Natural History Of Aortic Stenosis Research Articles

Effects of SGLT2 inhibition on cardiac remodeling and heart failure development in rats with aortic stenosis

Abstract Introduction Aortic stenosis prevalence has been increasing as population ages. Currently, no medical therapies influence the natural history of aortic stenosis. Sodium glucose co-transporter 2 inhibitors (SGLT2i) have reduced heart failure hospitalization and cardiovascular mortality in heart failure patients with both reduced and preserved ejection fraction. The aim of this study was to evaluate the effects of SGLT2 inhibitor empagliflozin (EMPA) on cardiac remodeling and heart failure development in aortic stenosis rats. Methods Eighteen weeks after supra-aortic banding surgery, male Wistar rats were divided in four groups: Sham (n=15); sham + EMPA (Sham-EMPA, n=16); aortic stenosis (AS, n=27); and aortic stenosis + EMPA (AS-EMPA, n=27). Empagliflozin (10 mg/kg/day) was added to rat chow for 8 weeks. Echocardiogram was performed to evaluate cardiac structure and function. Myocardial collagen content was quantified by histology; activity of antioxidant enzymes and enzymes involved in energy metabolism was assessed by spectrophotometry. Protein expression was quantified by Western blot, and matrix metalloproteinase (MMP) activity by zymography. Statistical analysis: ANOVA and Bonferroni or Kruskal-Wallis and Dunn (p<0.05). Results AS-EMPA group had a lower frequency of anatomopathological heart failure features, a lower left ventricular (LV) dilatation (LV diastolic diameter: Sham 8.39±0.57; Sham-EMPA 8.25±0.38; AS 9.80±0.53; AS-EMPA 9.08±0.87 mm; LV systolic diameter: Sham 4.24±0.68; Sham-EMPA 4.19±0.57; AS 5.72±0.74; AS-EMPA 5.09±1.08 mm) and LV mass (Sham 0.85±0.11; Sham-EMPA 0.82±0.07; AS 2.19±0.27; AS-EMPA 1.76±0.34 g), and better diastolic function (isovolumetric relaxation time: Sham 28.6±2.28; Sham-EMPA 29.8±3.04; AS 18.9±2.59; AS-EMPA 22.9±5.02 ms) than AS. Systolic function was impaired in both AS and AS-EMPA compared to their respective controls and did not differ between AS-EMPA and AS. AS and AS-EMPA had larger myocyte diameter, higher interleukin-6 protein expression and lower catalase activity than Sham and Sham-EMPA, respectively. AS and AS-EMPA groups had lower enzyme activity from energy metabolism than their respective controls. AS presented higher lipid hydroperoxide concentration, collagen III and p65 NF-kB protein expression, and lower glutathione peroxidase activity than Sham. AS-EMPA had higher collagen I expression and inactive MMP-2 than Sham-EMPA. AS-EMPA presented higher glutathione peroxidase and intermediary active MMP-2, and lower interstitial collagen fraction (Sham 2.68±0.59; Sham-EMPA 3.16±0.33; AS 5.68±0.97; AS-EMPA 3.55±0.70 %) than AS. Conclusion Empagliflozin improves cardiac remodeling, diastolic function and myocardial oxidative stress, and reduces heart failure feature frequency and interstitial collagen fraction in aortic stenosis rats.

Abstract 11290: Sex Differences in the Progression and Long-Term Outcomes of Native Mild to Moderate Aortic Stenosis

Background: Despite evidence of sex-based divergences in the natural history of aortic stenosis (AS), there is limited data on the sex differences in the hemodynamic progression and long-term outcomes of early-stage AS. Methods: This is a retrospective longitudinal study of patients aged ≥ 60 years with mild to moderate native AS who were identified from a tertiary care referral center between 2008-2016 and followed until 2018. All patients had at minimum 2 echocardiograms. The primary outcomes of all-cause mortality and aortic valve replacement (AVR) were both assessed by time-to-event analyses with multivariable-adjusted Cox regression. The secondary outcome of AS progression was assessed by annualized changes in echocardiographic parameters in a 1:1 propensity-matched group of males and females. Results: Of 2,660 included patients followed over a median duration of 5.6 years, the mean age was 74 years and 1,128 (42%) were female. There was no difference in all-cause mortality between sexes, irrespective of age, baseline AS severity, and receipt of AVR. Relative to males, females had a lower risk of AVR (aHR=0.77, 95% CI [0.65-0.92]; p=0.004) irrespective of age, type of aortic valve and baseline severity of AS (Figure). This finding persisted on sensitivity analyses excluding patients with a history of coronary artery disease, prior coronary bypass surgery (CABG), and who underwent concomitant CABG and AVR. On 1:1 propensity-matched analysis, females had significantly slower annualized decrease in indexed aortic valve area (-0.039 vs. -0.021 cm 2 /m 2 /year, p=0.04) and slower increase in mean gradient (1.60 vs. 1.01 mmHg/year, p<0.001),and maximum transvalvular velocity (0.08 vs. 0.11 m/s/year; p=0.04). Conclusion: In patients with mild to moderate AS, females had slower hemodynamic progression of AS and lower incidence of AVR despite similar mortality between sexes. Our findings suggest the need for sex-specific evaluation and management of native AS.

Prognostic Value of Lung Ultrasound in Aortic Stenosis.

Background: Aortic stenosis (AS) is the most common primary valve lesion requiring intervention in Europe and North America. It has a prolonged subclinical period during which, as AS worsens, left ventricular adaptation becomes inadequate and impaired systolic and/or diastolic dysfunction may lead to overt heart failure (HF). The development of HF is an inflexion point in the natural history of AS. Pulmonary congestion is a cardinal feature in HF, and lung ultrasound (LUS) evaluation of B-lines has been proposed as a simple, noninvasive tool to assess pulmonary congestion. Aim: To assess the presence and the prognostic value of sonographic pulmonary congestion in patients with moderate or severe AS. Methods: 75 consecutive patients (39 women, mean age 73.85 ± 7.7 years) with moderate or severe AS were enrolled. All patients underwent comprehensive echocardiography and LUS with the 28 scanning-site assessment. Patients were followed-up for 13.4 ± 6 months to establish the prognostic value of LUS. A composite endpoint of death (of any cause), hospitalization for HF and intensification of loop diuretic therapy was considered. Results: We found a severe degree of B-lines (≥30) in 29.33% of patients. The number of B-lines correlated with the estimated pulmonary artery systolic pressure (p < 0.001, r = 0.574) and increased along with NYHA class (p < 0.05, rho = 0.383). At multivariable analysis, B-lines ≥30, and mean gradient were the independent predictors of events [B-lines: 2.79 (CI 1.03–7.54), p = 0.04; mean gradient: 1.04 (CI 1.01–1.07), p = 0.004]. Conclusion: Evaluation of B-lines is a simple, highly feasible method to detect pulmonary congestion in AS. The number of B-lines correlates with the hemodynamic changes caused by AS and with the functional status of patients. A severe degree of sonographic pulmonary congestion is associated with an increased risk of adverse events.

NATURAL HISTORY OF CONGENITAL ISOLATED MILD AORTIC VALVE AND MILD PULMONARY VALVE STENOSIS: A SINGLE CENTER FOLLOW-UP STUDY

Objective: Most of the available information on the natural history of aortic stenosis (AS) and pulmonary stenosis (PS) in children is based on studies carried out over the past 35-40 years using cardiac catheterization. This study aimed to reveal the natural history of congenital isolated mild valvular AS and PS in children using serial Doppler echocardiographic examinations. Materials and Methods: A total of 125 children, 50 with mild AS and 75 with mild PS, who underwent Doppler echocardiography were included in this study. The prognoses of mild AS and PS were compared according to age, gender, and valvular gradient at the time of initial diagnosis. Results: The mean age of patients was 26.1±37.6 months at diagnosis. The mean follow-up duration was 27.65±21.60 (1- 120) months. There was a significant decrease in the final gradient of the PS group compared to the baseline (23.58±6.97 vs. 19.88±11.21 mmHg, p=0.001). In the AS group, there was an increase in the final gradient, which was more pronounced in patients ≤1-year-old (22.42±6.12 vs. 27.74±14.12 mmHg, p=0.002). Four percent of patients in the PS group and 12% of patients in the AS group progressed to moderate to severe stenosis. All patients who progressed in the PS group were ≤1-year-old and male. Conclusion: The results showed that mild PS had a better prognosis than mild AS and that the risk of progression in AS was higher. Careful follow-up should be performed in mild PS cases ≤1-year-old, especially in boys, since progression may be detected, even if infrequently. Mild AS should also be followed closely, as the disease may show progressive characteristics in all age groups.

Implications of Coexisting Aortic Regurgitation in Patients With AorticStenosis.

Aortic regurgitation (AR) is a common comorbidity in patients with aortic stenosis (AS), but coexisting AR has often been excluded from major clinical studies on AS. The impact of coexisting AR on the natural history of AS has not been well-described. The authors compared clinical outcomes in medically managed patients with moderate-to-severe AS with or without coexisting AR. Consecutive patients (N=1,188) with index echocardiographic diagnosis of moderate-to-severe AS (aortic valve area<1.5cm2) were studied. All patients were medically managed and were divided into those with coexisting AR (at least moderate severity) and those without. Adverse composite clinical outcomes were defined as mortality or admissions for congestive cardiac failure on subsequent follow-up. The authors compared differences in clinical profile and outcomes between the groups. There were 88 patients (7.4%) with coexisting AR and AS. These patients did not differ significantly in age, but had lower body mass index (22.9 ± 3.8 vs 25.3 ± 5.1kg/m2), lower diastolic blood pressure (68.7 ± 10.7 vs 72.2 ± 12.3mmHg), larger end-diastolic volume index (68.8 ± 18.8 vs 60.4 ± 17.8mL/m2) and larger left ventricular mass index (118.6 ± 36.4 vs 108.9 ± 33.1 g/m2). The prevalence of cardiovascular risk factors did not differ significantly. Coexisting AR was associated with increased incidence of adverse outcomes (log-rank 4.20; P=0.040). On multivariable Cox regression, coexisting AR remained independently associated with adverse outcomes (HR: 1.36; 95%CI: 1.02-1.82) after adjusting for age, AS severity, left ventricular ejection fraction, and year of study. In patients with AS, coexisting AR was associated with changes in echocardiographic profile and adverse outcomes.

Co-existing aortic regurgitation associated with adverse clinical outcomes in patients with moderate to severe aortic stenosis

Abstract Background Aortic regurgitation (AR) is a common comorbidity in patients with aortic stenosis (AS), but co-existing AR has often been an exclusion criterion from major clinical trials. The impact of co-existing AR on the natural history of AS has not been well-described. Purpose We compared clinical outcomes in patients with moderate to severe AS with or without co-existing AR. Methods Consecutive patients (n=1188) with index echocardiographic diagnosis of moderate to severe AS (AVA &amp;lt;1.5cm2) were studied. They were divided into those with co-existing AR (at least moderate severity) and those without. Adverse composite clinical outcomes were defined as either mortality or admissions for congestive cardiac failure on subsequent follow-up for at least five years. Appropriate univariate and multivariable analyses were employed to compare the two groups. Results There were 88 patients (7.4%) with co-existing AR and AS. These patients did not differ significantly in age, but had lower body mass index (22.9±3.8 vs 25.3±5.1 kg/m2). They also had lower diastolic blood pressure (68.7±10.7 vs 72.2±12.3 mmHg), larger end-diastolic volume index (68.8±18.8 vs 60.4±17.8 ml/m2) and left ventricular mass index (118.6±36.4 vs 108.9±33.1 g/m2). The prevalence of cardiovascular risk factors did not differ significantly between the groups. Co-existing AR was associated with adverse outcomes (log-rank 4.20, p=0.040). On multivariable Cox-regression, co-existing AR remained independently associated with adverse outcomes (hazard ratio 1.51, 95% CI 1.13–2.02) after adjusting for age, AS severity and left ventricular ejection fraction. Conclusion In patients with AS, co-existing AR was associated with a distinct echocardiographic profile and adverse outcomes. Funding Acknowledgement Type of funding source: None

Ventricular stroke work and vascular impedance refine the characterization of patients with aortic stenosis.

Aortic stenosis (AS) management is classically guided by symptoms and valvular metrics. However, the natural history of AS is dictated by coupling of the left ventricle, aortic valve, and vascular system. We investigated whether metrics of ventricular and vascular state add to the appreciation of AS state above valve gradient alone. Seventy patients with severe symptomatic AS were prospectively followed from baseline to 30 days after transcatheter aortic valve replacement (TAVR). Quality of life (QOL) was assessed using the Kansas City Cardiomyopathy Questionnaire. Left ventricular stroke work (SWLV) and vascular impedance spectrums were calculated noninvasively using in-house models based on central blood pressure waveforms, along with hemodynamic parameters from echocardiograms. Patients with higher preprocedural SWLV and lower vascular impedance were more likely to experience improved QOL after TAVR. Patients fell into two categories: those who did and those who did not exhibit increase in blood pressure after TAVR. In patients who developed hypertension (19%), vascular impedance increased and SWLV remained unchanged (impedance at zeroth harmonic: Z 0, from 3964.4 to 4851.8 dyne·s/cm3, P = 0.039; characteristic impedance: Z c, from 376.2 to 603.2 dyne·s/cm3, P = 0.033). SWLV dropped only in patients who did not develop new hypertension after TAVR (from 1.58 to 1.26 J; P < 0.001). Reduction in valvular pressure gradient after TAVR did not predict change in SWLV (r = 0.213; P = 0.129). Reduction of SWLV after TAVR may be an important metric in management of AS, rather than relying solely on the elimination of transvalvular pressure gradients.

Relation of Clinical Presentation of Aortic Stenosis and Survival Following Transcatheter Aortic Valve Implantation

Although the natural history of aortic stenosis (AS) depends on the severity of symptoms, the prognostic significance of AS clinical progression in patients who underwent aortic valve replacement is less clear. Here, we studied the correlation between the severity of AS presenting symptoms and survival after transcatheter aortic valve implantation (TAVI). We evaluated long-term survival of a consecutive cohort of severe AS patients (n = 862, mean Society of Thoracic Surgeons score 4.16 ± 2.9) who underwent transfemoral TAVI from 2009 to 2016. Patients were classified as having severe symptoms (i.e., angina, syncope, or heart failure, n = 424) or mild symptoms (i.e., dizziness, fatigue, effort dyspnea, chest discomfort, n = 438). No differences in device success nor in-hospital complications were found between groups. During a median follow-up of 2.84 (1.9 to 4.5) years, survival at 1, 3, and 5 years in the entire cohort, was 89% ± 1.1%, 75% ± 1.6%, and 59% ± 2.1%, respectively. Severe symptoms were associated with higher mortality (hazard ratio 1.54, 95% confidence intervals 1.230 to 1.939, p <0.001). The 1-, 3-, and 5-year survival was 94% ± 1.9%, 81% ± 3.3%, and 71% ± 4.3% in patients with angina, 92% ± 3.3%, 75% ± 5.6%, and 56% ± 8.2% in patients with syncope and 77% ± 3%, 54% ± 3.7%, and 41% ± 4.1% in patients with heart failure, respectively, (p <0.001). Heart failure symptoms emerged as independent predictor of mortality (hazard ratio 1.66, 1.28 to 2.17, p <0.001), regardless of left ventricular ejection fraction. The severity of AS symptoms affects survival after TAVI and overt heart failure independently predicts early mortality. Early intervention after diagnosis of severe AS is crucial to reduce the unfavorable effects of clinical progression on survival after TAVI.

THE ROLE OF VENTRICULAR STROKE WORK AND VASCULAR IMPEDANCE IN DEFINING AORTIC STENOSIS

Aortic stenosis (AS) management remains guided by symptoms and valvular metrics. Yet the natural history of AS is dictated by the coupling of the left ventricle (LV) proximally, the valve itself, and vascular system distally. our objectives were to investigate the role of LV stroke work (SWLV) and

Aortic Valve Area Index

> It is generally believed that, (aortic valve) organic disease being once established … is progressive … must end in death, either by rupture of the valves, organic disease of the remaining portion of the heart, or obstruction to the current of blood. … but … this disorganizing process may be occasionally of singular slowness, so that the patient may live for many years in the enjoyment of good, or at least tolerable health, or that the diseased action is really arrested and the lesion becomes stationary. Thus, did William Stokes categorize the uncertain natural history of aortic stenosis (AS) more than a century and half ago.1 Since his elegant description, AS has remained an enigmatic problem, particularly in the absence of symptoms. On one hand, the presence of typical symptoms and a peak transaortic velocity of >4 m/s and a valve area of 50 years ago.2 In the absence of symptoms, however, the relation between aortic valve area (AVA) and prognosis becomes much less certain; every cardiologist struggles with the question of when (if at all) to intervene upon such patients. Will their fate “end in death” as Stokes lamented or will they be among the fortunate who “live for many years… (as) the lesion becomes stationary.” See …

Left Ventricular Hypertrophy in Asymptomatic Nonsevere Aortic Stenosis

Increased biomechanical stress on cardiomyocytes because of outflow obstruction secondary to aortic stenosis (AS) is thought to induce reexpression of the fetal gene program, which modifies myocyte efficiency, sarcomere composition, and regulation of extracellular matrix, as well as various nuclear signal transduction pathways resulting in autocrine production and secretion of cytokines, neurohormones and growth factors that ultimately promote ventricular hypertrophy.1,2 See Article by Gerdts et al The traditional view of adaptative concentric left ventricular hypertrophy (LVH) because of parallel replication of new sarcomeres is that wall thickness increases to normalize LV systolic wall stress and preserve systolic performance. This view, accepted for the past 40 years3 and perhaps counterintuitively expected to mitigate the effects of LV pressure overload on cardiovascular morbidity and mortality, has begun to be challenged by new clinical data, suggesting that moderate or severe LVH may be associated with adverse outcomes in AS4,5 and that inappropriately increased LV mass, found in 17% of patients with mild to moderate AS6 and in 67% of patients with asymptomatic severe AS, was associated with a 4.5-fold increased risk of cardiovascular events.7 Conversely, the absence of hypertrophy in one third of the patients with severe AS seems to have no adverse effects on systolic function or survival.8,9 Experimental studies in genetically modified animal models are consistent with clinical observations.10 In addition, no association was found between AS severity and the magnitude or pattern of LVH using cardiac magnetic resonance.11 Thus, it seems that the presence, severity, and the geometric pattern of LVH in AS vary widely, are …

Fetal intervention for critical aortic stenosis: advances, research and postnatal follow-up.

Fetal aortic valvuloplasty is intended to alter the natural history of aortic stenosis evolving to hypoplastic left heart syndrome. The most recently reported data and advances on this procedure were reviewed. The highlights of the latest experience are the advances in further understanding of the prenatal and postnatal natural history of this disease, and the way in which fetal aortic valvuloplasty impacts on it, the identification of new predictors of biventricular outcome, and the report of postnatal survival of intervened patients. Recently reported short-term and middle-term results are encouraging. Experimental research on procedural aspects is ongoing, with no definite results. Multicenter studies are also ongoing. In recent years, there have been advances in the understanding of the prenatal and postnatal process of aortic stenosis evolving to hypoplastic left heart syndrome and the effects of fetal aortic valvuloplasty, as well as the need of adequate postnatal therapeutic strategies for these patients. Procedural aspects are being studied with animal models, but still need far more experience before human application. Long-term results are still to be discovered, and multicenter studies may provide a new perspective. Continuing research is mandatory so that ultimately fetal heart intervention finds its place among the therapeutic resources for congenital heart disease.

Accurate Assessment of Aortic Stenosis

Aortic valve (AV) stenosis is one of the most common valvular diseases and is the third most common cardiovascular disease in developed countries. It occurs in ≈2.8% of patients ≥75 years of age and can occur because of degenerative calcification and congenital valvular defects such as bicuspid AVs or rheumatic disease.1–3 Calcific aortic stenosis (AS) is associated with increased leaflet stiffness and a narrowed AV orifice, resulting in increased pressure gradients across the valve. The presence of a bicuspid AV significantly increases the risk of AS.4 The natural history of AS is a prolonged asymptomatic period, with progressive reduction of the AV orifice area due to sclerosis initially, culminating in calcific AS. This is accompanied by a corresponding increase in the transaortic pressure gradient (Δ P ) and myocardial pressure overload. Through the preload reserve, the left ventricle (LV) compensates for the increased workload until the sarcomeres stretch to their maximum diastolic length. Once the preload reserve is exhausted, increases in afterload are accompanied by a reduction in stroke volume (SV), resulting in afterload mismatch. Ultimately, this causes LV hypertrophy, associated with an enlargement of cardiac myocytes and increased LV wall thickness.5 Initial diagnosis of AS typically occurs during routine physical examination with the presence of a heart murmur, click, or other abnormal sounds, but undiagnosed patients may experience the onset of severe symptoms such as angina, syncope, and heart failure. Without intervention, patient mortality typically occurs within 5 years of the onset of symptoms.6–11 Multiple studies and reviews have focused on the clinical aspects of this disease, including disease progression, markers of disease severity, treatment guidelines, and outcomes.1–3,6,12–16 Very few reviews have focused on the hemodynamic principles underlying AS and on comparing data obtained across different …

Symptoms in Patients With Severe Aortic Stenosis and Preserved Left Ventricular Ejection Fraction: Is It All About Diastole?

Although it has been ≈50 years since Ross and Braunwald1 reported the malignant natural history of aortic stenosis (AS) after the onset of angina, syncope, or heart failure, the pathophysiologic underpinnings of these classic symptoms remain incompletely delineated. We appreciate that angina may occur in the absence of epicardial coronary disease with both increased demand and impaired supply, contributing to imbalance of the supply–demand relationship. Exertional syncope reflecting the inability to maintain cerebral perfusion is attributed to an inability to increase cardiac output in combination with, at times, paradoxically reduced systemic vascular resistance. Although we attribute the low-output symptoms of heart failure to the same inability to increase cardiac output, we still have an incomplete understanding of the changes that restrict stroke volume augmentation. Similarly, although the dyspnea of heart failure is typically linked to elevated pulmonary capillary pressures, which of the multiple pathways leading to elevated pulmonary pressures is/are operative in the symptomatic patient with AS? Although afterload mismatch and attendant left ventricular (LV) systolic dysfunction provide a substrate for symptoms in some patients, understanding the basis for symptoms in patients with preserved LV ejection fraction (EF) is particularly challenging because measures of AS severity alone predict the onset of but correlate imperfectly with the presence of symptoms.2 Article see p 142 In this issue of Circulation: Cardiovascular Imaging , Dahl et al3 provide hypothesis-generating data that argue an important role for LV remodeling and diastolic dysfunction in the pathogenesis of symptoms in patients AS and preserved (≥50%) LVEF. They compared echocardiographic parameters in 139 asymptomatic patients assessed in an outpatient clinic and 99 symptomatic patients referred for surgical intervention. Although the symptomatic patients were surprisingly younger, had less atrial fibrillation, hypertension, and chronic lung disease than did the asymptomatic cohort, higher LV mass index and …

Hypertension in aortic stenosis: More questions than answers

Although hypertension and aortic stenosis are the most common cardiovascular diseases, the impact of hypertension on the natural history of aortic stenosis, the structure and function of the left ventricle, the assessment of valve defect severity and its progression are not fully understood. Hypertension not only can modify the exploratory findings of aortic stenosis, but may also interfere with the assessment of severity, and even have an impact on patients outcome. In the absence of specific cohort studies, the nature of the association between aortic stenosis and high blood pressure is not clear and the published results are often contradictory. Unknown is the true frequency of both conditions, the rules of diagnosis and the treatment itself.

Progression of aortic stenosis in elderly patients over long-term follow up

BackgroundThe natural history of aortic stenosis (AS) in elderly patients remains poorly defined. In an elderly cohort over long-term follow-up, we assessed: 1) rates and predictors of hemodynamic progression and 2) composite aortic valve replacement (AVR) or death endpoint. MethodsConsecutive Department of Veterans' Affairs patients with AS (>60years) were prospectively enrolled between 1988 and 1994 (n=239) and followed until 2008. Patients with ≥2 trans-thoracic echocardiograms >6months apart were included in the progression analysis (n=147). Baseline demographics, comorbidities and echocardiography parameters were recorded. Follow-up was censored at AVR/death. ResultsThe age of patients was 73±6 years; 82% were male. Baseline AS severity was mild (67%), moderate (23%) and severe (10%). Follow-up was 6.5±4 years (range: 1–17years). Annualized mean aortic valve gradient progression rates were: mild AS 4±4mmHg/year; moderate AS 6±5mmHg/year and severe AS 10±8mmHg/year (p<0.001). Five-year event-free survival was 66±5%, 23±7% and 20±10% for mild, moderate and severe AS respectively. Progression to severe AS occurred in 35% and 74% of patients with mild and moderate AS respectively. Independent predictors of rapid progression were: baseline AS severity (per grade) (OR 2.6, p=0.001), aortic valve calcification (per grade) (OR 2.1, p=0.01), severe renal impairment (OR 4.0, p=0.04) and anemia (OR 2.3, p=0.05). ConclusionsIn elderly patients, hemodynamic progression of AS is predicted by AS severity, renal function, aortic valve calcification and history of anemia. These factors identify patients at high risk of rapid hemodynamic progression, for whom more frequent clinical and echocardiographic surveillance is advisable.

A new standard of care for inoperable, severe aortic stenosis: implications of the PARTNER trial

Calcific aortic stenosis (AS) is the most common form of valvular heart disease requiring intervention in the developed world. Although indolent early in its course, the disease becomes extremely malignant following the development of symptoms with an average survival of only 2–3 years and a high rate of sudden death. Until recently, surgical aortic valve replacement (AVR) had been the only therapy demonstrated to alter the natural history of AS and improve mortality. Standard medical therapy, including balloon aortic valvuloplasty, can lead to a short-term improvement in symptoms, but does not improve survival. The Placement of Aortic Transcatheter Valves (PARTNER) trial compared transcatheter aortic valve replacement (TAVR) with standard therapy in patients with symptomatic, severe AS who were inoperable (cohort B) or high-risk (cohort A) candidates for AVR. In cohort B of the trial, TAVR with the Edwards SAPIEN valve significantly reduced the primary end point of overall mortality at 1 year among patie...

Myocardial remodeling with aortic stenosis and after aortic valve replacement: Mechanisms and future prognostic implications

Aortic valve stenosis is a common cause of left ventricular pressure overload, a pathologic process that elicits myocyte hypertrophy and alterations in extracellular matrix composition, both of which contribute to increases in left ventricular stiffness. However, clinical and animal studies suggest that increased myocardial extracellular matrix fibrillar collagen content occurs later in the time course of left ventricular pressure overload at a time coincident with severe abnormalities in diastolic function followed by the development of symptomatic heart failure. Aortic valve replacement remains the most effective treatment for elimination of chronic pressure overload secondary to aortic stenosis but has traditionally been recommended only after the onset of clinical symptoms. Long-term follow-up of patients with symptomatic aortic stenosis after aortic valve replacement suggests that valve replacement may not result in complete reversal of the maladaptive changes that occur within the myocardial extracellular matrix secondary to the pressure overload state. To the contrary, residual left ventricular extracellular matrix abnormalities such as these are likely responsible for persistent abnormalities in diastolic function and increased morbidity and mortality after aortic valve replacement. Defining the mechanisms and pathways responsible for regulating the myocardial extracellular matrix during the natural history of aortic stenosis may provide a means by which to detect crucial structural milestones and thereby permit more precise identification of the development of maladaptive left ventricular remodeling.

Natural history of aortic stenosis

Natural history of aortic stenosis

Predicting outcome in asymptomatic aortic stenosis: should we measure the severity of obstruction or its physiological consequences?

This editorial refers to ‘Left ventricular systolic and diastolic function assessed by tissue Doppler imaging and outcome in asymptomatic aortic stenosis’, by R.A.H. Stewart et al. doi:10.1093/eurheartj/ehq159 ‘Information is not knowledge’.Albert Einstein In patients with severe aortic stenosis, it is well recognized that when symptoms develop, death will ensue unless the obstruction is relieved. Development of cardiac symptoms of angina, syncope, or heart failure indicate that a critical severity of obstruction has occurred and mark a change in the natural history of aortic stenosis. However, symptoms may be subtle, especially in the elderly patient who may have co-morbidities, including arthritis, lung disease, neurological disease, and frailty, that limit exercise capacity. Even if symptoms are realized, these may not be reported by the patient. Moreover, even in the truly asymptomatic patient, it is recognized that aortic stenosis is associated with a small risk of sudden death, which has been estimated at 1% per year.1 Because of difficulties in determining exactly when the symptomatic stage of aortic stenosis has developed, and because of the risk of sudden death, many efforts have been made to predict outcomes in aortic stenosis accurately. Multiple investigators have tried to characterize the clinical, electrocardiographic, haemodynamic, imaging, and biomarker features which identify the patient at risk of adverse outcome. Echocardiography has become the mainstay of diagnostic assessment in patients with aortic stenosis. Initial efforts to predict events in aortic stenosis have focused on quantifying the severity of obstruction. More recently, the physiological consequences of the obstruction, namely the effects on left ventricular (LV) mass and systolic and diastolic function, have gained attention ( Figure 1 ). The recent, carefully conducted, multicentre study by Stewart et al. 2 was intended to combine these interests and to explore the role of tissue Doppler measures of LV systolic and diastolic function …