Left Ventricular Contractility Research Articles

Global left ventricular strains and left atrial volumes are not associated in healthy adults – Detailed analysis from the three-dimensional speckle-tracking echocardiographic MAGYAR-Healthy Study

IntroductionDuring the heart cycle, left ventricular (LV) contractility is characterized by complex deformation and rotational mechanics, resulting in LV ejection. The present study seeks to expand our knowledge by examining dependence of LV strains representing LV deformation on left atrial (LA) volumes in healthy circumstances. Therefore, the aim of this study was to evaluate the associations between LA volumes and LV strains as assessed simultaneously by three-dimensional speckle-tracking echocardiography (3DSTE) in normal healthy adults. MethodsThe present study consisted of 302 healthy adults, but according to exclusion criteria, 137 subjects were excluded due to inferior image quality. The final population comprised 165 individuals (mean age: 33.1 ± 12.3 years, 75 males) who were voluntarily recruited for screening. Two-dimensional echocardiography extended with 3DSTE was performed in all subjects for detailed LV/LA analysis. ResultsOverall feasibility for simultaneous assessment of LV strains and LA volumes proved to be 55 % with excellent intra- and interobserver correlations. All global LV strains were similar, regardless of the LA volumes examined. All LA volumes and volume-based functional properties respecting the cardiac cycle were similar, regardless the global LV strains examined. ConclusionsLV strains and LA volumes can be simultaneously assessed by 3DSTE. Global LV strains and LA volumes are not associated in healthy adults.

Catecholamine treatment induces reversible heart injury and cardiomyocyte gene expression

BackgroundCatecholamines are commonly used as therapeutic drugs in intensive care medicine to maintain sufficient organ perfusion during shock. However, excessive or sustained adrenergic activation drives detrimental cardiac remodeling and may lead to heart failure. Whether catecholamine treatment in absence of heart failure causes persistent cardiac injury, is uncertain. In this experimental study, we assessed the course of cardiac remodeling and recovery during and after prolonged catecholamine treatment and investigated the molecular mechanisms involved.ResultsC57BL/6N wild-type mice were assigned to 14 days catecholamine treatment with isoprenaline and phenylephrine (IsoPE), treatment with IsoPE and subsequent recovery, or healthy control groups. IsoPE improved left ventricular contractility but caused substantial cardiac fibrosis and hypertrophy. However, after discontinuation of catecholamine treatment, these alterations were largely reversible. To uncover the molecular mechanisms involved, we performed RNA sequencing from isolated cardiomyocyte nuclei. IsoPE treatment resulted in a transient upregulation of genes related to extracellular matrix formation and transforming growth factor signaling. While components of adrenergic receptor signaling were downregulated during catecholamine treatment, we observed an upregulation of endothelin-1 and its receptors in cardiomyocytes, indicating crosstalk between both signaling pathways. To follow this finding, we treated mice with endothelin-1. Compared to IsoPE, treatment with endothelin-1 induced minor but longer lasting changes in cardiomyocyte gene expression. DNA methylation-guided analysis of enhancer regions identified immediate early transcription factors such as AP-1 family members Jun and Fos as key drivers of pathological gene expression following catecholamine treatment.ConclusionsThe results from this study show that prolonged catecholamine exposure induces adverse cardiac remodeling and gene expression before the onset of left ventricular dysfunction which has implications for clinical practice. The observed changes depend on the type of stimulus and are largely reversible after discontinuation of catecholamine treatment. Crosstalk with endothelin signaling and the downstream transcription factors identified in this study provide new opportunities for more targeted therapeutic approaches that may help to separate desired from undesired effects of catecholamine treatment.

The additive prognostic value of end-systolic pressure-volume relation by stress CMR in patients with known or suspected coronary artery disease.

