RESUMEN
INTRODUCTION: High-power short-duration (HPSD) ablation at 50 W, guided by ablation index (AI) or lesion size index (LSI), and a 90 W/4 s very HSPD (vHPSD) setting are available for atrial fibrillation (AF) treatment. Yet, tissue temperatures during ablation with different catheters around venoatrial junction and collateral tissues remain unclear. METHODS: In this porcine study, we surgically implanted thermocouples on the epicardium near the superior vena cava (SVC), right pulmonary vein, and esophagus close to the inferior vena cava. We then compared tissue temperatures during 50W-HPSD guided by AI 400 or LSI 5.0, and 90 W/4 s-vHPSD ablation using THERMOCOOL SMARTTOUCH SF (STSF), TactiCath ablation catheter, sensor enabled (TacthCath), and QDOT MICRO (Qmode and Qmode+ settings) catheters. RESULTS: STSF produced the highest maximum tissue temperature (Tmax ), followed by TactiCath, and QDOT MICRO in Qmode and Qmode+ (62.7 ± 12.5°C, 58.0 ± 10.1°C, 50.0 ± 12.1°C, and 49.2 ± 8.4°C, respectively; p = .005), achieving effective transmural lesions. Time to lethal tissue temperature ≥50°C (t-T ≥ 50°C) was fastest in Qmode+, followed by TacthCath, STSF, and Qmode (4.3 ± 2.5, 6.4 ± 1.9, 7.1 ± 2.8, and 7.7 ± 3.1 s, respectively; p < .001). The catheter tip-to-thermocouple distance for lethal temperature (indicating lesion depth) from receiver operating characteristic curve analysis was deepest in STSF at 5.2 mm, followed by Qmode at 4.3 mm, Qmode+ at 3.1 mm, and TactiCath at 2.8 mm. Ablation at the SVC near the phrenic nerve led to sudden injury at t-T ≥ 50°C in all four settings. The esophageal adventitia injury was least deep with Qmode+ ablation (0.4 ± 0.1 vs. 0.8 ± 0.4 mm for Qmode, 0.9 ± 0.3 mm for TactiCath, and 1.1 ± 0.5 mm for STSF, respectively; p = .005), correlating with Tmax . CONCLUSION: This study revealed distinct tissue temperature patterns during HSPD and vHPSD ablations with the three catheters, affecting lesion effectiveness and collateral damage based on Tmax and/or t-T ≥ 50°C. These findings provide key insights into the safety and efficacy of AF ablation with these four settings.
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Fibrilación Atrial , Ablación por Catéter , Venas Pulmonares , Porcinos , Animales , Temperatura , Vena Cava Superior/cirugía , Catéteres , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/cirugía , Calor , Ablación por Catéter/efectos adversos , Venas Pulmonares/cirugía , Resultado del TratamientoRESUMEN
INTRODUCTION: Neither the actual in vivo tissue temperatures reached with 90 W/4 s-very high-power short-duration (vHPSD) ablation for atrial fibrillation nor the safety and efficacy profile have been fully elucidated. METHODS: We conducted a porcine study (n = 15) in which, after right thoracotomy, we implanted 6-8 thermocouples epicardially in the superior vena cava, right pulmonary vein, and esophagus close to the inferior vena cava. We compared tissue temperatures close to a QDOT MICRO catheter, between during 90 W/4 s-vHPSD ablation during ablation index (AI: target 400)-guided 50 W-HPSD ablation, both targeting a contact force of 8-15 g. RESULTS: Maximum tissue temperature reached during 90 W/4 s-vHPSD ablation did not differ significantly from that during 50 W-HPSD ablation (49.2 ± 8.4°C vs. 50.0 ± 12.1°C; p = .69) and correlated inversely with distance between the catheter tip and the thermocouple, regardless of the power settings (r = -0.52 and r = -0.37). Lethal temperature (≥50°C) was best predicted at a catheter tip-to-thermocouple distance cut-point of 3.13 and 4.27 mm, respectively. All lesions produced by 90 W/4 s-vHPSD or 50 W-HPSD ablation were transmural. Although there was no difference in the esophageal injury rate (50% vs. 66%, p = .80), the thermal lesion was significantly shallower with 90 W/4 s-vHPSD ablation than with 50W-HPSD ablation (381.3 ± 127.3 vs. 820.0 ± 426.1 µm from the esophageal adventitia; p = .039). CONCLUSION: Actual tissue temperatures reached with 90 W/4 s-vHPSD ablation appear similar to those with AI-guided 50 W-HPSD ablation, with the distance between the catheter tip and target tissue being shorter for the former. Although both ablation settings may create transmural lesions in thin atrial tissues, any resulting esophageal thermal lesions appear shallower with 90 W/4 s-vHPSD ablation.
