Differences in guideline-recommended heart failure medication between Dutch heart failure clinics: an analysis of the CHECK-HF registry

Background: Heart failure (HF) is associated with poor prognosis, high morbidity and mortality. The prognosis can be optimised by guideline adherence, which also can be used as a benchmark of quality of care. The purpose of this study was to evaluate differences in use of HF medication between Dutch HF clinics. Methods: The current analysis was part of a cross-sectional registry of 10,910 chronic HF patients at 34 Dutch outpatient clinics in the period of 2013 until 2016 (CHECK-HF), and focused on the differences in prescription rates between the participating clinics in patients with heart failure with reduced ejection fraction (HFrEF). Results: A total of 8,360 HFrEF patients were included with a mean age of 72.3 ± 11.8 years (ranging between 69.1 ± 11.9 and 76.6 ± 10.0 between the clinics), 63.9% were men (ranging between 54.3 and 78.1%), 27.3% were in New York Heart Association (NYHA) class III/IV (ranging between 8.8 and 62.1%) and the average estimated glomerular filtration rate (eGFR) was 59.6 ± 24.6 ml/min (ranging between 45.7 ± 23.5 and 97.1 ± 16.5). The prescription rates ranged from 58.9–97.4% for beta blockers (p < 0.01), 61.9–97.1% for renin-angiotensin system (RAS) inhibitors (p < 0.01), 29.9–86.8% for mineralocorticoid receptor antagonists (MRAs) (p < 0.01), 0.0–31.3% for ivabradine (p < 0.01) and 64.9–100.0% for diuretics (p < 0.01). Also, the percentage of patients who received the target dose differed significantly, 5.9–29.1% for beta blockers (p < 0.01), 18.4–56.1% for RAS inhibitors (p < 0.01) and 13.2–60.6% for MRAs (p < 0.01). Conclusions: The prescription rates and prescribed dosages of guideline-recommended medication differed significantly between HF outpatient clinics in the Netherlands, not fully explained by differences in patient profiles

Medical treatment of octogenarians with chronic heart failure: data from CHECK-HF

Background: Elderly heart failure (HF) patients are underrepresented in clinical trials, though are a large proportion of patients in real-world practice. We investigated practice-based, secondary care HF management in a large group of chronic HF patients aged ≥ 80 years (octogenarians). Methods: We analyzed electronic health records of 3490 octogenarians with chronic HF at 34 Dutch outpatient clinics in the period between 2013 and 2016 , 49% women. Study patients were divided into HFpEF [LVEF ≥ 50%; n = 911 (26.1%)], HFrEF [LVEF < 40%; n = 2009 (57.6%)] and HF with mid-range EF [HFmrEF: LVEF 40–49%; n = 570 (16.3%)]. Results: Most HFrEF patients aged ≥ 80 years received a beta blocker and a renin–angiotensin system (RAS) inhibitor (angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker), i.e. 78.3% and 72.8% respectively, and a mineralocorticoid receptor antagonist (MRA) was prescribed in 52.0% of patients. All three of these guideline-recommended medications (triple therapy) were given in only 29.9% of octogenarians with HFrEF, and at least 50% of target doses of triple therapy, beta blockers, RAS inhibitor and MRA, were prescribed in 43.8%, 62.2% and 53.5% of the total group of HFrEF patients. Contraindications or intolerance for beta blockers was present in 3.5% of the patients, for RAS inhibitors and MRAs in, 7.2% and 6.1% Conclusions: The majority of octogenarians with HFrEF received one or more guideline-recommended HF medications. However, triple therapy or target doses of the medications were prescribed in a minority. Comorbidities and reported contraindications and tolerances did not fully explain underuse of recommended HF therapies. Graphic abstract: [Figure not available: see fulltext.]

Atrial fibrillation in chronic heart failure patients with reduced ejection fraction: The CHECK-HF registry

Background: Atrial fibrillation (AF) is common in chronic heart failure (HF) patients and influences the choice and effects of drug and device therapy. In this large real-world HF registry, we studied whether the presence of AF affects the prescription of guideline-recommended HF therapy. Methods: We analyzed 8253 patients with chronic HF with reduced ejection fraction (HFrEF) from 34 Dutch outpatient clinics included in the period between 2013 and 2016 treated according to the 2012 ESC guidelines. Results: 2109 (25.6%) of these patients were in AF (mean age 76.8 ± 9.2 years, 65.0% were men) and 6.144 (74.4%) had no AF (mean age 70.7 ± 12.2 years, 63.6% were men). Patients with AF more often received beta-blockers (81.7% vs. 79.7%, p = 0.04), MRAs (57.1% vs. 51.7%, p < 0.01), diuretics (89.7% vs. 80.6%, p < 0.01) and digoxin (40.1% vs. 9.3%, p < 0.01) compared to patients without AF, whereas they less often receive renin-angiotensin-system (RAS)-inhibitors (76.1% vs. 83.1%, p < 0.01). The number of patients who received beta-blockers, RAS-inhibitor and MRA at ≥50% of the recommended target dose was comparable between those with and without AF (16.6% vs. 15.2%, p = 0.07). Conclusion: In this large cohort of chronic HFrEF patients, the prevalence of AF was high and we observed significant differences in prescription of both guideline-recommended HF between patients with and without AF

