Multicenter Randomized Controlled Crossover Trial Comparing Hemodynamic Optimization Against Echocardiographic Optimization of AV and VV Delay of Cardiac Resynchronization Therapy: The BRAVO Trial.

OBJECTIVES: BRAVO (British Randomized Controlled Trial of AV and VV Optimization) is a multicenter, randomized, crossover, noninferiority trial comparing echocardiographic optimization of atrioventricular (AV) and interventricular delay with a noninvasive blood pressure method. BACKGROUND: Cardiac resynchronization therapy including AV delay optimization confers clinical benefit, but the optimization requires time and expertise to perform. METHODS: This study randomized patients to echocardiographic optimization or hemodynamic optimization using multiple-replicate beat-by-beat noninvasive blood pressure at baseline; after 6 months, participants were crossed over to the other optimization arm of the trial. The primary outcome was exercise capacity, quantified as peak exercise oxygen uptake. Secondary outcome measures were echocardiographic left ventricular (LV) remodeling, quality-of-life scores, and N-terminal pro-B-type natriuretic peptide. RESULTS: A total of 401 patients were enrolled, the median age was 69 years, 78% of patients were men, and the New York Heart Association functional class was II in 84% and III in 16%. The primary endpoint, peak oxygen uptake, met the criterion for noninferiority (pnoninferiority = 0.0001), with no significant difference between the hemodynamically optimized arm and echocardiographically optimized arm of the trial (mean difference 0.1 ml/kg/min). Secondary endpoints for noninferiority were also met for symptoms (mean difference in Minnesota score 1; pnoninferiority = 0.002) and hormonal changes (mean change in N-terminal pro-B-type natriuretic peptide -10 pg/ml; pnoninferiority = 0.002). There was no significant difference in LV size (mean change in LV systolic dimension 1 mm; pnoninferiority < 0.001; LV diastolic dimension 0 mm; pnoninferiority <0.001). In 30% of patients the AV delay identified as optimal was more than 20 ms from the nominal setting of 120 ms. CONCLUSIONS: Optimization of cardiac resynchronization therapy devices by using noninvasive blood pressure is noninferior to echocardiographic optimization. Therefore, noninvasive hemodynamic optimization is an acceptable alternative that has the potential to be automated and thus more easily implemented. (British Randomized Controlled Trial of AV and VV Optimization [BRAVO]; NCT01258829).

Registry report of structural and functional cardiac abnormalities diagnosed by echocardiography in an asymptomatic population.

BACKGROUND: The epidemiology of heart disease is changing, with rheumatic heart disease becoming less common but degenerative valve disorders, heart failure and atrial fibrillation (AF) increasing. OBJECTIVE: We sought to determine the prevalence of structural cardiac abnormalities in the apparently symptom-free adult population within our prospective echocardiography (echo) registry. METHODS: Our echo registry comprised echo studies and associated demographic and clinical data obtained prospectively from 362 consecutive asymptomatic subjects aged 50-74 years and without known heart disease referred between 2011 and 2012 from general practices in the South East of England. RESULTS: 221 echo abnormalities were detected in 178 (49%) subjects (46% men; mean (±SD) age 63.9±9.2 years; 98% Caucasian). A major abnormality was detected in seven subjects: four had a large secundum atrial septal defect, one had critical aortic stenosis, one severe mitral regurgitation and one features of hypertrophic cardiomyopathy. Twelve subjects had left ventricular systolic dysfunction with an ejection fraction (EF) <50% (of whom 10 had EF <40%). Four subjects had AF. Minor echo abnormalities were evident in the remaining 171 (47%) subjects. Abnormalities were commoner in patients with cardiovascular risk factors or a history of cardiac disease than in those without (53% vs 38%). In multivariate analyses stratified by gender, for women, increased age (F=33.3, p<0.001) and systolic blood pressure (F=9.2, p=0.003) were associated with abnormal echo findings; for men, increased age (F=12.0, p<0.001) and lower cholesterol (F=4.2, p=0.042) predicted an increase in abnormal findings on echo. CONCLUSIONS: Unrecognised cardiac abnormalities are very common in middle-aged men and women with no overt symptoms. Echo offers the potential to identify the need for early intervention and treatment to improve cardiovascular outcomes.

A case of donepezil-related torsades de pointes.

An 80-year-old woman with Alzheimer's dementia presented with diarrhoea, vomiting and worsening confusion following an increase in donepezil dose from 5 to 10 mg. The ECG revealed prolongation of QTc interval. Soon after admission, she became unresponsive with polymorphic ventricular tachycardia (VT). Cardiopulmonary resuscitation with a 200 J shock was successful in establishing cardiac output. Following the discontinuation of donepezil, the QTc interval normalised and no further arrhythmias were recorded. Treatment with anticholinesterase inhibitors may result in life-threatening VT. Vigilance is required for the identification of this condition in patients presenting with presyncope, syncope or seizures.

Single coronary artery presenting as angina.

The authors present an unusual case of chest pain in an 84-year-old Caucasian woman.

Characteristics of ischaemic human myocardium: a transoesophageal echocardiographic and voltammetric microelectrode study.

Delayed local myocardial power development (primary asynchrony) has been suggested as a marker of ischaemic ventricular dysfunction in humans. However, to prove this, microcirculatory perfusion, microcirculatory oxygenation, and intrinsic mechanical function of the same asynchronous myocardial segment should be studied simultaneously before and after revascularisation. We performed a prospective intraoperative study of 15 patients (age 67 [SD 5] years) at baseline and 30 min after left anterior descending artery grafting. Local tissue perfusion and oxygenation of the anterior left ventricular wall were quantified with a voltammetric microelectrode technique. Transesophageal M-mode echocardiograms and simultaneous high-fidelity left ventricular pressure were measured. Eight patients showed primary asynchrony and 7 did not. Patients with primary asynchrony had local mechanical depression with lower resting values of myocardial work and peak power which increased with surgery. In this group, resting perfusion consistently increased with surgery (32.1 [13] to 54 [31] ml min(-1) 100 g(-1), P < 0.05). In the remaining patients, local work and power were normal, and resting perfusion was consistently higher (90 [9] Ml min(-1) 100 g(-1), P < 0.05 vs primary asynchrony), and fell with surgery. Local tissue oxygen tension was similar in both groups (38 vs 44 mmHg) and did not change with surgery. In patients with chronic coronary artery disease, microcirculatory perfusion, but not pO2, is reduced in regions showing primary asynchrony and impaired mechanical function. Abnormalities in both mechanical function and perfusion normalise within 30 min of revascularisation. These data provide further evidence that primary asynchrony is not only a marker of chronic ischemic ventricular dysfunction, but is associated with a modified contraction pattern in which normal oxygen tension coexists with reduced perfusion.