Acute Left Main Coronary Embolization Following Transcatheter Aortic Valve Implantation.

Acute coronary occlusion just after transcatheter aortic valve implantation (TAVI) is a rare but fatal complication, with an incidence of less than 1% but a 30-day mortality rate of up to 50%. The most likely mechanism of acute coronary occlusion following TAVI is the obstruction by the native aortic valve leaflet. However, acute coronary occlusion due to embolus has been rarely reported, and we herein report the case. An 80-year-old woman with severe aortic stenosis and chronic myelogenous leukemia (CML) underwent transfemoral TAVI with a 23-mm balloon-expandable valve. Just before leaving an operation room about 30 minutes after the TAVI procedure, she went into cardiopulmonary arrest. Emergent coronary angiography showed the occlusion of the middle to the distal left main coronary artery with a large embolus. Percutaneous coronary intervention (PCI) was immediately performed, and a drug-eluting stent was eventually placed to improve good coronary flow. She was finally discharged on foot without any other complications and was doing well one year after TAVI with normal left ventricular systolic function and no in-stent restenosis. Considering the transthoracic echocardiography before TAVI and the intravascular ultrasound findings during PCI, it was most likely thought to be caused by the embolus of the degenerated aortic valve tissue. In conclusion, although acute coronary occlusion by embolization following the TAVI procedure is exceedingly rare, we could successfully rescue the patient with immediate PCI.

Localized Pulmonary Edema Secondary to Pulmonary Embolism.

A 47-year-old man had localized pulmonary edema (LPE) and a massive pulmonary embolism. The cause of LPE was believed to be a high blood supply to the spared pulmonary artery territories without a thrombus. The patient was successfully treated with unfractionated heparin and thrombolytic agents.

Risk stratification and prognosis prediction using cardiac biomarkers in COVID-19: a single-centre retrospective cohort study.

OBJECTIVE: There is a need for a robust tool to stratify the patient's risk with COVID-19. We assessed the prognostic values of cardiac biomarkers for COVID-19 patients. METHODS: This is a single-centre retrospective cohort study. Consecutive laboratory-confirmed COVID-19 patients admitted to the Kobe City Medical Center General Hospital from July 2020 to September 2021 were included. We obtained cardiac biomarker values from electronic health records and institutional blood banks. We stratified patients with cardiac biomarkers as high-sensitive troponin I (hsTnI), N-terminal pro-B-type natriuretic peptide (NT-proBNP), creatine kinase (CK) and CK myocardial band (CK-MB), using the clinically relevant thresholds. Prespecified primary outcome measure was all-cause death. RESULTS: A total of 917 patients were included. hsTnI, NT-proBNP, CK and CK-MB were associated with the significantly higher cumulative 30-day incidence of all-cause death (hsTnI: <5.0 ng/L group; 4.3%, 5.0 ng/L-99%ile upper reference limit (URL) group; 8.8% and ≥99% ile URL group; 25.2%, p<0.001. NT-proBNP: <125 pg/mL group; 5.3%, 125-900 pg/mL group; 10.5% and ≥900 pg/mL group; 31.9%, p<0.001. CK:

Association of HFA-PEFF score with clinical outcomes after catheter ablation for atrial fibrillation.

