Impact of Sex Differences on Clinical Outcomes in Patients Following Primary Revascularization for Acute Myocardial Infarction　- Insights From the Japanese Nationwide Registry.

BACKGROUND: Women with acute myocardial infarction (AMI) often present a worse risk profile and experience a higher rate of in-hospital mortality than men. However, sex differences in post-discharge prognoses remain inadequately investigated. We examined the impact of sex on 1-year post-discharge outcomes in patients with AMI undergoing percutaneous coronary intervention.Methods and Results: We extracted patient-level data for the period January 2017-December 2018 from the J-PCI OUTCOME Registry, endorsed by the Japanese Association of Cardiovascular Intervention and Therapeutics. One-year all-cause and cardiovascular mortality and major adverse cardiovascular events were compared between men and women. In all, 29,856 AMI patients were studied, with 6,996 (23.4%) being women. Women were significantly older and had a higher prevalence of comorbidities than men. Crude all-cause mortality was significantly higher among women than men (7.5% vs. 5.4% [P<0.001] for ST-elevation myocardial infarction [STEMI]; 7.0% vs. 5.2% [P=0.006] for non-STEMI). These sex-related differences in post-discharge outcomes were attenuated after stratification by age. Multivariate analysis demonstrated an increase in all-cause mortality in both sexes with increasing age and advanced-stage chronic kidney disease (CKD). CONCLUSIONS: Within this nationwide cohort, women had worse clinical outcomes following AMI than men. However, these sex-related differences in outcomes diminished after adjusting for age. In addition, CKD was significantly associated with all-cause mortality in both sexes.

Impact of coronary plaque characteristics on periprocedural myocardial injury in elective percutaneous coronary intervention.

OBJECTIVES: To investigate the relationship between periprocedural myocardial injury (PMI) and plaque characteristics detected by multidetector computed tomography (MDCT) and cardiac magnetic resonance imaging (CMR). MATERIALS AND METHODS: This observational retrospective study, between July 2012 and October 2019, included chronic coronary syndrome patients undergoing elective percutaneous coronary intervention (PCI) after MDCT and CMR. High-intensity plaque (HIP) on non-contrast T1-weighted imaging was defined as a coronary plaque-to-myocardium signal intensity ratio of ≥ 1.4. High-risk plaque (HRP) in MDCT displayed ≥ 2 features: positive remodeling, low-attenuation plaque, spotty calcification, and napkin-ring sign. PMI was defined as an increase in cardiac troponin T levels > 5 times the upper normal limit at 24 h after PCI. RESULTS: Ninety-five target lesions in 76 patients (mean age ± standard deviation, 67 years ± 9; 62 males [82%]) were included. Twenty-one patients (24 lesions) were assigned to the PMI group, while 55 patients (71 lesions) to the non-PMI group. Presence of HRP characteristics on MDCT and HIP on CMR was significantly higher in the PMI group. Multivariate logistic regression analysis showed that HRP in MDCT and HIP in CMR were significant independent predictors of PMI. Target lesions with HRP on MDCT and HIP on CMR were significantly more likely to develop PMI. In 141 plaques with ≥ 50% stenosis (76 patients), patients with PMI had significantly more frequent HRP in MDCT and HIP in CMR in target and non-target lesions. CONCLUSIONS: MDCT and CMR can play an important role in the detection of high-risk lesions for PMI following elective PCI. KEY POINTS: • Multivariate logistic regression analysis showed that high-risk plaque on MDCT and high-intensity plaque on MRI were significant independent predictors of periprocedural myocardial injury (PMI). • Target lesions with high-risk plaque on MDCT and high-intensity plaque on CMR were significantly more likely to develop PMI. • In 141 plaques with ≥ 50% stenosis, patients with PMI were significantly more likely to have high-risk plaques on MDCT and high-intensity plaque on CMR in target and non-target lesions.

Additional Effect of Coronary High-Intensity Plaque on T1-Weighted Magnetic Resonance Imaging With Circulating Malondialdehyde-Modified Low-Density Lipoprotein on Cardiac Events.

