It is unclear if clinician risk stratification has changed with time. The aim of this study was to assess the temporal change in the concordance between patient presenting risk and the intensity of ...evidence-based therapies received for non–ST-segment elevation acute coronary syndromes over a 9-year period. Data from 3,562 patients with non–ST-segment elevation acute coronary syndromes enrolled in the Australian and New Zealand population of the Global Registry of Acute Coronary Events (GRACE) from 1999 to 2007 were analyzed. Patients were stratified to risk groups on the basis of the GRACE risk score for in-hospital mortality. Main outcome measures included in-hospital use of widely accepted evidence-based medications, investigations, and procedures. Invasive management was consistently higher in low-risk patients than in intermediate- or high-risk patients (coronary angiography 66.7% vs 63.5% vs 35.3%, p <0.001; percutaneous coronary intervention 31.1% vs 22.0% vs 12.9%, p <0.001). Absolute rates of angiography and percutaneous coronary intervention in the high-risk group remained 24% and 15% lower compared to the low-risk group in the most recent time period (2005 to 2007). In-hospital use of thienopyridine, low–molecular weight heparin, and glycoprotein IIb/IIIa inhibitors showed a similar inverse relation with risk. Prescription of aspirin, β blockers, statins, and angiotensin receptor blockers was inversely related to risk before 2004, although this inverse relation was no longer present in the most recent time period (2005 to 2007). Only in-hospital use of unfractionated heparin showed use concordant with patient risk status. In conclusion, despite an overall increase in the uptake of evidence-based therapies, most investigations and treatments are not targeted on the basis of patient risk. Clinician risk stratification remains suboptimal compared to objective measures of patient risk.
Background Cardiac troponin (T and I) are considered the standard markers for detection of myocardial damage and the diagnosis of acute coronary syndrome (ACS) among patients who present to an ...emergency department with chest pain. However, these markers can be released in other situations and have significant impact on short- and long-term clinical outcomes. In this study, we examine late mortality rates among patients presenting with a suspected ACS due to an unstable coronary plaque and those patients having a non-ACS. Methods 4,388 patients were hospitalised with suspected ACS, between the 14th and 27th of May 2012 in the Australia and New Zealand SNAPSHOT ACS study. Those patients were categorised in five diagnostic groups: 1) ST elevation MI (n=419); 2) non-ST elevation MI (n=1012); 3) unstable angina (n=925); 4) non-ACS diagnoses (n=837); and 5) chest pain considered unlikely ischaemic (not otherwise specified, n=1195). Result The respective mortality rates at 18 months in these groups were 16.2%, 16.3%, 6.8%, 12.8%, and 4.8%; Pearson χ2 =110 p<0.001. Among non-ACS diagnoses patients (group 4) those with the highest mortality rates (cardiac (14.4%), respiratory (18.2%), sepsis (15.4%) and neoplastic (67%)) had the highest rates of elevated troponin levels (48%, 31%, 38% and 67% respectively). By contrast, those with the lowest mortality rates (musculoskeletal (2.9%), gastrointestinal disorders (3.9%) and non-specific chest pain (7.4%)) had the lowest rate of troponin levels (9%, 18% and 15.8% respectively). However, after adjusting for baseline clinical and demographic characteristics, the mortality rate at 18 months for patients with elevated troponin was similar for ACS or non-ACS diagnoses (Hazard Ratio, 95% C.I.0.98–1.07, P=0.333). Conclusions Among patients in the 2012 SNAPSHOT ACS study, non-ACS subgroups diagnoses characterised by high rates of elevated troponin levels had high mortality rates similar to those diagnosed with ACS. Therapies known to be effective in ACS patients, including early invasive management, should be examined in these non-ACS patients with troponin elevations within adequately powered randomised trials.
Background There is wide variation in the use of radial over femoral access for patients with ACS. This study evaluates the factors associated with the selection of radial versus femoral angiography ...in Australia and New Zealand and the effect of access site on clinical events in acute coronary syndrome (ACS) patients. Methods An analysis of the SNAPSHOT ACS audit was conducted during May 2012 across 286 hospitals in Australia and New Zealand. Data collected included baseline patient characteristics, hospital site details, treatment received, clinical events in-hospital and mortality at 18 months. Univariate and multivariable analyses were performed. Results Of the 1621 patients undergoing coronary angiography, access was through the femoral artery in 1043 (63%), and the radial in 578 (36%) patients. Radial access dominated in New Zealand (241 out of 327, 73.7%), compared to Australia (337 out of 1293, 26.1%, p=<0.001), with interstate variation (6% to 54%, p=<0.001). Independent predictors of access site included country of admission (Odds of radial, Aus v NZ OR 0.14, 95% CI 0.08-0.24, p=<0.0001), prior CABG surgery (OR 0.16, 95% CI 0.09-0.31, p=<0.0001), high GRACE score (90th decile) (OR 0.44, 95% CI 0.21-0.91, p=0.026) and admission to a centre with high annual PCI volume (>209 cases per year) (OR 1.86, 95% CI 1.06-3.26, p=0.03). After adjustment, there was no difference in clinical events in-hospital or mortality at 18 months Conclusion Coronary angiography in New Zealand rather than Australia is the strongest predictor of radial access in ACS patients. There was no difference in outcomes according to access site in this population based cohort study.
