Article

The evaluation and management of decompensated hypertrophic cardiomyopathy in the emergency department

American Journal of Emergency Medicine 36 (2018) 2286-2288

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American Journal of Emergency Medicine

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Review

The evaluation and management of decompensated hypertrophic cardiomyopathy in the emergency department

Matthew Gardner, PharmD, a,?, Vidya Nair, PharmD, MBA-MPH Candidate 2019 a,

Daniel Hu, PharmD b, Susan Derry, MD, MN c

a Emergency Medicine, Providence St. Peter Hospital, United States of America

b Emergency Medicine, Critical Care, Providence St. Peter Hospital, United States of America

c PSPH Emergency Medicine physician group CME, United States of America

a r t i c l e i n f o

Article history:

Received 18 April 2018

Received in revised form 27 August 2018

Accepted 1 September 2018

Keywords:

Hypertrophic cardiomyopathy Decompensated

Emergency department Emergency medicine

diagnostic tools“>Introduction and purpose

hypertrophic cardiomyopathy is a cardiac muscle disorder caused by autosomal dominant mutations of 11 or more genes encoding for cardiac sarcomeric proteins [1-3]. The structural consequence of these mutations is formation of asymmetrical septal wall hypertrophy without ventricle dilation [4]. According to a study conducted by Maron et al. (1995), 1 in 500 adults in the United States have these mu- tations [5,6]. A majority of these cases are diagnosed by providers in larger metropolitan healthcare facilities [3,7,8]. Less frequently is it seen among older patient populations in community hospital emer- gency department (ED) settings [7]. The National Heart, Lung, and Blood Institute (NHLBI) has deemed HCM as an unmet-need disease state due to a marked lack of original Randomized controlled trials examining the pharmacological agents used for acute and chronic management of HCM [3].

A literature search using MeSH terms that included hypertrophic cardiomyopathy, emergency department, and pharmacotherapy yielded 64 hits, which revealed that many of the articles were written for cardiologists focusing on surgical interventions to improve long- term outcomes. A limited number of recently published articles exist that describe pharmacological management of acute HCM

* Corresponding author at: Emergency Medicine, Providence St. Peter Hospital, 413 Lilly Rd NE, Olympia, WA 98506, United States of America.

E-mail addresses: [email protected] (M. Gardner), [email protected] (V. Nair), [email protected] (D. Hu).

decompensation, and those that do are aimed at cardiologists practicing in large academic medical centers [9-11].

Clinical presentation of HCM exacerbation in the ED may have a di- verse array of non-specific symptoms such as syncope, hypotension, chest pain, shortness of breath, arrhythmias, heart failure and in worst cases, sudden cardiac death. Many of these patients may not have a his- tory of HCM, which makes the diagnosis critical in appropriately treating these patients.

Resources for ED personnel who manage patients with HCM who present with acute decompensation in the emergency setting are lim- ited. This article aims to fill this knowledge gap through a discussion of diagnostic tools and commonly used pharmacological agents to man- age acute decompensation of HCM in the ED setting.

ED diagnostic tools

The primary tool for diagnosing HCM in the ED is through subjective evaluation of a thorough history intake which includes determinants such as family history of a relative with sudden cardiac death at a young age or early cardiac disease. ED physicians should be aware of symptoms such as near syncope, syncope and chest pain that could be concerning for HCM. An EKG is another diagnostic tool for identifying HCM, and is readily available in all emergency departments [12]. Most patients with HCM will have an abnormal EKG even if there is a normal echocardiogram. The changes on EKG vary depending on the extent of cardiomyopathy. The most frequent findings are secondary to the left ventricular hypertrophy marked by large amplitude QRS. A deep narrow Q wave can also be observed in inferior and lateral leads when septal hypertrophy is present [12]. These findings could mimic myocardial in- farction and may confound the examination in a patient also complaining of chest pain. However, the Q wave in HCM is narrow and deep, whereas in ischemia it is at least 1 mm wide. This narrow and deep Q wave, particularly in the lateral leads (I, aVL, V5 and V6) are the most specific findings in HCM and should prompt the emer- gency physician to consider HCM [12-14].

