Serum neprilysin levels are associated with myocardial stunning after ST-elevation myocardial infarction.

BACKGROUND: Left ventricular remodeling following ST-elevation myocardial infarction (STEMI) is associated with poor outcome, including heart failure (HF). Neprilysin inhibition leads to improved outcome in patients with altered left ventricular ejection fraction (LVEF). METHODS: We aimed to assess the association between serum levels of neprilysin and left ventricular (LV) volumes, function and remodeling in STEMI patients with successful myocardial reperfusion and no clinical sign of HF. Sixty-eight patients were admitted for STEMI and had both plasma neprilysin measurement at baseline and 3D transthoracic echocardiogram at baseline and after a median follow-up of 7 months. We compared 3 groups: a group with a low-level of plasma neprilysin (< 125 pg/mL, i.e. the lower limit of detection of the assay) and the two other groups were defined as being below or above the median value of the remaining samples. RESULTS: Median age was 58.5 ± 12.8 years and 56 (82.4%) were men. Median LVEF was 45.0 ± 8.5%. Baseline characteristics were comparable between groups (low-level of neprilysin group [≤125 pg/mL, n = 38], medium-level of neprilysin group [126-450 pg/mL, n = 15] and a high-level group [> 450 pg/mL, n = 15]). At baseline there was a non-significant trend towards lower end-diastolic volume (p = 0.07) but significantly lower LVEF in the high neprilysin group (46.4 ± 8.3%, 47.1 ± 8.1% and 39.1 ± 6.9%, p < 0.01). At follow-up, the magnitude of LVEF increase was significantly more important in the high neprilysin group compared to the other groups (p = 0.022 for relative change in LVEF and 6.6 ± 7.3%, 3.6 ± 9.0% and 11.3 ± 8.4%, p = 0.031 for absolute change in LVEF) resulting in similar LVEF levels at follow-up between all groups (53.0 ± 8.9%, 50.6 ± 9.7% and 50.4 ± 9.9%, p = 0.55). CONCLUSIONS: Initial high neprilysin levels may identify patients with stunned myocardium early after STEMI, with a recovery of contractility leading to improved LVEF at follow-up. Future studies will have to assess the role of neprilysin in the setting of STEMI and the potential benefit of its blockade.

Myocardial ischemia: lack of coronary blood flow, myocardial oxygen supply-demand imbalance, or what?

This opinionated article reviews current concepts of myocardial ischemia. Specifically, the historical background is briefly presented. Then, the prevailing paradigm of myocardial oxygen-supply-demand imbalance is criticized since demand is a virtual parameter that cannot be measured and data on measurements of myocardial blood flow and contractile function rather support matching between flow and function. Finally, a concept of myocardial ischemia that focusses on the reduction of coronary blood flow to below 8-10 µl/g per beat with consequences for myocardial electrical, metabolic, contractile and morphological features is advocated.

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.

Brain-Heart Interactions in Traumatic Brain Injury.

The cardiovascular manifestations associated with nontraumatic head disorders are commonly known. Similar manifestations have been reported in patients with traumatic brain injury (TBI); however, the underlying mechanisms and impact on the patient's clinical outcomes are not well explored. The neurocardiac axis theory and neurogenic stunned myocardium phenomenon could partly explain the brain-heart link and interactions and can thus pave the way to a better understanding and management of TBI. Several observational retrospective studies have shown a promising role for beta-adrenergic blockers in patients with TBI in reducing the overall TBI-related mortality. However, several questions remain to be answered in clinical randomized-controlled trials, including population selection, beta blocker type, dosage, timing, and duration of therapy, while maintaining the optimal mean arterial pressure and cerebral perfusion pressure in patients with TBI.

Radiofrequency catheter ablation versus balloon cryoablation of atrial fibrillation: markers of myocardial damage, inflammation, and thrombogenesis.

BACKGROUND: Evidence from animal and human studies suggests that cryoablation might be associated with a lesser inflammatory response and activation of coagulation compared with radiofrequency ablation. The study was aimed at comparing the effect of cryoballoon and radiofrequency catheter ablation of paroxysmal atrial fibrillation on markers of myocardial damage, inflammation, and activation of coagulation. METHODS: Forty-one patients received either cryoballoon (n = 23) or radiofrequency (n = 18) ablation of atrial fibrillation. We measured troponin I, high-sensitivity CRP, and interleukin 6 at baseline from the cubital vein, and from the right and left atrium before and after ablation, and from the cubital vein the following day. Prothrombin fragments 1 + 2, soluble P­selectin, and D­dimer were measured before and after ablation from both atria. RESULTS: We observed higher troponin I release in the cryoballoon than in the radiofrequency group (7.01 mcg/l (interquartile range [IQR]: 5.30-9.09) vs 2.32 mcg/l (IQR: 1.45-2.98), p < 0.001). The levels of inflammatory markers (high-sensitivity CRP and interleukin 6) in the two groups were comparable, as were the levels of markers of coagulation activation. Procedure duration, fluoroscopy times, and mid-term success (23 months, IQR 7-32) of the two groups were also comparable. CONCLUSIONS: Cryoballoon ablation of atrial fibrillation causes more significant myocardial damage, that is, more extensive ablation lesions, compared with radiofrequency catheter ablation. However, no major differences between these two ablation techniques with regard to the inflammatory response and activation of the coagulation system were observed.

Thyroid hormone and the stunned myocardium.

Acute critically ill patients experience a rapid decline in plasma free thyroid hormone levels (free triiodothyronine (FT3) and free levothyroxine (FT4)), with a marked elevation of reverse T3, recognized as the euthyroid sick syndrome (ESS) or low-T3 syndrome. The ESS is also often associated with depressed myocardial function, sometimes referred to as the 'stunned myocardium'. Its clinical effects may vary from minimal hemodynamic impairment to cardiogenic shock. Medical management may range from aspirin alone to placement of a left ventricular assist device. With adequate supportive therapy, recovery usually occurs within days or weeks. The effect of T3/T4 therapy has been studied in three conditions in which the ESS and myocardial functional depression have been documented - i) transient regional myocardial ischemia and reperfusion, ii) transient global myocardial ischemia in patients undergoing cardiac surgery on cardiopulmonary bypass, and iii) transient inadequate global myocardial perfusion in brain-dead potential organ donors. Under all three conditions, myocardial ischemia leads to rapid loss of high-energy phosphates, accumulation of myocardial tissue lactate, and probably loss of homeostasis of cytosolic calcium, which may further increase cell injury. There is an inability to generate ATP through the Krebs cycle, which reduces the high-energy phosphate pool essential for all cell ATPases. Under all three conditions, following administration of T3/T4, the myocardial dysfunction was rapidly reversed. We, therefore, cautiously advocate the use of thyroid hormonal therapy to any patient with the ESS and/or a stunned myocardium.

Enhancement of myocardial function and reduction of injury with levosimendan after percutaneous coronary intervention for acute myocardial infarction: a pilot study.

OBJECTIVES: To determine the short-term clinical effects of levosimendan in acute myocardial infarction (AMI) patients with myocardial stunning after emergency percutaneous coronary intervention (PCI). METHODS: The study population consisted of 30 patients with AMI who received emergency PCI and satisfied the inclusion criteria. Levosimendan was given as a continuous infusion of 0.1 µg/kg/min for 24 h, and the remaining 10 patients received placebo treatment. The patients were observed with invasive haemodynamic monitoring and were evaluated biochemically and echocardiographically before and after the drug infusion. RESULTS: Following treatment, biochemical indices (not including creatine kinase and its MB fraction) were significantly lower in the levosimendan group than in the placebo group. Meanwhile, left-ventricular (LV) end-systolic volume, mean pulmonary arterial pressure, pulmonary capillary wedge pressure and systemic vascular resistance were significantly reduced in the levosimendan group, whereas the early-to-late diastolic velocities ratio, LV ejection fraction, cardiac index and cardiac power index were increased. Troponin I levels were reduced and fewer stunned and infarction segments were observed in the patients treated with levosimendan. CONCLUSIONS: Levosimendan can significantly improve the myocardium function of patients with myocardial stunning after PCI.

