Renal function and natriuresis-guided diuretic therapy - a pre-specified analysis from the PUSH-AHF trial.

AIM: In a randomized controlled trial, we recently showed that a natriuresis-guided diuretic approach improved natriuresis and diuresis in patients with acute heart failure (HF). In this pre-specified analysis, we investigated the association between (worsening) renal function, outcomes and the effect of intensive natriuresis-guided loop diuretic therapy as compared with standard of care. METHODS AND RESULTS: The Pragmatic Urinary Sodium-based algoritHm in Acute Heart Failure (PUSH-AHF) trial randomized patients to natriuresis-guided diuretic therapy or standard of care. Serum creatinine and estimated glomerular filtration rate (eGFR) were assessed at fixed timepoints, and worsening renal function (WRF) was assessed at 72 h. The primary outcome was the interaction between randomized treatment allocation, baseline eGFR and the dual primary outcome of PUSH-AHF: total natriuresis at 24 h and time to all-cause mortality or HF rehospitalization at 180 days. In 309 patients, median baseline eGFR was 53 (35-73) ml/min/1.73 m2, and 58% had eGFR <60 ml/min/1.73 m2. Baseline eGFR did not significantly modify the treatment effect of natriuresis-guided diuretic therapy on natriuresis at 24 h (p for interaction = 0.730). However, baseline eGFR significantly modified the effect on all-cause mortality and HF rehospitalization (p for interaction = 0.017): the risk of this second primary outcome was lower in patients with lower eGFR who were randomized to the natriuresis-guided group. In the natriuresis-guided arm, eGFR decreased more (-11.0 vs. -6.91 ml/min/1.73 m2; p = 0.002) during the first 3 days, but this effect was attenuated at discharge (-10.3 vs. -8.69 ml/min/1.73 m2; p = 0.38). WRF was more frequently observed in patients randomized to natriuresis-guided treatment, but was not associated with worse clinical outcomes. CONCLUSIONS: Natriuresis-guided diuretic treatment improved diuresis and natriuresis irrespective of baseline eGFR and occurrence of WRF, was effective even in patients with low eGFR, and the observed effect on eGFR was transient and not associated with worse clinical outcomes.

Natriuresis-guided diuretic therapy in acute heart failure: a pragmatic randomized trial.

Measurement of natriuresis has been suggested as a reliable, easily obtainable biomarker for assessment of the response to diuretic treatment in patients with acute heart failure (AHF). Here, to assess whether natriuresis-guided diuretic therapy in patients with AHF improves natriuresis and clinical outcomes, we conducted the pragmatic, open-label Pragmatic Urinary Sodium-based algoritHm in Acute Heart Failure trial, in which 310 patients (45% female) with AHF requiring treatment with intravenous loop diuretics were randomly assigned to natriuresis-guided therapy or standard of care (SOC). In the natriuresis-guided arm, natriuresis was determined at set timepoints, prompting treatment intensification if spot urinary sodium levels were <70 mmol l-1. The dual primary endpoints were 24 h urinary sodium excretion and a combined endpoint of time to all-cause mortality or adjudicated heart failure rehospitalization at 180 days. The first primary endpoint was met, as natriuresis in the natriuresis-guided and SOC arms was 409 ± 178 mmol arm versus 345 ± 202 mmol, respectively (P = 0.0061). However, there were no significant differences between the two arms for the combined endpoint of time to all-cause mortality or first heart failure rehospitalization, which occurred in 46 (31%) and 50 (31%) of patients in the natriuresis-guided and SOC arms, respectively (hazard ratio 0.92 [95% confidence interval 0.62-1.38], P = 0.6980). These findings suggest that natriuresis-guided therapy could be a first step towards personalized treatment of AHF. ClinicalTrials.gov registration: NCT04606927 .

Natriuresis-guided therapy in acute heart failure: rationale and design of the Pragmatic Urinary Sodium-based treatment algoritHm in Acute Heart Failure (PUSH-AHF) trial.

