The effect of sustained-release CARvedilol in patients with hypErtension and heart failure with preserved ejection fraction: a study protocol for a pilot randomized controlled trial (CARE-preserved HF).

Background: Although beta-blockers improve clinical outcomes in heart failure with reduced ejection fraction, the benefit of beta-blockers in heart failure with preserved ejection fraction (HFpEF) is uncertain. Global longitudinal strain (GLS) is a robust predictor of heart failure outcomes, and recent studies have shown that beta-blockers are associated with improved survival in those with low GLS (GLS <14%) but not in those with GLS ≥14% among patients with LVEF ≥40%. Therefore, the objective of this trial is to evaluate the effect of sustained-release carvedilol (carvedilol-SR) on the outcome [N-terminal pro-B-natriuretic peptide (NT-proBNP) concentration] in patients with hypertension and HFpEF and will assess the differential effects of these drugs on the outcome, according to the GLS categories. Methods: This prospective randomized double-blind multicenter trial (CARE-preserved HF) will include 100 patients with HFpEF from three tertiary hospitals in South Korea. Patients with HFpEF and hypertension aged ≥20 years who have evidence of functional and structural heart disease on echocardiography and elevated natriuretic peptide will be enrolled. Eligible participants will be randomized 1:1 to either the carvedilol-SR group (n = 50) or the placebo group (n = 50). Patients in the carvedilol-SR group will receive 8, 16, 32, or 64 mg carvedilol-SR once daily for 6 months, and the dose of carvedilol will be up-titrated at the discretion of the treating physicians. The primary efficacy outcome was the time-averaged proportional change in N-terminal pro-B-natriuretic peptide concentration from baseline to months 3 and 6. We will also evaluate the differential effects of carvedilol-SR on primary outcomes according to GLS, using a cut-off of 14% or the median value. Discussion: This randomized controlled trial will investigate the efficacy and safety of carvedilol-SR in patients with HFpEF and hypertension. Clinical Trial Registration: ClinicalTrial.gov, identifier NCT05553314.

The Third Nationwide Korean Heart Failure III Registry (KorHF III): The Study Design Paper.

With advancements in both pharmacologic and non-pharmacologic treatments, significant changes have occurred in heart failure (HF) management. The previous Korean HF registries, namely the Korea Heart Failure Registry (KorHF-registry) and Korean Acute Heart Failure Registry (KorAHF-registry), no longer accurately reflect contemporary acute heart failure (AHF) patients. Our objective is to assess contemporary AHF patients through a nationwide registry encompassing various aspects, such as clinical characteristics, management approaches, hospital course, and long-term outcomes of individuals hospitalized for AHF in Korea. This prospective observational multicenter cohort study (KorHF III) is organized by the Korean Society of Heart Failure. We aim to prospectively enroll 7,000 or more patients hospitalized for AHF at 47 tertiary hospitals in Korea starting from March 2018. Eligible patients exhibit signs and symptoms of HF and demonstrate either lung congestion or objective evidence of structural or functional cardiac abnormalities in echocardiography, or isolated right-sided HF. Patients will be followed up for up to 5 years after enrollment in the registry to evaluate long-term clinical outcomes. KorHF III represents the nationwide AHF registry that will elucidate the clinical characteristics, management strategies, and outcomes of contemporary AHF patients in Korea. Trial Registration: ClinicalTrials.gov Identifier: NCT04329234.

Effectiveness of a Smartphone App-Based Intervention With Bluetooth-Connected Monitoring Devices and a Feedback System in Heart Failure (SMART-HF Trial): Randomized Controlled Trial.

