Clinical Features and Outcome of Pheochromocytoma-Induced Takotsubo Syndrome: Analysis of 80 Published Cases

Myriads of physical stress factors including pheochromocytoma have been reported triggering takotsubo syndrome (TS). The aim of this study was to report on the clinical features and outcome of pheochromocytoma-induced TS (Pheo-TS) in a large cohort of patients. Eighty published cases of Pheo-TS were retrieved from the literature and compared with 1,750 cases of all patients with TS (All-TS) published recently by Templin et al. Patients with Pheo-TS were on average 19.87 years younger than those with All-TS (p <0.0001). The women were still predominating in Pheo-TS but significantly in a lower percentage (70% in Pheo-TS vs 89.8% in All-TS, p <0.00001). Almost 1/3 (30%) of Pheo-TS cases had basal TS pattern compared with 2.2% of cases in All-TS (p <0.00001) and 1/5 (20%) had global TS compared with no cases in All-TS. Two thirds of Pheo-TS cases (67.9%) developed complications, which was significantly higher than complication rates in All-TS (21.8%), but there was no difference in the inhospital mortality between the 2 studies. The most important risk factors for the development of complications in Pheo-TS were age <50 years and global and basal TS localization patterns. The recurrence rate of 17.7% in Pheo-TS was significantly higher than the 3.26% in All-TS (p <0.00001). In conclusion, Pheo-TS is characterized by a dramatic clinical presentation with high complication rates and relatively high recurrence rate. Patients with Pheo-TS are significantly younger than All-TS. The TS localization pattern in Pheo-TS differed significantly from All-TS with basal pattern in almost 1/3 of cases and global pattern in 1/5 of the cases.

Takotsubo syndrome (TS), an acute cardiac disease entity, is characterized by a striking left ventricular wall motion abnormality (LVWMA) with a circumferential pattern extending beyond the coronary artery supply region and resulting in a conspicuous ballooning of the left ventricle during systole. Countless physical stress factors have been reported to trigger the disease. Among the physical stressors are the disease processes causing hypercatecholaminemia as pheochromocytoma and paraganglioma. Pheochromocytoma is a catecholamine-secreting tumor that arises from chromaffin tissue of the sympathetic nervous system. Clinical manifestation of pheochromocytoma is highly variable leading to its designation as the disease of “multiple faces” or the “great mimic.” In this report, the clinical features and outcomes of 80 cases of pheochromocytoma-induced TS (Pheo-TS) reported in the literatures ( Supplementary References ) are described and compared with a large study recently reported by Templin et al including all patients with TS (All-TS).


All cases of Pheo-TS from 1990, the year where the Japanese term takotsubo was introduced, to November 2015 are critically reviewed. The cases were retrieved by searching in the PubMed using the search terms “takotsubo,” “apical ballooning,” “stress cardiomyopathy,” and “broken heart syndrome” and linking them with the terms “pheochromocytoma,” “paraganglioma,” and “catecholamines.” For the reasons mentioned in the discussion, cases with pheochromocytoma-induced transient left ventricular dysfunction where the clinical features and course were consistent with TS are also included. Eighty-one cases were retrieved but because of the extreme similarities between 2 reported cases, 1 case that was reported later was excluded. Eighty case reports constitute the patient material of this report. Nine of the cases deemed to be Pheo-TS were reported before the TS-era, with the TS-era is meant the cases reported after 1999 where the first reports on TS were published in English language. Seventy-one cases were reported during TS-era. One case from 1987 with features typical of mid-apical TS was also included. The reports included were published in English language, 1 case in Swedish and 1 in German, where sufficient information could be obtained. In 7 cases, sufficient information could be acquired from only the abstract. The following information was abstracted from the publications: the year of publications, age and gender of the patients, the clinical presentation, the type of electrocardiographic (ECG) changes, and the cardiac biomarkers. The TS localization patterns were deemed by the description in the text or the available figures in the reports. The hemodynamic complication rates after the presentation, the inhospital mortality, the clinical course of the disease, and the recovery and the recurrence rates available were reviewed ( Table 1 ). The results in this study were compared with the 1,750 patients in a recently published study by Templin et al, where all types of TS were included ( Table 2 ) when comparable information were available in both studies. Continuous variables are presented as means ± SDs and categorical data as absolute values and percentages. Fisher’s exact test or chi-square test was used as appropriate to compare categorical data, and 2-tailed unpaired student’s t test was used for continuous variables; a p <0.05 was considered significant.

