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.

IL-18 mediates sickle cell cardiomyopathy and ventricular arrhythmias.

Previous reports indicate that IL18 is a novel candidate gene for diastolic dysfunction in sickle cell disease (SCD)-related cardiomyopathy. We hypothesize that interleukin-18 (IL-18) mediates the development of cardiomyopathy and ventricular tachycardia (VT) in SCD. Compared with control mice, a humanized mouse model of SCD exhibited increased cardiac fibrosis, prolonged duration of action potential, higher VT inducibility in vivo, higher cardiac NF-κB phosphorylation, and higher circulating IL-18 levels, as well as reduced voltage-gated potassium channel expression, which translates to reduced transient outward potassium current (Ito) in isolated cardiomyocytes. Administering IL-18 to isolated mouse hearts resulted in VT originating from the right ventricle and further reduced Ito in SCD mouse cardiomyocytes. Sustained IL-18 inhibition via IL-18-binding protein resulted in decreased cardiac fibrosis and NF-κB phosphorylation, improved diastolic function, normalized electrical remodeling, and attenuated IL-18-mediated VT in SCD mice. Patients with SCD and either myocardial fibrosis or increased QTc displayed greater IL18 gene expression in peripheral blood mononuclear cells (PBMCs), and QTc was strongly correlated with plasma IL-18 levels. PBMC-derived IL18 gene expression was increased in patients who did not survive compared with those who did. IL-18 is a mediator of sickle cell cardiomyopathy and VT in mice and a novel therapeutic target in patients at risk for sudden death.

Enhanced monocyte migratory activity in the pathogenesis of structural remodeling in atrial fibrillation.

BACKGROUND AND AIMS: Pathophysiological roles of monocytes in atrial fibrillation (AF), particularly for the progression of structural remodeling of the left atrium (LA), remain elusive. This study examined the association between the characteristics of circulating and local monocytes and extent of structural remodeling in LA, gauged by LA size, in AF patients. METHODS: First, 161 AF patients who were referred for catheter ablation were enrolled and divided into two groups according to the median of LA diameter (≤39 mm: normal LA group, >39 mm: enlarged LA group). As a control group, 22 patients underwent catheter ablation for paroxysmal supraventricular tachycardia (PSVT) without history of AF were analyzed. Blood samples were collected for flow cytometric analyses to evaluate monocyte subsets based on the levels of CD14 and CD16. Moreover, monocytes were isolated from blood to measure CC chemokine receptor 2 (CCR2) transcripts and protein levels, and migratory activity toward monocyte chemoattractant protein 1 (MCP-1). Second, to characterize the local monocytes in the atrial wall in AF, the resected left atrial appendages (LAA) in AF patients underwent cardiac surgery were histologically evaluated (n = 20). RESULTS: The proportions of monocyte subsets based on CD14 and CD16 expressions were not significantly different between the normal and enlarged LA group. Both transcripts and total protein levels of CCR2 in monocytes were higher in the enlarged LA group compared to those in the normal LA group. In the enlarged LA group, monocytes exhibited more enhanced migratory activity than the normal LA group. Moreover, we found a significantly higher number of CCR2-positive monocytes/macrophages in the LAA in the enlarged LA group. CONCLUSION: Enhanced migratory activity in circulating and local monocytes may play a pivotal role in the pathogenesis of progression in atrial remodeling in AF patients.

Correlations between cardiac troponin I and nonsustained ventricular tachycardia in hypertrophic obstructive cardiomyopathy.

