ResearchPad - valvular-heart-disease https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Impact of myocardial fibrosis on left ventricular remodelling, recovery, and outcome after transcatheter aortic valve implantation in different haemodynamic subtypes of severe aortic stenosis]]> https://www.researchpad.co/article/elastic_article_10049 Myocardial fibrosis (MF) might represent a key player in pathophysiology of heart failure in aortic stenosis (AS). We aimed to assess its impact on left ventricular (LV) remodelling, recovery, and mortality after transcatheter aortic valve implantation (TAVI) in different AS subtypes.Methods and results One hundred patients with severe AS were prospectively characterized clinically and echocardiographically at baseline (BL), 6 months, 1 year, and 2 years following TAVI. Left ventricular biopsies were harvested after valve deployment. Myocardial fibrosis was assessed after Masson’s trichrome staining, and fibrotic area was calculated as percentage of total tissue area. Patients were stratified according to MF above (MF+) or below (MF−) median percentage MF (≥11% or <11%). Myocardial fibrosis burden differed significantly between AS subtypes, with highest levels in low ejection fraction (EF), low-gradient AS and lowest levels in normal EF, high-gradient AS (29.5 ± 26.4% vs. 13.5 ± 16.1%, P = 0.003). In the entire cohort, MF+ was significantly associated with poorer LV function, higher extent of pathological LV remodelling, and more pronounced clinical heart failure at BL. After TAVI, MF+ was associated with a delay in normalization of LV geometry and function but not per se with absence of reverse remodelling and clinical improvement. However, 22 patients died during follow-up (mean, 11 months), and 14 deaths were classified as cardiovascular (CV) (n = 9 arrhythmia-associated). Importantly, 13 of 14 CV deaths occurred in MF+ patients (CV mortality 26.5% in MF+ vs. 2% in MF− patients, P = 0.0003). Multivariate analysis identified MF+ as independent predictor of CV mortality [hazard ratio (HR) 27.4 (2.0–369), P = 0.01].Conclusion Histological MF is associated with AS-related pathological LV remodelling and independently predicts CV mortality after TAVI. ]]> <![CDATA[Impact of transcatheter aortic valve implantation on mechanical dispersion]]> https://www.researchpad.co/article/N32ed0aa5-a5ea-40ec-9e9e-e9af8a547f63

Objectives

The physiological determinants of left ventricular (LV) mechanical dispersion (MD) are not fully explored. We aimed to investigate the impact of afterload reduction and changes in ventricular conduction on LV MD after transcatheter aortic valve implantation (TAVI).

Methods

Patients with severe aortic stenosis (AS) were examined in a prospective, repeated measures observational cohort study before and after an uncomplicated transfemoral TAVI in a single tertiary centre. LV MD was assessed by speckle tracking echocardiography. Valvulo-arterial impedance (ZVA) was used as a measure of global afterload.

Results

We included 140 consecutive patients (83±8 years old, 49% women, logistic EuroSCORE 16±10) with severe AS (valve area 0.7±0.2 cm2, mean transvalvular gradient 54±18 mm Hg) and a relatively preserved LV ejection fraction (52%±11%). After TAVI, we observed favourable changes in transvalvular gradients and ZVA in all patients. Compared with baseline, postprocedural MD was significantly lower in 108 patients with unchanged ventricular conduction (55±17 ms vs 51±17 ms, p=0.02) and higher in 28 patients with TAVI-induced left bundle branch block (51±13 ms vs 62±19 ms, p≤0.001). During 22±9 months observation, 22 patients died. Postprocedural MD was associated with mortality in a univariate Cox regression model (HR=1.24 (1.01–1.52), p<0.04, per 10 ms increase).

Conclusions

Isolated afterload reduction was associated with reduction of MD, while concomitant impairment of ventricular conduction resulted in a more pronounced MD after TAVI, indicating that loading conditions and conduction should be considered when evaluating MD. A pronounced postprocedural LV MD was associated with mortality.

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<![CDATA[Lower Blood Pressure After Transcatheter or Surgical Aortic Valve Replacement is Associated with Increased Mortality]]> https://www.researchpad.co/article/Nb574c11b-6f32-48b6-b9b4-a65fd7d33fc3

Background

Blood pressure (BP) guidelines for patients with aortic stenosis or a history of aortic stenosis treated with aortic valve replacement (AVR) match those in the general population, but this extrapolation may not be warranted.

Methods and Results

Among patients enrolled in the Medtronic intermediate, high, and extreme risk trials, we included those with a transcatheter AVR (n=1794) or surgical AVR (n=1103) who were alive at 30 days. The associations between early (average of discharge and 30 day post‐AVR) systolic BP (SBP) and diastolic BP (DBP) measurements and clinical outcomes between 30 days and 1 year were evaluated. Among 2897 patients, after adjustment, spline curves demonstrated an association between lower SBP (<120 mm Hg, representing 21% of patients) and DBP (<60 mm Hg, representing 30% of patients) and increased all‐cause and cardiovascular mortality and repeat hospitalization. These relationships were unchanged when patients with moderate‐to‐severe aortic regurgitation post‐AVR were excluded. After adjustment, compared with DBP 60 to <80 mm Hg, DBP 30 to <60 mm Hg was associated with increased all‐cause (adjusted hazard ratio 1.62, 95% CI 1.23–2.14) and cardiovascular mortality (adjusted hazard ratio 2.13, 95% CI 1.52–3.00), but DBP 80 to <100 mm Hg was not. Similarly, after adjustment, compared with SBP 120 to <150 mm Hg, SBP 90 to <120 mm Hg was associated with increased all‐cause (adjusted hazard ratio 1.63, 95% CI 1.21–2.21) and cardiovascular mortality (adjusted hazard ratio 1.81, 95% CI 1.25–2.61), but SBP 150 to <180 mm Hg was not.

Conclusions

Lower BP in the first month after transcatheter AVR or surgical AVR is common and associated with increased mortality and repeat hospitalization. Clarifying optimal BP targets in these patients ought to be a priority and may improve patient outcomes.

Clinical Trial Registration Information

URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01586910, NCT01240902.

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<![CDATA[Rapid early rise in heart rate on treadmill exercise in patients with asymptomatic moderate or severe aortic stenosis: a new prognostic marker?]]> https://www.researchpad.co/article/5c8ad96cd5eed0c4849a0fd0

Objective

To examine the clinical significance and prognostic value of an early rapid rise in heart rate (RR-HR) in asymptomatic patients with moderate or severe aortic stenosis (AS).

Methods

We retrospectively assessed the prospectively collected data from 306 patients (age 65±12 years, 33% women) with moderate (n=204) or severe AS (n=102) with a median follow-up of 25 months (mean 34.9±34.6 months). All had echocardiography and modified Bruce exercise treadmill tests (ETT). RR-HR was defined as achieving 85% target HR or ≥50% increase from baseline in the first 6 min. The outcome measures were revealed symptoms during ETT, aortic valve replacement (AVR) and all-cause mortality.

Results

RR-HR occurred in 77 (25%) and 64% developed revealed symptoms (postive predictive value 64% and negative predictive value 84%). On univariate Cox regression analyses in patients with severe AS, RR-HR was associated with AVR (HR 3.32, 95% CI 2.03 to 5.45, p<0.001) but not with all-cause mortality (HR 0.04, 95% CI 0.13 to 9.21, p=0.798). In patients with moderate AS, RR-HR was associated with all-cause mortality (HR 2.67, 95% CI 1.09 to 6.56, p=0.032), but not with AVR (HR 1.35, 95% CI 0.92 to 1.98, p=0.127). These associations remained significant in multivariate Cox regression analyses after adjustment for age, sex, hypertension, coronary artery disease, abnormal blood pressure response, Doppler stroke volume and mean pressure gradient (both p<0.001).

Conclusions

RR-HR was associated with the development of revealed symptoms. It predicted revealed symptoms on serial ETT, AVR in severe AS and all-cause mortality in moderate AS. RR-HR may be a useful new measure to define risk in AS.

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<![CDATA[Prevalence and prognostic implication of iron deficiency and anaemia in patients with severe aortic stenosis]]> https://www.researchpad.co/article/5c3947e8d5eed0c484a3e92e

Objective

The aim of this study was to evaluate the prevalence and prognostic implication of iron deficiency (ID) and anaemia in patients with severe aortic stenosis (AS).

