Pragmatic randomized controlled trials: strengthening the concept through a robust international collaborative network: PRIME-9-Pragmatic Research and Innovation through Multinational Experimentation.

In an era focused on value-based healthcare, the quality of healthcare and resource allocation should be underpinned by empirical evidence. Pragmatic clinical trials (pRCTs) are essential in this endeavor, providing randomized controlled trial (RCT) insights that encapsulate real-world effects of interventions. The rising popularity of pRCTs can be attributed to their ability to mirror real-world practices, accommodate larger sample sizes, and provide cost advantages over traditional RCTs. By harmonizing efficacy with effectiveness, pRCTs assist decision-makers in prioritizing interventions that have a substantial public health impact and align with the tenets of value-based health care. An international network for pRCT provides several advantages, including larger and diverse patient populations, access to a broader range of healthcare settings, sharing knowledge and expertise, and overcoming ethical and regulatory barriers. The hypothesis and study design of pRCT answers the decision-maker's questions. pRCT compares clinically relevant alternative interventions, recruits participants from diverse practice settings, and collects data on various health outcomes. They are scarce because the medical products industry typically does not fund pRCT. Prioritizing these studies by expanding the infrastructure to conduct clinical research within the healthcare delivery system and increasing public and private funding for these studies will be necessary to facilitate pRCTs. These changes require more clinical and health policy decision-makers in clinical research priority setting, infrastructure development, and funding. This paper presents a comprehensive overview of pRCTs, emphasizing their importance in evidence-based medicine and the advantages of an international collaborative network for their execution. It details the development of PRIME-9, an international initiative across nine countries to advance pRCTs, and explores various statistical approaches for these trials. The paper underscores the need to overcome current challenges, such as funding limitations and infrastructural constraints, to leverage the full potential of pRCTs in optimizing healthcare quality and resource utilization.

Prehospital risk stratification in patients with chest pain.

OBJECTIVES: The History, ECG, Age, Risk Factors and Troponin (HEART) Score is a decision support tool applied by physicians in the emergency department developed to risk stratify low-risk patients presenting with chest pain. We assessed the potential value of this tool in prehospital setting, when applied by emergency medical services (EMS), and derived and validated a tool adapted to the prehospital setting in order to determine if it could assist with decisions regarding conveyance to a hospital. METHODS: In 2017, EMS personnel prospectively determined the HEART Score, including point-of-care (POC) troponin measurements, in patients presenting with chest pain, in the north of the Netherlands. The primary endpoint was a major adverse cardiac event (MACE), consisting of acute myocardial infarction or death, within 3 days. The components of the HEART Score were evaluated for their discriminatory value, cut-offs were calibrated for the prehospital setting and sex was substituted for cardiac risk factors to develop a prehospital HEART (preHEART) Score. This score was validated in an independent prospective cohort of 435 patients in 2018. RESULTS: Among 1208 patients prospectively recruited in the first cohort, 123 patients (10.2%) developed a MACE. The HEART Score had a negative predictive value (NPV) of 98.4% (96.4-99.3), a positive predictive value (PPV) of 35.5% (31.8-39.3) and an area under the receiver operating characteristic curve (AUC) of 0.81 (0.78-0.85). The preHEART Score had an NPV of 99.3% (98.1-99.8), a PPV of 49.4% (42.0-56.9) and an AUC of 0.85 (0.82-0.88), outperforming the HEART Score or POC troponin measurements on their own. Similar results were found in a validation cohort. CONCLUSIONS: The HEART Score can be used in the prehospital setting to assist with conveyance decisions and choice of hospitals; however, the preHEART Score outperforms both the HEART Score and single POC troponin measurements when applied by EMS personnel in the prehospital setting.

Defining and Measuring a Standard Set of Patient-Relevant Outcomes in Coronary Artery Disease.

Systematic outcome measurement enables to continuously improve treatment results and stimulates dissemination of best practices. For patients with coronary artery disease, no examples yet exist of standard sets of patient-relevant outcome measures that have already been fully implemented at a large scale in clinical care. The aim of this paper is twofold: (1) to share the standard set of outcome measures as developed by Meetbaar Beter, and (2) to show how the standard set is presented and published to support improvement of cardiac care. A step-wise approach was followed by an expert panel to construct a standard set of outcome measures. This resulted in a comprehensive set of relevant outcome measures, comprising 4 generic and 11 treatment-specific outcomes. Both short-term and long-term outcomes measures up to 5 years of follow-up were included. Relevant initial conditions were selected to enable case-mix adjustment. The standard set has been implemented in 21 hospitals across the Netherlands. The results and experiences have been used to fine-tune the set in 4 reporting cycles in 2012 to 2016, using an annual maintenance cycle. Currently about 83,000 percutaneous coronary interventions and 30,000 coronary artery bypass graftings are included in the dataset, covering the majority of all percutaneous coronary interventions and coronary artery bypass graftings in the Netherlands. In conclusion, Meetbaar Beter has defined and implemented a comprehensive set of patient-relevant outcome measures for coronary artery disease, and the variation of the results among the centers indicates that there are sufficient opportunities to further improve cardiac care in the Netherlands.

