Left Ventricle Systolic Dysfunction Research Articles

Echocardiographic study of juvenile dermatomyositis patients: new insights from speckle-tracking-derived strain.

This study aimed to investigate subclinical left ventricle (LV) systolic dysfunction in juvenile dermatomyositis (JDM) using two-dimensional speckle-tracking echocardiography (2DST). Possible associations between LV deformation impairment and disease activity/cumulative damage were also evaluated. Thirty-five consecutive JDM patients without cardiac symptoms and 35 healthy volunteers were enrolled. Clinical data were collected from medical records, and echocardiograms were performed by a pediatric cardiologist, unaware of patients' conditions. Patients and controls had similar age (12.6 ± 0.7 vs.12.5 ± 0.6; p = 0.97) and gender (11F:24M vs.11F:24M; p = 1.0). Median of JDM duration was 4.6 (0.04-17.6) years, and only 6/35 (17%) had active disease (disease activity score (DAS > 3)). Conventional echocardiogram revealed preserved LV ejection fraction (EF) (≥ 55%) in all individuals. In JDM, 2DST identified reduction of LV longitudinal [-22(-17.2 to -27.9) % vs. -23(-20.8 to -27.4) %; p = 0.028)] and circumferential -23.9 ± 2.8% vs. -26.7 ± 2.9%; p = 0.0002) strain. Lower longitudinal strain was associated with DAS >3 -19.9(-17.2 to -26.5)% vs. -22.1-18.9 to -27.9)%; p = 0.046], MDI extent > 0 [-19(-17.2 to -22.5)% vs. -22.1-19.2 to -27.9)%; p = 0.0008], MDI severity > 0 [-19(-17.2 to -22.1)% vs. -22.3(-20.3 to -27.9)%; p = 0.0001] and calcinosis[-20.6(-17.2 to -23)% vs. -22.3(-20.3 to -27.9)%; p = 0.03]. Lower circumferential strain was associated with MDI extent > 0 (-22.1 ± 3.87% vs. -24.4 ± 2.3%; p = 0.039), MDI severity > 0 (-21.7 ± 3% vs. 24.7 ± 2.3%; p = 0.004) and calcinosis (-22.5 ± 3.3% vs. -24.8 ± 2.1%; p = 0.02). There was a negative correlation between longitudinal strain and cumulative dose of prednisone (r = -0.44; p = 0.009) and methotrexate (r = -0.33; p = 0.0008). LV 2DST detected early systolic myocardial compromise in asymptomatic pediatric JDM patients, with preserved EF. Longitudinal strain impairment was associated with disease activity and cumulative damage, whereas circumferential strain impairment was associated exclusively with cumulative damage. • Serious cardiac involvement is rare but has been associated with death in juvenile dermatomyositis. • Two-dimensional speckle tracking stands out for the identification of subclinical myocardial compromise in juvenile dermatomyositis. • Longitudinal strain impairment is associated with disease activity and cumulative damage, whereas circumferential strain impairment is associated exclusively with cumulative damage.

Systolic dysfunction of the subpulmonary left ventricle is associated with the severity of heart failure in patients with a systemic right ventricle

BackgroundThe study aimed to assess the relation between echocardiographic parameters of subpulmonary left ventricular (LV) size and function, and the severity of heart failure in patients with a systemic right ventricle (SRV). Methods and resultsA total of 157 patients (89 post Mustard/Senning operations, 68 with congenitally corrected transposition of great arteries [ccTGA]) were included. The size and function of the SRV and subpulmonary LV were assessed on the most recent echocardiographic exam. Clinical data were collected from the electronic records.The majority (133, 84.7%) were in NYHA functional class 1–2. Median BNP concentration was 79.5[38.3–173.3] ng/l, and 100 (63.7%) patients were receiving heart failure therapy. Both LV and SRV fractional area change (FAC) differed significantly between patients with NYHA class 1–2 vs 3–4 (48[41.5–52.8]% vs 34[28.6–38.6]%, p < 0.0001 and 29.5[23–35]% vs 22[20–27]%, p < 0.0001, respectively), but LV FAC had a higher discriminative power for functional class >2 than SRV FAC (AUC 0.90, p < 0.0001 vs 0.79; p < 0.0001, respectively). A LV FAC cut-off value <39.2% had the highest accuracy in identifying patients with NYHA class 3–4 (sensitivity 83% and specificity 88%). In multivariable logistic regression analysis, LV FAC and SRV FAC independently associated to NYHA class 3–4 (OR 0.80 [95%CI 0.72–0.88], p < 0.0001 and OR 0.85 [95%CI 0.76–0.96], p = 0.007, respectively). ConclusionsSubpulmonary LV systolic dysfunction is associated with NYHA functional class 3–4 in patients with ccTGA or after Mustard or Senning operation. Careful evaluation of the subpulmonary LV should be a part of the routine assessment of patients with a SRV.

