A prospective pilot study evaluating the ‘cardiac decompensation score’ in the setting of intraaortic balloon counterpulsation

The study objective was to determine whether the ‘cardiac decompensation score’ could identify cardiac decompensation in a patient with existing cardiac compromise managed with intraaortic balloon counterpulsation (IABP). A one-group, posttest-only design was utilised to collect observations in 2003 from IABP recipients treated in the intensive care unit of a 450 bed Australian, government funded, public, cardiothoracic, tertiary referral hospital. Twenty-three consecutive IABP recipients were enrolled, four of whom died in ICU (17.4%). All non-survivors exhibited primarily rising scores over the observation period (p < 0.001) and had final scores of 25 or higher. In contrast, the maximum score obtained by a survivor at any time was 15. Regardless of survival, scores for the 23 participants were generally decreasing immediately following therapy escalation (p = 0.016). Further reflecting these changes in patient support, there was also a trend for scores to move from rising to falling at such treatment escalations (p = 0.024). This pilot study indicates the ‘cardiac decompensation score’ to accurately represent changes in heart function specific to an individual patient. Use of the score in conjunction with IABP may lead to earlier identification of changes occurring in a patient's cardiac function and thus facilitate improved IABP outcomes.

Chronic activation of the low affinity site of β1-adrenoceptors stimulates haemodynamics but exacerbates pressure-overload cardiac remodelling

Background and Purpose The β1-adrenoceptor has at least two binding sites, high and low affinity sites (β1H and β1L, respectively), which mediate cardiostimulation. While β1H-adrenoceptor can be blocked by all clinically used β-blockers, β1L-adrenoceptor is relatively resistant to blockade. Thus, chronic β1L-adrenoceptor activation may mediate persistent cardiostimulation, despite the concurrent blockade of β1H-adrenoceptors. Hence, it is important to determine the potential significance of β1L-adrenoceptors in vivo, particularly in pathological situations. Experimental Approach C57Bl/6 male mice were used. Chronic (4 or 8 weeks) β1L-adrenoceptor activation was achieved by treatment, via osmotic mini pumps, with (-)-CGP12177 (10 mg·kg−1·day−1). Cardiac function was assessed by echocardiography and micromanometry. Key Results (-)-CGP12177 treatment of healthy mice increased heart rate and left ventricular (LV) contractility. (-)-CGP12177 treatment of mice subjected to transverse aorta constriction (TAC), during weeks 4–8 or 4–12 after TAC, led to a positive inotropic effect and exacerbated fibrogenic signalling while cardiac hypertrophy tended to be more severe. (-)-CGP12177 treatment of mice with TAC also exacerbated the myocardial expression of hypertrophic, fibrogenic and inflammatory genes compared to untreated TAC mice. Washout of (-)-CGP12177 revealed a more pronounced cardiac dysfunction after 12 weeks of TAC. Conclusions and Implications β1L-adrenoceptor activation provides functional support to the heart, in both normal and pathological (pressure overload) situations. Sustained β1L-adrenoceptor activation in the diseased heart exacerbates LV remodelling and therefore may promote disease progression from compensatory hypertrophy to heart failure.

P2 purinergic receptor mRNA in rat and human sinoatrial node and other heart regions.

It is known that adenosine 5'-triphosphate (ATP) is a cotransmitter in the heart. Additionally, ATP is released from ischemic and hypoxic myocytes. Therefore, cardiac-derived sources of ATP have the potential to modify cardiac function. ATP activates P2X(1-7) and P2Y(1-14) receptors; however, the presence of P2X and P2Y receptor subtypes in strategic cardiac locations such as the sinoatrial node has not been determined. An understanding of P2X and P2Y receptor localization would facilitate investigation of purine receptor function in the heart. Therefore, we used quantitative PCR and in situ hybridization to measure the expression of mRNA of all known purine receptors in rat left ventricle, right atrium and sinoatrial node (SAN), and human right atrium and SAN. Expression of mRNA for all the cloned P2 receptors was observed in the ventricles, atria, and SAN of the rat. However, their abundance varied in different regions of the heart. P2X(5) was the most abundant of the P2X receptors in all three regions of the rat heart. In rat left ventricle, P2Y(1), P2Y(2), and P2Y(14) mRNA levels were highest for P2Y receptors, while in right atrium and SAN, P2Y(2) and P2Y(14) levels were highest, respectively. We extended these studies to investigate P2X(4) receptor mRNA in heart from rats with coronary artery ligation-induced heart failure. P2X(4) receptor mRNA was upregulated by 93% in SAN (P < 0.05), while a trend towards an increase was also observed in the right atrium and left ventricle (not significant). Thus, P2X(4)-mediated effects might be modulated in heart failure. mRNA for P2X(4-7) and P2Y(1,2,4,6,12-14), but not P2X(2,3) and P2Y(11), was detected in human right atrium and SAN. In addition, mRNA for P2X(1) was detected in human SAN but not human right atrium. In human right atrium and SAN, P2X(4) and P2X(7) mRNA was the highest for P2X receptors. P2Y(1) and P2Y(2) mRNA were the most abundant for P2Y receptors in the right atrium, while P2Y(1), P2Y(2), and P2Y(14) were the most abundant P2Y receptor subtypes in human SAN. This study shows a widespread distribution of P2 receptor mRNA in rat heart tissues but a more restricted presence and distribution of P2 receptor mRNA in human atrium and SAN. This study provides further direction for the elucidation of P2 receptor modulation of heart rate and contractility.

