14
Diseases of the Cardiovascular System
Peter B. Lockhart, DDS
Yee-Ping Sun, MD
Cardiovascular disease (CVD) is the leading cause of mortality in the world. In 2017, CVD caused an estimated 17.8 million deaths worldwide, representing ~32% of all deaths and 360 million disability-adjusted life years (DALYs) lost.1 These numbers have climbed steadily both in absolute numbers and relative proportion since 2010. While the global mortality rate from CVD has increased in the past 30 years, the rates of CVD death in high-income countries has decreased and therefore reflects a significant increase in CVD death in low- and middle-income countries. CVD now accounts for the most deaths in all low- and middle-income regions (except in Sub-Saharan Africa where it is the leading cause of death in those >45 years and causes four to five times as many deaths as in high-income countries.2 As of 2016, CVD remained the leading cause of death in the United States, accounting for ~840,000 deaths. The annual total cost of CVD in 2014–2015 was estimated at $351 billion. It is estimated that in 2019, ~1.1 million Americans will have suffered a new coronary event and ~800,000 will have had a new stroke. This amounts to a coronary event and stroke every 40 seconds. There has been an overall decrease in CVD deaths over the past 30 years in the United States, though gender, socioeconomic, and racial disparities do exist. In particular, it has been estimated that the avoidable CVD death rate in black people is nearly twice as high as in white people.3
CVD includes hypertension, coronary artery disease (CAD), valvular heart disease (VHD), congenital cardiovascular defects, congestive heart failure (CHF), congenital cardiovascular defects, heart valve disorders, venous thromboembolic disease, and stroke (Table 14‐1).3 Although these diseases are associated with a high mortality, the associated morbidity and detrimental effect on the quality of life of affected individuals are perhaps even more pronounced, since they affect nearly all populations. This chapter considers common cardiovascular conditions and their implications for the practice of dentistry.
What follows is an overview of the demographics, diagnosis, medical management, and dental management considerations for the more common cardiovascular conditions seen in dental offices.
Table 14‐1 Percentage breakdown of deaths attributable to cardiovascular disease in the United States in 2016.
Source: Adapted from Benjamin EJ, Muntner P, Alonso A, et al. Heart disease and stroke statistics—2019 update: a report from the American Heart Association. Circulation. 2019;139(10):e56–e528.
| Coronary heart disease | 43% |
| Stroke | 17% |
| Hypertension | 10% |
| Heart failure | 9% |
| Diseases of the arteries | 3% |
| Other | 18% |
GENERAL CONSIDERATIONS FOR THE DENTAL MANAGEMENT OF THE CARDIAC PATIENT
The high prevalence of cardiac disease in the general population suggests frequent dental management considerations in dental practice. Advances in cardiac surgery and medical management of patients with congenital heart disease (CHD), for example, have resulted in large numbers of adults with a variety of cardiac conditions that may be of concern with regard to stressful, prolonged, or invasive dental procedures. It is therefore important for dentists caring for these patients to understand their cardiac condition as well as medical history.
Multiple longstanding uncertainties and controversies exist concerning the dental management of patients with cardiovascular diseases and conditions. There are, however, multiple guidelines and scientific papers to help dental practitioners with assessment and management issues for specific cardiac patient populations.4 Additional studies are needed, however, as many of these guidelines are based on small studies and expert opinion.5 The lack of systematic reviews and formal guidelines does not release the dental healthcare provider from the responsibility to use good clinical judgment in accordance with the provider’s training, knowledge base, and experience.
Importance of the Medical History
The patient’s medical history should be documented in the patient’s chart. Important aspects of the medical history screening include (1) current medications; (2) history of chest pain, arrythmia, or cardiac surgery; (3) indications for antibiotic prophylaxis prior to dental procedures; and (4) primary care physician’s and/or cardiologist’s name and contact information. For many of these patients, consultation with their primary care physician or cardiologist may be desirable for questions concerning elements in the patient’s history that are unclear, the severity of active problems, and potential risks from invasive or stressful dental procedures.
The medical history for patients with cardiac disease or conditions may reveal other medical problems of importance. For example, diabetes mellitus has a direct impact on the progression of CAD and therefore increases the risk of invasive or stressful procedures.6 The finding of uncontrolled hypertension is of particular concern for patients undergoing dental procedures, and protocols have been proposed to evaluate these patients and carry out dental procedures in the safest manner.7
Oral healthcare providers should be aware of medications they prescribe that may have systemic side effects and interact with the patient’s medications (e.g., analgesics with anticoagulant properties). Likewise, some cardiovascular medications have side effects that may cause intraoral changes (e.g., oral dryness, gingival overgrowth). Other cardiac medications may have significant implications for dental procedures (e.g., anticoagulants, both antiplatelet therapy and vitamin K antagonists).
Some aspects of dental management are generic to several of the patient populations in this chapter.8 For example, acquiring blood pressures (BPs) has become standard in many dental practices and it is particularly important for cardiac populations. Additionally, the determination of vital signs prior to dental procedures is an important preventive measure. There is a high prevalence of hypertension in the general population and therefore in dental practices. Although hypertensive crises are extremely rare in the dental office setting, the increased risks associated with painful or stressful procedures support the practice of taking a BP on all new patients and those with significant cardiovascular disease. Many patients will not be aware that they have hypertension and it is important that they be referred to their primary care physician for evaluation.
Given the nature of this patient population, it is desirable for oral healthcare professionals treating patients with cardiovascular disease to be certified in American Heart Association (AHA) basic life support or advanced cardiac life support.9
Importance of Preventive Dentistry
Although there may be a weak association between periodontal disease and atherosclerosis, independent of known risk factors (e.g., smoking), a causal link has not been established. Nevertheless, pain and stress from an acute pulpitis or abscess could potentially trigger angina, stroke, or myocardial infarction (MI). Poor oral hygiene is associated with more frequent bacteremia from routine daily activities (e.g., tooth brushing) and this clearly puts some cardiac patients at risk for infective endocarditis.10,11
Stress
An overriding focus for dental care is to reduce the risks from long, painful, or stressful dental procedures that increase catecholamine release and induce hemodynamic changes before, during, and following a procedure, to include increased heart rate and BP, and decreased myocardial output. Examples include patients with a history of hypertension, coronary artery bypass grafts (CABG), coronary stents, arrhythmia, and some cardiac medications. Studies have reported that the sound of a dental handpiece alone is enough to increase stress and anxiety.12 Multiple short appointments may be preferable and premedication with antianxiety agents is commonly used for this purpose. Nitrous oxide/oxygen analgesia can be used for most cardiac patients, though given the mild negative inotropic effect, use in patients with severe left ventricular dysfunction or pulmonary hypertension should be avoided.
Use of Vasoconstrictors for Dental Procedures
Risks from local anesthetics containing epinephrine as a vasoconstrictor are controversial and may be of concern with some cardiac conditions.13 The benefits of vasoconstrictors (e.g., hemostasis and more profound and prolonged anesthetic effect) likely outweigh the risk of systemic effects from stress-related endogenous epinephrine (e.g., increased heart rate and BP).14 In the vast majority of stable outpatients with cardiovascular disease, local anesthetics with epinephrine can be used safely. In patients with a very recent MI (within the past month) or history of ventricular arrhythmias (particularly Brugada syndrome if using procaine), it would be reasonable to consult with the patient’s cardiologist.15,16
Concentrations of epinephrine greater than 1:100,000 are felt to be unnecessary and may carry a higher risk.17 Clearly, it is important to restrict the total volume of local anesthetics, and especially epinephrine. A small dose of low-concentration epinephrine should not have a significant systemic effect.14 When using epinephrine, it is important to aspirate, but due to the small diameter of dental anesthetic needles, a negative aspiration does not insure that intravascular injection will not occur.
