Chapter 16 Heart Disease (2024)

CASE?

What situations led to G. S.’s angina symptoms? What other activities besides shoveling snow should G. S. avoid?

ALERT!

The dyes that are commonly used during cardiac catheterizations can lead to serious side effects, such as anaphylactic reactions, drug interactions, and kidney failure, especially among patients sensitive to iodine-containing agents.

PRACTICE POINT

When used for cardiac catheterization, adenosine is dosed as a 140-mcg/kg/min infusion over 6 minutes, while regadenoson is given as a single 0.4-mg dose via intravenous (IV) push.

CASE?

G. S.’s doctor would like to investigate his symptoms further. What noninvasive test can be used to help differentiate true ischemic heart disease from other conditions with similar symptoms?

Lifestyle Modifications

Though some risk factors for the development of ischemic heart disease cannot be changed or avoided, such as male sex, family history, and genetics, there are a number of lifestyle modifications that can reduce the risk of cardiovascular events. Perhaps of the highest importance is the control of underlying conditions that increase cardiovascular risk, including hypertension and hyperlipidemia. Refer to Chapters 14 and 17, respectively, for discussions of these conditions and their treatment. Cigarette smoking is another important modifiable risk factor. Smoke exposure, both first and second hand, causes decreases in oxygen supply via vasoconstriction and increases in oxygen demand as the heart pumps against higher blood pressure. If a patient can quit smoking, cardiovascular risk falls significantly within 5 years of quitting.2 Finally, obesity significantly increases cardiovascular risks. Clinicians frequently recommend calorie-restricted diets and physical activity to bring patients down to normal weight.

Beta Antagonists

The most commonly used agents in the treatment of ischemic heart disease are the beta antagonists (beta blockers), especially in patients who have more than one episode of chest pain per day. As discussed in Chapter 15, these medications block the ability of the catecholamines to cause increases in heart rate, contractility, and blood pressure. The resulting decreased oxygen demand helps restore oxygen balance, reducing the risk of angina attacks. In addition to decreasing the risk of developing angina, beta blockers have additional benefits in patients with coronary artery disease, such as blood pressure reduction, cutting the risk of heart attack, and protecting against arrhythmias.

Of the four subgroups of beta antagonists, the cardioselective agents are typically the drugs of choice in the treatment of angina. By selectively inhibiting the beta₁ receptor, side effects, such as sexual dysfunction, hyperglycemia, and bronchospasm that are common with nonselective agents, can be minimized. Though certain side effects are reduced, the cardioselective beta blockers still have a number of troublesome effects. Bradycardia, dizziness, hypotension, and decreased exercise tolerance are common reactions that warrant a slow titration of these medications. For a complete discussion of the various beta antagonists and their typical dosing, refer to Chapter 15.

Calcium Channel Blockers

Calcium channel blockers, also discussed in Chapter 15, can improve the symptoms of ischemic heart disease by both decreasing oxygen demand and increasing supply. The dihydropyridines (eg, amlodipine, nifedipine) act primarily on the vasculature, causing vasodilation that can improve coronary blood flow and allow the heart to pump against lower levels of systemic vascular resistance. The nondihydropyridines (eg, diltiazem, verapamil), on the other hand, target the heart and cause a reduction in contractility and heart rate. Like the beta blockers, normalizing the oxygen balance improves chest pain and reduces the likelihood of future episodes of angina. Unlike the beta blockers, however, the calcium channel blockers may not have as many additional cardiovascular benefits. For this reason, the beta blockers remain the first-line therapy in ischemic heart disease. For patients with contraindications to beta blocker therapy or those who develop significant side effects, however, calcium channel blockers are appropriate alternatives. One exception to this rule is in patients who experience angina that is related to vasospasm. Studies have shown that calcium channel blockers are among the most efficacious medications in the treatment of this form of angina and should be used as first-line therapy in these cases.

Clinicians choosing between the two types of calcium channel blockers must take individual patient characteristics into consideration. For patients with concurrent atrial fibrillation or rapid heart rates, the mechanism of action of the nondihydropyridines may give added benefits beyond regulation of oxygen balance. For those patients with slow heart rates or heart failure, the dihydropyridines may be better agents. Regardless of the agent chosen, side effects must be closely monitored, with the nondihydropyridines likely to cause constipation and bradycardia, the dihydropyridines causing tachycardia and edema, and both groups likely to cause hypotension and dizziness. Chapter 15 contains an in-depth review of the calcium channel blockers, including agent names, dosing, and interactions.

Nitrates

Nitric oxide is a substance produced by the body that causes vasodilation. This effect can be mimicked with the administration of nitrates, medications that are broken down into nitric oxide–like compounds that cause a direct vasodilation. In ischemic heart disease, the vasodilation throughout the body produced by nitrates decreases oxygen demand of the heart while increasing oxygen supply by dilating coronary arteries. Many of the adverse effects experienced by patients taking nitrates are directly related to their mechanism of action. Headache, orthostatic hypotension, and reflex tachycardia are the most common side effects. In addition to the setting of acute ischemic heart disease, nitrates can be used alone to treat infrequent, predictable angina or in addition to beta blockers or calcium channel blockers to reduce the risk of future attacks.

