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.

• Klíčová slova
• Collagen, Fibronectin, Fibrosis, Pressure overload, Valvular heart disease,
• 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
• Názvy látek
• extracelulární matrix - proteiny * 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.

• Klíčová slova
• Aortic regurgitation, Asymptomatic, Early surgery, Magnetic resonance, Randomization,
• 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.

• Klíčová slova
• Cardiac resynchronization therapy, Clinical outcomes, Echocardiographic outcomes, Electrically, Guided, Imaging, Latest activation, Targeting left ventricular lead position,
• MeSH
• echokardiografie MeSH
• hospitalizace MeSH
• lidé MeSH
• srdeční komory diagnostické zobrazování   MeSH
• srdeční resynchronizační terapie * škodlivé účinky   MeSH
• srdeční selhání * diagnóza   terapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• systematický přehled 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.

• Klíčová slova
• aortic valve, echocardiography, magnetic resonance imaging, natriuretic peptide, brain, prognosis,
• 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
• práce podpořená grantem MeSH
• Názvy látek
• natriuretický peptid typu B 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.

• Klíčová slova
• aortic stenosis, asymptomatic, intervention, randomized controlled trial,
• 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

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.

• Klíčová slova
• aortic regurgitation, echocardiography, magnetic resonance, quantification, vena contracta,
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: There are no data about the prevalence of silent coronary artery disease in asymptomatic severe aortic stenosis patients with normal exercise testing. Importantly, unmasking significant coronary artery disease in patients with aortic stenosis could influence the choice/timing of treatment in these patients. METHOD: Exercise testing was performed on semi-supine ergobicycle. Cardiopulmonary analysis during exercise testing, echocardiography, and laboratory analysis at rest was done. Standard clinical/electrocardiography criteria were assessed for symptoms/signs of ischemia during/after exercise testing. In patients with normal exercise testing coronary angiography was performed using standard femoral/radial percutaneous approach. Coronary stenosis was considered significant if >70% of vessel diameter or 50%-70% with fractional flow reserve ≤0.8. RESULTS: Total of 96 patients with normal exercise testing were included (67.6 years, 50.6% males). No patient had any complication or adverse event. The Pmean was 52.7 mmHg, mean indexed aortic valve area was 0.36 cm/m and left ventricular ejection fraction, 69.5%. 19/96 patients (19.8%) had significant coronary artery disease on coronary angiography. Multivariate logistic regression analysis revealed brain natriuretic peptide and blood glucose as independent predictors of silent coronary artery disease. Brain natriuretic peptide value of 118 pg/ml had sensitivity/specificity of 63%/73% for predicting coronary artery disease (area under the curve 0.727, P = 0.006). CONCLUSION: Our results are the first to show that in patients with severe aortic stenosis, normal left ventricular ejection fraction,, and normal exercise testing, significant coronary artery disease is present in as many as 1/5 patients. In such patients, further prospective studies are warranted to address the diagnostic value of brain natriuretic peptide in detecting silent coronary artery disease.

• MeSH
• aortální stenóza komplikace   patofyziologie   MeSH
• asymptomatické nemoci * MeSH
• koronární angiografie MeSH
• koronární stenóza komplikace   diagnóza   epidemiologie   metabolismus   MeSH
• krevní glukóza metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• logistické modely MeSH
• natriuretický peptid typu B metabolismus   MeSH
• nemoci koronárních tepen komplikace   diagnóza   epidemiologie   metabolismus   MeSH
• senioři MeSH
• senzitivita a specificita MeSH
• stupeň závažnosti nemoci MeSH
• zátěžový test MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• krevní glukóza MeSH
• natriuretický peptid typu B MeSH

Background: Determining the value of new imaging markers to predict aortic valve (AV) surgery in asymptomatic patients with severe aortic regurgitation (AR) in a prospective, observational, multicenter study. Methods: Consecutive patients with chronic severe AR were enrolled between 2015-2018. Baseline examination included echocardiography (ECHO) with 2- and 3-dimensional (2D and 3D) vena contracta area (VCA), and magnetic resonance imaging (MRI) with regurgitant volume (RV) and fraction (RF) analyzed in CoreLab. Results: The mean follow-up was 587 days (interquartile range (IQR) 296-901) in a total of 104 patients. Twenty patients underwent AV surgery. Baseline clinical and laboratory data did not differ between surgically and medically treated patients. Surgically treated patients had larger left ventricular (LV) dimension, end-diastolic volume (all p < 0.05), and the LV ejection fraction was similar. The surgical group showed higher prevalence of severe AR (70% vs. 40%, p = 0.02). Out of all imaging markers 3D VCA, MRI-derived RV and RF were identified as the strongest independent predictors of AV surgery (all p < 0.001). Conclusions: Parameters related to LV morphology and function showed moderate accuracy to identify patients in need of early AV surgery at the early stage of the disease. 3D ECHO-derived VCA and MRI-derived RV and RF showed high accuracy and excellent sensitivity to identify patients in need of early surgery.

