Infarcted Left Ventricle Research Articles

Bioelectronic block of stellate ganglia mitigates pacing-induced heterogeneous release of catecholamine and neuropeptide Y in the infarcted pig heart.

The sympathetic nervous system modulates cardiac contractile and electrophysiological function and contributes to adverse remodelling following myocardial infarction (MI). Axonal modulation therapy (AMT), directed at the sympathetic chain, blocks efferent sympathetic outflow to the heart and is a strategy to transiently and controllably mitigate chronic MI-associated sympatho-excitation. In porcine models, we evaluated scalable AMT, directed at the paravertebral chain, in blocking reflex-mediated pacing-induced sympatho-excitation post-MI. The level of sympatho-excitation was assessed by dynamic interstitial measurement of noradrenaline (NA) and neuropeptide Y (NPY). In anaesthetized normal (n=5) and age-matched pigs 6weeks post-MI induction (n=10), we electrically stimulated the right sympathetic chain and determined levels of direct current block applied at the T1-T2 level sufficient to reduce the evoked changes in heart rate and/or contractility by 25-75%. Reflex-mediated neural release of NA and NPY into the interstitial space during programmed pacing (PP) was assessed using fast-scanning cyclic voltammetry and capacitive immunoprobes. Normal animals demonstrated homogeneous NA and NPY release profiles during PP. In contrast, for MI animals PP evoked differential NA and NPY release in remote and MI border zones of the left ventricle. Right-sided AMT mitigated NA and NPY pacing-induced release in the remote left ventricle with a positive correlation to increasing AMT levels. Pacing-induced NA and NPY release in the MI border zone was not mitigated by AMT. Differential effects of AMT on NA and NPY may underlie the anti-arrhythmic effects of partial stellate ganglion block in the setting of chronic MI. KEY POINTS: Programmed cardiac pacing evokes homogeneous noradrenaline (NA) and neuropeptide Y (NPY) release in equivalent areas (e.g. medial and lateral aspects) of the normal left ventricle. Programmed cardiac pacing evokes differential NA and NPY release in remote and border zones of the infarcted left ventricle. Axonal modulation therapy (AMT), using a graded direct current block applied to the stellate ganglia, can proportionally modulate cardiac sympathetic reflexes. Unilateral AMT mitigates NA and NPY release in remote left ventricular tissue, with release negativelycorrelated to increasing AMT levels. Heterogeneities in NA and NPY between the border and remote tissues are reduced by progressive AMT.

Abstract We065: Sex Differences in Autoimmune Signatures After Myocardial Infarction in Mice

Introduction: Myocardial infarction (MI) is caused by ischemic injury to the left ventricle (LV), leading to an inflammatory response, scar formation, and loss of LV function. The role of the autoimmune (AI) response during chronic MI, such as B cell activation and autoantibody production, is not well understood. As AI disease is much more prevalent in females, we hypothesized that female mice are more susceptible to MI-induced development of AI signatures. Methods: Permanent MI was induced by left coronary artery ligation in adult male and female C57BL/6J mice for 7, 28, or 56 days. LV function was tracked using echocardiography (VEVO 3100). Cytokines were measured by qPCR. LV IgG and IgM antibody deposition was measured by immunofluorescence. Plasma IgG and IgM were measured by ELISA, and plasma autoantibodies (AABs) (IgG and IgM subclasses) were measured with an autoantigen (AAN) array. Results: In both sexes, MI led to progressive LV hypertrophy, dilation, and wall thinning. MI increased spleen mass in D7, 28, and 56 females, but decreased spleen mass in D28 and 56 males. LV infarct cytokines (IL-1β, IL-6, IL-18, IFN-γ, TNF, CCL2, IL-10) were increased at D7, while IL-6 and IL-18 remained elevated at D28 and 56 to a higher degree in females. Several cytokines in the remote LV were increased in females relative to males, including TNF, IL-6, CCL2, and IL-18. Splenic cytokines were also differentially expressed between sexes, with IL-1β, IL-12a, IL-10, IFN-γ, IL-18, CCL2, and IL-4 increased in females at several time points. Infarct IgG and IgM deposition occurred in both sexes, but to a higher degree in females. Remote IgG and IgM deposition occurred at D56 in both sexes. For plasma AABs, we detected 34 AANs against which IgG AABs were significantly elevated (p<0.05) at D56 in females vs 9 in males, and 30 IgM AABs vs 1 in males. Of note, anti-IL-6 IgM AABs were elevated in D56 females (9.8±0.8-fold), likely due to persistently elevated IL-6 in the female infarct and remote LV vs males. Total levels of plasma IgM were increased only in females at D56 (1.79±0.15-fold). Conclusions: MI promotes development of AI signatures which is exacerbated in females, including increased spleen mass, LV and splenic cytokines, LV infarct and remote IgG and IgM antibody deposition, increased plasma IgG and IgM AABs, and increased total levels of plasma IgM. Targeting the AI response may be a viable option for treating chronic MI outcomes, particularly in females.

Tissue-Based Predictors of Impaired Right Ventricular Strain in Coronary Artery Disease: A Multicenter Stress Perfusion Study.

