Q&A: Daniel M. Blumenthal, MD, MBA Substance Abuse and Cardiovascular Disease
Author: Mark Gold, MD
Interviewed by Mark Gold, MD
FEATURED ADDICTION EXPERT:
Daniel M. Blumenthal, MD, MBA
Attending Physician, Division of Cardiology, Massachusetts General Hospital
Instructor of Medicine at Harvard Medical School
Associate Chief Medical Officer at Devoted Health
Do FDA-approved psychostimulants increase the risk of cardiovascular events?
There is no convincing evidence that FDA-approved psychostimulants (e.g. methylphenidate, dextroamphetamine, amphetamine salts, and atomoxatine) increase the risk for cardiovascular events among patients without pre-existing cardiovascular disease (CVD). However, among those with pre-existing heart disease, including arrhythmias, coronary artery disease, heart failure, or in patients for whom an increase in heart rate or blood pressure could be harmful, psychostimulants may increase the risk for cardiovascular events.
How does cocaine end up as the number two cause of drug deaths, just behind opioids? Excluding adulteration with opioids, how does cocaine kill you?
The effects of cocaine on the cardiovascular system can be grouped into acute and chronic processes. Cocaine use can cause one or more of several acute, life-threatening cardiovascular effects. The most common is myocardial ischemia or infarction (e.g. a heart attack). Cocaine can induce a heart attack through one of several mechanisms. First, cocaine causes arterial (including coronary artery) vasoconstriction, which can lead to coronary vasospasm. Second, cocaine activates platelets, which increases the risk of thrombosis (including coronary thrombosis). Third, cocaine use produces an adrenergic surge which induces tachycardia (high heart rate) and hypertension. High heart rate and hypertension both increase myocardial oxygen demand, which can cause supply-demand mismatch and precipitate myocardial ischemia or infarction. Fourth, vasospasm or stress associated with cocaine use can also precipitate coronary artery plaque rupture (the mechanism underlying most classic heart attacks). Two thirds of heart attacks due to cocaine occur within three hours of cocaine use; the risk of a heart attack is 24-fold higher than normal in the first sixty minutes after using cocaine. Cocaine has several other potentially devastating acute effects, including stroke, aortic dissection (e.g. dissection of the major artery connecting the heart to the rest of the body), life threatening heart arrhythmias, and myocarditis which can also occur with chronic use. Chronic cocaine can result in accelerated atherogenesis (i.e. accelerated plaque buildup in the coronary arteries), hypertrophy of the left ventricle, dilated cardiomyopathy, aortic aneurysms, and coronary aneurysms.
Patients who are acutely intoxicated with cocaine and present with chest discomfort should be referred to an emergency room immediately for evaluation. They should undergo a chest-x-ray, an electrocardiogram, blood work to evaluate for evidence of a heart attack and non-myocardial muscle breakdown (e.g. rhabdomyolysis), and to assess kidney function, white and red blood cell counts, and liver function. Cocaine intoxication is diagnosed if and when patients report recent cocaine use and through serum and urine toxicology screens (which should be performed immediately as well). If a clinician suspects that a patient is acutely intoxicated with cocaine, treatment should not be withheld while waiting for the results of the toxicology screen. Patients with acute cocaine intoxication and symptoms concerning for cerebrovascular or other cardiovascular sequelae of cocaine intoxication may also need additional imaging to assess for evidence of damage to the heart, aorta, or other blood vessels.
