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Telangiectasia, hereditary hemorrhagic

In medicine, hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber syndrome, is a genetic disorder that leads to vascular malformations. more...

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Signs and symptoms

HHT is characterised by telangiectasia (small vascular malformations) on the skin and mucosal linings, epistaxis (nosebleeds), and arteriovenous malformations (AVMs) in various internal organs.

Skin and mucosa telangiectasias are most remarkable on the tongue, hands/fingers, nose, lips, mouth/throat and conjunctiva.

The internal organs that can harbor AVMs often include the brain and lungs. In both, bleeding can seriously endanger life.


There are four diagnostic criteria. If three or four are met, a patient has definite HHT, while two gives a possible diagnosis:

  1. Spontaneous recidivating epistaxis
  2. Multiple teleangiectasias on typical locations (see above)
  3. Proven visceral AVM
  4. First-degree family member with HHT

When HHT is suspected, physical examination focuses on inspecting the whole skin for teleangiectasias, auscultation of the lungs and neurological examination.

Pulmonary AVMs can be anticipated by measuring oxygen levels and performing arterial blood gas (ABG) sampling. An X-ray of the chest can show susceptible lesions; in addition, low oxygen tension (<96% or a 2% decrease upon standing) or low blood oxygen levels on ABG are required for a diagnosis.


HHT is a genetic disorder by definition. It is inherited in an autosomal dominant manner.

Four forms have been described:

  • HHT1: mutation of the endoglin gene (ninth chromosome). Endoglin is a receptor of TGFβ1 (transforming growth factor beta 1) and TGFβ3. It also interacts with zyxin and ZRP-1 with its intracellular domain, to control composition of focal adhesions and regulate organization of actin filaments. This form predisposes for pulmonary AVMs and early nosebleeds.
  • HHT2: mutation in the alk1 gene (12th chromosome). Alk-1 (activin receptor-like kinase 1) is a TGFβ1 receptor. Less pulmonary AVMs and later nosebleeds, but an increased risk of pulmonary hypertension (supposedly due to altered TGFβ signalling or other related pathways which may lead to vascular malformations).
  • HHT3: a third form has been suspected to exist, but has not yet been linked to a defective gene.
  • Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome is caused by mutations in the gene SMAD4

It is possible to test patients for the presence of mutations in endoglin, ALK-1 and SMAD4. When the mutation in an affected family member has been found it is possible to test other family members and identify those people not at risk for developing the disease.


The mechanism underlying the formation of vascular malformations is not completely understood, but signalling of transforming growth factor-β1 is most likely to be involved. Possibly, connective tissue is required to support and guide proliferating blood vessels during angiogenesis, and defects in TGF-β signalling adversely affect connective tissue and matrix production.


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Multiple coronary artery-left ventricular fistulas associated with hereditary hemorrhagic telangiectasia
From CHEST, 10/1/01 by Mina A. Jacob

Coronary artery-left ventricular (LV) fistulas are extremely rare and can cause myocardial ischemia from coronary steal. We describe an elderly woman who presented with unstable angina from multiple and extensive coronary artery-LV fistulas. She also had clinical features suggestive of hereditary hemorrhagic telangiectasia (HHT). Association of coronary artery-LV fistulas with HHT has not been reported and can pose a management dilemma in view of the risks of extensive cardiopulmonary surgery and potential complications of myocardial ischemia, stroke, and brain abscess. (CHEST 2001; 120:1415-1417)

Key words: adult; coronary artery fistula; coronary steal; hereditary hemorrhagic telangiectasia. Osler-Rendu-Weber syndrome; pulmonary arteriovenous fistula

Abbreviations: CAD = coronary artery disease; CAF = coronary artery fistula; HHT = hereditary hemorrhagic telangiectasia; LV = left ventricular

Coronary artery fistula (CAFs) are rare and are found in approximately 0,1% of patients undergoing cardiac catheterization. (1) CAF involving all three major cardiac vessels and emptying into the left ventricle (arteriosystemic fistulas) are extremely uncommon. They are usually asymptomatic but can cause myocardial ischemia due to coronary steal mechanism, congestive heart failure, infective endocarditis, and rupture or thrombosis of the fistula. (2-3) We present an elderly woman admitted to the hospital with unstable angina and subsequently found to have extensive coronary artery-left ventricular (LV) fistulas, pulmonary arteriovenous shunting, and mucocutaneous telangiectasia suggesting hereditary hemorrhagic telangiectasia (HHT; Osler-Rendu-Weber syndrome). To our knowledge, CAFs associated with HHT have not been reported.


