Optimizing Percutaneous Mitral Valvuloplasty for Rheumatic Mitral Stenosis　- Clinical Significance of Changes in Mitral Valve Area.

BACKGROUND: Percutaneous mitral valvuloplasty (PMV) is a standard treatment for severe rheumatic mitral stenosis (RMS). However, the prognostic significance of the change in mitral valve area (∆MVA) during PMV is not fully understood.Methods and Results: This study analyzed data from the Multicenter mitrAl STEnosis with Rheumatic etiology (MASTER) registry, which included 3,140 patients with severe RMS. We focused on patients with severe RMS undergoing their first PMV. Changes in echocardiographic parameters, including MVA quantified before and after PMV, and composite outcomes, including mitral valve reintervention, heart failure admission, stroke, and all-cause death, were evaluated. An optimal result was defined as a postprocedural MVA ≥1.5 cm2without mitral regurgitation greater than Grade II. Of the 308 patients included in the study, those with optimal results and ∆MVA >0.5 cm² had a better prognosis (log-rank P<0.001). Patients who achieved optimal results but with ∆MVA ≤0.5 cm² had a greater risk of composite outcomes than those with optimal outcomes and ∆MVA >0.5 cm² (nested Cox regression analysis, hazard ratio 2.27; 95% confidence interval 1.09-4.73; P=0.028). CONCLUSIONS: Achieving an increase in ∆MVA of >0.5 cm2was found to be correlated with improved outcomes. This suggests that, in addition to achieving traditional optimal results, targeting an increase in ∆MVA of >0.5 cm2could be a beneficial objective in PMV treatment for RMS.

Shifts in Clinical Characteristics, Treatment, and Outcome for Rheumatic Mitral Stenosis: Insights From a 20-Year Multicentre Registry Study in Korea.

BACKGROUND: The rapid economic development of South Korea provides a unique model to study changes in the clinical characteristics, treatment approaches, and clinical outcomes of patients with rheumatic mitral stenosis (MS) relative to socioeconomic growth. METHODS: From the Multicenter mitrAl STEnosis with Rheumatic etiology (MASTER) registry, 2,337 patients diagnosed with moderate or severe rheumatic MS between January 2001 and December 2020 were analyzed. Patients were grouped into consecutive 5-year intervals based on their year of diagnosis. Clinical characteristics, echocardiographic data, and clinical outcomes were assessed. RESULTS: Over 20 years, the severity of mitral stenosis increased from 79.1% to 90.2%; similarly, the average age at diagnosis increased from 54.3 to 63.0 years (all P < 0.001). Comorbidities such as hypertension and atrial fibrillation increased (6.3% to 29.5% and 41.4% to 46.9%, respectively; all P for trend < 0.05). The rate of mitral intervention within five years after diagnosis increased from 31.2% to 47.4% (P for trend < 0.001). However, clinical outcomes of rheumatic mitral stenosis deteriorated over time in the composite outcomes (log-rank test, P < 0.001). Conversely, the incidence of stroke remained stable (60.6-73.7%; P < 0.001), which might be attributed to the increased use of anticoagulation therapy. CONCLUSION: This study observed an increase in patient age, comorbidities, and valve disease severity as the country transitioned from a developing to developed status. Despite a rise in mitral valve interventions, clinical outcomes deteriorated over 20 years, highlighting the need for modified treatment approaches to improve patient outcomes.

Alcohol-induced increase in BMP levels promotes fatty liver disease in male prediabetic stage Otsuka Long-Evans Tokushima Fatty rats.

