Biomarker Testing and Pre-emptive Therapy in Preventing Heart Failure

In an attempt to reduce the heart failure epidemic,screening and prevention will become an increasing focus ofmanagement in the wider at-risk population. Refining riskprediction through the use of biomarkers in isolation or incombination is emerging as a critical step in this process.The utility of biomarkers to identify disease manifestationsbefore the onset of symptoms and detrimental myocardialdamage is proving to be valuable. In addition, biomarkers thatpredict the likelihood and rate of disease progression over timewill help streamline and focus clinical efforts and therapeuticstrategies. Importantly, several recent early intervention studiesusing biomarker strategies are promising and indicate thatnot only can new-onset heart failure be reduced but also thedevelopment of other cardiovascular conditions.

Predictive Analytics and Decision Support for Heart Failure patients

Thesis (Master's)--University of Washington, 2016-08

Prediction of Sudden Cardiac Arrest for Patients with Congestive Heart Failure

Thesis (Ph.D.)--University of Washington, 2016-07

Body composition changes assessed by bioelectrical impedance and their associations with functional class deterioration in stable heart failure patients

Background: Heart failure (HF) patients develop important changes in body composition, but only a small number of studies have evaluated the associations between these changes and functional class deterioration in a prospective manner. Objective: The aim of this study was to evaluate whether changes in bioimpedance parameters were associated with NYHA functional class deterioration over six months. Methods: A total of 275 chronic stable HF patients confirmed by echocardiography were recruited. Body composition measurements were obtained by whole body bioelectrical impedance with multiple frequency equipment (BodyStat QuadScan 4000). We evaluated functional class using the New York Heart Association (NYHA) classification at baseline and after six months. Results: According to our results, 66 (24%) subjects exhibited functional class deterioration, while 209 improved or exhibited no change. A greater proportion of patients exhibited higher extracellular water (> 5%), and these patients developed hypervolemia, according to location on the resistance/reactance graph. A 5% decrease in resistance/height was associated with functional class deterioration with an OR of 1.42 (95% CI 1.01-2.0, p = 0.04). Conclusions: Body composition assessment through bioelectrical impedance exhibited a valuable performance as a marker of functional class deterioration in stable HF patients.

Cardioprotective effects of Dan-Yang-Fu-Xin decoction on chronic heart failure in rats

Purpose: To evaluate the cardioprotective effects and possible mechanisms of Dan-Yang-Fu-Xin decoction (DYFX) in a rat chronic heart failure (CHF). Methods: A CHF rat model induced by ligation of the left anterior descending coronary artery was used to investigate the cardioprotective effects of DYFX. After intragastric administration for 8 weeks, several functional cardiac indices, including fractional shortening (FS), ejection fraction (EF), heart rate (HR) and cardiac output (CO) were assessed by ultrasound examination. Subsequently, inflammatory markers, viz, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), myocardial enzymes, namely, lactate dehydrogenase (LDH) and creatine kinase (CK), were also assessed by enzyme-linked immunosorbent assay (ELISA). Results: Intragastric administration of DYFX (200, 400 and 600 mg/kg) significantly reversed the decrease in body weight and increase in cardiac weight (p < 0.05) induced by CHF. Treatment with DYFX also significantly reversed EF, FS, HR, and CO changes in CHF rats. In addition, DYFX inhibited the two inflammatory cytokines (TNF-α and IL-6) and myocardial enzymes (CK and LDH), suggesting that these effects may include the mechanisms of cardioprotectiion involved in attenuation of CHF. Conclusion: DYFX possesses cardioprotective effects involving CHF. The protective mechanisms may include the suppression of expression of inflammatory mediators and myocardial enzymes.

