ABSTRACT
Despite the presence of various signs of cardiac amyloidosis ("red flags"), the introduction into routine practice of new non-invasive diagnostic methods (Speckle Tracking technology using echocardiography, myocardial scintigraphy with technetium pyrophosphate, genetic testing, screening for free light chains of immunoglobulins to exclude AL-amyloidosis), which have high specificity and sensitivity, transthyretinic (ATTR) cardiomyopathy is still a difficult to diagnose disease, especially in the early stages when treatment is most effective. The article presents a clinical case of ATTR-amyloidosis with predominant heart damage, manifested by severe diastolic heart failure resistant to treatment. The timing, from the moment of the first episode of decompensation of heart failure to death, is 4 months, which confirms the rapid progression of severe biventricular dysfunction of the heart. Despite the presence of cardiac and extracardial "red flags" of ATTR-amyloidosis in the patient, the diagnosis was established at autopsy. The paper analyzes possible errors of early diagnosis at the outpatient and inpatient stages of patient management.
Subject(s)
Disease Progression , Heart Failure , Humans , Heart Failure/etiology , Heart Failure/diagnosis , Male , Fatal Outcome , Echocardiography/methods , Amyloid Neuropathies, Familial/diagnosis , Amyloid Neuropathies, Familial/complications , Amyloid Neuropathies, Familial/physiopathology , Middle Aged , Cardiomyopathies/diagnosis , Cardiomyopathies/etiology , Cardiomyopathies/physiopathologyABSTRACT
ABSTRACT: Sepsis is characterized as a systemic inflammatory response syndrome resulting from infection, leading to the development of multiple organ dysfunction syndrome. Sepsis-induced cardiomyopathy (SICM) is a frequently encountered condition in clinical settings. Mesenchymal stem cells (MSCs) possess inherent immunomodulatory and anti-inflammatory attributes, rendering them a promising therapeutic approach to reestablish the equilibrium between anti-inflammatory and proinflammatory systems in septic patients. Consequently, MSCs are frequently employed in clinical investigations. In this study, the author established a mouse SICM model through cecal ligation and puncture and administered MSCs through the tail vein. Following successful modeling, the myocardial function and histopathological changes were detected by echocardiography, hematoxylin-eosin staining, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, enzyme-linked immunosorbent assay,, and other experiments. As a result, MSCs demonstrated the ability to enhance myocardial function, promote cardiac tissue repair, suppress inflammatory response, reduce levels of myocardial injury markers, and mitigate oxidative stress. In addition, transcriptome and proteome analyses were conducted. Through differential expression analysis, functional enrichment analysis, and multiomics association analysis, it was revealed that the transcriptional factors nuclear receptor subfamily 1 (NR1D2) and target gene lipocalin 2 (LCN2) played key roles in mediating the effects of MSCs on SICM. JASPAR website and ChIP-qPCR experiment were used to predict and confirm the targeting relationship between them. Subsequent cell coculture experiments and a series of experiments confirmed that MSCs attenuated cardiomyocyte injury by downregulating the expression of NR1D2 and its downstream target gene LCN2. In conclusion, MSCs alleviate mice SICM through inhibiting NR1D2/LCN2 pathway.
Subject(s)
Cardiomyopathies , Disease Models, Animal , Lipocalin-2 , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Mice, Inbred C57BL , Sepsis , Signal Transduction , Animals , Sepsis/complications , Sepsis/metabolism , Cardiomyopathies/metabolism , Cardiomyopathies/pathology , Cardiomyopathies/etiology , Cardiomyopathies/physiopathology , Cardiomyopathies/therapy , Mesenchymal Stem Cells/metabolism , Male , Lipocalin-2/metabolism , Lipocalin-2/genetics , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Cells, Cultured , Oxidative Stress , Ventricular Function, Left , Mice , ApoptosisABSTRACT
Cardiac sarcoidosis (CS) is difficult to diagnose and often requires a careful evaluation of numerous diagnostic findings. Typical features at initial presentation are a high-grade atrioventricular (AV) block and ventricular tachycardias that cannot be explained by other common entities, especially in younger patients. CS is frequently misdiagnosed and inappropriately treated, which may have deleterious consequences for the patients. In this review article, we focus on special features of the arrhythmias typical of sarcoidosis and also discuss the underlying substrate and the approach in special situations. Furthermore, we provide recommendations from our daily clinical experience, discuss open questions, and explain the need for research.
