Clinical outcomes of catheter ablation for atrial fibrillation, atrial flutter, and atrial tachycardia in wild-type transthyretin amyloid cardiomyopathy: a proposed treatment strategy for catheter ablation in each arrhythmia.

AIMS: Wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) is often accompanied by atrial fibrillation (AF), atrial flutter (AFL), and atrial tachycardia (AT), which are difficult to control because beta-blockers and antiarrhythmic drugs can worsen heart failure (HF). This study aimed to investigate the outcomes of catheter ablation (CA) for AF/AFL/AT in patients with ATTRwt-CM and propose a treatment strategy for CA. METHODS AND RESULTS: A cohort study was conducted on 233 patients diagnosed with ATTRwt-CM, including 54 who underwent CA for AF/AFL/AT. The background of each arrhythmia and the details of the CA and its outcomes were investigated. The recurrence-free rate of AF/AFL/AT overall in ATTRwt-CM patients with multiple CA was 70.1% at 1-year, 57.6% at 2-year, and 44.0% at 5-year follow-up, but CA significantly reduced all-cause mortality [hazard ratio (HR): 0.342, 95% confidence interval (CI): 0.133-0.876, P = 0.025], cardiovascular mortality (HR: 0.378, 95% CI: 0.146-0.981, P = 0.045), and HF hospitalization (HR: 0.488, 95% CI: 0.269-0.889, P = 0.019) compared with those without CA. There was no recurrence of the cavotricuspid isthmus (CTI)-dependent AFL, non-CTI-dependent simple AFL terminated by one linear ablation, and focal AT originating from the atrioventricular (AV) annulus or crista terminalis eventually. Twelve of 13 patients with paroxysmal AF and 27 of 29 patients with persistent AF did not have recurrence as AF. However, all three patients with non-CTI-dependent complex AFL not terminated by a single linear ablation and 10 of 13 cases with focal AT or multiple focal ATs originating beyond the AV annulus or crista terminalis recurred even after multiple CA. CONCLUSION: The outcomes of CA for ATTRwt-CM were acceptable, except for multiple focal AT and complex AFL. Catheter ablation may be aggressively considered as a treatment strategy with the expectation of improving mortality and hospitalization for HF.

Coronary Stent Evaluation by CTA: Image Quality Comparison Between Super-Resolution Deep Learning Reconstruction and Other Reconstruction Algorithms.

BACKGROUND. A super-resolution deep learning reconstruction (SR-DLR) algorithm may provide better image sharpness than earlier reconstruction algorithms and thereby improve coronary stent assessment on coronary CTA. OBJECTIVE. The purpose of our study was to compare SR-DLR and other reconstruction algorithms in terms of image quality measures related to coronary stent evaluation in patients undergoing coronary CTA. METHODS. This retrospective study included patients with at least one coronary artery stent who underwent coronary CTA between January 2020 and December 2020. Examinations were performed using a 320-row normal-resolution scanner and were reconstructed with hybrid iterative reconstruction (HIR), model-based iterative reconstruction (MBIR), normal-resolution deep learning reconstruction (NR-DLR), and SR-DLR algorithms. Quantitative image quality measures were determined. Two radiologists independently reviewed images to rank the four reconstructions (4-point scale: 1 = worst reconstruction, 4 = best reconstruction) for qualitative measures and to score diagnostic confidence (5-point scale: score ≥ 3 indicating an assessable stent). The assessability rate was calculated for stents with a diameter of 3.0 mm or less. RESULTS. The sample included 24 patients (18 men, six women; mean age, 72.5 ± 9.8 [SD] years), with 51 stents. SR-DLR, in comparison with the other reconstructions, yielded lower stent-related blooming artifacts (median, 40.3 vs 53.4-58.2), stent-induced attenuation increase ratio (0.17 vs 0.27-0.31), and quantitative image noise (18.1 vs 20.9-30.4 HU) and higher in-stent lumen diameter (2.4 vs 1.7-1.9 mm), stent strut sharpness (327 vs 147-210 ΔHU/mm), and CNR (30.0 vs 16.0-25.6) (all p < .001). For both observers, all ranked measures (image sharpness; image noise; noise texture; delineation of stent strut, in-stent lumen, coronary artery wall, and calcified plaque surrounding the stent) and diagnostic confidence showed a higher score for SR-DLR (median, 4.0 for all features) than for the other reconstructions (range, 1.0-3.0) (all p < .001). The assessability rate for stents with a diameter of 3.0 mm or less (n = 37) was higher for SR-DLR (86.5% for observer 1 and 89.2% for observer 2) than for HIR (35.1% and 43.2%), MBIR (59.5% and 62.2%), and NR-DLR (62.2% and 64.9%) (all p < .05). CONCLUSION. SR-DLR yielded improved delineation of the stent strut and in-stent lumen, with better image sharpness and less image noise and blooming artifacts, in comparison with HIR, MBIR, and NR-DLR. CLINICAL IMPACT. SR-DLR may facilitate coronary stent assessment on a 320-row normal-resolution scanner, particularly for small-diameter stents.

