Impact of periprocedural bleeding on mid-term outcome in nonagenarians who underwent transcatheter aortic valve implantation: insights from LAPLACE registry.

Data from several recent studies have demonstrated the safety and efficacy of transcatheter aortic valve implantation (TAVI) for severe aortic stenosis (AS) even in nonagenarians. However, the impact of periprocedural bleeding following TAVI on their outcome remains unclear. In the aLliAnce for exPloring cLinical prospects of AortiC valvE disease (LAPLACE) registry, we compared outcomes between the bleeding and no-bleeding groups among 1953 patients < 90 years old (mean age, 83.0 ± 4.6 years old) and 316 nonagenarians (mean age, 91.7 ± 1.9 years old) who underwent TAVI with a median follow-up period of 628 days. The group with any periprocedural bleeding showed a higher 30-day mortality than the no-bleeding group in patients < 90 years old (3.3% vs. 0.5%, p = 0.001) and nonagenarians (7.9% vs. 0.7%, p = 0.001). In patients < 90 years old, severe periprocedural bleeding (n = 85) was associated with a higher mid-term all-cause mortality rate than no severe bleeding (n = 1,868), even after adjusting for covariates (hazard ratio [HR], 1.994; 95% confidence interval [CI] 1.287-2.937; p = 0.002). On the other hand, in nonagenarians, any periprocedural bleeding (n = 38) was associated with a higher mid-term cardiovascular (CV) mortality rate (21.1% vs. 4.3%, log-rank p = 0.014) than no bleeding (n = 278), even after adjusting for covariates (HR, 3.104; 95% CI 1.140-8.449; p = 0.027). In conclusion, any periprocedural bleeding after TAVI was associated with mid-term CV mortality in nonagenarians, whereas severe bleeding was associated with mid-term all-cause mortality in patients < 90 years old.

A novel "proximal first" Inoue balloon catheter for retrograde aortic valvuloplasty: Initial case report.

The Inoue balloon, invented for percutaneous transseptal mitral commissurotomy for mitral stenosis, is initially dilated in the distal portion and then the proximal portion, forming an hourglass shape that stabilizes the balloon at the mitral valve orifice with a pulling action. The device has been successfully applied to antegrade aortic valvuloplasty; the hourglass shape stabilizes the balloon across the aortic valve without rapid ventricular pacing. Subsequently, an Inoue balloon was developed for retrograde aortic valvuloplasty using the same design as the antegrade balloon. The hourglass-shaped balloon, however, has difficulty maintaining stability across the aortic valve because the distal portion of the balloon, which inflates first, directly receives systolic pressure from the left ventricle. A novel Inoue balloon was invented to overcome this issue by altering the manner of inflation: the proximal portion inflates first, followed by the distal portion. Theoretically, the proximal portion, which initially inflates just above the aortic valve, remains secure across the valve by applying a pressing force that counteracts the systolic forward pressure. Furthermore, a radiopaque marker is placed at the center of the balloon to enable rapid and precise balloon adjustment. We present a case involving a 65-year-old female hemodialysis patient with severe symptomatic aortic stenosis who we successfully treated with balloon aortic valvuloplasty using the novel Inoue balloon followed by transcatheter aortic valve implantation. The present case demonstrates the feasibility and effectiveness of the novel "proximal first" Inoue balloon for retrograde balloon aortic valvuloplasty for severe aortic stenosis.

Impact of Chronic Kidney Disease on In-Hospital and 3-Year Clinical Outcomes in Patients With Acute Myocardial Infarction Treated by Contemporary Percutaneous Coronary Intervention and Optimal Medical Therapy　- Insights From the J-MINUET Study.

