DONA ORA
Pubblicazioni recenti - dilated cardiomyopathy
-
Metabolic Profiling Associates with Disease Severity in Non-Ischemic Dilated Cardiomyopathy.
J Card Fail2019 Sep;():. doi: S1071-9164(19)30210-6.
Verdonschot Job A J, Wang Ping, van Bilsen Marc, Hazebroek Mark R, Merken Jort J, Vanhoutte Els K, Henkens Michiel T H M, van den Wijngaard Arthur, Glatz Jan F C, Krapels Ingrid P C, Brunner Han G, Heymans Stephane R B, Bierau Jörgen,
Abstract
AIMS:
Metabolomic profiling may have diagnostic and prognostic value in heart failure. This study investigated whether targeted blood and urine metabolomics reflects disease severity in non-ischemic dilated cardiomyopathy (DCM) patients and compared its incremental value on top of NT-proBNP.
METHODS AND RESULTS:
A total of 149 metabolites were measured in plasma and urine samples of 273 DCM patients with different stages of disease (DCM patients with LVRR (normal LVEF), n=70; asymptomatic DCM, n=72 and symptomatic DCM, n=131). Acylcarnitines, sialic acid, and glutamic acid are the most distinctive metabolites associated with disease severity, as repeatedly revealed by uni-biomarker linear regression, sPLSDA, Random Forest and conditional Random Forest analyses. However, the absolute difference of the metabolic profile among groups was marginal. A decision tree model based on the top metabolites did not surpass NT-proBNP in classifying stages. However, a combination of NT-proBNP and the top metabolites improved the decision tree to distinguish DCM patients with LVRR from symptomatic DCM (AUC 0.813±0.138 versus 0.739±0.114; p=0.02).
CONCLUSION:
Functional cardiac recovery is reflected in metabolomics. These alterations reveal potential alternative treatment targets in advanced symptomatic DCM. The metabolic profile can complement NT-proBNP in determining disease severity in non-ischemic DCM.
Copyright © 2019. Published by Elsevier Inc.
Guarda su PubMed
-
Umbilical cord-derived mesenchymal stromal cells in cardiovascular disease: review of preclinical and clinical data.
Cytotherapy2019 Sep;():. doi: S1465-3249(19)30462-1.
Collichia Martina, Jones Daniel A, Beirne Anne-Marie, Hussain Mohsin, Weeraman Deshan, Rathod Krishnaraj, Veerapen Jessry, Lowdell Mark, Mathur Anthony,
Abstract
The human umbilical cord has recently emerged as an attractive potential source of mesenchymal stromal cells (MSCs) to be adopted for use in regenerative medicine. Umbilical cord MSCs (UC-MSCs) not only share the same features of all MSCs such as multi-lineage differentiation, paracrine functions and immunomodulatory properties, they also have additional advantages, such as no need for bone marrow aspiration and higher self-renewal capacities. They can be isolated from various compartments of the umbilical cord (UC) and can be used for autologous or allogeneic purposes. In the past decade, they have been adopted in cardiovascular disease and have shown promising results mainly due to their pro-angiogenic and anti-inflammatory properties. This review offers an overview of the biological properties of UC-MSCs describing available pre-clinical and clinical data with respect to their potential therapeutic use in cardiovascular regeneration, with current challenges and future directions discussed.
Copyright © 2019 International Society for Cell and Gene Therapy. Published by Elsevier Inc. All rights reserved.
Guarda su PubMed
-
Life-threatening muscle complications of COL4A1-related disorder.
Brain Dev2019 Sep;():. doi: S0387-7604(19)30293-1.
