Primate Model Carrying LMNA Mutation Develops Dilated Cardiomyopathy.

To solve the clinical transformation dilemma of lamin A/C (LMNA)-mutated dilated cardiomyopathy (LMD), we developed an LMNA-mutated primate model based on the similarity between the phenotype of primates and humans. We screened out patients with LMD and compared the clinical data of LMD with TTN-mutated and mutation-free dilated cardiomyopathy to obtain the unique phenotype. After establishment of the LMNA c.357-2A>G primate model, primates were continuously observed for 48 months, and echocardiographic, electrophysiological, histologic, and transcriptional data were recorded. The LMD primate model was found to highly simulate the phenotype of clinical LMD. In addition, the LMD primate model shared a similar natural history with humans.

Heart in Disguise: Unmasking a Novel Gene Deletion in Dilated Cardiomyopathy.

Dilated cardiomyopathy (DCM) is an underrecognized condition with a myriad of etiologies, but it is often labeled idiopathic. However, genetic mutations are emerging as a more common cause of idiopathic DCM than previously believed. Herein, we present a case of a previously healthy 45-year-old woman who presented with three weeks of exertional dyspnea and orthopnea. An echocardiogram showed DCM with severely reduced systolic function and diastolic dysfunction. She was extensively worked up for potential etiologies of her heart failure which included HIV testing, parasite smear, viral serologies, autoimmune testing, cardiac MRI for infiltrative diseases, and coronary catheterization. She was ultimately tested for genetic mutations which revealed a 49-51 exon deletion of the dystrophin (Duchenne muscular dystrophy (DMD)) gene. This case highlights the guideline-based evaluation and management of new-onset heart failure in a healthy 45-year-old female without known predisposing risk factors or family history. It also sheds light on the expansive genetic etiologies that have only recently been identified in those with idiopathic cardiomyopathy. Further research is crucial to improve our understanding of genetic associations of cardiomyopathy.

Histologic characterization of spontaneous catecholamine-induced cardiomyopathy in laboratory New Zealand White rabbits.

Catecholamine-induced cardiomyopathy (CCM) is an entity associated with increased levels of catecholamines causing subendocardial and papillary muscle cardiomyocyte degeneration and necrosis. In 2020, 49 autopsies from early rabbit deaths in a colony used for medical device biocompatibility studies were submitted for microscopic examination. Of the 49 rabbits, 26 had histologic changes consistent with CCM. No common stressor for CCM was determined in affected rabbits. Animals were generally male, were 12-16-wk-old, and were found dead or had bloating, lethargy, and/or diarrhea. Those observed with clinical signs were euthanized and autopsied per the organization's standard operating procedures. Heart lesions consisted of various degrees of apical subendocardial myocardial degeneration and necrosis. Common non-cardiac lesions included pulmonary congestion and edema, hepatic congestion and centrilobular hepatocellular degeneration, and/or variable intestinal submucosal edema.

Biventricular Impairment and Ventricular Interdependence in Patients With Alcoholic Cardiomyopathy: Insights Through Cardiac Magnetic Resonance Imaging.

