Nonlinear measures of QT interval series: novel indices of cardiac repolarization lability: MEDqthr and LLEqthr

In this study, we investigated nonlinear measures of chaos of QT interval time series in 28 normal control subjects, 36 patients with panic disorder and 18 patients with major depression in supine and standing postures. We obtained the minimum embedding dimension (MED) and the largest Lyapunov exponent (LLE) of instantaneous heart rate (HR) and QT interval series. MED quantifies the system's complexity and LLE predictability. There was a significantly lower MED and a significantly increased LLE of QT interval time series in patients. Most importantly, nonlinear indices of QT/HR time series, MEDqthr (MED of QT/HR) and LLEqthr (LLE of QT/HR), were highly significantly different between controls and both patient groups in either posture. Results remained the same even after adjusting for age. The increased LLE of QT interval time, series in patients with anxiety and depression is in line with our previous findings of higher QTvi (QT variability index, a log ratio of QT variability corrected for mean QT squared divided by heart rate variability corrected for mean heart rate squared) in these patients, using linear techniques. Increased LLEqthr (LLE of QT/HR) may be a more sensitive tool to study cardiac repolarization and a valuable addition to the time domain measures such as QTvi. This is especially important in light of the finding that LLEqthr correlated poorly and nonsignificantly with QTvi. These findings suggest an increase in relative cardiac sympathetic activity and a decrease in certain aspects of cardiac vagal function in patients with anxiety as well as depression. The lack of correlation between QTvi and LLEqthr suggests that this nonlinear index is a valuable addition to the linear measures. These findings may also help to explain the higher incidence of cardiovascular mortality in patients with anxiety and depressive disorders. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Organic pollution in culture water resulting from excess feed and metabolite buildup

Penaeus monodon postlarvae were subjected to increasing feed concentrations and their growth and survival rates were recorded. Measurements were made of dissolved organic matter, and ammonia and nitrite-nitrogen concentrations. Survival was highest at the lowest feeding level and decreased as feed concentration increased. It is concluded that although organic matter enriches the food supply for P. monodon postlarvae, at higher concentration levels it can pollute the culture water, which in turn leads to mass mortality of the postlarvae. Secondly, the survival rate of P. monodon postlarvae is directly related to dissolved organic matter concentration, oxygen tension, and ammonia-nitrogen concentrations in the culture water. Even at sublethal levels these adverse environmental conditions decrease the survival rate.

Nonlinear analysis of cardiac rhythm fluctuations using DFA method

An approach by which the detrented fluctuation analysis (DFA) method can be used to help diagnose heart failure was demonstrated. DFA was applied to patients suffering from congestive heart failure (CHF) to check correlations between DFA indices and CHF, and determine a correlation between DFA indices and mortality, with a particular attention to the residue parameter, which is a measure of the departure of the DFA from its power law approximation. DFA parameters proved to be useful as a complement to the physiological parameters weber and FE to sort out the patients into three prognostic group.

Prediction of 30-day mortality in older patients with a first acute myocardial infarction

This study sought predictors of mortality in patients aged >or=75 years with a first ST-segment elevation myocardial infarction (STEMI) and evaluated the validity of the GUSTO-I and TIMI risk models. Clinical variables, treatment and mortality data from 433 consecutive patients were collected. Univariable and multivariable logistic regression analyses were applied to identify baseline factors associated with 30-day mortality. Subsequently a model predicting 30-day mortality was created and compared with the performance of the GUSTO-I and TIMI models. After adjustment, a higher Killip class was the most important predictor (OR 16.1; 95% CI 5.7-45.6). Elevated heart rate, longer time delay to admission, hyperglycemia and older age were also associated with increased risk. Patients with hypercholesterolemia had a significantly lower risk (OR 0.46; 95% CI 0.24-0.86). Discrimination (c-statistic 0.79, 95% CI 0.75-0.84) and calibration (Hosmer-Lemeshow 6, p = 0.5) of our model were good. The GUSTO-I and TIMI risk scores produced adequate discrimination within our dataset (c-statistic 0.76, 95% CI 0.71-0.81, and c-statistic 0.77, 95% CI 0.72-0.82, respectively), but calibration was not satisfactory (HL 21.8, p = 0.005 for GUSTO-I, and HL 20.6, p = 0.008 for TIMI). In conclusion, short-term mortality in elderly patients with a first STEMI depends most importantly on initial clinical and hemodynamic status. The GUSTO-I and TIMI models are insufficiently adequate for providing an exact estimate of 30-day mortality risk.

