Prognostic value of admission serum magnesium in acute myocardial infarction complicated by malignant ventricular arrhythmias.

OBJECTIVES: Although electrolyte abnormalities are related to worse clinical outcomes in patients with acute myocardial infarction (AMI), little is known about the association between admission serum magnesium level and adverse events in AMI patients complicated by out-of-hospital cardiac arrest presenting with malignant ventricular arrhythmias (OHCA-MVA). We investigated the prognostic value of serum magnesium level on admission in these patients. METHODS: We retrospectively analyzed the data of 165 consecutive reperfused AMI patients complicated with OHCA-MVA between April 2007 and February 2020 in our university hospital. Serum magnesium concentration was measured on admission. The primary outcome was in-hospital death. RESULTS: Fifty-four patients (33%) died during hospitalization. Higher serum magnesium level was significantly related to in-hospital death (Fine & Gray's test; p < 0.001). In multivariable logistic regression analyses, serum magnesium level on admission was independently associated with in-hospital death (hazard ratio 2.68, 95% confidence interval 1.24-5.80) even after adjustment for covariates. Furthermore, the incidences of cardiogenic shock necessitating an intra-aortic balloon pump (p = 0.005) or extracorporeal membrane oxygenation (p < 0.001), tracheal intubation (p < 0.001) and persistent vegetative state (p = 0.002) were significantly higher in patients with higher serum magnesium level than in those with lower serum magnesium level. CONCLUSIONS: In reperfused AMI patients complicated by OHCA-MVA, admission serum magnesium level might be a potential surrogate marker for predicting in-hospital death.

Near-infrared spectroscopy after out-of-hospital cardiac arrest.

BACKGROUND: Cerebral hypoperfusion may aggravate neurological damage after cardiac arrest. Near-infrared spectroscopy (NIRS) provides information on cerebral oxygenation but its relevance during post-resuscitation care is undefined. We investigated whether cerebral oxygen saturation (rSO2) measured with NIRS correlates with the serum concentration of neuron-specific enolase (NSE), a marker of neurological injury, and with clinical outcome in out-of-hospital cardiac arrest (OHCA) patients. METHODS: We performed a post hoc analysis of a randomised clinical trial (COMACARE, NCT02698917) comparing two different levels of carbon dioxide, oxygen and arterial pressure after resuscitation from OHCA with ventricular fibrillation as the initial rhythm. We measured rSO2 in 118 OHCA patients with NIRS during the first 36 h of intensive care. We determined the NSE concentrations from serum samples at 48 h after cardiac arrest and assessed neurological outcome with the Cerebral Performance Category (CPC) scale at 6 months. We evaluated the association between rSO2 and serum NSE concentrations and the association between rSO2 and good (CPC 1-2) and poor (CPC 3-5) neurological outcome. RESULTS: The median (inter-quartile range (IQR)) NSE concentration at 48 h was 17.5 (13.4-25.0) µg/l in patients with good neurological outcome and 35.2 (22.6-95.8) µg/l in those with poor outcome, p < 0.001. We found no significant correlation between median rSO2 and NSE at 48 h, rs = - 0.08, p = 0.392. The median (IQR) rSO2 during the first 36 h of intensive care was 70.0% (63.5-77.0%) in patients with good outcome and 71.8% (63.3-74.0%) in patients with poor outcome, p = 0.943. There was no significant association between rSO2 over time and neurological outcome. In a binary logistic regression model, rSO2 was not a statistically significant predictor of good neurological outcome (odds ratio 0.99, 95% confidence interval 0.94-1.04, p = 0.635). CONCLUSIONS: We found no association between cerebral oxygenation measured with NIRS and NSE concentrations or outcome in patients resuscitated from OHCA. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02698917 . Registered on 26 January 2016.

In-Hospital Electrical Storm in Acute Myocardial Infarction　- Clinical Background and Mechanism of the Electrical Instability.

