Clinical Implications of Brief Device-Detected Atrial Tachyarrhythmias in a Cardiac Rhythm Management Device Population: Results from the Registry of Atrial Tachycardia and Atrial Fibrillation Episodes.

BACKGROUND: The RATE Registry (Registry of Atrial Tachycardia and Atrial Fibrillation Episodes) is a prospective, outcomes-oriented registry designed to document the prevalence of atrial tachycardia and/or fibrillation (AT/AF) of any duration in patients with pacemakers and implantable cardioverter defibrillators (ICDs) and evaluate associations between rigorously adjudicated AT/AF and predefined clinical events, including stroke. The appropriate clinical response to brief episodes of AT/AF remains unclear. METHODS: Rigorously adjudicated electrogram (EGM) data were correlated with adjudicated clinical events with logistic regression and Cox models. Long episodes of AT/AF were defined as episodes in which the onset and/or offset of AT/AF was not present within a single EGM recording. Short episodes of AT/AF were defined as episodes in which both the onset and offset of AT/AF were present within a single EGM recording. RESULTS: We enrolled 5379 patients with pacemakers (N=3141) or ICDs (N=2238) at 225 US sites (median follow-up 22.9 months). There were 359 deaths. There were 478 hospitalizations among 342 patients for clinical events. We adjudicated 37 531 EGMs; 50% of patients had at least one episode of AT/AF. Patients with clinical events were more likely than those without to have long AT/AF (31.9% vs. 22.1% for pacemaker patients and 28.7% vs. 20.2% for ICD patients; P<0.05 for both groups). Only short episodes of AT/AF were documented in 9% of pacemaker patients and 16% of ICD patients. Patients with clinical events were no more likely than those without to have short AT/AF (5.1% vs. 7.9% for pacemaker patients and 11.5% vs. 10.4% for ICD patients; P=0.21 and 0.66, respectively). CONCLUSIONS: In the RATE Registry, rigorously adjudicated short episodes of AT/AF, as defined, were not associated with increased risk of clinical events compared with patients without documented AT/AF. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00837798.

Relaxin for treatment of acute heart failure: making the case for treating targeted patient profiles.

Patients presenting with acute heart failure (AHF) represent a heterogeneous population with respect to demographics, clinical profiles, and precipitating factors. Despite this, most clinical trials have treated the study population as a homogeneous group in an attempt to achieve adequate statistical power for endpoint analysis. This approach has proven to be of little value in the development of new agents for treatment of AHF. By contrast, the phase III clinical trial of relaxin focused on a subset of AHF patients who were normotensive or hypertensive and who had moderate renal impairment. The study patients, who were primarily from Eastern Europe, represented a population that would be expected to have less genetic variability than the study populations in larger multinational AHF trials. A focused study design targeting specific patient profiles should be considered for future clinical AHF trials that investigate new therapies or compare the effectiveness of existing therapies.

Targeting hyponatremia and hemodynamics in acute decompensated heart failure: is there a role for vasopressin antagonists?

Current treatment of acute decompensated heart failure (ADHF) has not reduced the significant morbidity or mortality associated with this disease, and has promoted drug development aimed at neurohormonal targets. Hypervolemic hyponatremia, which is linked to the nonosmotic release of arginine vasopressin, is associated with a poor prognosis in patients with heart failure (HF). Vasopressin acts on V(2) and V(1a) receptors to cause water retention and vasoconstriction, respectively. Clinical trials have demonstrated that vasopressin receptor antagonists (VRAs) are effective in treating hypervolemic hyponatremia in ADHF without a negative impact on renal function. The small hemodynamic benefit seen with VRA use appeared to result from V(2)-receptor antagonist-induced increase in urine output rather than from a vasodilatory drug effect. VRA use in ADHF trials was associated with minimal symptomatic improvement and no impact on morbidity or mortality. At present, clinical trial evidence does not support the routine use of VRAs in ADHF. Given the favorable renal profile of VRAs, studies on the possible benefit of VRAs in ADHF patients with renal insufficiency and diuretic resistance appear warranted.

Derivation and Validation of an In-Hospital Mortality Prediction Model Suitable for Profiling Hospital Performance in Heart Failure.

BACKGROUND: Comparing heart failure (HF) outcomes across hospitals requires adequate risk adjustment. We aimed to develop and validate a model that can be used to compare quality of HF care across hospitals. METHODS AND RESULTS: We included patients with HF aged ≥18 years admitted to one of 433 hospitals that participated in the Premier Inc Data Warehouse. This model (Premier) contained patient demographics, comorbidities, and acute conditions present on admission, derived from administrative and billing records. In a separate data set derived from electronic health records, we validated the Premier model by comparing hospital risk-standardized mortality rates calculated with the Premier model to those calculated with a validated clinical model containing laboratory data (LAPS [Laboratory-Based Acute Physiology Score]). Among the 200 832 admissions in the Premier Inc Data Warehouse, inpatient mortality was 4.0%. The model showed acceptable discrimination in the warehouse data (C statistic 0.75; 95% confidence interval, 0.74-0.76). In the validation data set, both the Premier model and the LAPS models showed acceptable discrimination (C statistic: Premier: 0.76 [95% confidence interval, 0.74-0.77]; LAPS: 0.78 [95% confidence interval, 0.76-0.80]). Risk-standardized mortality rates for both models ranged from 2% to 7%. A linear regression equation describing the association between Premier- and LAPS-specific mortality rates revealed a regression line with a slope of 0.71 (SE: 0.07). The correlation coefficient of the standardized mortality rates from the 2 models was 0.82. CONCLUSIONS: Compared with a validated model derived from clinical data, an HF mortality model derived from administrative data showed highly correlated risk-standardized mortality rate estimates, suggesting it could be used to identify high- and low-performing hospitals for HF care.

Validation and Comparison of Seven Mortality Prediction Models for Hospitalized Patients With Acute Decompensated Heart Failure.

BACKGROUND: Heart failure (HF) inpatient mortality prediction models can help clinicians make treatment decisions and researchers conduct observational studies; however, published models have not been validated in external populations. METHODS AND RESULTS: We compared the performance of 7 models that predict inpatient mortality in patients hospitalized with acute decompensated heart failure: 4 HF-specific mortality prediction models developed from 3 clinical databases (ADHERE [Acute Decompensated Heart Failure National Registry], EFFECT study [Enhanced Feedback for Effective Cardiac Treatment], and GWTG-HF registry [Get With the Guidelines-Heart Failure]); 2 administrative HF mortality prediction models (Premier, Premier+); and a model that uses clinical data but is not specific for HF (Laboratory-Based Acute Physiology Score [LAPS2]). Using a multihospital, electronic health record-derived data set (HealthFacts [Cerner Corp], 2010-2012), we identified patients ≥18 years admitted with HF. Of 13 163 eligible patients, median age was 74 years; half were women; and 27% were black. In-hospital mortality was 4.3%. Model-predicted mortality ranges varied: Premier+ (0.8%-23.1%), LAPS2 (0.7%-19.0%), ADHERE (1.2%-17.4%), EFFECT (1.0%-12.8%), GWTG-Eapen (1.2%-13.8%), and GWTG-Peterson (1.1%-12.8%). The LAPS2 and Premier models outperformed the clinical models (C statistics: LAPS2 0.80 [95% confidence interval 0.78-0.82], Premier models 0.81 [95% confidence interval 0.79-0.83] and 0.76 [95% confidence interval 0.74-0.78], and clinical models 0.68 to 0.70). CONCLUSIONS: Four clinically derived, inpatient, HF mortality models exhibited similar performance, with C statistics near 0.70. Three other models, 1 developed in electronic health record data and 2 developed in administrative data, also were predictive, with C statistics from 0.76 to 0.80. Because every model performed acceptably, the decision to use a given model should depend on practical concerns and intended use.

The association between skilled nursing facility care quality and 30-day readmission rates after hospitalization for heart failure.

The objective of the study was to assess the association between care quality of skilled nursing facilities (SNFs) and 30-day risk-adjusted readmission rate (RAR) for patients with acute decompensated heart failure (ADHF). A retrospective cohort study was conducted involving 603 discharges from a tertiary care hospital to 17 SNFs after hospitalization for ADHF. SNF quality was assessed based on the CMS 5-star quality rating and a survey of SNF characteristics and processes of care. In all, 20% of cases were readmitted within 30-days; 9.4% were for ADHF. The all-cause RARs for higher- and lower-quality SNFs were 18% (95% confidence interval [CI]=14%-23%) and 22% (95% CI=17%-26%), respectively, and the ADHF RARs were 8.8% (95% CI=6.0%-11.6%) and 10.2% (95% CI=7.0%-12.9%), respectively. There were no significant associations between ADHF RARs and individual processes of care or structural characteristics. Quality ratings of SNF or processes of care did not correlate with RAR.

Patient recruitment to a randomized clinical trial of behavioral therapy for chronic heart failure.

BACKGROUND: Patient recruitment is one of the most difficult aspects of clinical trials, especially for research involving elderly subjects. In this paper, we describe our experience with patient recruitment for the behavioral intervention randomized trial, "The relaxation response intervention for chronic heart failure (RRCHF)." Particularly, we identify factors that, according to patient reports, motivated study participation. METHODS: The RRCHF was a three-armed, randomized controlled trial designed to evaluate the efficacy and cost of a 15-week relaxation response intervention on veterans with chronic heart failure. Patients from the Veterans Affairs (VA) Boston Healthcare System in the United States were recruited in the clinic and by telephone. Patients' reasons for rejecting the study participation were recorded during the screening. A qualitative sub-study in the trial consisted of telephone interviews of participating patients about their experiences in the study. The qualitative study included the first 57 patients who completed the intervention and/or the first follow-up outcome measures. Factors that distinguished patients who consented from those who refused study participation were identified using a t-test or a chi-square test. The reason for study participation was abstracted from the qualitative interview. RESULTS: We successfully consented 134 patients, slightly more than our target number, in 27 months. Ninety-five of the consented patients enrolled in the study. The enrollment rate among the patients approached was 18% through clinic and 6% through telephone recruitment. The most commonly cited reason for declining study participation given by patients recruited in the clinic was 'Lives Too Far Away'; for patients recruited by telephone it was 'Not Interested in the Study'. One factor that significantly distinguished patients who consented from patients who declined was the distance between their residence and the study site (t-test: p <.001). The most frequently reported reason for study participation was some benefit to the patient him/herself. Other reasons included helping others, being grateful to the VA, positive comments by trusted professionals, certain characteristics of the recruiter, and monetary compensation. CONCLUSIONS: The enrollment rate was low primarily because of travel considerations, but we were able to identify and highlight valuable information for planning recruitment for future similar studies.

Thoracic massage permits use of echocardiography in unanesthetized rats.

PURPOSE: The objective of the study reported here was to investigate whether massage-like stroking of the thorax and cranial portion of the abdomen might relax unanesthetized rats sufficiently to permit in vivo echocardiography. METHODS: Nine-month-old spontaneously hypertensive rats (SHR) were first conditioned to being held by hand for 10 to 15 min twice a day for seven to 10 days. During each session, the animal was placed in supine position, and the thorax and cranial abdominal area were gently stroked (approx. 5 cm/s, 12 to 14 times/min). After the conditioning period, echocardiography was initiated. We obtained serial transthoracic two-dimensional (2-D) and M-mode echocardiograms from nine-month-old SHR that were treated with isoproterenol (60 mg/kg of body weight, s.c., x 1, followed by 30 mg/kg/d x3), and from old (20 to 24 months old) SHR, studied when labored breathing, suggestive of heart failure, was evident (SHR-F). Measurements included end-diastolic volume (EDV) and end-systolic volume (ESV). RESULTS: In the isoproterenol-treated SHR, mean +/- SD echocardiographically derived EDV (2-D, 0.29 +/- 0.05; M-mode, 0.28 +/- 0.01 ml) was not significantly different from volume at necropsy (0.33 +/- 0.04 ml). Measurements of EDV and ESV by use of M-mode and 2-D echocardiography were significantly correlated (EDV R2 = 0.48, P = 0.05; ESV R2 = 0.39, P = 0.02). Echocardiography revealed pleuropericardial effusions (4/6), atrial thrombi (5/6), and left and right ventricular enlargement (6/6). The EDV and ESV were increased fivefold (P < 0.01) and threefold (P < 0.05), respectively, versus values for SHR not in heart failure (SHR-NF). Left ventricular ejection fraction of hearts from SHR-F was markedly decreased, compared with that in SHR-NF (44 +/- 7 versus 74 +/- 2%, respectively; P < 0.05). The presence or absence of left atrial thrombi and fluid in the thoracic cavity was confirmed at necropsy in SHR-F and SHR-NF. CONCLUSION: Thoracic massage permits use of echocardiography in unanesthetized rats, thereby providing a simple, non-invasive technique for assessment of cardiac structure and function in rats without the potentially adverse effects of anesthesia.

Rolofylline: a selective adenosine 1 receptor antagonist for the treatment of heart failure.

BACKGROUND: Co-existent cardiac and renal dysfunction is increasingly recognized as both a predictor and mediator of poor outcomes in patients with advanced heart failure. Novel therapies, including adenosine receptor antagonists, are currently under development for the treatment of 'cardiorenal syndrome'. OBJECTIVES: To review the pathophysiologic rationale for using rolofylline, a selective adenosine 1 receptor antagonist, in patients with cardiorenal syndrome; and to provide a critical overview of safety and efficacy data from clinical studies. METHODS: We reviewed published data on the pharmacology of rolofylline, and used this to inform a comprehensive summary of preclinical and clinical trials. Cardiac and renal effects, and safety data with a particular reference to seizures, are highlighted. RESULTS/CONCLUSION: Rolofylline facilitates diuresis and preserves renal function in patients with acute decompensated heart failure and renal dysfunction. Pilot data also suggest beneficial effects on symptoms and short-term outcomes. The risk of seizures may be minimized by excluding high-risk patients.

A relaxation response randomized trial on patients with chronic heart failure.

PURPOSE: Patients with various medical conditions benefit from eliciting the relaxation response (RR), using a variety of techniques, but few studies have focused on chronic heart failure (CHF). We evaluated the efficacy of an RR intervention program on the quality of life (QOL) and exercise capacity of CHF patients by conducting a single-blind, 3-arm, randomized, controlled trial. METHODS: Between April 2000 and June 2002, we enrolled 95 patients with moderate severity CHF from the Veterans Affairs Boston Healthcare System. Patients in the study intervention group attended a weekly RR group for 15 weeks and were requested to practice the techniques at home twice a day. A 15-week cardiac education (EDU) program was used as an alternative intervention, and usual care (UC) was the control group. The QOL questionnaires and a bicycle test were administered at baseline and after intervention or 15 to 19 weeks. RESULTS: Eighty-three (87%) of the 95 enrolled patients completed both baseline and post-intervention QOL measures (31 RR, 24 EDU, and 28 UC). No dropout bias was observed. The RR group had significantly better QOL change scores in peace-spiritual scales than did the UC group (P = .02), adjusting for baseline scores, time between assessments, age, education, diet, and medication, whereas no significant difference was observed between the EDU and UC groups. A similar trend was observed in emotional QOL (RR and UC group comparison, P = .07). No statistically significant intervention effect on physical QOL or exercise capacity was observed. CONCLUSIONS: A short RR intervention can improve some aspects of QOL in CHF patients.