Progression Of Aortic Stenosis In Patients Research Articles

The impact of resting heart rate on adverse outcomes and haemodynamic progression of aortic stenosis

Abstract Introduction A high resting heart rate (RHR) is an established risk factor for cardiovascular disease, adverse cardiac events, accelerated calcification in coronary artery disease and carotid stenosis, and increased aortic valve calcification in patients with and without a confirmed diagnosis of aortic stenosis (AS). Aortic valve calcification is the most common precursor to AS and is associated with significantly faster disease progression. There are few studies exploring the effects of RHR on the progression of AS, the development of severe stenosis, and the risk of complications and death. Purpose We hypothesised that an elevated RHR would be associated with poorer outcomes and more rapid haemodynamic disease progression in patients with AS and tested this in a large cohort of patients without severe disease. Methods Using the National Echocardiography Database of Australia (NEDA) we undertook a retrospective observational study on patients without severe AS, a bicuspid aortic valve or prior aortic valve replacement. The association between baseline RHR and time to the composite primary endpoint of severe AS, aortic valve replacement or cardiovascular death was tested using Cox proportional hazards regression. In addition, the relationship between baseline RHR and the components of this composite was investigated. Subsequently, the relationship between annualised AS progression rate, defined as change in standard indices of AS severity (maximal jet velocity [Vmax], mean pressure gradient [MPG], and aortic valve area [AVA]), and RHR were analysed using general linear models. Results The initial study cohort comprised 55 585 individuals: 54% male, mean age 63 years and median baseline RHR 70 bpm. The composite primary endpoint, reached by 7 434 patients, was independently associated with RHR (hazard ratio [per 10bpm increase], 1.04; 95% CI, 1.02-1.05; p < 0.001). RHR was also independently associated with time to developing severe AS (hazard ratio [per 10bpm increase], 1.06; 95% CI, 1.01-1.12; p = 0.017) and cardiovascular death (hazard ratio [per 10bpm increase], 1.04; 95% CI, 1.02-1.06; p < 0.001). The event rate was significantly higher in patients with a RHR of at least 70 bpm (the median RHR) compared to those with an RHR less than 70 bpm. In addition, RHR was independently associated with rate of change of each individual measurement index of AS severity including Vmax (β = 0.65 cm/s/year [per 10 bpm increase]; p < 0.001), MPG (β = 0.05 mmHg/ year [per 10 bpm increase]; p<0.001), and AVA (β = -0.01 cm2/year [per 10 bpm increase]; p < 0.001). Conclusions RHR is independently associated with adverse clinical outcomes and haemodynamic progression of AS in patients without severe disease. Future randomised controlled trials should investigate the effect of lowering RHR on clinical endpoints and progression of AS.

Chronic kidney disease is a key risk factor for aortic stenosis progression.

Rapid progression of aortic stenosis (AS) has been observed in patients undergoing dialysis, but existing cross-sectional evidence is contradictory in non-dialysis-dependent chronic kidney disease (CKD). The present study sought to evaluate whether CKD is associated with the progression of AS over time in a large cohort of patients with AS. We retrospectively studied all consecutive patients diagnosed with AS [peak aortic jet velocity (Vmax) ≥2.5m/s] and left ventricular ejection fraction ≥50% in the echocardiography laboratories of two tertiary centers between 2000 and 2018. The estimated glomerular filtration rate (eGFR) (mL/min/1.73m2) was calculated from serum creatinine values. Patients were divided into five CKD stages according to the baseline eGFR. Annual rates of change in the aortic valve area (AVA) were determined by a linear mixed-effects model. Among the 647 patients included, 261 (40%) had CKD. After a median follow-up of 2.9 (interquartile range 1.8-4.8) years, the mean overall rate of change in AVA was -0.077 (95% confidence interval -0.082; -0.073) cm2/year. There was an inverse relationship between the progression rate and kidney function. The more severe the CKD stage, the greater the AVA narrowing (P<.001). By multivariable linear regression analysis, the eGFR was also negatively associated (P<.001) with AS progression. An eGFR strata below 45mL/min/1.73m2 was associated with higher odds of rapid progression of AS than normal kidney function. During the clinical follow-up, event-free survival (patients free of aortic valve replacement or death) decreased as CKD progressed. Rapid progression of AS in patients with kidney dysfunction was associated with worse outcomes. Patients with CKD exhibit more rapid progression of AS over time and require close monitoring. The link between kidney dysfunction and rapid progression of AS is still unknown and requires further research.

