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Background and Objectives: There is an increasing interest in the coronary tortuosity as a novel pathophysiological mechanism of ischemia in coronary artery disease without significant obstruction, but there are a lack of studies to confirm this relationship in the clinical setting. The aim of our study was to evaluate the association of severe coronary tortuosity and the potential role of coronary blood supply dominance in the appearance of myocardial ischemia in patients with non-obstructive coronary artery disease (non-CAD), compared to patients with obstructive coronary artery disease (CAD). Materials and Methods: The study enrolled 131 participants (71 male and 60 female), recruited among patients referred to cardiologists due to angina symptoms with ischemic alterations established by cardiac stress tests, as well as those admitted to the hospital for acute coronary syndrome. Results: Mean age of recruited patients was 61.6 (±10.1) years. According to the coronary angiography, they were divided into two groups: non-obstructive and obstructive CAD (77 and 54, respectively). There were significantly more women (61% vs. 24%, p < 0.001) in the non-CAD group. Both tortuous coronary arteries (50.6% vs. 14.8%, p < 0.001) and left coronary dominance (37.7% vs. 16.7%, p = 0.006) were more frequent in the non-CAD group compared to the CAD group. Female sex (OR = 17.516, p = 0.001), tortuous coronary arteries (OR = 7.962, p = 0.006) and left dominance of blood supply were significant predictors for non-CAD. Conclusions: Non-obstructive CAD is common among patients, especially women, who are referred for coronary angiography. Severe coronary artery tortuosity is the strongest independent predictor of non-obstructive CAD, followed by female gender and left coronary dominance.

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AIMS: Spontaneous coronary artery dissection (SCAD) is an increasingly diagnosed cause of myocardial infarction with unclear pathophysiology. The aim of the study was to test if vascular segments site of SCAD present distinctive local anatomy and hemodynamic profiles. METHODS: Coronary arteries with spontaneously healed SCAD (confirmed by follow-up angiography) underwent three-dimensional reconstruction, morphometric analysis with definition of vessel local curvature and torsion, and computational fluid dynamics (CFD) simulations with derivation of time-averaged wall shear stress (TAWSS) and topological shear variation index (TSVI). The (reconstructed) healed proximal SCAD segment was visually inspected for co-localization with curvature, torsion, and CFD-derived quantities hot spots. RESULTS: Thirteen vessels with healed SCAD underwent the morpho-functional analysis. Median time between baseline and follow-up coronary angiograms was 57 (interquartile range [IQR] 45-95) days. In seven cases (53.8%), SCAD was classified as type 2b and occurred in the left anterior descending artery or near a bifurcation. In all cases (100%), at least one hot spot co-localized within the healed proximal SCAD segment, in 9 cases (69.2%) ≥ 3 hot spots were identified. Healed SCAD in proximity of a coronary bifurcation presented lower TAWSS peak values (6.65 [IQR 6.20-13.20] vs. 3.81 [2.53-5.17] Pa, p = 0.008) and hosted less frequently TSVI hot spots (100% vs. 57.1%, p = 0.034). CONCLUSION: Vascular segments of healed SCAD were characterized by high curvature/torsion and WSS profiles reflecting increased local flow disturbances. Hence, a pathophysiological role of the interaction between vessel anatomy and shear forces in SCAD is hypothesized.

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Coronary tortuosity has been recognized as a potential pathophysiological mechanism in the development of non-obstructive coronary artery disease (CAD). The aim of this study was to examine the role of two coronary tortuosity measurement methods in the detection of clinically significant coronary tortuosity. The study included 160 patients with angina symptoms and myocardial ischemia detected by cardiac stress tests in chronic settings and those diagnosed with acute coronary syndrome. After coronary angiography, tortuosity of coronary arteries was assessed by two methods, including measurement of tortuosity angles and calculating of tortuosity index. Significantly more tortuous coronary arteries were detected in the group with non-obstructive CAD (p < 0.01 for all three arteries), with significantly higher tortuosity index (TI) for all three coronary arteries in this group of patients, compared to patients with obstructive CAD. The highest TI for LCX was found in patients with lateral ischemia (p < 0.001) and for LAD in patients with anterior ischemia (p < 0.001). When measured by the angle method, the only association was found between LCX tortuosity and lateral ischemia (OR 4.9, p = 0.046). In conclusion, coronary tortuosity represents a pathophysiological mechanism for myocardial ischemia in non-obstructive CAD. The coronary tortuosity index could be a reliable and widely applicable tool for the quantification of coronary tortuosity.

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The aim of this paper was to review based on the existing literature the impact of coronary artery tortuosity on coronary pathology. Primarily, an attempt was made to establish the implication of coronary tortuosity as a physio-pathological mechanism of inducing ischemia in patients with non-obstructive coronary artery disease (CAD). Because the prevalence of tortuosity is higher in severe hypertensive patients, a second purpose of this paper was to review this association by understanding the physio-pathological processes and fluid dynamics in hypertrophic heart. Particularly, the effect of coronary tortuosity on systolic function with reference to longitudinal function and ventricular relaxation was addressed. Finally, the technical difficulties imposed by coronary tortuosity to percutaneous coronary interventions were discussed.

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OBJECTIVES: The authors sought to determine whether coronary artery tortuosity negatively affects clinical outcomes after stent implantation. BACKGROUND: Coronary artery tortuosity is a common angiographic finding and has been associated with increased rates of early and late major adverse events after balloon angioplasty. METHODS: Individual patient data from 6 prospective, randomized stent trials were pooled. Outcomes at 30 days and 5 years following percutaneous coronary intervention of a single coronary lesion were analyzed according to the presence or absence of moderate/severe vessel tortuosity, as determined by an angiographic core laboratory. The primary endpoint was target vessel failure (TVF) (composite of cardiac death, target vessel-related myocardial infarction [TV-MI], or ischemia-driven target vessel revascularization [ID-TVR]). RESULTS: A total of 6,951 patients were included, 729 of whom (10.5%) underwent percutaneous coronary intervention in vessels with moderate/severe tortuosity. At 30 days, TVF was more frequent in patients with versus without moderate/severe tortuosity (3.8% vs. 2.4%; hazard ratio [HR]: 1.64; 95% confidence interval [CI]: 1.09 to 2.46; p = 0.02), a difference driven by a higher rate of TV-MI. At 5 years, TVF remained increased in patients with moderate/severe tortuosity (p = 0.003), driven by higher rates of TV-MI (p = 0.003) and ID-TVR (p = 0.01). Definite stent thrombosis was also greater in patients with versus without moderate/severe tortuosity (1.9% vs. 1.0%; HR: 1.86; 95% CI: 1.02 to 3.39; p = 0.04). After adjustment for baseline covariates, moderate/severe vessel tortuosity was independently associated with TV-MI and ID-TVR at 5 years (p = 0.04 for both). CONCLUSIONS: Stent implantation in vessels with moderate/severe coronary artery tortuosity is associated with increased rates of TVF due to greater rates of TV-MI and ID-TVR.

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Background: A large proportion of patients with angina and no obstructive coronary artery disease (ANOCA) has underlying coronary vasomotor dysfunction (CVDys), which can be diagnosed by a coronary function test (CFT). Coronary tortuosity is a common angiographic finding during the CFT. Yet, no data exist on the association between vasomotor dysfunction and coronary tortuosity. Aim: To investigate the association between CVDys and coronary tortuosity in patients with ANOCA Methods: All consecutive ANOCA patients who underwent clinically indicated CFT between February 2019 and November 2020 were included. CFT included acetylcholine spasm testing to diagnose epicardial or microvascular spasm, and adenosine testing to diagnose microvascular dysfunction (MVD). MVD was defined as an index of microvascular resistance (IMR) ≥ 25 and/or coronary flow reserve (CFR) <2.0. Coronary tortuosity, was scored (no, mild, moderate or severe) based on the angles of the curvatures in the left anterior descending (LAD) artery on angiography. Results: In total, 228 patients were included (86% female, mean age 56 ± 9 years). We found coronary artery spasm in 81% of patients and MVD in 45% of patients (15%: abnormal CFR, 30%: abnormal IMR). There were 73 patients with no tortuosity, 114 with mild tortuosity, 41 with moderate tortuosity, and no patients with severe tortuosity. No differences were found in cardiovascular risk factors or medical history, and the prevalence of CVDys did not differ between the no tortuosity, mild tortuosity and moderate tortuosity group (82, 82, and 85%, respectively). Conclusion: In this study, CVDys was not associated with coronary tortuosity. Future experimental and clinical studies on the complex interplay between coronary tortuosity, wall shear stress, endothelial dysfunction and coronary flow are warranted.

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BACKGROUND: Coronary tortuosity (CT) is commonly encountered in postmenopausal females and is usually present without obstructive lesions. Circulating sclerostin levels are elevated in postmenopausal females. In view of sclerostin's vasculoprotective effect, we aimed to find possible association between circulating sclerostin and CT. METHOD: We prospectively enrolled 273 consecutive postmenopausal females with non-obstructive coronary artery disease diagnosed by coronary angiography. Presence and severity (by tortuosity score) of CT as well as serum sclerostin levels were assessed for each patient. RESULTS: Patients with CT (128, 47% of study group) were significantly older (P < 0.001), with higher prevalence of hypertension (P = 0.001) and had significantly higher levels of both sclerostin (P < 0.001) and hs-CRP (P = 0.001). Multivariate binary logistic regression revealed that the presence of CT (dependent variable) was associated with high sclerostin level (OR 8.9, 95% CI: 4.9-16.2, P < 0.001). Using ROC curve analysis, Sclerostin at a cut-off value of >650 pg/ml was found to be associated with presence of CT (AUC 0.69, 95% CI: 0.61-0.75, P < 0.001) with sensitivity and specificity of 75% and 72.4%, respectively. Using Pearson's correlation analysis, significant positive correlation between sclerostin and severity of CT was found (r = 0.29, P = 0.001). CONCLUSION: High circulating sclerostin is associated with the presence and severity of CT in postmenopausal females. This may add to the literature on the incompletely understood pathogenesis of CT.

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OBJECTIVE: Coronary tortuosity may affect epicardial coronary arterial blood flow. This study aimed to investigate the effect of coronary tortuosity on coronary flow reserve and the coronary microcirculation in patients without apparent coronary atherosclerosis. METHODS: Prospective patients (n = 8, 3 men, mean age: 58 ± 6.0 years) with coronary tortuosity and without apparent coronary atherosclerosis were enrolled. Coronary tortuosity was defined by the finding of ≥three bends (defined as a ≥45° change in vessel direction) along the main trunk of the left anterior descending artery or left circumflex artery. Coronary flow reserve and the index of microcirculatory resistance were measured by the thermodilution technique. RESULTS: A total of eight coronary arteries with coronary tortuosity were analyzed. The mean fractional flow reserve was 0.98 ± 0.007. The mean coronary flow reserve was 1.5 ± 0.3, which is much lower than that in the normal coronary artery as reported in the literature. The mean index of microcirculatory resistance was 26.7 ± 2.3, which is much higher than that in the normal coronary artery. CONCLUSIONS: Coronary tortuosity is associated with decreased coronary flow reserve and an increased index of microcirculatory resistance.Trial registration: This study is registered at the Chinese Clinical Trial Registry, NCT No: ChiCTR2000033671.

