Clinical syndromes of stunned or hibernating myocardium

INTRODUCTION — Left ventricular (LV) dysfunction, which may be an important consequence of coronary artery disease, can result from acute myocardial ischemia or myocardial infarction [1,2]. In addition, two other clinical syndromes can be associated with LV dysfunction:

●Transient postischemic dysfunction, called "stunned" myocardium

●Chronic, but potentially reversible, ischemic dysfunction, called "hibernating" myocardium

In patients with the latter disorder, LV function may improve markedly and mortality may be reduced following successful coronary revascularization. The time course of recovery is variable.

The clinical syndromes associated with stunned and hibernating myocardium and the methods used to detect stunned myocardium will be reviewed here. The pathophysiology of these disorders and the diagnosis and treatment of hibernating myocardium are discussed separately. (See "Pathophysiology of stunned or hibernating myocardium" and "Evaluation of hibernating myocardium" and "Treatment of ischemic cardiomyopathy".)

CLINICAL SYNDROMES — Stunned myocardium follows an episode of acute coronary ischemia. In comparison, hibernating myocardium occurs in the clinical syndromes of unstable and chronic stable angina, left ventricular (LV) dysfunction, or heart failure (HF). Stunned myocardium and hibernating myocardium may also coexist in some patients. Research suggests that hibernating myocardium may occur from repetitive episodes of stunning [3].

Chronic coronary syndrome — Support for the role of stunned or hibernating myocardium in stable angina comes from several observations:

●In patients with coronary artery disease and chronic stable angina, prolonged, but reversible LV dysfunction (stunning) occurred after a symptom-limited dobutamine infusion despite normal myocardial blood flow and myocardial oxygen consumption [4]. The degree of stunning was related to the severity of the coronary stenosis and the reduction in peak myocardial blood flow.

●LV dysfunction at rest in some patients with chronic stable angina improves after revascularization with coronary artery bypass graft surgery (CABG) or percutaneous transluminal coronary angioplasty (PTCA) [5-12]. In one PTCA study, for example, 59 of 81 (73 percent) hypokinetic or akinetic segments improved after revascularization [12]. With multivariate analysis, the best predictor of improvement in resting LV ejection fraction (LVEF) after CABG was the number of viable, asynergic myocardial segments per patient demonstrated on a resting thallium perfusion scan, that is, the number of segments that were hibernating; there was no correlation with the degree of angina [5].

Myocardial recovery may also be related to the degree of ischemia. One study using quantitative thallium-201 imaging after exercise and with redistribution, showed that improvement was more likely in regions with persistent defects with a 25 to 50 percent reduction in thallium uptake compared to regions with persistent defects in which thallium uptake was reduced by >50 percent (59 versus 21 percent) [13].

The reinjection of a second smaller dose of thallium immediately following the redistribution images improves the detection of stress defect reversibility [14]. This method can identify viable territories in as many as 50 to 70 percent of regions that were deemed scar by the standard three- to four-hour redistribution protocols [15-17]. The positive and negative predictive values for improvement in perfusion and wall motion are in the range of 85 percent with this technique, significantly higher than those of redistribution imaging alone. (See "Assessment of myocardial viability by nuclear imaging in coronary heart disease".)

An equally accurate method for establishing hibernation is dobutamine echocardiography, which examines the inotropic or contractile reserve of dysfunctional but viable myocardium. Viable myocardium shows improved regional contractile function (inotropic reserve), as assessed by simultaneous transthoracic echocardiography, and increased metabolic activity in response to low dose dobutamine [18]. (See "Dobutamine stress echocardiography in the evaluation of hibernating myocardium" and "Evaluation of hibernating myocardium".)

Acute coronary syndromes

Unstable angina — Unstable angina encompasses a variety of clinical conditions, including new onset chest pain, progressive effort angina, rest angina, and post-myocardial infarction (MI) angina. (See "Acute coronary syndrome: Terminology and classification".)

As described below, severe myocardial ischemia or infarction produces regional wall motion abnormalities on echocardiography or perfusion defects on perfusion imaging. Studies in which coronary occlusion occurred during percutaneous coronary intervention have shown that regional wall motion abnormalities on echocardiography occur within 10 to 30 seconds, before the onset of electrocardiographic abnormalities or chest pain (figure 1) [19-21].

Among patients with unstable angina, the time course of myocardial recovery after the cessation of chest pain is variable, ranging from less than two hours in patients with a short duration of chest pain (≤10 minutes) to more than 24 hours in patients with prolonged angina [22,23]. This delay in recovery, which occurs in the absence of recurrent chest pain, is thought to reflect myocardial stunning [22,24].

Hibernating myocardium also may be present, as patients with unstable angina who have not had a previous MI may have persistent reductions in perfusion and wall motion at rest [23]. Abnormal preoperative regional wall motion function is reversible with CABG in 40 percent of these patients; this improvement in wall motion is associated with an improvement of global LV function [25]. In one series, patients with unstable angina and abnormal preoperative LV function at rest had a 5- and 10-year survival after CABG that was not significantly different from that of patients with normal preoperative LV function [26].

Hibernating myocardium appears to be more common in unstable than stable angina (75 versus 28 percent in one series) [27]. The greater frequency of hibernating myocardium may explain why the 10-year survival after CABG in this study was significantly higher in patients with unstable angina and preoperative LV dysfunction than in those with stable angina and preoperative LV dysfunction; in comparison, survival in unstable and stable angina was equivalent among patients who had normal preoperative LV function.

Acute myocardial infarction — Most patients who present with an ST segment elevation MI (STEMI) who are treated with reperfusion therapy have significant stunning with subsequent improvement in myocardial function [28,29]. This was illustrated in the US HEART study, which evaluated 249 patients with anterior STEMI in whom sequential echocardiograms were obtained [28]. At 90 days, 22 percent of those with abnormal LV function and wall motion abnormalities had complete recovery and an additional 36 percent had partial recovery; most of the improvement occurred by day 14, consistent with the concept of myocardial stunning.

Myocardial hibernation in patients with MI can occur both in the area of infarction and in a region of the LV wall at a distance from the site of infarction [26]. Support for this hypothesis comes from a report of 15 patients with single vessel coronary artery disease who were asymptomatic after an STEMI and had no clinical or exercise-induced evidence of ischemia with thallium imaging; the patients were randomly assigned to either PTCA or conservative medical therapy [30]. After a two-month follow-up, patients who underwent PTCA had improvements in coronary blood flow as measured with a Doppler flow wire, the thallium-201 pathologic/normal ratio after exercise, LV wall motion, and LVEF; the patients randomized to medical therapy showed either smaller or no changes in these parameters. These data clearly demonstrate the occurrence of hibernating myocardium in the infarcted area or in an area that was presumed to be infarcted.

Hibernating myocardium after MI is associated with a high incidence of subsequent cardiac events. One report evaluated 158 patients with an MI, 57 percent of whom had hibernating myocardium as demonstrated by increased 18-fluorodeoxyglucose (FDG) uptake [31]. After a 23-month follow-up, a cardiac event (cardiac death, nonfatal MI, unstable angina, or late revascularization) occurred much more frequently in patients with evidence of hibernation (33 versus 3 percent). An increase in FDG uptake was the most significant predictor of a subsequent cardiac event, followed by the number of diseased vessels.

Severe left ventricular dysfunction or heart failure — The importance of hibernating myocardium has been evaluated in patients with ischemic cardiomyopathy and those referred for cardiac transplantation. The prevalence of hibernating myocardium was evaluated in a meta-analysis of 24 viability studies involving 3088 patients with coronary artery disease and LV dysfunction who had a mean LVEF of 32 percent [32]. Viability was documented in 42 percent of patients. (See "Treatment of ischemic cardiomyopathy".)

In addition, it has been estimated that more than 10 percent of patients referred for consideration of cardiac transplantation have an element of hibernating myocardium contributing to severe LV dysfunction [33-35]. As an example, one study of 112 cardiac transplant recipients found that severe coronary disease was found in all patients with a pretransplant diagnosis of ischemic cardiomyopathy (57 percent of the total population); it was also present in 24 percent of patients with a pretransplant diagnosis of idiopathic dilated cardiomyopathy [35].

Patients with multivessel coronary artery disease, LV dysfunction, no angina, and the lack of inducible ischemia by stress testing may also derive benefit by surgical revascularization if hibernating myocardium is present [36].

The decline in LV function that occurs with hibernating myocardium is associated with LV remodeling as manifested by increases in LV end-systolic and end-diastolic volumes and a more spherical shape of the LV [37,38]. Revascularization leads to partial reversal of these abnormalities (reverse remodeling) and an increase in LVEF [37]. The degree of improvement is significantly correlated with the number of segments that recover function after revascularization [37].

