Live longer and better without prosthesis-patient mismatch

In this issue of The Journal of Heart Valve Disease, Urso and co-workers (1) analyzed the impact of prosthesispatient mismatch (PPM) on survival and quality of life following aortic valve replacement (AVR) in 163 patients aged 75 years or more. Elderly patients currently represent a large proportion of the population undergoing AVR, and this proportion is expected to grow exponentially in the near future as the population ages. In this context, it becomes appropriate to determine the exact impact of PPM in this specific population in order to adopt the most appropriate strategies with regards to this age group. Indeed, these patients have often outlived their normal life expectancy, and their main motivation for consenting to surgery may be the expectation of an improved and/or maintained quality of life, rather than a prolonged survival. In this respect, the study by Urso et al. (1) is most interesting as these authors have analyzed the impact of PPM not only on the patients’ survival but also on their quality of life. Importantly, they found that, whereas moderate PPM had no impact on mid-term mortality in this cohort of elderly patients, it was nonetheless associated with a significant reduction in the quality of life

Paradoxical low flow and/or low gradient severe aortic stenosis despite preserved left ventricular ejection fraction: implications for diagnosis and treatment

Paradoxical low flow, low gradient, severe aortic stenosis (AS) despite preserved ejection fraction is a recently described clinical entity whereby patients with severe AS on the basis of aortic valve area have a lower than expected gradient in relation to generally accepted values. This mode of presentation of severe AS is relatively frequent (up to 35% of cases) and such patients have a cluster of findings, indicating that they are at a more advanced stage of their disease and have a poorer prognosis if treated medically rather than surgically. Yet, a majority of these patients do not undergo surgery likely due to the fact that the reduced gradient is conducive to an underestimation of the severity of the disease and/or of symptoms. The purpose of this article is to review and further analyse the distinguishing characteristics of this entity and to present its implications with regards to currently accepted guidelines for AS severity

Hemodynamic and physical performance during maximal exercise in patients with an aortic bioprosthetic valve Comparison of stentless versus stented bioprostheses

AbstractOBJECTIVESThe objective of this study was to compare stentless bioprostheses with stented bioprostheses with regard to their hemodynamic behavior during exercise.BACKGROUNDStentless aortic bioprostheses have better hemodynamic performances at rest than stented bioprostheses, but very few comparisons were performed during exercise.METHODSThirty-eight patients with normally functioning stentless (n = 19) or stented (n = 19) bioprostheses were submitted to a maximal ramp upright bicycle exercise test. Valve effective orifice area and mean transvalvular pressure gradient at rest and during peak exercise were successfully measured using Doppler echocardiography in 30 of the 38 patients.RESULTSAt peak exercise, the mean gradient increased significantly less in stentless than in stented bioprostheses (+5 ± 3 vs. +12 ± 8 mm Hg; p = 0.002) despite similar increases in mean flow rates (+137 ± 58 vs. +125 ± 65 ml/s; p = 0.58); valve area also increased but with no significant difference between groups. Despite this hemodynamic difference, exercise capacity was not significantly different, but left ventricular (LV) mass and function were closer to normal in stentless bioprostheses. Overall, there was a strong inverse relation between the mean gradient during peak exercise and the indexed valve area at rest (r = 0.90).CONCLUSIONSHemodynamics during exercise are better in stentless than stented bioprostheses due to the larger resting indexed valve area of stentless bioprostheses. This is associated with beneficial effects with regard to LV mass and function. The relation found between the resting indexed valve area and the gradient during exercise can be used to project the hemodynamic behavior of these bioprostheses at the time of operation. It should thus be useful to select the optimal prosthesis given the patient’s body surface area and level of physical activity

Impact of Prosthesis-Patient Mismatch on Long-Term Survival After Aortic Valve Replacement Influence of Age, Obesity, and Left Ventricular Dysfunction

ObjectivesThis study was designed to evaluate the effect of valve prosthesis-patient mismatch (PPM) on late survival after aortic valve replacement (AVR) and to determine if this effect is modulated by patient age, body mass index (BMI), and pre-operative left ventricular (LV) function.BackgroundWe recently reported that PPM is an independent predictor of operative mortality after AVR, particularly when associated with LV dysfunction.MethodsThe indexed valve effective orifice area (EOA) was estimated in 2,576 patients having survived AVR and was used to define PPM as not clinically significant if it was >0.85 cm2/m2, as moderate if >0.65 and ≤0.85 cm2/m2, and severe if ≤0.65 cm2/m2.ResultsAfter adjustment for other risk factors, severe PPM was associated with increased late overall mortality (hazard ratio [HR]: 1.38; p = 0.03) and cardiovascular mortality (HR: 1.63; p = 0.0006) in the whole cohort. Severe PPM was also associated with increased overall mortality in patients <70 years old (HR: 1.77; p = 0.002) and in patients with a BMI <30 kg/m2 (HR: 2.1; p = 0.006), but had no impact in older patients or in obese patients. Moderate PPM was a predictor of mortality in patients with LV ejection fraction <50% (HR: 1.21; p = 0.01), but not in patients with preserved LV function.ConclusionsModerate PPM is associated with increased late mortality in patients with LV dysfunction, but with normal prognosis in those with preserved LV function. Notwithstanding the previously demonstrated deleterious effect of severe PPM on early mortality, this factor appears to increase late mortality only in patients <70 years old and/or with a BMI <30 kg/m2 or an LV ejection fraction <50%

Modulation of metoprolol pharmacokinetics and hemodynamics by diphenhydramine coadministration during exercise testing in healthy premenopausal women

Premenopausal women may be most vulnerable to acute coronary syndromes at a point in their menstrual cycle when their plasma estrogen levels are the lowest during and immediately after menstruation. Metoprolol is a first-line drug in the management of patients with acute coronary syndrome; however, when metoprolol was marketed in 1982, women were largely excluded from clinical trials. Furthermore, the over-the-counter antihistamine diphenhydramine inhibited the metabolism of the CYP2D6 substrate metoprolol in healthy, young men with pharmacokinetic and pharmacodynamic consequences. The pharmacokinetics and pharmacodynamics of metoprolol and its interaction with diphenhydramine were investigated in a randomized, double-blind, crossover, placebo-controlled manner in healthy, premenopausal extensive (EM; n = 16) and poor metabolizer (PM; n = 4) women immediately after menstruation. During the placebo phase, EMs had between 5.2- and 8.4-fold higher total clearance (CL/F) of R- and S-metoprolol compared with PMs, whereas the latter had a 35% greater area under the effect curve (AUEC) and 60% greater EC(50) value for heart rate reduction than EMs (all P < 0.05). Diphenhydramine coadmininstration caused a 2.2- to 3.2-fold decrease in CL/F of metoprolol enantiomers with a resulting 21% increase in AUEC and 29% increase in EC(50) value for heart rate reduction in EMs (all P < 0.05). This is the first study to report an in-depth elucidation of metoprolol's pharmacokinetics and hemodynamics in premenopausal EM and PM women at a point in their menstrual cycle when vulnerability for acute coronary events may be greatest. Caution is warranted when the over-the-counter antihistamine diphenhydramine is part of a chronic therapeutic regime