Platelet Counts, Acute Kidney Injury, and Mortality after Coronary Artery Bypass Grafting Surgery.

BACKGROUND: Cardiac surgery requiring cardiopulmonary bypass is associated with platelet activation. Because platelets are increasingly recognized as important effectors of ischemia and end-organ inflammatory injury, the authors explored whether postoperative nadir platelet counts are associated with acute kidney injury (AKI) and mortality after coronary artery bypass grafting (CABG) surgery. METHODS: The authors evaluated 4,217 adult patients who underwent CABG surgery. Postoperative nadir platelet counts were defined as the lowest in-hospital values and were used as a continuous predictor of postoperative AKI and mortality. Nadir values in the lowest 10th percentile were also used as a categorical predictor. Multivariable logistic regression and Cox proportional hazard models examined the association between postoperative platelet counts, postoperative AKI, and mortality. RESULTS: The median postoperative nadir platelet count was 121 × 10/l. The incidence of postoperative AKI was 54%, including 9.5% (215 patients) and 3.4% (76 patients) who experienced stages II and III AKI, respectively. For every 30 × 10/l decrease in platelet counts, the risk for postoperative AKI increased by 14% (adjusted odds ratio, 1.14; 95% CI, 1.09 to 1.20; P < 0.0001). Patients with platelet counts in the lowest 10th percentile were three times more likely to progress to a higher severity of postoperative AKI (adjusted proportional odds ratio, 3.04; 95% CI, 2.26 to 4.07; P < 0.0001) and had associated increased risk for mortality immediately after surgery (adjusted hazard ratio, 5.46; 95% CI, 3.79 to 7.89; P < 0.0001). CONCLUSION: The authors found a significant association between postoperative nadir platelet counts and AKI and short-term mortality after CABG surgery.

Practice-Level Variation in Outpatient Cardiac Care and Association With Outcomes.

BACKGROUND: Utilization of cardiac services varies across regions and hospitals, yet little is known regarding variation in the intensity of outpatient cardiac care across cardiology physician practices or the association with clinical endpoints, an area of potential importance to promote efficient care. METHODS AND RESULTS: We included 7 160 732 Medicare beneficiaries who received services from 5635 cardiology practices in 2012. Beneficiaries were assigned to practices providing the plurality of office visits, and practices were ranked and assigned to quartiles using the ratio of observed to predicted annual payments per beneficiary for common cardiac services (outpatient intensity index). The median (interquartile range) outpatient intensity index was 1.00 (0.81-1.24). Mean payments for beneficiaries attributed to practices in the highest (Q4) and lowest (Q1) quartile of outpatient intensity were: all cardiac payments (Q4 $1272 vs Q1 $581; ratio, 2.2); cardiac catheterization (Q4 $215 vs Q1 $64; ratio, 3.4); myocardial perfusion imaging (Q4 $253 vs Q1 $83; ratio, 3.0); and electrophysiology device procedures (Q4 $353 vs Q1 $142; ratio, 2.5). The adjusted odds ratios (95% CI) for 1 incremental quartile of outpatient intensity for each outcome was: cardiac surgical/procedural hospitalization (1.09 [1.09, 1.10]); cardiac medical hospitalization (1.00 [0.99, 1.00]); noncardiac hospitalization (0.99 [0.99, 0.99]); and death at 1 year (1.00 [0.99, 1.00]). CONCLUSION: Substantial variation in the intensity of outpatient care exists at the cardiology practice level, and higher intensity is not associated with reduced mortality or hospitalizations. Outpatient cardiac care is a potentially important target for efforts to improve efficiency in the Medicare population.

CB1 cannabinoid receptor deficiency promotes cardiac remodeling induced by pressure overload in mice

