Reduced Left Ventricle Ejection Fraction Research Articles

Aging exacerbates cardiac dysfunction and mortality in sepsis through enhancing TLR2 activity.

Sepsis is prevalent in the elderly population with increased incidence and mortality. Currently, the mechanism by which aging increases the susceptibility to sepsis and worsens outcome is unclear. We tested the hypothesis that aging exacerbates cardiac dysfunction in sepsis through a Toll-like receptor 2 (TLR2)-dependent mechanism. Male young adult (4-6 months) and old (18-20 months) wild type (WT) and TLR2 knockout (KO) mice were subject to moderate sepsis by cecal ligation and puncture. Additional groups of young adult and old WT mice were treated with TLR2 agonist Pam3CSK4. Left ventricle (LV) performance was evaluated with a pressure-volume microcatheter. Tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and monocyte chemoattractant protein-1 (MCP-1) in the myocardium and plasma were assessed using enzyme-linked immunosorbent assay. Sepsis reduced LV ejection fraction and cardiac output in both young adult and old WT mice. However, identical CLP caused more severe cardiac dysfunction and high mortality in old WT mice that were accompanied by greater levels of TNF-α, IL-1β, IL-6 and MCP-1 in the myocardium and plasma. TLR2 KO diminished aging-related difference in myocardial and systemic inflammatory response, resulting in improved cardiac function and decreased mortality in old septic mice. In addition, higher myocardial TLR2 levels in old WT mice resulted in greater myocardial inflammatory response and worse cardiac dysfunction following administration of TLR2 agonist. Moderate sepsis results in greater cardiac dysfunction and significant mortality in old mice. Aging elevates TLR2 level/activity to exacerbate the inflammatory response to sepsis, leading to worse cardiac dysfunction and mortality.

Simultaneously Assessed Three-Dimensional Speckle-Tracking Echocardiography-Derived Left Ventricular and Left Atrial Volumes Are Associated in Healthy Adults-Findings from the MAGYAR-Healthy Study.

The left atrium (LA) has a significant role in regulating blood flow from veins to the left ventricle (LV). LV performance is affected by several factors including preload, which is partly, but highly, dependent on LA volumes. The aim of the present study is to perform simultaneous assessment of LA and LV volume changes during the cardiac cycle in healthy circumstances. Therefore, LA and LV volumes and volume-based functional properties were determined in healthy adults, and the associations of these parameters were examined. The present study consists of 164 healthy adults (age: 33.0 ± 12.3 years, 82 males) being in sinus rhythm. All subjects have undergone complete two-dimensional Doppler echocardiography with three-dimensional speckle-tracking echocardiography (3DSTE). Increased end-systolic maximum LA volume was associated with higher LV volumes and reduced LV ejection fraction. Very high early pre-atrial contraction and late diastolic LA volumes were associated with increased LV volumes, reduced LV ejection fraction and increased LV mass. Increased LA volumes were associated with increased LV mass. Higher LV volumes were associated with tendentiously higher LA volumes. Higher LV end-diastolic volume was associated with tendentiously higher all LA stroke volumes (SVs) and total and active LA emptying fractions (EFs). Higher LV end-systolic volume was associated with tendentiously higher all LA SVs but preserved all LA EFs. 3DSTE is capable of simultaneous assessment of LA and LV volumes and volume-based functional properties for (patho)physiologic studies. Moreover, 3DSTE-derived LV and LA volumes and functional properties show strong associations.

