Arrhythmia monitoring and outcome after myocardial infarction (BIO|GUARD-MI): a randomized trial.

Objectives: Cardiac arrhythmias predict poor outcome after myocardial infarction (MI). We studied if arrhythmia monitoring with an insertable cardiac monitor (ICM) can improve treatment and outcome. Design: BIO|GUARD-MI was a randomized, international open-label study with blinded outcome assessment. Setting: Tertiary care facilities monitored the arrhythmias, while the follow-up remained with primary care physicians. Participants: Patients after ST-elevation (STEMI) or non-ST-elevation MI with an ejection fraction >35% and a CHA2DS2-VASc score ≥4 (men) or ≥5 (women). Interventions: Patients were randomly assigned to receive or not receive an ICM in addition to standard post-MI treatment. Device-detected arrhythmias triggered immediate guideline recommended therapy changes via remote monitoring. Main outcome measures: MACE, defined as a composite of cardiovascular death or acute unscheduled hospitalization for cardiovascular causes. Results: 790 patients (mean age 71 years, 72% male, 51% non-STEMI) of planned 1,400 pts were enrolled and followed for a median of 31.6 months. At 2 years, 39.4% of the device group and 6.7% of the control group had their therapy adapted for an arrhythmia [hazard ratio (HR) = 5.9, P < 0.0001]. Most frequent arrhythmias were atrial fibrillation, pauses and bradycardia. The use of an ICM did not improve outcome in the entire cohort (HR = 0.84, 95%-CI: 0.65-1.10; P = 0.21). In secondary analysis, a statistically significant interaction of the type of infarction suggests a benefit in the pre-specified non-STEMI subgroup. Risk factor analysis indicates that this may be connected to the higher incidence of MACE in patients with non-STEMI. Conclusions: The burden of asymptomatic but actionable arrhythmias is large in post-infarction patients. However, arrhythmia monitoring with an ICM did not improve outcome in the entire cohort. Post-hoc analysis suggests that it may be beneficial in non-STEMI patients or other high-risk subgroups. Clinical Trial Registration: [https://www.clinicaltrials.gov/ct2/show/NCT02341534], NCT02341534.

Atrial pacing minimization in sinus node dysfunction and risk of incident atrial fibrillation: a randomized trial.

BACKGROUND AND AIMS: High percentages of atrial pacing have been associated with an increased risk of atrial fibrillation. This study is aimed at evaluating whether atrial pacing minimization in patients with sinus node dysfunction reduces the incidence of atrial fibrillation. METHODS: In a nationwide, randomized controlled trial, 540 patients with sinus node dysfunction and an indication for first pacemaker implantation were assigned to pacing programmed to a base rate of 60 bpm and rate-adaptive pacing (DDDR-60) or pacing programmed to a base rate of 40 bpm without rate-adaptive pacing (DDD-40). Patients were followed on remote monitoring for 2 years. The primary endpoint was time to first episode of atrial fibrillation longer than 6 min. Secondary endpoints included longer episodes of atrial fibrillation, and the safety endpoint comprised a composite of syncope or presyncope. RESULTS: The median percentage of atrial pacing was 1% in patients assigned to DDD-40 and 49% in patients assigned to DDDR-60. The primary endpoint occurred in 124 patients (46%) in each treatment group (hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.76-1.25, P = .83). There were no between-group differences in atrial fibrillation exceeding 6 or 24 h, persistent atrial fibrillation, or cardioversions for atrial fibrillation. The incidence of syncope or presyncope was higher in patients assigned to DDD-40 (HR 1.71, 95% CI 1.13-2.59, P = .01). CONCLUSIONS: Atrial pacing minimization in patients with sinus node dysfunction does not reduce the incidence of atrial fibrillation. Programming a base rate of 40 bpm without rate-adaptive pacing is associated with an increased risk of syncope or presyncope.

Transmission and loss of ECG snapshots: Remote monitoring in implantable cardiac monitors.

