Extrinsic compression of left main coronary artery by aneurysmal pulmonary artery in severe pulmonary hypertension: its correlates, clinical impact, and management strategies

Extrinsic compression of left main coronary artery by aneurysmal pulmonary artery in severe... Abstract Aims Although left main coronary artery (LMCA) compression (Co) by pulmonary artery (PA) aneurysm (A) has been reported in some pulmonary hypertension (PH) series, clinical importance and management of this complication remain to be determined. In this single-centre prospective study, we evaluated correlates, clinical impact, and management strategies of LMCA-Co in patients with PH. Methods and results Our study group comprised 269 (female 166, age 52.9 ± 17.3 years) out of 498 patients with confirmed PH who underwent coronary angiography (CA) because of the PAA on echocardiography, angina or incidentally detected LMCA-Co during diagnostic evaluation with multidetector computed tomography. The LMCA-Co ≥ 50% was documented in 22 patients (8.2%) who underwent CA, and stenosis were between 70% and 90% in 14 of these. Univariate comparisons revealed that a younger age, a D-shaped septum, a higher PA systolic, diastolic, and mean pressures and pulmonary vascular resistance, a larger PA diameter, a smaller aortic diameter and pulmonary arterial hypertension associated with patent-ductus arteriosus, atrial or ventricular septal defects were significantly associated with LMCA-Co. Bare-metal stents were implanted in 12 patients and 1 patient underwent PAA and atrial septal defect surgery and another one declined LMCA stenting procedure. Conclusion Our study demonstrates that LMCA-Co is one of the most important and potentially lethal complications of severe PH, and alertness for this risk seems to be necessary in specific circumstances related with PAA. However, long-term benefit from stenting in this setting remains as a controversy. left main coronary artery , pulmonary artery aneurysm , pulmonary hypertension Introduction Pulmonary arterial hypertension (PAH) is a severely devastating disease characterized by progressive concentric remodelling of small pulmonary arteries resulting in increasing pulmonary vascular resistance (PVR) and right-sided heart failure and eventually death.1,2 Besides the well-known usual symptoms of PAH such as dyspnea, exercise intolerance, cyanosis, palpitations, syncope, and refractory edema, chest pain sometimes indistinguishable from classic angina pectoris has also been reported to occur in 7–29% of patients.1,2 Although these symptoms are usually attributed to the unmatched metabolic demands of the overloaded and hypertrophied right ventricle, recent case studies and clinical series have revealed that extrinsic compression of the left main coronary artery (LMCA) by a dilated pulmonary artery (PA) main trunk may cause angina in PAH.1–17 This causal relationship between PA enlargement and proximal LMCA compression (Co) in certain circumstances has been increasingly reported.1–17 PA aneurysm (A) has been documented in post-mortem examinations very rarely, and has been documented to occur in younger age group than those in aortic aneurysms with an equal sex incidence.18–30 Eighty-nine per cent of all PAAs have been reported to be located in the main PA, and its extension to left PA is more common than to right PA.18–20 More than half of all PAAs have been documented in patients with PAH associated with congenital heart disease (APAH-CHD).18–30 Cystic medial necrosis due to structural changes in elastin and collagen under the increased PA pressure or turbulent flow through the stenotic or abnormally opening pulmonary valve or shear stress resulting from left to right shunt flow are proposed mechanisms of transformation to PAAs.19–29 However, the incidence of LMCA-Co in PAH or other clinical forms of pulmonary hypertension (PH) remains to be established, and risk-based screening algorithms and optimal management strategies for both PAAs and LMCA-Co in these settings need to be determined.1–17 In this single-centre prospective study, we aimed to evaluate incidence, clinical, and haemodynamic correlates and management strategies of LMCA-Co in patients with PAH. Methods Our study group comprised of 269 patients (female 166, age 52.9 ± 17.3 years) out of overall 498 patients with confirmed PH (54%) who were enrolled into the single-centre, prospective and observational EvalUation of Pulmonary Hypertension Risk factors AssociaTEd with Survival (EUPHRATES) study, and underwent coronary angiography (CA) because of the PAA on echocardiography, angina or incidentally detected LMCA-Co on diagnostic evaluation with multidetector computed tomography (MDCT). The diagnostic algorithms, clinical and haemodynamic definitions and management strategies have been based on ESC/ERS 2009 PH Guidelines, and have also been revised after publication of the ESC/ERS 2015 PH Guidelines.1,2 Functional class (FC) assessment, six-minute walk distance (6MWD) and Doppler echocardiography have been routinely performed at the periodic assessments whereas repeat right heart catheterization has been performed in case of clinical worsening episodes due to PH. We defined the PAA as presence of PA diameter >30 mm on echocardiography and/or MDCT. Only femoral venous route with a 6-Fr sheath was used for right heart catheterization, and 6-Fr sheath was also used for femoral arterial access for left heart catheterization and/or CA procedures. The optimal planes to visualize the external compression and narrowing of proximal LMCA have been investigated, and the LMCA-Co was defined as the presence of diameter stenosis ≥ 50% in reference distal LMCA segment on two consecutive angiographic planes, and the take-off angle of proximal LMCA segment in reference to left sinus of Valsalva was also evaluated. The LMCA-Co and need for stenting were initially assessed from recorded CA images by two experienced interventional cardiologists who are blinded for clinical status separately, and a final consensus for optimal management strategy was achieved in all patients. The study protocol was approved by Institutional Ethics Committee, and a written informed consent was obtained from all patients. Statistical analysis Continuous variables were expressed as mean ± standard deviation or median (interquartile range) values. Categorical variables were expressed as a percentage. Student’s t-test or Mann–Whitney U test were used to compare continuous variables between the groups with and without LMCA-Co. The χ2 or Fisher’s exact test were used to compare categorical variables between these two groups. The receiver operating characteristics (ROC) curve analysis was used to demonstrate the relationship between variables and LMCA-Co in the univariate analysis. Sensitivity (Sens) and specificity (Spec) of the cut-off values of continuous variables for LMCA-Co were also evaluated. Two-tailed P-values <0.05 were considered to indicate statistical significance. Statistical analyses were performed using SPSS, version 20.0 for Windows. Results General characteristics The baseline clinical, echocardiographic and haemodynamic measures of the enrolled 269 patients are summarized in Table 1. The World Health Organisation (WHO) FC was III or IV in 90.6% of these, and median 6MWD was 270 (163–345) m. The mean diameter of PA was 35.2 ± 8.1 mm on echocardiography, and PAA as defined by the presence of PA diameter >30 mm was documented in 228 (84.8%) of 269 patients assessed by CA. Mean values of invasively evaluated PA systolic, diastolic, and mean pressures were 82 ± 29, 30 ± 16, and 50 ± 20 mm Hg, and median pulmonary and systemic vascular resistance measures were 6.2 (4.1–11.5) and 22 (16.3–26) Wood units, respectively. Angiographic findings The LMCA-Co ≥ 50% was documented in 22 (8.2%) out of the 269 patients who underwent CA, and % diameter stenosis were between 70% and 90% in 14 (64%) of these patients. The LMCA-Co was diagnosed during evaluation of PAA by MDCT prior to CA in 8 patients (Figure 1A and B). The LMCA take-off angle in reference to left sinus of Valsalva was less than 30° in all patients with LMCA-Co whereas this angle was higher than 60° in other patients without LMCA-Co. However, any narrowing in the distal LMCA segment or other segments of left and right coronary arteries was not documented. Because external compression by PAA resulted in an ovoid-shaped deformation of LMCA concomitant with narrowing of the take-off angle in reference to left sinus of Valsalva, the best plane transsecting the short axis of compressed LMCA was left anterior oblique (60°) or anterior views with or without cranial angulations (30°) while other planes transsecting the long-axis of compressed LMCA were found to miss the narrowings (Figure 2A–D). Hoarseness due to recurrent nerve compression by PAA and typical angina were noted in all patients with LMCA-Co. Figure 1 View largeDownload slide (A) Ostial eccentric left main coronary artery (LMCA) compression (red arrow) by pulmonary artery aneurysm (PAA) in a severe pulmonary hypertension