Fabry disease is a progressive, X-linked lysosomal disorder caused by reduced or absent α-galactosidase A activity due to GLA variants. The effects of migalastat were examined in a cohort of 125 Fabry patients with migalastat-amenable GLA variants in the followME Pathfinders registry (EUPAS20599), an ongoing, prospective, patient-focused registry evaluating outcomes for current Fabry disease treatments. We report annualised estimated glomerular filtration rate (eGFR) and Fabry-associated clinical events (FACEs) in a cohort of patients who had received ≥3 years of migalastat treatment in a real-world setting. As of August 2022, 125 patients (60% male) had a mean migalastat exposure of 3.9 years. At enrolment, median age was 58 years (males, 57; females, 60) with a mean eGFR of 83.7 mL/min/1.73 m2 (n = 122; males, 83.7; females, 83.8) and a median left ventricular mass index of 115.1 g/m2 (n = 61; males, 131.2; females, 98.0). Mean (95% confidence interval) eGFR annualised rate of change in the overall cohort (n = 116) was -0.9 (-10.8, 9.9) mL/min/1.73 m2/year with a similar rate of change observed across patients with varying levels of kidney function at enrolment. Despite population age and baseline morbidity, 80% of patients did not experience a FACE during the mean 3.9 years of migalastat exposure. The incidence of renal, cardiac, and cerebrovascular events was 2.0, 83.2, and 4.1 events per 1000 patient-years, respectively. These data support a role of migalastat in preserving renal function and multisystem effectiveness during ≥3 years of migalastat treatment in this real-world Fabry population.

• Klíčová slova
• Fabry disease, migalastat, real world evidence,
• MeSH
• 1-deoxynojirimycin * analogy a deriváty   terapeutické užití   MeSH
• alfa-galaktosidasa genetika   MeSH
• dospělí MeSH
• Fabryho nemoc * farmakoterapie   komplikace   MeSH
• hodnoty glomerulární filtrace účinky léků   MeSH
• kohortové studie MeSH
• ledviny účinky léků   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prospektivní studie MeSH
• registrace MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 1-deoxynojirimycin * MeSH
• alfa-galaktosidasa MeSH
• migalastat MeSH Prohlížeč

BACKGROUND: Left bundle branch pacing (LBBP) is a novel physiological pacing technique which may serve as an alternative to cardiac resynchronization therapy (CRT) by biventricular pacing (BVP). This study assessed ventricular activation patterns and echocardiographic and clinical outcomes of LBBP and compared this to BVP. METHODS: Fifty consecutive patients underwent LBBP or BVP for CRT. Ventricular activation mapping was obtained by ultra-high-frequency ECG (UHF-ECG). Functional and echocardiographic outcomes and hospitalization for heart failure and all-cause mortality after one year from implantation were evaluated. RESULTS: LBBP resulted in greater resynchronization vs BVP (QRS width: 170 ± 16 ms to 128 ± 20 ms vs 174 ± 15 to 144 ± 17 ms, p = 0.002 (LBBP vs BVP); e-DYS 81 ± 17 ms to 0 ± 32 ms vs 77 ± 18 to 16 ± 29 ms, p = 0.016 (LBBP vs BVP)). Improvement in LVEF (from 28 ± 8 to 42 ± 10 percent vs 28 ± 9 to 36 ± 12 percent, LBBP vs BVP, p = 0.078) was similar. Improvement in NYHA function class (from 2.4 to 1.5 and from 2.3 to 1.5 (LBBP vs BVP)), hospitalization for heart failure and all-cause mortality were comparable in both groups. CONCLUSIONS: Ventricular dyssynchrony imaging is an appropriate way to gain a better insight into activation patterns of LBBP and BVP. LBBP resulted in greater resynchronization (e-DYS and QRS duration) with comparable improvement in LVEF, NYHA functional class, hospitalization for heart failure and all-cause mortality at one year of follow up.

• Klíčová slova
• Biventricular pacing, Cardiac resynchronization therapy, Left bundle branch pacing, Ventricular activation mapping,
• Publikační typ
• časopisecké články MeSH

AIMS: Physical activity (PA) is an important target for improving clinical outcomes in heart failure (HF) patients. Nonetheless, assessing the daily PA profile in this population is a challenging task, traditionally performed using self-report questionnaires such as the International PA Questionnaire Short Form (IPAQ-SF). This study aimed to evaluate the concurrent validity of the IPAQ-SF and accelerometer-assessed PA using six published cut-points in patients with HF and reduced or mildly reduced ejection fraction. METHODS AND RESULTS: The concordance between the IPAQ-SF and a hip-worn accelerometer regarding daily time spent performing moderate to vigorous PA in bouts of at least 10 min was assessed in 53 participants for seven consecutive days using six different cut-points (Barnett, Dibben, Mark, Sanders, Troiano, and Vaha-Ypya). Spearman's correlation and Bland-Altman plots were used to evaluate concurrent validity between methods. Regressions were used to study the association between patient variables, wear protocol (waking hour or 24 h), and absolute bias. The kappa index was used to evaluate the concordance between IPAQ-SF and accelerometry for classifying patients as active or non-active. All analyses were re-run using non-bouted metrics to investigate the effect of bouted versus non-bouted analysis. The IPAQ-SF and accelerometry showed low to negligible correlation (ρ = 0.12 to 0.37), depending on the cut-point used. The regression analysis showed that the absolute bias was higher in participants following the waking-hour protocol at all cut-points except Dibben's (P ≤ 0.007). The concordance between the two methods to classify patients as active and non-active was low when using Mark (κ = 0.23) and Barnett (κ = 0.34) cut-points and poor for the remaining cut-points (κ = 0.03 to 0.18). The results of the sensitivity analysis showed negligible to low correlation using non-bouted metrics (ρ = 0.27 to 0.33). CONCLUSIONS: Moderate to vigorous PA measures using IPAQ-SF and accelerometers are not equivalent, and we do not encourage researchers to use IPAQ-SF alone when assessing PA in HF patients. Moreover, applying personalized collection and processing criteria is important when assessing PA in HF patients. We recommend following the 24 h protocol and selecting cut-points calibrated in patients with cardiovascular diseases. Finally, it is necessary to develop a new tailored questionnaire that considers walking intensity and is adjusted to the current World Health Organisation recommendations, which use non-bouted metrics.

• Klíčová slova
• Activity monitor, Agreement, Device-based measures, HF, MVPA, Self-reported measures,
• MeSH
• akcelerometrie MeSH
• cvičení * MeSH
• lidé MeSH
• průzkumy a dotazníky MeSH
• srdeční selhání * diagnóza   MeSH
• zpráva o sobě MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

AIMS: Fabry disease (FD) is a multisystemic lysosomal storage disorder caused by a defect in the alpha-galactosidase A gene that manifests as a phenocopy of hypertrophic cardiomyopathy. We assessed the echocardiographic 3D left ventricular (LV) strain of patients with FD in relation to heart failure severity using natriuretic peptides, the presence of a cardiovascular magnetic resonance (CMR) late gadolinium enhancement scar, and long-term prognosis. METHODS AND RESULTS: 3D echocardiography was feasible in 75/99 patients with FD [aged 47 ± 14 years, 44% males, LV ejection fraction (EF) 65 ± 6% and 51% with hypertrophy or concentric remodelling of the LV]. Long-term prognosis (death, heart failure decompensation, or cardiovascular hospitalization) was assessed over a median follow-up of 3.1 years. A stronger correlation was observed for N-terminal pro-brain natriuretic peptide levels with 3D LV global longitudinal strain (GLS, r = -0.49, P < 0.0001) than with 3D LV global circumferential strain (GCS, r = -0.38, P < 0.001) or 3D LVEF (r = -0.25, P = 0.036). Individuals with posterolateral scar on CMR had lower posterolateral 3D circumferential strain (CS; P = 0.009). 3D LV-GLS was associated with long-term prognosis [adjusted hazard ratio 0.85 (confidence interval 0.75-0.95), P = 0.004], while 3D LV-GCS and 3D LVEF were not (P = 0.284 and P = 0.324). CONCLUSION: 3D LV-GLS is associated with both heart failure severity measured by natriuretic peptide levels and long-term prognosis. Decreased posterolateral 3D CS reflects typical posterolateral scarring in FD. Where feasible, 3D-strain echocardiography can be used for a comprehensive mechanical assessment of the LV in patients with FD.

