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International Journal of Cardiology Sep 2022Loeys-Dietz syndrome (LDS) is a connective tissue disorder that arises from mutations altering the transforming growth factor β signalling pathway. Due to the recent... (Review)
Review
INTRODUCTION
Loeys-Dietz syndrome (LDS) is a connective tissue disorder that arises from mutations altering the transforming growth factor β signalling pathway. Due to the recent discovery of the underlying genetic mutations leading to LDS, the spectrum of characteristics and complications is not fully understood.
METHODS
Our search included five databases (Pubmed, SCOPUS, Web of Science, EMBASE and google scholar) and included variations of "Loeys-Dietz Syndrome" as search terms, using all available data until February 2021. All study types were included. Three reviewers screened 1394 abstracts, of which 418 underwent full-text review and 392 were included in the final analysis.
RESULTS
We identified 3896 reported cases of LDS with the most commonly reported features and complications being: aortic aneurysms and dissections, arterial tortuosity, high arched palate, abnormal uvula and hypertelorism. LDS Types 1 and 2 share many clinical features, LDS Type 2 appears to have a more aggressive aortic disease. LDS Type 3 demonstrated an increased prevalence of mitral valve prolapse and arthritis. LDS Type 4 and 5 demonstrated a lower prevalence of musculoskeletal and cardiovascular involvement. Amongst 222 women who underwent 522 pregnancies, 4% experienced an aortic dissection and the peripartum mortality rate was 1%.
CONCLUSION
We observed that LDS is a multisystem connective tissue disorder that is associated with a high burden of complications, requiring a multidisciplinary approach. Ongoing attempts to better characterise these features will allow clinicians to appropriately screen and manage these complications.
Topics: Aortic Dissection; Arteries; Connective Tissue Diseases; Female; Humans; Loeys-Dietz Syndrome; Mutation; Pregnancy
PubMed: 35662564
DOI: 10.1016/j.ijcard.2022.05.065 -
Journal of the American Heart... Dec 2018Background The relationship between mitral valve prolapse ( MVP ) and sudden cardiac death ( SCD ) remains controversial. In this systematic review, we evaluate the...
Background The relationship between mitral valve prolapse ( MVP ) and sudden cardiac death ( SCD ) remains controversial. In this systematic review, we evaluate the relationship between isolated MVP and SCD to better define a potential high-risk subtype. In addition, we determine whether premortem parameters could predict SCD in patients with MVP and the incidence of SCD in MVP . Methods and Results Electronic searches were conducted in PubMed and Embase for all English literature articles published between 1960 and 2018 regarding MVP and SCD or cardiac arrest. We also identified articles investigating predictors of ventricular arrhythmias or SCD and cohort studies reporting SCD outcomes in MVP . From 2180 citations, there were 79 articles describing 161 cases of MVP with SCD or cardiac arrest. The median age was 30 years and 69% of cases were female. Cardiac arrest occurred during situations of stress in 47% and was caused by ventricular fibrillation in 81%. Premature ventricular complexes on Holter monitoring (92%) were common. Most cases had bileaflet involvement (70%) with redundancy (99%) and nonsevere mitral regurgitation (83%). From 22 articles describing predictors for ventricular arrhythmias or SCD in MVP , leaflet redundancy was the only independent predictor of SCD . The incidence of SCD with MVP was estimated at 217 events per 100 000 person-years. Conclusions Isolated MVP and SCD predominantly affects young females with redundant bileaflet prolapse, with cardiac arrest usually occurring as a result of ventricular arrhythmias. To better understand the complex relationship between MVP and SCD , standardized reporting of clinical, electrophysiological, and cardiac imaging parameters with longitudinal follow-up is required.
Topics: Death, Sudden, Cardiac; Humans; Mitral Valve Prolapse; Risk Factors
PubMed: 30486705
DOI: 10.1161/JAHA.118.010584 -
Cureus Dec 2021The presence of mitral valve prolapse (MVP) varies from asymptomatic to life-threatening arrhythmias. Catheter ablation (CA) is widely used to treat ventricular... (Review)
Review
The presence of mitral valve prolapse (MVP) varies from asymptomatic to life-threatening arrhythmias. Catheter ablation (CA) is widely used to treat ventricular arrhythmias (VAs) associated with MVP. Despite having high procedural success, outcome data after CA is limited, especially in a long-term setting. Therefore, this systematic review and meta-analysis were performed. Literature searching was conducted in Pubmed, EuropePMC, Proquest, and Ebsco from inception to December 2020 using keywords: ventricular arrhythmia, premature ventricular complex, ventricular tachycardia, ventricular fibrillation, mitral valve prolapse, and catheter ablation. A total of 407 potential articles were retrieved for further review. The final review resulted in six articles for systematic review and meta-analysis. The study was registered in PROSPERO (CRD42020219144). The most common origin of VAs was papillary muscle. The acute success rate of CA in the MVP group varies between 66% and 94%. Follow-up studies reported a higher percentage of VAs recurrence after CA in the MVP group (22.22%) compared with the non-MVP group (11.38%). However, the difference is not significant (P-value = 0.16). Other studies reported a 12.5%-36% rate and 40% of repeat ablation in the medium term and the long term, respectively. Episodes of sudden cardiac death during exertion could still occur following CA in patients with MVP. Distinct origin of VAs was observed during repeated ablation procedures, which may explain arrhythmic substrate progression. Diffuse left ventricular fibrosis around papillary muscle rather than local fibrosis was observed among older patients. Furthermore, the presence of mitral annular disjunction (MAD) and Filamin C mutation might increase the risk of recurrent VAs. CAn has been done as the treatment of VAs associated with MVP. The acute success rate of CA varies between studies and the number of patients requiring repeat CA varied from 12.5% to 40%. Sudden cardiac death could still occur after CA. Older age during CA, genetic predisposition, deep arrhythmic foci, multifocal VAs origin, diffuse fibrosis, and the presence of MAD may contribute to the recurrence of VAs. Further studies, stratification, and evaluation are needed to prevent fatal outcomes in VA associated with MVP, even after CA.
PubMed: 35024259
DOI: 10.7759/cureus.20310 -
The Journal of Thoracic and... Jan 2018To compare outcomes of chordal replacement versus leaflet resection techniques for repair of isolated posterior mitral leaflet prolapse. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To compare outcomes of chordal replacement versus leaflet resection techniques for repair of isolated posterior mitral leaflet prolapse.
METHODS
We searched MEDLINE and EMBASE databases for studies that compared chordal replacement ("neo-chord" group) versus leaflet resection ("resection" group) techniques for the treatment of posterior mitral leaflet prolapse. Data were extracted by 2 independent investigators and subjected to a meta-analysis using a random-effects model.
RESULTS
One randomized controlled trial (RCT), 1 propensity-matched study, and 6 unadjusted observational studies, with a total of 1926 patients, met our inclusion criteria. Two studies reported only perioperative outcomes; mean follow-up ranged from 1.0 to 5.9 years in the remaining studies. In pooled data from unadjusted observational studies, annuloplasty ring diameter was higher in the neo-chord group (+1.5 mm; P = .0003), but with high heterogeneity (I = 91%). Based on limited data, postprocedural left ventricular ejection fraction may be greater in the neo-chord group, but this difference reached statistical significance only in the RCT (+3.4%; P = .03), and not in 2 observational studies that reported this outcome (+2.7%; P = .10). There was no difference in recurrent mitral regurgitation at follow-up between the resection and neo-chord groups; however, patients in the neo-chord group had a lower rate of mitral valve reoperation at follow-up in the unadjusted observational studies (incidence rate ratio, 0.22; P = .0008 [I = 0%; 4 studies, 1331 patients]).
CONCLUSIONS
Chordal replacement may be associated with greater freedom from reoperation and may lead to improved postoperative left ventricular function compared with leaflet resection. However, these conclusions are supported primarily by data from unadjusted observational studies, and high-quality RCTs of chordal replacement versus leaflet resection are needed.
