Sawsan Awad

Pediatric cardiac interventions.

The field of pediatric cardiac interventions has witnessed a dramatic increase in the number and type of procedures performed. We review the most common procedures performed in the catheter laboratory. Lesions are divided according to their physiological characteristics into left-to-right shunting lesions (atrial septal defect, patent ductus arteriosus, ventricular septal defect), right-to-left shunting lesions (pulmonary stenosis, pulmonary atresia/intact ventricular septum), right heart obstructive lesions (peripheral arterial pulmonic stenosis, right ventricular outflow tract obstruction), and left heart obstructive lesions (aortic valve stenosis, coarctation of the aorta). In addition, a miscellaneous group of lesions is discussed.

Inositol‐1,4,5‐trisphosphate induced Ca2+ release and excitation–contraction coupling in atrial myocytes from normal and failing hearts

Impaired calcium (Ca2+) signalling is the main contributor to depressed ventricular contractile function and occurrence of arrhythmia in heart failure (HF). Here we report that in atrial cells of a rabbit HF model, Ca2+ signalling is enhanced and we identified the underlying cellular mechanisms. Enhanced Ca2+ transients (CaTs) are due to upregulation of inositol‐1,4,5‐trisphosphate receptor induced Ca2+ release (IICR) and decreased mitochondrial Ca2+ sequestration. Enhanced IICR, however, together with an increased activity of the sodium–calcium exchange mechanism, also facilitates spontaneous Ca2+ release in form of arrhythmogenic Ca2+ waves and spontaneous action potentials, thus enhancing the arrhythmogenic potential of atrial cells. Our data show that enhanced Ca2+ signalling in HF provides atrial cells with a mechanism to improve ventricular filling and to maintain cardiac output, but also increases the susceptibility to develop atrial arrhythmias facilitated by spontaneous Ca2+ release.

NFAT transcription factor regulation by urocortin II in cardiac myocytes and heart failure

Urocortin II (UcnII), a cardioactive peptide with beneficial effects in normal and failing hearts, is also arrhythmogenic and prohypertrophic. We demonstrated that cardiac effects are mediated by a phosphatidylinositol-3 kinase (PI3K)/Akt kinase (Akt)/endothelial nitric oxide synthase (eNOS)/nitric oxide (NO) signaling pathways. Nuclear factor of activated T-cells (NFAT) transcription factors play a key role in the regulation of gene expression in cardiac development, maintenance of an adult differentiated cardiac phenotype, and remodeling processes in cardiac hypertrophy and heart failure (HF). We tested the hypothesis that UcnII differentially regulates NFAT activity in cardiac myocytes from both normal and failing hearts through the PI3K/Akt/eNOS/NO pathway. Isoforms NFATc1 and NFATc3 revealed different basal subcellular distribution in normal and HF rabbit ventricular myocytes with a nuclear NFATc1 and a cytosolic localization of NFATc3. However, in HF, the nuclear localization of NFATc1 was less pronounced, whereas the nuclear occupancy of NFATc3 was increased. In normal myocytes, UcnII induced nuclear export of NFATc1 and attenuated NFAT-dependent transcriptional activity but did not affect the distribution of NFATc3. In HF UcnII facilitated nuclear export of both isoforms and reduced transcriptional activity. NFAT regulation was mediated by a PI3K/Akt/eNOS/NO signaling cascade that converged on the activation of several kinases, including glycogen synthase kinase-3β (GSK3β), c-Jun NH2-terminal kinase (JNK), p38 mitogen-activated kinase (p38), and PKG, resulting in phosphorylation, deactivation, and nuclear export of NFAT. In conclusion, while NFATc1 and NFATc3 reveal distinct subcellular distribution patterns, both are regulated by the UcnII-PI3K/Akt/eNOS/NO pathway that converges on the activation of NFAT kinases and NFAT inactivation. The data reconcile cardioprotective and prohypertrophic UcnII effects mediated by different NFAT isoforms.

Prenatal Detection of Congenital Heart Disease: Time for a Breakthrough

To borrow Churchill’s 1939 description of Russia, fetal wellbeing ever since man’s creation was a ‘‘riddle, wrapped in a mystery, inside an enigma’’ till the advent of medical ultrasonography. We are now able to identify with increasing accuracy the intricacies of cardiac pathology; however, the rates of prenatal detection of congenital heart disease (CHD), the most common type of birth defects in humans, continue to be suboptimal at best. The reported rates have been quite disappointing, ranging between 15 and 48 % with most being reported to be less than 30 % [4, 6, 9]. Even more recently, two published retrospective studies in high-risk populations at four major United States tertiary care centers, which take into account the use of more advanced technology and equipment, reported rates of detection of 24–36 % [5, 8]. This obviously continues to emphasize the poor prenatal detection rate and to stress the need for further improvement in this area. This year, the American Institute of Ultrasound in Medicine (AIUM), in conjunction with the American College of Radiology (ACR), the American College of Obstetricians and Gynecologists (ACOG) and the Society of Radiologists in Ultrasound (SRU), published the revised practice guidelines for the performance of Obstetric Ultrasound Examinations [1]. These guidelines, like those previously published, include essential minimal or mandatory elements as part of the standard ultrasound examination of fetal anatomy during the secondand thirdtrimester scan. Unlike the previous guidelines, however, this year’s publication includes a major change in screening the fetal heart in low risk pregnancies. The previous guidelines state that a basic cardiac examination should include a 4-chamber view of the fetal heart and, only when ‘‘technically feasible’’, views of the outflow tracts. The current guidelines, finally, clearly emphasize the inclusion of both the right and left outflow tracts view in addition to the 4-chamber view as an integral part of the minimal elements of the ultrasonographic assessment of the fetal heart. This significant change comes after various studies demonstrated the importance of adding the outflow tracts view to the routine prenatal screening ultrasound in addition to the four-chamber view. This has been shown to result in significant improvement in the detection rate of CHD of up to 70 %, as has been shown by Carvalho et al. [3] in a high-risk population and 74 % as recently shown by a study by Levy et al. [7] in a large low-risk population. The outflow tracts view has been shown to be more sensitive than the four-chamber view in detecting CHD in general as well as in detecting ductal-dependent forms of CHD [8]. This leaves no doubt that, in order to achieve a better prenatal detection rate of CHD in the general population, the addition of the outflow views to the routine fetal screening examination has to become mandatory. Given the importance of prenatal and early detection of congenital heart disease on postnatal outcome [2], these published practice guidelines will undoubtedly have a significant impact on the practice of fetal medicine. These guidelines represent an important effort to raise the bar and improve the rate of prenatal detection of CHD and as such advance the field of fetal cardiology. The inclusion of the assessment of both the 4-chamber and outflow tracts views in the screening process in large low-risk pregnancies, however, undoubtedly places a significant burden on practicing obstetricians and obstetric sonographers, many of whom were not trained to obtain K. A. Diab (&) S. Awad Pediatric Cardiology, Rush University Medical Center, 1653 W Congress Parkway, Chicago, IL 606012, USA e-mail: karim_diab@rush.edu

Routine Cardiac Catheterization Prior to Fontan Operation: Is It a Necessity?