• Klíčová slova
• 3D echocardiography, Fabry disease, cardiovascular magnetic resonance, heart failure, myocardial strain,
• MeSH
• dysfunkce levé srdeční komory * diagnostické zobrazování   etiologie   MeSH
• echokardiografie trojrozměrná * metody   MeSH
• echokardiografie metody   MeSH
• Fabryho nemoc * komplikace   diagnostické zobrazování   MeSH
• funkce levé komory srdeční MeSH
• gadolinium MeSH
• jizva diagnostické zobrazování   MeSH
• kontrastní látky MeSH
• lidé MeSH
• prognóza MeSH
• reprodukovatelnost výsledků MeSH
• srdeční selhání * diagnostické zobrazování   etiologie   MeSH
• tepový objem MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• gadolinium MeSH
• kontrastní látky MeSH

There is no biomarker reflecting right ventricular dysfunction in HFrEF patients used in clinical practice. We have aimed to look for a circulating marker of RV dysfunction employing a quantitative proteomic strategy. The Olink Proteomics Multiplex panels (Cardiovascular Disease II, III, Cardiometabolic, and Inflammation Target Panels) identified FGF-23 to be the most differentially abundant (more than 2.5-fold) in blood plasma of HF patients with severe RV dysfunction (n = 30) compared to those with preserved RV function (n = 31). A subsequent ELISA-based confirmatory analysis of circulating FGF-23 in a large cohort of patients (n = 344, 72.7% NYHA III/IV, LVEF 22.5%, 54.1% with moderate/severe RV dysfunction), followed by multivariable regression analysis, revealed that the plasma FGF-23 level was most significantly associated with RV dysfunction grade (p = 0.0004) and congestion in the systemic circulation (p = 0.03), but not with LV-ejection fraction (p = 0.69) or estimated glomerular filtration rate (eGFR, p = 0.08). FGF-23 was associated with the degree of RV dysfunction in both sub-cohorts (i.e. in patients with and without congestion, p < 0.0001). The association between FGF-23 and RV-dysfunction remained significant after the adjustment for BNP (p = 0.01). In contrast, when adjusted for BNP, FGF-23 was no longer associated with LV dysfunction (p = 0.59). The Cox proportional hazard model revealed that circulating FGF-23 was significantly associated with adverse outcomes even after adjusting for BNP, LVEF, RV dysfunction grade and eGFR. Circulating FGF-23 is thus a biomarker of right ventricular dysfunction in HFrEF patients regardless of congestion status.

• MeSH
• biologické markery MeSH
• dysfunkce pravé srdeční komory * MeSH
• funkce levé komory srdeční MeSH
• lidé MeSH
• prognóza MeSH
• proteomika MeSH
• srdeční selhání * MeSH
• tepový objem MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH

The impact of atrial fibrillation and atrial tachycardias (AF/AT), and their optimal treatment strategy in PH patients is still being discussed. The goal of this study was to evaluate the effect of AF/AT termination on the hemodynamic parameters in PH patients. We compared patients with pre-capillary pulmonary hypertension (PH group), left ventricular heart failure (LV-HF group), and a Control group. A repeated right heart catheterization was performed during the catheter ablation (CA) procedure. The first measurement was done in arrhythmia, the second after the sinus rhythm (SR) was restored. High frequency atrial stimulation was used to simulate AT in patients without arrhythmia presence at the time of the CA. The variation of pressure parameters in PH patients did not differ significantly from the Controls. There was a significant increase in the right ventricle pressure after the SR restoration in the LV-HF group compared to the Controls and PH group (+4 vs. -2 vs. -3 mmHg, p<0.05). The cardiac index (CI) variation was not significant when compared between the study groups. An increase of the CI after the SR restoration was found in those patients with AF (+0.31 l/min/m2 [IQR 0.18; 0.58]) in contrast to those patients with organized AT/high frequency atrial stimulation ( 0.09 l/min/m2, [IQR - 0.45; 0.19]). This difference was statistically significant (p<0.05). The acute hemodynamic response to arrhythmia termination was not significantly different in the PH patients when compared to the Controls. In contrast to AT/high frequency stimulation, the restoration of SR in AF patients leads to an increased CI, irrespective of the presence or absence of PH.

• MeSH
• fibrilace síní * diagnóza   chirurgie   etiologie   MeSH
• hemodynamika MeSH
• katetrizační ablace * metody   MeSH
• lidé MeSH
• plicní hypertenze * diagnóza   MeSH
• srdeční selhání * MeSH
• srdeční síně chirurgie   MeSH
• tachykardie etiologie   chirurgie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

AIMS: Fabry disease (FD) is often associated with heart failure (HF). However, data on HF prevalence, prognosis, and applicability of echocardiographic criteria for HF diagnosis in FD remain uncertain. METHODS AND RESULTS: We evaluated patients with genetically proven FD for symptoms and natriuretic peptides indicating HF. We then analysed the diagnostic utility of the currently recommended European Society of Cardiology (ESC) echocardiographic criteria for HF diagnosis and their relationship to natriuretic peptides. Finally, we examined the association between HF and echocardiographic criteria with mortality and cardiovascular events during follow-up. Of 116 patients with FD, 48 (41%) had symptomatic HF (mean age 58 ± 11 years, 62% male). HF with preserved ejection fraction (HF-pEF) was diagnosed in 43 (91%) patients, representing the dominant phenotype. Left ventricular mass index (LVMi) had the highest diagnostic utility (sensitivity 71% and specificity 83%) for HF diagnosis in FD, followed by E/e' > 9 (sensitivity 76% and specificity 78%) and global longitudinal strain (GLS) <16% (sensitivity 54% and specificity 88%). Log N-terminal pro-brain natriuretic peptide correlated significantly with LVMi (r = 0.60), E/e' (r = 0.54), and GLS (r = 0.52) (all Ps < 0.001) but not with left ventricular ejection fraction (r = -0.034, P = 0.72). During follow-up (mean 1208 ± 444 days), patients diagnosed with HF had a higher rate of all-cause mortality and worsening HF (33% vs. 1.5%, P < 0.001). Abnormal LVMi, E/e' > 9, and GLS < 16% were all associated with higher all-cause mortality and worsening HF. CONCLUSIONS: This study found a high prevalence of symptomatic HF in FD patients. HF-pEF was the dominant phenotype. LVMi, E/e', and GLS yielded the highest diagnostic utility for HF diagnosis and were significantly correlated with natriuretic peptides levels. Echocardiographic criteria proposed by current ESC HF guidelines apply to Fabry patients and predict cardiovascular events. At follow-up, Fabry patients with HF diagnosis had high event rates and significantly worse prognosis than patients without HF.

• Klíčová slova
• Echocardiography, Fabry disease, Global longitudinal strain, Heart failure, Left ventricular hypertrophy, Natriuretic peptides,
• MeSH
• Fabryho nemoc * komplikace   diagnóza   epidemiologie   MeSH
• funkce levé komory srdeční MeSH
• lidé středního věku MeSH
• lidé MeSH
• natriuretické peptidy MeSH
• senioři MeSH
• srdeční selhání * diagnóza   epidemiologie   etiologie   MeSH
• tepový objem MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• natriuretické peptidy MeSH

AIMS: Identification of heart failure (HF) patients with secondary mitral regurgitation (SMR) that benefit from mitral valve (MV) repair remains challenging. We have focused on the role of left ventricular global longitudinal strain (LV-GLS) and reservoir left atrial longitudinal strain (LASr) for the prediction of long-term survival and reverse remodelling in patients with SMR undergoing endoscopic MV repair. METHODS AND RESULTS: The study population consisted of 110 patients (age 67 ± 11 years, 66% men) with symptomatic SMR undergoing isolated MV repair using a minimally invasive surgical approach. Speckle tracking-derived LV-GLS and LASr were assessed in apical views using vendor-independent software. Over a median of 7.7 years (IQRs 2.9-11.2), 64 patients (58%) died. Significant reverse LV (↓ LVESVI >10 mL/m2 ), LA (↓ LAVI >10 mL/m2 ) remodelling or both were observed in 43 (39%), 37 (34%) and 19 (17%) patients, respectively. LV-GLS (HR 0.68, 95% CI 0.58-0.79, P < 0.001) and LASr (HR 0.93, 95% CI 0.88-0.97, P < 0.01) but not LV ejection fraction (LVEF) and LA volume index (LAVi) emerged as independent predictors of all-cause mortality in Cox regression analysis. LV-GLS was the only independent predictor of LV reverse remodelling (OR 1.24, 95% CI 1.05-1.43, P < 0.001) whereas LAVi and LASr were both independent predictors of LA reverse remodelling (both P < 0.05). In patients with atrial fibrillation at baseline, only LASr was an independent predictor (P < 0.05) of LA reverse remodelling. CONCLUSIONS: In patients with SMR undergoing endoscopic MV repair, LV-GLS and LASr are independently associated with long-term survival and reverse remodelling and may be helpful in selecting SMR patients who may benefit from this procedure.