For patients with acute chest pain, the most rapid-acting and widely used treatment is sublingual nitroglycerin (Nitro-Stat). Patients are typically instructed to place one nitroglycerin tablet (most often 0.4 mg) under the tongue at the onset of chest pain. Another dose may be administered every 5 minutes if the chest pain persists, up to a maximum of three tablets. Nearly 90% of patients with ischemic heart disease will have resolution of the acute symptoms with proper administration of nitroglycerin. If the symptoms are not relieved after two doses, the patient should seek immediate medical attention for the possibility of an acute coronary syndrome. In addition to the sublingual tablets, a number of other formulations of nitroglycerin are available. The lingual spray (Nitrolingual) is an alternative to the sublingual tablets in the treatment of acute angina attacks. It has a longer shelf life but higher cost. Intravenous (IV) nitroglycerin is available for use in a hospital setting.

A number of nitrate medications are available for prophylaxis of ischemic heart disease symptoms, with a goal of reducing the number of angina attacks that patients experience. Nitroglycerin is available in a transdermal patch formulation (Minitran, Nitro-Dur) that can be applied once daily. Nitroglycerin ointment (Nitro-Bid) and oral capsules (Nitro-Time) can also be used for long-term prophylaxis of angina but are rarely used due to difficulty of administration, sometimes requiring as many as four doses per day.

Isosorbide mononitrate (Monoket) and dinitrate (Isordil) are oral nitrate therapies that are used solely for prophylaxis. These agents are available in sustained-release formulations that have longer half-lives and require dosing only one to three times daily. Refer to Medication Table 16-2 for available products and dosage forms.

Other Treatments

A number of other important therapies are initiated in patients with ischemic heart disease that will be discussed in later sections of this chapter. Aspirin or clopidogrel are antiplatelet therapies that have been proven to reduce mortality and the risk of heart attack and stroke. If a patient has an elevated cholesterol level or is otherwise at high risk of heart attack or stroke, treatment with statin medications (discussed in Chapter 17) is indicated, and the angiotensin-converting enzyme (ACE) inhibitors (Chapter 15) are another class of medications with proven benefit for reducing mortality in patients with coronary artery disease.

For patients with advanced disease, physicians may decide to aggressively treat coronary artery disease with revascularization procedures to restore blood flow to an area of the heart with a blocked vessel. In percutaneous coronary intervention (PCI), a stent (small tube) is inserted into blocked arteries. Coronary artery bypass grafting (CABG) is the attachment of arteries from the patient’s arms or legs to the heart to allow blood to flow around blockages.

CASE?

Upon her arrival to the emergency department, V. O.’s blood sample has high levels of troponin and her EKG shows evidence of abnormal conduction. What type of acute coronary syndrome is V. O. likely having?

Nonpharmacological Treatment

It has been established that the best way to restore circulation to occluded (blocked) vessels is to perform PCI or CABG. PCI is usually the preferred therapy for patients with coronary artery disease that is less extensive and contained to areas that can be reopened with stents. CABG, on the other hand, is reserved for the most severe cases of coronary artery disease, as the procedure is much more invasive and carries higher risks.

Glycoprotein IIB/IIIA Inhibitors

In both STEMI and NSTEMI patients who undergo PCI revascularization, glycoprotein IIB/IIIA (GP IIB/IIIA) inhibitors are important medications that lower the risk of occlusion of stents and the need to have additional PCI procedures. Agents in this class of medications, including abciximab (ReoPro), eptifibatide (Integrilin), and tirofiban (Aggrastat), are administered intravenously and bind to a receptor that is responsible for platelet adhesion, or the ability of platelets to stick together. With the function of platelets reduced, patients are less likely to develop blood clots that re-occlude stented vessels. Because they decrease platelet function, the major side effect of these agents is unwanted bleeding, especially when they are combined with other agents that interfere with platelet function or the body’s ability to form clots. If a patient has received fibrinolytic therapy (medication to dissolve blood clots, described next), has active bleeding, or has low numbers of platelets, these agents should be avoided. Dosing of GP IIB/IIIA inhibitors is based on a patient’s weight. See Medication Table 16-3 for dosing and adjustment information.

Fibrinolytics

In some areas, access to life-saving PCI and CABG is limited. In these cases, patients with STEMI may receive fibrinolytic therapy to help restore blood supply to the heart. These IV agents, including alteplase (Activase), reteplase (Retavase), and tenecteplase (TNKase), bind to fibrin, an important component of blood clots. Once bound, the fibrinolytics begin to break down the clot and open the occluded coronary artery. Because of their mechanism of action, the fibrinolytics will dissolve clots throughout the body, not only those present in coronary arteries. For this reason, these agents should not be used in patients with active bleeding, a history of hemorrhagic stroke, extremely high blood pressure (higher than 180/110 mm Hg), or recent internal bleeding, among other contraindications. Finally, the use of fibrinolytics is also controversial in patients older than 75 years of age. Some studies suggest that patients treated may have higher mortality rates when compared to those who did not receive these agents. The dosing regimens for fibrinolytic therapies are complex and are listed in Medication Table 16-3.

