Design features of the Avasimibe and Progression of coronary Lesions assessed by intravascular UltraSound (A-PLUS) clinical trial

Background Although statins have been shown to be beneficial in the management of hyperlipidemia and the reduction of cardiovascular morbidity and mortality, rates of major cardiovascular events remain high despite their use. Inhibition of the acyl coenzyme A: cholesterol acyltransferase (ACAT) enzyme in the arterial wall may prevent excess accumulation of cholesteryl esters in macrophages. In addition to ACAT inhibitor monotherapy, combination of a statin with an ACAT inhibitor may be a promising approach to further prevent the progression of atherosclerosis. Methods This report describes the design and methodologic features of a double-blind, randomized, placebo-controlled trial to assess the effect of the ACAT inhibitor avasimibe at 50-, 250-, and 750-mg daily dosages on the progression of coronary atherosclerosis as assessed by intravascular ultrasound (IVUS). All patients receive background lipid-lowering therapy when necessary. The study population consists of patients with at least one 20% to 50% diameter stenosis in a coronary artery with a reference diameter of ≥2.5 mm. IVUS and coronary angiography are performed at baseline and repeated at 24 months. The primary study end point is the change from baseline in plaque volume in a 30-mm segment of the coronary artery assessed by 3-dimensional IVUS. Several other IVUS and angiographic end points are measured. Conclusions The Avasimibe and Progression of coronary Lesions assessed by intravascular UltraSound (A-PLUS) trial is among the first large imaging trials to use IVUS as a primary end point and assesses the effects of the ACAT inhibitor avasimibe on atherosclerosis progression. (Am Heart J 2002;144:589-96.)     

Positive pressure ventilation in the management of acute and chronic cardiac failure: a systematic review and meta-analysis

Chronic heart failure (CHF) is a common condition and is associated with excess morbidity and mortality, in spite of the many advances in its treatment. Chronic stable heart failure is also associated with an increased incidence of sleep-related breathing disorders, such as central sleep apnoea (CSA) and Cheyne Stokes respiration (CSR). Continuous positive airways pressure (CPAP) has been shown to alleviate the symptoms of CHF, improve left ventricular function and oxygenation. To a certain extent, CPAP also abolishes sleep-related breathing disorders in patients with chronic heart failure. In patients with acute pulmonary oedema, the use of positive pressure ventilation improves cardiac haemodynamic indices, as well as symptoms and oxygenation, and is associated with a lower need for intubation. However, some studies have cast doubts about its safety and suggest a higher rate of myocardial infarction associated with its use. In our opinion, non-invasive positive pressure ventilation and CPAP offers an adjunctive mode of therapy in patients with acute pulmonary oedema and chronic heart failure, who may not be suitable for intubation and in those not responsive to conventional therapies. Non-invasive ventilation also helps to improve oxygenation in those patients with exhaustion and respiratory acidosis. Many trials are still ongoing and the results of these studies would throw more light on the present role of non-invasive ventilation in the management of CHF.     

Evaluación multimodal de la degeneración estructural de válvulas percutáneas en el seguimiento a largo plazo

Introduction and objectivesWe assessed the long-term hemodynamic performance of transcatheter heart valve (THV) by paired transthoracic echocardiography (TTE), and the incidence, characteristics and factors associated with THV structural valve degeneration (SVD).MethodsA total of 212 patients who underwent transcatheter aortic valve replacement and had a potential follow-up > 5 years with at least 1 TTE ≥ 1-year postprocedure were included. All patients had a TTE at 1 to 5 years and 36 had another one at 6 to 10 years. SVD was defined as subclinical (increase > 10 mmHg in mean transvalvular gradient +  decrease > 0.3 cm² in valve area and/or new-onset mild or moderate aortic regurgitation) and clinically relevant (increase > 20 mmHg in mean transvalvular gradient + decrease > 0.6 cm² in valve area and/or new-onset moderate-to-severe aortic regurgitation). Fifteen patients had a transesophageal echocardiography at the time of SVD diagnosis, and 85 an opportunistic computed tomography examination at 1 (0.5-2) years.ResultsTransvalvular mean gradient increased and valve area decreased over time (P < .01). At 8 years of follow-up, SVD occurred in 30.2% of patients (clinically relevant: 9.3%). Transesophageal echocardiography revealed thickened and reduced-mobility leaflets in 80% and 73% of SVD cases, respectively. No baseline or procedural factors were associated with SVD. THV underexpansion (3.5%) or eccentricity (8.2%) had no impact on valve hemodynamics/SVD at follow-up.ConclusionsA gradual THV hemodynamic deterioration occurred throughout a 10-year period, leading to SVD in ～30% of patients (clinically relevant in < 10%). Leaflet morphology/mobility were frequently impaired in SVD cases, but THV geometry did not influence valve hemodynamics or SVD.     

High-frequency oscillatory ventilation in adults: the Toronto experience

STUDY OBJECTIVES: To review the clinical experience with high-frequency oscillatory ventilation (HFOV) in three medical-surgical ICUs in Toronto, ON, Canada, and to describe patient characteristics, HFOV strategies, and outcomes. DESIGN AND PATIENTS: Retrospective chart review of all patients treated with HFOV at three academic university-affiliated ICUs since 1998. The data extracted included patient demographics, etiology of respiratory failure, ventilator settings, and gas exchange and cardiovascular data from baseline to 72 h of treatment, as well as at the transition from HFOV to conventional ventilation (CV). Heart rate and BP were recorded at regular intervals in all patients, and hemodynamic data were recorded in 32 patients who had pulmonary artery catheters in place. Cointerventions and ICU mortality were also recorded. MEASUREMENTS AND RESULTS: A total of 156 adults (67 women and 89 men; mean [+/- SD] age, 48 +/- 18 years; mean acute physiology and chronic health evaluation [APACHE] II score, 23.8 +/- 7.5) with severe ARDS (ie, mean Pao(2)/fraction of inspired oxygen [Fio(2)] ratio, 91 +/- 48 mm Hg; mean oxygenation index [OI], 31 +/- 14) who had received CV for a duration of 5.6 +/- 7.6 days underwent 171 trials of HFOV. HFOV was discontinued within 4 h in 19 patients (12%) because of difficulties with oxygenation, ventilation, or hemodynamics. Pao(2)/Fio(2) ratios and OI ([Fio(2) x mean airway pressure x 100]/Pao(2)) improved significantly with the application of HFOV, and this benefit persisted for the 72-h study duration. Significant changes in hemodynamics following HFOV initiation included an increase in central venous pressure and a reduction in cardiac output (throughout the 72 h), and an increase in pulmonary artery occlusion pressure (at 3 and 6 h). Patients were treated with HFOV for 5.1 +/- 6.3 days. The 30-day mortality rate was 61.7%. Pneumothorax occurred in 21.8% of patients, 43.6% of patients were treated with inhaled nitric oxide, and 37.2% of patients were treated with steroids. Independent predictors of mortality on multivariate analysis were older age, higher APACHE II score, lower pH at the initiation of HFOV, and a greater number of days receiving CV prior to HFOV. CONCLUSIONS: HFOV has beneficial effects on Pao(2)/Fio(2) ratios and OI, and may be an effective rescue therapy for adults with severe oxygenation failure. The early institution of HFOV may be advantageous.     

Amiodarone-associated optic neuropathy: a critical review

Although amiodarone is the most commonly prescribed anti-arrhythmic drug, its use is limited by serious toxicities, including optic neuropathy. Current reports of amiodarone-associated optic neuropathy identified from the Food and Drug Administration's Adverse Event Reporting System and published case reports were reviewed. A total of 296 reports were identified: 214 from the Adverse Event Reporting System, 59 from published case reports, and 23 from adverse events reports for patients enrolled in clinical trials. Mean duration of amiodarone therapy before vision loss was 9 months (range 1-84 months). Insidious onset of amiodarone-associated optic neuropathy (44%) was the most common presentation, and nearly one third were asymptomatic. Optic disk edema was present in 85% of cases. Following drug cessation, 58% had improved visual acuity, 21% were unchanged, and 21% had further decreased visual acuity. Legal blindness (<20/200) was noted in at least one eye in 20% of cases. Close ophthalmologic surveillance of patients during the tenure of amiodarone administration is warranted.