BACKGROUND AND AIMS: The question of when and how to treat truly asymptomatic patients with severe aortic stenosis (AS) and normal left ventricular (LV) systolic function is still subject to debate and ongoing research. Here, the results of extended follow-up of the AVATAR trial are reported (NCT02436655, ClinicalTrials.gov). METHODS: The AVATAR trial randomly assigned patients with severe, asymptomatic AS and LV ejection fraction ≥ 50% to undergo either early surgical aortic valve replacement (AVR) or conservative treatment with watchful waiting strategy. All patients had negative exercise stress testing. The primary hypothesis was that early AVR will reduce a primary composite endpoint comprising all-cause death, acute myocardial infarction, stroke, or unplanned hospitalization for heart failure (HF), as compared with conservative treatment strategy. RESULTS: A total of 157 low-risk patients (mean age 67 years, 57% men, mean Society of Thoracic Surgeons score 1.7%) were randomly allocated to either the early AVR group (n = 78) or the conservative treatment group (n = 79). In an intention-to-treat analysis, after a median follow-up of 63 months, the primary composite endpoint outcome event occurred in 18/78 patients (23.1%) in the early surgery group and in 37/79 patients (46.8%) in the conservative treatment group [hazard ratio (HR) early surgery vs. conservative treatment 0.42; 95% confidence interval (CI) 0.24-0.73, P = .002]. The Kaplan-Meier estimates for individual endpoints of all-cause death and HF hospitalization were significantly lower in the early surgery compared with the conservative group (HR 0.44; 95% CI 0.23-0.85, P = .012, for all-cause death and HR 0.21; 95% CI 0.06-0.73, P = .007, for HF hospitalizations). CONCLUSIONS: The extended follow-up of the AVATAR trial demonstrates better clinical outcomes with early surgical AVR in truly asymptomatic patients with severe AS and normal LV ejection fraction compared with patients treated with conservative management on watchful waiting.
- MeSH
- aortální chlopeň chirurgie MeSH
- aortální stenóza * chirurgie mortalita terapie MeSH
- asymptomatické nemoci terapie MeSH
- avatar MeSH
- cévní mozková příhoda MeSH
- chirurgická náhrada chlopně * metody MeSH
- hospitalizace statistika a číselné údaje MeSH
- konzervativní terapie * metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- následné studie MeSH
- pozorné vyčkávání MeSH
- senioři MeSH
- tepový objem fyziologie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
- srovnávací studie MeSH
BACKGROUND: The optimal treatment of patients with severe symptomatic aortic regurgitation (AR) is state-of-the-art surgery. Asymptomatic patients with advanced left ventricular (LV) dilatation and/or impaired ejection fraction should undergo surgical treatment, but there is no guidelines consensus on cut-off values for this recommendation. Multimodality imaging has brought new tools for the accurate selection of asymptomatic patients at risk of early clinical deterioration, however, prospective and randomized data are pending. Cardiac magnetic resonance (CMR)-derived AR quantification along with LV remodeling assessment appears to be the most accurate tool for a selection of such patients at risk. TRIAL DESIGN: The objective of our prospective and multicenter study is to determine whether patients at risk of early clinical deterioration as per CMR assessment will benefit from early surgical treatment. The study is designed as a superiority trial to demonstrate that early surgical treatment is safe and more effective than the standard treatment. A total of 217 asymptomatic patients with severe AR, but without current guidelines-based surgical indication, will be enrolled across all centers. We expect 24 % of patients identified as high clinical risk and therefore eligible for 1:1 randomization to early surgical treatment within 3 months or a watchful waiting strategy. Follow-up will be annual. We expect a complete restoration of LV size and function along with improved quality of life and physical performance in a short-term follow-up of 12 months. The primary endpoint will be a composite safety and efficacy with all criteria mandatory: 15 % or larger reduction of baseline CMR-derived LV end-diastolic volume index, LV ejection fraction >50 %, and no major adverse cardiovascular events. The annual follow-up will continue for a minimum of 4 years until the required number of endpoints is achieved to show a statistically significant difference in cardiovascular morbidity and mortality in early surgically treated patients. CONCLUSION: The ELEANOR trial is the first multicenter randomized controlled study to compare early surgical treatment with a watchful waiting strategy in asymptomatic patients with chronic severe AR at high risk of early clinical deterioration as per CMR assessment but without guidelines-based indications for surgical treatment.
