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

Abstract

BackgroundNemaline 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 presentationWe 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.ConclusionsHF 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.

Sporadic late-onset nemaline myopathy with monoclonal gammopathy of undetermined significance

“…The same study also reported that there was no difference in the survival of the participants aged over 65 years compared to younger participants (eligible patients up to age 80 years were treated in the study) [50], although a prior study of another group had suggested that patients 65 years of age or older should not be considered for the treatment [51]. In SLONM-MGUS, as described early, cardiac muscle involvement is possible, and elderly patients can also be encountered [8,19,20,22]. In such cases, indication of HDM-SCT should be considered more carefully.…”

“…The left ventricular ejection fraction (LVEF) was reduced to 30%, but it recovered to 60% after chemotherapy of bortezomib, cyclophosphamide and dexamethasone, together with selective beta-blockers. In another report, a 37-year-old patient was pointed out to have left ventricular systolic dysfunction due to diffuse hypokinesia within 2 years after the onset of muscle weakness [20]. Subsequently, severe congestive heart failure with 20% of LVEF appeared, and three cardiac arrests due to ventricular tachycardia and fibrillation occurred, requiring intensive care and an implantable cardioverter defibrillator.…”

“…A recent series of case reports have suggested a possibility of cardiac muscle involvement in SLONM-MGUS [19,20,22]. In the report of Belhomme, et al, one SLONM-MGUS patient was admitted to the intensive care unit due to acute heart failure after 2 years from the onset of muscle weakness at the age of 55 years [22].…”

“…Through our literature search in PubMed until April 2017, we identified 31 SLONM-MGUS patients in 19 articles [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. On review of the cases, the disease usually appears in their late 30s or older (the median of onset age is 47 years old [range: 27 -78]).…”

“…SLONM with HIV infection and that with neither MGUS or HIV appear to be heterogeneous, although SLONM with HIV infection is usually responsive to corticosteroid, intravenous immunoglobulin (IVIg), and plasmapheresis [24,25,27,30]. On the other hand, SLONM with MGUS (SLONM-MGUS) patients show a particular phenotype: severe weakness and atrophy in axial, limb-girdle, and occasionally distal muscles, dysphagia, and respiratory insufficiency, which are often refractory to immunotherapy [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. Of note, respiratory involvement is lethal, and the majority of the patients died within 1 to 5 years from the onset [8].…”