scholarly journals Looking at New Unexpected Disease Targets in LMNA-Linked Lipodystrophies in the Light of Complex Cardiovascular Phenotypes: Implications for Clinical Practice

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 765
Author(s):  
Héléna Mosbah ◽  
Camille Vatier ◽  
Franck Boccara ◽  
Isabelle Jéru ◽  
Olivier Lascols ◽  
...  
Keyword(s):  
Ventricular Hypertrophy ◽  
Striated Muscle ◽  
Artery Bypass ◽  
Left Ventricular ◽  
The Novel ◽  
Partial Lipodystrophy ◽  
Non Invasive ◽  
Pathogenic Variants ◽  
Progeroid Syndromes ◽  
Function Testing

Variants in LMNA, encoding A-type lamins, are responsible for laminopathies including muscular dystrophies, lipodystrophies, and progeroid syndromes. Cardiovascular laminopathic involvement is classically described as cardiomyopathy in striated muscle laminopathies, and arterial wall dysfunction and/or valvulopathy in lipodystrophic and/or progeroid laminopathies. We report unexpected cardiovascular phenotypes in patients with LMNA-associated lipodystrophies, illustrating the complex multitissular pathophysiology of the disease and the need for specific cardiovascular investigations in affected patients. A 33-year-old woman was diagnosed with generalized lipodystrophy and atypical progeroid syndrome due to the newly identified heterozygous LMNA p.(Asp136Val) variant. Her complex cardiovascular phenotype was associated with atherosclerosis, aortic valvular disease and left ventricular hypertrophy with rhythm and conduction defects. A 29-year-old woman presented with a partial lipodystrophy syndrome and a severe coronary atherosclerosis which required a triple coronary artery bypass grafting. She carried the novel heterozygous p.(Arg60Pro) LMNA variant inherited from her mother, affected with partial lipodystrophy and dilated cardiomyopathy. Different lipodystrophy-associated LMNA pathogenic variants could target cardiac vasculature and/or muscle, leading to complex overlapping phenotypes. Unifying pathophysiological hypotheses should be explored in several cell models including adipocytes, cardiomyocytes and vascular cells. Patients with LMNA-associated lipodystrophy should be systematically investigated with 24-h ECG monitoring, echocardiography and non-invasive coronary function testing.

scholarly journals Diagnostic Ability of Peguero-Lo Presti Electrocardiographic Left Ventricular Hypertrophy Criterion in Severe Aortic Stenosis

2021 ◽  
Vol 10 (13) ◽  
pp. 2864
Author(s):  
Aleksandra Gamrat ◽  
Katarzyna Trojanowicz ◽  
Michał A. Surdacki ◽  
Aleksandra Budkiewicz ◽  
Adrianna Wąsińska ◽  
...  
Keyword(s):  
Left Ventricular Hypertrophy ◽  
Aortic Stenosis ◽  
Roc Curve ◽  
Ventricular Hypertrophy ◽  
Severe Aortic Stenosis ◽  
Positive Likelihood Ratio ◽  
Left Ventricular ◽  
The Novel ◽  
Operating Characteristics ◽  
Diagnostic Ability

