Fractal analysis of heart rate variability as a predictor of mortality: A systematic review and meta-analysis.

Previous studies have suggested benefits of applying fractal analysis to intervals between R waves in electrocardiography as an additional prognostic marker. The aim of this study was to investigate whether fractal analysis can provide an independent predictor of cardiac mortality or all-cause mortality. Prognostic cohort studies reporting fractal heart rate variability results from 24-h Holter monitor recordings were selected for comparison. Populations were subdivided into four groups-post-myocardial infarction, left ventricular dysfunction, other cardiac, and non-cardiac patients-and analysed using ANOVA, Forest plots (using pooled mean difference), and Funnel plots. The most significant mean differences were recorded in short-term fractal self-similarity (α1) (-0.17, 95% CI [-0.21, -0.13], p < 0.00001) and the traditional measure called standard deviation of NN intervals (SDNN) (-13.31, 95% CI [-18.89, -7.73], p < 0.00001) between the deceased and survivor groups. Fractal measures of long-term fractal self-similarity (α2), 1/f scaling (ß), and traditional heart rate variability measures of high frequency to low frequency ratio show promise. This review indicated that fractal measure α1 and traditional measure SDNN could be potential predictors of mortality, but require further assessment to determine appropriate thresholds for clinical significance and additional targeted prognostic studies to properly define their applicability as prognostic markers. Therefore, clinicians should interpret fractal and traditional measures with caution since such measures have yet to be fully described as biomarkers for clinical application.

Tolvaptan for Heart Failure in Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Heart failure (HF) is frequently associated with renal impairment. Tolvaptan is reported to be effective in treating congestion in HF without significant electrolyte loss compared to conventional diuretics. However, the safety and efficacy of its use in patients with chronic kidney disease (CKD) is uncertain. This systematic review and meta-analysis evaluated the efficacy and safety outcomes of tolvaptan for HF management in patients with CKD, with a focus at a physiologic basis related to safety. METHODS: We searched for observational studies and randomised clinical trials (RCTs) that assessed the effects of tolvaptan against placebo or standard care in adult patients with HF and CKD. Our protocol was registered with PROSPERO (number CRD42017052775). RESULTS: Seventeen studies were included in the qualitative review and six in the meta-analysis involving 1597 patients. Tolvaptan was associated with an increase in sodium concentration. No significant differences in change of eGFR and serum creatinine were found between tolvaptan and control groups. Urine flow rate appears to increase significantly with tolvaptan compared to baseline (p<0.0001). The meta-analysis demonstrated no heterogeneity between studies but the possibility of publication bias due to incomplete reporting in excluded studies and lack of RCTs. CONCLUSIONS: The safety profile of tolvaptan appears acceptable for patients with HF and CKD. There is evidence for an improvement in serum sodium and reduction in body water without deterioration in renal function. Further research is needed to elucidate the long-term benefits of tolvaptan as an adjunct or alternative to diuretics in such patients.

Symptom-to-Balloon Time is a Strong Predictor of Adverse Events Following Primary Percutaneous Coronary Intervention: Results From the Australian Capital Territory PCI Registry.

BACKGROUND: Notwithstanding improvements in door-to-balloon time, adverse event rates after primary PCI have remained steady. We analysed the effect of symptom-to-balloon (STB) time, a reflection of total ischaemic time, on major adverse cardiovascular events (MACE) and explored predictors of prolonged STB time. METHODS: The study population included 1002 consecutive patients (22.4% women) with a mean age of 62.3±13.2 years, who underwent primary PCI during 2008-2014. Groups were compared for STB ≤ and >240min. Primary endpoint was one-year MACE, a composite of death, reinfarction, stent thrombosis or target vessel revascularisation. RESULTS: Symptom-to-balloon time was available in 893 patients of which 588 (65.8%) had STB ≤240min and 305 (34.2%) had STB >240min. The incidence of one-year MACE increased significantly in a stepwise manner with increasing STB time (p for trend=0.003). Symptom-to-balloon time was an independent predictor of one-year MACE along with age >70 years, final TIMI flow <3, three vessel disease, cardiogenic shock and out-of-hospital cardiac arrest. We also performed a multivariate analysis to determine predictors of delayed treatment. Predictors of STB time >240min were age >70 years, female gender, diabetes, absence of prehospital catheter laboratory activation and presentation to a non-PCI centre. CONCLUSION: Incidence of MACE was strongly correlated with STB time and STB time was an independent predictor of MACE. We have identified specific subgroups with prolonged STB times (age >70, female gender, diabetes, absence of prehospital activation and presentation to a non-PCI centre). This information should inform future studies and strategies to minimise delays in these subgroups for improved outcomes.

