Objectives This study sought to determine the prognostic value of B-type natriuretic peptide (BNP) in patients with heart failure with preserved ejection fraction (HFPEF), in comparison to data in HF ...patients with reduced left ventricular (LV) EF (≤40%). Background Management of patients with HFPEF is difficult. BNP is a useful biomarker in patients with reduced LVEF, but data in HFPEF are scarce. Methods In this study, 615 patients with mild to moderate HF (mean age 70 years, LVEF 33%) were followed for 18 months. BNP concentrations were measured at baseline and were related to the primary outcome, that is, a composite of all-cause mortality and HF hospitalization, and to mortality alone. The population was divided in quintiles, according to LVEF, and patients with reduced LVEF were compared with those with HFPEF. Results There were 257 patients (42%) who had a primary endpoint and 171 (28%) who died. BNP levels were significantly higher in patients with reduced LVEF than in those with HFPEF (p < 0.001). BNP was a strong predictor of outcome, but LVEF was not. Importantly, if similar levels of BNP were compared across the whole spectrum of LVEF, and for different cutoff levels of LVEF, the associated risk of adverse outcome was similar in HFPEF patients as in those with reduced LVEF. Conclusions BNP levels are lower in patients with HFPEF than in patients with HF with reduced LVEF, but for a given BNP level, the prognosis in patients with HFPEF is as poor as in those with reduced LVEF.
Abstract Purpose Diagnostic prediction models such as the Wells rule can be used for safely ruling out pulmonary embolism (PE) when it is suspected. A physician's own probability estimate ...(“gestalt”), however, is commonly used instead. We evaluated the diagnostic performance of both approaches in primary care. Methods Family physicians estimated the probability of PE on a scale of 0% to 100% (gestalt) and calculated the Wells rule score in 598 patients with suspected PE who were thereafter referred to secondary care for definitive testing. We compared the discriminative ability (c statistic) of both approaches. Next, we stratified patients into PE risk categories. For gestalt, a probability of less than 20% plus a negative point-of-care D-dimer test indicated low risk; for the Wells rule, we used a score of 4 or lower plus a negative D-dimer test. We compared sensitivity, specificity, efficiency (percentage of low-risk patients in total cohort), and failure rate (percentage of patients having PE within the low-risk category). Results With 3 months of follow-up, 73 patients (12%) were confirmed to have venous thromboembolism (a surrogate for PE at baseline). The c statistic was 0.77 (95% CI, 0.70–0.83) for gestalt and 0.80 (95% CI, 0.75–0.86) for the Wells rule. Gestalt missed 2 out of 152 low-risk patients (failure rate = 1.3%; 95% CI, 0.2%–4.7%) with an efficiency of 25% (95% CI, 22%–29%); the Wells rule missed 4 out of 272 low-risk patients (failure rate = 1.5%; 95% CI, 0.4%–3.7%) with an efficiency of 45% (95% CI, 41%–50%). Conclusions Combined with D-dimer testing, both gestalt using a cutoff of less than 20% and the Wells rule using a score of 4 or lower are safe for ruling out PE in primary care. The Wells rule is more efficient, however, and PE can be ruled out in a larger proportion of suspected cases.
Highlights • Using individual patient data of 20 trials (5624 patients), different components of self-management in heart failure were compared • Specific characteristics of self-management programs ...may be more effective than others • A longer duration of interventions improved several health-related outcomes • This study showed that more attention is needed for understanding the working mechanism of interventions
Abstract Purpose The Wells rule is widely used for clinical assessment of patients with suspected deep vein thrombosis (DVT), especially in the secondary care setting. Recently a new clinical ...decision rule for primary care patients (the primary care rule) has been proposed, because the Wells rule is not sufficient to rule out DVT in this setting. The objective was to compare the ability of both rules to safely rule out DVT and to efficiently reduce the number of referrals for leg ultrasound investigation that would result in a negative finding. Methods Family physicians collected data on 1,086 patients to calculate the scores for both decision rules before leg ultrasonography was performed. In all patients D-dimer (dimerized plasmin fragment D) testing was performed using a rapid point-of-care assay. Patients were stratified into risk categories defined by each rule and the D-dimer result. Outcomes were DVT (diagnosed by ultrasonography) and venous thromboembolic complications or death caused by a possible thromboembolic event during a 90-day follow-up period. We calculated the differences between the 2 rules in the number of missed diagnoses and the proportions of patients that needed ultrasound testing. Results Data from 1,002 eligible patients were used for this analysis. A venous thromboembolic event occurred during follow-up in 7 patients with a low score and negative D-dimer finding, both with the Wells rule (7 of 447; 1.6%; 95% confidence interval CI, 0.7%-3.3%) and the primary care rule (7 of 495; 1.4%; 95% CI, 0.6%-3.0%). Using the Wells rule, 447 patients (45%) would not need referral for further testing compared with 495 patients (49%) when using the primary care rule (McNemar P <.001). Conclusions In primary care, suspected DVT can safely be ruled out using either of the 2 rules in combination with a point-of-care D-dimer test. Both rules can reduce unnecessary referrals for compression ultrasonography by about 50%, though the primary care rule reduces it slightly more.
Abstract Background Pulmonary restriction—a reduction of lung volumes—is common in heart failure (HF), rendering severity grading of chronic obstructive pulmonary disease (COPD) potentially ...problematic in subjects with both diseases. We compared pulmonary function in patients with either HF or COPD, or the combination to assess whether grading of COPD using the Global Initiative of Chronic Obstructive Lung Disease classification is hampered in the presence of HF. Methods and Results In 2 cohorts involving 591 patients with established HF and 405 with a primary care diagnosis of COPD, the presence of HF and COPD was assessed according to guidelines. HF severity was staged according to the NYHA classification system into Classes I–IV. COPD was diagnosed if the ratio of post-bronchodilator forced expiratory volume in 1 second and forced vital capacity (FEV1/FVC) was <0.70, and categorized in GOLD stages I–IV according to post-bronchodilator–predicted FEV1 levels (FEV1% ≥80%; 50–79%; 30–49%; <30%). In total, 557 patients with HF only, 108 with HF+COPD, and 194 with COPD only were studied. Patients, who had neither HF nor COPD according to definition, or HF with reversible obstruction in post-bronchodilator pulmonary function tests were excluded from this analysis (n = 137). Compared with COPD only, patients with HF plus COPD had higher levels of post-bronchodilator FEV1/FVC (median quartiles 0.57 0.47–0.64 vs 0.62 0.55–0.66 and lower total lung capacity % (115 104–126% vs 105 95–117%, P < .001) P < .001), but comparable levels of post-bronchodilator FEV1% (70 56–84% vs 68 54–80%, P = .22) and thus similar distributions of GOLD stages I–IV in both groups (24/56/19/4% vs 31/50/19/1%, P = .57). In patients with HF only, 25% exhibited pre-bronchodilator FEV1% levels of <80% (FEV1% 94 80–108%), despite a pre-bronchodilator FEV/FVC ratio ≥0.7 in this group. The reduction of FEV1 in patients with HF only was associated with HF severity. Conclusions In stable HF, FEV1 may be significantly reduced even in the absence of “real” airflow obstruction. In this situation, diagnosing COPD according to GOLD criteria (based on FEV1/FVC) still seems feasible, because both FEV1 and FVC are usually decreased to an equal extent in HF. However, classifying COPD based on FEV1 levels may overrate obstruction severity in patients with combined disease (HF plus COPD), and thus may lead to unjustified use of bronchodilators.
Background Although cardiovascular magnetic resonance imaging (CMR) is well established, its diagnostic accuracy in identifying chronic heart failure (CHF) in patients with chronic obstructive ...pulmonary disease (COPD) has not yet been quantified. Methods Participants were recruited from a cohort of 405 patients aged ≥65 years, with mild to moderate and stable COPD. In this population, 83 (20.5%) patients had a new diagnosis of CHF, all left-sided, established by an expert panel using all available diagnostic information, including echocardiography. In a nested case-control study design, 37 consecutive COPD patients with newly detected CHF (cases) and a random sample of 41 of the remaining COPD patients (controls) received additional CMR measurements. The value of CMR in diagnosing heart failure was quantified using univariable and multivariable logistic modeling in combination with area under the receiver operating characteristic curves (ROC-area). Results Combination of CMR measurements of left ventricular ejection fraction, indexed left and right atrial volume, and left ventricular end-systolic dimensions provided high added diagnostic value beyond clinical items (ROC-area 0.91) for identifying CHF. Left-sided measurements of CMR and echocardiography correlated well, including ejection fraction. Right ventricular mass divided by right ventricular end-diastolic volume was higher in COPD patients with CHF than in those without concomitant CHF. Conclusions Easily assessable morphologic and volume-based CMR measurements have excellent capacities to identify previously unknown left-sided chronic heart failure in mild to moderate COPD patients. There seems to be an adaptive tendency to concentric right ventricular hypertrophy in COPD patients with left-sided CHF.
Mortality caused by acute cardiopulmonary disease is decreasing, and in many countries the population is aging rapidly. Yet, the life-years gained are often spent with multiple chronic and slowly ...progressive conditions, and this particularly applies to patients with cardiopulmonary disease. Affected individuals often have multiple diagnoses related to the cardiopulmonary-metabolic axis with accelerated aging and gradually progressive failure of organs that provide the body with oxygen and nutrients. This more or less reflects an “engine running out of fuel.” This, for instance, is the case with the concurrent presence of COPD and heart failure in one patient that is often combined with other comorbidities such as atrial fibrillation, renal failure, or diabetes. This asks for a paradigm shift: away from single-disease-oriented patient management and toward patient-tailored multimorbidity medicine. Daily clinical practice is already recognizing this on a daily basis, yet clinical research and guidelines are still lagging behind. Thus, novel research approaches are needed to better guide evidence-based clinical practice. These approaches include the construction of diagnostic models to predict the presence of multiple diseases simultaneously, individual patient data meta-analysis as a method to examine variation in the effects of treatments or diagnostic tests depending on comorbidity, and the construction of therapeutic prediction models that predict the therapeutic effect of drugs based on the presence (or absence) of relevant comorbidity. We argue that multimorbidity should be regarded as a “friend” and not as a “foe” in clinical research addressing the current clinical problems in daily practice.
Abstract Background In patients suspected of new slow-onset heart failure, data on the comparative diagnostic performance of automated B-type natriuretic peptide (BNP) assays are scarce. Methods and ...Results Two hundred patients referred to a heart failure outpatient diagnostic facility underwent standard diagnostic work-up including echocardiography. The reference standard for the diagnosis of heart failure was an expert panel conclusion. N-terminal pro-BNP on Elecsys and BNP on Axsym and Centaur machines were measured in a single batch. Data were available for 172 patients; 51 had heart failure (29.7%). All 3 tests had high c-statistic values. An intermediate-risk subset of 111 patients (34% with heart failure) was created by excluding patients with very high or very low probability based on history and physical examination, the subgroup most in need of an additional test. Applying different thresholds for ruling heart failure in or out, the positive predicted values in this “gray zone” group were 75%, 76%, and 72%, respectively, and the negative predictive values 83%, 71%, and 85%, with the remaining 50% of patients having ∼18% probability of heart failure. Conclusion In practice, a valid diagnosis in patients suspected of slow-onset heart failure remains elusive for many in the absence of echocardiographic imaging.
Abstract Purpose Observational studies are prone to (unmeasured) confounding. Sensitivity analysis of unmeasured confounding typically focuses on a single unmeasured confounder. The purpose of this ...study was to assess the impact of multiple (possibly weak) unmeasured confounders. Methods Simulation studies were performed based on parameters estimated from the British Women's Heart and Health Study, including 28 measured confounders and assuming no effect of ascorbic acid intake on mortality. In addition, 25, 50, or 100 unmeasured confounders were simulated, with various mutual correlations and correlations with measured confounders. Results The correlated unmeasured confounders did not need to be strongly associated with exposure and outcome to substantially bias the exposure–outcome association at interest, provided that there are sufficiently many unmeasured confounders. Correlations between unmeasured confounders, in addition to the strength of their relationship with exposure and outcome, are key drivers of the magnitude of unmeasured confounding and should be considered in sensitivity analyses. However, if the unmeasured confounders are correlated with measured confounders, the bias yielded by unmeasured confounders is partly removed through adjustment for the measured confounders. Conclusions Discussions of the potential impact of unmeasured confounding in observational studies, and sensitivity analyses to examine this, should focus on the potential for the joint effect of multiple unmeasured confounders to bias results.
Abstract Background Elderly heart failure (HF) patients frequently have multiple comorbidities. The prognostic impact of combined comorbidities is poorly quantified in these patients. We assessed the ...impact of comorbidities on 3-year mortality in geriatric outpatients with newly diagnosed HF. Methods and Results Of 93 geriatric outpatients with HF (mean age 82.7 years, 36.6% men), 52 patients (55.9%) died within 3 years after HF was diagnosed. Comorbidity was measured with the Charlson Comorbidity Index (CCI). Age- and gender-adjusted hazard ratio (HR) for 3-year mortality was 1.6 (95% confidence interval CI 0.9–3.2) for patients with 3–4 CCI points and 3.2 (95% CI 1.5–6.8) for those with >4 CCI points, compared with 1–2 CCI points. After adjustment for age, gender, left ventricular ejection fraction (LVEF), and N-terminal pro–B-type natriuretic peptide, CCI remained predictive of death (CCI 3–4: HR 1.5 (95% CI 0.7–2.9); CCI >4: HR 4.0 (95% CI 1.9–8.8)). In addition to age and gender, the c-statistics for CCI and LVEF were similar (0.63 95% CI 0.55–0.70 and 0.64 95% CI 0.56–0.72, respectively). Conclusions The majority of geriatric outpatients with new HF die within 3 years. Comorbidity, summarized in the CCI, is the strongest independent predictor of mortality.
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