The difference between rest and peak stress end-systolic pressure-volume relation (ΔESPVR) is an afterload-independent index of left ventricular (LV) contractility. We assessed the independent prognostic value of ΔESPVR index by dipyridamole stress-cardiovascular magnetic resonance (CMR) in patients with known/suspected coronary artery disease (CAD). We considered 196 consecutive patients (62.74 ± 10.66years, 49 females). Wall motion and perfusion abnormalities at rest and peak stress were analysed. Replacement myocardial fibrosis was detected by late gadolinium enhancement(LGE) technique. The ESPVR was evaluated at rest and peak stress from raw measurement of systolic arterial pressure and end-systolic volume by biplane Simpson's method. A reduced ΔESPVR index (≤ 0.02mmHg/mL/m2) was found in 88(44.9%) patients and it was associated with a lower LV ejection fraction(EF) and with a higher frequency of abnormal stress CMR and myocardial fibrosis. During a mean follow-up of 53.17 ± 28.21months, 50(25.5%) cardiac events were recorded: 5 cardiac deaths, 17 revascularizations, one myocardial infarction, 23 hospitalisations for heart failure or unstable angina, and 4 ventricular arrhythmias. According to Cox regression analysis, diabetes, family history, LVEF, abnormal stress CMR, myocardial fibrosis, and reduced ΔESPVR were significant univariate prognosticators. In the multivariate analysis the independent predictors were ΔESPVR index ≤ 0.02mmHg/mL/m2 (hazard ratio-HR = 2.58, P = 0.007), myocardial fibrosis (HR = 2.13, P = 0.036), and diabetes (HR = 2.33, P = 0.012). ΔESPVR index by stress-CMR was independently associated with cardiac outcomes in patients with known/suspected CAD, in addition to replacement myocardial fibrosis and diabetes. Thus, the assessment of ΔESPVR index may be included into the standard stress-CMR exam to further stratify the patients.

Comprehensive Assessment of Cardiac Function in Breast Cancer Patients: Integrating Multiparametric Speckle Tracking Imaging and Conventional Echocardiography Parameters.

Purpose The purpose of this study is to comprehensively evaluate the role of different echocardiography parameters in breast cancer patients undergoing chemotherapy. While echocardiography examination with calculation of ejection fraction (EF), is pivotal for patient monitoring, its operator dependence and insensitivity to subtle changes in left ventricular (LV) contractility present challenges. Global longitudinal strain (GLS), derived from speckle tracking, is more sensitive and stable than EF. Our research aimed to delineate supplementary echocardiography measurements beneficial for the cardiological monitoring of breast cancer patients. Methods Patients were followed up with echocardiography at baseline, during, and after the chemotherapy. Conventional echocardiography and multiple speckle tracking imaging parameters including myocardial work index, atrial strain, twist, and automatic EF were investigated. Results A total of 25 patients were recruited. A subset (15/25) exhibited pronounced GLS reduction, associated with decreased EF and altered cardiac mechanics. Patients with unchanged GLS were often hypertensive and on specific medications, in particular angiotensin-converting enzyme inhibitors (ACE inhibitors)/angiotensin II receptor blockers (ARBs), potentially indicating protective effects. Despite stability in other parameters, GLS and EF sensitivity highlight their importance. A strong correlation between manual and automated EF measurement methods was also observed. Conclusion Despite the small sample size, across diverse echocardiography parameters, GLS and EF are primarily affected by chemotherapy. Hypertensive individuals exhibited lower susceptibility to chemotherapy-induced damage, likely attributed to the cardioprotective properties of ACE inhibitors and angiotensin II receptor blockers. A strong correlation between automatic and Simpson-based EF was found.

Novel portable hypothermic machine perfusion preservation device enhances cardiac viability of donated human hearts.

