CCCardiol CroatCardiologia CroaticaCardiol. Croat.1848-543X1848-5448Croatian Cardiac SocietyCC 2020 15_1-2_16-2110.15836/ccar2020.16Case ReportStress Cardiomyopathy in a Patient with Advanced Stage Amyotrophic Lateral SclerosisStres kardiomiopatija u bolesnice u uznapredovaloj fazi amiotrofične lateralne sklerozehttps://orcid.org/0000-0002-0888-5005Sopek MerkašIvana1*https://orcid.org/0000-0002-2723-8356FučkarKrunoslav12https://orcid.org/0000-0002-9014-9866CerovecDora1https://orcid.org/0000-0002-2329-2582LakušićNenad123https://orcid.org/0000-0003-2432-802XVincelj ŠalkovićLjubica1https://orcid.org/0000-0002-5675-4202CerovecDuško12https://orcid.org/0000-0002-2201-4425ŠestoIgor4Specijalna bolnica za medicinsku rehabilitaciju Krapinske Toplice, Krapinske Toplice, HrvatskaMedicinski fakultet u Osijeku, Sveučilište Josipa Juraja Strossmayera u Osijeku, Osijek, HrvatskaFakultet za dentalnu medicine i zdravstvo Osijek, Sveučilište Josipa Juraja Strossmayera u Osijeku, Osijek, HrvatskaKlinika za kardiovaskularne bolesti Magdalena, Krapinske Toplice, HrvatskaSpecial Hospital for Medical Rehabilitation Krapinske Toplice, Krapinske Toplice, CroatiaFaculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, CroatiaFaculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, CroatiaMagdalena Clinic for Cardiovascular Diseases, Krapinske Toplice, CroatiaADDRESS FOR CORRESPONDENCE: Ivana Sopek Merkaš, Specijalna bolnica za medicinsku rehabilitaciju Gajeva 2, HR-49172 Krapinske Toplice, Croatia. / Phone: + 385 49 383 100 / E-mail: ivana.sopek92@gmail.com012020151-2162105122019201220192020Croatian Cardiac SocietySUMMARY
Stress cardiomyopathy is an entity of unknown etiology characterized by transient systolic dysfunction of the left ventricle and regional wall motion abnormality which suggest myocardial infarction, but with an absence of angiographic evidence of obstructive coronary artery disease. Patients present with chest pain or/and dyspnea, while ECG changes are similar to acute myocardial infarction with ST-elevation. An important factor in the development of stress cardiomyopathy are high catecholamine levels in the blood as a result of the hyperactivity of the sympathetic nervous system caused by a stressful event. Amyotrophic lateral sclerosis (ALS) is an incurable progressive neurodegenerative disease that causes muscle weakness and ultimately ends in death due to respiratory muscle paralysis and respiratory failure. High catecholamine levels and increased sympathetic activity have been described in patients with ALS, which suggests that ALS is a risk factor for developing stress cardiomyopathy. In this article, we present a patient at an advanced stage of ALS who developed stress cardiomyopathy.
SAŽETAK
Stres kardiomiopatija entitet je nepoznate etiologije karakteriziran prolaznom sistoličkom disfunkcijom lijeve klijetke i regionalnim poremećajima kontraktilnosti, koji upućuju na infarkt miokarda, ali bez angiografski značajne opstruktivne koronarne bolesti srca. Klinički, u bolesnika se očituje boli u prsima i/ili dispnejom, a promjene u EKG-u upućuju na akutni infarkt miokarda s elevacijom ST-segmenta. Bitan čimbenik razvoja stres kardiomiopatije povišene su razine katekolamina u plazmi kao rezultat hiperaktivnosti simpatikusa izazvane stresnim događajem. Amiotrofična lateralna skleroza (ALS) progresivna je neurodegenerativna bolest koja zahvaća gornji i donji motoneuron, a najčešće završava smrću zbog paralize mišića za disanje i respiratornog zatajenja. U bolesnika s ALS-om opisane su povišene razine katekolamina i aktivnosti simpatikusa, što čini rizik za razvoj stres kardiomiopatije. U radu je prikazana bolesnica u uznapredovaloj fazi ALS-a s razvojem stres kardiomiopatije.
