Heart failure medication dosage and survival in women and men seen at outpatient clinics.

OBJECTIVE: Women with heart failure with reduced ejection fraction (HFrEF) may reach optimal treatment effect at half of the guideline-recommended medication dose. This study investigates prescription practice and its relation with survival of patients with HF in daily care. METHODS: Electronic health record data from 13 Dutch outpatient cardiology clinics were extracted for HF receiving at least one guideline-recommended HF medication. Dose changes over consecutive prescriptions were modelled using natural cubic splines. Inverse probability-weighted Cox regression was used to assess the relationship between dose (reference≥50% target dose) and all-cause mortality. RESULTS: The study population comprised 561 women (29% HFrEF (ejection fraction (EF)<40%), 49% heart failure with preserved ejection fraction (EF≥50%); HFpEF and 615 men (47% and 25%, respectively). During a median follow-up of 3.7 years, 252 patients died (48% women; 167 HFrEF, 84 HFpEF). Nine hundred thirty-four patients (46% women) received ACE inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), 795 (48% women) beta blockers and 178 (42% women) mineralocorticoid receptor antagonists (MRAs). In both sexes, the mean target dose across prescriptions was 50% for ACEI/ARBs and beta blockers, and 100% for MRAs. ACEI/ARB dose of <50% was associated with lower mortality in women but not in men with HFrEF. This was not seen in patients with HFpEF. Beta-blocker dose was not associated with all-cause mortality. CONCLUSION: Patients with HF seen in outpatient cardiology clinics receive half of the guideline-recommended medication dose. Lower ACEI/ARB dose was associated with improved survival in women with HFrEF. These results underscore the importance of (re)defining optimal medical therapy for women with HFrEF.

Cardiovascular imaging of women and men visiting the outpatient clinic with chest pain or discomfort: design and rationale of the ARGUS Study.

INTRODUCTION: Chest pain or discomfort affects 20%-40% of the general population over the course of their life and may be a symptom of myocardial ischaemia. For the diagnosis of obstructive macrovascular coronary artery disease (CAD), algorithms have been developed; however, these do not exclude microvascular angina. This may lead to false reassurance of symptomatic patients, mainly women, with functionally significant, yet non-obstructive coronary vascular disease. Therefore, this study aims to estimate the prevalence of both macrovascular and microvascular coronary vascular disease in women and men presenting with chest pain or discomfort, and to subsequently develop a decision-support tool to aid cardiologists in referral to cardiovascular imaging for both macrovascular and microvascular CAD evaluation. METHODS AND ANALYSIS: Women and men with chest pain or discomfort, aged 45 years and older, without a history of cardiovascular disease, who are referred to an outpatient cardiology clinic by their general practitioner are eligible for inclusion. Coronary CT angiography is used for anatomical imaging. Additionally, myocardial perfusion imaging by adenosine stress cardiac MRI is performed to detect functionally significant coronary vascular disease. Electronic health record data, collected during regular cardiac work-up, including medical history, cardiovascular risk factors, physical examination, echocardiography, (exercise) ECG and blood samples for standard cardiovascular biomarkers and research purposes, are obtained. Participants will be classified as positive or negative for coronary vascular disease based on all available data by expert panel consensus (a cardiovascular radiologist and two cardiologists). After completion of the clinical study, all collected data will be used to develop a decision support tool using predictive modelling and machine-learning techniques. ETHICS AND DISSEMINATION: The study protocol was approved by the Institutional Review Board of the University Medical Center Utrecht. Results will be disseminated through national and international conferences and in peer-reviewed journals in cardiovascular disease. TRIAL REGISTRATION NUMBER: Trialregister.nl Registry NL8702.

Coronary artery disease prediction in women and men using chest pain characteristics and risk factors: an observational study in outpatient clinics.

OBJECTIVES: To assess the diagnostic value of non-acute chest pain characteristics for coronary artery disease in women and men referred to outpatient cardiology clinics. DESIGN AND SETTING: This is an observational study performed at outpatient cardiology centres of the Netherlands. PARTICIPANTS: The study population consisted of 1028 patients with non-acute chest pain (505 women). ANALYSIS AND RESULTS: Twenty-four women (5%) and 75 men (15%) were diagnosed with coronary artery disease by invasive coronary angiography or CT angiography during regular care follow-up. Elastic net regression was performed to assess which chest pain characteristics and risk factors were of diagnostic value. The overall model selected age, provocation by temperature or stress, relief at rest and functional class as determinants and was accurate in both sexes (area under the curve (AUC) of 0.76 (95% CI 0.68 to 0.85) in women and 0.83 (95% CI 0.78 to 0.88) in men). Both sex-specific models selected age, pressuring nature, radiation, duration, frequency, progress, provocation and relief at rest as determinants. The female model additionally selected dyspnoea, body mass index, hypertension and smoking while the male model additionally selected functional class and diabetes. The sex-specific models performed better than the overall model, but more so in women (AUC: 0.89, 95% CI 0.81 to 0.96) than in men (AUC: 0.84, 95% CI 0.73 to 0.90). CONCLUSIONS: In both sexes, the diagnostic value of non-acute chest pain characteristics and risk factors for coronary artery disease was high. Provocation, relief at rest and functional class of chest pain were the most powerful diagnostic predictors in both women and men. When stratified by sex the performance of the model improved, mostly in women.