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Right heart failure and hyperthyroidism: a neglected presentation

      To the Editor:
      Heart failure is a rare manifestation of thyrotoxicosis in previously healthy patients (
      • Klein I.
      • Ojamaa K.
      Thyrotoxicosis and the heart.
      ). Predominantly right-sided heart failure in hyperthyroidism is even more uncommon. We describe 2 such patients and discuss the mechanism.
      The first patient was a previously healthy 47-year-old woman who presented with shortness of breath and leg swelling. She was tachypneic and mildly tremulous, with a temperature of 38.5oC, an irregular heart rate of 136 beats per minute, and blood pressure of 127/70 mm Hg. Jugular venous distension, moderate ascites, and 4+ pedal edema were prominent. Thyroid gland was diffusely enlarged, without lid lag or exophthalmos. Cardiac examination revealed an apical 2/6 systolic murmur, no third heart sounds, and bibasilar rales. Electrocardiography showed atrial fibrillation. A chest radiograph showed mild pulmonary congestion and cardiomegaly. Laboratory results included a thyrotropin level <0.005 μIU/mL, a free thyroxine level of 2.5 ng/mL, and a total triiodothyronine level of 432 ng/dL. Uptake of I131 was 42% (2 hours) and 62% (24 hours). Workup for pulmonary emboli or infectious diseases was negative, pulmonary function tests were normal, and autoantibodies were not found. Echocardiography revealed normal left ventricular (LV) function, mild mitral regurgitation, and pulmonary hypertension (45 mm Hg) with tricuspid regurgitation. Symptoms resolved rapidly with furosemide, propranolol, and propylthiouracil, and the patient was discharged. However, noncompliance with the medications resulted in relapse of thyrotoxicosis and right heart failure, which resolved with reinstitution of therapy. The patient remains well.
      The second patient was a 42-year-old woman admitted for anasarca that developed over several weeks. Ten years ago, she was diagnosed with Graves’ disease and treated with propylthiouracil and propranolol. However, she remained in atrial fibrillation and dependent on both drugs. Radioactive iodine was refused. Two months before admission, she stopped taking her medications. Shortly afterward she had progressive swelling of the legs and abdomen, and weight gain. She was afebrile, with a blood pressure of 170/100 mm Hg and an irregular heart rate of 150 beats per minute. She had marked jugular venous distension, a diffusely enlarged thyroid gland, and no lid lag or exophthalmos. Lung bases were dull to percussion with decreased breath sounds. A 2/6 holosystolic murmur was heard at the apex with no third heart sounds. The abdomen was distended with massive ascites that yielded a transudative fluid. Laboratory studies revealed thyrotoxicosis (serum thyrotropin <0.01 μIU/mL).
      Electrocardiography showed atrial fibrillation. Chest radiographs showed cardiomegaly and bilateral moderate pleural effusions. Ventilation-perfusion lung scanning was normal. Chest computed tomography and echocardiography showed normal pericardium and severe pulmonary hypertension (60 mm Hg), with marked dilatation of the right atrium and ventricle, and moderate mitral and tricuspid regurgitation. There was paradoxical motion of the septum and normal LV function. Cardiac catheterization showed normal coronary arteries and confirmed the echocardiographic findings (wedge pressure, 23.2 mm Hg; right ventricular pressure, 56/18 mm Hg). Rapid volume expansion by normal saline infusion ruled out constriction. After treatment (furosemide, propranolol, propylthiouracil), she had a rapid diuresis and the anasarca resolved. She remains euthyroid and well 4 years after presentation.
      Because of the positive effects of triiodothyronine on cardiac function (
      • Gomberg-Maitland M.
      • Frishman W.H.
      Thyroid hormone and cardiovascular disease.
      ), overt heart failure in thyrotoxicosis is unexpected (
      • Klein I.
      • Ojamaa K.
      Thyrotoxicosis and the heart.
      ). Occasionally, patients develop primarily systolic heart failure because of the toxic effects of thyroid hormones on the myocardium or chronic tachycardia (
      • Klein I.
      • Ojamaa K.
      Thyrotoxicosis and the heart.
      ). In contrast, predominantly right-sided heart failure in thyrotoxic patients with preserved left ventricular function is rare (Table). It can be due to myocardial dysfunction of the right ventricle or to increased afterload. Review of the literature supports the second alternative.