BACKGROUND: Recurrent ventricular tachycardia (VT) and fibrillation (VF), the so-called "electrical storm" (ES) occurs at various stages of acute myocardial infarction (AMI), but its incidence, background, and short-term prognosis remain unclear. Methods and Results: A retrospective observational study was performed using the registry database of the Tokyo CCU Network. The individual data of 6,003 patients with AMI during 2011-2012 was corrected. ES was defined as more than 3 episodes of sustained VT/VF during a 24-h period as first documented after hospitalization. ES occurred in 55 patients after admission (0.9%). The ES(+) group had more severe heart failure (Killip class >III), more extensive MI (peak-CK), greater inflammatory reaction (CRP), history of diabetes, and more frequent application of hemodialysis as compared with the ES(-) group (n=5,865). When the ES patients were divided into Early-ES (n=37: ES occurred ≤48 h after the onset of MI) and Late-ES (n=15 >48 h after onset of MI) groups, logistic regression analysis revealed that Early-ES was associated with severity of MI, whereas Late-ES was related to systemic disorders, including inflammation, renal dysfunction, or diabetes. Late-ES was an independent predictor of in-hospital death. CONCLUSIONS: In-hospital ES was a rare clinical manifestation of AMI. The features and background of the ES varied as time elapsed after admission for MI.

Renal denervation decreases susceptibility of the heart to ventricular fibrillation in a canine model of chronic kidney disease.

NEW FINDINGS: What is the central question of this study? Renal denervation (RDN) has been shown to be effective and safe, resulting in better control of blood pressure and an improvement in left ventricular hypertrophy in chronic kidney disease (CKD) patients. Ventricular arrhythmias and sudden cardiac death are common causes of death in CKD patients, but previous studies pay almost no attention to the effects of RDN on the risk of ventricular fibrillation associated with CKD. What is the main finding and its importance? Renal denervation could decrease susceptibility of the heart to ventricular fibrillation in a canine CKD model. Improvement of left ventricular hypertrophy, sympathetic activation and inflammation by RDN may be responsible for its beneficial effects. Renal denervation (RDN) has been shown to have therapeutic value in patients with chronic kidney disease (CKD). The aim of this study was to investigate whether RDN could decrease the susceptibility of the heart to ventricular fibrillation in a canine model of CKD. Twenty-one dogs were used. Chronic kidney disease was produced by subtotal nephrectomy in 16 dogs with RDN treatment (CKD + RDN group, n = 8) or sham RDN (CKD group, n = 8). Another five dogs underwent sham operation and sham RDN to serve as controls (CTR group). Parameters of renal function, blood pressure, echocardiography, ECG, noradrenaline and inflammation were measured at baseline and 6 weeks after the surgical procedure. The ventricular fibrillation threshold (VFT) was determined at the end of the study. Subtotal nephrectomy successfully induced a canine CKD model. When compared with the CTR group, subtotal nephrectomy in the CKD group significantly elevated blood pressure; increased the left ventricular mass, end-diastolic left ventricular internal dimension, left ventricular end-diastolic posterior wall thickness and end-diastolic interventricular septum thickness; prolonged the QT interval, corrected QT interval, the interval from the peak to the end of the T wave (Tp-e) and the corrected Tp-e interval; and increased the QT dispersion and the Tp-e/QT ratio; decreased the VFT; and increased the serum concentrations of noradrenaline, C-reactive protein and interleukin-6. Renal denervation significantly attenuated these changes induced by CKD. The study demonstrated that RDN could decrease the susceptibility of the heart to ventricular fibrillation in this CKD model. Improvement of left ventricular hypertrophy, sympathetic activation and inflammation by RDN may be responsible for its beneficial effects.

ß1 -Adrenoceptor autoantibodies increase the susceptibility to ventricular arrhythmias involving abnormal repolarization in guinea-pigs.

NEW FINDINGS: What is the central question of this study? High titres of autoantibodies against the second extracellular loop of the ß1 -adrenergic receptor (ß1 -AAs) can be detected in the sera of patients with ventricular arrhythmias, but a causal relationship between ß1 -AAs and ventricular arrhythmias has not been established. What is the main finding and its importance? Monoclonal ß1 -AAs (ß1 -AR mAbs) were used in the experiments. We showed that ß1 -AR mAbs increased susceptibility to ventricular arrhythmias and induced repolarization abnormalities. Antibody adsorption of ß1 -AAs will be a potential new therapeutic strategy for ventricular arrhythmias in patients with high titres of ß1 -AAs. High titres of autoantibodies against the second extracellular loop of the ß1 -adrenergic receptor (ß1 -AAs) can be detected in sera from patients with ventricular arrhythmias, but a causal relationship between ß1 -AAs and ventricular arrhythmias has not been established. In this work, ECGs of guinea-pigs and isolated guinea-pig hearts were recorded. Ventricular tachycardia (VT) and ventricular fibrillation (VF) were evoked by programmed electrical stimulation of the left ventricular epicardium of isolated guinea-pig hearts. The monophasic action potential and effective refractory period of the left ventricle were recorded in paced isolated guinea-pig hearts. Furthermore, to increase the specificity, monoclonal autoantibodies against the second extracellular loop of the ß1 -adrenergic receptor (ß1 -AR mAbs) were used in all experiments. The results showed that ß1 -AR mAbs induced premature ventricular contractions in guinea-pigs and isolated guinea-pig hearts. In addition, ß1 -AR mAbs decreased the threshold of VT/VF and prolonged the duration of VT/VF. Furthermore, ß1 -AR mAbs shortened the corrected QT interval and effective refractory period, and prolonged late-phase repolarization of the monophasic action potential (MAPD90-30 ). These changes in electrophysiological parameters might be attributed, at least in part, to the arrhythmogenicity of ß1 -AR mAbs.

The impact of serum potassium-influencing antihypertensive drugs on the risk of out-of-hospital cardiac arrest: A case-control study.

AIMS: Sudden cardiac arrest (SCA) is a complex multifactorial event and most commonly caused by ventricular tachycardia/ fibrillation (VT/ VF). Some antihypertensive drugs could induce hypokalaemia or hyperkalaemia, which may increase susceptibility to VT/VF and SCA. OBJECTIVE: To assess the association between different classes of antihypertensive drugs classified according to their potential impact on serum potassium levels and the occurrence of out-of-hospital cardiac arrest (OHCA) based on VT/VF. METHODS: A case-control study was performed among current users of antihypertensive drugs. Cases were OHCA victims with electrocardiogram documented VT/VF drawn from the AmsteRdam REsuscitation STudies (ARREST) registry, and controls were non-OHCA individuals from the PHARMO database. Antihypertensive drugs were classified into: (i) antihypertensives with neutral effect on serum potassium levels; (ii) hypokalaemia-inducing antihypertensives; (iii) hyperkalaemia-inducing antihypertensives; (iv) combination of antihypertensives with hypo- and hyperkalaemic effects. RESULTS: We included 1345 cases and 4145 controls. The risk of OHCA was significantly increased among users of hypokalaemia-inducing antihypertensives [adjusted odds ratio (OR) 1.39; 95% confidence interval (CI) 1.10-1.76] and among users of a combination of antihypertensives with hypo- and hyperkalaemic effects (adjusted OR 1.42; 95%CI 1.17-1.72) vs. users of antihypertensives with neutral effect. There was no difference in OHCA risk between users of hyperkalaemia-inducing antihypertensives vs. users of antihypertensive drugs with neutral effect (adjusted OR 1.15; 95%CI 0.95-1.40). CONCLUSION: The risk of OHCA is significantly increased in patients who were current users of hypokalaemia-inducing antihypertensives and patients using a combination of antihypertensives with hypo- and hyperkalaemic effects.

Cerebral Hemodynamics and Metabolism During Cardiac Arrest and Cardiopulmonary Resuscitation Using Hyperspectral Near Infrared Spectroscopy.

BACKGROUND: Maintaining cerebral oxygen delivery and metabolism during cardiac arrest (CA) through resuscitation is essential to improve the survival rate while avoiding brain injury. The effect of CA and cardiopulmonary resuscitation (CPR) on cerebral and muscle oxygen delivery and metabolism is not clearly quantified.Methods and Results:A novel hyperspectral near-infrared spectroscopy (hNIRS) technique was developed and evaluated to measure cerebral oxygen delivery and aerobic metabolism during ventricular fibrillation (VF) CA and CPR in 14 pigs. The hNIRS parameters were measured simultaneously on the dura and skull to investigate the validity of non-invasive hNIRS measurements. In addition, we compared the hNIRS data collected simultaneously on the brain and muscle. Following VF induction, oxygenated hemoglobin (HbO2) declined with a 9.9 s delay and then cytochrome-c-oxidase (Cyt-ox) decreased on average 4.4 s later (P<0.05). CPR improved cerebral metabolism, which was reflected by an average 0.4 µmol/L increase in Cyt-ox, but had no significant effect on HbO2, deoxygenated hemoglobin (HHb) and tissue oxygen saturation (tSO2). Cyt-ox had greater correlation with HHb than HbO2. Muscle metabolism during VF and CPR was significantly different from that of the brain. The total hemoglobin concentration (in the brain only) increased after ~200 s of untreated CA, which is most likely driven by cerebral autoregulation through vasodilation. CONCLUSIONS: Overall, hNIRS showed consistent measurements of hemodynamics and metabolism during CA and CPR.

