Myocardial Stunning and Hibernation

Etiology

Transient myocardial ischemia resulting from reduced coronary blood flow can lead to myocardial stunning, with the same underlying causes as CAD.

Pathophysiology

Cardiac myocyte death and tissue infarction occur when coronary blood flow is blocked or severely reduced for more than 20 to 40 minutes, potentially causing permanent loss of contractile function.[8] However, if coronary flow is only moderately reduced initially, myocardial contractility may be preserved for a longer period, and normal function can return upon reperfusion. In such cases, the chronically dysfunctional myocardium is termed "hibernating." Chronically dysfunctional myocardium in this context is termed "hibernating."[9] A stunned myocardium, on the other hand, requires an extended period to recover and regain contractility. Heyndrickx et al described a phenomenon in which a reversible period of ischemia in laboratory dogs induced prolonged regional dysfunction, known as "myocardial stunning."[10]

The underlying pathology of both myocardial stunning and hibernation is hypoperfusion. Notably, up to 40% of coronary stenosis does not impact maximum coronary flow. Maximum flow is reduced in arteries with 40% to 80% stenosis, but resting flow remains unaffected. However, stenosis exceeding 80% significantly reduces resting blood supply, dramatically impairing contractile capacity. Myocardial stunning and hibernation represent different degrees within the same clinical spectrum. Studies suggest that repetitive episodes of stunning due to episodic ischemia may eventually lead to myocardial hibernation.[11][12][13]

The key difference between stunning and hibernation lies in coronary flow. In stunning, resting coronary flow remains unaffected, whereas in hibernation, it decreases. Hibernation is characterized by postischemic dysfunction, which may be acute, subacute, or chronic, following one or more ischemic episodes. The outcome of myocardial hibernation depends on timely hemodynamic improvements, either through prompt revascularization or by reducing myocardial oxygen consumption before cellular death occurs.[14]

Several defense mechanisms, known as autoregulatory phenomena, are observed in response to reduced myocardial flow in the hibernating myocardium. These mechanisms include:

• When a sudden reduction in coronary flow occurs, the energy demands of the hypoperfused myocardium exceed the available supply, creating an imbalance that leads to a reduction in myocardial contractility and energy consumption. This results in a state of "perfusion-contraction matching."[15][16]

• At the cellular level, hibernating cardiac myocytes exhibit nucleolar condensation, which suggests apoptosis. This process alters the structure and protein composition of the heart and prompts structural remodeling to maintain functionality.[17][18][19]

• Coronary vasodilation occurs in response to decreased coronary flow, initially counteracting the drop in pressure as part of the autoregulatory response.

• A brief ischemic interval, known as myocardial ischemic preconditioning, protects the myocardium from the harmful effects of subsequent prolonged ischemia, especially when the ischemia is gradual rather than sudden.[20][21] The hypothesis suggests that reperfusion following the initial ischemic event provides protective benefits. This mechanism may explain how periodic ischemic episodes can precondition stunned myocardium, potentially reducing future ischemic damage.

• Cytostructural changes in hibernating myocardial segments include disorganization of contractile and cytoskeletal proteins, reduced mRNA expression, and a decrease in myocardial phosphates at the cytochemical level. These alterations reduce myofibril responsiveness to calcium and shift metabolism from oxidative to anaerobic processes, contributing to the dysfunction observed in hibernating myocardium.

• As inotropic reserve diminishes and resting flow decreases in hibernating myocardial segments, there is an increase in α-adrenergic receptors and a corresponding decrease in β-adrenergic receptors. These changes in receptor ratios reflect the myocardium's adaptive response to chronic ischemia, contributing to the altered contractile function observed in the hibernating myocardium.

History and Physical

Individuals with stunned or hibernating myocardium typically have a history of CAD or ischemic events, such as heart attacks. These patients often present with symptoms such as chest pain, shortness of breath, or fatigue, especially during exertion, due to impaired myocardial contractility. The severity and acuity of ischemia, along with other factors, can influence the presentation and variability of symptoms.

