Robert J. Sapsford

Poor prognosis of patients presenting with symptomatic myocardial infarction but without chest pain

OBJECTIVE To describe the clinical features, prognosis, and treatment of patients presenting with atypical forms of acute myocardial infarction. DESIGN Consecutive cases of possible acute myocardial infarction were sought from coronary care registers, biochemistry records, and hospital management systems. Case notes were reviewed and predefined epidemiological and clinical variables were abstracted. SETTING 20 adjacent hospitals in the former Yorkshire region. PATIENTS 3684 consecutive cases of possible acute myocardial infarction admitted in a three month period were identified, of whom 2096 had a first episode of confirmed acute myocardial infarction. RESULTS 20.2% of all patients admitted with an eventual diagnosis of acute myocardial infarction presented with symptoms other than chest pain. Compared with the group presenting with chest pain, these patients were older (76.6v 69.1 years, p < 0.001), were more often women (54.6% v 35.3%, p < 0.001), and were more likely to have a history of heart failure (18.6%v 6.9%, p < 0.001). They had a higher 30 and 365 day mortality (49.2% and 61.0%, respectively) compared with patients presenting with chest pain (17.9% and 26.2%). In a Cox regression analysis the hazard ratio for presentation without chest pain was 1.60 (95% confidence interval 1.30 to 1.97) (p < 0.001) adjusted for age, heart rate, blood pressure, left ventricular impairment, and infarction with ST segment elevation as covariates. Importantly, they were also less likely to receive treatments with a proven ability to improve prognosis. CONCLUSIONS Atypical presentation of myocardial infarction without chest pain is common and associated with increased mortality. This may result in part from a failure to use beneficial treatment strategies.

Diabetes mellitus is associated with adverse prognosis in chronic heart failure of ischaemic and non-ischaemic aetiology

Background: It is unclear whether diabetes mellitus (DM) is an adverse prognostic factor in chronic heart failure (CHF) of ischaemic and non-ischaemic aetiology managed with contemporary evidence-based care. Methods: In total, 1091 outpatients with CHF with reduced ejection fraction were prospectively observed for a mean of 960 days. Total and cardiovascular mortality was quantified after accounting for potential confounders. Results: In total, 25.7% of patients had DM; this group was more likely to have CHF of ischaemic aetiology and was more symptomatic. Patients with DM received comparable medical- and device-based therapies, except for greater doses of loop diuretic. DM was associated with approximately doubled crude and adjusted risk of total and cardiovascular mortality. The association of diabetes with these outcomes in patients with ischaemic and non-ischaemic cardiomyopathies was of similar magnitude. Conclusions: In spite of advances in the management of CHF, DM remains a major adverse prognostic feature, irrespective of ischaemic/non-ischaemic aetiology.

Changing Characteristics and Mode of Death Associated With Chronic Heart Failure Caused by Left Ventricular Systolic Dysfunction A Study Across Therapeutic Eras

Background—Therapies for patients with chronic heart failure caused by left ventricular systolic dysfunction have advanced substantially over recent decades. The cumulative effect of these therapies on mortality, mode of death, symptoms, and clinical characteristics has yet to be defined. Methods and Results—This study was a comparison of 2 prospective cohort studies of outpatients with chronic heart failure caused by left ventricular systolic dysfunction performed between 1993 and 1995 (historic cohort: n=281) and 2006 and 2009 (contemporary cohort: n=357). In the historic cohort, 83% were prescribed angiotensin-converting enzyme inhibitors and 8.5% were prescribed &bgr;-adrenoceptor antagonists, compared with 89% and 80%, respectively, in the contemporary cohort. Mortality rates over the first year of follow-up declined from 12.5% to 7.8% between eras (P=0.04), and sudden death contributed less to contemporary mortality (33.6% versus 12.7%; P<0.001). New York Heart Association class declined between eras (P<0.001). QTc dispersion across the chest leads declined from 85 ms (SD, 2) to 34 ms (SD, 1) and left ventricular end-diastolic dimensions declined from 65 mm (SD, 0.6) to 59 mm (SD, 0.5) (both P<0.001). Conclusions—Survival has significantly improved in patients with chronic heart failure caused by left ventricular systolic dysfunction over the past 15 years; furthermore, sudden death makes a much smaller contribution to mortality, and noncardiac mortality is a correspondingly greater contribution. This has been accompanied by an improvement in symptoms and some markers of adverse electric and structural left ventricular remodeling.