Circular RNAs dysregulation in ischemic heart failure

Abstract Introduction Circular RNAs (circRNAs) are an emerging class of non-coding RNAs originating from the splicing and circularization of pre-mRNAs and long non-coding RNAs. CircRNAs can regulate transcription and splicing, sequester microRNAs acting as “sponge” and inducing the respective targets, and bind to RNA binding proteins. CircRNAs have been found deregulated in several cardiovascular diseases, including heart failure (HF). However, incomplete and sometimes contradictory results have been reported on their regulation and function in HF, possibly for the heterogeneity of patients analyzed, indicating that our understanding of the regulation and role of cardiac circRNAs is still very limited. Purpose We aim to identify novel circRNA candidates deregulated in ischemic HF and to functionally characterize them in HF. Methods To define the circRNA expression pattern in ischemic HF, a high-depth RNA-seq was performed on the remote zone of left ventricle (LV) samples of 20 non end-stage ischemic HF patients with reduced LV ejection fraction and 20 matched controls. Differentially expressed circRNAs identified using CIRIquant tool were validated by qRT-PCR. Samples from the border zone of non end-stage HF patients and LV biopsies from end-stage HF patients were also used to measure circRNAs expression. Results By RNA-seq, we identified 17 circRNAs as differentially expressed with FDR<0.1. qRT-PCR results confirmed the differential expression of 4 circRNAs, cSLC6A6, cNAA16, cMLIP and cHDCA9, which were upregulated in HF samples (t-test, p-value <0.001). To evaluate circRNAs deregulated independently of their linear counterparts, we also estimated the ratio between circular and linear isoforms. cSLC6A6, cMLIP and cHDCA9 showed also a statistically significant (t-test, p-value <0.002) increase of the circular-to-linear ratio between HF and control patients. To complement the unbiased strategy of RNA-seq, we evaluated the modulation of 18 candidate circRNAs identified by a literature analysis as dysregulated in ischemic or not-ischemic cardiomyopathies or in biological mechanisms relevant for ischemic HF. cPVT1, cANKRD17, cBPTF, displaying a concordant deregulation in different stages of the disease (non end-stage and end-stage HF) and in different regions of LV myocardium (remote and border zone), were chosen for further analysis. Using siRNAs targeting the backsplice junction, cPVT1 was specifically knockdown in a human cardiomyocyte cell line. RNA-seq analysis of cPVT1 knockdown samples identified 3577 significantly differentially expressed genes (FDR<0.01). Gene ontology and pathway analysis showed that these genes were mainly involved in the formation of extracellular matrix, fibrosis and in cellular senescence, suggesting the involvement of cPVT1 in these HF-related disease mechanisms. Conclusion We identified new deregulated circRNAs in ischemic HF patients that might play a pathogenic role in HF. Funding Acknowledgement Type of funding sources: Private hospital(s). Main funding source(s): Italian Ministry of Health, Ricerca Corrente 2021-2023 “CircularRNAs in heart failure: regulation, function and interaction with the transcriptome”

Effect of concomitant surgical atrial fibrillation ablation in patients with reduced left ventricle ejection fraction: A propensity-score matching analysis.

Atrial fibrillation (AF) is common in patients with reduced left ventricle ejection fraction (RLVEF). The impact of concomitant surgical atrial fibrillation ablation (SAFA) in patients with RLVEF is uncertain. The purpose of this study was to assess the outcomes of concomitant SAFA in patients with RLVEF undergoing heart surgery on heart failure (HF) rehospitalization and mortality. Using a local registry and electronic health records linked with provincial civil register survival data from July 2002 to April 2019, we analyzed treatment and outcomes in a cohort of patients with AF and HF defined by left ventricle ejection fraction (LVEF) ≤40%. Health records were used to collect treatment and International Classification of Diseases (ICD 10) codes to determine outcomes. A negative binomial model was used to compare outcomes such as all-cause mortality and rehospitalization for heart failure. The cohort included 682 patients with RLVEF and AF who underwent coronary artery bypass graft and/or valve surgery. A total of 196 patients (29%) underwent concomitant SAFA. After matching, 132 patients with concomitant SAFA were compared to 159 patients who did not undergo concomitant SAFA. At 6.0 ± 3.7 years of follow-up, concomitant SAFA was not associated with lower all-cause mortality (p = .9861) and reduction in rehospitalizations for heart failure decompensation (p = .31) compared to patients who did not have concomitant SAFA performed. Postoperatively, concomitant SAFA might be associated with less vasopressor and mechanical support use (p = .01). Concomitant SAFA during index cardiac surgery is safe but does not reduce mortality or rehospitalizations for HF. The effects of concomitant SAFA in the context of RLVEF needto be better studied with prospective trials.

Echocardiographic characteristics of patients with ischemic and non-ischemic chronic heart failure with reduced ejection fraction

T The data indicate differences in the adverse outcomes of chronic heart failure (CHF) in both ischemic (ICMP) and non-ischemic origins. The knowledge of the structural and functional myocardial state, especially of the left ventricle (LV), is insufficient for accurate risk stratification of unfavorable events in different etiopathogenetic forms of CHF. Aim . To make a comparative analysis of echocardiographic characteristics of CHF patients with reduced LV ejection fraction (EF) ≤35% depending on the origin of CHF. Material and methods. 498 patients of CHF 3-4 functional class of NYHA (New-York Heart Association) with EF ≤35% taking optimal drug therapy were included in the study. Based on the etiology of CHF, two groups of patients with CHF of ischemic genesis (n=254) and dilated cardiomyopathy (DCMP, n=244) were formed. Two-dimensional echocardiography techniques in Band M-mode, color Doppler, and tissue Doppler imaging were carried out. Results. Patients with ICMP and DCMP had the same pattern of LV remodeling (mainly on the type of eccentric hypertrophy), but they reliably differed in the basic parameters of LV architectonics: endsystolic and end-diastolic dimensions, LV volume, LV myocardial mass and values of these indicators, indexed by body surface area. DCMP patients had a higher value of medial-lateral dimension and volume of left atrial, pathological mitral and tricuspid regurgitation was registered more often. Conclusion. It was found that left heart dimensions and volumes of DCMP patients exceed similar parameters in patients with ICMP. The possible association of the results with future adverse outcomes of CHF demands further research.

