Wybe Nieuwland

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.

Differential effects of high-frequency versus low-frequency exercise training in rehabilitation of patients with coronary artery disease

OBJECTIVES We sought to study the influence of frequency of exercise training during cardiac rehabilitation on functional capacity (i.e., peak oxygen consumption [VO2] and ventilatory anaerobic threshold [VAT]) and quality of life (QoL). BACKGROUND Although the value of cardiac rehabilitation is now well established, the influence of the different program characteristics on outcome has received little attention, and the effect of frequency of exercise training is unclear. Functional capacity is regularly evaluated by peak VO2 but parameters of submaximal exercise capacity such as VAT should also be considered because submaximal exercise capacity is especially important in daily living. METHODS Patients with coronary artery disease (n = 130, 114 men; mean age 52 +/- 9 years) were randomized to either a high- or low-frequency program of six weeks (10 or 2 exercise sessions per week of 2 h, respectively). Functional capacity and QoL were assessed before and after cardiac rehabilitation. Global costs were also compared. RESULTS Compared with baseline, mean exercise capacity increased in both programs: for high- and low-frequency, respectively: peak VO2 = 15% and 12%, Wmax = 18% and 12%, VAT = 35% and 12% (all p < 0.001). However, when the programs were compared, only VAT increased significantly more during the high-frequency program (p = 0.002). During the high-frequency program, QoL increased slightly more, and more individuals improved in subjective physical functioning (p = 0.014). We observed superiority of the high-frequency program, especially in younger patients. Mean costs were estimated at 4,455 and 2,273 Euro, respectively, for the high- and low-frequency programs. CONCLUSIONS High-frequency exercise training is more effective in terms of VAT and QoL, but peak VO2 improves equally in both programs. Younger patients seem to benefit more from the high-frequency training.

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.

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.

Individual assessment of intensity-level for exercise training in patients with coronary artery disease is necessary

BACKGROUND Target intensity-level of exercise training in patients with coronary artery disease is adjusted usually by a target heart rate (THR). This THR is aimed to be at or nearby the anaerobic threshold (AT) and is calculated commonly from parameters of regular exercise training, instead of an actual measurement of AT and its related heart rate. Therefore, this study evaluated whether a calculation is reliable. METHODS In 91 male patients (age 52+/-9 years) exercise capacity was measured after a recent (>4 weeks) coronary event. AT was compared with peak exercise capacity and heart rate at AT was compared with THR, using the Karvonen method. RESULTS Mean AT (18.2 ml/min/kg, range 9.2-32.2) and mean peak V(O2) (24.5, range 10.9-43.9) were slightly decreased (respectively 0.83 and 0.79 of predicted). When related to peak exercise capacity, AT showed a large inter-individual variation. For example, heart rate at AT ranged from 0.55 to 0.96 of peak heart rate. As a result heart rate at AT varied considerably with THR. The mean THR, although significantly higher, correlated well with mean heart rate at AT (respectively, 109 and 105/min, P<0.01; r=0.86, P<0.001). However, in an important number of patients heart rate at AT was more than 10% below or above THR (respectively, 30 and 7%). CONCLUSION In individual exercise prescription for cardiac rehabilitation the training level should be determined directly, and not indirectly by calculation from heart rate parameters of exercise testing.

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.

Boussignac continuous positive airway pressure for the management of acute cardiogenic pulmonary edema: prospective study with a retrospective control group

BackgroundContinuous positive airway pressure (CPAP) treatment for acute cardiogenic pulmonary edema can have important benefits in acute cardiac care. However, coronary care units are usually not equipped and their personnel not adequately trained for applying CPAP with mechanical ventilators. Therefore we investigated in the coronary care unit setting the feasibility and outcome of the simple Boussignac mask-CPAP (BCPAP) system that does not need a mechanical ventilator.MethodsBCPAP was introduced in a coronary care unit where staff had no CPAP experience. All consecutive patients transported to our hospital with acute cardiogenic pulmonary edema, a respiratory rate > 25 breaths/min and a peripheral arterial oxygen saturation of < 95% while receiving oxygen, were included in a prospective BCPAP group that was compared with a historical control group that received conventional treatment with oxygen alone.ResultsDuring the 2-year prospective BCPAP study period 108 patients were admitted with acute cardiogenic pulmonary edema. Eighty-four of these patients (78%) were treated at the coronary care unit of which 66 (61%) were treated with BCPAP. During the control period 66 patients were admitted over a 1-year period of whom 31 (47%) needed respiratory support in the intensive care unit. BCPAP treatment was associated with a reduced hospital length of stay and fewer transfers to the intensive care unit for intubation and mechanical ventilation. Overall estimated savings of approximately € 3,800 per patient were achieved with the BCPAP strategy compared to conventional treatment.ConclusionAt the coronary care unit, BCPAP was feasible, medically effective, and cost-effective in the treatment of acute cardiogenic pulmonary edema. Endpoints included mortality, coronary care unit and hospital length of stay, need of ventilatory support, and cost (savings).

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.

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.