Autonomic Findings in Takotsubo Cardiomyopathy

Published:November 05, 2015DOI:
      Takotsubo cardiomyopathy (TC) often occurs after emotional or physical stress. Norepinephrine levels are unusually high in the acute phase, suggesting a hyperadrenergic mechanism. Comparatively little is known about parasympathetic function in patients with TC. We sought to characterize autonomic function at rest and in response to physical and emotional stimuli in 10 women with a confirmed history of TC and 10 age-matched healthy women. Sympathetic and parasympathetic activity was assessed at rest and during baroreflex stimulation (Valsalva maneuver and tilt testing), cognitive stimulation (Stroop test), and emotional stimulation (event recall, patients). Ambulatory blood pressure monitoring and measurement of brachial artery flow–mediated vasodilation were also performed. TC women (tested an average of 37 months after the event) had excessive pressor responses to cognitive stress (Stroop test: p <0.001 vs baseline and p = 0.03 vs controls) and emotional arousal (recall of TC event: p = 0.03 vs baseline). Pressor responses to hemodynamic stimuli were also amplified (Valsalva overshoot: p <0.05) and prolonged (duration: p <0.01) in the TC women compared with controls. Plasma catecholamine levels did not differ between TC women and controls. Indexes of parasympathetic (vagal) modulation of heart rate induced by respiration and cardiovagal baroreflex gain were significantly decreased in the TC women versus controls. In conclusion, even long after the initial episode, women with previous episode of TC have excessive sympathetic responsiveness and reduced parasympathetic modulation of heart rate. Impaired baroreflex control may therefore play a role in TC.
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        • Akashi Y.J.
        • Nef H.M.
        • Lyon A.R.
        Epidemiology and pathophysiology of takotsubo syndrome.
        Nat Rev Cardiol. 2015; 12: 387-397
        • Reynolds H.R.
        • Srichai M.B.
        • Iqbal S.N.
        • Slater J.N.
        • Mancini G.B.
        • Feit F.
        • Pena-Sing I.
        • Axel L.
        • Attubato M.J.
        • Yatskar L.
        • Kalhorn R.T.
        • Wood D.A.
        • Lobach I.V.
        • Hochman J.S.
        Mechanisms of myocardial infarction in women without angiographically obstructive coronary artery disease.
        Circulation. 2011; 124: 1414-1425
        • Wittstein I.S.
        • Thiemann D.R.
        • Lima J.A.
        • Baughman K.L.
        • Schulman S.P.
        • Gerstenblith G.
        • Wu K.C.
        • Rade J.J.
        • Bivalacqua T.J.
        • Champion H.C.
        Neurohumoral features of myocardial stunning due to sudden emotional stress.
        N Engl J Med. 2005; 352: 539-548
        • Lanza G.A.
        • Pedrotti P.
        • Pasceri V.
        • Lucente M.
        • Crea F.
        • Maseri A.
        Autonomic changes associated with spontaneous coronary spasm in patients with variant angina.
        J Am Coll Cardiol. 1996; 28: 1249-1256
        • Rosano G.M.
        • Ponikowski P.
        • Adamopoulos S.
        • Collins P.
        • Poole-Wilson P.A.
        • Coats A.J.
        • Kaski J.C.
        Abnormal autonomic control of the cardiovascular system in syndrome X.
        Am J Cardiol. 1994; 73: 1174-1179
        • Akashi Y.J.
        • Barbaro G.
        • Sakurai T.
        • Nakazawa K.
        • Miyake F.
        Cardiac autonomic imbalance in patients with reversible ventricular dysfunction takotsubo cardiomyopathy.
        QJM. 2007; 100: 335-343
        • Norcliffe-Kaufmann L.
        • Axelrod F.
        • Kaufmann H.
        Afferent baroreflex failure in familial dysautonomia.
        Neurology. 2010; 75: 1904-1911
        • Force T.
        Heart rate variability. Standards of measurement, physiological interpretation, and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology.
        Eur Heart J. 1996; 17: 354-381
        • Tank J.
        • Baevski R.M.
        • Fender A.
        • Baevski A.R.
        • Graves K.F.
        • Ploewka K.
        • Weck M.
        Reference values of indices of spontaneous baroreceptor reflex sensitivity.
        Am J Hypertens. 2000; 13: 268-275
        • Jelani Q.U.
        • Norcliffe-Kaufmann L.
        • Kaufmann H.
        • Katz S.D.
        Vascular endothelial function and blood pressure regulation in afferent autonomic failure.
        Am J Hypertens. 2015; 28: 166-172
        • Collen J.
        • Bimson W.
        • Devine P.
        A variant of takotsubo cardiomyopathy: a rare complication in the electrophysiology lab.
        J Invasive Cardiol. 2008; 20: E310-313
        • Rossi A.P.
        • Bing-You R.G.
        • Thomas L.R.
        Recurrent takotsubo cardiomyopathy associated with pheochromocytoma.
        Endocr Pract. 2009; 15: 560-562
        • Bergman B.R.
        • Reynolds H.R.
        • Skolnick A.H.
        • Castillo D.
        A case of apical ballooning cardiomyopathy associated with duloxetine.
        Ann Intern Med. 2008; 149: 218-219
        • Ramanath V.S.
        • Andrus B.W.
        • Szot C.R.
        • Kaplan A.V.
        • Robb J.F.
        Takotsubo cardiomyopathy after midodrine therapy.
        Tex Heart Inst J. 2012; 39: 158-159
        • Lyon A.R.
        • Rees P.S.
        • Prasad S.
        • Poole-Wilson P.A.
        • Harding S.E.
