Clinical and financial impact of sleep disordered breathing on heart failure admissions.

BACKGROUND: The impact of sleep disordered breathing (SDB) on heart failure (HF) is increasingly recognized. However, limited data exist in support of quantification of the clinical and financial impact of SDB on HF hospitalizations. METHODS: A sleep-heart registry included all patients who underwent inpatient sleep testing during hospitalization for HF at a single cardiac center. Readmission data and actual costs of readmissions were obtained from the institutional honest broker. Patients were classified based on the inpatient sleep study as having no SDB, obstructive sleep apnea (OSA), or central sleep apnea (CSA). Cumulative cardiac readmission rates and costs through 3 and 6 months post-discharge were calculated. Unadjusted and adjusted (age, sex, body mass index, and left ventricular ejection fraction) modeling of cost was performed. RESULTS: The cohort consisted of 1547 patients, 393 (25%) had no SDB, 438 (28%) had CSA, and 716 (46%) had OSA. Within 6 months of discharge, 195 CSA patients (45%), 264 OSA patients (37%), and 109 no SDB patients (28%) required cardiovascular readmissions. Similarly, 3- and 6-month mortality rates were higher in both SDB groups than those with no SDB. Both unadjusted and adjusted readmission costs were higher in the OSA and CSA groups compared to no SDB group at 3 and 6 months post-discharge with the CSA and OSA group costs nearly double (~ $16,000) the no SDB group (~ $9000) through 6 months. INTERPRETATION: Previously undiagnosed OSA and CSA are common in patients hospitalized with HF and are associated with increased readmissions rate and mortality.

Uncovering interim clinical events at the time of clinical encounter by reviewing intrathoracic impedance threshold crossings.

BACKGROUND: Acute decreases in intrathoracic impedance monitored by implanted devices have been shown to precede heart failure exacerbations, although there is still debate regarding its clinical utility in predicting and preventing future events. However, the usefulness of such information to direct patient encounter and enhance patient recall of relevant preceding clinical events at the point of care has not been carefully examined. METHODS AND RESULTS: In this multicenter study, we interviewed 326 patients with heart failure who received an implanted device with intrathoracic impedance-monitoring capabilities both before and after device information was reviewed. We compared the self-reported clinically relevant events (including heart failure hospitalizations, signs and symptoms of worsening heart failure, changes in diuretic therapy, or other fluid-related events) obtained before and after device interrogation, and then examined the relationship between such events with impedance trends documented by the devices. Over 333 ± 96 days of device monitoring, 215 of 326 patients experienced 590 intrathoracic impedance fluid index threshold-crossing events at the nominal threshold value (60 Ω-d). Review of device-derived information led to the discovery of 221 (37%) previously unreported clinically relevant events in 138 subjects. This included 60 subjects not previously identified as having had clinically relevant events (or 35% of the 171 subjects who did not report events). CONCLUSIONS: Our data demonstrated that reviewing device-derived intrathoracic impedance trends at the time of clinical encounter may help uncover self-reporting of potential clinically relevant events.

Controversies in cardiac resynchronization therapy: do sex differences in response exist?

Cardiac resynchronization therapy (CRT) is well established in the treatment of patients with heart failure, but lacks data addressing sex differences in response. Women with heart failure outnumber men, but have additional comorbidities and typically are older. Women continue to be underrepresented in clinical trials, but examining their response to a therapy across multiple studies could provide significant insight into the treatment effect. The major clinical trials did have a significant percentage of female patients, but present minimal in subgroup analysis. A few small studies comparing the effect of CRT between men and women indicate a more positive effect in women. This early data suggests CRT is at least as effective in women as it is in men, and may have additional benefit in this population.

Transvenous phrenic nerve stimulation for central sleep apnea is safe and effective in patients with concomitant cardiac devices.