In the case of myocardial infarction, myocardial stunning often occurs after the infarction, particularly in patients who receive reperfusion therapy, with near-normal recovery observed within 2 weeks.[22][23] Myocardial hibernation has been observed not only in infarcted areas but also in regions adjacent to, yet remote from, the infarction. Post-reperfusion improvements in myocardial contractility have been demonstrated in these areas, as indicated by various parameters.[24]

Myocardial stunning or hibernation can also occur in chronic stable angina due to CAD. Left ventricular dysfunction often improves after revascularization, although the severity of angina does not always correlate directly with the number of hibernating regions involved.[25]

Unstable angina is characterized by repetitive episodes of chest pain, which may occur at rest, during exertion, or after a myocardial infarction. Myocardial ischemia can cause perfusion defects, which are detectable on echocardiography as wall motion abnormalities. Repeated episodes of myocardial stunning can eventually lead to myocardial hibernation over time. This process explains why hibernating myocardium is more commonly observed in unstable angina than in stable angina.[26]

A subset of patients with severe left ventricular dysfunction or heart failure may exhibit hibernating myocardium. In many of these cases, left ventricular remodeling is evident, with a spherical shape and increased volume seen on imaging. These parameters often improve after reperfusion, a process known as "reverse remodeling of the left ventricle," indicating recovery of some hibernating myocardial segments.[27]

Evaluation

The diagnosis of stunned or hibernating myocardium is made using appropriate diagnostic tests, which are essential for mapping viable myocardium and assessing contractile reserve. These tests should provide information on the potential for complete or partial restoration of left ventricular contractility and myocardial function if revascularization is performed promptly. Ideally, the tests should be sensitive and specific for identifying myocardial tissue, as well as noninvasive and widely available, contributing to positive outcomes and improving long-term patient survival.

Echocardiography

Echocardiography provides valuable information on myocardial viability. An end-diastolic wall thickness of 0.6 cm or less is considered indicative of limited potential for functional recovery.[28] This value indicates that the affected myocardium may not respond to revascularization.

Dobutamine Stress Echocardiography

DSE involves the use of transthoracic 2-dimensional echocardiography combined with low-dose dobutamine to noninvasively evaluate the contractile reserve of dysfunctional myocardium.[29] Dobutamine may be combined with atropine or, in some cases, nitroglycerin to increase myocardial blood flow.[30]

A biphasic response in DSE is characterized by an initial improvement in myocardial contractility (wall motion) at low doses of dobutamine, followed by a subsequent deterioration at higher doses. This phenomenon occurs due to distinct physiological mechanisms. At low doses (≤10 μg/kg/min), dobutamine improves contractility in ischemic yet viable myocardium by enhancing coronary blood flow and stimulating β-adrenergic receptors. However, at higher doses (≥20 μg/kg/min), the increased myocardial oxygen demand surpasses the supply, especially in the presence of significant coronary artery stenosis, leading to ischemia and worsening wall motion abnormalities.

Clinically, a biphasic response indicates the presence of viable myocardium with significant ischemia, often associated with hibernating myocardial tissue or regions with severe stenosis. This response is important as it suggests the potential for functional recovery following revascularization procedures, such as CABG or PCI.

A uniphasic response in DSE is characterized by the absence of improvement at any stage, indicating persistent wall motion abnormalities or progressive deterioration without initial enhancement. This response is linked to distinct physiological mechanisms—persistent wall motion abnormalities suggest a scarred myocardium with no viability, often seen in transmural infarction, while progressive worsening indicates severe ischemia without viable tissue. Clinically, a uniphasic response points to a nonviable myocardium, typically consisting of scar tissue, and suggests a low likelihood of functional recovery with revascularization.

Tissue Doppler Echocardiography

Tissue Doppler echocardiography utilizes strain rate imaging to estimate left ventricular viability. The sensitivity of this technique significantly improves when combined with DSE, which enhances its ability to assess myocardial function and viability.[31]

Doppler Assessment of Mitral Inflow Pattern

Doppler echocardiography of left ventricular diastolic function can offer valuable information about myocardial viability, particularly through the early diastolic deceleration time. A deceleration time greater than 150 milliseconds is considered a positive prognostic indicator for successful revascularization.

