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....................................................................................................................................................................... 4.7.1.2 Clinical presentation and natural history Although thoracic aortic disease  either aneurysms detected by screening or dissection in an emergency setting  is the principal characteristic in Marfan syndrome /HTAD, extra-aortic features in the skeletal/ocular organ system may be the key to diagnosis in some patients.

Prognosis in all HTAD entities is mainly determined by progressive dilation of the aorta, leading to aortic dissection or rupture. Prognosis varies according to the underlying genetic defect. The average age at death in untreated Marfan syndrome patients is <40 years, but can approach that of the general population in patients in whom the diagnosis is known and who are properly managed.29,194 More rare cardiovascular causes of death include heart failure and SCD.29 In Marfan syndrome, the major determinant of type A aortic dissection is the aortic root diameter with increased risk of rupture >_50 mm.195 Other risk factors include family history of aortic dissection at low diameter,193 aortic root growth rate, pregnancy, and hypertension. Increasing evidence for gene-based differences in aortic risk are emerging and need to be considered. Other parts of the aorta  or in the case of some entities, major branching vessels  may also dilate or dissect. The presence of significant aortic, tricuspid, or mitral regurgitation  usually related to valve prolapse  may lead to symptoms of ventricular volume overload. However, LV disease may also occur independently of valvular dysfunction and this may be associated with arrhythmia. Mitral valve prolapse in patients with Marfan syndrome manifests early and progresses to severe regurgitation, need for surgery, and IE earlier than idiopathic mitral valve prolapse.196

4.7.1.3 Diagnostic work-up Early identification and establishment of the correct diagnosis is critical since prophylactic surgery can prevent aortic dissection and rupture. This requires a multidisciplinary team approach with integration of clinical and genetic findings.197 The diagnosis of Marfan syndrome is based on the Ghent criteria, with aortic root aneurysm/dissection and ectopia lentis as cardinal features.198 Criteria for the other HTAD entities are less well defined. Gene panel testing is meaningful for confirmation of the diagnosis and to guide management. Mutation pick-up rate in syndromic forms is higher (>90%) than in non-syndromic entities (2030%).199 Once a pathogenic variant is identified, presymptomatic genetic screening of family members is mandatory to allow early and appropriate management. • Echocardiographic assessment of the aortic root should include measurements at the annulus, sinus, sinotubular junction, distal ascending, arch, and descending thoracic aortic levels. In adults, measurement at end diastole using the leadingto-leading edge principle is recommended. The values obtained should be corrected for the individual’s age, sex, and body size using standardized nomograms.200,201 Valvular morphology (mitral valve prolapse, BAV) and function must be assessed, as well as the presence of a PDA. LV dimension and function should be addressed according to standard recommendations. • CMR or CCT angiography from head to pelvis should be performed in every patient at baseline, providing imaging of the entire aorta and branching vessels. In addition to measuring aortic diameters, information on aortic/vertebral artery tortuosity is important for diagnostic and prognostic purposes.202,203

• Holter monitoring should be performed in symptomatic patients, as ventricular arrhythmias, conduction disturbances, and SCD can occur.

4.7.1.4 Medical therapy Although no reduction in mortality or dissection rate has been established in any trial, beta blockers remain the mainstay for medical treatment in Marfan/HTAD patients, reducing wall shear stress and aortic growth rate.204 Rigorous antihypertensive medical treatment aimed at a 24-h ambulatory systolic blood pressure <130 mmHg (110 mmHg in patients with aortic dissection) is important, although there are no data to establish outright blood pressure thresholds. ARBs did not prove to have a superior effect when compared with beta blockers or in addition to beta blockers in several trials, but may be considered as an alternative in patients intolerant to beta blockers.205,206 Medical treatment should be continued after surgery. Ongoing meta-analyses of medical treatment trials may help define subgroups  based on genetic and clinical data  who benefit from specific treatment.207 Since no medical trials have been conducted in non-Marfan HTAD, medical treatment is usually adopted from Marfan data.

4.7.1.5 Surgical treatment Indications for intervention are summarized in the Recommendations for aortic surgery in aortopathies table. Prophylactic aortic root surgery is the only definitive treatment for the prevention of aortic dissection in Marfan syndrome and related HTADs. In patients with anatomically normal aortic valves and low-grade regurgitation, a valve-sparing aortic root replacement by a Dacron prosthesis and reimplantation of the coronary arteries into the prosthesis (David procedure) has become the preferred surgical procedure with good long-term outcome, including in Marfan patients.193,208 Composite graft replacement, usually with a mechanical valve, is a more durable alternative but does require lifelong anticoagulation. The decision on which technique to use should be made on an individual basis, and patient preferences and surgical experience should be taken into account.209 Marfan and related HTADs are associated with a risk of redissection and recurrent aneurysm in the distal aorta, especially in patients with previous dissection.210,211 With improved life expectancy, these complications now occur more frequently. Open aortic surgery remains the reference method for treatment of distal aortic disease, although hybrid procedures with endovascular stenting  where proximal and distal landing is possible in a Dacron tube  could be considered in selected cases. Downloaded from academic.oup.com/eurheartj/article/42/6/563/5898606 by guest on 07 October 2026