Abstract Objectives This study investigated the role of fractional myocardial mass (FMM), a vessel-specific myocardial mass, in the evaluation of physiological severity of stenosis. Using computed ...tomography angiography, the study investigated fractional myocardial mass, a concept of myocardial mass subtended by specific vessel, which could reduce anatomical-physiological mismatch. Background Discordance between anatomical stenosis and physiological severity is common but remains poorly understood. Methods This multicenter study enrolled 463 patients with 724 lesions, who underwent coronary computed tomography angiography (CCTA) and invasive coronary angiography with fractional flow reserve (FFR) measurement. FMM was assessed by allometric scaling analysis of arterial tree length and myocardial mass from CCTA. Results FFR <0.80, a criteria for vessel-specific physiological stenosis, was found in 281 vessels (39%). FMM decreased consistently according to the vessel downstream (p < 0.001, all). The frequency of FFR <0.80 increased in proportion to FMM and inverse proportion to angiographic minimal luminal diameter (MLD) (p < 0.001). In per-vessel analysis, FMM per MLD (FMM/MLD) showed good correlation with FFR (r = 0.61) and was superior to diameter stenosis (DS) for FFR <0.80 by receiver operating characteristic and reclassification analysis (C-statistics = 0.84 versus 0.74, net reclassification improvement NRI = 0.63, integrated discrimination improvement IDI = 0.18; p < 0.001, all). The optimal cutoff of FMM/MLD was 29 g/mm, with sensitivity = 75%, specificity = 77%, positive predictive value = 68%, negative predictive value = 83%, and accuracy = 77%. Addition of FMM/MLD to DS could further discriminate vessels with FFR <0.80 (C-statistic = 0.86 vs. 0.84, NRI = 0.34, IDI = 0.03; p < 0.005, all). In per-range classification analysis, agreement between FFR and FMM/MLD maintained >80% when the severity of disease was away from cutoff. Conclusions FMM/MLD could find physiological severity of coronary artery with higher accuracy than anatomical stenosis. FMM may explain the anatomical-physiological discordance.
Background Soluble inflammatory mediators are known to exacerbate sepsis-induced acute kidney injury (AKI). Continuous renal replacement therapy (CRRT) has been suggested to play a part in ...immunomodulation by cytokine removal. However, the effect of continuous venovenous hemodiafiltration (CVVHDF) dose on inflammatory cytokine removal and its influence on patient outcomes are not yet clear. Study Design Prospective, randomized, controlled, open-label trial. Setting & Participants Septic patients with AKI receiving CVVHDF for AKI. Intervention Conventional (40 mL/kg/h) and high (80 mL/kg/h) doses of CVVHDF for the duration of CRRT. Outcomes Patient and kidney survival at 28 and 90 days, circulating cytokine levels. Results 212 patients were randomly assigned into 2 groups. Mean age was 62.1 years, and 138 (65.1%) were men. Mean intervention durations were 5.4 and 6.2 days for the conventional- and high-dose groups, respectively. There were no differences in 28-day mortality (HR, 1.02; 95% CI, 0.73-1.43; P = 0.9) or 28-day kidney survival (HR, 0.96; 95% CI, 0.48-1.93; P = 0.9) between groups. High-dose CVVHDF, but not the conventional dose, significantly reduced interleukin 6 (IL-6), IL-8, IL-1b, and IL-10 levels. There were no differences in the development of electrolyte disturbances between the conventional- and high-dose groups. Limitations Small sample size. Only the predilution CVVHDF method was used and initiation criteria were not controlled. Conclusions High CVVHDF dose did not improve patient outcomes despite its significant influence on inflammatory cytokine removal. CRRT-induced immunomodulation may not be sufficient to influence clinical end points.