Prior to the Fontan procedure, patients with single ventricle physiology with Glenn shunt are typically referred for cardiac catheterization to assess hemodynamics and potentially provide interventional measures. Currently, echocardiography provides detailed information which together with other non-invasive imaging such as CT scan and MRI may obviate the need for routine cardiac catheterization prior to the Fontan procedure. In this study, we examine the findings in cardiac catheterization in this population to determine: (a) the accuracy of echocardiography in providing adequate information prior to the Fontan procedure, particularly in identifying those in need of per-catheter intervention, and (b) the percentage of patients requiring interventional procedures during cardiac catheterization. We performed a retrospective chart review of echocardiographic and cardiac catheterization data for patients who underwent pre-Fontan cardiac catheterization at our center in the period from 02/01/2008 to 02/28/2017. We aimed to re-examine the necessity of routine cardiac catheterization in all single ventricle patients. This was performed through examining pre-catheterization echocardiography reports and comparing them to findings of the subsequent cardiac catheterization reports. Echocardiography reports were evaluated for accuracy in identifying significant anatomical or hemodynamic findings, which may impact success of Fontan procedure as well as the ability of echocardiography to predict findings important to know prior to the Fontan procedure. In this cohort of 40 children, 3 patients were found to have significant hemodynamic findings through cardiac catheterization which were not previously known by echocardiography. In addition, 28 out of 40 patients (70%) required interventional procedures to address significant abnormalities (systemic to pulmonary arterial collaterals, pulmonary artery stenosis, aortic arch stenosis, etc.). All cases of aortic arch stenosis were detected by echocardiography, however, all patients who required systemic to pulmonary arterial or left SVC embolization were not detected by echocardiography. Furthermore, echocardiography did not detect the need for branch pulmonary artery stenosis in 50% of cases. Cardiac catheterization appears to be an essential part of patient assessment prior to Fontan completion in patients with single ventricle physiology. This current practice may change in the future if a non-invasive screening tool is found to have high positive and negative predictive values in identifying the subset of patients who require potential intervention in pre-Fontan cardiac catheterization.

Reversible cardiomyopathy in an adolescent with idiopathic aortic cusp ventricular tachycardia.

This report describes the case of an asymptomatic patient with a ventricular tachycardia-induced cardiomyopathy that resolved completely after successful radiofrequency ablation. This type of presentation and outcome has not been reported in the pediatric literature.

Coronary Artery Bypass Grafting in Single-Ventricle Patients Palliated with Fontan Procedure: Future Consideration

‘‘A new surgical procedure has been used which transmits the whole vena caval blood to the lungs, while only oxygenated blood returns to the left heart. The right atrium is, in this way, ‘ventriclized’, to direct the inferior vena caval blood to the left lung, the right pulmonary artery receiving the superior vena caval blood through a cava-pulmonary anastomosis’’. By this statement, Fontan and Baudet started their article detailing the first Fontan procedure in 1971 [6]. Since 1971, the Fontan procedure has been applied for palliation of single-ventricle physiology patients. Multiple modifications of the original procedure were applied to improve morbidities and mortalities. Numerous investigators studied the shortand long-term outcomes of the procedure [5, 7]. The 32nd Bethesda conference in 2001 discussed the issue of caring of these patients going into adolescent and adulthood [1]. It is around the same time when The British Cardiac Society released its report detailing plans for care of the grown-up with congenital heart disease [12]. The rise of the new adult congenital heart disease specialty was dictated by the need for appropriate care given to the growing number of patients that currently exceeded the number of children with congenital heart disease, thanks to advances in medicine and surgery. One of the risk factors of failing Fontan, also a result of Fontan, is the presence of aorto-pulmonary collateral arteries (APCs). APCs are present in up to 80 % of singleventricle patients undergoing pre-Fontan catheterization. Pre-Fontan coil occlusion of these vessels decreases singleventricle volume load and improves outcome after Fontan procedure [8, 9, 14, 16]. These collateral vessels are usually branches of the right and left subclavian arteries including the left internal mammary artery (LIMA) and the right internal mammary artery (RIMA). Branches of subclavian arteries and intercostal arteries normally have extensive anastomotic connections with LIMA and RIMA. Successful occlusion of the APCs requires obliteration of the whole length of the vessel to prevent revascularization by distal feeder tributaries. In adults with coronary artery disease not amenable to percutaneous stenting, coronary artery bypass grafting (CABG) is the standard of care. LIMA is used in almost every patient and is the cardiac surgeon’s blood vessel of choice for CABG due to its superior long-term patency compared to other vessels [2, 10]. RIMA is used in less number of CABG cases due to the lack of anatomical proximity to the target coronary vessels. It is usually used in grafting the right coronary artery when feasible with patency equivalent to LIMA. Other arterial and venous grafts options are less frequently used with variable patency. The internal mammary arteries are strikingly resistant to the development of atherosclerosis secondary, at least in part, to its superior endothelial function with fewer fenestrations, lower intercellular junction permeability, greater anti-thrombotic molecules such as heparin sulfate and tissue plasminogen activator, higher endothelial nitric oxide (NO) production and its impermeability to the transfer of atherosclerosis producing lipoproteins [17]. Early cases of single-ventricle physiology palliated with Fontan procedure are in their 30 and 40s. This group of patients is approaching the common age of coronary artery S. Awad (&) Rush Center for Congenital Heart Disease, Rush University Medical Center, 1653 Congress PKWY, Jones 773, Chicago, IL 60612, USA e-mail: Sawsan_m_awad@rush.edu

