RESUMEN
BACKGROUND: Idiopathic atypical (non-cavotricuspid isthmus-dependent) atrial flutter (IAAFL) may be seen in patients without structural heart disease and without previous cardiac surgery or ablation. OBJECTIVE: This study sought to determine the patient characteristics, electrophysiologic and electroanatomic properties, and clinical outcomes after ablation in patients with IAAFL. METHODS: We retrospectively compared IAAFL patients with cavotricuspid isthmus-dependent AFL (C-AFL) patients undergoing catheter ablation. The primary outcome was a composite of death from cardiovascular causes, ischemic stroke, and hospitalization for worsening of heart failure. RESULTS: Of 180 patients who underwent catheter ablation for AFL, 89 were included in this study (22 IAAFL and 67 C-AFL). Electrophysiologic study showed significantly longer intra-atrial conduction time and lower atrial voltage during sinus rhythm in the IAAFL group compared with the C-AFL group. The atrial scar was observed in all 22 IAAFL patients, with the most common sites being the posterior or lateral wall of the right atrium in 10 (45.5%) and the anterior wall of the left atrium in 8 (36.4%). During 3.5 ± 2.8 years of follow-up, the composite primary end point occurred significantly more frequently in the IAAFL group (hazard ratio [HR], 3.45; 95% confidence interval [CI], 1.20-9.89; P = .015). In multivariable analysis, brain natriuretic peptide levels (HR, 1.01; 95% CI, 1.00-1.01, per 1 pg/mL; P = .01) and IAAFL (HR, 4.14; 95% CI, 1.21-14.07; P = .02) were independently associated with the primary outcome. CONCLUSION: IAAFL in patients had distinct electrophysiologic features suggestive of atrial cardiomyopathy. These patients are at risk for development of cardiovascular adverse events after ablation.
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BACKGROUND: Left atrial calcification (LAC) has occasionally been observed in patients who underwent catheter ablation for atrial fibrillation (AF) by chest computed tomography (CT). However, the evidence regarding the clinical impact of LAC in patients with AF is lacking. OBJECTIVES: This study aims to investigate the prevalence of LAC in AF patients and evaluate its clinical significance after AF ablation. METHODS: This observational registry included AF patients who received computed tomography and serial transthoracic echocardiography between January 2010 and November 2017. The primary composite outcome included cardiovascular death, hospitalization for worsening heart failure, and ischemic stroke. RESULTS: Among 534 patients (age 72 ± 13 years, 62.5% men) who met the inclusion criteria, 31 (5.8%) had LAC. In multivariable analysis, AF ablation was associated with an 11.8-fold (OR: 11.8; 95% CI: 2.03-227.65) increased risk of the development of LAC in AF patients. Among 218 patients with AF ablation, LAC was detected in 30 (13.8%) patients. Prior stroke (HR: 2.73; 95% CI: 1.08-6.93) and multiple ablation procedures (HR: 4.21; 95% CI: 1.63-10.87) were independently associated with the development of LAC in AF-ablation patients. During a median follow-up of 5.8 years, the primary composite outcome occurred in 11 patients in the LAC group (39.8 per 1,000 person-years) and 10 patients in the non-LAC group (8.9 per 1,000 person-years). The adjusted HR for the primary composite outcome in the LAC group, as compared with the non-LAC group, was 2.81 (95% CI: 1.16-6.84; P = 0.02). CONCLUSIONS: The presence of LAC was a significant and independent prognostic factor for identifying major adverse cardiovascular events after AF ablation.
