IMPORTANCE: Impaired exercise capacity is a cardinal manifestation of obstructive hypertrophic cardiomyopathy (HCM). The Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic Obstructive HCM (SEQUOIA-HCM) is a pivotal study characterizing the treatment effect of aficamten, a next-in-class cardiac myosin inhibitor, on a comprehensive set of exercise performance and clinical measures. OBJECTIVE: To evaluate the effect of aficamten on exercise performance using cardiopulmonary exercise testing with a novel integrated measure of maximal and submaximal exercise performance and evaluate other exercise measures and clinical correlates. DESIGN, SETTING, AND PARTICIPANTS: This was a prespecified analysis from SEQUOIA-HCM, a double-blind, placebo-controlled, randomized clinical trial. Patients were recruited from 101 sites in 14 countries (North America, Europe, Israel, and China). Individuals with symptomatic obstructive HCM with objective exertional intolerance (peak oxygen uptake [pVO2] ≤90% predicted) were included in the analysis. Data were analyzed from January to March 2024. INTERVENTIONS: Randomized 1:1 to aficamten (5-20 mg daily) or matching placebo for 24 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome was change from baseline to week 24 in integrated exercise performance, defined as the 2-component z score of pVO2 and ventilatory efficiency throughout exercise (minute ventilation [VE]/carbon dioxide output [VCO2] slope). Response rates for achieving clinically meaningful thresholds for change in pVO2 and correlations with clinical measures of treatment effect (health status, echocardiographic/cardiac biomarkers) were also assessed. RESULTS: Among 282 randomized patients (mean [SD] age, 59.1 [12.9] years; 115 female [40.8%], 167 male [59.2%]), 263 (93.3%) had core laboratory-validated exercise testing at baseline and week 24. Integrated composite exercise performance improved in the aficamten group (mean [SD] z score, 0.17 [0.51]) from baseline to week 24, whereas the placebo group deteriorated (mean [SD] z score, -0.19 [0.45]), yielding a placebo-corrected improvement of 0.35 (95% CI, 0.25-0.46; P <.001). Further, aficamten treatment demonstrated significant improvements in total workload, circulatory power, exercise duration, heart rate reserve, peak heart rate, ventilatory efficiency, ventilatory power, and anaerobic threshold (all P <.001). In the aficamten group, large improvements (≥3.0 mL/kg per minute) in pVO2 were more common than large reductions (32% and 2%, respectively) compared with placebo (16% and 11%, respectively). Improvements in both components of the primary outcome, pVO2 and VE/VCO2 slope throughout exercise, were significantly correlated with improvements in symptom burden and hemodynamics (all P <.05). CONCLUSIONS AND RELEVANCE: This prespecified analysis of the SEQUOIA-HCM randomized clinical trial found that aficamten treatment improved a broad range of exercise performance measures. These findings offer valuable insight into the therapeutic effects of aficamten. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05186818.
- MeSH
- dvojitá slepá metoda MeSH
- hypertrofická kardiomyopatie * patofyziologie farmakoterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- spotřeba kyslíku fyziologie MeSH
- srdeční myosiny MeSH
- tolerance zátěže * fyziologie MeSH
- zátěžový test * metody MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
This study aims to explore: (1) the validity of post-exercise ultra-short-term heart rate variability (HRVust) after two different bouts of repeated sprint ability test (RSA), and (2) the relationship between HRVust measure and RSA performance. Twenty adolescent male futsal players voluntarily participated in this study (age: 17.65 ± 1.81 years, body height: 170.88 ± 4.98 cm, body weight: 61.78 ± 4.67 kg). The participants performed a standard RSA test (RSAstandard) and an RSA test with a 10% decrement of the best sprint time test (RSA10%decrement) on two separate occasions within a week. On both occasions, a 5-min resting electrocardiography was administered pre- and post-RSA exercise protocols. The first 30-s (HRVust30s), 60-s (HRVust60s), and 60-120-s (HRVust1-2min) were extracted and used to compare with the standard of 5-min HRV recording (HRVcriterion). The natural logarithm (ln) of the standard deviation of normal-to-normal intervals (SDNN) and root mean square of successive normal-to-normal interval differences (RMSSD) HRV indices were utilised to establish intraclass correlation coefficient (ICC2,1), coefficient of variation (%CV), and Pearson product-moment correlation (r). Results revealed the ICC values of HRVust lnSDNN (RSAstandard = 0.77-0.88; RSA10%decrement = 0.41-0.71) and lnRMSSD (RSAstandard = 0.81-0.86; RSA10%decrement = 0.57-0.82). Furthermore, significantly positive correlations between best sprint time and post-exercise HRVust indices were found in lnSDNN (r = 0.47-0.62; p < 0.05) and lnRMSSD (r = 0.45; p < 0.05). Additionally, a large CV of lnSDNN (RSAstandard = 32%-45%; RSA10%decrement = 29%-39%), lnRMSSD (RSAstandard = 50%-66%; RSA10%decrement = 48%-52%), and ratio (RSAstandard = 45%-126%; RSA10%decrement = 27%-45%) was found after the RSA protocols. In conclusion, the number of bouts of RSA exercise potentially influences the agreement of post-exercise time-domain HRVust indices to standard HRV measure.