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Fibrilación Atrial , Ablación por Catéter , Venas Pulmonares , Animales , Porcinos , Temperatura , Ablación por Catéter/efectos adversos , Ablación por Catéter/métodos , Vena Cava Superior , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/cirugía , Esófago/cirugía , Esófago/lesiones , Venas Pulmonares/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: Neither the actual in vivo tissue temperatures reached with lesion size index (LSI)-guided high-power short-duration (HPSD) ablation for atrial fibrillation nor the safety profile has been elucidated. METHODS: We conducted a porcine study (n = 7) in which, after right thoracotomy, we implanted 6-8 thermocouples epicardially in the superior vena cava, right pulmonary vein, and esophagus close to the inferior vena cava. We compared tissue temperatures reached during 50 W-HPSD ablation with those reached during standard (30 W) ablation, both targeting an LSI of 5.0 (5-15 g contact force). RESULTS: Tmax (maximum tissue temperature when the thermocouple was located ≤5 mm from the catheter tip) reached during HPSD ablation was modestly higher than that reached during standard ablation (58.0 ± 10.1°C vs. 53.6 ± 9.2°C; p = .14) and peak tissue temperature correlated inversely with the distance between the catheter tip and the thermocouple, regardless of the power settings (HPSD: r = -0.63; standard: r = -0.66). Lethal temperature (≥50°C) reached 6.3 ± 1.8 s and 16.9 ± 16.1 s after the start of HPSD and standard ablation, respectively (p = .002), and it was best predicted at a catheter tip-to-thermocouple distance cut point of 2.8 and 5.3 mm, respectively. All lesions produced by HPSD ablation and by standard ablation were transmural. There was no difference between HPSD ablation and standard ablation in the esophageal injury rate (70% vs. 75%, p = .81), but the maximum distance from the esophageal adventitia to the injury site tended to be shorter (0.94 ± 0.29 mm vs. 1.40 ± 0.57 mm, respectively; p = .09). CONCLUSIONS: Actual tissue temperatures reached with LSI-guided HPSD ablation appear to be modestly higher, with a shorter distance between the catheter tip and thermocouple achieving lethal temperature, than those reached with standard ablation. HPSD ablation lasting <6 s may help minimize lethal thermal injury to the esophagus lying at a close distance.
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Fibrilación Atrial , Ablación por Catéter , Venas Pulmonares , Porcinos , Animales , Temperatura , Vena Cava Superior , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/cirugía , Esófago/cirugía , Esófago/lesiones , Catéteres , Ablación por Catéter/efectos adversos , Venas Pulmonares/cirugía , Resultado del TratamientoRESUMEN
Extremely low alanine aminotransferase (ALT) may reflect aging, frailty, sarcopenia, and malnutrition in several cardiovascular diseases, but the association between low ALT and patient characteristics, cardiovascular and all-cause mortality is not well investigated in the population with atrial fibrillation. We conducted a post hoc analysis of a prospective, observational multicenter study. Patients with nonvalvular AF in the SAKURA AF Registry (n = 3156) were classified into 3 tertiles according to baseline ALT: first (ALT ≤ 15 U/L, n = 1098), second (15 < ALT < 23 U/L, n = 1055), and third (ALT ≥ 23 U/L, n = 1003). The first tertile had an older age; lower body mass index (BMI); higher prevalence of heart failure; and lower hemoglobin, total cholesterol, and triglycerides (all P < 0.05). During median 39.2 months follow-up, the first tertile had significantly higher incidences of cardiovascular and all-cause mortality (log-rank P < 0.001). Lower ALT was significantly associated with the incidence of cardiovascular and all-cause mortality, even after adjusting for clinically relevant factors (P < 0.05). Low ALT may reflect aging, sarcopenia, and malnutrition and be independently associated with a high risk of all-cause mortality in patients with AF.
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Fibrilación Atrial , Desnutrición , Sarcopenia , Alanina Transaminasa , Humanos , Estudios Prospectivos , Factores de RiesgoRESUMEN
AIMS: Multi-organ dysfunction was recently reported to be a common condition in patients with heart failure (HF). The Model for End-stage Liver Disease eXcluding International normalized ratio (MELD-XI) score reflects liver and kidney function. The prognostic relevance of this score has been reported in patients with a variety of cardiovascular diseases who are undergoing interventional therapies. However, the relationship between the severity of hepatorenal dysfunction assessed by the MELD-XI score and the long-term clinical outcomes of HF patients receiving cardiac resynchronization therapy (CRT) has not been evaluated. METHODS AND RESULTS: Clinical records of 283 patients who underwent CRT implantation between March 2003 and October 2020 were retrospectively evaluated (mean age 67 ± 12, 22.6% female). Blood samples were collected before CRT implantation. Patients were divided into three groups based on tertiles of the MELD-XI score: first tertile (MELD-XI = 9.44, n = 95), second tertile (9.44 < MELD-XI < 13.4, n = 94), and third tertile (MELD-XI ≥ 13.4, n = 94). The primary endpoint was all-cause mortality. Compared with the other groups, the third tertile group exhibited significantly older age, higher prevalence of diabetes mellitus and hypertension, lower haemoglobin level, and higher N-terminal pro-brain natriuretic peptide level (all P < 0.05). The functional CRT response rate was also significantly lower in the third tertile group (P = 0.011). During a median follow-up of 30 months (inter-quartile range, 9-67), 105 patients (37.1%) died. Kaplan-Meier analysis revealed that patients with a higher MELD-XI score had a greater risk of all-cause mortality (log-rank test: P < 0.001). Even after adjustment for clinically relevant factors and a conventional risk score, the MELD-XI score was still associated with mortality (adjusted hazard ratio: 1.04, 95% confidence interval: 1.00-1.07, P = 0.014, and adjusted hazard ratio: 1.04, 95% confidence interval: 1.01-1.09, P = 0.005, respectively). A higher MELD-XI score was associated with a greater risk of all-cause mortality than a lower MELD-XI score regardless of whether a pacemaker or defibrillator was implanted (log-rank test: P = 0.010 and P < 0.001, respectively). CONCLUSIONS: Impaired hepatorenal function assessed by the MELD-XI score was associated with older age, higher prevalence of multiple co-morbidities, severity of HF, lower CRT response rates, and subsequent all-cause mortality in HF patients undergoing CRT implantation. These results suggest that the MELD-XI score can provide additional prognostic information and may be useful for improving risk stratification in this population.
