Elevated LVEDP Research Articles

Abstract 16888: Reduced Diastolic Myocardial Strain From Interstitial Fibrosis Dissociates the Myocardial Transcriptional Response to Transient Increases in Left Ventricular End-Diastolic Filling Pressure (LVEDP)

Objective: Brief repetitive pressure overload (RPO) in swine leads to interstitial fibrosis and reduced diastolic left ventricular (LV) compliance in the absence of LV hypertrophy. The present study determined whether LV compliance influences the transcriptional response to elevated LVEDP. Methods: Brief pressure overload was produced with phenylephrine (1-2 hours) to elevate LVEDP from 11.4±1.2 mmHg to 30.3±2.4 mmHg in normal hearts (n=6) and from 12.3±0.9 mmHg to 30.0±1.6 mmHg after 2 weeks of daily RPO (n=8). Interstitial fibrosis was quantified using picrosirius red staining. Whole tissue RNA-seq was performed on RNA isolated from LV samples collected 24 hours after increased LVEDP in each group vs. unstressed controls (n=10). Transcripts were mapped to Ensembl Sscrofa 11.1 gene index, aligned with Salmon, and mapped to human homologs using Biomart. Differential expression analysis was performed with DESeq2 package and gene ontology was performed using DAVID. Genes were considered differentially expressed (DEG) if the absolute value of log2fc was > 0.477 (∼33% change) and a p < 0.05. Results: Chronic RPO increased interstitial fibrosis (12.9±1.8% vs. 6.5±1.5% in normals; p<0.05) and markedly reduced diastolic circumferential strain (1.5±2.7% vs. 20.3±4.4% in normals; p<0.05). Stretch activated genes ANP and BNP were significantly upregulated with increased LVEDP in normal hearts (fc 35.8 and 14.3; both p<9x10 – 9 ), but not in hearts after RPO (fc 1.4 and 1.8; both p-ns). Among the 15,133 total genes expressed, increased LVEDP induced 3,534 DEGs in normal hearts. Top gene ontology enriched pathways included ECM, cytoskeleton, cell junction, and microtubules. In contrast, there was a marked reduction in DEGs (117) observed when LVEDP was elevated in the stiff LV after RPO. Conclusions: Elevated LVEDP in the normal heart leads to many DEGs including the ECM and cytoskeleton proteins involved in reducing LV compliance. In contrast, after RPO and the development of interstitial fibrosis, there is a marked attenuation of the transcriptional response to increased LVEDP. These data support the notion that myocardial strain rather than pressure is the primary physiological determinant of the transcriptional response to pressure overload.

A tale of 2 conversions: Dichotomous decision in the spectrum of Shone syndrome is still a dilemma

A tale of 2 conversions: Dichotomous decision in the spectrum of Shone syndrome is still a dilemma

Clinical Memory of COVID-19 Pandemic: A Comparative Analysis of Clinical and Angiographic Characteristics of Patients with Acute Coronary Syndrome

Objectives: To describe the clinical characteristics and angiographic features of COVID-19 patients presenting with acute coronary syndrome (ACS) and to compare with non-COVID-19 ACS patients presenting simultaneously. Methodology: In a case control design, data were extracted from a prospectively collected COVID-19 and NCDR registry. All ACS patients who underwent cardiac catheterization from April 2020 to May 2021 were included. All of the patients were taken to the Cath lab for diagnostic coronary angiography and possible percutaneous intervention. Demographic and clinical characteristics, angiographic features, and in-hospital outcomes were compared between ACS patients with and without COVID-19. Results: A total of 4027 COVID-19 negative patients, and 80 COVID-19 positive were included. Total of 83% in COVID-19 and 88% in non-COVID-19 group had ST elevation myocardial infarction. Majority of the COVID-19 positive patients had sub-optimal TIMI flow grade (<III) post procedure and had a high thrombus burden (11.2% vs. 2.9%; p<0.001). Majority of the patients who had COVID-19 and ACS required mechanical circulatory support (48.8% vs. 0.3%; p<0.001). The mortality rates were also higher in COVID-19 positive group (38.8% vs. 1.3%; p<0.001). Among the COVID-19 positive patients 66.3% (53) had high thrombus burden (≥4 grade), intervention was performed in 73.7% (59). Post-intervention myocardial blush grade ≤2 was observed in 57.6% (34), slow flow in 85.3% (29), and phasic flow possibly due to elevated LVEDP in 41.2% (14) patients. Conclusion: COVID-19 patients with ACS had a higher severity of illness at presentation and worse outcomes as compared to simultaneously presenting non-COVID patients.

