G. Devlin

The Singapore Heart Failure Outcomes and Phenotypes (SHOP) Study and Prospective Evaluation of Outcome in Patients With Heart Failure With Preserved Left Ventricular Ejection Fraction (PEOPLE) Study: Rationale and Design

BACKGROUND Heart failure (HF) with preserved ejection fraction (EF) accounts for a substantial proportion of cases of HF, and to date no treatments have clearly improved outcome. There are also little data comparing HF cohorts of differing ethnicity within the Asia-Pacific region. METHODS The Singapore Heart Failure Outcomes and Phenotypes (SHOP) study and Prospective Evaluation of Outcome in Patients with Heart Failure with Preserved Left Ventricular Ejection Fraction (PEOPLE) study are parallel prospective studies using identical protocols to enroll patients with HF across 6 centers in Singapore and 4 in New Zealand. The objectives are to determine the relative prevalence, characteristics, and outcomes of patients with HF and preserved EF (EF ≥50%) compared with those with HF and reduced EF, and to determine initial data on ethnic differences within and between New Zealand and Singapore. Case subjects (n = 2,500) are patients hospitalized with a primary diagnosis of HF or attending outpatient clinics for management of HF within 6 months of HF decompensation. Control subjects are age- and gender-matched community-based adults without HF from Singapore (n = 1,250) and New Zealand (n = 1,073). All participants undergo detailed clinical assessment, echocardiography, and blood biomarker measurements at baseline, 6 weeks, and 6 months, and are followed over 2 years for death or hospitalization. Substudies include vascular assessment, cardiopulmonary exercise testing, retinal imaging, and cardiac magnetic resonance imaging. CONCLUSIONS The SHOP and PEOPLE studies are the first prospective multicenter studies defining the epidemiology and interethnic differences among patients with HF in the Asia-Oceanic region, and will provide unique insights into the pathophysiology and outcomes for these patients.

Management and outcomes of lower risk patients presenting with acute coronary syndromes in a multinational observational registry

Objective: To document patterns of risk stratification, management practices, and outcomes among patients with acute coronary syndromes (ACS) presenting without high risk features. Patients: The study was based on 11 885 consecutive patients presenting with non-ST segment elevation ACS enrolled in GRACE (global registry of acute coronary events). Patients without dynamic ST segment changes, positive troponin (or other cardiac markers), or haemodynamic or arrhythmic instability were defined as being at lower risk. Main outcome measures: Management and outcomes were compared with high risk presentations. Results: Of 11 885 patients presenting with unstable angina or non-ST segment elevation myocardial infarction, 4252 (36%) were regarded as being at lower risk. Functional testing for risk stratification was performed in 1163 of 4207 (28%) lower risk and 1531 of 7521 (20%) high risk patients (p < 0.0001). Coronary angiography was performed in 1930 of 4190 (46%) and 3860 of 7544 (51%), and echocardiography in 1692 of 4190 (40%) and 4348 of 7533 (58%) of lower risk and high risk patients, respectively (p < 0.0001 for both). Over one third of patients did not undergo further risk assessment with angiography or functional testing (2746 of 7437 (37%) high risk, 1499 of 4148 (36%) lower risk, not significant). Death occurring in hospital was more likely in the high risk cohort (41 of 4227 (1.0%) lower risk v 215 of 7586 (2.8%) high risk, p < 0.0001), whereas rates of recurrent angina during admission and readmission were similar in both groups (1354 of 4231 (32%) high risk, 2313 of 7587 (31%) lower risk, not significant). In the six months after discharge, death or myocardial infarction occurred in 79 of 3223 (2.5%) lower risk patients and 302 of 5451 (5.5%) high risk patients (p < 0.0001). Conclusions: Globally, further risk stratification after ACS presentation is suboptimal, regardless of presenting characteristics. Although in-hospital death and myocardial infarction are uncommon, recurrent ischaemia is encountered often in both groups. It remains to be seen whether better outcomes may be achieved with wider application of risk stratification and appropriately directed management strategies.

Transcatheter Aortic Valve Implantation Complicated By Acute Structural Valve Failure Requiring Immediate Valve In Valve Implantation

The first percutaneous transcatheter aortic valve implantation (TAVI) was performed in 2002 by Alain Cribier with over 10,000 valve implants since. Despite this, as with all new technologies we remain on a learning curve and continue to encounter new challenges and complications. We report a case of acute structural valve failure treated successfully with a second valve in valve implantation of transcatheter aortic valve in a patient who had severe aortic stenosis (AS) complicated by a severely unfolded aorta.

Mortality associated with heart failure with preserved vs. reduced ejection fraction in a prospective international multi-ethnic cohort study

Aims Whether prevalence and mortality of patients with heart failure with preserved or mid-range (40-49%) ejection fraction (HFpEF and HFmREF) are similar to those of heart failure with reduced ejection fraction (HFrEF), as reported in some epidemiologic studies, remains highly controversial. We determined and compared characteristics and outcomes for patients with HFpEF, HFmREF, and HFrEF in a prospective, international, multi-ethnic population. Methods and results Prospective multi-centre longitudinal study in New Zealand (NZ) and Singapore. Patients with HF were assessed at baseline and followed over 2 years. The primary outcome was death from any cause. Secondary outcome was death and HF hospitalization. Cox proportional hazards models were used to compare outcomes for patients with HFpEF, HFmrEF, and HFrEF. Of 2039 patients enrolled, 28% had HFpEF, 13% HFmrEF, and 59% HFrEF. Compared with HFrEF, patients with HFpEF were older (62 vs. 72 years), more commonly female (17% vs. 48%), and more likely to have a history of hypertension (61% vs. 78%) but less likely to have coronary artery disease (55% vs. 41%). During 2 years of follow-up, 343 (17%) patients died. Adjusting for age, sex, and clinical risk factors, patients with HFpEF had a lower risk of death compared with those with HFrEF (hazard ratio 0.62, 95% confidence interval 0.46-0.85). Plasma (NT-proBNP) was similarly related to mortality in both HFpEF, HFmrEF, and HFrEF independent of the co-variates listed and of ejection fraction. Results were similar for the composite endpoint of death or HF and were consistent between Singapore and NZ. Conclusion These prospective multinational data showed that the prevalence of HFpEF within the HF population was lower than HFrEF. Death rate was comparable in HFpEF and HFmrEF and lower than in HFrEF. Plasma levels of NT-proBNP were independently and similarly predictive of death in the three HF phenotypes. Trial Registration Australian New Zealand Clinical Trial Registry (ACTRN12610000374066).

Performance of the GRACE scores in a New Zealand acute coronary syndrome cohort

Background Risk stratification after acute coronary syndrome (ACS) event is recommended to guide intensity and timing of investigation and management. The Global Registry of Acute Coronary Events (GRACE) investigators have published several scores for predicting patient risk both at hospital admission and discharge. Objective To evaluate the performance of the admission-to-6-month and discharge-to-6-month GRACE scores for predicting myocardial infarction (MI) and mortality in a contemporary cohort of patients admitted with ACS. Methods The cohort comprised 3743 consecutive patients admitted to cardiology services in two large New Zealand hospitals with an ACS between 2007 and 2011. Risk score data was collected in an electronic registry and linked anonymously to national hospitalisation and mortality records. Results Between admission and 6 months, 160 patients died and another 269 were rehospitalised with an MI. The GRACE admission-to-6-month total mortality and mortality/MI scores both overestimated event rates approximately twofold. The discharge-to-6-month mortality equation was better calibrated. Global discrimination was very good for both admission-to-6-month and discharge-to-6-month mortality scores (c=0.805 and c=0.795, respectively) and moderately good for the corresponding mortality/MI equations (c=0.652 and c=0.624, respectively). Conclusions In a contemporary ACS cohort, the GRACE discharge-to-6-month mortality score has very good discrimination and accurately predicts mortality rates, whereas the admission-to-6-month equation, despite good discrimination, overestimated risk. Recalibration or more dynamic modelling of inhospital risk which includes variables such as time from admission to risk assessment are needed to support use of ACS risk assessment inhospital.

Chest Pain Unit (CPU) in the Management of Low to Intermediate Risk Acute Coronary Syndrome: A Tertiary Hospital Experience from New Zealand

BACKGROUND A chest pain unit (CPU) for management of patients with chest pain at low to intermediate risk for acute coronary syndrome (ACS) appears safe and cost-effective. We report our experience with a CPU from March 2005 to July 2009. METHODS Prospective audit of patients presenting with chest pain suggestive of ACS but no high risk features and managed using a CPU, which included; serial cardiac troponins and electrocardiography and exercise tolerance test (ETT) if indicated. Outcomes assessed included three-month readmission rate and one year mortality. RESULTS 2358 patients were managed according to the CPU. Mean age 56 years (17-96 years), 59% men and median stay of 22h (IQR 17-26h). 1933 (82%) were diagnosed as non-cardiac chest pain. 1741 (74%) patients had an ETT. Median time from triage to ETT was 21h (IQR 16-24h). 64 (2.7%) were readmitted within three months. The majority of readmissions, 39 (61%) were for a non-cardiac cause. Twenty patients (1%) were readmitted with ACS. There was no cardiac death after one year of being discharged as non-cardiac chest pain. CONCLUSIONS This study confirms that a CPU with high usage of predischarge ETT is a safe and effective way of excluding ACS in patients without high risk features in a New Zealand setting.

Long-term mortality after primary percutaneous coronary intervention for high-risk myocardial infarction.

BACKGROUND Primary percutaneous coronary intervention (PPCI) has evolved, including the introduction of stents and platelet glycoprotein IIb/IIIa receptor inhibitors (GPI). The effects of these changes and other variables on long-term survival for a single-centre service were studied. METHODS A prospective database of clinical and angiographic variables were kept for patients treated with PPCI in Waikato Hospital from 1996 to 2006 (n=527). This was analysed with long-term mortality data. Survival was recorded using Kaplan-Meier curves. Multivariate analysis of factors at presentation, including ethnicity was performed. RESULTS 5, 8 & 10-year survival rates were 76.5% (n=274), 72.7% (n=125) & 71.0% (n=19) respectively. Increased stent (42.8% vs. 84.1%, p<0.001) and GPI (39.6% vs. 73.3%, p<0.001) use was seen between early and late stages of the study. Stent use was associated with greater 5-year survival (80.5% vs. 70.8%, p=0.02), but GPI use was not. Multivariate analysis showed stent use independently predicted reduced mortality. Age, Maori ethnicity, renal failure and cardiogenic shock predicted higher mortality. CONCLUSIONS Survival after PPCI remains high long-term. Stent and GPI use significantly increased. Stent, but not GPI, use was associated with improved survival. Maori ethnicity was under-represented in the study and is associated with worse long-term outcomes after myocardial infarction (MI).

All-Cause Mortality Following an Acute Coronary Syndrome: 12-Year Follow-Up of the Comprehensive 2002 New Zealand Acute Coronary Syndrome Audit

BACKGROUND To describe the long-term mortality of a complete national cohort of acute coronary syndrome (ACS) patients enrolled in 2002, to compare this with a national age, sex and Māori ethnicity matched population, and to assess the influence of baseline factors on the 12-year mortality. METHODS We reviewed 721 patients with a discharge diagnosis of an ACS who were enrolled in the first New Zealand ACS audit group cohort over 14days in May 2002. We matched the cohort to the national mortality database using each patients unique national identity number. RESULTS Over a median follow-up of 12.7 years of 721 patients discharged with an ACS, overall mortality was 52%: ST-elevation myocardial infarction (STEMI) (58%), non-ST-elevation myocardial infarction (NSTEMI) (61%) and unstable angina pectoris (UAP) (42%) patients, p<0.0001. In an age-adjusted survival model, males had a 29% increased mortality rate compared to females with a hazard ratio of 1.29 (95% CI 1.04, 1.61, p=0.019). Over 12 years there were 339 (47%) deaths, compared to 284 (39%) deaths observed in the matched population. The standardised mortality ratio for patients admitted with an ACS in New Zealand is 1.3 (95% CI 1.2, 1.5) with eight patients per 100 not surviving to 12 years compared to this matched population. CONCLUSIONS The high mortality rate in this ACS cohort is a stark reminder of the prognostic implications of a presentation with an ACS. It emphasises the on-going need for optimal management of these patients throughout every stage of their initial treatment and subsequent on-going care.

A Comparison of Radial and Femoral Coronary Angiography in Patients From SNAPSHOT ACS, a Prospective Acute Coronary Syndrome Audit in Australia and New Zealand.

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.