In this systematic review, we report on the effects of diuretic deprescribing compared to continued diuretic use. We included clinical studies reporting on outcomes such as mortality, heart failure recurrence, tolerability and feasibility. We assessed risk of bias and certainty of the evidence using the GRADE framework. We included 25 publications from 22 primary studies (15 randomized controlled trials; 7 nonrandomized studies). The mean number of participants in the deprescribing groups was 35, and median/mean age 64 years. In patients with heart failure, there was no clear evidence that diuretic deprescribing was associated with increased mortality compared to diuretic continuation (low certainty evidence). The risk of cardiovascular composite outcomes associated with diuretic deprescribing was inconsistent (studies showing lower risk for diuretic deprescribing, or comparable risk with diuretic continuation; very low certainty evidence). The effect on heart failure recurrence after diuretic deprescribing in patients with diuretics for heart failure, and of hypertension in patients with diuretics for hypertension was inconsistent across the included studies (low certainty evidence). In patients with diuretics for hypertension, diuretic deprescribing was well tolerated (moderate certainty evidence), while in patients with diuretics for heart failure, deprescribing diuretics can result in complaints of peripheral oedema (very low certainty evidence). The overall risk of bias was generally high. In summary, this systematic review suggests that diuretic discontinuation could be a safe and feasible treatment option for carefully selected patients. However, there isa lack of high-quality evidence on its feasibility, safety and tolerability of diuretic deprescribing, warranting further research.

• MeSH
• depreskripce * MeSH
• diuretika * škodlivé účinky   aplikace a dávkování   terapeutické užití   MeSH
• dospělí MeSH
• hypertenze farmakoterapie   MeSH
• lidé MeSH
• medicína založená na důkazech MeSH
• randomizované kontrolované studie jako téma MeSH
• směrnice pro lékařskou praxi jako téma MeSH
• srdeční selhání * farmakoterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• systematický přehled MeSH

INTRODUCTION: We aimed to evaluate the prognostic impact of renal insufficiency and fluctuation of glomerular filtration observed during hospitalization for heart failure (HF). METHODS: We followed 3,639 patients hospitalized for acute HF and assessed the mortality risk associated with moderate or severe renal insufficiency, either permanent or transient. RESULTS: After adjustment, severe renal failure defined as estimated glomerular filtration (eGFR) <30 mL/min indicates ≈60% increase in 5-year mortality risk. Similar risk also had patients with only transient decline of eGFR to this range. In contrast, we did not observe any apparent mortality risk attributable to mild/moderate renal insufficiency (eGFR 30-59.9 mL/min), regardless of whether it was transient or permanent. CONCLUSION: Even transient severe renal failure during hospitalization indicates poor long-term prognosis of patients with manifested HF. In contrast, only moderate renal insufficiency observed during hospitalization has no additive long-term mortality impact.

• MeSH
• hodnoty glomerulární filtrace MeSH
• hospitalizace MeSH
• ledviny MeSH
• lidé MeSH
• prognóza MeSH
• renální insuficience * komplikace   MeSH
• srdeční selhání * komplikace   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Aminophylline, a bronchodilator mainly used to treat severe asthma attacks, may induce arrhythmias. Unfortunately, the underlying mechanism is not well understood. We have recently described a significant, on average inhibitory effect of aminophylline on inward rectifier potassium current IK1, known to substantially contribute to arrhythmogenesis, in rat ventricular myocytes at room temperature. This study was aimed to examine whether a similar effect may be observed under clinically relevant conditions. Experiments were performed using the whole cell patch clamp technique at 37°C on enzymatically isolated healthy porcine and failing human ventricular myocytes. The effect of clinically relevant concentrations of aminophylline (10-100 μM) on IK1 did not significantly differ in healthy porcine and failing human ventricular myocytes. IK1 was reversibly inhibited by ∼20 and 30 % in the presence of 30 and 100 μM aminophylline, respectively, at -110 mV; an analogical effect was observed at -50 mV. To separate the impact of IK1 changes on AP configuration, potentially interfering ionic currents were blocked (L-type calcium and delayed rectifier potassium currents). A significant prolongation of AP duration was observed in the presence of 100 μM aminophylline in porcine cardiomyocytes which well agreed with the effect of a specific IK1 inhibitor Ba2+ (10 μM) and with the result of simulations using a porcine ventricular cell model. We conclude that the observed effect of aminophylline on healthy porcine and failing human IK1 might be involved in its proarrhythmic action. To fully understand the underlying mechanism, potential aminophylline impact on other ionic currents should be explored.

