Distal Radial Access in Chronic Total Occlusion Percutaneous Coronary Intervention: Insights From the PROGRESS-CTO Registry.

BACKGROUND: The outcomes of distal radial access (dRA) in chronic total occlusion percutaneous coronary intervention (CTO-PCI) have received limited study. METHODS: We compared the clinical, angiographic, and procedural characteristics of 120 CTO-PCIs performed via dRA access with 2625 CTO-PCIs performed via proximal radial access (pRA) in a large, multicenter registry. RESULTS: The dRA group had lower mean PROGRESS-CTO score than the pRA group (1.0 ± 1 vs 1.2 ± 1, respectively; P=.05), while J-CTO score (2.4 ± 1.2 vs 2.3 ± 1.3; P=.43) and PROGRESS-CTO Complications score (2.8 ± 1.8 vs 2.6 ± 1.9; P=.16) were similar in the dRA vs pRA groups, respectively. Technical success was similar in the 2 groups (90% dRA vs 86% pRA; P=.14). Concomitant use of femoral access did not alter procedural success. The incidence of major periprocedural adverse cardiac events was similar in the 2 groups (0.8% dRA vs 2.4% pRA; P=.26), whereas the incidence of tamponade requiring pericardiocentesis was lower with dRA (0% dRA vs 4.69% pRA; P<.001), as was air kerma radiation dose (median, 1.7 Gy; interquartile range [IQR], 0.97-2.63 Gy in the dRA group vs median, 2.27 Gy; IQR, 1.2-3.9 Gy in the pRA group; P<.001). CONCLUSIONS: Use of dRA in CTO-PCI is associated with similar procedural success and risk of complications as compared with pRA.

Follow-up Outcomes After Chronic Total Occlusion Percutaneous Coronary Intervention in Patients With and Without Prior Coronary Artery Bypass Graft Surgery: Insights From the PROGRESS-CTO Registry.

BACKGROUND: Long-term outcomes of patients with prior coronary artery bypass graft (CABG) surgery undergoing chronic total occlusion (CTO) percutaneous coronary intervention (PCI) have received limited study. METHODS: We compared the clinical and angiographic characteristics and procedural and follow-up outcomes of patients with and without prior CABG in a multicenter international registry. RESULTS: Of the 1572 patients included in this analysis, a total of 498 (32%) had prior CABG. Prior CABG patients had higher J-CTO scores (2.9 ± 1.1 vs 2.2 ± 1.3; P<.001) and were less likely to undergo PCI of the left anterior descending artery (16.7% vs 29.6%; P<.001). The retrograde technique was used more often (47.4% vs 28.2%; P<.001) and was successful more often (27.4% vs 17.1%; P<.001) in the prior CABG group vs the non-prior CABG group. Technical success was lower in prior CABG patients (82.6% vs 87.9%; P<.01) with similar incidence of in-hospital major adverse cardiovascular events (3.4% vs 3%; P=.65), although in-hospital mortality was higher in the prior CABG group (2.4% vs 1.0%; P=.04). At 1-year follow-up, the composite endpoint of death, myocardial infarction, and revascularization was higher in prior CABG patients (21.79% vs 12.73%; hazard ratio, 1.76; 95% confidence interval, 1.27-2.45; P<.001). CONCLUSION: Compared with non-prior CABG patients, prior CABG patients undergoing CTO-PCI had lower technical success and higher incidence of acute and follow-up adverse cardiovascular events.

Retrograde Chronic Total Occlusion Percutaneous Coronary Intervention via Saphenous Vein Graft.

OBJECTIVES: The aim of this study was to examine the use of saphenous vein grafts (SVGs) for retrograde crossing during chronic total occlusion (CTO) percutaneous coronary intervention (PCI). BACKGROUND: The use of SVGs for retrograde crossing during CTO PCI has received limited study. METHODS: A total of 1,615 retrograde CTO PCIs performed between 2012 and 2019 at 25 centers were examined. Clinical, angiographic, and technical characteristics and procedural outcomes were compared among retrograde cases via SVGs (SVG group) versus other collateral vessels (non-SVG group). RESULTS: Retrograde CTO PCI via SVGs was performed in 189 cases (12%). Patients in the SVG group were older (mean age 70 ± 9 years vs. 64 ± 10 years; p < 0.01) and had higher rates of prior myocardial infarction (62% vs. 51%; p < 0.01) and prior PCI (81% vs. 70%; p < 0.01). They were more likely to have moderate or severe calcification (81% vs. 65%; p < 0.01) and moderate or severe tortuosity (53% vs. 44%; p = 0.02) and had similar J-CTO (Multicenter CTO Registry in Japan) scores (3.2 ± 1.0 vs. 3.1 ± 1.1; p = 0.13) but higher PROGRESS-CTO (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention) scores (4.7 ± 1.7 vs. 3.1 ± 1.1; p < 0.01). Technical (85% vs. 78%; p = 0.04) and procedural (81% vs. 74%; p = 0.04) success rates were higher in the SVG group, with no difference in in-hospital major adverse events (6.4% vs. 4.4%; p = 0.22). Contrast volume was lower in the SVG group (225 ml [173 to 325 ml] vs. 292 ml [202 to 400 ml]; p < 0.01). CONCLUSIONS: Use of SVGs for retrograde crossing is associated with higher rates of technical and procedural success and similar rates of in-hospital major adverse cardiac events compared with retrograde CTO PCI via other collateral vessels.

Left Main Chronic Total Occlusion Percutaneous Coronary Intervention: A Case Series.

BACKGROUND: Left main coronary artery (LMCA) chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study. METHODS: We reviewed 4436 CTO-PCIs performed in 4340 patients between 2012 and 2018 at 25 sites. LMCA-CTO-PCI was performed in 20 cases (0.45%). We examined the clinical and angiographic characteristics and procedural outcomes of these cases. RESULTS: Mean patient age was 68 ± 11 years and 65% were men. Most patients (85%) had undergone prior coronary artery bypass graft surgery and had a protected left main. Mean J-CTO score was 2.7 ± 1.3, mean PROGRESS-CTO score was 1.3 ± 1.1, and mean PROGRESS-CTO Complications score was 3.8 ± 1.9. Antegrade-wire escalation was the most common successful crossing strategy (50%), followed by retrograde crossing (30%) and antegrade dissection/re-entry (10%). Technical and procedural success rates were both 85%. One patient with failed LMCA-CTO-PCI had periprocedural myocardial infarction. Median procedure time was 178 minutes (interquartile range [IQR], 123-250 minutes), median contrast volume was 190 mL (IQR, 133-339 mL), and patient air kerma radiation dose was 2.6 Gray (IQR, 1.3-3.9 Gray). CONCLUSIONS: LMCA-CTO-PCI is infrequent, is performed mostly in patients with prior coronary artery bypass graft surgery, and is associated with good procedural outcomes.

Contemporary Use and Trends in Unprotected Left Main Coronary Artery Percutaneous Coronary Intervention in the United States: An Analysis of the National Cardiovascular Data Registry Research to Practice Initiative.

Importance: Recent data support percutaneous revascularization as an alternative to coronary artery bypass grafting in unprotected left main (ULM) coronary lesions. However, the relevance of these trials to current practice is unclear, as patterns and outcomes of ULM percutaneous coronary intervention (PCI) in contemporary US clinical practice are not well studied. Objective: To define the current practice of ULM PCI and its outcomes and compare these with findings reported in clinical trials. Design, Setting, and Participants: This cross-sectional multicenter analysis included data collected from 1662 institutions participating in the National Cardiovascular Data Registry (NCDR) CathPCI Registry between April 2009 and July 2016. Data were collected from 33 128 patients undergoing ULM PCI and 3 309 034 patients undergoing all other PCI. Data were analyzed from June 2017 to May 2018. Main Outcomes and Measures: Patient and procedural characteristics and their temporal trends were compared between ULM PCI and all other PCI. In-hospital major adverse clinical events (ie, death, myocardial infarction, stroke, and emergent coronary artery bypass grafting) were compared using hierarchical logistic regression. Characteristics and outcomes were also compared against clinical trial cohorts. Results: Of the 3 342 162 included patients, 2 223 570 (66.5%) were male, and the mean (SD) age was 64.2 (12.1) years. Unprotected left main PCI represented 1.0% (33 128 of 3 342 162) of all procedures, modestly increasing from 0.7% to 1.3% over time. The mean (SD) annualized ULM PCI volume was 0.5 (1.5) procedures for operators and 3.2 (6.1) procedures for facilities, with only 1808 of 10 971 operators (16.5%) and 892 of 1662 facilities (53.7%) performing an average of 1 or more ULM PCI annually. After adjustment, major adverse clinical events occurred more frequently with ULM PCI compared with all other PCI (odds ratio, 1.46; 95% CI, 1.39-1.53). Compared with clinical trial populations, patients in the CathPCI Registry were older with more comorbid conditions, and adverse events were more frequent. Conclusions and Relevance: Use of ULM PCI has increased over time, but overall use remains low. These findings suggest that ULM PCI occurs infrequently in the United States and in an older and more comorbid population than that seen in clinical trials.

Cost implications of intraprocedural thrombotic events and bleeding in percutaneous coronary intervention: Results from the CHAMPION PHOENIX ECONOMICS Study.

BACKGROUND: Despite improvements in percutaneous coronary intervention (PCI), intraprocedural thrombotic events (IPTE) and bleeding complications occur and are prognostically important. These have not been included in prior economic studies. METHODS: PHOENIX ECONOMICS was a substudy of the CHAMPION PHOENIX trial, evaluating cangrelor during PCI. Hospital bills were reviewed from 1,171 patients enrolled at 22 of 63 US sites. Costs were estimated using standard methods including resource-based accounting, hospital billing data, and the Medicare fee schedule. Bleeding and IPTE, defined as abrupt vessel closure (transient or sustained), new/suspected thrombus, new clot on wire/catheter, no reflow, side-branch occlusion, procedural stent thrombosis or urgent need for CABG were identified. Costs were calculated according to whether a complication occurred and type of event. Multivariate analyses were used to estimate the incremental costs of IPTE and postprocedural events. RESULTS: IPTE occurred in 4.3% and were associated with higher catheterization laboratory and overall index hospitalization costs by $2,734 (95%CI $1,117, $4,351; P = 0.001) and $6,354 (95% CI $4,122, $8,586; P < 0.001), respectively. IPTE were associated with MI (35.4% vs. 3.6%; P < 0.001), out-of-laboratory stent thrombosis (4.2% vs. 0.1%; 0 = 0.005), ischemia driven revascularization (12.5% vs. 0.3%; P < 0.001), but not mortality (2.1% vs. 0.2%; P = 0.12) vs. no procedural thrombotic complication. By comparison, ACUITY minor bleeding increased hospitalization cost by $1,416 (95%CI = 312, $2,519; P = 0.012). ACUITY major bleeding increased cost of hospitalization by $7,894 (95%CI $4,154, $11,635; P < 0.001). CONCLUSIONS: IPTE and bleeding complications, though infrequent, are associated with substantial increased cost. These complications should be collected in economic assessments of PCI.

Effect of Short Procedural Duration With Bivalirudin on Increased Risk of Acute Stent Thrombosis in Patients With STEMI: A Secondary Analysis of the HORIZONS-AMI Randomized Clinical Trial.

Importance: Bivalirudin has been associated with reduced bleeding and mortality during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction (STEMI). However, increased rates of acute stent thrombosis (AST) have been noted when bivalirudin is discontinued at the end of the procedure, which is perhaps related to this medication's short half-life. Objectives: To evaluate the clinical effect of procedure duration on AST when either bivalirudin or heparin plus glycoprotein IIb/IIIa receptor inhibitor (GPI) is used. Design, Setting, and Participants: An ad hoc analysis of the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) clinical trial was performed between March 1, 2015, and April 30, 2016, on patients who underwent primary percutaneous coronary intervention with stents and were randomized 1:1 to bivalirudin or heparin plus GPI. Defined as the difference between the patient's arrival at the catheterization laboratory and the patient's final angiogram. Participants included 3602 patients with STEMI, aged 18 years or older, who were undergoing primary percutaneous coronary intervention and presenting less than 12 hours from symptom onset. Main Outcomes and Measures: Clinical events committee-adjudicated definite AST (occurring ≤24 hours after percutaneous coronary intervention). Results: Among patients included in this analysis, procedure time was identified in 1286 receiving bivalirudin and 1412 receiving heparin plus GPI. Shorter procedures were defined as the lowest quartile of duration (<45 minutes). Patients undergoing shorter procedures were younger and less likely to be hypertensive and smokers. Shorter procedures were less complicated with fewer stents implanted, less multivessel stenting, less thrombus, and less no-reflow. An increased risk of definite AST was associated with shorter than with longer procedures with bivalirudin (7 [2.1%] vs 7 [0.7%]; relative risk, 2.87; 95% CI, 1.01-8.17; P = .04) but not with heparin plus GPI (0 vs 3 [0.3%]; P = .30). Conclusions and Relevance: Despite less procedural complexity, shorter primary percutaneous coronary intervention time was associated with an increased risk of AST in patients treated with bivalirudin but not patients treated with heparin plus GPI, possibly because of the rapid offset of bivalirudin's antithrombotic effect during a window of limited oral antiplatelet action. Trial Registration: clinicaltrials.gov Identifier: NCT00433966.

Removal of Soluble Fms-Like Tyrosine Kinase-1 by Dextran Sulfate Apheresis in Preeclampsia.

Preeclampsia is a devastating complication of pregnancy. Soluble Fms-like tyrosine kinase-1 (sFlt-1) is an antiangiogenic protein believed to mediate the signs and symptoms of preeclampsia. We conducted an open pilot study to evaluate the safety and potential efficacy of therapeutic apheresis with a plasma-specific dextran sulfate column to remove circulating sFlt-1 in 11 pregnant women (20-38 years of age) with very preterm preeclampsia (23-32 weeks of gestation, systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, new onset protein/creatinine ratio >0.30 g/g, and sFlt-1/placental growth factor ratio >85). We evaluated the extent of sFlt-1 removal, proteinuria reduction, pregnancy continuation, and neonatal and fetal safety of apheresis after one (n=6), two (n=4), or three (n=1) apheresis treatments. Mean sFlt-1 levels were reduced by 18% (range 7%-28%) with concomitant reductions of 44% in protein/creatinine ratios. Pregnancy continued for 8 days (range 2-11) and 15 days (range 11-21) in women treated once and multiple times, respectively, compared with 3 days (range 0-14) in untreated contemporaneous preeclampsia controls (n=22). Transient maternal BP reduction during apheresis was managed by withholding pre-apheresis antihypertensive therapy, saline prehydration, and reducing blood flow through the apheresis column. Compared with infants born prematurely to untreated women with and without preeclampsia (n=22 per group), no adverse effects of apheresis were observed. In conclusion, therapeutic apheresis reduced circulating sFlt-1 and proteinuria in women with very preterm preeclampsia and appeared to prolong pregnancy without major adverse maternal or fetal consequences. A controlled trial is warranted to confirm these findings.

Carbamylation of serum albumin and erythropoietin resistance in end stage kidney disease.

BACKGROUND AND OBJECTIVES: The mechanisms underlying erythropoietin resistance are not fully understood. Carbamylation is a post-translational protein modification that can alter the function of proteins, such as erythropoietin. The hypothesis of this study is that carbamylation burden is independently associated with erythropoietin resistance. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a nonconcurrent prospective cohort study of incident hemodialysis patients in the United States, carbamylated albumin, a surrogate of overall carbamylation burden, in 158 individuals at day 90 of dialysis initiation and erythropoietin resistance index (defined as average weekly erythropoietin dose [U] per kg body weight per hemoglobin [g/dl]) over the subsequent 90 days were measured. Linear regression was used to describe the relationship between carbamylated albumin and erythropoietin resistance index. Logistic regression characterized the relationship between erythropoietin resistance index, 1-year mortality, and carbamylation. RESULTS: The median percent carbamylated albumin was 0.77% (interquartile range=0.58%-0.93%). Median erythropoietin resistance index was 18.7 units/kg per gram per deciliter (interquartile range=8.1-35.6 units/kg per gram per deciliter). Multivariable adjusted analysis showed that the highest quartile of carbamylated albumin was associated with a 72% higher erythropoietin resistance index compared with the lowest carbamylation quartile (P=0.01). Increasing erythropoietin resistance index was associated with a higher risk of death (odds ratio per unit increase in log-erythropoietin resistance index, 1.69; 95% confidence interval, 1.06 to 2.70). However, the association between erythropoietin resistance index and mortality was no longer statistically significant when carbamylation was included in the analysis (odds ratio, 1.44; 95% confidence interval, 0.87 to 2.37), with carbamylation showing the dominant association with death (odds ratio for high versus low carbamylation quartile, 4.53; 95% confidence interval, 1.20 to 17.10). CONCLUSION: Carbamylation was associated with higher erythropoietin resistance index in incident dialysis patients and a better predictor of mortality than erythropoietin resistance index.

Soluble erythropoietin receptor contributes to erythropoietin resistance in end-stage renal disease.

BACKGROUND: Erythropoietin is a growth factor commonly used to manage anemia in patients with chronic kidney disease. A significant clinical challenge is relative resistance to erythropoietin, which leads to use of successively higher erythropoietin doses, failure to achieve target hemoglobin levels, and increased risk of adverse outcomes. Erythropoietin acts through the erythropoietin receptor (EpoR) present in erythroblasts. Alternative mRNA splicing produces a soluble form of EpoR (sEpoR) found in human blood, however its role in anemia is not known. METHODS AND FINDINGS: Using archived serum samples obtained from subjects with end stage kidney disease we show that sEpoR is detectable as a 27kDa protein in the serum of dialysis patients, and that higher serum sEpoR levels correlate with increased erythropoietin requirements. Soluble EpoR inhibits erythropoietin mediated signal transducer and activator of transcription 5 (Stat5) phosphorylation in cell lines expressing EpoR. Importantly, we demonstrate that serum from patients with elevated sEpoR levels blocks this phosphorylation in ex vivo studies. Finally, we show that sEpoR is increased in the supernatant of a human erythroleukaemia cell line when stimulated by inflammatory mediators such as interleukin-6 and tumor necrosis factor alpha implying a link between inflammation and erythropoietin resistance. CONCLUSIONS: These observations suggest that sEpoR levels may contribute to erythropoietin resistance in end stage renal disease, and that sEpoR production may be mediated by pro-inflammatory cytokines.

Risk for developing gestational diabetes in women with twin pregnancies.

OBJECTIVE: To examine the risk of developing gestational diabetes mellitus (GDM) in women with twin compared with singleton pregnancies. RESEARCH DESIGN AND METHODS: We examined a cohort of 23,056 pregnant women who gave birth to a live infant between 1 September 1998 and 31 December 2006, 553 of whom had twin pregnancy. The primary exposure was twin versus singleton pregnancy, and the primary outcome was the development of GDM. Standard univariate analyses were performed, as were multivariable analysis with logistic regression to control for potential confounding variables. GDM was diagnosed using criteria of the National Diabetes Data Group. RESULTS: Patients with twin pregnancies had a higher rate of GDM when compared with singleton pregnancies (3.98% vs. 2.32%; p = 0.01). In a multiple regression analysis after adjusting for age, race/ethnicity, body mass index, maximal systolic and diastolic blood pressure, smoking and parity, twin pregnancy was associated with an approximately two-fold increase in risk for developing GDM (OR 2.2, 95% CI 1.4-3.6). In a stratified analysis, women between the ages of 25 and 30 years and African-American women had the highest risk of developing GDM in twin pregnancies. When compared with twins of non-diabetic mothers, twins of gestational diabetics had a higher rate of admission to the neonatal intensive care unit (37%vs. 52%; p = 0.05), had longer hospitalisation (8 +/- 0.5 vs. 16 +/- 4 days; p = 0.01) and higher rate for respiratory distress syndrome (7% vs. 27%; p = 0.001). CONCLUSION: There is a significant increase in the incidence of GDM in twin pregnancies versus singleton pregnancies. The risk is highest in African-American and young women.

Sequential changes in antiangiogenic factors in early pregnancy and risk of developing preeclampsia.

Concentrations of soluble fms-like tyrosine kinase 1 (sFlt1) and soluble endoglin (sEng) increase in maternal blood with the approach of clinical preeclampsia. Although alterations in these circulating antiangiogenic factors herald the signs and symptoms of preeclampsia, in vitro studies suggest they may also play a role in regulating early placental cytotrophoblast functions. Early pregnancy changes in sFlt1 and sEng may thus identify women destined to develop preeclampsia. We performed a nested case-control study of 39 women who developed preeclampsia and 147 contemporaneous normotensive controls each with serum collected in the first (11 to 13 weeks of gestation) and second (17 to 20 weeks) trimesters. Whereas levels of sFlt1 and sEng at 11 to 13 weeks were similar between cases and controls (sFlt1: 3.5+/-0.3 ng/mL versus 3.0+/-0.1, P=0.14; sEng 6.9+/-0.3 ng/mL versus 6.6+/-0.2, P=0.37, respectively), at 17 to 20 weeks both were elevated in the women destined to develop preeclampsia (sFlt1: 4.1+/-0.5 ng/mL versus 3.1+/-0.1, P<0.05; sEng, 6.4+/-0.4 ng/mL versus 5.2+/-0.1, P<0.01). Women who developed preterm (<37 weeks) preeclampsia demonstrated even greater sequential changes: difference [delta{d}] between second and first trimester levels: dsFlt1, 0.63+/-0.91 ng/mL in preterm PE versus 0.05+/-0.15 in controls; dsEng, 0.73+/-0.77 ng/mL versus -1.32+/-0.18, P<0.01. Similar findings were noted in a cross-sectional analysis of specimens collected from the Calcium for Preeclampsia Prevention Study. In conclusion, sequential changes in antiangiogenic factors during early pregnancy may be useful for predicting preterm preeclampsia.