The possible benefit of revascularization with CABG or percutaneous coronary intervention in patients with coronary artery disease, LV dysfunction, and areas of hibernating myocardium is discussed separately. (See "Treatment of ischemic cardiomyopathy".)

NOVEL INSIGHTS — In many patients, chronic left ventricular (LV) dysfunction is related to a combination of hibernation, repetitive stunning, and both resting and stress-inducible ischemia. All these factors affect the likelihood of LV functional recovery. The following factors were shown to be important factors affecting success of revascularization in the PAAR-2 trial [39]:

●Extent of LV scar

●LV remodeling

●Ratio of the extent of viability versus scar

There are, however, no cut-off values for the extent of myocardial viability that is needed to result in LV functional recovery after revascularization. In addition, stabilization of LV ejection fraction (LVEF) after revascularization ("no improvement") can also be associated with improved outcomes [40]. It has also been recognized that improvement of LV function is not the only benefit of revascularization, but also improvement in diastolic dysfunction, prevention of ventricular arrhythmias, reduction in LV remodeling (dilatation, predominantly reduction in LV end-diastolic volume, but also reduction in LV end-systolic volume), and acute heart failure events may contribute to better outcomes after revascularization.

Conversely, it has been reported that when hibernation exists for longer periods of time, transition to LV fibrosis may occur, and revascularization can no longer improve LV function.

Lastly, myocardial scar but not ischemia was associated with ventricular arrythmias, appropriate implantable cardioverter-defibrillator shocks, and sudden cardiac death in patients with LVEF ≤35 percent [41].

UNCOMMON CAUSES — Isolated case reports suggest that myocardial stunning may also occur following tachycardia-induced cardiomyopathy, use of cardiotoxic chemotherapy, severe hypoxia, and status epilepticus [42-45].

DETECTION OF STUNNED MYOCARDIUM — In the setting of one of the clinical syndromes described above, noninvasive evaluation can detect myocardial stunning, although such imaging modalities are not routinely used for this purpose in clinical practice.

Echocardiography — Myocardial ischemia produces regional wall motion abnormalities that can be detected by echocardiography within 10 to 30 seconds of acute coronary artery occlusion [19,20]. These changes occur prior to the onset of electrocardiographic changes or the development of symptoms (figure 1).

The time course of recovery after the cessation of chest pain is variable, ranging from less than two hours in patients with a short duration of chest pain (≤10 minutes) to more than 24 hours in patients with prolonged angina [22]. This delay in recovery, which occurs in the absence of recurrent chest pain, appears to reflect myocardial stunning [22,24]. (See "Role of echocardiography in acute myocardial infarction", section on 'Indications for echocardiography in MI'.)

Myocardial contrast echocardiography — Myocardial contrast echocardiography (MCE) utilizes intravenous infusion of microbubbles, which have a distinct ultrasonic density from blood or tissue and which can traverse the microvasculature, permitting visualization of myocardial perfusion. By providing simultaneous left ventricular (LV) function and perfusion information via a single modality, MCE can effectively identify dysfunctional but perfused myocardium [46].

Dysfunctional segments of the LV following an ischemic insult may represent either infarcted or "stunned" tissue. Stunned myocardium has homogeneous myocardial contrast on MCE, representing normal blood flow with an intact microvasculature, implying that reperfusion occurred prior to necrosis. In this setting, systolic function is likely to return over the next several weeks [47-49]. (See "Contrast echocardiography: Clinical applications".)

DETECTION OF HIBERNATING MYOCARDIUM — The methods used to detect hibernating myocardium are discussed separately. (See "Evaluation of hibernating myocardium".)

SUMMARY

●Stunned myocardium – "Stunned" myocardium is characterized as transient post-ischemic dysfunction. Stunned myocardium occurs following an episode of acute ischemia. Routine use of noninvasive tests to detect stunned myocardium is not indicated. (See 'Clinical syndromes' above and 'Detection of stunned myocardium' above.)

●Hibernating myocardium – "Hibernating" myocardium is characterized as chronic, but potentially reversible, ischemic dysfunction. Hibernating myocardium may be seen in patients with unstable and chronic stable angina, left ventricular dysfunction, and/or heart failure. (See 'Detection of hibernating myocardium' above.)

•Both stunned and hibernating myocardium may recover function after improvement in the ischemic insult.

•Left ventricular function often improves following revascularization in patients with hibernating myocardium.

ACKNOWLEDGMENT — The UpToDate editorial staff thank Dr. David Shavelle for his past contributions to prior versions of this topic review.