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J Am Coll Cardiol, 2007; 50:448-452, doi:10.1016/j.jacc.2007.03.050 (Published online 13 July 2007).
© 2007 by the American College of Cardiology Foundation
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CLINICAL RESEARCH: TRANSIENT APICAL BALLOONING

Four-Year Recurrence Rate and Prognosis of the Apical Ballooning Syndrome

Ahmad A. Elesber, MD*, Abhiram Prasad, MD, FACC*, Ryan J. Lennon, MS{dagger}, R. Scott Wright, MD, FACC, FESC*, Amir Lerman, MD, FACC* and Charanjit S. Rihal, MD, FACC*,*

* Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota
{dagger} Division of Biostatistics, Mayo Clinic, Rochester, Minnesota.

Manuscript received January 8, 2007; revised manuscript received March 12, 2007, accepted March 19, 2007.

* Reprint requests and correspondence: Dr. Charanjit S. Rihal, Division of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905. (Email: rihal{at}mayo.edu).


   Abstract
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Methods
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 Discussion
 Conclusions
 References
 
Objectives: This study sought to assess the long-term prognosis of patients with apical ballooning syndrome (ABS).

Background: Apical ballooning syndrome is a recently described acute cardiac syndrome of uncertain etiology and prognosis.

Methods: We retrospectively identified 100 unselected patients with a confirmed diagnosis of ABS by angiography. Recurrences of ABS and mortality were recorded.

Results: Over a mean follow-up of 4.4 ± 4.6 years, 31 patients continued to have episodes of chest pain and 10 patients had recurrence of ABS, for a recurrence rate of 11.4% over the first 4 years. Seventeen patients died in 4.7 ± 4.8 years of follow-up. There was no difference in survival or in cardiovascular survival to an age- and gender-matched population.

Conclusions: The recurrence rate for ABS was 11.4% over 4 years after initial presentation. Recurrence of chest pain is common. Four-year survival was not different from that in an age-matched and gender-matched population.

Abbreviations and Acronyms
  ABS = apical ballooning syndrome
  ECG = electrocardiographic/electrocardiography

Apical ballooning syndrome (ABS) is a recently described acute cardiac syndrome (1). Several series have described the clinical features of the syndrome (2–8). Some reports have described recurrence of ABS (3–6), and a few reports have described the short-term prognosis (5,6). However, most of these series were small cohort studies (2–4,6,7) and none reported the recurrence rate and the long-term prognosis of ABS.

The goal of the current study was to assess the recurrence rate of ABS after initial presentation and the factors associated with ABS recurrence, and the long-term survival of patients with ABS and identification of factors that influence survival with ABS.


   Methods
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Results
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Patients.   This study was approved by the Mayo Foundation Institutional Review Board. We searched the Mayo Cardiac Catheterization Laboratory database from January 1988 through November 2005 for patients who underwent both coronary and left ventricular angiography and met the previously described Mayo Clinic criteria for ABS (1). Our initial search was restricted to patients with coronary artery diameter stenoses <30% and apical hypokinesis, akinesis, or dyskinesis with sparing of the basal segments. This search yielded 545 potential patients; 421 were excluded for other cardiac diagnoses. Of the remaining 124 patients, 102 met the criteria for the clinical identification of ABS (1). Two of these could not be contacted on follow-up. Thus, 100 patients comprised the study population.

The complete medical record and angiographic studies of each patient were reviewed. An ST-segment elevation was defined as deviation >1 mm in amplitude in more than 2 contiguous leads, and deep T-wave inversion was defined as inversions >3 mm in amplitude in at least 3 contiguous leads. All other electrocardiographic (ECG) changes that did not fulfill these criteria were grouped under nonspecific ST/T-wave changes.

A measurement of left ventricular ejection fraction by echocardiography was done according to the Simpson rule (9). Angiography was performed at presentation in 81 patients, on the second day in 12 patients, on the third day in 5 patients, and on the fourth day in 2 patients. A measurement of left ventricular ejection fraction by biplanar contrast left ventriculography was carried out by the monoplane area-length method (10).

Clinical follow-up.   Follow-up data were collected through detailed review of all medical records. Mailed questionnaires and telephone interviews with patients also were used to complete follow-up. For a diagnosis of recurrence, the proposed Mayo criteria for the clinical diagnosis of ABS had to be met with repeat coronary angiography (1). The cause of death was confirmed by review of all available clinical information at the time of death and by review of death certificates.