Galectin-3 correlates with arrhythmogenic right ventricular cardiomyopathy and predicts the risk of ventricular -arrhythmias in patients with implantable defibrillators.

Background Arrhythmogenic right ventricular dysplasia (ARVD) is a heritable disorder characterized by fibro-fatty replacement of right ventricular myocytes, increased risk of ventricular arrhythmias, and sudden cardiac death. Galectin-3 (GAL3) is known to play an important role in a number of fibrotic conditions, including cardiac fibrosis. Many studies have focused on the association between GAL3 levels and cardiac fibrosis in heart failure. However, the role of GAL3 in the pathogenesis of ARVD and ventricular arrhythmias has not yet been evaluated thoroughly. The aim of this study was to explore GAL3 levels in patients with ARVD and its association with ventricular arrhythmias. Methods Twenty-nine patients with ARVD and 24 controls were included. All patients with ARVD had an implantable cardiac defibrillator (ICD) for primary or secondary prevention. Ventricular arrhythmia history was obtained from a chart review and ICD data interrogation. Galectin-3 levels were measured using an enzyme-linked immunosorbent assay. Results Patients with ARVD had higher plasma GAL3 levels (16.9 ± 2.6 ng/mL vs 11.3 ± 1.8 ng/mL, P < 0.001) than the control group. Ten patients had sustained or non-sustained ventricular arrhythmias during follow-up. In the multivariable analysis, left ventricular disease involvement (HR: 1.05; 95% CI: [1.01-1.12]; P = 0.03); functional capacity >2 (HR: 1.21; 95% CI: [1.13-1.31]; P < 0.005); and GAL3 levels (HR: 1.05; 95% CI: [1.00-1.11]; P = 0.01) independently predicted VT/VF. Conclusion We demonstrated that serum GAL3 was significantly elevated in patients with ARVD. Also, serum GAL 3 levels could be regarded as a candidate biomarker in the diagnosis of ARVD which needs to be tested in larger prospective studies. In addition, GAL3 levels were higher in patients with VT/VF as compared with those without VT/VF.

Does therapeutic hypothermia during extracorporeal cardiopulmonary resuscitation preserve cardiac function?

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (E-CPR) is increasingly used as a rescue method in the management of cardiac arrest and provides the opportunity to rapidly induce therapeutic hypothermia. The survival after a cardiac arrest is related to post-arrest cardiac function, and the application of therapeutic hypothermia post-arrest is hypothesized to improve cardiac outcome. The present animal study compares normothermic and hypothermic E-CPR considering resuscitation success, post-arrest left ventricular function and magnitude of myocardial injury. METHODS: After a 15-min untreated ventricular fibrillation, the pigs (n = 20) were randomized to either normothermic (38 °C) or hypothermic (32-33 °C) E-CPR. Defibrillation terminated ventricular fibrillation after 5 min of E-CPR, and extracorporeal support continued for 2 h, followed by warming, weaning and a stabilization period. Magnetic resonance imaging and left ventricle pressure measurements were used to assess left ventricular function pre-arrest and 5 h post-arrest. Myocardial injury was estimated by serum concentrations of cardiac TroponinT and Aspartate transaminase (ASAT). RESULTS: E-CPR resuscitated all animals and the hypothermic strategy induced therapeutic hypothermia within minutes without impairment of the resuscitation success rate. All animals suffered a severe global systolic left ventricular dysfunction post-arrest with 50-70% reductions in stroke volume, ejection fraction, wall thickening, strain and mitral annular plane systolic excursion. Serum concentrations of cardiac TroponinT and ASAT increased considerably post-arrest. No significant differences were found between the two groups. CONCLUSIONS: Two-hour therapeutic hypothermia during E-CPR offers an equal resuscitation success rate, but does not preserve the post-arrest cardiac function nor reduce the magnitude of myocardial injury, compared to normothermic E-CPR. Trial registration FOTS 4611/13 registered 25 October 2012.

Inflammation markers are associated with metabolic syndrome and ventricular arrhythmia in patients with coronary artery disease.

