Left atrial reservoir longitudinal strain and its incremental value to the left ventricular global longitudinal strain in predicting anthracycline-induced cardiotoxicity.

BACKGROUND: Left ventricular global longitudinal strain (LVGLS) has been recommended by current guidelines for diagnosing anthracycline-induced cardiotoxicity. However, little is known about the early changes in left atrial (LA) morphology and function in this population. Our study aimed to evaluate the potential usefulness of LA indices and their incremental value to LVGLS with three-dimensional echocardiography (3DE) in the early detection of subclinical cardiotoxicity in patients with lymphoma receiving anthracycline. METHODS: A total of 80 patients with diffuse large B-cell lymphoma who received six cycles of anthracycline-based treatment were enrolled. Echocardiography was performed at baseline (T0), after four cycles (T1), and after the completion of six cycles of chemotherapy (T2). Left ventricular ejection fraction (LVEF), LVGLS, LA volumes, LA emptying fraction (LAEF), LA active emptying fraction (LAAEF), and LA reservoir longitudinal strain (LASr) were quantified with 3DE. Left atrioventricular global longitudinal strain (LAVGLS) was calculated as the sum of peak LASr and the absolute value of peak LVGLS (LAVGLS = LASr+|LVGLS|). LV cardiotoxicity was defined as a new LVEF reduction by ≥10 percentage points to an LVEF of ≤50%. RESULTS: Fourteen (17.5%) patients developed LV cardiotoxicity at T2. LA volumes, LAEF, and LAAEF remained stable over time. Impairment of LASr (28.35 ± 5.03 vs. 25.04 ± 4.10, p < .001), LVGLS (-22.77 ± 2.45 vs. -20.44 ± 2.62, p < .001), and LAVGLS (51.12 ± 5.63 vs. 45.61 ± 5.22, p < .001) was observed by the end of the fourth cycle of chemotherapy (T1). Statistically significant declines in LVEF (61.30 ± 4.73 vs. 57.08 ± 5.83, p < .001) were only observed at T2. The relative decrease in LASr (ΔLASr), LVGLS (ΔLVGLS), and LAVGLS (ΔLAVGLS) from T0 to T1 were predictors of LV cardiotoxicity. A ΔLASr of >19.75% (sensitivity, 71.4%; specificity, 87.9%; area under the curve (AUC), .842; p < .001), a ΔLVGLS of >13.19% (sensitivity, 78.6%; specificity, 74.2%; AUC, .763; p < .001), and a ΔLAVGLS of >16.80% (sensitivity, 78.6%; specificity, 93.9%; AUC, .905; p < .001) predicted subsequent LV cardiotoxicity at T2, with the AUC of ΔLAVGLS significantly larger than that of ΔLVGLS (.905 vs. .763, p = .027). Compared to ΔLVGLS, ΔLAVGLS showed improved specificity (93.9% vs. 74.2%, p = .002) and maintained sensitivity in predicting LV cardiotoxicity. CONCLUSIONS: LASr could predict anthracycline-induced LV cardiotoxicity with excellent diagnostic performance. Incorporating LASr into LVGLS (LAVGLS) led to a significantly improved specificity and maintained sensitivity in predicting LV cardiotoxicity.

Short Registry of Terminal Forms of Chronic Heart Failure in the Samara Region.

AIM: To study the clinical characteristics and prognosis of patients with functional class (FC) III-IV chronic heart failure (CHF) who meet the criteria for inclusion in the palliative care program. MATERIAL AND METHODS: A short registry of severe CHF forms was conducted at 60 outpatient and inpatient clinics in the Samara region for one month (16.05.2022-15.06.2022). The registry included patients with FC III-IV CHF who sought medical help during that period. Lethal outcomes were assessed at 90 days after the inclusion in the registry using the Mortality Information and Analytics system. RESULTS: 591 patients (median age, 71.0 [64.0; 80.0] years were enrolled, including 339 (57.4%) men, of which 149 (24.1%) were of working age (under 65 years). The main cause of CHF was ischemic heart disease (64.5%). 229 (38.7%) patients had left ventricular ejection fraction <40%. During the past year, 513 (86.8%) patients had at least one hospitalization for decompensated CHF. 45.7% of patients had hydrothorax, and 11.3% of patients had ascites. Low systolic blood pressure was observed in more than 25% of patients; 14.2% required in-hospital inotropic support; and 9.1% received it on the outpatient basis. 4.2% of patients received outpatient oxygen support and 0.8% required the administration of narcotic analgesics. 12 (1.9%) patients were on the waiting list for heart transplantation. In this study, there was an inconsistency in the number of patients with ventricular tachycardia and/or left bundle branch block (LBBB) who were implanted with cardiac resynchronization therapy devices (CRTD) or an implantable cardioverter defibrillator (ICD), a total of 19 patients (11 patients with CRTD and 8 patients with ICD), while 58 (9.8%) patients had indications for CRTD/ICD implantation. Within 90 days from inclusion in the registry, 59 (10.0%) patients died. According to binary logistic regression analysis, the presence of LBBB, hydrothorax, the requirement for outpatient oxygen support, and a history of cardiac surgery were associated with a high risk of death. CONCLUSION: Patients with severe forms of CHF require not only adequate drug therapy, but also dynamic clinical observation supplemented with palliative care aimed at improving the quality of life, including the ethical principles of shared decision-making and advance care planning to identify the priorities and goals of patients in relation to their care.

Chronic Heart Failure in Patients Hospitalized in 2002 and 2021: Comparative Analysis of Prevalence, Clinical Course and Drug Therapy.

AIM: Comparative analysis of the prevalence of chronic heart failure (CHF), clinical and medical history data, and drug therapy of patients admitted to a cardiology hospital in 2002 and 2021. MATERIAL AND METHODS: The study analyzed the medical records of patients with a confirmed diagnosis of CHF who were admitted in 2002 (n=210) and 2021 (n=381) to a specialized cardiology hospital. RESULTS: According to medical records of 2021, the proportion of patients with a confirmed diagnosis of CHF (87.6%) in the cohort of patients admitted to a cardiology hospital was twice as high as in 2002 (46.4%; p<0.001). The majority of patients with CHF in the study sample were patients with preserved left ventricular ejection fraction (HFpEF). The proportion of such patients significantly increased to reach 75.9% in 2021 compared to 58.6% in 2002 (p<0.001). At the same time, the number of severe forms of CHF (NYHA functional class (FC) IV) decreased by 10% and was 13.2% in 2002 and 1.3% in 2021 (p<0.001). In the majority of patients, ischemic heart disease (98.1 and 91.1% in 2002 and 2021, respectively, p<0.001) and hypertension (80.5 and 98.2%, respectively, p<0.001) were diagnosed as the cause for CHF. Furthermore, the incidence of comorbidity increased significantly: atrial fibrillation was detected in 12.3% of patients in 2002 and 26.4% in 2021 (p < 0.001); type 2 diabetes mellitus, in 14.3 and 32% of patients (p <0.001); and obesity, in 33.3 and 43.7% of patients, respectively (p=0.018). The frequency of using the major groups of drugs increased during the analyzed period: renin-angiotensin-aldosterone system blockers were administered to 71.9% of patients in 2002 and to 87.7% in 2021 (p<0.001); beta-blockers were administered to 53.3 and 82.4% of patients (p<0.001); and mineralocorticoid receptor antagonists, to 1.9 and 18.6% of patients, respectively (p=0.004). CONCLUSION: In 2021, the proportion of patients with a confirmed diagnosis of CHF in the patient cohort admitted to a cardiology hospital was twice as high as in 2002; the phenotype with preserved left ventricular ejection fraction predominated in the CHF structure. During the analyzed twenty-year period, the prevalence of comorbidities increased among CHF patients. The prescription frequency of pathogenetic evidence-based therapy has significantly increased by 2021, however, it remains insufficient even in patients with CHF with reduced left ventricular ejection fraction.

