Arrythmogenic Right Ventricular Cardiomyopathy Research Articles

La mort subite de l’adulte : les 10 ans du Centre d’Expertise Mort Subite (CEMS) de Paris

The aim of our study was to highlight the epidemiological difference in adult sudden death between males and females. The type of pathologies found in adult victims of sudden death was compared to control cases in order to determine the most significant pathologies involved in sudden death.Among all autopsies performed between 1995 and 2009, 534 adult cases of sudden death and 154 cases who violently died were respectively selected. For each case, a complete autopsy was carried out, including systematic histological examination of all major organs.The sudden death population was composed of 369 males and 165 females. There was no statistical difference regarding age between males and female. Sudden death took place more often at home in women than in men (p < 0.0001). A stressful event was more frequently found in men than in women (p = 0.03). Deaths caused by cardiovascular diseases were more frequent in males than in females, especially Coronary Artery Disease (CAD) (p < 0.0001). Cardiomyopathy was more often the cause of death in women, particularly Arrythmogenic Right Ventricular Cardiomyopathy (ARVC). Cardiac pathologies were found in 45% of the control cases. CAD and ARVC were statistically more frequent in the sudden death group than in the control group.According to our study, profile of sudden death is different between males and females. Those data seem to be important for clinicians involved in prevention programs of sudden death, as they can adapt their screening according to the gender.

P718 Unexpected finding during follow up for a suspected arrythmogenic right ventricular cardiomyopathy (ARVC)

Abstract Interatrial communication is the most common congenital defect found in adulthood, being the most common ostium secundum variety (70-80%). Superior and inferior sinus venosus defects are less usual, found in the 5-10% of cases of interatrial communication and frequently associated with anomalous pulmonary venous return (APVR). These defects are located near the junction of the superior (5%) or inferior (&amp;lt;1%) vena cava with the right atrium, which makes them difficult to diagnose by transthoracic ecocardiography (TTE). Case description: A 44-year-old man who is being followed up in our electrophysiology consulting with suspicion of ARVC (suggestive CMR with no gene found) after an episode of ventricular tachycardia (VT) 11 years ago. Asymptomatic since then under treatment with atenolol, except for an episode of chest pain that required a coronary computed tomography which described an image compatible with a patent foramen ovale and normal coronary arteries. During the follow-up a cardio magnetic resonance (CMR) is performed which showed a severely dilated right ventricle with diskinetic areas, no volume changes since last CMR (5 years ago) and preserved ejection fraction. A small interatrial communication located infero-posteriorly in the septum drawed our attention. Estimated QP/QS was 1.4. After this finding, we reviewed the CT made 4 years ago, where a flow from the left atrium to the right atrium could be seen. We decided to ask for both a transthoracic echocardiography (TTE) and a transesophageal echocardiography (TEE). TTE showed normal left ventricle, a dilated right ventricle with preserved function, no valvulopathies and normal pulmonary pressure. Shunt test with agitated saline was slightly positive after Valsalva maneuver, and QP/QS was again 1.4. TTE showed a small interatrial communication measuring 1.9x0.8cm, next to inferior vena cava`s drainage. Since right ventricle dilation could be due both to the atrial septal defect (ASD) and to the dysplasia, the case was discussed in the heart team, and as the defect was small, QP/QS was 1.4 and pulmonary pressure was normal we adopted a conservative approach. Inferior sinus venosus defects are one of the least common atrial septal defects. They are located in the atrial septum immediately above the orifice of the inferior vena cava and are often associated with partial anomalous connection of the right pulmonary veins. This location makes it difficult to see by means of a common TTE or TEE, and usually as in our case multimodal approach can be very helpful. Usually patients with this kind of atrial septal defect (ASD), signs of significant shunt (right ventricular volume overload, QP/QS≥1.5) and systolic PA pressure less than 50% of systemic pressure (with pulmonary vascular resistance less than one third of the systemic vascular resistance) are suggested for surgery. In this case the possibility of two pathologies overlapping makes it challenging for diagnosis and treatment. Abstract P718 Figure. Multimodal imaging for diagnosis.

