Elisabetta Mariucci

Management of Pulmonary Arterial Hypertension Associated with Congenital Systemic-to-Pulmonary Shunts and Eisenmenger’s Syndrome

A large proportion of patients with congenital heart disease (CHD), in particular those with relevant systemic-to-pulmonary shunts, will develop pulmonary arterial hypertension (PAH) if left untreated. Persistent exposure of the pulmonary vasculature to increased blood flow, as well as increased pressure, may result in pulmonary obstructive arteriopathy, which leads to increased pulmonary vascular resistance that, if it approaches or exceeds systemic resistance, will result in shunt reversal. Eisenmenger’s syndrome, the most advanced form of PAH associated with CHD, is defined as CHD with an initial large systemic-to-pulmonary shunt that induces severe pulmonary vascular disease and PAH, with resultant reversal of the shunt and central cyanosis.The histopathological and pathobiological changes seen in patients with PAH associated with congenital systemic-to-pulmonary shunts, such as endothelial dysfunction of the pulmonary vasculature, are considered similar to those observed in idiopathic or other associated forms of PAH. A pathological and pathophysiological classification of CHD with systemic-to-pulmonary shunt leading to PAH has been developed that includes specific characteristics, such as the type, dimensions and direction of the shunt, extracardiac abnormalities and repair status. A clinically oriented classification has also been proposed.The prevalence of PAH associated with congenital systemic-to-pulmonary shunts in Western countries has been estimated to range between 1.6 and 12.5 cases per million adults, with 25–50% of this population affected by Eisenmenger’s syndrome.Clinically, Eisenmenger’s syndrome presents with multiple organ involvement, with progressive deterioration of function over time. The signs and symptoms of Eisenmenger’s syndrome in the advanced stages include central cyanosis, dyspnoea, fatigue, haemoptysis, syncope and right-sided heart failure. Survival of patients with Eisenmenger’s syndrome is clearly less than that of the general population, but appears to be better than that of patients with idiopathic PAH in a comparable functional class.The treatment strategy for patients with PAH associated with congenital systemic-to-pulmonary shunts and, in particular, those with Eisenmenger’s syndrome is based mainly on clinical experience rather than being evidence based. General measures include recommendations for physical activity, pregnancy, infections, air travel, exposure to high altitudes and elective surgery, and that psychological assistance be provided as necessary. Phlebotomies are required only when hyperviscosity of the blood is evident, usually when the haematocrit is >65%. The use of supplemental oxygen therapy is controversial and it should be used only in patients in whom it produces a consistent increase in arterial oxygen saturation. Oral anticoagulant treatment with warfarin can be initiated in patients with pulmonary artery thrombosis and absent, or only mild, haemoptysis.The following three classes of drugs targeting the correction of abnormalities in endothelial dysfunction have been approved recently for the treatment of PAH: (i) prostanoids; (ii) endothelin receptor antagonists; and (iii) phosphodiesterase-5 inhibitors. The efficacy and safety of these compounds have been confirmed in uncontrolled studies in patients with PAH associated with corrected and uncorrected congenital systemic-to-pulmonary shunts, as well as in patients with Eisenmenger’s syndrome. One randomized controlled trial reported favourable short- and long-term outcomes of treatment with the orally active dual endothelin receptor antagonist bosentan in patients with Eisenmenger’s syndrome. Lung transplantation with repair of the cardiac defect or combined heart-lung transplantation are options for Eisenmenger’s syndrome patients with a poor prognosis. A treatment algorithm based on the one used in the treatment of PAH patients is proposed for patients with PAH associated with corrected and uncorrected congenital systemic-to-pulmonary shunts and Eisenmenger’s syndrome.

Long-term incidence of atrial fibrillation and flutter after transcatheter atrial septal defect closure in adults

BACKGROUND The long-term risk of atrial fibrillation and flutter (AFF) after trascatheter atrial septal defects (ASD) closure in adults is unknown. METHODS We studied 134 patients who have undergone transcatheter ASD closure at our institution at an age of > 18 years (mean age 39 +/- 16 years); Patients were followed-up for 4.8 +/- 2.7 years (range 0.8-9.6 years). We assessed the presence of AFF both before and after ASD closure using standard 12 lead ECGs or 24h ambulatory Holter monitors. RESULTS 13 patients (10%) had documented AFF before the procedure (paroxysmal in 6, permanent in 7). Patients with AFF before the procedure were older (p < 0.0001), and had worse clinical condition (p = 0.0008). Patients without a history of AFF before the procedure and those who experienced paroxysmal AFF before the procedure had a very low annual risk (0%) of subsequent permanent AFF at long-term follow-up. Four patients with permanent AFF before the procedure (onset of < 12months) underwent electrical cardioversion immediately before ASD closure. Two of them (50%) are in sinus rhythm after 4.1 and 7.0 years, respectively. CONCLUSIONS Transcatheter ASD closure performed in adults with no history of AFF or with a history of paroxysmal AFF before closure seems to protect from development of AFF in the long-term. In selected patients with permanent AFF at closure, device ASD closure together with arrhythmia cardioversion might be able to restore and maintain sinus rhythm in the long-term.