Table 1

Clinical features on admission, in-hospital complications and outcome in the 80 patients with pheochromocytoma-triggered TS

Authors Year Age Gender Presenting symptoms ECG changes Complications TS localization Recur-rence Other important descriptions and findings
1-Shaw TR 1987 41 M Abdominal pain after an assault STEMI C-Sh Mid-apical 0 Before TS-era, TS not mentioned, Transient shock and myocardial impairment
2- Murai K 1991 42 M Headache, chest pain, palpitation, ST-depression C-Sh Basal or mid-basal 0 Before TS-era: pheochromocytoma with ECG mimicking angina pectoris
3- Salathe M 1992 42 M Cough, tachycardia and hypertension STEMI P-Ed Global 0 Before TS-era, Pheochromocytoma and catecholamine induced cardiomyopathy
4- Quezado ZN 1992 46 F Dyspnea, tachypnea, ST-depression P-Ed Global 0 Before TS-era, described as reversible myocardial depression
5- Elian D 1993 41 M Left flank pain, headache, palpitation and facial flushing T-wave inversion P-Ed Mid-apical 0 Before TS-era, described as reversible catecholamine-induced cardiomyopathy
6- Nanda AS 1995 18 F Agitated with blood pressure elevation, tachycardia and cyanosis S tachyc, T-wave changes P-Ed Mid-apical 0 Before TS-era, pheochromocytoma-induced catecholamine cardiomyopathy
7- Suga K 1996 70 F Cough and low-grade fever, dyspnea and palpitation. S tachyc. P-Ed Global +( two times) Before TS era, described as pheochromocytoma with cardiomyopathy and pulmonary edema
8- Gatzoulis KA (abstract) 1998 45 M Chest pain in the setting of hypertensive crisis Acute ischemia P-Ed Global N/A Before TS-era, described as reversible cardiomyopathy
9- Brilakis ES 1999 43 F Chest pain, dyspnea, diaphoresis, nausea and vomiting STEMI P-Ed, C-Sh and C-A Global 0 Before TS-era: reversible catecholamine-induced cardiomyopathy
10- Dinckal MH (abstract) 2003 44 F Chest pain, headache and nausea T-wave inversion N/A Mid-apical 0 Pheochromocytoma induced myocarditis mimicking acute myocardial infarction
11- Darze ES 2004 46 F Nausea, vomiting, diaphoresis STEMI C-Sh Mid-apical 0 Pheochromocytoma induced segmental myocardial dysfunction mimicking AMI
12- Spes C 2006 56 F Chest pain associated with hypertension T-wave inversion 0 Mid-apical + Takotsubo-like left ventricular dysfunction (apical ballooning)
13- Otsuka M 2006 63 F Substernal chest pain STEMI 0 Mid-apical 0 Left ventricular apical ballooning
14- Grinda JM 2006 49 M Abdominal pain, vomiting, headache and malaise Nonspecific changes P-Ed, C-A, C-Sh and multiple organ failure Global 0 Under TS-era: unusual cardiogenic shock due to pheochromocytoma
15- Sanchez-Recalde A 2006 41 F Headache, psychomotor agitation, diaphoresis, nausea and vomiting ST-depression C-A, EMD and respiratory deterioration Mid-basal 0
16- Van Spall HG 2007 43 F Chest tightness, palpitation, light-headedness, and sweating Deep T-wave inversion 0 Mid-apical 0
17- Takizawa M 2007 32 M Chest pain and back pain ST-depression HF Mid-basal 0 Left ventricular end-diastolic pressure 26 mm Hg
18- Kim HS 2007 47 M Headache, palpitation and dyspnea ST-depression P-Ed, C-Sh and circulatory failure Mid-basal 0
19- Brukamp K 2007 52 F Fever, nausea, emesis, and diffuse abdominal pain ST-depression C-Sh, P-Ed and RF Mid-basal 0 Rapidly reversible cardiogenic shock
20- Di Valentino M 2008 52 F Chest pain, dyspnea, hypertensive crisis, and headache ST-depression 0 Mid-basal 0 —-
21- Kim EM 2008 32 M Palpitation with squeezing chest pain STEMI 0 Mid-basal 0 Text: echocardiography midventricular dilatation but on LV angio mid-basal.
22- Pfister R 2008 59 F Chest pain and dyspnea T-wave inversion 0 Mid-basal +(5 times) Recurrence for the fifth time with different contractile patterns
23- Barriales-vill R 2008 41 F Anginal chest pain STEMI 0 Mid-ventricular 0
24- Zegdi R 2008 51 F Symptoms of respiratory failure, tachycardia and hypertension ST-depression RF, P-Ed C-Sh, EMD, and metabolic acidosis Mid-basal 0