Abstract 12982: Between a Rock and a Hard Place: Stiff Left Atrial Syndrome in a Patient With Hereditary Rickets

Introduction: Stiff left atrial syndrome (SLAS) is an uncommon cause of pulmonary hypertension (PH) that has been described as a complication of ablation for atrial fibrillation; here we describe a unique case of SLAS in the setting of extensive left atrial calcification from the treatment of hereditary hypophosphatemia (HH). Case Presentation: A 44-year-old woman with a history of HH presented for evaluation of progressive exertional dyspnea. Previous treatment with calcitriol and phosphate had been complicated by severe calcific mitral and aortic stenosis requiring aortic and mitral valve replacement eight years prior. She reported initial improvement in her symptoms after surgery, but more recently had noted worsening dyspnea and edema despite escalating her home diuretic dose. TTE was notable for moderately severe PH with no evidence of valvular or ventricular dysfunction. Chest CT showed extensive left atrial mural calcification (Figure A) with corresponding calcium visible in the wall of the left atrium on TTE (Figure B). The patient was admitted and underwent IV diuresis followed by RHC confirming mPAP of 41mmHg with a PCWP of 20mmHg and prominent V waves to 33mmHg (Figure C-D). PCWP was confirmed by wedge oxyhemoglobin saturation. Symptoms were improved but not resolved with additional diuresis. Discussion: In this patient with metastatic calcinosis related to the treatment of her HH, we believe her PH is most likely secondary to SLAS due to marked circumferential left atrial calcification. SLAS is characterized by decreased left atrial compliance, leading to large V waves in the absence of mitral regurgitation or an elevated LVEDP. Beyond diuresis, there are no proven treatments for PH due to SLAS.

EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS WITHOUT ANY PERIPHERAL EOSINOPHILIA

EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS WITHOUT ANY PERIPHERAL EOSINOPHILIA

Anesthetic management of primary cardiac tumor in the coronary sinus and right atrium

The patient presented with complete atrioventricular block and dyspnea. They had a primary cardiac tumor originating in the coronary sinus, a rare site of origin. It filled the sinus and involved the right atrium. The patient might have presented with complete atrioventricular block due to tumor invasion and respiratory distress due to elevated LVEDP as the tumor filled the coronary sinus. As for anesthesia management, in addition to the usual management, we observed CS obstruction and also considered myocardial protection methods. It is important to anticipate the risks and develop an appropriate anesthetic plan accordingly.

Non-Invasive Estimation of Left Ventricular Filling Pressure Based on Left Atrial Area Strain Measured With Transthoracic 3-Dimensional Speckle Tracking Echocardiography in Patients With Coronary Artery Disease.

Background: Chronic elevation of left ventricular (LV) diastolic pressure (DP) or chronic elevation of left atrial (LA) pressure, which is required to maintain LV filling, may determine LA wall deformation. We investigated this issue using transthoracic 3-dimensional speckle tracking echocardiography (3D-STE).Methods and Results: We retrospectively enrolled 75 consecutive patients with sinus rhythm and suspected stable coronary artery disease who underwent diagnostic cardiac catheterization and 3D-STE on the same day. We computed the global LA wall area change ratio, termed the global LA area strain (GLAS), during both the reservoir phase (GLAS-r) and contraction phase (GLAS-ct). The LVDP at end-diastole (LVEDP) and mean LVDP (mLVDP) were measured with a catheter-tipped micromanometer in each patient. GLAS-r and GLAS-ct were significantly correlated with both mLVDP (r=−0.70 [P<0.001] and r=0.71 [P<0.001], respectively) and LVEDP (r=−0.63 [P<0.001] and r=0.65 [P<0.001], respectively). In receiver operating characteristic curve analysis, the optimal cut-off values for diagnosing elevated LVEDP (≥16 mmHg) were 75.7% (sensitivity 83.3%, specificity 77.8%) for GLAS-r and −43.1% (sensitivity 90.0%, specificity 80.0%) for GLAS-ct. Similarly, for diagnosing elevated mLVDP (≥12 mmHg), the cut-off values were 63.6% (sensitivity 88.9%, specificity 80.3%) for GLAS-r and −26.2% (sensitivity 66.7%, specificity 97.0%) for GLAS-ct.Conclusions: We showed that 3D-STE-derived GLAS values could be used to non-invasively diagnose elevated LV filling pressure.

