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.

Early detection of myocardial ischemia in resting ECG: analysis by HHT.

BACKGROUND: Exercise electrocardiography (ECG) is a noninvasive test aiming at producing ischemic changes. However, resting ECG cannot be adopted in diagnosing myocardial ischemia till ST-segment depressions. Therefore, this study aimed to detect myocardial energy defects in resting ECG using the Hilbert-Huang transformation (HHT) in patients with angina pectoris. METHODS: Electrocardiographic recordings of positive exercise ECG by performing coronary imaging test (n = 26) and negative exercise ECG (n = 47) were collected. Based on the coronary stenoses severity, patients were divided into three categories: normal, < 50%, and ≥ 50%. During the resting phase of the exercise ECG, all 10-s ECG signals are decomposed by HHT. The RT intensity index, composed of the power spectral density of the P, QRS, and T components, is used to estimate the myocardial energy defect. RESULTS: After analyzing the resting ECG using HHT, the RT intensity index was significantly higher in patients with positive exercise ECG (27.96%) than in those with negative exercise ECG (22.30%) (p < 0.001). In patients with positive exercise ECG, the RT intensity index was gradually increasing with the severity of coronary stenoses: 25.25% (normal, n = 4), 27.14% (stenoses < 50%, n = 14), and 30.75% (stenoses ≥ 50%, n = 8). The RT intensity index of different coronary stenoses was significantly higher in patients with negative exercise ECG, except for the normal coronary imaging test. CONCLUSIONS: Patients with coronary stenoses had a higher RT index at the resting stage of exercise ECG. Resting ECG analyzed using HHT could be a method for the early detection of myocardial ischemia.

The Removal, Excision, Sterilization, and Quarantine (RESQ) Method is a Feasible Alternative Treatment for Cardiac Implantable Electronic Device Infections.

Background: Current guidelines recommend that all infected cardiac implantable electronic devices (CIEDs) should be removed. However, financial or anatomical concerns can lead to management of infection with simple debridement, as opposed to complete removal. In this observational study, we report the outcomes of our modified procedure for this real-world dilemma. Methods and Results: The Quarantine (RESQ) method is characterized as follows: the removal (R) of all non-essential foreign materials, including old sutures and leads; the excision (E) of all non-viable, chronically inflamed, granulation, or scar tissue; the sterilization (S) of the remaining generator; and the quarantine (Q) of a new pocket in the sub-muscular layer for reimplantation. From a review of electronic medical records, 30 patients were selected and divided into three groups according to the intervention used: RESQ (n = 9) in group A, simple debridement (n = 16) in group B, and guideline-recommended replacement (n = 5) in group C. Patient baseline characteristics were similar between the groups. After analyzing the proportion of patients that were free from infection one year following their respective interventions, we found that group A performed better than group B (100% and 31.2% infection-free, respectively, p = 0.001), and was comparable to group C (both 100% infection-free, p = not applicable). Conclusions: The RESQ method is a feasible and beneficial alternative for selected patients with CIED infections who are unable to receive a generator replacement according to the recommended guideline.

