Philip B. Adamson

Wireless pulmonary artery haemodynamic monitoring in chronic heart failure: a randomised controlled trial

BACKGROUND Results of previous studies support the hypothesis that implantable haemodynamic monitoring systems might reduce rates of hospitalisation in patients with heart failure. We undertook a single-blind trial to assess this approach. METHODS Patients with New York Heart Association (NYHA) class III heart failure, irrespective of the left ventricular ejection fraction, and a previous hospital admission for heart failure were enrolled in 64 centres in the USA. They were randomly assigned by use of a centralised electronic system to management with a wireless implantable haemodynamic monitoring (W-IHM) system (treatment group) or to a control group for at least 6 months. Only patients were masked to their assignment group. In the treatment group, clinicians used daily measurement of pulmonary artery pressures in addition to standard of care versus standard of care alone in the control group. The primary efficacy endpoint was the rate of heart-failure-related hospitalisations at 6 months. The safety endpoints assessed at 6 months were freedom from device-related or system-related complications (DSRC) and freedom from pressure-sensor failures. All analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00531661. FINDINGS In 6 months, 83 heart-failure-related hospitalisations were reported in the treatment group (n=270) compared with 120 in the control group (n=280; rate 0·31 vs 0·44, hazard ratio [HR] 0·70, 95% CI 0·60-0·84, p<0·0001). During the entire follow-up (mean 15 months [SD 7]), the treatment group had a 39% reduction in heart-failure-related hospitalisation compared with the control group (153 vs 253, HR 0·64, 95% CI 0·55-0·75; p<0·0001). Eight patients had DSRC and overall freedom from DSRC was 98·6% (97·3-99·4) compared with a prespecified performance criterion of 80% (p<0·0001); and overall freedom from pressure-sensor failures was 100% (99·3-100·0). INTERPRETATION Our results are consistent with, and extend, previous findings by definitively showing a significant and large reduction in hospitalisation for patients with NYHA class III heart failure who were managed with a wireless implantable haemodynamic monitoring system. The addition of information about pulmonary artery pressure to clinical signs and symptoms allows for improved heart failure management. FUNDING CardioMEMS.

Biventricular pacing for atrioventricular block and systolic dysfunction.

BACKGROUND Right ventricular pacing restores an adequate heart rate in patients with atrioventricular block, but high percentages of right ventricular apical pacing may promote left ventricular systolic dysfunction. We evaluated whether biventricular pacing might reduce mortality, morbidity, and adverse left ventricular remodeling in such patients. METHODS We enrolled patients who had indications for pacing with atrioventricular block; New York Heart Association (NYHA) class I, II, or III heart failure; and a left ventricular ejection fraction of 50% or less. Patients received a cardiac-resynchronization pacemaker or implantable cardioverter-defibrillator (ICD) (the latter if the patient had an indication for defibrillation therapy) and were randomly assigned to standard right ventricular pacing or biventricular pacing. The primary outcome was the time to death from any cause, an urgent care visit for heart failure that required intravenous therapy, or a 15% or more increase in the left ventricular end-systolic volume index. RESULTS Of 918 patients enrolled, 691 underwent randomization and were followed for an average of 37 months. The primary outcome occurred in 190 of 342 patients (55.6%) in the right-ventricular-pacing group, as compared with 160 of 349 (45.8%) in the biventricular-pacing group. Patients randomly assigned to biventricular pacing had a significantly lower incidence of the primary outcome over time than did those assigned to right ventricular pacing (hazard ratio, 0.74; 95% credible interval, 0.60 to 0.90); results were similar in the pacemaker and ICD groups. Left ventricular lead-related complications occurred in 6.4% of patients. CONCLUSIONS Biventricular pacing was superior to conventional right ventricular pacing in patients with atrioventricular block and left ventricular systolic dysfunction with NYHA class I, II, or III heart failure. (Funded by Medtronic; BLOCK HF ClinicalTrials.gov number, NCT00267098.).

Continuous Autonomic Assessment in Patients With Symptomatic Heart Failure Prognostic Value of Heart Rate Variability Measured by an Implanted Cardiac Resynchronization Device

Background—Heart rate variability (HRV) as an indirect autonomic assessment provides prognostic information when measured over short time periods in patients with heart failure. Long-term continuous HRV can be measured from an implantable device, but the clinical value of these measurements is unknown. Methods and Results—A total of 397 patients with New York Heart Association class III or IV heart failure were studied. Of these, 370 patients had information from their implanted cardiac resynchronization device for mortality risk stratification, and 288 patients had information for measured parameters (ie, HRV, night heart rate, and patient activity) and clinical event analyses. Continuous HRV was measured as the standard deviation of 5-minute median atrial-atrial intervals (SDAAM) sensed by the device. SDAAM <50 ms when averaged over 4 weeks was associated with increased mortality risk (hazard ratio 3.20, P=0.02) and SDAAM were persistently lower over the entire follow-up period in patients who required hospitalization or died. SDAAM decreased a median of 16 days before hospitalization and returned to baseline after treatment. Automated detection of decreases in SDAAM was 70% sensitive in detecting cardiovascular hospitalization, with 2.4 false-positives per patient-year of follow-up. Conclusions—This study demonstrates that SDAAM continuously measured from an implanted cardiac resynchronization device is lower in patients at high mortality and hospitalization risk. SDAAM declines as patient status decompensates. Continuous long-term SDAAM may be a useful tool in the clinical management of patients with chronic heart failure.