Impact of Moderate Aortic Stenosis on Long-Term Clinical Outcomes: A Systematic Review and Meta-Analysis.

The clinical course of patients with moderate aortic stenosis (AS) remains incompletely defined. This study sought to analyze the clinical course of moderate AS and compare it with other stages of the disease. Multiple electronic databases were searched to identify studies on adult moderate AS. Random-effects models were used to derive pooled estimates. The primary endpoint was all-cause death. The secondary endpoints were cardiac death, heart failure, sudden death, and aortic valve replacement. Among a total of 25 studies (12,143 moderate AS patients, 3.7 years of follow-up), pooled rates per 100 person-years were 9.0 (95%CI: 6.9 to 11.7) for all-cause death, 4.9 (95%CI: 3.1 to 7.5) for cardiac death, 3.9 (95%CI: 1.9 to 8.2) for heart failure, 1.1 (95%CI: 0.8 to 1.5) for sudden death, and 7.2 (95%CI: 4.3 to 12.2) for aortic valve replacement. Meta-regression analyses detected that diabetes (P = 0.019), coronary artery disease (P = 0.017), presence of symptoms (P< 0.001), and left ventricle (LV) dysfunction (P = 0.009) were associated with a significant impact on the overall estimate of all-cause death. All-cause mortality was higher in patients with reduced LV ejection fraction (<50%) than with normal LV ejection fraction: 16.5 (95%CI: 5.2 to 52.3) and 4.2 (95%CI: 1.4 to 12.8) per 100 person-years, respectively. Compared with moderate AS, the incidence rate difference of all-cause mortality was -3.9 (95%CI: -6.7 to -1.1) for no or mild AS and+2.2 (95%CI:+0.8 to +3.5) for severe AS patients. Moderate AS appears to be associated with a mortality risk higher than no or mild AS but lower than severe AS, which increases in specific population subsets. The impact of early intervention in moderate AS patients having high-risk features deserves further investigation.

Dynamic Trend of Myocardial Edema in Takotsubo Syndrome: A Serial Cardiac Magnetic Resonance Study.

Background: The wall motion abnormalities of the left ventricle (LV) in takotsubo syndrome (TTS) are known to be transient and completely recover within a few weeks. However, there is little information about the relationship between functional recovery and tissue characteristics. The aim of this study was to investigate the recovery process of TTS using cardiovascular magnetic resonance (CMR). Methods: Consecutive patients with TTS were prospectively enrolled. We performed serial CMR in the acute phase (<72 h after admission), the subacute phase (7–10 days after admission) and the chronic phase (3 months later). To assess the degree of myocardial edema quantitatively, we evaluated the signal intensity of myocardium on T2-weighted images and calculated the signal intensity ratio compared with the skeletal muscle. Results: Fifteen patients with TTS were enrolled. CMR demonstrated reduced LV ejection fraction in the acute phase, and it recovered almost completely by the subacute phase. On the other hand, severe myocardial edema was still observed in the subacute phase, associated with increased LV mass. The highest signal intensity ratio in the subacute phase was correlated with the maximum voltage of negative T wave on electrocardiogram (r = 0.57, p = 0.03). Conclusions: In patients with TTS, myocardial edema associated with increased LV mass still remained in the subacute phase despite functional recovery of the LV. Electrocardiogram may be useful to assess the degree of myocardial edema in the subacute phase. Our study suggests that myocardial ischemia might have a central role in developing TTS.

JCS/JHRS 2021 guideline focused update on non-pharmacotherapy of cardiac arrhythmias.

JCS/JHRS 2021 guideline focused update on non-pharmacotherapy of cardiac arrhythmias.

311 A new color Doppler-based echocardiographic technique for evaluation of intraventricular flow dynamics: first application to normal subjects, athletes, and patients

