Arrhythmogenic Ventricular Dysplasia Research Articles

Intracardiac thrombosis: frequency, risk factors and place of oral anticoagulants in treatment

This review systematizes the currently known data on intracardiac thrombosis. The main nosology leading to left atrial thrombosis is atrial fibrillation, with up to 90% of all trombi forming in the left atrial appendage. The optimal method to diagnose thrombosis is the transesophageal echocardiography. The detection rate of left atrial appendage thrombosis in early studies ranged from 2.5 to 74.7% and dropped to 1-15.2% in the era of oral anticoagulants. However, there is no basis for performing transesophageal echocardiography as a screening examination for all patients with atrial fibrillation, and the CHA2DS2-VASc clinical scale is the guideline for prescribing and selecting antithrombotic therapy. The article presents data on the possibility of lysis of the left atrial appendage thrombosis against the background of oral anticoagulants therapy, which is of practical importance for patients before cardioversion and pulmonary vein ablation. The results of published studies and observations of patients receiving vitamin К antagonists show that 46.3-85% of thrombi are dissolved. The only prospective study to investigate the possibility of left atrial thrombosis lysis in patients with atrial fibrillation or fluttering while taking direct oral anticoagulants was X-TRA, which studied rivaroxaban therapy and showed thrombi dissolution in 41.5% of patients. The frequency of left ventricular thrombosis in patients with acute coronary syndrome with ST segment elevation in the age of reperfusion therapy is about 6-7%, reaching 19.2% in patients with anterior myocardial infarction and reduction of left ventricular ejection fraction. These recommendations indicate that only vitamin К antagonists may be prescribed in patients with left ventricular thrombosis. However, the results of the COMMANDER HF study showing the potential of rivaroxaban to prevent thromboembolic complications in patients with chronic heart failure have laid the foundation for the use of direct oral anticoagulants in left ventricular thrombosis. At present the study of efficacy and safety of apixaban and rivaroxaban in this category of patients is ongoing, but there are no results at present. In most cases, right ventricular thrombosis is part of the development of a pulmonary embolism, and much less often it accompanies right ventricular arrhythmogenic dysplasia or is associated with implantable devices. Anticoagulants are the basis for the treatment of these patients, and the present guidelines allow for moderate and low risk thromboembolism in patients with pulmonary artery thromboembolism, along with parenteral anticoagulants, prescribing immediate oral anticoagulants, giving preference to Xa-factor antagonists or direct thrombin inhibitors.

A Multimodality Approach to Assessing Factor I Genetic Variants in Atypical Hemolytic Uremic Syndrome

A Multimodality Approach to Assessing Factor I Genetic Variants in Atypical Hemolytic Uremic Syndrome

THE EXPERIENCE OF PEDIATRIC HEART TRANSPLANTATION ON NORTH-WEST OF RUSSIAN FEDERATION

Aim:to estimate early and long-term outcomes in recipients under 18 years old who have been heart transplanted in Almazov National Medical Research Centre.Materials and methods. From April 2011 to September 2017 we performed 5 heart transplantations (HTx) in recipients under 18 years old (female) old) from adults donors. The median of age were 15 years (range 10–16 years), LVEF prior HTx – 17% (10–33%). Causes of heart failure were dilated cardiomyopathy (n = 2), non-compacted myocardium (n = 1), arrhythmogenic ventricular dysplasia (n = 1) and Ebstein’s anomaly (n = 1). They spent in HT waiting list 76 days (12–684 days). One patient underwent biventricular assist device Berlin Heart EXCOR implantation (days on support – 250) as a «bridge» to transplant. Due to coronary angiography (CAG) results 1 patient underwent HTx and CABG simultaneously. All recipients treated by triple-drug therapy (steroids, calcineurin inhibitors, mycophenolate mofetil), induction (thymoglobulin – n = 4, basiliximab – n = 1). We evaluated retrospectively laboratory-instrumental investigations and frequency of complications after HTx.Results.The median of survival after HT was 35,93 months (4,4–73,7 months), all of them are alive. Patients spent in ICU 12 days (4–18 days), but one – 18 days due to posterior reversible encephalopathy syndrome (PRES), tacrolimus was switched to cyclosporine. They required inotropic support during 3 days (3–8 days). In 1 yr after HT TTE results got to normal values, the same as VO2peak signifi cantly improved. According to EMB (n = 48) results there were no clinical signs of rejection, acute cellular rejection (R2) was diagnosed in 12,5% cases. In long-term follow-up there was no signifi cant post transplant complications and comorbidities.Conclusion.Pediatric heart transplantation is an effective treatment of terminal CHF. There was no signifi cant clinical rejection under combined immunosuppressive regimens. All patients recovered and went back to normal life. Physical capacity improved in all recipients.