Methods

In an observational study of consecutive patients referred for aortic valve replacement (AVR), we assessed a wide range of biomarkers of iron status, including the definition of ID commonly applied in patients with chronic heart failure (ferritin <100 µg/L or ferritin 100–299 µg/L with a transferrin saturation <20%). The endpoints were short-term (one-year) and long-term (median 4.7 years, IQR: 3.8–5.5) mortality and major adverse cardiovascular events (MACE) within the first year after inclusion.

Results

464 patients were included in this substudy. 91 patients (20%) received conservative treatment and 373 patients (80%) received AVR. ID was detected in 246 patients (53%). 94 patients (20%) had anaemia. Patients with ID had an overall worse clinical profile than patients without ID. During follow-up, 129 patients (28%) died. Neither ID as defined above, soluble transferrin receptor nor hepcidin were associated with short-term or long-term mortality or MACE independent on treatment allocation. Anaemia was associated with one-year mortality in conservatively treated patients.

Conclusions

ID and anaemia are prevalent in patients with severe AS. In our cohort, ID did not provide independent prognostic information on top of conventional risk factors. More studies are required to determine how to correctly diagnose ID in patients with AS.

Trial registration number

NCT01794832.

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<![CDATA[Cardiac remodelling and haemodynamic characteristics in primary mitral valve regurgitation]]> https://www.researchpad.co/article/5c3947ccd5eed0c484a3e102

Objective

To assess the association between cardiac morphology and function assessed with cardiac MRI (CMRI) and haemodynamics at rest and during exercise in patients with primary mitral regurgitation (MR).

Methods

In an observational study, subjects with significant primary MR (N = 46) with effective regurgitant orifice ≥ 0.30 cm2 and left ventricular (LV) ejection fraction > 60% were examined with right heart catheterisation during rest and exercise and CMRI at rest. End-diastolic pressure volume relationship (EDPVR) was assessed using a single beat method using pulmonary capillary wedge pressure (PCWP) and end-diastolic volume. Patients were divided according to normal PCWP at rest (> 12 mm Hg) and with exercise (> 28 mm Hg). Results: Resting regurgitant volume correlated positively with resting PCWP, (r = 0.42, p = 0.002). However, with exercise no association between PCWP and regurgitant volume was seen (r = 0.09, p = 0.55). At rest left atrial (LA) maximal, minimal and volume index at atrial contraction correlated positively with PCWP (r = 0.60; r = 0.55; r = 0.58, all p < 0.001); in contrast none of these correlated with exercise PCWP (all p > 0.2). EDPVR in patients with high PCWP at rest was shifted towards higher volumes for the same pressures. The opposite was seen for patients with high PCWP during exercise where estimated volumes were smaller for the same pressure than patients with normal exercise PCWP.

Conclusion

In patients with significant MR the degree of regurgitation and LA dilatation is associated with resting PCWP. However, with exercise this association disappears. Estimation of EDPVR suggests lower LV compliance in patients where PCWP is increased with exercise.

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<![CDATA[Impact of tricuspid regurgitation on postoperative outcomes after non-cardiac surgeries]]> https://www.researchpad.co/article/Nb1494fec-0ad8-47cf-8168-346e5a6be694 Objective
Tricuspid regurgitation (TR) severity has known adverse implications, its impact on patients undergoing non-cardiac surgery (NCS) remains unclear. We sought to determine the impact of TR on patient outcomes after NCS.
Methods
We performed a retrospective cohort study in patients undergoing NCS. Outcomes in patients with moderate or severe TR were compared with no/trivial TR after adjusting for baseline characteristics and revised cardiac risk index (RCRI). The primary outcome was defined as 30-day mortality and heart failure (HF), while the secondary outcome was long-term mortality.
Results
Of the 7064 patients included, 312 and 80 patients had moderate and severe TR, respectively. Thirty-day mortality was higher in moderate TR (adjusted OR 2.44, 95% CI 1.25 to 4.76) and severe TR (OR 2.85, 95% CI 1.04 to 7.79) compared with no/trivial TR. There was no difference in 30-day HF in patients with moderate TR (OR 1.48, 95% CI 0.90 to 2.44) or severe TR (OR 1.42, 95% CI 0.60 to 3.39). The adjusted HR for long-term mortality in moderate TR was 1.55 (95% CI 1.31 to 1.82) and 1.87 (95% CI 1.40 to 2.50) for severe TR compared with no/trivial TR.
Conclusion
Increasing TR severity has higher postoperative 30-day mortality in patients undergoing NCS, independent of RCRI risk factors, ejection fraction or mitral regurgitation. Severity of TR should be considered in risk stratification for patients undergoing NCS.
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<![CDATA[Specialist valve clinic in a cardiac centre: 10-year experience]]> https://www.researchpad.co/article/Nf4b18e89-14b8-4aed-9160-72b60295cdd8 Aims
Guidelines recommend specialist valve clinics as best practice for the assessment and conservative management of patients with heart valve disease. However, there is little guidance on how to set up and organise a clinic. The aim of this study is to describe a clinic run by a multidisciplinary team consisting of cardiologists, physiologist/scientists and a nurse.
Methods
The clinical and organisational aims of the clinic, inclusion and exclusion criteria, and links with other services are described. The methods of training non-clinical staff are detailed. Data were prospectively entered onto a database and the study consisted of an analysis of the clinical characteristics and outcomes of all patients seen between 1 January 2009 and 31 December 2018.
Results
There were 2126 new patients and 9522 visits in the 10-year period. The mean age was 64.8 and 55% were male. Of the visits, 3587 (38%) were to the cardiologists, 4092 (43%) to the physiologist/scientists and 1843 (19%) to the nurse. The outcomes from the cardiologist clinics were cardiology follow-up in 460 (30%), referral for surgery in 354 (23%), referral to the physiologist/scientist clinic in 412 (27%) or to the nurse clinic in 65 (4.3%) and discharge in 230 (15%). The cardiologist needed to see 6% from the nurse clinic and 10% from the physiologist/scientist clinic, while advice alone was sufficient in 10% and 9%.
Conclusion
A multidisciplinary specialist valve clinic is feasible and sustainable in the long term.
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<![CDATA[Dickkopf‐3 Ablation Attenuates the Development of Atherosclerosis in ApoE‐Deficient Mice]]> https://www.researchpad.co/article/5b41e37b463d7e0efe4e0c13

Background

Dickkopf‐3 (DKK3) is a negative regulator of the Wnt/β‐catenin signaling pathway, which is involved in inflammation. However, little is known about the relationship between DKK3 expression and the progression of atherosclerosis. The aim of the present study was to define the role of DKK3 and its potential mechanism in the development of atherosclerosis.

Methods and Results

Immunofluorescence analysis showed that DKK3 was strongly expressed in macrophages of atherosclerotic plaques from patients with coronary heart disease and in hyperlipidemic mice. The expression level was significantly increased in atherogenesis. DKK3−/−ApoE−/− mice exhibited a significant decrease in atherosclerotic lesions in the entire aorta, aortic sinus, and brachiocephalic arteries. Transplantation of bone marrow from DKK3−/−ApoE−/− mice into lethally irradiated ApoE−/− recipients resulted in a reduction of atherosclerotic lesions, compared with the lesions in recipients transplanted with ApoE−/− donor cells, suggesting that the effect of DKK3 deficiency was largely mediated by bone marrow–derived cells. A reduction in the necrotic core size, accompanied by increased collagen content and smooth muscle cells and decreased accumulation of macrophages and lipids, contributed to the stability of plaques in DKK3−/−ApoE−/− mice. Furthermore, multiple proinflammatory cytokines exhibited marked decreases in DKK3−/−ApoE−/− mice. Finally, we observed that DKK3 ablation increased β‐catenin expression in the nuclei of macrophages both in vivo and in vitro.

Conclusions

DKK3 expression in macrophages is involved in the pathogenesis of atherosclerosis through modulation of inflammation and inactivation of the Wnt/β‐catenin pathway.

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<![CDATA[Exercise Treadmill Testing in Moderate or Severe Aortic Stenosis: The Left Ventricular Correlates of an Exaggerated Blood Pressure Rise]]> https://www.researchpad.co/article/5c9bc55cd5eed0c484ee8338

Background

Exaggerated blood pressure response during exercise predicts future hypertension and cardiovascular events in general population and different patients groups. However, its clinical and prognostic implications in patients with aortic stenosis have not been previously evaluated.

Methods and Results

We retrospectively studied 301 patients with moderate to severe asymptomatic aortic stenosis (aged 65±12 years) who underwent echocardiography and a modified Bruce exercise treadmill test. An exaggerated blood pressure response was defined as peak systolic blood pressure ≥190 mm Hg. An abnormal blood pressure response (either blunted or exaggerated) was found in 58% of patients and abnormal left ventricular geometry in 82%. There was no difference in the rates of abnormal blood pressure responses between patients with moderate and severe aortic stenosis ([exaggerated blood pressure response: 21% versus 22%, P=0.876] and [blunted blood pressure response: 35% versus 40%, P=0.647]). Patients with exaggerated blood pressure response (21%) were more likely to be older, have hypertension, higher pretest systolic blood pressure, left ventricular ejection fraction and mass, and increased arterial stiffness (all P<0.05). In a multivariate logistic regression analysis, an exaggerated blood pressure response was associated with higher pulse pressure/stroke volume index (odds ratio 2.45, 95% confidence interval 1.02–6.00, P=0.037) and left ventricular mass (odds ratio 2.04, 95% confidence interval 1.23–3.38, P=0.012) independent of age, hypertension, aortic annulus and left atrium diameter, and left ventricular ejection fraction.

Conclusions

In those with aortic stenosis, exaggerated blood pressure was strongly related to higher resting blood pressure values, left ventricular mass, and increased arterial stiffness independent of hypertension.

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<![CDATA[The value of urotensin II in patients with left-sided rheumatic valvular regurgitation]]> https://www.researchpad.co/article/5bfc34dad5eed0c484de9bb4

Aims

Rheumatic valve diseases are most common etiological valve diseases in developing countries. Urotensin II is cardiovascular autacoid/hormone and may be associated with patients of heart valve diseases. The present study was to measure plasma urotensin II concentrations in patients with left-sided rheumatic valve diseases such as mitral regurgitation (MR) and aortic regurgitation (AR), and to examine its correlation with severity of valve impairment, function (New York Heart association, NYHA) class and pulmonary artery pressure (PAP).

Methods and results

Sixty patients with moderate to severe rheumatic left-sided valve regurgitation and 20 healthy controls were selected after performing the echocardiography. Plasma urotensin II level was measured in all subjects. The patients with MR and AR were significantly increased of left ventricular end diastolic dimension (LVEDD), left ventricular end systolic dimension (LVESD), left atrial diameter, PAP, but decreased of EF% versus the controls. Urotensin II level was highly significant in patients with MR (1.83 ± 0.92 ng/ml, P < 0.001) and AR (0.79 ± 0.3 ng/ml, P < 0.05) versus the controls (0.48 ± 0.13 ng/ml). Also, there was significant correlation between Urotensin II level and LVEDD (MR, r = 0.318, P = 0.03; AR, r = 0.805, P < 0.001), LVESD (MR, r = −0.271, P = 0.115; AR, r = 0.614, P = 0.001), and PAP (MR, r = 0.706, P < 0.001; AR, r = 0.129, P = 0.538).

Conclusion

Urotensin II was elevated in patients with rheumatic left-sided valvular regurgitation, and positively correlated with increased LVEDD (in both MR and AR), LVESD (only AR) and pulmonary artery pressure (only MR). Therefore, urotensin II level may be used as diagnostic biomarker in patients with rheumatic valvular diseases for assessment of the severity in parallel with echocardiography.

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<![CDATA[ MG53 Protein Protects Aortic Valve Interstitial Cells From Membrane Injury and Fibrocalcific Remodeling]]> https://www.researchpad.co/article/5c9d2a61d5eed0c4840aff7f

Background

The aortic valve of the heart experiences constant mechanical stress under physiological conditions. Maladaptive valve injury responses contribute to the development of valvular heart disease. Here, we test the hypothesis that MG53 (mitsugumin 53), an essential cell membrane repair protein, can protect valvular cells from injury and fibrocalcific remodeling processes associated with valvular heart disease.

Methods and Results

We found that MG53 is expressed in pig and human patient aortic valves and observed aortic valve disease in aged Mg53−/− mice. Aortic valves of Mg53−/− mice showed compromised cell membrane integrity. In vitro studies demonstrated that recombinant human MG53 protein protects primary valve interstitial cells from mechanical injury and that, in addition to mediating membrane repair, recombinant human MG53 can enter valve interstitial cells and suppress transforming growth factor‐β‐dependent activation of fibrocalcific signaling.

Conclusions

Together, our data characterize valve interstitial cell membrane repair as a novel mechanism of protection against valvular remodeling and assess potential in vivo roles of MG53 in preventing valvular heart disease.

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