BACKGROUND: Alcoholic cardiomyopathy (ACM) can lead to progressive cardiac dysfunction and heart failure, but little is known about biventricular impairment and ventricular interdependence (VI) in ACM patients. PURPOSE: To use cardiac MRI to investigate biventricular impairment and VI in ACM patients. STUDY TYPE: Retrospective. POPULATION: Forty-one male patients with ACM and 45 sex- and age-matched controls. FIELD STRENGTH/SEQUENCE: 3.0 T/balanced steady-state free precession sequence, inversion recovery prepared echo-planar imaging sequence and phase-sensitive inversion recovery sequence. ASSESSMENT: Biventricular structure, function, and global strain (encompassing peak strain [PS], peak systolic, and diastolic strain rate), PS of interventricular septal (IVS), microvascular perfusion (including upslope and time to maximum signal intensity [TTM]), late gadolinium enhancement (LGE), and baseline characteristics were compared between the controls and ACM patients. STATISTICAL TESTS: Student's t-test, Mann-Whitney U test, Pearson's correlation, and multivariable linear regression models with a stepwise selection procedure. A two-tailed P value <0.05 was deemed as statistically significant. RESULTS: Compared to control subjects, ACM patients showed significantly biventricular adverse remodeling, reduced left ventricle (LV) global upslope and prolonged global TTM, and the presence of LGE. ACM patients were characterized by a significant decline in all global strain within the LV, right ventricle (RV), and IVS compared with the controls. RV global PS was significantly associated with LV global PS and IVS PS in radial, circumferential, and longitudinal directions. Multivariable analyses demonstrated the longitudinal PS of IVS was significantly correlated with RV global radial PS (ß = 0.614) and circumferential PS (ß = 0.545). Additionally, RV global longitudinal PS (GLPS) was significantly associated with radial PS of IVS (ß = -0.631) and LV GLPS (ß = 1.096). DATA CONCLUSION: ACM patients exhibited biventricular adverse structural alterations and impaired systolic and diastolic function. This cohort also showed reduced LV microvascular perfusion, the presence of LGE, and unfavorable VI. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

Effect of type 2 diabetes on cardiac arrhythmias in patients with obstructive hypertrophic cardiomyopathy.

AIMS: Type 2 diabetes (T2D), a prevalent cardiovascular disease, is linked with cardiac arrhythmias such as atrial fibrillation (AF) and ventricular arrhythmia. This study evaluated T2D's impact on these arrhythmias in patients with obstructive hypertrophic cardiomyopathy (OHCM). METHODS AND MATERIALS: We retrospectively analyzed the data of 75 patients with OHCM and T2D from two medical centers in China from 2011 to 2020. A propensity score-matched cohort of 150 patients without T2D was also analyzed. RESULTS: Altogether, 225 patients were included. The prevalence of supraventricular tachycardia (SVT), AF, and non-sustained ventricular tachycardia (NSVT) was higher in patients with HCM and T2D than in those without T2D. Multivariate logistic regression showed T2D as an independent risk factor for SVT (odds ratio [OR] = 1.90, 95% confidence interval [CI] = 1.01-3.58, P = 0.04), AF (OR = 2.68, 95% CI = 1.27-5.67, P = 0.01), and NSVT (OR = 2.18, 95% CI = 1.04-4.57, P = 0.04). Further analysis identified fasting glucose and glycosylated hemoglobin levels as independent risk factors for AF and NSVT in patients with T2D. CONCLUSIONS: T2D independently increases the risk of cardiac arrhythmias (SVT, AF, NSVT) in OHCM patients. Furthermore, fasting glucose and glycosylated hemoglobin levels independently heighten AF and NSVT risk in OHCM patients with T2D.

Interatrial shunt therapy in advanced heart failure: Outcomes from the open-label cohort of the RELIEVE-HF trial.

AIMS: Heart failure (HF) outcomes remain poor despite optimal guideline-directed medical therapy (GDMT). We assessed safety, effectiveness, and transthoracic echocardiographic (TTE) outcomes during the 12 months after Ventura shunt implantation in the RELIEVE-HF open-label roll-in cohort. METHODS AND RESULTS: Eligibility required symptomatic HF despite optimal GDMT with ≥1 HF hospitalization in the prior year or elevated natriuretic peptides. The safety endpoint was device-related major adverse cardiovascular or neurological events at 30 days, compared to a prespecified performance goal. Effectiveness evaluations included the Kansas City Cardiomyopathy Questionnaire (KCCQ) at baseline, 1, 3, 6, and 12 months and TTE at baseline and 12 months. Overall, 97 patients were enrolled and implanted at 64 sites. Average age was 70 ± 11 years, 97% were in New York Heart Association class III, and half had left ventricular ejection fraction (LVEF) ≤40%. The safety endpoint was achieved (event rate 0%, p < 0.001). KCCQ overall summary score was improved by 12-16 points at all follow-up timepoints (all p < 0.004), with similar outcomes in patients with reduced and preserved LVEF. At 12 months, left ventricular end-systolic and end-diastolic volumes were reduced (p = 0.020 and p = 0.038, respectively), LVEF improved (p = 0.009), right ventricular end-systolic and end-diastolic areas were reduced (p = 0.001 and p = 0.030, respectively), and right ventricular fractional area change (p < 0.001) and tricuspid annular plane systolic excursion (p < 0.001) improved. CONCLUSION: Interatrial shunting with the Ventura device was safe and resulted in favourable clinical effects in patients with HF, regardless of LVEF. Improvements of left and right ventricular structure and function were consistent with reverse myocardial remodelling. These results would support the potential of this shunt device as a treatment for HF.