BACKGROUND: Inflammation plays a major role in the development and progression of atherosclerosis and coronary artery disease (CAD). Inflammation markers, including white blood cell (WBC) count, C-reactive protein (CRP) and interleukin-6 (IL-6), are widely used for cardiovascular risk prediction. The aim of the study was to establish factors associated with WBC, CRP and IL-6 in patients with CAD. Two functional polymorphisms in genes encoding enzymes participating in adenosine metabolism were analyzed (C34T AMPD1, G22A ADA). METHODS: Plasma concentrations of IL-6 were measured using high-sensitivity ELISA kits, and the nephelometric method was used for high-sensitivity CRP (hs-CRP) measurement in 167 CAD patients. RESULTS: Presence of metabolic syndrome (MS) and its components, presence of heart failure, severity of CAD symptoms, severe past ventricular arrhythmia (sustained ventricular tachycardia [sVT] or ventricular fibrillation [VF]), lower left ventricle ejection fraction, higher left ventricle mass index, higher end-diastolic volume and higher number of smoking pack-years were significantly associated with higher WBC, CRP and IL-6. Strong associations with arrhythmia were observed for IL-6 (median 3.90 vs 1.89 pg/mL, p<0.00001) and CRP concentration (6.32 vs 1.47 mg/L, p=0.00009), while MS was associated most strongly with IL-6. CRP and IL-6 were independent markers discriminating patients with sVT or VF. There were no associations between AMPD1 or ADA genotypes and inflammation markers. CONCLUSIONS: WBC, CRP and IL-6 are strongly associated with components of the metabolic syndrome. Their strong association with life-threatening ventricular arrhythmia emphasizes the proarrhythmic role of inflammation in the increased cardiovascular risk of CAD patients.

Inducibility of ventricular fibrillation during mild therapeutic hypothermia: electrophysiological study in a swine model.

INTRODUCTION: Mild therapeutic hypothermia (MTH) is being used after cardiac arrest for its expected improvement in neurological outcome. Safety of MTH concerning inducibility of malignant arrhythmias has not been satisfactorily demonstrated. This study compares inducibility of ventricular fibrillation (VF) before and after induction of MTH in a whole body swine model and evaluates possible interaction with changing potassium plasma levels. METHODS: The extracorporeal cooling was introduced in fully anesthetized swine (n = 6) to provide MTH. Inducibility of VF was studied by programmed ventricular stimulation three times in each animal under the following: during normothermia (NT), after reaching the core temperature of 32°C (HT) and after another 60 minutes of stable hypothermia (HT60). Inducibility of VF, effective refractory period of the ventricles (ERP), QTc interval and potassium plasma levels were measured. RESULTS: Starting at normothermia of 38.7 (IQR 38.2; 39.8)°C, HT was achieved within 54 (39; 59) minutes and the core temperature was further maintained constant. Overall, the inducibility of VF was 100% (18/18 attempts) at NT, 83% (15/18) after reaching HT (P = 0.23) and 39% (7/18) at HT60 (P = 0.0001) using the same protocol. Similarly, ERP prolonged from 140 (130; 150) ms at NT to 206 (190; 220) ms when reaching HT (P < 0.001) and remained 206 (193; 220) ms at HT60. QTc interval was inversely proportional to the core temperature and extended from 376 (362; 395) at NT to 570 (545; 599) ms at HT. Potassium plasma level changed spontaneously: decreased during cooling from 4.1 (3.9; 4.8) to 3.7 (3.4; 4.1) mmol/L at HT (P < 0.01), then began to increase and returned to baseline level at HT60 (4.6 (4.4; 5.0) mmol/L, P = NS). CONCLUSIONS: According to our swine model, MTH does not increase the risk of VF induction by ventricular pacing in healthy hearts. Moreover, when combined with normokalemia, MTH exerts an antiarrhythmic effect despite prolonged QTc interval.

Influence of acute glycaemic level on measures of myocardial infarction in non-diabetic pigs.

