Polypharmacy and Bleeding Outcomes After Percutaneous Coronary Intervention.

BACKGROUND: Polypharmacy was reported to be associated with major bleeding in various populations. However, there are no data on polypharmacy and its association with bleeding in patients undergoing percutaneous coronary intervention (PCI).Methods and Results: Among 12,291 patients in the CREDO-Kyoto PCI Registry Cohort-3, we evaluated the number of medications at discharge and compared major bleeding, defined as Bleeding Academic Research Consortium Type 3 or 5 bleeding, across tertiles (T1-3) of the number of medications. The median number of medications was 6, and 88.0% of patients were on ≥5 medications. The cumulative 5-year incidence of major bleeding increased incrementally with increasing number of medications (T1 [≤5 medications] 12.5%, T2 [6-7] 16.5%, and T3 [≥8] 20.4%; log-rank P<0.001). After adjusting for confounders, the risks for major bleeding of T2 (hazard ratio [HR] 1.21; 95% confidence interval [CI] 1.08-1.36; P=0.001) and T3 (HR 1.27; 95% CI 1.12-1.45; P<0.001) relative to T1 remained significant. The adjusted risks of T2 and T3 relative to T1 were not significant for a composite of myocardial infarction or ischemic stroke (HR 0.95 [95% CI 0.83-1.09; P=0.47] and HR 1.06 [95% CI 0.91-1.23; P=0.48], respectively). CONCLUSIONS: In a real-world population of patients undergoing PCI, approximately 90% were on ≥5 medications. Increasing number of medications was associated with a higher adjusted risk for major bleeding, but not ischemic events.

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.

Percutaneous coronary intervention using new-generation drug-eluting stents versus coronary arterial bypass grafting in stable patients with multi-vessel coronary artery disease: From the CREDO-Kyoto PCI/CABG registry Cohort-3.

AIMS: There is a scarcity of studies comparing percutaneous coronary intervention (PCI) using new-generation drug-eluting stents (DES) with coronary artery bypass grafting (CABG) in patients with multi-vessel coronary artery disease. METHODS AND RESULTS: The CREDO-Kyoto PCI/CABG registry Cohort-3 enrolled 14927 consecutive patients who underwent first coronary revascularization with PCI or isolated CABG between January 2011 and December 2013. The current study population consisted of 2464 patients who underwent multi-vessel coronary revascularization including revascularization of left anterior descending coronary artery (LAD) either with PCI using new-generation DES (N = 1565), or with CABG (N = 899). Patients in the PCI group were older and more often had severe frailty, but had less complex coronary anatomy, and less complete revascularization than those in the CABG group. Cumulative 5-year incidence of a composite of all-cause death, myocardial infarction or stroke was not significantly different between the 2 groups (25.0% versus 21.5%, P = 0.15). However, after adjusting confounders, the excess risk of PCI relative to CABG turned to be significant for the composite endpoint (HR 1.27, 95%CI 1.04-1.55, P = 0.02). PCI as compared with CABG was associated with comparable adjusted risk for all-cause death (HR 1.22, 95%CI 0.96-1.55, P = 0.11), and stroke (HR 1.17, 95%CI 0.79-1.73, P = 0.44), but with excess adjusted risk for myocardial infarction (HR 1.58, 95%CI 1.05-2.39, P = 0.03), and any coronary revascularization (HR 2.66, 95%CI 2.06-3.43, P<0.0001). CONCLUSIONS: In this observational study, PCI with new-generation DES as compared with CABG was associated with excess long-term risk for major cardiovascular events in patients who underwent multi-vessel coronary revascularization including LAD.

Coronary Artery Disease Without Standard Cardiovascular Risk Factors.