Background: The endocannabinoid system is known to play a role in regulating myocardial contractility, but the influence of cannabinoid receptor 1 (CB1) deficiency on chronic heart failure (CHF) remains unclear. In this study we attempted to investigate the effect of CB1 deficiency on CHF induced by pressure overload and the possible mechanisms involved. Methods and results: A CHF model was created by transverse aortic constriction (TAC) in both CB1 knockout mice and wild-type mice. CB1 knockout mice showed a marked increase of mortality due to CHF from 4 to 8 weeks after TAC (p = 0.021). Five weeks after TAC, in contrast to wild-type mice, CB1 knockout mice had a higher left ventricular (LV) end-diastolic pressure, lower rate of LV pressure change (± dp/dt max), lower LV contractility index, and a larger heart weight to body weight ratio and lung weight to body weight ratio compared with wild-type mice (all p < 0.05-0.001). Phosphorylation of the epidermal growth factor receptor (EGFR) and mitogen-activated protein kinases (P38 and ERK) was higher in CB1 knockout mice than that in wild-type mice. In cultured neonatal rat cardiomyocytes, a CB1 agonist reduced cAMP production stimulated by isoproterenol or forskolin, and suppressed phosphorylation of the EGFR, P38, and ERK, while the inhibitory effect of a CB1 agonist on EGFR phosphorylation was abrogated by CB1 knockdown. Conclusion: These findings indicate that cannabinoid receptor 1 inactivation promotes cardiac remodeling by enhancing the activity of the epidermal growth factor receptor and mitogen-activated protein kinases. © 2012 Elsevier Ireland Ltd.

Demographic and temporal trends in out of hospital sudden cardiac death in belfast

Objective: To determine the epidemiology of out of hospital sudden cardiac death (OHSCD) in Belfast from 1 August 2003 to 31 July 2004.

Design: Prospective examination of out of hospital cardiac arrests by using the Utstein style and necropsy reports. World Health Organization criteria were applied to determine the number of sudden cardiac deaths.

Results: Of 300 OHSCDs, 197 (66%) in men, mean age (SD) 68 (14) years, 234 (78%) occurred at home. The emergency medical services (EMS) attended 279 (93%). Rhythm on EMS arrival was ventricular fibrillation (VF) in 75 (27%). The call to response interval (CRI) was mean (SD) 8 (3) minutes. Among patients attended by the EMS, 9.7% were resuscitated and 7.2% survived to leave hospital alive. The CRI for survivors was mean (SD) 5 (2) minutes and for non-survivors, 8 (3) minutes (p < 0.001). Ninety one (30%) OHSCDs were witnessed; of these 91 patients 48 (53%) had VF on EMS arrival. The survival rate for witnessed VF arrests was 20 of 48 (41.7%): all 20 survivors had VF as the presenting rhythm and CRI ? 7 minutes. The European age standardised incidence for OHSCD was 122/100 000 (95% confidence interval 111 to 133) for men and 41/100 000 (95% confidence interval 36 to 46) for women.

Conclusion: Despite a 37% reduction in heart attack mortality in Ireland over the past 20 years, the incidence of OHSCD in Belfast has not fallen. In this study, 78% of OHSCDs occurred at home.

Burnout as a predictor of all-cause mortality among industrial employees: A 10-year prospective register-linkage study

Objective: Burnout, a psychological consequence of prolonged work stress, has been shown to coexist with physical and mental disorders. The aim of this study was to investigate whether burnout is related to all-cause mortality among employees. Methods: In 1996, of 15,466 Finnish forest industry employees, 9705 participated in the 'Still Working' study and 8371 were subsequently identified from the National Population Register. Those who had been treated in a hospital for the most common causes of death prior to the assessment of burnout were excluded on the basis of the Hospital Discharge Register, resulting in a final study population of 7396 people. Burnout was measured using the Maslach Burnout Inventory-General Survey. Dates of death from 1996 to 2006 were extracted from the National Mortality Register. Mortality was predicted with Cox hazard regression models, controlling for baseline sociodemographic factors and register-based health status according to entitled medical reimbursement and prescribed medication for mental health problems, cardiac risk factors, and pain problems. Results: During the 10-year 10-month follow-up, a total of 199 employees had died. The risk of mortality per one-unit increase in burnout was 35% higher (95% CI 1.07-1.71) for total score and 26% higher (0.99-1.60) for exhaustion, 29% higher for cynicism (1.03-1.62), and 22% higher for diminished professional efficacy (0.96-1.55) in participants who had been under 45 at baseline. After adjustments, only the associations regarding burnout and exhaustion were statistically significant. Burnout was not related to mortality among the older employees. Conclusion: Burnout, especially work-related exhaustion, may be a risk for overall survival. (C) 2010 Elsevier Inc. All rights reserved.

Modelling coronary heart disease mortality in Northern Ireland between 1987 and 2007: broader lessons for prevention

To quantify how much of the coronary heart disease (CHD) mortality decline in Northern Ireland between 1987 and 2007 could be attributed to medical and surgical treatments and how much to changes in population cardiovascular risk factors.