BACKGROUND: The impact of chronic kidney disease (CKD) on long-term outcomes following acute myocardial infarction (AMI) in the era of modern primary PCI with optimal medical therapy is still in debate.Methods and Results:A total of 3,281 patients with AMI were enrolled in the J-MINUET registry, with primary PCI of 93.1% in STEMI. CKD stage on admission was classified into: no CKD (eGFR ≥60 mL/min/1.73 m2); moderate CKD (60>eGFR≥30 mL/min/1.73 m2); and severe CKD (eGFR <30 mL/min/1.73 m2). While the primary endpoint was all-cause mortality, the secondary endpoint was major adverse cardiac events (MACE), defined as a composite of all-cause death, cardiac failure, myocardial infarction (MI) and stroke. Of the 3,281 patients, 1,878 had no CKD, 1,073 had moderate CKD and 330 had severe CKD. Pre-person-days age- and sex-adjusted in-hospital mortality significantly increased from 0.014% in no CKD through 0.042% in moderate CKD to 0.084% in severe CKD (P<0.0001). Three-year mortality and MACE significantly deteriorated from 5.09% and 15.8% in no CKD through 16.3% and 38.2% in moderate CKD to 36.7% and 57.9% in severe CKD, respectively (P<0.0001). C-index significantly increased from the basic model of 0.815 (0.788-0.841) to 0.831 (0.806-0.857), as well as 0.731 (0.708-0.755) to 0.740 (0.717-0.764) when adding CKD stage to the basic model in predicting 3-year mortality (P=0.013; net reclassification improvement [NRI] 0.486, P<0.0001) and MACE (P=0.046; NRI 0.331, P<0.0001) respectively. CONCLUSIONS: CKD remains a useful predictor of in-hospital and 3-year mortality as well as MACE after AMI in the modern PCI and optimal medical therapy era.

Validation of the atherothrombotic risk score for secondary prevention in patients with acute myocardial infarction: the J-MINUET study.

Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention (TRS2°P) is a contemporary risk scoring system for secondary prevention based on nine clinical factors. However, this scoring system has not been validated in other populations. The aim of this study was to validate the TRS2°P in patients with acute myocardial infarction (AMI) treated with primary percutaneous coronary intervention (PCI) in a nationwide registry cohort. Among 3283 consecutive patients with AMI enrolled in the Japanese registry of acute Myocardial INfarction diagnosed by Universal dEfiniTion (J-MINUET), a total of 2611 patients who underwent primary PCI were included in this study. The performance of the TRS2°P to predict major adverse cardiovascular events (MACE) composed of all-cause death, non-fatal MI, and non-fatal stroke up to 3 years in the present cohort was evaluated. The TRS2°P had modest discriminative performance in this J-MINUET cohort with a c-statistic of 0.63, similar to that in the derived cohort (TRA2°P-TIMI50, c-statistic 0.67). A strong graded relationship between the TRS2°P and 3-year cardiovascular event rates was also observed in the J-MINUET cohort. Age ≥ 75 years, Killip ≥ 2, prior stroke, peripheral artery disease, anemia, and non-ST-elevation myocardial infarction were identified as independent factors for the incidence of MACE. The TRS2°P modestly predicted secondary cardiovascular events among patients with AMI treated by primary PCI in a nationwide cohort of Japan. Further studies are needed to develop a novel risk score better predicting secondary cardiovascular events.

Long-Term Clinical Impact of Cardiogenic Shock and Heart Failure on Admission for Acute Myocardial Infarction.

Long-term clinical outcomes among patients with cardiogenic shock (CS) and heart failure (HF) who survive the early phase of acute myocardial infarction (AMI) remain uncertain. We investigated 3283 consecutive patients with AMI, selected from a prospective, nation-wide multicenter registry (J-MINUET) database comprising 28 institutions in Japan between July 2012 and March 2014. The 3263 eligible patients were divided into the following three groups: CS-/HF- group (n = 2467, 75.6%); CS-/HF+ group (n = 479, 14.7%); and CS+ group (n = 317, 9.7%). The thirty-day mortality rate in CS+ patients was 32.8%, significantly higher than in CS- patients. Among CS+ patients, multivariate logistic regression analysis identified statin use before admission (Odds ratio (OR) 0.32, 95% confidence interval (CI) 0.14-0.66, P = 0.002), renal deficiency (OR 8.72, 95%CI 2.81-38.67, P < 0.0001) and final thrombolysis in myocardial infarction flow grade (OR 0.42, 95%CI 0.18-0.99, P = 0.046) were associated with 30-day mortality. Landmark Kaplan-Meier analysis showed that mortality rates after 30 days were comparable between CS+ and CS-/HF+ groups but were lower in the CS-/HF- group. Multivariate Cox hazard analysis also showed that hazard risk of mortality after 30 days was comparable between the CS+ and CS-/HF+ groups (Hazard ratio (HR) 1.03, 95%CI 0.63-1.68, P = 0.90), and significantly lower in the CS-/HF- group (HR 0.44, 95%CI 0.32-059, P < 0.0001). In conclusion, AMI patients with CS who survived 30 days experienced worse long-term outcomes compared with those without CS up to 3 years. Attention is required for patients who show HF on admission without CS to improve long-term AMI outcomes.