Stress cardiomyopathy (Takotsubo cardiomyopathy) is characterized by transient systolic dysfunction of the left ventricle and regional wall motion abnormality which suggest myocardial infarction (MI), but with an absence of angiographic evidence of obstructive coronary artery disease (CAD) (1). It is diagnosed in approximately 1-2% of all cases in which MI is suspected (1). Patients present with chest pain or/and dyspnea, while ECG changes are similar to acute myocardial infarction with ST-elevation (STEMI) and laboratory markers in the myocardial lesion are usually mildly to moderately elevated (2-5). ECG typically shows akinesis and apical ballooning of the left ventricle (LV) with reduced systolic function (6). There are also atypical variants, of which the most common are hypokinesis of the middle part of the LV with apical sparing and the variant with akinesis of the basal LV segments and apical hyperkinesis, which is called “reverse” Takotsubo cardiomyopathy (6). The syndrome is significantly more common in menopausal women, and is usually preceded by an episode of emotional, mental, or physical stress (7). There is a higher prevalence of neurological and psychiatric disorders among patients with cardiomyopathy (7). The etiology and pathophysiology of stress cardiomyopathy have not yet been sufficiently elucidated (vasospasm, microvascular disease, etc.) (8), but elevated levels of catecholamines as a result of the hyperactivity of the sympathetic nervous system caused by a stressful event have been described as a cause (9). The activation of specific parts of the brain (hippocampus, brain stem, and basal ganglia) has been demonstrated by measuring increased blood flow in the brain as well as reduced flow to the prefrontal cortex using single photon emission computed tomography (SPECT) in patients with Takosubo cardiomyopathy (10).
Amyotrophic lateral sclerosis (ALS) is an incurable progressive neurodegenerative disease that causes muscle weakness and ultimately ends in death due to respiratory muscle paralysis and respiratory failure (11). It affects the upper and lower motoneurons, and the clinical picture is usually a combination of upper and lower motoneuron dysfunction (12). It can manifest as asymmetric weakness and muscle atrophy in the exterminates that are volitionally innervated (the weakness usually starts in the muscles of the hands) or with manifestation of bulbar symptoms, and later with the development of muscle weakness or exclusively symptoms that include the lower motoneuron (muscle weakness, muscle atrophy, fasciculations). Approximately 50% of patients have symptoms of frontotemporal dementia11. ALS manifests sporadically in 90% of cases and is a familial disease in 10% (11). The familial form of the disease is usually autosomal dominant, but there are also autosomal recessive and X-associated disease types (12). A gene mutation has been found on chromosome 21 that codes the Cu/Zn superoxide dismutase 1 enzyme (SOD1) (13). The pathogenic factors of ALS have not been fully elucidated, and in addition to gene mutation the evidence also indicates autoimmune mechanisms and environmental factors (heavy metals, trauma, radiation, viral infections, smoking, etc.) as possible factors that contribute to the pathogenesis of ALS (12). The disease is more prevalent in men than in women, although at older ages the disease prevalence starts becoming increasingly similar between the sexes. The disease usually manifests between 58 and 63 years of age in the sporadic form and between 47 and 52 years of age in the familial form (11).
Herein we report the case of a 63-year-old patient with ALS at an advanced phase who developed stress cardiomyopathy.
Case report
A 63-year-old female patient with a medical history of ALS that was diagnosed fifteen years ago and with chronic global respiratory insufficiency with the application of continuous home oxygen therapy and consequent paraplegia, multiple spinal discus hernias in the neck area and dyslipidemia, was admitted to the emergency room with a clinical picture of acute coronary syndrome with chest pain starting approximately an hour before arrival and ST-elevation in the V2-V5 to 0.2 mV leads (Figure 1). Based on the clinical picture and ECG, a tentative diagnosis of STEMI with anterolateral localization was established and the patient was referred to urgent coronarography. Coronarography excluded significant obstructive CAD (Figure 2) and treatment was continued at the Intensive Care Unit. Echocardiography showed hypokinesis and discreet ballooning of the septoapical segment of the LV with a borderline global systolic function of 50%. Serial monitoring of myocardial necrosis markers did not find dynamics typical of ACS (peak high-sensitivity troponin concentrations were only 53.3 ng/L). After approximately 3 hours since the onset of the first symptoms, the patient no longer had any chest pain. On the second day of hospitalization the patient developed a clinical picture of refractory global respiratory insufficiency (O2 saturation at 76%; pH 7.09) with consequent hypercapnia (pCO2 15.3 kPa), due to which the patient was intubated and placed on mechanical ventilation. In further course of treatment, the patient was completely dependent on assisted ventilation and could not be removed from the respirator. ECG showed incomplete resolution of the ST-segment elevation on the front wall with the appearance of biphasic T waves in the V2-V5 leads (Figure 3). Echocardiographic control examinations showed complete recovery of kinetics with LVEF recovery to 60%. There were no subsequent signs of heart failure or significant heart rhythm disorders, and the patient was treated symptomatically. The treatment course was prolonged and complicated by the development of respiratory (Pseudomonas aeruginosa) and urinary infections (E. coli, K. pneumoniae ESBL), for which reserve group antibiotics were administered. Given the respiratory status of the patient and since mechanical ventilation would be the destination therapy, the patient received a tracheotomy and was equipped with a home respirator. Due to further chronic care and conditioning requirements of the patient and education of the family, the patient was transferred to a specialized pulmonary center.
ECG in emergency room (elevation of ST-segment up to 0.2 mV which suggests acute ST-segment elevation myocardial infarction of the anterior wall).
(A) Coronary angiogram of the patient – left main coronary artery / left anterior descending artery / circumflex artery. (B) Coronary angiogram of the patient – right coronary artery.
Patient ECG on day 3 of medical treatment (incomplete resolution of ST elevation with biphasic T waves).
Discussion
The patient with advanced ALS we have described developed stress cardiomyopathy followed by rapid development of respiratory insufficiency requiring permanent mechanical ventilation. Considering the clinical course and the available test results as well as our previous clinical experience (14), we established the diagnosis of stress cardiomyopathy despite considering the differential diagnosis of prolonged coronary artery spasm or spontaneous resolution of an intracoronary clot during the first hours of the treatment.
Catecholamine cardiotoxicity associated with sympathetic nervous system hyperactivity has been emphasized as one of the more important pathogenic mechanisms for the development of Takotsubo cardiomyopathy (15). Increased levels of catecholamines have been demonstrated in patients with ALS (16). Autonomic dysfunction in ALS is still not sufficiently elucidated, but there is evidence of reduced activity of the parasympathetic and increased activity of the sympathetic nervous system (17, 18). Sympathetic hyperactivity and elevated concentrations of plasma noradrenaline have been found already in the early stage of ALS (19), although sympathetic hyperactivity is not considered to necessarily be primary in ALS but rather secondary and dependent on the disease progression (20). Takotsubo cardiomyopathy manifests in different neurological diseases (21, 22). The literature describes 20 cases of Takotsubo cardiomyopathy in patients with ALS, and its clinical significance, pathophysiology, and outcomes have not been sufficiently investigated (23-31). Due to the previously described changes in the autonomic nervous system in which the local release of noradrenaline as a consequence of increased sympathetic activity plays a crucial role, ALS represents a risk for the development of Takotsubo cardiomyopathy, which can manifest in the presence of a stress-inducing factor (e.g. infection, respiratory insufficiency, surgical procedure, etc.) (31, 32). This implies the existence of etiological differences between Takotsubo cardiomyopathy in ALS and those in acute neurological disorders where the disease itself causes cardiomyopathy (31). The incidence of Takotsubo cardiomyopathy is higher in ALS in comparison with other forms in the heterogenous group of motor neuron diseases (32) and in comparison with synucleinopathies (Parkinson’s disease, Lewy body dementia, multiple system atrophy), which can also be ascribed to increased sympathetic activity (31). Outcomes in such patients are generally poorer in comparison with those who do not have motor neuron disease, most likely due to weakness of primary musculature as a consequence of the primary illness (32). Latest studies suggested that Takotsubo cardiomyopathy should be suspected in patients with diagnosed ALS who present with chest pain and dyspnea, especially in the advanced phase of the disease (30).
Conclusion
Our patient with advanced ALS was diagnosed with Takotsubo cardiomyopathy on the basis of the clinical picture and patient processing. This avoided prescription of the copious amounts of medication that guidelines recommend for acute MI. Takotsubo cardiomyopathy should be suspected in patients with motor neuron disease and the clinical picture of acute MI, thus avoiding the application of long-lasting and unnecessary medication treatment for non-existent CAD.