Statistical analysis.   Continuous data are summarized as mean ± SD unless otherwise noted. Frequencies and percentages are used to describe discrete variables. Kaplan-Meier methods were used to estimate long-term survival. A Poisson model was used to estimate 95% confidence intervals for event rates per person-year. The incidence of recurrence of ABS over time was estimated in a competing risks scenario, with death as the competing event (11). Simple hazard ratios for follow-up mortality were computed using Cox proportional hazards models.

The risk of mortality (total and cardiac) observed in our study cohort was compared with modeling of the expected risk of mortality using data derived by applying age-, gender-, and birth-year–specific mortality rates from the Minnesota white population (12,13) to the age-, gender-, and birth-year–specific person-years of follow-up in this cohort. Population rates were not available after the year 2002, so 2002 rates were carried forward for subsequent years. One-sample log-rank tests were used to compare the observed and expected cardiac event rates (14).


   Results
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Discussion
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Clinical characteristics.   Clinical characteristics for the entire cohort are summarized in Table 1. All 100 study patients were white. Most patients were local residents, with 66 patients living within a 60-mile radius of the hospital, and 92 within a 120-mile radius. Troponin T levels were available for 47 patients and showed elevation in all but 1 patient. A summary of identifiable precipitating events for the ABS is provided in Table 2.


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  		Table 1 Patient Clinical Characteristics
 

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  		Table 2 Precipitating Factors
 
Presentation and hospital outcome.   The most common presentation of patients with ABS was the combination of chest pain, ECG abnormalities, and a mild elevation in cardiac biomarkers.

The left ventricular ejection fraction was depressed at presentation in all patients, with normalization at a median of 69 days from presentation (interquartile range 27 to 348 days). Coronary angiography at initial evaluation indicated a normal left anterior descending artery in 41 patients and mild stenoses (<30%) in 59 patients.

During the index hospitalization, 6 patients had life-threatening arrhythmias: 1 patient presented with a ventricular fibrillation arrest; 1 patient presented with ventricular tachycardia and cardiac arrest; 2 patients presented with second-degree atrioventricular block, 1 of whom subsequently required permanent pacemaker implantation; and 2 patients had asystolic arrest during hospitalization. Two patients died during index hospitalization, both after a cardiac arrest, 1 with ventricular fibrillation and 1 with asystole.

Discharge medications are listed in Table 1. When the population was stratified according to year of presentation (1988 to 1993 vs. 1994 to 1999 vs. 2000 to 2005), use of beta-blockers (17% vs. 44% vs. 74%, p < 0.001), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (17% vs. 36% vs. 64%, p < 0.001), and statins (6% vs. 28% vs. 42%, p = 0.01) increased significantly, whereas the use of aspirin did not change (83% vs. 64% vs. 75%, p = 0.34).

Events occurring during follow-up.   Follow-up information was available for all 100 patients. Most patients were local residents and subsequently returned to Mayo Clinic for their general medical care. The frequency of returns was variable. Data from multiple return visits were available for 84 patients. The other 16 patients were sent questionnaires and contacted by telephone if no response was received.

Recurrence of ABS.   The ABS recurred in 10 patients over a mean follow-up of 4.4 ± 4.6 years. Figure 1 shows the Kaplan-Meier estimated rate of ABS recurrence. The recurrence rate was highest within the first 4 years at about 2.9% per year, subsequently decreasing to about 1.3% per year over the remainder of follow-up. The relatively small number of patients and recurrences did not allow meaningful statistical analysis of factors predicting the recurrence of ABS.


Figure 1
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  		Figure 1 Recurrent Rate of ABS

Kaplan-Meier curve showing recurrence of apical ballooning syndrome (ABS) over time for the total patient population. Number of patients still at risk is noted at 2-year intervals below the time axis.

 
Of note, only 2 patients had an identifiable precipitating event at recurrence (pneumothorax in 1 and significant money loss at the casino in another). The ejection fraction was 38 ± 16%. One patient died at recurrence secondary to ventricular fibrillation arrest.

Medical therapy at the time of last follow-up was not different from that started at the index evaluation for any treatment studied (data not shown). At the time of recurrence of ABS, there was no difference between the patients who did and did not have recurrence in the use of aspirin (60% vs. 67%, p = 0.67), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (60% vs. 51%, p = 0.59), beta-blockers (80% vs. 52%, p = 0.10), and statins (40% vs. 33%, p = 0.67).