Nonsteroidal Anti-inflammatory Drugs
Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective oral analgesics and anti-inflammatory agents. Their use has been associated, however, with a small but significant increased risk of cardiovascular events. This association is present among all NSAIDs, including both traditional NSAIDs such as diclofenac, ibuprofen, and naproxen as well as selective cyclo-oxygenase-2 inhibitors such as celecoxib.18 The risk may be lower with ibuprofen (total daily dose <1200 mg/day) and naproxen (<500 mg/day). The risk appears to be related to duration and dose, though the increased risk can be seen with 8 days.18 In addition to the risk of cardiovascular events, it is also important to appreciate that use of NSAIDs in patients on antithrombotic medications, including aspirin, clopidogrel, and the direct oral anticoagulants, may also increase the risk of gastrointestinal bleeding.19 Based on these observations, it is generally recommended that in patients with existing cardiovascular disease, use of nonpharmacologic therapy and acetaminophen be prioritized. There is no adverse cardiovascular risk associated with use of acetaminophen and the hepatic risk is also extremely low provided the total daily dose is 3–4 g in the absence of significant alcohol intake. If acetaminophen use is not effective, risk–benefit assessment would favor a short course of NSAID use. In patients who are on multiple thrombotic agents, consultation with the treating cardiologist/internist will be important if use is expected to exceed 1 week.
Oral Manifestations of Cardiac Medications
Side effects from cardiac drugs may cause oral mucosal changes. For example, gingival overgrowth can occur with calcium-channel blockers and xerostomia often results from antihypertensive drugs. Altered taste (e.g., metallic) has also been reported with antihypertensives (e.g., an angiotensin-converting enzyme inhibitor, ACEi), and they may be associated with lichenoid reactions. If the side effects are severe enough, a change in antihypertensive medication may avoid the necessity for topical steroids.
HYPERTENSION
Definition, Classification, and Epidemiology
There has been wide variation in the definition of hypertension. The most recent guidelines put forth by the AHA, American College of Cardiology (ACC), and American Society of Hypertension define hypertension as a systolic BP >130 mm Hg or diastolic BP >80 mm Hg.20 This is in contrast to European Society of Cardiology (ESC) guidelines that have a higher threshold for hypertension definition, with a systolic BP >140 mm Hg or a diastolic BP >90 mm Hg (Table 14‐2).21 Regardless of the precise cut point for defining hypertension, it remains a significant cause of morbidity and mortality worldwide.
Hypertension is classified as primary and secondary. Primary or essential hypertension accounts for ~90%. The precise etiology of primary hypertension is complex and is likely multifactorial, with contributions from genetic factors, age, dietary intake (particularly sodium and potassium), physical inactivity, obesity, and alcohol use. In ~10% of cases, a specific treatable cause of hypertension can be identified; these entities are termed secondary hypertension. The most common causes of secondary hypertension include drug-related causes (in particular NSAIDs, oral contraceptives, and corticosteroids, to name a few), primary renal disease, obstructive sleep apnea, renovascular disease (such as fibromuscular dysplasia), and endocrinologic causes such as a primary hyperaldosteronism (see Table 14‐3).
The global prevalence of hypertension was estimated to be ~1.1 billion in 2015 and is estimated to reach 1.5 billion by 2025. From 2013–2016, it was estimated to be present in ~116 million Americans and in 2015, ~150 million across central and eastern Europe. Worldwide, it is estimated to be present in ~30–45% of adults. The high prevalence is consistent across low-, middle-, and high-income countries. The prevalence increases with age, with a prevalence of >60% in those >60 years. Around 35% of patients with hypertension are completely unaware of their diagnosis. The prevalence of hypertension among African Americans is among the highest in the world, with an age-adjusted prevalence of 57.6% in men and 53.2% in women between 2011 and 2016.20
Table 14‐2 Major guideline definitions for hypertension.
| SBP (mm Hg) | DBP (mm Hg) | ||
|---|---|---|---|
| ACC/AHA Guidelines | |||
| Normal | <120 | and | <80 |
| Elevated | 120–129 | and | <80 |
| Stage 1 Hypertension | 130–139 | or | 80–89 |
| Stage 2 Hypertension | ≥140 | or | ≥90 |
| ESC Guidelines | |||
| Optimal | <120 | and | <80 |
| Normal | 120–129 | and/or | 80–84 |
| High normal | 130–139 | and/or | 85–89 |
| Grade 1 hypertension | 140–159 | and/or | 90–99 |
| Grade 2 hypertension | 160–179 | and/or | 100–109 |
| Grade 3 hypertension | ≥180 | and/or | ≥110 |
| Isolated systolic hypertension | ≥140 | and | <90 |
ACC, American College of Cardiology; AHA, American Heart Association; DBP, diastolic blood pressure; ESC, European Society of Cardiology; SBP, systolic blood pressure.
Cardiovascular Risk Association
In 2015, hypertension was the leading global contributor to premature death, accounting for ~10 million deaths and over 200 million DALYs. In addition, despite advances in diagnosis and treatment, the DALYs attributable to hypertension have increased by 40% since 1990. Hypertension has a clear independent and continuous relationship with the incidence of stroke (both hemorrhagic and ischemic), MI, sudden cardiac death, heart failure, peripheral arterial disease, and renal disease. There is also increasing evidence linking hypertension with atrial fibrillation, as well as cognitive decline and dementia. Increases in both systolic and diastolic BP have been associated with adverse cardiovascular events, though elevated systolic BP is more predictive in older patients (>50 years) as opposed to elevated diastolic BP, which is more predictive in younger patients (<50 years). Many adult patients with hypertension have other CVD risk factors (see Table 14‐4). Among patients with hypertension in the United States in 2009–2012, 63% had hypercholesterolemia, 50% were obese, 27% had diabetes, 16% were current smokers, and 16% had chronic kidney disease (CKD).
Table 14‐3 Causes of secondary hypertension.
Medication-related
|
| Renal parenchymal disease |
Renovascular disease
|
| Obstructive sleep apnea |
Endocrinologic causes
|
| Aortic coarctation |
Diagnostic Evaluation
Diagnosis
Most patients with hypertension are asymptomatic and the sequelae of hypertension are typically seen years after sustained exposure. Because of this, early and accurate diagnosis is critical. BP assessment in the office setting is relatively easy, but often results in misleading assessments. To accurately assess BP in the office, careful attention needs to be paid to appropriate patient preparation, patient positioning, measurement technique, and documentation (see Table 14‐5). Before a diagnosis is made, multiple measurements should be taken, both at the same visit and averaged over several visits ideally. Since the ideal conditions for in-office measurement are often practically challenging, the use of ambulatory blood pressure monitoring (ABPM) can also be helpful. These monitors are typically programmed to obtain readings every 15–30 minutes throughout the day and every 15–60 minutes in the evening. Testing occurs over a 24-hour period and occurs while patients participate in their normal daily activities. ABPM is particularly helpful in identifying both white-coat hypertension (defined as hypertension in the office setting but no hypertension while at home) as well as masked hypertension (defined as no hypertension in the office but hypertension while at home). While data surrounding the impact of white-coat hypertension on CVD are conflicting (though the majority suggest no increased risk), the risk of masked hypertension is similar to that seen with sustained hypertension.
Table 14‐4 Cardiovascular risk factors common in patients with hypertension.
Source: Adapted from Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018;71(19):e127–e248.
| Modifiable Risk Factors | Relatively Fixed Risk Factors |
|---|---|
|
|
Table 14‐5 Appropriate steps to accurate in-office blood pressure (BP) measurements. Proper technique is key to an accurate BP assessment. Improper technique has been well demonstrated to lead to inaccurate BP measurements.
| Key Steps for Proper BP Measurements | Specific Instructions |
|---|---|
| Step 1: Properly prepare the patient |
|
| Step 2: Use proper technique for BP measurements |
|
| Step 3: Take the proper measurements needed for diagnosis and treatment of elevated BP/hypertension |
|
| Step 4: Properly document accurate BP readings |
|
| Step 5: Average the readings | Use an average of ≥ 2 readings obtained on ≥ 2 occasions to estimate the individual’s level of BP |
| Step 6: Provide BP readings to patient | Provide patients the SBP/DBP readings both verbally and in writing |
BP, blood pressure; DBP, diastolic blood pressure; SBP, systolic blood pressure.
