Association of Central Venous Oxygen Saturation Variability and Mortality in Hemodialysis Patients.

BACKGROUND: Central venous oxygen saturation (ScvO2) is correlated with cardiac output. In most patients, ScvO2 declines during hemodialysis (HD) due to factors such as reduced preload, myocardial stunning, and intermittent arrhythmias. Previous research has shown that low ScvO2 is associated with higher mortality in chronic HD patients. In this research, we tested the hypothesis that ScvO2 variability is associated with all-cause mortality. METHODS: We conducted a retrospective study in 232 chronic HD patients with central venous catheter as vascular access. ScvO2 was recorded 1× per minute during dialysis using the Crit-Line monitor. A 6-month baseline comprising at least 10 dialysis treatments with ScvO2 recordings preceded a follow-up period of up to 3 years. The coefficient of variation (CV) of ScvO2 (100 times the ratio of the standard deviation and mean of ScvO2) served as a measure of ScvO2 stability during baseline. Patients were stratified by median population CV of ScvO2 during baseline, and survival during follow-up was compared between the 2 groups by Kaplan Meier and multivariate Cox analysis. The association between CV of ScvO2 and all-cause mortality during follow-up was further assessed by Cox analysis with a spline term for CV of ScvO2. RESULTS: The mean CV ± standard deviation of ScvO2 in our population was 6.1 ± 2.7% and the median was 5.3%. Univariate Kaplan-Meier analysis (p = 0.043) and multivariate Cox analysis (hazard ratio [HR] 1.16; p = 0.0005) indicated that a CV of ScvO2 > 5.3% was significantly associated with increased mortality. In Cox analysis with spline term, a CV of ScvO2 >  11% was associated with a significantly increased HR for all-cause mortality. CONCLUSION: High ScvO2 variability during dialysis is associated with increased all-cause mortality.

Impact of basal inferolateral scar burden determined by automatic analysis of 99mTc-MIBI myocardial perfusion SPECT on the long-term prognosis of cardiac resynchronization therapy.

AIMS: Left-ventricular (LV) scarring may be associated with a poor response to cardiac resynchronization therapy (CRT). The automatic analysis of myocardial perfusion single-photon emission computed tomography (MP-SPECT) may provide objective quantification of LV scarring. We investigated the impact of LV scarring determined by an automatic analysis of MP-SPECT on short-term LV volume response as well as long-term outcome. METHODS AND RESULTS: We studied consecutive 51 patients who were eligible to undergo 99mTc-MIBI MP-SPECT both at baseline and 6 months after CRT (ischaemic cardiomyopathies 31%). Quantitative perfusion SPECT was used to evaluate the defect extent (an index of global scarring) and the LV 17-segment regional uptake ratio (an inverse index of regional scar burden). The primary outcome was the composite of overall mortality or first hospitalization for worsening heart failure. A high global scar burden and a low mid/basal inferolateral regional uptake ratio were associated with volume non-responders to CRT at 6 months. The basal inferolateral regional uptake ratio remained as a predictor of volume non-response after adjusting for the type of cardiomyopathy. During a median follow-up of 36.1 months, the outcome occurred in 28 patients. The patients with a low basal inferolateral regional uptake ratio with a cutoff value of 57% showed poor prognosis (log-rank P= 0.006). CONCLUSION: The scarring determined by automatic analysis of MP-SPECT images may predict a poor response to CRT regardless of the pathogenesis of cardiomyopathy. The basal inferolateral scar burden in particular may have an adverse impact on long-term prognosis.

Citric Acid Cycle Metabolites Predict the Severity of Myocardial Stunning and Mortality in Newborn Pigs.

