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Ranolazine is an anti-anginal medication given to patients with chronic angina and persistent symptoms despite medical therapy. We examined 11 491 chronic total occlusion (CTO) percutaneous coronary interventions (PCI) that were performed at 41 US and non-US centers between 2012 and 2023 in the PROGRESS-CTO Registry. Patients on ranolazine at baseline had more comorbidities, more complex lesions, lower procedural and technical success (based on univariable but not multivariable analysis), and higher incidence of major adverse cardiac events (MACE) (on both univariable and multivariable analysis).

Background: There is variability in clinical and lesion characteristics as well as techniques in chronic total occlusion (CTO) percutaneous coronary intervention (PCI)., Methods: We analyzed patient and lesion characteristics, techniques, and outcomes in 11 503 CTO-PCI procedures performed in North America (NA) and in the combined regions of Europe, Asia, and Africa from 2017 to 2023 as documented in the PROGRESS-CTO registry., Results: Eight thousand four hundred seventy-nine (74%) procedures were performed in NA. Compared with non-NA patients, NA patients were older, with higher body mass index and higher prevalence of diabetes, hypertension, dyslipidemia, family history of coronary artery disease, prior history of PCI, coronary artery bypass graft surgery and heart failure, cerebrovascular disease, and peripheral arterial disease. Their CTOs were more complex, with higher J-CTO (2.56 ± 1.22 vs 1.81 ± 1.24; P less than .001) and PROGRESS-CTO (1.29 ± 1.01 vs 1.07 ± 0.95; P less than .001) scores, longer length, and higher prevalence of proximal cap ambiguity, blunt/no stump, moderate to severe calcification, and proximal tortuosity. Retrograde (31.0% vs 22.1%; P less than .001) and antegrade dissection and re-entry (ADR) (21.2% vs 9.2%; P less than .001) were more commonly used in NA centers, along with intravascular ultrasound (69.0% vs 10.1%; P less than .001). Procedure and fluoroscopy times were longer in NA, while contrast volume and radiation dose were lower. Technical (86.7% vs 86.8%; P > .90) and procedural (85.4% vs 85.8%; P = .70) success and in-hospital major adverse cardiovascular events (MACE) (1.9% vs 1.7%; P = .40) were similar in NA and non-NA centers., Conclusions: Compared with non-NA patients, NA patients undergoing CTO PCI have more comorbidities, higher CTO lesion complexity, are more likely to undergo treatment with retrograde and ADR, and have similar technical success and MACE.

Background: The impact of peripheral artery disease (PAD) on the outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is not well studied., Methods: We analyzed the association of PAD with CTO-PCI outcomes using data from the PROGRESS-CTO registry of procedures performed at 47 centers between 2012 and 2023., Results: The prevalence of PAD among 12 961 patients who underwent CTO PCI during the study period was 13.9% (1802). PAD patients were older, more likely to be current smokers, and had higher rates of dyslipidemia, diabetes, cerebrovascular disease, hypertension, prior myocardial infarction, PCI, and coronary artery bypass graft surgery. Their PROGRESS-CTO (1.35 vs 1.22; P < .001) and J-CTO (2.63 vs 2.33; P < .001) scores were higher, lesion length was longer, and angiographic characteristics were more complex. Their access site was more likely to be bifemoral (33.6% vs 30.9%; P = .024) compared with patients with no PAD. Technical (82.9% vs 87.7%; P < .001) and procedural (80.5% vs 86.6%; P < .001) success rates were lower in patients with PAD, while the incidence of major adverse cardiovascular events (MACE) was higher (3.1% vs 1.8%; P < .001), with higher mortality (0.8% vs 0.4%; P = .034), acute myocardial infarction rate (0.9% vs 0.4%; P = .010), and perforations rate (6.6% vs 4.5%; P < .001). In multivariable analysis, PAD was associated with higher MACE (odds ratio [OR]: 1.53; 95% CI, 1.01-2.26; P = .038) and lower technical success (OR: 0.82; 95% CI, 0.69-0.99; P = .039)., Conclusions: PAD patients undergoing CTO PCI have higher comorbidity burden, more complex CTOs, higher MACE, and lower technical success.

Background: There is limited data on equipment loss or entrapment during chronic total occlusion (CTO) percutaneous coronary intervention (PCI)., Methods: We analyzed the baseline clinical and angiographic characteristics and outcomes of equipment loss/entrapment at 43 US and non-US centers between 2017 and 2023., Results: Equipment loss/entrapment was reported in 40 (0.4%) of 10 719 cases during the study period. These included guidewire entrapment/fracture (n = 21), microcatheter entrapment/fracture (n = 11), stent loss (n = 8) and balloon entrapment/fracture/rupture (n = 5). The equipment loss/entrapment cases were more likely to have moderate to severe calcification, longer lesion length, higher J-CTO and PROGRESS-CTO complications scores, and use of the retrograde approach compared with the remaining cases. Retrieval was attempted in 71.4% of the guidewire, 90.9% of the microcatheter, 100% of the stent loss, and 100% of the balloon cases, and was successful in 26.7%, 30.0%, 50%, and 40% of the cases, respectively. Procedures complicated by equipment loss/entrapment had higher procedure and fluoroscopy time, contrast volume and patient air kerma radiation dose, lower procedural (60.0% vs 85.6%, P less than .001) and technical (75.0% vs 86.8%, P = .05) success, and higher incidence of major adverse cardiac events (MACE) (17.5% vs 1.8%, P less than .001), acute MI (7.5% vs 0.4%, P less than .001), emergency coronary artery bypass graft (CABG) (2.5% vs 0.1%, P = .03), perforation (20.0% vs 4.9%, P less than .001), and death (7.5% vs 0.4%, P less than .001)., Conclusions: Equipment loss is a rare complication of CTO PCI; it is more common in complex CTOs and is associated with lower technical success and higher MACE.

Importance: Drug-coated balloons offer a potentially beneficial treatment strategy for the management of coronary in-stent restenosis. However, none have been previously evaluated or approved for use in coronary circulation in the United States., Objective: To evaluate whether a paclitaxel-coated balloon is superior to an uncoated balloon in patients with in-stent restenosis undergoing percutaneous coronary intervention., Design, Setting, and Participants: AGENT IDE, a multicenter randomized clinical trial, enrolled 600 patients with in-stent restenosis (lesion length <26 mm and reference vessel diameter >2.0 mm to ≤4.0 mm) at 40 centers across the United States between May 2021 and August 2022. One-year clinical follow-up was completed on October 2, 2023., Interventions: Participants were randomized in a 2:1 allocation to undergo treatment with a paclitaxel-coated (n = 406) or an uncoated (n = 194) balloon., Main Outcomes and Measures: The primary end point of 1-year target lesion failure-defined as the composite of ischemia-driven target lesion revascularization, target vessel-related myocardial infarction, or cardiac death-was tested for superiority., Results: Among 600 randomized patients (mean age, 68 years; 157 females [26.2%]; 42 Black [7%], 35 Hispanic [6%] individuals), 574 (95.7%) completed 1-year follow-up. The primary end point at 1 year occurred in 17.9% in the paclitaxel-coated balloon group vs 28.6% in the uncoated balloon group, meeting the criteria for superiority (hazard ratio [HR], 0.59 [95% CI, 0.42-0.84]; 2-sided P = .003). Target lesion revascularization (13.0% vs 24.7%; HR, 0.50 [95% CI, 0.34-0.74]; P = .001) and target vessel-related myocardial infarction (5.8% vs 11.1%; HR, 0.51 [95% CI, 0.28-0.92]; P = .02) occurred less frequently among patients treated with paclitaxel-coated balloon. The rate of cardiac death was 2.9% vs 1.6% (HR, 1.75 [95% CI, 0.49-6.28]; P = .38) in the coated vs uncoated balloon groups, respectively., Conclusions and Relevance: Among patients undergoing coronary angioplasty for in-stent restenosis, a paclitaxel-coated balloon was superior to an uncoated balloon with respect to the composite end point of target lesion failure. Paclitaxel-coated balloons are an effective treatment option for patients with coronary in-stent restenosis., Trial Registration: ClinicalTrials.gov Identifier: NCT04647253.

Rationale: Fever is frequently an early indicator of infection and often requires rigorous diagnostic evaluation., Objectives: This is an update of the 2008 Infectious Diseases Society of America and Society (IDSA) and Society of Critical Care Medicine (SCCM) guideline for the evaluation of new-onset fever in adult ICU patients without severe immunocompromise, now using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology., Panel Design: The SCCM and IDSA convened a taskforce to update the 2008 version of the guideline for the evaluation of new fever in critically ill adult patients, which included expert clinicians as well as methodologists from the Guidelines in Intensive Care, Development and Evaluation Group. The guidelines committee consisted of 12 experts in critical care, infectious diseases, clinical microbiology, organ transplantation, public health, clinical research, and health policy and administration. All task force members followed all conflict-of-interest procedures as documented in the American College of Critical Care Medicine/SCCM Standard Operating Procedures Manual and the IDSA. There was no industry input or funding to produce this guideline., Methods: We conducted a systematic review for each population, intervention, comparison, and outcomes question to identify the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the GRADE approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak or as best-practice statements., Results: The panel issued 12 recommendations and 9 best practice statements. The panel recommended using central temperature monitoring methods, including thermistors for pulmonary artery catheters, bladder catheters, or esophageal balloon thermistors when these devices are in place or accurate temperature measurements are critical for diagnosis and management. For patients without these devices in place, oral or rectal temperatures over other temperature measurement methods that are less reliable such as axillary or tympanic membrane temperatures, noninvasive temporal artery thermometers, or chemical dot thermometers were recommended. Imaging studies including ultrasonography were recommended in addition to microbiological evaluation using rapid diagnostic testing strategies. Biomarkers were recommended to assist in guiding the discontinuation of antimicrobial therapy. All recommendations issued were weak based on the quality of data., Conclusions: The guidelines panel was able to formulate several recommendations for the evaluation of new fever in a critically ill adult patient, acknowledging that most recommendations were based on weak evidence. This highlights the need for the rapid advancement of research in all aspects of this issue-including better noninvasive methods to measure core body temperature, the use of diagnostic imaging, advances in microbiology including molecular testing, and the use of biomarkers., Competing Interests: Supported, in part, by the Intramural Research Program of the National Institutes of Health (NIH). Dr. Weber received funding from Pfizer, Merck, PDI, and Germitec. Dr. Pastores received funding from McGraw Hill; he disclosed that he is on the advisory board for AbbVie. Dr. Van Duin received funding from the National Institute of Allergy and Infectious Diseases (Antibiotic Resistance Leadership Group UM1AI104681), the NIH, and British Society for Antimicrobial Chemotherapy; he disclosed that he is a consultant for Actavis, Tetraphase, Sanofi-Pasteur, MedImmune, Astellas, Merck, Allergan, T2Biosystems, Roche, Achaogen, Neumedicine, Shionogi, Pfizer, Entasis, QPex, Wellspring, Karius, and Utility. Dr. Patel received funding from ContraFect, TenNor Therapeutics Limited, Hylomorph, BioFire, Shionogi, IDSA, NBME, UptoDate, and the Infectious Diseases Board Review Course; she disclosed that she is a consultant for Curetis, Specific Technologies, Next Gen Diagnostics, PathoQuest, Selux Diagnostics, 1928 Diagnostics, PhAST, Torus Biosystems, Mammoth Biosciences, Qvella, and Netflix; she disclosed that she has a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Competing Interests: Dr. Weber received funding from Pfizer, Merck, PDI, and Germitec. Dr. Pastores received funding from McGraw Hill; he disclosed that he is on the advisory board for AbbVie. Dr. van Duin received funding from the National Institute of Allergy and Infectious Diseases (Antimicrobial Resistance Leadership Group UM1AI104681), the National Institutes of Health, and British Society for Antimicrobial Chemotherapy; he disclosed that he is a consultant for Actavis, Tetraphase, Sanofi-Pasteur, MedImmune, Astellas, Merck, Allergan, T2Biosystems, Roche, Achaogen, Neumedicine, Shionogi, Pfizer, Entasis, QPex, Wellspring, Karius, and Utility. Dr. Patel received funding from ContraFect, TenNor Therapeutics, Hylomorph, BioFire, Shionogi, Infectious Diseases Society of America, National Board of Medical Examiners, UptoDate, and the Infectious Diseases Board Review Course; she disclosed that she is a consultant for Curetis, Specific Technologies, Next Gen Diagnostics, PathoQuest, Selux Diagnostics, 1928 Diagnostics, PhAST Diagnostics, Torus Biosystems, Mammoth Biosciences, Qvella, and Netflix; she disclosed that she has a patent on Bordetella pertussis/parapertussis polymerase chain reaction issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Background: There is limited information on the impact of the target vessel on the procedural techniques and outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI)., Methods: We analyzed the baseline clinical and angiographic characteristics and procedural outcomes of 11,580 CTO PCIs performed between 2012 and 2022 at 44 centers., Results: The most common CTO target vessel was the right coronary artery (RCA) (53.1%) followed by the left anterior descending artery (LAD) (26.0%) and the left circumflex artery (LCX) (19.8%). RCA CTOs were longer and more complex, with a higher Japanese CTO score compared with LAD or LCX CTOs. Technical success was higher among LAD (88.8%) lesions when compared with RCA (85.7%) or LCX (85.8%) lesions (P less than .001). The incidence of major adverse cardiovascular events (MACE) was overall 1.9% (n = 220) and was similar among target vessels (P=.916). There was a tendency toward more frequent utilization of the retrograde approach for more proximal occlusions in all 3 target vessels. When compared with all other RCA lesions combined, distal RCA lesions had higher technical success (87.7% vs 85.3%; P=.048). Technical success was similar between various locations of LAD CTOs (P=.704). First/second/third obtuse marginal branch had lower technical success when compared with all other LCX lesion locations (82.7% vs 86.8%; P=.014). There was no association between MACE and CTO location in all 3 target vessels., Conclusions: LAD CTO PCIs had higher technical and procedural success rates among target vessels. The incidence of MACE was similar among target vessels and among various locations within the target vessel.

Background: Death is a rare but devastating complication of chronic total occlusion (CTO) percutaneous coronary intervention., Methods: We examined the clinical characteristics and procedural outcomes of patients who died periprocedurally in the Prospective Global Registry for the Study of CTO Interventions (PROGRESS-CTO)., Results: Of the 12 928 patients who underwent CTO percutaneous coronary intervention between 2012 and 2022, 52 (0.4%) died during the index hospitalization. Patients who died were more likely to have a history of heart failure (43% versus 28%; P =0.023). The J-CTO ([Multicenter CTO Registry of Japan]; 2.8±1.1 versus 2.4±1.3; P =0.019), PROGRESS-CTO mortality (2.6±0.9 versus 1.6±1.1; P <0.001), and PROGRESS-CTO pericardiocentesis (2.9±1.1 versus 1.9±1.3; P <0.001) scores were higher in patients who died. In these patients, the use of left ventricular assist devices was also higher (41% versus 3.5%; P <0.001), and retrograde crossing was more often the first crossing strategy (33% versus 13%; P <0.001). The cause of death was cardiac in 43 patients (83%) and noncardiac in 9 patients (17%). Complications leading to cardiac death were: tamponade in 30 patients (58%), acute myocardial infarction in 9 (17.3%), and cardiac arrest/shock in 4 (7.7%). Noncardiac causes of death were: stroke in 3 (5.8%), renal failure in 2 (3.8%), respiratory distress in 2 (3.8%), and hemorrhagic shock in 2 (3.8%)., Conclusions: Approximately 0.4% of patients who underwent CTO percutaneous coronary intervention died during the index hospitalization. The main cause of death was tamponade in 58%. PROGRESS-CTO complication scores might help in risk stratification and procedural planning in patients undergoing CTO percutaneous coronary intervention., Registration: URL: https://www., Clinicaltrials: gov; Unique Identifier: NCT02061436., Competing Interests: Disclosures Dr Alaswad is a consultant and speaker for Boston Scientific, Abbott Cardiovascular, Teleflex, and CSI. Dr Jaffer performed sponsored research: Canon, Siemens, Shockwave, Teleflex, Mercator, Boston Scientific; Consultant: Boston Scientific, Siemens, Magenta Medical, IMDS, Asahi Intecc, Biotronik, Philips, Intravascular Imaging. Equity interest—Intravascular Imaging, Inc, DurVena. Massachusetts General Hospital—licensing arrangements: Terumo, Canon, Spectrawave, for which FAJ has right to receive royalties. Dr Doshi participated in speaker’s bureau for Abbott Vascular, Boston Scientific, and Medtronic and research support from Biotronik. Dr Davies received honoraria/consulting from Medtronic, Seimens Healthineers and Asahi intec. Dr ElGuindy received consulting Honoraria from Medtronic, Boston Scientific, Asahi Intecc, Abbott; proctorship fees from Medtronic, Boston Scientific, Asahi Intecc, Terumo; and eEducational grants: Medtronic. Dr Patel received consulting Honoraria from Abbott, Medtronic, Terumo, Cardiovascular Systems, Inc. Dr Potluri is speaker in advisory board, proctor for Boston Scientific, medtronic, Abbott, Terumo, Shockwave. Dr Burke is Shareholder for Egg Medical and MHI Ventures. Dr Brilakis received consulting/speaker honoraria from Abbott Vascular, American Heart Association (associate editor Circulation), Amgen, Asahi Intecc, Biotronik, Boston Scientific, Cardiovascular Innovations Foundation (Board of Directors), ControlRad, CSI, Elsevier, GE Healthcare, IMDS, InfraRedx, Medicure, Medtronic, Opsens, Siemens, and Teleflex; research support: Boston Scientific, GE Healthcare; owner, Hippocrates LLC; shareholder: MHI Ventures, Cleerly Health, Stallion Medical. The other authors report no conflicts.

Background: Same day discharge (SDD) following chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study., Methods: We evaluated the clinical, angiographic, and procedural characteristics of patients discharged the same day versus those kept for overnight observation in the Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (PROGRESS-CTO, NCT02061436)., Results: Of the 7181 patients who underwent CTO PCI, 943 (13%) had SDD. The SDD rate increased from 3% in 2015 to 21% in 2022. Patients with SDD were less likely to have a history of heart failure (21% vs. 26%, p = 0.005), chronic lung disease (10% vs. 15%, p = 0.001), or anemia (12% vs. 19%, p < 0.001). Technical success (87% vs. 88%, p = 0.289) was similar, but in-hospital major adverse cardiovascular events (0.0% vs. 0.4%, p = 0.041) were lower in SDD. In multivariable logistic regression analysis, prior myocardial infarction odds ratio (OR): 0.71 (95% confidence interval [CI]: 0.59-0.87, p = 0.001), chronic lung disease OR: 0.64 (95% CI: 0.47-0.88, p = 0.006), and increasing procedure time OR: 0.93 (95% CI: 0.91-0.95, p < 0.001, per 10-min increase) were associated with overnight observation, while radial-only access OR: 2.45 (95% CI: 2.03-2.96, p < 0.001) had the strongest association with SDD. In the SDD, 2 (0.4%) of 514 patients were readmitted, due to retroperitoneal bleeding (n = 1) and ischemic stroke (n = 1)., Conclusion: The overall frequency of SDD after CTO PCI was 13% and has been increasing over time. SDD is feasible in select patients following CTO PCI, and radial-only access had the strongest association with SDD., (© 2023 Wiley Periodicals LLC.)

Background: There are limited data on the use of bivalirudin for chronic total occlusion (CTO) percutaneous coronary intervention (PCI)., Methods: We compared CTO-PCIs performed using bivalirudin vs unfractionated heparin in the Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (PROGRESS-CTO; NCT02061436). The primary endpoint was net adverse cardiac events (NACE), defined as major adverse cardiac events (MACE) and vascular complications., Results: Between 2012 and 2022, a total of 73 of 9723 procedures (0.75%) were performed using bivalirudin. The J-CTO score (2.4 ± 1.2 vs 2.4 ± 1.3; P=.73) and the PROGRESS-CTO score (1.4 ± 0.9 vs 1.2 ± 1.0; P=.31) were similar in both groups, and the retrograde approach was used less often in the bivalirudin group (15% vs 30%; P<.01). Procedural success (89% vs 85%; P=.35), in-hospital NACE (1.4% vs 2.1%; P>.99), incidence of MACE (0% vs 0.76%; P=.64), and vascular access complications (1.4% vs 0.9%; P=.48) were not different between the 2 groups. On multivariable analysis, use of bivalirudin was not associated with an increased risk of NACE (odds ratio, 0.99; 95% confidence interval, 0.13-7.27)., Conclusion: Bivalirudin is infrequently used during retrograde CTO-PCI. While the incidence of adverse events was similar with unfractionated heparin, larger studies are needed to assess the safety of bivalirudin.

Background: Guidewires and microcatheters are critical to the success of chronic total occlusion (CTO) percutaneous coronary intervention (PCI)., Methods: We examined equipment utilization in 11,202 CTO-PCIs performed in 10,952 patients at 42 United States (US) and non-US centers between 2012 and 2022., Results: Antegrade-only crossing was attempted in 7628 CTO-PCIs (68%) and the retrograde approach was used in 3574 CTO-PCIs (32%). The median number of guidewires used during antegrade wiring increased with lesion complexity from 3 (interquartile range [IQR], 2-4) for J-CTO score of 0 to 5 (IQR, 4-7) for J-CTO score of 5 (P<.001). Antegrade-only procedures had higher technical (90% vs 79%; P<.001) and procedural success (89% vs 77%; P<.001) compared with retrograde procedures. In antegrade-only cases, Pilot 200 (28%; Abbott Vascular) and Fielder XT (24%; Asahi Intecc) were the most frequently used guidewires, while Corsair (21%; Asahi Intecc) and Turnpike Spiral (20%; Vascular Solutions) were the most commonly used microcatheters. In retrograde cases, Sion (32%; Asahi Intecc) was the most common guidewire used, followed by Sion Black (22%; Asahi Intecc), Pilot 200 (22%), and Suoh 03 (19%; Asahi Intecc), while Corsair (16%) and Turnpike LP (11%) were the most commonly used microcatheters. The most successful guidewire for collateral crossing was the Sion (32%), followed by Sion Black (15%) and Suoh 03 (11%)., Conclusion: Polymer-jacketed guidewires are the most commonly used guidewires for antegrade wiring, while non-polymer-jacketed, torquable guidewires are the most frequently used guidewires for retrograde techniques. Turnpike and Corsair are the most commonly used microcatheters in CTO-PCI.

Background: The prevalence and outcomes of patients who presented with an acute coronary syndrome (ACS) and underwent chronic total occlusion (CTO) percutaneous coronary intervention (PCI) have received limited study., Methods: We examined the clinical characteristics and procedural outcomes of ACS patients who underwent CTO-PCI in the Prospective Global Registry for the Study of CTO Intervention (PROGRESS-CTO; NCT02061436)., Results: Of the 8826 patients who underwent CTO-PCI between 2012 and 2022 at 38 centers, 558 (6.3%) presented with ACS. ACS presentation was with non-ST-segment elevation myocardial infarction (MI) in 54%, unstable angina in 33%, and ST-segment elevation MI in 6.5%. ACS patients were older (66 ± 11 years vs 64 ± 10 years; P<.001) and had higher prevalence of comorbidities such as diabetes mellitus (48% vs 42%; P=.02), prior MI (52% vs 45%; P<.01), and lower left ventricular ejection fraction (49 ± 14% vs 51 ± 13%; P<.01). While the PROGRESS-CTO score (1.4 ± 1.0 vs 1.2 ± 1.0; P<.001) was higher in the ACS group, the J-CTO score was comparable (2.3 ± 1.2 vs 2.4 ± 1.3; P=.68). Technical success (88% vs 86%; P=.12) and the incidence of in-hospital major adverse cardiovascular event (MACE) (0.9% vs 2.1%; P=.06) and adverse events at 3-month follow-up (3.4% vs 7.2%; Kaplan-Meier log-rank P=.16) were similar between ACS and non-ACS patients, respectively., Conclusion: Approximately 6% of patients who underwent CTO-PCI presented with an ACS. Technical success, in-hospital MACE, and the incidence of adverse events up to 3 months were similar between patients who presented with vs without an ACS.

Background: Preprocedural coronary computed tomography angiography (CCTA) can be useful in procedural planning for chronic total occlusion (CTO) percutaneous coronary intervention (PCI)., Methods: We examined the clinical, angiographic and procedural characteristics and outcomes of cases with vs. without preprocedural CCTA in PROGRESS-CTO (NCT02061436). Multivariable logistic regression was used to adjust for confounding factors., Results: Of 7034 CTO PCI cases, preprocedural CCTA was used in 375 (5.3%) with increasing frequency over time. Patients with preprocedural CCTA had a higher prevalence of prior coronary artery bypass graft surgery (39% vs. 27%, p < 0.001) and angiographically unfavorable characteristics including higher prevalence of proximal cap ambiguity (52% vs. 33%, p < 0.001) and moderate/severe calcification (59% vs. 41%, p < 0.001) compared with those without CCTA. CCTA helped resolve proximal cap ambiguity in 27%, identified significant calcium not seen on diagnostic angiography in 18%, changed estimated CTO length by >5 mm in 10%, and was performed as part of initial coronary artery disease work up in 19%. CCTA cases had higher J-CTO (2.6 ± 1.2 vs. 2.3 ± 1.3, p < 0.001) and PROGRESS-CTO (1.3 ± 1.0 vs. 1.2 ± 1.0 p = 0.027) scores. After adjusting for potential confounders, cases with preprocedural CCTA had similar technical success (odds ratio [OR]: 1.18, 95% confidence interval [CI], 0.83-1.67) and incidence of major adverse cardiovascular events (OR: 1.47, 95% CI, 0.72-3.00)., Conclusion: Preprocedural CCTA was used in ~5% of CTO PCI cases. While CCTA may help with procedural planning, especially in complex cases, technical success and MACE were similar with or without CCTA., Competing Interests: Declaration of Competing Interest Dr. Jaffer: Sponsored research: Canon, Siemens, Shockwave, Teleflex, Mercator, Boston Scientific; Consultant: Boston Scientific, Siemens, Magenta Medical, IMDS, Asahi Intecc, Biotronik, Philips, Intravascular Imaging. Equity interest – Intravascular Imaging Inc., DurVena. Massachusetts General Hospital – licensing arrangements: Terumo, Canon, Spectrawave, for which FAJ has right to receive royalties. Dr. Doshi: speaker's bureau for Abbott Vascular, Boston Scientific, and Medtronic and research support from Biotronik. Dr. Alaswad: consultant and speaker for Boston Scientific, Abbott Cardiovascular, Teleflex, and CSI. Dr. Khatri: Personal Honoria for proctoring and speaking: Abbott Vascular, Asahi Intecc, Terumo, Boston Scientific. Dr. Davies: honoraria/consulting from Medtronic, Seimens Healthineers and Asahi intec. Dr. Mitul Patel: Consulting Honoraria from Abbott, Medtronic, Terumo, Cardiovascular Systems, Inc. Dr. Rinfret: Consultant for Boston Scientific, Teleflex, Abbott Vascular, Biotronik, and SoundBite Medical. Dr. Jaber: Member of the advisory board for Medtronic and has received proctoring fees from Abbott Vascular. Dr. Nicholson: reports speakers bureau, consulting, honoraria, advisory board for Abbott Vascular, Asahi Intecc, Boston Scientific, Corindus/Siemens, and Medtronic. Dr. Abi Rafeh: CTO Proctor and consultant for Boston Scientific and Abbott Vascular. Dr. ElGuindy: Consulting Honoraria: Medtronic, Boston Scientific, Asahi Intecc, Abbott; Proctorship fees: Medtronic, Boston Scientific, Asahi Intecc, Terumo; Educational grants: Medtronic. Dr. Brilakis: consulting/speaker honoraria from Abbott Vascular, American Heart Association (associate editor Circulation), Amgen, Asahi Intecc, Biotronik, Boston Scientific, Cardiovascular Innovations Foundation (Board of Directors), ControlRad, CSI, Elsevier, GE Healthcare, IMDS, InfraRedx, Medicure, Medtronic, Opsens, Siemens, and Teleflex; research support: Boston Scientific, GE Healthcare; owner, Hippocrates LLC; shareholder: MHI Ventures, Cleerly Health, Stallion Medical. Others: None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The prevalence, treatment, and outcomes of balloon undilatable lesions encountered in chronic total occlusion (CTO) percutaneous coronary intervention (PCI) have received limited study., Methods: We examined the clinical characteristics and procedural outcomes of balloon undilatable lesions in the Prospective Global Registry for the Study of CTO Intervention (PROGRESS-CTO, NCT02061436)., Results: Of 6535 CTO PCIs performed between 2012 and 2022, 558 (8.5%) lesions were balloon undilatable. In this subset, patients were older (mean age 67 ± 10 vs. 64 ± 10, p < 0.001) and had higher prevalence of comorbidities: diabetes mellitus (54% vs. 40%, p < 0.001), prior PCI (71% vs. 59%, p < 0.001), prior myocardial infarction (52% vs. 45%, p = 0.003), and prior coronary artery bypass graft surgery (44% vs. 25%, p < 0.001). The CTO lesion length was estimated to be 34 ± 23 mm, mean J-CTO score was 2.9 ± 1.1 and mean PROGRESS-CTO score was 1.4 ± 1.0. A cutting balloon was used in 27%, a scoring balloon in 15%, laser in 14%, rotational atherectomy in 28%, orbital atherectomy in 10%, intravascular lithotripsy in 1% and other modalities/approaches in 5%. Balloon undilatable lesions had lower technical success (90.9% vs. 93.8%, p = 0.007) and higher incidence of major adverse cardiovascular events (MACE) (composite of in-hospital death, acute myocardial infarction, stroke, re-PCI, emergency CABG, and pericardiocentesis) (5.0% versus 1.3%, p < 0.001)., Conclusion: Approximately 1 in 12 CTO (8.5%) lesions are balloon undilatable. Treatment of balloon undilatable lesions is associated with lower technical success and higher in-hospital MACE., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The relationship between left ventricular ejection fraction (LVEF) and the success and safety of coronary chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study., Methods: We examined the clinical characteristics and outcomes of CTO PCI in the Prospective Global Registry for the Study of CTO Intervention (PROGRESS-CTO) after stratifying patients by LVEF (≤35%, 36%-49%, and ≥50%)., Results: A total of 7827 CTO PCI procedures with LVEF data were included. Mean age was 64 ± 10 years, 81% were men, 43% had diabetes mellitus, 61% had prior PCI, 45% had prior myocardial infarction, and 29% had prior coronary artery bypass graft surgery. Technical success was similar in the three LVEF strata: 85%, 86%, and 87%, p = 0.391 for LVEF ≤35%, 36%-49%, and ≥50%, respectively. In-hospital mortality was higher in lower LVEF patients (1.1%, 0.4%, and 0.3%, respectively, p = 0.001). In-hospital major adverse cardiovascular events (MACE) were numerically higher in lower EF patients (2.7%, 2.1%, and 1.9%, p = 0.271). At a median follow-up of 2 months (interquartile range: 19-350 days), patients with lower LVEF continued to have higher mortality (4.9%, 3.2%, and 1.4%, p < 0.001) while the MACE rates were similar (9.3%, 9.6%, and 7.4%, p = 0.172)., Conclusion: CTO PCI can be performed with high technical success in patients with reduced LVEF but is associated with higher in-hospital and post-discharge mortality., (© 2022 Wiley Periodicals LLC.)

Introduction and Objectives: The hybrid algorithm was designed to assist with initial and subsequent crossing strategy selection in chronic total occlusion (CTO) percutaneous coronary interventions (PCIs). However, the success of the initially selected strategy has received limited study., Methods: We examined the impact of adherence to the hybrid algorithm recommendation for initial CTO crossing technique selection in 4178 CTO PCIs from a large multicenter registry., Results: The initial crossing strategy was concordant with the hybrid algorithm recommendation in 1833 interventions (44%). Patients in the concordant group had a similar age to those in the discordant group but a lower mean J-CTO score (2.0 ± 1.4 vs 2.8 ± 1.1; P < .01). The concordant group showed higher technical success with the first crossing strategy (68% vs 48%; P < .01) and higher overall technical success (88% vs 83%; P < .01) with no difference in the incidence of in-hospital major adverse events (1.8% vs 2.3%; P = .26). In multivariable analysis, after adjustment for age, prior myocardial infarction, prior PCI, prior coronary artery bypass grafting, J-CTO score, and scheduled CTO PCI, nonadherence to the hybrid algorithm was independently associated with lower technical success of the initial crossing strategy (odds ratio, 0.55; 95% confidence interval, 0.48-0.64; P < .01)., Conclusions: Adherence to the hybrid algorithm for initial crossing strategy selection is associated with higher CTO PCI success but similar in-hospital major adverse cardiac events., (Copyright © 2020 Sociedad Española de Cardiología. All rights reserved.)

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.

Background: The impact of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) on angina and subsequent incidence of major adverse cardiovascular event (MACE) rate remains controversial., Methods: We compared patient- reported angina change and the incidence of MACE (defined as death, myocardial infarction [MI], target-vessel revascularization) between successful vs failed CTO-PCI in 1612 patients participating in a large, multicenter registry., Results: CTO-PCI was successful in 1387 patients (86%). Compared with failed CTO-PCI, successful CTO-PCI patients were less likely to have history of heart failure (33% vs 41%; P=.02), prior MI (49% vs 62%; P<.01), or prior coronary revascularization (63% vs 71% [P=.03] for PCI and 30% vs 40% [P<.01] for coronary artery bypass graft surgery). Patients in the successful CTO-PCI group had lower J-CTO scores (2.4 ± 1.3 vs 3.1 ± 1.1; P<.01) and lower PROGRESS-CTO Complications scores (1.1 ± 1.0 vs 1.6 ± 1.0; P<.01). After a mean follow-up of 181 ± 153 days, patients with successful PCI were more likely to have angina improvement (83% vs 38%; P<.01) and had lower incidence of 1-year MACE (8% vs 15%; P<.01), death (3% vs 7%; P<.01), and MI (2% vs 4%; P=.02). On multivariable analysis, however, CTO-PCI success was not independently associated with MACE., Conclusion: Compared with failed CTO-PCI, successful CTO-PCI is associated with better angina improvement and lower incidence of MACE (on univariable analysis) during follow-up.

Background: When crossing into the distal true lumen fails during chronic total occlusion (CTO) percutaneous coronary intervention (PCI), subintimal plaque modification (SPM) is often performed to restore antegrade flow and facilitate subsequent lesion recanalization., Methods: Between January 2012 and May 4, 2019, 4,659 CTO PCIs were included in the PROGRESS-CTO registry, of which 935 (20%) had a prior unsuccessful attempt. Of those 935 patients, 119 (13%) had prior SPM. We analyzed the outcomes of the 58 SPM procedures for which data were available, as well as the outcomes of the 60 subsequent CTO PCI attempts., Results: Mean patient age was 67 ± 9 years and 86% were men. Patients had high prevalence of cardiovascular risk factors such as dyslipidemia (91%), hypertension (93%) diabetes (48%), prior PCI (61%), and prior coronary artery bypass graft surgery (47%). The target CTO lesions often had proximal cap ambiguity (54%), moderate/severe calcification (73%), moderate/severe tortuosity (63%), and high J-CTO score (mean 3.2 ± 1.1). The technical and procedural success of subsequent CTO PCI were high (83% for both) with an acceptable rate of in-hospital major adverse cardiovascular events (3.3%). Technical and procedural success were higher for repeat attempts that were performed ≥60 days after the index CTO PCI (94% vs. 69%, p = .015). Median (interquartile range) subsequent procedure time was 147 (100, 215) min, contrast volume was 185 (150, 260) ml, and air kerma radiation dose was 2.5 (1.4, 4.2) Gray., Conclusion: Repeat CTO PCI attempts after SPM are associated with high likelihood for successful revascularization with acceptable risks., (© 2019 Wiley Periodicals, Inc.)

Background: The impact of intravascular ultrasound (IVUS) utilization for stent optimization on the long-term outcomes in chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study., Methods: We examined the outcomes of CTO-PCI with and without IVUS use for stent optimization in 922 CTO-PCIs performed between 2012 and 2019 at 12 United States centers. Major adverse cardiac event (MACE) was defined as the composite of cardiac death, acute coronary syndrome, and target-vessel revascularization., Results: IVUS was used in 344 procedures (37%) for stent optimization. Mean patient age was 65 ± 10 years and 83% were men. Patients in the IVUS group were less likely to have a prior myocardial infarction (39% vs 50%; P<.01), more likely to undergo right coronary artery CTO-PCI (49% vs 55%; P=.01), and had higher mean J-CTO score (2.6 ± 1.1 vs 2.4 ± 1.2; P=.04). The final crossing strategy in patients in the IVUS group was less likely to be antegrade wire escalation (54% vs 57%) and more likely to be retrograde (29% vs 21%; P<.01). Median follow-up was 141 days (interquartile range, 30-365 days). The incidence of 12-month MACE was similar in the IVUS and no-IVUS groups (20.3% vs 18.3%; log-rank P=.67)., Conclusion: IVUS was used for stent optimization in approximately one-third of CTO-PCIs. Despite higher lesion complexity in the IVUS group, the incidence of MACE was similar during follow-up.

Background: Catheter-based renal denervation has significantly reduced blood pressure in previous studies. Following a positive pilot trial, the SPYRAL HTN-OFF MED (SPYRAL Pivotal) trial was designed to assess the efficacy of renal denervation in the absence of antihypertensive medications., Methods: In this international, prospective, single-blinded, sham-controlled trial, done at 44 study sites in Australia, Austria, Canada, Germany, Greece, Ireland, Japan, the UK, and the USA, hypertensive patients with office systolic blood pressure of 150 mm Hg to less than 180 mm Hg were randomly assigned 1:1 to either a renal denervation or sham procedure. The primary efficacy endpoint was baseline-adjusted change in 24-h systolic blood pressure and the secondary efficacy endpoint was baseline-adjusted change in office systolic blood pressure from baseline to 3 months after the procedure. We used a Bayesian design with an informative prior, so the primary analysis combines evidence from the pilot and Pivotal trials. The primary efficacy and safety analyses were done in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT02439749., Findings: From June 25, 2015, to Oct 15, 2019, 331 patients were randomly assigned to either renal denervation (n=166) or a sham procedure (n=165). The primary and secondary efficacy endpoints were met, with posterior probability of superiority more than 0·999 for both. The treatment difference between the two groups for 24-h systolic blood pressure was -3·9 mm Hg (Bayesian 95% credible interval -6·2 to -1·6) and for office systolic blood pressure the difference was -6·5 mm Hg (-9·6 to -3·5). No major device-related or procedural-related safety events occurred up to 3 months., Interpretation: SPYRAL Pivotal showed the superiority of catheter-based renal denervation compared with a sham procedure to safely lower blood pressure in the absence of antihypertensive medications., Funding: Medtronic., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The impact of peripheral artery disease (PAD) in patients undergoing chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study. We reviewed 3999 CTO PCIs performed in 3914 patients between 2012 and 2018 at 25 centers, 14% of whom had a history of PAD. We compared the clinical and angiographic characteristics and procedural outcomes of patients with versus without history of PAD. Patients with PAD were older (67 ± 9 vs 64 ± 10 years, P < .001) and had a higher prevalence of cardiovascular risk factors. They also had more complex lesions as illustrated by higher Japanese CTO score (2.7 ± 1.2 vs 2.4 ± 1.3, P < .001). In patients with PAD, the final crossing technique was less often antegrade wire escalation (40% vs 51%, P < .001) and more often the retrograde approach (23 vs 20%, P < .001) and antegrade dissection/reentry (20% vs 16%, P < .001). Technical success was similar between the 2 study groups (84% vs 87%, P = .127), but procedural success was lower for patients with PAD (81% vs 85%, P = .015). The incidence of in-hospital major adverse cardiac events was higher among patients with PAD (3% vs 2%, P = .046). In conclusion, patients with PAD undergoing CTO PCI have more comorbidities, more complex lesions, and lower procedural success.

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., (Copyright © 2020 American College of Cardiology Foundation. All rights reserved.)

Background: During chronic total occlusion (CTO) percutaneous coronary intervention (PCI), sometimes non-CTO lesions are also treated., Methods: We compared the clinical and procedural characteristics and outcomes of CTO PCIs with and without concomitant treatment of a non-CTO lesion in a contemporary multicenter CTO registry., Results: Of the 3598 CTO PCIs performed at 21 centers between 2012 and 2018, 814 (23%) also included PCI of at least one non-CTO lesion. Patients in whom non-CTO lesions were treated were older (65 ± 10 vs. 64 ± 10 years, p = 0.03), more likely to present with an acute coronary syndrome (32% vs. 23%, p < 0.01), and less likely to undergo PCI of a right coronary artery (RCA) CTO (46% vs. 58%, p < 0.01). The most common non-CTO lesion location was the left anterior descending artery (31%), followed by the circumflex (29%) and the RCA (25%).Combined non-CTO and CTO-PCI procedures had similar technical (88% vs. 87%, p = 0.33) and procedural (85% vs. 85%, p = 0.74) success and major in-hospital complication rates (3.4% vs. 2.7%, p = 0.23), but had longer procedure duration (131 [88, 201] vs. 117 [75, 179] minutes, p < 0.01), higher patient air kerma radiation dose (3.0 [1.9, 4.8] vs. 2.8 [1.5, 4.6] Gray, p < 0.01) and larger contrast volume (300 [220, 380] vs. 250 [180, 350] ml, p < 0.01)., Conclusions: Combined CTO PCI with PCI of non-CTO lesions is associated with similar success and major in-hospital complication rates compared with cases in which only CTOs were treated, but requires longer procedure duration and higher radiation dose and contrast volume., (Copyright © 2019 Elsevier B.V. All rights reserved.)

There is limited data on the use of atherectomy during chronic total occlusion (CTO) percutaneous coronary intervention (PCI). We compared the clinical and procedural characteristics and outcomes of CTO PCIs performed with or without atherectomy in a contemporary multicenter CTO PCI registry. Between 2012 and 2018, 3,607 CTO PCIs were performed at 21 participating centers. Atherectomy was used in 117 (3.2%) cases: rotational atherectomy in 105 cases, orbital atherectomy in 8, and both in 4 cases. Patients in whom atherectomy was used, were older (68 ± 8 vs 64 ± 10 years, p <0.0001) and had higher Japan-chronic total occlusion score (3.0 ± 1.2 vs 2.4 ± 1.3, p <0.0001). CTO PCI cases in which atherectomy was used had similar technical (91% vs 87%, p = 0.240) and procedural (90% vs 85%, p = 0.159) success and in-hospital major adverse cardiac event (4% vs 3%, p = 0.382) rates. However, atherectomy cases were associated with higher rates of donor vessel injury (4% vs 1%, p = 0.031), tamponade requiring pericardiocentesis (2.6% vs 0.4%, p = 0.012) and more often required use of a left ventricular assist device (9% vs 5%, p = 0.031). Atherectomy cases were associated with longer procedural duration (196 [141, 247] vs 119 [76, 180] minutes, p <0.0001), and higher patient air kerma radiation dose (3.6 [2.5, 5.6] vs 2.8 [1.6, 4.7] Gray, p = 0.001). In conclusion, atherectomy is currently performed in approximately 3% of CTO PCI cases and is associated with similar technical and procedural success and overall major adverse cardiac event rates, but higher risk for donor vessel injury and tamponade., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Frequent laboratory testing may be necessary at times for critically ill patients. However, the practice of indiscriminate laboratory test ordering is common., Purpose: The purpose of this quality improvement project was to assess the effectiveness of the acute care nurse practitioner (ACNP) in reducing the number of unwarranted laboratory tests ordered for ICU patients. To determine whether the presence of an ACNP would make a difference, an ACNP was present on daily ICU multidisciplinary rounds to facilitate the discussion of the laboratory testing needs for each patient for the following 24-hour period., Conclusions: Eighty-one patients were enrolled in the project, 41 in the comparison and 40 in the intervention group. No significant differences were noted between the two groups. The project demonstrated that although there was an increase in tests ordered for the intervention group, the increase was brought about by an increase in specific individual tests rather than an increase in panels of laboratory tests. A reduction in patient cost was observed for the number of tests ordered. No increase in adverse events was noted., Implications for Practice: Acute care nurse practitioner presence on multidisciplinary rounds may be an effective method to change the practice toward the ordering of tests based on clinical indication.

Coronary artery disease and acute myocardial infarction are complex traits in which there has been recent research to identify the principal genes that engender susceptibility or provide protection. Although there has been exceptional progress in the technology, which now allows genotyping of hundreds of thousands of single-nucleotide polymorphisms in each individual, there remains a pattern of inconsistency in the studies performed to date, in part owing to the difficulties in defining cases and controls. In this paper, salient issues to facilitate research in this important field are reviewed.

Despite an increased knowledge of risk factors for atherosclerotic heart disease, it remains nearly endemic in Western society. Despite the high penetrance, only a fraction of those with the disease progress to develop a frank myocardial infarction (MI). Over the past decade, it has become clear that inflammation plays an important role in the pathogenesis of MI. Inflammatory arterial disease therefore may be a better term for the subset of patients that develop the serious adverse consequences related to the rupture of the intracoronary plaque. Using newer molecular techniques such as high-throughput SNP analysis, genome-wide scanning, and enriched pedigree analysis, many of the specific mechanisms underlying the inflammatory milieu involved in this transition have been elucidated and may help identify those at risk for the adverse events associated with atherosclerotic disease.

This study examined the association of single nucleotide polymorphisms in 4 candidate genes in a cohort of subjects with aspirin resistance. Aspirin resistance was significantly associated with genetic variation in the platelet surface adenosine 5-diphosphate receptor gene P2Y1.

A 50-year-old African American woman presented with bilateral lower extremity pain, a history of falls during the past several months, and personality and behavior changes. She had been in good health until approximately 5 months before admission, when she began to fall with increasing frequency, often while going down a flight of stairs. She described these falls as her "legs giving out" and feeling very heavy and unsteady. There was no head trauma or loss of consciousness. Her daughter noticed that her gait had become somewhat unsteady during the last several months. Her family also noted a change in her personality at this time. Previously, she had been a very tidy person who took great care with her appearance, who was working as a customer service representative. However, she had become less social and very withdrawn. She had been observed putting on dirty clothes after showering, as well as eating constantly. The patient denied any fevers, chills, night sweats, headaches, vision changes, or tinnitus. She also denied any rashes, muscle pain, or intolerance to heat or cold. There was no history of seizure disorder or depression. Her past medical history was notable only for hypertension and being a passenger in a motor vehicle crash 1 year before admission. She denied any alcohol, tobacco, or illicit drug use, and had no travel history other than coming to the United States, as she was originally from Trinidad. On physical examination, she was a moderately obese African American woman with a flat affect, psychomotor slowing, and alopecia of the scalp. She was alert and oriented to person, place, and time, but had a score of 26 out of 30 on the Mini-Mental State Examination. She lost points only for recall; she had no difficulty with serial 7s. Her cranial nerves were intact and her speech was fluent, although sparse, and she did not make any paraphasic errors. Her muscle strength was 5/5 in both the upper and lower extremities. Reflexes were 2+ in the upper extremities and 1+ in the lower extremities, and toes were downgoing bilaterally. She had intact sensation to light touch and pinprick, but markedly diminished proprioception of her lower extremities bilaterally. She had a wide-based gait with a positive Romberg sign and was markedly ataxic. Rectal examination yielded a positive guaiac test with brown stool, normal tone, and no masses. The remainder of the physical examination was normal. Laboratory studies revealed pancytopenia with a hematocrit of 22.7% and a mean corpuscular volume of 118.2 fL. A peripheral smear that was performed on admission, prior to transfusion, revealed macrocytic red cells and hypersegmented neutrophils.