Management Principles in Myocardial Infarction

Fibrinolysis

Administration of a fibrinolytic agent was the cornerstone of reperfusion therapy before the development of primary PCI, and still constitutes important therapy in settings where primary PCI is not available or not available expeditiously (see Chapter 14 ). The oldest fibrinolytic agents (streptokinase and urokinase) are still widely used in some parts of the world because of cost. Subsequent evolution of fibrinolytic therapy has aimed to improve ease and rapidity of administration, as well as the balance of fibrinolytic efficacy versus bleeding. In comparison to streptokinase, later generation fibrinolytics, including alteplase, reteplase, and tenecteplase, have amplified effects at the sites of thrombus formation (see Chapter 15 ).

Despite the similarities in the early mechanisms of STEMI and acute coronary syndromes (ACSs) without ST-elevation, and the key role of thrombosis in both, fibrinolysis failed to demonstrate benefit in early studies of the treatment of unstable angina. Because those studies included low-risk patients, some experts have questioned whether there could be a role for coronary administration of modern fibrinolytic agents in high-risk NSTEMI. Nevertheless, because of the absence of established benefit and a clear increased risk of serious bleeding, professional society guidelines do not recommend administration of fibrinolytic agents to patients with NSTEMI.

Pathways of Care: ST-Elevation Myocardial Infarction

Pathways of care for patients with STEMI are aimed at minimizing the duration of ischemia and triage of patients to the optimal environment for management of the complications of MI (see Chapter 5 ). Timely primary PCI is preferred whenever it is available and provided by experienced STEMI teams, and has become the dominant approach to reperfusion therapy in most countries ( Figure 13-4 ). Critical elements of pathways of care for STEMI include prompt recognition by the patient of the need to call emergency medical systems, rapid dispatch and arrival of emergency providers (<10 minutes), in-ambulance diagnosis of suspected STEMI, administration of analgesia and antithrombotic agents, rapid transfer to a PCI-capable center (<30 minutes), and mobilization for timely PCI ( Figure 13-5 ). Direct admission to the catheterization laboratory avoids the delays involved in emergency department evaluation. When prehospital transfers are prolonged because of distance from the PCI center, or traffic and adverse weather, the option of prehospital administration of fibrinolysis is needed (see Chapter 14 ). Even after apparently successful fibrinolysis, transfer to a PCI-capable center is needed to treat the underlying stenosis, to minimize risks of re-occlusion, and to consider revascularization of nonculprit coronary stenoses (see the section on Recurrent Ischemia and Chapter 14 ).

Pathways of Care: Non–ST-Elevation Myocardial Infarction

The clinical presentation of NSTEMI is more insidious than that of STEMI and may be preceded by new-onset exertional angina, deteriorating or unstable angina, or no previous symptoms. Unlike STEMI, autonomic features do not usually accompany the onset of NSTEMI. Because of the pattern of onset, the patient may misinterpret the symptoms as gastrointestinal or musculoskeletal in nature, and presentation is frequently to nonemergency medical services (primary care or internal medicine, or to nonemergency chest pain clinics). The diagnosis is based on the clinical syndrome plus ECG findings of ischemia, but without persistent ST-elevation (see Chapter 1 and Chapter 6 ) and sensitive biomarkers of necrosis (e.g., high-sensitivity troponin; see Chapter 7 ). However, the diagnosis can be challenging in the presence of minor nonspecific ECG abnormalities and biomarkers of necrosis that may be elevated by supply–demand imbalance (type 2 MI) or myocyte necrosis in the absence of coronary occlusion (e.g., in heart failure or pulmonary embolism). Particular care is needed to identify patients with evolving infarction but who do not have ST-elevation at the time of first presentation. Repeated ECG analysis or continuous ST monitoring is important for this reason. Once the diagnosis of NSTEMI is established, antithrombotic therapies should be initiated while consideration of invasive evaluation is undertaken (see the section on Initial Risk Assessment ).

Analgesics

Relief of pain is important, not only to relieve distress, but also to avoid the consequences of sympathetic simulation on the heart, including increases in afterload and arrhythmogenesis (see Chapter 28 ). Intravenous opioid analgesia is the most commonly used therapy and should be carefully titrated, and is often administered with antiemetics. For example, intravenous morphine sulfate at a dose of 2 to 8 mg repeated at intervals of 5 to 15 minutes has been recommended, until the pain is relieved or side effects (e.g., hypotension, depression of respiration, or severe vomiting) emerge. The reduction of anxiety with successful analgesia diminishes the patient’s restlessness and the activity of the autonomic nervous system, with a consequent reduction of the heart’s metabolic demands. Morphine may also provide favorable effects in patients with pulmonary edema caused by peripheral arterial and venous dilation, reduction of the work of breathing, and slowing of heart rate secondary to combined withdrawal of sympathetic tone and augmentation of vagal tone. Observational studies have identified an association between administration of morphine and adverse outcomes in patients with ACS; however, it is challenging to disentangle this observation from confounding by indication.

Nitrates

Nitrates are commonly given in acute MI, and they may relieve vasospasm and reduce pain. By virtue of their ability to enhance coronary blood flow by coronary vasodilation and to decrease ventricular preload by increasing venous capacitance, sublingual nitrates have been recommended for the initial treatment of patients with MI. At present, the only groups of patients with STEMI in whom sublingual nitroglycerin should not be given are those with suspected right ventricular infarction or marked hypotension (e.g., systolic pressure <90 mm Hg), especially if accompanied by bradycardia. The patient should be observed for improvement in symptoms or change in hemodynamics. Even small doses can produce sudden hypotension and bradycardia, a reaction that can usually be reversed with intravenous atropine. Long-acting oral nitrate preparations should be avoided in the early course of STEMI because of the frequently changing hemodynamic status of the patient. In patients with a prolonged period of waxing and waning chest pain, intravenous nitroglycerin may help to control symptoms and correct ischemia, but requires frequent monitoring of blood pressure. Initiation of a reperfusion strategy in patients with STEMI should not be delayed while assessing the patient’s response to sublingual or intravenous nitrates. Despite the strong pathobiological rationale, administration of nitrates has not been shown to improve clinical outcomes compared with placebo in patients with MI (see the section on Other Medical Therapies to Reduce Ischemia ).