Recurrent Ischemia and Recurrent Myocardial Infarction: Detection, Diagnosis, and Outcomes

Introduction

There has been a major decline in the incidence of myocardial infarction (MI) in the developed world, with the proportion of ST-elevation MI (STEMI) decreasing and the proportion of non–ST-elevation MI (NSTEMI) increasing (see Chapter 2 ). As survival following MI improves, more survivors are candidates for recurrent events, including recurrent MI. However, the incidence of recurrent MI in the community has fallen, with a similar magnitude as the decline in incident MI. In addition to improvements in secondary preventive pharmacotherapy, the shift toward invasive evaluation and management of the initial MI has contributed to this reduction in subsequent recurrent ischemic events. For example, in patients with STEMI, recurrent MI is less frequent after primary percutaneous coronary intervention (pPCI) (see Chapter 17 ) than after fibrinolysis, with in-hospital rates being approximately 2.0% versus 4.0%; readmission rates with recurrent MI at 1 year are approximately 4.8% and 9.6%, respectively.

Other changes in clinical practice have also affected the epidemiology of recurrent MI, with competing directions. MI event rates are sensitive to changes in MI definitions, and after the introduction of the Universal Definition of MI in 2000, the epidemiology of MI has continued to evolve (see Chapter 1 ). Moreover, the use of biomarkers with increased sensitivity (e.g., high-sensitivity troponin assays) have greatly increased the detection of MI (see Chapter 7 ). Increased use of revascularization will increase the incidence of periprocedural MIs. At the same time, the frequency of recurrent MI may be underestimated because patients dying from recurrent MI may be classified as experiencing sudden death.

Detection of Recurrent Ischemia and Infarction

Recurrent Ischemia Without Infarction

Recurrent ischemia after presentation with an acute coronary syndrome (ACS) portends an unfavorable outcome and has major implications for use of health care resources. Ischemic symptoms at rest carry a worse prognosis than ischemia with exercise. In the thrombolytic era, in the GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries) IIb fibrinolytic trial, recurrent ischemia occurred in approximately 23% of patients with STEMI and 35% of patients with NSTEMI.

Refractory ischemia, which was defined as symptoms of ischemia for 10 minutes with ST-segment deviation or definite T-wave inversion, and/or new hypotension, pulmonary edema, or cardiac murmur believed to represent myocardial ischemia (despite the use of nitrates and either β-blocker or calcium channel blockers), occurred in approximately 20% of patients with ischemia. Refractory ischemia was associated with an approximate doubling of 30-day mortality among patients with ST-segment elevation (11.8 % vs. 5.4%; P < .001) and an even greater mortality risk among patients without ST-segment elevation (12.0% vs. 2.7%; P < .001).

Most ischemia is silent, and can be detected on 24-hour continuous electrocardiographic (ECG) monitoring. The frequency and duration of silent ischemia has a direct relationship to prognosis. Several studies that used continuous ST-segment monitoring showed that 15% to 30% patients with NSTE-ACS had transient episodes of ST-segment changes. These patients had an increased risk of subsequent cardiac events, including cardiovascular death. ST monitoring has been shown to add independent prognostic information to the ECG, troponins, and other clinical variables.

In the MERLIN–TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non–ST-Elevation Acute Coronary Syndrome–TIMI 36) trial, continuous ECG recording was performed for 7 days in 6355 patients with NSTE-ACS; 42% of the patients underwent revascularization during the index hospitalization. Patients with ≥1 episode of ischemia (20%) during the first 7 days were at increased risk of cardiovascular death (7.7% vs. 2.7%; P < .001), MI (9.4% vs. 5.0%; P < .001), and clinically manifested ischemia (17.5% vs. 12.3%; P < .001) over the following year.

With early invasive evaluation and management of MI, the incidence of early recurrent ischemia has decreased substantially. Among patients with STEMI in the PAMI (Primary Angioplasty in Acute Myocardial Infarction) study, recurrent ischemia was significantly less frequent in patients who had reperfusion with pPCI (10.3%) than in those who received fibrinolytic therapy (28.0%). Similarly, a major effect of early invasive management for NSTEMI is the reduction in recurrent ischemic events (see Chapter 16 ).

Because of the adverse prognosis of recurrent ischemia, clinical practice incorporates the performance of serial ECGs, monitoring for recurrent ischemic symptoms, and in some centers, continuous ST-segment monitoring. Many STEMI and NSTEMI patients are discharged 3 to 4 days after they have undergone an invasive strategy with pPCI or a pharmacoinvasive strategy with stenting of the culprit and often nonculprit lesions, either at initial angiography or subsequently. In patients who have typical ischemic pain at rest, a stress test is not necessary to define the need for additional therapy. A test for inducible ischemia may be considered in patients who are not fully revascularized before hospital discharge to help determine whether coronary angiography should be performed and revascularization, as appropriate, should be undertaken (see Chapter 30 ).

Diagnosis of Recurrent Myocardial Infarction

Classification of Recurrent Myocardial Infarction

The criteria for the diagnosis of MI according to the Third Universal Definition of MI are discussed in Chapter 1 and shown in Table 1-2 . MIs are a heterogeneous group of events and are classified by the Universal Definition of MI into five types that differ according to pathophysiology, prognosis, and treatment (Table 1-4) . The diagnosis of the initial MI is discussed in Chapter 1 , Chapter 6 , and Chapter 7 . This section focuses on the diagnosis of recurrent MI as a complication in patients who have presented with an initial MI event.

Spontaneous Myocardial Infarction

Spontaneous MIs (type 1) are the most commonly observed MIs in clinical practice, and they are also the most common type of recurrent MI during the long-term. Clinical judgment is required to distinguish type 2 (supply–demand imbalance) MIs from type 1 MIs by taking into account the contribution of increased myocardial demand and decreased supply and the likely absence of acute plaque rupture based on all of the clinical information available (see Figure 1-3 ).

Myocardial Infarction Related to Percutaneous Coronary Intervention (Type 4a)

Myocardial necrosis associated with PCI is a frequent cause of early recurrent MI and may be caused by several mechanisms, including distal embolization of plaque and/or thrombus with resultant microvascular plugging, occlusion of a side branch or a major coronary artery, coronary dissection, spasm, or endothelial dysfunction. The association between type 4a MI and mortality is controversial and less important than spontaneous MI.

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