Pharmaceutical care of patients with congestive heart failure: Interventions and outcomes

We evaluated a structured pharmaceutical care program for elderly patients (> 65 yrs) with congestive heart failure (CHF) based on objective measures of disease control, quality of life, and use of health care facilities in a randomized, controlled, longitudinal, prospective clinical trial. The 42 patients in group A received education from a pharmacist on the disease and its treatment, and lifestyle changes that could help control symptoms. Patients also were encouraged to monitor their symptoms and comply with prescribed drug therapy. If necessary, dosage regimens were simplified in liaison with hospital physicians. The 41 control patients (group B) received standard care. The following outcome measures were assessed in all patients at baseline (before the start of the trial) and at 3, 6, 9, and 12 months: 2-minute walk test, blood pressure, body weight, pulse, forced vital capacity, quality of life [disease-specific (Minnesota Living with Heart Failure questionnaire) and generic (SF-36)], knowledge of symptoms and drugs, compliance with therapy, and use of health care facilities (hospital admissions, visits to emergency room, emergency calls). Patients in group A showed improved compliance with drug therapy, which in turn improved their exercise capacity compared with those in group B; education on management of symptoms, lifestyle changes, and dietary recommendations were also of benefit. Group A patients significantly improved knowledge of their drug therapy over the 12-month study and had fewer hospital admissions compared with group B patients. They also had improved outcomes compared with group B, despite the small samples. An extension of this trial to other sites with pooling of results would provide additional evidence of the value of this structured program in elderly patients with CHF.

Modalities of exercise training on liver fat accretion and inflammatory markers in ovariectomized rats

Les facteurs de risque des maladies cardiovasculaires, telle, que la détérioration du profil lipidique, deviennent plus prononcés après la ménopause, ce qui fait de la maladie coronarienne, l’une des principales causes de décès chez les femmes ménopausées. Une proportion importante de femmes prennent du poids après la ménopause en particulier dans la région abdominale entraînant par conséquent des perturbations métaboliques. Des données récentes suggèrent également que l’absence des œstrogènes observée à la ménopause favorise le développement de la stéatose hépatique. Cette dernière a été incriminée pour incriminée dans le développement de la résistance à l'insuline, et est de ce fait considérée comme une composante hépatique du syndrome métabolique. Il est impératif d'établir des stratégies visant à contrecarrer l'accumulation de graisse dans le foie et l’accroissement du tissu adipeux chez les femmes ménopausées, en tenant compte que l'utilisation de l'hormonothérapie substitutive est de nos jours moins soutenue. Les quatre études de la présente thèse ont été conduites pour tenter de fournir des informations sur le traitement et la prévention de l’augmentation de la masse graisseuse et de la stéatose hépatique qu’entraîne la suppression des œstrogènes, à travers les modifications du mode de vie (diète et exercice physique) chez la rate ovariectomizée (Ovx); un modèle animal de la ménopause. Dans les deux premières études nous nous sommes concentrés sur l’augmentation de la masse graisseuse et sa reprise suite à une perte de poids. Dans la première étude, nous avons montré que les rates Ovx qui ont suivi un programme de restriction alimentaire (FR) ont diminué significativement (P < 0.01) leur poids corporel, leur contenu en graisses intra-abdominales ainsi que leurs triacylglycérols (TAG) hépatiques, comparativement aux rates Ovx nourries à la diète normale. De plus, l’entraînement en résistance (RT) a prévenu la reprise de poids corporel ainsi que l’accroissement du tissu adipeux et l’accumulation de lipides dans le foie des rates Ovx, après l’arrêt du régime amaigrissant. Les résultats de la deuxième étude ont confirmé l'efficacité de la restriction alimentaire associée à l’entraînement en résistance (FR + RT) dans la réduction du poids corporel, des lipides dans le foie et le tissu adipeux chez les rates Ovx. Tenant compte des résultats de notre première étude, l’entraînement en résistance seulement a constitué un atout pour atténuer le poids corporel et la masse grasse reprise par les rates Ovx suite à un programme de perte de poids (FR + RT); bien que l'impact ait été moindre comparé au maintien seul de la restriction alimentaire. De la même manière que la supplémentation en œstrogènes, les résultats de la troisième étude indiquent que l'entraînement en endurance mené concurremment avec l’ovariectomie a significativement atténué l'accumulation de lipides dans le foie ainsi que dans le tissu adipeux. Toutefois, l’entraînement en endurance effectué avant l'ovariectomie n'a pas protégé contre l'accumulation des graisses qu’entraîne l'ovariectomie, si celui-ci est interrompu après l'ovariectomie. Enfin, pour compléter les résultats antérieurs, nous avons montré dans la quatrième étude que l’expression des gènes impliqués dans la synthèse de lipide; SREBP-1c, SCD-1, ChREBP, et ACC dans le foie a augmenté après le retrait des œstrogènes, tandis qu’une diminution (P < 0.01) des niveaux d'ARNm de PPAR-α a été observée. De plus, l'expression hépatique des gènes des cytokines pro-inflammatoires incluant IKKβ, IL-6 ainsi que le contenu protéinique de NF-кB étaient augmentés (P < 0.01) chez les rates Ovx par rapport aux rates ayant subi une Ovx simulée (Sham). Toutes ces perturbations ont été améliorées avec la supplémentation en œstrogènes seulement, ainsi qu'avec l'entraînement en endurance seulement. Dans l'ensemble, nos résultats indiquent que l'exercice physique (en résistance ou en endurance) a un impact significatif sur la réduction de l'accumulation des lipides dans le foie et dans le tissu adipeux des rates Ovx. De plus, chez les rates Ovx, l’entraînement en endurance mimerait les effets des œstrogènes sur l'expression des gènes impliqués dans l'accumulation de lipides et l’inflammation préclinique dans le foie.

