Gentian Lluri

Coronary Arterial Development: A Review of Normal and Congenitally Anomalous Patterns

Coronary artery development is a delicate, complex, and finely tuned process that includes multiple interactions among many pathways, especially in the pericardium and the developing myocardium. There still exists some controversy on the exact origin of certain cellular components. Nevertheless, an understanding of this extremely important developmental process is paramount in identifying some of the causes of anomalous coronary development. There are different patterns of anomalous coronary arteries, with variable risk of myocardial ischemia, malignant arrhythmias, and sudden cardiac death. These anomalies can be broadly categorized into 2 basic anatomic subsets: those with origin of the anomalous coronary artery from the opposite aortic sinus, and those with origin of the anomalous coronary artery from the pulmonary artery. Diagnosis and management of such patterns continues to be challenging. A good knowledge of the normal and abnormal coronary artery development could potentially help us explore new avenues in the treatment of ischemic heart disease as well as anomalous coronary arteries.

WNT Signaling in Cardiac and Vascular Disease

WNT signaling is an elaborate and complex collection of signal transduction pathways mediated by multiple signaling molecules. WNT signaling is critically important for developmental processes, including cell proliferation, differentiation and tissue patterning. Little WNT signaling activity is present in the cardiovascular system of healthy adults, but reactivation of the pathway is observed in many pathologies of heart and blood vessels. The high prevalence of these pathologies and their significant contribution to human disease burden has raised interest in WNT signaling as a potential target for therapeutic intervention. In this review, we first will focus on the constituents of the pathway and their regulation and the different signaling routes. Subsequently, the role of WNT signaling in cardiovascular development is addressed, followed by a detailed discussion of its involvement in vascular and cardiac disease. After highlighting the crosstalk between WNT, transforming growth factor-β and angiotensin II signaling, and the emerging role of WNT signaling in the regulation of stem cells, we provide an overview of drugs targeting the pathway at different levels. From the combined studies we conclude that, despite the sometimes conflicting experimental data, a general picture is emerging that excessive stimulation of WNT signaling adversely affects cardiovascular pathology. The rapidly increasing collection of drugs interfering at different levels of WNT signaling will allow the evaluation of therapeutic interventions in the pathway in relevant animal models of cardiovascular diseases and eventually in patients in the near future, translating the outcomes of the many preclinical studies into a clinically relevant context.

Fibromuscular dysplasia of the left anterior descending coronary artery.

A 40-year-old man with no known past medical history was admitted for severe depression. A 12-lead electrocardiogram was obtained before electroconvulsive therapy, which revealed ST-segment elevations in V2 to V3. The patient denied any symptoms. Physical examination was unremarkable. Cardiac

Incidence and outcome of infective endocarditis following percutaneous versus surgical pulmonary valve replacement

To provide a comparison of the outcome of infective endocarditis (IE) in patients undergoing transcatheter pulmonary valve replacement (TPVR) versus surgical pulmonary valve replacement (SPVR).

Radiation coronary arteritis refractory to surgical and percutaneous revascularization culminating in orthotopic heart transplantation.

BACKGROUND Hodgkins lymphoma (HL) comprises of 4% of malignancies diagnosed in children from birth to 14 years of age. While overall survival rates have increased, HL survivors can be at risk of late cardiovascular complications from radiotherapy. HL survivors with a history of mediastinal RT have been found to have an increased incidence of myocardial infarction, angina, congestive heart failure, and valvular disorders compared to the general population. METHODS A 33 year old female with a history of HL status post chemotherapy and mediastinal radiation 11 years ago became symptomatic with multivessel coronary artery disease with aggressive progression of her disease despite coronary bypass graft surgery, patch angioplasty of the left main coronary artery (LMCA) with an extracellular bioscaffold, and repeated percutaneous coronary intervention of the LMCA. She eventually underwent orthotopic heart transplant and did well postoperatively. RESULTS Histopathological analysis of the explanted heart revealed a variety of sequelae of radiation arteritis, including thrombosis of both native vessels and arterial grafts, intimal hyperplasia and involvement of the bioscaffold in the left main coronary vasculature. The bioscaffold did not contribute significantly to the stenosis within the LMCA. CONCLUSION Our case demonstrates an unusual indication for OHT due to severe refractory radiation induced CAD, as well the wide spectrum of the histopathologic manifestations of radiation induced arteritis.

Prognostic Significance of Left Ventricular Fibrosis in Patients With Congenital Bicuspid Aortic Valve

This study sought to evaluate the prognostic value of left ventricular (LV) fibrosis assessed by late gadolinium enhancement (LGE) of the myocardium during cardiac magnetic resonance (CMR) imaging in patients with bicuspid aortic valve (BAV), which is associated with early aortic valve fibrosis and calcification. To what degree the LV myocardial wall is affected by fibrosis and its prognostic value is currently unknown. This is a retrospective, single-center study evaluating all adult patients with BAV who had CMR and followed from March 2002 to March 2016. CMR and transthoracic echocardiogram images were reviewed. Clinical data were abstracted from the electronic medical record. A total of 29 patients were included in the study, of which 11 (38%) had CMR studies that demonstrated the presence of LGE. Patients with LGE had significantly higher aortic valve mean gradients by echocardiography when compared with LGE-negative patients (30.3 ± 7.2 mm Hg vs 14.7 ± 3.6 mm Hg, p = 0.049). They were also more likely to have LV hypertrophy. Patients with LGE were 10 times more likely to need aortic valve replacement within 1 year of the CMR study than did patients without LGE (55% vs 5.5%, p = 0.0028). In conclusion, evaluation of LGE by CMR as a marker of LV myocardial fibrosis can have additional prognostic value when evaluating patients with aortic stenosis secondary to BAV.