Cardio-Protective Effects of Multiport Antegrade Cold Blood Cardioplegia Versus Antegrade Cold Blood Cardioplegia in Patients With Left Ventricular Systolic Dysfunction Undergoing Conventional Coronary Artery Bypass Grafting.

IntroductionThe aim of this study was to compare the in-hospital outcomes of multiport antegrade cold blood cardioplegia through vein grafts versus conventional antegrade cold blood cardioplegia in patients with left ventricle systolic dysfunction who underwent coronary artery bypass grafting (CABG).MethodsThis prospective, randomized clinical study was comprised of patients undergoing on-pump CABG at the Ch. Pervaiz Elahi Institute of Cardiology in Multan, Pakistan from November 18, 2018 to December 17, 2019. Patients with multivessel coronary artery disease and left ventricular systolic dysfunction (ejection fraction < 50%) were included. In Group A (N = 73), multiport antegrade cold blood vein graft cardioplegia was given after every distal anastomosis completed for myocardial preservation. In Group B (N = 73), conventional antegrade cold blood cardioplegia was given for myocardial preservation.ResultsSpontaneous rhythm (without defibrillation applied) after cross-clamp removal was higher in Group A than in Group B (93.3% vs. 85.2%, p < 0.05). Duration of support, ventilation time, and hospital stay were also significantly lower in Group A than in Group B with p = 0.00001, p = 0.03, and p = 0.002, respectively. Intra-aortic balloon pump insertion (4.1% vs. 23.0%, p = 0.02) and operative mortality (0.5% vs. 4.0%, p = 0.35) were also lower in Group A than in Group B. Postoperative left ventricular ejection fraction (LVEF) increased more in Group A than in Group B, and the postoperative LVEF mean value was 44.68% in Group A versus 41.26% in Group B (p = 0.02).ConclusionMultiport vein graft blood cardioplegia provides superior myocardial protection in patients with left ventricular systolic dysfunction who underwent CABG. It is also easy to administer, so this technique can be adopted as a routine method for myocardial protection in patients with left ventricular dysfunction planned for on-pump CABG.

Exercise preconditioning prevents left ventricular dysfunction and remodeling in monocrotaline-induced pulmonary hypertension.

Background:Despite pulmonary arterial hypertension (PAH) directly affects the right ventricle (RV), important structural, functional, and molecular changes also occur in left ventricle (LV). The objective of our study was to analyze the hypothetical cardioprotective effects of exercise preconditioning on LV in rats with monocrotaline (MCT)-induced PAH.Methods:Forty male Wistar rats were randomly separated in sedentary (SED) and trained group (EX; running sessions of 60 min/day, 5 days/wk, at 25 m/min, for 4 weeks). After 4 weeks, animals were injected with MCT (60 mg/kg; SED + MCT; EX + MCT) or vehicle (SED + V). Following an additional period of 4 weeks where all animals remained sedentary, we completed LV hemodynamic evaluation in baseline and isovolumic conditions and collected LV samples for histological and molecular analysis.Results:Preconditioning with exercise was capable to restore LV systolic and diastolic dysfunction in both baseline and isovolumic conditions (P < .05). This improved was paralleled with prevention of LV cardiomyocytes atrophy, fibrosis, and endothelin 1 mRNA levels (P < .05).Conclusions:Our findings suggest that exercise preconditioning can prevent LV dysfunction secondary to MCT-induced PAH, which is of particular interest for the familial form of the disease that is manifested by greater severity or earlier onset.

The value of 2D speckle-tracking strain echocardiography in evaluating the relationship between carotid elasticity and left ventricular systolic function in patients with diabetic nephropathy

ObjectiveTo investigate the relationship between the elasticity of the carotid artery and the LV (left ventricle) systolic function in patients with diabetic nephropathy (DN) by using two-dimensional speckle-tracking strain echocardiography (2D-STE).MethodsDN patients (n = 108) and control subjects (n = 112), all of whom underwent echocardiography and carotid ultrasound. Analysis of LV GLS (global longitudinal strain) from the apical two-chamber (2C), three-chamber (3C), and four-chamber (4C) views. Meanwhile, the circumferential strain (CS) of the carotid artery was obtained from the view of the short-axis right common carotid artery. The differences between the two groups were compared, and a correlation analysis between CS and GLS was performed.ResultsThe 4CGLS, 2CGLS, 3CGLS, and CS of the DN group were significantly lower at significant levels in contrast to the control group (p < 0.05). There was a significantly positive correlation of CS with 4CGLS, 2CGLS, and 3CGLS in all subjects (r = 0.809, p = 0.000; r = 0.830, p = 0.000; r = 0.830, p = 0.000, respectively).Conclusion2D-STE is a relatively new technique for assessing the mechanical characteristics of the carotid artery in patients with DN. Reduced values of CS correlate with reduced LV systolic function as evaluated by strain measurements, which can predict the risk of systolic dysfunction of LV.

