Association between natriuretic peptides and C-reactive protein with frailty in heart failure: a systematic review and meta-analysis.

BackgroundHeart failure (HF) and frailty are accompanied by a bidirectional relationship, sharing common risk factors including elevated levels of natriuretic peptides and inflammation. The aim of this study was to compare biomarkers associated with poor clinical outcomes, that is, plasma brain natriuretic peptide (BNP), N-terminal-pro B-type natriuretic peptide (NT-proBNP), and C-reactive protein (CRP) in patients with HF and frailty vs. patients with HF without frailty.MethodsFrom inception until July 2023, PubMed, Scopus, Web of Science, and Cochrane Library a systematic literature search was conducted. To evaluate whether frailty is linked with greater levels of BNP, NT-proBNP, and CRP, a meta-analysis using a random-effects model was used to calculate the pooled effects (CRD42023446607).ResultsFifty-three studies were included in this systematic review and meta-analysis. Patients with HF and frailty displayed significantly higher levels of BNP (k = 11; SMD: 0.53, 95%CI 0.30-0.76, I2 = 86%, P 2 = 72%, P 2 = 62%, P ConclusionsFrailty in HF is linked to increased concentrations of BNP, NT-proBNP, and CRP, which have been epidemiologically associated with adverse outcomes. The increased risk of NYHA III/IV classification further emphasizes the clinical impact of frailty in this population

Association between the atrial tachyarrhythmia recurrence period and long-term major adverse clinical events following catheter ablation for atrial fibrillation

Background: We previously demonstrated the clinical events in patients who underwent catheter ablation (CA) for atrial fibrillation (AF). Data on the association between the period of atrial tachyarrhythmia (ATA) recurrence after CA and long-term major adverse clinical events (MACE) remain unclear. In this study, we evaluated this issue in patients with systolic impairment (left ventricular ejection fraction < 50%) and heart failure with preserved ejection fraction (HFpEF). Methods: We retrospectively collected data from 81 patients with systolic impairment and 83 patients with HFpEF who underwent CA for AF at our institution (median follow-up: 4.9 [3.6, 6.6] years). In each group, we compared the cumulative incidence of long-term MACE (since 1 year after CA) between patients with and without ATA recurrence at three follow-up periods (3, 6 months, and 1 year after index CA). We evaluated the period of recurrence, which was the most beneficial predictor of MACE among the periods. Results: In the systolic impairment group, the cumulative long-term MACE incidence was significantly higher in patients with ATA recurrence than in those without it within 6 months and 1 year (P = 0.04 and P = 0.01, respectively). Recurrence within 1 year showed the highest feasibility for predicting long-term MACE (area under the curve with 95% confidence interval [CI]:0.73 [0.61–0.84]). However, there was no difference in the incidence of MACE between patients with and without recurrence in a group with HFpEF in each period. Conclusion: ATA recurrence within 1 year could predict long-term MACE in patients with systolic impairment, but not in patients with HFpEF

Long‐term events following catheter‐ablation for atrial fibrillation in heart failure with preserved ejection fraction

Abstract Aims Data regarding prognostic events following catheter ablation (CA) for atrial fibrillation (AF) in patients with heart failure with preserved ejection fraction (HFpEF) are scarce. We conducted this study to compare the incidence of major adverse clinical events (MACE) following CA for AF between patients with HFpEF and those with systolic heart failure (HF). Methods and results This single‐centre observational study included 142 patients with HF who underwent CA for AF (median follow‐up: 4.0 [2.6, 6.3] years). The patients were grouped based on the presence of HFpEF (n = 84) and systolic HF (left ventricular ejection fraction <50%, n = 58). We compared the cumulative incidence and incidence rate of MACE, comprising all‐cause death, unplanned cardiovascular hospitalization (CVH), and HF hospitalization (HFH) between both groups and the number of HFH before and after CA in each group. Multivariate analysis was performed to identify the predictors of MACE in patients with HFpEF. The incidence of MACE was comparable between the groups (following the first procedure: HFpEF: 23%, 4.7/100 person‐years, vs. systolic HF: 28%, 6.6/100 person‐years, P = 0.18; last procedure: 20%, 4.8/100 person‐years, vs. 24%, 6.9/100 person‐years, P = 0.21). Although the incidence of HFH was lower in patients with HFpEF than in those with systolic HF (first procedure: 14%, 2.9/100 person‐years, vs. 24%, 5.7/100 person‐years, P = 0.07; last procedure: 11%, 2.5/100 person‐years, vs. 24%, 6.9/100 person‐years, P = 0.01), the incidence of CVH was higher (first procedure: 8%, 1.7/100 person‐years, vs. 5%, 1.2/100 person‐years, P = 0.74; last procedure: 6%, 1.4/100 person‐years, vs. 2%, 0.5/100 person‐years, P = 0.4). The number of HFH significantly decreased in both groups after CA (HFpEF: 1 hospitalization [the first and third quartiles: 0, 1] in pre‐CA, vs. 0 hospitalizations [0, 0] in post‐CA, P < 0.0001; systolic HF: 1 hospitalization [0, 1], vs. 0 hospitalizations [0, 0], P < 0.005). The proportion of HFH among total clinical events was significantly smaller in patients with HFpEF than in those with systolic HF (following the first procedure: 56% vs. 88%, P < 0.005; last procedure: 52% vs. 92%, P < 0.005). Conclusions CA for AF could be beneficial for patients with HFpEF, similar to those with systolic HF. However, clinical events other than HFH should be considered cautiously in such patients

