Cardiac Angiosarcoma. A Review

Based on a case of a patient with angiosarcoma (AS) of the right atrium with superior vena cava syndrome associated with urticaria and polyarthralgias, who died soon after surgery, the authors present a brief review of the subject of cardiac AS, an extremely rare pathology, usually diagnosed late due to its non-specific symptomatology. Several topics are discussed, including mechanisms of clinical manifestations caused by blood flow obstruction and valve dysfunction, local invasion with arrhythmias and pericardial effusion, embolic phenomena and constitutional symptoms. Imaging and histopathologic methods of diagnosis are considered, as well as references to cytogenetic analysis. Surgery is the first treatment choice, but heart AS are frequently not completely resectable and concomitant metastases at the time of surgery are common, both usually leading to a dismal prognosis. Chemotherapy, radiotherapy and even heart transplantation do not substantially improve the survival of these patients. Urticaria is not generally assumed by most authors to be associated with malignancy, but there are rare reports of its association with some malignant tumors.

The Proarrhythmic Effect of Cardiac Resynchronization Therapy: an Issue that Should Be Borne in Mind

The demonstrated benefits of cardiac resynchronization therapy (CRT) in reducing mortality and hospitalizations for heart failure, improving NYHA functional class and inducing reverse remodeling have led to its increasing use in clinical practice. However, its potential contribution to complex ventricular arrhythmias is controversial.We present the case of a female patient with valvular heart failure and severe systolic dysfunction, in NYHA class III and under optimal medical therapy, without previous documented ventricular arrhythmias. After implantation of a CRT defibrillator, she suffered an arrhythmic storm with multiple episodes of monomorphic ventricular tachycardia (VT), requiring 12 shocks. Subsequently, a pattern of ventricular bigeminy was observed, as well as reproducible VT runs induced by biventricular pacing. Since no other vein of the coronary sinus system was accessible, it was decided to implant an epicardial lead to stimulate the left ventricle, positioned in the left ventricular mid-lateral wall. No arrhythmias were detected in the following six months. This case highlights the possible proarrhythmic effect of biventricular pacing with a left ventricular lead positioned in the coronary sinus venous system.

Insights into the clinical and functional significance of cardiac autonomic dysfunction in Chagas disease

INTRODUCTION: Exclusive or associated lesions in various structures of the autonomic nervous system occur in the chronic forms of Chagas disease. In the indeterminate form, the lesions are absent or mild, whereas in the exclusive or combined heart and digestive disease forms, they are often more pronounced. Depending on their severity these lesions can result mainly in cardiac parasympathetic dysfunction but also in sympathetic dysfunction of variable degrees. Despite the key autonomic effect on cardiovascular functioning, the pathophysiological and clinical significance of the cardiac autonomic dysfunction in Chagas disease remains unknown. METHODS: Review of data on the cardiac autonomic dysfunction in Chagas disease and their potential consequences, and considerations supporting the possible relationship between this disturbance and general or cardiovascular clinical and functional adverse outcomes. RESULTS: We hypothesise that possible consequences that cardiac dysautonomia might variably occasion or predispose in Chagas disease include: transient or sustained arrhythmias, sudden cardiac death, adverse overall and cardiovascular prognosis with enhanced morbidity and mortality, an inability of the cardiovascular system to adjust to functional demands and/or respond to internal or external stimuli by adjusting heart rate and other hemodynamic variables, and immunomodulatory and cognitive disturbances. CONCLUSIONS: Impaired cardiac autonomic modulation in Chagas disease might not be a mere epiphenomenon without significance. Indirect evidences point for a likely important role of this alteration as a primary predisposing or triggering cause or mediator favouring the development of subtle or evident secondary cardiovascular functional disturbances and clinical consequences, and influencing adverse outcomes.

