A tall smoker

A 53 year old man, who was a heavy smoker, was admitted to hospital with shortness of breath at rest and a two week history of a productive cough. His medical history showed that he had never had any serious illness. He led an active life, playing cricket and football. He was slightly reticent when talking about his family. He visited his doctor, who prescribed a course of antibiotics. He failed to complete the course because he had not been sleeping well and felt “on edge.”

He later visited the emergency department and was diagnosed as having lower respiratory tract infection and anxiety attacks. He was treated accordingly. Three days after discharge, he deteriorated and entered the emergency department with acute palpitations, frothy blood tinged sputum, and frank haemoptysis.

Cardiovascular examination found a regular pulse at 108 beats/min, blood pressure of 140/72 mm Hg, and a temperature of 37.3°C. Jugular venous pressure was raised. He had no arterial bruits but a decrescendo diastolic murmur and no ankle swelling or orthopnoea.

Respiratory examination found reduced chest expansion and lung auscultation showed bilateral basal coarse crepitations. Routine biochemistry and arterial blood gases were within normal reference ranges. Both lipid profile and thyroid function tests were normal. Sputum culture found Pseudomonas aeruginosa. His chest x ray on admission is shown (fig 1). Twelve lead electrocardiography was normal.

Fig 1. Chest X-ray

Questions
Imagine you are managing this patient.

1. What further information should you seek in the history, and what would you do next?
   
2. How would you report his chest radiograph?
   
3. How would you investigate the signs of his heart failure (raised JVP, upper lobe diversion)?
   
4. With this information, what would be the possible differential diagnoses and what is the most likely diagnosis?
   
5. What other features may you find in this condition?
   
6. How would you manage the patient? What therapies could be fatal?
   
7. What advice would you give the patient? Any medico-legal issues?

Answers

1. You must get a detailed family history. His daughter (11 years of age) was relatively tall (173 cm) and had a mild functional aortic regurgitation. His wife and his sisters (40, 50, and 43 years old) were no taller than 163 cm. He remembered that his grandfather was 183 cm tall and died from a heart problem in his 40s (fig 2).

   Next treat the infection of the lower respiratory tract with oxygen at 2 l/min as necessary. Give 750 mg intravenous cefuroxime three times a day and 500 mg intravenous erythromycin twice a day. Then investigate the breathlessness further.
   

   
   
   Fig 2. Family tree

2. The chest x ray showed hyperinflated lung fields, patchy right middle lobe consolidation, and upper lobe diversion. Heart and aorta were reported normal in his notes despite the patient having a gross aortic root dilatation. Never rule this out.
   

3. Echocardiography found a gross aortic root dilatation (77.2 mm (upper limit 34.2 mm)), torrential aortic valve regurgitation and mild mitral valve regurgitation with moderate dilatation of the left ventricle. A left heart catheterisation confirmed the findings.
   

4. Possible differentials include:

   Cardiovascular

   • Congenital abnormality
   • Valvular disease (rheumatic fever, infective endocarditis, systemic lupus erythematosus)
   • Aortic root disease (hypertension, aortic dissection, Marfan’s syndrome)
   Respiratory
   • Parenchymal and interstitial disease (alveolitis, effusions, pneumonia, bronchiectasis, chronic obstructive pulmonary disease, acute respiratory distress syndrome, sarcoidosis, (cryptogenic) fibrosing alveolitis)
   • Pneumothorax, pulmonary embolus, (acute) asthma, acute pulmonary oedema
   • Extrinsic allergic alveolitis
   • Lung tumour

   Other
   

   • Thyrotoxicosis, ketoacidosis, anaemia, appetite suppressants.

   The most likely diagnosis is aortic root dilatation secondary to Marfan’s syndrome.
   

5. Skeletal—disproportionately long limbs, “spidery” fingers (arachnodactyly), pectus excavatum, scoliosis, high-arched palate, dental crowding, joint immobility

   Ocular—lens dislocation (ectopia lentis), flat cornea, cataracts, glaucoma, retinal detachment

   Cardiovascular—aortic dissection, mitral valve prolapse, dilatation of pulmonary artery or descending aorta

   Pulmonary—spontaneous pneumothorax, apical blebs seen on a chest radiograph

   Skin—stretch marks (striae atrophicae) usually seen on the lumbar back

   Other—recurrent hernias and dural ectasia (ballooning of dural sack).
   

6. Medical management—ß blockade, angiotensin converting enzyme inhibitor, or angiotensin II blockade Surgical management—Aortic root replacement with or without aortic valve replacement. Potentially fatal therapies include anticoagulation, thrombolysis and positive inotrophic and chronotrophic heart drugs. These may cause further aortic dilatation or rupture.
   

7. Avoid strenuous activities. Raised systolic blood pressures may rupture the aortic dilatation. Any concomitant hypertension should be rigorously controlled. Medicolegal issues include failure to inform patients of signs of aortic dissection, to limit strenuous exercise, and to advise patients and their family of reproductive risks of passing on Marfan’s syndrome to their children.

   Discussion
   Marfan’s syndrome is an inherited autosomal dominant connective tissue disorder transmitted with full penetrance. One in 5000 people are affected.1 People with the syndrome may be diagnosed through molecular studies, locating a mutation in chromosome 15 and other people may have had a sporadic mutation.