Activation of c-Jun N-terminal kinases and p38-mitogen-activated protein kinases in human heart failure secondary to ischaemic heart disease.

Three well-characterized mitogen-activated protein kinase (MAPK) subfamilies are expressed in rodent and rabbit hearts, and are activated by pathophysiological stimuli. We have determined and compared the expression and activation of these MAPKs in donor and failing human hearts. The amount and activation of MAPKs was assessed in samples from the left ventricles of 4 unused donor hearts and 12 explanted hearts from patients with heart failure secondary to ischaemic heart disease. Total MAPKs or dually phosphorylated (activated) MAPKs were detected by Western blotting and MAPK activities were measured by in gel kinase assays. As in rat heart, c-Jun N-terminal kinases (JNKs) were detected in human hearts as bands corresponding to 46 and 54 kDa; p38-MAPK(s) was detected as a band corresponding to approximately 40 kDa, and extracellularly regulated kinases, ERK1 and ERK2, were detected as 44- and 42-kDa bands respectively. The total amounts of 54 kDa JNK, p38-MAPK and ERK2 were similar in all samples, although 46-kDa JNK was reduced in the failing hearts. However, the mean activities of JNKs and p38-MAPK(s) were significantly higher in failing heart samples than in those from donor hearts (P<0.05). There was no significant difference in phosphorylated (activated) ERKs between the two groups. In conclusion, JNKs, p38-MAPK(s) and ERKs are expressed in the human heart and the activities of JNKs and p38-MAPK(s) were increased in heart failure secondary to ischaemic heart disease. These data indicate that JNKs and p38-MAPKs may be important in human cardiac pathology.

Effects of exercise training on autonomic dysfunction management in an experimental model of menopause and myocardial infarction