Prenatal Diagnosis of Isolated Levocardia and a Structurally Normal Heart: Two Case Reports and a Review of the Literature

Isolated levocardia (ILC) is a developmental abnormality involving an abnormal abdominal situs with a normal cardiac situs. This abnormality is especially rare when it is associated with a normal cardiac anatomy. The prenatal diagnoses of seven cases were reported in the English literature. This report presents two cases referred to the authors’ echocardiography laboratory for maternal diabetes mellitus in case 1 and suspected dextrocardia in case 2. In both cases, ILC with a structurally normal heart was diagnosed prenatally. The child in the first case was found to have a normal inferior vena cava (IVC) prenatally. Postnatally, he was found to have intestinal malrotation with duodenal obstruction and multiple splenules. Interruption of the IVC was shown by abdominal ultrasound. The child in the second case was found to have an interrupted IVC with azygos continuation prenatally. Postnatally, intestinal malrotation with no evidence of intestinal obstruction or asplenia was detected. Neither of the cases had reported cardiac arrhythmias. Early diagnosis is crucial in these cases due to the high incidence of associated anomalies and potential life-threatening conditions. Management of patients with ILC is dictated by the associated anomalies. Long-term follow-up assessment is recommended for these patients to monitor the development of rhythm abnormalities.

Current and future therapy for pulmonary hypertension in patients with right and left heart failure

Pulmonary hypertension (PH) is a devastating condition that without proper management can deteriorate progressively. Elevated pulmonary artery pressure without an identifiable etiology is called IPAH. PH resulting from a specific disease is referred to as secondary PH; left-sided cardiac disease can lead to an increase in pulmonary artery pressure resulting in increased vascular resistance and subsequent structural remodeling. If left-sided failure progresses to right-sided failure with high pulmonary artery pressure, the outcome is ominous. It has been clearly proven that early diagnosis and effective medical therapy can markedly decrease morbidity and mortality. In this review, we discuss the current treatment modalities and their limitations for PH secondary to heart failure. Conventional therapy in patients with pulmonary arterial hypertension as well as recent advances in the medical management of PH in general, are also described. Last, the surgical management of these patients and other promising interventional modalities are reviewed.

Coronary Sinus Defect Following Transcatheter Closure of ASD Using Amplatzer Septal Occluder: Potential Erosion by the Device

We present a case of small coronary sinus defect detected after transcatheter device closure of a large secundum atrial septal defect. Although device erosion of the dilated coronary sinus is suspected, the defect in the coronary sinus may have been present prior to ASD device closure. Dilated coronary sinus may be a risk factor when closing a secundum ASD with a device. To the best of our knowledge, coronary sinus erosion by an ASD device has not yet been reported in the medical literature.