Myocardial Layers Research Articles

Changes in myocardial perfusion after coronary sinus reducer implantation for refractory angina - assessment using fully automated quantitative stress perfusion cardiac MRI

Abstract Introduction Previous reports show angina improvement after Coronary Sinus Reducer (CSR) implantation [1,2]. However, the mechanistic basis remains unconfirmed. Preliminary studies using semi-quantitative metrics derived from stress perfusion cardiac MRI (CMR), have suggested improved myocardial perfusion particularly in ischaemic segments [3]. To date, assessment by fully automated quantitative myocardial perfusion CMR has not been reported. Purpose To assess the effect of CSR implantation on quantitative regional myocardial blood flow in patients with refractory angina and advanced coronary artery disease (CAD). Methods Prospective cohort study of patients undergoing CSR implantation. CMR was performed at baseline and median 7 months follow-up. Automated segmentation into a 16-segment American Heart Association model was performed to quantify segmental rest and stress myocardial blood flow (MBF, ml/min/g) and myocardial perfusion reserve (MPR). Rest MBF was corrected for heart rate by dividing by the scan heart rate and multiplying by the mean resting heart rate among all subjects. Wilcoxon matched-pairs sign rank tests were used to compare paired global and segmental perfusion values. A linear mixed-effects model with random slopes and intercepts was used to assess the relationship between baseline segmental MPR and associated change in MPR (ΔMPR) after CSR implantation. Results 12 patients (10M:2F; mean age 67) were included. Median Canadian Cardiovascular Society class was 3. Globally, there was no change in rest (P=0.90), stress MBF (P=0.34) or MPR (P=0.72) from baseline to follow-up. However, ΔMPR was related to the degree of baseline ischaemia (panel A). Segments with baseline MPR<2.45 increased in MPR whereas segments with baseline MPR ≥2.45 experienced a decrease (P=0.003, conditional R2: 0.81). In segments with MPR<2.45 (n=138), median ΔMPR was +0.18 (15.4%; P<0.0001); whereas with MPR≥2.45 (n=52) it was -0.41 (-12.7%; P=0.03; panel B). When assessed by myocardial layer, significant increases in MPR were observed in both subendocardial (+0.19 [15.6%]; P<0.0001) and subepicardial (+0.19 [12.3%]; P<0.0002) segments with baseline MPR< 2.45 (panel C). Conversely, in segments with baseline MPR≥2.45, there was a significant reduction in MPR in the subendocardium (-0.43 [-15.9%]; P=0.04) but not in the subepicardium (-0.36 [-9.90%]; P=0.08; panel D). Conclusion To our knowledge, this is the first study showing changes in quantitative myocardial perfusion after CSR implantation by fully automated inline quantitative perfusion CMR. Our analysis shows a relationship between baseline MPR and change in MPR after CSR implantation, supporting redistribution of perfusion into both subendocardial and subepicardial layers as potential mechanisms of action of CSR. Further studies are needed to confirm these preliminary results.

Role and prognostic relevance of cardiac magnetic resonance imaging in the assessment of left ventricular non-compaction cardiomyopathy: review and meta-analysis

Abstract Background Left ventricular non-compaction (LVNC) is a heterogeneous myocardial disorder characterized by prominent myocardial trabeculation with deep inter-trabecular recesses, thin epicardial layer of compacted myocardium and extensive non-compacted inner muscular layer. Although several diagnostic criteria have been proposed, prediction of major adverse cardiovascular and cerebrovascular events (MACCE) still remains challenging in patients with LVNC. Objectives Objectives of our study were to perform systemic review and meta-analysis of published literature evaluating role and prognostic significance of the late gadolinium enhancement (LGE) in cardiac magnetic resonance imaging (CMR) study, its association with MACCE and characteristics of CMR derived feature-tracking (FT) strain analysis in patients with LVNC. Methods The objectives, literature search strategies, inclusion and exclusion criteria, outcome measurements, and methods of statistical analysis were analyzed according to an established protocol of the cochrane collaboration steps and meta-analysis of observational studies in epidemiology recommendations (MOOSE). Case control studies with evaluated prevalence of LGE in LVNC cardiomyopathy patients with and without MACCE and studies comparing FT strain: left ventricular global longitudinal (LV GLS), global circumferential (GCS) and global radial (GRS) strain between patients with and without LVNC has been included in the analysis. Results A total of 936 papers were collected according to our searching criteria, of those 9 studies including 416 LVNC cardiomyopathy patients with MACCE and 673 LVNC patients without MACCE and with evaluated LGE (including three studies with LVNC and heart failure), also 6 studies including 267 LVNC patients and 283 controls with evaluated FT LV GLS, GCS and GRS (measured in four studies) were selected. LGE was more frequently observed in LVNC patients with MACCE as compared to those without MACCE [RR (95 %CI) 2.52 (1.63 to 3.88); p<0.00001] (Fig.1). FT LV GLS was significantly more affected in LVNC patients compared to controls (St. mean difference (95 %CI): 1.40 (0.69 to 2.11); p<0.00001], as well as GCS and GRS (Fig. 2). Conclusions In patients with LVNC evaluated with CMR, LGE shows association with adverse cardiovascular and cerebrovascular events. CMR deformation indices: FT LV GLS, GCS, and GRS are significantly affected in patients with LVNC as compared to controls. This new CMR technique may be a complementary tool for timely detection and differentiation of LVNC cardiomyopathy and to avoid life threatening adverse events.Figure 1Figure 2