Recently, one observational study showed that patients with ST-segment elevation myocardial infarction (STEMI) without standard cardiovascular risk factors were associated with increased mortality compared with patients with risk factors. This unexpected result should be evaluated in other populations including those with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and chronic coronary syndrome (CCS). Among 30,098 consecutive patients undergoing first coronary revascularization in the CREDO-Kyoto PCI/CABG (Coronary Revascularization Demonstrating Outcome Study in Kyoto Percutaneous Coronary Intervention/Coronary Artery Bypass Grafting) registry cohort-2 and 3, we compared clinical characteristics and outcomes between patients with and without risk factors stratified by their presentation (STEMI n = 8,312, NSTE-ACS n = 3,386, and CCS n = 18,400). Patients with risk factors were defined as having at least one of the following risk factors: hypertension, dyslipidemia, diabetes, and current smoking. The proportion of patients without risk factors was low (STEMI: 369 patients [4.4%], NSTE-ACS: 110 patients [3.2%], and CCS: 462 patients [2.5%]). Patients without risk factors compared with those with risk factors more often had advanced age, low body weight, and malignancy and less often had history of atherosclerotic disease and prescription of optimal medical therapy. In patients with STEMI, patients without risk factors compared with those with risk factors were more often women and more often had atrial fibrillation, long door-to-balloon time, and severe hemodynamic compromise. During a median of 5.6 years follow-up, patients without risk factors compared with those with risk factors had higher crude incidence of all-cause death. After adjusting confounders, the mortality risk was significant in patients with CCS (hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.01 to 1.49, p = 0.04) but not in patients with STEMI (HR 1.06, 95% CI 0.89 to 1.27, p = 0.52) and NSTE-ACS (HR 1.07, 95% CI, 0.74 to 1.54, p = 0.73). In conclusion, among patients undergoing coronary revascularization, patients without standard cardiovascular risk factors had higher crude incidence of all-cause death compared with those with at least one risk factor. After adjusting confounders, the mortality risk was significant in patients with CCS but not in patients with STEMI and NSTE-ACS.

Effect of Polypharmacy on Long-Term Mortality After Percutaneous Coronary Intervention.

Polypharmacy was reported to be associated with increased mortality in various populations. However, there is a scarcity of data on status of polypharmacy and association with long-term mortality in patients who underwent percutaneous coronary intervention (PCI). Among 12,291 patients who underwent first PCI in the CREDO-Kyoto PCI/CABG registry Cohort-3, we evaluated the number of medications at discharge from index PCI hospitalization, and compared long-term mortality across the 3 groups divided by the tertiles of the number of medications. The median number of medications was 6 (interquartile range: 5 to 8), and 88.0% of the patients were on >=5 medications. Most of medications were those related to cardiovascular disease. Patients taking more medications were older and more often had co-morbidities and guideline-indicated medications. The cumulative 5-year incidence of all-cause death increased incrementally with increasing number of medications (Tertile 1 [<=5]: 13.1%, Tertile 2 [6 to 7]: 13.9%, and Tertile 3 [>=8]: 18.0%, log-rank p <0.001). After adjusting confounders, the mortality risks of Tertile 2 and Tertile 3 relative to Tertile 1 were no longer significant (Tertile 2: hazard ratio 0.93; 95% confidence interval 0.84 to 1.04; p = 0.23, and Tertile 3: hazard ratio 0.91; 95% confidence interval 0.81 to 1.03; p = 0.14, respectively). In conclusion, in a real-world population of patients who underwent PCI, approximately 90% of patients were on >=5 medications. Increasing medications was associated with higher crude incidence of all-cause death, whereas adjusted mortality risks were similar regardless of the number of medications. These data might suggest that achievement of optimal medical therapy would be preferred, even if it might increase the number of medications used.

Coronary Revascularization in the Past Two Decades in Japan (From the CREDO-Kyoto PCI/CABG Registries Cohort-1, -2, and -3).

The treatment of coronary artery disease has substantially changed over the past two decades. However, it is unknown whether and how much these changes have contributed to the improvement of long-term outcomes after coronary revascularization. We assessed trends in the demographics, practice patterns and long-term outcomes in 24,951 patients who underwent their first percutaneous coronary intervention (PCI) (n = 20,106), or isolated coronary artery bypass grafting (CABG) (n = 4,845) using the data in a series of the CREDO-Kyoto PCI/CABG Registries (Cohort-1 [2000 to 2002]: n = 7,435, Cohort-2 [2005 to 2007]: n = 8,435, and Cohort-3 [2011 to 2013]: n = 9,081). From Cohort-1 to Cohort-3, the patients got progressively older across subsequent cohorts (67.0 ± 10.0, 68.4 ± 9.9, and 69.8 ± 10.2 years, ptrend < 0.001). There was increased use of PCI over CABG (73.5%, 81.9%, and 85.2%, ptrend < 0.001) and increased prevalence of evidence-based medications use over time. The cumulative 3-year incidence of all-cause death was similar across the 3 cohorts (9.0%, 9.0%, and 9.3%, p = 0.74), while cardiovascular death decreased over time (5.7%, 5.1%, and 4.8%, p = 0.03). The adjusted risk for all-cause death and for cardiovascular death progressively decreased from Cohort-1 to Cohort-2 (HR:0.89, 95%CI:0.80 to 0.99, p = 0.03, and HR:0.80, 95%CI:0.70 to 0.92, p = 0.002, respectively), and from Cohort-2 to Cohort-3 (HR:0.86, 95%CI:0.78 to 0.95, p = 0.004, and HR:0.77, 95%CI:0.67-0.89, p < 0.001, respectively). The risks for stroke and repeated coronary revascularization also improved over time. In conclusions, we found a progressive and substantial reduction of adjusted risk for all-cause death, cardiovascular death, stroke, and repeated coronary revascularization over the past two decades in Japan.

