Aims
The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is being tested in the Global ...Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials.
Methods and results
Adults with established HFrEF, New York Heart Association (NYHA) functional class ≥II, ejection fraction ≤35%, elevated natriuretic peptides and either current hospitalization for heart failure or history of hospitalization/emergency department visit for heart failure within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5, or 50 mg bid). A total of 8256 patients male (79%), non‐white (22%), mean age 65 years were enrolled with a mean ejection fraction 27%, ischaemic aetiology in 54%, NYHA class II 53% and III/IV 47%, and median N‐terminal pro‐B‐type natriuretic peptide 1971 pg/mL. Heart failure therapies at baseline were among the most effectively employed in contemporary heart failure trials. GALACTIC‐HF randomized patients representative of recent heart failure registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure <100 mmHg (n = 1127), estimated glomerular filtration rate <30 mL/min/1.73 m2 (n = 528), and treated with sacubitril/valsartan at baseline (n = 1594).
Conclusions
GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation.
Graphical representation of the GALACTIC‐HF trial design, enrolment and baseline characteristics. ACEi, angiotensin‐converting enzyme inhibitor; ARB, angiotensin receptor blocker; ARNi, angiotensin receptor–neprilysin inhibitor; CRT, cardiac resynchronization therapy (biventricular pacemaker); CV, cardiovascular; EF, ejection fraction; HFrEF, heart failure with reduced ejection fraction; ICD, implantable cardioverter defibrillator; NT‐proBNP, N‐terminal pro‐B‐type natriuretic peptide; NYHA, Hew York Heart Association; SBP, systolic blood pressure.
Aim
N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) is predictive of both outcomes and response to treatment in patients with heart failure with reduced ejection fraction (HFrEF). The aim of ...this study was to examine the effect of the cardiac myosin activator omecamtiv mecarbil according to baseline NT‐proBNP level in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure trial (GALACTIC‐HF).
Methods and results
The primary outcome was the composite of a worsening heart failure event (urgent clinic visit, emergency department visit, or hospitalization) or cardiovascular death. We prespecified analysis of the effect of treatment according to baseline NT‐proBNP (≤ median, > median), excluding individuals with atrial fibrillation/flutter (AF/AFL). Of the 8232 patients analysed, 8206 had an available baseline NT‐proBNP measurement. Among the 5971 patients not in AF/AFL, the median (Q1–Q3) NT‐proBNP level was 1675 (812–3579) pg/ml. Hazard ratios (HR) for the effect of omecamtiv mecarbil, compared with placebo, for the primary endpoint in patients without AF/AFL were: ≤ median 0.94 (95% confidence interval CI 0.80–1.09), > median 0.81 (0.73–0.90) (p‐interaction = 0.095); for the overall population (including patients with AF/AFL) the HRs were ≤ median 1.01 (0.90–1.15) and > median 0.88 (0.80–0.96) (p‐interaction = 0.035). There was an interaction between treatment and NT‐proBNP, examined as a continuous variable, with greater effect of omecamtiv mecarbil on the primary outcome in patients with a higher baseline NT‐proBNP (p‐interaction = 0.086).
Conclusions
In GALACTIC‐HF, the benefit of omecamtiv mecarbil appeared to be larger in patients with higher baseline NT‐proBNP levels, especially in patients without AF/AFL.
Clinical Trial Registration: ClinicalTrials.gov Identifier NCT02929329; EudraCT number, 2016‐002299‐28.
Abstract Background In patients with an acute coronary syndrome (ACS), no conclusive agreement has been reached to date regarding the association between the different types of atrial fibrillation ...(AF) and the in-hospital mortality risk. We conducted a retrospective cohort study in patients with ACS to determine the prognostic implications of the different types of AF. Methods We analyzed 6705 consecutive patients with ACS admitted to a coronary care unit (CCU), including 3094 with ST segment elevation myocardial infarction (STEMI) and 3611 with non-ST-elevation acute coronary syndrome (NSTE-ACS). We identified the patients with pre-existing AF, new-onset AF at admission, and new-onset AF at the CCU. Results The overall incidence of AF was documented in 360 (5.4%) of the patients (STEMI, 5%; NSTE-ACS, 5.6%), 140 (2.1%) of whom had pre-existing AF, and 220 (3.2%) of whom had new-onset AF (AF at admission, 1.3%; AF at the CCU, 1.9%). The patients with AF had high-risk clinical characteristics and developed major adverse events more frequently than did the patients without AF. The unadjusted in-hospital mortality risk was significantly higher in the patients with pre-existing AF (STEMI, 3.79-fold; NSTE-ACS, 3.4-fold) and AF at the CCU (STEMI, 2.02-fold; NSTE-ACS, 8.09-fold). After adjusting for the multivariate analysis, only the AF at the CCU in the NSTE-ACS group was associated with a 4.40-fold increase in the in-hospital mortality risk (odds ratio 4.40, CI 1.82–10.60, p = 0.001). In the STEMI group, the presence of any type of AF was not associated with an increased risk of mortality. Conclusion Among the different types of AF in patients with ACS, only the new-onset AF that developed during the CCU stay in patients with NSTE-ACS was associated with a 4.40-fold increase in the in-hospital mortality risk.
Aims
Little is known regarding acute heart failure (AHF) clinical characteristics and its hospital outcome in Latin America. This study sought to assess the prevalence of, and identify differences ...among, in‐hospital outcomes in patients hospitalized for AHF who were stratified by clinical phenotype at a hospital in Latin America.
Methods and results
This is a retrospective cohort study of patients with AHF who were hospitalized in the coronary care unit of a Latin American teaching hospital from January 2006 to December 2018. Cox regression analysis was used to identify predictors of mortality. Of 21 042 patients admitted, 7759 (36.6%) had AHF. Their median age was 62 years, and 35% were women. De novo heart failure was seen in 39.4% of patients. Most common was AHF‐associated acute coronary syndromes (ACS‐HF) in 43.0%, decompensated heart failure (DHF) in 33.7%, hypertensive heart failure (HT‐HF) in 11.8%, and cardiogenic shock (CS) in 5.2%. Pulmonary oedema (PO) (3.3%) and right heart failure (RHF) (3.0%) were least frequent. Coronary artery disease was the most frequent aetiology in 56.5% of patients, valvular heart disease in 22.4%, and cardiomyopathies in 12.3%. Other less frequent aetiology included adult congenital heart disease (2.5%), lung diseases (2.1%), acute aortic syndromes (1.4%), pericardial diseases (0.8%), and intracardiac tumours (0.3%). Aetiology could not be established in 1.6% of patients. Before admission, patients with worsening chronic heart failure and reduced ejection fraction were treated with renin–angiotensin system blockers (60.4%), beta‐blockers (42.5%), or spironolactone (34.4%). The percentages of patients given in‐hospital management with intravenous diuretics, vasodilators, inotropes, and vasopressors were 81.2%, 33.4%, 18.9%, and 20.4%, respectively. The overall in‐hospital mortality was 17.9% (71.3%, 43.9%, 23.8%, 14.9%, 13.6%, and 10.1% for CS, PO, RHF, DHF, ACS‐HF, and HT‐HF, respectively; P < 0.0001). Multivariate analysis revealed that PO (hazard ratio HR 2.68, 95% confidence interval CI 1.73–4.14, P < 0.0001) and CS (HR 3.37, 95% CI 2.12–5.35, P < 0.0001) were independent predictors of in‐hospital mortality. Use of intravenous diuretics was linked to reduction of in‐hospital mortality (HR 0.70, 95% CI 0.59–0.59, P < 0.0001). By contrast, increased in‐hospital mortality was associated with the use of intravenous inotrope or vasopressor (HR 1.49, 95% CI 1.27–1.76 and HR 2.91, 95% CI 2.41–3.51, P < 0.0001, respectively).
Conclusions
Real‐world evidence from a university hospital in Latin America shows that the high mortality among patients with AHF may depend, among other factors, on patients' AHF clinical phenotypes. The clinical characteristics and aetiologies of AHF appear to differ between these data from Mexico and those from European and US registries.
Objetivo: Evaluar la asociación entre la circulación coronaria colateral y la función contráctil ventricular en pacientes con infarto agudo de miocardio no reperfundido. Método: Estudio observacional ...descriptivo y retrospectivo en pacientes con infarto agudo de miocardio con elevación del segmento ST (IAMCEST) en un centro cardiovascular de referencia, de enero de 2006 a diciembre de 2022. Se analizaron las coronariografías y los ecocardiogramas para evaluar la circulación coronaria colateral y la función ventricular, respectivamente. Se dividieron en grupos de acuerdo con la presencia de circulación colateral. Se compararon ambos grupos y se analizó la mortalidad durante la hospitalización del evento índice. Resultados: De 14,985 pacientes con síndrome coronario agudo, 8134 (54.3%) presentaron IAMCEST. Se excluyeron 12,880, quedando así 2105 pacientes con IAMCEST no reperfundidos y sometidos a coronariografía, revelando lesiones. Hubo más pacientes sin circulación colateral: 1547 (73.5%) vs. 558 (26.5%) (p = 0.025). Los pacientes sin circulación colateral presentaron una mayor fracción de eyección ventricular izquierda (mediana del 47% vs. 42%; p < 0.001). La mortalidad en los pacientes con circulación colateral fue mayor que en los pacientes sin ella (11.6% vs. 9.8%; p = 0.225), pero no se alcanzó significancia estadística. Conclusiones: Los pacientes con IAMCEST no reperfundidos no presentaron protección por la circulación colateral al evaluar la función sistólica ventricular izquierda. No se encontró diferencia en la mortalidad en comparación con la población sin desarrollo de circulación colateral.
•Our findings provide support to the concepts of inflammation in clinical practice.•The inflammation-based risk score has got the ability to predict in-hospital mortality in acute coronary ...syndrome.•Approximately one-fifth of these patients had severe systemic inflammation.•The patients with severe inflammation had significantly poorer in-hospital outcomes.•Presence of severe inflammation may provide reasons for new anti-inflammatory strategies.
Accurate assessment of inflammatory status of patients during acute coronary syndrome (ACS) has become of great importance in their risk classification and in the research of new anti-inflammatory therapies.
The study cohort included 7396 patients with ACS. We sought to derive and internally validate an inflammation-based score that included high-sensitivity C-reactive protein, white blood cell count, and serum albumin level at admission to evaluate the predictive role of systemic inflammation in the clinical outcome of these patients. We randomly assigned patients into derivation (66.6%) and validation (33.4%) cohorts. A total of four categories of systemic inflammation were defined.
Assessed individually, the three biomarkers were associated with a higher rate of in-hospital mortality. When we combined them into an inflammation score, in-hospital mortality was significantly different across the four categories of inflammation in the derivation cohort (1.8%, 2.8%, 4.1%, and 13.8% for without, mild, moderate, and severe inflammation, respectively; p<0.0001, C-statistic, 0.71). These results were similar in the validation cohort (1.1%, 2.9%, 5.2%, and 12.6%, respectively; p<0.0001, C-statistic, 0.71). After multivariate adjustment, only the category of severe systemic inflammation was associated with a threefold increased risk of in-hospital mortality (odds ratios 3.02, p<0.0001) and was the most powerful predictor of mortality. In the whole cohort, after subsetting patients based on GRACE risk score, the severe inflammation category was associated with a significant increase of in-hospital mortality across all sub-groups, mainly in patients with higher GRACE risk score. The inflammation-based risk score reclassified 25.3% of the population. The net reclassification index was 8.2% (p=0.001).
A risk score system based on biomarkers of inflammation readily available at admission in patients with ACS, could better assess the inflammatory status and predict in-hospital mortality, as well as severe systemic inflammation that contributes to a worse outcome independently of clinical risk factors.
The role of ABO gene polymorphisms in acute coronary syndrome (ACS) and lipid metabolism is increasingly recognized. We investigated whether ABO gene polymorphisms are significantly associated with ...ACS and the plasma lipid profile. Six ABO gene polymorphisms (rs651007 T/C, rs579459 T/C, rs495928 T/C, rs8176746 T/G, rs8176740 A/T, and rs512770 T/C) were determined by 5'exonuclease TaqMan assays in 611 patients with ACS and 676 healthy controls. The results demonstrated that the rs8176746 T allele was associated with a lower risk of ACS under the co-dominant, dominant, recessive, over-dominant, and additive models (P=0.0004, P=0.0002, P=0.039, P=0.0009, and P=0.0001, respectively). Furthermore, under co-dominant, dominant, and additive models, the rs8176740 A allele was associated with a lower risk of ACS (P=0.041, P=0.022, and P=0.039, respectively). On the other hand, the rs579459 C allele was associated with a lower risk of ACS under the dominant, over-dominant, and additive models (P=0.025, P=0.035, and P=0.037, respectively). In a subanalysis performed with the control group, rs8176746 T and rs8176740 A alleles were associated with low systolic blood pressure and with both high HDL-C and low triglyceride plasma concentrations, respectively. In conclusion, ABO gene polymorphisms were associated with a lower risk of ACS, and lower systolic blood pressure and plasma lipid levels, suggesting a causal relationship between ABO blood groups and the incidence of ACS.
Aims The Society of Cardiovascular Angiography and Interventions (SCAI) shock stages have been applied and validated in high-income countries with access to advanced therapies. We applied the SCAI ...scheme at the time of admission in order to improve the risk stratification for 30-day mortality in a retrospective cohort of patients with STEMI in a middle-income country hospital at admission. Methods This is a retrospective cohort study, we analyzed 7,143 ST-segment elevation myocardial infarction (STEMI) patients. At admission, patients were stratified by the SCAI shock stages. Multivariate analysis was used to assess the association between SCAI shock stages to 30-day mortality. Results The distribution of the patients across SCAI shock stages was 82.2%, 9.3%, 1.2%, 1.5%, and 0.8% to A, B, C, D, and E, respectively. Patients with SCAI stages C, D, and E were more likely to have high-risk features. There was a stepwise significant increase in unadjusted 30-day mortality across the SCAI shock stages (6.3%, 8.4%, 62.4%, 75.2% and 88.3% for A, B, C, D and E, respectively; P < 0.0001, C-statistic, 0.64). A trend toward a lower 30-day survival probability was observed in the patients with advanced CS (30.3, 15.4%, and 8.3%, SCAI shock stages C, D, and E, respectively, Log-rank P-value <0.0001). After multivariable adjustment, SCAI shock stages C, D, and E were independently associated with an increased risk of 30-day death (hazard ratio 1.42 P = 0.02, 2.30 P<0.0001, and 3.44 P<0.0001, respectively). Conclusion The SCAI shock stages applied in patients con STEMI at the time of admission, is a useful tool for risk stratification in patients across the full spectrum of CS and is a predictor of 30-day mortality.
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