Familial cardiomyopathy in patients affected by acute myocarditis is strongly associated to DSP gene mutations

The link between acute myocarditis (AM) and familial cardiomyopathies (CM) remains unclear. To assess the clinical significance of AM in families with CM. We describe the pedigree of 6 families with at least one case of AM and a familial history of CM or sudden death (SD). AM was defined as an infarct-like clinical presentation with normal coronary arteries and myocardial inflammation (MI) documented by cardiac magnetic resonance (CMR), or as an autopsy proven AM. In family 1 to 5, genetic testing was triggered by the association of a documented case of AM with an index case of CM or early SD. In this setting, all genetic testing revealed a mutation in the desmoplakin (DSP) gene. In family 1, patient II.1 (15 y.o) was diagnosed with AM 6 months after his 12 y.o sister's SD. In family 2, patient II.4 (17 y.o) was diagnosed with AM. His mother had a DCM, with a CMR revealing the presence of MI. In family 3, patient IV.3 (22 y.o) died suddenly from an AM, attested by post-mortem autopsy. Her aunt had a DCM. In family 4, patient II.4 (41 y.o) had an AM, progressing toward a DCM. Her mother had died suddenly at the age of 39, and her niece had a DCM. In family 5, patient V.16 (9 y.o) presented 4 recurrent episodes of AM. Her cousin's mother had a DCM. In family 6, patient IV.3 had 3 episodes of AM, his father had previously been diagnosed with an arrythmogenic right ventricular cardiomyopathy (ARVC) with a desmoglein 2 (DSG2) mutation ( Table 1 , Fig 1). AM is strongly associated to desmosomal mutations when a familial history of cardiomyopathy is present, particularly in DSP gene. In these families, DCM phenotype and SD are frequent, and a notable proportion of isolated LGE suggestive of myocardial fibrosis is present in asymptomatic relatives. These results highlight the need for a comprehensive familial screening in case of AM.

2423Familial cardiomyopathy in patients affected by acute myocarditis is strongly associated to DSP gene mutations

Abstract Background The link between acute myocarditis (AM) and familial cardiomyopathy remains unclear. Purpose To assess the clinical significance of AM in families with cardiomyopathy. Methods and results We describe the pedigree of 6 families with at least one familial case of AM and a familial history of cardiomyopathy or sudden death (SD). AM was defined as an infarct-like clinical presentation with normal coronary arteries and myocardial inflammation (MI) documented by cardiac magnetic resonance (CMR), or as an autopsy proven AM. Detailed familial pedigrees are shown in the picture. In family 1 to 5, genetic testing was triggered by the association of a documented case of AM with an index case of cardiomyopathy or early SD. In this setting, all genetic testing revealed a mutation in the desmoplakin (DSP) gene. In family 1, patient II.1 (15 y.o) was diagnosed with AM, 6 months after his sister died suddenly at the age of 12. In family 2, patient II.4 (17 y.o) was diagnosed with AM. His mother had a DCM, with a CMR revealing the presence of MI. In family 3, patient IV.3 (22 y.o) died suddenly from an AM, attested by post-mortem autopsy. Her aunt had a DCM. In family 4, patient II.4 (41 y.o) had an AM, progressing toward a DCM. Her mother had died suddenly at the age of 39, and her niece had a DCM. In family 5, patient V.16 (9 y.o) presented 4 recurrent episodes of AM. Her cousin's mother had a DCM. In family 6, patient IV.3 had 3 episodes of AM, his father had previously been diagnosed with an arrythmogenic right ventricular cardiomyopathy (ARVC) with a desmoglein 2 (DSG2) mutation. Table shows detailed genotype-phenotype relationship in all mutation carriers screened in the 6 families. Phenotypes observed in mutation carriers Mutation DCM ARVC AM Isolated LGE (no cardiomyopathy, no AM) Family 1 (n=3) DSP 0 0 1 1 Family 2 (n=3) DSP 1 0 1 0 Family 3 (n=11) DSP 5 0 1 0 Family 4 (n=3) DSP 2 0 1 0 Family 5 (n=7) DSP 2 0 1 3 Family 6 (n=5) DSG2 0 1 1 1 Family Pedigrees Conclusion AM is strongly associated to desmosomal mutations when a familial history of cardiomyopathy is present, particularly in DSP gene. In these families, DCM phenotype and SD are frequent, and a notable proportion of isolated LGE suggestive of myocardial fibrosis is present in asymptomatic relatives. These results highlight the need for a comprehensive familial screening in case of AM.

