Nemaline myopathy and heart failure: role of ivabradine; a case report

BMC Cardiovascular Disorders

Gaetano A Lanza¹  Giorgio Mandalಠ Stefania Marazia³  Emanuela Petrona Baviera⁴  Laura Vassallo⁴  Ylenia Salerno²  Silvia Sarullo⁴  Antonino Di Franco¹  Giuseppe Vitale²  Filippo M Sarullo² 

[1] Department of Cardiology, Catholic University of Sacred Heart, Rome, Italy;Cardiovascular Rehabilitation Unit – Buccheri la Ferla Fatebenefratelli Hospital, Via Salvatore Puglisi n. 15, Palermo, Italy;Department of Cardiology, M. Giannuzzi Hospital, Manduria, Taranto, Italy;University of Palermo, Faculty of Medicine, Palermo, Italy

关键词: Ivabradine;    Dilated cardiomyopathy;    Heart failure;    Nemaline myopathy;   

Others  :  1114630
DOI  :  10.1186/1471-2261-15-5

 received in 2014-09-29, accepted in 2015-01-12,  发布年份 2015

【 摘 要 】

Background

Nemaline myopathy (NM) is a rare congenital myopathy characterized by muscle weakness, hypotonia and the presence in muscle fibers of inclusions known as nemaline bodies and a wide spectrum of clinical phenotypes, ranging from severe forms with neonatal onset to asymptomatic forms. The adult-onset form is heterogeneous in terms of clinical presentation and disease progression. Cardiac involvement occurs in the minority of cases and little is known about medical management in this subgroup of NM patients. We report a rare case of heart failure (HF) in a patient with adult-onset NM in whom ivabradine proved to be able to dramatically improve the clinical picture.

Case presentation

We report a case of a 37-year-old man with adult-onset NM, presenting with weakness and hypotonia of the proximal limb muscles and shoulder girdle, severely limiting daily activities. He developed progressive HF over a period of 6 months while attending a rehabilitation program, with reduced left ventricular ejection fraction (LVEF = 20%), manifested by dyspnea and signs of systemic congestion. The patient was started HF therapy with enalapril, carvedilol, spironolactone and loop diuretics. Target HF doses of these drugs (including carvedilol) were not reached because of symptomatic hypotension causing a high resting heart rate (HR) ≥70 beats per minute (bpm). Further deterioration of the clinical picture occurred with several life-threatening arrhythmic episodes requiring external defibrillation. An implantable cardioverter defibrillator (ICD) was then implanted. Persistent high resting HR was successfully treated with ivabradine with HR lowering from 90 bpm to 55 bpm at 1 month follow up, LVEF rising to 50% at 3 month follow up and to 54% at 2,5 year follow up. To date no more hospitalizations for heart failure occurred. A single hospitalization due to aspiration pneumonia required insertion of a tracheostomy tube to protect airways from further aspiration. At present, the patient is attending a regular rehabilitation program with net improvement in neuromotor control and less limitations in daily activities.

Conclusions

HF is a rare feature of NM, but it can negatively influence prognosis. Conventional HF therapy and/or heart transplant are the only reasonable strategy in these patients. Ivabradine is a useful, effective and safe drug for therapy in NM patients with HF and should be considered when resting HR remains high despite beta-blockers’ full titration or beta-blockers’ underdosing due to intolerance or side effects.