Full cardiac regeneration by MicroRNA and G-actin monomer binding protein

Abstract Myocardial infarction causes massive loss of cardiomyocytes, leading to high mortality rate and heart failure. Cardiac regeneration is thought to have therapeutic potential for myocardial infarction and heart failure. We recently found that Nkx2.5+ cardiac myoblasts exist in declining number in the hearts of postnatal mice. The Nkx2.5+ cardiac myoblasts reactivate after myocardial infarction. They reside mostly in the subepicardium. Using inducible Nkx2.5 enhancer-Cre/ROSA26 reporter double transgenic mice to lineage trace the fate of activated Nkx2.5+ cardiac myoblasts, we documented that the activated Nkx2.5+ cardiac myoblasts proliferate and differentiate into mature cardiomyocyte in vivo. We also documented that Nkx2.5+ cardiac myoblasts originate from the embryonic epicardial cells. Thymosin ß4 is a G-actin monomer binding protein, involved in cell proliferation, migration, and differentiation. We hypothesized that Thymosin ß4 would promote Nkx2.5+ cardiac myoblasts, an embryonic epicardial-derived cells, mobilization and cardiomyogenesis, after myocardial injury. Various microRNAs (miR) have been reported to control cardiac development and promote cardiac regeneration. We have transfected neonatal Nkx2.5 cardiac myoblasts with various microRNAs and found miR-590 markedly promotes cardiomyogenesis capacity of cardiac progenitor cells. We have proved that miR-590 plus Thymosin ß4 (intraperitoneal injection) markedly improved murine cardiac function after myocardial infarction. In the treatment group with miR-590 plus Thymosin ß4 (n=9), LVEF improved from 45% (Day 0) to 77% (Day 7), to 83% (Day 28), to 85% (Day 56) with no LV regional wall motion abnormality and minimal aneurysm formation. In comparison, the control group with miR-mimic plus PBS (n=7), LVEF was 50% (Day 0) to 51% (Day 7), to 56% (Day 28), to 51% (Day 56) with persistent hypokinesia at apex and anterior wall with impaired LV contractility and larger aneurysm was revealed (p<0.001). Heart section of the post-MI mouse receiving miR-590 plus Thymosin ß4 showed minimal fibrosis in the outer layer of myocardium. In contrast, large fibrotic area was noted in the no treatment group. The mice receiving miR-590 plus Thymosin ß4 had a 2-fold increase in survival rate than the control group. Enhanced cardiomyocytes proliferation was documented by phosphorylated histone H3 stain at treated 1-week post-MI heart section. The study applies the results of our recent studies and successfully demonstrated systemic administration of miR-590 plus Thymosin ß4 markedly enhance cardiac repair/ regeneration. We anticipate the result would promote cardiac regeneration in clinical use.

Abstract 13494: Histopathological Analysis Indicates a Significant Role of Myocardial Perfusion Disturbance in Tissue Lesion in Chronic Chagas’ Cardiomyopathy Experimental Model

Introduction: Coronary microvascular perfusion disturbance (MPD) is frequently found in Chronic Chagas' cardiomyopathy (CCC), but its role in tissue lesion and left ventricular dysfunction progression is still unclear. Hypothesis: As MPD is associated with more severe subendocardial myocardial injury, we tested the hypothesis that histopathological changes in subendocardial layer could be quantitatively correlated to MPD in experimental model of CCC in hamsters. Methods: Female Syrian hamsters (n=23) infected with 3.5x10 4 blood trypomastigote forms of T. cruzi ( Y strain ) and their respective controls (n=6) were studied. At 8 months after infection, the animals underwent in vivo high-resolution myocardial rest perfusion scintigraphy with 99m Tc-Sestamibi and transthoracic echocardiography. After euthanasia, the myocardial tissue was processed for quantitative histopathological analysis of mononuclear infiltrate index (MII) using hematoxylin-eosin staining and myocardial fibrosis using picrosirius staining in LV wall layers: subendocardium, mesocardium and subepicardium. Results: Fourteen animals (61%) presented rest MPD. The area of MPD was negatively correlated with LVEF (R=-0.5; p=0.02), and positively correlated with LV diastolic diameter (R=0.83; p<0.01). Animals with MPD exhibited increased extent of myocardial fibrosis in the subendocardial layer (0.67 + 0.18%) as compared to control animals (0.47 + 0.15%), p=0.03. However, the extent of total transmural fibrosis or fibrosis in other myocardial layers were similar among groups. The group with MPD presented higher values of MII in every myocardial layer as compared to controls and animals without MPD. However, only the MII in the subendocardial layer presented positive correlation with the extent of rest MPD (R=0.55, p=0.001). Conclusions: Our results indicate that MPD is significantly correlated with histopathological changes located in the subendocardial layer of LV walls. These results suggest that MPD may act as an amplifying and localizing factor for inflammation and fibrosis, suggesting a relevant role for myocardial hypoperfusion in the mechanisms of myocardial injury in CCC.