Clinical, electrocardiographic, and echocardiographic parameters associated with the development of pacing and implantable cardioverter-defibrillator indication in patients with transthyretin amyloid cardiomyopathy.

AIMS: This study aimed to identify factors for attention leading to future pacing device implantation (PDI) and reveal the necessity of prophylactic PDI or implantable cardioverter-defibrillator (ICD) implantation in transthyretin amyloid cardiomyopathy (ATTR-CM) patients. METHODS AND RESULTS: This retrospective single-center observational study included consecutive 114 wild-type ATTR-CM (ATTRwt-CM) and 50 hereditary ATTR-CM (ATTRv-CM) patients, neither implanted with a pacing device nor fulfilling indications for PDI at diagnosis. As a study outcome, patient backgrounds were compared with and without future PDI, and the incidence of PDI in each conduction disturbance was examined. Furthermore, appropriate ICD therapies were investigated in all 19 patients with ICD implantation. PR-interval ≥220 msec, interventricular septum (IVS) thickness ≥16.9 mm, and bifascicular block were significantly associated with future PDI in ATTRwt-CM patients, and brain natriuretic peptide ≥35.7 pg/mL, IVS thickness ≥11.3 mm, and bifascicular block in ATTRv-CM patients. The incidence of subsequent PDI in patients with bifascicular block at diagnosis was significantly higher than that of normal atrioventricular (AV) conduction in both ATTRwt-CM [hazard ratio (HR): 13.70, P = 0.019] and ATTRv-CM (HR: 12.94, P = 0.002), whereas that of patients with first-degree AV block was neither (ATTRwt-CM: HR: 2.14, P = 0.511, ATTRv-CM: HR: 1.57, P = 0.701). Regarding ICD, only 2 of 16 ATTRwt-CM and 1 of 3 ATTRv-CM patients received appropriate anti-tachycardia pacing or shock therapy, under the number of intervals to detect for ventricular tachycardia of 16-32. CONCLUSIONS: According to our retrospective single-center observational study, prophylactic PDI did not require first-degree AV block in both ATTRwt-CM and ATTRv-CM patients, and prophylactic ICD implantation was also controversial in both ATTR-CM. Larger prospective, multi-center studies are necessary to confirm these results.

Cost-Effectiveness of Vonoprazan Compared With Proton Pump Inhibitors in Patients Taking Low-Dose Aspirin for Secondary Prevention of Cardiovascular Events in Japan.

BACKGROUND: Low-dose aspirin (LDA) is used to prevent recurrent cardiovascular (CV) events, but is associated with upper gastrointestinal (GI) bleeding; concomitant use of a proton pump inhibitor (PPI) reduces this risk. This study aimed to assess the cost-effectiveness of vonoprazan compared with PPIs (lansoprazole and esomeprazole) in patients taking LDA for secondary prevention of CV events.Methods and Results: A Markov simulation model was developed to predict the number of GI bleeding and acute CV events using 3 strategies (vonoprazan+LDA, esomeprazole+LDA, and lansoprazole+LDA), which were translated into quality-adjusted life-years (QALYs) and costs. Transition probabilities and utilities were derived from the results of published literature, and medical costs were based on the Japanese National Health Insurance fee table and claims databases in 2020. Outcomes were projected over 30 years starting at age 65 years and discounted at 2% annually. Expected costs with esomeprazole 20 mg, lansoprazole 15 mg and vonoprazan 10 mg were JPY 1,225,657, JPY 943,930, and JPY 1,059,510, respectively. The QALY gain for vonoprazan vs. esomeprazole was 0.35, thus vonoprazan was dominant against esomeprazole. The QALY gain for vonoprazan vs. lansoprazole was 0.29 and the incremental cost-effectiveness ratio (ICER) was JPY 398,551, thus, vonoprazan was more cost-effective than lansoprazole. CONCLUSIONS: Vonoprazan is dominant or cost-effective compared with esomeprazole and lansoprazole in patients taking LDA for secondary prevention of CV events.