Heart transplant remains the gold standard treatment for patients with advanced heart failure. However, the list of patients waiting for a heart transplant continues to increase. We have developed a portable hypothermic oxygenated machine perfusion device, the VP.S ENCORE®, to extend the allowable preservation time. The purpose of this study was to test the efficacy of the VP.S. ENCORE® using deceased donors derived hearts. Hearts from brain-dead donors not utilized for transplant (n = 11) were offered for research from the Texas Organ Sharing Alliance (TOSA), South and Central Texas' Organ Procurement Organization (OPO) and were preserved in the VP.S ENCORE® for 4 (n = 2), 6 (n = 3), and 8 (n = 3) hours or were kept in static cold storage (SCS) (n = 3). After preservation, the hearts were placed in an isolated heart Langendorff model for reperfusion and evaluated for cardiac function. The mean donor age was 37.82 ± 12.67 with the youngest donor being 19 and the oldest donor being 58 years old. SCS hearts mean weight gain (%) was -1.4 ± 2.77, while perfused at 4 h was 5.6 ± 6.04, perfused at 6 h 2.1 ± 6.04, and 8 h was 7.2 ± 10.76. Venous and arterial lactate concentrations were less than 2.0 mmol/L across all perfused hearts. Left ventricular contractility (+dPdT, mmHg/s) for 4 h (1,214 ± 1,064), 6 (1,565 ± 141.3), and 8 h (1,331 ± 403.6) were within the range of healthy human heart function. Thus, not significant as compared to the SCS group (1,597 ± 342.2). However, the left ventricular relaxation (mmHg/s) was significant in 6-hour perfused heart (p < 0.05) as compared to SCS. Gene expression analysis of inflammation markers (IL-6, IL-1β) showed no significant differences between SCS and perfused hearts, but a 6-hour perfusion led to a downregulated expression of these markers. The results demonstrate that the VP.S ENCORE® device enhances cardiac viability and exhibits comparable cardiac function to a healthy heart. The implications of these findings suggest that the VP.S ENCORE® could introduce a new paradigm in the field of organ preservation, especially for marginal hearts.

Limitations of Diagnosis of Ischemic Left Ventricular Dysfunction Using the Values of Strain, Twist and Untwist in Patients With Myocardial Infarction of Various Localization.

To compare capabilities for diagnosing regional and global myocardial dysfunction using the values of longitudinal and circular strain, left ventricular (LV) torsion and untwisting in patients with myocardial infarction (MI) of various locations. Patients included in the study (n=121) were divided into three groups: patients with unstable angina (n=30), patients with anterior MI (n=45), and patients with inferior MI (n=46). Clinical, laboratory and instrumental test were performed, including echocardiography. For a quantitative analysis of LV contractility, the maximum systolic peaks of regional and global longitudinal and circular strain, systolic and diastolic rotation, LV torsion and untwisting were measured. Anterior MI was characterized by injury of the LV apical segments, while inferior MI was characterized by injury of the basal segments. In anterior MI, the longitudinal strain was reduced less than 14.5% and circular strain less than 19.3% in the apical segment of the LV anteroseptal wall (ASW). In akinesia of the LV ASW apical segment, longitudinal and circular strains were reduced less than 10%. The magnitude of the circular strain of the LV ASW apical segment (diagnostic threshold 19.3%, sensitivity (Se) 87%, specificity (Sp) 90%) was superior to that of the longitudinal strain as a diagnostic marker for regional ischemic dysfunction in anterior MI. The magnitude of the circular strain of the basal segment of the LV inferior wall in inferior MI has a greater diagnostic value for identifying regional systolic dysfunction than the value of the longitudinal strain of this LV segment. The diagnostic threshold was 17.3%, Se 79%, Sp 80%. A decrease in the circular strain of the LV ASW less than 19.3% in the LV apical segment is more specific (Sp 90%) for diagnosing regional systolic dysfunction in anterior MI than a decrease in longitudinal strain. A circular strain value of less than 17.3% in the basal segment of the LV inferior wall is more specific (Sp 80%) than the longitudinal strain of this segment for diagnosing regional systolic dysfunction in inferior MI. Predominant injury to the LV apex in anterior MI can cause systolic and diastolic myocardial dysfunction, which is manifested by a decrease in LV circular deformation, torsion and untwisting.

Urgent Cardiosurgical Treatment of a Military Servant with a Moving Thrombus in the Area of the Left Ventricular Apical Aneurysm (Case Report)