Objective: The aim of this study was to investigate the effects of exercise training on cardiovascular autonomic dysfunction in ovariectomized rats submitted to myocardial infarction. Methods: Female Wistar rats were divided into the following ovariectomized groups: sedentary ovariectomized (SO), trained ovariectomized (TO), sedentary ovariectomized infarcted (SOI), and trained ovariectomized infarcted (TOI). Trained groups were submitted to an exercise training protocol on a treadmill (8 wk). Arterial baroreflex sensitivity was evaluated by heart rate responses to arterial pressure changes, and cardiopulmonary baroreflex sensitivity was tested by bradycardic and hypotension responses to serotonin injection. Vagal and sympathetic effects were calculated by pharmacological blockade. Results: Arterial pressure was reduced in the TO in comparison with the SO group and increased in the TOI in relation to the SOI group. Exercise training improved the baroreflex sensitivity in both the TO and TOI groups. The TOI group displayed improvement in cardiopulmonary reflex sensitivity compared with the SOI group at the 16 mu g/kg serotonin dose. Exercise training enhanced the vagal effect in both the TO (45%) and TOI (46%) animals compared with the SO and SOI animals and reduced the sympathetic effect in the TOI (38%) in comparison with the SOI animals. Significant correlations were obtained between bradycardic baroreflex responses and vagal (r = -0.7, P < 0.005) and sympathetic (r = 0.7, P < 0.001) effects. Conclusions: These results indicate that exercise training in ovariectomized rats submitted to myocardial infarction improves resting hemodynamic status and reflex control of the circulation, which may be due to an increase in the vagal component. This suggests a homeostatic role for exercise training in reducing the autonomic impairment of myocardial infarction in postmenopausal women.

Is gender crucial for cardiovascular adjustments induced by exercise training in female spontaneously hypertensive rats?

Evidence of mild hypertension in women and female rats and our preliminary observation showing that training is not effective to reduce pressure in female as it does in male spontaneously hypertensive rats (SHR) prompt us to investigate the effects of gender on hemodynamic pattern and microcirculatory changes induced by exercise training. Female SHR and normotensive controls (Wistar- Kyoto rats) were submitted to training (55% VO2 peak; 3 months) or kept sedentary and instrumented for pressure and hindlimb flow measurements at rest and during exercise. Heart, kidney, and skeletal muscles (locomotor/ nonlocomotor) were processed for morphometric analysis of arterioles, capillaries, and venules. High pressure in female SHR was accompanied by an increased arteriolar wall: lumen ratio in the kidney (+30%; P < 0.01) but an unchanged ratio in the skeletal muscles and myocardium. Female SHR submitted to training did not exhibit further changes on the arteriolar wall: lumen ratio and pressure, showing additionally increased hindlimb resistance at rest (+29%; P < 0.05). On the other hand, female SHR submitted to training exhibited increased capillary and venular densities in locomotor muscles (+50% and 2.3- fold versus sedentary SHR, respectively) and normalized hindlimb flow during exercise hyperemia. Left ventricle pressure and weight were higher in SHR versus WKY rats, but heart performance (positive dP/dt(max) and negative dP/dt(max)) was not changed by hypertension or training, suggesting a compensated heart function in female SHR. In conclusion, the absence of training- induced structural changes on skeletal muscle and myocardium arterioles differed from changes observed previously in male SHR, suggesting a gender effect. This effect might contribute to the lack of pressure fall in trained female SHRs.

Brainstem oxytocinergic modulation of heart rate control in rats: effects of hypertension and exercise training

Oxytocinergic brainstem projections participate in the autonomic control of the circulation. We investigated the effects of hypertension and training on cardiovascular parameters after oxytocin (OT) receptor blockade within the nucleus tractus solitarii (NTS) and NTS OT and OT receptor expression. Male spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were trained (55% of maximal exercise capacity) or kept sedentary for 3 months and chronically instrumented (NTS and arterial cannulae). Mean arterial blood pressure (MAP) and heart rate (HR) were measured at rest and during an acute bout of exercise after NTS pretreatment with vehicle or OT antagonist (20 pmol of OT antagonist (200 nl of vehicle)-1). Oxytocin and OT receptor were quantified (35S-oligonucleotide probes, in situ hybridization) in other groups of rats. The SHR exhibited high MAP and HR (P < 0.05). Exercise training improved treadmill performance and reduced basal HR (on average -11%) in both groups, but did not change basal MAP. Blockade of NTS OT receptor increased exercise tachycardia only in trained groups, with a larger effect on trained WKY rats (+31 +/- 9 versus +12 +/- 3 beats min-1 in the trained SHR). Hypertension specifically reduced NTS OT receptor mRNA density (-46% versus sedentary WKY rats, P < 0.05); training did not change OT receptor density, but significantly increased OT mRNA expression (+2.5-fold in trained WKY rats and +15% in trained SHR). Concurrent hypertension- and training-induced plastic (peptide/receptor changes) and functional adjustments (HR changes) of oxytocinergic control support both the elevated basal HR in the SHR group and the slowing of the heart rate (rest and exercise) observed in trained WKY rats and SHR.