OBJECTIVE: Patients with diabetes are at increased risk of experiencing myocardial infarction. The influence of the prevailing plasma glucose level on infarction and mortality after acute ischaemia is however unknown. The aim was to study the effect of the acute plasma glucose level on the myocardial infarction size in a closed-chest pig model. DESIGN: 38 non-diabetic pigs were randomised to hypoglycaemic (1.8-2.2 mmol/l; n = 15), normoglycaemic (5-7 mmol/l; n = 12) or hyperglycaemic glucose clamping (22-23 mmol/l; n = 11). After 30 min within glucose target myocardial infarction was induced for 30 min followed by reperfusion for 120 min. Hereafter the heart was double-stained to delineate infarction from viable tissue within the area at risk. RESULTS: Mean infarction size was 201 ± 35 mm(2) (mean ± SEM) in the hypoglycaemic group, 154 ± 40 mm(2) in the normoglycaemic group and 134 ± 40 mm(2) in the hyperglycaemic group, with no differences in infarction size, infarct/area at risk ratio or troponin T levels between the groups. There was no difference in incidence of ventricular fibrillation or mortality between the groups. CONCLUSION: No statistically significant associations were observed between the acute glycaemic level and measures of myocardial infarction, rates of ventricular fibrillation and subsequent premature death in the setting of acute ischaemia and reperfusion.

Osteopontin and galectin-3 predict the risk of ventricular tachycardia and fibrillation in heart failure patients with implantable defibrillators.

BACKGROUND: Myocardial extracellular matrix remodelling provides electrical heterogeneity entailing ventricular tachycardia/fibrillation (VT/VF) in heart failure (HF) patients. Osteopontin (OPN) and Galectin-3 (Gal-3) are fibrosis markers and may reflect the extension of the arrhythmogenic substrate. We assessed whether plasma OPN and Gal-3 predict the risk of sustained VT/VF in a cohort of HF patients with implantable cardioverter-defibrillator (ICD). METHODS: A total of 75 HF patients underwent pre-ICD implantation clinical evaluation and assessment of plasma OPN and Gal-3. The primary endpoint was the time to the occurrence of the first sustained VT/VF. Hazard ratios (HR) were derived from Cox proportional-hazards analysis. RESULTS: Patients with coronary artery disease (CAD) had higher plasma OPN (79.8 ± 44.0 ng/mL vs. 66.0 ± 31.8 ng/mL; P = 0.04). Both Gal-3 (r = -0.38; P = 0.01) and OPN (r = -0.27; p = 0.01) were negatively related to estimated glomerular filtration rate. After 29 ± 17 months, 20 patients (27%) reached the primary endpoint. Patients with VT/VF had higher plasma OPN and Gal-3 (97.4 ± 51.7 ng/mL vs. 65.9 ± 31.3 ng/mL; P = 0.002 and 19.7 ± 8.5 ng/mL vs. 16.2 ± 6.2 ng/mL; P = 0.05). In univariate analysis, OPN (log-OPN, HR: 32.4; 95%CI: 3.9-264.7; P = 0.001) and Gal-3 (HR: 1.05; 95%CI: 1.00-1.11; P = 0.04) predicted sustained VT/VF. In multivariable analysis, both OPN (HR: 41.4; 95%CI: 3.8-441.9; P = 0.002) and Gal-3 (HR: 1.06; 95%CI: 1.00-1.12; P = 0.03) retained their prognostic power after correction for age, sex, history of MI, EF, NYHA class, eGFR, use of ACE-I, and amiodarone. CONCLUSIONS: Plasma OPN and Gal-3 predict sustained VT/VF in HF patients at high risk for SCD. Larger prospective studies should outline the role of these biomarkers in predicting SCD on top of conventional risk stratification.

Status 2 patients had poor prognosis without mechanical circulatory support.

BACKGROUND: Indication for mechanical circulatory support (MCS) has been a matter of debate in less sick status 2 patients. METHODS AND RESULTS: Data were obtained from 183 consecutive patients assigned to stage D heart failure (HF) who were evaluated by the institutional review board of the University of Tokyo Hospital and then listed for heart transplantation as status 1 or 2 of the Japan Organ Transplant Network. Patients with status 2 (n=38) had a prognosis as poor as those dependent on inotropes (n=54) or MCS (n=91; P=0.615, log-rank test), and only 4 of them had eventual ventricular assist device (VAD) implantation (10.5%). Patients who eventually received VAD (n=92) had better 4-year survival than those without MCS among status 1 and 2 (P=0.030, log-rank test). On Cox regression analysis plasma B-type natriuretic peptide (BNP) >740pg/ml was the only significant predictor for 4-year survival among the status 2 group (P=0.014; hazard ratio, 8.267). Ten patients with status 2 died: 6 due to acute hemodynamic compromise and 4 due to ventricular fibrillation. CONCLUSIONS: Prognosis in status 2 patients was as poor as that of those dependent on inotrope infusion or VAD, mostly because of out-of-hospital sudden death without MCS. Status 2 patients with considerably high plasma BNP may be good candidates for continuous flow VAD therapy.

Severe hypokalemia probably associated with sertraline use.

OBJECTIVE: To report a case of ventricular fibrillation caused by severe hypokalemia probably associated with sertraline use. CASE SUMMARY: A 48-year-old male patient experienced ventricular fibrillation and cardiac arrest 2 hours after an uneventful coronary angiography procedure, which revealed normal, unobstructed coronary arteries. Blood chemistry was immediately obtained, revealing a very low potassium (K+) level of 2.44 mEq/L. Other blood electrolytes, including magnesium, ECG, and corrected QT intervals, were all within normal limits. A thorough search for an etiology of hypokalemia, including adrenal gland causes, herbal product consumption, and toxic exposure, did not reveal any identifiable cause. This led us to consider the only drug he was on--sertraline 50 mg per day--as the possible culprit. DISCUSSION: There has been no clear identification of severe hypokalemia associated with sertraline use in the literature. However, there have been a considerable number of self-reported cases of hypokalemia in patients on sertraline therapy. Scoring according to the Naranjo adverse drug reaction scale revealed a probable relationship between severe hypokalemia and sertraline use in our patient. No clear pathogenic mechanism for the effect of sertraline on serum K equilibrium is known. However, considering the number of self-reported incidences and this case report, the effect of sertraline on serum K levels warrants consideration. CONCLUSIONS: This is the first documented case report of severe hypokalemia probably associated with sertraline use.

Prognostic value of high-sensitivity troponin T levels in patients with ventricular arrhythmias and out-of-hospital cardiac arrest: data from the prospective FINNRESUSCI study.

INTRODUCTION: Myocardial dysfunction is common after out-of-hospital cardiac arrest (OHCA) and high-sensitivity troponin T (hs-TnT) levels may provide incremental prognostic information to established risk indices. METHODS: A total of 155 patients with OHCA and a shockable rhythm (98% ventricular fibrillation; OHCA-VF/VT) had blood samples drawn within six hours of admission. Blood samples were also available after 24 hours, 48 hours, and 96 hours in subsets of patients. The endpoints of the study were hospital mortality and neurological status and mortality after one year. RESULTS: Admission hs-TnT levels were higher than the 99-percentile of the general population (14 ng/L) in all patients (range 18 to 17,837 ng/L). Admission hs-TnT levels were associated with acute coronary artery occlusion, time to return of spontaneous circulation, heart failure, and renal function. Admission hs-TnT levels were higher in one-year non-survivors compared to survivors (median 747 (quartile 1 to 3, 206 to 1061) ng/L versus 345 (184 to 740) ng/L, P =0.023) and in patients with a poor versus a favorable neurological outcome (739 (191 to 1061) ng/L versus 334 (195 to 716) ng/L, P =0.028). However, hs-TnT measurements did not add prognostic information to established risk variables in multivariate analyses. hs-TnT levels measured during the hospitalization for OHCA-VF/VT correlated closely with admission levels (r ≥0.63) and were inferior to Simplified Acute Physiology Score II (SAPS II) scores for the prediction of events during follow-up. hs-TnT dynamics did not discriminate between survivors and non-survivors or between a poor versus a favorable neurological outcome. CONCLUSION: hs-TnT levels are elevated in critically ill patients with OHCA-VF/VT, but do not improve risk prediction.

Altered platelet contents in survivors of early ischemic ventricular fibrillation: preliminary findings.

Early ischemic ventricular fibrillation (VF) in the setting of an acute myocardial infarction (AMI) due to thrombotic coronary occlusion remains a major health problem. Several animal studies have shown that platelet-dense granule contents released during thrombus formation can induce arrhythmias. We hypothesize that the platelet release reaction is involved in the predisposition to early ischemic VF. A case-control study was performed in patients who survived VF during a first AMI ("cases," n = 26) and in patients with one previous AMI without arrhythmias ("controls," n = 24). All patients were on aspirin 100 mg OD. Baseline platelet activation was assessed with flow cytometry. Response to activation was assessed with aggregometry, flow cytometry and PFA-100 analysis. Differences in platelet contents and content release were assessed by labeling platelet-dense granules with mepacrine and by measuring serotonin and ADP/ATP content. Patient and infarct characteristics and baseline platelet function tests were similar between groups. The mean time from event was 4.9 (±3.2) years among cases and 4.7 (±2.7) years among controls. Dense granule release was similar in cases versus controls. Platelet serotonin content in cases was higher than in controls (611 ± 118 ng/10E(9) platelets vs. 536 ± 141 ng/10(9), p = 0.048). Even years after the event, elevations in the platelet dense granule contents between VF survivors and controls may be detected. These preliminary findings shed new light on the pathophysiological mechanisms underlying ischemic VF, as platelet-dense granules may contain mediators of early ischemic VF risk.

