This Article Abstract Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Siu, C.-W. Articles by Tse, H.-F. Search for Related Content PubMed PubMed Citation Articles by Siu, C.-W. Articles by Tse, H.-F. Related Collections Thyroid Cardiovascular Endocrinology

Hemodynamic Changes in Hyperthyroidism-Related Pulmonary Hypertension: A Prospective Echocardiographic Study

Cardiology (C.-W.S., X.-H.Z., C.Y., C.-P.L., H.-F.T.) and Metabolic and Endocrinology (A.W.C.K.) Divisions, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China

Address all correspondence and requests for reprints to: Hung-Fat Tse, M.D., Cardiology Division, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China. E-mail: hftse{at}hkucc.hku.hk.

	Abstract

Top Abstract Introduction Patients and Methods Results Discussion References

 
Context: Recent reports suggest an association between hyperthyroidism and pulmonary hypertension (PHT), although the potential mechanisms and clinical implications remain unclear.

Objective: Our objective was to determine the prevalence of PHT related to hyperthyroidism and the associated hemodynamic changes and outcome.

Methods and Results: We performed serial echocardiographic examinations in 75 consecutive patients with hyperthyroidism (43 ± 2 yr, 47 women) to estimate pulmonary artery systolic pressure (PASP), cardiac output (CO), total vascular resistance (TVR), and left ventricular (LV) filling pressure. Examinations were performed at baseline and 6 months after initiation of antithyroid treatment. Results were compared with 35 age- and sex-matched healthy controls. All hyperthyroid patients had normal LV systolic function, and 35 patients (47%) had PHT with PASP of at least 35 mm Hg. There were no significant differences in the clinical characteristics of hyperthyroid patients with or without PHT (all P > 0.05). Nonetheless, those with PHT had significantly higher CO, PASP, peak transmitral early diastolic flow velocity (E), and ratio of E to early diastolic mitral annular velocity (E') compared with those without PHT and controls (all P < 0.05). Hyperthyroid patients with PHT also had significantly lower TVR than controls (P < 0.05). Among the 35 hyperthyroid patients with PHT, 25 (71%) had pulmonary arterial hypertension (PAH) with normal E/E', and 10 (29%) had pulmonary venous hypertension (PVH) with elevated E/E'. Hyperthyroid patients with PAH had a significantly higher CO and a lower TVR compared with those with PVH. In contrast, hyperthyroid patients with PVH had lower E' and a higher E/E' ratio compared with those with PAH. These hemodynamic abnormalities and PHT were reversible in patients with PAH or PVH after restoration to a euthyroid state.

Conclusion: In patients with hyperthyroidism and normal LV systolic function, up to 47% had PHT due to either PAH with increased CO (70%) or PVH with elevated LV filling pressure (30%). Most importantly, hyperthyroidism-related PHT was largely asymptomatic and reversible after restoration to a euthyroid state.

	Introduction

Top Abstract Introduction Patients and Methods Results Discussion References

 
HYPERTHYROIDISM IS A common metabolic disorder that is associated with prominent cardiovascular manifestations (1, 2, 3). Its hyperdynamic circulatory effect is due to a marked reduction in peripheral vascular resistance and an increased total blood volume and heart rate (4, 5, 6). Hyperthyroidism can consequently exacerbate preexisting cardiac disease or cause de novo cardiovascular abnormalities, such as atrial fibrillation and heart failure (3). Recent studies also suggest a potential link between hyperthyroidism and pulmonary hypertension (PHT) (7, 8, 9, 10). In contrast to idiopathic primary PHT or secondary PHT due to autoimmune vascular disease, hyperthyroidism-related PHT appears to have a good prognosis; pulmonary arterial pressure often normalizes after successful treatment of hyperthyroidism (11, 12, 13). To our knowledge, the prevalence and clinical outcome of hyperthyroidism-related PHT have not been systematically addressed. In addition, the potential pathogenic mechanisms of hyperthyroidism-related PHT remain unclear (14).

