+ MODEL Hellenic Journal of Cardiology (2016) xx, 1e3 Available online at www.sciencedirect.com ScienceDirect journal homepage: http://www.journals.elsevier.com/ hellenic-journal-of-cardiology/ LETTER TO THE EDITOR Paradoxical bradycardia and blood pressure elevation during dobutamine stress echocardiography reveal ischemia in a patient with syncope KEYWORDS stress echocardiography; dobutamine; bradycardia; syncope Non-invasive cardiac imaging for detecting myocardial ischemia has been suggested to assess the need for revascularization in case of coronary atherosclerosis.1 Dobutamine stress echocardiography (DSE) has been widely accepted as a safe method for identifying ischemia-causing coronary artery disease and has a sensitivity of 77% and specificity of 75%.1-3 Another method that detects hemodynamically significant coronary atherosclerosis, at the expense of radiation, is single-photon emission computed tomography using adenosine as a stressor, which has a sensitivity of 70% and specificity of 78%.1 DSE should be performed according to the appropriateness criteria to increase its diagnostic accuracy and prognostic value.4 A clinical scenario with high appropriateness scoring is a symptomatic patient after the early period of revascularization.4 The most common symptom is angina, but syncope without preceding symptoms could be an alternative sign of transient myocardial ischemia A case of a patient with syncope investigated for ischemia is presented; DSE yielded the diagnosis with a response of paradoxical bradycardia and concomitant blood pressure elevation A 55-year-old male presented to the emergency department due to two syncopal episodes while walking Abbreviations: DSE, dobutamine stress echocardiography; LV, left ventricular; RCA, right coronary artery Peer review under responsibility of Hellenic Cardiological Society The patient had known coronary artery disease and underwent percutaneous intervention of the right coronary artery (RCA) years prior On admission, he was on sinus rhythm with negative T waves in leads III and aVF, which were stable findings compared to years ago A highsensitivity cardiac troponin assay was within the normal range He had no angina-like symptoms or troponin elevation Although the D-dimers were elevated, a computed tomography pulmonary angiography excluded the presence of aortic dissection or pulmonary embolism A thorough neurological investigation revealed normal findings The patient was admitted to the Cardiology Department Echocardiography revealed good LV systolic function A 48hour Holter monitor indicated sinus rhythm without significant arrhythmia Carotid sinus massage and the tilt test provided no evidence of a vasovagal etiology of syncope A techitium-99m single-photon emission computed tomography scan with adenosine was performed and ruled out myocardial ischemia The clinical scenario of ischemia leading to syncope was still considered Before discharge, a DSE was performed At rest, the LV systolic function was preserved with no regional wall motion abnormalities The dobutamine infusion started at mg/kg/min and was increased to 10 and 20 mg/kg/min every minutes Until the dose of 20 mg/kg/min, the heart rate became paradoxically lower and the blood pressure was significantly increased; a heart rate of 40 beats per minute was recorded in sinus rhythm and the blood pressure increased up to 225/110 mmHg (Table 1) The infusion rate was increased from 20 to 30 mg/kg/min within minute and the heart rate started increasing Finally, 88% of the target heart rate was achieved At this point, the systolic function was improved and LV volume was reduced, and there were no regional wall motion abnormalities At recovery, hypokinesia of the basal inferior and akinesia of the mid-inferior wall was observed (Videos 1, 2, and 3) DSE was reported positive for ischemia of the inferior wall Subsequently, coronary angiography was performed and an ostial lesion of the RCA, causing 90% stenosis, was visualized and treated with http://dx.doi.org/10.1016/j.hjc.2016.11.025 1109-9666/ª 2016 Hellenic Cardiological Society Publishing services by Elsevier B.V This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) Please cite this article in press as: Kamperidis V, et al., Paradoxical bradycardia and blood pressure elevation during dobutamine stress echocardiography reveal ischemia in a patient with syncope, Hellenic Journal of Cardiology (2016), http://dx.doi.org/10.1016/ j.hjc.2016.11.025 + MODEL Letter to the Editor Table Heart rate and blood pressure response to dobutamine stress echocardiography Stages Dobutamine (iv), mg/kg/min Heart Rate, beats per minute Blood Pressure, mmHg Rest Stress e 10 20 30 40 ỵ Atropine 0.5 mg e 65 56 45 40 71 89 145 90 127/93 133/80 180/90 225/110 190/110 207/97 212/107 126/87 Recovery* * Recovery was recorded minutes after infusion of mg of metoprolol (iv) percutaneous stenting One day later, the patient was safely discharged At 3-month follow-up, he remained asymptomatic Supplementary data related to this article can be found online at http://dx.doi.org/10.1016/j.hjc.2016.11.025 The present case suggests that when DSE produces a paradoxical response of sinus bradycardia with accompanying hypertension it should be completed with the use of atropine, if possible, because it may reveal reversible ischemia in the RCA territory Dobutamine may reveal ischemia by increasing the myocardial oxygen demand and, typically, increasing the heart rate.2 However, in some cases, DSE may lead in paradoxical bradycardia with a prevalence of 8%.5 This phenomenon is commonly associated with concomitant hypotension and is attributed to activation of the BezoldJarisch reflex It originates in sensory receptors located in the inferoposterior LV wall and has vagal afferent pathways, promoting bradycardia and vasodilation due to the increase in parasympathetic activity.6 These cardiac receptors are activated by forceful myocardial contraction or chemical substances/drugs The clinical presentation of this reflex has a broad spectrum of bradycardia, hypotension or both Attenhofer et al reported that paradoxical bradycardia during DSE is