Left Heart Pressures Research Articles

Equine exercise-induced pulmonary hemorrhage: the role of high left-heart pressures secondary to exercise-induced hypervolemia, and high inspiratory pressures.

Exercise-induced hypervolemia is normal in racehorses. Stress failure of the blood-gas barrier causes EIPH and occurs when the transmural pulmonary capillary (Pcap)-alveolar pressure difference (Ptm) exceeds the barrier's stress failure threshold. Why Pcap increases is incompletely understood. We hypothesized that alterations in blood volume (BV) affect left ventricular (LV) and pulmonary arterial wedge (PAW) pressures, and Pcap, and correspondingly affect EIPH severity. Six thoroughbreds with EIPH underwent treadmill exercise at the same speed (≈11.9m/s [11.1, 12.2]; median [IQR]) before (≈119%V̇O2max; B), 2hr after 14L depletion of blood (≈132%V̇O2max; D) and 2hr after reinfusing the blood (≈111%V̇O2max; R). LV, pulmonary arterial (PAP), PAW and intrapleural (Ppl) pressures were measured throughout exercise. Pcap = (PAP+PAW)/2 and Ptm = Pcap - Ppl. EIPH severity was assessed 60min post-exercise by tracheoendoscopy (EIPHgrade) and bronchoalveolar lavage erythrocyte count (BALRBC). A mixed-effect model and Tukey post-hoc test analyzed effects of BV changes on LV, PAW, Pcap, Ppl, Ptm and EIPH. p≤0.05 was significant. EIPH severity was affected by BV (EIPHgrade: p=0.01, BALRBC: p=0.003). Peak Ptm was not different between B (146mmHg [140; 151]) and R (151mmHg [137; 160]) but was lower for D (128mmHg [127; 130]; B: p=0.005, R: p=0.02). LV end diastolic pressure (LVED) was correlated with maxPcap (r2=0.52, p=0.001). Ppl was unaffected by changes in BV. Vascular pressures and Ppl fluctuated constantly during exercise and independently influenced Ptm. Circulating BV but not exercise intensity had a major effect on LVED, Pcap and Ptm, and was correlated with EIPH severity in thoroughbred racehorses (r2=0.48, p=0.001).

Simple model of pulmonary hypertension secondary to left heart pressure overload induced by partial intravascular occlusion of the ascending aorta.

Pulmonary hypertension is a group of diseases characterized by elevated pulmonary artery pressure and pulmonary vascular resistance with significant morbidity and mortality. The most prevalent type is pulmonary hypertension secondary to left heart disease (PH-LHD). The available experimental models of PH-LHD use partial pulmonary clamping by technically nontrivial open-chest surgery with lengthy recovery. We present a simple model in which the reduction of the cross-sectional area of the ascending aorta is achieved not by external clamping but by partial intravascular obstruction without opening the chest. In anesthetized rats, a blind polyethylene tubing was advanced from the right carotid artery to just above the aortic valve. The procedure is quick and easy to learn. Three weeks after the procedure, left heart pressure overload was confirmed by measuring left ventricular end-diastolic pressure by puncture (1.3 ± 0.2 vs. 0.4 ± 0.3 mmHg in controls, mean ± SD, P < 0.0001). The presence of pulmonary hypertension was documented by measuring pulmonary artery pressure by catheterization (22.3 ± 2.3 vs. 16.9 ± 2.7 mmHg, P = 0.0282) and by detecting right ventricular hypertrophy and increased muscularization of peripheral pulmonary vessels. Contributions of a precapillary vascular segment and vasoconstriction to the increased pulmonary vascular resistance were demonstrated, respectively, by arterial occlusion technique and by normalization of resistance by a vasodilator, sodium nitroprusside, in isolated lungs. These changes were comparable, but not additive, to those induced by an established pulmonary hypertension model, chronic hypoxic exposure. Intravascular partial aortic obstruction offers an easy model of pulmonary hypertension induced by left heart disease that has a vasoconstrictor and precapillary component.NEW & NOTEWORTHY We present a new, simple model of a clinically important type of pulmonary hypertension, that induced by left heart failure. Left ventricular pressure overload is induced in rats by inserting a blinded cannula into the ascending aorta via carotid artery access. This partial intravascular aortic obstruction, which does not require opening of the chest and prolonged recovery, causes pulmonary hypertension, which has a precapillary and vasoconstrictor as well as a vascular remodeling component.

