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Pubblicazioni recenti - dilated cardiomyopathy
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Estimation of increased pulmonary wedge pressure by an algorithm based on noninvasively measured pulmonary diastolic pressure in cardiac patients independent of left ventricular ejection fraction.
Echocardiography2020 Feb;():. doi: 10.1111/echo.14581.
Barbier Paolo, Cucco Cuono, Guglielmo Marco, Simioniuc Anca, Fabiani Iacopo, Pugliese Nicola Riccardo, Savioli Gabriele, Dini Frank Lloyd,
Abstract
AIM:
Pulmonary artery diastolic pressure (PADP) correlates closely with pulmonary wedge pressure (PAWP); therefore, we sought to evaluate whether an algorithm based on PADP assessment by the Doppler pulmonary regurgitation (PR) end-diastolic gradient (PRG) may aid in estimating increased PAWP in cardiac patients with reduced or preserved left ventricular (LV) ejection fraction (EF).
METHODS AND RESULTS:
Right heart catheterization, with estimation of PAWP, right atrial pressure (RAP), PADP, and Doppler echocardiography, was carried out in 183 patients with coronary artery disease (n = 63), dilated cardiomyopathy (n = 52), or aortic stenosis (n = 68). One-hundred and seventeen patients had LV EF <50%. We measured the pressure gradients across the tricuspid and pulmonary valves from tricuspid regurgitation (TRV) and PR velocities. Doppler-estimated PADP (e-PADP) was obtained by adding the estimated RAP to PRG. An algorithm based on e-PADP to predict PAWP, that included TRV, left atrial volume index, and mitral E/A, was developed and validated in derivation (n = 90) and validation (n = 93) subgroups. Both invasive PADP (r = .92, P < .001) and e-PADP (r = .72, P < .001) correlated closely with PAWP, and e-PADP predicted PAWP (AUC: 0.85, CI: 0.79-0.91) with a 94% positive predictive value (PPV) and a 55% negative predictive value (NPV), after exclusion of five patients with precapillary pulmonary hypertension. The e-PADP-based algorithm predicted PAWP with higher accuracy (PPV = 94%; NPV = 67%; accuracy = 85%; kappa: 0.65, P < .001) than the ASE-EACVI 2016 recommendations (PPV = 97%; NPV = 47%; accuracy = 68% undetermined = 18.9%; kappa: 0.15, P < .001).
CONCLUSIONS:
An algorithm based on noninvasively e-PADP can accurately predict increased PAWP in patients with cardiac disease and reduced or preserved LV EF.
© 2020 Wiley Periodicals, Inc.
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Generation of two iPSC lines (FAMRCi006-A and FAMRCi006-B) from patient with dilated cardiomyopathy and Emery-Dreifuss muscular dystrophy associated with genetic variant LMNAp.Arg527Pro.
Stem Cell Res2020 Jan;43():101714. doi: S1873-5061(20)30016-7.
Perepelina Kseniya, Klauzen Polina, Khudiakov Aleksandr, Zlotina Anna, Fomicheva Yulia, Rudenko Dmitry, Gordeev Mikhail, Sergushichev Alexey, Malashicheva Anna, Kostareva Anna,
Abstract
Mutations in LMNA gene are known to cause a broad range of diseases called laminopathies. We have generated two induced pluripotent stem cell lines FAMRCi006-A and FAMRCi006-B from a patient carrying LMNA p. p.Arg527Pro mutation associated with Emery-Dreifuss muscular dystrophy and dilated cardiomyopathy. Patient-specific peripheral blood mononuclear cells were reprogrammed to iPSCs using Sendai virus reprogramming system. Characterization of iPSCs had revealed pluripotency marker expression, normal karyotype, ability to differentiate into three embryonic germ layers. The reported iPSC lines could be a useful tool for in vitro modeling of laminopathies associated with LMNA genetic variants.
Copyright © 2020. Published by Elsevier B.V.
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Correction: Exome-wide association study reveals novel susceptibility genes to sporadic dilated cardiomyopathy.
PLoS One2020 ;15(2):e0229472. doi: 10.1371/journal.pone.0229472.
Esslinger Ulrike, Garnier Sophie, Korniat Agathe, Proust Carole, Kararigas Georgios, Müller-Nurasyid Martina, Empana Jean-Philippe, Morley Michael P, Perret Claire, Stark Klaus, Bick Alexander G, Prasad Sanjay K, Kriebel Jennifer, Li Jin, Tiret Laurence, Strauch Konstantin, O'Regan Declan P, Marguiles Kenneth B, Seidman Jonathan G, Boutouyrie Pierre, Lacolley Patrick, Jouven Xavier, Hengstenberg Christian, Komajda Michel, Hakonarson Hakon, Isnard Richard, Arbustini Eloisa, Grallert Harald, Cook Stuart A, Seidman Christine E, Regitz-Zagrosek Vera, Cappola Thomas P, Charron Philippe, Cambien François, Villard Eric,
Abstract
[This corrects the article DOI: 10.1371/journal.pone.0172995.].