Effect of an exercise-based cardiac rehabilitation program on quality of life of patients with chronic Chagas cardiomyopathy: results from the PEACH randomized clinical trial.

To investigate the effect of an exercise-based cardiac rehabilitation program on the quality of life (QoL) of patients with chronic Chagas cardiomyopathy (CCC). PEACH study was a single-center, superiority randomized clinical trial of exercise training versus no exercise (control). The sample comprised Chagas disease patients with CCC, left ventricular ejection fraction < 45%, without or with HF symptoms (CCC stages B2 or C, respectively). QoL was assessed at baseline, after three months, and at the end of six months of follow-up using the SF-36 questionnaire. Patients randomized for the exercise group (n = 15) performed exercise training (aerobic, strength and stretching exercises) for 60 min, three times a week, during six months. Patients in the control group (n = 15) were not provided with a formal exercise prescription. Both groups received identical nutritional and pharmaceutical counseling during the study. Longitudinal analysis of the effects of exercise training on QoL, considering the interaction term (group × time) to estimate the rate of changes between groups in the outcomes (represented as beta coefficient), was performed using linear mixed models. Models were fitted adjusting for each respective baseline QoL value. There were significant improvements in physical functioning (ß = + 10.7; p = 0.02), role limitations due to physical problems (ß = + 25.0; p = 0.01), and social functioning (ß = + 19.2; p < 0.01) scales during the first three months in the exercise compared to the control group. No significant differences were observed between groups after six months. Exercise-based cardiac rehabilitation provided short-term improvements in the physical and mental aspects of QoL of patients with CCC.Trial registration: ClinicalTrials.gov Identifier: NCT02517632; August 7, 2015.

Contemporary 1-Year Outcomes of Mitral Valve-in-Ring With Balloon-Expandable Aortic Transcatheter Valves in the U.S.

BACKGROUND: Adequate valve performance after surgical mitral valve repair with an annuloplasty ring is not always sustained over time. The risk of repeat mitral valve surgery may be high in these patients. Transcatheter mitral valve-in-ring (MViR) is emerging as an alternative for high-risk patients. OBJECTIVES: The authors sought to assess contemporary outcomes of MViR using third-generation balloon-expandable aortic transcatheter heart valves. METHODS: Patients who underwent MViR and were enrolled in the STDS/ACC TVT (Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy) Registry between August 2015 and December 2022 were analyzed. RESULTS: A total of 820 patients underwent MViR at 236 sites, mean age was 72.2 ± 10.4 years, 50.9% were female, mean STS score was 8.2% ± 6.9%, and most (78%) were in NYHA functional class III to IV. Mean left ventricular ejection fraction was 47.8% ± 14.2%, mean mitral gradient was 8.9 ± 7.0 mm Hg, and 75.5% had ≥ moderate mitral regurgitation. Access was transseptal in 93.9% with 88% technical success. All-cause mortality at 30 days was 8.3%, and at 1 year, 22.4%, with a reintervention rate of 9.1%. At 1-year follow-up, 75.6% were NYHA functional class I to II, Kansas City Cardiomyopathy Questionnaire score increased by 25.9 ± 29.1 points, mean mitral valve gradient was 8.4 ± 3.4 mm Hg, and 91.7% had ≤ mild mitral regurgitation. CONCLUSIONS: MViR with third-generation balloon-expandable aortic transcatheter heart valves is associated with a significant reduction in mitral regurgitation and improvement in symptoms at 1 year, but with elevated valvular gradients and a high reintervention rate. MViR is a reasonable alternative for high-risk patients unable undergo surgery who have appropriate anatomy for the procedure. (STS/ACC TVT Registry Mitral Module [TMVR]; NCT02245763).

