Hypertrophic cardiomyopathy in a dog: a systematic diagnostic approach.

A seven-year-old female neutered Parson Russel terrier was referred for syncopal episodes. An electrocardiogram revealed paroxysmal atrial flutter followed by periods of sinus arrest, suggesting sick sinus syndrome. Echocardiography showed severe biventricular wall thickening (hypertrophic cardiomyopathy (HCM) phenotype) with no signs of fixed or dynamic left ventricular outflow tract obstruction. Blood pressure, abdominal ultrasound, serum total thyroxin and thyroid-stimulating hormone, and insulin-like growth factor-1 were all within normal limits. Cardiac troponin I was elevated (1.7 ng/mL, ref<0.07). Serological tests for common infectious diseases were negative. A 24-h Holter confirmed that the syncopal episodes were associated with asystolic pauses (sinus arrest after runs of atrial flutter) ranging between 8.5 and 9.6 s. Right ventricular endomyocardial biopsies (EMB) were performed at the time of pacemaker implantation to assess for storage or infiltrative diseases that mimic HCM in people. Histological analysis of the EMB revealed plurifocal inflammatory infiltrates with macrophages and lymphocytes (CD3+ > 7/mm2) associated with myocyte necrosis, but no evidence of myocyte vacuolisation or infiltrative myocardial disorders. These findings were compatible with myocardial ischaemic injury or acute lymphocytic myocarditis. Molecular analysis of canine cardiotropic viruses were negative. The dog developed refractory congestive heart failure and was euthanised 16 months later. Cardiac post-mortem examination revealed cardiomyocyte hypertrophy and disarray with diffuse interstitial and patchy replacement fibrosis, and small vessel disease, confirming HCM. We described a systemic diagnostic approach to an HCM phenotype in a dog, where a diagnosis of HCM was reached by excluding HCM phenocopies.

Myocarditis and inflammatory bowel diseases: A single-center experience and a systematic literature review.

BACKGROUND: Myocarditis and inflammatory bowel diseases (IBD) are rare conditions, but may coexist. Myocarditis in IBD may be infective, immune-mediated, or due to mesalamine toxicity. A gap of knowledge exists on the clinical features of patients that present myocarditis in association with IBD, especially for endomyocardial biopsy-proven cases. Our aims are: 1) to describe the clinical characteristics of patients with an associated diagnosis of myocarditis and IBD in a single-center hospital, 2) to perform a systematic review of the literature of analogous cases. METHODS: We retrospectively analyzed data of patients followed up at the outpatient Cardio-immunology and Gastroenterology Clinic of Padua University Hospital, to identify those with an associated diagnosis of myocarditis and IBD. In addition, a systematic review of the literature was conducted. We performed a qualitative analysis of the overall study population. RESULTS: The study included 104 patients (21 from our single center cohort, 83 from the literature review). Myocarditis in IBD more frequently affects young (median age 31 years) males (72%), predominantly with infarct-like presentation (58%), within an acute phase of the IBD (67%) and with an overall benign clinical course (87%). Nevertheless, a not negligible quote of patients may present giant cell myocarditis, deserve immunosuppression and have a chronic, or even fatal course. Histological evidence of mesalamine hypersensitivity is scarce and its incidence may be overestimated. CONCLUSIONS: Our study shows that myocarditis in association with IBD, if correctly managed, may have a spontaneous benign course, but predictors of worse prognosis must be promptly recognized.