Multiple biomarkers including cardiac troponins T and I measured by high-sensitivity assays, as predictors of long-term mortality in patients with chronic renal failure who underwent dialysis.

There is a high cardiac mortality in patients on long-term renal dialysis. No studies have reported long-term outcomes relating to both high-sensitivity cardiac troponin T (hs-cTnT) and high-sensitivity cardiac troponin I (hs-cTnI) in these patients. Patients who underwent long-term dialysis at the Canberra Hospital had blood samples collected for both cardiac and other biomarkers. Samples were stored at -80°C until analysis. Mortality data were collected at 5 years, and univariate and multivariate analyses were performed to identify which biomarkers were predictive of mortality at 5 years. After multivariate analysis, albumin, C-reactive protein (CRP), and hs-cTnT remained independently predictive of all-cause mortality, with hs-cTnT having the highest hazard ratio. If hs-cTnT was excluded from the analysis, then hs-cTnI was independently predictive of mortality. For hs-cTnT, for both genders, the ninety-ninth percentile, derived from a population with subjects with subclinical disease excluded, served as an excellent partition between survivors and nonsurvivors. Receiver-operating characteristic curve analysis for hs-cTnT had area under the curve of 0.798 and for hs-cTnI of 0.774. Kaplan-Meier curves for the aggregation of albumin, CRP, and hs-cTnT showed a stronger predictive power with receiver-operating characteristic area under the curve of 0.805. The addition of echocardiographic data in an analysis of all patients who had an echocardiogram for clinical reasons (n = 105) did not alter the final observations in this subgroup. In conclusion, hs-cTnT retains a superior predictive power in a dialysis-dependent population for identifying those at risk for death and when aggregated with albumin and CRP also has substantial additive value for identifying mortality risk in a renal-dialysis population.

Shorter ischaemic time and improved survival with pre-hospital STEMI diagnosis and direct transfer for primary PCI.

BACKGROUND: We sought to determine if our regional program for pre-hospital STEMI diagnosis and direct transfer for primary PCI (PPCI) was associated with shorter ischaemic times and improved survival compared with ED diagnosis. METHODS: STEMI diagnosis was made at the scene by pre-hospital ECG or in local EDs depending on patient presentation. Ambulance ECGs were transmitted to our ED for cath lab activation. Patient variables and outcomes at 12 months were recorded. RESULTS: We treated 782 consecutive patients with PPCI during January 2008-June 2013. Cath lab activation was initiated prior to hospital arrival (pre-hospital) in 24% of cases and by ED in 76% of cases. Median total ischaemic time was 154 min for pre-hospital and 211 minutes for ED patients (p<0.0001). Mortality at 12 months was 7.9% in the ED group compared with 3.7% in the pre-hospital group (p=0.036). On multivariate Cox regression analysis including baseline and procedural variables, pre-hospital activation remained an independent predictor of mortality (HR 0.45, 95% CI 0.20-1.0, p=0.03). CONCLUSIONS: Pre-hospital diagnosis of STEMI and direct transfer to the cath lab reduced total ischaemic time by 57 minutes and mortality by >50% following PPCI. Further efforts are needed to increase the proportion of STEMI patients treated using this strategy.

Over time, high-sensitivity TnT replaces NT-proBNP as the most powerful predictor of death in patients with dialysis-dependent chronic renal failure.

BACKGROUND: Cardiac biomarkers are emerging as a potentially powerful prognostic tool for renal-dialysis patients. The optimal biomarker and/or combination of biomarkers for predicting mortality remain uncertain. This study evaluates the prognostic value of the new high-sensitivity troponin T (TnT) assay compared to established biomarkers. METHODS: All patients had blood sampled for prospective assessment of the prognostic value of traditional risk markers including albumin and CRP, and cardiac biomarkers BNP, NT-proBNP, TnT and TnI. Patients were closely monitored clinically. Mortality and morbidity outcomes were documented for a national morbidity and mortality database. Stored samples were subsequently used to measure TnT with a new high-sensitivity assay. RESULTS: After a median of 30 months from blood collection, NT-proBNP was the most powerful predictor of all-cause mortality, along with albumin. After a median of 46.7 months the new high-sensitive TnT assay was the only cardiac biomarker predictive of all-cause mortality. TnT was detectable in all dialysis patients using the high-sensitive TnT assay with a cut-point of 24.15 ng/L below which all patients survived. CONCLUSIONS: The new hs-TnT is the most powerful biomarker for prognostic classification for all-cause mortality of all the commonly used biomarkers for our renal-dialysis population. Our study also suggests that cardiac biomarkers have a different prognostic ability for different time frames with NT-proBNP being a better predictor for early mortality and troponin for later mortality.