Prolonged Intensive Care Unit Stay Following Transcatheter Aortic Valve Replacement.

PURPOSE: Postoperative intensive care unit (ICU) stay after cardiac surgeries has been extensively studied, but little attention has been given to ICU stay following transcatheter aortic valve replacement (TAVR). This study examined ICU stay after TAVR. METHODS: Two hundred and forty-five patients who underwent TAVR between April 2010 and October 2016 were studied retrospectively. We investigated the status of ICU stay, the predictors of prolonged ICU stay (PICUS), and its impact on short- and long-term outcomes. Prolonged ICU stay was defined as post-TAVR ICU stay longer than 2 days (day of TAVR + 1 day). RESULTS: Length of ICU stay was 2.6 ± 4.9 days, and PICUS was identified in 14.7% of the patients. The predominant reason for PICUS was congestive heart failure or circulatory failure (41.7%). Pulmonary dysfunction and nontransfemoral approach were independent predictors of PICUS (pulmonary dysfunction: odds ratio = 2.64, 95% confidence interval [CI]: 1.05-7.35; nontransfemoral approach: odds ratio = 2.81, 95% CI: 1.15-6.89). Prolonged ICU stay was associated with higher rate of 30-day combined end point (PICUS vs non-PICUS: 44.4% vs 3.3%, P < .0001), longer postoperative hospital stay (49.9 ± 141.9 days vs 12.0 ± 6.0 days, P < .0001), and lower rate of discharge home (77.8% vs 95.2%, P = .0002). Patients with PICUS had worse long-term survival (P < .0001), and PICUS was a predictor of mortality (hazard ratio: 4.21, 95% CI: 2.09-8.22). CONCLUSION: Prolonged ICU stay following TAVR was found in 14.7%, and pulmonary dysfunction and nontransfemoral approach were associated with PICUS. Short- and long-term prognoses were worse in patients with PICUS than those without.

Transcatheter aortic valve implantation-related futility: prevalence, predictors, and clinical risk model.

Futility denotes failure to achieve the projected outcome. We investigated the prevalence, predictors, and clinical risk model of transcatheter aortic valve implantation (TAVI)-related futility. We included 464 consecutive patients undergoing TAVI from 2010 to 2017. Futility was defined as death and/or hospitalization for heart failure (HFH) within 1 year after TAVI. Of 464 patients (mean age: 84.4 years), 69% were females (EuroSCOREII: 6.3%; Society of Thoracic Surgeons [STS] score: 6.9%). Forty-six patients (9.9%) experienced TAVI-related futility, and 36 of 46 patients (69.6%) died within 1 year due to cardiac (37.5%) and non-cardiac (62.5%) causes. Previous HFH (hazard ratio [HR], 2.20; 95% confidence interval [CI]: 1.13-4.35, p = 0.020), chronic obstructive pulmonary disease (COPD) (HR, 3.39; 95% CI: 1.12-8.42, p = 0.033), and moderate/severe mitral or tricuspid regurgitation (HR, 2.98; 95% CI: 1.32-6.27, p = 0.010) were independent predictors of futility. With 1 point assigned to each predictor (total 0 point, futility low-risk; total 1 point, futility intermediate-risk; total 2-3 points, futility high-risk), the futility risk model clearly stratified individual futility risk into three groups (the freedom from futility at 1 year: 96.2%, 82.1%, and 67.9% each). Our futility risk model presented better discrimination than EuroSCOREII, and STS score (c-statistic: 0.73 vs. 0.68 vs. 0.67). Medical futility was recognized in 9.9% of patients undergoing TAVI. Previous HFH, COPD, and concomitant atrioventricular regurgitation were associated with futility. The risk model derived from three predictors showed good performance in predicting futility risk.