is seen. (B) Ostial LMCA is compressed by PAA (yellow arrow). Figure 1 View largeDownload slide (A) Ostial eccentric left main coronary artery (LMCA) compression (red arrow) by pulmonary artery aneurysm (PAA) in a severe pulmonary hypertension is seen. (B) Ostial LMCA is compressed by PAA (yellow arrow). Figure 2 View largeDownload slide (A) The LMCA compression is evident on left anterior oblique (LAO) cranial view. White arrow indicates significant narrowing at ostial segment of LMCA. (B) Anteroposterior cranial view showing the narrowed angle of LMCA take-off in reference to aortic axis due to external compression of PAA. (C) Right anterior oblique caudal view cross-secting large diameter of stenotic LMCA segment in which significant obstruction is missed because of the slit-like nature of narrowing. (D) (LAO) caudal (spider) view showing downward displacement of ostial LMCA. This plane also transsects the long axis of slit-like segment and missed the stenosis. White arrow indicates displacement of LMCA due to pulmonary arterial compression. Figure 2 View largeDownload slide (A) The LMCA compression is evident on left anterior oblique (LAO) cranial view. White arrow indicates significant narrowing at ostial segment of LMCA. (B) Anteroposterior cranial view showing the narrowed angle of LMCA take-off in reference to aortic axis due to external compression of PAA. (C) Right anterior oblique caudal view cross-secting large diameter of stenotic LMCA segment in which significant obstruction is missed because of the slit-like nature of narrowing. (D) (LAO) caudal (spider) view showing downward displacement of ostial LMCA. This plane also transsects the long axis of slit-like segment and missed the stenosis. White arrow indicates displacement of LMCA due to pulmonary arterial compression. Correlates of extrinsic LMCA compression Univariate comparisons revealed that a younger age, a D-shaped septum, the higher PA systolic, mean and diastolic pressures and PVR, a larger PA diameter, a smaller aortic diameter and clinical diagnosis of APAH-CHD due to patent ductus arteriosus (PDA) [odds ratio (OR): 19.5, 95% confidence interval (95% CI) 6.21–61.7], atrial septal defect (ASD) (OR: 2.89, 95% CI 0.97–8.58) and ventricular septal defect (VSD) (OR: 2.89, 95% CI 0.97–8.58) were significantly associated with LMCA-Co (Table 1). The ROC analysis showed that a younger age [area under curve (AUC) 0.15, 95% CI 0.03–0.26)], a higher PA/aortic diameter ratio (AUC 0.91, 95% CI 0.85–0.96), an increased PA mean pressure (AUC 0.84, 95% CI 0.74–0.93), a larger PA diameter (AUC 0.84, 95% CI 0.75–0.93) and a higher PVR (AUC 0.70, 95% CI 0.54–0.86) predicted LMCA-Co (Table 2 and Figure 3). For LMCA-Co, diagnosis of APAH-CHD due to PDA had a Sens of 36% and a Spec of 97%, PA diameter >40.5 mm had a Sens of 82% and a Spec of 82%, PA/Aortic diameter ratio >1.24 had a Sens of 91% and a Spec of 74%, PA mean pressure >49.5 mm Hg had a Sens of 93% and a Spec of 65%, and age of younger than 43.4 years had a Sens of 14% and a Spec of 80%. Table 1 The comparison of baseline clinical, imaging and invasive haemodynamic measures between the groups Variables LMCA compression present (n = 22) LMCA compression absent (n = 247) P value Age (years) 34.6 ± 13.6 54.5 ± 16.7 <0.001 Sex (female %) 12 (54.5%) 154 (62.3%) 0.175 WHO-FC (median) 3 3 0.765 6 MWD, m (median) 286 (190–363) 268 (160–340) 0.311 PH Group (%)  Group 1 PH 19 (90.5%) 115 (48.1%) 0.003  Group 2 PH 0 13 (5.4%)  Group 3 PH 0 36 (15.1%)  Group 4 PH 2 (9.5%) 75 (31.4%) Subgroups of Group 1 PH (%)  IPAH 6 (31.6%) 51 (43.6%) 0.077  APAH-CTD 0 15 (12.8%)  APAH-CHD 13 (68.4%) 51 (43.6%) APAH-PDA (%) 8 (36.4%) 7 (2.8%) <0.001 APAH-ASD (%) 5 (23.8%) 24 (9.8%) 0.047 APAH-VSD (%) 5 (23.8%) 24 (9.8%) 0.047 Heart rate (beat per minute) 92.8 ± 16.8 87.8 ± 16.9 0.204 EF (%) 63.2 ± 3.7 61.8 ± 8.1 0.826 D-shaped septum (%) 19 (95%) 142 (64.8%) 0.023 PA diameter (mm) 46 ± 8 32 ± 7.2 <0.001 Aortic diameter (mm) 29 ± 6.7 31.2 ± 7.5 0.009 PA/aortic diameter ratio 1.62 ±0.31 1.11 ±0.25 <0.001 SBP (mmHg) 108 ± 27 124 ± 27 0.017 DBP (mmHg) 72 ± 11 72 ± 16 0.968 RA pressure (mmHg) 7.2 ± 2.3 9.5 ± 5.3 0.068 PASP (mmHg) 110 ± 24 79 ± 28 <0.001 PADP (mmHg) 49.6 ± 16 28.6 ± 15.3 <0.001 PAMP (mmHg) 72.5 ± 18.7 47.7 ± 19.3 <0.001 PVR (Wood units) 12.8 (5.9–19) 6 (4–10.8) 0.005 SVR (Wood units) 22.8 ± 7.6 22 ± 9 0.414 CO (L/min) 4.7 ± 2.2 4.6 ± 1.3 0.421 PAH targeted treatment (%)  No 3 (15.8%) 69 (29.6%) 0.287  Mono 14 (73.7%) 153 (65.7%)  Dual 2 (10.5%) 11 (4.7%) Variables LMCA compression present (n = 22) LMCA compression absent (n = 247) P value Age (years) 34.6 ± 13.6 54.5 ± 16.7 <0.001 Sex (female %) 12 (54.5%) 154 (62.3%) 0.175 WHO-FC (median) 3 3 0.765 6 MWD, m (median) 286 (190–363) 268 (160–340) 0.311 PH Group (%)  Group 1 PH 19 (90.5%) 115 (48.1%) 0.003  Group 2 PH 0 13 (5.4%)  Group 3 PH 0 36 (15.1%)  Group 4 PH 2 (9.5%) 75 (31.4%) Subgroups of Group 1 PH (%)  IPAH 6 (31.6%) 51 (43.6%) 0.077  APAH-CTD 0 15 (12.8%)  APAH-CHD 13 (68.4%) 51 (43.6%) APAH-PDA (%) 8 (36.4%) 7 (2.8%) <0.001 APAH-ASD (%) 5 (23.8%) 24 (9.8%) 0.047 APAH-VSD (%) 5 (23.8%) 24 (9.8%) 0.047 Heart rate (beat per minute) 92.8 ± 16.8 87.8 ± 16.9 0.204 EF (%) 63.2 ± 3.7 61.8 ± 8.1 0.826 D-shaped septum (%) 19 (95%) 142 (64.8%) 0.023 PA diameter (mm) 46 ± 8 32 ± 7.2 <0.001 Aortic diameter (mm) 29 ± 6.7 31.2 ± 7.5 0.009 PA/aortic diameter ratio 1.62 ±0.31 1.11 ±0.25 <0.001 SBP (mmHg) 108 ± 27 124 ± 27 0.017 DBP (mmHg) 72 ± 11 72 ± 16 0.968 RA pressure (mmHg) 7.2 ± 2.3 9.5 ± 5.3 0.068 PASP (mmHg) 110 ± 24 79 ± 28 <0.001 PADP (mmHg) 49.6 ± 16 28.6 ± 15.3 <0.001 PAMP (mmHg) 72.5 ± 18.7 47.7 ± 19.3 <0.001 PVR (Wood units) 12.8 (5.9–19) 6 (4–10.8) 0.005 SVR (Wood units) 22.8 ± 7.6 22 ± 9 0.414 CO (L/min) 4.7 ± 2.2 4.6 ± 1.3 0.421 PAH targeted treatment (%)  No 3 (15.8%) 69 (29.6%) 0.287  Mono 14 (73.7%) 153 (65.7%)  Dual 2 (10.5%) 11 (4.7%) APAH, associated pulmonary arterial hypertension; ASD, atrial septal defect; CHD, congenital heart disease; CO, cardiac output; CTD, connective tissue disease; DBP, systemic arterial diastolic blood pressure; EF %, ejection fraction%; IPAH, idiopathic pulmonary arterial hypertension; LMCA, left main coronary artery; PA, pulmonary artery; PADP, pulmonary artery diastolic pressure; PAH, pulmonary arterial hypertension; PAMP, pulmonary artery mean pressure; PASP, pulmonary artery systolic pressure; PDA, patent ductus arteriosus; PH, pulmonary hypertension; PVR, pulmonary vascular resistance; RA, right atrium; SBP, systemic arterial systolic blood pressure; SVR, systemic vascular resistance; VSD, ventricular septal defect; WHO-FC, world health organization functional class; 6MWD, six-minute walking distance. Table 1 The comparison of baseline clinical, imaging and invasive haemodynamic measures between the groups Variables LMCA compression present (n = 22) LMCA compression absent (n = 247) P value Age (years) 34.6 ± 13.6 54.5 ± 16.7 <0.001 Sex (female %) 12 (54.5%) 154 (62.3%) 0.175 WHO-FC (median) 3 3 0.765 6 MWD, m (median) 286 (190–363) 268 (160–340) 0.311 PH Group (%)  Group 1 PH 19 (90.5%) 115 (48.1%) 0.003  Group 2 PH 0 13 (5.4%)  Group 3 PH 0 36 (15.1%)  Group 4 PH 2 (9.5%) 75 (31.4%) Subgroups of Group 1 PH (%)  IPAH 6 (31.6%) 51 (43.6%) 0.077  APAH-CTD 0 15 (12.8%)  APAH-CHD 13 (68.4%) 51 (43.6%) APAH-PDA (%) 8 (36.4%) 7 (2.8%) <0.001 APAH-ASD (%) 5 (23.8%) 24 (9.8%) 0.047 APAH-VSD (%) 5 (23.8%) 24 (9.8%) 0.047 Heart rate (beat per minute) 92.8 ± 16.8 87.8 ± 16.9 0.204 EF (%) 63.2 ± 3.7 61.8 ± 8.1 0.826 D-shaped septum (%) 19 (95%) 142 (64.8%) 0.023 PA diameter (mm) 46 ± 8 32 ± 7.2 <0.001 Aortic diameter (mm) 29 ± 6.7 31.2 ± 7.5 0.009 PA/aortic diameter ratio 1.62 ±0.31 1.11 ±0.25 <0.001 SBP (mmHg) 108 ± 27 124 ± 27 0.017 DBP (mmHg) 72 ± 11 72 ± 16 0.968 RA pressure (mmHg) 7.2 ± 2.3 9.5 ± 5.3 0.068 PASP (mmHg) 110 ± 24 79 ± 28 <0.001 PADP (mmHg) 49.6 ± 16 28.6 ± 15.3 <0.001 PAMP (mmHg) 72.5 ± 18.7 47.7 ± 19.3 <0.001 PVR (Wood units) 12.8 (5.9–19) 6 (4–10.8) 0.005 SVR (Wood units) 22.8 ± 7.6 22 ± 9 0.414 CO (L/min) 4.7 ± 2.2 4.6 ± 1.3 0.421 PAH targeted treatment (%)  No 3 (15.8%) 69 (29.6%) 0.287  Mono 14 (73.7%) 153 (65.7%)  Dual 2 (10.5%) 11 (4.7%) Variables LMCA compression present (n = 22) LMCA compression absent (n = 247) P value Age (years) 34.6 ± 13.6 54.5 ± 16.7 <0.001 Sex (female %) 12 (54.5%) 154 (62.3%) 0.175 WHO-FC (median) 3 3 0.765 6 MWD, m (median) 286 (190–363) 268 (160–340) 0.311 PH Group (%)  Group 1 PH 19 (90.5%) 115 (48.1%) 0.003  Group 2 PH 0 13 (5.4%)  Group 3 PH 0 36 (15.1%)  Group 4 PH 2 (9.5%) 75 (31.4%) Subgroups of Group 1 PH (%)  IPAH 6 (31.6%) 51 (43.6%) 0.077  APAH-CTD 0 15 (12.8%)  APAH-CHD 13 (68.4%) 51 (43.6%) APAH-PDA (%) 8 (36.4%) 7 (2.8%) <0.001 APAH-ASD (%) 5 (23.8%) 24 (9.8%) 0.047 APAH-VSD (%) 5 (23.8%) 24 (9.8%) 0.047 Heart rate (beat per minute) 92.8 ± 16.8 87.8 ± 16.9 0.204 EF (%) 63.2 ± 3.7 61.8 ± 8.1 0.826 D-shaped septum (%) 19 (95%) 142 (64.8%) 0.023 PA diameter (mm) 46 ± 8 32 ± 7.2 <0.001 Aortic diameter (mm) 29 ± 6.7 31.2 ± 7.5 0.009 PA/aortic diameter ratio 1.62 ±0.31 1.11 ±0.25 <0.001 SBP (mmHg) 108 ± 