Guideline-indicated treatments and diagnostics, GRACE risk score, and survival for non-ST elevation myocardial infarction.

Aims: To investigate whether improved survival from non-ST-elevation myocardial infarction (NSTEMI), according to GRACE risk score, was associated with guideline-indicated treatments and diagnostics, and persisted after hospital discharge. Methods and results: National cohort study (n = 389 507 patients, n = 232 hospitals, MINAP registry), 2003-2013. The primary outcome was adjusted all-cause survival estimated using flexible parametric survival modelling with time-varying covariates. Optimal care was defined as the receipt of all eligible treatments and was inversely related to risk status (defined by the GRACE risk score): 25.6% in low, 18.6% in intermediate, and 11.5% in high-risk NSTEMI. At 30 days, the use of optimal care was associated with improved survival among high [adjusted hazard ratio (aHR) -0.66 95% confidence interval (CI) 0.53-0.86, difference in absolute mortality rate (AMR) per 100 patients (AMR/100-0.19 95% CI -0.29 to -0.08)], and intermediate (aHR = 0.74, 95% CI 0.62-0.92; AMR/100 = -0.15, 95% CI -0.23 to -0.08) risk NSTEMI. At the end of follow-up (8.4 years, median 2.3 years), the significant association between the use of all eligible guideline-indicated treatments and improved survival remained only for high-risk NSTEMI (aHR = 0.66, 95% CI 0.50-0.96; AMR/100 = -0.03, 95% CI -0.06 to -0.01). For low-risk NSTEMI, there was no association between the use of optimal care and improved survival at 30 days (aHR = 0.92, 95% CI 0.69-1.38) and at 8.4 years (aHR = 0.71, 95% CI 0.39-3.74). Conclusion: Optimal use of guideline-indicated care for NSTEMI was associated with greater survival gains with increasing GRACE risk, but its use decreased with increasing GRACE risk.

Impact of hospital proportion and volume on primary percutaneous coronary intervention performance in England and Wales.

AIMS: To quantify the determinants of primary percutaneous coronary intervention (PCI) performance in England and Wales between 2004 and 2007. METHODS AND RESULTS: All 8653 primary PCI cases admitted to acute hospitals in England and Wales as recorded in the Myocardial Ischaemia National Audit Project (MINAP) 2004-2007. We studied the impact of the volume of primary PCI cases (hospital volume) on door-to-balloon (DTB) times and the proportion of patients treated with primary PCI (hospital proportion) on 30-day mortality and employed regression analysis to identify reasons for DTB time variations with a multilevel component to express hospital variation. The proportion of patients receiving primary PCI increased from 5% in 2004 to 20% in 2007. Median DTB times reduced from 84 min in 2004 to 61 min in 2007. Median DTB times decreased as the number of primary PCI procedures increased. The 30-day all-cause mortality rate for hospitals performing primary PCI on >25% of ST-elevation myocardial infarction patients [5.0%; 95% confidence interval (CI): 3.9-6.1%] was almost double that of hospitals performing primary PCI on more than 75% (2.7%; 95% CI: 2.0-3.5%). Time-of-day, year of admission, sex, and diabetes significantly influenced DTB times. Hospital variation was evident by a hospital-level DTB time standard deviation of 12 min. CONCLUSIONS: There was a large variation in DTB times between the best and worst performing hospitals. Although patient-related factors impacted upon DTB times, the volume and proportion of patients undergoing primary PCI were significantly associated with delay and early mortality-hospitals with the highest proportion of primary PCI had the lowest mortality.

A nationwide causal mediation analysis of survival following ST-elevation myocardial infarction.

