Extensive Cardiac Involvement Research Articles

1041 ELECTROCARDIOGRAPHIC HETEROGENEITY OF PATIENTS WITH VARIANT TRANSTHYRETIN AMYLOID CARDIOMYOPATHY: GENOTYPE PHENOTYPE CORRELATIONS

Abstract Transthyretin (TTR) amyloid cardiomyopathy due to mutation on TTR gene (vATTR) has extremely different features according to the type of mutation, ranging from a mild to an extensive cardiac involvement. Data about electrocardiographic findings (ECG) in vATTR are limited and not informative of genotype correlation. Aim of this study is to analyze ECG characteristics and their correlation to clinical and echocardiographic aspects in patients with vATTR cardiomyopathy, focusing on different TTR mutations. This is a multicentric, retrospective, observational study performed in six Italian referral centres for cardiac amyloidosis. We divided patients in two groups, according to the previously described phenotypic manifestations of the TTR mutation. Of 64 patients with vATTR cardiomyopathy, 23 (36%) had prevalent cardiac (PC) TTR mutations and 41 (64%) patients had a prevalent neurological (PN) TTR mutations. Patients with PC mutations were more frequently males and older, with advanced NAC staging. At baseline ECG, atrial fibrillation was more common in patients with PC, while pacemaker induced rhythm in those with PN mutations. Prevalence of atrioventricular and intraventricular blocks, pseudonecrosis pattern and low voltages were not significantly different in both groups. PQ and QRS durations were longer and voltage to mass ratio was lower in PC mutations. Different TTR mutations tend to have distinctive ECG features. The standard ECG in vATTR is extremely heterogeneous and the specific mutations are associated with distinct instrumental and clinical features. The differences between PN and PC vATTR are only partially explained by the different degree of cardiac infiltration.

Abstract 14956: Extensive Cardiac Involvement in Laminopathies Diagnosed in Pediatric-Aged Patients: A Single Center Study

Introduction: Lamin A/C ( LMNA ) gene mutations result in a heterogeneous group of inherited conditions termed laminopathies. Cardiac manifestations of laminopathies include atrial and ventricular arrhythmias, atrioventricular conduction disorders, and cardiomyopathy, with or without skeletal muscle involvement. Because this disease is rare and typically presents in adulthood, pediatric data is limited. Methods: We identified patients < 18 years with genetically confirmed mutations in LMNA followed at our center between 2003 and 2021. Clinical phenotypes along with cardiac test results were retrospectively catalogued. Results: We identified 12 patients with a median age of 5 years at diagnosis (IQR 4-11 years) with a LMNA mutation. Nine (75%) patients were male and 10 (83%) had associated skeletal muscle involvement. Of the 12 patients, 10 (83%) developed cardiac manifestations over a median follow up period of 111 months (IQR 91-116 months). Seven patients (58%) had documented arrhythmias (AV block, ventricular/atrial tachycardias) and 3 (25%) underwent pacemaker and/or implantable cardiac defibrillator placement. Three (25%) patients were diagnosed with cardiomyopathy with 1 (8%) requiring a ventricular assist device and 1 (8%) requiring continuous intravenous inotropes and subsequent transplant. Three (25%) patients died during the study period, one awaiting transplant, one from complications post-transplant, and one from non-cardiac causes. Conclusions: Cardiac involvement, specifically cardiomyopathy and progressive conduction system abnormalities, were common in pediatric patients with LMNA mutations. Early genetic diagnosis of laminopathies followed by frequent surveillance for dysrhythmia and dysfunction is necessary for more timely initiation of advanced cardiac therapies to prevent adverse events. More comprehensive phenotype-genotype correlation is strongly needed.

A Frequent Observation of Wolff-Parkinson-White Syndrome and Fasciculoventricular Pathways in Patients With Danon Disease.