BACKGROUND: Nonsustained ventricular tachycardia (NSVT) is an independent risk factor for sudden cardiac death (SCD) in patients with hypertrophic obstructive cardiomyopathy (HOCM). However, data concerning the correlations of cardiac biomarkers and NSVT in HOCM are rather limited. HYPOTHESIS: Our study aimed to investigate the associations between the occurrence of NSVT and circulating biomarkers representing myocardial injury (cardiac troponin I, cTnI), cardiac function (N-terminal pro-brain natriuretic peptide, NT-pro BNP), and inflammation (high-sensitivity C-reactive protein) in a large Chinese HOCM cohort. METHODS: A total of 755 consecutive HOCM patients were recruited. Systematic cardiac evaluations and circulating biomarkers were examined routinely in all subjects under the clinically stable status. According to the results of 24-hour Holter monitoring, patients were divided into the NSVT group (n = 138) and the nonventricular tachycardia (non-VT) group (n = 617). RESULTS: Compared with the non-VT group, circulating levels of both cTnI and NT-pro BNP elevated significantly in patients with positive NSVT episodes (P < .001). Multivariable analyses demonstrated that cTnI was independently associated with the presence of NSVT (OR = 1.675, 95% CI: 1.406-1.994, P < .001). Concentrations of cTnI increased progressively not only with the aggravation of ventricular arrhythmic events (P < .001), but also with the growing risk of SCD in HOCM patients (P < .001). Serum cTnI ≥ 0.0265 ng/mL indicated predictive value for the occurrence of NSVT in the HOCM cohort (area under the curve = 0.707, 95% CI: 0.660-0.754, P < .001). CONCLUSIONS: Elevated cTnI was an independent determinant of NSVT, and it seemed to be valuable for assessing the clinical status of ventricular arrhythmias and the risk of SCD in patients with HOCM.

Electrolyte Abnormalities in Patients Presenting With Ventricular Arrhythmia (from the LYTE-VT Study).

Electrolyte abnormalities are a known trigger for ventricular arrhythmia, and patients with heart disease on diuretic therapy may be at higher risk for electrolyte depletion. Our aim was to determine the prevalence of electrolyte depletion in patients presenting to the hospital with sustained ventricular tachycardia or ventricular fibrillation (VT/VF) versus heart failure, and identify risk factors for electrolyte depletion. Consecutive admissions to a tertiary care hospital for VT/VF were identified between July 2016 and October 2018 using the electronic medical record and compared with an equal number of consecutive admissions for heart failure (CHF). The study included 280 patients (140 patients in each group; mean age 63, 60% male, 59% African American). Average EF in the VT/VF and CHF groups was 30% and 33%, respectively. Hypokalemia (K < 3.5 mmol/L) and severe hypokalemia (K < 3.0 mmol/L) were present in 35.7% and 13.6%, respectively, of patients with VT/VF, compared to 12.9% and 2.7% of patients with CHF (p < 0.001 and p = 0.001, respectively, between groups). Hypomagnesemia was found in 7.8% and 5.8% of VT/VF and CHF patients, respectively (p = 0.46). Gastrointestinal illness and recent increases in diuretic dose were strongly associated with severe hypokalemia in VT/VF patients (odds ratio: 11.1 and 21.9, respectively; p < 0.001). In conclusion, hypokalemia is extremely common in patients presenting with VT/VF, much more so than in patients with CHF alone. Preceding gastrointestinal illness and increase in diuretic dose were strongly associated with severe hypokalemia in the VT/VF population, revealing a potential opportunity for early intervention and arrhythmia risk reduction.

Prognostic impact of potassium levels in patients with ventricular tachyarrhythmias.