Recent advances in echocardiographic technology enable accurate noninvasive assessment of cardiac hemodynamic parameters related to PHT, including pulmonary arterial systolic pressure (PASP), cardiac output (CO), and pulmonary capillary wedge pressure (15, 16, 17, 18). The purpose of this study was thus to investigate the natural course and clinical outcome of PHT related to hyperthyroidism and to determine the serial hemodynamic changes of PHT related to hyperthyroidism using echocardiographic measurements.

	Patients and Methods

Top Abstract Introduction Patients and Methods Results Discussion References

 
Patients and settings

This prospective study included consecutive patients referred to our Thyroid Outpatient Clinic from March to June 2004 for treatment of hyperthyroidism. Patients were excluded if they had any of the following: preexisting cardiovascular disease, including significant valvular heart disease, coronary artery disease, dilated or hypertrophic cardiomyopathy, and congestive heart failure; history of pulmonary thromboembolism or significant pulmonary disease; autoimmune connective tissue disease; use of anorectic agents; symptomatic heart failure at presentation; or prescribed antithyroid therapy and/or ß-adrenergic blockers at the time of referral. Demographic data were prospectively collected and included history of smoking, drug history, electrocardiography (ECG), chest x-ray, and laboratory results, including serum free T₄ level, TSH level, antithyroglobulin antibody titer, and antimicrosomal antibody titer. Data were recorded at presentation and at the 6-month follow-up. Hyperthyroidism was diagnosed in the presence of a serum free T₄ level more than 23 pmol/liter and concomitant suppressed TSH level less than 0.03 pmol/liter. A diagnosis of Graves’ disease was based on the clinical presentation of hyperthyroidism, usually in the presence of a diffuse goiter with or without thyroid eye signs and positive immunological markers (3).

Thirty-five age- and sex-matched controls were selected from a group of healthy subjects referred for health or preemployment screening. Subjects with preexisting cardiac, pulmonary, or thyroid disorders or abnormal cardiovascular physical examination or investigations, including ECG and echocardiogram, were excluded.

The study protocol was approved by the local research ethics committee, and informed consent was obtained from all participants.

Echocardiographic examination

Detailed transthoracic echocardiography examination was performed at presentation before initiation of antithyroid therapy and at the 6-month follow-up. Two-dimensional, M-mode, Doppler flow, and tissue Doppler imaging studies were performed in all subjects using the System V machine (Vingmed, General Electric, Milwaukee, WI) with a 3.5-MHz transducer. Two-dimensional and M-mode measurements were performed according to the recommendations of the American Society of Echocardiography (19). Valvular regurgitation was classified as mild, moderate, or severe using a semiquantitative method (20). A standard Doppler echocardiographic method was used to estimate CO (21). For the calculation of CO, an average of five consecutive heart beats during sinus rhythm, or an average of 13 beats in case of atrial fibrillation, was obtained (22). Simultaneous blood pressure measurements were made with a calibrated noninvasive semiautomatic device (Dinamap 1846XT; Critikon Corp., Tampa, FL) during the determination of CO. Total vascular resistance (TVR) in dyne-sec/cm^–5 was calculated using the following formula: TVR = [80 x (mean arterial blood pressure/CO)].

For the calculation of PASP, right ventricular systolic pressure was determined using continuous-wave Doppler echocardiography and added to mean right atrial pressure as described previously (21). Right atrial pressure was estimated with the caval index that measures the respiratory collapse of the inferior vena cava (23). PHT was defined as PASP of at least 35 mm Hg. Based on the Venice clinical classification for PHT (24, 25), an additional assessment of pulmonary capillary wedge pressure may allow distinction between pulmonary arterial hypertension (PAH) and pulmonary venous hypertension (PVH) in patients with concomitant left heart disease. Pulmonary capillary wedge pressure was estimated using a tissue Doppler imaging technique that determines the ratio of the transmitral early diastolic flow velocity (E) to the early diastolic mitral annular velocity (E') (15). In patients with a normal left ventricular (LV) ejection fraction (50%), a ratio of E/E' of more than 11 is suggestive of elevated pulmonary capillary wedge pressure; in cases of impaired LV ejection fraction (<50%), a ratio of E/E' of more than 15 was considered elevated pulmonary capillary wedge pressure (15, 16, 17, 18). Using these data, patients with PHT were then further classified as having either PAH (normal E/E') or PVH (high E/E').