Abstract 9260: Rate of Progression of Aortic Stenosis in Patients With Cirrhosis

Introduction: There is currently no published data studying the effect that cirrhosis may have on the rate of progression of aortic stenosis (AS). We hypothesize that AS may have accelerated progression in patients with cirrhosis compared with the general population due to high stroke volumes, hyperdynamic left ventricular function, and a pro-inflammatory state. The aim of this study is to determine the rate of progression of AS in patients with cirrhosis, elucidate risk factors, and assess progression based on the severity of cirrhosis as determined by Model for End Stage Liver Disease (MELD-Na) scores. Methods: This single center retrospective study included 48 patients with the diagnosis of cirrhosis and at least mild AS confirmed by two or more transthoracic echocardiograms (TTEs) taken ≥ 6 months apart. Historical data describing rates of AS progression in non-cirrhotic patients were used for comparison. Results: There was not a significant difference in the rate of AS progression between patients with cirrhosis and those without (table). Using univariate regression analysis, the yearly rate of aortic valve area (AVA) decline was positively correlated with the diagnosis of hyperlipidemia (HLD) (r=.228, P=0.047, B=0.116), initial AVA (r=0.504, P&lt;0.001, B=0.224), initial left ventricular outflow track to aortic valve velocity time integral ratio (LVOT:AV VTI) (r=0.519, P&lt;0.001, B=0.75) and initial left-ventricular stroke volume index (LV-SVI) (r=0.385, P=0.0070, B=0.0070). The yearly decrease of the LVOT:AV peak velocity ratio was inversely correlated with beta-blocker use (r=0.313, P=0.030, B=-0.047). There was not a significant relationship between MELD-Na scores and the rate of AS progression. Conclusion: Patients with cirrhosis can expect a similar rate of AS progression compared with those without cirrhosis. A higher initial LV-SVI and a history of HLD were both associated with faster AS progression in our study cohort.

Determinants of Aortic Stenosis Progression in Bicuspid and Tricuspid Aortic Valves.

Bicuspid aortic valve (BAV) is associated with a faster progression of aortic stenosis (AS). Whether the determinants of AS progression are the same or different in patients with BAV vs tricuspid aortic valve (TAV) is unknown. The aim of this study was to identify the factors associated with the progression of AS in patients with BAV vs patients with TAV. Patients with AS were prospectively recruited in the Metabolic Determinants of the Progression of Aortic Stenosis (PROGRESSA) study (ClinicalTrials.gov Identifier: NCT01679431). The haemodynamic progression rate of AS was assessed by the annualized progression rate of peak aortic jet velocity (Vpeak). Univariable and multivariable linear regression analyses were used to identify the factors associated with a faster progression of AS in patients with BAV vs patients with TAV. There were 79 patients with BAV and 208 patients with TAV. The baseline severity of AS was similar between the 2 groups of patients as well as the annualized progression rate of AS. In patients with BAV, obesity (β= 0.25, P= 0.04), diabetes (β= 0.26, P= 0.02), and BAV with right-noncoronary cusp fusion (β= 0.29, P= 0.01) were found to be independently associated with a faster progression of AS, whereas in patients with TAV, AS baseline severity (baseline Vpeak, β= 0.14, P= 0.04) and chronic kidney disease (β= 0.16, P= 0.02) were significantly associated with AS progression. Factors associated with progression rate of AS are different in BAV and TAV. The main factors associated with a faster progression of AS appear to be obesity, diabetes, right-noncoronary cusp fusion in patients with BAV vs chronic kidney disease in patients with TAV.

On the severity of aortic stenosis in ascending aortic aneurysm: A computational tool to examine ventricular-arterial interaction and aortic wall stress

An ascending thoracic aortic aneurysm (ATAA) is a life-threatening cardiovascular consequence of vessel dilatation that portends adverse events and death. From a clinical perspective, ATAA should not be treated as an isolated disease, and surgery is often carried out in the presence of AS, aortic insufficiency or a calcified valve leaflet. Aortic stenosis (AS) is common in ATAAs and leads to both vessel rigidity and left ventricular (LV) impairment. In this study, lumped-parameter modeling and computational analysis were used to assess the change in the wall shear stress (WSS) and intramural wall stress of patient-specific ATAA models with different degrees of AS (i.e., mild to severe). The ATAAs of four patients were reconstructed from imaging data and AS was simulated virtually using the lumped-based CircAdapt tool using clinical and echocardiographic data. Results show that LV work derived from pressure-volume loops increased with the severity of AS. Post-stenotic hemodynamic and structural variables markedly increased with AS severity, with WSS showing a 10-fold increase for the most severe AS model as compared to the baseline model with a well-functioning aortic valve. Most importantly, the increase in WSS and aortic wall stress was associated with pronounced values of valvulo-arterial impedance as an indicator of LV dysfunction. This study provides novel insights into progression of AS in patients with ATAAs at high risk of adverse events, and the potential value of valvulo-arterial impedance to predict changes in hemodynamic and structural parameters with the severity of AS.

Aortic stenosis in patients with kidney failure: Is there an advantage for a PD-first policy?

Aortic stenosis (AS) is the most common valvular disease. It is twice as prevalent in patients with kidney failure as compared to the general population. In addition, AS progresses at a faster rate and is associated with a higher risk of death and poorer quality of life in patients on dialysis. Chronic kidney disease-mineral and bone disorder (CKD-MBD), inflammation, and hemodynamic disturbances contribute to the pathophysiology and progression of AS. Whether the type of dialysis modality, that is, hemodialysis (HD) versus peritoneal dialysis (PD), has a differential impact on the development and progression of AS in patients with kidney failure remains debated. Recent data indicate that the prevalence of valvular calcifications might be lower and the development of AS delayed in PD patients, as compared to those treated with HD. This could be accounted for by several mechanisms including reduced valvular shear stress, better preservation of residual kidney function (with better removal of protein-bound uremic toxins and CKD-MBD profile), and lower levels of systemic inflammation. Given the high morbidity and mortality rates related to interventional procedures in the population with kidney failure, surgical and transcatheter aortic valve replacement should be considered in selected patients with severe AS. Strategies slowing down the progression of aortic valve remodeling should remain the cornerstone in the management of individuals with kidney failure and mild to moderate AS. This review explores the potential benefits of PD in patients with kidney failure and AS and provides some clues to help clinicians in the decision-making process when options for kidney replacement therapy are considered in patients with AS.

P1368 Effect of angiotensin receptor blocker in patients with moderate or severe aortic stenosis: a randomized controlled trial

Abstract Funding Acknowledgements This study was supported by grants from Boryung Pharmacy Research Fund. Background/Introduction: Pathophysiology of aortic stenosis (AS) and several previous studies suggested the potential role of angiotensin receptor blocker (ARB) in patients with AS. Purpose We aimed to investigate the effects of Fimasartan, an ARB, on exercise capacity and progression of AS in patients with moderate to severe AS. Methods We conducted a prospective, randomized, double-blind, placebo-controlled trial in 32 normotensive or controlled-hypertensive patients with moderate or severe AS. Study participants were randomized to Fimasartan 30 mg to 60 mg daily (n = 14) or placebo (n = 18) for 1 year, and underwent cardiopulmonary exercise test, 6-minute walk test, and echocardiography at 0, 6, and 12 months, with follow-up data available in 29 subjects. Results Significant reductions in blood pressures were observed in the Fimasartan group but not in the placebo group. Two of the 14 patients in the Fimasartan group withdrew the study due to mild symptoms probably related with the decreased blood pressure, and one patient decline the study protocol. After the 12-month treatment, the peak oxygen consumption (VO2; the primary outcome) in the Fimasartan group was significantly decreased (from 28.3 ± 5.9 to 25.4 ± 3.8 mL/min/kg, P = 0.021) but not in the placebo group (P for interaction = 0.046) (Figure 1A). The severity of AS showed a gradual progression in both groups, without inter-group differences (mean transaortic pressure; Fimasartan group, +4.0 ± 3.8 mmHg/year; placebo group, +5.3 ± 6.2 mmHg/year; P for interaction = 0.429) (Figure 1B). Parameters of left ventricular systolic and diastolic function did not change in both groups. Conclusions The use of ARB impaired exercise capacity in patients with moderate or severe AS, and did not prevent the progression of AS. However, due to the small number of participants, further studies are required to confirm these findings. Abstract P1368 Figure.

Intraleaflet haemorrhage as a mechanism of rapid progression of stenosis in bicuspid aortic valve

BackgroundThe mechanisms are unknown why aortic stenosis (AS) progresses faster in patients with bicuspid aortic valve (BAV) than those with tricuspid aortic valve (TAV). The objective of this study is to examine whether neoangiogenesis, haemorrhage in the aortic valve leaflet (intraleaflet haemorrhage) and macrophage infiltration are involved in the mechanisms of rapid progression of AS with BAV. MethodsWe retrospectively examined specimens of aortic valve leaflets obtained from patients who had undergone aortic valve replacement for AS (AS with BAV: n=22, AS with TAV: n=86). The stenotic valve leaflets were examined by immunohistochemistry to detect vascular endothelial cells, red blood cell remnant and macrophage. We assessed the progression of AS by annualized changes in the aortic valve area (ΔAVA: cm2/year) which was evaluated by serial echocardiography with the continuity equation. ResultsNeoangiogenesis, intraleaflet haemorrhage and macrophage infiltration were frequently observed in leaflets obtained from AS patients with BAV (neoangiogenesis: 82%, intraleaflet haemorrhage: 91%, macrophage infiltration 91%). These pathological changes were more severe in AS with BAV than TAV, and they were positively correlated with progression of AS in patients with BAV. Multivariated analysis revealed that bicuspid anatomy was the only factor that predicted neoangiogenesis, intraleaflet haemorrhage and macrophage infiltration when patients with BAV and those with TAV were combined. ConclusionsNeoangiogenesis, intraleaflet haemorrhage and macrophage infiltration are more severe in leaflets from AS with BAV than TAV and associated with rapid progression of AS with BAV. This pathological process may account for rapid progression of AS with BAV.

Effect of Lipid Lowering With Rosuvastatin on Progression of Aortic Stenosis

Aortic stenosis (AS) is an active process with similarities to atherosclerosis. The objective of this study was to assess the effect of cholesterol lowering with rosuvastatin on the progression of AS. This was a randomized, double-blind, placebo-controlled trial in asymptomatic patients with mild to moderate AS and no clinical indications for cholesterol lowering. The patients were randomized to receive either placebo or rosuvastatin 40 mg daily. A total of 269 patients were randomized: 134 patients to rosuvastatin 40 mg daily and 135 patients to placebo. Annual echocardiograms were performed to assess AS progression, which was the primary outcome; the median follow-up was 3.5 years. The peak AS gradient increased in patients receiving rosuvastatin from a baseline of 40.8+/-11.1 to 57.8+/-22.7 mm Hg at the end of follow-up and in patients with placebo from 41.6+/-10.9 mm Hg at baseline to 54.8+/-19.8 mm Hg at the end of follow-up. The annualized increase in the peak AS gradient was 6.3+/-6.9 mm Hg in the rosuvastatin group and 6.1+/-8.2 mm Hg in the placebo group (P=0.83). Treatment with rosuvastatin was not associated with a reduction in AS progression in any of the predefined subgroups. Cholesterol lowering with rosuvastatin 40 mg did not reduce the progression of AS in patients with mild to moderate AS; thus, statins should not be used for the sole purpose of reducing the progression of AS. Clinical Trial Registration Information- URL: http://www.controlled-trials.com/. ISRCTN 32424163.