Improving early diagnosis of cardiovascular disease in patients with type 2 diabetes and COPD:Protocol of the RED-CVD cluster randomised diagnostic trial

Introduction: The early stages of chronic progressive cardiovascular disease (CVD) generally cause non-specific symptoms that patients often do not spontaneously mention to their general practitioner, and are therefore easily missed. A proactive diagnostic strategy has the potential to uncover these frequently missed early stages, creating an opportunity for earlier intervention. This is of particular importance for chronic progressive CVDs with evidence-based therapies known to improve prognosis, such as ischaemic heart disease, atrial fibrillation and heart failure. Patients with type 2 diabetes or chronic obstructive pulmonary disease (COPD) are at particularly high risk of developing CVD. In the current study, we will demonstrate the feasibility and effectiveness of screening these high-risk patients with our early diagnosis strategy, using tools that are readily available in primary care, such as symptom questionnaires (to be filled out by the patients themselves), natriuretic peptide measurement and electrocardiography. Methods and analysis: The Reviving the Early Diagnosis-CVD trial is a multicentre, cluster randomised diagnostic trial performed in primary care practices across the Netherlands. We aim to include 1300 (2×650) patients who participate in a primary care disease management programme for COPD or type 2 diabetes. Practices will be randomised to the intervention arm (performing the early diagnosis strategy during the routine visits that are part of the disease management programmes) or the control arm (care as usual). The main outcome is the number of newly detected cases with CVDs in both arms, and the subsequent therapies they received. Secondary endpoints include quality of life, cost-effectiveness and the added diagnostic value of family and reproductive history questionnaires and three (novel) biomarkers (high-sensitive troponin-I, growth differentiation factor-15 and suppressor of tumourigenicity 2). Finally newly initiated treatments will be compared in both groups. Ethics and dissemination: The protocol was approved by the Medical Ethical Committee of the University Medical Center Utrecht, the Netherlands. Results are expected in 2022 and will be disseminated through international peer-reviewed publications. Trial registration number NTR7360

Proactive screening for symptoms:A simple method to improve early detection of unrecognized cardiovascular disease in primary care. Results from the Lifelines Cohort Study

Cardiovascular disease (CVD) often goes unrecognized, despite symptoms frequently being present. Proactive screening for symptoms might improve early recognition and prevent disease progression or acute cardiovascular events. We studied the diagnostic value of symptoms for the detection of unrecognized atrial fibrillation (AF), heart failure (HF), and coronary artery disease (CAD) and developed a corresponding screening questionnaire. We included 100,311 participants (mean age 52 ± 9 years, 58% women) from the population-based Lifelines Cohort Study. For each outcome (unrecognized AF/HF/CAD), we built a multivariable model containing demographics and symptoms. These models were combined into one 'three-disease' diagnostic model and questionnaire for all three outcomes. Results were validated in Lifelines participants with chronic obstructive pulmonary disease (COPD) and diabetes mellitus (DM). Unrecognized CVD was identified in 1325 participants (1.3%): AF in 131 (0.1%), HF in 599 (0.6%), and CAD in 687 (0.7%). Added to age, sex, and body mass index, palpitations were independent predictors for unrecognized AF; palpitations, chest pain, dyspnea, exercise intolerance, health-related stress, and self-expected health worsening for unrecognized HF; smoking, chest pain, exercise intolerance, and claudication for unrecognized CAD. Area under the curve for the combined diagnostic model was 0.752 (95% CI 0.737-0.766) in the total population and 0.757 (95% CI 0.734-0.781) in participants with COPD and DM. At the chosen threshold, the questionnaire had low specificity, but high sensitivity. In conclusion, a short questionnaire about demographics and symptoms can improve early detection of CVD and help pre-select people who should or should not undergo further screening for CVD

Integration of a palliative approach into heart failure care: a European Society of Cardiology Heart Failure Association position paper

The Heart Failure Association of the European Society of Cardiology has published a previous position paper and various guidelines over the past decade recognizing the value of palliative care for those affected by this burdensome condition. Integrating palliative care into evidence-based heart failure management remains challenging for many professionals, as it includes the identification of palliative care needs, symptom control, adjustment of drug and device therapy, advance care planning, family and informal caregiver support, and trying to ensure a 'good death'. This new position paper aims to provide day-to-day practical clinical guidance on these topics, supporting the coordinated provision of palliation strategies as goals of care fluctuate along the heart failure disease trajectory. The specific components of palliative care for symptom alleviation, spiritual and psychosocial support, and the appropriate modification of guideline-directed treatment protocols, including drug deprescription and device deactivation, are described for the chronic, crisis and terminal phases of heart failure

Heart failure in COPD

The main aim of the thesis was to assess the prevalence of heart failure in patients with a diagnosis of chronic obstructive pulmonary disease (COPD). Furthermore, to explore diagnostic strategies (including natriuretic peptides and cardiovascular magnetic resonance imaging (CMR)) to identify heart failure in COPD patients. Finally, to document common mechanisms and possible interactions in the development of the two syndromes. The prevalence of previously unknown heart failure was assessed in 405 patients ≥ 65 years with a GP diagnosis of COPD, in a stable phase of their disease. All participants underwent an extensive systematic diagnostic work-up and an expert panel established the presence of heart failure and/or COPD during consensus meetings. Of 405 participating patients with a diagnosis of COPD, 83 (20.5%) had previously unrecognised heart failure (42 patients systolic, and 41 'isolated' diastolic, and none 'isolated' right sided heart failure). In total 244 (60.2%) patients had COPD according to the GOLD criteria; in 50 (20.5%) patients combined with unrecognised heart failure. The prevalence of heart failure in stable COPD patients is therefore about four times as high as in subjects aged 65 years or over in the population at large. Independent clinical determinants of the presence of concomitant heart failure were a history of ischaemic heart disease, body mass index, laterally displaced apex beat, and heart rate. The ROC-area of this multivariate 'clinical model' with these four predictors was 0.70. The ROC area of amino-terminal pro B-type natriuretic peptide (NT-proBNP) as a single test was 0.72. Addition of NT-proBNP to the 'clinical model' significantly increased the ROC-area to 0.77 (95% CI 0.71-0.83). Addition of electrocardiography to the 'clinical model' increased the ROC-area to 0.75 (95% CI 0.69-0.81). Thus, a limited number of easy available items from history and physical examination with addition of NT-proBNP and/or electrocardiography can increase the confidence of the clinician about the presence or absence of concomitant heart failure in patients with stable COPD. In a nested-case control study we assessed the diagnostic value of cardiovascular magnetic resonance (CMR) imaging for detecting or excluding heart failure in COPD patients. The diagnostic value of CMR was higher than that of electrocardiography or natriuretic peptide measurements. CMR may serve as an alternative in case of uninterpretable echocardiographic results. We reviewed the literature for etiological and pathophysiological pathways that could be involved in the development of heart failure in the presence of COPD or vice versa. The relationship between COPD and heart failure seems multi-factorial, with tobacco smoking as a common etiologic factor. Local and systemic inflammation, and possibly local and systemic atherosclerosis are common pathways. An important starting point for both diseases seems to be dysfunction of the alveolar-capillary membrane, resulting in decreased oxygen diffusion, and (in more severe cases) sympathetic and structural changes in heart and lungs, which could promote the development of COPD and heart failure. At the moment, much of the interrelation between both syndromes is still unknown. Conclusion: Clinicians should be aware of the high prevalence of previously unknown heart failure in elderly patients with COPD. Intensified co-operation between general practitioners, pulmonologists and cardiologists is needed in clinical practice and research to extend the diagnostic strategies, further explore common pathways and treatment options, and eventually increase the prognosis of this large patient population

Are there gender disparities in symptom presentation or triage of patients with chest discomfort at primary care out-of-hours services? : An observational study

OBJECTIVES: Previous hospital-based studies have suggested delayed recognition of acute coronary syndrome (ACS) in women. We wanted to assess differences in symptom presentation or triage among women and men who contacted primary care out-of-hours services (OHS) for chest discomfort. DESIGN: Retrospective observational study. SETTING: Primary care OHS. PARTICIPANTS: 276 women and 242 men with chest discomfort who contacted a primary care OHS in the Netherlands in 2013 and 2014. MAIN OUTCOME MEASURES: Differences between women and men regarding symptom presentation and urgency allocation. RESULTS: 8.4% women and 14.0% men had ACS. Differences in symptoms between patients with and without ACS were in general small, for both women and men. In women with ACS compared with women without ACS, mean duration of telephone calls was discriminative; 5.22 (SD 2.53) vs 7.26 (SD 3.11) min, p value=0.003. In men, radiation of pain (89.3% vs 54.9%, p value=0.011) was discriminative for ACS, and stabbing chest pain (3.7% vs 24.0%, p value=0.014) for absence of ACS . Women and men with chest discomfort received similar high urgency allocation (crude and adjusted OR after correction for ACS and age; 1.03 (95% CI 0.72 to 1.48) and 1.04 (95% CI 0.72 to 1.52), respectively). Women with ACS received a high urgency allocation in 22/23 (95.7%) and men with ACS in 30/34 (88.2%), p value=0.331. CONCLUSIONS: Discriminating ACS in patients with chest discomfort who contacted primary care OHS is difficult in both women and men. Women and men with chest discomfort received similar high urgency allocation

Are there gender disparities in symptom presentation or triage of patients with chest discomfort at primary care out-of-hours services? An observational study

Objectives Previous hospital-based studies have suggested delayed recognition of acute coronary syndrome (ACS) in women. We wanted to assess differences in symptom presentation or triage among women and men who contacted primary care out-of-hours services (OHS) for chest discomfort. Design Retrospective observational study. Setting Primary care OHS. Participants 276 women and 242 men with chest discomfort who contacted a primary care OHS in the Netherlands in 2013 and 2014. Main outcome measures Differences between women and men regarding symptom presentation and urgency allocation. Results 8.4% women and 14.0% men had ACS. Differences in symptoms between patients with and without ACS were in general small, for both women and men. In women with ACS compared with women without ACS, mean duration of telephone calls was discriminative; 5.22 (SD 2.53) vs 7.26 (SD 3.11) min, p value=0.003. In men, radiation of pain (89.3% vs 54.9%, p value=0.011) was discriminative for ACS, and stabbing chest pain (3.7% vs 24.0%, p value=0.014) for absence of ACS. Women and men with chest discomfort received similar high urgency allocation (crude and adjusted OR after correction for ACS and age; 1.03 (95% CI 0.72 to 1.48) and 1.04 (95% CI 0.72 to 1.52), respectively). Women with ACS received a high urgency allocation in 22/23 (95.7%) and men with ACS in 30/34 (88.2%), p value=0.331. Conclusions Discriminating ACS in patients with chest discomfort who contacted primary care OHS is difficult in both women and men. Women and men with chest discomfort received similar high urgency allocation

Cost-effectiveness of screening strategies to detect heart failure in patients with type 2 diabetes

Background: Heart failure (HF), especially with preserved ejection fraction (HFpEF) is common in older patients with type 2 diabetes (T2DM), but often not recognized. Early HF detection in older T2DM patients may be worthwhile because treatment may be initiated in an early stage, with clear beneficial treatment in those with reduced ejection fraction (HFrEF), but without clear prognostic beneficial treatment in those with HFpEF. Because both types of HF may be uncovered in older T2DM, screening may improve health outcomes at acceptable costs. We assessed the cost-effectiveness of five screening strategies in patients with T2DM aged 60years or over. Methods: We built a Markov model with a lifetime horizon based on the prognostic results from our screening study of 581 patients with T2DM, extended with evidence from literature. Cost-effectiveness was calculated from a Dutch healthcare perspective as additional costs (Euros) per additional quality-adjusted life-year (QALY) gained. We performed probabilistic sensitivity analysis to assess robustness of these outcomes. Scenario analyses were performed to assess the influence of the availability of effective treatment of heart failure with preserved ejection fraction. Results: For willingness to pay values in the range of €6050/QALY-€31,000/QALY for men and €6300/QALY-€42,000/QALY for women, screening-based checking the electronic medical record for patient characteristics and medical history plus the assessment of symptoms had the highest probability of being cost-effective. For higher willingness-to-pay values, direct echocardiography was the preferred screening strategy. Cost-effectiveness of all screening strategies improved with the increase in effectiveness of treatment for HFpEF. Conclusions: Screening forHF in older community-dwelling patients with T2DM is cost-effective at the commonly used willingness-to-pay threshold of €20.000/QALY by checking the electronic medical record for patient characteristics and medical history plus the assessment of symptoms. The simplicity of such a strategy makes it feasible for implementation in existing primary care diabetes management programs

Proactive screening for symptoms: A simple method to improve early detection of unrecognized cardiovascular disease in primary care. Results from the Lifelines Cohort Study

Cardiovascular disease (CVD) often goes unrecognized, despite symptoms frequently being present. Proactive screening for symptoms might improve early recognition and prevent disease progression or acute cardiovascular events. We studied the diagnostic value of symptoms for the detection of unrecognized atrial fibrillation (AF), heart failure (HF), and coronary artery disease (CAD) and developed a corresponding screening questionnaire. We included 100,311 participants (mean age 52 ± 9 years, 58% women) from the population-based Lifelines Cohort Study. For each outcome (unrecognized AF/HF/CAD), we built a multivariable model containing demographics and symptoms. These models were combined into one ‘three-disease’ diagnostic model and questionnaire for all three outcomes. Results were validated in Lifelines participants with chronic obstructive pulmonary disease (COPD) and diabetes mellitus (DM). Unrecognized CVD was identified in 1325 participants (1.3%): AF in 131 (0.1%), HF in 599 (0.6%), and CAD in 687 (0.7%). Added to age, sex, and body mass index, palpitations were independent predictors for unrecognized AF; palpitations, chest pain, dyspnea, exercise intolerance, health-related stress, and self-expected health worsening for unrecognized HF; smoking, chest pain, exercise intolerance, and claudication for unrecognized CAD. Area under the curve for the combined diagnostic model was 0.752 (95% CI 0.737–0.766) in the total population and 0.757 (95% CI 0.734–0.781) in participants with COPD and DM. At the chosen threshold, the questionnaire had low specificity, but high sensitivity. In conclusion, a short questionnaire about demographics and symptoms can improve early detection of CVD and help pre-select people who should or should not undergo further screening for CVD

Obstructive pulmonary disease and the risk of sudden cardiac arrest stratified by age group, sex and cardiovascular risk profile¹.

<p>Data are number (%). CI: confidence interval, CVD: cardiovascular disease, N: number, n/a: not applicable, OPD: obstructive pulmonary disease, OR: odds ratio.</p>1<p>Use of β- adrenoreceptor blockers, calcium channel antagonists, angiotensin converting enzyme inhibitors, diuretics, angiotensin-II receptor blockers, nitrates, platelet aggregation inhibitors, and/or statins within six months prior to index date.</p>2<p>Adjusted for cardiovascular risk profile.</p>3<p>Interaction on a multiplicative scale: OR 1.1 (0.7–1.6), on an additive scale: synergy index 1.4 (0.7–2.6).</p