Unexplained Syncope in Athletes

Abstract

Evaluation of syncope in athletes can be challenging, with a vast array of potential explanations ranging from vasovagal to ventricular arrhythmias secondary to an arrhythmogenic cardiomyopathy. The evaluation of syncope requires a thorough history and physical examination, electrocardiogram, and in many cases further diagnostic testing and imaging including stress testing, transthoracic echocardiography, and cardiac magnetic resonance imaging. In this case series, we report 4 cases of previously unexplained syncope in athletes of various levels, with the underlying mechanism of left ventricular outflow tract obstruction (LVOTO). Our findings indicate that LVOTO can cause syncope with or without the presence of significant left ventricular hypertrophy. These cases demonstrate the utility of stress transthoracic echocardiography in eliciting LVOTO and how detecting LVOTO can drastically change clinical management for athletes, especially with respect to implantable cardioverter-defibrillator placement.

Visual Summary

The evaluation of syncope in an athlete can be challenging, as etiologies may be as benign as vasovagal syncope or a harbinger for sudden cardiac death.^1,2 Red flags on history and physical for a cardiac cause include an exertional component to syncope, sudden drop syncope, chest pressure, family history of unexplained cardiac death, and the presence of a murmur.³ An electrocardiogram (ECG) is the first screening test to evaluate for potentially cardiac etiologies such as hypertrophic cardiomyopathy (HCM), arrhythmogenic cardiomyopathy, Wolff-Parkinson-White syndrome, and long QTc syndrome. In many cases, further diagnostic and imaging testing is pursued, including arrhythmia monitors, stress testing, transthoracic echocardiography (TTE), coronary cardiovascular computed tomography angiography, and cardiac magnetic resonance imaging (MRI) to rule out arrythmias, ischemia, anomalous coronary artery, HCM, and other cardiomyopathies.

Take-Home Messages

• •LVOTO should be considered when evaluating athletes with syncope, as the detection of LVOTO has profound implications on clinical management.
• •LVOTO can occur even in the absence of left ventricular hypertrophy, and stress testing or chemical provocation may be necessary to unmask LVOTO.

Despite a battery of testing, a subset of athletes may not receive a unifying diagnosis for their syncope. In athletes with recurrent syncope, the ambiguity about a specific diagnosis often leads to costly repeat testing and withholding the athlete from competitive play. The athlete's frustration from this process may cause him or her to hide symptoms from the athletic trainer and physician.

In this case series, we describe 4 cases of athletes with “unexplained” syncope, with significant left ventricular outflow tract obstruction (LVOTO) found as the clear culprit for their syncope. Our findings emphasize that even in the absence of left ventricular hypertrophy (LVH), LVOTO can occur. We also demonstrate the utility of multimodality imaging with provocative testing in eliciting previously occult LVOTO. Finally, these cases highlight how the detection of LVOTO significantly changes clinical management from undergoing cardiac surgery to guiding decisions regarding implantable cardioverter-defibrillator (ICD) placement.

Case 1

A 28-year-old male professional football player presented for a second opinion after multiple episodes of syncope. He experienced a syncopal episode during practice and had an ambulatory monitor placed. He experienced a subsequent syncopal episode on a hot day, during which he lost consciousness for a sustained amount of time and athletic trainers provided immediate medical attention. No cardiopulmonary resuscitation or defibrillation was required, and he spontaneously regained consciousness. The ambulatory monitor during this episode showed no ventricular arrhythmias and sinus tachycardia before the syncopal event. The patient's family history was notable for a “thickened heart” in his father, and his social history noted stimulant and excessive caffeine use. He saw a local primary care physician, who diagnosed him with vasovagal syncope after tilt-table testing.

The ECG was unremarkable. Resting TTE showed asymmetric septal hypertrophy with maximal wall thickness of 20 mm (Video 1). There was no clear valvular systolic anterior motion (SAM) of the mitral valve or LVOTO at rest, with peak gradient <20 mm Hg (Figure 1). Cardiac MRI confirmed basal septal hypertrophy without clear SAM or flow acceleration in the LVOT (Video 2). There was no significant late gadolinium enhancement (LGE). Given his syncope occurred with exertion and concern for LVOTO, a stress TTE was performed (Video 3). He exercised to 18 metabolic equivalents with clear SAM and flow acceleration in the LVOT, with peak gradient near 120 mm Hg (Figure 2).