Traditional electrocardiographic (ECG) criteria for left ventricular hypertrophy (LVH), introduced in the pre-echocardiographic era of diagnosis, have a relatively low sensitivity (usually not exceeding 25–40%) in detecting LVH. A novel Peguero-Lo Presti ECG-LVH criterion was recently shown to exhibit a higher sensitivity than the traditional ECG-LVH criteria in hypertension. Our aim was to test the diagnostic ability of the novel Peguero-Lo Presti ECG-LVH criterion in severe aortic stenosis. We retrospectively analyzed 12-lead ECG tracings and echocardiographic records from the index hospitalization of 50 patients with isolated severe aortic stenosis (mean age: 77 ± 10 years; 30 women and 20 men). Exclusion criteria included QRS > 120 ms, bundle branch blocks or left anterior fascicular block, a history of myocardial infarction, more than mild aortic or mitral regurgitation, and significant LV dysfunction by echocardiography. We compared the agreement of the novel Peguero-Lo Presti criterion and traditional ECG-LVH criteria with echocardiographic LVH (LV mass index > 95 g/m2 in women and >115 g/m2 in men). Echocardiographic LVH was found in 32 out of 50 study patients. The sensitivity of the Peguero-Lo Presti criterion in detecting LVH was improved (55% vs. 9–34%) at lower specificity (72% vs. 78–100%) in comparison to 8 single traditional ECG-LVH criteria. Additionally, the positive predictive value (77% vs. 72%), positive likelihood ratio (2.0 vs. 1.5), and odds ratio (3.2 vs. 2.4) were higher for the Peguero-Lo Presti criterion versus the presence of any of these 8 traditional ECG-LVH criteria. Cohen’s Kappa, a measure of concordance between ECG and echocardiography with regard to LVH, was 0.24 for the Peguero-Lo Presti criterion, −0.01–0.13 for single traditional criteria, and 0.20 for any traditional criterion. However, by the receiver operating characteristics (ROC) curve analysis, the overall ability to discriminate between patients with and without LVH was insignificantly lower for the Peguero-Lo Presti versus Cornell voltage as a continuous variable (area under the ROC curve: 0.65 (95% CI, 0.48–0.81) vs. 0.71 (0.55–0.86), p = 0.5). In conclusion, our preliminary results suggest a slightly better, albeit still low, agreement of the novel Peguero-Lo Presti ECG criterion compared to the traditional ECG-LVH criteria with echocardiographic LVH in severe aortic stenosis.

scholarly journals A novel nomogram to predict perioperative acute kidney injury following isolated coronary artery bypass grafting surgery with impaired left ventricular ejection fraction

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Hongyuan Lin ◽  
Jianfeng Hou ◽  
Hanwei Tang ◽  
Kai Chen ◽  
Hansong Sun ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Artery Bypass ◽  
Kidney Injury ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
The Novel ◽  
Net Benefit ◽  
Ventricular Ejection Fraction ◽  
Derivation Cohort ◽  
Postoperative Aki

Abstract Background and objective Heart failure (HF) is a global health issue, and coronary artery bypass graft (CABG) is one of the most effective surgical treatments for HF with coronary artery disease. Unfortunately, the incidence of postoperative acute kidney injury (AKI) is high in HF patients following CABG, and there are few tools to predict AKI after CABG surgery for such patients. The aim of this study is to establish a nomogram to predict the incidence of AKI after CABG in patients with impaired left ventricular ejection fraction (LVEF). Methods From 2012 to 2017, Clinical information of 1208 consecutive patients who had LVEF< 50% and underwent isolated CABG was collected to establish a derivation cohort. A novel nomogram was developed using the logistic regression model to predict postoperative AKI among these patients. According to the same inclusion criteria and the same period, we extracted the data of patients from 6 other large cardiac centers in China (n = 540) from the China Heart Failure Surgery Registry (China-HFSR) database for external validation of the new model. The nomogram was compared with 3 other available models predicting renal failure after cardiac surgery in terms of calibration, discrimination and net benefit. Results In the derivation cohort (n = 1208), 90 (7.45%) patients were diagnosed with postoperative AKI. The nomogram included 7 independent risk factors: female, increased preoperative creatinine(> 2 mg/dL), LVEF< 35%, previous myocardial infarction (MI), hypertension, cardiopulmonary bypass(CPB) used and perioperative blood transfusion. The area under the receiver operating characteristic curve (AUC) was 0.738, higher than the other 3 models. By comparing calibration curves and decision curve analyses (DCA) with other models, the novel nomogram showed better calibration and greater net benefit. Among the 540 patients in the validation cohort, 104 (19.3%) had postoperative AKI, and the novel nomogram performed better with respect to calibration, discrimination and net benefit. Conclusions The novel nomogram is a reliable model to predict postoperative AKI following isolated CABG for patients with impaired LVEF.

scholarly journals Diagnostic yield of hypertrophic cardiomyopathy in first-degree relatives of decedents with idiopathic left ventricular hypertrophy