Although most emergency physicians would like access to formal Echocardiograms, rarely is this possible on an emergent basis. However, Point of Care Ultrasound by the Emergency Physician is a growing tool to help with emergent decision making. This focused echocardiography is a goal directed evaluation to answer a specific clinical question rather

https://doi.org/10.1016/j.ajem.2018.09.003

0735-6757/(C) 2018

Pharmacological management“>M. Gardner et al. / American Journal of Emergency Medicine 36 (2018) 22862288 2287

than identify all possible cardiac pathology [15,16]. Primary indications for using focused echocardiography to evaluate for possible HCM in- clude cardiac arrest, unexplained hypotension, estimation of central ve- nous pressure, and assessment of left ventricular function. Studies show that emergency physicians can accurately estimate left ventricular func- tion, especially when left ventricular dysfunction is severe [15]. Echo- cardiography is the preferred first-line test for symptoms that may represent previously unknown left ventricular failure, and this includes the ability to identify concentric or asymmetric ventricular hypertro- phy. The parasternal long view clearly shows the outflow tract, and asymmetric septal hypertrophy can be identified with a thickened, echogenic LV septum. Concentric hypertrophy is best seen on the apical four-chamber view. In this view, one can identify the symmetrical thick- ening of the left ventricular wall.

Most patients with HCM will be completely asymptomatic until they present with symptoms that are related to left ventricular outflow tract obstruction (LVOT) and diastolic dysfunction. This abnormality pro- duces the nonspecific dyspnea, dizziness, exercise intolerance or syn- cope. Unless a patient has LVOT gradient present, there may not be any Physical exam findings indicative of HCM; therefore, to rule out HCM, physical exam findings should be supplemented by EKG readings that show displaced and hyperdynamic point of maximal impulse (PMI) or double apical impulse during systole, an S4 gallop may be auscul- tated, and there may be a harsh systolic ejection murmur best heard at the apex and radiating to the sternal notch. Unlike most other mur- murs, it can be increased with Valsalva. Unfortunately, patients are often unaware of their problem and completely asymptomatic until they present with sudden cardiac death [12].

Pharmacological management

The goals of treatment are to restore normal sinus rhythm or ven- tricular Rate control [17]. In the setting of hemodynamic instability, con- sider following the ACLS algorithm and performing emergency cardioversion, before continuing to pharmacologic management.

Volume fluctuations impacting preload and/or afterload secondary to diarrhea or other Disease states and medications should be promptly addressed by giving fluid boluses. Hypovolemia may lead to sudden HCM exacerbations, especially in patients with LVOT obstruction. If fluid challenge produces no measurable impact, consider adding pure alpha agonists to maintain afterload.

Due to the impact of afterload on outflow obstruction, pharmacolog- ical agents which decrease preload and afterload (e.g., nitroglycerin) or increase myocardial contractility (e.g., digoxin and beta-agonists) should be avoided [18]. Conversely, agents which preserve or augment afterload will help to decrease the degree of outflow obstruction. Thus, pure alpha-agonists are the preferred vasopressors in patients with HCM and outflow obstruction who experience decompensation [11,19]. Vasopressors with the propensity to increase inotropy such as norepinephrine, dopamine, and dobutamine should be avoided to pre- vent worsening of the demand ischemia.

When diuretics are used for patients with HCM exacerbation and se- vere heart failure, caution must be exercised due to the potential for re- duction in LV preload, because this can exacerbate obstruction and cause hypotension [20].

Sudden drop in preload lowers the stroke volume leading to in- creased inotropy and chronicity to maintain blood pressure, which may lead to chest pain or arrhythmias such as atrial fibrillation [18]. Pharmacological management of new onset atrial fibrillation secondary to HCM decompensation involves rate versus Rhythm control and thromboembolism risk management. There are no randomized control studies comparing clinical outcomes between rate vs rhythm control in acute exacerbations. Beta-blockers or non-dihydropyridine calcium channel blockers (CCBs) alone or in combination, should be used for ventricular rate control [10,21]. It is reasonable to start with a bolus of diltiazem followed by a diltiazem infusion for rate control. Caution

must be exerted when a non-dihydropyridine (CCB) is given for rate control as it may lower afterload, causing re-emergence of arrhythmias and exacerbating LVOT obstruction [20].

If rate control is not successfully achieved through Beta blockers and/or CCBs, amiodarone may be considered for maintenance of sinus rhythm [10,22,23]. There are no studies to date that show that antiar- rhythmic drugs reduce the risk of ventricular arrhythmias. Among the antiarrhythmic agents, sotalol may have a better side effect profile than others, yet it must be used cautiously in patients with moderate to severe hypertrophy. Sotalol has the combined advantageous proper- ties of blocking beta adrenergic receptors and being a class III antiar- rhythmic. In a small double blind, cross-over study of 30 patients, sotalol eliminated supraventricular arrhythmias in 6 out of 7 patients that developed them. It also suppressed ventricular arrhythmias in 7 out of 13 patients [24]. This study however, did not address treating acute arrhythmias in an ED setting. From the limited data and lack of study in an acute setting it is unclear what role sotalol has on treating acute supraventricular and ventricular tachycardia in the ED. In acute onset atrial fibrillation patients with pre-excitation adenosine is contra- indicated due to the risk of developing ventricular tachycardia or ven- tricular fibrillation [17].

Beta blockers are the first line agents used for rate control and HCM symptom management [20,23]. There are approximately 12 clinical tri- als that examine safety and efficacy of beta blockers in HCM, although none of them are true head to head trials [9]. The sympatholytic proper- ties of beta blockers attenuate heart rate, diastolic filling pressure and inotropy, thereby, improving angina, outflow obstruction and shortness of breath [11]. In the setting of hypotension, an esmolol infusion may be considered for rate control, administered concurrently with a pure alpha agonist such as a phenylephrine infusion to maintain afterload.

Non-dihydropyridine calcium channel blockers (CCB) such as verap- amil and diltiazem may also be used as alternatives to beta-blockers for its negative chronotropic and inotropic effects. Verapamil is the better studied CCB than diltiazem that shows improvement in LV diastolic fill- ing pressure, myocardial ischemia, and outflow gradients [23]. The cur- rent guidelines suggest using caution when using the non- dihydropyridine CCBs in patients with severe outflow obstruction due to the potential for afterload reduction from its vasodilatory properties [20]. HCM patients with non-obstructive disease may also experience severe heart failure from compromised systolic function as a late result of the disease. Diltiazem may be utilized as an alternative to Verapamil for symptom relief; however, its utility in management of HCM symp- tom relief has not been studied systematically to date [10]. Another rea- sonable therapy to consider for patients with high outflow gradients who have failed beta-blockers and (or) calcium channel blockers is disopyramide, which is a Vaughan-Williams class IA antiarrhythmic medication that improves outflow gradients at rest due to its capacity to decrease myocardial contractility [20,25]. Cautious monitoring for disopyramide side effects is advised as the risk includes QTc prolonga- tion and anticholinergic side effects [25]. Disopryramide should not be administered in the absence of beta blockers or CCB among HCM pa- tients with atrial fibrillation due to its propensity to increase AV nodal conduction and, therefore, ventricular rate [20].

Conclusion

In the busy community hospital ED settings, the emergency physi- cian must act quickly to intervene and rapidly manage acutely decom- pensating HCM patients. HCM is a complex disease process with a wide variety of presentations. It can easily be missed if the physician does not specifically consider it for the patient with such symptoms as dyspnea, dizziness, palpitations, near syncope or syncope, and exercise intolerance, or shortness of breath with meals or alcohol use. In such sit- uations, the Emergency Department team must consider HCM in the differential for those patients with non-specific symptoms and consider the diagnosis especially when looking at the EKG, as well as consider

2288 M. Gardner et al. / American Journal of Emergency Medicine 36 (2018) 22862288

bedside US which may demonstrate the presence of asymmetric or symmetric hypertrophy. This disease process is currently best managed with medications, and acute exacerbations or decompensation will re- quire specific appropriate cardiovascular pharmacotherapy and modal- ities until a specialist can be involved in the patient’s care. Ultimately, the quick identification of the etiology of the patient’s symptoms and the correct use of pharmacologic interventions will help bridge the pa- tient to definitive cardiologist intervention and management.

Meetings

None.

Grants and other financial support

None.

Conflicts of interest

None to disclose.

Acknowledgments

The authors gratefully acknowledge Dr. John Waggoner and thank him for his contributions as a consultant during the writing of this manuscript.

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