Ventricular arrhythmias in Chagas disease

Sudden death is one of the most characteristic phenomena of Chagas disease, and approximately one-third of infected patients develop life-threatening heart disease, including malignant ventricular arrhythmias. Fibrotic lesions secondary to chronic cardiomyopathy produce arrhythmogenic substrates that lead to the appearance and maintenance of ventricular arrhythmias. The objective of this study is to discuss the main clinical and epidemiological aspects of ventricular arrhythmias in Chagas disease, the specific workups and treatments for these abnormalities, and the breakthroughs needed to determine a more effective approach to these arrhythmias. A literature review was performed via a search of the PubMed database from 1965 to May 31, 2014 for studies of patients with Chagas disease. Clinical management of patients with chronic Chagas disease begins with proper clinical stratification and the identification of individuals at a higher risk of sudden cardiac death. Once a patient develops malignant ventricular arrhythmia, the therapeutic approach aims to prevent the recurrence of arrhythmias and sudden cardiac death by the use of implantable cardioverter defibrillators, antiarrhythmic drugs, or both. In select cases, invasive ablation of the reentrant circuit causing tachycardia may be useful. Ventricular arrhythmias are important manifestations of Chagas cardiomyopathy. This review highlights the absence of high-quality evidence regarding the treatment of ventricular arrhythmias in Chagas disease. Recognizing high-risk patients who require specific therapies, especially invasive procedures such as the implantation of cardioverter defibrillators and ablative approaches, is a major challenge in clinical practice.

Study of the cardiac alterations in HIV-infected children consequent to the antiretroviral therapy: prospective study of 47 cases

OBJECTIVE: Detect of cardiac alterations in children with AIDS and compare their evolution with the administration of only one anti-retroviral and the recent cases who received drugs in combination. METHODS: We prospectively studied 47 children in 3 groups: group 1, 20 cases treated only with zidovudine; group 2, 10 patients treated initially with zidovudine and later with a combination of drugs and in group 3, 17 patients, who receiced two or three since the beginning. In all patients it was done chest X-ray, EKG and echocardiography every 6 months and after death complete pathological study. RESULTS: Among the 45 patients cases 26 (57%) were index cases. Malnutrition, diarrhea tachycardia, signs of congestive heart failure, pericardial effusion, abnormal ventricular repolarization and arrhythmias were more frequent in group 1. Echocardiographic abnormalities were present in 10 (50%) children of group 1. They were less frequent in the others two groups. In regard to the outcome in group 1, two patients had worsening of sings of cardiomyopaty and 4 died. Cardiac dysfunction in all cases of group 2 and 3 improved with the medication. CONCLUSION:- The children who received combination and their cardiac alterations had more favorable outcome than those who received only one drug.

Characterization of the in vivo cardiac electrophysiologic effects of high-dose cocaine in closed-chest, anesthetized dogs with normal hearts

OBJECTIVE: To characterize the cardiac electrophysiologic effects of cocaine. METHODS: In 8 dogs (9-13 kg), electrophysiologic parameters and programmed stimulation were undertaken using transvenous catheters at baseline, and after cocaine intravenous infusion (12 mg/kg bolus followed by 0.22 mg/kg/min for 25 minutes). RESULTS: Cocaine plasma levels (n=5) rose to 6.73± 0.56 mg/mL. Cocaine did not affect sinus cycle length and arterial pressure. Cocaine prolonged P wave duration (54±6 vs 73±4 ms, P<0.001), PR interval (115±17 vs 164±15 ms, P<0.001), QRS duration (62±10 vs 88±14 ms, P<0.001), and QTc interval (344±28 vs 403±62 ms, P=0.03) but not JT interval (193±35 vs 226±53 ms, NS). Cocaine prolonged PA (9±6 vs 23±8 ms, P<0.001), AH (73±16 vs 92±15 ms; P=0.03), and HV (35±5 vs 45±3ms; P<0.001) intervals and Wenckebach point (247±26 vs 280±28 ms, P=0.04). An increase occurred in atrial (138±8 vs 184± 20 ms; P<0.001) and ventricular (160±15 vs 187±25 ms; P=0.03) refractoriness at a cycle length of 300 ms. Atrial arrhythmias were not induced in any dog. Ventricular fibrillation (VF) was induced in 2/8 dogs at baseline and 4/8 dogs after cocaine. CONCLUSION: High doses of cocaine exert significant class I effects and seem to enhance inducibility of VF but not of atrial arrhythmias.

Prevention of Pazopanib-Induced Prolonged Cardiac Repolarization and Proarrhythmic Effects

Background: Pazopanib (PZP) may induce prolonged cardiac repolarization and proarrhythmic effects, similarly to other tyrosine kinase inhibitors. Objectives: To demonstrate PZP-induced prolonged cardiac repolarization and proarrhythmic electrophysiological effects and to investigate possible preventive effects of metoprolol and diltiazem on ECG changes (prolonged QT) in an experimental rat model. Methods: Twenty-four Sprague-Dawley adult male rats were randomly assigned to 4 groups (n = 6). The first group (normal group) received 4 mL of tap water and the other groups received 100 mg/kg of PZP (Votrient® tablet) perorally, via orogastric tubes. After 3 hours, the following solutions were intraperitoneally administered to the animals: physiological saline solution (SP), to the normal group and to the second group (control-PZP+SP group); 1 mg/kg metoprolol (Beloc, Ampule, AstraZeneca), to the third group (PZP+metoprolol group); and 1mg/kg diltiazem (Diltiazem, Mustafa Nevzat), to the fourth group (PZP+diltiazem group). One hour after, and under anesthesia, QTc was calculated by recording ECG on lead I. Results: The mean QTc interval values were as follows: normal group, 99.93 ± 3.62 ms; control-PZP+SP group, 131.23 ± 12.21 ms; PZP+metoprolol group, 89.36 ± 3.61 ms; and PZP+diltiazem group, 88.86 ± 4.04 ms. Both PZP+metoprolol and PZP+diltiazem groups had significantly shorter QTc intervals compared to the control-PZP+SP group (p < 0.001). Conclusion: Both metoprolol and diltiazem prevented PZP-induced QT interval prolongation. These drugs may provide a promising prophylactic strategy for the prolonged QTc interval associated with tyrosine kinase inhibitor use.

Cardiac Remodeling: Concepts, Clinical Impact, Pathophysiological Mechanisms and Pharmacologic Treatment

Abstract Cardiac remodeling is defined as a group of molecular, cellular and interstitial changes that manifest clinically as changes in size, mass, geometry and function of the heart after injury. The process results in poor prognosis because of its association with ventricular dysfunction and malignant arrhythmias. Here, we discuss the concepts and clinical implications of cardiac remodeling, and the pathophysiological role of different factors, including cell death, energy metabolism, oxidative stress, inflammation, collagen, contractile proteins, calcium transport, geometry and neurohormonal activation. Finally, the article describes the pharmacological treatment of cardiac remodeling, which can be divided into three different stages of strategies: consolidated, promising and potential strategies.

Clinical review: practical recommendations on the management of perioperative heart failure in cardiac surgery.

Acute cardiovascular dysfunction occurs perioperatively in more than 20% of cardiosurgical patients, yet current acute heart failure (HF) classification is not applicable to this period. Indicators of major perioperative risk include unstable coronary syndromes, decompensated HF, significant arrhythmias and valvular disease. Clinical risk factors include history of heart disease, compensated HF, cerebrovascular disease, presence of diabetes mellitus, renal insufficiency and high-risk surgery. EuroSCORE reliably predicts perioperative cardiovascular alteration in patients aged less than 80 years. Preoperative B-type natriuretic peptide level is an additional risk stratification factor. Aggressively preserving heart function during cardiosurgery is a major goal. Volatile anaesthetics and levosimendan seem to be promising cardioprotective agents, but large trials are still needed to assess the best cardioprotective agent(s) and optimal protocol(s). The aim of monitoring is early detection and assessment of mechanisms of perioperative cardiovascular dysfunction. Ideally, volume status should be assessed by 'dynamic' measurement of haemodynamic parameters. Assess heart function first by echocardiography, then using a pulmonary artery catheter (especially in right heart dysfunction). If volaemia and heart function are in the normal range, cardiovascular dysfunction is very likely related to vascular dysfunction. In treating myocardial dysfunction, consider the following options, either alone or in combination: low-to-moderate doses of dobutamine and epinephrine, milrinone or levosimendan. In vasoplegia-induced hypotension, use norepinephrine to maintain adequate perfusion pressure. Exclude hypovolaemia in patients under vasopressors, through repeated volume assessments. Optimal perioperative use of inotropes/vasopressors in cardiosurgery remains controversial, and further large multinational studies are needed. Cardiosurgical perioperative classification of cardiac impairment should be based on time of occurrence (precardiotomy, failure to wean, postcardiotomy) and haemodynamic severity of the patient's condition (crash and burn, deteriorating fast, stable but inotrope dependent). In heart dysfunction with suspected coronary hypoperfusion, an intra-aortic balloon pump is highly recommended. A ventricular assist device should be considered before end organ dysfunction becomes evident. Extra-corporeal membrane oxygenation is an elegant solution as a bridge to recovery and/or decision making. This paper offers practical recommendations for management of perioperative HF in cardiosurgery based on European experts' opinion. It also emphasizes the need for large surveys and studies to assess the optimal way to manage perioperative HF in cardiac surgery.

