Development Of Systolic Dysfunction Research Articles

Risk factors and outcomes associated with systolic dysfunction following traumatic brain injury.

Systolic dysfunction has been observed following isolated moderate-severe traumatic brain injury (Ims-TBI). However, early risk factors for the development of systolic dysfunction after Ims-TBI and their impact on the prognosis of patients with Ims-TBI have not been thoroughly investigated. A prospective observational study among patients aged 16 to 65 years without cardiac comorbidities who sustained Ims-TBI (Glasgow Coma Scale [GCS] score ≤12) was conducted. Systolic dysfunction was defined as left ventricular ejection fraction <50% or apparent regional wall motion abnormality assessed by transthoracic echocardiography within 24 hours after admission. The primary endpoint was the incidence of systolic dysfunction after Ims-TBI. The secondary endpoint was survival on discharge. Clinical data and outcomes were assessed within 24 hours after admission or during hospitalization. About 23 of 123 patients (18.7%) developed systolic dysfunction after Ims-TBI. Higher admission heart rate (odds ratios [ORs]: 1.05, 95% confidence interval [CI]: 1.02-1.08; P = .002), lower admission GCS score (OR: 0.77, 95% CI: 0.61-0.96; P = .022), and higher admission serum high-sensitivity cardiac troponin T (Hs-cTnT) (OR: 1.14, 95% CI: 1.06-1.22; P < .001) were independently associated with systolic dysfunction among patients with Ims-TBI. A combination of heart rate, GCS score, and serum Hs-cTnT level on admission improved the predictive performance for systolic dysfunction (area under curve = 0.85). Duration of mechanical ventilation, intensive care unit length of stay, and in-hospital mortality of patients with systolic dysfunction was higher than that of patients with normal systolic function (P < .05). Lower GCS (OR: 0.66, 95% CI: 0.45-0.82; P = .001), lower admission oxygen saturation (OR: 0.82, 95% CI: 0.69-0.98; P = .025), and the development of systolic dysfunction (OR: 4.85, 95% CI: 1.36-17.22; P = .015) were independent risk factors for in-hospital mortality in patients with Ims-TBI. Heart rate, GCS, and serum Hs-cTnT level on admission were independent early risk factors for systolic dysfunction in patients with Ims-TBI. The combination of these 3 parameters can better predict the occurrence of systolic dysfunction.

Premature ventricular complexes: new possibilities of diagnostics and management

Premature ventricular complexes (PVC) is one of the most common arrhythmias in daily clinical practice. In the vast majority of cases, PVC has a good prognosis, but in some cases it can cause serious, including lifethreatening complications. On the other hand, asymptomatic, frequent PVC can lead to the development of left ventricular (LV) systolic dysfunction, which can be reversible with effective therapy. Medications remain the mainstay of therapy for PVC. However, the effectiveness of some drugs is quite low, while other drugs have significant side and proarrhythmic effects. Technological advances in the field of radiofrequency (RF) catheter ablation in recent years have opened up tremendous prospects in the radical correction of PVC and put forward this approach in selective cases as the method of choice. However, this invasive technology may at the same time carry the risks of serious complications, which can occur in up to 5% of individuals undergoing this procedure. The potential risks of RF catheter ablation largely depend on the accessibility of the ectopic focus. In this regard, differential diagnosis of the source of ectopia is of great importance for a balanced assessment of the possible risks and effectiveness of this invasive method. Standard diagnostic methods, such as 12-lead electrocardiography, Holter monitoring and echocardiography, allow in many cases to make the best decision regarding further management tactics. Frequent, asymptomatic PVC needs in annual monitoring to prevent LV systolic dysfunction development in cases high potential RF catheter ablation risks and drugs ineffectiveness. Traditional echocardiography and novel ultrasound technologies can help in this difficult of choice cases.

Efficacy and safety of CDR132L in patients with reduced left ventricular ejection fraction after myocardial infarction: Rationale and design of the HF-REVERT trial.

