The synthesis and structure of a C 3-symmetric propeller-shaped polycyclic aromatic hydrocarbon that bears three seven-membered rings is reported. The synthesis was accomplished in three steps from ...benzocnaphtho2,1-pchrysene, including a Pd-catalyzed intramolecular C–H arylation for the formation of the seven-membered rings. The combination of the helicities (P/M) of the three seven-membered-ring moieties and three 4helicene moieties affords 24 possible conformers, and two relatively stable conformations were observed by 1H NMR spectroscopy.
Background:There is a scarcity of data on short-duration dual antiplatelet therapy (DAPT) followed by P2Y12 inhibitor monotherapy as compared with aspirin monotherapy after percutaneous coronary ...intervention (PCI).Methods and Results:STOPDAPT-1 is a prospective trial enrolling patients who agreed to 3-month DAPT followed by aspirin monotherapy after everolimus-eluting stent (EES) implantation. STOPDAPT-2 is a randomized trial comparing 1-month DAPT followed by clopidogrel monotherapy with 12-month DAPT after EES implantation. We compared the clinical outcomes of patients assigned to the 1-month DAPT group in STOPDAPT-2 and the 3-month DAPT group enrolled in STOPDAPT-1. The current study population consisted of 1,480 patients in STOPDAPT-2 and 1,339 patients in STOPDAPT-1. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, definite stent thrombosis and TIMI major/minor bleeding. Cumulative 1-year incidence of the primary endpoint was not significantly different between STOPDAPT-2 and STOPDAPT-1 (2.3% vs. 2.3%, P=0.98). After adjusting for confounders, there was no excess risk of STOPDAPT-2 relative to STOPDAPT-1 for the primary endpoint. Between 3 and 12 months, the cumulative incidence of primary endpoint was not significantly different between STOPDAPT-2 and STOPDAPT-1 (1.7% vs. 1.6%, P=0.77).Conclusions:The effect of 1-month DAPT followed by clopidogrel monotherapy on clinical outcomes was similar to that of 3-month DAPT followed by aspirin monotherapy in patients receiving PCI.
Bleeding rates on dual antiplatelet therapy (DAPT) within 1 month after percutaneous coronary intervention (PCI) remain high in clinical practice, particularly in patients with acute coronary ...syndrome or high bleeding risk. Aspirin-free strategy might result in lower bleeding early after PCI without increasing cardiovascular events, but its efficacy and safety have not yet been proven in randomized trials.
We randomly assigned 6002 patients with acute coronary syndrome or high bleeding risk just before PCI either to prasugrel (3.75 mg/day) monotherapy or to DAPT with aspirin (81-100 mg/day) and prasugrel (3.75 mg/day) after loading of 20 mg of prasugrel in both groups. The coprimary end points were major bleeding (Bleeding Academic Research Consortium 3 or 5) for superiority and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke) for noninferiority with a relative 50% margin.
The full analysis set population consisted of 5966 patients (no-aspirin group, 2984 patients; DAPT group, 2982 patients; age, 71.6±11.7 years; men, 76.6%; acute coronary syndrome, 75.0%). Within 7 days before randomization, aspirin alone, aspirin with P2Y12 inhibitor, oral anticoagulants, and intravenous heparin infusion were given in 21.3%, 6.4%, 8.9%, and 24.5%, respectively. Adherence to the protocol-specified antiplatelet therapy was 88% in both groups at 1 month. At 1 month, the no-aspirin group was not superior to the DAPT group for the coprimary bleeding end point (4.47% and 4.71%; hazard ratio, 0.95 95% CI, 0.75-1.20;
=0.66). The no-aspirin group was noninferior to the DAPT group for the coprimary cardiovascular end point (4.12% and 3.69%; hazard ratio, 1.12 95% CI, 0.87-1.45;
=0.01). There was no difference in net adverse clinical outcomes and each component of coprimary cardiovascular end point. There was an excess of any unplanned coronary revascularization (1.05% and 0.57%; hazard ratio, 1.83 95%CI, 1.01-3.30) and subacute definite or probable stent thrombosis (0.58% and 0.17%; hazard ratio, 3.40 95% CI, 1.26-9.23) in the no-aspirin group compared with the DAPT group.