She Has a Big and Weak Heart

Abstract Background: Acromegaly is a rare clinical syndrome caused by excessive production of growth hormone. The incidence rate is 3 to 4 cases per million people per year. It is a sporadic disease seen in middle-aged adults. Anterior pituitary adenoma secreting the growth hormone (GH) is the most common etiology. Other rare causes include hypothalamic and neuroendocrine tumors. Treatment modalities include surgical, radiotherapeutic and pharmacological with a goal to reduce or remove the tumor, prevent recurrences, and improve comorbidities. The persistent hypersecretion of GH and insulin-like growth factor-1 (IGF-1) leads to an overgrowth in many tissues, including connective tissue, cartilage, bone, skin, and visceral organs. Cardiovascular disease is one of the critical systemic complications resulting in about 60% of the deaths. The cardiovascular manifestations include hypertension, cardiomyopathy (CMP), congestive heart failure, and arrhythmias. Our patient presented with congestive heart failure and dilated CMP in the setting of undiagnosed Acromegaly. Clinical Case: 45 -year old Caucasian lady presented with complaints of worsening shortness of breath, chest tightness, and palpitations for one month. Past medical history includes hypertension, type 2 diabetes mellitus, obesity, and hyperlipidemia. She was diagnosed with dilated CMP in her early 30s, AICD placement seven years ago and normal cardiac catheterization three years ago. On physical exam, she was found to have an enlarged nose and bibasilar crackles. Vitals were stable and proBNP: 4,699 (1-150 pg/ml). ECHO revealed EF of 30-35%, severely dilated left ventricle. Cardiac catheterization showed severely decreased left ventricular systolic dysfunction and elevated LVEDP. Further workup - GH: 16 (&amp;lt;10 ng/ml) and IGF-1: 637 (62 - 205 ng/ml), A1C 13.2%. Pituitary MRI showed a 1.6 cm macroadenoma, extending to the right cavernous sinus border with a deviation of the pituitary stalk to the left. On neurosurgical evaluation, she was considered to be a poor surgical candidate due to her underlying CMP. Currently, she is in the process of getting started on oral octreotide treatment. Conclusion: Cardiovascular disease is the most captious complication and a leading cause of mortality in Acromegaly patients. The subtle clinical presentation results in a diagnostic delay for 5-10 years. A careful review of history and physical examination is vital to identify acromegalic features in non-ischemic DCM. Early diagnosis with prompt treatment has shown improvement in cardiac function and reduced mortality. This case underscores the importance of considering Acromegaly as one of the differentials in patients with dilated cardiomyopathy.

Abstract 15351: Changes in Left Ventricular End-diastolic Pressure Following Alcohol Septal Ablation in Hypertrophic Obstructive Cardiomyopathy

Background: LVEDP is a representation of left ventricular diastolic function. An increased LVEDP correlates to decreased compliance and increased left ventricular workload, which can be seen in HOCM. In HOCM, the interventricular septum is hypertrophied creating a LVOT obstruction and elevated LVEDP. ASA induces a targeted septal infarction to reduce the size of the septum and relieve the LVOT obstruction. Non-targeted infarction in a MI can increase LVEDP. Our study aims to determine the immediate effect of ASA on LVEDP in HOCM patients. It is hypothesized that ASA immediately reduces LVEDP. Methods: Retrospective study of 113 patients where pre and post-ablation LVEDP were compared. LVEDP was measured at the end-expiratory R wave of the ECG tracing during the procedure. LVEDP measurements were recorded at the post-“a” wave points at the immediate start of the procedure (Group A), prior to the alcohol injection under mild sedation (Group B), and at the conclusion of the successful ablation (Group C). Results: Groups A, B, and C were compared using two-tailed t-tests. We found no statistical difference between groups A and B (mean A=31.34 vs. mean B=31.54; p=0.695). LVEDP was significantly lower in group C when compared to group A (mean A=31.34 vs. mean C=25.82; p=6.525E-9). LVEDP was also significantly lower in group C when compared to group B (mean B=31.54 vs. mean C=25.82; p=4.047E-9). A linear regression model showed no significant correlation between LVEDP and LVOT gradient reduction following ASA (R 2 =0.0258, Significance F=0.0891). Conclusion: This data supports our hypothesis that ASA immediately reduces LVEDP despite inducing an infarct of the septal myometrium. There is no effect of sedation on LVEDP during the procedure. Since LVEDP reduction does not seem to correlate with LVOT gradient reduction, the reduction in LVEDP is likely related to other hemodynamics improvements including reduction in mitral regurgitation and immediate improvement in diastolic function. Future studies can include evaluating a correlation between LVEDP reduction and immediate hemodynamic changes. They could also evaluate a correlation between the immediate drop in LVEDP and long-term outcomes to predict the prognosis of HOCM patients based on their ASA outcomes.