Prognostic Impact of B-Type Natriuretic Peptide on Long-Term Clinical Outcomes in Patients with Non-ST-Segment Elevation Acute Myocardial Infarction Without Creatine Kinase Elevation.

Although B-type natriuretic peptide (BNP) has gradually gained recognition as an indicator in risk stratification for patients with acute myocardial infarction (AMI), the prognostic impact on long-term clinical outcomes in patients with non-ST-segment elevation acute myocardial infarction (NSTEMI) without creatine kinase (CK) elevation remains unclear.This prospective multicenter study assessed 3,283 consecutive patients with AMI admitted to 28 institutions in Japan between 2012 and 2014. We analyzed 218 patients with NSTEMI without CK elevation (NSTEMI-CK) for whom BNP was available. In the NSTEMI-CK group, patients were assigned to high- and low-BNP groups according to BNP values (cut-off BNP, 100 pg/mL). The primary endpoint was defined as a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, cardiac failure, and urgent revascularization for unstable angina up to 3 years. Primary endpoints were observed in 60 (33.3%) events among patients with NSTEMI-CK. Kaplan-Meier analysis revealed a significantly higher event rate for primary endpoints among patients with high BNP (log-rank P < 0.001). After adjusting for covariates, a higher BNP level was significantly associated with long-term clinical outcomes in NSTEMI-CK (adjusted hazard ratio, 4.86; 95% confidence interval, 2.18-12.44; P < 0.001).The BNP concentration is associated with adverse long-term clinical outcomes among patients with NSTEMI-CK who are considered low risk. Careful clinical management may be warranted for secondary prevention in patients with NSTEMI-CK with high BNP levels.

Usefulness of the Transcatheter Aortic Valve Replacement Risk Score to Determine Mid-Term Outcomes.

BACKGROUND: The purpose of this study was to investigate if the transcatheter aortic valve replacement (TAVR) risk score can independently predict outcomes following TAVR, and to evaluate its predictive performance.Methods and Results:This retrospective multicenter study comprised 682 patients with severe aortic stenosis who underwent TAVR. The primary endpoint was all-cause death following TAVR. The clinical model was established using variables identified as independent predictors in the multivariate analysis. Incremental values were assessed after adding atrial fibrillation, body mass index (BMI), and serum albumin to the TAVR risk score in receiver-operating characteristic analysis. The median TAVR risk score was 2.1% with a mean follow-up of 505 days. On Kaplan-Meier analysis, a TAVR risk score >4% had lowest survival rate, whereas TAVR risk score ≤2% had the highest survival rate at 3 years (log-rank P<0.001). The multivariate Cox regression analysis found the TAVR risk score was independently associated with all-cause death, and demonstrated moderate predictive performance for predicting all-cause death at 3 years. However, if each independent predictor is added to the model, it significantly increased discriminatory performance, particularly with BMI and serum albumin level. CONCLUSIONS: We demonstrated that the TAVR risk score could independently predict mid-term death following TAVR, and had greater predictive performance for predicting all-cause death at 3 years with BMI and serum albumin level.

Admission Heart Rate Is a Determinant of Effectiveness of Beta-Blockers in Acute Myocardial Infarction Patients.

BACKGROUND: Beta-blockers are standard therapy for acute myocardial infarction (AMI). However, despite current advances in the management of AMI, it remains unclear whether all AMI patients benefit from ß-blockers. We investigated whether admission heart rate (HR) is a determinant of the effectiveness of ß-blockers for AMI patients. Methods and Results: We enrolled 3,283 consecutive AMI patients who were admitted to 28 participating institutions in the Japanese Registry of Acute Myocardial Infarction Diagnosed by Universal Definition (J-MINUET) study. According to admission HR, we divided patients into 3 groups: bradycardia (HR <60 beats/min, n=444), normocardia (HR 60 to ≤100 beats/min, n=2,013), and tachycardia (HR >100 beats/min, n=342). The primary endpoint was major adverse cardiac events (MACE), including all-cause death, non-fatal MI, non-fatal stroke, heart failure (HF), and urgent revascularization for unstable angina, at 3-year follow-up. Beta-blocker at discharge was significantly associated with a lower risk of MACE in the tachycardia group (23.6% vs. 33.0%; P=0.033), but it did not affect rates of MACE in the normocardia group (17.8% vs. 18.4%; P=0.681). In the bradycardia group, ß-blocker use at discharge was significantly associated with a higher risk of MACE (21.6% vs. 12.7%; P=0.026). Results were consistent for multivariable regression and stepwise multivariable regression. CONCLUSIONS: Admission HR might determine the efficacy of ß-blockers for current AMI patients.

Clinical features of potential after-effects of percutaneous coronary intervention in the treatment of silent myocardial ischemia.

Clinical predictors for later adverse cardiovascular events in patients undergoing percutaneous coronary intervention (PCI) for silent myocardial ischemia remain undetermined. We investigated clinical features leading to later adverse cardiovascular events in patients who underwent PCI for silent myocardial ischemia. Of a total of 294 consecutive patients with a diagnosis of silent myocardial ischemia who successfully underwent contemporary PCI in our institute between January 2013 and December 2014, an initial event of any of all-cause death, hospitalized heart failure, acute coronary syndromes, and target vessel revascularization were identified as later adverse cardiovascular events and evaluated an association of them with baseline clinical characteristics. Silent myocardial ischemia was defined by an assessment of either electrocardiogram, myocardial perfusion imaging, coronary angiogram, or coronary fractional flow reserve. During a median follow-up of 565 days (interquartile range 361-816), later adverse cardiovascular events were identified in 38 patients (13%) consisting of 6 deaths, 5 hospitalized heart failures, 2 acute coronary syndromes, and 25 target vessel revascularizations. A presence of chronic kidney disease and/or insulin-treated diabetes mellitus, but not other clinical features, was strongly associated with later adverse cardiovascular events (hazard ratio 8.22; 95% confidential interval 2.95-29.25, P < 0.0001). Those events were increased in accordance with advanced stages of chronic kidney disease (P = 0.0003). A presence of chronic kidney disease and/or insulin-treated diabetes mellitus may lead the potential after-effects of PCI in the treatment of silent myocardial ischemia.

Is systolic blood pressure high in patients with acute aortic dissection on first medical contact before hospital transfer?

Acute aortic dissection (AAD) cases are thought to have high blood pressure (BP) on admission; however, little data are available on BP prior to admission. The purpose of this study was to investigate systolic blood pressure (SBP) very early after symptom onset and before hospital transfer in patients with AAD to determine whether SBPs were high, and also whether SBPs were higher or lower compared with SBPs at hospital admission. We obtained results using three-year data derived from the Tokyo Acute Aortic Super Network Database. First, we selected 830 patients with AAD for which the "duration from symptom onset to first medical contact by ambulance crews" (SO-FMC) was within 60 min. We examined the SBPs of such patients. Next, we selected 222 patients with AAD whose SBPs were measured both at FMC, within 15 min after symptom onset, and at hospital admission, and compared SBPs at FMC with those at hospital admission. Among types A (n = 190) and B (n = 117), in patients with an SO-FMC ≤ 15 min, the median SBP was 100 mmHg and 178 mmHg (p < 0.001), respectively; 9% and 50% (p < 0.001) of such patients, respectively, exhibited an SBP ≥ 180 mmHg; and 43% and 10% (p < 0.001) of such patients, respectively, had an SBP < 90 mmHg. Of patients with types A (n = 124) and B (n = 98) AAD whose SBPs were measured both at FMC, within 15 min after symptom onset, and at hospital admission, SBPs at FMC were higher than those at hospital admission for the SBP ≥ 180 mmHg subgroups of both type A (194 mmHg vs. 159 mmHg, p < 0.001) and type B (199 mmHg vs. 186 mmHg, p < 0.001). Approximately 10 min after symptom onset and before hospital transfer, the measured SBPs of many patients with type A AAD were not necessarily high. However, the SBPs of cases with type B AAD were high as previously reported for SBP on admission. In addition, for the subgroup of SBP ≥ 180 mmHg at FMC within 15 min after symptom onset, SBPs at FMC were significantly higher than those at hospital admission for both types A and B; the higher SBP at symptom onset may have been partially associated with being a trigger of AD.

Association of onset-season with characteristics and long-term outcomes in acute myocardial infarction patients: results from the Japanese registry of acute myocardial infarction diagnosed by universal definition (J-MINUET) substudy.