Assessment of cognitive function in heart failure patients

Background
Research on the cognitive capacity of heart failure patients is limited, with a paucity of benchmark information available for this population. It is highly likely that cognitive deficits affect patients' understanding of disease and treatment requirements, as well as limiting their functional capacity and ability to implement treatment plans, and undertake self-care.

Aims
The purpose of this study was to establish a comprehensive neurocognitive profile of the heart failure patient through systematic neurocognitive assessment and to determine whether an association existed between severity of heart failure and cognitive abilities.

Methods
Thirty-eight patients were recruited from the heart failure patient databases of two metropolitan hospitals in Melbourne, Australia. Participants were individually assessed using four standardised, internationally recognised neuropsychological tests that examined current and premorbid intelligence, memory and executive functioning.

Results
Although there was no significant decline from premorbid general intellectual function, other specific areas of deficit, including impaired memory and executive functioning, were identified. There were no significant correlations between heart failure severity and the neurocognitive measures used.

Conclusion
The results support the need to recognise cognitive impairment in people with heart failure and to develop an abbreviated method of assessing cognitive function that can be easily implemented in the clinical setting. Identifying cognitive deficits in this population will be useful in guiding the content and nature of treatment plans to maximise adherence and minimise worsening of heart failure symptoms.

Rationale and design of the national benchmarking and evidence-based national clinical guidelines for chronic heart failure management programs study

OBJECTIVES: The National Benchmarks and Evidence-Based National Clinical Guidelines for Heart Failure Management Programs Study is a national, multicenter study designed to determine the nature, range, and effect of interventions applied by chronic heart failure management programs (CHF-MPs) throughout Australia on patient outcomes. Its primary objective is to use these data to develop national benchmarks and evidence-based clinical guidelines and optimize their cost-effective application by reducing quality and outcome variability. DATA SOURCES/STUDY SETTING: Primary data will be collected from CHF-MP coordinators and CHF patients enrolled in these programs on a national basis. Secondary outcome data will be collected from a national morbidity record and from patients' medical records. STUDY DESIGN: Stage I of the study involves a prospective clinical audit of all CHF-MPs throughout Australia (n = 45) to determine the extent of variability in programs currently. Stage II is a prospective cross-sectional survey design enrolling 1,500 patients (average of 40 patients per program) to firstly determine the typical profile of patients being managed via a CHF-MP in Australia and, secondly, the subsequent morbidity and mortality during the 6-month follow-up. Outcome data will be subject to multivariate analysis to determine the key components of care in this regard. All study data will be then examined in the final stage of the study (III) to develop national benchmarks for the application and auditing of CHF-MPs in Australia. CONCLUSION: Variability in patient outcomes is a product of heterogeneity among CHF-MPs. The development of national benchmarks will minimize such heterogeneity and will provide a greater level of evidence for their cost-effective application.

Extent of heart failure self-care as an endpoint to patient education: a literature review

Background: In western countries the number of chronic heart failure (CHF) management programs has escalated in recent times. One key component of them is to teach self-care behaviours that enable affected individuals to monitor themselves and engage in lifestyles that improve their health status.
Aim: The aim of this article is to describe CHF self-care management and to review the literature which examines the effectiveness of patient education on patients’ performance of self-care behaviours.
Design/method: bibliographical databases were searched for papers published in English between 1982 to 2006. The search used the key words: heart failure, education, self-care and measures. Only randomized controlled trials (RCTs) were selected.
Results: Ten randomized controlled trials were selected that used education as an intervention and, in total, 1064 patients with CHF participated in these studies. The studies were heterogenous as to the sample population, the health outcomes measured, the education interventions, the expertise of the educator, and the length of time that was spent on teaching patients. No consistent patterns of implementation and specific evaluation of its impact were found, although three respective groups of investigators reported signifi cant differences in recurrent hospitalisation rates and mortality rates which were relative to usual care.
Conclusions: Teaching patients appropriate CHF self-care behaviours can significantly improve their health outcomes. Improvements in self-care were demonstrated in seven studies but only three had used validated instruments to measure such changes. This suggests that no firm conclusions can be drawn about changes in self-care practices.

