Association of pulse rate with outcomes in heart failure with reduced ejection fraction: a retrospective cohort study.

BACKGROUND: In a real-world setting, the effect of pulse rate measured at the time of diagnosis and serially during follow-up and management, on outcomes in heart failure with reduced ejection fraction (HFrEF), has not been well-studied. Furthermore, how beta-blockade use in a real-world situation modifies this relation between pulse rate and outcomes in HFrEF is not well-known. Hence, we identified a large, national, real-world cohort of HFrEF to examine the association of pulse rate and outcomes. METHODS: Using Veterans Affairs (VA) national electronic health records we identified incident HFrEF cases between 2006 and 2012. We examined the associations of both baseline and serially measured pulse rates, with mortality and days hospitalized per year for heart failure and for any cause, using crude and multivariable Cox proportional hazards and Poisson or negative binomial models, respectively. The exposure was examined as continuous, dichotomous, and categorical. Post-hoc analyses addressed the interaction of pulse rate and beta-blocker target dose. RESULTS: We identified 51,194 incident HFrEF cases (67 ± 12 years, 98% male, 77% white. A significant positive, near linear relationship was observed for both baseline and serially measured pulse rates with all-cause mortality, all-cause hospitalization and heart failure hospitalization after adjusting for covariates including beta-blocker use. Patients who had a pulse rate ≥ 70 bpm in the past 6 months had 36% (95% CI: 31-42%), 25% (95% CI: 19-32%), and 51% (95% CI: 33-72%) increased rates of mortality, all-cause hospitalization, and heart failure hospitalization, respectively, compared to patients with pulse rates < 70 bpm. A minority of subjects (15%) were treated with guideline directed beta blockade ≥50% of recommended target dose, among whom better outcomes were seen compared to those who did not achieve target dose in patients with pulse rates both above and below 70 beats per minute. CONCLUSIONS: High pulse rate, both at the time of diagnosis and during follow-up, is strongly associated with increased risk of adverse outcomes in HFrEF patients, independent of the use of beta-blockers. In a real-world setting, the majority of HFrEF patients do not achieve target dose of beta-blockade; greater use of strategies to reduce heart rate may improve outcomes in HFrEF.

Activity Sensors to Evaluate the Effect of Sacubitril/Valsartan on Quality-of-Life in Heart Failure: rational and design of the AWAKE-HF study.

AIMS: Limited data are available regarding the ability of sacubitril/valsartan to provide clinically meaningful health-related quality of life (HRQoL) improvements among individuals with heart failure (HF). Objective measurement of physical activity and sleep using actigraphy can provide insight into daily functioning and HRQoL. METHODS AND RESULTS: We designed an 18 week, multicenter, randomized, double-blind, double-dummy, parallel-group study to objectively assess changes in function and HRQoL directly after initiating sacubitril/valsartan vs. enalapril in participants with HF in their home environments. A total of 136 outpatient, ambulatory participants with New York Heart Association Class II or III HF with reduced ejection fraction (HFrEF) will be included in the study. Patients will undergo a 2 week baseline observational phase (continuing current HF treatment); data from the second week of this phase will be the baseline value for comparison with those of subsequent periods. Patients will then enter an 8 week blinded-treatment phase (randomly assigned 1:1 to sacubitril/valsartan or enalapril), followed by an 8 week open-label extension phase (treatment with only sacubitril/valsartan). The primary efficacy endpoint is the change in mean activity counts during the most active 30 min of the participant's day between baseline and the final randomized treatment phase measurement. Secondary endpoints include the change in mean sleep activity during the randomized and open-label phases; questionnaires will also assess HRQoL measures. Rather than analysing pooled actigraphy data, the researchers are considering each participant to be acting as his or her own control. CONCLUSIONS: This will be the first study to assess the effects of sacubitril/valsartan on objective measures of sleep and activity in individuals with HFrEF within the context of their daily lives. Wearable accelerometer devices will be used to gain insight into how the medication affects physical activity and sleep.

Rationale and methods of the Prospective Study of Biomarkers, Symptom Improvement, and Ventricular Remodeling During Sacubitril/Valsartan Therapy for Heart Failure (PROVE-HF).