All echocardiographic examinations were performed by a single experienced operator (C.-W.S). All digital images were stored on optical diskettes for subsequent off-line analysis using a computer workstation (EchoPAC; GE Medical) by another operator (X.-H.Z.) blinded to the clinical status of study subjects.

Follow-up

All patients were assessed every 2–3 months in the outpatient clinic. A repeat clinical evaluation, ECG, laboratory measurements, and transthoracic echocardiography were performed 6 months after initiation of treatment of hyperthyroidism (antithyroid drug or radioactive ¹³¹I).

Statistical analysis

Continuous variables are expressed as mean ± 1 SEM. Statistical comparisons were performed with Student’s t test or Fisher’s exact test, as appropriate. Changes in continuous variables at baseline and 6-month follow-up were analyzed with paired Student’s t test. Calculations were performed using SPSS software (version 10.0): a P value < 0.05 was considered statistically significant.

	Results

Top Abstract Introduction Patients and Methods Results Discussion References

 
Study population

A total of 75 consecutive patients with confirmed hyperthyroidism were studied. The mean age was 43 ± 2 yr, and most were female (63%). All patients had suppressed TSH (<0.03 pmol/liter) and elevated free T₄ level (mean 66 ± 4 pmol/liter). An elevated antithyroperoxidase antibody titer and antithyroglobulin antibody titer was detected in 29 patients (39%) and in 15 patients (20%), respectively. Graves’ disease was the underlying etiology in 30 patients (40%) and multinodular goiter in 45 (60%). No patient had symptoms of congestive heart failure at presentation; ECG revealed the presence of atrial fibrillation in eight patients (11%) and sinus tachycardia in 16 (21%) (Table 1).

There were no significant differences in baseline clinical characteristics between patients with hyperthyroidism and controls (Table 1). As expected, patients with hyperthyroidism had a significantly higher serum level of free T₄ and a lower prevalence of normal sinus rhythm compared with controls.

Doppler echocardiographic examination revealed PHT in 35 patients (47%) with hyperthyroidism. There were no significant differences in baseline clinical characteristics, prescribed medication, or prevalence of Graves’ disease between hyperthyroid patients with or without PHT. Hyperthyroid patients with PHT nonetheless had a significantly higher serum level of free T₄ than those without (Table 1).

Echocardiographic examination revealed normal LV ejection fraction of more than 60% in all patients with hyperthyroidism and controls. There were no significant differences in the LV end-diastolic dimension, LV ejection fraction, and left atrial diameter between hyperthyroid patients with or without PHT (Table 2). Control subjects nonetheless had significantly smaller LV end-diastolic dimension and left atrial diameter, and a larger LV ejection fraction compared with hyperthyroid patients with PHT but not compared with those without (Table 2). Hyperthyroid patients with PHT had significantly higher CO, PASP, peak E, and E/E' ratio compared with those patients without PHT and controls. Hyperthyroid patients with PHT also had significantly lower TVR than controls (Table 2). Mild and moderate mitral regurgitation was detected in 12 patients and one patient with hyperthyroidism (17%), respectively. Although there was no difference in the prevalence of mitral regurgitation between hyperthyroid patients with and without PHT, the prevalence of mitral regurgitation was higher compared with that in control subjects (Table 2). There were no differences in the indexes of diastolic LV function, including the ratio of E to peak transmitral late diastolic flow velocity (A), deceleration time, isovolumic relaxation time, and E' between hyperthyroid patients with or without PHT and controls (Table 2).