BACKGROUND: The study sought to assess the prognostic impact of potassium levels (K) in patients with ventricular tachyarrhythmias. METHODS: A large retrospective registry was used including all consecutive patients presenting with ventricular tachyarrhythmias on admission from 2002 to 2016. Patients with hypokalemia (i.e., K < 3.3 mmol/L), normokalemia (i.e., K 3.3-4.5 mmol/L), and hyperkalemia (i.e., K > 4.5 mmol/L) were compared applying multi-variable Cox regression models and propensity-score matching for evaluation of the primary endpoint of all-cause mortality at 3 years. Secondary endpoints were early cardiac death at 24 h, in-hospital death, death at 30 days, as well as the composite endpoint of early cardiac death at 24 h, recurrences of ventricular tachyarrhythmias, and appropriate ICD therapies at 3 years. RESULTS: In 1990 consecutive patients with ventricular tachyarrhythmias, 63% of the patients presented with normokalemia, 30% with hyperkalemia, and 7% with hypokalemia. After propensity matching, both hypokalemic (HR = 1.545; 95% CI 0.970-2.459; p = 0.067) and hyperkalemic patients (HR = 1.371; 95% CI 1.094-1.718; p = 0.006) were associated with the primary endpoint of all-cause mortality at 3 years compared to normokalemic patients. Hyperkalemia was associated with even worse prognosis directly compared to hypokalemia (HR = 1.496; 95% CI 1.002-2.233; p = 0.049). In contrast, potassium measurements were not associated with the composite endpoint at 3 years. CONCLUSION: In patients presenting with ventricular tachyarrhythmias, normokalemia was associated with best short- and long-term survival, whereas hyperkalemia and hypokalemia were associated with increased mortality at 30 days and at 3 years.

Cardiac troponin I is associated with non-sustained ventricular tachycardia in patients with hypertrophic obstructive cardiomyopathy.

As highly sensitive and specific markers of myocardial damage, cardiac troponins were demonstrated to correlate with clinical parameters of patients with hypertrophic cardiomyopathy. However, the relationship between cardiac troponins and presence of non-sustained ventricular tachycardia (NSVT) in hypertrophic cardiomyopathy remains unclear. The aim of our study was to explore the association between serum cardiac troponin I (cTNI) and presence of NSVT in patients with hypertrophic obstructive cardiomyopathy (HOCM). A total of 309 HOCM patients were enrolled in our study. All participants underwent clinical evaluations, including collections of medical history, blood tests, 24-h Holter monitoring, echocardiography, and cardiac magnetic resonance imaging. There were 53 (17.2%) patients with NSVT and 256 patients without it. Compared to patients without NSVT, serum cTNI (P < 0.001) and plasma NT-proBNP (P = 0.042) were significantly higher in patients with NSVT. Moreover, cTNI and NT-proBNP were positively correlated with left atrial diameter, maximum wall thickness (MWT), left ventricular volume index and left ventricular mass index. In multivariable logistic analysis, log cTNI [odds ratio (OR) = 2.408, 95% confidence interval (CI) 1.108-5.325, P = 0.027], left ventricular end-diastole diameter (OR = 0.922, 95%CI 0.856-0.994, P = 0.034), MWT (OR = 1.131, 95%CI 1.035-1.235, P = 0.006) and left ventricular end-systole volume index (OR = 1.060, 95%CI 1.025-1.096, P = 0.001) were independent determinants of NSVT occurrence after adjustment for potential cofounders. Serum cTNI level was elevated in patients with NSVT. And it was independently associated with NSVT in patients with HOCM. Our results suggest that it may be more reasonable for HOCM patients with elevated serum cTNI to extend the time of Holter monitoring.

Big endothelin-1 as a clinical marker for ventricular tachyarrhythmias in patients with post-infarction left ventricular aneurysm.