Arrhythmias and cardiac MRI associations in patients with established cardiac dystrophinopathy.

AIMS: Some patients with cardiac dystrophinopathy die suddenly. Whether such deaths are preventable by specific antiarrhythmic management or simply indicate heart failure overwhelming medical therapies is uncertain. The aim of this prospective, cohort study was to describe the occurrence and nature of cardiac arrhythmias recorded during prolonged continuous ECG rhythm surveillance in patients with established cardiac dystrophinopathy and relate them to abnormalities on cardiac MRI. METHODS AND RESULTS: A cohort of 10 patients (36.3 years; 3 female) with LVEF<40% due to Duchenne (3) or Becker muscular (4) dystrophy or Duchenne muscular dystrophy-gene carrying effects in females (3) were recruited, had cardiac MRI, ECG signal-averaging and ECG loop-recorder implants. All were on standard of care heart medications and none had prior history of arrhythmias.No deaths or brady arrhythmias occurred during median follow-up 30 months (range 13-35). Self-limiting episodes of asymptomatic tachyarrhythmia (range 1-29) were confirmed in 8 (80%) patients (ventricular only 2; ventricular and atrial 6). Higher ventricular arrhythmia burden correlated with extent of myocardial fibrosis (extracellular volume%, p=0.029; native T1, p=0.49; late gadolinium enhancement, p=0.49), but not with LVEF% (p=1.0) on MRI and atrial arrhythmias with left atrial dilatation. Features of VT episodes suggested various underlying arrhythmia mechanisms. CONCLUSIONS: The overall prevalence of arrhythmias was low. Even in such a small sample size, higher arrhythmia counts occurred in those with larger scar burden and greater ventricular volume, suggesting key roles for myocardial stretch as well as disease progression in arrhythmogenesis. These features overlap with the stage of left ventricular dysfunction when heart failure also becomes overt. The findings of this pilot study should help inform the design of a definitive study of specific antiarrhythmic management in dystrophinopathy. TRIAL REGISTRATION NUMBER: ISRCTN15622536.

Screening for immune-related biomarkers associated with myasthenia gravis and dilated cardiomyopathy based on bioinformatics analysis and machine learning.