Cause-specific mortality adjudication in the UPLIFT® COPD trial:findings and recommendations

Mortality is an important endpoint in chronic obstructive pulmonary disease (COPD) trials, although accurately determining cause of death is difficult. In the Understanding the Potential Long-term Impacts on Function with Tiotropium (UPLIFT®) trial, a mortality adjudication committee (MAC) provided systematic, independent and blinded assessment of cause-specific mortality of all 981 reported deaths. Here we describe this process of mortality adjudication and methodological revisions introduced to help standardise the adjudication of two areas recognised to pose particular difficulty; firstly, the classification of fatal COPD exacerbations that occur in the setting of pneumonia and secondly, the categorisation of sudden death. In addition MAC determined cause of death was compared with that reported by site investigators (SIs). MAC-assigned causes of death were: respiratory, 35%; cancer, 25%; cardiovascular, 11%; sudden cardiac death, 4.4%; sudden death, 3.4%; other, 8.8%; unknown, 12.4%. Cancer/cardiac deaths were more common in Global Initiative for Chronic Obstructive Lung Disease stage II, respiratory deaths in stages III and IV. Agreement between MAC and SI regarding cause of death was complete (50.2%), incomplete (18.5%) or none (31.3%). The SI classified deaths as cardiac three-fold more frequently than MAC (incidence rate [IR]/100 patient-years 0.797 vs. 0.257), although IR ratios for cardiac deaths for tiotropium vs. control were similar between SI and MAC. Discrepancies between MAC- and SI-adjudicated causes of death are common, especially increased reporting of cardiac deaths by the SI. Future multicentre COPD trials should plan appropriate infrastructure before study initiation to ensure collection and interpretation of fatal events data.

Comparing the decline in coronary heart disease and stroke mortality in neighbouring countries with different healthcare systems

Objective
To examine age and gender specific trends in coronary heart disease (CHD) and stroke mortality in two neighbouring countries, the Republic of Ireland (ROI) and Northern Ireland (NI). Design Epidemiological study of time trends in CHD and stroke mortality.

Setting/patients
The populations of the ROI and NI, 1985–2010.

Interventions
None.

Main outcome measures
Directly age standardised CHD and stroke mortality rates were calculated and analysed using joinpoint regression to identify years where the slope of the linear trend changed significantly. This was performed separately for specific age groups (25–54, 55–64, 65–74 and 75–84 years) and by gender. Annual percentage change (APC) and 95% CIs are presented.

Results
There was a striking similarity between the two countries, with percentage change between 1985 and 1989 and between 2006 and 2010 of 67% and 69% in
CHD mortality, and 64% and 62% in stroke mortality for the ROI and NI, respectively. However, joinpoint analysis identified differences in the pace of change between the two countries. There was an accelerated pace of decline (negative APC) in mortality for both CHD and stroke in both countries from the mid-1990s (APC ROI −8% (95% CI −9.5 to 6.5) and NI −6.6% (−6.9 to −6.3)), but the accelerated decrease started later for CHD mortality in the ROI. In recent years, a levelling off in CHD mortality was observed in the 25–54 year age group in NI and in stroke mortality for men and women in the ROI.

Conclusions
While differences in the pace of change in mortality were observed at different time points, similar, substantial decreases in CHD and stroke mortality were achieved between 1985 and 1989 and between 2006 and 2010 in the ROI and NI despite important differences in health service structures. There is evidence of a levelling in mortality rates in some groups in recent years.

Streptococcus bovis bacteraemia: an evaluation of the long-term effect on cardiac outcomes

Introduction: Streptococcus bovis can lead to bacteraemia, septicaemia, and ultimately endocarditis. The objective of this study was to evaluate the long-term implications of S. bovis endocarditis on cardiac morbidity and mortality. 

Methods: A retrospective cohort study was performed between January 2000 and March 2009 to assess all patients diagnosed with S. bovis bacteraemia from the Belfast Health and Social Care Trust. The primary end-point for cardiac investigations was the presence of endocarditis. Secondary end-points included referral for cardiac surgery and overall mortality. 