In terms of treatment, these patients should receive benzodiazepines to help mitigate the adrenergic surge. If chest pain due to myocardial ischemia is suspected, sublingual nitroglycerin should be administered. Ongoing ischemic symptoms, as well as hypertension and tachycardia (drivers of myocardial oxygen demand) should be treated with calcium channel blockers (i.e. diltiazem or verapamil). Beta blockers should ideally be avoided until there is no cocaine remaining in the patient’s system. If beta blockers must be used, we recommend using either labetalol or carvedilol, which are non-selective inhibitors of both alpha and beta receptors (note: other beta blockers that are selective for beta receptors are contraindicated due to a theoretical risk that selective beta blockade could lead to unopposed alpha-mediated arterial vasoconstriction, which could precipitate marked hypertension and even peripheral and splanchnic ischemia). Alternative, and highly effective, agents for treatment of hypertension include IV nitroglycerin (which should also be used if the patient has chest pain) and IV nitroprusside. Phentolamine, an alpha blocker, can be used for refractory hypertension. Patients presenting with chest pain should also receive a full dose chewable aspirin (325 mg) and 80 mg of atorvastatin (if available). Patients with ECG changes consistent with myocardial ischemia or infarction and/or elevated blood levels of cardiac biomarkers should be managed identically to patients with non-cocaine induced myocardial ischemia and infarction.
Cocaine and methamphetamine addicts often have heart disease. Why? How is a diagnosis made?
Cardiac sequelae are the second most common cause of death (behind overdose) in patients who use methamphetamines (“meth”). Like cocaine use, use of methamphetamines can produce both acute and chronic cardiovascular disease. Acute intoxication with methamphetamines produces a hyperadrenergic state, not unlike having a pheochromocytoma. The hypertension and tachycardia that result can lead to myocardial ischemia and infarction, aortic dissection, malignant arrhythmias, Takotsubo’s (stressinduced) cardiomyopathy, and cardiac arrest. Chronic methamphetamine use can lead to hypertrophic cardiomyopathy (due to persistent severe hypertension) or dilated cardiomyopathy (due to the drug’s toxic effects on myocardium), and the clinical syndrome of heart failure. In addition, chronic meth use can also cause pulmonary arterial hypertension (PAH). Meth-associated PAH is a devastating disease, with five year mortality rates above 50%.
Diagnosing and managing acute methamphetamine intoxication:
Patients who present with suspected acute methamphetamine intoxication should undergo a full physical exam, electrocardiogram, and basic lab work (including basic metabolic panel, blood counts, clotting times (prothrombin time and international normalized ratio), liver function tests, creatine phosphokinase (CPK), urinalysis, and urine and serum toxicology screens). Amphetamine intoxication or toxicity is ultimatelydiagnosed by confirming the presence of amphetamines in urine or serum. However, if patients present with signs and symptoms which raise concern for amphetamine intoxication—including hyperthermia, agitation, hypertension, and tachycardia—treatment should not be delayed while waiting for these test results to return.
If there is concern for myocardial ischemia or infarction (for example, if the patient complains of chest discomfort or shortness of breath or the ECG shows ischemic changes), then cardiac biomarkers should be checked as well (i.e. troponin I or T). Acute methamphetamine intoxication with secondary sequelae (i.e. agitation, hypertension, tachycardia) should be managed initially with sedatives (benzodiazepines and 2nd generation atypical antipsychotics).
Hyperthermia should be managed aggressively by controlling core body temperature with sedatives and, if necessary, with paralysis and intubation (but antipyretics should not be used).
Rhabdomyolysis is common, and a CPK level should always be checked in patients who are acutely intoxicated with meth. If the hypertension is refractory to treatment with an adequate trial of sedation, then nitrates and/or phentolamine should be used. Calcium channel blockers can also be used, and are effective agents for managing tachycardia that persists despite sedation. Beta-blockers should be avoided in the acute setting to avoid precipitating unopposed alpha-mediated vasoconstriction (via identical mechanisms to those described above). If beta blockers are necessary for chronic management of a different disease process (e.g. cardiomyopathy or coronary artery disease), then labetalol or carvedilol are the preferred agents due to their partial alphaantagonism. Myocardial infarction in the setting of methamphetamine intoxication should be managed per evidence-based guidelines for the management of heart attacks, and as described above (for cocaine). The one exception is that, if heart rate control is needed, calcium channel blockers, not beta blockers, should be used. Interestingly, monoclonal antibodies against methamphetamine have been developed and are currently in clinical trials.