Okano Satomi, Shimada Sorachi, Tanaka Ryosuke, Okayama Akie, Kajihama Aya, Suzuki Nao, Nakau Koichi, Takahashi Satoru, Matsumoto Naomichi, Saitsu Hirotomo, Tanboon Jantima, Nishino Ichizo, Azuma Hiroshi,
Abstract
COL4A1-related disorder is recognized as a systemic disease because the alpha 1 chain of type IV collagen, encoded by COL4A1, is essential for basement membrane stability. However, muscular manifestations related to this disorder are rarely reported. We report the case of a 2-year-old boy with porencephaly, who harbored a de novo COL4A1 mutation of c.1853G?>?A, p. (Gly618Glu) and exhibited recurrent rhabdomyolysis with viral or bacterial infections. Moreover, he developed obstructive hypertrophic cardiomyopathy which required surgical intervention. Skeletal muscle biopsy revealed findings compatible with fiber-type disproportion. Ultrastructural study demonstrated the similar findings previously reported in mice with Col4a1 mutation including collagen disarray and reduction of electron density in the basement membrane of capillary endothelial cells and muscle fibers. Dilated endoplasmic reticulum in the capillary endothelial cells is also noted. This report adds another disease spectrum of COL4A1 mutation which include porencephaly, hypertrophic cardiomyopathy, rhabdomyolysis and fiber-type disproportion.
Copyright © 2019 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
Guarda su PubMed
-
Battle of the Sexes: Differential Prognosis by Sex in Dilated Cardiomyopathy.
Can J Cardiol2019 Jul;():. doi: S0828-282X(19)30469-6.
Yogasundaram Haran, Qi Arthur, Nguyen Quynh, Oudit Gavin Y,
Guarda su PubMed
-
Dilated cardiomyopathy and rhabdomyolysis caused by hypopituitarism: a challenging diagnosis.
Acta Cardiol2019 Sep;():1-5. doi: 10.1080/00015385.2019.1665848.
Verhoestraete Pauwelijn, Marijn Carpentier, Jan Donck, Hans Vandekerckhove,
Guarda su PubMed
-
KCNT1 epilepsy with migrating focal seizures shows a temporal sequence with poor outcome, high mortality and SUDEP.
Brain2019 Aug;():. doi: awz240.
Kuchenbuch Mathieu, Barcia Giulia, Chemaly Nicole, Carme Emilie, Roubertie Agathe, Gibaud Marc, Van Bogaert Patrick, de Saint Martin Anne, Hirsch Edouard, Dubois Fanny, Sarret Catherine, Nguyen The Tich Sylvie, Laroche Cecile, des Portes Vincent, Billette de Villemeur Thierry, Barthez Marie-Anne, Auvin Stéphane, Bahi-Buisson Nadia, Desguerre Isabelle, Kaminska Anna, Benquet Pascal, Nabbout Rima,
Abstract
Epilepsy of infancy with migrating focal seizures was first described in 1995. Fifteen years later, KCNT1 gene mutations were identified as the major disease-causing gene of this disease. Currently, the data on epilepsy of infancy with migrating focal seizures associated with KCNT1 mutations are heterogeneous and many questions remain unanswered including the prognosis and the long-term outcome especially regarding epilepsy, neurological and developmental status and the presence of microcephaly. The aim of this study was to assess data from patients with epilepsy in infancy with migrating focal seizures with KCNT1 mutations to refine the phenotype spectrum and the outcome. We used mind-maps based on medical reports of children followed in the network of the French reference centre for rare epilepsies and we developed family surveys to assess the long-term outcome. Seventeen patients were included [age: median (25th-75th percentile): 4 (2-15) years, sex ratio: 1.4, length of follow-up: 4 (2-15) years]. Seventy-one per cent started at 6 (1-52) days with sporadic motor seizures (n = 12), increasing up to a stormy phase with long lasting migrating seizures at 57 (30-89) days. The others entered this stormy phase directly at 1 (1-23) day. Ten patients entered a consecutive phase at 1.3 (1-2.8) years where seizures persisted at least daily (n = 8), but presented different semiology: brief and hypertonic with a nocturnal (n = 6) and clustered (n = 6) aspects. Suppression interictal patterns were identified on the EEG in 71% of patients (n = 12) sometimes from the first EEG (n = 6). Three patients received quinidine without reported efficacy. Long-term outcome was poor with neurological sequelae and active epilepsy except for one patient who had an early and long-lasting seizure-free period. Extracerebral symptoms probably linked with KCNT1 mutation were present, including arteriovenous fistula, dilated cardiomyopathy and precocious puberty. Eight patients (47%) had died at 3 (1.5-15.4) years including three from suspected sudden unexpected death in epilepsy. Refining the electro-clinical characteristics and the temporal sequence of epilepsy in infancy with migrating focal seizures should help diagnosis of this epilepsy. A better knowledge of the outcome allows one to advise families and to define the appropriate follow-up and therapies. Extracerebral involvement should be investigated, in particular the cardiac system, as it may be involved in the high prevalence of sudden unexpected death in epilepsy in these cases.