27 124 ± 27 0.017 DBP (mmHg) 72 ± 11 72 ± 16 0.968 RA pressure (mmHg) 7.2 ± 2.3 9.5 ± 5.3 0.068 PASP (mmHg) 110 ± 24 79 ± 28 <0.001 PADP (mmHg) 49.6 ± 16 28.6 ± 15.3 <0.001 PAMP (mmHg) 72.5 ± 18.7 47.7 ± 19.3 <0.001 PVR (Wood units) 12.8 (5.9–19) 6 (4–10.8) 0.005 SVR (Wood units) 22.8 ± 7.6 22 ± 9 0.414 CO (L/min) 4.7 ± 2.2 4.6 ± 1.3 0.421 PAH targeted treatment (%)  No 3 (15.8%) 69 (29.6%) 0.287  Mono 14 (73.7%) 153 (65.7%)  Dual 2 (10.5%) 11 (4.7%) APAH, associated pulmonary arterial hypertension; ASD, atrial septal defect; CHD, congenital heart disease; CO, cardiac output; CTD, connective tissue disease; DBP, systemic arterial diastolic blood pressure; EF %, ejection fraction%; IPAH, idiopathic pulmonary arterial hypertension; LMCA, left main coronary artery; PA, pulmonary artery; PADP, pulmonary artery diastolic pressure; PAH, pulmonary arterial hypertension; PAMP, pulmonary artery mean pressure; PASP, pulmonary artery systolic pressure; PDA, patent ductus arteriosus; PH, pulmonary hypertension; PVR, pulmonary vascular resistance; RA, right atrium; SBP, systemic arterial systolic blood pressure; SVR, systemic vascular resistance; VSD, ventricular septal defect; WHO-FC, world health organization functional class; 6MWD, six-minute walking distance. Table 2 ROC curves, sensitivity, and specificity of the measures for prediction of LMCA compression Measures (cut-off values) AUC 95% CI Sensitivity Specificity P-value PA diameter (>40.5 mm) 0.842 0.751–0.934 92 82 <0.001 Aortic diameter (<35 mm) 0.275 0.116–0.435 14 75 0.006 PA/Aortic diameter ratio (>1.24) 0.916 0.854–0.978 91 74 <0.001 PVR (>8.8 Wood unit) 0.704 0.544–0.864 71 68 0.013 PASP (>76.5 mm Hg) 0.820 0.710–0.929 78 56 <0.001 PAMP (>49.5 mm Hg) 0.841 0.744–0.942 93 65 <0.001 PADP (>36.5 mm Hg) 0.843 0.750–0.933 78 82 <0.001 Age (<43, 4 years) 0.151 0.041–0.262 14 80 <0.001 Measures (cut-off values) AUC 95% CI Sensitivity Specificity P-value PA diameter (>40.5 mm) 0.842 0.751–0.934 92 82 <0.001 Aortic diameter (<35 mm) 0.275 0.116–0.435 14 75 0.006 PA/Aortic diameter ratio (>1.24) 0.916 0.854–0.978 91 74 <0.001 PVR (>8.8 Wood unit) 0.704 0.544–0.864 71 68 0.013 PASP (>76.5 mm Hg) 0.820 0.710–0.929 78 56 <0.001 PAMP (>49.5 mm Hg) 0.841 0.744–0.942 93 65 <0.001 PADP (>36.5 mm Hg) 0.843 0.750–0.933 78 82 <0.001 Age (<43, 4 years) 0.151 0.041–0.262 14 80 <0.001 AUC, area under curve; CI, confidence interval; LMCA, left main coronary artery; PA, pulmonary artery; PADP, pulmonary artery diastolic pressure; PAMP, pulmonary artery mean pressure; PASP, pulmonary artery systolic pressure; PVR, pulmonary vascular resistance. Table 2 ROC curves, sensitivity, and specificity of the measures for prediction of LMCA compression Measures (cut-off values) AUC 95% CI Sensitivity Specificity P-value PA diameter (>40.5 mm) 0.842 0.751–0.934 92 82 <0.001 Aortic diameter (<35 mm) 0.275 0.116–0.435 14 75 0.006 PA/Aortic diameter ratio (>1.24) 0.916 0.854–0.978 91 74 <0.001 PVR (>8.8 Wood unit) 0.704 0.544–0.864 71 68 0.013 PASP (>76.5 mm Hg) 0.820 0.710–0.929 78 56 <0.001 PAMP (>49.5 mm Hg) 0.841 0.744–0.942 93 65 <0.001 PADP (>36.5 mm Hg) 0.843 0.750–0.933 78 82 <0.001 Age (<43, 4 years) 0.151 0.041–0.262 14 80 <0.001 Measures (cut-off values) AUC 95% CI Sensitivity Specificity P-value PA diameter (>40.5 mm) 0.842 0.751–0.934 92 82 <0.001 Aortic diameter (<35 mm) 0.275 0.116–0.435 14 75 0.006 PA/Aortic diameter ratio (>1.24) 0.916 0.854–0.978 91 74 <0.001 PVR (>8.8 Wood unit) 0.704 0.544–0.864 71 68 0.013 PASP (>76.5 mm Hg) 0.820 0.710–0.929 78 56 <0.001 PAMP (>49.5 mm Hg) 0.841 0.744–0.942 93 65 <0.001 PADP (>36.5 mm Hg) 0.843 0.750–0.933 78 82 <0.001 Age (<43, 4 years) 0.151 0.041–0.262 14 80 <0.001 AUC, area under curve; CI, confidence interval; LMCA, left main coronary artery; PA, pulmonary artery; PADP, pulmonary artery diastolic pressure; PAMP, pulmonary artery mean pressure; PASP, pulmonary artery systolic pressure; PVR, pulmonary vascular resistance. Figure 3 View largeDownload slide Receiver-operating characteristics (ROC) curves of variables for prediction of LMCA compression. AO, aortae; PAPM, pulmonary arterial mean pressure. Figure 3 View largeDownload slide Receiver-operating characteristics (ROC) curves of variables for prediction of LMCA compression. AO, aortae; PAPM, pulmonary arterial mean pressure. Management of LMCA compression In patients with LMCA-Co >70% as assessed by diameter stenosis, bare-metal stents were implanted in 12 symptomatic patients (54.5%) without complication (Figure 4A–C). The median diameter and length of bare-metal stents were 4.2 mm (3.5–5.0), and 12.5 mm,9–20 respectively. One patient underwent reconstructive PA surgery and ASD repair because of mild PAH and a low PVR. Another patient declined the LMCA stenting procedure. Figure 4 View largeDownload slide (A) Left anterior oblique (LAO) cranial view of severe LMCA stenosis before stent implantation. (B) The LAO cranial view showing widening the LMCA take-off angle during full expansion of stent. (C) The LAO cranial view of LMCA immediately after stent implantation. Please note the widened angle of LMCA take-off with disappearance of ostial stenosis. Figure 4 View largeDownload slide (A) Left anterior oblique (LAO) cranial view of severe LMCA stenosis before stent implantation. (B) The LAO cranial view showing widening the LMCA take-off angle during full expansion of stent. (C) The LAO cranial view of LMCA immediately after stent implantation. Please note the widened angle of LMCA take-off with disappearance of ostial stenosis. In-hospital and post-discharge clinical course A non-sudden cardiac death was observed on 10th day of LMCA stenting in one patient with severely compromised cardiac haemodynamics prior to stenting which remains unresponsive to subsequent treatments. During regular post-discharge follow-up period of median 17.3 months no death was documented. Discussion In this single-centre study based on large series of patients with PH, LMCA-Co ≥ 50% was documented in 8.2% patients who underwent CA, and % diameter stenosis ranged between 70% and 90% in the majority of these patients. Hoarseness due to recurrent nerve compression and angina were noted in all patients with LMCA-Co. A younger age, a D-shaped septum, a higher PA systolic, mean and diastolic, pressures and PVR, a larger PA diameter with a smaller aortic diameter and clinical diagnosis of APAH-CHD due to PDA, ASD or VSD were significantly associated with LMCA-Co. The APAH due to PDA was the most powerful risk factor of LMCA-Co followed by a younger age, an increasing PA mean pressure, PA diameter, and PVR as the correlates of LMCA-Co. Bare-metal stents were implanted in 54.5% of these patients, and one patient underwent reconstructive PA surgery with ASD repair. Proximal LMCA-Co by a PAA was first described as a complication of severe PH 60 years ago.3 Moreover, other situations resulting in PAA have also been documented to cause LMCA-Co.3–17 The majority of the data concerning LMCA stenting in this setting have been based on case reports or small series.7,8,13–17 Cardiac MDCT provides a comprehensive method to evaluate the severity of extrinsic LMCA-Co, the angulation of this vessel relative to the left sinus of Valsalva, the underlying pathology of PAA, and left and right ventricular functions.7,9,13–17 The degree of compression, a LMCA angle of take-off from the left sinus of Valsalva of <30% and a main PA/aorta diameter ratio >2.0 have been reported to increase the risk for LMCA-Co.7–17 In the ever largest series of Galie et al.16 in which LMCA deformation patterns and management strategies were evaluated, 121 out of the 765 (15.8%) patients with PAH underwent MDCT because of their angina or angina-like symptoms. Four MDCT patterns described were as follows; (i) LMCA-Co, (ii) LMCA dislocation (a take-off angle <60° without compression), (iii) close proximity (PA to LMCA distance <1 mm, and (iv) normal pattern (PA to LMCA distance >1 mm). The MDCT evaluation showed LMCA–Co, LMCA dislocation and close proximity patterns in 28.9%, 40.5% and 8.3% of the patients, respectively.16 Patients with first three patterns underwent selective CA, and LMCA–Co ≥ 50% was diagnosed in 39, 7% of those with angina or angina-like chest pain. In other words, LMCA-Co was documented in 6% of the overall PH patients. Main PA diameter >40 mm as assessed by MDCT was found to predict LMCA-Co ≥ 50%, and angiographic LMCA-Co ≥ 50% was diagnosed in 10%, 30, 6%, and 91, 4% of the proximity, dislocation and compression patterns of MDCT, respectively.16 The LMCA-Co ≥ 50% was noted in 8.2% of our patients who underwent CA, and 4.4% of overall PH patients. The LMCA-Co has been reported to be associated with PA diameter and PA diameter/aortic diameter ratio, but not with the severity of PAH in two large PAH series.13,16 In contrast to these series, we found that not only PA diameter and PA diameter/aortic diameter ratio, but also clinical etiology of PDA, a younger age, and severity of PAH as defined by higher PA mean pressure and PVR predicted the risk of LMCA-Co. We also found that