Right ventricular (RV) dysfunction is known to impact prognosis, but its determinants in coronary artery disease are poorly understood. Stress cardiac magnetic resonance (CMR) has been used to assess ischemia and infarction in relation to the left ventricle (LV); the impact of myocardial tissue properties on RV function is unknown. Vasodilator stress CMR was performed in patients with known coronary artery disease at 7 sites between May 2005 and October 2018. Myocardial infarction was identified on late gadolinium enhancement-CMR, and infarct transmurality was graded on a per-segment basis. Ischemia was assessed on stress CMR based on first-pass perfusion and localized by using segment partitions corresponding to cine and late gadolinium enhancement analyses. RV function was evaluated by CMR-feature tracking for primary analysis with a global longitudinal strain threshold of 20% used to define impaired RV strain (RVIS); secondary functional analysis via RV ejection fraction was also performed. A total of 2604 patients were studied, among whom RVIS was present in 461 patients (18%). The presence and magnitude of RVIS were strongly associated with LV dysfunction, irrespective of whether measured by LV ejection fraction or wall motion score (P<0.001 for all). Regarding tissue substrate, regions of ischemic and dysfunctional myocardium (ie, hibernating myocardium) and infarct size were each independently associated with RVIS (both P<0.001). During follow-up (median, 4.62 [interquartile range, 2.15-7.67] years), 555 deaths (21%) occurred. Kaplan-Meier analysis for patients stratified by presence and magnitude of RV dysfunction by global longitudinal strain and RV ejection fraction each demonstrated strong prognostic utility for all-cause mortality (P<0.001). RVIS conferred increased mortality risk (hazard ratio, 1.35 [95% CI, 1.11-1.66]; P=0.003) even after controlling for LV function, infarction, and ischemia. RVIS in patients with known coronary artery disease is associated with potentially reversible LV processes, including LV functional impairment due to ischemic and predominantly viable myocardium, which confers increased mortality risk independent of LV function and tissue substrate.

Sex Differences in Autoimmune Signatures After Myocardial Infarction in Mice

Myocardial infarction (MI) is caused by ischemic injury to the left ventricle (LV), leading to an acute inflammatory response, scar formation, and loss of LV function. The role of the antibody-mediated response and autoimmune (AI) development during MI is not well understood. AI disease is highly prevalent in females, which increases risk of MI and worsens MI outcomes. Thus, we hypothesized that females would exhibit increased susceptibility to MI-induced development of AI signatures, including B cell activation and autoantibody (AAB) production. Permanent MI was induced by left coronary artery ligation in adult male and female C57BL/6J mice, which were followed for 7, 28, or 56 days, using no MI (D0) as controls. LV function was tracked using echocardiography (VEVO 3100). LV infarct cytokines were measured by qPCR. LV infarct and blood leukocytes were measured by flow cytometry. LV IgG and IgM antibody deposition was measured by immunofluorescence. Plasma AABs (IgG and IgM subclasses) were measured with an autoantigen (AAN) microarray (128 AANs). In both sexes, MI led to progressive LV hypertrophy, increased end-diastolic diameter and volume, anterior/posterior wall thinning, and decreased ejection fraction. Survival was significantly higher in females for each time point (100% vs 50% at D7, 83% vs 57% at D28, 94% vs 39% at D56). MI increased spleen mass/tibia length in D7, 28, and 56 females, but decreased spleen mass in D28 and 56 males. LV inflammatory cytokines (IL-1β, IL-6, IL-18, IFN-γ, TNF, CCL2, IL-10) were increased at D7. In both sexes, IL-6 and IL-18 remained elevated at D28 and 56. Blood and LV myeloid cells were increased at D7 in both sexes, while B and T cells were decreased. At D28, myeloid cells returned to D0 levels; LV activated B cells (CD80+) and T cells (CD3+) were increased. At D56, only B cells remained elevated in the LV. IgG deposition was increased in the female LV at D7 (14.1±1.2% area fraction vs 6.3±1.5% D0) and further at D28 (40.4±3.6%), but only at D28 in males (20.4±4.0% vs 3.1±0.7% D0). Both sexes exhibited increased LV IgM at D7 and 28, however, the IgM response at D7 was higher in females (21.1±2.8% vs 8.3±1.6% in males). In plasma, MI increased AABs against several AANs (p&lt;0.05 vs D0). Compared to D0, D7 females had elevated IgG AABs 1 AAN (dsDNA, a classical AI marker) vs 0 for males, and elevated IgM AABs against 4 different AANs versus 1 for males. D28 females had elevated IgG AABs against 1 AAN vs 4 for males, and elevated IgM AABs against 5 AANs vs 0 in males. D56 females had elevated IgG AABs against 34 AANs vs 9 in males, and elevated IgM AABs against 30 AANs versus 1 for males. For both IgG and IgM AABs in D56 females, several were against AANs highly expressed in the heart, including ACE2, mitochondrion, and myosin. Furthermore, D56 female IgM AABs were increased against IL-6 (9.8±0.8 fold change), which as mentioned earlier, remained elevated in the LV at all post-MI time points. In summary, MI promotes development of AI signatures, including LV B and T cell activation, IgG and IgM antibody deposition, and increased circulating AABs, which is exacerbated in females. NHLBI R01 HL166737 (Mouton), AHA Career Development Award CDA856365 (Mouton), NIH/NHLBI R00 HL146888 (Taylor), U54 HL169191 (Taylor), NIGMS P20 GM104357 (Hall), P30 GM149404 (Hall), U54 GM115428 (Hall), NHLBI R01 HL1630376 (da Silva), NIDDK R01 DK121411 (do Carmo), AHA Postdoctoral Fellowship 835218 (Omoto). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Clinical significance of R-wave amplitude in lead V1 and inferobasal myocardial infarction in patients with inferior wall myocardial infarction.