• Klíčová slova
• T1 mapping, aortic regurgitation, echocardiography, longitudinal strain, magnetic resonance imaging, vena contracta area,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Cardiac resynchronization therapy (CRT) improves symptoms of heart failure (HF), morbidity and mortality in selected population. The aim of the study was to investigate the impact of cardiac magnetic resonance (CMR)-guided left ventricular (LV) lead placement on clinical outcomes and LV reverse remodelling in CRT recipients. METHODS: Patients with CRT indication were randomized for CMR-guided (CMR group) or electrophysiologically guided (EP group) LV lead placement between 2011 and 2014. The target site in the CMR group was defined as the most delayed, scar-free, in the EP group as the site with the longest interval between the QRS onset and local electrogram. The primary endpoint was a combination of cardiovascular death or HF hospitalization. Secondary endpoints were New York Heart Association (NYHA) Class improvement ≥1, LV endsystolic diameter reduction >10%, B-type natriuretic peptide reduction by ≥30%. RESULTS: A total of 99 patients (47 in the CMR and 52 in the EP group) were enrolled. During a median follow-up of 47 months, primary composite endpoint occurred in 5 patients in the CMR group and 14 patients in the EP group (HR = 0.46; 95% CI: 0.16-1.32). Patients with left bundle branch block and NYHA Class >2 had better clinical outcome in the CMR group (HR = 0.09; 95% CI: 0.01-0.75). CONCLUSIONS: The use of CMR did not result in significant reduction of combined endpoint of cardiovascular death or HF hospitalization in the total study population. Significant clinical benefit from CMR-guided procedure was observed in a subgroup of optimum CRT candidates with advanced HF.

• Klíčová slova
• Heart failure, Magnetic resonance, Resynchronization therapy, Target segment,
• MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonance kinematografická metody   MeSH
• následné studie MeSH
• prospektivní studie MeSH
• senioři MeSH
• srdeční resynchronizační terapie metody   MeSH
• srdeční selhání diagnostické zobrazování   patofyziologie   terapie   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
• randomizované kontrolované studie MeSH

BACKGROUND: Magnetic resonance imaging (MRI) is an accurate method for the quantitative assessment of organic mitral regurgitation (OMR). The aim of the present study was to compare the discriminative power of MRI quantification and the recommended Doppler echocardiography (ECHO)-derived integrative approach to identify asymptomatic patients with OMR and adverse outcome. METHODS: The study population consisted of 258 asymptomatic patients (63±14 years, 60% men) with preserved left ventricular ejection fraction (>60%) and chronic moderate and severe OMR (flail 25%, prolapse 75%) defined by using the ECHO-derived integrative approach. All patients underwent MRI to quantify regurgitant volume (RV) of OMR by subtracting the aortic forward flow volume from the total left ventricular stroke volume. Severe OMR was defined as RV≥60 mL. RESULTS: Mean ECHO-derived RV was on average 17.1 mL larger than the MRI-derived RV (P<0.05). Concordant grading of OMR severity with both techniques was observed in 197 (76%) individuals with 62 (31%) patients having severe OMR (MRI SEV-ECHO SEV) and 135 (69%) patients having moderate OMR (MRI MOD-ECHO MOD). The remaining 61 (24%) individuals had discordant findings (MRI SEV-ECHO MOD or MRI MOD-ECHO SEV) between the 2 techniques. The majority of these differences in OMR classification were observed in patients with late systolic or multiple jets (both κ<0.2). Patients with eccentric jets showed moderate agreement (κ=0.53; 95% confidence interval, 0.41-0.64). In contrast, a very good agreement (κ=0.90; 95% confidence interval, 0.82-0.98) was observed in a combination of holosystolic, central, and single jet. During a median follow-up of 5.0 years (interquartile range, 3.5-6.0 years), 38 (15%) patients died and 106 (41%) either died or developed indication for mitral valve surgery. In separate Cox regression analyses, the MRI-derived left ventricular end-systolic volume index, RV, and OMR category (severe versus moderate), and the ECHO-derived OMR category were independent predictors of all-cause mortality (all P<0.05). The MRI-derived RV showed the largest area under the curve to predict mortality (0.72) or its combination with the development of indication for mitral valve surgery (0.83). CONCLUSIONS: The findings of the present study suggest that the MRI-derived assessment of OMR can better identify patients with severe OMR and adverse outcome than ECHO-derived integrative approach warranting close follow-up and perhaps, early mitral valve surgery.

• Klíčová slova
• echocardiography, magnetic resonance imaging, mitral valve insufficiency, prognosis, survival,
• MeSH
• dopplerovská echokardiografie * MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie * MeSH
• mitrální chlopeň diagnostické zobrazování   chirurgie   MeSH
• mitrální insuficience diagnóza   mortalita   patologie   MeSH
• plocha pod křivkou MeSH
• prognóza MeSH
• proporcionální rizikové modely MeSH
• reprodukovatelnost výsledků MeSH
• ROC křivka MeSH
• senioři MeSH
• senzitivita a specificita MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH