Decrease In End-diastolic Volume Research Articles

Comparative study of the effects of preferential left ventricular and biventricular pacing on echocardiographic and cardiorespiratory indices and clinical status of heart failure patients: preliminary

Abstract Introduction Nonresponse to cardiac resynchronization therapy (CRT) has been related with right ventricular dysfunction. Preferential left ventricular pacing (pLV-P) can achieve left ventricle resynchronization allowing for intrinsic activation of the right side, and benefit cardiac output while reducing atrial fibrillation occurrence. Moreover, the AdaptivCRT® algorithm also automatically adjusts interventricular (V-V) delay every minute. Methods We evaluated the effects of a pLVP algorithm on 100 systolic heart failure patients ( all Caucasians, 49% male; 67 +/- 8 years old; 51% ischemic cardiomyopathy; 44% diabetics; NYHA II-III) following randomization to standard biventricular pacing and pLVP, on echocardiographic and cardiopulmonary exercise test indices of functional status. Device programming was based on echocardiography-evaluated maximization of stroke volume and subsequent interventricular and atrioventricular delay adjustments delegated to the device. The follow-up consisted of 6 and 12-months visits; after the 1rst month of optimizing maximum CRT response. Results Significant comparative effects of pLV-P over optimized CRT were noted regarding right ventricle systolic velocity in TDI at 12-months from baseline (mean (SE); 4.5(0.8), p=0.035); decrease in end-diastolic volume of left ventricle (mean (SE); 11.33(7), p=0.035); decrease in right ventricle strain mean ((SE); 9.2(2.1), p=0.03). According to other echocardiographic indices, again taking into account baseline levels, patients in pLV-P group exhibited lower E/e value at 6-months (mean (SE); 8.390(4,3), p=0.04), and at 12 -months (mean (SE); 7.45(3.9), p=0.035); improved values in left atrium contractility strain at 12-months (mean (SE); 8.390(0.8), p=0.04); a borderline improvement in left ventricular ejection fraction (mean (SE); 8.7(433), p=0.05) at 12-months; and borderline improvement in left ventricular longitudinal strain at 6-months (mean (SE); 4.9(2.6), p=0.035), compared to optimized CRT. In CPET, taking into account baseline levels, patients in the pLVP group showed higher METs at 12-months (mean (SE); 1,16(0.8), p=0.03) compared to opt CRT group; higher predicted Ventilation rate (%) even from 6-months (mean (SE); 8.167(5,7), p=0.03) and higher predicted peak VO2 (%) at 6 months (mean (SE); 34,13(14), p=0.03) and borderline significance at 12 months (mean (SE); 4.88(3), p=0.08), compared to opt CRT. Conclusions In the preliminary findings of READAPT study, it seems that pLVP optimized by a standardized echocardiographic protocol in patients with preserved AV conduction and LBBB, can achieve improvement in parameters of right ventricular and left atrium structure and function, as well as in survival-predictive parameters of CPET compared to optimized CRT during the 12-months of follow-up.

LV reverse remodeling after SAVR in patients with severe symptomatic aortic stenosis: impact on the clinical outcome

Abstract Introduction Surgical aortic valve replacement (SAVR) is the treatment of choice for young patients with severe aortic stenosis (AS) and low surgical risk. Left ventricular (LV) reverse remodeling (RR) after surgery is expected to occur. However, this is not always the case following afterload relief, and this may impact the prognosis. We aimed to assess the prognostic effect of distinct definitions of LV RR after SAVR in the long-term outcome of patients with severe AS. Methods Single-centre prospective study including patients referred for SAVR due to severe symptomatic AS, with no previous history of ischemic cardiomyopathy. Both pre- and post-operative transthoracic echocardiographic (TTE) and cardiac magnetic resonance (CMR) study (at the 3rd to 6th month after SAVR) were performed. LV RR was defined when in presence of at least one of the imaging criteria: >15% decrease in end-diastolic volume (EDV) by CMR; >15% decrease in LV indexed mass (LVM) by CMR; >10% decrease in geometric remodeling (LV mass/EDV ratio) by CMR; >10% increase in LV ejection fraction (LVEF) by CMR; >50% increase on global longitudinal strain (GLS) by TTE. We assess the prognostic value of RR definitions for the outcome after SAVR using Cox regression and Kaplan-Meier analysis. The primary endpoint was defined as all-cause mortality, heart failure (HF) hospitalization or worsening HF. Results We enrolled 140 patients – mean age 71±9 years-old, 49% male, predominantly high-gradient-normal flow AS (mean gradient 65±18mmHg, aortic valve area 0.7±0.2cm2, index stroke volume 47±11mL/m2) submitted to SAVR. At a mean follow-up (FUP) of 34±12 months, 23 (16%) patients met the primary endpoint: 4% (5 patients) died immediately after surgery; three patients died at the FUP (overall mortality rate of 6%). 12 patients (9%) were admitted for HF and 7 (5%) had at least one episode of worsening HF. 118 patients had complete pre and post-surgery imaging study (mean FUP: 36±10 months): 103 patients (87%) had at least one RR parameter (Table 1). Post-operative RR was not independently associated with the clinical outcome (Figure 1A). LVM was the sole independent predictor of the outcome at univariate analysis (Figure 1B–F). Conclusions LV RR after SAVR is highly prevalent in a cohort of patients with classical severe symptomatic AS. However, only LVM regression independently predicts the clinical outcome after surgery. This may stand the greater importance of structural reverse remodeling, rather than LV functional improvement, after pressure overload relief.

Hemodynamics with mechanical circulatory support devices using a cardiogenic shock model

Mechanical circulatory support (MCS) devices, including veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and Impella, have been widely used for patients with cardiogenic shock (CS). However, hemodynamics with each device and combination therapy is not thoroughly understood. We aimed to elucidate the hemodynamics with MCS using a pulsatile flow model. Hemodynamics with Impella CP, VA-ECMO, and a combination of Impella CP and VA-ECMO were assessed based on the pressure and flow under support with each device and the pressure–volume loop of the ventricle model. The Impella CP device with CS status resulted in an increase in aortic pressure and a decrease in end-diastolic volume and end-diastolic pressure (EDP). VA-ECMO support resulted in increased afterload, leading to a significant increase in aortic pressure with an increase in end-systolic volume and EDP and decreasing venous reservoir pressure. The combination of Impella CP and VA-ECMO led to left ventricular unloading, regardless of increase in afterload. Hemodynamic support with Impella and VA-ECMO should be a promising combination for patients with severe CS.

A novel ultrasound-derived index of intra-myocardial work, utilizing automated AI segmentation, quantifies energy stored in systole and used for diastolic recoil during isovolumic relaxation

Abstract Introduction The commonly used Pressure-Volume loops focus on the cavity volume and quantify the cardiac systolic work. We focused on changes in wall geometry and have hypothesized that pressure-wall area relationships, in short-axis, relate to the intra-myocardial work (IMW) that is stored during systole and released during early diastole. Purpose The study aims to validate the novel IMW concept and to test its ability to quantify the severity of diastolic dysfunction in a model of myocardial injury during inflammation. Materials and Methods Short-axis ultrasound cines were continuously acquired (12MHz, 40-70 fps) in Langendorff perfused isolated rat hearts (N=7), with unique preload and afterload control of both ventricles. Dedicated artificial intelligence segmentation model was developed for fast and accurate quantification of both Pressure-Volume loops and IMWs. Inflammatory myocardial injury was emulated by adding MMP8 (secreted by activated macrophages and neutrophils) to the perfusion. Results 120,000 echocardiographic images of isolated rat hearts (n=7) were analyzed. The wall dynamics generated counterclockwise loops on the pressure-wall area plane that consisted of three phases: (1) Initial fast and large wall thickening, with 74±15% of the total wall area increase and only 7.79±6.44% of the total systolic pressure development. (2) The main (94.71±8.01%) systolic pressure upstroke, with only minor further changes in wall area. (3) Closure of the IMW loop during the diastolic isovolumic relaxation. This phase describes the fast energy release, when moving over the hypotenuse of the triangle-like loop, from end-systole to the end of the isovolumic relaxation. The IWM generated during the two systolic phases and released during diastole was of the same order as the systolic external work. MMP perfusion led to progressive shift of the end-diastolic pressure cavity-volume relationship to lower volumes, with marked decrease in end-diastolic volume (-20.0±17.2%, p=0.04) at the same filling pressure. There were insignificant changes in the systolic maximal elastance, hence, the progressive decline in myocardial recoil was associated with decrease in the external work. In parallel, there was conspicuous drop in the IMW (-60.82±19.44%, p=0.03). While the e` tracks the motion of a single point on the mitral annulus, the suggested IWM is based on monitoring a large myocardial mass and is easier to be acquired. The major fast changes in the IMW loops occurred at the isovolumic contraction and relaxation phases, and they relate to myocardial twist and recoil and to fast changes in myocardial shape. Conclusions The novel IMW is easily derived from short-axis echocardiographic images, and describes the systolic-to-diastolic energy conversion. The matrix plays a key role as the main energy storage element for myocardial recoil. IMW may play important roles in cardiac recoil and in assessment of diastolic dysfunction.Intra-myocardial work - MMP8 perfusion

Transapical ventricular reshaping reduces functional mitral regurgitation and improves ventricular function in a preclinical model of ischemic cardiomyopathy

ObjectiveA significant proportion of patients with advanced heart failure present with dilated left ventricles and functional mitral regurgitation. These patients currently have limited treatment options. The MitraClip device (Abbott) has benefited only patients with smaller left ventricles (end-diastolic dimension <70 mm), whereas those with larger left ventricles did not benefit. A possible explanation is correcting functional mitral regurgitation alone may not adequately reduce the wall stresses of a dilated left ventricle. We have developed a beating-heart device that not only approximates the papillary muscles to reduce functional mitral regurgitation but also modifies the left ventricle size and shape to reduce wall stress. MethodsYorkshire swine (n = 16) had a myocardial infarction induced by permanent occlusion of the left circumflex with intracoronary ethanol. Three months later, the animals developed heart failure and moderate or greater functional mitral regurgitation. Through a transapical approach, the new device was implanted under echocardiography guidance to reshape the left ventricle and correct functional mitral regurgitation. The acute impact of this approach on the mitral valve and left ventricle was assessed with echocardiography and invasive hemodynamics. ResultsAfter reshaping, echocardiography showed a decrease in end-diastolic volume by 36.3 ± 30.5 mL (P < .001), a decrease in sphericity index by 0.143 ± 0.087 (P < .001), and an increase in ejection fraction of 5.90% ± 6.38% (P < .01). Mitral valve tenting area was reduced by 39.29 ± 33.66 mm2 (P < .001), coaptation length was increased by 2.12 ± 1.02 mm (P < .001), and posterior excursion angle was improved by 9.07° ± 9.14° (P < .01), resulting in functional mitral regurgitation reduction. ConclusionsCorrection of functional mitral regurgitation with favorable changes in mitral valve geometry and reduction in left ventricle geometry is possible with the proposed device.

Left ventricular remodeling in normotensive Wistar rats exposed to intermittent hypoxia of different duration

Intermittent hypoxia has been studied for many years as a promising non-pharmacological method of cardiovascular disease prevention. Hypoxic effects are accompanied by structural and functional changes in the myocardium. There is a direct link between the duration of hypoxic exposures and the severity of left ventricular myocardial remodeling. A range of histochemical markers of myocardial remodeling (cardiotrophin-1, titin, collagen type 1, annexin V) characterizing parenchymal-stromal relationships in the myocardium has shown high informativeness and prognostic value. The aim of the study was to examine cardiotrophin-1, titin, collagen type 1, annexin V and the morphofunctional state of the left ventricle of the heart in experimental rats exposed to intermittent 15-day (IH15) and 60-day hypoxia (IH60). Materials and methods. Intermittent hypoxia was modeled using 30 normotensive male Wistar rats, 7–8 months old, which were randomly assigned to 3 experimental groups of 10 animals each: 1) INT – a control group – intact animals (196.3 ± 6.8 g); 2) IH15 – 15-day hypoxia (205.6 ± 4.1 g); 3) IH60 – 60-day hypoxia (201.1 ± 5.5 g). The study compared the effects of intermittent hypoxia of varying duration: 15-day and 60-day hypoxia. Experimental modeling of intermittent hypoxia of 2 terms revealed a number of differences between the effects dependent on this factor duration through functional (blood pressure measurement, echocardiography) and immunofluorescent studies. Results. Blood pressure in rats of both groups was in the normotensive range, but an increase in systolic by 10 % and diastolic by 19 % was found in IH60 group compared to IH15 group (p &lt; 0.05). In IH15 group, there was a significant decrease in end-diastolic dimension by 20 %, end-systolic dimension by 22 %, an increase in the thickness of left ventricular posterior wall by 44 % and interventricular septum by 33 % as well as left ventricular mass by 12 %, indicating concentric remodeling of the left ventricle, the development of which was confirmed by a 76 % increase in relative wall thickness compared to that in the control group (p &lt; 0.05). Along with these changes, a decrease in end-diastolic volume by 47 %, end-systolic volume by 48 %, stroke volume by 49 % and cardiac output by 50 % with preserved ejection fraction was revealed (p &lt; 0.05). While the parameters of IH60 rats were characterized by an increase in the thickness of interventricular septum by 33 % and left ventricular posterior wall by 17 %, as well as left ventricle mass by 23 %, relative left ventricular wall thickness was 15 % higher than the control value (p &lt; 0.05). At the same time, diastolic volume was 9 % decreased and systolic volume was 24 % increased (p &lt; 0.05). Also, cardiac output was increased by 58 % compared to that in 15-day hypoxic rats with an 8 % decrease in ejection fraction (p &lt; 0.05). The concentrations of markers in IH60 group exceeded those in IH15, namely: cardiotrophin-1 by 39 %, titin by 70 %, collagen type 1 by 60 % and annexin V by 130 % (p &lt; 0.05). Conclusions. 15-day hypoxia forms concentric left ventricular hypertrophy according to echocardiography findings; the study of marker profile of myocardial remodeling has revealed the development of moderate hypertrophy with increased resilient-elastic properties and decreased intensity of cardiomyocyte death. Remodeling caused by 60-day hypoxia is characterized by the eccentric pattern of changes with severe hypertrophy, significant fibrosis associated with apoptosis of cardiomyocytes. Such morphofunctional state of the myocardium may indicate the initial stages of maladaptation, increasing the risk of heart failure development.

Discordance between 2D and 4D flow in the assessment of pulmonary regurgitation severity: a right ventricular remodeling follow-up study.

Pulmonary regurgitation (PR) is common in adult congenital heart disease (ACHD). 2D phase contrast MRI is the reference method for the quantification of PR and helps in the decision of pulmonary valve replacement (PVR). 4D flow MRI can be an alternative method to estimate PR but more validation is still needed. Our purpose was to compare 2D and 4D flow in PR quantification using the degree of right ventricular remodeling after PVR as the reference standard. In 30 adult patients with a pulmonary valve disease recruited between 2015 and 2018, PR was assessed using both 2D and 4D flow. Based on the clinical standard of care, 22 underwent PVR. The pre PVR estimate of PR was compared using the post-operative decrease in right ventricle end-diastolic volume on follow-up exam as reference. In the overall cohort, regurgitant volume (Rvol) and regurgitant fraction (RF) of PR measured by 2D and 4D flow were well correlated but with moderate agreement in the overall cohort (r = 0.90, mean diff. -14 ± 12.5mL; and r = 0.72, mean diff. -15 ± 13%; all p < 0.0001). Correlations between Rvol estimates and right ventricle end-diastolic volume decrease after PVR was higher with 4D flow (r = 0.80, p < 0.0001) than with 2D flow (r = 0.72, p < 0.0001). In ACHD, PR quantification from 4D flow better predicts post-PVR right ventricle remodeling than that from 2D flow. Further studies are needed to evaluate the added value of this 4D flow quantification for guiding replacement decision. • Using 4D flow MRI allows a better quantification of pulmonary regurgitation in adult congenital heart disease than 2D flow when taking right ventricle remodeling after pulmonary valve replacement as a reference. • A plane positioned perpendicular to the ejected flow volume as allowed by 4D flow provides better results to estimate pulmonary regurgitation.

Pulmonary congestion during Exercise stress Echocardiography in Hypertrophic Cardiomyopathy

BackgroundB-lines detected by lung ultrasound (LUS) during exercise stress echocardiography (ESE), indicating pulmonary congestion, have not been systematically evaluated in patients with hypertrophic cardiomyopathy (HCM).AimTo assess the clinical, anatomical and functional correlates of pulmonary congestion elicited by exercise in HCM.MethodsWe enrolled 128 HCM patients (age 52 ± 15 years, 72 males) consecutively referred for ESE (treadmill in 46, bicycle in 82 patients) in 10 quality-controlled centers from 7 countries (Belgium, Brazil, Bulgaria, Hungary, Italy, Serbia, Spain). ESE assessment at rest and peak stress included: mitral regurgitation (MR, score from 0 to 3); E/e’; systolic pulmonary arterial pressure (SPAP) and end-diastolic volume (EDV). Change from rest to stress was calculated for each variable. Reduced preload reserve was defined by a decrease in EDV during exercise. B-lines at rest and at peak exercise were assessed by lung ultrasound with the 4-site simplified scan. B-lines positivity was considered if the sum of detected B-lines was ≥ 2.ResultsLUS was feasible in all subjects. B-lines were present in 13 patients at rest and in 38 during stress (10 vs 30%, p < 0.0001). When compared to patients without stress B-lines (n = 90), patients with B-lines (n = 38) had higher resting E/e’ (14 ± 6 vs. 11 ± 4, p = 0.016) and SPAP (33 ± 10 vs. 27 ± 7 mm Hg p = 0.002). At peak exercise, patients with B-lines had higher peak E/e’ (17 ± 6 vs. 13 ± 5 p = 0.003) and stress SPAP (55 ± 18 vs. 40 ± 12 mm Hg p < 0.0001), reduced preload reserve (68 vs. 30%, p = 0.001) and an increase in MR (42 vs. 17%, p = 0.013) compared to patients without congestion. Among baseline parameters, the number of B-lines and SPAP were the only independent predictors of exercise pulmonary congestion.ConclusionsTwo-thirds of HCM patients who develop pulmonary congestion on exercise had no evidence of B-lines at rest. Diastolic impairment and mitral regurgitation were key determinants of pulmonary congestion during ESE. These findings underscore the importance of evaluating hemodynamic stability by physiological stress in HCM, particularly in the presence of unexplained symptoms and functional limitation.

In vitro benchtop mock circulatory loop for heart failure with preserved ejection fraction emulation.

In this work, a novel mock circulatory loop (MCL) is presented that is capable of simulating both healthy cardiac function and Heart Failure with preserved Ejection Fraction (HFpEF). This MCL differs from others presented in the literature as it features two independently actuated heart chambers, representing the left atrium and the left ventricle. This is an important improvement over other designs as it allows for potential HFpEF treatments to be examined, not just in relation to their effect on the left ventricle but also on the left atrium. The aim of this work was to show that novel MCL designs could be developed to allow for testing of new mechanical circulatory support devices for the treatment of HFpEF. Two loop configurations are presented, one featuring hard PVC cylindrical chambers and one that features soft silicone chambers which are anatomically analogous to the native heart. We show that both MCLs are capable of simulating the onset of HFpEF with a sustained increase in diastolic pressure of 62.03% and a sustained decrease in end diastolic volume (EDV) of 14.24%.

Exosomal microRNAs miR-30d-5p and miR-126a-5p Are Associated with Heart Failure with Preserved Ejection Fraction in STZ-Induced Type 1 Diabetic Rats.

Exosomal microRNAs (EXO-miRNAs) are promising non-invasive diagnostic biomarkers for cardiovascular disease. Heart failure with preserved ejection fraction (HFpEF) is a poorly understood cardiovascular complication of diabetes mellitus (DM). Little is known about whether EXO-miRNAs can be used as biomarkers for HFpEF in DM. We aimed to investigate the relationship between EXO-miRNAs and HFpEF in STZ-induced diabetic rats. We prepared STZ-induced diabetic rats exhibiting a type 1 DM phenotype with low body weight, hyperglycemia, hyperlipidemia and hypoinsulinemia. Histological sections confirmed atrophy and fibrosis of the heart, with collagen accumulation representing diabetic cardiomyopathy. Significant decreases in end-diastolic volume, stroke volume, stroke work, end-systolic elastance and cardiac output indicated impaired cardiac contractility, as well as mRNA conversion of two isoforms of myosin heavy chain (α-MHC and β-MHC) and increased atrial natriuretic factor (ANF) mRNA indicating heart failure, were consistent with the features of HFpEF. In diabetic HFpEF rats, we examined a selected panel of 12 circulating miRNAs associated with HF (miR-1-3p, miR-21-5p, miR-29a-5p, miR-30d-5p, miR-34a-5p, miR-126a-5p, miR-143-3p, miR-145-5p, miR-195-5p, miR-206-3p, miR-320-3p and miR-378-3p). Although they were all expressed at significantly lower levels in the heart compared to non-diabetic controls, only six miRNAs (miR-21-5p, miR-30d-5p, miR-126a-5p, miR-206-3p, miR-320-3p and miR-378-3p) were also reduced in exosomal content, while one miRNA (miR-34a-5p) was upregulated. Similarly, although all miRNAs were correlated with reduced cardiac output as a measure of cardiovascular performance, only three miRNAs (miR-30d-5p, miR-126a-5p and miR-378-3p) were correlated in exosomal content. We found that miR-30d-5p and miR-126a-5p remained consistently correlated with significant reductions in exosomal expression, cardiac expression and cardiac output. Our findings support their release from the heart and association with diabetic HFpEF. We propose that these two EXO-miRNAs may be important for the development of diagnostic tools for diabetic HFpEF.

Determination of the influence of risk factors for coronary artery disease on the effectiveness of cardiac surgery by the method of myocardial scintigraphy

Background. Myocardial revascularization is a life-saving technology that not only increases life expectancy, reduces recurrences of myocardial infarction and repeated surgery, but also improves its quality in patients with coronary artery disease. Risk assessment, the complexity of coronary artery disease, the presence of comorbidities, the area of hibernating myocardium, the patient’s consent are the basis for choosing a method of treatment. Positive structural and functional changes of the myocardium (increase in the area of viable myocardium), restoration or improvement of left ventricular systolic function (increase in ejection fraction and decrease in end-diastolic volume), reduction of angina are the expected result of the surgical treatment. Purpose – determining the influence of risk factors for coronary heart disease on the outcome of surgical treatment by aorto-coronary artery bypass grafting with the help of diagnostic evaluation of myocardial scintigraphy. Materials and Methods. To achieve the clinical tasks, 62 patients with coronary artery disease were examined. The mean age of the subjects was (59.6 ± 8.2) years. Myocardial scintigraphy was performed in SPECT with ECG synchronization (Gated SPECT). 99mTc-MIBI with an activity of 555–740 MBq was used. Myocardial scintigraphy was performed over time of treatment (before and after coronary artery bypass grafting) according to the protocol – One Day Rest. Results. The influence of risk factors was assessed using dynamic and static integrated indicators. The dynamic integral indicator did not show statistically significant risk factors: smoking (p = 0.54), left ventricular contractility (p = 0.43), the presence of myocardial infarction in past (p = 0.4), heart failure stage (p = 0.53) and functional class of angina (p = 0.08). The static integrated indicator also did not show statistically significant effects from smoking (p = 0.13), left ventricular contractility (p = 0.58), the presence of myocardial infarction in past (p = 0.1), heart failure stage (p = 0.11) and functional class of angina (p = 0.6). Conclusions. The risk factors for coronary artery disease, such as: myocardial infarction in past, left ventricular contractility, heart failure stage, functional class of angina and smoking, in the study group of patients, had no reported effect on revascularization by the method of aorto-coronary artery bypass grafting (static and dynamic integrated indicators p &gt; 0.05).

Role and place of radiotherapy in neoadjuvant treatment of pancreatic cancer

Background. Myocardial revascularization is a life-saving technology, which contributes to increase in lifespan, reduction in myocardial infarction recurrences and repeated surgeries along with improved life quality of the patients with coronary artery disease (CAD). Estimation of the risks, severity of coronary bed lesion, presence of concomitant diseases, and area of hibernating myocardium, as well as patient’s agreement are the basis of treatment method selection. Positive structural and functional changes in myocardium (increase in area of viable myocardium), restoration or improvement of systolic function of left ventricle (increase in ejection fraction and decrease in end-diastolic volume), reduction of angina symptoms are the expected results from the surgical treatment.&#x0D; Purpose – to determine the influence of risk factors for coronary artery disease on the outcome of surgical treatment by the method of aorto-coronary artery bypass grafting with the help of diagnostic evaluation of myocardial scintigraphy parameters.&#x0D; Materials and methods. For the implementation of the clinical objectives, 62 patients with coronary artery disease were examined. The average age of the patients was 59.6 ± 8.2 years. Myocardial scintigraphy was performed in the SPECT mode with ECG synchronization (Gated SPECT). 99mTc-MIBI with an activity of 555-740 MBq was used. Myocardial scintigraphy was conducted over time of treatment (before and after coronary artery bypass grafting) according to One Day Rest protocol.&#x0D; Results. The influence of risk factors was assessed using dynamic and static integral indices. The dynamic integral index didn’t reveal statistically significant risk factors: smoking (p = 0.54), left ventricular contractility impairment (p = 0.43), history of myocardial infarction (p = 0.4), stage of heart failure (p = 0.53), and functional class of angina (p = 0.08). The static integral index didn’t reveal statistically significant influence as well: smoking (p = 0.13), left ventricular contractility impairment (p = 0.58), history of myocardial infarction (p = 0.1), stage of heart failure (p = 0.11), and functional class of angina (p = 0.6).&#x0D; Conclusions. The studied risk factors for coronary artery disease, namely: history of myocardial infarction, left ventricular contractility impairment, stage of heart failure, functional class of angina, and smoking in the study group of patients had no registered influence on the revascularization effect by coronary artery bypass grafting method (integrated static and dynamic indices p &gt; 0.05).

Abstract 14327: Intramyocardial Delivery of an Imageable Theranostic Hydrogel Post Myocardial Infarction Alters Regional Strain and Reduces Remodeling in Chronic Porcine Model

Introduction: Myocardial infarction (MI) causes acute regional changes in stiffness and strain, resulting in pathological remodeling in the left ventricle (LV). Intramyocardial injection of hydrogel (HG) into the MI region may alter deformation and improve LV remodeling. Using high resolution cineCT (CCT) we evaluated changes in regional strain, global function, and geometry in chronic porcine MI model. Methods: Yorkshire pigs (n=12) subjected to 90 min balloon occlusion and reperfusion were randomized 5 days post MI to intramyocardial delivery of MI+HG (n=6) or MI only (n=6). Imageable HG was delivered in a 3x3 grid after assessing MI region with hybrid 201 Tl SPECT/CT. Contrast CCT was performed at baseline, day 5 (post MI before HG delivery), and day 12 (7 days post HG delivery) to assess end diastolic volume (EDV) and ejection fraction (EF). Custom software was used to calculate 3D myocardial Lagrangian strains on 6 HG animals and 3 MI only animals in remote, border (&gt;50% normal) and MI regions (&lt;50% normal). Results: At day 5 in both groups, EDV increased by 13.2% (p=0.016), LVEF decreased by 15.7% (p=0.008), and radial strain (E rr ) decreased in MI region by -0.11 (p=0.007). On day 12, EDV decreased by 8.3% in the MI+HG group but increased by 10.4% in the MI only group (p=0.003). LVEF increased significantly in the MI+HG group by 8.96% and was significantly greater than in MI only group (p=0.027) which had no significant changes. Average change in E rr between baseline and day 12 was not different between groups within the MI (p=0.13) or border region (p=0.67). However, average E rr did not decline in the MI+HG group (+0.029) but significantly declined in MI only group (-0.14, p=0.017) (MI+HG vs MI only; p=0.003), mirroring EDV changes. Conclusions: Intramyocardial delivery of HG 5 days post-MI resulted in greater improvement in E rr in remote region and global LVEF and a decrease in EDV suggesting reduced LV remodeling compared to MI only controls.