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The relationship between coronary tortuosity (CorT) and tissue-level myocardial perfusion is not clear. We investigated tissue perfusion in myocardial territories supplied by tortuous coronary arteries. Among patients who had undergone coronary angiography, patients with reported CorT, those with ≥1 coronary artery were included in the study group (100 patients). The control group included patients with normal coronary arteries (100 patients). Thrombolysis In Myocardial Infarction frame count (TFC) and myocardial blush grade (MBG) were calculated for each coronary artery. Mean TFC was significantly higher in tortuous right coronary artery (RCA), left anterior descending (LAD) artery, and circumflex (Cx) artery compared to their non-tortuous counterparts (28.81 ± 6.463 vs 21.94 ± 3.328, P = .009; 43.28 ± 5.698 vs 36.17 ± 3.875, P = .006; 29.35 ± 4.111 vs 23.821 ± 2.639; P < .001, respectively). Mean MBG was also significantly lower in tortuous RCA, LAD, and Cx, compared to their normal counterparts (2.78 ± 0.417 vs 2.98 ± 0.155, P < .001; 2.74 ± 0.483 vs 2.97 ± 0.164, P < .001; 2.92 ± 0.277 vs 2.99 ± 0.110, P < .001, respectively). For each tortuous coronary artery, TFC was similar for every MBG category. Tortuous coronary arteries have higher TFC and lower MBG, suggesting impaired epicardial and microvascular coronary flow, when compared to normal coronary arteries.

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A 66-year-old man with refractory angina was admitted for percutaneous coronary intervention (PCI) through a tortuous saphenous vein graft sequentially anastomosed with a diagonal and a first marginal branch. Our target was a critical stenosis at the retrograde limb of the first marginal proximal to saphenous vein graft anastomosis. Stent delivery to our target lesion mandated tracking through sequential angulations. In this case, we enhanced the support of the guide catheter and delivered a stent on the retrograde limb of the first marginal branch with very deep intubation of the guide catheter into the saphenous vein graft and use of a buddy wire, which is a cheaper and relatively safer maneuver than complex techniques such as the double guide-catheter extension technique. Proper selection of the type and size of the guide catheter and meticulous attention to the pressure waveform in order to avoid ischemia or dissection of the graft is mandatory during this technique.

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INTRODUCTION: Coronary tortuosity (CorT) is a common coronary angiographic finding. The aetiology, clinical implication and long-term prognosis are not well clarified. Mitral annular calcification (MAC) is one of the most common cardiac structural abnormalities on echocardiographic examination. MAC and CorT are associated with atherosclerotic risk factors such as advanced age, hypertension, diabetes mellitus, hypercholesterolaemia, female gender and chronic kidney disease. There are few data on the co-existence of MAC and CorT in the literature. This study was conducted with the aim of evaluating the association between CorT and MAC. METHODS: The medical records of consecutive patients who underwent coronary angiography were retrospectively reviewed. The study group consisted of 2 736 patients. Taking into consideration the inclusion criteria, 392 patients with MAC and 687 patients without MAC (control group) were included in the study. Biochemical, clinical and echocardiographic parameters and CorT were evaluated in all patients. CorT was defined as three fixed bends during both systole and diastole, with the angle of each bend 45° or more. RESULTS: Patients with MAC had a higher prevalence of hypertension, hyperlipidaemia, female gender, MAC and advanced age. On univariate analysis, advanced age, hypertension, female gender, hyperlipidaemia and MAC were associated with CorT. On multivariate analysis MAC, advanced age and hypertension were independent predictors for CorT (OR 2.167, 95% CI: 1.436-4.283, p < 0.001; OR 1.243, 95% CI: 1.243-3.674, p < 0.001; OR 2.358, 95% CI: 1.864-4.681, p < 0.001, respectively). CONCLUSIONS: In our study, we found a significant relationship between MAC and CorT.

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BACKGROUND: Coronary tortuosity (CT) had different definitions and scores in literature with unclear pathophysiological impact. OBJECTIVES: To study degree of CT and it's relation to ischemic changes in patients with angina but normal coronary angiography (CA). METHODS: We conducted a prospective study at University hospitals between May 2016 and January 2017. We included 200 consecutive patients who underwent CA due to chest pain assumed to be of cardiac origin, and their CA was normal (no diameter stenosis >30%, nor myocardial bridging). Patients were prospectively divided into 2 groups based on the presence (n = 113) or absence (n = 87) of ischemic changes during stress study and compared for clinical, echocardiographic and CA characteristics. A newly proposed Tortuosity Severity Index (TSI) was developed into significant (mild/moderate CT with more than 4 curvatures in total, or severe/extreme CT with any number of curvatures) or not significant TSI (mild CT with curvatures less than or equal to 4 curvatures in total). RESULTS: Patients with ischemic changes had the highest rate of CT (76.5 vs 18%, p = 0.004) compared to those without. CT mostly affects the left anterior descending (LAD) coronary artery in mid and distal segments. Females, elderly, and hypertensives with left ventricular hypertrophy were strongly related to CT. Multivariate logistic regression analysis identified CT with significant TSI as the only predictor of ischemic changes in these patients (OR = 6.2, CI = 2.5-15.3, P = <0.001). CONCLUSIONS: Coronary tortuosity is a strong predictor of anginal pain among patients with normal CA, despite positive stress study. This finding is more pronounced among elderly, hypertensive female patients.

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OBJECTIVE: The impact of coronary tortuosity on coronary atherosclerosis remains unclear. This study was performed to determine to the relationship between coronary tortuosity and the presence of coronary atherosclerosis. METHODS: Tortuosity and the presence of coronary atherosclerosis in the main coronary arteries were evaluated. The coronary artery was divided into non-tortuous and tortuous segments. The incidence of coronary atherosclerosis between the two segments was compared. RESULTS: The prevalence of coronary atherosclerotic stenosis was significantly lower in the tortuous than non-tortuous segment. CONCLUSION: The prevalence of coronary atherosclerotic stenosis is lower in the coronary tortuous than non-tortuous segment, indicating that coronary tortuosity might be considered a protective factor for atherosclerosis.

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Objective The clinical implication of coronary tortuosity is unclear. The present study was conducted to determine the relationships between coronary tortuosity and the high-sensitivity C-reactive protein (hs-CRP) concentration and between coronary tortuosity and cerebrovascular accident in hypertensive patients without coronary artery disease. Methods In total, 236 patients with normal coronary angiography findings were categorized into 3 different groups: control participants (n = 58), who had neither hypertension nor coronary tortuosity; patients with hypertension but no coronary tortuosity (H-NCT group, n = 93); and patients with both hypertension and coronary tortuosity (H-CT group, n = 85). The hs-CRP concentration was measured in every patient, and 168 hypertensive patients were followed up for at least 2 years to check for the development of cerebrovascular accident. Results The hs-CRP concentration was significantly higher in the H-CT group than in the control and H-NCT groups (4.33 ± 3.15 vs. 1.52 ± 1.31 and 2.31 ± 2.09 mg/L, respectively). The incidence of lacunar infarction was higher in the H-CT than H-NCT group during the follow-up. Conclusions Hypertensive patients with coronary tortuosity have a higher serum hs-CRP level concentration and have a higher incidence of lacunar infarction than hypertensive patients without coronary tortuosity.

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Objective To investigate the hemodynamic changes in a tortuous coronary to elucidate the effects of tortuosity on coronary perfusion and wall shear stress (WSS). Methods A single tortuous and non-tortuous patient-specific left anterior descending (LAD) coronary artery cases were selected. Two LAD models with and without coronary tortuosity were reconstructed in Mimics software and then transferred to the ANSYS Fluent software for performing computational fluid dynamics (CFD) simulation. The hemodynamic characteristics of both the LAD models were compared. Results The vessel WSS of the tortuous coronary artery clearly decreased in the bend section where the maximum curvature was larger than 1 mm-1.Such a scenario could led to an inadequate blood supply in the downstream vessels. A low WSS (0-26 Pa) acted on the outer wall of the bend, whereas the inner wall of the bend had a high WSS (>100 Pa). The mean WSS of the non-tortuous and tortuous models was 10.79 Pa and 36.12 Pa, respectively. The overall WSS of the tortuous model was larger compared with that of the non-tortuous model. Conclusions Coronary tortuosity increased the overall WSS, which could delay the progress of coronary atherosclerosis.

