Clinical Outcomes Based on High Bleeding Risk in Patients With Lower Extremity Peripheral Artery Disease Who Have Undergone Endovascular Therapy.

PURPOSE: Endovascular therapies (EVTs) for symptomatic lower extremity peripheral artery disease (PAD) are efficient and minimally invasive. However, patients with PAD tend to have high bleeding risk (HBR), and there are limited data regarding the HBR for patients with PAD after EVT. In this study, we investigated the prevalence and severity of HBR, as well as its association with clinical outcomes in the patients with PAD who underwent EVT. MATERIALS AND METHODS: The Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria were applied to 732 consecutive patients with lower extremity PAD post-EVT to assess the prevalence of HBR, and its association with major bleeding events, all-cause mortality, and ischemic events. The ARC-HBR scores (1 point for each major criterion and 0.5 points for each minor criterion) were obtained and the patients were divided into four groups (score: 0-0.5; low risk, score: 1-1.5; moderate risk, score: 2-2.5; high risk, and score: ≥3; very high risk) according to the score. Major bleeding events were defined as Bleeding Academic Research Consortium type-3 or type-5 bleeding, and ischemic events were defined as the composite of myocardial infarction, ischemic stroke, and acute limb ischemia within 2 years. RESULTS: High bleeding risk occurred in 78.8% of the patients. Major bleeding events, all-cause mortality, and ischemic events occurred in 9.7%, 18.7%, and 6.4% of the study cohort, respectively, within 2 years. During the follow-up period, major bleeding events significantly increased with the ARC-HBR score. The severity of the ARC-HBR score was significantly associated with an increased risk of major bleeding events (high risk: adjusted hazard ratio [HR] 5.62; 95% confidence interval [CI]: [1.28, 24.62]; p=0.022; very high risk: adjusted HR: 10.37; 95% CI: [2.32, 46.30]; p=0.002). All-cause mortality and ischemic events also significantly increased with higher ARC-HBR score. CONCLUSIONS: High bleeding risk patients with lower extremity PAD can be at a high risk of bleeding events, mortality, and ischemic events after EVT. The ARC-HBR criteria and its associated scores can successfully stratify HBR patients and assess the bleeding risk in patients with lower extremity PAD who undergo EVT. CLINICAL IMPACT: Endovascular therapies (EVTs) for symptomatic lower extremity peripheral artery disease (PAD) are efficient and minimally invasive. However, patients with PAD tend to have high bleeding risk (HBR), and there are limited data regarding the HBR for patients with PAD after EVT. Post EVT, most of the patients with PAD were classified as having HBR using the Academic Research Consortium for HBR (ARC-HBR) criteria and the rate of bleeding events as well as mortality and ischemic events within 2 years increased as the ARC-HBR score increased in this retrospective study of 732 participants. HBR patients with PAD can be at high risk of not only bleeding events but also mortality and ischemic events in the mid-term. The ARC-HBR criteria and its associated scores can successfully stratify HBR patients and assess the bleeding risk in patients with PAD who underwent EVT.

Comparison of the OPTIVUS-Complex PCI Multivessel Cohort With the Historical CREDO-Kyoto Registry Cohort-3.

BACKGROUND: There is a paucity of data on the effect of optimal intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) compared with standard PCI or coronary artery bypass grafting (CABG) in patients with multivessel disease.Methods and Results: The OPTIVUS-Complex PCI study multivessel cohort was a prospective multicenter single-arm study enrolling 1,021 patients undergoing multivessel PCI including the left anterior descending coronary artery using IVUS aiming to meet the prespecified criteria for optimal stent expansion. We conducted propensity score matching analyses between the OPTIVUS group and historical PCI or CABG control groups from the CREDO-Kyoto registry cohort-3 (1,565 and 899 patients) fulfilling the inclusion criteria for this study. The primary endpoint was a composite of death, myocardial infarction, stroke, or any coronary revascularization. In the propensity score-matched cohort (OPTIVUS vs. historical PCI control: 926 patients in each group; OPTIVUS vs. historical CABG control: 436 patients in each group), the cumulative 1-year incidence of the primary endpoint was significantly lower in the OPTIVUS group than in the historical PCI control group (10.4% vs. 23.3%; log-rank P<0.001) or the historical CABG control group (11.8% vs. 16.5%; log-rank P=0.02). CONCLUSIONS: IVUS-guided PCI targeting the OPTIVUS criteria combined with contemporary clinical practice was associated with superior clinical outcomes at 1 year compared with not only the historical PCI control, but also the historical CABG control.