Validation de la reproductibilité d’outils de mesure de la fraction d’éjection du ventricule gauche en médecine nucléaire

La fraction d’éjection du ventricule gauche est un excellent marqueur de la fonction cardiaque. Plusieurs techniques invasives ou non sont utilisées pour son calcul : l’angiographie, l’échocardiographie, la résonnance magnétique nucléaire cardiaque, le scanner cardiaque, la ventriculographie radioisotopique et l’étude de perfusion myocardique en médecine nucléaire. Plus de 40 ans de publications scientifiques encensent la ventriculographie radioisotopique pour sa rapidité d’exécution, sa disponibilité, son faible coût et sa reproductibilité intra-observateur et inter-observateur. La fraction d’éjection du ventricule gauche a été calculée chez 47 patients à deux reprises, par deux technologues, sur deux acquisitions distinctes selon trois méthodes : manuelle, automatique et semi-automatique. Les méthodes automatique et semi-automatique montrent dans l’ensemble une meilleure reproductibilité, une plus petite erreur standard de mesure et une plus petite différence minimale détectable. La méthode manuelle quant à elle fournit un résultat systématiquement et significativement inférieur aux deux autres méthodes. C’est la seule technique qui a montré une différence significative lors de l’analyse intra-observateur. Son erreur standard de mesure est de 40 à 50 % plus importante qu’avec les autres techniques, tout comme l’est sa différence minimale détectable. Bien que les trois méthodes soient d’excellentes techniques reproductibles pour l’évaluation de la fraction d’éjection du ventricule gauche, les estimations de la fiabilité des méthodes automatique et semi-automatique sont supérieures à celles de la méthode manuelle.

Validation de la reproductibilité d’outils de mesure de la fraction d’éjection du ventricule gauche en médecine nucléaire

La fraction d’éjection du ventricule gauche est un excellent marqueur de la fonction cardiaque. Plusieurs techniques invasives ou non sont utilisées pour son calcul : l’angiographie, l’échocardiographie, la résonnance magnétique nucléaire cardiaque, le scanner cardiaque, la ventriculographie radioisotopique et l’étude de perfusion myocardique en médecine nucléaire. Plus de 40 ans de publications scientifiques encensent la ventriculographie radioisotopique pour sa rapidité d’exécution, sa disponibilité, son faible coût et sa reproductibilité intra-observateur et inter-observateur. La fraction d’éjection du ventricule gauche a été calculée chez 47 patients à deux reprises, par deux technologues, sur deux acquisitions distinctes selon trois méthodes : manuelle, automatique et semi-automatique. Les méthodes automatique et semi-automatique montrent dans l’ensemble une meilleure reproductibilité, une plus petite erreur standard de mesure et une plus petite différence minimale détectable. La méthode manuelle quant à elle fournit un résultat systématiquement et significativement inférieur aux deux autres méthodes. C’est la seule technique qui a montré une différence significative lors de l’analyse intra-observateur. Son erreur standard de mesure est de 40 à 50 % plus importante qu’avec les autres techniques, tout comme l’est sa différence minimale détectable. Bien que les trois méthodes soient d’excellentes techniques reproductibles pour l’évaluation de la fraction d’éjection du ventricule gauche, les estimations de la fiabilité des méthodes automatique et semi-automatique sont supérieures à celles de la méthode manuelle.

What Are Effective Program Characteristics of Self-Management Interventions in Patients With Heart Failure? : An Individual Patient Data Meta-analysis

Background To identify those characteristics of self-management interventions in patients with heart failure (HF) that are effective in influencing health-related quality of life, mortality, and hospitalizations. Methods and Results Randomized trials on self-management interventions conducted between January 1985 and June 2013 were identified and individual patient data were requested for meta-analysis. Generalized mixed effects models and Cox proportional hazard models including frailty terms were used to assess the relation between characteristics of interventions and health-related outcomes. Twenty randomized trials (5624 patients) were included. Longer intervention duration reduced mortality risk (hazard ratio 0.99, 95% confidence interval [CI] 0.97–0.999 per month increase in duration), risk of HF-related hospitalization (hazard ratio 0.98, 95% CI 0.96–0.99), and HF-related hospitalization at 6 months (risk ratio 0.96, 95% CI 0.92–0.995). Although results were not consistent across outcomes, interventions comprising standardized training of interventionists, peer contact, log keeping, or goal-setting skills appeared less effective than interventions without these characteristics. Conclusion No specific program characteristics were consistently associated with better effects of self-management interventions, but longer duration seemed to improve the effect of self-management interventions on several outcomes. Future research using factorial trial designs and process evaluations is needed to understand the working mechanism of specific program characteristics of self-management interventions in HF patients.

