Prediction of 24-Hour Urinary Sodium Excretion Using Machine-Learning Algorithms.

BACKGROUND: Accurate quantification of sodium intake based on self-reported dietary assessments has been a persistent challenge. We aimed to apply machine-learning (ML) algorithms to predict 24-hour urinary sodium excretion from self-reported questionnaire information. METHODS AND RESULTS: We analyzed 3454 participants from the NHS (Nurses' Health Study), NHS-II (Nurses' Health Study II), and HPFS (Health Professionals Follow-Up Study), with repeated measures of 24-hour urinary sodium excretion over 1 year. We used an ensemble approach to predict averaged 24-hour urinary sodium excretion using 36 characteristics. The TOHP-I (Trial of Hypertension Prevention I) was used for the external validation. The final ML algorithms were applied to 167 920 nonhypertensive adults with 30-year follow-up to estimate confounder-adjusted hazard ratio (HR) of incident hypertension for predicted sodium. Averaged 24-hour urinary sodium excretion was better predicted and calibrated with ML compared with the food frequency questionnaire (Spearman correlation coefficient, 0.51 [95% CI, 0.49-0.54] with ML; 0.19 [95% CI, 0.16-0.23] with the food frequency questionnaire; 0.46 [95% CI, 0.42-0.50] in the TOHP-I). However, the prediction heavily depended on body size, and the prediction of energy-adjusted 24-hour sodium excretion was modestly better using ML. ML-predicted sodium was modestly more strongly associated than food frequency questionnaire-based sodium in the NHS-II (HR comparing Q5 versus Q1, 1.48 [95% CI, 1.40-1.56] with ML; 1.04 [95% CI, 0.99-1.08] with the food frequency questionnaire), but no material differences were observed in the NHS or HPFS. CONCLUSIONS: The present ML algorithm improved prediction of participants' absolute 24-hour urinary sodium excretion. The present algorithms may be a generalizable approach for predicting absolute sodium intake but do not substantially reduce the bias stemming from measurement error in disease associations.

Type 2 diabetes metabolomics score and risk of progression to type 2 diabetes among women with a history of gestational diabetes mellitus.

BACKGROUND: Several metabolites are individually related to incident type 2 diabetes (T2D) risk. We prospectively evaluated a novel T2D-metabolite pattern with a risk of progression to T2D among high-risk women with a history of gestational diabetes mellitus (GDM). METHODS: The longitudinal Nurses' Health Study II cohort enroled 116,429 women in 1989 and collected blood samples from 1996 to 1999. We profiled plasma metabolites in 175 incident T2D cases and 175 age-matched controls, all with a history of GDM before the blood draw. We derived a metabolomics score from 21 metabolites previously associated with incident T2D in the published literature by scoring according to the participants' quintile (1-5 points) of each metabolite. We modelled the T2D metabolomics score categorically in quartiles and continuously per 1 standard deviation (SD) with the risk of incident T2D using conditional logistic regression models adjusting for body mass index at the blood draw, and other established T2D risk factors. RESULTS: The percentage of women progressing to T2D ranged from 10% in the bottom T2D metabolomics score quartile to 78% in the highest score quartile. Adjusting for established T2D risk factors, women in the highest quartile had more than a 20-fold greater diabetes risk than women in the lowest quartile (odds ratios [OR] = 23.1 [95% CI = 8.6, 62.1]; p for trend<0.001). The continuous T2D metabolomics score was strongly and positively associated with incident T2D (adjusted OR = 2.7 per SD [95% CI = 1.9, 3.7], p < 0.0001). CONCLUSIONS: A pattern of plasma metabolites among high-risk women is associated with a markedly elevated risk of progression to T2D later in life.

Machine-learning-based prediction of fractional flow reserve after percutaneous coronary intervention.