EP Europace ◽  
2020 ◽  
Vol 22 (4) ◽  
pp. 632-642 ◽  
Author(s):  
Gherardo Finocchiaro ◽  
Harshil Dhutia ◽  
Belinda Gray ◽  
Bode Ensam ◽  
Stathis Papatheodorou ◽  
...  
Keyword(s):  
Ventricular Hypertrophy ◽  
Clinical Phenotype ◽  
Left Ventricular ◽  
Disease Entity ◽  
Long Qt ◽  
Molecular Autopsy ◽  
First Degree Relatives ◽  
Pathogenic Variants ◽  
The Family ◽  
Qt Syndrome

Abstract Aims Idiopathic left ventricular hypertrophy (LVH) is defined as LVH in the absence of myocyte disarray or secondary causes. It is unclear whether idiopathic LVH represents the phenotypic spectrum of hypertrophic cardiomyopathy (HCM) or whether it is a unique disease entity. We aimed to ascertain the prevalence of HCM in first-degree relatives of decedents from sudden death with idiopathic LVH at autopsy. Decedents also underwent molecular autopsy to identify the presence of pathogenic variants in genes implicated in HCM. Methods and results  Families of 46 decedents with idiopathic LVH (125 first-degree relatives) were investigated with electrocardiogram, echocardiogram exercise tolerance test, cardiovascular magnetic resonance imaging, 24-h Holter, and ajmaline provocation test. Next-generation sequencing molecular autopsy was performed in 14 (30%) cases. Decedents with idiopathic LVH were aged 33 ± 14 years and 40 (87%) were male. Fourteen families (30%) comprising 16 individuals were diagnosed with cardiac disease, including Brugada syndrome (n = 8), long QT syndrome (n = 3), cardiomyopathy (n = 2), and Wolff–Parkinson–White syndrome (n = 1). None of the family members were diagnosed with HCM. Molecular autopsy did not identify any pathogenic or likely pathogenic variants in genes encoding sarcomeric proteins. Two decedents had pathogenic variants associated with long QT syndrome, which were confirmed in relatives with the clinical phenotype. One decedent had a pathogenic variant associated with Danon disease in the absence of any histopathological findings of the condition or clinical phenotype in the family. Conclusion  Idiopathic LVH appears to be a distinct disease entity from HCM and is associated with fatal arrhythmias in individuals with primary arrhythmia syndromes. Family screening in relatives of decedents with idiopathic LVH should be comprehensive and encompass the broader spectrum of inherited cardiac conditions, including channelopathies.

scholarly journals Osteopontin as novel biomarker for reversibility of pressure overload induced left ventricular hypertrophy

2020 ◽  
Vol 14 (7) ◽  
pp. 513-523 ◽  
Author(s):  
Andreas Weber ◽  
Annalena L Büttner ◽  
Philipp Rellecke ◽  
Georgi Petrov ◽  
Alexander Albert ◽  
...  
Keyword(s):  
Plasma Levels ◽  
Prognostic Value ◽  
Ventricular Hypertrophy ◽  
Artery Bypass ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Bypass Grafting ◽  
Surgical Aortic Valve Replacement ◽  
Lv Mass ◽  
Eccentric Hypertrophy

Aim: The aim of this study was to evaluate the prognostic value of osteopontin (OPN) as a marker for left ventricular (LV) hypertrophy and its reversibility after surgical aortic valve replacement (SAVR). Patients & methods: Echocardiographic data and OPN plasma levels of 149 consecutive patients undergoing SAVR were obtained preoperatively and 3 months postoperatively. OPN was measured by Quantikine Human OPN immunoassay. Results: There was a significant correlation between higher OPN plasma levels and lower LV-mass regression. In patients receiving SAVR combined with coronary artery bypass grafting, high OPN plasma levels were also an indicator for eccentric hypertrophy phenotype. Conclusion: OPN may be a useful indicator for LV hypertrophy phenotype and could have a prognostic value to estimate LV-mass regression after SAVR.

scholarly journals Assessment of left ventricular myocardial work in Turner syndrome patients: insights from the novel non-invasive pressure-strain loop analysis method