Among those 35 hyperthyroid patients with PHT, 25 (71%) had PAH with normal E/E', and 10 (29%) had PVH with elevated E/E'. There were no significant differences in clinical characteristics between hyperthyroid patients with PAH and PVH (Table 3). The mean PASP in hyperthyroid patients with PAH and PVH was 48 ± 1.3 and 49 ± 2.6 mm Hg, respectively (Table 4; P = 0.78). Other echocardiographic parameters including LV end-diastolic diameter, left atrial diameter, and LV ejection fraction did not differ significantly between hyperthyroid patients with PAH and PVH (Table 4). Hyperthyroid patients with PAH nonetheless had a significantly higher CO and a lower TVR compared with those with PVH (Table 4). In contrast, hyperthyroid patients with PVH had lower E' and higher E/E' ratio compared with those with PAH.

Antithyroid medications (carbimazole or propylthiouracil) were prescribed to 65 patients (87%) and another 10 (13%) underwent radioactive iodine as primary treatment of hyperthyroidism. In those 35 hyperthyroid patients with PHT, 27 (77%) were treated with carbimazole, three with propylthiouracil (9%), and five (14%) with radioactive iodine. All patients treated with radioactive iodine had Graves’ disease. There was no difference in the treatment options between patients with or without PHT (all P > 0.05). Follow-up echocardiography was performed in 19 of 25 patients (76%) with PAH and eight of 10 patients (80%) with PVH who had achieved a clinically and biochemically euthyroid state at 6 months.

In hyperthyroid patients with PAH, the mean PASP decreased from 47 ± 2 to 34 ± 2 mm Hg (P < 0.01; Fig. 1A). This reduction after achieving a euthyroid state was associated with a decrease in CO from 6.1 ± 0.5 to 4.5 ± 0.3 liters/min (Fig. 1B; P < 0.01) and heart rate from 89 ± 5 to 77 ± 4 beats/min (P = 0.01) and an increase in TVR from 1319 ± 96 to 1710 ± 108 dynes-sec/cm^–5 (Fig. 1C; P < 0.01). There was also a significant positive correlation of the percent change in PASP with the percent change in CO from the hyperthyroid state to euthyroid state (r = 0.70; P < 0.01, Fig. 2A). There was no significant change in E/E' ratio (Fig. 1D; P > 0.05).

View larger version (19K): [in this window] [in a new window]   FIG. 1. Serial changes in PASP (A), CO (B), TVR (C), and E/E' ratio (D) in hyperthyroid patients with pulmonary hypertension due to PAH and PVH at baseline and 6 months after initiation of antithyroid therapy.

View larger version (13K): [in this window] [in a new window]   FIG. 2. A, Relationship between the percent change in PASP and percent change in CO from hyperthyroid to euthyroid state in patients with PAH; B, relationship between the percent change in PASP and percent change in E/E' from hyperthyroid to euthyroid state in patients with PVH.

	Discussion

Top Abstract Introduction Patients and Methods Results Discussion References

Although hyperthyroidism has been proposed as a reversible cause of PHT, there are limited data on its incidence and pathogenesis (7, 9, 10). Previous studies (9) show that up to 41% of patients with hyperthyroidism have elevated PASP (>35 mm Hg), although the potential mechanism of PHT was not explored. Consistent with this finding, our study shows that up to 47% of unselected hyperthyroid patients had asymptomatic PHT, confirming that PHT is a common but clinically unrecognized condition in hyperthyroid patients.

It has been postulated that the pathogenesis of PHT in hyperthyroid patients is similar to that of other autoimmune diseases related to PTH (26). This hypothesis appears plausible because a substantial proportion of patients with hyperthyroidism have Grave’s disease. This is further supported by the high prevalence of autoimmune thyroid disorders in patients with primary PHT (14). PHT in hyperthyroid patients nonetheless does not occur exclusively in subjects with Graves’ disease but is also observed in patients with multinodular goiter (7, 9, 10). In this study, there was also no significant difference in the prevalence of positive autoimmune antibodies between patients with or without PHT. PHT related to hyperthyroidism also resolved after successful antithyroid treatment regardless of the underlying etiology of hyperthyroidism. These findings do not suggest that the underlying autoimmune process contributes to the pathogenesis of PHT related to hyperthyroidism (11, 12, 13).