Evaluation of long-term pituitary functions in patients with severe ventricular arrhythmia: a pilot study.

INTRODUCTION: Traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), stroke and cerebrovascular disease (CVD) are identified as risk factors for hypopituitarism. Pituitary dysfunction after TBI, SAH, and CVD may present in the acute phase or later in the course of the event. Chronic hypopituitarism, particularly growth hormone (GH) deficiency is related to the increased cardiovascular morbidity and mortality. In patients with serious ventricular arrhythmias, who need cardiopulmonary resuscitation, brain tissue is exposed to short-term severe ischemia and hypoxia. However, there are no data in the literature regarding pituitary dysfunction after ventricular arrhythmias. PATIENTS AND METHODS: Forty-four patients with ventricular arrhythmias [ventricular tachycardia (VT), ventricular fibrillation (VF)] (mean age, 55.6 ± 1.8 years; 37 men, 7 women) were included in the study. The patients were evaluated after mean period of 21.2 ± 0.8 months from VT-VF. Basal hormone levels, including serum free triiodothyronine (fT3), free thyroxine (fT4), TSH, ACTH, prolactin, FSH, LH, total testosterone, estradiol, IGF-1, and cortisol levels were measured in all patients. To assess (GH)-insulin like growth factor-1 (IGF-1) axis, glucagon stimulation test was performed and 1 µg ACTH stimulation test was used for assessing hypothalamic-pituitary-adrenal (HPA) axis. RESULTS: The frequencies of GH, gonadotropin and TSH deficiency were 27.2, 9.0, 2.2%, respectively. Mean IGF-1 levels were lower in GH deficiency group, but it was not statistically significant. CONCLUSION: The present preliminary study showed that ventricular arrhythmias may result in hypopituitarism, particularly in growth hormone deficiency. Unrecognized hypopituitarism may be responsible for some of the cardiovascular problems at least in some patients.

Low serum eicosapentaenoic acid level is a risk for ventricular arrhythmia in patients with acute myocardial infarction: a possible link to J-waves.

Eicosapentaenoic acid (EPA) has antiarrhythmic effects. The J-wave on an electrocardiogram is associated with a high incidence of ventricular tachycardia/fibrillation (VT/VF). We evaluated relationships between EPA and J-waves, and their involvement in the occurrence of VT/VF in acute myocardial infarction (AMI). Two hundred consecutive patients undergoing successful percutaneous coronary intervention within 12 h after AMI onset were enrolled. Serum EPA level and J-waves at admission were evaluated. The patients were divided into two groups according to the optimal cutoff value (2.94) of serum EPA level (% of total fatty acids): LOW (<2.94, 61 ± 11 years, n = 103) and HIGH groups (≥2.94, 70 ± 13 years, n = 81). J-waves were observed more frequently in the LOW (36/103, 35 %) than in HIGH group (16/81, 20 %) (P = 0.020). The 30-day incidence of VT/VF including those occurring before admission was higher in the LOW (19.5 %) than in HIGH group (6.2 %) (P = 0.009). The patients with J-waves showed a higher incidence of VT/VF (23.1 %) than those without J-waves (9.9 %) (P = 0.019). Kaplan-Meier analysis showed that the highest incidence of VT/VF was observed in the LOW with J-wave group (27.8 %), followed by the LOW without J-wave (15.0 %), HIGH with J-wave (12.5 %), and HIGH without J-wave (4.6 %) (P = 0.013). Cox proportional hazard analysis revealed that Killip grade and low serum EPA level or presence of J-waves were significantly associated with the incidence of VT/VF. Low serum EPA level is a risk for incidence of VT/VF in the acute phase of myocardial infarction. Involvement of the J-wave and its possible link with EPA in the pathogenesis of ischemia-induced VT/VF are suggested.