It is known that incidence and short-term mortality rate of acute myocardial infarction (AMI) tend to be higher in the cold season. The aim of our study was to investigate the association of onset-season with patient characteristics and long-term prognosis of AMI. This was a prospective, multicenter, Japanese investigation of 3,283 patients with AMI who were hospitalized within 48 h of symptom onset between July 2012 and March 2014. Patients were divided into 3 seasonal groups according to admission date: cold season group (December-March), hot season group (June-September), and moderate season group (April, May, October, and November). We identified 1356 patients (41.3%) admitted during the cold season, 901 (27.4%) during the hot season, and 1026 (31.3%) during the moderate season. We investigated the seasonal effect on patient characteristics and clinical outcomes. Baseline characteristics of each seasonal group were comparable, with the exception of age, Killip class, and conduction disturbances. The rates of higher Killip class and complete atrioventricular block were significantly higher in the cold season group. The 3-year cumulative survival free from major adverse cardiac events (MACE) rate was the lowest in the cold season (67.1%), showing a significant difference, followed by the moderate (70.0%) and hot seasons (72.9%) (p < 0.01). Initial severity and long-term prognoses were worse in patients admitted during the cold season. Our findings highlight the importance of optimal prevention and follow-up of AMI patients with cold season onset.

Outcomes of Transcatheter Aortic Valve Implantation in Patients with Cirrhosis.

Cirrhosis is a significant adverse factor of cardiac surgeries. Transcatheter aortic valve implantation (TAVI) has evolved as a less invasive therapy for aortic stenosis, whereas detailed case analysis of TAVI in cirrhotic patients is limited.Among 444 consecutive patients who underwent TAVI in the Sakakibara Heart Institute between October 2013 and January 2018, we retrospectively reviewed 11 patients (2.5%) with cirrhosis. All outcomes were defined according to the Valve Academic Research Consortium-2 criteria.The median age of the patients was 82 years, and eight (73%) were female. Seven patients (64%) were Child-Turcotte-Pugh class A, and four patients (36%) were class B. The Model for End-Stage Liver Disease score was 10 (7.0-13). TAVI was performed using Edwards SAPIEN XT/SAPIEN3 in nine patients (82%), and Medtronic CoreValve/Evolut R in two patients (18%), via transfemoral (n = 8, 73%) or transapical (n = 3, 27%) approach. The device success rate was 100% and no extracorporeal circulation had been inducted. No death, stroke, life-threatening bleeding, and acute kidney injury stage 2 or 3 occurred within 30 days, but three major bleeding events (27%) were documented (two access-site bleeding in transapical approach, and one pulmonary hemorrhage caused by transient mitral regurgitation). During a median follow-up of 493 days, four deaths had occurred, and the mid-term survival rate was 81% and 65% at one and two years each.TAVI is a promising therapeutic option for patients with cirrhosis. Further study should be needed regarding optimal patient selection and procedures in patients with cirrhosis.

Impact of Frailty Markers for Unplanned Hospital Readmission Following Transcatheter Aortic Valve Implantation.

BACKGROUND: Various frailty markers have been developed to guide better patient selection for transcatheter aortic valve implantation (TAVI). This study aimed to investigate the frequency and specific causes of unplanned hospital readmission after TAVI, and to investigate which frailty markers better predicted outcomes.Methods and Results:We retrospectively reviewed 155 patients for whom we calculated their Short Physical-Performance Battery (SPPB), Placement of AoRTic TraNscathetER Valve (PARTNER) frailty scale, frailty index, clinical frailty scale, modified Fried scale, and gait speed. The primary endpoint was unplanned readmission following TAVI. The clinical model was established using variables that were identified as independent predictors in multivariate analysis. Incremental values were assessed after adding each frailty marker to the clinical model, and were compared between frailty markers. Although unplanned readmission <30 days was 1.9%, 23% of patients had an unplanned readmission following TAVI mainly because of heart failure and pneumonia within 1 year. Frailty markers other than the modified Fried scale were independently associated with unplanned readmission. The SPPB and the PARTNER frailty scale significantly increased discriminatory performance for predicting unplanned readmission. CONCLUSIONS: Unplanned readmissions following TAVI in the present study were fewer than previously reported. There seems to be a difference between frailty markers in their predictive performance. Precise frailty assessment may result in reducing unplanned admissions after TAVI and therefore better quality of life.