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Predictors of left ventricular remodelling in patients with dilated cardiomyopathy - a cardiovascular magnetic resonance study.
Eur J Heart Fail2020 Feb;():. doi: 10.1002/ejhf.1734.
Tayal Upasana, Wage Ricardo, Newsome Simon, Manivarmane Ramasamy, Izgi Cemil, Muthumala Amal, Dungu Jason N, Assomull Ravi, Hatipoglu Suzan, Halliday Brian P, Lota Amrit S, Ware James S, Gregson John, Frenneaux Michael, Cook Stuart A, Pennell Dudley J, Scott Andrew D, Cleland John G F, Prasad Sanjay K,
Abstract
AIMS:
There is an important need for better biomarkers to predict left ventricular (LV) remodelling in dilated cardiomyopathy (DCM). We undertook a comprehensive assessment of cardiac structure and myocardial composition to determine predictors of remodelling.
METHODS AND RESULTS:
Prospective study of patients with recent-onset DCM with cardiovascular magnetic resonance (CMR) assessment of ventricular structure and function, extracellular volume (T1 mapping), myocardial strain, myocardial scar (late gadolinium enhancement) and contractile reserve (dobutamine stress). Regression analyses were used to evaluate predictors of change in LV ejection fraction (LVEF) over 12?months. We evaluated 56 participants (34 DCM patients, median LVEF 43%; 22 controls). Absolute LV contractile reserve predicted change in LVEF (1% increase associated with 0.4% increase in LVEF at 12?months, P = 0.02). Baseline myocardial strain (P = 0.39 global longitudinal strain), interstitial myocardial fibrosis (P = 0.41), replacement myocardial fibrosis (P = 0.25), and right ventricular contractile reserve (P = 0.17) were not associated with LV reverse remodelling. There was a poor correlation between contractile reserve and either LV extracellular volume fraction (r = -0.22, P = 0.23) or baseline LVEF (r = 0.07, P = 0.62). Men were more likely to experience adverse LV remodelling (P = 0.01) but age (P = 0.88) and disease-modifying heart failure medication (beta-blocker, P = 0.28; angiotensin-converting enzyme inhibitor, P = 0.92) did not predict follow-up LVEF.
CONCLUSIONS:
Substantial recovery of LV function occurs within 12?months in most patients with recent-onset DCM. Women had the greatest improvement in LVEF. A low LV contractile reserve measured by dobutamine stress CMR appears to identify patients whose LVEF is less likely to recover.
© 2020 The Authors. European Journal of Heart Failure © 2020 European Society of Cardiology.
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Emerging concepts in arrhythmogenic dilated cardiomyopathy.
Heart Fail Rev2020 Feb;():. doi: 10.1007/s10741-020-09933-z.
Zegkos Thomas, Panagiotidis Theofilos, Parcharidou Despoina, Efthimiadis Georgios,
Abstract
Dilated cardiomyopathy (DCM) represents one of the primary cardiomyopathies and may lead to heart failure and sudden death. Until recently, ventricular arrhythmias were considered to be a direct consequence of the systolic dysfunction of the left ventricle (LV) and guidelines for implantable cardioverter defibrillator implantation were established on this basis. However, the identification of heritable dilated cardiomyopathy phenotypes that presented with mildly impaired or moderate LV dysfunction, with or without chamber dilatation, and ventricular arrhythmias exceeding the degree of the underlying morphological abnormalities lead to the identification of the arrhythmogenic phenotypes and genotypes of DCM. This subset of DCM patients presents phenotypic and in many cases genotypic overlaps with left dominant arrhythmogenic cardiomyopathy (LDAC). LMNA, SCN5A, FLNC, TTN, and RBM20 are the main genes responsible for arrhythmogenic DCM. Moreover, desmosomal genes such as DSP and other non-desmosomal such as DES and PLN have been associated with both LDAC and arrhythmogenic DCM. The aim of this review is to highlight the importance of genetic profiling among DCM patients with disproportionate arrhythmic burden and the significance of the electrocardiogram, cardiac magnetic resonance, Holter monitoring, detailed family history, and other assays in order to identify red flags for arrhythmogenic DCM and proceed to an early preventive approach for sudden cardiac death. A special consideration was given to the phenotypic and genotypic overlap with LDAC. The role of myocarditis as a common disease expression of LDAC and arrhythmogenic DCM is also analyzed supporting the premise of their phenotypic overlap.
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Bridge to recovery with Berlin Heart EXCOR in children <10?kg with dilated cardiomyopathy: a histological analysis.
