Myocardial Disease Research Articles

Incorporation of Shared Decision-Making in International Cardiovascular Guidelines, 2012-2022

Shared decision-making (SDM) is a key component of the provision of ethical care, but prior reviews have indicated that clinical practice guidelines seldom promote or facilitate SDM. It is currently unknown whether these findings extend to contemporary cardiovascular guidelines. To identify and characterize integration of SDM in contemporary cardiovascular guideline recommendations using a systematic classification system. This cross-sectional study assessed the latest guidelines or subsequent updates that included pharmacotherapy recommendations and were published between January 2012 and December 2022 by the American College of Cardiology (ACC), Canadian Cardiovascular Society (CCS), and European Society of Cardiology (ESC). Data were analyzed from February 21 to July 21, 2023. All pharmacotherapy recommendations were identified within each guideline. Recommendations that incorporated SDM were rated according to a systematic rating framework to evaluate the quality of SDM incorporation based on directness (range, 1-3; assessing whether SDM was incorporated directly and impartially into the recommendation's text, with 1 indicating direct and impartial incorporation of SDM into the recommendation's text) and facilitation (range, A-D; assessing whether decision aids or quantified benefits and harms were provided, with A indicating that a decision aid quantifying benefits and harms was provided). The proportion of recommendations incorporating SDM was also analyzed according to guideline society and category (eg, general cardiology, heart failure). Analyses included 65 guideline documents, and 33 documents (51%) incorporated SDM either in a general statement or within specific recommendations. Of 7499 recommendations, 2655 (35%) recommendations addressed pharmacotherapy, and of these, 170 (6%) incorporated SDM. By category, general cardiology guidelines contained the highest proportion of pharmacotherapy recommendations incorporating SDM (86 of 865 recommendations [10%]), whereas heart failure and myocardial disease contained the least (9 of 315 recommendations [3%]). The proportion of pharmacotherapy recommendations incorporating SDM was comparable across societies (ACC: 75 of 978 recommendations [8%]; CCS: 29 of 333 recommendations [9%]; ESC: 67 of 1344 recommendations [5%]), with no trend for change over time. Only 5 of 170 SDM recommendations (3%) were classified as grade 1A (impartial recommendations for SDM supported by a decision aid), whereas 114 of 170 recommendations (67%) were grade 3D (SDM mentioned only in supporting text and without any tools or information to facilitate SDM). In this cross-sectional study across guidelines published by 3 major cardiovascular societies over the last decade, 51% of guidelines mentioned the importance of SDM, yet only 6% of recommendations incorporated SDM in any form, and fewer adequately facilitated SDM.

Mechanical Wave Velocities in Left Ventricular Walls in Healthy Subjects and Patients With Aortic Stenosis

BackgroundMechanical wave velocity (MWV) measurement is a promising method for evaluating myocardial stiffness, because these velocities are higher in patients with myocardial disease. ObjectivesUsing high frame rate echocardiography and a novel method for detection of myocardial mechanical waves, this study aimed to estimate the MWVs for different left ventricular walls and events in healthy subjects and patients with aortic stenosis (AS). Feasibility and reproducibility were evaluated. MethodsThis study included 63 healthy subjects and 13 patients with severe AS. All participants underwent echocardiographic examination including 2-dimensional high frame rate recordings using a clinical scanner. Cardiac magnetic resonance was performed in 42 subjects. The authors estimated the MWVs at atrial kick and aortic valve closure in different left ventricular walls using the clutter filter wave imaging method. ResultsMechanical wave imaging in healthy subjects demonstrated the highest feasibility for the atrial kick wave reaching >93% for all 4 examined left ventricular walls. The MWVs were higher for the inferolateral and anterolateral walls (2.2 and 2.6 m/s) compared with inferoseptal and anteroseptal walls (1.3 and 1.6 m/s) (P < 0.05) among healthy subjects. The septal MWVs at aortic valve closure were significantly higher for patients with severe AS than for healthy subjects. ConclusionsMWV estimation during atrial kick is feasible and demonstrates higher velocities in the lateral walls, compared with septal walls. The authors propose indicators for quality assessment of the mechanical wave slope as an aid for achieving consistent measurements. The discrimination between healthy subjects and patients with AS was best for the aortic valve closure mechanical waves. (Ultrasonic Markers for Myocardial Fibrosis and Prognosis in Aortic Stenosis; NCT03422770)

Myocardial extracellular volume fraction is positively associated with activated monocyte subsets among cART-treated persons living with HIV in South Africa

BackgroundDespite treatment with combination antiretroviral therapy (cART), persons living with HIV (PLWH) are at higher risk of cardiac structural abnormalities that may presage clinical heart failure, including myocardial fibrosis. This study assessed whether circulating cellular and soluble protein markers of immune activation cross-sectionally associate with myocardial fibrosis among cART-treated PLWH in South Africa. MethodsParticipants were enrolled in Khayelitsha township near Cape Town, SA. Cardiac magnetic resonance imaging was performed. Plasma protein biomarkers were measured using enzyme-linked immunoassays and monocyte phenotypes were evaluated using flow cytometry. Associations were assessed using multivariable linear and logistic regression. ResultsAmong 69 cART-treated PLWH, mean (SD) age was 48 (10) years, 71% were female, and time since HIV diagnosis was 9 (6) years. Evidence of left ventricular fibrosis by late gadolinium enhancement was present in 74% of participants and mean (SD) extracellular volume fraction (ECV) was 30.9 (5.9)%. Degree of myocardial fibrosis/inflammation measured by ECV was positively associated with percentages of circulating non-classical and intermediate monocyte phenotypes reflecting inflammation and tissue injury. ConclusionThese data generate hypotheses on possible immune mechanisms of HIV-associated non-ischemic myocardial disease, specifically among cART-treated PLWH in sub-Saharan Africa, where the majority of the HIV burden exists globally.

Coronary microvascular dysfunction is a hallmark of all subtypes of MINOCA.

Myocardial infarction without obstructive coronary artery disease (MINOCA) is a heterogeneous clinical condition presenting with myocardial necrosis not due to an obstruction of a major coronary artery. Recently, a relevant role of coronary microvascular dysfunction (CMD) in the pathogenesis of MINOCA has been suggested; however, data on this are scarce. Particularly, it is unclear if CMD is equally present in all subtypes of MINOCA or differentially identifies one or more of these conditions. Therefore, the aim of this study was to assess CMD in all three coronary vessels of MINOCA patients, relating it with the clinical subtype. We retrospectively assessed coronary microvascular function in all three coronary territories by means of angiography-based index of microvascular resistance (aIMR) in 92 patients (64 with working diagnosis ofMINOCA, 28 control patients). To further assess the association of CMD with MINOCA subtypes, MINOCA patients were subdivided according to clinical data in coronary cause (n = 13), takotsubo (n = 13), infiltrative or inflammatory cardiomyopathy (n = 9) or unclear (n = 29). Patients with working diagnosis ofMINOCA showed a significantly elevated average aIMR compared to control patients (30.5 ± 7.6 vs. 22.1 ± 5.9, p < 0.001) as a marker of a relevant CMD; these data were consistent in all vessels. Among MINOCA subtypes, no significant difference in average aIMR could be detected between patients with coronary cause (33.2 ± 6.6), takotsubo cardiomyopathy (29.2 ± 6.9), infiltrative or inflammatory cardiomyopathy (28.1 ± 6.8) or unclear cause (30.6 ± 8.5; p = 0.412). Interestingly, aIMR was significantly elevated in the coronary vessel supplying the diseased myocardium compared with other vessels (31.9 ± 11.4 vs. 27.8 ± 8.2, p = 0.049). Coronary microvascular dysfunction is a hallmark of all MINOCA subtypes. This study adds to the pathophysiological understanding of MINOCA and sheds light into the role of CMD in MINOCA.

Anesthetic Management of Patients with Dilated Cardiomyopathy Undergoing Noncardiac Surgery.

Dilated cardiomyopathy (DCM), a primary myocardial disease, is characterized by dilation of the left or both ventricles and systolic dysfunction with or without congestive heart failure. DCM per se is a well-recognized risk factor for sudden cardiac death and poor surgical outcomes following noncardiac surgery. Surgical trauma/stress represents unique challenges for DCM patient management. Unfortunately, there is a big knowledge gap in managing DCM patients undergoing non-cardiac surgery. Therefore, the aim of our review is to provide basic facts and current advances in DCM, as well as a practical guideline to perioperative care providers, for the management of surgical patients with DCM, who are quite rare compared with the general surgical population. This review summarizes recent advances in the medical management of DCM as well as perioperative assessment and management strategies for DCM patients undergoing noncardiac surgery. Optimal surgical outcomes depend on multiple-disciplinary care to minimize perioperative cardiovascular disturbances.

Emerging Roles of Phospholipase C Beta Isozymes as Potential Biomarkers in Cardiac Disorders.

Phospholipase C (PLC) enzymes represent crucial participants in the plasma membrane of mammalian cells, including the cardiac sarcolemmal (SL) membrane of cardiomyocytes. They are responsible for the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) into 1,2-diacylglycerol (DAG) and inositol (1,4,5) trisphosphate (Ins(1,4,5)P3), both essential lipid mediators. These second messengers regulate the intracellular calcium (Ca2+) concentration, which activates signal transduction cascades involved in the regulation of cardiomyocyte activity. Of note, emerging evidence suggests that changes in cardiomyocytes' phospholipid profiles are associated with an increased occurrence of cardiovascular diseases, but the underlying mechanisms are still poorly understood. This review aims to provide a comprehensive overview of the significant impact of PLC on the cardiovascular system, encompassing both physiological and pathological conditions. Specifically, it focuses on the relevance of PLCβ isoforms as potential cardiac biomarkers, due to their implications for pathological disorders, such as cardiac hypertrophy, diabetic cardiomyopathy, and myocardial ischemia/reperfusion injury. Gaining a deeper understanding of the mechanisms underlying PLCβ activation and regulation is crucial for unraveling the complex signaling networks involved in healthy and diseased myocardium. Ultimately, this knowledge holds significant promise for advancing the development of potential therapeutic strategies that can effectively target and address cardiac disorders by focusing on the PLCβ subfamily.

Exploring Cardiac Effects After Oxytocin 2.5 I U or Carbetocin 100 μg: A Randomised Controlled Trial in Women Undergoing Planned Caesarean Delivery

(Eur J Anaesthesiol. 2022;39:928–938) While oxytocin can be cardioprotective at physiologic levels, higher concentrations are used to prevent postpartum hemorrhage (PPH) and can induce hypotension, ST-depression, tachycardia, arrhythmias, and prolongation of the QTc interval. Further cardiovascular (CV) effects caused directly by oxytocin can result in fatalities in patients with underlying myocardial disease. Such acute risk for susceptible patients warrants characterization of CV changes induced by intravenous oxytocin and its commonly used analog carbetocin as administered to prevent PPH. While carbetocin has demonstrated comparable or improved effect for stimulating uterine contractions and has similar hemodynamic effects to oxytocin, the comparative prevalence of adverse cardiac events is unknown. Myocardial distress can be measured by the release of circulating troponin I (cTnI) and troponin T (cTnT), which are considered indirect indicators of ischemic heart damage. This exploratory Phase 4 randomized trial queried the difference in troponin release following oxytocin or carbetocin administration to approximate the incidence of cardiac adverse events when used to prevent PPH in women undergoing planned cesarean delivery (CD).

Endothelial MICU1 alleviates diabetic cardiomyopathy by attenuating nitrative stress-mediated cardiac microvascular injury

BackgroundMyocardial microvascular injury is the key event in early diabetic heart disease. The injury of myocardial microvascular endothelial cells (CMECs) is the main cause and trigger of myocardial microvascular disease. Mitochondrial calcium homeostasis plays an important role in maintaining the normal function, survival and death of endothelial cells. Considering that mitochondrial calcium uptake 1 (MICU1) is a key molecule in mitochondrial calcium regulation, this study aimed to investigate the role of MICU1 in CMECs and explore its underlying mechanisms.MethodsTo examine the role of endothelial MICU1 in diabetic cardiomyopathy (DCM), we used endothelial-specific MICU1ecKO mice to establish a diabetic mouse model and evaluate the cardiac function. In addition, MICU1 overexpression was conducted by injecting adeno-associated virus 9 carrying MICU1 (AAV9-MICU1). Transcriptome sequencing technology was used to explore underlying molecular mechanisms.ResultsHere, we found that MICU1 expression is decreased in CMECs of diabetic mice. Moreover, we demonstrated that endothelial cell MICU1 knockout exacerbated the levels of cardiac hypertrophy and interstitial myocardial fibrosis and led to a further reduction in left ventricular function in diabetic mice. Notably, we found that AAV9-MICU1 specifically upregulated the expression of MICU1 in CMECs of diabetic mice, which inhibited nitrification stress, inflammatory reaction, and apoptosis of the CMECs, ameliorated myocardial hypertrophy and fibrosis, and promoted cardiac function. Further mechanistic analysis suggested that MICU1 deficiency result in excessive mitochondrial calcium uptake and homeostasis imbalance which caused nitrification stress-induced endothelial damage and inflammation that disrupted myocardial microvascular endothelial barrier function and ultimately promoted DCM progression.ConclusionsOur findings demonstrate that MICU1 expression was downregulated in the CMECs of diabetic mice. Overexpression of endothelial MICU1 reduced nitrification stress induced apoptosis and inflammation by inhibiting mitochondrial calcium uptake, which improved myocardial microvascular function and inhibited DCM progression. Our findings suggest that endothelial MICU1 is a molecular intervention target for the potential treatment of DCM.

PM2.5-Induced Cardiac Structural Modifications and Declined Pro-Survival Signalling Pathways Are Responsible for the Inefficiency of GSK-3β Inhibitor in Attenuating Myocardial Ischemia-Reperfusion Injury in Rats.

Circulatory GSK3β is recognized as a biomarker and therapeutic target for diseases, including myocardial diseases. However, its potential as a target for myocardial ischemia-reperfusion injury (IR) in the presence of PM2.5 exposure is unclear. Wistar rats underwent IR following either a 21-day or single exposure to PM2.5 at a concentration of 250 µg/m3. The effects of GSK3β inhibitor on cardiac physiology, tissue injury, mitochondrial function, and the PI3K/AKT/GSK3β signalling axis were examined. The inhibitor was not effective in improving hemodynamics or reducing IR-induced infarction in the myocardium exposed to PM2.5 for 21 days. However, for a single-day exposure, the inhibitor showed potential in mitigating cardiac injury. In normal hearts undergoing IR, the inhibitor activated the PI3K/AKT signalling pathway, improved mitochondrial function, and reduced oxidative stress. These positive effects were not observed in PM2.5-exposed rats. Furthermore, the inhibitor stimulated autophagy in hearts exposed to PM2.5 for 21 days and subjected to IR, resulting in increased mTOR expression and decreased AMPK expression. In normal hearts and those exposed to a single dose of PM2.5, the inhibitor effectively activated the PI3K/Akt/AMPK axis. These findings suggest that GSK3β may not be a reliable therapeutic target for IR in the presence of chronic PM2.5 exposure.

Predictive utility of stress tests in the detection of asymptomatic coronary artery disease in atherosclerotic stroke patients

IntroductionWhether and how atherosclerotic ischemic stroke patients should be investigated for asymptomatic coronary artery disease (CAD) is controversial. Our aim was to carry out a prospective observational study to determine the frequency and predictors of functionally significant coronary stenosis in these patients as well as the predictors of major adverse cardiovascular events (MACE) during post-stroke follow-up. Material and methodsFrom January 2014 to June 2018, patients with atherosclerotic ischemic stroke were referred from the stroke unit to our cardiovascular department 3+/- 1 months after the acute event where they benefited from evaluation of cardiovascular risk factors, vascular and myocardial disease. Main outcome was defined as the prevalence of myocardial ischemia defined by perfusion stress echography 3 months after stroke. Secondary outcome (MACE) was defined as the incidence of stroke, transient ischemic attack (TIA), acute coronary syndrome, cardiovascular (CV) death or coronary or peripheral revascularization during a 3 year follow-up. ResultsThree hundred and twenty five patients (92% of strokes and 8% TIA) were included and median follow-up was 1075 days. At 3 months post-stroke, myocardial ischemia was found in 17 patients (5.2%). During the 3 year follow-up, 11 MACE occurred (3.4%, all in the non-ischemic group) of which 6 were recurrent strokes. In multivariate analysis, myocardial ischemia was significantly associated with the number of atheromatous vascular beds (OR 4.3; 95% CI, 1.7 to 10.6) and ECG signs of necrosis (OR 6.5; 95% CI, 1.9 to 21.9). MACE were also associated with ECG signs of necrosis (OR 3.5; 95% CI, 1.3 to 9.1), and unrelated to myocardial ischemia. ConclusionMyocardial ischemia and CV events were infrequent and both strongly associated with ECG signs of necrosis, suggesting a low yield of stress tests and the potential for a more straightforward algorithm in the choice of patients eligible to coronary angiogram or other coronary imaging in post-stroke setting.

Abstract P2062: Distinct Stiffness-induced Mechanical Memory Induction And Maintenance In Cardiomyocytes And Cardiac Fibroblasts

Recognizing that cells “feel” and respond to their mechanical environment, recent studies demonstrate that many cells exhibit a phenomenon of “mechanical memory” in which features induced by prior mechanical cues persist after the mechanical stimulus has ceased. While there is a general recognition that different cell types exhibit different responses to changes in extracellular matrix stiffening, the phenomenon of mechanical memory within myocardial cell types has received little attention to date. To probe the dynamics of mechanical memory in cardiomyocytes(CMs) and cardiac fibroblasts (CFs), we developed a magnetorheological elastomer (MRE) cell culture substrate with tunable and reversible stiffness spanning the range from normal to diseased myocardium. Employing IPSC-derived CMs, and CFs while measuring canonical responses to matrix stiffening: cell area, myofibroblasts activation, and chromatin condensation parameter reveals distinct temporal dynamics of mechanical memory induction in each cell type where mechanical memory is invoked much earlier in CMs than in CFs. Experiments using specific inhibitors of cytoskeletal components revealed that induction of mechanical memory is actin-dependent in CFs and microtubule-dependent in CMs. Prevention of α-tubulin detyrosination blocks both induction and maintenance of mechanical memory in CMs. Overall, these results emphasize the distinct temporal dynamics of mechanical memory in CMs and CFs with different cytoskeletal mediators responsible for inducing and maintaining the stiffness activated phenotype. Due to its flexibility, this model is broadly applicable to future studies interrogating mechanotransduction and mechanical memory in the heart and might inform strategies for attenuating the impact of load-dependent pathology and excess myocardial stiffness.

Abstract P2016: Extracellular Stiffness Induces Glucose Dysregulation Via Microtubule-dependent Mechanism

Previous studies have reported profound changes in metabolic fuel utilization pathways during the development of heart failure, including changes in glucose uptake, glucose transporter mislocalization and/or Insulin-resistance. insulin stimulates glucose transport in muscle cells by triggering redistribution of the GLUT4 glucose transporter from an intracellular perinuclear location to the cell surface. Multiple reports have shown that the microtubules in adipocytes and muscle cells play an important role in the insulin-stimulated glucose transport process. We recently demonstrated, using a tunable stiffness substrate mimicking disease myocardium, that we could induces early, cell-autonomous remodeling of adult cardiomyocytes that is dependent on detyrosination of α-tubulin. We therefore employed this culture substrate to define how adult isolated rat cardiomyocytes glucose uptake response is to Insulin when cultured on stiff vs. soft. At the same time, we studied the localization and expression of Glut4 transporter. We found that 48h on stiff substrate was sufficient to induce a loss of insulin sensitivity in our isolated cardiomyocytes. Immunofluorescence reveals a decrease of Glut4 at the Intercalated disc (ID) but show increase of aggregates of the Glut4 transporter at the cell surface. Western Blot analyses shows no change in the total expression of the transporter. Finally, knowing the importance of microtubules network in the trafficking of Glut4, we overexpressed of tubulin tyrosine ligase (TTL) to prevent the detyrosination of microtubules. Surprisingly, TTL not only restored Glut4 at the ID and decreased the number of aggregates, but it also significantly increased glucose uptake as well as the total amount of Glut4 by more than 2-fold compared to soft control. In conclusion, we demonstrated the importance of microtubule dynamics in cardiomyocytes for the Insulin-dependent trafficking of Glut4 to the membrane.

Cardiac mechanics and reverse remodelling under mechanical support from left ventricular assist devices.

In recent years, development of mechanical circulatory support devices has proved to be a new treatment modality, in addition to standard pharmacological therapy, for patients with heart failure or acutely depressed cardiac function. These include left ventricular assist devices, which mechanically unload the heart when implanted. As a result, they profoundly affect the acute cardiac mechanics, which in turn, carry long-term consequences on myocardial function and structural function. Multiple studies have shown that, when implanted, mechanical circulatory assist devices lead to reverse remodelling, a process whereby the diseased myocardium reverts to a healthier-like state. Here, we start by first providing the reader with an overview of cardiac mechanics and important hemodynamic parameters. We then introduce left ventricular assist devices and describe their mode of operation as well as their impact on the hemodynamics. Changes in cardiac mechanics caused by device implantation are then extrapolated in time, and the long-term consequences on myocardial phenotype, as well as the physiological basis for these, is investigated.

Monitoring of Myocardial Involvement in Early Arrhythmogenic Right Ventricular Cardiomyopathy Across the Age Spectrum

BackgroundArrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by fibrofatty replacement of primarily the right ventricular myocardium, a substrate for life-threatening ventricular arrhythmias (VAs). Repeated cardiac imaging of at-risk relatives is important for early disease detection. However, it is not known whether screening should be age-tailored. ObjectivesThe goal of this study was to assess the need for age-tailoring of follow-up protocols in early ARVC by evaluating myocardial disease progression in different age groups. MethodsWe divided patients with early-stage ARVC and genotype-positive relatives without overt structural disease and VA at first evaluation into 3 groups: age <30 years, 30 to 50 years, and ≥50 years. Longitudinal biventricular deformation characteristics were used to monitor disease progression. To link deformation abnormalities to underlying myocardial disease substrates, Digital Twins were created using an imaging-based computational modeling framework. ResultsWe included 313 echocardiographic assessments from 82 subjects (57% female, age 39 ± 17 years, 10% probands) during 6.7 ± 3.3 years of follow-up. Left ventricular global longitudinal strain slightly deteriorated similarly in all age groups (0.1%-point per year [95% CI: 0.05-0.15]). Disease progression in all age groups was more pronounced in the right ventricular lateral wall, expressed by worsening in longitudinal strain (0.6%-point per year [95% CI: 0.46-0.70]) and local differences in myocardial contractility, compliance, and activation delay in the Digital Twin. Six patients experienced VA during follow-up. ConclusionsDisease progression was similar in all age groups, and sustained VA also occurred in patients aged >50 years without overt ARVC phenotype at first evaluation. Unlike recommended by current guidelines, our study suggests that follow-up of ARVC patients and relatives should not stop at older age.

Machine learning for abdominal aortic calcification assessment from bone density machine-derived lateral spine images.

Lateral spine images for vertebral fracture assessment can be easily obtained on modern bone density machines. Abdominal aortic calcification (AAC) can be scored on these images by trained imaging specialists to assess cardiovascular disease risk. However, this process is laborious and requires careful training. Training and testing of model performance of the convolutional neural network (CNN) algorithm for automated AAC-24 scoring utilised 5012 lateral spine images (2 manufacturers, 4 models of bone density machines), with trained imaging specialist AAC scores. Validation occurred in a registry-based cohort study of 8565 older men and women with images captured as part of routine clinical practice for fracture risk assessment. Cox proportional hazards models were used to estimate the association between machine-learning AAC (ML-AAC-24) scores with future incident Major Adverse Cardiovascular Events (MACE) that including death, hospitalised acute myocardial infarction or ischemic cerebrovascular disease ascertained from linked healthcare data. The average intraclass correlation coefficient between imaging specialist and ML-AAC-24 scores for 5012 images was 0.84 (95% CI 0.83, 0.84) with classification accuracy of 80% for established AAC groups. During a mean follow-up 4 years in the registry-based cohort, MACE outcomes were reported in 1177 people (13.7%). With increasing ML-AAC-24 scores there was an increasing proportion of people with MACE (low 7.9%, moderate 14.5%, high 21.2%), as well as individual MACE components (all p-trend <0.001). After multivariable adjustment, moderate and high ML-AAC-24 groups remained significantly associated with MACE (HR 1.54, 95% CI 1.31-1.80 & HR 2.06, 95% CI 1.75-2.42, respectively), compared to those with low ML-AAC-24. The ML-AAC-24 scores had substantial levels of agreement with trained imaging specialists, and was associated with a substantial gradient of risk for cardiovascular events in a real-world setting. This approach could be readily implemented into these clinical settings to improve identification of people at high CVD risk. The study was supported by a National Health and Medical Research Council of Australia Ideas grant and the Rady Innovation Fund, Rady Faculty of Health Sciences, University of Manitoba.

Advancing Precision Medicine in Myocarditis: Current Status and Future Perspectives in Endomyocardial Biopsy-Based Diagnostics and Therapeutic Approaches.

The diagnosis and specific and causal treatment of myocarditis and inflammatory cardiomyopathy remain a major clinical challenge. Despite the rapid development of new imaging techniques, endomyocardial biopsies remain the gold standard for accurate diagnosis of inflammatory myocardial disease. With the introduction and continued development of immunohistochemical inflammation diagnostics in combination with viral nucleic acid testing, myocarditis diagnostics have improved significantly since their introduction. Together with new technologies such as miRNA and gene expression profiling, quantification of specific immune cell markers, and determination of viral activity, diagnostic accuracy and patient prognosis will continue to improve in the future. In this review, we summarize the current knowledge on the pathogenesis and diagnosis of myocarditis and inflammatory cardiomyopathies and highlight future perspectives for more in-depth and specialized biopsy diagnostics and precision, personalized medicine approaches.

Iron Status and Short-Term Recovery after Non-Severe Acute Myocarditis: A Prospective Observational Study.

Pathomechanisms responsible for recovery from acute myocarditis (MCD) or progression to non-ischemic cardiomyopathy have not been comprehensively investigated. Iron, positioned at the crossroads of inflammation and the energy metabolism of cardiomyocytes, may contribute to the pathophysiology of inflammatory myocardial disease. The aim of this study was to evaluate whether systemic iron parameters are related to myocardial dysfunction in MCD patients. We prospectively enrolled 42 consecutive patients hospitalized for MCD. Their iron status and their clinical, laboratory, and echocardiographic indices were assessed during hospitalization and during ambulatory visits six weeks after discharge. A control group comprising healthy volunteers was recruited. The MCD patients had higher serum ferritin and hepcidin and lower serum iron concentration and transferrin saturation (TSAT) than the healthy controls (all p < 0.01). Six weeks after discharge, the iron status of the MCD patients was already comparable to that of the control group. During hospitalization, lower serum iron and TSAT correlated with higher NT-proBNP (both p < 0.05). In-hospital lower serum iron and TSAT correlated with both a lower left ventricular ejection fraction (LVEF) and worse left ventricular global longitudinal strain at follow-up visits (all p < 0.05). In conclusion, in patients with acute MCD, iron status is altered and normalizes within six weeks. Low serum iron and TSAT are related to greater in-hospital neurohormonal activation and subtle persistent left ventricular dysfunction.

Yield of family screening in dilated cardiomyopathy within low-income setting: Tanzanian experience.

Dilated cardiomyopathy (DCM) is often familial and screening of relatives is recommended. However, studies on the yield of screening are scarce in developing countries. The aim of the study was to identify and characterise First-degree relatives of patients with DCM in Tanzania. We recruited first-degree relatives of 57 DCM patients. DCM in the relatives was diagnosed using the 2016 revised definition by the European Society of Cardiology working group on myocardial and pericardial diseases. We screened 120 first-degree relatives. All were asymptomatic (100%) with a median age of 39.0 years (29.5-49.0), slightly over a half (53.3%) were females and 17 (14.1%) were found to have previously unknown DCM. The mean (± SD) indexed left ventricular end-diastolic volume was significantly higher in relatives with DCM (71 ± 11.5 ml) compared to relatives without DCM (50 ± 11.5) (p = 0.001). First-degree relatives of patients with DCM are at risk of developing asymptomatic DCM at a young age.

The Role of Multimodality Imaging in Pediatric Cardiomyopathies.

Cardiomyopathies are a heterogeneous group of myocardial diseases representing the first cause of heart transplantation in children. Diagnosing and classifying the different phenotypes can be challenging, particularly in this age group, where cardiomyopathies are often overlooked until the onset of severe symptoms. Cardiovascular imaging is crucial in the diagnostic pathway, from screening to classification and follow-up assessment. Several imaging modalities have been proven to be helpful in this field, with echocardiography undoubtedly representing the first imaging approach due to its low cost, lack of radiation, and wide availability. However, particularly in this clinical context, echocardiography may not be able to differentiate from cardiomyopathies with similar phenotypes and is often complemented with cardiovascular magnetic resonance. The latter allows a radiation-free differentiation between different phenotypes with unique myocardial tissue characterization, thus identifying the presence and extent of myocardial fibrosis. Nuclear imaging and computed tomography have a complementary role, although they are less used in daily clinical practice due to the concern related to the use of radiation in pediatric patients. However, these modalities may have some advantages in evaluating children with cardiomyopathies. This paper aims to review the strengths and limitations of each imaging modality in evaluating pediatric patients with suspected or known cardiomyopathies.

Significance of electrocardiogram abnormalities in children presenting to the emergency department with acute COVID-19 infection

ObjectivesAcute COVID-19 infection may be associated with electrocardiogram (EKG) abnormalities in pediatric patients. We have anecdotally observed EKG abnormalities in patients without MIS-C or significant cardiac disease requiring intervention or further follow-up. Our aim was to determine the incidence of abnormal EKG findings and correlate with evidence of significant cardiac pathology in pediatric patients who present to the emergency department during an acute COVID-19 infection. MethodsWe conducted a retrospective chart review of 209 pediatric patients diagnosed in the emergency department with acute COVID-19 infection and had an EKG during the same encounter; patients with MIS-C were excluded. Primary objectives included determination of the incidence of EKG abnormalities in patients presenting to the emergency department (ED) with acute COVID-19 infection who did not require hospitalization. Secondary objectives included correlation of these findings with other concomitant testing of possible cardiac pathology (echocardiograms, biomarkers), and clinical outcomes. ResultsEKG abnormalities were identified in 84 (40%) patients. Echo was performed in 28 (13.4%) patients; only 1 was abnormal, and considered an incidental finding. The most common EKG abnormality involved nonspecific ST-T wave patterns, suggestive of but not diagnostic for underlying pericardial or myocardial disease. Serum troponin and BNP values were normal in all patients tested, either with a normal or abnormal EKG. A normal EKG had a 100% sensitivity and negative predictive value in predicting a normal echocardiogram. No patients were hospitalized and there was normalization of EKG abnormalities during short-term follow up. ConclusionsDespite a high incidence of abnormal EKG repolarization patterns in pediatric patients presenting with acute (non-MIS-C) COVID-19 infections, these patients generally do not have abnormal cardiac biomarkers or echocardiograms, and the risk for adverse cardiac events is low.