2020 ◽  
Vol 10 (1) ◽  
pp. 15-25
Author(s):  
Felix Sebastian Oberhoffer ◽  
Hashim Abdul-Khaliq ◽  
Anna-Maria Jung ◽  
Michael Zemlin ◽  
Tilman R. Rohrer ◽  
...  
Keyword(s):  
Turner Syndrome ◽  
Left Ventricular ◽  
The Novel ◽  
Analysis Method ◽  
Loop Analysis ◽  
Non Invasive

A novel β-myosin heavy chain gene mutation, p.Met531Arg, identified in isolated left ventricular non-compaction in humans, results in left ventricular hypertrophy that progresses to dilation in a mouse model

2008 ◽  
Vol 114 (6) ◽  
pp. 431-440 ◽  
Author(s):  
Tomoya Kaneda ◽  
Chie Naruse ◽  
Atsuhiro Kawashima ◽  
Noboru Fujino ◽  
Toru Oshima ◽  
...  
Keyword(s):  
Mouse Model ◽  
Transgenic Mice ◽  
Dilated Cardiomyopathy ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Ventricular Hypertrophy ◽  
Left Ventricular ◽  
Chain Gene ◽  
The Novel ◽  
Sarcomeric Protein

Mutations in the βMHC (β-myosin heavy chain), a sarcomeric protein are responsible for hypertrophic and dilated cardiomyopathy. However, the mechanisms whereby distinct mutations in the βMHC gene cause two kinds of cardiomyopathy are still unclear. In the present study we report a novel βMHC mutation found in a patient with isolated LVNC [LV (left ventricular) non-compaction] and the phenotype of a mouse mutant model carrying the same mutation. To find the mutation responsible, we searched for genomic mutations in 99 unrelated probands with dilated cardiomyopathy and five probands with isolated LVNC, and identified a p.Met531Arg mutation in βMHC in a 13-year-old girl with isolated LVNC. Next, we generated six lines of transgenic mice carrying a p.Met532Arg mutant αMHC gene, which was identical with the p.Met531Arg mutation in the human βMHC. Among these, two lines with strong expression of the mutant αMHC gene were chosen for further studies. Although they did not exhibit the features characteristic of LVNC, approx. 50% and 70% of transgenic mice in each line displayed LVH (LV hypertrophy) by 2–3 months of age. Furthermore, LVD (LV dilation) developed in approx. 25% of transgenic mice by 18 months of age, demonstrating biphasic changes in LV wall thickness. The present study supports the idea that common mechanisms may be involved in LVH and LVD. The novel mouse model generated can provide important information for the understanding of the pathological processes and aetiology of cardiac dilation in humans.

Mild Left Ventricular Hypertrophy Unravels a Novel Nonsense Mutation of the GLA Gene Associated with the Classical Phenotype of Fabry Disease

Cardiology ◽  
2017 ◽  
Vol 137 (2) ◽  
pp. 67-73 ◽  
Author(s):  
Olga Azevedo ◽  
Miguel Gago ◽  
Gabriel Miltenberger-Miltenyi ◽  
Paulo Gaspar ◽  
Nuno Sousa ◽  
...  
Keyword(s):  
Left Ventricular Hypertrophy ◽  
Fabry Disease ◽  
Nonsense Mutation ◽  
Ventricular Hypertrophy ◽  
Large Family ◽  
Disease Diagnosis ◽  
Left Ventricular ◽  
The Novel ◽  
Complete Evaluation ◽  
Gla Gene

We report on the clinical, biochemical, and genetic findings of a large family with the classical phenotype of Fabry disease due to the novel nonsense mutation c.607G>T (p.E203X) of the GLA gene, which occurs in the active site of the α-galactosidase A enzyme. This report highlights that (i) Fabry disease diagnosis should be considered in all cases of unexplained left ventricular hypertrophy (LVH), even in its milder forms; (ii) a complete evaluation of patients with unexplained LVH is important to find diagnostic red flags of treatable causes of LVH, such as Fabry disease; (iii) cascade family screening is paramount to the earlier diagnosis and treatment of other affected family members; and (iv) the Fabry disease phenotype is highly variable in heterozygote females, even within the same family.

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