Cardiac Myosin Activation with Omecamtiv Mecarbil in Systolic Heart Failure.

BACKGROUND: The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS: We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS: During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS: Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016-002299-28.).

Cardiac Troponin and Treatment Effects of Omecamtiv Mecarbil: Results From the GALACTIC-HF Study.

BACKGROUND: Omecamtiv mecarbil improves outcomes in patients with heart failure and reduced ejection fraction (HFrEF). We examined the relationship between baseline troponin levels, change in troponin levels over time and the treatment effect of omecamtiv mecarbil in patients enrolled in the Global Approach to Lowering Adverse Cardiac Outcomes through Improving Contractility in Heart Failure (GALACTIC-HF) trial (NCT02929329). METHODS: GALACTIC-HF was a double-blind, placebo-controlled trial that randomized 8256 patients with symptomatic HFrEF to omecamtiv mecarbil or placebo. High-sensitivity troponin I (cTnI) was measured serially at a core laboratory. We analyzed the relationship between both baseline cTnI and change in cTnI concentrations with clinical outcomes and the treatment effect of omecamtiv mecarbil. RESULTS: Higher baseline cTnI concentrations were associated with a risk of adverse outcomes (hazard ratio for the primary endpoint of time to first HF event or CV death = 1.30; 95% CI 1.28, 1.33; P < 0.001 per doubling of baseline cTnI). Although the incidence of safety outcomes was higher in patients with higher baseline cTnI, there was no difference between treatment groups. Treatment with omecamtiv mecarbil led to a modest increase in cTnI that was related to plasma concentrations of omecamtiv mecarbil, and it peaked at 6 weeks. An increase in troponin from baseline to week 6 was associated with an increased risk of the primary endpoint (P < 0.001), which was similar, regardless of treatment assignment (P value for interaction = 0.2). CONCLUSIONS: In a cohort of patients with HFrEF, baseline cTnI concentrations were strongly associated with adverse clinical outcomes. Although cTnI concentrations were higher in patients treated with omecamtiv mecarbil, we did not find a differential effect of omecamtiv mecarbil on either safety or efficacy based on baseline cTnI status or change in cTnI.

Chronic Effects of Adaptive Servo-Ventilation Therapy on Mortality and the Urgent Rehospitalization Rate in Patients Experiencing Recurrent Admissions for Heart Failure　- A Multicenter Prospective Observational Study (SAVIOR-L).

BACKGROUND: This study investigated whether the chronic use of adaptive servo-ventilation (ASV) reduces all-cause mortality and the rate of urgent rehospitalization in patients with heart failure (HF).Methods and Results: This multicenter prospective observational study enrolled patients hospitalized for HF in Japan between 2019 and 2020 who were treated either with or without ASV therapy. Of 845 patients, 110 (13%) received chronic ASV at hospital discharge. The primary outcome was a composite of all-cause death and urgent rehospitalization for HF, and was observed in 272 patients over a 1-year follow-up. Following 1:3 sequential propensity score matching, 384 patients were included in the subsequent analysis. The median time to the primary outcome was significantly shorter in the ASV than in non-ASV group (19.7 vs. 34.4 weeks; P=0.013). In contrast, there was no significant difference in the all-cause mortality event-free rate between the 2 groups. CONCLUSIONS: Chronic use of ASV did not impact all-cause mortality in patients experiencing recurrent admissions for HF.

Long-Term Treatment With Sacubitril/Valsartan in Japanese Patients With Chronic Heart Failure and Reduced Ejection Fraction　- Open-Label Extension of the PARALLEL-HF Study.