Subject(s)
Arrhythmias, Cardiac , Cardiomyopathies , Sarcoidosis , Humans , Sarcoidosis/complications , Sarcoidosis/diagnosis , Cardiomyopathies/diagnosis , Cardiomyopathies/therapy , Cardiomyopathies/complications , Cardiomyopathies/etiology , Arrhythmias, Cardiac/etiology , Arrhythmias, Cardiac/diagnosis , Arrhythmias, Cardiac/therapy , Electrocardiography , Diagnosis, Differential , Evidence-Based MedicineABSTRACT
BACKGROUND: Atrial cardiomyopathy (ACM) is responsible for atrial fibrillation (AF) and thromboembolic events. Diabetes mellitus (DM) is an important risk factor for ACM. However, the potential mechanism between ACM and DM remains elusive. METHODS: Atrial tissue samples were obtained from patients diagnosed with AF or sinus rhythm (SR) to assess alterations in NR4A3 expression, and then two distinct animal models were generated by subjecting Nr4a3-/- mice and WT mice to a high-fat diet (HFD) and Streptozotocin (STZ), while db/db mice were administered AAV9-Nr4a3 or AAV9-ctrl. Subsequently, in vivo and in vitro experiments were conducted to assess the impact of NR4A3 on diabetes-induced atrial remodeling through electrophysiological, biological, and histological analyses. RNA sequencing (RNA-seq) and metabolomics analysis were employed to unravel the downstream mechanisms. FINDINGS: The expression of NR4A3 was significantly decreased in atrial tissues of both AF patients and diabetic mice compared to their respective control groups. NR4A3 deficiency exacerbated atrial hypertrophy and atrial fibrosis, and increased susceptibility to pacing-induced AF. Conversely, overexpression of NR4A3 alleviated atrial structural remodeling and reduced AF induction rate. Mechanistically, we confirmed that NR4A3 improves mitochondrial energy metabolism and reduces oxidative stress injury by preserving the transcriptional expression of Sdha, thereby exerting a protective influence on atrial remodeling induced by diabetes. INTERPRETATION: Our data confirm that NR4A3 plays a protective role in atrial remodeling caused by diabetes, so it may be a new target for treating ACM. FUNDING: This study was supported by the major research program of National Natural Science Foundation of China (NSFC) No: 82370316 (to Q-S. W.), No. 81974041 (to Y-P. W.), and No. 82270447 (to Y-P. W.) and Fundation of Shanghai Hospital Development Center (No. SHDC2022CRD044 to Q-S. W.).
Subject(s)
Diabetes Mellitus, Experimental , Energy Metabolism , Oxidative Stress , Animals , Mice , Humans , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/complications , Male , Mice, Knockout , Receptors, Thyroid Hormone/metabolism , Receptors, Thyroid Hormone/genetics , Heart Atria/metabolism , Heart Atria/pathology , Atrial Fibrillation/metabolism , Atrial Fibrillation/etiology , Atrial Fibrillation/prevention & control , Disease Models, Animal , Mitochondria/metabolism , Diabetic Cardiomyopathies/metabolism , Diabetic Cardiomyopathies/etiology , Diabetic Cardiomyopathies/genetics , Diabetic Cardiomyopathies/pathology , Diabetic Cardiomyopathies/prevention & control , Cardiomyopathies/etiology , Cardiomyopathies/metabolism , Atrial Remodeling , DNA-Binding Proteins , Receptors, SteroidABSTRACT
Background: Myocardial inflammation and apoptosis induced by cirrhosis are among the primary mechanisms of cirrhotic cardiomyopathy. CD73, a common extracellular nucleotidase also known as 5'-nucleotidase, is associated with the progression of inflammation and immunity in multiple organs. However, the mechanism by which CD73 contributes to myocardial inflammation and apoptosis in cirrhosis remains unclear. Methods: In this study, a cirrhotic cardiomyopathy model in mice was established by bile duct ligation. Myocardial-specific overexpression of CD73 was achieved by tail vein injection of AAV9 (adeno-associated virus)-cTNT-NT5E-mCherry, and cardiac function in mice was assessed using echocardiography. Myocardial inflammation infiltration and apoptosis were evaluated through pathological observation and ELISA assays. The expression of CD73, A2AR, apoptotic markers, and proteins related to the NF-κB pathway in myocardial tissue were measured. Results: In the myocardial tissue of the cirrhotic cardiomyopathy mouse model, the expression of CD73 and A2AR increased. Overexpression of CD73 in the myocardium via AAV9 injection and stimulation of A2AR with CGS 21680 inhibited myocardial inflammation and cardiomyocyte apoptosis induced by cirrhosis. Additionally, overexpression of CD73 suppressed the activation of the NF-κB pathway by upregulating the expression of the adenosine receptor A2A. Conclusion: Our study reveals that the CD73/A2AR signaling axis mitigates myocardial inflammation and apoptosis induced by cirrhosis through negative feedback regulation of the NF-κB pathway.
