Cardiac involvement in eosinophilic granulomatosis with polyangiitis: acute eosinophilic myocarditis and chronic inflammatory cardiomyopathy.

OBJECTIVES: Currently, cardiac involvement is used to describe all eosinophilic granulomatosis with polyangiitis (EGPA) cardiac problems. However, heterogeneity exists among them. We aimed to depict the disease spectrum of EGPA cardiac involvement and identify high-risk population. METHODS: We included EGPA patients hospitalized in our center from 2012 to 2023 and in public databases. Based on the cardiac enzymes, cardiac magnetic resonance imaging, and endomyocardial biopsy results, the patients were divided into 3 groups: eosinophilic myocarditis (EGPA-EM), chronic inflammatory cardiomyopathy (EGPA-ICM) and EGPA-Control. Their clinical, laboratory, imaging results and prognoses were collected and compared. RESULTS: A total of 193 EGPA patients were included, 118 with cardiac involvement (74 EGPA-EM, 44 EGPA-ICM) and 75 control. Among EGPA-control, EGPA-ICM and EGPA-EM, eosinophil increased (6.12/8.71/10.42 × 109/l, p< 0.01), ANCA positivity decreased (41.33/31.82/14.86%, p< 0.01), and lung involvement reduced (73.33/72.73/43.24%, p= 0.02). In EGPA-EM, cardiac troponin further elevated (0.27 vs 6.00 ng/ml, p< 0.01), ejection fractions decreased (57.79 vs 33.20%, p< 0.01), while more ST-T abnormality was observed (41.89 vs 20.45%, p= 0.02). The prognosis of EGPA-EM was significantly worse, with 14.86% death rate, and 2-year event-free survival rate below 50%. Further, we proposed a LATE-EAST diagnostic score (7 items, 9 points) to discriminate EGPA-EM from EGPA-ICM using 4 points as threshold [AUC 0.85 (95%CI 0.78-0.92), sensitivity 0.78, specificity 0.86]. CONCLUSIONS: We first proposed different subtypes of cardiac involvement in EGPA. Identification and treatment of EGPA-EM needs improvement. LATE-EAST score could recognize the high-risk EGPA-EM effectively. Multi-disciplinary treatment is warranted, immunosuppressive therapy should be given timely and anti-IL-5 antibodies be tested in trials.

A fetal rat model of ventricular noncompaction caused by intrauterine hyperglycemia.

BACKGROUND: This study aims to develop a fetal rat model of ventricular noncompaction (NVM) using streptozotocin (STZ)-induced gestational hyperglycemia and compare it with a retinoic acid (RA) model. METHODS: Female SD rats were categorized into STZ, RA, and normal control (NC) groups. The STZ group was given a high-fat diet pre-pregnancy and 35 mg/kg of 2% STZ postpregnancy. The RA group received a 90 mg/kg dose of RA on day 13 postpregnancy. Embryonic myocardial morphology was analyzed through HE staining, and embryonic cardiomyocyte ultrastructures were studied using electron microscopy. Diagnoses of NVM were based on a ratio of noncompact myocardium (N) to compact myocardium (C) >1.4, accompanied by thick myocardial trabeculae and a thin myocardial compaction layer. Kruskal-Wallis test determined N/C ratio differences among groups. RESULTS: Both STZ and RA groups displayed significant NVM characteristics. The left ventricular (LV) N/C in the STZ, RA, and NC groups were 1.983 (1.423-3.527), 1.640 (1.197-2.895), and 0.927 (0.806-1.087), respectively, with a statistically significant difference (P<0.001). The right ventricular (RV) N/C in the STZ, RA, and NC groups were 2.097 (1.364-3.081), 1.897 (1.337-2.662), and 0.869 (0.732-1.022), respectively, with a significant difference (P<0.001). Electron microscopy highlighted marked endoplasmic reticulum swelling in embryonic cardiomyocytes from both STZ and RA groups. CONCLUSION: Our model underscores the pivotal role of an adverse intrauterine developmental environment in the onset of NVM. This insight holds significant implications for future studies exploring the pathogenesis of NVM.

Diagnosis, Genetics, and Management of 24 Patients With Cardiac Paragangliomas: Experience From a Single Center.