Long-term outcome of patients after out-of-hospital cardiac arrest in relation to treatment: a single-centre study.

INTRODUCTION: Outcome after out-of-hospital cardiac arrest (OHCA) remains poor. With the introduction of automated external defibrillators, percutaneous coronary intervention (PCI) and mild therapeutic hypothermia (MTH) the prognosis of patients after OHCA appears to be improving. The aim of this study was to evaluate short and long-term outcome among a non-selected population of patients who experienced OHCA and were admitted to a hospital working within a ST elevation myocardial infarction network. METHODS: All patients who achieved return of spontaneous circulation (ROSC) (n=456) admitted to one hospital after OHCA were included. Initial rhythm, reperfusion therapy with PCI, implementation of MTH and additional medical management were recorded. The primary outcome measure was survival (hospital and long term). Neurological status was measured as cerebral performance category. The inclusion period was January 2003 to August 2010. Follow-up was complete until April 2014. RESULTS: The mean patient age was 63±14 years and 327 (72%) were men. The initial rhythm was ventricular fibrillation, pulseless electrical activity, asystole and pulseless ventricular tachycardia in 322 (71%), 58 (13%), 55 (12%) and 21 (5%) of the 456 patients, respectively. Treatment included PCI in 191 (42%) and MTH in 188 (41%). Overall in-hospital and long-term (5-year) survival was 53% (n=240) and 44% (n=202), respectively. In the 170 patients treated with primary PCI, in-hospital survival was 112/170 (66%). After hospital discharge these patients had a 5-year survival rate of 99% and cerebral performance category was good in 92%. CONCLUSIONS: In this integrated ST elevation myocardial infarction network survival and neurological outcome of selected patients with ROSC after OHCA and treated with PCI was good. There is insufficient evidence about the outcome of this approach, which has a significant impact on utilisation of resources. Good quality randomised controlled trials are needed. In selected patients successfully resuscitated after OHCA of presumed cardiac aetiology, we believe that a more liberal application of primary PCI may be considered in experienced acute cardiac referral centres.

Heart failure highlights in 2012-2013.

Heart failure has become the cardiovascular epidemic of the century. The European Journal of Heart Failure is dedicated to the advancement of knowledge in the field of heart failure management. In 2012 and 2013, several pioneering scientific discoveries and paradigm-shifting clinical trials have been published. In the current paper, we will discuss the most significant novel insights into the pathophysiology, diagnosis, and treatment of heart failure that were published during this period. All relevant research areas are discussed, including pathophysiology, co-morbidities, arrhythmias, biomarkers, clinical trials, and device therapy, including left ventricular assist devices.

Galectin-3 is an independent marker for ventricular remodeling and mortality in patients with chronic heart failure.

BACKGROUND: Galectin-3 (Gal-3) is a recently discovered marker for myocardial fibrosis and elevated levels are associated with an impaired outcome after short-term follow-up in heart failure (HF) patients. However, whether Gal-3 is related to cardiac remodeling and outcome after long-term follow-up is unknown. Therefore, we determined the utility of Gal-3 as a novel biomarker for left ventricular remodeling and long-term outcome in patients with severe chronic HF. METHODS AND RESULTS: A total of 240 HF patients with New York Heart Association (NYHA) Class III and IV were included. Patients were followed for 8.7 ± 1 years, had a mean age of 71 ± 0.6 years and 73 % of the study population was male. Circulating levels of NT-proBNP and Gal-3 were measured. Serial echocardiography was performed at baseline and at 3 months. At baseline median left ventricular end-diastolic volume (LVEDV) was 267 mL [interquartile range 232-322]. Patients were divided into three groups according to the change in LVEDV. Patients in whom the LVEDV decreased over time had significant lower levels of Gal-3 at entry compared to patients in whom the LVEDV was stable or increased (14.7 vs. 17.9 vs. 19.0 ng/mL; p = 0.004 for trend), whereas no significant differences were seen in levels of NT-proBNP (p = 0.33). Multivariate linear regression analyses revealed that Gal-3 levels were positively correlated to change in LVEDV (p = 0.007). In addition, Gal-3 was a significant predictor of mortality after long-term follow-up (p = 0.001). CONCLUSION: Gal-3 is associated with left ventricular remodeling determined by serial echocardiography and predicts long-term mortality in patients with severe chronic HF.