25- de Souza F 2008 31 F Precordial pain, associated with palpitation and hypertensive crisis STEMI HF Mid-apical 0
26- Mrdovic I 2008 53 F Anginal chest pain after intense emotional stress STEMI LV thrombus, LVOT obstruction Mid-apical 0
27- Lassnig E 2009 71 F Syncope, nausea, vomiting and hypotension. chest pain S tachyc C-Sh, P-Ed, multi-organ failure, fever and death Mid-apical + Recurrence, multiple complications and death
28- Zhou W 2009 43 F Rapidly progressive dyspnea, and tachycardia STEMI VT, HF, Thrombo-embolism Apical + Concurrent pheochromocytoma, VT, LV thrombus, and systemic embolization
29- Cho DK 2009 45 F Saturation dropped with tachycardia, tachypnea and hypoxia T-inversion P-Ed Mid-ventricular 0
30- Jindal V 2009 55 M Palpitation, chest pain and headache ST-depression P-Ed, C-Sh, RF Mid-basal 0
31- Jang SY 2009 62 F Dizziness during recurrence, Increased BP during the first attack T-inversion 0 Mid-apical + The first attack manifested with increased BP during anesthesia, mid-basal pattern
32- Rossi AP (abstract) 2009 81 F Chest discomfort STEMI HF Apical + The first attack was of unknown localization
33- von Bergen NH 2009 17 M Emesis, hypertension and difficulty in maintaining balance STEMI P-Ed Mid-apical 0
34- Cesaretti M (abstract) 2010 N/A F Abdominal and chest pain, headache, nausea and sweating STEMI 0 Mid-apical 0
35- Tanriver Y 2010 57 M Chest and epigastric pain, repeated vomiting, and dyspnea STEMI P-Ed Mid-apical 0 In this case, sepsis may have been the trigger factor
36- Kim S 2010 30 M Severe suprapubic and left lower abdominal pain ST-depression P-Ed Mid-basal 0
37- Zielen P 2010 53 M Chest pain, dyspnea, epigastric discomfort, nausea and vomiting STEMI 0 Mid-apical 0
38- Marcovitz PA 2010 43 F Waxing and waning headache, palpitation and chest pain STEMI 0 Mid-apical 0
39- Kimura S 2010 36 F Dyspnea and shock, high BP ST-depression, tall T-wave Shock and P-Ed Mid-basal 0
40- Gujja KR 2010 46 F Chest pain, tightness palpitation, sweating and dyspnea STEMI 0 Mid-apical 0
41- Di Palma G 2010 29 F Dyspnea, orthopnea and vomiting Nonspecific changes P-Ed and C-Sh Mid-basal +(twice) Two recurrences, the second of the same type, the third was unclear
42- Kumar S 2010 57 F Headache, vomiting, chest discomfort and palpitation S tachyc and LBBB P-Ed, C-Sh and metabolic acidosis Mid-basal 0
43- Ueda H 2011 86 M Abdominal fullness, diagnosed as ileus and ileus tube was inserted STEMI Death Mid-apical 0 (died) Died due to pneumonia Pathology: catecholamine-induced cardiomyopathy.
44- Zinnamosca L (abstract) 2011 72 F Chest pain associated with high BP Non-STEMI N/A Mid-apical 0
45- Roghi A 2011 64 F Breathlessness, dizziness, and palpitation ST-depression 0 Focal 0 Described as adrenergic myocarditis but all the findings argue for TS
46- Chia PL 2011 69 F Chest pain, dyspnea, diaphoresis, epigastric pain and palpitation STEMI 0 Mid-apical 0
47- Verrijcken A 2011 62 F Headache and scotoma and then dizziness and drowsiness STEMI P-Ed, C-Sh and LV-thrombo-embolisnm Mid-apical 0
48- Park JH 2011 41 M Dyspnea S tachyc P-Ed Mid-basal 0
49- Park JH 2011 49 F Dyspnea, chest discomfort, palpitation and recurrent headache S tachyc P-Ed and hypoxia Global 0
50- McEntee RK 2011 43 F Chest pressure, nausea, vomiting, dyspnea, palpitation, diaphoresis T-wave inversion C-Sh Global 0 Severe dilated cardiomyopathy in undiagnosed adrenal pheochromocytoma
51- Subramanyam S 2012 60 M Chest pain, palpitation, headache and episodes of diaphoresis STEMI 0 Mid-apical + The recurrence had the same TS pattern
52- Celebi H (abstract) 2012 66 F Chest pain STEMI 0 Apical + The first episode of TS was of the same localization as the index presentation
53- Park JY 2012 28 F Chest discomfort ST-depression 0 Mid-basal 0
54- Banfi C 2012 20 F Chest pain, severe dyspnea, cough and hyperthermia ST-depression P-Ed and refractory shock Global 0 The TS localization was described in the text as severe LVD
55- Santoro F 2012 17 F Epigastric pain, headache, agitation, nausea and vomiting STEMI 0 Mid-apical 0