BACKGROUND: Current heart failure (HF) guidelines recommend a multidisciplinary approach, discharge education, and self-management for HF. However, the recommendations are challenging to implement in real-world clinical settings. OBJECTIVE: We developed a mobile health (mHealth) platform for HF self-care to evaluate whether a smartphone app-based intervention with Bluetooth-connected monitoring devices and a feedback system can help improve HF symptoms. METHODS: In this prospective, randomized, multicenter study, we enrolled patients 20 years of age and older, hospitalized for acute HF, and who could use a smartphone from 7 tertiary hospitals in South Korea. In the intervention group (n=39), the apps were automatically paired with Bluetooth-connected monitoring devices. The patients could enter information on vital signs, HF symptoms, diet, medications, and exercise regimen into the app daily and receive feedback or alerts on their input. In the control group (n=38), patients could only enter their blood pressure, heart rate, and weight using conventional, non-Bluetooth devices and could not receive any feedback or alerts from the app. The primary end point was the change in dyspnea symptom scores from baseline to 4 weeks, assessed using a questionnaire. RESULTS: At 4 weeks, the change in dyspnea symptom score from baseline was significantly greater in the intervention group than in the control group (mean -1.3, SD 2.1 vs mean -0.3, SD 2.3; P=.048). A significant reduction was found in body water composition from baseline to the final measurement in the intervention group (baseline level mean 7.4, SD 2.5 vs final level mean 6.6, SD 2.5; P=.003). App adherence, which was assessed based on log-in or the percentage of days when symptoms were first observed, was higher in the intervention group than in the control group. Composite end points, including death, rehospitalization, and urgent HF visits, were not significantly different between the 2 groups. CONCLUSIONS: The mobile-based health platform with Bluetooth-connected monitoring devices and a feedback system demonstrated improvement in dyspnea symptoms in patients with HF. This study provides evidence and rationale for implementing mobile app-based self-care strategies and feedback for patients with HF. TRIAL REGISTRATION: ClinicalTrials.gov NCT05668000; https://clinicaltrials.gov/study/NCT05668000.

Eligibility and Cost-Utility Analysis of Dapagliflozin in Patients with Heart Failure Across the Whole Spectrum of Ejection Fraction in South Korea.

BACKGROUND: The DAPA-HF and DELIVER trials demonstrated the clinical benefits of dapagliflozin in heart failure (HF) patients across the entire ejection fraction (EF) spectrum. However, further investigation is needed for the real-world application of dapagliflozin in HF patients. This study examines the proportion of real-world HF patients eligible for dapagliflozin and evaluates the cost-effectiveness of adding dapagliflozin to current HF therapy. METHODS: Data from the nationwide prospective registry, the Korean Acute Heart Failure (KorAHF) registry, were used to determine dapagliflozin eligibility based on the enrollment criteria of the DAPA-HF/DELIVER trials. A cost-utility analysis was conducted using a Markov model to assess the cost-effectiveness of dapagliflozin by comparing it to the standard of care. RESULTS: Out of 5178 KorAHF patients, 48.7% met the enrollment criteria of the DAPA-HF/DELIVER trials, while 89.5% met the label criteria (US Food and Drug Administration, European Medicines Agency, and Korean Ministry of Food and Drug Safety). Eligibility was highest among HF patients with preserved EF (55.3% vs. HF with mildly reduced EF and HF with reduced EF 46.4%). Dapagliflozin proved to be cost-effective, with an incremental cost-effectiveness ratio (ICER) of 4557 US dollar (US$) per quality-adjusted life year, which falls below the US$18,182 willingness-to-pay threshold. The cost-effectiveness benefit was more pronounced in patients with a left ventricular EF (LVEF) ≤ 40% (ICER US$3279 for LVEF ≤ 40% vs. US$8383 for LVEF > 40%). CONCLUSIONS: Discrepancies in dapagliflozin eligibility were observed between real-world data and clinical trial results. The addition of dapagliflozin to HF therapy proved to be highly cost-effective across the entire EF spectrum.

Real-World Eligibility and Cost-Effectiveness Analysis of Empagliflozin for Heart Failure in Korea.