Against the background of military operations, post-traumatic stress disorder, the progression of the atherosclerotic process is observed, which can lead to myocardial infarction even in young people. Left ventricular aneurysm (LVA) in military personnel is the result of untimely revascularization of an infarct-related artery, gunshot wound to the heart, chest trauma, etc. The presence of a dyskinetic area promotes formation of blood clots in the LVA cavity. LVA thrombosis is associated with an increased risk of embolism, ischemic stroke, and death.&#x0D; Case description. A 37-year-old military servant A. was urgently hospitalized to the National Amosov Institute of Cardiovascular Surgery of the National Academy of Medical Sciences of Ukraine with a mobile thrombus in the area of LVA, size 4.5 x 3 cm, with signs of lysis and a threat of separation according to echo data. The patient was found to suffer Q-wave myocardial infarction 5 months ago; at the time of examination there was decompensation of the condition and a decrease in the left ventricular contractility to 34%. The patient underwent urgent operation: on-pump coronary artery bypass grafting, LVA resection with thrombectomy. The duration of the operation was 7 hours, the aortic cross-clamp time was 53 minutes, the perfusion time was 93 minutes, the blood loss was 500 ml. The postoperative period was uneventful. The patient was discharged on the 7th day with improvement, the ejection fraction was 40%.&#x0D; Conclusion. The lack of an opportunity to conduct timely electrocardiography and echo for military personnel with acute chest pain reduces the chances of diagnosis and treatment of myocardial infarction within the therapeutic window, which leads to the occurrence of complicated forms of coronary heart disease, namely LVA. Echo is of crucial importance in deciding on emergency cardiac surgery for thrombosed LVA.

The estimation of left ventricular myocardial work indicators during cardiac ultrasound imaging: methodology, capabilities, advantages and limitations

This article is dedicated to the assessment of left ventricular (LV) myocardial work indicators using the method of constructing pressure-strain loops, a new tool in echocardiography that can take into account the influence of cardiac afterload on LV contractility. The algorithm of actions for estimating myocardial work, possible difficulties and features of calculating its main indicators are described in detail, the limitations and disadvantages of the method are discussed. The normal ranges of LV myocardial work indicators are given in the article, and it presents their typical changes and the advantages of using in various diseases and pathological conditions of the heart.

Lactate infusion elevates cardiac output through increased heart rate and decreased vascular resistance: a randomised, blinded, crossover trial in a healthy porcine model

BackgroundLactate is traditionally recognized as a by-product of anaerobic metabolism. However, lactate is a preferred oxidative substrate for stressed myocardium. Exogenous lactate infusion increases cardiac output (CO). The exact mechanism underlying this mechanism has yet to be elucidated. The aim of this study was to investigate the cardiovascular mechanisms underlying the acute haemodynamic effects of exogenous lactate infusion in an experimental model of human-sized pigs.MethodsIn this randomised, blinded crossover study in eight 60-kg-pigs, the pigs received infusions with one molar sodium lactate and a control infusion of tonicity matched hypertonic saline in random order. We measured CO and pulmonary pressures using a pulmonary artery catheter. A pressure–volume admittance catheter in the left ventricle was used to measure contractility, afterload, preload and work-related parameters.ResultsLactate infusion increased circulating lactate levels by 9.9 mmol/L (95% confidence interval (CI) 9.1 to 11.0) and CO by 2.0 L/min (95% CI 1.2 to 2.7). Afterload decreased as arterial elastance fell by -1.0 mmHg/ml (95% CI -2.0 to -0.1) and systemic vascular resistance decreased by -548 dynes/s/cm5 (95% CI -261 to -835). Mixed venous saturation increased by 11 percentage points (95% CI 6 to 16), whereas ejection fraction increased by 16.0 percentage points (95% CI 1.1 to 32.0) and heart rate by 21 bpm (95% CI 8 to 33). No significant changes in contractility nor preload were observed.ConclusionLactate infusion increased cardiac output by increasing heart rate and lowering afterload. No differences were observed in left ventricular contractility or preload. Lactate holds potential as a treatment in situations with lowered CO and should be investigated in future clinical studies.Graphical

Evaluation of the translation of multiple cardiovascular regulatory mechanisms in the anesthetized dog

