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 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.

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.

Trends Over Time in the Incidences of ST-Segment Elevation Myocardial Infarction and Non-ST-Segment Elevation Myocardial Infarction During the Past Decade in a Rural Japanese High-Aged Population.

BACKGROUND: In developed countries, the incidence of non-ST-segment elevation myocardial infarction (NSTEMI) has outpaced that of ST-segment elevation myocardial infarction (STEMI). However, whether this trend is observed in Japan, in which the aging of society is rapidly progressing, remains to be elucidated.Methods and Results:This study retrospectively investigated the trends over time in the incidence of acute coronary syndrome (ACS) between August 2009 and July 2019 at 2 institutions in Izumo City (in rural Japan), which has an elderly population. Crude and age-sex-adjusted incidences of total ACS, STEMI, and non-ST-segment elevation-ACS (NSTE-ACS; including NSTEMI and unstable angina pectoris) were calculated for each year. In the total population, factors associated with the development of NSTEMI were evaluated by multivariate analysis. In total, 1,087 patients were enrolled. The age-adjusted incidence of NSTE-ACS in male patients aged ≥75 years showed a significantly increasing trend. The proportion of NSTEMI per total ACS cases showed a significantly increasing trend over the entire study period. In the multivariate analysis, pre-development use of ≥3 medications for comorbidities was associated with the development of NSTEMI, independent of high-sensitivity cardiac troponin assay use. CONCLUSIONS: This study demonstrated an increasing trend in the incidence of NSTEMI in a rural high-aged Japanese population. In addition to the widespread use of high-sensitivity cardiac troponin assays, early medication use for comorbidities might have contributed to this trend.

Association Between Atrial High-Rate Episodes and Ischemic/Major Bleeding Events in Patients With a Cardiac Implantable Electronic Device　- A 10-Year, Single-Center Historical Cohort Study.

BACKGROUND: An association between atrial high-rate episode (AHRE) and stroke has been reported, although data for the Asian population are limited. This study aimed to investigate the role of AHRE in ischemic and major bleeding events in patients who underwent a cardiac implantable electronic device (CIED) procedure.Methods and Results:This single-center historical cohort study included 710 patients (age: 78±11 years, 374 women) who underwent a CIED-related procedure between October 2009 and September 2019 at Shimane Prefectural Central Hospital (median follow-up period: 4.5 [2.5, 7] years, 3439 person-years). Based on the maximum AHRE burden, patients were divided into: (1) <6 min; (2) ≥6 min to 24-h; and (3) ≥24-h groups. The cumulative incidence of ischemic (ischemic stroke, systemic embolism, and transient ischemic attack) and major bleeding (≥3 Bleeding Academic Research Consortium bleeding criteria) events after the procedure were compared. Uni- and multivariate analyses were performed to identify factors associated with these events. The incidence of both events increased with the rising AHRE burden, being significantly higher in the ≥24-h group than in the <6 min group. Multivariate analysis found age ≥85 years to be the only independent factor associated with both events. CONCLUSIONS: Longer AHRE duration is associated with a high number of major bleeding and ischemic events. Monitoring these bleeding risks is mandatory when clinicians are considering anticoagulation therapy for such patients.

Successful ablation of biatrial tachycardia with preserved electrical activation of left atrial appendage by unidirectional connection via Bachmann's bundle: A case report.

A 57-year-old man underwent his seventh ablation session for atrial tachycardia (AT). His previous ablations involved several regions of the right atrium (RA) and left atrium (LA). The AT was characterized as biatrial tachycardia with a circuit involving the mitral annulus and septal RA. The AT was terminated by ablation through the insertion site of Bachmann's bundle (BB) in both atria. After 3 months, the patient underwent his eighth ablation session because of AT recurrence. Activation maps showed that the connection from the RA to LA and vice versa was maintained via BB and the coronary sinus, respectively. The ablation target to interrupt the AT circuit was the mitral isthmus (MI), not BB, because BB supplied the electrical activation of the left atrial appendage (LAA) via a unidirectional electrical connection from the RA to LA. Ablation attempts from within the coronary sinus were performed to target the epicardial connection in the MI and led to complete blockage of the connection from the LA to RA. Otherwise, the connection from the RA to LA was preserved via BB. The patient was free of symptoms and anti-arrhythmic drugs at the 4-month follow-up. However, he had a high risk of electrical isolation of the LAA because extensive ablations had been performed; the strategy of targeting the MI contributed to the balance between preserving the electrical activation of the LAA and treating the biatrial tachycardia. Verification of the connective pathway between the two atria might be helpful to determine the optimal target.

Detection of Active Inflammation Status Around Ventricular Aneurysms in Patients With Cardiac Sarcoidosis.

BACKGROUND: Little is known about the pattern of isotope accumulation in the heart on 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography in patients with cardiac sarcoidosis (CS) complicated by ventricular aneurysm (VA).Methods and Results:We prospectively enrolled 82 consecutive patients with CS; 54 patients with active CS (presence of abnormal 18F-FDG accumulation in the heart) were subdivided into VA (n=17) and non-VA groups (n=37). Strong 18F-FDG accumulation surrounding the VA and its disappearance in the VA center was observed in all patients with VA, probably because of scar formation at the VA. Peak standardized uptake value was higher around the VA than in the VA center (5.1±2.1 vs. 2.2±0.6, P=0.0003) and the VA center had no 18F-FDG accumulation (VA center: 2.2±0.6 vs. control area: 2.1±0.6, P=0.37). On the other hand, in non-VA patients with LV wall thinning (n=28), 18F-FDG accumulation was significantly high, even in the area of LV wall thinning (LV wall thinning area: 3.1±0.8 vs. control area: 2.0±0.6, P=0.00002). CONCLUSIONS: A pattern of strong 18F-FDG accumulation surrounding the VA and its disappearance in the VA center might be characteristic in patients with CS complicated by VA. Careful attention to FDG uptake would further elucidate CS pathophysiology and aid in the early treatment of VA.

Addition of a ß1-Blocker to Milrinone Treatment Improves Cardiac Function in Patients with Acute Heart Failure and Rapid Atrial Fibrillation.

BACKGROUND: Tachycardia worsens cardiac performance in acute decompensated heart failure (ADHF). We investigated whether heart rate (HR) optimization by landiolol, an ultra-short-acting ß1-selective blocker, in combination with milrinone improved cardiac function in patients with ADHF and rapid atrial fibrillation (AF). METHODS AND RESULTS: We enrolled9 ADHF patients (New York Heart Association classification IV; HR, 138 ± 18 bpm; left ventricular [LV] ejection fraction, 28 ± 8%; cardiac index [CI], 2.1 ± 0.3 L/min-1/m-2; pulmonary capillary wedge pressure [PCWP], 24 ± 3 mm Hg), whose HRs could not be reduced using standard treatments, including diuretics, vasodilators, and milrinone. Landiolol (1.5-6.0 µg/kg-1/min-1, intravenous) was added to milrinone treatment to study its effect on hemodynamics. The addition of landiolol (1.5 µg/kg-1/min-1) significantly reduced HR by 11% without changing systolic blood pressure (BP) and resulted in a significant decrease in PCWP and a significant increase in stroke volume index (SVI), suggesting that HR reduction restores incomplete LV relaxation. Administration of more than 3.0 µg/kg-1/min-1 of landiolol decreased BP, CI, and SVI. CONCLUSION: The addition of landiolol at doses of <3.0 µg/kg/min to milrinone improved cardiac function in decompensated chronic heart failure with rapid atrial fibrillation by selectively reducing HR.

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.

Natriuretic peptides and C-reactive protein in in heart failure and malnutrition: a systematic review and meta-analysis.

BACKGROUND: Heart failure (HF) and malnutrition exhibit overlapping risk factors, characterized by increased levels of natriuretic peptides and an inflammatory profile. The aim of this study was to compare the differences in plasma brain natriuretic peptide (BNP), N-terminal-pro B-type natriuretic peptide (NT-proBNP), and C-reactive protein (CRP) in patients with HF and malnutrition versus normal nutrition. METHODS: From inception until July 2023, the databases, PubMed, Scopus, Web of Science, and Cochrane Library were searched. To examine the association among malnutrition [controlling nutritional status (CONUT) score ≥2; Geriatric Nutritional Risk Index (GNRI) score <92] with BNP, NT-proBNP and CRP in patients with HF, a meta-analysis using a random-effects model was conducted (CRD42023445076). RESULTS: A significant association of GNRI with increased levels of BNP were demonstrated [mean difference (MD): 204.99, 95% confidence interval (CI) (101.02, 308.96, I2 = 88%, P < 0.01)], albeit no statistically significant findings were shown using CONUT [MD: 158.51, 95% CI (-1.78 to 318.79, I2 = 92%, P = 0.05)]. GNRI [MD: 1885.14, 95% CI (1428.76-2341.52, I2 = 0%, P < 0.01)] and CONUT [MD: 1160.05, 95% CI (701.04-1619.07, I2 = 0%, P < 0.01)] were associated with significantly higher levels of NT-proBNP. Patients with normal GNRI scores had significantly lower levels of CRP [MD: 0.50, 95% CI (0.12-0.88, I2 = 87%, P = 0.01)] whereas significantly higher levels of CRP were observed in those with higher CONUT [MD: 0.40, 95% CI (0.08-0.72, I2 = 88%, P = 0.01)]. Employing meta-regression, age was deemed a potential moderator between CRP and GNRI. CONCLUSIONS: Normal nutrition scores in patients with HF are linked to lower BNP, NT-proBNP, and CRP levels compared with malnourished counterparts. Despite the significant link between CRP and malnutrition, their relationship may be influenced in older groups considering the sensitivity of GNRI due to ageing factors.

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).

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.