Role of low affinity beta1-adrenergic receptors in normal and diseased hearts

ROLE OF LOW AFFINITY β1-ADRENERGIC RECEPTOR IN NORMAL AND DISEASED HEARTS Background: The β1-adrenergic receptor (AR) has at least two binding sites, 1HAR and 1LAR (high and low affinity site of the 1AR respectively) which cause cardiostimulation. Some β-blockers, for example (-)-pindolol and (-)-CGP 12177 can activate β1LAR at higher concentrations than those required to block β1HAR. While β1HAR can be blocked by all clinically used β-blockers, β1LAR is relatively resistant to blockade. Thus, chronic β1LAR activation may occur in the setting of β-blocker therapy, thereby mediating persistent βAR signaling. Thus, it is important to determine the potential significance of β1LAR in vivo, particularly in disease settings. Method and result: C57Bl/6 male mice were used. Chronic (4 weeks) β1LAR activation was achieved by treatment with (-)-CGP12177 via osmotic minipump. Cardiac function was assessed by echocardiography and catheterization. (-)-CGP12177 treatment in healthy mice increased heart rate and left ventricular (LV) contractility without detectable LV remodelling or hypertrophy. In mice subjected to an 8-week period of aorta banding, (-)-CGP12177 treatment given during 4-8 weeks led to a positive inotropic effect. (-)-CGP12177 treatment exacerbated LV remodelling indicated by a worsening of LV hypertrophy by ??% (estimated by weight, wall thickness, cardiomyocyte size) and interstitial/perivascular fibrosis (by histology). Importantly, (-)-CGP12177 treatment to aorta banded mice exacerbated cardiac expression of hypertrophic, fibrogenic and inflammatory genes (all p<0.05 vs. non-treated control with aorta banding).. Conclusion: β1LAR activation provides functional support to the heart, in both normal and diseased (pressure overload) settings. Sustained β1LAR activation in the diseased heart exacerbates LV remodelling and therefore may promote disease progression from compensatory hypertrophy to heart failure. Word count: 270

The role of cardiopulmonary signals in the dynamics of the eye's wavefront aberrations

Abstract—The role of cardiopulmonary signals in the dynamics of wavefront aberrations in the eye has been examined. Synchronous measurement of the eye’s wavefront aberrations, cardiac function, blood pulse, and respiration signals were taken for a group of young, healthy subjects. Two focusing stimuli, three breathing patterns, as well as natural and cycloplegic eye conditions were examined. A set of tools, including time–frequency coherence and its metrics, has been proposed to acquire a detailed picture of the interactions of the cardiopulmonary system with the eye’s wavefront aberrations. The results showed that the coherence of the blood pulse and its harmonics with the eye’s aberrations was, on average, weak (0.4 ± 0.15), while the coherence of the respiration signal with eye’s aberrations was, on average, moderate (0.53 ± 0.14). It was also revealed that there were significant intervals during which high coherence occurred. On average, the coherence was high (>0.75) during 16% of the recorded time, for the blood pulse, and 34% of the time for the respiration signal. A statistically significant decrease in average coherence was noted for the eye’s aberrations with respiration in the case of fast controlled breathing (0.5 Hz). The coherence between the blood pulse and the defocus was significantly larger for the far target than for the near target condition. After cycloplegia, the coherence of defocus with the blood pulse significantly decreased, while this was not the case for the other aberrations. There was also a noticeable, but not statistically significant, increase in the coherence of the comatic term and respiration in that case. By using nonstationary measures of signal coherence, a more detailed picture of interactions between the cardiopulmonary signals and eye’s wavefront aberrations has emerged.

