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1.
Can J Cardiol ; 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39270750

RESUMEN

BACKGROUND: Ultrasound may be helpful for muscle mass assessment in heart failure (HF). We aimed to determine the feasibility and prognostic implications of ultrasound-measured quadriceps muscle thickness (QMT) in older patients with HF. METHODS: This was a post-hoc analysis of a multicenter prospective cohort study including patients hospitalized for HF aged ≥ 65 years. QMT at rest and during isometric contractions was measured in the supine position using ultrasound before discharge. RESULTS: The interobserver agreement for measuring QMT was excellent, with intraclass correlation coefficients (ICCs) of 0.979 (95% confidence interval [CI] 0.963-0.988) at rest and 0.997 (95% CI 0.994-0.998) during isometric contraction. The intra-observer reproducibility was also excellent (ICC >0.92). Of the 595 patients (median age: 81 years, 56% male), median QMT at rest and during contraction were 18.9 mm and 24.9 mm, respectively. The patients were grouped according to sex-specific tertiles of height-adjusted QMT. During the median follow-up of 735 days, 157 deaths occurred, and Kaplan-Meier curve analysis showed that the lowest tertile of the height-adjusted QMT was associated with higher mortality. Cox proportional hazard analysis revealed that thinner height-adjusted QMT was independently associated with higher mortality, even after adjusting for conventional risk factors (per 1 mm/m increase: hazard ratio [HR] 0.94, 95% CI 0.89-0.99, P=0.030 [at rest] and HR 0.94, 95% CI 0.90-0.99, P=0.015 [during isometric contraction]). CONCLUSIONS: Ultrasound-measured QMT in older patients with HF is feasible, and thinner height-adjusted QMT at rest and during isometric contraction was independently associated with higher mortality.

2.
JACC Adv ; 3(8): 101105, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39105116

RESUMEN

Background: Ventricular arrhythmia (VA) is a life-threatening condition associated with cardiac sarcoidosis (CS). Right bundle branch block (RBBB) is a common conduction disorder in CS; however, its association with VA remains unknown. Objectives: This study aimed to investigate the relationship between RBBB and VA in patients with CS. Methods: This was a post hoc analysis of ILLUMINATE-CS (Illustration of the Management and Prognosis of Japanese Patients with Cardiac Sarcoidosis), a multicenter, retrospective, and observational study that evaluated the clinical characteristics and prognosis of CS. Eligible patients were divided into two groups based on the presence or absence of RBBB at the time of diagnosis. The primary outcome was serious ventricular arrhythmia events (SVAEs), defined as a combination of sudden cardiac death and documented ventricular fibrillation, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator therapy. Results: Overall, 312 patients were studied, with 155 (49.7%) patients presenting with RBBB (RBBB group). Patients in the RBBB group had a higher prevalence of basal interventricular septum (IVS) thinning and prominent late gadolinium enhancement in the basal IVS on cardiac magnetic resonance imaging than those in the non-RBBB group. During a median follow-up of 3.0 years (IQR: 1.6-6.0 years), 66 patients experienced SVAE. In multivariable Cox regression analysis, the RBBB group was independently associated with a higher incidence of SVAEs (HR: 1.93 [95% CI: 1.14-3.28]; P = 0.015). Conclusions: In patients with CS, RBBB was an independent predictor of SVAEs, which might reflect the specific scar distribution that is predominant in the IVS.

3.
Int J Cardiol Heart Vasc ; 53: 101473, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39139610

RESUMEN

Background: Nonsteroidal immunosuppressive therapy is a potential therapeutic strategy for cardiac sarcoidosis. However, it is not recommended as an established treatment option. This study aimed to demonstrate the clinical outcomes of patients with cardiac sarcoidosis using nonsteroidal immunosuppressants through the ILLUstration of the Management and PrognosIs of JapaNese PATiEnts with Cardiac Sarcoidosis multicenter retrospective registry. Methods: From a cohort of 512 patients, 426 who received corticosteroid therapy and 26 who received other immunosuppressive therapy were included for analysis. Clinical outcomes included all-cause death, fatal ventricular arrhythmic events (FVAE), and worsening heart failure with hospitalization. Results: Nonsteroidal immunosuppressants were used for retained fluorodeoxyglucose uptake in the heart (n = 14), corticosteroid side effects (n = 7), ventricular arrhythmia (n = 4), complete atrioventricular block (n = 2), worsened extracardiac sarcoidosis (n = 2), and other reasons (n = 2). They comprised of methotrexate (n = 20), cyclosporine (n = 2), cyclophosphamide (n = 2), and azathioprine (n = 3). After the addition of a nonsteroidal immunosuppressant, corticosteroids were reduced in 14 of 26 patients (5 [5-17] mg), although no patient discontinued corticosteroids. Of the 14 patients, decreased fluorodeoxyglucose uptake was observed in seven at follow-up. Clinical outcomes were observed in 11 patients (42.3 %). Detected events included all-cause death in five patients (19.2 %), FVAE in four (15.4 %), and worsening heart failure with hospitalization in five (19.2 %), with some overlap. Conclusions: Nonsteroidal immunosuppressive therapy may be a possible treatment option for patients who are not stabilized with corticosteroids alone or develop corticosteroid side effects.