Uhl’s anomaly: rare but does exist

A 17-year-old boy presented with facial puffiness and swelling in the lower limbs for 6 months and one episode of syncope 15 days earlier. Transthoracic echocardiography showed a dilated right atrium and right ventricle with right ventricular systolic dysfunction. The free wall of the right ventricle was thinned out and devoid of myocardium and trabeculations. Cardiac magnetic resonance imaging showed an extremely dilated thin-walled right ventricle and absence of trabeculations, with no fat signal in the right ventricular wall, in contrast to that seen in arrhythmogenic ventricular dysplasia, which confirmed the diagnosis of Uhl's anomaly.

Partial Anomalous Pulmonary Venous Return as Rare Cause of Right Ventricular Dilation: A Retrospective Analysis.

Partial anomalous pulmonary venous return (PAPVR) is an uncommon cause of right ventricular dilation. It may be difficult to identify and often remains undiagnosed. We reviewed the database of the Cardiac Magnetic Resonance (CMR) Laboratory of Niguarda Hospital, in order to identify the cases of PAPVR between 2008 and 2014. On a total number of 7832 CMR scans, we identified 24 patients with PAPVR (14 male, age 41 ± 18 y) corresponding to 0.31% of the total population. Only 30% of patients had been referred for known or suspected PAPVR, 33% of patients had been referred for suspected right ventricular arrhythmogenic dysplasia and 37% had been referred for other cardiac disease. PAPVR involved mainly the right pulmonary veins (18 patients, 75%) and in 62% of our cases was associated with an atrial septal defect. Eight patients underwent corrective surgery in our institution, which confirmed and successfully repaired the anomalies. PAPVR is a rare congenital cardiac pathology which should be suspected in case of unexplained right chambers enlargement. CMR imaging allows an accurate anatomic and functional definition of this pathology and associated abnormalities. Early correction has an excellent prognosis and prevents long term complications like pulmonary hypertension, right ventricular failure and atrial fibrillation.

Nav1.5 cardiac sodium channels, regulation and clinical implications

<p>Voltage-gated sodium channels constitute a group of membrane<br />proteins widely distributed thought the body. In the heart, there<br />are at least six different isoforms, being the Nav1.5 the most<br />abundant. The channel is composed of an α subunit that is formed<br />by four domains of six segments each, and four much smaller β<br />subunits that provide stability and integrate other channels into<br />the α subunit. The function of the Nav1.5 channel is modulated<br />by intracellular cytoskeleton proteins, extracellular proteins,<br />calcium concentration, free radicals, and medications, among<br />other things. The study of the channel and its alterations has<br />grown thanks to its association with pathogenic conditions such<br />as Long QT syndrome, Brugada syndrome, atrial fibrillation,<br />arrhythmogenic ventricular dysplasia and complications during<br />ischemic processes.</p>

Sudden Cardiac Death

Sudden death accounts for 300,000-400,000 deaths annually in the United States. Most sudden deaths are cardiac, and most sudden cardiac deaths are related to arrhythmias secondary to structural heart disease or primary electrical abnormalities of the heart. The most common structural disease leading to sudden death is ischemic heart disease. Nonischemic cardiomyopathy and other structural abnormalities such as arrhythmogenic ventricular dysplasia and hypertrophic cardiomyopathy may also be causative. Patients without structural disease have a primary electrical abnormality, such as long-QT syndrome or Brugada syndrome. Severe left ventricular systolic dysfunction is the main marker for sudden death in patients with ischemic or nonischemic cardiomyopathy. In other conditions, other markers for structural heart disease and electrical abnormalities need to be considered. It is seen that β-blocker therapy is associated with a reduction in sudden cardiac death across a broad range of disorders. Nevertheless, the implantable cardioverter defibrillator remains the most effective treatment strategy in selected patients.