Inhibition of microRNA (miR)-132 effectively prevents and reverses adverse cardiac remodelling, making it an attractive heart failure (HF) target. CDR132L, a synthetic antisense oligonucleotide selectively blocking pathologically elevated miR-132, demonstrated beneficial effects on left ventricular (LV) structure and function in relevant preclinical models, and was safe and well tolerated in a Phase 1b study in stable chronic HF patients. Patients with acute myocardial infarction (MI) and subsequent LV dysfunction and remodelling have limited therapeutic options, and may profit from early CDR132L treatment. The HF-REVERT (Phase 2, multicenter, randomized, parallel, 3-arm, placebo-controlled Study to Assess Efficacy and Safety of CDR132L in Patients with Reduced Left Ventricular Ejection Fraction after Myocardial Infarction) evaluates the efficacy and safety of CDR132L in HF patients post-acute MI (n = 280), comparing the effect of 5 and 10 mg/kg CDR132L, administered as three single intravenous doses 28 days apart, in addition to standard of care. Key inclusion criteria are the diagnosis of acute MI, the development of systolic dysfunction (LV ejection fraction ≤45%) and elevated N-terminal pro-B-type natriuretic peptide. The study consists of a 6-month double-blinded treatment period with the primary endpoint LV end-systolic volume index and relevant secondary endpoints, followed by a 6-month open-label observation period. The HF-REVERT trial may underpin the concept of miR-132 inhibition to prevent or reverse cardiac remodelling in post-MI HF. The results will inform the design of subsequent outcome trials to test CDR132L in HF.

Complex Substrate Leading to PVC-Mediated Systolic Dysfunction in addition to Sustained Monomorphic VT in Repaired Tetralogy of Fallot.

Frequent premature ventricular complexes (PVCs) are associated with deleterious effects on left ventricular (LV) function in various clinical scenarios. Repaired tetralogy of Fallot (rTOF) is frequently affected by sustained ventricular arrhythmias dependent on complex post-surgical substrates. However, there is limited data regarding the potential of arrhythmogenic isthmuses to generate frequent PVCs and PVC-mediated LV systolic dysfunction development in rTOF. We present a case of rTOF experiencing relatively infrequent episodes of internal shocks for episodes of sustained monomorphic ventricular tachycardia and a high burden of PVCs associated with left ventricular systolic function deterioration, in which the successful substrate ablation of the anatomical VT isthmuses also led to PVC abolition and consequently to LV systolic function normalization. In such cases, understanding the pathogenic mechanisms that lead to LV dysfunction is only possible by rigorous clinical reasoning, which leads to a tailored specific treatment.

Thinning of compact layer and systolic dysfunction in isolated left ventricular non-compaction: A cardiac magnetic resonance study

BackgroundThe Petersen’ index reflects an excess of myocardial trabeculation which is not a specific morpho-functional feature of left ventricular non-compaction (LVNC) cardiomyopathy, but a “phenotypic trait” even observed in association with other myocardial diseases and over-loading conditions. The present study was designed to evaluate the relation between a critical thinning of compact layer and the development of systolic dysfunction and LVNC cardiomyopathy. MethodsWe compared CMR morpho-functional features and measurements of LV wall thickness using a 17 segment model of a cohort of patients fulfilling the Petersen criterion for LVNC with LV systolic dysfunction versus those of a cohort of age- and sex-matched controls with LVNC and preserved LV systolic function. All the study patients had an “isolated” LVNC defined as positive Petersen criterion in the absence of other diseases such as hypertrophic and dilated cardiomyopathy, valvular heart disease, or congenital heart disease and over-loading conditions. Resultshe study population included 33 patients with “isolated” LVNC: 11 consecutive index patients with a reduced LV ejection fraction (LVNCrEF) and 22 controls with a preserved LVEF (LVNCpEF). The compact myocardial layer was thinner in patients with LVNCrEF than in those with LVNCpEF patients, both in mid-ventricular and apical LV segments. On linear regression analysis, there was a linear correlation between median thickness of mid-ventricular free wall segments and left ventricular ejection fraction (r = 0.51, p = 0.005). On the ROC curves analysis, ≥2 segments with a compact myocardial layer <5 mm in the free wall mid-ventricular segments showed the best accuracy for reduced LVEF (100% sensitivity and 60% specificity; AUC 0.81, p < 0.01). The negative predictive value for LV systolic dysfunction of <2 free wall mid ventricular segments <5 mm was 100%. On quantitative analysis, the mass of papillary muscles was lower in patients with LVNCrEF [1.2 (0.8–1.4) versus 1.6 (1.1–1.8) g/mq; p = 0.08]. Conclusions: A thinned compact layer of mid-ventricular segments of the LV free wall was associated with a reduced systolic function and “isolated” LVNC cardiomyopathy.