Two-year clinical outcomes and predictors of restenosis following the use of polymer-coated paclitaxel-eluting stents or drug-coated balloons in patients with femoropopliteal artery disease.

We aimed to assess the clinical performance and risk factors for patency loss within 2 years following the use of polymer-coated paclitaxel-eluting stents (PC-PESs) and drug-coated balloons (DCBs) in patients with lower extremity artery disease. Multi-center registry data from 151 patients (65 and 86 treated with PC-PES and DCB, respectively) were retrospectively investigated. Two-year primary patency (PP) and clinically driven target lesion revascularization (CD-TLR) were evaluated using Kaplan-Meier analysis. Predictors of restenosis within 2 years of the procedures were analyzed using the random survival forest method. The consistent predictors of restenosis within 1 and 2 years were assessed and validated using Kaplan-Meier analysis. Two-year PP was 77.2 and 57.2% (log rank p = 0.047) and freedom from CD-TLR was 84.4 and 84.8% in the PC-PES and DCB groups, respectively (log rank p = 0.89). In the DCB group, most of the patients (n = 77, 89.5%) were treated with high-dose DCB. Consistent predictors of restenosis were lower vessel diameter and severity of Clinical Frailty Scale in the PC-PES group, and severity of peripheral artery calcification scoring system grade, severity of post dissection pattern, and smaller vessel diameter in the DCB group. The validation analysis revealed that patients with consistent predictors had significantly worse PP values than that of those without in the PC-PES (87.9% vs. 55.3%, log rank p = 0.003) and DCB groups (75.9% vs. 35.2%, log rank p = 0.001). The 2-year PP of DCBs was lower than that of PC-PESs. A smaller vessel diameter could predict restenosis in both devices. Vessel calcification and dissection should be considered when using DCB to ensure longer term patency.

Clinical outcomes and predictors of restenosis in patients with femoropopliteal artery disease treated using polymer-coated paclitaxel-eluting stents or drug-coated balloons.

Both polymer-coated paclitaxel-eluting stents (PC-PESs) and drug-coated balloons (DCBs) are used in conjunction with endovascular therapy (EVT) for the treatment of peripheral artery disease (PAD). We aimed to identify the risk factors for the loss of patency following the use of PC-PES and DCB in a real clinical setting. We assessed the multi-center registry data of 151 lesions from 151 patients who underwent EVT for symptomatic PAD in the superficial femoral and proximal popliteal arteries using PC-PES or DCB. One-year primary patency (PP) and clinically driven target lesion revascularization (CD-TLR) were evaluated using Kaplan-Meier analysis. The predictive risk factors for 1-year outcomes were analyzed using the random survival forest method. PC-PES and DCB were used in 65 (43.0%) and 86 (57.0%) cases, respectively. There were no significant differences in 1-year PP or freedom from CD-TLR between PC-PES and DCB. PP occurred in 85.4% and 80.2% of cases in the PC-PES and DCB groups, respectively (log-rank p = 0.65), while freedom from CD-TLR was noted in 92.7% and 94.1% of cases in the PC-PES and DCB groups, respectively (log-rank p = 0.73). In order of importance, a Clinical Frailty Scale score ≥ 6, female sex, lower proximal vessel diameter, lower body mass index, and younger and older age were identified as predictive risk factors of restenosis in the PC-PES group. Peripheral artery calcification scoring system grade of ≥ 2, post-dissection pattern ≥ D, lower proximal and distal vessel diameter, and lesion length ≥ 100 mm were identified as predictive risk factors of restenosis, in order of importance, in the DCB group. Both PC-PES and DCB were associated with favorable clinical outcomes within 1 year in patients with femoropopliteal artery disease. Furthermore, several factors that could predict restenosis within 1 year following the use of each device were detected.