- MeSH
- běh * fyziologie MeSH
- cvičení fyziologie MeSH
- elektrokardiografie MeSH
- lidé MeSH
- mladiství MeSH
- sportovní výkon fyziologie MeSH
- srdeční frekvence * fyziologie MeSH
- zátěžový test * metody MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- lidé MeSH
- nemoci srdce MeSH
- test na nakloněné rovině metody MeSH
- zátěžový test * metody MeSH
- Check Tag
- lidé MeSH
Z hlediska veřejného zdraví představuje prediabetes jeden z hlavních rizikových faktorů pro rozvoj diabetu 2. typu. Index obnovy srdeční frekvence (heart rate recovery index, HRRI) je nezávislým ukazatelem autonomních funkcí a prediktorem rozvoje kardiovaskulárních onemocnění (KVO). Cílem našeho výzkumu bylo stanovit hodnotu HRRI u jedinců s prediabetem. Metody: Do studie bylo zařazeno 400 pacientů navštěvujících kliniku kardiologie: 164 (41 %) žen a 316 (59 %) mužů. Podle Bruceho protokolu museli všichni účastníci absolvovat zátěžové EKG vyšetření na běžeckém pásu. Průběh obnovy srdeční frekvence se zaznamenává 1, 2, 3 a 5 minut po zátěžovém testu, přičemž se odečítá maximální srdeční frekvence jedince na konci testu od hodnoty naměřené během 1, 2, 3 a 5 minut zotavování. Výsledky: Obě skupiny měly podobné hodnoty délky zátěže, metabolického ekvivalentu (metabolic equivalent of task, MET), maximální srdeční frekvenci i vstupní a maximální hodnoty systolického a diastolického krevního tlaku i změny těchto dvou parametrů (p > 0,05). Hodnoty HRRI po 1, 2, 3 a 5 minutách byly vyšší u pacientů, kteří prodělali onemocnění covid-19 (p < 0,001). Závěry: Prediabetes má statisticky významný vliv na hodnotu HRRI. Prediabetes může působit na nervový i kardiovaskulární systém.
Background: Prediabetes is a major public health risk factor for type 2 diabetes. The heart rate recovery index (HRRI) shows autonomic function and predicts cardiovascular disease (CVD) independently. The objective of the research was to assess the HRRI in individuals with prediabetes. Methods: The study comprised 400 cardiology clinic patients, 164 (41% female) and 316 (59% male). The Bruce protocol required treadmill stress ECGs for all patients. After the stress test, HRRIs were collected at 1, 2, 3, and 5 minutes. HRRI is calculated by subtracting the subject's maximal exercise HR at the end of the session from HR after 1, 2, 3, and 5 minutes of recovery. Results: Both groups had a similar exercise time, METs, max. HR, baseline, max., and change in SBP and DBP (p >0.05). HRRIs were higher in COVID-19 patients than controls at 1, 2, 3, and 5 minutes (p <0.001). Conclusions: Prediabetes has a significant influence on the HRRI. Prediabetes has the potential to impact neural-cardiovascular systems.