Hematopoietic progenitors are required for proper development of coronary vasculature

RATIONALE During embryogenesis, hematopoietic cells appear in the myocardium prior to the initiation of coronary formation. However, their role is unknown. OBJECTIVE Here we investigate whether pre-existing hematopoietic cells are required for the formation of coronary vasculature. METHODS AND RESULTS As a model of for hematopoietic cell deficient animals, we used Runx1 knockout embryos and Vav1-cre; R26-DTA embryos, latter of which genetically ablates 2/3 of CD45(+) hematopoietic cells. Both Runx1 knockout embryos and Vav1-cre; R26-DTA embryos revealed disorganized, hypoplastic microvasculature of coronary vessels on section and whole-mount stainings. Furthermore, coronary explant experiments showed that the mouse heart explants from Runx1 and Vav1-cre; R26-DTA embryos exhibited impaired coronary formation ex vivo. Interestingly, in both models it appears that epicardial to mesenchymal transition is adversely affected in the absence of hematopoietic progenitors. CONCLUSION Hematopoietic cells are not merely passively transported via coronary vessel, but substantially involved in the induction of the coronary growth. Our findings suggest a novel mechanism of coronary growth.

Systemic to pulmonary venous collaterals in adults with single ventricle physiology after cavopulmonary palliation

OBJECTIVES To assess the frequency, anatomic characteristics, and associations of systemic to pulmonary venous collaterals in adult patients undergoing cardiac catheterization after a Fontan operation. Additionally, the embryologic basis for the presence of venous collaterals is reviewed. METHODS Cardiac catheterization data was reviewed for 66 adults with single ventricle physiology and a Fontan palliation. RESULTS There were a total of 66 patients that underwent catheterization between 2004 and 2014 at the Ahmanson/UCLA Adult Congenital Heart Disease Center. There were 24 males and 42 females. Systemic venous to pulmonary venous collaterals were present in 38 patients (58%), most commonly originating from the right brachiocephalic vein (35%), azygous vein (20%) and superior vena cava (13%). Trans-catheter interventional closure was performed in 27/38 (71%) of patients with venous collaterals. At baseline these patients had lower oxygen saturation when compared to those not requiring intervention, 85.6% ± 6.1% vs 89.9% ± 5.4%, p < 0.05. At 6 months, the ambulatory systemic saturation improved from 85.6% ± 6.1% to 91.8% ± 6.4%, p < 0.05. At two years follow-up, the ambulatory systemic saturation had decreased to 90.5% ± 4.1% (p < 0.05). CONCLUSION In adults with single ventricle physiology and prior Fontan surgery, systemic venous collaterals are common and can be percutaneously occluded at minimal risk with resultant improvement in systemic oxygen saturation on long term follow up. When evaluated from a developmental standpoint, 85% of collaterals are above the diaphragm and could be secondary to recanalization of the collateral veins, an embryological connection between systemic and pulmonary veins.

Applications of Cardiac CT in the Tetralogy of Fallot Patient

In various subsets of tetralogy of Fallot (TOF) patients, the anatomic heterogeneity, myriad of potential surgical palliations, and the potentially associated intracardiac and extracardiac anomalies encountered must be taken into consideration when imaging a patient with TOF. Multidetector cardiac

Thromboprophylaxis in Adults With Atrio-Pulmonary Fontan

Background: Although aspirin has been compared to warfarin for thromboembolic prophylaxis in the general Fontan population, little is known about the optimal preventative strategy for the atriopulmonary right atrium–pulmonary artery [RA-PA]) Fontan particularly. Methods: A retrospective cohort study was performed including adult patients identified in the Ahmanson/UCLA Adult Congenital Heart Disease Center database with a history of RA-PA Fontan and use of either aspirin or warfarin as most recent primary prophylaxis against thromboembolism. Primary outcome was incident thromboembolism, defined as space-occupying lesion on imaging consistent with thrombus within the Fontan or pulmonary arterial circuit. Secondary outcomes were death, transplantation, Fontan conversion, and bleeding requiring either transfusion or invasive intervention. Follow-up was terminated upon achievement of a primary outcome or achievement of a secondary outcome other than bleeding. Kaplan-Meier analysis of freedom from thrombosis was performed. Results: Twenty-six patients met inclusion criteria. Thirteen (50%) received aspirin as most recent primary prophylaxis and 13 (50%) received warfarin. Tricuspid atresia was the most common underlying diagnosis (42%), followed by double-inlet left ventricle (38%). Median age at Fontan operation was 8.2 years; median age at prophylaxis initiation was 25.9 years. After six years, the aspirin group had 50% ± 35% freedom from thrombosis and the warfarin group 92% ± 8% (P = .15). Incidences of secondary outcomes were not significantly different between the groups. Conclusion: In this cohort of long-term Fontan survivors with RA-PA Fontan, the risk of thromboembolic complications is high, especially in those taking aspirin rather than warfarin. Larger studies are needed to confirm these findings.