ELUCIDATE Trial: A Single-Center Randomized Controlled Study.

BACKGROUND: Dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, is an epochal oral antidiabetic drug that improves cardiorenal outcomes. However, the effect of early dapagliflozin intervention on left ventricular (LV) remodeling in patients with type 2 diabetes free from cardiovascular disease remains unclear. METHODS AND RESULTS: The ELUCIDATE trial was a prospective, open-label, randomized, active-controlled study that enrolled 76 patients with asymptomatic type 2 diabetes with LV ejection fraction ≥50%, randomized to the dapagliflozin 10 mg/day add-on or standard-of-care group. Speckle-tracking echocardiography-based measurements of the cardiac global longitudinal strain were performed at baseline and 24 weeks after treatment initiation. Patients who received dapagliflozin had a greater reduction in LV dimension (1.68 mm [95% CI, 0.53-2.84]; P=0.005), LV end-systolic volume (5.51 mL [95% CI, 0.86-10.17]; P=0.021), and LV mass index (4.25 g/m2.7 [95% CI, 2.42-6.09]; P<0.0001) compared with standard of care in absolute mean differences. Dapagliflozin add-on therapy led to a significant LV global longitudinal strain increment (0.74% [95% CI, 1.00-0.49]; P<0.0001) and improved LV systolic and early diastolic strain rates (0.27/s [95% CI, 0.17-0.60]; and 0.11/s [95% CI, 0.06-0.16], respectively; both P<0.0001) but not in global circumferential strain. No significant changes were found in insulin resistance, NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, or other biomarkers at 6 months after the dapagliflozin administration. CONCLUSIONS: Dapagliflozin add-on therapy could lead to more favorable cardiac remodeling accompanied by enhanced cardiac mechanical function among patients with asymptomatic type 2 diabetes. Our findings provide evidence of the efficacy of dapagliflozin use for the primary prevention of diabetic cardiomyopathy. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03871621.

Sodium Glucose Transporter 2 Inhibitors Versus Metformin on Cardiovascular and Renal Outcomes in Patients With Diabetes With Low Cardiovascular Risk: A Nationwide Cohort Study.

BACKGROUND: This study investigated whether initial SGLT2 (sodium-glucose cotransporter 2) inhibitor-based treatment is superior to metformin-based regimens as a primary prevention strategy among low-risk patients with diabetes. METHODS AND RESULTS: In this nationwide cohort study, a total of 38 496 patients with diabetes with low cardiovascular risk were identified (age 62.0±11.6 years, men 50%) from January 1 to December 31, 2016. Patients receiving SGLT2 inhibitors-based and metformin-based regimens were 1:2 matched by propensity score. Study outcomes included all-cause mortality, cardiovascular death, hospitalization for heart failure, stroke, and progression to end-stage renal disease. Compared with 1928 patients receiving metformin-based regimens, 964 patients receiving SGLT2 inhibitor-based regimens had similar all-cause mortality (hazard ratio [HR], 0.75 [95% CI, 0.51-1.12]), cardiovascular death (HR, 0.69 [95% CI, 0.25-1.89]), hospitalization for heart failure (HR, 1.06 [95% CI, 0.59-1.92]), stroke (HR, 0.78 [95% CI, 0.48-1.27]), and progression to end-stage renal disease (HR, 0.88 [95% CI, 0.32-2.39]). However, SGLT2 inhibitors were associated with a lower risk of all-cause mortality (HR, 0.47 [95% CI, 0.23-0.99]; P for interaction=0.008) and progression to end-stage renal disease (HR, 0.22 [95% CI, 0.06-0.82]; P for interaction=0.04) in patients under the age of 65. CONCLUSIONS: In comparison to metformin-based regimens, SGLT2 inhibitor-based regimens showed a similar risk of all-cause mortality and adverse cardiorenal events. SGLT2 inhibitors might be considered as first-line therapy in select low-risk patients, for example, younger patients with diabetes.

