Rationale and design of the AdaptResponse trial: a prospective randomized study of cardiac resynchronization therapy with preferential adaptive left ventricular‐only pacing

The AdaptResponse trial is designed to test the hypothesis that preferential adaptive left ventricular‐only pacing with the AdaptivCRT^® algorithm reduces the incidence of the combined endpoint of all‐cause mortality and intervention for heart failure (HF) decompensation, compared with conventional cardiac resynchronization therapy (CRT), among patients with a CRT indication, left bundle branch block (LBBB) and normal atrioventricular (AV) conduction. The AdaptResponse study is a prospective, randomized, controlled, single‐blinded, multicentre, clinical trial ( ClinicalTrials.gov Identifier: NCT02205359), conducted at up to 200 centres worldwide. Following enrolment and baseline assessment, eligible subjects will be implanted with a CRT system containing the AdaptivCRT algorithm, and randomized in a 1:1 fashion to either a treatment (‘AdaptivCRT’) or control (‘Conventional CRT’) group. The study is designed to observe a primary endpoint in 1100 patients (‘event‐driven’) and approximately 3000 patients will be randomized. The primary endpoint is the composite of all‐cause mortality and intervention for HF decompensation; secondary endpoints include all‐cause mortality, intervention for HF decompensation, clinical composite score (CCS) at 6 months, atrial fibrillation, quality of life measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ), health outcome measured by the EQ‐5D instrument, all‐cause readmission after a HF admission, and cost‐effectiveness. The AdaptResponse clinical trial is powered to assess clinical endpoints and is expected to provide definitive evidence on the incremental utility of AdaptivCRT‐enhanced CRT systems.     

Beyond the cardiorenal anaemia syndrome: recognizing the role of iron deficiency

Growing awareness that heart failure, renal impairment, and anaemia are frequent co‐morbidities which can exacerbate one another in a vicious circle of clinical deterioration has led to the concept of the cardiorenal anaemia syndrome (CRAS). The role of iron deficiency within this complex interplay has been less well examined. Scrutiny of data from the recent FAIR‐HF trial raises a new hypothesis: is it time for ‘CRAS’ to be supplemented with new acronyms such as CRIDS (cardiorenal–iron deficiency syndrome) or even CRAIDS (cardiorenal–anaemia–iron deficiency syndrome)? Iron deficiency occurs frequently in heart failure patients with or without anaemia. It not only impairs oxygen transport through reduced erythropoiesis, but adversely affects oxidative metabolism, cellular energetics, and immune mechanisms, and the synthesis and degradation of complex molecules such as DNA. One large observational study in patients with heart failure found iron deficiency to be an independent predictor of death or urgent heart transplantation (hazard ratio 1.58, 95% confidence interval 1.14–2.17, P = 0.005). In the FAIR‐HF trial, i.v. iron therapy was associated with significant improvements in physical functioning in iron‐deficient patients with heart failure, even in non‐anaemic patients in whom haemoglobin levels did not change following i.v. iron administration. Key questions regarding the use of i.v. iron supplementation in the setting of heart failure merit exploration and could readily be answered by appropriately designed clinical trials. It is to be hoped that these important clinical trials are conducted, to permit a more subtle characterization of the patient's pathological condition and interventional requirements.     

Automated Office Blood Pressure is Associated with Urine Albumin Excretion in Hypertensive Subjects

BackgroundWe aimed to investigate the association between automated office blood pressure (AOBP) readings and urine albumin excretion (UAE), and to assess if this association is as close as that between 24-h ambulatory blood pressure (ABP) and UAE. A strong association would suggest that AOBP may serve as an indicator of early renal impairment.MethodsIn a sample of 162 hypertensives, we compared AOBP with ABP measurements and their associations with UAE in two consecutive 24-h urine collections measured by an immunoturbidimetric assay. Microalbuminuria was defined as UAE of 30-300 mg/24 h.ResultsThe age of the subjects was 53 ± 13 (mean ± s.d.) years. Twenty-two were microalbuminuric. In those, AOBP and 24-h ABP were higher than in the normoalbuminuric subjects: 152 ± 19 and 147 ± 20 vs. 138 ± 15 and 130 ± 11 mm Hg for systolic blood pressure (SBP), and 97 ± 15 and 92 ± 14 vs. 86 ± 10 and 82 ± 8 mm Hg for diastolic blood pressure (DBP) (P < 0.001). Correlations between AOBP and 24-h ABP with log-transformed urine albumin were 0.30 (P < 0.001) and 0.43 (P < 0.001) for SBP and 0.27 (P < 0.001) and 0.33 (P < 0.001) for DBP. Adjusting for age, sex, body mass index, and estimated glomerular filtration rate, both AOBP and 24-h ABP were independently associated with urine albumin (P < 0.001 for both associations). Receiver operating characteristics curve analysis showed a similar predictive ability for microalbuminuria for AOBP and for 24-h ABP (area under the curve: 0.819 (P < 0.001) for SBP, 0.836 (P < 0.001) for DBP vs. 0.830 (P < 0.001) for SBP and 0.845 (P < 0.001) for DBP).ConclusionsIn this study, microalbuminuria correlated similarly with high-quality AOBP and ABP readings, further supporting the use of AOBP in the clinical setting.American Journal of Hypertension 2012; doi:10.1038/ajh.2012.76.     

Effect of Atrial Pressure Increase on Effective Refractory Period and Vulnerability to Atrial Fibrillation in Patients with Lone Atrial Fibrillation

Background: There is evidence suggesting that atrial fibrillation (AF) may be induced by acute increase of atrial pressure. The aim of the present study was to investigate the effect of alterations in atrial pressure, induced by varying the atrioventricular (AV) interval, on atrial refractoriness, and on the frequency of induction of (AF), in patients with a history of lone atrial fibrillation (LAF).Methods and Results: Twenty-five patients were included in this study. The patients were divided in two groups: the LAF group, and the control group. None of the patients in either group had organic heart disease. Effective refractory period (ERP) and duration of atrial extrastimulus electrogram (A₂) were measured at two right atrial sites (high lateral wall, atrial appendage) during AV pacing (cycle length: 500 msec) with different AV intervals. Peak, minimal and mean atrial pressure increased from 8.57 ± 2.37 to 18.14 ± 4.74 mm Hg, 2 ± 2.23 to 5.14 ± 2.60 mm Hg (p = 0.0001) and from 4.28 ± 1.6 mm Hg to 9.77 ± 2.9 mm Hg (p = 0.001), respectively during AV interval modification. During lateral and atrial appendage pacing, with a progressive decrease of AV interval to 160, 100, 80, 40, 0 msec, the ERP, the dispersion of ERP, functional refractory period (FRP), A2 and latency period (LP) did not change significantly, in both groups. The frequency of induction of AF was not statistically different in both lateral atrial wall and appendage, during pacing in different AV intervals.Conclusions: This study demonstrates that alterations in the intraatrial pressure does not have important effects on atrial refractoriness and does not increase vulnerability to AF in patients with a history of LAF.     

Ocular photodynamic therapy for serous macular detachment in the diffuse retinal pigment epitheliopathy variant of idiopathic central serous chorioretinopathy

PURPOSE: To describe the anatomical and functional outcome of verteporfin ocular photodynamic therapy (PDT) in serous retinal detachment caused by the diffuse retinal pigment epitheliopathy form of chronic idiopathic central serous chorioretinopathy. DESIGN: Interventional case report. METHOD: A 48-year-old Caucasian man with unilateral exudative retinal detachment from diffuse retinal pigment epitheliopathy and visual acuity of 20/40 was managed with verteporfin PDT applied sequentially in three separate spots targeting all retinal pigment epithelium leaks identified with intravenous fluorescein angiography (IVFA). Outcome measures included visual acuity, biomicroscopic appearance, and leakage on IVFA.Clinical practice.Subretinal fluid resolved within 2 weeks; visual acuity returned to 20/20 with no recurrence at 6 months of follow-up. There was no leakage on IVFA posttreatment and no obvious toxicity.To our knowledge, this is the first report of PDT causing resolution of macular detachment in diffuse retinal pigment epitheliopathy. Its long-term results with regard to the prognosis of the disease and the recurrence rate remain to be evaluated.     

Plasma Exchange in Patients with Toxic Epidermal Necrolysis

Abstract: We describe our experience with plasma exchange (PE) therapy in 13 patients with drug‐induced toxic epidermal necrolysis (TEN), 4 of whom had malignant disorders. Skin lesions covered 17% to 100% of total body surface area and 1 to 4 mucous membranes were involved. None of the patients was hospitalized in a burn unit. The patients underwent from 2 to 5 PE sessions (mean 3.4 ± 0.2 standard error of mean [SEM], median 3) exchanging 6.6 to 17.6 L of plasma (mean 10.1 ± 0.7 SEM, median 10). PE sessions were carried out every other day in 8 patients and daily in 5. Three patients died (23%) while the remaining 10 (77%) had a full recovery. Plasmapheresis may be an effective treatment in patients with drug‐induced TEN hospitalized outside a burn unit.     

Results from an international multicentre double-blind randomized controlled trial on the perioperative efficacy and safety of bipolar vs monopolar transurethral resection of the prostate

Study Type – Therapy (RCT) Level of Evidence 1b What’s known on the subject? and What does the study add? Short‐term efficacy is similar but B‐TURP is preferable due to a more favourable safety. a) first multicentre RCT, b) adequate quality, c) experience with a new bipolar device, d) morbidity standardize using the modified Clavien classification system.

OBJECTIVE

? To compare the perioperative efficacy and safety of bipolar (B‐) and monopolar transurethral resection of the prostate (M‐TURP) in an international multicentre double‐blind randomized controlled trial using the bipolar system AUTOCON® II 400 ESU for the first time.

PATIENTS AND METHODS

? From July 2006 to June 2009, consecutive transurethral resection of the prostate (TURP) candidates with benign prostatic obstruction were prospectively recruited in four academic urological centres, randomized 1:1 into an M‐TURP or B‐TURP arm and followed up for 6 weeks after surgery. ? A total of 295 eligible patients were enrolled. ? Of these, 279 patients received treatment (M‐TURP, n= 138; B‐TURP, n= 141) and were analysed for immediate postoperative outcomes and perioperative safety. In all, 268 patients (M‐TURP, n= 129; B‐TURP, n= 139) were analysed for efficacy, which was quantified using changes in maximum urinary flow rate, postvoid residual urine volume and International Prostate Symptom Score at 6 weeks compared with baseline. Safety was estimated using sodium and haemoglobin level changes immediately after surgery and perioperative complication occurrence graded according to the modified Clavien classification system. ? Secondary outcomes included operation‐resection time, resection rate, capsular perforation and catheterization time.

RESULTS

? No significant differences were detected between each study arm except that postoperative decreases in sodium levels favoured B‐TURP (–0.8 vs –2.5 mmol/L, for B‐TURP and M‐TURP, respectively; P= 0.003). The lowest values were 131 mmol/L (B‐TURP) and 106 mmol/L (M‐TURP). Nine patients ranged between 125 and 130 mmol/L and the values for three patients were <125 mmol/L after M‐TURP. The greatest decrease was 9 mmol/L after B‐TURP (two patients). In nine patients (M‐TURP) the decrease was between 9 and 34 mmol/L. ? These results were not translated into a significant difference in TUR‐syndrome rates (1/138: 0.7% vs 0/141: 0.0%, for M‐TURP and B‐TURP, respectively; P= 0.495).

CONCLUSIONS

? In contrast to the previous available evidence, no clinical advantage for B‐TURP was shown. Perioperative efficacy, safety and secondary outcomes were comparable between study arms. ? The potentially improved safety of B‐TURP that is attributed to the elimination of dilutional hyponatraemia risk, a risk still present with M‐TURP, did not translate into a significant clinical benefit in experienced hands.