement −17.2 to 11.4 mmHg; mean bias −2.87 mmHg). 59 patients (58.4%) had pulmonary hypertension; 15 (25.4%) of those met pre-capillary PH criteria based on PCWP. However, if LVEDP was used instead of PCWP, 7/15 patients (46.6%) met criteria for PVH rather than pre-capillary PH. When restricting analysis to patients with a mean pulmonary artery pressure of ≥25 mmHg and pulmonary vascular resistance of >3 Wood units (n = 22), 10 patients (45.4%) were classified as pre-capillary PH based on PCWP ≤15 mmHg. However, if LVEDP was used, 4/10 patients (40%) were reclassified as PVH. Among patients with any type of pulmonary hypertension, PCWP discriminated moderately between high and normal LVEDP (AUROC, 0.81; 95%CI 0.69–0.94). PCWP-LVEDP correlation was particularly poor in patients with COPD or obesity.ConclusionReliance on PCWP rather than LVEDP results in misclassification of veterans as having pre-capillary PH rather than PVH in almost 50% of cases. This is clinically relevant, as misclassification may lead to inappropriate therapies and adverse events.

Association of increased extracellular volume expansion with elevated left ventricular end diastolic pressure in patients with nonischemic cardiomyopathy

Background Myocardial extracellular volume expansion is a marker of myocardial fibrosis which is associated with myocardial stiffness and impaired relaxation property. In this study we investigated the association of extracellular volume indices using T1 mapping and left ventricular end diastolic pressure (LVEDP) using left atrial transit time in patients with nonischemic cardiomyopathy. Methods All subjects were prospectively recruited to undergo cardiac MRI in a 1.5 T scanner. Modified Look-Locker Inversion recovery sequence was used with motion correction included in the post processing algorithm. Pre-contrast and post contrast (20 minutes after gadolinium injection at 0.15 mmol/kg) T1 maps of the blood pool and myocardium were assessed in basal, mid and apical segments of the short axis planes using Siemens software. Calculated T1 indices were the average value of the basal and mid slice which included the pre- and post-contrast myocardial T1, contrast partition coefficient using the ratio of signal change in blood and myocardium before and after contrast administration, and extracellular volume fraction (ECV) which was partition coefficient multiplied with one minus hematocrit to account for the blood contrast volume of distribution. LVEDP was assessed using normalized mean left atrial transit time derived from the time-signal intensity curve of the first pass perfusion image during gadolinium injection at 0.01 mmol/kg. Results Compared to the normal controls (N = 8) patients with nonischemic cardiomyopathy (N = 31) had lower LV ejection fraction (EF) (47 ± 12% vs 54 ± 3%, p = 0.021) and higher LVEDP (14 ± 5 mmHg vs 10 ± 2 mmHg, p = 0.014). Using Pearson’s correlation increased partition coefficient, ECV and pre-contrast myocardial T1 were significantly correlated with elevated LVEDP: r = 0.385 (p = 0.021), r = 0.355 (p = 0.029) and r = 0.335 (p = 0.04), respectively. In dichotomized analysis elevated LVEDP (≥13 mmHg, N = 13) was associated with significantly higher partition coefficient (0.51 ± 0.1 vs 0.45 ± 0.06, p = 0.004), higher ECV (0.30 ± 0.06 vs 0.26 ± 0.03, p = 0.002) and higher pre-contrast myocardial T1 (1040 ± 123 ms vs 983 ± 44 ms, p = 0.045) when compared to those with normal LVEDP ( < 13 mmHg, N = 26). Among patients with elevated LVEDP (average 19 ± 3 mmHg) there were no significant differences in partition coefficient, ECV and pre-contrast myocardial T1 between those with preserved or reduced LVEF. In contrast, there was a lack of significant association between post-contrast myocardial T1 and LVEDP. Conclusions Increased contrast partition coefficient, ECV and precontrast myocardial T1 were significantly associated with elevated LVEDP in patients with nonischemic cardiomyopathy thereby supporting the link between extracellular volume expansion and myocardial diastolic dysfunction. Quantitative tissue characterization combined with hemodynamic assessment underscores the value of cardiac MRI in the evaluation of nonischemic cardiomyopathy.