AIMS: Insufficient diuretic response frequently occurs in patients admitted for acute heart failure (HF) and is associated with worse clinical outcomes. Recent studies have shown that measuring natriuresis early after hospital admission could reliably identify patients with a poor diuretic response during hospitalization who might require enhanced diuretic treatment. This study will test the hypothesis that natriuresis-guided therapy in patients with acute HF improves natriuresis and clinical outcomes. METHODS: The Pragmatic Urinary Sodium-based treatment algoritHm in Acute Heart Failure (PUSH-AHF) is a pragmatic, single-centre, randomized, controlled, open-label study, aiming to recruit 310 acute HF patients requiring treatment with intravenous loop diuretics. Patients will be randomized to natriuresis-guided therapy or standard of care. Natriuresis will be determined at set time points after initiation of intravenous loop diuretics, and treatment will be adjusted based on the urinary sodium levels in the natriuresis-guided group using a pre-specified stepwise approach of increasing doses of loop diuretics and the initiation of combination diuretic therapy. The co-primary endpoint is 24-h urinary sodium excretion after start of loop diuretic therapy and a combined endpoint of all-cause mortality or first HF rehospitalization at 6 months. Secondary endpoints include 48- and 72-h sodium excretion, length of hospital stay, and percentage change in N-terminal pro brain natriuretic peptide at 48 and 72 h. CONCLUSION: The PUSH-AHF study will investigate whether natriuresis-guided therapy, using a pre-specified stepwise diuretic treatment approach, improves natriuresis and clinical outcomes in patients with acute HF.

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.

Clinical importance of urinary sodium excretion in acute heart failure.

AIMS: Urinary sodium assessment has recently been proposed as a target for loop diuretic therapy in acute heart failure (AHF). We aimed to investigate the time course, clinical correlates and prognostic importance of urinary sodium excretion in AHF. METHODS AND RESULTS: In a prospective cohort of 175 consecutive patients with an admission for AHF we evaluated urinary sodium excretion 6 h after initiation of loop diuretic therapy. Clinical outcome was all-cause mortality or heart failure rehospitalization. Mean age was 71 ± 14 years, and 44% were female. Median urinary sodium excretion was 130 (67-229) mmol at 6 h, 347 (211-526) mmol at 24 h, and decreased from day 2 to day 4. Lower urinary sodium excretion was independently associated with male gender, younger age, renal dysfunction and pre-admission loop diuretic use. There was a strong association between urinary sodium excretion at 6 h and 24 h urine volume (beta = 0.702, P < 0.001). Urinary sodium excretion after 6 h was a strong predictor of all-cause mortality after a median follow-up of 257 days (hazard ratio 3.81, 95% confidence interval 1.92-7.57; P < 0.001 for the lowest vs. the highest tertile of urinary sodium excretion) independent of established risk factors and urinary volume. Urinary sodium excretion was not associated with heart failure rehospitalization. CONCLUSION: In a modern, unselected, contemporary AHF population, low urinary sodium excretion during the first 6 h after initiation of loop diuretic therapy is associated with lower urine output in the first day and independently associated with all-cause mortality.

Investigating possible causes of bias in a progress test translation: an one-edged sword.

PURPOSE: Assessment in different languages should measure the same construct. However, item characteristics, such as item flaws and content, may favor one test-taker group over another. This is known as item bias. Although some studies have focused on item bias, little is known about item bias and its association with items characteristics. Therefore, this study investigated the association between item characteristics and bias. METHODS: The University of Groningen offers both an international and a national bachelor's program in medicine. Students in both programs take the same progress test, but the international progress test is literally translated into English from the Dutch version. Differential item functioning was calculated to analyze item bias in four subsequent progress tests. Items were also classified by their categories, number of alternatives, item flaw, item length, and whether it was a case-based question. RESULTS: The proportion of items with bias ranged from 34% to 36% for the various tests. The number of items and the size of their bias was very similar in both programmes. We have identified that the more complex items with more alternatives favored the national students, whereas shorter items and fewer alternatives favored the international students. CONCLUSION: Although nearly 35% of all items contain bias, the distribution and the size of the bias were similar for both groups. The findings of this paper may be used to improve the writing process of the items, by avoiding some characteristics that may benefit one group whilst being a disadvantage for others.

Long-term outcome of elderly out-of-hospital cardiac arrest survivors as compared with their younger counterparts and the general population.