Prognostic value of left ventricular and left atrial strain imaging in moderate to severe aortic stenosis: Insights from an Asian population.

BACKGROUND: Data regarding the prognostic value of left atrial (LA) strain in aortic stenosis (AS) is scarce, especially in Asian population and moderate AS. METHOD: Left ventricular global longitudinal strain (LVGLS), LA reservoir strain (LASr), conduit strain (LAScd), and contractile strain (LASct) were measured using automated speckle-tracking echocardiography in consecutive patients with moderate or severe AS. The primary endpoint was a composite of all-cause death (ACD) and major adverse cardiovascular events (MACE; myocardial infarction, syncope, and heart failure hospitalization). RESULTS: Of 712 patients (mean age, 78 ± 12 years; 370 [52%] moderate AS; 342 [48%] severe AS), average LV ejection fraction (LVEF) was 68 with SD of 12%. At a median follow-up of 18 months (interquartile range, 11-26 months), the primary endpoint occurred in 93 patients (60 deaths and 35 MACEs) and 221 patients underwent surgical or transcatheter aortic valve replacement (AVR). In the entire cohort, separate multivariable models adjusted for age, Charlson index, symptomatic status, time-dependent AVR, AS-severity, LA volume index and LVEF demonstrated that only LASr was associated with MACE+ACD (Hazard ratio, 0.97; P = 0.014). Subgroup analysis for MACE+ACD demonstrated consistent prognostication for LASr in moderate and severe AS; LVGLS was prognostic only in severe AS (all P ≤ 0.023). The optimal MACE+ACD cutoff for LASr from spline curves was 21.3%. Adjusted Kaplan-Meier curves demonstrated better event-free survival in patients with LASr >21.3% versus those with LASr ≤21.3% (P = 0.04). CONCLUSIONS: In both moderate and severe AS, only LASr robustly predicted outcomes; thus, including LASr in the AS staging algorithm should be considered.

Transdermal Nicotine Patch Increases the Number and Function of Endothelial Progenitor Cells in Young Healthy Nonsmokers without Adverse Hemodynamic Effects.

Transdermal nicotine patches (TNPs), administering nicotine into the bloodstream through skin, have been widely used as nicotine replacement therapy, and exposure to nicotine can be detected by measurement of plasma cotinine concentration. In animal studies, nicotine treatment could increase the number of endothelial progenitor cells (EPCs), but the effect of TNPs on circulating EPCs and their activity in humans remained unclear. This study aimed to explore the influence of TNPs on circulating EPCs with surface markers of CD34, CD133, and/or KDR, and colony-forming function plus migration activity of early EPCs derived from cultured peripheral blood mononuclear cells before and after TNP treatments in young healthy nonsmokers. In parallel, pulse wave analysis (PWA) was applied to evaluate the vascular effect of TNP treatments. Twenty-one participants (25.8 ± 3.6 years old, 10 males) used TNP (nicotine: 4.2 mg/day) for 7 consecutive days. During the treatment, the CD34+ EPCs progressively increased in number. In addition, the number of EPCs positive for CD34/KDR, CD133, and CD34/CD133 were also increased on day 7 of the treatment. Furthermore, the early EPC colony-forming function and migration activity were increased with the plasma cotinine level positively correlating with change in colony-forming unit number. PWA analyses on day 7, compared with pretreatment, did not show significant change except diastolic pressure time index, which was prolonged and implied potential vascular benefit. In conclusion, 7-day TNP treatments could be a practical strategy to enhance angiogenesis of circulating EPCs to alleviate tissue ischemia without any hemodynamic concern.

Efficacy of Sacubitril-Valsartan on Survival and Cardiac Remodeling in Hypotensive Heart Failure With Reduced Ejection Fraction: A Multicenter Study.

