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OBJECTIVE: In severe aortic valve stenosis (AS), low left ventricular (LV) stroke volume has been associated with increased cardiovascular (CV) mortality, but this association has not been explored during progression of AS in a large prospective study. METHODS: In 1671 patients from the Simvastatin Ezetimibe in Aortic Stenosis (SEAS) study, the association of stroke volume indexed for body surface area (SVI) with major CV events during a median of 4.3-year follow-up was assessed in Cox and time-varying Cox regression analyses. Low SVI was defined as <35 mL/m2. RESULTS: Peak aortic jet velocity in the total study population was 3.1 ±0.7 m/s. Low SVI was found in 23% at baseline and associated with higher age, body mass index (BMI), heart rate and global LV load, and with lower mean aortic gradient, aortic valve area index, energy loss index, LV mass and ejection fraction and more often inconsistent AS grading (all p<0.05). A 5 mL/m2 lower SVI at baseline was associated with higher HRs of major CV events (n=544) (HR 1.09, 95% CI 1.05 to 1.13, p<0.001) and higher total mortality (n=147) (HR 1.08, 95% CI 1.01 to 1.16, p=0.038), independent of age, sex, atrial fibrillation, mean aortic gradient, LV ejection fraction, LV mass, BMI and study treatment. Adjusting for the same covariates, low SVI at baseline and in-study low SVI were also associated with increased rate of major CV events. CONCLUSION: In patients with AS in the SEAS study, lower baseline SVI was associated with higher HR of major CV events and total mortality independent of major confounders. TRIAL REGISTRATION NUMBER: NCT00092677: Results.
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Estenosis de la Válvula Aórtica/fisiopatología , Ezetimiba/uso terapéutico , Simvastatina/uso terapéutico , Volumen Sistólico/fisiología , Anciano , Anticolesterolemiantes/uso terapéutico , Estenosis de la Válvula Aórtica/tratamiento farmacológico , Estenosis de la Válvula Aórtica/mortalidad , Progresión de la Enfermedad , Método Doble Ciego , Quimioterapia Combinada , Ecocardiografía , Femenino , Alemania/epidemiología , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Masculino , Noruega/epidemiología , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Tasa de Supervivencia/tendencias , Suecia/epidemiología , Función Ventricular Izquierda/fisiologíaRESUMEN
Asymmetric interventricular septum hypertrophy (ASH) has been associated with increased perioperative morbidity and mortality in patients with severe, symptomatic aortic valve stenosis (AS). Less is known about the prognostic impact of ASH during progression of AS. Clinical, echocardiographic, and outcome data from 1,691 patients with initially asymptomatic, mostly moderate AS, participating in the Simvastatin Ezetimibe in Aortic Stenosis (SEAS) study was used. ASH was considered present if interventricular septum/posterior wall thickness ratio in end-diastole ≥1.5. The associations of ASH with hazard rate of ischemic cardiovascular events were tested in time-dependent Cox regression analyses. Based on the presence of ASH at study echocardiograms, the study population was grouped in to a no-ASH, nonpersistent ASH, persistent ASH, and new-onset ASH groups. During a median of 4.3 years of follow-up, ASH persisted or developed in 17% of patients. Persistent or new-onset ASH was characterized by higher left ventricular mass index and ejection fraction at baseline (both p <0.05) but not with female gender or hypertension. In time-varying Cox regression analyses adjusting for these confounders, persistent or new-onset ASH was associated with higher hazard rate of ischemic cardiovascular events (hazard rate 1.45; 95% confidence interval 1.09 to 1.91, p = 0.01), in particular coronary artery bypass grafting (hazard rate 1.69; 95% confidence interval 1.17 to 2.47; p = 0.006), whereas no association with increased mortality was found. In conclusion, in patients with AS without diabetes or known renal or cardiovascular disease participating in the SEAS study, persistent or new-onset ASH during progression of AS was associated with higher rate of ischemic cardiovascular events.
