Coagulation, fibrinolysis and platelet drop in patients undergoing transfemoral transcatheter aortic valve implantation.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) leads to transient platelet activation and hypercoagulation status, resulting in thrombocytopenia. AIMS: This study investigated the associations of coagulation/fibrinolysis status after transfemoral TAVI with valve type, post-TAVI thrombocytopenia, and complication of TAVI. METHODS: Thrombin-antithrombin complex (TAT) and fibrin/fibrinogen degradation product (FDP) levels were measured before and 1 h, 1 day, and 2 days after TAVI. A percentage drop in platelet count (DPC) was determined from the pre- and lowest post-procedural values. RESULTS: SAPIEN 3 (S3) was implanted in 158 patients and Evolut PRO/PRO+ (Evolut) in 117. Both TAT and FDP increased after TAVI. Pre-TAVI balloon dilatation was generally performed on patients undergoing implantation with Evolut. Peak TAT was then stratified into 4 quartiles (Q1 to Q4). Of all 275 study patients, 69 patients reached ultra-hypercoagulation status (Q4). S3, TAVI without pre-balloon dilatation, DPC and bleeding complications were significantly associated with the ultra-hypercoagulation status after TAVI. TAT was significantly greater 1 h after S3 implantation than Evolut (median [IQR], 43.1 [34.1-59.6] vs. 31.0 [25.0-40.4] ng/mL; p < 0.001). In contrast, FDP levels did not differ between the two at any measurement point. The difference in DPC among the peak TAT quartiles was statistically significant (p < 0.001). The occurrence of bleeding complications was significantly higher in the group with ultra-hypercoagulation status (5.8% vs. 1.0%, p = 0.036). CONCLUSIONS: The increase in coagulation status and post-TAVI thrombocytopenia were significantly greater after S3 implantation. Ultra-hypercoagulation after TAVI was related to bleeding complications.

Perioperative changes in coagulation and platelet contribution to clot strength after transcatheter aortic valve implantation: A study using thromboelastography and conventional markers.

INTRODUCTION: Thrombotic and haemorrhagic complications have been reported following transcatheter aortic valve implantation (TAVI). However, few reports have studied perioperative changes in coagulation and platelet function after TAVI. Furthermore, there are no clear guidelines for antithrombotic therapy. This study aimed to examine the perioperative changes in coagulation and platelet contribution to clot strength after TAVI using thromboelastography (TEG 6s; Hemonetics). METHODS: This prospective observational study included 15 patients scheduled to undergo TAVI for severe aortic stenosis. TEG 6s global haemostasis was used to record three measurements: on the day of surgery (immediately before the operation) and postoperative days 1 and 3. The reaction time R to thrombosis; K and α, which represent the rate of thrombosis; and the maximum amplitude (MA) were measured from the kaolin thromboelastography (TEG) curves. The coagulation index (CI) was calculated from the measurement results to assess thrombotic tendency. In addition, MA was converted to elastic clot strength, and platelet function was assessed by the difference, Gp, in elastic strength depending on platelet activation. RESULTS: R and K decreased, and α tended to increase in kaolin TEG on days 1 and 3 after TAVI, indicating elevated coagulation function compared with the preoperative period, but MA and CI did not show significant changes. Gp decreased significantly on days 1 and 3, suggesting a decrease in the platelet contribution to clot strength. CONCLUSIONS: Compared with the preoperative period, coagulation tended to increase, and platelet contribution to clot strength decreased from days 1 to 3 after TAVI.

Validation of reliability and predictivity of membrane septum length measurements for pacemaker need after transcatheter aortic valve replacement.

OBJECTIVES: To assess the inter methodological agreement of membrane septum (MS) length measurement and additive value for risk stratification of new pacemaker implantation (PMI) over the established predictors after transcatheter aortic valve replacement (TAVR). BACKGROUND: Recent studies have suggested MS length and implantation depth (ID) as predictors for PMI after TAVR. However, the measurement of MS length is neither uniform nor validated in different cohort. METHODS: We retrospectively analyzed patients who underwent TAVR at five centers. The MS length was measured by two previously proposed methods (coronal and annular view method). Predictive ability of risk factors, including MS length and ID, for new PMI within 30 days after TAVR were evaluated. RESULTS: Among 754 patients of study population, 31 patients (4.1%) required new PMI within 30 days of TAVR. There was a weak correlation (ρ = 0.47) and a poor agreement between the two methods. The ID and the difference between MS length and ID (ΔMSID), were independent predictors for new PMI, whereas MS length alone was not. Further, for predicting new PMI after TAVR, discrimination performance was not significantly improved when MS length was added to the model with ID alone (integrated discrimination improvement = 0, p= 0.99; continuous net-reclassification improvement = 0.10, p= 0.62). CONCLUSIONS: External validity and predictive accuracy of MS length for PMI after TAVR were not sufficient to provide better risk stratification over the established predictors in our cohort. Moreover, the ID and ΔMSID, but not MS length alone, are predictive of future PMI after TAVR.