Arrhythmogenic right ventricular cardiomyopathy. Contribution of cardiac magnetic resonance imaging to the diagnosis.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disease of the heart muscle, mostly due to genetically defective desmosomal proteins. The disease is characterized by fibrofatty replacement leading to ventricular arrhythmias and sudden death in young people and athletes. There is no single clinical gold standard examination for making a definitive diagnosis. The diagnosis is based on multiple parameters, including: (1) global or regional dysfunction and structural alteration of the right ventricle demonstrated on imaging; (2) tissue characterization by endomyocardial biopsy; (3) repolarization and (4) depolarization electrocardiographic abnormalities; (5) arrhythmias; and (6) family history. The so-called phenocopies must be included in the differential diagnosis, always taking into account that there is no single criterion sufficiently specific for a reliable diagnosis of ARVC. Contrast-enhanced cardiac magnetic resonance imaging (CE-CMR) is not yet included in the revised diagnostic criteria, although this is the only imaging modality able to depict fibrosis as late gadolinium enhancement (LGE) deposition. This review analyzes the role of CMR imaging in the diagnostic work-up of ARVC. The lack of specific diagnostic criteria contributes to the under-recognition of the nonclassic variants of ARVC, i.e., dominant or isolated left ventricular disease.

Risk stratification in arrhythmogenic right ventricular cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic cardiomyopathy characterized by myocyte death and fibrofatty replacement mostly in the right ventricle. It is a leading cause of sudden cardiac death (SCD) in individuals under the age of 35 years. The main goal in the treatment of the disease is the prevention of SCD. An implantable cardioverter-defibrillator (ICD) is the only proven life-saving therapeutic option able to improve survival in ARVC patients. This therapy is not free from side effects and it accounts for a relatively high rate of morbidity because of the occurrence of inappropriate ICD interventions and of complications, both at implantation and during the follow-up. In recent years, the approach to ICD implantation has been changing on the basis of new emerging data on risk stratification. The usefulness of ICD implantation for secondary prevention has been definitively proven; the most challenging question is how to treat patients with no history of previous cardiac arrest or hemodynamically unstable ventricular tachycardia (VT). The value of ECG abnormalities, syncope, VT, and right/left ventricular involvement as predictors of SCD has been assessed in different studies with the purpose of better defining risk stratification in ARVC. Nevertheless, in spite of the growing amount of data, primary prevention in ARVC patients remains mostly an individual decision.

Gastrectomía en manga transumbilical con técnica simplificada: técnica y resultados quirúrgicos en 100 pacientes / Simplifi ed transumbilical sleeve gastrectomy: technique and surgical results in 100 patients

Background: The use of transumbilical approach for sleeve gastrectomy has been recently reported, using different technique variations. Aim: To report the technique and surgical results of a transumbilical approach simplified sleeve gastrectomy, using rigid instruments. Material and Methods: Ninety four women and six men, selected by a multidisciplinary team, underwent transumbilical sleeve gastrectomy. The operative technique involved a transumbilical incision, introduction of a SILS® or GelPoint® multiport, and a 5mm metallic accessory trocar laterally in the left flank. Rigid instruments were used in all patients. The greater curvature was dissected from 4-5 cm above the pylorus to the angle of His. Gastric transection was completed with a stapler, and calibrated with a 36 French tube advanced through the pylorus. Hemostasis of the staple line was carried out with metallic clips. A barium swallow was performed in ten randomly chosen patients, confirming the correct tubular shape of the stomach. Results: Body mass index of operated patients ranged from 30 to 43 kg/m². Mean operative time was 56.4 +/- 16.7 minutes. During the early postoperative period, two patients had a hemoperitoneum, one had an antral leak and one had an intestinal perforation. No conversion to conventional laparoscopy or open technique was required. No patient died. The mean length of hospital stay was 2.3 +/- 0.5 days. The cosmetic result was satisfactory for all patients. Conclusions: Transumbilical sleeve gastrectomy is a safe and feasible procedure with the reported technique. The insertion of an accessory 5mm trocar in the left flank simplifies the procedure, allowing the use of rigid instruments.