Association of Postoperative High-Sensitivity Troponin Levels With Myocardial Injury and 30-Day Mortality Among Patients Undergoing Noncardiac Surgery

Importance Little is known about the relationship between perioperative high-sensitivity troponin T (hsTnT) measurements and 30-day mortality and myocardial injury after noncardiac surgery (MINS). Objective To determine the association between perioperative hsTnT measurements and 30-day mortality and potential diagnostic criteria for MINS (ie, myocardial injury due to ischemia associated with 30-day mortality). Design, Setting, and Participants Prospective cohort study of patients aged 45 years or older who underwent inpatient noncardiac surgery and had a postoperative hsTnT measurement. Starting in October 2008, participants were recruited at 23 centers in 13 countries; follow-up finished in December 2013. Exposures Patients had hsTnT measurements 6 to 12 hours after surgery and daily for 3 days; 40.4% had a preoperative hsTnT measurement. Main Outcomes and Measures A modified Mazumdar approach (an iterative process) was used to determine if there were hsTnT thresholds associated with risk of death and had an adjusted hazard ratio (HR) of 3.0 or higher and a risk of 30-day mortality of 3% or higher. To determine potential diagnostic criteria for MINS, regression analyses ascertained if postoperative hsTnT elevations required an ischemic feature (eg, ischemic symptom or electrocardiography finding) to be associated with 30-day mortality. Results Among 21 842 participants, the mean age was 63.1 (SD, 10.7) years and 49.1% were female. Death within 30 days after surgery occurred in 266 patients (1.2%; 95% CI, 1.1%-1.4%). Multivariable analysis demonstrated that compared with the reference group (peak hsTnT <5 ng/L), peak postoperative hsTnT levels of 20 to less than 65 ng/L, 65 to less than 1000 ng/L, and 1000 ng/L or higher had 30-day mortality rates of 3.0% (123/4049; 95% CI, 2.6%-3.6%), 9.1% (102/1118; 95% CI, 7.6%-11.0%), and 29.6% (16/54; 95% CI, 19.1%-42.8%), with corresponding adjusted HRs of 23.63 (95% CI, 10.32-54.09), 70.34 (95% CI, 30.60-161.71), and 227.01 (95% CI, 87.35-589.92), respectively. An absolute hsTnT change of 5 ng/L or higher was associated with an increased risk of 30-day mortality (adjusted HR, 4.69; 95% CI, 3.52-6.25). An elevated postoperative hsTnT (ie, 20 to <65 ng/L with an absolute change ≥5 ng/L or hsTnT ≥65 ng/L) without an ischemic feature was associated with 30-day mortality (adjusted HR, 3.20; 95% CI, 2.37-4.32). Among the 3904 patients (17.9%; 95% CI, 17.4%-18.4%) with MINS, 3633 (93.1%; 95% CI, 92.2%-93.8%) did not experience an ischemic symptom. Conclusions and Relevance Among patients undergoing noncardiac surgery, peak postoperative hsTnT during the first 3 days after surgery was significantly associated with 30-day mortality. Elevated postoperative hsTnT without an ischemic feature was also associated with 30-day mortality.

A simple benchmark for evaluating quality of care of patients following acute myocardial infarction

OBJECTIVE To develop a simple risk model as a basis for evaluating care of patients admitted with acute myocardial infarction. METHODS From coronary care registers, biochemistry records and hospital management systems, 2153 consecutive patients with confirmed acute myocardial infarction were identified. With 30 day all cause mortality as the end point, a multivariable logistic regression model of risk was constructed and validated in independent patient cohorts. The areas under receiver operating characteristic curves were calculated as an assessment of sensitivity and specificity. The model was reapplied to a number of commonly studied subgroups for further assessment of robustness. RESULTS A three variable model was developed based on age, heart rate, and systolic blood pressure on admission. This produced an individual probability of death by 30 days (P30) where P30 = 1/(1 + exp(−L30)) and L30 = −5.624 + (0.085 × age) + (0.014 × heart rate) − (0.022 × systolic blood pressure). The areas under the receiver operating characteristic curves for the reference and test cohorts were 0.79 (95% CI 0.76 to 0.82) and 0.76 (95% CI 0.72 to 0.79), respectively. To aid application of the model to routine clinical audit, a normogram relating observed mortality and sample size to the likelihood of a significant deviation from the expected 30 day mortality rate was constructed. CONCLUSIONS This risk model is simple, reproducible, and permits quality of care of acute myocardial infarction patients to be reliably evaluated both within and between centres.

Changing Characteristics and Mode of Death Associated With Chronic Heart Failure Caused by Left Ventricular Systolic DysfunctionClinical Perspective

Background—Therapies for patients with chronic heart failure caused by left ventricular systolic dysfunction have advanced substantially over recent decades. The cumulative effect of these therapies on mortality, mode of death, symptoms, and clinical characteristics has yet to be defined. Methods and Results—This study was a comparison of 2 prospective cohort studies of outpatients with chronic heart failure caused by left ventricular systolic dysfunction performed between 1993 and 1995 (historic cohort: n=281) and 2006 and 2009 (contemporary cohort: n=357). In the historic cohort, 83% were prescribed angiotensin-converting enzyme inhibitors and 8.5% were prescribed &bgr;-adrenoceptor antagonists, compared with 89% and 80%, respectively, in the contemporary cohort. Mortality rates over the first year of follow-up declined from 12.5% to 7.8% between eras (P=0.04), and sudden death contributed less to contemporary mortality (33.6% versus 12.7%; P<0.001). New York Heart Association class declined between eras (P<0.001). QTc dispersion across the chest leads declined from 85 ms (SD, 2) to 34 ms (SD, 1) and left ventricular end-diastolic dimensions declined from 65 mm (SD, 0.6) to 59 mm (SD, 0.5) (both P<0.001). Conclusions—Survival has significantly improved in patients with chronic heart failure caused by left ventricular systolic dysfunction over the past 15 years; furthermore, sudden death makes a much smaller contribution to mortality, and noncardiac mortality is a correspondingly greater contribution. This has been accompanied by an improvement in symptoms and some markers of adverse electric and structural left ventricular remodeling.

Under‐recognized complications in patients with paroxysmal nocturnal haemoglobinuria: raised pulmonary pressure and reduced right ventricular function

Pulmonary hypertension is becoming a recognized complication of the hereditary and acquired haemolytic anaemias, associated with a poor prognosis. Recently we reported that patients with paroxysmal nocturnal haemoglobinuria (PNH) have high levels of N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), a biomarker associated with both right and left ventricular dysfunction and cardiac dysfunction. In the current study we evaluated a cohort of patients (N = 29) with haemolytic PNH for elevated pulmonary artery systolic pressure and cardiac function by Doppler‐echocardiography. Of the 29 patients, eight were further studied using cardiac magnetic resonance imaging (MRI), as well as two additional patients (number of patients studied using cardiac MRI = 10). Plasma from the first cohort (N = 29) demonstrated intravascular haemolysis associated with a 12‐fold increase in median nitric oxide (NO) consumption when compared with healthy volunteers (P < 0·001). Doppler echocardiography demonstrated normal left ventricular function and elevated pulmonary artery systolic pressure in 41% of patients. Cardiac MRI from the second cohort (N = 10) demonstrated depressed right ventricular function in 80% of PNH patients tested, and 60% had findings suggestive of subclinical small pulmonary emboli. Together, these data suggest a high prevalence of haemolysis‐associated NO scavenging, Doppler‐estimated systolic pulmonary hypertension, and depressed right ventricular function in patients with PNH.

Review article: Diabetes mellitus and heart failure — an overview of epidemiology and management

Heart failure and Diabetes mellitus are chronic complex medical conditions that are closely related and commonly coexist.Treatment options have varied over the years, but newer treatment modalities have developed which have improved prognosis and longevity of patients with these conditions. Unfortunately, despite these advances, the evidence base remains insufficient, and larger randomised control trials need to be conducted. Here we discuss the available evidence and treatment and management of these inter-related conditions.

Prospective development and validation of a model to predict heart failure hospitalisation

Objective Acute heart failure syndrome (AHFS) is a major cause of hospitalisation and imparts a substantial burden on patients and healthcare systems. Tools to define risk of AHFS hospitalisation are lacking. Methods A prospective cohort study (n=628) of patients with stable chronic heart failure (CHF) secondary to left ventricular systolic dysfunction was used to derive an AHFS prediction model which was then assessed in a prospectively recruited validation cohort (n=462). Results Within the derivation cohort, 44 (7%) patients were hospitalised as a result of AHFS during 1 year of follow-up. Predictors of AHFS hospitalisation included furosemide equivalent dose, the presence of type 2 diabetes mellitus, AHFS hospitalisation within the previous year and pulmonary congestion on chest radiograph, all assessed at baseline. A multivariable model containing these four variables exhibited good calibration (Hosmer–Lemeshow p=0.38) and discrimination (C-statistic 0.77; 95% CI 0.71 to 0.84). Using a 2.5% risk cut-off for predicted AHFS, the model defined 38.5% of patients as low risk, with negative predictive value of 99.1%; this low risk cohort exhibited <1% excess all-cause mortality per annum when compared with contemporaneous actuarial data. Within the validation cohort, an identically applied model derived comparable performance parameters (C-statistic 0.81 (95% CI 0.74 to 0.87), Hosmer–Lemeshow p=0.15, negative predictive value 100%). Conclusions A prospectively derived and validated model using simply obtained clinical data can identify patients with CHF at low risk of hospitalisation due to AHFS in the year following assessment. This may guide the design of future strategies allocating resources to the management of CHF.

Association of Frontal QRS-T Angle–Age Risk Score on Admission Electrocardiogram With Mortality in Patients Admitted With an Acute Coronary Syndrome†

Risk assessment is central to the management of acute coronary syndromes. Often, however, assessment is not complete until the troponin concentration is available. Using 2 multicenter prospective observational studies (Evaluation of Methods and Management of Acute Coronary Events [EMMACE] 2, test cohort, 1,843 patients; and EMMACE-1, validation cohort, 550 patients) of unselected patients with acute coronary syndromes, a point-of-admission risk stratification tool using frontal QRS-T angle derived from automated measurements and age for the prediction of 30-day and 2-year mortality was evaluated. Two-year mortality was lowest in patients with frontal QRS-T angles <38° and highest in patients with frontal QRS-T angles >104° (44.7% vs 14.8%, p <0.001). Increasing frontal QRS-T angle-age risk (FAAR) scores were associated with increasing 30-day and 2-year mortality (for 2-year mortality, score 0 = 3.7%, score 4 = 57%; p <0.001). The FAAR score was a good discriminator of mortality (C statistics 0.74 [95% confidence interval 0.71 to 0.78] at 30 days and 0.77 [95% confidence interval 0.75 to 0.79] at 2 years), maintained its performance in the EMMACE-1 cohort at 30 days (C statistics 0.76 (95% confidence interval 0.71 to 0.8] at 30 days and 0.79 (95% confidence interval 0.75 to 0.83] at 2 years), in men and women, in ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction, and compared favorably with the Global Registry of Acute Coronary Events (GRACE) score. The integrated discrimination improvement (age to FAAR score at 30 days and at 2 years in EMMACE-1 and EMMACE-2) was p <0.001. In conclusion, the FAAR score is a point-of-admission risk tool that predicts 30-day and 2-year mortality from 2 variables across a spectrum of patients with acute coronary syndromes. It does not require the results of biomarker assays or rely on the subjective interpretation of electrocardiograms.