To assess electrocardiogram (ECG) for risk stratification in inferior ST-elevation myocardial infarction (STEMI) patients within 24 h. Three hundred thirty-four patients were divided into four ECG-based groups: Group A: R V1 <0.3 mV with ST-segment elevation (ST↑) V7-V9, Group B: R V1 <0.3 mV without ST↑ V7-V9, Group C: R V1 ≥0.3 mV with ST↑ V7-V9, and Group D: R V1 ≥0.3 mV without ST↑ V7-V9. Group A demonstrated the longest QRS duration, followed by Groups B, C, and D. ECG signs for right ventricle (RV) infarction were more common in Groups A and B (p < .01). ST elevation in V6, indicative of left ventricle (LV) lateral injury, was more higher in Group C than in Group A, while the ∑ST↑ V3R + V4R + V5R, representing RV infarction, showed the opposite trend (p < .05). The estimated LV infarct size from ECG was similar between Groups A and C, yet Group A had higher creatine kinase MB isoform (CK-MB; p < .05). Cardiac troponin I (cTNI) was higher in Groups A and C than in B and D (p < .05 and p = .16, respectively). NT-proBNP decreased across groups (p = .20), with the highest left ventricular ejection fraction (LVEF) observed in Group D (p < .05). Group A notably demonstrated more cardiac dysfunction within 4 h post-onset. For inferior STEMI patients, concurrent R V1 <0.3 mV with ST↑ V7-V9 suggests prolonged ventricular activation and notable myocardial damage. RV infarction's dominance over LV lateral injury might explain these observations.

P222 POSTINFARCT CARDIAC FREE WALL RUPTURE DETECTED BY CARDIAC CT

Abstract A 57–years–old man with a history of smoke and hypertension was transferred to our unit with chest pain and dyspnoea, lasting few days. Electrocardiography revealed the presence of ST elevation in the infero–lateral leads with Q waves and Transthoracic Echocardiographic Study revealed a normal dimension left ventricle with infero–postero–lateral akinesia, moderately reduced EF (40%) in the absence of significant valve disease and an organized pericardial effusion of about one centimetre. In the meantime, the first signs of hemodynamic instability and cardiogenic shock appeared and the ETT revealed the exacerbation of the pericardial effusion. So we did an emergency coronary angiography that revealed a calcified three–vessel disease with occlusion of the middle segment of Cx. Because of the worsening of the cardiogenic shock we used the aortic balloon pump to improve the hemodynamic instability. The concomitant presence of signs of late infarction, pericardial effusion and cardiogenic shock make us suspect a myocardial rupture so we did a cardiac computed tomography (CT ) scan that was suggestive for a cardiac wall rupture within the infarcted left ventricle. The patient was urgently transported to the cardiac surgery room where the patch of inferior wall was performed and then was transferred to the Intensive Care Unit. After the surgery, a residual of pericardial effusion persisted without hemodynamic significant and the revascularization was planned one month after discharge. Heart rupture represents a mechanical complication of MI that we have to suspect every time we find signs of myocardial infarction and pericardial effusion that degenerate into cardiogenic shock. Although it occurs in a very limited number of cases, the postinfarct cardiac free wall rupture is characterized by a poor prognosis and cardiac Computed Tomography provides primary information for the diagnosis.

Myofibroblast Ccn3 is regulated by Yap and Wwtr1 and contributes to adverse cardiac outcomes.

While Yap and Wwtr1 regulate resident cardiac fibroblast to myofibroblast differentiation following cardiac injury, their role specifically in activated myofibroblasts remains unexplored. We assessed the pathophysiological and cellular consequence of genetic depletion of Yap alone (Yap fl/fl ;Postn MCM ) or Yap and Wwtr1 (Yap fl/fl ;Wwtr1 fl/+ ;Postn MCM ) in adult mouse myofibroblasts following myocardial infarction and identify and validate novel downstream factors specifically in cardiac myofibroblasts that mediate pathological remodeling. Following myocardial infarction, depletion of Yap in myofibroblasts had minimal effect on heart function while depletion of Yap/Wwtr1 resulted in smaller scars, reduced interstitial fibrosis, and improved ejection fraction and fractional shortening. Single cell RNA sequencing of interstitial cardiac cells 7 days post infarction showed suppression of pro-fibrotic genes in fibroblasts derived from Yap fl/fl ,Wwtr1 fl/+ ;Postn MCM hearts. In vivo myofibroblast depletion of Yap/Wwtr1 as well in vitro knockdown of Yap/Wwtr1 dramatically decreased RNA and protein expression of the matricellular factor Ccn3. Administration of recombinant CCN3 to adult mice following myocardial infarction remarkably aggravated cardiac function and scarring. CCN3 administration drove myocardial gene expression of pro-fibrotic genes in infarcted left ventricles implicating CCN3 as a novel driver of cardiac fibrotic processes following myocardial infarction. Yap/Wwtr1 depletion in myofibroblasts attenuates fibrosis and significantly improves cardiac outcomes after myocardial infarction and we identify Ccn3 as a factor downstream of Yap/Wwtr1 that contributes to adverse cardiac remodeling post MI. Myofibroblast expression of Yap, Wwtr1, and Ccn3 could be further explored as potential therapeutic targets for modulating adverse cardiac remodeling post injury.

