RESUMEN
Anemia is associated with a poor prognosis in heart failure with preserved ejection fraction (HFpEF), but the reasons underlying this association are unclear. Previous studies have reported an association between anemia and diastolic dysfunction. However, these studies used volume- and flow-dependent indexes of diastolic dysfunction. We hypothesized that in HFpEF, anemia is more closely associated with volume status and not markers of intrinsic myocardial dysfunction. We prospectively studied 419 outpatients in a systematic HFpEF program, all of whom underwent hemoglobin measurement and comprehensive echocardiography. Longitudinal, radial, and circumferential strain were also measured in 311 patients. We defined anemia as hemoglobin <12g/dL in women and <13g/dL in men. Linear and Cox regression analyses were used to determine the association between anemia and echocardiographic/strain variables and adverse outcomes, respectively. Over half (224/419 [53%]) of the HFpEF patients had anemia. Anemia was associated with volume (preload)-dependent markers of diastolic dysfunction including echocardiographic E/A (pâ¯=â¯0.004) and E/e' ratio (pâ¯=â¯0.014) and elevated right heart pressures such as right atrial pressure (pâ¯=â¯0.002) and pulmonary artery systolic pressure (p<0.001). Anemia was not associated with markers of intrinsic myocardial dysfunction such as lateral e' (pâ¯=â¯0.16) and septal e' (pâ¯=â¯0.65) velocities or echocardiographic strain parameters (p > 0.05 for all comparisons). Anemia was associated with the combined outcome of cardiovascular hospitalization or death (hazard ratioâ¯=â¯1.50 [95% confidence interval 1.20, 1.88]; p < 0.001). In conclusion, anemia in HFpEF is associated with markers of volume status and not intrinsic markers of myocardial dysfunction.
Asunto(s)
Anemia/fisiopatología , Insuficiencia Cardíaca/fisiopatología , Disfunción Ventricular Izquierda/fisiopatología , Anciano , Biomarcadores/análisis , Diástole/fisiología , Ecocardiografía , Hemoglobinas/análisis , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Volumen Sistólico/fisiologíaRESUMEN
BACKGROUND: The ratio of the diameter of the pulmonary artery (PA) to the diameter of the aorta (PA:A) on computed tomography (CT) imaging is associated with both COPD exacerbation and pulmonary hypertension. The mechanisms of PA enlargement in COPD are poorly understood. METHODS: In this retrospective, single center study we evaluated pulmonary function, CT scans, right heart catheterizations, and echocardiography in 88 subjects with mild-to-moderately severe COPD. A sensitivity analysis was performed in 43 subjects in whom CT scan and echocardiogram were performed within 50 days of each other. To evaluate the association between PA:A ratio and echocardiographic parameters and hemodynamics, we performed simple correlations and multivariable linear regression analysis adjusting for lung function, age, sex, race, and diastolic function. RESULTS: All subjects had preserved left ventricular (LV) systolic function (LV ejection fraction 62.7%±5.5%). Among them, 56.8% had evidence of diastolic dysfunction. There was no association between PA:A ratio and the presence of diastolic dysfunction. In a multivariable model, PA:A ratio was associated with right ventricular (RV) chamber size (ß=0.015; P<0.003), RV wall thickness (ß=0.56; P<0.002), and RV function (-0.49; P=0.05). In the subgroup of subjects with testing within 50 days, the association with RV chamber size persisted (ß=0.017; P=0.04), as did the lack of association with diastolic function. PA:A ratio was also associated with elevated PA systolic pressures (r=0.62; P=0.006) and pulmonary vascular resistance (r=0.46; P=0.05), but not pulmonary arterial wedge pressure (r=0.17; P=0.5) in a subset of patients undergoing right heart catheterization. CONCLUSION: In patients with mild-to-moderately severe COPD and preserved LV function, increased PA:A ratio occurs independent of LV diastolic dysfunction. Furthermore, the PA:A ratio is associated with right heart structure and function changes, as well as pulmonary hemodynamics. These findings indicate that PA:A ratio is a marker of intrinsic pulmonary vascular changes rather than impaired LV filling.