LITERATUREAkashiYJGoldsteinDSBarbaroGUeyamaT. Takotsubo cardiomyopathy: a new form of acute, reversible heart failure. . 2008 Dec 16;118(25):2754–62. 10.1161/CIRCULATIONAHA.108.76701219106400Slivnjak V, Lakusic N, Cerovec D, Richter D. [Tako-Tsubo cardiomyopathy; reversible left ventricular dysfunction mimicking acute myocardial infarction with ST-elevation]. Lijec Vjesn. 2009 Jan-Feb;131(1-2):14-7. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/19348350Durasevic Z, Biocic S, Ostricki B, Crnogorac M, Henezi I, Vuksanovic I. Tako-Tsubo – stress induced cardiomyopathy: a case report. Cardiol Croat. 2012;7(1 Suppl):11. Available from: https://www.kardio.hr/2012/10/11/cardiologia-croatica-2012-suppl-1/ (December 2, 2019).Petrović JurenIPršaSČleković-KovačićASoukup PodravecVMilevoj KrižićKIvanac JankovićRTakotsubo cardiomyopathy in a female patient with acute ureterolithiasis. . 2019;14(3-4):74–5. 10.15836/ccar2019.74RadićKVrbanićMŠvađumovićLj. Stress cardiomyopathy: diagnosis and treatment. . 2018;13(11-12):495. 10.15836/ccar2018.495HurstRTParasadAAskewJW3rdSenguptaPPTajikAJ. Takotsubo cardiomyopathy: a unique cardiomyopathy with variable ventricular morphology. . 2010 Jun;3(6):641–9. 10.1016/j.jcmg.2010.01.00920541719TemplinCGhadriJRDiekmannJNappLCBataiosuDRJaguszewskiMClinical features and outcomes of Takotsubo (stress) cardiomyopathy. . 2015 Sep 3;373(10):929–38. 10.1056/NEJMoa140676126332547NefHMMollmannHElsasserA. Tako-tsubo cardiomyopathy (apical ballooning). . 2007 Oct;93(10):1309–15. 10.1136/hrt.2006.10167517890711LyonARReesPSPrasadSPoole-WilsonPAHardingSE. Stress (Takotsubo) cardiomyopathy – a novel pathophysiological hypothesis to explain catecholamine – induced acute myocardial stunning. . 2008 Jan;5(1):22–9. 10.1038/ncpcardio106618094670SuzukiHMatsumotoYKanetaTSugimuraKTakahashiJFukumotoYEvidence for brain activation in patients with takotsubo cardiomyopathy. . 2014;78(1):256–8. 10.1253/circj.CJ-13-127624284957Ralli M, Lambiase A, Artico M, de Vincentiis M, Greco A. Amyotrophic lateral sclerosis: autoimmune pathogenic mechanisms, clinical features and therapeutic perspectives. Isr Med Assoc J. 2019 Jul;21(7):438-43. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31507117Bučuk M, Sijan K, Tomić Z, Sonnenschein I. Amyotrophic lateral sclerosis. Medicina Fluminensis. 2014;50(1):7-20. Available from: https://hrcak.srce.hr/file/175138 (December 2, 2019).RosenDRSiddiqueTPattersonDFiglewiczDASappPHentatiAMutations in Cu/ZN superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. . 1993 Mar 4;362(6415):59–62. 10.1038/362059a08446170SlivnjakVLakusicNRichterDCerovecD. Stress cardiomyopathy with ST-segment elevation of the anterolateral location complicated by a secondary massive intracranial bleeding. . 2009 Aug 21;136(3):e63–5. 10.1016/j.ijcard.2008.05.01318707779Norcliffe-KaufmannLKaufmannHMartinezJKatzSDTullyLReynoldsHR. Autonomic findings in Takotsubo cardiomyopathy. . 2016 Jan 15;117(2):206–13. 10.1016/j.amjcard.2015.10.02826743349ZieglerMGBrooksBRLakeCRWoodJHEnnaSJ. Norepinephrine and gamma aminobutyric acid in amyotrophic lateral sclerosis. . 1980 Jan;30(1):98–101. 