【 授权许可】

   
2015 Sarullo et al.; licensee BioMed Central.

【 图 表 】

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【 参考文献 】

• [1]North KN, Laing NG, Wallgren-Pettersson C: Nemaline myopathy: current concepts. The ENMC International Consortium on Nemaline Myopathy. J Med Genet 1997, 34:705-713.
• [2]Palmucci L, Doriguzzi C, Mongini T, Chiado-Piat L: Adult onset nemaline myopathy: a distinct nosologic entity? Clin Neuropathol 1993, 12:153-5.
• [3]Chahin N, Selcen D, Engel AG: Sporadic late onset nemaline myopathy. Neurology 2005, 65:1158-64.
• [4]Eymard B, Brouet JC, Collin H, Chevallay M, Bussel A, Fardeau M: Late-onset rod myopathy associated with monoclonal gammopathy. Neuromusc Disord 1993, 3:557-60.
• [5]Keller CE, Hays AP, Rowland LP, Moghadaszadeh B, Beggs AH, Bhagat G: Adult-Onset nemaline myopathy and monoclonal gammopathy. Arch Neurol 2006, 63:132-13.
• [6]Gatayama R, Ueno K, Nakamura H, Yanagi S, Hideaki U, Yamagishi H, Yasui S: Nemaline myopathy with dilated cardiomyopathy in childhood. Pediatrics; 2013, 131:e1-e5.
• [7]Meier C, Gertsch M, Zimmermann A, Voellmy W, Geissbühler J: Nemaline myopathy in adults as a cardiomyopathy. A clinicopathologic study. NEJM 1983, 308(25):1536.
• [8]Stoessl AJ, Hahn AF, Malott D, Jones DT, Silver MD: Nemaline myopathy with associated cardiomyopathy. Report of clinical and detailed autopsy findings. Arch Neurol 1985, 42(11):1084-1086.
• [9]Nagata R, Kamimura D, Suzuki Y, Saito T, Toyama H, Dejima T, et al.: A case of nemaline myopathy with associated dilated cardiomyopathy and respiratory failure. Int Heart J 2011, 52:401-405.
• [10]Lomen-Hoerth C, Simmons ML, Dearmond SJ, Layzer RB: Adult-onset nemaline myopathy: another cause of dropped head. Muscle Nerve 1999, 22(8):1146-1150.
• [11]Engel WK, Oberc MA: Abundant nuclear rods in adult onset rod disease. J Neuropathol Exp Neurol 1975, 34:119-132.
• [12]Gyure KA, Prayson RA, Estes ML: Adult-onset nemaline myopathy: a case report and review of the literature. Arch Pathol Lab Med 1997, 121(11):1210-1213.
• [13]Kannel WB, Kannel C, Paffenbarger RSJR, Cupples LA: Heart rate and cardiovascular mortality: the Framingham Study. Am Heart J 1987, 113(6):1489-94.
• [14]Fox K, Borer JS, Camm AJ, Danchin N, Ferrari R, Lopez Sendon JL, Steg PG, Tardif JC, Tavazzi L, Tendera M: Resting heart rate in cardiovascular disease. J Am Coll Cardiol 2007, 50(9):823-30.
• [15]Kjekshus J, Gullestad L: Heart rate as a therapeutic target in heart failure. Eur Heart J 1999, 1(Suppl H):H64-9.
• [16]Greene SJ, Vaduganathan M, Wilcox JE, Harinstein ME, Maggioni AP, Subacius H, et al.: The prognostic significance of heart rate in patients hospitalized for heart failure with reduced ejection fraction in sinus rhytm. Insights from the EVEREST (Efficacy of Valpression Antagonism in Herat Fialure: Outcome Study With Tolvaptan) Trial. J Am Coll Cardiol HF 2013, 1:488-496.
• [17]Habal MV, Liu PP, Austin PC, Ross HJ, Newton GE, Wang X, et al.: Association of heart rate at hospital discharge with mortality and hospitalizations in patients with heart failure. Circ Heart Fail 2014, 7:12-20.
• [18]CIBIS-II Investigators and Committees: The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet 1999, 353:9-13.
• [19]Willwnheimer R, van Veldhuisen DJ, Silke B, Erdmann E, Follath F, Krum H, CIBIS III Investigators, et al.: Effect on survival and hospitalization of initiating treatment for chronic heart failure with bisoprolol followed by enalapril, as compared with the opposite sequence: results of the randomized cardiac insufficiency bisoprolol study (CIBIS) III. Circulation 2005, 112(16):2426-35.
• [20]Bristow MR, Gilbert EM, Abraham WT, Adams KF, Fowler MB, Hershberger RE, et al.: Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure. MOCHA Investigators. Circulation 1996, 94(11):2807-16.
• [21]Fiuzat M, Wojdyla D, Kitzman D, Fleg J, Keteyian SJ, Kraus WE, et al.: Relationship of beta-blocker dose with outcomes in ambulatory heart failure patients with systolic dysfunction: results from the HF-ACTION (Heart Failure: a Controlled Trial Investigating Outcomes of Exercise Training) trial. J Am Coll Cardiol. 2012, 60:208-15.
• [22]McAlister FA, Wiebe N, Ezekowitz JA, Leung AA, Armstrong PW: Meta-analysis: beta-blocker dose, heart rate reduction, and death in patientss with heart failure. Ann Intern Med 2009, 150(11):784-94.
• [23]Flannery G, Gehrig-Mills R, Billah B, Krum H: Analysis of randomized controlled trials on the effect of magnitude of heart rate reduction on clinical outcomes in patients with systolic chronic heart failure receiving beta-blockers. Am J Cardiol 2008, 101(6):865-9.
• [24]Di Franco A, Sarullo FM, Salerno Y, Figliozzi S, Parrinello R, Di Pasquale P, Lanza GA: Beta-blockers and ivabradine in chronic heart failure: from clinical trials to clinical practice. Am J Cardiovasc Drugs 2014, 14(2):101-110.
• [25]Sarullo FM, Fazio G, Puccio D, Fasullo S, Paterna S, Novo S, Di Pasquale P: Impact of “Off-Label” use of Ivabradine on exercise capacity, gas exchange, functional class, quality of life, and neurohormonal modulation in patients with ischemic chronic heart failure. J Cardiovasc Pharmac Ther 2010, 15:349-355.
• [26]Swedberg K, Komajda M, Böhm M, Borer J, Robertson M, Tavazzi L, Ford I, for the SHIFT Investigators: Effects on outcomes of heart rate reduction by ivabradine in patients with congestive heart failure: is there an influence of beta-blocker dose? J Am Coll Cardiol 2012, 59:1938-1945.
• [27]Taglia A, D’Ambrosio P, Palladino A, Politano L: On a case of respiratory failure due to diaphragmatic paralysis and dilated cardiomyopathy in a patient with nemaline myopathy. Acta Myologica 2012, XXXI:201-203.