Results: Sixty-one positive S. bovis blood cultures from 43 patients were included. Following echocardiography, seven patients were diagnosed with infective endocarditis (16.3 % of total patients); four patients (9.3 %) had native valve involvement while three (7.0 %) had prosthetic valve infection. Five of these seven patients had more than one positive S. bovis culture (71.4 %). Three had significant valve dysfunction that warranted surgical repair/replacement, one of whom was unfit for surgery. There was a 100 % recurrence rate amongst the valve replacement patients (n = 2) and six patients with endocarditis had colorectal pathology. Patients with endocarditis had similar long-term survival as those with non-endocarditic bacteraemia (57.1 % alive vs. 50 % of non-endocarditis patients, p = 0.73). 

Conclusion: Streptococcus bovis endocarditis patients tended to have pre-existing valvular heart disease and those with prosthetic heart valves had higher surgical intervention and relapse rates. These patients experienced a higher rate of co-existing colorectal pathology but currently have reasonable long-term outcomes. This may suggest that they represent a patient population that merits consideration for an early surgical strategy to maximise long-term results, however, further evaluation is warranted. © 2013 The Japanese Association for Thoracic Surgery.

Impact of smoking and smoking cessation on cardiovascular events and mortality among older adults: meta-analysis of individual participant data from prospective cohort studies of the CHANCES consortium

OBJECTIVE: To investigate the impact of smoking and smoking cessation on cardiovascular mortality, acute coronary events, and stroke events in people aged 60 and older, and to calculate and report risk advancement periods for cardiovascular mortality in addition to traditional epidemiological relative risk measures.

DESIGN: Individual participant meta-analysis using data from 25 cohorts participating in the CHANCES consortium. Data were harmonised, analysed separately employing Cox proportional hazard regression models, and combined by meta-analysis.

RESULTS: Overall, 503,905 participants aged 60 and older were included in this study, of whom 37,952 died from cardiovascular disease. Random effects meta-analysis of the association of smoking status with cardiovascular mortality yielded a summary hazard ratio of 2.07 (95% CI 1.82 to 2.36) for current smokers and 1.37 (1.25 to 1.49) for former smokers compared with never smokers. Corresponding summary estimates for risk advancement periods were 5.50 years (4.25 to 6.75) for current smokers and 2.16 years (1.38 to 2.39) for former smokers. The excess risk in smokers increased with cigarette consumption in a dose-response manner, and decreased continuously with time since smoking cessation in former smokers. Relative risk estimates for acute coronary events and for stroke events were somewhat lower than for cardiovascular mortality, but patterns were similar.

CONCLUSIONS: Our study corroborates and expands evidence from previous studies in showing that smoking is a strong independent risk factor of cardiovascular events and mortality even at older age, advancing cardiovascular mortality by more than five years, and demonstrating that smoking cessation in these age groups is still beneficial in reducing the excess risk.

Which biomarkers are predictive specifically for cardiovascular or for non-cardiovascular mortality in men? Evidence from the Caerphilly Prospective Study (CaPS)

OBJECTIVE: To examine a panel of 28 biomarkers for prediction of cardiovascular disease (CVD) and non-CVD mortality in a population-based cohort of men.

METHODS: Starting in 1979, middle-aged men in Caerphilly underwent detailed medical examination. Subsequently 2171 men were re-examined during 1989-1993, and fasting blood samples obtained from 1911 men (88%). Fibrinogen, viscosity and white cell count (WCC), routine biochemistry tests and lipids were analysed using fresh samples. Stored aliquots were later analysed for novel biomarkers. Statistical analysis of CVD and non-CVD mortality follow-up used competing risk Cox regression models with biomarkers in thirds tested at the 1% significance level after covariate adjustment.

RESULTS: During an average of 15.4years follow-up, troponin (subhazard ratio per third 1.71, 95% CI 1.46-1.99) and B-natriuretic peptide (BNP) (subhazard ratio per third 1.54, 95% CI 1.34-1.78) showed strong trends with CVD death but not with non-CVD death. WCC and fibrinogen showed similar weaker findings. Plasma viscosity, growth differentiation factor 15 (GDF-15) and interleukin-6 (IL-6) were associated positively with both CVD death and non-CVD death while total cholesterol was associated positively with CVD death but negatively with non-CVD death. C-reactive protein (C-RP), alkaline phosphatase, gamma-glutamyltransferase (GGT), retinol binding protein 4 (RBP-4) and vitamin B6 were significantly associated only with non-CVD death, the last two negatively. Troponin, BNP and IL-6 showed evidence of diminishing associations with CVD mortality through follow-up.

CONCLUSION: Biomarkers for cardiac necrosis were strong, specific predictors of CVD mortality while many inflammatory markers were equally predictive of non-CVD mortality.