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Fibrilación Atrial , Ablación por Catéter , Masculino , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Femenino , Fibrilación Atrial/epidemiología , Fibrilación Atrial/cirugía , Fibrilación Atrial/complicaciones , Pronóstico , Resultado del Tratamiento , Atrios Cardíacos , Ablación por Catéter/efectos adversos , Ablación por Catéter/métodosRESUMEN
Pulmonary regurgitation (PR) is a risk factor for sudden cardiac death in adult patients with repaired tetralogy of Fallot (TOF). However, transthoracic echocardiography (TTE) cannot fully visualize the pulmonary valve (PV) and PR. We investigated whether intracardiac echocardiography (ICE) could visualize the PV and PR better than TTE. Thirty adult patients with TOF (mean age 33 ± 15 years) scheduled for cardiac catheterization underwent ICE. The visualization of PV and the severity of PR were classified into three grades. ICE depicted the PV better than TTE (ICE vs. TTE: not visualized, partially visualized, and fully visualized: n = 1 [3%], n = 13 [43%], and n = 16 [53%] vs. n = 14 [47%], n = 13 [43%], and n = 3 [10%], p < 0.001). Especially in patients after pulmonary valve replacement (PVR), the PV was more fully visualized by ICE. The assessment of PR by TTE underestimated the severity of PR in comparison to cardiac magnetic resonance imaging (MRI) (severe PR: 8 [28%] vs. 22 [76%], p = 0.004), while there was no discrepancy between the results of ICE and MRI (21 [72%] vs. 22 [76%], p = 1.000). In comparison to TTE, ICE can safely provide better visualization of the PV and PR in adults with TOF, especially in patients who have undergone PVR.
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BACKGROUND: Dilated cardiomyopathy (DCM) is a life-threatening disease, resulting in refractory heart failure. An immune disorder underlies the pathophysiology associated with heart failure progression. Invariant natural killer T (iNKT) cell activation is a prospective therapeutic strategy for ischemic heart disease. However, its efficacy in nonischemic cardiomyopathy, such as DCM, remains to be elucidated, and the feasible modality for iNKT cell activation in humans is yet to be validated. METHODS: Dendritic cells isolated from human volunteers were pulsed with α-galactosylceramide ex vivo, which were used as α-galactosylceramide-pulsed dendritic cells (αGCDCs). We treated DCM mice harboring mutated troponin TΔK210/ΔK210 with αGCDCs and evaluated the efficacy of iNKT cell activation on heart failure in DCM mice. Furthermore, we investigated the molecular basis underlying its therapeutic effects in these mice and analyzed primary cardiac cells under iNKT cell-secreted cytokines. RESULTS: The number of iNKT cells in the spleens of DCM mice was reduced compared with that in wild-type mice, whereas αGCDC treatment activated iNKT cells, prolonged survival of DCM mice, and prevented decline in the left ventricular ejection fraction for 4 weeks, accompanied by suppressed interstitial fibrosis. Mechanistically, αGCDC treatment suppressed TGF (transforming growth factor)-ß signaling and expression of fibrotic genes and restored vasculature that was impaired in DCM hearts by upregulating angiopoietin 1 (Angpt1) expression. Consistently, IFNγ (interferon gamma) suppressed TGF-ß-induced Smad2/3 signaling and the expression of fibrotic genes in cardiac fibroblasts and upregulated Angpt1 expression in cardiomyocytes via Stat1. CONCLUSIONS: Immunomodulatory cell therapy with αGCDCs is a novel therapeutic strategy for heart failure in DCM.