Abstract 15115: Efficacy and Safety of miR-132 Inhibitor CDR132L in Patients With Reduced Left Ventricular Ejection Fraction After Myocardial Infarction: Rationale for and Design of the HF-REVERT Trial

Background: Inhibition of miR-132 effectively prevents and reverses heart failure (HF) in relevant models, making it an attractive HF target. CDR132L is a synthetic antisense oligonucleotide (ASO) selectively blocking miR-132. Translational in vitro and in vivo studies have demonstrated meaningful efficacy of CDR132L on left ventricular (LV) structure and function. CDR132L was safe and well tolerated in a Phase 1b study in chronic HF patients. The indicative effects of the miR-132 inhibitor CDR132L may be particularly beneficial in patients with active adverse remodelling, e.g. after acute myocardial infarction with early decline in ejection fraction. These patients have been relatively understudied and therapeutic options are limited. Method: The HF-REVERT (P h ase 2, Multicenter, Randomized, Parallel, 3-arm, Placebo-controlled Study to Assess E f ficacy and Safety of CD R 132L in Pati e nts with Reduced Left V entricular E jection F r ac t ion (≤ 45%) after Myocardial Infarction; NCT05350969) is a proof-of-concept study to evaluate the efficacy of CDR132L in improving cardiac function and safety in patients with reduced LV ejection fraction (LVEF). HF-REVERT aims to assess the efficacy and safety of 5 mg/kg and 10 mg/kg CDR132L, given as 3 single intravenous doses administered 28 days apart as an add-on to standard-of-care treatment, in a larger cohort of patients (N = 280) with HF and reduced LVEF (≤ 45%) after MI with a follow-up of 10 months. Key inclusion criteria are the diagnosis of acute STEMI/NSTEMI and the development of systolic dysfunction (LVEF ≤ 45%) after MI index event and elevated N-terminal pro B-type natriuretic peptide (NT-proBNP). The study consists of a 6-month double-blind treatment period with a read out of the primary endpoint LVESVI (left ventricular end systolic volume index) followed by a 6-month open label observation period. Discussion: The HF-REVERT trial currently tests CDR132L in patients with MI and systolic dysfunction. This trial may therefore underpin the concept of miR-132 inhibition to prevent/reverse cardiac remodeling in HF patients. The results will inform the design of a subsequent outcome trial to test the effect of CDR132L in HF patients.

Risk factors for the development of heart failure with a preserved left ventricular ejection fraction in workers of the main professions of the coal industry

Introduction. In the coal industry, 78.7% of employees work in places with harmful working conditions, which play a leading role in the development of not only professional, but also industrial diseases, the leading of which are diseases of the cardiovascular system. The identification of preclinical systolic dysfunction of the left ventricle and the assessment of the role of traditional and professionally determined risk factors for the development of systolic dysfunction of the left ventricle in workers of the main professions of the coal industry is of scientific interest.&#x0D; The study aims to assess the risk factors for the development of heart failure with a preserved left ventricular ejection fraction in workers of the main professions of the coal industry.&#x0D; Materials and methods. The study included 101 employees of the main professions of the coal industry and 80 employees of the paramilitary mine rescue unit. The subjects had no somatic pathology, which could lead to structural and functional changes of the heart. The scientists performed echocardiographic and ultrasound examinations of the main arteries according to standard methods and assessed the generally accepted risk factors for the development of cardiovascular pathology (smoking, abdominal obesity, body mass index, total cholesterol, triglycerides, high and low density lipoprotein cholesterol, glycated hemoglobin).&#x0D; Results. The researchers revealed systolic dysfunction of the left ventricle significantly in miners more often in the form of a decrease in longitudinal deformation (27.7% of miners versus 7.6% of paramilitary rescuers, p=0.0005), while its average value is also significantly lower in miners and has a value below the established norm (–17.2±0.044 and –19.3±0.03, p=0.0005). The authors found no significant differences in the frequency of commonly accepted risk factors: abdominal obesity, smoking, atherosclerosis of the main arteries, dyslipidemia and the level of glycated hemoglobin in miners and workers of the mine rescue unit, as well as in miners, depending on the index of longitudinal deformation of the left ventricle.&#x0D; Conclusion. The obtained results indicate the need for a prenosological diagnosis of systolic dysfunction of the left ventricle, studying it in dynamics and simultaneously expanding the search for risk factors, which will allow early prevention of this complication in workers in harmful working conditions.&#x0D; Ethics. The study was conducted in compliance with the standards of the Bioethical Committee of the Research Institute of Complex Problems of Hygiene and Occupational Diseases, established in accordance with the Helsinki Declaration of the World Association "Ethical Principles of Scientific Medical Research with Human Participation" as amended in 2013 and the "Rules of Good Clinical Practice" approved by Order of the Ministry of Health of the Russian Federation dated 01.04.2016 No. 200n. The subjects signed an informed consent to participate in the study.

IL-1β is not critical to chronic heart dysfunction in mice with Chagas disease.

Long after Trypanosoma cruzi infection, 40% of individuals develop a progressive chronic chagasic cardiomyopathy (CCC), with systolic dysfunction and arrhythmias. Since we previously showed IL-1β mediates the development of systolic dysfunction and cardiac arrhythmias in diabetes mellitus and cardiorenal syndrome, and IL-1β remains elevated in Chagas disease patients, here we tested the role of IL-1β in CCC using a mouse model. Mice deficient in IL-1R expression (Il-1r-/- ) survived acute T. cruzi infection with greater parasitemia than controls but did not lose weight as wild-type (WT) did. At the chronic stage, WT presented prolonged ventricular repolarization intervals (QJ), while Il-1r-/- presented intervals like noninfected controls. Infected Il-1r-/- and WT did not differ in stroke volume (SV), the incidence of cardiac arrhythmias on electrocardiography (EKG), whole heart action potential duration (APD), or the incidence of triggered activity after S1-S2 protocol, which is a measure of susceptibility to cardiac arrhythmias. We also treated chronically infected WT mice with an IL-1R antagonist, anakinra. Treatment shortened the QJ interval but did not improve the SV or the incidence of cardiac arrhythmias on EKG. Anakinra failed to reduce triggered activity following the electrical extra-stimulation protocol. In conclusion, the absence of functional IL-1β/IL-1R signaling did not prevent or reverse the decrease of SV or the incidence of cardiac arrhythmias induced by chronic T. cruzi infection, implying this is not a critical mechanism in generating or maintaining CCC. Since similar cardiac abnormalities were previously credited to IL-1β signaling, ruling out this mechanism is important to discourage further attempts of IL-1β blockade as a therapeutical measure.

Non-specific intraventricular conduction delay or atypical LBBB - How to predict acute coronary occlusion?

We describe two patient cases with acute coronary syndrome (ACS) and broad QRS in the acute phase electrocardiogram (ECG). The patients' ECG findings resembled left bundle branch block (LBBB), but with atypical features. Broad QRS not fulfilling the criteria for LBBB or right bundle branch block (RBBB) is diagnosed as non-specific intraventricular conduction delay (NSIVCD). The case report deals with the challenges of predicting acute coronary occlusion in patients with NSIVCD in their acute phase ECG. In one of the cases, the ECG changed from typical LBBB to NSIVCD or atypical LBBB with the development of systolic dysfunction and clinical heart failure.

Comparison of the effect of three steroid regimens on cardiac function in Duchenne muscular dystrophy

BackgroundSteroid therapy of patients with Duchenne muscular dystrophy (DMD) delays the onset of cardiac dysfunction. ObjectiveThe aim of this study was to compare the effects of 3 different steroid regimens on cardiac function assessed by echocardiography. MethodsPatients diagnosed with DMD, between 8 and 23 years of age were reviewed between January 2000 and September 2018. Participants were classified into four groups. Control group (no steroid treatment), Prednisone 10 mg/kg/weekend day, Prednisone 0.40 mg - 0.75 mg/kg/day and Deflazacort 0.9 mg/kg/day.Demographic data, echocardiographic measurements of shortening fraction (FS) and left ventricular end diastolic diameter z-score were collected and compared between cohorts. ResultsDevelopment of cardiac dysfunction in groups receiving prednisone daily or 3 day prednisone was less common in comparison to the control group (p = 0.005). No patient on the Deflazacort group had abnormal left ventricular FS. There was no difference in the age of initiation of steroid therapy among groups (p = 0.08). Age of development of systolic dysfunction by echocardiography between daily prednisone and weekend prednisone was not significantly different (p = 0.07). There was no difference in the number of patients developing of cardiac dysfunction between patients receiving prednisone daily or 3 day prednisone (p = 0.4). The entire cohort (77 patients) demonstrated a decline in the cardiac function over time. ConclusionsOur study confirms the delay in development of left ventricular dysfunction related to steroid therapy. Deflazacort seems to show a significant beneficial effect on cardiac function, compared to daily and weekend prednisone therapies.

PAK3 overexpression during stress-induced cardiac hypertrophy dysregulates autophagy augmenting acute cell death and accelerating the development of systolic dysfunction

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): British Heart Foundation Introduction The understanding of stress-induced cardiac hypertrophy remains vital for preventing and better treatment of heart failure. Studies of the p-21activated kinase (PAK) family describe the cardioprotective roles of PAK1 and PAK2 proteins; however, the function of PAK3 is not known. Unlike the first two, the expression of PAK3 increases in failing hearts, suggesting it has distinct regulatory pathways and functions. Purpose Elucidate the role of PAK3 during the cardiac stress response and its contribution to the development of cardiac hypertrophy and dysfunction. Methods A cardiac-specific PAK3 overexpression mouse model was established by administering an AAV9 vector carrying a PAK3 coding sequence regulated by the Troponin promoter. Acute cardiac stress consisted of two consecutive isoprenaline injections, while the long-term experiment employed subcutaneous minipumps for constant release over two weeks. Cardiac function was assessed by echocardiography, cardiac morphology through histological staining, and protein expression by western blot. For the in vitro experiments, an adenoviral vector was used for overexpression on neonatal rat ventricular myocytes, and starvation was used to induce stress. The tandem mCherry-Gfp-LC3 reporter was used to detect autophagic flux by immunofluorescence and flow cytometry. Cell death was evaluated by measuring lactate dehydrogenase release (LDH) and using the Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL) assay. Results After only two days of isoprenaline-induced stress, cardiac PAK3 overexpression in mice resulted in a reduced fractional shortening and enlarged ventricular chamber diameter. Histological analysis showed a rise in interstitial fibrosis and apoptotic cardiomyocytes. Increasing the exposure time to cardiac stress to two weeks aggravated the alterations detected in the acute model. Western blot revealed an mTOR overactivation, possibly through the disassembly of the TSC1 complex, accompanied by the alteration of autophagic markers. In vitro experiments confirmed that PAK3 overexpression led to basal mTOR and autophagosome formation activation but with an impaired flux. One hour of starvation induced LDH release and cardiomyocyte apoptosis, worsened by PAK3 overexpression. These effects were recovered by the MTOR-independent autophagy inducer ABT-737 in vitro and by the recently produced MSL-7. Conclusion Contrary to the proteins in the family, PAK3 overexpression is damaging for cardiac function. It dysregulates the autophagic process and renders the cardiomyocytes unable to sustain acute stress. The administration of the autophagy inducer MSL-7 improved muscle tolerance to stress and preserved function showing its therapeutic properties in stress-induced cardiac hypertrophy. The rapidity with which PAK3 overexpression induced systolic dysfunction portrays the importance of further studying its function in cardiac health and disease.

Contribution of Global and Regional Longitudinal Strain for Clinical Assessment of HFpEF in Coronary and Hypertensive Patients.

Background: Contribution of global and regional longitudinal strain (GLS) for clinical assessment of patients with heart failure with preserved ejection fraction (HFpEF) is not well established. We sought to evaluate subclinical left ventricular dysfunction secondary to coronary artery disease (CAD) in HFpEF patients compared with hypertensive patients and age-matched healthy subjects. Material and methods: This was a retrospective study that included 148 patients (group 1 = 62 patients with HFpEF, group 2 = 46 hypertensive patients, and group 3 = 40 age-matched control subjects). Peak systolic segmental, regional (basal, mid, and apical), and global longitudinal strain were assessed for each study group using two-dimensional speckle-tracking echocardiography (2D-STE). Results: GLS values presented statistically significant differences between the three groups (p < 0.001); markedly increased values (more negative) were observed in the control group (−20.2 ± 1.4%) compared with HTN group values (−18.4 ± 3.0%, p = 0.031) and with HFpEF group values (−17.6 ± 2.3%, p < 0.001). The correlation between GLS values and HTN stages was significant, direct, and average (Spearman coefficient rho = 0.423, p < 0.001). GLS had the greatest ability to detect patients with HFpEF when HFpEF + CAD + HTN diastolic dysfunction (n = 30) + CON diastolic dysfunction (n = 2) from HFpEF + CAD + HTN + CON was analyzed. (optimal GLS limit of −19.35%, area under curve = 0.833, p < 0.001). Conclusions: Global longitudinal strain can be used for clinical assessment in differentiating coronary and hypertensive patients at higher risk for development of systolic dysfunction.

Systolic Dysfunction of the Heart in Type 1 Diabetes Mellitus.

Impaired insulin synthesis is accompanied by hyperglycemia and the development of diabetic cardiomyopathy. Echocardiography and left-ventricular catheterization were employed for studying the contractile function of the left ventricle in 2 weeks after administration of streptozotocin (60 mg/kg). The results obtained by both methods were similar and indicated the development of systolic dysfunction with a 27% decrease in cardiac output. The invasive study showed that the maximum rate of left-ventricular pressure development, the contractility index, and systolic left-ventricular pressure were within the normal range, but the peak ejection rate was reduced by 28%. BP was normal, but the vascular stiffness index was increased by about 1.5 times and inversely correlated with the peak ejection rate (r=-0.69). The results showed that systolic dysfunction in type 1 diabetes model was due to reduced ejection from the left ventricle at normal rate of left-ventricular pressure development.

Abstract P121: Combining Extracellular Matrix Biomarkers Using Cluster Analysis More Accurately Predicts The Development Of Systolic Dysfunction In Acute Myocardial Infarction Compared To Single Biomarker Analysis

Introduction: The extracellular matrix (ECM) is central to cardiac repair following acute myocardial infarction (AMI), and pathological ECM activity may result in adverse ventricular remodeling. Systolic dysfunction is a manifestation of adverse remodeling, and the utility of combined biomarker analysis for prognosis remains undetermined. Cluster analysis is a statistical methodology that can combine biomarkers, while also accounting for collinearity. Hypothesis: In this study, we assessed the hypothesis that combining biomarkers using cluster analysis may more accurately predict the development of systolic dysfunction in AMI patients when compared to single biomarker analysis. Methods: In a cohort of 120 AMI patients, plasma levels of matrix metalloproteinase (MMP) -3, -8, -9 and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) were measured using ELISA and multiplexing assays during hospital admission. All patients had an echocardiogram within 1 year of AMI (median [IQR], 145 [89 - 252] days). Patients were divided into impaired (n=37, LVEF &lt;50%) and preserved (n=83, LVEF ≥50%) systolic function. Hierarchical clustering was performed using Ward’s method of minimum variance. Mann-Whitney U and Chi-Squared testing was performed for univariate analysis, and binary logistic regression was performed for multivariate analysis. Results: Upon univariate analysis, current smoking, prescription of ACE inhibitor at discharge, peak Troponin T &gt; 610 ng/L (median), and MMP-8 levels were predictive of impaired systolic function. Cluster analysis partitioned patients into two clusters (Cluster One, n=31; Cluster Two, n=89). Cluster One comprised a higher proportion of patients with impaired systolic function when compared to Cluster Two (15 out of 31 [48.4%] versus 22 out of 89 [24.7%]). Upon multivariate analysis, Cluster One assignment (odds ratio [95% CI], 2.74 [1.04-7.23], p=0.04) remained an independent predictor of systolic dysfunction in combination with clinical variables, while MMP-8 levels did not (3.43 [0.32-36.68], p=0.308). Conclusion: Findings from our study demonstrate a combined biomarker approach outperforms single biomarker analysis for predicting the development of systolic dysfunction following AMI.

Usefulness of Global Longitudinal Strain to Predict Heart Failure Progression in Patients With Nonobstructive Hypertrophic Cardiomyopathy

While predicting prognosis to anticipate adverse disease course has long been an aspiration in hypertrophic cardiomyopathy (HC), reliable markers of progressive and unrelenting heart failure symptoms in the absence of obstruction are not well characterized. We sought to evaluate markers of systolic function, including the role of global longitudinal strain (GLS), to identify nonobstructive HC patients at risk for future heart failure. A cohort of 296 consecutive nonobstructive HC patients (42 ± 18years; 75% male) with NYHA class I/II symptoms and preserved systolic function at study entry (EF: 65 ± 6%), were followed for progressive heart failure symptoms (increase in ≥ 1 NYHA functional class) and/or development of systolic dysfunction (EF < 50%). Over median follow-up of 4 ± 3 years, 35 study patients (10%) experienced new heart failure events, including 31 with progressive symptoms and 4 who developed systolic dysfunction. Abnormal GLS < 16% was associated with a 5-fold increase in risk for heart failure compared to GLS > 18% (p < 0.001). GLS remained an independent predictor of heart failure even after adjustment for other relevant disease variables including EF (OR 1.23, p = 0.005). However, notably, when GLS and EF were combined, the prediction of heart failure for individual patients was enhanced (net reclassification improvement 0.55; p = 0.002). Together, GLS < 16% and EF 50% to 59% were associated with a 12.5-fold greater risk for heart failure versus patients with GLS > 18% and EF ≥ 60%, who were at the lowest risk. In conclusion, in nonobstructive HC with no or mild symptoms and preserved EF, abnormal GLS is a strong independent predictor for subsequent development of progressive heart failure symptoms and/or systolic dysfunction. Furthermore, the greatest power in predicting outcome in nonobstructive HC is achieved by combining GLS with EF to identify HC patients at the highest risk for heart failure progression and systolic dysfunction.

Doppler examination of aorta after therapeutic hypothermia and administering MSCs in experimental myocardial infarction

Background. At present, there are attempts aimed at repairing the myocardium affected by acute myocardial infarction (MI) via biologically sourced drugs, which are able to stimulate reparative regeneration, including the use of mesenchymal stromal cells (MSCs). On the other hand, therapeutic hypothermia initially after the occurrence of impaired blood flow in the coronary arteries aids in reducing the level of metabolism in cardiomyocytes and, accordingly, suppressing the formation of free radicals and inhibiting apoptosis.&#x0D; Purpose – рerforming and analysing Doppler sonography of the ascending aorta in rats with experimental MI in order to assess the systolic function of the left ventricular myocardium influenced by the combined use of therapeutic hypothermia and administering allogeneic MSCs.&#x0D; Materials and methods. The study involved 90 outbred white rats weighing 240–270 g. Myocardial infarction was reproduced by ligating the left coronary artery. Therapeutic hypothermia was performed in a cold chamber, 60 minutes long. The local skin temperature of the neck area was maintained at +4 оС. A suspension of allogeneic cryopreserved MSCs of the placenta was administered once intravenously. Sonography of the ascending aorta on day 7 and day 30 after ligating the coronary artery was carried out by means of «Сономед 500» ultrasound scanner in B-mode with the Doppler (PW-mode).&#x0D; Results. Studying the aortic blood flow showed that on day 7 after ligating the coronary artery, rats had a decrease in max systolic velocity and a tendency to increase diastolic blood flow velocity. Those changes influenced the pulsatility index and systolic-diastolic ratio. A 19 % decrease in the Stewart index confirmed the development of systolic dysfunction in the control group, the severity of which did not decrease until day 30 of the experiment. The impact of allogeneic MSCs on the process of remodeling the heart of rats after ligating the left coronary artery was evident on day 7 (acute stage of myocardial infarction) via abnormally low (below control) blood flow in the aorta with complete hemodynamics restoring on day 30 of the experiment. The combination of therapeutic hypothermia and administering allogeneic MSCs aided in the minimal deviation of hemodynamic parameters from the normal range. On day 7, there was only an increase in the average aortic blood flow rate by 29%, and a decrease in systolic-diastolic ratio by 12% compared to the corresponding normal range, suggesting compensation of the pumping function of the myocardium.&#x0D; Conclusions. Doppler assessment of systolic and diastolic blood flow velocities in the ascending aorta of rats makes it possible to indirectly record the presence and severity of systolic dysfunction of the left ventricle and follow up myocardial contractile function affected by MI. The combination of therapeutic hypothermia and administering allogeneic MSCs after ligating the left coronary artery helps to maintain hemodynamic parameters in the aorta at a level close to normal range during the acute phase of myocardial infarction as well as at the stage of scarring.

Diastolic function as an early marker for systolic dysfunction and all-cause mortality among cancer patients.

Increased survival among active cancer patients exposes a wide range of side effects, including cardiotoxicity, manifested by systolic dysfunction and associated with morbidity and mortality. Early diagnosis of subclinical function changes and cardiac damage is essential in the management of these patients. Diastolic dysfunction is considered common among cancer patients; however, its effect on systolic dysfunction or mortality is still unknown. Data were collected as part of the Israel Cardio-Oncology Registry, enrolling and prospectively following all patients evaluated in the cardio-oncology clinic in the Tel Aviv Sourasky Medical Center. All patients underwent echocardiographic examinations including evaluation of diastolic parameters and global longitudinal strain (GLS). Systolic dysfunction was defined as either an absolute reduction >10% in left ventricular ejection fraction to a value below 53% or GLS relative reduction >10% between the 1st and 3rd echocardiography examinations. Overall, 190 active cancer patients were included, with a mean age of 58±15years and a female predominance (78%). During a median follow-up of 243days (interquartile ranges [IQR]: 164-401days), 62 (33%) patients developed systolic dysfunction. Over a median follow-up of 789days (IQR: 521-968days), 29 (15%) patients died. There were no significant differences in baseline cardiac risk factors between the groups. Using multivariate analysis, E/e' lateral and e' lateral emerged as significantly associated with systolic dysfunction development and all-cause mortality (P=.015). Among active cancer patients, evaluation of diastolic function may provide an early marker for the development of systolic dysfunction, as well as all-cause mortality.