Relationship of Microvascular Obstruction with Global and Regional Myocardial Function Determined by Cardiac Magnetic Resonance after ST-Segment Elevation Myocardial Infarction

ObjectiveTo investigate the impact of microvascular obstruction (MVO) on the global and regional myocardial function by cardiac magnetic resonance feature-tracking (CMR-FT) in ST-segment-elevation myocardial infarction (STEMI) patients after percutaneous coronary intervention. MethodsConsecutive acute STEMI patients who underwent cardiac magnetic resonance imaging 1 - 7 days after successful reperfusion by percutaneous coronary intervention treatment were included in this retrospective study. Based on the presence or absence of MVO on late gadolinium enhancement images, patients were divided into groups with MVO and without MVO. The infarct zone, adjacent zone, and remote zone were determined based on a myocardial 16-segment model. The radial strain (RS), circumferential strain (CS), and longitudinal strain (LS) of the global left ventricle (LV) and the infarct, adjacent, and remote zones were measured by CMR-FT from cine images and compared between patients with and without MVO using independent-samples t-test. Logistic regression analysis was used to assess the association of MVO with the impaired LV function. ResultsA total of 157 STEMI patients (mean age 56.66 ± 11.38 years) were enrolled. MVO was detected in 37.58% (59/157) of STEMI patients, and the mean size of MVO was 3.00 ±3.76 mL. Compared with patients without MVO (n = 98), the MVO group had significantly reduced LV global RS (t = −4.30, P < 0.001), global CS (t = 4.99, P < 0.001), and global LS (t = 3.51, P = 0.001). The RS and CS of the infarct zone in patients with MVO were significantly reduced (t = −3.38, P = 0.001; t = 2.64, P = 0.01; respectively) and the infarct size was significantly larger (t = 8.37, P < 0.001) than that of patients without MVO. The presence of LV MVO [OR = 4.10, 95%CI: 2.05 – 8.19, P < 0.001) and its size [OR = 1.38, 95% CI: 1.10–1.72, P=0.01], along with the heart rate and LV infarct size were significantly associated with impaired LV global CS in univariable Logistic regression analysis, while only heart rate (OR=1.08, 95%CI: 1.03 – 1.13, P=0.001) and LV infarct size (OR=1.10, 95%CI: 1.03 - 1.16, P=0.003) were independent influencing factors for the impaired LV global CS in multivariable Logistic regression analysis. ConclusionThe infarct size was larger in STEMI patients with MVO, and MVO deteriorates the global and regional LV myocardial function.

Arachidonate 5-lipoxygenase is essential for biosynthesis of specialized pro-resolving mediators and cardiac repair in heart failure.

Arachidonate 5-lipoxygenase (ALOX5)-derived leukotrienes are primary signals of leukocyte activation and inflammation in response to ischemic cardiac injury (MI; myocardial infarction). Using risk-free male C57BL/6J and ALOX5-null mice (8-12 wk), we quantitated leukocytes and ALOX5-derived bioactive lipids of the infarcted left ventricle (LV) and spleen to measure the physiological inflammation and cardiac repair. Our results showed that ALOX5 endogenously generates specialized pro-resolving mediators (SPMs) that facilitate cardiac repair post-MI. Deficiency of ALOX5 leads to increase in cyclooxygenase gene expression, 6-keto prostaglandin F1α, and delayed neutrophil clearance with signs of unresolved inflammation post-MI. Consequently, ALOX5 deficiency impaired the resolution of inflammation and cardiac repair, including increased myocardium rupture post-MI in acute heart failure. On-time ALOX5 activation is critical for leukocyte clearance from the infarcted heart, indicating an essential role of ALOX5 in the resolution of inflammation. In addition, to balance the inflammatory responses, ALOX5 is also necessary for fibroblast signaling, as the ALOX5-deficient fibroblast are prone to fibroblast-to-myofibroblast differentiation leading to defective scar formation in post-MI cardiac repair. Consistent with these findings, ALOX5-null mice showed an overly inflammatory response, defective fibrotic signaling, and unresolved inflammation. These findings are indicative of a critical role of ALOX5 in myocardium healing, inflammation-resolution signaling, cardiac repair, and fibroblast pathophysiology.NEW & NOTEWORTHY Arachidonate 5-lipoxygenase (ALOX5) is critical in synthesizing specialized pro-resolving mediators that facilitate cardiac repair after cardiac injury. Thus, ALOX5 orchestrates the overlapping phases of inflammation and resolution to facilitate myocardium healing in cardiac repair postmyocardial infarction.

Short-Term Blockade of Pro-Inflammatory Alarmin S100A9 Favorably Modulates Left Ventricle Proteome and Related Signaling Pathways Involved in Post-Myocardial Infarction Recovery.

Prognosis after myocardial infarction (MI) varies greatly depending on the extent of damaged area and the management of biological processes during recovery. Reportedly, the inhibition of the pro-inflammatory S100A9 reduces myocardial damage after MI. We hypothesize that a S100A9 blockade induces changes of major signaling pathways implicated in post-MI healing. Mass spectrometry-based proteomics and gene analyses of infarcted mice left ventricle were performed. The S100A9 blocker (ABR-23890) was given for 3 days after coronary ligation. At 3 and 7 days post-MI, ventricle samples were analyzed versus control and Sham-operated mice. Blockade of S100A9 modulated the expressed proteins involved in five biological processes: leukocyte cell–cell adhesion, regulation of the muscle cell apoptotic process, regulation of the intrinsic apoptotic signaling pathway, sarcomere organization and cardiac muscle hypertrophy. The blocker induced regulation of 36 proteins interacting with or targeted by the cellular tumor antigen p53, prevented myocardial compensatory hypertrophy, and reduced cardiac markers of post-ischemic stress. The blockade effect was prominent at day 7 post-MI when the quantitative features of the ventricle proteome were closer to controls. Blockade of S100A9 restores key biological processes altered post-MI. These processes could be valuable new pharmacological targets for the treatment of ischemic heart. Mass spectrometry data are available via ProteomeXchange with identifier PXD033683.

CA-534-01 PULSED FIELD ABLATION COMPARED TO RADIOFREQUENCY ABLATION OF LEFT VENTRICULAR MYOCARDIUM IN A SWINE INFARCT MODEL

There is limited data on use of pulsed field ablation (PFA) in the left ventricle (LV), particularly in the presence of myocardial scar To evaluate the lesion characteristics of PFA and radiofrequency energy (RFA) in healthy and infarcted LV myocardium 10 swine were included: 8 underwent 120min LAD balloon occlusion myocardial infarction and were survived for 6-8 weeks; 2 were healthy controls. PFA and standard RFA was delivered to the LV endocardium in healthy myocardium or scar identified with electroanatomic mapping. Bipolar, biphasic PFA was delivered at 1800 to 2000V for 2.5secs x 4 applications/site using 2 different catheters: linear quadripolar (LINEAR) or multi-spline 8-pole catheter (BASKET). Irrigated RF energy was delivered from 35W-50W to achieve >10 ohm impedance drop. Detailed histologic measurements of ablation depth were performed. In the PFA group, 21 lesions were delivered to healthy LV and 20 to scar, all without complications. There was no significant difference in histologic lesion depth in healthy myocardium or scar between LINEAR vs. BASKET PFA catheters (Figure A). In the RF group, 19 lesions were delivered to healthy LV and 8 to scar. Maximal lesion depth for PFA and RFA were similar in healthy tissue, however lesion depth was greater for PFA than RFA in scar (Figure B, 6.1±1.7 vs 3.8±1.7 mm; P=0.005). There was no vascular injury observed with PFA, however RFA led to adventitial edema and thrombosis. PFA allows rapid, safe and effective ablation of surviving islands of myocardium within infarcted LV substrate. Lesion depth in myocardial scar is greater for PFA than RFA. This technology holds promise for treating infarct-related ventricular tachycardia in humans.

Acute-Phase Inflammatory Reaction Predicts CMR Myocardial Scar Pattern and 2-Year Mortality in STEMI Patients Undergoing Primary PCI.

(1) Background: The inflammatory response following MI plays an important role in the healing, scar formation, and left ventricle (LV) remodeling. Cardiac magnetic resonance (CMR) imaging can accurately quantify the extent of myocardial scarring. The study aimed to investigate: (a) the relationship between acute inflammatory response and the CMR parameters of the scarring extent, and (b) the predictive power of inflammatory biomarkers and myocardial scarring for 2-year mortality. (2) Methods: The study included 202 STEMI patients, who underwent pPCI. Serum hs-CRP, IL-6, P-selectin, E-selectin, I-CAM, and V-CAM levels were determined at admission, and hs-CRP on the fifth day. Patients underwent LGE-CMR after 1 month, for LV volumes, ejection fraction (EF), infarct size (IS), and transmurality. Subjects were divided into tertiles according to the IS, and 2-year all-cause mortality was determined. (3) Results: IL-6 was associated with IS (r = 0.324, p = 0.01), increased transmurality index (r = 0.3, p = 0.01), and lower LVEF (r = −0.3, p = 0.02). Admission hs-CRP levels were not associated with IS, transmurality, or mortality, while hs-CRP at day 5 was a significant predictor for IS (AUC = 0.635, p = 0.05) as well as IL-6 levels (AUC = 0.685, p < 0.001). Mortality was significantly higher in the upper IS tertiles (6% vs. 8.7% vs. 24.52%, p = 0.005). IS was a significant predictor of 2-year mortality (AUC = 0.673, p = 0.002), with a cut-off value of 28.81 g, as well as high transmurality (AUC = 0.641, p = 0.013), with a cut off value of 18.38 g. (4) Conclusions: The serum levels of IL-6 and day-5 hs-CRP predict IS and transmurality, and day-5 hs-CRP levels are independent predictors of 2-year mortality in STEMI patients treated with pPCI. The CMR pattern of myocardial scarring after 1 month, as expressed by the magnitude of IS and transmurality, is a significant predictor for 2-year mortality after revascularized STEMI.