Asunto(s)
Aorta/diagnóstico por imagen , Cateterismo Cardíaco , Angiografía por Tomografía Computarizada , Ecocardiografía , Corazón/diagnóstico por imagen , Arteria Pulmonar/diagnóstico por imagen , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Aorta/fisiopatología , Chicago , Femenino , Volumen Espiratorio Forzado , Corazón/fisiopatología , Hemodinámica , Humanos , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Hipertrofia Ventricular Izquierda/fisiopatología , Hipertrofia Ventricular Derecha/diagnóstico por imagen , Hipertrofia Ventricular Derecha/fisiopatología , Modelos Lineales , Pulmón/fisiopatología , Masculino , Análisis Multivariante , Valor Predictivo de las Pruebas , Arteria Pulmonar/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/fisiopatología , Disfunción Ventricular Derecha/diagnóstico por imagen , Disfunción Ventricular Derecha/fisiopatología , Función Ventricular Izquierda , Función Ventricular Derecha , Capacidad VitalRESUMEN
Patients with end-stage renal disease (ESRD) suffer high rates of heart failure and cardiovascular mortality, and we lack a thorough understanding of what, if any, modifiable factors contribute to cardiac dysfunction in these high-risk patients. To evaluate endothelial function as a potentially modifiable cause of cardiac dysfunction in ESRD, we investigated cross-sectional associations of macro- and microvascular dysfunction with left and right ventricular dysfunction in a well-controlled ESRD cohort. We performed comprehensive echocardiography, including tissue Doppler imaging and speckle-tracking echocardiography of the left and right ventricle, in 149 ESRD patients enrolled in an ongoing prospective, observational study. Of these participants, 123 also underwent endothelium-dependent flow-mediated dilation of the brachial artery (macrovascular function). Microvascular function was measured as the velocity time integral of hyperemic blood flow after cuff deflation. Impaired flow-mediated dilation was associated with higher left ventricular mass, independently of age and blood pressure: per 2-fold lower flow-mediated dilation, left ventricular mass was 4.1% higher (95% confidence interval, 0.49-7.7; P=0.03). After adjustment for demographics, blood pressure, comorbidities, and medications, a 2-fold lower velocity time integral was associated with 9.5% higher E/e' ratio (95% confidence interval, 1.0-16; P=0.03) and 6.7% lower absolute right ventricular longitudinal strain (95% confidence interval, 2.0-12; P=0.003). Endothelial dysfunction is a major correlate of cardiac dysfunction in ESRD, particularly diastolic and right ventricular dysfunction, in patients whose volume status is well controlled. Future investigations are needed to determine whether therapies targeting the vascular endothelium could improve cardiac outcomes in ESRD.
Asunto(s)
Arteria Braquial/fisiopatología , Endotelio Vascular/fisiopatología , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Disfunción Ventricular Izquierda/etiología , Disfunción Ventricular Izquierda/fisiopatología , Centros Médicos Académicos , Adulto , Anciano , Análisis de Varianza , Determinación de la Presión Sanguínea , California , Permeabilidad Capilar/fisiología , Estudios de Cohortes , Estudios Transversales , Progresión de la Enfermedad , Ecocardiografía Doppler/métodos , Femenino , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/fisiopatología , Humanos , Fallo Renal Crónico/diagnóstico , Modelos Lineales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Diálisis Peritoneal/métodos , Estudios Prospectivos , Diálisis Renal/métodos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Disfunción Ventricular Izquierda/diagnóstico por imagenRESUMEN
BACKGROUND: Left atrial (LA) enlargement is associated with adverse events in heart failure with preserved ejection fraction (HFpEF). However, the role of LA mechanics (ie, LA strain measures) in HFpEF has not been well studied. We hypothesized that in HFpEF, reduced (worse) LA strain is a key pathophysiologic abnormality and is a stronger correlate of adverse events than left ventricular or right ventricular longitudinal strain. METHODS AND RESULTS: We evaluated baseline LA function in 308 patients with HFpEF who were followed up longitudinally for adverse outcomes. All patients underwent speckle-tracking echocardiography for measurement of left ventricular longitudinal strain, right ventricular free wall strain, and LA booster, conduit, and reservoir strains. The clinical and prognostic significance of left ventricular, right ventricular, and LA strain measures was assessed by regression analyses. The mean age was 65±13 years, 64% were women, 26% had atrial fibrillation, and LA enlargement was present in the majority of patients (67%). Decreased LA reservoir strain was associated with increased pulmonary vascular resistance (P<0.0001) and decreased peak oxygen consumption (P=0.0001). Of the left ventricular, right ventricular, and LA strain measures, LA reservoir strain was the strongest correlate of adverse events and was independently associated with the composite outcome of cardiovascular hospitalization or death (adjusted hazard ratio per 1-SD decrease in LA strain, 1.54; 95% CI, 1.15-2.07; P=0.006). CONCLUSIONS: Abnormal indices of LA mechanics (particularly LA reservoir strain) are powerful clinical and prognostic factors in HFpEF. Unloading the LA and augmentation of LA function may be important future therapeutic targets in HFpEF. REGISTRATION INFORMATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01030991.
