Using Machine Learning to Elucidate the Spatial and Genetic Complexity of the Ascending Aorta

Background The left ventricular outflow tract (LVOT) and ascending aorta are spatially complex, with distinct pathologies and embryologic origins. Prior work examined genetics of thoracic aortic diameter in a single plane. We sought to elucidate the genetic basis for the diameter of the LVOT, the aortic root, and the ascending aorta. Methods We used deep learning to analyze 2.3 million cardiac magnetic resonance images from 43,317 UK Biobank participants. We computed the diameters of the LVOT, the aortic root, and at six locations in the ascending aorta. For each diameter, we conducted a genome-wide association study and generated a polygenic score. Finally, we investigated associations between these polygenic scores and disease incidence. Results 79 loci were significantly associated with at least one diameter. Of these, 35 were novel, and a majority were associated with one or two diameters. A polygenic score of aortic diameter approximately 13mm from the sinotubular junction most strongly predicted thoracic aortic aneurysm in UK Biobank participants (n=427,016; HR=1.42 per standard deviation; CI=1.34-1.50, P=6.67x10-21). A polygenic score predicting a smaller aortic root was predictive of aortic stenosis (n=426,502; HR=1.08 per standard deviation; CI=1.03-1.12, P=5x10-6). Conclusions We detected distinct common genetic loci underpinning the diameters of the LVOT, the aortic root, and at several segments in the ascending aorta. We spatially defined a region of aorta whose genetics may be most relevant to predicting thoracic aortic aneurysm. We further described a genetic signature that may predispose to aortic stenosis. Understanding the genetic contributions to the diameter of the proximal aorta may enable identification of individuals at risk for life-threatening aortic disease and facilitate prioritization of therapeutic targets.

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M26 How Does the Histology of the Aortic Root and Ascending Aorta Affect Aortic Aneurysm Progression and Surgical Repair?

Heart Lung and Circulation ◽

10.1016/j.hlc.2021.03.035 ◽

2021 ◽

Vol 30 ◽

pp. S11

Author(s):

T. Surman ◽

D. O'Rourke ◽

J. Finnie ◽

K. Reynolds ◽

J. Edwards ◽

...

Keyword(s):

Aortic Aneurysm ◽

Aortic Root ◽

Surgical Repair ◽

Ascending Aorta

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Evaluation of left ventricular function utilizing transesophageal echocardiography during and after thoracic aortic aneurysm repair

European Journal of Cardio-Thoracic Surgery ◽

10.1016/1010-7940(93)90069-n ◽

1993 ◽

Vol 7 (7) ◽

pp. 371-375 ◽

Cited By ~ 1

Author(s):

H IMAGAWA ◽

H TAKANO ◽

M KATO ◽

Y YOSHIOKA ◽

K OHNISHI

Keyword(s):

Aortic Aneurysm ◽

Left Ventricular Function ◽

Transesophageal Echocardiography ◽

Ventricular Function ◽

Thoracic Aortic Aneurysm ◽

Left Ventricular ◽

Aneurysm Repair ◽

Aortic Aneurysm Repair

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Abstract 5769: Correlation of Bicuspid Valve Morphology and Pattern of Aortic Root Dilatation: A Substudy of the Aortic Stenosis Progression Observation Measuring Effects of Rosuvastatin (ASTRONOMER) Study

Circulation ◽

10.1161/circ.118.suppl_18.s_998-b ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Kapil M Bhagirath ◽

Davinder S Jassal ◽

James W Tam ◽

Randy A Sochowski ◽

Jean G Dumesnil ◽

...

Keyword(s):

Aortic Stenosis ◽

Aortic Root ◽

Type A ◽

Left Ventricular ◽

Doppler Imaging ◽

Type B ◽

Root Parameters ◽

Standardized Protocol ◽

Aortic Root Dilatation ◽

Annular Calcification

Bicuspid aortic valve is the leading cause of aortic stenosis in patients younger than the age of 50. A classification scheme of bicuspid aortic valves (BAV) was recently proposed based upon leaflet orientation: Type A (fusion of right and left coronary cusps) and Type B (fusion of right and non-coronary cusps). The correlation between BAV leaflet orientation and aortic root pathology however remains ill defined. To describe a potential relationship between BAV leaflet morphology and aortic root measurements in the ASTRONOMER study, a multicentre study to assess the effect of Rosuvastatin on the progression of AS. Transthoracic echocardiography was performed with 2D and Doppler imaging following a standardized protocol. BAV morphology was classified as Type A or Type B orientation following review of the parasternal short-axis view. Echo measurements including left ventricular and aortic root dimensions were obtained according to the ASE recommendations. We identified 89 patients (56±11 years; 44 males). There were 63 patients with Type A and 26 with Type B BAV. Baseline demographic, hemodynamics, aortic root and left heart dimensions are listed in Table 1 . Patients with Type A BAV had larger aortic and ascending root dimensions than those patients with Type B BAV (p<0.05). Aortic valvular calcification and mitral annular calcification were similar between the two groups. All values are expressed as mean±SD. In patients with mild to moderate asymptomatic BAV, the presence of Type A valve orientation was associated with significantly greater aortic root parameters compared to Type B valve orientation. Whether the morphology of BAV may predict a subset of patients who will respond to statin therapy in preventing the progression of AS remains to be determined upon completion of the ASTRONOMER trial.

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Vascular Disease

Mayo Clinic Internal Medicine Board Review ◽

10.1093/med/9780190464868.003.0011 ◽

2016 ◽

pp. 129-142

Author(s):

Robert D. McBane

Keyword(s):

Risk Factors ◽

Aortic Aneurysm ◽

Vascular Disease ◽

Thoracic Aorta ◽

Thoracic Aortic Aneurysm ◽

Ascending Aorta ◽

Tobacco Exposure ◽

Degree Relative ◽

Men And Women ◽

Medial Degeneration

Aneurysms of the ascending aorta are typically due to medial degeneration, whereas aneurysms of the descending thoracic aorta are primarily due to atherosclerosis. Men and women are equally affected, and the prevalence of thoracic aortic aneurysm (TAA) increases with advancing age. Overall, the incidence is approximately 1 per 10,000 individuals, and 20% of patients with TAA have at least 1 affected first-degree relative. Typical risk factors include tobacco exposure, hypertension, infection, and trauma.

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P190 Chest pain and syncope in Turner"s syndrome: going beyond the obvious to not miss the critical diagnosis. Role of multimodality imaging approach

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jez319.060 ◽

2020 ◽

Vol 21 (Supplement_1) ◽

Author(s):

A Ruocco ◽

M Previtero ◽

N Bettella ◽

D Muraru ◽

S Iliceto ◽

...

Keyword(s):

Chest Pain ◽

Pericardial Effusion ◽

Aortic Valve ◽

Aortic Stenosis ◽

Aortic Dissection ◽

Severe Aortic Stenosis ◽

Left Ventricular ◽

Ascending Aorta ◽

Rule Out ◽

Typical Chest Pain

Abstract Clinical Presentation: a 18-year-old woman with Turner’s syndrome (TS), with history of hypothyroidism treated with L-thyroxin, asymptomatic moderately stenotic bicuspid aortic valve (AV) and without any known cardiovascular risk factor, was admitted to our emergency department (ED) because of syncope and typical chest pain after dinner associated with dyspnea. Chest pain lasted for an hour with spontaneous regression. In the ED the patient (pt) was normotensive. An ECG showed sinus rhythm (88 bpm), nonspecific repolarization anomalies (T wave inversion) in the inferior and anterior leads. Myocardial necrosis biomarkers were negative. A 3D transthoracic echocardiography showed normal biventricular systolic function with left ventricular hypertrophy, dilatation of the ascending aorta, unicuspid AV with severe aortic stenosis (peak/mean gradient 110/61 mmHg, aortic valve area 0,88 cm2-0,62 cm2/m2), mild pericardial effusion (Figure Panel A, B, C). Five days after, the pt had a new episode of typical chest pain without ECG changes. A computerized tomography (CT) was performed to rule out the hypothesis of aortic dissection and showed a dilation of the ascending aorta and pericardial effusion localized in the diaphragmatic wall, no signs of dissection or aortic hematoma. However, CT was of suboptimal quality because of sinus tachycardia (120 bpm) and so the pt underwent a coronary angiography and aortography that ruled out coronary disease, confirmed the dilatation of ascending aorta (50 mm) and showed images of penetrating atherosclerotic ulcer of the ascending aorta (Figure panel D). The pt underwent urgent transesophageal echocardiography (TOE) that confirmed the severely stenotic unicuspid AV and showed a localized type A aortic dissection (Figure Panel E, F, G). The pt underwent urgent AV and ascending aorta replacement (Figure Panel H). Learning points Chest pain and syncope are challenging symptoms in pts presenting in ED. AV pathology and aortic dissection should be always suspected and ruled out. TS is associated with multiple congenital cardiovascular abnormalities and is the most common established cause of aortic dissection in young women. 30% of Turner’s pts have congenitally AV abnormalities, and dilation of the ascending aorta is frequently associated. However, unicuspid AV is a very rare anomaly, usually stenotic at birth and requiring replacement. The presence of pericardial effusion in a pt with chest pain and syncope should raise the suspicion of aortic dissection, even if those symptoms usually accompany severe aortic stenosis. Even if CT is the gold standard imaging technique to rule out aortic dissection, the accuracy of a test is critically related to the image quality. When the suspicion of dissection is high and the reliability of the reference test is low, it’s reasonable to perform a different test to rule out the pathology. Aortography and TOE were pivotal to identify the limited dissection of the ascending aorta. Abstract P190 Figure.