Background: We aim to investigate genes associated with myasthenia gravis (MG), specifically those potentially implicated in the pathogenesis of dilated cardiomyopathy (DCM). Additionally, we seek to identify potential biomarkers for diagnosing myasthenia gravis co-occurring with DCM. Methods: We obtained two expression profiling datasets related to DCM and MG from the Gene Expression Omnibus (GEO). Subsequently, we conducted differential gene expression analysis and weighted gene co-expression network analysis (WGCNA) on these datasets. The genes exhibiting differential expression common to both DCM and MG were employed for protein-protein interaction (PPI), Gene Ontology (GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Additionally, machine learning techniques were employed to identify potential biomarkers and develop a diagnostic nomogram for predicting MG-associated DCM. Subsequently, the machine learning results underwent validation using an external dataset. Finally, gene set enrichment analysis (GSEA) and machine algorithm analysis were conducted on pivotal model genes to further elucidate their potential mechanisms in MG-associated DCM. Results: In our analysis of both DCM and MG datasets, we identified 2641 critical module genes and 11 differentially expressed genes shared between the two conditions. Enrichment analysis disclosed that these 11 genes primarily pertain to inflammation and immune regulation. Connectivity map (CMAP) analysis pinpointed SB-216763 as a potential drug for DCM treatment. The results from machine learning indicated the substantial diagnostic value of midline 1 interacting protein1 (MID1IP1) and PI3K-interacting protein 1 (PIK3IP1) in MG-associated DCM. These two hub genes were chosen as candidate biomarkers and employed to formulate a diagnostic nomogram with optimal diagnostic performance through machine learning. Simultaneously, single-gene GSEA results and immune cell infiltration analysis unveiled immune dysregulation in both DCM and MG, with MID1IP1 and PIK3IP1 showing significant associations with invasive immune cells. Conclusion: We have elucidated the inflammatory and immune pathways associated with MG-related DCM and formulated a diagnostic nomogram for DCM utilizing MID1IP1/PIK3IP1. This contribution offers novel insights for prospective diagnostic approaches and therapeutic interventions in the context of MG coexisting with DCM.

Hyperglycemia activates FGFR1 via TLR4/c-Src pathway to induce inflammatory cardiomyopathy in diabetes.

Protein tyrosine kinases (RTKs) modulate a wide range of pathophysiological events in several non-malignant disorders, including diabetic complications. To find new targets driving the development of diabetic cardiomyopathy (DCM), we profiled an RTKs phosphorylation array in diabetic mouse hearts and identified increased phosphorylated fibroblast growth factor receptor 1 (p-FGFR1) levels in cardiomyocytes, indicating that FGFR1 may contribute to the pathogenesis of DCM. Using primary cardiomyocytes and H9C2 cell lines, we discovered that high-concentration glucose (HG) transactivates FGFR1 kinase domain through toll-like receptor 4 (TLR4) and c-Src, independent of FGF ligands. Knocking down the levels of either TLR4 or c-Src prevents HG-activated FGFR1 in cardiomyocytes. RNA-sequencing analysis indicates that the elevated FGFR1 activity induces pro-inflammatory responses via MAPKs-NFκB signaling pathway in HG-challenged cardiomyocytes, which further results in fibrosis and hypertrophy. We then generated cardiomyocyte-specific FGFR1 knockout mice and showed that a lack of FGFR1 in cardiomyocytes prevents diabetes-induced cardiac inflammation and preserves cardiac function in mice. Pharmacological inhibition of FGFR1 by a selective inhibitor, AZD4547, also prevents cardiac inflammation, fibrosis, and dysfunction in both type 1 and type 2 diabetic mice. These studies have identified FGFR1 as a new player in driving DCM and support further testing of FGFR1 inhibitors for possible cardioprotective benefits.

Coordination chemistry suggests that independently observed benefits of metformin and Zn2+ against COVID-19 are not independent.

Independent trials indicate that either oral Zn2+ or metformin can separately improve COVID-19 outcomes by approximately 40%. Coordination chemistry predicts a mechanistic relationship and therapeutic synergy. Zn2+ deficit is a known risk factor for both COVID-19 and non-infectious inflammation. Most dietary Zn2+ is not absorbed. Metformin is a naked ligand that presumably increases intestinal Zn2+ bioavailability and active absorption by cation transporters known to transport metformin. Intracellular Zn2+ provides a natural buffer of many protease reactions; the variable "set point" is determined by Zn2+ regulation or availability. A Zn2+-interactive protease network is suggested here. The two viral cysteine proteases are therapeutic targets against COVID-19. Viral and many host proteases are submaximally inhibited by exchangeable cell Zn2+. Inhibition of cysteine proteases can improve COVID-19 outcomes and non-infectious inflammation. Metformin reportedly enhances the natural moderating effect of Zn2+ on bioassayed proteome degradation. Firstly, the dissociable metformin-Zn2+ complex could be actively transported by intestinal cation transporters; thereby creating artificial pathways of absorption and increased body Zn2+ content. Secondly, metformin Zn2+ coordination can create a non-natural protease inhibitor independent of cell Zn2+ content. Moderation of peptidolytic reactions by either or both mechanisms could slow (a) viral multiplication (b) viral invasion and (c) the pathogenic host inflammatory response. These combined actions could allow development of acquired immunity to clear the infection before life-threatening inflammation. Nirmatrelvir (Paxlovid®) opposes COVID-19 by selective inhibition the viral main protease by a Zn2+-independent mechanism. Pending safety evaluation, predictable synergistic benefits of metformin and Zn2+, and perhaps metformin/Zn2+/Paxlovid® co-administration should be investigated.