Unfractionated and Low Molecular Weight Heparins

Unfractionated heparin and the low molecular weight heparins, enoxaparin (Lovenox) and dalteparin (Fragmin), are important anticoagulant medications that are typically administered in the early stages of an acute coronary syndrome. Unlike GP IIB/IIIA inhibitors, aspirin, and clopidogrel, which work on platelet function, these anticoagulants interfere with the body’s clotting cascade to inhibit clot formation. For a full discussion of their mechanism of action and dosing, refer to Chapter 27. Regardless of whether the patient has suffered a STEMI or NSTEMI, undergoing PCI or fibrinolytic therapy, heparins are typically administered for the first 24–48 hours of hospitalization to decrease the risk of additional clot formation. Like other agents that affect the body’s ability to form blood clots, these agents must be used cautiously in patients who have active bleeding, are taking other medications that interfere with the body’s clotting ability, or have a high risk of developing a bleed.

Other Treatments

In addition to these important early treatments for STEMI and NSTEMI, a number of other supportive measures are also initiated. For some patients with oxygen saturation less than 90%, intranasal oxygen should be started. Nitroglycerin and morphine can be used together to control chest pain. Other therapies that are often started in the early treatment phase of an acute coronary syndrome, such as aspirin, beta blockers, and clopidogrel, are continued into the long-term treatment phase and are discussed below.

ALERT!

Unfractionated heparin carries an additional risk of causing heparin-induced thrombocytopenia (HIT), an immune reaction that destroys the body’s own platelets. If a patient has a history of this reaction, both heparin and low molecular weight heparins should be avoided, though the latter class of agents is associated with a much lower risk of causing this reaction.

Beta Antagonists

Beta antagonists are typically initiated via the IV route in the early phase of treatment and later switched to an oral formulation and continued indefinitely. After a myocardial infarction, beta blockers have a proven survival benefit, reduce the risk of having a second event, and prevent ventricular remodeling. Their antihypertensive effects also help to control another important cardiovascular risk factor, elevated blood pressure. Similar to the agents chosen to treat ischemic heart disease, the cardioselective beta antagonists are the most commonly used subgroup. Clinicians must carefully monitor the side effects of hypotension and bradycardia as they can induce additional ischemic events or stoke. To avoid these issues, the beta blockers are initiated at lower doses and slowly increased toward target levels.

Aspirin

Aspirin is another agent that is typically initiated in the early stages of an acute coronary syndrome, regardless of the type of event. The primary benefit of this agent is platelet inhibition. Within 10 minutes of administration, aspirin irreversibly binds to cyclooxygenase-1 (COX1), the enzyme responsible for the production of thromboxane A2, an important factor in platelet aggregation and adhesion. It is also theorized that aspirin’s anti-inflammatory effects may play a role in risk reduction. With platelet function diminished and the immune system tempered, the risk of forming additional clots, occluding a stent, and having future cardiovascular events is reduced. Like other antiplatelet therapies, the major side effect of aspirin therapy is a risk of bleeding, particularly of the gastrointestinal tract. To help reduce this risk, the lowest effective dose of aspirin is used. In the early phase of treatment, an initial 162-mg dose is administered followed by 81 mg daily, thereafter.

Platelet Aggregation Inhibitors

Another type of antiplatelet therapy that may be considered in acute coronary syndrome are the platelet aggregation inhibitors. These agents (clopidogrel, prasugrel, and ticagrelor) inhibit platelet function by binding to receptors that normally play a role in platelet aggregation. For patients who have undergone PCI with stenting, they can help to prevent stent occlusion. Depending on the type of stent inserted, patients may be treated with platelet aggregation inhibitors daily for several months up to an indefinite period of time. Clopidogrel is also used as an alternative to aspirin in patients with contraindications to its use. Because of bleeding risk, clopidogrel and prasugrel are not administered to patients who may require CABG. If CABG is needed in patients who have received this medication, a 5-day wash-out period must pass before the procedure can be performed. (This appears to be less of an issue with ticagrelor.) When these agents are used in combination with aspirin, bleeding risk is increased. To reduce this risk, only low-dose aspirin (100 mg or less) is usually used in combination with platelet aggregation inhibitors.

Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers

In the first 24 hours following a myocardial infarction, treatment with an oral angiotensin-converting enzyme (ACE) inhibitor is usually started and continued indefinitely. Many studies have shown improved survival and reduced re-infarctions when these agents are initiated in the early phase of treatment. The body releases angiotensin II and aldosterone after ischemic events in an attempt to maintain appropriate blood pressure. In the long term, however, these substances are actually harmful to the heart, increasing the rate and degree of cardiac remodeling. An ACE inhibitor can reduce the levels of these substances. If a patient exhibits symptoms of heart failure, which are discussed below, ACE inhibitor therapy has been shown to be even more beneficial. For patients with contraindications or side effects while on ACE inhibitor therapy, angiotensin II receptor blockers (ARBs) may be a good alternative option. The common side effects of ACE inhibitor and ARB therapy include elevations of potassium levels, decreases in kidney function, and low blood pressure. For a complete discussion of ACE inhibitor and ARB medications, refer to Chapter 15.

Statins

The statins are a group of medications used to reduce cholesterol levels in the blood. As described above, high levels of cholesterol increase a patient’s risk of developing atherosclerotic plaques and coronary artery disease. Statin therapy can reduce cholesterol levels significantly and, in turn, reduce the risk of cardiovascular disease. In patients with existing coronary artery disease or a myocardial infarction, it is theorized that statins have additional benefits, called pleiotropic effects, that go beyond their cholesterol-lowering effects. One hypothesis is that statins help to stabilize plaques, making unstable plaques less likely to rupture and cause future myocardial infarctions. The anti-inflammatory effects of statins may decrease cardiovascular risks, as well. For a full discussion of statins and other lipid-lowering medications, see Chapter 17.

CASE?

If B. R.’s symptoms are primarily lower-leg edema and cold extremities, what side of the heart is likely compromised?

Nonpharmacological Treatment

The body’s normal response to decreased stroke volume is to retain sodium and water. This harmful response to heart failure is made even worse if a patient consumes large quantities of salt in the diet. Most experts recommend a sodium restriction to less than 2 g each day. This lifestyle modification can significantly decrease the risk of heart failure exacerbations and reduce the doses of medicines needed to control the disease. It is also important for heart failure patients to remain active. Though overexertion can worsen heart function, mild to moderate exercise has been proven to be an important piece of many treatment regimens. Finally, clinicians focus heavily on improving patient adherence to the medication regimen. It has been shown that nonadherence is the most common cause of hospitalization for heart failure exacerbation. Educating patients about pillboxes, simplifying drug regimens, and reducing other barriers to adherence are of utmost importance.

Beta Antagonists

In the past, the beta antagonists were a class of medications avoided in patients with heart failure. It was not until a number of recent trials showed a significant improvement in patient mortality and decreases in hospitalizations for heart failure that these agents became routinely used components of heart failure treatment regimens. It is theorized that the benefit of beta blockers lies in their ability to stop the effects of catecholamines on the heart, decrease oxygen demand, or stop ventricular remodeling. Because of their tendency to reduce contractility and cause heart failure symptoms, however, these agents are only started in patients with stable heart failure and at very low doses. Dose increases are performed in 2-week intervals and monitored closely. If a patient experiences worsening heart failure, the dose is immediately reduced to previously tolerated levels and only increased after another 2-week interval has passed.

Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers

The ACE inhibitors are considered the cornerstone of heart failure treatment. By inhibiting the renin-angiotensin-aldosterone system, these medications have numerous benefits. Preload is reduced when aldosterone release is inhibited, afterload is decreased when angiotensin II production declines, and ventricular remodeling can be halted or reversed. Studies have shown that the ACE inhibitors not only reduce the risk of heart failure exacerbations, but they also improve survival. For those patients who develop a cough due to ACE inhibitor exposure, the ARBs can be substituted. Though they are not as well studied as the ACE inhibitors, these medications do have some evidence to support their use. The ARB valsartan may be used in combination with sacubitril, a neprilysin inhibitor, to further reduce the risk of death in patients with heart failure (Medication Table 16-4).

Hydralazine and Isosorbide Dinitrate

Before renin-angiotensin-aldosterone system–mediating medications were widely available, another combination of vasodilators was commonly used to treat heart failure. Studies predating the ACE inhibitors and ARBs shed light on the favorable effects of the combination of hydralazine (Apresoline) and isosorbide dinitrate (Isordil) on both mortality and hospitalizations due to worsening heart failure. Hydralazine is a potent direct arterial vasodilator that reduces afterload, while the isosorbide dilates veins and reduces preload. Today, ACE inhibitors and ARBs are first- and second-line agents with considerably better efficacy and safety evidence. However, for some populations, especially African Americans, the combination of hydralazine and isosorbide dinitrate can still be an important treatment option. Though both agents are available generically, a name brand combination tablet (BiDil) is available combining 37.5 mg of hydralazine and 20 mg of isosorbide dinitrate, dosed one to two tablets three times daily. Despite their efficacy in select patients, side effects still limit the overall use of this combination. Headaches, rebound tachycardia, and the potential to cause drug-induced lupus require close monitoring.