BACKGROUND: The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) approved empagliflozin for reducing cardiovascular mortality and heart failure (HF) hospitalization in patients with both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). However, limited data are available on the generalizability of empagliflozin to clinical practice. Therefore, we evaluated real-world eligibility and potential cost-effectiveness based on a nationwide prospective HF registry. METHODS: A total of 3,108 HFrEF and 2,070 HFpEF patients from the Korean Acute Heart Failure (KorAHF) registry were analyzed. Eligibility was estimated by inclusion and exclusion criteria of EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced) and EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction (EMPEROR-Preserved) trials and by FDA & EMA label criteria. The cost-utility analysis was done using a Markov model to project the lifetime medical cost and quality-adjusted life year (QALY). RESULTS: Among the KorAHF patients, 91.4% met FDA & EMA label criteria, while 44.7% met the clinical trial criteria. The incremental cost-effectiveness ratio of empagliflozin was calculated at US$6,764 per QALY in the overall population, which is far below a threshold of US$18,182 per QALY. The cost-effectiveness benefit was more evident in patients with HFrEF (US$5,012 per QALY) than HFpEF (US$8,971 per QALY). CONCLUSION: There is a large discrepancy in real-world eligibility for empagliflozin between FDA & EMA labels and clinical trial criteria. Empagliflozin is cost-effective in HF patients regardless of ejection fraction in South Korea health care setting. The efficacy and safety of empagliflozin in real-world HF patients should be further investigated for a broader range of clinical applications. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01389843.

Metformin treatment is associated with improved survival in diabetic patients hospitalized with acute heart failure: A prospective observational study using the Korean acute heart failure registry data.

AIMS: Although the hypothesis that metformin is beneficial for patients with diabetes and heart failure (HF) has been steadily raised, there is limited data on metformin use in patients with acute HF. We analyzed the association of metformin on all-cause mortality in hospitalized patients with type 2 diabetes and acute HF. METHODS: The Korean Acute Heart Failure registry prospectively enrolled patients hospitalized for acute HF from 2011 to 2014. Among this cohort, we analyzed patients with diabetes with baseline estimated glomerular filtration rate (eGFR) of 30 ml/min/1.73 m2 or more. We analyzed the all-cause mortality and re-hospitalization for HF within 1 year after discharge. Inverse probability treatment weighting method was used to adjust baseline differences on metformin treatment. RESULTS: The study analyzed data from 1,309 patients with HF and diabetes (mean age 69 years, 56 % male). Among them, 613 (47 %) patients were on metformin at admission. During the median follow-up period of 11 months, 132 (19 %) and 74 (12 %) patients not receiving and receiving metformin treatment died, respectively. The mortality rate was lower in metformin users than in non-users (hazard ratio 0.616 [0.464-0.819] P<0.001). After adjustment, metformin was significantly associated with a lower risk for the mortality (hazard ratio 0.677 [0.495-0.928] P=0.015). In subgroup analyses, this association remains significant irrespective of baseline kidney function (eGFR <60 or ≥60 ml/min/1.73 m2, P-for-interaction=0.176) or left ventricular ejection fraction (<40 %, 40-49 %, or ≥50 %, P-for-interaction=0.224). CONCLUSIONS: Metformin treatment at the time of admission was associated with a lower risk for 1-year mortality in patients with diabetes, hospitalized for acute HF.

Korean Society of Heart Failure Guidelines for the Management of Heart Failure: Advanced and Acute Heart Failure.

The Korean Society of Heart Failure (KSHF) Guidelines provide evidence-based recommendations based on Korean and international data to guide adequate diagnosis and management of heart failure (HF). Since introduction of 2017 edition of the guidelines, management of advanced HF has considerably improved, especially with advances in mechanical circulatory support and devices. The current guidelines addressed these improvements. In addition, we have included recently updated evidence-based recommendations regarding acute HF in these guidelines. In summary, Part IV of the KSHF Guidelines covers the appropriate diagnosis and optimized management of advanced and acute HF.

Korean Society of Heart Failure Guidelines for the Management of Heart Failure: Management of the Underlying Etiologies and Comorbidities of Heart Failure.

Most patients with heart failure (HF) have multiple comorbidities, which impact their quality of life, aggravate HF, and increase mortality. Cardiovascular comorbidities include systemic and pulmonary hypertension, ischemic and valvular heart diseases, and atrial fibrillation. Non-cardiovascular comorbidities include diabetes mellitus (DM), chronic kidney and pulmonary diseases, iron deficiency and anemia, and sleep apnea. In patients with HF with hypertension and left ventricular hypertrophy, renin-angiotensin system inhibitors combined with calcium channel blockers and/or diuretics is an effective treatment regimen. Measurement of pulmonary vascular resistance via right heart catheterization is recommended for patients with HF considered suitable for implantation of mechanical circulatory support devices or as heart transplantation candidates. Coronary angiography remains the gold standard for the diagnosis and reperfusion in patients with HF and angina pectoris refractory to antianginal medications. In patients with HF and atrial fibrillation, long-term anticoagulants are recommended according to the CHA2DS2-VASc scores. Valvular heart diseases should be treated medically and/or surgically. In patients with HF and DM, metformin is relatively safer; thiazolidinediones cause fluid retention and should be avoided in patients with HF and dyspnea. In renal insufficiency, both volume status and cardiac performance are important for therapy guidance. In patients with HF and pulmonary disease, beta-blockers are underused, which may be related to increased mortality. In patients with HF and anemia, iron supplementation can help improve symptoms. In obstructive sleep apnea, continuous positive airway pressure therapy helps avoid severe nocturnal hypoxia. Appropriate management of comorbidities is important for improving clinical outcomes in patients with HF.

Efficacy and safety of standard dose triple combination of telmisartan 80 mg/amlodipine 5 mg/chlorthalidone 25 mg in primary hypertension: A randomized, double-blind, active-controlled, multicenter phase 3 trial.

The authors evaluated the efficacy, safety, and characteristics of patients who respond well to standard dose triple combination therapy including chlorthalidone 25 mg with telmisartan 80 mg plus amlodipine 5 mg in hypertensive patients. This is a multicenter, double-blind, active-controlled, phase 3, randomized trial. Patients are randomized to triple combination (telmisartan 40 mg/amlodipine 5 mg/chlorthalidone 12.5 mg, TEL/AML/CHTD group) or dual combination (telmisartan 40 mg/amlodipine 5 mg, TEL/AML group) treatment and then dose up titration to TEL 80/AML5/CHTD25mg and TEL80/AML5, respectively. The primary endpoint is the change of mean sitting systolic blood pressure (MSSBP) at week 8. A Target BP achievement rate, a response rate, and the safety endpoints are also evaluated. Total 374 patients (mean age = 60.9 ± 10.7 years, male = 78.3%) were randomized to the study. The baseline MSSBPs/diastolic BPs were 149.9 ± 12.2/88.5 ± 10.4 mm Hg. After 8 weeks treatment, the change of MSSBPs at week 8 are -19.1 ± 14.9 mm Hg (TEL/AML/CHTD) and -11.4 ± 14.7 mm Hg (TEL/AML) (p < .0001). The achievement rates of target BP (53.8% vs. 37.8%, p = .0017) and responder rate (54.8% vs. 35.6%, p = .0001) at week 8 were significantly higher in TEL/AML/CHTD. There are no serious adverse event and no one discontinued medication due to adverse event. Among the TEL 80/AML5/CHTD25mg treatment group, patients of female or age ≥ 65 years old showed higher rate of target BP achievement than relatively young male. (61.4 vs. 46.8%, p = .042) Our study showed standard dose triple combination of telmisartan 80 mg/amlodipine 5 mg/chlorthalidone 25 mg is efficacious and safe in treatment of primary hypertension. Target BP achievement with triple therapy would be facilitated in female or old age.

Korean Society of Heart Failure Guidelines for the Management of Heart Failure: Advanced and Acute Heart Failure.

The Korean Society of Heart Failure (KSHF) Guidelines provide evidence-based recommendations based on Korean and international data to guide adequate diagnosis and management of heart failure (HF). Since introduction of 2017 edition of the guidelines, management of advanced HF has considerably improved, especially with advances in mechanical circulatory support and devices. The current guidelines addressed these improvements. In addition, we have included recently updated evidence-based recommendations regarding acute HF in these guidelines. In summary, Part IV of the KSHF Guidelines covers the appropriate diagnosis and optimized management of advanced and acute HF.

Korean Society of Heart Failure Guidelines for the Management of Heart Failure: Management of the Underlying Etiologies and Comorbidities of Heart Failure.