Molecular mechanisms of metabolic dysregulation in diabetic cardiomyopathy.

Diabetic cardiomyopathy (DCM), one of the most serious complications of diabetes mellitus, has become recognized as a cardiometabolic disease. In normoxic conditions, the majority of the ATP production (>95%) required for heart beating comes from mitochondrial oxidative phosphorylation of fatty acids (FAs) and glucose, with the remaining portion coming from a variety of sources, including fructose, lactate, ketone bodies (KB) and branched chain amino acids (BCAA). Increased FA intake and decreased utilization of glucose and lactic acid were observed in the diabetic hearts of animal models and diabetic patients. Moreover, the polyol pathway is activated, and fructose metabolism is enhanced. The use of ketones as energy sources in human diabetic hearts also increases significantly. Furthermore, elevated BCAA levels and impaired BCAA metabolism were observed in the hearts of diabetic mice and patients. The shift in energy substrate preference in diabetic hearts results in increased oxygen consumption and impaired oxidative phosphorylation, leading to diabetic cardiomyopathy. However, the precise mechanisms by which impaired myocardial metabolic alterations result in diabetes mellitus cardiac disease are not fully understood. Therefore, this review focuses on the molecular mechanisms involved in alterations of myocardial energy metabolism. It not only adds more molecular targets for the diagnosis and treatment, but also provides an experimental foundation for screening novel therapeutic agents for diabetic cardiomyopathy.

Safety and Efficacy of Metabolic Modulation With Ninerafaxstat in Patients With Nonobstructive Hypertrophic Cardiomyopathy.

BACKGROUND: In nonobstructive hypertrophic cardiomyopathy (nHCM), there are no approved medical therapies. Impaired myocardial energetics is a potential cause of symptoms and exercise limitation. Ninerafaxstat, a novel cardiac mitotrope, enhances cardiac energetics. OBJECTIVES: To evaluate the safety and efficacy of ninerafaxstat in nHCM. METHODS: Patients with HCM and left ventricular (LV) outflow gradient <30 mmHg, ejection fraction ≥50% and peak VO2 <80% predicted, were randomized to ninerafaxstat 200 mg BID or placebo (1:1) for 12 weeks. Primary endpoint was safety and tolerability with efficacy outcomes also assessed as secondary endpoints. RESULTS: A total of 67 patients with nHCM were enrolled at 12 centers (57 yrs ± 11.8; 55% women). Serious adverse events occurred in 11.8% (4/34) in the ninerafaxstat group and 6.1% of patients (2/33) in placebo. From baseline to 12 weeks, ninerafaxstat was associated with significantly better ventilatory efficiency (VE/VCO2 slope) compared to placebo with a least square (LS) mean difference between the groups of -2.1 (95% CI, -3.4, -0.6; p=0.006), with no significant difference in pVO2 (p=0.9). KCCQ-CCS was directionally though not significantly improved with ninerafaxstat vs. placebo (LS mean, 3.2 [95% CI, -2.9, 9.2; p=0.2]), though was statistically significant when analyzed post-hoc in the 35 patients with baseline KCCQ-CSS ≤80 (LS mean, 9.4 [95% CI, 0.2, 18.5; p=0.04]). CONCLUSIONS: In symptomatic nHCM, novel drug therapy targeting myocardial energetics was safe and well tolerated and associated with better exercise performance and health status among those most symptomatically limited. The findings support assessing ninerafaxstat in a Phase 3 study.