10.1212/WNL.30.1.987188643OeyPLVosPEWienekeGHWokkeJHBlankestijnPJKaremakerJM. Subtle involvement of the sympathetic nervous system in amyotrophic lateral sclerosis. . 2002 Mar;25(3):402–8. 10.1002/mus.1004911870718PavlovicSStevicZMilovanovicBMilicicBRakocevic-StojanovicVLavrnicDImpairment of cardiac autonomic control in patients with amyotrophic lateral sclerosis. . 2010 May 3;11(3):272–6. 10.3109/1748296090339085520001491BaltadzhievaRGurevichTKorczynAD. Autonomic impairment in amyotrophic lateral sclerosis. . 2005 Oct;18(5):487–93. 10.1097/01.wco.0000183114.76056.0e16155429YamashitaAKoikeYTakahashiAHirayamaMMurakamiNSobueG. Relationship between respiratory failure and plasma noradrenaline levels in amyotrophic lateral sclerosis. . 1997 Aug;7(4):173–7. 10.1007/BF022679789292242FinstererJWahbiK. CNS disease triggering Takotsubo stress cardiomyopathy. . 2014 Dec 15;177(2):322–9. 10.1016/j.ijcard.2014.08.10125213573PortoIDella BonaRLeoAProiettiRPieroniMCaltagironeCStress cardiomyopathy (tako-tsubo) triggered by nervous system diseases: A systematic review of the reported cases. . 2013 Sep 10;167(6):2441–8. 10.1016/j.ijcard.2013.01.03123415170MatsuyamaYSasagasakoNKoikeAMatsuuraMKogaTKawajiriMAn autopsy case of amyotrophic lateral sclerosis with ampulla cardiomyopathy. . 2008 Apr;48(4):249–54. 10.5692/clinicalneurol.48.24918453156Mitani M, Funakawa I, Jinnai K. [Transient left ventricular apical ballooning, “Takotsubo” cardiomyopathy, in an amyotrophic lateral sclerosis patient on long-term respiratory support]. Rinsho Shinkeigaku. 2005 Oct;45(10):740-3. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/16318369Takayama N, Iwase Y, Ohtsu S, Sakio H. [“Takotsubo” cardiomyopathy developed in the postoperative period in a patient with amyotrophic lateral sclerosis]. Masui. 2004 Apr;53(4):403-6. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/15160667MassariFMTonellaTTarsiaPKiraniSBlasiFMagriniF. Tako-tsubo syndrome in a young man with amyotrophic lateral sclerosis. A case report. . 2011 May;12(5):388–91. 10.1714/643.750621593960SuzukiYOishiMKannoAOgawaKFujisawaMKameiS. Amyotrophic lateral sclerosis accompanying elevated catecholamines occurring as a complication of takotsubo cardiomyopathy. . 2013 Jan;13(1):240–1. 10.1111/j.1447-0594.2012.00943.x23286571PetersS. Tako tsubo cardiomyopathy in respiratory stress syndrome in amyotrophic lateral sclerosis. . 2014 Nov 15;177(1):187. 10.1016/j.ijcard.2014.09.13525499374SantoroFIevaRFerrarettiACarapelleEDe GennaroLSpecchioLMEarly recurrence of Tako-Tsubo cardiomyopathy in an elderly woman with amyotrophic lateral sclerosis: different triggers inducing different apical balloonig patterns. . 2016 Dec;17(2) Suppl 2:e266–8. 10.2459/JCM.0b013e328364dcbc28079765ChoiSJHongYHShinJYYoonBNSohnSYParkCSTakotsubo cardiomyopathy in amyotrophic lateral sclerosis. . 2017 Apr 15;375:289–93. 10.1016/j.jns.2017.02.01228320151IzumiYMiyamotoRFujitaKYamamotoYYamadaHMatsubaraTDistinct incidence of Takotsubo syndrome between amyotrophic lateral sclerosis and synucleinopathies: a cohort study. . 2018 Dec 13;9:1099. 10.3389/fneur.2018.0109930619056FinstererJStollbergerC. Motor neuron disease triggering takotsubo syndrome. . 2016 Nov 15;223:21–2. 10.1016/j.ijcard.2016.08.18527525372