Asunto(s)
Función del Atrio Izquierdo , Insuficiencia Cardíaca/fisiopatología , Volumen Sistólico , Función Ventricular Izquierda , Función Ventricular Derecha , Anciano , Fenómenos Biomecánicos , Ecocardiografía Doppler , Ecocardiografía de Estrés/métodos , Prueba de Esfuerzo , Femenino , Insuficiencia Cardíaca/diagnóstico por imagen , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Consumo de Oxígeno , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Estrés MecánicoRESUMEN
BACKGROUND: Several large epidemiologic studies and clinical trials have included echocardiography, but images were stored in analog format and these studies predated tissue Doppler imaging (TDI) and speckle tracking echocardiography (STE). We hypothesized that digitization of analog echocardiograms, with subsequent quantification of cardiac mechanics using STE, is feasible, reproducible, accurate, and produces clinically valid results. METHODS: In the NHLBI HyperGEN study (N = 2234), archived analog echocardiograms were digitized and subsequently analyzed using STE to obtain tissue velocities/strain. Echocardiograms were assigned quality scores and inter-/intra-observer agreement was calculated. Accuracy was evaluated in: (1) a separate second study (N = 50) comparing prospective digital strain versus post hoc analog-to-digital strain, and (2) in a third study (N = 95) comparing prospectively obtained TDI e' velocities with post hoc STE e' velocities. Finally, we replicated previously known associations between tissue velocities/strain, conventional echocardiographic measurements, and clinical data. RESULTS: Of the 2234 HyperGEN echocardiograms, 2150 (96.2%) underwent successful digitization and STE analysis. Inter/intra-observer agreement was high for all STE parameters, especially longitudinal strain (LS). In accuracy studies, LS performed best when comparing post hoc STE to prospective digital STE for strain analysis. STE-derived e' velocities correlated with, but systematically underestimated, TDI e' velocity. Several known associations between clinical variables and cardiac mechanics were replicated in HyperGEN. We also found a novel independent inverse association between fasting glucose and LS (adjusted ß = -2.4 [95% CI -3.6, -1.2]% per 1-SD increase in fasting glucose; P < 0.001). CONCLUSIONS: Archeological echocardiography, the digitization and speckle tracking analysis of archival echocardiograms, is feasible and generates indices of cardiac mechanics similar to contemporary studies.
Asunto(s)
Conversión Analogo-Digital , Ecocardiografía/métodos , Diagnóstico por Imagen de Elasticidad/métodos , Sistemas de Información Radiológica/organización & administración , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/fisiopatología , Minería de Datos/métodos , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Procesamiento de Señales Asistido por ComputadorRESUMEN
AIMS: Chronic kidney disease (CKD) is associated with worse outcomes in heart failure with preserved ejection fraction (HFpEF). Whether this association is due the effect of CKD on intrinsic abnormalities in cardiac function is unknown. We hypothesized that CKD is independently associated with worse cardiac mechanics in HFpEF. METHODS AND RESULTS: We prospectively studied 299 patients enrolled in the Northwestern University HFpEF Program. Using the creatinine-based CKD-Epi equation to calculate estimated glomerular filtration rate (eGFR), study participants were analysed by CKD status (using eGFR <60 mL/min/1.73 m(2) to denote CKD). Indices of cardiac mechanics (longitudinal strain parameters) were measured using speckle-tracking echocardiography. Using multivariable-adjusted linear and Cox regression analyses, we determined the association between CKD and echocardiographic parameters and clinical outcomes (cardiovascular hospitalization or death). Of 299 study participants, 48% had CKD. CKD (dichotomous variable) and reduced eGFR (continuous variable) were both associated with worse cardiac mechanics indices including left atrial (LA) reservoir strain, LV longitudinal strain, and right ventricular free wall strain even after adjusting for potential confounders, including co-morbidities, EF, and volume status. For example, for each 1-SD decrease in eGFR, LA reservoir strain was 3.52% units lower (P < 0.0001) after multivariable adjustment. Reduced eGFR was also associated with worse outcomes [adjusted hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.01-1.61 per 1-SD decrease in eGFR; P = 0.039]. The association was attenuated after adjustment for indices of cardiac mechanics (P = 0.064). CONCLUSION: In HFpEF, CKD is independently associated with worse cardiac mechanics, which may explain why HFpEF patients with CKD have worse outcomes. TRIAL REGISTRATION: NCT01030991.