Metabolic syndrome contributes to the pulmonary arterial dysfunction in pulmonary hypertension in heart failure with preserved ejection fraction

Abstract Background Many Heart Failure with preserved Ejection Fraction (HFpEF) patients have metabolic syndrome and develop Exercise Induced Pulmonary Hypertension (EIPH). The pathogenesis of EIPH in HFpEF remains unclear as there is no rodent model. As the SGLT2 inhibitor Empagliflozin improves clinical outcome in patients with type 2 diabetes and cardiovascular risk, we tested its effect on EIPH in a novel rat model of HFpEF. Methods Obese ZSF1 (HFpEF model) with leptin receptor mutation have metabolic syndrome and received the VEGF-inhibitor SU5416 to stimulate PH (Obese + Sugen). Half also received Empagliflozin (0.2 mg/kg/day) in drinking water from 8 to 22 weeks old. Lean ZSF1 lacking the mutation served as controls. During treadmill exercise, right/left ventricle (RV/LV) hemodynamics were evaluated via catheters. Pulmonary artery vascular smooth muscle cells (PAVSMC) prepared from normal or diabetic patients were cultured in standard media, or with Palmitate acid, Glucose and Insulin (PGI) to induce metabolic stress. Flow cytometry was used to evaluate reactive oxygen species (ROS) in mitochondria (Mitosox) or cytoplasm (CellROX). Results Relative to Lean, Obese + Sugen had increased body weight and HgA1C (Fig. 1A). Relative to Lean and at rest, Obese + Sugen showed mildly elevated RVSP and LVEDP. After exercise, LVSP and LVEDP rose similarly in Lean and Obese + Sugen. However, after exercise, Obese + Sugen showed a markedly greater increase in RVSP and exercise intolerance consistent with EIPH (Fig. 1B). In MR imaging of PA, Lean showed dobutamine (5 μg/kg/min)-induced PA dilation, which was not seen in Obese + Sugen (Fig. 1C). Protein levels of sGCβ1 (key regulator of PA relaxation) and its transcription factor (NFYA) both were decreased in PA from Obese + Sugen relative to Lean (Fig. 1D). Obese + Sugen + SGLT2 inhibitor treated rats showed marked improvements metabolic syndrome (body weight, HgA1c), exercise induced increase in RVSP, PA response to dobutamine, and increased NFYA and sGCβ1 expression (Fig. 1A–D). We observed greater ROS-induced DNA damage (8-OHdG staining) (Fig. 1E) and mitochondrial complex I, III, and IV activity in Obese + Sugen PA that was normalized in Obese + Sugen + SGLT2 inhibitor (Fig. 1F), suggesting a role of ROS in EIPH. Control human PAVSMC treated with PGI media showed elevated cytoplasmic and mitochondrial ROS, associated with increased mitochondrial complex I, III, IV and V activity (Fig. 1F, G). PGI media also accelerated the degradation of NFYA RNA and protein level in a manner mimicked by H2O2, and prevented by catalase/SOD (Fig. 1H, I), suggesting PGI-induced ROS enhanced NFYA degradation. Diabetic human PAVSMCs cultured in normal media resembled PGI-treated normal cells with respect to sGCb1 and NFYA expression, and in response to catalase/SOD (Fig. 1H, I). Conclusions In this PH-HFpEF model, metabolic syndrome contributes to PA dysfunction and EIPH through mitochondrial dysfunction and enhanced ROS, which were improved by Empagliflozin treatment. Figure 1 Funding Acknowledgement Type of funding source: None

METASTATIC PULMONARY CALCIFICATION: A RARE CAUSE OF PULMONARY HYPERTENSION

SESSION TITLE: Fellows Pulmonary Vascular Disease Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: Metastatic calcification is seen at autopsy in 60-75% of CKD patients on hemodialysis (HD) due to increased calcium phosphate product (normal 40 mg2/dl2; MPC >70 mg2/dl2) (1,2). Metastatic pulmonary calcification associated with pulmonary hypertension (PH) is rare. We present a case of MPC associated combined postcapillary and precapillary PH (CpcPH). CASE PRESENTATION: A 58-year-old woman with SLE, CTD-ILD (FVC 64%, TLC 56 %), ESRD on HD since 2008 and diastolic heart failure was admitted to the hospital with worsening dyspnea, leg edema and orthopnea. Her calcium phosphate product was 61. CT chest showed diffuse ground glass opacity with mosaic perfusion, enlarged pulmonary artery (PA 4.3 cm) and chest wall calcifications. Echocardiogram showed grade 3 diastolic dysfunction, severely dilated left atrium and elevated right ventricular systolic pressure. Heart catheterization showed mean PA pressure 62 mm Hg, PA wedge pressure 29 mm Hg, transpulmonary gradient (TPG) 33, diastolic pulmonary gradient (DPG) 11, pulmonary vascular resistance 9 WU, LV end diastolic pressure 27 mm Hg, cardiac output 3.6, cardiac index 2.1. Given her severe PH, low CI and NYHA functional class IV, she was started on inhaled treprostinil with improvement in leg edema and orthopnea at 6-month follow up. DISCUSSION: Hyperphosphatemia in ESRD causes increased calcium phosphate product leading to calcium crystallization. Metastatic calcifications are usually seen in lamina propria of stomach, lung alveoli, renal tubules and interstitium(2). Acidosis between HD sessions causes leaching of calcium from bone, leading to deposition during post dialysis alkalosis. Uremia alters the configuration of tissue protein, rendering them more calcifiable. Three main CT patterns of MPC include centrilobular ground glass nodules, dense consolidation and small dense nodules(1). It is usually peripheral in distribution with upper lung zone dominance due to increased alkalinity (higher V/Q ratio causing low PaCO2) causing calcium salt deposition. Vascular calcification in chest and abdominal wall is a common finding as noted in our case. 30-50% of CKD and ESRD patients have PH. Vascular calcification can affect pulmonary arterial capacitance (low PAC in our case 0.81) and increase RV afterload. In this case, contributing factors to her PH are elevated LVEDP, ILD and ESRD (WHO group II, III and V). TPG >12 and DPG >7 suggested pulmonary vascular remodeling from shear stress and downstream pressure. This is an interesting case of MPC with associated PH. Initiation of the pulmonary vasodilator treprostinil reduced her PVR allowing for a better coupling of the RV-PA system. CONCLUSIONS: Treatment of MPC includes intensification of HD sessions and use of calcium and phosphate binders. In this case, inhaled pulmonary vasodilators for treatment of CpcPH after medical treatment optimization of other co-morbidities led to symptomatic improvement. Reference #1: Metastatic pulmonary calcification: HRCT findings in 23 cases, Radiol Bras.2017 Jul-Aug; 50(4): 231–236 Reference #2: Metastatic pulmonary calcification: State-of-the-art review focused on imaging findings, Respiratory Medicine Feb 2014 (108): 668-676 Reference #3: Pulmonary hypertension with extensive calcification in small pulmonary vessels and alveolar capillary wall in a chronic hemodialysis patient, Journal of Cardiology Cases 8 (Feb 2013) e13–e16 DISCLOSURES: No relevant relationships by Moises Cossio, source=Web Response No relevant relationships by Domingo Franco-Palacios, source=Web Response No relevant relationships by Kushagra Gupta, source=Web Response No relevant relationships by Shahzad Hussain, source=Web Response No relevant relationships by Venkateswara Kollipara, source=Web Response No relevant relationships by Toribiong Uchel, source=Web Response

Skeletal Muscle Capillary Hemodynamics in Rats with Heart Failure with Preserved Ejection Fraction

The cardinal symptom in heart failure with preserved ejection fraction (HFpEF) is severe exercise intolerance. Limited understanding of HFpEF pathophysiology has precluded the development of effective therapies. We examined the effects of HFpEF on nitric oxide (NO)‐mediated regulation of skeletal muscle capillary hemodynamics. The hypothesis was tested that HFpEF would reduce the proportion of capillaries supporting continuous red blood cell (RBC) flow and impair microvascular hemodynamics in perfused capillaries partly via deteriorations in NO‐mediated function.METHODSIntravital microscopy was used to evaluate the resting spinotrapezius muscle in old male Spontaneously Hypertensive Rats (SHR; n=7) and healthy normotensive Wistar‐Kyoto rats (WKY; n=5). Presence of HFpEF in SHR rats was determined using in vivo (echocardiography and micromanometer) and post‐mortem evaluation of cardiac structure and function. Capillary lumen diameter (dcap), %RBC‐perfused capillaries, and RBC flux (fRBC), velocity (VRBC) and hematocrit (Hctcap) were assessed at physiological sarcomere lengths (2.8±0.1 μm) under control (CON) and non‐selective NO synthase blockade (L‐NAME; 1.5 mM) superfusion conditions.RESULTSCompared to WKY, SHR had elevated left ventricular end‐diastolic pressure (LVEDP; SHR: 11.3±1.3, WKY: 6.9±1.1 mmHg; P&lt;0.05), preserved LV ejection fraction (EF; 76±3 and 81±4%; P&gt;0.05) and fractional shortening (FS; 41±3 and 46±4%; P&gt;0.05), and increased LV mass/body mass (2.54±0.09 and 2.01±0.04 mg/g; P&lt;0.05). As expected, mean arterial pressure was higher in SHR compared to WKY under CON (139±14 and 93±5 mmHg, respectively; P&lt;0.05) with no changes produced by L‐NAME (P&gt;0.05). There were no differences in the %RBC‐flowing capillaries between SHR and WKY under CON (88±2 and 92±2%; P&gt;0.05) or L‐NAME (P&gt;0.05). In RBC‐flowing capillaries under CON, SHR had lower fRBC (10.9±1.3 and 13.7±1.4 cells/s) and VRBC (142±14 and 185±11 μm/s) than WKY (P&lt;0.05 for both). L‐NAME reduced fRBC in WKY (7.6±0.6; P&lt;0.05) but not SHR (10.0±1.0 cells/s; P&gt;0.05). Moreover, L‐NAME induced a greater magnitude of VRBC reduction in WKY (42±3%) than SHR (12±5%; P&lt;0.05). No differences in Hctcap were observed between SHR and WKY under CON (0.25±0.01 and 0.23±0.02) or L‐NAME (P&gt;0.05 for all). Similarly, no differences in dcap were seen between SHR and WKY under CON (4.9±0.1 and 5.1±0.1 μm) or L‐NAME (P&gt;0.05 for all).CONCLUSIONSSHR displayed several cardiovascular alterations consistent with HFpEF, including elevated LVEDP, preserved EF and FS, and increased LV mass/body mass. Although not impacting dcap or Hctcap, SHR showed marked reductions in fRBC and VRBC resulting partly from impaired NO‐mediated function. These alterations in microvascular O2 perfusion likely contribute to exercise intolerance in HFpEF. These data thus reveal important mechanistic clues into muscle dysfunction in this disease and identify the skeletal muscle capillary network as a potential therapeutic target in HFpEF.Support or Funding InformationNIH HL‐2‐108328