OBJECTIVE: Ventricular tachyarrhythmia is the leading cause of death in post-infarction patients. Big endothelin-1 (ET-1) is a potent vasoconstrictor peptide and plays a role in ventricular tachyarrhythmia development. The aim of this study was to investigate the association between the serum concentration of big ET-1 and ventricular tachyarrhythmia in post-infarction left ventricular aneurysm (PI-LVA) patients. METHODS: A total of 222 consecutive PI-LVA patients who had received medical therapy were enrolled in the study. There were 43 (19%) patients who had ventricular tachycardia/ventricular fibrillation (VT/VF) at the time of admission. The clinical characteristics were observed and the plasma big ET-1 level was measured. Associations between big ET-1 and the presence of VT/VF were assessed. Patients were followed up to check for outcomes related to cardiovascular mortality, VT/VF attack, and all-cause mortality. RESULTS: The median concentration of big ET-1 was 0.635 pg/mL. Patients with big ET-1 concentrations above the median were more likely to have higher risk clinical features. There was a positive correlation between the level of big ET-1 with VT/VF attack (r=0.354, p<0.001). In the multiple logistic regression analysis, big ET-1 (OR=4.06, 95% CI: 1.77-9.28, p<0.001) appeared as an independent predictive factor for the presence of VT/VF. Multiple Cox regression analysis suggested that big ET-1 concentration was independently predictive of VT/VF attack (OR=2.5, 95% CI 1.4-4.5, p<0.001). NT-proBNP and left ventricular ejection fraction of ≤35% were demonstrated to be independently predictive of cardiovascular mortality and all-cause mortality. CONCLUSION: Increased big ET-1 concentration in PI-LVA patients is a valuable independent predictor for the prevalence of ventricular tachyarrhythmias and VT/VF attacks during follow-up after PI-LVA treatment.

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.

Differential Diagnosis Between Catecholaminergic Polymorphic Ventricular Tachycardia and Long QT Syndrome Type 1　- Modified Schwartz Score.

BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) has been often misdiagnosed as long QT syndrome (LQTS) type 1 (LQT1), which phenotypically mimics CPVT but has a relatively better prognosis. Methods and Results: The derivation and validation cohorts consisted of 146 and 21 patients, respectively, all of whom had exercise- or emotional stress-induced cardiac events. In the derivation cohort, 42 and 104 patients were first clinically diagnosed with CPVT and LQTS, respectively. Nine of 104 patient who had initial diagnosis of LQTS were found to carry RYR2 mutations. They were misdiagnosed due to 4 different reasons: (1) transient QT prolongation after cardiopulmonary arrest; (2) QT prolongation after epinephrine test; (3) absence of ventricular arrhythmia after the exercise stress test (EST); and (4) assumption of LQTS without evidence. Based on genetic results, we constructed a composite scoring system by modifying the Schwartz score: replacing the corrected QT interval (QTc) at 4 min recovery time after EST >480 ms with that at 2 min, or with ∆QTc (QTc at 2 min of recovery-QTc before exercise) >40 ms and assigning a score of -1 for ∆QTc <10 ms or documented polymorphic ventricular arrhythmias. This composite scoring yielded 100% sensitivity and specificity for the clinical differential diagnosis between LQT1 and CPVT when applied to the validation cohort. CONCLUSIONS: The modified Schwartz score facilitated the differential diagnosis between LQT1 and CPVT.

Chronic median nerve modulation reduces ventricular arrhythmia and improves ventricular function in a postmyocardial infarction rabbit model.

AIM: Median nerve stimulation (MNS) is a novel neuromodulation approach for treatment of ventricular arrhythmia, but little is known about its chronic effects. The aim of this study was to investigate the effects of chronic MNS on ventricular arrhythmia and ventricular dysfunction postmyocardial infarction (MI). METHOD: Two weeks after MI, 12 rabbits were randomly divided into control and MNS groups, and chronic MNS was performed in MNS group for 2 weeks. Ventricular function and arrhythmias; sympathetic innervation and activity; and interleukin-1 ß (IL-1 ß) and norepinephrine (NE) levels were analyzed. RESULTS: Both the total number of premature ventricular complex and episodes of ventricular tachycardia were lower in MNS group than in control group (20 560 ± 10 314 beats vs 70 079 ± 37 184 beats, P = .021, and 115 ± 63 episodes vs 307 ± 164 episodes, P = .034, respectively). Compared with control group, MNS decreased the cardiac sympathetic nerve density and level of circulating NE in MNS group (1798.42 ± 644.07 µm2 /mm2 vs 1003.79 ± 453.00 µm2 /mm2, P = .041, and 20.86 ± 4.54 pg/mL vs 11.07 ± 1.43 pg/mL, P = .002, respectively). MNS also improved the left ventricular ejection fraction (59.07 ± 1.91% vs 49.77 ± 3.47%, P = .003) and inhibited the level of IL-1 ß in serum (69.19 ± 4.71 pg/mL vs 85.93 ± 12.80 pg/mL, P = .013). CONCLUSION: Chronic MNS appears to protect against ventricular arrhythmia and improves ventricular function post-MI, which may be mediated by suppressing cardiac sympathetic activity and anti-inflammatory effects.