The aspirin-free strategy using low-dose prasugrel compared with the DAPT strategy failed to attest superiority for major bleeding within 1 month after PCI but was noninferior for cardiovascular events within 1 month after PCI. However, the aspirin-free strategy was associated with a signal suggesting an excess of coronary events.
URL: https://www.clinicaltrials.gov; Unique identifier: NCT04609111.
Background: The clinical features of heart failure (HF) in patients with hypertrophic cardiomyopathy (HCM) in Japan have not been fully elucidated.Methods and Results: In 293 patients with HCM ...(median age at registration, 65 (57–72) years) in a prospective cardiomyopathy registration network in Kochi Prefecture (Kochi RYOMA study), HF events (HF death or hospitalization for HF) occurred in 35 patients (11.9%) (median age, 76 (69–80) years), including 11 HF deaths during a median follow-up of 6.1 years. The 5-year HF events rate was 9.6%. Atrial fibrillation, low percentage of fractional shortening, and high B-type natriuretic peptide level at registration were predictors of HF events. The combination of these 3 factors had a relatively high positive predictive value (55%) for HF events and none of them had a high negative predictive value (99%). There were 4 types of HF profile: left ventricular (LV) systolic dysfunction (40%), severe LV diastolic dysfunction (34%), LV outflow tract obstruction (LVOTO) (20%), and primary mitral regurgitation (MR) (6%). HF deaths occurred in patients with LV systolic dysfunction or LV diastolic dysfunction, but none of patients with LVOTO or primary MR due to additional invasive therapies.Conclusions: In a Japanese HCM cohort, HF was an important complication, requiring careful follow-up and appropriate treatment.
Background:Data on the clinical outcomes of percutaneous coronary intervention (PCI) for unprotected left main coronary artery (LMCA) in patients with acute coronary syndrome (ACS) are limited. ...Therefore, this study aimed to assess the clinical outcome of patients with ACS who underwent PCI for LMCA culprit lesion.Methods and Results:Of 1,809 patients enrolled in the Assessing Optimal Percutaneous Coronary Intervention for the LMCA (AOI-LMCA) registry (a retrospective 6-center registry of consecutive patients undergoing LMCA stenting in Japan), the current study population consisited of 1,500 patients with unprotected LMCA stenting for LMCA ACS (ACS with shock: 115 patients, ACS without shock: 281 patients) and stable CAD (1,104 patients). The cumulative 180-day incidence of death was markedly higher in the ACS with shock group than in the other groups (49.5%, 8.6%, and 3.3%, respectively; P<0.0001), but mortality beyond 180-day was not significantly different among the 3 groups (30.2%, 20.4%, and 19.5%, respectively; P=0.65). In the ACS with shock group, the initial TIMI flow grade did not affect 5-year mortality (57.1% and 62.2%, P=0.99), but in the ACS without shock group, 5-year mortality was significantly higher in patients with initial TIMI flow grade ≤1 than in patients with TIMI flow grade ≥2 (44.4% and 23.7%, respectively; P=0.008).Conclusions:In patients with LMCA ACS, survival correlates with baseline hemodynamic and coronary flow status.
Despite its recommendation by the current guidelines, the role of long-term oral beta-blocker therapy has never been evaluated by randomized trials in uncomplicated ST-segment elevation myocardial ...infarction (STEMI) patients without heart failure, left ventricular dysfunction or ventricular arrhythmia who underwent primary percutaneous coronary intervention (PCI).