Water Conservation Overrides Osmotic Diuresis During SGLT2 Inhibition in Patients With Heart Failure.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors are believed to improve cardiac outcomes due to their osmotic diuretic potential. OBJECTIVES: The goal of this study was to test the hypothesis that vasopressin-driven urine concentration overrides the osmotic diuretic effect of glucosuria induced by dapagliflozin treatment. METHODS: DAPA-Shuttle1 (Hepato-renal Regulation of Water Conservation in Heart Failure Patients With SGLT-2 Inhibitor Treatment) was a single-center, double-blind, randomized, placebo-controlled trial, in which patients with chronic heart failure NYHA functional classes I/II and reduced ejection fraction were randomly assigned to receive dapagliflozin 10 mg daily or placebo (1:1) for 4 weeks. The primary endpoint was change from baseline in urine osmolyte concentration. Secondary endpoints included changes in copeptin levels and solute free water clearance. RESULTS: Thirty-three randomized, sodium-glucose cotransporter 2 inhibitor-naïve participants completed the study, 29 of whom (placebo: n = 14; dapagliflozin: n = 15) provided accurate 24-hour urine collections (mean age 59 ± 14 years; left ventricular ejection fraction 31% ± 9%). Dapagliflozin treatment led to an isolated increase in urine glucose excretion by 3.3 mmol/kg/d (95% CI: 2.51-4.04; P < 0.0001) within 48 hours (early) which persisted after 4 weeks (late; 2.7 mmol/kg/d [95% CI: 1.98-3.51]; P < 0.0001). Dapagliflozin treatment increased serum copeptin early (5.5 pmol/L [95% CI: 0.45-10.5]; P < 0.05) and late (7.8 pmol/L [95% CI: 2.77-12.81]; P < 0.01), leading to proportional reductions in free water clearance (early: -9.1 mL/kg/d [95% CI: -14 to -4.12; P < 0.001]; late: -11.0 mL/kg/d [95% CI: -15.94 to -6.07; P < 0.0001]) and elevated urine concentrations (late: 134 mmol/L [95% CI: 39.28-229.12]; P < 0.01). Therefore, urine volume did not significantly increase with dapagliflozin (mean difference early: 2.8 mL/kg/d [95% CI: -1.97 to 7.48; P = 0.25]; mean difference late: 0.9 mL/kg/d [95% CI: -3.83 to 5.62]; P = 0.70). CONCLUSIONS: Physiological-adaptive water conservation eliminated the expected osmotic diuretic potential of dapagliflozin and thereby prevented a glucose-driven increase in urine volume of approximately 10 mL/kg/d · 75 kg = 750 mL/kg/d. (Hepato-renal Regulation of Water Conservation in Heart Failure Patients With SGLT-2 Inhibitor Treatment [DAPA-Shuttle1]; NCT04080518).

Factors influencing the therapeutic failure of high-flow nasal cannula oxygen humidification in patients with interstitial pneumonia complicated by respiratory failure.

OBJECTIVE: The aim of this study was to explore the factors influencing the treatment failure of high-flow nasal cannula (HFNC) therapy in patients with interstitial pneumonia (IP) complicated by respiratory failure. PATIENTS AND METHODS: A total of 158 patients with IP and respiratory failure treated with HFNC in our hospital from January 2020 to August 2023 were selected as the study population. Based on treatment efficacy, they were categorized into the HFNC treatment failure group and the HFNC treatment success group. Clinical data were compared between the two groups. Multiple logistic regression analysis was employed to identify independent factors influencing treatment failure, and the predictive value of these factors for HFNC treatment failure was assessed using receiver operating characteristic (ROC) curve analysis. RESULTS: After 7 days of HFNC treatment, among the 158 patients with IP and respiratory failure, 25 (15.8%) declared treatment failure, while the remaining 133 (84.2%) showed treatment success. Patients in the HFNC treatment failure group had significantly higher age, duration of IP, pre-treatment respiratory rate, C-reactive protein (CRP), and controlling nutritional status (CONUT) scores compared to the HFNC treatment success group. The PaO2/FiO2 ratio, left ventricular ejection fraction, and Glasgow Coma Scale (GCS) were significantly lower in the HFNC treatment failure group (p<0.05). Multiple logistic regression analysis revealed that pre-treatment PaO2/FiO2 ratio, CRP, CONUT, and GCS scores were independent factors influencing HFNC treatment failure in patients with IP and respiratory failure (p<0.05). Lower PaO2/FiO2 ratio and GCS scores, and higher CRP and CONUT scores were associated with an increased risk of HFNC treatment failure. ROC curve analysis indicated that pre-treatment PaO2/FiO2 ratio, CRP, CONUT, and GCS scores in patients with IP and respiratory failure had a high predictive value for HFNC treatment failure (p<0.05). CONCLUSIONS: The HFNC failure rate in patients with IP and respiratory failure is 15.8%. Pre-treatment PaO2/FiO2 ratio, CRP, CONUT, and GCS scores are independent factors associated with HFNC treatment failure and warrant clinical attention.