Left Ventricular Diastolic Dysfunction in Patients With Mitral Stenosis Undergoing Percutaneous Mitral Balloon Valvotomy

ObjectiveTo investigate the effect of left ventricular diastolic dysfunction on outcome in patients with mitral stenosis undergoing percutaneous mitral balloon valvotomy (PMBV). Patients and MethodsWe evaluated consecutive patients with mitral stenosis who underwent PMBV from November 1, 2002, through October 30, 2011, at our institution. ResultsOf 107 total patients, 35 (32.7%) had diastolic dysfunction, defined as a preprocedural elevation in left ventricular end-diastolic pressure (LVEDP) (>15 mm Hg). The LVEDP was normal in the remaining 72 patients (≤15 mm Hg). Clinical factors associated with diastolic dysfunction were body mass index (32±7 vs 28±5; P=.004) and diabetes mellitus (29% vs 6%; P=.002), but no differences were found in severity of pulmonary hypertension or degree of improvement in mitral valve hemodynamics after PMBV between the 2 groups. Survival free of recurrent severe symptoms, repeated PMBV, or mitral valve replacement was worse in patients with elevated LVEDP vs normal LVEDP (1-year estimate, 42% vs 81%; hazard ratio, 2.83; 95% CI, 1.62-4.96). ConclusionIn patients referred for treatment of symptomatic mitral stenosis, left ventricular diastolic dysfunction may contribute to elevated left atrial pressure, and its presence is associated with a greater risk of failure of PMBV to improve symptoms. These data have implications for counseling and patient selection for PMBV.

Elevated left ventricular end-diastolic pressure favours closure of foramen ovale

Objective It has been described that prevalence of patent foramen ovale (PFO) declines with age. Our hypothesis was that persistent high pressures in the left atria (LA), may facilitate closure of PFO and age would not play a role.Methods and results The prevalence of PFO was studied in 201 consecutive patients with suspicion of cardioembolic stroke by contrast transoesophageal echocardiography. Left ventricular end-diastolic pressures (LVEDP) were estimated non-invasively by transthoracic echocardiography. Patients with normal diastolic function (DF) or with diastolic dysfunction (DD) stage I were considered as having normal LVEDP whereas patients with DD stage II or III as having elevated LVEDP. Prevalence of PFO was 42.8% and it was smaller in patients with elevated LVEDP than in patients with normal LVEDP (21.2% vs. 51.7%, P< 0.01). There was a smaller prevalence of PFO in patients with DD stage II than in patients with DD stage I or normal DF (25% vs. 51 and 54%, both P< 0.05). Size of the LA was larger in patients without PFO [34.73 ml/m² (24.14–40.84ml/m²) vs. 27.86 ml/m² (21.37–34.68 ml/m²), P< 0.05]. Mean age was 64.2 years (57.38–75.77) with no diff erence between patients with PFO and without PFO. In multivariate analysis Eustachian valve, atrial septal aneurysm, elevated LVEDP and large LA remained signifi cantly associated (P < 0.05) with PFO.Conclusion Elevated LVEDP and enlargement of LA are negatively associated with PFO. The higher the LVEDP, the lower the prevalence of PFO. Age is not associated with PFO.

Value of conventional and tissue Doppler echocardiography in the estimation of left ventricular filling pressure

Various conventional and tissue Doppler parameters have been proposed for the estimation of left ventricular filling pressure. To assess the utility of several conventional and tissue Doppler parameters in the estimation of left ventricular end diastolic pressure (LVEDP). Among 40 consecutive patients LVEDP was correlated with pulsed Doppler of mitral inflow and pulsed tissue Doppler of lateral mitral annulus. Among all studied Doppler variables, E ′/ A ′ ratio showed the most significant correlation with LVEDP ( r = 0.612, p < 0.001). Among patients with grade II and III diastolic dysfunction, E ′/ A ′ ratio showed the best correlation with LVEDP ( r = 0.81, p < 0.001) with the following regression equation: LVEDP = 1.77 + (20.4 × E ′/ A ′) while in patients with grade I diastolic dysfunction no correlation exists ( r = 0.11, p = 0.63). Weak significant correlation was detected between E / E ′ ratio and LVEDP ( r = 0.382, p = 0.016). An E / E ′ ratio > 12 had 25% sensitivity and 100% specificity to identify patients with elevated LVEDP (>15 mm Hg) with a positive predictive value of 100%. On the other hand, an E/ E ′ ratio of <8 had 77% sensitivity and 57% specificity to identify patients with normal LVEDP with a negative predictive value of 31%. Of all echocardiographic variables investigated, E ′/ A ′ ratio was identified as the best index to estimate LVEDP especially in patients with advanced LV diastolic dysfunction; a relation that was not found for other conventional or tissue Doppler variables including the E / E ′ ratio.