Severe Pulmonary Hypertension in the Setting of Complex Structural Heart Disease

Pulmonary hypertension (pHTN) complicating structural heart disease leads to distinct diagnostic and management dilemmas. We present a case of severe pulmonary hypertension in the setting of perimembranous VSD and severe AS. 76 yo female with restrictive VSD and severe AS presented with heart failure. Cardiac findings included RV heave and AS murmur. TTE revealed normal EF with severe pHTN, severe RV dysfunction, and severe AS. Her perimembranous septum was aneurysmal, with systolic jet velocity of 4.5 m/s. There was no CAD. RHC demonstrated PAP of 96/38/57 mmHg, PVR of 7.2 WU, PCWP 23 mmHg, CI of 3.04, and Qp/Qs of 1.1. The PCWP and PVR indicated pre- and post-capillary pHTN due to longstanding AS. She was deemed inoperable and was high risk for TAVR given aortic annular continuity with the VSD and ∼25% annular deficiency. There was concern that her elevated LVEDP was masking Eisenmenger physiology, and that relieving the AS may precipitate hypoxia. Balloon aortic valvuloplasty (BAV) was performed as bridge to decision. This enabled assessment of the integrity of the aortic annulus, the pulmonary pressure response to LV unloading, and development of right to left shunting after a decrease in LVEDP. Successful BAV was performed, and the patient was discharged. Following improvement in both PA pressures and her symptoms, a TAVR was offered. A self-expanding valve was selected to minimize risk of annular rupture. After successful deployment, her PAP were 78/42/54 and PCWP 23. She was diuresed and discharged. Our case highlights important points in management of such complex patients with pHTN. Careful evaluation of hemodynamics is paramount in guiding decision making. The preserved PAPi with minimal shunting suggested the VSD was not significantly contributing to the severe pHTN. Additionally, BAV plays an important role as a bridge to determine potential response to TAVR. Although patients with WHO II pHTN can develop an irreversible pre-capillary component, such assessment can only be made following durable reduction in LVEDP. Lastly, interdisciplinary patient care is essential. Successful management of our patient required input from a multidisciplinary team consisting of pulmonology, structural cardiology, critical care cardiology and heart failure.

381 Novel Combined Algorithm to Assess Left Ventricular Diastolic Function and Filling Pressures: Correlation With Filling Pressures and Outcomes

A novel combined algorithm has been proposed utilising guideline recommended diastolic parameters that can be applied to all patients regardless of LVEF. This study sought to determine the haemodynamic and prognostic validity of this new algorithm in patients with myocardial infarction(MI). A retrospective single centre study involving 277 patients with a first-ever MI was performed. Outcomes data were obtained from the national death registry. Echocardiography was performed early post-admission for all patients. Significant diastolic dysfunction (DD) was defined was grade 2/3 DD according to the novel algorithm. Haemodynamic correlation involved 54 patients who underwent either same-day or simultaneous cardiac catheterisation or echocardiography. With respect to outcomes, there were a total of 40 MACE events (median follow-up of 2 years). Significant DD was significantly associated with MACE on Kaplan-Meier analysis: log-rank χ2 22.08(p<0.001). In a multivariate Cox proportional hazards model incorporating significant clinical factors (age, chronic kidney disease) and LVEF, significant DD was the most powerful predictor of outcomes (HR 2.71[95% CI 1.28-5.71]; p=0.008). In the haemodynamic study, LVEDP was noted to be elevated in patients with significant DD: mean LVEDP 21.1+7.9mmHg versus 13.2+6.1mmHg (p=0.001). Receiver operating curves showed an area under the curve of 0.814(p<0.001) for assessing elevated LVEDP. The calculated sensitivity, specificity, positive predictive value(PPV) and negative predictive value for LVEDP>15 mmHg was 41.7%, 87.1%, 78.9%, and 56.3% respectively. Significant DD assessed using the novel combined algorithm (i) was an independent predictor of clinical outcomes and (ii) detects elevated LVEDP with a high specificity and PPV.