- Publikační typ
- časopisecké články MeSH
Valvular heart disease leads to ventricular pressure and/or volume overload. Pressure overload leads to fibrosis, which might regress with its resolution, but the limits and details of this reverse remodeling are not known. To gain more insight into the extent and nature of cardiac fibrosis in valve disease, we analyzed needle biopsies taken from the interventricular septum of patients undergoing surgery for valve replacement focusing on the expression and distribution of major extracellular matrix protein involved in this process. Proteomic analysis performed using mass spectrometry revealed an excellent correlation between the expression of collagen type I and III, but there was little correlation with the immunohistochemical staining performed on sister sections, which included antibodies against collagen I, III, fibronectin, sarcomeric actin, and histochemistry for wheat germ agglutinin. Surprisingly, the immunofluorescence intensity did not correlate significantly with the gold standard for fibrosis quantification, which was performed using Picrosirius Red (PSR) staining, unless multiplexed on the same tissue section. There was also little correlation between the immunohistochemical markers and pressure gradient severity. It appears that at least in humans, the immunohistochemical pattern of fibrosis is not clearly correlated with standard Picrosirius Red staining on sister sections or quantitative proteomic data, possibly due to tissue heterogeneity at microscale, comorbidities, or other patient-specific factors. For precise correlation of different types of staining, multiplexing on the same section is the best approach.
- MeSH
- aortální insuficience metabolismus patologie chirurgie MeSH
- aortální stenóza * metabolismus patologie chirurgie MeSH
- extracelulární matrix - proteiny * metabolismus analýza MeSH
- fibróza * metabolismus patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mezikomorová přepážka patologie metabolismus MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
AIMS: Several studies have evaluated the use of electrically- or imaging-guided left ventricular (LV) lead placement in cardiac resynchronization therapy (CRT) recipients. We aimed to assess evidence for a guided strategy that targets LV lead position to the site of latest LV activation. METHODS AND RESULTS: A systematic review and meta-analysis was performed for randomized controlled trials (RCTs) until March 2023 that evaluated electrically- or imaging-guided LV lead positioning on clinical and echocardiographic outcomes. The primary endpoint was a composite of all-cause mortality and heart failure hospitalization, and secondary endpoints were quality of life, 6-min walk test (6MWT), QRS duration, LV end-systolic volume, and LV ejection fraction. We included eight RCTs that comprised 1323 patients. Six RCTs compared guided strategy (n = 638) to routine (n = 468), and two RCTs compared different guiding strategies head-to-head: electrically- (n = 111) vs. imaging-guided (n = 106). Compared to routine, a guided strategy did not significantly reduce the risk of the primary endpoint after 12-24 (RR 0.83, 95% CI 0.52-1.33) months. A guided strategy was associated with slight improvement in 6MWT distance after 6 months of follow-up of absolute 18 (95% CI 6-30) m between groups, but not in remaining secondary endpoints. None of the secondary endpoints differed between the guided strategies. CONCLUSION: In this study, a CRT implantation strategy that targets the latest LV activation did not improve survival or reduce heart failure hospitalizations.
