Pulmonary artery pressure monitoring in chronic heart failure: effects across clinically relevant subgroups in the MONITOR-HF trial.

BACKGROUND AND AIMS: In patients with chronic heart failure (HF), the MONITOR-HF trial demonstrated the efficacy of pulmonary artery (PA)-guided HF therapy over standard of care in improving quality of life and reducing HF hospitalizations and mean PA pressure. This study aimed to evaluate the consistency of these benefits in relation to clinically relevant subgroups. METHODS: The effect of PA-guided HF therapy was evaluated in the MONITOR-HF trial among predefined subgroups based on age, sex, atrial fibrillation, diabetes mellitus, left ventricular ejection fraction, HF aetiology, cardiac resynchronisation therapy, and implantable cardioverter defibrillator. Outcome measures were based upon significance in the main trial and included quality of life, clinical, and PA pressure endpoints, and were assessed for each subgroup. Differential effects in relation to the subgroups were assessed with interaction terms. Both unadjusted and multiple testing adjusted interaction terms were presented. RESULTS: The effects of PA monitoring on quality of life, clinical events, and PA pressure were consistent in the predefined subgroups, without any clinically relevant heterogeneity within or across all endpoint categories (all adjusted interaction P-values were nonsignificant). In the unadjusted analysis of the primary endpoint quality-of-life change, weak trends towards a less pronounced effect in older patients (Pinteraction = 0.03; adjusted Pinteraction = 0.33) and diabetics (Pinteraction = 0.01; adjusted Pinteraction = 0.06) were observed. However, these interaction effects did not persist after adjusting for multiple testing. CONCLUSIONS: This subgroup analysis confirmed the consistent benefits of PA-guided HF therapy observed in the MONITOR-HF trial across clinically relevant subgroups, highlighting its efficacy in improving quality of life, clinical, and PA pressure endpoints in chronic HF patients.

The effects of positive psychology interventions on well-being and distress in patients with cardiovascular diseases: A systematic review and Meta-analysis.

OBJECTIVE: Positive psychology interventions (PPIs) have been found to be effective for psychiatric and somatic disorders. However, a systematic review and meta-analysis of studies examining the effectiveness of PPIs for patients with cardiovascular disease (CVD) is lacking. This systematic review and meta-analysis aims to synthesize studies examining the effectiveness of PPIs and to examine their effects on mental well-being and distress using meta-analyses. METHODS: This study was preregistered on OSF (https://osf.io/95sjg/). A systematic search was performed in PsycINFO, PubMed and Scopus. Studies were included if they examined the effectiveness of PPIs on well-being for patients with CVD. Quality assessment was based on the Cochrane tool for assessing risk of bias. Three-level mixed-effects meta-regression models were used to analyze effect sizes of randomized controlled trials (RCTs). RESULTS: Twenty studies with 1222 participants were included, of which 15 were RCTs. Included studies showed high variability in study and intervention characteristics. Meta-analyses showed significant effects for mental well-being (ß = 0.33) and distress (ß = 0.34) at post-intervention and the effects were still significant at follow-up. Five of the 15 RCTs were classified as having fair quality, while the remaining had low quality. CONCLUSION: These results suggest that PPIs are effective in improving well-being and distress in patients with CVD and could therefore be a valuable addition for clinical practice. However, there is a need for more rigorous studies that are adequately powered and that help us understand what PPIs are most effective for which patient.

Heart failure treatment in patients with and without obesity with an ejection fraction below 50.

BACKGROUND: The aim of this study was to assess heart failure (HF) treatment in patients with and without obesity in a large contemporary real-world Western European cohort. METHODS: Patients with a left ventricular ejection fraction (LVEF) <50% and available information on body mass index (BMI) were selected from the CHECK-HF registry. The CHECK-HF registry included chronic HF patients in the period between 2013 and 2016 in 34 Dutch outpatient clinics. Patients were divided into BMI categories. Differences in HF medical treatment were analysed, and multivariable logistic regression analysis (dichotomized as BMI <30 kg/m2 and ≥30 kg/m2 ) was performed. RESULTS: Seven thousand six hundred seventy-one patients were included, 1284 (16.7%) had a BMI ≥30 kg/m2 , and 618 (8.1%) had a BMI ≥35 kg/m2 . Median BMI was 26.4 kg/m2 . Patients with obesity were younger and had a higher rate of comorbidities such as diabetes mellitus, hypertension and obstructive sleep apnoea (OSAS). Prescription rates of guideline-directed medical therapy (GDMT) increased significantly with BMI. The differences were most pronounced for mineralocorticoid receptor antagonists (MRAs) and diuretics. Patients with obesity more often received the guideline-recommended target dose. In multivariable logistic regression, obesity was significantly associated with a higher likelihood of receiving ≥100% of the guideline-recommended target dose of beta-blockers (OR 1.34, 95% CI 1.10-1.62), renin-angiotensin system (RAS)-inhibitors (OR 1.34, 95% CI 1.15-1.57) and MRAs (OR 1.40, 95% CI 1.04-1.87). CONCLUSIONS: Guideline-recommended HF drugs are more frequently prescribed and at a higher dose in patients with obesity as compared to HF patients without obesity.

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.

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.

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 health care utilisation and formal cost-effectiveness analysis. CONCLUSION: The MONITOR HF trial will evaluate the efficacy and cost-effectiveness of haemodynamic monitoring by CardioMEMS in addition to standard HF care in patients with chronic HF. Clinical Trial Registration number NTR7672.

A comparison of the prognostic value of BNP versus NT-proBNP after hospitalisation for heart failure.

AIMS: Concentrations of circulating B­type natriuretic peptides provide important prognostic information in heart failure (HF) patients. We directly compared the prognostic performance of brain natriuretic peptide (BNP) versus N­terminal-proBNP (NT-proBNP) measurements in a large population of HF patients at hospital discharge after an admission for decompensated HF. METHODS AND RESULTS: BNP and NT-proBNP were measured in 563 stable HF patients before discharge. All patients were followed for a fixed period of 18 months. The primary endpoint was time to first major event (HF hospitalisation or death). Patients were in NYHA class II (47%) or III/IV (53%) at discharge and the mean age of the patients was 71 ± 11 years, 217 (39%) females, mean left ventricular ejection fraction was 0.32 ± 0.14 and 234 (42%) had an ischaemic aetiology of HF. During the study, 236 patients (42%) reached the primary endpoint. Multivariate odds ratios of the primary endpoint for doubling of baseline levels of BNP and NT-proBNP were 1.46 (95% CI 1.19-1.80, p < 0.001) and 1.45 (95% CI 1.18-1.78, p < 0.001), respectively. The multivariable adjusted areas under the receiver-operating characteristic curve for prediction of the primary endpoint for doubling of BNP and NT-proBNP were 0.69 and 0.68, respectively. Direct comparison of the prognostic value of BNP and NT-proBNP did not reveal significant differences. CONCLUSIONS: BNP and NT-proBNP at discharge for hospitalisation for HF are powerful, and equally strong and independent predictors of all-cause death and HF rehospitalisation.

Real-world heart failure management in 10,910 patients with chronic heart failure in the Netherlands : Design and rationale of the Chronic Heart failure ESC guideline-based Cardiology practice Quality project (CHECK-HF) registry.

AIMS: Data from patient registries give insight into the management of patients with heart failure (HF), but actual data from unselected real-world HF patients are scarce. Therefore, we performed a cross sectional study of current HF care in the period 2013-2016 among more than 10,000 unselected HF patients at HF outpatient clinics in the Netherlands. METHODS: In 34 participating centres, all 10,910 patients with chronic HF treated at cardiology centres were included in the CHECK-HF registry. Of these, most (96%) were managed at a specific HF outpatient clinic. Heart failure was typically diagnosed according to the ESC guidelines 2012, based on signs, symptoms and structural and/or functional cardiac abnormalities. Information on diagnostics, treatment and co-morbidities were recorded, with specific focus on drug therapy and devices. In our cohort, the mean age was 73 years (SD 12) and 60% were male. Frequent co-morbidities reported in the patient records were diabetes mellitus 30%, hypertension 43%, COPD 19%, and renal insufficiency 58%. In 47% of the patients, ischaemia was the origin of HF. In our registry, the prevalence of HF with preserved ejection fraction was 21%. CONCLUSION: The CHECK-HF registry will provide insight into the current, real world management of patient with chronic HF, including HF with reduced ejection fraction, preserved ejection fraction and mid-range ejection fraction, that will help define ways to improve quality of care. Drug and device therapy and guideline adherence as well as interactions with age, gender and co-morbidities will receive specific attention.

Design and methodology of the COACH-2 (Comparative study on guideline adherence and patient compliance in heart failure patients) study: HF clinics versus primary care in stable patients on optimal therapy.

BACKGROUND: Since the number of heart failure (HF) patients is still growing and long-term treatment of HF patients is necessary, it is important to initiate effective ways for structural involvement of primary care services in HF management programs. However, evidence on whether and when patients can be referred back to be managed in primary care is lacking. AIM: To determine whether long-term patient management in primary care, after initial optimisation of pharmacological and non-pharmacological treatment in a specialised HF clinic, is equally effective as long-term management in a specialised HF clinic in terms of guideline adherence and patient compliance. METHOD: The study is designed as a randomised, controlled, non-inferiority trial. Two-hundred patients will be randomly assigned to be managed and followed in primary care or in a HFclinic. Patients are eligible to participate if they are (1) clinically stable, (2) optimally up-titrated on medication (according to ESC guidelines) and, (3) have received optimal education and counselling on pre-specified issues regarding HF and its treatment. Furthermore, close cooperation between secondary and primary care in terms of back referral to or consultation of the HF clinic will be provided.The primary outcome will be prescriber adherence and patient compliance with medication after 12 months. Secondary outcomes measures will be readmission rate, mortality, quality of life and patient compliance with other lifestyle changes. EXPECTED RESULTS: The results of the study will add to the understanding of the role of primary care and HF clinics in the long-term follow-up of HF patients.

TWENTE Study: The Real-World Endeavor Resolute Versus Xience V Drug-Eluting Stent Study in Twente: study design, rationale and objectives.

Background. New-generation drug-eluting stents (DES) may solve several problems encountered with first-generation DES, but there is a lack of prospective head-to-head comparisons between new-generation DES. In addition, the outcome of regulatory trials may not perfectly reflect the outcome in 'real world' patients.Objectives. To compare the efficacy and safety of two new-generation DES in a 'real world' patient population.Methods. A prospective, randomised, single-blinded clinical trial to evaluate clinical outcome after Endeavor Resolute vs. Xience V stent implantation. The primary endpoint is target vessel failure at one-year follow-up. In addition, the study comprises a two-year and an open-label five-year follow-up. (Neth Heart J 2010;18:360-4.).

Influence of renal dysfunction on the pharmacokinetics of the selective Na+/H+ exchange inhibitor EMD 87 580 in patients with chronic heart failure.

BACKGROUND: Chronic heart failure (CHF) is a potential indication for the administration of EMD 87 580, a selective Na+/H+ exchange inhibitor. CHF is often accompanied by renal dysfunction, which is known to affect the pharmacokinetics of compounds predominately cleared by the kidneys. We examined the influence of renal dysfunction on the pharmacokinetics of EMD 87 580 in patients with CHF. METHODS: 21 patients with CHF and normal renal function (Group 1) and 9 patients with CHF and renal dysfunction (Group 2) received EMD 87 580 orally over 8 days. The mean creatinine clearance (CrCl) in Group 1 was 99.7 ml/min. 12 patients in this group were randomized to receive two doses of EMD 87 580 (7 patients 2 x 50 mg and 5 patients 2 x 100 mg). The 9 patients in Group 2 with renal dysfunction (mean CrCl = 49.5 ml/min) received 50 mg EMD 87 580 once daily. Plasma and urine samples were collected for pharmacokinetic assessment. RESULTS: In CHF patients with renal dysfunction EMD 87 580 clearance was reduced to approximately 50% compared to Group 1, i.e. 6.80 ml/min (4.89-11.60) vs. 12.73 ml/min (8.93-22.21), p < 0.05, for the 50 mg dose and 14.08 ml/min (9.96-18.10), p < 0.05, for the 100 mg dose. Consequently, plasma concentrations were increased in patients with renal dysfunction; AUC0-infinity 7,354 ng/ml x h (4,311-10,232) vs. 3,928 ng/ml x h (2,251-5,596, 50 mg dose, p < 0.05). A significant correlation was observed between EMD 87 580 plasma clearance and CrCl (r2 = 0.8062). CONCLUSION: In CHF patients with renal dysfunction EMD 87 580, clearance is reduced and plasma concentrations increased. Therefore, dose adjustments for EMD 87 580 are indicated in patients with CHF and renal dysfunction.

The Na(+)/H(+) exchange inhibitor eniporide as an adjunct to early reperfusion therapy for acute myocardial infarction. Results of the evaluation of the safety and cardioprotective effects of eniporide in acute myocardial infarction (ESCAMI) trial.

OBJECTIVES: We conducted an international, prospective, randomized, double-blind, placebo-controlled phase 2 trial in patients undergoing thrombolytic therapy or primary angioplasty for acute ST-elevation myocardial infarction (MI) to investigate the effect of eniporide on infarct size and clinical outcome. BACKGROUND: Experimental studies suggest that the activity of the Na(+)/H(+) exchange (NHE) plays an important role in the unfavorable sequels of myocardial ischemia and reperfusion. Eniporide specifically inhibits the NHE-1 isoform and has been shown to limit infarct size in experimental models. METHODS: The primary efficacy end point was the infarct size measured by the cumulative release of alpha-hydroxybutyrate dehydrogenase (alpha-HDBH) (area under the curve [AUC] 0 to 72 h). In stage 1, 50, 100, 150 or 200 mg eniporide given as a 10-min infusion before start of reperfusion therapy were compared with placebo in 430 patients, and in stage 2, 100 and 150 mg eniporide were compared with placebo in 959 patients. RESULTS: In stage 1, the administration of 100 mg and 150 mg eniporide resulted in smaller infarct sizes (mean alpha-HBDH AUC in U/ml x h, placebo: 44.2, 100 mg eniporide: 40.2, 150 mg eniporide: 33.9), especially in the angioplasty group. In contrast, in stage 2 there was no difference in the enzymatic infarct size between the three groups (placebo: 41.2, 100 mg eniporide: 43.0, 150 mg eniporide: 41.5). Overall there was no effect of eniporide on clinical outcome (death, cardiogenic shock, heart failure, life-threatening arrhythmias). However, there was a significant reduction of the incidence of heart failure in patients reperfused late (>4 h). CONCLUSIONS: In this large study administration of the NHE-1 inhibitor eniporide, before reperfusion therapy in patients with acute ST elevation MI, did not limit infarct size or improve clinical outcome.

The spectrum of death after myocardial infarction: a necropsy study.

To determine the relative frequency of the causes of death in the acute (less than 24 hours), early (24 hours to 3 weeks), and chronic (greater than 3 weeks) phases of myocardial infarction, data from all autopsies performed at a university hospital during a 56-month period were reviewed. Autopsies were performed in 56% of in-hospital deaths and 27% of patients dead on arrival in the emergency room (out-of-hospital deaths). In 271 cases of suspected cardiac death, a myocardial infarction of any age was identified. Death had occurred in the acute phase of a first infarction in 19 patients and was most frequently due to pump failure (37%) followed by cardiac rupture (26%) and arrhythmias (21%). Death had occurred 24 hours to 3 weeks after a first infarction in 80 patients and was most frequently due to pump failure (44%), rupture (27%), and arrhythmias (16%). Recurrent acute infarction was found in 32% of patients whose deaths were due to arrhythmias or pump failure and in 19% of those whose deaths were due to rupture. Death had occurred greater than 3 weeks after a first infarction in 172 patients. In 132 (77%) of these patients death was due to a complication of a new acute or recent infarction. Myocardial rupture was a less frequent cause of death in patients with recurrent infarction (8%) than in those dying in the acute or early phase after their first infarction (27%, p = 0.0009). A primary arrhythmia in the absence of recurrent infarction or ischemia accounted for only 14% of out-of-hospital deaths late after an infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Monitoring of blood coagulation in open heart surgery. I. Effects of conventional dosages of heparin and protamine.

In twenty unselected patients coming for surgery with cardio-pulmonary by-pass coagulation studies were performed. Laboratory results before and after by-pass were compared with serial measurements of ACtivated Clotting Times (ACT) during and after operation using conventional dosages of heparin and protamine. Values of ACT's are presented and compared with a previously published protocol according to Bull (1). Monitoring of ACT during operation was found to be easily applicable and highly desirable. Overdosage of both heparin and protamine was suggested as a correctable cause of proven abnormal coagulation after cardio-pulmonary by-pass.

Monitoring of blood coagulation in open heart surgery. II. Use of individualized dosages of heparin and protamine controlled by activated coagulation times.

Results are presented of individualized anticoagulatory management during open heart surgery in two groups of 20 patients comparing colloid versus non-colloid priming of the extracorporeal circuit. Advantages of individualized dosages of heparin according to a constructed dose response curve and controlled by measuring Activated Coagulation Times (ACT) were safer adaptation to individual variability in heparin sensitivity, reduction of incremental heparin doses during cardiopulmonary by-pass and nearly 50% reduction of protamine dosage as compared to conventional heparinprotamin protocols. No significant influence of the type of priming used in the extracorporeal circuit on coagulatory behaviour could be detected.

Monitoring of blood oxygen tension during and after anesthesia with a bed-side PO2 meter.

Monitoring of the state of oxygenation of surgical patients during and after anesthesia has been a problem of increasing interest, especially in those cases in which clinical judgment of skin colour alone is unreliable. Therefore a clinical trial is described with a bed-side PO2-measuring device. Results of duplo measurements in arterial blood samples show good correlation with laboratory control values. It is concluded that--if periodically checked by a laboratory apparatus -- the PO2 bed-side analyser could be an useful instrument for semicontinuous monitoring of blood PO2 during anesthesia and in recovery room and intensive care unit.

Aortocoronary graft flow and reactive hyperaemia in relation to postoperative myocardial infarction.

Blood flow through aortocoronary venous grafts and its response to a brief period of arterial occlusion--reactive hyperaemia--were studied in relation to the development of postoperative myocardial infarction. In 40 patients with intractable angina due to obstructive coronary artery disease, 72 aortocoronary venous grafts were constructed. In 18% of the grafts there was no response to the flow to temporary occlusion, due to absence of reactive hyperaemia. In the remaining grafts the flow increased from 17% to 26%. In 17-5% of the patients postoperative myocardial infarction was diagnosed. No relation could be established between this control flow through aortocoronary grafts and postoperative myocardial infarction. A significant difference was found in the magnitude of the reactive hyperaemia following occlusion of the graft between patients who developed myocardial infarction (13-0%) and those who did not (26-8%). Some of our observations suggest that the myocardium is in a state of reactive hyperaemia after coronary surgery. With certain technical precautions the flow changes caused by reactive hyperaemia can be used as an indicator of the result to be expected from bypass surgery.

General and/or regional anesthesia for vascular surgery. A retrospective evaluation.

Two hundred sixty three patients for extrathoracic vascular surgery of the arterial vessels, were evaluated retrospectively in order to assess the role of regional anesthesia in this group. In 33.8% regional anethesia with or without some form of suppletion was considered to be the anesthetic of choice. Regional anesthesia is especially indicated in those patients admitted for intractable ischaemic pain. As an anesthetic for the surgical procedure, it should be considered as a choice possibility as good as general anesthesia and in some cases as a better one.