Contrasting Hemodynamic Mechanisms of Losartan- vs. Atenolol-Based Antihypertensive Treatment: A LIFE Study

BackgroundPharmaceutical differences in central hemodynamics might influence cardiac response to antihypertensive treatment despite similar lowering of brachial blood pressure (BP).MethodsData from all patients with at least two echocardiographic examinations in the Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) echocardiographic substudy (n = 801); high-risk patients on losartan- vs. atenolol-based antihypertensive therapy. Echocardiography was performed annually for 4 years to measure stroke index (SI), heart rate, cardiac index (CI), conduit artery stiffness assessed as pulse pressure/stroke index (PP/SI) and total peripheral resistance index (TPRI).ResultsAtenolol- and losartan-based therapy reduced BP similarly (cumulative difference in mean brachial blood pressure 0.3 mm Hg, P = 0.65). After 4 years the cumulative means of SI and heart rate were 1.8 ml/m(2) higher and 5.7 beats/min lower on atenolol-based treatment, respectively (both P < 0.001). This kept CI below baseline in atenolol-treated patients, whereas in the losartan group CI was unchanged from baseline throughout the study. TPRI was decreased more and remained lower in the losartan group (cumulative difference in mean TPRI 287 dynes/sec(-5)/cm/m(2), P < 0.001). These findings partly explained univariate differences in systolic- and diastolic function indices between the two treatments; fully adjusted losartan was only associated with a smaller left atrial diameter (cumulative mean difference 0.07 cm; 95% confidence intervals, -0.13 to -0.01, P = 0.03).ConclusionsContrasting hemodynamics impacted cardiac response to similar reductions in brachial BP on losartan- vs. atenolol-based therapy. The similar reduction of PP/SI suggests that the antihypertensive regimens used in the LIFE study had comparable effects on arterial stiffness (LIFE study; NCT00338260)American Journal of Hypertension, (2012); doi:10.1038/ajh.2012.81.     

Electrocardiographic left ventricular hypertrophy predicts arrhythmia and mortality in patients with ischemic cardiomyopathy

Purpose

The relatively low incidence of device-treated ventricular arrhythmias in patients with ischemic cardiomyopathy (ICM) who receive implantable cardioverter defibrillators (ICDs) for primary prevention makes improved risk stratification of ICM patients a priority. Although Cornell product (CP) ECG left ventricular hypertrophy (LVH) has been associated with increased mortality in hypertensive patients and population-based studies, whether CP LVH can improve risk stratification of high-risk ICM patients is unclear. The aim of this study is to examine if electrocardiographic LVH predicts mortality and incident ventricular arrhythmia in patients with ICM.

Methods

All-cause mortality was examined in 317 patients with ICM and a history of non-sustained ventricular tachycardia (VT) who underwent electrophysiology testing. Incident VT and ventricular fibrillation (VF) were assessed in ICD recipients (n?=?186). ECG LVH was defined by CP criteria: [(R _aVL?+?S _V3)?+?6?mm in women]?×?QRS duration >2,440?mm?ms.

Results

During 3?years of follow-up, mortality was 20% (64 of 317) and death or incident VT or VF occurred in 35% of ICD recipients. CP LVH was associated with significantly greater 3-year mortality (28% vs 15%, p?=?0.015) and 3-year mortality or incident VT/VF in ICD patients (48% vs 35%, p?=?0.011). In Cox multivariate models, CP LVH was an independent predictor of mortality in all patients (hazard ratio (HR) 1.81, 95% confidence interval (CI) 1.11?C2.97, p?=?0.020) and of the composite endpoint of mortality or incident ventricular arrhythmia in ICD patients (HR 1.82, 95% CI 1.12?C3.00, p?=?0.016).

Conclusions

ECG LVH using CP criteria may enhance risk stratification in high-risk patients with ICM.     

The economic burden of preventable adverse drug reactions: a systematic review of observational studies

Introduction: Adverse drug reactions (ADRs) are an important cause of morbidity and mortality worldwide. They are associated with healthcare costs due to hospital admissions or prolonged length of stay, as well as additional interventions. The aim of this study was to conduct a systematic review of observational studies to evaluate the economic impact of preventable ADRs.

Areas covered: Published observational research investigating the cost of preventable ADRs in Western countries (limited to the USA and European countries).

Expert opinion: Several reviews have been carried out in the field of the ADR epidemiology but fewer reviews have investigated the economic impact of ADRs, and at the time of writing, none has focused on preventable ADRs. The reason why future research should focus on the costs of preventable ADRs is that both the costs and the negative clinical outcomes are preventable, and as such, are a key point of public health policy action. Nevertheless, the present review highlights an important and sobering limitation of published research on the cost of preventable ADRs, of which the major limitation is the heterogeneity in methods and in reporting which limit what can be known through the summarizing work of a systematic review.     

Duration of ejection in aortic stenosis: effect of stroke volume and pressure gradient

The theoretical effect of variable ventricular function on left ventricular ejection time in aortic stenosis was predicted by applying data measured in 52 patients with pure aortic stenosis to equations derived from the relations of Gorlin and Gorlin and Weissler et al. Ejection time and aortic valve area are not, of necessity, linearly related because (Formula: see text) where LVET is left ventricular ejection time, k is a constant, SV is stroke volume, PG is mean aortic pressure gradient and AVA is aortic valve area. When the patients were separated into performance groups on the basis of cardiac index (at 2.8 liters/min per m2), the linear regression relating the measured SV/square root PG with valve area in 18 patients with normal function (SV/square root PG = 11.1 AVA + 2.0, r = 0.969, p less than 0.001) predicted ejection time prolongation with decreasing valve area. In 34 patients with poor function, however, the decrease in SV/square root PG with decreasing valve area was more marked (SV/square root PG = 12.6 AVA + 0.4, r = 0.894, p less than 0.001), predicting a shorter ejection time at any given valve area in this group. As predicted by the effect of valve area on the equation, ejection time becomes most variable at a small aortic valve area. Independent ejection time measurement in these patients validated the predicted effect.     

The effects of recombinant-DNA-derived interferons on the growth of myeloid progenitor cells

Interferons (IFNs) have been shown to have significant effects on hematopoietic cell growth. Previous studies defining these effects have utilized mouse and human alpha-, beta-, and gamma-IFN isolated from supernatants of stimulated cells. Despite purification, the possible presence of other lymphokines and soluble factors remains a concern. In this study, the effects of gene-cloned alpha- and gamma-IFN on colony- forming units of granulocyte/macrophage (CFU-GM) progenitors cultured from the peripheral blood of normal volunteers were examined. In addition, blast cell colonies from one patient with acute myelogenous leukemia (AML) were studied. The growth of normal CFU-GM and AML blast cell colonies was inhibited in a dose-dependent manner by gamma- and alpha-IFN. gamma-IFN was ten to 100 times more potent than alpha-IFN in that this species of IFN reduced colony formation by greater than 50% at concentrations of less than 15 antiviral U/mL. The effects of gamma- IFN were neutralized by a monoclonal antibody specific for gamma-IFN. These in vitro studies indicate that human gamma-IFN may be an important modulator of myelopoiesis. Although these data indicate a possible efficacy of gamma-IFN in the treatment of AML, the in vitro results should be considered for their in vivo significance.     

Diagnostic performance of a computer-based ECG rhythm algorithm

We examined the accuracy of computer-based rhythm interpretation from one electrocardiograph manufacturer (GE Healthcare Technologies MUSE software 005C) in 4297 consecutive recordings in a university hospital setting. Overreading was performed by either of 2 experienced cardiologists, and all disagreements with the initial computer rhythm statement were reviewed by the second cardiologist to achieve physician consensus used as the "gold standard" for rhythm diagnosis. Overall, 13.2% (565/4297) of computer-based rhythm statements required revision, but excluding tracings with pacemakers, the revision rate was 7.8% (307/3954), including 3.8% involving the primary rhythm diagnosis and 3.9% involving definition of ectopic complexes. The false-negative rate for sinus rhythm was only 1.3%, but a computer diagnosis of sinus rhythm was incorrect in 9.9% of other rhythms. The false-negative rate for atrial fibrillation was 9.2%, whereas a computer diagnosis of atrial fibrillation was incorrect in 1.1% of other rhythms, including sinus. Computer diagnosis of paced rhythms remains problematic, and physician overreading to correct computer-based electrocardiogram rhythm diagnoses remains mandatory.