BACKGROUND:: Over the past decade, prehospital and in-hospital treatment for out-of-hospital cardiac arrest (OHCA) has improved considerably. There are sparse data on the long-term outcome, especially in elderly patients. We studied whether elderly patients benefit to the same extent compared with younger patients and at long-term follow up as compared with the general population. METHODS:: Between 2001 and 2010, data from all patients presented to our hospital after OHCA were recorded. Elderly patients (⩾75 years) were compared with younger patients. Neurological outcome was classified as cerebral performance category (CPC) at hospital discharge and long-term survival was compared with younger patients and predicted survival rates of the general population. RESULTS:: Of the 810 patients admitted after OHCA, a total of 551 patients (68%) achieved return of spontaneous circulation, including 125 (23%) elderly patients with a mean age of 81 ± 5 years. In-hospital survival was lower in elderly patients compared with younger patients with rates of 33% versus 57% ( p < 0.001). A CPC of 1 was present in 73% of the elderly patients versus 86% of the younger patients ( p = 0.031). In 7.3% of the elderly patients, a CPC >2 was observed versus 2.5% of their younger counterparts ( p = 0.103). Elderly patients had a median survival of 6.5 [95% confidence interval (CI) 2.0-7.9] years compared with 7.7 (95% CI 7.5-7.9) years of the general population ( p = 0.019). CONCLUSIONS:: The survival rate after OHCA in elderly patients is approximately half that of younger patients. Elderly patients who survive to discharge frequently have favorable neurological outcomes and a long-term survival that approximates that of the general population.

The electrocardiographic manifestations of athlete's heart and their association with exercise exposure.

OBJECTIVE: The aim of this study was to define the minimum amount of exercise per week ('current exposure') and the total amount of exercise ('lifetime exposure') needed to lead to the electrocardiographic changes fitting athlete's heart. METHODS: All the pre-participation screenings (including electrocardiograms (ECGs)) from collegiate athletes performed at University Sports Medical Center in 2013 and 2014 were collected. Data on height, weight, sex, age, current sport(s) participation and lifetime sport(s) participation were collected. Current exposure was categorised into 0-3, 3-6, 6-10 and >10 hours/week. Lifetime sport exposure was divided into five categories: 0-1000, 1001-2000, 2001-3000, 3001-4000 and >4000 hours. RESULTS: The study population consisted of 1229 athletes (current exposure) and 1104 athletes (lifetime exposure). Current sport exposure: There was a significant increase in training-related ECG changes in the category 3-6 vs. <3 hours/week. When looking at individual parameters, we found an association with a significant difference in sinus bradycardia and QRS voltage (<3 vs. 3-6 hours/week) and first-degree AV-block (<3 vs. >10 hours/week).Lifetime sport exposure: There was an increase in training-related ECG changes that reached significance at an exposure >3000 hours. When looking at individual parameters, we found an association with a significant difference in sinus bradycardia (0-1000 vs. 2001-3000), QRS voltage (0-1000 vs. 3001-4000) and first-degree AV-block (0-1000 vs. >4000). CONCLUSION: A minimum of ≥3 hours/week of current exposure and a lifetime exposure of >3000 hours is needed to lead to the electrocardiographic changes fitting athlete's heart.

Orthostatic blood pressure recovery patterns in suspected syncope in the emergency department.

INTRODUCTION: Orthostasis is a frequent trigger for (pre)syncope but some forms of orthostatic (pre)syncope have a worse prognosis than others. Routine assessment of orthostatic BP in the ED can detect classic orthostatic hypotension, but often misses these other forms of orthostatic (pre)syncope. This study aimed to determine the frequency of abnormal orthostatic BP recovery patterns in patients with (pre)syncope by using continuous non-invasive BP monitoring. METHODS: We performed a prospective cohort study in suspected patients with (pre)syncope in the ED of a tertiary care teaching hospital between January and August 2014. Orthostatic BP was measured during the active lying-to-standing test with Nexfin, a continuous non-invasive finger arterial pressure measurement device. Orthostatic BP recovery patterns were defined as normal BP recovery, initial orthostatic hypotension, delayed BP recovery, classic orthostatic hypotension and reflex-mediated hypotension. RESULTS: Of 116 patients recruited, measurements in 111 patients (age 63 years, 51% male) were suitable for analysis. Classic orthostatic hypotension was the most prevalent abnormal BP pattern (19%), but only half of the patients received a final diagnosis of orthostatic hypotension. Initial orthostatic hypotension and delayed BP recovery were present in 20% of the patients with (pre)syncope of whom 45% were diagnosed as unexplained syncope. Reflex-mediated hypotension was present in 4% of the patients. CONCLUSION: Continuous non-invasive BP measurement can potentially identify more specific and concerning causes of orthostatic (pre)syncope. Correct classification is important because of different short-term and long-term clinical implications.

Gender differences in the electrocardiogram screening of athletes.

OBJECTIVES: Gender-related differences are frequently used in medicine. Electrocardiograms are also subject to such differences. This study evaluated gender differences in ECG parameters of young athletes, discussing the possible implications of these differences for ECG criteria used in the cardiovascular screening of young athletes. DESIGN: Observational cross-sectional study. METHODS: In 2013 and 2014 all the ECGs from the cardiovascular screenings performed at University Sports Medical Centre in Groningen of the student athletes who wanted to participate in a college sports program were collected. The ECG characteristics were scored using computer-based measurements and the Seattle ECG criteria. RESULTS: The study population included 1436 athletes, of which 72% were male. Male athletes were older (19.3 years vs. 18.6 years), participated in sports more frequently (4.0/week vs. 3.8/week) and spent more hours per week practising sports (6.4h/week vs. 5.8h/week) than female athletes. Male athletes had significantly higher PR intervals (149ms vs. 141ms), lead voltages and QRS duration (98ms vs. 88ms). Female athletes had significantly higher resting heart rates (69/min vs. 64/min) and QTc intervals (407ms vs. 400ms). Male athletes also had significantly higher amounts of sinus bradycardia (38.3% vs. 23.0%), incomplete RBBB (15.0% vs. 3.7%), early repolarisation (4.5% vs. 1.0%) and isolated QRS voltage criteria for LVH (26.3% vs. 4.6%). All P-values were ≤0.001. CONCLUSIONS: ECGs of young athletes demonstrate gender-related differences. These differences could be considered in their cardiovascular screening. For the Seattle ECG criteria we advise additional research into the clinical implications of using gender-based cut-off values for the QRS duration in the intraventricular conduction delay criterion.

HDL function is impaired in acute myocardial infarction independent of plasma HDL cholesterol levels.

BACKGROUND: High-density lipoproteins (HDLs) protect against the development of atherosclerotic cardiovascular disease. HDL function represents an emerging concept in cardiovascular research. OBJECTIVE: This study investigated the association between HDL functionality and acute myocardial infarction (MI) independent of HDL-cholesterol plasma levels. METHODS: Participants (non-ST-segment elevation MI, non-STEMI, n = 41; STEMI, n = 37; non-MI patients, n = 33) from a prospective follow-up study enrolling patients with acute chest pain were matched for age and plasma HDL cholesterol. The in vitro capacity of HDL to (1) mediate cholesterol efflux from macrophage foam cells, (2) prevent low-density lipoprotein oxidation, and (3) inhibit TNF-α-induced vascular adhesion molecule-1 expression in endothelial cells was determined. RESULTS: STEMI-HDL displayed reduced cholesterol efflux (P < .001) and anti-inflammatory functionality (P = .001), whereas the antioxidative properties were unaltered. Cholesterol efflux correlated with the anti-inflammatory HDL activity (P < .001). Not C-reactive protein levels, a marker of systemic inflammation, but specifically plasma myeloperoxidase levels were independently associated with impaired HDL function (efflux: P = .022; anti-inflammation: P < .001). Subjects in the higher risk quartile of efflux (odds ratio [OR], 5.66; 95% confidence interval [CI], 1.26-25.00; P = .024) as well as anti-inflammatory functionality of HDL (OR, 5.53; 95% CI, 1.83-16.73; P = .002) had a higher OR for MI vs those in the three lower risk quartiles combined. CONCLUSION: Independent of plasma HDL cholesterol levels, 2 of 3 antiatherogenic HDL functionalities tested were significantly impaired in STEMI patients, namely cholesterol efflux and anti-inflammatory properties. Increased myeloperoxidase levels might represent a major contributing mechanism for decreased HDL functionality in MI patients.

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.

Effect of metformin on left ventricular function after acute myocardial infarction in patients without diabetes: the GIPS-III randomized clinical trial.