BACKGROUND: Central sleep apnea is common in heart failure patients. Transvenous phrenic nerve stimulation (TPNS) requires placing a lead to stimulate the phrenic nerve and activate the diaphragm. Data are lacking concerning the safety and efficacy of TPNS in patients with concomitant cardiovascular implantable electronic devices (CIEDs). OBJECTIVE: To report the safety and efficacy of TPNS in patients with concomitant CIEDs. METHODS: In the remede System Pivotal Trial, 151 patients underwent TPNS device implant. This analysis compared patients with concomitant CIEDs to those without with respect to safety, implant metrics, and efficacy of TPNS. Safety was assessed using incidence of adverse events and device-device interactions. A detailed interaction protocol was followed. Implant metrics included overall TPNS implantation success. Efficacy endpoints included changes in the apnea-hypopnea index (AHI) and quality of life. RESULTS: Of 151 patients, 64 (42%) had a concomitant CIED. There were no significant differences between the groups with respect to safety. There were 4 CIED oversensing events in 3 patients leading to 1 inappropriate defibrillator shock and delivery of antitachycardia pacing. There was no difference in efficacy between the CIED and non-CIED subgroups receiving TPNS, with both having similar percentages of patients who achieved ≥50% reduction in AHI and quality-of-life improvement. CONCLUSION: Concomitant CIED and TPNS therapy is safe. The presence of a concomitant CIED did not seem to impact implant metrics, implantation success, and TPNS efficacy. A detailed interaction protocol should be followed to minimize the incidence of device-device interaction.

Novel phrenic nerve stimulator treats Cheyne-Stokes respiration: polysomnographic insights.

None: A symptomatic patient with atrial fibrillation and Cheyne-Stokes respiration (CSR) was implanted with a transvenous phrenic nerve stimulation (TPNS) device-the remede System-that is indicated for adult patients with moderate to severe central sleep apnea. Sleep recordings demonstrated that TPNS eliminated periodic breathing by activating the diaphragm and stabilizing respiratory patterns. These recordings of preprogrammed periods on versus off TPNS illustrate prompt (1) stabilization of tidal airflow, respiratory effort, and oxygenation as stimulation amplitude increased stepwise and (2) recurrence of CSR immediately after TPNS deactivated. Despite differences in respiratory patterns, minute ventilation was comparable during periods on and off TPNS. These findings suggest that diaphragmatic pacing entrains ventilation without disrupting sleep, accounting for observed improvements in periodic breathing, gas exchange, sleep architecture, and quality of life. Effective means to relieve CSR could potentially mitigate nocturnal cardiovascular stress and disease progression.

In patients with heart failure the burden of central sleep apnea increases in the late sleep hours.

Study Objectives: Periodic breathing with central sleep apnea (CSA) is common in patients with left ventricular systolic dysfunction. Based on the pathophysiological mechanisms underlying CSA, we hypothesized that the frequency of CSA episodes would increase in the late hours of non-rapid eye movement (NREM) of sleep. Methods: Forty-one patients with left ventricular ejection fraction <40% underwent full-night-attended polysomnography scored by a central core lab. Because central apneas occur primarily in NREM sleep, total NREM sleep time for each patient was divided into 8 equal duration segments. Segment event counts were normalized to an events/hour index based on sleep segment duration. Results: Central apnea index (CAI) varied among sleep segments (p = 0.001). As expected CAI was higher in segment 1 compared to segments 2 and 3, increasing during later segments. The minimum CAI occurred in segment 2 with mean ± SD of 21 ± 3 events/hour and maximum CAI was in segment 8 with 37 ± 4 events/hour. We also determined central apnea duration which varied among segments (p = 0.005), with longer durations later in the night (segment 1: 22 ± 1 seconds; segment 8: 26 ± 1 seconds, p < 0.001). Data were also analyzed including rapid eye movement (REM) sleep, with similar results. Further, comparison of CAI between the first and second half of the night showed a significant increase in the index. Circulation time did not change across the segments (p = 0.073). Conclusions: In patients with left ventricular dysfunction and CSA, central apnea burden (number and duration) increases during later hours of sleep. These findings have pathophysiological and therapeutic implications. Clinical Trial Registration: NCT01124370.

The evaluation and monitoring of volume status in congestive heart failure.

The increasing prevalence of heart failure dictates that physicians effectively assess and treat congestion. The evaluation of volume status in the complex group of patients with heart failure is very challenging. Physical examination is at best challenging and not always helpful, confounded by body habitus and comorbidities. Weight monitoring has been shown to be helpful, especially in combination with remote monitoring or telephonic checks. Invasive methods such as pulmonary artery catheters provide significant information but have not been proven to be clinically effective. Noninvasive measures such as impedance cardiography and echocardiography provide additional information. The future of heart failure management may reside in implantable monitors, either alone or in combination with other intracardiac devices. These monitors can provide surrogates of pulmonary capillary wedge pressure and volume. They can also be followed remotely and provide information on the patient's status more frequently than office visits. This manuscript will review volume assessment including past, current, and future methods.

Effect of heart failure exacerbations on anticoagulation: a prospective, observational, pilot cohort study.

BACKGROUND: Some studies have suggested that heart failure (HF) is associated with excessive anticoagulation, but definitive data or data showing causation do not exist. Knowledge of risk factors for excessive anticoagulation is critical to manage warfarin therapy safely. OBJECTIVE: This study characterized the relation between HF-associated hypervolemia and excessive anticoagulation in patients with HF taking chronic warfarin therapy. METHODS: This was a prospective, observational pilot study conducted in a university-based HF clinic. Patients aged 18 to 85 years with HF and taking warfarin were enrolled and were observed for episodes of hypervolemia. Hypervolemia was determined based on multiple clinical factors, including patient-reported symptoms and physical examination. Anticoagulation was assessed longitudinally per standard of care by measurement of the international normalized ratio (INR). A chi(2) analysis was used to determine whether hypervolemia was associated with an increased risk of excessive anticoagulation. Paired and unpaired t tests were used for ad hoc analyses. RESULTS: Forty patients with 41 HF episodes who were taking warfarin were enrolled between December 2003 and July 2007. Mean (SD) age was 67.2 (11.1) years and mean weight was 218.5 (62.8) pounds; 29 patients (72.5%) were men and 34 (85.0%) were white. Most had systolic dysfunction (n = 26; 65.0%) and were taking warfarin for atrial fibrillation (n = 33; 82.5%); the mean weekly warfarin dose was 30.8 (17.5) mg. There were 41 evaluable hypervolemia episodes over a mean follow-up of 14.5 (9.0) months. The mean INR change during hypervolemia was -0.02 (0.82) INR unit (P = NS vs baseline). No association was found between hypervolemia episodes and INR increases of > or =50% (P = NS); the results remained nonsignificant for both diastolic and systolic HF when analyzed separately. There was no significant change from baseline INR between patients classified with mild, moderate, or severe hypervolemia or between patients classified according to New York Heart Association (NYHA) functional class (all, P = NS). Patients with NYHA class III had a lower weekly warfarin dose than those with NYHA class II (25.73 vs 31.75 mg; P < 0.01). CONCLUSION: Mild hypervolemia did not appear to be related to excessive anticoagulation in these patients with HF taking chronic warfarin therapy.

Candesartan in heart failure.

Candesartan cilexetil is a nonpeptide selective blocker of the angiotensin II receptor sub-type 1. It is a prodrug that is converted to its active metabolite during its variable absorption. It is highly protein bound with a small volume of distribution and a nine-hour half-life. Candesartan is one of two angiotensin receptor blockers approved for use in heart failure. MEDLINE was searched using OVID and PubMed to evaluate the evidence for using candesartan in patients with heart failure. Pharmacologic and pharmacokinetic evaluations, as well as clinical trials, were selected and are presented in this review. Clinical evidence supports the indication for use in systolic heart failure. Results for use in patients with diastolic heart failure were non-significant. Candesartan was well tolerated in the trials, with hyperkalemia, renal dysfunction, and hypotension being the most common adverse events. Use of angiotensin receptor blockers with angiotensin-converting enzyme inhibitors needs further study; however, candesartan appears to provide added benefit in this setting. Candesartan is a safe and effective option for patients with systolic heart failure. Data regarding other angiotensin receptor blockers is underway.