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See detailPacing-induced cardiomyopathy: pathophysiological insights through matrix metalloproteinases.
Ahmed, Fozia Z.; Khattar, Rajdeep S.; Zaidi, Amir M. et al

in Heart failure reviews (2013)

Pacing-induced ventricular dysfunction and pacing-induced cardiomyopathy (PiCMP) are recognized complications of chronic right ventricular pacing. Alterations in myocardial perfusion and sympathetic ... [more ▼]

Pacing-induced ventricular dysfunction and pacing-induced cardiomyopathy (PiCMP) are recognized complications of chronic right ventricular pacing. Alterations in myocardial perfusion and sympathetic innervation contribute to the development of pacing-induced heart disease. However, it is unlikely that these are the only processes involved. Matrix metalloproteinases (MMPs) are proteolytic enzymes that degrade the collagenous extracellular matrix and play a central role in left ventricular remodelling during the development of heart failure. While the pathophysiological mechanisms and altered MMP expression that occur in chronic pressure overload, ischaemic and non-ischaemic dilated cardiomyopathy have been defined, those that occur in the clinical setting of pacing-induced ventricular dysfunction and PiCMP have not been reported. Here we review the clinical epidemiology of pacing-induced ventricular dysfunction and discuss how data derived from animal models provide insight into how changes in MMP expression and function contribute to the development of PiCMP. The review concludes by exploring pacing strategies that may be used to prevent pacing-induced ventricular dysfunction. [less ▲]

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See detailWhat strategies are effective for exercise adherence in heart failure? A systematic review of controlled studies.
Tierney, Stephanie; Mamas, Mamas; Woods, Stephen et al

in Heart failure reviews (2012), 17(1), 107-15

Physical activity is recommended for people with stable heart failure (HF), because it is known to improve quality of life and health outcomes. However, adherence to this recommendation has been poor in ... [more ▼]

Physical activity is recommended for people with stable heart failure (HF), because it is known to improve quality of life and health outcomes. However, adherence to this recommendation has been poor in many studies. A systematic review was conducted to examine the effectiveness of strategies used to promote exercise adherence in those with HF. The following databases were searched for relevant literature published between January 1980 and December 2010: British Nursing Index; CINAHL; Cochrane Library; Embase; Medline and PsycINFO. Papers with a control group focused on adults with HF that measured exercise or physical activity adherence were included. Nine randomised controlled trials were identified, involving a total of 3,231 patients (range 16-2,331). Six of these studies were informed by specific psychological theories. Positive outcomes occurred in the short-term from interventions using approaches such as exercise prescriptions, goal setting, feedback and problem-solving. However, longer-term maintenance of exercise was less successful. There was some support for interventions underpinned by theoretical frameworks, but more research is required to make clearer recommendations. Addressing self-efficacy in relation to exercise may be a particularly useful area to consider in this respect. [less ▲]

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See detailWhat influences physical activity in people with heart failure?: a qualitative study.
Tierney, Stephanie; Elwers, Heather; Sange, Chandbi et al

in International journal of nursing studies (2011), 48(10), 1234-43

BACKGROUND: Research has highlighted the benefits of physical activity for people with stable heart failure in improving morbidity and quality of life. However, adherence to exercise among this patient ... [more ▼]

BACKGROUND: Research has highlighted the benefits of physical activity for people with stable heart failure in improving morbidity and quality of life. However, adherence to exercise among this patient group is low. Barriers and enablers to sustained physical activity for individuals with heart failure have been little investigated. OBJECTIVES: To explore reasons why people with heart failure do and do not engage in regular physical activity. DESIGN: A qualitative, interview-based investigation. SETTINGS: Three heart failure clinics held at hospitals in the UK. PARTICIPANTS: Purposive sampling was adopted to provide maximum variation in terms of gender, age, heart failure duration and severity, and current activity levels. Twenty two patients (7=female) were interviewed, aged between 53 and 82 years. METHODS: Semi-structured interviews were conducted via telephone. These were recorded and transcribed verbatim. Framework analysis was applied to collected data. RESULTS: Interviewees' narratives suggested that adopting positive health behaviours was complex, affected by internal and external factors. This was reflected in the four themes identified during analysis: fluctuating health; mental outlook; others' expectations; environmental influences. Failure to exercise arose because of symptoms, co-morbidities, poor sense of self as active and/or lack of perceived benefit. Likewise, encouragement from others and inclement weather affected exercising. CONCLUSIONS: Areas identified during interviews as influencing activity levels relate to those commonly found in behavioural change theories, namely perceived costs and benefits, self-efficacy and social support. These are concepts that practitioners may consider when devising interventions to assist patients with heart failure in undertaking and maintaining regular exercise patterns. [less ▲]

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See detailIntegration of metabolomics in heart disease and diabetes research: current achievements and future outlook.
Dunn, Warwick B.; Goodacre, Royston; Neyses, Ludwig UL et al

in Bioanalysis (2011), 3(19), 2205-22

Metabolomics is an emerging and powerful discipline that provides an accurate and dynamic picture of the phenotype of mammalian systems through the study of endogenous and exogenous metabolites in cells ... [more ▼]

Metabolomics is an emerging and powerful discipline that provides an accurate and dynamic picture of the phenotype of mammalian systems through the study of endogenous and exogenous metabolites in cells, tissues, culture supernatants as well as biofluids. In the last 5 years an increase in the number of metabolomic investigations of cardiovascular diseases and diabetes has been observed. In this article the experimental strategies applied and recent examples of their application in disease and drug efficacy/toxicity biomarker detection and the employment for the discovery of new molecular pathophysiological processes related to disease onset and progression, as well as their usefulness in drug efficacy/toxicity, will be reviewed. An outlook of the requirements for future successes will also be discussed. [less ▲]

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See detailThe role of metabolites and metabolomics in clinically applicable biomarkers of disease.
Mamas, Mamas; Dunn, Warwick B.; Neyses, Ludwig UL et al

in Archives of toxicology (2011), 85(1), 5-17

Metabolomics allows the simultaneous and relative quantification of thousands of different metabolites within a given sample using sensitive and specific methodologies such as gas or liquid chromatography ... [more ▼]

Metabolomics allows the simultaneous and relative quantification of thousands of different metabolites within a given sample using sensitive and specific methodologies such as gas or liquid chromatography coupled to mass spectrometry, typically in discovery phases of studies. Biomarkers are biological characteristics that are objectively measured and evaluated as indicators of normal biological processes, pathological processes or pharmacologic responses to a therapeutic intervention. Biomarkers are widely used in clinical practice for the diagnosis, assessment of severity and response to therapy in a number of clinical disease states. In human studies, metabolomics has been applied to define biomarkers related to prognosis or diagnosis of a disease or drug toxicity/efficacy and in doing so hopes to provide greater pathophysiological understanding of disease or therapeutic toxicity/efficacy. This review discusses the application of metabolomics in the discovery and subsequent application of biomarkers in the diagnosis and management of inborn errors of metabolism, cardiovascular disease and cancer. We critically appraise how novel biomarkers discovered through metabolomic analysis may be utilized in future clinical practice by addressing the following three fundamental questions: (1) Can the clinician measure them? (2) Do they add new information? (3) Do they help the clinician to manage patients? Although a number of novel biomarkers have been discovered through metabolomic studies of human diseases in the last decade, none have currently made the transition to routine use in clinical practice. Metabolites identified from these early studies will need to form the basis of larger, prospective, externally validated studies in clinical cohorts for their future use as biomarkers. At this stage, the absolute quantification of these biomarkers will need to be assessed epidemiologically, as will the ultimate deployment in the clinic via routine biochemistry, dip stick or similar rapid at- or near-patient care technologies. [less ▲]

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See detailPlasma membrane calcium pump (PMCA4)-neuronal nitric-oxide synthase complex regulates cardiac contractility through modulation of a compartmentalized cyclic nucleotide microdomain.
Mohamed, Tamer M. A.; Oceandy, Delvac; Zi, Min et al

in The Journal of biological chemistry (2011), 286(48), 41520-9

Identification of the signaling pathways that regulate cyclic nucleotide microdomains is essential to our understanding of cardiac physiology and pathophysiology. Although there is growing evidence that ... [more ▼]

Identification of the signaling pathways that regulate cyclic nucleotide microdomains is essential to our understanding of cardiac physiology and pathophysiology. Although there is growing evidence that the plasma membrane Ca(2+)/calmodulin-dependent ATPase 4 (PMCA4) is a regulator of neuronal nitric-oxide synthase, the physiological consequence of this regulation is unclear. We therefore tested the hypothesis that PMCA4 has a key structural role in tethering neuronal nitric-oxide synthase to a highly compartmentalized domain in the cardiac cell membrane. This structural role has functional consequences on cAMP and cGMP signaling in a PMCA4-governed microdomain, which ultimately regulates cardiac contractility. In vivo contractility and calcium amplitude were increased in PMCA4 knock-out animals (PMCA4(-/-)) with no change in diastolic relaxation or the rate of calcium decay, showing that PMCA4 has a function distinct from beat-to-beat calcium transport. Surprisingly, in PMCA4(-/-), over 36% of membrane-associated neuronal nitric-oxide synthase (nNOS) protein and activity was delocalized to the cytosol with no change in total nNOS protein, resulting in a significant decrease in microdomain cGMP, which in turn led to a significant elevation in local cAMP levels through a decrease in PDE2 activity (measured by FRET-based sensors). This resulted in increased L-type calcium channel activity and ryanodine receptor phosphorylation and hence increased contractility. In the heart, in addition to subsarcolemmal calcium transport, PMCA4 acts as a structural molecule that maintains the spatial and functional integrity of the nNOS signaling complex in a defined microdomain. This has profound consequences for the regulation of local cyclic nucleotide and hence cardiac beta-adrenergic signaling. [less ▲]

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See detailWhat can we learn from patients with heart failure about exercise adherence? A systematic review of qualitative papers.
Tierney, Stephanie; Mamas, Mamas; Skelton, Dawn et al

in Health psychology : official journal of the Division of Health Psychology, American Psychological Association (2011), 30(4), 401-10

OBJECTIVES: Keeping physically active has been shown to bring positive outcomes for patients diagnosed with heart failure (HF). However, a number of individuals with this health problem do not undertake ... [more ▼]

OBJECTIVES: Keeping physically active has been shown to bring positive outcomes for patients diagnosed with heart failure (HF). However, a number of individuals with this health problem do not undertake regular exercise. A review of extant qualitative research was conducted to explore what it can tell us about barriers and enablers to physical activity among people with HF. METHODS: A systematic search, involving electronic databases and endeavors to locate gray literature, was carried out to identify relevant qualitative studies published from 1980 onward. Data from retrieved papers were combined using framework analysis. Papers read in full numbered 32, and 20 were included in the review. RESULTS: Synthesis of results from the 20 studies resulted in 4 main themes: Changing soma, negative emotional response, adjusting to altered status, and interpersonal influences. How individuals responded to their diagnosis and their altered physical status related to their activity levels, as did the degree of encouragement to exercise coming from family, friends, and professionals. These findings can be connected to the theory of behavioral change developed by Bandura, known as social cognitive theory (SCT). CONCLUSIONS: SCT may be a useful framework for developing interventions to support patients with HF in undertaking and maintaining regular exercise patterns. Specific components of SCT that practitioners may wish to consider include self-efficacy and outcome expectancies. These were issues referred to in papers for the systematic review that appear to be particularly related to exercise adherence. [less ▲]

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See detailUse of the sheathless guide catheter during routine transradial percutaneous coronary intervention: a feasibility study.
Mamas, Mamas; D'Souza, Savio; Hendry, Cara et al

in Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions (2010), 75(4), 596-602

OBJECTIVE: The aim of this study is to investigate the feasibility of using a 6.5 Fr sheathless guide catheter as a default system in transradial (TRA) percutaneous coronary intervention (PCI). BACKGROUND ... [more ▼]

OBJECTIVE: The aim of this study is to investigate the feasibility of using a 6.5 Fr sheathless guide catheter as a default system in transradial (TRA) percutaneous coronary intervention (PCI). BACKGROUND: TRA PCI has been shown to reduce mortality rates through a reduction in access site related bleeding complications compared with procedures performed though a femoral approach. Complications associated with the TRA route increase with the size of sheath used. These complications may be reduced by the use of a sheathless guide catheter system (Asahi Intecc, Japan) that is 1-2 Fr sizes smaller in diameter than the corresponding introducer sheath. METHODS: We performed PCI in 100 consecutive cases using 6.5 Fr sheathless guides to determine the procedural success, rates of symptomatic radial spasm and radial occlusion. RESULTS: Procedural success using the 6.5 Fr sheathless guide catheter system was 100% with no cases requiring conversion to a conventional guide and catheter system. There were no procedural complications recorded associated with the use of the catheter. Adjunctive devices used in this cohort included IVUS, stent delivery catheters, distal protection devices, and simple thrombectomy catheters. The rate of radial spasm was 5% and the rate of radial occlusion at 2 months was 2%. CONCLUSION: Use of the 6.5 Fr sheathless guide catheter system, which has an outer diameter <5 Fr sheath, as the default system in routine PCI is feasible with a high rate of procedural success via the radial artery. [less ▲]

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See detailHow common is asymptomatic paroxysmal atrial fibrillation in chronic heart failure?
Caldwell, Jane; Mamas, Mamas; Garratt, Clifford et al

in Scandinavian cardiovascular journal : SCJ (2008), 42(6), 366367

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