We observed no significant differences in the clinical characteristics between patients with and without PHT. There were no significant differences in the LV ejection fraction and diastolic indexes that could explain the occurrence of PHT. Merce et al. (9) reported moderate mitral regurgitation in 13% of patients with hyperthyroidism. Likewise, we observed mild to moderate mitral regurgitation in 13 of 75 (17%). There was no significant difference in the prevalence of mitral regurgitation between patients with and without PHT.

Our study suggests that cardiovascular abnormalities related to hyperthyroidism play an important role in the mechanism of PHT. Hyperthyroid patients with PHT had a significantly higher serum free T₄ level compared with patients without PHT. They also had increased CO and decreased TVR compared with controls. The marked fall in TVR in patients with hyperthyroidism is probably due to the direct effect of thyroid hormone on vascular smooth muscle cells (26). This reduction in TVR as well as the direct inotrophic and chronotrophic effects of thyroid hormone lead to increased CO.

In this study, PHT was related to the occurrence of either PAH (71%) or PVH (29%) related to hyperthyroidism. Although there were no significant differences in the clinical characteristics between patients with PAH and PVH, they had different cardiovascular hemodynamic changes related to PHT. Patients with PAH had significantly lower TVR and higher CO than patients with PVH. In patients with PAH, the lack of a vasodilatory response of the pulmonary vasculature to thyroid hormone (27) might not allow the pulmonary circulation to accommodate the increased CO and thus result in an elevated PASP. In contrast, patients with PVH had significantly lower E' than patients with PAH, suggesting early diastolic dysfunction. Although the mechanisms remain unclear, recent studies demonstrate that prolonged subclinical hyperthyroidism is associated with LV diastolic dysfunction (28). Patients with PVH also tend to be older than patients with PAH. This might contribute to the abnormal LV diastolic function due to aging. Impaired LV diastolic function can lead to elevated LV filling pressure, as reflected by an increased E/E', and thus cause PHT.

This study has several limitations. First, invasive hemodynamic assessment was not performed, and precise measurements of CO, TVR, and LV filling pressure were not obtained. Hemodynamic parameters were based on estimates from echocardiographic assessment. Second, we did not routinely perform additional investigations, such as markers for autoimmune connective tissue disease or imaging for pulmonary thromboembolism to exclude secondary PHT. Patients with established causes of secondary PHT were nonetheless excluded from study, and PHT resolved in all patients after successful treatment of hyperthyroidism. Third, although patients with PHT reported no symptoms of heart failure, the impact of the development of PHT on exercise capacity was not objectively assessed.

In conclusion, PHT is a frequent complication of hyperthyroidism but usually resolves after successful treatment of hyperthyroidism.

	Footnotes

 
Disclosure Summary: The authors have nothing to disclose.

First Published Online February 27, 2007

Abbreviations: A, Peak transmitral late diastolic flow velocity; CO, cardiac output; E, peak transmitral early diastolic flow velocity; E', early diastolic mitral annular velocity; ECG, electrocardiography; LV, left ventricular; PAH, pulmonary arterial hypertension; PASP, pulmonary arterial systolic pressure; PHT, pulmonary hypertension; PVH, pulmonary venous hypertension; TVR, total vascular resistance.

Received August 25, 2006.

Accepted February 16, 2007.

