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.

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.

Erratum to: Common and differential effects of docosahexaenoic acid and eicosapentaenoic acid on helper T-cell responses and associated pathways.

[Erratum to: BMB Reports 2021; 54(5): 278-283, PMID: 33972011] In the originally published version of this article, there was an error in the Supplementary information. Fig. 1 as following image was missing in the Supplementary Information. The Supplementary file in the original version has now been updated to include the corrected. We apologize for any inconvenience that this may have caused.

Characteristics, Outcomes, and Treatment of Heart Failure With Improved Ejection Fraction.

Background Many patients with heart failure ( HF ) with reduced ejection fraction ( HF r EF ) experience improvement or recovery of left ventricular ejection fraction ( LVEF ). Data on clinical characteristics, outcomes, and medical therapy in patients with HF with improved ejection fraction (HFiEF) are scarce. Methods and Results Of 5625 consecutive patients hospitalized for acute HF in the KorAHF (Registry [Prospective Cohort] for Heart Failure in Korea) study, 5103 patients had baseline echocardiography and 2302 patients had follow-up echocardiography at 12 months. HF phenotypes were defined as persistent HF r EF ( LVEF ≤40% at baseline and at 1-year follow-up), HF i EF ( LVEF ≤40% at baseline and improved up to 40% at 1-year follow-up), HF with midrange ejection fraction (LVEF between 40% and <50%), and HF with preserved ejection fraction ( LVEF ≥50%). The primary outcome was 4-year all-cause mortality from the time of HF i EF diagnosis. Among 1509 HF r EF patients who had echocardiography 1 year after index hospitalization, 720 (31.3%) were diagnosed as having HF i EF . Younger age, female sex, de novo HF , hypertension, atrial fibrillation, and ß-blocker use were positive predictors and diabetes mellitus and ischemic heart disease were negative predictors of HF i EF . During 4-year follow-up, patients with HF i EF showed lower mortality than those with persistent HF r EF in univariate, multivariate, and propensity-score-matched analyses. ß-Blockers, but not renin-angiotensin system inhibitors or mineralocorticoid receptor antagonists, were associated with a reduced all-cause mortality risk (hazard ratio: 0.59; 95% CI , 0.40-0.87; P=0.007). Benefits for outcome seemed similar among patients receiving low- or high-dose ß-blockers (log-rank, P=0.304). Conclusions HF i EF is a distinct HF phenotype with better clinical outcomes than other phenotypes. The use of ß-blockers may be beneficial for these patients. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifier: NCT01389843.

Repositioning of the antipsychotic trifluoperazine: Synthesis, biological evaluation and in silico study of trifluoperazine analogs as anti-glioblastoma agents.

Repositioning of the antipsychotic drug trifluoperazine for treatment of glioblastoma, an aggressive brain tumor, has been previously suggested. However, trifluoperazine did not increase the survival time in mice models of glioblastoma. In attempt to identify an effective trifluoperazine analog, fourteen compounds have been synthesized and biologically in vitro and in vivo assessed. Using MTT assay, compounds 3dc and 3dd elicited 4-5 times more potent inhibitory activity than trifluoperazine with IC50 = 2.3 and 2.2 µM against U87MG glioblastoma cells, as well as, IC50 = 2.2 and 2.1 µM against GBL28 human glioblastoma patient derived primary cells, respectively. Furthermore, they have shown a reasonable selectivity for glioblastoma cells over NSC normal neural cell. In vivo evaluation of analog 3dc confirmed its advantageous effect on reduction of tumor size and increasing the survival time in brain xenograft mouse model of glioblastoma. Molecular modeling simulation provided a reasonable explanation for the observed variation in the capability of the synthesized analogs to increase the intracellular Ca2+ levels. In summary, this study presents compound 3dc as a proposed new tool for the adjuvant chemotherapy of glioblastoma.

Vitamin D supplements reduce depressive symptoms and cardiac events in heart failure patients with moderate to severe depressive symptoms.

BACKGROUND: Depressive symptoms and vitamin D deficiency predict cardiac events in heart failure patients, but whether vitamin D supplements are associated with depressive symptoms and cardiac events in heart failure patients remains unknown. PURPOSE: The purpose of this study was to compare the association of vitamin D supplement use with depressive symptoms and cardiac events in heart failure patients with mild or moderate to severe depressive symptoms. METHODS: A total of 177 heart failure patients with depressive symptoms (Patient Health Questionnaire-9 score ≥5) completed a three-day food diary to determine dietary vitamin D deficiency. Patients were split into four groups by dietary vitamin D adequacy versus deficiency and vitamin D supplement use versus non-use. The Patient Health Questionnaire-9 was used to reassess depressive symptoms at six months. Data on cardiac events for up to one year and vitamin D supplement use were obtained from patient interview and medical record review. Hierarchical linear and Cox regressions were used for data analysis. RESULTS: Sixty-six patients (37.3%) had dietary vitamin D deficiency and 80 (45.2%) used vitamin D supplements. In patients with moderate to severe depressive symptoms, the group with dietary vitamin D deficiency and no supplements had the highest Patient Health Questionnaire-9 score at six months (ß=0.542, p<0.001) and shortest cardiac event-free survival ( p<0.001) among the four groups, the group with dietary vitamin D deficiency and no supplements didn't have the highest Patient Health Questionnaire-9 score at six months and shortest cardiac event-free survival in patients with mild depressive symptoms. CONCLUSIONS: Vitamin D supplements predicted lower depressive symptoms and reduced cardiac events for patients with moderate to severe depressive symptoms. Vitamin D deficiency was associated with higher risk of shorter cardiac event-free survival in heart failure patients regardless of vitamin D supplementation.

The Relationship of Depressive Symptoms and Vitamin D Intake to Cardiac Event-Free Survival in Patients With Heart Failure.

BACKGROUND: Low vitamin D and depressive symptoms are associated with inflammation activation that predicts cardiovascular disease. Little is known about the relationships among vitamin D intake, depressive symptoms, and cardiac events in heart failure (HF). PURPOSE: The aim of this study is to determine the relationships among vitamin D deficiency, depressive symptoms, and cardiac events. METHODS: A total of 204 HF patients completed a 3-day food diary to determine average daily intake of vitamin D. Patients completed the Patient Health Questionnaire-9 to assess somatic and cognitive depressive symptoms and were split into 2 groups using the Patient Health Questionnaire-9 cut-point score of 10 (< 10, no depressive symptoms; ≥ 10, depressive symptoms). Data on cardiac events during 1 year were obtained through medical record review. Hierarchical Cox and logistic regressions were used for data analyses. RESULTS: Sixty patients (29.4%) had depressive symptoms and 106 (52.0%) had vitamin D deficiency. Depressive symptoms (hazard ratio [HR], 1.93; P = .031) and vitamin D deficiency (HR, 1.84, P = .036) predicted shorter cardiac event-free survival in Cox regression. Depressive symptoms predicted shorter cardiac event-free survival in patients with vitamin D deficiency (HR, 2.16; P = .038), but not those with vitamin D adequacy. Somatic depressive symptoms were associated with vitamin D deficiency (odds ratio, 1.12; P = .028) in logistic regression, whereas cognitive depressive symptoms were not. CONCLUSIONS: Vitamin D deficiency and depressive symptoms predicted shorter cardiac event-free survival. Depressive symptoms did not predict cardiac events in HF patients with vitamin D adequacy. Somatic depressive symptoms predicted vitamin D deficiency, but cognitive depressive symptoms did not. Additional research is necessary to determine the protective role of vitamin D in the link between somatic depressive symptoms and cardiac events.

Micronutrient Deficiency Independently Predicts Adverse Health Outcomes in Patients With Heart Failure.

BACKGROUND: Despite growing evidence on the important role of micronutrients in prognosis of heart failure (HF), there has been limited research that micronutrient deficiency predicts health outcomes in patients with HF. PURPOSE: The aim of this study was to determine whether micronutrient deficiency independently predicts adverse health outcomes. METHODS: A total of 113 consecutive outpatients with HF completed a 3-day food diary to measure intake of 15 micronutrients. The Computer Aided Nutrition Analysis Program for Professionals was used to analyze the food diaries and determine dietary micronutrient deficiencies. Patients completed the Minnesota Living With HF Questionnaire to assess health-related quality of life (HRQoL) and were followed up for 1 year to determine cardiac-related hospitalization or cardiac death. Hierarchical multiple linear regressions and Cox proportional hazard regressions were used to determine whether micronutrient deficiencies predicted health outcomes. RESULTS: Fifty-eight patients (51%) had at least 3 micronutrient deficiencies (range, 0-14). Calcium, magnesium, and vitamin D were the most common micronutrient deficiencies. Micronutrient deficiency was independently associated with worse HRQoL (ß = .187, P = .025) in hierarchical multiple linear regression. Thirty-nine patients were hospitalized or died during 1-year follow-up because of cardiac problems. The number of micronutrient deficiencies independently predicted cardiac event-free survival (hazard ratio, 1.14; 95% confidence interval, 1.02-1.28). CONCLUSIONS: These findings show that micronutrient deficiency independently predicted poor HRQoL and earlier cardiac event-free survival in patients with HF. Further research is needed to provide for specific dietary guidelines for better health outcomes in HF patients.

Effect of high-dose statin loading on biomarkers related to inflammation and renal injury in patients hospitalized with acute heart failure. Randomized, controlled, open-label, prospective pilot study.

BACKGROUND: High-dose statin loading is known to reduce periprocedural myocardial infarction and contrast-induced acute kidney injury in patients undergoing percutaneous coronary intervention. However, the clinical role of high-dose statin loading in patients with acute heart failure (AHF) remains unknown. METHODS AND RESULTS: In a prospective, single-center, randomized, controlled, open-label pilot study, patients hospitalized with AHF were randomly assigned to receive oral high-dose atorvastatin loading (80 mg for 3 days, followed by 10 mg/day until discharge) or no statin therapy, on top of optimal HF treatment. The primary outcome measures were changes to the level of biomarkers related to inflammation and renal injury from admission to hospital day 4. No significant changes in the levels of NT-proBNP (-2,627±4,956 vs. -2,981±6,951 pg/ml, P=0.845), hsCRP (-6.1±16.4 vs. -2.1±16.2 mg/L, P=0.105), cystatin C (0.002±0.185 vs. 0.009±0.216 mg/L, P=0.904), ACR (-886.3±1,984.9 vs. -165.6±825.2 mg/day, P=0.124) were observed in either group. In-hospital mortality (4.3% vs. 3.8%, P>0.999) and all-cause mortality at 90 days (4.3% vs. 3.8%, P>0.999) were not significantly different between groups. CONCLUSIONS: This pilot study showed that oral high-dose atorvastatin loading may be used safely in patients with AHF, but is not effective in reducing the levels of circulating biomarkers related to inflammation and renal injury during hospitalization.