IMPORTANCE: Metformin treatment is associated with improved outcome after myocardial infarction in patients with diabetes. In animal experimental studies metformin preserves left ventricular function. OBJECTIVE: To evaluate the effect of metformin treatment on preservation of left ventricular function in patients without diabetes presenting with ST-segment elevation myocardial infarction (STEMI). DESIGN, SETTING, AND PARTICIPANTS: Double-blind, placebo-controlled study conducted among 380 patients who underwent primary percutaneous coronary intervention (PCI) for STEMI at the University Medical Center Groningen, The Netherlands, between January 1, 2011, and May 26, 2013. INTERVENTIONS: Metformin hydrochloride (500 mg) (n = 191) or placebo (n = 189) twice daily for 4 months. MAIN OUTCOMES AND MEASURES: The primary efficacy measure was left ventricular ejection fraction (LVEF) after 4 months, assessed by magnetic resonance imaging. A secondary efficacy measure was the N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration after 4 months. The incidence of major adverse cardiac events (MACE; the combined end point of death, reinfarction, or target-lesion revascularization) was recorded until 4 months as a secondary efficacy measure. RESULTS: At 4 months, all patients were alive and none were lost to follow-up. LVEF was 53.1% (95% CI, 51.6%-54.6%) in the metformin group (n = 135), compared with 54.8% (95% CI, 53.5%-56.1%) (P = .10) in the placebo group (n = 136). NT-proBNP concentration was 167 ng/L in the metformin group (interquartile range [IQR], 65-393 ng/L) and 167 ng/L in the placebo group (IQR, 74-383 ng/L) (P = .66). MACE were observed in 6 patients (3.1%) in the metformin group and in 2 patients (1.1%) in the placebo group (P = .16). Creatinine concentration (79 µmol/L [IQR, 70-87 µmol/L] vs 79 µmol/L [IQR, 72-89 µmol/L], P = .61) and glycated hemoglobin (5.9% [IQR, 5.6%-6.1%] vs 5.9% [IQR, 5.7%-6.1%], P = .15) were not significantly different between both groups. No cases of lactic acidosis were observed. CONCLUSIONS AND RELEVANCE: Among patients without diabetes presenting with STEMI and undergoing primary PCI, the use of metformin compared with placebo did not result in improved LVEF after 4 months. The present findings do not support the use of metformin in this setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01217307.

Are grown-ups with congenital heart disease willing to participate in an exercise program?

OBJECTIVE: To examine the willingness of grown-ups with congenital heart disease (GUCH) to participate in the GUCH Training Program-Individualised (GTI), an exercise program specifically designed for GUCH, and to identify factors affecting their willingness to participate. DESIGN AND SETTING: In this cross-sectional study, all outpatient GUCH of the University Medical Center Groningen in The Netherlands, living within a 30-km radius of Groningen (n = 311), were asked to participate. PATIENTS: In total, 116 (37%) of the 311 GUCH who are invited to participate in our study returned completed questionnaires. The median age of the respondents was 40 (interquartile range 31-50) years and 55% were women. OUTCOME MEASURES: Respondents (n = 116) completed a questionnaire that queried physical activity, perceived physical fitness, psychosocial determinants (motivation, self-efficacy, and social support) related to physical activity, and willingness to participate in GTI. RESULTS: Of the 116 respondents, 68 (59%) were willing to participate in GTI. They were less physically active, had worse perceived physical fitness, were less satisfied with their fitness, were generally more motivated to engage in physical activity, and had more social support than patients unwilling to participate. The best logistic regression model predicting willingness to participate in GTI included the variables perceived physical fitness and motivation for physical activity in general. CONCLUSIONS: Asking GUCH to participate in an exercise program supervised by physical therapists is a good strategy. Taken into account nonresponse, a participation rate in the exercise program of over 20% is to be expected. Perceived physical fitness and motivation for physical activity in general are important predictors of patients' willingness to participate.

Interhospital transfer due to failed prehospital diagnosis for primary percutaneous coronary intervention: an observational study on incidence, predictors, and clinical impact.

BACKGROUND: For patients with ST-elevation myocardial infarction (STEMI), guidelines recommend prehospital triage and direct referral to a percutaneous coronary intervention (PCI)-capable centre in order to minimize ischemic time. However, few have studied failed prehospital diagnosis. We assessed the incidence, predictors, and clinical impact of interhospital transfer for primary PCI after initial referral to a non-PCI-capable centre due to a failed prehospital STEMI diagnosis. METHODS: We studied 846 consecutive STEMI patients undergoing primary PCI between January 2008 and January 2010. RESULTS: We found that 609 patients (72%) were directly admitted through prehospital triage and 127 patients (15%) required interhospital transfer after failed prehospital diagnosis. Median first medical contact to treatment time was 88 min in the prehospital diagnosis group and 155 min in the interhospital transfer group (p<0.001). In the interhospital transfer group, the first available electrocardiogram was diagnostic for STEMI in 77% of cases. Predictors of interhospital transfer were female gender, diabetes, prior myocardial infarction, and greater event location to PCI-capable centre distance. Interhospital transfer independently accounted for a 47% increase in ischemic time (95% CI 33 to 63%; p<0.001). One-year mortality was higher in the interhospital transfer group (10 vs. 5.3%; p=0.030). CONCLUSIONS: Despite an often-diagnostic electrocardiogram, interhospital transfer after failed prehospital diagnosis occurred in 15% of STEMI patients undergoing primary PCI. Interhospital transfer was a major predictor of ischemic time and 1-year mortality was significantly higher. Continuing efforts to optimize prehospital triage are warranted, especially among patients at higher risk of failed prehospital diagnosis.

Quick identification of acute chest pain patients study (QICS).

BACKGROUND: Patients with acute chest pain are often referred to the emergency ward and extensively investigated. Investigations are costly and could induce unnecessary complications, especially with invasive diagnostics. Nevertheless, chest pain patients have high mortalities. Fast identification of high-risk patients is crucial. Therefore several strategies have been developed including specific symptoms, signs, laboratory measurements, and imaging. METHODS/DESIGN: The Quick Identification of acute Chest pain Study (QICS) will investigate whether a combined use of specific symptoms and signs, electrocardiography, routine and new laboratory measures, adjunctive imaging including electron beam (EBT) computed tomography (CT) and contrast multislice CT (MSCT) will have a high diagnostic yield for patients with acute chest pain. All patients will be investigated according a standardized protocol in the Emergency Department. Serum and plasma will be frozen for future analysis for a wide range of biomarkers at a later time point. The primary endpoint is the safe recognition of low-risk chest pain patients directly at presentation. Secondary endpoint is the identification of a wide range of sensitive predictive clinical markers, chemical biomarkers and radiological markers in acute chest pain patients. Chemical biomarkers will be compared to quantitative CT measurements of coronary atherosclerosis as a surrogate endpoint. Chemical biomarkers will also be compared in head to head comparison and for their additional value. DISCUSSION: This will be a very extensive investigation of a wide range of risk predictors in acute chest pain patients. New reliable fast and cheap diagnostic algorithm resulting from the test results might improve chest pain patients' prognosis, and reduce unnecessary costs and diagnostic complications.

The value and limitations of a wound inspection clinic after cardiac device implantation.

BACKGROUND: Due to the growing number of cardiac device implantations it is important to develop methods to reduce device-implantation related complications. AIMS: To determine whether a wound inspection clinic can play a role in the detection of device-implantation related complications. METHODS: Single-center observational study evaluating patients who received a pacemaker or implantable cardioverter-defibrillator (ICD). RESULTS: Of 159 patients who received an appointment for the wound inspection clinic, 52 (33%) received a pacemaker and 107 (67%) received an ICD. The majority had no signs of infection. Pain (n = 13,8%) and swelling (n = 11,7%) were the most frequent signs observed, but they never necessitated intervention and recovered spontaneously in all patients. During follow-up (mean 20+/-9 weeks), complications occurred in 10 patients (6%). Most complications occurred early, within 4 days after implantation. The two late complications (at 19 and 41 days) could not be recognized at the wound inspection clinic. CONCLUSION: We found no useful role for a wound inspection clinic two weeks post-implant to detect device-related complications. Open rapid access to the pacemaker/ICD center for patients with signs and symptoms of (threatening) complications seems to be more appropriate to manage post-implant patients.

