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Aims: The Biventricular vs Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block (BLOCK-HF) demonstrated that biventricular (BiV) pacing resulted in better clinical and structural outcomes compared to right ventricular (RV) pacing in patients with atrioventricular (AV) block and reduced left ventricular ejection fraction (LVEF; ≤50%). This study investigated the cost-effectiveness of BiV vs RV pacing in the patient population enrolled in the BLOCK-HF trial. Methods: All-cause mortality, New York Heart Association (NYHA) Class distribution over time, and NYHA-specific heart failure (HF)-related healthcare utilization rates were predicted using statistical models based on BLOCK-HF patient data. A proportion-in-state model calculated cost-effectiveness from the Medicare payer perspective. Results: The predicted patient survival was 6.78 years with RV and 7.52 years with BiV pacing, a 10.9% increase over lifetime. BiV pacing resulted in 0.41 more quality-adjusted life years (QALYs) compared to RV pacing, at an additional cost of $12,537. The "base-case" incremental cost-effectiveness ratio (ICER) was $30,860/QALY gained. Within the clinical sub-groups, the highest observed ICER was $43,687 (NYHA Class I). Patients receiving combined BiV pacing and defibrillation (BiV-D) devices were projected to benefit more (0.84 years gained) than BiV pacemaker (BiV-P) recipients (0.49 years gained), compared to dual-chamber pacemakers. Conclusions: BiV pacing in AV block patients improves survival and attenuates HF progression compared to RV pacing. ICERs were consistently below the US acceptability threshold ($50,000/QALY). From a US Medicare perspective, the additional up-front cost associated with offering BiV pacing to the BLOCK-HF patient population appears justified.
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Terapia de Resincronización Cardíaca/economía , Análisis Costo-Beneficio , Insuficiencia Cardíaca/cirugía , Bloqueo Atrioventricular/cirugía , Método Doble Ciego , Femenino , Política de Salud , Ventrículos Cardíacos/fisiopatología , Ventrículos Cardíacos/cirugía , Humanos , Masculino , New York , Marcapaso Artificial , Aceptación de la Atención de Salud , Calidad de Vida , Años de Vida Ajustados por Calidad de Vida , Función VentricularRESUMEN
BACKGROUND: Chronic kidney disease (CKD) is associated with increased risk of cardiovascular disease (CVD) and it is especially common among Blacks. Left ventricular hypertrophy (LVH) is an important subclinical marker of CVD, but there are limited data on racial variation in left ventricular structure and function among persons with CKD. METHODS: In a cross-sectional analysis of the Chronic Renal Insufficiency Cohort Study, we compared the prevalence of different types of left ventricular remodeling (concentric hypertrophy, eccentric hypertrophy, and concentric remodeling) by race/ethnicity. We used multinomial logistic regression to test whether race/ethnicity associated with different types of left ventricular remodeling independently of potential confounding factors. RESULTS: We identified 1,164 non-Hispanic Black and 1,155 non-Hispanic White participants who completed Year 1 visits with echocardiograms that had sufficient data to categorize left ventricular geometry type. Compared to non-Hispanic Whites, non-Hispanic Blacks had higher mean left ventricular mass index (54.7 ± 14.6 vs. 47.4 ± 12.2 g/m2.7; P < 0.0001) and prevalence of concentric LVH (45.8% vs. 24.9%). In addition to higher systolic blood pressure and treatment with >3 antihypertensive medications, Black race/ethnicity was independently associated with higher odds of concentric LVH compared to White race/ethnicity (odds ratio: 2.73; 95% confidence interval: 2.02, 3.69). CONCLUSION: In a large, diverse cohort with CKD, we found significant differences in left ventricular mass and hypertrophic morphology between non-Hispanic Blacks and Whites. Future studies will evaluate whether higher prevalence of LVH contribute to racial/ethnic disparities in cardiovascular outcomes among CKD patients.
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Insuficiencia Renal Crónica/patología , Disfunción Ventricular Izquierda/patología , Adulto , Anciano , Población Negra , Presión Sanguínea , Estudios de Cohortes , Estudios Transversales , Electrocardiografía , Etnicidad , Femenino , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Hipertrofia Ventricular Izquierda/epidemiología , Hipertrofia Ventricular Izquierda/patología , Masculino , Persona de Mediana Edad , Prevalencia , Insuficiencia Renal Crónica/epidemiología , Factores Socioeconómicos , Disfunción Ventricular Izquierda/epidemiología , Remodelación Ventricular , Población Blanca , Adulto JovenRESUMEN
Despite therapeutic advances that improve longevity and quality of life, heart failure (HF) remains a relentless disease. At the end stage of HF, patients may become eligible for mechanical circulatory support (MCS) for the indications of stabilising acute cardiogenic shock or for chronic HF management. MCS use is growing rapidly in the USA and some countries of the European Union, especially in transplant-ineligible patients. In others, it remains largely a tool to stabilise patients until heart transplant. MCS comprises a heterogeneous group of temporary and durable devices which augment or replace the pumping function of one or both ventricles, with postimplant 2â year survival rivalling that of transplant in selected, lower-risk patients. In transplant-eligible and non-transplant-eligible patients, improvement in end-organ perfusion, functional capacity and quality of life have been noted. Even for optimal candidates, however, there are a host of potential complications that require constant vigilance of a coordinated care team. Recently, there has been official recognition of the importance of palliative care expertise in advance care planning preimplant and management of patients with ventricular assist devices at the end of their lives.
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Insuficiencia Cardíaca/terapia , Corazón Auxiliar , Función Ventricular Izquierda , Función Ventricular Derecha , Enfermedad Aguda , Enfermedad Crónica , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/fisiopatología , Trasplante de Corazón , Humanos , Selección de Paciente , Diseño de Prótesis , Recuperación de la Función , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Cardiac resynchronization therapy (CRT) reduces morbidity and mortality and improves symptoms in patients with systolic heart failure (HF) and ventricular dyssynchrony. This randomized, double-blind, controlled study evaluated whether optimizing the interventricular stimulating interval (V-V) to sequentially activate the ventricles is clinically better than simultaneous V-V stimulation during CRT. METHODS: Patients with New York Heart Association (NYHA) III or IV HF, meeting both CRT and implantable cardioverter-defibrillator indications, randomly received either simultaneous CRT or CRT with optimized V-V settings for 6 months. Patients also underwent echocardiography-guided atrioventricular delay optimization to maximize left ventricular filling. The V-V optimization involved minimizing the left ventricular septal to posterior wall motion delay during CRT. The primary objective was to demonstrate noninferiority using a clinical composite end point that included mortality, HF hospitalization, NYHA functional class, and patient global assessment. Secondary end points included changes in NYHA classification, 6-minute hall walk distance, quality of life, peak VO(2), and event-free survival. RESULTS: The composite score improved in 75 (64.7%) of 116 simultaneous patients and in 92 (75.4%) of 122 optimized patients (P < .001, for noninferiority). A prespecified test of superiority showed that more optimized patients improved (P = .03). New York Heart Association functional class improved in 58.0% of simultaneous patients versus 75.0% of optimized patients (P = .01). No significant differences in exercise capacity, quality of life, peak VO(2), or HF-related event rate between the 2 groups were observed. CONCLUSIONS: These findings demonstrate modest clinical benefit with optimized sequential V-V stimulation during CRT in patients with NYHA class III and IV HF. Optimizing V-V timing may provide an additional tool for increasing the proportion of patients who respond to CRT.
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Estimulación Cardíaca Artificial/métodos , Terapia de Resincronización Cardíaca , Adulto , Anciano , Supervivencia sin Enfermedad , Método Doble Ciego , Ecocardiografía , Femenino , Ventrículos Cardíacos , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Calidad de Vida , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , CaminataRESUMEN
The autosomal-recessive disorder Friedreich's ataxia is characterized by progressive ataxia, often in association with cardiomyopathy. The most frequent cause of death is cardiac dysfunction, reflecting congestive heart failure, ventricular arrhythmias and cardio-embolic stroke. With the discovery of the underlying genetic mutation, a variety of novel therapies are now progressing into clinical trials. Consequently, it is crucial to understand the features of cardiomyopathy in this disease and how new treatments may improve cardiac function. The present artcle reviews the molecular basis of the disease, the clinical features of cardiomyopathy in Friedreich's ataxia and the upcoming therapies.
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Cardiomiopatías/etiología , Ataxia de Friedreich/fisiopatología , Animales , Arritmias Cardíacas/etiología , Arritmias Cardíacas/terapia , Cardiomiopatías/fisiopatología , Cardiomiopatías/terapia , Ensayos Clínicos como Asunto , Progresión de la Enfermedad , Ataxia de Friedreich/genética , Ataxia de Friedreich/terapia , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/terapia , Humanos , Mutación , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/terapiaAsunto(s)
Ecocardiografía/estadística & datos numéricos , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/epidemiología , Hallazgos Incidentales , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/epidemiología , Femenino , Humanos , MasculinoRESUMEN
This study aimed to identify the anatomic and pathologic structural cardiac abnormalities in conjoined twins and to focus on those that have prevented the successful separation of conjoined hearts. A retrospective review was undertaken to examine consecutive cases of thoracopagus conjoined twins with conjoined hearts evaluated at The Children's Hospital of Philadelphia from 1 January 1980 through 6 October 2008. The records included autopsy and surgical findings as well as clinical reports. The study group included nine sets of conjoined twins with a mean gestational age at birth of 33.8 ± 5.5 weeks. Three twin pairs were stillborn. Five twin pairs died afterward. One pair died of cardiopulmonary failure. The median age at death was 22 days (range, 0-345 days). Major congenital heart disease was present in 94.4% (17/18) of the hearts, and 72.2% (13/18) of the hearts had single-ventricle physiology. Total anomalous pulmonary venous return occurred in 39% (7/18) of the cases. The clinical outcome for thoracopagus twins with conjoined hearts remains poor because of inability to separate conjoined and single ventricles. Surgical nonintervention and palliative care should be strongly considered for these patients.
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Enfermedades en Gemelos , Cardiopatías Congénitas/patología , Tórax/anomalías , Gemelos Siameses/fisiopatología , Cardiopatías Congénitas/mortalidad , Cardiopatías Congénitas/fisiopatología , Humanos , Lactante , Recién Nacido , Estudios Retrospectivos , Gemelos Siameses/patologíaRESUMEN
The noninvasive estimation of pulmonary artery systolic pressure (PASP) has become a standard component of the echocardiographic examination. Our aim was to evaluate the accuracy of this modality in a large series of unselected studies obtained in clinical practice. All right heart catheterizations during a 4-year period were reviewed. Studies with echocardiographic findings available within 48 hours were evaluated for PASP agreement. In an effort to mirror clinical practice, the right heart catheterization findings were used as the reference standard and the PASP values were taken directly from the respective clinical reports. Overall, 792 right heart catheterization-echocardiogram pairs were identified. Echocardiographic PASP could not be estimated in 174 of these studies (22.0%). The correlation between modalities was moderate, but agreement was poor (bias 9.0%, 95% limits of agreement -53.2% to 71.2%, r = 0.52, p <0.001). Misclassification of clinical PASP categories occurred more often than not (54.4%). Multivariate analysis using multiple potential sources of error could only account for 3.2% of the total variation in the discrepancy between the study modalities (p = 0.003). In conclusion, noninvasively estimated PASP had limited agreement with the invasively determined PASP, and misclassification of PASP clinical categories occurred frequently. Given the widespread use of echocardiographically determined PASP, these data are in need of replication in a large prospective study.
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Determinación de la Presión Sanguínea/métodos , Ecocardiografía/métodos , Presión Esfenoidal Pulmonar/fisiología , Determinación de la Presión Sanguínea/normas , Cateterismo Cardíaco , Interpretación Estadística de Datos , Humanos , Estudios Prospectivos , Curva ROC , Reproducibilidad de los Resultados , SístoleRESUMEN
BACKGROUND: The aim of this study was to investigate the ability of transthoracic echocardiography (TTE) to detect vegetations and the relationship between blood cultures and transesophageal echocardiography (TEE). METHODS: Five hundred eleven TTE and TEE pairs performed to evaluate endocarditis were retrospectively analyzed. Vegetation on TTE, prosthetic valve, change in regurgitation, and blood cultures were correlated with vegetation on TEE. RESULTS: TTE detected 45% of vegetations seen on TEE. There was no difference for prosthetic valves. Prosthetic valves (odds ratio, 1.7; P = .03) and increased regurgitation (odds ratio, 1.7; P = .01) were associated with vegetations on TEE; staphylococcal bacteremia and fungemia were not. Negative blood cultures were associated with negative results on TEE (P < .0001), but 27% of patients with prosthetic valves had culture-negative endocarditis or nonbacterial thrombotic endocarditis, and 6% had abscesses missed by TTE. CONCLUSION: This study demonstrates a limited capacity of TTE to detect vegetations. TEE may be an appropriate initial study to evaluate prosthetic valves. TEE for culture-negative endocarditis deserves further study.
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Ecocardiografía Transesofágica , Ecocardiografía , Endocarditis/diagnóstico por imagen , Endocarditis/microbiología , Sangre/microbiología , Prótesis Valvulares Cardíacas/microbiología , Humanos , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
Recent reports have demonstrated the adverse effects of venous congestion on renal function (RF) and challenged the assumption that worsening RF is driven by decreased cardiac output (CO). We hypothesized that diuresis in patients with right ventricular (RV) dysfunction, despite decreased CO, would lead to a decrease in venous congestion and resultant improvement in RF. We reviewed consecutive admissions with a discharge diagnosis of heart failure. RV function was assessed by multiple echocardiographic methods and those with >or=2 measurements of RV dysfunction were considered to have significant RV dysfunction. Worsening RF was defined as an increase in creatinine of >or=0.3 mg/dl and improved RF as improvement in glomerular filtration rate >or=25%. A total of 141 admissions met eligibility criteria; 34% developed worsening RF. Venous congestion was more common in those with RV dysfunction (odds ratio [OR] 3.3, p = 0.009). All measurements of RV dysfunction excluding RV dilation correlated with CO (p <0.05). Significant RV dysfunction predicted a lower incidence of worsening RF (OR 0.21, p <0.001) and a higher incidence of improved RF (OR 6.4, p <0.001). CO emerged as a significant predictor of change in glomerular filtration rate during hospitalization in those without significant RV dysfunction (r = 0.38, p <0.001). In conclusion, RV dysfunction is a strong predictor of improved renal outcomes in patients with acute decompensated heart failure, an effect likely mediated by relief of venous congestion.
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Insuficiencia Cardíaca/fisiopatología , Hiperemia/fisiopatología , Enfermedades Renales/fisiopatología , Disfunción Ventricular Derecha/fisiopatología , Anciano , Biomarcadores/sangre , Gasto Cardíaco Bajo/fisiopatología , Estudios de Cohortes , Creatinina/sangre , Diuréticos/uso terapéutico , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/terapia , Hospitales Universitarios , Humanos , Hiperemia/sangre , Hiperemia/diagnóstico por imagen , Hiperemia/terapia , Incidencia , Enfermedades Renales/complicaciones , Enfermedades Renales/diagnóstico por imagen , Enfermedades Renales/terapia , Pruebas de Función Renal , Tiempo de Internación , Masculino , Persona de Mediana Edad , Péptido Natriurético Encefálico/sangre , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Ultrasonografía , Disfunción Ventricular Derecha/sangre , Disfunción Ventricular Derecha/diagnóstico por imagen , Disfunción Ventricular Derecha/terapiaRESUMEN
Although resting hemodynamic load has been extensively investigated as a determinant of left ventricular (LV) hypertrophy, little is known about the relationship between provoked hemodynamic load and the risk of LV hypertrophy. We studied central pressure-flow relations among 40 hypertensive and 19 normotensive adults using carotid applanation tonometry and Doppler echocardiography at rest and during a 40% maximal voluntary forearm contraction (handgrip) maneuver. Carotid-femoral pulse wave velocity (CF-PWV) was measured at rest. Hypertensive subjects demonstrated various abnormalities in resting and induced pulsatile load. Isometric exercise significantly increased systemic vascular resistance, aortic characteristic impedance (Zc), induced earlier wave reflections, increased augmentation index, and decreased total arterial compliance (TAC; all P < or = 0.01). In hypertensive subjects, CF-PWV was the strongest resting predictor of LV mass index (LVMI) and remained an independent predictor after adjustment for age, gender, systemic vascular resistance, reflection magnitude, aortic Zc, and TAC (beta = 2.52 m/s; P < 0.0001). Age, sex, CF-PWV, and resting hemodynamic indexes explained 48% of the interindividual variability in LVMI. In stepwise regression, TAC (beta = -17.85; P < 0.0001) during handgrip, Zc during handgrip (beta = -150; P < 0.0001), and the change in the timing of wave reflections during handgrip (beta = -0.63; P = 0.03) were independent predictors of LVMI. A model that included indexes of provoked hemodynamic load explained 68% of the interindividual variability in LVMI. Hemodynamic load provoked by isometric exercise strongly predicts LVMI in hypertension. The magnitude of this association is far greater than for resting hemodynamic load, suggesting that provoked testing captures important arterial properties that are not apparent at rest and is advantageous to assess dynamic arterial load in hypertension.
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Presión Sanguínea/fisiología , Arterias Carótidas/fisiopatología , Ejercicio Físico/fisiología , Hipertensión/complicaciones , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Flujo Sanguíneo Regional/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Gasto Cardíaco/fisiología , Estudios de Casos y Controles , Ecocardiografía Tridimensional , Fatiga/fisiopatología , Femenino , Fuerza de la Mano/fisiología , Frecuencia Cardíaca/fisiología , Ventrículos Cardíacos/patología , Ventrículos Cardíacos/fisiopatología , Humanos , Hipertensión/fisiopatología , Hipertrofia Ventricular Izquierda/patología , Hipertrofia Ventricular Izquierda/fisiopatología , Masculino , Manometría , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Volumen Sistólico/fisiologíaRESUMEN
BACKGROUND: Targeted delivery of mesenchymal precursor cells (MPCs) can modify left ventricular (LV) cellular and extracellular remodeling after myocardial infarction (MI). However, whether and to what degree LV remodeling may be affected by MPC injection post-MI, and whether these effects are concentration-dependent, remain unknown. METHODS AND RESULTS: Allogeneic MPCs were expanded from sheep bone marrow, and direct intramyocardial injection was performed within the borderzone region 1 hour after MI induction (coronary ligation) in sheep at the following concentrations: 25x10(6) (25 M, n=7), 75x10(6) (75 M, n=7), 225x10(6) (225 M, n=10), 450x10(6) (450 M, n=8), and MPC free media only (MI Only, n=14). LV end diastolic volume increased in all groups but was attenuated in the 25 and 75 M groups. Collagen content within the borderzone region was increased in the MI Only, 225, and 450 M groups, whereas plasma ICTP, an index of collagen degradation, was highest in the 25 M group. Within the borderzone region matrix metalloproteinases (MMPs) and MMP tissue inhibitors (TIMPs) also changed in a MPC concentration-dependent manner. For example, borderzone levels of MMP-9 were highest in the 25 M group when compared to the MI Only and other MPC treatment group values. CONCLUSIONS: MPC injection altered collagen dynamics, MMP, and TIMP levels in a concentration-dependent manner, and thereby influenced indices of post-MI LV remodeling. However, the greatest effects with respect to post-MI remodeling were identified at lower MPC concentrations, thus suggesting a therapeutic threshold exists for this particular cell therapy.
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Trasplante de Células Madre Mesenquimatosas , Infarto del Miocardio/terapia , Remodelación Ventricular , Animales , Colágeno/metabolismo , Femenino , Metaloproteinasas de la Matriz/análisis , Infarto del Miocardio/patología , Infarto del Miocardio/fisiopatología , Ovinos , Inhibidor Tisular de Metaloproteinasa-1/análisis , Función Ventricular IzquierdaRESUMEN
Echocardiography serves an extremely important role in the diagnosis and management of patients with heart failure. The various stages of structural and functional changes that constitute progressive left ventricle remodeling have all been characterized by two-dimensional echocardiography. In addition, echocardiography has defined the transition from compensated hypertrophy to left ventricle dilatation and progression to end-stage heart failure. Echocardiography has also played an important role in clinical heart failure trials of beta-adrenergic blocking agents and angiotensin-converting enzyme inhibitors and angiotensin receptor blockers and demonstrated their efficacy in heart failure.
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Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/fisiopatología , Ventrículos Cardíacos/diagnóstico por imagen , Función Ventricular Izquierda , Dilatación Patológica , Ecocardiografía Doppler en Color , Ecocardiografía Tridimensional , Insuficiencia Cardíaca/complicaciones , Ventrículos Cardíacos/patología , Ventrículos Cardíacos/fisiopatología , Humanos , Insuficiencia de la Válvula Mitral/diagnóstico por imagen , Insuficiencia de la Válvula Mitral/etiología , Contracción Miocárdica , Volumen Sistólico , Sístole , Disfunción Ventricular Izquierda/diagnóstico por imagen , Remodelación VentricularRESUMEN
OBJECTIVE: Elective ascending aortic replacement is recommended to prevent acute type A aortic dissection when any segment of the proximal aorta is greater than 5.5 cm. However, little data exist that meticulously describe the size of the ascending aorta at multiple levels in patients who suffer acute type A dissections. We sought to definitively characterize the size distribution of the proximal aorta in this patient population. METHODS: Preoperative transesophageal echocardiography was used to measure the diameter of the proximal aorta at the aortic annulus, in the sinus segment, at the sinotubular junction and in the ascending aorta in 177 non-Marfan patients with tricuspid aortic valves who presented to one institution over a 10-year period with an acute type A dissection. Predicted aortic diameters for each patient based on the individual's age, gender and body size were also calculated at all four aortic positions using previously published regression equations derived from a large cohort of normal patients. RESULTS: Sixty patients were female (33.9%; aged 67+/-12 years) and 117 were male (66.1%; aged 60+/-17 years). Sixty-two percent of all patients had maximum aortic diameters less than 5.5 cm at time of dissection and 42% of patients had maximum aortic diameters less than 5.0 cm. Over 20% of all patients had maximal aortic dimensions of less than 4.5 cm. In women, 12% of the dissected aortas had a maximal dimension less than 4.0 cm. CONCLUSIONS: The majority of patients with acute type A aortic dissection present with aortic diameters <5.5 cm and thus do not fall within current guidelines for elective ascending aortic replacement. Methods other than size measurement of the ascending aorta are needed to identify patients at risk for dissection. Aggressive medical management of patients with ascending aortic diameters over 4 cm is warranted. Preventative replacement of the ascending aorta at 4.5 cm should be considered especially at high volume aortic surgery centers and patients having cardiac surgery for other indications.
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Aorta/cirugía , Aneurisma de la Aorta/cirugía , Disección Aórtica/prevención & control , Enfermedad Aguda , Anciano , Disección Aórtica/diagnóstico por imagen , Disección Aórtica/patología , Aorta/diagnóstico por imagen , Aorta/patología , Aneurisma de la Aorta/diagnóstico por imagen , Aneurisma de la Aorta/patología , Implantación de Prótesis Vascular , Ecocardiografía Transesofágica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Selección de Paciente , Estudios Retrospectivos , Factores de Riesgo , Factores SexualesRESUMEN
BACKGROUND: This experiment assessed the dose-dependent effect of a unique allogeneic STRO-3-positive mesenchymal precursor cell (MPC) on postinfarction left ventricular (LV) remodeling. The MPCs were administered in a manner that would simulate an off-the-self, early postinfarction, preventative approach to cardiac cell therapy in a sheep transmural myocardial infarct (MI) model. METHODS: Allogeneic MPCs were isolated from male crossbred sheep. Forty-six female sheep underwent coronary ligation to produce a transmural LV anteroapical infarction. One hour after infarction, the borderzone myocardium received an injection of 25, 75, 225, or 450 x 10(6) MPCs, or cell medium. Echocardiography was performed at 4 and 8 weeks after MI to quantify LV end-diastolic (LVEDV) and end-systolic volumes (LVESV), ejection fraction (EF), and infarct expansion. CD31 and smooth muscle actin (SMA) immunohistochemical staining was performed on infarct and borderzone specimens to quantify vascular density. RESULTS: Compared with controls, low-dose (25 and 75 x 10(6) cells) MPC treatment significantly attenuated infarct expansion and increases in LVEDV and LVESV. EF was improved at all cell doses. CD31 and SMA immunohistochemical staining demonstrated increased vascular density in the borderzone only at the lower cell doses. There was no evidence of myocardial regeneration within the infarct. CONCLUSION: Allogeneic STRO-3 positive MPCs attenuate the remodeling response to transmural MI in a clinically relevant large-animal model. This effect is associated with vasculogenesis and arteriogenesis within the borderzone and infarct and is most pronounced at lower cell doses.
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Trasplante de Células Madre Mesenquimatosas , Infarto del Miocardio/complicaciones , Remodelación Ventricular , Animales , Recuento de Células , Femenino , Trasplante de Células Madre Mesenquimatosas/métodos , Trasplante de Células Madre Mesenquimatosas/estadística & datos numéricos , Infarto del Miocardio/patología , OvinosRESUMEN
BACKGROUND: Early infarct expansion after coronary occlusion compromises contractile function in perfused myocardial regions and promotes adverse long-term left ventricular (LV) remodeling. We hypothesized that injection of a tissue-expanding dermal filler material into a myocardial infarction (MI) would attenuate infarct expansion and limit LV remodeling. METHODS: Fifteen sheep were subjected to an anteroapical MI involving approximately 20% of the LV followed by the injection of 1.3 mL of a calcium hydroxyapatite-based dermal filler into the infarct. Real-time three-dimensional echocardiography was performed at baseline, 30 minutes after MI, and 15 minutes after injection to assess infarct expansion. Sixteen additional sheep were subjected to the same infarction and followed echocardiographically and hemodynamically for 4 weeks after MI to assess chronic remodeling. Eight animals had injection with dermal filler as described above immediately after MI, and 8 animals were injected with an equal amount of saline solution. RESULTS: All animals exhibited infarct expansion soon after coronary occlusion. The regional ejection fraction of the apex became negative after infarction, consistent with systolic dyskinesia. Injection of the dermal filler converted the apical wall motion from dyskinetic to akinetic and resulted immediately in significant decreases in global, regional, and segmental LV volumes. Chronically, relative to saline control, dermal filler injection significantly reduced LV end-systolic volume (62.2 +/- 3.6 mL versus 44.5 +/- 3.9 mL; p < 0.05) and improved global ejection fraction (0.295 +/- 0.016 versus 0.373 +/- 0.017; p < 0.05) at 4 weeks after infarction. CONCLUSIONS: Injection of an acellular dermal filler into an MI immediately after coronary occlusion reduces early infarct expansion and limits chronic LV remodeling.
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Durapatita/farmacología , Infarto del Miocardio/tratamiento farmacológico , Remodelación Ventricular/efectos de los fármacos , Animales , Biopsia con Aguja , Fármacos Dermatológicos/farmacología , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Ecocardiografía Transesofágica , Geles/farmacología , Inmunohistoquímica , Inyecciones Intralesiones , Masculino , Microesferas , Contracción Miocárdica/efectos de los fármacos , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/patología , Probabilidad , Distribución Aleatoria , Valores de Referencia , Sensibilidad y Especificidad , Remodelación Ventricular/fisiologíaRESUMEN
BACKGROUND: Mild hypothermia (< 4 degrees C) improves myocardial salvage after infarct reperfusion in animals and in early clinical studies. In this experiment the effect of mild hypothermia during ischemia and early reperfusion on long-term postinfarction left ventricular (LV) remodeling was assessed in an ovine infarct model. METHODS: In the initial phase of the experiment the effect of progressive degrees of hypothermia on infarct size was quantified. Thirty-eight male sheep were subjected to 1 hour of ischemia using a standardized anteroapical infarct followed by 3 hours of reperfusion. Temperature was maintained at either 39.5 degrees C (n = 11), 38.5 degrees C (n = 7), 37.5 degrees C (n = 7), 36.5 degrees C (n = 7), or 35.5 degrees C (n = 6) for the entire period of ischemia and reperfusion. The area at risk (AR) and infarct size as a percentage of AR (I/AR) were determined with a double staining and planimetry technique. In the second phase of the study, chronic post-infarction remodeling was assessed in animals with nonreperfused infarcts (n = 6), 1 hour of ischemia followed by reperfusion at 39.5 degrees C (n = 6) and 1 hour of ischemia followed by reperfusion at 37.5 degrees C (n = 6). Remodeling was determined at 8 weeks after infarction using echocardiography. RESULTS: The I/AR in the 39.5 degrees C, 38.5 degrees C, 37.5 degrees C, 36.5 degrees C, and the 35.5 degrees C groups was 71.8 +/- 3.0%, 63.1 +/- 1.9%, 49.4 +/- 1.4%, 38.7 +/- 1.4%, and 21.7 +/- 2.2%, respectively (p < 0.05 between all groups). In the chronic study LV end systolic volume at 8 weeks after infarction was 81 +/- 8 mL in the nonreperfused group, 57 +/- 4 mL in the 39.5 degrees C reperfusion group, and 41 +/- 3 mL in the 37.5 degrees C reperfusion group (p < 0.05 for between group differences). CONCLUSIONS: Subtle degrees of hypothermia can significantly improve immediate myocardial salvage and long-term LV remodeling after infarct reperfusion.
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Hipotermia Inducida/métodos , Precondicionamiento Isquémico Miocárdico/métodos , Infarto del Miocardio/patología , Infarto del Miocardio/terapia , Daño por Reperfusión Miocárdica/prevención & control , Remodelación Ventricular/fisiología , Análisis de Varianza , Animales , Circulación Coronaria/fisiología , Modelos Animales de Enfermedad , Hemodinámica/fisiología , Inmunohistoquímica , Masculino , Contracción Miocárdica/fisiología , Reperfusión Miocárdica/métodos , Daño por Reperfusión Miocárdica/patología , Probabilidad , Distribución Aleatoria , Valores de Referencia , Sensibilidad y Especificidad , TemperaturaRESUMEN
Patients with heart failure show a wide variety of alterations in left ventricular (LV) volume, mass, and function. The purpose of this study was to define the common patterns of LV structural and functional remodeling and consider their clinical implications in patients with chronic heart failure. Two-dimensional echocardiograms obtained during the screening phase of a study involving patients (n = 315) with chronic heart failure were used to calculate LV volume, mass, geometry, and ejection fraction (EF). Inclusion required the diagnosis of heart failure in symptomatic patients on medical therapy. Measures of LV size or function were not used as inclusion or exclusion criteria. Plots of EF against LV end-diastolic volume (EDV) showing an inverse curvilinear relation allowed a description of 4 remodeling patterns. Pattern A (n = 66) was defined as normal EDV (<91 ml/m(2)) and normal EF (> or =50%); 65% of these patients showed LV hypertrophy or concentric remodeling. Pattern B (n = 65) was defined as normal EDV and depressed EF; hypertrophy or concentric remodeling was present in 63%. Pattern C (n = 175) was defined as increased EDV and depressed EF; eccentric hypertrophy was present in 94%. Pattern D (n = 9) was defined as increased EDV and normal EF; eccentric hypertrophy was present in 88%. In conclusion, these patterns of remodeling encompass a wide spectrum of geometric changes with different clinical and pathophysiologic features and possibly different management strategies.
Asunto(s)
Insuficiencia Cardíaca/patología , Insuficiencia Cardíaca/fisiopatología , Hipertrofia Ventricular Izquierda/patología , Hipertrofia Ventricular Izquierda/fisiopatología , Diástole , Ecocardiografía , Insuficiencia Cardíaca/diagnóstico por imagen , Humanos , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Factores de Riesgo , Volumen Sistólico , SístoleRESUMEN
Remodeling reflects the structural and functional deterioration that occurs in heart failure. Indices of remodeling constitute an important marker of the severity of heart failure, and reverse remodeling is an accepted goal in the treatment of heart failure. Cardiac resynchronization therapy (CRT) has been shown to reverse the remodeling process by improving ventricular size, shape, and mass and reducing mitral regurgitation in the short and long term. Diastolic function, right ventricular size, and atria exhibit reverse remodeling. Trials of medical therapy for heart failure strongly link remodeling indices with outcomes, and emerging data suggest that remodeling indices may be among the most accurate predictors of long-term morbidity and mortality in heart failure patients with CRT devices. This review discusses remodeling and focuses on the evidence for CRT-induced reverse remodeling.