INTRODUCTION: Remote monitoring including transmission of electrocardiogram (ECG) strips has been implemented in implantable cardiac monitors (ICM). We appraise whether the physician can rely on remote monitoring to be informed of all possibly significant arrhythmias. METHODS: We analyzed remote monitoring transmissions of patients in the ongoing BIO|GUARD-MI study, in which Biotronik devices are used. Once per day, the devices automatically transmit messages with up to six ECG snapshots to the Home Monitoring Service Center. If more than one type of arrhythmia is recorded during a day, at least one ECG of each arrhythmia type is transmitted. RESULTS: 212 study patients were registered at the service center. The mean age of the patients was 70 ±â€¯8 years, and 74% were male. Patients were followed for an average of 13 months. The median time from device implantation until the first message receipt in the service center was 2 days. The median patient-individual transmission success was 98.0% (IQR 93.6-99.8) and remained stable in the second and third year. The most frequent arrhythmias were atrial fibrillation, bradycardia and high ventricular rate. 17.3% of the messages with ECG snapshots contained more than one arrhythmia type. DISCUSSION: Our analysis confirms that the physician can rely on Home Monitoring to be informed of all possibly significant arrhythmias during long-term follow-up. We have found hints that the transmission of only one episode per day may lead to the loss of clinically relevant information if patients with ICMs are followed by remote monitoring only.

Adherence to dabigatran etexilate in atrial fibrillation patients intended to undergo electrical cardioversion.

AIMS: Effective anticoagulation in patients undergoing electrical cardioversion (ECV) for symptomatic atrial fibrillation is important to prevent adverse events. High medication adherence is a requirement. In patients with newly diagnosed atrial fibrillation (n = 169) who were intended to undergo ECV, the aim of this study was to measure self-reported short- and long-term adherence, evaluate whether dabigatran plasma concentrations reflect adherence, measure treatment satisfaction and assess whether adherence and treatment satisfaction are correlated. METHODS AND RESULTS: Plasma concentrations (liquid-chromatography tandem mass spectrometry), the 8-point Morisky Medication Adherence Scale (MMAS-8) and the Anti-Clot Treatment Scale (ACTS) were measured after 3 weeks and 7 weeks of treatment. Combined mean peak (1-3 h after intake) and trough (10-16 h after intake) plasma concentrations were 175 (SD 109) ng/mL and 75 (SD 45) ng/mL, respectively. There was no relationship between short-term adherence (last 3 days) or long-term adherence (last 3-4 weeks) and plasma concentrations, unless the last intake was more than 48 h ago. After 7 weeks high, moderate, and low adherence, according to the MMAS-8, was seen in 74%, 21%, and 5% of patients, respectively. Treatment satisfaction was high (median ACTS score 68.5, range 46-75 points). Treatment satisfaction and adherence were not correlated. CONCLUSION: The percentage of patients in the high adherence group (74%) was lower than expected, which is a matter of concern. Dabigatran plasma concentrations could not detect short- or long-term non-adherence, unless the drug was last taken more than 48 h ago. Treatment satisfaction did not correlate with adherence.

Cholestatic liver injury as a side-effect of dabigatran and the use of coagulation tests in dabigatran intoxication and after reversal by idarucizumab in bleeding and sepsis.

Idarucizumab, an antidote specific for dabigatran, became available recently. Dabigatran is not associated with increased risk of hepatotoxicity in comparison with warfarin, but it is seen as a rare side-effect. Cases of cholestatic liver injury due to dabigatran have not been reported previously. We present a case of severe gastro-intestinal bleeding with underlying dabigatran intoxication in a patient with renal failure and the effect of reversal of dabigatran using idaruzicumab on coagulation assays. International normalized ratio (INR) and activated partial thromboplastin time (APTT) results were elevated in a setting of sepsis, possibly due to liver failure. INR and APTT can be elevated if sepsis is complicated by disseminated intravascular coagulation (DIC) or liver failure, making it challenging to determine dabigatrans contribution to their prolongation. A rebound effect after administration of idarucizumab and slow elimination of dabigatran due to reduced kidney function could be detected using the Hemoclot® diluted thrombin time (dTT) in this situation, in contrast to with non-dilutional assays. Before admission, cholestatic liver injury started shortly after initiation of dabigatran etexilate therapy. As no other cause was found, this liver injury was likely to be drug-induced. Bleeding cessated promptly after administration of idarucizumab in dabigatran intoxication. In conclusion, the anticoagulant effect of dabigatran can be measured by Hemoclot® dTT in sepsis and cholestatic liver injury was seen as a possible rare side-effect of dabigatran treatment.

Enhanced external counterpulsation - effect on angina pectoris, QoL and exercise capacity after 1 year.

UNLABELLED: Enhanced external counterpulsation (EECP) is a new therapy offered to patients with refractory angina pectoris (AP). PURPOSE: To assess the effect of EECP on AP, quality of life (QoL) and exercise capacity in a design starting with a control period to avoid the influence of regression-towards-the-mean. METHODS: Patients were examined two months before EECP, just before, just after, and three and 12 months after EECP. EECP was given for 1 h 5 days a week in 7 weeks. Three sets of pneumatic cuffs were mounted on the lower extremities and inflated sequentially in diastole to 260 mm Hg. RESULTS: 50 patients were included (male 72%, mean age: 62.5 years). Mean daily AP attacks were reduced during EECP from 2.7 to 0.9 (p < 0.005) and the Canadian Cardiovascular Society classification was reduced by at least 1 class in 82% just after EECP, 79% 3 months and 76% 12 months after EECP (p < 0.0002). Generic (SF36) and disease-specific QoL (Seattle AP questionnaire) improved just after, 3 and 12 months after compared with that before EECP. There was a significant improvement in exercise capacity and exercise-induced chest pain just after, three and 12 months after EECP (p < 0.02). No change was detected during the control period. CONCLUSIONS: EECP improves generic and disease-specific QoL, angina intensity and exercise capacity in at least 12 months.

Implantable loop recorder is an effective diagnostic tool for unexplained syncope.

INTRODUCTION: Patients with cardiac syncope have a significantly higher mortality than patients with syncope of non-cardiac causes, while patients with syncope of unknown aetiology constitute an intermediate risk group, presumably because this group is mixed, which suggests that further diagnostic testing is warranted. MATERIAL AND METHODS: This was a retrospective single-centre study evaluating the diagnostic yield of an implantable loop recorder (ILR) in establishing the cause of recurrent, unexplained syncope. RESULTS: A total of 44 patients received ILR between 2007 and 2011. Follow-up data were available for 39 patients, the mean age was 63 years (range 23-94 years), 59% were female and the mean follow-up period was 349 days. The average time to first recurrence of syncope with ECG documentation was 244 days (range 11-699 days). The mean follow-up for the total population was 349 days (range 11-1,083 days) and for the group without recurrence 460 days (range 176-1,083 days). Diagnoses were obtained in 22 patients (56%) of which the cause of syncope was cardiac in 64%. CONCLUSION: ILR was an effective tool to establish an arrhythmic cause of the recurrent, unexplained syncope, and useful in ruling out arrhythmia as a cause of syncope. New studies are needed to demonstrate whether very prolonged monitoring in case of absent recurrence may further improve the diagnostic yield. Additionally, there is much need for randomized controlled trials to investigate whether ILR-guided therapy reduces recurrence rate and mortality. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

Short and long-term outcome in diabetic patients with acute myocardial infarction in the invasive era.

OBJECTIVES: To investigate the outcome after acute myocardial infarction in diabetic patients compared with non-diabetic patients in a period with invasive treatment as the preferred treatment for acute myocardial infarction (MI). DESIGN: Patient records for all patients admitted with an acute MI in a two-year period from July 1, 2001 to June 30, 2003 were reviewed. RESULTS: A total of 334 patients entered the study: 48 with diabetes mellitus (DM) and 286 without diabetes. ST-elevation infarction occurred in 49% of non-diabetic patients and 36% of diabetic patients. In-hospital mortality was 23% among diabetic patients compared to 5% among non-diabetic patients (p < 0.001). Long-term mortality (median 2 years and 10 months) was 44% in diabetic-patients and 23% in non-diabetic patients (p = 0.001). Diabetic patients were older, more frequently had hypertension and three-vessel disease, but DM was found to be an independent risk factor for death after MI (p = 0.005). CONCLUSIONS: In an era of invasive therapy as the preferred therapy for acute MI, DM is still associated with considerably increased mortality after an acute MI.

Non-invasive estimation of shunt and ventilation-perfusion mismatch.

OBJECTIVE: To investigate whether parameters describing pulmonary gas exchange (shunt and ventilation-perfusion mismatch) can be estimated consistently by the use of non-invasive data as input to a mathematical model of oxygen transport. DESIGN: Prospective study. SETTING: Investigations were carried out in the post-anaesthesia care unit, coronary care unit, and intensive care unit. PATIENTS: Data from ninety-five patients and six normal subjects were included for the comparison. The clinical situations differed, ranging from healthy subjects to patients with acute respiratory failure in the intensive care unit. MEASUREMENTS: The experimental procedure involved changing the inspired oxygen fraction (F(I)O(2)) in 4-6 steps in order to obtain arterial oxygen saturations (S(a)O(2)) in the range from 90-100%. This procedure allows plotting a F(I)O(2)/S(a)O(2) or F(E)O(2)/S(a)O(2) curve, the shape and position of which was quantified using the mathematical model estimating pulmonary shunt and a measure of ventilation-perfusion mismatch (DeltaPO(2)). This procedure was performed using either arterial blood samples at each F(I)O(2) level (invasive approach) or using values from the pulse oximeter (non-invasive approach). MAIN RESULTS: The model provided good fit to data using both the invasive and non-invasive experimental approach. The parameter estimates were linearly correlated with highly significant correlation coefficients; shunt(invasive) vs shunt(non-invasive), r(2) = 0.74, P <0.01, and DeltaPO(2)(invasive) vs DeltaPO(2)(non-invasive), r(2) = 0.97, P <0.001. CONCLUSIONS: Pulmonary gas exchange can be described equally well using non-invasive data. The simplicity of the non-invasive approach makes the method suitable for large-scale clinical use.

The automatic lung parameter estimator (ALPE) system: non-invasive estimation of pulmonary gas exchange parameters in 10-15 minutes.

OBJECTIVE: Clinical measurements of pulmonary gas exchange abnormalities might help prevent hypoxaemia and be useful in monitoring the effects of therapy. In clinical practice single parameters are often used to describe the abnormality e.g., the "effective shunt." A single parameter description is often insufficient, lumping the effects of several abnormalities. A more detailed picture can be obtained from experiments where FiO2 is varied and two parameters estimated. These experiments have previously taken 30-40 minutes to complete, making them inappropriate for routine clinical use. However with automation of data collection and parameter estimation, the experimental time can be reduced to 10-15 minutes. METHODS: A system has been built for non-invasive, Automatic, Lung Parameter Estimation (ALPE). This system consists of a ventilator, a gas analyser with pulse oximeter, and a computer. Computer programs control the experimental procedure, collect data from the ventilator and gas analyser, and estimate pulmonary gas exchange parameters. Use of the ALPE system, i.e. in estimating gas exchange parameters and reducing experimental time, has been tested on five normal subjects, two patients before and during diuretic therapy, and on 50 occasions in patients before and after surgical intervention. RESULTS: The ALPE system provides estimation of pulmonary gas exchange parameters from a simple, clinical, non-invasive procedure, automatically and quickly. For normal subjects and in patients receiving diuretic therapy, data collection by clinicians familiar with ALPE took (mean +/- SD) 13 min 40 sec +/- 1 min 23 sec. For studies on patients before and after surgery, data collection by an intensive care nurse took (mean +/- SD) 10 min 47 sec +/- 2 min 14 sec. Parameter estimates were: for normal subjects, shunt = 4.95% +/- 2.64% and fA2 = 0.89 +/- 0.01; for patients with heart failure prior to diuretic therapy, patient 1, shunt = 11.50% fA2 = 0.41, patient 2 shunt = 11.61% fA2 = 0.55; and during therapy: patient 1, shunt = 11.51% fA2 = 0.71, patient 2, shunt = 11.22% fA2 = 0.49. CONCLUSIONS: The ALPE system provides quick, non-invasive estimation of pulmonary gas exchange parameters and may have several clinical applications. These include, monitoring pulmonary gas exchange abnormalities in the ICU, assessing post-operative gas exchange abnormalities, and titrating diuretic therapy in patients with heart failure.