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Cardiomiopatía Dilatada , Insuficiencia Cardíaca , Ratones , Humanos , Animales , Cardiomiopatía Dilatada/genética , Cardiomiopatía Dilatada/terapia , Cardiomiopatía Dilatada/metabolismo , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/terapia , Insuficiencia Cardíaca/metabolismo , Volumen Sistólico , Función Ventricular Izquierda , Fibrosis , Células Dendríticas/metabolismo , Tratamiento Basado en Trasplante de Células y TejidosRESUMEN
A 20-year-old man with arrhythmogenic right ventricular cardiomyopathy (ARVC) was resuscitated from ventricular fibrillation. He was transferred to our hospital because of progressive multiorgan dysfunction despite mechanical circulatory support with peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO) and intra-aortic balloon pump (IABP). At admission to our hospital, chest X-ray showed bilateral complete lung opacification, and echocardiography revealed a massive thrombus occupying the left atrium (LA) and left ventricle (LV). Conversion to central ECMO with transapical LV venting and thrombectomy were performed. The huge LA thrombus occluded all pulmonary veins (PVs). Despite the surgery and intensive care, complete lung opacity remained, and he died of multiorgan failure associated with sepsis. Autopsy demonstrated bilateral pulmonary multiple red infarctions, and histopathology showed alveolar wall necrosis with extensive hemorrhage, confirming a diagnosis of pulmonary hemorrhagic infarction. Extensive pulmonary infarction was attributable to PV occlusion due to massive LA thrombus. PV thrombosis should be considered when refractory lung opacities are encountered during VA-ECMO and necessitates early intervention.
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Displasia Ventricular Derecha Arritmogénica/complicaciones , Oxigenación por Membrana Extracorpórea/métodos , Insuficiencia Multiorgánica/complicaciones , Trombosis/diagnóstico , Fibrilación Ventricular/etiología , Autopsia/métodos , Ecocardiografía/métodos , Resultado Fatal , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/patología , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/patología , Hemorragia/complicaciones , Hemorragia/diagnóstico , Humanos , Contrapulsador Intraaórtico/métodos , Masculino , Infarto Pulmonar/diagnóstico , Venas Pulmonares/diagnóstico por imagen , Venas Pulmonares/patología , Enfermedad Veno-Oclusiva Pulmonar/complicaciones , Enfermedad Veno-Oclusiva Pulmonar/diagnóstico , Resucitación/métodos , Sepsis/complicaciones , Trombectomía/métodos , Trombosis/patología , Trombosis/cirugía , Fibrilación Ventricular/terapia , Adulto JovenRESUMEN
In the Fontan circulation, there is a substantial degree of systemic-to-pulmonary collateral flow (SPCF), which can be measured by cardiac magnetic resonance (CMR). However, the correlation between the degree of SPCF and long-term outcomes is not fully understood. We retrospectively studied 321 patients who underwent the Fontan procedure and CMR at a single center. Using CMR, we calculated SPCF as pulmonary blood flow - systemic blood flow. %SPCF was defined as SPCF ÷ pulmonary blood flow. The mean age of patients at CMR was 14.3 ± 7.5 years. The average %SPCF was 13.0% ± 11.0%. With a multivariate analysis, %SPCF was significantly correlated with time (i.e., the longer the time period since the Fontan procedure, the lower the %SPCF) (p = 0.006), previous total anomalous pulmonary vein drainage (p = 0.007), a low pulmonary artery index (Nakata index) before the Fontan procedure (p = 0.04), and older age at the time of the Fontan procedure (p = 0.002). Regarding the findings after the Fontan procedure, %SPCF was significantly correlated with ventricular end-diastolic volume (p < 0.001), ventricular end-systolic volume (p < 0.001), central venous pressure (p < 0.001), plasma brain natriuretic peptide concentration (p < 0.001), hemoptysis (p = 0.009), and poor New York Heart Association functional class (p = 0.007). SPCF was correlated with clinical condition after the Fontan procedure. The importance of sufficient growth of the pulmonary vascular bed should be emphasized because the development of SPCF is believed to result from the poor condition of the pulmonary circulation.