BACKGROUND: Sacubitril/valsartan is an angiotensin receptor-neprilysin inhibitor indicated for the treatment of patients with chronic heart failure (HF) with reduced ejection fraction; however, its mechanism of benefit remains unclear. Biomarkers that are linked to ventricular remodeling, myocardial injury, and fibrosis may provide mechanistic insight and important clinical guidance regarding sacubitril/valsartan use. METHODS: This 52-week, multicenter, open-label, single-arm study is designed to (1) correlate biomarker changes with cardiac remodeling parameters, cardiovascular outcomes, and patient-reported outcome data and (2) determine short- and long-term changes in concentrations of biomarkers related to potential mechanisms of action and effects of sacubitril/valsartan therapy. Approximately 830 patients with HF with reduced ejection fraction will be initiated and titrated on sacubitril/valsartan according to United States prescribing information. Primary efficacy end points include the changes in N-terminal pro-B-type natriuretic peptide concentrations and cardiac remodeling from baseline to 1 year. Secondary end points include changes in concentrations of N-terminal pro-B-type natriuretic peptide and remodeling to 6 months, and changes in patient-reported outcomes using the Kansas City Cardiomyopathy Questionnaire-23 from baseline to 1 year. In addition, several other relevant biomarkers will be measured. Biomarker changes relative to the number of cardiovascular events in 12 months will also be assessed as exploratory end points. CONCLUSIONS: Results from the Prospective Study of Biomarkers, Symptom Improvement, and Ventricular Remodeling During Sacubitril/Valsartan Therapy for Heart Failure (PROVE-HF) will help establish a mechanistic understanding of angiotensin receptor-neprilysin inhibitor therapeutic benefits and provide clinicians with clarity on how to interpret information on biomarkers during treatment (PROVE-HF ClinicalTrials.gov identifier: NCT02887183).

Variation in hospital resource use and cost among surgical procedures using topical absorbable hemostats.

BACKGROUND: Adjunctive hemostats are used to assist with the control of intraoperative bleeding. The most common types are flowables, gelatins, thrombins, and oxidized regenerated celluloses (ORCs). In the US, Surgicel(®) products are the only US Food and Drug Administration-approved ORCs. OBJECTIVE: To compare the outcomes of health care resource utilization (HRU) and costs associated with using ORCs compared to other adjunctive hemostats (OAHs are defined as flowables, gelatins, and topical thrombins) for surgical procedures in the US inpatient setting. PATIENTS AND METHODS: A retrospective, US-based cohort study was conducted using hospital inpatient discharges from the 2011-2012 calendar years in the Premier Healthcare Database. Patients with either an ORC or an OAH who underwent a cardiovascular procedure (valve surgery and/or coronary artery bypass graft surgery), carotid endarterectomy, cholecystectomy, or hysterectomy were included. Propensity score matching was used to create comparable groups of ORC and OAH patients. Clinical, economic, and HRU outcomes were compared. RESULTS: The propensity score matching created balanced patient cohorts for cardiovascular procedure (22,718 patients), carotid endarterectomy (10,890 patients), cholecystectomy (6,090 patients), and hysterectomy (9,348 patients). In all procedures, hemostatic agent costs were 28%-56% lower for ORCs, and mean hemostat units per discharge were 16%-41% lower for ORCs compared to OAHs. Length of stay and total procedure costs for patients treated with ORCs were lower for carotid endarterectomy patients (0.3 days and US$700) and for cholecystectomy patients (1 day and US$3,350) (all P<0.001). CONCLUSION: Costs and HRU for patients treated with ORCs were lower than or similar to patients treated with OAHs. Proper selection of the appropriate hemostatic agents has the potential to influence clinical outcomes and treatment costs.

Hemostasis during urologic surgery: fibrin sealant compared with absorbable hemostat.

In the United States, fibrin sealants have been used to achieve hemostasis for nearly two decades. Although their clinical utility was first demonstrated in cardiac surgery, their effectiveness and safety have since been demonstrated to extend to a wide array of procedures. Fibrin sealants typically contain two components-fibrinogen and thrombin-that are combined and delivered simultaneously to a target bleeding site in order to achieve hemostasis. However, many commercial formulations contain other additional components, such as antifibrinolytic agents, that have been associated with adverse outcomes. This subanalysis compares the safety and effectiveness of a fibrin sealant versus an absorbable hemostat for achieving hemostasis during urologic procedures with mild to moderate bleeding.

Reduction in hospital costs and resource consumption associated with the use of advanced topical hemostats during inpatient procedures.

OBJECTIVE: The use of hemostatic agents has increased over time for all surgical procedures. The purpose of this study was to evaluate the newer topical absorbable hemostat products Surgicel * Fibrillar † and Surgicel SNoW ‡ (Surgicel advanced products, abbreviated as SAPs) compared to the older product Surgicel Original (SO) with respect to healthcare resource use and costs in procedures where these hemostats are most commonly used. RESEARCH DESIGN AND METHODS: A retrospective analysis of the Premier hospital database was used to identify adults who underwent brain/cerebral (BC), cardiovascular (CV: valve surgery and coronary artery bypass graft) and carotid endarterectomy (CEA) between January 2011-December 2012. Among these patients, those treated with SAPs were compared to those treated with SO. Propensity score matching (PSM) was used to create comparable groups to evaluate differences between SAPs and SO. MAIN OUTCOME MEASURES: The primary end-points for this study were length of stay (LOS), all-cause total cost, number of intensive care unit (ICU) days, ICU cost, transfusion costs and units, and SO/SAP product units per discharge. RESULTS: Matched PSM created patient cohorts for SO and SAPs were created for BC (n = 758 for both groups), CV (n = 3388 for both groups), and CEA (n = 2041 for both groups) procedures. Patients that received SAPs had a 14-16% lower mean LOS for each procedure compared to SO, as well as 12-18% lower total mean cost per discharge for each procedure (p < 0.02 for all results). Mean ICU costs for SAPs were also lower, with a reduction of 20% for BC and 19% for CV compared to SO (p < 0.01). However, for CEA, there was no statistically significant difference in ICU costs for SAPs compared to SO. CONCLUSIONS: In a retrospective hospital database analysis, the use of SAPs were associated with lower healthcare resource utilization and costs compared to SO.

Hemodynamic characterization of calcified stenotic human aortic valves before and after treatment with a novel aortic valve repair system.

BACKGROUND AND AIM OF THE STUDY: The repair of calcified stenotic aortic valves may be a viable alternative to current valve treatments for early-stage aortic valve disease. To date, evaluation of valve repair feasibility on the benchtop has not been performed. A pulsatile flow system for testing intact human aortic valves was developed to perform quantitative hemodynamic and mechanical assessment of a new aortic valve repair approach. METHODS: Intact calcified human aortic valves were divided into two groups with effective orifice area (EOA) > or =2.0 cm2 (group I, n = 6) or <2.0 cm2 (group II, n = 6). All valves were chemically debrided in stages for up to 60 min. A subset of valves in each group was also surgically debrided. At each stage, pre- and post-treatment hemodynamic assessment and video motion analysis were performed in the pulsatile flow system at multiple levels of physiological loading. Mineral removed was quantified using atomic absorption spectroscopy. RESULTS: Progressive removal of mineral with both mechanical and chemical debridement was associated with improved hemodynamic function of calcified human aortic valves. Improvements in EOA of up to 40% and decreases in transvalvular pressure gradient (deltaP) of up to 46% were seen. No clinically relevant increases in regurgitation were observed. CONCLUSION: Repair of stenotic calcified aortic valves using surgical and chemical debridement showed that removal of calcific deposits was directly associated with improvements in valve hemodynamic function. The level of improvement was proportional to the degree of aortic valve stenosis, to the use of surgical debridement, and to the duration of chemical debridement treatment. The study results suggested that aortic valve repair warrants further investigation as an alternative to current valve treatments in patients with early to mid-stage calcific aortic valve disease.

The four seasons of ruptured sinus of valsalva aneurysms: case presentations and review.

The sinuses of Valsalva are 3 distinct outpouchings of the aortic wall associated with the 3 cusps of the aortic valve that may develop aneurysmal dilation because of weakness of or injury to the sinus wall. Rupture of a sinus aneurysm can create an aortocardiac fistula. Ruptured sinuses of Valsalva aneurysms (RSVAs) may present a diagnostic dilemma because of their varied clinical presentations. However, if included on a differential, they are easily diagnosed and surgically treated. In our article we detail 4 RSVA cases, each demonstrating a manner in which an RSVA may present clinically. Our first case involves a 68-year-old patient with an RSVA diagnosis after presenting with cardiac arrest and congestive heart failure. Our second case involves a 42-year-old patient with an RSVA diagnosis in the context of acute chest pain, ischemic electrocardiographic changes, and hypotension. Our third RSVA case involves a 60-year-old patient who presented solely with a sudden onset of lower-extremity edema. Our fourth case involves a 46-year-old asymptomatic patient with RSVA diagnosed during a routine physical exam. Comparisons of reported case series from around the world illustrate RSVA epidemiology, concomitant lesions, clinical presentations, and repair techniques. Comparisons of Eastern and Western series reveal that the incidence of RSVAs is higher in Eastern than in Western countries, with a 4:1 male preponderance across ethnic lines. Among the Eastern series reporting RSVAs, ventricular septal defects and aortic valve incompetence were the only frequently associated concomitant lesions. In contrast, Western series of RSVAs showed a wide range of concomitant lesions. The difficulty in diagnosing RSVAs is mainly due to the variability of their clinical impact and presentation. These factors largely depend on the cardiac chamber into which the aortocardiac fistula forms. However, once RSVA is on a differential, the advent of transesophageal and transthoracic radiography has made RSVA diagnosis relatively easy. Surgical repairs of RSVAs are of low risk and generally have an excellent long-term prognosis. As a result, many authors believe that early surgical intervention in patients with an RSVA is justified. Among the series studied, there is evidence that the patch technique is the safest approach because of its lower association with fistula recurrence. This article highlights for the clinician the diversity of clinical presentations of this often overlooked disorder.