BACKGROUND: The Heart Failure Association Pretest assessment, echocardiography and natriuretic peptide, functional testing and final aetiology (HFA-PEFF) score has been developed for diagnosing heart failure with preserved ejection fraction (HFpEF), which is frequently associated with atrial fibrillation (AF). We aimed to investigate whether preprocedural HFA-PEFF score could be used to predict clinical outcomes in patients with AF who underwent catheter ablation (CA). METHODS: Overall, 1679 patients with AF who underwent primary CA (71±10 years, 1218 males (72.5%), median follow-up duration 3.3 years) from July 2011 to December 2019 were included in this retrospective study. HFpEF was defined as an HFA-PEFF score ≥5. The primary study outcome was 5-year major adverse cardiovascular and cerebrovascular events (MACCE), which is a composite of all-cause death, hospitalisation for heart failure (HF) and hospitalisation for stroke. RESULTS: The prevalence of HFpEF was 32.3%, but only 7.7% were diagnosed with HF at the time of CHADS2 scoring. Five-year MACCE occurred in 77 patients (4.6%). The cumulative 5-year incidence of MACCE was significantly higher in the HFpEF group than in the non-HFpEF group (11.2% vs 4.8% at 5 years, p<0.001). In the multivariable analysis, HFpEF by the HFA-PEFF score was associated with MACCE (adjusted HR 1.65, 95% CI 1.02 to 2.65, p=0.041). CONCLUSIONS: Early detection of HFpEF using the HFA-PEFF score may have clinical applications in guiding therapeutic decision-making and improving prognosis by preventing HF and stroke in patients with AF undergoing CA.

Statin Discontinuation After Coronary Revascularization.

There is a scarcity of studies evaluating statin discontinuation in patients with coronary artery disease in real-world practice. In 11,144 patients who underwent first coronary revascularization and taking statins in the CREDO-Kyoto Registry Cohort-3, we evaluated the incidence of statin discontinuation, defined as stopping statins for at least 2 months. The reasons for statin discontinuation included nonadherence, side effects, worsening co-morbidities, surgery, prescription error, and direction by physicians for other reasons. During a median 6 years of follow-up, the cumulative incidence of statin discontinuation was 6.1% at 1 year, 12.4% at 3 years, 17.4% at 5 years, and 21.4% at 7 years. The major components of the reasons for statin discontinuation were nonadherence, side effects, and worsening co-morbidities. Compared with patients with statin discontinuation because of other reasons, patients with statin discontinuation because of nonadherence more often had younger age, men, acute coronary syndrome, and current smoking; patients with statin discontinuation because of side effects more often had liver cirrhosis; and patients with statin discontinuation because of worsening co-morbidities more often had advanced age and co-morbidities such as malignancy. Statin discontinuation was strongly associated with subsequent mortality (hazard ratio [HR] 3.54; 95% confidence interval [CI] 3.18 to 3.94, p <0.001), which was consistent, regardless of the reasons, except for the small group of patients with prescription error (nonadherence: HR 2.35, 95% CI 1.69 to 3.27, p <0.001; side effects: HR 2.48, 95% CI 1.84 to 3.34, p <0.001; worsening co-morbidities: HR 22.08, 95% CI 18.55 to 26.29, p <0.001). In conclusion, in real-world practice, approximately 1 in 5 patients discontinued statins after coronary revascularization during a median of 6 years of follow-up. Statin discontinuation was associated with subsequent mortality.

Single-Session Versus Staged Multivessel Optimal IVUS-Guided PCI in Patients With CCS or NSTE-ACS.

Background: There are no studies comparing single-session vs staged multivessel intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) in patients with chronic coronary syndrome (CCS) or non-ST-segment-elevation acute coronary syndrome (NSTE-ACS). Objectives: The authors aimed to compare single-session vs staged multivessel IVUS-guided PCI in patients with CCS or NSTE-ACS. Methods: The OPTIVUS-Complex PCI study multivessel cohort was a prospective multicenter single-arm trial enrolling 1,021 patients with CCS or NSTE-ACS undergoing multivessel PCI including left anterior descending coronary artery using IVUS aiming to meet the prespecified OPTIVUS criteria for optimal stent expansion. We compared single-session vs staged multivessel PCI. The primary endpoint was a composite of death, myocardial infarction, stroke, or any coronary revascularization. Results: There were 246 patients (24.1%) undergoing single-session multivessel PCI, and 775 patients (75.9%) undergoing staged multivessel PCI. There was a wide variation in the prevalence of single-session multivessel PCI across the participating centers. The staged multivessel PCI group more often had complex coronary anatomy such as 3-vessel disease, chronic total occlusion, and calcified lesions requiring an atherectomy device compared with the single-session multivessel PCI group. The rates of PCI success, procedural complications, and meeting OPTIVUS criteria were not different between groups. The cumulative 1-year incidence of the primary endpoint was not different between single-session and staged multivessel PCI groups (9.0% vs 10.8%, log-rank P = 0.42). After adjusting confounders, the effect of single-session multivessel PCI relative to staged multivessel PCI was not significant for the primary endpoint (HR: 0.95; 95% CI: 0.58-1.55; P = 0.84). Conclusions: Single-session and staged multivessel IVUS-guided PCI had similar 1-year outcomes.

