hereditary hemorrhagic telangiectasia ( hht ) , also known as rendu - osler - weber disease , is an autosomal dominant disorder characterized by atriovenous malformations ( avms ) and telangiectases in multiple organs .
the reported incidence of this disease is 1/10000 in north america but it varies between studies.1 ) the pathologic mechanism includes primary dilatation of postcapillary venules resulting in a direct connection between the arterial and venous systems , bypassing capillaries and finally forming arteriovenous shunts.2 ) the most common clinical features are nosebleeds and telangiectases on the lip , oral mucosa and hands .
high - output cardiac failure is a rare complication of hht3 ) usually caused by shunting of blood through avms in the liver .
we describe two cases of high output heart failure due to large hepatic avms , highlighting their importance in the differential diagnosis of heart failure syndromes .
a 68-year - old woman came to the hospital because of dyspnea { new york heart association ( nyha ) class 3}. on physical examination , the patient was puffy and anemic .
1 ) . her blood pressure was 100/70 mm hg , she had a heart rate of 94/min , and a respiratory rate of 22/min . cardiac examination revealed a midsystolic murmur along the sternal border and a bruit was audible over the epigastrium .
she stated that her family members ( her mother , one sister and one daughter ) also had suffered from recurrent epistaxis .
the laboratory work - up revealed hypochromic microcytic anemia ( hemoglobin 8.8 g / dl ) , normal liver function tests , and normal prothrombin time .
chest x - ray showed generalized cardiomegaly ( ct ratio 65% ) with increased pulmonary vascular markings and pulmonary edema ( fig .
2 ) . transthoracic echocardiogram showed a dilated hypercontractile left ventricle and a restrictive mitral inflow pattern ( mitral e to a ratio=1.3 , e / e=16.6 ) .
ct angiography of the abdomen showed a tortuous and dilated hepatic artery and near total replacement of liver parenchyma by engorged vascular structures with arteriovenous shunt formation ( fig .
cardiac output by right heart catheterization was 12.47 l / min , capillary wedge pressure was 22 mm hg and pulmonary artery pressure was 45/18 mm hg .
mri of the brain with contrast showed an aneurysm ( 7 mm ) in the right paraclinoid intracranial artery ( ica ) and was managed with guglielmi detachable coils ( microvention , aliso viejo , ca , usa ) .
after correction of anemia by iron supplements and treatment with angiotensin receptor blocker and diuretics , heart failure symptoms were significantly improved .
she had been diagnosed with liver cirrhosis and hypertensive heart failure 8 years previously and was intermittently managed with angiotensin receptor blocker and diuretics . from a young age
her blood pressure was 130/60 mm hg , she had a heart rate of 96/min , and a respiratory rate of 20/min . on physical examination , several telangiectases were found in both cheeks , and bounding pulses were palpated .
the liver tip was palpable below the right costal margin . a systolic murmur along the sternal border and a loud bruit over the whole upper abdomen
her laboratory work - up revealed hypochromic microcytic anema ( hemoglobin 10.6 g / dl ) , normal liver function tests , and normal prothrombin time .
chest x - ray showed generalized cardiomegaly ( ct ratio 65% ) and pulmonary edema .
transthoracic echocardiogram showed a dilated and hypertrophied left ventricle with hypercontractile left ventricular systolic function with signs of increased filling pressure and mitral inflow pattern ( e / a ratio=1.5 , deceleration time of mitral inflow e=157 msec , e / e'=12.8 ) . in order to identify the possible arteriovenous connection inside the abdomen ,
this showed a markedly engorged hepatic artery and vein with a fistulous connection between the two ( fig .
, the diagnosis of high output heart failure caused by extensive hepatic arteriovenous connections was made . for identifying the accompanying vascular abnormalities ,
chest ct angiography and cerebral mr angiography were performed and chest ct angiography showed a small avm in the right middle lobe of the lung ( fig .
4 ) . currently , her condition has been stabilized ; however , the possibility of liver transplantation in case heart failure becomes intractable has been explained to the patient .
a 68-year - old woman came to the hospital because of dyspnea { new york heart association ( nyha ) class 3}. on physical examination , the patient was puffy and anemic .
1 ) . her blood pressure was 100/70 mm hg , she had a heart rate of 94/min , and a respiratory rate of 22/min . cardiac examination revealed a midsystolic murmur along the sternal border and a bruit was audible over the epigastrium .
she stated that her family members ( her mother , one sister and one daughter ) also had suffered from recurrent epistaxis .
the laboratory work - up revealed hypochromic microcytic anemia ( hemoglobin 8.8 g / dl ) , normal liver function tests , and normal prothrombin time .
chest x - ray showed generalized cardiomegaly ( ct ratio 65% ) with increased pulmonary vascular markings and pulmonary edema ( fig .
2 ) . transthoracic echocardiogram showed a dilated hypercontractile left ventricle and a restrictive mitral inflow pattern ( mitral e to a ratio=1.3 , e / e=16.6 ) .
ct angiography of the abdomen showed a tortuous and dilated hepatic artery and near total replacement of liver parenchyma by engorged vascular structures with arteriovenous shunt formation ( fig .
cardiac output by right heart catheterization was 12.47 l / min , capillary wedge pressure was 22 mm hg and pulmonary artery pressure was 45/18 mm hg .
mri of the brain with contrast showed an aneurysm ( 7 mm ) in the right paraclinoid intracranial artery ( ica ) and was managed with guglielmi detachable coils ( microvention , aliso viejo , ca , usa ) .
after correction of anemia by iron supplements and treatment with angiotensin receptor blocker and diuretics , heart failure symptoms were significantly improved .
she had been diagnosed with liver cirrhosis and hypertensive heart failure 8 years previously and was intermittently managed with angiotensin receptor blocker and diuretics . from a young age
her blood pressure was 130/60 mm hg , she had a heart rate of 96/min , and a respiratory rate of 20/min . on physical examination ,
the liver tip was palpable below the right costal margin . a systolic murmur along the sternal border and a loud bruit over the whole upper abdomen
her laboratory work - up revealed hypochromic microcytic anema ( hemoglobin 10.6 g / dl ) , normal liver function tests , and normal prothrombin time .
chest x - ray showed generalized cardiomegaly ( ct ratio 65% ) and pulmonary edema .
transthoracic echocardiogram showed a dilated and hypertrophied left ventricle with hypercontractile left ventricular systolic function with signs of increased filling pressure and mitral inflow pattern ( e / a ratio=1.5 , deceleration time of mitral inflow e=157 msec , e / e'=12.8 ) . in order to identify the possible arteriovenous connection inside the abdomen ,
this showed a markedly engorged hepatic artery and vein with a fistulous connection between the two ( fig .
, the diagnosis of high output heart failure caused by extensive hepatic arteriovenous connections was made . for identifying the accompanying vascular abnormalities ,
chest ct angiography and cerebral mr angiography were performed and chest ct angiography showed a small avm in the right middle lobe of the lung ( fig .
4 ) . currently , her condition has been stabilized ; however , the possibility of liver transplantation in case heart failure becomes intractable has been explained to the patient .
hereditary hemorrhagic telangiectasia or osler - weber - rendu disease , characterized by telangiectases and avm in multiple organs is a rare disease with autosomal dominant transmission.4 ) the classic triad is recurrent epistaxis , mucocutaneous telangiectasia , and familial occurrence . the diagnosis of hht is confirmed if any three of the following four criteria are met : 1 ) recurrent epistaxis ; 2 ) multiple telangiectasias ; 3 ) presence of visceral lesions ( in the gastrointestinal tract , lung , liver , brain ) ; 4 ) first degree family history of hht.4 ) hepatic involvement in hht has been reported in 74% of patients with ct of the abdomen . but liver involvement tends to be asymptomatic in majority of cases and the frequency of symptomatic hepatic involvement is less than 10%.1 ) although heart failure secondary to the hyperdynamic circulatory situation caused by arteriovenous fistulas is a well - known clinical entity , the clinical presentation of heart failure is very rare in hht.3 ) the physiological mechanism in high output heart failure is of reduced systemic vascular resistance .