Subject(s)
5'-Nucleotidase , Cardiomyopathies , Liver Cirrhosis , Receptor, Adenosine A2A , Signal Transduction , Animals , Male , Mice , 5'-Nucleotidase/metabolism , Apoptosis , Cardiomyopathies/metabolism , Cardiomyopathies/etiology , Cardiomyopathies/immunology , Disease Models, Animal , Feedback, Physiological , GPI-Linked Proteins , Liver Cirrhosis/immunology , Liver Cirrhosis/metabolism , Mice, Inbred C57BL , NF-kappa B/metabolism , Receptor, Adenosine A2A/metabolismABSTRACT
Objective: To investigate the value of myocardium scar area in predicting adverse cardiovascular events (MACEs) after coronary artery bypass grafting (CABG) in patients with ischemic cardiomyopathy (ICM). Methods: The first part of this study was a retrospective study. Patients diagnosed with ICM and undergoing CABG surgery at Beijing Anzhen Hospital, Capital Medical University from January 2017 to December 2022 were enrolled as the discovery cohort. All patients underwent cardiac magnetic resonance-late gadolinium enhancement (CMR-LGE) before surgery. According to the occurrence of postoperative MACEs, the patients were divided into MACEs group and MACEs-free group. Preoperative clinical and imaging data, intraoperative and postoperative data were collected and compared between the two groups. The primary endpoint was postoperative MACEs. Univariate and multifactor regression analyses were used to analyze the risk factors for MACEs. Receiver operating characteristic (ROC) curves were constructed to evaluate the predictive efficacy and optimal cut-off value of myocardial scar area for endpoint events. The second part of this study was a prospective study. Patients with ICM who received CABG at Beijing Anzhen Hospital, Capital Medical University from January 2023 to June 2023 were enrolled as a validation cohort, and were divided into MACEs group and MACEs-free group according to whether MACEs occurred after surgery. Preoperative clinical and imaging data, intraoperative and postoperative data were collected and compared between the two groups. Verify the reliability of the cut-off value obtained by ROC curve in the validation cohort. Results: A total of 120 patients with ICM (30 patients in MACEs group and 90 patients in MACEs-free group), aged (61.6±8.7) years, including 93 males, were included in the discovery cohort. A total of 22 ICM patients (5 patients in MACEs group and 17 patients in MACEs-free group), aged (59.5±8.2) years, including 18 males, were included in the validation cohort. Multivariate Cox regression showed that myocardial scar area (HR=1.258, 95%CI 1.096-1.444, P=0.001) was an independent risk factor for the primary endpoint event. The area under ROC curve of myocardial scar area for predicting postoperative MACEs was 0.90 (95%CI 0.83-0.95), and myocardial scar area≥36.0% was the optimal cut-off value for predicting postoperative MACEs, and its sensitivity, specificity and accuracy were 96.7%, 72.2% and 78.3%, respectively. In the validation cohort, the sensitivity, specificity and accuracy of myocardial scar area in predicting postoperative MACEs in patients with ICM after CABG were 80.0%, 82.4% and 81.8%, respectively. Conclusion: Myocardial scar area is an independent risk factor for MACEs after CABG in patients with ICM, and myocardial scar area≥36.0% is the optimal cut-off value for predicting MACEs after CABG. Myocardial scar area can help to identify patients at high risk of surgery and provide a basis for risk stratification of patients.
