RESUMEN
OBJECTIVE: Calcium metabolism has long been implicated in aortic stenosis (AS). Studies assessing the long-term safety of oral calcium and/or vitamin D in AS are scarce yet imperative given the rising use among an elderly population prone to deficiency. We sought to identify the associations between supplemental calcium and vitamin D with mortality and progression of AS. METHODS: In this retrospective longitudinal study, patients aged ≥60 years with mild-moderate native AS were selected from the Cleveland Clinic Echocardiography Database from 2008 to 2016 and followed until 2018. Groups were stratified into no supplementation, supplementation with vitamin D alone and supplementation with calcium±vitamin D. The primary outcomes were mortality (all-cause, cardiovascular (CV) and non-CV) and aortic valve replacement (AVR), and the secondary outcome was AS progression by aortic valve area and peak/mean gradients. RESULTS: Of 2657 patients (mean age 74 years, 42% women) followed over a median duration of 69 months, 1292 (49%) did not supplement, 332 (12%) took vitamin D alone and 1033 (39%) supplemented with calcium±vitamin D. Calcium±vitamin D supplementation was associated with a significantly higher risk of all-cause mortality (absolute rate (AR)=43.0/1000 person-years; HR=1.31, 95% CI (1.07 to 1.62); p=0.009), CV mortality (AR=13.7/1000 person-years; HR=2.0, 95% CI (1.31 to 3.07); p=0.001) and AVR (AR=88.2/1000 person-years; HR=1.48, 95% CI (1.24 to 1.78); p<0.001). Any supplementation was not associated with longitudinal change in AS parameters in a linear mixed-effects model. CONCLUSIONS: Supplemental calcium with or without vitamin D is associated with lower survival and greater AVR in elderly patients with mild-moderate AS.
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Estenosis de la Válvula Aórtica , Implantación de Prótesis de Válvulas Cardíacas , Anciano , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Calcio , Femenino , Humanos , Estudios Longitudinales , Masculino , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Vitamina D , VitaminasRESUMEN
Clinical studies suggest increased arrhythmia risk associated with cell therapy for myocardial infarction (MI); however, the underlying mechanisms are poorly understood. We hypothesize that the degree of electrical viability in the infarct and border zone associated with skeletal myoblast (SKMB) or mesenchymal stem cell (MSC) therapy will determine arrhythmia vulnerability in the whole heart. Within 24 h of LAD ligation in rats, 2 million intramyocardially injected SKMB (n=6), intravenously infused MSC (n=7), or saline (n=7) was administered. One month after MI, cardiac function was determined and novel optical mapping techniques were used to assess electrical viability and arrhythmia inducibility. Shortening fraction was greater in rats receiving SKMB (17.8%+/-5.3%, p=0.05) or MSC (17.6%+/-3.0%, p<0.01) compared to MI alone (10.1%+/-2.2%). Arrhythmia inducibility score was significantly greater in SKMB (2.8+/-0.2) compared to MI (1.4+/-0.5, p=0.05). Inducibility score for MSC (0.6+/-0.4) was significantly lower than SKMB (p=0.01) and tended to be lower than MI. Optical mapping revealed that MSC therapy preserved electrical viability and impulse propagation in the border zone, but SKMB did not. In addition, injected SKMBs were localized to discrete cell clusters where connexin expression was absent. In contrast, infused MSCs engrafted in a more homogeneous pattern and expressed connexin proteins. Even though both MSC and SKMB therapy improved cardiac function following MI in rat, SKMB therapy significantly increased arrhythmia inducibility while MSC therapy tended to lower inducibility. In addition, only MSC therapy was associated with enhanced electrical viability, diffuse engraftment, and connexin expression, which may explain the differences in arrhythmia inducibility.
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Trasplante de Células Madre Mesenquimatosas , Mioblastos Esqueléticos/trasplante , Infarto del Miocardio/terapia , Recuperación de la Función , Animales , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/patología , Arritmias Cardíacas/fisiopatología , Arritmias Cardíacas/terapia , Supervivencia Celular , Técnicas Electrofisiológicas Cardíacas , Supervivencia de Injerto , Sistema de Conducción Cardíaco/patología , Sistema de Conducción Cardíaco/fisiopatología , Mioblastos Esqueléticos/metabolismo , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Infarto del Miocardio/fisiopatología , Ratas , Trasplante HomólogoRESUMEN
BACKGROUND: It has been shown that transient increase in left ventricular stiffness, assessed by Doppler-derived early filling deceleration time, occurs during the first 24 to 48 hours after myocardial infarction but returns to normal within several days. It has been reported that hyperbaric oxygen treatment has a favorable effect on left ventricular systolic function in patients with acute myocardial infarction treated with thrombolysis. However, there are no data on the effects of hyperbaric oxygen on diastolic function after myocardial infarction. METHODS: To assess acute and short-term effects of hyperbaric oxygen on left ventricular chamber stiffness, we studied 74 consecutive patients with first acute myocardial infarction who were randomly assigned to treatment with hyperbaric oxygen combined with streptokinase or streptokinase alone. After thrombolysis, patients in the hyperbaric oxygen group received 100% oxygen at 2 atm for 60 minutes in a hyperbaric chamber. All patients underwent 2-dimensional and Doppler echocardiography 1 (after thrombolysis), 2, 3, 7, 21, and 42 days after myocardial infarction. RESULTS: Patient characteristics, including age, sex, risk factors, adjunctive postinfarction therapy, infarct location, and baseline left ventricular volumes and ejection fraction, were similar between groups (P >.05 for all). For both groups, deceleration time decreased nonsignificantly from day 1 to day 3 and increased on day 7 (P <.001, for both groups), increasing nonsignificantly subsequently. The E/A ratio increased in the entire study group throughout the time of study (P <.001, for both groups). The pattern of changes of deceleration time was similar in both groups (P >.05 by analysis of variance), as was in subgroups determined by early reperfusion success. CONCLUSIONS: These data in a small clinical trial do not support a benefit of hyperbaric oxygen on left ventricular diastolic filling in patients with acute myocardial infarction treated with thrombolysis.
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Fibrinolíticos/uso terapéutico , Oxigenoterapia Hiperbárica , Infarto del Miocardio/fisiopatología , Estreptoquinasa/uso terapéutico , Disfunción Ventricular Izquierda/terapia , Anciano , Terapia Combinada , Angiografía Coronaria , Ecocardiografía Doppler , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/terapia , Factores de Riesgo , Terapia Trombolítica , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/etiología , Función Ventricular IzquierdaRESUMEN
OBJECTIVES: The aim of this study was to assess whether Frank-Starling mechanism has an independent effect on left ventricular (LV) performance in atrial fibrillation (AF). BACKGROUND: Ventricular performance in AF depends on variable contractility through the interval-force mechanism based on the ratio of preceding and pre-preceding RR intervals (RR(p)/RR(pp)). The impact of end-diastolic volume (EDV) variability, through the Frank-Starling mechanism, is not well understood. METHODS: We induced AF in 16 open chest dogs. RR intervals, LV pressure, LV volume, and aortic flow were collected for >400 beats during rapid AF (ventricular cycle length 292 +/- 66 ms). In six of the dogs, additional data were collected while average ventricular cycle length was prolonged from 258 +/- 34 ms to 445 +/- 80 ms by selective vagal nerve stimulation of the AV node. RESULTS: The relations of maximal LV power (LVPower) and peak LV pressure derivative (dP/dt) versus RR(p)/RR(pp) were fitted to the equation y = A * (1 - EXP (RR(p)/RR(pp)min - RR(p)/RR(pp))/C) and the residuals (RES) of these relations were analyzed. LVPower and dP/dt strongly correlated with RR(p)/RR(pp) (r(2) = 0.67 +/- 0.12 and 0.66 +/- 0.12, P < .0001 for all correlations). Importantly, RES-LVPower and RES-dP/dt showed linear correlation with EDV (r(2) = 0.20 +/- 0.14 and r(2) = 0.24 +/- 0.17, P < .01 for all correlations). In the six dogs with slowed average ventricular rate, the slope of both residual relationships (RES-LVPower vs EDV and RES- dP/dt vs EDV) decreased (P < .03 for both). CONCLUSIONS: The Frank-Starling mechanism contributes to ventricular performance in AF independently of the interval-force effects of the beat-to-beat variability in cardiac contractility. The Frank-Starling mechanism is sensitive to the average ventricular rate.
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Fibrilación Atrial/fisiopatología , Técnicas Electrofisiológicas Cardíacas , Contracción Miocárdica/fisiología , Miocardio , Función Ventricular Izquierda/fisiología , Potenciales de Acción , Animales , Fibrilación Atrial/terapia , Perros , Hemodinámica , Modelos Animales , Modelos Cardiovasculares , Función VentricularRESUMEN
Atrial fibrillation (AF) is characterized by short and irregular ventricular cycle lengths (VCL). While the beneficial effects of heart rate slowing (i.e., the prolongation of VCL) in AF are well recognized, little is known about the impact of irregularity. In 10 anesthetized dogs, R-R intervals, left ventricular (LV) pressure, and aortic flow were collected for >500 beats during fast AF and when the average VCL was prolonged to 75%, 100%, and 125% of the intrinsic sinus cycle length by selective atrioventricular (AV) nodal vagal stimulation. We used the ratio of the preceding and prepreceding R-R intervals (RR(p)/RR(pp)) as an index of cycle length irregularity and assessed its effects on the maximum LV power, the minimum of the first derivative of LV pressure, and the time constant of relaxation by using nonlinear fitting with monoexponential functions. During prolongation of VCL, there was a pronounced decrease in curvature with the formation of a plateau, indicating a lesser dependence on RR(p)/RR(pp). We conclude that prolongation of the VCL during AF reduces the sensitivity of the LV performance parameters to irregularity.
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Fibrilación Atrial/fisiopatología , Frecuencia Cardíaca , Ventrículos Cardíacos/fisiopatología , Función Ventricular , Animales , Estimulación Cardíaca Artificial , Perros , Electrocardiografía , Técnicas Electrofisiológicas Cardíacas , Hemodinámica/fisiología , Modelos Lineales , Dinámicas no Lineales , Nervio Vago/fisiología , Función Ventricular Izquierda/fisiologíaRESUMEN
BACKGROUND: Selective atrioventricular nodal (AVN) vagal stimulation (AVN-VS) has emerged as a novel strategy for ventricular rate (VR) control in atrial fibrillation (AF). Although AVN-VS preserves the physiological ventricular activation sequence, the resulting rate is slow but irregular. In contrast, AVN ablation with pacemaker implantation produces retrograde activation (starting at the apex), with regular ventricular rhythm. We tested the hypothesis that, at comparable levels of VR slowing, AVN-VS provides hemodynamic benefits similar to those of ablation with pacemaker implantation. METHODS AND RESULTS: AVN-VS was delivered to the epicardial fat pad that projects parasympathetic nerve fibers to the AVN in 12 dogs during AF. A computer-controlled algorithm adjusted AVN-VS beat by beat to achieve a mean ventricular RR interval of 75%, 100%, 125%, or 150% of spontaneous sinus cycle length. The AVN was then ablated, and the right ventricular (RV) apex was paced either irregularly (i-RVP) using the RR intervals collected during AVN-VS or regularly (r-RVP) at the corresponding mean RR. The results indicated that all 3 strategies improved hemodynamics compared with AF. However, AVN-VS resulted in significantly better responses than either r-RVP or i-RVP. i-RVP resulted in worse hemodynamic responses than r-RVP. The differences among these modes became less significant when mean VR was slowed to 150% of sinus cycle length. CONCLUSIONS: AVN-VS can produce graded slowing of the VR during AF without destroying the AVN. It was hemodynamically superior to AVN ablation with either r-RVP or i-RVP, indicating that the benefits of preserving the physiological antegrade ventricular activation sequence outweigh the detrimental effect of irregularity.