Clinical Evaluation
The three main goals of the medical evaluation of patients with hypertension are to (1) identify treatable (secondary) or curable causes; (2) assess the impact of persistently elevated BP on target organs; and (3) estimate the patient’s overall risk profile for the development of CVD. A routine history and physical examination should be performed, though it is important to note that making a diagnosis of hypertension is beyond the scope of practice of dentistry. The history should focus on the duration of the hypertension and any prior treatment. Asking the patient about the duration of their high BP may be misleading, as in many cases the patient will not have had a BP measurement for many years prior to the discovery of hypertension. Symptoms of organ dysfunction, lifestyle habits, diet, and psychosocial factors should be included. The main goals of the physical examination are to accurately confirm the diagnosis of hypertension, identify signs of end-organ involvement, and evaluate potential causes of secondary hypertension (see Table 14-3). These types of examinations should only be performed by trained and experienced healthcare providers. Once the diagnosis of hypertension is made, it is recommended that patients undergo laboratory testing with measurement of fasting blood glucose, complete blood count, lipid prolife, serum creatinine, sodium, potassium, calcium, thyroid-stimulating hormone, and urinalysis.20 Electrocardiogram is also recommended and may show signs of left atrial enlargement, left axis deviation, and abnormalities suggestive of left ventricular hypertrophy. Cardiac arrhythmias such as atrial fibrillation may also be seen. Transthoracic echocardiography can be considered in patients with a diagnosis of hypertension. In addition to providing a more sensitive assessment of left ventricular hypertrophy (LVH) and left atrial dilation, it also provides information on left ventricular systolic and diastolic function, valvular function, estimates on pulmonary artery pressures, and can serve as a screening for the presence of aortic coarctation, another potential secondary cause of upper extremity hypertension. The identification of LVH is important as it is an independent predictor of mortality in patients with hypertension. Hypertrophy of the ventricle initially results in the impairment of left ventricular relaxation (diastolic function) and can ultimately progress to weakening of the myocardial pumping function (systolic dysfunction). Impairment in both diastolic and systolic function can result in clinical signs of CHF.
Management
Management should start with lifestyle modifications, including weight reduction, adoption of the DASH (Dietary Approaches to Stop Hypertension) diet, sodium restriction, increased potassium intake, regular physical activity, and reduction in or cessation of alcohol consumption (Table 14‐6). Careful attention should be paid to the patient’s current medication list during history-taking and concerted efforts should be made to reduce the use of potentially offending medications if clinically possible. Adoption of these changes can be challenging for patients practically. Importantly, even with 100% adherence to these changes, many patients will still require pharmacologic therapy.20
Table 14‐6 Nonpharmacologic management of hypertension.
Source: Adapted from Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018;71(19):e127–e248.
| Intervention | Recommendation | Approximate Decrease in SBP in Hypertensive Patients | |
|---|---|---|---|
| Weight loss | Weight/body fat | Best goal ideal body weight, but aim for 1 kg reduction for overweight adults. Expected about 1 mm Hg reduction for every 1 kg in weight loss | 5 mm Hg |
| Healthy diet | DASH dietary pattern | Consume diet rich in fruits, vegetables, whole grains, and low-fat dairy products with reduced content of saturated and total fat | 11 mm Hg |
| Reduced intake of dietary sodium | Dietary sodium | Optimal goal is <1500 mg/d, but aim for at least 1000 mg/d reduction | 5–6 mm Hg |
| Enhanced intake of dietary potassium | Dietary potassium | Goal 3500–5000 mg/dL, ideally through consumption of a diet rich in potassium | 4–5 mm Hg |
| Physical activity | Aerobic | 90–150 min/week | 5–8 mm Hg |
| Dynamic resistance | 90–150 min/week | 4 mm Hg | |
| Isometric resistance | 3 sessions/week | 5 mm Hg | |
| Moderation in alcohol intake | Alcohol consumption | Reduce alcohol intake (men ≤2, women ≤1 drink(s) daily) | 4 mm Hg |
DASH, Dietary Approaches to Stop Hypertension; SBP, systolic blood pressure
There are several classes of antihypertensive medications. The results of an increasing number of trials suggest that at the same level of BP control, most antihypertensive drugs provide similar degrees of cardiovascular protection. In those with uncomplicated hypertension, beginning with a low dose of a thiazide diuretic (e.g., 12.5–25 mg of hydrochlorothiazide or 25–50 mg of chlorthalidone) has the advantages of very low cost and low risk of metabolic complications such as hypokalemia, lipid abnormalities, and hyperuricemia. Use of an ACEi, angiotensin receptor blocker (ARB), or a calcium-channel blocker can also be considered as first-line agents. In patients whose BPs are markedly elevated at first diagnosis (systolic BP >20 mm Hg above target or diastolic BP >10 mm Hg), initiation of a two-drug approach is very reasonable. If the patient remains hypertensive on a thiazide diuretic, ACEi/ARB, and calcium-channel blocker, use of an aldosterone antagonist (such as spironolactone or eplerenone) or a beta-blocker, particularly one with some degree of alpha blockade (such as a carvedilol), can be added as second-line options. It is important to note that certain factors will affect clinical decision-making in the pharmacologic management of hypertension, including ischemic heart disease, heart failure, CKD, diabetes, atrial fibrillation, and race/ethnicity (Table 14‐7).20
The role of education and the importance of patient contact are paramount in successfully treating hypertension. Self-recorded measurements and ambulatory BP monitoring aid in the physician’s titration of medications and monitoring of the 24-hour duration of action of antihypertensive agents. The monitoring of BP by oral healthcare providers will therefore support the overall medical care of their hypertensive patients.
Dental Management Considerations for Patients with Hypertension
Patients with elevated BP are potentially at increased risk for adverse events in a dental office setting, particularly if their BP is poorly controlled or if there is target organ disease involvement (heart, brain, kidney, peripheral arteries).7 However, the absence of target organ disease does not mitigate a careful evaluation and treatment of patients within safe and appropriate parameters of care. The primary concern for these patients is precipitating a hypertensive crisis, stroke, or MI. Poor compliance with antihypertensive medications and diet is a common problem, and dentists can help by reinforcing the importance of following medical advice and guidelines (Tables 14-4 and 14-5). Dental management guidelines have been proposed based on the medical model for assessment, risk stratification, and treatment of patients with hypertension.22–24
Side effects of antihypertensive medications vary and can include orthostatic hypotension, synergistic activity with narcotics, and potassium depletion. Although safe limits for invasive dental procedures cannot be strictly defined, and they are largely based on an individual patient’s overall medical condition, there arc general guidelines depending on whether patients have prehypertension, stage one or stage two hypertension, and target organ disease (Table 14-2). Elective treatment should be avoided if the BP is significantly above the patient’s baseline or if it is >180 mm Hg systolic or >100 mm Hg diastolic. If patients have any symptoms potentially related to hypertension, such as chest pain, headache, or focal neurologic symptoms, elective procedures should be canceled. For patients who have an urgent dental problem, it may be desirable to remove the source (e.g., abscessed tooth) if the patient has mildly elevated BP, but if significantly elevated, oral pain and infection can usually be well managed pharmacologically until the BP is brought under control. Patients may have somewhat elevated BP from pain and/or anxiety and they may have some lowering of their BP after local anesthesia, but this is unpredictable.
Table 14‐7 Pharmacologic management of hypertension in specific patient groups.
| Antihypertensive Preference | |
|---|---|
| Ischemic heart disease |
|
| Heart failure with reduced ejection fraction |
|
| Chronic kidney disease |
|
| Diabetes |
|
| Atrial fibrillation |
|
| African American |
|
| Pregnant women or those contemplating pregnancy |
|
ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker.