The strategic and targeted use of an anesthetized canine cardiovascular model early in drug discovery enables a comprehensive cardiovascular and electrophysiological assessment of potential safety liabilities and guides compound selection prior to initiation of chronic toxicological studies. An ideal model would enable exposure-response relationships to guide safety margin calculations, have a low threshold to initiate, and have quick delivery of decision quality data. We have aimed to profile compounds with diverse mechanism of actions (MoAs) of “non-QT” cardiovascular drug effects and evaluate the ability of nonclinical in vivo cardiovascular models to detect clinically reported effects. The hemodynamic effects of 11 drugs (atropine, itraconazole, atenolol, ivabradine, milrinone, enalaprilat, fasudil, amlodipine, prazosin, amiloride, and hydrochlorothiazide) were profiled in an anesthetized dog cardiovascular model. Derived parameters included: heart rate, an index of left ventricular contractility, mean arterial pressure, systemic vascular resistance, and cardiac output. Species specific plasma protein data was generated (human, dog) and utilized to calculate free drug concentrations. Using the anesthetized dog cardiovascular model, 10 of the 11 drugs displayed the predicted changes in CV parameters based on their primary MoAs and corresponding clinically described effects. Interestingly but not unexpected, 1 of 11 failed to display their predicted CV pattern which is likely due to a delay in pharmacodynamic effect that is beyond the duration of the experimental model (hydrochlorothiazide). The analysis from the current study supports the strategic use of the anesthetized dog model early in the drug discovery process for a comprehensive cardiovascular evaluation with good translation to human.

Physical exercise is essential for increasing ventricular contractility in hypertensive rats treated with losartan.

The treatment of hypertensive patients with losartan is very common. Despite the reduction in blood pressure, its effects on cardiac contractility and sympathetic autonomic drive are still controversial. In turn, aerobic physical training (APT) also presents an important therapeutic option, providing significant improvements in cardiovascular autonomic control, however little is known about its effects on cardiac contractility, especially when associated with losartan. Therefore, we investigated in spontaneously hypertensive rats (SHR) the effects of losartan and APT on cardiac hemodynamics and functionality, with emphasis on autonomic tonic balance and cardiac contractility. Sixty-four SHR (18 weeks old) were divided into four groups (N = 16): vehicle; vehicle submitted to APT through swimming for 12 weeks; treated with losartan (5 mg·kg-1·d-1) for 12 weeks; and treated with losartan associated with APT. The groups were submitted to cardiac morphological and functional analysis by echocardiography; double blockade of cardiac autonomic receptors with atropine and propranolol; and coronary bed reactivity and left ventricular contractility analyses by the Langendorff technique. APT improved functional parameters and autonomic balance by reducing sympathetic drive and/or increasing vagal drive. In contrast, it promoted a concentric remodeling of the left ventricle (LV). Treatment with losartan reduced sympathetic autonomic drive and cardiac morphological parameters, but there were no significant gains in cardiac functionality and contractility. When combined, the concentric remodeling of the LV to APT was abolished and gains in cardiac functionality and contractility were observed. Our findings suggest that the effects of losartan and APT are complementary and should be applied together in the treatment of hypertension. In spontaneously hypertensive rats, the combination of aerobic physical training with losartan treatment was crucial to greater blood pressure reductions and an increase in left ventricular contractility. Furthermore, losartan treatment prevented the concentric left ventricular remodeling caused by aerobic physical training.

Left ventricular mechanical dyssynchrony after chemotherapy in breast cancer patients with normal rest gated SPECT-MPI.

Early diagnosis of chemotherapy-induced cardiotoxicity plays an important role in preventing heart failure. The main aim of our study was to assess left ventricular (LV) dyssynchrony measured by phase analysis of gated single-photon emission computed tomography (SPECT) as an early sign of cardiotoxicity after breast cancer chemotherapy. This cross-sectional study was conducted on patients with stage ≤ 3 breast cancer and no history of cardiovascular disease or diabetes. After mastectomy, the patients underwent rest gated SPECT myocardial perfusion imaging (MPI). Sixty patients with normal gated SPECT-MPI were selected and the imaging was performed after chemotherapy with doxorubicin, cyclophosphamide and paclitaxel. LV function and contractility parameters were extracted by QGS software and the results were compared with the t test method. The abnormality of at least one of the three phase analysis indices was considered as left ventricular dyssynchrony (LVD). The average LV end-systolic volume and ejection fraction (LVEF) before and after chemotherapy were (16.2 ± 8.0ml and 21.6 ± 11.6ml) and (73.4 ± 7.9% and 67.5 ± 9.2%) respectively, which showed a significant decrease (P < 0.05). In 2 patients (3.3%), the LVEF decreased to less than 50% after chemotherapy. The average parameters of left ventricular contractility before and after chemotherapy were, respectively, as follows: PHB (24.1 ± 7.5 and 33.8 ± 16.4), PSD (9.4 ± 6.1 and 5.7 ± 1.9) and entropy (28.9 ± 7.1 and 35.6 ± 9.7), which showed a significant increase (P < 0.05). LVD was observed in 14 patients (23.4%) after chemotherapy and prevalence of LVD was significantly higher in patients who had received a cumulative dose of doxorubicin of more than 400mg/m2 (P = 0.005). There was no relationship between age and body mass index with the incidence of LVD after chemotherapy (P > 0.05). Using phase analysis of gated SPECT-MPI, chemotherapy-induced LVD was seen in a significant number of patients with breast cancer, especially with a high cumulative dose of doxorubicin. LVD might indicate chemotherapy-induced cardiotoxicity before LVEF becomes abnormal.

Transcriptomic Changes in the Myocardium and Coronary Artery of Donation after Circulatory Death Hearts following Ex Vivo Machine Perfusion.

Donation after circulatory death (DCD) hearts are predominantly maintained by normothermic blood perfusion (NBP). Nevertheless, it was shown that hypothermic crystalloid perfusion (HCP) is superior to blood perfusion to recondition left ventricular (LV) contractility. However, transcriptomic changes in the myocardium and coronary artery in DCD hearts after HCP and NBP have not been investigated yet. In a pig model, DCD hearts were harvested and maintained for 4 h by NBP (DCD-BP group, N = 8) or HCP with oxygenated histidine-tryptophane-ketoglutarate (HTK) solution (DCD-HTK, N = 8) followed by reperfusion with fresh blood for 2 h. In the DCD group (N = 8), hearts underwent reperfusion immediately after procurement. In the control group (N = 7), no circulatory death was induced. We performed transcriptomics from LV myocardial and left anterior descending (LAD) samples using microarrays (25,470 genes). We applied the Boruta algorithm for variable selection to identify relevant genes. In the DCD-BP group, compared to DCD, six genes were regulated in the myocardium and 1915 genes were regulated in the LAD. In the DCD-HTK group, 259 genes were downregulated in the myocardium and 27 in the LAD; and 52 genes were upregulated in the myocardium and 765 in the LAD, compared to the DCD group. We identified seven genes of relevance for group identification: ITPRIP, G3BP1, ARRDC3, XPO6, NOP2, SPTSSA, and IL-6. NBP resulted in the upregulation of genes involved in mitochondrial calcium accumulation and ROS production, the reduction in microvascular endothelial sprouting, and inflammation. HCP resulted in the downregulation of genes involved in NF-κB-, STAT3-, and SASP-activation and inflammation.

Cardiac effects of myoregulin in ischemia-reperfusion

Myoregulin is a recently discovered micropeptide that controls calcium levels by inhibiting the intracellular calcium pump sarco-endoplasmic reticulum Ca2+-ATPase (SERCA). Keeping calcium levels balanced in the heart is essential for normal heart functioning, thus myoregulin has the potential to be a crucial regulator of cardiac muscle performance by reducing the rate of intracellular Ca2+ uptake. We provide the first report of myoregulin mRNA expression in human heart tissue, absence of expression in human plasma, and the effects of myoregulin on cardiac hemodynamics in an ex vivo Langendorff isolated rat heart model of ischemia/reperfusion. In this preliminary study, myoregulin provided a cardio-protective effect, as assessed by preservation of left ventricular contractility and relaxation, during ischemia/reperfusion. This study provides the foundation for future research in this area.

Diagnostic value of non-invasive indicators of myocardial function in patients after myocardial infarction