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Procedimiento de Fontan/métodos , Cardiopatías Congénitas/cirugía , Circulación Pulmonar , Adolescente , Velocidad del Flujo Sanguíneo , Niño , Femenino , Cardiopatías Congénitas/fisiopatología , Ventrículos Cardíacos/fisiopatología , Hemoptisis , Humanos , Imagen por Resonancia Magnética , Masculino , Análisis Multivariante , Arteria Pulmonar/fisiopatología , Estudios Retrospectivos , Volumen Sistólico , Adulto JovenRESUMEN
Mucolipidosis type III α/ß is an autosomal recessive lysosomal storage disease, caused by the deficient activity of UDP-N-acetyl glucosamine-1-phosphotransferase. The resultant intralysosomal accumulation of partly degraded mucopolysaccharides and sphingolipids causes multiple-organ damage, including the heart. The most documented cardiac manifestation is the thickening and insufficiency of mitral and aortic valves, but there are very few reports about the myocardial involvement. We report a case with mucolipidosis type III α/ß complicated by marked dilatation and dysfunction of the right ventricle, which is quite rare and further broadens the clinical spectrum of the disease.
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Insuficiencia de la Válvula Aórtica , Cardiomegalia , Diuréticos/administración & dosificación , Ventrículos Cardíacos , Insuficiencia de la Válvula Pulmonar , Disfunción Ventricular Derecha , Adulto , Insuficiencia de la Válvula Aórtica/diagnóstico por imagen , Insuficiencia de la Válvula Aórtica/etiología , Cardiomegalia/diagnóstico por imagen , Cardiomegalia/etiología , Dilatación Patológica , Ecocardiografía/métodos , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/patología , Ventrículos Cardíacos/fisiopatología , Humanos , Imagen por Resonancia Cinemagnética/métodos , Masculino , Mucolipidosis/diagnóstico , Tamaño de los Órganos , Manejo de Atención al Paciente/métodos , Insuficiencia de la Válvula Pulmonar/diagnóstico por imagen , Insuficiencia de la Válvula Pulmonar/etiología , Insuficiencia de la Válvula Pulmonar/fisiopatología , Disfunción Ventricular Derecha/diagnóstico , Disfunción Ventricular Derecha/etiología , Disfunción Ventricular Derecha/fisiopatología , Disfunción Ventricular Derecha/terapiaRESUMEN
BACKGROUND: An inverse relationship exists between hospital case volume and mortality in patients with heart failure (HF). However, hospital performance factors associated with mortality in HF patients have not been examined. We aimed to identify these using exploratory factor analysis and assess the relationship between these factors and 7-day, 30-day, and in-hospital mortality among HF patients in Japan.MethodsâandâResults:We analyzed the records of 198,861 patients admitted to 683 certified hospitals of the Japanese Circulation Society between 2012 and 2014. Records were obtained from the nationwide database of the Japanese Registry Of All cardiac and vascular Diseases-Diagnostic Procedure Combination (JROAD-DPC). Using exploratory factor analysis, 90 hospital survey items were grouped into 5 factors, according to their collinearity: "Interventional cardiology", "Cardiovascular surgery", "Pediatric cardiology", "Electrophysiology" and "Cardiac rehabilitation". Multivariable logistic regression analysis was performed to determine the association between these factors and mortality. The 30-day mortality was 8.0%. Multivariable logistic regression analysis showed the "Pediatric cardiology" (odds ratio (OR) 0.677, 95% confidence interval [CI]: 0.628-0.729, P<0.0001), "Electrophysiology" (OR 0.876, 95% CI: 0.832-0.923, P<0.0001), and "Cardiac rehabilitation" (OR 0.832, 95% CI: 0.792-0.873, P<0.0001) factors were associated with lower mortality. In contrast, "Interventional cardiology" (OR 1.167, 95% CI: 1.070-1.272, P<0.0001) was associated with higher mortality. CONCLUSIONS: Hospital factors, including various cardiovascular therapeutic practices, may be associated with the early death of HF patients.