First evidence of increased plasma serotonin levels in Tako-Tsubo cardiomyopathy.

BACKGROUND: There is no data about the serotonergic activity during the acute phase of Tako-Tsubo Cardiomyopathy (TTC). The objective of our study was to investigate evidence of serotonin release from patients with TTC in comparison with patients with ST elevation myocardial infarction (STEMI) and healthy control subjects (HCS). METHODS AND RESULTS: Plasma serotonin levels in 14 consecutive patients with TTC were compared with those in 14 patients with STEMI and 14 HCS. Plasma serotonin levels at admission were markedly higher in patients with TTC and STEMI as compared to HCS (3.9 ± 4.6, P = 0.02 versus control; 5.7 ± 5.6, P = 0.001 versus control; and 1 ± 0.4 ng/mL, resp.). There was no difference in serotonin levels between patients with TTC and those with STEMI (P = 0.33). CONCLUSION: This finding suggests that serotonin could participate to the pathophysiology of TTC.

N-terminal Pro-B-type natriuretic peptide and its correlation to haemodialysis-induced myocardial stunning.

BACKGROUND: Haemodialysis (HD) is able to induce recurrent myocardial ischemia and segmental left-ventricular dysfunction (myocardial stunning). The association of N-terminal Pro-B-type natriuretic peptide (NTpro-BNP) with HD-induced myocardial stunning is unclear. METHODS: In 70 prevalent HD patients, HD-induced myocardial stunning was assessed echocardiographically at baseline and after 12 months. The extent to which pre-dialysis NTpro-BNP was associated with the occurrence of HD-induced myocardial stunning was assessed as the primary endpoint. RESULTS: The median Ntpro-BNP concentration in this cohort was 2,154 pg/ml (IQR 1,224-3,014). Patients experiencing HD-induced myocardial stunning at either time point displayed elevated NTpro-BNP values (2,418 pg/ml, IQR, 1,583-3,474 vs. 1,751 pg/ml, IQR (536-2,029), p = 0.02). NTpro-BNP levels did not differ between patients showing HD-induced stunning at baseline and those developing stunning during the observational period (p = 0.8). NTpro-BNP levels drawn at the beginning of the dialysis session achieved a poor diagnostic accuracy for the detection of myocardial stunning (area under the ROC curve 0.61, 95% CI 0.45-0.77), but provided an accurate rule out for myocardial stunning during the subsequent year (AUC 0.85, 95% CI 0.70-0.99). The calculated cut-off of 1,570 pg/ml achieved a sensitivity of 66% and a specificity of 78% for the exclusion of myocardial stunning at any time point. In logistic regression analysis, only low NTpro-BNP levels (OR 0.92 for every additional 100 pg/ml, 95% CI 0.85-0.99, p = 0.03) were significantly associated with absence of myocardial stunning at any time point. CONCLUSION: Predialytic NTpro-BNP levels fail to adequately diagnose current dialysis-induced myocardial stunning, but help to identify patients with a propensity to develop dialysis-induced myocardial stunning at any time during the next 12 months.

Increased H-FABP concentrations in nonalcoholic fatty liver disease. Possible marker for subclinical myocardial damage and subclinical atherosclerosis.

AIM: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder which is reported as the hepatic manifestation of metabolic syndrome with an increased risk of cardiovascular events. Patients with NAFLD are also at risk of future cardiac events independently of metabolic syndrome. The aim of this study was to examine serum concentrations of heart type fatty acid binding protein (H-FABP) in NAFLD and to investigate its correlations with metabolic parameters and subclinical atherosclerosis. PATIENTS AND METHODS: A total of 34 patients with NAFLD and 35 healthy subjects were enrolled in the study. NAFLD patients had elevated liver enzymes and steatosis graded on ultrasonography. Healthy subjects had normal liver enzymes and no steatosis on ultrasonography. H-FABP levels were measured using an enzyme linked immunosorbent assay (ELISA) method and correlations with metabolic parameters and subclinical atherosclerosis were examined. Subclinical atherosclerosis was determined with carotid artery intima-media thickness (CIMT) which was measured by high resolution B mode ultrasonography. RESULTS: H-FABP levels were elevated in patients with NAFLD (16.3 ± 4.0 ng/ml) when compared with healthy controls (13.8 ± 2.1 ng/ml; p < 0.001). NAFLD patients had significantly higher CIMT than the controls had (0.64 ± 0.17 mm vs. 0.43 ± 0.14 mm, p = 0.009). The H-FABP concentrations were significantly positively correlated with body mass index (r = 0.255, p = 0.042), fasting blood glucose level (r = 0.300, p = 0.013), CIMT (r = 0.335, p = 0.043), and homeostasis model assessment-estimated insulin resistance (HOMA-IR; r = 0.156, p = 0.306). In multiple linear regression analysis, H-FABP levels were only independently associated with CIMT (p = 0.04) CONCLUSION: Serum H-FABP concentrations increase in patients with NAFLD. Our results may not only suggest that H-FABP is a marker of subclinical myocardial damage in patients with NAFLD but also of subclinical atherosclerosis, independent of metabolic syndrome and cardiac risk factors.

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.

Comparative determination and monitoring of biomarkers of necrosis and myocardial remodeling between radiofrequency ablation and cryoablation.

BACKGROUND: Biomarkers of necrosis and inflammation have been found raised after radiofrequency ablation (RF). There is scarce information on biomarkers' behavior after cryoablation. Our aim was to study biomarkers of necrosis, inflammation, and interstitial remodeling after two different approaches: RF versus cryoablation. METHODS: We studied 22 consecutive patients with atrial flutter who underwent RF (10) or cryoablation (12). All patients underwent electrophysiological study and subsequent ablation. Peripheral samples were collected before the procedure, immediately after, the following day, 3 days, 1 week, 1 month, and 2 months after ablation. Samples were assayed for biomarkers of inflammation (high sensitive C-reactive protein [hs-CRP]) and tissue remodeling (C-propeptide of type I procollagen [CICP], matrix metalloproteinase 2 [MMP-2], matrix metalloproteinase 9 [MMP-9], and metallopeptidase inhibitor 1 [TIMP-1]). We also determined biomarkers of tissue necrosis (creatine kinase [CK], its MB isoenzyme, cardiac troponin I [TnI], and troponin T (TnT)] in samples obtained immediately after ablation, 6 hours postablation, and 12 hours postablation. RESULTS: Bidirectional isthmus block was achieved in all patients. We found significantly higher levels of CK, CK-MB, and TnI after cryoablation compared to RF ablation for all timing samples. These necrosis biomarkers showed significant differences depending on the time (all P < 0.001), and the interaction between the time and the used ablation approach (P = 0.005, P < 0.001, and P < 0.001, respectively). For patients who undergoing RF ablation, MMP-2 showed the greatest changes depending on the interaction between time and number of applications (P = 0.041), whereas for patients who undergoing cryoablation, CK was the most relevant biomarker depending on the interaction between time and number of applications (P = 0.006). CONCLUSIONS: We show higher levels of necrosis and myocardial injury biomarker after cryoablation versus RF. However, we found higher remodeling processes after RF. Our data support previous publications showing different lesion formation in cryoablation and RF.

Troponin T for the detection of dialysis-induced myocardial stunning in hemodialysis patients.

BACKGROUND AND OBJECTIVES: Circulating troponin T levels are frequently elevated in patients undergoing long-term dialysis. The pathophysiology underlying these elevations is controversial. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In 70 prevalent hemodialysis (HD) patients, HD-induced myocardial stunning was assessed echocardiographically at baseline and after 12 months. Nineteen patients were not available for the follow-up analysis. The extent to which predialysis troponin T was associated with the occurrence of HD-induced myocardial stunning was assessed as the primary endpoint. RESULTS: The median troponin T level in this hemodialysis cohort was 0.06 ng/ml (interquartile range, 0.02-0.10). At baseline, 64% of patients experienced myocardial stunning. These patients showed significantly higher troponin T levels than patients without stunning (0.08 ng/ml [0.05-0.12] versus 0.02 ng/ml [0.01-0.05]). Troponin T levels were significantly correlated to measures of myocardial stunning severity (number of affected segments: r=0.42; change in ejection fraction from beginning of dialysis to end of dialysis: r=-0.45). In receiver-operating characteristic analyses, predialytic troponin T achieved an area under the curve of 0.82 for the detection of myocardial stunning. In multivariable analysis, only ultrafiltration volume (odds ratio, 4.38 for every additional liter) and troponin T (odds ratio, 9.33 for every additional 0.1 ng/ml) were independently associated with myocardial stunning. After 12 months, nine patients had newly developed myocardial stunning and showed a significant increase in troponin T over baseline (0.03 ng/ml at baseline versus 0.05 ng/ml at year 1). CONCLUSIONS: Troponin T levels in HD patients are associated with the presence and severity of HD-induced myocardial stunning.

Direct protective effects of dexmedetomidine against myocardial ischemia-reperfusion injury in anesthetized pigs.

Systemic administration of α2-adrenergic agonists has been shown to protect ischemic myocardium, but the direct effects on ischemia-reperfused myocardium have not yet been clarified. This study was carried out to determine the effects of intracoronary dexmedetomidine (DEX) on the myocardial ischemia-reperfusion injury in anesthetized pigs. In open-chest pigs, the left anterior descending coronary artery was perfused through an extracorporeal circuit from the carotid artery. They received intracoronary infusion of DEX at a rate of 1 ng · mL(-1) (group LD, n = 9), 10 ng · mL(-1) (group MD, n = 9), or 100 ng · mL(-1) (group HD, n = 9) of coronary blood flow or vehicle (group C, n = 12) for 30 min before ischemia. Myocardial stunning was produced by 12-min ischemia of the perfused area of left anterior descending coronary artery and 90-min reperfusion. The effect on reperfusion-induced arrhythmias was evaluated using the incidence of ventricular tachycardia or fibrillation after reperfusion. Regional myocardial contractility was evaluated with segment shortening (%SS). Dexmedetomidine significantly reduced the incidence of reperfusion-induced ventricular arrhythmias. Dexmedetomidine significantly improved the recovery of percentage segment shortening at 90 min after reperfusion (32.6% ± 3.1% in group C, 58.2% ± 2.1% in group LD, 61.1% ± 1.8% in group MD, and 72.0% ± 2.0% in group HD). Dexmedetomidine suppressed the increase in plasma norepinephrine concentration after reperfusion. The results indicate that DEX would exert the protective effect against ischemia-reperfusion injury by the direct action on the myocardium, which is not mediated through the central nervous system.

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.

Near-fatal tramadol cardiotoxicity in a CYP2D6 ultrarapid metabolizer.

BACKGROUND: Tramadol is a synthetic, centrally acting analgesic for the treatment of moderate to severe pain. The marketed tramadol is a racemic mixture containing 50% (+)tramadol and 50% (-)tramadol and is mainly metabolized to O-desmethyltramadol (M1) by the cytochrome P450 CYP2D6. Tramadol is generally considered to be devoid of any serious adverse effects of traditional opioid receptor agonists, such as respiratory depression and drug dependence. CASE REPORT: A 22-year-old Caucasian female patient was admitted to our ICU in refractory cardiac arrest requiring extracorporeal membrane oxygenation. This aggressive support allowed resolution of multi-organ dysfunction syndrome. Repeated blood analyses using liquid chromatography-tandem mass spectrometry confirmed high concentrations of both tramadol and its main metabolite O-desmethyltramadol. Genotyping of CYP2D6 revealed the patient to be heterozygous for a duplicated wild-type allele, predictive of a CYP2D6 ultrarapid metabolizer (UM) phenotype, confirmed by calculation of the tramadol/M1 (MR1) metabolic ratio at all time points. DISCUSSION: We here report a case of near-fatal isolated tramadol cardiotoxicity. Because of the inhibition of norepinephrine reuptake, excessive blood epinephrine levels in this CYP2D6R UM patient following excessive tramadol ingestion could explain the observed strong myocardial stunning. This patient admitted intermittent tramadol consumption to gain a "high" sensation. In patients with excessive morphinomimetic effects, levels of tramadol and its main metabolite M1could be measured, ideally combined with CYP2D6 genotyping, to identify individuals at risk of tramadol-related cardiotoxicity. Tramadol treatment could be optimized in these at-risk individuals, consequently improving patient outcome and safety.