OBJECTIVES: Myocardial infarction and chronic heart failure induce specific metabolic changes in the neonatal myocardium that are closely correlated to outcome. The aim of this study was to examine the metabolic responses to noninfarct heart failure and inotropic treatments in the newborn heart, which so far are undetermined. DESIGN: A total of 28 newborn pigs were instrumented with a microdialysis catheter in the right ventricle, and intercellular citric acid cycle intermediates and adenosine metabolite concentrations were determined at 20-minute intervals. Stunning was induced by 10 cycles of 3 minutes of ischemia, which was performed by occluding the right coronary artery, followed by 3 minutes of reperfusion. Animals were randomized for treatment with epinephrine + milrinone, dopamine + milrinone, dobutamine, or saline. SETTING: University hospital animal laboratory. MAIN RESULTS: Ischemia-reperfusion induced right ventricular stunning and increased the concentrations of pyruvate lactate, succinate, malate, hypoxanthine, and xanthine (all, p < 0.01). During inotrope infusion, no differences in metabolite concentrations were detected between the treatment groups. In nonsurviving animals (n = 8), concentrations of succinate (p < 0.0001), malate (p = 0.009), and hypoxanthine (p = 0.04) increased compared with survivors, while contractility was significantly reduced (p = 0.03). CONCLUSIONS: Accumulation of citric acid cycle intermediates and adenosine metabolites reflects the presence of myocardial stunning and predicts mortality in acute noninfarct right ventricular heart failure in newborn pigs. This phenomenon occurs independently of the type of inotrope, suggesting that citric acid cycle intermediates represent potential markers of acute noninfarct heart failure.

ECG myocardial scar quantification predicts reverse left ventricular remodeling and survival after cardiac resynchronization therapy implantation: A retrospective pilot study.

INTRODUCTION: Electrocardiographic (ECG) LV scar quantification may improve prediction of CRT response. METHODS AND RESULTS: Data were abstracted in 76 patients who underwent a first CRT implantation at 2 US centers. Selvester QRS scar quantification was performed using the LBBB modified QRS scoring method. Seven clinical variables previously associated with reverse LV remodeling (RLVR) and QRS score were included in logistic regression analysis. Survival was compared across QRS score quartiles using Kaplan-Meier curves. RLVR occurred more frequently in patients with QRS score ≤ 5 (63%) than QRS score>5 (22%), (OR=5.83, 95% CI=2.11-16.07). After adjustment for clinical variables using logistic regression, QRS score>5 predicted RLVR (Chi-square=20.3, P=0.005, AUC=0.782). Patients in the lowest quartile of QRS score (<4) had improved survival compared to patients in the other QRS score quartiles (P=0.037). CONCLUSION: ECG quantified LV scar predicts RLVR and long-term survival in patients with LBBB undergoing CRT implantation.

Impact of denervated myocardium on improving risk stratification for sudden cardiac death.

Between 184,000 and 462,000 Americans die suddenly each year. Fifty percent to 70% of these deaths are due to ventricular tachycardia/fibrillation (VT/VF). We tested whether hibernating myocardium or myocardial sympathetic denervation identifies patients at high-risk for developing VT/VF independently of ejection fraction (EF). Positron emission tomography (PET) was used to quantify myocardial sympathetic denervation ((11)C-meta-hydroxyephedrine [(11)C-HED]), perfusion ((13)N-ammonia), and viability (insulin-stimulated (18)F-2-deoxyglucose [(18)FDG]) in patients with ischemic cardiomyopathy (EF < 35%) eligible for a primary prevention implantable cardioverter defibrillator (ICD). The primary end-point was sudden cardiac arrest (SCA) defined as arrhythmic death or ICD discharge for VT/VF > 240 bpm. Volumes of total denervated (P = .001) and viable denervated myocardium ((11)C-HED-(18)FDG mismatch, P = .03) predicted SCA, whereas hibernating and infarcted myocardium did not. Multivariate analysis identified four independent predictors of SCA: denervated myocardium > 37.6% of left ventricule (LV), LV end-diastolic volume > 98 mL/m(2), creatinine level > 1.49 mg/dL, and no angiotensin- inhibition therapy. Denervated myocardium had a hazard ratio of 3.5 for SCA (10.3%/year vs. 3.0%/year, p=0.001). Absence of all four factors predicted low risk (44% of cohort; SCA <1%/y) whereas two or more factors identified subjects at high-risk (20% of cohort; SCA 12%/y). Denervated myocardium quantified using PET strongly predicts risk of SCA, and is independent of EF, infarct volume, and other clinical variables.

Identification of therapeutic benefit from revascularization in patients with left ventricular systolic dysfunction: inducible ischemia versus hibernating myocardium.