Levosimendan Postconditioning Attenuates Cardiomyocyte Apoptosis after Myocardial Infarction.

Background Levosimendan preconditioning has been shown to attenuate myocardial apoptosis in animal models. However, protective effects of levosimendan postconditioning against myocardial apoptosis following myocardial infarction (MI) have not been evaluated. Therefore, we investigated the effects of levosimendan postconditioning on myocardial apoptosis in MI rat models. Methods In an anoxia/reoxygenation (A/R) model, H9c2 cells were pretreated with or without levosimendan postconditioning after which their apoptosis rates were assessed by flow cytometry, RT-qPCR, and western blot analyses. Then, postconditioning was performed with or without levosimendan in MI rat models. Myocardiocyte apoptosis was evaluated by echocardiography, TTC staining, TUNEL staining, immunohistochemical staining, RT-qPCR, and western blot analysis. Results Levosimendan postconditioning inhibited H9c2 cell apoptosis in A/R models by elevating Bcl-2 while suppressing Caspase-3 and Bax at both mRNA and protein levels. Moreover, it improved cardiac functions and reduced the left ventricle infarction area in MI rat models. Compared to the MI control group, cardiomyocyte apoptosis rates in the levosimendan postconditioning group were low. The reduced cardiomyocyte apoptosis rates were associated with downregulation of Bax and Caspase-3 as well as with upregulation of Bcl-2 at mRNA and protein levels. Conclusions Levosimendan postconditioning of MI rat models protected against cardiomyocyte apoptosis, implying that it is a potential strategy for preventing cardiomyocyte apoptosis in the treatment of cardiac dysfunction following MI.

Стан систолічної функції та діастолічного наповнення міокарда у хворих з інфарктом міокарда правого шлуночка на фоні Q-інфаркту міокарда лівого шлуночка протягом 6 місяців спостереження

Актуальність. Постінфарктне ремоделювання внаслідок інфаркту міокарда (ІМ) правого шлуночка (ПШ) асоціюється з погіршенням прогнозу хворих. Актуальним є визначення зв’язку між ступенем порушень систолічної та діастолічної функції лівого шлуночка (ЛШ) та ПШ і прогресуванням серцевої недостатності (СН) у хворих з ІМ ПШ на фоні Q-ІМ ЛШ. Мета. Визначення особливостей динаміки постінфарктного ремоделювання та стану діастолічної дисфункції міокарда (ДДМ) ЛШ та ПШ у хворих з ІМ ПШ на фоні Q-ІМ ЛШ протягом 6 місяців спостереження та їх зв’язок з прогресуванням СН. Матеріали та методи. Обстежено 309 хворих з Q-ІМ віком 65,50 ± 4,42 року: 1-ша група — 155 пацієнтів з ІМ ПШ на фоні Q-ІМ задньої стінки (ЗС) ЛШ; 2-га група — 53 особи з ІМ ПШ на фоні циркулярного Q-ІМ ЛШ; 3-тя група — 101 хворий з Q-ІМ ЗС ЛШ — група контролю. Ехокардіоскопію з допплерографією проводили на 4–5-ту добу та через 6 місяців після ІМ. Результати. У хворих з ІМ ПШ у гострому періоді відзначали вірогідно більшу частоту псевдонормального та рестриктивного типу ДДМ ЛШ та ПШ (p &lt; 0,05), які формувались на фоні значної дилатації ЛШ, ЛП, ПП та ПШ (p &lt; 0,05), зниження систолічної функції ЛШ та ПШ і підвищення систолічного тиску в легеневій артерії (p &lt; 0,05), що асоціювалось з високою частотою фатальних аритмій (p &lt; 0,05) та вираженими проявами гострої СН у вигляді Killip III та кардіогенного шоку порівняно з групою контролю (p &lt; 0,05). Через 6 місяців відзначалось покращення показників систолічної функції ЛШ і ПШ та показників діастолічного наповнення з ознаками нормалізації та переважанням релаксаційного типу ДДМ ЛШ та ПШ (p &lt; 0,05), проте у пацієнтів після ІМ ПШ визначались більш тяжкі прояви СН у вигляді вірогідно більшої кількості хворих з СН ІІА стадії та функцінальним класом ІІІ (за NYHA) (p &lt; 0,05) порівняно з групою контролю. Висновки. ІМ ПШ на фоні Q-ІМ ЛШ супроводжується більш глибокими порушеннями систолічної функції та діастолічного наповнення ЛШ і ПШ та асоціюється з високою частотою фатальних аритмій, набряку легень та кардіогенного шоку в гострому періоді, а також із прогресуванням СН протягом 6 місяців спостереження.