Comparison of Outcomes of Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting Among Patients With Three-Vessel Coronary Artery Disease in the New-Generation Drug-Eluting Stents Era (From CREDO-Kyoto PCI/CABG Registry Cohort-3).

There is a scarcity of data comparing long-term clinical outcomes between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in patients with three-vessel coronary artery disease (3VD) in the new-generation drug-eluting stents era. CREDO-Kyoto PCI/CABG registry Cohort-3 enrolled 14927 consecutive patients who had undergone first coronary revascularization with PCI or isolated CABG between January 2011 and December 2013. We identified 2525 patients with 3VD (PCI: n = 1747 [69%], and CABG: n = 778 [31%]). The primary outcome measure was all-cause death. Median follow-up duration was 5.7 (interquartile range: 4.4 to 6.6) years. The cumulative 5-year incidence of all-cause death was significantly higher in the PCI group than in the CABG group (19.8% vs 13.2%, log-rank p = 0.001). After adjusting confounders, the excess risk of PCI relative to CABG for all-cause death remained significant (HR, 1.45; 95% CI, 1.14 to 1.86; p = 0.003), which was mainly driven by the excess risk for non-cardiovascular death (HR, 1.88; 95% CI, 1.30 to 2.79; p = 0.001), while there was no excess risk for cardiovascular death between PCI and CABG (HR, 1.19; 95% CI, 0.87 to 1.64; p = 0.29). There was significant excess risk of PCI relative to CABG for myocardial infarction (HR, 1.77; 95% CI, 1.19 to 2.69; p = 0.006), whereas there was no excess risk of PCI relative to CABG for stroke (HR, 1.24; 95% CI, 0.83 to 1.88; p = 0.30). In conclusion, in the present study population reflecting real-world clinical practice in Japan, PCI compared with CABG was associated with significantly higher risk for all-cause death, while there was no excess risk for cardiovascular death between PCI and CABG.

Mortality and predictors of survival in patients with recent ventricular septal rupture.

Ventricular septal rupture (VSR) is a rare but fatal complication after acute myocardial infarction (AMI). However, the mortality in patients with recent VSR and appropriate timing of surgical repair have not been clarified. To examine the background characteristics and mortality of VSR patients as well as the usefulness and appropriate timing of surgery in this patient cohort. Among 3,947 consecutive patients with AMI at our hospital, 39 patients diagnosed with VSR from 2002 to 2020 were included in the analysis. All patients underwent transthoracic echocardiography to confirm VSR on admission. Coronary angiography (CAG) and measurement of pulmonary-systemic flow ratio were performed before emergent surgery. The use of mechanical support devices before or after procedures was considered for all patients who underwent CAG. Basically, we performed emergent or urgent operations to patients who were in a shock state or who needed mechanical support. The final decision of the timing of the operation was made by the cardiac team. Patients' mean age was 76.3 years, and 33.3% of them were males. Most culprit lesions were located in the left anterior ascending artery (81.3%). The mean pulmonary-systemic flow ratio after VSR onset was 3.07 ± 1.98. On admission, 48.7% of patients were in a shock state. Surgical repair was possible in 28 patients at a median of 1 day after admission, with a mortality rate of 25%. Among all patients, the mortality rate was 43.6%. Survivors were significantly younger (71.3 ± 11.3 vs. 82.7 ± 6.2 years, p < 0.01), had higher mean arterial blood pressure (75.6 ± 14.4 vs. 62.8 ± 16.2 mmHg, p = 0.0496) and lower ejection fraction (44.3 ± 11.7% vs. 54.8 ± 7.9%, p = 0.04), and underwent surgical repair more frequently (95.5% vs. 41.2%, p < 0.01) than the non-survivors. In multivariate analysis, younger age (odds ratio [OR] 1.18 95% confidence interval [CI] 1.01-1.38, p = 0.04) and surgical repair (OR 0.04, 95% CI 0.00-0.73, p = 0.03) were significant predictors of survival. In surgical repair cases, time from admission to operation did not differ significantly between survivors and non-survivors. Surgical repair and younger age are predictors of survival in patients with recent VSR, but the timing of surgery was not.

Quadricuspid aortic valve repair by neo-cuspidization of an accessory cusp using autologous pericardium.

We present a successful case of the management of a 46-year-old woman with an abnormal aortic valve formed by four cusps (three equal large cusps and one smaller cusp; type B according to the Hurwitz and Roberts classification) with a marked loss of coaptation that caused a severe aortic insufficiency (AI). The patient underwent an aortic valvuloplasty of the defect using the glutaraldehyde (GA)-pretreated autologous pericardium, restoring the subnormal function and competency of the aortic valve. The postoperative course was unremarkable. The early follow-up showed a trivial AI and a significant reduction of regurgitant volume was identified in a cardiac magnetic resonance imaging (MRI) when compared to the preoperative state (27.2 vs. 2.1 ml). The follow-up transthoracic echocardiography 1 year after the surgery showed mild AI.

A novel risk score on admission for predicting death or need for surgery in patients with acute type A intramural hematoma receiving medical therapy.

There has been continuing discussion regarding the treatment strategy for acute type A intramural hematoma (IMH). Most patients are treated conservatively in Japan; hence, predicting fatal events and stratifying risks based on results normally obtained on hospital arrival are important. We aimed to examine the incidences and risk factors of death or need for surgery for acute type A IMH in patients receiving medical treatment and to identify high-risk patients using clinical findings on hospital arrival. From 2011 to 2016, 57 consecutive patients (mean age 72.5 years; male 36.8%) diagnosed with acute type A IMH who were receiving treatment at Shizuoka City Shizuoka Hospital were retrospectively included. Primary endpoint was a composite of cardiovascular death and operation within 1 year after onset. To evaluate sensitivity and specificity of the risk factors and risk score, we estimated the area under the receiver operating characteristic (ROC) curve. Mean follow-up duration was 621 days. Mean systolic blood pressure (SBP) was 129 mmHg. Computed tomography (CT) on arrival showed a mean ascending aorta diameter of 46 mm. Ulcer-like projection (ULP) in the ascending aorta and pericardial effusion (PE) were seen in 33% and 42% of cases, respectively. Twenty-eight patients (49.1%) reached the primary endpoint (cardiovascular death, 7 cases [12.3%]; operation, 21 cases [36.8%]). In univariate analysis of admission values, the primary endpoint group had significantly lower SBP (113.0 ± 28.5 vs 144.3 ± 33.5 mmHg), higher ascending aorta diameter (49.5 ± 8.1 vs 43.6 ± 5.9 mm), and higher frequency of ULP (53.8% vs 13.8%) and PE (58.6% vs 25.0%) than the event-free group. Multivariate analysis showed that ULP on admission CT was a significant predictor of the primary endpoint. The risk score was considered using these risk factors. On admission, the primary endpoint could be predicted with 89.7% sensitivity and 75% specificity (area under the ROC curve 0.823) if the patient had ULP and/or > 2 of the following factors: SBP < 120 mmHg, ascending aorta diameter > 45 mm, and PE. SBP and CT findings on arrival were significantly associated with cardiovascular death and the need for surgery in patients with acute type A IMH receiving initial medical therapy. The novel risk score was useful for predicting cardiovascular death and surgery.

Clinical outcomes of patients with pulmonary embolism versus deep vein thrombosis: From the COMMAND VTE Registry.

INTRODUCTION: Pulmonary embolism (PE) and deep vein thrombosis (DVT) can be considered as one clinical entity, venous thromboembolism (VTE). However, the potential differences between PE and DVT might have to be taken into consideration for the decision-making of the optimal treatment strategies. MATERIALS AND METHODS: The COMMAND VTE Registry is a multicenter registry enrolling 3027 consecutive patients with acute symptomatic VTE. The current study population consisted of 1715 PE patients with or without DVT and 1312 DVT only patients. RESULTS: The adjusted risk for recurrent VTE was not significantly different between the PE and DVT only groups (HR 1.22, 95%CI 0.93-1.60, P = 0.15). PE patients developed recurrent VTE events more often as PE than as DVT only (62% and 38%). The adjusted excess mortality risk of PE patients relative to DVT only patients was significant (HR 1.29, 95%CI 1.11-1.50, P < 0.001), with markedly higher cumulative 30-day incidence of all-cause death in PE patients (6.4% and 1.4%, P < 0.001). The most frequent cause of deaths was cancer death in both groups, and second most frequent cause of deaths in PE patients was fatal PE, most of which developed within 30 days. CONCLUSIONS: The risk for recurrent VTE was not significantly different between PE and DVT, although PE was more likely to develop recurrent VTE as PE. The mortality risk of PE seemed to be higher than that of DVT, which was more remarkable in the short term due to PE death, and less remarkable in the long term due to cancer death.