BACKGROUND: The PARALLEL-HF study assessed the efficacy and safety of sacubitril/valsartan vs. enalapril in Japanese patients with chronic heart failure with reduced ejection fraction (HFrEF). This open-label extension (OLE) assessed long-term safety with sacubitril/valsartan.Methods and Results: This study enrolled 150 patients who received sacubitril/valsartan 50 or 100 mg, b.i.d., in addition to optimal background heart failure (HF) therapy. A dose level of sacubitril/valsartan 200 mg, b.i.d., was targeted by Week 8. At OLE baseline, higher concentrations of B-type natriuretic peptide (BNP) and urine cGMP, and lower concentrations of N-terminal pro B-type natriuretic peptide (NT-proBNP), were observed in the sacubitril/valsartan core group (patients who received sacubitril/valsartan in both the core and extension study) than in the enalapril core group (patients who received enalapril in the core study and were then transitioned to sacubitril/valsartan). The mean exposure to study drug was 98.9%. There was no trend of worsening of HF at Month 12. No obvious changes in cardiac biomarkers were observed, whereas BNP and urine cGMP increased and NT-proBNP decreased in the enalapril core group, which was evident at Weeks 2-4 and sustained to Month 12. CONCLUSIONS: Long-term sacubitril/valsartan at doses up to 200 mg, b.i.d., has a positive risk-benefit profile; it was safe and well tolerated in Japanese patients with chronic HFrEF.

Efficacy and Safety of Sacubitril/Valsartan in Japanese Patients With Heart Failure According to Baseline Systolic Blood Pressure　- Results From a Subgroup Analysis of the PARALLEL-HF Study.

BACKGROUND: Lower systolic blood pressure (SBP) is known to be associated with poor prognosis in heart failure (HF). We evaluated the efficacy and safety of sacubitril/valsartan according to baseline SBP tertiles in Japanese patients from the PARALLEL-HF study.Methods and Results: In all, 223 patients were stratified into tertiles according to baseline SBP (≤114 mmHg: n=75; >114 and ≤130 mmHg: n=76; and >130 mmHg: n=72). Patients with lower SBP (≤114 mmHg) had the highest median N-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations at baseline (P=0.0184). No significant difference was observed between sacubitril/valsartan and enalapril for the composite outcome of cardiovascular death and HF hospitalization across SBP tertiles (P-interaction=0.2682). Although the P-interaction value was not significant (0.2106), a greater reduction in NT-proBNP with sacubitril/valsartan compared with enalapril was observed in patients with SBP >130 mmHg (P=0.0076). The incidence of hypotension-related events and reduction or discontinuation of treatment due to hypotension-related events was higher in the lower SBP subgroup, and these events were more frequent in the sacubitril/valsartan than enalapril group. CONCLUSIONS: The efficacy of sacubitril/valsartan compared with enalapril was consistent across baseline SBP tertiles in Japanese patients from the PARALLEL-HF study. Hypotension-related events were more common in patients treated with sacubitril/valsartan with lower SBP.

Sex differences in the prevalence and prognostic impact of physical frailty and sarcopenia among older patients with heart failure.

BACKGROUND AND AIMS: Frailty and sarcopenia are common and confer poor prognosis in elderly patients with heart failure; however, gender differences in its prevalence or prognostic impact remain unclear. METHODS AND RESULTS: We included 1332 patients aged ≥65 years, who were hospitalized for heart failure. Frailty and sarcopenia were defined using the Fried phenotype model and Asian Working Group for Sarcopenia criteria, respectively. Gender differences in frailty and sarcopenia, and interactions between sex and prognostic impact of frailty/sarcopenia on 1-year mortality were evaluated. Overall, 53.9% men and 61.0% women and 23.7% men and 14.0% women had frailty and sarcopenia, respectively. Although sarcopenia was more prevalent in men, no gender differences existed in frailty after adjusting for age. On Kaplan-Meier analysis, frailty and sarcopenia were significantly associated with 1-year mortality in both sexes. On Cox proportional hazard analysis, frailty was associated with 1-year mortality only in men, after adjusting for confounding factors (hazard ratio [HR], 1.94; 95% confidence interval [CI], 1.19-3.16; P = 0.008 for men; HR, 1.63; 95% CI, 0.84-3.13; P = 0.147 for women); sarcopenia was an independent prognostic factor in both sexes (HR, 1.93; 95% CI, 1.13-3.31; P = 0.017 for men; HR, 3.18; 95% CI, 1.59-5.64; P = 0.001 for women). There were no interactions between sex and prognostic impact of frailty/sarcopenia (P = 0.806 for frailty; P = 0.254 for sarcopenia). CONCLUSIONS: Frailty and sarcopenia negatively affect older patients with heart failure from both sexes. CLINICAL TRIALS: This study was registered at the University Hospital Information Network (UMIN-CTR, unique identifier: UMIN000023929) before the first patient was enrolled.