Clinical profile and contemporary management of patients with heart failure with preserved ejection fraction: results from the CHECK-HF registry

Background: Clinical management of heart failure with preserved ejection fraction (HFpEF) centres on treating comorbidities and is likely to vary between countries. Thus, to provide insight into the current management of HFpEF, studies from multiple countries are required. We evaluated the clinical profiles and current management of patients with HFpEF in the Netherlands. Methods: We included 2153 patients with HFpEF (defined as a left ventricular ejection fraction ≥ 50%) from the CHECK-HF registry, which included patients from 2013 to 2016. Results: Median age was 77 (IQR 15) years, 55% were women and the most frequent comorbidities were hypertension (51%), renal insufficiency (45%) and atrial fibrillation (AF, 38%). Patients between 65 and 80 years and those over 80 years had on average more comorbidities (up to 64% and 74%, respectively, with two or more comorbidities) than patients younger than 65 years (38% with two or more comorbidities, p-value < 0.001). Although no specific drugs are available for HFpEF, treating comorbidities is advised. Beta-blockers were most frequently prescribed (78%), followed by loop diuretics (74%), renin-angiotensin system (RAS) inhibitors (67%) and mineralocorticoid receptor antagonists (MRAs, 39%). Strongest predictors for loop-diuretic use were older age, higher New York Heart Association class and AF. Conclusion: The medical HFpEF profile is determined by the underlying comorbidities, sex and age. Comorbidities are highly prevalent in HFpEF patients, especially in elderly HFpEF patients. Despite the lack of evidence, many HFpEF patients receive regular beta-blockers, RAS inhibitors and MRAs, often for the treatment of comorbidities

The combination of carboxy-terminal propeptide of procollagen type I blood levels and late gadolinium enhancement at cardiac magnetic resonance provides additional prognostic information in idiopathic dilated cardiomyopathy - A multilevel assessment of myocardial fibrosis in dilated cardiomyopathy

Aims To determine the prognostic value of multilevel assessment of fibrosis in dilated cardiomyopathy (DCM) patients. Methods and results We quantified fibrosis in 209 DCM patients at three levels: (i) non-invasive late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR); (ii) blood biomarkers [amino-terminal propeptide of procollagen type III (PIIINP) and carboxy-terminal propeptide of procollagen type I (PICP)], (iii) invasive endomyocardial biopsy (EMB) (collagen volume fraction, CVF). Both LGE and elevated blood PICP levels, but neither PIIINP nor CVF predicted a worse outcome defined as death, heart transplantation, heart failure hospitalization, or life-threatening arrhythmias, after adjusting for known clinical predictors [adjusted hazard ratios: LGE 3.54, 95% confidence interval (CI) 1.90-6.60; P < 0.001 and PICP 1.02, 95% CI 1.01-1.03; P = 0.001]. The combination of LGE and PICP provided the highest prognostic benefit in prediction (likelihood ratio test P = 0.007) and reclassification (net reclassification index: 0.28, P = 0.02; and integrated discrimination improvement index: 0.139, P = 0.01) when added to the clinical prediction model. Moreover, patients with a combination of LGE and elevated PICP (LGE+/PICP+) had the worst prognosis (log-rank P < 0.001). RNA-sequencing and gene enrichment analysis of EMB showed an increased expression of pro-fibrotic and pro-inflammatory pathways in patients with high levels of fibrosis (LGE+/PICP+) compared to patients with low levels of fibrosis (LGE-/PICP-). This would suggest the validity of myocardial fibrosis detection by LGE and PICP, as the subsequent generated fibrotic risk profiles are associated with distinct cardiac transcriptomic profiles. Conclusion The combination of myocardial fibrosis at CMR and circulating PICP levels provides additive prognostic value accompanied by a pro-fibrotic and pro-inflammatory transcriptomic profile in DCM patients with LGE and elevated PICP

A randomised comparison of the effect of haemodynamic monitoring with CardioMEMS in addition to standard care on quality of life and hospitalisations in patients with chronic heart failure: Design and rationale of the MONITOR HF multicentre randomised clinical trial

Background: Assessing haemodynamic congestion based on filling pressures instead of clinical congestion can be a way to further improve quality of life (QoL) and clinical outcome by intervening before symptoms or weight gain occur in heart failure (HF) patients. The clinical efficacy of remote monitoring of pulmonary artery (PA) pressures (CardioMEMS; Abbott Inc., Atlanta, GA, USA) has been demonstrated in the USA. Currently, the PA sensor is not reimbursed in the European Union as its benefit when applied in addition to standard HF care is unknown in Western European countries, including the Netherlands. Aims: To demonstrate the efficacy and cost-effectiveness of haemodynamic PA monitoring in addition to contemporary standard HF care in a high-quality Western European health care system. Methods: The current study is a prospective, multi-centre, randomised clinical trial in 340 patients with chronic HF (New York Heart Association functional class III) randomised to HF care including remote monitoring with the CardioMEMS PA sensor or standard HF care alone. Eligible patients have at least one hospitalisation for HF in 12 months before enrolment and will be randomised in a 1:1 ratio. Minimum follow-up will be 1 year. The primary endpoint is the change in QoL as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ). Secondary endpoints are the number of HF hospital admissions and changes in health status assessed by EQ-5D-5L questionnaire including healt

Differences in guideline-recommended heart failure medication between Dutch heart failure clinics: an analysis of the CHECK-HF registry

Background: Heart failure (HF) is associated with poor prognosis, high morbidity and mortality. The prognosis can be optimised by guideline adherence, which also can be used as a benchmark of quality of care. The purpose of this study was to evaluate differences in use of HF medication between Dutch HF clinics. Methods: The current analysis was part of a cross-sectional registry of 10,910 chronic HF patients at 34 Dutch outpatient clinics in the period of 2013 until 2016 (CHECK-HF), and focused on the differences in prescription rates between the participating clinics in patients with heart failure with reduced ejection fraction (HFrEF). Results: A total of 8,360 HFrEF patients were included with a mean age of 72.3 ± 11.8 years (ranging between 69.1 ± 11.9 and 76.6 ± 10.0 between the clinics), 63.9% were men (ranging between 54.3 and 78.1%), 27.3% were in New York Heart Association (NYHA) class III/IV (ranging between 8.8 and 62.1%) and the average estimated glomerular filtration rate (eGFR) was 59.6 ± 24.6 ml/min (ranging between 45.7 ± 23.5 and 97.1 ± 16.5). The prescription rates ranged from 58.9–97.4% for beta blockers (p < 0.01), 61.9–97.1% for renin-angiotensin system (RAS) inhibitors (p < 0.01), 29.9–86.8% for mineralocorticoid receptor antagonists (MRAs) (p < 0.01), 0.0–31.3% for ivabradine (p < 0.01) and 64.9–100.0% for diuretics (p < 0.01). Also, the percentage of patients who received the target dose differed significantly, 5.9–29.1% for beta blockers (p < 0.01), 18.4–56.1% for RAS inhibitors (p < 0.01) and 13.2–60.6% for MRAs (p < 0.01). Conclusions: The prescription rates and prescribed dosages of guideline-recommended medication differed significantly between HF outpatient clinics in the Netherlands, not fully explained by differences in patient profiles

The combination of carboxy-terminal propeptide of procollagen type I blood levels and late gadolinium enhancement at cardiac magnetic resonance provides additional prognostic information in idiopathic dilated cardiomyopathy - A multilevel assessment of myocardial fibrosis in dilated cardiomyopathy

Aims To determine the prognostic value of multilevel assessment of fibrosis in dilated cardiomyopathy (DCM) patients. Methods and results We quantified fibrosis in 209 DCM patients at three levels: (i) non-invasive late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR); (ii) blood biomarkers [amino-terminal propeptide of procollagen type III (PIIINP) and carboxy-terminal propeptide of procollagen type I (PICP)], (iii) invasive endomyocardial biopsy (EMB) (collagen volume fraction, CVF). Both LGE and elevated blood PICP levels, but neither PIIINP nor CVF predicted a worse outcome defined as death, heart transplantation, heart failure hospitalization, or life-threatening arrhythmias, after adjusting for known clinical predictors [adjusted hazard ratios: LGE 3.54, 95% confidence interval (CI) 1.90-6.60; P < 0.001 and PICP 1.02, 95% CI 1.01-1.03; P = 0.001]. The combination of LGE and PICP provided the highest prognostic benefit in prediction (likelihood ratio test P = 0.007) and reclassification (net reclassification index: 0.28, P = 0.02; and integrated discrimination improvement index: 0.139, P = 0.01) when added to the clinical prediction model. Moreover, patients with a combination of LGE and elevated PICP (LGE+/PICP+) had the worst prognosis (log-rank P < 0.001). RNA-sequencing and gene enrichment analysis of EMB showed an increased expression of pro-fibrotic and pro-inflammatory pathways in patients with high levels of fibrosis (LGE+/PICP+) compared to patients with low levels of fibrosis (LGE-/PICP-). This would suggest the validity of myocardial fibrosis detection by LGE and PICP, as the subsequent generated fibrotic risk profiles are associated with distinct cardiac transcriptomic profiles. Conclusion The combination of myocardial fibrosis at CMR and circulating PICP levels provides additive prognostic value accompanied by a pro-fibrotic and pro-inflammatory transcriptomic profile in DCM patients with LGE and elevated PICP