Left ventricular non-compaction: clinical features and cardiovascular magnetic resonance imaging

Background: It is apparent that despite lack of family history, patients with the morphological characteristics of left ventricular non-compaction develop arrhythmias, thrombo-embolism and left ventricular dysfunction. METHODS: Forty two patients, aged 48.7 +/- 2.3 yrs (mean +/- SEM) underwent cardiovascular magnetic resonance (CMR) for the quantification of left ventricular volumes and extent of non-compacted (NC) myocardium. The latter was quantified using planimetry on the two-chamber long axis LV view (NC area). The patients included those referred specifically for CMR to investigate suspected cardiomyopathy, and as such is represents a selected group of patients. RESULTS: At presentation, 50% had dyspnoea, 19% chest pain, 14% palpitations and 5% stroke. Pulmonary embolism had occurred in 7% and brachial artery embolism in 2%. The ECG was abnormal in 81% and atrial fibrillation occurred in 29%. Transthoracic echocardiograms showed features of NC in only 10%. On CMR, patients who presented with dyspnoea had greater left ventricular volumes (both p < 0.0001) and a lower left ventricular ejection fraction (LVEF) (p < 0.0001) than age-matched, healthy controls. In patients without dyspnoea (n = 21), NC area correlated positively with end-diastolic volume (r = 0.52, p = 0.0184) and end-systolic volume (r = 0.56, p = 0.0095), and negatively with EF (r = -0.72, p = 0.0001). CONCLUSION: Left ventricular non-compaction is associated with dysrrhythmias, thromboembolic events, chest pain and LV dysfunction. The inverse correlation between NC area and EF suggests that NC contributes to left ventricular dysfunction

Impact of functional studies on exome sequence variant interpretation in early-onset cardiac conduction system diseases

Aims The genetic cause of cardiac conduction system disease (CCSD) has not been fully elucidated. Whole-exome sequencing (WES) can detect various genetic variants; however, the identification of pathogenic variants remains a challenge. We aimed to identify pathogenic or likely pathogenic variants in CCSD patients by using WES and 2015 American College of Medical Genetics and Genomics (ACMG) standards and guidelines as well as evaluating the usefulness of functional studies for determining them. Methods and Results We performed WES of 23 probands diagnosed with early-onset (&amp;lt;65 years) CCSD and analyzed 117 genes linked to arrhythmogenic diseases or cardiomyopathies. We focused on rare variants (minor allele frequency &amp;lt; 0.1%) that were absent from population databases. Five probands had protein truncating variants in EMD and LMNA which were classified as “pathogenic” by 2015 ACMG standards and guidelines. To evaluate the functional changes brought about by these variants, we generated a knock-out zebrafish with CRISPR-mediated insertions or deletions of the EMD or LMNA homologs in zebrafish. The mean heart rate and conduction velocities in the CRISPR/Cas9-injected embryos and F2 generation embryos with homozygous deletions were significantly decreased. Twenty-one variants of uncertain significance were identified in 11 probands. Cellular electrophysiological study and in vivo zebrafish cardiac assay showed that 2 variants in KCNH2 and SCN5A, 4 variants in SCN10A, and 1 variant in MYH6 damaged each gene, which resulted in the change of the clinical significance of them from “Uncertain significance” to “Likely pathogenic” in 6 probands. Conclusions Of 23 CCSD probands, we successfully identified pathogenic or likely pathogenic variants in 11 probands (48%). Functional analyses of a cellular electrophysiological study and in vivo zebrafish cardiac assay might be useful for determining the pathogenicity of rare variants in patients with CCSD. SCN10A may be one of the major genes responsible for CCSD. Translational Perspective Whole-exome sequencing (WES) may be helpful in determining the causes of cardiac conduction system disease (CCSD), however, the identification of pathogenic variants remains a challenge. We performed WES of 23 probands diagnosed with early-onset CCSD, and identified 12 pathogenic or likely pathogenic variants in 11 of these probands (48%) according to the 2015 ACMG standards and guidelines. In this context, functional analyses of a cellular electrophysiological study and in vivo zebrafish cardiac assay might be useful for determining the pathogenicity of rare variants, and SCN10A may be one of the major development factors in CCSD

