Ertugliflozin for Functional Mitral Regurgitation Associated With Heart Failure: EFFORT Trial.

BACKGROUND: The morbidity and mortality rates of patients with heart failure (HF) and functional mitral regurgitation (MR) remain substantial despite guideline-directed medical therapy for HF. We evaluated the efficacy of ertugliflozin for reduction of functional MR associated with HF with mild to moderately reduced ejection fraction. METHODS: The EFFORT trial (Ertugliflozin for Functional Mitral Regurgitation) was a multicenter, double-blind, randomized trial to examine the hypothesis that the sodium-glucose cotransporter 2 inhibitor ertugliflozin is effective for improving MR in patients with HF with New York Heart Association functional class II or III, 35%≤ejection fraction<50%, and effective regurgitant orifice area of chronic functional MR >0.1 cm2 on baseline echocardiography. We randomly assigned 128 patients to receive either ertugliflozin or placebo in addition to guideline-directed medical therapy for HF. The primary end point was change in effective regurgitant orifice area of functional MR from baseline to the 12-month follow-up. Secondary end points included changes in regurgitant volume, left ventricular (LV) volume indices, left atrial volume index, LV global longitudinal strain, and NT-proBNP (N-terminal pro-B-type natriuretic peptide). RESULTS: The treatment groups were generally well-balanced with regard to baseline characteristics: mean age, 66±11 years; 61% men; 13% diabetes; 51% atrial fibrillation; 43% use of angiotensin receptor-neprilysin inhibitor; ejection fraction, 42±8%; and effective regurgitant orifice area, 0.20±0.12 cm2. The decrease in effective regurgitant orifice area was significantly greater in the ertugliflozin group than in the placebo group (-0.05±0.06 versus 0.03±0.12 cm2; P<0.001). Compared with placebo, ertugliflozin significantly reduced regurgitant volume by 11.2 mL (95% CI, -16.1 to -6.3; P=0.009), left atrial volume index by 6.0 mL/m2 (95% CI, -12.16 to 0.15; P=0.005), and LV global longitudinal strain by 1.44% (95% CI, -2.42% to -0.46%; P=0.004). There were no significant between-group differences regarding changes in LV volume indices, ejection fraction, or NT-proBNP levels. Serious adverse events occurred in one patient (1.6%) in the ertugliflozin group and 6 (9.2%) in the placebo group (P=0.12). CONCLUSIONS: Among patients with functional MR associated with HF, ertugliflozin significantly improved LV global longitudinal strain and left atrial remodeling, and reduced functional MR. Sodium-glucose cotransporter 2 inhibitors may be considered for patients with functional MR. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04231331.

Effect of ertugliflozin on left ventricular function in type 2 diabetes and pre-heart failure: the Ertu-GLS randomized clinical trial.

BACKGROUND: The therapeutic effects of ertugliflozin, a sodium-glucose cotransporter 2 inhibitor, on cardiovascular outcome are not fully understood. This study aimed to evaluate the efficacy and safety of ertugliflozin on cardiac function in people with type 2 diabetes and pre-heart failure. METHODS: We conducted a 24-week randomized, double-blind, placebo-controlled trial involving individuals with type 2 diabetes inadequately controlled with antidiabetic medications. Participants with left ventricular hypertrophy, E/e' >15, or impaired left ventricular global longitudinal strain (LVGLS) were randomized 1:1 to receive either ertugliflozin (5 mg once daily) or a placebo. The primary outcome was the change in LVGLS. Secondary outcomes included changes in left ventricular mass index (LVMI) and left ventricular ejection fraction (LVEF). Prespecified exploratory outcomes, including angiotensin-converting enzyme 2 (ACE2) and angiotensin (1-7) levels, were also assessed. RESULTS: A total of 102 individuals (mean age, 63.9 ± 9.2 years; 38% women) were included. The ertugliflozin group showed a significant improvement in LVGLS (- 15.5 ± 3.1% to - 16.6 ± 2.8%, P = 0.004) compared to the placebo group (- 16.7 ± 2.7% to - 16.4 ± 2.6%, P = 0.509), with a significant between-group difference (P = 0.013). Improvements in LVMI and LVEF were also observed. Additionally, significant reductions in HbA1c, systolic blood pressure, whole-body and visceral fat, uric acid, proteinuria, N-terminal pro-B-type natriuretic peptide, and lipoprotein(a) were noted. ACE2 and angiotensin (1-7) levels significantly increased in the ertugliflozin group compared to the placebo group and correlated with changes in LVGLS [r = 0.456, P < 0.001 for ACE2; r = 0.541, P < 0.001 for angiotensin (1-7)]. Adverse events were similar between the two groups. CONCLUSIONS: This study demonstrated that ertugliflozin has beneficial effects on left ventricular function in individuals with type 2 diabetes and pre-heart failure, and it provided insights into potential underlying mechanisms. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03717194.