Figure 1.

Case 1, Football Player: Resting LVOT Gradient

Continuous-wave Doppler across the aortic valve displaying no significant LVOT gradient (<20 mm Hg). LVOT = left ventricular outflow tract.

Figure 2.

Case 1, Football Player: Stress LVOT Gradient

Continuous-wave Doppler across the aortic valve during stress displaying late-peaking dagger signal and significant LVOTO, with peak gradient near 150 mm Hg. LVOT = left ventricular outflow tract; LVOTO = left ventricular outflow tract obstruction.

Given the absence of high-risk HCM features associated with sudden cardiac death and a clear culprit of syncope, ICD was deferred. The patient could only tolerate low-dose beta-blocker and was started on myosin inhibitor, with dramatic reduction in LVOT gradients. After repeat stress TTE on mavacamten did not show LVOTO, he returned to competitive football without further incidents.

Case 2

A 60-year-old female former marathon runner presented with shortness of breath and multiple syncopal episodes with exertion. She described these symptoms as occurring at the onset of running 3 miles. One year ago, she was able to run 6 miles without difficulty. She had a history of a patent foramen ovale, with no other known cardiac history. She was a former smoker with no family history of cardiac disease. Physical examination and initial ECG were unremarkable.

Her TTE showed maximal wall thickness of 11 mm and elongated anterior mitral valve leaflet without clear SAM (Video 4). On color Doppler, there was no clear flow acceleration in the LVOT, and no significant LVOT gradient was obtained (Figure 3). Wall thickness on cardiac MRI measured 11 mm with elongated anterior mitral valve leaflet but no significant SAM or LVOTO (Video 5). There was no evidence of LGE.

Figure 3.

Case 2, Runner: Resting LVOT Gradient

Continuous-wave Doppler across the aortic valve displaying no significant LVOT gradient (<20 mm Hg). LVOT = left ventricular outflow tract.

Given the limitations of a recent knee injury, isoproterenol-guided transesophageal echocardiography (TEE) was pursued to evaluate for SAM and assess for LVOTO (Video 6). There was clear SAM with turbulent flow acceleration in the LVOT, and LVOT gradient >100 mm Hg was obtained on transgastric views (Figure 4). After extensive shared decision-making with the athlete, she decided to pursue septal myectomy and mitral valve plication, with improvement in symptoms. Repeat provocative testing did not show residual LVOTO. After recovery from knee injury and cardiac surgery, she was able to resume running without reproduction of symptoms or syncope.

Figure 4.

Case 2, Runner: Isoproterenol-Provoked TEE Gradient

Using isoproterenol for provocation, continuous-wave Doppler across the aortic valve demonstrated dynamic LVOTO with peak gradient >100 mm Hg. LVOTO = left ventricular outflow tract obstruction; TEE = transesophageal echocardiography.

Case 3

A 56-year-old male masters athlete presented with worsening exertional dyspnea and syncope during intense Peloton workouts. He described extreme dyspnea during the highest intensity portion of his workout, with syncope witnessed by other members at his gym. There was no known past medical history or significant cardiac family history. Initial ECG (Figure 5) was borderline for LVH, with subsequent TTE showing wall thickness of 11 mm. The TTE had suggestion of SAM with elongated anterior mitral valve leaflet, but a maximal LVOT gradient of only 23 mm Hg was obtained (Figure 6). Cardiac MRI confirmed a wall thickness of 11 mm without evidence of LGE (Figure 7). Given suspicion for SAM and significant LVOTO, the patient underwent stress TTE, which demonstrated significant SAM and LVOTO, with peak gradient of >100 mm Hg (Video 7).

Figure 5.

Case 3, Masters Athlete: Electrocardiogram

Electrocardiogram demonstrating sinus rhythm with borderline left ventricular hypertrophy.

Figure 6.

Case 3, Masters Athlete: Resting LVOT Gradient

Continuous-wave Doppler across the aortic valve displaying no significant LVOT gradient (<20 mm Hg). LVOT = left ventricular outflow tract.