An Update on Pediatric Cardiomyopathy.

This review summarizes the clinical characteristics and updated outcomes of primary pediatric cardiomyopathies including dilated (DCM), hypertrophic (HCM), and restrictive cardiomyopathy (RCM), and briefly discusses left ventricular non-compaction (LVNC) and arrhythmogenic cardiomyopathy (ACM), primarily arrythmogenic right ventricular cardiomyopathy (ARVC). Pediatric cardiomyopathies are diseases of the heart muscle with an estimated annual incidence of 1.1-1.5 cases per 100,000. They are progressive in nature and are frequently caused by a genetic mutation causing a structural abnormality in the myocyte. Dilated cardiomyopathy, characterized by left ventricular dilation and systolic dysfunction with normal left ventricular wall thickness, accounts for about 50-60% of all pediatric cardiomyopathy cases. This is followed by hypertrophic cardiomyopathy accounting for about 40%, characterized by abnormally thickened myocardium in the absence of another cause of hypertrophy with non-dilated left ventricle. Left ventricular non-compaction and restrictive cardiomyopathy each account for about 5% of the cases. Genetic mutations play a dominant role in the development of pediatric cardiomyopathies. While treatment for congestive heart failure and arrhythmias alleviates symptoms, it has not been shown to reduce the risk of sudden death. The 5-year transplant-free survival of DCM, HCM, RCM, and LVNC are 50%, 90%, 30%, and 60% respectively. Pediatric cardiomyopathies while not common they are a significant cause of morbidity and mortality in afflicted children. Dilated forms are the most common followed by hypertrophic, left ventricular non-compaction, and restrictive cardiomyopathies. Arrhythmogenic cardiomyopathies tend to be diagnosed later in the teenage years. Treatment typically follows adult recommendations for which there is significantly more data on treatment benefits, although the indications for ICD placement in children remain even less clear, other than for secondary prevention.

DIAGNOSTIC YIELD OF CARDIOVASCULAR MAGNETIC RESONANCE (CMR) SCREENING FOR ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY (ARVC) STRATIFIED BY BASELINE ECHOCARDIOGRAPHY FINDINGS OF THE RIGHT VENTRICLE

Arrythmogenic right ventricular cardiomyopathy (ARVC) is a rare inherited cardiomyopathy but an important cause of sudden death. Cardiovascular Magnetic Resonance (CMR) imaging is considered the gold-standard for exclusion of its structural phenotype, however, limited availability poses challenge in many communities. We aimed to study the relative diagnostic yield of CMR in patients with versus without abnormal right ventricular (RV) findings by routine 2D echocardiography. 447 patients referred for the screening of ARVC between February 2015 and December 2017 were identified from the Cardiovascular Imaging Registry of Calgary (CIROC). A standardized CMR imaging and analysis protocol was used to assess chamber volumes, function and architectural changes in accordance with the 2010 modified Task Force Criteria (mTFC). All patients having echocardiographic imaging within 12 months prior to CMR were identified and a blinded review of reports was performed. A final clinical diagnosis was derived based on the assimilation of all clinical information, and was classified as meeting or not meeting mTFC for ARVC. Of 447 enrolled patients, 387 (76.6%) had echocardiogram performed and were studied. A final diagnosis of definite ARVC was established in nine (2.3%) patients. Echocardiography reported no RV abnormalities in 283 (73.1%) patients (Group A), while 104 patients (26.9%) had at least one abnormal finding (Group B), defined as; reduced RV function, regional RV wall motion abnormality, global or focal dilatation, aneurysm or “hyper-reflective” trabeculations. In Group A, the yield of any mTFC by CMR was 4 (1.4%) with three patients having a minor and one having a major criterion. Two Group A patients (0.7%) ultimately received a diagnosis of ARVC, neither showing any imaging-based abnormalities. In Group B, the yield of any mTFC by CMR was 13 (12.5%) with nine subjects having a major and 4 having a minor criterion. Seven Group B patients (6.7%) were eventually diagnosed with ARVC, 5 (4.8%) meeting a CMR-based mTFC and 2 (1.9%) with normal CMR. Overall, the sensitivity and specificity of CMR for ARVC was 0% and 98.6% in Group A, and 71.4% and 91.7% in Group B. Among patients without RV abnormality by echocardiography referred to CMR for suspected ARVC, the yield of a CMR-based mTFC was low (1.4%) and did not lead to a diagnosis of ARVC in any subject. In contrast, patients with an RV abnormality had a CMR-based yield of 12.5%, leading to a diagnosis of ARVC in 4.8% of patients.