4.
Eur J Prev Cardiol ; 31(11): 1363-1369, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-38573843

RESUMEN

AIMS: This study aimed to investigate the prevalence, clinical characteristics, and prognostic value of bendopnea in older patients hospitalized for heart failure. METHODS AND RESULTS: This post hoc analysis was performed using two prospective, multicentre, observational studies: the FRAGILE-HF (main cohort) and SONIC-HF (validation cohort) cohorts. Patients were categorized based on the presence of bendopnea, which was evaluated before discharge. The primary endpoint was 2-year all-cause mortality after discharge. Among the 1243 patients (median age, 81 years; 57.2% male) in the FRAGILE-HF cohort and 225 (median age, 79 years; 58.2% men) in the SONIC-HF cohort, bendopnea was observed in 31 (2.5%) and 10 (4.4%) patients, respectively. Over a 2-year follow-up period, all-cause death occurred in 20.8 and 21.9% of the patients in the FRAGILE-HF and SONIC-HF cohorts, respectively. Kaplan-Meier survival curves demonstrated significantly higher mortality rates in patients with bendopnea than in those without bendopnea in the FRAGILE-HF (log-rank P = 0.006) and SONIC-HF cohorts (log-rank P = 0.014). Cox proportional hazard analysis identified bendopnea as an independent prognostic factor for all-cause mortality in both the FRAGILE-HF [hazard ratio (HR) 2.11, 95% confidence interval (CI) 1.18-3.78, P = 0.012] and SONIC-HF cohorts (HR 4.20, 95% CI 1.63-10.79, P = 0.003), even after adjusting for conventional risk factors. CONCLUSION: Bendopnea was observed in a relatively small proportion of older patients hospitalized for heart failure before discharge. However, its presence was significantly associated with an increased risk of all-cause mortality.


This study investigated how common it is for older patients with heart failure to have trouble breathing when they bend forward, and whether this affects their chances of survival. The study found that although this problem is not very common, it is linked to a higher risk of death.


Asunto(s)
Insuficiencia Cardíaca , Humanos , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/diagnóstico , Masculino , Femenino , Anciano , Prevalencia , Anciano de 80 o más Años , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Factores de Tiempo , Causas de Muerte , Factores de Edad , Medición de Riesgo , Disnea/epidemiología , Disnea/mortalidad , Japón/epidemiología
5.
RSC Med Chem ; 15(4): 1274-1282, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38665825

RESUMEN

We recently reported novel purine-based CK2α inhibitors using the solvent ordering-based method as virtual screening. Among these, the X-ray crystal structure of a complex with CK2α was determined. The results showed that the crystalline water molecules observed in many previously reported complex structures of CK2α and its inhibitors had been eliminated. We then proposed a structure-based drug design. Since the removal of water molecules would be detrimental to inhibitor binding, new groups of compounds were designed by changing the position of the carboxy group located at the point where a water molecule would be present so as not to eliminate it. Compounds with (E)-2-carboxyethenyl and 3-carboxyphenyl substituted at the 2-position on the purine scaffold showed much higher inhibitory potency than 4-carboxyphenyl derivatives. Furthermore, in the presence of a 4-fluorophenyl group at the 9-position on the purine scaffold, the inhibitory activity of the 3-carboxyphenyl derivative against CK2α was 0.18 µM, a 167-fold improvement compared to the 4-carboxyphenyl derivative. The strategy of leaving crystalline water can significantly increase inhibitory activity.