OBJECTIVE: To investigate whether hypotensive patients diagnosed with heart failure and reduced ejection fraction (HFrEF) might benefit from angiotensin receptor-neprilysin inhibitors (ARNis) in real-world practice because patients with baseline systolic blood pressure (SBP) of less than 100 mm Hg have been excluded from landmark trials. PATIENTS AND METHODS: In this multicenter study conducted between January 1, 2013, and December 31, 2021, a total of 7562 symptomatic patients with HFrEF were enrolled and grouped by SBP (hypotension was defined as an SBP of less than 100 mm Hg) and ARNi use as follows: group 1, hypotensive/non-ARNi users (n=484); group 2, hypotensive/ARNi users (n=308); group 3, nonhypotensive/non-ARNi users (n=4560); and group 4, nonhypotensive/ARNi users (n=2210). Inverse probability of treatment weighting was used to balance baseline characteristics for survival analysis. RESULTS: Diverse baseline characteristics and lower rates of medication use were found among non-ARNi users compared with ARNi users. Hypotensive/ARNi users had lower ARNi initiation doses than nonhypotensive/ARNi users. We observed significantly lower mortality, composite heart failure hospitalization, and CV death for hypotensive/ARNi and the other 2 nonhypotensive groups (groups 3 and 4) during a median follow-up of 3.43 years (all P<.05), with a similar effect on reverse remodeling for the hypotensive/ARNi group compared with the hypotensive/non-ARNi group. The event-free survival benefits of ARNi vs renin-angiotensin system inhibitors were consistent with the lower boundary of SBP for clinical benefits found until 88 mm Hg (spline curves) after inverse probability of treatment weighting. CONCLUSION: Patients with HFrEF and hypotension may still benefit from ARNi treatment. Patients with hypotensive HFrEF should not be routinely excluded from ARNi use in a real-world setting.

Taiwan Society of Cardiology Heart Failure Registry 2020: Rationale and Design.

Background: Heart failure (HF) is a significant public health problem worldwide. Death and rehospitalization rates are similar across different HF phenotypes. However, the existing Taiwanese HF registries mainly enrolled inpatients with HF and reduced ejection fraction (HFrEF) before 2019, so their results may not apply to outpatients or patients with HF with mildly reduced ejection fraction (HFmrEF) and HF with preserved ejection fraction (HFpEF) phenotypes. Methods: The Taiwan Society of Cardiology Heart Failure Registry 2020 is a prospective, multicenter, observational registry that will enroll patients with HF from 27 hospitals in Taiwan between 2020 and 2022 and will be followed for two years. Patients eligible for enrollment include those admitted due to acute decompensated heart failure or outpatients with a history of hospitalization for heart failure within the past six months. The registry will collect patient demographics, medical history, HF diagnosis, medication use, examination results, and comorbidities. The registry plans to enroll 3,370 patients, with the distribution of HFrEF/HFmrEF/HFpEF as 59%/13%/28%. Follow-up intervals will occur every six months for up to two years to monitor clinical outcomes and major cardiac interventions. The registry will conclude in December 2024. Conclusions: The Taiwan Society of Cardiology Heart Failure Registry 2020 is a comprehensive and meticulous effort to demonstrate the epidemiology, adherence to guidelines, clinical outcomes, and disease progression of Taiwanese patients with HF in contemporary clinical practice.

2024 Guidelines of the Taiwan Society of Cardiology for the Diagnosis and Treatment of Heart Failure with Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a multi-organ systemic syndrome that involves cardiac and extra-cardiac pathophysiological abnormalities. Its growing prevalence causes a major public concern worldwide. HFpEF is usually associated with multiple comorbidities, and non-cardiovascular death is common in patients with HFpEF. In Asia, patients with HFpEF has a younger age, higher prevalence of diabetes and chronic kidney disease than Western countries. A 2-step diagnostic algorithm is recommended in this guideline. In the first step, the diagnosis of HFpEF can be made if patients have symptoms and/or signs of heart failure, left ventricular ejection fraction ≥ 50%, increased natriuretic peptide, and objective evidence of left atrial or left ventricular abnormalities or raised left ventricular filling pressure. If diagnosis is still uncertain, invasive or noninvasive stress test can be performed in the second step. Comorbidities need to be controlled in HFpEF. Weight reduction for obesity and supervised exercise training are recommended for HFpEF. For pharmacological therapy, diuretic is used to relieve congestion and sodium-glucose cotransporter 2 inhibitor, empagliflozin or dapagliflozin, is recommended to improve prognosis of HFpEF. The research on HFpEF is advancing at a rapid pace. It is expected that newer modalities for diagnosis and management of HFpEF could appear in the near future.

Preclinical systolic dysfunction relating to ankle-brachial index among high-risk PAD population with preserved left ventricular ejection fraction.

Peripheral artery disease (PAD) shares common clinical risk factors, for example, endothelial dysfunction, with preserved ejection fraction (LVEF) heart failure (HFpEF). Whether PAD is associated with preclinical systolic dysfunction and higher HF risk among individuals presenting preserved LVEF remains uncertain. We retrospectively included outpatients with at least one known or established cardiovascular (CV) risk factor with LVEF ≥ 50%. Patients were categorized into high risk and low risk of developing PAD (PAD vs Non-PAD) by ankle-brachial index (ABI) (≤ 0.90 or > 1.4) and further stratified based on their history of HFpEF (HFpEF vs. Non-HFpEF), resulting in the formation of four distinct strata. Preclinical systolic dysfunction was defined using dedicated speckle-tracking algorithm. A total of 2130 consecutive patients were enrolled in the study, with a median follow-up of 4.4 years. The analysis revealed a higher prevalence of high risk of developing PAD in patients with HFpEF compared to those without HFpEF (25.1% vs. 9.4%). Both high risk of developing PAD and HFpEF were independently associated with preclinical systolic dysfunction (global longitudinal strain, GLS ≥ - 18%) (odds ratio, OR: 1.38; 95% confidence interval, CI: 1.03-1.86). In comparison to patients at low risk of developing PAD without HFpEF (Non-PAD/Non-HFpEF group), those categorized as having a high risk of developing PAD with HFpEF (PAD/HFpEF group) exhibited the most impaired GLS and a heightened susceptibility to heart failure hospitalization (hazard ratio, HR: 6.51; 95% CI: 4.43-9.55), a twofold increased risk of all-cause mortality (HR: 2.01; 95% CI: 1.17-3.38), cardiovascular mortality (HR: 2.44; 95% CI: 1.08-5.51), and non-cardiovascular mortality (HR: 1.78; 95% CI: 0.82-3.84). A high risk of developing PAD was strongly linked to impaired preclinical systolic function and an increased likelihood for subsequent hospitalization for HF, all-cause mortality, CV mortality and non-CV mortality. There is a clear need for preventive strategies aimed at reducing hospitalizations for HF and mortality in this high-risk population.

Expert recommendations for the management of iron deficiency in patients with heart failure in Asia.

BACKGROUND: Iron deficiency is a common comorbidity in heart failure (HF) and is independently associated with a worse quality-of-life and exercise capacity, as well as increased risk of hospitalization, regardless of anemia status. Although international guidelines have provided recommendations for the management of iron deficiency in patients with HF, guidelines in Asia are less established, and practical use of guidelines for management of iron deficiency is limited in the region. METHODS: A panel comprising cardiologists from China, Hong Kong, India, Japan, Malaysia, Pakistan, Philippines, Singapore, South Korea, Taiwan, and Thailand convened to share insights and provide guidance for the optimal management of iron deficiency in patients with HF, tailored for the Asian community. RESULTS: Expert opinions were provided for the screening, diagnosis, treatment and monitoring of iron deficiency in patients with HF. It was recommended that all patients with HF with reduced ejection fraction should be screened for iron deficiency, and iron-deficient patients should be treated with intravenous iron. Monitoring of iron levels in patients with HF should be carried out once or twice yearly. Barriers to the management of iron deficiency in patients with HF in the region include low awareness of iron deficiency amongst general physicians, lack of reimbursement for screening and treatment, and lack of proper facilities for administration of intravenous iron. CONCLUSIONS: These recommendations provide a structured approach to the management of iron deficiency in patients with HF in Asia.

External validation of a deep learning algorithm for automated echocardiographic strain measurements.

Aims: Echocardiographic strain imaging reflects myocardial deformation and is a sensitive measure of cardiac function and wall-motion abnormalities. Deep learning (DL) algorithms could automate the interpretation of echocardiographic strain imaging. Methods and results: We developed and trained an automated DL-based algorithm for left ventricular (LV) strain measurements in an internal dataset. Global longitudinal strain (GLS) was validated externally in (i) a real-world Taiwanese cohort of participants with and without heart failure (HF), (ii) a core-lab measured dataset from the multinational prevalence of microvascular dysfunction-HF and preserved ejection fraction (PROMIS-HFpEF) study, and regional strain in (iii) the HMC-QU-MI study of patients with suspected myocardial infarction. Outcomes included measures of agreement [bias, mean absolute difference (MAD), root-mean-squared-error (RMSE), and Pearson's correlation (R)] and area under the curve (AUC) to identify HF and regional wall-motion abnormalities. The DL workflow successfully analysed 3741 (89%) studies in the Taiwanese cohort, 176 (96%) in PROMIS-HFpEF, and 158 (98%) in HMC-QU-MI. Automated GLS showed good agreement with manual measurements (mean ± SD): -18.9 ± 4.5% vs. -18.2 ± 4.4%, respectively, bias 0.68 ± 2.52%, MAD 2.0 ± 1.67, RMSE = 2.61, R = 0.84 in the Taiwanese cohort; and -15.4 ± 4.1% vs. -15.9 ± 3.6%, respectively, bias -0.65 ± 2.71%, MAD 2.19 ± 1.71, RMSE = 2.78, R = 0.76 in PROMIS-HFpEF. In the Taiwanese cohort, automated GLS accurately identified patients with HF (AUC = 0.89 for total HF and AUC = 0.98 for HF with reduced ejection fraction). In HMC-QU-MI, automated regional strain identified regional wall-motion abnormalities with an average AUC = 0.80. Conclusion: DL algorithms can interpret echocardiographic strain images with similar accuracy as conventional measurements. These results highlight the potential of DL algorithms to democratize the use of cardiac strain measurements and reduce time-spent and costs for echo labs globally.

Investigation of the Therapeutic Potential of Organic Nitrates in Mortality Reduction Following Acute Myocardial Infarction in Hyperlipidemia Patients: A Population-Based Cohort Study.

BACKGROUND: Dyslipidemia is a known risk factor for cardiac dysfunction, and lipid-lowering therapy with statins reduces symptoms and reduces hospitalization related to left ventricular heart failure. Acute myocardial infarction (AMI) is a cause of morbidity and mortality worldwide. In this study, we aimed to determine the real-world AMI treatment drug combination used in Taiwan by using the NHI database to understand the treatment outcomes of current clinical medications prescribed for hyperlipidemia patients with AMI. METHODS: Using the NHI Research Database (NHIRD), we conducted a retrospective cohort study that compared different treatments for AMI in hyperlipidemia patients in the period from 2016 to 2018. We compared the survival outcomes between those treated with and without organic nitrates in this cohort. RESULTS: We determined that most hyperlipidemia patients were aged 61-70 y (29.95-31.46% from 2016 to 2018), and the annual AMI risk in these patients was <1% (0.42-0.68% from 2016 to 2018). The majority of hyperlipidemia patients with AMI were women, and 25.64% were aged 61-70 y. Receiving organic nitrates was associated with lower all-cause mortality rates (HR, 95% CI, p-value = 0.714, 0.674-0.756, p < 0.0001). After multivariate analysis, the overall survival in four groups (beta-blockers, beta-blocker + diuretics, diuretics, and others) receiving an organic nitrate treatment was significantly higher than in the groups that were not treated with organic nitrates (beta-blockers HR = 0.536, beta-blocker + diuretics HR = 0.620, diuretics HR = 0.715, and others HR = 0.690). CONCLUSIONS: The survival benefit was significantly greater in patients treated with organic nitrates than in those treated without organic nitrates, especially when combined with diuretics. A combination of organic nitrates could be a better treatment option for hyperlipidemia patients with AMI.

Recommended assessment and management of sleep disordered breathing in patients with atrial fibrillation, hypertension and heart failure: Taiwan Society of Cardiology/Taiwan Society of sleep Medicine/Taiwan Society of pulmonary and Critical Care Medicine joint consensus statement.

Sleep disordered breathing (SDB) is highly prevalent and may be linked to cardiovascular disease in a bidirectional manner. The Taiwan Society of Cardiology, Taiwan Society of Sleep Medicine and Taiwan Society of Pulmonary and Critical Care Medicine established a task force of experts to evaluate the evidence regarding the assessment and management of SDB in patients with atrial fibrillation (AF), hypertension and heart failure with reduced ejection fraction (HFrEF). The GRADE process was used to assess the evidence associated with 15 formulated questions. The task force developed recommendations and determined strength (Strong, Weak) and direction (For, Against) based on the quality of evidence, balance of benefits and harms, patient values and preferences, and resource use. The resulting 11 recommendations are intended to guide clinicians in determining which the specific patient-care strategy should be utilized by clinicians based on the needs of individual patients.

Taiwan Association for the Study of the Liver-Taiwan Society of Cardiology Taiwan position statement for the management of metabolic dysfunction- associated fatty liver disease and cardiovascular diseases.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is an increasingly common liver disease worldwide. MAFLD is diagnosed based on the presence of steatosis on images, histological findings, or serum marker levels as well as the presence of at least one of the three metabolic features: overweight/obesity, type 2 diabetes mellitus, and metabolic risk factors. MAFLD is not only a liver disease but also a factor contributing to or related to cardiovascular diseases (CVD), which is the major etiology responsible for morbidity and mortality in patients with MAFLD. Hence, understanding the association between MAFLD and CVD, surveillance and risk stratification of MAFLD in patients with CVD, and assessment of the current status of MAFLD management are urgent requirements for both hepatologists and cardiologists. This Taiwan position statement reviews the literature and provides suggestions regarding the epidemiology, etiology, risk factors, risk stratification, nonpharmacological interventions, and potential drug treatments of MAFLD, focusing on its association with CVD.

Clinical Features of Heart Failure With Normal Ejection Fraction: Insights From the ASIAN-HF Registry.

Background: Heart failure and left ventricular ejection fraction in the normal range (HFnEF) (left ventricular ejection fraction [LVEF] of ≥55% for men and ≥60% for women) is understudied. Objectives: The authors aimed to characterize patients with HFnEF compared with those with preserved (≥50%) yet below the normal LVEF. Methods: In an Asian HF registry, clinical characteristics, echocardiographic features, and outcomes were compared across: 1) HFnEF; 2) heart failure with preserved left ventricular ejection fraction (HFpEF) (LVEF of ≥50%) and below normal LVEF; and 3) community-based controls without HF. Cluster analysis of echocardiographic parameters was performed and validated in an external cohort. Results: Among 1,765 patients with HFpEF (age 68 ± 12 years; 50% women), 1,313 (74.4%) had HFnEF. Compared with patients with HFpEF and below normal LVEF, patients with HFnEF had less coronary artery disease (33.7% vs 27.9%), greater LV wall thickness, and higher stroke volume, but similar 2-year age-adjusted all-cause mortality (HR: 0.8; 95% CI: 0.6-1.2). Five echocardiographic clusters with similar 2-year mortality were identified: 1) normal LV (normal structure despite increased filling pressure; least comorbidities) in 25%; 2) restrictive (smallest stroke volume; predominantly elderly women) in 26%; 3) hypertrophic (most concentric hypertrophy; more men) in 25%; 4) high output (greatest stroke volume; predominantly obese younger men) in 10%; and 5) atrial dominant (most left atrial myopathy; mainly elderly women with multiple comorbidities) in 10%. Similar patterns were found in the validation cohort. Conclusions: The majority of patients with HFpEF had normal LVEF, which consists of patients with different patterns of cardiac features and clinical characteristics. Results may carry implications for targeted treatment approaches in HFpEF.

Effects of canagliflozin on cardiac remodeling and hemodynamic parameters in patients with type 2 diabetes mellitus.

Sodium-glucose cotransporter type 2 (SGLT2) inhibitors have demonstrated to reduce cardiovascular risk in patients with type 2 diabetes mellitus (T2DM) in large trials independent of glycemic control. The mechanisms of this cardioprotective property remain uncertain. Evidence suggests positive hemodynamic changes and favorable cardiac remodeling contributing to the clinical outcomes but results were conflicting. We aim to investigate the potential impact on hemodynamic parameters, cardiac structure and functions. This prospective observational study included T2DM patients receiving canagliflozin 100 mg per day in addition to their antidiabetic treatment. We analyzed hemodynamic parameters assessed by echocardiographic measurements and impedance cardiography (ICG) to evaluate systolic and diastolic functions from baseline to 24 weeks after treatment. A total of 47 patients (25 males and 22 females) averaging 64.6 ± 10.9 years had a significant reduction in HbA1c, body weight, and systolic blood pressure. Hematocrit increased significantly, while NT-proBNP remained unchanged. E/e', left atrium (LA) volume, and LA stiffness were reduced, while left ventricle (LV) global longitudinal strain (GLS) and LA strain rates increased at 24 weeks by conventional and speckle tracking echocardiography. LV mass and ejection fraction showed no differences. ICG suggested significant improvement in hemodynamic parameters with increased stroke volume index and cardiac output index and decreased systemic vascular resistance index at 12 and 24 weeks. Canagliflozin improved hemodynamic parameters and had a favorable impact on LA and LV reverse remodeling. These changes may explain the beneficial effect on cardiovascular outcomes in large clinical trials.

Increased risk of chronic fatigue syndrome following infection: a 17-year population-based cohort study.

BACKGROUND: Previous serological studies have indicated an association between viruses and atypical pathogens and Chronic Fatigue Syndrome (CFS). This study aims to investigate the correlation between infections from common pathogens, including typical bacteria, and the subsequent risk of developing CFS. The analysis is based on data from Taiwan's National Health Insurance Research Database. METHODS: From 2000 to 2017, we included a total of 395,811 cases aged 20 years or older newly diagnosed with infection. The cases were matched 1:1 with controls using a propensity score and were followed up until diagnoses of CFS were made. RESULTS: The Cox proportional hazards regression analysis was used to estimate the relationship between infection and the subsequent risk of CFS. The incidence density rates among non-infection and infection population were 3.67 and 5.40 per 1000 person-years, respectively (adjusted hazard ratio [HR] = 1.5, with a 95% confidence interval [CI] 1.47-1.54). Patients infected with Varicella-zoster virus, Mycobacterium tuberculosis, Escherichia coli, Candida, Salmonella, Staphylococcus aureus and influenza virus had a significantly higher risk of CFS than those without these pathogens (p < 0.05). Patients taking doxycycline, azithromycin, moxifloxacin, levofloxacin, or ciprofloxacin had a significantly lower risk of CFS than patients in the corresponding control group (p < 0.05). CONCLUSION: Our population-based retrospective cohort study found that infection with common pathogens, including bacteria, viruses, is associated with an increased risk of developing CFS.

Relation of early-stage renal insufficiency and cardiac structure and function in a large population of asymptomatic Asians: a cross-sectional cohort analysis.

Background: Few studies have addressed early-stage kidney disease and preclinical cardiac structural and functional abnormalities from a large-scale Asian population. Further, the extent to which measures of myocardial function and whether these associations may vary by testing various formulas of renal insufficiency remains largely unexplored. Objective: To explore the associations among renal function, proteinuria, and left ventricular (LV) structural and diastolic functional alterations. Design: A cross-sectional, retrospective cohort study. Setting: Registered data from a cardiovascular health screening program at MacKay Memorial Hospital from June 2009 to December 2012. Participants: Asymptomatic individuals. Measurements: Renal function was evaluated in terms of estimated glomerular filtration rate (eGFR) by both MDRD and CKD-EPI formulas and severity of proteinuria, which were further related to cardiac structure, diastolic function (including LV e' by tissue Doppler), and circulating N-terminal pro-brain natriuretic peptide (NT-proBNP) level. Results: Among 4942 participants (65.8% men, mean age 49.4 ± 11.2 years), the mean CKD-EPI/MDRD eGFR was 90.6 ± 15.7 and 88.5 ± 16.9 ml/min/1.73m2, respectively. Lower eGFR, estimated either by the MDRD or CKD-EPI method, and higher proteinuria were significantly associated with lower LV e' and higher NT-proBNP (all p<0.05) even after adjusting for clinical covariates. In general, lower eGFR estimated by CKD-EPI and MDRD displayed similar impacts on worsening e' and NT-proBNP, rather than E/e', in multivariate models. Finally, lower LV e' or higher composite diastolic score, rather than E/e', demonstrated remarkable interaction with eGFR level estimated by either CKD-EPI or MDRD on circulating NT-proBNP level (p interaction <0.05). Limitations: Proteinuria was estimated using a urine dipstick rather than more accurately by the urine protein-to-creatinine ratio. Also, pertaining drug history and clinical hard outcomes were lacking. Conclusion: Both clinical estimate of renal insufficiency by eGFR or proteinuria, even in a relatively early clinical stage, were tightly linked to impaired cardiac diastolic relaxation and circulating NT-proBNP level. Elevation of NT-proBNP with worsening renal function may be influenced by impaired myocardial relaxation.

Penalized Model-Based Unsupervised Phenomapping Unravels Distinctive HFrEF Phenotypes With Improved Outcomes Discrimination From Sacubitril/Valsartan Treatment Independent of MAGGIC Score.

Background The angiotensin receptor-neprilysin inhibitor (LCZ696) has emerged as a promising pharmacological intervention against renin-angiotensin system inhibitor in reduced ejection fraction heart failure (HFrEF). Whether the therapeutic benefits may vary among heterogeneous HFrEF subgroups remains unknown. Methods and Results This study comprised a pooled 2-center analysis including 1103 patients with symptomatic HFrEF with LCZ696 use and another 1103 independent HFrEF control cohort (with renin-angiotensin system inhibitor use) matched for age, sex, left ventricular ejection fraction, and comorbidity conditions. Three main distinct phenogroup clusterings were identified from unsupervised machine learning using 29 clinical variables: phenogroup 1 (youngest, relatively lower diabetes prevalence, highest glomerular filtration rate with largest left ventricular size and left ventricular wall stress); phenogroup 2 (oldest, lean, highest diabetes and vascular diseases prevalence, lowest highest glomerular filtration rate with smallest left ventricular size and mass), and phenogroup 3 (lowest clinical comorbidity with largest left ventricular mass and highest hypertrophy prevalence). During the median 1.74-year follow-up, phenogroup assignment provided improved prognostic discrimination beyond Meta-Analysis Global Group in Chronic Heart Failure risk score risk score (all net reclassification index P<0.05) with overall good calibrations. While phenogroup 1 showed overall best clinical outcomes, phenogroup 2 demonstrated highest cardiovascular death and worst renal end point, with phenogroup 3 having the highest all-cause death rate and HF hospitalization among groups, respectively. These findings were broadly consistent when compared with the renin-angiotensin system inhibitor control as reference group. Conclusions Phenomapping provided novel insights on unique characteristics and cardiac features among patients with HFrEF with sacubitril/valsartan treatment. These findings further showed potentiality in identifying potential sacubitril/valsartan responders and nonresponders with improved outcome discrimination among patients with HFrEF beyond clinical scoring.