56- Naderi N 2012 31 F Palpitation, fatigue, dyspnea, headache, diaphoresis, high BP ST-depression HF Mid-basal 0 The patient was improved on the second day
57- Demircelik MB 2013 64 M Chest pain and palpitation STEMI 0 Mid-apical 0 Very short case report
58- Kashioulis P (Swedish) 2013 39 F Palpitation, shoulder pain, nausea and profuse sweating S tachyc P-Ed, C-Sh, RF and Biventricular svikt Global 0 Pregnant patient: pheochromocytoma is a life threatening cause of heart failure
59- Kaese S 2013 43 M Polymorph VT Polymorph VT Polymorph VT, refractory HFand C-Sh Global + First attack, mid-apical; the present, severe impairment of LV function
60- Law C 2013 23 F Intractable vomiting and acute chest pain Tachycardia (arrhythmia) Arrhythmia, P-Ed, C-Sh and biventricular failure Global 0 The TS localization was described as severe biventricular failure
61- Iio K 2013 29 F Severe dyspnea and shock ST-depression P-Ed, C-Sh, RF, coma and metabolic acidosis Mid-basal 0
62- Battimelli A 2014 63 F Chest pain, resting dyspnea and peripheral coldness STEMI P-Ed, Right tibial artery embolization Mid-apical 0
63- Kobayashi Y 2014 N/A F Chest pain T-wave inversion 0 Apical or mid-apical 0
64- Jozwik-Plebanek K 2014 32 F Postoperative headache and shortness of breath N/A P-Ed, C-Sh, C-A, and stroke Mid-apical 0
65- Cho SK 2014 45 M Chest pain Tall peaked T-wave 0 Basal 0
66- Pereira-da-Silva T 2014 41 F Cardiogenic shock S tachyc C-Sh Global + The first attack, during pregnancy complicated by pulmonary edema
67-Satendra M 2014 40 M Cough, dyspnea, constricting chest pain, pallor and profuse sweating S tachyc and long QT interval HF Global 0
68- Saporito F 2014 32 M Palpitation, sweating, and effort dyspnea Nonspecific ST-T changes 0 Global 0 Described as acute heart failure due to pheochromocytoma crisis
69- Zhu D 2014 67 F Dizzines, vomiting, stomache, chest pain and dyspnea STEMI P-Ed, C-Sh and metabolic acidosis Mid-apical 0 Multiple complications (tachycardia, tachypnea, hypoxia, acidosis, fever)
70- Flam B 2014 46 F Abdominal pain, dyspnea, nausea and vomiting ST-depression P-Ed, C-Sh, C-A, RF, stroke, metabolic acidosis, and biventricular F Mid-basal 0 Mid-basal TS progresses to severe global biventricular failure
71- Gervais MK 2015 26 M Right abdominal flank pain, diarrhea and vomiting Non-specific T-wave abnormality Hypertensive crisis and EMD Mid-basal 0
72- Kounatiadis P 2015 33 F Dizziness, profuse sweating and increased BP STEMI Bred QRS tachycardia and SVT Global 0 Deemed as global due to diffuse myocardial hypokinesia
73- Brugts JJ 2015 75 F Chest pain ST-depression 0 Mid-basal + The recurrence was 2 years later and of the same pattern (mid-basal)
74- Y-Hassan S 2015 68 F Chest pain T-wave inversion HF and ischemic stroke during recurrence Mid-apical + The recurrence was of the same TS localization pattern
75- Sharkey SW 2015 16 M Chest pain STEMI 0 Mid-ventricular 0
76- Sharkey SW 2015 66 M Acute hypertension, tachycardia, and symptoms of pulmonary edema ST-depression P-Ed and RF Basal 0
77- Ibrahim M 2015 39 F Chest pain associated with diaphoresis and syncope STEMI P-Ed, C-Sh and RF Mid-apical 0
78- Yang TH 2015 54 F Chest tightness, cold sweating, upper back pain, and palpitation STEMI 0 Mid-apical 0 Recurrent pheochromocytoma in the left adrenal with liver metastases
79- Tagawa M 2015 33 F Headache, palpitation, chest pain, fatigue and dyspnea T-wave inversion Hemodynamic compromise, low BP Mid-ventricular 0
80- Assefa D English abstract 2015 42 F Symptoms and signs of cardiogenic shock ST-depression C-Sh, P-Ed, RF, hypertensive crisis Mid-basal 0 Presented with cardiogenic shock

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Nov 26, 2016 | Posted by in CARDIOLOGY | Comments Off on Clinical Features and Outcome of Pheochromocytoma-Induced Takotsubo Syndrome: Analysis of 80 Published Cases

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