Danon disease is typically associated with cardiomyopathy and ventricular pre-excitation. The study aimed to characterize the clinical profile of Danon disease, analyze electrocardiographic (ECG) and electrophysiologic features, and investigate their association with Wolff-Parkinson-White (WPW) syndrome and fasciculoventricular pathways (FVPs).Methods and Results:Clinical course, family history, ECG and electrophysiological data were collected from 16 patients with Danon disease. Over 0.4-8 years of follow up, 1 female patient died suddenly, and 5 male patients died of progressive heart failure by age 13-20 years. Family history analysis revealed that 3 mothers experienced hospitalization or death for heart failure at age 28-41 years. There was 100% penetrance for ECG abnormalities in 13 patients with original ECGs. Short PR intervals and delta waves were present in 9 and 8 patients, respectively. There were significant age-associated increases in the QRS complex width (r=0.556, P=0.048) and the number of leads with notched QRS (r=0.575, P=0.04). Four patients who underwent electrophysiological studies all had FVPs, and 2 of them still had left-side atrioventricular pathways. Danon disease causes a malignant clinical course characterized by early death caused by heart failure in both genders and progressive ECG changes as patients age. The pre-excited ECG pattern is related to FVPs and WPW, which is suggestive of extensive cardiac involvement.

473 Chloroma: an unusual case with extensive cardiac involvement detected by echocardiography

Abstract Introduction Chloroma, also known as myeloid sarcoma, is a localized extramedullary tumour composed of malignant cells of the myeloid cell line, most frequently occurring in myelogenous leukemia. Heart involvement is exceptional, only about 20 cases have been reported in the literature. Case presentation A 38-year-old woman presenting with fatigue and pre-syncope was admitted to the hospital. The patient had a history of acute myeloid leukaemia diagnosed 2017, treated with chemotherapy and transplanted with allogenic bone-marrow the same year, remaining thereafter in clinical remission. Initial electrocardiogram showed sinus bradycardia and recurrent sinus arrests and therefore a pacemaker was implanted. An echocardiogram was performed which revealed multiple infiltrative masses with involvement of the superior vena cava extending to the right atrium, atrial septum, left atrium, mitral valve and aortic root. Magnetic resonance imaging was done confirming the echocardiographic results and showing even involvement of pulmonary veins, coronary arteries and myocardial infiltration. Chemoradiation was administered with initial response, however, disease progression led to the patients´death. Conclusion To our knowledge, this is the first case describing a chloroma with extensive involvement of cardiac walls, vessels and valves. This case also illustrates the value of echocardiography as a tool for early detection of cardiac masses. Abstract 473 Figure. Echo with contrast

Primary mediastinal large B-cell lymphoma with extensive cardiac involvement

Data regarding the optimal therapeutic approach of patients with primary mediastinal B-cell lymphoma and cardia c involvement are limited. Reports suggest that multi-agent systemic chemotherapy, along with radiation therapy, may be effective in the treatment of these patients.

Cardiac mucormycosis: a case report.

BackgroundMucormycosis is an invasive fungal infection (IFI) most commonly seen in immunocompromised patients. Diabetic ketoacidosis, haematopoietic transplantation, iron overload states, and deferoxamine therapy are considered to be some of the classical risk factors. While cutaneous and rhino-sinusoidal forms may be seen in immunocompetent (IC) individuals, cardiac and mediastinal involvement is rare. In this report, we describe a young patient without predisposing factors who presented as mediastinal mucormycosis with extensive cardiac involvement.Case summaryA 19-year-old male presented with complaints of dry cough and dyspnoea on exertion over the last 4 months. Echocardiography showed diffuse infiltration of both atria along with multiple pedunculated freely mobile masses. A computed tomography chest was done to further delineate the true extent of the disease and revealed diffuse infiltration of the mediastinum, bilateral atria and interatrial septum, pulmonary veins, and superior vena cava. A fine needle aspiration cytology from a mediastinal mass revealed broad aseptate fungal hyphae with right angled branching consistent with Mucor. Extensive evaluation could not find any predisposing factors. The patient was started on Amphotericin B and surgical debridement was contemplated. However, owing to the diffuse infiltration around the heart and mediastinal vasculature, debridement could not be performed and the patient eventually succumbed to the illness.DiscussionMediastinal mucormycosis though rare in IC patients, is a rapidly progressive condition with a high fatality. A high index of suspicion needs to be maintained in individuals presenting with infiltrative disorders of the mediastinum for early diagnosis and prompt treatment.

Arguable ICD placement in a sarcoidosis patient with extensive cardiac involvement.

Arguable ICD placement in a sarcoidosis patient with extensive cardiac involvement.

Disseminated Mucormycosis with Extensive Cardiac Involvement

Mucormycosis is an opportunistic fungal infection. Cardiac involvement is a rare, yet fatal, complication that can occur in disseminated disease. A strong index of suspicion is necessary for prompt treatment, especially in high-risk patients. We present a 62-year-old male patient with a history of diabetes and acute myeloid leukemia; he had pulmonary mucormycosis that was complicated by cardiac involvement as part of disseminated mucormycosis syndrome.

2 Massive Cardiac Metastases of an Untreated, Inflammatory Breast Cancer in a Young Patient: A Case Report of Autopsy Findings and Review of the Literature

Inflammatory breast carcinoma is a rare, aggressive form of breast cancer with a rapid onset and a poor prognosis. Extensive lymphovascular invasion characterizes this disease process. Cardiac involvement is rare and usually is clinically unknown until autopsy examination. A case report of a 47-year-old Hispanic woman with inflammatory breast carcinoma and widely metastatic disease, including extensive cardiac involvement is presented. A literature review of this disease and the mechanism of retrograde pulmonary/mediastinum lymphatic microembolism is included. A literature review on the benefits of better access to medical care for underserved populations is also discussed. At the time of autopsy, metastases involving the lungs, liver, and mediastinal lymph nodes, as well as pleural and pericardial effusions were observed grossly. Microscopic examination confirmed massive cardiac metastases, including involvement of the myocardium. Additionally, unexpected involvement of multiple other organs was identified, including dermal lymphatic permeation of abdominal skin. Inflammatory breast cancer is an aggressive, rapidly progressive, and often fatal disease. Cardiac metastases are rare with inflammatory breast carcinoma, and the mechanism of cardiac dysfunction requires further study. This case illustrates the known devastating nature of this disease. It also provides the opportunities to study the cardiac dysfunction associated with myocardial metastases, and the need for improved access to medical care in underserved populations for early detection and treatment of disease.

Antiproteinase 3 Positive Eosinophilic Granulomatosis with Polyangiitis Presenting with Heart Failure and Intraventricular Thrombosis

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis commonly with cardiac complications. We describe a case of anti-PR3 ANCA-positive EGPA complicated by congestive heart failure and intraventricular thrombosis. Interestingly, the thrombus was resolved rapidly with steroid and cyclophosphamide in the setting of interrupted anticoagulation. To the best of our knowledge, we report the first case of anti-PR3 positive EGPA with extensive cardiac involvement. Our patient had overlapping features with previously studied ANCA-positive and ANCA-negative EGPA cases. We also hypothesize that the thrombogenic potential of eosinophils may play a central role in thrombogenesis in EGPA and aggressive immunosuppressive therapy remains the cornerstone of treatment, and the addition of anticoagulation therapy in the setting of thrombus formation and also very high risk of bleeding needs to be considered cautiously.

Systemic sclerosis (scleroderma): An insight into a rare condition and cause of death

Systemic sclerosis is a debilitating and rare autoimmune disease with only approximately 200 cases in Singapore (from 2008-2012). Cardiovascular and pulmonary involvement remain the leading causes of mortality in these patients. We present a 46-year-old Chinese male who was found dead in his home. He had presented to the emergency department with generalised weakness, dysphagia and skin thickening prior to his demise, prompting a presumptive diagnosis of scleroderma. He also had anaemia and mild transaminitis. Significant autopsy findings included thickened skin and extensive adhesions in the pleural cavity. Histological sections showed extensive subendocardial fibrosis with vasculopathy affecting the intramural myocardial vessels as well as pulmonary arterial hypertension. Fibrosis involving the wall of the oesophagus and the dermis was also present. An interesting finding was that of extensive hyalinisation of the lymph nodes in the deceased. Our findings concur with those described previously in literature and the likely cause of mortality in our case was due to extensive cardiac and pulmonary involvement. Most of the mortalities occurring from this condition are not subjected to the coroner's jurisdiction. However, the rare case that presents at the autopsy suite does provide an educational insight to the pathology behind the condition.

Erdheim-Chester Disease Associated with Marginal Zone Lymphoma and Monoclonal Proteinemia

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis. We report a fatal case of ECD with extensive cardiac involvement associated with a marginal zone lymphoma and monoclonal proteinemia in a young man. This is the first reported association of ECD with a monoclonal gammopathy or a lymphoma.

Children and adolescents with fabry disease

Despite the observation that severe clinical signs and symptoms, with the exception of neuropathic pain and gastrointestinal symptoms, are rare in pediatric patients with Fabry disease, studies have shown extensive organ involvement in all pediatric patients. A recent study of renal biopsy findings in children and adolescents with Fabry disease (7 males, 2 females; age range, 7-18 years), all with normal estimated glomerular filtration rate (eGFR), found GL-3 accumulation in all patients and a broad spectrum of abnormalities, including glomerular, tubulointerstitial, and vascular changes, in many patients.? Another study in 20 children and adolescents (12 fe­ males, 8 males; age range, 6-16 years), without any overt cardiac signs or symptoms, found that all patients had a left ventricular mass indexed to height greater than the 75th percentile of healthy controls. 8 In addition, this study reported that heart rate variability in all male patients was significantly lowered (P < 0.05), suggesting a reduced parasympathetic stimulation of the heart. Results of these studies support the claim that pediatric pa­ tients with Fabry disease can have extensive renal and cardiac involvement, albeit subclinical, in addition to the overt neuropathic and gastrointestinal signs and symptoms. Enzyme replacement therapy (ERT) has been found to be well tolerated 9 ,!O and to reduce GL-3 accumulation in the dermal capillary endothelium 9 in pediatric patients with Fabry disease. However, the optimal age at which ERT should be initiated has not yet been determined. Research in adult patients with mild to moderate kidney disease found that ERT slowed the progression of the disease and was more effective in patients with less severe renal involvement, as determined by eGFR values.!! This finding supports the notion that initiation of ERT before substantial-and potentially irreversible---damage has occurred will provide greater clinical benefit. Extensive GL-3 accumulation may be present in pediatric patients with Fabry disease from an early age, result­ ing in demonstrable functional abnormalities in many patients; therefore, investigating whether initiating ERT during childhood (at least in male patients) might prevent disease progression appears justified. In addition, if ERT is started at an early stage of the disease, various dosage or dosing intervals may be efficacious. A random­ ized, multicenter, open-label study was recently initiated to evaluate the efficacy and tolerability of treating male pediatric Fabry disease patients without severe symptoms using a low-dose regimen of ERT (agalsidase beta 0.5 mg/kg every 2 weeks vs 1 mg/kg every 4 weeks).!2 This study was started in October 2008, and the goal is to include 45 patients. The study's estimated primary completion date is December 2014. In conclusion, Fabry disease can have serious clinical signs and symptoms during childhood which necessitate vigorous follow-up studies so that ERT can be initiated before irreversible damage has occurred. Studies on the efficacy of early intervention in children are greatly needed.

Arrhythmogenesis and diagnosis of cardiac sarcoidosis. An immunohistochemical study in a sudden cardiac death

We present an uncommon case of sudden cardiac death in a 34-year-old white woman. She was found lifeless at home by her parents. Three months before death she was recovered at the Emergency Room for chest pain, palpitation and loss of consciousness. Subsequent cardiological evaluation with ECG showed sinusal rhythm, QRS deviation to the left, QS aspect, asymmetric and rounded T waves and slight length of QT. During hospitalization she presented some episodes of supraventricular paroxysmal tachycardia and non-sustained ventricular tachycardia. No echocardiography alterations were found. An anti-arrhythmic treatment was prescribed. Autopsy revealed some fibrotic scarring in the myocardium of left ventricle. The histological examination of the heart revealed diffuse and extensive fibrosis with non-caseating sarcoid granulomas. The lungs, kidneys and lymph node also showed the same non-caseating granulomas. The diagnosis of sarcoidosis with massive and extensive cardiac involvement was established as cause of death.

Cardiac Metastasis of a Malignant Fibrous Histiocytoma Occupying the Right Ventricle and Infiltrating the Myocardium

A 86-year-old woman presented with a cardiac tumor occupying the whole cavity of the right ventricle and causing right ventricular outflow obstruction. A percutaneous ultrasound-guided biopsy was performed and histologic examination revealed a metastasis of a malignant fibrous histiocytoma. Because of the extensive cardiac involvement and multiple pulmonary metastases, effective surgical therapy was not possible and the patient died soon after diagnosis.

Cardiac Tumor as an Initial Manifestation of Acquired Immunodeficiency Syndrome

A cardiac tumor was the first manifestation of acquired immunodeficiency syndrome (AIDS) in a female patient in a state of severe immunodeficiency caused by human immunodeficiency virus (HIV) infection. The extensive cardiac and extracardiac involvement shown by various imaging modalities, including echocardiography and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), suggested that she was in the critical stage of non-Hodgkin's lymphoma (NHL). AIDS was treated by highly active-antiretroviral therapy and the NHL was treated by a combination of rituximab-cyclophosphamide-vincristine-doxorubicine-predonisolone. After 6 cycles of chemotherapy, she was in complete remission. Her cardiac tumor dramatically reduced in size and FDG-PET showed no positive uptake on whole body imaging. Generally, an AIDS-related cardiac tumor tends to be diagnosed at the late stage of the disease because of its nonspecific clinical findings, resulting in an extremely poor prognosis. In the present case, the cardiac tumor was detected by echocardiography and treated with appropriate chemotherapy. Early diagnosis and prompt treatment may improve a patient's prognosis.

Complex congenital cardiac disease in a patient with partial trisomy for the long arms of chromosomes 11 and 22

Abnormalities of chromosomes 11 and 22 are associated with congenital cardiac disease and/or various syndromes. We present a patient with partial trisomy for the long arms of chromosomes 11 and 22, the result of a maternal balanced reciprocal translocation between these two chromosomes. Our patient was dysmorphic and had coarctation of the aorta, an atrioventricular septal defect with common atrioventricular junction and exclusively atrial shunting, patency of the arterial duct, supracardiac totally anomalous pulmonary venous connection, a single kidney, and tracheobronchomalacia. This patient is unusual in having extensive left-sided cardiac involvement, a feature not usually found in this condition.

Large Aneurysms of the Ascending Aorta and Major Coronary Arteries in a Patient With Hereditary Hemorrhagic Telangiectasia

We describe a 50-year-old man with a history of hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease) who presented with chest pain, atrial fibrillation, and congestive heart failure. Echocardiography revealed a large ascending aortic aneurysm accompanied by severe aortic regurgitation and giant coronary artery aneurysms involving the right, left main, left anterior descending, and circumflex coronary arteries. Coronary angiography clearly defined multiple aneurysms involving the aorta and coronary arteries. The patient underwent complex and successful surgical repair of the aneurysms. To our knowledge, this is the first reported case of extensive cardiac involvement in a patient with this uncommon genetic disorder.

Cardiac metastases

The authors found metastases to the heart in 10.7% of 1029 autopsy cases in which a malignant neoplasm was diagnosed. The lung was the commonest primary site (36.4%) and adenocarcinoma was the most frequent cell type (36.4%) of neoplasms metastatic to heart. Nonepithelial tumors accounted for 22.7% of cardiac metastases. Epicardium was involved in 75.5% of metastatic lesions and a pericardial effusion was present with 33.7% of epicardial metastases. Although hemorrhagic effusions occurred in only 12 cases with metastases to heart, these represented 76.4% of all such effusions. Lymphomas associated with the acquired immune deficiency syndrome showed the most extensive cardiac involvement. Primary sites and cell types of cardiac metastases have evolved over time and have been modified by chemotherapy, increased survival of cancer patients, increasing incidence of lung carcinoma, and recently by the acquired immune deficiency syndrome epidemic.

Amyloid in the aged heart: frequency and clinical significance.

Cardiac amyloid accumulation is a common autopsy finding in elderly persons, the frequency increasing with each advancing age decade. In most cases the deposits are microscopic, confined to the atrial subendocardium, and of dubious significance. In a few cases, however, there is much more extensive cardiac involvement, with infiltration of the ventricular musculature and intracardiac conduction system. In the authors' recent autopsy study of 100 patients over 60 years of age, 10 had diffuse cardiac amyloidosis with biventricular involvement. Microscopically, the amyloid deposits often resembled foci of interstitial fibrosis. Significant cardiac enlargement (weight greater than 380 gm) was present in only 2 of these patients, and in only one of them were the clinical signs and symptoms clearly attributable attributable to the amyloid infiltration. It was difficult to assess the possible contribution of ventricular amyloid to congestive failure since most of the patients also had coronary arteriosclerosis. In the aged, clinically significant cardiac amyloidosis associated with cardiac enlargement appears to be part of a disease spectrum more commonly characterized by focal, clinically insignificant cardiac amyloid deposits. Yet several features suggest that senile cardiac amyloidosis may differ from the clinically significant cardiac amyloidosis occassionally seen in younger patients.