A Novel ALDH2 Activator AD-9308 Improves Diastolic and Systolic Myocardial Functions in Streptozotocin-Induced Diabetic Mice

Diabetes mellitus has reached epidemic proportion worldwide. One of the diabetic complications is cardiomyopathy, characterized by early left ventricular (LV) diastolic dysfunction, followed by development of systolic dysfunction and ventricular dilation at a late stage. The pathogenesis is multifactorial, and there is no effective treatment yet. In recent years, 4-hydroxy-2-nonenal (4-HNE), a toxic aldehyde generated from lipid peroxidation, is implicated in the pathogenesis of cardiovascular diseases. Its high bioreactivity toward proteins results in cellular damage. Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is the major enzyme that detoxifies 4-HNE. The development of small-molecule ALDH2 activator provides an opportunity for treating diabetic cardiomyopathy. This study found that AD-9308, a water-soluble andhighly selective ALDH2 activator, can improve LV diastolic and systolic functions, and wall remodeling in streptozotocin-induced diabetic mice. AD-9308 treatment dose-dependently lowered serum 4-HNE levels and 4-HNE protein adducts in cardiac tissue from diabetic mice, accompanied with ameliorated myocardial fibrosis, inflammation, and apoptosis. Improvements of mitochondrial functions, sarco/endoplasmic reticulumcalcium handling and autophagy regulation were also observed in diabetic mice with AD-9308 treatment. In conclusion, ADLH2 activation effectively ameliorated diabetic cardiomyopathy, which may be mediated through detoxification of 4-HNE. Our findings highlighted the therapeutic potential of ALDH2 activation for treating diabetic cardiomyopathy.

Systolic left ventricular dysfunction in patients with clinically suspected myocarditis

The aim of the study was to investigate the features of clinically suspected myocarditis complicated by the left ventricular systolic dysfunction development. 93 patients with clinically suspected myocarditis were examined. The average age was 36.63 ± 1.15 years. In 43.01 % of patients the disease was accompanied by a decrease in left ventricular systolic function. In the group of patients with left ventricular systolic dysfunction in comparison with those with preserved left ventricular ejection fraction, a significantly lower proportion of men (75 % versus 81 %, respectively, χ2 = 9.3, p &lt; 0,01) and a higher average group age (40.7 ± 1.87 versus 33.6 ± 1.3 years, respectively, p &lt; 0,01) were revealed. The course of the disease in patients with left ventricular systolic dysfunction was characterized by a more frequent development of rhythm disturbances (65 % versus 43.3 %, respectively, χ2 = 4.3, p &lt; 0,05) and a higher heart rate at admission (94.5 (75‒100) and 85 (70‒89) beats per minute, respectively, p = 0.006). The structural and functional state of the heart according to echocardiography in patients with a reduced left ventricular ejection fraction versus comparison group was characterized by larger heart chambers sizes, more pronounced violations of local left ventricular contractility, more frequent involvement of the right ventricle in the pathological process (56.3 % versus 22.2 %, respectively, χ2 = 6.4, p &lt; 0,05). The relationships between the left ventricular ejection fraction Весці Нацыянальнай акадэміі навук Беларусі. Серыя медыцынскіх навук. 2020. Т. 17, № 4. C. 452–460 453 and the patient’s age (r = ‒0.36), the value of the heart rate at admission (r = ‒0.32), the severity of heart failure at admission, the degree of impaired local contractility of the left ventricle, the degree of right ventricular function (TAPSE, r = 0.58), the severity of myocardial fibrosis according to cardiovascular magnetic resonance imaging (r = ‒0.32) were revealed.

Longitudinal diastolic strain slope as an early sign for systolic dysfunction among patients with active cancer.

Diastolic dysfunction is a common finding in patients receiving cancer therapy. This study evaluated the correlation of diastolic strain slope (Dss) with routine echocardiography diastolic parameters and its role in early detection of systolic dysfunction and cardiovascular (CV) mortality within this population. Data were collected from the Israel Cardio-Oncology Registry (ICOR), a prospective registry enrolling adult patient receiving cancer therapy. All patients performed at least three echocardiography exams (T1, T2, T3), including left ventricle Global Longitudinal Strain (LV GLS) and Dss. Systolic dysfunction was determined by either LV GLS relative reduction of ≥ 15% or LV ejection fraction reduction > 10% to < 53%. Dss was assessed as the early lengthening rate, measured by the diastolic slope (delta%/sec). Among 144 patients, 114(79.2%) were female with a mean age of57.31 ± 14.3years. Dss was significantly correlated with e' average. Mid segment Dss change between T1 and T2 showed significant association to systolic dysfunction development (Odds Ratio (OR) = 1.04 [1.01,1.06]. p = 0.036). In multivariate prediction, Dss increase was a significant predictor for the development of systolic dysfunction (OR = 1.06 [1.03,1.1], P < 0.001).An 8% increase in Dss between T1 and T2 was associated with a trend in increased CV mortality (HR = 3.4 [0.77,15.4], p = 0.085). This study is the first to use the novel measurement of Dss in patients treated with cancer therapies and to show significant correlation between routine diastolic dysfunction parameters and Dss. Changes in the mid segment were found to have significant independent early predictive value for systolic dysfunction development in univariate and multivariate analyses.