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Estenosis de la Válvula Aórtica/complicaciones , Hipertrofia Ventricular Izquierda/complicaciones , Isquemia Miocárdica/etiología , Anciano , Anciano de 80 o más Años , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/tratamiento farmacológico , Método Doble Ciego , Ecocardiografía , Femenino , Humanos , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Hipertrofia Ventricular Izquierda/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/diagnóstico por imagen , Pronóstico , Estudios ProspectivosRESUMEN
BACKGROUND: Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory marker associated with subclinical cardiovascular damage and cardiovascular events. Whether suPAR is of prognostic value in asymptomatic patients with aortic stenosis (AS) remains unknown. METHODS: Plasma suPAR levels were measured in 1503 patients with a mean age of 68 years who were recruited in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Cox regression analysis was performed to evaluate associations between suPAR and the composite end points of ischemic cardiovascular events (ICEs), aortic valve events (AVEs), cardiovascular and all-cause mortality after adjusting for traditional cardiovascular risk factors, and allocation to treatment. RESULTS: The multivariate adjusted hazard ratio (HR) (95% confidence interval [CI]) per unit log2 ng/mL increase in suPAR was HR, 1.5; 95% CI, 1.2-1.9; P = 0.002 for ICEs; HR, 1.2; 95% CI, 0.9-1.5; P = 0.071) for AVEs; HR, 2.0; 95% CI, 1.2-3.3; P = 0.007) for cardiovascular mortality, and HR, 2.0; 95% CI, 1.4-2.9; P < 0.001 for all-cause mortality. CONCLUSIONS: In patients with mild-moderate AS, suPAR is independently associated with the incidence of ICEs, cardiovascular mortality, and all-cause mortality.
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Estenosis de la Válvula Aórtica , Receptores del Activador de Plasminógeno Tipo Uroquinasa/sangre , Anciano , Estenosis de la Válvula Aórtica/sangre , Estenosis de la Válvula Aórtica/complicaciones , Estenosis de la Válvula Aórtica/diagnóstico , Estenosis de la Válvula Aórtica/mortalidad , Enfermedades Asintomáticas , Biomarcadores/sangre , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/epidemiología , Isquemia Miocárdica/etiología , Valor Predictivo de las Pruebas , Pronóstico , Modelos de Riesgos Proporcionales , Reproducibilidad de los Resultados , Medición de Riesgo , Factores de RiesgoRESUMEN
Objective To investigate relations between inflammation and aortic valve stenosis (AS) by measuring high-sensitivity C-reactive protein, at baseline (hsCRP0) and after 1 year (hsCRP1) and exploring associations with aortic valve replacement (AVR). Design We examined 1423 patients from the Simvastatin and Ezetimibe in Aortic Stenosis study. Results During first year of treatment, hsCRP was reduced both in patients later receiving AVR (2.3 [0.9-4.9] to 1.8 [0.8-5.4] mg/l, p < 0.001) and not receiving AVR (1.90 [0.90-4.10] to 1.3 [0.6-2.9] mg/l, p < 0.001). In Cox-regression analyses, hsCRP1 predicted later AVR (HR = 1.17, p < 0.001) independently of hsCRP0 (HR = 0.96, p = 0.33), aortic valve area (AVA) and other risk factors. A higher rate of AVR was observed in the group with high hsCRP0 and an increase during the first year (AVRhighCRP0CRP1inc = 47.3% versus AVRhighCRP0CRP1dec = 27.5%, p < 0.01). The prognostic benefit of a 1-year reduction in hsCRP was larger in patients with high versus low hsCRP0 eliminating the difference in incidence of AVR between high versus low hsCRP0 (AVRhighCRP0CRP1dec = 27.5% versus AVRlowCRP0CRP1dec = 25.8%, p = 0.66) in patients with reduced hsCRP during the first year. Conclusions High hsCRP1 or an increase in hsCRP during the first year of follow-up predicted later AVR independently of AVA, age, gender and other risk factors, although no significant improvement in C-statistics was observed.
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Estenosis de la Válvula Aórtica , Válvula Aórtica , Proteína C-Reactiva/análisis , Implantación de Prótesis de Válvulas Cardíacas/métodos , Inflamación/sangre , Anciano , Anciano de 80 o más Años , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/sangre , Estenosis de la Válvula Aórtica/diagnóstico , Estenosis de la Válvula Aórtica/fisiopatología , Estenosis de la Válvula Aórtica/cirugía , Ecocardiografía/métodos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Factores de Riesgo , Índice de Severidad de la Enfermedad , Volumen SistólicoRESUMEN
Recent American College of Cardiology/American Heart Association guidelines on statin initiation on the basis of total atherosclerotic cardiovascular disease risk argue that the preventive effect of statins on cardiovascular events outweigh the side effects, although this is controversial. Studies indicate a possible effect of statin therapy on reducing risk of lens opacities. However, the results are conflicting. The Simvastatin and Ezetimibe in Aortic Stenosis study (NCT00092677) enrolled 1,873 patients with asymptomatic aortic stenosis and no history of diabetes, coronary heart disease, or other serious co-morbidities were randomized (1:1) to double-blind 40 mg simvastatin plus 10 mg ezetimibe versus placebo. The primary end point in this substudy was incident cataract. Univariate and multivariate Cox models were used to analyze: (1) if the active treatment reduced the risk of the primary end point and (2) if time-varying low-density lipoproteins (LDL) cholesterol lowering (annually assessed) was associated with less incident cataract per se. During an average follow-up of 4.3 years, 65 patients (3.5%) developed cataract. Mean age at baseline was 68 years and 39% were women. In Cox multivariate analysis adjusted for age, gender, prednisolone treatment, smoking, baseline LDL cholesterol and high sensitivity C-reactive protein; simvastatin plus ezetimibe versus placebo was associated with 44% lower risk of cataract development (hazard ratio 0.56, 95% confidence interval 0.33 to 0.96, p = 0.034). In a parallel analysis substituting time-varying LDL-cholesterol with randomized treatment, lower intreatment LDL-cholesterol was in itself associated with lower risk of incident cataract (hazard ratio 0.78 per 1 mmol/ml lower total cholesterol, 95% confidence interval 0.64 to 0.93, p = 0.008). In conclusion, randomized treatment with simvastatin plus ezetimibe was associated with a 44% lower risk of incident cataract development. This effect should perhaps be considered in the risk-benefit ratio of statin treatment.
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Estenosis de la Válvula Aórtica/tratamiento farmacológico , Catarata/etiología , LDL-Colesterol/sangre , Ezetimiba/uso terapéutico , Simvastatina/uso terapéutico , Anciano , Anciano de 80 o más Años , Anticolesterolemiantes/uso terapéutico , Estenosis de la Válvula Aórtica/sangre , Estenosis de la Válvula Aórtica/complicaciones , Catarata/epidemiología , LDL-Colesterol/efectos de los fármacos , Dinamarca/epidemiología , Método Doble Ciego , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Noruega/epidemiología , Factores de Riesgo , Suecia/epidemiología , Reino Unido/epidemiología , Estados Unidos/epidemiologíaRESUMEN
Surgical centres of excellence should include multidisciplinary teams with specialist expertise in imaging, clinical assessment and surgery for patients with heart valve disease. There should be structured training programmes for the staff involved in the periprocedural care of the patient and these should be overseen by national or international professional societies. Good results are usually associated with high individual and centre volumes, but this relationship is complex. Results of surgery should be published by centre and should include rates of residual regurgitation for mitral repairs and reoperation rates matched to the preoperative pathology and risk.
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AIMS: To assess the prognostic importance of high-sensitive C reactive protein (hsCRP) in patients with mild to moderate aortic valve stenosis during placebo or simvastatin/ezetimibe treatment in Simvastatin and Ezetimibe in Aortic Stenosis (SEAS). METHODS AND RESULTS: In 1620 SEAS patients, we measured lipids and hsCRP at baseline and after 1â year of treatment and registered during 4â years of follow-up major cardiovascular events (MCE) composed of ischaemic cardiovascular events (ICE) and aortic valve-related events (AVE). Simvastatin/ezetimibe reduced low-density lipoprotein cholesterol (3.49 (2.94 to 4.15) to 1.32 (1.02 to 1.69) vs 3.46 (2.92 to 4.08) to 3.34 (2.81 to 3.92)â mmol/L) and hsCRP (2.1 (0.9 to 4.1) to 1.2 (0.6 to 2.4) vs 2.2 (0.9 to 4.9) to 1.8 (0.85 to 4.35)â mg/L, all p<0.05) during the first year of treatment. In multivariable Cox regression analysis adjusting for traditional risk factors and baseline hsCRP, ICE was associated with a 1-year increase of hsCRP (HR=1.19 (95% CI 1.12 to 1.25), p<0.001) but not with active treatment (HRTreatment=0.86 (0.67 to 1.13), p=0.28). Patients in the top quartile of baseline hsCRP versus the rest were associated with a higher risk of MCE (HR=1.34(1.09 to 1.64), p=0.02). The prognostic benefit of reduction in hsCRP after 1â year was significantly larger (p<0.01 for interaction) in patients with high versus low baseline hsCRP; hence, a reduction in hsCRP abolished the difference in incidence of MCE between high versus low baseline hsCRP in patients with reduced hsCRP (31.1 vs 31.9%, NS) in contrast to patients with increased hsCRP. CONCLUSIONS: The treatment-associated reduction in ICE was in part related to a reduction in hsCRP but not in lipids. hsCRP reduction was associated with less MCE, especially in patients with high baseline hsCRP. TRIAL REGISTRATION: NCT00092677.
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OBJECTIVE: Women with severe aortic valve stenosis (AS) have better LV systolic function and more concentric LV geometry than their male counterparts. However, sex differences in cardiovascular (CV) outcome during progression of AS have not been reported from a longitudinal prospective study. METHODS: Doppler echocardiography and CV events were recorded during a median of 4.0â years in 979 men and 632 women aged 28-86 (mean 67±10) years in the Simvastatin Ezetimibe in Aortic Stenosis (SEAS) study. LV systolic function was assessed by EF and midwall shortening (MWS). Study outcomes were AS-related events, ischaemic CV events and total mortality. RESULTS: The annular cumulative incidence of AS events, ischaemic CV events and death was 8.1%, 3.4% and 2.8% in women, and 8.9%, 4.4% and 2.4% in men, respectively. Women and men had similar AS progression rate whether measured by peak jet velocity, mean gradient or valve area. In multivariate analyses, female sex independently predicted less reduction in LV MWS and EF during follow-up (both p<0.05). In time-varying Cox analyses, women had a 40% lower rate of ischaemic CV events (95% CI 21% to 54%), in particular, more than 50% lower rate of stroke and coronary artery bypass grafting, and a 31% lower all-cause mortality (95% CI 1% to 51%), independent of active study treatment, age and hypertension, as well as time-varying valve area, low systolic function and abnormal LV geometry. AS event rate did not differ by sex. CONCLUSIONS: In the SEAS study, women and men had similar rates of AS progression and AS-related events. However, women had lower total mortality and ischaemic CV event rate than men independent of confounders. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT00092677.
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Estenosis de la Válvula Aórtica/tratamiento farmacológico , Simvastatina/uso terapéutico , Función Ventricular Izquierda/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Estenosis de la Válvula Aórtica/mortalidad , Estenosis de la Válvula Aórtica/fisiopatología , Progresión de la Enfermedad , Método Doble Ciego , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Masculino , Persona de Mediana Edad , Noruega/epidemiología , Pronóstico , Distribución por Sexo , Factores Sexuales , Tasa de Supervivencia/tendencias , Sístole , Resultado del TratamientoRESUMEN
OBJECTIVE: To evaluate the usefulness of velocity ratio (VR) in patients with low gradient severe aortic stenosis (LGSAS) and preserved EF. BACKGROUND: LGSAS despite preserved EF represents a clinically challenging entity. Reliance on mean pressure gradient (MPG) may underestimate stenosis severity as has been reported in the context of paradoxical low flow, LGSAS. On the other hand, grading of stenosis severity by aortic valve area (AVA) may overrate stenosis severity due to erroneous underestimation of LV outflow tract (LVOT) diameter, small body size or inconsistencies in cut-off values for severe stenosis. We hypothesised that VR may have conceptual advantages over MPG and AVA, predict clinical outcomes and thereby be useful in the management of patients with LGSAS. METHODS: Patients from the prospective Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study with an AVA<1.0â cm(2), MPG≤40â mmâ Hg and EF≥55% and asymptomatic at baseline were stratified according to VR with a cut-off value of 0.25. Outcomes were evaluated according to aortic valve-related events and cardiovascular death. RESULTS: Of 435 patients with LGSAS, 197 (45%) had VR<0.25 suggesting severe and 238 (55%) had VR≥0.25 suggesting non-severe stenosis. Aortic valve-related events (mean follow-up 42±14â months) were more frequent in patients with VR<0.25 (57% vs 41%; p<0.001) as was cardiovascular death within the first 24â months (p<0.05). In multivariable Cox regression analysis, MPG was the strongest independent predictor of aortic valve events (p<0.001) followed by VR (p<0.02). Adjusting AVA by VR increased predictive accuracy for aortic valve events (area under the receiver operating curve 0.62 (95% CI 0.57 to 0.67) vs 0.56 (95% CI 0.51 to 0.61) for AVA, p=0.02) with net reclassification improvement calculated at 0.36 (95% CI 0.17 to 0.54, p<0.001). VR did not improve the prediction of clinical events by MPG. CONCLUSIONS: In the difficult setting of LGSAS, VR shows a strong association with valve-related events and-although not outperforming MPG-may be particularly useful in guiding clinical management. TRIAL REGISTRATION NUMBER: NCT00092677.
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Estenosis de la Válvula Aórtica/fisiopatología , Anciano , Anticolesterolemiantes/uso terapéutico , Estenosis de la Válvula Aórtica/tratamiento farmacológico , Estenosis de la Válvula Aórtica/mortalidad , Azetidinas/uso terapéutico , Velocidad del Flujo Sanguíneo/fisiología , Ecocardiografía , Ezetimiba , Femenino , Insuficiencia Cardíaca/etiología , Humanos , Masculino , Estudios Prospectivos , Curva ROC , Simvastatina/uso terapéutico , Volumen Sistólico/fisiologíaRESUMEN
The prevalence of cardiovascular diseases (CVDs) in women of childbearing age is rising. The successes in medical and surgical treatment of congenital heart disease have led to an increasing number of women at childbearing age presenting with problems of treated congenital heart disease. Furthermore, in developing countries and in immigrants from these countries, rheumatic valvular heart disease still plays a significant role in young women. Increasing age of pregnant women and increasing prevalence of atherosclerotic risk factors have led to an increase in women with coronary artery disease at pregnancy. Successful management of pregnancy in women with CVDs requires early diagnosis, a thorough risk stratification, and appropriate management by a multidisciplinary team of obstetricians, cardiologists, anesthesiologists, and primary care physicians. The following review is based on the recent European guidelines on the management of CVDs during pregnancy, which aim at providing concise and simple recommendations for these challenging problems.
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Manejo de la Enfermedad , Complicaciones Cardiovasculares del Embarazo/diagnóstico , Complicaciones Cardiovasculares del Embarazo/terapia , Europa (Continente) , Femenino , Humanos , EmbarazoRESUMEN
We tested the hypothesis that the disproportionate increase of body surface area in obesity may lead to the overestimation of aortic stenosis (AS) severity when the aortic valve area (AVA) is indexed (AVAI) for body surface area in 1,524 patients enrolled in the Simvastatin and Ezetimibe in AS study. Obesity was defined as a body mass index of ≥30 kg/m(2). Peak aortic jet velocity, mean aortic gradient, AVA, and energy loss (EL) did not differ, although AVAI and EL indexed (ELI) for body surface area were significantly smaller in the obese group (n = 321) compared with the nonobese (n = 1,203) group (both p <0.05). Severe AS by AVAI (<0.6 cm(2)/m(2)) but nonsevere by AVA (>1.0 cm(2); AVAI/AVA discordance) was found in 15% of the patients, whereas severe AS by ELI (<0.6 cm(2)/m(2)) but nonsevere by EL (>1.0 cm(2); ELI/EL discordance) was found in 9% of the patients. Obesity was associated with a 2.4-fold higher prevalence of AVAI/AVA discordance and a 1.6-fold higher prevalence of ELI/EL discordance. Discordant grading was also associated with male gender, larger body size, higher mean aortic gradient, and stroke volume (all p <0.05). During a median follow-up of 4.3 years, 419 patients were referred for aortic valve replacement and 177 patients died or were hospitalized because of heart failure. In the Cox regression analyses, AVAI/AVA discordance was associated with a 28% higher rate of aortic valve replacement (p <0.05) but did not predict the rate of combined death and hospitalization for heart failure. In conclusion, using AVAI and ELI for the grading of stenosis in patients with obesity may lead to overestimation of true AS severity.
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Estenosis de la Válvula Aórtica , Obesidad/complicaciones , Índice de Severidad de la Enfermedad , Anciano , Anciano de 80 o más Años , Estenosis de la Válvula Aórtica/complicaciones , Estenosis de la Válvula Aórtica/diagnóstico , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Ecocardiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis de RegresiónRESUMEN
BACKGROUND: To account for differences in body size in patients with aortic stenosis, aortic valve area (AVA) is divided by body surface area (BSA) to calculate indexed AVA (AVAindex). Cut-off values for severe stenosis are <1.0 cm2 for AVA and <0.6 cm2/m2 for AVAindex. OBJECTIVE: To investigate the influence of indexation on the prevalence of severe aortic stenosis and on the predictive accuracy regarding clinical outcome. METHODS: Echocardiographic and anthropometric data from a retrospective cohort of 2843 patients with aortic stenosis (jet velocity >2.5 m/s) and from 1525 patients prospectively followed in the simvastatin and ezetimibe in aortic stenosis (SEAS) trial were analysed. RESULTS: The prevalence of severe stenosis increased with the AVAindex criterion compared to AVA from 71% to 80% in the retrospective cohort, and from 29% to 44% in SEAS (both p<0.001). Overall, the predictive accuracy for aortic valve events was virtually identical for AVA and AVAindex in the SEAS population (mean follow-up of 46 months; area under the receiver operating characteristic curve: 0.67 (95% CI 0.64 to 0.70) vs. 0.68 (CI 0.65 to 0.71) (NS). However, 213 patients additionally categorised as severe by AVAindex experienced significantly less valve related events than those fulfilling only the AVA criterion (p<0.001). CONCLUSIONS: Indexing AVA by BSA (AVAindex) significantly increases the prevalence of patients with criteria for severe stenosis by including patients with a milder degree of the disease without improving the predictive accuracy for aortic valve related events.
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Estenosis de la Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/diagnóstico por imagen , Ecocardiografía Doppler/métodos , Adulto , Anciano , Anciano de 80 o más Años , Válvula Aórtica/fisiopatología , Estenosis de la Válvula Aórtica/epidemiología , Estenosis de la Válvula Aórtica/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Reproducibilidad de los Resultados , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Suiza/epidemiología , Adulto JovenRESUMEN
Increased life expectancy has led to a higher prevalence of calcific aortic valve disease. Both ends of the disease spectrum-sclerosis of the aortic valve without hemodynamic obstruction and the late stage of aortic valve stenosis (AS)-have been associated with increased morbidity and mortality. This raises the question of the prognostic contribution of atherosclerotic diseases and other comorbidities as opposed to the hemodynamic effect of obstructive AS. Hence, the evaluation of asymptomatic patients with mild or moderate AS without comorbidities is of major interest. In the Simvastatin and Ezetimibe in Aortic Stenosis study, with the exception of hypertension, comorbidities were excluded, thus allowing an analysis of the effect of pure AS as well as the effect of hypertension on the progression and outcome of AS. We discuss the results that emerged from this large European prospective study and relate these to the published literature.
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Estenosis de la Válvula Aórtica/tratamiento farmacológico , Válvula Aórtica/patología , Calcinosis/tratamiento farmacológico , Anticolesterolemiantes/uso terapéutico , Estenosis de la Válvula Aórtica/diagnóstico , Estenosis de la Válvula Aórtica/epidemiología , Azetidinas/uso terapéutico , Calcinosis/diagnóstico , Calcinosis/epidemiología , Comorbilidad , Progresión de la Enfermedad , Quimioterapia Combinada , Ezetimiba , Humanos , Hipertensión/epidemiología , Pronóstico , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Simvastatina/uso terapéutico , Resultado del TratamientoRESUMEN
OBJECTIVES: This study investigated whether overweight and obesity impacted outcome in patients with aortic valve stenosis (AS). BACKGROUND: Increased body mass index (BMI) is a strong predictor of higher cardiovascular (CV) morbidity and mortality in the general population but not among patients undergoing heart surgery. METHODS: Cardiovascular events in 1,664 patients with initially asymptomatic AS were recorded during a mean of 4.3 years of follow-up in the SEAS (Simvastatin Ezetimibe in Aortic Stenosis) study. Patients were grouped according to baseline BMI class. RESULTS: Overweight (n = 737) and obese patients (n = 334) had higher prevalence of hypertension, more abnormal left ventricular geometry, and lower stress-corrected midwall shortening throughout the study compared with normal weight patients (all p < 0.01). The AS progression rate did not differ between BMI classes. In univariate Cox regression, overweight was associated with a 17% to 22% lower rate of AS-related (p = 0.04) and ischemic CV events (p = 0.05). In multivariate analyses, adjusting for AS severity and differences in baseline characteristics, overweight had no significant influence on the rate of ischemic CV or AS-related events, whereas overweight and obesity had 46% and 67% higher rate of total mortality and 42% and 69% higher rate of combined hospital stay for heart failure and death from any cause, respectively, compared with normal weight patients (all p < 0.05). CONCLUSIONS: In patients with initially asymptomatic AS participating in the SEAS study, overweight and obesity did not influence AS progression or rate of AS-related or ischemic CV events but were both associated with increased mortality.
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Estenosis de la Válvula Aórtica/epidemiología , Obesidad/epidemiología , Sobrepeso/epidemiología , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/epidemiología , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Hipertensión/epidemiología , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Prospectivos , Ultrasonografía , Función Ventricular IzquierdaAsunto(s)
Instituciones Cardiológicas/normas , Cardiología/normas , Atención a la Salud/normas , Enfermedades de las Válvulas Cardíacas/terapia , Atención Ambulatoria/organización & administración , Atención Ambulatoria/normas , Instituciones de Atención Ambulatoria/normas , Cardiología/organización & administración , Competencia Clínica/normas , Humanos , Mejoramiento de la CalidadRESUMEN
INTRODUCTION: Valvuloarterial impedance (Zva) is a measure of global (combined valvular and arterial) load opposing left ventricular (LV) ejection in aortic stenosis (AS). The present study identified covariates and tested the prognostic significance of global LV load in patients with asymptomatic AS. METHODS: 1418 patients with mild-moderate, asymptomatic AS in the Simvastatin Ezetimibe in Aortic Stenosis (SEAS) study were followed for a mean of 43±14 months during randomized, placebo-controlled treatment with combined simvastatin 40 mg and ezetimibe 10 mg daily. High global LV load was defined as Zva >5 mm Hg/ml/m2. The impact of baseline global LV load on rate of major cardiovascular (CV) events, aortic valve events and total mortality was assessed in Cox regression models reporting hazard ratio (HR) and 95% Confidence Intervals (CI). RESULTS: High global LV load was found in 18% (n=252) of patients and associated with female gender, higher age, hypertension, more severe AS and lower ejection fraction (all p<0.05). A total of 476 major CV events, 444 aortic valve events and 132 deaths occurred during follow-up. In multivariate Cox regression analyses, high global LV load predicted higher rate of major CV events (HR 1.35 [95% CI 1.08-1.71], P=0.010) and aortic valve events (HR 1.41 [95% CI 1.12-1.79], P=0.004) independent of hypertension, LV ejection fraction, female gender, age, abnormal LV geometry and AS severity, but failed to predict mortality. CONCLUSION: In asymptomatic AS, assessment of global LV load adds complementary information on prognosis to that provided by hypertension or established prognosticators like AS severity and LV ejection fraction.
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Estenosis de la Válvula Aórtica/diagnóstico , Estenosis de la Válvula Aórtica/fisiopatología , Función Ventricular Izquierda/fisiología , Anciano , Anticolesterolemiantes/uso terapéutico , Estenosis de la Válvula Aórtica/tratamiento farmacológico , Azetidinas/uso terapéutico , Presión Sanguínea , Método Doble Ciego , Ezetimiba , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Factores de Riesgo , Simvastatina/uso terapéutico , Volumen Sistólico/fisiologíaRESUMEN
The impact of hypertension on left ventricular structure and outcome during progression of aortic valve stenosis has not been reported from a large prospective study. Data from 1616 patients with asymptomatic aortic stenosis randomized to placebo-controlled treatment with combined simvastatin and ezetimibe in the Simvastatin Ezetimibe in Aortic Stenosis Study were used. The primary study end point included combined cardiovascular death, aortic valve events, and ischemic cardiovascular events. Hypertension was defined as history of hypertension or elevated baseline blood pressure. Left ventricular hypertrophy was defined as left ventricular mass/height(2.7) ≥ 46.7 g/m(2.7) in women and ≥ 49.2 g/m(2.7) in men and concentric geometry as relative wall thickness ≥ 0.43. Baseline peak aortic jet velocity and aortic stenosis progression rate did not differ between hypertensive (n = 1340) and normotensive (n = 276) patients. During 4.3 years of follow-up, the prevalence of concentric left ventricular hypertrophy increased 3 times in both groups. Hypertension predicted 51% higher incidence of abnormal LV geometry at final study visit independent of other confounders (P<0.01). In time-varying Cox regression, hypertension did not predict increased rate of the primary study end point. However, hypertension was associated with a 56% higher rate of ischemic cardiovascular events and a 2-fold increased mortality (both P<0.01), independent of aortic stenosis severity, abnormal left ventricular geometry, in-treatment systolic blood pressure, and randomized study treatment. No impact on aortic valve replacement was found. In conclusion, among patients with initial asymptomatic mild-to-moderate aortic stenosis, hypertension was associated with more abnormal left ventricular structure and increased cardiovascular morbidity and mortality.
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Estenosis de la Válvula Aórtica/tratamiento farmacológico , Azetidinas/uso terapéutico , Hipertensión/complicaciones , Simvastatina/uso terapéutico , Anciano , Anciano de 80 o más Años , Anticolesterolemiantes/uso terapéutico , Antihipertensivos/uso terapéutico , Estenosis de la Válvula Aórtica/complicaciones , Presión Sanguínea/efectos de los fármacos , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/diagnóstico por imagen , Quimioterapia Combinada , Ecocardiografía , Ezetimiba , Femenino , Humanos , Hipertensión/fisiopatología , Hipertrofia Ventricular Izquierda/complicaciones , Hipertrofia Ventricular Izquierda/diagnóstico , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Medición de Riesgo/estadística & datos numéricos , Factores de RiesgoRESUMEN
AIMS: Risk scores provide an important contribution to clinical decision-making, but their validity has been questioned in patients with valvular heart disease (VHD), since current scores have been mainly derived and validated in adults undergoing coronary bypass surgery. The Working Group on Valvular Heart Disease of the European Society of Cardiology reviewed the performance of currently available scores when applied to VHD, in order to guide clinical practice and future development of new scores. METHODS AND RESULTS: The most widely used risk scores (EuroSCORE, STS, and Ambler score) were reviewed, analysing variables included and their predictive ability when applied to patients with VHD. These scores provide relatively good discrimination, i.e. a gross estimation of risk category, but cannot be used to estimate the exact operative mortality in an individual patient because of unsatisfactory calibration. CONCLUSION: Current risk scores do not provide a reliable estimate of exact operative mortality in an individual patient with VHD. They should therefore be interpreted with caution and only used as part of an integrated approach, which incorporates other patient characteristics, the clinical context, and local outcome data. Future risk scores should include additional variables, such as cognitive and functional capacity and be prospectively validated in high-risk patients. Specific risk models should also be developed for newer interventions, such as transcatheter aortic valve implantation.