Miniaturized implantable cardiac monitor with a long sensing vector (BIOMONITOR III): Insertion procedure assessment, sensing performance, and home monitoring transmission success.

BACKGROUND: Implantable Cardiac Monitors (ICMs) are used for long-term monitoring of arrhythmias. BIOMONITOR III is a novel ICM with a miniaturized profile, long sensing vector due to a flexible antenna, simplified implantation with a dedicated insertion tool for pocket formation and ICM placement in a single step, and daily automatic Home Monitoring (HM) function. METHODS: In 47 patients undergoing BIOMONITOR III insertion for any ICM indication, 16 investigators at 10 Australian sites assessed handling characteristics of the insertion tool, R-wave amplitudes, noise burden, P-wave visibility, and HM transmission success. Patients were followed for 1 month. RESULTS: All 47 attempted insertions were successful. Median time from skin incision to removal of the insertion tool after ICM insertion was 39 s (IQR 19-65) and to wound closure and cleaning was 4.7 min (IQR 3.5-7.8). All aspects of the insertion tool were rated as "good" or "excellent" in ≥97.9% and "fair" in ≤2.1% of patients, except for "force needed for tunnelling" (91.5% good/excellent, 8.5% fair). Based on HM data, R-waves in the first month were stable at 0.70 ± 0.37 mV. Median noise burden (disabling automatic rhythm evaluation) was 0.19% (IQR 0.00-0.93), equivalent to 2.7 min (IQR 0.0-13.4) per day. In HM-transmitted ECG strips with regular sinus rhythm, P-waves were visible in 89 ± 24% of heart cycles. Patient-individual automatic Home Monitoring transmission success was 98.0% ± 5.5%. CONCLUSIONS: The novel ICM performed well in all aspects studied, including fast insertion, reliable R-wave sensing, good P-wave visibility, and highly successful HM transmissions.

Effect of fenofibrate on amputation events in people with type 2 diabetes mellitus (FIELD study): a prespecified analysis of a randomised controlled trial.

BACKGROUND: Amputations in people with type 2 diabetes mellitus substantially impair their quality of life and impose high costs on health-care systems. Our aim was to assess the effect of fenofibrate on amputation events in a large cohort of patients with type 2 diabetes. METHODS: In the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, 9795 patients aged 50-75 years with type 2 diabetes were randomly assigned by computer-generated randomisation sequence to receive fenofibrate 200 mg per day (n=4895) or matching placebo (n=4900) for 5 years' duration. Information about non-traumatic amputation-a prespecified tertiary endpoint of the study-was routinely gathered. Clinicians who were masked to treatment allocation adjudicated amputations as minor or major (below or above the ankle, respectively). Amputations were also classified on the basis of whether or not large-vessel disease was present in the limb, to distinguish those related to large-artery atherosclerosis from those predominantly related to microvascular disease. Analysis was by intention to treat (ITT). The FIELD study is registered as an International Standard Randomised Controlled Trial, number ISRCTN64783481. FINDINGS: All 9795 patients were included in the ITT population. 115 patients had one or more non-traumatic lower-limb amputations due to diabetes. Previous cardiovascular disease, microvascular disease, previous non-traumatic amputation or skin ulcer, smoking, and longer duration of diabetes were more frequent in patients who had amputations during the trial than in those who had other cardiovascular events or in those who had neither event (all p<0.001 for three-way comparison). Mean lipid concentrations differed between patients who had on-study amputations and those who had other cardiovascular events or neither event, but by no more than 0.2 mmol/L. The risks of first amputation (45 vs 70 events; hazard ratio [HR] 0.64, 95% CI 0.44-0.94; p=0.02) and minor amputation events without known large-vessel disease (18 vs 34 events; 0.53, 0.30-0.94; p=0.027) were lower for patients assigned to fenofibrate than for patients assigned to placebo, with no difference between groups in risk of major amputations (24 vs 26 events; 0.93, 0.53-1.62; p=0.79). INTERPRETATION: Classic markers of macrovascular and microvascular risk were associated with lower extremity amputations in patients with type 2 diabetes. Treatment with fenofibrate was associated with a lower risk of amputations, particularly minor amputations without known large-vessel disease, probably through non-lipid mechanisms. These findings could lead to a change in standard treatment for the prevention of diabetes-related lower-limb amputations. FUNDING: Laboratoires Fournier SA (now part of Solvay Pharmaceuticals) and National Health and Medical Research Council of Australia.