Newer cardiac troponin I assays have similar performance to troponin T in patients with end-stage renal disease.

BACKGROUND: Troponin T is present in the blood of a majority of patients with endstage renal disease (ESRD) undergoing regular dialysis and presence of troponin T is a predictor of adverse outcome in these patients. With several new formulations of troponin I assays available, this study was performed to see whether these newer assays were able to detect troponin I in these patients more effectively than the older assays. METHODS: One hundred and forty-three patients undergoing regular haemodialysis or peritoneal dialysis had plasma collected and troponin T and troponin I measured by a variety of assays. RESULTS: The newer troponin I assays (Abbott Architect, Bayer Centaur and Beckman Accu-TnI) were able to detect troponin I (>75% of samples) as effectively as the Roche assay was able to detect troponin T, while other troponin I assays had a much lower rate of detection of troponin - DPC Immulite 2000 16% and Abbott AxSYM 35%. However, the troponin T assay had more samples detected at concentrations corresponding to an assay CV of 10% (59% of samples) than did the newer troponin I assays (highest on the Bayer Centaur at 37%). CONCLUSIONS: Newer assays demonstrate that troponin I is present in a similar number of samples as is troponin T, in the blood of patients with dialysis-dependent renal failure, and these newer troponin I assays identify patients at risk of experiencing a cardiac event.

Population-based detection of systolic and diastolic dysfunction with amino-terminal pro-B-type natriuretic peptide.

BACKGROUND: There is limited information regarding the clinical utility of amino-terminal pro-B-type natriuretic peptide (NT-proBNP) for the detection of left ventricular (LV) dysfunction in the community. We evaluated predictors of circulating NT-proBNP levels and determined the utility of NT-proBNP to detect systolic and diastolic LV dysfunction in older adults. METHODS: A population-based sample of 1229 older adults (mean age 69.4 years, 50.1% women) underwent echocardiographic assessment of cardiac structure and function and measurement of circulating NT-proBNP levels. RESULTS: Predictors of NT-proBNP included age, female sex, body mass index, and cardiorenal parameters (diastolic dysfunction [DD] severity; LV mass and left atrial volume; right ventricular overload; decreasing ejection fraction [EF] and creatinine clearance). The performance of NT-proBNP to detect any degree of LV dysfunction, including mild DD, was poor (area under the curve 0.56-0.66). In contrast, the performance of NT-proBNP for the detection of EF < or = 40% and moderate-severe DD was strong with area under the curve of > 0.90 regardless of age and sex; history of hypertension, diabetes, coronary artery disease; or body mass category. The ability of NT-proBNP to detect EF < or = 40% and/or moderate-severe DD was optimized by using age/sex-specific limits. Of "false-positive" tests, 88% (124/141) were explained after considering cardiorenal determinants of NT-proBNP levels. CONCLUSIONS: Amino-terminal pro-B-type natriuretic peptide is a suboptimal marker of mild LV dysfunction, but performs strongly as a marker of EF < or = 40% and/or moderate-severe DD in the community. Most subjects with a positive NT-proBNP test, using age/sex-specific cutoffs, had prognostically significant abnormalities of cardiac structure or function.

Prevalence of heart failure and systolic ventricular dysfunction in older Australians: the Canberra Heart Study.