MRI-based strain and strain rate analysis of left ventricle: A modified hierarchical transformation model

Background Different from other indicators of cardiac function, such as ejection fraction and transmitral early diastolic velocity, myocardial strain is promising to capture subtle alterations that result from early diseases of the myocardium. In order to extract the left ventricle (LV) myocardial strain and strain rate from cardiac cine-MRI, a modified hierarchical transformation model was proposed. Methods A hierarchical transformation model including the global and local LV deformations was employed to analyze the strain and strain rate of the left ventricle by cine-MRI image registration. The endocardial and epicardial contour information was introduced to enhance the registration accuracy by combining the original hierarchical algorithm with an Iterative Closest Points using Invariant Features algorithm. The hierarchical model was validated by a normal volunteer first and then applied to two clinical cases (i.e., the normal volunteer and a diabetic patient) to evaluate their respective function. Results Based on the two clinical cases, by comparing the displacement fields of two selected landmarks in the normal volunteer, the proposed method showed a better performance than the original or unmodified model. Meanwhile, the comparison of the radial strain between the volunteer and patient demonstrated their apparent functional difference. Conclusions The present method could be used to estimate the LV myocardial strain and strain rate during a cardiac cycle and thus to quantify the analysis of the LV motion function.

Molecular architecture of the human sinus node: insights into the function of the cardiac pacemaker.

BACKGROUND: Although we know much about the molecular makeup of the sinus node (SN) in small mammals, little is known about it in humans. The aims of the present study were to investigate the expression of ion channels in the human SN and to use the data to predict electrical activity. METHODS AND RESULTS: Quantitative polymerase chain reaction, in situ hybridization, and immunofluorescence were used to analyze 6 human tissue samples. Messenger RNA (mRNA) for 120 ion channels (and some related proteins) was measured in the SN, a novel paranodal area, and the right atrium (RA). The results showed, for example, that in the SN compared with the RA, there was a lower expression of Na(v)1.5, K(v)4.3, K(v)1.5, ERG, K(ir)2.1, K(ir)6.2, RyR2, SERCA2a, Cx40, and Cx43 mRNAs but a higher expression of Ca(v)1.3, Ca(v)3.1, HCN1, and HCN4 mRNAs. The expression pattern of many ion channels in the paranodal area was intermediate between that of the SN and RA; however, compared with the SN and RA, the paranodal area showed greater expression of K(v)4.2, K(ir)6.1, TASK1, SK2, and MiRP2. Expression of ion channel proteins was in agreement with expression of the corresponding mRNAs. The levels of mRNA in the SN, as a percentage of those in the RA, were used to estimate conductances of key ionic currents as a percentage of those in a mathematical model of human atrial action potential. The resulting SN model successfully produced pacemaking. CONCLUSIONS: Ion channels show a complex and heterogeneous pattern of expression in the SN, paranodal area, and RA in humans, and the expression pattern is appropriate to explain pacemaking.

Risk factors for impaired respiratory function during nurse-administered procedural sedation and analgesia in the cardiac catheterisation laboratory : a matched case-control study

Background: Side effects of the medications used for procedural sedation and analgesia in the cardiac catheterisation laboratory are known to cause impaired respiratory function. Impaired respiratory function poses considerable risk to patient safety as it can lead to inadequate oxygenation. Having knowledge about the conditions that predict impaired respiratory function prior to the procedure would enable nurses to identify at-risk patients and selectively implement intensive respiratory monitoring. This would reduce the possibility of inadequate oxygenation occurring. Aim: To identify pre-procedure risk factors for impaired respiratory function during nurse-administered procedural sedation and analgesia in the cardiac catheterisation laboratory. Design: Retrospective matched case–control. Methods: 21 cases of impaired respiratory function were identified and matched to 113 controls from a consecutive cohort of patients over 18 years of age. Conditional logistic regression was used to identify risk factors for impaired respiratory function. Results: With each additional indicator of acute illness, case patients were nearly two times more likely than their controls to experience impaired respiratory function (OR 1.78; 95% CI 1.19–2.67; p = 0.005). Indicators of acute illness included emergency admission, being transferred from a critical care unit for the procedure or requiring respiratory or haemodynamic support in the lead up to the procedure. Conclusion: Several factors that predict the likelihood of impaired respiratory function were identified. The results from this study could be used to inform prospective studies investigating the effectiveness of interventions for impaired respiratory function during nurse-administered procedural sedation and analgesia in the cardiac catheterisation laboratory.

Acute illness is a risk factor for impaired respiratory function during nurse-administered procedural sedation and analgesia in the cardiac catheterization laboratory

Impaired respiratory function (IRF) during procedural sedation and analgesia (PSA) poses considerable risk to patient safety as it can lead to inadequate oxygenation and ventilation. Risk factors that can be screened prior to the procedure have not been identified for the cardiac catheterization laboratory (CCL).

Caveat Anicula! Beware of the Quiet Little Old Ladies : Demographics, Pharmacotherapy, Survival and Readmissions in a 10 Year Cohort of Heart Failure Patients with Preserved Systolic Function

Objective--To determine whether heart failure with preserved systolic function (HFPSF) has different natural history from left ventricular systolic dysfunction (LVSD). Design and setting--A retrospective analysis of 10 years of data (for patients admitted between 1 July 1994 and 30 June 2004, and with a study census date of 30 June 2005) routinely collected as part of clinical practice in a large tertiary referral hospital.Main outcome measures-- Sociodemographic characteristics, diagnostic features, comorbid conditions, pharmacotherapies, readmission rates and survival.Results--Of the 2961 patients admitted with chronic heart failure, 753 had echocardiograms available for this analysis. Of these, 189 (25%) had normal left ventricular size and systolic function. In comparison to patients with LVSD, those with HFPSF were more often female (62.4% v 38.5%; P = 0.001), had less social support, and were more likely to live in nursing homes (17.9% v 7.6%; P < 0.001), and had a greater prevalence of renal impairment (86.7% v 6.2%; P = 0.004), anaemia (34.3% v 6.3%; P = 0.013) and atrial fibrillation (51.3% v 47.1%; P = 0.008), but significantly less ischaemic heart disease (53.4% v 81.2%; P = 0.001). Patients with HFPSF were less likely to be prescribed an angiotensin-converting enzyme inhibitor (61.9% v 72.5%; P = 0.008); carvedilol was used more frequently in LVSD (1.5% v 8.8%; P < 0.001). Readmission rates were higher in the HFPSF group (median, 2 v 1.5 admissions; P = 0.032), particularly for malignancy (4.2% v 1.8%; P < 0.001) and anaemia (3.9% v 2.3%; P < 0.001). Both groups had the same poor survival rate (P = 0.912). Conclusions--Patients with HFPSF were predominantly older women with less social support and higher readmission rates for associated comorbid illnesses. We therefore propose that reduced survival in HFPSF may relate more to comorbid conditions than suboptimal cardiac management.

Respiratory monitoring practices during procedural sedation and analgesia in the cardiac catheterisation laboratory could be improved by using capnography to assess ventilation

Background: Procedural sedation and analgesia (PSA) administered by nurses in the cardiac catheterisation laboratory (CCL) is unlikely to yield serious complications. However, the safety of this practice is dependent on timely identification and treatment of depressed respiratory function. Aim: Describe respiratory monitoring in the CCL. Methods: Retrospective medical record audit of adult patients who underwent a procedure in the CCLs of one private hospital in Brisbane during May and June 2010. An electronic database was used to identify subjects and an audit tool ensured data collection was standardised. Results: Nurses administered PSA during 172/473 (37%) procedures including coronary angiographies, percutaneous coronary interventions, electrophysiology studies, radiofrequency ablations, cardiac pacemakers, implantable cardioverter defibrillators, temporary pacing leads and peripheral vascular interventions. Oxygen saturations were recorded during 160/172 (23%) procedures, respiration rate was recorded during 17/172 (10%) procedures, use of oxygen supplementation was recorded during 40/172 (23%) procedures and 13/172 (7.5%; 95% CI=3.59–11.41%) patients experienced oxygen desaturation. Conclusion: Although oxygen saturation was routinely documented, nurses did not regularly record respiration observations. It is likely that surgical draping and the requirement to minimise radiation exposure interfered with nurses’ ability to observe respiration. Capnography could overcome these barriers to respiration assessment as its accurate measurement of exhaled carbon dioxide coupled with the easily interpretable waveform output it produces, which displays a breath-by-breath account of ventilation, enables identification of respiratory depression in real-time. Results of this audit emphasise the need to ascertain the clinical benefits associated with using capnography to assess ventilation during PSA in the CCL.