Mildly Reduced Renal Function Is Associated With Increased Heart Failure Admissions in Patients With Hypertrophic Cardiomyopathy.

BACKGROUND: The association between renal dysfunction and cardiovascular outcomes has yet to be determined in patients with hypertrophic cardiomyopathy (HCM). We aimed to investigate whether mildly reduced renal function is associated with the prognosis in patients with HCM. METHODS: Patients with HCM were enrolled at two tertiary HCM centers. Patients who were on dialysis, or had a previous history of heart failure (HF) or stroke were excluded. Patients were categorized into 3 groups by estimated glomerular filtration rate (eGFR): stage I (eGFR ≥ 90 mL/min/1.73 m², n = 538), stage II (eGFR 60-89 mL/min/1.73 m², n = 953), and stage III-V (eGFR < 60 mL/min/1.73 m², n = 265). Major adverse cardiovascular events (MACEs) were defined as a composite of cardiovascular death, hospitalization for HF (HHF), or stroke during median 4.0-year follow-up. Multivariable Cox regression model was used to adjust for covariates. RESULTS: Among 1,756 HCM patients (mean 61.0 ± 13.4 years; 68.1% men), patients with stage III-V renal function had a significantly higher risk of MACEs (adjusted hazard ratio [aHR], 2.71; 95% confidence interval [CI], 1.39-5.27; P = 0.003), which was largely driven by increased incidence of cardiovascular death and HHF compared to those with stage I renal function. Even in patients with stage II renal function, the risk of MACE (vs. stage I: aHR, 2.21' 95% CI, 1.23-3.96; P = 0.008) and HHF (vs. stage I: aHR, 2.62; 95% CI, 1.23-5.58; P = 0.012) was significantly increased. CONCLUSION: This real-world observation showed that even mildly reduced renal function (i.e., eGFR 60-89 mL/min/1.73 m²) in patients with HCM was associated with an increased risk of MACEs, especially for HHF.

Comparison of the effects of gemigliptin versus glimepiride on cardiac function in patients with type 2 diabetes uncontrolled with metformin: The gemi-heart study.

AIM: To investigate the effects of gemigliptin on cardiac function and compare the effects of gemigliptin and glimepiride in patients with type 2 diabetes (T2D). MATERIALS AND METHODS: Sixty T2D patients being treated with metformin were assigned to a gemigliptin group (50 mg daily) or a glimepiride group (2 mg daily) for 24 weeks. The preadjudicated extension period was up to 52 weeks. Glucose metabolism variables and cardiac biomarkers were measured. Echocardiography was used to evaluate cardiac functions. RESULTS: The HbA1c levels decreased significantly from 8.1% ± 0.6% to 6.8% ± 0.6% in the gemigliptin group and from 8.1% ± 0.6% to 7.0% ± 0.7% in the glimepiride group, without a between-group difference. Gemigliptin reduced insulin resistance, high sensitivity C-reactive protein and low-density lipoprotein cholesterol levels, and blood pressure, and increased adiponectin level compared with glimepiride therapy. Gemigliptin induced favourable changes in body composition. Left ventricular end-diastolic volume decreased in the gemigliptin group but increased in the glimepiride group, with a borderline between-group difference. Cardiac biomarkers did not change significantly in either group. At 52 weeks, the HbA1c levels in both groups increased slightly; 7.3% ± 0.8% in the gemigliptin group versus 7.7% ± 1.3% in the glimepiride group, without a between-group difference. CONCLUSIONS: Gemigliptin had a comparable glucose-lowering efficacy without deleterious effects on cardiac functions or on biomarkers reflective of myocardial injury or heart failure during the 24-week observation period. However, larger, longer-term studies are needed to confirm these findings.

Preventive effect of Helicobacter pylori eradication on the coronary heart diseases depending on age and sex with a median follow-up of 51 months.

BACKGROUND: The association between Helicobacter pylori (HP) infection and coronary heart disease (CHD) is controversial. This study aimed to investigate the effect of H. pylori eradication on CHD, especially in terms of age and sex. MATERIALS AND METHODS: From May 2003 to March 2022, 4765 subjects with H. pylori infection and without CHD (median follow-up: 51 months) were prospectively enrolled. The participants were categorized into two groups: H. pylori eradication and H. pylori non-eradication. After propensity-score matching (PSM), the effect of H. pylori eradication on CHD was analyzed using Cox proportional hazards. RESULTS: There were no significant differences in age, sex, alcohol consumption, smoking habits, history of diabetes, hypertension, and dyslipidemia, and aspirin intake between the eradication and non-eradication groups (3783 vs. 982) before and after PSM. Multivariate analysis after PSM showed that H. pylori eradication (HR: 0.489, CI: 0.314-0.761, p = .002), age (HR: 1.027, CI: 1.007-1.047, p = .007), hypertension (HR: 2.133, CI: 1.337-3.404, p = 001), dyslipidemia (HR: 1.758, CI: 1.086-2.848, p = .022), and aspirin intake (HR: 2.508, CI: 1.566-4.017, p < .001) were associated with CHD development. H. pylori eradication prevented CHD in males ≤65 years (HR: 0.133, CI: 0.039-0.455, p = .001), but not in those aged >65 years (p = .078) (p for interaction = .022). In contrast, females aged >65 years (HR: 0.260, CI: 0.110-0.615, p = .002) were protected by H. pylori eradication and not those ≤65 years (p = .485) (p for interaction = .003). This preventive effect increased more after PSM, particularly in males ≤65 years and females >65 years. CONCLUSIONS: H. pylori eradication prevented CHD and this effect was different depending on age and sex.

Impact of glycemic control on the progression of aortic stenosis: a single-center cohort study using a common data model.

BACKGROUND: Diabetes mellitus (DM) is a well-established risk factor for the progression of degenerative aortic stenosis (AS). However, no study has investigated the impact of glycemic control on the rate of AS progression. We aimed to assess the association between the degree of glycemic control and the AS progression, using an electronic health record-based common data model (CDM). METHODS: We identified patients with mild AS (aortic valve [AV] maximal velocity [Vpeak] 2.0-3.0 m/sec) or moderate AS (Vpeak 3.0-4.0 m/sec) at baseline, and follow-up echocardiography performed at an interval of ≥ 6 months, using the CDM of a tertiary hospital database. Patients were divided into 3 groups: no DM (n = 1,027), well-controlled DM (mean glycated hemoglobin [HbA1c] < 7.0% during the study period; n = 193), and poorly controlled DM (mean HbA1c ≥ 7.0% during the study period; n = 144). The primary outcome was the AS progression rate, calculated as the annualized change in the Vpeak (△Vpeak/year). RESULTS: Among the total study population (n = 1,364), the median age was 74 (IQR 65-80) years, 47% were male, the median HbA1c was 6.1% (IQR 5.6-6.9), and the median Vpeak was 2.5 m/sec (IQR 2.2-2.9). During follow-up (median 18.4 months), 16.1% of the 1,031 patients with mild AS at baseline progressed to moderate AS, and 1.8% progressed to severe AS. Among the 333 patients with moderate AS, 36.3% progressed to severe AS. The mean HbA1c level during follow-up showed a positive relationship with the AS progression rate (ß = 2.620; 95% confidence interval [CI] 0.732-4.507; p = 0.007); a 1%-unit increase in HbA1c was associated with a 27% higher risk of accelerated AS progression defined as △Vpeak/year values > 0.2 m/sec/year (adjusted OR = 1.267 per 1%-unit increase in HbA1c; 95% CI 1.106-1.453; p < 0.001), and HbA1c ≥ 7.0% was significantly associated with an accelerated AS progression (adjusted odds ratio = 1.524; 95% CI 1.010-2.285; p = 0.043). This association between the degree of glycemic control and AS progression rate was observed regardless of the baseline AS severity. CONCLUSION: In patients with mild to moderate AS, the presence of DM, as well as the degree of glycemic control, is significantly associated with accelerated AS progression.

Anomaly Detection Based on a 3D Convolutional Neural Network Combining Convolutional Block Attention Module Using Merged Frames.