Abstract Aims A new echocardiographic, color Doppler-based technique, named HyperDoppler, has been recently introduced for non-invasive evaluation of intracardiac flow dynamics. The aim of this study was to verify the feasibility and reproducibility of this technique and its capability to differentiate geometrical and energy measures of vortex flow within the left ventricle (LV) in normal subjects, athletes and patients with heart failure. Methods and results Two Italian cardiology centres enrolled each one 100 unselected, consecutive patients presenting at the echocardiography laboratory for a clinical examination, regardless of the indication to echocardiography. In these patients, the feasibility, repeatability, reproducibility, and inter-centre reproducibility of the HyperDoppler technique were tested using the intraclass correlation coefficient (ICC) and Bland–Altman analysis. In addition, 50 normal subjects, 30 professional athletes, and 50 patients with stabilized chronic heart failure and LV ejection fraction &amp;lt;40% were enrolled. Images were acquired using a MyLab X8 echo-scanner and analysed to provide the following vortex flow measures: vortex area, normalized with the LV area; vortex intensity (i.e. the integral of the vorticity inside the vortex), normalized with the total vorticity; vortex depth (the distance of its centre from the LV base) and length along the base-apex direction, both normalized with the LV length; and the total kinetic energy dissipation (KED). Feasibility of HyperDoppler was very high (94.5%). According to the ICC values, at Centre 1 repeatability and reproducibility of vortex flow measures in unselected patients were good for vortex area (0.82, 0.85), length (0.83, 0.82) and depth (0.87, 0.84) and excellent for vortex intensity (0.92, 0.90) and KED (0.98, 0.98). Results of the Bland–Altman analysis showed no bias nor consistent under/overestimations of flow measures, with 95% of points always lying within the limits of agreement for each flow measure. Centre 2 provided similar repeatability and reproducibility evaluations for all the vortex measures, thus supporting a good-to-excellent inter-centre reproducibility. Athletes had greater vortex area, intensity, and KED compared to healthy subjects while they had smaller vortex length and depth and greater KED compared to patients with heart failure and reduced LV ejection fraction. In comparison with healthy subjects, heart failure patients showed greater vortex area, length, depth, and intensity but smaller KED. Combining vortex flow measures, the LV flow profile of healthy individuals, athletes, and heart failure patients could be differentiated. Conclusions HyperDoppler is a new ultrasound technique which is feasible, reliable, and practical for assessment of LV flow dynamics. It can quantitate several measures of the LV vortex and may distinguish normal subjects and patients. Future studies are needed to clarify how to implement this technique in cardiology clinical practice.

ACE Insertion/Deletion gene polymorphism aassociations in STEMI Patients

Abstract Objective ACE Insertion/deletion (I/D) polymorphism has been reported to be associated with various cardiovascular conditions, however its impact in patients with AHF remains controversial. This study aimed to analyze ACE I/D distribution, rate of acute heart failure (AHF) and survival in ST segment elevation myocardial infarction (STEMI) patients. Methods Genomic DNA from 245 STEMI patients and 87 healthy control subjects were analyzed by single polymerase chain reaction method. Based on the ACE I/D genotype STEMI patients were divided with AHF/no AHF, and then - for preserved/reduced ≤40% left ventricle (LV) ejection fraction (EF) to investigate the frequency of the mutant allele D. Results ACE gene polymorphism analyses revealed that D allele had been found more often in STEMI patients than in controls (84.1 vs. 72.4%). The frequency of II, ID, and DD genotypes in STEMI patients was 27.6%, 52.9% and 19.5% compared to 15.9%, 54.3% and 29.8%, respectively in controls with a significant difference in mutant homozygous genotype. Distribution of I/D ACE gene variants among AHF cases vs no AHF, showed similar frequency of II allele (15.8 vs 13.5%), ID allele (54.9 vs 52.8%) and DD allele (29.3 vs 33.7% respectively). In patients with preserved EF there was not statistical significance among different alleles with and without AHF. However, ACE DD polymorphism has been found in AHF patients with reduced EF significantly more often (50.0 vs 30.5%; p&amp;lt;0.05) in compare to AHF patients with preserved EF. Finally, cardiovascular death among all STEMI patients during 3-year follow up was more frequent in patients with DD allele (17.7% vs 5.7% with II and vs 9.9% with ID allele). Conclusion Presented results confirmed ACE DD polymorphism to be associated with higher rate of cardiovascular death and presence of AHF with reduced LV EF in STEMI patients. Future studies are needed to evaluate importance of ACE DD polymorphism in order to find optimal treatment strategies and to prevent negative outcomes in those patients. Funding Acknowledgement Type of funding sources: None.