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Terapia de Resincronización Cardíaca , Enfermedad Hepática en Estado Terminal , Enfermedad Hepática en Estado Terminal/terapia , Femenino , Humanos , Masculino , Pronóstico , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
Despite emerging recognition of interactions between heart failure (HF) and liver dysfunction, the impact of cardiac hepatopathy on patients with HF undergoing cardiac resynchronization therapy (CRT) has not been fully elucidated. Albumin-bilirubin (ALBI) score is a new assessment of liver function. The relationship between liver dysfunction severity based on ALBI score and clinical outcomes of patients with HF receiving CRT is unclear. Clinical records of 274 patients who underwent CRT device implantation between March 2003 and October 2020 were retrospectively investigated. ALBI score was calculated based on serum albumin and total bilirubin levels obtained before CRT device implantation. Patients were divided into three groups based on ALBI score: first tertile (ALBI ≤ - 2.62, n = 91)), second tertile (- 2.62 < ALBI < - 2.13, n = 92), and third tertile (ALBI ≥ - 2.13, n = 91). The study endpoint was all-cause mortality. The third tertile group had more advanced NYHA functional class, lower hemoglobin levels, and higher total bilirubin, aspartate aminotransferase, γ-glutamyl transferase, and N-terminal Pro-B-type natriuretic peptide levels (all p < 0.05). The third tertile group also had a higher prevalence of moderate or severe tricuspid regurgitation and higher tricuspid regurgitation pressure gradient (all p < 0.05). CRT response rates were significantly lower in the third tertile group. During a median (interquartile range) follow-up of 30 (9-60) months, 104 (37.9%) patients died. The third tertile group had significantly higher rates of all-cause mortality (log-rank p < 0.001). Higher ALBI score was significantly associated with all-cause mortality, even after adjusting for clinically relevant factors, a conventional validated risk score, and echocardiographic parameters related to right HF (all p < 0.01). Higher ALBI score before CRT device implantation is associated with HF severity, hepatic congestion and impairment due to right HF, lower CRT response, and higher all-cause mortality in CRT recipients.
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Terapia de Resincronización Cardíaca , Insuficiencia Cardíaca , Insuficiencia de la Válvula Tricúspide , Bilirrubina , Terapia de Resincronización Cardíaca/efectos adversos , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/terapia , Humanos , Pronóstico , Estudios Retrospectivos , Albúmina Sérica , Insuficiencia de la Válvula Tricúspide/complicacionesRESUMEN
BACKGROUND: Actual in vivo tissue temperatures and the safety profile during high-power short-duration (HPSD) ablation of atrial fibrillation have not been clarified. METHODS: We conducted an animal study in which, after a right thoracotomy, we implanted 6-8 thermocouples epicardially in the superior vena cava, right pulmonary vein, and esophagus close to the inferior vena cava. We recorded tissue temperatures during a 50 W-HPSD ablation and 30 W-standard ablation targeting an ablation index (AI) of 400 (5-15 g contact force). RESULTS: Maximum tissue temperatures reached with HSPD ablation were significantly higher than that reached with standard ablation (62.7 ± 12.5 vs. 52.7 ± 11.4°C, p = 0.033) and correlated inversely with the distance between the catheter tip and thermocouple, regardless of the power settings (HPSD: r = -0.71; standard: r = -0.64). Achievement of lethal temperatures (≥50°C) was within 7.6 ± 3.6 and 12.1 ± 4.1 s after HPSD and standard ablation, respectively (p = 0.003), and was best predicted at cutoff points of 5.2 and 4.4 mm, respectively. All HPSD ablation lesions were transmural, but 19.2% of the standard ablation lesions were not (p = 0.011). There was no difference between HPSD and standard ablation regarding the esophageal injury rate (30% vs. 33.3%, p > 0.99), with the injury appearing to be related to the short distance from the catheter tip. CONCLUSIONS: Actual tissue temperatures reached with AI-guided HPSD ablation appeared to be higher with a greater distance between the catheter tip and target tissue than those with standard ablation. HPSD ablation for <7 s may help prevent collateral tissue injury when ablating within a close distance.