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Familial Thoracic Aortic Aneurysm with Dissection Presenting as Flash Pulmonary Edema in a 26-Year-Old Man

Case Reports in Medicine ◽

10.1155/2014/842872 ◽

2014 ◽

Vol 2014 ◽

pp. 1-4 ◽

Cited By ~ 2

Author(s):

Sabry Omar ◽

Tyler Moore ◽

Drew Payne ◽

Parastoo Momeni ◽

Zachary Mulkey ◽

...

Keyword(s):

Aortic Aneurysm ◽

Aortic Dissection ◽

Thoracic Aortic Aneurysm ◽

Ascending Aorta ◽

Screening Methods ◽

Significant Past Medical History ◽

Iliac Arteries ◽

Aortic Aneurysm And Dissection ◽

History Of ◽

Chest X Ray

We are reporting a case of familial thoracic aortic aneurysm and dissection in a 26-year-old man with no significant past medical history and a family history of dissecting aortic aneurysm in his mother at the age of 40. The patient presented with cough, shortness of breath, and chest pain. Chest X-ray showed bilateral pulmonary infiltrates. CT scan of the chest showed a dissection of the ascending aorta. The patient underwent aortic dissection repair and three months later he returned to our hospital with new complaints of back pain. CT angiography showed a new aortic dissection extending from the left carotid artery through the bifurcation and into the iliac arteries. The patient underwent replacement of the aortic root, ascending aorta, total aortic arch, and aortic valve. The patient recovered well postoperatively. Genetic studies of the patient and his children revealed no mutations in ACTA2, TGFBR1, TGFBR2, TGFB2, MYH11, MYLK, SMAD3, or FBN1. This case report focuses on a patient with familial TAAD and discusses the associated genetic loci and available screening methods. It is important to recognize potential cases of familial TAAD and understand the available screening methods since early diagnosis allows appropriate management of risk factors and treatment when necessary.

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Increased aortic root diameters in patients with acromegaly

Acta Endocrinologica ◽

10.1530/eje-08-0138 ◽

2008 ◽

Vol 159 (2) ◽

pp. 97-103 ◽

Cited By ~ 22

Author(s):

Agatha A van der Klaauw ◽

Jeroen J Bax ◽

Johannes W A Smit ◽

Eduard R Holman ◽

Victoria Delgado ◽

...

Keyword(s):

Aortic Root ◽

Clinical Manifestations ◽

Left Ventricular ◽

Ascending Aorta ◽

Inactive Disease ◽

Valvular Regurgitation ◽

Healthy Controls ◽

Aortic Sinus ◽

Sinotubular Junction

ObjectiveThe clinical manifestations of acromegalic cardiomyopathy include arrhythmias, valvular regurgitation, concentric left ventricular (LV) hypertrophy, and LV systolic and diastolic dysfunction. At present, it is unknown whether acromegaly also affects the aortic root.DesignAortic root diameters were prospectively assessed in 37 acromegalic patients (18 patients with active disease and 19 with controlled disease) by conventional two-dimensional and Doppler echocardiography before, and after, an observation period of 1.9 years (range 1.5–3.0 years). Baseline parameters were compared with healthy controls.ResultsThe diameters of the aortic root at the sino-tubular junction and the ascending aorta were increased in patients with acromegaly: 30±4 vs 26±3 mm (P=0.0001) and 33±5 vs 30±4 mm (P=0.006) respectively. The diameter of the aortic root at the aortic annulus and aortic sinus were not different from controls. During follow-up, the aortic root diameters increased at the levels of the annulus and the sinotubular junction (P=0.025 and P=0.024 respectively), whereas there was no change in the diameters at the levels of the sinus and the ascending aorta during follow-up. Baseline aortic root diameters were not influenced by disease duration, current disease activity, or blood pressure. When patients with active and inactive disease were analyzed separately, only the diameter of the sinotubular junction increased in patients with inactive acromegaly during follow-up (P=0.031).ConclusionAortic root diameters are increased in patients with acromegaly compared with healthy controls.