Importance of the relative epicardial connection locations and right-sided pulmonary vein isolation line for successful pulmonary vein isolation.

INTRODUCTION: The presence of an epicardial connection (EC) decreases the success rate of pulmonary vein isolation (PVI); however, the effect of designing isolation lines has not been evaluated. We sought to clarify the effects of designing an anterior line for right-sided PVI considering the presence and location of the EC. METHODS: Seventy-four consecutive patients who underwent initial catheter ablation for atrial fibrillation were retrospectively included in this study. The presence of the EC was determined by the left atrial (LA) activation map during right atrial pacing, and patients were divided into EC-positive (n = 23, 31%) and EC-negative (n = 51, 69%) groups. EC-positive patients were further subdivided based on the EC location: on-the-line group, (EC on the PVI line, n = 11); inside-line group (EC on the pulmonary vein [PV] side, n = 10); and outside-line group (EC on the LA side, n = 2). The PVI parameters were compared among the three groups. RESULTS: The success rates of the first-pass isolation were comparable between the EC-negative and EC-positive groups (70.6% vs. 60.9%, ns), but the success rate was significantly higher in the on-the-line group than in the inside-line group (91% vs. 20%, p = 0.002). First-pass isolation was successful in both patients in the outside-line group. Additional carina ablation was required only in the inside-line group. CONCLUSIONS: The association between the EC site and the right-sided PV anterior isolation line affected the success rate of first-pass isolation. For successful right-sided PVI, it is important to consider the EC site when designing the PVI line.

Successful pregnancy and delivery in a young-onset hypertrophic cardiomyopathy patient with a novel doublet-base substitution in the MYH7 gene.

Herein, we report the case of a young-onset female hypertrophic cardiomyopathy (HCM) patient with severe left ventricular outflow tract obstruction who had a family history of premature sudden cardiac death. Despite the severe HCM phenotype, the patient was successfully managed by low-dose bisoprolol during two peripartum periods after a percutaneous transluminal septal myocardial ablation.We performed whole-genome sequencing analysis and found a novel doublet-base substitution (DBS) in the MYH7 gene (c.2608_2609delinsTT, p.R870F) in this patient. Her children were also genetically tested after careful genetic counselling to their parents, and one of her children at 1-year-old with left ventricular hypertrophy was found to have the same gene mutation. The location of the DBS in a functionally important domain and the inheritance of the same mutation in the offspring with the HCM phenotype suggested that this mutation in the MYH7 gene was responsible for the severe HCM phenotype. Proactive genetic testing would provide beneficial information for appropriate follow-up and initiation of therapy in children with possibly pathogenic gene mutations; however, revisions of genetic counselling may be considered according to their growth. Learning objective: Hypertrophic cardiomyopathy (HCM) patients with severe left ventricular outflow tract obstruction are at a high risk of hemodynamic deterioration during pregnancy. Preceding myocardial ablation therapy and a careful medical management during peripartum period may enable safe pregnancy and delivery in severe obstructive HCM patients. A novel doublet-base substitution in the MYH7 gene (c.2608_2609delinsTT, p.R870F) was found as a likely pathogenic mutation of young-onset severe HCM.

Long-Term Clinical Outcomes in Patients With Severe Tricuspid Regurgitation.

Background The natural history and optimal interventional timing in patients with isolated severe tricuspid regurgitation (TR) have not been well studied. This study aimed to investigate long-term clinical outcomes and risk factors associated with poor prognosis in patients with isolated severe TR. Methods and Results Consecutive transthoracic echocardiographic examinations in 2877 patients with isolated severe TR were retrospectively reviewed. Patients with significant left-sided valve disease or repeated examinations were excluded. Primary outcome was defined as a composite of all-cause death and hospitalization for heart failure. Among the 613 enrolled patients (mean age, 74±13 years; men, 38%), 141 died, and 62 were hospitalized for heart failure during the median follow-up period of 26.5 (interquartile range, 6.0-57.9) months. The 5-year event-free rate was 60.1%. TR pressure gradient (adjusted hazard ratio [HR], 1.03 [95% CI, 1.01-1.04]), blood urea nitrogen (adjusted HR, 1.02 [95% CI, 1.01-1.04]), left atrial volume index (adjusted HR, 1.01 [95% CI, 1.002-1.02]), and serum albumin (adjusted HR, 0.56 [95% CI, 0.36-0.95]) were identified as independent predictors of adverse events. A risk model based on the 4 clinical factors that included pulmonary hypertension (TR pressure gradient >40 mm Hg), elevated blood urea nitrogen levels (>25 mg/dL), decreased albumin levels (<3.7 g/dL), and left atrial enlargement (left atrial volume index <34 mL/m2) revealed a graded increase in the risk of adverse events (P<0.001). Conclusions The prognosis of isolated severe TR is not always favorable. Careful attention should be paid to patients with concomitant risk factors, such as pulmonary hypertension, elevated blood urea nitrogen levels, decreased albumin levels, and left atrial enlargement.

Sex Differences in Clinical Outcomes After Percutaneous Coronary Intervention.

BACKGROUND: There is a scarcity of studies comparing the clinical outcomes after percutaneous coronary intervention (PCI) for women and men stratified by the presentation of acute coronary syndromes (ACS) or stable coronary artery disease (CAD).Methods and Results: The study population included 26,316 patients who underwent PCI (ACS: n=11,119, stable CAD: n=15,197) from the CREDO-Kyoto PCI/CABG registry Cohort-2 and Cohort-3. The primary outcome was all-cause death. Among patients with ACS, women as compared with men were much older. Among patients with stable CAD, women were also older than men, but with smaller difference. The cumulative 5-year incidence of all-cause death was significantly higher in women than in men in the ACS group (26.2% and 17.9%, log rank P<0.001). In contrast, it was significantly lower in women than in men in the stable CAD group (14.2% and 15.8%, log rank P=0.005). After adjusting confounders, women as compared with men were associated with significantly lower long-term mortality risk with stable CAD but not with ACS (hazard ratio [HR]: 0.75, 95% confidence interval [CI]: 0.69-0.82, P<0.001, and HR: 0.92, 95% CI: 0.84-1.01, P=0.07, respectively). There was a significant interaction between the clinical presentation and the mortality risk of women relative to men (interaction P=0.002). CONCLUSIONS: Compared with men, women had significantly lower adjusted mortality risk after PCI among patients with stable CAD, but not among those with ACS.

Low-Density Lipoprotein Cholesterol Levels on Statins and Cardiovascular Event Risk in Stable Coronary Artery Disease　- An Observation From the REAL-CAD Study.

BACKGROUND: The relationship between very low on-treatment low-density lipoprotein cholesterol (LDL-C) level and cardiovascular event risk is still unclear in patients receiving the same doses of statins.Methods and Results: From the REAL-CAD study comparing high-dose (4 mg/day) with low-dose (1 mg/day) pitavastatin therapy in patients with stable coronary artery disease, 11,105 patients with acceptable statin adherence were divided into 3 groups according to the on-treatment LDL-C level at 6 months (<70 mg/dL, 70-100 mg/dL, and ≥100 mg/dL). The primary outcome measure was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, or unstable angina requiring emergent admission. The adjusted risks of the LDL-C <70 mg/dL group relative to the LDL-C 70-100 mg/dL group (reference) was not significantly different for the primary outcome measure in both 1 mg/day and 4 mg/day strata (HR 0.84, 95% CI 0.58-1.18, P=0.32, and HR 1.25, 95% CI 0.88-1.79, P=0.22). The adjusted risk of the LDL-C ≥100 mg/dL group relative to the reference group was not significant for the primary outcome measure in the 1 mg/day stratum (HR 0.82, 95% CI 0.60-1.11, P=0.21), whereas it was highly significant in the 4 mg/day stratum (HR 3.32, 95% CI 2.08-5.17, P<0.001). CONCLUSIONS: A very low on-treatment LDL-C level (<70 mg/dL) was not associated with lower cardiovascular event risk compared with moderately low on-treatment LDL-C level (70-100 mg/dL) in patients receiving the same doses of statins.

Diagnostic Accuracy of the 2016 Guideline-Based Echocardiographic Algorithm to Estimate Invasively-Measured Left Atrial Pressure by Direct Atrial Cannulation.

BACKGROUND: Although estimation of left ventricular filling pressure (LVFP) using an integrated echocardiographic algorithm is recommended, the usefulness of this algorithm has not been fully validated. OBJECTIVES: The purpose of this study was to investigate the reliability of an algorithmic classification system using invasively measured left atrial pressure (LAP) in a large-scale cohort. METHODS: The authors enrolled 1,967 patients (age 68 ± 10 years) whose LAP was directly measured within the left atrium during catheter ablation for atrial fibrillation. Patients were classified into 3 groups based on the echocardiographic algorithm: normal (group N, n = 1,282), undetermined (group U, n = 160), and elevated (group E, n = 346) LAP groups. Invasively measured LAP and echocardiographic parameters estimating LVFP were compared among the groups. RESULTS: The median LAP was 12.6 ± 5.7 mm Hg in the entire cohort. LAP was significantly higher in group E than that in the other groups (groups E vs U vs N, 14.2 ± 6.3 mm Hg vs 13.5 ± 5.9 mm Hg vs 12.0 ± 5.5 mm Hg; P < 0.001). Among group E patients, 43.1% had elevated LAP (≥15 mm Hg), whereas 56.9% had normal LAP (<15 mm Hg). Of the patients in group N, 69.0% had normal LAP, whereas 31% had elevated LAP. Although the correlation between invasively measured LAP and E/e', peak tricuspid regurgitant velocity, and left atrial volume index was modest, the number of abnormal values correlated significantly with elevated LAP (P < 0.001). CONCLUSIONS: The classification using combined echocardiographic parameters in the recommendations may be useful for detecting patients with normal LVFP but may be limited for detecting elevated LVFP.

Central and Enteric Neuroprotective Effects by Eucommia ulmoides Extracts on Neurodegeneration in Rotenone-induced Parkinsonian Mouse.

Parkinson's disease (PD) is a progressive neurodegenerative disease of both the central and peripheral / enteric nervous systems. Oxidative stress and neuroinflammation are associated with the pathogenesis of PD, suggesting that anti-oxidative and anti-inflammatory compounds could be neuroprotective agents for PD. Eucommia ulmoides (EU) is a traditional herbal medicine which exerts neuroprotective effects by anti-inflammatory and anti-oxidative properties. Our previous study showed that treatment with chlorogenic acid, a component of EU, protected against neurodegeneration in the central and enteric nervous systems in a PD model. In this study, we examined the effects of EU extract (EUE) administration on dopaminergic neurodegeneration, glial response and α-synuclein expression in the substantia nigra pars compacta (SNpc), and intestinal enteric neurodegeneration in low-dose rotenone-induced PD model mice. Daily oral administration of EUE ameliorated dopaminergic neurodegeneration and α-synuclein accumulation in the SNpc. EUE treatment inhibited rotenone-induced decreases in the number of total astrocytes and in those expressing the antioxidant molecule metallothionein. EUE also prevented rotenone-induced microglial activation. Furthermore, EUE treatment exerted protective effects against intestinal neuronal loss in the PD model. These results suggest that EU exerts neuroprotective effects in the central and enteric nervous systems of rotenone-induced parkinsonism mice, in part by glial modification.