Eur J Cardiothorac Surg2020 Feb;():. doi: ezaa033.
Tominaga Yuji, Ueno Takayoshi, Kido Takashi, Kanaya Tomomitsu, Narita Jun, Ishida Hidekazu, Toda Koichi, Kuratani Toru, Sawa Yoshiki,
Abstract
OBJECTIVES:
This study aimed to identify the histological characteristics associated with bridge to recovery using Berlin Heart EXCOR® (BHE) in paediatric patients <10?kg with dilated cardiomyopathy.
METHODS:
Of the 10 consecutive patients <10?kg with dilated cardiomyopathy who underwent BHE implantation between 2013 and 2018, 4 patients showed improvement in left ventricular (LV) function, resulting in successful BHE explantation (recovery group). The remaining 6 patients showed persistent LV dysfunction and underwent heart transplantation (non-recovery group). The following variables were compared between the 2 groups: (i) histological findings in LV myocardium obtained at BHE implantation and (ii) LV function after BHE implantation assessed with echocardiography and cardiac catheterization.
RESULTS:
The degree of myocardial fibrosis was significantly lower, and the capillary vascular density was significantly higher in the recovery group than in the non-recovery group [16% (standard deviation 5.9%) vs 28% (5.9%), P?=?0.021, and 65 (11) vs 43 (18) units/high-power field, P?=?0.037, respectively]. The changes during 3?months after BHE implantation in LV diastolic dimension (z-score) and ejection fraction were significantly greater in the recovery group than in the non-recovery group [-9.6 (3.5) vs -3.6 (4.5), P?=?0.045, and 36% (13%) vs 13% (13%), P?=?0.032, respectively].
CONCLUSIONS:
In paediatric patients <10?kg with dilated cardiomyopathy, bridge to recovery with BHE implantation was achieved in patients with less injured LV myocardial histology at BHE implantation.
© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
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The Impact of Patient Sex on the Response to Intramyocardial Mesenchymal Stem Cell Administration in Patients with Non-Ischemic Dilated Cardiomyopathy.
Cardiovasc Res2020 Feb;():. doi: cvaa004.
Florea Victoria, Rieger Angela C, Natsumeda Makoto, Tompkins Bryon A, Banerjee Monisha N, Schulman Ivonne H, Premer Courtney, Khan Aisha, Valasaki Krystalenia, Mantero Alejandro, Balkan Wayne, Mitrani Raul D, Hare Joshua M,
Abstract
AIMS:
Sex differences impact the occurrence, presentation, prognosis, and response to therapy in heart disease. Particularly, the phenotypic presentation of patients with non-ischemic dilated cardiomyopathy (NIDCM) differs between men and women. However, whether the response to mesenchymal stem cell (MSC) therapy is influenced by sex remains unknown. We hypothesize that males and females with NIDCM respond similarly to MSC therapy.
METHODS AND RESULTS:
Male (n?=?24) and female (n?=?10) patients from the POSEIDON-DCM trial who received MSCs via transendocardial injections were evaluated over 12 months. Endothelial function was measured at baseline and 3 months post-TESI. At baseline, EF was lower (p?=?0.004) and end diastolic volume (EDV; p?=?0.0002) and end systolic volume (ESV; p?=?0.0002) were higher in males vs. females. In contrast, baseline demographic characteristics, Minnesota Living with Heart Failure Questionnaire (MLHFQ), and 6-minute walk test (6MWT) were similar between groups. EF improved in males by 6.2 units (p?=?0.04) and in females by 8.6 units (p?=?0.04; males vs. females, p?=?0.57). EDV and ESV were unchanged over time. The MLHFQ score, New York Heart Association (NYHA) class, endothelial progenitor cell-colony forming units (EPC-CFUs), and serum TNF-? improved similarly in both groups.
CONCLUSIONS:
Despite major differences in phenotypic presentation of NIDCM in males and females, this study is the first of its kind to demonstrate that MSC therapy improves a variety of parameters in NIDCM irrespective of patient sex. These findings have important clinical and pathophysiologic implications regarding the impact of sex on responses to cell-based therapy for NIDCM.
TRANSLATIONAL PERSPECTIVE:
Important patient sex differences exist in NIDCM clinical phenotype and gene expression profiles. The effectiveness of pharmacological treatment relative to patient sex requires evaluation due to the paucity of sex-specific data in clinical trials. Herein, we report that despite baseline phenotypic differences in left ventricular remodeling, MSC treatment improves the NIDCM phenotype irrespective of patient sex. Importantly, MSC administration to female patients may lead to an increased rate of heart failure with recovered EF, which carries an improved mortality, transplant rate, and hospitalization rate. This hypothesis-generating study encourages the design of future trials that evaluate patient sex differences in response to cell-based therapy.
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions please email: journals.permissions@oup.com.