Subject(s)
Cardiomyopathies , Cicatrix , Coronary Artery Bypass , Myocardial Ischemia , Humans , Coronary Artery Bypass/adverse effects , Coronary Artery Bypass/methods , Retrospective Studies , Myocardial Ischemia/etiology , Cicatrix/etiology , Cardiomyopathies/etiology , Risk Factors , Female , Male , Prospective Studies , Postoperative Complications/etiology , ROC Curve , Middle Aged , Myocardium/pathologyABSTRACT
Septic cardiomyopathy (SCM) is a severe complication caused by sepsis, resulting in a high mortality rate. The current understanding of the pathogenic mechanism of SCM primarily involves endocardial injury, microcirculation disturbance, mitochondrial dysfunction and fibrosis. Heparanase (HPA), an endo-ß-D-glucuronidase, has been implicated in inflammation, immune response, coagulation promotion, microcirculation disturbance, mitochondrial dysfunction and fibrosis. Therefore, it was hypothesized that HPA may play an important role in the pathogenesis of SCM. The present study provides a summary of various pathophysiological changes and mechanisms behind the involvement of HPA in SCM. It also presents a novel perspective on the pathogenic mechanism, diagnosis and treatment of SCM.
Subject(s)
Cardiomyopathies , Glucuronidase , Sepsis , Humans , Glucuronidase/blood , Cardiomyopathies/etiology , Sepsis/complicationsABSTRACT
BACKGROUND: The adverse effects of a Western diet on obesity and diabetes among reproductive-aged women pose a significant threat to the cardiovascular health of their offspring. Given the crucial role of glutathione metabolism and glutathione-related antioxidant defense systems in cardiovascular diseases through scavenging ROS and maintaining redox homeostasis, further exploration of their specific influence is imperative to develop therapeutic strategies for cardiomyopathy induced by a maternal Western diet. METHODS: We developed a prenatal maternal Western diet exposure model in C57/B6 mice to investigate cardiac morphology and function through histological analysis and echocardiography. RNA sequencing and analysis were utilized to elucidate the mechanisms underlying the impact of a maternal Western diet and N-acetylcysteine treatment on cardiomyopathy. Additionally, ELISAs, transmission electron microscopy, and flow cytometry were employed to assess the antioxidant defense system and mitochondrial ROS levels in progenitor cardiomyocytes. RESULTS: N-acetylcysteine significantly mitigated cardiomyocyte hypertrophy, myocardial interstitial fibrosis, collagen type I accumulation, and left ventricular remodeling induced by a maternal Western diet, particularly in male offspring. Furthermore, N-acetylcysteine reversed the increase in apoptosis and the increase in the ß/α-MyHC ratio in the myocardium of offspring that results from a maternal Western diet. RNA sequencing and GSEA revealed that the beneficial effects of N-acetylcysteine were linked to its ability to modulate oxidative phosphorylation pathways. Additionally, N-acetylcysteine treatment during pregnancy can markedly elevate glutathione levels, augment glutathione peroxidase (GPx) activity, and mitigate the accumulation of mitochondrial ROS caused by a maternal Western diet. CONCLUSIONS: N-acetylcysteine mitigated cardiomyopathy induced by a maternal Western diet by bolstering glutathione synthesis and enhancing GPx activity, thereby scavenging mitochondrial ROS and modulating oxidative phosphorylation pathways.
Subject(s)
Acetylcysteine , Cardiomyopathies , Diet, Western , Glutathione , Mice, Inbred C57BL , Animals , Female , Glutathione/metabolism , Cardiomyopathies/etiology , Cardiomyopathies/metabolism , Pregnancy , Mice , Acetylcysteine/pharmacology , Diet, Western/adverse effects , Male , Reactive Oxygen Species/metabolism , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/drug effects , Maternal Nutritional Physiological Phenomena , Antioxidants/pharmacology , Disease Models, Animal , Prenatal Exposure Delayed Effects , Myocardium/metabolism , Oxidative Stress/drug effectsABSTRACT
Thyrotoxic periodic paralysis (TPP) and thyrotoxic cardiomyopathy (TCMP) are potentially lethal complications of thyrotoxicosis that require emergent recognition and management to attenuate significant morbidity and mortality. We present the case of a 23-year-old Asian male with no prior medical history who developed TPP with coincident TCMP, which was successfully managed with antithyroid and heart failure therapies. The clinician should be aware of the diagnosis and treatment of these 2 life-threatening conditions in a hyperthyroid state.