0211 : Implications of baselines 2010 task force criterias on ventricular arrhythmias in ARVC

Arrythmogenic right ventricular cardiomyopathy (ARVC) is an autosomic dominant disease with a variable penetrance. Based on 2010 task force criteria, baselines characteristics of patients referred from 3 French centers were analyzed to identified risk factors for ventricular arrhythmias. All patients with a diagnosis of ARVC referred from 3 academic French centers between 2006 and 2014 were included. The diagnosis was based on the 2010 Task Force. Occurrence of sustained ventricular arrhythmias and date of last alive status were collected from each center. The population consisted in 259 patients (171 males, sex ratio 1.9) with a mean age at diagnosis of 40+/-17 years. The VA group is composed of 61 patients (23.5%) who experienced at least 1.9 VT episodes. An ICD was implanted in 59% of them. Mean follow-up was 4.0 years in “no VA group” and 7.5 years in “VA group” (p=0.0003). Occurrence of syncope (OR=2.26, 95%CI [0.99-5.0], p=0.03) or VA (OR=3.1, 95%CI[1.8-5.2], p<0.0001) and sustained or non-sustained VA during exercise testing were associated (OR=4.2, 95%CI [0.90-19.5], p=0.03) with VA during follow-up. We failed to identify any ECG parameter related to the occurrence of VA. Dilated right ventricular (RV) was significantly associated with VA during follow-up (OR = 3.6, 95%CI [1.36;9.65], p=0.005). Severe RV dysfunction was more often identified (10% vs 3%, p=0.06) in the “VA group” in echocardiography. By MRI, RVEF was significantly lower in “VA group” (34.6% vs 42.1%, p=0.03) but RV end diastolic volume and presence of akinesia or dyskinesia were not significantly different between two groups. Genetic screening is on-going for all patients. Genetic screening will be performed using HaloPlex™ Target Enrichment System (Agilent Technologies) which allow the sequencing of 163 genes previously reported as involved in cardiac arrhythmias, conduction defect and cardiomyopathies . Occurrence of syncope and VA at baseline or during exercise test are associated with occurrence of VA during follow-up. RV abnormalities on echocardiography and MRI are significantly associated with VT.

Sudden adult death: An autopsy series of 534 cases with gender and control comparison

The aim of our study was to highlight the epidemiological difference in adult sudden death between males and females. The type of pathologies found in adult victims of sudden death was compared to control cases in order to determine the most significant pathologies involved in sudden death.Among all autopsies performed between 1995 and 2009, 534 adult cases of sudden death and 154 cases who violently died were respectively selected. For each case, a complete autopsy was carried out, including systematic histological examination of all major organs.The sudden death population was composed of 369 males and 165 females. There was no statistical difference regarding age between males and female. Sudden death took place more often at home in women than in men (p < 0.0001). A stressful event was more frequently found in men than in women (p = 0.03). Deaths caused by cardiovascular diseases were more frequent in males than in females, especially Coronary Artery Disease (CAD) (p < 0.0001). Cardiomyopathy was more often the cause of death in women, particularly Arrythmogenic Right Ventricular Cardiomyopathy (ARVC). Cardiac pathologies were found in 45% of the control cases. CAD and ARVC were statistically more frequent in the sudden death group than in the control group.According to our study, profile of sudden death is different between males and females. Those data seem to be important for clinicians involved in prevention programs of sudden death, as they can adapt their screening according to the gender.

Effect of the 2010 task force criteria on reclassification of cardiac MRI criteria for ARVC

Background We sought to evaluate the effect of application of the revised 2010 Task Force Criteria (TFC) on the prevalence of major and minor MRI (Magnetic Resonance Imaging) criteria for Arrythmogenic Right Ventricular Cardiomyopathy (ARVC) versus application of the original 1994 TFC. We also assessed the utility of MRI to identify alternative diagnoses for patients referred for ARVC evaluation.