BACKGROUND: Although the recent surgical treatment of ischemic heart failure substudy reported that revascularization of viable myocardium did not improve survival, these results were limited by the viability imaging technique used and the lack of inducible ischemia information. We examined the relative impact of stress-rest rubidium-82/F-18 fluorodeoxyglucose positron emission tomography identified ischemia, scar, and hibernating myocardium on the survival benefit associated with revascularization in patients with systolic dysfunction. METHODS AND RESULTS: The extent of perfusion defects and metabolism-perfusion mismatch was measured with an automated quantitative method in 648 consecutive patients (age, 65±12 years; 23% women; mean left ventricular ejection fraction, 31±12%) undergoing positron emission tomography. Follow-up time began at 92 days (to avoid waiting-time bias); deaths before 92 days were excluded from the analysis. During a mean follow-up of 2.8±1.2 years, 165 deaths (27.5%) occurred. Cox proportional hazards modeling was used to adjust for potential confounders, including a propensity score to adjust for nonrandomized treatment allocation. Early revascularization was performed within 92 days of positron emission tomography in 199 patients (33%). Hibernating myocardium, ischemic myocardium, and scarred myocardium were associated with all-cause death (P=0.0015, 0.0038, and 0.0010, respectively). An interaction between treatment and hibernating myocardium was present such that early revascularization in the setting of significant hibernating myocardium was associated with improved survival compared with medical therapy, especially when the extent of viability exceeded 10% of the myocardium. CONCLUSIONS: Among patients with ischemic cardiomyopathy, hibernating, but not ischemic, myocardium identifies which patients may accrue a survival benefit with revascularization versus medical therapy.

Clinical characteristics and outcomes of neurogenic stress cadiomyopathy in aneurysmal subarachnoid hemorrhage.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is an often devastating form of stroke. Aside from the initial hemorrhage, cardiac complications can occur resulting in neurogenic stress cardiomyopathy (NCM), leading to impaired cardiac function. We investigated whether aSAH patients with NCM had poorer long term functional outcomes than patients without NCM. Mortality, vasospasm, and delayed ischemic complications were also evaluated. METHODS: A retrospective study of all patients admitted for aneurysmal subarachnoid hemorrhage (aSAH) from January 2006 to June 2011 (n=299) was conducted. Those patients who underwent an echocardiogram were identified (n=120) and were assigned to the NCM (n=49) category based on echocardiographic findings defined by a depressed ejection fraction (EF%) along with a regional wall motion abnormality (RWMA) in a non-vascular pattern. Primary outcome measures included in-hospital mortality and functional outcomes as measured by the Modified Barthel Index (mBI) at 3 months and one year. Secondary analysis determined if there was an association between NCM, cerebral vasospasm and delayed cerebral ischemia. RESULTS: 16% of aSAH patients developed NCM. Mortality was higher (p<.001) in the NCM group (n=23[46.9%]) than in the non-CM group (n=28[11.2%]). Patients with NCM had poorer functional outcomes as measured by the mBI at both 3 months (p=.002) and 12 months (p=.014). The Hunt-Hess score was predictive of functional outcome as measured by the mBI at both 3 months (p=.002) as well as at 1 year (p=.014). NCM was associated with both death (p=.047 CI, 1.012-7.288) and vasospasm (p=.008 CI, 1.34-6.66) after correction for Hunt-Hess grade. Tobacco use (p<.001) and a history of diabetes mellitus (p<.009) were also associated with vasospasm. NCM was associated with higher in-hospital mortality (p=.047) in multivariate analysis. CONCLUSION: NCM is seen in a substantial number of aSAH patients and when present, it is associated with higher mortality and poorer long-term functional outcomes. This finding may guide further prospective studies in order to determine if early recognition of NCM as well as optimization of cardiac output would improve mortality.

Preadmission beta-blockers are associated with decreased incidence of neurogenic stunned myocardium in aneurysmal subarachnoid hemorrhage.

BACKGROUND: Neurogenic stunned myocardium (NSM) is a frequent complication of aneurysmal subarachnoid hemorrhage (aSAH), with a significant impact on disease course. The presumed cause is catecholamine surge at the time of aneurysm rupture. Beta-blockers, which reduce the impact of the catecholamine surge, may decrease the risk of developing NSM. METHODS: A chart review of 234 consecutive patients admitted to the Oregon Health and Science University Neurosurgery service between March 6, 2008 and June 23, 2010 with a diagnosis of aneurysmal SAH was performed. This group was further subdivided by patients who received echocardiograms on admission, by gender, and by the prehospital administration of ß-blockers. RESULTS: One hundred thirty of 234 patients had echocardiograms on or shortly after admission, and 18 of these developed NSM (13.8%). None of the 22 patients taking prehospital ß-blockers developed NSM. Using the Fisher exact test to compare the 2 groups, patients who were administered prehospital ß-blockers were significantly less likely to develop stunning compared to those who were not (P = .04). After correcting for other variables using multiple logistic regression analysis, the previous use of ß-blockers was still found to be significantly associated with a decreased incidence of NSM after SAH (P = .049). There was no significant difference in hospital length of stay, peribleed stroke, vasospasm, or death. Of the 18 patients with stunning, 15 were women, 5 of whom were on estrogen supplementation. The mean peak troponin elevation of women who developed NSM on estrogen supplementation was significantly higher than for those who were not (mean peak troponin 9.97 ± 2.01 mg/dL; P < .001). CONCLUSION: Prehospital ß-blockers are associated with decreased risk of developing NSM in patients with aSAH. Estrogen may play an additional role in shaping the degree of NSM in women.

Troponin T levels in patients with acute heart failure: clinical and prognostic significance of their detection and release during hospitalisation.

AIMS: Myocardial injury during an episode of acute heart failure (AHF) may be important for patents' outcome. We hypothesised that an increase of cardiac troponin levels (cTnT) during hospitalisation, in patients with undetectable levels on admission (cTnT release), may be a more specific marker of myocardial damage. With this aim, we assessed the clinical and prognostic significance of high serum cTnT levels at the time of admission and that of cTnT release in 198 consecutive patients admitted for AHF and with no signs of acute coronary syndrome. METHODS AND RESULTS: cTnT levels were serially measured at the time of admission, and after 6 and 12 h, in 198 consecutive patients admitted for AHF and with no signs of acute coronary syndrome. cTnT was detectable (>0.01 ng/mL) in 102 patients (52 %) and positive for myocardial necrosis (>0.03 ng/mL) in 78 patients (39 %). Negative cTnT at the time of admission became positive at 6 and/or 12 h in 36 (18 %) patients. Patients with increased cTnT levels were more likely to have coronary artery disease, hypertension, diabetes, and renal dysfunction. During a median follow-up duration of 247 days (IQR 96-480 days), the detection of increased cTnT levels was associated with a higher rate of all-cause deaths and, for cTnT release, all-cause death and cardiovascular rehospitalisation rate. CTnT release was an independent predictor of all-cause death and cardiovascular rehospitalisation, along with glomerular filtration rate, and the administration of inotropic agents during the initial hospitalisation. CONCLUSIONS: Increased cTnT levels are a frequent finding in patients with AHF. They are more likely to occur in patients with comorbidities and are associated with poorer outcomes. cTnT release is an independent predictor of poorer outcomes.

Cardiovascular mortality in dialysis patients.

In their broad spectrum, cardiovascular diseases are, collectively, the major cause of death in patients on dialysis. The population of patients treated with peritoneal dialysis and hemodialysis are not only subject to the traditional risk factors for heart disease, but also to certain uremia-associated risk factors that are unique in this population. In the dialysis population, data regarding the effectiveness of routine pharmacologic and procedural interventions on cardiovascular outcomes are limited. Most dialysis patients are excluded from clinical trials, and so data from randomized controlled trials investigating outcomes in patients undergoing peritoneal dialysis or hemodialysis are almost absent. In this review, we discuss some of the major cardiovascular problems in the dialysis population, the impact of those problems on survival, and when data are available, the impact of therapeutic strategies.

Increasing benefit from revascularization is associated with increasing amounts of myocardial hibernation: a substudy of the PARR-2 trial.

OBJECTIVES: We sought to determine: 1) whether F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) parameters identify high-risk patients who gain benefit from revascularization; 2) whether there is a cut point for such benefit; and 3) predictors of outcome in patients with severe left ventricular (LV) dysfunction due to coronary artery disease. BACKGROUND: Patients with ischemic LV dysfunction might benefit from revascularization but not without risk. The FDG PET imaging can detect viable myocardium that recovers after revascularization. In the PARR-2 (PET and Recovery Following Revascularization-2) trial, FDG PET imaging showed a nonsignificant trend for improved outcome compared with standard care. Understanding the predictors of outcome from this prospective trial should help better identify patients at risk and which patients most benefit from revascularization. METHODS: This post hoc analysis included 182 patients with left ventricular ejection fraction (LVEF) <35% and coronary artery disease, being considered for revascularization work-up, and randomized to the PET arm of PARR-2. The primary outcome was a composite of cardiac death, myocardial infarction, or cardiac repeat hospital stay at 1 year. RESULTS: There is an interaction between PET mismatch and protocol revascularization such that higher mismatch, when combined with revascularization, yields fewer primary outcome events (p = 0.02). On the basis of adjusted Cox modeling, with reduced mismatch (<7%), the risk is not significantly different with or without revascularization. As mismatch increases above this mark, risk is reduced with revascularization. Increasing creatinine (for a 10-mumol/l increase: hazard ratio: 1.03, 95% confidence interval: 1.01 to 1.06, p = 0.010) is also associated with increased risk, whereas decreasing LVEF (for a 2% decrease: hazard ratio: 1.08, 95% confidence interval: 0.99 to 1.18, p = 0.087) trends toward an association with increased risk. CONCLUSIONS: In this post hoc analysis, patients with ischemic cardiomyopathy with larger amounts of mismatch have improved outcome with revascularization. Renal function was also an independent predictor of outcome. The FDG PET seems to define high-risk patients that gain benefit from revascularization. (PET and Recovery Following Revascularization [PARR 2]; NCT00385242).

Hemodialysis-induced cardiac injury: determinants and associated outcomes.

BACKGROUND AND OBJECTIVES: Hemodialysis (HD)-induced myocardial stunning driven by ischemia is a recognized complication of HD, which can be ameliorated by HD techniques that improve hemodynamics. In nondialysis patients, repeated ischemia leads to chronic reduction in left ventricular (LV) function. HD may initiate and drive the same process. In this study, we examined the prevalence and associations of HD-induced repetitive myocardial injury and long-term effects on LV function and patient outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Seventy prevalent HD patients were assessed for evidence of subclinical myocardial injury at baseline using serial echocardiography and followed up after 12 mo. Intradialytic blood pressure, hematologic and biochemical samples, and patient demographics were also collected at both time points. RESULTS: Sixty-four percent of patients had significant myocardial stunning during HD. Age, ultrafiltration volumes, intradialytic hypotension, and cardiac troponin-T (cTnT) levels were independent determinants associated with its presence. Myocardial stunning was associated with increased relative mortality at 12 mo (P = 0.019). Cox regression analysis showed increased hazard of death in patients with myocardial stunning and elevated cTnT than in patients with elevated cTnT alone (P < 0.02). Patients with myocardial stunning who survived 12 mo had significantly lower LV ejection fractions at rest and on HD (P < 0.001). CONCLUSIONS: HD-induced myocardial stunning is common, and may contribute to the development of heart failure and increased mortality in HD patients. Enhanced understanding of dialysis-induced cardiac injury may provide novel therapeutic targets to reduce currently excessive rates of cardiovascular morbidity and mortality.

Early intra-aortic balloon pumping following perioperative myocardial injury improves hospital and mid-term prognosis.