Subject(s)
Antithyroid Agents , Cardiomyopathies , Hypokalemic Periodic Paralysis , Thyrotoxicosis , Humans , Male , Hypokalemic Periodic Paralysis/diagnosis , Hypokalemic Periodic Paralysis/etiology , Thyrotoxicosis/complications , Thyrotoxicosis/diagnosis , Young Adult , Cardiomyopathies/etiology , Cardiomyopathies/complications , Cardiomyopathies/diagnosis , Antithyroid Agents/therapeutic use , ElectrocardiographyABSTRACT
BACKGROUND: High levels of catecholamines are cardiotoxic and associated with stress-induced cardiomyopathies. Using a septic shock model that reproduces the reversible cardiomyopathy seen over 10 days associated with human septic shock, we investigated the effects of catecholamines on microcirculatory perfusion and cardiac dysfunction. METHODS AND RESULTS: Purpose-bred beagles received intrabronchial Staphylococcus aureus (n=30) or saline (n=6). The septic animals were than randomized to epinephrine (1 µg/kg per minute, n=15) or saline (n=15) infusions from 4 to 44 hours. Serial cardiac magnetic resonance imaging, catecholamine levels, and troponins were collected over 92 hours. Serial adenosine-stress perfusion cardiac magnetic resonance imaging was performed on septic animals randomized to receive saline (n=8 out of 15) or epinephrine (n=8 out of 15). High-dose sedation was given to suppress endogenous catecholamine release. Despite catecholamine levels largely remaining within the normal range throughout, by 48 hours, septic animals receiving saline versus nonseptic animals still developed significant worsening of left ventricular ejection fraction, circumferential strain, and ventricular-aortic coupling. In septic animals that received epinephrine versus saline infusions, plasma epinephrine levels increased 800-fold, but epinephrine produced no significant further worsening of left ventricular ejection fraction, circumferential strain, or ventricular-aortic coupling. Septic animals receiving saline had a significant increase in microcirculatory reserve without troponin elevations. Septic animals receiving epinephrine had decreased edema, blunted microcirculatory perfusion, and elevated troponin levels that persisted for hours after the epinephrine infusion stopped. CONCLUSIONS: Cardiac dysfunction during sepsis is not primarily due to elevated endogenous or exogenous catecholamines nor due to decreased microvascular perfusion-induced ischemia. However, epinephrine itself has potentially harmful long-lasting ischemic effects during sepsis including impaired cardiac microvascular perfusion that persists after stopping the infusion.
Subject(s)
Cardiomyopathies , Disease Models, Animal , Epinephrine , Microcirculation , Shock, Septic , Animals , Dogs , Shock, Septic/physiopathology , Shock, Septic/complications , Shock, Septic/blood , Epinephrine/blood , Microcirculation/drug effects , Cardiomyopathies/physiopathology , Cardiomyopathies/blood , Cardiomyopathies/etiology , Stroke Volume/drug effects , Coronary Circulation/drug effects , Myocardial Ischemia/physiopathology , Myocardial Ischemia/blood , Myocardial Ischemia/complications , Ventricular Function, Left/drug effects , Catecholamines/blood , Troponin/blood , Staphylococcal Infections/microbiology , Staphylococcal Infections/complications , Staphylococcal Infections/physiopathology , Time Factors , Myocardial Perfusion Imaging/methods , Magnetic Resonance ImagingABSTRACT
OBJECTIVE: To describe the epidemiological, clinical, paraclinical, therapeutic and evolutionary characteristics of of peripartum cardiomyopathy (PPCM) in the internal medicine department of the Zinder National Hospital (ZNH). METHODS: This was a descriptive cross-sectional study carried out from 2018 to 2022 at the ZNH Department of Internal Medicine. Included were all patients admitted for PPCM who met National Heart Blood and Lung Institute criteria. The data collected was analyzed using Excel and EPI INFO v7. RESULTS: We had collected 100 cases of PPCM out of a total of 8706 hospitalized patients, i.e. a hospital prevalence of 1.14%. The mean age of the patients was 27.9 years ± 7.4 [17-45]. The majority of patients were from underprivileged social strata (n=64). The risk factors for PMPC found were essentially hot bath (n=66), home birth (n=40), natron porridge (n=35) and multiparity (n=57). Cardiac symptomatology appeared postpartum in 56% of patients. Dyspnea was the main symptom in 98% of cases. The physical signs were dominated by the functional systolic murmur (66%). Three quarters (75%) of the patients had congestive heart failure. Electrocardiographic signs were dominated by left ventricular hypertrophy (n=65). Cardiomegaly was present in 94% of patients. Left ventricular ejection fraction was altered in all patients. Impaired renal function was found in 31% of patients. Management was based on a low-sodium diet tripod, diuretics and converting enzyme inhibitors. Two cases of death were recorded. CONCLUSION: PPCM is common in the Zinder region. It affects young women with several risk factors and is revealed by signs of congestive heart failure. For a better understanding of this still poorly elucidated condition, it is necessary to pursue research efforts.