Asunto(s)
Insuficiencia Cardíaca , Ventrículos Cardíacos , Insuficiencia Renal Crónica , Volumen Sistólico , Anciano , Anciano de 80 o más Años , Comorbilidad , Ecocardiografía/métodos , Femenino , Tasa de Filtración Glomerular , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/fisiopatología , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatología , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/fisiopatología , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Diastolic wall strain (DWS), defined using posterior wall thickness (PWT) measurements from standard echocardiographic images (DWS = [PWT(systole)-PWT(diastole)]/PWT(systole)), has been proposed as a marker of left ventricular (LV) diastolic stiffness. However, the equation for DWS is closely related to systolic radial strain, and whether DWS is associated with abnormal cardiac mechanics (reduced systolic strains and diastolic tissue velocities) is unknown. We sought to determine the relationship between DWS and systolic and diastolic cardiac mechanics. METHODS: We calculated DWS and performed speckle-tracking analysis in a large population- and family-based study (Hypertension Genetic Epidemiology Network [HyperGEN]; N=1907 after excluding patients with ejection fraction [EF] <50% or posterior wall motion abnormalities). We measured global longitudinal, circumferential, and radial strain (GLS, GCS, and GRS, respectively) and early diastolic (e') tissue velocities, and we determined the independent association of DWS with cardiac mechanics using linear mixed effects models to account for relatedness among study participants. We also prospectively performed receiver-operating characteristic (ROC) analysis of DWS for the detection of abnormal cardiac mechanics in a separate, prospective validation study (N=35). RESULTS: In HyperGEN (age 51 ± 14 years, 59% female, 45% African-American, 57% hypertensive), mean DWS was 0.38 ± 0.05. DWS decreased with increasing comorbidity burden (ß-coefficient -0.013 [95% CI -0.015, -0.011]; P<0.0001). DWS was independently associated with GLS, GCS, GRS, and e' velocity (adjusted P<0.05) but not LV chamber compliance (EDV20, P=0.97). On prospective speckle-tracking analysis, DWS correlated well with GLS, GCS, and GRS (R=0.61, 0.57, and 0.73, respectively; P<0.001 for all comparisons). C-statistics for DWS as a diagnostic test for abnormal GLS, GCS, and GRS were: 0.78, 0.79, and 0.84, respectively. CONCLUSIONS: DWS, a simple parameter than can be calculated from routine 2D echocardiography, is closely associated with systolic strain parameters and early diastolic (e') tissue velocities but not LV chamber compliance.
Asunto(s)
Módulo de Elasticidad , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatología , Hipertensión/diagnóstico por imagen , Hipertensión/fisiopatología , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/fisiopatología , Biomarcadores , Diástole , Ecocardiografía/estadística & datos numéricos , Diagnóstico por Imagen de Elasticidad/estadística & datos numéricos , Femenino , Humanos , Hipertensión/epidemiología , Interpretación de Imagen Asistida por Computador/métodos , Masculino , Persona de Mediana Edad , Prevalencia , Reproducibilidad de los Resultados , Factores de Riesgo , Sensibilidad y Especificidad , Estrés Mecánico , Estados Unidos/epidemiología , Disfunción Ventricular Izquierda/epidemiologíaRESUMEN
OBJECTIVES: The purpose of this study was to determine the relationship between albuminuria and cardiac structure/function in heart failure with preserved ejection fraction (HFpEF). BACKGROUND: Albuminuria, a marker of endothelial dysfunction, has been associated with adverse cardiovascular outcomes in HFpEF. However, the relationship between albuminuria and cardiac structure/function in HFpEF has not been well studied. METHODS: We measured urinary albumin-to-creatinine ratio (UACR) and performed comprehensive echocardiography, including tissue Doppler imaging and right ventricular (RV) evaluation, in a prospective study of 144 patients with HFpEF. Multivariable-adjusted linear regression was used to determine the association between UACR and echocardiographic parameters. Cox proportional hazards analyses were used to determine the association between UACR and outcomes. RESULTS: The mean age was 66 ± 11 years, 62% were female, and 42% were African American. Higher UACR was associated with greater left ventricular mass, lower preload-recruitable stroke work, and lower global longitudinal strain. Higher UACR was also significantly associated with RV remodeling (for each doubling of UACR, RV wall thickness was 0.9 mm higher [95% confidence interval: 0.05 to 0.14 mm; p = 0.001, adjusted p = 0.01]) and worse RV systolic function (for each doubling of UACR, RV fractional area change was 0.56% lower [95% confidence interval: 0.14 to 0.98%; p = 0.01, adjusted p = 0.03]. The association between UACR and RV parameters persisted after the exclusion of patients with macroalbuminuria (UACR >300 mg/g). Increased UACR was also independently associated with worse outcomes. CONCLUSIONS: In HFpEF, increased UACR is a prognostic marker and is associated with increased RV and left ventricular remodeling and longitudinal systolic dysfunction. (Classification of Heart Failure With Preserved Ejection Fraction; NCT01030991).
