A review of the external validity of clinical trials with beta-blockers in heart failure

Beta-blockers (BBs) are the mainstay prognostic medication for all stages of chronic heart failure (CHF). There are many classes of BBs, each of which has varying levels of evidence to support its efficacy in CHF. However, most CHF patients have one or more comorbid conditions such as diabetes, renal impairment, and/or atrial fibrillation. Patient enrollment to randomized controlled trials (RCTs) often excludes those with certain comorbidities, particularly if the symptoms are severe. Consequently, the extent to which evidence drawn from RCTs is generalizable to CHF patients has not been well described. Clinical guidelines also underrepresent this point by providing generic advice for all patients. The aim of this review is to examine the evidence to support the use of BBs in CHF patients with common comorbid conditions.We searched MEDLINE, PubMed, and the reference lists of reviews for RCTs, post hoc analyses, systematic reviews, and meta-analyses that report on use of BBs in CHF along with patient demographics and comorbidities.In total, 38 studies from 28 RCTs were identified, which provided data on six BBs against placebo or head to head with another BB agent in ischemic and nonischemic cardiomyopathies. Several studies explored BBs in older patients. Female patients and non-Caucasian race were underrepresented in trials. End points were cardiovascular hospitalization and mortality. Comorbid diabetes, renal impairment, or atrial fibrillation was detailed; however, no reference to disease spectrum or management goals as a focus could be seen in any of the studies. In this sense, enrollment may have limited more severe grades of these comorbidities.RCTs provide authoritative information for a spectrum of CHF presentations that support guidelines. RCTs may provide inadequate information for more heterogeneous CHF patient cohorts. Greater Phase IV research may be needed to fill this gap and inform guidelines for a more global patient population.Pupalan Iyngkaran, Samia R. Toukhsati, Merlin C. Thomas, Michael V. Jelinek, David L. Hare and John D. Horowit

Making sense of health care delivery Where does the close to community health care worker fit in? – The case for congestive heart failure

Close to community health care workers (CTC-HCW) is an increasingly used term to describe the emergence of a new partner in health services delivery. In strengthening arguments for this part of the health workforce the authorities, health staffers, supporters, sceptics and perhaps clients will look to the academicians and the evidence base to determine the fate of this group. There is no doubt, CTC-HCW are a vital resource, whose importance is tied to socio-demo-geographic variables. Regardless of what the common perceptions of its importance are, the evolving evidence base could suggest either way. In this short commentary we would like to highlight the importance of a balanced and common sense approach in these arguments. An important example is heart failure where the majority have an associated comorbidity and one in four would also suffer with cognitive or mood disturbances. It is unclear how the CTC-HCW would fare for this devastating syndrome. In moving forward it is important we understand there are: strengths and limitations in the evidence gathering processes; indecision as to the questions; uncertainty of the starting points to gather evidence; and sociodemogeographic biases, which have to be factored before determining the fate of this much needed health care resource

Cardiac Imaging in Heart Failure with Comorbidities.

Imaging modalities stand at the frontiers for progress in congestive heart failure (CHF) screening, risk stratification and monitoring. Advancements in echocardiography (ECHO) and Magnetic Resonance Imaging (MRI) have allowed for improved tissue characterizations, cardiac motion analysis, and cardiac performance analysis under stress. Common cardiac comorbidities such as hypertension, metabolic syndromes and chronic renal failure contribute to cardiac remodeling, sharing similar pathophysiological mechanisms starting with interstitial changes, structural changes and finally clinical CHF. These imaging techniques can potentially detect changes earlier. Such information could have clinical benefits for screening, planning preventive therapies and risk stratifying patients. Imaging reports have often focused on traditional measures without factoring these novel parameters. This review is aimed at providing a synopsis on how we can use this information to assess and monitor improvements for CHF with comorbidities

Shortness of breath in clinical practice: A case for left atrial function and exercise stress testing for a comprehensive diastolic heart failure workup.

The symptom cluster of shortness of breath (SOB) contributes significantly to the outpatient workload of cardiology services. The workup of these patients includes blood chemistry and biomarkers, imaging and functional testing of the heart and lungs. A diagnosis of diastolic heart failure is inferred through the exclusion of systolic abnormalities, a normal pulmonary function test and normal hemoglobin, coupled with diastolic abnormalities on echocardiography. Differentiating confounders such as obesity or deconditioning in a patient with diastolic abnormalities is difficult. While the most recent guidelines provide more avenues for diagnosis, such as incorporating the left atrial size, little emphasis is given to understanding left atrial function, which contributes to at least 25% of diastolic left ventricular filling; additionally, exercise stress testing to elicit symptoms and test the dynamics of diastolic parameters, especially when access to the "gold standard" invasive tests is lacking, presents clinical translational gaps. It is thus important in diastolic heart failure work up to understand left atrial mechanics and the role of exercise testing to build a comprehensive argument for the diagnosis of diastolic heart failure in a patient presenting with SOB

Bedside–to-Bench Translational Research for Chronic Heart Failure: Creating an Agenda for Clients Who Do Not Meet Trial Enrollment Criteria

Congestive heart failure (CHF) is a chronic condition usually without cure. Significant developments, particularly those addressing pathophysiology, mainly started at the bench. This approach has seen many clinical observations initially explored at the bench, subsequently being trialed at the bedside, and eventually translated into clinical practice. This evidence, however, has several limitations, importantly the generalizability or external validity. We now acknowledge that clinical management of CHF is more complicated than merely translating bench-to-bedside evidence in a linear fashion. This review aims to help explore this evolving area from an Australian perspective. We describe the continuation of research once core evidence is established and describe how clinician–scientist collaboration with a bedside-to-bench view can help enhance evidence translation and generalizability. We describe why an extension of the available evidence or generating new evidence is occasionally needed to address the increasingly diverse cohort of patients. Finally, we explore some of the tools used by basic scientists and clinicians to develop evidence and describe the ones we feel may be most beneficial

Risk stratification for coronary artery disease in multi-ethnic populations: Are there broader considerations for cost efficiency?

Coronary artery disease (CAD) screening and diagnosis are core cardiac specialty services. From symptoms, autopsy correlations supported reductions in coronary blood flow and dynamic epicardial and microcirculatory coronaries artery disease as etiologies. While angina remains a clinical diagnosis, most cases require correlation with a diagnostic modality. At the onset of the evidence building process much research, now factored into guidelines were conducted among population and demographics that were homogenous and often prior to newer technologies being available. Today we see a more diverse multi-ethnic population whose characteristics and risks may not consistently match the populations from which guideline evidence is derived. While it would seem very unlikely that for the majority, scientific arguments against guidelines would differ, however from a translational perspective, there will be populations who differ and importantly there are cost-efficacy questions, e.g., the most suitable first-line tests or what parameters equate to an adequate test. This article reviews non-invasive diagnosis of CAD within the context of multi-ethnic patient populations

Cardio-Renal Syndrome: New Perspective in Diagnostics

Chronic heart failure and chronic renal failure are at epidemic proportions. These patients have significantly altered cardiac, renal, and all-cause outcomes. Much of the current research has focused on treating these individual organs in isolation. Although there are positive data on outcomes with neurohormonal modulation, they, however, remain underused. At present, data lacks for novel treatment options, while evidence continues to point at significantly worsened prognosis. Current diagnostic tools that detect acute changes in renal function or renal injury appear retrospective, which often hinder meaningful diagnostic and therapeutic decisions. This review is aimed at exploring the importance of accurate assessment of renal function for the heart failure patient by providing a synopsis on cardio-renal physiology and establishing the possibility of novel approaches in bridging the divide. Semin Nephrol 32:3-17 (C) 2012 Elsevier Inc. All rights reserved