Study on the construction of nomogram prediction model for prognostic assessment of heart failure patients based on serological markers and echocardiography.

OBJECTIVE: We aimed to construct a nomogram prediction model for prognostic assessment of patients with heart failure (HF) based on serological markers and echocardiography. PATIENTS AND METHODS: A total of 200 HF patients admitted to the Second Affiliated Hospital of Nanchang University from January 2018 to January 2020 were selected as the research objects. According to the New York Heart Association (NYHA) cardiac function classification, they were divided into 3 groups, including 65 cases of grade II, 97 cases of grade III, and 38 cases of grade IV. Three groups of echocardiographic parameters were compared [including left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular end-systolic volume (LVESV)], differences in serum markers brain natriuretic peptide (BNP), soluble growth-stimulating expression gene 2 (sST2) and the Modified Early Warning Score (MEWS). The patients were divided into two groups according to their clinical outcomes during the follow-up period, including 52 cases in the death group and 148 cases in the survival group. The clinical data of the two groups were compared, and multi-factor logistic regression analysis was performed to screen out the independent risk factors affecting the patient's death. A nomogram model of the patient's mortality risk was constructed based on the independent risk factors. Receiver operating characteristic (ROC) curves and calibration curves were used to evaluate the discrimination and accuracy of the nomogram model. RESULTS: As the cardiac function class of elderly chronic heart failure (CHF) patients increases, LVEDD, LVESD, sST2, and MEWS increase and LVEF decreases (p<0.05). Multifactor analysis results showed that LVEF, LVEDD, sST2, and MEWS were independent factors affecting the clinical outcome of patients. The AUCs predicted using LVEF, LVEDD, sST2, and MEWS alone were 0.738, 0.775, 0.717, 0.831, and 0.768, respectively. There is a certain degree of discrimination, and the model has extremely high accuracy. CONCLUSIONS: MEWS, LVEDD, and sST2 increase as the NYHA cardiac function grade of HF patients increases and LVEF decreases, which can reflect the severity of the disease to a certain extent. Additionally, the nomogram model established based on this has a high predictive value for the long-term prognosis of patients and can formulate effective intervention measures for quantitative values.

Left Atrial Enlargement as a Predictor of Atrial Fibrillation in Rheumatic Mitral Valve Disease: An Echocardiography-based Retrospective Cross-sectional Study.

BACKGROUND: Rheumatic heart disease is a major cause of cardiovascular morbidity and mortality in developing nations and is a leading cause of hospital admission due to cardiac problems in our country. This study will evaluate the association between left atrial size and the occurrence of atrial fibrillation and describe the clinical characteristics along with complications related to Rheumatic Mitral valve disease. METHODS: A retrospective cross-sectional study was conducted at a tertiary care center from January 2018 to December 2019. Reports of 207 patients admitted to medical and/or surgical wards with echocardiographic diagnosis of rheumatic mitral valve disease with or without atrial fibrillation were reviewed. Data were collected, entered, and analyzed using the Statistical Package for the Social Science version 25.0. RESULTS: Among 207 patients, atrial fibrillation was present in 90 (43.5%) patients. Atrial fibrillation was higher in patients with mixed mitral valvular lesions compared to isolated mitral stenosis or mitral regurgitation. Univariate and multivariate analysis revealed left atrial size [aOR=1.067, 95% CI: 1.023 - 1.113, P= 0.002] and age [aOR = 1.073, 95% CI: 1.042 - 1.105, P<0.001] as an independent predictor of atrial fibrillation. CONCLUSIONS: Larger left atrium was an independent predictor of atrial fibrillation. Besides this, atrial fibrillation was associated with increasing age, mixed mitral valvular lesion, and moderately reduced left ventricular ejection fraction, but not associated with gender and mitral stenosis severity. Left atrial clot was significantly higher in patients with atrial fibrillation than in sinus rhythm.