Introducción: El abordaje transumbilical, ha demostrado ser seguro en diferentes procedimientos. Se han reportado series de casos de gastrectomía en manga transumbilical (GMTU), con diferentes variaciones. Objetivo: Es presentar la técnica y resultados quirúrgicos de una técnica de GMTU simplificada, utilizando instrumental rígido. Material y Métodos: 94 mujeres y seis hombres, fueron sometidos a GMTU, seleccionados por un equipo multidisciplinario. La técnica quirúrgica consiste en una incision transumbilical, introducción de dispositivo SILS® o GelPoint®, y un trocar de 5 mm metálico en el flanco izquierdo. Se utilizó instrumental rígido en todos los pacientes. La disección de la curvatura mayor se realiza desde 4-5 cm proximal al píloro, hasta el pilar izquierdo. La sección gástrica se completa con stapler, calibrando con una sonda de 36 fr transpilórica. Se realiza hemostasia selectiva con clips metálicos. Se realizó estudio baritado a diez pacientes aleatorios, confirmando forma tubular adecuada. Resultados: El rango de IMC preoperatorio fue de 30-43 kg/m². El tiempo operatorio promedio fue de 56,4 +/- 16,7 min. No se requirió conversión a técnica multitrocar o laparotómica. Cuatro pacientes presentaron complicaciones precoces: dos hemoperitoneos, una filtración antral y una enterotomía inadvertida. Se reintervino a dos pacientes. No hubo mortalidad. El tiempo de hospitalización fue de 2,3 +/- 0,5 días. El resultado cosmético fue satisfactorio para todos los pacientes. Conclusión: La GMTU es un procedimiento factible y seguro con la técnica expuesta. La inserción del trocar de 5 mm accesorio, simplifica el procedimiento, permite el uso de instrumental rígido, y lo convierte en un procedimiento reproducible.

Arrhythmogenic right ventricular cardiomyopathy. What is needed for a cure?

There have been major advances in recent years in the clinical setting of arrhythmogenic right ventricular cardiomyopathy, including new diagnostic criteria, a changing spectrum of the disease with even left dominant forms, the role of cardiac magnetic resonance and electroanatomic mapping, the expanding use of genetic screening and the existence of overlapping phenotypes. Moreover, early diagnosis at pre-participation screening with sports disqualification and risk stratification for the indication of ICD have been shown to be life-saving. In addition to traditional therapies targeting arrhythmias and congestive heart failure, an effective treatment of the disease could be based on the discovery of the molecular mechanisms involved in the pathobiology of the disease in order to block the onset and progression of cell death.

Criteria for histopathologic diagnosis of aortic disease consensus statement from the SIAPEC-IAP study group of "cardiovascular pathology" in collaboration with the association for Italian cardiovascular pathology.

Nowadays, the histopathological study of surgical specimens is an essential part of the diagnostic work-up in aortic disease, and not only in characterizing the neoplastic forms. Despite increasing clinico-therapeutic complexity of aortic pathology, the criteria for histopathological diagnosis have not been properly updated over the years, with the result that we find inconsistent terminology and little standardization of diagnostic criteria. In light of this consideration, the SIAPeC-IAP Study Group of "Cardiovascular Pathology", in collaboration with the Association for Italian Cardiovascular Pathology, has created this consensus document, with the aim of defining the features of histopathological substrates in the main non-neoplastic aortopathies (atherosclerotic, "degenerative"/non inflammatory, and inflammatory) and of systematizing diagnostic criteria even for the rare tumours of the aorta and pulmonary artery. The principal aims of the project are defining histopathological diagnostic criteria, standard nomenclature and classification, methodology and reporting of histopathological study and handling of aortic specimens. In addiction, some current issues and new knowledge emerging from basic aortic research are debated, with the aim of promoting a "modern" and up-to-date view of aortic pathology.

Differences and similarities between arrhythmogenic right ventricular cardiomyopathy and athlete's heart adaptations.

BACKGROUND: Regular intensive physical activity is associated with non-pathological changes in cardiac morphology. Differential diagnosis with arrhythmogenic right ventricular cardiomyopathy (ARVC) constitutes a frequent problem, especially in athletes showing ventricular arrhythmias with left bundle branch block morphology. AIM OF THE STUDY: To assess the different clinical and non-invasive instrumental features of the subjects affected by ARVC and by athletes. METHODS: Three groups of subjects (40 ARVC patients, 40 athletes and 40 controls, mean age 27 (9) years) were examined with family and personal history, physical examination, 12-lead ECG, 24-h ECG, signal-averaged ECG and 2-D and Doppler echocardiography. RESULTS: 12-Lead ECG was abnormal in 62% of ARVC patients versus 7.5% of athletes and 2.5% of controls (p<0.0001). Ventricular arrhythmias and late potentials were present in 70% and 55% of ARVC subjects, respectively (vs 5% of athletes and 7.5% of controls, p<0.0001). Left ventricular parietal wall thickness and left ventricular end-diastolic diameters were significantly higher in athletes. Both athletes and ARVC patients presented a right ventricular (RV) enlargement compared with controls. Moreover, RV outflow tract, measured on parasternal long axis and at the level of aortic root, was significantly larger in ARVC patients (33.6 (4.7) mm vs 29.1 (3.4) mm and 35.6 (6.8) mm vs 30.1 (2.9) mm; p<0.0001), and RV fractional shortening and ejection fraction were significantly lower in ARVC patients compared with athletes (40 (7.9)% vs 44 (10)%; p=0.05 and 52.9 (8)% vs 59.9 (4.5)%; p<0.0001). A thickened moderator band was found to be present in similar percentage in ARVC patients and athletes. CONCLUSIONS: An accurate clinical and instrumental non-invasive evaluation including echocardiography as imaging technique allows to distinguish RV alterations typical of ARVC from those detected in athletes as a consequence of intensive physical activity.

Control of the CFTR channel's gates.

Unique among ABC (ATP-binding cassette) protein family members, CFTR (cystic fibrosis transmembrane conductance regulator), also termed ABCC7, encoded by the gene mutated in cystic fibrosis patients, functions as an ion channel. Opening and closing of its anion-selective pore are linked to ATP binding and hydrolysis at CFTR's two NBDs (nucleotide-binding domains), NBD1 and NBD2. Isolated NBDs of prokaryotic ABC proteins form homodimers upon binding ATP, but separate after hydrolysis of the ATP. By combining mutagenesis with single-channel recording and nucleotide photolabelling on intact CFTR molecules, we relate opening and closing of the channel gates to ATP-mediated events in the NBDs. In particular, we demonstrate that two CFTR residues, predicted to lie on opposite sides of its anticipated NBD1-NBD2 heterodimer interface, are energetically coupled when the channels open but are independent of each other in closed channels. This directly links ATP-driven tight dimerization of CFTR's cytoplasmic NBDs to opening of the ion channel in the transmembrane domains. Evolutionary conservation of the energetically coupled residues in a manner that preserves their ability to form a hydrogen bond argues that this molecular mechanism, involving dynamic restructuring of the NBD dimer interface, is shared by all members of the ABC protein superfamily.

Unexpected mechanical bileaflet valve thrombosis in mitral position: what is better to do, re-replacement or thrombolysis.

BACKGROUND AND AIMS: The longevity of the mechanical heart valve prosthesis is an advantage when compared with its biological counterpart, although the former carries a risk of thrombosis depending on valve design, materials and host-related interface; therefore, a patient with a mechanical valve prosthesis, particularly in mitral position, is at risk for systemic thromboembolism even when properly anticoagulated. PATIENTS AND METHODS: We report a case of a 60-year-old woman who underwent a mitral valve replacement with a St. Jude Medical (SJM) standard bileaflet mechanical heart valve. RESULTS: On the twelfth post-operative day a primary thrombosis with blockage of the anterior valve leaflet occurred. CONCLUSIONS: Aware of the risk of recurrent thromboembolism in this special clinical framework and possible cerebral bleeding in case of thrombolysis, we replaced the prosthesis with a new biologic porcine valve, the SJM Biocor.

Arrhythmogenic right ventricular cardiomyopathy: current diagnostic and management strategies.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heart muscle disease of unknown etiology characterized by the peculiar right ventricular (RV) involvement. Distinctive pathologic features are myocardial atrophy and fibro-fatty replacement of the RV free wall, and clinical presentation is usually related to ventricular tachycardias with a left bundle branch block pattern or ventricular fibrillation leading to cardiac arrest, mostly in young people and athletes. Later in the disease evolution, progression and extension of RV muscle disease and left ventricular involvement may result in right or biventricular heart failure. The diagnosis of ARVC may be difficult because of several problems with specificity of ECG abnormalities, different potential etiologies of ventricular arrhythmias with a left bundle branch morphology, assessment of RV structure and function, and interpretation of endomyocardial biopsy findings. Therefore, standardized diagnostic criteria have been proposed by the Study Group on ARVC of the European Society of Cardiology. According to these guidelines, the diagnosis of ARVC is based on the presence of major and minor criteria encompassing electrocardiographic, arrhythmic, morphofunctional, histopathologic, and genetic factors. Since the assessment of sudden death risk in patients with ARVC is still not well established, there are no precise guidelines to determine which patients need to be treated and what is the best management approach. The therapeutic options include beta-blockers, antiarrhythmic drugs, catheter ablation, and implantable cardioverter defibrillator (ICD). The ICD is the most effective safeguard against arrhythmic sudden death. However, its precise role in changing the natural history of ARVC by preventing sudden and nonsudden death needs to be evaluated by a prospective study of a large series of patients. In patients in whom ARVC has progressed to severe RV or biventricular systolic dysfunction with risk of thromboembolic complications, treatment consists of current therapy for heart failure including anticoagulant therapy. In cases of refractory congestive heart failure, patients may become candidates for heart transplantation.

Dispersion of ventricular depolarization-repolarization: a noninvasive marker for risk stratification in arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: We retrospectively investigated the value of clinical and ECG findings as well as QT-QRS dispersion in predicting the risk of sudden death in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). METHODS AND RESULTS: Duration and interlead variability of the QT interval and QRS complex were measured manually from standard ECGs in 20 sudden death victims with ARVC diagnosed at autopsy (group I), in 20 living ARVC patients with sustained ventricular tachycardia (group II), in 20 living ARVC patients with /=40 ms had a sensitivity and specificity of 90% and 77%, respectively; QT dispersion >65 ms, 85% and 75%, respectively; negative T wave beyond V(1), 85% and 42%, respectively; and syncope, 40% and 90%, respectively. CONCLUSIONS: QRS dispersion (>/=40 ms) was the strongest independent predictor of sudden death in ARVC. Syncope, QT dispersion >65 ms, and negative T wave beyond V(1) refined arrhythmic risk stratification in these patients.

Cardiogenic shock due to metastatic cardiac lymphoma: still a diagnostic and therapeutic challenge.

Myocardial involvement by metastatic lymphoma progressively leads to severe contractile impairment and fatal outcome. Correct diagnosis is often late due to misleading presentation signs. We report on a case of extensive cardiac involvement of a T-cell thymic lymphoma in a young woman, necessitating emergent extracorporeal membrane oxygenation (ECMO) circulatory support, with satisfactory hemodynamic recovery and subsequent ECMO weaning. Unfortunately, the following clinical course was rapidly fatal. This case seems to confirm that early aggressive instrumental diagnosis is crucial before severe myocardial impairment can prevent any therapeutic option. Extensive use of transesophageal echocardiographic examination and early endomyocardial biopsy are highly recommended.

Identification of mutations in the cardiac ryanodine receptor gene in families affected with arrhythmogenic right ventricular cardiomyopathy type 2 (ARVD2).