Prognostic value of divergent pattern detection by 99mTc-sestamibi gated SPECT in patients with anterior acute myocardial infarction

PurposeIn gated myocardial perfusion SPECT, apical remodeling may be identified by the presence of a divergent pattern (DP) of the left ventricle (LV). Methods and ResultsWe examined 150 anterior ST-elevation myocardial infarction (STEMI) patients, all successfully treated with primary percutaneous coronary interventions (PCI). Perfusion gated-SPECT to measure infarct size, LV end-diastolic (ED) and end-systolic (ES) volumes and ejection fraction (EF) was acquired before hospital discharge and repeated at 6-month follow-up. DP was observed in 26 patients, who had larger infarct size (28 ± 19% vs. 15.7 ± 17%, P < 0.02), and lower EF (33 ± 7% vs. 41 ± 10%, P < 0.001) than patients without DP. At follow-up, DP patients had significantly larger EDV (156 ± 54 vs. 107 ± 44 mL, P < 0.0001), ESV (104 ± 47 vs. 59 ± 36 mL, P < 0.0001) and lower EF (35 ± 12% vs. 48 ± 13%, P < 0.0001). 54% of DP patients developed remodeling at follow-up vs. 12% of those without DP (P < 0.001). During follow up, 7 events in the DP group (27%) and 11 events in patients without DP (9%; P < 0.02) occurred. Kaplan–Meier survival curves showed a worse prognosis for DP patients. ConclusionIn patients with anterior AMI, early DP detection is related to subsequent LV dysfunction, larger infarct size, and worse severity. It is helpful for predicting LV remodeling at short-term follow-up and has prognostic implications.

New score scale for assessing the risk of establishing chronic heart failure with preserved ejection fraction

The aim of the study was to develop a score scale for assessing the high risk of establishing chronic heart failure with preserved ejection fraction (HFpEF), based on echocardiography (EchoCG) evidence.Materials and methods. A clinical and instrumental study of 175 patients, of which 108 (61.7%) women and 67 (38.3%) men, aged 71 [64; 78] years was performed in the 1st City Clinical Hospital in Minsk in 2017–2018. In order to validate the score scale for assessing the risk of HFpEF establishment in 2019–2020 a reproductive clinical and instrumental study of 129 patients was performed at the Minsk Scientific and Practical Center for Surgery, Transplantology and Hematology, of which 55 (42.6%) were men and 74 (57.4%) women aged 65 [58; 70] years. Inclusion criteria: sinus rhythm, essential arterial hypertension, chronic coronary heart disease: atherosclerotic heart disease, past myocardial infarction of left ventricle (LV), after which at least six months have passed, necessary to stabilize the structural and functional parameters of the LV, HFpEF, informed consent of the patient. Exclusion criteria: primary mitral regurgitation, mitral stenosis, mitral valve repair or prosthetics, congenital heart defects, acute and chronic diseases of the kidneys, lungs. EchoCG was performed on ultrasound machines Siemens Acuson S1000 (Germany) and Vivid E9 (GE Healthcare, USA).Results. The developed scale for assessing the risk of establishing HFpEF in a patient with sinus rhythm including the criteria: LV diastolic dysfunction type II – 47 points, deceleration time of peak E of the transmitral blood flow DTE ≤171 ms – 25 points, the speed of early diastolic movement of the septal part of the mitral fibrous ring e'septal ≤7 cm/s – 25 points, LV early diastolic filling index E/е'septal &gt;7.72 – 20 points, index of the end-systolic volume of the left atrium &gt;34.3 ml/m2 – 24 points, has high diagnostic reliability (AUC 0.96, sensitivity (S) 96.6%, specificity (Sp) 83.2%) and reproducibility of results in an examination cohort of patients (AUC 0.99, S 98.8%, Sp 98.0%). A total score &gt; 45 indicates a high probability of HFpEF. If the total score is ≤45, it is recommended to perform 2D Speckle Tracking EchoCG. The leading patho-functional mechanisms for the development of HFpEF are a decrease of LV global systolic longitudinal strain GLSAVG &gt; −18.9% (S 94.9%, Sp 98.0%), GLS of the right ventricle (RV) &gt; −19.9% (S 76.5%, Sp 88.5%), mechanical dispersion with LV mechanical dispersion index &gt; 54.69 ms (S 70.7%, Sp 90.2%), RV mechanical dispersion index &gt; 50.29 msec (S 78.1%, Sp 73.9%) and ventricular dyssynergy with LV global post systolic index &gt;5.59% (S 82.6%, Sp 87.5%), RV global post systolic index &gt; 2.17% (S 84.5%, Sp 69.9%).Conclusions. The use of the developed scale will improve the efficiency of ultrasound imaging of HFpEF.

ELSO Interim Guidelines for Venoarterial Extracorporeal Membrane Oxygenation in Adult Cardiac Patients.

ELSO Interim Guidelines for Venoarterial Extracorporeal Membrane Oxygenation in Adult Cardiac Patients.

Dimethyl fumarate preserves left ventricular infarct integrity following myocardial infarction via modulation of cardiac macrophage and fibroblast oxidative metabolism