Hemodynamic Validation of the E/e’ Ratio as a Measure of Left Ventricular Filling Pressure in Patients With Non-ST Elevation Myocardial Infarction

The E/e' ratio has an established role in the assessment of left ventricular filling pressure (LVFP) in stable patients, but its accuracy in acute myocardial ischemia is less well established. The aim of this study was to validate the relation between the E/e' ratio and invasively measured LVFP in patients with non-ST elevation myocardial infarction (NSTEMI). A total of 120 unselected patients with NSTEMI underwent cardiac catheterization with measurement of left ventricular end-diastolic pressure (LVEDP; elevated ≥15 mm Hg) and Doppler echocardiography with either simultaneous (n = 30) or same-day (n = 90) measurement of E/e'. Patients were aged 64.1 ± 11.8 years, 72% were male and mean left ventricular ejection fraction was 48.0 ± 20.9%. Septal, lateral, and average E/e' ratios all showed a significant correlation with LVEDP (Pearson's r: 0.42, 0.43, 0.48, respectively [all p <0.001]). Receiver operating characteristics curves showed an area under the curve of 0.72, 0.72, and 0.75 (all p <0.001) for septal, lateral, and average E/e', respectively. The sensitivity, specificity, positive (PPV), and negative (NPV) predictive values for the guideline-recommended threshold of average E/e' >14 for elevated LVEDP was 27%, 93%, 79%, and 44%, respectively. Utilizing lower E/e' boundaries of 6, 7, and 8 for lateral, average, and medial E/e', respectively, improved the NPV to ≥80% for each parameter. In conclusion, the E/e' ratio is a robust measure of LVFP during acute NSTEMI using upper and lower thresholds to achieve a high PPV and NPV, respectively, with the use of adjunctive guideline-recommend measures required in patients with nonconclusive E/e'.

Usefulness of Echocardiography/Doppler to Reliably Predict Elevated Left Ventricular End-Diastolic Pressure in Patients With Pulmonary Hypertension

The ability of echocardiography (echo)/Doppler to predict elevated left ventricular (LV) end-diastolic pressure (EDP) specifically among patients with pulmonary hypertension is not well defined. This was a retrospective analysis of 161 patients referred to a specialized pulmonary hypertension clinic. A model based on an American Society of Echocardiography (ASE)/European Association of Echocardiography (EAE) joint statement was evaluated, and a new model was developed using univariate linear regression and multivariable logistic regression for potentially better prediction of elevated LVEDP. The study cohort had a median pulmonary arterial pressure was 34.0mm Hg and pulmonary vascular resistance was 3.7 Wood units; 81 patients (51%) had LVEDP >15mm Hg on invasive testing. Doppler E/A, E/e' (septal, lateral, and average), e'/a' (lateral and average), and left atrial volume and diameter all had significant correlation with LVEDP (p <0.05). The ASE/EAE model performed poorly (sensitivity 54% and specificity 66%) for detecting elevated LVEDP. Only echo/Doppler grade 3 diastolic dysfunction had an LVEDP significantly different from other grades (grade 0 to 2, median 15mm Hg, interquartile range 13 to 22mm Hg; grade 3, median 22mm Hg, interquartile range 19 to 32mm Hg; p <0.01). An experimental model was statistically significant in its prediction of elevated LVEDP (area under the receiver operating characteristic curve 0.7, p <0.001) but demonstrated poor performance (sensitivity 67% and specificity 61%). In conclusion, numerous echo/Doppler measurements correlate with elevated LV filling pressure. However, both the ASE/EAE model and our experimental model had poor test performance that did not permit confident identification of elevated LVEDP.

Characterisation of a Large Animal Model of Heart Failure with Preserved Ejection Fraction (HFpEF)

Background: The failure of the development of treatment for HFpEF is the result of key factors: critically, HFpEF is a disease of ageing in combination with other factors including atrial fibrillation, and the effect of potential treatments for HFpEF can only be validated pre-clinically in-vivo using large animal models, to effectively prove effects on heart function. Aim: To characterise a large animal model of HFpEF and determine applicability for pre-clinical therapeutic research. Methods: Eight aged and eight young female sheep (ewes) were anaesthetised and underwent transthoracic echocardiography and were instrumented with a left ventricular pressure transducer catheter. Left ventricular biopsies were taken for histological and molecular analysis. Results: Sheep (ewes) aged >6yrs had a preserved LVEF 73 ±8% vs young, with marked LV hypertrophy, significant myocardial fibrosis compared to young animals and elevated LVEDP (aged: 10.3 ± 1.5 vs young: 3.8 ± 0.9 mmHg, p<0.05). Conclusions: This acute study has characterised a clinically relevant, large animal model of HFpEF.