Effect of oral tolvaptan for 1 year in patients with functional mitral regurgitation.

The effect of the oral selective vasopressin V2-receptor antagonist tolvaptan for chronic phase therapy on patients with FMR remains unclear. We aimed to determine the efficacy of oral tolvaptan in patients with significant functional mitral regurgitation (FMR) to reduce the mortality and rehospitalization due to worsening heart failure (HF). We enrolled 219 patients (mean age 76 ± 9 years, 59.4% men) who were admitted at our hospital due to congestive HF during different two 1-year periods. The patients were divided into 2 groups: those who had significant FMR (MR ≥ grade 2 [n = 76]) and those who did not (MR < grade 2 [n = 143]) at discharge. The patients were further divided into a study group that received tolvaptan during follow-up and a control group that did not receive tolvaptan. We used an inverse probability of treatment weighting method with the primary end point defined as overall all-cause mortality and rehospitalization due to worsening HF within 1 year. Of the 76 patients with significant FMR at discharge, 2 of 20 (10%) who were administered tolvaptan died and 8 (40%) were readmitted to a hospital. Of the 56 patients who did not receive tolvaptan, 2 (3.5%) died and 18 (27.5%) required rehospitalization. After multiple adjustments, there were no significant differences for overall survival and rehospitalization between the groups (log-rank p = 0.700 and 0.510, respectively). Our results suggest that oral tolvaptan administration in addition to conventional diuretics had less impact on outcomes in patients with significant FMR.

Short-term dual anti-platelet therapy decreases long-term cardiovascular mortality after transcatheter aortic valve replacement.

No data are available on extended dual anti-platelet therapy (DAPT) duration which may influence long-term prognosis (later than 1 year) after transcatheter aortic valve replacement (TAVR). Therefore, this study is aimed to evaluate whether discontinuing DAPT within 1 year had an impact on adverse events after TAVR. Using data from the OCEAN-TAVI registry, we assessed 1008 patients who survived the first year after TAVR with DAPT since discharge. Patients were divided into 'DAPT group' (n = 462), comprising patients who took DAPT at both discharge and 1 year, and 'stop-DAPT group' (n = 546), comprising patients who took DAPT at discharge and single anti-platelet therapy (SAPT) at 1 year. We compared the incidence of cardiovascular (CV) death, major and minor bleeding, and ischemic stroke later than 1 year after TAVR between the two groups. A total of 28 CV deaths were observed later than 1 year after TAVR. The stop-DAPT group had a significantly lower incidence of CV death than the DAPT group (1.8% vs. 4.9%, log-rank P = 0.029). Stop DAPT was associated with lower CV death later than 1 year of TAVR in Cox regression analysis (adjusted hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.20-0.99), and in analysis with inverse probability of treatment weighting method using propensity score (adjusted HR, 0.45; 95% CI, 0.20-0.98). Our study demonstrated that switching from DAPT to SAPT within 1 year of TAVR was significantly associated with a lower CV death later than 1 year after TAVR.

Comparison of long-term mortality in patients who underwent transcatheter aortic valve replacement with or without anti-atherosclerotic therapy.