	References

Top Abstract Introduction Patients and Methods Results Discussion References

 

1. Polikar R, Burger AG, Scherrer U, Nicod P 1993 The thyroid and the heart. Circulation 87:1435–1441[Abstract/Free Full Text]
2. Klein I, Ojamaa K 2001 Thyroid hormone and the cardiovascular system. N Engl J Med 344:501–509[Free Full Text]
3. Siu CW, Yeung CY, Lau CP, Kung A, Tse HF, Incidence, clinical characteristics and outcome of congestive heart failure as the initial presentation in patients with primary hyperthyroidism. Heart, in press
4. Feldman T, Borow KM, Sarne DH, Neumann A, Lang RM 1986 Myocardial mechanics in hyperthyroidism: importance of left ventricular loading conditions, heart rate and contractile state. J Am Coll Cardiol 7:967–974[Abstract]
5. Kahaly GJ, Kampmann C, Mohr-Kahaly S 2002 Cardiovascular hemodynamics and exercise tolerance in thyroid disease. Thyroid 12:473–481[CrossRef][Medline]
6. Klein I 1990 Thyroid hormone and the cardiovascular system. Am J Med 88:631–637[CrossRef][Medline]
7. Thurnheer R, Jenni R, Russi EW, Greminger P, Speich R 1997 Hyperthyroidism and pulmonary hypertension. J Intern Med 242:185–188[CrossRef][Medline]
8. Marvisi M, Brianti M, Marani G, Del Borello R, Bortesi ML, Guariglia A 2002 Hyperthyroidism and pulmonary hypertension. Respir Med 96:215–220[CrossRef][Medline]
9. Merce J, Ferras S, Oltra C, Sanz E, Vendrell J, Simon I, Camprubi M, Bardaji A, Ridao C 2005 Cardiovascular abnormalities in hyperthyroidism: a prospective Doppler echocardiographic study. Am J Med 118:126–131[CrossRef][Medline]
10. Marvisi M, Zambrelli P, Brianti M, Civardi G, Lampugnani R, Delsignore R 2006 Pulmonary hypertension is frequent in hyperthyroidism and normalizes after therapy. Eur J Intern Med 17:267–271[CrossRef][Medline]
11. Agraou B, Tricot O, Strecker A, Bresson R, Leroy F, Langlois P, Lauwerier B, Dujardin JJ 1996 [Hyperthyroidism associated with pulmonary hypertension]. Arch Mal Coeur Vaiss 89:765–768 (French)[Medline]
12. Nakchbandi IA, Wirth JA, Inzucchi SE 1999 Pulmonary hypertension caused by Graves’ thyrotoxicosis: normal pulmonary hemodynamics restored by ¹³¹I treatment. Chest 116:1483–1485[CrossRef][Medline]
13. Lozano HF, Sharma CN 2004 Reversible pulmonary hypertension, tricuspid regurgitation and right-sided heart failure associated with hyperthyroidism: case report and review of the literature. Cardiol Rev 12:299–305[CrossRef][Medline]
14. Chu JW, Kao PN, Faul JL, Doyle RL 2002 High prevalence of autoimmune thyroid disease in pulmonary arterial hypertension. Chest 122:1668–1673[CrossRef][Medline]
15. Nagueh SF, Middleton KJ, Kopelen HA, Zoghbi WA, Quinones MA 1997 Doppler tissue imaging: a noninvasive technique for evaluation of left ventricular relaxation and estimation of filling pressures. J Am Coll Cardiol 30:1527–1533[Abstract]
16. Rivas-Gotz C, Manolios M, Thohan V, Nagueh SF 2003 Impact of left ventricular ejection fraction on estimation of left ventricular filling pressures using tissue Doppler and flow propagation velocity. Am J Cardiol 91:780–784[CrossRef][Medline]
17. Dokainish H 2004 Tissue Doppler imaging in the evaluation of left ventricular diastolic function. Curr Opin Cardiol 19:437–441[CrossRef][Medline]
18. Dokainish H, Zoghbi WA, Lakkis NM, Al-Bakshy F, Dhir M, Quinones MA, Nagueh SF 2004 Optimal noninvasive assessment of left ventricular filling pressures: a comparison of tissue Doppler echocardiography and B-type natriuretic peptide in patients with pulmonary artery catheters. Circulation 109:2432–2439[Abstract/Free Full Text]
