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Trends in Cardiovascular Medicine Jan 2023Rare variants in JPH2 have been associated with a range of cardiac disease, including hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmias, and... (Review)
Review
Rare variants in JPH2 have been associated with a range of cardiac disease, including hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmias, and sudden cardiac death (SCD); however, our understanding of how variants in JPH2 correspond to specific modes of inheritance and correlate clinical phenotypes has not been comprehensively explored. In this systematic review, we assess current case reports and series that describe patients with JPH2 variants and cardiac disease. We identified a total of 61 variant-positive individuals, approximately 80% of whom had some form of cardiac disease, including 47% HCM, 18% DCM, and 14% arrhythmia/SCD. In analyzing the 24 probands described in the studies, we found that autosomal recessive, loss-of-function variants are associated with severe, early onset DCM, while autosomal dominant missense variants are associated with a wider range of cardiac disease, including HCM, arrhythmia, SCD, and cardiac conduction disease.
Topics: Humans; Membrane Proteins; Heart; Cardiomyopathy, Hypertrophic; Cardiomyopathy, Dilated; Death, Sudden, Cardiac
PubMed: 34861382
DOI: 10.1016/j.tcm.2021.11.006 -
Echo Research and Practice Mar 2018Patients with non-ischaemic systolic heart failure (HF) and idiopathic dilated cardiomyopathy (DCM) are a heterogenous group with varied morbidity and mortality....
OBJECTIVE
Patients with non-ischaemic systolic heart failure (HF) and idiopathic dilated cardiomyopathy (DCM) are a heterogenous group with varied morbidity and mortality. Prognostication in this group is challenging. We performed a systematic review and meta-analysis to examine the significance of the presence of contractile reserve as assessed via stress imaging on mortality and hospitalisation.
METHODS
A search for studies that non-invasively assessed contractile reserve in patients with DCM or non-ischaemic HF with reduced ejection fraction, stress imaging with follow-up data comparing outcomes. A range of imaging modalities and stressors were included. We examined primary endpoints of mortality and secondary endpoints of combined cardiovascular events including HF progression or hospitalisation. Our analysis compared endpoints in patients with contractile reserve and those without it.
RESULTS
Nine prospective cohort studies were identified describing a total of 787 patients. These studies are methodologically but not statistically heterogenous ( = 31%). Using a random effect model, the presence of contractile reserve was associated with a significantly lower risk of mortality and cardiovascular events odds ratios of 0.20 (CI 0.11, 0.39) ( < 0.00001) and 0.13 (CI 0.04, 0.40) ( = 0.0004), respectively.
CONCLUSION
Regardless of stressor and imaging modality and despite the significant methodological heterogeneity within the current data (imaging techniques and parameters), patients with non-ischaemic cardiomyopathy and reduced EF who demonstrate contractile reserve have a lower mortality, and lower events/hospitalisations. The presence of contractile reserve therefore offers a potential positive prognostic indicator when managing these patients.
PubMed: 29258998
DOI: 10.1530/ERP-17-0054 -
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 -
JACC. Heart Failure Feb 2019To synthesize existing epidemiological data on cardiac dysfunction in HIV. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To synthesize existing epidemiological data on cardiac dysfunction in HIV.
BACKGROUND
Data on the burden and risk of human immunodeficiency virus (HIV) infection-associated cardiac dysfunction have not been adequately synthesized. We performed meta-analyses of extant literature on the frequency of several subtypes of cardiac dysfunction among people living with HIV.
METHODS
We searched electronic databases and reference lists of review articles and combined the study-specific estimates using random-effects model meta-analyses. Heterogeneity was explored using subgroup analyses and meta-regressions.
RESULTS
We included 63 reports from 54 studies comprising up to 125,382 adults with HIV infection and 12,655 cases of various cardiac dysfunctions. The pooled prevalence (95% confidence interval) was 12.3% (6.4% to 19.7%; 26 studies) for left ventricular systolic dysfunction (LVSD); 12.0% (7.6% to 17.2%; 17 studies) for dilated cardiomyopathy; 29.3% (22.6% to 36.5%; 20 studies) for grades I to III diastolic dysfunction; and 11.7% (8.5% to 15.3%; 11 studies) for grades II to III diastolic dysfunction. The pooled incidence and prevalence of clinical heart failure were 0.9 per 100 person-years (0.4 to 2.1 per 100 person-years; 4 studies) and 6.5% (4.4% to 9.6%; 8 studies), respectively. The combined prevalence of pulmonary hypertension and right ventricular dysfunction were 11.5% (5.5% to 19.2%; 14 studies) and 8.0% (5.2% to 11.2%; 10 studies), respectively. Significant heterogeneity was observed across studies for all the outcomes analyzed (I > 70%, p < 0.01), only partly explained by available study level characteristics. There was a trend for lower prevalence of LVSD in studies reporting higher antiretroviral therapy use or lower proportion of acquired immune deficiency syndrome. The prevalence of LVSD was higher in the African region. After taking into account the effect of regional variation, there was evidence of lower prevalence of LVSD in studies published more recently.
CONCLUSIONS
Cardiac dysfunction is frequent in people living with HIV. Additional prospective studies are needed to better understand the burden and risk of various forms of cardiac dysfunction related to HIV and the associated mechanisms. (Cardiac dysfunction in people living with HIV-a systematic review and meta-analysis; CRD42018095374).
Topics: Cardiomyopathies; Global Health; HIV; HIV Infections; Humans; Incidence; Risk Factors; Ventricular Function
PubMed: 30704613
DOI: 10.1016/j.jchf.2018.10.006 -
Circulation. Cardiovascular Imaging Jan 2020Although left ventricular noncompaction (LVNC) has been associated with an increased risk of adverse cardiovascular events, the accurate incidence of cardiovascular... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although left ventricular noncompaction (LVNC) has been associated with an increased risk of adverse cardiovascular events, the accurate incidence of cardiovascular morbidity and mortality is unknown. We, therefore, aimed to assess the incidence rate of LVNC-related cardiovascular events.
METHODS
We systematically searched observational studies reporting the adverse outcomes related to LVNC. The primary end point was cardiovascular mortality.
RESULTS
We identified 28 eligible studies enrolling 2501 LVNC patients (mean age, 46 years; male/female ratio, 1.7). After a median follow-up of 2.9 years, the pooled event rate for cardiovascular mortality was 1.92 (95% CI, 1.54-2.30) per 100 person-years. LVNC patients had a similar risk of cardiovascular mortality compared with a dilated cardiomyopathy control group (odds ratio, 1.10 [95% CI, 0.18-6.67]). The incidence rates of all-cause mortality, stroke and systemic emboli, heart failure admission, cardiac transplantation, ventricular arrhythmias, and cardiac device implantation were 2.16, 1.54, 3.53, 1.24, 2.17, and 2.66, respectively, per 100 person-years. Meta-regression and subgroup analyses revealed that left ventricular ejection fraction, not the extent of left ventricular trabeculation, had an important influence on the variability of incidence rates. The risks of thromboembolism and ventricular arrhythmias in LVNC patients were similar to dilated cardiomyopathy patients. However, LVNC patients had a higher incidence of heart failure hospitalization than dilated cardiomyopathy patients.
CONCLUSIONS
Patients with LVNC carry a similar cardiovascular risk when compared with dilated cardiomyopathy patients. Left ventricular ejection fraction-a conventional indicator of heart failure severity, not the extent of trabeculation-appears to be an important determinant of adverse outcomes in LVNC patients. Registration: https://www.crd.york.ac.uk/PROSPERO/ Unique identifier: CRD42018096313.
Topics: Heart Function Tests; Humans; Isolated Noncompaction of the Ventricular Myocardium; Observational Studies as Topic; Prognosis; Risk Factors
PubMed: 31959004
DOI: 10.1161/CIRCIMAGING.119.009712 -
Malawi Medical Journal : the Journal of... Sep 2019Myocardial pathologies are significant causes of morbidity and mortality in patients worldwide. Ischemic and non-ischemic cardiomyopathies have become a worldwide...
BACKGROUND
Myocardial pathologies are significant causes of morbidity and mortality in patients worldwide. Ischemic and non-ischemic cardiomyopathies have become a worldwide epidemic of the 21st century with an increasing impact on health care systems. The 2012 European Society of Cardiology and 2013 American College of Cardiology Foundation/American Heart Association guidelines provide current therapy guidance to reduce mortality and morbidity.
METHODS
This was a systematic review involving cardiac magnetic resonance (CMR) studies for the diagnosis of cardiomyopathy from January 2013 to April 2017. Out of 62 reviewed studies, only 12 were included in our study.
RESULTS
The average sensitivity and specificity of CMR in the diagnosis of cardiomyopathy was 86.75% (95% confidence interval [CI], 70.30% to 92.58%) and 81.75% (95% CI, 73.0% to 87.6%), respectively, and the positive predictive and negative predictive values were 80.17% and 86.75%, respectively.
CONCLUSION
Despite some limitations, our study shows that CMR has high sensitivity, specificity, and positive predictive value in diagnosing different types of cardiomyopathy. CMR may be used to differentiate types of cardiomyopathy, accurately quantify the chamber dimensions, volumes, and cardiac function, which make it useful for prognosis as well.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cardiomyopathies; Contrast Media; Echocardiography; Gadolinium; Humans; Magnetic Resonance Imaging; Middle Aged; Predictive Value of Tests; Sensitivity and Specificity; Stroke Volume; Ventricular Function, Left
PubMed: 31839897
DOI: 10.4314/mmj.v31i3.14 -
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 -
Journal of Cardiovascular Magnetic... May 2020The clinical application of cardiovascular magnetic resonance (CMR) T and T mapping is currently limited as ranges for healthy and cardiac diseases are poorly defined.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The clinical application of cardiovascular magnetic resonance (CMR) T and T mapping is currently limited as ranges for healthy and cardiac diseases are poorly defined. In this meta-analysis we aimed to determine the weighted mean of T and T mapping values in patients with myocardial infarction (MI), heart transplantation, non-ischemic cardiomyopathies (NICM) and hypertension, and the standardized mean difference (SMD) of each population with healthy controls. Additionally, the variation of mapping outcomes between studies was investigated.
METHODS
The PRISMA guidelines were followed after literature searches on PubMed and Embase. Studies reporting CMR T or T values measured in patients were included. The SMD was calculated using a random effects model and a meta-regression analysis was performed for populations with sufficient published data.
RESULTS
One hundred fifty-four studies, including 13,804 patient and 4392 control measurements, were included. T values were higher in patients with MI, heart transplantation, sarcoidosis, systemic lupus erythematosus, amyloidosis, hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM) and myocarditis (SMD of 2.17, 1.05, 0.87, 1.39, 1.62, 1.95, 1.90 and 1.33, respectively, P < 0.01) compared with controls. T values in iron overload patients (SMD = - 0.54, P = 0.30) and Anderson-Fabry disease patients (SMD = 0.52, P = 0.17) did both not differ from controls. T values were lower in patients with MI and iron overload (SMD of - 1.99 and - 2.39, respectively, P < 0.01) compared with controls. T values in HCM patients (SMD = - 0.61, P = 0.22), DCM patients (SMD = - 0.54, P = 0.06) and hypertension patients (SMD = - 1.46, P = 0.10) did not differ from controls. Multiple CMR acquisition and patient demographic factors were assessed as significant covariates, thereby influencing the mapping outcomes and causing variation between studies.
CONCLUSIONS
The clinical utility of T and T mapping to distinguish affected myocardium in patients with cardiomyopathies or heart transplantation from healthy myocardium seemed to be confirmed based on this meta-analysis. Nevertheless, variation of mapping values between studies complicates comparison with external values and therefore require local healthy reference values to clinically interpret quantitative values. Furthermore, disease differentiation seems limited, since changes in T and T values of most cardiomyopathies are similar.
Topics: Cardiomyopathies; Diagnosis, Differential; Heart Failure; Heart Transplantation; Humans; Hypertension; Magnetic Resonance Imaging; Myocardial Infarction; Predictive Value of Tests; Risk Factors; Treatment Outcome
PubMed: 32393281
DOI: 10.1186/s12968-020-00627-x -
The Cochrane Database of Systematic... Oct 2018The dystrophinopathies include Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and X-linked dilated cardiomyopathy (XLDCM). In recent years,...
BACKGROUND
The dystrophinopathies include Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and X-linked dilated cardiomyopathy (XLDCM). In recent years, co-ordinated multidisciplinary management for these diseases has improved the quality of care, with early corticosteroid use prolonging independent ambulation, and the routine use of non-invasive ventilation signficantly increasing survival. The next target to improve outcomes is optimising treatments to delay the onset or slow the progression of cardiac involvement and so prolong survival further.
OBJECTIVES
To assess the effects of interventions for preventing or treating cardiac involvement in DMD, BMD, and XLDCM, using measures of change in cardiac function over six months.
SEARCH METHODS
On 16 October 2017 we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE and Embase, and on 12 December 2017, we searched two clinical trials registries. We also searched conference proceedings and bibliographies.
SELECTION CRITERIA
We considered only randomised controlled trials (RCTs), quasi-RCTs and randomised cross-over trials for inclusion. In the Discussion, we reviewed open studies, longitudinal observational studies and individual case reports but only discussed studies that adequately described the diagnosis, intervention, pretreatment, and post-treatment states and in which follow-up lasted for at least six months.
DATA COLLECTION AND ANALYSIS
Two authors independently reviewed the titles and abstracts identified from the search and performed data extraction. All three authors assessed risk of bias independently, compared results, and decided which trials met the inclusion criteria. They assessed the certainty of evidence using GRADE criteria.
MAIN RESULTS
We included five studies (N = 205) in the review; four studies included participants with DMD only, and one study included participants with DMD or BMD. All studied different interventions, and meta-analysis was not possible. We found no studies for XLDCM. None of the trials reported cardiac function as improved or stable cardiac versus deteriorated.The randomised first part of a two-part study of perindopril (N = 28) versus placebo (N = 27) in boys with DMD with normal heart function at baseline showed no difference in the number of participants with a left ventricular ejection fraction (LVEF%) of less than 45% after three years of therapy (n = 1 in each group; risk ratio (RR) 1.04, 95% confidence interval (CI) 0.07 to 15.77). This result is uncertain because of study limitations, indirectness and imprecision. In a non-randomised follow-up study, after 10 years, more participants who had received placebo from the beginning had reduced LVEF% (less than 45%). Adverse event rates were similar between the placebo and treatment groups (low-certainty evidence).A study comparing treatment with lisinopril versus losartan in 23 boys newly diagnosed with Duchenne cardiomyopathy showed that after 12 months, both were equally effective in preserving or improving LVEF% (lisinopril 54.6% (standard deviation (SD) 5.19), losartan 55.2% (SD 7.19); mean difference (MD) -0.60% CI -6.67 to 5.47: N = 16). The certainty of evidence was very low because of very serious imprecision and study limitations (risk of bias). Two participants in the losartan group were withdrawn due to adverse events: one participant developed an allergic reaction, and a second exceeded the safety standard with a fall in ejection fraction greater than 10%. Authors reported no other adverse events related to the medication (N = 22; very low-certainty evidence).A study comparing idebenone versus placebo in 21 boys with DMD showed little or no difference in mean change in cardiac function between the two groups from baseline to 12 months; for fractional shortening the mean change was 1.4% (SD 4.1) in the idebenone group and 1.6% (SD 2.6) in the placebo group (MD -0.20%, 95% CI -3.07 to 2.67, N = 21), and for ejection fraction the mean change was -1.9% (SD 9.8) in the idebenone group and 0.4% (SD 5.5) in the placebo group (MD -2.30%, 95% CI -9.18 to 4.58, N = 21). The certainty of evidence was very low because of study limitations and very serious imprecision. Reported adverse events were similar between the treatment and placebo groups (low-certainty evidence).A multicentre controlled study added eplerenone or placebo to 42 patients with DMD with early cardiomyopathy but preserved left ventricular function already established on ACEI or ARB therapy. Results showed that eplerenone slowed the rate of decline of magnetic resonance (MR)-assessed left ventricular circumferential strain at 12 months (eplerenone group median 1.0%, interquartile range (IQR) 0.3 to -2.2; placebo group median 2.2%, IQR 1.3 to -3.1%; P = 0.020). The median decline in LVEF over the same period was also less in the eplerenone group (-1.8%, IQR -2.9 to 6.0) than in the placebo group (-3.7%, IQR -10.8 to 1.0; P = 0.032). We downgraded the certainty of evidence to very low for study limitations and serious imprecision. Serious adverse events were reported in two patients given placebo but none in the treatment group (very low-certainty evidence).A randomised placebo-controlled study of subcutaneous growth hormone in 16 participants with DMD or BMD showed an increase in left ventricular mass after three months' treatment but no significant improvement in cardiac function. The evidence was of very low certainty due to imprecision, indirectness, and study limitations. There were no clinically significant adverse events (very low-certainty evidence).Some studies were at risk of bias, and all were small. Therefore, although there is some evidence from non-randomised data to support the prophylactic use of perindopril for cardioprotection ahead of detectable cardiomyopathy, and for lisinopril or losartan plus eplerenone once cardiomyopathy is detectable, this must be considered of very low certainty. Findings from non-randomised studies, some of which have been long term, have led to the use of these drugs in daily clinical practice.
AUTHORS' CONCLUSIONS
Based on the available evidence from RCTs, early treatment with ACE inhibitors or ARBs may be comparably beneficial for people with a dystrophinopathy; however, the certainty of evidence is very low. Very low-certainty evidence indicates that adding eplerenone might give additional benefit when early cardiomyopathy is detected. No clinically meaningful effect was seen for growth hormone or idebenone, although the certainty of the evidence is also very low.
Topics: Adolescent; Adult; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Cardiomyopathies; Cardiomyopathy, Dilated; Cardiovascular Agents; Child; Disease Progression; Eplerenone; Human Growth Hormone; Humans; Lisinopril; Losartan; Male; Muscular Dystrophy, Duchenne; Non-Randomized Controlled Trials as Topic; Perindopril; Placebos; Randomized Controlled Trials as Topic; Stroke Volume; Ubiquinone; Young Adult
PubMed: 30326162
DOI: 10.1002/14651858.CD009068.pub3