Topics: Cardiac Surgical Procedures; Chordae Tendineae; Humans; Mitral Valve Prolapse; Outcome and Process Assessment, Health Care
PubMed: 28967416
DOI: 10.1016/j.jtcvs.2017.07.078 -
Annals of Cardiothoracic Surgery Nov 2013Robotic telemanipulators have evolved to assist the challenges of minimally invasive mitral valve surgery (MVS). A systematic review was performed to provide a synopsis... (Review)
Review
BACKGROUND
Robotic telemanipulators have evolved to assist the challenges of minimally invasive mitral valve surgery (MVS). A systematic review was performed to provide a synopsis of the literature, focusing on clinical outcomes and cost-effectiveness.
METHOD
Structured searches of MEDLINE, Embase, and Cochrane databases were performed in August 2013. All original studies except case-reports were included in qualitative review. Studies with ≥50 patients were presented quantitatively.
RESULTS
After applying inclusion and exclusion criteria to the search results, 27 studies were included in qualitative review, 16 of which had ≥50 patients. All studies were observational in nature, and thus the quality of evidence was rated low to medium. Patients generally had good left ventricular performance, were relatively asymptomatic, and mean patient age ranged from 52.6-58.4 years. Rates of intraoperative outcomes ranged from: 0.0-9.1% for conversion to non-robotic surgery, 106±22 to 188.5±53.8 min for cardiopulmonary bypass (CPB) time and 79±16 to 140±40 min for cross-clamp (XC) time. Rates of short-term postoperative outcomes ranged from: 0.0-3.0% for mortality, 0.0-3.2% for myocardial infarction (MI), 0.0-3.0% for permanent stroke, 1.6-15% for pleural effusion, 0.0-5.0% for reoperations for bleeding, 0.0-0.3% for infection, and 1.1-6% for prolonged ventilation (>48 hours), 1.5-5.4% for early repair failure, 12.3±6.7 to 36.6±24.7 hours for intensive care length of stay, 3.1±0.3 to 6.3±3.9 days for hospital length of stay (HLOS) and 81.7-97.6% had no or trivial mitral regurgitation (MR) before discharge.
CONCLUSIONS
All subtypes of mitral valve prolapse are repairable with robotic techniques. CPB and XC times are long, and novel techniques such as the Cor-Knot, Nitinol clips or running sutures may reduce the time required. The overall rates of early postoperative mortality and morbidity are low. Improvements in postoperative quality of life (QoL) and expeditious return to work offset the increase in equipment and intraoperative cost. Evidence for long-term outcomes is as yet limited.
PubMed: 24349971
DOI: 10.3978/j.issn.2225-319X.2013.10.18 -
Frontiers in Cardiovascular Medicine 2021Evaluate the evidence on the abnormalities of the aortic root and heart valves, risk and prognostic factors for heart valve disease and valve replacement surgery in...
Evaluate the evidence on the abnormalities of the aortic root and heart valves, risk and prognostic factors for heart valve disease and valve replacement surgery in spondyloarthritis. A systematic literature review was performed using Medline, EMBASE and Cochrane databases until July 2021. Prevalence, incidence, risk and prognostic factors for heart valve disease; dimension, morphology, and pathological abnormalities of the valves were analyzed. Patient characteristics (younger age, history of cardiac disease or longer disease duration) and period of realization were considered for the analysis. The SIGN Approach was used for rating the quality of the evidence of the studies. In total, 37 out of 555 studies were included. Overall, the level of evidence was low. The incidence of aortic insufficiency was 2.5-3.9‰. Hazard Ratio for aortic insufficiency was 1.8-2.0. Relative risk for aortic valve replacement surgery in ankylosing spondylitis patients was 1.22-1.46. Odds ratio for aortic insufficiency was 1.07 for age and 1.05 for disease duration. Mitral valve abnormalities described were mitral valve prolapse, calcification, and thickening. Aortic valve abnormalities described were calcification, thickening and an echocardiographic "subaortic bump." Abnormalities of the aorta described were thickening of the wall and aortic root dilatation. The most common microscopic findings were scarring of the adventitia, lymphocytic infiltration, and intimal proliferation. A higher prevalence and risk of aortic valve disease is observed in patients with ankylosing spondylitis. Studies were heterogeneous and analysis was not adjusted by potential confounders. Most studies did not define accurate outcomes and may have detected small effects as being statistically significant.
PubMed: 34631824
DOI: 10.3389/fcvm.2021.719523 -
Annals of Cardiothoracic Surgery May 2015Discordance between studies drives continued debate regarding the best management of asymptomatic severe mitral regurgitation (MR). The aim of the present study was to... (Review)
Review
BACKGROUND
Discordance between studies drives continued debate regarding the best management of asymptomatic severe mitral regurgitation (MR). The aim of the present study was to conduct a systematic review and meta-analysis of management plans for asymptomatic severe MR, and compare the effectiveness of a strategy of early surgery to watchful waiting.
METHODS
A systematic review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Studies were excluded if they: (I) lacked a watchful waiting cohort; (II) included symptomatic patients; or (III) included etiologies other than degenerative mitral valve disease. The primary outcome of the study was all-cause mortality at 10 years. Secondary outcomes included operative mortality, repair rate, repeat mitral valve surgery, and development of new atrial fibrillation.
RESULTS
Five observational studies were eligible for review and three were included in the pooled analysis. In asymptomatic patients without class I triggers (symptoms or ventricular dysfunction), pooled analysis revealed a significant reduction in long-term mortality with an early surgery approach [hazard ratio (HR) =0.38; 95% confidence interval (CI): 0.21-0.71]. This survival benefit persisted in a sub-group analysis limited to patients without class II triggers (atrial fibrillation or pulmonary hypertension) [relative risk (RR) =0.85; 95% CI: 0.75-0.98]. Aggregate rates of operative mortality did not differ between treatment arms (0.7% vs. 0.7% for early surgery vs. watchful waiting). However, significantly higher repair rates were achieved in the early surgery cohorts (RR =1.10; 95% CI: 1.02-1.18).
CONCLUSIONS
Despite disagreement between individual studies, the present meta-analysis demonstrates that a strategy of early surgery may improve survival and increase the likelihood of mitral valve repair compared with watchful waiting. Early surgery may also benefit patients when instituted prior to the development of class II triggers.
PubMed: 26309823
DOI: 10.3978/j.issn.2225-319X.2015.04.01 -
BMC Cardiovascular Disorders Feb 2018Myxomatous mitral valve prolapse is a common cardiac abnormality. Morbus Barlow is characterized by excess myxomatous leaflet tissue, bileaflet prolapse or billowing,...
BACKGROUND
Myxomatous mitral valve prolapse is a common cardiac abnormality. Morbus Barlow is characterized by excess myxomatous leaflet tissue, bileaflet prolapse or billowing, chordae elongation and annular dilatation with or without calcification. Extensive myxoid degeneration with destruction of the normal three-layered leaflet tissue architecture is observed histologically in such patients. Autosomal dominant inheritance with an age and sex-dependent expression has long been recognised. This review explores the current understanding of the genetics of bileaflet prolapse, with a focus on genetic analysis and the role for echocardiographical screening of the first degree relatives of affected patients.
METHODS
Systematic literature searches were performed using PubMed and Embase up to September 2017. In Disse et al.'s study (study one) first degree relatives of 25 patients with Morbus Barlow who underwent mitral valve repair were screened for bileaflet valve prolapse. In Nesta et al.'s study one family with three living generations of 43 individuals with 9 confirmed cases of MVP was screened. Genotyping was performed in four families for 344 microsatellite markers from Chromosome 1 to 16.
RESULTS
In study one, autosomal dominant inheritance was shown in four pedigrees. Genome-wide linkage analysis of the most informative pedigree (24 individuals, three generations) showed a significant linkage for markers mapping to chromosome 16p. Linkage to this locus was confirmed in a second family within the same study, but was excluded in the remaining two pedigrees. In study two an autosomal dominant locus was mapped to chromosome 13. 8 of the 9 individuals affected were found to suffer from bileaflet prolapse.
CONCLUSIONS
Barlow's disease is a heritable trait but the genetic causes remain largely elusive. Ch16p11.2-p12.1 is the only locus proven to be associated with bileaflet prolapse. Locus 13.q31.3-q32.1 was shown to cause bileaflet as well as posterior leaflet prolapse. This review intends to make physicians aware of genetic causes of myxomatous mitral valve prolapse, thereby emphasising the importance of cardiological examination of first-degree relatives of patients with Morbus Barlow. Integrated and more comprehensive studies are needed for identification of genes involved in this heterogenic disease. Further genomic studies may facilitate more individualised and accurate risk assessment and may help to develop possible preventive stategies for patients in the future.
Topics: Adult; Echocardiography; Female; Genetic Markers; Genetic Predisposition to Disease; Genome-Wide Association Study; Heredity; Humans; Male; Middle Aged; Mitral Valve; Mitral Valve Prolapse; Pedigree; Prognosis; Risk Factors
PubMed: 29486707
DOI: 10.1186/s12872-018-0755-y -
Frontiers in Cardiovascular Medicine 2022Mitral valve prolapse (MVP) due to myxomatous degeneration is one of the most important chronic degenerative cardiovascular diseases in people and dogs. It is a common...
Mitral valve prolapse (MVP) due to myxomatous degeneration is one of the most important chronic degenerative cardiovascular diseases in people and dogs. It is a common cause of heart failure leading to significant morbidity and mortality in both species. Human MVP is usually classified into primary or non-syndromic, including Barlow's Disease (BD), fibro-elastic deficiency (FED) and Filamin-A mutation, and secondary or syndromic forms (typically familial), such as Marfan syndrome (MFS), Ehlers-Danlos syndrome, and Loeys-Dietz syndrome. Despite different etiologies the diseased valves share pathological features consistent with myxomatous degeneration. To reflect this common pathology the condition is often called myxomatous mitral valve degeneration (disease) (MMVD) and this term is universally used to describe the analogous condition in the dog. MMVD in both species is characterized by leaflet thickening and deformity, disorganized extracellular matrix, increased transformation of the quiescent valve interstitial cell (qVICs) to an activated state (aVICs), also known as activated myofibroblasts. Significant alterations in these cellular activities contribute to the initiation and progression of MMVD due to the increased expression of transforming growth factor-β (TGF-β) superfamily cytokines and the dysregulation of the TGF-β signaling pathways. Further understanding the molecular mechanisms of MMVD is needed to identify pharmacological manipulation strategies of the signaling pathway that might regulate VIC differentiation and so control the disease onset and development. This review briefly summarizes current understanding of the histopathology, cellular activities, molecular mechanisms and pathogenesis of MMVD in dogs and humans, and in more detail reviews the evidence for the role of TGF-β.
PubMed: 35656405
DOI: 10.3389/fcvm.2022.872288 -
Diagnostics (Basel, Switzerland) Sep 2020Marfan syndrome (MFS) is a heritable systemic connective tissue disease with important cardiovascular involvement, including aortic root dilatation and mitral valve... (Review)
Review
Marfan syndrome (MFS) is a heritable systemic connective tissue disease with important cardiovascular involvement, including aortic root dilatation and mitral valve prolapse. Life expectancy in patients with MFS is mainly determined by cardiovascular complications, among which aortic dissection or rupture are most dreaded. In recent years, heart failure and ventricular arrhythmia have drawn attention as extra-aortic cardiovascular manifestations and as additional reported causes of death. Imaging studies have provided data supporting a primary myocardial impairment in the absence of valvular disease or cardiovascular surgery, while studies using ambulatory ECG have demonstrated an increased susceptibility to ventricular arrhythmia. In this paper, current literature was reviewed in order to provide insights in characteristics, pathophysiology and evolution of myocardial function, heart failure and ventricular arrhythmia in MFS.
PubMed: 32992882
DOI: 10.3390/diagnostics10100751