Validation of TRI-SCORE for Outcome Prediction After Isolated Tricuspid Valve Surgery in Asian Patients.

BACKGROUND: TRI-SCORE was recently developed in Europe as a risk model for predicting in-hospital death after isolated tricuspid valve surgery. We aimed to validate TRI-SCORE in an Asian population and investigate its value for predicting long-term outcomes. METHODS AND RESULTS: The TRI-SCORE was calculated for 202 patients (65±11 years, 61% women, 81% functional tricuspid regurgitation) who underwent isolated tricuspid valve surgery for severe tricuspid regurgitation at 2 Korean centers and was based on 8 parameters: age, New York Heart Association class, right-sided heart failure signs, furosemide daily dose, glomerular filtration rate, bilirubin, left ventricular ejection fraction, and moderate/severe right ventricular dysfunction. The primary outcome was all-cause death during follow-up; the secondary outcome was in-hospital death. During a median follow-up duration of 50 (interquartile range, 21-82) months after isolated tricuspid valve surgery, 23 (11.4%) patients experienced the primary outcome, and 7 (3.5%) patients experienced the secondary outcome. Observed all-cause death and in-hospital death increased by up to 50% in those with higher scores. Patients with the primary outcome had a higher TRI-SCORE (4.5±2.4 versus 2.9±2.1; P=0.001) than those without. The TRI-SCORE showed a significant association with the primary outcome (concordance index, 0.77, cutoff value, 4) and in-hospital death (area under the curve, 0.84; cutoff value, 3). Using the Kaplan-Meier analysis, patients with a high TRI-SCORE exhibited a poor outcome for all-cause death at follow-up (log-rank P<0.001) and in-hospital death (log-rank P=0.004). CONCLUSIONS: TRI-SCORE was validated in an Asian population and helped predict long-term outcomes after isolated tricuspid valve surgery.

Impact of a Chronic Total Coronary Occlusion on the Incidence of Appropriate Implantable Cardioverter-Defibrillator Shocks and Mortality: A Substudy of the Dutch Outcome in ICD Therapy (DO-IT)) Registry.

BACKGROUND: Chronic total coronary occlusions (CTO) substantially increase the risk for sudden cardiac death. Among patients with chronic ischemic heart disease at risk for sudden cardiac death, an implantable cardioverter defibrillator (ICD) is the favored therapy for primary prevention of sudden cardiac death. This study sought to investigate the impact of CTOs on the risk for appropriate ICD shocks and mortality within a nationwide prospective cohort. METHODS AND RESULTS: This is a subanalysis of the nationwide Dutch-Outcome in ICD Therapy (DO-IT) registry of primary prevention ICD recipients in The Netherlands between September 2014 and June 2016 (n=1442). We identified patients with chronic ischemic heart disease (n=663) and assessed available coronary angiograms for CTO presence (n=415). Patients with revascularized CTOs were excluded (n=79). The primary end point was the composite of all-cause mortality and appropriate ICD shocks. Clinical follow-up was conducted for at least 2 years. A total of 336 patients were included, with an average age of 67±9 years, and 20.5% was female (n=69). An unrevascularized CTO was identified in 110 patients (32.7%). During a median follow-up period of 27 months (interquartile range, 24-32), the primary end point occurred in 21.1% of patients with CTO (n=23) compared with 11.9% in patients without CTO (n=27; P=0.034). Corrected for baseline characteristics including left ventricular ejection fraction, and the presence of a CTO was an independent predictor for the primary end point (hazard ratio, 1.82 [95% CI, 1.03-3.22]; P=0.038). CONCLUSIONS: Within this nationwide prospective registry of primary prevention ICD recipients, the presence of an unrevascularized CTO was an independent predictor for the composite outcome of all-cause mortality and appropriate ICD shocks.