BACKGROUND AND AIMS: Post-percutaneous coronary intervention (PCI) fractional flow reserve (FFR) reflects residual atherosclerotic burden and is associated with future events. How much post-PCI FFR can be predicted based on baseline basic information and the clinical relevance have not been investigated. METHODS: We compiled a multicenter registry of patients undergoing pre- and post-PCI FFR. Machine-learning (ML) algorithms were designed to predict post-PCI FFR levels from baseline demographics, quantitative coronary angiography, and pre-PCI FFR. FFR deviation was defined as actual minus ML-predicted post-PCI FFR levels, and its association with incident target vessel failure (TVF) was evaluated. RESULTS: Median (IQR) pre- and post-PCI FFR values were 0.71 (0.61, 0.77) and 0.88 (0.84, 0.93), respectively. The Spearman correlation coefficient of the actual and predicted post-PCI FFR was 0.54 (95% CI: 0.52, 0.57). FFR deviation was non-linearly associated with incident TVF (HR [95% CI] with Q3 as reference: 1.65 [1.14, 2.39] in Q1, 1.42 [0.98, 2.08] in Q2, 0.81 [0.53, 1.26] in Q4, and 1.04 [0.69, 1.56] in Q5). A model with polynomial function of continuous FFR deviation indicated increasing TVF risk for FFR deviation ≤0 but plateau risk with FFR deviation >0. CONCLUSIONS: An ML-based algorithm using baseline data moderately predicted post-PCI FFR. The deviation of post-PCI FFR from the predicted value was associated with higher vessel-oriented event.

Sleeping Difficulties, Sleep Duration, and Risk of Hypertension in Women.

BACKGROUND: Rates of poor sleep and hypertension are alarming worldwide. In this study, we investigate the association between sleeping difficulties and sleep duration with hypertension risk in women. METHODS: Sixty-six thousand one hundred twenty-two participants of the Nurses' Health Study 2, who were free of hypertension at baseline (2001), were followed prospectively for 16 years and incident hypertension assessed every 2 years. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for hypertension incidence associated with sleeping difficulties and sleep duration. RESULTS: During follow-up, we documented 25 987 incident cases of hypertension. After controlling for demographic and lifestyle risk factors, compared with women who slept 7 to 8 hours, women with shorter sleep duration had a significantly higher risk of hypertension (≤5 hours: HR, 1.10 [95% CI, 1.05-1.16]; 6 hours: HR, 1.07 [95% CI, 1.03-1.10]), whereas the risk for women with longer sleep duration was not statistically significant (9 hours: HR, 1.03 [95% CI, 0.97-1.10]; >9 hours: HR, 1.08 [95% CI, 0.94-1.23]). Compared with women rarely having difficulty falling or staying asleep, women sometimes or usually having these sleep difficulties had significantly higher risk of developing hypertension (HR, 1.14 [95% CI, 1.11-1.17] and 1.28 [95% CI, 1.22-1.35]; Ptrend<0.001). Early morning awakening was not associated with hypertension risk (Ptrend=0.722). There was no effect modification by night work or chronotype. CONCLUSIONS: Difficulty falling or staying asleep and short sleep duration were associated with higher risk of hypertension among women in our study. Screening for poor sleep could be useful in identifying people at higher risk for hypertension.

Contribution of periodontal health in cardiovascular secondary prevention: Analyses on hospitalized patients in cardiology units.

AIM: To investigate the association between dental health and incident cardiovascular disease (CVD) in secondary prevention setting. MATERIALS AND METHODS: A total of 888 patients with known CVD hospitalized in the cardiology unit were prospectively enrolled. We assessed the association between missing teeth and three variables of periodontitis and major adverse cardiovascular events (MACE), defined as a composite of cardiac death, acute myocardial infarction, stroke and hospital re-admission for congestive heart failure. RESULTS: During a median (Q1, Q3) follow-up of 4.6 (1.4, 6.7) years, an additional missing tooth was associated with a 3% (95% confidence interval [CI]: 1%-5%) higher hazard of MACE (p = .004). Compared with patients with 0 to ≤4 missing teeth, periods free from MACE (95% CI) by 5 years of follow-up were, on average, shorter by 0.17 (-0.04 to 0.37) years, 0.26 (0.04-0.49) years and 0.59 (0.34-0.85) years in patients with 5 to ≤7, 8 to ≤13 and >13 missing teeth, respectively. No significant associations were observed between periodontal measures and MACE incidence. CONCLUSIONS: In hospitalized patients with existing CVD, the total number of missing teeth was associated with incident MACE.

