Heart Failure and Polycythemia: A Case Report and Literature Review

INTRODUCTION

Heart failure (HF) is the terminal manifestation of various cardiovascular diseases; the management is still challenging when faced with various etiologies and exaggerating factors.

Polycythemia is an abnormal elevation of hemoglobin (Hb) and hematocrit (Hct) in peripheral blood circulation.¹ It can be divided into primary and secondary polycythemia according to the etiology. Primary polycythemia mainly results from the increased erythroid progenitor cells due to an intrinsic cellular defect; whereas secondary polycythemia is a heterogeneous group of elevated red blood cell mass due to tissue hypoxia or physiologically inappropriate secretion of erythropoietin and/or other contributing factors, e.g., obesity, sleep apnea, hypoventilation, chronic obstructive pulmonary diseases, smoking or diuretics use.¹

The estimated prevalence of polycythemia in HF is from 1.2% to 5.9% but could be underestimated due to decreased awareness and unavailable diagnostic tools.² Although diuretics have been suggested to ameliorate HF symptoms, it may worsen the polycythemia due to a concentrated plasma and hyperviscosity. On the other hand, phlebotomy has been considered for the control of Hct in polycythemia, but the treatment of polycythemia in HF patients remains ambiguous. Hence, we describe an HF patient with polycythemia and provide a literature review to discuss the diagnostic algorithm and management of HF and polycythemia.

CASE PRESENTATION

A 41-year-old male with cigarette smoking for over 20 years and a body mass index of 24.3 kg/m² had a history of coronary artery disease post percutaneous coronary intervention with a stent in the left circumflex artery and HF. He came to our emergency department due to progressive dyspnea on exertion and pitting edema over the bilateral lower extremities within one week. His vital signs showed a body temperature of 36 °C, heart rate and respiratory rate of 130 beats and 18 times per minute (bpm), systolic and diastolic blood pressure of 143 and 115 mmHg, and peripheral oxygen saturation (SpO₂) of 92%. Physical examinations revealed rales breath sounds at bilateral chest areas, rapid and irregular heartbeats, engorged jugular vein, and severely edematous bilateral lower extremities. Hb and Hct were 20.5 g/dL (normal: 13.5-17.5 g/dL) and 62.9% (normal: 40%-49%), respectively; white blood cell and platelet counts were within the normal range. The N-terminal pro B type natriuretic peptide (NT-proBNP) yielded 9407.0 pg/mL (normal: < 125 pg/mL). An electrocardiogram presented atrial fibrillation (Afib) with a rapid ventricular response (134 bpm). Chest X-ray films revealed cardiomegaly and bilateral pulmonary edema.

Loop diuretics were given for initial symptomatic relief. However, after short-term relief of symptoms, his Hb rose to 21.2 g/dL. Tachycardia and dyspnea reoccurred, and loop diuretics were held to avoid a concentrated plasma. We performed a phlebotomy with 750 ml blood and infused 500 ml normal saline. His Hb and Hct levels dropped to 18.5 g/dL and 56.2%, and the symptoms improved. His vital signs returned to a heart rate of 68 bpm, respiratory rate of 18 times per minute, blood pressure of 102/58 mmHg and SpO₂ of 98% under room air.

Workup for HF was carried out. Trans-thoracic echocardiogram showed a dilated left atrium, left ventricular remodeling concentric hypertrophy and reduced left ventricular ejection fraction of 36% (Figure 1A). Coronary angiogram showed patent coronary arteries without in-stent stenosis. Cardiac magnetic resonance imaging disclosed a dilated left atrium and concentric left ventricle hypertrophy (Figure 1B). A late gadolinium enhancement pattern associated with myocardial scarring with ill-defined patchy in the mid-wall was found (Figure 1C). Reviewing this patient’s history, we found that the hospitalization for HF was associated with polycythemia (Figure 2A). Notably, HF symptoms were relieved shortly after phlebotomy during the hospitalization for HF.

Figure 1.

(A) The echocardiography showed dilated left atrium and remodeling concentric left ventricular hypertrophy. (B) The cardiac magnetic resonance imaging disclosed dilated left atrium, concentric left ventricle hypertrophy and no abnormal perfusion defect in the resting status. (C) Ill-defined patchy mid-wall late gadolinium enhancement pattern revealed myocardial scarring.

Figure 2.

(A) The diagram shows the trajectory of hemoglobin, hematocrit and N-terminal pro B type natriuretic peptide (NT-proBNP) in hospitalizations for heart failure and the outpatient department. (B) The figure shows the work-up and management for polycythemia and heart failure in the patient. eGFR, estimated glomerular filtration rate; HHF, hospitalizations for heart failure; LVH, left ventricular hypertrophy; LVEF, left ventricular ejection fraction; MRI, magnetic resonance imaging; NT-proBNP, N-terminal pro B type natriuretic peptide; RBC, red blood cell. * Chest X-ray film: cardiomegaly and bilateral pulmonary edema. ^† Electrocardiogram: atrial fibrillation and rapid ventricular response.