Arrhythmogenic right ventricular dysplasia type 2 (ARVD2, OMIM 600996) is an autosomal dominant cardiomyopathy, characterized by partial degeneration of the myocardium of the right ventricle, electrical instability and sudden death. The disease locus was mapped to chromosome 1q42--q43. We report here on the physical mapping of the critical ARVD2 region, exclusion of two candidate genes (actinin 2 and nidogen), elucidation of the genomic structure of the cardiac ryanodine receptor gene (RYR2) and identification of RYR2 mutations in four independent families. In myocardial cells, the RyR2 protein, activated by Ca(2+), induces the release of calcium from the sarcoplasmic reticulum into the cytosol. RyR2 is the cardiac counterpart of RyR1, the skeletal muscle ryanodine receptor, involved in malignant hyperthermia (MH) susceptibility and in central core disease (CCD). The RyR2 mutations detected in the present study occurred in two highly conserved regions, strictly corresponding to those where mutations causing MH or CCD are clustered in the RYR1 gene. The detection of RyR2 mutations causing ARVD2, reported in this paper, opens the way to pre-symptomatic detection of carriers of the disease in childhood, thus enabling early monitoring and treatment.

Right bundle branch block, right precordial st-segment elevation, and sudden death in young people.

BACKGROUND: Patients with the ECG pattern of right bundle branch block and right precordial ST-segment elevation may experience sudden death in the setting of either arrhythmogenic right ventricular cardiomyopathy (ARVC) or a functional electrical disorder such as Brugada syndrome. METHODS AND RESULTS: Among a series of 273 young (

Is arrhythmogenic right ventricular cardiomyopathy a paediatric problem too?

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heart muscle disease that is often familial, characterized by arrhythmias of right ventricular origin, due to transmural fatty or fibrofatty replacement of atrophic myocardium. ARVC is usually diagnosed in the clinical setting between 20 and 40 years of age. The disease is seldom recognised in infancy or under the age of 10, probably because the clinical expression of the disease is normally postponed to youth and adulthood. This review focuses its attention to the pediatric age, defined as the period of life raging from birth to 18 years. During this span of life, ARVC is not so rare as previously supposed and can be identified by applying the same diagnostic criteria proposed for the adult. Ventricular arrhythmias range from isolated ventricular arrhythmias to sustained ventricular tachycardia and fibrillation. Children and adolescents with ARVC must be carefully evaluated and followed-up especially when a family positive history is present, taking into account the high probability during this life-period that asymptomatic affected patients become symptomatic or that arrhythmias worsen during follow-up. The recent identification of the first defective gene opens new avenues for the early identification of affected subjects even when asymptomatic.

Clinical profile and long-term follow-up of 37 families with arrhythmogenic right ventricular cardiomyopathy.

OBJECTIVES: We sought to define the clinical picture and natural history of familial arrhythmogenic right ventricular cardiomyopathy (ARVC). BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy is a myocardial disease, often familial, clinically characterized by the impending risk of ventricular arrhythmias and sudden death. METHODS: Thirty-seven ARVC families of northeast Italy were studied. Probands had a histologic diagnosis of ARVC, either at autopsy (19 families) or endomyocardial biopsy (18 families). Protocol of the investigation included basal electrocardiogram (ECG), 24-hour ECG, signal-averaged ECG, stress test and two-dimensional Doppler echocardiography. Invasive evaluation was performed when deemed necessary. RESULTS: Of the 365 subjects, 151 (41%) were affected, 157 (43%) were unaffected, 17 (5%) were healthy carriers, and 40 (11%) were uncertain. Mean age at diagnosis was 31+/-13 years. By echocardiography, 64% had mild, 30% had moderate, and 6% had severe form. Forty percent had ventricular arrhythmias, 49 were treated with antiarrhythmic drugs, and two were treated with implantable cardioverter defibrillators. Sport activity was restricted in all. Of the 28 families who underwent linkage analysis, 6 mapped to chromosome 14q23-q24, 4 to 1q42-q43, and 4 to 2q32.1-q32.3. No linkage with known loci was found in four families and 10 had uninformative results. During a follow-up of 8.5+/-4.6 years, one patient died (0.08 patient/year mortality), and 15 developed an overt form of ARVC. CONCLUSIONS: Arrhythmogenic right ventricular cardiomyopathy is a progressive disease appearing during adolescence and early adulthood. Systematic evaluation of family members leads to early identification of ARVC, characterized by a broad clinical spectrum with a favorable outcome. In the setting of positive family history, even minor ECG and echocardiographic abnormalities are diagnostic.