Only Elongated Chordae Tendineae is Important Entity of MVP Syndrome

Back ground Mitral valve prolapse [MVP ]is the most common valvluar abnormities . Echocardiographically MVP classified to two types, classical MVP ,more commonly occur in male after age of 40 years and usually associated with complications and non-classical MVP, usually in young female and usually benign , but commonly associated with autonomic dysfunction [MVP syndrome ]. Method 2676 patients (1985 female Vs. 691 male), their age between 12—81 year, were referred for ECHO study because of clinical suspicion of MVP, 2-D Color-Doppler ECHO study in left parasternal long axis view was done for them in addition to 12-lead ECG, patients were triage as group 1. classical MVP [define as more than 2mm displacement of mitral valve leaflet in to left atrium in addition to leaflet thickness 5mm or more] 2. Non-classical MVP [ 2 mm or more displacement with leaflet thickness less than 5mm.] 3. This group show no displacement with normal thickness of leaflet but show only elongated and fluttering chordae tendinae labeled as only elongated chordae group and group 4 which show completely normal ECHO [ labeled as non-prolapsing MVP syndrome],this group was excluded from the study. Result 283 patients [31.58%] have classical MVP [122 female vs. 151 male], 315 patients [35.1%] show non-classical MVP [236 female vs.79 male] while 298 patients [33.25%] show only elongated chordae [216 female vs. 82 male]. While 1780 patients [66.51%] have normal ECHO [ non prolapsing MVP syndrome. Mitral regurgitation [MR] occure in 203 patients of classical MVP [71.73%] (36 female vs. 167 male) while 132 patients (42%) [89 female vs.43 male] of non-classical MVP have MR and only 6 patients (2%) [5 female vs. 1 male] with only elongated chordae show MR. Conclusion Most patients with clinical suspicion of MVP have no evidence of prolapsed by ECHO study, those with ECHO finding may show either classical or non—classical MVP. Significant number of patients show only elongated chordae tendinae without prolapsed. So elonongated chordate can consider as important cause of MVP syndrome

Gender-Related Differences in the Prevalence of Cardiovascular Disease Risk Factors and their Correlates in Urban Tanzania.

\ud Urban areas in Africa suffer a serious problem with dual burden of infectious diseases and emerging chronic diseases such as cardiovascular diseases (CVD) and diabetes which pose a serious threat to population health and health care resources. However in East Africa, there is limited literature in this research area. The objective of this study was to examine the prevalence of cardiovascular disease risk factors and their correlates among adults in Temeke, Dar es Salaam, Tanzania. Results of this study will help inform future research and potential preventive and therapeutic interventions against such chronic diseases. The study design was a cross sectional epidemiological study. A total of 209 participants aged between 44 and 66 years were included in the study. A structured questionnaire was used to evaluate socioeconomic and lifestyle characteristics. Blood samples were collected and analyzed to measure lipid profile and fasting glucose levels. Cardiovascular risk factors were defined using World Health Organization criteria. The age-adjusted prevalence of obesity (BMI > or = 30) was 13% and 35%, among men and women (p = 0.0003), respectively. The prevalence of abdominal obesity was 11% and 58% (p < 0.0001), and high WHR (men: >0.9, women: >0.85) was 51% and 73% (p = 0.002) for men and women respectively. Women had 4.3 times greater odds of obesity (95% CI: 1.9-10.1), 14.2-fold increased odds for abdominal adiposity (95% CI: 5.8-34.6), and 2.8 times greater odds of high waist-hip-ratio (95% CI: 1.4-5.7), compared to men. Women had more than three-fold greater odds of having metabolic syndrome (p = 0.001) compared to male counterparts, including abdominal obesity, low HDL-cholesterol, and high fasting blood glucose components. In contrast, female participants had 50% lower odds of having hypertension, compared to men (95%CI: 0.3-1.0). Among men, BMI and waist circumference were significantly correlated with blood pressure, triglycerides, total, LDL-, and HDL-cholesterol (BMI only), and fasting glucose; in contrast, only blood pressure was positively associated with BMI and waist circumference in women. The prevalence of CVD risk factors was high in this population, particularly among women. Health promotion, primary prevention, and health screening strategies are needed to reduce the burden of cardiovascular disease in Tanzania.\u

Morphofunctional abnormalities of mitral annulus and arrhythmic mitral valve prolapse

Background\u2014Arrhythmic mitral valve prolapse (MVP) is characterized by myxomatous leaflets and left ventricular (LV) fibrosis of papillary muscles and inferobasal wall. We searched for morphofunctional abnormalities of the mitral valve that could explain a regional mechanical myocardial stretch. Methods and Results\u2014Thirty-six (27 female patients; median age: 44 years) arrhythmic MVP patients with LV late gadolinium enhancement on cardiac magnetic resonance and no or trivial mitral regurgitation, and 16 (6 female patients; median age: 40 years) MVP patients without LV late gadolinium enhancement were investigated by morphofunctional cardiac magnetic resonance. Mitral annulus disjunction (median: 4.8 versus 1.8 mm; P1.5 (22 [61%] versus 4 [25%]; P=0.016) were higher in MVP patients with late gadolinium enhancement than in those without. A linear correlation was found between mitral annulus disjunction and curling (R=0.85). A higher prevalence of auscultatory midsystolic click (26 [72%] versus 6 [38%]; P=0.018) was also noted. Histology of the mitral annulus showed a longer mitral annulus disjunction in 50 sudden death patients with MVP and LV fibrosis than in 20 patients without MVP (median: 3 versus 1.5 mm; P<0.001). Conclusions\u2014Mitral annulus disjunction is a constant feature of arrhythmic MVP with LV fibrosis. The excessive mobility of the leaflets caused by posterior systolic curling accounts for a mechanical stretch of the inferobasal wall and papillary muscles, eventually leading to myocardial hypertrophy and scarring. These mitral annulus abnormalities, together with auscultatory midsystolic click, may identify MVP patients who would need arrhythmic risk stratification

Mitral valve prolapse: Comparative Value of M-mode, two-dimensional and doppler echocardiography

M-mode, two-dimensional and Doppler echocardiography were used to assess the comparative value of each in the detection of clinically diagnosed mitral valve prolapse; 125 consecutive patients with a mid- to late systolic click, with or without a late systolic murmur, were included. There were 46 men and 79 women; their mean age was 42 years. M-mode echocardiography detected 62 of 125 cases (sensitivity 50%). Two-dimensional echo-cardiography was positive in 85 cases (sensitivity 68%) and 90 cases were detected with Doppler echocardiography (sensitivity 72%). When all three techniques were combined, 116 cases were correctly diagnosed (total echo-graphic sensitivity 93%). The relative insensitivity of the M-mode technique and the additive value of two-dimensional and Doppler echocardiography in the detection of auscultatory mitral prolapse are emphasized

Mitral Valve Prolapse

Mitral valve prolapse (MVP) is the most common valvular abnormality, affecting 2.4% of the population. Usually MVP is a benign disease and remains asymptomatic. The diagnosis of MVP is based on clinical presentation, physical examination and echocardiography. Some atypical symptoms that are not correlated with mitral valve function, are described as the MVP syndrome. Potential complications such as infective endocarditis, thromboembolic events, atrial and ventricular arrhythmias, and progressive mitral valve regurgitation may occur. Management should concentrate on adequate guidance of the patients, relief of symptoms and avoidance of complications

New Onset Murmur or Hamman’s Sign: Mid-systolic click in a Suspected case of Connective Tissue Disorder

We present the case of a 15 y/o previously healthy male who presented to CHMC from an OSH with a 3 day history of shortness of breath, audible clicking noise, and chest discomfort after playing at the batting cages 4 days prior. No history of trauma. He was transferred to CHMC for further evaluation after identification of a pneumothorax on chest CT performed at OSH. With respect to family history, the patient is one of 8 children. Of note, per discussion with family, his older siblings are all tall and have some connective tissue anomalies. Two siblings were noted to have developmental delay. Physical exam was significant for the following: 4/6 mid-systolic click heard best at the left 5th intercostal when lying supine or left lateral decubitus, resolves with sitting up. Positive for 7 of the criteria for connective tissue disorder per the Ghent revised criteria including: wingspan to height ratio was 78 to height 76 (ratio 1.02), Pubic symphysis to floor 45 , pectus excavatum, bilateral positive wrist sign, left thumb sign, hindfoot deformity, skin striae evident on his back and posterior auricular aspect of his neck bilaterally. Initial management included 15L 100% FiO2 per oxy mask. Genetics was consulted with concern for underlying connective tissue disorder. Cardiology was consulted with concern for new onset murmur and an ECHO was performed. Serial imaging of his pneumothorax did not show improvement but as he was clinically stable and asymptomatic, the patient was discharged with follow-up with pediatric surgery scheduled for 2 weeks later. Follow-up with ophthalmology revealed no evidence of myopia or subluxation of the intraocular lens in either eye