Prognostic impact of malnutrition in elderly patients with acute myocardial infarction.

We aimed to investigate the prevalence and the prognostic impact of malnutrition using the geriatric nutritional risk index (GNRI) in elderly patients with acute myocardial infarction (AMI). We investigated 130 consecutive patients aged ≥ 75 years who were discharged following successful primary coronary intervention between March 2009 and December 2016. The mean age of the patients was 81.5 ± 5.0 years, and 55.4% of them were male. At discharge, the patients' nutritional statuses were evaluated using the GNRI, which were calculated as follows: 14.89 × serum albumin (g/dL) + 41.7 × body mass index/22. The patients were divided into two groups, a low GNRI group (GNRI < 92) with nutrition-related risk and a high GNRI group (GNRI ≥ 92) without nutrition-related risk. The mean GNRI score of all patients was 95.2 ± 11.0, and 46 patients (35.4%) had a low GNRI score. During the mean follow-up of 1030 ± 850 days, the all-cause mortality was significantly higher in the low GNRI group than in the high GNRI group (32.6% vs. 13.1%, p < 0.001), while the event rates of AMI recurrence and hospitalization due to heart failure did not differ significantly between the two groups. Multivariate Cox proportional analysis revealed that low GNRI was a modest but independent predictor of mortality (hazard ratio, 0.94; 95% confidence interval 0.90-0.98; p = 0.01). Among elderly patients with AMI, malnutrition assessed using the GNRI was often encountered and was an independent predictor of long-term mortality.

Sarcopenic obesity is associated with impaired physical function and mortality in older patients with heart failure: insight from FRAGILE-HF.

BACKGROUND: The purpose of this study was to clarify the prevalence, association with frailty and exercise capacity, and prognostic implication of sarcopenic obesity in patients with heart failure. METHODS: The present study included 779 older adults hospitalized with heart failure (median age: 81 years; 57.4% men). Sarcopenia was diagnosed based on the guidelines by the Asian Working Group for Sarcopenia. Obesity was defined as the percentage of body fat mass (FM) obtained by bioelectrical impedance analysis. The FM cut-off points for obesity were 38% for women and 27% for men. The primary endpoint was 1-year all-cause death. We assessed the associations of sarcopenic obesity occurrence with the short physical performance battery (SPPB) score and 6-minute walk distance (6MWD). RESULTS: The rates of sarcopenia and obesity were 19.3 and 26.2%, respectively. The patients were classified into the following groups: non-sarcopenia/non-obesity (58.5%), non-sarcopenia/obesity (22.2%), sarcopenia/non-obesity (15.3%), and sarcopenia/obesity (4.0%). The sarcopenia/obesity group had a lower SPPB score and shorter 6MWD, which was independent of age and sex (coefficient, - 0.120; t-value, - 3.74; P < 0.001 and coefficient, - 77.42; t-value, - 3.61; P < 0.001; respectively). Ninety-six patients died during the 1-year follow-up period. In a Cox proportional hazard analysis, sarcopenia and obesity together were an independent prognostic factor even after adjusting for a coexisting prognostic factor (non-sarcopenia/non-obesity vs. sarcopenia/obesity: hazard ratio, 2.48; 95% confidence interval, 1.22-5.04; P = 0.012). CONCLUSION: Sarcopenic obesity is a risk factor for all-cause death and low physical function in older adults with heart failure. TRIAL REGISTRATION: University Hospital Information Network (UMIN-CTR: UMIN000023929 ).

Efficacy and Safety of Sacubitril/Valsartan in Japanese Patients With Chronic Heart Failure and Reduced Ejection Fraction　- Results From the PARALLEL-HF Study.

BACKGROUND: In the Prospective Comparison of angiotensin receptor neprilysin inhibitor (ARNI) With ACEi to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) study, treatment with sacubitril/valsartan reduced the primary outcome of cardiovascular (CV) death and heart failure (HF) hospitalization compared with enalapril in patients with chronic HF and reduced ejection fraction (HFrEF). A prospective randomized trial was conducted to assess the efficacy and safety of sacubitril/valsartan in Japanese HFrEF patients.Methods and Results:In the Prospective comparison of ARNI with ACEi to determine the noveL beneficiaL trEatment vaLue in Japanese Heart Failure patients (PARALLEL-HF) study, 225 Japanese HFrEF patients (New York Heart Association [NYHA] class II-IV, left ventricular ejection fraction [LVEF] ≤35%) were randomized (1 : 1) to receive sacubitril/valsartan 200 mg bid or enalapril 10 mg bid. Over a median follow up of 33.9 months, no significant between-group difference was observed for the primary composite outcome of CV death and HF hospitalization (HR 1.09; 95% CI 0.65-1.82; P=0.6260). Early and sustained reductions in N-terminal pro-brain natriuretic peptide (NT-proBNP) from baseline were observed with sacubitril/valsartan compared with enalapril (between-group difference: Week 2: 25.7%, P<0.01; Month 6: 18.9%, P=0.01, favoring sacubitril/valsartan). There was no significant difference in the changes in NYHA class and Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score at Week 8 and Month 6. Sacubitril/valsartan was well tolerated with fewer study drug discontinuations due to adverse events, although the sacubitril/valsartan group had a higher proportion of patients with hypotension. CONCLUSIONS: In Japanese patients with HFrEF, there was no difference in reduction in the risk of CV death or HF hospitalization between sacubitril/valsartan and enalapril, and sacubitril/valsartan was safe and well tolerated.

Comparison of clinical outcomes and left ventricular remodeling after ST-elevation myocardial infarction between patients with and without diabetes mellitus.

Left ventricular remodeling (LVR) after ST-elevation myocardial infarction (STEMI) is generally thought to be an adaptive but compromising phenomenon particularly in patients with diabetes mellitus (DM). However, whether the extent of LVR is associated with poor prognostic outcome with or without DM after STEMI in the modern era of reperfusion therapy has not been elucidated. This was a single-center retrospective observational study. Altogether, 243 patients who were diagnosed as having STEMI between January 2016 and March 2019, and examined with echocardiography at baseline (at the time of index admission) and mid-term (from 6 to 11 months after index admission) follow-up were included and divided into the DM (n = 98) and non-DM groups (n = 145). The primary outcome was major adverse cardiovascular events (MACEs) defined as the composite of all-cause death, heart failure (HF) hospitalization, and non-fatal myocardial infarction. The median follow-up duration was 621 days (interquartile range: 304-963 days). The DM group was significantly increased the rate of MACEs (P = 0.020) and HF hospitalization (P = 0.037) compared with the non-DM group, despite of less LVR. Multivariate Cox regression analyses revealed that the patients with DM after STEMI were significantly associated with MACEs (Hazard ratio [HR] 2.79, 95% confidence interval [CI] 1.20-6.47, P = 0.017) and HF hospitalization (HR 3.62, 95% CI 1.19-11.02, P = 0.023) after controlling known clinical risk factors. LVR were also significantly associated with MACEs (HR 2.44, 95% CI 1.03-5.78, P = 0.044) and HF hospitalization (HR 3.76, 95% CI 1.15-12.32, P = 0.029). The patients with both DM and LVR had worse clinical outcomes including MACEs and HF hospitalization, suggesting that it is particularly critical to minimize LVR after STEMI in patients with DM.

Usefulness of 500-m walk electrocardiogram test on clinical outcomes in patients with ST-segment elevation myocardial infarction.

The current Japanese guideline for ST-segment elevation myocardial infarction (STEMI) recommends 500-m walk electrocardiogram (ECG) test for patients with STEMI during hospitalization. However, little is known regarding the association between acute phase 500-m walk ECG test and clinical outcomes. The purpose of this study was to investigate the association between 500-m walk ECG test and mid-term clinical outcomes in patients with STEMI. A total of 313 STEMI patients who underwent primary percutaneous coronary interventions were included, and were divided into the successful 500-m group (n = 263) and the unsuccessful 500-m group (n = 50). The primary endpoint was the major adverse cardiovascular events (MACE), which were defined as the composite of all cause death, acute myocardial infarction, readmission for heart failure, and ischemia-driven target vessel revascularization (TVR). During the follow-up period (median 223 days), a total of 55 MACE were observed. The log-rank test revealed that MACE, all cause death, readmission for heart failure, and ischemia-driven TVR were more frequently observed in the unsuccessful 500-m group than the successful 500-m group. In the multivariate Cox proportional hazard model, the unsuccessful 500-m walk ECG test was significantly associated with MACE (OR 5.62, 95% CI 3.08-10.08, P < 0.01) after controlling confounding factors such as age, and serum creatinine levels. In conclusion, the unsuccessful 500-m walk ECG test was significantly associated with poor mid-term outcomes in patients with STEMI. Our results suggest the usefulness of 500-m walk ECG test to stratify the high-risk group from patients with STEMI.

Association of Baseline Anemia with Mid-Term Clinical Outcomes in Patients Who Underwent Trans-Radial Primary Percutaneous Coronary Intervention.

Radial access is recommended for primary percutaneous coronary intervention (PCI), because it has fewer bleeding complications than trans-femoral PCI. However, even if trans-radial PCI is chosen, patients with ST-elevation myocardial infarction (STEMI) presenting with anemia on admission might have poor clinical outcomes. The aim of this retrospective study was to investigate whether anemia on admission was associated with mid-term clinical outcomes in patients who underwent trans-radial primary PCI. The primary endpoint was a composite of all-cause death, recurrent acute myocardial infarction, and readmission for heart failure. A total of 288 consecutive patients with STEMI who underwent trans-radial primary PCI were divided into an anemia group (n = 79) and a non-anemia group (n = 209). The median follow-up duration was 301 days. The anemia group was significantly older than the non-anemia group (77.3 ± 11.9 versus 64.4 ± 12.7 years, respectively; P < 0.001). There were significantly more females in the anemia group than in the non-anemia group (36.7% versus 14.4%, respectively; P < 0.001). Kaplan-Meier analysis revealed that the composite outcome-free survival was significantly worse in the anemia group than in the non-anemia group (P < 0.001). Multivariate Cox hazard model analysis revealed that hemoglobin levels on admission were significantly associated with the composite outcome (per 1 g/dL increase: hazard ratio 0.76, 95% confidence interval 0.66-0.88, P < 0.001) after controlling for confounding factors. In conclusion, baseline anemia was significantly associated with poor clinical outcomes. Patients with STEMI presenting with anemia should be managed carefully, even if trans-radial primary PCI is chosen.

Comparison of Clinical Characteristics of Acute Myocardial Infarction Between Young (< 55 Years) and Older (55 to < 70 Years) Patients.

Although the incidence of acute myocardial infarction (AMI) has been decreasing in the elderly, it has been increasing in the young, especially in Japan. A social impact of AMI would be greater in the young, because loss of the young directly influences social activities such as business, child-raising, and tax payment. The aim of this study was to identify the specific characteristics of young AMI patients. We retrospectively included 408 consecutive AMI patients < 70 years of age, divided into a young group (< 55 years: n = 136) and an older group (55 to < 70 years: n = 272). The prevalence of overweight was greater in the young group (58.5%) than in the older group (40.7%) (P = 0.001). The frequency of current smokers was higher in the young group (67.6%) than in the older group (44.9%) (P < 0.001). Although the prevalence of hypertension was lower in the young group (66.7%) than in the older group (77.2%) (P = 0.017), that of untreated hypertension was greater in the young group (40.4%) than in the older group (27.2%) (P = 0.007). Furthermore, the prevalence of untreated dyslipidemia was greater in the young group (45.0%) than in the older group (26.6%) (P < 0.001). In conclusion, the young AMI patients had more modifiable risk factors such as obesity, smoking, untreated hypertension, and untreated dyslipidemia than the older patients. There is an unmet medical need for the prevention of AMI in the young generation.

Active Participation in Outpatient Cardiac Rehabilitation Is Associated With Better Prognosis After Coronary Artery Bypass Graft Surgery　- J-REHAB CABG Study.

BACKGROUND: There is little evidence regarding the effect of outpatient cardiac rehabilitation (CR) on exercise capacity or the long-term prognosis in patients after coronary artery bypass graft surgery (CABG). This study aimed to determine whether participation in outpatient CR improves exercise capacity and long-term prognosis in post-CABG Japanese patients in a multicenter cohort.Methods and Results:We enrolled 346 post-CABG patients who underwent cardiopulmonary exercise testing during early (2-3 weeks) and late (3-6 months) time points after surgery. They formed the Active (n=240) and Non-Active (n=106) CR participation groups and were followed for 3.5 years. Primary endpoint was a major adverse cardiac event (MACE): all-cause death or rehospitalization for acute myocardial infarction/unstable angina/worsening heart failure. Peak oxygen uptake at 3-5 months from baseline was significantly more increased in Active than in Non-Active patients (+26±24% vs. +19±20%, respectively; P<0.05), and the MACE rate was significantly lower in Active than Non-Active patients (3.4% vs. 10.5%, respectively; P=0.02). Multivariate Cox proportional hazard analysis showed that participation in outpatient CR was a significant prognostic determinant of MACE (P=0.03). CONCLUSIONS: This unique study showed that a multicenter cohort of patients who underwent CABG and actively participated in outpatient CR exhibited greater improvement in exercise capacity and better survival without cardiovascular events than their counterparts who did not participate.

Association of less-contrast media with clinical factors in elective percutaneous coronary intervention.

Since the amount of contrast media during percutaneous coronary intervention (PCI) is closely related to the exacerbation of renal function, it should be important to reduce the dose of contrast media during PCI. The purpose of this retrospective study was to evaluate the association of less-contrast media with clinical factors in elective PCI. A total of 709 patients were divided into the less-contrast media group (n = 142) and the conventional-contrast media group (n = 567) according to the quintile of total contrast volume. Univariate and multivariate logistic regression analyses were performed to find associations between the clinical variables and the less-contrast media group. The intravascular ultrasound (IVUS) use rate in the study population was considerably high (94.9%). In multivariable logistic regression analysis, an eGFR < 30 mL/min/1.73 m2 without hemodialysis was significantly associated with the less-contrast media group [odds ratio (OR) 43.73, 95% confidence interval (CI) 14.05-136.09, P < 0.001]. Left main-left anterior descending artery lesion (OR 0.28, 95% CI 0.17-0.48, P < 0.001), bifurcation lesion (OR 0.39, 95% CI 0.16-0.92, P = 0.03), chronic total occlusion (OR 0.22, 95% CI 0.06-0.90, P = 0.03) were inversely associated with the less-contrast media group. In conclusion, complex lesion characteristics were inversely associated with the less-contrast media in elective PCI. Since operators could access patients' renal function before elective procedure, an eGFR < 30 mL/min/1.73 m2 was most significantly associated with the less-contrast media. Our results suggest the possibility that the amount of contrast media is controllable in current PCI under IVUS-guidance.

Comparison of In-Hospital Clinical Outcomes of Acute Myocardial Infarction Between Nonagenarians and Octogenarians.

Acute myocardial infarction (AMI) in the very elderly is associated with high morbidity and mortality. Although there are earlier studies regarding AMI in octogenarians, clinical evidences of AMI in nonagenarians are sparse. The aim of the present study was to compare in-hospital outcomes of AMI between octogenarians and nonagenarians. We included consecutive 415 very elderly (≥ 80 years) with AMI and divided them into the nonagenarian group (n = 38) and the octogenarian group (n = 377). Clinical characteristics and in-hospital outcomes were compared between the two groups. Furthermore, we used propensity score matching to find the matched octogenarian group (n = 38). Percutaneous coronary interventions (PCI) to the culprit of AMI were similarly performed between the nonagenarian (86.8%) and octogenarian (87.0%) groups. The incidence of in-hospital death in the nonagenarian group (10.5%) was similar to that in the octogenarian group (12.5%) (P = 0.487). After using the propensity score matching, the incidence of in-hospital death was less in the nonagenarian group (10.5%) than in the matched octogenarian group (18.4%) without reaching statistical significance (P = 0.328). The length of hospitalization was significantly shorter in the nonagenarian group [7.0 (4.0-9.0)] than in the matched octogenarian group [10.0 (6.5-15.0)] (P = 0.01). In conclusion, the in-hospital mortality of nonagenarians with AMI was comparable to that of octogenarians with AMI. In-hospital outcomes in nonagenarians with AMI may be acceptable as long as acute medical management including PCI to the culprit of AMI is performed.

Mid-term Clinical Outcomes of Immediate Protamine Use Following Elective Percutaneous Coronary Interventions.

Bleeding complication has been considered as a serious problem in current percutaneous coronary interventions (PCI). Fortunately, several groups have already reported the effectiveness of protamine use just after PCI to immediately remove any arterial sheath. However, there is a concern that protamine reversal may increase non-occlusive thrombus and, in turn, lead to mid-term cardiovascular events such as target vessel revascularization (TVR) or stent thrombosis. Thus, the purpose of this study was to evaluate whether protamine use following elective PCI was associated with mid-term clinical outcomes. In total, 472 patients were included in this study; subsequently, they were divided into protamine group (n = 142) and non-protamine group (n = 330). The primary endpoint was the composite of ischemia-driven TVR and stent thrombosis. The median follow-up period was determined to be at 562 days. In total, 32 primary endpoints were observed during the study period, and the incidence of primary endpoints tended to be greater in the protamine group than in the non-protamine group (P = 0.056). However, the lesion length, the degree of calcification, and the prevalence of hemodialysis were significantly determined greater in the protamine group than in the non-protamine group. In the multivariate Cox proportional hazards model, the use of protamine (versus non-protamine: hazard ratio 0.542 and 95% confidence interval 0.217-1.355, P = 0.191) was deemed not to be associated with the primary endpoint after controlling legion length, calcification, and hemodialysis. In conclusion, immediate protamine use following elective PCI did not increase mid-term ischemia-driven TVR or stent thrombosis. However, immediate protamine use after PCI should be discussed further for the safety of the patient.

Determinants of In-Hospital Death Among the Very Elderly with Acute Myocardial Infarction.

Since the number of elderly patients suffering from acute myocardial infarction (AMI) has been increasing in developed countries, primary percutaneous coronary intervention (PCI) for the very elderly aged ≥80 years old is already common. The study aimed to examine the determinants of in-hospital death among the very elderly with AMI in current PCI era. We included 412 consecutive AMI patients aged ≥ 80 years old who received PCI to the culprit lesion; however, 42 patients (10.2%) died during the index hospitalization. Thus, univariate and multivariate logistic regression analyses were performed to identify the determinants of in-hospital death. Of note, the modified KATZ index, which is a seven-point scale ranging from 0 to 6 (0 point indicating no dependence and six points indicating full dependence), was calculated to evaluate pre-admission activity of daily living (ADL). In multivariate analysis, cardiac arrest (OR 4.642, 95% CI 1.177-18.305, P = 0.028), Killip class IV (versus Killip class I: OR 5.732, 95% CI 1.076-16.630, P = 0.001), modified KATZ index (OR 1.212, 95% CI 1.001-1.469, P = 0.049), hemoglobin levels (OR 0.803, 95% CI 0.656-0.983, P = 0.033), use of temporary pacemaker (OR 2.603, 95% CI 1.010-6.709, P = 0.048), final Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 (versus TIMI ≤ 2: OR 0.240, 95% CI 0.093-0.618, P = 0.003), and mechanical circulatory support (OR 4.264, 95% CI 1.818-10.005, P = 0.001) were found to be significantly associated with in-hospital death. In conclusion, in-hospital outcomes of the very elderly with AMI were still poor in the current PCI era. Poor pre-admission ADL as well as cardiogenic shock and anemia were determined to be strongly associated with in-hospital death.

Determinants of Periprocedural Myocardial Infarction in Current Elective Percutaneous Coronary Interventions.

Periprocedural myocardial infarction (PMI) is closely associated with long-term cardiovascular events. The factors associated with PMI are not fully understood. The purpose of this study was to investigate the determinants of PMI in contemporary elective percutaneous coronary intervention (PCI). Overall, 731 elective PCI was divided into the PMI (n = 27) and non-PMI (n = 704) groups. Univariate and multivariate logistic regression analysis was used to find factors associated with PMI. In the univariate analysis, PMI was associated with complex lesion characteristics, such as the lesion length, lesion angle, calcification, and Medina classification. In the multivariate logistic regression analysis, the lesion length (per 10-mm increase: odds ratio (OR), 1.477; 95% confidence interval (CI), 1.161‒1.879; P = 0.002), lesion angle ≥ 45° (versus lesion angle < 45°: OR, 4.244; 95% CI, 1.187‒15.171; P = 0.026), and Medina classification (0,1,1) / (1,1,1) (versus other lesions: OR, 14.843; 95% CI, 6.235‒35.334; P < 0.001) were significantly associated with PMI. Of the 24 lesions with lesion angle ≥ 45° in the PMI group, 14 had final TIMI flow grade ≤ 2 in side branches and 9 had transient slow flow in main branches/transient ST elevation during PCI. Of the 87 lesions with Medina classification (1,1,1) / (0,1,1), 19 had final TIMI grade ≤ 2 in side branches. In conclusion, the lesion length, lesion angle ≥ 45°, and Medina classification (0,1,1) / (1,1,1) were significantly associated with PMI in contemporary elective PCI. Preventing flow limitation in both side branches and main vessels in elective PCI for the diffuse long, angulated, or true bifurcation lesions is important.

Clinical Factors Associated with In-Hospital Mortality in Patients with Acute Myocardial Infarction Who Required Intra-Aortic Balloon Pumping.

Recent guidelines do not recommend the routine use of intra-aortic balloon pumping (IABP) for patients with cardiogenic shock. However, IABP support is still selected for acute myocardial infarction (AMI) in clinical practice because an Impella device did not show superiority over IABP and the mortality of AMI with cardiogenic shock is still high. This study aimed to find factors associated with in-hospital mortality in patients with AMI who required IABP support. Overall, 104 patients with AMI who required IABP support were included as the study population. Of 104 patients, in-hospital death was observed in 19 (18.3%). Multivariate stepwise logistic regression analysis was performed to investigate the determinants of in-hospital death. Shock, resuscitation, estimated glomerular filtration rate (eGFR), pre-systolic blood pressure of IABP insertion, multi-vessel disease, fluoroscopy time, initial lactic acid dehydrogenase levels, and timing of IABP support were included as independent variables. Shock (OR 25.27, 95% CI 3.26-196.11, P = 0.002) was significantly associated with in-hospital death after controlling other covariates, whereas eGFR (every 10 mL/minute/1.73 m2 increase: OR 0.65, 95% CI 0.51-0.82, P < 0.001) and pre-percutaneous coronary intervention (pre-PCI) insertion of IABP (versus on-PCI insertion of IABP: OR 0.06, 95% CI 0.008-0.485, P = 0.008) were inversely associated with in-hospital death. In conclusion, shock was significantly associated with in-hospital death, whereas eGFR and pre-PCI insertion of IABP were inversely associated with in-hospital death in patients with AMI who received IABP support. Pre-PCI insertion of an IABP catheter might be associated with better survival in AMI patients who potentially require IABP support.