Patient With Gender Dysphoria Diagnosed With Multiple Sclerosis Following Takotsubo Cardiomyopathy and Ventricular Arrhythmia: A Case Report and Systematic Literature Review.

A 34-year-old transgender woman presented with ventricular tachycardia and was diagnosed with takotsubo cardiomyopathy. Further evaluation revealed an underlying diagnosis of multiple sclerosis (MS) with brainstem lesions that may have triggered takotsubo cardiomyopathy. In this report, we also systematically reviewed published cases of takotsubo cardiomyopathy and MS and found that basal type takotsubo cardiomyopathy was the most common, and most patients presented with brainstem involvement of MS. An awareness of these associations by physicians, along with multidisciplinary collaboration, may facilitate the early diagnosis and improve the prognosis of these patients.

Innovation in surgical treatment of hypertrophic obstructive cardiomyopathy in children.

Hypertrophic cardiomyopathy is the second most common cardiomyopathy affecting children and adolescents and is the main cause of sudden death of young athletes. The natural prognosis of children with severe hypertrophic obstructive cardiomyopathy is not optimistic, and it is not uncommon for children with hypertrophic obstructive cardiomyopathy who do not respond to medication. Surgical treatment is often the only solution. Conventional surgical methods in the past include classic or modified extended Morrow operation, classic or modified Konno operation, and Ross-Konno operation. In recent years, with the development of minimally invasive surgery, various minimally invasive surgical methods have emerged endlessly. Because the incision of minimally invasive cardiac surgery is significantly smaller than that of traditional surgery, it causes less trauma, recovers quickly after surgery, and has the advantage of no difference in surgical effect compared with traditional median sternotomy. Tally endoscopic transmitral myectomy, RTM, minimally right thoracotomy, and other surgical methods have achieved encouraging results in adults and some older children with hypertrophic obstructive cardiomyopathy. The appearance of transapical beating-heart septectomy has brought the treatment of hypertrophic obstructive cardiomyopathy from the era of cardiopulmonary bypass and cardiac arrest to a new era of minimally invasive beating-heart surgery. In the past, there were few articles about the treatment of children with hypertrophic obstructive cardiomyopathy. This article reviewed the new progress and prognosis of surgical treatment of children with hypertrophic obstructive cardiomyopathy at home and abroad.

Long-term Efficacy and Safety of Elamipretide in Patients with Barth Syndrome: 168-Week Open-label Extension Results of TAZPOWER.

PURPOSE: Evaluate long-term efficacy and safety of elamipretide during the open-label extension (OLE) of the TAZPOWER trial in individuals with Barth syndrome (BTHS) . METHODS: TAZPOWER was a 28-week randomized, double-blind, placebo-controlled trial followed by a 168-week OLE. Patients entering the OLE continued elamipretide 40mg subcutaneous daily. OLE primary endpoints were safety and tolerability; secondary endpoints included change from baseline in the 6-minute walk test (6MWT) and BarTH Syndrome Symptom Assessment (BTHS-SA) Total Fatigue. Muscle strength, physician- and patient-assessed outcomes, echocardiographic parameters, and biomarkers, including cardiolipin (CL) and monolysocardiolipin (MLCL), were assessed. RESULTS: Ten patients entered the OLE; 8 reached the Week 168 visit. Elamipretide was well tolerated, with injection site reactions being the most common adverse events. Significant improvements from OLE baseline on 6MWT occurred at all OLE timepoints (cumulative 96.1 meters of improvement [Week 168, p=0.003]). Mean BTHS-SA Total Fatigue scores were below baseline (improved) at all OLE timepoints. 3-D left ventricular stroke, end-diastolic, and end-systolic volumes improved, showing significant trends for improvement from baseline to Week 168. MLCL/CL values showed improvement, correlating to important clinical outcomes. CONCLUSION: Elamipretide was associated with sustained long-term tolerability and efficacy, with improvements in functional assessments and cardiac function in BTHS.