Alcohol consumption exacerbates liver abnormalities in animal models, but whether it increases the severity of liver disease in early diabetic or prediabetic rats is unclear. To investigate the molecular mechanisms underlying alcohol-induced liver steatosis or hepatitis, we used a prediabetic animal model. Otsuka Long-Evans Tokushima Fatty (OLETF) and Long-Evans Tokushima Fatty (LETO) rats were pair-fed with an ethanol-containing liquid diet for 6 weeks. Compared with controls, OLETF and LETO rats displayed more pronounced liver steatosis and higher plasma levels of serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SPGT), indicating liver injury. Ethanol-fed LETO (Pd-L-E) rats showed mild liver steatosis and no inflammation compared with ethanol-fed OLETF (Pd-O-E) rats. Although precursor and active SREBP-1 levels in the liver of ethanol-fed OLETF rats significantly increased compared with control diet-fed OLETF rats (Pd-O-C), those of Pd-L-E rats did not. Bone morphogenetic protein (BMP) and TGF-ß1 balance in Pd-O-E rats was significantly altered because BMP signaling was upregulated by inducing BMP2, BMP4, BMP7, BMP9, Smad1, and Smad4, whereas TGF-ß1, Smad3, and Erk were downregulated. Activation of TGF-ß/Smad signaling inhibited BMP2 and BMP9 expression and increased epithelial-mesenchymal transition (EMT) marker levels (Hepcidin, Snail, and Twist) in the liver of LETO rats. Livers of ethanol-fed OLETF rats showed increased levels of vimentin, FSP-1, α-SMA, MMP1, MMP13, and collagen III compared with rats of other groups, whereas EMT marker levels did not change. Thus, BMP exerted anti- and/or pro-fibrotic effects in ethanol-fed rats. Therefore, BMP and TGF-ß, two key members of the TGF-ß superfamily, play important but diverse roles in liver steatosis in young LETO and OLETF rats.

Clinical Implication of 'Obesity Paradox' in Elderly Patients With Acute Myocardial Infarction.

BACKGROUND: The clinical impact of body mass index (BMI), especially in the elderly with acute myocardial infarction (AMI), has not been sufficiently evaluated. The purpose of this study was to elucidate the clinical impact of BMI in very old patients (≥80 years) with AMI. METHODS: The study analysed 2,489 AMI patients aged ≥80 years from the Korea Acute Myocardial Infarction Registry and the Korea Working Group on Myocardial Infarction (KAMIR/KorMI) registries between November 2005 and March 2012. The study population was categorised into four groups based on their BMI: underweight (n=301), normal weight (n=1,150), overweight (n=890), and obese (n=148). The primary endpoint was major adverse cardiovascular event (MACE), a composite of cardiac death, myocardial infarction, target lesion revascularisation, and target vessel revascularisation. RESULTS: Baseline characteristics among the four groups were similar, except for hypertension (45.1 vs 58.4 vs 66.2 vs 69.9%, respectively; p<0.001) and diabetes (16.6 vs 23.6 vs 30.7 vs 35.1%, respectively; p<0.001). Coronary care unit length of stay was significantly different among the four groups during hospitalisation (5.3±5.9 vs 4.8±6.8 vs 4.2±4.0 vs 3.5±2.1 days; p=0.007). MACE (16.9 vs 14.9 vs 13.7 vs 8.8%; p=0.115) and cardiac death (10.3 vs 8.4 vs 7.9 vs 4.1%; p=0.043) less frequently occurred in the obese group than in other groups during the 1-year follow-up. A multivariate regression model showed obese status (BMI ≥27.5 kg/m2) as an independent predictor of reduced MACE (hazard ratio [HR], 0.20; 95% confidence interval [CI], 0.06-0.69; p=0.010) along with reduced left ventricular ejection fraction (≤40%) as a predictor of increased MACE (HR,1.87; 95% CI, 1.31-2.68; p=0.001). CONCLUSION: Body mass index in elderly patients with acute myocardial infarction was significantly associated with coronary care unit stay and clinical cardiovascular outcomes.

Long-term insulin treatment leads to a change in myosin heavy chain fiber distribution in OLETF rat skeletal muscle.