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A novel method of treament of ascending aortic aneurysm

Cardiac Surgery and Interventional Cardiology ◽

10.31928/2305-3127-2020.4.2933 ◽

2020 ◽

pp. 29-33

Author(s):

V.B. Demyanchuk ◽

◽

V.V. Pogrebnyak ◽

O.I. Kvasha ◽

B.M. Todurov ◽

...

Keyword(s):

Surgical Treatment ◽

Aortic Aneurysm ◽

Left Ventricular ◽

Vascular Prosthesis ◽

Ascending Aorta ◽

Aortic Aneurysms ◽

Surgical Trauma ◽

Long Term Treatment ◽

Duration Of Surgery ◽

Prosthesis Fixation

The need for surgical treatment of ascending aortic aneurysms is due to a number of severe complications that occur during the natural course of the disease, such as aortic dissection and rupture. Such interventions show good immediate and long-term treatment outcomes, but they are often accompanied by high blood loss and surgical trauma, which in elderly patients with concomitant pathology can lead to serious cardiac and extracardiac complications and prolongation of treatment in general. We present a technology of external wrapping of the aorta that reduces surgical trauma while maintaining effect of operation. A clinical case of application of this technology in a 63-year-old patient hospitalized to the clinic of the Heart Institute, Ministry of Health of Ukraine, with a diagnosis of aortic insufficiency of the 3rd degree (tricuspid aortic valve), dilatation of the root and ascending aorta, tricuspid insufficiency of the 2nd degree, high pulmonary hypertension, heart failure with reduced left ventricular systolic function. The use of the proposed method has following advantages compared to the established method of fixation of the vascular prosthesis: fixation of the proximal part of the vascular prosthesis is performed using vascular suture material; elimination of the risk of damage to the aortic wall; elimination of the risk of massive bleeding from the aorta at the site of the prosthesis fixation; decreased duration of surgery. Key words: aortic aneurysm, surgical treatment, wrapping of the ascending aorta.

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INDIRECT ULTRASOUND EVALUATION OF LEFT VENTRICULAR OUTFLOW TRACT DIAMETER IMPLICATIONS FOR HEART FAILURE AND AORTIC STENOSIS SEVERITY ASSESSMENT.

10.22541/au.160615093.39506877/v1 ◽

2020 ◽

Author(s):

Gabriele Pestelli ◽

Andrea Fiorencis ◽

Valeria Pergola ◽

Giovanni Luisi ◽

Vittorio Smarrazzo ◽

...

Keyword(s):

Heart Failure ◽

Aortic Stenosis ◽

Aortic Root ◽

Left Ventricular Outflow Tract ◽

Ventricular Outflow Tract ◽

Left Ventricular ◽

Outflow Tract ◽

Regression Equation ◽

Ultrasound Evaluation ◽

Left Ventricular Outflow

Background. Whereas dependency of left ventricular outflow tract diameter (LVOTD) from body surface area (BSA) has been established and a BSA-based LVOTD formula has been derived, the relationship between LVOTD and aortic root and LV dimensions has never been explored. This may have implications for evaluation of LV output in heart failure (HF) and aortic stenosis (AS) severity. Methods. A cohort of 540 HF patients who underwent transthoracic echocardiography was divided in a derivation and validation subgroup. In the derivation subgroup (N=340) independent determinants of LVOTD were analyzed to derive a regression equation, which was used for predicting LVOTD in the validation subgroup (N=200) and compared with the BSA-derived formula. Results. LVOTD determinants in the derivation subgroup were sinuses of Valsalva diameter (SVD, beta=0.392, P<0.001), BSA (beta=0.229, P<0.001), LV end-diastolic diameter (LVEDD, beta=0.145, P=0.001), and height (beta=0.125, P=0.037). The regression equation for predicting LVOTD with the aforementioned variables (LVOTD=6.209+[0.201xSVD]+[1.802xBSA]+[0.03xLVEDD]+[0.025xHeight]) did not differ from (P=0.937) and was highly correlated with measured LVOTD (R=0.739, P<0.001) in the validation group. Repeated analysis with LV end-diastolic volume instead of LVEDD and/or accounting for gender showed similar results, whereas BSA-derived LVOTD values were different from measured LVOTD (P<0.001). Conclusion. Aortic root and LV dimensions affect LVOTD independently from anthropometric data and are included in a new comprehensive equation for predicting LVOTD. This should improve evaluation of LV output in HF and severity of AS, avoiding use of LVOT velocity-time integral alone, which can be misleading, especially when LV cavity and aortic root dimensions are abnormal.

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