© The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Guarda su PubMed
-
[Two cases with dilated cardiomyopathy since infancy].
Zhonghua Er Ke Za Zhi2019 Sep;57(9):712-714. doi: 10.3760/cma.j.issn.0578-1310.2019.09.013.
Li Y Y, Feng Y J, Wang F J, Yao X L, Hou W N, Li D X,
Guarda su PubMed
-
Wilms tumor with dilated cardiomyopathy: A case report.
World J Clin Oncol2019 Aug;10(8):293-299. doi: 10.5306/wjco.v10.i8.293.
Sethasathien Saviga, Choed-Amphai Chane, Saengsin Kwannapas, Sathitsamitphong Lalita, Charoenkwan Pimlak, Tepmalai Kanokkan, Silvilairat Suchaya,
Abstract
BACKGROUND:
Wilms tumor is the most common renal malignancy in childhood. It occurs primarily between the ages of 2 and 5 years. The usual manifestations are abdominal mass, hypertension, and hematuria. The case presented here had an unusual presentation, with dilated cardiomyopathy and hypertension secondary to the Wilms tumor.
CASE SUMMARY:
A 3-year-old boy presented with a 5-d history of irritability, poor appetite, and respiratory distress. His presenting clinical symptoms were dyspnea, tachycardia, hypertension, and a palpable abdominal mass at the left upper quadrant. His troponin T and pro-B-type natriuretic peptide levels were elevated. Echocardiography demonstrated a dilated hypokinetic left ventricle with an ejection fraction of 29%, and a suspected left renal mass. Computed tomography scan revealed a left renal mass and multiple lung nodules. The definitive diagnosis of Wilms tumor was confirmed histologically. The patient was administered neoadjuvant chemotherapy and underwent radical nephrectomy. After surgery, radiotherapy was administered, and the adjuvant chemotherapy was continued. The blood pressure and left ventricular function normalized after the treatments.
CONCLUSION:
Abdominal mass, dilated cardiomyopathy and hypertension can indicate Wilms tumor in pediatric patients. Chemotherapy and tumor removal achieve successful treatment.
Guarda su PubMed
-
Ecstasy induced acute systolic heart failure and Non-Ischemic Cardiomyopathy in a young female: a rare case report and literature review.
J Community Hosp Intern Med Perspect2019 ;9(4):336-339. doi: 10.1080/20009666.2019.1650593.
Kafle Paritosh, Shrestha Binav, Mandal Amrendra, Sharma Dikshya, Bhandari Manjul, Amgai Birendra, Khalid Mazin, Sidhu Jasdeep S, Solaimanzadeh Isaac, Gayam Vijay, Surana Rahul, Dufresne Alix,
Abstract
Ecstasy or 3,4-methylenedioxymethamphetamine (MDMA) is an illicit recreational drug. Effects include euphoria, increased sensory awareness, and central stimulation. Although various arrhythmias, as well as dilated cardiomyopathy, have been previously noted to occur with chronic use, cardiac toxicities are seldom reported in an acute setting. Herein, we present a 28-year-old female patient with no prior medical condition that presented to the Emergency Department with chest pain following intake of MDMA. Electrocardiographic findings, as well as laboratories, were suggestive of possible Acute Non-ST elevation myocardial infarction. Upon admission, cardiac catheterization revealed patent coronary arteries. Stark regional wall motion abnormalities were observed along with reduced ejection fraction. Acute systolic heart failure was treated with standard medical management. Subsequent reassessment of ventricular function with Echocardiography revealed marked improvement. This article describes a case of MDMA induced heart failure, including details of evaluation, management, and monitoring of patient progress. It brings further attention to potential acute harmful effects of MDMA on cardiac function and viability.