Radionuclide Myocardial Perfusion Imaging

Stress redistribution single-photon emission computed tomography (SPECT) and fluorodeoxyglucose-PET (FDG-PET) are valuable imaging techniques for assessing myocardial viability and perfusion. SPECT utilizes a radioactive tracer to evaluate blood flow and myocardial perfusion, identifying ischemic or infarcted regions. FDG-PET uses a radioactive glucose analog to detect areas of altered metabolic activity, distinguishing between viable and nonviable myocardium. Although these techniques are effective, DSE generally offers slightly better predictive value for myocardial viability.[32]

Cardiac Magnetic Resonance Imaging

Cardiac MRI uses gadolinium as a contrast agent to assess myocardial viability. The absence of contrast enhancement on MRI typically indicates viable myocardium, which is likely to respond favorably to revascularization.[33]

Myocardial Contrast Echocardiography

Myocardial contrast echocardiography (MCE) can detect stunned myocardium by revealing a homogeneous contrast pattern, which indicates normal blood flow and intact microcirculation. In addition to evaluating left ventricular contractility, MCE helps identify dysfunctional yet perfused myocardium.[34]

Endocardial Electromechanical Mapping

Endocardial electromechanical mapping is an emerging technique for diagnosing stunned myocardium. This technique measures the amplitude of endocardial electrical signals and correlates these findings with wall motion studies to identify areas of reversible ischemia.

Treatment / Management

Myocardial stunning typically does not require specific treatment. However, temporary use of inotropes is indicated if severe myocardial dysfunction occurs.[35](B3)

Nisoldipine, a calcium antagonist, has been recommended to enhance functional recovery of reperfused myocardium, but only when administered before an ischemic event.[36] Angiotensin-converting enzyme inhibitors, such as enalapril and captopril, have been used to improve the contractile function of stunned myocardium. Additionally, hydralazine, enalapril, and captopril can help mitigate reperfusion-induced myocardial dysfunction and improve myocardial contractility.[37] (B3)

The observation that antioxidant therapy reduces free radical generation and contractile dysfunction starting at the time of reperfusion supports the concept that myocardial stunning is a manifestation of reperfusion injury.[38] The treatment for hibernating myocardium involves reperfusion of the hypoperfused myocardial tissue. Hibernating myocardium often presents with abnormal wall motion, which can normalize after interventions such as nitrate or inotrope administration, postextrasystolic potentiation, percutaneous transluminal coronary angioplasty, or CABG.(B3)

Differential Diagnosis

The differential diagnoses of myocardial stunning or hibernation include the following cardiopulmonary conditions:

• Acute pericarditis
• Aortic dissection
• Aortic stenosis
• Herpes zoster
• Idiopathic pulmonary arterial hypertension
• Infective endocarditis
• Mitral valve prolapse
• Myocarditis
• Myopericarditis
• Pneumothorax
• Acute pulmonary embolism
• Respiratory pneumonia
• Unstable angina

Distinguishing conditions with similar clinical features to myocardial stunning and hibernation is crucial for accurate diagnosis and management. Proper identification guides treatment decisions, ensuring timely interventions such as revascularization and avoiding unnecessary procedures for nonischemic causes.

Prognosis

The prognosis of myocardial stunning or hibernation depends largely on the timing of revascularization and the extent of myocardial damage. Prompt reperfusion may lead to partial or complete restoration of myocardial function, resulting in favorable long-term outcomes. However, delayed revascularization increases the risk of irreversible myocardial damage, which can lead to persistent heart dysfunction. The presence of comorbidities, such as heart failure or diabetes, can further negatively affect the prognosis.

Complications

Complications associated with myocardial stunning and hibernation may include heart failure, arrhythmias, and chronic ischemic heart disease. Prolonged stunning or hibernation can lead to reduced cardiac output and worsening left ventricular dysfunction. Furthermore, recurrent ischemic events can exacerbate underlying myocardial damage, increasing the risk of complications such as cardiogenic shock or myocardial infarction.