Association of global and regional central circulation transit time with left ventricular end diastolic pressure using dynamic magnetic resonance imaging

Background Prolonged central circulation transit time (TT) has long been associated with heart failure and left ventricular (LV) dysfunction. However, it is not known which portion of the central circulation is associated with this prolongation. Moreover, the relation of global and regional TT to LV end diastolic pressure (LVEDP) is not defined. In this study we assessed the global and regional TT in each portion of the central circulation and investigated their relations to LVEDP in patients undergoing cardiac catheterization. Methods All patients were prospectively recruited and underwent cardiac MRI within 5 hours of cardiac catheterization. Dynamic MR images were acquired during the infusion of gadopentetate dimeglumine (0.01 mmol/kg) at 6 ml/s. Areas of interest were drawn and propagated through phases in the right atrium (RA), right ventricle (RV), main pulmonary artery (PA), left and right lung, left atrium (LA), LV and ascending aorta to construct timeintensity curves. TT was defined as the time between the peaks of time-intensity curves. All TTs were normalized to RR intervals. Central circulation TT was defined as TT from RA to aorta, while regional TT was defined as RA to RV, RV to PA, PA to lungs (averaged value of the left and right lung), lungs to LA, LA to LV, and LV to aorta. LVEDP was assessed during cardiac catheterization. Results Of the 48 subjects studied the mean age was 59 years and 32 (67%) were male. Average LV ejection fraction (LVEF) was 48±15% and the LVEDP 15±8 mmHg. Central TT was significantly prolonged in patients with elevated LVEDP (>12 mmHg) 15.7±5.8 cardiac cycles vs. 10.5±2.2 cardiac cycles (p=0.002) in those with normal LVEDP (≤12 mmHg). Regional analysis demonstrated that TT prolongation was present in PA to lungs, lungs to LA, LA to LV and LV to aorta but not in RA to RV and RV to PA. The multivariate regression model which included all regional TTs as covariables showed that TT from lung to LA had the strongest association with LVEDP (beta coefficients 0,424, p<0.001) followed by TT from LA to LV (0,325, p=0.007) and TT from PA to lungs (0,240, p=0.037). TTs from other regions were not significantly associated with LVEDP. Conclusions Central and regional circulation TT can be assessed by dynamic MR imaging. Central TT was significantly prolonged in patients with elevated LVEDP largely due to regional TT prolongation in lungs to LA, LA to LV and PA to lungs circulation. Funding None.

Is mitral E/E' ratio a reliable predictor of left ventricular diastolic pressures in patients without heart failure?

Aim Conflicting evidence exists as to whether the mitral E/E' ratio can be a reliable predictor of the left ventricular end-diastolic pressure (LVEDP). Our aim was to assess the value of the mitral E/E' ratio for the estimation of left ventricular diastolic pressures (LVDP) in patients without heart failure (HF). Echo-Doppler examination and left heart catheterization were carried out in 100 consecutive patients to assess the correlation between echo-Doppler parameters and the LVDP. The E/A ratio showed the best correlation with the pre-a LVDP and the LVEDP, whereas septal and mean E/E' ratios were significantly correlated with pre-a LVDP but not with the LVEDP. No difference in the echo-Doppler parameters was found between patients with normal and elevated LVEDP. Mitral E/E' ratio was significantly higher in patients with an ejection fraction (EF) <50% compared with those with the EF ≥ 50% and in patients with a dilated left ventricular (LV) compared with those with a normal LV. No significant difference in mean LVEDP was found among the three groups with E/E' ratios of <8, 8-15, and >15. The best cut-off values identified by receiver operating characteristic curve analysis for septal, lateral, and mean E/E' had sensitivities of 53, 68, and 54% and specificities of 66, 51, and 69% for identifying a >15 mmHg LVEDP. In patients without HF mitral E/E' ratio is influenced by EF and LV volumes and is better correlated with the pre-a LVDP than with the LVEDP. The suboptimal sensitivity and specificity of E/E' for predicting increased LVDP suggest that the mitral E/E' ratio is of limited clinical value in patients without HF.