Figure 7.

Case 3, Masters Athlete: Cardiac MRI

Cardiac MRI demonstrating maximal wall thickness of 11 mm. There was no evidence of LGE. LGE = late gadolinium enhancement; MRI = magnetic resonance imaging.

Given the patient's symptoms and syncopal episodes secondary to LVOTO, he was started on metoprolol. His symptoms and LVOTO persisted, so after shared decision-making, he elected to start myosin inhibitor therapy instead of cardiac surgery. The patient's symptoms improved significantly with mavacamten, and he was able to resume his previous elite level of aerobic activity without further events.

Case 4

A 40-year-old male former track athlete presented with palpitations, worsening dyspnea, and presyncopal episodes. He was told that he had HCM as a child and was started on atrioventricular nodal blocking agents, with improvement but not resolution of symptoms. His symptoms had worsened over the past year, specifically with jogging or running. He had a heart monitor, which showed brief runs (<30 seconds) of supraventricular tachycardia. TTE demonstrated wall thickness of 12 mm with flow acceleration in the LVOT. Continuous-wave Doppler across the aortic valve with Valsalva maneuver showed 2 discrete profiles: an early peaking signal consistent with fixed obstruction and a late peaking signal suggestive of dynamic obstruction (Figure 8).

Figure 8.

Case 4, Track Athlete: Resting TTE Gradients

Continuous-wave Doppler across the aortic valve with Valsalva maneuver showed 2 discrete profiles: an early peaking signal consistent with fixed obstruction and a late peaking signal suggestive of dynamic obstruction. TTE = transthoracic echocardiography.

For further investigation, the patient underwent cardiac MRI. Maximal left ventricular wall thickness was 12 mm, and subaortic flow acceleration was noted with the presence of a subaortic membrane (Video 8, Figure 9). TEE confirmed the presence of a subaortic membrane and dynamic obstruction with isoproterenol provocation, evidenced by SAM and flow acceleration in the LVOT (Video 9). Fixed and dynamic LVOT gradients were obtained, with dynamic gradient over 100 mm Hg (Figure 10). The patient underwent cardiac surgery with resection of subaortic membrane and septal myectomy. After surgery and cardiac rehabilitation, he reported improvement in symptoms.

Figure 9.

Case 4, Track Athlete: Cardiac MRI

Three-chamber view demonstrating subaortic flow acceleration and presence of subaortic membrane (arrow). MRI = magnetic resonance imaging.

Figure 10.

Case 4, Track Athlete: TEE Gradients

(A) Continuous-wave Doppler across the aortic valve demonstrating early peaking gradient consistent with fixed obstruction secondary to subaortic membrane. (B) With isoproterenol, dynamic late peaking signal (150 mm Hg) was obtained, consistent with significant LVOTO. LVOTO = left ventricular outflow tract obstruction; TEE = transesophageal echocardiography.

Discussion

In this case series, we present 4 cases of athletes with syncope of previously unknown etiology who were found to have significant LVOTO. The detection of LVOTO had significant clinical implications in each of these cases. Two patients were referred to cardiac surgery and 2 were referred for myosin inhibitor therapy, with dramatic improvement in symptoms. All athletes were able to return to competitive sports at their desired level of participation. In case 1 (HCM in a professional football player), the detection of LVOTO as the culprit of syncope was critical in the risk stratification of sudden cardiac death. In the absence of detecting LVOTO, the athlete may have been labeled as an HCM patient with “unexplained syncope” and received an ICD.⁴

In HCM patients in general, there may be an under-recognition of LVOTO as the culprit for syncope. LVOT gradients are dynamic: Excess heat, poor hydration, and stimulant use may all exacerbate gradients in athletes enough to cause syncope. The inability to recognize significant LVOTO not only comes with the missed opportunity to provide definitive treatment with surgery or myosin inhibitors, but it has other downstream consequences. For example, HCM patients with syncope due to unrecognized LVOTO may have an ambulatory monitor performed that records 8 beats of nonsustained ventricular tachycardia. Although guidelines indicate that this degree of nonsustained ventricular tachycardia does not meet the criteria for ICD, cardiologists may be inclined to place an ICD in the background of unexplained syncope.⁴