Aldosterone Antagonists

Another group of medications that have proven risk reduction and mortality benefits is the aldosterone antagonists. Though these agents fall under the class of potassium-sparing diuretics, it is their antialdosterone effects that are responsible for their benefit in heart failure. As described in Chapter 14, aldosterone causes retention of water and sodium, increasing preload initially, but worsening symptoms of pulmonary and lower-extremity edema in the long term. Aldosterone may also have a direct effect on heart tissue, increasing the rate of ventricular remodeling. Spironolactone (Aldactone) has been studied extensively in heart failure and shows the greatest benefit in patients with severe heart failure. Eplerenone (Inspra) is an alternative in male patients who experience spironolactone-induced gynecomastia (painful breast enlargement).

Diuretics

Accumulating fluid and edema are a constant concern for heart failure patients. To help treat these symptoms, patients are usually prescribed a diuretic. Though these medications have no mortality benefit, they are used to improve quality of life. Thiazide diuretics are considered too weak to adequately control edema related to heart failure. For this reason, loop diuretics, including bumetanide (Bumex), furosemide (Lasix), and torsemide (Demadex) are the drugs of choice. Close attention must be paid to ensure proper dosing, as over-diuresis may be harmful. Clinicians often instruct patients to use their body weight as a guide for diuretic dosing, increasing the dose if weight increases and vice versa.

Digoxin

Digoxin (Lanoxin) comes from a class of medications known as the cardiac glycosides. In the past, it was theorized that the main benefit of adding this medication was a positive inotropic effect, meaning an increase in contractility. Today, it is thought that low doses of digoxin actually improve heart failure symptoms by blocking a number of the harmful proteins and hormones that cause ventricular remodeling. This agent is available in two doses, 0.125 mg and 0.25 mg, is available generically, and is dosed once daily. Over the years, a number of conflicting studies caused debate about whether digoxin should be used in heart failure, at all. The evidence suggests that digoxin may reduce heart failure symptoms and the risk for hospitalization, but it does not improve survival. Experts generally agree that the lack of a mortality benefit and serious side effects such as nausea, dizziness, bradycardia, or other arrhythmias make this drug difficult to use. What was once a first-line therapy for heart failure has now become the last-line agent, only used when all other treatments are maximized and a patient is still having exacerbations.

Diuretics

To help reduce pulmonary and lower-extremity edema, high doses of diuretics are started upon hospital admission. IV loop diuretic therapy is usually initiated. If the loop diuretic is not sufficient on its own to improve symptoms, a thiazide-like diuretic, such as metolazone, can be added for a synergistic effect. When the acute exacerbation has resolved, the patient can be returned to oral loop diuretics.

Positive Inotropes

The positive inotropes are medications that increase heart contractility. These agents are used temporarily to boost stroke volume until the exacerbation can be controlled. One mechanism by which this action is accomplished is by activation of cardiac beta₁ receptors. Dobutamine, an IV synthetic catecholamine, is the most commonly used beta₁ agonist in the treatment of acute exacerbations of heart failure. This agent is relatively selective for the beta₁ receptors, leading to minimal side effects through alpha₁ and beta₂ activation. Doses are typically started at 2.5–5 mcg/kg/min and slowly increased to a maximum of 20 mcg/kg/min.

Another mechanism by which contractility is increased is inhibition of an enzyme called phosphodiesterase III (PDE3). Under normal conditions, this enzyme plays a role in regulating calcium concentration in heart cells. When it is inhibited, calcium levels rise and contractility is increased. The effect, however, is not limited to cardiac tissue. PDE3 inhibition in the vasculature causes vasodilation and reductions in preload and afterload, effects that contribute to improved stroke volume. Milrinone is the most commonly used PDE3 inhibitor. It is dosed intravenously at a rate of 0.5 mcg/kg/min but must be adjusted if patients have renal failure. Because it does not act on beta receptors, patients on beta blocker therapy will not have a reduction in effect, but side effects such as hypotension, arrhythmias, and headache are still a possibility.

Regardless of which positive inotrope is chosen, two important factors must be considered. With long-term use, both of these medications, and others with similar mechanisms of action, cause an increase in mortality. They must be used for the shortest time possible, and, when they are discontinued, it must be done carefully to avoid a return of heart failure symptoms. The doses must be slowly decreased to ensure the patient can tolerate their withdrawal.

Vasodilators

In acutely ill heart failure patients, fluid retention causes large increases in preload and afterload. Clinicians use potent IV vasodilators to return these factors to normal levels. They are categorized by their predominant effect: arterial or venous vasodilation.

Nitroglycerin in its IV formulation is an important heart failure treatment. It acts primarily on the venous side of the vasculature, with only minimal dilation of arteries. Preload reductions with a subsequent improvement in pulmonary edema are its main benefit. Doses of 0.5–3 mcg/kg/min are administered via continuous infusion, starting at the lower end of the range and titrated upward to effect and tolerability. The most commonly reported side effects in this setting are headache and hypotension due to excessive vasodilation. As seen when it is used in ischemic heart disease, tolerance to these effects may develop when nitroglycerin is used for extended periods.