The study sought to assess the safety, feasibility, and effect of diltiazem as disease-modifying therapy for at-risk hypertrophic cardiomyopathy (HCM) mutation carriers.
HCM is caused by sarcomere ...mutations and characterized by left ventricular hypertrophy (LVH) with increased risk of heart failure and sudden death. HCM typically cannot be diagnosed early in life, although subtle phenotypes are present. Animal studies indicate that intracellular calcium handling is altered before LVH develops. Furthermore, early treatment with diltiazem appeared to attenuate disease emergence.
In a pilot, double-blind trial, we randomly assigned 38 sarcomere mutation carriers without LVH (mean 15.8 years of age) to therapy with diltiazem 360 mg/day (or 5 mg/kg/day) or placebo. Treatment duration ranged from 12 to 42 months (median 25 months). Study procedures included electrocardiography, echocardiography, cardiac magnetic resonance imaging, and serum biomarker measurement.
Diltiazem was not associated with serious adverse events. Heart rate and blood pressure did not differ significantly between groups. However, mean left ventricular (LV) end-diastolic diameter improved toward normal in the diltiazem group but decreased further in controls (change in z-scores, +0.6 vs. –0.5; p < 0.001). Mean LV thickness-to-dimension ratio was stable in the diltiazem group but increased in controls (–0.02 vs. +0.15; p = 0.04). Among MYBPC3 mutation carriers, LV wall thickness and mass, diastolic filling, and cardiac troponin I levels improved in those taking diltiazem compared with controls. Four participants developed overt HCM, 2 in each treatment group.
Pre-clinical administration of diltiazem is safe and may improve early LV remodeling in HCM. This novel strategy merits further exploration. (Treatment of Preclinical Hypertrophic Cardiomyopathy With Diltiazem; NCT00319982).
Summary Background Decreased systolic function is central to the pathogenesis of heart failure in millions of patients worldwide, but mechanism-related adverse effects restrict existing inotropic ...treatments. This study tested the hypothesis that omecamtiv mecarbil, a selective cardiac myosin activator, will augment cardiac function in human beings. Methods In this dose-escalating, crossover study, 34 healthy men received a 6-h double-blind intravenous infusion of omecamtiv mecarbil or placebo once a week for 4 weeks. Each sequence consisted of three ascending omecamtiv mecarbil doses (ranging from 0·005 to 1·0 mg/kg per h) with a placebo infusion randomised into the sequence. Vital signs, blood samples, electrocardiographs (ECGs), and echocardiograms were obtained before, during, and after each infusion. The primary aim was to establish maximum tolerated dose (the highest infusion rate tolerated by at least eight participants) and plasma concentrations of omecamtiv mecarbil; secondary aims were evaluation of pharmacodynamic and pharmacokinetic characteristics, safety, and tolerability. This study is registered at ClinicalTrials.gov , number NCT01380223. Findings The maximum tolerated dose of omecamtiv mecarbil was 0·5 mg/kg per h. Omecamtiv mecarbil infusion resulted in dose-related and concentration-related increases in systolic ejection time (mean increase from baseline at maximum tolerated dose, 85 SD 5 ms), the most sensitive indicator of drug effect ( r2 =0·99 by dose), associated with increases in stroke volume (15 2 mL), fractional shortening (8% 1), and ejection fraction (7% 1; all p<0·0001). Omecamtiv mecarbil increased atrial contractile function, and there were no clinically relevant changes in diastolic function. There were no clinically significant dose-related adverse effects on vital signs, serum chemistries, ECGs, or adverse events up to a dose of 0·625 mg/kg per h. The dose-limiting toxic effect was myocardial ischaemia due to excessive prolongation of systolic ejection time. Interpretation These first-in-man data show highly dose-dependent augmentation of left ventricular systolic function in response to omecamtiv mecarbil and support potential clinical use of the drug in patients with heart failure. Funding Cytokinetics Inc.
Background Return to work is an important indicator of recovery after acute cardiac events. This study aimed to determine rates of work resumption and identify predictors of non-return to work and ...delayed resumption of work. Methods 401 currently employed patients consecutively admitted after acute coronary syndrome or to undergo coronary artery bypass graft surgery were recruited. Patient characteristics, perceptions and occupational outcomes were investigated via interviews and self-report questionnaires. Results Twenty-three patients were lost to follow-up. Of the 378 completers, 343 (90.7%) patients resumed work, while 35 (9.3%) did not. By four months, 309 (91.1%) patients had returned to work. At 12 months, 302 (79.9%) of the 378 patients were employed, 32 (8.5%) unemployed and 20 (5.3%) retired. The employment status of 24 (6.3%) patients was unknown. Non-return to work was significantly more likely if patients were not intending to return to work or were uncertain, had a negative perception of health, had a comorbidity other than diabetes and reported financial stress. Significant predictors of delayed return to work were cardiac rehabilitation attendance, longer hospital stay, past angina, having a manual job, physically active work, job dissatisfaction, no confidante and depression. Conclusions Patients at risk of poor occupational outcomes can be identified early. Strategies to improve vocational rehabilitation require further investigation.
To determine childhood factors that predict attention-deficit/hyperactivity disorder (ADHD) persistence and desistence in adulthood.
Regression analyses were used to determine associations between ...childhood factors and adult ADHD symptom persistence in 453 participants (mean age, 25 years) from the Multimodal Treatment Study of Children with ADHD (MTA). Childhood IQ, total number of comorbidities, child-perceived parenting practices, child-perceived parent-child relationships, parental mental health problems, marital problems of parents, household income levels, and parental education were assessed at a mean age of 8 years in all participants. Adult ADHD persistence was defined using DSM-5 symptom counts either with or without impairment, as well as mean ADHD symptom scores on the Conners' Adult ADHD Rating Scale (CAARS). Age, sex, MTA site, and childhood ADHD symptoms were covaried.
The most important childhood predictors of adult ADHD symptom persistence were initial ADHD symptom severity (odds ratio OR = 1.89, standard error SE = 0.28, p = .025), comorbidities (OR = 1.19, SE = 0.07, p = .018), and parental mental health problems (OR = 1.30, SE = 0.09, p = .003). Childhood IQ, socioeconomic status, parental education, and parent-child relationships showed no associations with adult ADHD symptom persistence.
Initial ADHD symptom severity, parental mental health, and childhood comorbidity affect persistence of ADHD symptoms into adulthood. Addressing these areas early may assist in reducing adult ADHD persistence and functioning problems.
No periprocedural metric has demonstrated improved cardiac resynchronization therapy (CRT) outcomes in a multicenter setting.
We sought to determine if left ventricular (LV) lead placement targeted ...to the coronary sinus (CS) branch generating the best acute hemodynamic response (AHR) results in improved outcomes at 6 months.
In this multicenter randomized controlled trial, patients were randomized to guided CRT or conventional CRT. Patients in the guided arm had LV dP/dtmax measured during biventricular (BIV) pacing. Target CS branches were identified and the final LV lead position was the branch with the best AHR and acceptable threshold values. The primary endpoint was the proportion of patients with a reduction in LV end-systolic volume (LVESV) of ≥15% at 6 months.
A total of 281 patients were recruited across 12 centers. Mean age was 70.8 ± 10.9 years and 54% had ischemic etiology. Seventy-three percent of patients in the guided arm demonstrated a reduction in LVESV of ≥15% at 6 months vs 60% in the conventional arm (P = .02). Patients with AHR ≥ 10% were more likely to demonstrate a reduction of ESV ≥ 15% (84% of patients with an AHR ≥10% vs 28% with an AHR <10%; P < 0.001). Procedure duration and fluoroscopy times were longer in the pressure wire–guided arm (104 ± 39 minutes vs 142 ± 39 minutes; P < .001 and 20 ±16 minutes vs 28 ± 15 minutes; P = .002).
AHR determined by invasively measuring LV dP/dtmax during BIV pacing predicts reverse remodeling 6 months after CRT. Patients in whom LV dP/dtmax was used to guide LV lead placement demonstrated better rates of reverse remodeling.
Yet, more people die each year of CVD than from any other single cause: CVD causes 30% of deaths any given year, more than all infectious and parasitic diseases combined (2). ...CVD is a significant ...cause of premature death and the primary driver of morbidity for all NCDs, the largest burden of which occurs in low- and middle-income countries. ...we want to ensure that the World Health Organization's "25x25" targets regarding risk factors are included in all national plans, an area around which the World Heart Federation and its members are focusing resources and attention. ...we support the proposed SDG health goal as the overarching goal to achieve these results: "Ensure healthy lives and promote wellbeing for all at all ages."
Background Many patients provisionally diagnosed with acute myocardial infarction (AMI) have angiographically unobstructed coronary arteries. Despite other potential causes, patients are often ...diagnosed as AMI with psychosocial implications and medication burden. The aim of this audit was to review such patients at our centre. Methods All patients investigated for possible AMI with coronary angiography from 2007 until 2011 at Christchurch Hospital, New Zealand, in whom cardiac troponin was elevated (with no other cause found for that elevation) but coronary angiography showed diameter stenosis <50% were reviewed. Primary outcome was two-year cardiac death and AMI (by universal definition). Results Of the 351/6493 (5.4%) who met the inclusion criteria, 180 had normal angiograms and 171 had non-obstructive coronary disease (stenosis >0% and <50%). By two years there were two cardiac deaths (0.6%) and five AMIs (1.4%). The primary outcome rate was therefore 2.0% (2.2% for those with normal angiograms and 1.8% with non-flow limiting coronary disease, p=1.000). Conclusion Patients who have presented with AMI symptoms, elevated cardiac troponin, and unobstructed coronary arteries on angiography are at very low risk of cardiac death (0.6%), AMI (1.4%) or either (2.0%) at two-year follow-up.
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