Morbidity.   A total of 31 patients continued to experience episodes of chest pain. Of these 31 patients, 12 had chest pain resulting in at least 1 hospital admission, with 3 having repeat coronary angiography showing nonobstructive coronary atherosclerosis. Two patients had progression to severe congestive heart failure requiring in-patient treatment (in 1 case, repeat echocardiography showed normal ejection fraction). Only 1 patient (male) had progression of coronary atherosclerosis requiring bypass surgery more than 16 years after the index presentation.

Mortality.   Seventeen patients died over a mean follow-up of 4.7 ± 4.8 years. Table 3 summarizes the causes of death. Table 4 summarizes univariate models for predictors of death after ABS index presentation. Multivariate analysis was not possible because of the small number of events.


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  		Table 3 Causes of Death
 

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  		Table 4 Univariate Analysis for Predictors of Death After ABS Index Presentation
 
Figure 2 shows the survival estimates of the population, as well as the expected survival for an age-, gender-, birth year-, and race-matched population. Mortality did not differ significantly between our study population and the matched control population. Figure 3 shows the cardiovascular survival estimates of the population, as well as the expected cardiovascular survival for an age-, gender-, birth year-, and race-matched population. Cardiovascular mortality did not differ significantly between our study population and the matched control population.


Figure 2
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  		Figure 2 Survival of Patients With ABS Versus an Age- and Gender-Matched Population

Kaplan-Meier curves showing estimated survival over time. Expected survival of an age- and gender-matched population (expected) is shown along with survival of patients with apical ballooning syndrome.

 

Figure 3
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  		Figure 3 Cardiovascular Survival of Patients With ABS Versus an Age- and Gender-Matched Population

Kaplan-Meier curves showing estimated cardiovascular survival over time. Expected cardiovascular survival of an age- and gender-matched population (expected) is shown along with cardiovascular survival of patients with apical ballooning syndrome.

 

   Discussion
Top
 Abstract
 Methods
 Results
 Discussion
Conclusions
 References
 
This series of 100 patients with ABS clarifies important issues related to the natural history of ABS. First, recurrence of ABS is infrequent. Second, 4-year survival of patients with ABS is similar to the expected survival for an age-, gender-, birth year-, and race-matched population.

Patients with ABS have a presentation similar to that for an acute coronary syndrome. Despite the considerable morbidity with which these patients present, most patients survive the index hospitalization with adequate medical support. In the present report, in-hospital mortality was low (2%) and generally caused by a cardiac arrhythmia. These findings compare favorably with the reported rates of in-hospital mortality of 9% to 10% in nonselected case series of myocardial infarction (15,16).

The recurrence of ABS is infrequent: an average yearly recurrence rate of 2.9% over the first few years after the first event, subsequently decreasing to 1.3% per year over the remainder of follow-up. The relatively small number of recurrences unfortunately precluded further analyses of predictors and outcomes. Although ABS is associated with a hyperadrenergic state (8), beta-blockade did not fully prevent recurrences.

We report 4-year morbidity associated with ABS. Almost one-third of the patients continued to have episodes of chest pain, and up to one-third of these patients required admission for evaluation and management of chest pain (1). In those patients who had repeat coronary angiography, the study showed no progression of atherosclerosis, highlighting the difference in the pathophysiology between chest pain in patients with ABS and patients with typical angina secondary to atherosclerotic heart disease.

Previous reports have commented only on the short-term survival of patients with ABS (3,5,6). In our study, patients with ABS had similar 4-year survival and cardiovascular survival to an age- and gender-matched population. The 4-year prognosis of patients with ABS remains excellent, paralleling the general clinical course of quick symptom resolution.

In our case series, we observed no prognostic value of troponin or B-type natriuretic peptide levels, and the ECG findings at index hospitalization did not predict short-term or long-term survival. These features continue to distinguish ABS from acute coronary syndromes.

Study limitations.   The present study consists of a relatively small cohort of retrospectively identified patients with a rare condition that mimics acute coronary syndrome. Limitations in our analysis include the small number of hard end points, which limits the analysis and the conclusions that can be drawn from this analysis. Treatment of the patients was empirical and may reflect treatment biases for which we cannot account or adjust fully. Other limitations include the lack of systematic measurements of neurohormones and cardiac enzymes; the maximal troponin T value was available in only 47 patients beginning in 2001, although all patients had at least 1 cardiac enzyme set available.