Arrhythmogenic right ventricular cardiomyopathy as cause of severe heart failure leading to heart transplantation

Purpose: Arrythmogenic right ventricular cardiomyopathy (ARVC) is predominantly known as a cause of sudden death and ventricular arrhythmias in the young, whereas the relationship between ARVC and heart failure (HF) has been scarcely investigated. We aimed this study to evaluate prevalence, incidence, pathophysiology and morphologic basis of ARVC leading to severe HF. Methods: We retrospectively analyzed 60 patients with ARVC evaluated at a single referral centre. We compared the clinical, electrocardiographic, hemodynamic and echocardiographic findings of ARVC patients with/without severe HF (NYHA III-IV) at first evaluation or during follow up. We also analyzed the histopathological findings of the explanted hearts of patients who underwent heart transplantation. Results: Severe HF was present in 10 patients at presentation (prevalence=16%) and occurred in other 9 during a median follow up of 68 months (IQR 24-127; incidence=2.3% person-years). Fourteen patients (23%) required heart transplantation and 40 patients (66%) underwent ICD implantation. Patients with advanced HF were younger at symptom onset (47±16 versus 37±12 years, p=0.01) and more often had epsilon waves in the right precordial leads (53% versus 8%, p=0.001) and low voltages in the peripheral leads (46% versus 16%, p=0.05); right ventricle (RV) was larger and more hypokinetic at echocardiography (RVOT 41±6 versus 37±6 mm, p=0.02; RV end diastolic internal diameter 35±12 versus 28±8 mm, p=0.01; fractional shortening area 24%±8 versus 31%±11, p= 0.016). Interestingly, left ventricle (LV) was slightly more dilated (75±30 ml/m2 versus 60±20, p= 0.02) and globally hypokinetic (LV Ejection Fraction =41%±16 versus 57%±12, p= 0.001). The hemodynamic profile of patients who underwent cardiac transplantation was characterized by low cardiac index (1.8±0.2 l//min/m2) with normal or nearly normal capillary wedge and pulmonary pressure (12±8 mmHg and 26±10 mmHg). A detailed histological analysis of the explanted hearts showed extensive (>60% of the surface) fibro-fatty infiltration of the right ventricle and isolated or confluent areas of LV fibrosis. In 4 patients (28%) flogistic infiltrations were also evident. Conclusions: In ARVC, HF can be the only symptom at presentation and leads to heart transplantation in a relevant subset of patients. Patients who develop advanced HF are younger, have more severe right ventricular involvement associated with slight dilation and global hypokinesia of the LV, due to fibrotic infiltration.

Impact of cardiac magnetic resonance imaging on cardiac device and surgical therapy: a prospective study

Cardiac magnetic resonance (CMR) imaging may allow more appropriate selection of patients for cardiac device implantation and/or cardiac surgery. In this prospective observational study we evaluated the impact of CMR imaging on cardiac device and surgical therapy. All CMR examinations performed in a single centre over a 2 year period were prospectively recorded in a dedicated database under 4 clinical pathways [cardiomyopathy, viability, tumour/mass and arrythmogenic right ventricular cardiomyopathy (ARVC)]. Baseline data entered included planned cardiac device implantation and/or cardiac surgical intervention. Patients were contacted 6 months following CMR to evaluate the impact of CMR on planned therapy. Cost savings due to CMR were calculated as the number of surgical or device procedures averted following CMR scanning multiplied by their respective cost weights. Of 732 CMR examinations performed, the clinical pathway was cardiomyopathy in 488 (67 %), ARVC in 118 (16 %), viability in 92 (12 %) and tumour/mass in 34 (5 %). Six month follow-up was available in 666/732 patients. Following CMR, 56/150 (37 %) of patients with an initial plan for device implantation or cardiac surgery, did not undergo the planned intervention (P < 0.001, one-sample exact binomial test). Of 516 patients without an initial device or surgical plan, 33 (6 %) CMR resulted in device implantation or cardiac surgery (P < 0.001, Chi squared). Overall, the estimated saving due to CMR-guided management changes was AUD$737,270. CMR has a significant impact on patient management and offers potential cost savings with respect to selection of device and surgical therapy for cardiac disease.