Myocardial infarction (MI) is one of the leading causes of mortality and cardiovascular disease worldwide. MI is characterized by a substantial inflammatory response in the infarcted left ventricle (LV), followed by transition of quiescent fibroblasts to active myofibroblasts, which deposit collagen to form the reparative scar. Metabolic shifting between glycolysis and mitochondrial oxidative phosphorylation (OXPHOS) is an important mechanism by which these cell types transition towards reparative phenotypes. Thus, we hypothesized that dimethyl fumarate (DMF), a clinically approved anti-inflammatory agent with metabolic actions, would improve post-MI remodeling via modulation of macrophage and fibroblast metabolism. Adult male C57BL/6J mice were treated with DMF (10 mg/kg) for 3–7 days after MI. DMF attenuated LV infarct and non-infarct wall thinning at 3 and 7 days post-MI, and decreased LV dilation and pulmonary congestion at day 7. DMF improved LV infarct collagen deposition, myofibroblast activation, and angiogenesis at day 7. DMF also decreased pro-inflammatory cytokine expression (Tnf) 3 days after MI, and decreased inflammatory markers in macrophages isolated from the infarcted heart (Hif1a, Il1b). In fibroblasts extracted from the infarcted heart at day 3, RNA-Seq analysis demonstrated that DMF promoted an anti-inflammatory/pro-reparative phenotype. By Seahorse analysis, DMF did not affect glycolysis in either macrophages or fibroblasts at day 3, but enhanced macrophage OXPHOS while impairing fibroblast OXPHOS. Our results indicate that DMF differentially affects macrophage and fibroblast metabolism, and promotes anti-inflammatory/pro-reparative actions. In conclusion, targeting cellular metabolism in the infarcted heart may be a promising therapeutic strategy.

Predictive Value of N-Terminal Prohormone of Brain Natriuretic Peptide in Long-Term Remodeling of the Left Ventricle in Diabetic Patients of Young and Middle Age With Acute Coronary Syndrome After Percutaneous Coronary Intervention

Abstract. Recently, quantitative analysis of the level of the N-terminal prohormone of the brain naturetic peptide (NT-proBNP) has been widely used to diagnose heart failure (HF). A statistically significant correlation was found between the serum NT-proBNP concentration and HF stage. It was found that in patients with high cardiovascular risk, NT-proBNP has the highest predictive value in relation to mortality. In young and middle-aged patients with diabetes mellitus (DM) with myocardial infarction (MI) and stents of an infarct-associated artery, the frequency of unfavorable remodeling (UR) of the left ventricle (LV) in the long-term prognosis was studied. The frequency of atherosclerotic lesions of the coronary arteries (CA) in patients with diabetes in acute coronary syndrome (ACS) was determined, the results of echocardiographic parameters were presented in the follow-up dynamics, the value of serum NT-proBNP in predicting LV UR 12 months after myocardial infarction (MI) was determined.Aim of study. To assess the diagnostic capabilities of NT-proBNP in the long-term prediction of the development of LV infarction in patients with MI with diabetes in young and middle age after percutaneous coronary intervention (PCI).Design. Prospective controlled non-randomized trial. The patients were examined twice: on the first day of ACS after PCI with stenting of infarct-associated coronary artery and 12 months after AMI. The study included 191 patients with ACS with / without ST-segment elevation, who were divided into two groups. The main group included 76 patients with ACS with diabetes mellitus, the comparison group included 115 patients with ACS without diabetes mellitus. Patients in both groups were comparable in age, gender, comorbidity, and complications of AMI. The duration of diabetes was, on average, 6 years (from one to 12 years).Material and methods. All patients underwent electrocardiography, echocardiography, tests for the content of troponin I, NT-proBNP, glycosylated hemoglobin, lipids, determined the level of creatinine in the blood and the glomerular filtration rate according to the Modification of diet in renal disease (MDRD). All patients were examined twice: on the first day of ACS after PCI with stenting of infarct-associated coronary artery and 12 months later.Results. In 69% of diabetic patients with anterior myocardial infarction and in 63% of patients with posterolateral MI 12 months after PCI, signs of LV inferiority were revealed in the form of an increase in the indices of end-diastolic and systolic volumes of the LV and low ejection fraction (≤45%). In patients without diabetes, these figures were 18% and 31%, respectively. High concentrations of NT-proBNP on the first day of myocardial infarction after PCI were of the greatest value in the diagnosis and prognosis of LV UR after 12 months.Conclusion. The NT-proBNP level of more than 776 pg/ml on the first day after PCI is an indicator of an unfavorable long-term prognosis in patients with young and middle-aged diabetes in terms of the development of LV systolic dysfunction.

Biophysical and Lipidomic Biomarkers of Cardiac Remodeling Post-Myocardial Infarction in Humans.

Few studies have analyzed the potential of biophysical parameters as markers of cardiac remodeling post-myocardial infarction (MI), particularly in human hearts. Fourier transform infrared spectroscopy (FTIR) illustrates the overall changes in proteins, nucleic acids and lipids in a single signature. The aim of this work was to define the FTIR and lipidomic pattern for human left ventricular remodeling post-MI. A total of nine explanted hearts from ischemic cardiomyopathy patients were collected. Samples from the right ventricle (RV), left ventricle (LV) and infarcted left ventricle (LV INF) were subjected to biophysical (FTIR and differential scanning calorimetry, DSC) and lipidomic (liquid chromatography–high-resolution mass spectrometry, LC–HRMS) studies. FTIR evidenced deep alterations in the myofibers, extracellular matrix proteins, and the hydric response of the LV INF compared to the RV or LV from the same subject. The lipid and esterified lipid FTIR bands were enhanced in LV INF, and both lipid indicators were tightly and positively correlated with remodeling markers such as collagen, lactate, polysaccharides, and glycogen in these samples. Lipidomic analysis revealed an increase in several species of sphingomyelin (SM), hexosylceramide (HexCer), and cholesteryl esters combined with a decrease in glycerophospholipids in the infarcted tissue. Our results validate FTIR indicators and several species of lipids as useful markers of left ventricular remodeling post-MI in humans.