Nitroprusside (Nitropress) is a mixed vasodilator, affecting both the arterial and venous systems. It causes dilation by increasing production of nitric oxide, one of the body’s natural vasodilators. The result is a decrease in both preload and afterload. Doses of 0.5–3 mcg/kg/min are administered as continuous infusions starting at lower doses that are increased every 5–10 minutes. Beside the expected side effects of hypotension, dizziness, and headache, nitroprusside has a unique adverse event: cyanide and thiocyanate toxicity. High levels of cyanide affect the body’s ability to transport oxygen, leading to confusion, weakness, and syncope (feeling faint or passing out). Though this effect is rare at typical doses, patients with kidney failure are at higher risk.

Atrial Fibrillation

Atrial fibrillation is characterized by rapidly beating atria. It is thought that this abnormal heartbeat occurs when an extra pathway opens to allow depolarization to reenter the atria and restart an unneeded contraction. If this dysfunction occurs, the atria will contract at a rate of 400–600 beats per minute, well above the normal rate of 60–100 beats per minute. Though this is extremely fast, many patients have no symptoms and can be in atrial fibrillation for years before a clinician discovers it. The lack of symptoms is due to regulation by the AV node, the gateway to the ventricles. When it is functioning properly, the AV node will not allow all of the 400–600 depolarizations to be transmitted to the lower half of the heart. If this ability is lost, however, patients will often begin to complain of “skipped heartbeats” or palpitations. When clinicians listen to the patient’s heart with a stethoscope, they will discover an irregularly irregular heartbeat as the atria and ventricles beat out of sync.

EKG tracings performed on patients with atrial fibrillation will display one major difference when compared to a normal EKG. In these cases, the typical P wave is replaced with many jagged, erratic waves or no P wave, at all. For an example of an EKG tracing of atrial fibrillation, see Figure 16-4.

The consequences of atrial fibrillation can vary greatly. Some patients may have the condition for many years and not develop serious complications. In other cases, however, the outcome may be the onset of heart failure, atrial enlargement, or, the most worrisome result, a stroke. When the atria beat at a very high rate, blood cannot be pumped effectively. If it is allowed to pool, clots will begin to form in the atrium. A dislodged blood clot may travel to the brain and cause a stroke, an event that happens in 5% to 7% of atrial fibrillation patients each year.4 To reduce this risk, these patients are often started on warfarin (Coumadin), dabigatran (Pradaxa), rivaroxaban (Xarelto), apixaban (Eliquis), or edoxaban (Savaysa). These medications interfere with the production of important clotting factors, inhibiting the formation of a clot. For a full discussion of these agents and the clotting cascade, refer to Chapters 26 and 27.

Ventricular Tachycardia and Fibrillation

Often the result of ischemic damage to the heart after an acute coronary syndrome, ventricular tachycardia and fibrillation are very dangerous rhythms with dire consequences. Ventricular tachycardia is defined as heartbeats originating in the ventricle that occur at a rate faster than 100 beats per minute. When large areas of the heart die, the electrical system can become badly damaged. This leads to the formation of reentry pathways in the ventricles that allow depolarization to occur chaotically along abnormal routes. The result is a rapidly beating ventricle, unguided by the timely depolarization of the SA node. In contrast to atrial fibrillation, fast heart rates in the ventricle are considered life threatening, as blood cannot be pumped to the body effectively.

If it is allowed to progress, ventricular tachycardia may lead to ventricular fibrillation, or complete disarray of the electrical system of the heart. This lethal condition is the cause of death in 50% of myocardial infarctions. When the ventricle is in fibrillation, no coherent heartbeats occur, only minor quivering of the chamber. Unless it is rapidly treated, all blood flow stops and the risk of death is extremely high.

EKG tracings of ventricular tachycardia and fibrillation lose all resemblance to the normal EKG tracing discussed above, due to the extreme disarray of the electrical system of the heart. In ventricular tachycardia, the disorganized, rapid contraction of the ventricles appears as a series of repetitive narrow or wide spikes, completely lacking P waves, QRS complexes, or T waves. If this condition progresses to ventricular fibrillation, this repetitive pattern is lost to a chaotic, jagged tracing that mirrors the quivering of the fibrillating ventricle. See Figures 16-5 and 16-6 for examples of ventricular tachycardia and fibrillation tracings.

Torsades de Pointes

Torsades de pointes is translated to mean twisting of the points, a description of what this arrhythmia looks like on an EKG (as seen in Figure 16-7). Like ventricular fibrillation, torsades de pointes is a life-threatening abnormal heartbeat. It arises during the phase of rest after each depolarization, called the refractory period, when electrical conduction is limited. In normally functioning hearts, this resting phase is in place to help avoid having a new contraction begin before the heart has fully recovered from the previous one. After this period is over, repolarization is complete and the heart cells are ready for another contraction. Certain medical conditions, electrolyte imbalances, genetic defects, or medications can delay repolarization. This weakens the ability of the myocardial cells in the refractory period to ward off early contractions. If a new wave of depolarization happens during this weakened refractory period, the patient can develop torsades. Clinicians monitor the chance for developing torsades by examining the section of an EKG called the QT interval. If this segment of the tracing is prolonged, there is an increased risk of developing this life-threatening arrhythmia. Much like ventricular fibrillation, torsades causes an ineffective heartbeat, leading to impaired circulation of blood. If left untreated, death is a very common result. For a list of the common medications that can cause or contribute to torsades, see Table 16-1.

Bradyarrhythmias

In addition to rapid heart rates, arrhythmias can also come in the form of abnormally slow heartbeats. Called bradyarrhythmias, these slowed rhythms come in many types and range from the common sinus bradycardia, a slow heartbeat seen in athletes, to troubling AV blocks and escape rhythms. AV block is the result of a malfunctioning AV node. Though the atria contract normally, the wave of depolarization occasionally is not transmitted past the AV node, meaning the ventricles miss a beat. In its mildest form, no treatment is necessary, but symptoms can develop as the dropped beats become more frequent.

Escape rhythms are the heart’s way of replacing a damaged pacemaker. If the SA node is unable to perform its functions, the responsibility of initiating each heartbeat falls to the surrounding atrial tissue. When this happens, however, the heart rate is slightly slower. If the atrial tissue is also damaged, the responsibility falls to the AV node and the resting heart rate is even slower. If even the AV node cannot fulfill the duties of the pacemaker, the ventricular tissue itself can depolarize spontaneously, though the rate is as low as 30 beats per minute.

Nonpharmacological Treatment

Depending on the arrhythmia, clinicians can choose among a wide variety of nonpharmacological interventions. When acute arrhythmias threaten a patient’s life, the treatment of choice is often direct current cardioversion, using electrical current to reset the heart’s conduction system. As made famous by numerous medical dramas, patients are sedated, paddles are placed on the chest, and electrical current is applied to the heart. For patients suffering from severe bradyarrhythmias, pacemakers have become popular treatment options. These small devices, implanted into the pectoral (chest) area, are attached to electrodes embedded into the cardiac tissue. Sophisticated software can sense the patient’s heartbeat and take over if the physiologic electrical system can no longer perform its duties. Similar to pacemakers, implantable automatic cardioverter-defibrillators (ICDs) can be used in patients at risk of developing sudden cardiac death. Like the paddles used in acute treatment of arrhythmias, these devices can sense the onset of ventricular tachycardia or fibrillation and deliver an electrical shock to return the heart to a normal rhythm. Finally, ablation is a surgical procedure used to destroy abnormal conduction pathways that can be sources of arrhythmias. Using a special EKG, the exact location of the abnormal circuit can be discovered and destroyed using radio waves.

Type I Antiarrhythmics

The medications used to treat arrhythmias are divided into four general classes, depending on the electrolyte channels they affect. The type I agents primarily slow the transport of sodium into cardiac cells. Type II agents, the beta blockers, do not directly affect any electrolyte channels but reduce arrhythmic potential by blocking the effect of catecholamines on the SA and AV nodes. Type III agents block the influx of potassium into heart cells, and Type IV agents slow calcium transport.

The type I antiarrhythmic agents are further divided into three subgroups. The type Ia agents include quinidine, procainamide, and disopyramide (Norpace), and all are available generically. In addition to slowing the transport of sodium into cardiac cells, the type Ia agents also prolong the refractory period. As discussed with torsades de pointes, delaying this segment of the depolarization cycle actually increases the risk of developing arrhythmias. In addition to increasing the risk of the very condition they are attempting to treat, low success rates in the treatment of both ventricular and atrial arrhythmias limit the use of these agents significantly. Each agent in this class has unique side effects. Quinidine is notorious for causing severe gastrointestinal complaints, including vomiting, diarrhea, and abdominal cramping. Procainamide has been implicated as a cause of systemic lupus erythematosus, a serious immune disorder that can damage the skin, joints, kidneys, or other organs (see Chapter 14). Disopyramide causes dry mouth, blurry vision, constipation, and urinary retention, as it blocks cholinergic receptors.

The Type Ib agents include generic lidocaine (Xylocaine) and mexiletine (Mexitil) and cause a shortening of the refractory period while slowing sodium influx. These agents are used in the treatment of ventricular arrhythmias. Though it works well, IV lidocaine is limited to the treatment of ventricular arrhythmias in the hospital setting; there is no oral or injectable product suitable for outpatient use. Mexiletine, on the other hand, is available in a tablet formulation but is rarely used due to severe gastrointestinal side effects and poor efficacy.

Type Ic agents slow sodium transport into cardiac cells dramatically and have no impact on the refractory period. These agents, including flecainide and propafenone (Rythmol), are available as oral tablets and can be used to treat both atrial and ventricular arrhythmias. Though the refractory period is not shortened, their potent blockade of sodium transport causes an increased risk of arrhythmias via other mechanisms. Both of the type Ic agents are negative inotropes, meaning they decrease the contractility of the heart. For this reason, this subgroup of antiarrhythmic agents cannot be used in patients with heart failure.