Abstract 12977: Prevalence and Incidence of Diastolic Dysfunction in Patients With Functional Tricuspid Regurgitation

Introduction: Isolated functional tricuspid regurgitation (FTR) in the absence of structural heart disease may develop secondary to elevation in left heart pressures caused by left ventricular diastolic dysfunction (DD), as in heart failure with preserved ejection fraction (HFpEF). FTR may also herald the presence of occult DD or indicate greater risk for new-onset DD. However, prevalence and incidence of diastolic dysfunction (DD) in isolated FTR have not been studied. Aims: Investigate the prevalence and incidence of DD across the different severities of FTR of unclear cause. Methods: Adults with normal EF and without structural heart disease undergoing echocardiography at a tertiary medical center with a repeat study ≥6 months from baseline were identified. Severe DD was defined by ≥3/4 abnormal DD parameters (medial e’, medial E/e’, tricuspid regurgitation velocity, left atrial volume index) and moderate DD by ≥2. Results: Among 30,428 patients (median age 60; 50% women), FTR was absent in 73%, mild in 22%, moderate in 4%, and severe in 0.4%. Severe DD was present in 2%, 5%, 11%, and 13% patients, respectively, (p&lt;.001) and moderate DD in 9%, 19%, 31%, and 48%, respectively (p&lt;.001). The association of DD with increasing FTR was independent of all clinical characteristics. Over median 3.0 (IQR 1.5-5.4) years, incident severe and moderate DD developed more frequently with increasing FTR severity ( Figure) . Findings were confirmed in a propensity-matched subset where patients were matched for age, sex, BMI, atrial fibrillation, and comorbidities and in patients without lung disease or ≥moderate right ventricular enlargement. Conclusions: Patients with FTR of undefined etiology commonly have DD suggesting the presence of underlying left heart disease. Patients without apparent DD or HF at baseline who have FTR remain at significantly increased risk of developing DD over follow-up and may be a target population for therapies to prevent progression to clinical HFpEF.

Pulmonary Hypertension in Left Heart Diseases: Pathophysiology, Hemodynamic Assessment and Therapeutic Management.

Pulmonary hypertension (PH) associated with left heart diseases (PH-LHD), also termed group 2 PH, represents the most common form of PH. It develops through the passive backward transmission of elevated left heart pressures in the setting of heart failure, either with preserved (HFpEF) or reduced (HFrEF) ejection fraction, which increases the pulsatile afterload of the right ventricle (RV) by reducing pulmonary artery (PA) compliance. In a subset of patients, progressive remodeling of the pulmonary circulation resulted in a pre-capillary phenotype of PH, with elevated pulmonary vascular resistance (PVR) further increasing the RV afterload, eventually leading to RV-PA uncoupling and RV failure. The primary therapeutic objective in PH-LHD is to reduce left-sided pressures through the appropriate use of diuretics and guideline-directed medical therapies for heart failure. When pulmonary vascular remodeling is established, targeted therapies aiming to reduce PVR are theoretically appealing. So far, such targeted therapies have mostly failed to show significant positive effects in patients with PH-LHD, in contrast to their proven efficacy in other forms of pre-capillary PH. Whether such therapies may benefit some specific subgroups of patients (HFrEF, HFpEF) with specific hemodynamic phenotypes (post- or pre-capillary PH) and various degrees of RV dysfunction still needs to be addressed.

Perioperative right ventricular dysfunction in adult patients undergoing non-complex cardiac surgery: diagnosis and management

Even though there is no precise consensus on definition of the right ventricular dysfunction and the right ventricular failure, their reported incidence after cardiac surgery ranges from 0.04% to 2.9%. Right ventricular dysfunction is clinically important because it has been consistently shown to have a negative impact on the perioperative outcomes. In this article we explore current evidence on perioperative diagnosis and management of adult patients with right ventricular dysfunction who are undergoing non-complex cardiac surgery. We propose criteria for the right ventricular dysfunction, describe its pathophysiological mechanisms, diagnostic and therapeutic options as well as current challenges. The function of the right ventricle is determined by preload, afterload, contractility, ventricular interdependence, and heart rhythm. These five factors should all be assessed in a particular patient. Right ventricular dysfunction is not always easy to confirm. Transthoracic and transesophageal echocardiography are the mainstay of diagnosis. Also, clinical and laboratory findings should be considered especially when the patient approaches the extreme of right ventricular dysfunction spectrum—right ventricular failure. Right ventricular failure should be anticipated, and management focused on its prevention and treatment of the underlying cause. The clinical aim is to optimise the volume status, minimise the right ventricular afterload, optimise right ventricular free wall and interventricular septum performance, and to maximise the left heart pressure work. If the patient does not respond to conservative therapy, mechanical support should be promptly considered.