BACKGROUND: Although elevated levels of oxidized low-density lipoprotein (LDL) could play a critical role in vulnerable plaque, there are no studies that have compared coronary high-intensity plaque (HIP) and circulating malondialdehyde-modified (MDA)-LDL levels for the prediction of cardiac events.Methods and Results:A total of 139 patients with coronary artery stenosis (>70%) were examined with non-contrast T1-weighted magnetic resonance imaging (MRI) (HIP: n=64, non-HIP: n=75). Scheduled percutaneous coronary intervention (PCI) for culprit lesions was performed within 48 h after MRI. HIP was defined as a signal intensity of coronary plaque to cardiac muscle ratio (PMR) ≥1.4. We evaluated the subsequent major adverse cardiac events (MACE) during the follow-up period (5.6±1.3 years). MDA-LDL levels were independently associated with the presence of HIP (P<0.0001). The incidence of MACE was 15%, and it was significantly higher in patients with HIP (27%) than in those without HIP (5%; P=0.011). Cox proportional hazard analysis showed MDA-LDL levels (P=0.007) and PMR (P=0.016) were significantly associated with MACE. For MACE prediction, C-statistic values for MDA-LDL, PMR, and PMR+MDA-LDL were 0.724, 0.791, and 0.800, respectively. Compared with MDA-LDL alone, the addition of PMR to MDA-LDL increased net reclassification improvement by 0.78 (P=0.012). CONCLUSIONS: MDA-LDL levels might be associated with the presence of HIP in patients with coronary artery disease. Furthermore, adding PMR to MDA-LDL levels markedly improved prediction of subsequent MACE after PCI.

In Vivo Evaluation of Tissue Protrusion by Using Optical Coherence Tomography and Coronary Angioscopy Immediately After Stent Implantation.

BACKGROUND: The relationship between the characteristics of tissue protrusion detected by using optical coherence tomography (OCT) and the findings of coronary angioscopy (CAS) immediately after stent implantation were evaluated.Methods and Results:A total of 186 patients (192 stents) underwent OCT before and after stenting and were observed by using CAS immediately after stenting and at the chronic phase. Patients were assigned to irregular protrusion, smooth protrusion, and disrupted fibrous tissue protrusion groups according to OCT findings. Serum high-sensitivity C-reactive protein (hs-CRP) levels were measured before and after stent implantation. The grade of yellow color (YC) and neointimal coverage (NC), and incidence of thrombus in the stented segment were evaluated by using CAS. After stent implantation, maximum YC grade (smooth, 0.64±0.80; disrupted fibrous tissue, 0.50±0.77; irregular, 1.50±1.09; P<0.0001), a prevalence of Max-YC grade of 2 or 3 (smooth, 17%; disrupted fibrous tissue, 17%; irregular, 50%; P<0.0001) and thrombus (smooth, 15%; disrupted fibrous tissue, 10%; irregular, 69%; P=0.0005), and elevated hs-CRP levels (smooth, 0.22±0.89; disrupted fibrous tissue, -0.05±0.29; irregular, 0.75±1.41; P=0.023) were significantly higher in irregular protrusion than in the other 2 groups. In the chronic phase, maximum- and minimum-NC grade and heterogeneity index, and thrombus did not differ significantly among the 3 groups. CONCLUSIONS: Irregular protrusion was associated with atherosclerotic yellow plaque, incidence of thrombus, and vascular inflammation. The angioscopic findings in the chronic phase may endorse the clinical efficacy of second- and third-drug eluting stents, regardless of the tissue protrusion type.

Impact of coronary artery disease and revascularization on recurrence of atrial fibrillation after catheter ablation: Importance of ischemia in managing atrial fibrillation.