Guarda su PubMed
-
Clinical utility of exome sequencing in infantile heart failure.
Genet Med2019 Sep;():. doi: 10.1038/s41436-019-0654-3.
Ritter Alyssa, Bedoukian Emma, Berger Justin H, Copenheaver Deborah, Gray Christopher, Krantz Ian, Izumi Kosuke, Juusola Jane, Leonard Jacqueline, Lin Kimberly, Medne Livija, Santani Avni, Skraban Cara, Yang Sandra, Ahrens-Nicklas Rebecca C,
Abstract
PURPOSE:
Pediatric cardiomyopathy is rare, has a broad differential diagnosis, results in high morbidity and mortality, and has suboptimal diagnostic yield using next-generation sequencing panels. Exome sequencing has reported diagnostic yields ranging from 30% to 57% for neonates in intensive care units. We aimed to characterize the clinical utility of exome sequencing in infantile heart failure.
METHODS:
Infants diagnosed with acute heart failure prior to 1 year old over a period of 34 months at a large tertiary children's hospital were recruited. Demographic and diagnostic information was obtained from medical records. Fifteen eligible patients were enrolled.
RESULTS:
Dilated cardiomyopathy was the predominant cardiac diagnosis, seen in 60% of patients. A molecular diagnosis was identified in 66.7% of patients (10/15). Of those diagnoses, 70% would not have been detected using multigene next-generation sequencing panels focused on cardiomyopathy or arrhythmia disease genes. Genetic testing changed medical decision-making in 53% of all cases and 80% of positive cases, and was especially beneficial when testing was expedited.
CONCLUSION:
Given the broad differential diagnosis and critical status of infants with heart failure, rapid exome sequencing provides timely diagnoses, changes medical management, and should be the first-tier molecular test.
Guarda su PubMed
-
Prognostic Impact of Atrial Fibrillation in Electrical Storm.
Cardiology2019 Sep;():1-9. doi: 10.1159/000500262.
Müller Julian, Behnes Michael, Ellguth Dominik, Schupp Tobias, Taton Gabriel, Reiser Linda, Engelke Niko, Reichelt Thomas, Bollow Armin, Kim Seung-Hyun, Barth Christian, Rusnak Jonas, Weidner Kathrin, Mashayekhi Kambis, Akin Muharrem, Bertsch Thomas, Weiß Christel, Borggrefe Martin, Akin Ibrahim,
Abstract
BACKGROUND:
Data regarding the prognostic impact of atrial fibrillation (AF) in patients with electrical storm (ES) is rare.
OBJECTIVES:
This study sought to assess the prognostic impact of AF in patients with ES on mortality, rehospitalization, major adverse cardiovascular events (MACE) and recurrence of ES (ES-R).
METHODS:
All consecutive implantable cardioverter defibrillator (ICD) patients presenting with ES were included retrospectively from 2002 to 2016. Patients with AF were compared to non-AF patients. The primary prognostic endpoint was all-cause mortality. Secondary endpoints were in-hospital mortality, rehospitalization rates, MACE and ES-R.
RESULTS:
A total of 87 ES patients with ICD were included and followed up to 2.5 years; 43% suffered from AF. The presence of AF was associated with increased all-cause mortality (47 vs. 29%, log-rank p = 0.052; hazard ratio [HR] 1.969, 95% confidence interval [CI] 0.981-3.952, p = 0.057), which was no longer present after multivariable adjustment for age, diabetes and dilated cardiomyopathy. Furthermore, AF was associated with increased rates of overall rehospitalization (61 vs. 31%, log-rank p = 0.013; HR 2.381, 95% CI 1.247-4.547, p = 0.009), especially due to AF (14 vs. 0%, p = 0.001) and acute heart failure (AHF) (28 vs. 10%, p = 0.018; HR 3.754, 95% CI 1.277-11.038, p = 0.016). Notably, AF was not associated with differences in MACE (55 vs. 37%, log rank p = 0.339) and ES-R (28 vs. 25%, log rank p = 0.704).
CONCLUSION:
In ES patients, presence of AF was univariably associated with increased rates of all-cause mortality at 2.5 years. Furthermore, AF was multivariably associated with overall rehospitalization, especially due to AF and AHF.
© 2019 S. Karger AG, Basel.
Guarda su PubMed
-
Glycogen storage disease type IV: dilated cardiomyopathy as the isolated initial presentation in an adult patient.
BMJ Case Rep2019 Sep;12(9):. doi: e230068.
Ndugga-Kabuye Mesaki Kenneth, Maleszewski Joseph, Chanprasert Sirisak, Smith Kelly D,
Abstract
Glycogen storage disease type IV (GSD IV, Andersen disease) is a rare autosomal recessive condition. The childhood neuromuscular subtype of GSD IV is characterised by a progressive skeletal myopathy with cardiomyopathy also reported in some individuals. We report a case of a 19-year-old man who presented with severe non-ischaemic dilated cardiomyopathy (NIDCM) necessitating heart transplantation, with biopsy showing aggregations of polyglucosan bodies in cardiac myocytes. He had no signs or symptoms of muscle weakness, liver dysfunction or neurologic involvement. A homozygous c.607C>A (p.His203Asn) variant was identified. Our case is unusual in that our patient presented with an isolated NIDCM in the absence of other clinical manifestations of GSD IV. This case highlights the importance of considering storage disorders in young adults presenting with isolated NIDCM of unknown aetiology. It also emphasises the potential synergy between histopathological evaluation and genomic testing in enhancing diagnostic certainty.
© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.
Guarda su PubMed
-
Cost-Utility of Wearable Cardioverter Defibrillators in Children with Dilated Cardiomyopathy during Medical Optimization: Is it Worth the Wait?
Heart Rhythm -
Present criteria for prophylactic ICD implantation: Insights from the EU-CERT-ICD (Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter Defibrillators in EUrope) project.
J Electrocardiol2019 Sep;():. doi: S0022-0736(19)30415-7.
Zabel Markus, Schlögl Simon, Lubinski Andrzej, Svendsen Jesper Hastrup, Bauer Axel, Arbelo Elena, Brusich Sandro, Conen David, Cygankiewicz Iwona, Dommasch Michael, Flevari Panagiota, Galuszka Jan, Hansen Jim, Hasenfuß Gerd, Hatala Robert, Huikuri Heikki V, Kenttä Tuomas, Kucejko Tomasz, Haarmann Helge, Harden Markus, Iovev Svetoslav, Kääb Stefan, Kaliska Gabriela, Katsimardos Andreas, Kasprzak Jaroslaw D, Qavoq Dariusz, Lüthje Lars, Malik Marek, Novotný Tomá?, Pavlovi? Nikola, Perge Peter, Röver Christian, Schmidt Georg, Shalganov Tchavdar, Sritharan Rajeeva, Svetlosak Martin, Sallo Zoltan, Szavits-Nossan Janko, Traykov Vassil, Vandenberk Bert, Velchev Vasil, Vos Marc A, Willich Stefan N, Friede Tim, Willems Rik, Merkely Béla, Sticherling Christian, ,
Abstract
BACKGROUND:
The clinical effectiveness of primary prevention implantable cardioverter defibrillator (ICD) therapy is under debate. It is urgently needed to better identify patients who benefit from prophylactic ICD therapy. The EUropean Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter Defibrillators (EU-CERT-ICD) completed in 2019 will assess this issue.
SUMMARY:
The EU-CERT-ICD is a prospective investigator-initiated non-randomized, controlled, multicenter observational cohort study done in 44 centers across 15 European countries. A total of 2327 patients with heart failure due to ischemic heart disease or dilated cardiomyopathy indicated for primary prophylactic ICD implantation were recruited between 2014 and 2018 (>1500 patients at first ICD implantation, >750 patients non-randomized non-ICD control group). The primary endpoint was all-cause mortality, and first appropriate shock was co-primary endpoint. At baseline, all patients underwent 12?lead ECG and Holter-ECG analysis using multiple advanced methods for risk stratification as well as documentation of clinical characteristics and laboratory values. The EU-CERT-ICD data will provide much needed information on the survival benefit of preventive ICD therapy and expand on previous prospective risk stratification studies which showed very good applicability of clinical parameters and advanced risk stratifiers in order to define patient subgroups with above or below average ICD benefit.
CONCLUSION:
The EU-CERT-ICD study will provide new and current data about effectiveness of primary prophylactic ICD implantation. The study also aims for improved risk stratification and patient selection using clinical risk markers in general, and advanced ECG risk markers in particular.
Copyright © 2019. Published by Elsevier Inc.
Guarda su PubMed
-
Double missense mutations in cardiac myosin-binding protein C and myopalladin genes: A case report with diffuse coronary disease, complete atrioventricular block, and progression to dilated cardiomyopathy.
Ann Noninvasive Electrocardiol2019 Sep;():e12687. doi: 10.1111/anec.12687.
Mastroianno Sandra, Palumbo Pietro, Castellana Stefano, Leone Maria Pia, Massaro Raimondo, Potenza Domenico Rosario, Mazza Tommaso, Russo Aldo, Castori Marco, Carella Massimo, Di Stolfo Giuseppe,
Abstract
Cardiomyopathies caused by double gene mutations are rare but conferred a remarkably increased risk of end-stage progression, arrhythmias, and poor outcome. Compound genetic mutations leading to complex phenotype in the setting of cardiomyopathies represent an important challenge in clinical practice, and genetic tests allow risk stratification and personalized clinical management of patients. We report a case of a 50-year-old woman with congestive heart failure characterized by dilated cardiomyopathy, diffuse coronary disease, complete atrioventricular block, and missense mutations in cardiac myosin-binding protein C (MYBPC3) and myopalladin (MYPN). We discuss the plausible role of genetic profile in phenotype determination.
© 2019 Wiley Periodicals, Inc.
Guarda su PubMed
-
Genetic Arrhythmias Complicating Patients with Dilated Cardiomyopathy.
Heart Rhythm2019 Sep;():. doi: S1547-5271(19)30833-1.
Li Zongzhe, Chen Peng, Li Chenze, Tan Lun, Xu Jinchao, Wang Hong, Sun Yang, Wang Yan, Zhao Chunxia, Link Mark S, Wilde Arthur A M, Wang Dao Wu, Wang Dao Wen,
Abstract
BACKGROUND:
Sudden cardiac death due to malignant arrhythmias is a common cause of death in dilated cardiomyopathy (DCM). Whether genetic variants increase the risk of arrhythmias in DCM is unknown.
OBJECTIVES:
To investigate the genetic causes of arrhythmias in DCM patients.
METHODS:
Whole-exome sequencing (WES) and high-depth targeted next-generation sequencing (142-gene panel) were utilized. Eight specific DCM pedigrees with arrhythmias and two separate cohorts of 1232 consecutive unrelated sporadic DCM patients from three medical centers (550 in the discovery cohort; 682 in the replication cohort) were analyzed; 470 (250 in the discovery cohort; 220 in the replication cohort) suffered from arrhythmias (DCM-A group) and 762 (300 in the discovery cohort; 462 in the replication cohort) did not (DCM-NA group). All identified causative variants were Sanger sequenced to eliminate false-positive results and then screened in 700 unrelated matched arrhythmia- and DCM-free healthy controls.
RESULTS:
We identified LQTS-causative variants that independently cosegregated in two unrelated DCM-LQTS pedigrees. Pathogenic variants in arrhythmia-related genes (Ion-channelopathies) were identified in 4.9% (23/470) of sporadic DCM-A patients (4.0% in the discovery cohort and 5.9% in the replication cohort) but only 0.1% (1/762) of sporadic DCM-NA patients (P=2.16 × 10). These arrhythmia-related pathogenic variants included long QT syndrome, atrial fibrillation, sick sinus syndrome, cardiac conduction disease, and Brugada syndrome.
CONCLUSIONS:
Some arrhythmias in DCM patients are caused by arrhythmia-related pathogenic variants. For DCM patients with explicit arrhythmias, arrhythmia-causative genetic screening may help to explain the etiology and decision making.
Copyright © 2019. Published by Elsevier Inc.
Guarda su PubMed
-
Differential expression of genes participating in cardiomyocyte electrophysiological remodeling via membrane ionic mechanisms and Ca-handling in human heart failure.
Mol Cell Biochem2019 Sep;():. doi: 10.1007/s11010-019-03626-4.
Kepenek Eda Seyma, Ozcinar Evren, Tuncay Erkan, Akcali Kamil Can, Akar Ahmet Ruchan, Turan Belma,
Abstract
Excitation-contraction coupling in normal cardiac function is performed with well balanced and coordinated functioning but with complex dynamic interactions between functionally connected membrane ionic currents. However, their genomic investigations provide essential information on the regulation of diseases by their transcripts. Therefore, we examined the gene expression levels of the most important voltage-gated ionic channels such as Na-channels (SCN5A), Ca-channels (CACNA1C and CACNA1H), and K-channels, including transient outward (KCND2, KCNA2, KCNA5, KCNA8), inward rectifier (KCNJ2, KCNJ12, KCNJ4), and delayed rectifier (KCNB1) in left ventricular tissues from either ischemic or dilated cardiomyopathy (ICM or DCM). We also examined the mRNA levels of ATP-dependent K-channels (KCNJ11, ABCC9) and ERG-family channels (KCNH2). We further determined the mRNA levels of ryanodine receptors (RyR2; ARVC2), phospholamban (PLB or PLN), SR Ca-pump (SERCA2; ATP2A1), an accessory protein FKBP12 (PPIASE), protein kinase A (PPNAD4), and Ca/calmodulin-dependent protein kinase II (CAMK2G). The mRNA levels of SCN5A, CACNA1C, and CACNA1H in both groups decreased markedly in the heart samples with similar significance, while KvLQT1 genes were high with depressed Kv4.2. The KCNJ11 and KCNJ12 in both groups were depressed, while the KCNJ4 level was significantly high. More importantly, the KCNA5 gene was downregulated only in the ICM, while the KCNJ2 was upregulated only in the DCM. Besides, mRNA levels of ARVC2 and PLB were significantly high compared to the controls, whereas others (ATP2A1, PPIASE, PPNAD4, and CAMK2G) were decreased. Importantly, the increases of KCNB1 and KCNJ11 were more prominent in the ICM than DCM, while the decreases in ATP2A1 and FKBP1A were more prominent in DCM compared to ICM. Overall, this study was the first to demonstrate that the different levels of changes in gene profiles via different types of cardiomyopathy are prominent particularly in some K-channels, which provide further information about our knowledge of how remodeling processes can be differentiated in HF originated from different pathological conditions.
Guarda su PubMed
-
Hypocalcemic cardiomyopathy: a rare presenting manifestation of hypoparathyroidism.
BMJ Case Rep2019 Sep;12(9):. doi: e229822.
Saini Neharika, Mishra Sanat, Banerjee Saurav, Rajput Rajesh,
Abstract
Hypoparathyroidism patients present with features of hypocalcemia like carpopedal spasm, numbness and paresthesias but hypocalcemic cardiomyopathy leading to congestive heart failure (CHF) is a rare presentation. We present here a case of 55-year-old Asian man who was a known case of dilated cardiomyopathy for 6 months, presented with the chief complaints of shortness of breath on exertion and decreased urine output. On general physical examination, features suggestive of CHF were seen. Chvostek and Trousseau's sign was positive. The patient had a history of cataract surgery of both eyes 15 years ago. Further investigations revealed hypocalcemia. Echo showed severe global hypokinesia of left ventricle with left ventricle ejection fraction 15%. This CHF was refractory to conventional treatment, though, with calcium supplementation, the patient improved symptomatically. On follow-up after 3 months, an improvement was seen in the echocardiographic parameters with ejection fraction improving to 25%.
© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.
Guarda su PubMed
-
Disruption of cardiac thin filament assembly arising from a mutation in : A novel mechanism of neonatal dilated cardiomyopathy.
Sci Adv2019 Sep;5(9):eaax2066. doi: 10.1126/sciadv.aax2066.
Ahrens-Nicklas Rebecca C, Pappas Christopher T, Farman Gerrie P, Mayfield Rachel M, Larrinaga Tania M, Medne Livija, Ritter Alyssa, Krantz Ian D, Murali Chaya, Lin Kimberly Y, Berger Justin H, Yum Sabrina W, Carreon Chrystalle Katte, Gregorio Carol C,
Abstract
Neonatal heart failure is a rare, poorly-understood presentation of familial dilated cardiomyopathy (DCM). Exome sequencing in a neonate with severe DCM revealed a homozygous nonsense variant in leiomodin 2 (, p.Trp398*). Leiomodins (Lmods) are actin-binding proteins that regulate actin filament assembly. While disease-causing mutations in smooth () and skeletal () muscle isoforms have been described, the cardiac () isoform has not been previously associated with human disease. Like our patient, -null mice have severe early-onset DCM and die before weaning. The infant's explanted heart showed extraordinarily short thin filaments with isolated cardiomyocytes displaying a large reduction in maximum calcium-activated force production. The lack of extracardiac symptoms in -null mice, and remarkable morphological and functional similarities between the patient and mouse model informed the decision to pursue cardiac transplantation in the patient. To our knowledge, this is the first report of aberrant cardiac thin filament assembly associated with human cardiomyopathy.
Guarda su PubMed
-
Native T1 time and extracellular volume fraction in differentiation of normal myocardium from non-ischemic dilated and hypertrophic cardiomyopathy myocardium: A systematic review and meta-analysis.
Int J Cardiol Heart Vasc2019 Dec;25():100422. doi: 10.1016/j.ijcha.2019.100422.
Minegishi Shintaro, Kato Shingo, Takase-Minegishi Kaoru, Horita Nobuyuki, Azushima Kengo, Wakui Hiromichi, Ishigami Tomoaki, Kosuge Masami, Kimura Kazuo, Tamura Kouichi,
Abstract
Background:
Both native T1 time and extracellular volume (ECV) fraction have been shown to be important measures for the detection of myocardial fibrosis. However, ECV determination requires the administration of an intravenous contrast agent, whereas native T1 mapping can be performed without a contrast agent.
Methods:
Here, we conducted a meta-analysis of myocardial native T1 data obtained for non-ischemic cardiomyopathy (NIC) patients and controls. A literature review included studies that applied T1 mapping using modified Look-Locker inversion recovery to measure myocardial fibrosis, and the results were validated by comparing datasets for dilated cardiomyopathy (DCM) or hypertrophic cardiomyopathy (HCM) patients and healthy controls (HCs).
Results:
We identified 16 eligible studies. Pooled mean differences (MDs) and 95% confidence intervals (CIs) were estimated as follows. Native T1 at 1.5-T, DCM vs. HC: MD?=?45.26 (95% CI: 30.92-59.59); HCM vs. HC: MD?=?47.09 (95% CI: 32.42-61.76). Native T1 at 3.0-T, DCM vs. HC: MD?=?82.52 (95% CI: 47.60-117.44); HCM vs. HC: MD?=?115.87 (95% CI: 50.71-181.04). ECV at 1.5-T, DCM vs. HC: MD?=?4.26 (95% CI: 3.06-5.46); HCM vs. HC: MD?=?1.49 (95% CI: -1.45-4.43). ECV at 3.0-T, DCM vs. HC: MD?=?8.40 (95% CI: 2.94-13.86); HCM vs. HC: MD?=?8.02 (95% CI: 5.45-1-0.59).
Conclusion:
In conclusion, native T1 values were significantly different between NIC patients and controls. Native T1 mapping may be a useful noninvasive method to detect diffuse myocardial fibrosis in NIC patients.
Guarda su PubMed