Most patients with heart failure (HF) have multiple comorbidities, which impact their quality of life, aggravate HF, and increase mortality. Cardiovascular comorbidities include systemic and pulmonary hypertension, ischemic and valvular heart diseases, and atrial fibrillation. Non-cardiovascular comorbidities include diabetes mellitus (DM), chronic kidney and pulmonary diseases, iron deficiency and anemia, and sleep apnea. In patients with HF with hypertension and left ventricular hypertrophy, renin-angiotensin system inhibitors combined with calcium channel blockers and/or diuretics is an effective treatment regimen. Measurement of pulmonary vascular resistance via right heart catheterization is recommended for patients with HF considered suitable for implantation of mechanical circulatory support devices or as heart transplantation candidates. Coronary angiography remains the gold standard for the diagnosis and reperfusion in patients with HF and angina pectoris refractory to antianginal medications. In patients with HF and atrial fibrillation, long-term anticoagulants are recommended according to the CHA2DS2-VASc scores. Valvular heart diseases should be treated medically and/or surgically. In patients with HF and DM, metformin is relatively safer; thiazolidinediones cause fluid retention and should be avoided in patients with HF and dyspnea. In renal insufficiency, both volume status and cardiac performance are important for therapy guidance. In patients with HF and pulmonary disease, beta-blockers are underused, which may be related to increased mortality. In patients with HF and anemia, iron supplementation can help improve symptoms. In obstructive sleep apnea, continuous positive airway pressure therapy helps avoid severe nocturnal hypoxia. Appropriate management of comorbidities is important for improving clinical outcomes in patients with HF.

Iron Deficiency in Korean Patients With Heart Failure.

BACKGROUND: Although iron deficiency (ID) is an important and treatable risk factor for heart failure (HF), data on ID are scarce in Asian patients with HF. Therefore, we sought to determine the prevalence and clinical characteristics of ID in hospitalized Korean patients with HF. METHODS: In this prospective, multicenter cohort study, 461 patients with acute HF seen at five tertiary centers from January to November 2019 in Korea were enrolled. ID was defined as serum ferritin < 100 µg/L or ferritin 100-299 µg/L in combination with transferrin saturation < 20%. RESULTS: The patients' mean age was 67.6 ± 14.9 years, and 61.8% were male. Among total 461 patients, ID was present in 248 patients (53.8%). The prevalence of ID was significantly higher in women than in men (65.3% vs. 47.3%, P < 0.001). In a multivariable logistic regression analysis, the independent predictors of ID were female sex (odds ratio [OR], 2.19; 95% confidence interval [CI], 1.47-3.30), valvular heart disease (OR, 2.10; 95% CI, 1.10-4.17), higher heart rate (OR, 1.10; 95% CI, 1.01-1.21), anemia (OR, 1.60; 95% CI, 1.07-2.40), and the use of clopidogrel (OR, 1.56; 95% CI, 1.00-2.45). Among women, the prevalence of ID did not significantly differ between younger and older women (< 65 years: 73.7% vs. ≥ 65 years: 63.0%, P = 0.222), those with low and high body mass index (BMI < 25 kg/m²: 66.2% vs. BMI ≥ 25 kg/m²: 69.6%, P = 0.703), or those with low and high natriuretic peptide (NP) levels (NP < median: 69.8% vs. NP ≥ median: 61.1%, P = 0.295). Only 0.2% patients with acute HF received intravenous iron supplementation in Korea. CONCLUSION: The prevalence of ID is high in hospitalized Korean patients with HF. Because ID cannot be diagnosed by clinical parameters, routine laboratory examinations are necessary to identify patients with ID. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04812873.

The ReInforcement of adherence via self-monitoring app orchestrating biosignals and medication of RivaroXaban in patients with atrial fibrillation and co-morbidities: a study protocol for a randomized controlled trial (RIVOX-AF).

Background: Because of the short half-life of non-vitamin K antagonist oral anticoagulants (NOACs), consistent drug adherence is crucial to maintain the effect of anticoagulants for stroke prevention in atrial fibrillation (AF). Considering the low adherence to NOACs in practice, we developed a mobile health platform that provides an alert for drug intake, visual confirmation of drug administration, and a list of medication intake history. This study aims to evaluate whether this smartphone app-based intervention will increase drug adherence compared with usual care in patients with AF requiring NOACs in a large population. Methods: This prospective, randomized, open-label, multicenter trial (RIVOX-AF study) will include a total of 1,042 patients (521 patients in the intervention group and 521 patients in the control group) from 13 tertiary hospitals in South Korea. Patients with AF aged ≥19 years with one or more comorbidities, including heart failure, myocardial infarction, stable angina, hypertension, or diabetes mellitus, will be included in this study. Participants will be randomly assigned to either the intervention group (MEDI-app) or the conventional treatment group in a 1:1 ratio using a web-based randomization service. The intervention group will use a smartphone app that includes an alarm for drug intake, visual confirmation of drug administration through a camera check, and presentation of a list of medication intake history. The primary endpoint is adherence to rivaroxaban by pill count measurements at 12 and 24 weeks. The key secondary endpoints are clinical composite endpoints, including systemic embolic events, stroke, major bleeding requiring transfusion or hospitalization, or death during the 24 weeks of follow-up. Discussion: This randomized controlled trial will investigate the feasibility and efficacy of smartphone apps and mobile health platforms in improving adherence to NOACs. Trial registration: The study design has been registered in ClinicalTrial.gov (NCT05557123).

Korean Society of Heart Failure Guidelines for the Management of Heart Failure: Definition and Diagnosis.

The Korean Society of Heart Failure guidelines aim to provide physicians with evidence-based recommendations for diagnosing and managing patients with heart failure (HF). In Korea, the prevalence of HF has been rapidly increasing in the last 10 years. HF has recently been classified into HF with reduced ejection fraction (EF), HF with mildly reduced EF, and HF with preserved EF (HFpEF). Moreover, the availability of newer therapeutic agents has led to an increased emphasis on the appropriate diagnosis of HFpEF. Accordingly, this part of the guidelines will mainly cover the definition, epidemiology, and diagnosis of HF.

Korean Society of Heart Failure Guidelines for the Management of Heart Failure: Treatment.

The Korean Society of Heart Failure (KSHF) guidelines aim to provide physicians with evidence-based recommendations for the management of patients with heart failure (HF). After the first introduction of the KSHF guidelines in 2016, newer therapies for HF with reduced ejection fraction, HF with mildly reduced ejection fraction, and HF with preserved ejection fraction have since emerged. The current version has been updated based on international guidelines and research data on Korean patients with HF. Herein, we present Part II of these guidelines, which comprises treatment strategies to improve the outcomes of patients with HF.

Treatment Strategies of Improving Quality of Care in Patients With Heart Failure.

Heart failure (HF) is a global health problem closely related to morbidity and mortality. As the burden of HF increases, it is necessary to manage and treat this condition well. However, there are differences between real-world practice and guidelines for the optimal treatment for HF. Patient-related, healthcare provider-related, and health system-related factors contribute to poor adherence to optimal care. This review article aims to examine HF treatment patterns and treatment adherence in real-world practice, identify clinical gaps to suggest ways to improve the quality of care for HF and clinical outcomes for patients with HF. Although it is important to optimize treatment based on evidence-based guidelines to the greatest extent, it is known that there is still poor treatment adherence, and many patients do not receive guideline-directed medical therapy, especially at the early stages. To improve medication adherence, qualitative evaluation through performance measurement, as well as education of patients, caregivers and medical staff through a multidisciplinary approach are important.

Korean Society of Heart Failure Guidelines for the Management of Heart Failure: Definition and Diagnosis.

The Korean Society of Heart Failure guidelines aim to provide physicians with evidence-based recommendations for diagnosing and managing patients with heart failure (HF). In Korea, the prevalence of HF has been rapidly increasing in the last 10 years. HF has recently been classified into HF with reduced ejection fraction (HFrEF), HF with mildly reduced ejection fraction (EF), and HF with preserved EF (HFpEF). Moreover, the availability of newer therapeutic agents has led to an increased emphasis on the appropriate diagnosis of HFpEF. Accordingly, this part of the guidelines will mainly cover the definition, epidemiology, and diagnosis of HF.