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Fibrilación Atrial , Ablación por Catéter , Venas Pulmonares , Animales , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/cirugía , Ablación por Catéter/efectos adversos , Venas Pulmonares/cirugía , Temperatura , Resultado del Tratamiento , Vena Cava Superior/cirugíaRESUMEN
AIMS: Malnutrition is common and associated with worse clinical outcomes in patients with heart failure (HF). The Controlling Nutritional Status (CONUT) score is an integrated index for evaluating diverse aspects of the complex mechanism of malnutrition. However, the relationship between the severity of malnutrition assessed by the CONUT score and clinical outcomes of HF patients receiving cardiac resynchronisation therapy (CRT) has not been fully clarified. METHODS: Clinical records of 263 patients who underwent pacemaker or defibrillator implantation for CRT between March 2003 and October 2020 were retrospectively evaluated. The CONUT score was calculated from laboratory data obtained before CRT device implantation. Patients were divided into three groups: normal nutrition (CONUT scores 0-1, n=58), mild malnutrition (CONUT scores 2-4, n=132) and moderate or severe malnutrition (CONUT scores 5-12, n=73). The primary endpoint was all-cause mortality. RESULTS: The moderate or severe malnutrition group had a lower body mass index, more advanced New York Heart Association functional class, higher Clinical Frailty Scale score, lower levels of haemoglobin and higher levels of N-terminal probrain natriuretic peptide (all p<0.05). In the moderate or severe malnutrition group, the CRT response rate was significantly lower than for the other two groups (p=0.001). During a median follow-up period of 31 (10-67) months, 103 (39.1%) patients died. Kaplan-Meier analysis revealed that the moderate or severe malnutrition group had a significantly higher mortality rate (log-rank p<0.001). A higher CONUT score and CONUT score ≥5 remained significantly associated with all-cause mortality after adjusting for previously reported clinically relevant factors and the conventional risk score (VALID-CRT risk score) (all p<0.05). CONCLUSIONS: A higher CONUT score before CRT device implantation was strongly associated with HF severity, frailty, lower CRT response rate and subsequent long-term all-cause mortality.
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Terapia de Resincronización Cardíaca , Insuficiencia Cardíaca/terapia , Desnutrición/terapia , Evaluación Nutricional , Estado Nutricional , Anciano , Causas de Muerte/tendencias , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/epidemiología , Humanos , Incidencia , Japón/epidemiología , Masculino , Desnutrición/etiología , Desnutrición/mortalidad , Persona de Mediana Edad , Pronóstico , Estudios RetrospectivosRESUMEN
AIMS: The prognostic value of genetic variants for predicting lethal arrhythmic events (LAEs) in Brugada syndrome (BrS) remains controversial. We investigated whether the functional curation of SCN5A variations improves prognostic predictability. METHODS AND RESULTS: Using a heterologous expression system and whole-cell patch clamping, we functionally characterized 22 variants of unknown significance (VUSs) among 55 SCN5A mutations previously curated using in silico prediction algorithms in the Japanese BrS registry (n = 415). According to the loss-of-function (LOF) properties, SCN5A mutation carriers (n = 60) were divided into two groups: LOF-SCN5A mutations and non-LOF SCN5A variations. Functionally proven LOF-SCN5A mutation carriers (n = 45) showed significantly severer electrocardiographic conduction abnormalities and worse prognosis associated with earlier manifestations of LAEs (7.9%/year) than in silico algorithm-predicted SCN5A carriers (5.1%/year) or all BrS probands (2.5%/year). Notably, non-LOF SCN5A variation carriers (n = 15) exhibited no LAEs during the follow-up period. Multivariate analysis demonstrated that only LOF-SCN5A mutations and a history of aborted cardiac arrest were significant predictors of LAEs. Gene-based association studies using whole-exome sequencing data on another independent SCN5A mutation-negative BrS cohort (n = 288) showed no significant enrichment of rare variants in 16 985 genes including 22 non-SCN5A BrS-associated genes as compared with controls (n = 372). Furthermore, rare variations of non-SCN5A BrS-associated genes did not affect LAE-free survival curves. CONCLUSION: In vitro functional validation is key to classifying the pathogenicity of SCN5A VUSs and for risk stratification of genetic predictors of LAEs. Functionally proven LOF-SCN5A mutations are genetic burdens of sudden death in BrS, but evidence for other BrS-associated genes is elusive.