Sex Differences in Long-Term Outcomes in Patients With Chronic Coronary Syndrome After Percutaneous Coronary Intervention　- Insights From a Japanese Real-World Database Using a Storage System.

BACKGROUND: Several studies have reported some sex differences in patients with coronary artery diseases. However, the results regarding long-term outcomes in patients with chronic coronary syndrome (CCS) are inconsistent. Therefore, the present study investigated sex differences in long-term outcomes in patients with CCS after percutaneous coronary intervention (PCI).Methods and Results: This was a retrospective, multicenter cohort study. We enrolled patients with CCS who underwent PCI between April 2013 and March 2019 using the Clinical Deep Data Accumulation System (CLIDAS) database. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, or hospitalization for heart failure. In all, 5,555 patients with CCS after PCI were included in the analysis (4,354 (78.4%) men, 1,201 (21.6%) women). The median follow-up duration was 917 days (interquartile range 312-1,508 days). The incidence of MACE was not significantly different between the 2 groups (hazard ratio [HR] 1.20; 95% confidential interval [CI] 0.97-1.47; log-rank P=0.087). After performing multivariable Cox regression analyses on 4 different models, there were still no differences in the incidence of MACE between women and men. CONCLUSIONS: There were no significant sex differences in MACE in patients with CCS who underwent PCI and underwent multidisciplinary treatments.

Relationship between coronary artery calcium score and bleeding events after percutaneous coronary intervention in chronic coronary syndrome.

The relationship between coronary artery calcium (CAC) and bleeding events after percutaneous coronary intervention (PCI) in patients with chronic coronary syndrome (CCS) is not well established. This study aimed to examine the association between CAC scores and clinical outcomes after PCI in patients with CCS. This retrospective observational study included 295 consecutive patients who underwent multidetector computer tomography and were scheduled for their first elective PCI. Patients were categorized into two groups based on the CAC scores (low: ≤ 400 or high: > 400). The bleeding risk was evaluated using the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria. The primary clinical outcome was a major bleeding event within 1 year after PCI, defined as Bleeding Academic Research Consortium (BARC) 3 or 5. The high CAC score group had a higher proportion of patients meeting the ARC-HBR criteria than the low CAC score group (52.7% vs. 31.3%, p < 0.001). Kaplan-Meier survival analysis showed that the incidence of major bleeding events was higher in the high CAC score group as compared to the low CAC score group (p < 0.001). Furthermore, multivariate Cox regression anal ysis revealed that a high CAC score was an independent determinant of major bleeding events during the first year after PCI. A high CAC score is significantly associated with the incidence of major bleeding events after PCI in CCS patients.

Utility of the Total Thrombus-Formation Analysis System as a Tool for Evaluating Thrombogenicity and Monitoring Antithrombotic Therapy in Pediatric Fontan Patients.

BACKGROUND: There is no consensus regarding thromboprophylaxis after Fontan procedure, and novel tools to assess thrombogenicity are needed to establish optimal thromboprophylaxis. The Total Thrombus-formation Analysis System (T-TAS) was developed for the quantitative analysis of thrombus formation using microchips with thrombogenic surfaces. This prospective study evaluated the utility of T-TAS in the assessment of thrombogenicity in pediatric Fontan patients. METHODS AND RESULTS: The participants included 20 consecutive Fontan patients who underwent cardiac catheterization and 30 healthy controls. Blood samples collected without and with antithrombotic therapy (aspirin or aspirin and warfarin) were used for T-TAS to compute the area under the curve (AUC) in the atheroma (AR10-AUC30) and platelet (PL18-AUC10) chips. A higher AUC indicates higher thrombogenicity. T-TAS values showed that patients in the Fontan group without antithrombotic therapy had lower thrombogenicity than those in the control group [PL18-AUC10, median (interquartile range) 356 (313-394) vs. 408 (392-424); AR10-AUC30, median (interquartile range) 1270 (1178-1351) vs. 1382 (1338-1421)]. Aspirin and warfarin therapies significantly decreased PL18-AUC10 and AR10-AUC30, respectively, compared with those of patients without antithrombotic therapy (P < 0.001 for each comparison). Subgroup analysis divided by low (< 9 mmHg) or high (≥ 9 mmHg) central venous pressure (CVP) showed that CVP affects the reduction in AR10-AUC30 with antithrombotic therapy. CONCLUSIONS: T-TAS may be a useful tool for monitoring thrombogenicity and antithrombotic therapy in Fontan patients.