Frequent hemodialysis schedules are associated with reduced levels of dialysis-induced cardiac injury (myocardial stunning).

BACKGROUND AND OBJECTIVES: Recurrent hemodialysis (HD)-induced ischemic cardiac injury (myocardial stunning) is common and associated with high ultrafiltration (UF) requirements, intradialytic hypotension, long-term loss of systolic function, increased likelihood of cardiovascular events, and death. More frequent HD regimens are associated with lower UF requirements and improved hemodynamic tolerability, improved cardiovascular outcomes, and reduced mortality compared with conventional thrice-weekly HD. This study investigated the hypothesis that modification of UF volume and rate with more frequent HD therapies would abrogate dialysis-induced myocardial stunning. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS: A cross-sectional study of 46 patients established on hemodialysis >3 months compared four groups receiving the current range of quotidian therapies: conventional thrice-weekly HD (CHD3); more-frequent HD five to six times/week in a center (CSD) and at home (HSD); and home nocturnal HD (HN). Serial echocardiography quantitatively assessed regional systolic function to identify intradialytic left ventricular regional wall motion abnormalities (RWMAs). Cardiac troponin T (cTnT), N-terminal prohormone brain natriuretic peptide (NT-proBNP), and inflammatory markers were quantified. RESULTS: More frequent HD regimens were associated with lower UF volumes and rates compared with CHD3. Intradialytic fall in systolic BP was reduced in CSD and HSD groups and abolished in HN group. Mean RWMAs per patient reduced with increasing dialysis intensity (CHD3 > CSD > HSD > HN). Home-based groups demonstrated lower high-sensitivity C-reative protein levels, with trends to lower cTnT and NT-proBNP levels in the more frequent groups. CONCLUSIONS: Frequent HD regimes are associated with less dialysis-induced myocardial stunning compared with conventional HD. This may contribute to improved outcomes associated with frequent HD therapies.

Higher arteriovenous fistulae blood flows are associated with a lower level of dialysis-induced cardiac injury.

Native arteriovenous fistulae (AVF) remain the vascular access of choice for hemodialysis (HD). Despite being associated with superior long-term outcomes (cf. catheter use), little is known about the systemic hemodynamic consequences of AVFs. Repetitive myocardial injury (myocardial stunning) is an under-recognized common consequence of HD. The aim of this study was to examine the impact of AVF flow (Qa) on dialysis-induced cardiac injury. We studied 50 chronic HD patients. All patients underwent echocardiography (and subsequent quantitative offline analysis) at baseline, during and post dialysis, to assess left ventricular function and the development of regional wall motion abnormalities. Qa was measured using ionic dialysance. Patients were divided into Qa tertiles (<500, mean 291+/-101 mL/min, 500-1000, mean 739+/-130 mL/min and >1000, mean 1265+/-221 mL/min). There were no significant differences between the groups in terms of age, sex, diabetes, or resting ejection fraction. Patients with Qa>1000 mL/min had a lower prevalence of left ventricular hypertrophy (55% vs. 76%, P=0.01). Dialysis-induced myocardial stunning (seen in 65% of the patients studied) was significantly and sequentially reduced in those patients with higher Qas. This was seen in a lower number of segments and ventricular regions developing regional wall motion abnormalities, as well as a significantly reduced mean and cumulative percentage reduction in fractional shortening of those ventricular segments affected (-187+/-37%, -161+/-26%, and -101+/-25%, respectively, P=0.04). Relatively higher AVF flows appear to be associated with a lower level of observed HD-induced cardiac injury.