• MeSH
• akční potenciály účinky léků   MeSH
• aminofylin * farmakologie   MeSH
• draslíkové kanály dovnitř usměrňující * metabolismus   MeSH
• kardiomyocyty * účinky léků   metabolismus   MeSH
• lidé MeSH
• metoda terčíkového zámku MeSH
• prasata MeSH
• srdeční komory účinky léků   metabolismus   MeSH
• srdeční selhání metabolismus   farmakoterapie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Empagliflozín je inhibítor sodíkovo-glukózového kotransportéra 2 (SGLT2i – Sodium-GLucose co-Transporter 2 inhibitor) primárne vyvinutý ako perorálne antidiabetikum. Postupne pribudli dôkazy z veľkých randomizovaných klinických štúdií pre multiorgánové benefity empagliflozínu výrazne presahujúce jeho glykémiu znižujúci efekt. V súčasnosti tak máme okrem diabetologickej indikácie aj indikáciu na terapiu srdcového zlyhávania a chronickej obličkovej choroby bez ohľadu na prítomnosť diagnózy diabetu. Tieto skutočnosti zapadajú do konceptu novokoncipovaného kardio-reno-metabolického (CRM – Cardio-Renal-Metabolic) syndrómu, ktorého včasné terapeutické ovplyvnenie práve liekmi ako empagliflozín má významné pozitívne efekty na zdravie celej populácie. V článku sú diskutované relevantné klinické štúdie a dáta z reálnej praxe (RWE – Real World Evidence) pre multiorgánové efekty a indikácie empagliflozínu a ich význam pre klinickú prax.

Empagliflozin is a sodium-glucose co-transporter 2 inhibitor (SGLT2i) primarily developed as an oral antidiabetic drug. Later on, evidence from large randomized controlled trials showed that empagliflozin has multiorgan benefits far exceeding its glucose lowering effects. At present empagliflozin has antidiabetic, cardiac and renal indications whereby the last two mentioned are independent on the presence of the diagnosis of diabetes. These data thus fit into the newly formulated concept of cardio-renal-metabolic (CRM) syndrome (or CKM – cardiovascular-kidney-metabolic syndrome). Targeted and early therapeutic intervention against CRM syndrome, with medications like empagliflozin, has profound positive effects on the health outcomes of the whole population. This article reviews the relevant clinical studies and real world evidence (RWE) data and their impact on clinical practice.

• Klíčová slova
• empagliflozin,
• MeSH
• benzhydrylové sloučeniny MeSH
• chronická renální insuficience diagnóza   farmakoterapie   MeSH
• diabetes mellitus farmakoterapie   MeSH
• glifloziny * aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• glukosidy MeSH
• kardiorenální syndrom farmakoterapie   MeSH
• kardiovaskulární nemoci farmakoterapie   prevence a kontrola   MeSH
• lidé MeSH
• metabolický syndrom farmakoterapie   komplikace   MeSH
• nádory prevence a kontrola   MeSH
• srdeční selhání farmakoterapie   MeSH
• urolitiáza prevence a kontrola   MeSH
• Check Tag
• lidé MeSH

Patients with obstructive hypertrophic cardiomyopathy (oHCM) have increased risk of arrhythmia, stroke, heart failure, and sudden death. Contemporary management of oHCM has decreased annual hospitalization and mortality rates, yet patients have worsening health-related quality of life due to impaired exercise capacity and persistent residual symptoms. Here we consider the design of clinical trials evaluating potential oHCM therapies in the context of SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM). This large, phase 3 trial is now fully enrolled (N = 282). Baseline characteristics reflect an ethnically diverse population with characteristics typical of patients encountered clinically with substantial functional and symptom burden. The study will assess the effect of aficamten vs placebo, in addition to standard-of-care medications, on functional capacity and symptoms over 24 weeks. Future clinical trials could model the approach in SEQUOIA-HCM to evaluate the effect of potential therapies on the burden of oHCM. (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM [SEQUOIA-HCM]; NCT05186818).