Therapeutic effect of N, N-Diphenyl-1,4-phenylenediamine and adipose-derived stem cells coadministration on diabetic cardiomyopathy in type 1 diabetes mellitus-rat model.

Type 1 diabetes stem-cell-based treatment approach is among the leading therapeutic strategies for treating cardiac damage owing to the stem cells' regeneration capabilities. Mesenchymal stem cells derived from adipose tissue (AD-MSCs) have shown great potential in treating diabetic cardiomyopathy (DCM). Herein, we explored the antioxidant-supporting role of N, N'-diphenyl-1,4-phenylenediamine (DPPD) in enhancing the MSCs' therapeutic role in alleviating DCM complications in heart tissues of type 1 diabetic rats. Six male albinos Wistar rat groups have been designed into the control group, DPPD (250 mg/kg, i.p.) group, diabetic-untreated group, and three diabetic rat groups treated with either AD-MSCs (1 × 106 cell/rat, i.v.) or DPPD or both. Interestingly, all three treated diabetic groups exhibited a significant decrease in serum glucose, HbA1c, heart dysfunction markers (lactate dehydrogenase and CK-MP) levels, and lipid profile fractions (except for HDL-C), as well as some cardiac oxidative stress (OS) levels (MDA, AGEs, XO, and ROS). On the contrary, serum insulin, C-peptide, and various cardiac antioxidant levels (GSH, GST, CAT, SOD, TAC, and HO-1), beside viable cardiac cells (G0/G1%), were markedly elevated compared with the diabetic untreated group. In support of these findings, the histological assay reflected a marked enhancement in the cardiac tissues of all diabetic-treated groups, with obvious excellency of the AD-MSCs + DPPD diabetic-treated group. Such results strongly suggested the great therapeutic potentiality of either DPPD or AD-MSCs single injection in enhancing the cardiac function of diabetic rats, with a great noted enhancement superiority of DPPD and AD-MSCs coadministration.

Accurate diagnosis of apical hypertrophic cardiomyopathy using explainable advanced ECG analysis.

BACKGROUND AND AIMS: Typical electrocardiogram (ECG) features of apical hypertrophic cardiomyopathy (ApHCM) include tall R waves and deep or giant T-wave inversion in the precordial leads, but these features are not always present. The ECG is used as the gatekeeper to cardiac imaging for diagnosis. We tested whether explainable advanced ECG (A-ECG) could accurately diagnose ApHCM. METHODS: A-ECG analysis was performed on standard resting 12-lead ECGs in patients with ApHCM (n = 75 overt, n = 32 relative [<15mm hypertrophy]), a subgroup of which underwent cardiovascular magnetic resonance, n = 92), and comparator subjects (n = 2449), including healthy volunteers (n = 1672), patients with coronary artery disease (n = 372), left ventricular electrical remodelling (n = 108), ischemic (n = 114) or non-ischemic cardiomyopathy (n = 57), and asymmetrical septal hypertrophy (ASH) HCM (n = 126). RESULTS: Multivariable logistic regression identified four A-ECG measures that together discriminated ApHCM from other diseases with high accuracy (area under the receiver operating characteristics curve (AUC) [bootstrapped 95% confidence interval] 0.982 [0.965-0.993]. Linear discriminant analysis also diagnosed ApHCM with high accuracy (AUC 0.989 [0.986-0.991]). CONCLUSION: Explainable A-ECG has excellent diagnostic accuracy for ApHCM, even when the hypertrophy is relative, with A-ECG analysis providing incremental diagnostic value over imaging alone. The electrical (ECG) and anatomical (wall thickness) disease features do not completely align, suggesting future diagnostic and management strategies may incorporate both features.