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Reversible Mitochondrial Fragmentation in iPSC-Derived Cardiomyocytes From Children With DCMA, a Mitochondrial Cardiomyopathy.
Can J Cardiol2019 Oct;():. doi: S0828-282X(19)31286-3.
Rohani Leili, Machiraju Pranav, Sabouny Rasha, Meng Guoliang, Liu Shiying, Zhao Tian, Iqbal Fatima, Wang Xuemei, Ravandi Amir, Wu Joseph C, Khan Aneal, Shutt Timothy, Rancourt Derrick, Greenway Steven C,
Abstract
BACKGROUND:
Dilated cardiomyopathy with ataxia syndrome (DCMA) is an understudied autosomal recessive disease caused by loss-of-function mutations in the poorly characterized gene DNAJC19. Clinically, DCMA is commonly associated with heart failure and early death in affected children through an unknown mechanism. DCMA has been linked to Barth syndrome, a rare but well-studied disorder caused by deficient maturation of cardiolipin (CL), a key mitochondrial membrane phospholipid.
METHODS:
Peripheral blood mononuclear cells from 2 children with DCMA and severe cardiac dysfunction were reprogrammed into induced pluripotent stem cells (iPSCs). Patient and control iPSCs were differentiated into beating cardiomyocytes (iPSC-CMs) using a metabolic selection strategy. Mitochondrial structure and CL content before and after incubation with the mitochondrially targeted peptide SS-31 were quantified.
RESULTS:
Patient iPSCs carry the causative DNAJC19 mutation (rs137854888) found in the Hutterite population, and the iPSC-CMs demonstrated highly fragmented and abnormally shaped mitochondria associated with an imbalanced isoform ratio of the mitochondrial protein OPA1, an important regulator of mitochondrial fusion. These abnormalities were reversible by incubation with SS-31 for 24 hours. Differentiation of iPSCs into iPSC-CMs increased the number of CL species observed, but consistent, significant differences in CL content were not seen between patients and control.
CONCLUSIONS:
We describe a unique and novel cellular model that provides insight into the mitochondrial abnormalities present in DCMA and identifies SS-31 as a potential therapeutic for this devastating disease.
Copyright © 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
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Secreted Phospholipase A-IIA Modulates Transdifferentiation of Cardiac Fibroblast through EGFR Transactivation: An Inflammation-Fibrosis Link.
Cells2020 Feb;9(2):. doi: E396.
Martin Ruben, Gutierrez Beatriz, Cordova Claudia, Roman Alberto San, Alvarez Yolanda, Hernandez Marita, Cachofeiro Victoria, Nieto Maria L,
Abstract
Secreted phospholipase A-IIA (sPLA-IIA) is a pro-inflammatory protein associated with cardiovascular disorders, whose functions and underlying mechanisms in cardiac remodelling are still under investigation. We herein study the role of sPLA-IIA in cardiac fibroblast (CFs)-to-myofibroblast differentiation and fibrosis, two major features involved in cardiac remodelling, and also explore potential mechanisms involved. In a mice model of dilated cardiomyopathy (DCM) after autoimmune myocarditis, serum and cardiac sPLA-IIA protein expression were found to be increased, together with elevated cardiac levels of the cross-linking enzyme lysyl oxidase (LOX) and reactive oxygen species (ROS) accumulation. Exogenous sPLA-IIA treatment induced proliferation and differentiation of adult rat CFs. Molecular studies demonstrated that sPLA-IIA promoted Src phosphorylation, shedding of the membrane-anchored heparin-binding EGF-like growth factor (HB-EGF) ectodomain and EGFR phosphorylation, which triggered phosphorylation of ERK, P70S6K and rS6. This was also accompanied by an up-regulated expression of the bone morphogenic protein (BMP)-1, LOX and collagen I. ROS accumulation were also found to be increased in sPLA-IIA-treated CFs. The presence of inhibitors of the Src/ADAMs-dependent HB-EGF shedding/EGFR pathway abolished the CF phenotype induced by sPLA-IIA. In conclusion, sPLA-IIA may promote myofibroblast differentiation through its ability to modulate EGFR transactivation and signalling as key mechanisms that underlie its biological and pro-fibrotic effects.
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Echocardiographic parameters, speckle tracking, and brain natriuretic peptide levels as indicators of progression of indeterminate stage to Chagas Cardiomyopathy.
Echocardiography2020 Feb;():. doi: 10.1111/echo.14603.
