Clinical Profile of Patients With High-Risk Tako-Tsubo Cardiomyopathy Scott W. Sharkey, MDa,*, Victoria R. Pink, RNb, John R. Lesser, MDa, Ross F. Garberich, MSa, Martin S. Maron, MDc, and Barry J. Maron, MDa,b Although tako-tsubo cardiomyopathy (TTC) is regarded as a reversible condition with favorable outcome, a malignant clinical course evolves in some subjects. In this singleinstitution experience, we describe the clinical profile of patients with adverse TTC outcome. A cohort of 249 consecutive patients with TTC was interrogated for those with acute unstable presentation during the first 24 hours. Forty-seven patients (19%) experienced early complicated clinical course with cardiac arrest in 9 (ventricular fibrillation, n [ 4, pulseless electrical activity, n [ 3, and asystole, n [ 2) or marked hypotension in 38 (systolic blood pressure £90 mm Hg requiring vasopressors and/or balloon pump). Of the 47 patients, Killip class III to IV heart failure was present in 30 (64%). Despite treatment, 8 patients (3%; all women) died inhospital due to respiratory failure, cardiogenic shock, or anoxic brain injury. All 8 inhospital deaths occurred among the 47 patients with unstable presentation, including 2 after cardiac arrest and 6 with marked hypotension. Post-TTC event mortality for a period of 4.7 – 3.4 years significantly exceeded that in a matched general US population (standardized mortality ratio 1.4; 95% confidence interval 1.1 to 1.9; p [ 0.005) largely due to noncardiac co-morbidities. In conclusion, contrary to widespread perception, TTC is not an entirely benign and reversible condition. Among this large cohort, a high-risk subgroup was identified with cardiac arrest or hemodynamic instability, accounting for all hospital deaths. Hospital nonsurvivors had a variety of irreversible comorbid conditions with the potential to compromise clinical status and adversely affect short-term survival. Long-term survival after hospital discharge was also reduced compared with the general population because of noncardiac co-morbidities. Ó 2015 Elsevier Inc. All rights reserved. (Am J Cardiol 2015;-:-e-)
Tako-tsubo (stress) cardiomyopathy (TTC) is a distinctive cardiac condition with unique left ventricular (LV) contraction profile, often triggered by stressful events, which has been considered reversible and associated with favorable outcome.1e8 However, our experience in a large, single-institution cohort has suggested that this benign characterization of TTC may not be as consistent as previously regarded.5 Therefore, we report here a high-risk subset of TTC patients with malignant clinical presentation. Such observations provide a more robust profile of the TTC clinical spectrum, useful in guiding effective management strategies for patients with this complex but incompletely understood condition. Methods From August 2001 to March 2012, 249 consecutive patients presented with a first TTC event to the Minneapolis Heart a Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, Minnesota; bThe Hypertrophic Cardiomyopathy Center, Minneapolis Heart Institute Foundation, Minneapolis, Minnesota; and c Division of Cardiology, Tufts Medical Center, Boston, Massachusetts. Manuscript received March 28, 2015; revised manuscript received and accepted May 20, 2015. See page 7 for disclosure information. This study was funded by the Minneapolis Heart Institute Foundation, Minneapolis, MN. *Corresponding author: Tel: (612) 863-7372; fax: (612) 863-6441. E-mail address: [email protected] (S.W. Sharkey).
0002-9149/15/$ - see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjcard.2015.05.054
Institute at the Abbott Northwestern Hospital (Minneapolis, Minnesota). As previously described,4 patients with TTC shared the following features: (1) acute presentation typically with chest pain/discomfort or dyspnea, (2) systolic dysfunction with marked LV contraction abnormality, extending beyond the geographic territory of a single coronary artery, assessed with contrast LV angiography, cardiovascular magnetic resonance imaging (CMR), or 2-dimensional echocardiography, (3) absence of obstructive coronary stenosis (i.e., 50% luminal narrowing of the major coronary arteries by angiography) or evidence of acute plaque rupture. The left anterior descending coronary artery was carefully examined since myocardial ischemia in this distribution can cause an LV contraction abnormality mimicking TTC9, (4) absence of myocarditis or ischemic transmural late gadolinium enhancement on CMR. The magnitude of acute heart failure was quantitated using the Killip classification.10 Selected data from 136 study patients have been published previously.1,4 On admission, the ejection fraction (EF) and LV contraction pattern were assessed by LV angiography (n ¼ 149), 2-dimensional echocardiography (n ¼ 95), CMR (n ¼ 2), computed tomography angiography (n ¼ 2), or nuclear imaging (n ¼ 1). LV contraction patterns were categorized: “apical ballooning” (abnormal contraction of mid and apical LV segments), “midventricular ballooning” (abnormal contraction limited to the mid-LV segments), and “basal ballooning” (abnormal contraction limited to the basal LV segments). CMR imaging was performed after admission www.ajconline.org
2
The American Journal of Cardiology (www.ajconline.org)
Figure 1. Flow diagram showing acute clinical status and outcome at hospital discharge in 249 patients with TTC events. * Requiring administration of vasopressor agents and/or IABP. CHF ¼ congestive heart failure; No. ¼ number.