   Two homologous genes on chromosome 15 encode the protein fibrillin— FBN1 and FBN2. Fibrillin is one of the main constituents of microfibrils and connective tissue. It allows tropoelastin growth in elastic tissue and also acts as an anchoring structure in nonelastic tissues.²

   Some patients show isolated Marfan’s syndrome-like features but do not have the FBN1 or FBN2 mutation. This is a problem in diagnosing Marfan’s syndrome. The recognised systems implicated are ocular, neurological, skeletal, cardiovascular, respiratory, integument, and dura. Some manifestations depend on age.

   Changes in the aortic root is the main cause of mortality. Abnormal fibrillin reduces the compliance and distensibility of the aortic wall to luminal ejection forces. Consequently, progressive aortic dilatation, functional aortic regurgitation, and eventual aortic dissection and rupture ensue; their risk increases when the aortic root width exceeds 55 mm.1 Secondary consequences include mitral valve dysfunction, left ventricular dilatation, pulmonary artery dilatation and cardiac failure. Myocardial infarction is possible if coronary vessels become occluded. Deficient fibrillin deposition also reduces the structural integrity of lens zonules, ligaments, lung airways and spinal dura.

   Diagnosis
   Marfan’s syndrome is diagnosed by finding specific signs in at least two body systems (Ghent nosology), supported with immunohistological evidence on a skin sample or tracking a mutated gene running through the patient’s family. This method is not foolproof and misdiagnosis is easy. For this reason, no molecular diagnosis is currently available commercially and a diagnosis is largely subjective.

   Non-invasive imaging supplements diagnosis and in some centres remains the method of quantification of the severity of cardiovascular disease. Plain radiographs may depict medistanum widening. Transoesophageal and Doppler echocardiography will delineate heart chambers and grade valve function. It aids visualisation of the aorta and measurement of the width of the sinuses of Valsalva (essentially the aortic root). Considered to be the mainstay of diagnosis of aortic dissection, aortography’s sensitivity is not 100% and it has associated risks.

   Management
   

   ß blockers, angiotensin convering enzyme inhibitors, angiotensin II blockers
   Studies on people with Marfan’s syndrome found that ß blockers reduce the systolic impulse of blood in the aorta and reduce aortic stiffness.3 Further studies provide strong evidence that ß blockers should be considered in all people with Marfan’s syndrome, particularly younger ones.⁴

   ß blockers are not for everyone. Obvious contraindications are in patients with asthma, cardiac failure, or bradyarrythmias. Instead, calcium antagonists, angiotensin converting enzyme inhibitors, or angiotensin II blockers may prove beneficial.⁵

   Emergency surgery
   Dissection of the aortic aneurysm is an absolute indication for surgical replacement. The standard operation involves replacement of the sinuses of Valsalva and as much of the ascending aorta as possible.

   Elective root replacement
   With careful consideration of necessity, surgical risk, post-operative mortality rate, and extent of aortic regurgitation, the aortic root can be replaced by the modified Bentall (composite graft valve replacement) procedure. This involves replacement of the sinuses, the aorta up to the innominate artery, and button anastomoses of the coronary arteries. The pathological aorta is resected and haemostasis gained under direct supervision. But when should you decide to replace the aorta?
   Elective aortic root replacement is a prophylactic measure and its necessity should be assessed by aortic root widths, taken at the level of the tips of the valve leaflets (Fig 3). Current guidelines advocate prophylactic replacement when the width reaches 55 mm in adults; 50 mm in children. Surgery involves risk of aortic dissection or rupture, postoperative mortality secondary to infection, false aneurysm formation, coronary anastomotic problems, anticoagulant bleeding, or valve thrombosis. If a person does not qualify for elective replacement, the aortic root width should be regularly measured and its rate of enlargement scrutinised. Marfan’s syndrome is a differential diagnosis for shortness of breath and, more specifically, aortic regurgitation. It carries a high risk of mortality if left undiagnosed. The benefits of acquiring a thorough history and investigations were threefold. The family history showed a genetic condition affecting the peson—

   
   
   Fig 3. Aortic root widths: echocardial measurements are made
   at A, B and C, but the width at B determines the need for surgical intervention.

   Marfan’s syndrome. Early diagnosis of aortic dilatation would alert doctors not to initiate thrombolysis in a person with Marfan’s syndrome who may have instead had an acute myocardial infarction, thus preventing aortic rupture. Thirdly, medicolegal issues can be avoided.

   Current diagnosis of an aortic aneurysm is based on echocardiographical evidence and can easily be missed on a chest radiograph, as in this case. However, a clinical diagnosis of Marfan’s syndrome is more difficult due to ambiguity of current clinical diagnosis criteria and the clinical variance the syndrome exhibits.
   
   Sheraz Younas fifth year medical student, University of Manchester
   Email: sherazyounas@yahoo.co.uk
   

   Michael Coupe consultant cardiologist, Royal Oldham Hospital, Manchester
   
   
   studentBMJ 2004;12:349-392 October ISSN 0966-6494
   
   

   1. Dean JC. Management of Marfan syndrome. Heart 2002;88:97-103
   2. Hasham SN, Guo DC, Milewicz DM. Genetic basis of thoracic aortic aneurysms and dissections. Curr Opin Cardiol 2002;17:677-83.
   3. Shores J, Berger KR, Murphy EA, Pyeritz RE. Progression of aortic dilatation and the benefit of long-term beta-adrenergic blockade in Marfan’s syndrome. N Engl J Med 1994;330:1335-41.
   4. Beighton P, de Paepe A, Danks D, Finidori G, Gedde-Dahl T, Goodman R, et al. International nosology of heritable disorders of connective tissue, Berlin, 1986. Am J Med Genet 1988;29:581-94.
   5. Treasure T. Cardiovascular surgery for Marfan syndrome. Heart 2000;84:674-8.