The objective of this study was to investigate molecular and physiological changes in response to long-term insulin glargine treatment in the skeletal muscle of OLETF rats. Male Otsuka Long-Evans Tokushima Fatty (OLETF) and Long-Evans Tokushima Otsuka (LETO) rats aged 24 weeks were randomly allocated to either treatment with insulin for 24 weeks or no treatment, resulting in three groups. Insulin glargine treatment in OLETF rats (OLETF-G) for 24 weeks resulted in changes in blood glucose levels in intraperitoneal glucose tolerance tests compared with age-matched, untreated OLETF rats (OLETF-C), and the area under the curve was significantly decreased for OLETF-G rats compared with OLETF-C rats (P < 0.05). The protein levels of MHC isoforms were altered in gastrocnemius muscle of OLETF rats, and the proportions of myosin heavy chain type I and II fibers were lower and higher, respectively, in OLETF-G compared with OLETF-C rats. Activation of myokines (IL-6, IL-15, FNDC5, and myostatin) in gastrocnemius muscle was significantly inhibited in OLETF-G compared with OLETF-C rats ( P < 0.05). MyoD and myogenin levels were decreased, while IGF-I and GLUT4 levels were increased, in the skeletal muscle of OLETF-G rats ( P < 0.05). Insulin glargine treatment significantly increased the phosphorylation levels of AMPK, SIRT1, and PGC-1α. Together, our results suggested that changes in the distribution of fiber types by insulin glargine could result in downregulation of myokines and muscle regulatory proteins. The effects were likely associated with activation of the AMPK/SIRT1/PGC-1α signaling pathway. Changes in these proteins may at least partly explain the effect of insulin in skeletal muscle of diabetes mellitus.

Normative Values of Short-Term Heart Rate Variability Parameters in Koreans and Their Clinical Value for the Prediction of Mortality.

BACKGROUND: Heart rate variability (HRV) analysis is an important clinical tool for characterising cardiac autonomic status. We sought to determine the normative values and characteristics of the HRV parameters derived from a short-term study in Koreans and to determine their clinical role in predicting mortality. METHODS: A total of 1828 consecutive patients (range 20-84 years, men 64.8%) with no serious comorbid conditions were recruited. The RR intervals from 10-minute electrocardiograms were used for computation of the following HRV parameters: conventional time- and frequency-domain measures and nonlinear measures. RESULTS: A greater age-dependence of most conventional parameters, including the low frequency (LF) and high frequency (HF) powers, was observed than that of the Shannon entropy (ShanEn), approximate entropy (ApEn), and sample entropy. Fifty-four patients (14 cardiac deaths) died during a 10-year follow-up period. The LF/HF ratio (odds ratio [OR], 0.876; p=0.025), ShanEn (OR, 0.372; p=0.028), and ApEn (OR, 0.093; p=0.030) were found to be predictors of all-cause mortality in the multivariate regression analysis. Age was also a powerful risk factor for all-cause mortality (OR, 1.141; p<0.001). CONCLUSIONS: We presented the normative values and characterised the short-term HRV parameters in Koreans. Among the short-term nonlinear parameters, the ShanEn and ApEn were adjunctive parameters for predicting the all-cause mortality in the general population.

A comparison of echocardiographic variables of right ventricular function with exercise capacity after bosentan treatment in patients with pulmonary arterial hypertension: Results from a multicenter, prospective, cohort study.

PURPOSE: Bosentan reduces pulmonary arterial pressure and improves exercise capacity in patients with pulmonary arterial hypertension (PAH). However, there are limited data regarding the extent to which the changes in echocardiographic variables reflect improvements in exercise capacity. We aimed to assess the improvement of echocardiographic variables and exercise capacity after 6 months of bosentan treatment for PAH. METHODS: We performed a prospective study from June 2012 to June 2015 in seven participating medical centers. Echocardiography, including tissue Doppler imaging (TDI) and the 6-minute walk test distance (6MWD), was performed at baseline and after 6 months of bosentan treatment. RESULTS: We analyzed 19 patients with PAH: seven with congenital shunt, six with collagen vascular disease, and six with idiopathic PAH. After bosentan treatment, mean 6MWD increased by 50 meters. Right ventricle (RV) systolic pressure, tricuspid annular plane systolic excursion, myocardial performance index (MPI) derived from TDI (MPI-TDI) of RV and left ventricle (LV), RV fractional area change, and RV ejection fraction were significantly improved. In particular, the magnitude of RV and LV MPI-TDI showed good correlation with changes in the 6MWD. CONCLUSIONS: The magnitude of RV and LV MPI-TDI was strongly associated with improvements in exercise capacity. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:28-34, 2017.