Chronic Limb-Threatening Ischemia is a Residual Bleeding Risk Factor among Patients with Lower Extremity Artery Disease.

AIM: Lower-extremity artery disease (LEAD) is a high-risk factor for bleeding. However, the specific risk factors for bleeding in patients with LEAD remain unclear. We aimed to identify risk factors for bleeding in patients with LEAD after endovascular treatment (EVT). METHODS: This multicenter, retrospective, observational study included 732 consecutive patients with LEAD who underwent EVT between January 2018 and December 2019. Patient characteristics, laboratory data, target lesions, and medications were compared between patients with and without chronic limb-threatening ischemia (CLTI). Predictive bleeding risk factors were explored using Cox regression analysis with differential models. RESULTS: In model 1, a body mass index (BMI) ＜18.5 kg/m2, prior heart failure, high bleeding risk, use of single antiplatelet therapy (SAPT) plus warfarin, and CLTI were predictive bleeding risk factors (hazard ratio [HR] 2.05; 95% confidence interval [CI] 1.13-3.52; p＜0.01; HR 2.15; 95% CI 1.28-3.55; p＜0.01; HR 3.40; 95% CI 1.28-3.55; p＜0.01; HR 2.05; 95% CI 1.33-5.84; p＜0.01; respectively). In model 2, a BMI ＜18.5 kg/m2, prior heart failure, anemia (＜11 g/dL), low platelet count (＜10*104/µL), chronic kidney disease, use of single antiplatelet therapy (SAPT) plus warfarin, and CLTI were independent risk factors for bleeding (model 2: HR 2.05; 95% CI 1.12-3.56; p=0.02; HR 2.35; 95% CI 1.39-3.90; p＜0.01; HR 2.71; 95% CI 1.64-4.50; p＜0.01; HR 2.66; 95% CI 1.00-5.89; p=0.05; HR 2.47; 95% CI 1.25-5.45; p＜0.01; HR 2.79; 95% CI 1.24-5.63; p=0.01; respectively) Conclusions: CLTI is a residual and predictive risk factor for bleeding in patients with LEAD. We have to pay attention to the bleeding events of patients with CLTI after EVT during follow-up.

Validation of the Usefulness of the Diameter Reduction, Spiral Shape, Flow Impairment, or Adverse Morphology Classification System in Real-World Clinical Practice.

AIM: The accuracy of the DISFORM (diameter reduction, spiral shape, flow impairment, or adverse morphology) classification system has not been validated. METHODS: This retrospective multicenter observational study enrolled 288 consecutive patients with lower extremity artery disease who underwent endovascular therapy with drug-coated balloons for femoropopliteal lesions between January 2018 and December 2021. Patients were classified into DISFORM I-IV groups. Primary patency (PP) and freedom from clinically driven target lesion revascularization (CD-TLR) at 12 months, and recurrence predictors at 12 months were investigated. RESULTS: In total, 183, 66, 11, and 28 patients were classified into DISFORM I, II, III, and IV groups, respectively. In the DISFORM I, II, III, and IV groups, the PP rates were 75.3%, 91.1%, 87.5%, and 50.0%, respectively, and freedom from CD-TLR rates were 86.0%, 91.6%, 88.9%, and 76.7%, respectively, at 12 months. In the DISFORM I-III and IV groups, the PP rates were 79.4% and 50.0%, respectively, and freedom from CD-TLR rates were 87.5% and 76.7%, respectively, at 12 months. Multivariate analysis showed that chronic limb-threatening ischemia, DISFORM IV, and Lutonix™ use were independent predictors of PP loss at 12 months. CONCLUSION: DISFORM IV had a lower PP rate than DISFORM I-III in midterm phase.

LMT AMI Caused by a Valve-Like Ridge in a 9-Year-Old Boy Successfully Treated With PCI.