2023 Guidelines of the Taiwan Society of Cardiology on the Diagnosis and Management of Chronic Coronary Syndrome.

Coronary artery disease (CAD) covers a wide spectrum from persons who are asymptomatic to those presenting with acute coronary syndromes (ACS) and sudden cardiac death. Coronary atherosclerotic disease is a chronic, progressive process that leads to atherosclerotic plaque development and progression within the epicardial coronary arteries. Being a dynamic process, CAD generally presents with a prolonged stable phase, which may then suddenly become unstable and lead to an acute coronary event. Thus, the concept of "stable CAD" may be misleading, as the risk for acute events continues to exist, despite the use of pharmacological therapies and revascularization. Many advances in coronary care have been made, and guidelines from other international societies have been updated. The 2023 guidelines of the Taiwan Society of Cardiology for CAD introduce a new concept that categorizes the disease entity according to its clinical presentation into acute or chronic coronary syndromes (ACS and CCS, respectively). Previously defined as stable CAD, CCS include a heterogeneous population with or without chest pain, with or without prior ACS, and with or without previous coronary revascularization procedures. As cardiologists, we now face the complexity of CAD, which involves not only the epicardial but also the microcirculatory domains of the coronary circulation and the myocardium. New findings about the development and progression of coronary atherosclerosis have changed the clinical landscape. After a nearly 50-year ischemia-centric paradigm of coronary stenosis, growing evidence indicates that coronary atherosclerosis and its features are both diagnostic and therapeutic targets beyond obstructive CAD. Taken together, these factors have shifted the clinicians' focus from the functional evaluation of coronary ischemia to the anatomic burden of disease. Research over the past decades has strengthened the case for prevention and optimal medical therapy as central interventions in patients with CCS. Even though functional capacity has clear prognostic implications, it does not include the evaluation of non-obstructive lesions, plaque burden or additional risk-modifying factors beyond epicardial coronary stenosis-driven ischemia. The recommended first-line diagnostic tests for CCS now include coronary computed tomographic angiography, an increasingly used anatomic imaging modality capable of detecting not only obstructive but also non-obstructive coronary plaques that may be missed with stress testing. This non-invasive anatomical modality improves risk assessment and potentially allows for the appropriate allocation of preventive therapies. Initial invasive strategies cannot improve mortality or the risk of myocardial infarction. Emphasis should be placed on optimizing the control of risk factors through preventive measures, and invasive strategies should be reserved for highly selected patients with refractory symptoms, high ischemic burden, high-risk anatomies, and hemodynamically significant lesions. These guidelines provide current evidence-based diagnosis and treatment recommendations. However, the guidelines are not mandatory, and members of the Task Force fully realize that the treatment of CCS should be individualized to address each patient's circumstances. Ultimately, the decision of healthcare professionals is most important in clinical practice.

2023 Consensus of Taiwan Society of Cardiology on the Pharmacological Treatment of Chronic Heart Failure.

The prevalence of heart failure is increasing, causing a tremendous burden on health care systems around the world. Although mortality rate of heart failure has been significantly reduced by several effective agents in the past 3 decades, yet it remains high in observational studies. More recently, several new classes of drugs emerged with significant efficacy in reducing mortality and hospitalization in chronic heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). To integrate these effective therapies and prioritize them in the management of Asian patients, Taiwan Society of Cardiology has recently appointed a working group to formulate a consensus of pharmacological treatment in patients with chronic heart failure. Based on most updated information, this consensus provides rationales for prioritization, rapid sequencing, and in-hospital initiation of both foundational and additional therapies for patients with chronic heart failure.

Preprocedural features of patients under antihypertensive drugs may help identify responders to renal denervation: a hypothesis-generating study.

BACKGROUND: Renal denervation (RDN) is effective to lower systolic blood pressure (SBP) in essential hypertension. However, patient selection under medications remains an important unmet clinical need. METHODS: This multicenter study aimed at observing whether preprocedural features associated with increased renin-angiotensin-aldosterone activity influence RDN response. This study enrolled the patients who underwent RDN for uncontrolled hypertension. Medical records were reviewd and patients were divided into 2 groups depending by meeting any of the following conditions prior to RDN: (1) >10 mmHg of office SBP reduction after aldosterone inhibition, (2) aldosterone-renin ratio >30 or (3) slow flow on the renal angiogram. RDN responders were defined by a reduction in 24-hour mean ≥6 mmHg or by ≥1 class of antihypertensive drug withdraw. RESULTS: A total of 46 patients were enrolled, of which 27 (59%) were in control group A and 19 (41%) in group B. The baseline age, gender, office and 24-hour SBP (mean 140.0 ± 12.8 mmHg vs. 144.0 ± 16.5 mmHg, p = 0.577) were comparable, while the number of prescribed drug classes was fewer in group A (4.0 ± 1.3 vs. 4.9 ± 0.9, p = 0.014). The proportion patients with prescribed aldosterone antagonist or high aldosterone-renin ratios were higher in group B. At 12 months post RDN, the results were significantly better in group B in terms of mean change in office SBP (12.4 ± 23.5 mmHg vs. 29.9 ± 25.5 mmHg, p = 0.046) and the proportion of RDN responders (51.9% vs. 89.5%, p < 0.001). CONCLUSION: RDN was more effective in patients with any of 3 clinical indices.

The autonomic balance of heart rhythm complexity after renal artery denervation: insight from entropy of entropy and average entropy analysis.