Right ventricular infarction caused by tricuspid ring annuloplasty.

Injury to the right coronary artery (RCA) is a rare complication of tricuspid annuloplasty. We report a patient who developed right ventricular (RV) infarction, because of tricuspid annuloplasty, and review management options.

Effects of Age and Sex on Clinical Outcomes After Percutaneous Coronary Intervention Relative to Coronary Artery Bypass Grafting in Patients With Triple-Vessel Coronary Artery Disease.

BACKGROUND: Age and sex are important considerations in the choice between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in daily clinical practice. METHODS AND RESULTS: Of 25 816 patients enrolled in the multicenter Coronary Revascularization Demonstrating Outcome Study in Kyoto (CREDO-Kyoto; Cohort-1, n=9877; Cohort-2, n=15 939), the present study population consisted of 5651 patients (men, n=3998; women, n=1653) with triple-vessel coronary artery disease who were considered to be pertinent in comparisons of PCI with CABG (PCI, n=3165; CABG, n=2486). Patients were divided into 3 groups according to the tertiles of age: ≤65 years (n=1972), 66 to 73 years (n=1820), and ≥74 years (n=1859). The excess adjusted mortality risk of PCI relative to CABG was significant in patients ≥74 years of age (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.10-1.79; P=0.006), whereas the risks were neutral in patients ≤65 years of age (HR, 1.05; 95% CI, 0.73-1.53; P=0.78) and in patients 66 to 73 years of age (HR, 1.03; 95% CI, 0.78-1.36; P=0.85; interaction P=0.003). The excess mortality risk of PCI relative to CABG was significant in men (HR, 1.24; 95% CI, 1.03-1.50; P=0.02) and trended to be significant in women (HR, 1.34; 95% CI, 0.98-1.84; P=0.07) without significant interaction between sex and the mortality risk of PCI relative to CABG (interaction P=0.40). CONCLUSIONS: There was a significant association between age and the mortality risk of PCI relative to CABG with excess risk in patients ≥74 years of age and neutral risk in younger patients. There was no significant sex-related difference in the mortality risk of PCI relative to CABG.

Clinical and angiographic outcomes with sirolimus-eluting stent for coronary bifurcation lesions. The J-PMS study.

BACKGROUND: Long-term outcomes of patients with bifurcated lesions and the restenotic response of the side branches after sirolimus-eluting stent (SES) implantation, comparing 1-stent with 2-stent treatment, are still under discussion. METHODS AND RESULTS: Japan Post-Marketing Surveillance Registry (J-PMS) is a prospective registry designed to evaluate the safety and efficacy of the SES in routine clinical practice. Angiograms of 1,063 patients with 1,250 lesions were analyzed at the independent core lab. Of these, 324 patients with bifurcation lesions were enrolled. Clinical endpoints were assessed at 3 years. Both main and side branches were evaluated by quantitative coronary angiography at post-procedure (n=349) and 8-month follow up (n=293). Two-stent treatment was performed in 12% of the cases. In-segment restenosis rates at 8 months were 25.6% in the side branch, but newly developed restenosis was seen in only 6.8%. Late loss at the carina of the side branch was -0.11mm in the 1-stent group. Major adverse cardiovascular events rate was 18.3% at 3 years. Target-lesion revascularization rate up to 3 years was 21.6% in the 2-stent group and 8.7% in the 1-stent group (P=0.037). Stent thrombosis occurred in 6 cases (2.0%) until 3 years. Of these, 4 cases were treated with 2-stent (10.81% vs. 0.76% in 1-stent, P=0.003, respectively). CONCLUSIONS: In a real-world setting, treatment of coronary bifurcation lesions using SES demonstrated favorable long-term outcomes as long as the side branch was not stented.