INTRODUCTION: There are few studies analyzing the association between the presence of coronary artery disease (CAD) and recurrence of atrial fibrillation (AF). This study evaluated the clinical impact of concomitant CAD and coronary revascularization on the recurrence of AF after catheter ablation. METHODS AND RESULTS: From April 2008 to December 2015, 700 consecutive patients were treated with pulmonary vein isolation for AF as the initial procedure. Of those, 681 patients who simultaneously underwent coronary angiography were investigated. Patients with at least one coronary stenosis (≥70%) were classified as having obstructive CAD. Of 681 patients, 90 patients had CAD and 42 patients underwent percutaneous coronary intervention (PCI) for lesions with perfusion abnormalities on single-photon emission tomography. The recurrence of AF was significantly more frequent in patients with CAD (56%) than in those without CAD (39%) (P = .0011). On multivariable analysis, the predictors of AF recurrence were persistent or long-standing persistent AF [hazard ratio (HR): 1.36; 95% confidence interval (CI): 1.04-1.77; P = .023], left atrial diameter (HR: 1.04; 95% CI: 1.02-1.06; P < .0001), and concomitant CAD (HR: 1.45; 95% CI: 1.05-1.97; P = .024). The recurrence of AF in patients with PCI (38%) was significantly lower than in those without PCI (72%) (P = .0006), and E/E' significantly improved in patients with PCI (71%) than in those without PCI (42%; P = .001). Performing PCI for concomitant CAD significantly reduced AF recurrence (HR: 0.39; 95% CI: 0.20-0.72; P = .002). CONCLUSION: Patients with CAD had a significantly higher rate of AF recurrence than those without CAD. Coronary revascularization may reduce the recurrence of AF with improvement of left ventricular diastolic function.

Structural relation between the superior vena cava and pulmonary veins in patients with atrial fibrillation.

The superior vena cava (SVC) is a main source of non-pulmonary vein (PV) ectopies that initiate atrial fibrillation (AF). Although the critical role of structural remodeling of the left atrium (LA) in the occurrence of AF was extensively investigated by atrial voltage mapping, that of PVs and the SVC has been less explored. Study subjects comprised 47 patients undergoing catheter ablation of lone AF. During sinus rhythm, PV, SVC, and atrial voltage maps were acquired, and sleeve length of each PV and SVC was determined by an electroanatomical mapping system. The sleeves of the superior PVs were significantly longer than those of the inferior PVs (left superior PV (LSPV): 21 ± 5, left inferior PV: 14 ± 4, right superior PV (RSPV): 19 ± 5, right inferior PV: 15 ± 5, and SVC: 23 ± 10 mm, p < 0.0001). The LSPV sleeve was longer in men than in women (22 ± 6 vs. 19 ± 4 mm, p < 0.05). The sleeve length in the LSPV correlated positively with the body surface area (BSA) (p = 0.003, R = 0.42). Of note, there was a significant correlation in sleeve length between the RSPV and SVC (p < 0.0001, R = 0.64). In conclusion, not right- but left-sided PV sleeves were associated with the BSA of the patients, whereas a structural relation between the right-sided PVs and the SVC was implied based on sleeve mapping. This novel finding may provide mechanistic implications for the development of AF in future studies.

Value of 3-Dimensional Speckle Tracking Echocardiography in the Prediction of Microvascular Obstruction and Left Ventricular Remodeling in Patients With ST-Elevation Myocardial Infarction.

BACKGROUND: In patients with myocardial infarction (MI), microvascular obstruction (MVO) determined by cardiac magnetic resonance imaging (CMR) is associated with left ventricular (LV) remodeling and worse prognosis.Methods and Results:In 71 patients with ST-segment elevation MI (STEMI) treated by primary percutaneous coronary intervention (PCI), speckle tracking echocardiography (STE) and CMR were performed early after PCI. All patients underwent CMR at 6 months after hospital discharge to assess the occurrence of LV remodeling. The values of 3-dimensional (3D)-circumferential strain (CS), area change ratio (ACR), and 2-dimensional (2D)-CS were significantly different for the transmural extent of infarct, whereas the values of 3D- and 2D- longitudinal strain (LS) were not significantly different. In transmural infarct segments, the values of 3D-CS and ACR were significantly lower in segments with MVO than in those without MVO. At 6-month follow-up, LV remodeling was observed in 22 patients. In multivariable logistic regression models, global 3D-CS and ACR were significant determinants of LV remodeling rather than the number of MVO segments. CONCLUSIONS: Regional 3D-CS and ACR reflected the transmural extent of infarct and were significantly associated with the presence of MVO. In addition, global 3D-CS and ACR were preferable to the extent of MVO in the prediction of LV remodeling.

Enhancement patterns detected by multidetector computed tomography are associated with microvascular obstruction and left ventricular remodelling in patients with acute myocardial infarction.

AIMS: This study evaluated the clinical value of myocardial contrast-delayed enhancement (DE) with multidetector computed tomography (MDCT) for detecting microvascular obstruction (MVO) and left ventricular (LV) remodelling revealed by DE magnetic resonance imaging after acute myocardial infarction (AMI). METHODS AND RESULTS: In 92 patients with first AMI, MDCT without iodine reinjection was performed immediately following successful percutaneous coronary intervention (PCI). Delayed-enhancement magnetic resonance imaging performed in the acute and chronic phases was used to detect MVO and LV remodelling (any increase in LV end-systolic volume at 6 months after infarction compared with baseline). Patients were divided into two groups according to the presence (n = 33) or absence (n = 59) of heterogeneous enhancement (HE). Heterogeneous enhancement was defined as concomitant presence of hyper- and hypoenhancement within the infarcted myocardium on MDCT. Microvascular obstruction and LV remodelling were detected in 49 (53%) and 29 (32%) patients, respectively. In a multivariable analysis, HE and a relative CT density >2.20 were significant independent predictors for MVO [odds ratio (OR) 13.5; 95% confidence interval (CI), 2.15-84.9; P = 0.005 and OR 12.0; 95% CI, 2.94-49.2; P < 0.001, respectively). The presence of HE and relative CT density >2.20 showed a high positive predictive value of 93%, and the absence of these two findings yielded a high negative predictive value of 90% for the predictive value of MVO. Heterogeneous enhancement was significantly associated with LV remodelling (OR 6.75; 95% CI, 1.56-29.29; P = 0.011). CONCLUSION: Heterogeneous enhancement detected by MDCT immediately after primary PCI may provide promising information for predicting MVO and LV remodelling in patients with AMI.

Efficacy of Endeavor zotarolimus-eluting stent implantation for the treatment of very late stent thrombosis with late-acquired incomplete stent apposition after sirolimus-eluting stent implantation.

Very late stent thrombosis (VLST) is a serious complication after percutaneous coronary intervention. However, the best therapy for VLST with late-acquired incomplete stent apposition and incomplete neointimal coverage remains unknown. In these cases, neointimal coverage was nearly complete and no late-acquired malapposition was detected at 18 months after Endeavor zotarolimus-eluting stent (ZES) implantation for the treatment of VLST with late-acquired incomplete stent apposition after sirolimus-eluting stent implantation. We presented that Endeavor ZES implantation may become an attractive therapeutic strategy for the treatment of VLST with late-acquired incomplete stent apposition and incomplete neointimal coverage.

Clinical predictors of contrast-induced acute kidney injury in patients undergoing emergency versus elective percutaneous coronary intervention.

BACKGROUND: To evaluate the incidence and clinical predictors of contrast-induced acute kidney injury (CI-AKI) in patients with ST-segment elevation myocardial infarction (STEMI), unstable angina pectoris/non-STEMI (UAP/NSTEMI), and stable AP (SAP) undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: We enrolled 1,954 patients (SAP, n=1,222; UAP/NSTEMI, n=277; STEMI, n=455) who underwent PCI. Patients were categorized according to contrast media volume/estimated glomerular filtration rate ratio (CV/eGFR low: <2.0, mid: 2.0-2.9, high: ≥3.0). CI-AKI was defined as an increase in serum creatinine of 0.5mg/dl or 25% within 1 week from contrast-medium injection. The incidence of CI-AKI was highest among the STEMI patients (SAP, 4.24%; UAP/NSTEMI, 10.7%; STEMI, 16.1%, P<0.01). Significant predictors of CI-AKI were emergency PCI (odds ratio [OR] 3.70; 95% confidence interval [CI] 2.55-5.37; P<0.001), ejection fraction <40% (OR 2.04; 95% CI 1.24-3.36; P=0.005), and hemoglobin <10g/dl (OR 0.02; 95% CI 1.17-4.55; P=0.02) after multivariate logistic regression analysis. In the SAP group, a CV/eGFR ratio ≥3.0 was a significant predictor of CI-AKI (P=0.048), but not in UAP/NSTEMI and STEMI patients. CONCLUSIONS: UAP/NSTEMI and STEMI patients undergoing emergency PCI were at high risk for CI-AKI regardless of CV/eGFR ratio. Minimizing the dose of contrast medium based on eGFR might be valuable in reducing the risk of CI-AKI in SAP patients.

Dislodged and mechanically distorted stent stuck within a previously implanted drug-eluting stent.

Coronary stent loss during percutaneous coronary intervention is rare and is often associated with significant morbidity. Several retrieval techniques, overlying stent deployment and crushing, and surgical removal can be used to deal with a stent lost in the coronary system. We successfully treated a dislodged and mechanically distorted coil stent stuck within a previously implanted drug-eluting stent (DES) by stent-crush technique. This case might provide insight into the mechanisms responsible for the longitudinal fragility of cobalt alloy and coil-structure stents and stent fracture of DES. In the DES era, careful attention should be paid to such complications when attempting to deliver a stent to a distal vessel through a pre-existing DES.

Emergency transcatheter aortic valve implantation with a self-expandable valve under extracorporeal membrane oxygenation for cardiogenic shock due to bicuspid aortic stenosis: a case report.

Background: Transcatheter aortic valve implantation (TAVI) is an established treatment for patients with severe aortic stenosis (AS). However, the effectiveness of TAVI for patients with cardiogenic shock due to severe bicuspid AS, who require mechanical circulatory support, needs further investigation. Case summary: A 64-year-old male patient was admitted to the hospital with congestive heart failure secondary to severe AS and severe left ventricular dysfunction. After admission, he developed cardiogenic shock, further worsening his condition. The patient was placed on veno-arterial extracorporeal membrane oxygenation support and an intra-aortic balloon pump and transferred to our hospital. Cardiac computed tomography revealed a severely calcified type 1 bicuspid valve. The patient was deemed inoperable by our heart team. Therefore, an emergency transfemoral TAVI with a self-expandable valve was performed on Day 2. It significantly improved his haemodynamic stability. The patient was finally discharged on Day 29 without any neurological sequelae. Discussion: Cardiogenic shock due to severe AS has poor prognosis. However, this case report demonstrates that TAVI could be the optimal treatment for haemodynamically unstable patients with severe AS who require mechanical circulatory support.

Instant subacute stent thrombosis after maximum-load cardiopulmonary exercise test in a clopidogrel poor metabolizer with acute coronary syndrome.

A 63-year-old man with a hobby of full marathon and triathlon fainted while commuting on a 25-km one-way bicycle trip and was admitted to the hospital after return of spontaneous circulation. The patient was diagnosed with acute coronary syndrome, and contrast-enhanced computed tomography for trauma diagnosis indicated suspicion of liver injury. Although coronary angiography revealed a severe stenotic lesion in the left anterior descending artery, percutaneous coronary intervention (PCI) was deferred because of thrombolysis in myocardial infarction grade 3 flow. Following neurological recovery, the patient was started on dual antiplatelet therapy (aspirin and clopidogrel). On day 11, a 3.0/34-mm Resolute Onyx stent (Medtronic, Dublin, Ireland) was deployed following rotablation. As a pre-discharge evaluation, a maximum-load cardiopulmonary exercise test was performed 8 days after PCI. However, the patient developed stent thrombosis after 2 h. Subsequently, the patient was diagnosed as a clopidogrel poor metabolizer using a blood test. Learning objective: Existing guidelines recommend a cardiopulmonary exercise test (CPET) before or immediately after the discharge of patients with acute coronary syndrome (ACS). However, the safety of the maximum-load CPET has not been established, especially in clopidogrel poor metabolizers with ACS. Acute maximal exercise induces platelet aggregation; therefore, further discussion is needed regarding the timing of CPET, exercise load level, and patient observation post-CPET in ACS patients after stent placement.

Subendocardial Ischemia Caused by Acute Severe Aortic Regurgitation Due to Aortic Root Dissection: A Case Report and Literature Review.

Electrocardiogram (ECG) findings showing ST-segment depression in a wide range of leads and ST-segment elevation in aVR are found in patients with acute coronary syndrome with multivessel coronary lesions and left main trunk lesions. A 64-year-old man with a history of eosinophilic granulomatosis presented with chest pain and dyspnea. Although an ECG showed the above findings, he was diagnosed with acute severe aortic regurgitation (AR) complicating aortic root dissection and successfully underwent urgent Bentall operation. These ECG findings indicated that acute severe AR caused subendocardial ischemia.

Prevention of Contrast-Induced Nephropathy After Emergency Percutaneous Coronary Intervention With a Single Bolus Administration of High-Concentrate Sodium Bicarbonate　- Rationale and Design of a Single-Arm Study Compared With Historical Controls.

Background: Contrast-induced nephropathy (CIN) is clinically important because of its poor prognosis. The incidence of CIN is higher in emergency than elective percutaneous coronary intervention (PCI) because there is no established method to prevent CIN. The aim of this study is to evaluate whether bolus administration of a concentrated solution of sodium bicarbonate can prevent CIN in patients undergoing emergency PCI. Methods and Results: This multicenter prospective single-arm trial with historical controls will include patients who are aged ≥20 years and will undergo cardiac catheterization for suspected acute myocardial infarction (AMI). Patients will receive an intravenous bolus administration of concentrated sodium bicarbonate solution (7% or 8.4%, 20 mEq) and will be observed for 72±12 h. Data for the control group, comprising all patients who underwent PCI for AMI between January 1, 2020 and December 31, 2020 across participating hospitals, will be extracted. The primary endpoint is the incidence of CIN, defined as an increase in serum creatinine of >0.5 mg/dL or >25% from baseline within 48±12 h. We will evaluate the endpoints in the prospective group and compare them with those in the historical control group. Conclusions: This study will evaluate whether a single bolus administration of concentrated sodium bicarbonate can prevent CIN after emergency PCI.

Effect of individual proton pump inhibitors on cardiovascular events in patients treated with clopidogrel following coronary stenting: results from the Ibaraki Cardiac Assessment Study Registry.

OBJECTIVES: The aim of this study was to evaluate whether combination therapy of clopidogrel and proton pump inhibitors (PPIs) causes higher numbers of cardiovascular events than clopidogrel alone in Japanese patients. BACKGROUND: PPIs are often prescribed in combination with clopidogrel following coronary stenting. PPIs are reported to diminish the effect of clopidogrel because both are metabolized by CYP2C19. However, no reports address the effects of PPIs on cardiovascular events following coronary stenting in the Japanese population. METHODS: A total of 1,887 patients treated with clopidogrel following coronary stenting were enrolled in the Ibaraki Cardiac Assessment Study (ICAS) registry. All subjects were classified into two groups according to treatment without (n = 819) or with (n = 1,068) PPI. Propensity score analysis matched 1:1 according to treatment without PPI (n = 500) or with PPI (n = 500). Primary endpoint was the composite of all-cause death or myocardial infarction. RESULTS: No significant difference was observed in the primary endpoint between the group without PPI and the group with PPI (4.6% vs. 4.6%, P = 0.77). In contrast, a significant difference was found between the group without PPI and with PPI in regard to the incidence of gastrointestinal bleeding at the end of the follow-up period and the specific PPI prescribed (2.4% vs. 0.8%, adjusted HR = 0.30, 95% Confidence interval 0.08-0.87, P = 0.026) after propensity score matching. CONCLUSIONS: No significant association between PPI use and primary endpoint was observed in the Japanese population, whereas PPI use resulted in a significant reduction in the rate of gastrointestinal bleeding.