E/E’ Ratio as a Noninvasive Measure of Left Ventricular Filling Pressure in Patients with Non-ST-elevation Acute Coronary Syndromes (NSTEACS)

Background: The E/e’ ratio has an established role in the assessment of left ventricular filling pressures (LVFP) in stable patients. There is limited data on the assessment of LVFP with the E/E’ in patients with NSTEMI. We sought to perform an invasive haemodynamic validation study with near-simultaneous measurement of Doppler echocardiographic parameters and invasively measured LVFP in patients with NSTEMI. Methods: A total of 29 unselected patients with NSTEMI underwent a limited transthoracic echocardiogram on the cardiac catheterisation table immediately prior to coronary angiography. Mitral inflow E-wave and tissue Doppler derived E’ at the septal and lateral mitral annulus was measured. Invasive measurement of LVFP was then performed with a pigtail catheter in mid shallow expiration. Results: The mean age of patients was 64.1 years, with 72% males. The mean LVEF was 52%. Angiographic findings included 3-vessel disease in 12.5% and LAD culprit lesions in 25%. Septal E/E’ had a good correlation with LVEDP (Spearman's rho 0.603,p=0.001). The lateral E/E’ also had a good correlation with LVEDP (Spearman's rho 0.548,p=0.002). In a multivariate analysis for the predictors of elevated LVEDP(≥16 mmHg) incorporating E velocity, E/A ratio, deceleration time (DT) and septal and lateral E/E's, the septal E/E’ was the only independent predictor (OR = 11.9(95%CI 9.4-14.0), p=.047). A septal E/E’ cutoff of 15 identified 5/12 cases of LVEDP >16 mmHg whilst an E/E’ cutoff identified 10/12 cases of LVEDP >16 mmHg. Conclusions: Septal E/E’ ratio is a valid non-invasive assessment of elevated filling pressures in patients with NSTEMI.

Levosimendan reduces myocardial damage and improves cardiodynamics in streptozotocin induced diabetic cardiomyopathy via SERCA2a/NCX1 pathway

AimsDiabetic cardiomyopathy (DCM) is one of the most common causes of mortality. Its pathophysiology is not fully understood and involve number of factors including, cardiovascular and metabolic disorders. The present study was designed to study the pathogenesis of DCM and to explore the effects of levosimendan along with either ramipril or insulin in the long term management of DCM. Materials and methodsStreptozotocin (STZ) was used to develop DCM in Wistar rats at the dose of 25mg/kg body weight for three consecutive days. Rats were randomly divided into 9 groups and treatments were started after 2weeks of STZ administration. Key findingsPersistent hyperglycemia was observed in STZ treated rats, leading to significant contractile dysfunction as evidenced by decreased left ventricular pressure (LVP), +LV (dp/dt), −LV (dp/dt) as well as elevated Tau and LVEDP. Marked myocardial damage such as fibrosis, increased wall tension, depletion of contractile proteins were observed as evidenced by increased levels of TGF-β, BNP, cTroponin-I, as well as decreased expression of SERCA2a and NCX1 proteins in diabetic rats. The levosimendan alone and also in combination with either ramipril or insulin significantly normalized the myocardial dysfunctions developed during the course of persistent hyperglycemia. SignificanceThe study suggests that levosimendan treatment improves cardiac dysfunction significantly. Its combined use with ramipril proves better than with insulin in correcting myocardial performance as well as reduction in myocardial damage.

Relationship of prolonged global and regional central circulatory transit time with hemodynamics

Methods Forty nine subjects undergoing clinically indicated right and left heart cardiac catheterization were prospectively recruited to undergo MRI in a 1.5T scanner. First pass perfusion using steady state free precession saturation recovery sequence was performed with gadolinium infusion at 0.01 mmol/kg. Global TT was defined as the time between the peaks of time intensity curves between the right atrium and the ascending aorta. Segmental TT included TT between right atrium to pulmonary artery (right heart TT), pulmonary artery to left atrium (pulmonary TT), or left atrium to ascending aorta (left heart TT). All TTs were normalized to heart rate. Multivariate regression analysis was performed to delineate the relationship of hemodynamic parameters measured during cardiac catheterization to TT. Receiver operating characteristic (ROC) analyses were performed to assess ability of global and segmental TT to predict elevated LVEDP.