Thiamine-responsive pulmonary hypertension

Abstract

The aim of this report is to call attention to a poorly recognised cause of pulmonary hypertension, thiamine deficiency. A 78-year-old woman without alcoholism or malabsorption presented with progressive dyspnoea and generalised oedema. Echocardiography showed signs of right ventricular overload with an estimated systolic pulmonary artery pressure of 50 mm Hg. Increased lactate concentrations prompted us to investigate thiamine deficiency. A 3-month history of picky eating, relying exclusively on white rice as the staple food, and low blood concentrations of thiamine confirmed the diagnosis. She recovered fully after 12 days of intravenous thiamine administration. Thiamine deficiency should be considered in all patients with pulmonary hypertension of unknown origin.

Background

Pulmonary hypertension occurs in an idiopathic form or in association with underlying diseases or conditions.¹ Although the availability of non-invasive measurement of pulmonary artery systolic pressure with echocardiography has made the diagnosis of pulmonary hypertension easier than before,¹ thiamine deficiency,² of which early recognition and accurate diagnosis is imperative, is not assumed to be a cause of pulmonary hypertension. The present case highlights reversible pulmonary hypertension, a potentially common manifestation of thiamine deficiency.

Case presentation

A 78-year-old woman presented with a 1-month history of progressive dyspnoea and generalised oedema. There was no history of any prior lung disease, such as chronic obstructive pulmonary disease, interstitial lung disease, rheumatological conditions causing interstitial lung disease/pulmonary hypertension, diarrhoea or weight loss indicating malabsorption. She denied smoking, alcoholism, illicit drug use and exposure to lung toxins such as amiodarone or nitrofurantoin. She was in some distress, but was awake. She could tell her history without confabulation. Physical examination showed jugular venous distension, a cardiac third heart sound, bilateral lung coarse crackles and bilateral leg oedema. Her arms, hands and feet showed no signs of rheumatoid arthritis. There was no clubbing. Eye movements were full, without nystagmus. Tendon reflexes and sensation were preserved. Her other physical and neurological findings were also negative. Her blood pressure was 101/60 mm Hg, body temperature was 37°C and pulse was 93 beats/min. Her respiration rate was 36 breaths/r min with oxygen saturation of 94% while breathing 6 l/min of oxygen via a reservoir mask.

Investigations

An ECG showed a normal sinus rhythm with a negative T wave in leads V_3–5 and decreased voltage in the limb leads. Chest x-ray showed congested lungs, moderate cardiomegaly and left pleural effusion (figure 1A,B). Echocardiography showed marked right ventricular dilation and flattening of the interventricular septum with a D-shaped deformation of the left ventricle in later systole and throughout diastole, which indicated right ventricular overload (figure 2). Severe tricuspid regurgitation was found without mitral stenosis or regurgitation. The estimated systolic pulmonary artery pressure as determined on continuous wave Doppler echocardiography was 50 mm Hg. The left ventricular ejection fraction was 67%. Arterial blood gas levels showed lactic acidosis on admission (table 1), when the haemodynamic state was stable. The free T4 and thyroid-stimulating hormone levels were 1.45 ng/dl (reference range, 0.7–1.8 ng/dl) and 2.37 μIU/ml (reference range, 0.3–4.5 μIU/ml), respectively. A chest CT scan with contrast enhancement showed a slightly enlarged trunk of the pulmonary artery but was negative for pulmonary embolism.

Figure 1.

ECG (A) and chest x-ray (B) on admission. The electrocardiogram shows a normal sinus rhythm with negative T waves in leads V_3–5 and decreased voltage in the limb lead. Chest x-ray shows a congestive lung, cardiomegaly and left pleural effusion.

Figure 2.

Parasternal long-axis (left) and short-axis (right) views of 2-dimensional echocardiography showing right ventricular dilation and flattening of the interventricular septum with a D-shaped deformation of the left ventricle in later systole and throughout diastole. LA, left atrium, LV: left, ventricle, RV,: right ventricle.

Table 1.

Arterial blood gas measurements on admission while the patient was breathing oxygen at a flow rate of 6 l/min via a reservoir mask

Variable		Reference range
pH	7.484	7.35–7.45
PaCO2 (mm Hg)	18.4	35–45
PaO2 (mm Hg)	90.3	80–100
Bicarbonate (mmol/l)	13.5	20–26
Lactate (mg/dl)	80	3.3–14.9

Pulmonary hypertension and lactic acidosis prompted us to suspect a beriberi heart and to obtain a history from her daughter about the patient's diet, which was found to have consisted almost exclusively of white rice. The thiamine concentration in the blood, which was sampled and stored on day 2, was subsequently measured and found to be 10 ng/ml (reference range, 20–50 ng/ml).

Treatment

Intravenous thiamine (100 mg/day) was started on day 3.

Outcome and follow-up

On day 4, dyspnoea, bilateral pitting oedema, pleural effusion and cardiomegaly on chest x-rays were markedly reduced. On day 13, she started oral intake, and intravenous thiamine was discontinued. Cardiac catheterisation performed on day 14 showed normal cardiac function with no evidence of a cardiac shunt. The coronary arteries were negative for any stenosis. On day 20, she had no symptoms or signs of heart failure and was transferred to a nursing home.

Discussion

To the best of our knowledge, only seven cases of thiamine-responsive pulmonary hypertension have been reported, including six from East Asia and one from Brazil.^3–8 In the West, where potential causes of thiamine deficiency such as malabsorption, alcoholism and low socioeconomic status are not uncommon, cases of thiamine-responsive pulmonary hypertension can be underdiagnosed simply because most physicians are unaware of the diagnosis.

All previously reported cases involved men with a mean age of 38.5 years (range, 25–57 years). The mean period from the first symptom to admission was 45.8 days (range, 2–150 days). In six cases, hyperdynamic left ventricular function was a key feature raising the suspicion of beriberi heart. In the other case,⁵ the history of beriberi made the diagnosis easier.

In contrast to these previous reports, the present case presented a diagnostic challenge. First, the patient was a woman and much older than any other patient previously reported. Second, the cardiac output was not hyperdynamic. Despite the general belief that the output is high in beriberi heart, the cardiac output and ventricular filling pressure are extremely variable.² The work of both ventricles is increased in thiamine deficiency, but that of the right rises more than that of the left.² Although there is no firm evidence for the best dosage, we could have administered a much higher dose of thiamine.⁹

In summary, the present report revealed that thiamine deficiency can present with pulmonary hypertension. Because thiamine deficiency is not exclusive to Asia or developing countries, there are likely to be more cases of reversible pulmonary hypertension due to thiamine deficiency in developed countries and in the West. Because thiamine deficiency is potentially fatal and readily treatable, empirical treatment with thiamine in cases of pulmonary hypertension of unknown cause merits consideration.

Learning points.

• There are likely to be more cases of reversible pulmonary hypertension due to thiamine deficiency.

• The cardiac manifestation of thiamine deficiency is not necessarily high-output failure.

• Empirical treatment with thiamine in cases of pulmonary hypertension of unknown origin merits consideration.