Contractile Function Of Left Ventricle Research Articles

Left Ventricular Remodeling after Percutaneous Coronary Intervention in Acute Myocardial Infarction Complicated by Acute Heart Failure

The aim. To establish the relationship between structural-functional and laboratory parameters in patients with myocardial infarction (MI) and heart failure (HF) undergoing percutaneous coronary intervention (PCI). Materials and methods. We examined 308 MI patients who were divided into 3 groups: 161 patients without signs of acute heart failure (AHF) (group I), 99 with Killip class II-III AHF (group II) and 48 with Killip class IV (cardiogenic shock) (group III). All the patients underwent general clinical examinations: complete blood count, lipid profile, creati-nine, quantitative determination of troponin I, D-dimer, creatine kinase-MB, electrocardiography, coronary angiography with PCI, focused cardiac ultrasound and standard echocardiography over 3-5 days. Results. According to the focused cardiac ultrasound, the majority of MI patients with signs of AHF had preserved left ventricle function, and only 8.2% of patients had left ventricle ejection fraction (LVEF) ˂40%. The most significant structural and functional changes were observed in group II. After PCI, a significant increase in left ventricle contractility was found in all groups, but in the group II, the increase in LVEF was more pronounced. The severity of HF manifestations increased depending on the severity of diastolic dysfunction. Many correlations were established: an inverse relationship between LVEF and the presence of HF, the number ofaffected vessels, proximal left anterior descending artery lesions, low-density lipoprotein cholesterol, and atrium fibrilla-tion; a direct relationship between LVEF and hemoglobin levels and glomerular filtration rate. Conclusions. The vast majority of patients with MI and signs of AHF had preserved left ventricle contractile function. High-grade HF manifestations increase depending on the severity of diastolic dysfunction. Myocardial revascularization in MI pa-tients significantly improves functional and volumetric parameters of myocardial function. Numerous correlations between structural-functional and laboratory parameters in patients with MI and HF who underwent PCI have been established.

LV systolic function assessment in conventional cardiac pacing: a simple and forgotten parameter - MAPSE

Abstract Background Mitral annular plane systolic excursion (MAPSE) was a widely used M-mode echocardiographic marker of left ventricular longitudinal systolic function. On the other hand, right ventricle (RV) apical pacing is associated with left ventricle (LV) dysfunction development due to dysynchronous activation, while non-apical pacing may provide a more physiological LV activation. The aim of this study is to ascertain the clinical usefulness of MAPSE in the assessment of LV contractile function in patients with permanent RV pacing. Methods Consecutive patients with indication for permanent cardiac pacing (with ventricular pacing percentages over 20% - Vp>20%) were retrospectively enrolled from 2019 to 2023. All patients were assessed by echocardiography with MAPSE, left ventricule ejection fraction (LVEF) and diastolic filling patterns being measured at the time of implant and at subsequent follow-ups. Results 359 patients (age range 41-80yo; mean age=60,5yo) were included, 244 men and 115 women, 173 implanted with single-chamber devices and 186 dual-chamber. 259 patients were paced from the RVA (right ventricle apex) and 62 had septal lead positioning. The mean follow-up period was 18±2 months. The results showed that a MAPSE cut off value of ≤10 mm was associated with a LVEF<42±2%, while MAPSE values >10mm were associated with LVEF>45±3% (p<0.01). RV septal pacing was associated with a higher average MAPSE value (14,28 mm) than RVA pacing (13,47). Conclusions MAPSE seems to corelate well with LVEF in RV conventional pacing. Younger patients with preserved LVEF and less than grade II diastolic dysfunction were not associated with a significant decrese in MAPSE value. However, older patients with HFmrEF and RVA pacing seem to have a more substantial reduction in MAPSE value, suggesting that non-apical or conduction system pacing might be beneficial in this subgroup. MAPSE seems to be a quick and reliable echocardiographic marker of LV systolic function in patients with permanent cardiac pacing. It may be used as an early predictive marker for heart failure in conventional RV paced patients.