Outcomes of patients requiring extracorporeal membrane oxygenation in transcatheter aortic valve implantation: a clinical case series.

Transcatheter aortic valve implantation (TAVI) has been established as a low-invasive therapy for aortic stenosis, but circulatory collapse necessitating mechanical circulatory support could occur during TAVI due to procedure itself or procedural complications. The purpose of this study is to describe the outcomes of patients requiring extracorporeal membrane oxygenation (ECMO) in TAVI. Among 384 consecutive patients undergoing TAVI from April 2010 to July 2017 in Sakakibara Heart Institute, we evaluated seven patients (1.8%) who required ECMO during procedure. The definitions of outcome were derived from Valve Academic Research Consortium-2 criteria. The indication of ECMO included bridge to emergent surgery due to mechanical complication (n = 3) [aortic root rupture (n = 2), and left-ventricle rupture (n = 1); emergent use], bridge to recovery from cardiac stunning (n = 3; emergent use), and circulatory support for cardiogenic shock (n = 1; prophylactic use). All patients were cannulated from femoral artery and vein, and there was no ECMO-related complication. Six out of seven patients were weaned from ECMO during the TAVI procedure, whereas the other patient with annulus rupture died the following day after TAVI. Five patients survived to discharge [postoperative hospital stay: 27.6 ± 24.3 (23) days]. During mean follow-up of 253 days, a total of three patients died due to annulus rupture, refractory heart failure, and pneumonia, respectively. ECMO is effective and a safe mechanical support device during TAVI. The mid-term outcomes of patients who needed ECMO were unfavorable. Further evolution of transcatheter heart valve is essential, and prophylactic ECMO may contribute to better prognosis in selected patients.

Low-density lipoprotein cholesterol targeting with pitavastatin + ezetimibe for patients with acute coronary syndrome and dyslipidaemia: the HIJ-PROPER study, a prospective, open-label, randomized trial.

AIMS: To elucidate the effects of intensive LDL-C lowering treatment with a standard dose of statin and ezetimibe in patients with dyslipidaemia and high risk of coronary events, targeting LDL-C less than 70 mg/dL (1.8 mmol/L), compared with standard LDL-C lowering lipid monotherapy targeting less than 100 mg/dL (2.6 mmol/L). METHODS AND RESULTS: The HIJ-PROPER study is a prospective, randomized, open-label trial to assess whether intensive LDL-C lowering with standard-dose pitavastatin plus ezetimibe reduces cardiovascular events more than standard LDL-C lowering with pitavastatin monotherapy in patients with acute coronary syndrome (ACS) and dyslipidaemia. Patients were randomized to intensive lowering (target LDL-C < 70 mg/dL [1.8 mmol/L]; pitavastatin plus ezetimibe) or standard lowering (target LDL-C 90 mg/dL to 100 mg/dL [2.3-2.6 mmol/L]; pitavastatin monotherapy). The primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, unstable angina, and ischaemia-driven revascularization. Between January 2010 and April 2013, 1734 patients were enroled at 19 hospitals in Japan. Patients were followed for at least 36 months. Median follow-up was 3.86 years. Mean follow-up LDL-C was 65.1 mg/dL (1.68 mmol/L) for pitavastatin plus ezetimibe and 84.6 mg/dL (2.19 mmol/L) for pitavastatin monotherapy. LDL-C lowering with statin plus ezetimibe did not reduce primary endpoint occurrence in comparison with standard statin monotherapy (283/864, 32.8% vs. 316/857, 36.9%; HR 0.89, 95% CI 0.76-1.04, P = 0.152). In, ACS patients with higher cholesterol absorption, represented by elevated pre-treatment sitosterol, was associated with significantly lower incidence of the primary endpoint in the statin plus ezetimibe group (HR 0.71, 95% CI 0.56-0.91). CONCLUSION: Although intensive lowering with standard pitavastatin plus ezetimibe showed no more cardiovascular benefit than standard pitavastatin monotherapy in ACS patients with dyslipidaemia, statin plus ezetimibe may be more effective than statin monotherapy in patients with higher cholesterol absorption; further confirmation is needed. TRIAL NO: UMIN000002742, registered as an International Standard Randomized Controlled Trial.