Echeverría Luis E, Rojas Lyda Z, Villamizar María C, Luengas Carlos, Chaves Angel M, Rodríguez Jaime A, Campo Rafael, Clavijo Claudia, Redondo Adriana M, López Luis A, Gómez-Ochoa Sergio Alejandro, Morillo Carlos A, Rueda-Ochoa Oscar L, Franco Oscar H,
Abstract
BACKGROUND:
Chronic Chagas cardiomyopathy (CCM) is characterized by a unique type of cardiac involvement. Few studies have characterized echocardiographic (Echo) transitions from the indeterminate Chagas disease (ChD) form to CCM. The objective of this study was to identify the best cutoffs in multiple Echo parameters, speckle tracking, and N-terminal pro B-type natriuretic peptide (NT-proBNP) to distinguish patients without CCM (stage A) vs patients with myocardial involvement (stages B, C, or D).
METHODS:
Cross-sectional study conducted in 273 consecutive patients with different CCM stages. Echo parameters, NT-proBNP, and other clinical variables were measured. Logistic regression models (dichotomized in stage A versus B, C, and D) adjusted for age, sex, body mass index, and NT-proBNP were performed.
RESULTS:
Left ventricular global longitudinal strain (LV-GLS), mitral flow E velocity, LV mass index, and NT-proBNP identified early changes that differentiated stages A vs B, C, and D. The LV-GLS with a cutoff -20.5% showed the highest performance (AUC 92.99%; accuracy 84.56% and negative predictive value (NPV) 88.82%), which improved when it was additionally adjusted by NT-proBNP with a cutoff -20.0% (AUC 94.30%; accuracy 88.42% and NPV 93.55%).
CONCLUSIONS:
Our findings suggest that Echo parameters and NT-proBNP may be used as diagnostic variables in detecting the onset of myocardial alterations in patients with the indeterminate stage of ChD. LV-GLS was the more accurate measurement regarding stage A differentiation from the stages B, C, and D. Prospective longitudinal studies are needed to validate these findings.
© 2020 Wiley Periodicals, Inc.
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Epicardial ablation of ventricular tachycardia using a new high-density mapping system.
Rev Port Cardiol2020 Feb;():. doi: S0870-2551(17)30864-8.
Cavaco Diogo, Carmo Pedro, Mesquita João, Scanavacca Maurício, Adragão Pedro,
Abstract
We report the case of a 44-year-old woman who was referred for ablation of recurrent ventricular tachycardia (VT) in the setting of dilated cardiomyopathy secondary to myocarditis. The ECG displayed a right bundle branch block morphology and superior axis in the frontal plane, associated with a pseudo delta wave in the precordial leads that suggested an epicardial origin. Cardiac magnetic resonance performed prior to the procedure showed late gadolinium enhancement at the lateral wall of the left ventricle (LV) and excluded subendocardial fibrosis in either ventricle. This information was crucial and influenced the ablation strategy, identifying the target area as exclusively epicardial, thus avoiding unnecessary mapping of the endocardial surface of the LV. Epicardial activation mapping and ablation during VT were performed using the Orion® high-density catheter (Boston Scientific Inc.) and the Rhythmia® mapping system (Boston Scientific Inc.). Applications near the exit site immediately terminated the tachycardia, which was no longer inducible. One year after the procedure the patient was still in sinus rhythm with no episodes of VT or non-sustained VT recorded by continuous monitoring via an implanted cardioverter-defibrillator.
Copyright © 2019 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.
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Vacuolated cardiomyocytes in human endomyocardial biopsy specimens.
J Cardiol Cases2020 Feb;21(2):54-58. doi: 10.1016/j.jccase.2019.09.012.
Takemura Genzou, Onoue Kenji, Arimoto Takanori, Watanabe Tetsu, Tsujimoto Akiko, Takada Chihiro, Okada Hideshi, Nakano Tomoya, Sakaguchi Yasuhiro, Miyazaki Nagisa, Watanabe Takatomo, Kanamori Hiromitsu, Ogura Shinji, Saito Yoshihiko, Fujiwara Takako, Fujiwara Hisayoshi, Hotta Yasuaki,
Abstract
We encountered an unfamiliar finding during electron microscopic examination of an endomyocardial biopsy obtained from a 55-year-old woman suffering from heart failure due to dilated phase hypertrophic cardiomyopathy. Many cardiomyocytes contained large vacuoles that were mainly empty except for small amounts of amorphous substrate. These were not autophagic vacuoles, as they lacked limiting membranes. Six years later, we encountered similar histological findings in three successive biopsies sourced from another hospital. They were obtained from a 77-year-old man with hypertrophic cardiomyopathy, a 28-year-old woman with endocardial fibrosis, and a 33-year-old man with dilated cardiomyopathy. This biopsy was the second for the endocardial fibrosis patient, and her first biopsy showed no vacuoles within cardiomyocytes. Close inspection of the procedures revealed that in all of these cases the fixed biopsy specimens were carried to the hospital from other institutes using a refrigerated courier service. We then fixed rat heart tissues, froze them once, and processed them for electron microscopy. In that experiment, we were able to reproduce the vacuolar cardiomyocytes, thereby demonstrating it to be a laboratory artifact. We therefore want to emphasize to physicians not to freeze biopsy specimens and not to use a refrigerated courier service for their transport. < Under an electron microscope, large vacuoles were observed within many cardiomyocytes in endomyocardial biopsies obtained from 4 patients with cardiomyopathies of different etiologies, which were not autophagic vacuoles. Since an animal experiment could reproduce a similar histological finding by freezing the tissue after fixation, such an unfamiliar finding was considered to be a laboratory artifact. We would call physicians' attention not to freeze the biopsy specimens even after fixation.>.
© 2019 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
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Genetic Basis and Genotype-Phenotype Correlations in Han Chinese Patients with Idiopathic Dilated Cardiomyopathy.
Sci Rep2020 Feb;10(1):2226. doi: 10.1038/s41598-020-58984-7.
Zhang Xin-Lin, Xie Jun, Lan Rong-Fang, Kang Li-Na, Wang Lian, Xu Wei, Xu Biao,
Abstract
Dilated cardiomyopathy (DCM) is one of the leading causes of heart failure. A large proportion of genetic cause remains unexplained, especially in idiopathic DCM. We performed target next-generation sequencing of 102 genes which were known causes or candidate genes for cardiomyopathies and channelpathies in 118 prospectively recruited Han Chinese patients with idiopathic DCM. 41 of the 118 patients carried 40 pathogenic or likely pathogenic variants, providing a molecular diagnosis in 34.7% of patients. 32 of these variants were novel. TTN truncating variants were predominant, with a frequency of 31.0%, followed by variants of LMNA (14.3%), RBM20 (4.8%), and NEXN (4.8%). These 4 genes accounted for over half variants identified. No significant difference in clinical characteristics or rates of reaching the composite end point (cardiac transplantation and death from cardiac causes) between pathogenic or likely pathogenic variant carriers and noncarriers (hazard ratio 1.11, 95% CI: 0.41 to 3.00), or between patients with TTN truncating variants or without (hazard ratio 0.49, 95% CI: 0.36 to 6.10). In our prospective study, we first determined the overall genetic profiles and genotype-phenotype correlations in Han Chinese idiopathic DCM patients, which could provide insight for genetic diagnosis of DCM in this population.
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First reported case of lead-related infective endocarditis secondary to Capnocytophaga canimorsus: 'Dog Scratch' endocarditis.
BMJ Case Rep2020 Feb;13(2):. doi: e233783.
Squire Gareth, Hetherington Simon,
Abstract
A 76-year-old woman presented with a 6-week history of malaise, night sweats and recurrent fever. She had a background of dilated cardiomyopathy for which she had a cardiac resynchronisation device in situ. She had several hospital admissions across this time with differing diagnoses offered. She received multiple courses of antibiotics with short-term symptom resolution. Blood cultures grew Gram-negative rods and samples were sent to a specialist centre for subtype analysis. A transthoracic echocardiogram revealed thickening of the distal right ventricular lead. A transoesophageal echocardiogram demonstrated a clearer vegetation on this lead. It transpired that she had been scratched by her dog a fortnight before symptom onset. The causal bacterium was reported as , a bacterium that exists almost exclusively in the saliva and claws of dogs and cats. She received an extended course of antibiotics with eventual removal of the infected device.
© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.
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Familial Dilated Cardiomyopathy Associated With a Novel Combination of Compound Heterozygous Variants.
Front Physiol2019 ;10():1612. doi: 10.3389/fphys.2019.01612.
Landim-Vieira Maicon, Johnston Jamie R, Ji Weizhen, Mis Emily K, Tijerino Joshua, Spencer-Manzon Michele, Jeffries Lauren, Hall E Kevin, Panisello-Manterola David, Khokha Mustafa K, Deniz Engin, Chase P Bryant, Lakhani Saquib A, Pinto Jose Renato,
Abstract
Familial dilated cardiomyopathy (DCM), clinically characterized by enlargement and dysfunction of one or both ventricles of the heart, can be caused by variants in sarcomeric genes including (encoding cardiac troponin C, cTnC). Here, we report the case of two siblings with severe, early onset DCM who were found to have compound heterozygous variants in : p.Asp145Glu (D145E) and p.Asp132Asn (D132N), which were inherited from the parents. We began our investigation with CRISPR/Cas9 knockout of in , which resulted in a cardiac phenotype in tadpoles consistent with DCM. Despite multiple maneuvers, we were unable to rescue the tadpole hearts with either human cTnC wild-type or patient variants to investigate the cardiomyopathy phenotype . We therefore utilized porcine permeabilized cardiac muscle preparations (CMPs) reconstituted with either wild-type or patient variant forms of cTnC to examine effects of the patient variants on contractile function. Incorporation of 50% WT/50% D145E into CMPs increased Ca sensitivity of isometric force, consistent with prior studies. In contrast, incorporation of 50% WT/50% D132N, which had not been previously reported, decreased Ca sensitivity of isometric force. CMPs reconstituted 50-50% with both variants mirrored WT in regard to myofilament Ca responsiveness. Sinusoidal stiffness (SS) (0.2% peak-to-peak) and the kinetics of tension redevelopment () at saturating Ca were similar to WT for all preparations. Modeling of Ca-dependence of support the observation from Ca responsiveness of steady-state isometric force, that the effects on each mutant (50% WT/50% mutant) were greater than the combination of the two mutants (50% D132N/50% D145E). Further studies are needed to ascertain the mechanism(s) of these variants.