• MeSH
• hypertrofická kardiomyopatie * komplikace   MeSH
• kvalita života MeSH
• lidé MeSH
• sekvoj * MeSH
• srdeční selhání * farmakoterapie   MeSH
• tolerance zátěže MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

AIMS: Heart failure-related cardiogenic shock (HF-CS) accounts for a significant proportion of CS cases. Whether patients with de novo HF and those with acute-on-chronic HF in CS differ in clinical characteristics and outcome remains unclear. The aim of this study was to evaluate differences in clinical presentation and mortality between patients with de novo and acute-on-chronic HF-CS. METHODS AND RESULTS: In this international observational study, patients with HF-CS from 16 tertiary care centres in five countries were enrolled between 2010 and 2021. To investigate differences in clinical presentation and 30-day mortality, adjusted logistic/Cox regression models were fitted. Patients (n = 1030) with HF-CS were analysed, of whom 486 (47.2%) presented with de novo HF-CS and 544 (52.8%) with acute-on-chronic HF-CS. Traditional markers of CS severity (e.g. blood pressure, heart rate and lactate) as well as use of treatments were comparable between groups. However, patients with acute-on-chronic HF-CS were more likely to have a higher CS severity and also a higher mortality risk, after adjusting for relevant confounders (de novo HF 45.5%, acute-on-chronic HF 55.9%, adjusted hazard ratio 1.38, 95% confidence interval 1.10-1.72, p = 0.005). CONCLUSION: In this large HF-CS cohort, acute-on-chronic HF-CS was associated with more severe CS and higher mortality risk compared to de novo HF-CS, although traditional markers of CS severity and use of treatments were comparable. These findings highlight the vast heterogeneity of patients with HF-CS, emphasize that HF chronicity is a relevant disease modifier in CS, and indicate that future clinical trials should account for this.

• MeSH
• kardiogenní šok * etiologie   MeSH
• lidé MeSH
• mortalita v nemocnicích MeSH
• prognóza MeSH
• srdeční selhání * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH

Pacienti s chronickým onemocněním ledvin, zejména starší osoby, jsou v nepřiměřeně vysokém riziku kardiovaskulárních komplikací a úmrtí. Patofyziologické a klinické souvislosti mezi ledvinami a kardiovaskulárním systémem jsou výstižně shrnuty v terminologii kardiorenálních syndromů. Chronický renokardiální syndrom (kardiorenální syndrom typ 4) je společným důsledkem známých tradičních, ale také tzv. netradičních rizikových faktorů vyplývajících z poškození renální tkáně a renální funkce. Chronické onemocnění ledvin samo o sobě představuje nezávislý rizikový kardiovaskulární faktor. Článek upozorňuje na vysokou mortalitu pacientů s chronickými nemocemi ledvin, a to již od časných funkčních stadií chronického onemocnění ledvin, a připomíná základní patogenezi a klinický význam nejdůležitějších renálně podmíněných netradičních kardiovaskulárních rizik, včetně těch, která jsou důležitá zejména pro pacienty vysokého věku. Korespondenční adresa: prof. MUDr. Sylvie Dusilová Sulková, DrSc. Nefrologická klinika, LF UK a FN Sokolská 581 500 05 Hradec Králové e-mail: sylvie.dusilova@fnhk.cz

Patients with chronic kidney disease, especially the elderly, are at disproportionately high risk of cardiovascular complications and death. The pathophysiological and clinical links between the kidney and the cardiovascular system are aptly summarized in the terminology of cardiorenal syndromes. Chronic renal syndrome (cardiorenal syndrome type 4) is a common consequence of known traditional but also so-called non-traditional risk factors resulting from renal tissue damage and renal function. Chronic kidney disease itself is an independent cardiovascular risk factor. The article highlights the high mortality rate of patients with chronic kidney disease, starting from the early functional stages of chronic kidney disease, and recalls the basic pathogenesis and clinical significance of the most important renal-related nontraditional cardiovascular risks, including those that are particularly important for elderly patients.

• MeSH
• chronická renální insuficience * komplikace   patofyziologie   MeSH
• extracelulární tekutina fyziologie   MeSH
• fibroblastový růstový faktor 23 MeSH
• kardiorenální syndrom * klasifikace   komplikace   patofyziologie   prevence a kontrola   MeSH
• lidé MeSH
• rizikové faktory kardiovaskulárních chorob MeSH
• senioři MeSH
• uremické toxiny fyziologie   MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