Usefulness of Heart Failure Categories Based on Left Ventricular Ejection Fraction.

BACKGROUND: Heart failure guidelines have recently introduced a narrow category with mildly reduced left ventricular ejection fraction (LVEF) (heart failure with mildly reduced ejection fraction; LVEF 41%-49%) between the previous categories of reduced (heart failure with reduced ejection fraction; LVEF ≤40%) and preserved (heart failure with preserved ejection fraction; LVEF ≥50%) ejection fraction. Grouping of continuous measurements into narrow categories can be questioned if their variability is high. METHODS AND RESULTS: We constructed a cohort of all 9716 new cases of chronic heart failure with an available LVEF in Stockholm, Sweden, from January 1, 2015, until December 31, 2020. All values of LVEF were collected over time, and patients were followed up until death, moving out of Stockholm, or end of study. Mixed models were used to quantify within-person variance in LVEF, and multistate Markov models, with death as an absorbing state, to quantify the stability of LVEF categories. LVEF values followed a normal distribution. The SD of the within-person variance in LVEF over time was 7.4%. The mean time spent in any LVEF category before transition to another category was on average <1 year for heart failure with mildly reduced ejection fraction. Probabilities of transitioning between categories during the first year were substantial; patients with heart failure with mildly reduced ejection fraction had a probability of <25% of remaining in that category 1 year later. CONCLUSIONS: LVEF follows a normal distribution and has considerable variability over time, which may impose a risk for underuse of efficient treatment. The heart failure with mildly reduced ejection fraction category is especially inconstant. Assumptions of a patient's current LVEF should take this variability and the normal distribution of LVEF into account.

[Fuyu Decoction ameliorates myocardial fibrosis in rat model of heart failure by regulating Nrf2/GPX4-mediated ferroptosis].

This study aims to investigate the effect and mechanism of Fuyu Decoction(FYD) in the treatment of myocardial fibrosis in the rat model of heart failure(HF). Sixty Wistar rats were randomized into a modeling group(n=50) and a sham group(n=10). A post-myocardial infarction HF model was established by ligating the left anterior descending coronary artery in rats. The successfully modeled rats were assigned into model, low-dose(2.5 g·kg~(-1)) FYD(FYD-L), high-dose(5.0 g·kg~(-1)) FYD(FYD-H), and FYD+Nrf2 inhibitor(ML385, 30 mg·kg~(-1)) groups(n=10). FYD was administrated by gavage and ML385 by intraperitoneal injection. The rats in the sham and model groups were administrated with equal amounts of normal saline by gavage. After 8 weeks of intervention, the cardiac function indicators were measured, and the myocardial tissue morphology and collagen deposition were observed. The positive expression of collagens Ⅰ and Ⅲ, apoptosis, and oxidative stress were examined, and the levels of Fe~(2+) and reactive oxygen species(ROS) were determined. The protein levels of nuclear factor erythroid 2-related factor 2(Nrf2), solute carrier family 7 member 11(SLC7A11), glutathione peroxidase 4(GPX4), and acyl-coenzyme A synthase long chain family member 4(ACSL4) in the myocardial tissue were determined. Compared with sham group, the model group showed decreased left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS), increased left ventricular end internal dimension in systole(LVIDs), left ventricular internal diameter in diastole(LVIDd), and myocardial collagen deposition, positive expression of collagens Ⅰ and Ⅲ, elevated apoptosis rate and malondialdehyde(MDA), Fe~(2+), and ROS levels, lowered superoxide dismutase(SOD) and glutathione peroxidase(GSH) levels, down-regulated protein levels of Nrf2, SLC7A11, and GPX4, and up-regulated protein level of ACSL4. Compared with the model group, the above indicators were restored by FYD. Moreover, ML385 reversed the protective effect of FYD on myocardial fibrosis in HF rats. In conclusion, FYD can inhibit ferroptosis by activating the Nrf2/GPX4 pathway, thereby ameliorating myocardial fibrosis in HF rats.