Renoprotective Transcatheter Aortic Valve Implantation Without Contrast Media.

The therapeutic role of transcatheter aortic valve implantation (TAVI) in high surgical risk or inoperable cases has been established. Most of the candidates for TAVI are elderly and have multiple comorbidities including chronic kidney disease. However, contrast-enhanced computed tomography and coronary angiography, both of which require iodine contrast media, are essential for pre-procedural planning. In addition, TAVI could have adverse effects on kidney function including contrast media-induced nephrotoxicity. Acute kidney injury following TAVI has been reported to be related to poor prognosis. In a case with advanced renal dysfunction, we successfully avoided post-procedural acute kidney injury by performing pre-procedural evaluation using minimal contrast and TAVI without contrast media. If anatomical conditions and experiences of the heart team are adequate, renoprotective TAVI should be a favorable therapy for patients with aortic stenosis complicated by renal dysfunction.

Five-Year Outcomes of the First Pivotal Clinical Trial of Balloon-Expandable Transcatheter Aortic Valve Replacement in Japan (PREVAIL JAPAN).

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has been an alternative less invasive therapy for high-surgical risk/inoperable patients with aortic valve stenosis (AS) in Japan. We report 5-year outcomes of the first pivotal clinical trial of TAVR in Japan (PREVAIL JAPAN).Methods and Results:A total of 64 patients with AS who were considered unsuitable candidates for surgery were enrolled at 3 centers in Japan (mean age: 84.3±6.1 years, female: 65.6%, STS score: 9.0±4.5%). Transfemoral approach (TF) and transapical approach (TA) was performed in 37 patients and 27 patients, respectively. At 5 years, freedom from all-cause death was 52.7% (TF: 51.3%, TA: 56.3%). Risk of all stroke at 5-year was 15.8% (TF: 8.9%, TA: 25.5%) and risk of major adverse cardiac and cerebrovascular events at 5 years was 58.0% (TF: 51.3%, TA: 69.2%). Mild or greater aortic regurgitation (AR) at 1 week was not associated with increased all-cause death at 5 years (69.1%) compared with none or trace AR (48.3%) (P=0.184). Patients with high STS score (>8) had higher mortality rate than those with low STS scores (≤8). CONCLUSIONS: The 5-year data from PREVAIL JAPAN show the clinical benefit of TAVR and suggest that balloon-expandable TAVR is an effective treatment option for Japanese patients with severe AS who are not suitable for surgery. (Funded by Edwards Lifesciences Limited; ClinicalTrials.gov number, NCT01113983.).

AVJ-514 Trial　- Baseline Characteristics and 30-Day Outcomes Following MitraClip® Treatment in a Japanese Cohort.

BACKGROUND: The MitraClip®system is a transcatheter-based therapeutic option for patients with chronic mitral regurgitation (MR) who are at high risk for surgery. A prospective, multicenter, single-arm study was initiated to confirm the transferability of this system to Japan.Methods and Results:Patients with symptomatic chronic moderate-to-severe (3+) or severe (4+) functional or degenerative MR with a Society of Thoracic Surgery (STS) score ≥8%, or the presence of 1 predefined risk factor were enrolled. Patients with left ventricular (LV) ejection fraction (EF) <30% were excluded. MR severity and LV function were assessed by an independent echocardiography core lab. Primary outcome included major adverse events (MAE) at 30 days and acute procedural success (APS). A total of 30 patients (age: 80±7 years; STS score: 10.3%±6.6%) were treated with the MitraClip®. At baseline, all patients had MR 3+/4+ with 53%/47% patients with degenerative/functional etiology with mean LVEF of 50.2±12.8%, and 37% of patients were NYHA class III/IV. APS was achieved in 86.7% with no occurrence of MAE. At 30 days, 86.7% of patients had MR ≤2+ and 96.7% were NYHA class I/II. CONCLUSIONS: The MitraClip®procedure resulted in clinically meaningful improvements in MR severity, function and quality of life measures, and low MAE rates. These early results suggest the transferability of this therapy to appropriately selected Japanese patients. (Trial Registration: clinicaltrials.gov Identifier NCT02520310.).