A 72-year-old woman with chronic atrial fibrillation, hypertensive heart disease, and hypothyroidism presented with recurrent episodes of classical angina associated with palpitations. Family history was significant for premature coronary artery disease (CAD) and negative for pulmonary disease, cirrhosis, or bleeding diathesis. Her medications included atenolol, digoxin, warfarin, furosemide, conjugated estrogen, and L-thyroxine. A physical examination revealed perioral and palatal telangiectasia. Cardiovascular examination findings were normal. ECG showed atrial fibrillation and LV hypertrophy. A chest radiograph revealed cardiomegaly. Cardiac enzyme levels and routine laboratory index findings were normal. In view of her high pretest likelihood of CAD, she underwent cardiac catheterization, which revealed a dominant right coronary artery, dilated tortuous coronary arteries, no significant CAD, and extensive shunting of blood between all major epicardial coronary arteries and the left ventricle. The contrast medium streamed into the left ventricle via a maze of fine vessels from the diagonal branches of the left anterior descending artery (Fig 1), midportion of the circumflex artery, and acute marginal branches of the right coronary artery. Left ventriculography showed moderate mitral regurgitation and preserved global and regional LV function. Right-heart catheterization showed moderate pulmonary hypertension (pulmonary artery pressure, 50/23 mm Hg), elevated right atrial pressure (19 mm Hg), and elevated pulmonary artery wedge pressure (26 mm Hg). Systemic arterial oxygen saturation was noted to be 89% on room air. In view of the hypoxemia, a shunt study was performed that demonstrated an anatomic right-to-left shunt of 8% and a venous admixture of 12%, which worsened in the standing position. Two-dimensional echocardiography showed concentric LV hypertrophy, moderate tricuspid regurgitation, and moderate pulmonary hypertension. Injection of agitated saline solution into a peripheral vein showed a delayed appearance of air bubbles in the left atrium with the Valsalva maneuver. The patient's symptoms improved with titration of atenolol; considering her age and the extensiveness of the fistulas, she was discharged receiving medical therapy.



This case involves an elderly woman with several risk factors for CAD, who was hospitalized for unstable angina. Cardiac catheterization revealed normal coronary arteries and multiple CAFs involving all three major coronary arteries communicating with the left ventricle. The patient's angina was most probably the result of coronary steal due to diversion of oxygen-rich blood into the LV cavity via the low-resistance fistulous channels bypassing the myocardium. (2) The delayed appearance of bubbles on the left side of the heart on contrast echocardiography was suggestive of an intrapulmonary arteriovenous shunt. (4) The worsening of the hypoxemia on standing was consistent with the presence of a shunt at the base of the lungs, which is usually the location of arteriovenous malformations in patients with HHT. (5) Standing causes preferential blood flow at the bases due to gravity and an arteriovenous communication in this location would worsen arterial hypoxemia. The additional presence of mucocutaneous telangiectasia was diagnostic of HHT in spite of absence of other features. (5) The patient also had moderate passive pulmonary hypertension and an elevated pulmonary capillary wedge pressure. This was probably due to LV diastolic dysfunction from concentric LV hypertrophy and decreased LV compliance. Poor LV diastolic compliance was due to engorgement of the LV wall from increased diastolic blood flow via the multiple CAFs. This was also the probable mechanism for the diastolic equalization of right-heart pressures. The marked dilatation and tortuosity of the coronary arteries seen on angiography (Fig 1) in our case is similar to the changes seen in the arterioles of the dermis in patients with HHT. (6) Since the basic vascular pathology in HHT is an arteriovenous malformation, (6) we believe that the CAFs were in essence coronary arteriolethebesian vein-LV cavity communications that have been described in the literature. (7) Symptomatic CAFs can be closed with coil embolization if their size and number permit transcutaneous catheterization. (8) Due to the extensive nature and small size of the CAF, our patient was managed medically.


This case illustrates a hitherto unknown combination of pulmonary arteriovenous shunt and coronary artery-LV fistulas in an elderly woman with mucocutaneous telangiectasia suggesting HHT. Cardiac vascular malformations associated with HHT have not been described before and pose a management challenge in view of the potential complications of myocardial ischemia, neurologic complications of brain abscess and stroke due to intrapulmonary shunting, and the risks of extensive cardiothoracic surgery in an elderly woman.


(1) Yamanaka O, Hobbs RE. Coronary artery anomalies in 126,595 patients undergoing coronary arteriography. Cathet Cardiovasc Diagn 1990; 21:28-40

(2) Stierle U, Giannitsis E, Sheikhzadeh A, et al. Myocardial ischemia in generalized coronary artery-left ventricular microfistulae. Int J Cardiol 1998; 63:47-52

(3) Perloff JK. Congenital coronary arterial fistula. In: Perloff JK, ed. The clinical recognition of congenital heart disease. Philadelphia, PA: W.B. Saunders Company, 1978; 576-589

(4) Oh JK, Seward JB, Tajik AJ. Contrast echocardiography. In: The echo manual. Philadelphia, PA: Lippincott Williams and Wilkins, 1999; 245-249

(5) Guttmacher AE, Marchuk DA, White RI Jr. Current concepts: hereditary hemorrhagic telangiectasia. N Engl J Med 1995; 333:918-924

(6) Braverman IM, Keh A, Jacobson BS. Ultrastructure and three-dimensional organization of the telangiectases of hereditary hemorrhagic telangiectasia. J Invest Dermatol 1990; 95:422-427

(7) Coussement P, De Geest H. Multiple coronary artery-left ventricular communications: an unusual prominent Thebesian system; a report of four cases and review of the literature. Acta Cardiol 1994; 49:165-173

(8) Dorros G, Thota V, Ramireddy K, et al. Catheter-based techniques for closure of coronary fistulae. Cathet Cardiovasc Interv 1999; 46:143-150

* From the Department of Cardiology, University of Massachusetts-Saint Vincent Hospital, Worcester, MA.

Manuscript received November 14, 2000; revision accepted March 7, 2001.

Correspondence to: Sanjeev B. Goyal, MD, Department of Cardiology, University of Massachusetts-Saint Vincent Hospital, 20 Worcester Center Blvd, Worcester, MA 01608; e-mail:

COPYRIGHT 2001 American College of Chest Physicians
COPYRIGHT 2001 Gale Group

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