An anisotropic electromagnetic hydrogel promotes cardiomyocyte maturation and post-infarction cardiac repair

Effective therapies for myocardial infarction (MI) are essential in lowering associated mortality rates. While hydrogel-based patch therapy has shown promise in improving post-MI cardiac function; it falls short in terms of mature stimulation and lacks the necessary combination of conductive, mechanical, and anisotropic cues for optimal efficacy. In this study, we developed an anisotropic hydrogel by incorporating polydopamine-reduced graphene oxide-ferric oxide (PDA-rGO-Fe3O4) nanohybrids into gelatin methacrylate (GelMA) hydrogels under a direct current-driven magnetic field. Cardiomyocytes (CMs) cultured on anisotropic hydrogels demonstrated oriented growth and exhibited symmetrical contraction-relaxation behaviors, surpassing the performance of cells cultured on pure GelMA and isotropic ones. Moreover, both external electrical and alternating magnetic field stimulations enhanced sarcomere functionality, gap junction protein expression, and electrophysiological activities in CMs within the anisotropic hydrogel group. In an acute MI rat model, the application of the anisotropic hydrogel patch significantly improved cardiac function, mitigated adverse left ventricular (LV) dilation and remodeling, reduced infarct size, increased LV wall thickness, promoted angiomyogenesis, and preserved the structural and connected features between CMs. Overall, our findings highlight the potential of electromagnetic, conductive, and anisotropic GelMA-based hydrogels as scaffolds for mimicking the natural functional myocardium layer and developing effective cardiac patches.

A fusion‐attention swin transformer for cardiac MRI image segmentation

AbstractFor semantic segmentation of cardiac magnetic resonance image (MRI) with low recognition and high background noise, a fusion‐attention Swin Transformer is proposed based on cognitive science and deep learning methods. It has a U‐shaped symmetric encoding–decoding structure with an attention‐based skip connection. The encoder realizes self‐attention for deep feature representation and the decoder up‐samples global features to the corresponding input resolution for pixel‐level segmentation. By introducing a skip connection between the encoder and decoder based on fusion attention, the remote interaction of global information is realized, and the attention to local features and specific channels is enhanced. A public ACDC cardiac MRI image dataset is used for experiments. The segmentation of the left ventricle, right ventricle, and myocardial layer is realized. The method performs well on a small sample dataset, for example, the pixel accuracy obtained by the proposed model is 93.68%, the Dice coefficient is 92.28%, and HD coefficient is 11.18. Compared with the state‐of‐the‐art models, the segmentation precision has been significantly improved, especially for the low recognition and heavily occluded targets.

Investigation of impacts of decellularized heart extracellular matrix and VEGF on cardiomyogenic differentiation of mesenchymal stem cell through Notch/Hedgehog signaling pathways

ObjectiveDecellularization is the process to obtain natural scaffolds with tissue integrity and extracellular matrix components, and recellularization is used to produce tissue-like constructs with specific cell types. In this study, rat bone marrow-derived mesenchymal stem cells (rBM-MSCs) were cultured on decellularized heart extracellular matrix. These cells were then induced to differentiate into cardiomyogenic cells under the stimulatory effect of vascular endothelial growth factor (VEGF) and other chemicals. This study aimed to investigate the effect of the cardiac extracellular matrix and VEGF on cardiomyogenic differentiation in the context of the Notch and Hedgehog signaling pathways. MethodsHeart samples extracted from rats were decellularized by serial application of detergent to remove cells from the tissue, and then recellularized with rBM-MSCs. The recellularized tissue matrices were then analyzed for cardiomyogenesis. Cardiomyogenic differentiation was performed on decellularized heart extracellular matrix (ECM; three-dimensional scaffolds) and culture plates (two-dimensional cell culture system) for 28 days to understand the effects of the heart extracellular matrix. In addition, differentiation was induced with and without the stimulatory effect of VEGF to understand the effect of VEGF on cardiomyogenic differentiation of rBM-MSCs. ResultsImmunofluorescence staining showed that decellularization of the heart was performed effectively and successfully. After decellularization process, the heart extracellular matrix was completely free of cells. It was observed that rBM-MSCs transplanted onto the heart extracellular matrix remained viable and proliferated for 21 days after recellularization. The rBM-MSCs promoted cardiomyogenic differentiation in the conventional differentiation medium but were inversely affected by both VEGF and heart extracellular matrix proteins. Lower expression of connexin43 and cardiac troponin I genes was observed in cells induced by either matrix proteins or VEGF, compared to cells differentiated by chemical agents alone. ConclusionIn this study, we investigated the effect of decellularized heart extracellular matrix and VEGF on cardiomyogenic differentiation of rBM-MSCs. On the decellularized cardiac extracellular matrix, rBM-MSCs maintained their viability by adhering to the matrix and proliferating further. The adhesion of the cells to the matrix also produced a physical stimulus that led to the formation of histological structures resembling myocardial layers. Chemical stimulation of the decellularized heart extracellular matrix and cardiomyogenic differentiation supplements resulted in increased expression of cardiomyogenic biomarkers through modulation of the Notch and Hedgehog signaling pathways.

A novel mutation in the TTN gene resulted in left ventricular noncompaction: a case report and literature review

BackgroundLeft ventricular noncompaction (LVNC) is a specific type of cardiomyopathy characterized by coarse trabeculae and interspersed trabecular crypts within the ventricles. Clinical presentation varies widely and may be nonsignificant or may present with progressive heart failure, malignant arrhythmias, and multiorgan embolism. The mode of inheritance is highly heterogeneous but is most commonly autosomal dominant. The TTN gene encodes titin, which is not only an elastic component of muscle contraction but also mediates multiple signalling pathways in striated muscle cells. In recent years, mutations in the TTN gene have been found to be associated with LVNC, but the exact pathogenesis is still not fully clarified.Case presentationIn this article, we report a case of an adult LVNC patient with a TTN gene variant, c.87857G > A (p. Trp29286*), that has not been reported previously. This 43-year-old adult male was hospitalized repeatedly for heart failure. Echocardiography showed reduced myocardial contractility, dilated left ventricle with many prominent trabeculae, and a loose texture of the left ventricular layer of myocardium with crypt-like changes. During the out-of-hospital follow-up, the patient had no significant signs or symptoms of discomfort.ConclusionThis case report enriches the mutational spectrum of the TTN gene in LVNC and provides a basis for genetic counselling and treatment of this patient. Clinicians should improve their understanding of LVNC, focusing on exploring its pathogenesis and genetic characteristics to provide new directions for future diagnosis and treatment.

The m6A methylation enzyme METTL14 regulates myocardial ischemia/reperfusion injury through the Akt/mTOR signaling pathway.

Herein, we investigated the role of the m6A methylation enzyme METTL14 in regulating myocardial ischemia/reperfusion injury (IR/I) through the Akt/mTOR signaling pathway and related biological mechanisms. Enzyme-linked immunosorbent assay (ELISA) and fluorescence quantitative polymerase chain reaction (qPCR) were performed to detect the m6A mRNA and METTL3, METTL14, WTAP, and KIAA1429 levels in a mouse myocardial IR/I model. An oxygen-glucose deprivation/reperfusion (OGD/R) model was constructed by transfecting neonatal rat cardiomyocytes (NRCM) with METTL14-knockdown lentivirus. METTL14, Bax, and cleaved-caspase3 mRNA expression levels were detected using fluorescence qPCR. Apoptosis was detected using TUNEL staining. After the IR/I surgery following the adeno-associated virus injection, the METTL14 mRNA and apoptosis-related BAX/BCL2 protein expression was detected using fluorescence qPCR and western blotting, respectively. Degree of cell necrosis was detected using an LDH assay. The oxidative stress response of the myocardial tissue was detected, and IL-6 and IL-1β serum levels were detected using ELISAs. The mice injected with METTL14-knockdown AAV9 adeno-associated virus underwent IR/I surgery after the injection of an Akt/mTOR pathway inhibitor (MK2206) into the myocardial layer. Elevated mRNA m6A modification and m6A methyltransferase METTL14 levels were observed in the IR/I-injured mouse heart tissues. METTL14 knockdown significantly inhibited the OGD/R- and IR/I-induced apoptosis and necrosis in cardiac myocytes, inhibited IR/I-induced oxidative stress and inflammatory factor secretion, and activated the Akt/ mTOR pathway in vitro and in vivo. Akt/mTOR pathway inhibition significantly attenuated the alleviating effect of METTL14 knockdown on myocardial IR/I injury-induced apoptosis. Knocking down m6A methylase METTL14 inhibits IR/I-induced myocardial apoptosis and necrosis, inhibits myocardial oxidative stress and secretion of inflammatory cytokines, and activates the Akt/mTOR signaling pathway. Hence, METTL14 regulated myocardial apoptosis and necrosis in mice with IR/I through the Akt/mTOR signaling pathway.

Is Congenital Muscular Mitral-Aortic Discontinuity Another Feature of Obstructive Hypertrophic Cardiomyopathy? A Pathology Validation Study

Hypertrophic cardiomyopathy (HCM) is an inherited myocardial disease at risk of sudden cardiac death and heart failure, even requiring heart transplantation. A “muscular mitral-aortic discontinuity” has been reported during surgery in the obstructive form. We aimed to validate these findings through pathological analysis of HCM heart specimens from the cardiovascular pathology tissue registry. Hearts with septal asymmetric HCM from sudden cardiac death, other causes of death, or heart transplantation were included. Sex-matched and age-matched patients without HCM served as controls. Gross and histologic analysis of the mitral valve (MV) apparatus and the mitral-aortic continuity were performed. Thirty HCM hearts (median age, 29.5 years; 15 men) and 30 controls (median age, 30.5 years; 15 men) were studied. In HCM hearts, a septal bulging was present in 80%, an endocardial fibrous plaque in 63%, a thickening of the anterior MV leaflet in 56.7%, and an anomalous insertion of papillary muscle in 10%. All cases but 1 (97%) revealed a myocardial layer overlapping the mitral-aortic fibrous continuity on the posterior side, corresponding to the left atrial myocardium. A negative correlation between the length of this myocardial layer and the age and the anterior MV leaflet length was found. The length did not differ between HCM and controls.Pathologic study of obstructive HCM hearts does not confirm the existence of a "muscular mitral-aortic discontinuity". An extension of left atrial myocardium, overlapping posteriorly the intervalvular fibrosa, is rather visible, and its length decreases with age, possibly as a consequence of left atrial remodeling. Our study highlights the fundamental role of thorough gross examination and the value of organ retention for further analysis in order to validate new surgical and imaging findings.

The Rare Condition of Left Ventricular Non-Compaction and Reverse Remodeling.

Left ventricular non-compaction (LVNC) is a rare disease defined by morphological criteria, consisting of a two-layered ventricular wall, a thin compacted epicardial layer, and a thick hyper-trabeculated myocardium layer with deep recesses. Controversies still exist regarding whether it is a distinct cardiomyopathy (CM) or a morphological trait of different conditions. This review analyzes data from the literature regarding diagnosis, treatment, and prognosis in LVNC and the current knowledge regarding reverse remodeling in this form of CM. Furthermore, for clear exemplification, we report a case of a 41-year-old male who presented symptoms of heart failure (HF). LVNC CM was suspected at the time of transthoracic echocardiography and was subsequently confirmed upon cardiac magnetic resonance imaging. A favorable remodeling and clinical outcome were registered after including an angiotensin receptor neprilysin inhibitor in the HF treatment. LVNC remains a heterogenous CM, and although a favorable outcome is not commonly encountered, some patients respond well to therapy.

Assessment of left heart dysfunction to predict doxorubicin cardiotoxicity in children with lymphoma.

The objectives of this study were to assess the changes in the left myocardial function after chemotherapy for childhood lymphoma and observe the predictive or monitor value for cancer treatment-related cardiac dysfunction (CTRCD) by speckle-tracking echocardiography. A total of 23 children with histopathological diagnoses of lymphoma were included, with age-matched normal controls. Comparative analysis of clinical serological tests and left heart strain parameters in children with lymphoma, including left ventricular global longitudinal strain (LVGLS); global myocardial work (GMW) indices, which include global work index (GWI), global constructive work (GCW), global wasted work, and global work efficiency; and the LS of subendocardial, middle, and subepicardial layer myocardium during left ventricular systole were measured: left atrial strain of reservoir phase (LASr), left atrial strain of conduit phase (LAScd), and left atrial strain of contraction phase (LASct). One-way ANOVA showed that GLS, GWI, GCW, LASr, and LAScd were closely associated with CTRCD and multivariate logistic regression analysis showed that GLS was the most sensitive predictor for detecting patients at lofty risk of anthracycline-related cardiotoxicity. Both before and after chemotherapy, GLS in the left ventricle showed a pattern of basal segment < middle segment < apical segment and subepicardial < middle < subendocardial layer (p < 0.05), and the degree of decrease also showed a regular pattern of epicardial layer < middle layer < subendocardial layer while the difference was not significant (p > 0.05). After chemotherapy, maximum flow rate in early mitral relaxation/left atrial systolic maximum flow rate (E/A) and left atrial volume index of each group were in the normal range, and the values of LASr, LAScd, and LASct slightly increased in the second cycle and decreased significantly in the fourth cycle after chemotherapy, reaching the lowest level; LASr and LAScd were positively correlated with GLS. LVGLS is a more sensitive and earlier indicator to predict CTRCD compared with conventional echocardiography-related parameters and serological markers, and GLS of each myocardial layer showed a certain regularity. Left atrial strain can be used for early monitoring of cardiotoxicity in children with lymphoma after chemotherapy.

Thallium exposure interfered with heart development in embryonic zebrafish (Danio rerio): From phenotype to genotype

Thallium (Tl) is a rare trace metal element but increasingly detected in wastewater produced by coal-burning, smelting, and more recently, high-tech manufacturing industries. However, the adverse effects of Tl, especially cardiotoxicity, on aquatic biota remain unclear. In this study, zebrafish model was used to elucidate the effects and mechanisms of Tl(I) cardiotoxicity in developing embryos. Exposure of embryonic zebrafish to low-dose Tl(I) (25–100 μg/L) decreased heart rate and blood flow activity, and subsequently impaired swim bladder inflation and locomotive behavior of larvae. Following high-level Tl(I) administration (200–800 μg/L), embryonic zebrafish exhibited pericardial edema, incorrect heart looping, and thinner myocardial layer. Based on RNA-sequencing, Tl(I) altered pathways responsible for protein folding and transmembrane transport, as well as negative regulation of heart rate and cardiac jelly development. The gene expression of nppa, nppb, ucp1, and ucp3, biomarkers of cardiac damage, were significantly upregulated by Tl(I). Our findings demonstrate that Tl(I) at environmentally relevant concentrations interfered with cardiac development with respect to anatomy, function, and transcriptomic alterations. The cardiotoxic mechanisms of Tl(I) provide valuable information in the assessment of Tl-related ecological risk in freshwater environment.

Impact of Rheumatic Process in Left and Right Ventricular Function in Patients with Mitral Regurgitation.

Mitral regurgitation (MR) burdens the left and right ventricles with a volume or pressure overload that leads to a series of compensatory adaptations that eventually lead to ventricular dysfunction, and it is well known that in rheumatic heart disease (RHD) that the inflammatory process not only occurs in the valve but also involves the myocardial and pericardial layers. However, whether the inflammatory process in rheumatic MR is associated with ventricular function besides hemodynamic changes is not yet established. Evaluate whether rheumatic etiology is associated with ventricular dysfunction in patients with chronic MR. The study population comprised patients aged 18 years or older included in the registry who had echocardiography performed at the National Cardiovascular Center Harapan Kita in Indonesia during the study period with isolated primary MR due to rheumatic etiology and degenerative process with at least moderate regurgitation. The current study included 1,130 patients with significant isolated degenerative MR and 276 patients with rheumatic MR. Patients with rheumatic MR were younger and had a higher prevalence of atrial fibrillation and pulmonary hypertension, worse left ventricle (LV) ejection fraction and tricuspid annular plane systolic excursion (TAPSE) value, and larger left atrium (LA) dimension compared to patients with degenerative mitral regurgitation (MR). Gender, age, LV end-systolic diameter, rheumatic etiology, and TAPSE were independently associated with more impaired LV ejection fraction. Whereas low LV ejection fraction, LV end-systolic diameter, and tricuspid peak velocity (TR) peak velocity >3.4 m/s were independently associated with more reduced right ventricle (RV) systolic function (Table 3). Rheumatic etiology was independently associated with more impaired left ventricular function; however, rheumatic etiology was not associated with reduced right ventricular systolic function in a patient with significant chronic MR.

Cardiac magnetic resonance in histologically proven eosinophilic myocarditis

BackgroundEosinophilic myocarditis (EM) is a life-threatening acute heart disease. Cardiac magnetic resonance (CMR) excels in the assessment of myocardial diseases but CMR studies of EM are limited. We aimed to describe CMR findings in histologically proven EM. MethodsPatients with histologically proven EM seen at an academic center from 2000 through 2020 were identified. Of the 28 patients ascertained, 15 had undergone CMR for diagnosis and constitute our study cohort. ResultsThe patients, aged 51 ± 17 years, presented with fever (53%), dyspnea (47%), chest pain (53%), heart block (20%), and blood eosinophilia (60%). On CMR, all 15 patients had myocardial edema with 10 of them (67%) having abnormally high left ventricular (LV) mass as well. LV ejection fraction measured < 50% in 11 patients (73%) and < 30% in 2 (13%), but only 6 (40%) had dilated LV size. Eight patients (53%) had pericardial effusion. LV late gadolinium enhancement (LGE) was found in all but one patient (13/14; 93%). LGE was always multifocal and subendocardial but could involve any myocardial layer. Patients with necrotizing EM by histopathology (n = 6) had higher LGE mass (32.1 ± 16.6% vs 14.5 ± 7.7%, p = 0.050) and more LV segments with LGE (15 ± 2 vs 9 ± 3 out of 17, p = 0.003) than patients (n = 9) without myocyte necrosis. Two patients had LV thrombosis accompanying widespread subendocardial LGE. ConclusionsIn EM, CMR shows myocardial edema and LGE that is typically subendocardial but can involve any myocardial layer. The left ventricle is often non-dilated with moderate-to-severe systolic dysfunction. Pericardial effusion is common. Necrotizing EM presents with extensive myocardial LGE on CMR.

Autonomic nervous system and cardiac neuro-signaling pathway modulation in cardiovascular disorders and Alzheimer's disease.

The heart is a functional syncytium controlled by a delicate and sophisticated balance ensured by the tight coordination of its several cell subpopulations. Accordingly, cardiomyocytes together with the surrounding microenvironment participate in the heart tissue homeostasis. In the right atrium, the sinoatrial nodal cells regulate the cardiac impulse propagation through cardiomyocytes, thus ensuring the maintenance of the electric network in the heart tissue. Notably, the central nervous system (CNS) modulates the cardiac rhythm through the two limbs of the autonomic nervous system (ANS): the parasympathetic and sympathetic compartments. The autonomic nervous system exerts non-voluntary effects on different peripheral organs. The main neuromodulator of the Sympathetic Nervous System (SNS) is norepinephrine, while the principal neurotransmitter of the Parasympathetic Nervous System (PNS) is acetylcholine. Through these two main neurohormones, the ANS can gradually regulate cardiac, vascular, visceral, and glandular functions by turning on one of its two branches (adrenergic and/or cholinergic), which exert opposite effects on targeted organs. Besides these neuromodulators, the cardiac nervous system is ruled by specific neuropeptides (neurotrophic factors) that help to preserve innervation homeostasis through the myocardial layers (from epicardium to endocardium). Interestingly, the dysregulation of this neuro-signaling pathway may expose the cardiac tissue to severe disorders of different etiology and nature. Specifically, a maladaptive remodeling of the cardiac nervous system may culminate in a progressive loss of neurotrophins, thus leading to severe myocardial denervation, as observed in different cardiometabolic and neurodegenerative diseases (myocardial infarction, heart failure, Alzheimer's disease). This review analyzes the current knowledge on the pathophysiological processes involved in cardiac nervous system impairment from the perspectives of both cardiac disorders and a widely diffused and devastating neurodegenerative disorder, Alzheimer's disease, proposing a relationship between neurodegeneration, loss of neurotrophic factors, and cardiac nervous system impairment. This overview is conducive to a more comprehensive understanding of the process of cardiac neuro-signaling dysfunction, while bringing to light potential therapeutic scenarios to correct or delay the adverse cardiovascular remodeling, thus improving the cardiac prognosis and quality of life in patients with heart or neurodegenerative disorders.

Atrial Endocardial Unipolar Voltage Mapping for Detection of Viable Intramural Myocardium: A Proof-of-Concept Study

Endocardial bipolar voltage amplitude is largely derived from endocardial and subendocardial wall layers. This may result in situations of low bipolar voltage amplitude despite the presence of mid-myocardial including epicardial (ie, intramural-epicardial) viable myocardium. This study examined the utility of endocardial unipolar voltage mapping for detection of viable intramural-epicardial atrial myocardium. In 15 swine, an atrial intercaval ablation line with an intentional gap was created. Animals survived for 6 to 8 weeks before electroanatomical mapping followed by sacrifice. Gaps were determined by the presence of electrical conduction and classified based on the histopathologiclly layer(s) of viable myocardium into the following: (1) transmural, (2) endocardial, and (3) intramural-epicardial. Voltage data from healthy, scar, and gap points were exported into excel. The sensitivity and specificity of bipolar and unipolar voltage amplitude to detect intramural-epicardial gaps were compared using receiver operating characteristic analysis. In 9 of 15 (60%) swine, a focal ablation gap was detected in the intercaval line, while in the remainder 6 of 15 (40%), the line was complete without gaps. Gaps were classified into transmural (n=3), endocardial (n=3), or intramural-epicardial (n=3). Intramural-epicardial gaps were characterized by very low bipolar voltage amplitude that was similar to areas with transmural scar (P=0.91). In comparison, unipolar voltage amplitude in intramural-epicardial gaps was significantly higher compared to transmural scar (P<0.001). Unipolar voltage amplitude had higher sensitivity (93% versus 14%, respectively) and similar specificity (95% versus 98%, respectively) to bipolar voltage for detection of intramural-epicardial gaps. Atrial unipolar voltage mapping may be a useful technique for identifying viable intramural-epicardial myocardium in patients with endocardial scar.

Magnetic resonance diagnostic criteria of non-compaction cardiomyopathy: new diagnostic criteria still needed?

Summary Non-compaction cardiomyopathy (NCC) is a rare pathology, but the exact rates of its prevalence are not known due to the lack of a diagnostic gold standard. The purpose of this article is to analyse the available cardiovascular magnetic resonance (CMR) diagnostic criteria of non-compaction described in the literature and to compare their sensitivity and specificity in the diagnosis of NCC. A search of available literature related to the CMR diagnostic criteria of myocardial non-compaction was conducted in the medical database PubMed in February of 2022. The period of publication of scientific articles covered the years from 1996 to 2022. A total of 7 full-text scientific articles were included in the final literature review. The main diagnostic criteria were used: the maximum non-compact (NCM) to compact myocardial layers (CM) ratio (NCM:CM), the percentage of trabeculated left ventricular (LV) myocardial mass, the percentage of trabeculated LV myocardial volume, the non-compact myocardial mass index of the total LV, and the determination of the total LV and the maximal fractal dimension (FD) of the apex with the use of fractal analysis. The lack of accurate diagnostic criteria results in an overdiagnosis of NCC. The highest sensitivity and specificity are associated with the maximum FD &gt; 1.30 of the apex established by applying the fractal analysis method. Fractal analysis requires dedicated software, and this method is difficult to apply in routine clinical practice. Thus, the diagnostic criteria for the NCC using magnetic resonance imaging with higher diagnostic value remain to be sought.

ECHO provides layer-specific insight of both myocardial deformation and microcirculation dysfunction in dilated cardiomyopathy patients: Clinical value of combined application of left ventricular layer-specific strain and myocardial contrast echocardiography.

To investigate the pattern of left ventricular (LV) function and myocardial perfusion and their relationship in dilated cardiomyopathy (DCM) patients using layer-specific speckle tracking imaging (STI) and layer-specific myocardial contrast echocardiography (MCE). Thirty DCM patients and 30 controls were recruited and underwent STI and MCE examination. The peak values of longitudinal strain (LS), circumferential strain (CS) of each layer of LV were recorded and compared between groups. Additionally, cross-sectional area of a microvessel (A) and average myocardial microvascular lesion (β) of each layer were measured, myocardial blood flow (MBF) was estimated using A × β, above parameters were compared between two groups. The LS of endo- (LSendo ), mid- (LSmid ) and epicardium (LSepi ), as well as CS of endo- (RSendo ), mid- (RSmid ), (LSepi ) epicardium and LS endo/epi, CS endo/epi were significantly decreased in DCM patients. More importantly, DCM patients demonstrated decreased A, β and A × β in all three myocardium layers and A endo/epi, β endo/epi, A × β endo/epi compared to the controls. The time to peak and the cardiac cycle required to reach the peak were prolonged in DCM patients (p < 0.05). Longitudinal strain parameters of each layer had a negative relationship with perfusion parameter A and this relationship was strongest between LSendo and Aendo (r=0.690, p < 0.01). The cardiac strain and, more importantly, coronary microcirculation perfusion was impaired in each layer in DCM patients. The longitudinal function of the LV myocardium was closely related to changes in myocardial microcirculation perfusion.

1011 HETEROGENEOUS ARRHYTHMIC PHENOTYPE IN A CASE OF LEFT VENTRICULAR NON COMPACTION CARDIOMYOPATHY

Abstract A young 47 years old female patient was hospitalized in our department for recurrent traumatic syncopal episodes in order to undergo Head Up Tilt Test and Electrophysiology Study (EPS). Her ECG was normal and also transthoracic echocardiography didn't show pathological findings. 24 hour Holter ECG recording showed a short run of polymorphic ventricular tachycardia. Regarding familiar history her mother had died at a young age of sudden death. Head-up tilt test resulted negative for induced-syncope. During hospitalization the patient complained onset of malaise rapidly exiting in syncope: telemetry showed two pauses of 3.8 and 5.1 sec respectively, due to paroxysmal III degree atrio-ventricular block. The day after, the patient underwent electrophysiological study. During programmed ventricular stimulation from RV apex with train and V extrastimolous S1 300 S2 220 induction of syncopal ventricular fibrillation was observed, promptly treated with external DC shock. Cardiac MRI was performed showing diagnostic signs of Left Ventricular non-Compaction Cardiomyopathy. Considering the history of traumatic syncope the patient underwent dual chamber ICD implantation and was discharged. No clinical events in a 6 month follow-up. Genetical analysis was performed and we are waiting for the results. The term left ventricular non-compaction (LVNC) identifies a cardiomyopathy, characterized by intrauterine arrest of the compaction process of the ventricular myocardium during the end of the fourth week, thus leading to the development of prominent trabeculae of the left ventricle, deep intertrabecular recesses and a ventricular wall divider into two different layers of myocardium, the first compact, the other not. This nosological entity is difficult to classify (the European Society of Cardiology considers it as not classifiable among other cardiomyopathies, unlike the American Heart Association) mostly from the point of view of clinical implications, often unpredictable. In fact, we may have completely asymptomatic forms, which, according to some authors, should be considered as normal and completely benign variants, and various manifestations, in which the lack of compaction represents a morphological trait shared by phenotypically distinct forms of cardiomyopathy, such as hypertrophic, dilated and restrictive. LVNC carries an increased risk of ventricular dysfunction resulting in chronic heart failure, thromboembolic events and especially arrhythmic, often ventricular and life-threatening manifestations. A large spectrum of arrhythmias has been observed in patients with non-compact ventricles: in particular, supraventricular and ventricular tachycardias, Wolff-Parkinson-White (WPW) syndrome, but also bradyarrhythmias, which include sinus bradycardia, Sick Sinus Syndrome and various degrees of atrioventricular block, up to complete block. Ventricular tachycardias, including those that progress to ventricular fibrillation, occur in 38–47% of adult patients with LVNC, hence sudden death is often the cause of clinical presentation. Seen the features of the pathology, early diagnosis and family clinical evaluation are necessary aspects in patient management.