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BACKGROUND: The mechanistic basis for tortuosity of the coronary arteries (TCA) is unclear. The aim of this study was to test the hypothesis that the relative degree of systolic longitudinal shortening of the left ventricle that deforms coaxially oriented coronary arteries is associated with TCA. METHODS: Adult subjects undergoing coronary angiography and comprehensive echocardiography within 3 months were classified dichotomously as with (n = 32) or without (n = 42) TCA defined on the basis of number and severity of coronary angles. Systolic left ventricular (LV) longitudinal deformation was determined by mitral annular plane systolic excursion (MAPSE) from both B-mode displacement and tissue Doppler time-velocity integral; data were indexed to LV diastolic long-axis length. RESULTS: There were no differences between groups with respect to age, gender, hypertension, or coronary artery disease. Patients with TCA had significantly (P < .01) lower LV mass index and a shorter total LV diastolic long-axis length (mean, 8.3 ± 1.9 vs 9.1 ± 2.2 cm; P < .01). Despite having a shorter length, those with TCA had greater MAPSE by both methods. MAPSE normalized to diastolic length was significantly greater (P < .01) in those with TCA, which remained the case after excluding subjects with reduced LV ejection fraction. Multiple linear regression found that lateral annular MAPSE had the largest effect size, with a 13-fold increase in likelihood for TCA for every 0.1 of normalized MAPSE. CONCLUSIONS: TCA is not associated with increased LV mass but rather with smaller hearts that have greater relative longitudinal shortening of the left ventricle. This finding suggests that TCA could represent an adaptive response to longitudinal systolic distortion of coaxially oriented coronary arteries that dynamically produce shear stresses associated with expansive coronary remodeling.

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BACKGROUND: Fibromuscular dysplasia (FMD) is a systemic, nonatherosclerotic, noninflammatory vasculopathy that is often overlooked by clinicians. Clinical clues could help in selecting patients for further evaluation for the presence of FMD. Recently, it was observed that tortuosity of the coronary arteries is often present in patients with FMD-related abnormalities of the coronary artery. Therefore, we wondered if the presence of coronary tortuosity might provide a clinical clue to the diagnosis of extracoronary FMD. CASES: We describe 5 cases of FMD in whom diagnostic studies for FMD were initiated because of the presence of coronary tortuosity. FMD was found in all 5 patients in the renal and/or cervical arteries. CONCLUSIONS: Our 5 cases suggest that exertional chest pain in the presence of coronary tortuosity may be helpful in selecting patients for further evaluation for the presence of FMD. Further research should focus on the prevalence of FMD among patients with coronary tortuosity and whether the presence of additional clinical clues (such as the presence of hypertension at young age or pulsatile tinnitus) next to coronary tortuosity can predict the risk for FMD in individual patients.

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BACKGROUND: Increasing evidence suggests a relationship between vitamin D (VD) insufficiency and cardiovascular disease. AIM: We aimed to investigate the association between serum 25-hydroxyvitamin D (25-OH VD) with coronary tortuosity (CT) in patients with normal or near-normal (< 40% stenosis) coronary arteries. METHODS: The present study was cross-sectional and observational. We enrolled 356 consecutive patients who had undergone coronary angiography for suspected ischaemic heart disease and were found to have normal or near-normal coronary arteries. Patients were categorised as VD insufficient (< 30 ng/mL) or VD sufficient (≥ 30 ng/dL). CT was defined as the presence of ≥ three bends (defined as ≥ 45° change in vessel direction) along the main trunk of at least one coronary artery, present both in systole and in diastole. RESULTS: The study populations were divided into two groups according to the presence of CT: patients with CT (n = 103, 29%) and patients without CT (NCT; n = 253, 71%). CT is more frequently seen in elderly women and is positively correlated with hypertension. The incidence of VD insufficiency was significantly higher in the CT group (n = 46, 45%) than in the NCT group (n = 90, 36%; p = 0.005). In further multivariate logistic regression analyses, adjustment for major clinical parameters affecting CT showed statistically significant correlations between 25-OH VD and CT (odds ratio = 0.77, 95% confidence interval 0.66-0.98, p = 0.006). CONCLUSIONS: Vitamin D insufficiency was independently associated with coronary tortuosity.

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