        Stress (takotsubo) cardiomyopathy–a novel pathophysiological hypothesis to explain catecholamine-induced acute myocardial stunning.
        Nat Clin Pract Cardiovasc Med. 2008; 5: 22-29
        • Nef H.M.
        • Mollmann H.
        • Kostin S.
        • Troidl C.
        • Voss S.
        • Weber M.
        • Dill T.
        • Rolf A.
        • Brandt R.
        • Hamm C.W.
        • Elsasser A.
        Tako-tsubo cardiomyopathy: Intraindividual structural analysis in the acute phase and after functional recovery.
        Eur Heart J. 2007; 28: 2456-2464
        • Templin C.
        • Ghadri J.R.
        • Diekmann J.
        • Napp L.C.
        • Bataiosu D.R.
        • Jaguszewski M.
        • Cammann V.L.
        • Sarcon A.
        • Geyer V.
        • Neumann C.A.
        • Seifert B.
        • Hellermann J.
        • Schwyzer M.
        • Eisenhardt K.
        • Jenewein J.
        • Franke J.
        • Katus H.A.
        • Burgdorf C.
        • Schunkert H.
        • Moeller C.
        • Thiele H.
        • Bauersachs J.
        • Tschope C.
        • Schultheiss H.P.
        • Laney C.A.
        • Rajan L.
        • Michels G.
        • Pfister R.
        • Ukena C.
        • Bohm M.
        • Erbel R.
        • Cuneo A.
        • Kuck K.H.
        • Jacobshagen C.
        • Hasenfuss G.
        • Karakas M.
        • Koenig W.
        • Rottbauer W.
        • Said S.M.
        • Braun-Dullaeus R.C.
        • Cuculi F.
        • Banning A.
        • Fischer T.A.
        • Vasankari T.
        • Airaksinen K.E.
        • Fijalkowski M.
        • Rynkiewicz A.
        • Pawlak M.
        • Opolski G.
        • Dworakowski R.
        • MacCarthy P.
        • Kaiser C.
        • Osswald S.
        • Galiuto L.
        • Crea F.
        • Dichtl W.
        • Franz W.M.
        • Empen K.
        • Felix S.B.
        • Delmas C.
        • Lairez O.
        • Erne P.
        • Bax J.J.
        • Ford I.
        • Ruschitzka F.
        • Prasad A.
        • Luscher T.F.
        Clinical features and outcomes of takotsubo (stress) cardiomyopathy.
        N Engl J Med. 2015; 373: 929-938
        • Sharkey S.W.
        • Windenburg D.C.
        • Lesser J.R.
        • Maron M.S.
        • Hauser R.G.
        • Lesser J.N.
        • Haas T.S.
        • Hodges J.S.
        • Maron B.J.
        Natural history and expansive clinical profile of stress (tako-tsubo) cardiomyopathy.
        J Am Coll Cardiol. 2010; 55: 333-341
        • Algra A.
        • Tijssen J.G.
        • Roelandt J.R.
        • Pool J.
        • Lubsen J.
        Heart rate variability from 24-hour electrocardiography and the 2-year risk for sudden death.
        Circulation. 1993; 88: 180-185
        • Tang Y.D.
        • Dewland T.A.
        • Wencker D.
        • Katz S.D.
        Post-exercise heart rate recovery independently predicts mortality risk in patients with chronic heart failure.
        J Card Fail. 2009; 15: 850-855
        • Kleiger R.E.
        • Miller J.P.
        • Bigger Jr., J.T.
        • Moss A.J.
        Decreased heart rate variability and its association with increased mortality after acute myocardial infarction.
        The Am J Cardiol. 1987; 59: 256-262
        • Sandroni P.
        • Benarroch E.E.
        • Low P.A.
        Pharmacological dissection of components of the Valsalva maneuver in adrenergic failure.
        J Appl Physiol. 1991; 71: 1563-1567
        • Derntl M.
        • Woo G.W.
        • Gwechenberger M.
        • Mundigler G.
        • Marx M.
        • Richter B.
        • Gossinger H.D.
        • Gonzalez M.D.
        Tako-tsubo cardiomyopathy complicating left atrial radiofrequency ablation.
        J Cardiovasc Electrophysiol. 2007; 18: 667-671
        • Norcliffe-Kaufmann L.J.
        • Reynolds H.R.
        Afferent baroreflex failure and tako-tsubo cardiomyopathy.
        Clin Auton Res. 2011; 21: 1-2
        • Martin E.A.
        • Prasad A.
        • Rihal C.S.
        • Lerman L.O.
        • Lerman A.
        Endothelial function and vascular response to mental stress are impaired in patients with apical ballooning syndrome.
        J Am Coll Cardiol. 2010; 56: 1840-1846

      Linked Article

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          I read the report by Norcliffe-Kaufmann et al1 published in the January 15, 2015, issue of the Journal, about the autonomic nervous system (ANS) evaluation of 10 women with a history of confirmed Takotsubo syndrome (TTS), which they had suffered more than a mean of 3 years previously, with comparisons with 10 normal control subjects. The authors' ANS comprehensive assessment at rest and during physical, emotional, and cognitive stimulation was further amplified with measurements of brachial artery flow-mediated vasodilation, ambulatory blood pressure monitoring, and plasma catecholamine levels.
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          The work by Norcliffe-Kaufmann et al1 published in a recent issue of the American Journal of Cardiology is commendable. The investigators noted excessive pressor responses to cognitive stress, emotional arousal, and hemodynamic stimuli in patients with takotsubo cardiomyopathy (TC), whereas indexes of parasympathetic modulation of heart rate induced by respiration and cardiovagal baroreflex gain were significantly blunted in TC women compared with controls.1
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        • PDF