ß-Blockers are associated with increased B-type natriuretic peptide levels differently in men and women in heart failure with preserved ejection fraction.

ß-Blocker (BB) use is a mainstay for the treatment of heart failure (HF) with reduced ejection fraction (HFrEF), whereas its efficacy for heart failure with preserved ejection fraction (HFpEF) remains controversial. Women outnumber men in HFpEF, whereas men outnumber women in HFrEF. Plasma B-type natriuretic peptide (BNP) is established as a biomarker for HF. We examined whether BB use is associated with plasma BNP levels differently in men and women with HFpEF. The study subjects comprised 721 patients with HFpEF [left ventricular ejection fraction (LVEF) ≥ 50%] (184 men, mean age 78.2 ± 9.2 yr and 537 women, mean age 83.1 ± 8.8 yr), 179 on BB (66 men and 113 women) and 542 no BB (118 men and 424 women), 583 in sinus rhythm (SR) and 138 in atrial fibrillation (AF). A multivariable logistic regression test was used. Plasma BNP levels were higher (P = 0.0005), systolic blood pressure and LVEF lower (P = 0.0003, and P = 0.0059, respectively) on BBs than on no BBs in women, whereas in men, plasma BNP levels, systolic blood pressure, and LVEF were not altered significantly (P = 0.0849, P = 0.9129, and P = 0.4718, respectively) on BBs compared with no BBs in patients with SR. Multivariable logistic regression analysis revealed that BB use and women were a positive and a negative predictor for high BNP levels (P = 0.003 and P = 0.032, respectively) in SR but not in AF. BB use was associated with high-plasma BNP levels and lower LVEF in women but not in men with HFpEF and SR, suggesting that the pathogenesis and treatment of HFpEF may differ in men and women in SR.NEW & NOTEWORTHY Pathogenesis and treatment for heart failure with preserved ejection fraction (HFpEF) may differ in men and women in sinus rhythm (SR).

Increased thrombogenicity is associated with revascularization outcomes in patients with chronic limb-threatening ischemia.

OBJECTIVES: Clinically driven target lesion revascularization (CD-TLR) frequently occurs after endovascular therapy (EVT) in patients with chronic limb-threatening ischemia (CLTI). The total thrombus-formation analysis system (T-TAS) can quantitatively evaluate thrombogenicity. Therefore, we aimed to elucidate the association of the T-TAS parameters with CD-TLR. METHODS: We analyzed 34 patients with CLTI and 62 patients without CLTI who had undergone EVT. Blood samples collected on the day of EVT were used in the T-TAS to compute the thrombus formation area under the curve for the first 10 minutes for the platelet chip tested at a flow rate of 24 µL/min (PL24-AUC10) and area under the curve for the first 30 minutes for the atheroma chip tested at a flow rate of 10 µL/min (AR10-AUC30). After EVT, clinical follow-up was performed, and the presence of CD-TLR was assessed. RESULTS: During the follow-up period (median, 574 days), 10 patients (29%) in the CLTI group and 11 (18%) in the non-CLTI group had required CD-TLR. In the CLTI group, the patients with CD-TLR had had a higher AR10-AUC30 vs those without (median, 1694 [interquartile range, 1657-1799] vs median, 1561 [interquartile range, 1412-1697]; P = .01). In contrast, the PL24-AUC10 showed no significant differences when stratified by CD-TLR in either group. For the CLTI patients, multivariable Cox regression analysis using propensity score matching revealed that the AR10-AUC30 was an independent predictor of CD-TLR even after adjusting for baseline demographics, lesion characteristics, and anticoagulant use (hazard ratio, 2.04; 95% confidence interval, 1.18-3.88; P = .01; per 100-unit increase). In contrast, for those without CLTI, neither the AR10-AUC30 nor the PL24-AUC10 was significantly associated with CD-TLR. Receiver operating characteristics curve analysis identified an AR10-AUC30 level of 1646 as an optimal cutoff value to predict for CD-TLR (AUC, 0.85; sensitivity, 0.93; specificity, 0.56). CONCLUSIONS: For patients with CLTI, but not for those without CLTI, the AR10-AUC30 showed potential to predict for CD-TLR. This finding suggests that hypercoagulability might play a predominant role in the progression of CLTI and that anticoagulant therapy might be useful in preventing revascularization.