Fabry disease in patients with hypertrophic cardiomyopathy: a practical approach to diagnosis.

This study aimed to develop a new set of screening criteria that is easily applicable and highly sensitive for the detection of patients at high risk of Fabry disease (FD) among hypertrophic cardiomyopathy (HCM) patients. We prospectively studied 273 consecutive unrelated patients who were referred to HCM clinic for unknown left ventricular hypertrophy. Among the 273 patients, we selected 65 high-risk patients who fulfilled at least one of our newly proposed screening criteria. All 273 patients were assayed for plasma α-galactosidase A (α-GAL A) activity. The new screening criteria were: (1) atypical HCM, (2) history or presence of documented arrhythmia, (3) short PR interval defined as <120 ms on electrocardiogram, and (4) symptoms of autonomic dysfunction. From this screening study, three unrelated patients (4.6%; 2 females and 1 male) were newly diagnosed with FD using α-GAL A activity and mutation analysis of the GLA gene. Using the screening method based on the newly proposed criteria, the prevalence of FD in our HCM population was 4.6% if at least one criterion was met and 18.8% if ⩾3 criteria were met. Therefore, our proposed criteria are easily applicable and highly sensitive for classifying patients at high risk of FD from HCM patients.

Analytical Performance Evaluation of Infopia Element™ Auto-coding Blood Glucose Monitoring System for Self-Monitoring of Blood Glucose.

BACKGROUND: Element™ Auto-coding Blood Glucose Monitoring System (BGMS; Infopia Co., Ltd., Anyang-si, Korea) was developed for self-monitoring of blood glucose (SMBG). METHODS: Precision, linearity, and interference were tested. Eighty-four capillary blood samples measured by Element™ BGMS were compared with central laboratory method (CLM) results in venous serum. Accuracy was evaluated using ISO 15197:2013 criteria. RESULTS: Coefficients of variation (CVs; mean) were 2.4% (44.2 mg/dl), 3.7% (100.6 mg/dl), and 2.1% (259.8 mg/dl). Linearity was shown at concentrations 39.25-456.25 mg/l (y = 0.989 + 0.984x, SE = 17.63). Up to 15 mg/dl of galactose, ascorbic acid, and acetaminophen, interference > 10.4% was not observed. Element™ BGMS glucose was higher than CLM levels by 3.2 mg/dl (at 200 mg/dl) to 8.2 mg/dl (at 100 mg/dl). The minimum specification for bias (3.3%) was met at 140 and 200 mg/l glucose. In the Clarke and consensus error grids, 100% of specimens were within zone A and B. For Element™ BGMS values, 92.9% (78/84) to 94.0% (79/84) were within a 15 mg/dl (< 100 mg/dl) or 15% (> 100 mg/dl) of the average CLM value. CONCLUSION: Element™ BGMS was considered an appropriate SMBG for home use; however, the positive bias at low-to-mid glucose levels requires further improvement.

High glucose and palmitate increases bone morphogenic protein 4 expression in human endothelial cells.

Here, we investigated whether hyperglycemia and/or free fatty acids (palmitate, PAL) aff ect the expression level of bone morphogenic protein 4 (BMP4), a proatherogenic marker, in endothelial cells and the potential role of BMP4 in diabetic vascular complications. To measure BMP4 expression, human umbilical vein endothelial cells (HUVECs) were exposed to high glucose concentrations and/or PAL for 24 or 72 h, and the effects of these treatments on the expression levels of adhesion molecules and reactive oxygen species (ROS) were examined. BMP4 loss-of-function status was achieved via transfection of a BMP4-specific siRNA. High glucose levels increased BMP4 expression in HUVECs in a dose-dependent manner. PAL potentiated such expression. The levels of adhesion molecules and ROS production increased upon treatment with high glucose and/or PAL, but this eff ect was negated when BMP4 was knocked down via siRNA. Signaling of BMP4, a proinflammatory and pro-atherogenic cytokine marker, was increased by hyperglycemia and PAL. BMP4 induced the expression of infl ammatory adhesion molecules and ROS production. Our work suggests that BMP4 plays a role in atherogenesis induced by high glucose levels and/or PAL.

Increased variability of the coupling interval of premature ventricular contractions as a predictor of cardiac mortality in patients with left ventricular dysfunction.

BACKGROUND: The characteristics and prognostic value of the variability of premature ventricular contraction (PVC) coupling intervals (CIs) for cardiac mortality are not yet decisive. METHODS AND RESULTS: In 133 consecutive patients (58±14 years old, 53 women) who had left ventricular dysfunction (LVD: ejection fraction <50%) and frequent PVCs (≥10/h) who underwent 24-h ambulatory electrocardiography (AECG) recording and (123)I-metaiodobenzylguanidine myocardial single-photon emission computed tomography simultaneously, the heart rate turbulence onset, slope, and T-wave alternans were analyzed from the 24-h AECG. The CI of the PVCs (MEANNV), standard deviation of the CI of the PVCs (SDNV) as an index of the variability of the PVC CI, and their ratio to the preceding N-N intervals (SDNV/SDNN) were calculated from constructed Poincaré plots using the annotated 24-h AECG QRS data. The primary endpoint was cardiac mortality. The mean follow-up period was 63 months. Among 133 patients, 114 survived (group 1) and 19 (14%, group 2) died during the follow-up. The MEANNVand SDNVwere higher in group 2 (539±104 vs. 599±114 ms, P=0.021; 64±34 vs. 83±37 ms, P=0.022, respectively). The SDNV, PVC count, and delayed heart/mediastinum ratio remained as significant predictors of cardiac mortality in the binary logistic regression analysis. CONCLUSIONS: These results suggest that the SDNVcould be another adjunctive parameter for predicting cardiac mortality in LVD.

A prospective, randomized, multicenter trial comparing the efficacy and safety of the concurrent use of long-acting insulin with mitiglinide or voglibose in patients with type 2 diabetes.

This trial was conducted to compare the efficacy and safety of combination therapy with basal insulin glargine plus mitiglinide to that of basal insulin glargine plus voglibosein patients with type 2 diabetes. This was a 20-week, randomized, multicenter non-inferiority trial. Patients with HbA1c levels over 7.0% were randomly assigned to receive either mitiglinide (10 mg tid) or voglibose (0.2 mg tid) concurrent with insulin glargine for 16 weeks after a 4-week of basal insulin glargine monotherapy. The intention-to-treat population included 156 patients; 79 were placed in the mitiglinide group, and 77 were placed in the voglibose group. At 20 weeks, there was no significant difference between the mitiglinide group and the voglibose group in terms of the mean HbA1c level or the mean decrease of the HbAlc level from baseline (-0.9% [-7.5 mmol/mol] and -0.7%, [-5.3 mmol/mol] respectively). The mean fasting plasma glucose level and data of self-monitoring blood glucosewere significantly decreased from baseline to week 20 in both groups, but there was no significant difference between the two groups. The changes in the basal insulin requirements of each group were not significant. The prevalence of adverse events and the risk of hypoglycemia were similar for both groups. Combination therapy with mitiglinide plus basal insulin glargine was non-inferior to voglibose plus basal insulin glargine in terms of the effect on overall glycemic control.

Reverse Takotsubo Cardiomyopathy following Inadvertent Intrathecal Injection during Percutaneous Epidural Neuroplasty.

Stress induced cardiomyopathy (SIC) is becoming increasingly described as an underdiagnosed complication during common medical procedures. Reverse Takotsubo cardiomyopathy (RTC) is a variant of SIC that involves the basal and mid-ventricular segments and spares the apical segments. The authors present a rare case of RTC, following an inadvertent intrathecal injection during percutaneous epidural neuroplasty. Although the precise mechanism involved remains unclear, the direct neurohumoral effects of the hyperbaric anaesthetics and adhesiolytics appear to have resulted in a catecholamine surge and myocardial stunning that precipitated the SIC.

Comprehensive three-dimensional analysis of right-sided aortic arch with multiple vascular anomalies.

BACKGROUND: Right-sided aortic arch is a rare congenital defect usually diagnosed incidentally in adults; it is often asymptomatic unless aneurismal disease develops. In half the cases, an aberrant left subclavian artery arises from a Kommerell's diverticulum; in these cases, congenital heart anomaly is very rarely present. CASE PRESENTATION: We report a case of incidentally-detected right-sided aortic arch with multiple vascular anomalies including left subclavian artery originating from a Kommerell's diverticulum, supra-sinus origin of coronary arteries and coronary arteriovenous fistula. CONCLUSION: Through comprehensive 3-dimensional reconstruction of the aortic arch and surrounding structures we defined anatomical relationships, which is useful for follow-up and treatment.

Treatment patterns and their outcomes of acute aortic intramural hematoma in real world: multicenter registry for aortic intramural hematoma.

BACKGROUND: Intramural hematoma of the aorta (IMH), a variant of classic aortic dissection, shows very dynamic process in the early phase. The aim of this study is to evaluate clinical outcomes of patients with acute aortic IMH from real world registry data. METHODS: We analyzed 165 consecutive patients with acute IMH from five medical centers in Korea. All patients were divided into two groups; type A (n = 61, 37.0%) and type B (n = 104, 63.0%) according to the Stanford classification. Clinical outcomes and morphological evolution by CT were analyzed for 2 years. RESULTS: Most of the patients (77.0% of type A and 99.0% of type B, P < 0.001) were treated medically during their initial hospitalization. There were no significant differences in in-hospital mortality (4.9% vs. 2.9%, P = 0.671) and 2-year mortality (13.1% vs. 11.5%, P = 0.765) between two groups. During the 2-year follow up period, progression to aortic dissection (18.0% vs. 6.7%, P = 0.037) and surgical treatment (29.5% vs. 2.9%, P < 0.001) were higher in type A. For the type A patients, there were no significant difference in in-hospital mortality (7.1% of surgery vs. 4.3% of medical, P = 0.428) and 2-year mortality (7.1% of surgery vs. 14.9% of medical, P = 0.450) in terms of initial treatment strategy. CONCLUSION: For real world practice in Korea, most of IMH patients were treated medically at presentation and showed favorable outcomes. Thus, even in type A acute IMH, early medical treatment with alternative surgical conversion for selected, complicated cases would be a favorable treatment option.

Clinical impact of Q-wave presence on electrocardiogram at presentation of patients with ST-segment elevation myocardial infarction undergoing primary coronary intervention.

This study evaluated the clinical impact of Q-wave presence on ECG at presentation of patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).From April 2005 to September 2009, 184 consecutive STEMI patients who underwent primary PCI within 12 hours of chest pain onset were retrospectively evaluated. Patients were grouped according to the presence (Q positive, n = 109) or absence (Q negative, n = 75) of Q waves on initial ECG at emergency room presentation. Major adverse cardiac events (MACE) and stent thrombosis (ST) were evaluated for 2 years. Risk factors for MACE and left ventricular (LV) remodeling by echocardiography were also evaluated.Baseline characteristics, including reperfusion time and infarct location, were similar between the groups. The MACE rate at 2 years was higher in the Q-positive group (32.1%) than in the Q-negative group (13.3%, P = 0.005). Independent risk factors for MACE were the presence of Q-wave (P = 0.008, Odds ratio 3.139) and no-reflow phenomenon (P = 0.016, Odds ratio, 2.819). LV remodeling was more frequent in the Q-positive group (47.9%) than in the Q-negative (24.5%, P = 0.009) group. Initial Q-wave presence (P = 0.048, Odds ratio 2.380) and anterior wall MI (P = 0.009, Odds ratio, 3.425) were independent risk factors for LV remodeling.The presence of Q waves in ECG of patients presenting with STEMI undergoing primary PCI provides an independent prognostic marker of clinical outcomes and left ventricular remodeling.

Acute Mitral Valve Regurgitation Caused by Left Ventricular Pacing Wire During Transcatheter Aortic Valve Replacement.

Transcatheter aortic valve replacement is quickly becoming the standard of care for patients with severe aortic stenosis thanks to its minimally invasive nature and favorable outcomes. Recently, left ventricular pacing has been proposed as a safer alternative to traditional right heart pacing, which could simplify the transcatheter aortic valve replacement procedure overall, although procedural complications may still occur. This report describes a rare case of left ventricular pacing wire-induced acute severe mitral valve regurgitation during transcatheter aortic valve replacement.

Impact of Guideline-Directed Management Strategies for Low-Density Lipoprotein Cholesterol Control in Patients Who Underwent Percutaneous Coronary Intervention.

There are little direct comparative evidences of strategies between ≥50% and the absolute target goal of low-density lipoprotein cholesterol (LDL-C) level <55 mg/100 ml for the patients who underwent percutaneous coronary intervention (PCI). This study aimed to investigate the clinical impact of different strategies between 2 groups of patients who underwent PCI. A total of 3,104 patients with previous PCI were retrospectively enrolled from 2014 to 2020 at Yeungnam University Medical Center. The study population was stratified into 2 groups based on whether the LDL-C level was <55 mg/100 ml at the 1-year mark or not. Furthermore, the 50% reduction rate of LDL-C was also categorized based on whether it had decreased by ≥50% from the initial LDL-C level at the 1-year mark. The primary end point was 3-year major adverse cardiovascular events (MACEs) which were defined as a composite of cardiovascular death, nonfatal myocardial infarction, target lesion revascularization, hospitalization for heart failure, or nonfatal stroke. There was no significant difference between the LDL <55 mg/100 ml group and the LDL ≥55 mg/100 ml group in the risk of MACEs (hazard ratio 1.06, 95% confidence interval 0.81 to 1.38, p = 0.690) after propensity score matching. However, the group that achieved ≥50% reduction of LDL-C from baseline LDL-C level showed a significant reduction in the occurrence of MACEs in the subgroup of LDL-C level ≥55 mg/100 ml (hazard ratio 0.41, 95% confidence interval 0.19 to 0.89, p = 0.025) compared with the group with <50% reduction of LDL-C. In all patients, the achievement rate of target LDL-C <55 mg/100 ml and more than 50% reduction from baseline was 17.2%. In conclusion, guideline-directed management strategy of ≥50% reduction of LDL-C from the baseline will be needed to reduce the incidence of MACEs in patients with LDL-C ≥55 mg/100 ml who underwent PCI. Additional efforts to increase the target goal achievement rate of LDL-C are warranted.

Cardiovascular outcomes between dapagliflozin versus empagliflozin in patients with diabetes mellitus.

BACKGROUND: Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been demonstrated to decrease cardiovascular adverse events. However, there is little real-world clinical evidence regarding a direct comparison between dapagliflozin and empagliflozin in patients with diabetes mellitus (DM). HYPOTHESIS: A difference in the cardiovascular efficancy of dapagliflozin versus empagliflozin in DM patients was anticipated, aiming to guide the optimal choice of SGLT2 inhibitors based on cardiovascular outcomes. METHODS: From 2014 to 2020, a total of 1549 patients with DM who were prescribed SGLT2 inhibitors such as dapagliflozin or empagliflozin were retrospectively enrolled. We categorized the study population into two groups: dapagliflozin (n = 981) and empagliflozin group (n = 568). The primary endpoint was major adverse cardiovascular events (MACE), defined as a composite of all-cause death, myocardial infarction (MI), stroke, or hospitalization for heart failure (HF) over a 3-year period. RESULTS: Propensity-score matching was performed (537 patients in each group). The mean age and hemoglobin A1c were 58.2 ± 13.0 years and 8.4 ± 1.7%, respectively. There was no significant difference between the dapagliflozin and empagliflozin groups in the risk of MACE (3.7% vs. 4.8%, hazard ratio [HR], 1.31; 95% confidence interval [CI], 0.73-2.35; p = 0.349). Furthermore, there were no differences between the two groups in secondary endpoints including all-cause death, MI, stroke, and hospitalization for HF. Prior MI and history of HF were independent predictors of MACE. CONCLUSIONS: Dapagliflozin and empagliflozin showed no significant difference of real-world clinical cardiovascular outcomes in patients with DM over a 3-year period. Further large randomized clinical trials will be warranted for better evaluation.