Surgical Treatment of Left Ventricular Aneurysm Combined with Ischemic Mitral Regurgitation Using a Modified Technique

Background. Ischemic mitral regurgitation (IMR) is the second most common cause of mitral regurgitation (MR). IMR occurs in patients with myocardial infarction due to a rupture of the subvalvular apparatus. Pathological remodel-ing, dilatation and dysfunction of the left ventricle (LV) play a significant role in the development of IMR. The presence of a postinfarction LV aneurysm can lead to the development of MR due to dysfunction, relative and true shortening of the papillary muscles. There are various methods of surgical correction of IMR. The aim. To show the effectiveness of surgical treatment of left ventricular aneurysm combined with ischemic mitral regurgitation using a modified technique. Materials and methods. From January 2011 to December 2019, 20 patients with IMR combined with LV aneurysm underwent surgical intervention using a modified technique at the National Amosov Institute of Cardiovascular Surgery of the NAMS of Ukraine. According to this technique, access to the mitral valve was performed through the left ventricle. The mean age of the patients was 61.2 ± 10.1 years. Among patients with IMR, the majority were men (60.0%). The overwhelming majority of patients (80.0%) had the history of hypertension. Diabetes mellitus was detected in 35.0% of patients. Mitral ring dilatation was observed in 25.0% (5) of the cases, papillary muscle displacement in 40.0% (8), chords rupture in 15.0% (3), papillary muscle infarction in 20.0% (4) of the cases. All the patients had reduced LV ejection fraction with a mean value of 34.5 ± 7.8%. Results. Aortic cross-clamp time through ventricular access was 112.9 ± 18.7 minutes. The duration of mechanical ventilation was 19.1 ± 20.6 hours. The length of stay of patients in the ICU was 99.2 ± 43.5 hours. There were no signs of acute heart failure in the early postoperative period in one in five patients (20.0%). The rate of degree III heart failure after intervention using the modified technique was 20.0% (4). The study of the incidence of cardiac arrhythmias after combined intervention showed that 85.0% (17) of patients operated using the modified technique had no cardiac arrhythmias. Conclusions. In patients who underwent surgery using the modified technique, the mortality rate was 5.0%. This is 1.6-2.8 times less than that in patients undergoing conventional operation. Postoperative occurrence of arrhythmias is much less common than that described in the literature.

Partial cardiac pericyte depletion induces heart failure with reduced ejection fraction

While the critical role of pericytes in maintaining vascular integrity has been extensively demonstrated in the brain and in the retina, very little is known about their role in the heart. To investigate the cardiac structural and functional consequences of partial pericyte depletion (about 60%) in adult mice. To deplete pericytes in adult mice, Pdgfrb-Cre/ERT2; Rosa DTA mice were administered with tamoxifen at 8 weeks of age and again at 10 weeks of age for 5 consecutive days. Control mice were Rosa DTA mice chosen among their littermates and administered with tamoxifen following the same protocol. Cardiac function was assessed via echocardiography and left ventricle (LV) catheterization at 14 weeks of age. Immediately after, mice were sacrificed for histological analyses. Mice depleted with pericytes had a reduced LV ejection fraction (43,9 ± 0,7% vs. 77,6 ± 3,2 in control mice) and an increased end-diastolic pressure (11,12 ± 0,8282 mmHg vs. 5,730 ± 0,9524 in control mice) demonstrating systolic dysfunction. Accordingly, mice depleted with pericytes presented a decreased LV contractility (dP/dtm ax ) (3500 ± 387 mmHg/s vs. 5086 ± 157 in control mice) and an increased LV relaxation time (dP/dtm in ) (−2664 ± 360,3 mmHg/s vs. −4557 ± 192,9 in control mice). Morphologically, the heart of mice depleted with pericytes did not show hypertrophy, however, it presented signs of fibrosis with increased perivascular type I collagen levels and inflammation with an increased CD45 + cell infiltration and endothelial ICAM-1 expression. Cardiac pericyte depletion induces heart failure with reduced ejection fraction demonstrating that cardiac pericytes are critical for cardiac function. This result suggests that pericyte dysfunction could contribute to the onset of heart failure.

Use of beta blockers in dilated cardiomyopathy and relationship with cardiovascular events