LMCA take-off angle in reference to left sinus of Valsalva was lower than 30° in all patients with LMCA-Co. However, neither the optimal treatment of PAA, nor management of LMCA-Co have been standardized. Because of the risk of PAA dissection and rupture, an aggressive surgical approach has been advocated for patients with PH.18–24,27–30 Although there is no evidence-based consensus for surgery, adults with main PAA diameter >5.5 cm, ≥5 mm increase in the diameter of the PAA in 6 months, clinical symptoms, co-existing severe valvular pathologies or shunt flow, and verification of extrinsic compression of LMCA or adjacent structures, thrombus formation in the PAA are considered as indications for surgery.18–30 On the other hand, patients with PH may have a high surgical risk and may need a heart-lung transplantation.18–28 The LMCA stenting with encouraging angiographic results and satisfactory short-term clinical outcomes has been developed as the revascularization strategy of choice, and compression of the ostial or proximal part of this artery, sparing the LMCA bifurcation permits a single stent placement.7–17 In the large series of Galie et al.16 85.4% of patients with LMCA stenosis >50% underwent LMCA stenting whereas both the rate of LMCA-Co and the LMCA stenting were lower in our study group. Moreover, in contrast to 48.9% rate of drug eluting stent placement in the series of Galie et al.,16 only bare metal stents were used for LMCA-Co treatment in our study. Because of the large diameters of LMCA, benefit of drug eluting stents in this setting has remained unproven whereas durability of radial force against extrinsic compression is a major challenge.16,17 Long-term follow-up data of these patients after LMCA stenting suggest a favourable clinical outcome despite the presence of a trend for statistically significant re-narrowing of the LMCA after stenting.16 This implies the ongoing risk for progressive compression of LMCA by enlarged and overloaded PAs.16,17 Galie et al.16 reported that the rates for death or double-lung transplant and rates for death, double-lung transplant, or restenosis of patients undergoing stenting or PA surgical plasty for LMCA-Co were 5% and 30% at 3 years, respectively. Except one in-hospital death seeming to be associated with underlying heart failure, we documented no death during follow-up of period. The selection of best methods for adjunctive periprocedural imaging and physiologic assessment in this patients is another concern.17,31 Intravascular ultrasound with or without pressure wire can also be used as a guidance method to evaluate the LMCA-Co and to assess optimal stent sizing, deployment and apposition during stenting.31 Because of the ostial location of the LMCA segment to be stented, the risk of stent displacement to the aorta is another critical issue.32 Moreover, long-term antiplatelet management after LMCA stenting is another controversy in these patients. Limitations The absence of the detailed MDCT morphologic definition which may be predictive for LMCA-Co patterns, and quantitative assessment of flow obliteration in the presence of ovoid-shaped lumen with currently available methods such as intravascular ultrasound or fractional flow reserve in the decision making for management strategy may be considered as important limitations. The durability of the radial force of bare metal stents against progressive extrinsic compression due to increasing PA pressures is another concern. The long-term prospective randomized studies seem to be needed to evaluate whether LMCA stenting provides any additive benefit beyond the targeted PH treatments in this setting. Moreover, because of the too small size of the subgroup of patients with significant LMCA-Co, the multiple linear regression analysis that could be very important to evaluate the independent roles of different determinants on the genesis this complication was not possible. Accordingly, this issue remains as an important limitation of this study, and description of the findings should be less absolute since ROC analysis per se cannot be conclusive. Conclusions We demonstrate that LMCA-Co is the one of the most important complications of severe PAH, and alertness for this risk seems to be necessary in younger patients and in specific circumstances related with PAA including PDA and haemodynamically severe pulmonary vascular diseases. However, long-term benefit from LMCA stenting in this setting remains as a controversy. Acknowledgements The authors thank www.metastata.com for their contributions to statistical analysis and trial design. Conflict of interest: None declared. References 1 Galiè N , Hoeper MM , Humbert M , Torbicki A , Vachiery JL , Barbera JA ; ESC Committee for Practice Guidelines (CPG) . Guidelines for the diagnosis and treatment of pulmonary hypertension: the task force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT) . Eur Heart J 2009 ; 30 : 2493 – 537 . Google Scholar CrossRef Search ADS PubMed 2 Galie` N , Humbert M , Vachiery JL , Gibbs S , Lang I , Torbicki A. 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension the joint task force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS) . Eur Respir J 2015 ; 46 : 903 – 75 . Google Scholar CrossRef Search ADS PubMed 3 Corday E , Gold H , Kaplan L. Coronary artery compression: an explanation for the cause of coronary insufficiency in pulmonary hypertension . Trans Am Coll Cardiol 1957 ; 7 : 93 – 103 . Google Scholar PubMed 4 Kajita LJ , Martinez EE , Ambrose JA , Lemos PA , Esteves A , Nogueira da Gama M et al. Extrinsic compression of the left main coronary artery by a dilated pulmonary artery: clinical, angiographic, and hemodynamic determinants . Catheter Cardiovasc Interv 2001 ; 52 : 49 – 54 . http://dx.doi.org/10.1002/1522-726X(200101)52:1<49::AID-CCD1012>3.0.CO;2-0 Google Scholar CrossRef Search ADS PubMed 5 Gómez A , Bialostozky D , Zajarias A , Santos E , Palomar A , Martínez ML et al. Right ventricular ischemia in patients with primary pulmonary hypertension . J Am Coll Cardiol 2001 ; 38 : 1137 – 42 . Google Scholar CrossRef Search ADS PubMed 6 de Jesus Perez VA , Haddad F , Vagelos RH , Fearon W , Feinstein J , Zamanian RT. Angina associated with left main coronary artery compression in pulmonary hypertension . J Heart Lung Transplant 2009 ; 28 : 527 – 30 . Google Scholar CrossRef Search ADS PubMed 7 Rich S , McLaughlin VV , O’Neill W. Stenting to reverse leftventricular ischemia due to left main coronary artery compression in primary pulmonary hypertension . Chest 2001 ; 120 : 1412 – 5 . Google Scholar CrossRef Search ADS PubMed 8 Mesquita SMF , Castro CRP , Ikari NM , Oliveira SA , Lopes AA. Likelihood of left main coronary artery compression based on pulmonary trunk diameter in patients with pulmonary hypertension . Am J Med 2004 ; 116 : 369 – 74 . Google Scholar CrossRef Search ADS PubMed 9 Dodd JD , Maree A , Palacios I , de Moor MM , Mooyaart EA , Shapiro MD. Images in cardiovascular medicine: left main coronary artery compression syndrome; evaluation with 64-slice cardiac multidetector computed tomography . Circulation 2007 ; 115 : e7 – 8 . Google Scholar CrossRef Search ADS PubMed 10 Dubois CL , Dymarkowski S , Van Cleemput J. Compression of the left main pulmonary artery in a patient with the Eisenmenger syndrome . Eur Heart J 2007 ; 28 : 1945. http://dx.doi.org/10.1093/eurheartj/ehl556 Google Scholar CrossRef Search ADS PubMed 11 Vaseghi M , Lee JS , Currier JW. Acute myocardial infarction secondary to left main coronary artery compression by pulmonary artery aneurysm in pulmonary arterial hypertension . J Invasive Cardiol 2007 ; 19 : E375 – 7 . Google Scholar PubMed 12 Lindsey JB , Brilakis ES , Banerjee S. Acute coronary syndrome due to extrinsic compression of the left main coronary artery in a patient with severe pulmonary hypertension: successful treatment with percutaneous coronary intervention . Cardiovasc Revasc Med 2008 ; 9 : 47 – 51 . http://dx.doi.org/10.1016/j.carrev.2007.07.003 Google Scholar CrossRef Search ADS PubMed 13 Lee MS , Oyama J , Bhatia R , Kim YH , Park SJ. Left main coronary artery compression from pulmonary enlargement due to pulmonary hypertension: a contemporary review and arguments for percutaneous revascularization . Catheter Cardiovasc Intervent 2010 ; 76 : 543 – 50 . http://dx.doi.org/10.1002/ccd.22592 Google Scholar CrossRef Search ADS 14 Yeh DD , Ghoshhajra B , Inglessis-Azuaje I , MacGillivray T , Liberthson R , Bhatt AB. Massive pulmonary artery aneurysm causing left main coronary artery compression in the absence of pulmonary hypertension . Tex Heart Inst J 2015 ; 42 : 465 – 7 . Google Scholar CrossRef Search ADS PubMed 15 Ihdayhid AR , Asrar Ul Haq M , Dembo L , Yong G. Simultaneous coronary and pulmonary angiography to diagnose critical left main coronary artery stenosis secondary to dilated pulmonary artery . J Am Coll Cardiol Intervention 2016 ; 9 : 1193 – 4 . http://dx.doi.org/10.1016/j.jcin.2016.03.034 Google Scholar CrossRef Search ADS 16 Galiè N , Saia F , Palazzini M , Manes A , Russo V , Bacchi Reggiani