We evaluated the impact of immediate intra-aortic balloon pumping (IABP) on hospital and mid-term outcome of coronary artery bypass graft (CABG) whenever perioperative acute complications developed. We compared clinical, biochemical, echocardiographic in-hospital results and two-year follow-up outcome of 30 low-risk (EuroSCORE<5) CABG (group A) who immediately received perioperative IABP when acute complications were suspected, to a contemporary, uncomplicated case-matched group (30 patients; Group B). Two in-hospital deaths were recorded in group A with no deaths in controls (P=0.492). Group A showed significantly higher lactate only at ICU arrival (P=0.001). Troponin I was always higher, but never reached values diagnostic for myocardial infarction (P<0.001). Worse left ventricular ejection fraction (P<0.001) and wall motion score index (P=0.008) were recorded at ICU arrival in group A, although an almost complete recovery was registered at discharge. Two-year actuarial survival was similar between the two groups (P=0.598). No differences were observed in freedom from acute myocardial infarction (P=0.503) and from overall cardiac complications (P=0.410). Early IABP should be established whenever cardiac complications are suspected, because of its beneficial impact on enzymatic leakage, myocardial recovery at echocardiography, hospital outcome, mid-term follow-up survival and freedom from cardiovascular events.

[Chronic ischemic heart failure. Revascularization improves survival among patients with hibernating myocardium]. / Kronisk iskaemisk hjerteinsufficiens. Revaskularisering bedrer overlevelsen blandt patienter med hibernating myocardium.

INTRODUCTION: Patients with ischemic heart failure and reversible dysfunctional myocardium (Hibernating myocardium, HIB) can benefit from revascularization. These patients can be selected with nuclear methods. The purpose of this study was to describe the results of the imaging procedures in patients tested for HIB and relate the results to the choice of treatment and cause of death. MATERIALS AND METHODS: During a 2-year period 51 patients were referred to determine the amount of HIB. This can be determined with blood flow and metabolic imaging of the heart. Resting-myocardial perfusion imaging was performed with 99mTc-sestamibi and glucose metabolism was visualized with 18F-fluorodeoxyglucose (18F-FDG) gamma camera PET. Medical records and death certificate were reviewed retrospectively. RESULTS: 50 patients were included. We found an increased survival among patients with HIB who underwent revascularization (1 year mortality 6% vs. 33%, p = 0,004). Patients with HIB who did not undergo revascularization had an increased risk of sudden death. (5/15 patients vs. 0/35 patients, p = 0,003). CONCLUSION: Despite a simplified method we find the same increased mortality among medically-treated patients with HIB as in earlier studies. This and earlier studies are all retrospective with the risk of selection bias. Prospective studies are underway. Nuclear imaging is useful in evaluating patients with heart failure before revascularization.

[Levosimendan in cardiology and intensive care medicine]. / Levosimendan in Kardiologie und Intensivmedizin.

Levosimendan (LS) is a new calcium sensitizer that exerts positive inotropic effects without increasing intracellular cAMP or Ca2+ at therapeutic doses and therefore may avoid major limitations of beta-adrenergic agents. LS also causes arteriolar and venous dilation by opening potassium channels on vascular smooth muscle cells. In addition, LS does not increase myocardial oxygen demand and may exert anti-stunning effects. LS itself has a short elimination half life but has shown to have active metabolites with elimination half lives up to 80 hours. Three hemodynamic studies show that at recommended doses LS increases cardiac output by 8-30% and reduces pulmonary capillary wedge pressure by 11-28% in heart failure patients. Systemic vascular resistance falls significantly and blood pressure tends to decline. The hemodynamic effects are not attenuated by concomitant beta-blocker medication. Two large randomized studies on patients with chronic and acute congestive heart failure found a decrease in mortality with LS. In the LIDO trial there was a 52.9% survival benefit at day 31 when compared with patients receiving dobutamine. In the RUSSLAN trial, the survival benefit approached 40% at day 14 after start of treatment compared to placebo. Experience in the ICU setting is limited but LS therapy in postoperative low output failure and cardiogenic shock seems to be feasible and LS is a promising agent in the inotropic armamentarium. LS has a favourable side effect profile and is approved for 24-hour use in congestive heart failure. It may cause hypotension due to vasodilation, and this effect may be aggravated by inadequate preload conditions. Further morbidity and mortality studies are required to confirm the encouraging data from the LIDO and RUSSLAN trial but already the existing data support LS as the inotropic agent of choice in patients with worsening heart failure and a systolic arterial blood pressure beyond 90 mmHg.