   Conclusions
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 Abstract
 Methods
 Results
 Discussion
 Conclusions
References
 
Data from our case series of ABS cases suggest that recurrence is infrequent. The 4-year prognosis of patients with ABS was similar to that expected in an age- and gender-matched population.


   References
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 Discussion
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 References
 

  1. Bybee KA, Kara T, Prasad A, et al. Systematic review: transient left ventricular apical ballooning: a syndrome that mimics ST-segment elevation myocardial infarction Ann Intern Med 2004;141:858-865.[Abstract/Free Full Text]
  2. Abe Y, Kondo M, Matsuoka R, Araki M, Dohyama K, Tanio H. Assessment of clinical features in transient left ventricular apical ballooning J Am Coll Cardiol 2003;41:737-742.[Abstract/Free Full Text]
  3. Bybee KA, Prasad A, Barsness GW, et al. Clinical characteristics and thrombolysis in myocardial infarction frame counts in women with transient left ventricular apical ballooning syndrome Am J Cardiol 2004;94:343-346.[CrossRef][ISI][Medline]
  4. Desmet WJ, Adriaenssens BF, Dens JA. Apical ballooning of the left ventricle: first series in white patients Heart 2003;89:1027-1031.[Abstract/Free Full Text]
  5. Tsuchihashi K, Ueshima K, Uchida T, et al. Transient left ventricular apical ballooning without coronary artery stenosis: a novel heart syndrome mimicking acute myocardial infarctionAngina Pectoris-Myocardial Infarction Investigations in Japan. J Am Coll Cardiol 2001;38:11-18.[Abstract/Free Full Text]
  6. Sharkey S, Lesser J, Zenovich A, et al. Acute and reversible cardiomyopathy provoked by stress in women from the United States Circulation 2005;111:388-390.[Free Full Text]
  7. Kurisu S, Sato H, Kawagoe T, et al. Tako-tsubo-like left ventricular dysfunction with ST-segment elevation: a novel cardiac syndrome mimicking acute myocardial infarction Am Heart J 2002;143:448-455.[CrossRef][ISI][Medline]
  8. Wittstein IS, Thiemann DR, Lima JA, et al. Neurohumoral features of myocardial stunning due to sudden emotional stress N Engl J Med 2005;352:539-548.[Abstract/Free Full Text]
  9. Folland ED, Parisi AF, Moynihan PF, Jones DR, Feldman CL, Tow DE. Assessment of left ventricular ejection fraction and volumes by real-time, two-dimensional echocardiographyA comparison of cineangiographic and radionuclide techniques. Circulation 1979;60:760-766.[Abstract/Free Full Text]
  10. Walsh W, Falicov RE, Pai AL. Comparison of single and biplane ejection fractions in patients with ischemic heart disease Br Heart J 1976;38:388-395.[Abstract/Free Full Text]
  11. Gooley TA, Leisenring W, Crowley J, Storer BE. Estimation of failure probabilities in the presence of competing risks: new representations of old estimators Stat Med 1999;18:695-706.[CrossRef][ISI][Medline]
  12. Therneau TM, Sicks JD, Bergstralh EJ, Offord JR. Expected Survival Based on Hazard Rates. Rochester, MN: Mayo Clinic, Section of Biostatistics; 1994March. Technical Report Series No. 52.
  13. Centers for Disease Control and Prevention. Wide-ranging OnLine Data for Epidemiologic Research (WONDER). Available at: http://wonder.cdc.gov/mortICD9J.html. Accessed November 8, 2006.
  14. Harrington DP, Fleming TR. A class of rank test procedures for censored survival data Biometrika 1982;69:553-566.[Abstract/Free Full Text]
  15. Rogers WJ, Canto JG, Lambrew CT, et al. Temporal trends in the treatment of over 1.5 million patients with myocardial infarction in the US from 1990 through 1999: the National Registry of Myocardial Infarction 1, 2 and 3 J Am Coll Cardiol 2000;36:2056-2063.[Abstract/Free Full Text]
  16. Mickelson JK, Blum CM, Geraci JM. Acute myocardial infarction: clinical characteristics, management and outcome in a metropolitan Veterans Affairs Medical Center teaching hospital J Am Coll Cardiol 1997;29:915-925.[Abstract]



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