Abstract There is an ongoing debate regarding the use of beta blockers (BB) in heart failure with preserved or intermediate ejection fraction. Most studies with BB included patients with moderate to severe left ventricle (LV) dysfunction and some trials challenge the assumption that BB are an effective therapy in these patients. Furthermore, there are some causes of heart failure where the use of BB is not well defined, particularly patients with DCM and mildly reduced LV ejection fraction. Our objective was to analyze the use of beta blockers in patients with dilated cardiomyopathy and to assess its relationship with LV or right ventricle (RV) ejection fraction, late gadolinium enhancement and cardiovascular events (CVE). A retrospective, case control study was designed including 173 patients (mean age 60 years, 73% males, 36% dyslipemia, 30% diabetes, 20% hypertension, 8% currents smoker, 12% previous atrial fibrillation) with diagnosis of DCM and CMR study in our center between 2014–2020 according to the latest European Society of Cardiology (ESC) definition and the latest updated position paper. Clinical data, use of guideline directed medical therapy and devices, cardiac imaging tests, mortality and CVE were collected and analyzed. After a mean follow up of 18 months, 53 patients (30%) suffered a CVE (16% heart failure, 14% incident arrythmia, 0.5% stroke 8% death). The use of beta blockers (n=152; 87%) was associated with a reduced risk for arrythmias (OR=0.019; p=0.0006) in a univariate analysis. It was not associated with RV ejection fraction (p=0.3), hospitalization for heart failure (p=0.03), mortality (p=0.26), or late gadolinium enhancement (p=0.8). For multivariate analyses (log regression, multiple linear regression) we adjusted for age, cardiovascular risk factors, medications, presence of atrial fibrillation, use of devices, LV and RV ejection fraction and presence of late gadolinium enhancement. In our multivariate analyses the use of beta blockers was an independent predictor of improved left ventricle ejection fraction (5.8% mean; p=0.009) and was associated with a marked decrease in the risk of incident arrythmias (OR=0.028; p=0.002) and in mortality (OR=0.068; p=0.041). In patients with DCM, the use of beta blockers is associated with improved LV ejection fraction and a statistically significant reduction in mortality and incident arrythmias. Beta blockers should be recommended irrespective of LV ejection fraction in order to decrease morbidity and mortality in patients with dilated cardiomyopathy. Further studies should assess the contribution of beta blockers in specific etiologies of dilated cardiomyopathy where they could be most helpful and could help to identify the best candidates for early initiation of heart failure therapy. Funding Acknowledgement Type of funding source: None

Duchenne muscular dystrophy: preliminary experience with sacubitril-valsartan in patients with asymptomatic left ventricular dysfunction.

Duchenne muscular dystrophy (DMD) is an inherited X-linked recessive neuromuscular disease caused by mutations of the dystrophin gene, leading to early and progressive muscle deterioration and dilated cardiomyopathy. The aim of this investigation was to assess whether treatment with sacubitril/valsartan (S/V) is well tolerated and may have beneficial effects in DMD patients with left ventricle (LV) dysfunction. We administered S/V to 3 DMD patients (19-29 yeard old) with LV ejection fraction <35% at echocardiography but no symptoms of heart failure. All patients were on optimal medical therapy. S/V was initiated at a very low dose of 12/13 mg/die, after withdrawal of angiotensin-converting enzyme inhibitor therapy, and slowly titrated to the dose of 49/51 mg twice daily or the maximally tolerated dose. Clinical and echocardiographic follow-up was performed after 3, 6 and 12 months. At baseline, the LV ejection fraction was 32±1%. A significant improvement of LV ejection fraction was observed at 3 months (44.0±6.0%; p<0.05), which was maintained at 6 (45.7±5.0%) and 12 (43.3±3.2%) months (p<0.05 for both). No relevant side effects were reported throughout the period of the study. Our preliminary data suggest that, in DMD patients with reduced LV ejection fraction, S/V is safe and may improve LV function.

Cardiac wall motion abnormality as a predictor for undetermined stroke with embolic lesion-pattern

ObjectivesSeveral strokes of potential embolism do not clearly meet the definitions of embolic stroke with unknown source, cryptogenic stroke, or cardioembolic (CE) stroke. Considering the high mortality and recurrence of CE strokes, it is very important to detect treatable cardiac sources of embolism. Although regional wall motion abnormality (RWMA) of the left ventricle (LV) seems to be related to CE stroke, association between cerebral embolic risk and RWMA remains unclear. The purpose of this study was to investigate the influence of RWMA on undetermined stroke with embolic lesion-pattern (USELP). Patients and methodsAmong a total of 2327 patients with acute ischemic stroke, we excluded 148 patients without a transthoracic echocardiography (TTE). According to a stepwise approach, we excluded patients without an embolic lesion-pattern. Finally, we divided patients into two groups (USELP, 119, and non-embolic stroke, 1237). We classified patients’ RWMAs into three major arterial territories according to the standard 17-segment model of TTE. ResultsAmong the included 1356 patients, those with USELP had larger internal dimension at diastole and systole in LV, reduced LV ejection fraction, increased E/A ratios, mitral valve disease, and RWMA. After adjusting for multiple variables, binary logistic regression revealed that RWMA was significantly associated with USELP (OR 7.02, 95 % CI: 3.51–14.01, p<0.001). ConclusionThis study provides significant information to support that RWMA can be a predictor for undetermined embolic stroke. In this regard, RWMA were highly correlated with patients whose imaging supported an embolic source compared to those without this radiographic pattern.

