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Biomolecules Jun 2024Dilated cardiomyopathy (DCM) is a common cause of heart failure (HF) and heart transplantation (HTx), with genetic factors playing a significant role. In recent years,... (Review)
Review
Dilated cardiomyopathy (DCM) is a common cause of heart failure (HF) and heart transplantation (HTx), with genetic factors playing a significant role. In recent years, the RNA-binding protein motif 20 (), which affects the gene splicing of various proteins with different cellular functions, was identified as the first DCM gene with regulatory properties. Variants of have been associated with severe forms of DCM. The aim of this critical systematic review was to analyse cardiomyopathy clinical features and outcomes. According to PRISMA guidelines, a search was run in the PubMed, Scopus and Web of Science electronic databases using the following keywords: ""; "cardiomyopathy"; "arrhythmias"; "heart failure". A total of 181 records were screened, of which 27 studies were potentially relevant to the topic. Through the application of inclusion and exclusion criteria, eight papers reporting 398 patients with pathogenic variants were analysed. The mean age at presentation was 41 years. Familiarity with cardiomyopathy was available in 59% of cases, with 55% of probands reporting a positive family history. Imaging data indicated a mild reduction of left ventricular ejection fraction (mean LVEF 40%), while tissue characterization was reported in 24.3% of cases, showing late gadolinium enhancement in 33% of patients. Composite outcomes of sustained monomorphic ventricular tachycardia or ventricular fibrillation occurred in 19.4% of patients, with 12% undergoing HTx. There were no gender differences in arrhythmic outcomes, while 96.4% of patients who underwent HTx were male. In conclusion, cardiomyopathy exhibits a severe phenotypic expression, both in terms of arrhythmic burden and HF progression.
Topics: Humans; RNA-Binding Proteins; Cardiomyopathy, Dilated; Male; Female; Adult
PubMed: 38927106
DOI: 10.3390/biom14060702 -
International Journal of Molecular... May 2024Inherited muscular diseases (MDs) are genetic degenerative disorders typically caused by mutations in a single gene that affect striated muscle and result in progressive... (Review)
Review
Inherited muscular diseases (MDs) are genetic degenerative disorders typically caused by mutations in a single gene that affect striated muscle and result in progressive weakness and wasting in affected individuals. Cardiac muscle can also be involved with some variability that depends on the genetic basis of the MD (Muscular Dystrophy) phenotype. Heart involvement can manifest with two main clinical pictures: left ventricular systolic dysfunction with evolution towards dilated cardiomyopathy and refractory heart failure, or the presence of conduction system defects and serious life-threatening ventricular arrhythmias. The two pictures can coexist. In these cases, heart transplantation (HTx) is considered the most appropriate option in patients who are not responders to the optimized standard therapeutic protocols. However, cardiac transplant is still considered a relative contraindication in patients with inherited muscle disorders and end-stage cardiomyopathies. High operative risk related to muscle impairment and potential graft involvement secondary to the underlying myopathy have been the two main reasons implicated in the generalized reluctance to consider cardiac transplant as a viable option. We report an overview of cardiac involvement in MDs and its possible association with the underlying molecular defect, as well as a systematic review of HTx outcomes in patients with MD-related end-stage dilated cardiomyopathy, published so far in the literature.
Topics: Humans; Cardiomyopathy, Dilated; Heart Transplantation; Muscular Dystrophies
PubMed: 38791328
DOI: 10.3390/ijms25105289 -
International Journal of Cardiology.... Apr 2024Cardiac magnetic resonance imaging (CMR) based T1 mapping and extracellular volume fraction (ECV) are powerful tools for identifying myocardial fibrosis. This systematic...
BACKGROUND
Cardiac magnetic resonance imaging (CMR) based T1 mapping and extracellular volume fraction (ECV) are powerful tools for identifying myocardial fibrosis. This systematic review and -analysis aims to characterize the utility of native T1 mapping and ECV in patients with non-ischemic cardiomyopathy (NICM) and to clarify the prognostic significance of elevated values.
METHODS
A literature search was conducted for studies reporting on use of CMR-based native T1 mapping and ECV measurement in NICM patients and their association with major adverse cardiac events (MACE), ventricular arrhythmias (VAs), and left ventricular reverse remodeling (LVRR). Databases searched included: Ovid MEDLINE, EMBASE, Web of Science, and Google Scholar. The search was not restricted to time or publication status.