Peripartum Cardiomyopathy. Medical Support Strategy

Peripartum cardiomyopathy (PPCM) is an idiopathic myocardial insufficiency that occurs in the absence of any diagnosed heart disease during the last month of pregnancy or during the first 5 months after delivery.&#x0D; The aim. To improve immediate and long-term maternal outcomes in patients with PPCM by establishing an optimal strategy for its diagnosis, treatment, delivery and medical support during the postpartum period.&#x0D; Materials and methods. The article presents the experience of multidisciplinary medical care for 11 pregnant wo-men and postpartum women with dilated cardiomyopathy (DCM) on the basis of the National Amosov Institute of Cardio-vascular Surgery and the Institute of Pediatrics, Obstetrics and Gynecology named after acad. O. M. Lukianova of NAMS of Ukraine. After the differential diagnosis, 8 women were defined as patients with PPCM, and 3 women had family history of the disease (DCM in relatives). All the patients were examined according to the protocol using the history, examination, and instrumental and laboratory findings.&#x0D; Results. After in-hospital treatment there was an increase in the left ventricular ejection fraction (LVEF) in the group of patients with PPCM from 28.3 ± 9.3% to 37.6 ± 7.6% and a decrease in end-diastolic volume (EDV) from 196.7 ± 47.7 ml to 181.3 ± 59.7 ml, end-systolic volume (ESV) from 104.25 ± 33.3 ml to 94.2 ± 35.1 ml. In four cases, patients with severe left ventricular (LV) dysfunction underwent urgent preterm Cesarean section in the second trimester of pregnancy. There were no early maternal losses, there were two perinatal losses of extremely premature infants (16 and 27 weeks of gesta-tion). In the follow-up period (23.5 ± 11.6 months), LVEF further increased up to 42.9 ± 8.4% and EDV and ESV decreased up to 170.1 ± 49.5 and 82.7 ± 40.6 ml, respectively. In 7 (87.5%) patients with PPCM, a significant improvement in clini-cal condition and pumping function of the heart was registered at the time of discharge from the hospital, and there was further improvement in the indicators for another 12 months, but complete recovery of cardiac function was achieved only in 3 (37.5%) patients. In patients from the group of family type DCM, complete recovery of LV myocardial function was not observed in any of the 3 studied cases.&#x0D; The article discusses the timing of the occurrence and diagnosis of PPCM, the main clinical, instrumental and labora-tory signs of the pathology, methods of cardiological, cardiosurgical and obstetric support of such pregnant women.&#x0D; Conclusions. The terms of the onset of PPCM manifestations may be wider (earlier) according to our observations and should be the subject of further research. The strategy of medical care for pregnant women doesn’t particularly depend on the type of DCM. However, obstetric tactics aimed at early delivery of a patient with PPCM with severe myocardial insufficiency are feasible in combination with interruption of lactation and in most cases allow to achieve compensation of circulation and partial recovery of LV function. Prescription of bromocriptine for this purpose seems appropriate. The use of repeated courses of levosimendan in patients with PPCM is feasible and helps to improve the LV function in the early postpartum period.

Abstract 068: Hypertension And Longitudinal Changes In Cardiac Structure And Function In The Hispanic Community Health Study/Study Of Latinos: Echocardiographic Study Of Latinos (Echo-SOL) Ancillary Study

Introduction: Hypertension, one of the most modifiable risk factors of heart disease, induces cardiac remodeling and worsens myocardial function prior to the development of clinical symptoms. Using a comprehensive cohort of Hispanic/Latino adults, we assessed cardiac structure and function, in relation to hypertension, and the longitudinal impact of blood pressure control. Hypothesis: If baseline hypertensive adults are stratified by longitudinal blood pressure (BP) control, there will be differences in the progression of cardiac structure and function parameters. Methods: The Echo-SOL Ancillary Study provided serial comprehensive echocardiographic assessments of Hispanic adults aged 45-74 years. They were arranged into two groups based on the presence of baseline hypertension (&gt;140/90mmHg). Linear regression models were used to estimate the association between baseline BP properties and the longitudinal change in echocardiogram parameters. We then subdivided each group based on whether the they maintained BP control (&lt;140/90mmHg) on follow up and used linear regression models to test for significance among the mean longitudinal change of echocardiogram parameters. All analyses accounted for the complex sampling design of HCHS/SOL and Echo-SOL. Results: There was a total of 1818 adults at baseline, with 1643 obtaining serial echocardiograms an average of 4.3 years later, mean age of approximately 56 years. Among all adults, baseline pulse pressure was significantly associated with a longitudinal increase in left ventricular (LV) end diastolic volume (β=0.13, p=0.02), whereas the change in LV mass index longitudinally decreased with baseline diastolic BP (β=-0.14, p&lt;0.01). When isolating the subgroup defined as hypertensive at baseline, the adults who had uncontrolled BP on follow up had a greater absolute increase in the average E/E’ ratio and greater decrease in average E’ velocity, 0.95±0.08 and -0.96±0.06 respectively, compared to the adults with controlled BP 0.04±0.07 and -0.74± 0.04 respectively (p&lt;0.01). In addition, the controlled BP group had a greater absolute reduction in LV end-diastolic volume of 6.94mL than those with uncontrolled BP, 4.60mL (p&lt;0.01). Conclusions: Our study is the first to study the association of longitudinal impact of blood pressure control with cardiac structure and function in Hispanic/Latino adults. We found that higher baseline brachial BP properties were associated with reduced in LV mass index and increased LV end diastolic volumes. Among the baseline hypertensive adults, there was a significantly higher progression in diastolic dysfunction among the participants who had poor BP control, but those with controlled BP on follow up had greater LV enlargement. Despite these differences, both subgroups ultimately showed a collective progression in diastolic dysfunction and a decrease in end-diastolic volume over time.