Aim. To study the diagnostic value of myocardial function parameters to assess their predictive ability in relation to left ventricular (LV) global contractility in patients after myocardial infarction (MI).Material and methods. The final analysis included 97 patients with MI aged 55,9±8,6 years. We performed standard two-dimensional echocardiography and speckle tracking echocardiography with analysis of following myocardial function parameters: global work index (GlobalWI, mm Hg %); global constructive work (GlobalCW, mm Hg %); global wasted work (GlobalWW, mm Hg %); global work efficiency (GlobalWE). The probability of ejection fraction (EF) reduction was analyzed using ROC curves using three criteria. The function parameters with the maximum sum of sensitivity and specificity were selected as the cut-off point.Results. On days 7-9 after MI, depending on the EF, patients were divided into 3 groups: "REF" — patients with EF &lt;40%); "MREF" — with EF from 40 to 49%, and "PEF" — patients with EF ³50%. By the 24th week, GlobalWI increased by 23% in the PEF group and by 33% in the MREF group. In the REF group, there was a gradual decrease in GlobalWI until the end of the study. In the PEF group, GlobalCW increased by 21% by week 24. By the end of follow-up, an increase in GlobalWW of 15% was observed in the REF group. GlobalWI, GlobalCW and GlobalWW were found to have the highest sensitivity values (60%) for reduced EF, ranging from 4049% at 24 weeks from the index event. GlobalWW had the highest specificity value (80%). With regard to a decrease in EF &lt;40% by week 24, the GlobalWW had the highest sensitivity (50%) and specificity (70%).Conclusion. Parameters of myocardial function have diagnostic and prognostic value for assessing LV systolic function after MI. Already in the acute period, myocardial function parameters can be used to determine the risk of decreased LV global contractility.

Preclinical cardiovascular safety assessment of pharmacology-toxicology relationship for a set of novel kinase inhibitors.

Cardiovascular toxicity is one of the more common causes of attrition in preclinical and clinical drug development. Preclinical cardiovascular safety assessment involves numerous in vitro and in vivo endpoints which are being continually reviewed and improved to lower the incidence of cardiovascular toxicity that manifests only after the initiation of clinical trials. An example of notable preclinical toxicity is necrosis in the papillary muscle of the left ventricle in dogs that is induced by exaggerated pharmacological effects of vasodilators or positive inotropic/vasodilating off-target drug effects. Two distinct, small-molecule inhibitors that target an intracellular kinase, Compound A and Compound B, were profiled in 2-week dose-range finding and 4-week toxicity studies. Serum cardiac troponin (cTnI) was evaluated after a single dose and after 2-week and 4-week repeat dose studies with each kinase inhibitor. Acute effects on hemodynamic (heart rate, blood pressures, left ventricular contractility) and electrocardiographic (QTcV, PR, QRS intervals) endpoints by each inhibitor were assessed in an anesthetized dog cardiovascular model. Cardiovascular degeneration/necrosis with and without fibrosis was observed in dogs and correlated to increases in serum cTnI in repeat-dose toxicity studies. At the same doses used in toxicologic assessments, both kinase inhibitors produced sustained increases in heart rate, left ventricular contractility, and cardiac output, and decreases in mean arterial pressure. Cardiac pathology findings associated with these 2 kinase inhibitors were accompanied not only by cardiac troponin elevations but also associated with hemodynamic changes, highlighting the importance of the link of the physiologic-toxicologic interplay in cardiovascular safety assessment.

Exploring the Connection Between Relaxed Myosin States and the Anrep Effect.

The Anrep effect is an adaptive response that increases left ventricular contractility following an acute rise in afterload. Although the mechanistic origin remains undefined, recent findings suggest a two-phase activation of resting myosin for contraction, involving strain-sensitive and posttranslational phases. We propose that this mobilization represents a transition among the relaxed states of myosin-specifically, from the super-relaxed (SRX) to the disordered-relaxed (DRX)-with DRX myosin ready to participate in force generation. This hypothesis offers a unified explanation that connects myosin's SRX-DRX equilibrium and the Anrep effect as parts of a singular phenomenon. We underscore the significance of this equilibrium in modulating contractility, primarily studied in the context of hypertrophic cardiomyopathy, the most common inherited cardiomyopathy associated with diastolic dysfunction, hypercontractility, and left ventricular hypertrophy. As we posit that the cellular basis of the Anrep effect relies on a two-phased transition of myosin from the SRX to the contraction-ready DRX configuration, any dysregulation in this equilibrium may result in the pathological manifestation of the Anrep phenomenon. For instance, in hypertrophic cardiomyopathy, hypercontractility is linked to a considerable shift of myosin to the DRX state, implying a persistent activation of the Anrep effect. These valuable insights call for additional research to uncover a clinical Anrep fingerprint in pathological states. Here, we demonstrate through noninvasive echocardiographic pressure-volume measurements that this fingerprint is evident in 12 patients with hypertrophic obstructive cardiomyopathy before septal myocardial ablation. This unique signature is characterized by enhanced contractility, indicated by a leftward shift and steepening of the end-systolic pressure-volume relationship, and a prolonged systolic ejection time adjusted for heart rate, which reverses post-procedure. The clinical application of this concept has potential implications beyond hypertrophic cardiomyopathy, extending to other genetic cardiomyopathies and even noncongenital heart diseases with complex etiologies across a broad spectrum of left ventricular ejection fractions.