Outcomes and predictors of left ventricle recovery in patients with severe left ventricular dysfunction undergoing transcatheter aortic valve implantation.

BACKGROUND: Data on the likelihood of left ventricle (LV) recovery in patients with severe LV dysfunction and severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI) and its prognostic value are limited. AIMS: We aimed to assess the likelihood of LV recovery following TAVI, examine its association with midterm mortality, and identify independent predictors of LV function. METHODS: In our multicentre registry of 17 TAVI centres in Western Europe and Israel, patients were stratified by baseline LV function (ejection fraction [EF] >/≤30%) and LV response: no LV recovery, LV recovery (EF increase ≥10%), and LV normalisation (EF ≥50% post-TAVI). RESULTS: Our analysis included 10,872 patients; baseline EF was ≤30% in 914 (8.4%) patients and >30% in 9,958 (91.6%) patients. The LV recovered in 544 (59.5%) patients, including 244 (26.7%) patients whose LV function normalised completely (EF >50%). Three-year mortality for patients without severe LV dysfunction at baseline was 29.4%. Compared to this, no LV recovery was associated with a significant increase in mortality (adjusted hazard ratio 1.32; p<0.001). Patients with similar LV function post-TAVI had similar rates of 3-year mortality, regardless of their baseline LV function. Three variables were associated with a higher likelihood of LV recovery following TAVI: no previous myocardial infarction (MI), estimated glomerular filtration rate >60 mL/min, and mean aortic valve gradient (mAVG) (expressed either as a continuous variable or as a binary variable using the standard low-flow, low-gradient aortic stenosis [AS] definition). CONCLUSIONS: LV recovery following TAVI and the extent of this recovery are major determinants of midterm mortality in patients with severe AS and severe LV dysfunction undergoing TAVI. Patients with no previous MI and those with an mAVG >40 mmHg show the best results following TAVI, which are at least equivalent to those for patients without severe LV dysfunction. (ClinicalTrials.gov: NCT04031274).

Activated rate-response is associated with increased mortality risk in cardiac device carriers with acute heart failure.

AIMS: This study investigated whether an activated R-mode in patients carrying a cardiac implantable electronic device (CIED) is associated with worse prognosis during and after an episode of acutely decompensated heart failure (AHF). METHODS: Six hundred and twenty-three patients participating in an ongoing prospective cohort study that phenotypes and follows patients admitted for AHF were studied. We compared CIED carriers with activated R-mode stimulation (CIED-R) to CIED carriers not in R-mode (CIED-0) and patients without CIEDs (no-CIED). The independent impact of R-mode activation on 12-month all-cause death was examined using uni- and multivariable Cox proportional hazards regression taking into account potential confounders, and hazard ratios (HR) with their 95% confidence intervals (CI) were reported. RESULTS: Mean heart rate on admission was lower in CIED-R (n = 37, 16% women) vs. CIED-0 (n = 64, 23% women) or no-CIED (n = 511, 43% women): 70 bpm vs. 80 bpm or 82 bpm; both p<0.001. In-hospital mortality was similar across groups, but age- and sex-adjusted all-cause 12-month mortality risk was differentially affected by R-mode activation; CIED-R vs. CIED-0: HR 2.44, 95%CI 1.25-4.74; CIED-R vs. no-CIED: HR 2.61, 95%CI 1.59-4.29. These effects persisted after multivariable adjustment for potential confounders. Within CIED-R, mortality risk was similar in patients with pacemakers vs. ICDs and in subgroups with left ventricular ejection fraction (LVEF) <50% vs. ≥50%. CONCLUSION: In patients admitted with AHF, R-mode stimulation was associated with a significantly increased 12-month mortality risk. Our findings shed new light on "admission heart rate" as a potentially treatable target in AHF. Our data are compatible with the concept that chronotropic incompetence contributes to an adverse outcome in these patients and may not be adequately treated through accelerometer-based R-mode stimulation.