PRKG1 and genetic diagnosis of early-onset thoracic aortic disease.

BACKGROUND: The 20% of thoracic aortic aneurysms and dissections independent from the main connective tissue syndromes and expected to be familial has gained importance over the past years. The more frequent pattern of inheritance of these nonsyndromic cases is autosomal dominant with incomplete penetrance and variable expression. Although many candidate genes exist, unresolved familial cases suggest still unravelled genetic variation. The main purpose of this study was to establish the genetic diagnosis of one of those. MATERIALS AND METHODS: To begin with, we applied a candidate gene approach based on both traditional and a customized massive parallel sequencing panel, followed by Illumina HiSeq 2000 whole exome sequencing of four family members affected by early-onset thoracic aortic disease and two unaffected relatives. We prioritized whole exome sequencing results based on variant location, type and frequency in general population databases and performed segregation analysis in 14 family members using traditional sequencing. RESULTS: After the negative results we obtained with candidate gene approaches, the analysis and prioritization of whole exome sequencing results brought out the heterozygote c.530G>A:p.Arg177Gln PRKG1 variant (NM_001098512), located in one of the aortic smooth muscle cell contractile apparatus genes. This candidate variant segregated with thoracic aortic disease, as it was present in seven affected and absent in five unaffected family members, further supporting its causality. CONCLUSIONS: This was the second time PRKG1 was associated with thoracic aortic disease, highlighting and reaffirming it as a strong candidate for gene-based diagnosis of nonsyndromic early-onset cases.

Usefulness of Transesophageal Echocardiography in the Evaluation of Celiac Trunk and Superior Mesenteric Artery Involvement in Acute Aortic Dissection.

Mesenteric ischemia is a serious complication of acute aortic dissection (AAD), and its early diagnosis is vital for prognosis and appropriate treatment indication. Arteries affected by this complication are the celiac trunk and superior mesenteric artery, and their evaluation is usually based on computed tomographic angiography. Transesophageal echocardiography is also a useful technique for diagnosing AAD and is essential in monitoring surgical or endovascular treatment when computed tomographic angiography is not available. However, the usefulness of transesophageal echocardiography for evaluating celiac trunk and superior mesenteric artery involvement and mesenteric ischemia mechanisms in AAD is not well established. Real-time information on mesenteric malperfusion is needed at the bedside, in primary care facilities, and in the operating room to achieve prompt diagnosis and better therapeutic management. The aims of this review are to assess the role of TEE to diagnose celiac trunk and superior mesenteric artery involvement in AAD, determine the mechanisms that can cause flow obstruction in patients with mesenteric ischemia, and analyze possible implications in the treatment of this complication.

Differences in the Area of Proximal and Distal Entry Tears at CT Angiography Predict Long-term Clinical Outcomes in Aortic Dissection.

PURPOSE: To identify entry tear variables that are related to adverse clinical events by using CT angiography (CTA) performed during the subacute phase of aortic dissection. MATERIALS AND METHODS: In this prospective study conducted from January 2000 to December 2013, participants with an aortic dissection with a patent false lumen and no comorbidities underwent CTA during the subacute phase. Participants were followed up for a survival analysis to assess the time to an adverse aortic event (AAE). The maximum aortic diameter (MAD), proximal and distal tear areas and difference between these areas, and partial false-lumen thrombosis were assessed by using Cox regression for adverse events. RESULTS: Seventy-two participants (mean age, 55 years ± 12 [standard deviation]; 55 men) were evaluated: 47 were surgically treated (type A aortic dissection) and 25 were medically treated (type B aortic dissection). Twenty-two participants had an AAE manifest during follow-up (9.22 years ± 5.78): There were 18 elective surgeries for aneurysmal degeneration, two emergent surgeries for acute aortic syndrome, and two aortic condition-related deaths. A categorical model composed of genetic aortic disease (GAD) (hazard ratio [HR], 3.4 [95% CI: 1.2, 9.9]; P = .02), MAD greater than 45 mm (HR, 6.1 [95% CI: 2.4, 15.8]; P < .001), and tear dominance (HR, 5.2 [95% CI: 2.1, 13]; P < .001), defined as an absolute tear area difference of greater than 1.2 cm2, was used to stratify participants into three risk groups: low, without any risk factors (57% [41 of 72] and 7% [three of 41] had events); intermediate, with one risk factor (31% [22 of 72] and 50% [11 of 22] had events); and high, with two or more risk factors (13% [nine of 72] and 89% [eight of nine] had events; log rank P < .001). CONCLUSION: Tear dominance demonstrated at CTA performed in the subacute phase of aortic dissection was related to long-term adverse events. Participants without GAD, dominant tears, or MAD greater than 45 mm had conditions that were safely managed with optimal medical treatment and imaging follow-up.Keywords: CT Angiography, Vascular, Aorta, Dissection Supplemental material is available for this article. © RSNA, 2021See also commentary by Fleischmann and Burris in this issue.

The current role of echocardiography in acute aortic syndrome.

Acute aortic syndrome (AAS) comprises a range of interrelated conditions caused by disruption of the medial layer of the aortic wall, including aortic dissection, intramural haematoma and penetrating aortic ulcer. Since mortality from AAS is high, a prompt and accurate diagnosis using imaging techniques is paramount. Both transthoracic (TTE) and transoesophageal echocardiography (TEE) are useful in the diagnosis of AAS. TTE should be the first imaging technique to evaluate patients with thoracic pain in the emergency room. Should AAS be suspected, contrast administration is recommended when images are not definitive. TEE allows high-quality images in thoracic aorta. The main drawback of this technique is that it is semi-invasive and the presence of a blind area that limits visualisation of the distal ascending aorta near. TEE identifies the location and size of the entry tear, secondary communications, true lumen compression and the dynamic flow pattern of false lumen. Although computed tomography (CT) is the most used imaging technique in the diagnosis of AAS, echocardiography offers complementary information relevant for its management. The best imaging strategy for appropriately diagnosing and assessing AAS is to combine CT, mainly ECG-gated contrast-enhanced CT, and TTE. Currently, TEE tends to be carried out in the operating theatre immediately before surgical or endovascular therapy and in monitoring their results. The aims of this review are to establish the current role of echocardiography in the diagnosis and management of AAS based on its advantages and limitations.

Anatomical and clinical predictors of valve dysfunction and aortic dilation in bicuspid aortic valve disease.

OBJECTIVE: Bicuspid aortic valve (BAV) is associated with early valvular dysfunction and proximal aorta dilation with high heterogeneity. This study aimed to assess the determinants of these complications. METHODS: Eight hundred and fifty-two consecutive adults diagnosed of BAV referred from cardiac outpatient clinics to eight echocardiographic laboratories of tertiary hospitals were prospectively recruited. Exclusion criteria were aortic coarctation, other congenital disorders or intervention. BAV morphotype, significant valve dysfunction and aorta dilation (≥2 Z-score) at sinuses and ascending aorta were established. RESULTS: Three BAV morphotypes were identified: right-left coronary cusp fusion (RL) in 72.9%, right-non-coronary (RN) in 24.1% and left-non-coronary (LN) in 3.0%. BAV without raphe was observed in 18.3%. Multivariate analysis showed aortic regurgitation (23%) to be related to male sex (OR: 2.80, p<0.0001) and valve prolapse (OR: 5.16, p<0.0001), and aortic stenosis (22%) to BAV-RN (OR: 2.09, p<0.001), the presence of raphe (OR: 2.75, p<0.001), age (OR: 1.03; p<0.001), dyslipidaemia (OR: 1.77, p<0.01) and smoking (OR: 1.63, p<0.05). Ascending aorta was dilated in 76% without differences among morphotypes and associated with significant valvular dysfunction. By contrast, aortic root was dilated in 34% and related to male sex and aortic regurgitation but was less frequent in aortic stenosis and BAV-RN. CONCLUSIONS: Normofunctional valves are more prevalent in BAV without raphe. Aortic stenosis is more frequent in BAV-RN and associated with some cardiovascular risk factors, whereas aortic regurgitation (AR) is associated with male sex and sigmoid prolapse. Although ascending aorta is the most commonly dilated segment, aortic root dilation is present in one-third of patients and associated with AR. Remarkably, BAV-RL increases the risk for dilation of the proximal aorta, whereas BAV-RN spares this area.

Left atrial strain: a new predictor of thrombotic risk and successful electrical cardioversion.

BACKGROUND: Left atrial deformation (LAD) parameters are new markers of atrial structural remodelling that seem to be affected in atrial fibrillation (AF) and atrial flutter (AFL). This study aimed to determine whether LAD can identify patients with a higher risk of thrombosis and unsuccessful electrical cardioversion (ECV). METHODS: Retrospective study including 56 patients with AF or AFL undergoing ECV, with previous transthoracic (TTE) and transoesophageal echocardiography (TEE) studies. Echocardiographic parameters analysed were as follows: left ventricle function, left atrium (LA) dimensions, LAD parameters (positive and negative strain peaks), left atrial appendage (LAA) filling and emptying velocities and the presence of thrombi. Strain values were analysed according to thrombotic risk and success of ECV. RESULTS: Lower mean values of peak-positive strain (PPS) in patients with prothrombotic velocities (<25 cm/s) and a higher incidence of thrombi in LAA were observed compared with those with normal velocities. Multivariate analysis revealed PPS normalised by LA maximum volume indexed by body surface area (BSA) to be associated with prothrombotic risk (odds ratio 0.000 (95% CI: 0.000-0.243), P 0.017), regardless of CHADs2VASC score. Peak-negative strain normalised by LA volumes indexed by BSA were associated with unsuccessful ECV. CONCLUSIONS: Atrial deformation parameters identify AF and AFL patients with a high risk of thrombosis and unsuccessful ECV. Therefore, these new parameters should be included in anticoagulation management and rhythm vs rate control strategies.