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Insuficiencia Cardíaca/mortalidad , Mortalidad Hospitalaria , Hospitalización , Reclamos Administrativos en el Cuidado de la Salud , Anciano , Anciano de 80 o más Años , Análisis por Conglomerados , Bases de Datos Factuales , Análisis Factorial , Femenino , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/terapia , Humanos , Japón/epidemiología , Masculino , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
Takotsubo syndrome (TTS), also referred to as stress cardiomyopathy, is characterized by transient left ventricular apical ballooning in the absence of obstructive coronary artery disease. Catecholamine-induced cardiac injury or vasospasm has been implicated in this pathophysiology. We present a case of a 67-year-old man 10 years after heart transplantation diagnosed with TTS. Sympathetic reinnervation could not be detected by iodine-123 meta iodobenzylguanidine uptake, suggesting that TTS can occur in the absence of functional sympathetic nerve systems reconstruction.
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Trasplante de Corazón , Cardiomiopatía de Takotsubo , 3-Yodobencilguanidina , Anciano , Corazón , Trasplante de Corazón/efectos adversos , Humanos , Masculino , Sistema Nervioso Simpático , Cardiomiopatía de Takotsubo/diagnóstico , Cardiomiopatía de Takotsubo/etiologíaRESUMEN
A 44-year-old man was admitted to our hospital due to heart failure. Transthoracic echocardiography demonstrated global hypokinesis with an ejection fraction of 25%, prominent trabeculation and deep intertrabecular recesses, and apical aneurysm with multiple thrombi (10×13 mm in the inferior wall, 15×8 mm in the anterior wall). Cardiac magnetic resonance imaging showed an increased ratio of noncompacted (NC) to compacted (C) myocardium (NC/C ratio >2.3) and apical aneurysm. Coronary angiography revealed no significant stenosis. He was therefore diagnosed with left ventricular noncompaction complicated by apical aneurysm. Four weeks after starting anticoagulation, the multiple apical thrombi disappeared without clinical signs of embolism.
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Aneurisma/complicaciones , Aneurisma/tratamiento farmacológico , Anticoagulantes/uso terapéutico , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/tratamiento farmacológico , Ventrículos Cardíacos/fisiopatología , Trombosis/fisiopatología , Adulto , Aneurisma/diagnóstico por imagen , Aneurisma/fisiopatología , Angiografía Coronaria , Ecocardiografía , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/fisiopatología , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Trombosis/etiología , Resultado del TratamientoRESUMEN
Bradycardia is a common complication at the early postoperative period after heart transplantation (HT). The heart rate (HR) usually recovers within a few weeks; however, several patients need a temporary pacemaker or chronotropic agents to stabilize their hemodynamics. Here, we report the first case of transient bradycardia associated with hemodynamic deterioration following HT, which was successfully treated with cilostazol, a phosphodiesterase-3-inhibiting agent. A 59-year-old man received HT for advanced heart failure due to ischemic cardiomyopathy. General fatigue persisted even after the HT. His HR was around 60 beats per minute (bpm) with sinus rhythm. Echocardiography showed no abnormal findings. Right heart catheterization showed that the cardiac index (CI) was 1.9 L/minute/m2. Continuous intravenous infusion of isoproterenol (0.003 µg/kg/minute) increased the HR to 80 bpm and CI to 2.7 L/minute/m2 and improved his symptoms. Isoproterenol was switched to oral administration of cilostazol (100 mg, twice a day), which maintained the HR at around 80 bpm and CI of 2.5 L/minute/m2. The patient's HR gradually recovered and cilostazol could be discontinued three months after the HT. Oral administration of cilostazol can be a therapeutic option for patients with sinus bradycardia following HT, who need positive chronotropic support.
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Bradicardia/tratamiento farmacológico , Cilostazol/uso terapéutico , Insuficiencia Cardíaca/cirugía , Trasplante de Corazón/efectos adversos , Bradicardia/diagnóstico por imagen , Bradicardia/etiología , Gasto Cardíaco/efectos de los fármacos , Electrocardiografía/métodos , Estudios de Seguimiento , Insuficiencia Cardíaca/diagnóstico , Trasplante de Corazón/métodos , Hemodinámica/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/tratamiento farmacológico , Edema Pulmonar/diagnóstico por imagen , Edema Pulmonar/etiología , Edema Pulmonar/fisiopatología , Radiografía Torácica/métodos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Pump thrombosis (PT) is a serious complication after continuous-flow left ventricular assist device (LVAD) implantation. To detect PT, echocardiographic ramp test using left ventricular end-diastolic diameter (LVEDD) is known to be useful. However, this method has several limitations. In this study, we propose an alternative novel ramp test using the flow velocity of outflow graft (OG). A 46-year-old man underwent continuous-flow LVAD (HeartMate II, Abbott Laboratories, Lake Forest, IL, USA) implantation for advanced heart failure due to idiopathic dilated cardiomyopathy. About 2 years after implantation, he suffered from hemolysis and symptoms of heart failure, and PT was strongly suspected. The change in LVEDD was minimal with increase in pump speed (-0.06 cm/400 rotations per minute (rpm)), suggesting PT. The systolic to diastolic velocity (S/D) ratio of OG flow, which we proposed as a new indicator of PT, also showed minimal change (-0.07/400 rpm). His clinical symptoms improved with anticoagulation therapy, and the changing slope of the S/D ratio dramatically improved to -0.92/400 rpm. Although its consistency should be verified in many other cases, this novel method can be useful for detecting PT and evaluating its clinical course.
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Velocidad del Flujo Sanguíneo/fisiología , Insuficiencia Cardíaca/terapia , Corazón Auxiliar/efectos adversos , Flujo Sanguíneo Regional/fisiología , Trombosis/etiología , Función Ventricular Izquierda/fisiología , Ecocardiografía , Falla de Equipo , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Trombosis/diagnóstico , Trombosis/fisiopatologíaRESUMEN
BACKGROUND: Pacemaker implantation in patients with single ventricle is associated with poor outcomes. OBJECTIVE: The purpose of this study was to determine the reasons for the poor outcomes of pacemaker implantation. METHODS: We performed a retrospective chart review of patients with single ventricle who had undergone permanent pacemaker implantation. Patients were categorized into 3 groups based on the site of pacing and the proportion of ventricular pacing (VP) as follows: (1) atrial pacing group with atrial pacing only (n = 11); (2) low VP group with low daily VP proportion (<50%; n = 12); and (3) high VP group with high daily VP proportion (≥50%; n = 15). Pacing leads were placed at the epicardium in all patients. RESULTS: No patients in the atrial pacing or low VP groups died, whereas the survival rate in the high VP group was 58.9% and 39.3% at 10 and 20 years, respectively, after pacemaker implantation. Among the post-Fontan patients, plasma brain natriuretic peptide (BNP) levels significantly increased with the proportion of VP: 11.7, 20.3, and 28.4 pg/mL in the atrial pacing, low VP, and high VP groups, respectively (P = 0.04). In the high VP group, the plasma BNP level was significantly lower in patients with an apical pacing lead than in those with a nonapical pacing lead (27.0 pg/mL vs 82.8 pg/mL, respectively; P = .03). CONCLUSION: A higher proportion of VP was associated with poor outcome and higher plasma BNP levels, probably due to ventricular dyssynchrony. In epicardial ventricular pacing, apical pacing is better to avoid the increase in ventricular stress and plasma BNP level.
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Estimulación Cardíaca Artificial , Péptido Natriurético Encefálico/sangre , Volumen Sistólico , Corazón Univentricular , Adulto , Estimulación Cardíaca Artificial/efectos adversos , Estimulación Cardíaca Artificial/métodos , Femenino , Procedimiento de Fontan/métodos , Atrios Cardíacos/fisiopatología , Humanos , Masculino , Evaluación de Procesos y Resultados en Atención de Salud , Marcapaso Artificial/efectos adversos , Tasa de Supervivencia , Corazón Univentricular/sangre , Corazón Univentricular/mortalidad , Corazón Univentricular/fisiopatología , Corazón Univentricular/terapiaAsunto(s)
Cardiomiopatías/diagnóstico por imagen , Atrios Cardíacos/diagnóstico por imagen , Sarcoidosis/diagnóstico por imagen , Taquicardia Supraventricular/diagnóstico por imagen , Cardiomiopatías/fisiopatología , Medios de Contraste , Diagnóstico Diferencial , Ecocardiografía Transesofágica , Electrocardiografía , Femenino , Fluorodesoxiglucosa F18 , Atrios Cardíacos/fisiopatología , Humanos , Imagen por Resonancia Cinemagnética , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Radiofármacos , Sarcoidosis/fisiopatología , Taquicardia Supraventricular/fisiopatologíaRESUMEN
BACKGROUND: Trastuzumab-related cardiotoxicity (TRC) has been considered as reversible. However, recent studies have raised concern against reversibility of left ventricular (LV) systolic dysfunction in breast cancer patients treated with trastuzumab. In addition, the efficacy of medical treatment for heart failure (HF) including renin-angiotensin inhibitors and ß-blockers has not been defined in TRC. METHODS AND RESULTS: We retrospectively studied 160 patients with breast cancer receiving trastuzumab in the adjuvant (n = 129) as well as metastatic (n = 31) settings in our institution from 2006 to 2015. During the median follow-up of 3.5 years, 20 patients (15.5%) receiving adjuvant trastuzumab and 7 patients (22.6%) with metastatic breast cancer developed TRC with a mean decrease in LV ejection fraction (EF) of 19.8%. By the multivariate analysis, lower LVEF before trastuzumab (OR 1.30; 95% CI 1.16-1.48; P = 0.0001) independently predicted subsequent development of TRC. LV systolic dysfunction was reversible in 20 patients (74.1%) with a median time to recovery of 7 months, which was independently associated with lower dose of anthracyclines (OR 1.03; 95% CI 1.01-1.07, P = 0.020) and an introduction of renin-angiotensin inhibitors and ß-blockers (OR 19.0; 95% CI 1.00-592.2, P = 0.034). CONCLUSIONS: Irreversible decline in LVEF occurred in patients who underwent trastuzumab in combination with anthracyclines with a relatively high frequency. The lower cumulative dose of anthracyclines and HF treatment including renin-angiotensin inhibitors and ß-blockers were both independent predictors to enhance LV functional reversibility in patients with TRC.
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Antagonistas Adrenérgicos beta/uso terapéutico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Trastuzumab/efectos adversos , Disfunción Ventricular Izquierda/prevención & control , Función Ventricular Izquierda/efectos de los fármacos , Antineoplásicos Inmunológicos/efectos adversos , Antineoplásicos Inmunológicos/uso terapéutico , Cardiotoxicidad , Ecocardiografía , Femenino , Estudios de Seguimiento , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatología , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Volumen Sistólico/efectos de los fármacos , Trastuzumab/uso terapéutico , Resultado del Tratamiento , Disfunción Ventricular Izquierda/inducido químicamente , Disfunción Ventricular Izquierda/fisiopatología , Función Ventricular Izquierda/fisiologíaRESUMEN
Higher heart rate (HR) is independently related to worse outcomes in various cardiac diseases, including hypertension, coronary artery disease, and heart failure (HF). HR is determined by the pacemaker activity of cells within the sinoatrial node. The hyperpolarization-activated cyclic nucleotide-gated (HCN) 4 channel, one of 4 HCN isoforms, generates the If current and plays an important role in the regulation of pacemaker activity in the sinoatrial node. Ivabradine is a novel and only available HCN inhibitor, which can reduce HR and has been approved for stable angina and chronic HF in many countries other than Japan. In this review, we summarize the current knowledge of the HCN4 channel and ivabradine, including the function of HCN4 in cardiac pacemaking, the mechanism of action of If inhibition by ivabradine, and the pharmacological and clinical effects of ivabradine in cardiac diseases as HF, coronary artery disease, and atrial fibrillation.