3-DIMENSIONAL CARDIOGENIC SHOCK SIMULATOR PHASE I: SUCCESSFUL DEVELOPMENT OF A LARGE ANIMAL CARDIOGENIC SHOCK MODEL

<h3>BACKGROUND</h3> Post-myocardial infarction (Post-MI) cardiogenic shock (CS) is a serious life-threatening condition that requires complex coordinated care. Despite this, early mortality remains as high as 50%, likely owing to still inadequate understanding of pathophysiology and the potential benefits of percutaneous ventricular assist devices (pVADs). Although all pVADs increase circulatory flow, they vary in their ability to help restore cardiac pump function. Additionally, shortcomings in terms of our understanding of the optimal timing of such devices in STEMI and shock algorithms likely contributes to the high mortality. Currently, preclinical pVAD evaluation is limited by the need for animal research where the induction of CS is often lethal before devices can be tested. We therefore plan to develop a high-fidelity simulator to facilitate device evaluation and help train clinical teams. The first phase to this program requires the elaboration of a stable animal post-MI CS model that can generate the physiologic data necessary for simulator validation. <h3>METHODS AND RESULTS</h3> Using 10 anesthetized 65-75kg female pigs, we sought to induce a large anterior infarct by percutaneous balloon occlusion of the left anterior descending artery with a provision for ethanol injection if CS was not observed within 2 hours of balloon occlusion. Continuous physiologic monitoring was ensured in order to record right and left heart and arterial pressures, mixed venous oxygen saturation, cardiac output, and serum lactate levels. Indices of myocardial contractility and relaxation were calculated at regular intervals. At the end of the experiment, Evans Blue was injected into the coronary circulation in order to determine the size of the myocardium at risk. The explanted heart was then stained with TTC mitochondrial stain and fixed with formaldehyde to determine the size of the infarct. A rate of survival of the anterior infarct of ≥50% and a rate of induction of CS in at least 50% of the survivors was considered necessary for the viability of the program. We successfully induced myocardial infarction in all 10 pigs and 5 pigs survived to develop cardiogenic shock. <h3>CONCLUSION</h3> While challenging, we successfully demonstrated that a large animal model of cardiogenic shock is possible and stable enough to generate the physiologic data necessary for the development of a CS simulator. The second phase will consist of the collection of detailed physiological data in a CS state with and without different pVAD support.

Vasodilator use in precapillary pulmonary hypertension with end stage kidney disease: A single center experience

Background and objectivesPulmonary hypertension is commonly seen in end stage kidney disease and is most commonly due to elevated left heart pressures. There is limited data about vasodilator use during the management of Group 1 pulmonary arterial hypertension in the context of those who also have or later developed end stage kidney disease. The objective of this study was to determine safety and efficacy of vasodilator therapy in precapillary pulmonary hypertension requiring renal replacement therapy. DesignThis was a single-center retrospective case series. Patients were identified from our Pulmonary Hypertension Clinic using a historical roster from 2012 to 2020. Patients were included if they >18 years of age, had Group 1 or Group 4 (precapillary) pulmonary hypertension on right heart catheterization, and also had end stage kidney disease requiring either intermittent hemodialysis or peritoneal dialysis. Results18 patients were identified with invasively confirmed Group 1 or Group 4 pulmonary hypertension and end stage kidney disease on renal replacement therapy. Scleroderma was the most common etiology for renal failure. 17 patients were treated with vasodilator therapy. Fifteen patients had paired right heart catheterizations that showed a significant decrease in mean pulmonary artery pressure and pulmonary vascular resistance. Therapy was relatively well tolerated but hypotension was common and midodrine was often helpful. Two patients had successful renal transplantation after starting vasodilator therapy. ConclusionWe found vasodilator therapy was reasonably well tolerated and associated with a drop in mean pressure and pulmonary vascular resistance in patients with end stage kidney disease on dialysis.

Adenine Nucleotide Translocase 1 Expression Modulates the Immune Response in Ischemic Hearts

Adenine nucleotide translocase 1 (ANT1) transfers ATP and ADP over the mitochondrial inner membrane and thus supplies the cell with energy. This study analyzed the role of ANT1 in the immune response of ischemic heart tissue. Ischemic ANT1 overexpressing hearts experienced a shift toward an anti-inflammatory immune response. The shift was characterized by low interleukin (IL)-1β expression and M1 macrophage infiltration, whereas M2 macrophage infiltration and levels of IL-10, IL-4, and transforming growth factor (TGFβ) were increased. The modulated immune response correlated with high mitochondrial integrity, reduced oxidative stress, low left ventricular end-diastolic heart pressure, and a high survival rate. Isolated ANT1-transgenic (ANT1-TG) cardiomyocytes expressed low levels of pro-inflammatory cytokines such as IL-1α, tumor necrosis factor α, and TGFβ. However, they showed increased expression and cellular release of anti-inflammatory immunomodulators such as vascular endothelial growth factor. The secretome from ANT1-TG cardiomyocytes initiated stress resistance when applied to ischemic wild-type cardiomyocytes and endothelial cells. It additionally prevented macrophages from expressing pro-inflammatory cytokines. Additionally, ANT1 expression correlated with genes that are related to cytokine and growth factor pathways in hearts of patients with ischemic cardiomyopathy. In conclusion, ANT1-TG cardiomyocytes secrete soluble factors that influence ischemic cardiac cells and initiate an anti-inflammatory immune response in ischemic hearts.

Implantation of an Innovative Intracardiac Microcomputer System for Web-Based Real-Time Monitoring of Heart Failure: Usability and Patients' Attitudes.

BackgroundHeart failure (HF) management guided by the measurement of intracardiac and pulmonary pressure values obtained through innovative permanent intracardiac microsensors has been recently proposed as a valid strategy to individualize treatment and anticipate hemodynamic destabilization. These sensors have potential to reduce patient hospitalization rates and optimize quality of life.ObjectiveThe aim of this study was to evaluate the usability and patients’ attitudes toward a new permanent intracardiac device implanted to remotely monitor left intra-atrial pressures (V-LAP, Vectorious Medical Technologies, Tel Aviv, Israel) in patients with chronic HF.MethodsThe V-LAP system is a miniaturized sensor implanted percutaneously across the interatrial septum. The system communicates wirelessly with a “companion device” (a wearable belt) that is placed on the patient’s chest at the time of acquisition/transmission of left heart pressure measurements. At first follow-up after implantation, the patients and health care providers were asked to fill out a questionnaire on the usability of the system, ease in performing the various required tasks (data acquisition and transmission), and overall satisfaction. Replies to the questions were mainly given using a 5-point Likert scale (1: very poor, 2: poor, 3: average, 4: good, 5: excellent). Further patient follow-ups were performed at 3, 6, and 12 months.ResultsUse and acceptance of the first 14 patients receiving the V-LAP technology worldwide and related health care providers have been analyzed to date. No periprocedural morbidity/mortality was observed. Before discharge, a tailored educational session was performed after device implantation with the patients and their health care providers. At the first follow-up, the mean score for overall comfort in technology use was 3.7 (SD 1.2) with 93% (13/14) of patients succeeding in applying and operating the system independently. For health care providers, the mean score for overall ease and comfort in use of the technology was 4.2 (SD 0.8). No significant differences were found between the patients’ and health care providers’ replies to the questionnaires. There was a general trend for higher scores in patients’ usability reports at later follow-ups, in which the score related to overall comfort with using the technology increased from 3.0 (SD 1.4) to 4.0 (SD 0.7) (P=.40) and comfort with wearing and adjusting the measuring thoracic belt increased from 2.8 (SD 1.0) to 4.2 (SD 0.4) (P=.02).ConclusionsDespite the gravity of their HF pathology and the complexity of their comorbid profile, patients are comfortable in using the V-LAP technology and, in the majority of cases, they can correctly and consistently acquire and transmit hemodynamic data. Although the overall patient/care provider satisfaction with the V-LAP system seems to be acceptable, improvements can be achieved after ameliorating the design of the measuring tools.Trial RegistrationClincalTrials.gov NCT03775161; https://clinicaltrials.gov/ct2/show/NCT03775161

Cine MRI detects elevated left heart pressure in pulmonary hypertension.

Cine magnetic resonance imaging (MRI) is an emerging modality for evaluating left ventricular (LV) motion/deformation patterns, which may have potential to identify LV dysfunctions underlying postcapillary pulmonary hypertension (PH). The aim of this study was to test the hypothesis that cine MRI-derived LV motion/deformation indices can be used to identify an elevated left heart pressure in PH. This was a retrospective study, which included 26 precapillary and 28 postcapillary PH patients (23 males, 58.9 ± 13.5 years old). All patients underwent right heart catheterization (the "reference standard") and cardiac MRI. Balanced steady-state free precession cine sequence acquired at 1.5 T was used. Cine MRI datasets were analyzed by using heart deformation analysis. LV motion/deformation indices were measured through 25 phases within a cardiac cycle. Peak LV displacement, velocity, strain, and strain rates at systole, early and late diastole were compared between the two patient groups using t-tests. The Pearson correlation coefficient (r) was used to investigate the association between cine MRI-derived indices and pulmonary capillary wedge pressure (PCWP). Multivariable linear and logistic regression models were applied to assess the ability of MRI-derived parameters to predict PCWP and postcapillary PH. Compared to 26 precapillary PH patients, the 28 postcapillary PH patients had lower peak late radial diastolic displacement (0.43 ± 0.19 cm vs. 0.64 ± 0.18 cm) and velocity (12.2 ± 5.8 mm/s vs. 18.9 ± 5.6 mm/s) and peak late radial (52.1 ± 32.7%/s vs. 97.1 ± 38%/s) and circumferential (38 ± 19.8%/s vs. 63.1 ± 22.9%/s) strain rates. PCWP was correlated with peak late radial diastolic displacement (r=-0.54) and velocity (r=-0.57) and peak late radial (r=-0.63) and circumferential diastolic (r=-0.63) strain rates. Peak late radial strain rate could predict PCWP (β=-0.09) and postcapillary PH (β=-0.036). All p < 0.05. Cine MRI-derived LV late diastolic motion/deformation properties can be used to estimate elevated left heart pressure in PH. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 1.

Changes in left ventricular size, geometry, pump function and left heart pressures during healthy aging.

There are cross-sectional and longitudinal imaging studies using echocardiography and cardiac magnetic resonance in healthy adult subjects which have demonstrated associations of left ventricular (LV) structure and pump function with age. There are also cross-sectional data regarding the relationships of age with invasively measured left heart chamber pressures. Increasing age is associated with decreases in LV end-diastolic volume (LVEDV), end-systolic volume (LVESV), end-diastolic length (LVEDL), stroke volume (SV) and cardiac output (CO), and increases in relative wall thickness (RWT), LV mass/LVEDV ratio (LVMVR) and ejection fraction (LVEF). Older age is not accompanied by a change in mean left atrial (LA) pressure, but there is both direct and indirect evidence which suggests that LV end-diastolic pressure (LVEDP) increases with age. LVEDV remains lower in older than younger subjects during fluid infusion and the resulting increases in LA pressure. The combination of an increase in LVEF with reductions of both SV and CO demonstrates an age-related increase in divergence between LVEF and LV pump function. A lower LVEDV in older compared to younger subjects can be characterized as an aging-related decrease in LV capacity, with the higher LVEDP in older subjects also indicating a reduction of preload reserve.

Pulmonary Hypertension Resolves Post Transplantation in Patients Treated with Milrinone or Dobutamine

Heart failure (HF) represents a significant cause of morbidity and mortality in the US. Heart transplantation can lead to significant long-term survival. One complication of HF is the presence of pulmonary hypertension (PH) secondary to increased left heart pressures. The presence of fixed PH is a contraindication to heart transplantation. Milrinone is hypothesized to lead to pulmonary vasodilation through its inhibition of PDE-4 and may be the better inotrope in patients with PH being evaluated for transplantation. In this study we investigate the effects of pre-transplant inotrope selection with milrinone or dobutamine on post-transplant pulmonary hemodynamics. Patients were selected from those receiving heart transplants at the Ohio State Wexner Medical Center between 1/1/2009-12/31/2018 with approval from the Ohio State University Biomedical Institutional Review Board. Patients were excluded if they had previous diagnoses of group 1 PH, CKD III, or prior heart transplant. Prior to transplant, pulmonary hemodynamic data assessed by right heart catheterization (RHC) were obtained before and during (7-365 days) milrinone or dobutamine therapy. Post-transplant RHC data were obtained one month and one year post transplant. We identified 22 patients treated with milrinone and 16 patients treated with dobutamine who met inclusion criteria for this study. Patients treated with milrinone had higher pre-inotrope mean pulmonary arterial pressure (mPAP; 38.6 vs. 27.5mmHg, p< 0.0001) and pulmonary vascular resistance (3.72 vs 2.24 woods units, p<0.01). After transplantation there was no difference in mPAP in patients treated with milrinone or dobutamine at one month (20.8 vs. 20.9 mmHg, p = 0.96) or one year (16.4 vs 16.0 mmHg, p=0.81) (Fig. 1). In patients who receive a heart transplant, PH resolves regardless of pre-transplant inotrope selection. The study was limited by its retrospective nature and small sample size. Future investigation is warranted.

A model based on clinical parameters to identify myocardial late gadolinium enhancement by magnetic resonance in patients with aortic stenosis: An observational study.

ObjectiveWith increasing age, the prevalence of aortic stenosis grows exponentially, increasing left heart pressures and potentially leading to myocardial hypertrophy, myocardial fibrosis and adverse outcomes. To identify patients who are at greatest risk, an outpatient model for risk stratification would be of value to better direct patient imaging, frequency of monitoring and expeditious management of aortic stenosis with possible earlier surgical intervention. In this study, a relatively simple model is proposed to identify myocardial fibrosis in patients with a diagnosis of moderate or severe aortic stenosis.DesignPatients with moderate to severe aortic stenosis were enrolled into the study; patient characteristics, blood work, medications as well as transthoracic echocardiography and cardiovascular magnetic resonance were used to determine potential identifiers of myocardial fibrosis.SettingThe Royal Brompton Hospital, London, UKParticipantsOne hundred and thirteen patients in derivation cohort and 26 patients in validation cohort.Main outcome measuresIdentification of myocardial fibrosis.ResultsThree blood biomarkers (serum platelets, serum urea, N-terminal pro-B-type natriuretic peptide) and left ventricular ejection fraction were shown to be capable of identifying myocardial fibrosis. The model was validated in a separate cohort of 26 patients.ConclusionsAlthough further external validation of the model is necessary prior to its use in clinical practice, the proposed clinical model may direct patient care with respect to earlier magnetic resonance imagining, frequency of monitoring and may help in risk stratification for surgical intervention for myocardial fibrosis in patients with aortic stenosis.

Abstract 330: Intra-Arrest Cardioplegia Prevents the Diastolic Dysfunction Induced by Prolonged VF Arrest

Introduction: There are approximately 400,000 out-of-hospital cardiac arrests annually, including one-third with VT/VF as their initial rhythm. Approximately 60% of VF arrests are refractory to initial resuscitation requiring prolonged CPR and transport to an ECPR center where available. Limiting myocardial injury during this time is critical as it contributes CPR efficiency. The aim of this study was to investigate the effect of cardioplegia on preservation of cardiac function during cardiac arrest. Hypothesis: Following induction of VF, the administration of potassium-based cardioplegia will reduce energy utilization and prevent diastolic dysfunction with preservation of contractility following washout of cardioplegia. Methods: Hearts were isolated from male Brown Norway rats (n=8) and prepared on a Langendorff apparatus in Krebs solution. Left ventricular pressure was measured throughout the study. Hemodynamics were obtained for 15 min prior to 2 min of rapid pacing to induce VF. After 10 min of VF, cardioplegia was induced with a bolus of 160 μeq potassium. After 10 min, the potassium was washed out and the hearts were reperfused with Krebs-Henseleit solution. Hemodynamics were measured for another 60 min. Results: Baseline hemodynamics were similar between the control and cardioplegia groups. Cardioplegic hearts had significantly lower left heart pressures at the end of the VF time compared to control hearts (24 vs. 74 mmHg, p&lt;0.05). Following 60 min of reperfusion and cardioplegia washout, diastolic pressures remained lower in hearts receiving cardioplegia (39 vs 10 mmHg, p&lt;0.05). After 60 min of reperfusion, systolic pressures were the same among the groups, and while rate of contraction and relaxation were numerically faster in hearts receiving cardioplegia, these differences were not significant. Conclusions: Potassium cardioplegia, given during ongoing VF arrest, was effective at preventing diastolic dysfunction caused by prolonged ischemia. Washout of the cardioplegia at the time of reperfusion allowed for ROSC and preserved left ventricular relaxation. These studies suggest that the use of cardioplegia in refractory VT/VF arrest may be beneficial in reducing myocardial damage and preserving function during prolonged CPR.

Design and preliminary results of FRENSHOCK 2016: A prospective nationwide multicentre registry on cardiogenic shock

Most data on the epidemiology of cardiogenic shock (CS) have come from patients with acute myocardial infarction admitted to intensive cardiac care units (ICCUs). However, CS can have other aetiologies, and could be managed in intensive care units (ICUs), especially the most severe forms of CS. To gather data on the characteristics, management and outcomes of patients hospitalized in ICCUs and ICUs for CS, whatever the aetiology, in France in 2016. We included all adult patients with CS between April and October 2016 in metropolitan France. CS was defined (at admission or during hospitalization) by: low cardiac output, defined by systolic blood pressure<90mmHg and/or the need for amines to maintain systolic blood pressure>90mmHg and/or cardiac index<2.2L/min/m2; elevation of the left and/or right heart pressures, defined by clinical, radiological, biological, echocardiographic or invasive haemodynamic overload signs; and clinical and/or biological signs of malperfusion (lactate>2mmol/L, hepatic insufficiency, renal failure). Over a 6-month period, 772 patients were included in the survey (mean age 65.7±14.9 years; 71.5% men) from 49 participating centres (91.8% were public, and 77.8% of these were university hospitals). Ischaemic trigger was the most common cause (36.3%). To date, FRENSHOCK is the largest CS survey; it will provide a detailed and comprehensive global description of the spectrum and management of patients with CS in a high-income country.

Abstract P252: Stress Echocardiography in Assessment of Symptoms in Obese Patients

Introduction: Obesity and obesity related illness continues to be an epidemic in the United States and worldwide. Obesity carries substantial risk of cardiovascular disease (CVD), and symptoms (shortness of breath, decreased exercise tolerance, etc) related to CVD can be nonspecific. Stress testing may identify the cause of these symptoms in obese patients (body mass index (BMI) &gt; 30.) Stress echocardiography has evolved to be capable of comprehensive hemodynamic assessment as well as functional and myocardial perfusion analysis and may be ideal for symptom evaluation in the obese. Methods: 1,615 consecutive patients (52% women, age 61±41 yrs, BMI 28±6) underwent stress perfusion ECHO (treadmill in 913, supine bike in 623 and dobutamine in 79 patients) between 2012 and 2014. Imaging included contrast/perfusion imaging and multi-method assessment of regional and global left and right heart systolic and diastolic function, left ventricular (LV) volumes, quantitative valve function, left and right heart pressures, peak/mean pulmonary artery pressures, pulmonary vascular resistance, and LV mass. Standard statistical methods were used. Results: Of the 1,615 patients analyzed, 516 (32%) were obese patients (BMI 36±5) and in the obese group females were 48% (vs 53% in non-obese). Both groups underwent similar stress modalities (58% vs 56% treadmill, 6% vs 4% dobutamine, and 36% vs 40% bike). Diabetes (21% vs 10%) and hypertension (57% vs 44%) were more common in obese (p&lt; 0.05). LV mass is disproportionately higher (113±30 vs 97±33 gm/M2) in obese patients (P&lt; 0.01). Additionally, obese patients had statistically significant findings (p&lt; 0.01) of LV hypertrophy (62% vs 26%), diastolic dysfunction (65% vs 44%), and at least moderate pulmonary hypertension (48% vs 34%). Overall, abnormal tests were more common in obese (83% vs 59%, p&lt;0.01). Multiple abnormalities were more common (p&lt;0.01): 1-3 abnormalities (13% vs 16%) and &gt; 4 abnormalities (70% vs 43%). Unexpectedly, the data showed no statistically significant difference between obese and non-obese in the incidence of ischemia (10% vs 11%), myocardial infarction (5% vs 4%), and cardiomyopathy (6% vs 5%). Conclusions: Comparative analysis of the data from stress ECHO revealed obese patients had disproportionally higher LV mass index/LV hypertrophy. Stress testing provoked worse diastolic dysfunction and much worse pulmonary vascular dysfunction in the obese patients. The triad of LV hypertrophy/diastolic dysfunction/pulmonary vascular disease with provoked moderate to severe pulmonary hypertension was the main cause of symptoms in obese patients. Hemodynamic stress ECHO is the ideal modality for evaluation of nonspecific symptoms of CVD in obese patients, as it can classify the cause of symptoms and the extent of pathology. Thereby, it may be the ideal test to guide treatment.

Early predictive factors of 30-days mortality in cardiogenic shock: An analysis of the FRENSHOCK multicenter prospective registry

Cardiogenic shock (CS) remains a severe but poorly understood pathology. Many predictive death scores have been previously described but have focused in ischemic CS and took into account data related to the management of these patients. So, there is an urgent need for simple and objective criteria to assess the short-term CS mortality regardless of the initial etiology. Methods FRENSHOCK registry (NCT02703038) was a large prospective multicenter registry of CS patients admitted in intensive cardiac and general critical care units between April and October 2016 in France. Patients were included if they met the following three criteria:. –low cardiac output defined by SBP < 90 mmHg and/or the need of amines, or a CI < 2.2L/min/m 2 (TTE or Swan-Ganz); –elevation of left and/or right heart pressures defined by clinic/radiology/biology/echocardiography/Swan-Ganz; –clinical and/or biological signs of hypoperfusion. We studied factors related to 30d mortality using Kaplan–Meier analyses and Cox proportional hazards modeling. 772 patients were included (male 72%, age median 66y). Non-ischemic CS were predominant (64%) although type 1 infarction was infrequent (17%). Mortality at 30–days was 26%. Non-survivors were older, had more previous renal failure, marbles, and atrial fibrillation at admission. They had lower SBP and DBP. Diagnostic tests revealed higher arterial lactate–CRP–natriuretic peptids–kaliemia; and lower pH - prothrombin time–haemoglobin–eGFR but also LVEF. Multivariate analysis retained age, low systolic blood pressure, high arterial lactate, low eGFR, low LVEF as significant predictors of 30–days mortality. Ischemic etiology or type 1 infarction were not predictive. Five simple, practical and easy to find signs were found significant predictors of short-term mortality and could be useful in providing a more accurate and stratified definition of CS's patients in order to tailor additional therapies.

Cardiogenic shock in France: What and who are we talking about? A descriptive analysis of the FRENSHOCK multicenter prospective registry

Epidemiologic data about cardiogenic shock (CS) are still poor and focused on ischemic CS, forgetting all part of the CS encountered in clinical practice. FRENSHOCK registry (NCT02703038) was a large prospective multicenter registry of non-selected CS patients admitted in critical care units realized between April and October 2016 in France. Patients were included if they met the following three criteria: – low cardiac output defined by SBP < 90 mmHg and/or the need of amines, or a low cardiac output defined by CI < 2.2L/min/m 2 (TTE or Swan–Ganz); – elevation of left and/or right heart pressures defined by clinic/radiology/biology/echocardiography/Swan-Ganz; – clinical and/or biological hypoperfusion. In total, 772 patients were included in 48 centers (male 72%, mean age of 66y). Comorbidities associated previous coronary revascularization 26%, peripheral arterial disease 15%, renal failure 21%, COPD 6%, diabetes 28%, tobacco 28%, dyslipidemia 35% and hypertension 47%. 56% were known for previous cardiomyopathy (30% ischemic, 10% idiopathic, 8% valvular). CS etiology often associated several triggers: ischemic was retained for 36% (type 1 infarction 17%). Non-ischemic trigger factors were predominant (64%): supra-ventricular (13%) and ventricular arrythmia (13%), infection (12%), iatrogenic (6%), conductive disorders (2%), non-observance (4%), and others (14%). At admission median SBP was 101.2 mmHg. Right heart failure signs were present in 49% and left signs in 72% (Killip IV 49%). Biological analysis found high lactate (3.0 mmol/L), renal (eGFR 49.6 ml/min) and hepatic alteration (ASAT 90.0 UI/ml; PT 57.1%). Median LVEF was 26.3% and TAPSE 13.4 mm. When realized (52%) coronarography was pathological in 81% (monotroncular 31%, bitroncular 35% and tritroncular 34%). A culprit lesion (79%) concern LVA 48%, RCA 23% and left main 15%. CS presentation and etiology are heterogeneous with a predominance of non-ischemic CS in practice.

Hemodynamic assessment of atrial septal defects.

Atrial septal defect (ASD) is one of the most common congenital cardiac anomalies. ASD can present as an isolated lesion in an otherwise normal heart or in association with other congenital heart conditions. Regardless of the type of ASD, the direction and degree of shunting across the communication is mainly determined by the difference in compliance between the right and left ventricle. Hemodynamics in children is characterized by left-to-right shunting, dilated right heart structures and normal pulmonary artery pressures (PAP). Patients diagnosed at adult age often present with complications related to long-standing volume overload such as pulmonary artery hypertension and right and left ventricular dysfunction. Diagnostic catheterization is usually not indicated unless there is suggestion of pulmonary hypertension on echocardiography. In older patients and/or in those with ventricular dysfunction, measurement of left heart pressures during temporary balloon occlusion is recommended prior to device closure as it may not be tolerated. In ASD associated with other congenital malformations, shunting degree and direction will depend upon underlying condition. Restrictive ASD can result in significant hemodynamic compromise in neonates with conditions such as hypoplastic left heart syndrome (HLHS) and transposition of the great arteries (TGA). In most cases, hemodynamics can be estimated with echocardiography only.

Pulmonary Vasoconstriction and Vascular Remodeling Play Role in Reactive Pulmonary Hypertension in Rats

IntroductionThe majority of clinical cases of pulmonary hypertension (PH) are caused by left heart failure. Some patients with venous PH induced by left heart pressure overload develop increase in resistance in the arterial part of the pulmonary circulation (reactive PH). We developed a new animal model of reactive PH caused by left heart pressure overload. We tested hypothesis that pulmonary arterial vasoconstriction and/or pulmonary vascular remodeling play role in our rodent model of reactive PH.MethodsLeft heart pressure overload was induced in adult male Wistar rats by partial intravascular obstruction of the ascending aorta. Three weeks later the experimental rats (group E, n=6) were compared to controls (group C, n=7). In isolated lungs perfused with salt solution with albumin we studied hemodynamic changes in pulmonary circulation by analysis of perfusion pressure increments induced by increasing perfusion flow (P/Q relationship). The P/Q relationship measurement was repeated after adding sodium nitroprusside into perfusate to reveal presence of pulmonary arterial vasoconstriction. In lung histology we counted remodeled peripheral pulmonary vessels in the group E compared to controls.ResultsThe slope of the P/Q relationship was significantly increased in the group E compared to controls (0.112±0.003 mmHg.mL−1.min−1 vs. 0.0046±0.002 mmHg.mL−1.min−1; p&lt;0.0001). Sodium nitroprusside did not alter the slope in controls (0.043±0.002 mmHg.mL−1.min−1). In the group E, sodium nitroprusside reduced the slope to a value not different from that in controls (0.044±0.001 mmHg.mL−1.min−1). In lung histology, 74 % of the small pulmonary vessels had muscularized media in the group E, compared to only 24 % in controls (p&lt;0.01).ConclusionPulmonary vasoconstriction and pulmonary vascular remodeling are involved in the new model of reactive pulmonary hypertension in rats.Support or Funding InformationGrants: GAUK 210216 and GACR 17‐11223SThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.