A 9-year-old boy was suspected of having acute myocardial infarction and emergency coronary angiogram was performed. No signs of flow limitation in either coronary artery was detected. We performed intravascular ultrasonography from the ascending aorta, which showed a ridge on the left main trunk acting like a valve, resulting in significant stenosis. Percutaneous coronary intervention with stent deployment was performed with good result.

Effectiveness and safety of morphine administration for refractory dyspnoea among hospitalised patients with advanced heart failure: the Morphine-HF study.

OBJECTIVES: Morphine is effective in alleviating dyspnoea in patients with cancer. We aimed to investigate the effectiveness and safety of morphine administration for refractory dyspnoea in patients with advanced heart failure (HF). METHODS: We conducted a multicentre, prospective, observational study of hospitalised patients with advanced HF in whom morphine was administered for refractory dyspnoea. Morphine effectiveness was evaluated by dyspnoea intensity changes, assessed regularly by both a quantitative subjective scale (Visual Analogue Scale (VAS; graded from 0 to 100 mm)) and an objective scale (Support Team Assessment Schedule-Japanese (STAS-J; graded from 0 to 4 points)). Safety was assessed by vital sign changes and new-onset severe adverse events, including nausea, vomiting, constipation and delirium based on the Common Terminology Criteria for Adverse Events. RESULTS: From 15 Japanese institutions between September 2020 and August 2022, we included 28 hospitalised patients with advanced HF in whom morphine was administered (mean age: 83.8±8.7 years, male: 15 (54%), New York Heart Association class IV: 26 (93%) and mean left ventricular ejection fraction: 38%±19%). Both VAS and STAS-J significantly improved from baseline to day 1 (VAS: 67±26 to 50±31 mm; p=0.02 and STAS-J: 3.3±0.8 to 2.6±1.1 points; p=0.006, respectively), and thereafter the improvements sustained through to day 7. After morphine administration, vital signs including blood pressure, pulse rate and oxygen saturation did not change, and no new-onset severe adverse events occurred through to day 7. CONCLUSIONS: This study suggested acceptable effectiveness and safety for morphine administration in treating refractory dyspnoea in hospitalised patients with advanced HF.

Association between High Bleeding Risk and 2-Year Mortality in Patients with Chronic Limb-Threatening Ischemia.

AIM: Patients with chronic limb-threatening ischemia (CLTI) have a high bleeding risk (HBR) and mortality rate. The 2-year life expectancy is an important factor in deciding the appropriate treatment strategy. This study aimed to assess the influence of HBR on the prognosis of patients with CLTI. METHODS: A total of 259 patients with CLTI who underwent endovascular therapy (EVT) (mean age, 76.2 years; male, 62.9%) between January 2018 and December 2019 were evaluated. The Academic Research Consortium for HBR (ARC-HBR) criteria were applied to each patient, and the ARC-HBR scores were calculated. The cut-off score for predicting all-cause mortality within two years was derived using a survival classification and regression tree (CART) model. Causes of death and the association between ARC-HBR scores and major bleeding events within two years were also investigated. RESULTS: Based on the CART model, patients were divided into three groups (low HBR score 0-1.0, 48 patients; moderate HBR score 1.5-3.0, 176 patients; and high HBR score ≥ 3.5, 35 patients). During the study period, 82 patients (39.6%) died due to cardiac (n=23) and non-cardiac causes (n=59). All-cause mortality increased significantly with increasing ARC-HBR scores. Cox multivariate analysis revealed a significant association between high ARC-HBR scores and the risk of all-cause mortality within two years. Major bleeding events increased significantly with increasing ARC-HBR scores. CONCLUSIONS: The ARC-HBR score could predict 2-year mortality in patients with CLTI who underwent EVT. Thus, this score can help determine the best revascularization strategy for patients with CLTI.

Predictors of recurrence based on intravascular ultrasound findings after Eluvia placement in symptomatic peripheral arterial disease: A retrospective study.