- Klíčová slova
- Index obnovy srdeční frekvence,
- MeSH
- elektrokardiografie metody MeSH
- kardiovaskulární nemoci * etiologie prevence a kontrola MeSH
- klinická studie jako téma metody MeSH
- lidé MeSH
- nemoci autonomního nervového systému etiologie patofyziologie MeSH
- prediabetes * komplikace patofyziologie MeSH
- srdeční frekvence * MeSH
- zátěžový test metody MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
Traditionally, aborted cardiac arrest (ACA) due to documented ventricular fibrillation (VF) in the absence of structural heart disease has been termed idiopathic VF. By careful evaluation, a specific etiology can be found in a substantial proportion of patients. The aim of this survey was to assess the yield of an advanced diagnostic work-up to reveal a causative etiology in a real-life clinical setting. Patients from the University Hospital Brno's ACA database were analyzed (514 patients in total). Forty-six patients (31 males) fulfilled the inclusion criteria, which were: (1) absence of structural pathology on echocardiography; (2) absence of coronary artery disease; and (3) absence of reversible cause of ACA. The diagnostic work-up consisted in cardiac magnetic resonance imaging, stress testing, sodium channel blocker challenge, and genetic testing according to the availability of the method and patient compliance. A specific disease was found in 17 individuals (37.0%), although at least one diagnostic step was refused by 13 patients (28.3%). True idiopathic VF was confirmed in 7 patients (15.2%), for whom the entire diagnostic work-up did not reveal any specific pathology. Our real-life survey shows that, even with an incomplete diagnostic work-up (due to the unavailability of a particular method or variable patient compliance), a specific diagnosis can be identified in more than one third of the cases of "idiopathic" VF, which can thus enable targeted treatment and family screening.
- MeSH
- dospělí MeSH
- echokardiografie MeSH
- fibrilace komor * diagnóza MeSH
- genetické testování metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- senioři MeSH
- zátěžový test MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Physical activity is a crucial demand on cystic fibrosis treatment management. The highest value of oxygen uptake (VO2peak) is an appropriate tool to evaluate the physical activity in these patients. However, there are several other valuable CPET parameters describing exercise tolerance (Wpeak, VO2VT1, VO2VT2, VO2/HRpeak, etc.), and helping to better understand the effect of specific treatment (VE, VT, VD/VT etc.). Limited data showed ambiguous results of this improvement after CFTR modulator treatment. Elexacaftor/tezacaftor/ivacaftor medication improves pulmonary function and quality of life, whereas its effect on CPET has yet to be sufficiently demonstrated. METHODS: We performed a single group prospective observational study of 10 adolescent patients with cystic fibrosis who completed two CPET measurements between January 2019 and February 2023. During this period, elexacaftor/tezacaftor/ivacaftor treatment was initiated in all of them. The first CPET at the baseline was followed by controlled CPET at least one year after medication commencement. We focused on interpreting the data on their influence by the novel therapy. We hypothesized improvements in cardiorespiratory fitness following treatment. We applied the Wilcoxon signed-rank test. The data were adjusted for age at the time of CPET to eliminate bias of aging in adolescent patients. RESULTS: We observed significant improvement in peak workload, VO2 peak, VO2VT1, VO2VT2, VE/VCO2 slope, VE, VT, RQ, VO2/HR peak and RR peak. The mean change in VO2 peak was 5.7 mL/kg/min, or 15.9% of the reference value (SD ± 16.6; p= 0.014). VO2VT1 improved by 15% of the reference value (SD ± 0.1; p= 0.014), VO2VT2 improved by 0.5 (SD ± 0.4; p= 0.01). There were no differences in other parameters. CONCLUSION: Exercise tolerance improved after elexacaftor/tezacaftor/ivacaftor treatment initiation. We suggest that the CFTR modulator alone is not enough for recovering physical decondition, but should be supplemented with physical activity and respiratory physiotherapy. Further studies are needed to examine the effect of CFTR modulators and physical therapy on cardiopulmonary exercise tolerance.
- MeSH
- aminofenoly * terapeutické užití MeSH
- benzodioxoly * terapeutické užití MeSH
- chinolony * terapeutické užití MeSH
- cystická fibróza * farmakoterapie patofyziologie MeSH
- dítě MeSH
- fixní kombinace léků * MeSH
- indoly * terapeutické užití MeSH
- kardiorespirační zdatnost MeSH
- lidé MeSH
- mladiství MeSH
- pilotní projekty MeSH
- prospektivní studie MeSH
- pyrazoly * terapeutické užití MeSH
- pyridiny * terapeutické užití MeSH
- pyrrolidiny MeSH
- pyrroly terapeutické užití MeSH
- spotřeba kyslíku MeSH
- tolerance zátěže účinky léků MeSH
- zátěžový test MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
BACKGROUND: One of the major determinants of exercise intolerance and limiting symptoms among patients with obstructive hypertrophic cardiomyopathy (HCM) is an elevated intracardiac pressure resulting from left ventricular outflow tract obstruction. Aficamten is an oral selective cardiac myosin inhibitor that reduces left ventricular outflow tract gradients by mitigating cardiac hypercontractility. METHODS: In this phase 3, double-blind trial, we randomly assigned adults with symptomatic obstructive HCM to receive aficamten (starting dose, 5 mg; maximum dose, 20 mg) or placebo for 24 weeks, with dose adjustment based on echocardiography results. The primary end point was the change from baseline to week 24 in the peak oxygen uptake as assessed by cardiopulmonary exercise testing. The 10 prespecified secondary end points (tested hierarchically) were change in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS), improvement in the New York Heart Association (NYHA) functional class, change in the pressure gradient after the Valsalva maneuver, occurrence of a gradient of less than 30 mm Hg after the Valsalva maneuver, and duration of eligibility for septal reduction therapy (all assessed at week 24); change in the KCCQ-CSS, improvement in the NYHA functional class, change in the pressure gradient after the Valsalva maneuver, and occurrence of a gradient of less than 30 mm Hg after the Valsalva maneuver (all assessed at week 12); and change in the total workload as assessed by cardiopulmonary exercise testing at week 24. RESULTS: A total of 282 patients underwent randomization: 142 to the aficamten group and 140 to the placebo group. The mean age was 59.1 years, 59.2% were men, the baseline mean resting left ventricular outflow tract gradient was 55.1 mm Hg, and the baseline mean left ventricular ejection fraction was 74.8%. At 24 weeks, the mean change in the peak oxygen uptake was 1.8 ml per kilogram per minute (95% confidence interval [CI], 1.2 to 2.3) in the aficamten group and 0.0 ml per kilogram per minute (95% CI, -0.5 to 0.5) in the placebo group (least-squares mean between-group difference, 1.7 ml per kilogram per minute; 95% CI, 1.0 to 2.4; P<0.001). The results for all 10 secondary end points were significantly improved with aficamten as compared with placebo. The incidence of adverse events appeared to be similar in the two groups. CONCLUSIONS: Among patients with symptomatic obstructive HCM, treatment with aficamten resulted in a significantly greater improvement in peak oxygen uptake than placebo. (Funded by Cytokinetics; SEQUOIA-HCM ClinicalTrials.gov number, NCT05186818.).
- MeSH
- aplikace orální MeSH
- benzylaminy MeSH
- dvojitá slepá metoda MeSH
- hypertrofická kardiomyopatie * farmakoterapie patofyziologie MeSH
- kardiovaskulární látky * farmakologie terapeutické užití MeSH
- kontrakce myokardu účinky léků fyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- obstrukce výtoku ze srdeční komory farmakoterapie patofyziologie etiologie MeSH
- senioři MeSH
- spotřeba kyslíku účinky léků MeSH
- srdeční myosiny antagonisté a inhibitory MeSH
- tolerance zátěže účinky léků MeSH
- uracil analogy a deriváty MeSH
- Valsalvův manévr 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
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
S odvoláním na práci Yanga et al. (36) se v odborném tisku objevila doporučení jak odhalit riziko náhlé srdeční příhody pomocí jednoduchého motorického testu – schopnosti provést určitý počet kliků. Uvedená studie ukázala, že vyšší počet nepřetržitě provedených kliků (40 kliků a více) je v kohortě hasičů spojen s nižším výskytem kardiovaskulárních onemocnění (KVO) ve srovnání s těmi, kteří dosáhli méně než 10 kliků. Vyšší incidence KVO u skupiny nejméně výkonných hasičů však pravděpodobně souvisela také s dalšími zdravotními problémy a naopak, vyšší silově-vytrvalostní výkonnost v prevenci KVO není tím rozhodujícím faktorem. Navržený „klikový“ test tak může sloužit jako orientační snadno proveditelný screening k odhalení ohrožených osob.
Referring to the work of Yang et al. (36) several professional sources recommended how to detect the risk of a sudden heart attack using a simple motor test – the ability to perform a certain number of push-ups. The study showed that higher baseline push-up capacity (40 push-ups and more) in the cohort of firefighters is associated with lower incidence of cardiovascular diseases (CVD) compared with those completing less then 10 push-ups. However, the higher incidence of CVD events in the group of least powerful firefighters is probably also related to other health problems, and conversely, higher strength endurance performance in the prevention of CVD diseases is not the decisive factor. The proposed push-up test can thus serve as an orientation easy-to-perform screening to detect endangered persons.
- Klíčová slova
- "test 40 kliků",
- MeSH
- hasiči MeSH
- kardiovaskulární nemoci * prevence a kontrola MeSH
- lidé MeSH
- spotřeba kyslíku MeSH
- věkové faktory MeSH
- zátěžový test * metody MeSH
- Check Tag
- lidé MeSH
Regadenoson je selektivního A2A adenosin umožňující farmakologicky zatížit pacienty, u nichž by fyzická zátěž byla nemožná nebo jen velmi obtížná. Jsou prezentovány dvě kazuistiky demonstrující výhody tohoto preparátu. V prvním případě jsme se u 77letého muže po aortokoronárním bypassu nejprve pokoušeli o fyzickou zátěž, která byla pro nedostatečný vzestup tepové frekvence ihned změněna na zátěž farmakologickou. Během pokračující nižší úrovně fyzické zátěže byl aplikován regadenoson. Jednofotonová emisní tomografie (SPECT) zobrazila rozsáhlou ischemii laterální stěny a koronarografie následně prokázala uzávěr žilního štěpu na ramus circumflexus. Druhá kazuistika demonstruje současný pokrok technologie SPECT. Na moderních multidetektorových kadmium zinek telluridových (Cadmium Zinc Telluride, CZT) kamerách lze nahrávat dynamicky a kvantifikovat koronární průtokovou rezervu (coronary flow reserve, CFR), což může pomoci při identifikaci nemoci více koronárních tepen nebo mikrovaskulární ischemie. CFR se stanovuje jako poměr myokardiálního průtoku po vazodilataci navozené farmakologickou zátěži a v klidu. 50letý diabetik má na konvenčním SPECT myokardu normální pozátěžovou perfuzi i funkci levé komory. Dynamický SPECT prokázal normální hodnoty myokardiálního krevního průtoku (myocardial blood flow, MBF) i normální CFR ≥ 2. Během 18 měsíců sledování jsme u něj nezaznamenali kardiální příhodu.
Regadenoson as a selective A2A adenosine enables pharmacological stress when exercise stress techniques would be impossible or very difficult. We present two case reports demonstrating its advantages. In case 1, we initially attempted to induce stress using physical exercise in a 77-year-old male patient after coronary artery bypass graft. Due to inadequate heart rate increase, the stress was promptly converted to pharmacological stress using regadenoson in combination with a low level of exercise. Single-photon emission computed tomography (SPECT) showed extensive ischaemia of the lateral wall. Coronary angiography subsequently revealed vein graft occlusion at the left circumflex artery. Case 2 demonstrates recent advances in SPECT technology. Modern multidetector Cadmium Zinc Telluride (CZT) cameras enable dynamic acquisition and quantification of coronary flow reserve (CFR). It can be helpful in identifying multivessel disease or microvascular ischaemia. CFR is calculated as the ratio between myocardial blood flow during stress vasodilator hyperaemia and flow at rest. In a 50-year-old diabetic patient, a conventional cardiac SPECT showed normal post-stress left ventricular perfusion and function. Dynamic SPECT showed normal myocardial blood flow (MBF) and normal CFR ≥ 2. During 18 months of follow-up, no cardiac event was observed in this patient.
- Klíčová slova
- regadenoson,
- MeSH
- agonisté adenosinového receptoru A2 MeSH
- jednofotonová emisní výpočetní tomografie * metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- vazodilatancia MeSH
- zátěžový test metody MeSH
- zobrazování myokardiální perfuze metody MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- kazuistiky MeSH