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Síndrome de Brugada , Síndrome de Brugada/genética , Humanos , Mutación/genética , Canal de Sodio Activado por Voltaje NAV1.5/genética , Fenotipo , VirulenciaRESUMEN
BACKGROUND: A novel steerable sheath visualized on a three-dimensional mapping system has become available in this era in which a durable pulmonary vein (PV) isolation (PVI) with reduced fluoroscopy is required. METHODS: In 60 patients who underwent a PVI with a visualized sheath (n = 30) and non-visualized conventional sheath (n = 30), the fluoroscopic time and catheter stability during the PVI were analyzed. RESULTS: The fluoroscopic time during the transseptal access (0 [0, 0.1] vs. 1.4 [0.8, 2.3] minutes, P < .001) and PVI (0 [0, 0.1] vs. 0.4 [0.2, 1.1] minutes, P < .001) were shorter in the visualized sheath group than conventional sheath group. The procedure time during the PVI (32.0 [26.8, 36.3] vs. 41.0 [31.8, 47.3] minutes, P = .01), particularly during the right PVI (15.0 [12.8, 18.0] vs. 23.0 [15.8, 26.3] minutes, P = .009), was shorter in the visualized sheath group than conventional sheath group, however, that during the other steps was equivalent. The standard deviation of the catheter contact force during each radiofrequency application was smaller in the visualized sheath group than conventional sheath group (4.5 ± 2.7 vs. 4.9 ± 3.1 g, P = .001). The impedance drop for each lesion was larger in the visualized sheath group than conventional sheath group (10.7 ± 6.5 vs. 9.8 ± 5.5 ohms, P < .001). The incidence of acute PV reconnections per patient (30% vs. 23%, P = .56) and per PV segment (2.5% vs. 2.3%, P = .83) were similar between the two groups. No major complications occurred in either sheath group. CONCLUSIONS: The use of visualized sheaths may reduce the fluoroscopic time and improve the catheter stability during the PVI.
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Fibrilación Atrial/cirugía , Ablación por Catéter , Imagenología Tridimensional , Venas Pulmonares/cirugía , Ultrasonografía Intervencional , Anciano , Fibrilación Atrial/diagnóstico por imagen , Mapeo Epicárdico , Femenino , Fluoroscopía , Humanos , Masculino , Persona de Mediana Edad , Venas Pulmonares/diagnóstico por imagen , Factores de TiempoRESUMEN
BACKGROUND: The definition of response to cardiac resynchronization therapy (CRT) varies across clinical trials. There are two main definitions, i.e., echocardiographic response and functional response. We assessed which definition was more reasonable. METHODS: In this study of 260 patients who had undergone CRT, an echocardiographic response was defined as a reduction in a left ventricular end-systolic volume of greater than or equal to 15% or an improvement in left ventricular ejection fraction of greater than or equal to 5%. A functional response was defined as an improvement of at least one class category in the New York Heart Association functional classification. We assessed the response to CRT at 6 months after device implantation, based on each definition, and investigated the relationship between response and clinical outcomes. RESULTS: The echocardiographic response rate was 74.2%. The functional response rate was 86.9%. Non-responder status, based on both definitions, was associated with higher all-cause mortality. Cardiac death was only associated with functional non-responder status (hazard ratio (HR) 2.65, 95% confidence interval (CI) 1.19-5.46, p = 0.0186) and heart failure hospitalization (HR 2.78, 95% CI, 1.29-5.26, p = 0.0111). CONCLUSION: After CRT implantation, the functional response definition of CRT response is associated with a higher response rate and better clinical outcomes than that of the echocardiographic response definition, and therefore it is reasonable to use the functional definition to assess CRT response.
RESUMEN
BACKGROUND: How obesity and epicardial fat influence atrial fibrillation (AF) is unknown. METHODS: To investigate the effect of obesity/epicardial fat on the AF substrate, we divided 20 beagle dogs of normal weight into four groups (n = 5 each): one of the four groups (Obese-rapid atrial pacing [RAP] group) served as a novel canine model of obesity and AF. The other three groups comprised dogs fed a standard diet without RAP (Control group), dogs fed a high-fat diet without RAP (Obese group), or dogs fed a standard diet with RAP (RAP group). All underwent electrophysiology study, and hearts were excised for histopathologic and fibrosis-related gene expression analyses. RESULTS: Left atrial (LA) pressure was significantly higher in the Obese group than in the Control, RAP, and Obese-RAP groups (23.4 ± 6.9 vs. 11.4 ± 2.1, 11.9 ± 6.4, and 13.5 ± 2.9 mmHg; p = .005). The effective refractory period of the inferior PV was significantly shorter in the RAP and Obese-RAP groups than in the Control group (p = .043). Short-duration AF was induced at greatest frequency in the Obese-RAP and Obese groups (p < .05). Epicardial fat/Fatty infiltration was greatest in the Obese-RAP group, and greater in the Obese and RAP groups than in the Control group. %interstitial fibrosis/fibrosis-related gene expression was significantly greater in the Obese-RAP and RAP groups (p < .05). CONCLUSIONS: Vulnerability to AF was associated with increased LA pressure and increased epicardial fat/fatty infiltration in our Obese group, and with increased epicardial fat/fibrofatty infiltration in the RAP and Obese-RAP groups. These may explain the role of obesity/epicardial fat in the pathogenesis of AF.