Background and Aims: Polymer-coated drug-eluting stents (Eluvia) have shown favorable clinical outcomes in real-world registries. There are no reports on recurrent predictors after Eluvia placement based on intravascular ultrasound (IVUS) findings. Methods: We analyzed clinical data from the ASIGARU PAD registry, a retrospective, multicenter, observational study that enrolled patients who underwent endovascular therapy for superficial femoral and proximal popliteal arteries lesions using Eluvia or drug-coated balloon. The primary outcome was the identification of recurrent predictors, including IVUS parameters at 12 months. The rate of target lesion recurrence was also assessed. Results: IVUS images were obtained in 54 of 65 cases. Seven recurrent cases (13.0%) were observed within 12 months. The random survival forest method presented eight predictive variables of recurrence: Clinical Frailty Scale (CFS), distal stent edge area, distal plaque burden, age, sex, distal external elastic membrane (EEM) area, minimum stent area (MSA), and distal lumen area. Furthermore, the partial dependence plot showed that frailty (CFS ≥ 6), smaller distal stent edge area, higher and lower distal plaque burden, older and younger age, female sex, smaller distal EEM area, smaller MSA, and smaller and larger distal lumen area predicted recurrence after Eluvia placement within 12 months. Conclusion: CFS, distal stent edge area, distal plaque burden, age, sex, distal EEM area, MSA, and distal lumen area were significant recurrent predictors after Eluvia placement.

A snare maneuver to reposition self-expandable aortic valve after transcatheter replacement of surgically implanted valve.

In this case, we successfully repositioned the transcatheter heart valve (THV) by pulling it with a snare inserted via the right brachial artery. Attempting to pull the THV via the femoral approach was not successful, due to the vector of the pulling force not being coaxial. Changing the direction of the force by switching to an approach from the right brachial artery successfully prevented perivalvular leakage. While there are previous case reports of repositioning an implanted transcatheter valve in a native valve using a gooseneck snare, to our knowledge, this is the first case of successfully repositioning an implanted transcatheter valve in a valve-in-valve procedure using the precise assessment that can be achieved with intra-procedural transesophageal echocardiography. Learning objective: Perivalvular leakage (PVL) is a major problem after transcatheter aortic valve replacement. In this case, we experienced PVL after implantation of self-expandable transcatheter heart valve (THV) inside the previously inserted Mosaic bioprosthetic valve. Depth of the implanted valve was too low into left ventricle accessed with transesophageal echocardiogram. It is barely known whether THV in surgical implanted aortic valve could be repositioned using snare maneuver, but we successfully pulled the valve via brachial artery and PVL was controlled.

Target Lesion Revascularization After Intravascular Ultrasound-Guided Percutaneous Coronary Intervention.

BACKGROUND: Several stent expansion criteria derived from the intravascular ultrasound (IVUS) evaluation have been proposed to predict future clinical outcomes, but optimal stent expansion criteria as a guide during percutaneous coronary intervention (PCI) are still controversial. There are no studies evaluating the utility of stent expansion criteria along with the clinical and procedural factors in predicting target lesion revascularization (TLR) after contemporary IVUS-guided PCI. METHODS: OPTIVUS-Complex PCI study (Optimal Intravascular Ultrasound Guided Complex Percutaneous Coronary Intervention) multivessel cohort was a prospective multicenter study enrolling 961 patients undergoing multivessel PCI including left anterior descending coronary artery using IVUS with an intention to meet the prespecified criteria for optimal stent expansion. We compared several stent expansion criteria (minimum stent area [MSA], MSA/distal or average reference lumen area, MSA/distal or average reference vessel area, OPTIVUS criteria, IVUS-XPL [Impact of Intravascular Ultrasound Guidance on Outcomes of Xience Prime Stents in Long Lesions] criteria, ULTIMATE [Intravascular Ultrasound Guided Drug Eluting Stents Implantation in "All-Comers" Coronary Lesions] criteria, and modified MUSIC [Multicenter Ultrasound Stenting in Coronaries Study] criteria) as well as clinical, angiographic, and procedural characteristics between lesions with and without TLR. RESULTS: Among 1957 lesions, the cumulative 1-year incidence of lesion-based TLR was 1.6% (30 lesions). Hemodialysis, treatment of proximal left anterior descending coronary artery lesions, calcified lesions, small proximal reference lumen area, and small MSA had univariate associations with TLR, while all of the stent expansion criteria except for MSA were not associated with TLR. The independent risk factors of TLR were calcified lesions (hazard ratio, 2.34 [95% CI, 1.03-5.32]; P=0.04) and small proximal reference lumen area (Tertile 1: hazard ratio, 7.01 [95% CI, 1.45-33.93]; P=0.02; and Tertile 2: hazard ratio, 5.40 [95% CI, 1.17-24.90]; P=0.03). CONCLUSIONS: In contemporary IVUS-guided PCI practice, the 1-year incidence of TLR was very low. MSA, but not other stent expansion criteria, had univariate association with TLR. Independent risk factors of TLR were calcified lesions and small proximal reference lumen area, although the findings should be interpreted with caution due to small number of TLR events, limited lesion complexity, and short duration of follow-up.

Optimal Intravascular Ultrasound-Guided Percutaneous Coronary Intervention in Patients With Multivessel Disease.

Background: Intravascular ultrasound (IVUS) was only rarely used in landmark trials comparing percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) in patients with multivessel disease. Objectives: The authors aimed to evaluate clinical outcomes after optimal IVUS-guided PCI in patients undergoing multivessel PCI. Methods: The OPTIVUS (OPTimal IntraVascular UltraSound)-Complex PCI study multivessel cohort was a prospective multicenter single-arm study enrolling 1,021 patients undergoing multivessel PCI, including left anterior descending coronary artery using IVUS, aiming to meet the prespecified criteria (OPTIVUS criteria: minimum stent area > distal reference lumen area [stent length ≥28mm], and minimum stent area >0.8 × average reference lumen area [stent length <28mm]) for optimal stent expansion. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE) (death/myocardial infarction/stroke/any coronary revascularization). The predefined performance goals were derived from the CREDO-Kyoto (Coronary REvascularization Demonstrating Outcome study in Kyoto) PCI/CABG registry cohort-2 fulfilling the inclusion criteria in this study. Results: In this study, 40.1% of the patients met OPTIVUS criteria in all stented lesions. The cumulative 1-year incidence of the primary endpoint was 10.3% (95% CI: 8.4%-12.2%), which was significantly lower than the predefined PCI performance goal of 27.5% (P < 0.001), and which was numerically lower than the predefined CABG performance goal of 13.8%. The cumulative 1-year incidence of the primary endpoint was not significantly different regardless of meeting or not meeting OPTIVUS criteria. Conclusions: Contemporary PCI practice conducted in the OPTIVUS-Complex PCI study multivessel cohort was associated with a significantly lower MACCE rate than the predefined PCI performance goal, and with a numerically lower MACCE rate than the predefined CABG performance goal at 1 year.

Angiographic evaluation of radial artery injury after transradial approach for percutaneous coronary intervention.

The transradial approach for percutaneous coronary intervention (TRA-PCI) has been increasingly gaining popularity in clinical practice. However, its association with risk for long-term radial artery injury has not been yet thoroughly defined. We retrospectively examined the patients undergoing radial artery angiography (RAG) after TRA-PCI to determine the incidence and risk factors of radial artery injury. The study included 558 patients undergoing follow-up radial artery angiography at 12 month after TRA-PCI. Radial artery injury occurred in 140 patients (25%) with 3 distinct morphological patterns: focal radial artery stenosis (RAS) P.7,7: in 7 patients (1%), diffuse radial artery stenosis (RAS) in 78 patients (14%), and radial artery occlusion (RAO) in 55 patients (10%). Patients with RAS/RAO were more likely to be female, had smaller height and body weight, smaller body mass index and smaller body surface area (BSA) as compared with those without RAS/RAO. Multivariable logistic regression analysis identified BSA (odds ratio, 1.34 per 0.1 m2 increase; 95% confidence interval, 1.07-1.71; p = 0.01) and a history of TRA-PCI (odds ratio, 2.35; 95% confidence interval, 1.16-5.08; p = 0.017) as independent predisposing factors of radial artery injury. In a sub-analysis of 323 patients undergoing both pre-PCI RAG and follow-up RAG, pre-PCI radial diameter as well as BSA and a history of TRA-PCI were independently associated with radial artery injury. Long-term injury after TRA-PCI is considerably common and care should be paid for RAS/RAO, especially for those patients with lower BSA, history of TRA-PCI and small radial artery diameter.

Circulating markers of collagen types I, III, and IV in patients with dilated cardiomyopathy: relationships with myocardial collagen expression.

AIMS: Collagen-derived peptides such as collagen I C-terminal telopeptide (CITP) and procollagen III N-terminal propeptide (PIIINP) have been conventionally used as markers of cardiac fibrosis. Collagen IV 7S domain (P4NP 7S) has been recently reported to be correlated with haemodynamics in patients with acute heart failure. We investigated whether these markers reflect cardiac remodelling and myocardial collagen expression. METHODS AND RESULTS: In 80 patients with dilated cardiomyopathy, relationships of CITP, PIIINP, and P4NP 7S to clinical and echocardiographic variables were analysed. CITP and PIIINP were inversely correlated with estimated glomerular filtration rate (r = -0.41, P < 0.001 and r = -0.32, P = 0.004, respectively); P4NP 7S was positively correlated with B-type natriuretic peptide (r = 0.32, P = 0.003) and γ-glutamyltransferase (r = 0.38, P < 0.001). These correlations were significant even after adjustment by potential confounders, whereas all three collagen markers were not independently correlated with ejection fraction nor with left ventricular (LV) diastolic diameter. In 33 patients undergoing endomyocardial biopsy, myocardial collagen I and III mRNA expressions were correlated with LV end-diastolic volume index (r = 0.42, P = 0.02 and r = 0.54, P = 0.002, respectively), whereas myocardial collagen IV mRNA expression was not correlated with LV end-diastolic volume index nor with ejection fraction. Each collagen-derived peptide was not significantly correlated with the myocardial expression of their corresponding collagen mRNA. CONCLUSIONS: Our study shows that CITP, PIIINP, and P4NP 7S do not reflect myocardial collagen mRNA expression but presumably reflect extra-cardiac organ injury in heart failure.

Liver fibrogenesis marker, 7S domain of collagen type IV in patients with acutely decompensated heart failure: Correlates, prognostic value and time course.

BACKGROUND: Congestion in heart failure (HF) induces multiple organ injury, which may cause remodeling of extracellular matrix. We hypothesized that liver fibrogenesis marker, 7S domain of collagen type IV (P4NP 7S) was correlated with congestion and liver injury in HF. METHODS AND RESULTS: We measured serum P4NP 7S in two cohorts. Cohort 1 included 70 patients undergoing catheterization. P4NP 7S was correlated with pulmonary capillary wedge pressure, right ventricular and atrial pressure (r=0.50, P<0.001, r=0.42, P<0.001, r=0.39, P=0.001, respectively) but not with cardiac index (r=-0.05. P=0.7). Cohort 2 included 145 patients with acute HF, in whom we serially measured P4NP 7S at admission, discharge, early (1-month) and late (6-month) post-discharge period. γ-Glutamyltransferase and B-type natriuretic peptide were independently correlated with P4NP 7S at discharge. The cumulative 1-year incidence of death or HF hospitalization was much higher in the 3rd tertile of P4NP 7S than in the 1st and 2nd tertiles (50%, 25%, and 24%, Log-rank P=0.004). P4NP 7S enhanced risk classification when added to conventional risk factors (net reclassification improvement=0.47, P=0.02). In patients without early readmission, P4NP 7S decreased during hospitalization and remained low for up to 6months, whereas in patients with early readmission, P4NP 7S was persistently elevated during hospitalization, further increased at second admission, and remained high at 6months. CONCLUSION: P4NP 7S was correlated with hemodynamics. The results shed new light on the pathophysiology of HF.