Korean Society of Heart Failure Guidelines for the Management of Heart Failure: Treatment.

The Korean Society of Heart Failure (KSHF) guidelines aim to provide physicians with evidence-based recommendations for the management of patients with heart failure (HF). After the first introduction of the KSHF guidelines in 2016, newer therapies for HF with reduced ejection fraction, HF with mildly reduced ejection fraction, and HF with preserved ejection fraction have since emerged. The current version has been updated based on international guidelines and research data on Korean patients with HF. Herein, we present Part II of these guidelines, which comprises treatment strategies to improve the outcomes of patients with HF.

Impact of the ultra-long 48 mm drug-eluting stent on procedural and clinical outcomes in patients with diffuse long coronary artery disease.

BACKGROUND: Diffuse coronary artery disease (CAD) is a prognostic factor after percutaneous coronary intervention (PCI) and requires multiple overlapping stent implantations. HYPOTHESIS: We investigated the impact of ultra-long 48 mm drug-eluting stent (DES) on procedural and clinical outcomes in real-world practice. METHODS: Patients who underwent DES implantation for a lesion length of >40 mm were selected from a prospective registry between 2019 and 2021. Patients treated with one or more ultra-long 48 mm DES were in the ultra-long DES group (n = 221). The others comprised the conventional DES group (n = 428). Procedural and clinical outcomes were compared after propensity score matching (PSM). The primary endpoint was a device-oriented composite outcome (DOCO) consisting of cardiac death, target vessel-related myocardial infarction, and target lesion revascularization at 1-year follow-up. RESULTS: After PSM, 158 matched pairs of patients showed no differences in the baseline clinical and angiographic characteristics. The stent delivery failure rate, the use of guide-extension catheter or anchor balloon technique, and the procedural success rate were similar for both groups. Approximately two-thirds of lesions could be treated with one DES in the ultra-long DES group. At 1-year follow-up, the DOCO was similar for both groups (2.5% vs. 0.6%, p = .168). CONCLUSIONS: In daily clinical practice, ultra-long DES implantation is as safe and effective as multiple overlapping conventional DES implants in treating diffuse long CAD. However, ultra-long DES can reduce the number of stents. (Trial Registration: ClinicalTrials.gov Identifier: NCT02038127).

Clinical Characteristics and Outcome of Immediate-Release Versus SLOW-Release Carvedilol in Heart Failure Patient (SLOW-HF): a Prospective Randomized, Open-Label, Multicenter Study.

PURPOSE: Carvedilol demonstrated therapeutic benefits in patients with heart failure and reduced ejection fraction (HFrEF). However, it had a short half-life time mandating twice a day administration. We investigated whether slow-release carvedilol (carvedilol-SR) is non-inferior to standard immediate-release carvedilol (carvedilol-IR) in terms of clinical efficacy in patients with HFrEF. METHODS: We randomly assigned patients with HFrEF to receive carvedilol-SR once a day or carvedilol-IR twice a day. The primary endpoint was the change in N-terminal pro B-natriuretic peptide (NT-proBNP) level from baseline to 6 months after randomization. The secondary outcomes were proportion of patients with NT-proBNP increment > 10% from baseline, mortality rate, readmission rate, changes in blood pressure, quality of life, and drug compliance. RESULTS: A total of 272 patients were randomized and treated (median follow-up time, 173 days). In each group of patients taking carvedilol-SR and those taking carvedilol-IR, clinical characteristics were well balanced. No patient died during follow-up, and there was no significant difference in the change of NT-proBNP level between two groups (-107.4 [-440.2-70.3] pg/mL vs. -91.2 [-504.1-37.4] pg/mL, p = 0.101). Change of systolic and diastolic blood pressure, control rate and response rate of blood pressure, readmission rate, and drug compliance rate were also similar. For safety outcomes, the occurrence of adverse reactions did not differ between carvedilol-SR group and carvedilol-IR group. CONCLUSION: Carvedilol-SR once a day was non-inferior to carvedilol-IR twice a day in patients with HFrEF. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03209180 (registration date: July 6, 2017).