Clinical Characteristics and Outcomes of Patients Presenting With Acute Myocardial Infarction Without Cardiogenic Shock.

BACKGROUND: Most patients with acute myocardial infarction (AMI) present in the emergency department in a hemodynamically stable condition (i.e., non-cardiogenic shock) (AMI-NCS). However, few studies specifically focused on the clinical characteristics and outcomes of AMI-NCS patients. Temporal trends in clinical characteristics, in-hospital occurrence of in-hospital adverse outcomes, and the effect of primary percutaneous coronary intervention (PPCI) were examined.Methods and Results: Between April 2012 and March 2018, 176,275 AMI-NCS patients (67.7% of the total AMI population; 25.4% female; mean age 68.6±13.1 years) were identified in a nationwide Japanese administrative database. During the 6-year study period, AMI-NCS patients have been getting older and had an increasing burden of comorbidities. The rates of 30-day all-cause mortality and in-hospital complications were 2.6% and 30.5%, respectively. Thirty-day all-cause mortality did not change significantly over time, whereas in-hospital complications, especially major non-cardiac events, increased progressively. On multivariable analyses, higher age, higher Killip class, atrial fibrillation, chronic renal failure, and malignancy were independently associated with both increased 30-day mortality and in-hospital complications. PPCI was independently associated with lower mortality and in-hospital complications. CONCLUSIONS: The clinical background of AMI-NCS patients has been becoming more complex with increasing age and the burden of comorbidities, with increased in-hospital complications. More active and appropriate application of PPCI may further decrease adverse events and improve survival of AMI-NCS patients.

Malnutrition-associated high bleeding risk with low thrombogenicity in patients undergoing percutaneous coronary intervention.

BACKGROUND AND AIMS: Although antithrombotic treatments are established for coronary artery disease (CAD), they increase the bleeding risk, especially in malnourished patients. The total thrombus-formation analysis system (T-TAS) is useful for the assessment of thrombogenicity in CAD patients. Here, we examined the relationships among malnutrition, thrombogenicity and 1-year bleeding events in patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: This was a retrospective analysis of 300 consecutive CAD patients undergoing PCI. Blood samples obtained on the day of PCI were used in the T-TAS to compute the thrombus formation area under the curve. We assigned patients to two groups based on the geriatric nutritional risk index (GNRI): 102 patients to the lower GNRI group (≤98), 198 patients to the higher GNRI group (98<). The primary endpoint was the incidence of 1-year bleeding events defined by Bleeding Academic Research Consortium criteria types 2, 3, or 5. The T-TAS levels were lower in the lower GNRI group than in the higher GNRI group. Kaplan-Meier analysis showed worse 1-year bleeding event-free survival in the lower GNRI group compared with the higher GNRI group. The combined model of the GNRI and the Academic Research Consortium for High Bleeding Risk (ARC-HBR) had good calibration and discrimination for bleeding risk prediction. In addition, having a lower GNRI and ARC-HBR positivity was associated with 1-year bleeding events. CONCLUSION: A lower GNRI could reflect low thrombogenicity evaluated by the T-TAS and determine bleeding risk in combination with ARC-HBR positivity.

Impact of cerebrovascular comorbidity on prognosis in Japanese patients undergoing PCI: 1-year data from Japanese multicenter registry (KICS).