Abnormal physiological findings after FFR-based revascularisation deferral are associated with worse prognosis in women.

The prognostic value of abnormal resting Pd/Pa and coronary flow reserve (CFR) after fractional flow reserve (FFR)-guided revascularisation deferral according to sex remains unknown. From the ILIAS Registry composed of 20 hospitals globally from 7 countries, patients with deferred lesions following FFR assessment (FFR > 0.8) were included. (NCT04485234) The primary clinical endpoint was target vessel failure (TVF) at 2-years follow-up. We included 1392 patients with 1759 vessels (n = 564 women, 31.9%). Although resting Pd/Pa was similar between the sexes (p = 0.116), women had lower CFR than men (2.5 [2.0-3.2] vs. 2.7 [2.1-3.5]; p = 0.004). During a 2-year follow-up period, TVF events occurred in 56 vessels (3.2%). The risk of 2-year TVF was significantly higher in women with low versus high resting Pd/Pa (HR: 9.79; p < 0.001), whereas this trend was not seen in men. (Sex: P-value for interaction = 0.022) Furthermore, resting Pd/Pa provided an incremental prognostic value for 2-year TVF over CFR assessment only in women. After FFR-based revascularisation deferral, low resting Pd/Pa is associated with higher risk of TVF in women, but not in men. The predictive value of Pd/Pa increases when stratified according to CFR values, with significantly high TVF rates in women in whom both indices are concordantly abnormal.Clinical Trial Registration: Inclusive Invasive Physiological Assessment in Angina Syndromes Registry (ILIAS Registry), NCT04485234.

Synthesized 18-Lead Electrocardiogram in Diagnosing Posterior Stemi-Equivalent Acute Coronary Syndrome in Patients with NSTEMI.

Objective: To assess the clinical utility of synthesized V7-V9 ST-segment elevation (sV7-9 STE) in patients with 12-lead-electrocardiogram (ECG)-based non-STE myocardial infarction (NSTEMI) in diagnosing left circumflex artery (LCx) STEMI-equivalent acute coronary syndrome (ACS). Background: The 12-lead-ECG is insufficient for diagnosing patients with ACS, especially those with an LCx culprit. Methods: We retrospectively examined 219 patients with NSTEMI who underwent synthesized 18-lead ECG acquisition on admission and urgent catheterization. Associations between baseline variables, including sV7-9 STE and LCx STEMI-equivalent ACS, were analyzed using logistic regression models and receiver operating characteristics. LCx-culprit ACS was defined as thrombolysis in myocardial infarction (TIMI) 0-1 flow. The association between sV7-9 STE and myocardial damage was also assessed. Results: The mean (SD) age of the population was 68.8 (12.0) years, and 81.7% were men. LCx-culprit NSTEMI occurred in 58 (26.5%) patients and 15 (6.8%) were LCx STEMI-equivalent. SV7-9 STE was observed in 16 patients (7.9%). SV7-9 STE was the sole significant predictor of LCx STEMI-equivalent ACS with an odds ratio of 19.0 (95% CI: 5.6-63.9, p < 0.001), area under the curve of 0.71 (95% CI: 0.58-0.84), sensitivity of 46.7%, and specificity of 95.6%. After adjustment for confounders, sV7-9 STE was significantly associated with a 308% (95% CI: 78-834%) increase in peak high-sensitivity cardiac troponin I (p=0.001). Conclusions: SV7-9 STE had sole preprocedural diagnostic utility in detecting LCx STEMI-equivalent ACS with greater myocardial damage among patients with 12 ECG-based NSTEMI. The use of synthesized extra leads on admission may help identify patients with NSTEMI requiring primary revascularization.

Association of Smartphone-Recorded Steps Over Years and Change in Cardiovascular Risk Factors Among Working-Age Adults.

Background Few data exist on long-term steps and their relation to changes in cardiovascular disease risk factors. We aimed to examine the associations using long-term smartphone-recorded steps. Methods and Results The present analysis made use of data from 2 national databases and a commercial app database. We evaluated the associations between smartphone-recorded daily steps over 2 years and 2-year changes in the cardiovascular disease risk factors. A total of 15 708 participants with mean (SD) age of 44.1 (9.5) and 23.5% women were included. After adjustment for potential confounders, differences in weight were almost linearly associated with 2-year steps in men (estimate [SE] per 1000 steps/d: -0.33 [0.029] kg), and inversely related only above 5000 steps/d in women (-0.18 [0.054] kg). An inverse linear association with systolic blood pressure was observed in men (-0.34 [0.097] mm Hg) but not in women. Greater steps were associated with change in high-density lipoprotein cholesterol and triglycerides (0.61 [0.068] and -3.4 [0.61] mg/dL in men; 0.64 [0.17] and -2.3 [0.67] mg/dL in women), while changes in low-density lipoprotein cholesterol were evident in men only (-0.59 [0.17] mg/dL). A significant negative association with hemoglobin A1c was observed only in women (-0.012 [0.0043] %). Conclusions In a large cohort of Japanese adults, smartphone-recorded steps over years were associated with beneficial changes in cardiovascular disease risk factors, with some differences between men and women in the associational patterns. The findings support the benefit of long-term physical activity for cardiovascular disease health and suggest a useful role of smartphone-recorded steps for monitoring cardiovascular disease risk over the long term.

Robust Association Between Changes in Coronary Flow Capacity Following Percutaneous Coronary Intervention and Vessel-Oriented Outcomes and the Implication for Clinical Practice.

Background: Coronary flow capacity (CFC) is a potentially important physiologic marker of ischemia for guiding percutaneous coronary intervention (PCI) indication, while the changes through PCI have not been investigated. Objectives: To assess the determinants and prognostic implication of delta CFC, defined as the change in the CFC status following PCI. Materials and Methods: From a single-center registry, a total of 450 patients with chronic coronary syndrome (CCS) who underwent fractional flow reserve (FFR)-guided PCI with pre-/post-PCI invasive coronary physiological assessments were included. Associations between PCI-related changes in thermodilution method-derived CFC categories and incident target vessel failure (TVF) were assessed. Results: The mean (SD) age was 67.1 (10.0) years and there were 75 (16.7%) women. Compared with patients showing no change in CFC categories after PCI, patients with category worsened, +1, +2, and +3 category improved had the hazard ratio (95% CI) for incident TVF of 2.27 (0.95, 5.43), 0.85 (0.33, 2.22), 0.45 (0.12, 1.63), and 0.14 (0.016, 1.30), respectively (p for linear trends = 0.0051). After adjustment for confounders, one additional change in CFC status was associated with 0.61 (0.45, 0.83) times the hazard of TVF. CFC changes were largely predicted by the pre-PCI CFC status. Conclusion: Coronary flow capacity changes following PCI, which was largely determined by the pre-PCI CFC status, were associated with the lower risk of incident TVF in patients with CCS who underwent PCI. The CFC changes provide a mechanistic explanation on potential favorable effect of PCI on reducing vessel-oriented outcome in lesions with reduced CFC and low FFR.

Differential Impact of Coronary Revascularization on Long-Term Clinical Outcome According to Coronary Flow Characteristics: Analysis of the International ILIAS Registry.

