04/05/03

 

 

 

 

 

 

 
   

Contents | Director | Case 1 | Case 2 | Review 1 | Review 2 | EKG 1 | Rad 1

AMR - March 2004

   

 

 

Case Report -
A 66-year-old woman with hypertension and chest pain

Luiz Coelho, MD

INTRODUCTION

A novel heart syndrome mimicking acute myocardial infarction was originally introduced by Satoh et al. and Dote et al.1, 2 to describe a reversible LV apical wall motion abnormality with chest symptoms.  Some of the features of this myocardial syndrome include electrocardiographic changes (ST elevation or depression, T-wave inversion, and abnormal Q-wave) and small elevation of myocardial enzymes in conjunction with no evidence of obstructive coronary artery disease. This apical wall abnormality has been associated with vasospastic disease, stunning of the apical myocardium, acute myocardial infarction, and systemic disorders such as hypertrophic cardiomyopathy, subarachnoid hemorrhage, gastrointestinal bleeding, and pheochromocytoma.   Furthermore, cases of left ventricular outflow tract obstruction (in the setting of concentric LV hypertrophy) have also been observed to contribute to the development of apical dyskinesis. 

Described here is a patient exhibiting acute onset chest discomfort, abnormal electrocardiogram, cardiac enzymes elevation, non-obstructive coronary disease, and regional wall motion abnormality with ballooning of the myocardial apex.  These manifestations are likely secondary to apical stunning.

CASE REPORT

A 66-year-old Hispanic woman with hypertension presented complaining of intermittent, crushing, non-radiating, substernal discomfort of 3 days duration.  The event occurred both on exertion and at rest, and lasted approximately 10-20 minutes.  Associated symptoms included dyspnea and nausea.  The patient denied tobacco use, alcohol or drug abuse.  Diabetes mellitus, hyperlipidemia and other risk factors for ischemic heart disease could not be accounted for.  She described no previous cardiac events or cardiac workup. 

Physical examination was unremarkable, except for presence of bi-basilar crepitus on lung auscultation.  A 12-lead electrocardiogram revealed normal sinus rhythm, symmetrical T-wave inversion with QT prolongation (QTc, 476 milliseconds), and ST-segment elevations in inferior and lateral wall leads (Fig. 1).   Chest roentgenogram indicated moderate cardiomegaly, and mild bi-basilar congestion.  Initial cardiac injury profile displayed CPK=82 IU/liter, CK-MB=4 IU/liter, and Troponin I=1.9 IU/liter; subsequent CPKs, CK-MBs, and Troponins quickly reached peak values of 139, 13, and 24 (IU/liter), respectively.  Other laboratory studies were only remarkable for a 4.5-fold increase (from reference range) in eosinophil and a normocytic normochromic anemia.  Echocardiographic images suggested distal septal and apical left ventricular hypokinesia.  Overall, the study showed moderately reduced LV ejection fraction, mild aortic, tricuspid, and mitral regurgitation.  Doppler examination of the LV outflow tract demonstrated a normal peak gradient and the absence of any dynamic obstruction.  Coronary angiography findings established no significant, fixed obstructive lesions in the coronary arteries (Fig.2).    As with echocardiography, a left ventriculogram (Fig. 3) also demonstrated a large apical wall motion abnormality.  Left ventricular ejection fraction was estimated at 35-40 percent with normal left ventricular end-diastolic pressure.  Nuclear perfusion imaging only exhibited mild ischemia of the LV apex.    

At two weeks follow-up, the patient demonstrated excellent recovery.   Serial electrocardiograms showed resolution of the T-wave abnormality with normalization of the QT interval.  Cardiac injury profile returned to reference ranges and the initial eosinophilia completely disappeared.  Repeat echocardiography revealed normalization of wall motion and LV function.  A Left Ventricular Cineangiographic study (Fig. 4) confirmed both a complete resolution of the apical wall motion oddity and a restored, normal systolic function. 

Figure 1. Admission ECG

See larger view of EKG

 

Figure 2A.

 

Figures 2B.

Figures 2A, 2B.   Coronary angiography demonstrating no significant, fixed, obstructive lesions in RCA (Fig. 2A) and LAD (Fig. 2B).

   

Figure 3A.

 

Figures 3B.

Figures 3A, 3B. Left Ventricular Cineangiogram during systole (Fig. 3A) and diastole (Fig. 3B) demonstrating asymmetrical regional wall motion abnormality with ballooning of the myocardium.

   

Figure 4A.

 

Figures 4B.

Figures 4A, 4B. Left Ventricular Cineangiogram during systole (4A) and diastole (4B) showing a restored, normal systolic function with disappearance of the apical ballooning 2 weeks after hospital discharge.

DISCUSSION

This case depicts a patient with new-onset chest pain, ECG changes and cardiac enzymes elevation (both consistent with an acute myocardial infarction), and a focal, hypokinetic apical wall motion with ballooning in the absence of obstructive coronary artery disease or hypertrophic cardiomyopathy.  On follow-up, the LV function and wall motion abnormality had completely normalized.  While several cases of this syndrome were described in Japan,1-4 only a few cases have been noted in the US.  Yet, the exact clinical attributes and etiologic basis of the syndrome still remain uncertain primarily due to lack of a comprehensive clinical study.  

Several physical, psychological, and pathophysiologic mechanisms have been studied to account for the development of this transient LV apical ballooning. Tsuchihashi et al.5 performed a multi-center, retrospective study in which his team analyzed 88 confirmed cases of transient apical ballooning.  The results were surprising in that a greater proportion of subjects (27%) had some sort of significant psychological stressor at onset of symptoms (such as sudden accidents, death in family, alcohol intake, vigorous excitation, etc.). Also noteworthy was that there was a much higher proportion of women (76:12 ratio, approximately 6.3-fold higher incidence) than seen in men with this heart syndrome.  Although no clear female dominance can be established from this study, Tsuchihashi’s investigations did recognize a relation to several other exacerbating systemic disorders such as cerebrovascular accidents, epilepsy, bronchial asthma, renal or urinary tract disease, acute abdomen, and non-cardiac surgery or medical procedures.

His study also identified key presenting features at onset of the syndrome.  Chest pain/discomfort was reported in 67% of the subjects while 90% demonstrated electrocardiographic abnormalities (ST elevation or depression, abnormal Q-wave, and T-wave inversion).   Elevated enzymes were also documented in some patients.  It is important to note that none of the patients had significant obstructive epicardial coronary artery disease at presentation.  These observations suggest that this clinical syndrome, with chest symptoms and ECG changes : (1) can easily pose as a typical acute myocardial infarction; (2) often has a distinct temporal relationship with intense emotional stressors; (3) may be improperly diagnosed when it occurs in the absence of predisposing angina or chest pain/discomfort; and (4) may lead to excellent recovery when appropriate, conservative therapeutic interventions are initiated during the acute phase of the syndrome.

While this patient’s clinical features closely resemble those described in the literature, an important difference subsists: no clear temporal relationship with intense emotional stress could be identified.  In other words, the patient’s chest discomfort was not related to an intense emotional load, nor was it related to severe, fixed obstructive disease of the coronary arteries.  Her chest symptoms, however, suggest angina pectoris due to myocardial ischemia, but of a different mechanism.  The possibility of decreased myocardial perfusion due to coronary vasospasm or coronary emboli has been entertained, since it is well-known that both of these coronary maladies can account for total obstruction of coronary blood flow for a sufficiently long time to result in myocardial infarction in patients without coronary artery disease.

Although the precise etiologic basis of transient apical ballooning could not be identified from Tsuchihashi’s study, several scenarios that may conceivably produce the sequence of events were described.

Stunned myocardium has been described as a reversible, post-ischemic process that causes transient depression of myocardial function.  After brief, non-severe ischemic insult, both myocardial necrosis and a shift between myocardial oxygen supply and demand cause an interference of normal LV function.  Biochemical and ultra-structural changes occurring within the myocardial cell (glycogen depletion, clumping and margination of nuclear chromatin, mild inter-myofibrillar and mitochondrial edema, and declining ATP concentrations) all lead to initial cessation of contractile activity of the ischemic zone.    Instead of normal systolic thickening of the LV wall, ischemic muscle zones thin during ventricular contraction.6  Thereafter, the region bulges passively with each systole leading to the apical ballooning phenomenon.  The recovery of cardiac function after a brief episode of ischemia seems to parallel the recovery of ATP (re-synthesis)7, 8 but other factors such as abnormalities in calcium flux, may also be responsible for the prolonged contractile abnormality.   ATP re-synthesis has been demonstrated to resolve within 7 days in the post-ischemic myocardium.   Thus, complete myocardial function cannot be expected to occur immediately after cessation of an ischemic event. The clinical significance of stunned myocardium is that the evaluation of cardiac performance soon after relief of ischemia may not provide adequate assessment of ventricular function.    Proper assessment may be obtained 1-2 weeks after the cardiac insult.9  Furthermore, since post-ischemic depression of myocardial function may require days until complete recovery occurs, the administration of inotropic agents provides sufficient support for improvement of left ventricular performance.

Multiple, diffuse coronary artery spasm has also been postulated as a possible mechanism leading to myocardial ischemia.  In this setting, coronary vasospasm can account for total obstruction of coronary blood flow for a time sufficiently long enough to result in transient focal ischemia or myocardial infarction. Enhanced sympathetic activity is another cause of myocardial damage.  Excessive adrenergic discharge has been demonstrated to cause transient spasm of the epicardial vessels, producing myocyte injury10 with subsequent ballooning of the myocardial apex.  A likely explanation for this injury is that since the apex has a greater adrenoceptor density, LV function is more vulnerable to ischemic injury in this region. Ricci et al.11 documented acute reversal of coronary spasm by administration of an alpha-adrenergic antagonist agent (Phentolamine).  Other investigators demonstrated the role of sympathectomy in the reversal of vasospasm produced by excessive adrenergic discharge.12    Catecholamine-induced cardiomyopathy during the endocrine crisis of pheochromocytoma has also been known to cause transient shock and myocardial impairment. This crisis may add to the development of the apical ballooning syndrome. 

An AMI may contribute to LV apical wall motion abnormalities by the same pathophysiologic processes described in the stunned myocardium.  In AMI, however, high serum cardiac enzyme levels are observed following the development of the myocardial offense.  

Lastly, hypertrophic cardiomyopathy is another possible cause of LV hypokinesis with ballooning of the apex.  The asymmetrical myocardial hypertrophy, myofibrillar disarray, dynamic ventricular outflow obstruction and the decreased left ventricular compliance13 all contribute to the development of left ventricular wall motion abnormalities and apical ballooning.  Although the precise cause of these abnormalities in this setting is unknown, acute myocardial ischemia may be a likely triggering factor in the manifestation of the phenomenon.  Cases demonstrating a transient enlargement of the LV in patients with hypertrophic cardiomyopathy and normal coronary arteries have been reported.13-15

Based on the patient’s reported symptoms, ECG abnormalities, considerable anteroapical wall motion abnormalities, absence of obstructive epicardial coronary artery disease, and her remarkable recovery, the most probable clinical scenario is that an acute ischemic insult produced a transient contractile dysfunction leading to a regional bulging (ballooning) of the myocardium.   The observed ECG abnormalities (symmetrical T-wave inversion with QT prolongation, and ST elevation on inferior and lateral wall leads) have been associated with LV stunning and other ischemic syndromes.16  In this patient’s clinical setting, the ECG changes suggest the absence of acute myocardial infarction even though small ST-segment elevations were noted.  Silent electrocardiographic infarcts have been described in both right ventricular infarcts and in patients with prior infarcts.  However, the ECG portrayed here is not in favor of acute infarction.  Furthermore, the enzyme data reinforce these observations.  For an AMI to produce pervasive segmental wall-motion dyskinesis, as in the case of transmural infarcts, enzyme leakage from the injured myocardium would have to yield extremely elevated serum enzyme levels.  The possibility that coronary vasospasm (either due to transient, altered adrenergic activity, or to an embolus) led to infarction with subsequent spontaneous reperfusion, would again demonstrate very high peaks of cardiac enzymes.17, 18  It is also unlikely that emboli alone would have simultaneously occurred in both segments of the right and left coronary arteries producing the features described in our patient.

Thus, given the clinical presentation and the remarkable recovery of the left ventricular function after conservative treatment, stunning of the myocardium seems the most likely explanation for this patient’s clinical manifestations.

ACKNOWLEDGEMENT

Angiographic and cineangiographic pictures provided by Dr. A. Ameen.

REFERENCES

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