It is important for clinicians to recognize that LVOTO may occur even in the absence of overt LVH owing to structural abnormalities of the mitral-subvalvular apparatus. Leaflet elongation, papillary muscle displacement, and accessory chordae can precipitate obstruction despite normal wall thickness.⁵ In fact, recent geometric analyses have shown specific factors such as reduced aortomitral angle, increased anterior leaflet length, and elevated coaptation height may be more responsible for LVOTO than left ventricular wall thickness.⁶ Clinical series have demonstrated dynamic LVOTO in patients with only mildly increased or even normal wall thickness, again highlighting the importance of geometry rather than wall thickness alone.⁷ This has important surgical implications, as mitral valve interventions such as plication are needed to effectively relieve LVOTO.

In symptomatic patients who are anatomically predisposed to LVOTO (eg, elongated anterior mitral valve leaflet), it is critical that some sort of provocative testing is performed. As shown in this case series, severely elevated LVOT gradients can be seen with provocative testing despite no significant gradient obtained at rest. In patients who cannot exercise or who have poor acoustic windows, TEE with isoproterenol has been shown to provide a viable alternative with excellent spatial resolution to detect SAM and capture LVOT gradients.^8,9 One important limitation is that the standard Bruce protocol may not be sufficient for elite athletes to reproduce symptoms that they experienced with training or during competition.¹⁰ Further studies are needed to evaluate the efficacy of tailored protocols for individual athletes or the utility of the cardiopulmonary exercise test with TTE imaging in athletic populations.¹⁰

Visual Summary.

Key Points When Evaluating the LVOT in Athletes With Syncope

The figure highlights the importance of considering the intrinsic anatomy of mitral valve, recognizing limitations of rest imaging and importance of provocation, and how detection of LVOTO can drastically change management. AML = anterior mitral valve leaflet; CW = continuous wave; ICD = implantable cardioverter-defibrillator; LVH = left ventricular hypertrophy; LVOT = left ventricular outflow tract; LVOTG = left ventricular outflow tract gradient; LVOTO = left ventricular outflow tract obstruction; SAM = systolic anterior motion; Iso-TEE = isoproterenol-provoked transesophageal echocardiography; TTE = transthoracic echocardiography.

Funding Support and Author Disclosures

The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Appendix

Video 1

Case 1, Football Player: Resting TTE

Parasternal long-axis view demonstrates basal septal hypertrophy. The patient had an elongated anterior mitral valve leaflet but no clear evidence of SAM or dynamic obstruction.

Video 2

Case 1, Football Player: Cardiac MRI

(A) Short-axis stack SSFP cine images demonstrating basal septal hypertrophy up to 21 mm. (B) Gradient echo parasternal long-axis sequences demonstrating elongated anterior mitral valve leaflet with no clear evidence of SAM or flow acceleration in the LVOT.

Video 3

Case 1, Football Player: Stress TTE

Apical 3-chamber view demonstrates clear SAM and color flow acceleration in the LVOT.

Video 4

Case 2, Runner: Baseline TTE

Parasternal long-axis view demonstrating mildly increased wall thickness (11 mm) with elongated anterior mitral valve leaflet. There was no clear evidence of SAM or flow acceleration in the LVOT.

Video 5

Case 2, Runner: Cardiac MRI

Parasternal long-axis view demonstrating elongated anterior mitral valve leaflet with septum measuring 11 mm. No clear evidence of SAM or flow acceleration in the LVOT is shown.

Video 6

Case 2, Runner: Isoproterenol-Guided TEE

Using isoproterenol for provocation, there was clear demonstration of SAM and flow acceleration in the LVOT.

Video 7

Case 3, Masters Athlete: Stress TTE

Stress TTE demonstrating SAM with significant LVOTO. Peak gradient was >100 mm Hg.

Video 8

Case 4, Track Athlete: Cardiac MRI

Three-chamber view demonstrating maximal wall thickness of 12 mm with subaortic flow acceleration and the presence of a subaortic membrane.

Video 9

Case 4, Track Athlete: Isoproterenol-Guided TEE

Three-chamber TEE view demonstrating the presence of subaortic membrane and SAM with color flow turbulence with isoproterenol provocation.