CORONARY ARTERY DISEASE
Definition and Epidemiology
CAD accounts for approximately 30%–50% of all cases of CVD in the United States. Almost 7% of or ~18 million Americans >20 years of age have CAD (7.4% in males and 6.2% in females). In 2016, CAD-related mortality was ~360,000 individuals, with mortality directly due to an MI ~110,000. It is estimated that each year 730,000 Americans will have a new coronary attack, and 355,000 will have recurrent attacks. While CAD remains a major cause of morbidity and mortality, gains have been made, with a reduction in relative and absolute rates of CAD-related deaths by ~32% and 15%, respectively.3
Pathophysiology of Stable Coronary Artery Disease versus Acute Coronary Syndromes
CAD is characterized by progressive obstruction of the epicardial coronary arteries. Atherosclerosis is the pathophysiologic process responsible for the development of these obstructions and begins as a fatty streak in early adolescence. The lesions progress over decades and develop into frank atherosclerotic plaques. This plaque is characterized by disruption of the vascular endothelium, extracellular lipid accumulation, smooth muscle cell migration/proliferation, and inflammation.25 Atherosclerosis may affect any vascular bed, including the coronary, cerebral, renal, mesenteric, and peripheral vascular systems. In the coronary circulation, progressions in these plaques can result in two distinct clinical entities: stable CAD and an acute coronary syndrome (ACS). In stable CAD, there is gradual progression of plaque growth leading to arterial luminal obstruction over years. Clinically, this manifests as progressive exertional angina due to the mismatch in myocardial oxygen demand and supply with exertion. ACSs, in contrast, are the result of plaque instability. In ACS, the unstable plaque (either obstructive or nonobstructive) ruptures and acute thrombosis occurs, leading to an abrupt decrease in myocardial oxygen delivery. If blood flow is not restored (either spontaneously, pharmacologically, or mechanically), this can result in myocardial injury, termed a myocardial infarction.26 While these two entities are the clinical result of coronary atherosclerosis, their management differs greatly, thereby making the clinical distinction critical in practice.
Risk Factors
The development of coronary atherosclerosis is influenced by several risk factors, including dyslipidemia, systemic hypertension, diabetes, cigarette smoking, diet, physical activity, obesity, family history, and inflammation. The impact of each of these factors upon CAD risk, however, differs among different subgroups. For example, diabetes and a low high-density lipoprotein (HDL) cholesterol/total cholesterol ratio have a greater impact in women, cigarette smoking has more of an impact in men, and systolic BP and isolated systolic hypertension are major risk factors independent of age or sex. Risk factor assessment is useful as a guide to therapy for dyslipidemia, hypertension, and diabetes; multivariable prediction rules can be used to help estimate risks for subsequent coronary disease events. Current guidelines recommend using the 10-year risk of cardiovascular events as a basis for initiating risk factor–modifying therapy for lipid abnormalities.27 Based on the increased risk conferred by the various CAD risk factors, concepts of “normal” have continued to evolve from “usual” or “average” to more biologically optimal values associated with long-term freedom from disease. As a result, optimal BP, blood glucose, and lipid values have been continually revised downward in the past 20 years.
Lipids
The total cholesterol concentration in serum is a major and clear-cut risk factor for CAD. In the Multiple Risk Factor Intervention Trial (MRFIT) of more than 350,000 middle-aged American men, the risk of CAD progressively increased with higher values of serum total cholesterol.28 In addition to total cholesterol, data from the Framingham Heart Study demonstrated that HDL is strongly inversely associated with CAD risk, low-density lipoprotein (LDL) is strongly directly associated with CAD risk, and triglycerides are mildly associated with CAD risk.29 In the nearly 35 years since the initial observations in the MRFIT trial, it has become clear that there is a linear relationship between LDL reduction and adverse event reduction, such as for every 38 mg/dL reduction in LDL there is ~23% reduction in major cardiovascular events.30 In the highest-risk population of patients who have suffered multiple cardiac events already, dramatic LDL reductions to as low as 30 and 50 mg/dL have confirmed that this relatively linear relationship holds true even after very low LDL levels.31–33
Based on these studies, there has been a paradigm shift away from a single appropriate cut point for lipid therapy, toward tailoring therapy based on overall risk. The most recent guidelines have recommended assessing the overall cardiovascular risk using the Atherosclerotic Cardiovascular Disease (ASCVD) algorithm.27 In patients who have clinical atherosclerotic cardiovascular disease, including established CAD, stroke, or peripheral vascular disease, use of a high-intensity statin (atorvastatin 40–80 mg daily or rosuvastatin 20–40 mg daily) is recommended. Diabetes is considered an ASCVD equivalent and in those patients use of at least a moderate-intensity statin is strongly recommended. In those patients who have an elevated 10-year risk (>7.5%) of an ASCVD event as predicted by the ASCVD risk calculator, use of a high-intensity statin is recommended. For all others, if the LDL is >190 mg/dL, treatment with a high-intensity statin is recommended. For intermediate-risk patients (5–7.5% 10-year risk), treatment with a moderate-intensity statin is recommended. For low-risk patients (<5% risk), the therapy should be tailored through a shared decision-making process (Figure 14‐1).
Hypertension
As previously discussed, hypertension and LVH are well-established risk factors for CAD morbidity and mortality. In patients with established CAD, careful management of hypertension is key to preventing recurrent ischemic events.
Glucose Intolerance and Diabetes Mellitus
Insulin resistance, hyperinsulinemia, and glucose intolerance all appear to promote atherosclerosis. As diabetic individuals have a greater number of additional atherogenic risk factors (including hypertension, hypertriglyceridemia, increased cholesterol-to-HDL ratio, and elevated levels of plasma fibrinogen) than do nondiabetic individuals, the CAD risk for diabetic persons varies greatly with the severity of these risk factors. Overall, patients with diabetes are at ~2.6-fold increased risk for cardiovascular death than patients without diabetes.34 Thus, aggressive treatment of these additional risk factors may help reduce cardiovascular events in diabetic patients.
Cigarette Smoking
Cigarette smoking is an important and potentially reversible risk factor for CAD and CAD events such as MI. For both men and women, the risk increases with increasing tobacco consumption.35 For example, in one study the risk of MI was sixfold increased for women and threefold increased for men who smoked at least 20 cigarettes per day, compared to nonsmoking control patients.35
Lifestyle and Dietary Factors
Dietary factors such as a high-calorie, high-fat, and high-cholesterol diet contribute to the development of other risk factors, such as obesity, hyperlipidemia, and diabetes, which predispose to CAD. Red meat consumption too is associated with an increased risk of total, cardiovascular, and cancer mortality.36 Conversely, a diet that emphasizes fruit and vegetables, the increased intake of dietary fiber, and the so-called Mediterranean-style diet rich in olive oil and nuts are associated with a decreased risk of CAD.37,38 Weight gain and obesity directly worsen the major cardiovascular risk factors, whereas weight loss appears to improve them.39 Epidemiologic data indicate that the moderate intake of alcohol has a cardioprotective effect.40–42 Elevation of serum HDL levels appears to be the primary mechanism by which alcohol imparts this benefit. It should be stressed that the benefits of alcohol apply only to moderate consumption and are not seen in those who “abuse” alcohol. Furthermore, the protective effects of alcohol do not apply to the risk of hemorrhagic stroke, death due to trauma, or cancer, all of which may be increased in individuals who consume greater amounts of alcohol.
Figure 14‐1 Atherosclerotic Cardiovascular Disease (ASCVD) management algorithm. Current guidelines recommend lipid management based on the presence (secondary prevention) or absence (primary prevention) of clinical ASCVD. (a) In patients with clinical ASCVD, moderate- or high-intensity statin is recommended. Addition of ezetimibe or a PCSK9 inhibitor can be considered in very high-risk patients. (b) In patients without clinical ASCVD, current guidelines recommend assessment of 10-year cardiovascular risk in those 40–75 years old and lifetime risk in those 20–39 years old using the ASCVD risk calculator. In patients with LDL >190 mg/dL, high-intensity statin therapy is recommended. In those with diabetes, moderate-intensity statin is recommended. If neither of these is present, consideration for therapy should be based on the 10-year risk as identified by the ASCVD risk calculator with inclusion of risk enhancers. If the risk decision remains uncertain, coronary artery calcium scoring can be considered. CHD, congenital heart disease; CRP, C-reactive protein; HDL, high-density lipoprotein; LDL, low-density lipoprotein; PCSK9, proprotein convertase subtilisin/kexin type 9; RCT, randomized control trial.
Exercise
Even a moderate degree of exercise appears to have a protective effect against CAD.43 In one study of middle-aged men, participation in moderately vigorous physical activity was associated with a 23% lower risk of death than that associated with a less active lifestyle, and this improvement in survival was equivalent and additive to other lifestyle measures such as smoking cessation, hypertension control, and weight control.44 Mechanisms that could account for the benefits of exercise include elevated serum HDL cholesterol levels, reduced BP, weight loss, and a lower incidence of insulin resistance.
Obesity
As already stated, obesity is associated with the development of several risk factors for CAD, including systemic hypertension, impaired glucose metabolism, insulin resistance, hypertriglyceridemia, reduced HDL cholesterol, and elevated fibrinogen. Data from the Framingham Heart Study, the Nurses’ Health Study, and other studies have shown the risk of developing CAD that is associated with obesity.45–47 The distribution of body fat appears to be an important determinant, as patients with abdominal (central) obesity are at greatest risk for subsequent CAD.48 Patients with central obesity, elevated levels of serum triglycerides, and (to a lesser degree) LDL cholesterol, low HDL cholesterol, insulin resistance, and hypertension are classified as having atherogenic dyslipidemia (metabolic syndrome).49 This syndrome is more difficult to treat and is associated with a worse prognosis than is an isolated increased LDL level.
Inflammation and Endothelial Dysfunction
Endothelial dysfunction appears to be an early step in the atherosclerotic process and may result from dyslipidemia, hypertension, and diabetes. Recent studies have suggested that coronary artery endothelial dysfunction predicts the long-term progression of atherosclerosis and an increased incidence of cardiovascular events. C-reactive protein (CRP) is an inflammatory biomarker that has been shown to be predictive of cardiovascular events. The JUPITER study has demonstrated that in apparently healthy persons without hyperlipidemia but with elevated CRP levels, rosuvastatin reduced the incidence of major cardiovascular events independent of the LDL-lowering impact.50 The benefit of statin therapy observed in the JUPITER trial is likely reflective of the plaque-stabilizing effects of statins that have been previously observed.51 To further assess the role of inflammation in adverse cardiovascular events, the CANTOS trial randomized high-risk patients who had already experienced an MI with elevated CRP to treatment with canakinumab (a monoclonal antibody targeting interleukin-1-beta approved for treatment of several rheumatologic disorders) versus placebo.52 Treatment with canakinumab in this high-risk group who were already on high-intensity statin therapy resulted in a significant decrease in recurrent cardiovascular events. This benefit, however, came at the expense of life-threatening infection. Due to the high rates of these fatal infections, use of canakinumab is not recommended in the clinical management of these patients, though it does provide further evidence supporting the role of inflammation in cardiovascular disease. While additional studies are clearly necessary, there is a great deal of optimism in targeting inflammation as a novel pathway in the management of cardiovascular disease.
Risk Factor Modification
When atherosclerosis is identified, the immediate goals are to relieve symptoms through improvement of organ perfusion and to prevent plaque rupture. Aggressive risk factor modification to retard or prevent ongoing atherosclerosis is among the most important parts of long-term management. Smoking cessation, meticulous control of hypertension and diabetes, weight management, and aggressive lipid-lowering therapy are recommended. Lipid-lowering therapy with 3-hydroxy-3-methylglutaryl coenzyme A (HMG COA) reductase inhibitors has been shown to reduce mortality in patients with CAD, even when total cholesterol and LDL are only modestly elevated, which may reflect the anti-inflammatory role of statins in preventing plaque rupture.53,54 A low-fat, low-calorie diet may result in improved serum lipid levels as well as improved weight management, and a cardiovascular exercise program may result in reduced morbidity and mortality from CHD.55
Diagnosis
The diagnosis of chronic CAD is usually suspected from the clinical presentation. A history of exertional or resting symptoms including (but not limited to) chest tightness, jaw discomfort, left arm pain, dyspnea, or epigastric distress should raise the suspicion of CAD. Many patients deny “chest pain” per se, but the clinician should recognize subtle symptoms (such as dyspnea, diaphoresis, or epigastric distress) that may limit activity. Some patients with CAD have no symptoms that are identified during careful questioning, but have “silent ischemia” that is demonstrated by noninvasive testing.55 Careful attention should be directed to the risk factor profile for CAD, since the probability of atherosclerosis is increased in these individuals.56 A statistical extrapolation of the most recent National Health and Nutrition Examination Survey (NHANES) data suggested that oral healthcare professionals can effectively screen and identify patients that are unaware of their risk for developing CHD.57
Diagnostic testing begins with baseline 12-lead electrocardiography (ECG). Unfortunately, this is neither sensitive nor specific for the presence of CAD or prior MI. The presence of abnormal Q waves on the ECG may suggest prior MI, though these are not invariably present, and often only nonspecific changes of the ST segments or T waves are observed in patients with chronic CAD. Even a normal ECG does not exclude the presence of severe or even life-threatening CAD. Stress testing, often combined with nuclear or echocardiographic imaging modalities, remains the mainstay of a noninvasive diagnosis, though there is increasing evidence for use of cardiac computed tomography angiography (CTA) as the primary modality.58–60 Exercise testing with electrocardiographic monitoring is associated with a relatively low sensitivity and specificity for the detection of CAD and should be performed only if the resting ECG is normal. In low-risk patients, however, a negative exercise ECG strongly predicts a favorable clinical outcome.61 Even in patients with an intermediate to high clinical risk of CAD, achieving a relatively high workload during exercise with no ischemic ST depression in the ECG is also associated with a very low prevalence of significant ischemia.62
Single photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) with agents such as thallium 201 and technetium 99m sestamibi is used to assess coronary perfusion at rest and with physical stress. Since the uptake of these agents into the myocardium is an active process, ischemic or infarcted cells exhibit a reduced or absent uptake. A >70% stenosis of a coronary artery typically is associated with decreased myocardial perfusion on the stress images, but with normal myocardial perfusion at rest. This reversible defect is the perfusion pattern associated with stress-induced myocardial ischemia. A fixed defect demonstrates reduced myocardial perfusion both at rest and on exercise. Stress echocardiography detects myocardial ischemia by demonstrating regional differences in left ventricular contractile function during stress. Both myocardial perfusion imaging and stress ECG offer greater sensitivity and specificity than does exercise ECG alone, and they provide important prognostic information as well.
In patients who cannot exercise, exercise can be simulated with use of either coronary vasodilator agents (adenosine, dipyridamole, or regadenoson) or dobutamine, which directly increases myocardial contractility and heart rate. Vasodilator stress tests must be paired with imaging modalities that look directly at myocardial perfusion and therefore can be paired with SPECT-MPI, positron emission tomography (PET), and cardiac magnetic resonance imaging (MRI). Both PET and MRI are superior to SPECT in their sensitivity and specificity.63,64 While both PET and MRI have superior diagnostic accuracy, they are costlier, not widely available, and are typically reserved for very high-risk patients.
Cardiac CTA has emerged as an important diagnostic tool. Imaging the coronary arteries poses significant challenges owing primarily to the relatively small vessel caliber (2–4 mm) and normal cardiac motion. As such, it requires specialized scanners and protocols to achieve optimal images. It is now, however, a widely available method for detecting CAD, with an excellent sensitivity for detecting clinically significant stenoses. In addition, it has also been shown to be more cost-effective than stress testing.65 Given that it is a purely anatomic test, however, it does not address the potential physiologic significant of the obstruction, nor does it estimate the ischemic burden, both of which are key in decision-making. When compared to an initial up-front strategy of stress testing, data have been mixed, with the SCOT-HEART trial demonstrating that cardiac computed tomography (CT) was superior, whereas the PROMISE trial showed no difference.59 The benefit in the SCOT-HEART trial has been attributed to implementation of more aggressive therapy in patients who were found to have nonobstructive CAD that would have been otherwise missed on a functional test. Because of the apparent clinical equipoise paired with the decreased cost, the UK National Institute for Health and Care Excellence (NICE) guidelines have advocated cardiac CTA as the first-line diagnostic test.66 While this has not yet become the gold standard globally, it has nonetheless emerged as a very useful tool in select patients presenting with symptoms concerning for CAD.
Despite the multiple noninvasive tools that are currently available to evaluate for the presence of CAD, coronary angiography is often needed to define the anatomy and to assist in planning an appropriate management strategy for selected intermediate- to high-risk patients. At the time of coronary angiography, a purely anatomic assessment, validated functional testing (fractional flow reserve or FFR, instant wave-free ratio or iFR, and resting full-cycle ratio or RFR) can be performed to help assess the physiologic significance of an observed stenosis if indicated.67–69
Management
Medical Therapy
The management of chronic, stable CAD depends on several clinical factors, including the extent and severity of ischemia, exercise capacity, prognosis based on exercise testing, overall left ventricular (LV) function, and associated comorbidities such as diabetes mellitus. Patients with a small ischemic burden, normal exercise tolerance, and normal LV function may be safely treated with pharmacologic therapy. The front line of modern medical therapy includes the selected use of aspirin, beta-blockers, ACEis, and statins. These agents have been shown to reduce the incidence of subsequent MI and death.70,71 Nitrates, calcium-channel blockers, and ranolazine may be added to the primary agents to relieve angina in selected patients.
Revascularization
In the absence of severe disease, percutaneous coronary intervention (PCI) has been shown to improve symptoms of chronic ischemia without preventing death or MI.72 On the basis of available data, therefore, it seems appropriate to prescribe optimal medical therapy in most patients with CAD and stable angina, and reserve myocardial revascularization for select patients with disabling symptoms despite optimal medical therapy.73 Patients with a large ischemic burden are likely a specialized subset who may benefit from revascularization.74 In the highest-risk patients with severe CAD (left main coronary obstruction or diabetic patients with severe multivessel disease), coronary artery bypass surgery is likely superior to PCI,75–79 though PCI can be performed safely and may be a good option in certain patients.79,80
ACUTE CORONARY SYNDROMES
The sudden rupture of an atherosclerotic plaque, with ensuing intracoronary thrombus formation that acutely reduces coronary blood flow, underlies the pathophysiology of an ACS.81,82 This acute thrombus formation results in myocardial ischemia and subsequent infarction if there is a prolonged and severe reduction in blood flow. ACSs represent a continuous spectrum of disease, ranging from unstable angina (UA) to non-ST-elevation MI (NSTEMI) to acute ST-elevation MI (STEMI). If the intraluminal thrombus following acute plaque rupture is not completely occlusive, the corresponding clinical presentation is that of UA or NSTEMI.83 An MI is defined by the presence of myocardial necrosis identified by the presence of circulating cardiac biomarkers.26 The most common biomarker utilized clinically is cardiac troponins, which are a group of proteins found in cardiac myocytes. Troponin elevation is a very sensitive marker capable of detecting very minor levels of cardiac injury. The clinical presentation of both UA and NSTEMI is quite similar, with the latter being distinguished by the presence of a positive troponin. STEMI represents the most severe clinical scenario and reflects acute plaque rupture with prolonged and complete epicardial coronary obstruction.
Diagnosis of Acute Coronary Syndromes
The American College of Cardiology Foundation (ACCF) and the AHA recently updated their guidelines for the management of patients with ACS.84,85 ACS is typically diagnosed clinically. The patient’s history suggests a change in anginal pattern or ischemic symptoms at rest. Acutely, the ECG is the most important diagnostic tool to risk-stratify the patient and to make decisions regarding treatment. The presence of resting ST-segment depressions or dynamic T-wave changes in the distribution of an epicardial coronary artery associated with the typical clinical presentation is highly suggestive of UA or NSTEMI. The presence of ST-segment elevation when associated with classic clinical symptoms is the hallmark of an acute STEMI. Patients presenting with a history suggestive of an acute MI who have a left bundle branch block (LBBB) pattern on the 12-lead ECG are usually treated as if they had STEMI, given the difficulty of interpreting the ECG when this conduction delay is present. It is important to recognize, however, that the presence of a normal 12-lead ECG does not exclude the possibility of ACS in the correct clinical context.
As indicated earlier, cardiac troponins have emerged as a very sensitive tool to detect myocardial injury as soon as 3 hours after the onset of symptoms.86,87 The serum levels peak ~24–48 hours after the event and then gradually trend down over the new few days. While troponin elevation is very helpful in the diagnosis of UA and NSTEMI, it is not frequently useful in STEMI presentation when immediate revascularization is indicated. As the assays for troponin have become more and more sensitive, earlier identification of MI is now possible. The high sensitivity of our current troponin assays, however, is a double-edged sword, as low levels of troponin elevation are frequently seen in noncardiac illnesses (type 2 MI).26 In this setting, an acute stressor such as a gastrointestinal bleed or sepsis can lead to increased myocardial oxygen demand without an abrupt decrease in myocardial oxygen supply, resulting in a troponin elevation. In this setting, the myocardial ischemia is not driven by acute thrombosis but rather by the increased demand of the stressor. Because of the distinct differing pathophysiology, treatments will also be different. Distinguishing between ACS and a type 2 MI therefore is key and is essentially a clinical diagnosis.
Initial Management for Unstable Angina and NSTEMI
The treatment of the unstable coronary syndromes should focus on the relief of myocardial ischemia and the institution of pharmacologic therapy targeting the underlying thrombotic mechanism (Table 14‐8). Aspirin should be promptly administered to inhibit platelet function. The selective use of beta-blockers may relieve ischemia by lowering heart rate and BP, which reduce myocardial demand.
Beta-blockers are also antiarrhythmic agents and can suppress associated malignant ventricular arrhythmias. Beta-blockers should not be administered to those with acute decompensated heart failure, bradycardia, heart block, or severe bronchospasm. Sublingual or intravenous nitroglycerin decreases LV preload and dilates the epicardial coronaries arteries, thereby decreasing myocardial ischemia.84
In troponin-positive high-risk patients, there is robust clinical evidence of improved outcome when, in addition to aspirin, a second antiplatelet agent is administered. These include clopidogrel (Plavix) or ticagrelor (Brilinta). The choice of these agents depends on the relative degree of ischemic versus bleeding risk. It is important to know that these are potent and long-acting antiplatelet agents whose use is associated with major bleeding risk if a patient is to undergo emergent surgery.84
There is some evidence that high-risk patients with ACS will benefit from treatment with intravenous unfractionated heparin or subcutaneous low molecular weight heparin such as enoxaparin (Lovenox).84 The short-acting intravenous unfractionated heparin is preferred in high-risk patients who may need emergent cardiac catheterization and/or bypass surgery, whereas enoxaparin may have some advantage in all other patients with ACS. Procedural outcomes are improved when dual antiplatelet therapy and heparin are used during angioplasty and stenting (see Table 14-8 for a list of these agents).
Table 14‐8 Common antithrombotic agents.
| Generic Name | Route of Administration |
|---|---|
| Antiplatelet | |
| Aspirin | Oral |
| ADP Receptor Antagonists | |
| Clopidogrel | Oral |
| Prasugrel | Oral |
| Ticagrelor | Oral |
| Cangrelor | Intravenous |
| Glycoprotein IIb/IIIa Receptor Asntagonists | |
| Abciximab | Intravenous |
| Eptifibatide | Intravenous |
| Tirofiban | Intravenous |
| Anticoagulants | |
| Unfractionated heparin | Subcutaneous/intravenous |
| Low molecular weight heparin (enoxaparin, dalteparin) | Subcutaneous |
| Lepirudin | Intravenous |
| Bivalirudin | Intravenous |
| Warfarin | Oral |
| Direct Oral Anticoagulants | |
| Dabigatran | Oral |
| Betrixaban | |
| Apixaban | Oral |
| Rivaroxaban | Oral |
| Edoxaban | Oral |
ADP, adenosine diphosphate.
In high-risk patients with unstable angina or NSTEMI, implementation of an early invasive strategy (within 24–48 hours) with coronary angiography and PCI is associated with improved outcomes and is the most typical strategy. In lower-risk patients where the diagnosis is less clear clinically or who may be poor candidates for angiography/PCI, further risk stratification with pharmacologic stress testing may also be reasonable.84
Initial Management for STEMI
Given that the pathophysiology involved in STEMI is due to complete epicardial coronary artery obstruction, the major goals of therapy are to provide revascularization as quickly as possible. In the current era, the therapy of choice is PCI, with a goal to restore perfusion within 90 minutes of clinical presentation (so-called door-to-balloon time). In situations where PCI is not expected to be available within 120 minutes of first presentation, thrombolytic therapy is recommended.85,88 Thrombolysis with streptokinase, tissue plasminogen activator, and reteplase have all been shown to improve coronary blood flow and to reduce mortality.89,90 Prospective randomized trials have shown that PCI with stenting in patients with STEMI is superior to thrombolytic therapy when it is completed within 1–2 hours of clinical presentation. Only if a patient with STEMI presents to a center that lacks the ability to perform emergent PCI is thrombolytic therapy the treatment of choice if immediate transfer to a PCI center cannot be arranged. All patients who have received thrombolytic therapy, however, should be immediately transferred to a PCI center.85,88
Post-Acute Coronary Syndrome Management
All patients with ACS should be treated with low-dose aspirin (81–100 mg) indefinitely. There is evidence that treatment with a second antiplatelet agent (clopidogrel) is beneficial even if PCI is not performed. If PCI is performed, dual antiplatelet therapy is continued for at least 6–12 months.84,85,88,91 Treatment for longer duration has been associated with reduced ischemic events, though at the expense of increased bleeding.92 The Dual Antiplatelet Therapy (DAPT) score has been established as a tool to help guide decision-making, balancing these competing risks on an individual patient basis.93 In patients for whom the decision has been made to continue dual antiplatelet therapy beyond the initial 6–12 months, temporary interruption if necessary for procedures can be done safely, though consultation with the patient’s cardiologist is still recommended. Initiation of a high-intensity statin during the index hospitalization has also been shown to be associated with improved outcomes, though it is not clear that the benefit is necessarily due to the acute exposure to high-intensity statin rather than chronic therapy.33 Aggressive lipid management after ACS is a key component of secondary prevention, with recent data demonstrating significant incremental risk reduction with LDL lowered to as low as 30 mg/dL with combined use of statins, ezetimibe as well as the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors evolocumab and alirocumab.31,32,94 Beta-blockers are typically continued after ACS, and in patients with LV dysfunction, ACEi/ARBs have a demonstrated benefit in preventing adverse remodeling. Outpatient cardiac rehabilitation is key to improving functional outcomes after discharge and should also be routinely recommended after an ACS event.84,85,88,91
Dental Management Considerations for Patients with Coronary Artery Disease
Several considerations need to be addressed for dental patients with CAD.95 The primary concern is to prevent ischemia or infarction. The risk for such an event is determined by several factors, including the degree and type of CAD (i.e., stable vs. unstable, past history of angina or MI). Patients with CAD are at increased risk of demand-related ischemia from an increased heart rate or BP, as well as for plaque rupture and acute unstable coronary syndromes. Anxiety will increase the heart rate and BP, and can provoke angina or ischemia,96 but this risk is relatively low during outpatient dental procedures.
There is longstanding dogma in dental practice that patients who have had an MI within the past 6 months should not have elective dental procedures, but this concern is largely based on a misinterpretation of a study of patients with CVD undergoing noncardiac surgery under general anesthesia. A study of a large Medicare population who underwent a dental procedure within 30–180 days after an ischemic vascular event were not found to be at increased risk of a second event.97
Numerous studies have indicated the influence of circadian variation and other triggers for acute coronary events, to include mental stress, hostility, anger, and depression.98 Most such events occur between 6:00 am and noon. It has been proposed that sympathetic nervous system activation and an increased coagulative state may be precipitating factors.99 Medications designed to prevent these events include beta-blockers, aspirin, and antihypertensives. Dental care for high-risk patients might ideally be provided in the early afternoon.
Recent protocols suggest that patients may be safely treated in an outpatient dental setting 30 days after an MI unless the patient has decompensated CHF. Considerations for dental patients who have undergone CABG procedures or coronary stenting are similar to those who have had an MI; that is, there are no data to support waiting as long as 6 months before resuming dental treatment. Following open heart surgery (e.g., CABG), however, sitting in a dental chair may be painful, even several weeks after surgery. Elective dental care should therefore be postponed until the patient can sit comfortably for the required time period.
Elective procedures, especially those requiring general anesthesia, should be avoided for at least a month following an MI, as there is a small increased risk of reinfarction.100 These dental procedures can be undertaken provided the patient is able to continue on their current antithrombotic therapy uninterrupted. Limited data suggest that the acute risk of administering local anesthesia without vasoconstrictor for 3 weeks after an uncomplicated MI is low, but if epinephrine-containing local anesthetic is necessary, it may be desirable to discuss this with the patient’s primary care physician or cardiologist.
Protocols to reduce anxiety should be considered, according to the level of anticipated stress. The patient’s nitroglycerin tablets or spray should be available during the procedure. In some situations, patients may be on one or more drugs that interfere with hemostasis. Antiplatelet drugs, such as aspirin, clopidogrel, prasugrel, or ticagrelor, are frequently used in patients with ACS and in all patients after coronary artery stenting. The combination of dual antiplatelet therapy (e.g., aspirin and clopidogrel) is usually continued for a minimum of 4 weeks after placement of a bare metal stent, and for a minimum of 6–12 months following placement of a drug-eluting stent.101 There are limited data addressing the risk from dental procedures performed following coronary stenting.102 If the procedure can be performed safely without interruption of the recommended antithrombotic therapy, it is reasonable to move forward with elective dental procedures after 4 weeks. If the procedure cannot be performed safely on dual antiplatelet therapy, consultation with the patient’s cardiologist is recommended to weigh the relative risks of dual antiplatelet therapy interruption with delay in the dental procedure, as these are nuanced conversations. In general, purely elective procedures requiring interruption of dual antiplatelet therapy will be delayed by 6–12 months, though more urgent procedures can be considered after 3 months. The concern with early interruption of dual antiplatelet therapy is related to the risk of stent thrombosis in the early time period. During this time, the stent has not yet been fully endothelialized, making it highly susceptible to thrombosis without use of both aspirin and a second antiplatelet agent. Premature discontinuation of antiplatelet therapy has been significantly associated with adverse cardiac events, such as MI and death.103
Dental Management Considerations for Patients with Angina
From the standpoint of the patient’s history, it is important to know whether angina occurs at rest, and if there are precipitating factors such as exercise, climbing stairs, or emotional stress. Patients should also be asked about the frequency, duration, timing, severity of attacks, and the response to medication. Dental healthcare providers should be aware that angina may present as jaw discomfort, often on the left side. Other cardiac conditions important to the medical history include the presence of noncoronary vascular disease and if the patient has a pacemaker or defibrillator. Patients with angina may be on one or more of the following drugs: nitrates or beta-blockers, which can cause conduction disturbances and fatigue; and calcium-channel blockers, which have side effects including bradycardia, worsening heart failure, headache, and dizziness. Respiratory depressants such as opioids, barbiturates, and other sedatives can worsen the cardiovascular status and should be avoided.
Elective dental treatment is reasonable if the angina is stable without change in severity or frequency over several months. If there is a change in the pattern of angina with more frequent episodes, more frequent sublingual nitroglycerin use, or angina with less exertion, this is concerning for unstable angina. Elective dental treatments should be avoided, and the patient should be referred to their cardiologist for urgent evaluation.
STRUCTURAL HEART DISEASE
Valvular Heart Disease
VHD occurs in ~2.5% of the American population and each year more than 100,000 heart valve procedures are performed.3 It is typically first identified by the presence of murmur on auscultation. With early identification and appropriate referral, the majority of patients with VHD will live a normal lifespan.
Mitral Valve Disease
The mitral valve sits between the left atrium and left ventricle and when functioning normally, allows for filling of the left ventricle during diastole and during ventricular systole prevents backward flow back into the left atrium. The mitral valve apparatus is complex and comprises two leaflets (anterior and posterior), the mitral annulus, chordae tendinae, and the papillary muscles (see Figure 14‐2). Mitral regurgitation (MR) is the most common heart valve disease and is the result of failure of the mitral valve to prevent backward flow during ventricular systole.3 Mitral stenosis (MS) results from progressive abnormalities in the mitral valve, leading to impedance of normal blood flow from the left atrium into the left ventricle during filling. In addition to the hemodynamic alterations that are present in patients with these conditions, there are additional issues with regard to the prevention of bacterial endocarditis.
Etiology and Pathophysiology
MR is the result of abnormal closure of the mitral leaflets.104 It can result from intrinsic abnormalities of the valve leaflets themselves, termed primary MR. The most common causes of primary MR include mitral valve prolapse (MVP), calcific degenerative disease, rheumatic heart disease (RHD), endocarditis, and the use of anorectic agents such as fenfluramine and phentermine (fen-phen).105
Figure 14‐2 Mitral valve anatomy. The mitral valve consists of the mitral annulus, anterior and posterior leaflets, chordae tendinae, and the papillary muscles. Mitral regurgitation (MR) may be due to a disease process that primarily affects the valve leaflets (primary MR) such as a mitral valve prolapse or due to alterations in the structure/function of the left ventricle or atrium (secondary MR) such as those induced with a dilated cardiomyopathy.
Source: From Otto, C. M. (2001). Evaluation and Management of Chronic Mitral Regurgitation. New England Journal of Medicine, 345(10), 740–746. © 2001, Massachusetts Medical Society.
MVP, as mentioned, is a common cause of primary MR, though the clinical syndrome is highly variable. It occurs in ~2.5% of the population106,107 and is most commonly due to redundant mitral leaflet tissue associated with myxomatous degeneration. MR can occur in the setting of MVP, either due to prolapse of the affected leaflet with associated chordal elongation or due to rupture chordae. The severity of MR is highly variable, with the minority of patients developing severe MR. While this can be seen in patients with connective tissue disorder such as Marfan’s and Ehlers–Danlos syndromes, it is typically seen in isolation. MVP may be associated with arrhythmias including premature ventricular complexes, supraventricular tachycardias, and atrial fibrillation, as well as malignant ventricular arrhythmias.104
MR can also occur due to structural changes in the left atrium or left ventricle, termed secondary or functional MR. Secondary/functional MR is typically seen in the presence of severe LV dysfunction resulting in apical displacement of the papillary muscles and annular dilation, or in severe left atrial dilation with resultant changes in the mitral valve annular anatomy. This distinction between primary and secondary MR is critical, as treatments vary widely.
In the presence of chronic MR, resistance to ventricular emptying is reduced as the LV is able to eject into the low-impedance left atrium as opposed to the aorta. To preserve forward flow, LV stroke volume and diastolic LV filling increase. This volume load is well accommodated by the LV for quite some time; however, if left unchecked, it ultimately progresses to LV dilation, LV dysfunction, and symptomatic CHF.
The two most common causes of MS are RHD or calcific degeneration. While uncommon in the developed world, RHD remains the dominant form of VHD in developing countries.108 In RHD, there is characteristic thickening and fusion of the mitral commissures as well as thickening and calcification of the leaflets and subvalvular apparatus. This results in a restriction to LV inflow, subsequent left atrial hypertension and enlargement, atrial arrhythmias, secondary pulmonary hypertension, and right ventricular dysfunction.
Diagnostic Evaluation
MR is typically first identified on physical examination. MR is characterized by a systolic murmur heard best at the apex, while MS manifests as an apical diastolic rumble. Once identified on physical examination, transthoracic echocardiography (TTE) remains the mainstay of noninvasive diagnosis in patients with mitral valve disease, and Doppler techniques are extremely useful in establishing the severity of stenosis or regurgitation.109 Because of the dynamic nature of mitral valve disease, exercise stress echocardiography can also be useful to assess for changes in severity of either regurgitation or stenosis at peak exercise, or to look for evidence of exercise-induced pulmonary hypertension, a high-risk feature in both MR and MS. Transesophageal echocardiography (TEE) is useful in further defining the mechanism of MR or MS, better assessing the severity of the hemodynamic lesion,110 and treatment planning. TEE offers improved image quality due to the proximity of the transducer to the mitral valve and left atrium. Cardiac catheterization has a limited role in the diagnosis of MR and is primarily reserved for those patients who are referred for cardiac surgery to assess for significant CAD.111 In MS, direct assessment of the pressure gradient across the mitral valve via hemodynamic catheterization can be useful in challenging cases.
Treatment
The ACC, AHA, and ESC have published guidelines for the management of VHD.112,113 Medical therapy for primary MR is quite limited and decisions regarding treatment typically hinge on the timing of intervention. Surgical valve intervention is currently recommended in patients who are symptomatic from severe primary MR or in asymptomatic patients with progressive LV dilation or dysfunction. There is evidence to suggest that patients with pulmonary hypertension or atrial fibrillation associated with isolated primary severe MR may also benefit from surgical intervention, and guidelines indicate that surgery is also reasonable in this patient population. Primary MR is surgically treated with either repair or replacement. Mitral repair is usually accomplished with the resection of the prolapsing or flail segment and placement of an annuloplasty ring. Due to improved surgical outcomes with repair compared to replacement, repair is preferred if technically possible. If repair is not technically feasible, replacement with either a biologic or mechanical prosthesis may be necessary. In patients who are prohibitive or high-risk surgical candidates, transcatheter mitral valve repair (with use of the MitraClip device) is currently available.114 In select patients, transcatheter mitral replacement can also be considered.115 These procedures are performed in a minimally invasive fashion via the femoral veins and do not require cardiopulmonary bypass. Additional devices are currently being investigated for the percutaneous treatment of mitral valve disease.116,117
Intervention for secondary MR is more controversial, as the primary driver of the MR in these pathologies is not the mitral valve itself. The benefits for mitral valve surgery in patients with isolated secondary MR have not been demonstrated to outweigh the surgical risks, and therefore it is rarely performed. In patients undergoing cardiac surgery for an alternative reason who also have severe secondary MR, mitral valve replacement (over repair) is typically also performed. The use of the MitraClip in secondary MR has recently been evaluated in two randomized clinical trials with conflicting results, though in the select patient population, transcatheter mitral valve repair is also reasonable.118,119
Stay updated, free dental videos. Join our Telegram channel
VIDEdental - Online dental courses