RESULTS
Native T1 and ECV were significantly higher in NICM patients compared to controls (MD 78.80, 95 % CI 50.00, 107.59; p < 0.01; MD 5.86, 95 % CI 4.55, 7.16; p < 0.01). NICM patients who experienced MACE had higher native T1 and ECV (MD 52.87, 95 % CI 26.59, 79.15; p < 0.01; MD 6.03, 95 % CI 3.79, 8.26; p < 0.01). There was a non-statistically significant trend toward higher native T1 time in NICM patients who experienced VAs. NICM patients who were poor treatment responders had higher baseline native T1 and ECV (MD 40.58, 95 % CI 12.90, 68.25; p < 0.01; MD 3.29, 95 % CI 2.25, 4.33; p < 0.01).
CONCLUSIONS
CMR-based native T1 and ECV quantification may be useful tools for risk stratification of patients with NICM. They may provide additional diagnostic utility in combination with LGE, which poorly characterizes fibrosis in patients with diffuse myocardial involvement.
PubMed: 38371310
DOI: 10.1016/j.ijcha.2024.101339 -
European Journal of Medical Genetics Apr 2024T-Box Transcription Factor 5 (TBX5) variants are associated with Holt-Oram syndrome. Holt-Oram syndrome display phenotypic variability, regarding upper limb defects,... (Review)
Review
T-Box Transcription Factor 5 (TBX5) variants are associated with Holt-Oram syndrome. Holt-Oram syndrome display phenotypic variability, regarding upper limb defects, congenital heart defects, and arrhythmias. To investigate the genotype-phenotype relationship between TBX5 variants and cardiac disease, we performed a systematic review of the literature. Through the systematic review we identified 108 variants in TBX5 associated with a cardiac phenotype in 277 patients. Arrhythmias were more frequent in patients with a missense variant (48% vs 30%, p = 0.009) and upper limb abnormalities were more frequent in patients with protein-truncating variants (85% vs 64%, p = 0.0008). We found clustering of missense variants in the T-box domain. Furthermore, we present a family with atrial septal defects. By whole exome sequencing, we identified a novel missense variant p.Phe232Leu in TBX5. The cardiac phenotype included atrial septal defect, arrhythmias, heart failure, and dilated cardiomyopathy. Clinical examination revealed subtle upper limb abnormalities. Thus, the family corresponds to the diagnostic criteria of Holt-Oram syndrome. We provide an overview of cardiac phenotypes associated with TBX5 variants and show an increased risk of arrhythmias associated to missense variants compared to protein-truncating variants. We report a novel missense variant in TBX5 in a family with an atypical Holt-Oram syndrome phenotype.
Topics: Humans; Abnormalities, Multiple; Heart Defects, Congenital; Heart Septal Defects, Atrial; Lower Extremity Deformities, Congenital; Phenotype; T-Box Domain Proteins; Upper Extremity Deformities, Congenital
PubMed: 38336121
DOI: 10.1016/j.ejmg.2024.104920 -
Veterinary Sciences Jan 2024Different risk factors for atrial fibrillation (AF) development have been identified in numerous studies on humans, but this information is less clearly available on the... (Review)
Review
Different risk factors for atrial fibrillation (AF) development have been identified in numerous studies on humans, but this information is less clearly available on the dog. The aim of this systematic review is to determine the risk factors for AF in the dog. Following the PRISMA 2020 guidelines, we conducted a comprehensive search using the Web of Science and Scopus databases for articles reporting on cases of spontaneously occurring AF in dogs. The level of evidence was assessed using the Evidence Quality Grading System of the National Institute of Health. One thousand forty-three studies were initially identified, and twenty of them were included in this systematic review involving 2,359,275 dogs, of which 4807 showed spontaneously occurring AF. Genetics, for the Irish Wolfhound, increased body weight, and left atrial enlargement were the main risk factors for the development of AF in dogs with different cardiac diseases, particularly myxomatous mitral valve disease (MMVD) and dilated cardiomyopathy (DCM). However, some differences were found between these two cardiac diseases regarding additional risk factors. In particular, the presence of congestive heart failure and echocardiographic evidence of increased left atrial pressure or the presence of right atrial enlargement emerged as risk factors in dogs with MMVD or DCM, respectively. Furthermore, significant differences in risk factors were observed between dogs and humans. In particular, advanced age and male sex are not reliable indicators of an increased risk of AF in dogs.
PubMed: 38275929
DOI: 10.3390/vetsci11010047 -
Frontiers in Bioscience (Landmark... Dec 2023Plasma renin activity (PRA) has gained relevance as prognostic marker in adults with heart failure. The use of PRA as a clinically meaningful parameter in children and...
BACKGROUND
Plasma renin activity (PRA) has gained relevance as prognostic marker in adults with heart failure. The use of PRA as a clinically meaningful parameter in children and children with heart failure requires a thorough knowledge of the factors that influence PRA to correctly assess PRA levels. We aim to evaluate the influence of age, heart failure and angiotensin-converting enzyme inhibitor (ACEi) on PRA levels in children.
METHODS
We conducted a systematic literature search to identify studies on PRA levels in healthy children and in children with heart failure. In addition, we analysed PRA data measured before (n = 35, aged 25 days-2.1 years), 4 hours after (n = 34) and within the first 8 days of enalapril treatment (n = 29) in children with heart failure from the European project Labeling of Enalapril from Neonates up to Adolescents (LENA).
RESULTS
Age has a profound effect on PRA levels in healthy children, as PRA levels in the literature are up to about 7 times higher in neonates than in older children. Children with heart failure younger than 6 months showed 3-4 times higher PRA levels than healthy peers in both the literature and the LENA studies. In the LENA studies, the ACEi enalapril significantly increased median predose PRA by a factor of 4.5 in children with heart failure after 4.7 ± 1.6 days of treatment (n = 29, < 0.01). Prior to treatment with enalapril, LENA subjects with symptomatic heart failure (Ross score ≥3) had a significantly higher PRA than LENA subjects with asymptomatic heart failure of comparable age (Ross score ≤2, < 0.05).
CONCLUSIONS
Age, heart failure and ACEi treatment have a notable influence on PRA and must be considered when assessing PRA as a clinically meaningful parameter.
CLINICAL TRIAL REGISTRATION
The trials are registered on the EU Clinical Trials Register (https://www.clinicaltrialsregister.eu).
TRIAL REGISTRATION NUMBERS
EudraCT 2015-002335-17, EudraCT 2015-002396-18.
Topics: Humans; Infant, Newborn; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Heart Failure; Renin; Renin-Angiotensin System; Infant; Child, Preschool
PubMed: 38179766
DOI: 10.31083/j.fbl2812335 -
International Journal of Medical... 2023The members of the transmembrane emp24 domain-containing protein (TMED) family are summarized in human as four subfamilies, α (TMED 4, 9), β (TMED 2), γ (TMED1, 3, 5,... (Review)
Review
The members of the transmembrane emp24 domain-containing protein (TMED) family are summarized in human as four subfamilies, α (TMED 4, 9), β (TMED 2), γ (TMED1, 3, 5, 6, 7) and δ (TMED 10), with a total of nine members, which are important regulators of intracellular protein transport and are involved in normal embryonic development, as well as in the pathogenic processes of many human diseases. Here we systematically review the composition, structure and function of TMED family members, and describe the progress of TMED family in human diseases, including malignancies (head and neck tumors, lung cancer, breast cancer, ovarian cancer, endometrial cancer, gastrointestinal tumors, urological tumors, osteosarcomas, etc.), immune responses, diabetes, neurodegenerative diseases, and nonalcoholic fatty liver disease, dilated cardiomyopathy, mucin 1 nephropathy (MKD), and desiccation syndrome (SS). Finally, we discuss and prospect the potential of TMED for disease prognosis prediction and therapeutic targeting, with a view to laying the foundation for therapeutic research based on TMED family causative genes.
Topics: Pregnancy; Female; Humans; Membrane Proteins; Protein Transport; Non-alcoholic Fatty Liver Disease; Vesicular Transport Proteins
PubMed: 37928880
DOI: 10.7150/ijms.87272 -
Frontiers in Cardiovascular Medicine 2023Ivabradine improves cardiac function in patients with heart failure, but its effect on dilated cardiomyopathy (DCM) remains unclear. We performed a systematic review and... (Review)
Review
BACKGROUND
Ivabradine improves cardiac function in patients with heart failure, but its effect on dilated cardiomyopathy (DCM) remains unclear. We performed a systematic review and meta-analysis to study the efficacy and potential mechanisms of ivabradine's effect on cardiac function and prognosis in patients with DCM.
METHODS
We searched PubMed, Cochrane Library, Embase, Web of Science, and four registers through September 28, 2022. All controlled trials of ivabradine for the treatment of DCM with congestive heart failure were included. Articles were limited to English, with the full text and necessary data available. We performed random- or fixed effects meta-analyses for all included outcome measures and compared the effect sizes for outcomes in patients treated with and without ivabradine. The quality of the studies was assessed using the Cochrane risk-of-bias tool for randomized trials (RoB2.0).
FINDINGS
Five trials with 357 participants were included. The pooled risk ratio was 0.48 [95% confidence interval (CI) (0.18, 1.25)] for all-cause mortality and 0.38 [95% CI (0.12, 1.23)] for cardiac mortality. The pooled mean difference was -15.95 [95% CI (-19.97, -11.92)] for resting heart rate, 3.96 [95% CI (0.99, 6.93)] for systolic blood pressure, 2.93 [95% CI (2.09, 3.77)] for left ventricular ejection fraction, -5.90 [95% CI (-9.36, -2.44)] for left ventricular end-systolic diameter, -3.41 [95% CI (-5.24, -1.58)] for left ventricular end-diastolic diameter, -0.81 [95% CI (-1.00, -0.62)] for left ventricular end-systolic volume, -0.67 [95% CI (-0.86, -0.48)] for left ventricular end-diastolic volume, -11.01 [95% CI (-19.66, -2.35)] for Minnesota Living with Heart Failure score, and -0.52 [95% CI (-0.73, -0.31)] for New York Heart Association class.
INTERPRETATION
Ivabradine reduces heart rate and ventricular volume, and improves cardiac function in patients with DCM, but showed no significant effect on the prognosis of patients.
PubMed: 37915740
DOI: 10.3389/fcvm.2023.1149351 -
American Journal of Cardiovascular... 2023Despite high surgical risk among heart transplant (HTx) recipients, who develop aortic valve diseases (AVD), transcutaneous aortic valve replacement (TAVR) has been...
BACKGROUND
Despite high surgical risk among heart transplant (HTx) recipients, who develop aortic valve diseases (AVD), transcutaneous aortic valve replacement (TAVR) has been scarcely reported as a viable option in this patient population.
METHODS
A systematic review was conducted to identify studies reporting the outcomes of HTx recipients who developed AVD of the donor heart and underwent TAVR. Studies were eligible if they provided individual-level data for HTx recipients, who underwent TAVR on the donor heart. Review articles, editorials or commentaries, studies lacking original data, or those reporting surgical valve replacement for AVD in HTx recipients were excluded.
RESULTS
A total of 15 case reports, encompassing 15 patients, describing characteristics and outcomes of HTx recipients undergoing TAVR were included. These included 13 males and 2 females with an average age of 63.6±15 years. The indications for HTx were non-ischemic dilated cardiomyopathy, ischemic cardiomyopathy and ischemic dilated cardiomyopathy in 42.9%, 35.7%, and 21.4% of the patients, respectively. The main indication for aortic valve replacement (AVR) among HTx recipients was aortic stenosis (73.3%). The transcutaneous approach was preferred over surgical AVR due to high surgical risk in > 50% of the patients. Both pre-TAVR transvalvular pressure gradient and the peak aortic pressure gradient decreased after the TAVR. Paravalvular leak was minimal/none to mild in all the patients post-TAVR. Most patients had an uneventful post-TAVR recovery with no recurrence of the symptoms or echocardiographic finings at a median follow-up of 6 months.
CONCLUSIONS
TAVR seems to be a viable option for HTx recipients who develop donor aortic valve diseases. However, there is a paucity of knowledge on the long-term survivability of the replaced aortic valves and the clinical and echocardiographic outcomes of HTx recipients undergoing TAVR.
PubMed: 37736356
DOI: No ID Found -
Scientific Reports Aug 2023Risk stratification based mainly on the impairment of left ventricular ejection fraction has limited performance in patients with nonischemic dilated cardiomyopathy... (Meta-Analysis)
Meta-Analysis
Risk stratification based mainly on the impairment of left ventricular ejection fraction has limited performance in patients with nonischemic dilated cardiomyopathy (NIDCM). Evidence is rapidly growing for the impact of myocardial scar identified by late gadolinium enhancement (LGE) cardiac magnetic resonance imaging (CMR) on cardiovascular events. We aim to assess the prognostic value of LGE on long-term arrhythmic and mortality outcomes in patients with NIDCM. PubMed, Scopus, and Cochrane databases were searched from inception to January 21, 2022. Studies that included disease-specific subpopulations of NIDCM were excluded. Data were independently extracted and combined via random-effects meta-analysis using a generic inverse-variance strategy. Data from 60 studies comprising 15,217 patients were analyzed with a 3-year median follow-up. The presence of LGE was associated with major ventricular arrhythmic events (pooled OR: 3.99; 95% CI 3.08, 5.16), all-cause mortality (pooled OR: 2.14; 95% CI 1.81, 2.52), cardiovascular mortality (pooled OR 2.83; 95% CI 2.23, 3.60), and heart failure hospitalization (pooled OR: 2.53; 95% CI 1.78, 3.59). Real-world evidence suggests that the presence of LGE on CMR was a strong predictor of adverse long-term outcomes in patients with NIDCM. Scar assessment should be incorporated as a primary determinant in the patient selection criteria for primary prophylactic implantable cardioverter-defibrillator placement.
Topics: Humans; Cardiomyopathy, Dilated; Gadolinium; Cicatrix; Contrast Media; Stroke Volume; Ventricular Function, Left; Magnetic Resonance Imaging
PubMed: 37612359
DOI: 10.1038/s41598-023-41087-4