Myocardial Bridging in the Setting of Dilated Myocardiopathy

Summary 

Myocardial bridging is a congenital coronary anomaly usually found incidentally on autopsy. Less frequently, it becomes functionally important and can be identified in coronary angiography as a narrowing of the coronary arteries, involving mostly the left anterior descending coronary artery (LAD). The bridging effect occurs during systole, producing the “milking” sign of the vessel, followed by a complete or partial decompression during diastole. Although myocardial bridges can be found in 40-80% of autopsies, in only 0.5-16% of the cases does it present with functional consequences. Severity and clinical manifestations vary significantly. We report the case of a Hispanic male who presented with acute chest pain, dyspnea, and a decrease in functional capacity of about two weeks duration. Due to suspicion of acute coronary syndrome, the patient underwent percutaneous coronary angiography that identified an extensive coronary bridge crossing over the LAD. Echocardiogram showed a moderately dilated left ventricle with severely reduced systolic function. We consider this presentation of interest due to the unusually severe myocardial bridging of the LAD in the setting of dilated myocardiopathy. This case also represents the therapeutic challenges associated with bridging, revealing the need for larger randomized, clinical trials that will allow physicians to move beyond empiric treatment to more individualized strategies.

Introduction 

Myocardial bridge (MB) is a congenital anatomic variant that occurs when one of the coronary arteries tunnels through the myocardium instead of having a normal epicardial course.¹ MB may essentially involve any epicardial artery, but the LAD is affected in almost 80% of cases.² MB is considered a benign condition often discovered incidentally in necropsy series. It is present in almost one-third of the adult population.³ 

Functional bridging is, fortunately, significantly less frequent. When using an angiographic approach, the detection rate is estimated to be about 16%. This detection rate increases up to almost 40% if provocative tests such as the administration of intracoronary nitroglycerin are used.⁴ The typical “milking” and “step down-step up” effects indicating the narrowing of the coronary artery during systole are shown by use of coronary angiography. Nevertheless, other modalities can be used for diagnosis, including intravascular ultrasound, multi-slice computed tomography, single-photon emission computed tomography, and/or contrast stress echocardiography.⁵ 

The clinical importance of MB remains questionable, since physiological systolic transient constriction of the coronary arteries theoretically should not affect the myocardial perfusion that mostly occurs during diastole. Recent data, however, has evidenced that the systolic vessel compression may persist until mid-to-late diastole, suggesting that both systolic and diastolic flow impairment may have a role in the functional consequences associated with MB.⁶ The hemodynamic impact of MB depends of several factors, including (a) the length and thickness of the tunneled segment, (b) the orientation between the myocardial fibers and the bridge itself, (c) the presence of adipose tissue around the bridge, as well as (d) the intrinsic tone and presence of baseline fixed narrowing of the coronary arteries.⁷ 

Although myocardial bridging is typically benign and is found incidentally, it is important to recognize both pathophysiological and clinical factors that may aggravate it, and identify undesirable outcomes in a previously asymptomatic patient with congenital myocardial bridging. Increasing age, coronary atherosclerosis, hypertension, and left ventricular hypertrophy can magnify the functional effects of the bridging. Other anatomic variables such as the depth (>1 or >2 mm) and length of the entrapped artery are equally important in determining the presence or absence of symptoms. The consequences of a partially tunneled artery versus a very thick myocardial bridge associated with myocardial hypertrophy⁸ are completely different. 

The clinical presentations of MB are highly variable, ranging from totally asymptomatic patients to exercise-induced symptoms, acute coronary syndromes, coronary spasms, transient ventricular dysfunction, Takotsubo syndrome or even life-threatening ventricular arrhythmias, and in the worst case scenario, sudden cardiac death.⁹ 

Case Description 

We describe the case of a 64-year-old Hispanic male construction worker with chest pain. Substernal chest tightness of almost two weeks’ duration, dyspnea, dyspnea on exertion, episodes of nocturnal paroxysmal dyspnea, and orthopnea were all present and had impacted his daily activities. He was an ex-smoker, but active alcohol drinker. He had vitiligo and a recurrent upper respiratory tract infection over a period of two months for which he was treated with antibiotics and steroids in the ambulatory setting by his primary care physician, with no resolution of symptoms. He reported no family history of coronary artery disease or cardiomyopathies. 

At admission, vital signs were stable, and a grade 3/6 systolic rumbling murmur consistent with mitral regurgitation was heard in point of maximal impulse. The patient’s initial troponin-T concentration was 0.00 ng/ml with elevated B-type natriuretic peptide concentration of 755 pg/ml. A chest x-ray demonstrated cardiomegaly and the electrocardiogram showed sinus rhythm with premature ventricular complexes, left ventricular hypertrophy with QRS widening, and repolarization abnormalities. No previous electrocardiogram was available for comparison. Bedside echocardiogram showed a moderately dilated left ventricle with severely reduced systolic function and ejection fraction of 20%, grade II diastolic dysfunction, moderate mitral valve regurgitation, and mildly reduced right ventricle systolic function (Videos 1A and 1B). 