In a multi-center, open-label, randomized controlled trial, STEMI patients with successful primary PCI within 24 hours from the onset and with left ventricular ejection fraction (LVEF) ≥40% were randomly assigned in a 1-to-1 fashion either to the carvedilol group or to the no beta-blocker group within 7 days after primary PCI. The primary endpoint is a composite of all-cause death, myocardial infarction, hospitalization for heart failure, and hospitalization for acute coronary syndrome. Between August 2010 and May 2014, 801 patients were randomly assigned to the carvedilol group (N = 399) or the no beta-blocker group (N = 402) at 67 centers in Japan. The carvedilol dose was up-titrated from 3.4±2.1 mg at baseline to 6.3±4.3 mg at 1-year. During median follow-up of 3.9 years with 96.4% follow-up, the cumulative 3-year incidences of both the primary endpoint and any coronary revascularization were not significantly different between the carvedilol and no beta-blocker groups (6.8% and 7.9%, P = 0.20, and 20.3% and 17.7%, P = 0.65, respectively). There also was no significant difference in LVEF at 1-year between the 2 groups (60.9±8.4% and 59.6±8.8%, P = 0.06).
Long-term carvedilol therapy added on the contemporary evidence-based medications did not seem beneficial in selected STEMI patients treated with primary PCI.
CAPITAL-RCT (Carvedilol Post-Intervention Long-Term Administration in Large-scale Randomized Controlled Trial) ClinicalTrials.gov.number, NCT 01155635.
Although takotsubo syndrome (TTS) has been reported in patients with subarachnoid hemorrhage (SAH), its incidence and relation to the severity of SAH are unknown.Of 319 consecutive patients with ...aneurysmal SAH, 245 patients who underwent both the ECG and echocardiography were analyzed.The incidence of TTS was 6.9% (22 patients (21 women), median age 68 years (range, 60-83) ). Regional wall motion abnormalities were present as apical (64%), mid-ventricular (9%), basal (4%) and focal (23%) forms. Heart failure was found in 10 patients (45%) but there was no cardiac death. Regarding SAH severity, 10 patients (45%) with TTS were in World Federation of Neurosurgical Societies classification grade V, as compared to 40 patients (18%) without TTS (P = 0.005). Seven patients (32%) with TTS died during hospitalization, as compared to 26 patients (12%) without TTS (P = 0.018). Four patients (18%) with TTS were estimated as independent at discharge, as compared to 100 patients (45%) without TTS (P = 0.013).The incidence of TTS in patients with SAH was estimated as 6.9% with significant predominance of women. The severity of SAH was significantly greater in patients with TTS than in those without TTS.
Aims
The aim of this study was to elucidate the clinical characteristics, including frailty status, of patients with heart failure with preserved ejection fraction (HFpEF) in comparison with those in ...patients with heart failure with reduced ejection fraction (HFrEF) in a super‐aged region of Japan.
Methods and results
Of the 1061 Japanese patients enrolled in the Kochi YOSACOI study, a multicentre registry, we divided 645 patients (median age of 81 years interquartile range, 72–87 years; women, 49.1%) into two groups, HFpEF patients (61.2%) and HFrEF patients (38.8%). Physical frailty was diagnosed on the basis of the Japanese version of Cardiovascular Health (J‐CHS) Study criteria. Patients for whom left ventricular ejection fraction data were not available (n = 19), patients with heart failure with mildly reduced ejection fraction (n = 172), and patients who were not assessed by the J‐CHS criteria (n = 225) were excluded. The median ages of the HFpEF and HFrEF patients were 84 and 76 years, respectively. The proportion of patients with HFpEF gradually increased with advance of age. The proportion of patients with three or more comorbidities was larger in HFpEF patients than in HFrEF patients (77.9% vs. 65.6%, P = 0.003). Handgrip strength was significantly lower in HFpEF patients than in HFrEF patients for both men (P < 0.001) and women (P = 0.041). Comfortable 5 m walking speed was significantly slower in HFpEF patients than in HFrEF patients (P < 0.001). The proportions of patients with physical frailty were 55.2% in HFpEF patients and 46.8% in HFrEF patients, and the proportion was significantly higher in HFpEF patients (P = 0.043). In multivariate analysis, physical frailty was associated with advanced age odds ratio (OR), 1.030; 95% confidence interval (CI), 1.010–1.050; P = 0.023 and low albumin level (OR, 0.334; 95% CI, 0.192–0.582; P < 0.001) in HFpEF patients, and physical frailty was associated with women (OR, 2.150; 95% CI, 1.030–4.500; P = 0.042) and anaemia (OR, 2.840; 95% CI, 1.300–6.230; P = 0.003) in HFrEF patients.