Copyright © 2020 Landim-Vieira, Johnston, Ji, Mis, Tijerino, Spencer-Manzon, Jeffries, Hall, Panisello-Manterola, Khokha, Deniz, Chase, Lakhani and Pinto.
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Serial evaluation of cardiac biomarker NT-proBNP with speckle tracking echocardiography in a 6-year-old Golden Retriever dog with subaortic stenosis and dilated cardiomyopathy.
Vet Q2020 Feb;():1-10. doi: 10.1080/01652176.2020.1727992.
Ro Woong-Bin, Kang Min-Hee, Park Hee-Myung,
Abstract
A 6-year-old 37.5-kg Golden Retriever dog was presented with intermittent coughing and cardiac murmur. The dog was diagnosed with subaortic stenosis (SAS) and dilated cardiomyopathy (DCM). The serum N-terminal pro B-type natriuretic peptide (NT-proBNP) concentration, conventional echocardiography, and two-dimensional speckle tracking echocardiography (2D-STE) were serially evaluated for 6 months. At admission, the dog showed a significant increase in the serum NT-proBNP concentration and severe reduction in the 2D-STE strain values. During the monitoring period, the 2D-STE was capable of detecting segmental dyskinesia in apical region, even though the concentration of NT-proBNP in serum was decreased. In addition, longitudinal deformations most sensitively indicated the myocardial damage, while radial and circumferential deformations accurately indicated myocardial contractility. This is the first case report of a dog with SAS and DCM, which demonstrated and compared serial changes of NT-proBNP and 2D-STE with disease progression. In this case, the combined use of NT-proBNP with 2D-STE showed excellent diagnostic and prognostic utility in investigating myocardial injury.
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Truncating titin variants in dilated cardiomyopathy: not only LVEF recovery, but also maintenance.
Rev Esp Cardiol (Engl Ed)2020 Feb;():. doi: S1885-5857(20)30002-5.
Valverde-Gómez María, Salguero-Bodes Rafael, Martín-Arriscado Cristina, Delgado-Jiménez Juan, Arribas-Ynsaurriaga Fernando, Palomino-Doza Julián,
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Right Ventricular Assist Devices After Heart Transplantation.
Transplant Proc2020 Feb;():. doi: S0041-1345(19)31133-9.
Escalona-Rodriguez Sara, Palomo-López Nora, Escoresca-Ortega Ana, Adsuar-Gómez Alejandro, Porras-López Manuel, Corcia-Palomo Yael, Martin-Bermudez Rafael, Martín-Villén Luis,
Abstract
BACKGROUND:
Severe right ventricular failure (RVF) has a significant incidence among cardiac transplant patients. It is a serious complication and an independent risk factor for postoperative mortality. In this setting, ventricular assist devices (VADs) must be considered if conservative medical management fails. This study sought to examine our series of patients with early RVF after heart transplantation requiring VAD support.
METHOD:
We analyzed consecutive, adult heart transplant recipients at a third level intensive care unit who underwent transplantation from January 2011 to March 2019 requiring post-transplant mechanical circulatory support for RVF. Demographic characteristics, clinical data, complications, and survival rates were collected.
RESULTS:
Ten patients were included. Median age was 50 years (range, 31.7-57). Eight patients (80%) were male. The most frequent indication for heart transplantation was ischemic heart disease (4 patients) followed by dilated cardiomyopathy and congenital heart disease (2 patients). Preoperative pulmonary hypertension was present in 6 patients. Three patients required a VAD before transplant. Whole survival rate was 60%. After heart transplantation, 7 patients required renal replacement therapy, 2 patients suffered a hemorrhagic stroke, and 5 patients needed a tracheostomy for long-term ventilation.
CONCLUSION:
Patients who develop RVF after transplantation have an increased incidence of complications and high mortality after surgery. VADs could be implanted immediately after heart transplantation in high-risk patients.
Copyright © 2020 Elsevier Inc. All rights reserved.
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Peripheral microRNA panels to guide the diagnosis of familial cardiomyopathy.
Transl Res2020 Jan;():. doi: S1931-5244(20)30003-7.
