A 64-year-old male applied for life insurance. He has a family history of coronary artery disease in a brother who underwent a coronary artery bypass graft at 58. He has been treated for hypertension and hyperlipidemia. Seven months prior to the application he complained
of progressive chest pain on exertion, typical of angina. A treadmill test lasting 10 minutes was positive for chest pain but negative for ECG changes. A transthoracic echo was within normal limits with a left ventricular ejection fraction of 60%.
A left heart catheterization performed six months prior to application was negative for obstructive lesions but it revealed left anterior descending (LAD) artery myocardial bridging (MB) that showed minimal mid-systolic compression. The LAD was dominant and wrapped around the apex. The posterior descending was a small vessel. Medical therapy was started with beta blockers, a diuretic and aspirin. He was already on statins and an angiotensin converting enzyme inhibitor. At a one-month follow-up of the new treatment regiment, he was asymptomatic.
What is a myocardial bridging and what are the mortality implications?
Myocardial bridging (MB), first described anatomically by Reyman in 1737, is a congenital variant of a coronary artery in which a portion of an epicardial coronary artery (most frequently the
middle segment of the LAD artery) takes an intramuscular course. This arrangement of a “tunneled” segment of the artery under the “bridge” of overlying myocardium frequently results in vessel compression during systole.
While frequently asymptomatic this condition may be responsible for adverse complications including angina, myocardial ischemia, acute coronary syndromes, left ventricular stunning or dysfunction, arrhythmias or even sudden cardiac death.
The physiological characteristics and morphological consequences of MB are still not yet fully understood, even though there have been many studies specifically analyzing these issues. There are two core mechanisms through which MB is thought to cause myocardial ischemia and myocardial infarction (MI) – the development of atherosclerosis proximally from the bridged
segment and a direct compression of the coronary artery by the MB. In subjects with MI, the thickness of the MB is on average greater compared to the ones found in subjects without MI.
It was usually considered a benign condition mostly because it constricts the bridged coronary during systole, while most of the myocardial blood perfusion occurs during diastole. Even if MB
mainly causes a systolic narrowing of the affected coronary, both cardiac phases are affected.
Recently, it has been recognized that myocardial ischemia is not purely related to systolic vascular compression. Indeed, systolic vessel compression has been shown to persist into mid-to-late diastole. The hemodynamic disturbance imposed by this persistent diastolic luminal narrowing was corroborated by increases in both average peak flow velocity and average diastolic peak flow velocity, with only minor changes in systolic blood flow within the bridged
segment of the coronary artery. These data suggest that both systolic and diastolic flow impairment contribute to myocardial supply-demand mismatch in patients with myocardial bridging.
Moreover, during left ventricular systole, this segment of the vessel is compressed, a condition referred to as “milking”. Myocardial bridge “milking” might also cause ischemia by “intramural steal” or “branch steal” mechanism, which are linked to decreased perfusion pressure of septal branches and blood suction.
“Milking Effect” in Coronary Angiography. (A) Systolic compression of myocardial bridges: the “milking effect.” (B) Subsequent increase in vessel lumen diameter during diastole. White arrows indicate areas of myocardial bridging.
Source: MT Corban et al J Am Coll Cardiol 2014;63:2346–55
Autopsy and intravascular ultrasound studies have shown that the intramural and distal segments of bridged vessels remain free from atherosclerotic disease while the proximal segment of the vessel is prone to developing atherosclerosis. Biomechanical forces may explain these observations.
Autopsy studies have shown that coronary segments immediately proximal to myocardial bridges, where wall shear stress (WSS) is low, have structurally dysfunctional, flat and polygonal endothelial cells. Endothelial cells lining bridged segments where WSS is physiological or high are structurally intact. Clinical studies in patients with mild atherosclerosis without bridging have shown greater plaque progression in segments with low WSS compared with physiological or high WSS.
There is some confusion whether myocardial bridges constitute an anomaly or a normal variation. The prevalence of myocardial bridging varies between 0.15% to 25% angiographically and 5% to 86% at autopsy with a mean of 25%.
The angiographic detection rate of MBs can be increased to 40% with provocative tests or intracoronary injection of nitroglycerin. A higher prevalence has been observed in patients with hypertrophic cardiomyopathy and in recipients of cardiac transplants.
The difference in prevalence when estimated by these modalities reflects the fact that angiographic evidence of myocardial bridging depends upon a variety of factors, including
- the thickness of the myocardium
- the length of the bridged segment
- the orientation of the coronary artery to the myocardial fibers
- the nature of the tissue interposed between the coronary artery and the myocardium
- the observer’s experience
- the intensity with which bridging is sought.
It is likely that bridging often goes unrecognized on angiography. Myocardial bridges can be found in any epicardial artery, with 67% to 98% occurring in the LAD.
In most patients myocardial bridging is asymptomatic. Symptomatic patients may present with clinical manifestations of myocardial ischemia that are like those in patients with fixed
obstructive coronary artery disease such as an acute coronary syndrome, coronary spasm, exercise-induced dysrhythmias, atrioventricular conduction block, myocardial stunning, transient
ventricular dysfunction, syncope or sudden death.
Coronary cineangiography remains the most common technique for diagnosing myocardial bridging. The typical description of bridging on angiography involves a systolic narrowing or
“milking” of an epicardial artery, with a “step-down” and “step-up” demarcating the impacted area.
Intracoronary Doppler Doppler-tipped guidewires allow accurate measurement of intracoronary flow velocity for the first time. Using doppler on 47 interrogations of myocardial bridges revealed a characteristic “spike-and-dome” pattern or “fingertip” phenomenon with abrupt early diastolic flow acceleration, rapid mid-diastolic flow deceleration and a mid-to-late diastolic plateau.
Retrograde flow during the systolic period can be detected immediately proximal to the bridged segment exacerbated by nitroglycerin provocation, especially in deep bridges. In addition, coronary flow reserve in these patients is impaired distal to the bridge, with a mean of 2.0 (normal >3.0), despite being normal or mildly reduced (mean 2.7) proximal to the bridge.
Intravascular ultrasound (IVUS) On IVUS, the tunneled segment of an artery clearly demonstrates systolic compression (which can be either eccentric or concentric) that persists into diastole. There is also a highly specific echolucent “half-moon” appearance
throughout the cardiac cycle, the etiology of which is not well understood.
Fractional flow reserve (FFR) FFR assessment has proven to be an important tool in the physiologic assessment of myocardial bridges. Hemodynamic alteration due to the myocardial bridging manifested most prominently in a decrease in diastolic FFR (0.88 down to 0.77), whereas mean FFR decreased to a lesser extent (0.90 down to 0.84). It is thought that mean FFR measurements are artifactually elevated by overshooting of systolic pressures and
thus diastolic FFR evaluation should be the technique of choice.
Cardiac computed tomography angiography (CCTA) CCTA has become a valuable tool in the analysis of coronary anatomy and patency. Studies using CT to evaluate myocardial bridging have detected intramyocardial segments at much higher rates than by angiography. CT-based non-invasive FFR measurement may yet prove useful as a method for combined anatomical/hemodynamic study of myocardial bridges, but such an application has not yet
been reported in the literature.
Most instances of bridging have no clinical significance. However, severe bridging of the major coronary arteries can produce myocardial ischemia, coronary thrombosis, myocardial infarction
and stress cardiomyopathy.
Some previously asymptomatic individuals may become symptomatic. Pathophysiologic factors that may unmask or exacerbate myocardial bridges are a patient’s age, heart rate,
left ventricular hypertrophy and the presence of coronary atherosclerosis. All of these may worsen the supply-demand mismatch imposed by the bridge, reducing coronary reserve.
Medical therapy appears to be the treatment of choice for the vast majority of patients with MB in the absence of randomized trials comparing optimal medical treatment versus percutaneous
coronary intervention with drug-eluting stents.
Beta-blockers are considered first-line therapy because of their negative chronotropic and inotropic effects and because of the reduction in sympathetic drive (exertion or stress-induced).
Calcium-channel blockers may offer additional benefit by reducing concomitant vasospasm. Ivabradine, by reduction of the heart rate via specific inhibition of If ion channels, might be considered in place of or together with a lower dose of beta-blockers and calcium-channel blockers.
Aggressive risk factor modification is recommended due to the inherent risk of the MB inducing atherosclerosis. Antiplatelet therapy should be considered when subclinical atherosclerosis is
Pure vasodilators such as nitroglycerin are not indicated because they can worsen symptoms due to the increased systolic compression of the tunneled artery, tachycardia and proximal
vessel dilation, all of which may aggravate the flow reversal in the proximal coronary segment to MB.
Patients who are refractory to maximal medical treatment may benefit from other therapeutic approaches including stents, minimally invasive coronary artery bypass grafting or surgical
R. Rubinshtein et al explored the relation between the presence of isolated MB (no prior history of coronary artery disease) and subsequent adverse cardiac events in symptomatic patients
referred for coronary computed tomography angiography (CCTA). Outcomes were compared between patients with MB versus those without MB using the Cox models. They did not find a significant association between MB on CCTA and increased risk for CV death or MI during six years of follow-up.
Survival free of CV death or non-fatal MI in relation to the presence of MB among 334 patients with chest pain but without obstructive CAD.
Source: European Heart Journal – Cardiovascular Imaging (2013) 14, 579–585
The data about CV death and MI were confirmed by S. Hostiuc et al in a recent meta-analysis of 21 relevant studies. Nonetheless they showed an association between MB and an increased risk
of major cardiovascular events (MACE) OR=1.52 and myocardial ischemia OR=3.0.
Returning to the case
Recent non-invasive coronary imaging tests such as CCTA identify myocardial bridging as a common finding, apparently conveying a benign prognosis in most patients. In the case of this 64-year-old applicant without obstructive lesions of coronary arteries by angiography, there was no objective sign of myocardial ischemia, but he was symptomatic, showing there is slightly greater suspicion of hemodynamic effects of MB. With proper medical treatment he is now asymptomatic, and we anticipate a low to low-moderate extra mortality risk.
JDS Sara et al The Prevalence of Myocardial Bridging Associated with Coronary Endothelial Dysfunction in Patients with Chest Pain and Non-Obstructive Coronary Artery Disease. EuroIntervention 2019; Jaa-506 2019, doi: 10.4244/EIJ-D-18-00920
R.Rubinshtein et al Long-term Prognosis and Outcome in Patients with a Chest Pain Syndrome and Myocardial Bridging: a 64-slice Coronary Computed Tomography Angiography Study European Heart Journal – Cardiovascular Imaging (2013) 14, 579–585.
P.Sorajja et al Myocardial Bridging of the Coronary Arteries Uptodate (last accessed 05/10/2019).
S.M Yuan et al Myocardial Bridging Braz J Cardiovasc Surg 2016;31(1):60-2.
AG Monroy-Gonzalez Myocardial Bridging of the Left Anterior Descending Coronary Artery Associated with Reduced Myocardial Perfusion Reserve: a 13N-ammonia PET Study The International Journal of Cardiovascular Imaging (2019) 35:375–382.
S. Hostiuc Cardiovascular Consequences of Myocardial Bridging: A Meta-Analysis and Meta-Regression Scientific Reports | 7: 14644 | DOI:10.1038/s41598-017-13958-0
MT Corban et al Myocardial Bridging Contemporary Understanding of Pathophysiology with Implications for Diagnostic and Therapeutic Strategies JACC 2014;63:2346–55.
G. Tarantini et al Left Anterior Descending Artery Myocardial Bridging A Clinical Approach JACC 2016;68:2887-99.
Lozano et al Long-Term Prognosis of Patients with Myocardial Bridge and Angiographic Milking of the Left Anterior Descending Coronary Artery Rev Esp Cardiol 2002;55(4):359-64.