Acute Unloading Effects of Sildenafil Enhance Right Ventricular–Pulmonary Artery Coupling in Heart Failure

BackgroundPhosphodiesterase-5A inhibitors (PDE5i) are sometimes used in patients with advanced heart failure with reduced ejection fraction before heart transplant or left ventricular assist device implantation to decrease right ventricular (RV) afterload and mitigate the risk of right heart failure. Conflicting evidence exists regarding the impact of these drugs on RV contractility. The aim of this study was to explore the acute effects of PDE5i on ventricular–vascular coupling and load-independent RV contractility. MethodsTwenty-two patients underwent right heart catheterization and gated equilibrium blood pool single photon emission computed tomography, before and after 20 mg intravenous sildenafil. Single photon emission computed tomography and right heart catheterization-derived data were used to calculate RV loading and contractility. ResultsPDE5i induced a decrease in the right atrial pressure (–43%), pulmonary artery (PA) mean pressure (–26%), and PA wedge pressure (PAWP; –23%), with favorable reductions in pulmonary vascular resistance (–41%) and PA elastance (–40%), and increased cardiac output (+13%) (all P < 0.01). The RV ejection fraction increased with sildenafil (+20%), with no change of RV contractility (P = 0.74), indicating that the improvement in the RV ejection fraction was related to enhanced RV–PA coupling (r = 0.59, P = 0.004) by a decrease in the ventricular load. RV diastolic compliance increased with sildenafil. The decrease in the PAWP correlated with RV end-diastolic volume decrease; no relationship was observed with the change in LV transmural pressure, suggesting decreased pericardial constraint. ConclusionsAcute PDE5i administration has profound RV afterload-reducing effects, improves the RVEF, decreases RV volumes, and decreases the PAWP, predominantly through relief of pericardial constraint, without effects on RV chamber contractility. These findings support further study of PDE5i in protection of RV function in advanced heart failure with reduced ejection fraction who are at risk of RV failure.

Effect of infarct stiffness on non-infarcted left and right ventricular tissue remodeling: a computational study based on myocardial mechano-transduction

Abstract Background/Introduction The mechanical properties of infarcted myocardium are important determinants of cardiac pump function and risk of developing heart failure following myocardial infarction (MI). Purpose To better understand the effects of infarct stiffness on compensatory hypertrophy and dilation of non-infarcted tissue in the left (LV) and right ventricle (RV), by using a computational model. Methods The CircAdapt computational model of the human heart and circulation was applied to simulate an acute MI involving 20% of LV wall mass. The simulation was validated using previously published experimental data. Subsequently, two degrees of increased infarct stiffness were simulated. In all three simulations, a model of structural myocardial adaptation of the non-infarcted tissue was applied, based on sensing of mechanical loading of myocytes and extracellular matrix (ECM). Results Mild and severe stiffening of the infarct reduced the increase of LV end-diastolic volume (EDV) from +23 mL to +17 mL and +16 mL, respectively, and the increase of LV non-infarcted tissue mass from +31% to +21% and +18%. RV EDV decreased after adaptation, and mild and severe infarct stiffening reduced the decrease of RV EDV from −21 mL to −12 mL and −10 mL, respectively. Increase of RV tissue mass was reduced from +13% to +8% and +7% with mild and severe infarct stiffening. In the LV, reduced dilation and hypertrophy were driven mainly by a reduction of maximum stress in the ECM and a higher stress between the myocytes and ECM following infarct stiffening. The decreased RV hypertrophy, but not EDV reduction, was caused by a reduction of maximum RV ECM stress and maximum RV active myofiber stress. Conclusions Model simulations predicted that a stiffened LV infarct reduces both LV and RV non-infarcted tissue hypertrophy as well as LV dilation. In LV remodeling, maximum ECM stress and stress between myocyte and ECM played a more prominent role than in RV remodeling, while maximum active stress was more important in the RV. Overview of all model simulations Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This work was funded by the Netherlands Organisation for Scientific Research and the Dutch Heart Foundation.

Feasibility of real-time cardiac MRI in mice using tiny golden angle radial sparse.