Effects of flecainide on exercise-induced ventricular arrhythmias and recurrences in genotype-negative patients with catecholaminergic polymorphic ventricular tachycardia.

BACKGROUND: Conventional therapy with beta-blockers is incompletely effective in preventing arrhythmic events in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT). We have previously discovered that flecainide in addition to conventional drug therapy prevents ventricular arrhythmias in patients with genotype-positive CPVT. OBJECTIVE: To study the efficacy of flecainide in patients with genotype-negative CPVT. METHODS: We studied the efficacy of flecainide for reducing ventricular arrhythmias during exercise testing and preventing arrhythmia events during long-term follow-up. RESULTS: Twelve patients with genotype-negative CPVT were treated with flecainide. Conventional therapy failed to control ventricular arrhythmias in all patients. Flecainide was initiated because of significant ventricular arrhythmias (n = 8), syncope (n = 3), or cardiac arrest (n = 1). At the baseline exercise test before flecainide, 6 patients had ventricular tachycardia and 5 patients had bigeminal or frequent ventricular premature beats. Flecainide reduced ventricular arrhythmias at the exercise test in 8 patients compared to conventional therapy, similar to that in patients with genotype-positive CPVT in our previous report. Notably, flecainide completely prevented ventricular arrhythmias in 7 patients. Flecainide was continued in all patients except for one who had ventricular tachycardia at the exercise test on flecainide. During a follow-up of 48±94 months, arrhythmia events (sudden cardiac death and aborted cardiac arrest) associated with noncompliance occurred in 2 patients. Flecainide was not discontinued owing to side effects in any of the patients. CONCLUSIONS: Flecainide was effective in patients with genotype-negative CPVT, suggesting that spontaneous Ca(2+) release from ryanodine channels plays a role in arrhythmia susceptibility, similar to that in patients with genotype-positive CPVT.

Atrial arrhythmias in adults with congenital heart disease.

BACKGROUND: Atrial arrhythmias increase disease burden in the general adult population. Adults with congenital heart lesions constitute a rapidly growing group of patients with cardiovascular disease. We hypothesized that atrial arrhythmias increase with age and impair health outcomes in this population. METHODS AND RESULTS: We conducted a population-based analysis of prevalence, lifetime risk, mortality, and morbidity associated with atrial arrhythmias in adults with congenital heart disease from l983 to 2005. In 38 428 adults with congenital heart disease in 2005, 5812 had atrial arrhythmias. Overall, the 20-year risk of developing atrial arrhythmia was 7% in a 20-year-old subject and 38% in a 50-year-old subject. More than 50% of patients with severe congenital heart disease reaching age 18 years developed atrial arrhythmias by age 65 years. In patients with congenital heart disease, the hazard ratio of any adverse event in those with atrial arrhythmias compared with those without was 2.50 (95% confidence interval, 2.38 to 2.62; P<0.0001), with a near 50% increase in mortality (hazard ratio, 1.47; 95% confidence interval, 1.37 to 1.58; P<0.001), more than double the risk of morbidity (stroke or heart failure) (hazard ratio, 2.21; 95% confidence interval, 2.07 to 2.36; P<0.001), and 3 times the risk of cardiac interventions (hazard ratio, 3.00; 95% confidence interval, 2.81 to 3.20; P<0.001). CONCLUSIONS: Atrial arrhythmias occurred in 15% of adults with congenital heart disease. The lifetime incidence increased steadily with age and was associated with a doubling of the risk of adverse events. An increase in resource allocation should be anticipated to deal with this increasing burden.

Postpacing abnormal repolarization in catecholaminergic polymorphic ventricular tachycardia associated with a mutation in the cardiac ryanodine receptor gene.

BACKGROUND Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an arrhythmogenic disease for which electrophysiological studies (EPS) have shown to be of limited value.OBJECTIVE This study presents a CPVT family in which marked postpacing repolarization abnormalities during EPS were the only consistent phenotypic manifestation of ryanodine receptor (RyR2) mutation carriers.METHODS The study was prompted by the observation of transient marked QT prolongation preceding initiation of ventricular fibrillation during atrial fibrillation in a boy with a family history of sudden cardiac death (SCD). Family members underwent exercise and pharmacologic electrocardiographic testing with epinephrine, adenosine, and flecainide. Noninvasive clinical test results were normal in 10 patients evaluated, except for both epinephrine- and exercise-induced ventricular arrhythmias in 1. EPS included bursts of ventricular pacing and programmed ventricular extrastimulation reproducing short-long sequences. Genetic screening involved direct sequencing of genes involved in long QT syndrome as well as RyR2.RESULTS Six patients demonstrated a marked increase in QT interval only in the first beat after cessation of ventricular pacing and/or extrastimulation. All 6 patients were found to have a heterozygous missense mutation (M4109R) in RyR2. Two of them, presenting with aborted SCD, also had a second missense mutation (I406T- RyR2). Four family members without RyR2 mutations did not display prominent postpacing QT changes.CONCLUSION M4109R- RyR2 is associated with a high incidence of SCD. The contribution of I406T to the clinical phenotype is unclear. In contrast to exercise testing, marked postpacing repolarization changes in a single beat accurately predicted carriers of M4109R- RyR2 in this family.

Cardiac and neurologic outcome of cardiac rhabdomyoma considerations for prenatal counseling

Abstract : Cardíac rhabdomyomas are benign cardiac tumors with few cardiac complications but with a known association to tuberous sclerosis that affects the neurologic outcome of the patients. Thís study analyses the long-term cardiac and neurological outcome of patients with cardiac rhabdomyomas in order to allow comprehensive prenatal counseling. qll prenatal and postnatal cases with echocardiographic diagnosis of cardiac rhabdomyomas encountered from August 1982 -September 2007 have been recorded. Independent factors, such às the number and the location of the tumors, have been analyzed for association with a diagnosis of tuberous sclerosis, in order to predict the cardiac and neurologic outcome of the patients. Cardiac complications include arrhythmias, outflow tract obstruction, secondary cardiogenic shock. Arrhythmias are the most often encountered problems during the neonatal period. Supraventricular tachycardia is the commonest rhythm disturbance identified. However, no specific dimension or location of the cardiac rhabdomyomas may predict the rhythm disturbances. The importance of the diagnosis of tuberous sclerosis in patients presenting with cardiac rhabdomyomas is exemplified by the neurodevelopmental complications showing 80% of cases with epilepsy and 63% of cases with a delayed development. The presence of multiple cardiac tumors in patients suggests a higher risk to be affected by tuberous sclerosis, compared to patients with a single tumor. Cardiac rhabdomyomas generally regress aftér birth and after the perinatal period cardiac-related problems are rare, but tuberous sclerosis and the associated neurodevelopmental complications dominate the clinical picture and should form an important aspect of the prenatal counseling of parents. Résumé : Les rhabdomyomes cardiaques sont des tumeurs cardiaques bénignes avec toutefois des complications. cardiaques possibles et surtout avec une association pour la sclérose tubéreuse de Bourneville qui détermine le pronostic neurologique. Cette étude présente une analyse du suivi cardiologique. et neurologique à long terme d'enfants avec un diagnostic de rhabdomyomes cardiaques dans le but de mieux informer les parents lors de la consultation anténatale. L'ensemble des cas de rhabdomyomes cardiaques diagnostiqués au moyen de l'échocardiographie pendant la période anténatale ainsi que postnatale a été répertorié d'août 1982 à septembre 2007. Des facteurs indépendants, tels que le nombre et la localisation des tumeurs, ont été analysés pour leur association avec le diagnostic de la sclérose tubéreuse de Bourneville, afin de prédire le pronostic cardiaque et neurologique de ces patients. Les complications cardiaques retrouvées sont les arythmies, les obstructions des voies d'éjection ventriculaire et le choc cardiogène secondaire. Les arythmies sont les problèmes les plus fréquemment rencontrés pendant la période néonatale.. La tachycardie supraventriculaire est le trouble de rythme le plus souvent identifié. Néanmoins, il n'y a pas de dimension ou de localisation.- spécifique d'un rhabdomyome cardiaque qui pourrait prédire ces troubles du rythme. L'importance de l'association au diagnostic de la sclérose tubéreuse de Bourneville chez les patients atteints de rhabdomyomes est démontrée à travers les complications du développement neurologique avec une attéinte épileptique dans 80% des cas ainsi qu'un retard de développement dans 63% des cas. La présence de multiples tumeurs cardiaques chez un patient suggère un risque accru d'être atteint de la sclérose tubéreuse de Bourneville comparé à un patient atteint d'une tumeur unique. Les rhabdomyomes cardiaques régressent après la naissance et après la période périnatale les complications cardiaques deviennent rares. Toutefois, l'association à la sclérose tubéreuse de Bourneville domine le tableau clinique avec des complications au niveau du développement neurologique et formé donc un aspect important lors de la consultation anténatale.