Peculiarities of the ST-segment elevation myocardial infarction morphogenesis after mechanical restoration of epicardial blood flow without ECG signs of reperfusion

The aim of the study was to investigate the peculiarities of STEMI morphogenesis after mechanical restoration of epicardial blood flow without ECG signs of reperfusion. The autopsy data of 44 patients with STEMI who died at different times after PCI performed within the first 12 hours (27 cases), or 12–24 hours (17 cases), without ECG signs of reperfusion after the intervention, were analyzed. The comparison group consisted of 85 deceased without reperfusion therapy (RT). Histological examination of the myocardium was performed at following time: within 12 hours, at 13–24 hours, 2–4 days, 5–8 days, 9–15 and 16–22 days. The most common cause of death was acute left ventricular failure (ALVF) both in the group of blood flow restoration without ECG signs of reperfusion, and in the group without RT: 85 % and 79 %, respectively. In each of the two groups the number of deaths occurred in the first 12 hours exceeded one third, half of the patients died in the subsequent 12 hours, two thirds of the deaths occurred within further 2–3 days. The rates of risk factors: older age, anterior and recurrent myocardial infarction, three-vessel lesion of the coronary artery, and a large infarction area were similar in the two groups. From the first hours after PCI, the infarction zone was characterized by hemorrhagic imbibition, numerous injuries of the microcirculatory bed, by the signs of blood flow restoration in damaged vessels appeared from days 2–4, early manifestations of repair from days 5–7. In the MI group without PCI, the hemorrhagic demarcation started on days from 3–4, coagulation necrosis prevailed in the microvascular bed, signs of repair appeared at a later date. Multiple spasms and thromboses in the microvasculature may have been a response to a blood pressure drop that accompanies an acute decrease in the left ventricle contractile function caused by a large infarction area and/or unresolved complications arising during the interventions per se. This mechanism explains the rapid progression of left ventricular failure, the most common cause of death after the interventions with achieving the epicardial blood flow without ECG signs of reperfusion. The revealed microcirculation disorders reflect the absence of myocardial reperfusion, which is more prognostically significant than the restoration of epicardial blood flow.

The role of speckle-tracking echocardiography in the heart contraction geometry assessing in combatants with acute myocarditis

The aim – to evaluate the geometry of heart contraction based on speckle-tracking echocardiography data in combatants with acute myocarditis with reduced and mildly reduced left ventricular ejection fraction.Materials and methods. 53 male combatants with acute myocarditis (AM) were examined, who were divided into 2 groups: 1st group – 30 patients with a reduced ejection fraction (EF) of the left ventricle (LV) ≤ 40 %; 2nd group – 23 patients with mildly reduced LVEF 41–49 %. The diagnosis of AM was established on the basis of the recommendations for the diagnosis and treatment of myocarditis of the All-Ukrainian Association of Cardiologists of Ukraine. All patients underwent echocardiography (EchoCG) with speckle tracking (ST) and cardiac magnetic resonance (CMR) imaging with contrast.Results and discussion. Patients of the 1st group, compared to the 2nd, were characterized by more pronounced manifestations of dilatation and more significant violation of the LV contractile function, which was evidenced by a 13.6 % higher value of the LV end-diastolic volume and a 25.4 % smaller value of the LVEF. When evaluating ST echocardiographic indicators, the value of the longitudinal global systolic strain (LGSS) of the LV in the 1st group was 43.1 % lower, its velocity by 19.2 %, and the circular systolic deformation by 20.9 % in comparison with those in the 2nd group. In addition, in the 1st group, in comparison with the 2nd, the value of the indicator of systolic deformation of the left atrium (SDLA) was almost twice smaller. According to the results of CMR, in the 1st group compared to the 2nd, a larger number of segments with the presence of delayed enhancement was determined, which indicated a larger volume of fibrotic/necrotic lesions of the LV. According to the results of the correlation analysis in the 1st group, strong reverse relationships were established between the presence of delayed contrast in ≥ 4 segments of the LV and LGSS (r=–0.76; p<0.01), its speed and (r=–0.71; p<0.02) and SDLA (r=–0.52; p<0.05).Conclusions. Patients with acute myocarditis with a reduced left ventricular ejection fraction compared to patients with a mildly reduced ejection fraction were characterized by a greater violation of the geometry of the contraction of the left ventricle, which was observed on the background of a larger volume of fibrotic/necrotic lesions. With the help of correlation analysis, in combatants with acute myocarditis, a relationship was established between the presence of delayed enhancement in ≥ 4 segments of the left ventricle and a decrease in indicators of longitudinal systolic deformation and its speed, as well as an indicator of systolic deformation of the left atrium.