(n ¼ 154) at the discretion of the attending cardiologist. Details of CMR imaging methods have been recently published.4 Two-dimensional echocardiography included analysis of LV and right ventricular (RV) wall motion, degree of mitral regurgitation, and mitral valve systolic anterior motion (SAM). Left ventricular outflow tract gradients were estimated with continuous wave Doppler. Post-hospital EF was measured with echocardiography or CMR. The clinical status of the 249 study patients after the TTC event was assessed as of September 1, 2014, by telephone interview, clinic visit, review of electronic medical records, or interrogation of the US Social Security Death Index. Follow-up was achieved for 233 patients (94%) for a period of 4.7 3.4 years (median 4.2; range 0.1 to 12.8 years). For patients with TTC discharged from the hospital after the initial event, the fraction surviving at each follow-up time was estimated using the Kaplan-Meier method. The expected fraction surviving at each time was computed by assigning to each patient the probability of surviving after presentation, appropriate to patient age at diagnosis and gender, and based on the US Census data. Actual and expected surviving fractions were compared using the 1sample log-rank test, which also provides an estimate and confidence interval (CI) for the standardized mortality ratio and 95% CI. All computations used the “survival” package (version 2.34-1) of the R Software System, version 2.7.2 R (Development Core Team 2008, R Foundation for Statistical Computing, Vienna, Austria). Data are displayed as mean and SD for continuous variables with number and percentage for categorical variables. Categorical variables were analyzed using the
Table 1 Clinical features of 249 tako-tsubo patients with or without acute unstable clinical presentation Variable
With (n ¼ 47)
Without p-value (n ¼ 202)
Age (years) 67 14 68 13 0.85 Male 8 (17%) 7 (3%) < 0.001 Heart rate (beats/minute) 103 28 92 22 0.004 Ejection fraction (%) 25 9 33 10 < 0.001 Peak troponin (ng/ml) 0.84 0.98 0.49 0.47 0.016 Beta-blocker (pre-admission) 13 (28%) 45 (22%) 0.39 Diabetes mellitus 4 (9%) 29 (14%) 0.31 History of systemic hypertension 20 (43%) 115 (57%) 0.13 Current smoker 14 (30%) 33 (16%) 0.022 ST-segment elevation (admission ECG) 23 (49%) 74 (37%) 0.12 Physical stressor 31 (66%) 82 (41%) 0.002 LV apical ballooning 27 (57%) 116 (57%) 0.47 LV mid-ventricular ballooning 18 (38%) 83 (41%) LV basal ballooning 2 (4%) 3 (2%) Length of hospital stay (days) 13 12 55 < 0.001 Hospital mortality 8 (17%) 0 < 0.001 ECG ¼ electrocardiogram; LV ¼ left ventricular.
Pearson’s chi-square or Fisher’s exact tests. Continuous variables were assessed using the Student’s t test. A value of p
Tako-tsubo (stress) cardiomyopathy (TTC) is a distinctive cardiac condition with unique left ventricular (LV) contraction profile, often triggered by stressful events, which has been considered reversible and associated with favorable outcome.1e8 However, our experience in a large, single-institution cohort has suggested that this benign characterization of TTC may not be as consistent as previously regarded.5 Therefore, we report here a high-risk subset of TTC patients with malignant clinical presentation. Such observations provide a more robust profile of the TTC clinical spectrum, useful in guiding effective management strategies for patients with this complex but incompletely understood condition. Methods From August 2001 to March 2012, 249 consecutive patients presented with a first TTC event to the Minneapolis Heart a Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, Minnesota; bThe Hypertrophic Cardiomyopathy Center, Minneapolis Heart Institute Foundation, Minneapolis, Minnesota; and c Division of Cardiology, Tufts Medical Center, Boston, Massachusetts. Manuscript received March 28, 2015; revised manuscript received and accepted May 20, 2015. See page 7 for disclosure information. This study was funded by the Minneapolis Heart Institute Foundation, Minneapolis, MN. *Corresponding author: Tel: (612) 863-7372; fax: (612) 863-6441. E-mail address: [email protected] (S.W. Sharkey).
0002-9149/15/$ - see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjcard.2015.05.054
Institute at the Abbott Northwestern Hospital (Minneapolis, Minnesota). As previously described,4 patients with TTC shared the following features: (1) acute presentation typically with chest pain/discomfort or dyspnea, (2) systolic dysfunction with marked LV contraction abnormality, extending beyond the geographic territory of a single coronary artery, assessed with contrast LV angiography, cardiovascular magnetic resonance imaging (CMR), or 2-dimensional echocardiography, (3) absence of obstructive coronary stenosis (i.e., 50% luminal narrowing of the major coronary arteries by angiography) or evidence of acute plaque rupture. The left anterior descending coronary artery was carefully examined since myocardial ischemia in this distribution can cause an LV contraction abnormality mimicking TTC9, (4) absence of myocarditis or ischemic transmural late gadolinium enhancement on CMR. The magnitude of acute heart failure was quantitated using the Killip classification.10 Selected data from 136 study patients have been published previously.1,4 On admission, the ejection fraction (EF) and LV contraction pattern were assessed by LV angiography (n ¼ 149), 2-dimensional echocardiography (n ¼ 95), CMR (n ¼ 2), computed tomography angiography (n ¼ 2), or nuclear imaging (n ¼ 1). LV contraction patterns were categorized: “apical ballooning” (abnormal contraction of mid and apical LV segments), “midventricular ballooning” (abnormal contraction limited to the mid-LV segments), and “basal ballooning” (abnormal contraction limited to the basal LV segments). CMR imaging was performed after admission www.ajconline.org
2
The American Journal of Cardiology (www.ajconline.org)
Figure 1. Flow diagram showing acute clinical status and outcome at hospital discharge in 249 patients with TTC events. * Requiring administration of vasopressor agents and/or IABP. CHF ¼ congestive heart failure; No. ¼ number.
(n ¼ 154) at the discretion of the attending cardiologist. Details of CMR imaging methods have been recently published.4 Two-dimensional echocardiography included analysis of LV and right ventricular (RV) wall motion, degree of mitral regurgitation, and mitral valve systolic anterior motion (SAM). Left ventricular outflow tract gradients were estimated with continuous wave Doppler. Post-hospital EF was measured with echocardiography or CMR. The clinical status of the 249 study patients after the TTC event was assessed as of September 1, 2014, by telephone interview, clinic visit, review of electronic medical records, or interrogation of the US Social Security Death Index. Follow-up was achieved for 233 patients (94%) for a period of 4.7 3.4 years (median 4.2; range 0.1 to 12.8 years). For patients with TTC discharged from the hospital after the initial event, the fraction surviving at each follow-up time was estimated using the Kaplan-Meier method. The expected fraction surviving at each time was computed by assigning to each patient the probability of surviving after presentation, appropriate to patient age at diagnosis and gender, and based on the US Census data. Actual and expected surviving fractions were compared using the 1sample log-rank test, which also provides an estimate and confidence interval (CI) for the standardized mortality ratio and 95% CI. All computations used the “survival” package (version 2.34-1) of the R Software System, version 2.7.2 R (Development Core Team 2008, R Foundation for Statistical Computing, Vienna, Austria). Data are displayed as mean and SD for continuous variables with number and percentage for categorical variables. Categorical variables were analyzed using the
Table 1 Clinical features of 249 tako-tsubo patients with or without acute unstable clinical presentation Variable
With (n ¼ 47)
Without p-value (n ¼ 202)
Age (years) 67 14 68 13 0.85 Male 8 (17%) 7 (3%) < 0.001 Heart rate (beats/minute) 103 28 92 22 0.004 Ejection fraction (%) 25 9 33 10 < 0.001 Peak troponin (ng/ml) 0.84 0.98 0.49 0.47 0.016 Beta-blocker (pre-admission) 13 (28%) 45 (22%) 0.39 Diabetes mellitus 4 (9%) 29 (14%) 0.31 History of systemic hypertension 20 (43%) 115 (57%) 0.13 Current smoker 14 (30%) 33 (16%) 0.022 ST-segment elevation (admission ECG) 23 (49%) 74 (37%) 0.12 Physical stressor 31 (66%) 82 (41%) 0.002 LV apical ballooning 27 (57%) 116 (57%) 0.47 LV mid-ventricular ballooning 18 (38%) 83 (41%) LV basal ballooning 2 (4%) 3 (2%) Length of hospital stay (days) 13 12 55 < 0.001 Hospital mortality 8 (17%) 0 < 0.001 ECG ¼ electrocardiogram; LV ¼ left ventricular.
Pearson’s chi-square or Fisher’s exact tests. Continuous variables were assessed using the Student’s t test. A value of p