ML et al. Left main coronary artery compression in patients with pulmonary arterial hypertension and angina . J Am Coll Cardiol 2017 ; 69 : 2808 – 17 . Google Scholar CrossRef Search ADS PubMed 17 Alfonso F , Rivero F. MD Left main coronary artery compression in patients with pulmonary arterial hypertension . J Am Coll Cardiol 2017 ; 69 : 2818 – 20 . http://dx.doi.org/10.1016/j.jacc.2017.04.047 Google Scholar CrossRef Search ADS PubMed 18 Blades B , Ford W , Clark P. Pulmonary artery aneurysms: report of a case treated by surgical intervention . Circulation 1950 ; 2 : 565 – 71 . http://dx.doi.org/10.1161/01.CIR.2.4.565 Google Scholar CrossRef Search ADS PubMed 19 Metras D , Ouattara K , Quezzin-Coulibaly A. Aneurysm of the pulmonary artery with cystic medial necrosis and massive pulmonary valvular insufficiency: report of two successful surgical cases . Eur J Cardiothorac Surg 1987 ; 1 : 119 – 24 . http://dx.doi.org/10.1016/1010-7940(87)90023-6 Google Scholar CrossRef Search ADS PubMed 20 Veldtman GR , Dearani JA , Warnes CA. Low pressure giant pulmonary artery aneurysms in the adult: natural history and management strategies . Heart 2003 ; 89 : 1067 – 70 . http://dx.doi.org/10.1136/heart.89.9.1067 Google Scholar CrossRef Search ADS PubMed 21 Smalcelj A , Brida V , Samarzija M , Matana A , Margetic E , Drinkovic N. Giant, dissecting, high-pressure pulmonary artery aneurysm: case report of a 1-year natural course . Tex Heart Inst J 2005 ; 32 : 589 – 94 . Google Scholar PubMed 22 Sakuma M , Demachi J , Suzuki J , Nawata J , Takahashi T , Shirato K. Proximal pulmonary artery aneurysm in patients with pulmonary artery hypertension: complicated cases . Intern Med 2007 ; 46 : 1789 – 93 . Google Scholar CrossRef Search ADS PubMed 23 Nguyen ET , Silva CI , Seely JM , Chong S , Lee KS , Müller NL. Pulmonary artery aneurysms and pseudoaneurysms in adults: findings at CT and radiography . AJR Am J Roentgenol 2007 ; 188 : W126 – 34 . Google Scholar CrossRef Search ADS PubMed 24 Vistarini N , Auber S , Gandjbakhch I , Pavie A. Surgical treatment of a pulmonary artery aneurysm . Eu J Cardiothorac Surg 2007 ; 31 : 3: 1139 – 41 . 25 Boerrigter B , Mauritz G-J , Marcus JT , Helderman F , Postmus PE , Westerhof N et al. Progressive dilatation of the main pulmonary artery is a characteristic of pulmonary arterial hypertension and is not related to changes in pressure . Chest 2010 ; 138 : 1395 – 401 . Google Scholar CrossRef Search ADS PubMed 26 Shankarappa RK , Moorthy N , Chandrasekaran D , Nanjappa MC. Giant pulmonary artery aneurysm secondary to primary pulmonary hypertension . Tex Heart Inst J 2010 ; 37 : 244 – 5 . Google Scholar PubMed 27 Seguchi M , Wada H , Sakakura K , Kubo N , Ikeda N , Sugawara Y et al. Idiopathic pulmonary artery aneurysm . Circulation 2011 ; 124 : e 396 – 70 . Google Scholar CrossRef Search ADS 28 Puri D , Kaur HP , Brar R , Singh KP , Sahoo M , Mahant TS. Ruptured pulmonary artery aneurysm: a surgical emergency . Asian Cardiovasc Thorac Ann 2011 ; 19 : 436 – 9 . Google Scholar CrossRef Search ADS PubMed 29 Kreibich M , Siepe M , Kroll J , Höhn R , Grohmann J , Beyersdorf F. Aneurysms of the pulmonary artery . Circulation 2015 ; 131 : 310 – 6 . Google Scholar CrossRef Search ADS PubMed 30 Lee SE , An HY , Im JH , Sung JM , Cho IJ , Shim CY et al. Screening of mechanical complications of dilated pulmonary artery related to the risk for sudden cardiac death in patients with pulmonary arterial hypertension by transthoracic echocardiography . J Am Soc Echocardiogr 2016 ; 29 : 561 – 6 . http://dx.doi.org/10.1016/j.echo.2016.02.002 Google Scholar CrossRef Search ADS PubMed 31 Piña Y , Exaire JE , Sandoval J. Left main coronary artery extrinsic compression syndrome: combined intravascular ultrasound and pressure wire . J Invasive Cardiol 2006 ; 18 : e102 – 4 . Google Scholar PubMed 32 Adigopula S , Nsair A. Left main coronary artery stent migration . N Engl J Med 2015 ; 373 : 1957. http://dx.doi.org/10.1056/NEJMicm1500200 Google Scholar CrossRef Search ADS PubMed Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Heart Journal – Cardiovascular Imaging Oxford University Press

Extrinsic compression of left main coronary artery by aneurysmal pulmonary artery in severe pulmonary hypertension: its correlates, clinical impact, and management strategies

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Abstract

Abstract Aims Although left main coronary artery (LMCA) compression (Co) by pulmonary artery (PA) aneurysm (A) has been reported in some pulmonary hypertension (PH) series, clinical importance and management of this complication remain to be determined. In this single-centre prospective study, we evaluated correlates, clinical impact, and management strategies of LMCA-Co in patients with PH. Methods and results Our study group comprised 269 (female 166, age 52.9 ± 17.3 years) out of 498 patients with confirmed PH who underwent coronary angiography (CA) because of the PAA on echocardiography, angina or incidentally detected LMCA-Co during diagnostic evaluation with multidetector computed tomography. The LMCA-Co ≥ 50% was documented in 22 patients (8.2%) who underwent CA, and stenosis were between 70% and 90% in 14 of these. Univariate comparisons revealed that a younger age, a D-shaped septum, a higher PA systolic, diastolic, and mean pressures and pulmonary vascular resistance, a larger PA diameter, a smaller aortic diameter and pulmonary arterial hypertension associated with patent-ductus arteriosus, atrial or ventricular septal defects were significantly associated with LMCA-Co. Bare-metal stents were implanted in 12 patients and 1 patient underwent PAA and atrial septal defect surgery and another one declined LMCA stenting procedure. Conclusion Our study demonstrates that LMCA-Co is one of the most important and potentially lethal complications of severe PH, and alertness for this risk seems to be necessary in specific circumstances related with PAA. However, long-term benefit from stenting in this setting remains as a controversy. left main coronary artery , pulmonary artery aneurysm , pulmonary hypertension Introduction Pulmonary arterial hypertension (PAH) is a severely devastating disease characterized by progressive concentric remodelling of small pulmonary arteries resulting in increasing pulmonary vascular resistance (PVR) and right-sided heart failure and eventually death.1,2 Besides the well-known usual symptoms of PAH such as dyspnea, exercise intolerance, cyanosis, palpitations, syncope, and refractory edema, chest pain sometimes indistinguishable from classic angina pectoris has also been reported to occur in 7–29% of patients.1,2 Although these symptoms are usually attributed to the unmatched metabolic demands of the overloaded and hypertrophied right ventricle, recent case studies and clinical series have revealed that extrinsic compression of the left main coronary artery (LMCA) by a dilated pulmonary artery (PA) main trunk may cause angina in PAH.1–17 This causal relationship between PA enlargement and proximal LMCA compression (Co) in certain circumstances has been increasingly reported.1–17 PA aneurysm (A) has been documented in post-mortem examinations very rarely, and has been documented to occur in younger age group than those in aortic aneurysms with an equal sex incidence.18–30 Eighty-nine per cent of all PAAs have been reported to be located in the main PA, and its extension to left PA is more common than to right PA.18–20 More than half of all PAAs have been documented in patients with PAH associated with congenital heart disease (APAH-CHD).18–30 Cystic medial necrosis due to structural changes in elastin and collagen under the increased PA pressure or turbulent flow through the stenotic or abnormally opening pulmonary valve or shear stress resulting from left to right shunt flow are proposed mechanisms of transformation to PAAs.19–29 However, the incidence of LMCA-Co in PAH or other clinical forms of pulmonary hypertension (PH) remains to be established, and risk-based screening algorithms and optimal management strategies for both PAAs and LMCA-Co in these settings need to be determined.1–17 In this single-centre prospective study, we aimed to evaluate incidence, clinical, and haemodynamic correlates and management strategies of LMCA-Co in patients with PAH. Methods Our study group comprised of 269 patients (female 166, age 52.9 ± 17.3 years) out of overall 498 patients with confirmed PH (54%) who were enrolled into the single-centre, prospective and observational EvalUation of Pulmonary Hypertension Risk factors AssociaTEd with Survival (EUPHRATES) study, and underwent coronary angiography (CA) because of the PAA on echocardiography, angina or incidentally detected LMCA-Co on diagnostic evaluation with multidetector computed tomography (MDCT). The diagnostic algorithms, clinical and haemodynamic definitions and management strategies have been based on ESC/ERS 2009 PH Guidelines, and have also been revised after publication of the ESC/ERS 2015 PH Guidelines.1,2 Functional class (FC) assessment, six-minute walk