Subtle cardiac dysfunction in nephropathic cystinosis: insight from tissue Doppler imaging and 2D speckle tracking echocardiography.

Nephropathic cystinosis is a rare autosomal recessive lysosomal storage disorder that initially affects the kidney progressing to multi-organ failure due to accumulation of cystine in all tissue compartments. The main objective of this study is the evaluation of cardiac function in cystinosis patients using non-conventional echocardiographic modalities like pulsed wave tissue Doppler imaging (PW-TDI) and 2D speckle tracking echocardiography (2D-STE). This is a case control study conducted on fifteen patients with cystinosis and 15 normal controls. Echocardiography was done for all participants and PW-TDI was performed for measurement of S', E', A' velocities and myocardial performance index (MPI) at basal parts of septal, left ventricle (LV), and right ventricle (RV) free walls. 2D-STE was done for evaluation of global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) of LV. Mitral E and A velocities and tricuspid annular plane systolic excursion (TAPSE) were also measured. The GLS, GRS, and S' velocity at basal septum and LV lateral wall were significantly lower in patients denoting LV systolic dysfunction (p = 0.005, p < 0.0001, p = 0.001, p = 0.006, respectively), while E/E' were significantly higher in patients group denoting LV diastolic dysfunction (p < 0.001). For RV function, TAPSE, S', and E' velocity were significantly lower in patients group (p 0.013, p < 0.01, p = 0.05, respectively) indicating RV systolic and diastolic dysfunction. The TDI-derived MPI for both LV and RV were significantly higher in patients group (p < 0.0001, p < 0.01, respectively) indicating both ventricular systolic and diastolic dysfunction. For prediction of cardiac dysfunction among patients, the receiver operating characteristic (ROC) curve showed that GRS ≤ 29% had sensitivity 93.3% and specificity 100%, GLS > - 20.1% had sensitivity 66.7% and specificity 93.3%, LV-E/E' >7.87had sensitivity 73.3% and specificity 93.3%, and MPI-LV > 0.36 had sensitivity 100% and specificity 93.3% while MPI-RV > 0.29 had sensitivity 80% and specificity 93.3% and TAPSE ≤ 19mm had sensitivity 80% and specificity 73.3%. Patients with cystinosis have significant both left and right ventricular dysfunction, which can be better evaluated using the non-conventional echocardiographic modalities like TDI and 2D-STE for early detection of subtle cardiac dysfunction.

Association between right ventricle dysfunction and poor outcome in patients with septic shock

ObjectiveSepsis-induced myocardial dysfunction (SIMD) can involve both the left and right ventricles. However, the characteristics and outcomes across various manifestations of SIMD remain unknown.MethodsThis was a retrospective cohort study using...

Fetal aortic annular growth in the “borderline” left heart varies by cardiac phenotype

Purpose: Two “borderline” left heart phenotypes are evident in the fetus: 1) severe aortic stenosis (AS), which is associated with a globular left ventricle (LV), systolic LV dysfunction, and LV growth arrest, and 2) left heart hypoplasia (LHH) which is associated with a “long, skinny” LV, laminar flow across hypoplastic mitral and aortic valves, and arch hypoplasia. Both phenotypes may be counseled for possible single ventricle palliation. We aimed to compare the rates of aortic valve annulus size and Z-score change over gestation by phenotype. We hypothesized that the …

Accelerated Hypofractionated Whole Breast Radiotherapy for Early Breast Cancer; ARandomized Phase III Clinical Trial

To compare the cosmetic outcome and acute cutaneous, cardiac, and pulmonary toxicity profile of accelerated hypofractionated and conventional whole breast radiotherapy (WBRT).This was a blocked randomized, clinical trial on women with early-stage node-negative invasive breast cancer after breast conservation surgery (BCS) with clear margins randomly assigned to receive WBRT either at a conventional dose of 50.0 grays (Gy) in 25 fractions (the conventional group) or at a dose of 42.5 Gy in 16 fractions (the hypofractionated group). Boost irradiation was permitted in both groups. Data were analyzed by SPSS V21.0 using Mann–Whitney U, independent-samples t- and Chi-Square/Fisher's exact tests at the level of P≤0.05.The median follows up was 16 months. Forty-one patients in the conventional WBRT arm and 45 patients in the hypofractionated WBRT group were enrolled. No significant difference was observed in terms of left and right ventricle systolic dysfunction and diastolic dysfunction. Pulmonary function tests after 6 and 12 months follow up, were comparable in both groups (P=0.2). Skin toxicity during and after treatment was acceptable in both groups. Breast size change in the conventional and the hypofractionated WBRT groups was 14.3% and 7.1%, respectively (P=0.6). Excellent or good cosmetic outcome was similar in both groups.The results of our study support the use of accelerated hypofractionated WBRT in women with invasive breast cancer less than five cm and node-negative after breast-conserving surgery, which provides a more convenient shorter course of radiotherapy with a comparable cosmetic outcome and cutaneous, cardiac, and pulmonary toxicity profile.

P1133Impact of mid-septal versus apical pacing on the right ventricle performance of patients with right bundle branch block undergoing pacemaker implantation

Abstract Background pacemaker induced cardiomyopathy or transient impairment of the left ventricle (LV) function could be common collateral effects of the prolonged right ventricle (RV) pacing in patients with a pacemaker (PM) and pre-existing intra-ventricular conduction disturbances. However, the impact of RV pacing-site on RV performance of patients with right bundle branch block(RBBB) is still under-investigated. Purpose to study the effects of RV pacing in the mid-septal versus apical site on the morpho-functional performance of RV in patients undergoing permanent PM implantation. Methods We prospectively enrolled consecutive patients with a pre-existent complete RBBB and undergoing dual-chamber PM implantation in our institution. We randomized the patients 1:1 to receive the RV catheter fixed either in the apex or in the mid-septal position. Patients with LV systolic dysfunction (LVEF &amp;lt;50%), severe valvulopathies, left bundle branch block (LBBB), or preserved intraventricular conduction were excluded. Patients who received PM implantation were evaluated both at baseline and after two months with a 12-lead ECG, 2D, and 3D echocardiogram with analysis focused on RV performance according to the guidelines of the European Association of Cardiovascular Imaging. Results a total of 22 patients were randomized in the study, 11 (50%) received RV catheter positioned in the apex and 11 (50%) in the mid-septum, respectively. No baseline differences were recorded between the two groups in clinical characteristics, ECG and echocardiographic parameters. At 2 months follow up, there were no statistically significant difference in the % of RV pacing between the two groups. Nonetheless, RV mid-septal group showed significantly shorter duration of the stimulated QRS (146 ± 12 msec vs. 161 ± 20 msec, p = 0.05), significantly reductions in the RV dimensions (pre: 42 ± 8 mm vs. post: 37 ± 7 mm, p = 0.05) telediastolic area (pre: 12 ± 3 cm2/m2 vs post: 9 ± 4 cm2/ m2, p = 0.02) telediastolic volume (pre: 55 ± 16 ml/m2 vs post: 50 ± 17 ml/m2, p = 0.02) and a significant improvement of RV ejection fraction (pre: 54 ± 9% vs post: 57 ± 11%, p = 0.02) than patients in the RV-apical group. Moreover, patients in the RV-apical group showed significant lowering in the GLS of the LV (pre: -16 ± 3% vs post: -11.7 ± 3%, p &amp;lt;0.001) and in the TAPSE (pre: 23 ± 5 mm vs post: 21 ± 2, p = 0.07) at follow up. Conclusions In this study, mid-septal pacing seems associated with a better morpho-functional RV performance than apical pacing in patients with pre-existent RBBB undergoing permanent PM implantation.

P341Life-threatening events in patients with non-compaction cardiomyopathy and mutations in ion channel genes

Abstract Purpose to analyze life-threatening events during follow-up in patients with non-compaction cardiomyopathy (NCCM) who have mutations in the genes responsible for the functioning of ion channels. Methods the study included 64 unrelated pts (aged 38.63 ± 14.72 years, 34/53.12% male, LVEF 43.02 ± 8.65%) with criteria of NCCM confirmed by imaging techniques (echocardiography (Jenni) and cardiovascular magnetic resonance (Petersen). Mutation search was carried out by the next generation sequencing (NGS). Pathogenic mutations or rare substitutions with possible clinical significance were found in 12 unrelated pts in the ion channel genes: KCNH2, KCNJ2, CACNA1C, RYR2, HCN4, TRPM4, PKP2, TRPM4. Mutations in other genes (PLN, DSP, NOTCH1, RBM20) were detected in 4 pts (1 pathogenic and 3 VUS). Results mutations in genes associated with long QT syndrome (LQTS) were found in 5 pts with NCCM: c.3107G &amp;gt; A (p.Gly1036Asp), с.2653С&amp;gt;T (p.Arg885Cys) in KCNH2 gene (16.7%); c.T28076 (p.F936C) in CaCNA1C gene (8.3%); c.1165G &amp;gt; C (p.Asp389Asn) in KCNJ2 gene (8.3%). There was no prolongation of the QTc interval &amp;gt; 480 msec on ECG; frequent episodes of nonsustained ventricular tachycardia (VT) were recorded on 24-hour ECG-monitoring. During the follow-up period (median follow-up of 2.4 years), two pts with mutations in KCNH2 genes with suddenly developed sustained VT were implanted with ICD. A 32-year-old patient with a mutation in CACNA1C gene and ST-elevation myocardial infarction of thromboembolic genesis underwent PCI. 58-year-old patient with widening of QRS &amp;gt; 130 msec and frequent paroxysms of nonsustained VT was implanted with CRT-D. An ICD was implanted in a 60-year-old patient with a mutation c.12665_12667del(p.4223del) in the RYR2 gene and suddenly developed a sustained VT. In the remaining two pts with RYR2 gene mutations c.12272C &amp;gt; T (p.Ala4091Val), c.12944G &amp;gt; A(p.Gly4315Glu), frequent episodes of nonsustained VT were recorded, which were corrected medically. Orthotopic heart transplantation and Accucinch transcatheter direct mitral valve annuloplasty system implantation were performed in two pts with ventricular tachyarrhythmias and severe systolic and diastolic dysfunction of the left ventricle with mutations c.3224T &amp;gt; C (p.Leu1075Pro), c.1459_1494del36 (p.Lys487_Leu498del) in the TRPM4 gene. In other pts with mutations in HCN4 (8.3%), DPP6 (8.3%), PKP2 (8.3%) genes ventricular tachyarrhythmias were treated with antiarrhythmic drugs. Conclusion the presence of mutations in the genes controlling the functioning of ion channels is an additional risk factor for adverse events in patients with NCCM.

Adenosine kinase inhibition enhances microvascular dilator function and improves left ventricle diastolic dysfunction.

Inhibition of adenosine kinase (ADK), via augmenting endogenous adenosine levels exerts cardiovascular protection. We tested the hypothesis that ADK inhibition improves microvascular dilator and left ventricle (LV) contractile function under metabolic or hemodynamic stress. In Obese diabetic Zucker fatty/spontaneously hypertensive heart failure F1 hybrid rats, treatment with the selective ADK inhibitor, ABT-702 (1.5mg/kg, intraperitoneal injections for 8-week) restored acetylcholine-, sodium nitroprusside-, and adenosine-induced dilations in isolated coronary arterioles, an effect that was accompanied by normalized end-diastolic pressure (in mmHg, Lean: 3.4±0.6, Obese: 17.6±4.2, Obese+ABT: 6.6±1.4) and LV relaxation constant, Tau (in ms, Lean: 6.9±1.5, Obese: 13.9±1.7, Obese+ABT: 6.0±1.1). Mice with vascular endothelium selective ADK deletion (ADKVEC KO) exhibited an enhanced dilation to acetylcholine in isolated gracilis muscle (lgEC50 WT: -8.2±0.1, ADKVEC KO: -8.8±0.1, P<.05) and mesenteric arterioles (lgEC50 WT: -7.4±0.2, ADKVEC KO: -8.1±1.2, P<.05) when compared to wild-type (WT) mice, whereas relaxation of the femoral artery and aorta (lgEC50 WT: -7.03±0.6, ADKVEC KO: -7.05±0.8) was similar in the two groups. Wild-type mice progressively developed LV systolic and diastolic dysfunction when they underwent transverse aortic constriction surgery, whereas ADKVEC -KO mice displayed a lesser degree in decline of LV function. Our results indicate that ADK inhibition selectively enhances microvascular vasodilator function, whereby it improves LV perfusion and LV contractile function under metabolic and hemodynamic stress.

Assessment of Global Longitudinal Strain in Patients Receiving Renal Replacement Therapy With Preserved Left Ventricular Ejection Fraction

BackgroundPatients with chronic kidney disease, including those on renal replacement therapy (RRT), have higher cardiovascular mortality. Global longitudinal strain (GLS) detects subtle changes in the left ventricle (LV) and constitutes a more sensitive predictor of cardiovascular mortality than the LV ejection fraction (LVEF). The aim of this study was to assess the prevalence of impaired GLS among patients on RRT with preserved LVEF. We also aimed to identify the possible clinical factors responsible for GLS impairment. MethodsA total of 108 patients on RRT with preserved LVEF and no history of cardiac disease were evaluated. We assessed echocardiogram parameters with a calculation of GLS, laboratory parameters, presence of diabetes, hypertension, duration of hemodialysis (HD), and the time after kidney transplantation (KTx). An impaired GLS value was set at ≥-18%. The multivariate stepwise logistic regression analysis was used to identify the factors related to impaired GLS. ResultsAmong 108 patients aged 58.5 ± 13.5 on RRT with preserved LVEF, 45% had GLS ≥-18% (62% on HD, 39% after KTx). The ROC analysis revealed that the cutoff point for the predicted GLS ≥-18% by HD duration was more than 28 months (0.75 [95% CI 0.66-0.84]; P < .001). In multivariate stepwise logistic regression analysis, a duration of HD longer than 28 months was associated with GLS ≥-18%. ConclusionsAbout 45% patients on RRT, despite preserved LVEF and no history of heart diseases, had LV systolic dysfunction defined as GLS ≥-18%. HD longer than 28 months significantly increases the risk of GLS impairment in patients on RRT.

Inflammation due to Chronic Alcohol Exposure Promotes Cardiac Atrophy and Dysfunction Resulting from Impaired Fibroblast‐Myocyte Crosstalk

Alcoholic cardiomyopathy (ACM) is a cardiac disease caused by chronic heavy alcohol abuse. ACM is most notably a type of dilated cardiomyopathy (DCM), accounting for approximately 21–50% of all idiopathic non‐ischemic DCM cases in Western countries. ACM is typically characterized by left ventricular dilation and LV muscle wasting (atrophy), with diastolic and systolic dysfunction (ejection fraction &lt; 40%) occurring in later stages. Previous studies in our lab have shown that chronic alcohol exposure prevents compensatory hypertrophy in both volume‐ and pressure‐overload models of heart failure. However, the mechanisms of alcohol‐induced cardiac atrophy and dysfunction are not clear. The purpose of this study was to investigate mechanisms of chronic alcohol‐induced cardiac remodeling and dysfunction. We also sought to determine the role of cardiac fibroblasts, which play a dynamic role in cardiac remodeling, in mediating these effects.Adult male Wistar rats were exposed to ethanol (EtOH) vapor inhalation for 16 weeks. Echocardiography was performed to assess terminal cardiac structure and function. Cardiac fibroblasts were isolated from the left ventricle (LV) for both ex vivo and in vitro analysis. Gene expression was determined by real‐time PCR and flow cytometry. Protein expression was determined via Western blot analysis. EtOH led to cardiac wall thinning and impaired systolic function, as evident by decreased LV wall thickness at diastole (LVPWd) and fractional shortening, respectively, Additionally, EtOH decreased mRNA levels of various contractile proteins including Acta1, Actc1, and Myh7. EtOH also increased mRNA and protein levels of LV inflammatory markers, TNF‐α and NF‐κB. Furthermore, EtOH induced increased activation of JNK and decreased mTOR activation, suggestive of decreased hypertrophic signaling and atrophy. EtOH led to myofibroblast activation as assessed by flow cytometry and led to ECM remodeling (increased collagen III content). EtOH increased Tnf and Il6 mRNA in cardiac fibroblasts ex vivo, and increased mRNA levels of several pro‐inflammatory cytokines and chemokines in vitro. Administration of conditioned media from EtOH‐treated fibroblasts decreased contractile protein mRNA levels and impaired Akt and mTOR signaling in differentiated H9C2 cardiomyocytes.Our results indicate that EtOH‐induced cardiac atrophy and dysfunction is associated with activation of inflammatory pathways. Furthermore, EtOH may induce a pro‐inflammatory cardiac fibroblast phenotype, leading to aberrant fibroblast‐myocyte cross‐talk.Support or Funding InformationFunding provided by the NIH/NIAAA 1R21AA022690 (JDG) and the Saving tiny Hearts Society (JDG).

Numerical Study of Atrial Fibrillation Effects on Flow Distribution in Aortic Circulation

Atrial fibrillation (AF) is the most common type of arrhythmia, which undermines cardiac function. Atrial fibrillation is a multi-facet malady and it may occur as a result of other diseases or it may trigger other problems. One of the main complications of AF is stroke due to the possibility of clot formation inside the atrium. However, the possibility of stroke occurrence due to the AF and the location from which an embolus dispatches are subject of debate. Another hypothesis about the embolus formation during AF is thrombus formation in aorta and carotid arteries, embolus detachment and its movement. To investigate the possibility of the latter postulation, the current work suggests a parametric study to quantify the sensitivity of aortic flow to four common AF traits including lack of atrial kick, atrial remodelling, left ventricle systolic dysfunction, and high frequency fibrillation. The simulation was carried out by coupling several in-house codes and ANSYS-CFX module. The results reveal that AF traits lower flow rate at left ventricular outflow tract, which in general lowers blood perfusion to systemic, cerebral and coronary circulations. Consequently, it leads to endothelial cell activation potential (ECAP) increase and variation of flow structure that both suggest predisposed areas to atherogenesis and thrombus formation in different regions in ascending aorta, aortic arch and descending thoracic aorta.

Coronary slow flow is associated with a worse clinical outcome in patients with Takotsubo syndrome

ObjectivePatients with Takotsubo syndrome (TTS) present an acute microvascular dysfunction that leads to an impaired myocardial perfusion and, in more severe forms, an impaired epicardial flow. However, clinical relevance of...

P1274 Early surgery versus watchful waiting in patients with moderate aortic stenosis and left ventricular systolic dysfunction

Abstract Background Aortic stenosis (AS) induces significant pressure overload to the left ventricle (LV) and its burden may increase if there is concomitant LV systolic dysfunction. Severe AS with LV systolic dysfunction is a class I indication for aortic valve replacement (AVR) irrespective of symptoms, however, this recommendation is not well established in those with moderate AS and LV systolic dysfunction. In this study, we sought to investigate the clinical impact of surgical AVR among patients with moderate AS and LV systolic dysfunction. Methods From 2001 to 2017, we retrospectively but consecutively identified patients with moderate AS and LV systolic dysfunction from a single tertiary hospital. Moderate AS was defined as aortic valve area between 1.0 and 1.5cm2 and LV systolic dysfunction as LV ejection fraction less than 50%. The primary outcome was all-cause death and we additionally analyzed cardiac death as a secondary endpoint. The outcomes were compared between those who underwent early surgical AVR at the stage of moderate AS versus those who were followed without AVR at the outpatient clinic. Results Among a total of 257 patients with moderate AS and concomitant LV systolic dysfunction (70.0 ± 11.3 years, 63.4% of male), 34 patients received early AVR. Patients in the AVR group was younger than the observation group (64.2 ± 8.1 vs. 70.9 ± 11.5, respectively), and had a lower prevalence of hypertension and chronic kidney disease. During a mean of 3-year follow up, 112 patients (47.5%) died and the overall death rate was 15.367 per 100 person-year (PY). The AVR group showed a significantly lower rate of all-cause death than the observation group (5.241PY vs. 18.160PY, p-value = 0.002). After multivariable Cox proportional hazard regression adjusting for age, sex, comorbidities and laboratory data, early AVR at the stage of moderate AS significantly reduced the risk of all-cause death (hazard ratio [HR] 0.340, 95% confidence interval [CI] 0.117 - 0.985, p-value = 0.047). However, there was no risk reduction of cardiac death (HR 0.578 95% CI 0.150 - 2.231, p-value = 0.426). Conclusions In patients with moderate AS and LV systolic dysfunction, AVR reduces the risk of all-cause death. A prospective design study is warranted to confirm our findings in the near future. Abstract P1274 Figure. Kaplan-Meier curves for deaths

Contribution of cardiac resynchronization therapy in hypertrophic cardiomyopathy with systolic dysfunction: A case-control study

Cardiac resynchronization therapy (CRT), known as an effective treatment for heart failure in dilated cardiomyopathy (DCM), remains uncertain in hypertrophic cardiomyopathy (HCM), with conflicting results reported from previous studies. We aimed to study the efficiency of CRT in patients with HCM, heart failure and left ventricle systolic dysfunction. From implantable cardioverter defibrillator (ICD) data-base of a single university center, patients with HCM, who received CRT, were identified and matched with resynchronized DCM in a 2:1 ratio on age at implantation (± 5 years), gender and left ventricular ejection fraction (LVEF) at implantation (± 5%). Clinical, electro-cardiographic and echocardiographic parameters were gathered at 1–6 months, 6–12 months and last follow-up after implantation. Between 2007 and 2018, we included 18 HCM patients (women 7(39%); at ICD implantation, age 59 ± 9 years, LVEF 38 ± 6%, NYHA class 2.8 ± 0.4) matched with 36 controls. At one year after implantation, the relative median change from baseline showed better improvement in HCM patients regarding: 1/NYHA class (−50% vs. − 20%, P < 0.001), 2/LVEF (+ 30% vs. + 6%, P < 0.01), 3/left ventricular end-systolic (LVES) volume (− 39% vs. − 21%, P < 0.01), 4/cardiac output (+ 18% vs. + 5%, P < 0.001) and 5/BNP (− 51% vs. − 24%, P = 0.02). HCM patients retained the benefit of CRT at last follow-up (41 ± 24 months) for NYHA (− 33% vs. − 12%, P < 0.01), LVEF (− 36% vs. − 11%, P < 0.01), LVES volume (− 42% vs. − 20%, P = 0.01) and cardiac output (+1 8% vs. − 2%, P < 0.001). The rate of bi-ventricular pacing (98% vs. 99%, P = 0.81) and the QRS duration (130ms vs. 130ms, P = 0.57) at one year after CRT were comparable in the both groups. Among HCM patients, 2 (11%) of them died and 2 (11%) had a heart transplant. CRT improved heart failure symptoms and carried out reverse remodeling of the left ventricle in HCM with better outcomes than in DCM in long-term follow-up.

P362 Antimalarial-induced cardiomyopathy: retrospective case series

Abstract Background Antimalarial drugs chloroquine and hydroxychloroquine represent an important therapeutic option in autoimmune diseases. Rare cases of potentially lethal antimalarial-induced cardiomyopathy (AMIC) have been described. Pattern of minimal changes with wall hypertrophy, followed by restrictive and end-stage dilative cardiomyopathy was proposed in AMIC. Purpose Our aim was to identify patients with definite AMIC and characterize their clinical and imaging findings. Methods Retrospective analysis of admissions to Cardiology department from January 2010 to January 2019 was done to identify patients with definite diagnosis of AMIC based on positive endomyocardial biopsy. Clinical, echocardiographic, and cardiac magnetic resonance (CMR) imaging findings were reviewed if available. Results Three patients with biopsy proven diagnosis of AMIC were identified. Two patients, 62 and 76-year-old females, presented with signs of congestive heart failure, while the third, a 41-year-old man presented with chest pain and cardiac conduction abnormalities necessitating pacemaker implantation. All were treated with chloroquine phosphate. Both females had a history of pacemaker due to atrioventricular block. All had positive troponin and coronary artery disease was excluded. Echocardiography in the first case showed a severely dilated left ventricle (LV) with global hypokinesia and severe systolic dysfunction (LVEF 30%). CMR confirmed dilative cardiomyopathy, furthermore subepicardial late gadolinium enhancement (LGE) of the inferolateral LV wall and of the right ventricle free wall was present. In the second case a restrictive cardiomyopathy pattern was observed with mild biventricular systolic dysfunction and biatrial enlargement. CMR of this case was not available. Echocardiography in the third case showed a normal sized LV with mild diastolic and systolic dysfunction (LVEF 50%), along with septal hypokinesia. CMR showed patchy subepicardial and mid-wall LGE of the septum that was falsely attributed to myocarditis. Additionally, a chemical shift artefact suggestive of myocardial fatty infiltration (Image 1) was visible in the apical septum. After discontinuation of chloroquine two patients improved, while the first patient deteriorated and eventually succumbed to refractory heart failure. Conclusions Our three cases confirm high diversity of cardiac imaging findings in AMIC. Even mild non-specific findings such as LV systolic dysfunction or wall motion abnormalities in patients on antimalarial drugs should therefore be thoroughly investigated. CMR with non-ischaemic LGE pattern may aid in diagnosis, however definite diagnosis is currently possible only with endomyocardial biopsy. Novel imaging techniques, such as T1 mapping, have a potential to increase the diagnostic yield given the known patohistological similarities between AMIC and Anderson-Fabry disease. Abstract P362 Figure. Chemical shift artefact (arrow) in AMIC

P1284 The role of three-dimensional echocardiography in the evaluation of geometry and function of the left ventricle in patients with chronic chagas cardiomyopathy

Abstract BACKGROUND A hallmark of chronic Chagas" cardiomyopathy (CCC) is the early appearance of regional wall motion abnormalities of the left ventricle (LV), especially in the lateral and apical regions. The morphological and functional assessment of LV by two-dimensional (2D) echocardiography, besides depending on geometric assumptions, may not include the most affected segments. The three-dimensional (3D) method offers advantage for the quantification of chamber volumes, but its role in the assessment of patients with CCC is not well established. PURPOSE: The aim of this study is to evaluate the concordance between 3D and 2D methods in the quantification of left ventricular end-diastolic volume (LVEDV) and left ventricular ejection fraction (LVEF) in patients with CCC. METHODS: 44 patients with CCC were selected. Seven subjects were excluded from the analysis (3 for atrial fibrillation, 1 for frequent ventricular extrasystoles, 3 for inadequate acoustic window), resulting in 37 patients. Subjects were submitted to 2D and 3D transthoracic echocardiography by a single experienced examiner following the recommendations from the chamber quantification guidelines. The concordance between the methods was evaluated using the Lin concordance correlation coefficient (CCI) and the Bland-Altman graph analysis. Descriptive analyses of the percentage of individuals reclassified as to altered or to non altered-LVEDV and LVEF values were performed using normal values of 3D as a reference. RESULTS: Age = 58 ± 12 years, 54% men. LVEF-2D = 47 ± 9% and LVEDV- 2D = 73 ± 18 ml / m². The CCI for the measurements of LVEDV and FEVE by both methods was 0.861 and 0.833, respectively. The mean difference found was 3 mL for LVEDV and 3% for LVEF. The 95% agreement limits found were (-14, 20 ml) for LVEDV and (-5; 11%) for LVEF. When assessed with 2D, 27% of individuals previously classified as having LV enlargement were reclassified as having normal LV volumes using the 3D method. Conversely, regarding LVEF, 16% of individuals considered normal by 2D were reclassified as having reduced LVEF with the 3D method. CONCLUSION: In individuals with CCC measurements of LVEDV and LVEF by 3D and 2D methods show high agreement. However, 3D evaluation allows the reclassification of 27% and 16% of the individuals regarding the presence of LV dilatation and LV systolic dysfunction, respectively. Abstract P1284 Figure. Bland-Altman plot - LVEF