Subject(s)
Cardiomyopathies , Peripartum Period , Pregnancy Complications, Cardiovascular , Humans , Female , Adult , Cross-Sectional Studies , Pregnancy , Cardiomyopathies/epidemiology , Cardiomyopathies/diagnosis , Cardiomyopathies/etiology , Young Adult , Pregnancy Complications, Cardiovascular/epidemiology , Pregnancy Complications, Cardiovascular/diagnosis , Middle Aged , Adolescent , Niger/epidemiology , Risk Factors , Prevalence , Puerperal Disorders/epidemiology , Puerperal Disorders/diagnosis , Puerperal Disorders/etiology , Health Resources/statistics & numerical dataSubject(s)
Atrial Fibrillation , Cardiomyopathies , Heart Failure , Humans , Atrial Fibrillation/complications , Atrial Fibrillation/physiopathology , Cardiomyopathies/physiopathology , Cardiomyopathies/etiology , Cardiomyopathies/complications , Heart Failure/etiology , Heart Failure/physiopathology , Male , Female , Aged , Middle Aged , Risk FactorsSubject(s)
Amyloidosis , Aortic Valve Stenosis , Transcatheter Aortic Valve Replacement , Humans , Amyloidosis/surgery , Aortic Valve Stenosis/surgery , Cardiomyopathies/surgery , Cardiomyopathies/etiology , Meta-Analysis as Topic , Transcatheter Aortic Valve Replacement/adverse effects , Treatment OutcomeABSTRACT
Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease caused by mutations to the dystrophin gene, resulting in deficiency of dystrophin protein, loss of myofiber integrity in skeletal and cardiac muscle, and eventual cell death and replacement with fibrotic tissue. Pathologic cardiac manifestations occur in nearly every DMD patient, with the development of cardiomyopathy-the leading cause of death-inevitable by adulthood. As early cardiac abnormalities are difficult to detect, timely diagnosis and appropriate treatment modalities remain a challenge. There is no cure for DMD; treatment is aimed at delaying disease progression and alleviating symptoms. A comprehensive understanding of the pathophysiological mechanisms is crucial to the development of targeted treatments. While established hypotheses of underlying mechanisms include sarcolemmal weakening, upregulation of pro-inflammatory cytokines, and perturbed ion homeostasis, mitochondrial dysfunction is thought to be a potential key contributor. Several experimental compounds targeting the skeletal muscle pathology of DMD are in development, but the effects of such agents on cardiac function remain unclear. The synergistic integration of small molecule- and gene-target-based drugs with metabolic-, immune-, or ion balance-enhancing compounds into a combinatorial therapy offers potential for treating dystrophin deficiency-induced cardiomyopathy, making it crucial to understand the underlying mechanisms driving the disorder.
Subject(s)
Cardiomyopathies , Mitochondria , Muscular Dystrophy, Duchenne , Muscular Dystrophy, Duchenne/complications , Muscular Dystrophy, Duchenne/therapy , Muscular Dystrophy, Duchenne/pathology , Humans , Cardiomyopathies/therapy , Cardiomyopathies/metabolism , Cardiomyopathies/pathology , Cardiomyopathies/etiology , Animals , Mitochondria/metabolism , Dystrophin/metabolism , Dystrophin/genetics , Dystrophin/deficiencyABSTRACT
(1) Heart transplantation (HTX) improves the overall survival and functional status of end-stage heart failure patients with cardiomyopathies (CMPs). The majority of CMPs have genetic causes, and the overlap between CMPs and inherited myopathies is well documented. However, the long-term outcome in skeletal muscle function and possibility of an undiagnosed underlying genetic cause of both a cardiac and skeletal pathology remain unknown. (2) Thirty-nine patients were assessed using open and standardized interviews on muscle function, a quality-of-life (EuroQol EQ-5D-3L) questionnaire, and a physical examination (Medical Research Council Muscle scale). Whole-exome sequencing was completed in three stages for those with skeletal muscle weakness. (3) Seven patients (17.9%) reported new-onset muscle weakness and motor limitations. Objective muscle weakness in the upper and lower extremities was seen in four patients. In three of them, exome sequencing revealed pathogenic/likely pathogenic variants in the genes encoding nexilin, myosin heavy chain, titin, and SPG7. (4) Our findings support a positive long-term outcome of skeletal muscle function in HTX patients. However, 10% of patients showed clinical signs of myopathy due to a possible genetic cause. The integration of genetic testing and standardized neurological assessment of motor function during the peri-HTX period should be considered.