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Fibrilación Atrial , Remodelación Atrial , Tejido Adiposo , Animales , Fibrilación Atrial/etiología , Modelos Animales de Enfermedad , Perros , Atrios Cardíacos , Obesidad/complicaciones , PericardioRESUMEN
BACKGROUND: Mutations in the nuclear envelope genes encoding LMNA and EMD are responsible for Emery-Dreifuss muscular dystrophy. However, LMNA mutations often manifest dilated cardiomyopathy with conduction disturbance without obvious skeletal myopathic complications. On the contrary, the phenotypic spectrums of EMD mutations are less clear. Our aims were to determine the prevalence of nonsyndromic forms of emerinopathy, which may underlie genetically undefined isolated cardiac conduction disturbance, and the etiology of thromboembolic complications associated with EMD mutations. METHODS: Targeted exon sequencing was performed in 87 probands with familial sick sinus syndrome (n=36) and a progressive cardiac conduction defect (n=51). RESULTS: We identified 3 X-linked recessive EMD mutations (start-loss, splicing, missense) in families with cardiac conduction disease. All 3 probands shared a common clinical phenotype of progressive atrial arrhythmias that ultimately resulted in atrial standstill associated with left ventricular noncompaction (LVNC), but they lacked early contractures and progressive muscle wasting and weakness characteristic of Emery-Dreifuss muscular dystrophy. Because the association of LVNC with EMD has never been reported, we further genetically screened 102 LVNC patients and found a frameshift EMD mutation in a boy with progressive atrial standstill and LVNC without complications of muscular dystrophy. All 6 male EMD mutation carriers of 4 families underwent pacemaker or defibrillator implantation, whereas 2 female carriers were asymptomatic. Notably, a strong family history of stroke observed in these families was probably due to the increased risk of thromboembolism attributable to both atrial standstill and LVNC. CONCLUSIONS: Cardiac emerinopathy is a novel nonsyndromic X-linked progressive atrial standstill associated with LVNC and increased risk of thromboembolism.
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Cardiomiopatías/genética , Enfermedades Genéticas Congénitas/genética , Atrios Cardíacos/anomalías , Bloqueo Cardíaco/genética , No Compactación Aislada del Miocardio Ventricular/genética , Proteínas de la Membrana/genética , Mutación , Proteínas Nucleares/genética , Accidente Cerebrovascular/etiología , Tromboembolia/etiología , Distrofia Muscular de Emery-Dreifuss Ligada a X/genética , Adolescente , Adulto , Anciano , Trastorno del Sistema de Conducción Cardíaco/complicaciones , Trastorno del Sistema de Conducción Cardíaco/diagnóstico , Trastorno del Sistema de Conducción Cardíaco/genética , Cardiomiopatías/complicaciones , Cardiomiopatías/diagnóstico , Niño , Femenino , Enfermedades Genéticas Congénitas/complicaciones , Enfermedades Genéticas Congénitas/diagnóstico , Predisposición Genética a la Enfermedad , Bloqueo Cardíaco/complicaciones , Bloqueo Cardíaco/diagnóstico , Humanos , No Compactación Aislada del Miocardio Ventricular/complicaciones , No Compactación Aislada del Miocardio Ventricular/diagnóstico , Masculino , Persona de Mediana Edad , Fenotipo , Síndrome del Seno Enfermo/complicaciones , Síndrome del Seno Enfermo/genética , Accidente Cerebrovascular/diagnóstico por imagen , Tromboembolia/diagnóstico por imagen , Distrofia Muscular de Emery-Dreifuss Ligada a X/complicaciones , Distrofia Muscular de Emery-Dreifuss Ligada a X/diagnóstico , Adulto JovenRESUMEN
Rate-responsive pacing is known to improve quality of life (QOL) in patients with sick sinus syndrome and chronotropic incompetence. However, the sensors for rate response include accelerometers, closed-loop stimulation (CLS), and minute ventilation sensors (MV sensors), each of which has a different mode of action. For this reason, it is important to select appropriate sensors that match the daily habits and behavioral patterns of the patient. For example, young and active patients are expected to have a rate increase when an accelerometer is used, while elderly patients and patients with a physical disability who are only able to move slowly often have a poor response to the accelerometer. MV sensors are therefore better suited to these patients. Furthermore, CLS is considered effective for patients who require an increase in heart rate when at rest, for example, patients undergoing maintenance dialysis.We describe a representative case, demonstrating the effectiveness of closed-loop stimulation in a patient with hypotension during dialysis.
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Terapia de Resincronización Cardíaca/métodos , Diálisis Renal , Síndrome del Seno Enfermo/terapia , Anciano , Humanos , MasculinoRESUMEN
Atrial fibrillation (AF) and heart failure (HF) often coexist. The aims of this study were to explore the factors associated with the serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), and the association between prognosis and a history of HF or the serum NT-proBNP level in Japanese patients with AF.The present sub-study was based on the SAKURA AF Registry, a Japanese multicenter observational registry that included 3267 AF patients (median follow-up period: 39 months). All the patients were receiving warfarin or any of four direct oral anticoagulants. Serum NT-proBNP levels were available for 2417 patients, and the median value was 508 (interquartile range 202-1095) pg/mL at the time of enrollment. Log NT-proBNP was associated with non-paroxysmal AF, creatinine clearance > 60 mL/minute, history of HF and ischemic heart disease, antiarrhythmic drug use, anemia, being elderly female, and history of AF ablation. The relative risk of adverse clinical events, except major bleeding, was significantly higher in the highest NT-proBNP quartile as compared to the lowest quartile (adjusted hazard ratios: 2.87 for death, 2.39 for stroke), but a history of HF was associated only with a higher incidence of all-cause death.Concomitant HF was associated with a higher mortality, but the high NT-proBNP was associated with higher mortality and stroke events. In Japanese AF patients receiving anticoagulant treatment, high serum NT-proBNP levels predict the risk for both stroke events and deaths, and intensive follow-up is needed in such patients.
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Fibrilación Atrial/complicaciones , Insuficiencia Cardíaca/complicaciones , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Sistema de Registros , Accidente Cerebrovascular/etiología , Anciano , Anciano de 80 o más Años , Anticoagulantes/uso terapéutico , Fibrilación Atrial/sangre , Fibrilación Atrial/mortalidad , Femenino , Insuficiencia Cardíaca/mortalidad , Humanos , Japón/epidemiología , Masculino , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/prevención & controlRESUMEN
Desmin-related myopathy (DRM) is a rare heritable cardiac and skeletal muscle disease caused by mutations in the desmin gene (DES). DRM is generally characterized by skeletal muscle weakness, conduction disturbance, and dilated cardiomyopathy. However, the clinical cardiac phenotypes of DRM are not yet fully understood. Herein, we report the first case of DRM with the de novo missense DES mutation, R454W, that is characterized by left ventricular non-compaction cardiomyopathy, progressive cardiac conduction defect, spontaneous coronary artery dissection, and no skeletal muscle weakness. Our case findings suggest that clinicians should genetically test patients who have cardiomyopathy, progressive cardiac conduction defect, and coronary artery dissection, even if the patient has neither family history of DRM nor skeletal muscle symptoms.
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Cardiomiopatías , Vasos Coronarios , Desmina/genética , Disección , Bloqueo Cardíaco , Humanos , Distrofias Musculares , LinajeRESUMEN
BACKGROUND: The burden or benefit of anticoagulation treatment affects patient satisfaction, which may in turn affect the adherence to the treatment and subsequent outcomes. Thus, we hypothesized that the patient satisfaction with direct oral anticoagulants (DOACs) may influence the clinical outcome in patients with atrial fibrillation (AF). METHODS AND RESULTS: We investigated the clinical outcomes among 719 DOAC users (age 71.9 ± 9.1 years, 184 females, and 449 persistent AF) enrolled in the SAKURA AF Registry who completed a satisfaction questionnaire with anticoagulation therapy by means of the Anti-Clot Treatment Scale (ACTS), which included 12-item burden and 3-item benefit scales. During a 41.8-month-follow-up, a stroke/systemic embolism (SE) occurred in 27 patients (3.8%) and major bleeding events in 25 (3.5%). A univariate Cox regression analysis revealed that an older age, persistent AF, higher CHA2DS2-VASc score, no history of AF ablation, lower creatinine clearance, and lower ACTS benefit scores were significantly associated with an increased risk of a stroke/SE, but not with major bleeding events. A low benefit score remained an independent predictor of a stroke/SE even after a multivariate adjustment. The ACTS burden scores were not associated with any clinical events. CONCLUSIONS: We found a strong association between a low benefit satisfaction and increased stroke risk. We should follow patients carefully to educate them on treatment importance for patients unsatisfied with the benefits of DOACs for stroke prevention.
