Abstract
Aims
Hypertension (HTN) is a well-known contributor to cardiovascular disease, including heart failure (HF) and coronary artery disease, and is the leading risk factor for premature death ...world-wide. A J- or U-shaped relationship has been suggested between blood pressure (BP) and clinical outcomes in different studies. However, there is little information about the significance of BP on the outcomes of patients with coronary artery disease and left ventricular dysfunction. This study aimed to determine the relationship between BP and mortality outcomes in patients with ischaemic cardiomyopathy.
Methods and results
The influence of BP during a median follow-up of 9.8 years was studied in a total of 1212 patients with ejection fraction ≤35% and coronary disease amenable to coronary artery bypass grafting (CABG) who were randomized to CABG or medical therapy alone (MED) in the STICH (Surgical Treatment for Ischaemic Heart Failure) trial. Landmark analyses were performed starting at 1, 2, 3, 4, and 5 years after randomization, in which previous systolic BP values were averaged and related to subsequent mortality through the end of follow-up with a median of 9.8 years. Neither a previous history of HTN nor baseline BP had any significant influence on long-term mortality outcomes, nor did they have a significant interaction with MED or CABG treatment. The landmark analyses showed a progressive U-shaped relationship that became strongest at 5 years (χ2 and P-values: 7.08, P = 0.069; 8.72, P = 0.033; 9.86; P = 0.020; 8.31, P = 0.040; 14.52, P = 0.002; at 1, 2, 3, 4, and 5-year landmark analyses, respectively). The relationship between diastolic BP (DBP) and outcomes was similar. The most favourable outcomes were observed in the SBP range 120–130, and DBP 75–85 mmHg, whereas lower and higher BP were associated with worse outcomes. There were no differences in BP-lowering medications between groups.
Conclusion
A strong U-shaped relationship between BP and mortality outcomes was evident in ischaemic HF patients. The results imply that the optimal SBP might be in the range 120–130 mmHg after intervention, and possibly be subject to pharmacologic action regarding high BP. Further, low BP was a marker of poor outcomes that might require other interactions and treatment strategies.
Clinical Trial Registration
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00023595.
BACKGROUND:The risk of sudden cardiac death (SCD) in patients with heart failure after coronary artery bypass graft surgery (CABG) has not been examined in a contemporary clinical trial of surgical ...revascularization. This analysis describes the incidence, timing, and clinical predictors of SCD after CABG.
METHODS:Patients enrolled in the STICH trial (Surgical Treatment of Ischemic Heart Failure) who underwent CABG with or without surgical ventricular reconstruction were included. We excluded patients with prior implantable cardioverter-defibrillator and those randomized only to medical therapy. The primary outcome was SCD as adjudicated by a blinded committee. A Cox model was used to examine and identify predictors of SCD. The Fine and Gray method was used to estimate the incidence of SCD accounting for the competing risk of other deaths.
RESULTS:Over a median follow-up of 46 months, 113 of 1411 patients who received CABG without (n = 934) or with (n = 477) surgical ventricular reconstruction had SCD; 311 died of other causes. The mean left ventricular ejection fraction at enrollment was 28±9%. The 5-year cumulative incidence of SCD was 8.5%. Patients who had SCD and those who did not die were younger and had fewer comorbid conditions than did those who died of causes other than SCD. In the first 30 days after CABG, SCD (n=5) accounted for 7% of all deaths. The numerically greatest monthly rate of SCD was in the 31- to 90-day time period. In a multivariable analysis including baseline demographics, risk factors, coronary anatomy, and left ventricular function, end-systolic volume index and B-type natriuretic peptide were most strongly associated with SCD.
CONCLUSIONS:The monthly risk of SCD shortly after CABG among patients with a low left ventricular ejection fraction is highest between the first and third months, suggesting that risk stratification for SCD should occur early in the postoperative period, particularly in patients with increased preoperative end-systolic volume index or B-type natriuretic peptide.
CLINICAL TRIAL REGISTRATION:URLhttp://www.clinicaltrials.gov. Unique identifierNCT0002359.
This study sought to assess the effect of the addition of coronary artery bypass grafting (CABG) to medical therapy on mode of death in heart failure.
Although CABG therapy is widely used in ischemic ...cardiomyopathy patients, there are no prospective clinical trial data on mode of death.
The STICH (Surgical Treatment for Ischemic Heart Failure ) trial compared the strategy of CABG plus medical therapy to medical therapy alone in 1,212 ischemic cardiomyopathy patients with reduced ejection fraction. A clinical events committee adjudicated deaths using pre-specified definitions for mode of death.
In the STICH trial, there were 462 deaths over a median follow-up of 56 months. The addition of CABG therapy tended to reduce cardiovascular deaths (hazard ratio HR: 0.83; 95% confidence interval CI: 0.68 to 1.03; p = 0.09) and significantly reduced the most common modes of death: sudden death (HR: 0.73; 95% CI: 0.54 to 0.99; p = 0.041) and fatal pump failure events (HR: 0.64; 95% CI: 0.41 to 1.00; p = 0.05). Time-dependent estimates indicate that the protective effect of CABG principally occurred after 24 months in both categories. Deaths post-cardiovascular procedures were increased in CABG patients (HR: 3.11; 95% CI: 1.47 to 6.60), but fatal myocardial infarction deaths were lower (HR: 0.07; 95% CI: 0.01 to 0.57). Noncardiovascular deaths were infrequent and did not differ between groups.
In the STICH trial, the addition of CABG to medical therapy reduced the most common modes of death: sudden death and fatal pump failure events. The beneficial effects were principally seen after 2 years. Post-procedure deaths were increased in patients randomized to CABG, whereas myocardial infarction deaths were decreased.
Oxytocin (OT), the brain's most abundant neuropeptide, plays an important role in social salience and motivation. Clinical trials of the efficacy of OT in autism spectrum disorder (ASD) have reported ...mixed results due in part to ASD's complex etiology. We investigated whether genetic and epigenetic variation contribute to variable endogenous OT levels that modulate sensitivity to OT therapy. To carry out this analysis, we integrated genome‐wide profiles of DNA‐methylation, transcriptional activity, and genetic variation with plasma OT levels in 290 participants with ASD enrolled in a randomized controlled trial of OT. Our analysis identified genetic variants with novel association with plasma OT, several of which reside in known ASD risk genes. We also show subtle but statistically significant association of plasma OT levels with peripheral transcriptional activity and DNA‐methylation profiles across several annotated gene sets. These findings broaden our understanding of the effects of the peripheral oxytocin system and provide novel genetic candidates for future studies to decode the complex etiology of ASD and its interaction with OT signaling and OT‐based interventions.
Lay Summary
Oxytocin (OT) is an abundant chemical produced by neurons that plays an important role in social interaction and motivation. We investigated whether genetic and epigenetic factors contribute to variable OT levels in the blood. To this, we integrated genetic, gene expression, and non‐DNA regulated (epigenetic) signatures with blood OT levels in 290 participants with autism enrolled in an OT clinical trial. We identified genetic association with plasma OT, several of which reside in known autism risk genes. We also show statistically significant association of plasma OT levels with gene expression and epigenetic across several gene pathways. These findings broaden our understanding of the factors that influence OT levels in the blood for future studies to decode the complex presentation of autism and its interaction with OT and OT‐based treatment.
Underuse of guideline-recommended inhaled corticosteroids (ICS) controller therapy is a risk factor for greater asthma burden. ICS concomitantly used with rescue inhalers (Patient-Activated ...Reliever-Triggered ICS 'PARTICS') reduced asthma exacerbations in efficacy trials, but whether PARTICS is effective in pragmatic trials is unknown.
We conducted this pilot to determine the feasibility of executing a large-scale pragmatic PARTICS trial and to improve study protocols.
Four sites recruited 33 Hispanic or black adults with persistent asthma, randomized them approximately 3:1 to intervention or usual care, and followed them for 12 weeks. All participants received asthma guideline-based educational videos; intervention participants received video-based instructions on implementing PARTICS plus usual medications. The study involved 1 randomization visit and monthly questionnaires. Timely questionnaire responses (±2 weeks) were monitored. Participants underwent qualitative phone interviews to assess self-reported adherence to PARTICS and understand barriers to completing study procedures.
Timely questionnaire response rates were 61%, 64%, and 70% at 4, 8, and 12 weeks, respectively. Self-reported adherence to PARTICS was 76% (95% confidence interval CI, 58%-94% n = 21), 88% (95%CI, 72%-100% n = 16), and 62% (95%CI, 36%-88% n = 13) at weeks 1, 6, and 12, respectively. Barriers to completing study procedures included difficulties with questionnaire access, remembering to use ICS and rescue inhalers together, and obtaining refills. Only 22% of participants recognized their short-acting bronchodilator as "reliever" or "rescue."
Recruitment was feasible within the allocated period. Adherence to PARTICS was incomplete, questionnaire completion was suboptimal, and common rescue inhaler nomenclature usage was limited. We have modified the full study protocol to attempt to improve adherence to PARTICS and minimize barriers to study procedures.
pilot study for 'PeRson EmPowered Asthma Relief' (PREPARE, NCT02995733).
Asthma prevalence, morbidity, and mortality disproportionately impact African American/Black (AA/B) and Hispanic/Latinx (H/L) communities. Adherence to daily inhaled corticosteroid (ICS), recommended ...by asthma guidelines in all but the mildest cases of asthma, is generally poor. As-needed ICS has shown promise as a patient-empowering asthma management strategy, but it has not been rigorously studied in AA/B or H/L patients or in a real-world setting.
Design and Aim
The PeRson EmPowered Asthma RElief (PREPARE) Study is a randomized, open-label, pragmatic study which aims to assess whether a patient-guided, reliever-triggered ICS strategy called PARTICS (Patient-Activated Reliever-Triggered Inhaled CorticoSteroid) can improve asthma outcomes in AA/B and H/L adult patient populations. In designing and implementing the study, the PREPARE research team has relied heavily on advice from AA/B and H/L Patient Partners and other stakeholders.
Methods
PREPARE is enrolling 1200 adult participants (600 AA/Bs, 600H/Ls) with asthma. Participants are randomized to PARTICS + Usual Care (intervention) versus Usual Care (control). Following a single in-person enrollment visit, participants complete monthly questionnaires for 15 months. The primary endpoint is annualized asthma exacerbation rate. Secondary endpoints include asthma control; preference-based quality of life; and days lost from work, school, or usual activities.
Discussion
The PREPARE study features a pragmatic design allowing for the real-world assessment of a patient-centered, reliever-triggered ICS strategy in AA/B and H/L patients. Outcomes of this study have the potential to offer powerful evidence supporting PARTICS as an effective asthma management strategy in patient populations that suffer disproportionately from asthma morbidity and mortality.
Aims
Hypothesis 1 of the Surgical Treatment for Ischemic Heart Failure (STICH) trial enrolled 1212 patients with an LVEF of ≤35% and CAD amenable to coronary artery bypass grafting (CABG). Patients ...were randomized to CABG and optimal medical therapy (MED) or MED alone. The objective was to assess whether or not patients with diabetes mellitus (DM) enrolled in the STICH trial would have greater benefit from CABG than patients without DM.
Methods and results
The characteristics and clinical outcomes of patients with and without DM randomized to CABG and MED or MED alone were compared. DM was present in 40%. At baseline, patients with DM had more triple vessel CAD, higher LVEF, and smaller left ventricular volumes. In patients with DM, the primary outcome of all‐cause mortality occurred in 39% of patients in the MED group and 39% in the CABG group hazard ratio (HR) with CABG 0.96, 95% confidence interval (CI) 0.73–1.26. In patients without DM, the primary outcome occurred in 41% of patients in the MED group and 32% in the CABG group (HR with CABG 0.80, 95% CI 0.63–1.02). While numerically it would appear that the treatment effect of CABG is blunted in patients with DM, there was no significant interaction between DM and treatment group on formal statistical testing.
Conclusions
Patients with DM enrolled in the STICH trial had more triple vessel disease, smaller hearts, and higher LVEF than those without DM. CABG did not exert greater benefit in patients with DM.
Abstract only
Introduction:
Diabetes mellitus (DM), coronary artery disease (CAD) and heart failure commonly coexist. Hypothesis 1 of the Surgical Treatment for Ischemic Heart Failure (STICH) trial ...enrolled 1212 patients with a left ventricular ejection fraction (LVEF) of 35% or less and CAD amenable to CABG. Patients were randomised to CABG and optimal medical therapy (OMT) or OMT alone.
Hypothesis:
We assessed the hypothesis that patients with DM enrolled in the STICH trial would have greater benefit of CABG than patients without DM.
Methods:
We compared the characteristics and clinical outcomes of patients with and without DM randomized to CABG and OMT or OMT alone. Cox-proportional hazards analyses were used to assess treatment effect.
Results:
Diabetes was present in 40.3%. At baseline, patients with DM had more triple vessel CAD (66% v 57%, p<0.001), higher LVEF median 29% (IQR:22,35) vs 27% (IQR:22,33), p=0.015 and smaller left ventricular end diastolic volume index median 105 ml/m2 (IQR:85, 128) vs 117 ml/m2 (IQR:93, 146) (p<0.001). Among patients with DM, there was a higher proportion of females, higher BMI on average, worse renal function, and more hypertension. Patients with DM undergoing CABG spent longer on cardio-pulmonary bypass median 97 (IQR:71,126) vs 87 (IQR:65, 115) minutes, p=0.029, and were more likely to develop perioperative AF (23% vs 11%, p<0.001) and worsening renal function (9% vs 4%, p=0.021). Patients with DM on OMT had similar outcomes as those on OMT without diabetes (Table 1). A statistically significant or near statistically significant improvement in clinical outcomes with CABG compared to OMT was documented in patients without DM, but not in patients with DM. However, there was no significant interaction between DM and treatment group on formal statistical testing.
Conclusions:
Patients with and without DM enrolled in the STICH trial had similar outcomes at 5 years, and CABG did not exert greater benefit in patients with DM.
PDF