BACKGROUND: The current method to evaluate the autonomic balance after renal denervation (RDN) relies on heart rate variability (HRV). However, parameters of HRV were not always predictive of response to RDN. Therefore, the complexity and disorder of heart rhythm, measured by entropy of entropy (EoE) and average entropy (AE), have been used to analyze autonomic dysfunction. This study evaluated the dynamic changes in autonomic status after RDN via EoE and AE analysis. METHODS: Five patients were prospectively enrolled in the Global SYMPLICITY Registry from 2020 to 2021. 24-h Holter and ambulatory blood pressure monitoring (ABPM) was performed at baseline and 3 months after RDN procedures. The autonomic status was analyzed using the entropy-based AE and EoE analysis and the conventional HRV-based low frequency (LF), high frequency (HF), and LF/HF. RESULTS: After RDN, the ABPM of all patients showed a significant reduction in blood pressure (BP) and heart rate. Only AE and HF values of all patients had consistent changes after RDN (p < 0.05). The spearman rank-order correlation coefficient of AE vs. HF was 0.86, but AE had a lower coefficient of variation than HF. CONCLUSIONS: Monitoring the AE and EoE analysis could be an alternative to interpreting autonomic status. In addition, a relative change of autonomic tone, especially an increasing parasympathetic activity, could restore autonomic balance after RDN.

A collaborative study to establish the national standard for SARS-CoV-2 RNA nucleic acid amplification techniques (NAAT) in Taiwan.

The conventional PCR remains a valuable method to detect the newly emergent coronavirus rapidly and accurately. Our investigation aimed to establish the standard materials of SARS-CoV-2 for NAAT detection. We provided formalin-inactivated SARS-CoV-2 and confirmed RNA copy numbers. In addition, the virus genome was confirmed with whole-genome sequencing and identified as Wuhan/WI04/2019. Seven laboratories were invited for this collaborative study, according to the reporting data, we determined the SARS-CoV-2 with the unit of 6.35 Log10 copies/mL as the national standard. The availability of the national standard (NS) of SARS-CoV-2 will facilitate the standardization and harmonization of SARS-CoV-2 NAAT assays.

Effects of lorcaserin on cardiometabolic risk factors in overweight and obese patients: A systematic review and meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Lorcaserin is a selective serotonin 2c receptor agonist approved as an anti-obesity agent. The additional cardiometabolic benefits associated with lorcaserin have not been conclusively established. The aim of the systematic review and meta-analysis is to examine the effects of lorcaserin on blood pressure, heart rate and other metabolic parameters in overweight and obese patients from randomized controlled clinical trials (RCTs). METHODS: A literature search was conducted on PubMed, EMBASE and Cochrane Central using the search terms 'lorcaserin' and 'randomized controlled trials' without language restrictions. RCTs with a follow-up period of at least 24 weeks were included in the meta-analysis. RESULTS AND DISCUSSION: Six studies with 9452 patients in the lorcaserin group and 9392 patients in the placebo group were included. Compared with placebo, lorcaserin not only reduced weight, BMI and waist circumference but also improved SBP, DBP, heart rate, LDL, triglycerides, fasting plasma glucose and HbA1c. Our findings suggest that lorcaserin has trivial though consistent and favourable effects on blood pressure, heart rate and metabolic syndrome. WHAT IS NEW AND CONCLUSION: Lorcaserin improved all cardiometabolic parameters modestly in addition to its weight loss effect in overweight and obese patients. More research is needed to determine its long-term cardiovascular benefits.

The Use and Clinical Outcomes of Single-Burr Rotational Atherectomy: The Experience of a Local Hospital in Taiwan.

BACKGROUND: Treating heavily calcified lesions is a challenge and is associated with high re-stenosis and target lesion revascularization (TLR). Before stent implantation, lesions must be adequately prepared using rotational atherectomy (RA), which has shown favorable results. The study aims to report our hospital's clinical outcomes when using rotational atherectomy on complex and heavily calcified coronary lesions with a single-burr strategy. METHODS: We retrospectively analyzed 58 patients who underwent percutaneous coronary interventions with RA at our center between December 2006 and April 2017. Data on immediate post-procedural events and major adverse cardiovascular events were collected during follow-up, including cardiovascular death, myocardial infarction, TLR, target vessel revascularization (TVR) and stroke. RESULTS: Of the 58 patients and 90 lesions treated over 10 years, 88 lesions (97.8%) used only one burr. The intervention procedure success rate was 100%. During a mean follow-up of 41.2 months, 6 patients experienced acute coronary syndrome, 12 required TLR, 2 needed TVR, and 6 died due to a cardiovascular event. We divided lesions into 5 categories. The prevalence of lesions and the burr size most commonly used were: category 1 (ostial lesion, 8.9%, 1.75 mm), category 2 (focal lesion, 20%, 1.75 mm), category 3 (intermediate lesion, 13.3%, 1.5 mm), category 4a (long, looser lesion, 26.7%, 1.5 mm), and category 4b (long, rigid lesion, 31.1%, 1.25 mm). CONCLUSIONS: Rather than a routine step-by-step strategy for RA, this study shows convincing evidence supporting the use of this device to treat complex calcified coronary lesions using a single-burr strategy.