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Anticoagulantes/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Satisfacción del Paciente , Administración Oral , Anciano , Anciano de 80 o más Años , Femenino , Hemorragia/inducido químicamente , Humanos , Japón , Masculino , Persona de Mediana Edad , Sistema de Registros , Accidente Cerebrovascular/prevención & controlRESUMEN
BACKGROUND: Liver diseases drive the development and progression of atrial fibrillation (AF). The Fibrosis-4 (FIB4) index is a non-invasive scoring method for detecting liver fibrosis, but the prognostic impact of using it for AF patients is still unknown. Herein, we evaluated using the FIB4 index as a risk assessment tool for cardiovascular events and mortality in patients with AF. METHODS: We performed a post-hoc analysis of a prospective, observational multicenter study. A total of 3067 patients enrolled in a multicenter Japanese registry were grouped as first tertile (FIB4 index < 1.75, n = 1022), second tertile (1.75 ≤ FIB4 index < 2.51, n = 1022), and third tertile (FIB4 index ≥ 2.51, n = 1023). RESULTS: The third tertile had statistically significant results: older age, lower body mass index, increased heart failure prevalence, and lower clearances of hemoglobin and creatinine (all p < 0.05). During the follow-up period, incidences of major bleeding, cardiovascular events, and all-cause mortality were significantly higher for the third tertile (all p < 0.05). After multivariate adjustment, the third tertile associated independently with cardiovascular events (HR 1.72; 95% CI 1.31-2.25) and all-cause mortality (HR 1.43; 95% CI 1.06-1.95). Adding the FIB4 index to a baseline model with CHA2DS2-VASc score improved the prediction of cardiovascular events and all-cause mortality, as shown by the significant increase in the C-statistic (all p < 0.05), net reclassification improvement (all p < 0.001), and integrated discrimination improvement (all p < 0.001). A FIB4 index ≥ 2.51 most strongly associated with cardiovascular events and all-cause mortality in AF patients with high CHADS2 scores (all p < 0.001). CONCLUSIONS: The FIB4 index is independently associated with risks of cardiovascular events and all-cause mortality in AF patients.
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A prolonged QRS duration (QRSd) is promising for a response to cardiac resynchronization therapy (CRT). The variation in human body sizes may affect the QRSd. We hypothesized that conduction disturbances may exist in Japanese even with a narrow (< 130 ms)-QRS complex; such patients could be CRT candidates. We investigated the relationships between QRSd and sex and body size in Japanese. We retrospectively analyzed the values of 338 patients without heart failure (HF) (controls) and 199 CRT patients: 12-lead electrocardiographically determined QRSd, left ventricular diastolic and systolic diameters (LVDd and LVDs), body surface area (BSA), body mass index (BMI), and LVEF. We investigated the relationships between the QRSd and BSA, BMI, and LVD. The men's and women's BSA values were 1.74 m2 and 1.48 m2 in the controls (p < 0.0001), and 1.70 m2 and 1.41 m2 in the CRT patients (p < 0.0001). The men's and women's QRSd values were 96.1 ms and 87.4 ms in the controls (p < 0.0001), and 147.8 ms and 143.9 ms in the CRT group (p = 0.4633). In the controls, all body size and LVD variables were positively associated with QRSd. The CRT response rate did not differ significantly among narrow-, mid-, and wide-QRS groups (83.6%, 91.3%, 92.4%). An analysis of the ROC curve provided a QRS cutoff value of 114 ms for CRT responder. The QRSd appears to depend somewhat on body size in patients without HF. The CRT response rate was better than reported values even in patients with a narrow QRSd (< 130 ms). When patients are considered for CRT, a QRSd > 130 ms may not be necessary, and the current JCS guidelines appear to be appropriate.
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Potenciales de Acción , Arritmias Cardíacas/terapia , Índice de Masa Corporal , Superficie Corporal , Terapia de Resincronización Cardíaca , Sistema de Conducción Cardíaco/fisiopatología , Insuficiencia Cardíaca/terapia , Frecuencia Cardíaca , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/fisiopatología , Terapia de Resincronización Cardíaca/efectos adversos , Toma de Decisiones Clínicas , Femenino , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/fisiopatología , Humanos , Japón , Masculino , Persona de Mediana Edad , Selección de Paciente , Estudios Retrospectivos , Factores Sexuales , Volumen Sistólico , Resultado del Tratamiento , Función Ventricular Izquierda , Adulto JovenRESUMEN
BACKGROUND: Relations between characteristics and outcomes of patients in Japan with atrial fibrillation (AF) and the type of medical facility providing their outpatient care are unclear. METHODS AND RESULTS: We compared patient characteristics and outcomes between 2 university hospitals (n=1178), 20 general hospitals (n=1308), and 41 private clinics (n=751) (follow-up: 39.3 months) in the prospective SAKURA AF Registry. Private clinic patients were significantly older than university hospital and general hospital patients (73.4±9.2 vs. 70.3±9.8 and 72.6±8.9 years; p<0.001), and these patients' CHADS2 scores were significantly lower than general hospital, but higher than university hospital patients (1.8±1.1 vs. 2.0±1.2 and 1.6±1.1; p<0.001). The Kaplan-Meier incidences of stroke/systemic embolism (SE) (1.72 vs. 1.58 vs. 0.84 events per 100 patient-years; p=0.120), a cardiovascular event (4.09 vs. 2.44 vs. 1.40; p<0.001), and death were higher (2.39 vs. 2.21 vs. 1.24; p=0.015) for university and general hospital patients than for private clinic patients; the incidences of major bleeding were equivalent (1.78 vs. 1.33 vs. 1.16; p=0.273). After multivariate adjustments, this trend persisted. CONCLUSIONS: Adverse clinical events at small to large hospitals appear to be higher than those at private clinics, suggesting that careful attention for preventing stroke/SE and cardiovascular events should be paid to patients at a university or general hospital.