Subject(s)
Heart Transplantation , Neuromuscular Diseases , Humans , Heart Transplantation/adverse effects , Male , Female , Middle Aged , Neuromuscular Diseases/genetics , Adult , Quality of Life , Exome Sequencing , Muscle, Skeletal/pathology , Muscle, Skeletal/physiopathology , Aged , Heart Failure/genetics , Heart Failure/surgery , Heart Failure/etiology , Cardiomyopathies/genetics , Cardiomyopathies/etiology , Muscle Weakness/etiology , Muscle Weakness/genetics , Connectin/geneticsABSTRACT
AIMS: Patients with transthyretin amyloid cardiomyopathy (ATTR-CM) experience reduced functional capacity. We evaluated changes in functional capacity over extensive follow-up using cardiopulmonary exercise testing (CPX). METHODS: ATTR-CM patients underwent CPX and blood testing at baseline, first [V1, 8 (6-10) months] and second follow-up (V2) at 35 (26-41) months after start of disease-specific therapy. RESULTS: We included 34 ATTR-CM patients, aged 77 (±6) years (88.2% men). CPX showed two patterns with functional capacity improvement at V1 and deterioration at V2. Peak work capacity ( P = 0.005) and peak oxygen consumption (VO 2 , P = 0.012) increased at V1 compared with baseline and decreased at V2. The ventilation to carbon dioxide relationship slope (VE/VCO 2 ) increased at V2 compared with baseline and V1 ( P = 0.044). A cut-off for peak VO 2 at 14âml/kg·min showed more events (composite of death and heart failure hospitalization): less than 14 vs. greater than 14âml/kg·min ( P â=â0.013). Cut-offs for VE/VCO 2 slope at 40 showed more events greater than 40 vs. less than 40 ( P â=â0.009). CONCLUSION: ATTR-CM patients showed an improvement and deterioration in the short-term and long-term follow-up, respectively, with a better prognosis for those with peak VO 2 above 14âml/kg·min and for a VE/VCO 2 slope below 40.
Subject(s)
Amyloid Neuropathies, Familial , Cardiomyopathies , Exercise Test , Exercise Tolerance , Oxygen Consumption , Humans , Male , Female , Aged , Amyloid Neuropathies, Familial/diagnosis , Amyloid Neuropathies, Familial/physiopathology , Amyloid Neuropathies, Familial/blood , Amyloid Neuropathies, Familial/therapy , Exercise Test/methods , Cardiomyopathies/physiopathology , Cardiomyopathies/diagnosis , Cardiomyopathies/etiology , Cardiomyopathies/blood , Follow-Up Studies , Aged, 80 and over , Time Factors , Predictive Value of TestsABSTRACT
The aim of this study is to assess the effectiveness of conventional and two additional functional markers derived from standard cardiac magnetic resonance (CMR) images in detecting the occurrence of late gadolinium enhancement (LGE) in patients with secondary cardiac amyloidosis (CA) related to multiple myeloma (MM). This study retrospectively included 32 patients with preserved ejection fraction (EF) who had MM-CA diagnosed consecutively. Conventional left ventricular (LV) function markers and two additional functional markers, namely myocardial contraction fraction (MCF) and LV long-axis strain (LAS), were obtained using commercial cardiac post-processing software. Logistic regression analyses and receiver operating characteristic (ROC) analysis were performed to evaluate the predictive performances. (1) There were no notable distinctions in clinical features between the LGE+ and LGE- groups, with the exception of a reduced systolic blood pressure in the former (105.60 ± 18.85 mmHg vs. 124.50 ± 20.95 mmHg, P = 0.022). (2) Patients with MM-CA presented with intractable heart failure with preserved ejection fraction (HFpEF). The LVEF in the LGE+ group exhibited a greater reduction (54.27%, IQR 51.59-58.39%) in comparison to the LGE- group (P < 0.05). And MM-CA patients with LGE+ had significantly higher LVMI (90.15 ± 23.69 g/m2), lower MCF (47.39%, IQR 34.28-54.90%), and the LV LAS were more severely damaged (- 9.94 ± 3.42%) than patients with LGE- (all P values < 0.05). (3) The study found that MCF exhibited a significant independent association with LGE, as indicated by an odds ratio of 0.89 (P < 0.05). The cut-off value for MCF was determined to be 64.25% with a 95% confidence interval ranging from 0.758 to 0.983. The sensitivity and specificity of this association were calculated to be 95% and 83%, respectively. MCF is a simple reproducible predict marker of LGE in MM-CA patients. It is a potentially CMR-based method that promise to reduce scan times and costs, and boost the accessibility of CMR.
Subject(s)
Amyloidosis , Gadolinium , Multiple Myeloma , Myocardial Contraction , Humans , Multiple Myeloma/diagnostic imaging , Multiple Myeloma/complications , Multiple Myeloma/pathology , Female , Male , Aged , Middle Aged , Amyloidosis/diagnostic imaging , Amyloidosis/physiopathology , Amyloidosis/pathology , Retrospective Studies , Stroke Volume , Ventricular Function, Left , Contrast Media , Magnetic Resonance Imaging/methods , Cardiomyopathies/diagnostic imaging , Cardiomyopathies/physiopathology , Cardiomyopathies/etiology , ROC Curve , Magnetic Resonance Imaging, Cine/methodsABSTRACT
Sepsis-induced myocardial depression (SIMD), a common complication of sepsis, is one of the main causes of death in patients with sepsis. The pathogenesis of SIMD is complicated, and the process of SIMD remains incompletely understood, with no single or definitive mechanism fully elucidated. Notably, pyroptosis, as a pro-inflammatory programmed cell death, is characterized by Gasdermin-mediated formation of pores on the cell membrane, cell swelling, and cell rupture accompanied by the release of large amounts of inflammatory factors and other cellular contents. Mechanistically, pyroptosis is mainly divided into the canonical pathway mediated by caspase-1 and the non-canonical pathway mediated by caspase-4/5/11. Pyroptosis has been confirmed to participate in various inflammation-associated diseases. In recent years, more and more studies have shown that pyroptosis is also involved in the occurrence and development of SIMD. This article reviews the molecular mechanisms of pyroptosis and its research progress in SIMD, aiming to provide novel strategies and targets for the treatment of SIMD.
Subject(s)
Pyroptosis , Sepsis , Humans , Sepsis/complications , Animals , Cardiomyopathies/etiologyABSTRACT
Arrhythmogenic cardiomyopathy (ACM) is a familial heart disease characterized by cardiac dysfunction, arrhythmias, and myocardial inflammation. Exercise and stress can influence the disease's progression. Thus, an investigation of whether a high-fat diet (HFD) contributes to ACM pathogenesis is warranted. In a robust ACM mouse model, 8-week-old Desmoglein-2 mutant (Dsg2mut/mut) mice were fed either an HFD or rodent chow for 8 weeks. Chow-fed wildtype (WT) mice served as controls. Echo- and electrocardiography images pre- and post-dietary intervention were obtained, and the lipid burden, inflammatory markers, and myocardial fibrosis were assessed at the study endpoint. HFD-fed Dsg2mut/mut mice showed numerous P-wave perturbations, reduced R-amplitude, left ventricle (LV) remodeling, and reduced ejection fraction (%LVEF). Notable elevations in plasma high-density lipoprotein (HDL) were observed, which correlated with the %LVEF. The myocardial inflammatory adipokines, adiponectin (AdipoQ) and fibroblast growth factor-1, were substantially elevated in HFD-fed Dsg2mut/mut mice, albeit no compounding effect was observed in cardiac fibrosis. The HFD not only potentiated cardiac dysfunction but additionally promoted adverse cardiac remodeling. Further investigation is warranted, particularly given elevated AdipoQ levels and the positive correlation of HDL with the %LVEF, which may suggest a protective effect. Altogether, the HFD worsened some, but not all, disease phenotypes in Dsg2mut/mut mice. Notwithstanding, diet may be a modifiable environmental factor in ACM disease progression.