associated with hypotension in 57% and with a diagnosis of coronary artery disease in 43% of reported cases.5 Of note, none of these patients with bradycardia had a concomitant response of blood pressure elevation By contrast, the current case presents a patient who developed paradoxical bradycardia with a concomitant hypertensive response during DSE, which cannot be assigned to parasympathetic overactivation This phenomenon has been previously described, but DSE was prematurely interrupted and was rendered non-diagnostic7 or it uncovered atrioventricular dissociation.8 In the current case, 88% of the target heart rate was achieved; therefore, DSE was diagnostic for ischemia detection Bradycardia was surpassed by prematurely increasing dobutamine infusion from 20 to 30 mg/kg/min in a instead of 3-minute interval There is lack of evidence that paradoxical bradycardia with concomitant hypertension during DSE, as described in the current report, could be directly associated with ischemia in the RCA territory It has been previously reported that bradycardia during dobutamine perfusion scintigraphy is indicative of inferior wall ischemia.9 However, the study was small (n Z 58) and only 20% had concomitant hypertension.9 Therefore, in the current case, the classical method of new regional wall motion abnormalities was applied to detect ischemia.2 Although there were no regional wall motion abnormalities when the maximum heart rate was achieved, new wall motion abnormalities were detected at the inferior wall during recovery Karagiannis et al suggested that new regional wall motion abnormalities during recovery had a higher sensitivity (98%) for detecting ischemia in patients with single vessel coronary artery disease compared to peak stress (81%).10 Accordingly, the current DSE was reported as positive for ischemia in the RCA territory An episode of syncope with a history of known coronary artery disease should be examined for reversible myocardial ischemia, and DSE should be prominently featured in the cascade of this investigation The presence of paradoxical sinus bradycardia with concomitant hypertension during DSE should not lead to early test interruption and may be considered to be a sign of ischemia in the RCA territory Disclosures None Acknowledgements None References Danad I, Szymonifka J, Twisk JW, et al Diagnostic performance of cardiac imaging methods to diagnose ischaemia-causing coronary artery disease when directly compared with fractional flow reserve as a reference standard: a meta-analysis Eur Heart J 2016 http://dx.doi.org/10.1093/eurheartj/ ehw095 Sicari R, Nihoyannopoulos P, Evangelista A, et al Stress Echocardiography Expert Consensus StatementeExecutive Summary: European Association of Echocardiography (EAE) (a registered branch of the ESC) Eur Heart J 2009;30: 278e289 Eroglu S, Sade LE, Polat E, Bozbas H, Muderrisoglu H Association between coronary flow reserve and exercise capacity Hellenic J Cardiol 2015;56:201e207 Bhattacharyya S, Kamperidis V, Chahal N, et al Clinical and prognostic value of stress echocardiography appropriateness criteria for evaluation of coronary artery disease in a tertiary referral centre Heart 2014;100:370e374 Attenhofer CH, Pellikka PA, McCully RB, Roger VL, Seward JB Paradoxical sinus deceleration during dobutamine stress echocardiography: description and angiographic correlation J Am Coll Cardiol 1997;29:994e999 Mark AL The Bezold-Jarisch reflex revisited: clinical implications of inhibitory reflexes originating in the heart J Am Coll Cardiol 1983;1:90e102 Please cite this article in press as: Kamperidis V, et al., Paradoxical bradycardia and blood pressure elevation during dobutamine stress echocardiography reveal ischemia in a patient with syncope, Hellenic Journal of Cardiology (2016), http://dx.doi.org/10.1016/ j.hjc.2016.11.025 + MODEL Letter to the Editor Olszowska M, Musialek P, Drwila R, Podolec P Progressive bradycardia with increasing doses of dobutamine leading to stress echo interruption Cardiol J 2012;19:79e80 Khan W, Bustros T, Mitre C, Feit A, Salciccioli L, Kassotis J Sinus node dysfunction unmasked during dobutamine stress echocardiography Cardiology 2011;119:7e10 Hopfenspirger MR, Miller TD, Christian TF, Gibbons RJ Sinus node deceleration during dobutamine perfusion scintigraphy as a marker of inferior ischemia Am j cardiol 1994;74: 817e819 10 Karagiannis SE, Bax JJ, Elhendy A, et al Enhanced sensitivity of dobutamine stress echocardiography by observing wall motion abnormalities during the recovery phase after acute beta-blocker administration Am j cardiol 2006;97: 462e465 Vasileios Kamperidis* George Giannakoulas Maria Vlachou Cardiology Department, AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece Stella Ntourtsiou Cardiology Department, AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece Cardiology Department, General Hospital of Komotini, Komotini, Greece Georgios Sianos Haralambos Karvounis Cardiology Department, AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece *Corresponding author Vasileios Kamperidis MD, MSc, PhD, Cardiology Department, AHEPA University Hospital Stilp, Kyriakidi 1, 54636, Thessaloniki, Greece Tel/fax: ỵ30 2310994830 E-mail address: vkamperidis@outlook.com (V Kamperidis) 12 September 2016 Please cite this article in press as: Kamperidis V, et al., Paradoxical bradycardia and blood pressure elevation during dobutamine stress echocardiography reveal ischemia in a patient with syncope, Hellenic Journal of Cardiology (2016), http://dx.doi.org/10.1016/ j.hjc.2016.11.025 ... It originates in sensory receptors located in the inferoposterior LV wall and has vagal afferent pathways, promoting bradycardia and vasodilation due to the increase in parasympathetic activity.6... may reveal reversible ischemia in the RCA territory Dobutamine may reveal ischemia by increasing the myocardial oxygen demand and, typically, increasing the heart rate.2 However, in some cases,... these patients with bradycardia had a concomitant response of blood pressure elevation By contrast, the current case presents a patient who developed paradoxical bradycardia with a concomitant