With the recent rise in violent crime, the real-time situation analysis capabilities of the prevalent closed-circuit television have been employed for the deterrence and resolution of criminal activities. Anomaly detection can identify abnormal instances such as violence within the patterns of a specified dataset; however, it faces challenges in that the dataset for abnormal situations is smaller than that for normal situations. Herein, using datasets such as UBI-Fights, RWF-2000, and UCSD Ped1 and Ped2, anomaly detection was approached as a binary classification problem. Frames extracted from each video with annotation were reconstructed into a limited number of images of 3×3, 4×3, 4×4, 5×3 sizes using the method proposed in this paper, forming an input data structure similar to a light field and patch of vision transformer. The model was constructed by applying a convolutional block attention module that included channel and spatial attention modules to a residual neural network with depths of 10, 18, 34, and 50 in the form of a three-dimensional convolution. The proposed model performed better than existing models in detecting abnormal behavior such as violent acts in videos. For instance, with the undersampled UBI-Fights dataset, our network achieved an accuracy of 0.9933, a loss value of 0.0010, an area under the curve of 0.9973, and an equal error rate of 0.0027. These results may contribute significantly to solve real-world issues such as the detection of violent behavior in artificial intelligence systems using computer vision and real-time video monitoring.

Predicting Long-Term Mortality in Patients With Acute Heart Failure by Using Machine Learning.

BACKGROUND: High mortality rates in patients with acute heart failure (AHF) necessitate proper risk stratification. However, risk-assessment tools for long-term mortality are largely lacking. We aimed to develop a machine-learning (ML)-based risk-prediction model for long-term all-cause mortality in patients admitted for AHF. METHODS AND RESULTS: The ML model, based on boosted a Cox regression algorithm (CoxBoost), was trained with 2704 consecutive patients hospitalized for AHF (median age 73 years, 55% male, and median left ventricular ejection fraction 38%). We selected 27 input variables, including 19 clinical features and 8 echocardiographic parameters, for model development. The best-performing model, along with pre-existing risk scores (BIOSTAT-CHF and AHEAD scores), was validated in an independent test cohort of 1608 patients. During the median 32 months (interquartile range 12-54 months) of the follow-up period, 1050 (38.8%) and 690 (42.9%) deaths occurred in the training and test cohorts, respectively. The area under the receiver operating characteristic curve (AUROC) of the ML model for all-cause mortality at 3 years was 0.761 (95% CI: 0.754-0.767) in the training cohort and 0.760 (95% CI: 0.752-0.768) in the test cohort. The discrimination performance of the ML model significantly outperformed those of the pre-existing risk scores (AUROC 0.714, 95% CI 0.706-0.722 by BIOSTAT-CHF; and 0.681, 95% CI 0.672-0.689 by AHEAD). Risk stratification based on the ML model identified patients at high mortality risk regardless of heart failure phenotypes. CONCLUSIONS: The ML-based mortality-prediction model can predict long-term mortality accurately, leading to optimal risk stratification of patients with AHF.

Mildly Abnormal Lipid Levels, but Not High Lipid Variability, Are Associated With Increased Risk of Myocardial Infarction and Stroke in "Statin-Naive" Young Population A Nationwide Cohort Study.

RATIONALE: In young adults, the role of mildly abnormal lipid levels and lipid variability in the risk of atherosclerotic cardiovascular diseases remains uncertain. OBJECTIVE: To investigate the association of these abnormalities in lipid profiles with the risk of myocardial infarction (MI) and stroke in young population. METHODS AND RESULTS: From the Korean National Health Insurance Service, a nationwide population-based cohort of 1 934 324 statin-naive adults aged 20 to 39 years, with ≥3 lipid profile measurements and without a history of MI and stroke, were followed-up until the date of MI or stroke, or December 31, 2017. The primary measure of lipid variability was variability independent of the mean. Higher baseline total cholesterol, LDL-C (low-density lipoprotein-cholesterol), and triglycerides and lower HDL-C (high-density lipoprotein-cholesterol) levels were significantly associated with increased MI risk; respective adjusted hazard ratios and 95% CIs comparing the highest versus lowest quartiles were 1.35 (1.20-1.53) for total cholesterol, 1.41 (1.25-1.60) for LDL-C, 1.28 (1.11-1.47) for triglycerides, and 0.82 (0.72-0.94) for HDL-C. Adjusted analyses for deciles of lipid profiles showed that MI risk was significantly elevated among participants with total cholesterol ≥223.4 mg/dL, LDL-C ≥139.5 mg/dL, HDL-C ≤41.8 mg/dL, and triglycerides ≥200.1 mg/dL. The associations between lipid levels and stroke risk were less prominent. Multivariable-adjusted restricted cubic spline analysis demonstrated that the increase in MI risk was not exclusively driven by extreme values of lipid profiles. Similar results were obtained on sensitivity analyses of baseline lipid levels. However, associations between lipid variability and the risk of MI and stroke varied depending on the measure of lipid variability used. CONCLUSIONS: Mildly abnormal baseline lipid levels were associated with an increased future risk of atherosclerotic cardiovascular disease events, particularly MI, whereas measures of lipid variability were not. Therefore, in young adults, achieving optimal lipid levels could be valuable in the prevention of atherosclerotic cardiovascular disease.

H2FPEF Score Reflects the Left Atrial Strain and Predicts Prognosis in Patients With Heart Failure With Preserved Ejection Fraction.

BACKGROUND: The H2FPEF score is a validated algorithm for the diagnosis of heart failure with preserved ejection fraction (HFpEF). We investigated the associations of the H2FPEF score with echocardiographic parameters and prognosis in patients with HFpEF admitted for acute heart failure. METHODS AND RESULTS: In total, 4312 patients at 3 tertiary centers were identified. Among 1335 patients with HFpEF, the H2FPEF score was available in 1105 patients (39% male) with a median age of 77 years (interquartile range 69-82). The median H2FPEF score was 4 (interquartile range 3-6). Patients with higher H2FPEF scores had worse left atrial (LA) size, peak atrial longitudinal strain of the left atrium, mitral E/e' ratio, and peak tricuspid regurgitation velocity. Peak atrial longitudinal strain of the left atrium demonstrated a significant association with the H2FPEF score, in patients without atrial fibrillation and those without atrial fibrillation. After adjustment for clinical factors and echocardiographic parameters, patients with higher H2FPEF scores had a higher risk of mortality and hospitalization for heart failure, regardless of the presence of atrial fibrillation. CONCLUSIONS: The H2FPEF score reflects left atrial function in patients with HFpEF admitted for acute heart failure. This association supports the clinical usefulness of the H2FPEF score as an indicator of diastolic dysfunction, a diagnostic algorithm for HFpEF, and a prognostic factor in patients with HFpEF.

Association of physical activity with all-cause and cardiovascular mortality in 7666 adults with hypertrophic cardiomyopathy (HCM): more physical activity is better.

OBJECTIVES: Recommendations on physical activity (PA) for adults with hypertrophic cardiomyopathy (HCM) are not well established. We investigated the association of PA intensity with mortality in the general adult HCM population. METHODS: A nationwide population-based cohort of individuals with HCM who underwent health check-ups including questionnaires on PA levels were identified from the years 2009 to 2016 in the National Health Insurance Service database. Subjects who reported no PA at baseline were excluded. To estimate each individual's PA level, the PA score (PAS) was calculated based on the self-reported questionnaires, and the study population was categorised into three groups according to tertiles of PAS. The associations of PAS with all-cause and cardiovascular mortality were analysed. RESULTS: A total of 7666 participants (mean age 59.5 years, 29.9% were women) were followed up for a mean 5.3±2.0 years. All-cause and cardiovascular mortality progressively decreased from the lowest to the highest tertiles of PA intensity: 9.1% (4.7%), 8.9% (3.8%) and 6.4% (2.7%), respectively (p-for-trend=0.0144 and 0.0023, respectively). Of note, compared with the middle PA group, the highest PA group did not have an increased risk of all-cause and cardiovascular mortality (HR 0.78, (95% CI 0.63 to 0.95) and HR 0.75 (95% CI 0.54 to 1.03), respectively). All subgroup and sensitivity analyses consistently showed that all-cause and cardiovascular mortality did not increase with higher PA levels. CONCLUSIONS: Moderate-to-vigorous-intensity PA, in a middle-aged population of patients with HCM, was associated with progressive reduction of all-cause and cardiovascular mortality. The impact of vigorous-intensity PA on a younger age group requires further investigation.

Long-term Prognosis of Mild to Moderate Aortic Stenosis and Coronary Artery Disease.

BACKGROUND: There is an incomplete understanding of the natural course of mild to moderate aortic stenosis (AS). We aimed to evaluate the natural course of patients with mild to moderate AS and its association with coronary artery disease (CAD). METHODS: We retrospectively analyzed 787 patients diagnosed with mild to moderate AS using echocardiography between 2004 and 2010. Cardiac death and aortic valve replacement (AVR) for AS were assessed. RESULTS: A median follow-up period was 92 months. Compared to the general population, patients with mild to moderate AS had a higher risk of cardiac death (hazard ratio [HR], 17.16; 95% confidence interval [CI], 13.65-21.59; P < 0.001). Established CAD was detected in 22.4% and associated with a significantly higher risk of cardiac mortality (adjusted HR, 1.62; 95% CI, 1.04-2.53; P = 0.033). The risk of cardiac death was lower when patients were taking statin (adjusted HR, 0.64; 95% CI, 0.41-0.98; P = 0.041), which was clear only after 7 years. Both patients with CAD and on statin tended to undergo more AVR, but the difference was not statistically significant (the presence of established CAD; adjusted HR, 1.63; 95% CI, 0.51-3.51; P = 0.214 and the use of statin; adjusted HR, 1.86; 95% CI, 0.76-4.58; P = 0.177). CONCLUSION: Mild to moderate AS does not have a benign course. The presence of CAD and statin use may affect the long-term prognosis of patients with mild to moderate AS.

Different effects of SGLT2 inhibitors according to the presence and types of heart failure in type 2 diabetic patients.

BACKGROUND: The effects of sodium-glucose cotransporter 2 inhibitor (SGLT2i) on cardiac function are not fully understood. We investigated the changes in cardiac function in diabetic patients according to the presence and types of heart failure (HF). METHODS: We retrospectively identified 202 diabetic patients who underwent echocardiography before, and 6 to 24 months after the initiation of SGLT2i. After propensity score matching with diabetic patients without SGLT2i, the study population (n = 304) were categorized into group 1 (without HF nor SGLT2i; n = 76), group 2 (without HF and received SGLT2i; n = 78), group 3 (with HF but without SGLT2i; n = 76), and group 4 (with HF and received SGLT2i; n = 74). Changes in echocardiographic parameters were compared between these 4 groups, and between HF patients with reduced versus preserved ejection fraction (EF). RESULTS: After a median 13 months of follow-up, HF patients with SGLT2i showed a significant decrease in left ventricular end-diastolic dimension (LV-EDD; from 57.4 mm [50.0-64.9] to 53.0 mm [48.0-60.0]; p < 0.001) and improvement in LV-EF (from 36.1% [25.6-47.5] to 45.0% [34.8-56.3]; p < 0.001). LV mass index and diastolic parameters also showed improvements in HF patients with SGLT2i. The SGLT2i-induced improvements in cardiac function were more prominent in HF patients than those without HF, and in HFrEF patients than HFpEF patients. CONCLUSIONS: Use of SGLT2i improved cardiac function in diabetic patients, regardless of the presence of HF. The improvements were more prominent in HF patients, especially in those with HFrEF. These improvements in cardiac function would contribute to the clinical benefit of SGLT2i.

Therapeutic Temperature Modulation for a Critically Ill Patient with COVID-19.

We report a rapidly deteriorating coronavirus disease 2019 (COVID-19) patient, a-58-year-old woman, with severe acute respiratory distress syndrome and shock with hyperpyrexia up to 41.8°C, probably due to the cytokine storm syndrome. Considering extracorporeal membrane oxygenation (ECMO) as the last resort, we applied therapeutic temperature modulation for management of hyperpyrexia. The patient demonstrated rapid improvement in oxygenation and shock after achieving normothermia, and fully recovered from COVID-19 three weeks later. Therapeutic temperature modulation may have successfully offloaded the failing cardiorespiratory system from metabolic cost and hyperinflammation induced by hyperpyrexia. The therapeutic temperature modulation can safely be applied in a specific group of patients with cytokine storm syndrome and hyperpyrexia, which may reduce the number of patients requiring ECMO in the global medical resource shortage.

Current Key Issues in Transcatheter Aortic Valve Replacement Undergoing a Paradigm Shift.

As a new technology in the management of valvular heart disease, transcatheter aortic valve replacement (TAVR) has drawn much attention since its emergence. To date, numerous studies have investigated the safety and efficacy of TAVR in patients of various risk profiles with severe aortic stenosis (AS) and demonstrated comparable or superior outcomes of TAVR when compared with surgical aortic valve replacement (SAVR). The favorable outcomes of TAVR in inoperable patients, as well as in high- and intermediate-risk patients, are endorsed in current guidelines, and trials of low-risk patients have shown non-inferior or even superior results of TAVR than for SAVR, suggesting that the clinical indications of TAVR can be expanded to low-risk patients. Moreover, a therapeutic role of TAVR has been suggested in various aortic valve (AV) diseases, such as bicuspid AV, moderate AS with heart failure, aortic regurgitation, and bioprosthetic valve failure. In this review, we summarize the current issues of TAVR in various patient populations and discuss the expanding clinical indications of TAVR, which are driving a major paradigm shift in the management of AV disease.

Healthcare utilization, medical expenditure, and mortality in Korean patients with pulmonary hypertension.

BACKGROUND: Limited data exists regarding healthcare utilization, medical expenses, and prognosis of pulmonary hypertension (PH) according to the World Health Organization (WHO) classification. We aimed to investigate mortality risk, healthcare utilization and medical expenditure in patients with PH across the five diagnostic subgroups. METHODS: We identified 2185 patients with PH, defined as peak tricuspid regurgitation velocity > 3.4 m/sec, among the consecutive patients referred for echocardiography between 2009 and 2015. Using diagnostic codes, medical records, and echocardiographic findings, the enrolled patients were classified according to the five subgroups by WHO classification. Healthcare utilization, costs, and all-cause mortality were assessed. RESULTS: Diagnostic subgroups of PH demonstrated significantly different clinical features. During a median of 32.4 months (interquartile range, 16.2-57.8), 749 patients (34.3%) died. Mortality risk was the lowest in group II (left heart disease) and highest in group III (chronic lung disease). The etiologies of pulmonary arterial hypertension (PAH) had significant influence on the mortality risk in group I, showing the worst prognosis in PAH associated with connective tissue disease. Medical expenditure and healthcare utilization were different between the PH subgroups: groups II and V had more hospitalizations and medical expenses than other groups. Regardless of PH subgroups, the severity of PH was associated with higher mortality risk, more healthcare utilization and medical expenditure. CONCLUSIONS: Significant differences in clinical features and prognostic profiles between PH subgroups reflect the differences in pathophysiology and clinical consequences. Our findings highlight the importance of comprehensive understanding of PH according to the etiology and its severity.

Pulmonary hemodynamics and effects of phosphodiesterase type 5 inhibition in heart failure: a meta-analysis of randomized trials.

BACKGROUND: Previous studies suggested that phosphodiesterase 5 inhibitors (PDE5i) have a beneficial effect in patients with heart failure (HF), although the results were inconsistent. We performed a meta-analysis to evaluate the effect of PDE5i in HF patients, and investigated the relationship between PDE5i effects and pulmonary hemodynamics. METHOD: We searched PubMed, EMBASE and the Cochrane Library for randomized controlled trials (RCTs) that compared PDE5i with placebo in HF with reduced ejection fraction (HFrEF) or HF with preserved EF (HFpEF). PDE5i effects were interpolated according to baseline pulmonary arterial pressure (PAP) or according to changes in PAP after PDE5i treatment. RESULTS: Thirteen RCTs enrolling 898 HF patients, and two sub-analysis studies with different study outcomes, were included in the meta-analysis. Among patients with HFrEF, PDE5i improved peak VO2 (mean difference [MD], 3.76 mL/min/kg; 95% confidence interval [CI], 3.27 to 4.25; P < 0.00001), VE/VCO2 slope (MD, -6.04; 95% CI, -7.45 to -4.64; P < 0.00001), LVEF (MD, 4.30%; 95% CI, 2.18 to 6.42; P < 0.0001), and pulmonary vascular resistance (MD, -80.74 dyn·sec/cm5; 95% CI, -110.69 to -50.79; P < 0.00001). The effects of PDE5i in patients with HFpEF were heterogeneous. Meta-regression analyses indicated that the beneficial effect of PDE5i was related to the baseline PAP as well as the extent of PDE5i-mediated PAP decrease. CONCLUSION: PDE5i improved pulmonary hemodynamics and exercise capacity in patients with HFrEF, but not in HFpEF. The relationship between the benefits by PDE5i with the baseline PAP and the changes in PAP indicates the therapeutic potential of PDE5i in HF according to pulmonary hemodynamics.

Congenital heart disease at Laos Children's Hospital: Two year experience.

BACKGROUND: Management of congenital heart disease (CHD) in developing countries is challenging because of limited access to health-care facilities and socioeconomic limitations. The aim of this study was to describe the recent experience with CHD at Children's Hospital, Vientiane, Laos, the only pediatric referral hospital in the country. METHODS: From July 2013 to November 2015, 1009 echocardiograms were carried out in 797 individuals who visited Children's Hospital, in whom CHD was identified in 213. Demographic characteristics, echocardiography and age at first CHD diagnosis on echocardiogram were compared by residential area. RESULTS: Among the 213 patients, the most frequent anomalies, in descending order, were ventricular septal defect, atrial septal defect, patent ductus arteriosus, and tetralogy of Fallot. Moderate or severe CHD requiring surgery or intervention was detected in 137 patients; median age at initial diagnosis was 6.0 months (IQR, 1.5-29.8). Among those with moderate or severe CHD, 89 patients were from rural areas and 48 from the capital area. The proportion of patients from rural areas older than 1 and 3 years at diagnosis was 46.1% and 32.6%, respectively. In contrast, patients from the capital area were diagnosed at a significantly earlier age: 16.7% at age >1 year and 6.2% at age >3 years (both P < 0.001 vs rural areas). CONCLUSIONS: Diagnosis of CHD requiring surgery is delayed in Laos, especially in rural areas. Better education and training of local medical staff, and greater access to medical advice are required to improve CHD care in Laos.

Systemic Inflammation Is Associated With Coronary Artery Calcification and All-Cause Mortality in Chronic Kidney Disease.

BACKGROUND: Presence of systemic inflammation in chronic kidney disease (CKD) is associated with advanced coronary artery calcification (CAC). The prognostic significance of this association, however, is unknown. We evaluated the associations between CAC, estimated glomerular filtration rate (eGFR) and all-cause mortality, to determine whether the associations differ according to the presence of systemic inflammation. METHODS AND RESULTS: We followed 30,703 consecutive individuals who underwent CAC measurement for a median of 79 months (IQR, 65-96 months). Patients were categorized according to baseline CAC score (0, 1-99, 100-399 and ≥400), eGFR (<45, 45-59, 60-74, 75-89, 90-104, and ≥105 ml/min/1.73 m(2)) and high-sensitivity C-reactive protein (hsCRP; <2.0, and ≥2.0 mg/L). Prevalence and extent of CAC were greater in those with lower eGFR and higher hsCRP accordingly, even after adjustment. Lower eGFR was strongly associated with higher CAC score (≥400), and the association was more significant in patients with higher hsCRP. The greater CAC burden was associated with worse outcome in the CKD patients (eGFR <60 ml/min/1.73 m(2)) only in those with higher hsCRP. CONCLUSIONS: Patients with low eGFR and more extensive CAC had greater risk of mortality, and associations differed according to the presence of systemic inflammation. Among the CKD patients, coronary evaluation may be considered for those with elevated hsCRP. (Circ J 2016; 80: 1644-1652).

PDE 5 inhibition with udenafil improves left ventricular systolic/diastolic functions and exercise capacity in patients with chronic heart failure with reduced ejection fraction; A 12-week, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Impaired nitric oxide-mediated pulmonary vascular tone is commonly found in heart failure with reduced ejection fraction (HFrEF), and is associated with derangement of left ventricular (LV) hemodynamics and decreased exercise capacity, which may be reversed by PDE5 inhibitor. This study investigated the effects of a new, long-acting PDE5 inhibitor on LV hemodynamics and exercise capacity in HFrEF. METHODS: Patients with chronic HFrEF on optimal medical therapy for >30 days before enrollment were randomly assigned to placebo or udenafil at a dose of 50mg 2x/day for the first 4 weeks followed by 100mg 2x/day for the next 8 weeks. All patients underwent cardiopulmonary exercise echocardiography before and after the 12-week treatment. RESULTS: Improvement of subjective functional capacity was more frequently reported in the udenafil group (P = 0.002). Also, a higher increase in peak VO2 (Δpeak VO2, 21.6% (6.9 ~ 106.4%) vs 1.9% (-15.7 ~ 21.0%) in the placebo group, P = 0.04) and a larger decrease in ventilatory efficiency were observed in the udenafil group (Δ-6.4 ± 9.7 vs Δ1.9 ± 12.1 in the placebo group, P = 0.03). Regarding LV systolic function, the extent of increment in LV ejection fraction was significantly greater in the udenafil group (6.6 ± 6.4% vs 2.3 ± 4.8% in the placebo group, P = 0.02). In the udenafil group, an echocardiographic surrogate of LV filling pressure was more prominently decreased (P = 0.006) along with a significant reverse remodeling of left atrial volume index (57 ± 25mL at baseline to 44 ± 23 at 12th week, P = 0.04) and a progressive fall in B-type natriuretic peptide level (589 ± 679pg/mL at baseline to 220 ± 225pg/mL at 12th week, P < 0.001), indicating LV diastolic function improvement. Udenafil was well tolerated without excess of adverse events compared to placebo. CONCLUSIONS: Udenafil improves LV systolic/diastolic functions and exercise capacity in conjunction with established conventional pharmacotherapy, without significant adverse events in HFrEF.