• Klíčová slova
• Endoscopic mitral valve repair, Reverse remodelling, Secondary mitral regurgitation, Strain, Survival,
• MeSH
• funkce levé komory srdeční MeSH
• kardiochirurgické výkony * MeSH
• lidé středního věku MeSH
• lidé MeSH
• mitrální chlopeň diagnostické zobrazování   chirurgie   MeSH
• mitrální insuficience * diagnóza   chirurgie   MeSH
• senioři MeSH
• tepový objem MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

INTRODUCTION: Phosphodiesterase-5a inhibition (PDE5i) leads to favorable changes in pulmonary hemodynamic and cardiac output (CO) in patients with advanced heart failure (HF) and reduced ejection fraction (HFrEF). The hemodynamic response to PDE5i could be heterogeneous and the clinical variables associated with these changes are scarcely investigated. MATERIALS AND METHODS: Of 260 patients with advanced HFrEF referred for advanced therapies [cardiac transplant/left ventricular assist device (LVAD)], 55 had pulmonary hypertension (PH) and fulfilled the criteria for the PDE5i vasoreactivity test. Right heart catheterization (RHC) was performed as a part of clinical evaluation before and after 20-mg intravenous sildenafil. Absolute and relative changes in pulmonary vascular resistance (PVR) were evaluated to assess hemodynamic response to PDE5i. Clinical, biochemical, and hemodynamic factors associated with PVR changes were identified. RESULTS: Sildenafil administration reduced PVR (- 45.3%) and transpulmonary gradient (TPG; - 34.8%) and increased CO (+ 13.6%). Relative change analysis showed a negative moderate association between baseline plasma potassium and changes in PVR (r = - 0.48; p = 0.001) and TPG (r = - 0.43; p = 0.005) after PDE5i. Aldosterone concentration shows a direct moderate association with PVR changes after PDE5i. A significant moderate association was also demonstrated between CO improvement and the severity of mitral (r = 0.42; p = 0.002) and tricuspid (r = 0.39; p = 0.004) regurgitation. CONCLUSION: We identified plasma potassium, plasma aldosterone level, and atrioventricular valve regurgitations as potential cofounders of hemodynamic response to acute administration of PDE5i. Whether modulation of potassium levels could enhance pulmonary vasoreactivity in advanced HFrEF deserves further research.

• Klíčová slova
• heart failure, phospodiesterase inhibitors, potassium, pulmonary hypertension, pulmonary vascular resistance,
• Publikační typ
• časopisecké články MeSH

Patients with chronic kidney disease (CKD) have an increased risk of premature mortality, mainly due to cardiovascular causes. The association between hemodialysis and accelerated atherosclerosis has long been described. The ankle-brachial index (ABI) is a surrogate marker of atherosclerosis and recent studies indicate its utility as a predictor of future cardiovascular disease and all-cause mortality. The clinical implications of ABI cut-points are not well defined in patients with CKD. Echocardiography is the most widely used imaging method for cardiac evaluation. Structural and functional myocardial abnormalities are common in patients with CKD due to pressure and volume overload as well as non-hemodynamic factors associated with CKD. Our study aimed to identify markers of subclinical cardiovascular risk assessed using ABI and 2D and 3D echocardiographic parameters evaluating left ventricular (LV) structure and function in patients with end-stage renal disease (ESRD) (patients undergoing dialysis), patients after kidney transplantation and non-ESRD patients (control). In ESRD, particularly in hemodialysis patients, changes in cardiac structure, rather than function, seems to be more pronounced. 3D echocardiography appears to be more sensitive than 2D echocardiography in the assessment of myocardial structure and function in CKD patients. Particularly 3D derived end-diastolic volume and 3D derived LV mass indexed for body surface appears to deteriorate in dialyzed and transplanted patients. In 2D echocardiography, myocardial mass represented by left ventricular mass/body surface area index (LVMI) appears to be a more sensitive marker of cardiac structural changes, compared to relative wall thickness (RWT), left ventricle and diastolic diameter index (LVEDDI) and left atrial volume index (LAVI). We observed a generally favorable impact of kidney transplantation on cardiac structure and function; however, the differences were non-significant. The improvement seems to be more pronounced in cardiac function parameters, peak early diastolic velocity/average peak early diastolic velocity of mitral valve annulus (E/e´), 3D left ventricle ejection fraction (LV EF) and global longitudinal strain (GLS). We conclude that ABI is not an appropriate screening test to determine the cardiovascular risk in patients with ESRD.

• MeSH
• chronické selhání ledvin diagnostické zobrazování   patofyziologie   MeSH
• dospělí MeSH
• echokardiografie trojrozměrná * MeSH
• funkce levé komory srdeční MeSH
• hodnocení rizik MeSH
• lidé středního věku MeSH
• lidé MeSH
• průřezové studie MeSH
• rizikové faktory kardiovaskulárních chorob MeSH
• srdeční komory diagnostické zobrazování   MeSH
• studie případů a kontrol MeSH
• tlakový index kotník-paže MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH