The hidden costs of anticoagulation in hospitalized patients with non-valvular atrial fibrillation.

INTRODUCTION: Non-valvular atrial fibrillation (NVAF) and ischemic stroke are collectively associated with annual hospital costs of tens of billions of dollars in the USA. Oral anticoagulant (OAC) treatment with warfarin reduces the risk of stroke in patients with NVAF. Unfortunately, because of the complexity of warfarin therapy and potential for adverse events (AEs), many patients who might benefit go untreated or receive suboptimal therapy, increasing their stroke and/or bleeding risk. AREAS COVERED: This review explores current hospital costs and resource utilization for NVAF patients on warfarin therapy and the potential impact of newer OACs in this area. EXPERT OPINION: Many ischemic strokes could be prevented through wider use of OACs. Further, admissions due to anticoagulant-associated AEs could be reduced by optimizing OAC therapy. In the hospital, specialized anticoagulation services can decrease costs by improving the effectiveness of warfarin management, empowering patients through education and optimizing care transitions. With fewer interactions and no dose titration or monitoring required, the novel OACs (NOACs) have the potential to further decrease inpatient resource utilization and costs. It is important that, as data become available, inpatient costs are included in cost-benefit comparisons between warfarin and the NOACs.

Standard chest radiograph predicts left ventricular lead location in chronic resynchronization therapy patients more accurately than intraoperative fluoroscopy.

INTRODUCTION: Targeting the proper left ventricular lead site is important in cardiac resynchronization therapy (CRT) procedures, as suboptimal lead locations may result in a lack of clinical response. Left ventricular lead locations are typically confirmed using fluoroscopy (fluoro) with AP, RAO, and LAO orientations. However, standard fluoro may inadequately delineate true left ventricular lead locations, due to insufficient angulation or extreme cardiac rotation. Posteroanterior and lateral chest radiograph (CXRPAL), performed routinely to verify lead stability and freedom from complication, may better confirm left ventricular lead location due to utilization of a straight lateral view. HYPOTHESIS: Compared to fluoro, lead localization using CXRPAL will be more predictive of true left ventricular lead location in CRT patients. METHODS: Of 252 medically optimized CHF patients who underwent CRT implantation by multiple operators from October 2001 to August 2011, 46 (mean age, 58.9 ± 13.2 years; 10 female; 19 ICM; 19 LBBB; mean ejection fraction, 26.6 ± 8.9 %; mean QRS width, 144.4 ms) had CT scanning performed as part of routine medical care and comprise this study. Operative reports of left ventricular lead location by fluoro were reviewed. Left ventricular lead location was identified on CXRPAL by three independent observers blinded to operative results. Left ventricular lead locations according to fluoro and CXRPAL were correlated with CT scan at a mean follow-up of 57.6 ± 28.8 months (Tables 1 and 2). RESULTS: Compared to standard fluoro, CXRPAL agreed better with CT scan (κ = 0.413 fluoro vs. κ = 0.864 CXRPAL on the vertical axis, and κ = 0.086 fluoro vs. κ = 0.864 CXRPAL on the horizontal axis) for identification of left ventricular lead location. CONCLUSIONS: In this small study of 46 CRT patients, interpretation of left ventricular lead location using CXRPAL correlated better with true lead location identified on CT scan, compared to standard fluoroscopy. Use of a steep lateral view during CRT implantation may be necessary to accurately identify left ventricular lead locations.

Venous thromboembolism: annualised United States models for total, hospital-acquired and preventable costs utilising long-term attack rates.

Healthcare reform is upon the United States (US) healthcare system. Prioritisation of preventative efforts will guide necessary transitions within the US healthcare system. While annual deep-vein thrombosis (DVT) costs have recently been defined at the US national level, annual pulmonary embolism (PE) and venous thromboembolism (VTE) costs have not yet been defined. A decision tree and cost model were developed to estimate US health care costs for total PE, total hospital-acquired PE, and total hospital-acquired "preventable" PE. The previously published DVT cost model was modified, updated and combined with the PE cost model to elucidate the same three categories of costs for VTE. Direct and indirect costs were also delineated. For VTE in the base model, annual cost ranges in 2011 US dollars for total, hospital- acquired, and hospital-acquired "preventable" costs and were $13.5-$27.2, $9.0-$18.2, and $4.5-$14.2 billion, respectively. The first sensitivity analysis, with higher incidence rates and costs, demonstrated annual US total, hospital-acquired, and hospital-acquired "preventable" VTE costs ranging from $32.1-$69.3, $23.7-$51.5, and $11.9-$39.3 billion, respectively. The second sensitivity analysis with long-term attack rates (LTAR) for recurrent events and post-thrombotic syndrome and chronic pulmonary thromboembolic hypertension demonstrated annual US total, hospital-acquired, and hospital-acquired "preventable" VTE costs ranging from $15.4-$34.4, $10.3-$25.4, and $5.1-$19.1 billion, respectively. PE costs comprised a majority of the VTE costs. Prioritisation of effective VTE preventative strategies will reduce significant costs, morbidity and mortality within the US healthcare system. The cost models may be utilised to estimate other countries' costs or VTE-specific disease states.

Particle formation and risk of embolization during transseptal catheterization: comparison of standard transseptal needles and a new radiofrequency transseptal needle.

OBJECTIVE: Anecdotally, the Brockenbrough transseptal needle generates plastic particles through a process of skiving (shaving off particles), when advanced through the dilator and sheath. This study was performed to assess particle creation by the Brockenbrough needle during transseptal catheterization. We explore strategies that may reduce this phenomenon, including use of the Brockenbrough stylet and a radiofrequency transseptal needle. METHOD: In vitro simulations of transseptal catheterization were performed using Brockenbrough transseptal needles and a new radiofrequency transseptal needle. Particles that were created during advancement of transseptal needles through the sheath and dilator were collected and analyzed. Particles in the visible range of 50 µm to 4 mm were identified using a light microscope, whereas particles in the sub-visible, yet clinically relevant range of 10 to 50 µm, were counted using a light obscuration method. RESULTS: All simulated procedures using the Brockenbrough transseptal needles, with or without a stylet, generated visible particles. Simulated procedures with the radiofrequency transseptal needle generated no visible particles. A greater number of sub-visible particles were generated with the standard Brockenbrough transseptal needle (BKR-1) without stylet compared with the standard Brockenbrough needle (BRK-1) with stylet, the Brockenbrough extra sharp (BRK-1XS) needle with or without stylet, and the radiofrequency needle (NRG C1). CONCLUSION: Clinically relevant particles, both visible and sub-visible, with the potential for causing embolic complications, are generated by the BRK-1 needle without stylet. Use of a stylet in the BRK-1 needle, or the BRK-1XS needle with or without stylet, appears to reduce the size and amount of particles created. The NRG C1 needle appears to eliminate visible particles and is comparable to the BRK-1 with stylet and the BRK-1XS with or without stylet in generation of sub-visible particles. Important steps can be taken to minimize the creation of particles during the advancement of the BRK-1 through the transseptal sheath and dilator.

Assessment of metabolic phenotypes in patients with non-ischemic dilated cardiomyopathy undergoing cardiac resynchronization therapy.

Studies of myocardial metabolism have reported that contractile performance at a given myocardial oxygen consumption (MVO2) can be lower when the heart is oxidizing fatty acids rather than glucose or lactate. The objective of this study is to assess the prognostic value of myocardial metabolic phenotypes in identifying non-responders among non-ischemic dilated cardiomyopathy (NIDCM) patients undergoing cardiac resynchronization therapy (CRT). Arterial and coronary sinus plasma concentrations of oxygen, glucose, lactate, pyruvate, free fatty acids (FFA), and 22 amino acids were obtained from 19 male and 2 female patients (mean age 56 ± 16) with NIDCM undergoing CRT. Metabolite fluxes/MVO2 and extraction fractions were calculated. Flux balance analysis (FBA) was performed with MetaFluxNet 1.8 on a metabolic network of the cardiac mitochondria (189 reactions, 230 metabolites) reconstructed from mitochondrial proteomic data (615 proteins) from human heart tissue. Non-responders based on left ventricular ejection fraction (LVEF) demonstrated a greater mean FFA extraction fraction (35% ± 17%) than responders [18 ± 10%, p = 0.0098, area under the estimated ROC curve (AUC) was 0.8238, S.E. 0.1115]. Calculated adenosine triphosphate (ATP)/MVO2 using FBA correlated with change in New York Heart Association (NYHA) class (rho = 0.63, p = 0.0298; AUC = 0.8381, S.E. 0.1316). Non-responders based on both LVEF and NYHA demonstrated a greater mean FFA uptake/MVO2 (0.115 ± 0.112) than responders (0.034 ± 0.030, p = 0.0171; AUC = 0.8593, S.E. 0.0965). Myocardial FFA flux and calculated maximal ATP synthesis flux using FBA may be helpful as biomarkers in identifying non-responders among NIDCM patients undergoing CRT.

Patterns of venous reflux and obstruction in patients with skin damage due to chronic venous disease.

Identified were characteristics of individuals with skin damage related to chronic venous disease. Patients with chronic venous disease (n = 164) were evaluated with duplex ultrasound imaging and were placed in classes 4, 5, and 6 according to the CEAP classification. Their findings were compared with 100 class 2 controls. The prevalence of deep venous thrombosis was higher in the study group (23.7%) versus controls (5.1%; P < .0001), as was the prevalence of deep, perforator, and combined patterns of disease (P < .0001, P < .0007, and P < .0001). The mean duration of disease in controls 2 was shorter compared with the study group (P = .0019). The prevalence of reflux and obstruction within the study group was higher than in controls (P = .0021). Skin changes accurately reflect severity of chronic venous disease. Superficial and perforator vein reflux is the major cause of disease.

Uncommon leg ulcers in the lower extremity.

OBJECTIVE: To determine the prevalence of uncommon ulcers, unrelated to venous or arterial etiology, in patients presenting to vascular clinics. METHODS: This was a multicenter prospective study of consecutive patients presenting with lower extremity ulceration. The settings were university hospital outpatient centers and venous clinics. A total of 799 limbs in 710 patients with leg ulcers were evaluated. Patients with venous ulcer disease and with evidence of arterial disease with an ankle-brachial index less than 0.7 were excluded from the study. Out of 710 patients, 17 patients with a total of 21 limbs fit the criteria for inclusion. All limbs included in this study underwent physical examination, ankle-brachial index measurements, duplex ultrasonography, and skin biopsies. RESULTS: The mean age of patients with uncommon ulcers was 65.6 years, and the mean duration was 5.5 years. A total of 2.1% of all leg ulcers seen were due to uncommon etiology unrelated to venous or arterial pathology. Most of these ulcers were located in the medial lower calf (n = 19). In six patients with ulcers, the histology did not reveal any specific cause; five had a neoplasia, three had chronic inflammation, two had sickle cell disease, two had vasculitis, one had rheumatoid arthritis, one had pyoderma gangrenosum, and one had ulcer due to hydroxyurea. CONCLUSIONS: The prevalence of leg ulcers unrelated to arterial and venous disease that presented with signs and symptoms of chronic venous disease was 2.1%. Their etiology is variable, most often including vasculitis, neoplasia, metabolic disorders, infection, and other rare causes. Early identification of uncommon ulcers may facilitate timely and appropriate management.

Are the American College of Cardiology/Emergency Cardiac Care (ACC/ECC) guidelines useful in triaging patients to telemetry units?

PURPOSE: To determine if the ACC/ECC guidelines (1991) properly stratify patients according to risk of arrhythmia, defined as a single event on cardiac monitoring, and benefit, defined as a subsequent management change from a recorded telemetry event. SUBJECTS AND METHODS: In 2003, a prospective study of 217 consecutive patients admitted to a 24-bed telemetry unit was conducted for 25 days at a major academic hospital. Patients were categorized per ACC/ECC guidelines as appropriate (class I & II) or inappropriate (class III) based on a non-cardiologist admission diagnosis. A cardiologist-led group then reclassified patients at the time of admission using a brief interview. Continuous telemetry-recorded arrhythmias and resultant management changes were reviewed and recorded daily. Subgroup analysis of patients admitted with a chief complaint of chest pain was also performed. In 2004, after this trial was performed, the American Heart Association released a scientific statement updating practice standards for ECG monitor; however, this paper is based upon the original 1991 ACC/ECC guidelines. RESULTS: Reclassification significantly decreased the percentage of all class I & II patients from 91% to 71% (P<0.001) and the percentage of class I & II patients with chest pain from 100% to 58% (P<0.001) without increasing the percentage of arrhythmias occurring in class III patients. Class II patients had a statistically significant higher percentage of arrhythmias than class I and III patients before and after reclassification (P<0.001 and P<0.001, respectively). Management changes occurring as a direct result of telemetry events were higher in class II than class I or III patients before and after reclassification (P = 0.01 and P = 0.03). Life-threatening arrhythmias (sustained ventricular tachycardia or ventricular fibrillation) occurred in 1% of the 216 patients enrolled in this study. CONCLUSIONS: (1) Cardiology input using ACC/ECC guidelines and a brief interview at admission safely reduced total admissions primarily by identifying low risk chest pain admissions inappropriate for inpatient telemetry monitoring. (2) Life threatening arrhythmias occurring in patients admitted to telemetry are rare.

Renal dialysis as a risk factor for appropriate therapies and mortality in implantable cardioverter-defibrillator recipients.

BACKGROUND: Patients with end-stage renal disease are at increased risk for sudden cardiac death, although the utility of implantable cardioverter-defibrillators (ICDs) in these patients is unknown. OBJECTIVES: The purpose of this study was to evaluate whether end-stage renal disease is an independent risk factor for appropriate ICD therapy for ventricular tachycardia (VT) or ventricular fibrillation (VF) and to compare the long-term survival of ICD recipients with and without end-stage renal disease. METHODS: A retrospective cohort study was performed on ICD recipients at a single center. The primary endpoint was first appropriate ICD therapy for VT/VF. The secondary endpoint was survival. RESULTS: The study included 585 patients, 19 (3.2%) of whom had end-stage renal disease prior to device implantation. Average follow-up time was 2.2 +/- 2.4 years, during which time 156 patients (26.7%) received appropriate ICD therapy. End-stage renal disease was strongly associated with appropriate ICD therapy (hazard ratio 2.30, 95% confidence interval 1.17-4.54) and remained a significant predictor following adjustment for implant indication, ejection fraction, diabetes, hypertension, and beta-blocker use. Survival was significantly shorter in the end-stage renal disease patients, with a median survival time of 3.2 +/- 0.6 (SEM) years in the dialysis cohort and 7.4 +/- 0.5 (SEM) years in those without end-stage renal disease (log rank P = .009). The majority of deaths in the end-stage renal disease cohort were due to non-device-related infection. CONCLUSION: In this cohort, end-stage renal disease was the single greatest predictor of ICD therapies for VT/VF. The survival rate was significantly shorter than that of ICD recipients without end-stage renal disease, suggesting that comorbidities in end-stage renal disease patients meeting current implant indications may reduce the survival benefit of ICD placement in this population.

Definition of venous reflux in lower-extremity veins.

PURPOSE: This prospective study was designed to determine the upper limits of normal for duration and maximum velocity of retrograde flow (RF) in lower extremity veins. METHODS: Eighty limbs in 40 healthy subjects and 60 limbs in 45 patients with chronic venous disease were examined with duplex scanning in the standing and supine positions. Each limb was assessed for reflux at 16 venous sites, including the common femoral, deep femoral, and proximal and distal femoral veins; proximal and distal popliteal veins; gastrocnemial vein; anterior and posterior tibial veins; peroneal vein; greater saphenous vein, at the saphenofemoral junction, thigh, upper calf, and lower calf; and lesser saphenous vein, at the saphenopopliteal junction and mid-calf. Perforator veins along the course of these veins were also assessed. In the healthy volunteers, 1553 vein segments were assessed, including 480 superficial vein segments, 800 deep vein segments, and 273 perforator vein segments; and in the patients, 1272 vein segments were assessed, including 360 superficial vein segments, 600 deep vein segments, and 312 perforator vein segments. Detection and measurement of reflux were performed at duplex scanning. Standard pneumatic cuff compression pressure was used to elicit reflux. Duration of RF and peak vein velocity were measured immediately after release of compression. RESULTS: Duration of RF in the superficial veins ranged from 0 to 2400 ms (mean, 210 ms), and was less than 500 ms in 96.7% of these veins. In the perforator veins, regardless of location, outward flow ranged from 0 to 760 ms (mean, 170 ms), and was less than 350 ms in 97% of these veins. In the deep veins, RF ranged from 0 to 2600 ms. Mean RF in the deep femoral veins and calf veins was 190 ms, and was less than 500 ms in 97.6% of these veins. In the femoropopliteal veins, mean RF was 390 ms, and ranged from 510 to 2600 ms in 21 of 400 segments; however, RF was less than 990 ms in 99% of these veins. Duration of RF was significantly longer in all three veins systems in patients (P <.0001 for all comparisons). With a cutoff value of more than 1000 ms rather than more than 500 ms, prevalence of abnormal RF in the femoropopliteal veins was significantly reduced, from 29% to 18% (P =.002). Thirty-seven vein segments (2.4%) had RF greater than 500 ms in the supine position, compared with less than 500 ms in 22 of these vein segments (59%) in the standing position. Of the 48 vein segments (3.1%) with RF greater than 500 ms in the standing position, RF was less than 500 ms in 6 of these vein segments (13%) in the supine position. Similar observations were noted in patient veins. There was no association between RF and peak vein velocity. Peak vein velocity had no significance in determining reflux. CONCLUSIONS: The cutoff value for reflux in the superficial and deep calf veins is greater than 500 ms. However, the reflux cutoff value for the femoropopliteal veins should be greater than 1000 ms. Outward flow in the perforating veins should be considered abnormal at greater than 350 ms. Reflux testing should be performed with the patient standing.