Atherosclerosis is a risk factor for both aortic stenosis (AS) and coronary artery disease. This study aimed to investigate whether anti-atherosclerotic therapy (AT), defined as the simultaneous use of antiplatelet agents, statins, and renin aldosterone system inhibitors, had long-term clinical benefits for patients who underwent transcatheter aortic valve replacement (TAVR). Between October 2013 and May 2017, 2518 patients (31% men; median age, 85 years) who underwent TAVR in 14 Japanese centers were divided into two groups: patients who were prescribed anti-atherosclerotic therapy (AT, n = 567) and patients who were not (no AT, n = 1951). The median follow-up period for this cohort was 693 days (interquartile range, 389-870 days). Compared to no AT group, AT group was associated with significantly lower 2-year all-cause mortality (11.7% vs. 16.5%; log-rank p = 0.002) and 2-year cardiovascular mortality rates (3.5% vs. 6.0%; log-rank p = 0.017). In a propensity-matched cohort (n = 495 each; median follow-up, 710 days [IQR, 394 - 896 days]), patients in AT group had a lower prevalence of 2-year cardiovascular mortality (3.8% vs. 6.2%, log-rank p = 0.024) than that in the no AT group. In the multivariate stepwise regression analysis, AT was a significant predictor of cardiovascular mortality (hazard ratio 0.45; 95% confidence interval 0.25-0.80; p = 0.007). AT may improve survival in post-TAVR patients. Future studies are necessary to identify an optimal treatment regimen to improve long-term outcomes after TAVR.

Predictor and Mid-Term Outcome of Clinically Significant Thrombocytopenia After Transcatheter Aortic Valve Selection.

BACKGROUND: The frequency and predictors of thrombocytopenia after transcatheter aortic valve implantation (TAVI) are unclear.Methods and Results:This study enrolled 342 patients undergoing TAVI (245 with a percutaneous transfemoral approach, 65 with transfemoral surgical cutdown, and 32 with a non-transfemoral approach). Balloon-expandable and self-expanding valves were implanted in 235 and 107 patients, respectively. Platelet counts started to drop immediately, reaching a nadir 2-4 days after TAVI. Clinically significant thrombocytopenia (CSTP) was defined as a platelet count ≤50×109/L at the time of the nadir or both a platelet count between 80 and 51×109/L and a decrease in platelet count ≥50%. CSTP occurred in 16.7% patients. Approach site and TAVI valve selection significantly predicted CSTP. In multivariate analysis, independent predictors of CSTP were liver cirrhosis (odds ratio [OR] 7.22; 95% confidence interval [CI] 1.05-49.82), baseline platelet count ≤120×109/L (OR 2.98; 95% CI 1.20-7.38), multiple blood transfusions (OR 4.03; 95% CI 1.72-9.41), and the use of balloon-expandable valves (OR 2.38; 95% CI 1.04-5.46). Kaplan-Meier survival analysis with a generalized Wilcoxon test revealed that mid-term (2 years) mortality was greater for patients with than without CSTP (31.4% vs. 15.5%; P=0.008). CONCLUSIONS: TAVI-related CSTP was not rare and was associated with poor mid-term outcomes. CSTP was not only caused by patients' comorbidities and TAVI complications, but also related to TAVI procedural factors.

1-Year Safety of 3-Month Dual Antiplatelet Therapy Followed by Aspirin or P2Y12 Receptor Inhibitor Monotherapy Using a Bioabsorbable Polymer Sirolimus-Eluting Stent.

BACKGROUND: This study evaluated the safety of 3-month dual antiplatelet therapy (DAPT) after implantation of a bioresorbable polymer sirolimus-eluting stent (BP-SES) and compared P2Y12inhibitor with aspirin monotherapy 3 months after DAPT.Methods and Results:Patients who underwent percutaneous coronary intervention using BP-SES were enrolled and followed for 1 year. Patients with a history of stent thrombosis were excluded. The primary endpoint was a composite of all-cause death, myocardial infarction, stroke (ischemic and hemorrhagic), definite or probable stent thrombosis, and severe bleeding at 12 months. The BP-SES arm of the CENTURY II trial was used as a conventional DAPT group for comparison. After DAPT, patients were maintained on either aspirin (n=846) or a P2Y12inhibitor (n=674 patients).In all, 1,695 patients were enrolled in the study across 65 centers. The primary endpoint occurred in 4.3% of patients at 1 year. After propensity score adjustment, the incidence of the primary endpoint was not inferior in those receiving DAPT for 3 months compared with conventional DAPT (5.5%; Pnon-inferiority<0.0001). The incidence of the primary endpoint and severe bleeding did not differ between the aspirin and P2Y12inhibitor monotherapy groups. CONCLUSIONS: After adjustment, 3-month DAPT was not inferior to longer DAPT after BP-SES implantation in terms of net adverse clinical events. There was no difference in bleeding and thrombotic events between P2Y12inhibitor and aspirin monotherapy after 3 months DAPT.

Predictive value of the geriatric nutritional risk index in percutaneous coronary intervention with rotational atherectomy.

The prognostic value of the geriatric nutritional risk index (GNRI) in patients undergoing percutaneous coronary intervention (PCI) with rotational atherectomy (RA) remains unknown. Therefore, we aimed to clarify whether the GNRI could predict major adverse cardiac events (MACE) in patients undergoing PCI with RA. A total of 206 patients who underwent PCI with RA from January 2009 to December 2017 were retrospectively tracked. The patients were divided into 2 groups based on the GNRI value on admission. MACE comprised all-cause death, target lesion revascularization (TLR), target vessel revascularization (TVR), and myocardial infarction. One year of follow up was completed in 95.6% of patients. During this period, 50 cases of MACE were observed (all-cause death, 32 cases; TLR, 21 cases; and TVR, 2 cases). Patients with a low GNRI (< 98) had a significantly higher incidence of MACE than did patients with a high GNRI (≥ 98) (37.9% vs. 15.5%, log-rank p < 0.05). The GNRI was an independent predictor of MACE (hazard ratio, 0.94; 95% confidence interval [CI], 0.92-0.97). Furthermore, the GNRI had better predictive power than did its components alone (i.e. body mass index and serum albumin level) (net-reclassification improvement, 0.39; 95% CI, 0.07-0.71; p = 0.01; integrated discrimination improvement, 0.02; 95% CI, - 0.01-0.04; p = 0.07). The GNRI on admission is a predictor of MACE after PCI with RA. Further studies are required to determine whether intensive medical therapy could improve clinical events, particularly cardiovascular death and revascularization, in this population.

Clinical safety and efficacy of tolvaptan for acute phase therapy in patients with low-flow and normal-flow severe aortic stenosis.

Conventional diuretic therapy for low-flow (LF) severe aortic stenosis (SAS) often has an inadequate effect or causes hemodynamic instability. Tolvaptan is used for acute heart failure in addition to conventional diuretics, and it does not cause intravascular dehydration. This study aimed to retrospectively investigate the safety and efficacy of tolvaptan in the acute phase in 56 consecutive patients with SAS and compared LF-SAS with normal-flow (NF) SAS. The primary endpoints were adverse clinical events (death, worsening heart failure, worsening renal failure, fatal arrhythmia, cardiogenic or hypovolemic shock, and use of inotropic agents) and the volume of urine within 48 h of tolvaptan administration. Among 56 patients, 16 had LF-SAS (29%), and 40 had NF-SAS (71%). Severe adverse clinical events were not observed 48 h after tolvaptan administration. In both groups, the urine volume significantly increased after tolvaptan administration in comparison to 24 h before tolvaptan administration (both, p < 0.01). There were no changes in the urine volume during the initial 24 and 48 h. In the LF-SAS group, tolvaptan resulted in a significant decrease in fluid balance during the initial 24 and 48 h compared to 24 h before tolvaptan administration (p < 0.05). Adding tolvaptan to conventional treatment is safe and effective without renal dysfunction and hypotension in patients with SAS, including those with LF.

Association between valvuloarterial impedance after transcatheter aortic valve implantation and 2-year mortality in elderly patients with severe symptomatic aortic stenosis: the OCEAN-TAVI registry.

Pre-procedural valvuloarterial impedance (Zva) is considered as a useful predictor of mortality in patients diagnosed as having severe aortic stenosis (AS) who undergo transcatheter aortic valve implantation (TAVI). However, the prognostic significance of post-procedural Zva remains unclear. We aimed to evaluate the prognostic significance of Zva after TAVI. We retrospectively analyzed the clinical and echocardiographic data of 1004 consecutive elderly patients (median 84 years old, 27.5% men) who underwent TAVI for severe symptomatic AS. Zva was calculated after TAVI, and patients were divided into three groups based on tertile values: the high [> 3.33 (n = 335)], intermediate [2.49-3.33 (n = 334)], and low Zva groups [< 2.49 (n = 335)]. The estimated 2-year all-cause and cardiovascular mortalities using Kaplan-Meier analysis were 16.2% [95% confidence interval (CI) 11.8-20.4] and 5.9% (95% CI 3.2-8.6), respectively. There were no significant intergroup differences in each endpoint (long-rank p = 0.518 for all-cause mortality, p = 0.757 for cardiovascular mortality). Multivariable Cox regression analyzes with adjustments of patient characteristics and medications showed that the post-procedural Zva was not associated with the 2-year all-cause mortality [intermediate Zva group versus (vs.) low Zva group: adjusted hazard ratio (aHR) = 1.34, 95% CI 0.75-2.40, p = 0.316; high Zva group vs. low Zva group: aHR = 1.17, 95% CI 0.64-2.16, p = 0.613] and cardiovascular mortality (intermediate Zva group vs. low Zva group: aHR = 1.50, 95% CI 0.56-4.06, p = 0.421; high Zva group vs. low Zva group: aHR = 1.25, 95% CI 0.43-3.65, p = 0.682). Our results suggest that post-procedural Zva was not associated with 2-year all-cause or cardiovascular mortalities in patients with severe symptomatic AS who underwent TAVI.

The MAGGIC risk score predicts mortality in patients undergoing transcatheter aortic valve replacement: sub-analysis of the OCEAN-TAVI registry.

This study is aimed to evaluate the performance of MAGGIC risk score for predicting mortality by external validation using multicenter transcatheter aortic valve replacement (TAVR) registry. We assessed 1383 patients who underwent TAVR from October 2013 to April 2016. Patients were divided into 2 groups according to the median of MAGGIC score and we compared the incidence of all-cause death between high and low MAGGIC score. To assess whether the MAGGIC risk score add prognostic value on STS risk score, we also compared the incidence of all-cause death between the 2 groups according to low, intermediate, and high STS score. The median of MAGGIC score was 29 (interquartile range: 13-46). Within 2 years, 147 cases of all-cause death were observed. The high MAGGIC (30-46) risk score was significantly associated with an increased risk of all-cause death as compared to low MAGGIC (11-29) risk score and this relationship was also observed in patients with high STS risk score. However, this relationship was not observed in patients with low and intermediate STS score. Multivariate analysis showed that the MAGGIC risk score was an independent predictor of all-cause death (hazard ratio, 1.07; 95% confidence interval, 1.03-1.11). Our results demonstrated that the MAGGIC score predicts all-cause death in TAVR population and provides better risk stratification, particularly in patients with high STS risk.

Risk stratification using lean body mass in patients undergoing transcatheter aortic valve replacement.

BACKGROUND: The prognostic impact of skeletal muscle mass, assessed using lean body mass (LBM), remain unclear in patients who underwent transcatheter aortic valve replacement (TAVR). The aim of this study to assess prognostic impact of LBM on mortality after TAVR. METHODS: We assessed 1,613 patients (median age 85 years, 70% female) who underwent TAVI from October 2013 to April 2016 using OCEAN (Optimized transCathEter vAlvular interveNtion)-TAVI registry data. LBM was calculated using the James formula. The primary endpoint was all-cause death after TAVR. RESULTS: Median follow-up period was 287 days (interquartile range 110-462). The Kaplan-Meier analysis demonstrated that patients with low LBM had significantly higher incidence of all-cause death than those with high LBM in male (32.3% vs. 9.9%, log rank P < 0.001) and female (15.8% vs. 9.2%, log-rank P = 0.011). On contrary, the risk stratification using body mass index (BMI) could not validate into female patients who underwent TAVR. The multivariate analysis showed that the LBM was an independent predictor of all-cause death in male (Hazard ratio [HR] 0.93; 95% confidence interval [CI] 0.89-0.98) and female (HR 0.94; 95% CI 0.89-0.99). Inversely, the assessment using BMI could not identify the high-risk population in a female. CONCLUSIONS: The patients with low LBM had the higher incidence of all-cause death after TAVR than those with high LBM, regardless of gender. Thus, the risk stratification using LBM might provide further insight to identify the high-risk TAVR population, compared to conventional risk stratification using BMI.

Comparison of midterm outcomes of transcatheter aortic valve implantation in patients with and without previous coronary artery bypass grafting.

