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

BACKGROUND: Heart 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. METHODS: From 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). RESULTS: Fifty-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 < 0.01), NT-proBNP (k = 23; SMD: 0.33, 95%CI 0.25-0.40, I2 = 72%, P < 0.01), and CRP (k = 8; SMD: 0.30, 95%CI 0.12-0.48, I2 = 62%, P < 0.01) vs. patients with HF without frailty. Using meta-regression, body mass index (BMI) and age were deemed potential moderators of these findings. CONCLUSIONS: Frailty 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.

In symptomatic AF, catheter ablation vs. medical therapy reduced depression and anxiety symptoms at 12 mo.

SOURCE CITATION: Al-Kaisey AM, Parameswaran R, Bryant C, et al. Atrial fibrillation catheter ablation vs medical therapy and psychological distress: a randomized clinical trial. JAMA. 2023;330:925-933. 37698564.

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.

Incidence of Mid-Term Prognostic Events in Patients With Acute Coronary Syndrome During the Late 2010s in 2 Tertiary Hospitals in a Rural Area of Japan　- A Temporal Comparison.

Background: Data on the incidence of mid-term prognostic events in patients who developed acute coronary syndrome (ACS) in the late 2010s are scarce. Methods and Results: We retrospectively included and collected data for 889 patients with ACS (ST-elevation myocardial infarction [STEMI]/non-ST-elevation ACS [NSTE-ACS]) discharged alive from 2 tertiary hospitals in Izumo City, in rural Japan, between August 2009 and July 2018. Patients were divided into 3 time groups (T1: August 2009-July 2012; T2: August 2012-July 2015; T3: August 2015-July 2018). The cumulative incidence of major adverse cardiovascular events (MACE; comprising all-cause death, recurrent ACS, and stroke), major bleeding, and heart failure hospitalization within 2 years of discharge was compared among the 3 groups. The incidence of freedom from MACE was significantly higher in the T3 group than in the T1 and T2 groups (93 [95% confidence interval {CI} 90-96%] vs. 86% [95% CI 83-90] and 89% [95% CI 90-96], respectively; P=0.03). There was a tendency for a higher incidence of STEMI among patients in T3 (P=0.057). The incidence of NSTE-ACS was comparable among the 3 groups (P=0.31), as was the incidence of major bleeding and hospitalization for heart failure. Conclusions: The incidence of mid-term MACE in patients who developed ACS during the late 2010 s (2015-2018) was lower than that in prior periods (2009-2015).

RyR2-targeting therapy prevents left ventricular remodeling and ventricular tachycardia in post-infarction heart failure.

BACKGROUND: Dantrolene binds to the Leu601-Cys620 region of the N-terminal domain of cardiac ryanodine receptor (RyR2), which corresponds to the Leu590-Cys609 region of the skeletal ryanodine receptor, and suppresses diastolic Ca2+ leakage through RyR2. OBJECTIVE: We investigated whether the chronic administration of dantrolene prevented left ventricular (LV) remodeling and ventricular tachycardia (VT) after myocardial infarction (MI) by the same mechanism with the mutation V3599K of RyR2, which indicated that the inhibition of diastolic Ca2+ leakage occurred by enhancing the binding affinity of calmodulin (CaM) to RyR2. METHODS AND RESULTS: A left anterior descending coronary artery ligation MI model was developed in mice. Wild-type (WT) were divided into four groups: sham-operated mice (WT-Sham), sham-operated mice treated with dantrolene (WT-Sham-DAN), MI mice (WT-MI), and MI mice treated with dantrolene (WT-MI-DAN). Homozygous V3599K RyR2 knock-in (KI) mice were divided into two groups: sham-operated mice (KI-Sham) and MI mice (KI-MI). The mice were followed for 12 weeks. Survival was significantly higher in the WT-MI-DAN (73%) and KI-MI groups (70%) than the WT-MI group (40%). Echocardiography, pathological tissue, and epinephrine-induced VT studies showed that LV remodeling and VT were prevented in the WT-MI-DAN and KI-MI groups compared to the WT-MI group. An increase in diastolic Ca2+ spark frequency and a decrease in the binding affinity of CaM to the RyR2 were observed at 12 weeks after MI in the WT-MI group, although significant improvements in these values were observed in the WT-MI-DAN and KI-MI groups. CONCLUSIONS: Pharmacological or genetic stabilization of RyR2 tetrameric structure improves survival after MI by suppressing LV remodeling and proarrhythmia.