Cardiovascular magnetic resonance imaging has proven valuable for the assessment of structural and functional cardiac abnormalities. Even although it is an established imaging method in small animals, the long acquisition times of gated or self-gated techniques still limit its widespread application. In this study, the application of tiny golden angle radial sparse MRI (tyGRASP) for real-time cardiac imaging was tested in 12 constitutive nexilin (Nexn) knock-out (KO) mice, both heterozygous (Het, N = 6) and wild-type (WT, N = 6), and the resulting functional parameters were compared with a well-established self-gating approach. Real-time images were reconstructed for different temporal resolutions of between 16.8 and 79.8 ms per image. The suggested approach was additionally tested for dobutamine stress and qualitative first-pass perfusion imaging. Measurements were repeated twice within 2 weeks for reproducibility assessment. In direct comparison with the high-quality, self-gated technique, the real-time approach did not show any significant differences in global function parameters for acquisition times below 50 ms (rest) and 31.5 ms (stress). Compared with WT, the end-diastolic volume (EDV) and end-systolic volume (ESV) were markedly higher (P < 0.05) and the ejection fraction (EF) was significantly lower in the Het Nexn-KO mice at rest (P < 0.001). For the stress investigation, a clear decrease of EDV and ESV, and an increase in EF, but maintained stroke volume, could be observed in both groups. Combined with ECG-triggering, tyGRASP provided first-pass perfusion data with a temporal resolution of one image per heartbeat, allowing the quantitative assessment of upslope curves in the blood-pool and myocardium. Excellent inter-study reproducibility was achieved in all the functional parameters. The tyGRASP is a valuable real-time MRI technique for mice, which significantly reduces the scan time in preclinical cardiac functional imaging, providing sufficient image quality for deriving accurate functional parameters, and has the potential to investigate real-time and beat-to-beat changes.

Cardiac remodeling after large ST-elevation myocardial infarction in the current therapeutic era

The evolution and clinical impact of cardiac remodeling after large ST-elevation myocardial infarction (STEMI) is not well delineated in the current therapeutic era. The PRESERVATION I trial longitudinally assessed cardiac structure and function in STEMI patients receiving primary percutaneous coronary intervention (PCI). Echocardiograms were performed immediately post-PCI and at 1, 3, 6 and 12 months after STEMI. The extent of cardiac remodeling was assessed in patients with ejection fraction (EF) ≤ 40% after PCI. Patients were stratified by the presence or absence of reverse remodeling, defined as an increase in end-diastolic volume (EDV) of ≤10 mL or decrease in EDV at 1 month, and evaluated for an association with adverse events at 1 year. Of the 303 patients with large STEMI enrolled in PRESERVATION I, 225 (74%) had at least moderately reduced systolic function (mean EF 32 ± 5%) immediately after primary PCI. In the following year, there were significant increases in EF and LV volumes, with the greatest magnitude of change occurring in the first month. At 1 month, 104 patients (46%) demonstrated reverse remodeling, which was associated with a significantly lower rate of death, recurrent myocardial infarction and repeat cardiovascular hospitalization at 1 year (HR 0.44; 95% CI: 0.19-0.99). Reduced EF after large STEMI and primary PCI is common in the current therapeutic era. The first month following primary reperfusion is a critical period during which the greatest degree of cardiac remodeling occurs. Patients demonstrating early reverse remodeling have a significantly lower rate of adverse events in the year after STEMI.

P586Left ventricular volume and mass adaptation after 58-days head-down bed-rest assessed by cine-MRI, and effectiveness of high-intensity jump training countermeasure

Abstract Aims Prolonged immobilization generates cardiac deconditioning, a risk factor for cardiovascular disease, and efficient countermeasures (CM) are needed to prevent it. Our aim was to assess by Cine-MRI the effects of long-term strict head-down (−6 degrees) bed-rest (BR) deconditioning, and the effectiveness of high-intensity jump training CM, on left ventricular (LV) function and mass. Methods 23 male participants (29±6 years, 181±6 cm, 77±7 kg) were enrolled. The experiment was conducted at: envihab (Koln, DLR, Germany) as part of the European Space Agency BR studies. Volunteers were randomly allocated to the jump training group (JUMP, n=12) or the control group (CTRL, n=11). A typical training session consisted of 4x10 countermovement jumps and 2x10 hops in a sledge jump system, with 5–6 sessions per week. Steady-state free precession cine-MRI images were obtained (25 frames/cardiac cycle, 8mm thickness, no gap, no overlap) as stack of short-axis images covering the whole LV from base to apex, before (PRE) and after 58-days (HDT58) of BR. Endocardial and epicardial semi-automated contouring was performed using custom software. Results In CTRL group, at HDT58 a reduction in LV mass (9%), end-diastolic (21%), end-systolic (8%) and stroke volume (23%) were observed, while ejection fraction did not change. In JUMP group, the reduction in LV end-diastolic volume was only by 9%, followed by a decrease in end-systolic (10%) and stroke volume (10%), with a preservation of LV mass. In both groups, ejection fraction did not change. Left ventricular changes after 58d BR EDV (ml) ESV (ml) SV (ml) EF (%) Mass (g) CTRL PRE 171 (163; 191) 60 (58; 65) 113 (102; 124) 64 (63; 67) 133 (121; 160) HDT58 143 (131; 149)* 56 (50; 58)* 86 (83; 92)* 62 (60; 63)* 127 (106; 138)* JUMP PRE 156 (140; 204) 70 (61; 84) 91 (78; 117) 58 (56; 60) 118 (104; 134) HDT58 141 (135; 175)* 63 (54; 69)* 90 (78; 92)* 58 (55; 60) 113 (105; 128) Results expressed as median (25th; 75th percentiles). *p&lt;0.05 Wilcoxon non parametric paired test (PRE vs HDT58). CTRL: control group; JUMP: countermeasure group. Conclusions Cardiac adaptation to deconditioning due to immobilization induced by BR resulted in a reduction of cardiac volumes and function, together with a decrease in LV mass. Interestingly, the applied JUMP countermeasure appeared able to partially reverse these effects, in particular by reducing the decrease in end-diastolic volume and preserving LV mass. This information could be useful for better understanding physiologic changes in patients undergoing long periods of immobilization, as well as to apply the studied countermeasure during space flight to reduce cardiac deconditioning. Acknowledgement/Funding Italian Space Agency (contract 2018-7-U.0),CNES/DAR 48ehz747.01950965,BELSPO, via the European Space Agency PRODEX program (PEA 4000110826)