Frants Pedersen

The influence of age, sex and other variables on the plasma level of N-terminal pro brain natriuretic peptide in a large sample of the general population

Objective: To identify potentially confounding variables for the interpretation of plasma N-terminal pro brain natriuretic peptide (NT-proBNP). Design: Randomly selected subjects filled in a heart failure questionnaire and underwent pulse and blood pressure measurements, ECG, echocardiography, and blood sampling. Setting: Subjects were recruited from four Copenhagen general practices located in the same urban area and were examined in a Copenhagen University Hospital. Patients: 382 women and 290 men in four age groups: 50–59 years (n = 174); 60–69 years (n = 204); 70–79 years (n = 174); and > 80 years (n = 120). Main outcome measures: Associations between the plasma concentration of NT-proBNP and a range of clinical variables. Results: In the undivided study sample, female sex (p < 0.0001), greater age (p < 0.0001), increasing dyspnoea (p = 0.0001), diabetes mellitus (p = 0.01), valvar heart disease (p = 0.002), low heart rate (p < 0.0001), left ventricular ejection fraction ⩽ 45% (p < 0.0001), abnormal ECG (p < 0.0001), high log10[plasma creatinine] (p = 0.0009), low log10[plasma glycosylated haemoglobin A1c] (p = 0.0004), and high log10[urine albumin] (p < 0.0001) were independently associated with a high plasma log10[plasma NT-proBNP] by multiple linear regression analysis. Conclusions: A single reference interval for the normal value of NT-proBNP is unlikely to suffice. There are several confounders for the interpretation of a given NT-proBNP concentration and at the very least adjustment should be made for the independent effects of age and sex.

Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events

AIMS Patients with chest pain and no obstructive coronary artery disease (CAD) are considered at low risk for cardiovascular events but evidence supporting this is scarce. We investigated the prognostic implications of stable angina pectoris in relation to the presence and degree of CAD with no obstructive CAD in focus. METHODS AND RESULTS We identified 11 223 patients referred for coronary angiography (CAG) in 1998-2009 with stable angina pectoris as indication and 5705 participants from the Copenhagen City Heart Study for comparison. Main outcome measures were major adverse cardiovascular events (MACE), defined as cardiovascular death, myocardial infarction, stroke or heart failure, and all-cause mortality. Significantly more women (65%) than men (32%) had no obstructive CAD (P< 0.001). In Coxs models adjusted for age, body mass index, diabetes, smoking, and use of lipid-lowering or antihypertensive medication, hazard ratios (HRs) associated with no obstructive CAD were similar in men and women. In the pooled analysis, the risk of MACE increased with increasing degrees of CAD with multivariable-adjusted HRs of 1.52 (95% confidence interval, 1.27-1.83) for patients with normal coronary arteries and 1.85 (1.51-2.28) for patients with diffuse non-obstructive CAD compared with the reference population. For all-cause mortality, normal coronary arteries and diffuse non-obstructive CAD were associated with HRs of 1.29 (1.07-1.56) and 1.52 (1.24-1.88), respectively. CONCLUSION Patients with stable angina and normal coronary arteries or diffuse non-obstructive CAD have elevated risks of MACE and all-cause mortality compared with a reference population without ischaemic heart disease.

Complete revascularisation versus treatment of the culprit lesion only in patients with ST-segment elevation myocardial infarction and multivessel disease (DANAMI-3—PRIMULTI): an open-label, randomised controlled trial.

BACKGROUND Patients with acute ST-segment elevation myocardial infarction (STEMI) and multivessel coronary disease have a worse prognosis compared with individuals with single-vessel disease. We aimed to study the clinical outcome of patients with STEMI treated with fractional flow reserve (FFR)-guided complete revascularisation versus treatment of the infarct-related artery only. METHODS We undertook an open-label, randomised controlled trial at two university hospitals in Denmark. Patients presenting with STEMI who had one or more clinically significant coronary stenosis in addition to the lesion in the infarct-related artery were included. After successful percutaneous coronary intervention (PCI) of the infarct-related artery, patients were randomly allocated (in a 1:1 ratio) either no further invasive treatment or complete FFR-guided revascularisation before discharge. Randomisation was done electronically via a web-based system in permuted blocks of varying size by the clinician who did the primary PCI. All patients received best medical treatment. The primary endpoint was a composite of all-cause mortality, non-fatal reinfarction, and ischaemia-driven revascularization of lesions in non-infarct-related arteries and was assessed when the last enrolled patient had been followed up for 1 year. Analysis was on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01960933. FINDINGS From March, 2011, to February, 2014, we enrolled 627 patients to the trial; 313 were allocated no further invasive treatment after primary PCI of the infarct-related artery only and 314 were assigned complete revascularization guided by FFR values. Median follow-up was 27 months (range 12–44 months). Events comprising the primary endpoint were recorded in 68 (22%) patients who had PCI of the infarct-related artery only and in 40 (13%) patients who had complete revascularisation (hazard ratio 0∙56, 95% CI 0∙38–0∙83; p=0∙004). INTERPRETATION In patients with STEMI and multivessel disease, complete revascularisation guided by FFR measurements significantly reduces the risk of future events compared with no further invasive intervention after primary PCI. This effect is driven by significantly fewer repeat revascularisations, because all-cause mortality and non-fatal reinfarction did not differ between groups. Thus, to avoid repeat revascularisation, patients can safely have all their lesions treated during the index admission. Future studies should clarify whether complete revascularization should be done acutely during the index procedure or at later time and whether it has an effect on hard endpoints. FUNDING Danish Agency for Science, Technology and Innovation and Danish Council for Strategic Research.

Diagnostic and prognostic evaluation of left ventricular systolic heart failure by plasma N-terminal pro-brain natriuretic peptide concentrations in a large sample of the general population

Objective: To evaluate N-terminal pro-brain natriuretic peptide (NT-proBNP) as a diagnostic and prognostic marker for systolic heart failure in the general population. Design: Study participants, randomly selected to be representative of the background population, filled in a heart failure questionnaire and underwent pulse and blood pressure measurements, electrocardiography, echocardiography, and blood sampling and were followed up for a median (range) period of 805 (60−1171) days. Setting: Participants were recruited from four randomly selected general practitioners and were examined in a Copenhagen university hospital. Patients: 382 women and 290 men in four age groups (50−59 (n  =  174); 60−69 (n  =  204); 70−79 (n  =  174); ⩾ 80 years (n  =  120)). Main outcome measures: Value of NT-proBNP in evaluating patients with symptoms of heart failure and impaired left ventricular (LV) systolic function; prognostic value of NT-proBNP for mortality and hospital admissions. Results: In 38 (5.6%) participants LV ejection fraction (LVEF) was ⩽ 40%. NT-proBNP identified patients with symptoms of heart failure and LVEF ⩽ 40% with a sensitivity of 0.92, a specificity of 0.86, positive and negative predictive values of 0.11 and 1.00, and area under the curve of 0.94. NT-proBNP was the strongest independent predictor of mortality (hazard ratio (HR)  =  5.70, p < 0.0001), hospital admissions for heart failure (HR  =  13.83, p < 0.0001), and other cardiac admissions (HR  =  3.69, p < 0.0001). Mortality (26 v 6, p  =  0.0003), heart failure admissions (18 v 2, p  =  0.0002), and admissions for other cardiac causes (44 v 13, p < 0.0001) were significantly higher in patients with NT-proBNP above the study median (32.5 pmol/l). Conclusions: Measurement of NT-proBNP may be useful as a screening tool for systolic heart failure in the general population.

N-terminal-pro-B-type natriuretic peptide (NT-pro-BNP) in different thyroid function states.

objective  N‐terminal B‐type natriuretic peptide (NT‐pro‐BNP) is secreted from the cardiac ventricles in response to volume expansion and pressure overload, and serum levels are elevated in systolic heart failure. The aim of this study was to evaluate the influence of thyroid function on NT‐pro‐BNP.

Emergency coronary angiography in comatose cardiac arrest patients: do real-life experiences support the guidelines?

Aims: To describe the use of emergency coronary angiography (CAG) and primary percutaneous coronary intervention (PCI) and the association with short- and long-term survival in consecutive comatose survivors after out-of-hospital cardiac arrest (OHCA). Methods: In the period 2004–10, a total of 479 consecutive patients with OHCA of suspected cardiac cause were referred to a tertiary cardiac centre, 360 patients were comatose and admitted to the ICU for post-resuscitative care. The population was stratified in two groups according to the pattern of the first ECG obtained after re-established circulation; ST-segment elevation (STEMI, n=116) and ECG without STEMI pattern (No-STEMI, n=244). Emergency CAG (≤12 hours after OHCA) was performed at the discretion of the attending cardiologist. Primary outcome was 30-day and 1-year survival. Results: Emergency CAG was performed in all patients in the STEMI group compared to 82 (34%) in the group without STEMI pattern (p<0.0001) with significant coronary lesions found in 108 (93%) compared to 43 (52%) patients, respectively (p<0.0001). Survival at 30 day according to emergency CAG vs. no emergency CAG was 65% in the STEMI group compared to 66% and 54% in the group without STEMI pattern (plog-rank=0.11). The use of emergency CAG in the group without STEMI pattern was not associated with reduced mortality (HRadjusted=0.69, 95% CI 0.4–1.2, p=0.18). Conclusions: In comatose survivors of OHCA presenting with STEMI, a high prevalence of coronary disease and culprit lesions suitable for emergency PCI was found, whereas in patients without STEMI pattern, significant coronary stenosis was less frequent. Clinical benefits of emergency CAG/PCI in comatose survivors of OHCA presenting without STEMI could not be identified.

Tertiary centres have improved survival compared to other hospitals in the Copenhagen area after out-of-hospital cardiac arrest ☆

AIMS Out-of-hospital cardiac arrest (OHCA) has been reported to carry very varying morbidity and mortality. However, it remains unclear whether this is caused by intrinsic factors of the OHCA or due to the level of in-hospital care. The aim of this study is to compare 30-day and long-term mortality after OHCA at tertiary heart centres and non-tertiary university hospitals. METHODS AND RESULTS Data from the Copenhagen OHCA registry from June 2002 through December 2010 included a total of 1218 consecutive patients treated by the same mobile emergency care unit (MECU) with either return of spontaneous circulation (ROSC) or on-going resuscitation (n=53) at hospital arrival. The MECU transported patients to the nearest hospital unless an ECG on scene suggested ST-segment elevation myocardial infarction, in which case patients were transported to the nearest tertiary centre for acute coronary angiography. Therefore, patients with ST-elevation myocardial infarction (n=198) were excluded from the analysis. 30-day mortality was 56% vs. 76% and long term (up to 8years) mortality was 78% vs. 94% for tertiary and non-tertiary hospitals, respectively, both p<0.001. Multivariate analysis showed that admission to a non-tertiary hospital was independently associated with increased risk of death (HR=1.32, 95% CI: 1.09-1.59, p=0.004). Exclusion of patients with on-going resuscitation at admission resulted in HR=1.34 (1.11-1.62), p=0.003. A matched pair propensity score analysis of 255 patients confirmed the results of the proportional hazard analysis (HR=1.35, 95% CI: 1.11-1.65 p=0.003). CONCLUSION Admission to tertiary centres is associated with lower mortality rates after OHCA compared with non-tertiary hospitals.

Prevalence of impaired left ventricular systolic function and heart failure in a middle aged and elderly urban population segment of Copenhagen

Objective: To assess the prevalence of impaired left ventricular systolic function and manifest heart failure in a general population aged 50–89 years. Design: In this cross sectional survey, participants filled in a heart failure questionnaire. ECG, blood tests, and echocardiography were performed. Setting: The study population was recruited from general practitioners situated in the same urban area and examined in a university hospital in Copenhagen, Denmark. Participants: 764 participants (432 women and 332 men, median (SD) age 66 (11) years) participated. The study population was stratified to include a minimum of 150 persons in each age decade. Main outcome measures: Prevalence of impaired systolic function and manifest heart failure. Results: The prevalence of systolic dysfunction (left ventricular ejection fraction ⩽ 40%) was more than twice as high among men (7.6%) as among women (2.6%). In the male population systolic heart failure (left ventricular ejection fraction ⩽ 40% and symptoms) was found in 1.8% of the 50–59 years age group and approximately doubled for each age decade to reach 13.9% in octogenarians. Among women systolic dysfunction increased from 0.8% to 4.3% in the same age groups. Asymptomatic cases accounted for 44.0% of all cases of systolic dysfunction in the male population and only 9.1% in the female population. Conclusions: In this age controlled population study impaired left ventricular systolic function and heart failure increased substantially with age and was more than twice as frequent among men as among women. Asymptomatic left ventricular dysfunction occurred more frequently in men than in women and was less prevalent with increasing age.

Deferred stent implantation in patients with ST-segment elevation myocardial infarction: a pilot study

AIMS Disturbance in the flow of an infarct-related artery due to embolisation of thrombus and plaque material occurs frequently during primary percutaneous coronary intervention (PCI) and is associated with impaired prognosis. The aim of the present study was to minimise the risk of embolisation during PCI in patients with ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS Of 124 consecutive patients with STEMI, thrombectomy and/or balloon dilatation was performed in 110 (89%). Stent implantation was deferred in 113 (91%) patients who then comprised the study group. In 38% of the patients stent implantation was deemed unnecessary at the second examination because of <30% residual stenosis and no visible thrombus, and all lesions re-examined three months later were patent. Major adverse cardiac events occurred in two patients during eight months of follow-up (one cardiac death, one case of reinfarction with target lesion revascularisation). In five patients no PCI was performed at all. Myocardial salvage determined by cardiac magnetic resonance in a subset of patients was relatively high. CONCLUSIONS Deferred stent implantation is safe in the majority of patients with STEMI. Although the concept has to be evaluated in a randomised trial, the strategy may prove beneficial for many patients referred for primary PCI.

Incidence and Risk Factors of Ventricular Fibrillation Before Primary Angioplasty in Patients With First ST-Elevation Myocardial Infarction: A Nationwide Study in Denmark

Background We aimed to investigate the incidence and risk factors for ventricular fibrillation (VF) before primary percutaneous coronary intervention (PPCI) among patients with ST‐segment elevation myocardial infarction (STEMI) in a prospective nationwide setting. Methods and Results In this case‐control study, patients presenting within the first 12 hours of first STEMI who survived to undergo angiography and subsequent PPCI were enrolled. Over 2 years, 219 cases presenting with VF before PPCI and 441 controls without preceding VF were enrolled. Of the 219 case patients, 182 (83%) had STEMI with out‐of‐hospital cardiac arrest due to VF, and 37 (17%) had cardiac arrest upon arrival to the emergency room. Medical history was collected by standardized interviews and by linkage to national electronic health records. The incidence of VF before PPCI among STEMI patients was 11.6%. Multivariable logistic regression analysis identified novel associations between atrial fibrillation and alcohol consumption with VF. Patients with a history of atrial fibrillation had a 2.80‐fold odds of experiencing VF before PPCI (95% CI 1.10 to 7.30). Compared with nondrinkers, patients who consumed 1 to 7 units, 8 to 14 units, or >15 units of alcohol per week had an odds ratio (OR) of 1.30 (95% CI, 0.80 to 2.20), 2.30 (95% CI, 1.20 to 4.20), or 3.30 (95% CI, 1.80 to 5.90), respectively, for VF. Previously reported associations for preinfarction angina (OR 0.46; 95% CI 0.32 to 0.67), age of <60 years (OR 1.75; 95% CI 1.20 to 2.60), anterior infarction (OR 2.10; 95% CI 1.40 to 3.00), preprocedural thrombolysis in myocardial infarction flow grade 0 (OR 1.65; 95% CI 1.14 to 2.40), and family history of sudden death (OR 1.60; 95% CI 1.10 to 2.40) were all associated with VF. Conclusion Several easily assessed risk factors were associated with VF occurring out‐of‐hospital or on arrival at the emergency room before PPCI in STEMI patients, thus providing potential avenues for investigation regarding improved identification and prevention of life‐threatening ventricular arrhythmias.