Asunto(s)
Albuminuria/complicaciones , Insuficiencia Cardíaca/etiología , Remodelación Ventricular/fisiología , Anciano , Albuminuria/fisiopatología , Creatinina/orina , Femenino , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/orina , Humanos , Estimación de Kaplan-Meier , Masculino , Pronóstico , Estudios Prospectivos , Volumen Sistólico/fisiología , Disfunción Ventricular Izquierda/fisiopatología , Disfunción Ventricular Izquierda/orina , Disfunción Ventricular Derecha/fisiopatología , Disfunción Ventricular Derecha/orinaRESUMEN
BACKGROUND: Comorbidities are common in heart failure (HF), and the number of comorbidities has been associated with poor outcomes in HF patients. However, little is known about the effect of multiple comorbidities on cardiac mechanics, which could impact the pathogenesis of HF. We sought to determine the relationship between comorbidity burden and adverse cardiac mechanics. METHODS AND RESULTS: We performed speckle-tracking analysis on echocardiograms from the HyperGEN study (n=2150). Global longitudinal, circumferential, and radial strain, and early diastolic (e') tissue velocities were measured. We evaluated the association between comorbidity number and cardiac mechanics using linear mixed effects models to account for relatedness among subjects. The mean age was 51 ± 14 years, 58% were female, and 47% were African American. Dyslipidemia and hypertension were the most common comorbidities (61% and 58%, respectively). After adjusting for left ventricular (LV) mass index, ejection fraction, and several potential confounders, the number of comorbidities remained associated with all indices of cardiac mechanics except global circumferential strain (eg, ß=-0.32 [95% CI -0.44, -0.20] per 1-unit increase in number of comorbidities for global longitudinal strain; ß=-0.16 [95% CI -0.20, -0.11] for e' velocity; P ≤ 0.0001 for both comparisons). Results were similar after excluding participants with abnormal LV geometry (P<0.05 for all comparisons). CONCLUSIONS: Higher comorbidity burden is associated with worse cardiac mechanics, even in the presence of normal LV geometry. The deleterious effect of multiple comorbidities on cardiac mechanics may explain both the high comorbidity burden and adverse outcomes in patients who ultimately develop HF.
Asunto(s)
Insuficiencia Cardíaca/epidemiología , Negro o Afroamericano/estadística & datos numéricos , Comorbilidad , Estudios Transversales , Dislipidemias/epidemiología , Ecocardiografía Doppler , Femenino , Corazón/fisiopatología , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/fisiopatología , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatología , Humanos , Hipertensión/epidemiología , Interpretación de Imagen Asistida por Computador , Masculino , Persona de Mediana Edad , Factores de Riesgo , Volumen Sistólico/fisiología , Población Blanca/estadística & datos numéricosRESUMEN
BACKGROUND: Albuminuria is a marker of endothelial dysfunction and has been associated with adverse cardiovascular outcomes. The reasons for this association are unclear but may be attributable to the relationship between endothelial dysfunction and intrinsic myocardial dysfunction. METHODS AND RESULTS: In the Hypertension Genetic Epidemiology Network (HyperGEN) Study, a population- and family-based study of hypertension, we examined the relationship between urine albumin-to-creatinine ratio (UACR) and cardiac mechanics (n=1894, all of whom had normal left ventricular ejection fraction and wall motion). We performed speckle-tracking echocardiographic analysis to quantify global longitudinal, circumferential, and radial strain, and early diastolic (e') tissue velocities. We used E/e' ratio as a marker of increased left ventricular filling pressures. We used multivariable-adjusted linear mixed effect models to determine independent associations between UACR and cardiac mechanics. The mean age was 50±14 years, 59% were female, and 46% were black. Comorbidities were increasingly prevalent among higher UACR quartiles. Albuminuria was associated with global longitudinal strain, global circumferential strain, global radial strain, e' velocity, and E/e' ratio on unadjusted analyses. After adjustment for covariates, UACR was independently associated with lower absolute global longitudinal strain (multivariable-adjusted mean global longitudinal strain [95% confidence interval] for UACR Quartile 1 = 15.3 [15.0-15.5]% versus UACR Q4 = 14.6 [14.3-14.9]%, P for trend <0.001) and increased E/e' ratio (Q1 = 25.3 [23.5-27.1] versus Q4 = 29.0 [27.0-31.0], P=0.003). The association between UACR and global longitudinal strain was present even in participants with UACR < 30 mg/g (P<0.001 after multivariable adjustment). CONCLUSIONS: Albuminuria, even at low levels, is associated with adverse cardiac mechanics and higher E/e' ratio.
Asunto(s)
Albuminuria/epidemiología , Albuminuria/genética , Hipertensión/epidemiología , Hipertensión/genética , Disfunción Ventricular Izquierda/epidemiología , Disfunción Ventricular Izquierda/genética , Adulto , Presión Sanguínea , Comorbilidad , Ecocardiografía , Femenino , Tasa de Filtración Glomerular , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Volumen Sistólico , Disfunción Ventricular Izquierda/diagnóstico por imagen , Presión VentricularRESUMEN
RATIONALE: Chronic hypoxia induces pulmonary vascular remodeling, pulmonary hypertension, and right ventricular hypertrophy. At present, little is known about mechanisms driving these responses. Hypoxia-inducible factor-1α (HIF-1α) is a master regulator of transcription in hypoxic cells, up-regulating genes involved in energy metabolism, proliferation, and extracellular matrix reorganization. Systemic loss of a single HIF-1α allele has been shown to attenuate hypoxic pulmonary hypertension, but the cells contributing to this response have not been identified. OBJECTIVES: We sought to determine the contribution of HIF-1α in smooth muscle on pulmonary vascular and right heart responses to chronic hypoxia. METHODS: We used mice with homozygous conditional deletion of HIF-1α combined with tamoxifen-inducible smooth muscle-specific Cre recombinase expression. Mice received either tamoxifen or vehicle followed by exposure to either normoxia or chronic hypoxia (10% O2) for 30 days before measurement of cardiopulmonary responses. MEASUREMENTS AND MAIN RESULTS: Tamoxifen-induced smooth muscle-specific deletion of HIF-1α attenuated pulmonary vascular remodeling and pulmonary hypertension in chronic hypoxia. However, right ventricular hypertrophy was unchanged despite attenuated pulmonary pressures. CONCLUSIONS: These results indicate that HIF-1α in smooth muscle contributes to pulmonary vascular remodeling and pulmonary hypertension in chronic hypoxia. However, loss of HIF-1 function in smooth muscle does not affect hypoxic cardiac remodeling, suggesting that the cardiac hypertrophy response is not directly coupled to the increase in pulmonary artery pressure.
Asunto(s)
Hipertensión Pulmonar/metabolismo , Hipertrofia Ventricular Derecha/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Hipoxia/complicaciones , Músculo Liso Vascular/metabolismo , Arteria Pulmonar/metabolismo , Remodelación de las Vías Aéreas (Respiratorias) , Animales , Enfermedad Crónica , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/patología , Hipertrofia Ventricular Derecha/etiología , Hipertrofia Ventricular Derecha/patología , Hipoxia/metabolismo , Hipoxia/patología , Subunidad alfa del Factor 1 Inducible por Hipoxia/deficiencia , Masculino , Ratones , Ratones Noqueados , Músculo Liso Vascular/patología , Arteria Pulmonar/patología , Distribución AleatoriaRESUMEN
BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome associated with multiple pathophysiologic abnormalities, including left ventricular (LV) diastolic dysfunction, longitudinal LV systolic dysfunction, abnormal ventricular-arterial coupling, pulmonary hypertension, and right ventricular (RV) remodeling/dysfunction. However, the relative prognostic significance of each of these pathophysiologic abnormalities in HFpEF is unknown. METHODS AND RESULTS: We prospectively studied 419 patients with HFpEF using echocardiography and sphygmomanometry to assess HFpEF pathophysiologic markers. Cox proportional hazards analyses were used to determine the associations between pathophysiologic markers and outcomes. Mean age was 65±12 years; 62% were women; 39% were black; comorbidities were common; and study participants met published criteria for HFpEF. RV abnormalities were frequent: 28% had abnormal tricuspid annular plane systolic excursion, 15% had reduced RV fractional area change, and 34% had RV hypertrophy. During a median follow-up time of 18 months, 102 (24%) were hospitalized for HF and 175 (42%) experienced the composite end point of cardiovascular hospitalization or death. Decreased LV compliance, measured as reduced LV end-diastolic volume at an idealized LV end-diastolic pressure of 20 mm Hg (EDV20), and RV remodeling, as indicated by increased RV wall thickness, were the 2 pathophysiologic markers most predictive of worse outcomes: adjusted hazard ratio per 1 SD decrease in EDV20=1.39 (95% confidence interval [CI], 1.10-1.75; P=0.006), and hazard ratio per 1 SD increase in RV wall thickness=1.37 (95% CI, 1.16-1.61; P<0.001). These associations persisted after additional adjustment for markers of HF severity. By contrast, markers of LV relaxation, longitudinal LV systolic dysfunction, and ventricular-arterial coupling were not significantly associated with adverse outcomes. CONCLUSIONS: In patients with HFpEF, reduced LV compliance and RV remodeling are the strongest pathophysiologic predictors of adverse outcomes.
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Ecocardiografía Doppler/métodos , Insuficiencia Cardíaca/fisiopatología , Ventrículos Cardíacos/fisiopatología , Volumen Sistólico/fisiología , Función Ventricular Izquierda/fisiología , Remodelación Ventricular , Anciano , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/diagnóstico por imagen , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Masculino , Pronóstico , Estudios Prospectivos , Índice de Severidad de la EnfermedadRESUMEN
Although the development of abnormal myocardial mechanics represents a key step during the transition from hypertension to overt heart failure (HF), the underlying ultrastructural and cellular basis of abnormal myocardial mechanics remains unclear. We therefore investigated how changes in transverse (T)-tubule organization and the resulting altered intracellular Ca(2+) cycling in large cell populations underlie the development of abnormal myocardial mechanics in a model of chronic hypertension. Hearts from spontaneously hypertensive rats (SHRs; n = 72) were studied at different ages and stages of hypertensive heart disease and early HF and were compared with age-matched control (Wistar-Kyoto) rats (n = 34). Echocardiography, including tissue Doppler and speckle-tracking analysis, was performed just before euthanization, after which T-tubule organization and Ca(2+) transients were studied using confocal microscopy. In SHRs, abnormalities in myocardial mechanics occurred early in response to hypertension, before the development of overt systolic dysfunction and HF. Reduced longitudinal, circumferential, and radial strain as well as reduced tissue Doppler early diastolic tissue velocities occurred in concert with T-tubule disorganization and impaired Ca(2+) cycling, all of which preceded the development of cardiac fibrosis. The time to peak of intracellular Ca(2+) transients was slowed due to T-tubule disruption, providing a link between declining cell ultrastructure and abnormal myocardial mechanics. In conclusion, subclinical abnormalities in myocardial mechanics occur early in response to hypertension and coincide with the development of T-tubule disorganization and impaired intracellular Ca(2+) cycling. These changes occur before the development of significant cardiac fibrosis and precede the development of overt cardiac dysfunction and HF.
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Insuficiencia Cardíaca/fisiopatología , Hipertensión/fisiopatología , Miocardio/patología , Miocitos Cardíacos/ultraestructura , Sarcolema/ultraestructura , Animales , Presión Sanguínea , Calcio/metabolismo , Señalización del Calcio , Fibrosis/fisiopatología , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/patología , Frecuencia Cardíaca , Hipertensión/diagnóstico por imagen , Hipertensión/patología , Miocardio/metabolismo , Miocitos Cardíacos/metabolismo , Ratas , Ratas Endogámicas SHR , Ratas Wistar , UltrasonografíaRESUMEN
The treatment of heart failure (HF) is challenging and morbidity and mortality are high. The goal of this study was to determine if inhibition of the late Na(+) current with ranolazine during early hypertensive heart disease might slow or stop disease progression. Spontaneously hypertensive rats (aged 7 mo) were subjected to echocardiographic study and then fed either control chow (CON) or chow containing 0.5% ranolazine (RAN) for 3 mo. Animals were then restudied, and each heart was removed for measurements of t-tubule organization and Ca(2+) transients using confocal microscopy of the intact heart. RAN halted left ventricular hypertrophy as determined from both echocardiographic and cell dimension (length but not width) measurements. RAN reduced the number of myocytes with t-tubule disruption and the proportion of myocytes with defects in intracellular Ca(2+) cycling. RAN also prevented the slowing of the rate of restitution of Ca(2+) release and the increased vulnerability to rate-induced Ca(2+) alternans. Differences between CON- and RAN-treated animals were not a result of different expression levels of voltage-dependent Ca(2+) channel 1.2, sarco(endo)plasmic reticulum Ca(2+)-ATPase 2a, ryanodine receptor type 2, Na(+)/Ca(2+) exchanger-1, or voltage-gated Na(+) channel 1.5. Furthermore, myocytes with defective Ca(2+) transients in CON rats showed improved Ca(2+) cycling immediately upon acute exposure to RAN. Increased late Na(+) current likely plays a role in the progression of cardiac hypertrophy, a key pathological step in the development of HF. Early, chronic inhibition of this current slows both hypertrophy and development of ultrastructural and physiological defects associated with the progression to HF.
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Acetanilidas/farmacología , Señalización del Calcio/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Miocitos Cardíacos/efectos de los fármacos , Piperazinas/farmacología , Bloqueadores de los Canales de Sodio/farmacología , Canales de Sodio/efectos de los fármacos , Sodio/metabolismo , Animales , Canales de Calcio Tipo L/efectos de los fármacos , Canales de Calcio Tipo L/metabolismo , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Relación Dosis-Respuesta a Droga , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/prevención & control , Hipertensión/complicaciones , Hipertensión/diagnóstico por imagen , Hipertensión/metabolismo , Hipertensión/fisiopatología , Hipertrofia Ventricular Izquierda/etiología , Hipertrofia Ventricular Izquierda/metabolismo , Hipertrofia Ventricular Izquierda/fisiopatología , Hipertrofia Ventricular Izquierda/prevención & control , Masculino , Miocitos Cardíacos/metabolismo , Canal de Sodio Activado por Voltaje NAV1.5/efectos de los fármacos , Canal de Sodio Activado por Voltaje NAV1.5/metabolismo , Ranolazina , Ratas , Ratas Endogámicas SHR , Canal Liberador de Calcio Receptor de Rianodina/efectos de los fármacos , Canal Liberador de Calcio Receptor de Rianodina/metabolismo , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/metabolismo , Canales de Sodio/metabolismo , Intercambiador de Sodio-Calcio/efectos de los fármacos , Intercambiador de Sodio-Calcio/metabolismo , Factores de Tiempo , UltrasonografíaRESUMEN
Although concentric remodeling (CR) and concentric hypertrophy (CH) are common forms of left ventricular (LV) remodeling in heart failure with preserved ejection fraction (HFpEF), eccentric hypertrophy (EH) can also occur in these patients. However, clinical characteristics and outcomes of EH have not been well described in HFpEF. We prospectively studied 402 patients with HFpEF, divided into 4 groups based on LV structure: normal geometry (no LV hypertrophy [LVH] and relative wall thickness [RWT] ≤0.42); CR (no LVH and RWT >0.42); CH (LVH and RWT >0.42); and EH (LVH and RWT ≤0.42). We compared clinical, laboratory, echocardiographic, invasive hemodynamic, and outcome data among groups. Of 402 patients, 48 (12%) had EH. Compared with CH, patients with EH had lower systolic blood pressure and less renal impairment despite similar rates of hypertension. After adjustment for covariates, EH was associated with reduced LV contractility compared with CH: lower LVEF (ß coefficient = -3.2; 95% confidence interval [CI] -5.4 to -1.1%) and ratio of systolic blood pressure to end-systolic volume (ß coefficient = -1.0; 95% CI -1.5 to -0.5 mm Hg/ml). EH was also associated with increased LV compliance compared with CH (LV end-diastolic volume at an idealized LV end-diastolic pressure of 20 mm Hg ß coefficient = 14.2; 95% CI 9.4 to 19.1 ml). Despite these differences, EH and CH had similarly elevated cardiac filling pressures and equivalent adverse outcomes. In conclusion, the presence of EH denotes a distinct subset of HFpEF that is pathophysiologically similar to HF with reduced EF (HFrEF) and may benefit from HFrEF therapy.
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Insuficiencia Cardíaca/fisiopatología , Ventrículos Cardíacos/fisiopatología , Hipertrofia Ventricular Izquierda/epidemiología , Volumen Sistólico/fisiología , Remodelación Ventricular , Anciano , Progresión de la Enfermedad , Ecocardiografía , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/diagnóstico por imagen , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Hipertrofia Ventricular Izquierda/etiología , Hipertrofia Ventricular Izquierda/fisiopatología , Illinois/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Pronóstico , Estudios ProspectivosRESUMEN
BACKGROUND: Pulmonary hypertension (PH) occurs frequently and results in functional limitation in advanced COPD. Data regarding the functional consequence of PH in less severe COPD are limited. Whether echocardiographic evidence of right sided heart pathology is associated with functional outcomes in patients with non-severe COPD is unknown. METHODS: We evaluated pulmonary function, six minute walk distance, and echocardiography in 74 consecutive patients with non-severe COPD. We performed multivariable linear regression to evaluate the association between right heart echocardiographic parameters and six minute walk distance adjusting for lung function, age, sex, race, and BMI. MAIN RESULTS: The mean six minute walk distance was 324±106 meters. All subjects had preserved left ventricular (LV) systolic function (LV ejection fraction 62.3%±6.1%). 54.1% had evidence of some degree of diastolic dysfunction. 17.6% of subjects had evidence of right ventricular enlargement and 36.5% had right atrial enlargement. In univariate analysis RV wall thickness (ßâ=â-68.6; pâ=â0.002), log right atrial area (ßâ=â-297.9; pâ=â0.004), LV mass index (ßâ=â-1.3; pâ=â0.03), E/E' ratio (ßâ=â-5.5; pâ=â0.02), and degree of diastolic dysfunction (ßâ=â-42.8; pâ=â0.006) were associated with six minute walk distance. After adjustment for co-variables, the associations between right atrial area (log right atrial area ßâ=â-349.8; pâ=â0.003) and right ventricular wall thickness (ßâ=â-43.8; pâ=â0.04) with lower six minute walk distance remained significant independent of forced expiratory volume in one second (FEV1). LV mass index, E/E' ratio, and degree of diastolic dysfunction were not independent predictors of six minute walk distance. CONCLUSION: In patients with non-severe COPD right sided cardiac structural changes are associated with lower six minute walk distance independent of lung function. These findings may indicate that echocardiographic evidence of pulmonary hypertension is present in patients with non-severe COPD and has important functional consequences.