Coronary tortuosity identifies a distinct ischemic phenotype in patients with functional ischemia and non-obstructive coronary arteries

Background

A substantial proportion of patients referred for invasive coronary angiography after positive functional ischemia testing do not demonstrate obstructive coronary artery disease. Coronary tortuosity has been proposed as a structural contributor to ischemia in non-obstructive coronary syndromes, yet its clinical phenotype remains poorly defined.

Purpose

To evaluate coronary tortuosity as a structural ischemic phenotype among patients with positive functional ischemia testing and no obstructive coronary artery disease.

Methods

In this single-center, two-year study, 936 consecutive patients undergoing invasive coronary angiography after positive functional testing were included. All non-invasive tests were positive, reflecting referral-based selection. Modalities included SPECT (426/936), stress echocardiography (308/936), and exercise ECG (202/936).

Mean age was 65.8 years; 70.8% were male; mean LVEF was 56%. Hypertension was present in 79.6%, dyslipidemia in 84.3%, diabetes in 41.8%, smoking in 43.2%, and overweight/obesity in 49.5%. Angina was reported by 41.2%.

Anatomical concordance was defined as ≥60% stenosis in the vessel supplying the ischemic territory (or any major vessel for exercise ECG). Coronary tortuosity (>4 consecutive curvatures) was quantified in the left anterior descending artery for standardization. The tortuosity index (TI) was calculated as the ratio of actual vessel length to straight-line distance between proximal and distal reference points; values >1.3–1.4 were considered abnormal. Odds ratios (OR) were calculated.

Results

Of 936 patients, 422 (45.1%) were non-concordant. Tortuosity was present in 134/422 (31.8%) versus 12/514 concordant cases (2.3%) (OR≈19, p<0.001).

Although women comprised less than one-third of the cohort, they were significantly overrepresented in the tortuosity subgroup (OR≈3.2, p<0.001), becoming the predominant sex within this phenotype.

Within non-concordant patients, tortuosity was associated with higher BMI (OR≈1.7, p<0.01) and angina (OR≈1.8, p<0.01). Hypertension was highly prevalent overall and did not reach statistical significance, likely due to limited variability, but frequently coexisted. Revascularization was rare.

Conclusion

Among patients with positive functional ischemia testing and no obstructive coronary artery disease, coronary tortuosity identifies a structural ischemic phenotype characterized by female predominance, elevated BMI, angina, and frequent arterial hypertension. Despite the male predominance of the overall cohort, women were disproportionately represented within this subgroup. These findings suggest a symptomatic subpopulation within non-obstructive coronary syndromes in whom angiographically visible tortuosity may represent a structural marker of underlying microvascular dysfunction. Prospective physiological validation is warranted.