Spontaneous coronary artery dissection in a young woman with Loeys–Dietz syndrome

Spontaneous Coronary Artery Dissection in a Young Woman With Loeys–Dietz Syndrome Rossella Fattori,* Pietro Sangiorgio, Elisabetta Mariucci, Marco Ritelli, Anita Wischmeijer, Cristiano Greco, and Marina Colombi Marfan Center, Cardiothoracovascular Department, University Hospital S.Orsola, Bologna, Italy Invasive Cardiology Laboratory, Department of Cardiology, Maggiore Hospital, Bologna, Italy Division of Biology and Genetics, Department of Biomedical Sciences and Biotechnology, University of Brescia, Brescia; Italy Department of Medical Genetics, University Hospital S. Orsola, Bologna, Italy Clinical Genetics Unit, Arcispedale S. Maria Nuova, Reggio Emilia, Italy

Dilation of peripheral vessels in Marfan syndrome: importance of thoracoabdominal MR angiography.

OBJECTIVES Aim of this study was to assess vascular morphology and dimension of the entire aorta and branch vessels in MFS using thoracoabdominal MR angiography (MRA). BACKGROUND Evaluation of vascular involvement in Marfan Syndrome (MFS) is focused to the ascending aorta, which has the major risk of dissection/rupture. METHODS From March 2006 to January 2011, 64 patients (35 ± 13 years old) with MFS underwent echocardiography and MRA of thoracic and abdominal aorta. Measurements of ascending aorta, aortic arch, descending thoracic and abdominal aorta, and aortic branch vessels were assessed. In patients with aortic dissection only non dissected vessels were considered for measurements. RESULTS 64 Marfan patients were divided into 2 groups: patients in natural history (group A, 55%) and patients previously submitted to aortic root and/or ascending aorta replacement because of severe aortic dilation or dissection (group B, 45%). Dilation of the descending aorta, mostly of the aortic isthmus, occurred in 18/53 patients (8/35 group A, 10/18 group B). Abdominal aorta resulted in the normal range in group A and in 16/18 patients of group B, while iliac vessels were dilated in 7/35 patients of group A and in 10/23 patients of group B. Four patients of group B presented isolated dilation of subclavian, celiac, mesenteric, or renal arteries. CONCLUSIONS Vascular dilation beyond the aortic root is not uncommon in MFS. The systematic use of MRA provides a comprehensive evaluation of the entire arterial system.

Incompatibility between intravenous amiodarone and heparin in an infant

Amiodarone is an effective antiarrhythmic agent and represents the drug of choice in the treatment of severe arrhythmias, especially in the setting of ventricular dysfunction. Amiodarone has the potential for interaction with many cardiac and non-cardiac drugs. Nonetheless few incompatibilities have been reported. We report the incompatibility between amiodarone and heparin administrated in the same vein in a case of a one month old baby with atrial flutter. This topic needs more attention, due to the frequent co-administration of these two drugs in tachyarrhythmias with high thromboembolic risk.

Sex differences in congenital heart defects and genetically induced arrhythmias.

Sex medicine can be applied to define the effect of male or female sex-associated differences on the prevalence of congenital heart defects (CHDs), on clinical manifestation of the latter, on means of dealing with the defects and facing consequent surgical treatment, as well as on the success of surgery. The widespread use of modern databases has undoubtedly enhanced the possibility of these observations compared to the past, when findings were limited to case series from single cardiology or paediatric heart surgery units. The aim of the present review is to assess all publications present in the literature on sex differences and CHD, placing particular emphasis on both contradictory aspects and less acknowledged issues. Furthermore, a section of the review is devoted to the effect of sex differences on cardiac arrhythmias, particularly the largely genetically predetermined electrophysiological differences observed between men and women.

Results and complications of permanent pacing in pediatric patients with congenital or acquired atrioventricular block

BACKGROUND Currently there is no evidence to prefer an endocardial or epicardial approach for pacing in pediatric patients. This analysis was aimed at defining the complications of pacemaker implantation in a pediatric population with atrioventricular block according to a strategy of choosing an epicardial system for patients <10 kg and an endocardial system for patients >10 kg. METHODS This is a retrospective study performed on 27 patients, with and without congenital heart disease, implanted with a permanent pacemaker because of idiopathic or acquired atrioventricular block at our Pediatric Cardiology and Cardiac Surgery Unit of S. Orsola-Malpighi Hospital in Bologna (Italy) between 1981 and 2010. Patients were divided into two groups: 70% of the population (group A) was implanted with an epicardial system, 30% (group B) with an endocardial system. RESULTS After a mean follow-up of 14 years (17 ± 8 years for group A, 7 ± 5 years for group B), the most frequent complications were lead failure (44%) and infection (18%). Both were more common in the epicardial system group: lead failure rate 53% in group A vs 25% in group B (p=0.0001); infection rate 26% in group A vs 0% in group B (p=0.0001); rate of system revision or implantation of a new electrode 42% in group A vs 12% in group B (p=0.0001). CONCLUSIONS The present study demonstrates a high complication rate in patients undergoing an epicardial pacing system implantation. However, in patients <10 kg the epicardial system allows subclavian venous access protection for endocardial system implantation after somatic growth, avoiding high-risk procedures of system revision or lead extraction and subclavian vein occlusion in the long term.

Diagnostic Accuracy of Aortic Root Cross-sectional Area/Height Ratio in Children and Young Adults with Marfan and Loeys-Dietz Syndrome

BACKGROUND Accurate quantification of aortic dilatation is critical in children with syndromes associated with thoracic aortic aneurysm, yet classification of normality is difficult. Current methods of normalization use body surface area to account for growth, despite a nonlinear relationship of body surface area to aortic root dimensions. In contrast, height has a linear relationship with aortic root dimensions in normal children, is simple to measure and requires no secondary calculation. We evaluated the diagnostic accuracy of an height-based aortic root-indexing method, aortic root cross-sectional area/height ratio (AHr), in children with Marfan and Loeys-Dietz syndromes. METHODS A cohort of 54 children with Marfan or Loeys-Dietz syndromes, aged 3 months to 17 years, were evaluated with a transthoracic echocardiogram. AHr was measured in diastole at sinuses of Valsalva (SoV) and proximal ascending aorta (pAA) in a group of normal subjects matched for age and body surface area and normal values were provided. AHr values were recorded for patients and compared with z-scores results obtained with Gautiers and Campenss nomograms. RESULTS AHr values in the group of normal subjects were 2.6 ± 0.6 at SoV and 2 ± 0.5 at pAA. Categorization of z-scores and AHr showed good correspondence between AHr and Gautiers method (P = .341 at SoV and .185 at pAA) and AHr and Campens method (P =.465 at SoV and 0.110 at pAA). CONCLUSIONS There was a good correspondence of AHr results with two different z-scores. AHr is a simple to use and valid option to quantify aortic root dilatation in pediatric patients.

Sinus node dysfunction after partial anomalous pulmonary venous connection repair

OBJECTIVE Repair of partial anomalous pulmonary venous connection to superior vena cava using an internal patch has been described as a potential cause of obstruction at the systemic or pulmonary vein level and of sinus node dysfunction. Our experience with this operation was reviewed. METHODS From 1991 to 2011, 59 patients with a diagnosis of partial anomalous pulmonary venous connection to superior vena cava underwent surgical repair with intracardiac patch rerouting alone (45 patients) or with associated superior vena cava patch enlargement (14 patients). Follow-up evaluation was performed, including electrocardiogram, echocardiogram, electrocardiogram Holter monitor recording, and exercise stress test. RESULTS There were no early or late deaths and no reoperations at a mean follow-up of 46 ± 45 months. All patients were asymptomatic in New York Heart Association class I. Echocardiographic evaluation excluded any obstruction at the pulmonary or systemic vein level. At follow-up, 55 patients (93%) presented sinus rhythm and were free from antiarrhythmic medications, 2 patients (3%) presented atrial fibrillation, 1 patient (2%) presented atrial fibrillation and asymptomatic sinus node dysfunction, and 1 patient (2%) presented ectopic atrial rhythm. Electrocardiogram Holter recording demonstrated sinus node dysfunction in 6 of 34 patients (18%). Exercise stress test showed chronotropic incompetence in 8 of 27 patients (30%): All except 1 patient presented sinus rhythm at basal electrocardiogram, and only 4 patients had some evidence of sinus node dysfunction on electrocardiogram Holter recording. CONCLUSIONS Intracardiac repair of partial anomalous pulmonary venous connection can be performed with good results at medium-term follow-up. The rate of sinus node dysfunction or other arrhythmias and obstruction at pulmonary or systemic vein level is comparable to other techniques. Exercise stress test evaluation is the best way to detect asymptomatic sinus node dysfunction.

Le tachicardie sopraventricolari in età pediatrica

Supraventricular tachycardias in children still remain a challenge not only for the pediatrician, but also for the adult cardiologist who is facing an infant in an emergency situation. This review examines the unique aspects of pediatric arrhythmias, with particular emphasis on acute treatment and pharmacological prophylaxis. All current treatment options are focused, from the “old drugs” to the “novel ablative techniques”: the first are often able to defer the second to a more suitable age, with fewer adverse effects and higher success rates. A brief account on Wolff-Parkinson-White issues concludes the review.