Pål H. Brekke

Statin use is associated with reduced mortality in COPD

Patients with chronic obstructive pulmonary disease (COPD) have an increased risk of ischaemic heart disease (IHD). Statins reduce mortality and morbidity in IHD. It has been hypothesised that statin treatment is associated with reduced long-term mortality in patients with COPD. Using a retrospective cohort design, 854 consecutive patients (mean age 70.8 yrs; 51.5% female) with a diagnosis of COPD exacerbation were included in the study at discharge from a Norwegian teaching hospital. Median follow-up was 1.9 yrs, during which 333 patients died. The crude mortality rate per 1,000 person-yrs was 110 in patients treated with statins, and 191 in patients not treated with statins. After adjustment for sex, age, smoking, pulmonary function and comorbidities, the hazard ratio (HR) for statin users versus statin nonusers was 0.57 (95% confidence interval 0.38–0.87). When subdividing statin users and statin nonusers into groups according to concomitant treatment with inhaled corticosteroids (ICS) the following HRs were found: 0.75 (0.58–0.98) for ICS only; 0.69 (0.36–1.3) for statins only; and 0.39 (0.22–0.67) for the combined treatment with statin and ICS compared with no such treatment. Treatment with statins was associated with improved survival after chronic obstructive pulmonary disease exacerbation, while inhaled corticosteroids appeared to increase the survival benefit associated with statin use.

Elevated high-sensitivity cardiac troponin T is associated with increased mortality after acute exacerbation of chronic obstructive pulmonary disease

Background Cardiovascular co-morbidities are common in chronic obstructive pulmonary disease (COPD). Retrospective studies on selected patients have indicated that cardiac troponin elevation is frequent during acute exacerbations of COPD (AECOPD), and that this is associated with poor survival. In the present prospective study the prevalence and prognostic value of elevated cardiac troponin T (cTnT) in unselected patients with AECOPD have been investigated, using a novel high-sensitivity assay (hs-cTnT assay). Methods and results 99 patients hospitalised for AECOPD were included. They were followed until death or study termination. During a median follow-up time of 1.9 years, 57 patients (58%) died. 97 patients (98%) had measurable levels of hs-cTnT and 73 (74%) had hs-cTnT above the normal range (≥14.0 ng/l). The crude mortality rates in patients having hs-cTnT <14.0, 14.0–39.9 and ≥40 ng/l were 4.6, 30.2 and 58.3 per 100 patient-years, respectively. Adjusting for relevant covariables using an extended Cox regression analysis, the HRs (95% CI) for death were 4.5 (1.2 to 16) and 8.9 (2.4 to 32) among patients having hs-cTnT 14.0–39.9 and ≥40 ng/l, respectively, compared with patients with hs-cTnT <14.0 ng/l. The association between mortality and hs-cTnT was strongly modified by heart rate at admission (p<0.001)—that is, the association between mortality and hs-cTnT was stronger among patients with tachycardia. Conclusion Elevated hs-cTnT during AECOPD is frequent, and it is associated with increased mortality. The effect is stronger among patients having tachycardia than among patients with normal heart rate.

Troponin T elevation and long-term mortality after chronic obstructive pulmonary disease exacerbation

Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of cardiovascular disease, exacerbations of which increase strain on the heart. The prognostic value of elevated circulating levels of cardiac Troponins seen during COPD exacerbations has been investigated. From the Akershus hospital database, 897 patients discharged after treatment for COPD exacerbation in the period 2000–2003 were identified and followed-up until June 30, 2005. Median observation time was 1.9 yrs. In 396 patients, measurements of cardiac-specific troponin T (cTnT) were available. Levels of cTnT ≥0.04 μg·L−1 were considered elevated. Clinical data were retrieved from patient records and date of death was obtained from the Norwegian National Registry. In order to balance the nonrandomised nature of available cTnT measurements, an exposure propensity score (EPS) for cTnT sampling was calculated and used in regression analyses. After adjusting for EPS in Cox regression analyses, elevated cTnT was significantly associated with increased all-cause mortality in the observation period, with a hazard ratio of 1.64 (95% confidence interval 1.15–2.34). In conclusion, chronic obstructive pulmonary disease patients with elevated cardiac-specific Troponin T during exacerbation are at increased risk of death after discharge.

NT-proBNP independently predicts long term mortality after acute exacerbation of COPD - a prospective cohort study

BackgroundCardiovascular disease is prevalent and frequently unrecognized in patients with chronic obstructive pulmonary disease (COPD). NT-proBNP is an established risk factor in patients with heart failure. NT-proBNP may also be released from the right ventricle. Thus serum NT-proBNP may be elevated during acute exacerbations of COPD (AECOPD). The prognostic value of NT-proBNP in patients hospitalized with AECOPD is sparsely studied. Our objective was to test the hypothesis that NT-proBNP independently predicts long term mortality following AECOPD.MethodsA prospective cohort study of 99 patients with 217 admissions with AECOPD. Clinical, electrocardiographic, radiological and biochemical data were collected at index and repeat admissions and analyzed in an extended survival analysis with time-dependent covariables.ResultsMedian follow-up time was 1.9 years, and 57 patients died during follow-up. NT-proBNP tertile limits were 264.4 and 909 pg/mL, and NT-proBNP in tertiles 1 through 3 was associated with mortality rates of 8.6, 35 and 62 per 100 patient-years, respectively (age-adjusted log-rank p<0.0001). After adjustment for age, gender, peripheral edema, cephalization and cTnT in a multivariable survival model, the corresponding hazard ratios for dying were 2.4 (0.95-6.0) and 3.2 (1.3-8.1) (with 95% confidence intervals in parentheses, p-value for trend 0.013).ConclusionsNT-proBNP is a strong and independent determinant of mortality after AECOPD.

Determinants of cardiac troponin T elevation in COPD exacerbation – a cross-sectional study

BackgroundCardiac Troponin T (cTnT) elevation during exacerbations of chronic obstructive pulmonary disease (COPD) is associated with increased mortality the first year after hospital discharge. The factors associated with cTnT elevation in COPD are not known.MethodsFrom our hospitals database, all patients admitted with COPD exacerbation in 2000–03 were identified. 441 had measurement of cTnT performed. Levels of cTnT ≥ 0.04 μg/l were considered elevated. Clinical and historical data were retrieved from patient records, hospital and laboratory databases. Odds ratios for cTnT elevation were calculated using logistic regression.Results120 patients (27%) had elevated cTnT levels. The covariates independently associated with elevated cTnT were increasing neutrophil count, creatinine concentration, heart rate and Cardiac Infarction Injury Score (CIIS), and decreasing hemoglobin concentration. The adjusted odds ratios (95% confidence intervals in parentheses) for cTnT elevation were 1.52 (1.20–1.94) for a 5 × 106/ml increase in neutrophils, 1.21 (1.12–1.32) for a 10 μmol/l increase in creatinine, 0.80 (0.69–0.92) for a 1 mg/dl increase in hemoglobin, 1.24 (1.09–1.42) for a 10 beats/minute increase in heart rate and 1.44 (1.15–1.82) for a 10 point increase in CIIS.ConclusionMultiple factors are associated with cTnT elevation, probably reflecting the wide panorama of comorbid conditions typically seen in COPD. The positive association between neutrophils and cTnT elevation is compatible with the concept that an exaggerated inflammatory response in COPD exacerbation may predispose for myocardial injury.

Determinants of high-sensitivity cardiac troponin T during acute exacerbation of chronic obstructive pulmonary disease: a prospective cohort study

BackgroundA high-sensitivity cardiac troponin T (hs-cTnT) concentration above the 99th percentile (i.e. 14 ng/L) is common during Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD) and associated with increased mortality. The objective of the study was to identify factors associated with hs-cTnT levels during AECOPD.MethodsWe included 99 patients with AECOPD on admission. As 41 patients had one or more repeat admissions, there were 202 observations in the final analysis. We recorded clinical and biochemical data, medication, spirometry, chest radiographs, and ECGs. The data were analysed for cross-sectional and longitudinal associations using ordinary least square as well as linear mixed models with the natural logarithm of hs-cTnT as the dependent variable.ResultsMean age at inclusion was 71.5 years, mean FEV1/FVC was 45%, and median hs-cTnT was 27.0 ng/L. In a multivariable model there was a 24% increase in hs-cTnT per 10 years increase in age (p < 0.0001), a 6% increase per 10 μmol/L increase in creatinine (p = 0.037), and a 2% increase per month after enrollment (p = 0.046). Similarly, the ratios of hs-cTnT between patients with and without tachycardia (heart rate ≥100/min) and with and without history of arterial hypertension were 1.25 (p = 0.042) and 1.44 (p = 0.034), respectively. We found no significant association between arterial hypoxemia and elevated hs-cTnT.ConclusionAge, arterial hypertension, tachycardia, and serum creatinine are independently associated with the level of hs-cTnT on admission for AECOPD.

Lamin A/C cardiomyopathy: young onset, high penetrance, and frequent need for heart transplantation

Abstract Aims Lamin A/C (LMNA) mutations cause familial dilated cardiomyopathy (DCM) with frequent conduction blocks and arrhythmias. We explored the prevalence, cardiac penetrance, and expressivity of LMNA mutations among familial DCM in Norway. Furthermore, we explored the risk factors and the outcomes in LMNA patients. Methods and results During 2003–15, genetic testing was performed in patients referred for familial DCM. LMNA genotype-positive subjects were examined by electrocardiography, Holter monitoring, cardiac magnetic resonance imaging, and echocardiography. A positive cardiac phenotype was defined as the presence of atrioventricular (AV) block, atrial fibrillation/flutter (AF), ventricular tachycardia (VT), and/or echocardiographic DCM. Heart transplantation was recorded and compared with non-ischaemic DCM of other origin. Of 561 unrelated familial DCM probands, 35 (6.2%) had an LMNA mutation. Family screening diagnosed an additional 93 LMNA genotype-positive family members. We clinically followed up 79 LMNA genotype-positive [age 42 ± 16 years, ejection fraction (EF) 45 ± 13%], including 44 (56%) with VT. Asymptomatic LMNA genotype-positive family members (age 31 ± 15 years) had a 9% annual incidence of a newly documented cardiac phenotype and 61% (19/31) of cardiac penetrance during 4.4 ± 2.9 years of follow-up. Ten (32%) had AV block, 7 (23%) AF, and 12 (39%) non-sustained VT. Heart transplantation was performed in 15 of 79 (19%) LMNA patients during 7.8 ± 6.3 years of follow-up. Conclusion LMNA mutation prevalence was 6.2% of familial DCM in Norway. Cardiac penetrance was high in young asymptomatic LMNA genotype-positive family members with frequent AV block and VT, highlighting the importance of early family screening and cardiological follow-up. Nearly 20% of the LMNA patients required heart transplantation.

The clinical value of serial measurement of high-sensitivity cardiac troponin T in acute exacerbations ofchronic obstructive pulmonary disease

Objective To assess the prevalence and long-term prognostic value of a dynamic (rise/fall) pattern of cardiac troponin T (hs-cTnT) elevation during acute exacerbation of chronic obstructive pulmonary disease (AECOPD) compared with a stable hs-cTnT elevation. Methods Prospective cohort study of unselected patients admitted with AECOPD to the emergency room of a university hospital. Serial hs-cTnT measurements were made during admission. Survival after a median of 1.8 years was recorded. Results 83 patients with a mean age of 72 years and a mean forced expiratory volume in 1 s (FEV1) of 0.9 L. The mortality rate was 62%. The median hs-cTnT at admission was 27 ng/L (IQR 13.4–51)). 65 patients (78%) had at least one hs-cTnT measurement ≥14 ng/L, and among these the median change in hs-cTnT was 50.7% (IQR 25.2–89.4). Of the patients with serial hs-cTnT measurements, 53 (82%) had a dynamic pattern (ie, ΔTnT ≥20%). In multivariate analysis, stable hs-cTnT elevation was associated with increasing age (OR per 5 years with 95% CI 1.9 (1.01 to 3.7), p=0.045) and low Hb (OR 7.3 (1.1 to 49), p=0.039). Stable hs-cTnT elevation was associated with increased mortality with an HR of 2.4 (95%CI 1.1 to 5.3, p=0.027) in the multivariate Cox regression analysis. Conclusions Among the patients with at least one hs-cTnT above the 99th centile, 82% had a rise/fall pattern, as requested to make a diagnosis of myocardial infarction. Compared to a dynamic rise/fall pattern of hs-cTnT, a stable and moderately elevated hs-cTnT during AECOPD is associated with poor long-term prognosis.

Prognostic Value of Left Ventricular Deformation Parameters in Patients with Severe Aortic Stenosis: A Pilot Study of the Usefulness of Strain Echocardiography

Background: In patients with aortic stenosis, subtle alterations in myocardial mechanics can be detected by speckle‐tracking echocardiography before reduction of left ventricular ejection fraction (LVEF). Methods: In this prospective study, 162 patients with aortic stenosis with an average aortic valve area of 0.7 ± 0.2 cm2 and a mean LVEF of 60 ± 11% were included. Global longitudinal strain (GLS) and mechanical dispersion (SD of time from Q/R on the electrocardiogram to peak strain in 16 left ventricular segments) were assessed using echocardiography, and all‐cause mortality (n = 37) was recorded during 37 ± 13 months of follow‐up. Results: Overall, nonsurvivors had more pronounced mechanical dispersion and worse GLS compared with survivors (74 ± 24 vs 61 ± 18 msec [P < .01] and −14.5 ± 4.4% vs −16.7 ± 3.6% [P < .01], respectively). In the 42 conservatively treated patients without surgical aortic valve replacement, a similar pattern was observed in nonsurvivors versus survivors (mechanical dispersion, 80 ± 24 vs 57 ± 14 msec [P < .01]; GLS, −14.0 ± 4.9% vs −17.1 ± 3.8% [P = .04], respectively). Mechanical dispersion was significantly associated with mortality (hazard ratio per 10‐msec increase, 1.23; 95% CI, 1.07–1.42; P < .01) in a Cox model adjusted for LVEF and with aortic valve replacement treatment as a time‐dependent covariate. Continuous net reclassification improvement showed that mechanical dispersion was incremental to LVEF, GLS, and valvulo‐arterial impedance when adjusting for aortic valve replacement treatment in the total population. Conclusion: Increased mechanical dispersion may be a risk marker providing novel prognostic information in patients with aortic stenosis. Graphical abstract Figure. No caption available. HighlightsStrain echocardiography can detect altered myocardial mechanics in patients with AS.Pronounced mechanical dispersion is associated with worse prognosis in patients with AS.Mechanical dispersion adds incremental prognostic value to LVEF, atrioventricular impedance, and global longitudinal strain.Mechanical dispersion predicts mortality independently of LVEF and AVR surgery status.

Standardized evaluation of lung congestion during COPD exacerbation better identifies patients at risk of dying.

Background Congestive heart failure is underdiagnosed in patients with chronic obstructive pulmonary disease (COPD). Pulmonary congestion on chest radiograph at admission for acute exacerbation of COPD (AECOPD) is associated with an increased risk of mortality. A standardized evaluation of chest radiographs may enhance prognostic accuracy. Purpose We aimed to evaluate whether a standardized, liberal assessment of pulmonary congestion is superior to the routine assessment in identifying patients at increased risk of long-term mortality, and to investigate the association of heart failure with N-terminal prohormone of brain natriuretic peptide (NT-proBNP) concentrations. Material and methods This was a prospective cohort study of 99 patients admitted for AECOPD. Chest radiographs obtained on admission were routinely evaluated and then later evaluated by blinded investigators using a standardized protocol looking for Kerley B lines, enlarged vessels in the lung apex, perihilar cuffing, peribronchial haze, and interstitial or alveolar edema, defining the presence of pulmonary congestion. Adjusted associations with long-term mortality and NT-proBNP concentration were calculated. Results The standardized assessment was positive for pulmonary congestion in 32 of the 195 radiographs (16%) ruled negative in the routine assessment. The standardized assessment was superior in predicting death during a median follow up of 1.9 years (P=0.022), and in multivariable analysis, only the standardized assessment showed a significant association with mortality (hazard ratio 2.4, 95% confidence interval [CI] 1.2–4.7) (P=0.016) and NT-proBNP (relative concentration 1.8, CI 1.2–2.6) (P=0.003). Conclusion By applying a standardized approach when evaluating pulmonary congestion on chest radiographs during AECOPD, a group of patients with increased risk of dying, possibly due to heart failure, is identified.