Relations between baseline burden, maximum duration, and relative reduction of atrial fibrillation: Insights from continuous monitoring in rhythm control.

INTRODUCTION: Cardiac implantable electronic devices (CIEDs) can measure atrial fibrillation (AF) early; however, the timing for administering antiarrhythmic drugs (AADs) to suppress AF remains unclear. This study aimed to investigate the association between baseline values and changes after AAD in terms of relative reduction of AF burden (RRAB) and maximum AF duration (RRMD). METHODS: This multicenter retrospective study screened all patients with nonpermanent AF who had dual-chamber pacemakers and only enrolled those receiving a naive AAD between September 2009 and December 2014. AF burden and maximum duration were calculated using CIED at 0 and 3 to 6 months after starting rhythm control. All the enrolled patients were divided into four groups according to baseline AF burden. RRAB and RRMD were monitored using CIEDs. RESULTS: Overall, 145 eligible subjects received a naive AAD for nonpermanent AF. The mean RRAB in the four groups (AF burden <1%, 1%-4%, 4%-18%, and ≥18%) were -65.3%, -46.4%, -34.7%, and -27.9% (P = 0.005), respectively. Mean RRMD were -26.8%, -12.4%, 4.2%, and 6.0%, respectively ( P = 0.006). Multivariate analysis revealed that the lowest baseline AF burden (<1%) was significantly associated with greater RRAB, which was not observed in the RRMD model. CONCLUSIONS: Lower baseline AF burden was associated with greater RRAB by AADs. Our finding suggests that rhythm control should be started in the early stage to achieve better responses to AADs.

Effect of Radiofrequency-Based Renal Denervation: The Impact of Unplanned Medication Change from a Systematic Review and Meta-Analysis.

BACKGROUND: Catheter-based renal denervation (RDN) has emerged as a promising treatment option for hypertension. However, randomized controlled trials (RCTs) have reported conflicting results on blood pressure (BP) reduction. Patient- and procedure-related confounders have been implied as the potential sources of inconsistent BP responses. We aimed to investigated whether unplanned and frequent medication changes in RDN studies affected the BP response to RDN by conducting sensitivity and subgroup analyses, according to antihypertensive medication change rates in a meta-analysis of RCTs. METHODS: We searched the PUBMED, EMBASE, and COCHRANE databases up to May 2018. RCTs that studied the effects of RDN on hypertensive patients were included. A meta-analysis was carried out using RevMan 5.3. RESULTS: A total of 12 studies were included, of which four fulfilled the inclusion criteria of < 10% medication change rate in our review. Subgroup meta-analyses of the four RCTs with < 10% medication change rates showed statistically significant reductions of 6.07 mmHg and 7.12 mmHg in 24-hour and office systolic BP, respectively. The 24-hour and office diastolic BP were also reduced (mean difference = -3.89 mmHg and -4.27 mmHg, respectively). These subgroup analyses had no heterogeneity (I2 = 0%). In contrast, the pooled analysis of the 12 studies and the subgroup analysis of eight studies with > 10% medication change rates both had a high level of heterogeneity and no significant BP reduction. CONCLUSIONS: The effectiveness of RDN was demonstrated across a broad range of antihypertensive medications used at baseline after removing the confounder of unplanned medication changes.

Effectiveness of a Non-Taped Compression Dress in Patients Receiving Cardiac Implantable Electronic Devices.

BACKGROUND: Hematoma and skin damage are not uncommon after cardiac implantable electronic device (CIED) placement. The use of conventional hemostatic gauze and tape seems to be suboptimal in controlling these complications. This study aimed to evaluate the impact of a novel compression dress with a special pad and elastic bands for postoperative care. METHODS: A total of 175 CIED recipients were randomly divided into two groups: an experimental group with 85 patients who used a non-taped compression dress and a control group with 90 patients who used conventional gauze ball and elastic tapes. Skin integrity, hematoma, and oozing were compared between these two groups within 7 days after surgery. RESULTS: The mean age of the patients was 71.2 ± 13.3 years, and 83 (47.4%) were male. The results of the experimental vs. control group were as follows: skin integrity - 96.5% vs. 86.7% (p < 0.05); hematoma - 0% vs. 7.8% (p < 0.05); and oozing - 1.2% vs. 7.8% (p < 0.05). All observed endpoints were better in the experimental group. CONCLUSIONS: The use of a non-taped compression dress was associated with less unfavorable outcomes in terms of skin integrity and hemostasis.

MicroRNA-184 Deregulated by the MicroRNA-21 Promotes Tumor Malignancy and Poor Outcomes in Non-small Cell Lung Cancer via Targeting CDC25A and c-Myc.

BACKGROUND: MicroRNA (miR)-184 has been reported to have a dual role in human cancers. However, the role of miR-184 in non-small cell lung cancer (NSCLC) remains unclear. METHODS: Wild-type or mutant CDC25A promoters were constructed by PCR and site-directed mutagenesis to verify whether miR-184 could inhibit CDC25A expression at post-transcription level. Boyden chamber assay was used to assess whether miR-184 could modulate cell invasiveness via targeting CDC25A and c-Myc. We utilized 124 tumors from NSCLC patients to determine miR-184, miR-21, PDCD4 mRNA, c-Myc mRNA, and CDC25A mRNA expression levels by means of real-time PCR analysis. The prognostic value of CDC25A, c-Myc, and miR-184 on overall survival (OS) and relapse-free survival (RFS) was evaluated by Kaplan-Meier and Cox regression analysis. RESULTS: MiR-184 suppressed CDC25A expression by enhancing the instability of its mRNA as a result of miR-184 binding to its coding region. An increase in CDC25A expression by means of a reduction in miR-184 promotes cell invasiveness. Moreover, a concomitant increase in CDC25A and c-Myc expression as a result of decreased miR-184 via the miR-21-mediated PDCD4 reduction is responsible for cell invasiveness. Among patients, miR-184 expression in lung tumors was found to correlate negatively with CDC25A mRNA, c-Myc mRNA, and miR-21 expression, but was positively related to PDCD4 mRNA expression. High-miR-184, High-CDC25A, or high-c-Myc mRNA tumors exhibited shorter OS and RFS periods than their counterparts. The worst OS and RFS were observed in low-miR-184/high-CDC25A/high-c-Myc tumors, followed by low-miR-184 /high-CDC25A, low-miR-184/high-c-Myc, high-c-Myc, and high-CDC25A tumors. CONCLUSIONS: MiR-184 as a tumor suppressor miR inhibits cell proliferation and invasion capability via targeting CDC25A and c-Myc. Low miR-184 level may predict worse prognosis in NSCLC patients.

MicroRNA-21 promotes tumour malignancy via increased nuclear translocation of ß-catenin and predicts poor outcome in APC-mutated but not in APC-wild-type colorectal cancer.

MiR-21 has been associated with poor prognosis in colon adenocarcinomas. However, in our preliminary data, the prognostic value of miR-21 levels was observed only in adenomatous polyposis coli (APC)-mutated tumours, not in APC-wild-type tumours. We explored whether ß-catenin nuclear translocation was synergistically promoted by miR-21 in APC-mutated cells but not in APC-wild-type cells. We enrolled 165 colorectal tumour to determine APC mutation, miR-21 levels and nuclear ß-catenin expression by direct sequencing, real-time PCR and immunohistochemistry. Overall survival and relapse-free survival were analysed by Kaplan-Meier and Cox regression models. The mechanistic action of ß-catenin nuclear translocation modulated by miR-21 and its effect on cell invasion were evaluated in a cell model. Positive nuclear ß-catenin expression was more commonly occurred in APC-mutated tumours than in APC-wild-type tumours. High miR-21 levels were relatively more common in tumours with positive nuclear ß-catenin expression than in those with negative nuclear ß-catenin expression. APC-mutated tumours with high miR-21 levels had shorter overall survival and relapse-free survival periods compared with others. However, the prognostic value of miR-21 levels was not observed in APC-wild-type tumours. Phosphorylation of ß-catenin at Ser552 via the miR-21-mediated PTEN/AKT axis plays a critical role in ß-catenin nuclear translocation in APC-mutated cells but not in APC-wild-type cells. Moreover, nuclear ß-catenin expression increased by miR-21 is responsible for the capability of invasiveness. In summary, nuclear translocation of ß-catenin increased by miR-21 promotes tumour malignancy and a poor outcome in APC-mutated patients but not in APC-wild-type colorectal cancer.

Cardiovascular outcomes associated with SGLT2 inhibitor therapy in patients with type 2 diabetes mellitus and cancer: a systematic review and meta-analysis.

BACKGROUND: Cancer patients with diabetes are at increased risk for cardiovascular diseases due to common risk factors and well-documented drug-associated cardiotoxicity. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have shown cardiovascular benefits in patients with diabetes, but their effects on cancer patients remain unclear. This study aimed to evaluate the cardiovascular outcomes associated with SGLT2 inhibitor therapy in patients with concomitant diabetes and cancer. METHODS: We conducted a systematic review and meta-analysis of cohort studies comparing cardiovascular outcomes between cancer patients with diabetes receiving SGLT2 inhibitors and those not receiving SGLT2 inhibitors. PubMed, Embase, and the Cochrane Library were searched from inception to February 29, 2024. The primary outcome was all-cause mortality, and the secondary outcomes were heart failure hospitalization, and adverse events. Random-effect models were used to calculate pooled risk ratios (RR) with 95% confidence intervals (CI). Subgroup and sensitivity analyses were conducted to identify potential sources of heterogeneity and explore the effect of SGLT2 inhibitors on mitigating cardiotoxicity. RESULTS: Nine cohort studies involving 82,654 patients were included. SGLT2 inhibitor use was associated with a significantly lower risk of all-cause mortality (RR 0.46, 95% CI 0.31-0.68, P < 0.0001; I2 = 98%) and heart failure hospitalization (RR 0.49, 95% CI 0.30-0.81, P = 0.006; I2 = 21%) compared to non-use. The mortality benefit remained significant in patients receiving anthracycline chemotherapy (RR 0.50, 95% CI 0.28-0.89, P = 0.02; I2 = 71%). SGLT2 inhibitor use was also associated with a lower risk of sepsis (RR 0.32, 95% CI 0.23-0.44, P < 0.00001; I2 = 0%) and no increased risk of diabetic ketoacidosis (RR 0.66, 95% CI 0.20-2.16, P = 0.49; I2 = 0%). CONCLUSIONS: SGLT2 inhibitor therapy is associated with lower risks of all-cause mortality and heart failure hospitalization in patients with concomitant diabetes and cancer. These findings suggest that SGLT2 inhibitors may offer cardiovascular benefits in this high-risk population. Randomized controlled trials are needed to validate these findings and evaluate the safety and efficacy of SGLT2 inhibitors in specific cancer types and treatment regimens.

Reduced-Dose Rivaroxaban Is Associated with Lower All-Cause Mortality in Older Patients with Nonvalvular Atrial Fibrillation.

BACKGROUND: Reduced-dose rivaroxaban (10 mg) was used in the J-ROCKET AF trial, demonstrating safety in the Asian population. It remains unclear whether treatment with reduced-dose versus full-dose rivaroxaban (20 mg/15 mg) is associated with all-cause mortality in older patients with nonvalvular atrial fibrillation. Proposed: To evaluate the effects of reduced-dose rivaroxaban on all-cause mortality in patients over 85. METHODS: We retrospectively enrolled medical records representing the period from October 2012 to November 2016. The 2 × 2 factorial design incorporated age (≥85 vs. <85) and rivaroxaban use (reduced vs. full dose). The primary study outcomes were all-cause and cardiac-related mortality. RESULTS: The study enrolled 2386 patients with a mean age of 76.6 ± 10.4 years; 51.8% were male. In the ≥85 group (n = 593), the reduced-dose subgroup had lower all-cause (5.3% vs. 10.6%, p = 0.02) and cardiac-related mortality (1.9% vs. 5.1%, p = 0.04), whereas the younger patients receiving reduced-dose rivaroxaban had higher all-cause mortality (3.7% vs. 1.8%, p = 0.01) but no difference in cardiac-related mortality (1.2% vs. 0.7%, p = 0.33). The rate of hospitalization for heart failure was significantly lower in the elderly group with reduced-dose rivaroxaban (7.2% vs. 15.7%, p < 0.01) but not in the younger group. After adjusting for confounders in the older group, treatment with reduced-dose rivaroxaban was associated with lower risk of all-cause mortality (adjusted HR (aHR): 0.40, 95% CI: 0.21-0.74, p < 0.01) and hospitalization for heart failure (aHR: 0.54, 95% CI: 0.29-0.99, p = 0.05). No associations were found between rivaroxaban dose and cardiac-related mortality in either group, nor between younger age and any outcome. CONCLUSIONS: Reduced-dose rivaroxaban was associated with lower risks of all-cause mortality and hospitalization for heart failure in older patients with nonvalvular atrial fibrillation. Future studies can investigate the effect of reduced-dose rivaroxaban on prognoses in elderly individuals ≥85 years in the west.

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.

Risks and outcomes of critical limb ischemia in hemodialysis patients: a prospective cohort study.

Background: Peripheral arterial disease (PAD) is more common in patients receiving maintenance hemodialysis than in the general population. Critical limb ischemia (CLI), the most severe form of PAD, is associated with high amputation and mortality risk. However, few prospective studies are available evaluating this disease's presentation, risk factors and outcomes for patients receiving hemodialysis. Methods: The Hsinchu VA study, a prospective multicentre study, investigated the impact of clinical factors on cardiovascular outcomes of patients receiving maintenance hemodialysis from January 2008 until December 2021. We evaluated the presentations and outcomes of patients with newly diagnosed PAD and the correlations of clinical variables with newly diagnosed CLI. Results: Of 1136 study participants, 1038 had no PAD on enrolment. After a median follow-up period of 3.3 years, 128 had newly diagnosed PAD. Of these, 65 presented with CLI, and 25 underwent amputation or died from PAD. Patients presenting with CLI had more below-the-knee (52%) and multi-level (41%) disease, and completely occluded segments (41%), and higher risk for amputation or PAD-related death compared with patients without CLI (27.7% vs 9.5%, P = .01). After multivariate adjustment, disability, diabetes mellitus, current smoking and atrial fibrillation were significantly associated with newly diagnosed CLI. Conclusions: Patients undergoing hemodialysis had higher rates of newly diagnosed CLI than the general population. Those with disabilities, diabetes mellitus, smoking and atrial fibrillation may require careful examination for PAD. Trial registration: Hsinchu VA study, ClinicalTrials.gov identifier: NCT04692636.

Iron deficiency in Taiwanese patients with heart failure and reduced ejection fraction.

BACKGROUND: Iron deficiency (ID) is a common comorbidity among patients with heart failure and reduced ejection fraction (HFrEF), and is associated with poorer outcomes independent of anemia. This study aimed to evaluate the prevalence and prognostic significance of ID in Taiwanese patients with HFrEF. METHODS: We included HFrEF patients from two multicenter cohorts at different periods. The multivariate Cox regression analysis was applied to assess the risk of outcomes associated with ID, accounting for the varying risk of death. RESULTS: Of the 3612 patients with HFrEF registered from 2013 to 2018, 665 patients (18.4%) had available baseline iron profile measurements. Of these, 290 patients (43.6%) were iron deficient; 20.2% had ID+/anemia+, 23.4% ID+/anemia-, 21.5% ID-/anemia+, and 34.9% ID-/anemia-. Regardless of anemia status, patients with coexisting ID had a higher risk than those without ID (all-cause mortality: 14.3 vs 9.5 per 100 patient-years, adjusted hazard ratio [HR] 1.33; 95% confidence interval [CI], 0.96-1.85; p = 0.091; cardiovascular mortality: 10.5 per 100 patient-years vs 6.1, adjusted HR 1.54 [95% CI, 1.03-2.30; p = 0.037]; cardiovascular mortality or first unplanned hospitalization for HF: 36.7 vs 19.7 per 100 patient-years, adjusted HR 1.57 [95% CI, 1.22-2.01; p < 0.001]). Among patients eligible for treatment in the IRONMAN trial design (43.9%), parenteral iron therapy was estimated to reduce heart failure hospitalizations and cardiovascular deaths by 13.7 per 100 patient-years. CONCLUSION: Iron profiles were tested in less than one-fifth of the Taiwanese HFrEF cohort. ID was present in 43.6% of tested patients and was independently associated with poor prognosis in these patients.