METHODS

RESULTS

In total, 307 patients were identified, but 36 were excluded from analysis; 22 did not have LBBB upon ECG review, 1 reported chest pains, and 14 did not have sufficient follow-up data. Of the remaining 271 eligible patients, Table I outlines their baseline characteristics. The mean age was 40.2 ± 7.4 yr; 97% were male, 99% were Caucasian, 189 (70%) had a Flying Class II (pilots/navigators) waiver, and 39 (15%) had a Flying Class III (aircrew) waiver. The mean weight was 177 ± 24.3 lbs, with a body mass index of 25.2 ± 2.8 kg · m⁻². There were 63 patients (23%) with hyperlipidemia, 55 (20%) with hypertension, 44 (16%) with CV family history, 88 (33%) with a smoking history, and 44 (16%) who had experienced childhood infection. A total of 37 patients met the definition for CAD and 13 for CM. In addition, 244 patients (85%) had normal ECG axis, 35 (12%) had left axis deviation, and 5 (1.8%) had right axis deviation.

Table I. Baseline Patient Characteristics at Time of Diagnosis.

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A total of 203 patients (203 out of 271, 75%) had noninvasive stress tests performed; 122 had initial treadmill alone, 69 had myocardial perfusion scan, and 11 had treadmill stress echocardiography. Most treadmill tests were reported as clinically normal (86 out of 122, 70.5%) indicating patients had high functional capacity without symptoms, while a portion of the tests (25 out of 122, 20.5%) were deemed uninterpretable. Myocardial perfusion scans predominantly showed abnormal results, with septal defects observed in the majority (51 out of 69, 74%), in contrast to stress echocardiograms, where the majority (9 out of 11, 81%) were reported normal.

A total of 147 patients (54%) underwent invasive coronary angiography, and 18 (6.6%) had coronary computed tomography angiography (CCTA), 7 of whom also had invasive coronary angiography. Of the 158 patients who had direct coronary evaluation either by invasive coronary angiography or CCTA, we found 6 patients who had only coronary calcification. Luminal irregularities, defined as <20% aggregate stenosis, were found in 10 patients. Mild CAD was defined as aggregate stenosis of 20–49% and was found in 9 patients. Moderate CAD (aggregate ≥50–119% stenosis) was demonstrated in 7 patients, and severe CAD (aggregate stenosis over 120%) was seen in 5 patients (Fig. 1). Two patients had percutaneous coronary intervention: one with moderate and the other with severe aggregate CAD. At diagnosis, hyperlipidemia, hypertension, and family history were significant risk factors for CAD, but flying class, smoking, and a history of childhood infection were not (Table II). These findings persisted over time during follow-up.

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Table II. Comparison of Clinical Variables for those with Coronary Artery Disease and Cardiomyopathy at Time of Diagnosis and on Follow-Up.

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LVEF assessment was obtained in 139 patients (139 out of 271, 51%); using 125 transthoracic echocardiograms, 10 had an invasive left ventriculogram, and 4 with multigated acquisition scan. Among patients with CM, the mean LVEF was 40.8 ± 7.5%. Of these, 12 patients had nonischemic CM and 1 had ischemic CM. Preselected clinical variables were not statistically significant for CM at the time of diagnosis or on follow-up (Table II).

A total of 177 patients (177 out of 271, 65%) with a mean follow-up of 24.5 ± 16.1 yr revealed an additional 30 patients with CAD, but only 16 had corresponding coronary angiography on file. Of these 30, there were 2 with only coronary calcifications, 2 with luminal irregularities, 1 with mild CAD, 2 with severe CAD, 5 with myocardial infarction (MI), 2 with percutaneous coronary intervention, and 1 with coronary artery bypass grafting; none of these were overlapping entities (Fig. 2).

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CM was identified in 37 patients: 7 nonischemic causes (1 had hypertrophic CM), 6 ischemic CM, and 24 with unclear etiology. Two patients had cardiac MRI documented: one exhibited a reduced LVEF with subepicardial and midepicardial late gadolinium enhancement, while the other underwent the procedure due to a dilated aorta with preserved LVEF and showed no gadolinium enhancement. Six patients later underwent placement of an implantable cardioverter-defibrillator. The percentage of individuals receiving cardiac resynchronization therapy was not specified.

There were 41 confirmed deaths with a mean age of 75.1 ± 14.1 yr. Of the nine premature deaths, one died from MI, one from ventricular fibrillation, one from sudden cardiac arrest, one from cardiac arrest during diagnostic catheterization, one from lung cancer, one from upper gastrointestinal bleed, and two from unknown causes.

DISCUSSION

The ECG Library was established at USAFSAM in 1957 with the aim to collect and store ECGs on all USAF rated flying personnel and all its applicants for flying or navigator training. The ECG Library now contains well over 1.2 million tracings and allows Aeromedical Consultation Service at USAFSAM to conduct thorough review of ECGs on any flying personnel. In most instances, these aircrew members were asymptomatic, and ECGs were obtained during routine screenings.

LBBB is the result of delayed conduction down the left bundle branch, within its fascicles, Purkinje fibers, or any combination of these. As such, the right ventricular activation occurs first followed by left ventricular endocardium, then midseptal wall, with remainder of the LV activating in a delayed fashion ending in the lateral, basal region.¹⁹ This electrical and mechanical dyssynchrony has been linked to different regional ventricular workloads potentially leading to left ventricular dilation and remodeling.⁴ According to longitudinal community-based studies from The Framingham Heart Study, presence of LBBB is associated with increased risk for CAD or heart failure and overall CV mortality, especially in older men (mean age at onset of LBBB was 62 yr).^16,17 Framingham also demonstrated QRS duration to positively correlate with left ventricular mass and dimensions but inversely associate with fractional shortening.⁷ Retrospective data from the National Health and Nutrition Examination Survey cohort, with a mean age of 60.5 ± 13.6 yr, found QRS duration in setting of LBBB as an independent predictor of CV mortality (hazard ratio = 2.4, confidence interval = 1.3-4.7, P = 0.009).² Other unselected patient data demonstrated similar findings. Participants from the SPPARCS study, a community-based cohort study of those >55 yr old in Sonoma County, CA, overall had 2.5% prevalence of LBBB at baseline. During 6 yr of follow-up, heart failure incidence and CV mortality were higher in those with LBBB than those without LBBB.¹ Additionally, those with underlying CV disorders and LBBB have worse overall outcomes when compared to those with CVD alone.³

Contrary to the aforementioned studies, population-based data from Atherosclerosis Risk in Communities (ARIC)¹² and Belgian Inter-University Research on Nutrition and Health (BIRNH)⁶ did not demonstrate death from coronary heart disease in those with LBBB. Earlier publications on asymptomatic, young Air Force aviators with LBBB have likewise shown no significant increase in CV disease or mortality.^11,13,15

Our paper represents the most updated aeromedical data since Rotman et al. published their findings in 1975 on USAF flying personnel. Overall, our population was young (average age at diagnosis was 40 yr) and generally healthy, with a minority having smoking, hypertension, hyperlipidemia, and family history as risk factors for CV disease. More than 70% of patients had initial stress testing done, with the majority of these being treadmill alone. We meticulously reviewed all available exercise treadmill test tracings, noting instances of resolved ST-T wave abnormalities at peak exercise, while acknowledging that some remained nondiagnostic. Notably, the designation of “normal” pertains specifically to tests conducted on patients exhibiting exceptionally high functional capacity. In contrast, a large proportion of myocardial perfusion scans were interpreted as abnormal. This is consistent with prior studies demonstrating reduced specificity with myocardial perfusion scans in detecting CAD in those with LBBB given higher false positive septal perfusion defects.²⁰ Similarly, stress echocardiography may reveal septal wall motion abnormalities affecting overall specificity, but our cohort had mostly (81%) normal results. Admittedly, multislice computed tomography has excellent negative predictive value in excluding CAD,¹⁴ but this technology was not available to our earlier cohort. The noninvasive tests were selected based on the available options at the time of diagnosis. Likewise, while cardiac MRI was not widely accessible for most of our cohort, its availability would have undoubtedly enhanced our diagnostic accuracy.

The initial coronary angiography revealed a total of 12 patients with moderate or severe aggregate CAD, but only 2 required revascularization at time of diagnosis, suggesting most CAD diagnoses at baseline were nonobstructive. Nevertheless, during the follow-up period, there were 5 newly identified cases of MI, an additional 2 instances of stent placements, and 1 coronary artery bypass grafting procedure. Additionally, there were 9 premature deaths, with 5 attributed to cardiac causes. CM was found in 20% of aircrew at some point in the study. These individuals underwent follow-up assessments typically spanning from 1–3 yr. Importantly, no instances of loss of life or aircraft occurred while individuals were on flight status within the study. All identified diseases were addressed, treated, and monitored in accordance with the prevailing USAF policy. Patients with CAD also had higher baseline prevalence for hypertension, hyperlipidemia, and family history than patients with LBBB alone. It is possible that these CV risk factors account for CAD rather than LBBB as a marker. When compared to the previously published data from Aeromedical Consultation Service, our data demonstrated higher rates of baseline CM (LVEF < 50%).¹⁸ This discrepancy may be explained by a couple of factors. Firstly, there were only 49% of patients who had any LVEF evaluation performed. Secondly, several different imaging modalities were used limiting overall precision and quality over time. Interestingly, none of the preselected clinical variables were found to impact the development of CM. Aircrew regularly exposed to higher G-forces were also not at higher risk for CAD or CM. Death from sudden cardiac arrest was rare. These findings suggest LBBB may be a preclinical manifestation of underlying myocardial abnormality or perhaps a trigger to developing CM.

A significant limitation is the incompleteness of data, as follow-up was only available in two-thirds of our initial cohort. Given the 63-yr time span of this study, certain imaging modalities were not accessible to earlier cohorts, while guideline recommendations for LBBB workup have also evolved over time. These changes in recordkeeping practices, technology, or diagnostic criteria may potentially affect the consistency and comparability of data over different time periods. Incomplete or missing data, selection bias (inclusion of patients based on availability of medical records), and information bias (accuracy, misinterpretations, or variations of data documentation) may collectively limit the scope, reliability, and generalizability of our findings. For example, we had to exclude Holter data from analysis as we only had data for 51 patients, with none resulting in any significant arrhythmias. Additionally, establishing causation between variables is challenging in retrospective chart reviews; associations identified may not imply causation.

In this retrospective analysis, identification of LBBB in young, asymptomatic, and healthy Caucasian male aviators in the USAF correlated to an elevated risk of CM and a trend toward increased CAD, both at the time of diagnosis and longitudinally, but a low occurrence of sudden death. Current USAF policy of echocardiogram, noninvasive stress testing, and angiography (either invasive or CT coronary angiography) is warranted. Cardiac MRI should also strongly be considered. Follow-up testing every 1–3 yr should be done in all aircrew with LBBB. Further research is advised to validate and elaborate on these findings.