Impact of Impella protected-percutaneous coronary intervention on left ventricle function recovery of patients with extensive coronary disease and poor left ventricular function

BackgroundThe use of Impella support is increasingly adopted to “protect” patients with severe coronary artery disease (CAD) and left ventricle (LV) dysfunction undergoing percutaneous coronary intervention (PCI). AimsTo evaluate the impact of Impella-protected (Abiomed, Danvers, Massachusetts, USA) PCIs on myocardial function recovery. MethodsPatients with significant LV dysfunction undergoing multi-vessel PCIs with pre-intervention Impella implantation were evaluated by echocardiography before PCI and at median follow up of 6 months: global and segmental LV contractile function were assessed by LV ejection fraction (LVEF) and wall motion score index (WMSI), respectively. Extent of revascularization was graded using the British Cardiovascular Intervention Society Jeopardy score (BCIS-JS). Study endpoints were LVEF and WMSI improvement, and its correlation with revascularization. ResultsA total of 48 high surgical risk (mean EuroSCORE II 8) patients with median LVEF value of 30%, extensive wall motion abnormalities (median WMSI 2.16), and severe multi-vessel CAD (mean SYNTAX score 35) were included. PCIs brought a significant reduction of ischemic myocardium burden with BCIS-JS decrease from mean value of 12 to 4 (p < 0.001). At follow-up, WMSI reduced from 2.2 to 2.0 (p = 0.004) and LVEF increased from 30% to 35% (p = 0.016). WMSI improvement was proportional to the baseline impairment (R − 0.50, p < 0.001), and confined to revascularized segments (from 2.1 to 1.9, p < 0.001). ConclusionsIn patients with extensive CAD and severe LV dysfunction, multi-vessel Impella-protected PCI was associated to an appreciable contractile recovery, mainly determined by regional wall motion improvement in revascularized segments.

Influence of prosthesis – patient mismatch on long-term results in patients after aortic valve replacement with a biological prosthesis: retrospective single center study

Background. Despite numerous studies, ambiguity remains at present regarding the impact of prosthesis-patient mismatch (PPM) on long-term outcomes after aortic valve (AV) replacement.&#x0D; Objective. This study evaluates the effect of PPM on long-term results in patients after AV replacement with a biological prosthesis.&#x0D; Material and methods. We retrospectively analyzed the data of 231 patients who underwent AV replacement with a biological prosthesis from 2010 to 2018 at the Penza Federal Center of Cardiovascular Surgery. Patients were implanted with the following biological prostheses: Medtronic Mosaic, Edwards PERIMOUNT, Biocor.&#x0D; Results. Moderate PPM was present in 131 patients (56%), and severe PPM in 1 patient (0.7%). The mean follow-up was 78.832 months. There were no significant differences in hospital mortality in patients with and without PPM, 4 (3%) and 3 (2,9%), respectively, p=0.9. In the long-term period, patients with PPM showed a slower regression of left ventricle (LV) mass and recovery of LV contractile function than patients without PPM, p=0.05. There was no significant difference in survival in the long-term follow-up period between patients with and without PPM long-term survival, 77.7% and 79%, respectively, p=0.6. Also, there were no significant differences in major adverse cardiac events and the freedom from adverse events was 90% and 91%; p=0.7. However, there was a tendency to more frequent hospitalization for chronic heart failure (CHF) exacerbation in the patient group with PPM than in those without PPM, 63.8% and 78%; HR 1.6; 95% CI 0.932.1, p=0.007. There was also a tendency for an increased biological valve structural degeneration in the group with PPM than in the group without PPM 76% and 87%, HR 1.4; 95% CI 1.43.1, p=0.01 According to the Cox regression, the overall postoperative mortality predictors were diabetes mellitus, vascular atherosclerosis HR 5; 95% CI 1.222, p=0.04 and HR 2.9; 95% CI 1.46.6, p=0.01 respectively. Predictors of the risk of hospitalization due to CHF exacerbation were previous myocardial infarction and PPM HR 0.4; 95% CI 0.20.9, p=0.04 and HR 1,5; 95% CI 0.92; p=0.005, respectively PPM HR 2; 95% CI 0.854.1, p=0.01.&#x0D; Conclusion. PPM is a common complication after AV replacement with a biological prosthesis. It is associated with a slower regression of LV mass, an increased risk of structural valve degeneration, and hospitalizations for exacerbated heart failure.

The effectiveness of cardiac contractility modulation in patients with chronic heart failure and atrial fibrillation: results of the 12-month follow-up