- MeSH
- diagnostické techniky kardiovaskulární MeSH
- echokardiografie metody MeSH
- fibróza diagnostické zobrazování MeSH
- kardiologické zobrazovací techniky * MeSH
- kardiomyopatie diagnostické zobrazování MeSH
- koronární angiografie metody MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- myokarditida diagnostické zobrazování MeSH
- nemoci srdečních chlopní diagnostické zobrazování MeSH
- počítačová rentgenová tomografie metody MeSH
- SPECT/CT metody MeSH
- srdeční selhání * diagnostické zobrazování MeSH
- zátěžová echokardiografie metody MeSH
- Check Tag
- lidé MeSH
BACKGROUND: Use of the current echocardiography-based indications for aortic regurgitation (AR) surgery might result in late valve replacement at the stage of irreversible myocardial damage. Therefore, we aimed to identify simple models combining multiple echocardiography or magnetic resonance imaging (MRI)-derived indices and natriuretic peptides (BNP [brain natriuretic peptide] or NT-proBNP [N-terminnal pro-B type natriuretic peptide]) to predict early disease decompensation in asymptomatic severe AR. METHODS: This prospective and multicenter study included asymptomatic patients with severe AR, preserved left ventricular ejection fraction (>50%), and sinus rhythm. The echocardiography and MRI images were analyzed centrally in the CoreLab. The study end point was the onset of indication for aortic valve surgery as per current guidelines. RESULTS: The derivative cohort consisted of 127 asymptomatic patients (age 45±14 years, 84% males) with 41 (32%) end points during a median follow-up of 1375 (interquartile range, 1041-1783) days. In multivariable Cox regression analysis, age, BNP, 3-dimensional vena contracta area, MRI left ventricular end-diastolic volume index, regurgitant volume, and a fraction were identified as independent predictors of end point (all P<0.05). However, a combined model including one parameter of AR assessment (MRI regurgitant volume or regurgitant fraction or 3-dimensional vena contracta area), 1 parameter of left ventricular remodeling (MRI left ventricular end-diastolic volume index or echocardiography 2-dimensional global longitudinal strain or E wave), and BNP showed significantly higher predictive accuracy (area under the curve, 0.74-0.81) than any parameter alone (area under the curve, 0.61-0.72). These findings were confirmed in the validation cohort (n=100 patients, 38 end points). CONCLUSIONS: In asymptomatic severe AR, multimodality and multiparametric model combining 2 imaging indices with natriuretic peptides, showed high accuracy to identify early disease decompensation. Further prospective studies are warranted to explore the clinical benefit of implementing these models to guide patient management. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02910349.
- MeSH
- aortální insuficience * diagnostické zobrazování etiologie chirurgie MeSH
- dospělí MeSH
- echokardiografie MeSH
- funkce levé komory srdeční MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- natriuretický peptid typu B MeSH
- tepový objem MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
Dilatace kořene a/nebo ascendentní aorty je spjata s vyšším rizikem akutní disekce. U nemocných bez chlopenní vady, kteří nesplňují kritéria pro její náhradu, byla v posledních letech zavedena do praxe metoda PEARS (personalized external aortic root support). Spočívá v implantaci na míru vyrobené dakronové síťky, která zabrání progresi dilatace aorty. V práci jsou prezentovány výsledky prvních 100 implantací této síťky u pacientů v České republice. Soubor nemocných a metodika: Soubor tvořilo 77 mužů a 23 žen, průměrného věku 40,4 ± 15,3 roku. U 87 pacientů byla prokázána geneticky podmíněná aortopatie (porucha pojivové tkáně a/nebo bikuspidální aortální chlopeň). U 14 pacientů byla aortální regurgitace větší než 1. st, ale u žádného větší než 2. st. Maximální rozměry aortálního kořene a ascendentní aorty byly 60, resp. 59 mm. Výsledky: U všech pacientů byla síťka úspěšně implantována, u 35 za srdeční akce bez mimotělního oběhu. V časném pooperačním průběhu byly u 35 pacientů přítomny klinické nebo laboratorní známky zánětu, u 23 pacientů přechodné supraventrikulární poruchy srdečního rytmu. Průměrná doba hospitalizace činila 8,4 ± 2,4 dne a žádný pacient v časném pooperačním průběhu nezemřel. Pacienti byli sledováni v průměru 18,1 ± 17,2 měsíce a na kontrolním vyšetření došlo ve srovnání s předoperačními hodnotami k signifikantnímu zmenšení rozměrů kořene, sinotubulární junkce i ascendentní aorty. Závěr: Střednědobé sledování pacientů s dilatací aorty po implantaci PEARS ukázalo, že tato metoda brání dilataci aorty a je dobrým preventivním opatřením před možnou aortální disekcí.