Acute Myocardial Infarction or Broken Heart with Takotsubo Cardiomyopathy? Realm of Mystification after Suicidal Hanging

Abstract Takotsubo cardiomyopathy is a rare immune-endocrinologic cause of acute and rapidly reversible left ventricular dysfunction, usually resembling acute myocardial infarction (AMI) and triggered by emotional or physical stress. We described a case of such syndrome in a 27-year-old female after an attempted suicidal hanging, whose initial clinical symptoms and electrocardiography (ECG) findings were misleading to AMI. On admission, the patient was unconscious and hypoxic. Echocardiography demonstrated a severe left ventricular systolic dysfunction with akinesis in the mid and anterior septum and apex (a typical ballooning pattern), which raised suspicion of takotsubo cardiomyopathy. Our patient developed chest pain, a day after the suicidal attempt. Emergent coronary angiography revealed no evidence of occlusion, confirmed diagnosis of takotsubo cardiomyopathy was made. The patient was managed with medical therapy. On a week later follow-up, the patient was totally asymptomatic with a reversal of ECG changes, and the left ventricular contractility was improved within 30 days.

Prediction of myocardial contractility after coronary bypass surgery according to preoperative contrast-enhanced magnetic resonance imaging and echocardiography

To establish the criteria for reversibility of myocardial contractility in patients with coronary artery disease (CAD) after coronary artery bypass grafting considering data of cardiac magnetic resonance imaging (MRI) and echocardiography. We studied the results of coronary artery bypass grafting in 186 patients with CAD complicated by reduced left ventricular ejection fraction (<30%). All patients underwent cardiac MRI and echocardiography before surgery. Immediate and long-term results were evaluated according to echocardiography and MRI data. We confirmed the previously established predictors of improvement in left ventricular contractility: diastolic IVST ≥10.5 mm and PWT ≥9.5 mm, score of LV myocardium damage according to MRI with delayed contrast enhancement (p<0.05). Multivariate analysis makes it possible to calculate prognostic index and obtain information about further myocardial contractility after revascularization with an error of 6%. Echocardiography and contrast-enhanced cardiac MRI are valuable to assess morphological and functional state of the left ventricle in patients with ischemic cardiomyopathy and preoperatively determine functional reserve of the myocardium.

Usefulness of tissue Doppler-derived left ventricular isovolumic contraction velocity in patients with heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is a group of diseases classified by left ventricular (LV) EF, a measure of pump function. However, LVEF does not reflect LV contractility. Previous studies have shown that tissue Doppler-derived LV isovolumic contraction velocity (IVCv) correlates well with the LV peak dP/dt, an index of LV contractility. We explored whether LV IVCv is associated with 1-year post-discharge outcomes in HFpEF. We enrolled 113 patients (median age, 86 years, 45 male) with HFpEF (EF on admission ≥ 50%) who were admitted to our hospital for the treatment of acute HF. Clinical characteristics including echocardiographic data were obtained before discharge. IVCv was obtained from the tissue Doppler waveforms of both the septal and lateral mitral annulus of the apical 4-chamber view and averaged data were used. Primary outcomes were all-cause death or unplanned hospitalization due to HF within the first year. Among all patients, median LVEF was 61%, left atrial diameter was 47mm, E/e' was 17.5, and IVCv was 4.5cm/sec; mean tricuspid regurgitation velocity was 2.6m/sec. Regarding laboratory data, the median plasma B-type natriuretic peptide level was 185pg/mL. Thirty-four events occurred (15 deaths, 19 unplanned hospitalizations due to HF) within the first year. In multivariate Cox proportional hazards analyses, IVCv was significantly associated with outcomes (hazard ratio .68, 95% confidence interval .50-.89, p=.0095), independent of general characteristics, echocardiographic measures and pertinent laboratory parameters. LV IVCv was independently associated with 1-year outcomes in patients with HFpEF.