Exercise training confers anticipatory protection from sudden death during acute myocardial ischemia.

Seven conscious dogs documented to be at high risk by the occurrence of ventricular fibrillation (VF) during acute myocardial ischemia were randomly assigned to 6 weeks of either daily exercise training or cage rest followed by exercise training. After 6 weeks of daily treadmill training, heart rate variability, a marker of vagal tone, increased by 74% (P < .001); baroreflex sensitivity, a marker of the capability to reflexly augment vagal activity, increased by 69% (P < .01); the repetitive extrasystole threshold, a marker of ventricular electrical stability, increased by 44% (P < .05). After exercise training, the incidence of ventricular fibrillation during acute myocardial ischemia decreased by 100%, as all animals survived. Neither passage of time nor heart rate level during ischemia contributed to the outcome. The most likely mechanism to explain the striking change in risk status is the shift in autonomic balance characterized by increased cardiac vagal activity, which was previously shown to have an antifibrillatory effect. These results suggest that exercise training in healthy individuals may decrease their likelihood of developing lethal arrhythmias during acute myocardial ischemia.

Transition From Chronic Compensated to Acute Decompensated Heart Failure Pathophysiological Insights Obtained From Continuous Monitoring of Intracardiac Pressures

Background— Approximately half of all patients with chronic heart failure (HF) have a decreased ejection fraction (EF) (systolic HF [SHF]); the other half have HF with a normal EF (diastolic HF [DHF]). However, the underlying pathophysiological differences between DHF and SHF patients are incompletely defined. The purpose of this study was to use echocardiographic and implantable hemodynamic monitor data to examine the pathophysiology of chronic compensated and acute decompensated HF in SHF versus DHF patients. Methods and Results— Patients were divided into 2 subgroups: 204 had EF <50% (SHF) and 70 had EF ≥50% (DHF). DHF patients had EF of 58±8%, end-diastolic dimension of 50±10 mm, estimated resting pulmonary artery diastolic pressure (ePAD) of 16±9 mm Hg, and diastolic distensibility index (ratio of ePAD to end-diastolic volume) of 0.11±0.06 mm Hg/mL. In contrast, SHF patients had EF of 24±10%, end-diastolic dimension of 68±11 mm, ePAD of 18±7 mm Hg, and diastolic distensibility index of 0.06±0.04 mm Hg/mL (P<0.05 versus DHF for all variables except ePAD). In SHF and DHF patients who developed acute decompensated HF, these events were associated with a significant increase in ePAD, from 17±7 to 22±7 mm Hg (P<0.05) in DHF and from 21±9 to 24±8 mm Hg (P<0.05) in SHF. As a group, patients who did not have acute decompensated HF events had no significant changes in ePAD. Conclusions— Significant structural and functional differences were found between patients with SHF and those with DHF; however, elevated diastolic pressures play a pivotal role in the underlying pathophysiology of chronic compensated and acute decompensated HF in both SHF and DHF.

Heart Rate Variability During Specific Sleep Stages A Comparison of Healthy Subjects With Patients After Myocardial Infarction

BACKGROUND Heart rate variability (HRV) is typically higher during nighttime. This evidence supports the concept that overall, sleep is a condition during which vagal activity is dominant. Myocardial infarction (MI) results in a loss in the overall nocturnal HRV increase. However, the characteristics of HRV during specific sleep stages in normal subjects and, more importantly, after MI, are unknown. This study describes HRV during sleep stages in normal subjects and in patients with a recent MI. METHODS AND RESULTS HRV was measured from 5 minutes of continuous ECG recording in 8 subjects with no clinical evidence of coronary artery disease (age, 47 +/- 4 years) and in 8 patients with a recent MI (age, 51 +/- 2 years; NS versus control subjects) in the awake state, non-rapid eye movement (REM), and REM sleep. In normal subjects, the low- to high-frequency ratio (LF/HF) derived from power spectral analysis of HRV decreased significantly from the awake state to non-REM sleep (from 4 +/- 1.4 to 1.22 +/- 0.33, P < .01). During REM sleep, the LF/HF increased to 3 +/- 0.74 (P < .01 versus non-REM, NS versus awake). In post-MI patients, the LF/HF showed an opposite trend toward an increase from 2.4 +/- 0.7 to 5.11 +/- 1.4 (NS, P < .01 versus the control subjects). REM sleep produced a further increase in the LF/HF up to 8.9 +/- 1.6 (P < .01 versus awake and versus REM in control subjects). CONCLUSIONS Myocardial infarction causes a loss in the capability of the vagus to physiologically activate during sleep. This results in a condition of relative sympathetic dominance even in a situation such as sleep, normally described as a condition of vagal dominance and, consequently, low risk for lethal events. The evidence that the sleep-related vagal activation is lost after MI may provide new insights to understanding the nocturnal occurrence of sudden death.

2012 EHRA/HRS expert consensus statement on cardiac resynchronization therapy in heart failure: implant and follow-up recommendations and management

2012 EHRA/HRS expert consensus statement on cardiac resynchronization therapy in heart failure : implant and follow-up recommendations and management

Cardiac Resynchronization Therapy Improves Heart Rate Variability in Patients with Symptomatic Heart Failure

Background Cardiac resynchronization therapy (CRT) using biventricular pacing improves symptoms and functional capacity in patients with moderate to severe heart failure. The present study examined whether an improvement in ventricular performance from resynchronization therapy changes the autonomic control of heart rate. Methods and Results Heart rate variability (HRV) was examined in 50 patients implanted with the InSync biventricular pacing system who were randomized to therapy‐on (n=25) or therapy‐off (n=25). HRV was computed as the standard deviation of the atrial cycle length sensed from the system over 2 months of continuous monitoring. HRV was compared between CRT‐on and CRT‐off groups. HRV was higher in patients randomized to CRT‐on compared with CRT‐off (148±47 ms for CRT‐on versus 118±45 ms for CRT‐off; P=0.02), despite the lack of difference in mean atrial cycle length (844±129 ms for CRT‐on versus 851±110 ms for CRT‐off; P=0.82). Changes in plasma catecholamines were not different between the CRT‐on and CRT‐off groups from baseline to the 3‐month follow‐up. Conclusions Improvement in ventricular performance from CRT shifts cardiac autonomic balance toward a more favorable profile that is less dependent on sympathetic activation. (Circulation. 2003;108:266‐269.)

Heart rate variability before and after myocardial infarction in conscious dogs at high and low risk of sudden death.

Heart rate variability has been demonstrated both experimentally and clinically to be of prognostic importance in determining mortality after myocardial infarction. However, no paired studies have been reported to examine heart rate variability before and after myocardial infarction. The hypothesis was tested that low values of heart rate variability provided risk assessment both before and after myocardial infarction with use of an established canine model of sudden cardiac death. Risk for sudden death was assessed 1 month after myocardial infarction by a protocol in which exercise and myocardial ischemia were combined; dogs that developed ventricular fibrillation were classified at high risk for sudden death (susceptible) and the survivors were considered low risk (resistant). In resistant dogs, myocardial infarction did not affect any measure of heart rate variability: 1) mean RR interval, 2) standard deviation of the mean RR interval, and 3) the coefficient of variance (standard deviation/RR interval). By contrast, after myocardial infarction, susceptible dogs showed significant decrease in all measures of heart rate variability. Before myocardial infarction, no differences were seen between susceptible and resistant dogs. However, 30 days after infarction, epidemiologic analysis of the coefficient of variance showed high sensitivity and specificity (88% and 80%, respectively), predicting susceptibility. Therefore, results of analysis of 30 min of beat to beat heart period at rest 30 days after myocardial infarction are highly predictive for increased risk of sudden death.

Wireless Pulmonary Artery Pressure Monitoring Guides Management to Reduce Decompensation in Heart Failure with Preserved Ejection Fraction

Background—No treatment strategies have been demonstrated to be beneficial for the population for patients with heart failure (HF) and preserved ejection fraction (EF). Methods and Results—The CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients (CHAMPION) trial was a prospective, single-blinded, randomized controlled clinical trial testing the hypothesis that hemodynamically guided HF management decreases decompensation leading to hospitalization. Of the 550 patients enrolled in the study, 119 had left ventricular EF ≥40% (average, 50.6%), 430 patients had low left ventricular EF (<40%; average, 23.3%), and 1 patient had no documented left ventricular EF. A microelectromechanical system pressure sensor was permanently implanted in all participants during right heart catheterization. After implant, subjects were randomly assigned in single-blind fashion to a treatment group in whom daily uploaded pressures were used in a treatment strategy for HF management or to a control group in whom standard HF management included weight-monitoring, and pressures were uploaded but not available for investigator use. The primary efficacy end point of HF hospitalization rate >6 months for preserved EF patients was 46% lower in the treatment group compared with control (incidence rate ratio, 0.54; 95% confidence interval, 0.38–0.70; P<0.0001). After an average of 17.6 months of blinded follow-up, the hospitalization rate was 50% lower (incidence rate ratio, 0.50; 95% confidence interval, 0.35–0.70; P<0.0001). In response to pulmonary artery pressure information, more changes in diuretic and vasodilator therapies were made in the treatment group. Conclusions—Hemodynamically guided management of patients with HF with preserved EF reduced decompensation leading to hospitalization compared with standard HF management strategies. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00531661.