Adrenomedullin and endothelin-1 are hormones with opposing effects on the cardiovascular system. Adrenomedullin acts as a vasodilator and seems to be important for the initiation and continuation of the hyperdynamic circulatory response in sepsis. Endothelin-1 is a vasoconstrictor and has been linked to decreased cardiac performance. Few studies have studied the relationship between adrenomedullin and endothelin-1, and morbidity and mortality in septic shock patients. High-sensitivity troponin T (hsTNT) is normally used to diagnose acute cardiac injury but is also prognostic for outcome in intensive care. We investigated the relationship between mid-regional pro-adrenomedullin (MR-proADM), C-terminal pro-endothelin-1 (CT-proET-1), and myocardial injury, measured using transthoracic echocardiography and hsTNT in septic shock patients. We were also interested in the development of different biomarkers throughout the ICU stay, and how early measurements were related to mortality. Further, we assessed if a positive biomarker panel, consisting of MR-proADM, CT-proET-1, and hsTNT changed the odds for mortality.
A cohort of 53 consecutive patients with septic shock had their levels of MR-proADM, CT-proET-1, hsTNT, and left ventricular systolic functions prospectively measured over 7 days. The relationship between day 1 levels of MR-proADM/CT-proET-1 and myocardial injury was studied. We also investigated the relationship between biomarkers and early (7-day) and later (28-day) mortality. Likelihood ratios, and pretest and posttest odds for mortality were calculated.
Levels of MR-proADM and CT-proET-1 were significantly higher among patients with myocardial injury and were correlated with left ventricular systolic dysfunction. MR-proADM and hsTNT were significantly higher among 7-day and 28-day non-survivors. CT-proET-1 was also significantly higher among 28-day but not 7-day non-survivors. A positive biomarker panel consisting of the three biomarkers increased the odds for mortality 13-fold to 20-fold.
MR-proADM and CT-proET-1 are associated with myocardial injury. A biomarker panel combining MR-proADM, CT-proET-1, and hsTNT increases the odds ratio for death, and may improve currently available scoring systems in critical care.
In cardiac transplantation, the donor organ is not initially innervated and demonstrates decreased heart rate variability (HRV). However, HRV may improve after several months. The mechanism for HRV improvement has not been elucidated; autonomic "reinnervation" of the donor heart has been proposed. The role of atrioatrial conduction from recipient to donor organ has not been evaluated. We prospectively evaluated cardiac transplant patients with a limited electrophysiology study at the time of their surveillance biopsies. Recordings were made of recipient and donor signals, observing conduction properties between recipient and donor atria. Holter recordings were analyzed and HRV was determined using spectral analysis techniques, recording mean RR interval, low-frequency power (LF), high-frequency power (HF), and the LF/HF ratio. These were compared to published norms. From November 1999 to May 2000, 21 patients (6 female) who underwent cardiac transplantation participated at a median age of 101 months (range, 4.1-217 months). Time posttransplant ranged from 26 days to 71 months. Holter data were available for 20 patients and demonstrated dissociated P waves in 13 (65%). The mean heart rate on Holter was 111 beats per minute (bpm) (range, 85-161 bpm). We were able to record distinct recipient atrial signals in 16 of 21 (76%) patients. The average recipient tissue heart rate was 55% that of the donor heart rate. We documented atrioatrial association in only 1 patient. HRV did not reach normal values for most patients and did not increase with time posttransplantation. The LF values were in the normal range for most patients, whereas 3 patients had normal HF values and 2 patients had values just below normal. Recipients of heart transplantation have a predominantly sympathetic influence of HRV. These preliminary data suggest that atrioatrial conduction does not play a role in reestablishing normal heart rate control following pediatric cardiac transplantation.
The safety of metformin in heart failure has been questioned because of a perceived risk of life-threatening lactic acidosis, though recent studies have not supported this concern. We investigated the risk of all-cause mortality associated with individual glucose-lowering treatment regimens used in current clinical practice in Denmark.
All patients aged = 30 years hospitalised for the first time for heart failure in 1997-2006 were identified and followed until the end of 2006. Patients who received treatment with metformin, a sulfonylurea and/or insulin were included and assigned to mono-, bi- or triple therapy groups. Multivariable Cox proportional hazard regression models were used to assess the risk of all-cause mortality.
A total of 10,920 patients were included. The median observational time was 844 days (interquartile range 365-1,395 days). In total, 6,187 (57%) patients died. With sulfonylurea monotherapy used as the reference, adjusted hazard ratios for all-cause mortality associated with the different treatment groups were as follows: metformin 0.85 (95% CI 0.75-0.98, p = 0.02), metformin + sulfonylurea 0.89 (95% CI 0.82-0.96, p = 0.003), metformin + insulin 0.96 (95% CI 0.82-1.13, p = 0.6), metformin + insulin + sulfonylurea 0.94 (95% CI 0.77-1.15, p = 0.5), sulfonylurea + insulin 0.97 (95% CI 0.86-1.08, p = 0.5) and insulin 1.14 (95% CI 1.06-1.20, p = 0.0001).
Treatment with metformin is associated with a low risk of mortality in diabetic patients with heart failure compared with treatment with a sulfonylurea or insulin.
Dilated (DCM), restrictive (RCM), and hypertrophic (HCM) cardiomyopathies (CM) in children have varying clinical courses and therapeutic options. Heart transplantation (HTx) offers a chance for long-term survival; but outcomes after listing have not been well defined.
A multi-institutional registry of 3,147 patients listed for HTx (January 1993-December 2006) was used to compare outcomes of 1,320 children with CM (42%) and 1,827 with non-CM (58%) etiologies. Comparisons were made between sub-groups: 1,098 DCM (83%), 145 RCM (11%), and 77 HCM (6%).
CM patients had a waitlist mortality of 17% vs 32% for non-CM patients (p
To predict mortality risk and life expectancy for patients with type 2 diabetes after a major diabetes-related complication.
The study sample, taken from the Swedish National Diabetes Register, consisted of 20 836 people with type 2 diabetes who had their first major complication (myocardial infarction, stroke, heart failure, amputation or renal failure) between January 2001 and December 2007. A Gompertz proportional hazards model was derived which determined significant risk factors associated with mortality and was used to estimate life expectancies.
Risk of death changed over time according to type of complication, with myocardial infarction initally having the highest initial risk of death, but after the first month, the risk was higher for heart failure, renal failure and amputation. Other factors that increased the risk of death were male gender (hazard ratio 1.06, 95% CI 1.02-1.12), longer duration of diabetes (hazard ratio 1.07 per 10 years, 95% CI 1.04-1.10), smoking (hazard ratio 1.51, 95% CI 1.40-1.63) and macroalbuminuria (hazard ratio 1.14, 95% CI 1.06-1.22). Low BMI, low systolic blood pressure and low estimated GFR also increased mortality risk. Life expectancy was highest after a stroke, myocardial infarction or heart failure, lower after amputation and lowest after renal failure. Smoking and poor renal function were the risk factors which had the largest impact on reducing life expectancy.
Risk of death and life expectancy differs substantially among the major complications of diabetes, and factors significantly increasing risk included smoking, low estimated GFR and albuminuria.
Aim of this study was determination of incidence and structure of sudden out of hospital cardiac death (SCD) in subjects aged 1-45 years in Moscow. We analyzed rate and structure of SD among persons who had succumbed in 2005-2007 in several districts of Moscow with population of 2,502,836. Of the total number of 19,557 autopsies 7702 (39.4% or 92/100 000/year) and 1265 (6.5%, 19.4% of autopsies in this age group, or 16.8/100000/year) in all age groups and in the age 1-45 years, respectively, were performed because of SCD. In most cases (44%) age at SCD was 41-45 years, only in 1% of cases it was less than 18 years. Eighty two percent of autopsied SD victims were men. Most frequent postmortem diagnosis was "cardiomyopathy" (69% overall, 80-96% in the age 19-35 years) established on the basis of detection of both specific and nonspecific changes in the myocardium. In 25% of SD cases in the age group before 18 years congenital heart disease was found. After 35 years rose portion of diseases of ischemic nature (22-32%). Percentages of hypertensive disease and other diseases among all diagnoses were 7 and 1, respectively. Beginning with 19 years in large percentage of cases presence of alcohol in blood was detected. This percentage was especially high in the age group 19-25 years (66.6%). SCD of most persons aged 20-45 years was registered at home, while in 50% of younger persons it occurred outside home often during physical effort. Rate of SCD, its circumstances and structure elicited in this study might serve as basis for elaboration of the system of early detection of groups of risk and prevention of SD in young age.
Heart transplantation (HTx) has become a standard treatment for patients with end-stage heart disease. The aim of this study was to report the long-term outcome after HTx in Scandinavia.
During the period, 1983-2009, 2333 HTxs were performed in 2293 patients (mean age 45 ± 16 years, range 0-70, 78% male). The main indications for HTx were non-ischaemic cardiomyopathy (50%), ischaemic cardiomyopathy (34%), valvular cardiomyopathy (3%), congenital heart disease (7%), retransplantation (2%), and miscellaneous (4%). The registry consists of pre-operative data from recipients and donors, data from pre-operative procedures, and long-term follow-up data. Mean follow-up was 7.8 ± 6.6 years (median 6.9, interquartile range 2.5-12.3, interval 0-27) and no patients were lost to follow-up. Long-term survival for HTx patients was 85, 76, 61, 43, and 30% at 1, 5, 10, 15, and 20 years of follow-up, respectively. Ten-year survival in patients bridged with mechanical circulatory support, in children, after retransplantation, and after concomitant other organ transplantation was 56, 74, 38, and 43%, respectively. Older patients (age > 55 years) had a significantly worse survival (P
Data on the prognostic impact of diabetes and diabetic complications in intensive care unit (ICU) patients are limited and inconsistent. We, therefore, examined mortality in ICU patients with type 2 diabetes with and without pre-existing heart and kidney diseases compared with nondiabetic patients.
We conducted this population-based cohort study in Northern Denmark during 2005-2011. We included all ICU patients aged 40 years or older from the 17 ICUs in the area and identified type 2 diabetes by either a filled prescription for an antidiabetic drug, a previous diagnosis of diabetes, or an elevated glycosylated haemoglobin level. Diabetic patients were disaggregated according to pre-existing diagnoses of heart disease (myocardial infarction or heart failure) and kidney disease. We estimated 1-year mortality by the Kaplan-Meier method and hazard ratios of death (HRs) during follow-up using Cox regression, controlling for confounding factors and stratified by relevant subgroups.
Among 45 018 ICU patients, 7219 (16·0%) had type 2 diabetes. Overall, 1-year mortality was 36·0% in ICU patients with type 2 diabetes, rising to 54·6% in patients with pre-existing heart and kidney diseases, compared with 29·1% in nondiabetic patients. Comparing diabetic with nondiabetic patients, the adjusted 0- to 30-day HR was 1·20 (95% confidence interval (CI): 1·13-1·26) and 1·19 (95% CI: 1·10-1·28) during the 31- to 365-day follow-up period. Pre-existing kidney disease further increased the impact of diabetes, while heart disease alone had no such effect.
ICU patients with type 2 diabetes had higher 1-year mortality compared with nondiabetic ICU patients, particularly those with pre-existing kidney disease.