P1338 Anomalous left coronary artery from pulmonary artery syndrome diagnosed in adulthood: case of a mother of five

Abstract Funding Acknowledgements Project no. NVKP_16-1-2016-0017 has been implemented with the support provided from the National Research, Development and Innovation Fund of Hungary Introduction Bland-White-Garland syndrome or ALCAPA (anomalous left coronary artery from pulmonary artery) syndrome is a rare congenital disorder with a prevalence of 1: 300,000. This condition is one the most common causes of infant myocardial infarction. It can ultimately lead to heart failure before the age of one, however when pronounced left and right coronary artery collateralization is present, patients may remain asymptomatic until older age. Due to the development and availability of non-invasive imaging techniques, these patients diagnosed more frequently in recent years. Case description: We present a 53-year-old patient with treated hypertension and five uncomplicated pregnancies. At the age of 40, the patient was referred to coronary angiography due to her dyspnea on exertion. The examination showed that the left main coronary artery (LMCA) originates from the pulmonary artery 7 mm above the pulmonary valve and the right coronary artery is significantly dilated. Based on the mild complaints and good left ventricle systolic function, conservative therapy was recommended by the cardiac surgery team. Since 2018 the patient has had gradually worsening complaints despite of the therapy adjusted for chronic heart failure. Q-waves were depicted on the 12-lead ECG in aVL and V1-V6 leads. Echocardiography showed dilated left ventricle (LV), LV hypertrophy, diffuse hypokinesia, decreased LV systolic function and diastolic dysfunction. At our clinic, we performed cardiac magnetic resonance imaging (CMR) which showed moderately reduced LV ejection fraction, diffuse LV hypokinesia, increased LV volume, septal LV hypertrophy. We visualized the retrograde flow on the LMCA, the shunt volume at the anomalous artery was 1,27 L/min. The CMR also showed irreversible damage of the subendocardial region of the myocardium via late gadolinium enhancement in the area supplied by the LMCA. Since we planned to reevaluate the surgical possibilities, the collateral network with tortuous and dilated left and right coronary arteries were visualized by coronary CT angiography. The surgical team at our institute decided to perform myocardial revascularization and restoration of dual coronary artery supply. Discussion ALCAPA is usually diagnosed in infancy however, in about 10-15% of cases the disease is only recognized in adulthood. The long-term morphological and functional characteristics of the syndrome may include reversible/irreversible ischemic damage, systolic and diastolic dysfunction, mitral regurgitation, significant collateral circulation, left-to-right shunt, dilated coronary arteries. Surgical myocardial revascularization and restoration of dual coronary artery supply is recommended even in adult patients. Abstract P1338 Figure. CTA reconstruction and LGE CMR

Predictors of unfavorable course of acute myocarditis with reduced left ventricular ejection fraction

Early prediction of myocarditis clinical course still remains one of the actual tasks of cardiological science, which has a significant practical value. The purpose of the study was to determine the predictors of unfavorable course of myocarditis with reduced ejection fraction (EF) of the left ventricle (LV) on the basis of follow-up during 24 months. The study included 90 patients with acute myocarditis and reduced LV EF, who were examined in the first month after the disease onset, after 6, 12 and 24 months of follow-up. All patients underwent for echocardiography, Holter monitoring of the electrocardiogram and cardiac magnetic resonance imaging. Statistical processing of the results was performed using the Excel XP software (Місrosoft Office, USA) and Statistica for Windows v. 6.0 (Statsoft, USA). It was found that restoration of cardiac contractility in patients with myocarditis and reduced LV EF began with an increase in the index of LV longitudinal global systolic strain, which occurred 6 months after the debut of the disease and was associated with a decrease in the number of LV segments affected by the inflammatory process, and a significant increase of LV EF and a decrease of LV end-diastolic volume were observed only 1 year after the disease onset. The predictors of cardiovascular events in patients with acute myocarditis during the next 24 months from the onset of the disease, were detected in the 1st month from the debut of the disease and included following pathological changes: value of the LV EF ≤ 30%; reduction of LV longitudinal global systolic strain ≤ 7.0%; evidence of non-sustained ventricular tachycardia, presence of inflammatory changes in ≥6 LV segments, presence of delayed enhancement in ≥ 5 LV segments. Prospects for further research are the creation of registries of patients with myocarditis on the basis of multicenter clinical trial results on a large number of patients surveyed in order to improve diagnosis, prediction of clinical course and identification of early diagnostic markers of cardiovascular events and quantitative risk assessment of their development.