OBJECTIVE: To estimate the prevalence of heart failure (HF) and left ventricular (LV) systolic dysfunction in a population-based sample of older Australians. DESIGN, SETTING AND PARTICIPANTS: A cross-sectional survey of 2000 randomly selected residents of Canberra, aged 60-86 years, conducted between February 2002 and June 2003. Participants were assessed by history, physical examination by a cardiologist, and echocardiography. MAIN OUTCOME MEASURES: Age- and sex-specific prevalence rates of clinical HF and LV systolic dysfunction (defined as LV ejection fraction < or = 50%). RESULTS: Of 1846 people eligible for our study, 1388 (75%) agreed to participate and 1275 completed all investigations (mean age, 69.4 years; 50% men). In the study sample, 72 subjects (5.6%; 95% CI, 4.4%-7.1%) had clinical HF that had been previously diagnosed and was confirmed by our assessment. A further 0.6% (95% CI, 0.3%-1.2%) had undiagnosed clinical HF (ie, evidence of structural heart disease and symptoms/signs of cardiac insufficiency without a previous diagnosis of clinical HF). Thus, the overall prevalence of clinical HF in the sample was 6.3% (95% CI, 5.0%-7.7%). Clinical HF increased in prevalence with advancing age (a 4.4-fold increase from the 60-64-years age group to the 80-86-years age group; P < 0.0001). Of the 75 subjects (5.9%; 95% CI, 4.7%-7.3%) with LV systolic dysfunction, 44 (59%) were in the preclinical stage of disease. CONCLUSION: Diagnosed HF cases represent the "tip of the iceberg" for the national burden of HF and LV systolic dysfunction. Clinically identifiable HF cases can remain undiagnosed, and the majority of people with LV systolic dysfunction are in a preclinical stage of the disease.

What motivates senior clinicians to teach medical students?

BACKGROUND: This study was designed to assess the motivations of senior medical clinicians to teach medical students. This understanding could improve the recruitment and retention of important clinical teachers. METHODS: The study group was 101 senior medical clinicians registered on a teaching list for a medical school teaching hospital (The Canberra Hospital, ACT, Australia). Their motivations to teach medical students were assessed applying Q methodology. RESULTS: Of the 75 participants, 18 (24%) were female and 57 (76%) were male. The age distribution was as follows: 30-40 years = 16 participants (21.3%), 41-55 years = 46 participants (61.3%) and > 55 years = 13 participants (17.3%). Most participants (n = 48, 64%) were staff specialists and 27 (36%) were visiting medical officers. Half of the participants were internists (n = 39, 52%), 12 (16%) were surgeons, and 24 (32%) were other sub-specialists. Of the 26 senior clinicians that did not participate, two were women; 15 were visiting medical officers and 11 were staff specialists; 16 were internists, 9 were surgeons and there was one other sub-specialist. The majority of these non-participating clinicians fell in the 41-55 year age group. The participating clinicians were moderately homogenous in their responses. Factor analysis produced 4 factors: one summarising positive motivations for teaching and three capturing impediments for teaching. The main factors influencing motivation to teach medical students were intrinsic issues such as altruism, intellectual satisfaction, personal skills and truth seeking. The reasons for not teaching included no strong involvement in course design, a heavy clinical load or feeling it was a waste of time. CONCLUSION: This study provides some insights into factors that may be utilised in the design of teaching programs that meet teacher motivations and ultimately enhance the effectiveness of the medical teaching workforce.

Acute myocardial infarction associated with albuterol.

OBJECTIVE: To report a case of acute myocardial infarction (AMI) following the use of albuterol (salbutamol) in a patient without preexisting coronary artery disease and to review the related literature. CASE SUMMARY: An 84-year-old white woman with no history of cardiac disease was treated for an exacerbation of chronic obstructive pulmonary disease with albuterol 5 mg and ipratropium bromide 500 microg nebulized with oxygen; the albuterol was given in the same dose every 2 hours. Her respiratory condition improved, but soon after the sixth dose of albuterol, she developed increasing chest tightness. The electrocardiogram (ECG) showed ST segment elevation in the chest leads (V(2,3)) and, subsequently, the troponin I concentration and creatine kinase rose. Urgent coronary angiography showed smooth coronary arteries with no obstructive coronary artery disease or thrombosis. Left ventriculography showed anterior hypokinesia consistent with anterior myocardial injury. A subsequent echocardiogram also revealed normal left ventricular size but anterior, anteroseptal, and apical hypokinesia. An objective causality assessment revealed that albuterol had a probable likelihood of causing the AMI in this patient. DISCUSSION: A MEDLINE search (1966-February 2004) revealed 6 other case reports of AMI associated with albuterol treatment. The possible pathogenesis of albuterol-induced myocardial necrosis includes activation of cardiac and peripheral beta(2)-adrenoceptors, inducing positive chronotropic and inotropic effects and vasodilation with coronary blood flow redistribution. Albuterol can also cause hypokalemia and other metabolic and electrical changes, including prolonged QT interval. These effects may be especially detrimental in patients with hypoxia, hypercapnea, and preexisting heart diseases. CONCLUSIONS: Although myocardial injury is a rare complication following albuterol therapy, clinicians should use high-dose beta(2)-agonists with caution. Close monitoring of ECG and metabolic changes is recommended before early repeated high doses are administered.