Based on the suspicion of acute coronary syndrome, the patient was urgently transferred to the cardiac catheterization laboratory. Coronary angiography was performed using right radial artery access. There were no significant lesions in the left main, left circumflex, obtuse marginal branch, or right coronary arteries, but there was severe compression/bridging of the middle LAD (Figures 1-3, Videos 2A and 2B). 

The patient remained asymptomatic during the course of hospitalization, but with low blood pressure. A decision was made to perform functional studies in order to fully address the hemodynamic effects of the MB and possible necessity of an invasive surgical approach. The patient underwent a Rubidium positron emission tomography myocardial rest and stress scan. Results revealed a small focus of mild severity stress-induced ischemia in the distal medial wall of the left ventricle with global hypokinesia and reduced ejection fraction, and a small and old inferoseptal apical infarct. 

Based on the absence of symptoms and low-risk results derived from the stress test, there was careful consideration of surgical intervention, but after a detailed discussion with the patient and family, it was decided to initiate conservative medical treatment and close follow-up. Treatment with the funny channel blocker, ivabradine (Corlanor, Amgen), was started with excellent tolerance to date and resolution of chest pain. 

Discussion 

The myocardial bridging phenomena was first reported in 1737 and a detailed analysis of autopsies series was presented 200 years later.¹⁰ Of interest, myocardial bridges represent an anomaly of the normal heart anatomy, reflecting an evolutionary vestige of the genetic code. While most of the major vessels are located within the myocardium in rodents, tunneled vessels are rare among horses or pigs.¹¹ Myocardial bridging can be identified angiographically by appreciating the narrowing or “milking” effect of the major coronary arteries in their unexpected intramyocardial course during systole. The dynamic nature of the reversible obstruction of the coronary arteries affected by bridging (mostly the LAD) is used to differentiate whether the origin of the symptoms, if present, are MB or fixed obstruction. Myocardial bridging is usually silent, the reason why it is mostly found incidentally in autopsies. Nevertheless, it can also become functionally active with highly variable clinical manifestations, ranging from myocardial ischemia to acute myocardial infarction or even sudden death.¹²

A therapeutic approach to myocardial bridging may be challenging due to different factors. The wide range of clinical manifestations, the concomitant presence of other heart disorders that can act as confounding factors in the pathophysiology of the patient’s symptoms, and finally, the lack of official guidelines that define a clear-cut classification of the different types of myocardial bridging may all explain the absence of specific protocols of action once the myocardial bridge phenomena is diagnosed. Pharmacological therapy is established as the first line of treatment and includes beta-blockers (negative chronotropic and inotropic effect) and calcium channel blockers (reduction of vasospasm).¹³ Pure vasodilators such as nitroglycerin, however, are contraindicated in this scenario, due to the increased reflex sympathetic stimulation of contractibility, and worsening of symptomatology.¹⁴

Ivabradine (Corlanor, Amgen) is a cardiotonic agent that provides selective inhibition of the funny channels (If) located in the sinoatrial (SA) node, resulting in the disruption of the flow of the If ion, resulting in the slowing of the SA node firing, and reducing the heart rate by prolonging diastolic depolarization.¹⁵ This agent is an alternative to treatments such as beta-blockers or calcium channel blockers in the management of heart failure when the patients can’t tolerate the hemodynamic effects of these agents. Also, it can be used off-label in inappropriate sinus tachycardia and stable angina. By the same concept, ivabradine has a role in treatment of myocardial bridging in addition to, or instead of, the first lines of medical therapy when patient’s hemodynamics are incompatible with use of beta-blockers or calcium channel blockers. 

More invasive strategies have been implemented in the treatment of myocardial bridging as well. Percutaneous intervention with stent implantation in symptomatic patients, as well as surgical approaches such as coronary artery bypass grafting or myotomy, have been studied.^16-18 Results appear to be conflicting, mostly due to limited available data and lack of randomized clinical trials comparing different types of invasive strategies. Medical therapy currently is the mainstay of treatment. Invasive intervention is reserved for patients who remain symptomatic, despite optimal pharmacological treatment. 

The case that we present can be challenging due to the presence of confounding factors that may play a role in the development of our patient’s symptoms. In fact, several questions derived from our case may deserve further discussion. Is the myocardial bridging by itself responsible for our patient’s symptoms? Was the degree of compression affecting the LAD a good enough reason to bypass the first-line medical treatment and proceed directly with a more invasive approach? In other words, does the unclear role of the bridging phenomena in our patient’s symptoms justify the delay in surgical therapy, even though there is always a risk of potential sudden cardiac death in this patient? 