Dilatation of the aortic root and/or ascending aorta is associated with an increased risk of acute dissection. Personalized external aortic root support (PEARS) is a new method that was introduced in last years for these patients without any significant valve disease who do not fulfil the criteria for aortic root or ascending aorta replacement. It is a custom-made macroporous mesh that stabilises the aortic wall. We present the results of the first 100 consecutive patients in whom PEARS was implanted.
- MeSH
- chirurgické síťky MeSH
- disekce aorty * chirurgie MeSH
- lidé MeSH
- retrospektivní studie MeSH
- Check Tag
- lidé MeSH
BACKGROUND: Surgical aortic valve replacement (SAVR) represents a class I indication in symptomatic patients with severe aortic stenosis (AS). However, indications for early SAVR in asymptomatic patients with severe AS and normal left ventricular function remain debated. METHODS: The AVATAR trial (Aortic Valve Replacement Versus Conservative Treatment in Asymptomatic Severe Aortic Stenosis) is an investigator-initiated international prospective randomized controlled trial that evaluated the safety and efficacy of early SAVR in the treatment of asymptomatic patients with severe AS, according to common criteria (valve area ≤1 cm2 with aortic jet velocity >4 m/s or a mean transaortic gradient ≥40 mm Hg), and with normal left ventricular function. Negative exercise testing was mandatory for inclusion. The primary hypothesis was that early SAVR would reduce the primary composite end point of all-cause death, acute myocardial infarction, stroke, or unplanned hospitalization for heart failure compared with a conservative strategy according to guidelines. The trial was designed as event-driven to reach a minimum of 35 prespecified events. The study was performed in 9 centers in 7 European countries. RESULTS: Between June 2015 and September 2020, 157 patients (mean age, 67 years; 57% men) were randomly allocated to early surgery (n=78) or conservative treatment (n=79). Follow-up was completed in May 2021. Overall median follow-up was 32 months: 28 months in the early surgery group and 35 months in the conservative treatment group. There was a total of 39 events, 13 in early surgery and 26 in the conservative treatment group. In the early surgery group, 72 patients (92.3%) underwent SAVR with operative mortality of 1.4%. In an intention-to-treat analysis, patients randomized to early surgery had a significantly lower incidence of primary composite end point than those in the conservative arm (hazard ratio, 0.46 [95% CI, 0.23-0.90]; P=0.02). There was no statistical difference in secondary end points, including all-cause mortality, first heart failure hospitalizations, major bleeding, or thromboembolic complications, but trends were consistent with the primary outcome. CONCLUSIONS: In asymptomatic patients with severe AS, early surgery reduced a primary composite of all-cause death, acute myocardial infarction, stroke, or unplanned hospitalization for heart failure compared with conservative treatment. This randomized trial provides preliminary support for early SAVR once AS becomes severe, regardless of symptoms. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02436655.
- MeSH
- aortální stenóza mortalita terapie MeSH
- chirurgická náhrada chlopně * MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- následné studie MeSH
- prospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- srdeční chlopně umělé * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
- srovnávací studie MeSH
Závěrečná zpráva o řešení grantu Agentury pro zdravotnický výzkum MZ ČR
nestr.