Association between Serum Uric Acid Level and Ventricular Tachyarrhythmia in Heart Failure Patients with Implantable Cardioverter-Defibrillator.

OBJECTIVES: The uric acid (UA) level is related to cardiac events and mortality, but little is known about the clinical significance of serum UA with regard to the ventricular tachyarrhythmia (VT) risk in patients with heart failure. METHODS: The present study enrolled 56 patients with ischemic and nonischemic cardiomyopathy (37 males, mean age 64.7 ± 11.1 years) who received prophylactic implantable cardioverter-defibrillator (ICD) implantation. Based on a median serum UA value, study subjects were divided into two groups: serum UA < 6.1 mg/dL (group L, n = 29) and ≥6.1 mg/dL (group H, n = 27). Echo- and electrocardiograms (QRS duration and QTc intervals) were examined in each group. RESULTS: During the follow-up period (30 ± 8 months), 22 (39%) patients had appropriate ICD therapies for sustained VT. There was no significant difference in the electro- and echocardiographic data between both groups. However, appropriate ICD therapies were significantly higher in group H than in group L (p = 0.02). In multivariate analysis, UA was an independent predictor of appropriate ICD therapies (hazard ratio 1.826, 95% confidence interval 1.248-2.671, p = 0.002). CONCLUSIONS: Serum UA levels might be a predictor of VT, providing new aspects regarding the decision to adapt ICD implantation in patients with heart failure.

Association of serum potassium concentration with mortality and ventricular arrhythmias in patients with acute myocardial infarction: A systematic review and meta-analysis.

Background Challenging clinical practice guidelines that recommend serum potassium concentration between 4.0-5.0 mEq/L or ≥4.5 mEq/L in patients with acute myocardial infarction, recent studies found increased mortality risks in patients with a serum potassium concentration of ≥4.5 mEq/L. Studies investigating consequences of hypokalemia after acute myocardial infarction revealed conflicting results. Therefore, the aim of this systematic review and meta-analysis was to combine evidence from previous studies on the association of serum potassium concentration with both short and long-term mortality as well as the occurrence of ventricular arrhythmias. Design Systematic review and meta-analysis. Methods A structured search of MEDLINE and EMBASE databases yielded 23 articles published between 1990 and January 2017 that met the inclusion criteria. Study selection, data extraction and quality assessment were carried out by three reviewers. Random effects models were used to pool estimates across the included studies and sensitivity analyses were performed when possible. Results Twelve studies were included in the meta-analysis. Both pooled results from six studies investigating short-term mortality and from five studies examining long-term mortality revealed significantly increased risks in patients with serum potassium concentrations of <3.5 mEq/L, 4.5-<5.0 mEq/L and ≥5.0 mEq/L after acute myocardial infarction. In addition, a serum potassium concentration of <3.5 mEq/L was significantly associated with the occurrence of ventricular arrhythmias. Conclusions Mortality, both short and long term, and the occurrence of ventricular arrhythmias in patients with acute myocardial infarction seem to be negatively associated with hypokalemic serum potassium concentration. There is evidence for adverse consequences of serum potassium concentrations of ≥4.5 mEq/L. Due to the heterogeneity among existing studies, further research is necessary to confirm the need to change clinical practice guidelines.