Arrhythmogenic Ventricular Dysplasia/Cardiomyopathy: Insights from the Rationale of Disease Nomenclature and Clinical Perspectives

“Arrhythmogenic right ventricular dysplasia” (ARVD), a heart muscle disorder characterized by the presence of fibro-fatty tissue and ventricular electrical vulnerability related to sudden death, was first described in 1977 by a French team. Since then, other terms such as “arrhythmogenic right ventricular cardiomyopathy” (ARVC), “arrhythmogenic cardiomyopathy” (AC), “left-dominant arrhythmogenic cardiomyopathy” (LDAC), and “arrhythmogenic left ventricular dysplasia” (ALVD) have been introduced. These changes in nomenclature of the same disease entity are based on different explanations of pathomorphologic patterns. The dysplasia theory claims cardiac growth “maldevelopment” whereas the cardiomyopathy has been seen as an atrophy from acquired injury (myocyte death) and repair (fibrofatty replacement). The other area of divergent opinion is with regards to involvement of both ventricles rather than being an isolated right ventricular anomaly that may result in increased likelihood of diagnosing the concealed form manifesting with pre-dominant left ventricular arrhythmias. Multiple line of evidences support common disease path-ways: Presence of fibro-fatty and superimposed myocarditis, desmosome mutations and malfunc-tion. These compelling data regarding the heart growth, and pathological, clinical, phenotype/ genotype correlates have advanced our understanding of arrhythmogenic ventricular dysplasia/ cardiomyopathy and increased the diagnostic accuracy as well as providing an avenue for future development of new mechanism-based therapies.

Epicardial ablation as a bailout in electrical storm?

Electrical storm (ES) is one of the most challenging clinical scenarios facing electrophysiologists, and in certain settings emergency ablation should be performed. The majority of ES occurs in patients with structural heart disease, predominantly coronary heart disease and nonischemic heart disease like right ventricular arrhythmogenic dysplasia and previous myocarditis as well as other cardiomyopathies. Implantable cardioverter-defibrillators (ICDs) are the first-line therapy in patients with ventricular tachycardia (VT) and structural heart disease. Recurrent VT episodes or ES are major problems in patients who receive an ICD after a spontaneous sustained VT. In addition, in patients with an ICD implanted for primary prevention of sudden cardiac death, 20 % will experience at least one VT episode within 3-5 years after ICD implantation. Catheter ablation has a high success rate in the acute setting in eliminating clinical VT. However, several factors make enodocardial catheter ablation of VT more difficult especially in advanced ischemic heart disease with heart failure and aneurysm. Frequently in nonischemic cardiomyopathies (NICM) there tends to be an epicardial and intramyocardial substrate where the critical VT zone can occasionally be epicardial or intramural in location. In some patients, an epicardial approach should be warranted first together with an endocardial approach or after failure of enodocardial ablation. Currently, the success rates of endocardial ablation in the acute setting are acceptable, but in the long term they are still not well defined. The purpose of this article is to highlight the importance of epicardial ablation as an alternative approach in controlling ES and to confirm the need for highly qualified centers to manage such challenging cases.

Development of the New Zealand cardiac inherited disease registry

Multi-gene testing panels provided by clinical laboratories have become increasingly available and affordable and have been used since 2008 in South Australia. We audited consecutive patients diagnosed with cardiomyopathy or channelopathy and referred to the SA Clinical Genetics Service for genetic testing between 1 January 2008 and 31 December 2013. 66 probands with cardiac channelopathy were identified, 58 with Long QT syndrome (LQTS), 5 with Brugada syndrome, and 3with other disorders. 62 of these probandswere tested. The 60 completed tests identified 28% with pathogenic variants (All LQTS 29%, familial LQTS 43%, sporadic LQTS 20%) and 13% with variants of uncertain significance (VUS). Proband testing in channelopathy enabled cascade testing in 41 patients, 10 for confirmatory and 31 for predictive testing. 94 probandswith cardiomyopathywere identified, 73 with hypertrophic cardiomyopathy (HCM), 10 with dilated cardiomyopathy, 4 with arrhythmogenic ventricular dysplasia, and 7 with other cardiomyopathies. 77 of these probands were tested. The 70 completed tests identified 47% with pathogenic variants (All HCM 46%, familial HCM 74%, sporadic HCM 22%) and 14% with a VUS. Proband testing in cardiomyopathy enabled cascade testing in 24 patients, 3 for confirmatory and 21 for predictive testing. We found that the yield of genetic testing for cardiomyopathies was similar to published rates, but our yield of genetic testing for cardiac channelopathies was lower than published rates. VUS were found in a considerable proportion of patients. In vivo functional data exist for few variants.

Cardiac genetic testing in South Australia 2008-2013

Multi-gene testing panels provided by clinical laboratories have become increasingly available and affordable and have been used since 2008 in South Australia. We audited consecutive patients diagnosed with cardiomyopathy or channelopathy and referred to the SA Clinical Genetics Service for genetic testing between 1 January 2008 and 31 December 2013. 66 probands with cardiac channelopathy were identified, 58 with Long QT syndrome (LQTS), 5 with Brugada syndrome, and 3with other disorders. 62 of these probandswere tested. The 60 completed tests identified 28% with pathogenic variants (All LQTS 29%, familial LQTS 43%, sporadic LQTS 20%) and 13% with variants of uncertain significance (VUS). Proband testing in channelopathy enabled cascade testing in 41 patients, 10 for confirmatory and 31 for predictive testing. 94 probandswith cardiomyopathywere identified, 73 with hypertrophic cardiomyopathy (HCM), 10 with dilated cardiomyopathy, 4 with arrhythmogenic ventricular dysplasia, and 7 with other cardiomyopathies. 77 of these probands were tested. The 70 completed tests identified 47% with pathogenic variants (All HCM 46%, familial HCM 74%, sporadic HCM 22%) and 14% with a VUS. Proband testing in cardiomyopathy enabled cascade testing in 24 patients, 3 for confirmatory and 21 for predictive testing. We found that the yield of genetic testing for cardiomyopathies was similar to published rates, but our yield of genetic testing for cardiac channelopathies was lower than published rates. VUS were found in a considerable proportion of patients. In vivo functional data exist for few variants.

ENG

The role of stimulant designer drug consumption has been investigated in three fatal cases. In Case 1 the fatal outcome can be attributed to the come down phase following their application, as the blood and urine concentration of the designer drugs was low. In the second case arrhythmogenic effect of methylone was added to the right ventricular arrhythmogenic dysplasia of the patient and these two factors could lead to death. The suicide case (Case 3) was probably the consequence of the withdrawal effect of MDPV (methylenedioxypyrovalerone). The aim of this issue was to focus on some questions of forensic importance that arose in three autopsy cases where the consumption of amphetamine-like designer drugs could play a role in the fatal outcome.

Mapeamento epicárdico da taquicardia ventricular sustentada em cardiopatias não isquêmicas

FUNDAMENTO: A complexidade dos circuitos reentrantes relacionados as taquicardias ventriculares diminui os indices de sucesso dos procedimentos de ablacao por radiofrequencia. OBJETIVO: Avaliar se o mapeamento epicardico com multiplos eletrodos realizado simultaneamente com o mapeamento endocardico auxilia na ablacao da taquicardia ventricular (TV) sustentada em pacientes com cardiopatia nao isquemica. METODOS: Vinte e seis pacientes com TV sustentada recorrente, sendo 22 (84,6%) com cardiopatia chagasica cronica, dois (7,7%) com cardiomiopatia dilatada idiopatica e dois (7,7%) portadores de displasia arritmogenica do ventriculo direito, foram submetidos a mapeamento epicardico com dois ou tres microcateteres, com 8 eletrodos cada, simultaneamente ao mapeamento endocardico convencional. Utilizou-se cateter com ponta de 4 mm para ablacao com radiofrequencia (RF) realizada durante a TV induzida. RESULTADOS: Das 33 TVs induzidas, 25 foram mapeadas e 20 tiveram sua origem definida. Onze com origem epicardica e 9 endocardica. A estimulacao ventricular programada nao induziu TV sustentada em 11 (42,0%) dos 26 pacientes apos a ablacao. Eventos como recorrencia da TV e morte ocorreram em 10,0% dos pacientes submetidos a ablacao com sucesso, e em 59,0% dos insucessos, em seguimento ambulatorial medio de 357 ± 208 dias. CONCLUSAO: Circuitos subepicardicos sao frequentes em pacientes com cardiopatia nao isquemica. O mapeamento epicardico com multiplos cateteres realizado simultaneamente com o mapeamento endocardico contribui para a identificacao destes circuitos em um mesmo procedimento.

Idiopathic ventricular tachycardia arising from the right ventricular apex

Idiopathic, focal ventricular tachycardia that originates from the right ventricular apex is presented. Arrhythmogenic ventricular dysplasia needs to be ruling out prior to making this diagnosis. This is a rare entity that can be cured with an ablation and therefore it needs to be considered in the differential diagnosis of idiopathic VTs before implanting a defibrillator.

Spectrum of pathological changes in both ventricles of patients dying suddenly with arrhythmogenic right ventricular dysplasia. Relation of changes to age

To quantify the variation in fibrosis, fat and muscle within the walls of both ventricles and within the different regions of the heart from six patients dying suddenly of arrhythmogenic right ventricular dysplasia (ARVD) aged 20-60 years. Seven heart regions were examined both macroscopically and histologically using the Picro-Sirius red stain. Quantification of fibrosis, fat and muscle was performed in each region and transmural layer using grid counting. There were macroscopic changes in all examined hearts. A higher percentage of fat with less fibrosis and muscle was observed within the right ventricle of the older patients. The left ventricle had more pathology in the older age group. Statistical differences in pathology in the heart were found. Fat predominated in the epicardial layer in the right and left ventricles of all patients, while the interventricular septum was the least affected. In ARVD, the pathology varies with age in both ventricles, fibrosis being the earliest hallmark of disease, with fatty infiltration evolving later. It should be labelled arrhythmogenic ventricular dysplasia because of biventricular involvement. Histopathologists should therefore sample from whole slices of the heart, so that all the changes can be observed.

Left sided arrhythmogenic ventricular dysplasia in siblings

A 32 year old man with no previous medical history suffered a sudden cardiac death. Post mortem examination revealed circumferential fibro-fatty infiltration of the left ventricular myocardium. Histological appearance was characteristic of arrhythmogenic right ventricular dysplasia but unusual for its localisation only to the left ventricle. As a result of this sudden cardiac death the family of the deceased was screened for cardiac disease. A brother of the index case was 36 years old and free of cardiac history and symptoms. Cardiac investigations revealed a functionally and electrically abnormal left ventricle with apparent sparing of the right ventricle. The brothers may have a left sided form of arrhythmogenic ventricular dysplasia and illustrate the importance of screening family members of young victims of sudden cardiac death.

Left and Right Ventricular Dysplasia and Uhl's Anomaly

Myocardial dysplasia involves a quasi-complete or localized absence of myocardial fibers in the right or left ventricle, with corresponding partial or complete filling by fibroadipose tissue. This disorder, in its full form called "Uhl's anomaly", was first described in 1952 as an anomaly of the heart conferring a parchment-like appearance to its walls. Incomplete forms of the disorder fall into the category of right or left arrhythmogenic ventricular dysplasia. Although approximately 50 cases of right ventricular dysplasia have been documented, only two reports concern left ventricular dysplasia. Having encountered the latter anomaly, we first present the case and our observations, and then review the etiology, pathogenesis, clinical aspects, and evolution of this disorder.