Cognitive impairment in heart failure

The clinical syndrome of heart failure is one of the leading causes of hospitalisation and mortality in older adults. Due to ageing of the general population and improved survival from cardiac disease the prevalence of heart failure is rising. Despite the fact that the majority of patients with heart failure are aged over 65 years old, many with multiple co-morbidities, the association between cognitive impairment and heart failure has received relatively little research interest compared to other aspects of cardiac disease. The presence of concomitant cognitive impairment has implications for the management of patients with heart failure in the community. There are many evidence based pharmacological therapies used in heart failure management which obviously rely on patient education regarding compliance. Also central to the treatment of heart failure is patient self-monitoring for signs indicative of clinical deterioration which may prompt them to seek medical assistance or initiate a therapeutic intervention e.g. taking additional diuretic. Adherence and self-management may be jeopardised by cognitive impairment. Formal diagnosis of cognitive impairment requires evidence of abnormalities on neuropsychological testing (typically a result ≥1.5 standard deviation below the age-standardised mean) in at least one cognitive domain. Cognitive impairment is associated with an increased risk of dementia and people with mild cognitive impairment develop dementia at a rate of 10-15% per year, compared with a rate of 1-2% per year in healthy controls.1 Cognitive impairment has been reported in a variety of cardiovascular disorders. It is well documented among patients with hypertension, atrial fibrillation and coronary artery disease, especially after coronary artery bypass grafting. This background is relevant to the study of patients with heart failure as many, if not most, have a history of one or more of these co-morbidities. A systematic review of the literature to date has shown a wide variation in the reported prevalence of cognitive impairment in heart failure. This range in variation probably reflects small study sample sizes, differences in the heart failure populations studied (inpatients versus outpatients), neuropsychological tests employed and threshold values used to define cognitive impairment. The main aim of this study was to identify the prevalence of cognitive impairment in a representative sample of heart failure patients and to examine whether this association was due to heart failure per se rather than the common cardiovascular co-morbidities that often accompany it such as atherosclerosis and atrial fibrillation. Of the 817 potential participants screened, 344 were included in this study. The study cohort included 196 patients with HF, 61 patients with ischaemic heart disease and no HF and 87 healthy control participants. The HF cohort consisted of 70 patients with HF and coronary artery disease in sinus rhythm, 51 patients with no coronary artery disease in sinus rhythm and 75 patients with HF and atrial fibrillation. All patients with HF had evidence of HF-REF with a LVEF <45% on transthoracic echocardiography. The majority of the cohort was male and elderly. HF patients with AF were more likely to have multiple co-morbidities. Patients recruited from cardiac rehabilitation clinics had proven coronary artery disease, no clinical HF and a LVEF >55%. The ischaemic heart disease group were relatively well matched to healthy controls who had no previous diagnosis of any chronic illness, prescribed no regular medication and also had a LVEF >55%. All participants underwent the same baseline investigations and there were no obvious differences in baseline demographics between each of the cohorts. All 344 participants attended for 2 study visits. Baseline investigations including physiological measurements, electrocardiography, echocardiography and laboratory testing were all completed at the initial screening visit. Participants were then invited to attend their second study visit within 10 days of the screening visit. 342 participants completed all neuropsychological assessments (2 participants failed to complete 1 questionnaire). A full comprehensive battery of neuropsychological assessment tools were administered in the 90 minute study visit. These included three global cognitive screening assessment tools (mini mental state examination, Montreal cognitive assessment tool and the repeatable battery for the assessment of neuropsychological status) and additional measures of executive function (an area we believe has been understudied to date). In total there were 9 cognitive tests performed. These were generally well tolerated. Data were also collected using quality of life questionnaires and health status measures. In addition to this, carers of the study participant were asked to complete a measure of caregiver strain and an informant questionnaire on cognitive decline. The prevalence of cognitive impairment varied significantly depending on the neuropsychological assessment tool used and cut-off value used to define cognitive impairment. Despite this, all assessment tools showed the same pattern of results with those patients with heart failure and atrial fibrillation having poorer cognitive performance than those with heart failure in sinus rhythm. Cognitive impairment was also more common in patients with cardiac disease (either coronary artery disease or heart failure) than age-, sex- and education-matched healthy controls, even after adjustment for common vascular risk factors.

Self-care in Patients with Heart Failure

Objectives: To adapt for the Portuguese language the Self-Care of Heart Failure Index V6.2, analyse the self-care in maintenance, management skills and self-confidence of patients with heart failure who attend the nursing consultation of two Hospitals. Method: Explo- ratory study, sample 110 patients who frequented the nursing consultation for patients with heart failure of two Portuguese hospitals, conducted in the period of 6 months. He appea- led to the descriptive statistics and psychometric tests. Results: Internal consistency similar to the original scale. Mostly elderly, low literacy patients in self-care, low values associated with physical activity to the control of salt in meals taken away from home and inadequate control of signs and symptoms. Conclusion: Patients’ present difficulties in maintenance and management of the disease are self-confident face anyway. This instrument allows for individualized assessment leading to decision-making and action adjusted.

In Vitro Evaluation of Ventricular Cannulation for Rotodynamic Cardiac Assist Devices

The influence of positioning and geometry of ventricular cannulas for contemporary continuous flow Left Ventricular Assist Devices (LVADs) was evaluated in a non-beating isolated heart preparation with borescopic visualization. Preload and LVAD flow were varied to evaluate degrees of ventricular decompression up to the point of ventricular collapse. The performance of a flanged cannula was compared to a conventional bevel-tipped cannula: quantitatively by the maximal flow attainable, and qualitatively by visualization of fluid tracer particles within the ventricular chamber. Three forms of ventricular suck-down occurred: concentric collapse, gradual entrainment and instantaneous entrainment. In some circumstances, unstable oscillations of the ventricle were observed prior to complete collapse. Under conditions of low preload, the flanged cannula demonstrated less positional sensitivity, provided greater flow, and exhibited fewer areas of stagnation than the beveled cannula. These observations warrant further consideration of a flanged ventricular cannula to mitigate complications encountered with conventional cannulae.

Assessment of a New Experimental Model of Isolated Right Ventricular Failure

We assessed a new experimental model of isolated right ventricular (RV) failure, achieved by means of intramyocardial injection of ethanol. RV dysfunction was induced in 13 mongrel dogs via multiple injections of 96% ethanol (total dose 1 mL/kg), all over the inlet and trabecular RV free walls. Hemodynamic and metabolic parameters were evaluated at baseline, after ethanol injection, and on the 14th postoperative day (POD). Echocardiographic parameters were evaluated at baseline, on the sixth POD, and on the 13th POD. The animals were then euthanized for histopathological analysis of the hearts. There was a 15.4% mortality rate. We noticed a decrease in pulmonary blood flow right after RV failure (P = 0.0018), as well as during reoperation on the 14th POD (P = 0.002). The induced RV dysfunction caused an increase in venous lactate levels immediately after ethanol injection and on the 14th POD (P < 0.0003). The echocardiogram revealed a decrease in the RV ejection fraction on the sixth and 13th PODs (P = 0.0001). There was an increased RV end-diastolic volume on the sixth (P = 0.0001) and 13th PODs (P = 0.0084). The right ventricle showed a 74% +/- 0.06% transmural infarction area, with necrotic lesions aged 14 days. Intramyocardial ethanol injection has allowed the creation of a reproducible and inexpensive model of RV failure. The hemodynamic, metabolic, and echocardiographic parameters assessed at different protocol times are compatible with severe RV failure. This model may be useful in understanding the pathophysiology of isolated right-sided heart failure, as well as in the assessment of ventricular assist devices.