The midterm safety and feasibility of transcatheter aortic valve implantation (TAVI) for patients with a history of coronary artery bypass graft (CABG) and high operative risk are unclear. This study compared the midterm outcomes of patients undergoing TAVI with or without previous CABG surgery. Between October 2013 and July 2016, 1,613 patients underwent TAVI according to the Optimized CathEter vAlvular iNtervention (OCEAN)-TAVI registry (previous CABG: n = 120; no previous CABG: n = 1493). The propensity score comprised the variables of the Society of Thoracic Surgeons Score, previous myocardial infarction, peripheral artery disease, chronic kidney disease > stage 2 (estimated glomerular filtration rate < 60 mL/min/1.73 m2), and the TAVI approach method. After propensity matching, 118 patients were classified into the CABG and non-CABG groups. Kaplan-Meier analysis revealed that the incidence of overall cardiovascular death in the CABG group was significantly higher than in the non-CABG group (log-rank; p = 0.004). Overall mortality due to heart failure was higher in the CABG than in the non-CABG group (8.5 vs. 1.7%, p = 0.038). The present study demonstrated that patients with a history of CABG who underwent TAVI had a higher frequency of cardiovascular death, mainly due to heart failure. Heart failure detection and rigorous heart failure management are required after TAVI.

Incidence, Predictors, and Midterm Clinical Outcomes of Myocardial Injury After Transcatheter Aortic-Valve Implantation.

Our aim was to assess the clinical effects of myocardial injury after transcatheter aortic-valve implantation (TAVI). Between October 2013 and July 2016, 157 patients underwent TAVI with Sapien XT, Sapien 3, or CoreValve prostheses at our institute. Of these, 130 patients for whom the transapical approach was not used were included in this study. Myocardial injury was defined as a peak troponin I level of ≥1.5 ng/mL within 48 hours after TAVI. We evaluated the predictors of myocardial injury and compared the clinical outcomes of 82 patients classified as the myocardial injury group and 44 patients classified as the non-myocardial injury group. The patients were aged 85 ± 6 years. Myocardial injury occurred in 82 patients (65.1%). Age (per 1 increase) (odds ratio [OR]: 1.11, 95% confidence interval [CI]: 1.01-1.22, P = 0.041), female sex (OR: 3.88, 95% CI: 1.23-12.22, P = 0.021), valve type (Sapien XT; OR: 4.22, 95% CI: 1.15-15.47, P = 0.03, Core valve; OR: 18.12, 95% CI: 2.86-114.59, P = 0.002), balloon aortic valvuloplasty as a bridge therapy (OR: 0.10, 95% CI: 0.02-0.42, P = 0.002), and left ventricular end-diastolic volume (LVEDV) (per 1 increase) (OR: 0.97, 95% CI: 0.95-0.99, P = 0.003) were associated with myocardial injury in a multivariate model. The myocardial injury group did not have a higher rate of midterm (365-day) mortality (log-rank test P = 0.57) than the non-myocardial injury group on Kaplan-Meier analysis. Myocardial injury after TAVI was not associated with midterm mortality.

Impact of deteriorated calcium-phosphate homeostasis on amputation-free survival after endovascular revascularization in patients with critical limb ischemia on hemodialysis.

Patients on hemodialysis (HD) have abnormalities of calcium-phosphate (CaP) homeostasis and high CaP product contributes to atherosclerosis pathogenesis and adverse events. Patients on HD with critical limb ischemia (CLI) are at risk for major amputation and death because of advanced systemic atherosclerotic disease. The aim of this study was to evaluate the relationship between CaP product and amputation-free survival (AFS) in CLI after endovascular treatment (EVT). We retrospectively analyzed 221 CLI patients on HD. In Kaplan-Meier analysis, AFS was significantly lower in patients with CaP product ⩾ 55 mg(2)/dL(2) compared to those with CaP product <55 mg(2)/dL(2) (54.3% vs 78.5%, p = 0.002). However, neither serum phosphate nor calcium levels were individually associated with AFS. In multivariate analysis, CaP product ⩾ 55 mg(2)/dL(2) was an independent predictor for AFS in CLI patients on HD (hazard ratio, 3.03; 95% confidence interval, 1.78-5.15; p-value < 0.001). We concluded abnormal CaP homeostasis was associated with lower AFS after EVT in CLI patients on HD, and can serve for their risk stratification.

Impact of oral beta-blocker therapy on mortality after primary percutaneous coronary intervention for Killip class 1 myocardial infarction.