Complexity of management and health outcomes in a prospective cohort study of 573 heart failure patients in Australia : does more equal less?

Aims and objectives : To compare the efficacy of chronic heart failure management programmes (CHF-MPs) according to a scoring algorithm used to quantify the level of applied interventions–the Heart Failure Intervention Score (HF-IS).

Background : The overall efficacy of heart failure programmes has been proven in several meta-analyses. However, the debate continues as to which components are essential in a heart failure programme to improve patient outcomes.

Design : Prospective cohort study of patients participating in heart failure programmes.

Method : Forty-eight of 62 (77%) programmes in Australia participating in a national register of CHF-MPs were evaluated using the HF-IS: derived from a summed and weighted score of each intervention applied by the CHF-MP (27 interventions overall). The CHF-MPs were prospectively categorised as relatively low (HF-IS < 190 – n = 39 programmes & 407 patients) or high (HF-IS ≥ 190 – n = 9 programmes & 166 patients) in complexity. Six-month morbidity and mortality rates in 573 consecutively recruited patients with systolic dysfunction and in New York Heart Association Class II–IV were prospectively examined.

Results : Patients exposed to CHF-MPs with a high HF-IS had a lower rate of unplanned, all-cause hospitalisation (n = 24, 14% vs. n = 102, 25%) compared with CHF-MPs with a low HF-IS within six months. On an adjusted basis, CHF-MPs with a high HF-IS were associated with a reduced risk of unplanned hospitalisation and/or death within six months and remained event-free longer.

Conclusion : High complexity CHF-MPs applying more evidence-based interventions are associated with a higher event-free survival over six months.

Relevance to clinical practice : The HF-IS is an easy-to-use evidence-based tool to assist programme coordinators to improve the quality of their heart failure programme which may also improve patient outcomes.

Development of an evidence-based scoring system (HF-IS) to assess the quality of heart failure programmes for patients postdischarge from hospital

Aim.  The aim of this study was to develop a potential scoring algorithm for interventions in a chronic heart failure management programme – the Heart Failure Intervention Score – to facilitate quality improvement and programme auditing.

Background.  The overall efficacy of chronic heart failure management programmes has been demonstrated in several meta-analyses. However, meta-analyses did not determine individual interventions in a programme that resulted in beneficial patient outcomes.

Design.  A prospective cross-sectional survey design.

Method.  All chronic heart failure management programmes in Australia (n = 62), identified by a national register, were surveyed to determine programme characteristics and interventions.

Results.  Of the 62 national chronic heart failure management programmes, 48 (77%) completed the survey and 27 individual interventions were identified. Variability in the use of the key interventions was common among the programmes. Each intervention was given an arbitrary weighted score according to the level of supportive evidence available and a total score calculated. Programmes were then categorised into low or high complexity based on several interventions implemented and their weighted score. A total score of ≥190 (median = 178, interquartile range 176–195) was used to divide programmes into two groups. Nine programmes were categorised into high Heart Failure Intervention Score group and majority of these were based in the acute hospital setting (78%). In the low Heart Failure Intervention Score group, there were 39 programmes of which there were a higher proportion of community-based programmes (38%) and programmes in small community hospitals (10%).

Conclusion.  The Heart Failure Intervention Score provides a potential evidence-based quality improvement tool through which a set of minimum standards can be developed. Implementation of the Heart Failure Intervention Score provides guidance to programme coordinators to enable monitoring of standards of heart failure programmes, which may potentially result in better patient outcomes.