      TableCharacteristics of Patients with Graves’ Disease and Right-Sided Heart Failure
      Patient Age/SexClinical PresentationPretreatment PAP
      Systolic PAP obtained by transthoracic echocardiogram except in 2 patients (references 3 and 7) in whom systolic and diastolic pulmonary pressures were obtained by cardiac catheterization.
      ,
      PVR obtained by cardiac catheterization.
      )
      OutcomePost-treatment PAP
      Systolic PAP obtained by transthoracic echocardiogram except in 2 patients (references 3 and 7) in whom systolic and diastolic pulmonary pressures were obtained by cardiac catheterization.
      ,
      PVR obtained by cardiac catheterization.
      )
      Reference
      47/FSevere right heart failure45 mm HgRapid resolutionNot doneCurrent report
      42/FAnasarca60 mm HgComplete resolution22 mm HgCurrent report
      47/MAnasarca45/18 mm Hg(78 dyne · sec · cm−5)Rapid resolutionNot done3
      62/FAnasarcaNot doneTricuspid regurgitation resolvedNot done4
      59/FAnasarca50 mm HgComplete resolution of right heart failureNot done4
      32/MEdema, severe tricuspid regurgitation27 mm HgEdema and tricuspid regurgitation resolvedNot done5
      54/MAnkle edema, distended neck veins56 mm HgComplete resolution35 mm Hg6
      46/FPeripheral edema53 mm Hg(256 dyne · sec · cm−5)Complete resolution15 mm Hg(80 dyne · sec · cm−5)7
      F = female; M = male; PAP = pulmonary artery pressure; PVR = pulmonary vascular resistance.
      * Systolic PAP obtained by transthoracic echocardiogram except in 2 patients (
      • Xenopoulos N.
      • Braden G.
      • Applegate R.
      Severe right heart failure in a patient with Graves’ disease.
      ,
      • Nakchbandi I.
      • Wirth J.
      • Inzucchi S.
      Pulmonary hypertension caused by Graves’ thyrotoxicosis.
      ) in whom systolic and diastolic pulmonary pressures were obtained by cardiac catheterization.
      PVR obtained by cardiac catheterization.
      Pulmonary artery pressure in these patients (including our patients) decreased following resolution of the hyperthyroid state (Table). The normalization of pulmonary artery pressure and resolution of all signs of heart failure with treatment of the thyrotoxicosis support a causal association. Hyperthyroid rats have been observed to develop ventricular hypertrophy affecting predominantly the right ventricle (
      • Bartosova D.
      • Chvdpil M.
      • Korecky B.
      • et al.
      The growth of the muscular and collagenous parts of the rat heart in various forms of cardiomegaly.
      ). A study of 4 thyrotoxic patients revealed that all patients had clinically “silent” pulmonary hypertension that decreased about 35% when they were euthyroid (
      • Thurnheer R.
      • Jenni R.
      • Russi E.
      • Greminger P.
      • Speich R.
      Hyperthyroidism and pulmonary hypertension.
      ). Another study reported mild pulmonary hypertension (29 ± 6 mm Hg) in 35% of patients with recently diagnosed hyperthyroidism (
      • Marvisi M.
      • Brianti M.
      • Marani G.
      • Del Borello P.
      • Bortesi M.L.
      • Guariglia A.
      Hyperthyroidism and pulmonary hypertension.
      ). Pulmonary artery pressure in these patients correlated with serum thyrotropin and free thyroxine levels (r = 0.8; P <0.001), but was normal in the euthyroid control group. The mechanism, however, remains unclear (
      • Arroliga A.C.
      • Dweik R.A.
      • Rafanan A.L.
      Primary pulmonary hypertension and thyroid disease.
      ). Nonetheless, hyperthyroidism should be considered in the differential diagnosis of right-sided heart failure with pulmonary hypertension (
      • Dougherty M.
      • Craige E.
      Apathetic hyperthyroidism presenting as tricuspid regurgitation.
      ,
      • Okura H.
      • Takatsu Y.
      High-output heart failure as a cause of pulmonary hypertension.
      ).

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        High-output heart failure as a cause of pulmonary hypertension.
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