Workup for polycythemia was carried out. First, a gene test of Janus kinase-2 (JAK-2) showed negative results. The erythropoietin (Epo) level was 16.8 mIU/mL (normal: 4.4-29.0 mIU/mL). The peripheral blood film showed an increased density of red blood cells, i.e., 6.62 × 10⁶/μL (normal: 4.26-5.56 × 10⁶/μL). Obstructive sleep apnea was not observed during hospitalization. The values of serum creatinine and estimated glomerular filtration rate were 1.17 mg/dL (normal: 0.72-1.25 mg/dL) and 68.7 ml/min/1.73 m². The carboxyhemoglobin was 4.5% (normal value: 1.5%). The serum iron was 43 μg/dL (normal: 50-160 μg/dL) and serum ferritin was 19.7 ng/mL (normal: 21.8-274.7 ng/mL). Abdominal ultrasonography did not show splenomegaly nor renal artery stenosis. The results of the pulmonary function test were normal. The bone marrow smear revealed that the megakaryocytes and erythroid lineages were normal in morphology and quantity, and there was no excess of blasts. Immunohistochemical staining with anti-CD34, anti-CD117, CD71, MPO, CD61 did not show acute leukemia, polycythemia vera nor myeloproliferative neoplasm. Collectively, there was no evidence to support primary polycythemia; and secondary polycythemia was favored due to chronic hypoxemia and volume depletion resulting from smoking and diuretics (Figure 2B).

After two-weeks of management with intermittent diuretics and phlebotomy, HF guideline-directed medical therapy (i.e., renin-angiotensin-aldosterone system inhibitor, beta-blockade and mineralocorticoid receptor antagonist), non-vitamin K antagonist oral anticoagulants (NOACs) for stroke and thromboembolism prevention in Afib, and multidisciplinary-team care including a smoking-cessation program and dietary advice (Figure 2B), he was in remission and was followed up in our cardiovascular outpatient department.

DISCUSSION

Differential diagnosis of polycythemia

Primary polycythemia, including polycythemia vera, is a rare form of chronic myeloproliferative neoplasm diseases, which can lead to elevated hemoglobin levels, hypercoagulability and even cardiac disfunction.¹ Secondary polycythemia can be caused by hypoxia and cardiopulmonary diseases, e.g., chronic pulmonary diseases, right-to-left cardiac shunts, obstructive sleep apnea, obesity hypoventilation syndrome (Pickwickian syndrome), high altitude and chronic carbon monoxide poisoning (including heavy smoking).^1,2

For this patient, primary polycythemia was excluded based on a series of laboratory and blood tests, image examinations, negative JAK-2 and bone marrow findings, and Epo values (Figure 2B). On the contrary, this patient was a heavy smoker who had a high carboxyhemoglobin level. Besides, he had long-term diuretic use after being diagnosed with HF. Hence, secondary polycythemia was favored. Notably, although he did not quit smoking successfully and only reduced the cigarette volume, his Hb and Hct dropped to 17.2 g/dL and 52.4% two months after discontinuing loop diuretics. The findings support our diagnosis of secondary polycythemia.

Polycythemia and heart failure

Once HF patients have polycythemia, prompt and appropriate management is needed. Polycythemia in HF may increase the risk of stroke and myocardial infarction, because high Hb levels can cause systemic thromboembolism and vasoconstriction by trapping nitric oxide and generating oxygen-derived free radicals.³ Lim W.H. et al. presented that when Hb is higher than 16 mg/dL in men and 15 mg/dL in women, the risk of Afib occurrence increases by 22% in men and 29% in women, respectively.⁴ In this patient, we noted that paroxysmal Afib was associated with polycythemia, and the concomitant occurrence of this status worsened HF symptoms.

Management of polycythemia in HF patients

So far, unlike anemia, no consensus in managing polycythemia in HF has been reached. The treatment strategies depend on the etiology involved and should correct the precipitating factors and the hematologic abnormality.² For example, the use of diuretics and androgens should be reviewed and adjusted to appropriate doses or discontinued in HF patients with polycythemia. Iron deficiency should be avoided because this condition may induce the overproduction of microcytic hypochromic red blood cells and then cause a hyperviscosity state. Low-flow oxygen therapy may be considered for hypoxia patients; however, judicious use, close monitoring, and avoidance of oxygen intoxication and respiratory depres-sion are crucial. Additionally, low-dose aspirin may be beneficial for thromboembolism prevention,⁵ and NOACs could be used for venous thromboembolism and stroke prevention in atrial fibrillation.⁶

Traditionally, phlebotomy has been indicated in polycythemia patients with hypoxia conditions, e.g., chronic lung diseases and cyanotic heart disease. Some studies have reported that phlebotomy could improve oxygen consumption, cardiac output and exercise tolerance in patients with polycythemia.⁷ Dayton et al. showed that phlebotomy could benefit the clinical performance of patients with chronic lung diseases, particularly those with HF and an Hct of more than 60%.⁸ Segal and Bishop presented that repeated phlebotomy slightly reduces the various indices in patients with severe lung diseases and congestive HF.⁹ However, the guidelines of the American College of Cardiology/American Heart Association only suggested performing therapeutic phlebotomy in patients who have cyanotic heart disease and high Hb and Hct levels (> 20 g/dL and 65%), and during the procedure, iron depletion and dehydration should be avoided.¹⁰

LEARNING POINTS

Management of acute decompensated HF concomitant with polycythemia is challenging and a potential dilemma due to using diuretics. This case study may help to deal with this complicated condition. First, etiology survey and differential diagnosis for polycythemia are crucial because the treatment depends on the causes. Second, low-flow oxygen may improve hypoxia, while intoxication or respiratory suppression should be avoided for oxygen supplements. Third, aspirin may be beneficial for the prevention of thromboembolism due to the hyperviscosity status, and NOACs could prevent Afib-related stroke and venous thromboembolism. Fourth, although diuretics are suggested in HF management, it should be utilized with caution to avoid volume depletion and hyperviscosity. Last, phlebotomy requires prudent evaluation, and iron depletion should be avoided.

DECLARATION OF CONFLICT OF INTEREST

All the authors declare no conflict of interest.