To evaluate the efficacy, safety and effect on the prognosis of cardiac contractility modulation (CCM) in patients with chronic heart failure (CHF) with reduced left ventricular ejection fraction and atrial fibrillation compared with the group of only optimal drug therapy (ODT) of the 12-month follow-up. Patients (n=200) were sequentially included in two groups: group 1 patients with CHF who are on ODT in combination with implanted CCM devices (n=100), group 2 comparison patients with CHF who receive only ODT (n=100). Initially and after 12 months, 12-channel electrocardiography (ECG), transthoracic echocardiography, daily ECG-monitoring, determination of the level of NT-proBNP, a six-minute walk test and an assessment of the quality of life according to the Minnesota Questionnaire were performed. In the CCM therapy group, a significant clinical improvement was revealed, which was expressed in the form of a decrease in functional class CHF by NYHA (New York Heart Association), an increase in the distance of a six-minute walk test and an improvement in the quality of life according to Minnesota Questionnaire, as well as an improvement in left ventricle contractile function compared to the ODT group. The absence of a proarrhythmogenic effect of the CCM was shown. There was a significant decrease in the frequency of the readmission due to CHF and the probability of achieving the combined endpoint in the CCM therapy group compared with only ODT. The use of CCM in patients with CHF and atrial fibrillation is an effective and safe method of therapy that leads to the development of reverse remodeling of the myocardium, improves the clinical status of patients and reduces the frequency of readmission due to decompensation of CHF.

Myocardial work – are we ready for a new parameter in clinical practice for evaluating left ventricle function?

Left ventricle systolic function is an essential parameter in different clinical scenarios and the usual methods available for its assessment are sometime suboptimal, depending on the filling conditions of the heart. Therefore, the development and implementation in clinical practice of a new parameter for assessing left ventricle contractile function is desirable. Mechanical work defined as energy transferred to or from an object via the application of force along a displacement seems to be a promising method for myocardial performance estimation. Although initially this parameter was calculated on the left ventricle volume-pressure curve estimated by cardiac catheterization, an easier method considering non-invasive left ventricle pressure and global longitudinal strain assessed by speckle tracking echocardiography was developed recently. Myocardial work offers information regarding the segmental and global function of the left ventricle, and it is considered a more sensitive marker for assessing left ventricle performance compared to ejection fraction and global longitudinal strain. Its applicability in various cardiac pathologies was demonstrated recently in several studies and its use in every day practice may bring important additional information for clinical decision making

Time Series Transcriptomic Analysis by RNA Sequencing Reveals a Key Role of PI3K in Sepsis-Induced Myocardial Injury in Mice.

Septic cardiomyopathy is the main complication and cause of death of severe sepsis with limited therapeutic strategy. However, the molecular mechanism of sepsis-induced cardiac injury remains unclear. The present study was designed to investigate differentially expressed genes (DEGs) involved in the pathogenesis of septic cardiomyopathy induced by cecal ligation and puncture (CLP) in mice. Male C57BL/6J mice (8–10 weeks old) were subjected to CLP with 21-gauge needles for 24, 48, and 72 h. Myocardial function was assessed by echocardiography. The pathological changes of the heart were evaluated by hematoxylin and eosin as well as immunohistochemical staining. Time series RNA sequencing was utilized to investigate the gene expression profiles. CLP surgery resulted in a significant decrease of animal survival rate and left ventricle contractile function, and an increase in cardiac dilation and infiltration of proinflammatory cells including Mac-2+ macrophages in a time-dependent manner. RNA sequencing identified 5,607 DEGs in septic myocardium at 24, 48, and 72 h after CLP operation. Moreover, gene ontology analysis revealed that these DEGs were mainly associated with the biological processes, including cell adhesion, immune system process, inflammatory response, and positive regulation of cell migration. KEGG pathway enrichment analysis indicated that Staphylococcus aureus infection, osteoclast differentiation, leishmaniasis, and ECM-receptor interaction were significantly altered in septic hearts. Notably, Pik3r1 and Pik3r5 were localized in the center of the gene co-expression network, and were markedly upregulated in CLP-induced septic myocardium. Further, blocking PI3Kγ by the specific inhibitor CZC24832 significantly protected against sepsis-induced cardiac impairment. The present study uncovers the gene expression signatures of CLP-induced myocardial injury and sheds light on the role of Pik3r5 in septic cardiomyopathy.

Echocardiographic measurement of left ventricular function following myocardial infarction in adult postnatally overfed mice

Perinatal environment, such as nutritional state, is of major importance for short- and long-term cardio-metabolic status. Postnatal overfeeding (PNOF) induced in rodents by litter size reduction at birth reproduces the effects of childhood overnutrition and was shown to affect the cardiovascular function and to predispose to cardiovascular pathologies. The aim of our work was to follow the evolution of cardiac function for 60 days after in vivo myocardial infarction in control and PNOF mice. C57BL/6 male mice were raised in litter adjusted to 9 or 3 pups for control and PNOF group respectively. After weaning, mice of both groups had free access to standard diet and water. At 4 months, they were either subjected to a permanent ligation of the left anterior descending artery (LAD) to induce myocardial infarction or a sham surgery. Echocardiographic measurements were acquired at baseline and 7, 28, 45 and 60 days after surgery for cardiac function evaluation. Sixty days after surgery, the left ventricle (LV) was harvested for bio-molecular analyzes and lungs were weighed. At basal state, no difference of cardiac function was observed between the 4 groups. In both control and PNOF mice subjected to LAD ligation, the ejection fraction (EF) was significantly decreased 7 days after surgery while the systolic/diastolic LV area was significantly increased, and they both remained stable until 60 days. An increase of cardiac troponin I level and LV mass were also observed 24 h and 60 days after surgery respectively. However, no differences neither in LV contractile function nor in infarct size were noticed between control and PNOF mice. As demonstrated by the decreased LV contractility and dilation, the two groups of mice subjected to myocardial infarction developed heart failure, however, no differences between the control and PNOF groups were observed. Further experiments will be done in order to assess the cardiac expression of genes and proteins involved in heart failure, including the b-myosin heavy chain or the atrial natriuretic peptide.

P197 TAKO TSUBO SYNDROME IN MAN FOR ‘SMART WORKING’ COMPLICATED BY ACUTE HEART FAILURE AND SAM. PRESENCE OF MYOCARDIAL BRIDGE OF IVA ‘INNOCENT BYSTANDER’ OF THE CLINICAL PICTURE

Abstract Male, 59 years old with no significant pathological history or cardiovascular risk factors. Access to the ER ( 12.30 AM ) with infero–lateral STEMI (Killip I, 2 hours of symptom onset; haemodynamic and electrical stability): chest pain associated with profuse sweating and transient arterial hypotension, ST elevation in V3–V6 and inferior leads on the ECG and apical hypokinesia with slight reduction of LVEF (50%) on the Trans–Thoracic Echocardiography. Urgent coronary angiography: non–obstructive coronary arteries stenosis, short intramyocardial tract of DA with moderate systolic compression with ‘milking effect‘. Blood sampling: mild elevation of cardiac troponin hs value (479 pg / ml), mild anemia and thrombocytopenia; normal value of markes of liver and kidney function. Hospitalization in Cardiac ICU with standard antithrombotic and anti–ischemic therapy. 12 hours after admission (01.00 PM) acute low–flow heart failure with pulmonary edema treated with inotropic agent and need of endotracheal intubation and ventilatory support (ineffective attempt of NIV); ECG unchanged from the previous one and appearance of LVEF 25% for akinesia of septum, apex and lateral wall. Peak of troponin 2083 pg / ml III day: effective extubation with successive cycles of NIV and weaning from noradrenaline. Progressive recovery of LVEF with appearance of SAM with LVOT dynamic obstruction (v max&amp;gt; 4m / s at pulsed doppler) and moderate mitral regurgitation: stop inotropic agent and start beta–blocker therapy (atenolol) not tolerated for hypokinetic arrhythmias (also total BAV) and then successful replaced in the following days with low doses of bisoprolol. Post–Iintubation pneumonia treated with antibiotic therapy. X day: hemodynamic and electrical stability, disappearance of the SAM with complete recovery of the left ventricle contractile function, mild mitral regurgitation(minimal valve prolapse) Cardiac MRI: normal LVEF, absence of myocardial LGE with the exception of small areas of the papillary muscles due to traction of the mitral flaps. In the patient‘s medical history: stressful last months related to smart working and family problems; absence of a specific identifiable trigger. Conclusions Stress cardiomyopathy in man patient complicated by progressive acute heart failure and SAM with rapid restitutio ad integrum. Presence of DA myocardial bridge with absence of myocardial LGE on MRI.

Echocardiography in laboratory rabbits

Introduction. Rabbits are used as convenient models for studying drug cardiotoxicity. Echocardiography is one of the most informative non-invasive methods of assessing the cardiovascular system function. In literature, there is no clearly formulated protocol for heart ultrasound examination in rabbits. Purpose was the systematization of literature data on echocardiography techniques in rabbits.Materials and methods. The sources search involved the Scientific Electronic Library eLIBRARY.RU and the National Library of Medicine information base (PubMed.gov). The search covered the 15-year period. Original or review articles containing a detailed description of the echocardiography technique were included.Results and discussion. For animals anesthesia before the study, various drugs combinations based on ketamine, xylazine, medetomidine, zolazepam, tiletamine are used. In rabbits, it is possible to use M-, B-, Doppler echocardiography modes in a wide frequency range (5 – 12 MHz). Parasternal longitudinal, parasternal transverse and apical ultrasound approaches are applied. The parameters of the transmitral blood flow (peak A, peak E, ratio A/E, peak E', the magnitude of regurgitation), as well as the contractile function of the left ventricle (end systolic and diastolic volumes and sizes, stroke volume, cardiac output, shortening fraction) are subject to assessment. The Teicholz and Simpson methods can be used to calculate the ejection fraction. The literature under survey coveres listed parameters of normal values for various ages’ rabbits.Conclusion. Echocardiography is a relatively affordable non-invasive method for studying the state of cardiovascular system in rabbits in an experiment. The method can be used to analyze myocardium size, left ventricle contractile function, and assess the state of heart valvular apparatus. At present, normal values of echocardiographic parameters in rabbits have been experimentally established, which adds to the informative value of the method. Qualitative study performance requires special preparation, including careful animal anesthesia, the choice of the approaches and modes used.