6.
J Am Heart Assoc ; 13(6): e032047, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38456399

RESUMEN

BACKGROUND: Current guidelines recommend placing an implantable cardiac defibrillator for patients with cardiac sarcoidosis and a severely impaired left ventricular ejection fraction (LVEF) of ≤35%. In this study, we determined the association between mild or moderate LVEF impairment and fatal ventricular arrhythmic event (FVAE). METHODS AND RESULTS: We retrospectively analyzed 401 patients with cardiac sarcoidosis without sustained ventricular arrhythmia at diagnosis. The primary end point was an FVAE, defined as the combined endpoint of documented ventricular tachycardia or ventricular fibrillation and sudden cardiac death. Two cutoff points for LVEF were used: a sex-specific lower threshold of normal range of LVEF (52% for men and 54% for women) and an LVEF of 35%, which is used in the current guidelines. During a median follow-up of 3.2 years, 58 FVAEs were observed, and the 5- and 10-year estimated incidences of FVAEs were 16.8% and 23.0%, respectively. All patients were classified into 3 groups according to LVEF: impaired LVEF group, mild to moderate impairment of LVEF group, and maintained LVEF group. Multivariable competing risk analysis showed that both the impaired LVEF group (hazard ratio [HR], 3.24 [95% CI, 1.49-7.04]) and the mild to moderate impairment of LVEF group (HR, 2.16 [95% CI, 1.04-4.46]) were associated with a higher incidence of FVAEs than the maintained LVEF group after adjustment for covariates. CONCLUSIONS: Patients with cardiac sarcoidosis are at a high risk of FVAEs, regardless of documented ventricular arrhythmia at the time of diagnosis. In patients with cardiac sarcoidosis, mild to moderate impairment of LVEF is associated with FVAEs.


Asunto(s)
Desfibriladores Implantables , Miocarditis , Sarcoidosis , Masculino , Humanos , Femenino , Función Ventricular Izquierda , Volumen Sistólico , Estudios Retrospectivos , Sarcoidosis/complicaciones , Sarcoidosis/diagnóstico , Arritmias Cardíacas/etiología , Arritmias Cardíacas/complicaciones , Desfibriladores Implantables/efectos adversos , Muerte Súbita Cardíaca/epidemiología , Muerte Súbita Cardíaca/etiología , Miocarditis/complicaciones
7.
Int J Cardiol Heart Vasc ; 50: 101321, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38161782

RESUMEN

Background: Clinical characteristics and the risk of cardiovascular events in patients with cardiac sarcoidosis (CS) according to the age of initial diagnosis are unclear. Methods: This study is a sub-analysis of the ILLUMINATE-CS registry, which is a retrospective, multicenter registry that enrolled patients with CS between 2001 and 2017. Patients were divided into three groups according to the tertile of age at the time of initial diagnosis of CS. The study compared the clinical background at the time of CS diagnosis and the incidence rate of cardiac events across age categories. Results: A total of 511 patients were analyzed in this study. In baseline, older patients were more likely to be female. History of hypertension, heart failure admission, and atrioventricular block were more common in patients with older age. There was no significant difference in the history of ventricular arrhythmias and left ventricular ejection fraction among all age groups. During a median follow-up period of 3.2 [IQR: 1.7-4.2] years, 35 deaths, 56 heart failure hospitalization, and 98 fatal ventricular arrhythmias was observed. The incidence rate of all-cause death and heart failure hospitalization was significantly higher in patients with older age (p < 0.001), while there was no significant difference in the incidence rate of ventricular arrhythmia among age groups (p = 0.74). Conclusions: In patients with CS, the risk of all-cause death and heart failure hospitalization was higher in older patients compared with other age groups; however, the risk of ventricular arrhythmia was comparable across all age groups.

8.
ESC Heart Fail ; 11(2): 914-922, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38212896

RESUMEN

AIMS: This study aimed to determine whether there is a difference in the prognostic value of sarcopenia diagnosed using dual-energy X-ray absorptiometry (DEXA) and that predicted by prediction equations in older patients with heart failure (HF). METHODS AND RESULTS: We included 269 patients (aged ≥65 years) who were hospitalized for HF. We used two appendicular skeletal muscle mass (ASM) prediction equations: (i) Anthropometric-ASM, including age, sex, height, and weight, and (ii) Predicted-ASM, including sex, weight, calf circumference, and mid-arm circumference. ASM index (ASMI) was calculated by dividing the sum of the ASM in the extremities by the height squared (kg/m2). The cut-off values proposed by the Asian Working Group for Sarcopenia 2019 were used to define low ASMI. The prognostic endpoint was all-cause mortality. The median age of the cohort was 83 years [interquartile range (IQR): 75-87], and 135 patients (50.2%) were men. Sarcopenia diagnosed according to DEXA, Anthropometric measurements, and Predicted-ASM was observed in 134 (49.8%), 171 (63.6%), and 157 (58.4%) patients, respectively. During the median follow-up period of 690 days (IQR: 459-730), 54 patients (19.9%) died. DEXA-sarcopenia [hazard ratio (HR), 2.33; 95% confidence interval (CI), 1.26-4.31; P = 0.007] was associated with all-cause mortality after adjusting for pre-existing risk factors, whereas Predicted-sarcopenia (HR, 1.68; 95% CI, 0.87-3.25; P = 0.123) and Anthropometric-sarcopenia (HR, 1.64; 95% CI, 0.86-3.12; P = 0.132) were not. CONCLUSIONS: Sarcopenia diagnosed using DEXA was associated with poor prognosis in older patients with HF; however, the prediction equations were not.