Acute heart failure following the initiation of cabozantinib, a multikinase inhibitor: A case report.

Cabozantinib is a multikinase inhibitor that exerts anticancer activity against malignancies such as renal tumors and leukemia. Although other agents that belong to the same category can cause cardiotoxicity, there is a paucity of information on the safety profile of cabozantinib. Herein, we present the case of a 62-year-old woman who developed acute heart failure (HF) following the initiation of cabozantinib for a metastatic renal tumor. She had no history of cardiovascular disease. Echocardiography prior to chemotherapy revealed normal cardiac function. However, she developed sudden onset of dyspnea 23 days following cabozantinib initiation. The chest X-ray showed newly developed congestion and cardiomegaly, and echocardiography revealed severe impairment of systolic and diastolic function. She was referred to the intensive care unit for non-invasive positive pressure ventilation and infusion of inotropes. The cardiac function fairly recovered on day 46; thereafter, supportive therapy, followed by guideline-directed medical therapy for HF with reduced ejection fraction was provided. We describe the first case of severe acute HF following cabozantinib initiation without underlying heart disease. Clinicians should plan follow-up schedules and be cautious of the development of HF when they initiate the agent, even if patients appear to have a low cardiovascular disease risk. Learning objectives: •We report the first case of acute heart failure following cabozantinib initiation without an underlying heart disease.•Prompt discontinuation of the agent and supportive therapy with guideline-directed medications can allow adequate recovery of cardiac function, even if the severity of heart failure is high.•Careful follow-up following the initiation is warranted when clinicians plan to initiate cabozantinib, even if patients appear to have low risk of cardiovascular disease.

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

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 ≥24 h and <24 h. Multivariate analysis was performed to identify predictors of MACEs among patients without AF. MACE incidence was significantly higher in patients with AHRE ≥24 h than in those with <24 h in the group without AF (92% vs. 30%, p = 0.005). MACE incidence did not significantly differ between AHRE ≥24 h and <24 h in the group with AF (54% vs. 26%, p = 0.44). After a multivariate adjustment, AHRE duration of ≥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.

Enhanced oxidative stress and presence of ventricular aneurysm for risk prediction in cardiac sarcoidosis.

OBJECTIVE: Sudden cardiac death (SCD) is the major cause of death in cardiac sarcoidosis (CS). We aimed to identify the prognostic markers for sustained ventricular tachycardia (sVT) and SCD in patients with CS. METHODS: We performed a prospective observational cohort study for patients with CS diagnosed according to the Japanese or Heart Rhythm Society guidelines between June 2008 and March 2020 in our hospital. The primary endpoint was a composite of the first sVT and SCD. The levels of urinary 8-hydroxy-2'-deoxyguanosine (U-8-OHdG), a marker of oxidative DNA damage that reflects the inflammatory activity of CS, other biomarkers, and indices of cardiac function and renal function were measured on admission. RESULTS: Eighty-nine consecutive patients with CS were enrolled; 28 patients with no abnormal 18F-fluorodeoxyglucose (18F-FDG) accumulation in the heart were excluded and 61 patients with abnormal 18F-FDG accumulation were followed up for a median of 46 months (IQR: 20-84). During the follow-up period, 15 of 61 patients showed sVT (n=12) or SCD (n=3). A Cox proportional hazard model showed that U-8-OHdG concentration and presence of ventricular aneurysm (VA) were independent predictors of first sVT/SCD. The cut-off U-8-OHdG concentration for predicting first sVT/SCD was 14.9 ng/mg·Cr. Patients with U-8-OHdG concentration ≥14.9 ng/mg·Cr and VA showed a significantly increased risk of sVT/SCD. CONCLUSIONS: U-8-OHdG and presence of VA were powerful predictors of first sVT/SCD in patients with CS, facilitating the stratification of cardiac events and providing relevant information about the substrates of ventricular tachycardia.