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      Antihypertensive therapies in moderate or severe aortic stenosis: a systematic review and meta-analysis

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          Abstract

          Background

          Hypertension confers a poor prognosis in moderate or severe aortic stenosis (AS), however, antihypertensive therapy (AHT) is often not prescribed due to the perceived deleterious effects of vasodilation and negative inotropes.

          Objective

          To assess the efficacy and safety outcomes of AHT in adults with moderate or severe AS.

          Design

          Systematic review and meta-analysis.

          Data sources

          The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and grey literature were searched without language restrictions up to 9 September 2019.

          Study eligibility criteria, appraisal and synthesis methods

          Two independent reviewers performed screening, data extraction and risk of bias assessments from a systematic search of observational studies and randomised controlled trials comparing AHT with a placebo or no AHT in adults with moderate or severe AS for any parameter of efficacy and safety outcomes. Conflicts were resolved by the third reviewer. Meta-analysis with pooled effect sizes using random-effects model, were estimated in R.

          Main outcome measures

          Mortality, Left Ventricular (LV) Mass Index, systolic blood pressure, diastolic blood pressure and LV ejection fraction

          Results

          From 3025 publications, 31 studies (26 500 patients) were included in the qualitative synthesis and 24 studies in the meta-analysis. AHT was not associated with mortality when all studies were pooled, but heterogeneity was substantial across studies. The effect size of AHT differed according to drug class. Renin–angiotensin–aldosterone system inhibitors (RAASi) were associated with reduced risk of mortality (Pooled HR 0.58, 95% CI 0.43 to 0.80, p=0.006), The differences in changes of haemodynamic or echocardiographic parameters from baseline with and without AHT did not reach statistical significance.

          Conclusion

          AHT appears safe, is well tolerated. RAASi were associated with clinical benefit in patients with moderate or severe AS.

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          Most cited references 66

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          Transcatheter aortic valve implantation for the treatment of severe symptomatic aortic stenosis in patients at very high or prohibitive surgical risk: acute and late outcomes of the multicenter Canadian experience.

          The aim of this study was: 1) to evaluate the acute and late outcomes of a transcatheter aortic valve implantation (TAVI) program including both the transfemoral (TF) and transapical (TA) approaches; and 2) to determine the results of TAVI in patients deemed inoperable because of either porcelain aorta or frailty. Very few data exist on the results of a comprehensive TAVI program including both TA and TF approaches for the treatment of severe aortic stenosis in patients at very high or prohibitive surgical risk. Consecutive patients who underwent TAVI with the Edwards valve (Edwards Lifesciences, Inc., Irvine, California) between January 2005 and June 2009 in 6 Canadian centers were included. A total of 345 procedures (TF: 168, TA: 177) were performed in 339 patients. The predicted surgical mortality (Society of Thoracic Surgeons risk score) was 9.8 +/- 6.4%. The procedural success rate was 93.3%, and 30-day mortality was 10.4% (TF: 9.5%, TA: 11.3%). After a median follow-up of 8 months (25th to 75th interquartile range: 3 to 14 months) the mortality rate was 22.1%. The predictors of cumulative late mortality were peri-procedural sepsis (hazard ratio [HR]: 3.49, 95% confidence interval [CI]: 1.48 to 8.28) or need for hemodynamic support (HR: 2.58, 95% CI: 1.11 to 6), pulmonary hypertension (PH) (HR: 1.88, 95% CI: 1.17 to 3), chronic kidney disease (CKD) (HR: 2.30, 95% CI: 1.38 to 3.84), and chronic obstructive pulmonary disease (COPD) (HR: 1.75, 95% CI: 1.09 to 2.83). Patients with either porcelain aorta (18%) or frailty (25%) exhibited acute outcomes similar to the rest of the study population, and porcelain aorta patients tended to have a better survival rate at 1-year follow-up. A TAVI program including both TF and TA approaches was associated with comparable mortality as predicted by surgical risk calculators for the treatment of patients at very high or prohibitive surgical risk, including porcelain aorta and frail patients. Baseline (PH, COPD, CKD) and peri-procedural (hemodynamic support, sepsis) factors but not the approach determined worse outcomes. Copyright 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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            Clinical profile and natural history of 453 nonsurgically managed patients with severe aortic stenosis.

            Severe aortic stenosis (AS) is a surgically correctable condition. However, aortic valve replacement (AVR) is not offered to many patients with severe AS for various reasons. We investigated the profile and survival patterns of patients with severe AS who did not have AVR. Our echocardiographic database was screened for patients with severe AS, defined as a Doppler estimated aortic valve area of 0.8 cm2 or less between 1993 and 2003. Seven hundred and forty patients with severe AS were identified, of whom 453 patients had no AVR through the follow-up period, forming the study cohort. These patients were comprehensively characterized by obtaining clinical, pharmacologic, and surgical data through a comprehensive chart review and extracting survival data from the National Death Index. Patient characteristics were as follows: age 75 +/- 13 years, 48% male, left ventricular (LV) ejection fraction 52 +/- 21%, coronary artery disease in 34%, hypertension in 35%, serum creatinine level greater than 2 mg/dL in 11%, and diabetes mellitus in 14%. The survival at 1 year, 5 years, and 10 years was 62%, 32%, and 18%, respectively. The univariate predictors of reduced survival were advanced age, low LV ejection fraction, heart failure, elevated serum creatinine level, severe mitral regurgitation, and pulmonary hypertension; and the independent predictors were advanced age, low LV ejection fraction, heart failure, elevated serum creatinine level, and systemic hypertension. Concomitant pharmacotherapy had no impact on survival. Conservatively treated patients with severe AS have a grave prognosis, and it is worse in the presence of advanced age, LV dysfunction, heart failure, and renal failure.
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              New concepts in diastolic dysfunction and diastolic heart failure: Part II: causal mechanisms and treatment.

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                Author and article information

                Journal
                BMJ Open
                BMJ Open
                bmjopen
                bmjopen
                BMJ Open
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                2044-6055
                2020
                5 October 2020
                : 10
                : 10
                Affiliations
                [1 ]Baker Heart and Diabetes Institute , Melbourne, Victoria, Australia
                [2 ]departmentFaculty of Medicine, Dentistry and Health Sciences , University of Melbourne , Melbourne, Victoria, Australia
                [3 ]departmentGraduate Department of Pharmaceutical Sciences , University of Toronto , Toronto, Ontario, Canada
                Author notes
                [Correspondence to ] Dr Thomas Marwick; tom.marwick@ 123456bakeridi.edu.au
                Article
                bmjopen-2020-036960
                10.1136/bmjopen-2020-036960
                7537451
                33020089
                © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:  http://creativecommons.org/licenses/by-nc/4.0/.

                Product
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100000925, National Health and Medical Research Council;
                Award ID: 1149692
                Funded by: National Health and Medical Research Council of Australia;
                Award ID: ID: 1191044
                Funded by: National Heart Foundation of Australia;
                Award ID: ID: 102578
                Categories
                Cardiovascular Medicine
                1506
                1683
                Original research
                Custom metadata
                unlocked

                Medicine

                adult cardiology, hypertension, valvular heart disease

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