Protective effect of antioxidants on cardiac function in adult offspring exposed to prenatal overnutrition.

Maternal overnutrition-induced fetal programming predisposes offspring to cardiovascular health issues throughout life. Understanding how these adverse cardiovascular effects are regulated at the maternal-fetal crosstalk will provide insight into the mechanisms of these cardiovascular diseases, which will help in further identifying potential targets for intervention. Here, we uncover a role of oxidative stress caused by prenatal overnutrition in governing cardiac damage. Mice exposed to maternal obesity showed remarkable pathological cardiomyocyte hypertrophy (pmale < 0.001, Cohen's dmale = 1.77; pfemale < 0.001, Cohen's dfemale = 1.94), increased collagen content (pmale < 0.001, Cohen's dmale = 2.13; pfemale < 0.001, Cohen's dfemale = 2.71), and increased levels of transforming growth factor β (TGF-β) (pmale < 0.001, Cohen's dmale = 3.02; pfemale < 0.001, Cohen's dfemale = 4.52), as well as left ventricular dysfunction in adulthood. To cope with increased oxidative stress in the myocardial tissue of offspring from obese mothers, we sought to decrease the effect of oxidative stress and prevent the development of these cardiovascular conditions with use of the antioxidant N-acetylcysteine during pregnancy. As predicted, after treatment with the antioxidant, there was greatly mitigated cardiomyocyte hypertrophy (pmale < 0.001, Cohen's dmale = 1.31; pfemale < 0.001, Cohen's dfemale = 0.82) and cardiac fibrosis, including decreased composition of collagen fibers (pmale < 0.01, Cohen's dmale = 1.45; pfemale < 0.05, Cohen's dfemale = 1.23) and reduced levels of TGF-β (pmale < 0.05, Cohen's dmale = 1.83; pfemale < 0.01, Cohen's dfemale = 3.81). We also observed improved left ventricle contractile function together with the alleviation of enhanced oxidative stress in the myocardial tissue of offspring. Collectively, these results established a crucial role of oxidative stress in prenatal overnutrition-associated ventricular remodeling and cardiac dysfunction. Our findings provided an important target for intervention of cardiovascular disease in overnutrition-related fetal programming.

Dyssynchronous cardiomyopathy in patients with WPW syndrome and its reversibility after RFA of accessory pathway

Abstract Introduction In some cases accessory pathway-mediated ventricular preexcitation can be associated with electro-mechanical dyssynchrony and, consequently, with dyssynchrony-related dilated cardiomyopathy, even in the absence of supraventricular tachycardia (SVT). Sometimes rapid progression of ventricular dysfunction developed in such patients after birth. Methods and materials 8 patients with asymptomatic WPW and dyssynchronous cardiomyopathy were examined in our Institute from 2017 till 2019. Four patients of the group were observed in other clinics with dilated cardiomyopathy (DCM) and prescribed appropriate therapy without significant clinical effect. The absence of complaints of heartbeat and episodes of tachycardia at the scheduled Holter monitoring allowed eliminating incessant tachycardia as a possible cause of cardiomyopathy. After radiofrequency ablation (RFA) all patients were performed ECG to assess QRS duration, Holter monitoring, echocardiography (Echo) for assessment of heart chamber volume and left ventricle (LV) contractile function and Speckle tracking – Echo with LV longitudinal strain assessment. The average age of the patients was 9.5 years (from 2 to 14 years). 6 children had heart failure (NYHA Class II). Results According to Echo all patients had widened QRS complex. Dilatation and enlargement of LV volume were marked in 6 pts. According to Echo7 patients had decrease of LV contractile function. According to Speckle tracking – Echo all patients had intraventricular dyssynchrony, decrease of longitudinal strain indices. At intracardiac electrophysiology study right-sided accessory pathways was diagnosed in all patients, successful RFA was performed. Preexitation relapsed, and the repeated RFA was performed in 2 pts. Complications caused by RFA were not marked. After RFA all patients showed a regular normalization of QRS duration. At the 5th day after RFA Echo was performed to all patients. The patients with initially decreased LV ejection fraction had it increased. The patients with initial dilatation and LV volume enlargement had normalization of the given indices. According to Speckle tracking – Echo normalization of global and regional myocardial function, LV longitudinal strain, disappearance of intraventricular and interventricular dyssynchrony were marked in all patients. The index of longitudinal strain was 17,0±0,64% before RFA, after RFA - 23,75±0,92% (p=0,ehab724.035946). Conclusion As a result of RFA of accessory pathways electromechanical resynchronization causes LV demodeling and restoration of its contractile ability. The presented clinical examples are an additional indication for RFA of accessory pathways even in the absence of SVT in patients regardless of age. Funding Acknowledgement Type of funding sources: None.

Evaluation of left ventricular function following myocardial infarction in adult postnatally overfed mice

Perinatal environment, such as nutritional state, is of major importance for short- and long-term cardio-metabolic status. Postnatal overfeeding (PNOF) induced in rodents by litter size reduction at birth reproduces the effects of childhood overnutrition and was shown to affect the cardiovascular function and to predispose to cardiovascular pathologies. The aim of our work was to follow the evolution of cardiac function for 28 days after in vivo myocardial infarction in control or PNOF mice. C57BL/6 male mice were raised in litter adjusted to 9 or 3 pups for control and PNOF group respectively. After weaning, mice of both groups had free access to standard diet and water. At 4 months, they were subjected to permanent ligation of the left anterior descending artery (LAD) to induce myocardial infarction or to sham surgery. Echocardiographic measurements were acquired at baseline and 1, 7, 15 and 28 days after surgery for cardiac function evaluation. Twenty-eight days after surgery, the left ventricle (LV) and lungs were weighed and infarct size was assessed. At basal state, no difference of cardiac function was observed between the 4 groups. In both control and PNOF mice subjected to LAD ligation, the fractional area change (FAC) was significantly decreased 24 h after surgery and the systolic/diastolic LV area was significantly increased 7 d after surgery, and both remained stable until 28 d. However, no differences neither in LV contractile function nor in infarct size were noticed between control and PNOF mice, except for an increased LV mass in PNOF mice. While all groups of mice subjected to myocardial infarction developed heart failure, as demonstrated by decreased LV contractility and dilation, there were no differences between control and PNOF groups. Further measures will be done in order to assess circulating biomarkers as cardiac troponin I (cTnI), brain natriuretic peptide (BNP) and growth differentiation factor-15 (GDF-15).

Thyroid hormone plus dual-specificity phosphatase-5 siRNA increases the number of cardiac muscle cells and improves left ventricular contractile function in chronic doxorubicin-injured hearts.

Rationale: Doxorubicin is a widely used anticancer drug. However, its major side effect, cardiotoxicity, results from cardiomyocyte loss that causes left ventricle (LV) wall thinning, chronic LV dysfunction and heart failure. Cardiomyocyte number expansion by thyroid hormone (T3) during preadolescence is suppressed by the developmental induction of an ERK1/2-specific dual specificity phosphatase 5 (DUSP5). Here, we sought to determine if a brief course of combined DUSP5 suppression plus T3 therapy replaces cardiomyocytes lost due to preexisting doxorubicin injury and reverses heart failure.Methods: We used in vivo-jetPEI to deliver DUSP5 or scrambled siRNA to ~5-week-old C57BL6 mice followed by 5 daily injections of T3 (2 ng/µg body weight). Genetic lineage tracing using Myh6-MerCreMer::Rosa26fs-Confetti mice and direct cardiomyocyte number counting, along with cell cycle inhibition (danusertib), was used to test if this treatment leads to de novo cardiomyocyte generation and improves LV contractile function. Three doses of doxorubicin (20 µg/g) given at 2-weekly intervals, starting at 5-weeks of age in C57BL6 mice, caused severe heart failure, as evident by a decrease in LV ejection fraction. Mice with an ~40 percentage point decrease in LVEF post-doxorubicin injury were randomized to receive either DUSP5 siRNA plus T3, or scrambled siRNA plus vehicle for T3. Age-matched mice without doxorubicin injury served as controls.Results: In uninjured adult mice, transient therapy with DUSP5 siRNA and T3 increases cardiomyocyte numbers, which is required for the associated increase in LV contractile function, since both are blocked by danusertib. In mice with chronic doxorubicin injury, DUSP5 siRNA plus T3 therapy rebuilds LV muscle by increasing cardiomyocyte numbers, which reverses LV dysfunction and prevents progressive chamber dilatation.Conclusion: RNA therapies are showing great potential. Importantly, a GMP compliant in vivo-jetPEI system for delivery of siRNA is already in use in humans, as is T3. Given these considerations, our findings provide a potentially highly translatable strategy for addressing doxorubicin cardiomyopathy, a currently untreatable condition.