this leads to activation of the renin - angiotensin - aldosterone system , causing salt and water retention .
the shunting of blood through the avms , especially in the liver leads to maldistribution of cardiac output . in order to supply blood to vital organs , cardiac output
is increased with elevated stroke volume and heart rate , leading to high output heart failure .
a high cardiac output has been described as being > 8 l / min or a cardiac index > 3.9 l / min / m.5 ) right heart catheterization in our case 1 demonstrated a markedly increased cardiac output of 12.47 l / min .
reported cases of right - heart catheterization in patients with symptomatic hepatic avms have calculated shunts of 24% to 58% of the cardiac output.6 ) the echocardiography usually shows compensatory left ventricular dilatation and left ventricular hypertrophy , but preserved or high left ventricular systolic function .
5 ) high output heart failure could be presented as a diastolic dysfunction.7 ) echocardiographic findings in our cases were consistent with those of the previous reports .
in contrast to low output heart failure , clinical trial data regarding treatment of high output heart failure are lacking .
diuretics are the mainstay of treatment in high output heart failure , especially with symptoms of volume overload .
the patients in the two above mentioned cases were treated with angiotensin receptor blocker and diuretics .
there have been scattered experiences with transfemoral embolization,8 ) surgical ligation of the feeding vessels9 ) in symptomatic patients . however , in intractable patients , liver transplantation10 ) has been the standard treatment .
recently , treatment with bevacizumab11)-the anti - vascular endothelial growth factor has been reported to be effective in heart failure patients with hht by slowing the progression of vascular malformations .
cerebral avms are present in 5% to 23% of patients with hht with intracranial hemorrhage rates of 0.41% to 2% per year.1 ) but the association between intracerebral aneurysm and hht has not been reported in the literature .
thus , the possibility of an incidental coexistence of intracerebral aneurysm with hht is likely .
reported cases with cerebral involvement were managed by neurovascular surgery , embolotherapy , and stereotactic radiosurgery.12)13 ) the case of the woman with a cerebral aneurysm in the right paraclinoid ica was treated successfully with guglielmi detachable coils .
three hht genes ( endoglin , activin a receptor type ii - like 1 , smad4 ) have been identified to date , and several others are suspected.12 ) genetic studies were not performed in our cases due to economic problems .
when a proband is found , it is necessary to take a careful family history in order to detect possible hht in multiple relatives .
although the disease may be easily suspected when history and clinical manifestations are typical , there are some cases like those in our study that were initially misdiagnosed
. the most important first step towards managing hht is clinical suspicion of hht and early diagnosis by detailed history taking and physical examination , because the first presentation of this disease can be a critical condition such as massive hemoptysis , brain hemorrhage . in conclusion , we present here two patients of hht who presented with high output heart failure .
high output heart failure was controlled by medical management with some clinical improvement , but a careful follow - up may be necessary to detect developing cerebral or pulmonary avms
. clinical suspicion of hht based on detailed history taking and physical examination is essential for early detection and proper management of heart failure associated with hht .
 high - output cardiac failure is a rare complication of hereditary hemorrhagic telangiectasia ( hht ) usually caused by shunting of blood through atriovenous malformations ( avms ) in the liver . 
 we describe two cases of high output heart failure due to large hepatic avms . 
 clinical suspicion of hht based on detailed history taking and physical examination is essential for early detection and proper management of heart failure associated with hht . 
Introduction
Case
Case 1
Case 2
Discussion