Chest pain in the setting of acute methamphetamine intoxication should raise concern not only for myocardial infarction, but also for acute aortic dissection. Methamphetamine abuse is the second most common cause of acute fatal aortic dissection in the US, after hypertension. Unlike chest discomfort due to myocardial ischemia, which often starts as mild or moderate discomfort and worsens progressively over minutes-hours, chest discomfort due to aortic dissection is typically extreme from the outset.
What does the patient PE and EKG look like if a patient has overdosed on opioids? What about when injected with Narcan and reversed? Does Methadone, when given as a MAT, have QT and other effects on the heart? What about Suboxone and the heart?
Opiate overdose can precipitate respiratory depression and coma. The pupils will be mioitic, or “pinpoint.” Patients commonly experience mild hypotension as well. The electrocardiogram classically shows sinus bradycardia with nonspecific changes. Approximately 20% of patients will have prolongation of the QT interval. Administration of an adequate dose of Narcan rapidly reverses the respiratory depression, miosis, and coma, and can also lead to improvements in blood pressure and an increase in heart rate. However, Narcan is short acting and the reversal is temporary. Thus, patients must be monitored following Narcan administration to determine if they need subsequent doses, or even initiation of an IV naloxone drip. Methadone may also cause QT prolongation but is an uncommon cause of Torsades Des Pointes, the potentially fatal arrhythmia that can result from QT prolongation. Suboxone can also cause hypotension, including orthostatic hypotension, and should be used with caution in patients with established cardiovascular disease (e.g. coronary artery disease). However, I am unaware of any unique cardiovascular side effects associated with suboxone use.
Does smoking have effects on the heart?
Smoking is an extremely strong and independent risk factor for heart disease, stroke, and peripheral artery disease. Smoking increases the risk of these conditions in a dose dependent fashion, and no amount of smoking is safe. People who smoke less than five cigarettes per day are at increased risk for myocardial infarction relative to non-smokers. The incidence of myocardial infarction among men and women who have smoked at least twenty cigarettes per day for any period of time is three fold and six fold higher, respectively, than the incidence of myocardial infarction in never smokers. More generally, smoking increases the risk of coronary artery disease, heart attack, arterial aneurysms, aortic dissection, blood clots, carotid artery stenosis, upper and lower extremity ischemic claudication, and death. Smoking’s deleterious cardiac, cerebrovascular, and peripheral vascular effects are the result of a variety of mechanisms that contribute to atherogenesis. Smoking is associated with insulin resistance and oxidization of low-density lipoprotein (LDL-c, or bad cholesterol). Oxidization of LDL-c makes it more proatherogenic. Smoking also activates the sympathetic nervous system which increases heart rate and blood pressure and leads to peripheral vasoconstriction. Moreover, smoking increases inflammation, which activates platelets and creates a prothrombotic milieu. Furthermore, smoking damages blood vessel walls, rendering them less elastic and promoting premature arterial stiffening; in addition, smoking promotes endothelial dysfunction, which impairs the ability of coronary arteries to vasodilate. The risks of cardiovascular, cerebrovascular, and peripheral artery disease and associated events decrease significantly and relatively rapidly with smoking cessation.
What about cannabis addicts or chronic smokers and the cardiologist?
While we know relatively less about the effects of marijuana on the cardiovascular system, there is significant and growing interest in understanding how marijuana use impacts heart and blood vessel function. We do know that smoking marijuana leads to an acute, four- to five-fold increase in the risk of myocardial infarction in young men. This risk persists for approximately 60 minutes following inhalation. Daily cannabis use is associated with a 1.5%-3% annual increase in the risk of myocardial infarction. There is some evidence that the mechanism underlying this increased risk is a higher likelihood of experiencing coronary artery vasospasm (as opposed to accelerated atherogenesis).
The physiologic effects of marijuana may surprise some people. Marijuana intoxication typically leads to a slowing of the reflexes, and the appearance of a relaxed state. However, marijuana use actually stimulates the sympathetic nervous system, which leads to tachycardia, the release of systemic catecholamines, and increased myocardial oxygen demand. At the same time, marijuana use increases supine systolic and diastolic blood pressure, and increases the likelihood of experiencing orthostatic hypotension. There is also some evidence that marijuana use activates platelets by modulating the endocannabinoid system. Longitudinal prospective studies of cannabis users have failed to reveal evidence that chronic cannabis use leads to significant alterations body mass index, blood pressure, total cholesterol, high density lipoprotein, triglycerides, or blood glucose levels. There is no consistent evidence that marijuana use increases cardiovascular mortality. We know relatively little about whether the mode of use (i.e. smoking vs. ingestion) modifies the effects of marijuana on the cardiovascular system.
Ketamine is being used off label for depression. What are the cardiovascular risks and concern when this is done?
This is an extremely interesting question. Ketamine is a sympathomimetic. Studies of the cardiovascular effects of Ketamine have found that the drug increases cardiac output by up to 50% in healthy subjects. However, among sicker patients, the drug’s effects appear to be more variable, with some patients experiencing augmented ventricular performance, and others demonstrating some impairment in left ventricular function due to Ketamine use (among coronary artery bypass graft patients, for example, induction of anesthesia with Ketamine has been shown to significantly reduce left ventricular stroke volume). Ketamine does consistently produce tachycardia and this simple fact should lead us to be cautious about using it to treat depression in patients with obstructive coronary artery disease or congestive heart failure. The cardiovascular effects of Ketamine remain incompletely characterized, and the prospect of widespread use to treat chronic illnesses like depression heightens the need to more clearly elucidate how Ketamine effects the cardiovascular system.
Withdrawal from opioids is associated with hypertension and tachycardia. Is this a concern?
Yes—the hypertension and tachycardia which occur during opioid withdrawal can undoubtedly stress the cardiovascular system. Patients with a history of coronary artery disease (particularly those with a history of angina), patients with congestive heart failure, and those with aortic aneurysms should be monitored closely during the withdrawal period for new or worsening cardiovascular symptoms. In addition, patients’ home cardiovascular medication regimens, including beta blockers, antihypertensives, and anti-anginals (i.e. nitrates) should ideally be continued during the withdrawal period if possible in order to blunt the physiologic effects of opioid withdrawal.
Are any drug withdrawal syndromes a concern to a cardiologist?
In general, most withdrawal syndromes result in some degree of heightened sympathetic tone, which can produce hypertension and tachycardia. In patients with serious chronic cardiovascular illness, including coronary artery disease, congestive heart failure, valvular disease (i.e. aortic stenosis, mitral stenosis, or mitral regurgitation), or arrhythmias, including atrial fibrillation or paroxysmal supraventricular tachycardia, this sympathetic surge can precipitate symptoms or even acute decompensations. So, and this is a key point, it is the patient substrate which matters more than the specific withdrawal syndrome. Put another way, if the patient has significant cardiovascular comorbidities, any withdrawal syndrome may be dangerous.
In general, I worry most about alcohol withdrawal for a few reasons. First, alcoholics regularly live with multiple comorbidities, including cardiovascular comorbidities like atrial fibrillation and heart failure (which may be due to an alcoholic cardiomyopathy). I have seen alcohol withdrawal precipitate new or recurrent atrial fibrillation, and lead to acute heart failure decompensations in patients with underlying alcoholic cardiomyopathies. Second, alcohol withdrawal is by far the most mortal withdrawal syndrome; seizures due to withdrawal, or delirium tremens, carry a significant risk of mortality in patients without underlying cardiovascular illness, and may be even more dangerous in patients who are suffering from concomitant cardiovascular disease. Third, many alcoholics are poorly nourished, and have significant electrolyte disturbances, including hypokalemia (which is a risk factor for ventricular arrhythmias). The wasting of magnesium that occurs in alcoholics is particularly concerning, because potassium repletion is ineffective in the absence of adequate serum magnesium levels. Thus, when checking basic electrolytes in an alcoholic (e.g. sodium, potassium, bicarbonate, chloride, etc.), be sure to also check magnesium levels. And, if an alcoholic is hypokalemic and you don’t have a serum magnesium level, replete the magnesium before giving potassium (or alongside the potassium). A little extra magnesium won’t have any adverse consequences, but failing to replete magnesium could result in failure to correct the low potassium level, which could have serious consequences.
Which patients should an addiction rehab send to a cardiologist for evaluation?
This is a difficult question to answer with high specificity. First, any patient with new or concerning cardiovascular symptoms or confirmed cardiovascular disease, including 1) exertional chest discomfort; 2) documentation of a new or recurrent arrhythmia; 3) new exertional shortness of breath; and/or 4) new signs or symptoms of congestive heart failure, including exertional shortness of breath, new or progressive lower extremity edema, and/or paroxysmal nocturnal dyspnea or orthopnea, should be evaluated by a cardiologist. In addition, anyone with a syncopal event without a prodrome (i.e. sudden, unexplained, and unheralded syncope) or with a history of complex congenital heart disease should be referred to see a cardiologist. Patients with chronic, stable cardiovascular comorbidities, including coronary artery disease (with or without angina), congestive heart failure, peripheral artery disease (with or without claudication), valvular disease (i.e. aortic stenosis or mitral regurgitation), and/or cerebrovascular disease do not necessarily need to be seen by a cardiologist while they are in Rehab, and provided they remain stable and are able to continue their long term outpatient treatment regimens for these conditions. However, a rehab should generally have a low threshold to engage a cardiologist in the management of any patient with complex, chronic cardiovascular disease.
What are the CVD effects of alcohol use, abuse, and addiction? Alcohol users have a variety of CV effects including noticing that their heart skips a beat or so…is this related to alcohol abusers or alcoholics heart blocks?
Modest alcohol consumption—two or fewer drinks per night for a man, and one drink per night for a woman— has been shown to be healthy, and may even reduce all-cause mortality and mortality due to cardiovascular disease. However, when consumed in greater quantities, alcohol is a cardiotoxin. People who abuse or are dependent on alcohol have a heightened risk of arrhythmias—including atrial fibrillation, atrial flutter, and ventricular arrhythmias (due to electrolyte abnormalities or an alcoholic cardiomyopathy)—and alcoholic cardiomyopathy. Alcoholic cardiomyopathies can be profound; I have taken care of daily drinkers who present with severe, bi-ventricular dysfunction and left ventricular ejection fractions (LVEF) of 10%-15% (normal is 52- 70%). Importantly, alcoholic cardiomyopathy is usually not this fulminant. Many daily drinkers may suffer from very mild, and even subclinical, forms of this cardiomyopathy, and their LVEF may be normal.
However, in these patients the cardiotoxic effects of alcohol may still predispose to premature atrial and ventricular beats—which they may experience, and describe, as “skipped beats.” As noted above, alcoholic cardiomyopathy increases the risk of both atrial and ventricular arrhythmias, and prior work shows that the risk of ventricular tachycardia in alcoholic cardiomyopathy is comparable to that seen in patients with idiopathic dilated cardiomyopathies. The electrolyte abnormalities commonly found in alcoholics—most notably hypomagnesemia and hypokalemia— further compound the risk for these arrhythmias.
Fortunately, alcoholic cardiomyopathy is usually a reversible process; I have multiple patients whose LVEF has improved from this 10%-15% range (while drinking daily) to 50% or more (essentially normal) after one-two years of abstinence from alcohol and adherence with traditional heart failure therapies. Alcoholic cardiomyopathy may at times reach a point of irreversibility, of course, but, broadly speaking, it has a very favorable prognosis if long term abstinence can be achieved.
Alcoholic abuse/dependence is also associated with a modestly increased risk for myocardial infarction, particularly in patients with pre-existing cardiovascular disease.