Fenofibrate Rescues Diabetes-Related Impairment of Ischemia-Mediated Angiogenesis by PPARα-Independent Modulation of Thioredoxin-Interacting Protein.

Fenofibrate, a peroxisome proliferator-activated receptor α (PPARα) agonist, reduces lower limb amputations in patients with type 2 diabetes. The mechanism is, however, unknown. In this study, we demonstrate that fenofibrate markedly attenuates diabetes-related impairment of ischemia-mediated angiogenesis. In a murine model of hindlimb ischemia, daily oral fenofibrate treatment restored diabetes-impaired blood flow recovery, foot movement, hindlimb capillary density, vessel diameter, and vascular endothelial growth factor signaling to nondiabetic levels in both wild-type and PPARα-knockout mice, indicating that these fenofibrate effects are largely PPARα independent. In vitro, fenofibric acid (FFA) rescued high glucose-induced (25 mmol/L) impairment of endothelial cell migration, tubulogenesis, and survival in a PPARα-independent manner. Interestingly, fenofibrate in vivo and FFA in vitro reversed high glucose-induced expression of thioredoxin-interacting protein (TXNIP), an exquisitely glucose-inducible gene previously identified as a critical mediator of diabetes-related impairment in neovascularization. Conversely, adenoviral overexpression of TXNIP abrogated the restorative effects of FFA on high glucose-impaired endothelial cell function in vitro, indicating that the effects of FFA are mediated by TXNIP. We conclude that fenofibrate rescues diabetic impairment in ischemia-mediated angiogenesis, in large part, by PPARα-independent regulation of TXNIP. These findings may therefore explain the reduction in amputations seen in patients with diabetes treated with fenofibrate.

Shock avoidance and the newer tachycardia therapy algorithms.

Sudden cardiac death is a leading cause of death in the United States and Europe. Implantable cardioverter defibrillators (ICDs) are a cornerstone of therapy for patients at risk of first occurrence of ventricular arrhythmia, or secondary prevention in those who have previously suffered cardiac arrest or life-threatening arrhythmias. Despite their efficacy, ICD shocks are associated with significant physical and psychological adverse effects. As technology has progressed, newer device programing methods have allowed for arrhythmia suppression and termination without the need for high-energy defibrillation, thus improving patient satisfaction, health, and outcomes.

Benefits and safety of long-term fenofibrate therapy in people with type 2 diabetes and renal impairment: the FIELD Study.

OBJECTIVE: Diabetic patients with moderate renal impairment (estimated glomerular filtration rate [eGFR] 30-59 mL/min/1.73 m(2)) are at particular cardiovascular risk. Fenofibrate's safety in these patients is an issue because it may elevate plasma creatinine. Furthermore, guidelines regarding fenofibrate dosing in renal impairment vary internationally. We investigated fenofibrate's effects on cardiovascular and end-stage renal disease (ESRD) events, according to eGFR, in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study. RESEARCH DESIGN AND METHODS: Type 2 diabetic patients (aged 50-75 years) with eGFR ≥30 mL/min/1.73 m(2) were randomly allocated to a fixed dose of fenofibrate (200 mg daily) (n = 4,895) or placebo (n = 4,900) for 5 years. Baseline renal function (Modification of Diet in Renal Disease equation) was grouped by eGFR (30-59, 60-89, and ≥90 mL/min/1.73 m(2)). The prespecified outcome was total cardiovascular events (composite of cardiovascular death, myocardial infarction, stroke, and coronary/carotid revascularization). Serious adverse events and instances of ESRD (plasma creatinine >400 µmol/L, dialysis, renal transplant, or renal death) were recorded. Analysis was by intention to treat. RESULTS: Overall, fenofibrate reduced total cardiovascular events, compared with placebo (hazard ratio 0.89 [95% CI 0.80-0.99]; P = 0.035). This benefit was not statistically different across eGFR groupings (P = 0.2 for interaction) (eGFR 30-59 mL/min/1.73 m(2): 0.68 [0.47-0.97], P = 0.035; eGFR ≥90 mL/min/1.73 m(2): 0.85 [0.70-1.02], P = 0.08). ESRD rates were similar between treatment arms, without adverse safety signals of fenofibrate use in renal impairment. CONCLUSIONS: Patients with type 2 diabetes and moderate renal impairment benefit from long-term fenofibrate, without excess drug-related safety concerns compared with those with no or mild renal impairment. Fenofibrate treatment should not be contraindicated in moderate renal impairment, suggesting that current guidelines may be too restrictive.