Effectiveness of a manual dragging laser irradiation technique using the first-generation endoscopic laser balloon ablation system for pulmonary vein isolation.

Background: Although high efficacy of laser balloon (LB) ablation for atrial fibrillation (AF) has been shown, the conventional point-by-point technique requires a long procedure time. We investigated the clinical effectiveness of the manual dragging laser technique. Methods: We enrolled 51 consecutive patients with paroxysmal AF who underwent pulmonary vein isolation (PVI) using first-generation LB (LB1) at our institution. The first 25 patients underwent PVI using a point-by-point laser irradiation maneuver (point-by-point group). The latter 26 patients underwent PVI using a manually dragging laser irradiation maneuver (dragging group). The power and delivery time for the laser energy were selected from a preset protocol with 5.5-12 W and 20-30 s for each application. The dragging irradiation method was performed by manually rotating approximately 1.5°/s during one irradiation application. Results: PVI was successful in all cases. The duration of PVI was shorter (66 ± 20 vs. 116 ± 39 min, p < 0.0001), and the number of laser irradiations for the 4PVs were significantly less in the dragging group. There were four recurrent cases (16%) in the point-by-point group and 1 (4%) in the dragging group. There was no significant difference in the survival rate free from recurrence after the blanking period between the two groups (log-rank p = 0.1570). The complications were similar between the groups (4% vs. 4%, ns). Conclusions: The manual dragging laser irradiation technique using LB1 could shorten the PVI procedure time while preserving clinical effectiveness.

Comparison of Cryoballoon and Contact Force-Sensing Radiofrequency Ablation for Persistent Atrial Fibrillation in Clinical Practice.

BACKGROUND: Outcomes of cryoballoon ablation for persistent atrial fibrillation (AF) are unclear, especially in Japanese patients, so the effectiveness and safety of cryoballoon ablation in clinical practice were retrospectively compared with those of contact force-sensing radiofrequency (CFRF) ablation including the high-power protocol.Methods and Results:Consecutive patients with persistent AF were reviewed, and 253 and 265 patients who underwent cryoballoon and CFRF ablation, respectively, were enrolled. The primary endpoint was atrial arrhythmia recurrence. The secondary endpoints were periprocedural complications and repeat ablation. The rate of additional left atrial (LA) ablation after pulmonary vein isolation (PVI) was similar between groups (68.8% cryoballoon vs. 74.0% CFRF, P=0.19). Freedom from atrial arrhythmia recurrence was comparable between groups over a follow-up of 25.5±12.5 months (72.3% cryoballoon vs. 69.8% CFRF; adjusted hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.59-1.21, P=0.36). Outcomes were similar in the subgroups of PVI alone and PVI plus additional LA ablation. LA posterior wall isolation, absence of defragmentation, and low creatine clearance, but not catheter selection, were associated with the primary endpoint. Periprocedural complications (adjusted HR 0.73, 95% CI 0.34-1.54, P=0.41) and repeat ablation (adjusted HR 1.11, 95% CI 0.71-1.74, P=0.64) were similar for both procedures. CONCLUSIONS: Cryoballoon ablation for persistent AF in Japanese clinical practice had acceptable outcomes comparable to those of advanced CFRF ablation.

Early experiences with three types of balloon-based ablation catheters in patients with paroxysmal atrial fibrillation.

BACKGROUND: Although balloon-based ablation catheters are expected to improve the feasibility and quality of pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF), they must be introduced to physicians in the proper setting to ensure their correct usage. OBJECTIVE: To identify the optimal clinical settings for learning the techniques for 3 balloon-based ablation catheters (Cryoballoon, Hotballoon, and Laserballoon). METHODS: We introduced 3 balloon catheters in 50 consecutive patients with paroxysmal AF each during the introduction periods. Clinical parameters were compared among the groups and between these groups and their steady-state controls. RESULTS: The completion rate of PVI by sole balloon procedures was 56% with the Hotballoon catheter, which was lower than those of the Cryoballoon and Laserballoon catheters (each 88%). Radiofrequency touch-up was most frequently required at the bottom aspect of the inferior pulmonary veins (PVs) in the Cryoballoon group and at the anterior aspect of the superior PVs in the Hotballoon and Laserballoon groups. The Laserballoon catheter had the longest average PVI procedural time (89.2 ± 40 vs 58.4 ± 22 minutes for Hotballoon, 65.1 ± 25 minutes for Cryoballoon, P < .001), but the difference was ultimately removed by the learning curve. There was no significant difference in the major complication or recurrence-free survival rates among the catheter types. CONCLUSIONS: All 3 balloon-based catheter types allowed feasibility and quality for PVI, even during the learning period. To introduce these new catheters without complications, an experiences of 20 cases with specific clinical settings should be met for each catheter type.

Details on the effect of very short dual antiplatelet therapy after drug-eluting stent implantation in patients with high bleeding risk: insight from the STOPDAPT-2 trial.

Previously we briefly reported the effect of 1-month dual antiplatelet therapy (DAPT) for patients with high bleeding risk (HBR) receiving percutaneous coronary intervention (PCI) in the STOPDAPT-2 trial, but full analysis data have not been available. We conducted post hoc subgroup analysis regarding the effect of very short DAPT for HBR patients in STOPDAPT-2 trial. The primary endpoint was a 1-year composite of cardiovascular (cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke) and bleeding (TIMI major/minor bleeding) outcomes. Major secondary endpoints were 1-year cardiovascular composite endpoint and bleeding endpoint. HBR was defined by the academic research consortium (ARC) HBR criteria. Among the 3009 study patients, 1054 (35.0%) were classified as HBR and 1955 (65.0%) were as non-HBR. There were no significant interactions between HBR/non-HBR subgroups and the assigned DAPT group on the primary endpoint (HBR; 3.48% vs. 5.98%, HR 0.57, 95% CI 0.32-1.03, and non-HBR; 1.81% vs. 2.36%, HR 0.78, 95% CI 0.42-1.45; P for interaction = 0.48), the major secondary cardiovascular endpoint (HBR; 3.07% vs. 4.03%, HR 0.77, 95% CI 0.40-1.48, and non-HBR; 1.41% vs. 1.61%, HR 0.89, 95% CI 0.43-1.84; P for interaction = 0.77), and the major secondary bleeding endpoint (HBR; 0.41% vs. 2.71%, HR 0.15, 95% CI 0.03-0.65, and non-HBR; 0.40% vs. 0.85%, HR 0.48, 95% CI 0.14-1.58; P for interaction = 0.22). In conclusion, the effects of 1-month DAPT for the primary and major secondary endpoints were consistent in HBR and non-HBR patients without any significant interactions. The benefit of 1-month DAPT in reducing major bleeding was numerically greater in HBR patients.Clinical trial registration Short and optimal duration of dual antiplatelet therapy after everolimus-eluting cobalt-chromium stent-2 [STOPDAPT-2]; NCT02619760.

Outcomes and predictors of cardiac events in medically treated patients with atrial functional mitral regurgitation.

BACKGROUND: Little is known about the outcomes and predictors of adverse cardiac events in medically treated patients with atrial functional mitral regurgitation (FMR). METHODS: We screened 1405 consecutive patients with grade ≥ 3+ mitral regurgitation (MR) detected by echocardiography. After excluding patients with previous or early (within 3 months from diagnosis) mitral valve surgery, congenital heart disease, hypertrophic cardiomyopathy, severe aortic valve disease, or unknown etiology, the study population consisted of 319 patients with primary MR, 395 patients with FMR with left ventricular (LV) dysfunction, and 184 patients with atrial FMR. Atrial FMR was defined as FMR in patients without LV wall motion abnormality or dilatation. RESULTS: The cumulative incidence of the composite of cardiac death and heart failure hospitalization at 3 years was 10.5% in primary MR, 37.5% in FMR with LV dysfunction, and 14.0% in atrial FMR (p < .001). In atrial FMR patients, LV end-diastolic volume index (hazard ratio [HR] 1.06, 95% confidence interval [CI] 1.02-1.10), severe MR (grade 4+) (HR 2.73, 95% CI 1.21-6.12), being symptomatic (NYHA ≥ 2) (HR 2.82, 95% CI 1.15-6.92), and having ≥1 comorbidities (HR 3.96, 95% CI 1.74-9.00) were independently associated with an increased risk for adverse cardiac events by a multivariable Cox regression analysis. CONCLUSIONS: Outcomes of medically treated patients with atrial FMR were better than those of FMR with LV dysfunction, but worse than those of primary MR. In atrial FMR patients, LV dilatation, severe MR, being symptomatic, and the presence of comorbidities were independently associated with an increased risk for adverse cardiac events.

More- Versus Less-Intensive Lipid-Lowering Therapy.

BACKGROUND: It has not been yet adequately addressed whether the addition of the nonstatin LDL-C (low-density lipoprotein cholesterol)-lowering agents on top of statins has the same magnitude of risk reduction in the cardiovascular events as compared with more-intensive statin therapy. METHODS AND RESULTS: We performed a systematic review and meta-analysis of RCTs (randomized controlled trials) comparing more- versus less-intensive lipid-lowering therapy (LLT) on clinical outcomes in patients with atherosclerotic cardiovascular risk. We included 23 studies involving 133 037 patients (more-intensive LLT: 67 691 patients and less-intensive LLT: 65 346 patients). We evaluated 3 types of more- versus less-intensive LLT including more versus less statins (57 672 patients), combination therapy of ezetimibe versus statins alone (20 688 patients), or a PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitor with statins versus statins alone (54 677 patients). The odds for major adverse cardiovascular events (MACE; equivalent to the composite of coronary heart death, nonfatal myocardial infarction, stroke, or coronary revascularization) were significantly lower in the more-intensive LLT group compared with the less-intensive LLT group in the entire study population (odds ratio, 0.84; 95% CI, 0.79-0.88; P<0.001), and in all the 3 categories of more-intensive LLT strategies (more-intensive statin therapy: odds ratio, 0.83; 95% CI, 0.76-0.90; P<0.001, ezetimibe: odds ratio, 0.90; 95% CI, 0.85-0.96; P<0.001, and PCSK9 inhibitors: odds ratio, 0.81; 95% CI, 0.73-0.90; P<0.001) with numerically greater relative odds reduction by more-intensive statin therapy and PCSK9 inhibitors than by ezetimibe. Odds reduction for MACE per 20 mg/dL LDL-C reduction was also different across the 3 types of more-intensive LLT (more-intensive statin therapy: 17.4%, ezetimibe: 11.0%, and PCSK9 inhibitors: 6.6%). CONCLUSIONS: In this meta-analysis, more-intensive LLT as compared with less-intensive LLT was associated with significant odds reduction for MACE in the entire study population and in all the 3 categories of more-intensive LLT such as more-intensive statin therapy, ezetimibe, and PCSK9 inhibitors. However, overall odds reduction for MACE and odds reduction for MACE per 20 mg/dL LDL-C reduction were different across the 3 types of more-intensive LLT. Registration: URLs: https://www.crd.york.ac.uk/PROSPERO/ and http://www.umin.ac.jp/ctr. Unique identifiers: PROSPERO: CRD42018081196, and UMIN-CTR: R000036229.