19. Cheitlin MD, Armstrong WF, Aurigemma GP, Beller GA, Bierman FZ, Davis JL, Douglas PS, Faxon DP, Gillam LD, Kimball TR, Kussmaul WG, Pearlman AS, Philbrick JT, Rakowski H, Thys DM, Antman EM, Smith Jr SC, Alpert JS, Gregoratos G, Anderson JL, Hiratzka LF, Hunt SA, Fuster V, Jacobs AK, Gibbons RJ, Russell RO 2003 ACC/AHA/ASE 2003 guideline update for the clinical application of echocardiography. Summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ASE Committee to Update the 1997 Guidelines for the Clinical Application of Echocardiography). Circulation 108:1146–1162[Free Full Text]
20. Helmcke F, Nanda NC, Hsiung MC, Soto B, Adey CK, Goyal RG, Gatewood Jr RP 1987 Color Doppler assessment of mitral regurgitation with orthogonal planes. Circulation 75:175–183[Abstract/Free Full Text]
21. Evangelista A, Garcia-Dorado D, Garcia del Castillo H, Gonzalez-Alujas T, Soler-Soler J 1995 Cardiac index quantification by Doppler ultrasound in patients without left ventricular outflow tract abnormalities. J Am Coll Cardiol 25:710–716[Abstract]
22. Dubrey SW, Falk RH 1997 Optimal number of beats for the Doppler measurement of cardiac output in atrial fibrillation. J Am Soc Echocardiogr 10:67–71[CrossRef][Medline]
23. Kircher BJ, Himelman RB, Schiller NB 1990 Noninvasive estimation of right atrial pressure from the inspiratory collapse of the inferior vena cava. Am J Cardiol 66:493–496[CrossRef][Medline]
24. Rubin LJ 2004 Diagnosis and management of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest 126:7S–10S
25. Galie N, Torbicki A, Barst R, Dartevelle P, Haworth S, Higenbottam T, Olschewski H, Peacock A, Pietra G, Rubin LJ, Simonneau G, Priori SG, Garcia MA, Blanc JJ, Budaj A, Cowie M, Dean V, Deckers J, Burgos EF, Lekakis J, Lindahl B, Mazzotta G, McGregor K, Morais J, Oto A, Smiseth OA, Barbera JA, Gibbs S, Hoeper M, Humbert M, Naeije R, Pepke-Zaba J 2004 Guidelines on diagnosis and treatment of pulmonary arterial hypertension. The Task Force on Diagnosis and Treatment of Pulmonary Arterial Hypertension of the European Society of Cardiology. Eur Heart J 25:2243–2278[Free Full Text]
26. Ojamaa K, Balkman C, Klein IL 1993 Acute effects of triiodothyronine on arterial smooth muscle cells. Ann Thorac Surg 56:S61–S66; discussion S66–S67
27. Danzi S, Klein I 2003 Thyroid hormone and blood pressure regulation. Curr Hypertens Rep 5:513–520[Medline]
28. Smit JW, Eustatia-Rutten CF, Corssmit EP, Pereira AM, Frolich M, Bleeker GB, Holman ER, van der Wall EE, Romijn JA, Bax JJ 2005 Reversible diastolic dysfunction after long-term exogenous subclinical hyperthyroidism: a randomized, placebo-controlled study. J Clin Endocrinol Metab 90:6041–6047[Abstract/Free Full Text]

This article has been cited by other articles:

				S. Ocak, F. Feoli, J. Fastrez, D. Butenda, C. Litvine, I. M. Colin, and J-P d'Odemont Pulmonary arterial hypertension in a patient with stage II sarcoidosis and Hashitoxicosis Eur. Respir. Rev., June 1, 2009; 18(112): 125 - 128. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Siu, C.-W. Articles by Tse, H.-F. Search for Related Content PubMed PubMed Citation Articles by Siu, C.-W. Articles by Tse, H.-F. Related Collections Thyroid Cardiovascular Endocrinology