Valsartan improves left ventricle contractility and prevents its remodeling in patients with dual chamber pacemaker

Abstract Introduction Permanent right ventricle pacing leads to left ventricle dyssynchrony, systolic dysfunction, remodeling, and symptomatic heart failure in the long run. Valsartan is well known for its preventive anti-remodeling function in the post infarction heart remodeling. Objectives To assess the effect of valsartan on left ventricle contractility, measured as global longitudinal stain, and its remodeling in patients with second and third degree atrioventricular block with first-time implantation of dual chamber pacemaker. Methods This was a randomized, double-blind, placebo controlled single center study. One hundred eligible patients were assigned in a 1:1:1 fashion to receive placebo, valsartan 80mg or 160mg once daily, respectively. Echocardiographic assessment of left ventricle geometry, its systolic and diastolic function was performed at baseline and at twelve months. Global longitudinal strain (GLS) was measured off-line with EchoPac software. One patient from placebo group suffered stroke. We present the baseline date for 100 enrolled patients and follow-up data for 88 patients who have completed the study. Data in valsartan arms are pooled in one group. Results Results are presented in table. Data are presented as mean and standard deviation. Valsartan alleviates diastolic dysfunction, left ventricle dilation and protects from loss of systolic function. Conclusion Valsartan has protective effect of left ventricle contractile function and remodeling. It may be useful in prevention of pacing induced heart failure. (ClinicalTrials Identifier NCT01805804) Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Medical University of Silesia

The valve-preserving operations on a chordo-papillary continuum in a mitral valve prosthesis

Objective. Studying of morphometric indices and contractility of left ventricle in various variants of preservation of chordo-papillary continuum in late period after the mitral valve prosthesis.&#x0D; Materials and methods. Analysis in 634 patients with isolated mitral valve failure, who were surgically treated from Sept. 1 2005 till Jan. 1 2007, was conducted. While the mitral valve prosthesis the chordo-papillary continuum was conducted, using preservation of the mitral valve posterior flap (41 patients) and simultaneous translocations of chordo-papillary muscles of anterior flap and preservation of posterior flap of a mitral valve (57 patients).&#x0D; Results. While comparing morphometric indices of left ventricle in left ventriculomegaly on a hospital stage and in late postoperative period when complete excision of a mitral valve in its prosthesis was performed, and when posterior flap was preserved, and simultaneously the posterior and anterior mitral valve flaps the improvement of the indices was observed, as well as normalization of a contractile function of left ventricle if a subvalvular space is preserved.&#x0D; Conclusion. Preservation of chordo-papillary continuum while performing the mitral valve prosthesis improves morphometric indices and contractility of left ventricle on a hospital stage and in late follow-up period.

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.

Increased serum uric acid levels in patients with non-valvular atrial fibrillation

Serum uric acid (SUA) is a simple and independent marker of morbidity and mortality in a variety of cardiovascular diseases. In this study we aimed to examine the relationship between serum uric acid levels and clinical, biological and echocardiographic characterstics in patients with non-valvular atrial fibrillation (AF). One hundred and seventy patients with non-valvular atrial fibrillation were included (mean age: 66.3 ± 8.5 years; 37% male patients). Hyperuricemia was defined as SUA ≥ 360 μmol/L in women and ≥ 446 μmol/L in men determined determined according to receiver operating characteristic curve. Clinical, biological and echocardiographic characterestics were compared in patients with ( n = 51) and without hyperuricemia ( n = 119). In AF patients, those with hyperuricemia had the most adverse biological risk profile including the highest rates of renal dysfunction ( P < 0.001) and the highest mean level of fibrinogen ( P = 0.033), c-reactive protein ( P = 0.05), calcemia ( P = 0.016) and leucocytosis ( P = 0.03). Patients with hyperuricemia showed also more enlarged left atrium ( P = 0.039) and lower left ventricle ejection fraction ( P = 0.01) and peak myocardial systolic velocity measured at the mitral annulus (Sa) in tissue Doppler imaging (TDI) ( P = 0.01) High serum uric acid levels were associated with a low left ventricle contractile function, enlargement of left atrium, inflammatory biological profile and could provide additional prognostic information on future thromboembolic events in patients with AF.