Abstract Objectives The authors sought to identify whether a coronary side branch (SB) is supplying a myocardial mass that may benefit from revascularization. Background The amount of subtending ...myocardium and physiological stenosis is frequently different between the main vessel (MV) and SB. Methods In this multicenter registry, 482 patients who underwent coronary computed tomography angiography and fractional flow reserve (FFR) measurement were enrolled. The % fractional myocardial mass (FMM), the ratio of vessel-specific myocardial mass to whole myocardium, was assessed in 5,860 MV or SB consisting of 2,930 bifurcations. Physiological stenosis was defined by fractional flow reserve (FFR) <0.80. Myocardial mass that may benefit from revascularization was defined by %FMM ≥10%. Results In per-bifurcation analysis, MV supplied a 1.5- to 9-fold larger myocardial mass compared with SB. Unlike left main bifurcation (n = 482), only 1 of every 5 non-left main SB (n = 2,448) supplied %FMM ≥10% (97% vs. 21%; p < 0.001). SB length ≥73 mm could estimate %FMM ≥10% (c-statistic = 0.85; p < 0.001). In 604 vessels interrogated by FFR, diameter stenosis was similar (p = NS), but %FMM ≥10%, FMM/minimal luminal diameter, and frequency of FFR <0.80 was higher in MV compared with SB (p < 0.001, all). Generalized estimating equations modeling demonstrate that vessel diameter, left myocardial mass, and FFR were not (p = NS), but SB length ≥73 mm and left main bifurcation were significant predictors for %FMM ≥10% (p < 0.001). Conclusions Compared with MV, SB supplies a smaller myocardial mass and showed less physiological severity despite similar stenosis severity. SB supplying a myocardial mass of %FMM≥10%, which may benefit revascularization could be identified by vessel length ≥73 mm. Pre-procedural recognition of these findings may guide optimal revascularization strategy for bifurcation.
Abstract Background The prognostic impact of microvascular status in patients with high fractional flow reserve (FFR) is not clear. Objectives The goal of this study was to investigate the ...implications of coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR) in patients who underwent FFR measurement. Methods Patients with high FFR (>0.80) were grouped according to CFR (≤2) and IMR (≥23 U) levels: group A, high CFR with low IMR; group B, high CFR with high IMR; group C, low CFR with low IMR; and group D, low CFR with high IMR. Patient-oriented composite outcome (POCO) of any death, myocardial infarction, and revascularization was assessed. The median follow-up was 658 days (interquartile range: 503.8 to 1,139.3 days). Results A total of 313 patients (663 vessels) were assessed with FFR, CFR, and IMR. Correlation ( r = 0.201; p < 0.001) and categorical agreement (kappa value = 0.178; p < 0.001) between FFR and CFR were modest. Low CFR was associated with higher POCO than high CFR (p = 0.034). There were no significant differences in clinical and angiographic characteristics among groups. Patients with high IMR with low CFR had the highest POCO (p = 0.002). Overt microvascular disease (p = 0.008), multivessel disease (p = 0.033), and diabetes mellitus (p = 0.033) were independent predictors of POCO. Inclusion of a physiological index significantly improved the discriminant function of a predictive model (relative integrated discrimination improvement 0.467 p = 0.037; category-free net reclassification index 0.648 p = 0.007). Conclusions CFR and IMR improved the risk stratification of patients with high FFR. Low CFR with high IMR was associated with poor prognosis. (Clinical, Physiological and Prognostic Implication of Microvascular Status; NCT02186093 )
Abstract Objectives This study sought to investigate the impact of longitudinal lesion geometry on the location of plaque rupture and clinical presentation and its mechanism. Background The ...relationships among lesion geometry, external hemodynamic forces acting on the plaque, location of plaque rupture, and clinical presentation have not been comprehensively investigated. Methods This study enrolled 125 patients with plaque rupture documented by intravascular ultrasound. Longitudinal locations of plaque rupture were identified and categorized by intravascular ultrasound. Patients’ clinical presentations and TIMI (Thrombolysis In Myocardial Infarction) flow grade in an initial angiogram were compared according to the location of plaque rupture. Longitudinal lesion asymmetry was quantitatively assessed by the luminal radius change over the segment length (radius gradient RG). Lesions with a steeper radius change in the upstream segment compared with the downstream segment (RGupstream > RGdownstream ) were defined as upstream-dominant lesions. Results On the basis of the site of maximum rupture aperture, 56.0%, 16.0%, and 28.0% of the patients had upstream, minimal lumen area, and downstream rupture, respectively. Patients with upstream rupture more frequently presented with ST-segment elevation myocardial infarction (45.7%, 40.0%, 22.9%; p = 0.030) and with TIMI flow grade <3 (32.9%, 20.0%, 17.1%; p = 0.042). According to the ratio of upstream and downstream RG, 69.5% of lesions were classified as upstream-dominant lesions, and 30.5% were classified as downstream-dominant lesions. Among the 66 upstream-dominant lesions, 65 cases (98.5%) had upstream rupture, and the RG ratio (RGupstream /RGdownstream ) was an independent predictor of upstream rupture (odds ratio: 1.481; 95% confidence interval: 1.035 to 2.120; p = 0.032). Upstream-dominant lesions more frequently manifested with ST-segment elevation myocardial infarction than did downstream-dominant lesions (48.5% vs. 24.1%; p = 0.026). Conclusions Both clinical presentation and degree of flow limitation were associated with the location of plaque rupture. Longitudinal lesion asymmetry assessed by RG, which can affect regional distribution of hemodynamic stress, was associated with the location of rupture and with clinical presentation.