BACKGROUND: Physical activity is pivotal in managing heart failure with reduced ejection fraction, and walking integrated into daily life is an especially suitable form of physical activity. This study aimed to determine whether a 6-month lifestyle walking intervention combining self-monitoring and regular telephone counseling improves functional capacity assessed by the 6-minute walk test (6MWT) in patients with stable heart failure with reduced ejection fraction compared with usual care. METHODS: The WATCHFUL trial (Pedometer-Based Walking Intervention in Patients With Chronic Heart Failure With Reduced Ejection Fraction) was a 6-month multicenter, parallel-group randomized controlled trial recruiting patients with heart failure with reduced ejection fraction from 6 cardiovascular centers in the Czech Republic. Eligible participants were ≥18 years of age, had left ventricular ejection fraction <40%, and had New York Heart Association class II or III symptoms on guidelines-recommended medication. Individuals exceeding 450 meters on the baseline 6MWT were excluded. Patients in the intervention group were equipped with a Garmin vívofit activity tracker and received monthly telephone counseling from research nurses who encouraged them to use behavior change techniques such as self-monitoring, goal-setting, and action planning to increase their daily step count. The patients in the control group continued usual care. The primary outcome was the between-group difference in the distance walked during the 6MWT at 6 months. Secondary outcomes included daily step count and minutes of moderate to vigorous physical activity as measured by the hip-worn Actigraph wGT3X-BT accelerometer, NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity C-reactive protein biomarkers, ejection fraction, anthropometric measures, depression score, self-efficacy, quality of life, and survival risk score. The primary analysis was conducted by intention to treat. RESULTS: Of 218 screened patients, 202 were randomized (mean age, 65 years; 22.8% female; 90.6% New York Heart Association class II; median left ventricular ejection fraction, 32.5%; median 6MWT, 385 meters; average 5071 steps/day; average 10.9 minutes of moderate to vigorous physical activity per day). At 6 months, no between-group differences were detected in the 6MWT (mean 7.4 meters [95% CI, -8.0 to 22.7]; P=0.345, n=186). The intervention group increased their average daily step count by 1420 (95% CI, 749 to 2091) and daily minutes of moderate to vigorous physical activity by 8.2 (95% CI, 3.0 to 13.3) over the control group. No between-group differences were detected for any other secondary outcomes. CONCLUSIONS: Whereas the lifestyle intervention in patients with heart failure with reduced ejection fraction improved daily steps by about 25%, it failed to demonstrate a corresponding improvement in functional capacity. Further research is needed to understand the lack of association between increased physical activity and functional outcomes. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03041610.

• MeSH
• chůze MeSH
• dysfunkce levé srdeční komory * MeSH
• funkce levé komory srdeční MeSH
• kvalita života MeSH
• lidé MeSH
• senioři MeSH
• srdeční selhání * terapie   farmakoterapie   MeSH
• tepový objem MeSH
• životní styl MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: Patients with heart failure (HF) with preserved ejection fraction (HFpEF) and obesity experience a high burden of symptoms and functional impairment, and a poor quality of life. In the STEP-HFpEF trial (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity), once-weekly semaglutide 2.4 mg improved symptoms, physical limitations, and exercise function, and reduced inflammation and body weight. This prespecified analysis investigated the effects of semaglutide on the primary and confirmatory secondary end points across the range of the Kansas City Cardiomyopathy Questionnaire (KCCQ) scores at baseline and on all key summary and individual KCCQ domains. METHODS: STEP-HFpEF randomly assigned 529 participants with symptomatic HF, an ejection fraction of ≥45%, and a body mass index of ≥30 kg/m2 to once-weekly semaglutide 2.4 mg or placebo for 52 weeks. Dual primary end points change in KCCQ-Clinical Summary Score (CSS) and body weight. Confirmatory secondary end points included change in 6-minute walk distance, a hierarchical composite end point (death, HF events, and change in KCCQ-CSS and 6-minute walk distance) and change in C-reactive protein. Patients were stratified by KCCQ-CSS tertiles at baseline. Semaglutide effects on the primary, confirmatory secondary, and select exploratory end points (N-terminal pro-brain natriuretic peptide) were examined across these subgroups. Semaglutide effects on additional KCCQ domains (Total Symptom Score [including symptom burden and frequency], Physical Limitations Score, Social Limitations Score, Quality of Life Score, and Overall Summary Score) were also evaluated. RESULTS: Baseline median KCCQ-CSS across tertiles was 37, 59, and 77 points, respectively. Semaglutide consistently improved primary end points across KCCQ tertiles 1 to 3 (estimated treatment differences [95% CI]: for KCCQ-CSS, 10.7 [5.4 to 16.1], 8.1 [2.7 to 13.4], and 4.6 [-0.6 to 9.9] points; for body weight, -11 [-13.2 to -8.8], -9.4 [-11.5 to -7.2], and -11.8 [-14.0 to -9.6], respectively; Pinteraction=0.28 and 0.29, respectively); the same was observed for confirmatory secondary and exploratory end points (Pinteraction>0.1 for all). Semaglutide-treated patients experienced improvements in all key KCCQ domains (estimated treatment differences, 6.7-9.6 points across domains; P≤0.001 for all). Greater proportion of semaglutide-treated versus placebo-treated patients experienced at least 5-, 10-, 15-, and 20-point improvements in all KCCQ domains (odds ratios, 1.6-2.9 across domains; P<0.05 for all). CONCLUSIONS: In patients with HFpEF and obesity, semaglutide produced large improvements in HF-related symptoms, physical limitations, exercise function, inflammation, body weight, and N-terminal pro-brain natriuretic peptide, regardless of baseline health status. The benefits of semaglutide extended to all key KCCQ domains. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04788511.