Importance of heart rate during exercise for response to cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) is an established therapy for patients with severe heart failure and mechanical dyssynchrony. Response is only achieved in 60-70% of patients. OBJECTIVES: To study exercise-related factors predicting response to CRT. METHODS: We retrospectively examined consecutive patients in whom a CRT device was implanted. All underwent cardiopulmonary exercise testing prior to implantation and after 6 months. The occurrence of chronotropic incompetence and heart rates exceeding the upper rate of the device, thereby compromising biventricular stimulation, was studied. Response was defined as a decrease in LVESV of 10% or more after 6 months. RESULTS: We included 144 patients. After 6 months 86 (60%) patients were responders. Peak VO2 significantly increased in responders. Chronotropic incompetence was more frequently seen in nonresponders (21 [36%] vs 9 [10%], P = 0.03), mostly in patients in SR. At moderate exercise, defined as 25% of the maximal exercise tolerance, that is, comparable to daily life exercise, nonresponders more frequently went above the upper rate of the device (13 [22%] vs 2 [3%], P < 0.0001), most of whom were patients in permanent AF. Multivariate analysis revealed heart rates not exceeding the upper rate of the device during moderate exercise (OR 15.8 [3.3-76.5], P = 0.001) and nonischemic cardiomyopathy (OR 2.4 [1.0-5.7], P = 0.04) as predictive for response. CONCLUSIONS: Heart rate exceeding the upper rate during moderate exercise is an independent predictor for nonresponse to CRT in patients with AF, whereas chronotropic incompetence is a predictor for patients in SR.

Impact of interventricular lead distance and the decrease in septal-to-lateral delay on response to cardiac resynchronization therapy.

AIMS: To investigate the influence of interlead distance and lead positioning on success of cardiac resynchronization therapy (CRT) in patients with advanced chronic heart failure and electrical dyssynchrony. Despite application of established selection criteria, 20-40% of the patients do not respond to CRT. METHODS AND RESULTS: We examined consecutive patients in whom CRT was implanted. Response to CRT was defined as a decrease in the left ventricular end-systolic volume >or=10% after 6 months. A comparison was made between patients who were responders to CRT and those who were non-responders. A univariate and stepwise multivariate logistic regression was performed with regard to predictors for response. Between January 2004 and January 2008, 174 patients who were treated with CRT were classified as responders [n = 95 (55%)] or non-responders [n = 79 (45%)]. Responders had a significantly larger horizontal interlead distance on the lateral thoracic X-ray [odds ratio (OR) 2.8 (1.2-6.6), P = 0.01], a septal-to-lateral delay >60 ms [OR 4.9 (2.0-11.4), P < 0.0001], non-ischaemic cardiomyopathy [OR 3.0 (1.3-6.9), P = 0.009], a left ventricular end-diastolic diameter <67 mm [OR 4.2 (1.8-9.9), P = 0.001], angiotensin-converting enzyme inhibitor use [OR 8.1 (1.7-38.2), P = 0.008], and no tricuspid valve insufficiency [OR 6.9 (1.3-35.5), P = 0.02]. Post-implantation responders had a significantly greater decrease in the intraventricular delay (septal-to-lateral delay 62 +/- 62 vs. 26 +/- 65 ms, P = 0.001), but not in the interventricular mechanical delay. CONCLUSION: Larger interlead distance on the lateral thoracic X-ray, associated with positioning of the left ventricular lead in the posterior position, is associated with response after 6 months of follow-up. Furthermore, diminishing the septal-to-lateral delay is predictive for response.

Cardiac resynchronization therapy in patients with heart failure and atrial fibrillation: importance of new-onset atrial fibrillation and total atrial conduction time.

AIMS: Cardiac resynchronization therapy (CRT) is an established therapy for patients with heart failure and sinus rhythm (SR), but its value in atrial fibrillation (AF) remains unclear. Furthermore, response to CRT may be difficult to predict in these patients. The aim of our study was to investigate whether predictors for CRT success differ between patients with AF and SR and to study the influence of present or developing AF on response to CRT. METHODS AND RESULTS: We examined consecutive patients in whom CRT was implanted disregarding the atrial rhythm. Atrial fibrillation was defined as either current or earlier AF, response to CRT was defined as a decrease in the left ventricular end-systolic volume of > or = 10% after 6 months. Total atrial conduction time (TACT), a measure to predict the risk of developing AF, was determined by echocardiography. We included 114 patients, of whom 56 (49%) were known with AF (23 current AF and 33 earlier AF). The other 58 patients had no history of AF. After 6 months, response in current and earlier AF and that in SR patients was comparable (56, 58 and 55%, respectively). In AF patients, multivariate analysis revealed a shorter TACT at baseline [odds ratio (OR) 16.7 (1.5-185.3), P = 0.02] and an interventricular mechanical delay (IVMD) > 40 ms [OR 10.4 (1.0-110.9), P = 0.05] as predictors for response. Non-responders more frequently suffered from new-onset AF (P = 0.02). CONCLUSION: Failure to CRT is associated with new-onset AF. Total atrial activation time may be a parameter to predict response in AF patients.