The Differential Prognostic Impact of Long-Duration Atrial High-Rate Episodes Detected by Cardiac Implantable Electronic Devices between Patients with and without a History of Atrial Fibrillation

Long-duration atrial high-rate episodes (AHREs) monitored using cardiac implantable electronic devices (CIEDs) can predict long-term major adverse cardiovascular events (MACEs). This study aimed to compare the impact of long-duration AHRE on MACE development between patients with and without a history of atrial fibrillation (AF). This single-center observational study included 132 CIED-implanted patients with AHREs detected via remote monitoring. The population was dichotomized into groups: with (n = 69) and without (n = 63) AF. In each group, cumulative incidences of MACEs comprising all-cause deaths, heart failure hospitalizations, strokes, and acute coronary syndromes were compared between patients with AHRE durations of &ge;24 h and &lt;24 h. Multivariate analysis was performed to identify predictors of MACEs among patients without AF. MACE incidence was significantly higher in patients with AHRE &ge;24 h than in those with &lt;24 h in the group without AF (92% vs. 30%, p = 0.005). MACE incidence did not significantly differ between AHRE &ge;24 h and &lt;24 h in the group with AF (54% vs. 26%, p = 0.44). After a multivariate adjustment, AHRE duration of &ge;24 h emerged as the only independent predictor of MACEs among patients without AF (p = 0.03). In conclusion, a long-duration AHRE was prognostic in patients without a history of AF but not in patients with a history of AHREs

Impact of Atrial Tachyarrhythmia Recurrence on the Development of Long‐Term Adverse Clinical Events Following Catheter Ablation in Patients With Atrial Fibrillation With Systolic Impairment: A Single‐Center Observational Study

Background Catheter ablation can improve long‐term prognosis of patients with atrial fibrillation with systolic impairment. However, atrial tachyarrhythmia (ATA) recurrence increases during long‐term follow‐up. We aimed to investigate the impact of ATA recurrence on the development of long‐term adverse clinical events following catheter ablation for atrial fibrillation and to identify predictors for the development of adverse clinical events. Methods and Results This single‐center observational study included 75 patients with systolic impairment (left ventricular ejection fraction <50%) who underwent the first catheter ablation procedure for atrial fibrillation at our institution (median follow‐up period: 3.5 [range: 2.4–4.7] years). We compared the cumulative incidence of adverse clinical events (all‐cause death, heart failure hospitalization, stroke, or acute myocardial infarction) between the groups with and without ATA recurrence following the first and last procedures. Multivariable analyses were performed to identify predictors for developing adverse clinical events. Twenty‐one patients (28%) developed adverse clinical events at a median of 2.2 (range: 0.64–2.8) years following the first procedure. The proportion of freedom from adverse clinical events following the first procedure was significantly lower in the ATA recurrence group than in the nonrecurrence group (41% [n=40] versus 95% [n=35], P<0.0005); the proportion following the last procedure also showed a similar tendency (35% [n=26] versus 57% [n=49], P<0.0001). ATA recurrence emerged as an independent predictor for adverse clinical events following both procedures after multivariable adjustment. Conclusions ATA recurrence following catheter ablation procedure could predict adverse clinical events in patients with atrial fibrillation with systolic impairment

Nuclear translocation of calmodulin in pathological cardiac hypertrophy originates from ryanodine receptor bound calmodulin

In cardiac myocytes Calmodulin (CaM) bound to the ryanodine receptor (RyR2) constitutes a large pool of total myocyte CaM, but the CaM-RyR2 affinity is reduced in pathological conditions. Knock-in mice expressing RyR2 unable to bind CaM also developed hypertrophy and early death. However, it is unknown whether CaM released from this RyR2-bound pool participates in pathological cardiac hypertrophy. We found that angiotensin II (AngII) or phenylephrine (PE) both cause CaM to dissociate from the RyR2 and translocate to the nucleus. To test whether this nuclear CaM accumulation depends on CaM released from RyR2, we enhanced CaM-RyR2 binding affinity (with dantrolene), or caused CaM dissociation from RyR2 (using suramin). Dantrolene dramatically reduced AngII- and PE-induced nuclear CaM accumulation. Conversely, suramin enhanced nuclear CaM accumulation. This is consistent with nuclear CaM accumulation coming largely from the CaM-RyR2 pool. CaM lacks a nuclear localization signal (NLS), but G-protein coupled receptor kinase 5 (GRK5) binds CaM, has a NLS and translocates like CaM in response to AngII or PE. Suramin also promoted GRK5 nuclear import, and caused nuclear export of histone deacetylase 5 (HDAC5). Dantrolene prevented these effects. After 2-8 weeks of pressure overload (TAC) CaM binding to RyR2 was reduced, nuclear CaM and GRK5 were both elevated and there was enhanced nuclear export of HDAC5. Stress (acute AngII or TAC) causes CaM dissociation from RyR2 and translocation to the nucleus with GRK5 with parallel HDAC5 nuclear export. Thus CaM dissociation from RyR2 may be an important step in driving pathological hypertrophic gene transcription