Context: Paragangliomas located within the pericardium represent a rare yet challenging clinical situation. Objective: The current analysis aimed to describe the clinical characteristics of cardiac paragangliomas, with emphasis on the diagnostic approach, genetic background, and multidisciplinary management. Methods: Twenty-four patients diagnosed with cardiac paraganglioma (PGL) in Peking Union Medical College Hospital, Beijing, China, between 2003 and 2021 were identified. Clinical data was collected from medical record. Genetic screening and succinate dehydrogenase subunit B immunohistochemistry were performed in 22 patients. Results: The median age at diagnosis was 38 years (range 11-51 years), 8 patients (33%) were females, and 4 (17%) had familial history. Hypertension and/or symptoms related to catecholamine secretion were present in 22 (92%) patients. Excess levels of catecholamines and/or metanephrines were detected in 22 (96%) of the 23 patients who have completed biochemical testing. Cardiac PGLs were localized with 131I-metaiodobenzylguanidine scintigraphy in 11/22 (50%), and 99mTc-hydrazinonicotinyl-tyr3-octreotide scintigraphy in 24/24 (100%) patients. Genetic testing identified germline SDHx mutations in 13/22 (59%) patients, while immunohistochemistry revealed succinate dehydrogenase (SDH) deficiency in tumors from 17/22 (77%) patients. All patients were managed by a multidisciplinary team through medical preparation, surgery, and follow-up. Twenty-three patients received surgical treatment and perioperative death occurred in 2 cases. Overall, 21 patients were alive at follow-up (median 7.0 years, range 0.6-18 years). Local recurrence or metastasis developed in 3 patients, all of whom had SDH-deficient tumors. Conclusion: Cardiac PGLs can be diagnosed based on clinical manifestations, biochemical tests, and appropriate imaging studies. Genetic screening, multidisciplinary approach, and long-term follow-up are crucial in the management of this disease.

Safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple doses of aficamten in healthy Chinese participants: a randomized, double-blind, placebo-controlled, phase 1 study.

Objectives: Aficamten is a selective, small-molecule allosteric inhibitor of cardiac sarcomere being developed as a chronic oral treatment for patients with symptomatic obstructive hypertrophic cardiomyopathy. This was the first-in-Chinese study aiming to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of aficamten in healthy adults. Methods: This double-blind, randomized, placebo-controlled, phase 1 study was conducted in 28 healthy male and female Chinese participants after single ascending dose (SAD) and multi-dose (MD) administrations of aficamten. In the SAD cohort, 16 participants were randomized to receive a single oral dose of aficamten: 10 mg, 20 mg, or placebo. In the MD cohort, 12 participants were randomized to receive multiple doses of aficamten: 5 mg or placebo once daily for 14 days. Safety was monitored throughout the study with electrocardiograms, echocardiograms, clinical laboratory tests, and reporting of adverse events (AEs). Pharmacokinetic profiles of aficamten and metabolites, as well as CYP2D6 genetic impact, were evaluated. Results: A total of 35 treatment-emergent AEs were reported by 14 (50%) participants with mild severity. There were no serious AEs or adverse decreases in left ventricular ejection fraction below 50% during the study. Aficamten was dose-proportional over the dose range of 5-20 mg and accumulated in the MD cohort. Conclusion: Aficamten was safe and well-tolerated in the healthy Chinese adult participants. The pharmacokinetics of aficamten in the Chinese population was comparable to those previously found in Western participants. These phase 1 data support the progression of aficamten into future clinical studies in Chinese patients. Clinical Trial registration: https://clinicaltrials.gov, identifier: NCT04783766.

Reduced myocardial work in asymptomatic heavy alcohol use and its correlation with epicardial adipose tissue volume and serum biomarkers.

BACKGROUND: It is unclear whether long-term heavy alcohol use leads to early cardiac function decline. HYPOTHESIS: Long-term heavy alcohol use developed reduced cardiac function in subclinical status by analyzing myocardial work (MW). Epicardial adipose tissue (EAT) volume and serum biomarkers contribute to identify potential factors sensitive in predicting early cardiac function decline. METHODS: We enrolled 31 asymptomatic participants with heavy alcohol use and 33 age and sex-matching nondrinking individuals. Participants underwent echocardiography, MW analysis, EAT volume measurement, serum biochemical examinations, and body composition assessment. We used multivariate linear regression to identify correlation between MW and total cholesterol (TC), EAT volume, and placental growth factor (PlGF). To determine global work efficiency (GWE) below the normal reference value of 96%, we developed receiver operating curves with area under curve (AUC) to compare different combinations of TC, EAT volume, and PlGF. RESULTS: All 64 participants were male. GWE was reduced in the alcohol use group compared with the control group (96, interquartile range [IQR] = [95-97.75] vs. 97, IQR = [97-98], p = .004). TC was positively associated with GWE (ß = .434, 95% confidence interval [CI] = 0.228 to 1.328, p = .008), whereas EAT volume (ß = -.398, 95% CI = -0.000446 to -0.000093, p = .005) and PlGF (ß = -.493, 95% CI = -1.010 to -0.230, p = .004) were inversely associated with GWE. The most significant AUC for reduced GWE was TC + EAT volume (0.851, 95% CI = 0.671 to 1, p = .006). CONCLUSION: Asymptomatic heavy alcohol use has shown early reduced cardiac function which can be associated with altered fat metabolism, suggesting individuals with alcohol use and abnormal fat metabolism need to be alert to heart damage.

Validation of E/e' Using the Index-Beat Method as an Estimate of Left Atrial Pressure in Patients with Atrial Fibrillation.

INTRODUCTION: Echocardiographic assessment of diastolic function during atrial fibrillation (AF) remains challenging due to the irregular cardiac cycle length. We sought to assess whether the index-beat method, the beat following two preceding cardiac cycles of equal duration, could provide a more reliable measurement of E/e' (mitral E wave/diastolic tissue Doppler velocity) than the conventional averaging of consecutive beats and hence facilitate the noninvasive estimation of elevated left atrial pressure (LAP) in patients with AF. METHODS: We prospectively studied 35 patients with persistent AF who had preserved left ventricular ejection fraction and underwent radiofrequency ablation. LAP was measured in conjunction with transseptal puncture during catheter ablation. Echocardiography was performed 24 h before ablation and E/e' was determined using the recommended averaging of 10 beats and the index-beat method, with the observers blinded to the clinical details and LAP measurements. RESULTS: Correlation analysis showed a strong positive correlation between two methods in terms of both septal E/e' (r = 0.841, p < 0.001) and lateral E/e' (r = 0.930, p < 0.001). Bland-Altman analysis also showed a good agreement between the two measurement methods in terms of E/e'. E/e' determined using both conventional averaging and the index-beat method was significantly correlated with LAP (p < 0.05). After Fisher Z transformation, we found that the index-beat septal E/e' had a better correlation with LAP than did the conventional averaging E/e' (r = 0.736 vs. r = 0.392, Zr = -2.110, p = 0.035). Furthermore, the index-beat method took significantly less time to measure E/e' (mean 33.6 s; 95% confidence intervals [CIs]: 32.1 s-36.2 s) than did conventional averaging method (mean 96.2 s; 95% CI: 90.2 s-102.3 s; p < 0.001). Receiver operating characteristic curve analysis revealed that the optimal cut-off for predicting mean LAP >12 mm Hg was 11 (sensitivity 100%; specificity 77.3%) for index-beat septal E/e' and 16 (sensitivity 61.5%; specificity 95.5%) for index-beat lateral E/e'. CONCLUSIONS: Good correlations were found between E/e' and LAP in patients with AF, particularly with the index-beat method. Moreover, the index-beat method can easily measure E/e' at an accuracy similar to that for the conventional averaging of consecutive beats, which can therefore be applied to assess the diastolic dysfunction and potentially improve the diagnosis of heart failure in patients with AF.

Molecular imaging of fibroblast activation in multiple non-ischemic cardiomyopathies.

BACKGROUND: This pilot study is aimed to perform a pilot visualization study to investigate in vivo fibroblast activation in non-ischemic cardiomyopathies by 68Ga-FAPI-04 PET/CT. METHODS: Twenty-nine consecutive patients with symptomatic non-ischemic cardiomyopathies who underwent 68Ga-FAPI-04 PET/CT were prospectively recruited. Clinical characteristics and echocardiographic parameters were recorded. Cardiac uptake was quantified by standardized uptake values (SUVmax, SUVmean, SUVR) and left ventricular metabolism volume. The relationship between 68Ga-FAPI-04 uptake with clinical and echocardiography parameters was investigated. RESULTS: Heterogeneous 68Ga-FAPI-04 uptake was observed in different subtypes of non-ischemic cardiomyopathies. Twenty-two (75.9%) patients showed elevated 68Ga-FAPI-04 uptake in the left ventricle, and 10 (34.5%) patients also showed slightly diffuse elevated uptake in the right ventricle. Cardiac uptake values were significantly correlated with enlarged ventricular volume evaluated by echocardiography. CONCLUSION: FAPI PET/CT presents a potential value for in vivo visualization and quantification of fibroblast activation on the molecular level. Further study is warranted for investigating the theranostic and prognostic value of elevated FAP signal.

Relationship between left ventricular diastolic function and the risk of left atrial appendage thrombus in patients with nonvalvular atrial fibrillation.

In patients with nonvalvular atrial fibrillation (NVAF), the impact of left ventricular diastolic function on the risk of left atrial appendage (LAA) thrombus has rarely been studied. This prospective study aimed to investigate the relationship between diastolic function and the risk of LAA thrombus in patients with NVAF. Seventy-six patients with NVAF admitted to receive radiofrequency catheter ablation were prospectively enrolled. All the patients underwent transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) in 24 h before ablation. Diastolic function was estimated by TTE including left atrial volume index (LAVI) and E/e', as well as invasive left atrial pressure (LAP) measured during the ablation procedure. LAA peak emptying velocity (LAA-PEV) and the intensity of spontaneous echo contrast (SEC) were determined by TEE. Average E/e', LAVI and mean LAP had a significant positive correlation with the intensity of SEC, the coefficient of correlation were 0.344 (p = 0.002), 0.416 (p < 0.001) and 0.402 (p < 0.001), respectively. After adjustment for CHA2DS2-VASc score and type of AF, multivariate regression analysis revealed that increased LAP (OR 1.144, 95% CI 1.012-1.293, p = 0.031) independently correlated with the risk of LAA thrombus (SEC ≥ Grade 2). LAA-PEV showed a significantly inverse relationship with mean LAP in patients with AF (r = - 0.525, p < 0.001), and in the assessment of elevated LAP with TEE, the LAA-PEV cut-off of 0.40 m/s had a sensitivity of 80%, specificity of 81%. Left ventricular diastolic dysfunction may constitute a potential risk for LAA thrombus and stroke. Furthermore, evaluation of LAA emptying with use of TEE is helpful for assessing the LAP status of patients with AF.

Relative basal myocardial weakness: differentiating dermatomyositis and polymyositis with cardiac involvement from viral myocarditis using speckle-tracking echocardiography and quantification of myocardial work.

Background: Both viral infection and autoimmune diseases like dermatomyositis (DM) and polymyositis (PM) can cause myocarditis and inflammatory cardiomyopathy. It is of great importance to identify underlying etiologies and initiate appropriate treatment. This study aimed to describe the pattern of regional longitudinal strain (LS) and myocardial work in PM/DM patients with cardiac involvement and investigate the usefulness of the pattern to differentiate PM/DM from acute viral myocarditis (AVM) in the clinical setting. Methods: A total of 46 PM/DM patients with cardiac involvement, 24 patients with AVM, and 30 healthy control participants (HCs) were included. Regional myocardial work and strain analyses were performed using two-dimensional (2D) echocardiography to calculate relative basal LS and myocardial work parameters and investigate their value for differential diagnosis. Results: PM and DM are characterized by a pattern of basal myocardial weakness with LS (basal, mid, and apical segments: -15.0±4.4, -17.1±4.7, and -21.4±6.5, respectively), myocardial work index (basal, mid, and apical segments: 1,193±432, 1,272±394, and 1,431±451, respectively), and constructive work (basal, mid, and apical segments: 1,512±422, 1,628±413, and 1,912±433, respectively) that show a base-to-apex gradient in which the myocardium at the base is more severely injured that that of the apex. On cardiovascular magnetic resonance, the positive rate of late gadolinium enhancement was also significantly higher in the basal segments (64%) than the mid (44%) and apical (28%) segments (P=0.038). A relative basal LS of 0.43, defined using the equation [average basal LS/(average mid LS + average apical LS)], had an area under curve (AUC) of 0.88 with high sensitivity (88%) and specificity (78%) to differentiate PM/DM from AVM. Using multivariate logistic regression analysis, relative basal injury of myocardium and creatine kinase elevation were strongly correlated with proximal skeletal muscle weakness according to manual muscle testing (P=0.036 and P=0.010, respectively). Conclusions: Similar to the typical proximal muscle weakness of limbs, PM/DM patients also presented with regionally decreased LS and myocardial work of the basal myocardium. A "basal weakness" pattern is easily recognizable and can be used to accurately differentiate PM/DM with cardiac involvement from AVM.

Initiating ivabradine during hospitalization in patients with acute heart failure: A real-world experience in China.

BACKGROUND: Initiating ivabradine in acute heart failure (HF) is still controversial. HYPOTHESIS: Ivabradine might be effective to be added in acute but hemodynamically stable HF. METHODS: A retrospective cohort of hemodynamically stable acute HF patients was enrolled from January 2018 to January 2020 and followed until July 2020. The primary endpoints were all-cause mortality and rehospitalization for HF. Secondary endpoints included heart rate (HR), cardiac function measured by New York Heart Association (NYHA) class, and left ventricular ejection fraction (LVEF) and adverse events, which were compared between patients with or without ivabradine. RESULTS: A total of 126 patients were enrolled (50 males, median age 54 years, 81% with decompensated HF, median follow-up of 9 months). In patients treated with ivabradine, although baseline HRs were higher than the reference group (96 vs. 80 bpm), they were comparable after 3 months; more patients tolerated high doses of ß-blockers (27% vs. 7.9%), improved to NYHA class I function (55.6% vs. 23.8%) and exhibited normal LVEFs (37.8% vs. 14.3%) than the reference group (all p < .05). Ivabradine was associated with a significant reduction of rehospitalization for HF than the reference group (25.4% vs.61.9%), with longer event-free survival times (hazard ratio: 0.45, 95% confidence interval [CI]: 0.25-0.79), and was related with primary endpoints negatively (hazard ratio 0.51, 95% CI: 0.28-0.91) (all p < .05). CONCLUSION: In patients with acute but hemodynamically stable HF, ivabradine may significantly reduce HR, improve cardiac function, and reduce HF rehospitalization.

TNF-α Inhibitors and Other Biologic Agents for the Treatment of Immune Checkpoint Inhibitor-Induced Myocarditis.

With anti-PD-1 antibodies serving as a representative drug, immune checkpoint inhibitors (ICIs) have become the main drugs used to treat many advanced malignant tumors. However, immune-related adverse events (irAEs), which might involve multiple organ disorders, should not be ignored. ICI-induced myocarditis is an uncommon but life-threatening irAE. Glucocorticoids are the first choice of treatment for patients with ICI-induced myocarditis, but high proportions of steroid-refractory and steroid-resistant cases persist. According to present guidelines, tumor necrosis factor alpha (TNF-α) inhibitors are recommended for patients who fail to respond to steroid therapy and suffer from severe cardiac toxicity, although evidence-based studies are lacking. On the other hand, TNF-α inhibitors are contraindicated in patients with moderate-to-severe heart failure. This review summarizes real-world data from TNF-α inhibitors and other biologic agents for ICI-induced myocarditis to provide more evidence of the efficacy and safety of TNF-α inhibitors and other biologic agents.

Prognostic Value of Left Atrial Strain in Heart Failure: A Systematic Review and Meta-Analysis.

Background: Heart failure (HF) is a global health problem with high morbidity and mortality. Recently, the association between peak atrial longitudinal strain (PALS) and clinical outcomes of HF has gained increasing attention. Our aim was to systematically assess the prognostic value of PALS for adverse events in HF. Methods: PubMed, Embase, and Scopus databases were systematically searched from inception to 30 April 2022. Studies in which PALS was assessed to predict adverse outcomes in adult patients with HF were included. Study selection, quality assessment, and data extraction were performed independently by two authors. The primary endpoints were all-cause death and cardiac hospitalization. Results: Among 7,787 patients in 17 included studies, 3,029 (38.9%) experienced the primary endpoint. Patients with events had lower PALS than those without events [weighted mean difference (WMD) 6.17, 95% confidence interval (CI) 3.09-9.26, p < 0.001]. Each unit increment of PALS was independently associated with decreased risk for the primary endpoint [hazard ratio (HR) 0.96, 95% CI 0.94-0.98, p < 0.001]. The addition of PALS significantly improved the predictive power of conventional risk models [net reclassification index (NRI) 0.22, 95% CI 0.06-0.39, p = 0.008]. Conclusion: Peak atrial longitudinal strain was an independent predictor for all-cause mortality and cardiac hospitalization in patients with HF, highlighting the clinical importance of left atrial (LA) deformation in the prognosis of HF. Systematic Review Registration: [www.crd.york.ac.uk/prospero/], identifier [CRD42020185034].

Prognostic value of left atrial mechanics in cardiac light-chain amyloidosis with preserved ejection fraction: a cohort study.

BACKGROUND: Light-chain amyloidosis is a plasma cell disorder associated with poor outcomes, especially when the heart is involved. The characteristics of left atrial (LA) function and its prognostic implications in cardiac amyloidosis (CA) have not been fully investigated. METHODS: Between April 2014 and June 2019, 93 patients with a diagnosis of CA, normal left ventricular ejection fraction (LVEF) and sinus rhythm were included. Their clinical, baseline echocardiographic and follow-up data were investigated. LA function, including LA strain and strain rate, was assessed using 2D speckle tracking echocardiography in different LA functional phases. RESULTS: Among all patients, 38 (40.9%) died. Multivariate Cox regression analyses showed that LA mechanics regarding LA reservoir and booster pump functions were independent predictors for overall survival. Traditional echocardiographic parameters for LA structure like LA volume index and LA width were not associated with mortality. Moreover, LA strain and strain rate in reservoir and contractile phases improved the discrimination and goodness of fit of the conventional prognostic model, the Mayo criteria 2004 and 2012, in our study population. Decreased LA mechanics were associated with impaired left ventricular (LV) systolic and diastolic function, and LA reservoir and contractile functions were associated with LA structure. CONCLUSIONS: Assessment of LA reservoir and contractile functions via 2D speckle tracking echocardiographic LA mechanical indices provide clinical and prognostic insights into cardiac light-chain amyloidosis patients, especially those with preserved EF and sinus rhythm. Emphasizing the monitoring of LA function may be beneficial for the prognosis prediction of CA.

Predictive Value of Echocardiographic Strain for Myocardial Fibrosis and Adverse Outcomes in Autoimmune Diseases.

Background: Myocardial fibrosis is an important pathophysiologic mechanism of cardiac involvement that leads to increased mortality in patients with autoimmune diseases (AIDs). The aim of this study was to evaluate the association between myocardial strain from speckle-tracking echocardiography (STE) and fibrosis on cardiovascular magnetic resonance (CMR) and to further explore their prognostic implications in patients with AIDs. Methods: We prospectively included 102 AIDs patients with clinically suspected cardiac involvement and 102 age- and sex-matched healthy individuals. Patients underwent CMR for evaluation of myocardial fibrosis by late gadolinium enhancement (LGE) and T1 mapping. A semiquantitative evaluation based on the extent of LGE was used to calculate the total (tLGEs) and segmental (sLGEs) LGE score. Global longitudinal strain (GLS) was evaluated by STE in all subjects. All patients were regularly followed up every 6 months. The primary endpoint was the composite incidence of all-cause death and cardiovascular hospitalization. Results: Compared to healthy controls, AIDs patients had impaired GLS (-17.9 ± 5.1% vs. -21.2 ± 2.5%, p < 0.001). LGE was detected in 70% of patients. Patients with LGE presented worse GLS (-17.1 ± 5.3% vs. -19.6 ± 4.1%, p = 0.018) than those without LGE. On multivariate logistic analysis, GLS ≥ -15% was an independent predictor of LGE presence (OR = 4.98, 95%CI 1.35-18.33, p = 0.016). Moreover, a marked and stepwise impairment of segmental longitudinal strain (-19.3 ± 6.6 vs. -14.9 ± 6.5 vs. -8.9 ± 6.3, p < 0.001) was observed as sLGEs increased. During a median follow-up time of 25 months, 6 patients died, and 14 patients were hospitalized for cardiovascular reasons. Both GLS ≥ -15% (HR 3.56, 95%CI 1.28-9.86, p = 0.015) and tLGEs ≥ 6 (HR 4.13, 95%CI 1.43-11.92, p = 0.009) were independently associated with the primary endpoint. Conclusions: In AIDs patients, impaired myocardial strain on STE could reflect the presence and extent of myocardial fibrosis and provide incremental prognostic value in addition to LGE in the prediction of adverse outcomes.

Electrophysiological, structural, and functional disorders in patients with inflammatory cardiomyopathy secondary to inflammatory myopathy.

BACKGROUND: Inflammatory cardiomyopathy (IC) is a syndrome with chronic myocarditis and cardiac remodeling. This study aimed to explore predicting factors of adverse outcomes in patients with IC secondary to idiopathic inflammatory myopathy (IIM-IC). METHODS: By means of a single-center retrospective study, 52 patients with IIM-IC at Peking Union Medical College Hospital were identified from January 1999 to June 2019. Electrocardiogram and echocardiography data were analyzed for the primary outcome (defined as all-cause death) and secondary outcomes (defined as re-hospitalization of heart failure and all-cause death), using regression and survival analysis. RESULTS: The prevalence of atrial fibrillation, ventricular tachycardia, Q-wave abnormality, left ventricular conduction abnormalities, and reduced left ventricular ejection fraction (LVEF) (≤40%) were 65.4%, 67.3%, 67.3%, 61.6%, and 50.5%. After a median follow-up of 2 years (IQR 0.8-3.0), 26 cases were readmitted due to heart failure. Twenty-two deaths were recorded, including 20 cardiogenic deaths. Among the patients with adverse events, the incidence of poor R-wave progression, low-voltage of the limb leads, Q-wave abnormality, QRS duration >130 ms, left ventricular enlargement, and impaired systolic function were higher. Kaplan-Meier analysis showed that Q-wave abnormality, limb leads low-voltage, LVEF ≤40%, and left ventricular end-diastolic dimension >60 mm were correlated with shorter survival. However, multivariate Cox regression analysis revealed that only Q-wave abnormality (HR = 12.315) and LVEF ≤40% (HR = 5.616) were independent risk factors for all-cause death. CONCLUSION: Q-wave abnormality and reduced LVEF are predictive of poor prognosis in patients with IIM-IC.

IRAK-M deletion aggravates acute inflammatory response and mitochondrial respiratory dysfunction following myocardial infarction: A bioinformatics analysis.

Myocardial infarction (MI) is a major cause of morbidity and mortality worldwide. Interleukin-1 receptor associated kinase (IRAK)-M is a regulator of Toll-like receptor mediated inflammatory responses and plays an important role in the pathophysiologic processes of acute MI. We aimed to explore the effect of IRAK-M on regulating biological function and molecular interactions post-MI through bioinformatics analysis. Datasets from the Gene Expression Omnibus database were used to identify characteristics of IRAK-M expression in MI patients. The expression of IRAK-M was upregulated in MI patients and altered in a time-dependent manner during MI progression. Enrichment analysis showed that biological processes related to inflammatory response and leukocyte activation were markedly activated in MI patients with upregulated IRAK-M. Furthermore, we constructed MI model using wildtype and IRAK-M-/- mice and performed proteomics analysis of infarcted hearts. Functional enrichment of proteomics data indicated that IRAK-M deletion aggravated a series of pathophysiologic functions, such as acute inflammatory response, macrophage activation and mitochondrial dysfunction. S100A8/A9 acted as the central molecule in the above functions based on the protein-protein interaction network and was significantly elevated in IRAK-M-/- infarcted hearts at both the protein and mRNA levels. In conclusion, IRAK-M functioned as an essential regulator in pathophysiologic processes post-MI, exerting effects not only on controlling acute inflammatory responses but also on mediating mitochondrial respiratory function based on integrated bioinformatics analysis. SIGNIFICANCE: In this study, we combined microarray datasets and a proteomics approach to explore the effect of IRAK-M on mediating biological processes and systemic molecular interactions following MI. Our data firstly showed that IRAK-M is involved in ATP synthesis and mitochondrial respiratory chain complex during MI progression. S100A8/A9 acted as the central molecule in above regulatory network and displayed a tight connection with IRAK-M. The findings provide novel evidence and clues for understanding the complex roles and molecular mechanisms of IRAK-M in the development of MI.

Influence of Right Ventricular Dysfunction on Outcomes of Left Ventricular Non-compaction Cardiomyopathy.

BACKGROUND: Various adverse outcomes such as mortality and rehospitalization are associated with left ventricular non-compaction (LVNC). Due to data limitations, prospective risk assessment for LVNC remains challenging. This study aimed to investigate the influence of right ventricular (RV) dysfunction on the clinical outcomes of patients with LVNC through accurate and comprehensive measurements of RV function. METHODS AND RESULTS: Overall, 117 patients with LVNC (47.6 ± 18.3 years, 34.2% male) were enrolled, including 53 (45.3%) and 64 (54.7%) patients with and without RV dysfunction, respectively. RV dysfunction was defined as meeting any two of the following criteria: (i) tricuspid annular systolic excursions <17 mm, (ii) tricuspid S' velocity <10 cm/s, and (iii) RV fractional area change (FAC) <35%. The proportion of biventricular involvement was significantly higher in patients with RV dysfunction than in controls (p = 0.0155). After a follow-up period of 69.0 [33.5, 96.0] months, 18 (15.4%) patients reached the primary endpoint (all-cause mortality), with 14 (26.4%) and 4 (6.3%) from the RV dysfunction group and normal RV function group, respectively. The Kaplan-Meier method and log-rank test revealed that patients with RV dysfunction had a higher risk of all-cause mortality than those in the control group (hazard ratio [HR]: 5.132 [2.003, 13.15], p = 0.0013). Similar results were obtained for patients with left ventricular ejection fraction (LVEF) <50% [HR, 6.582; 95% confidence interval (CI), 2.045-21.19; p = 0.0367]. The relationship between RV dysfunction and heart failure rehospitalization and implantation of implantable cardioverter-defibrillator (ICD)/cardiac resynchronization therapy (CRT) was not statistically significant (both p > 0.05). The multivariable Cox proportional hazard modeling analysis showed that RV dysfunction (HR: 4.950 [1.378, 17.783], p = 0.014) and impaired RV global longitudinal strain (RVGLS) (HR: 1.103 [1.004, 1.212], p = 0.041) were independent predictors of mortality rather than increased RV end-diastolic area and decreased LVEF (both p > 0.05). CONCLUSIONS: RV dysfunction is associated with the prognosis of patients with LVNC.

Characterization of myocardial oxidative metabolism and myocardial external efficiency in high-risk alcohol cardiotoxicity and alcoholic cardiomyopathy via dynamic 11C-Acetate positron emission tomography.

INTRODUCTION: The purpose of this study was to evaluate subjects with high-risk alcohol cardiotoxicity and patients with alcoholic cardiomyopathy (ACM) via dynamic 11C-Acetate positron emission tomography (PET) imaging as a myocardial oxidative metabolic probe. METHODS AND RESULTS: We recruited 37 subjects with chronic alcohol consumption [18 with moderate consumption (MC), 19 with heavy consumption (HC)], 5 ACM patients, and 12 healthy controls to receive dynamic 11C-Acetate PET scans. PET imaging data were analyzed to calculate kinetic parameters (e.g., Kmono, K1 and k2) based on the mono-exponential and one-tissue compartmental models. Myocardial oxygen consumption (MVO2) and myocardial external efficiency (MEE) were then derived from these kinetic parameters. MVO2 was significantly lowered in the HC group and in ACM patients (0.121± 0.018 and 0.111 ± 0.017 mL·g-1·min-1, respectively) compared with those in healthy controls and MC subjects (0.144 ± 0.023 and 0.146 ± 0.027 mL·g-1·min-1, respectively; P < .01). MEE was significantly reduced in ACM patients (13.0% ± 4.3%) compared with those of healthy controls (22.4% ± 4.6%, P < .01), MC subjects (20.1% ± 4.5%, P < .05), and HC subjects (22.3% ± 4.5%, P < .001). CONCLUSION: Functional assessment via dynamic 11C-Acetate PET imaging may represent a clinically feasible probe for identifying cohorts with high-risk cardiotoxicity due to addictive alcohol consumption and ACM.

Interventricular systolic asynchrony predicts prognosis in patients with systemic sclerosis-associated pulmonary arterial hypertension.

OBJECTIVE: Pulmonary arterial hypertension (PAH) is a serious complication of SSc with high mortality. Interventricular systolic asynchrony (IVSA) is observed in PAH patients, but the effect of IVSA and its association with long-term mortality and clinical events in SSc-associated PAH are unclear. This study aimed to investigate the impact of IVSA on the prognosis of SSc-associated PAH. METHODS: Between March 2010 and July 2018, a total of 60 consecutive patients with SSc-associated PAH were enrolled. The end point was a composite of all-cause mortality and clinical worsening. Asynchrony was assessed by colour-coded tissue Doppler imaging (TDI) echocardiography. The myocardial sustained systole curves (Sm) of the basal portion of the right ventricular (RV) free wall and left ventricular (LV) lateral wall were obtained. IVSA was defined as the time difference from the onset of the QRS complex to the end of Sm between LV and RV. RESULTS: Patients with greater IVSA time differences presented with advanced pulmonary vascular resistance (PVR). The IVSA time difference was an independent predictive factor (Hazard Ratio (HR) = 1.018, 95% CI: 1.005, 1.031, P =0.005) for the composite end point and was significantly associated with PVR (r = 0.399, R2=0.092, P =0.002). Kaplan-Meier survival curves showed that patients with greater IVSA had worse prognoses (log-rank P =0.001). CONCLUSION: In conclusion, IVSA analysed by colour-coded TDI echocardiography provided added value as a noninvasive, easy-to-use approach for assessing the prognosis of patients with SSc-associated PAH. A significant IVSA time difference identifies the subgroup of patients at high risk of a poor prognosis.

Empirical anti-tuberculous therapy for the massive pericardial effusion of unknown etiology.

OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of empirical anti-tuberculous therapy (ATT) in patients with massive pericardial effusion (MPE) of unknown etiology in China. METHODS: In-hospital patients with MPE were assessed retrospectively. Based on thorough examination excluding neoplastic, autoimmune, and non-tuberculous infectious diseases, patients who had no evidence of tuberculosis (TB) were treated with empirical ATT (Group A) or not treated with empirical ATT (Group C), whereas those who had evidence of TB were treated with standard ATT (Group B). Clinical outcomes and mitigation of MPE were compared among the three groups to identify the effectiveness of ATT. The survival free of composite endpoint was estimated using the Kaplan-Meier method. RESULTS: A total of 185 eligible patients were recruited: 77 in Group A, 80 in Group B, and 28 in Group C. The average follow-up was 52.9 ± 30.7, 49.4 ± 29.7, and 51.8 ± 30.2 months for Groups A, B, and C, respectively. The incidence of composite endpoint was 23.3, 24.4, and 85.7% in Groups A, B, and C, respectively (p < .0001). However, the clinical recovery rate was greater in Group B compared with Group A (p = .027). No significant difference in the safety profile of ATT was noted between Groups A and B. MPE did not spontaneously decrease in 85.7% of patients in Group C. CONCLUSIONS: Empirical ATT should be considered in MPE of unknown etiology in countries with a high burden of TB.