Abnormalities in arterial-ventricular coupling in older healthy persons are attenuated by sodium nitroprusside

Chantler PD, Nussbacher A, Gerstenblith G, Schulman SP, Becker LC, Ferrucci L, Fleg JL, Lakatta EG, Najjar SS. Abnormalities in arterial-ventricular coupling in older healthy persons are attenuated by sodium nitroprusside. Am J Physiol Heart Circ Physiol 300: H1914-H1922, 2011. First published March 4, 2011; doi:10.1152/ajpheart.01048.2010.-The coupling between arterial elastance (E(A); net afterload) and lea ventricular elastance (E(LV); pump performance), known as E(A)/E(LV), is a key determinant of cardiovascular performance and shifts during exercise due to a greater increase in E(LV) versus E(A). This normal exercise-induced reduction in E(A)/E(LV) decreases with advancing age. We hypothesized that sodium. nitroprusside (SNP) can acutely ameliorate the age-associated deficits in E(A)/E(LV). At rest and during graded exercise to exhaustion, EA was characterized as end-systolic pressure/stroke volume and E(LV) as end-systolic pressure/end-systolic volume. Resting E(A)/E(LV): did not differ between old (70 +/- 8 yr. n = 15) and young (30 +/- 5 yr. n = 17) subjects because of a tandem increase in E(A) and E(LV) in older subjects. During peak exercise, a blunted increase in E(LV) in old (7.8 +/- 3.1 mmHg/ml) versus young (11.4 +/- 6.5 mmHg/ml) subjects blunted the normal exercise-induced decline in E(A)/E(LV) in old (0.25 +/- 0.11) versus young (0.16 +/- 0.05) subjects. SNP administration to older subjects lowered resting E(A)/E(LV) by 31% via a reduction E(A) (10%) and an increase in E(LV) (47%) and lowered peak exercise E(A)/E(LV) (36%) via an increase in E(LV) (68%) without a change in E(A). Importantly, SNP attenuated the age-associated deficits in E(A)/E(LV) and E(LV) during exercise, and at peak exercise E(A)/E(LV) in older subjects on drug administration did not differ from young subjects without drug administration. In conclusion, some age-associated deficiencies in E(A)/E(LV), E(A), and E(LV), in older subjects can be acutely abolished by SNP infusion. This is relevant to common conditions in older subjects associated with a significant impairment of exercise performance such as frailty or heart failure with preserved ejection fraction.

Dynamic modelling and analysis of hydraulic forces in radial blood pumps

Dissertação de mestrado integrado em Biomedical Engineering Biomaterials, Biomechanics and Rehabilitation

Cardiopulmonary support and extracorporeal membrane oxygenation for cardiac assist.

BACKGROUND: Use of cardiopulmonary bypass for emergency resuscitation is not new. In fact, John Gibbon proposed this concept for the treatment of severe pulmonary embolism in 1937. Significant progress has been made since, and two main concepts for cardiac assist based on cardiopulmonary bypass have emerged: cardiopulmonary support (CPS) and extracorporeal membrane oxygenation (ECMO). The objective of this review is to summarize the state of the art in these two technologies. METHODS: Configuration of CPS is now fairly standard. A mobile cart with relatively large wheels allowing for easy transportation carries a centrifugal pump, a back-up battery with a charger, an oxygen cylinder, and a small heating system. Percutaneous cannulation, pump-driven venous return, rapid availability, and transportability are the main characteristics of a CPS system. Cardiocirculatory arrest is a major predictor of mortality despite the use of CPS. In contrast, CPS appears to be a powerful tool for patients in cardiogenic shock before cardiocirculatory arrest, requiring some type of therapeutic procedures, especially repair of anatomically correctable problems or bridging to other mechanical circulatory support systems such as ventricular assist devices. CPS is in general not suitable for long-term applications because of the small-bore cannulas, resulting in significant pressure gradients and eventually hemolysis. RESULTS: In contrast, ECMO can be designed for longer-term circulatory support. This requires large-bore cannulas and specifically designed oxygenators. The latter are either plasma leakage resistent (true membranes) or relatively thrombo-resistant (heparin coated). Both technologies require oxygenator changeovers although the main reason for this is different (clotting for the former, plasma leakage for the latter). Likewise, the tubing within a roller pump has to be displaced and centrifugal pump heads have to be replaced over time. ECMO is certainly the first choice for a circulatory support system in the neonatal and pediatric age groups, where the other assist systems are too bulky. ECMO is also indicated for patients improving on CPS. Septic conditions are, in general, considered as contraindications for ECMO. CONCLUSIONS: Ease of availability and moderate cost of cardiopulmonary bypass-based cardiac support technologies have to be balanced against the significant immobilization of human resources, which is required to make them successful.