OBJECTIVE: International studies report a decline in mortality following ST-elevation myocardial infarction (STEMI). The extent to which the observed improvements in STEMI survival are explained by temporal changes in patient characteristics and utilisation of treatments is unknown. METHODS: Cohort study using national registry data from the Myocardial Ischaemia National Audit Project between first January 2004 and 30th June 2013. 232 353 survivors of hospitalisation with STEMI as recorded in 247 hospitals in England and Wales. Flexible parametric survival modelling and causal mediation analysis were used to estimate the relative contribution of temporal changes in treatments and patient characteristics on improved STEMI survival. RESULTS: Over the study period, unadjusted survival at 6 months and 1 year improved by 0.9% and 1.0% on average per year (HR: 0.991, 95% CI: 0.988 to 0.994 and HR: 0.990, 95% CI: 0.987 to 0.993, respectively). The uptake of primary percutaneous coronary intervention (PCI) (HR: 1.025, 95% CI: 1.021 to 1.028) and increased prescription of P2Y12 inhibitors (HR: 1.035, 95% CI: 1.031 to 1.039) were significantly associated with improvements in 1-year survival. Primary PCI explained 16.8% (95% CI: 10.8% to 31.6%) and 13.2% (9.2% to 21.9%) of the temporal survival improvements at 6 months and 1 year, respectively, whereas P2Y12 inhibitor prescription explained 5.3% (3.6% to 8.8%) of the temporal improvements at 6 months but not at 1 year. CONCLUSIONS: For STEMI in England and Wales, improvements in survival between 2004 and 2013 were significantly explained by the uptake of primary PCI and increased use of P2Y12 inhibitors at 6 months and primary PCI only at 1 year. TRIAL REGISTRATION NUMBER: NCT03749694.

Predicting death due to progressive heart failure in patients with mild-to-moderate chronic heart failure.

OBJECTIVES: The aim of this study was to explore the value of noninvasive predictors of death/mode of death in ambulant outpatients with chronic heart failure (HF). BACKGROUND: Mortality in chronic HF remains high, with a significant number of patients dying of progressive disease. Identification of these patients is important. METHODS: We recruited 553 ambulant outpatients age 63 +/- 10 years with symptoms of chronic HF (New York Heart Association functional class, 2.3 +/- 0.5) and objective evidence of left ventricular dysfunction (ejection fraction <45%, cardiothoracic ratio >0.55, or pulmonary edema on chest radiograph). After 2,365 patient-years of follow-up, 201 patients had died, with 76 events due to progressive HF. RESULTS: Independent predictors of all-cause mortality assessed with the Cox proportional hazards model were as follows: a low standard deviation of all normal-to-normal RR intervals (SDNN); lower serum sodium and higher creatinine levels; higher cardiothoracic ratio; nonsustained ventricular tachycardia; higher left ventricular end-systolic diameter; left ventricular hypertrophy; and increasing age. Independent predictors of death specific to progressive HF were SDNN, serum sodium and creatinine levels. The hazard ratio of progressive HF death for a 10% decrease in SDNN was 1.06 (95% confidence interval [CI], 1.01 to 1.12); for a 2 mmol/l decrease in serum sodium, 1.22 (95% CI, 1.08 to 1.38); and for a 10 micromol/l increase in serum creatinine, 1.14 (95% CI, 1.09 to 1.19) (all p < 0.01). CONCLUSIONS: In ambulant outpatients with chronic HF, low serum sodium and SDNN and high serum creatinine identify patients at increased risk of death due to progressive HF.

A prognostic index to predict long-term mortality in patients with mild to moderate chronic heart failure stabilised on angiotensin converting enzyme inhibitors.

BACKGROUND: Mortality in patients with mild to moderate chronic heart failure remains high. At present there is no easy way of identifying patients within this population at increased risk of death in the medium to long term. AIMS: To develop a prognostic index to identify outpatients with mild to moderate chronic heart failure at increased risk of death. METHODS AND RESULTS: Five hundred and fifty-three outpatients mean (S.D.) age 63(+/-10) years with symptoms of chronic heart failure (mean New York Heart Association functional class, 2.3(+/-0.5)), were recruited between December 1993 and April 1995. By April 2000, 201 patients had died. Using data from non-invasive measurements of cardiac size, electrical and autonomic function, renal function and plasma biochemistry we identified eight independent predictors of mortality (all P<0.01). To develop a prognostic index, predictors were dichotomised by group median and awarded 0 or 1 point accordingly. Serum sodium /=111 micromol/l (1 point), cardiothoracic ratio >/=0.52 (1 point), SDNN /=487 ms (1 point), QRS dispersion>/=42.7 ms (1 point), the presence of non-sustained ventricular tachycardia (1 point) and voltage criteria for left ventricular hypertrophy on 12-lead ECG (1 point). We calculated risk scores for patients by adding the points of each independent risk factor. In the low-risk group (0-3 points) mortality at 5 years was 20% and in the high-risk group (4-8 points) 53%. The area under the receiver-operator characteristic curve using dichotomised variables was 0.74 and for continuous model 0.78. CONCLUSIONS: Our prognostic index which uses eight non-invasive measurements and a straightforward additive points system, has good discrimination and stratifies outpatients with chronic heart failure into high and low risk. This index may be useful in clinical care and risk stratification.