• MeSH
• glukagonu podobné peptidy * MeSH
• kvalita života * MeSH
• lidé MeSH
• natriuretický peptid typu B MeSH
• obezita farmakoterapie   MeSH
• srdeční selhání * diagnóza   farmakoterapie   MeSH
• tepový objem MeSH
• zánět MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

BACKGROUND: Left bundle branch area pacing (LBBAP) may be associated with greater improvement in left ventricular ejection fraction and reduction in death or heart failure hospitalization compared with biventricular pacing (BVP) in patients requiring cardiac resynchronization therapy. We sought to compare the occurrence of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) and new-onset atrial fibrillation (AF) in patients undergoing BVP and LBBAP. METHODS: The I-CLAS study (International Collaborative LBBAP Study) included patients with left ventricular ejection fraction ≤35% who underwent BVP or LBBAP for cardiac resynchronization therapy between January 2018 and June 2022 at 15 centers. We performed propensity score-matched analysis of LBBAP and BVP in a 1:1 ratio. We assessed the incidence of VT/VF and new-onset AF among patients with no history of AF. Time to sustained VT/VF and time to new-onset AF was analyzed using the Cox proportional hazards survival model. RESULTS: Among 1778 patients undergoing cardiac resynchronization therapy (BVP, 981; LBBAP, 797), there were 1414 propensity score-matched patients (propensity score-matched BVP, 707; propensity score-matched LBBAP, 707). The occurrence of VT/VF was significantly lower with LBBAP compared with BVP (4.2% versus 9.3%; hazard ratio, 0.46 [95% CI, 0.29-0.74]; P<0.001). The incidence of VT storm (>3 episodes in 24 hours) was also significantly lower with LBBAP compared with BVP (0.8% versus 2.5%; P=0.013). Among 299 patients with cardiac resynchronization therapy pacemakers (BVP, 111; LBBAP, 188), VT/VF occurred in 8 patients in the BVP group versus none in the LBBAP group (7.2% versus 0%; P<0.001). In 1194 patients with no history of VT/VF or antiarrhythmic therapy (BVP, 591; LBBAP, 603), the occurrence of VT/VF was significantly lower with LBBAP than with BVP (3.2% versus 7.3%; hazard ratio, 0.46 [95% CI, 0.26-0.81]; P=0.007). Among patients with no history of AF (n=890), the occurrence of new-onset AF >30 s was significantly lower with LBBAP than with BVP (2.8% versus 6.6%; hazard ratio, 0.34 [95% CI, 0.16-0.73]; P=0.008). The incidence of AF lasting >24 hours was also significantly lower with LBBAP than with BVP (0.7% versus 2.9%; P=0.015). CONCLUSIONS: LBBAP was associated with a lower incidence of sustained VT/VF and new-onset AF compared with BVP. This difference remained significant after adjustment for differences in baseline characteristics between patients with BVP and LBBAP. Physiological resynchronization by LBBAP may be associated with lower risk of arrhythmias compared with BVP.

• MeSH
• elektrokardiografie MeSH
• fibrilace komor epidemiologie   etiologie   terapie   MeSH
• funkce levé komory srdeční MeSH
• komorová tachykardie * epidemiologie   etiologie   terapie   MeSH
• lidé MeSH
• srdeční resynchronizační terapie * škodlivé účinky   MeSH
• srdeční selhání * epidemiologie   terapie   MeSH
• tepový objem MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH