Predicting Successful Chronic Total Occlusion Crossing With Primary Antegrade Wiring Using Machine Learning.

BACKGROUND: There is limited data on predicting successful chronic total occlusion crossing using primary antegrade wiring (AW). OBJECTIVE: The aim of this study was to develop and validate a machine learning (ML) prognostic model for successful chronic total occlusion crossing using primary AW. METHODS: We used data from 12,136 primary AW cases performed between 2012 and 2023 at 48 centers in the PROGRESS CTO registry (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention; NCT02061436) to develop 5 ML models. Hyperparameter tuning was performed for the model with the best performance, and the SHAP (SHapley Additive exPlanations) explainer was implemented to estimate feature importance. RESULTS: Primary AW was successful in 6,965 cases (57.4%). Extreme gradient boosting was the best performing ML model with an average area under the receiver-operating characteristic curve of 0.775 (± 0.010). After hyperparameter tuning, the average area under the receiver-operating characteristic curve of the extreme gradient boosting model was 0.782 in the training set and 0.780 in the testing set. Among the factors examined, occlusion length had the most significant impact on predicting successful primary AW crossing followed by blunt/no stump, presence of interventional collaterals, vessel diameter, and proximal cap ambiguity. In contrast, aorto-ostial lesion location had the least impact on the outcome. A web-based application for predicting successful primary AW wiring crossing is available online (PROGRESS-CTO website) (https://www.progresscto.org/predict-aw-success). CONCLUSIONS: We developed an ML model with 14 features and high predictive capacity for successful primary AW in chronic total occlusion percutaneous coronary intervention.

Geographic diversity in chronic total occlusion percutaneous coronary intervention: insights from the PROGRESS-CTO registry.

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.

Ranolazine in chronic total occlusion percutaneous coronary intervention.

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).

Retrograde chronic total occlusion percutaneous coronary intervention via ipsilateral collaterals.

BACKGROUND: There is limited data on retrograde chronic total occlusion (CTO) percutaneous coronary intervention (PCI) via ipsilateral epicardial collaterals (IEC). AIMS: To compare the clinical and angiographic characteristics, and outcomes of retrograde CTO PCI via IEC versus other collaterals in a large multicenter registry. METHODS: Observational cohort study from the Prospective Global registry for the study of Chronic Total Occlusion Intervention (PROGRESS-CTO). RESULTS: Of 4466 retrograde cases performed between 2012 and 2023, crossing through IEC was attempted in 191 (4.3%) cases with 50% wiring success. The most common target vessel in the IEC group was the left circumflex (50%), in comparison to other retrograde cases, where the right coronary artery was most common (70%). The Japanese CTO score was similar between the two groups (3.13 ± 1.23 vs. 3.06 ± 1.06, p = 0.456); however, the IEC group had a higher Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (PROGRESS-CTO) score (1.95 ± 1.02 vs. 1.27 ± 0.92, p < 0.0001). The most used IEC guidewire was the SUOH 03 (39%), and the most frequently used microcatheter was the Caravel (43%). Dual injection was less common in IEC cases (66% vs. 89%, p < 0.0001). Technical (76% vs. 79%, p = 0.317) and procedural success rates (74% vs. 79%, p = 0.281) were not different between the two groups. However, IEC cases had a higher procedural complications rate (25.8% vs. 16.4%, p = 0.0008), including perforations (17.3% vs. 9.0%, p = 0.0001), pericardiocentesis (3.1% vs. 1.2%, p = 0.018), and dissection/thrombus of the donor vessel (3.7% vs. 1.2%, p = 0.002). CONCLUSION: The use of IEC for retrograde CTO PCI was associated with similar technical and procedural success rates when compared with other retrograde cases, but higher incidence of periprocedural complications.

Interventional cardiologists' perspectives and knowledge towards artificial intelligence.

BACKGROUND: Artificial intelligence (AI) is increasingly utilized in interventional cardiology (IC) and holds the potential to revolutionize the field. METHODS: We conducted a global, web-based, anonymous survey of IC fellows and attendings to assess the knowledge and perceptions of interventional cardiologists regarding AI use in IC. RESULTS: A total of 521 interventional cardiologists participated in the survey. The median age range of participants was 36 to 45 years, most (51.5%) practice in the United States, and 7.5% were women. Most (84.7%) could explain well or somehow knew what AI is about, and 63.7% were optimistic/very optimistic about AI in IC. However, 73.5% believed that physicians know too little about AI to use it on patients and most (46.1%) agreed that training will be necessary. Only 22.1% were currently implementing AI in their personal clinical practice, while 60.6% estimated implementation of AI in their practice the next 5 years. Most agreed that AI will increase diagnostic efficiency, diagnostic accuracy, treatment selection, and healthcare expenditure, and decrease medical errors. The most tried AI-powered tools were image analysis (57.3%), ECG analysis (61.7%), and AI-powered algorithms (45.9%). Interventional cardiologists practicing in academic hospitals were more likely to have AI tools currently implemented in their clinical practice and to use them, women had a higher likelihood of expressing concerns regarding AI, and younger interventional cardiologists were more optimistic about AI integration in IC. CONCLUSIONS: Our survey suggests a positive attitude of interventional cardiologists regarding AI implementation in the field of IC.

Use of plaque modification microcatheters during percutaneous coronary interventions for chronic total occlusion: insights from the PROGRESS-CTO Registry.

Plaque modification microcatheters (PM) (Tornus [Asahi] and Turnpike Gold [Teleflex]) are devices that are mainly used to modify the cap or lesion and maintain good support in chronic total occlusion (CTO) percutaneous coronary artery intervention (PCI). We evaluated the frequency of use and outcomes of plaque modification microcatheters in an international multicenter registry. Plaque modification microcatheters were utilized in 242 cases (1.6%: Tornus in 51% and Turnpike Gold in 49%) with decreasing frequency over time (P-for-trend: 0.007 and 0.035, respectively). Technical and procedural success and the incidence of major cardiac adverse events were similar with Tornus and Turnpike Gold use. PM are infrequently utilized in CTO-PCI and are associated with high success and acceptable complication rates.

Emergency coronary artery bypass surgery after chronic total occlusion percutaneous coronary intervention: Insights from the PROGRESS-CTO registry.

BACKGROUND: Emergency coronary artery bypass surgery (eCABG) is a serious complication of chronic total occlusion (CTO) percutaneous coronary artery intervention (PCI). METHODS: We examined the incidence and outcomes eCABG among 14,512 CTO PCIs performed between 2012 and 2023 in a large multicenter registry. RESULTS: The incidence of eCABG was 0.12% (n = 17). Mean age was 68 ± 6 years and 69% of the patients were men. The most common reason for eCABG was coronary perforation (70.6%). eCABG patients had larger target vessel diameter (3.36 ± 0.50 vs. 2.90 ± 0.52; p = 0.003), were more likely to have moderate/severe calcification (85.7% vs. 45.8%; p = 0.006), side branch at the proximal cap (91.7% vs. 55.4%; p = 0.025), and balloon undilatable lesions (50% vs. 7.4%; p = 0.001) and to have undergone retrograde crossing (64.7% vs. 30.8%, p = 0.006). eCABG cases had lower technical (35.3% vs. 86.7%; p < 0.001) and procedural (35.3% vs. 86.7%; p < 0.001) success and higher in-hospital mortality (35.3% vs. 0.4%; p < 0.001), coronary perforation (70.6% vs. 4.6%; p < 0.001), pericardiocentesis (47.1% vs. 0.8%; p < 0.001), and major bleeding (11.8% vs. 0.5%; p < 0.001). CONCLUSIONS: The incidence of eCABG after CTO PCI was 0.12% and associated with high in-hospital mortality (35%). Coronary perforation was the most common reason for eCABG.

Predictors of successful primary antegrade wiring in chronic total occlusion percutaneous coronary intervention.

BACKGROUND: Antegrade wiring is the most commonly used chronic total occlusion (CTO) crossing technique. METHODS: Using data from the PROGRESS CTO registry (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention; Clinicaltrials.gov identifier: NCT02061436), we examined the clinical and angiographic characteristics and procedural outcomes of CTO percutaneous coronary interventions (PCIs) performed using a primary antegrade wiring strategy. RESULTS: Of the 13 563 CTO PCIs performed at 46 centers between 2012 and 2023, a primary antegrade wiring strategy was used in 11 332 (83.6%). Upon multivariable logistic regression analysis, proximal cap ambiguity (odds ratio [OR]: 0.52; 95% CI, 0.46-0.59), side branch at the proximal cap (OR: 0.85; 95% CI, 0.77-0.95), blunt/no stump (OR: 0.52; 95% CI: 0.47-0.59), increasing lesion length (OR [per 10 mm increase]: 0.79; 95% CI, 0.76-0.81), moderate to severe calcification (OR: 0.73; 95% CI, 0.66-0.81), moderate to severe proximal tortuosity (OR: 0.67; 95% CI, 0.59-0.75), bifurcation at the distal cap (OR: 0.66; 95% CI, 0.59-0.73), left anterior descending artery CTO (OR [vs right coronary artery]: 1.44; 95% CI, 1.28-1.62) and left circumflex CTO (OR [vs right coronary artery]: 1.22; 95% CI, 1.07-1.40), non-in-stent restenosis lesion (OR: 0.56; 95% CI, 0.49-0.65), and good distal landing zone (OR: 1.18; 95% CI, 1.06-1.32) were independently associated with primary antegrade wiring crossing success. CONCLUSIONS: The use of antegrade wiring as the initial strategy was high (83.6%) in our registry. We identified several parameters associated with primary antegrade wiring success.

Iso-osmolar vs low-osmolar contrast agents for coronary optical coherence tomography: a blinded prospective randomized controlled study.

BACKGROUND: The impact of contrast type on coronary optical coherence tomography (OCT) imaging has received limited research. METHODS: We conducted a blinded, prospective, single-center, randomized, controlled crossover study comparing iso-osmolar contrast media (IOCM) with low-osmolar contrast media (LOCM) in patients undergoing clinically indicated coronary OCT imaging. Patients were randomly assigned to undergo OCT imaging with either IOCM or LOCM as the initial contrast medium. Following a washout period, a second run of OCT imaging of the same coronary vessel was performed using the other contrast medium. RESULTS: A total of 62 patients were randomized to IOCM first (n = 31) or LOCM first (n = 31). Mean patient age was 65.9 ± 11.2 years and 74.2% were male, with high prevalence of dyslipidemia (82.3%) and prior myocardial infarction (41.9%). Percutaneous coronary intervention was performed in 60 cases (96.8%) and the left anterior descending artery was the most common target vessel (53.3%). The contrast volume used for OCT imaging was similar for IOCM and LOCM (8.0 [6.9, 9.0] mL vs 8.0 [6.7, 9.0] mL; P = .89), as was the length of clear OCT images (70.0 [62.8, 74.0] mm for IOCM vs 70.0 [64.0, 74.0] mm for LOCM; P = .65). Electrocardiographic changes were observed in 11 runs with IOCM (ventricular repolarization changes in 9 runs and premature ventricular contractions [PVCs] in 2 runs) vs 12 runs with LOCM (ventricular repolarization changes in 9 runs and PVCs in 3 runs). CONCLUSIONS: The use of IOCM in coronary OCT is associated with similar contrast volume and clear imaging length when compared with LOCM.

Update on chronic total occlusion percutaneous coronary intervention.

Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) continues to evolve. This review summarizes recent publications categorized by outcomes, techniques, complications, and ongoing studies in this rapidly growing area.

Racial disparities in chronic total occlusion percutaneous coronary interventions: insights from the PROGRESS-CTO registry.

OBJECTIVES: There is limited data on race and outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI). The authors sought to evaluate CTO PCI techniques and outcomes in different racial groups. METHODS: We examined the baseline characteristics and procedural outcomes of 11 806 CTO PCIs performed at 44 US and non-US centers between 2012 and March 2023. In-hospital major adverse cardiac events (MACE) included death, myocardial infarction, repeat target-vessel revascularization, pericardiocentesis, cardiac surgery, and stroke prior to discharge. RESULTS: The most common racial group was White (84.5%), followed by Black (5.7%), "Other" (3.9%), Hispanic (2.9%), Asian (2.4%), and Native American (0.7%). There were significant differences in the baseline characteristics between different racial groups. When compared with non-White patients, the retrograde approach and antegrade dissection re-entry were more likely to be the successful crossing strategies in White patients without any significant differences in technical success (86.4% vs 86.4%; P = .93), procedural success (84.8% vs 85.0%; P = .79), and in-hospital MACE (2.0% vs 1.5%; P = .15) between the 2 groups. The technical success rate was significantly higher in the "Other" racial group (91.0% vs 86.4% in White, 86.9% in Asian, 84.5% in Black, 84.5% in Hispanic, and 83.3% in Native American; P = .03) without any significant differences in procedural success or in-hospital MACE rates between the groups. CONCLUSIONS: Despite differences in baseline characteristics and procedural techniques, the procedural success and in-hospital MACE of CTO PCI were not significantly different between most racial groups.

Enhanced Risk Stratification for Children and Young Adults with B-Cell Acute Lymphoblastic Leukemia: A Children's Oncology Group Report.

Current strategies to treat pediatric acute lymphoblastic leukemia rely on risk stratification algorithms using categorical data. We investigated whether using continuous variables assigned different weights would improve risk stratification. We developed and validated a multivariable Cox model for relapse-free survival (RFS) using information from 21199 patients. We constructed risk groups by identifying cutoffs of the COG Prognostic Index (PICOG) that maximized discrimination of the predictive model. Patients with higher PICOG have higher predicted relapse risk. The PICOG reliably discriminates patients with low vs. high relapse risk. For those with moderate relapse risk using current COG risk classification, the PICOG identifies subgroups with varying 5-year RFS. Among current COG standard-risk average patients, PICOG identifies low and intermediate risk groups with 96% and 90% RFS, respectively. Similarly, amongst current COG high-risk patients, PICOG identifies four groups ranging from 96% to 66% RFS, providing additional discrimination for future treatment stratification. When coupled with traditional algorithms, the novel PICOG can more accurately risk stratify patients, identifying groups with better outcomes who may benefit from less intensive therapy, and those who have high relapse risk needing innovative approaches for cure.

Radiation dose during contemporary percutaneous coronary interventions for chronic total occlusion: insights from the PROGRESS-CTO registry.

Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is associated with high radiation doses. In this manuscript, we examined the contemporary trends and determinants of radiation dose in the PROGRESS CTO (Prospective Global Registry for the Study of CTO Intervention; Clinicaltrials.gov identifier: NCT02061436) registry. Radiation dose during CTO PCI did not change significantly since 2020, highlighting the need for innovation and operator education to further maintain radiation safety.

Burnout in cardiology: a narrative review.

The frequency of burnout is rising among cardiologists, affecting not only their well-being but also the quality of patient care. Computerization of practice, bureaucracy, excessive workload, lack of control/autonomy, hostile and hectic work environments, insufficient income, and work life imbalance are the main categories listed as contributing factors to cardiologists' burnout. Organization- and physician-directed interventions can be impactful; however, the effectiveness and feasibility of these interventions have rarely been assessed in cardiology. This review summarizes recent publications on burnout in cardiology, discusses the contributing factors and implications of burnout on physicians' health and patient safety, and explores possible interventions.

Equipment entrapment/loss during chronic total occlusion percutaneous coronary intervention.

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.

Validation of the J-Channel Score for retrograde channel crossing in the PROGRESS-CTO registry.

Successful collateral channel (CC) crossing is essential for the success of retrograde chronic total occlusion (CTO) percutaneous coronary intervention (PCI). Based on the Japanese CTO PCI expert registry, the J-Channel score was developed to predict CC crossing. We examined the performance of the J-Channel score in patients who underwent retrograde CTO-PCI at 31 centers between 2013-2023 as part of the Prospective Global Registry for the Study of CTO Intervention (PROGRESS-CTO). We observed an association between successful CC crossing and the J-Channel score, its predictive efficacy was modest for both wire and microcatheter crossing.

Comparative Analysis of Polymer Versus Non-Polymer Jacketed Wires in Chronic Total Occlusion Percutaneous Coronary Intervention.

There is significant variation in wire utilization patterns for chronic total occlusion (CTO) percutaneous coronary intervention. This study aimed to compare the outcomes of polymer-jacketed wires (PJWs) versus non-PJWs in anterograde procedures. We analyzed clinical and angiographic characteristics, and procedural outcomes of 7,575 anterograde CTO percutaneous coronary interventions that were performed at 47 centers between 2012 and 2023. Cases in which PJWs were exclusively used were classified in the PJW group, whereas cases where at least one non-PJW was employed were classified in the non-PJW group. Study end points were as follows: technical success, coronary perforation, major adverse cardiac event. PJWs were exclusively used in 3,481 cases (46.0%). These cases had lower prevalence of proximal cap ambiguity, blunt stump, and moderate/severe calcification. They also had lower Japanese CTO (J-CTO), Prospective Global Registry for the Study of Chronic Total Occlusion (PROGRESS-CTO), and PROGRESS-CTO complications scores, higher technical success (94.3% vs 85.7%, p <0.001), and lower perforation rates (2.2% vs 3.2%, p = 0.013). Major adverse cardiac event rates did not differ between groups (1.3% vs 1.5%, p = 0.53). Exclusive use of PJWs was independently associated with higher technical success in both the multivariable (odds ratio [OR] 2.66, 95% confidence interval [CI] 2.13 to 3.36, p <0.001) and inverse probability of treatment weight analysis (OR 2.43, 95% CI 2.04 to 2.89, p <0.001). Exclusive use of PJWs was associated with lower risk of perforation in the multivariable analysis (OR 0.69, 95% CI 0.49 to 0.95, p = 0.02), and showed a similar trend in the inverse probability of treatment weight analysis (OR 0.77, 95% CI 0.57 to 1.04, p = 0.09). Exclusive use of PJWs is associated with higher technical success and lower perforation risk in this non-randomized series of patients.

International survey of chronic total occlusion percutaneous coronary intervention operators.

BACKGROUND: Contemporary chronic total occlusion (CTO) percutaneous coronary intervention (PCI) practice has received limited study. AIM: To examine the contemporary CTO PCI practice. METHODS: We performed an online, anonymous, international survey of CTO PCI operators. RESULTS: Five hundred forty-five CTO PCI operators and 190 interventional cardiology fellows with an interest in CTO PCI participated in this survey. Almost half were from the United States (41%), most (93%) were men, and the median h/week spent in the hospital was 58. Median annual case numbers were 205 (150-328) for PCIs and 20 (5-50) for CTO PCIs. Almost one-fifth (17%) entered CTO cases into registries, such as PROGRESS-CTO (55%) and EuroCTO (20%). More than one-third worked at academic institutions (39%), 31% trained dedicated CTO fellows, and 22% proctored CTO PCI. One-third (34%) had dedicated CTO PCI days. Most (51%) never discharged CTO patients the same day, while 17% discharged CTO patients the same day >50% of the time. After successful guidewire crossing, 38% used intravascular imaging >90% of the time. Most used CTO scores including J-CTO (81%), PROGRESS-CTO (35%), and PROGRESS-CTO complications scores (30%). Coronary artery perforation was encountered within the last month by 19%. On a scale of 0-10, the median comfort levels in treating coronary artery perforation were: covered stents 8.8 (7.0-10), coil embolization 5.0 (2.1-8.5), and fat embolization 3.7 (0.6-7.3). Most (51%) participants had a complication cart/kit and 25% conducted regular complication drills with catheterization laboratory staff. CONCLUSION: Contemporary CTO PCI practices vary widely. Further research on barriers to following the guiding principles of CTO PCI may improve patient outcomes.

tRNA-derived fragments are altered in diabetes.

AIMS: Maternally inherited diabetes and deafness (MIDD) is a rare form of adult-onset diabetes that can be difficult to diagnose due to its variable clinical phenotype. Transfer RNA-derived small fragments are a novel, emerging class of small non-coding RNAs (sncRNAs) that have significant potential as serum biomarkers due to their stress-induced generation, abundance, stability and ease of detection. METHODS: We investigated the levels of tiRNA 5'ValCAC (alone and in combination with miR-23b-3p) identified from small RNA sequencing studies in serum samples from healthy controls, type 1 diabetes, type 2 diabetes and MIDD subjects. RESULTS: Serum levels of 5'ValCAC were reduced in MIDD and type 2 diabetes subjects compared to controls. Type 2 diabetes subjects had higher serum levels of miR-23b-3p compared to all other subjects. Receiver Operating Characteristic analysis showed the potential of 5'ValCAC and miR-23b-3p as MIDD biomarkers, with the combination showing excellent separation from type 2 diabetes subjects. CONCLUSIONS: This is the first report showing altered serum levels of tiRNAs in diabetes subjects. The combined use of 5'ValCAC and miR-23b-3p as serum biomarkers could potentially differentiate between MIDD subjects and type 2 diabetes subjects.