Acute coronary syndromes: an old age problem.

The increasing population in older age will lead to greater numbers of them presenting with acute coronary syndromes (ACS). This has implications on global healthcare resources and necessitates better management and selection for evidenced-based therapies. The elderly are a high risk group with more significant treatment benefits than younger ACS. Nevertheless, age related inequalities in ACS care are recognised and persist. This discrepancy in care, to some extent, is explained by the higher frequency of atypical and delayed presentations in the elderly, and less diagnostic electrocardiograms at presentation, potentiating a delay in ACS diagnosis. Under estimation of mortality risk in the elderly due to limited consideration for physiological frailty, co-morbidity, cognitive/psychological impairment and physical disability, less input by cardiology specialists and lack of randomised, controlled trials data to guide management in the elderly may further confound the inequality of care. While these inequalities exist, there remains a substantial opportunity to improve age related ACS outcomes. The selection of elderly patients for specific therapies and medication regimens are unanswered. There is a growing need for randomised, controlled trial data to be more representative of the population and enroll those of advanced age with co-morbidity. A lack of reporting of adverse events, such as renal impairment post coronary angiography, in the elderly further limit risk benefit decisions. Substantial improvements in care of elderly ACS patients are required and should be advocated. Ultimately, these improvements are likely to lead to better outcomes post ACS. However, the improvement in outcome is not infinite and will be limited by non-modifiable factors of age-related risk.

An assessment of the concentration-related prognostic value of cardiac troponin I following acute coronary syndrome.

In 2004 the British Cardiac Society redefined myocardial infarction by cardiac troponin I (cTnI) concentration: ≤ 0.06 µg/L (unstable angina), >0.06 to < 0.5 µg/L (myocardial necrosis), and ≥ 0.5 µg/L (myocardial infarction). We investigated the effects of this classification on all-cause mortality in 1,285 patients from the Evaluation of the Methods and Management of Acute Coronary Events (EMMACE)-2 registry. There were 528 deaths (6.6-year all-cause mortality 41.1%). Survival was greatest in the cTnI ≤ 0.06-µg/L subgroup at 30 days (p = 0.005), 6 months (p = 0.015), 1 year (p = 0.002), and 6.6 years (p = 0.045). After adjustment there was no significant difference in survival between the cTnI >0.06- to < 0.5-µg/L and ≥ 0.5-µg/L subgroups. Increased mortality (hazard ratio, 95% confidence interval) was associated with ages 70 to 80 years (2.58, 1.17 to 3.91) and >80 years (3.30, 3.50 to 5.06), peripheral vascular disease (1.50, 1.16 to 1.94), heart failure (1.36, 1.05 to 1.83), diabetes mellitus (1.68, 1.36 to 2.07), severe left ventricular systolic dysfunction (1.50, 1.00 to 2.21), and creatinine per 10 µmol/L (1.65, 1.02 to 1.08), whereas ages 50 to 60 years (0.55, 0.32 to 0.96), ß blockers (0.53, 0.44 to 0.64), aspirin (0.80 0.65 to 0.99), angiotensin-converting enzyme inhibitors (0.67, 0.56 to 0.80), statins (0.73, 0.59 to 0.90), and revascularization (0.33, 0.12 to 0.92) were associated with a lower risk of death. In conclusion, although quantitative evaluation of cTnI concentration in patients with acute coronary syndrome with cTnI > 0.06 µg/L was associated with no added prognostic information, the dichotomization of patients by cTnI status ("positive" and "negative") facilitates acute coronary syndrome risk stratification.