Významná aortální regurgitace je běžnou chlopenní vadou s prevalencí cca 1%, která postihuje častěji mladší jedince v produktivním věku. Jedinou kauzální léčbou této chlopenní vady je chirurgický výkon, který je indikován u pacientů s významnou symptomatickou aortální regurgitací. Správné načasování chirurgické léčby je zásadní, protože je zatížena mortalitním rizikem a většinou přináší nutnost doživotní antikoagulační léčby. Je známo, že asymptomatičtí pacienti s těžkou dilatací a systolickou dysfunkcí levé komory mají pooperačně horší prognózu. Cílem naší práce je hodnotit nativní T1 relaxační čas myokardu měřený magnetickou rezonancí a hodnoty globálního longitudinálního strainu levé komory, jejichž změny korelují se stupněm difúzní fibrózy myokardu. Předpokládáme, že identifikujeme cut off hodnoty těchto parametrů, které budou odpovídat dalšímu klinickému vývoji chlopenní vady a umožní lepší načasování chirurgického výkonu tak, aby došlo k optimální pooperační reverzní remodelaci levé komory a dlouhodobá prognóza pacientů byla co nejlepší.; Severe aortic regurgitation is a common valvular heart disease with prevalence of approximately 1%, affecting rather younger patients. The surgical treatment is the only causal treatment; it is recommended in patients with severe symptomatic aortic regurgitation. The optimal timing of the surgery is crucial because there is a certain risk of perioperative mortality and most patients require lifelong anticoagulation therapy. It is widely accepted, that asymptomatic patients with severely dilated left ventricle with systolic impairment have worse postoperative prognosis. We aim to evaluate native myocardial T1 relaxation time derived from cardiac magnetic resonance and global longitudinal left ventricular strain measured by echocardiography. These parameters are related to diffuse myocardial fibrosis and we expect to identify the cut off values, which correlate with further clinical course. This might enable better timing of the surgical treatment with the optimal postoperative left ventricular reverse remodelling and improved patient prognosis.
- MeSH
- aortální insuficience diagnostické zobrazování MeSH
- echokardiografie MeSH
- fibróza MeSH
- globální longitudinální strain MeSH
- magnetická rezonanční tomografie MeSH
- myokard patologie MeSH
- zobrazování trojrozměrné MeSH
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- kardiologie
- radiologie, nukleární medicína a zobrazovací metody
- NLK Publikační typ
- závěrečné zprávy o řešení grantu AZV MZ ČR
Reliable quantification of aortic regurgitation (AR) severity is essential for clinical management. We aimed to compare quantitative and indirect echo-Doppler indices to quantitative cardiac magnetic resonance (CMR) parameters in asymptomatic chronic severe AR. Methods and Results: We evaluated 104 consecutive patients using echocardiography and CMR. A comprehensive 2D, 3D, and Doppler echocardiography was performed. The CMR was used to quantify regurgitation fraction (RF) and volume (RV) using the phase-contrast velocity mapping technique. Concordant grading of AR severity with both techniques was observed in 77 (74%) patients. Correlation between RV and RF as assessed by echocardiography and CMR was relatively good (rs = 0.50 for RV, rs = 0.40 for RF, p < 0.0001). The best correlation between indirect echo-Doppler and CMR parameters was found for diastolic flow reversal (DFR) velocity in descending aorta (rs = 0.62 for RV, rs = 0.50 for RF, p < 0.0001) and 3D vena contracta area (VCA) (rs = 0.48 for RV, rs = 0.38 for RF, p < 0.0001). Using receiver operating characteristic analysis, the largest area under curve (AUC) to predict severe AR by CMR RV was observed for DFR velocity (AUC = 0.79). DFR velocity of 19.5 cm/s provided 78% sensitivity and 80% specificity. The AUC for 3D VCA to predict severe AR by CMR RV was 0.73, with optimal cut-off of 26 mm2 (sensitivity 80% and specificity 66%). Conclusions: Out of the indirect echo-Doppler indices of AR severity, DFR velocity in descending aorta and 3D vena contracta area showed the best correlation with CMR-derived RV and RF in patients with chronic severe AR.
- Publikační typ
- časopisecké články MeSH