A 48-year-old woman presented to the cardiology clinic with 1 month of worsening symptoms and declared, “I have had chest pain for 40 years.” She recalls having spontaneous episodes of intermittent squeezing chest pain as a child that lasted 5 to 10 seconds in duration. Results of a pediatric workup were unrevealing and thought to be “growing pains.” However, the episodes continued into adulthood and past the births of two children. The chest pain occurred primarily at rest, at times accompanied by palpitations, without a clear trigger, and was not exacerbated by exercise. Over the past month the frequency of the symptoms has increased, and in one case lasted 15 minutes before subsiding. She has a history of attention deficit disorder for which she is intermittently treated with methylphenidate. Her cardiac symptoms preceded its use. She does not use illicit substances, and has a father who required a valve replacement.

Outpatient workup was initiated. An electrocardiogram (ECG) showed no accessory pathways or infarction; results of a 24-hour ambulatory ECG were unrevealing, and results of a transthoracic echocardiogram were unremarkable, notably without hypertrophy or mitral valve disease. She exercised 8.8 minutes and 10.1 METS on an exercise treadmill with no ischemic changes. Basic laboratory values were normal, with the exception of elevated cholesterol and C-reactive protein levels. She returned to the clinic complaining of persistent symptoms, and additional studies were ordered. A computed tomography coronary angiogram (CTCA) revealed a 3-cm long myocardial bridge (MB) in the mid-left anterior descending artery (LAD) without concomitant atherosclerotic plaque (Figure 1). Additionally, the mid-right coronary artery was intracavitary, traversing the right atrium (Figure 2). Exercise single-photon emission computed tomography (SPECT) demonstrated no defects, and magnetic resonance imaging (MRI) revealed no perfusion defects or scars. Given the lack of physiologic significance to the bridge, reassurance was provided to the patient; additional workup in the form of invasive intracoronary Doppler measurement with vasoreactivity testing to exclude vasospasm or microvascular disease was not pursued.

Discussion

MB is found in an unexpectedly large number of patients with angina without obstructive coronary artery disease, but their significance and the efficacy of treatment are not well established.¹ Patients typically present with angina, syncope, or other symptoms of myocardial ischemia (Table 1), and MB should be especially considered in patients at low risk for atherosclerosis.² MB is a congenital abnormality defined as an intramyocardial route of an epicardial coronary artery, and its prevalence varies by diagnostic modality. Coronary angiography, which has historically been the diagnostic standard, detects bridges in < 5% of cases, and has been outpaced by more sensitive modalities that more closely detect their prevalence in the general population, which is upwards of 86% as found by autopsy studies.³ CTCA studies report a 5.7% to 58% prevalence.⁴ The increased prevalence found by autopsy or CTCA can be attributed to anatomic evaluation of the bridge versus detection of systolic compression by coronary angiography, indicating that most bridges do not impact coronary perfusion. Anatomic positioning is almost always in the mid-LAD but can be found on any epicardial artery.⁵ Their prevalence is generally understood to be increased in patients with hypertrophic cardiomyopathy, with a 41% prevalence, although whether their presence increases the risk of cardiac death in this high-risk population has not been established.^6,7

The pathophysiology of ischemia is classically attributed to systolic compression of the tunneled artery, although numerous studies have shown vessel compression extending into diastole causing increased flow velocities and reduced flow reserve.^8-10 These hemodynamic effects may lead to endothelial damage, coronary vasospasm, and acute coronary syndrome.¹¹ Degree of ischemia may also depend on the location, thickness, and length of the muscular bridge.¹² Concomitant atherosclerosis proximal to the bridge due to hemodynamic disruptions occur in greater frequency, and an elevated C-reactive protein level may be an indicator of its development.^8,10,13 Endothelial analysis at the proximal location showed structurally dysfunctional endothelial cells with a low shear stress state, allowing increased vascular expression for plaque development.^14,15 In contrast, the tunneled segment of the artery is protected from atherosclerosis with structurally intact endothelium, laminar flow, and high shear.¹⁴ Although most cases are benign, MB has been associated with clinical complications such as arrhythmia, coronary vasospasm, acute coronary syndromes, depressed left ventricular function, myocardial stunning, early death after cardiac transplantation, and sudden death.^16,17 It is still debated whether MB is the direct cause of these adverse events.¹⁸

Numerous imaging modalities can be used in the diagnosis of MB. Although coronary angiography has been historically used, CTCA shows promise as a noninvasive diagnostic tool, providing anatomic visualization of depth, length, and precise location of the tunneled artery.^10,12 Deep MBs on CTCA have been found to be more greatly associated with mechanisms of ischemia, whereas superficial bridges are more often benign. Deep bridging is defined as > 2 mm of myocardial enclosure of the artery, and superficial bridging is defined as incomplete or < 2 mm depth of myocardial enclosure.¹⁹ Cardiac MRI is another noninvasive technique for visualization and functional assessment of MB.^20,21 ECG, stress echocardiogram, SPECT, and positron emission tomography (PET) can be useful in the differential diagnosis for myocardial ischemia, and provide an alternative to intracoronary testing for the presence of functional ischemia in patients with MB. Exercise and dobutamine are preferred for stress testing.^22-24 Patients with MB have a higher prevalence of a positive exercise ECG result,^19,25 and septal wall abnormalities on stress echocardiogram have been shown to correlate with the presence of LAD bridges, a manifestation of increased velocity and decreased perfusion at the tunneled region of ischemia.²⁶ Although stress imaging can provide useful physiologic information, its sensitivity and specificity for hemodynamically significant MB is incomplete and not fully established.^23,24

In addition to coronary angiography, supplemental intracoronary diagnostic modalities include intravascular ultrasound (IVUS), intracoronary Doppler, and diastolic fractional flow reserve (FFR). Identification of systolic compression or an echolucent half-moon sign on IVUS confirms bridging.¹ Diagnosis by intracoronary Doppler depends on identification of the characteristic early diastolic “fingertip” phenomenon, reduced systolic antegrade flow, decreased diastolic/systolic velocity ratio, and retrograde flow into the proximal segment.¹⁰ Additionally, diastolic FFR < 0.75 is an important measure of the hemodynamic significance of MB, indicating its association to ischemia.¹⁰ Noninvasive and intracoronary diagnostic modalities are summarized in Table 2.

The mainstay of treatment for symptomatic MB includes β-blockers and nondihydropyridine calcium channel blockers to relieve hemodynamic disturbances and the effects of coronary vasospasm. In contrast, nitrates should be used with caution due to reflex tachycardia that exacerbates ischemia from bridging.^27-29 When symptoms sustain despite medical therapy, surgical options for treatment involve myotomy, resection of the overlying myocardium, or coronary artery bypass graft (CABG) surgery. Although both procedures have been shown to be comparable by clinical success, myotomy may be preferred for patients with substantial risk for myocardial infarction, ventricular tachycardia, or significant systolic compression. However, these surgical techniques have not been directly compared.³⁰ Cases with deep or extensive MB likely favor CABG to eliminate the risk for ventricular perforation in myotomy. Percutaneous coronary intervention (PCI) has also been shown to resolve symptoms secondary to MB; however, there are numerous reports of coronary perforation and stent fraction, and reported rates of in-stent restenosis are suboptimal, although drug-eluting stents have reduced in-stent restenosis rates compared with bare-metal stents in this patient cohort.³¹ It is important to note that studies are lacking in the use of second-generation drug-eluting stents for treatment of bridges. Suggested steps in diagnosis and treatment of MB as informed by current literature and the Schwarz classification for MB and treatment are summarized in Table 3.^10,29

Anatomic MB is prevalent in a large proportion of the general population and is increasingly identified by CTCA. Although the presence of a MB may account for some patients with angina without obstructive coronary artery disease, even in the absence of physiologic bridging, significant detectable ischemia is far less common as assessed by intracoronary and noninvasive diagnostic modalities such as intracoronary pressure wires and various forms of stress testing, and the vast majority are benign requiring only reassurance to the patient.²² β-blockers and nondihydropyridine calcium channel blockers are the primary treatment options; surgical myomectomy, CABG, and PCI are reserved for patients with demonstrable ischemia caused by bridging who are refractory to medical therapy. Recent advances in noninvasive imaging have both increased our appreciation of the prevalence of anatomic bridges and allowed us to assess for physiologic significance outside of the cardiac catheterization laboratory, but studies are needed to directly compare imaging modalities for their ability to detect ischemia in bridging. The arrival of CTCA fractional flow reserve and proliferation of hybrid PET and CT or MRI systems with intravenous contrast may also allow for noninvasive simultaneous anatomic and physiologic assessment of MB. Studies are needed to compare surgical myomectomy with CABG, and outcomes for PCI of bridges with second-generation drug-eluting stents are needed. 

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