Conclusion 

There is growing body of knowledge on myocardial bridging, but the heterogeneity in terms of therapeutic approach is still a concern. Large, randomized, clinical trials are clearly needed in order to centralize databases and to allow better analysis of the outcomes associated with diverse therapeutic approaches. Such studies with longer follow-ups will allow us to move beyond the current empiric treatment to more individualized strategies for patients affected by this potentially fatal congenital condition.

References 

1. Alegria JR, Herrmann J, Holmes DR Jr, et al. Myocardial bridging. Eur Heart J. 2005 Jun; 26(12): 1159-1168. 
2. Loukas M, Curry B, Bowers M, Louis RG Jr, Bartczak A, Kiedrowski M, Kamionek M, Fudalej M, Wagner T. The relationship of myocardial bridges to coronary artery dominance in the adult human heart. J Anat. 2006 Jul; 209(1): 43-50. 
3. Möhlenkamp S, Hort W, Ge J, Erbel R. Update on myocardial bridging. Circulation. 2002 Nov 12; 106(20): 2616-2622. 
4. Lee MS, Chen CHJ. Myocardial bridging: an up-to-date review. J Invasive Cardiol. 2015 Nov; 27(11): 521-528. 
5. Gawor R, Kuśmierek J, Płachcińska A, et al. Myocardial perfusion GSPECT imaging in patients with myocardial bridging. J Nucl Cardiol. 2011 Dec; 18(6): 1059-1065. 
6. Bourassa MG, Butnaru A, Lespérance J, Tardif JC. Symptomatic myocardial bridges: overview of ischemic mechanisms and current diagnostic and treatment strategies. J Am Coll Cardiol. 2003 Feb 5; 41(3): 351-359. 
7. Gould KL, Johnson NP. Myocardial bridges: lessons in clinical coronary pathophysiology. JACC Cardiovasc Imaging. 2015 Jun; 8(6): 705-709. 
8. Kim PJ, Hur G, Kim SY, et al. Frequency of myocardial bridges and dynamic compression of epicardial coronary arteries: a comparison between computed tomography and invasive coronary angiography. Circulation. 2009 Mar 17; 119(10):1408-1416. 
9. Feld H, Guadanino V, Hollander G, et al. Exercise-induced ventricular tachycardia in association with a myocardial bridge. Chest. 1991 May; 99(5):1295-1296. 
10. Reyman HC. Disertatio de vasis cordis propriis. Med Diss Univ Göttingen. 7th Sept 1737; 1-32. 
11. Poláek P, Zechmeister A. The occurrence and significance of myocardial bridges and loops on coronary arteries. In: Krutna, V ed. Monograph 36: Opuscola Cardiologica. Brno, Czech Republic: Acta Facultatis Medicae Universitatis Brunenses, University J. E. Purkinje; 1968:1-99. 
12. Morales AR, Romanelli R, Boucek RJ. The mural left anterior descending coronary artery, strenuous exercise and sudden death. Circulation. 1980 Aug; 62(2): 230-237. 
13. Schwarz ER, Gupta R, Haager PK, et al. Myocardial bridging in absence of coronary artery disease: proposal of a new classification based on clinical angiographic data and long-term follow-up. Cardiology. 2009; 112(1): 13-21. 
14. Hongo Y, Tada H, Ito K, et al. Augmentation of vessel squeezing at coronary-myocardial bridge by nitroglycerin: study by quantitative coronary angiography and intravascular ultrasound. Am Heart J. 1999 Aug; 138(2 Pt 1): 345-350. 
15. Borer JS, Böhm M, Ford I, et al; SHIFT Investigators. Effect of ivabradine on recurrent hospitalization for worsening heart failure in patients with chronic systolic heart failure: the SHIFT Study. Eur Heart J. 2012 Nov; 33(22): 2813-2820. 
16. Ernst A, Bulum J, Šeparović Hanževački J, et al. Five-year angiographic and clinical follow-up of patients with drug-eluting stent implantation for symptomatic myocardial bridging in absence of coronary atherosclerotic disease. J Invasive Cardiol. 2013 Nov; 25(11): 586-592. 
17. Sun X, Chen H, Xia L, et al. Coronary artery bypass grafting for myocardial bridges of the left anterior descending artery. J Card Surg. 2012 Jul; 27(4): 405-407. 
18. Iversen S, Hake U, Mayer E, et al. Surgical treatment of myocardial bridging causing coronary artery obstruction. Scand J Thorac Cardiovasc Surg. 1992; 26(2): 107-111. 

¹Division of Internal Medicine, Graduate Medical Education, MountainView Hospital, University of Nevada, Reno, Nevada; ²Division of Cardiology and Interventional Cardiology, MountainView Hospital, Las Vegas, Nevada

Disclosures: The authors report no conflicts of interest regarding the content herein. 

The authors can be contacted via Navid Kazemi, MD, FACC, Chief of Division of Cardiology and Interventional Cardiology, at navidka@cox.net.