Prognosis after acute coronary syndrome in relation with ventricular–arterial coupling and left ventricular strain

BackgroundThe value of modern non-invasive indices of the left ventricle (LV) and arterial system function, and their interaction for determining prognosis in contemporarily treated patients with acute coronary syndrome (ACS) is not well established. The study aimed to determine the association of ventricular–arterial (VA) coupling, LV global longitudinal peak systolic strain (GLPSS), global strain rate (GSR) and end-diastolic volume at end-diastolic pressure 30mmHg (V30) with long-term clinical outcomes in patients with ACS. MethodsEchocardiography was applied in 569 ACS patients followed up for >12months after hospitalization. Univariate Cox proportional hazard regression models adjusted to various clinical factors, including reduced LV ejection fraction <40%, were used to compare patients between the first and third tertiles of various indices of LV and arterial systems function and their interaction for the prediction of a combined end-point (defined as either stroke, myocardial infarction or death). Results are presented as hazard ratio (HR) with 95% confidence interval (CI). ResultsThere were 57 clinical outcomes during a median follow-up of 625days. Increased VA coupling >1.68 (HR 2.4; 95% CI: 1.04–5.6); V30>107mL (HR 4.5; 95% CI: 1.9–10.6), GLPSS > −12.8% (HR 2.4; 95% CI: 1.02–5.7), GSR > −0.96 1/s (HR 3.8; 95% CI: 1.6–9.1) were robustly associated with increased hazard. ConclusionsWith a sample of contemporarily treated ACS patients, abnormal values of non-invasive indices of LV function and their interaction with arterial system, predict adverse clinical outcomes, independently of LV ejection fraction.

Maternal cardiac remodeling and dysfunction in preeclampsia: a three-dimensional speckle-tracking echocardiography study.

Aims preeclampsia (PE) is a pregnancy complication that remains a main cause of maternal morbidity and mortality. The aims of this study were to investigate left ventricle (LV) performance in PE and to compare maternal cardiac function between early-onset preeclampsia (EP) and late-onset preeclampsia (LP) by novel threedimensional (3D) speckle-tracking echocardiography (STE) parameters while considering LV loading and shape. Methods and Results Two-dimensional echocardiography and 3D STE were performed in 43 women with EP, 41 women with LP, and 81 normal pregnancies. Global longitudinal strain (GLS), global circumferential strain (GCS), global area strain (GAS), and global radial strain (GRS) were measured using 3D speckle-tracking software. There was eccentric hypertrophy and reduced LV ejection fraction (EF) in PE; meanwhile, GLS in EP and LP, GCS in LP, as well as GAS and GRS in EP significantly decreased in PE versus controls. All 3D strain indices were correlated with gestation age. Increased left atrial (LA) volume index was detected in PE. Higher LV mass index and lower 3D-derived strain value were present in women with EP compared to that in women with LP. Conclusion PE cases exhibited significant eccentric hypertrophy, ventricular dysfunction, and LA remodeling. Furthermore, myocardial deformation abnormalities preceded chamber dysfunction in this hypertensive disorder complicated pregnancy. Compared with LP, women with EP demonstrated more remarkable cardiac damage.

Left ventricular early inflow-outflow index: a novel echocardiographic indicator of mitral regurgitation severity.

BackgroundNo gold standard currently exists for quantification of mitral regurgitation (MR) severity. Classification by echocardiography is based on integrative criteria using color and spectral Doppler and anatomic measurements. We hypothesized that a simple Doppler left ventricular early inflow–outflow index (LVEIO), based on flow velocity into the left ventricle (LV) in diastole and ejected from the LV in systole, would add incrementally to current diagnostic criteria. LVEIO was calculated by dividing the mitral E-wave velocity by the LV outflow velocity time integral.Methods and ResultsTransthoracic echocardiography reports from Montefiore Medical Center and its referring clinics from July 1, 2011, to December 31, 2011 (n=11 235) were reviewed. The MR severity reported by a cardiologist certified by the National Board of Echocardiography was used as a reference standard. Studies reporting moderate or severe MR (n=550) were reanalyzed to measure effective regurgitant orifice area by the proximal isovelocity surface area method, vena contracta width, MR jet area, and left-sided chamber volumes. LVEIO was 9.3±3.9, 7.0±3.2, and 4.2±1.7 among those with severe, moderate, and insignificant MR, respectively (ANOVA P<0.001). By receiver operating characteristic analysis, area under the curve for LVEIO was 0.92 for severe MR. Those with LVEIO ≥8 were likely to have severe MR (likelihood ratio 26.5), whereas those with LVEIO ≤4 were unlikely to have severe MR (likelihood ratio 0.11). LVEIO performed better in those with normal LV ejection fraction (≥50%) compared with those with reduced LV ejection fraction (<50%) (area under the curve 0.92 versus 0.80, P<0.001). By multivariate logistic regression analysis, LVEIO was independently associated with severe MR when compared with vena contracta width, MR jet area, and effective regurgitant orifice area measured by the proximal isovelocity surface area method.ConclusionLVEIO is a simple-to-use echocardiographic parameter that accurately identifies severe MR, particularly in patients with normal LV ejection fraction.