distance (6MWD) and Doppler echocardiography have been routinely performed at the periodic assessments whereas repeat right heart catheterization has been performed in case of clinical worsening episodes due to PH. We defined the PAA as presence of PA diameter >30 mm on echocardiography and/or MDCT. Only femoral venous route with a 6-Fr sheath was used for right heart catheterization, and 6-Fr sheath was also used for femoral arterial access for left heart catheterization and/or CA procedures. The optimal planes to visualize the external compression and narrowing of proximal LMCA have been investigated, and the LMCA-Co was defined as the presence of diameter stenosis ≥ 50% in reference distal LMCA segment on two consecutive angiographic planes, and the take-off angle of proximal LMCA segment in reference to left sinus of Valsalva was also evaluated. The LMCA-Co and need for stenting were initially assessed from recorded CA images by two experienced interventional cardiologists who are blinded for clinical status separately, and a final consensus for optimal management strategy was achieved in all patients. The study protocol was approved by Institutional Ethics Committee, and a written informed consent was obtained from all patients. Statistical analysis Continuous variables were expressed as mean ± standard deviation or median (interquartile range) values. Categorical variables were expressed as a percentage. Student’s t-test or Mann–Whitney U test were used to compare continuous variables between the groups with and without LMCA-Co. The χ2 or Fisher’s exact test were used to compare categorical variables between these two groups. The receiver operating characteristics (ROC) curve analysis was used to demonstrate the relationship between variables and LMCA-Co in the univariate analysis. Sensitivity (Sens) and specificity (Spec) of the cut-off values of continuous variables for LMCA-Co were also evaluated. Two-tailed P-values <0.05 were considered to indicate statistical significance. Statistical analyses were performed using SPSS, version 20.0 for Windows. Results General characteristics The baseline clinical, echocardiographic and haemodynamic measures of the enrolled 269 patients are summarized in Table 1. The World Health Organisation (WHO) FC was III or IV in 90.6% of these, and median 6MWD was 270 (163–345) m. The mean diameter of PA was 35.2 ± 8.1 mm on echocardiography, and PAA as defined by the presence of PA diameter >30 mm was documented in 228 (84.8%) of 269 patients assessed by CA. Mean values of invasively evaluated PA systolic, diastolic, and mean pressures were 82 ± 29, 30 ± 16, and 50 ± 20 mm Hg, and median pulmonary and systemic vascular resistance measures were 6.2 (4.1–11.5) and 22 (16.3–26) Wood units, respectively. Angiographic findings The LMCA-Co ≥ 50% was documented in 22 (8.2%) out of the 269 patients who underwent CA, and % diameter stenosis were between 70% and 90% in 14 (64%) of these patients. The LMCA-Co was diagnosed during evaluation of PAA by MDCT prior to CA in 8 patients (Figure 1A and B). The LMCA take-off angle in reference to left sinus of Valsalva was less than 30° in all patients with LMCA-Co whereas this angle was higher than 60° in other patients without LMCA-Co. However, any narrowing in the distal LMCA segment or other segments of left and right coronary arteries was not documented. Because external compression by PAA resulted in an ovoid-shaped deformation of LMCA concomitant with narrowing of the take-off angle in reference to left sinus of Valsalva, the best plane transsecting the short axis of compressed LMCA was left anterior oblique (60°) or anterior views with or without cranial angulations (30°) while other planes transsecting the long-axis of compressed LMCA were found to miss the narrowings (Figure 2A–D). Hoarseness due to recurrent nerve compression by PAA and typical angina were noted in all patients with LMCA-Co. Figure 1 View largeDownload slide (A) Ostial eccentric left main coronary artery (LMCA) compression (red arrow) by pulmonary artery aneurysm (PAA) in a severe pulmonary hypertension is seen. (B) Ostial LMCA is compressed by PAA (yellow arrow). Figure 1 View largeDownload slide (A) Ostial eccentric left main coronary artery (LMCA) compression (red arrow) by pulmonary artery aneurysm (PAA) in a severe pulmonary hypertension is seen. (B) Ostial LMCA is compressed by PAA (yellow arrow). Figure 2 View largeDownload slide (A) The LMCA compression is evident on left anterior oblique (LAO) cranial view. White arrow indicates significant narrowing at ostial segment of LMCA. (B) Anteroposterior cranial view showing the narrowed angle of LMCA take-off in reference to aortic axis due to external compression of PAA. (C) Right anterior oblique caudal view cross-secting large diameter of stenotic LMCA segment in which significant obstruction is missed because of the slit-like nature of narrowing. (D) (LAO) caudal (spider) view showing downward displacement of ostial LMCA. This plane also transsects the long axis of slit-like segment and missed the stenosis. White arrow indicates displacement of LMCA due to pulmonary arterial compression. Figure 2 View largeDownload slide (A) The LMCA compression is evident on left anterior oblique (LAO) cranial view. White arrow indicates significant narrowing at ostial segment of LMCA. (B) Anteroposterior cranial view showing the narrowed angle of LMCA take-off in reference to aortic axis due to external compression of PAA. (C) Right anterior oblique caudal view cross-secting large diameter of stenotic LMCA segment in which significant obstruction is missed because of the slit-like nature of narrowing. (D) (LAO) caudal (spider) view showing downward displacement of ostial LMCA. This plane also transsects the long axis of slit-like segment and missed the stenosis. White arrow indicates displacement of LMCA due to pulmonary arterial compression. Correlates of extrinsic LMCA compression Univariate comparisons revealed that a younger age, a D-shaped septum, the higher PA systolic, mean and diastolic pressures and PVR, a larger PA diameter, a smaller aortic diameter and clinical diagnosis of APAH-CHD due to patent ductus arteriosus (PDA) [odds ratio (OR): 19.5, 95% confidence interval (95% CI) 6.21–61.7], atrial septal defect (ASD) (OR: 2.89, 95% CI 0.97–8.58) and ventricular septal defect (VSD) (OR: 2.89, 95% CI 0.97–8.58) were significantly associated with LMCA-Co (Table 1). The ROC analysis showed that a younger age [area under curve (AUC) 0.15, 95% CI 0.03–0.26)], a higher PA/aortic diameter ratio (AUC 0.91, 95% CI 0.85–0.96), an increased PA mean pressure (AUC 0.84, 95% CI 0.74–0.93), a larger PA diameter (AUC 0.84, 95% CI 0.75–0.93) and a higher PVR (AUC 0.70, 95% CI 0.54–0.86) predicted LMCA-Co (Table 2 and Figure 3). For LMCA-Co, diagnosis of APAH-CHD due to PDA had a Sens of 36% and a Spec of 97%, PA diameter >40.5 mm had a Sens of 82% and a Spec of 82%, PA/Aortic diameter ratio >1.24 had a Sens of 91% and a Spec of 74%, PA mean pressure >49.5 mm Hg had a Sens of 93% and a Spec of 65%, and age of younger than 43.4 years had a Sens of 14% and a Spec of 80%. Table 1 The comparison of baseline clinical, imaging and invasive haemodynamic measures between the groups Variables LMCA compression present (n = 22) LMCA compression absent (n = 247) P value Age (years) 34.6 ± 13.6 54.5 ± 16.7 <0.001 Sex (female %) 12 (54.5%) 154 (62.3%) 0.175 WHO-FC (median) 3 3 0.765 6 MWD, m (median) 286 (190–363) 268 (160–340) 0.311 PH Group (%)  Group 1 PH 19 (90.5%) 115 (48.1%) 0.003  Group 2 PH 0 13 (5.4%)  Group 3 PH 0 36 (15.1%)  Group 4 PH 2 (9.5%) 75 (31.4%) Subgroups of Group 1 PH (%)  IPAH 6 (31.6%) 51 (43.6%) 0.077  APAH-CTD 0 15 (12.8%)  APAH-CHD 13 (68.4%) 51 (43.6%) APAH-PDA (%) 8 (36.4%) 7 (2.8%) <0.001 APAH-ASD (%) 5 (23.8%) 24 (9.8%) 0.047 APAH-VSD (%) 5 (23.8%) 24 (9.8%) 0.047 Heart rate (beat per minute) 92.8 ± 16.8 87.8 ± 16.9 0.204 EF (%) 63.2 ± 3.7 61.8 ± 8.1 0.826 D-shaped septum (%) 19 (95%) 142 (64.8%) 0.023 PA diameter (mm) 46 ± 8 32 ± 7.2 <0.001 Aortic diameter (mm) 29 ± 6.7 31.2 ± 7.5 0.009 PA/aortic diameter ratio 1.62 ±0.31 1.11 ±0.25 <0.001 SBP (mmHg) 108 ± 27 124 ± 27 0.017 DBP (mmHg) 72 ± 11 72 ± 16 0.968 RA pressure (mmHg) 7.2 ± 2.3 9.5 ± 5.3 0.068 PASP (mmHg) 110 ± 24 79 ± 28 <0.001 PADP (mmHg) 49.6 ± 16 28.6 ± 15.3 <0.001 PAMP (mmHg) 72.5 ± 18.7 47.7 ± 19.3 <0.001 PVR (Wood units) 12.8 (5.9–19) 6 (4–10.8) 0.005 SVR (Wood units) 22.8 ± 7.6 22 ± 9 0.414 CO (L/min) 4.7 ± 2.2 4.6 ± 1.3 0.421 PAH targeted treatment (%)  No 3 (15.8%) 69 (29.6%) 0.287  Mono 14 (73.7%) 153 (65.7%)  Dual 2 (10.5%) 11 (4.7%) Variables LMCA compression present (n = 22) LMCA compression absent (n = 247) P value Age (years) 34.6 ± 13.6 54.5 ± 16.7 <0.001 Sex (female %) 12 (54.5%) 154 (62.3%) 0.175 WHO-FC (median) 3 3 0.765 6 MWD, m (median) 286 (190–363) 268 (160–340) 0.311 PH Group (%)  Group 1 PH 19 (90.5%) 115 (48.1%) 0.003  Group 2 PH 0 13 (5.4%)  Group 3 PH 0 36 (15.1%)  Group 4 PH 2 (9.5%) 75 (31.4%) Subgroups of Group 1 PH (%)  IPAH 6 (31.6%) 51 (43.6%) 0.077  APAH-CTD 0 15 (12.8%)  APAH-CHD 13 (68.4%) 51 (43.6%) APAH-PDA (%) 8 (36.4%) 7 (2.8%) <0.001 APAH-ASD (%) 5 (23.8%) 24 (9.8%) 0.047 APAH-VSD (%) 5 (23.8%) 24 (9.8%) 0.047 Heart rate (beat per minute) 92.8 ± 16.8 87.8 ± 16.9 0.204 EF (%) 63.2 ± 3.7 61.8 ± 8.1 0.826 D-shaped septum (%) 19 (95%) 142 (64.8%) 0.023 PA diameter (mm) 46 ± 8 32 ± 7.2 <0.001 Aortic diameter (mm) 29 ± 6.7 31.2 ± 7.5 0.009 PA/aortic diameter ratio 1.62 ±0.31 1.11 ±0.25 <0.001 SBP (mmHg) 108 ± 27 124 ± 27 0.017 DBP (mmHg) 72 ± 11 72 ± 16 0.968 RA pressure (mmHg) 7.2 ± 2.3 9.5 ± 5.3 0.068 PASP (mmHg) 110 ± 24 79 ± 28 <0.001 PADP (mmHg) 49.6 ± 16 28.6 ± 15.3 <0.001 PAMP (mmHg) 72.5 ± 18.7 47.7 ± 19.3 <0.001 PVR (Wood units) 12.8 (5.9–19) 6 (4–10.8) 0.005 SVR (Wood units) 22.8 ± 7.6 22 ± 9 0.414 CO (L/min) 4.7 ± 2.2 4.6 ± 1.3 0.421 PAH targeted treatment (%)  No 3 (15.8%) 69 (29.6%) 0.287  Mono 14 (73.7%) 153 (65.7%)  Dual 2 (10.5%) 11 (4.7%) APAH, associated pulmonary arterial hypertension; ASD, atrial septal defect; CHD, congenital heart disease; CO, cardiac output; CTD, connective tissue disease; DBP, systemic arterial diastolic blood pressure; EF %, ejection fraction%; IPAH, idiopathic pulmonary arterial hypertension; LMCA, left main coronary artery; PA, pulmonary artery; PADP, pulmonary artery diastolic pressure; PAH, pulmonary arterial hypertension; PAMP, pulmonary artery mean pressure; PASP, pulmonary artery systolic pressure; PDA, patent ductus arteriosus; PH, pulmonary hypertension; PVR, pulmonary vascular resistance; RA, right atrium; SBP, systemic arterial systolic blood pressure; SVR, systemic vascular resistance; VSD, ventricular septal defect; WHO-FC, world health organization functional class; 6MWD, six-minute walking distance. Table 1 The comparison of baseline clinical, imaging and invasive haemodynamic measures between the groups Variables LMCA compression present (n = 22) LMCA compression absent (n = 247) P value Age (years) 34.6 ± 13.6 54.5 ± 16.7 <0.001 Sex (female %) 12 (54.5%) 154 (62.3%) 0.175 WHO-FC (median) 3 3 0.765 6 MWD, m (median) 286 (190–363) 268 (160–340) 0.311 PH Group (%)  Group 1 PH 19 (90.5%) 115 (48.1%) 0.003  Group 2 PH 0 13 (5.4%)  Group 3 PH 0 36 (15.1%)  Group 4 PH 2 (9.5%) 75 (31.4%) Subgroups of Group 1 PH (%)  IPAH 6 (31.6%) 51 (43.6%) 0.077  APAH-CTD 0 15 (12.8%)  APAH-CHD 13 (68.4%) 51 (43.6%) APAH-PDA (%) 8 (36.4%) 7 (2.8%) <0.001 APAH-ASD (%) 5 (23.8%) 24 (9.8%) 0.047 APAH-VSD (%) 5 (23.8%) 24 (9.8%) 0.047 Heart rate (beat per minute) 92.8 ± 16.8 87.8 ± 16.9 0.204 EF (%) 63.2 ± 3.7 61.8 ± 8.1 0.826 D-shaped septum (%) 19 (95%) 142 (64.8%) 0.023 PA diameter (mm) 46 ± 8 32 ± 7.2 <0.001 Aortic diameter (mm) 29 ± 6.7 31.2 ± 7.5 0.009 PA/aortic diameter ratio 1.62 ±0.31 1.11 ±0.25 <0.001 SBP (mmHg) 108 ± 27 124 ± 27 0.017 DBP (mmHg) 72 ± 11 72 ± 16 0.968 RA pressure (mmHg) 7.2 ± 2.3 9.5 ± 5.3 0.068 PASP (mmHg) 110 ± 24 79 ± 28 <0.001 PADP (mmHg) 49.6 ± 16 28.6 ± 15.3 <0.001 PAMP (mmHg) 72.5 ± 18.7 47.7 ± 19.3 <0.001 PVR (Wood units) 12.8 (5.9–19) 6 (4–10.8) 0.005 SVR (Wood units) 22.8 ± 7.6 22 ± 9 0.414 CO (L/min) 4.7 ± 2.2 4.6 ± 1.3 0.421 PAH targeted treatment (%)  No 3 (15.8%) 69 (29.6%) 0.287  Mono 14 (73.7%) 153 (65.7%)  Dual 2 (10.5%) 11 (4.7%) Variables LMCA compression present (n = 22) LMCA compression absent (n = 247) P value Age (years) 34.6 ± 13.6 54.5 ± 16.7 <0.001 Sex (female %) 12 (54.5%) 154 (62.3%) 0.175 WHO-FC (median) 3 3 0.765 6 MWD, m (median) 286 (190–363) 268 (160–340) 0.311 PH Group (%)  Group 1 PH 19 (90.5%) 115 (48.1%) 0.003  Group 2 PH 0 13 (5.4%)  Group 3 PH 0 36 (15.1%)  Group 4 PH 2 (9.5%) 75 (31.4%) Subgroups of Group 1 PH (%)  IPAH 6 (31.6%) 51 (43.6%) 0.077  APAH-CTD 0 15 (12.8%)  APAH-CHD 13 (68.4%) 51 (43.6%) APAH-PDA (%) 8 (36.4%) 7 (2.8%) <0.001 APAH-ASD (%) 5 (23.8%) 24 (9.8%) 0.047 APAH-VSD (%) 5 (23.8%) 24 (9.8%) 0.047 Heart rate (beat per minute) 92.8 ± 16.8 87.8 ± 16.9 0.204 EF (%) 63.2 ± 3.7 61.8 ± 8.1 0.826 D-shaped septum (%) 19 (95%) 142 (64.8%) 0.023 PA diameter (mm) 46 ± 8 32 ± 7.2 <0.001 Aortic diameter (mm) 29 ± 6.7 31.2 ± 7.5 0.009 PA/aortic diameter ratio 1.62 ±0.31 1.11 ±0.25 <0.001 SBP (mmHg) 108 ± 27 124 ± 27 0.017 DBP (mmHg) 72 ± 11 72 ± 16 0.968 RA pressure (mmHg) 7.2 ± 2.3 9.5 ± 5.3 0.068 PASP (mmHg) 110 ± 24 79 ± 28 <0.001 PADP (mmHg) 49.6 ± 16 28.6 ± 15.3 <0.001 PAMP (mmHg) 72.5 ± 18.7 47.7 ± 19.3 <0.001 PVR (Wood units) 12.8 (5.9–19) 6 (4–10.8) 0.005 SVR (Wood units) 22.8 ± 7.6 22 ± 9 0.414 CO (L/min) 4.7 ± 2.2 4.6 ± 1.3 0.421 PAH targeted treatment (%)  No 3 (15.8%) 69 (29.6%) 0.287  Mono 14 (73.7%) 153 (65.7%)  Dual 2 (10.5%) 11 (4.7%) APAH, associated pulmonary arterial hypertension; ASD, atrial septal defect; CHD, congenital heart disease; CO, cardiac output; CTD, connective tissue disease; DBP, systemic arterial diastolic blood pressure; EF %, ejection fraction%; IPAH, idiopathic pulmonary arterial hypertension; LMCA, left main coronary artery; PA, pulmonary artery; PADP, pulmonary artery diastolic pressure; PAH, pulmonary arterial hypertension; PAMP, pulmonary artery mean pressure; PASP, pulmonary artery systolic pressure; PDA, patent ductus arteriosus; PH, pulmonary hypertension; PVR, pulmonary vascular resistance; RA, right atrium; SBP, systemic arterial systolic blood pressure; SVR, systemic vascular resistance; VSD, ventricular septal defect; WHO-FC, world health organization functional class; 6MWD, six-minute walking distance. Table 2 ROC curves, sensitivity, and specificity of the measures for prediction of LMCA compression Measures (cut-off values) AUC 95% CI Sensitivity Specificity P-value PA diameter (>40.5 mm) 0.842 0.751–0.934 92 82 <0.001 Aortic diameter (<35 mm) 0.275 0.116–0.435 14 75 0.006 PA/Aortic diameter ratio (>1.24) 0.916 0.854–0.978 91 74 <0.001 PVR (>8.8 Wood unit) 0.704 0.544–0.864 71 68 0.013 PASP (>76.5 mm Hg) 0.820 0.710–0.929 78 56 <0.001 PAMP (>49.5 mm Hg) 0.841 0.744–0.942 93 65 <0.001 PADP (>36.5 mm Hg) 0.843 0.750–0.933 78 82 <0.001 Age (<43, 4 years) 0.151 0.041–0.262 14 80 <0.001 Measures (cut-off values) AUC 95% CI Sensitivity Specificity P-value PA diameter (>40.5 mm) 0.842 0.751–0.934 92 82 <0.001 Aortic diameter (<35 mm) 0.275 0.116–0.435 14 75 0.006 PA/Aortic diameter ratio (>1.24) 0.916 0.854–0.978 91 74 <0.001 PVR (>8.8 Wood unit) 0.704 0.544–0.864 71 68 0.013 PASP (>76.5 mm Hg) 0.820 0.710–0.929 78 56 <0.001 PAMP (>49.5 mm Hg) 0.841 0.744–0.942 93 65 <0.001 PADP (>36.5 mm Hg) 0.843 0.750–0.933 78 82 <0.001 Age (<43, 4 years) 0.151 0.041–0.262 14 80 <0.001 AUC, area under curve; CI, confidence interval; LMCA, left main coronary artery; PA, pulmonary artery; PADP, pulmonary artery diastolic pressure; PAMP, pulmonary artery mean pressure; PASP, pulmonary artery systolic pressure; PVR, pulmonary vascular resistance. Table 2 ROC curves, sensitivity, and specificity of the measures for prediction of LMCA compression Measures (cut-off values) AUC 95% CI Sensitivity Specificity P-value PA diameter (>40.5 mm) 0.842 0.751–0.934 92 82 <0.001 Aortic diameter (<35 mm) 0.275 0.116–0.435 14 75 0.006 PA/Aortic diameter ratio (>1.24) 0.916 0.854–0.978 91 74 <0.001 PVR (>8.8 Wood unit) 0.704 0.544–0.864 71 68 0.013 PASP (>76.5 mm Hg) 0.820 0.710–0.929 78 56 <0.001 PAMP (>49.5 mm Hg) 0.841 0.744–0.942 93 65 <0.001 PADP (>36.5 mm Hg) 0.843 0.750–0.933 78 82 <0.001 Age (<43, 4 years) 0.151 0.041–0.262 14 80 <0.001 Measures (cut-off values) AUC 95% CI Sensitivity Specificity P-value PA diameter (>40.5 mm) 0.842 0.751–0.934 92 82 <0.001 Aortic diameter (<35 mm) 0.275 0.116–0.435 14 75 0.006 PA/Aortic diameter ratio (>1.24) 0.916 0.854–0.978 91 74 <0.001 PVR (>8.8 Wood unit) 0.704 0.544–0.864 71 68 0.013 PASP (>76.5 mm Hg) 0.820 0.710–0.929 78 56 <0.001 PAMP (>49.5 mm Hg) 0.841 0.744–0.942 93 65 <0.001 PADP (>36.5 mm Hg) 0.843 0.750–0.933 78 82 <0.001 Age (<43, 4 years) 0.151 0.041–0.262 14 80 <0.001 AUC, area under curve; CI, confidence interval; LMCA, left main coronary artery; PA, pulmonary artery; PADP, pulmonary artery diastolic pressure; PAMP, pulmonary artery mean pressure; PASP, pulmonary artery systolic pressure; PVR, pulmonary vascular resistance. Figure 3 View largeDownload slide Receiver-operating characteristics (ROC) curves of variables for prediction of LMCA compression. AO, aortae; PAPM, pulmonary arterial mean pressure. Figure 3 View largeDownload slide Receiver-operating characteristics (ROC) curves of variables for prediction of LMCA compression. AO, aortae; PAPM, pulmonary arterial mean pressure. Management of LMCA compression In patients with LMCA-Co >70% as assessed by diameter stenosis, bare-metal stents were implanted in 12 symptomatic patients (54.5%) without complication (Figure 4A–C). The median diameter and length of bare-metal stents were 4.2 mm (3.5–5.0), and 12.5 mm,9–20 respectively. One patient underwent reconstructive PA surgery and ASD repair because of mild PAH and a low PVR. Another patient declined the LMCA stenting procedure. Figure 4 View largeDownload slide (A) Left anterior oblique (LAO) cranial view of severe LMCA stenosis before stent implantation. (B) The LAO cranial view showing widening the LMCA take-off angle during full expansion of stent. (C) The LAO cranial view of LMCA immediately after stent implantation. Please note the widened angle of LMCA take-off with disappearance of ostial stenosis. Figure 4 View largeDownload slide (A) Left anterior oblique (LAO) cranial view of severe LMCA stenosis before stent implantation. (B) The LAO cranial view showing widening the LMCA take-off angle during full expansion of stent. (C) The LAO cranial view of LMCA immediately after stent implantation. Please note the widened angle of LMCA take-off with disappearance of ostial stenosis. In-hospital and post-discharge clinical course A non-sudden cardiac death was observed on 10th day of LMCA stenting in one patient with severely compromised cardiac haemodynamics prior to stenting which remains unresponsive to subsequent treatments. During regular post-discharge follow-up period of median 17.3 months no death was documented. Discussion In this single-centre study based on large series of patients with PH, LMCA-Co ≥ 50% was documented in 8.2% patients who underwent CA, and % diameter stenosis ranged between 70% and 90% in the majority of these patients. Hoarseness due to recurrent nerve compression and angina were noted in all patients with LMCA-Co. A younger age, a D-shaped septum, a higher PA systolic, mean and diastolic, pressures and PVR, a larger PA diameter with a smaller aortic diameter and clinical diagnosis of APAH-CHD due to PDA, ASD or VSD were significantly associated with LMCA-Co. The APAH due to PDA was the most powerful risk factor of LMCA-Co followed by a younger age, an increasing PA mean pressure, PA diameter, and PVR as the correlates of LMCA-Co. Bare-metal stents were implanted in 54.5% of these patients, and one patient underwent reconstructive PA surgery with ASD repair. Proximal LMCA-Co by a PAA was first described as a complication of severe PH 60 years ago.3 Moreover, other situations resulting in PAA have also been documented to cause LMCA-Co.3–17 The majority of the data concerning LMCA stenting in this setting have been based on case reports or small series.7,8,13–17 Cardiac MDCT provides a comprehensive method to evaluate the severity of extrinsic LMCA-Co, the angulation of this vessel relative to the left sinus of Valsalva, the underlying pathology of PAA, and left and right ventricular functions.7,9,13–17 The degree of compression, a LMCA angle of take-off from the left sinus of Valsalva of <30% and a main PA/aorta diameter ratio >2.0 have been reported to increase the risk for LMCA-Co.7–17 In the ever largest series of Galie et al.16 in which LMCA deformation patterns and management strategies were evaluated, 121 out of the 765 (15.8%) patients with PAH underwent MDCT because of their angina or angina-like symptoms. Four MDCT patterns described were as follows; (i) LMCA-Co, (ii) LMCA dislocation (a take-off angle <60° without compression), (iii) close proximity (PA to LMCA distance <1 mm, and (iv) normal pattern (PA to LMCA distance >1 mm). The MDCT evaluation showed LMCA–Co, LMCA dislocation and close proximity patterns in 28.9%, 40.5% and 8.3% of the patients, respectively.16 Patients with first three patterns underwent selective CA, and LMCA–Co ≥ 50% was diagnosed in 39, 7% of those with angina or angina-like chest pain. In other words, LMCA-Co was documented in 6% of the overall PH patients. Main PA diameter >40 mm as assessed by MDCT was found to predict LMCA-Co ≥ 50%, and angiographic LMCA-Co ≥ 50% was diagnosed in 10%, 30, 6%, and 91, 4% of the proximity, dislocation and compression patterns of MDCT, respectively.16 The LMCA-Co ≥ 50% was noted in 8.2% of our patients who underwent CA, and 4.4% of overall PH patients. The LMCA-Co has been reported to be associated with PA diameter and PA diameter/aortic diameter ratio, but not with the severity of PAH in two large PAH series.13,16 In contrast to these series, we found that not only PA diameter and PA diameter/aortic diameter ratio, but also clinical etiology of PDA, a younger age, and severity of PAH as defined by higher PA mean pressure and PVR predicted the risk of LMCA-Co. We also found that LMCA take-off angle in reference to left sinus of Valsalva was lower than 30° in all patients with LMCA-Co. However, neither the optimal treatment of PAA, nor management of LMCA-Co have been standardized. Because of the risk of PAA dissection and rupture, an aggressive surgical approach has been advocated for patients with PH.18–24,27–30 Although there is no evidence-based consensus for surgery, adults with main PAA diameter >5.5 cm, ≥5 mm increase in the diameter of the PAA in 6 months, clinical symptoms, co-existing severe valvular pathologies or shunt flow, and verification of extrinsic compression of LMCA or adjacent structures, thrombus formation in the PAA are considered as indications for surgery.18–30 On the other hand, patients with PH may have a high surgical risk and may need a heart-lung transplantation.18–28 The LMCA stenting with encouraging angiographic results and satisfactory short-term clinical outcomes has been developed as the revascularization strategy of choice, and compression of the ostial or proximal part of this artery, sparing the LMCA bifurcation permits a single stent placement.7–17 In the large series of Galie et al.16 85.4% of patients with LMCA stenosis >50% underwent LMCA stenting whereas both the rate of LMCA-Co and the LMCA stenting were lower in our study group. Moreover, in contrast to 48.9% rate of drug eluting stent placement in the series of Galie et al.,16 only bare metal stents were used for LMCA-Co treatment in our study. Because of the large diameters of LMCA, benefit of drug eluting stents in this setting has remained unproven whereas durability of radial force against extrinsic compression is a major challenge.16,17 Long-term follow-up data of these patients after LMCA stenting suggest a favourable clinical outcome despite the presence of a trend for statistically significant re-narrowing of the LMCA after stenting.16 This implies the ongoing risk for progressive compression of LMCA by enlarged and overloaded PAs.16,17 Galie et al.16 reported that the rates for death or double-lung transplant and rates for death, double-lung transplant, or restenosis of patients undergoing stenting or PA surgical plasty for LMCA-Co were 5% and 30% at 3 years, respectively. Except one in-hospital death seeming to be associated with underlying heart failure, we documented no death during follow-up of period. The selection of best methods for adjunctive periprocedural imaging and physiologic assessment in this patients is another concern.17,31 Intravascular ultrasound with or without pressure wire can also be used as a guidance method to evaluate the LMCA-Co and to assess optimal stent sizing, deployment and apposition during stenting.31 Because of the ostial location of the LMCA segment to be stented, the risk of stent displacement to the aorta is another critical issue.32 Moreover, long-term antiplatelet management after LMCA stenting is another controversy in these patients. Limitations The absence of the detailed MDCT morphologic definition which may be predictive for LMCA-Co patterns, and quantitative assessment of flow obliteration in the presence of ovoid-shaped lumen with currently available methods such as intravascular ultrasound or fractional flow reserve in the decision making for management strategy may be considered as important limitations. The durability of the radial force of bare metal stents against progressive extrinsic compression due to increasing PA pressures is another concern. The long-term prospective randomized studies seem to be needed to evaluate whether LMCA stenting provides any additive benefit beyond the targeted PH treatments in this setting. Moreover, because of the too small size of the subgroup of patients with significant LMCA-Co, the multiple linear regression analysis that could be very important to evaluate the independent roles of different determinants on the genesis this complication was not possible. Accordingly, this issue remains as an important limitation of this study, and description of the findings should be less absolute since ROC analysis per se cannot be conclusive. Conclusions We demonstrate that LMCA-Co is the one of the most important complications of severe PAH, and alertness for this risk seems to be necessary in younger patients and in specific circumstances related with PAA including PDA and haemodynamically severe pulmonary vascular diseases. However, long-term benefit from LMCA stenting in this setting remains as a controversy. Acknowledgements The authors thank www.metastata.com for their contributions to statistical analysis and trial design. Conflict of interest: None declared. References 1 Galiè N , Hoeper MM , Humbert M , Torbicki A , Vachiery JL , Barbera JA ; ESC Committee for Practice Guidelines (CPG) . 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Journal

European Heart Journal – Cardiovascular ImagingOxford University Press

Published: Dec 8, 2017

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