Nurse-administered procedural sedation and analgesia in the cardiac catheterisation laboratory : a mixed methods study

The cardiac catheterisation laboratory (CCL) is a specialised medical radiology facility where both chronic-stable and life-threatening cardiovascular illness is evaluated and treated. Although there are many potential sources of discomfort and distress associated with procedures performed in the CCL, a general anaesthetic is not usually required. For this reason, an anaesthetist is not routinely assigned to the CCL. Instead, to manage pain, discomfort and anxiety during the procedure, nurses administer a combination of sedative and analgesic medications according to direction from the cardiologist performing the procedure. This practice is referred to as nurse-administered procedural sedation and analgesia (PSA). While anecdotal evidence suggested that nurse-administered PSA was commonly used in the CCL, it was clear from the limited information available that current nurse-led PSA administration and monitoring practices varied and that there was contention around some aspects of practice including the type of medications that were suitable to be used and the depth of sedation that could be safely induced without an anaesthetist present. The overall aim of the program of research presented in this thesis was to establish an evidence base for nurse-led sedation practices in the CCL context. A sequential mixed methods design was used over three phases. The objective of the first phase was to appraise the existing evidence for nurse-administered PSA in the CCL. Two studies were conducted. The first study was an integrative review of empirical research studies and clinical practice guidelines focused on nurse-administered PSA in the CCL as well as in other similar procedural settings. This was the first review to systematically appraise the available evidence supporting the use of nurse-administered PSA in the CCL. A major finding was that, overall, nurse-administered PSA in the CCL was generally deemed to be safe. However, it was concluded from the analysis of the studies and the guidelines that were included in the review, that the management of sedation in the CCL was impacted by a variety of contextual factors including local hospital policy, workforce constraints and cardiologists’ preferences for the type of sedation used. The second study in the first phase was conducted to identify a sedation scale that could be used to monitor level of sedation during nurse-administered PSA in the CCL. It involved a structured literature review and psychometric analysis of scale properties. However, only one scale was found that was developed specifically for the CCL, which had not undergone psychometric testing. Several weaknesses were identified in its item structure. Other sedation scales that were identified were developed for the ICU. Although these scales have demonstrated validity and reliability in the ICU, weaknesses in their item structure precluded their use in the CCL. As findings indicated that no existing sedation scale should be applied to practice in the CCL, recommendations for the development and psychometric testing of a new sedation scale were developed. The objective of the second phase of the program of research was to explore current practice. Three studies were conducted in this phase using both quantitative and qualitative research methods. The first was a qualitative explorative study of nurses’ perceptions of the issues and challenges associated with nurse-administered PSA in the CCL. Major themes emerged from analysis of the qualitative data regarding the lack of access to anaesthetists, the limitations of sedative medications, the barriers to effective patient monitoring and the impact that the increasing complexity of procedures has on patients' sedation requirements. The second study in Phase Two was a cross-sectional survey of nurse-administered PSA practice in Australian and New Zealand CCLs. This was the first study to quantify the frequency that nurse-administered PSA was used in the CCL setting and to characterise associated nursing practices. It was found that nearly all CCLs utilise nurse-administered PSA (94%). Of note, by characterising nurse-administered PSA in Australian and New Zealand CCLs, several strategies to improve practice, such as setting up protocols for patient monitoring and establishing comprehensive PSA education for CCL nurses, were identified. The third study in Phase Two was a matched case-control study of risk factors for impaired respiratory function during nurse-administered PSA in the CCL setting. Patients with acute illness were found to be nearly twice as likely to experience impaired respiratory function during nurse-administered PSA (OR=1.78; 95%CI=1.19-2.67; p=0.005). These significant findings can now be used to inform prospective studies investigating the effectiveness of interventions for impaired respiratory function during nurse-administered PSA in the CCL. The objective of the third and final phase of the program of research was to develop recommendations for practice. To achieve this objective, a synthesis of findings from the previous phases of the program of research informed a modified Delphi study, which was conducted to develop a set of clinical practice guidelines for nurse-administered PSA in the CCL. The clinical practice guidelines that were developed set current best practice standards for pre-procedural patient assessment and risk screening practices as well as the intra and post-procedural patient monitoring practices that nurses who administer PSA in the CCL should undertake in order to deliver safe, evidence-based and consistent care to the many patients who undergo procedures in this setting. In summary, the mixed methods approach that was used clearly enabled the research objectives to be comprehensively addressed in an informed sequential manner, and, as a consequence, this thesis has generated a substantial amount of new knowledge to inform and support nurse-led sedation practice in the CCL context. However, a limitation of the research to note is that the comprehensive appraisal of the evidence conducted, combined with the guideline development process, highlighted that there were numerous deficiencies in the evidence base. As such, rather than being based on high-level evidence, many of the recommendations for practice were produced by consensus. For this reason, further research is required in order to ascertain which specific practices result in the most optimal patient and health service outcomes. Therefore, along with necessary guideline implementation and evaluation projects, post-doctoral research is planned to follow up on the research gaps identified, which are planned to form part of a continuing program of research in this field.