Conclusions
In a super‐aged population of HF patients in Japan, HFpEF patients are more likely to be frail/have a high frailty status compared with HFrEF patients. The results suggested that physical frailty is associated with extracardiac factors in both HFpEF patients and HFrEF patients.
We assessed long-term outcomes after left main coronary artery (LMCA) stenting based on lesion types and stenting strategies. In the Assessing Optimal percutaneous coronary Intervention for Left Main ...Coronary Artery stenting registry, we evaluated 1,607 consecutive patients undergoing stent implantation for unprotected LMCA lesions (bifurcation lesions: n = 1318 and nonbifurcation lesions: n = 289). Among the bifurcation lesions, 1,281 lesions were treated with stenting across the bifurcation (bifurcation 1-stent strategy: n = 999 or bifurcation 2-stent strategy: n = 282). Among the nonbifurcation lesions, 219 lesions were treated with nonbifurcation stenting. The median follow-up duration was 4.6 (95% CI 4.5 to 4.8) years. The 5-year risk of bifurcation lesions relative to nonbifurcation lesions was neutral for target lesion revascularization (TLR) (adjusted hazard ratio HR 0.82, 95% CI 0.55 to 1.23, p = 0.34) and all-cause death (adjusted HR 1.22, 95% CI 0.87 to 1.71, p = 0.26). The risk of the bifurcation 1-stent strategy relative to nonbifurcation stenting in nonbifurcation lesions was also neutral for TLR (adjusted HR 1.19, 95% CI 0.74 to 1.90, p = 0.47) and all-cause death (adjusted HR 0.81, 95% CI 0.56 to 1.18, p = 0.27). However, the bifurcation 2-stent strategy was associated with worse clinical outcomes than the bifurcation 1-stent strategy in TLR (adjusted HR 1.76, 95% CI 1.23 to 2.52, p = 0.002) and definite or probable stent thrombosis (crude HR 3.50, 95% CI 1.32 to 9.33, p = 0.01), despite neutral risk for all-cause death (adjusted HR 1.00, 95% CI 0.74 to 1.36, p = 0.99). There was no definite or probable very late stent thrombosis up to 5 years. In conclusion, long-term outcomes after stent implantation for unprotected LMCA lesions were not dependent on the bifurcation lesion types but related to the bifurcation stenting strategies with worse outcomes for the bifurcation 2-stent strategy.
Background:The comparative efficacy of second-generation (G2) vs. first-generation (G1) drug-eluting stents (DES) for calcified coronary lesions is unknown.Methods and Results:We compared the 3-year ...clinical outcomes of patients with G1- or G2-DES according to the presence or absence of calcified coronary lesions as assessed in an angiographic core laboratory using data from 2 large-scale prospective multicenter randomized trials, RESET and NEXT. G1-DES and G2-DES were implanted in 299 and 1,033 patients, respectively, in the Calc stratum (≥1 lesion with moderate/severe calcification), and 1,208 and 3,550 patients, respectively, in the Non-calc stratum (no/mild calcification). The patients in the Calc stratum had a significantly higher adjusted risk for the primary outcome measure (any target-lesion revascularization (TLR)) than those in the Non-calc stratum (HR: 1.38, 95% CI: 1.11–1.71, P=0.004). The cumulative 3-year incidence of any TLR was not significantly different between the G1-DES and G2-DES groups in both the Calc and Non-calc strata (12.1% vs. 9.7%, P=0.22, and 6.8% vs. 6.1%, P=0.44, respectively). After adjusting for confounders, the effect of G2DES relative to G1-DES for any TLR remained insignificant in both the Calc and Non-calc strata (HR: 0.78, 95% CI: 0.48–1.25, P=0.3, and HR: 0.84, 95% CI: 0.61–1.17, P=0.31, respectively, P interaction=0.55).Conclusions:The effect of G2-DES relative to G1-DES for TLR was not significantly different regardless of the presence or absence of lesion calcification.
PDF
