51 research outputs found
Influence of atrial fibrillation on efficacy and safety of omecamtiv mecarbil in heart failure: the GALACTIC-HF trial
No full textAims:
In GALACTIC-HF, the cardiac myosin activator omecamtiv mecarbil compared with placebo reduced the risk of heart failure events or cardiovascular death in patients with heart failure with reduced ejection fraction. We explored the influence of atrial fibrillation or flutter (AFF) on the effectiveness of omecamtiv mecarbil.
Methods and results:
GALACTIC-HF enrolled patients with New York Heart Association (NYHA) Class II–IV heart failure, left ventricular ejection fraction ≤35%, and elevated natriuretic peptides. We assessed whether the presence or absence of AFF, a pre-specified subgroup, modified the treatment effect for the primary and secondary outcomes, and additionally explored effect modification in patients who were or were not receiving digoxin. Patients with AFF (n = 2245, 27%) were older, more likely to be randomized as an inpatient, less likely to have a history of ischaemic aetiology or myocardial infarction, had a worse NYHA class, worse quality of life, lower estimated glomerular filtration rate, and higher N-terminal pro-B-type natriuretic peptide. The treatment effect of omecamtiv mecarbil was modified by baseline AFF (interaction P = 0.012), with patients without AFF at baseline deriving greater benefit. The worsening of the treatment effect by baseline AFF was significantly more pronounced in digoxin users than in non-users (interaction P = 0.007); there was minimal evidence of effect modification in those patients not using digoxin (P = 0.47) or in digoxin users not in AFF.
Conclusion:
Patients in AFF at baseline were less likely to benefit from omecamtiv mecarbil than patients without AFF, although the attenuation of the treatment effect was disproportionally concentrated in patients with AFF who were also receiving digoxin.
Clinical Trial Registration: NCT02929329
Atrial cardiomyopathy in postmenopausal female healthcare professionals – a single-center study
No full textВъведение: Добре проучено е разпространението на затлъстяването и хипертонията сред здравните работници. И двете заболявания са известни като рискови фактори за предсърдна кардиомиопатия (ПКМП) – нова клинична единица с потенциал да предизвиква сърдечна недостатъчност, предсърдно мъждене и тромбоемболични усложнения. В тази връзка е необходимо планирането на превантивни стратегии и интервенции при тази специфична популация. Цел: Да се дефинира ПКМП при здравни работници от женски пол в менопауза. Материал и методи: Сто и пет жени на средна възраст, здравни работници, разделени в три групи: с централно затлъстяване (n = 50, 47%), със затлъстяване и хипертония (n = 24, 23%) и здрави контроли (n = 31, 30%), преминаха през ехокардиографско изследване с волуметричен и speckle tracking анализ. Резултати: Установиха се значителни разлики в обемите на лявото предсърдие (ЛП) между трите групи. Фазовата функция на ЛП беше значително намалена, а stiffness индексът значително увеличен при групите със затлъстяване. По-високият индекс на телесната маса беше свързан с увеличен индексиран максимален обем на ЛП (p < 0.001, r = 0.56) и редуциран пиков лонгитудинален стрейн на ЛП (p < 0.001, r = -0.59) и пиков контрактилен стрейн на ЛП (p < 0.001, r = -0.56). Заключение: Здравните работници от женски пол в менопауза със затлъстяване и хипертония са в риск от асимптомна ПМКП. Необходими са допълнителни изследвания за потвърждаване на тази концепция. Background: The prevalence of obesity and hypertension among healthcare professionals has been previously described. Both diseases are known risk factors for atrial cardiomyopathy (ACM), a new clinical entity with potential to be a determinant of heart failure, atrial fi brillation and thromboembolic complications. In this perspective, early preventive strategy should be initiated in this special population. Aim: To defi ne ACM in middle-aged women healthcare professionals. Material and methods: Hundred and fi ve middle-aged women healthcare professionals, separated in 3 groups: with central obesity (n = 50,47%), obesity and hypertension (n = 24,23%), healthy control (n = 31,30%), underwent echocardiographic examination with volumetric and speckle-tracking analysis. Results: There were signifi cant differences in LA volumes between 3 groups. LA phasic function was signifi cantly reduced, and LA stiffness index was signifi cantly increased in obese groups compared to control. Higher body mass index was associated with increased LA volume index (p < 0.001, r = 0.56) and with reduced Peak atrial longitudinal strain (p < 0.001, r = -0.59) and Peak atrial contractile strain (p < 0.001, r= -0.56). Conclusion: Postmenopausal women, healthcare professionals with obesity and hypertension are at risk for asymptomatic ACM. Further investigations are needed to confi rm this concept