Cardiovascular and cerebrovascular diseases are considered the principal cause of morbidity and mortality worldwide; the effect of stroke-induced cardiac manifestations is well recognized; however, not enough clinical data have been found about the impact of stroke with underlying cardiac disease. This study's objective is to assess the impact of stroke on the prognosis of patients with underlying IHD, who underwent PCI treatment. This was a multicenter, 1-year observational study in patients undergoing PCI in one of the 17 participating centers across Japan. 18,495 patients were registered on the PCI list; 2481 patients had a prior stroke experience, whereas 15,979 were stroke-free. Our study revealed that stroke patients were significantly older (mean age 73.5 ± 9.6, 69.7(± 11.5), respectively), and suffered from more comorbidities (diabetes, hypertension, and chronic kidney disease, p < 0.0001). During the 1-year period, subjects with stroke showed higher incidence of clinical events compared to those without stroke; to illustrate, all-cause death accounted for 6.2% in patients with stroke, in contrast to only 2.8% in stroke-free patients (p < 0.0001), cardiac death amounted for 2.2 and 1.2%, respectively (p < 0.0001), recurrent stroke for 3.1% and 1.2% (p < 0.0001), non-cardiac death for 3.6 and 1.54% (p < 0.0001), and finally, hemorrhagic complications with 2.6 and 1.3% (p < 0.0001). Kaplan-Meier analysis revealed that stroke patients had a higher probability of all-cause mortality, cardiac death, and recurrent stroke (log-rank p < 0.0001). Cox hazard analysis also showed that the presence of stroke is a significant indicator in determining the outcome of cardiac death (HR = 1.457, 95% CI 1.036-2.051, p = 0.031); hence, proving it to be a crucial predictor on cardiac prognosis. History of prior stroke was common in PCI patients, and independently associated with a higher rate of subsequent cardiovascular and cerebrovascular events recurrence. Thus, highlighting an urgent need for comprehensive prevention of cardiac and cerebrovascular diseases.

Incidence Rate of Acute Coronary Syndrome Including Acute Myocardial Infarction, Unstable Angina, and Sudden Cardiac Death in Nobeoka City for the Super-Aged Society of Japan.

BACKGROUND: This study aimed to calculate incidence rates (IR) of acute coronary syndrome (ACS) including acute myocardial infarction (AMI), unstable angina (UAP), and sudden cardiac death (SCD) in Nobeoka city, Japan.Methods and Results:This was an observational study based on a city-wide comprehensive registration between 2015 and 2017 in Nobeoka city, Japan, using 2 databases: all patients with cardiogenic out-of-hospital cardiac arrest in Nobeoka city and hospitalized ACS patients from Miyazaki Prefectural Nobeoka Hospital in which all ACS patients in Nobeoka city were hospitalized except for possible rare cases of patients highly unlikely to be hospitalized elsewhere. The IRs of ACS based on the population size of Nobeoka city (125,000 persons), and their age-adjusted IRs by using the direct method and the 2015 model population of Japan were calculated. There were 260 eligible patients hospitalized with first-onset ACS (age [SD]=71.1 [12.4], 34.2% women) and 107 eligible SCD patients. Crude IRs of hospitalized ACS and SCD patients, and hospitalized AMI and SCD patients, respectively, were 130.2 (183.3 for men, 85.6 for women) and 107.5 (148.4 for men, 73.2 for women) per 100,000. Crude IRs of hospitalized ACS, AMI, and UAP patients, respectively, were 92.3 (132.8 for men, 58.1 for women), 69.6 (97.9 for men, 45.7 for women), and 22.7 (35.0 for men, 12.4 for women) per 100,000. CONCLUSIONS: The calculated IRs can be useful in building a health strategy for treating ACS.

Risk Prediction Score for Cancer Development in Patients With Acute Coronary Syndrome.

BACKGROUND: Cancer is a known prognostic factor in patients with acute coronary syndrome (ACS), but few risk assessments of cancer development after ACS have been established.Methods and Results:Of the 573 consecutive ACS admissions between January 2015 and March 2018 in Nobeoka City, Japan, 552 were analyzed. Prevalent cancer was defined as a treatment history of cancer, and incident cancer as post-discharge cancer incidence. The primary endpoint was post-discharge cancer incidence, and the secondary endpoint was all-cause death during follow-up. All-cause death occurred in 9 (23.1%) patients with prevalent cancer, and in 17 (3.5%) without cancer. In the multivariable analysis, prevalent cancer was associated with all-cause death. To develop the prediction model for cancer incidence, 21 patients with incident cancer and 492 without cancer were analyzed. We compared the performance of D-dimer with that of the prediction model, which added age (≥65 years), smoking history, and high red blood cell distribution width to albumin ratio (RAR) to D-dimer. The areas under the receiver-operating characteristics curves of D-dimer and the prediction model were 0.619 (95% confidence interval: 0.512-0.725) and 0.774 (0.676-0.873), respectively. Decision curve analysis showed superior net benefits of the prediction model. CONCLUSIONS: By adding elderly, smoking, and high RAR to D-dimer to the prediction model it became clinically useful for predicting cancer incidence after ACS.

Impact of combined baseline and postprocedural troponin values on clinical outcome following the MitraClip procedure.

OBJECTIVES: The purpose of this study was to investigate the impact of periprocedural troponin levels on clinical outcome following the MitraClip procedure. BACKGROUND: Cardiac troponin is known to be a predictive biomarker for various clinical outcomes; however, data about its predictive value in patients undergoing transcatheter mitral valve repair are limited. METHODS: Consecutive patients undergoing the MitraClip procedure were enrolled. Serum cardiac troponin I concentrations were measured before and after the procedure, and the maximal value recorded within 72 hr after the procedure was used for the postprocedural values. The clinical outcome was all-cause mortality within a 1-year follow-up. RESULTS: Out of 354 patients, 29 patients (8.2%) were deceased within 1 year. Patients who died had significantly higher baseline (0.05 [0.01-0.08] vs. 0.01 [0.01-0.03] ng/ml; p < .001) and postprocedural troponin I values (0.51 [0.30-1.42] vs. 0.20 [0.33-0.55] ng/ml; p = .005). A Kaplan-Meier analysis showed that patients with higher baseline troponin I values had a significantly worse prognosis than those with lower values (log-rank p < .001), and similarly, 1-year mortality was significantly higher in patients with higher postprocedural troponin I than those with lower levels (log-rank p = .021). Moreover, the highest mortality rate was observed in patients with both elevated baseline and postprocedural troponin I values (log-rank p = .001), which was found to be an independent predictor of mortality by multivariable analyses. CONCLUSIONS: The present study suggests that combined baseline and postprocedural troponin measurements are useful for risk stratification of 1-year mortality following the MitraClip procedure.

Optical Coherence Tomography-Guided Percutaneous Coronary Intervention With Low-Molecular-Weight Dextran　- Effect on Renal Function.

BACKGROUND: The excessive volume of contrast needed is a significant limitation of optical coherence tomography (OCT)-guided percutaneous coronary intervention (PCI). Low-molecular-weight dextran (LMWD) has been used for OCT image acquisition instead of contrast media. This study compared the effects of OCT-guided PCI using LMWD on renal function and clinical outcomes to those of intravascular ultrasound (IVUS)-guided PCI.Methods and Results:In all, 1,183 consecutive patients who underwent intracoronary imaging-guided PCI were enrolled in this single-center, retrospective, observational study. After propensity score matching, 133 pairs of patients were assigned to undergo either OCT-guided PCI using LMWD or IVUS-guided PCI. There was no significant change from baseline in the primary endpoint, serum creatinine concentrations, after the procedure in either group. There were no significant differences between the OCT and IVUS groups in the volume of contrast medium, the incidence of contrast-induced nephropathy (1.5% vs. 2.3%; P=0.65), and major adverse cardiovascular events (MACE) at 30 days (2.3% vs. 6.0%; P=0.12) and 12 months (2.3% vs. 3.0%; P=0.70) after the procedure. Kaplan-Meier analysis at the 12-month follow-up revealed no significant difference in the incidence of MACE between the 2 groups (P=0.75). CONCLUSIONS: OCT-guided PCI using LMWD did not negatively affect renal function and achieved similar short- and long-term clinical outcomes to IVUS-guided PCI.

Short-term exposure to desert dust and the risk of acute myocardial infarction in Japan: a time-stratified case-crossover study.

Particulate matter from natural sources such as desert dust causes harmful effects for health. Asian dust (AD) increases the risk of acute myocardial infarction (AMI). However, little is known about the risk of myocardial infarction with nonobstructive coronary arteries (MINOCA), compared to myocardial infarction with coronary artery disease (MI-CAD). Using a time-stratified case-crossover design and conditional logistic regression models, the association between short-term exposure to AD whereby decreased visibility (< 10 km) observed at each monitoring station nearest to the hospitals was used for exposure measurements and admission for AMI in the spring was investigated using a nationwide administrative database between April 2012 and March 2016. According to presence of revascularization and coronary atherosclerosis, AMI patients (n = 30,435) were divided into 2 subtypes: MI-CAD (n = 27,202) or MINOCA (n = 3233). The single lag day-2 was used in AD exposure based on the lag effect analysis. The average level of meteorological variables and co-pollutants on the 3 days prior to the case/control days were used as covariates. The occurrence of AD events 2 days before the admission was associated with admission for MINOCA after adjustment for meteorological variables [odds ratio 1.65; 95% confidence interval (CI) 1.18-2.29], while the association was not observed in MI-CAD. The absolute risk difference of MINOCA admission was 1.79 (95% CI 1.21-2.38) per 100,000 person-year. These associations between AD exposure and the admission for MINOCA remained unchanged in two-pollutant models. This study provides evidence that short-term exposure to AD is associated with a higher risk of MINOCA, but not MI-CAD.

Tailored Adjunctive Cilostazol Therapy Based on CYP2C19 Genotyping in Patients With Acute Myocardial Infarction　- The CALDERA-GENE Study.

BACKGROUND: Patients with reduced-function CYP2C19 genotypes on dual antiplatelet therapy (DAPT) with aspirin and clopidogrel show higher clinical risk for acute myocardial infarction (AMI). We investigated the effect of CYP2C19 genotype-tailored adjunctive cilostazol therapy on treatment of AMI.Methods and Results:The study group of 138 patients with suspected AMI were screened for CYP2C19 genotype immediately after percutaneous coronary intervention (PCI) using a SPARTAN RX point-of-care device. Carriers of the CYP2C19 reduced-function allele were randomized into DAPT (Carrier/DAPT) and DAPT plus 14-day cilostazol (Carrier/DAPT+Cilostazol) groups, while noncarriers were treated with DAPT (Noncarrier/DAPT). After exclusion of 10 patients, the remaining 128 patients were analyzed for P2Y12 reaction unit (PRU) using VerifyNow®P2Y12 system, and levels of biomarkers immediately after, and 1, 14, and 28 days after PCI. DAPT+Cilostazol reduced PRU levels in carriers (n=46) to those found in the Noncarrier/DAPT group (n=40), and significantly lower than those of the Carrier/DAPT group (n=42) at 14 days post-PCI. Discontinuation of cilostazol for 14 days was associated with a significant rise in PRU levels to those of the Carrier/DAPT group at 28 days post-PCI. Plasma B-type natriuretic peptide levels at 14 days post-PCI were lower in Carrier/DAPT+Cilostazol than in the other 2 groups, and the levels increased to those of the other groups at 28 days post-PCI after withdrawal of cilostazol. CONCLUSIONS: Adjunctive cilostazol therapy tailored to CYP2C19 genotype seemed useful in AMI patients with the CYP2C19 reduced-function allele.

Akt1-Mediated Muscle Growth Promotes Blood Flow Recovery After Hindlimb Ischemia by Enhancing Heme Oxygenase-1 in Neighboring Cells.

BACKGROUND: Resistance exercise has beneficial effects for patients with peripheral arterial diseases. The hypothesis that muscle growth promotes angiogenesis by interacting with neighboring cells in ischemic lesions was assessed. Methods and Results: Skeletal muscle-specific inducible Akt1 transgenic (Akt1-TG) mice that induce growth of functional skeletal muscles as a model of resistance training were used. Proteomics analysis identified significant upregulation of heme oxigenase-1 (HO-1) in muscle tissue in Akt1-TG mice compared with control mice. Blood flow recovery after hindlimb ischemia was significantly increased in Akt1-TG mice compared with control mice. Enhanced blood flow and capillary density in Akt1-TG mice were completely abolished by the HO-1 inhibitor, Tin-mesoporphyrin. Immunohistochemistry showed that HO-1 expression was not increased in muscle cells, but it was increased in macrophages and endothelial cells. Consistent with these findings, blood flow recovery after hindlimb ischemia was similar between control mice and skeletal muscle-specific HO-1-knockout mice. Adenoviral-mediated overexpression of Akt1 did not increase HO-1 protein expression in C2C12 myotubes; however, the conditioned medium from Akt1-overexpressing C2C12 myotubes increased HO-1 expression in endothelial cells. Cytokine array demonstrated that a panel of cytokine secretion was upregulated in Akt1-overexpressing C2C12 cells, suggesting paracrine interaction between muscle cells and endothelial cells and macrophages. CONCLUSIONS: Akt1-mediated muscle growth improves blood flow recovery after hindlimb ischemia by enhancing HO-1 expression in neighboring cells.