Prevalence and Outcomes of Percutaneous Coronary Interventions for Ostial Chronic Total Occlusions: Insights From a Multicenter Chronic Total Occlusion Registry

Ostial chronic total occlusions (CTOs) can be challenging to recanalize.We sought to examine the prevalence, angiographic presentation, and procedural outcomes of ostial (side-branch ostial and aorto-ostial) CTOs among 1000 CTO percutaneous coronary interventions (PCIs) performed in 971 patients between 2015 and 2017 at 14 centres in the US, Europe, and Russia.Ostial CTOs represented 16.9% of all CTO PCIs: 9.6% were aorto-ostial, and 7.3% were side-branch ostial occlusions. Compared with nonostial CTOs, ostial CTOs were longer (44 ± 33 vs 29 ± 19 mm, P < 0.001) and more likely to have proximal-cap ambiguity (55% vs 33%, P < 0.001), moderate/severe calcification (67% vs 45%, P < 0.001), a diffusely diseased distal vessel (41% vs 26%, P < 0.001), interventional collaterals (64% vs 53%, P = 0.012), and previous coronary artery bypass graft surgery (CABG) (51% vs 27%, P < 0.001). The retrograde approach was used more often in ostial CTOs (54% vs 29%, P < 0.001) and was more often the final successful crossing strategy (30% vs 18%, P = 0.003). Technical (81% vs 84%, P = 0.280), and procedural (77% vs 83%, P = 0.112) success rates and the incidence of in-hospital major complication were similar (4.8% vs 2.2%, P = 0.108), yet in-hospital mortality (3.0% vs 0.5%, P = 0.010) and stroke (1.2% vs 0.0%, P = 0.030) were higher in the ostial CTO PCI group. In multivariable analysis, ostial CTO location was not independently associated with higher risk for in-hospital major complications (adjusted odds ratio 1.27, 95% confidence intervals 0.37 to 4.51, P = 0.694).Ostial CTOs can be recanalized with similar rates of success as nonostial CTOs but are more complex, more likely to require retrograde crossing and may be associated with numerically higher risk for major in-hospital complications

In-hospital Outcomes of Attempting More Than One Chronic Total Coronary Occlusion Through Percutaneous Intervention During the Same Procedure

The frequency and outcomes of patients who underwent chronic total occlusion (CTO) percutaneous coronary intervention (PCI) of more than one CTO during the same procedure have received limited study. We compared the clinical and angiographic characteristics and procedural outcomes of patients who underwent treatment of single versus >1 CTOs during the same procedure in 20 centers from the United States, Europe, and Russia. A total of 2,955 patients were included: mean age was 65 ± 10 years and 85% were men with high prevalence of previous myocardial infarction (46%), and previous coronary artery bypass graft surgery (33%). More than one CTO lesions were attempted during the same procedure in 58 patients (2.0%) and 70% of them were located in different major epicardial arteries. Compared with patients who underwent PCI of a single CTO, those who underwent PCI of >1 CTOs during the same procedure had similar J-CTO (2.4 ± 1.3 vs 2.5 ± 1.3, p = 0.579) and Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (1.5 ± 1.2 vs 1.3 ± 1.0 p = 0.147) scores. The multi-CTO PCI group had similar technical success (86% vs 87%, p = 0.633), but higher risk of in-hospital major complications (10.3% vs 2.7%, p = 0.005), and consequently numerically lower procedural success (79% vs 85%, p = 0.197). The multi-CTO PCI group had higher in-hospital mortality (5.2% vs 0.5%, p = 0.005) and stroke (5.2%vs 0.2%, p 1 CTO lesions requiring revascularization, as treatment during a single procedure was associated with higher risk for periprocedural complications

Use of Intravascular Imaging During Chronic Total Occlusion Percutaneous Coronary Intervention: Insights From a Contemporary Multicenter Registry

Background: Intravascular imaging can facilitate chronic total occlusion (CTO) percutaneous coronary intervention. Methods and Results: We examined the frequency of use and outcomes of intravascular imaging among 619 CTO percutaneous coronary interventions performed between 2012 and 2015 at 7 US centers. Mean age was 65.4±10 years and 85% of the patients were men. Intravascular imaging was used in 38%: intravascular ultrasound in 36%, optical coherence tomography in 3%, and both in 1.45%. Intravascular imaging was used for stent sizing (26.3%), stent optimization (38.0%), and CTO crossing (35.7%, antegrade in 27.9%, and retrograde in 7.8%). Intravascular imaging to facilitate crossing was used more frequently in lesions with proximal cap ambiguity (49% versus 26%, P<0.0001) and with retrograde as compared with antegrade‐only cases (67% versus 31%, P<0.0001). Despite higher complexity (Japanese CTO score: 2.86±1.19 versus 2.43±1.19, P=0.001), cases in which imaging was used for crossing had similar technical and procedural success (92.8% versus 89.6%, P=0.302 and 90.1% versus 88.3%, P=0.588, respectively) and similar incidence of major cardiac adverse events (2.7% versus 3.2%, P=0.772). Use of intravascular imaging was associated with longer procedure (192 minutes [interquartile range 130, 255] versus 131 minutes [90, 192], P<0.0001) and fluoroscopy (71 minutes [44, 93] versus 39 minutes [25, 69], P<0.0001) time. Conclusions: Intravascular imaging is frequently performed during CTO percutaneous coronary intervention both for crossing and for stent selection/optimization. Despite its use in more complex lesion subsets, intravascular imaging was associated with similar rates of technical and procedural success for CTO percutaneous coronary intervention. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02061436

New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics

Primary open-angle glaucoma (POAG), the most common optic neuropathy, is a highly heritable disease (h2 = 0.42 ± 0.09). Siblings of POAG cases have a ten-fold increase risk of developing the disease. Intraocular pressure (IOP) and optic nerve head characteristics are used clinically to predict POAG risk. We conducted a genome-wide association meta-analysis of IOP and optic disc parameters and validated our findings in multiple sets of POAG cases and controls. Using imputation to the 1000 genomes (1000G) reference set, we identified 9 new genomic regions associated with vertical cup disc ratio (VCDR) and 1 new region associated with IOP. Additionally, we found 5 novel loci for optic nerve cup area and 6 for disc area. Previously it was assumed that genetic variation influenced POAG either through IOP or via changes to the optic nerve head; here we present evidence that some genomic regions affect both IOP and the disc parameters. We characterized the effect of the novel loci through pathway analysis and found that pathways involved are not entirely distinct as assumed. Further, we identified a novel association between CDKN1A and POAG. Using a zebrafish model we show that six6b (associated with POAG and optic nerve head variation) alters the expression of cdkn1a. In summary, we have identified several novel genes influencing the major clinical risk predictors of POAG and showed that genetic variation in CDKN1A is important in POAG ris

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries

The Impact of Proximal Vessel Tortuosity on the Outcomes of Chronic Total Occlusion Percutaneous Coronary Intervention: Insights From a Contemporary Multicenter Registry

Introduction. We examined the impact of proximal vessel tortuosity on the outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI). Methods. The baseline clinical and angiographic characteristics and procedural outcomes of 1618 consecutive CTO-PCIs performed between 2012 and 2016 at 14 United States centers in 1589 patients were reviewed. Results. Mean patient age was 65.3 +/- 10.0 years and 85% were men. Moderate/severe proximal vessel tortuosity was present in 35.7% of target lesions. Compared with non-tortuous lesions, tortuous lesions had longer length (30 mm [interquartile range, 2050 mm] vs 28 mm [ interquartile range, 16-40 mm]; P<.001), more proximal cap ambiguity (36% vs 28%; P<.01), and more frequent utilization of the retrograde approach (52% vs 37%; P<.001). Moderate/severe proximal vessel tortuosity was associated with lower technical success rates (84.1% vs 91.3%; P<.001) and procedural success rates (82.3% vs 89.9%; P<.001), but similar incidence of major cardiac adverse events (3.0% vs 2.5%; P=.59). Moderate/severe tortuosity was associated with longer procedure time and fluoroscopy time, higher air kerma radiation dose, and larger contrast volume. Conclusion. In a contemporary multicenter registry, moderate/severe proximal vessel tortuosity was present in approximately one-third of target CTO lesions and was associated with more frequent use of the retrograde approach and lower success rates, but similar complication rates

Retrograde CTO-PCI of Native Coronary Arteries Via Left Internal Mammary Artery Grafts: Insights From a Multicenter US Registry

Background. Retrograde percutaneous coronary intervention (PCI) of native coronary artery chronic total occlusion (CTO) via left internal mammary artery (LIMA) graft has received limited study. Methods and Results. We compared the clinical and procedural characteristics and outcomes of retrograde CTO-PCI through LIMA grafts vs other conduits in a contemporary multicenter CTO registry. The LIMA was used as the collateral channel in 20 of 990 retrograde CTO-PCIs (2.02%) performed at 18 United States centers. The mean age of the study patients was 69 +/- 7 years and 95% were men. The most common CTO target vessel was the right coronary artery (55%). The mean J-CTO score in the LIMA group was high (3.45 +/- 0.76). The technical success rates were 70% for retrograde PCI via LIMA graft vs 81.05% for retrograde via other conduits (P=.25). while procedural success rates were 70% for retrograde PCI via LIMA graft and 78.19% for retrograde via other conduits (P=.41). The incidence of major in-hospital complications was also similar between the LIMA and non-LIMA retrograde groups (5% vs 6%; P>.99). Use of guide-catheter extensions (40% vs 28%; P=.22), intravascular ultrasound (45% vs 31%; P=.20), and left ventricular assist devices (24% vs 10%; P=.08) was numerically higher in retrograde CTO-PCIs via LIMA grafts. Conclusions. Retrograde CTO-PCI is infrequently performed via LIMA grafts and is associated with similar success and major in-hospital complication rates as retrograde CTO-PCI performed via other conduits

Prevalence, Presentation and Treatment of 'Balloon Undilatable' Chronic Total Occlusions: Insights from a Multicenter US Registry

BACKGROUND: The prevalence, treatment and outcomes of balloon undilatable chronic total occlusions (CTOs) have received limited study. METHODS: We examined the prevalence, clinical and angiographic characteristics, and procedural outcomes of percutaneous coronary interventions (PCIs) for balloon undilatable CTOs in a contemporary multicenter US registry. RESULTS: Between 2012 and 2017 data on balloon undilatable lesions were available for 425 consecutive CTO PCIs in 415 patients in whom guidewire crossing was successful: 52 of 425 CTOs were balloon undilatable (12%). Mean patient age was 65 +/- 10 years and most patients were men (84%). Patients with balloon undilatable CTOs were more likely to be diabetic (67 vs. 41%, P < 0.001) and have heart failure (44 vs. 28%, P = 0.027). Balloon undilatable CTOs were longer (40 mm [interquartile range, IQR 20-50] vs. 30 [IQR 15-40], P = 0.016), more likely to have moderate/severe calcification (87 vs. 54%, P < 0.001), and had higher J-CTO score (3.2 +/- 1.1 vs. 2.5 +/- 1.3, P < 0.001) and PROGRESS-CTO complications score (3.9 +/- 1.7 vs. 3.1 +/- 2.0, P < 0.005). They were associated with lower technical and procedural success (92 vs. 98%, P = 0.024; and 88 vs. 96%, P = 0.034, respectively) and higher risk for in-hospital major adverse events (8 vs. 2%, P = 0.008) due to higher perforation rates. The most frequent treatments for balloon undilatable CTOs were high pressure balloon inflations (64%), rotational atherectomy (31%), laser (21%), and cutting balloons (15%). CONCLUSIONS: Balloon undilatable CTOs are common and are associated with lower success and higher complication rates. CLINICAL TRIAL REGISTRATION: NCT02061436, Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (PROGRESS CTO)