BACKGROUND: Coronary pressure indices such as fractional flow reserve are the standard for guiding elective revascularization. However, considering additional coronary flow parameters could further individualize and optimize the decision on revascularization. We aimed to investigate the potentially differential prognostic associations of elective percutaneous coronary intervention (PCI) according to coronary flow properties represented by coronary flow reserve (CFR), coronary flow capacity (CFC), and baseline CFC (bCFC). METHODS: From the ILIAS Registry (Inclusive Invasive Physiological Assessment in Angina Syndromes) composed of 16 hospitals globally from 7 countries, patients with obstructive coronary artery disease who underwent invasive coronary physiological assessment were included (N=2370 vessels). We assessed effect measure modifications of the association of PCI and 5-year target vessel failure according to CFR, CFC, and bCFC either assessed by Doppler-technique or thermodilution-method. RESULTS: The mean age of the population was 63.3 years, and there were 1322 (73.6%) males. Median fractional flow reserve was 0.85, and PCI was performed in 600 (25.3%) vessels. Reduced CFR, CFC, and abnormal bCFC were defined in 988 (41.7%), 542 (22.9%), and 600 (25.3%) vessels, respectively. Significant effect measure modifications were observed by CFC either in odds ratio (P=0.0018), additive (P=0.029), and hazard ratio scale (P=0.0002). The absolute risk of 5-year target-vessel failure was higher if treated by PCI in vessels with normal CFC by 1.8 (-1.7 to 5.3) percent, while that was lower by -5.9 (-12 to -0.1) percent in those with reduced CFC. CFR and bCFC were not significant effect modifiers in any scales. Similar associations were observed in per-patient analyses, whereas the findings were less robust. CONCLUSIONS: We observed qualitative effect measure modification of PCI and 5-year clinical outcomes according to CFC status in additive scale. CFR and bCFC were not robust effect modifiers. Therefore, CFC could be potentially used to optimize the patient selection for elective PCI treatment combined with fractional flow reserve.

The effect of diabetes on surgical versus percutaneous left main revascularization outcomes: a systematic review and meta-analysis.

BACKGROUND: The optimal method of coronary revascularization for diabetes mellitus (DM) patients with left main coronary artery disease (LMCAD) is controversial in the drug-eluting stent (DES) era. METHODS: We performed a systematic review and meta-analysis comparing DES-based percutaneous coronary intervention (PCI) to coronary artery bypass grafting (CABG) for LMCAD in DM patients and tested for effect measure modification (EMM) by diabetes for adverse events. We included all randomized controlled trials (RCTs) and observational studies comparing CABG to DES-based PCI including DM patients with LMCAD published up to March 1, 2021. We completed separate random-effects meta-analyses for four RCTs (4356 patients, mean follow-up of 4.9 years) and six observational studies (9360 patients, mean follow-up of 5.2 years). RESULTS: In RCTs among DM patients, DES-based PCI, compared to CABG, was associated with a 30% increased relative risk (RR) (RR 1.30, 95% CI 1.09-1.56, I2 = 0%), while among non-DM patients, there was a 25% increased relative risk (RR 1.25, 95% CI 1.07-1.44, I2 = 0%) for the composite endpoint of all-cause mortality, myocardial infarction, stroke, and unplanned revascularization (MACCE). There was no evidence of EMM (p-value for interaction = 0.70). The mean weighted SYNTAX score was 25.7. In observational studies, there was no difference between DES-based PCI and CABG for all-cause mortality in patients with DM (RR 1.13, 95% CI 0.91-1.40, I2 = 0%). CONCLUSIONS: CABG was superior to PCI for LMCAD in RCTs in DM patients for MACCE. Heart teams may consider DM as one of the many components in the clinical decision-making process, but may not want to consider DM as a primary deciding factor between DES-based PCI and CABG for LMCAD with low to intermediate anatomical complexity in the other coronary arteries. STUDY REGISTRATION: CRD42021246931 (PROSPERO).

Association of Modifiable Lifestyle Factors with Plasma Branched-Chain Amino Acid Metabolites in Women.

BACKGROUND: Circulating branched-chain amino acids (BCAAs-isoleucine, leucine, and valine) are strongly associated with higher risk of incident type 2 diabetes (T2D); however, determinants of elevated fasting BCAA concentrations are largely unknown. OBJECTIVES: We aimed to characterize the modifiable lifestyle factors related to plasma BCAAs. METHODS: We performed a cross-sectional analysis among n = 18,897 women (mean ± SD age: 54.9 ± 7.2 y) in the Women's Health Study, free of T2D and cardiovascular disease at baseline blood draw. Lifestyle factors, weight, and height were self-reported via questionnaire, including smoking status, alcohol, leisure-time physical activity (LTPA), diet quality scores [2010 Alternative Healthy Eating Index (without alcohol) (aHEI); alternate Mediterranean Diet (aMED)], and dietary sources of BCAAs. Plasma BCAAs were quantified via NMR spectroscopy. We calculated multivariable-adjusted percentage mean differences (95% CIs) and P values for linear trend of BCAAs stratified by categoric lifestyle factors. We estimated R2 from univariate cubic spline regression models to estimate the variability in BCAAs explained. RESULTS: Compared with women with BMI (in kg/m2) <25.0, BCAAs were 8.6% (95% CI: 8.0%, 9.3%), 15.3% (95% CI: 14.4%, 16.3%), and 21.0% (95% CI: 18.2%, 23.9%) higher for the BMI strata 25.0-29.9, 30.0-39.9, and ≥40.0, respectively (P-trend < 0.0001). Women with higher LTPA and higher alcohol intake compared with lower had modestly (∼1%) lower plasma BCAAs (P-trend = 0.014 and 0.0003, respectively). Differences in smoking status, aHEI, and aMED score were not related to plasma BCAAs. Women with higher dietary BCAAs had dose-response higher plasma BCAA concentrations, 3.4% (95% CI: 2.5%, 4.4%) higher when comparing the highest with the lowest quintile (P-trend < 0.0001). BMI explained 11.6% of the variability of BCAAs, whereas other factors explained between 0.1% and 1%. CONCLUSIONS: Our findings among a large cohort of US women indicate that BMI, but less so diet, physical activity, and other lifestyle factors, is related to plasma BCAAs.This trial was registered at clinicaltrials.gov as NCT00000479.

Preprocedural transthoracic Doppler echocardiography to identify stenosis associated with increased coronary flow after revascularisation.

The benefit of percutaneous coronary intervention (PCI) has been reported to be associated with functional stenosis severity defined by fractional flow reserve (FFR). This study aimed to investigate the predictive ability of preprocedural transthoracic Doppler echocardiography (TDE) for increased coronary flow. A total of 50 left anterior descending arteries (LAD) that underwent TDE examinations were analysed. Hyperaemic LAD diastolic peak velocity (hDPV) was used as a surrogate of volumetric coronary flow. The increase in coronary flow was evaluated by the metric of % hDPV-increase defined by 100× (post-PCI hDPV-pre-PCI hDPV)/pre-PCI hDPV. The two groups divided by the median value of % hDPV-increase were compared, and the determinants of a significant coronary flow increase defined as more than the median % hDPV-increase were explored. After PCI, FFR values improved in all cases. hDPV significantly increased from 53.0 to 76.0 mm/s (P < 0.01) and the median % hDPV-increase was 45%, while hDPV decreased in 10 patients. On multivariable analysis, pre-PCI FFR and hDPV were independent predictors of a significant coronary flow increase. Preprocedural TDE-derived hDPV provided significant improvement of identification of lesions that benefit from revascularisation with respect to significant coronary flow increase.

Prognostic Value of Coronary Sinus Flow Quantification by Cardiac Magnetic Resonance Imaging in Patients With Acute Myocardial Infarction.

Background This study aimed to evaluate the prognostic value of hyperemic coronary sinus flow (h-CSF) and global coronary flow reserve (g-CFR) obtained by phase-contrast cine-magnetic resonance imaging in patients with acute myocardial infarction (MI). Methods and Results This retrospective study analyzed patients with acute MI (n=523) who underwent primary (ST-segment-elevation MI) or urgent (non-ST-segment-elevation MI) percutaneous coronary intervention. Absolute coronary sinus blood flow (CSF) at rest and during vasodilator stress hyperemia was quantified at 30 days (24-36 days) after the index infarct-related lesion percutaneous coronary intervention and revascularization of functionally significant non-infarct-related lesions. We used Cox proportional hazards regression modeling to examine the association between h-CSF, g-CFR, and major adverse cardiac events defined as all-cause death, nonfatal MI, hospitalization for congestive heart failure, and stroke. Finally, 325 patients with ST-segment-elevation MI (62.1%) and 198 patients with non-ST-segment-elevation MI (37.9%) were studied over a median follow-up of 2.5 years. The rest CSF, h-CSF, and g-CFR were 0.94 (0.68-1.26) mL/min per g, 2.05 (1.42-2.73) mL/min per g, and 2.17 (1.54-3.03), respectively. Major adverse cardiac events occurred in 62 patients, and Cox proportional hazards analysis showed that h-CSF and g-CFR were independent predictors of major adverse cardiac events (h-CSF: hazard ratio [HR], 0.64; 95% CI, 0.47-0.88; P=0.005; g-CFR: HR, 0.62; 95% CI, 0.47-0.82; P=0.001). When stratified by h-CSF and g-CFR, cardiac event-free survival was the worst in patients with concordantly impaired h-CSF (<1.6 mL/min per g) and g-CFR (<1.7) (P<0.001). Conclusions Global coronary sinus flow quantification using phase-contrast cine-magnetic resonance imaging provided significant prognostic information independent of infarction size and conventional risk factors in patients with acute MI undergoing revascularization.

Association of near-infrared spectroscopy-defined lipid rich plaque with lesion morphology and peri-coronary inflammation on computed tomography angiography.

BACKGROUND AND AIMS: Recent studies have reported that the lipid-rich plaque (LRP) detected by near-infrared spectroscopy (NIRS) and the pericoronary adipose tissue attenuation (PCATA) evaluated by coronary computed tomography angiography (CCTA) are associated with worse outcomes. We sought to investigate the relationship between NIRS-defined LRP and PCATA or the incremental ability of PCATA for the prediction of the presence of NIRS-defined LRP when added to the CCTA-derived morphometric findings. METHODS: A total of 101 de novo lesions of 101 patients with chronic coronary syndromes (CCS), who underwent pre-procedural CCTA and NIRS during percutaneous coronary intervention (PCI), were retrospectively studied. PCATA was assessed by the crude analysis of the mean CT attenuation value of the culprit vessel. NIRS-defined LRP was defined as a maximum lipid core burden index in 4 mm ≥ 400. Univariate and multivariate logistic regression analyses were performed to determine the predictors of NIRS-defined LRP. RESULTS: NIRS-defined LRP was observed in 37 patients and median PCATA was -72.71. A significant relationship was observed between LCBI and PCATA (r = 0.24, p = 0.001). PCATA (OR: 4.99; 95% CI: 1.48-16.82; p = 0.010) and CCTA-derived positive remodeling (OR: 12.53; 95% CI: 3.56-44.07; p < 0.001) were independent predictors of NIRS-defined LRP. Net reclassification and integrated discrimination improvement indices were both significantly improved when PCATA was added to the reference model including clinical characteristics and CCTA-derived morphometric findings. CONCLUSIONS: Comprehensive assessment of CCTA including PCATA may provide reliable information to identify the presence of NIRS-defined LRP potentially leading to future adverse events after PCI.

Differential Prognostic Implications of Pre- and Post-Stent Fractional Flow Reserve in Patients Undergoing Percutaneous Coronary Intervention.

BACKGROUND AND OBJECTIVES: The influence of pre-intervention coronary physiologic status on outcomes post percutaneous coronary intervention (PCI) is not well known. We sought to investigate the prognostic implications of pre-PCI fractional flow reserve (FFR) combined with post-PCI FFR. METHODS: A total of 1,479 PCI patients with pre-and post-PCI FFR data were analyzed. The patients were classified according to the median values of pre-PCI FFR (0.71) and post-PCI FFR (0.88). The primary outcome was target vessel failure (TVF) at 2 years. RESULTS: The risk of TVF was higher in the low pre-PCI FFR group than in the high pre-PCI FFR group (hazard ratio, 1.82; 95% confidence interval, 1.15-2.87; p=0.011). In 4 group comparisons, the cumulative incidences of TVF at 2 years were 3.8%, 4.1%, 4.8%, and 10.2% in the high pre-/high post-, low pre-/high post-, high pre-/low post-, and low pre-/low post-PCI FFR groups, respectively. The risk of TVF was the highest in the low pre-/low post-PCI FFR group among the groups (p values for comparisons <0.05). In addition, the high pre-/low post-PCI FFR group presented a comparable risk of TVF with the high post-PCI FFR groups (p values for comparison >0.05). When the prognostic value of the post-PCI FFR was evaluated according to the pre-PCI FFR, the risk of TVF significantly decreased with an increase in post-PCI FFR in the low pre-PCI FFR group, but not in the high pre-PCI FFR group. CONCLUSIONS: Pre-PCI FFR was associated with clinical outcomes after PCI, and the prognostic value of post-PCI FFR differed according to the pre-PCI FFR. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04012281.

Effect of Coronary Disease Characteristics on Prognostic Relevance of Residual Ischemia After Stent Implantation.

Objectives: We investigated the influence of coronary disease characteristics on prognostic implications of residual ischemia after coronary stent implantation. Methods: This study included 1,476 patients with drug-eluting stent implantation and available pre- and post-percutaneous coronary intervention (PCI) fractional flow reserve (FFR) measurements. Residual ischemia was defined as post-PCI FFR ≤ 0.80. Coronary disease characteristics with significant interaction hazard ratios (HRs) for clinical outcomes with residual ischemia were defined as interaction characteristics with residual ischemia (ICwRI). The primary outcome was target vessel failure (TVF)-a composite of cardiac death, target vessel myocardial infarction, and target vessel revascularization-at 2 years. Results: The mean pre- and post-PCI FFR were 0.68 ± 0.11 and 0.87 ± 0.07, respectively. During the median follow-up duration of 2.0 years, the cumulative incidence of TVF was 6.1%. The 203 vessels (13.8%) with residual ischemia had higher risks of TVF compared to that for post-PCI FFR >0.80 (P < 0.001). ICwRI with a significant interaction HR with residual ischemia included pre-PCI SYNTAX score >17 and pre-PCI FFR ≤ 0.62. Each ICwRI had a direct prognostic effect not mediated by residual ischemia. The association between an increased TVF risk and residual ischemia was significant in patients with 0 or 1 ICwRI [hazard ratio (HR) 3.25, 95% confidence interval (CI) 1.90-5.57, P < 0.001] but not in those with 2 ICwRI (HR 0.47, 95% CI 0.14-1.64, P = 0.24). Among patients with post-PCI FFR >0.80, those with 2 ICwRI showed similar TVF risks to those with residual ischemia (HR 1.55, 95% CI 0.79-3.02, P = 0.20). Conclusions: Coronary disease characteristics including pre-PCI SYNTAX score and pre-PCI FFR affected the prognostic implications of residual ischemia. The prognostic relevance of residual ischemia was attenuated in patients with multiple interacting characteristics.

Physiological significance of pericoronary inflammation in epicardial functional stenosis and global coronary flow reserve.

Both fractional flow reserve (FFR) and global coronary flow reserve (g-CFR) provide prognostic information in patients with stable coronary artery disease (CAD). Inflammation plays a vital role in impaired endothelial dysfunction and atherosclerotic progression, potentially predicting cardiovascular mortality. This study aimed to evaluate the physiological significance of pericoronary adipose tissue inflammation assessed by CT attenuation (PCATA) in epicardial functional stenosis severity and g-CFR in patients with CAD. A total of 131 CAD patients with a single de novo epicardial coronary stenosis who underwent coronary CT-angiography (CCTA), phase-contrast cine-magnetic resonance imaging (PC-CMR) and FFR measurement were studied. PCATA was assessed using the mean CT attenuation value. G-CFR was obtained by quantifying absolute coronary sinus flow (ml/min/g) by PC-CMR at rest and during maximum hyperemia. Median FFR, g-CFR, and PCATA values were 0.75, 2.59, and - 71.3, respectively. Serum creatinine, NT-proBNP, left ventricular end-diastolic volume, and PCATA were independently associated with g-CFR. PCATA showed a significant incremental predictive efficacy for impaired g-CFR (< 2.0) when added to the clinical risk model. PCATA was significantly associated with g-CFR, independent of FFR. Our results suggest the pathophysiological mechanisms linking perivascular inflammation with g-CFR in CAD patients.