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Fingolimod in a patient with heart failure on the background of pulmonary arterial hypertension and coronary artery disease
© Thomas et al.; licensee BioMed Central Ltd. 2014
Received: 24 April 2014
Accepted: 3 June 2014
Published: 7 June 2014
Fingolimod is the first oral immunomodulatory therapy approved for highly active relapsing remitting multiple sclerosis. Based on the distribution pattern of fingolimod interacting sphingosine-1-phosphat receptors in organism including immune system and cardiovascular system clinical monitoring of patients and evaluation of adverse events are recommended. Despite extensive data on cardiovascular safety, experience with fingolimod in patients with concomitant cardiological disease, especially within the pulmonary circulation, is rare.
We report the case of a 46-year-old woman presented with relapsing remitting multiple sclerosis and severe idiopathic pulmonary arterial hypertension. Fingolimod was initiated because of disease activity of multiple sclerosis with two relapses and gadolinium-enhancing lesions in MRI. The patient demonstrated stable disease course of idiopathic pulmonary arterial hypertension when fingolimod was started. Fingolimod therapy did not alter or even worsen the pulmonary or cardiovascular conditions during first dose application as well as follow up of nine months.
In this report, we present the first case of fingolimod treatment in a patient with highly active multiple sclerosis and severe idiopathic pulmonary arterial hypertension. We suggest an interdisciplinary approach with detailed cardiopulmonary monitoring for safety in such patients.
Fingolimod is approved as second line disease modifying drug for highly active relapsing remitting multiple sclerosis (MS) patients. In its phosphorylated form it serves as sphingosine-1-phosphat (S1P) receptor analogue, orchestrating relevant mechanisms in the immune system but also cardiovascular system . There are only few reports on S1P-triggered effects on cardiovascular function within systemic or pulmonary circulation.
Right and left ventricular parameter before and after fingolimod application
Post-FTY 1 month
3 month follow up
9 month follow up
Right ventricle hypertrophy
PO2 (cap.) [kPa]
PCO2 (cap.) [kPa]
TLCO SB 49%
TLCO SB 51%
TLCO SB 53%
TLCO SB 50%
TLCO SB 49%
Parameter of systemic circulation during passive orthostatic tilt test before and after fingolimod application
2 h post-FTY
4 h post-FTY
6 h post-FTY
3 month follow-up
9 month follow-up
TPR [mmHg *s/ml]
In this report, we present the first case of fingolimod treatment in a patient with severe IPAH and coronary heart disease. Although there were no short- and long-term side effects by fingolimod in this patient, patients with cardiovascular disease should be carefully selected for fingolimod therapy. It is necessary to evaluate existing cardiovascular conditions inclusive the medication critically. An interdisciplinary approach with frequent cardio-pulmonary exams like ECG, BP, echocardiography, body plethysmography and blood gas analysis should be complemented to monitor and ensure safety in such patients.
Fingolimod is known as S1P receptor analogue that mediates inhibition of lymphocyte egress from lymph nodes into the peripheral blood . Beside the immune system S1P receptors are also relevant for further signallining inside the human body including the cardiovascular and pulmonary system. Based on the natural distribution pattern of S1P receptors especially on artrial myocytes, fingolimod can cause transient bradycardia or decrease of atrioventricular conduction . It is known, that S1P promotes contraction of bronchi and especially bronchial smooth muscle cells [5, 6]. Furthermore increased risk of arterial hypertension and vascular dysfunction caused by S1P receptor subtypes in endothelium and smooth muscle cell layer is discussed during fingolimod treatment [7, 8]. Today, there is extensive experience regarding safety and tolerability during first dose application and long-term treatment with fingolimod in MS patients . Several fingolimod-related cardiovascular side effects have been discussed so far including prolonged symptomatic bradycardia, AV block or non-fatal cardiac asystole at first dose application or ventricular arrhythmia after five months of treatment [10–12]. A critical arterial vasospasm of the left arm seven days after initiation of fingolimod was also presented . In a patient with Wolff-Parkinson-White syndrome, no cardiovascular interaction with fingolimod was described . Nevertheless, data on fingolimod treated patients with definite concomitant cardiac diseases are rare, especially if the right side of the heart is involved.
IPAH is characterized by elevated pulmonary arterial pressure and pulmonary vascular resistance causing right ventricular hypertrophy and insufficiency. Early intervention is necessary to avoid right heart failure and sudden death. In our case, symptoms and objective assessment associated with IPAH improved after treatment initiation. Fingolimod was started during a stabilized disease course of IPAH over two years. Fingolimod therapy did not alter or even worsen the pulmonary or cardiovascular conditions during first dose application as well as during follow up.
Written informed consent was obtained from the patient for publication of this Case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.
KT, HS, MH and TZ diagnosed and treated the patient. KT wrote the draft manuscript, prepared and analysed testings and data. HS and MH were involved drafting the manuscript. TZ initiated the study, reviewed and edited the manuscript and approved the final version. All authors read and approved the final manuscript.
This work was supported by German Research Foundation and Publishing Fund of the University of Technology Dresden.
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