The use of beta-blockers therapy has been recommended to reduce mortality in patients with left ventricular dysfunction after acute myocardial infarction (AMI). Primary percutaneous coronary intervention (PCI), which has become the mainstay of treatment for AMI, is associated with a lower mortality than fibrinolysis. The benefits of beta-blockers after primary PCI in AMI patients without pump failure are unclear. We hypothesized that oral beta-blocker therapy after primary PCI might reduce the mortality in AMI patients without pump failure. The assessment of lipophilic vs. hydrophilic statin therapy in acute myocardial infarction (ALPS-AMI) study was a multi-center study that enrolled 508 AMI patients to compare the efficacy of hydrophilic and lipophilic statins in secondary prevention after myocardial infarction. We prospectively tracked cardiovascular events for 3 years in 444 ALPS-AMI patients (median age 66 years; 18.2 % women) who had Killip class 1 on admission and were discharged alive. The primary endpoint was all-cause mortality. The 3-year follow-up was completed in 413 patients (93.0 %). During this follow-up, 21 patients (4.7 %) died. In Kaplan-Meier analysis, patients on beta-blockers had a significantly lower incidence of all-cause mortality (2.7 vs. 7.3 %, log-rank p = 0.025). After adjusting for the calculated propensity score for using beta-blockers, their use remained an independent predictor of all-cause mortality (hazard ratio 0.309; 95 % confidence interval 0.116-0.824; p = 0.019). In the statin era, the use of beta-blocker therapy after primary PCI is associated with lower mortality in AMI patients with Killip class 1 on admission.

Comparison of Inflammatory Biomarkers in Outpatients With Prior Myocardial Infarction.

Inflammatory biomarkers have been proposed for use in the risk stratification of patients with acute myocardial infarction (AMI). We examined the value of inflammatory biomarkers over clinical features for predicting cardiovascular (CV) events in stable outpatients with MI. We enrolled 430 post-MI patients and measured their levels of high-sensitivity C reactive protein (hs-CRP), growth differentiation factor-15 (GDF-15), and the interleukin-1 receptor family member called ST2 (ST2), one month after AMI. Patients were prospectively followed for 3 years. In our study cohort (mean age, 66 ± 12 years; left ventricular ejection fraction, 55 ± 13%), CV events were observed in 39 patients (9.1%). Kaplan- Meier analysis revealed that patients with high levels of GDF-15 (≥ 1221.0 ng/L) showed poorer prognoses than those with low levels of GDF-15 (< 1221.0 ng/L) (20.4% versus 3.6%, P < 0.001); hs-CRP and ST2 did not show a similar correlation with prognoses. GDF-15 remained associated with CV events after adjusting for age, chronic kidney disease, and B-type natriuretic peptide (hazard ratio, 1.001; 95% confidence interval, 1.000 - 1.001; P = 0.046). GDF-15 provided an incremental predictive value for CV events over clinical features (incremental value in global χ(2) = 43.81, P < 0.001). In outpatients with prior MI, GDF-15 was an independent indicator of CV events, unlike hs-CRP and ST2. GDF15 provided an incremental prognostic value over clinical features.

Prognostic Significance of Neuroadrenergic Dysfunction for Cardiovascular Events in Patients With Acute Myocardial Infarction.

BACKGROUND: The dysregulation of systemic blood pressure (BP) variation or cardiac neuroadrenergic dysfunction is associated with adverse cardiovascular events. We aimed to clarify the prognostic significance of neuroadrenergic dysfunction for cardiovascular events in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: We enrolled 63 AMI patients (mean age, 67±12 years) underwent ambulatory BP monitoring (ABPM) and cardiac iodine-(123)metaiodobenzylguanidine (MIBG) imaging within 4 weeks after AMI onset. We analyzed the circadian BP pattern and heart-to-mediastinum (H/M) MIBG uptake ratio. All the patients were followed for 2 years. The study endpoint was a composite of major adverse cardiovascular events, including all-cause death, MI, coronary revascularization except for the MI culprit lesion, and stroke. Patients with a non-dipper pattern (n=29) or an H/M ratio <1.96 (n=28) had a worse prognosis than those with either a dipper pattern (n=34) or an H/M ratio ≥1.96 (n=35; log-rank, P=0.013 and 0.010, respectively). Patients with both a non-dipper pattern and an H/M ratio <1.96 (n=12) had a significantly worse prognosis than did the other patients (P=0.0020). CONCLUSIONS: Dysregulation of BP variation and cardiac MIBG uptake were associated with cardiovascular events following AMI. Examining ABPM with MIBG imaging may potentially improve risk stratification in these patients.