Effects of selective If-channel inhibition with ivabradine on hemodynamics in a patient with restrictive cardiomyopathy

Heart-rate reduction is a major goal in treatment of patients with coronary artery disease (CAD) and chronic congestive heart failure [1, 2], and an elevated resting pulse robustly correlates with decreased survival in these patients [3]. Therefore, heart rate reduction down to 55–60 bpm is recommended in the current guidelines for the treatment of CAD of the American Heart Association [4] and of the European Society of Cardiology [5] alike. The selective If-channel inhibitor ivabradine represents a novel pharmaceutical to achieve this goal [6]. In an experimental trial in a rodent model of heart failure, ivabradine was demonstrated to increase stroke volume, improve LV-function, and beneficially influence myocardial remodeling [7]. Whether the use of this drug is beneficial in patients with established systolic chronic heart failure, is currently under investigation in the SHIFT trial [8]. The treatment of restrictive cardiomyopathy, e.g., due to cardiac amyloidosis, however, differs substantially from that of patients with systolic heart failure due to ischemic heart disease or idopathic dilated cardiomyopathy. Special attention must be payed to fluid balance, and blood pressure lowering drugs must be administered carefully due to the development of profound hypotension; in addition, the usefulness of betablockers in patients with sinus rhythm has not been tested in cardiac amyloidosis [9]. So far, there are also no data about the effects of ivabradine in patients with cardiac amyloidosis, and data are lacking, if a heart rate reduction per se can improve hemodynamics, outcomes, or quality-of-life in patients with restrictive cardiomyopathy. We here report on a 78-year old male who was admitted to our emergency room with symptoms of decompensated congestive heart failure (pulmonary congestion, massive peripheral edema, pleural effusion), hypotension, and acute on chronic renal failure (creatinine 2.08 mg/dl, urea-N 83 mg/dl). Brain natriuretic peptide levels exceeded 5,000 pg/ml. The initial ECG showed a left axis, sinus rhythm, tachycardia of 110 bpm, and a Sokolow-LyonIndex of 3.5 mV. It is noteworthy that the patient had no history of arterial hypertension. A therapy with furosemide i.v. was initiated to recompensate the patient. This kind of therapy was not successful and the patient could not get rid of the massive peripheral edema, and we could not reduce the body weight. Echocardiography revealed the picture of a restrictive cardiomyopathy (see Fig. 1). Cardiac MRI showed diffuse hyperenhancement typical for amyloidois. Cardiac catheterization revealed a cardiac index (CI) of 1.2 l/min/m, a dip-plateau-phenomenon, and a tachycardia of 90–100 bpm. The coronary arteries were free of significant stenosis. Histological examination of a right-ventricular biopsy revealed a positive Kongo-red-staining proving the diagnosis cardiac amyloidosis, which was secondary to monoclonal gammopathy type lambda. Due to severe hypotension, diuretic resistance to high doses of furosemide and a marked tachycardia at rest was noted. Due to the low blood pressure, treatment with betablockers was not possible. The poor clinical state of the patient did not allow an aggressive treatment of the amyloidosis, e.g., using alkylating agents like melphalan. Slowing down the heart rate in patients with restrictive cardiomyopathy via use of digoxin and betareceptor P. Wenzel (&) N. Abegunewardene T. Munzel Universitatsmedizin der Johannes-Gutenberg-Universitat Mainz, II. Medizinische Klinik—Kardiologie, Angiologie und Internistische Intensivmedizin, Langenbeckstr. 1, 55131 Mainz, Germany e-mail: wenzelp@uni-mainz.de