Objectives This study sought to compare everolimus-eluting stents (EES) versus Resolute zotarolimus-eluting stents (ZES) in terms of patient- or stent-related clinical outcomes in an “all-comer” ...group of patients with diabetes mellitus (DM) who underwent percutaneous coronary intervention. Background DM significantly increases the risk of adverse events after percutaneous coronary intervention. The efficacy and safety of second-generation drug-eluting stents, in particular EES versus ZES, in patients with DM have not been extensively evaluated. Methods Patients with DM (1,855 of 5,054 patients, 36.7%) from 2 prospective registries (the EXCELLENT Efficacy of Xience/Promus Versus Cypher in Reducing Late Loss After Stenting registry and RESOLUTE-Korea Registry to Evaluate the Efficacy of Zotarolimus-Eluting Stent) who were treated with EES (n = 1,149) or ZES (n = 706) were compared. Stent-related outcome was target lesion failure (TLF), and patient-oriented composite events were a composite of all-cause mortality, any myocardial infarction, and any revascularization. Results Despite a higher risk patient profile in the ZES group, both TLF (43 of 1,149 3.7% vs. 25 of 706 3.5%, p = 0.899) and patient-oriented composite events (104 of 1,149 9.1% vs. 72 of 706 10.2%, p = 0.416) were similar between the EES and ZES in patients with DM at 1 year. In those without DM, EES and ZES also showed comparable incidence of TLF (39 of 1,882 2.1% vs. 33 of 1,292 2.6%, p = 0.370) and patient-oriented composite events (119 of 1,882 6.3% vs. 81 of 1,292 6.3%, p = 0.951), which were all significantly lower than in the DM patients. These results were corroborated by similar findings from the propensity score-matched cohort. Upon multivariate analysis, chronic renal failure was the most powerful predictor of TLF in DM patients (hazard ratio: 4.39, 95% confidence interval: 1.91 to 10.09, p < 0.001). Conclusions After unrestricted use of second-generation drug-eluting stents in all-comers receiving percutaneous coronary intervention, both EES and ZES showed comparable clinical outcomes in the patients with DM up to 1 year of follow-up. DM compared with non-DM patients showed significantly worse patient- and stent-related outcomes. Nonetheless, overall incidences of TLF were low, even in the patients with DM, suggesting excellent safety and efficacy of both types of second-generation drug-eluting stents in this high-risk subgroup of patients.
The prognostic value of whole vessel plaque quantification has not been fully understood.
We aimed to investigate the clinical relevance of whole vessel plaque quantification on coronary computed ...tomography angiography.
In a total of 1,013 vessels with fractional flow reserve (FFR) measurement and available coronary computed tomography angiography, high-risk plaque characteristics (HRPC) included minimum lumen area <4 mm2, plaque burden ≥70%, low attenuation plaque, positive remodeling, spotty calcification, and napkin-ring sign; and high-risk vessel characteristics (HRVC) included total plaque volume ≥306.5 mm3, fibrofatty and necrotic core volume ≥4.46 mm3, or percent total atheroma volume ≥32.2% in a target vessel, based on corresponding optimal cutoff values. Survival analysis for vessel-oriented composite outcome (VOCO) (a composite of cardiac death, target vessel myocardial infarction, or target vessel revascularization) at 5 years was performed using marginal Cox proportional hazard models.
Whole vessel plaque quantification had incremental predictability in addition to % diameter stenosis and HRPC (P < 0.001) in predicting FFR ≤0.80. Among 517 deferred vessels based on FFR >0.80, the number of HRVC was significantly associated with the risk of VOCO (HR: 2.54; 95% CI: 1.77-3.64) and enhanced the predictability for VOCO of % diameter stenosis and the number of HRPC (P < 0.001). In a landmark analysis at 2 years, the number of HRVC showed sustained prognostic implications beyond 2 years, but the number of HRPC did not.
Whole vessel plaque quantification can provide incremental predictability for low FFR and additive prognostic value in deferred vessels with high FFR over anatomical severity and lesion plaque characteristics. (CCTA-FFR Registry for Risk Prediction; NCT04037163)
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Background High serum phosphorus levels are associated with cardiovascular morbidity and mortality in kidney disease. Although serum phosphorus levels possibly influence on mortality in individuals ...without kidney disease, this is uncertain because of the variable sex- and age-based distribution of serum phosphorus levels. Study Design Observational cohort study. Setting & Participants Clinical and biochemical data were collected from 138,735 adults undergoing routine health checkups in 3 tertiary hospitals. Individuals with estimated glomerular filtration rates < 60 mL/min/1.73 m2 and urine dipstick albumin ≥ 1+ were excluded. Predictor Sex-specific quartiles of serum phosphorus and sex. Outcomes All-cause mortality. Results The study included 92,756 individuals. Generally, women showed higher serum phosphorus levels than men. In women, serum phosphorus levels increased with age until 60 years old, then decreased with age. Men with higher serum phosphorus levels were younger and less likely to have hypertension, whereas women with higher serum phosphorus levels were older and more likely to have diabetes and hypertension. During a median follow-up of 75 months, 1,646 participants died. In the overall population, higher serum phosphorus levels were an independent predictor for all-cause mortality after adjustment (adjusted HR for the highest vs lowest quartile, 1.34; 95% CI, 1.15-1.56; P < 0.001). We observed that this increased risk was present in men but not in women (adjusted HR of 1.43 95% CI, 1.22-1.68 vs 1.01 95% CI, 0.76-1.33), but interaction by sex was not significant ( P = 0.8). Limitations A single phosphorus measurement and low power to test for interactions by sex and age. Conclusions We demonstrated that higher serum phosphorus levels influenced all-cause mortality in individuals with normal kidney function. Our findings suggest that the association may differ by sex, but future studies with adequate power to test for effect modification are needed to confirm our findings.
Background Although there has been considerable investigation of the general characteristics of contrast-induced nephropathy (CIN), it has not been studied adequately in a computed tomography (CT) ...population. We assessed the incidence and outcomes of CIN after contrast-enhanced CT in patients with chronic kidney disease pretreated with saline and N -acetylcysteine (NAC). Design Quality improvement report. Setting & Participants 520 patients registered in a CIN prevention program. Quality Improvement Plan We initiated the CIN prevention program in January 2007. In this program, patients with chronic kidney disease undergoing contrast-enhanced CT in an outpatient setting were automatically referred to nephrologists, and patients received saline and NAC before and after CT. The development of CIN was assessed 48-96 hours after CT. Outcomes Incidence of CIN and time to renal replacement therapy. Measurements Baseline serum creatinine, hemoglobin, and serum albumin levels; type and volume of contrast agents; and post-CT serum creatinine level. Results Overall, CIN occurred in 13 (2.5%) patients. Incidences of CIN were 0.0%, 2.9%, and 12.1% in patients with an estimated glomerular filtration rate of 45-59, 30-44, and <30 mL/min/1.73 m2 , respectively. The risk of CIN was increased in patients with severely decreased kidney function and diabetes. The development of CIN consequently increased the risk of renal replacement therapy ( P < 0.001 by log-rank), and the risk was significantly accentuated in patients with estimated glomerular filtration rate <30 mL/min/1.73 m2. Limitations A single-center study and comparison with previous studies. Conclusions The incidence of CIN was relatively low in patients treated with saline and NAC. The development of CIN predisposed to poor kidney survival in the long term.
Summary Pathologic features can provide valuable information for determining prognosis in IgA nephropathy (IgAN). However, it is uncertain whether the Oxford classification, a new classification of ...IgAN, can predict renal outcome better than previous ones. We conducted a retrospective cohort study in 500 patients with biopsy-proven IgAN between January 2002 and December 2010 to compare the ability of the Haas and the Oxford classifications to predict renal outcome. Primary outcome was a doubling of the baseline serum creatinine concentration (D-SCr). During a mean follow-up of 68 months, 52 (10.4%) and 35 (7.0%) developed D-SCr and end-stage renal disease, respectively. There were graded increases in the development of D-SCr in the higher Haas classes. In addition, the primary endpoint of D-SCr occurred more in patients with the Oxford M and T lesions than those without such lesions. In multivariate Cox regression analyses, the Haas class V (HR, 12.19; P = .002) and the Oxford T1 (hazard ratio HR, 6.68; P < .001) and T2 (HR, 12.16; P < .001) lesions were independently associated with an increased risk of reaching D-SCr. Harrell’s C index of each multivariate model with the Haas and the Oxford classification was 0.867 ( P = .015) and 0.881 ( P = .004), respectively. This was significantly higher than that of model with clinical factors only ( C = 0.819). However, there was no difference in C -statistics between the 2 models with the Haas and the Oxford classifications ( P = .348). This study suggests that the Haas and the Oxford classifications are comparable in predicting progression of IgAN.
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