Spectrum of congenital myopathies: A single centre experience

Congenital myopathies (CMs) are rare and they are clinically and genetically heterogeneous. Muscle biopsy is characterized by structural abnormality that is diagnostic. There are few studies from India. This is a retrospective study of 12 years. The demographic data, clinical features and laboratory data of patients diagnosed as CMs on muscle biopsy were retrieved from medical records. The slides were reviewed for morphological and structural abnormalities using the following stains hematoxylin and eosin, modified Gomori trichrome, masson trichrome, periodic acid schiff, adenosine triphosphatase preincubated at pH 9.4, 4.6 and 4.3, nicotinamide adenine dinucleotide tetrazolium reductase, succinic dehydrogenase and cytochrome c oxidase. Immunohistochemistry was performed with dystrophin, sarcoglycans and desmin wherever necessary. There were 50 patients with CMs: Centronuclear myopathy (23), myotubular myopathy (3) and central core disease (CCD) (8), nemaline myopathy (5), congenital fiber type proportion (10) and desmin related myopathy with arrythmogenic right ventricular cardiomyopathy (ARVD) (1). Of the 50 patients, 30 (60%) presented in the first decade of life. Proximal muscle weakness and hypotonia were the common presenting features. Type 1 atrophy and predominance were seen in most cases on muscle biopsy. CCD had one patient with high creatine phosphokinase levels, biopsy in one patient showed both rods and cores, in the other limb girdle muscular dystrophy like picture and one biopsy showed uniform type 1 fibers. There was one desmin related myopathy with ARVD, who had cardiac transplantation and both skeletal and cardiac muscle showed characteristic rimmed vacuoles and inclusions positive for desmin. CMs are rare and the diagnosis can only be established on muscle biopsy. Defining the specific CMs helps the clinician in counseling the patient and family.

446 Magnetic resonance imaging in the diagnosis of childhood arrhythmogenic right ventricular cardiomyopathy

Arrythmogenic right ventricular cardiomyopathy (ARVC) is characterized by right ventricular (RV) dysfunction and fibrofatty replacement of the myocardium. In adults, magnetic resonance imaging (MRI) has been shown to be a useful non-invasive tool in the diagnosis of ARVC. We sought to evaluate the ability of qualitative and quantitative MRI parameters to predict a diagnosis of ARVC. All cardiac MRI studies performed between 2005 and 2009 in 142 pediatric patients (mean age 11.7 ± 4.0 years) referred for imaging evaluation of suspected ARVC were reviewed. Comparisons were made between MRI findings in patients with and those without ARVC. Of all patients referred for MRI 47% had a positive family history, 38% had cardiac symptoms, 3% had had a sudden cardiac arrest, and 35% had ventricular arrhythmias. 47 subjects met the Task Force Criteria for ARVC, without using MRI criteria. Wall motion abnormalities (WMA) were found in 28/47 (60%) ARVC subjects compared to 25/96 (26%) subjects without ARVC (P = 0.0002). Of subjects with ARVC, 26 (55%) had severe WMA and 13 (28%) had moderate WMA. The Severity of WMA correlated with the probability of ARVC (P = 0.002). The specificity and sensitivity of WMA were 67% and 74%, respectively. RV end-diastolic volume was a strong predictor of ARVC with an dds ratio of 1.03/ml (P = 0.002). Abnormal trabeculations, thinning and outflow tract dilation of the RV were all very specific (>90%) but not very sensitive for ARVC (<30%). Fatty infiltration and fibrosis were identified in only 1 and 3 ARVC patients, respectively. RV regional WMA and RV size contribute to a diagnosis of ARVC, but must be integrated into the context of other MRI findings. These include RV aneurysm, trabeculation, accordion sign and wall thinning. They have high specificity and can improve the post-test probability of a diagnosis, although not part of the Task Force Criteria.

124 Peak systolic 2D strain may help to characterize arrhytmogenic right ventricular cardiomyopathy

Arrythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disease characterized by progressive fibrofatty replacement of the right ventricle (RV). The diagnosis of ARVC remains a challenge for clinicians. We hypothesized that 2D strain imaging helps to differentiate ARVC from normals. 20 patients meeting both the Task Force and cardiac MRI criteria for ARVC were compared to 10 age-matched controls. From the apical-4 chamber view, we measured the end-diastolic RV area, the peak systolic S tissue velocity at the tricuspid level. A 2D strain region of interest including the RV free wall and the septum (occasionally diseased in ARVC) was manually traced, from which the averaged peak systolic 2D strain along 6 segments was calculated. Pulmonary systolic pressure as well as the systolic right atrial area were measured as surrogate for RV loading conditions. Overall, patients with ARVC had both larger right atrial and ventricular area (p < 0.03 and p < 0.02, respectively), compared to controls while pulmonary systolic pressure were similar in both groups (p = 0.40). Peak systolic 2D strain was statistically deteriorated in ARCV patients (13 ± 6 vs. 23 ± 4% in normals, p < 0.001) so as peak systolic S tissue velocity (8 ± 3 vs. 12 ± 4 in normals, p < 0.005). From the ROC analysis, a peak systolic 2D strain of 19.7% had a sensitivity and specificity of 82% and 86% (AUC = 90) while the peak systolic tissue velocity of 12 cm/s gave a sensitivity of 83% and a specificity of 71% (AUC = 79). Peak systolic 2D strain is deteriorated in ARVC patients and may help to characterize arrythmogenic right ventricular cardiomyopathy.

Linkage analysis of three families with arrythmogenic right ventricular cardiomyopathy in India

BACKGROUND:Arrythmogenic Right Ventricular Cardiomyopathy (ARVC) is a primary myocardial disorder morphologically characterized by subtle to severe replacement of the right ventricular myocardium by fatty and fibrous tissue. ARVC is known to be highly prevalent in European population with recent reports implicating it to be a major cause of sudden death in young individuals even from American and Asian population.AIM:To implicate or exclude TMEM43 (ARVC-5), DSP(ARVC-8) genes and the yet to be identified gene at ARVC-6 locus in the pathogenesis in three families affected with ARVC from India.MATERIALS AND METHODS:Three families comprising of 42 affected/unaffected members were included in the study. Three microsatellite markers, D3S3613 (ARVC5) D10S1664 (ARVC6), D6S309 (ARVC8) were genotyped by PCR-based native PAGE. Two-point Linkage analysis was performed using LINKAGE program version 5.2RESULTS AND DISCUSSION:LOD scores from linkage analysis for the microsatellite marker D10S1664 (ARVC-6) in families KS and REV have shown positive value hinting the involvement of this locus in the etiology of ARVC, while linkage analysis in the SB family ruled out involvement of DSP, TMEM43 and ARVC-6, as negative LOD scores were obtained with all three loci. Therefore, linkage analysis carried out in the present study indicates that ARVC-6 (cumulative LOD score is equal to plus 1.203376 at θ is equal to 0.05) could be the locus harboring the mutated gene in two out of three families.

The effects of development control on the growth of rapidly expanding cities

The aim of our study was to highlight the epidemiological difference in adult sudden death between males and females. The type of pathologies found in adult victims of sudden death was compared to control cases in order to determine the most significant pathologies involved in sudden death.Among all autopsies performed between 1995 and 2009, 534 adult cases of sudden death and 154 cases who violently died were respectively selected. For each case, a complete autopsy was carried out, including systematic histological examination of all major organs.The sudden death population was composed of 369 males and 165 females. There was no statistical difference regarding age between males and female. Sudden death took place more often at home in women than in men (p < 0.0001). A stressful event was more frequently found in men than in women (p = 0.03). Deaths caused by cardiovascular diseases were more frequent in males than in females, especially Coronary Artery Disease (CAD) (p < 0.0001). Cardiomyopathy was more often the cause of death in women, particularly Arrythmogenic Right Ventricular Cardiomyopathy (ARVC). Cardiac pathologies were found in 45% of the control cases. CAD and ARVC were statistically more frequent in the sudden death group than in the control group.According to our study, profile of sudden death is different between males and females. Those data seem to be important for clinicians involved in prevention programs of sudden death, as they can adapt their screening according to the gender.