Advantages of left atrial mechanic assessment as an additional indicator of diastolic dysfunction in patients with arterial hypertension
No full textУвод: Артериалната хипертония е най-често срещаният фактор за структурни и функционални промени в сърдечните кухини, но тези изменения се наблюдават в по-напреднали стадии и при пациенти с лош контрол на артериалната хипертония. Ехокардиографията има ключова роля за установяване на тези промени, но за откриване на ранни промени е необходима по-детайлна оценка. Все още се доказва ролята на ЛП механика, като допълнителен показател за диастолна дисфункция, особено за пациенти, при които стандартните ехокардиографски показатели са с гранични стойности и неубедителни. Цел: Целта на нашето проучване е да се изследват левопредсърдната механика и структурните и функционални показатели на ЛК при пациенти с контролирана артериална хипертония с давност от 5 години. Материал и методи: Проведе се едноцентрово проучване с 45 пациенти с лека към умерена хипертония (с давност до 5 години) и 15 здрави контроли. Всички параметри за 24-часово проследяване на съдовата ригидност: централно систолно налягане (cSys24h), централно пулсово налягане (cPP24h) и скорост на пулсовата вълна (PWV24h), са измерени неинвазивно с апарат Mobil-O-graph PWA. Пациентите преминаха през стандартна двуразмерна ехокардиография със spеckle tracking анализ ЛК (LV-GLS) и ЛП резервоарен лонгитудинален стрейн (LA-RLS). Резултати: Пациентите с хипертония имат концентрична ЛК хипертрофия (КЛХ), измерена чрез RWT (p < 0,001), редуциран LV-GLS (-15,83 ± 3,17 спрямо -17,57 ± 2,83, p < 0,001). Забелязва се тенденция към по- високи налягания на пълнене Е/e’m ratio (9,84 ± 2,85 vs. 7,62 ± 1,58, p < 0,006), по-голям ЛП обем (LAVI: 31,86 ± 9,78 vs. 24,96 ± 4,89 ml/m2, p < 0,011) и редуциран LA-GLS (29,14 ± 3,90 спрямо 41,33 ± 4,37%, p < 0,0001) в сравнение с контролната група. Силно позитивна връзка се установи между скоростта на пулсовата вълна за 24 часа (PWV24h) и ЛК концентрична хипертрофия, измерена чрез RWT (r = 0,545, p<0,0001). Установи се умерено позитивна връзка между cSys24h и ЛК концентрична хипертрофия (r = 0,333, p = 0,009) и слабо негативна връзка с LA-RLS (r = -0,221, p = 0, 09). E/e’m корелира позитивно с LAVI (r = 0,309, p = 0,016) и негативно с LA-RLS (r = -0,324, p=0,012). От проведения множествен регресионен линеен анализ се установи, че най-силни независими предиктори на LA-GLS са PWV24h (R=0,459, B= -4,59, p < 0,0001) и Е/e’m: (R=0,535, B = -291, p = 0,017). Независим предиктор за ЛК хипертрофия, определена чрез RWT, са PWV24h (R = 0,488, B = 238, p < 0,0001) и Е/e’m (R = 0,561, B = 263, p = 0,022). Заключение: Показателите на ЛП механика имат допълнителна диагностична стойност при оценката на диастолната функция там, където стандартните показатели за диастолна функция не са достатъчно убедителни. При пациенти с контролирана АХ се наблюдават ранни промени в оста атрио-вентрикуло-съдово куплиране. Background: Arterial hypertension is the most common factor for structural and functional changes in the heart, but these changes are observed in more advanced stages and in patients with poor control of arterial hypertension. Echocardiography plays a key role in detecting these changes, but a more detailed assessment is needed to identify early changes. The role of left atrium mechanics as an additional indicator of diastolic dysfunction is still being proven, especially for patients in whom standard echocardiographic indicators are borderline and inconclusive. Aim: The aim of our study is to investigate the left atrial mechanics and the structural and functional parameters of the LC in patients with controlled arterial hypertension with a period of 5 years. Material and methods: We studied 45 consecutive middle-aged patients with mild to moderate hypertension and duration up to 5 years and 15 healthy controls. All parameters for arterial stiffness – 24-hour central systolic pressure (cSys24h), central pulse pressure (cPP24h) and 24-hour pulse wave velocity (PWV24h) were measured non – invasively with oscillometric method by Mobil-O-graph PWA. All patients underwent standard two-dimensional echocardiography with spackle tracking analysis for left ventricle (LV) and left atrium (LA) global longitudinal strain (GLS). Results: The patients with hypertension have concentric LV hypertrophy, measured by RWT (p < 0,001), reduced LV GLS (-15,83 ± 3,17 vs. -17,57 ± 2,83, p < 0,001). There is a tendency towards higher fi lling pressures E/e’m ratio (9,84 ± 2,85 vs. 7,62 ± 1,58, p = 0,006), dilated LA (LAVI: 31,86 ± 9,78 vs. 24,96 ± 4,89 ml/m2, p < 0,011) and reduced LA - GLS (29,14 ± 3,90 vs. 41,33 ± 4,37%, p < 0,0001) in comparison to control group. Strongly positive correlation is registered between PWV24h and LV concentric hypertrophy indicated as RWT (r = 0,545, p < 0,0001) There is positive correlation between cSys24h and LV concentric hypertrophy (r = 0,333, p = 0,009) and negative correlation with LA-GLS (r = -0,221, p = 0,09). E/e’ correlated positively with LAVI (r = 0,309, p = 0,016) and negatively with LA-GLS (r = 0,324, p=0,012). Multiple linear regression with multivariate models were used to estimate RWT and LA-GLS. We initially selected clinically relevant variables and known confounders for inclusion in the multivariable regression analysis, using stepwise logistic regression analysis we found that the most powerful predictors for LA-GLS are PWV24h (R = 0,459, B = -4,59, p < 0,0001) and Е/e’m: (R = 0,535, B = -291, p = 0,017). The most powerful predictor for LV hypertrophy, determine by RWT is PWV24h (R = 0,488, B = 238, p< 0,0001) and Е/e’ m (R = 0,561, B = 263, p = 0,022). Conclusion: Left atrial mechanics indicators have additional diagnostic value in assessing diastolic function, where standard indicators of diastolic function are not suffi ciently conclusive. In patients with controlled AH, early changes in the atrio-ventruculo-vascular coupling axis are observed
Quality of Life and Mental Health in Patients with Exacerbated Heart Failure: The Role of Obstructive and Central Sleep Apnea Phenotypes
No full textBackground: Managing acute decompensated heart failure (ADHF) is complex, particularly when combined with comorbidities like sleep apnea. Effective treatment requires personalized approaches, focusing on quality of life (QoL) and mental health outcomes. Purpose: This study explored the prevalence and characteristics of sleep apnea in patients with obesity and AHF exacerbations. It assessed how different sleep apnea phenotypes impact QoL and mental health, applying personalized medicine strategies. Methods: A prospective cohort study was conducted on 150 patients admitted for AHF exacerbation. Inclusion criteria included an Apnea–Hypopnea Index (AHI) > 5, an Epworth Sleepiness Scale (ESS) > 8, NT-proBNP > 900 pg/mL and informed consent obtained prior to participation. Optimized medical treatment was provided. QoL and mental health were evaluated using the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the Beck Depression Inventory (BDI). Results: Among 81 patients with sleep apnea, 73% (n = 59) had obstructive sleep apnea (OSA) and 27% (n = 19) had central sleep apnea (CSA). OSA patients reported a higher QoL (61.12 ± 17.88) compared to CSA patients (37.18 ± 19.98, p < 0.001). CSA patients exhibited more severe depression (BDI: 26.18 ± 5.5 vs. 16.64 ± 4.1, p < 0.001). Significant correlations were noted between KCCQ and BDI scores (r = −0.849, p < 0.001) and central apnea events (r = −0.485, p < 0.001). Conclusions: Sleep apnea is common in ADHF patients, with CSA being linked to poorer QoL and greater depression. Personalized medicine offers promising strategies to enhance care and outcomes
Design and methodology of POWER, an open-label observation of the effect of primary care interventions on total cardiovascular risk in patients with hypertension
No full textThe Effect of Omecamtiv Mecarbil in Hospitalized Patients as Compared With Outpatients With HFrEF: An Analysis of GALACTIC-HF
No full textBACKGROUND:
In the Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF) trial, omecamtiv mecarbil, compared with placebo, reduced the risk of worsening heart failure (HF) events or cardiovascular death in patients with HF and reduced ejection fraction (HFrEF). The primary aim of this prespecified analysis was to evaluate the safety and efficacy of omecamtiv mecarbil by randomization setting i.e., whether participants were enrolled as outpatients or inpatients.
METHODS AND RESULTS:
Patients were randomized either during a HF hospitalization or as an outpatient, within one year of a worsening HF event (hospitalization or emergency department [ED] visit). The primary outcome was a composite of worsening HF event (HF hospitalization or an urgent ED or clinic visit) or cardiovascular death. Of the 8232 patients analyzed, 2084 (25%) were hospitalized at randomization. Hospitalized patients had higher NT-proBNP concentrations, lower systolic blood pressure, reported more symptoms and were less frequently treated with a renin-angiotensin system blocker or a beta-blocker than outpatients. The rate (per 100 person-years [PY]) of the primary outcome was higher in hospitalized patients (placebo group=38.3/100 PY) than in outpatients (23.1/100 PY); adjusted hazard ratio (HR) 1.21 (95%CI 1.12, 1.31). The effect of omecamtiv mecarbil versus placebo on the primary outcome was similar in hospitalized patients (HR 0.89, 95%CI 0.78, 1.01) and outpatients (HR 0.94, 95%CI 0.86, 1.02) (interaction P=0.51).
CONCLUSION:
Hospitalized HFrEF patients had a higher rate of the primary outcome than outpatients. Omecamtiv mecarbil reduced the risk of the primary outcome both when initiated in hospitalized patients and in outpatients
Effect of Antihypertensive Therapy on SCORE-Estimated Total Cardiovascular Risk: Results from an Open-Label, Multinational Investigation—The POWER Survey
No full textBackground. High blood pressure is a substantial risk factor for cardiovascular disease. Design & Methods. The Physicians' Observational Work on patient Education according to their vascular Risk (POWER) survey was an open-label investigation of eprosartan-based therapy (EBT) for control of high blood pressure in primary care centers in 16 countries. A prespecified element of this research was appraisal of the impact of EBT on estimated 10-year risk of a fatal cardiovascular event as determined by the Systematic Coronary Risk Evaluation (SCORE) model. Results. SCORE estimates of CVD risk were obtained at baseline from 12,718 patients in 15 countries (6504 men) and from 9577 patients at 6 months. During EBT mean (±SD) systolic/diastolic blood pressures declined from 160.2 ± 13.7/94.1 ± 9.1 mmHg to 134.5 ± 11.2/81.4 ± 7.4 mmHg. This was accompanied by a 38% reduction in mean SCORE-estimated CVD risk and an improvement in SCORE risk classification of one category or more in 3506 patients (36.6%). Conclusion. Experience in POWER affirms that (a) effective pharmacological control of blood pressure is feasible in the primary care setting and is accompanied by a reduction in total CVD risk and (b) the SCORE instrument is effective in this setting for the monitoring of total CVD risk
Chronic oral study of myosin activation to increase contractility in heart failure (COSMIC-HF): a phase 2, pharmacokinetic, randomised, placebo-controlled trial
No full textBackground:
Impaired contractility is a feature of heart failure with reduced ejection fraction. We assessed the pharmacokinetics and effects on cardiac function and structure of the cardiac myosin activator, omecamtiv mecarbil.
Methods:
In this randomised, double-blind study, done at 87 sites in 13 countries, we recruited patients with stable, symptomatic chronic heart failure and left ventricular ejection fraction 40% or lower. Patients were randomly assigned equally, via an interactive web response system, to receive 25 mg oral omecamtiv mecarbil twice daily (fixed-dose group), 25 mg twice daily titrated to 50 mg twice daily guided by pharmacokinetics (pharmacokinetic-titration group), or placebo for 20 weeks. We assessed the maximum concentration of omecamtiv mecarbil in plasma (primary endpoint) and changes in cardiac function and ventricular diameters. This trial is registered with ClinicalTrials.gov, number NCT01786512.
Findings:
From March 17, 2014, to March 5, 2015, we enrolled 150 patients in the fixed-dose omecamtiv mecarbil group and 149 in the pharmacokinetic-titration and placebo groups. Mean maximum concentration of omecamtiv mecarbil at 12 weeks was 200 (SD 71) ng/mL in the fixed-dose group and 318 (129) ng/mL in the pharmacokinetic-titration group. For the pharmacokinetic-titration group versus placebo group at 20 weeks, least square mean differences were as follows: systolic ejection time 25 ms (95% CI 18–32, p<0·0001), stroke volume 3·6 mL (0·5–6·7, p=0·0217), left ventricular end-systolic diameter −1·8 mm (−2·9 to −0·6, p=0·0027), left ventricular end-diastolic diameter −1·3 mm, (−2·3 to 0·3, p=0·0128), heart rate −3·0 beats per min (−5·1 to −0·8, p=0·0070), and N-terminal pro B-type natriuretic peptide concentration in plasma −970 pg/mL (−1672 to −268, p=0·0069). The frequency of adverse clinical events did not differ between groups.
Interpretation:
Omecamtiv mecarbil dosing guided by pharmacokinetics achieved plasma concentrations associated with improved cardiac function and decreased ventricular diameter
Patiromer for Heart Failure Medication Optimization in Patients With Current or Past Hyperkalemia: DIAMOND Subanalysis
No full textBackground: For heart failure with reduced ejection fraction (HFrEF), suboptimal use of renin-angiotensin-aldosterone system inhibitors (RAASis), including mineralocorticoid receptor antagonists (MRAs), due to hyperkalemia, may be improved by potassium binders. Objectives: This prespecified analysis of the phase 3 DIAMOND (Patiromer for the Management of Hyperkalemia in Subjects Receiving RAASi Medications for the Treatment of Heart Failure) trial assessed the effect of patiromer in patients with HFrEF and either current or past hyperkalemia. Methods: Patients with HFrEF and current or past (within 1 year before enrollment) hyperkalemia (serum potassium [sK+] >5.0 mmol/L) entered a single-blind, run-in phase to optimize RAASis while receiving patiromer. They were subsequently randomized, double-blind, to continue patiromer or change to placebo. Results: Of the 1,038 patients who completed run-in, 354 (83.9%) of 422 with current hyperkalemia and 524 (85.1%) of 616 with past hyperkalemia achieved RAASi optimization and were randomized to treatment. During the double-blind phase, patiromer lowered sK+ levels compared with placebo in both the current and past hyperkalemia subgroups: difference in adjusted mean change from baseline: -0.12 (95% CI: -0.17 to -0.07) and -0.08 (95% CI: -0.12 to -0.05), respectively; Pinteraction = 0.166. Patiromer was more effective than placebo in maintaining MRA at target dose in patients with current vs past hyperkalemia (HR: 0.45 [95% CI: 0.26-0.76] vs HR: 0.85 [95% CI: 0.54-1.32]; Pinteraction = 0.031). Adverse events were similar between subgroups. Conclusions: The use of patiromer facilitates achieving target doses of RAASis in patients with HFrEF with either current or past hyperkalemia. For those with current hyperkalemia before RAASi optimization, use of patiromer may be more beneficial in helping to maintain sK+ control and achieve MRA target dose. (Patiromer for the Management of Hyperkalemia in Subjects Receiving RAASi Medications for the Treatment of Heart Failure [DIAMOND]; NCT03888066)
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