Belmonte Thalía, Mangas Alipio, Calderon-Dominguez Maria, Quezada-Feijoo Maribel, Ramos Monica, Campuzano Oscar, Gomez Silvia, Peña Maria Luisa, Cubillos-Arango Andres M, Dominguez Fernando, Llorente-Cortés Vicenta, de Gonzalo-Calvo David, Toro Rocio,
Abstract
Etiology-based diagnosis of dilated cardiomyopathy (DCM) is challenging. We evaluated whether peripheral microRNAs (miRNAs) could be used to characterize the DCM etiology. We investigated the miRNA plasma profiles of 254 subjects that comprised 5 groups: Healthy subjects (n?=?70), idiopathic DCM patients (n?=?55), ischemic DCM patients (n?=?60) and 2 groups of patients with pathogenic variants responsible for familial DCM in the LMNA (LMNA, n?=?37) and BAG3 (BAG3, n?=?32) genes. Diagnostic performance was assessed using receiver operating characteristic curves. In a screening study (n?=?30), 179 miRNAs robustly detected in plasma samples were profiled in idiopathic DCM and carriers of pathogenic variants. After filtering, 26 miRNA candidates were selected for subsequent quantification in the whole study population. In the validation study, a 6-miRNA panel identified familial DCM with an AUC (95% confidence interval [CI]) of 87.8 (82.0-93.6). The 6-miRNA panel also distinguished between specific DCM etiologies with AUCs ranging from 85.9 to 89.9. Only 1 to 10 of the subjects in the first and second tertiles of the 6-miRNA panel were patients with familial DCM. Additionally, a 5-miRNA panel showed an AUC (95% CI) of 87.5 (80.4-94.6) for the identification of carriers with pathogenic variants who were phenotypically negative for DCM. The 5-miRNA panel discriminated between carriers and healthy controls with AUCs ranging from 83.2 to 90.8. Again, only 1 to 10 of the subjects in the lowest tertiles of the 5-miRNA panel were carriers of pathogenic variants. In conclusion, miRNA signatures could be used to rule out patients with pathogenic variants responsible for DCM.
Copyright © 2020 Elsevier Inc. All rights reserved.
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Early experience of Sacubitril-Valsartan in heart failure with reduced ejection fraction in real-world clinical setting.
ESC Heart Fail2020 Feb;():. doi: 10.1002/ehf2.12644.
Nordberg Backelin Charlotte, Fu Michael, Ljungman Charlotta,
Abstract
AIMS:
Sacubitril/Valsartan (Sac/Val) was proven more effective than enalapril for symptomatic patients with heart failure (HF) with reduced ejection fraction (HFrEF). This study aimed to investigate eligibility, titration, and tolerability for Sac/Val in a real-world clinical setting.
METHODS AND RESULTS:
This retrospective cohort study consists of two parts. In Part 1 (eligibility study), all patients discharged from Sahlgrenska University Hospital due to HF were consecutively included during 1 year. Data from the patients' medical records were collected. Patients were adjudicated to be eligible based on European Society of Cardiology (ESC) criteria for angiotensin receptor neprilysin inhibitor (ARNI) with the exception of N-terminal (NT)-proBNP levels. Patients who received <50% of target dose angiotensin-converting enzyme/angiotensin receptor blocker and otherwise fulfilled ESC criteria were adjudicated to be potentially eligible. In Part 2 (tolerability study), all patients receiving Sac/Val during the same period were included. Medical data regarding dose, titration, and adverse effects and events were registered. A total of 1355 patients (mean age 78 ± 13 years) were hospitalized for HF and 619 patients had an EF ?40%. Twenty percent were eligible for initiation of ARNI, and additionally 8% were potentially eligible. In all 95 patients (mean age 65 ± 12 years) were initiated with Sac/Val, which correlates to 13%. The patients who were initiated were younger (65 years), more often had dilated cardiomyopathy (31%), more often were on guideline-directed medical therapy, and had a higher frequency of cardiac resynchronization therapy and implantable cardioverter-defibrillator compared with the patients who did not receive Sac/Val. Of the initiated patients, 59% reached target dose of Sac/Val, and 15% discontinued due to adverse effects. The most common cause of discontinuation was benign gastrointestinal adverse effects, followed by elevated creatinine, malaise, and vertigo. Female gender [odds ratio (OR) 3.58; 95% CI 1.07-2.00; P = 0.038] and NT-proBNP ? median level (OR 0.48; 95% CI 0.26-0.90; P = 0.021) was associated with termination of the medication.
CONCLUSIONS:
Among HFrEF patients in this real-world cohort, 20% were eligible for ARNI; however, only 13% received the treatment. Sac/Val was well tolerated, but 41% of the patients did not reach target dose. How this affects outcome is not known and needs further investigation.
© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.
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