Stroke echoscan protocol: a fast and accurate pathway to diagnose embolic strokes.

BACKGROUND AND PURPOSE: Cardiac Echoscan is the simplified transthoracic echocardiogram focused on the main source of emboli detection in the acute stroke diagnosis (Stroke Echoscan). We describe the clinical impact related to the Stroke Echoscan protocol in our Center. METHODS: Acute stroke patients who underwent the Stroke Echoscan by a trained stroke neurologist were included (Echoscan group). All examinations were reviewed by cardiologists. The main embolic stroke etiologies were: ventricular akinesia (VA), severe aortic atheroma (AA) plaque and cardiac shunt (SHUNT). The rate of the embolic stroke etiologies and the median length of stay (LOS) were compared with a cohort of patients studied by cardiologist (Echo group). RESULTS: Eighty acute stroke patients were included. The sensitivity (S) and specificity (E) were: VA (S 98.6%, E 66.7%, k = .7), AA (S 93.3%, E 96.9%, k = .88) and SHUNT (S 100%, E 100%, k = 1), respectively. The rate of AA diagnosis was significantly higher in Echoscan group (18.8% vs. 8.9%; P = .05). Echoscan protocol significantly reduced the LOS: 6 days (IQR 3-10) versus Echo group 9 days (IQR 6-13; P < .001). CONCLUSION: The Echoscan protocol was an accurate quick test, which reduced the length of stay and increased the percentage of severe AA plaque diagnosis.

Non-obstructive prosthetic heart valve thrombosis (NOPVT): Really a benign entity?

AIMS: To assess the effectiveness of different treatment strategies in patients with non-obstructive prosthetic valve thrombosis (NOPVT) during hospitalization and long-term follow-up. METHODS: NOPVT was diagnosed by transesophageal echocardiography. Resolution was defined as the disappearance or reduction of the thrombus under anticoagulation. All cases were first managed with optimization of anticoagulation. At discharge, patients received oral anticoagulation (OAC) alone or OAC and antiplatelet therapy (double treatment). Adverse events were defined as cardiovascular death, recurrence, thromboembolic events or major bleeding. RESULTS: From 1997 to 2012, 47 patients (mean age: 65years; women: 60%) were diagnosed with NOPVT (mitral valve: 97%). Previous poor anticoagulation control was documented in 66% of patients. Twenty-one patients (45%) were treated with unfractionated heparin (UFH), especially those with thrombus size >10mm (19/21). Optimization of OAC was performed in the remaining patients. Treatment failed in 13 (27.6%) patients, mostly in those who received UFH (10/13), requiring surgery (53.8%) or fibrinolysis (30.7%). Forty-two patients survived and, at discharge, 44% of patients received OAC alone and 56% the double treatment. At follow-up (median 23months; range 0.03-116months), 59.5% of patients presented cardiovascular events, however no differences in outcome were observed with double treatment or OAC alone (p=0.385). CONCLUSIONS: NOPVT is a high-risk complication, not only during hospitalization but also during follow-up. Optimization of anticoagulation is efficient in most patients except in thrombi ≥10mm treated with UFH. The double treatment does not prevent adverse events or complications during follow-up.

[Study of the efficacy and safety of losartan versus atenolol for aortic dilation in patients with Marfan syndrome]. / Valoración de la eficacia y la seguridad del losartán frente al atenolol en la prevención de la dilatación de la aorta en el síndrome de Marfan.

INTRODUCTION AND OBJECTIVES: Marfan syndrome is an inherited disease of the connective tissue. Recent trials have indicated the use of losartan (a transforming growth factor beta inhibitor) in these patients prevents aortic root enlargement. The aim of our clinical trial is to assess the efficacy and safety of losartan versus atenolol in the prevention of progressive dilation of the aorta in patients with Marfan syndrome. METHODS: This is a phase III clinical trial conducted in two institutions. A total of 150 subjects diagnosed with Marfan syndrome, aged between 5 and 60 years, of both sexes, and who meet the Ghent diagnostic criteria will be included in the study, with 75 patients per treatment group. It will be a randomized, double blind trial with parallel assignment to atenolol versus losartan (50 mg per day in patients below 50 kg and 100 mg per day in patients over 50 kg). Both growth and distensibility of the aorta will be assessed with echocardiography and magnetic resonance. Follow-up will be 3 years. CONCLUSIONS: Efficacy of losartan versus atenolol in the prevention of progressive dilation of the aorta, improved aortic distensibility, and prevention of adverse events (aortic dissection or rupture, cardiovascular surgery, or death) will be assessed in this study. It will also show the possible treatment benefits at different age ranges and with relation to the initial level of aortic root dilation.

New concepts in the invasive and non invasive evaluation of remodelling of the right ventricle and pulmonary vasculature in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a rare fatal disease defined as a sustained elevation of pulmonary arterial pressure to more than 25 mmHg at rest, with a mean pulmonary-capillary wedge pressure and left ventricular enddiastolic pressure of less than 15 mmHg at rest. Histopathology of PAH is founded on structural modifications on the vascular wall of small pulmonary arteries characterized by thickening of all its layers. These changes, named as vascular remodelling, include vascular proliferation, fibrosis, and vessel obstruction. In clinical practice the diagnosis of PAH relies on measurements of pulmonary vascular pressure and cardiac output, and calculation of pulmonary vascular resistances. Direct evaluation of pulmonary vascular structure is not routinely performed in pulmonary hypertension since current imaging techniques are limited and since little is known about the relationship between structural changes and functional characteristics of the pulmonary vasculature. Intravascular ultrasound studies in patients with pulmonary hypertension have shown a thicker middle layer, increased wall-thickness ratio and diminished pulsatility than in control patients. Optical Coherence Tomography, a new high resolution imaging modality that has proven its superiority over intravascular ultrasound (IVUS) for the detection and characterization of coronary atherosclerotic plaque composition, may potentially be a useful technique for the in vivo study of the pulmonary arterial wall. In addition current progress in Echo Doppler technique will quantify right ventricular function with parameters independent of loading conditions and not requiring volumetric approximations of the complex geometry of the right ventricle. This would allow the in vivo study of right ventricular and pulmonary artery remodelling in PAH.

Speckle-tracking pela ecocardiografia bidimensional: aplicações clíonicas / Speckle-tracking echocardiography: clinical applications

Strain (ε) e strain rate (SR ou s-1) são índices clínicos de deformação miocárdica regional e global, que podem ser aferidos pela técnica do rastreamento de pontos (speckle tracking) através da ecocardiografia bidimensional (2D-STE). Ambos foram introduzidos e validados utilizando-se a ressonância magnética e a sonomicrometria como padrões de referência. O strain obtido com o 2D-STE apresenta várias vantagens em relação ao strain obtido com o Doppler Tecidual, principalmente uma menor variabilidade intra e inter-observador. Três padrões principais de deformação formam um eixo perpendicular no sistema de coordenadas internas do coração durante a sístole: encurtamento longitudinal, encurtamento circunferencial e espessamento radial. Aplicando-se o 2D-STE é possível aferir o strain no sentido longitudinal, circunferencial e radial da estrutura analisada, sem sofrer influência do ângulo. O 2D-STE, como ferramenta diagnóstica acurada e de fácil uso, está se desenvolvendo muito rapidamente, não só pelo seu poder diagnóstico, mas também pelo valor prognóstico das informações em várias patologias cardíacas. A possibilidade de detecção de lesão sub-clínica cardíaca tem sido uma das grandes vantagens na utilização do 2D-STE. Como todo método diagnóstico, este também tem as suas limitações, que devem ser conhecidas e respeitadas. As perspectivas futuras para o método são bastante promissoras. Embora alguns autores acreditem que o strain irá substituir a FEVE, outros acham que as informações obtidas com o 2D-STE devem ser introduzidas como um complemento e não como um substituto para os índices clínicos estabelecidos.

Strain (ε) and strain rate (SR or s-1) are clinical indices of regional myocardial deformation which can be measured by speckle tracking echocardiography and have been introduced and validated using tagged MRI and sonomicrometry. The strain measured by 2D-STE has several advantages over the strain obtained with Tissue Doppler, mainly a lower intra and inter-observer variability. Three main systolic deformation patterns form perpendicular axis in the heart’s internal coordinate system: longitudinal shortening, circumferential shortening and radial thickening. Applying the 2D-STE is possible to measure the strain in the longitudinal, circumferential, and radial axis without angle influence. The 2D-STE as a relatively user-friendly and accurate diagnostic tool is developing at a rapid pace, not only for its diagnostic power, but also because of the prognostic value of the information in various heart diseases. The possibility of detection of cardiac subclinical damage has been one of the major advantages in using the 2D-STE. Like any diagnostic method, this also has its limitations, which must be known and respected. Future prospects for the method are very promising. Although some authors believe that the strain will replace LVEF, others feel that the information obtained with the 2D-STE should be introduced as a supplement and not as a substitute for established clinical indices.