Type II Antiarrhythmics

The type II antiarrhythmic agents are the beta antagonists. In addition to their other therapeutic actions; the beta antagonists can reduce the risk of developing both ventricular and atrial arrhythmias. In the ventricles, these medications block the potentially proarrhythmic (arrhythmia promoting) effects of catecholamines. In atrial arrhythmias, they block the AV node, decreasing the risk of transmitting unwanted contractions to the ventricles. For a full discussion of beta blockers, see Chapter 15.

Type III Antiarrhythmics

Though the use of most antiarrhythmics is limited by either severe side effects or an increased risk of developing arrhythmias, the type III agents are some of the most commonly used treatments. Medications in this subgroup, including amiodarone (Pacerone), dofetilide (Tikosyn), dronedarone (Multaq), ibutilide (Corvert), and sotalol (Betapace), act primarily by slowing the transport of potassium into cardiac cells, though some agents in the class have additional effects.

Amiodarone is available in an injectable dosage form as well as generic oral tablets and is one of the most effective treatments for ventricular and atrial arrhythmias. It has a mixed mechanism of action that borrows from many different classes of antiarrhythmics. The largest drawback with this agent is its numerous side effects. Patients can develop such varying reactions as dizziness, confusion, thyroid problems, eye problems, liver toxicity, bradycardia, or pulmonary fibrosis, a severe and sometimes fatal condition. Clinicians must carefully monitor all patients receiving amiodarone for the many potential side effects. In an effort to discover a safer drug with amiodarone’s efficacy, dronedarone was developed. It does lack many of the side effects of amiodarone but may increase mortality in patients with heart failure and is significantly less effective.

Sotalol’s mechanism of action includes both type II and type III properties. This injection or generic oral medication can be used to treat many arrhythmias, but its main use is in atrial fibrillation. Because of its beta blocker effects, patients must be monitored for low blood pressure, bradycardia, and other side effects of that class of medications. Perhaps more concerning, however, is the chance of prolonging the QT interval of the EKG and causing torsades de pointes. The risk is even higher if patients have kidney failure as this can lead to sotalol accumulation.

Dofetilide and ibutilide, oral and IV medications, respectively, are type III antiarrhythmic agents used to convert atrial fibrillation to a normal heart rhythm. Ibutilide and dofetilide are available as generic options. With either agent, clinicians must monitor patients’ electrolyte levels closely. If potassium or magnesium levels are low, there is a significant risk for developing torsades de pointes. To avoid this side effect, many experts recommend pretreating all patients with potassium and magnesium supplementation.

Type IV Antiarrhythmics

Calcium channel blockers, discussed at length as antihypertensives in Chapter 15, make up the type IV antiarrhythmic agents. In atrial fibrillation, these agents block the AV node, similar to the beta blockers. They may also play a role in decreasing the risk of developing ventricular arrhythmias caused by increased exertion or catecholamine release. In general, the nondihydropyridines are the agents of choice to treat arrhythmias, as they are more selective for the cardiac tissue. (See Medication Table 16-5.)

CASE?

From what type of shock is J. S. likely suffering?

Fluids

IV 0.9% sodium chloride, also known as normal saline, solution, lactated Ringer’s, or 5% dextrose solutions are collectively called the crystalloids. These fluids are usually the agents of choice to restore vascular volume because studies show they are as effective as other treatments but cause fewer side effects and are less costly. In some cases, clinicians turn to fluids called colloids, such as 5% albumin, hetastarch, or dextran. In theory, these solutions, which contain larger molecules than those found in crystalloids, should remain in the vasculature for longer periods of time before diffusing out into the tissues. In practice, however, studies comparing the crystalloids and colloids do not show a significant difference in survival, despite their theoretical advantages and higher cost.

Vasopressors

The most common intravenously administered vasopressors used to treat shock include dopamine, dobutamine, norepinephrine (Levophed), epinephrine (Adrenalin), and phenylephrine, all of which activate the receptors of the autonomic nervous system to cause vasoconstriction, increases in contractility, and increases in stroke volume. The use of vasopressors to increase blood pressure in patients experiencing shock requires close monitoring and careful dose titrations. A balance must be obtained that allows for extra vasoconstriction that supports blood pressure but not excessive constriction that cuts off blood supply entirely. This becomes especially difficult, as extremely high doses of these agents are often required to counteract the symptoms of shock. If patients are stabilized on a vasopressor regimen, care must also be exercised when trying to discontinue these medications. Abrupt withdrawal often results in sudden deterioration of symptoms, so patients are typically weaned off of vasopressors very slowly (see Medication Table 16-6).

ACE = angiotensin-converting enzyme; aPTT = activated partial thromboplastin time; IV = intravenous; SUBQ = subcutaneous.

ACE = angiotensin-converting enzyme; IV = intravenous.

AV = atrioventricular; IM = intramuscular; IV = intravenous.