Asunto(s)
Insuficiencia Cardíaca , Sarcopenia , Masculino , Humanos , Anciano , Anciano de 80 o más Años , Femenino , Sarcopenia/diagnóstico , Músculo Esquelético/patología , Absorciometría de Fotón/métodos , Insuficiencia Cardíaca/patología , Pronóstico
9.
Eur J Heart Fail ; 26(1): 77-86, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37823255

RESUMEN

AIM: Data on the clinical features and prognosis of patients with isolated cardiac sarcoidosis (iCS) are limited. This study evaluated the clinical characteristics and prognostic impact of iCS. METHODS AND RESULTS: This was a secondary analysis of the ILLUMINATE-CS study, a multicentre, retrospective registry investigating the clinical characteristics and prognosis of cardiac sarcoidosis. iCS was diagnosed according to the 2016 Japanese Circulation Society (JCS) guidelines. Clinical characteristics and prognosis were compared between patients with iCS and systemic cardiac sarcoidosis (sCS). The primary outcome was a combined endpoint of all-cause death, hospitalization for heart failure, or fatal ventricular arrhythmia events. Among 475 patients with CS (mean age, 62.0 ± 10.9 years; female ratio, 59%) diagnosed by the JCS guidelines, 119 (25.1%) were diagnosed with iCS. Patients with iCS had a higher prevalence of a history of atrial fibrillation or hospitalization for heart failure, or lower left ventricular ejection fraction than those with sCS. During a median follow-up of 42.3 (interquartile range, 22.8-72.5) months, 141 primary outcomes (29.7%) occurred. Cox proportional hazard analysis revealed that iCS was a significant risk factor for the primary outcome in the unadjusted model (hazard ratio [HR] 1.62; 95% confidence interval [CI] 1.12-2.34; p = 0.011). However, this association was not retained after adjustment for other covariates (adjusted HR 1.27; 95% CI 0.86-1.88; p = 0.226). CONCLUSIONS: Patients with iCS had more impaired cardiovascular function at the time of diagnosis than those with sCS. However, iCS was not independently associated with poor prognosis after adjustment for prognostic factors.


Asunto(s)
Cardiomiopatías , Insuficiencia Cardíaca , Miocarditis , Sarcoidosis , Humanos , Femenino , Persona de Mediana Edad , Anciano , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/complicaciones , Volumen Sistólico , Cardiomiopatías/diagnóstico , Cardiomiopatías/epidemiología , Cardiomiopatías/complicaciones , Estudios Retrospectivos , Función Ventricular Izquierda , Sarcoidosis/complicaciones , Sarcoidosis/diagnóstico , Sarcoidosis/epidemiología , Pronóstico , Miocarditis/complicaciones , Arritmias Cardíacas/complicaciones
10.
J Cardiol ; 83(4): 258-264, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37884192

RESUMEN

BACKGROUND: Appropriate evaluation of hemodynamic status is vital in the management of acute heart failure (AHF). We aimed to investigate the changes in echocardiographic parameters during very acute phases of AHF and their association with clinical outcomes. METHODS: Patients who were admitted to four Japanese hospitals with AHF were prospectively enrolled. Comprehensive echocardiography and B-type natriuretic peptide (BNP) were assessed both on admission and the second day. RESULTS: A total of 271 patients (80 ±â€¯12 years old, 52 % male) was included. Overall, transmitral E velocity, E/A, tricuspid regurgitation pressure gradient (TRPG), and inferior vena cava diameter significantly decreased, and stroke volume and left ventricular ejection fraction showed a significant increase by the second day, whereas E/e' did not change. On the second day, BNP increased in 50 patients (18 %). Despite similar baseline characteristics, patients with increased BNP showed a significantly smaller improvement in transmitral flow parameters (E and A velocity, E/A, and flow patterns) and a smaller decrease in TRPG compared with patients with decreased BNP. Other echocardiographic parameter changes were not different between the groups. A combination of improvement in transmitral flow and TRPG was significantly associated with 90-day and 1-year composite events of all-cause death and heart failure hospitalization after adjustment by the Get With the Guidelines-Heart Failure risk score. CONCLUSIONS: Echocardiographic parameters show a dynamic change in the very acute phase of AHF. Several parameters, such as the transmitral flow and TRPG might be useful in monitoring favorable hemodynamic change.


Asunto(s)
Insuficiencia Cardíaca , Función Ventricular Izquierda , Humanos , Masculino , Anciano , Anciano de 80 o más Años , Femenino , Volumen Sistólico , Ecocardiografía , Insuficiencia Cardíaca/diagnóstico por imagen , Hemodinámica , Péptido Natriurético Encefálico
11.
Eur Heart J Open ; 3(5): oead100, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37849788

RESUMEN

Aims: The prognostic value of the presence of atrial fibrillation (AF) in patients at the time of cardiac sarcoidosis (CS) diagnosis is unknown. This study aimed to investigate the association between AF at the time of CS diagnosis and patient prognosis. Methods and results: This study is a post-hoc analysis of Illustration of the Management and Prognosis of Japanese Patients with CS, a multicentre, retrospective observational study that evaluated the clinical characteristics and prognosis of patients with CS. The primary endpoint was the combined endpoint of all-cause death and hospitalization due to heart failure. After excluding patients with missing data about AF status, 445 patients (62 ± 11 years, 36% males) diagnosed with CS according to the Japanese current diagnostic guideline were analysed. Compared to patients without AF, patients with AF (n = 46, 10%) had higher levels of brain natriuretic peptide and a higher prevalence of heart failure hospitalizations. During a median follow-up period of 3.2 years (interquartile range, 1.7-5.8 years), 80 primary endpoints were observed. Kaplan-Meier curve analysis indicated that concomitant AF at the time of diagnosis was significantly associated with a high incidence of primary endpoints (log-rank P = 0.002). This association was retained after adjusting for known risk factors including log-transformed brain natriuretic peptide levels and left ventricular ejection fractions [hazard ratio, 1.96 (95% confidence interval, 1.05-3.65); P = 0.035]. Conclusion: The presence of AF at the time of CS diagnosis is associated with higher incidence of all-cause death and heart failure hospitalization.

12.
Coron Artery Dis ; 34(8): 545-554, 2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-37865863

RESUMEN

OBJECTIVES: The discordant results between fractional flow reserve (FFR) and resting full-cycle ratio (RFR) and the influence of angiographic characteristics on their correlation have not been sufficiently investigated. We aimed to identify angiographic characteristics that can predict FFR and RFR correlations using a novel angiographic scoring system. METHODS: This retrospective analysis included 220 patients with 252 intermediate coronary lesions assessed using FFR and RFR. Each branch distal to the target lesion was scored based on the vessel diameter (0 points: < 1.5 mm, 1 point: 1.5-2.0 mm, and 2 points: > 2.0 mm) measured using quantitative coronary angiography. The angiographic score was calculated by adding these scores. RESULTS: In a propensity score-matched cohort including 84 lesions (42 lesions in each low-and high-angiographic score group), the correlation between FFR and RFR in the high-angiographic score group (>4) was weaker than that in the low-score group (≤4) (Spearman's correlation: r = 0.44 vs. r = 0.80, P  < 0.01). Considering a threshold of functional myocardial ischemia as FFR ≤ 0.80 and RFR ≤ 0.89, the low-angiographic score group showed a significantly lower discordance rate of abnormal FFR/normal RFR than the high-angiographic score group (7.1% vs. 23.8%, P  = 0.03), whereas the discordance rates of normal FFR/abnormal RFR were similar in both groups (7.1% vs. 9.5%, P  = 0.69). CONCLUSION: This retrospective analysis highlights the influence of angiographic characteristics on the correlation between FFR and RFR. Our simple angiographic assessment method may be useful for interpreting physiological evaluations in daily clinical practice.


Asunto(s)
Estenosis Coronaria , Reserva del Flujo Fraccional Miocárdico , Humanos , Angiografía Coronaria , Reserva del Flujo Fraccional Miocárdico/fisiología , Estenosis Coronaria/diagnóstico por imagen , Estudios Retrospectivos , Valor Predictivo de las Pruebas , Cateterismo Cardíaco , Índice de Severidad de la Enfermedad , Vasos Coronarios/diagnóstico por imagen
14.
Chem Pharm Bull (Tokyo) ; 71(7): 558-565, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37394605

RESUMEN

Protein kinase CK2 (CK2) is involved in the suppression of gene expression, protein synthesis, cell proliferation, and apoptosis, thus making it a target protein for the development of therapeutics toward cancer, nephritis, and coronavirus disease 2019. Using the solvent dipole ordering-based method for virtual screening, we identified and designed new candidate CK2α inhibitors containing purine scaffolds. Virtual docking experiments supported by experimental structure-activity relationship studies identified the importance of the 4-carboxyphenyl group at the 2-position, a carboxamide group at the 6-position, and an electron-rich phenyl group at the 9-position of the purine scaffold. Docking studies based on the crystal structures of CK2α and inhibitor (PDBID: 5B0X) successfully predicted the binding mode of 4-(6-carbamoyl-8-oxo-9-phenyl-8,9-dihydro-7H-purin-2-yl) benzoic acid (11), and the results were used to design stronger small molecule targets for CK2α inhibition. Interaction energy analysis suggested that 11 bound around the hinge region without the water molecule (W1) near Trp176 and Glu81 that is frequently reported in crystal structures of CK2α inhibitor complexes. X-ray crystallographic data for 11 bound to CK2α was in very good agreement with the docking experiments, and consistent with activity. From the structure-activity relationship (SAR) studies presented here, 4-(6-Carbamoyl-9-(4-(dimethylamino)phenyl)-8-oxo-8,9-dihydro-7H-purin-2-yl) benzoic acid (12) was identified as an improved active purine-based CK2α inhibitor with an IC50 of 4.3 µM. These active compounds with an unusual binding mode are expected to inspire new CK2α inhibitors and the development of therapeutics targeting CK2 inhibition.


Asunto(s)
COVID-19 , Inhibidores de Proteínas Quinasas , Humanos , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/química , Quinasa de la Caseína II/genética , Quinasa de la Caseína II/metabolismo , Relación Estructura-Actividad , Ácido Benzoico , Purinas
15.
Heart ; 109(18): 1387-1393, 2023 08 24.
Artículo en Inglés | MEDLINE | ID: mdl-37185298

RESUMEN

OBJECTIVE: Owing to the paucity of data, this study aimed to investigate sex differences in clinical features and prognosis of patients with cardiac sarcoidosis (CS). METHODS: This study was a secondary analysis of the ILLUstration of the Management and prognosIs of JapaNese PATiEnts with Cardiac Sarcoidosis registry-a retrospective multicentre registry that enrolled patients with CS between 2001 and 2017. The primary outcome was potentially fatal ventricular arrhythmia events (pFVAEs)-a composite of sudden cardiac death, sustained ventricular tachycardia lasting >30 s, ventricular fibrillation or the requirement for implantable cardioverter defibrillator therapy. RESULTS: Of the 512 participants (mean age±SD 61.6±11.4 years), 329 (64.2%) were females. Both sexes had peak ages of 60-64 years at diagnosis. Male patients were younger and had a higher prevalence of coronary artery disease and lower left ventricular ejection fraction than female patients. During a median follow-up of 3 years (IQR 1.6-5.6), pFVAEs were observed in 99 patients, with males having a significantly higher risk than females (p=0.002). This association was retained even after adjustment for other risk factors for pFVAEs, including left ventricular ejection fraction (adjusted HR 1.80; 95% CI 1.08 to 3.01, p=0.025). CONCLUSION: Approximately two-thirds of patients with CS were females, with a peak age of approximately 60 years at clinical diagnosis in both sexes; male patients were younger than female patients. Male patients had a significantly higher risk of pFVAEs than female patients. TRIAL REGISTRATION NUMBER: UMIN000034974.


Asunto(s)
Cardiomiopatías , Desfibriladores Implantables , Miocarditis , Sarcoidosis , Taquicardia Ventricular , Humanos , Masculino , Femenino , Persona de Mediana Edad , Volumen Sistólico , Cardiomiopatías/diagnóstico , Cardiomiopatías/epidemiología , Cardiomiopatías/terapia , Caracteres Sexuales , Cardioversión Eléctrica/efectos adversos , Función Ventricular Izquierda , Sarcoidosis/complicaciones , Sarcoidosis/diagnóstico , Sarcoidosis/epidemiología , Pronóstico , Desfibriladores Implantables/efectos adversos , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/epidemiología , Taquicardia Ventricular/etiología , Muerte Súbita Cardíaca/epidemiología , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/prevención & control , Arritmias Cardíacas/complicaciones , Estudios Retrospectivos
16.
J Arrhythm ; 39(1): 10-17, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36733332

RESUMEN

Background: Micra leadless pacemaker is secured to the myocardium by engagement of at least 2/4 tines confirmed with pull and hold test. However, the pull and hold test is sometimes difficult to assess. This study was performed to evaluate whether the angle of the tines before the pull and hold test predicts engagement of the tines in Micra leadless pacemaker implantation. Methods: We retrospectively enrolled 93 consecutive patients (52.7% male, age 82.4 ± 9.4 years), who received Micra implantation from September 2017 to June 2020 at our institution. After deployment and before the pull and hold test, the angle of the visible tines to the body of the pacemaker was measured using the RAO view of the fluoroscopy image. The engagement of the tines was then confirmed with the pull and hold test. Results: A total of 326 tines were analyzed. The angle of the engaged tines was significantly lower than the non-engaged tines (9.2 degrees [4.0-14.0] vs. 16.6 degrees [14.2-18.8], p < .0001). All tines with angles <10 degrees were engaged. In higher angles, engagement could not be predicted. Conclusion: A low angle of the tines before the pull and hold test can predict engagement of the tines in Micra leadless pacemaker implantation. The tines which are already open after deployment may be presumed that they are engaged.

17.
J Am Heart Assoc ; 11(24): e025803, 2022 12 20.
Artículo en Inglés | MEDLINE | ID: mdl-36515231

RESUMEN

Background The prognostic role of BNP (B-type natriuretic peptide) in patients with cardiac sarcoidosis without evident heart failure is unknown. Methods and Results This is a post hoc analysis of ILLUMINATE-CS (Illustration of the Management and Prognosis of Japanese Patients With Cardiac Sarcoidosis), a multicenter, retrospective, and observational study that evaluated the clinical characteristics and prognosis of cardiac sarcoidosis. We analyzed patients with cardiac sarcoidosis without evident heart failure at the time of diagnosis. The association between baseline BNP levels and prognosis was investigated. The primary end point was the combined end point of all-cause death, heart failure hospitalization, and fatal ventricular arrhythmia. In total, 238 patients (61.0±11.1 years, 37% men) were analyzed, and 61 primary end points were observed during a median follow-up period of 3.0 (interquartile range, 1.7-5.8) years. Patients with high BNP (BNP above the median value of BNP) were older and had a lower renal function and left ventricular ejection fraction than those with low BNP values. Kaplan-Meier curve analysis indicated that high BNP levels were significantly associated with a high incidence of primary end points (log-rank P=0.004), and this association was retained even in multivariable Cox regression (hazard ratio, 2.06 [95% CI, 1.19-3.55]; P=0.010). Log-transformed BNP as a continuous variable was associated with the primary end point (hazard ratio, 2.12 [95% CI, 1.31-3.43]; P=0.002). Conclusions High baseline BNP level was an independent predictor of future adverse events in patients with cardiac sarcoidosis without heart failure at the time of diagnosis. Registration URL: https://www.umin.ac.jp/english/; Unique Identifier: UMIN-CTR: UMIN000034974.


Asunto(s)
Insuficiencia Cardíaca , Miocarditis , Sarcoidosis , Femenino , Humanos , Masculino , Biomarcadores , Insuficiencia Cardíaca/diagnóstico , Péptido Natriurético Encefálico , Pronóstico , Estudios Retrospectivos , Sarcoidosis/complicaciones , Sarcoidosis/diagnóstico , Sarcoidosis/epidemiología , Volumen Sistólico , Función Ventricular Izquierda , Persona de Mediana Edad , Anciano
18.
Eur Heart J ; 43(36): 3450-3459, 2022 09 21.
Artículo en Inglés | MEDLINE | ID: mdl-35781334

RESUMEN

AIMS: This study evaluated the prognosis and prognostic factors of patients with cardiac sarcoidosis (CS), an underdiagnosed disease. METHODS AND RESULTS: Patients from a retrospective multicentre registry, diagnosed with CS between 2001 and 2017 based on the 2016 Japanese Circulation Society or 2014 Heart Rhythm Society criteria, were included. The primary endpoint was a composite of all-cause death, hospitalization for heart failure, and documented fatal ventricular arrhythmia events (FVAE), each constituting exploratory endpoints. Among 512 registered patients, 148 combined events (56 heart failure hospitalizations, 99 documented FVAE, and 49 all-cause deaths) were observed during a median follow-up of 1042 (interquartile range: 518-1917) days. The 10-year estimated event rates for the primary endpoint, all-cause death, heart failure hospitalizations, and FVAE were 48.1, 18.0, 21.1, and 31.9%, respectively. On multivariable Cox regression, a history of ventricular tachycardia (VT) or fibrillation [hazard ratio (HR) 2.53, 95% confidence interval (CI) 1.59-4.00, P < 0.001], log-transformed brain natriuretic peptide (BNP) levels (HR 1.28, 95% CI 1.07-1.53, P = 0.008), left ventricular ejection fraction (LVEF) (HR 0.94 per 5% increase, 95% CI 0.88-1.00, P = 0.046), and post-diagnosis radiofrequency ablation for VT (HR 2.65, 95% CI 1.02-6.86, P = 0.045) independently predicted the primary endpoint. CONCLUSION: Although mortality is relatively low in CS, adverse events are common, mainly due to FVAE. Patients with low LVEF, with high BNP levels, with VT/fibrillation history, and requiring ablation to treat VT are at high risk.


Asunto(s)
Fibrilación Atrial , Insuficiencia Cardíaca , Sarcoidosis , Taquicardia Ventricular , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/epidemiología , Fibrilación Atrial/etiología , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/etiología , Humanos , Japón/epidemiología , Péptido Natriurético Encefálico/sangre , Sistema de Registros , Medición de Riesgo , Sarcoidosis/complicaciones , Sarcoidosis/diagnóstico , Sarcoidosis/epidemiología , Volumen Sistólico , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/epidemiología , Taquicardia Ventricular/etiología , Función Ventricular Izquierda
19.
Heart ; 108(23): 1887-1894, 2022 11 10.
Artículo en Inglés | MEDLINE | ID: mdl-35790370

RESUMEN

OBJECTIVES: Diagnosis of cardiac sarcoidosis (CS) without histological evidence remains controversial. This study aimed to compare characteristics and outcomes of histologically proven versus clinically diagnosed cases of CS, which were adjudicated using Heart Rhythm Society or Japanese Circulation Society criteria. METHODS: A total of 512 patients with CS (age: 62±11 years, female: 64.3%) enrolled in the multicentre registry were studied. Histologically confirmed patients were classified as 'biopsy-proven CS', while those with the presence of strongly suggestive clinical findings of CS without histological evidence were classified as 'clinical CS'. Primary outcome was a composite of all-cause death, heart failure hospitalisation and ventricular arrhythmia event. RESULTS: In total, 314 patients (61.3%) were classified as biopsy-proven CS, while 198 (38.7%) were classified as clinical CS. Patients classified under clinical CS were associated with higher prevalence of left ventricular dysfunction, septal thinning, and positive findings in fluorodeoxyglucose-positron emission tomography or Gallium scintigraphy than those under biopsy-proven CS. During median follow-up of 43.7 (23.3-77.3) months, risk of primary outcome was comparable between the groups (adjusted HR: 1.24, 95% CI: 0.88 to 1.75, p=0.22). Similarly, the risks of primary outcome were comparable between patients with clinical isolated CS who did not have other organ/tissue involvement, and biopsy-proven isolated CS (adjusted HR: 1.23, 95% CI: 0.56 to 2.70, p=0.61). CONCLUSIONS: A substantial number of patients were diagnosed with clinical CS without confirmatory biopsy. Considering the worse clinical outcomes irrespective of the histological evidence, the diagnosis of clinical CS is justifiable if imaging findings suggestive of CS are observed.


Asunto(s)
Cardiomiopatías , Miocarditis , Sarcoidosis , Humanos , Femenino , Persona de Mediana Edad , Anciano , Cardiomiopatías/diagnóstico , Sarcoidosis/diagnóstico , Sarcoidosis/epidemiología , Tomografía de Emisión de Positrones/métodos , Arritmias Cardíacas , Biopsia
20.
BMC Geriatr ; 22(1): 556, 2022 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-35787667

RESUMEN

BACKGROUND: The purpose of this study was to clarify the prevalence, association with frailty and exercise capacity, and prognostic implication of sarcopenic obesity in patients with heart failure. METHODS: The present study included 779 older adults hospitalized with heart failure (median age: 81 years; 57.4% men). Sarcopenia was diagnosed based on the guidelines by the Asian Working Group for Sarcopenia. Obesity was defined as the percentage of body fat mass (FM) obtained by bioelectrical impedance analysis. The FM cut-off points for obesity were 38% for women and 27% for men. The primary endpoint was 1-year all-cause death. We assessed the associations of sarcopenic obesity occurrence with the short physical performance battery (SPPB) score and 6-minute walk distance (6MWD). RESULTS: The rates of sarcopenia and obesity were 19.3 and 26.2%, respectively. The patients were classified into the following groups: non-sarcopenia/non-obesity (58.5%), non-sarcopenia/obesity (22.2%), sarcopenia/non-obesity (15.3%), and sarcopenia/obesity (4.0%). The sarcopenia/obesity group had a lower SPPB score and shorter 6MWD, which was independent of age and sex (coefficient, - 0.120; t-value, - 3.74; P < 0.001 and coefficient, - 77.42; t-value, - 3.61; P < 0.001; respectively). Ninety-six patients died during the 1-year follow-up period. In a Cox proportional hazard analysis, sarcopenia and obesity together were an independent prognostic factor even after adjusting for a coexisting prognostic factor (non-sarcopenia/non-obesity vs. sarcopenia/obesity: hazard ratio, 2.48; 95% confidence interval, 1.22-5.04; P = 0.012). CONCLUSION: Sarcopenic obesity is a risk factor for all-cause death and low physical function in older adults with heart failure. TRIAL REGISTRATION: University Hospital Information Network (UMIN-CTR: UMIN000023929 ).


Asunto(s)
Insuficiencia Cardíaca , Sarcopenia , Anciano , Anciano de 80 o más Años , Femenino , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/epidemiología , Humanos , Masculino , Obesidad/complicaciones , Obesidad/diagnóstico , Obesidad/epidemiología , Prevalencia , Factores de Riesgo , Sarcopenia/diagnóstico , Sarcopenia/epidemiología
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