Pan-immune-inflammation value predicts sustained ventricular arrhythmias in NSTEMI: a novel inflammatory risk marker

Objective: To explore the predictive ability of Tp-ec, Q-Tc, Tp-e/Q-T and HRV on malignant arrhythmia during hospitalization. Method: 100 patients with malignant ventricular arrhythmia were included as the experimental group, another 100 patients without malignant ventricular arrhythmia were included as control group. The differences of Tp-ec, Q-Tc, Tp-e/Q-T and HRV were compared between the two groups. Multivariate logistic regression analysis was used to study variables and establish prediction model. ROC curve was used to evaluate the predictive ability and best predictive value of each index for malignant ventricular arrhythmia in hospital. Result: Compared with the control group, Tp-ec, Q-Tc, Tp-e/Q-T and HRV in the experimental group were significantly increased, (P < 0.001), HRV was decreased significantly. Multivariate logistic regression showed that the increase of Tp-ec, Q-Tc, Tp-e/Q-T and the decrease of HRV were the risk factors of malignant ventricular ventricular arrhythmia in hospital (OR = 11.169, 1.788, 1.001, 0.780), and bulid prediction model Z = -254.827 + 0.203 * Tp-ec + 0.581 * Q-Tc + 878.066 * Tp-e/Q-T-0.248 * SDNN. ROC curve showed that the area under the curve (AUC) of TP EC, Q-Tc, Tp-e/Q-T, HRV and predictive model for the diagnosis of malignant ventricular ventricular arrhythmia in hospital were 0.988, 0.905, 0.973, 0.901, 0.993, the best critical values were 100.365 ms, 447.078 ms, 0.239, 100.500, 181.792. Conclusion: The decrease of Tp-ec, Q-Tc, Tp-e/Q-T and HRV were the risk factors of malignant ventricular arrhythmia, and has predictive value for malignant ventricular arrhythmia in hospital. The prediction model combined with Tp-ec, Q-Tc, Tp-e/Q-T and HRV can improve the prediction ability of variables on malignant ventricular arrhythmia in hospital.

Funding Acknowledgements None. Background Patients with acute coronary syndrome (ACS) have a high arrhythmic burden, and either ventricular and supraventricular arrhythmias are very common during hospitalization[1]. Patients who develop arrhythmias show higher mortality and worse prognosis. The PRAISE (Prediction of Adverse Events Following an Acute Coronary Syndrome) score is a machine-learning based model for predicting 1-year all cause death, recurrent acute myocardial infarction and major bleedings in patients after ACS[2]. To date, its role to predict arrhythmic complications in ACS remains unknown. Purpose We hypothesized that patients with higher PRAISE score have a higher arrhythmic burden. Aim was to evaluate in a prospective protocol the PRAISE score capability for identifying patients with ACS at higher risk of arrhythmic complications during in-hospital stay. Methods A total of 365 consecutive patients admitted to our cardiac intensive care unit for ACS and undergoing percutaneous coronary intervention were enrolled. All patient was monitored by continuous electrocardiogram during hospitalization. The PRAISE score was obtained for each patient &amp;lt;24 hours from admission. Patients were divided into 2 groups based on the results of the PRAISE score for all-cause of death as patients without high PRAISE score (e.g. with low to intermediate risk, n=350) and patients with high PRAISE score (e.g. with high risk, n=15). The occurrence of atrial fibrillation (AF) and ventricular arrhythmias (VAs) up to discharge was recorded. AF was defined by detection of at least one episode of uncoordinated atrial electrical activation and irregular R-R intervals, in absence of distinct repeating P waves and with irregular atrial activations lasting at least 5 minutes. We considered as VAs all episodes of ventricular non-sustained tachycardia, sustained ventricular tachycardia and ventricular fibrillation. Results ROC curve analysis indicated a significant relationship between high PRAISE score and risk of both in-hospital AF (AUC 0.89, 95%CI 0.82-0.94, p=0.0001) and VAs (AUC 0.69, 95%CI 0.64-0.75, p=0.0001). A high PRAISE score had a specificity of 99% for AF and 92% for VAs. By Kaplan-Meier analysis, patients with high PRAISE score more frequently developed AF (30% vs 4% in those without high score; log rank p=0.00001) and VAs (77% vs 35%; log rank p=0.00001). Multivariate analysis showed that a high PRAISE score was an independent predictor of both AF (HR 4.08, 95%CI 1.14-14.58, p=0.030) and VAs (HR 2.36, 95%CI 1.08-5.14, p=0.030). Conclusions In patients hospitalized for ACS, the PRAISE score has a comprehensive capability to identify with high specificity those patients prone to develop arrhythmic events during hospitalization. This may be important in order to stratify patients with higher arrhythmic risk in whom individualized strategies may improve the clinical outcome.Baseline features of the populationKaplan-Meier anaysis

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High-Resolution ECG for Predicting Ventricular Arrhythmia in Hypertrophic Cardiomyopathy: Another Tool in the Toolbox.

Tumor necrosis factor-α: a new mechanism of ischemic ventricular fibrillation?

BACKGROUND:Variants in RBM20 are reported in 2% to 6% of familial cases of dilated cardiomyopathy and may be associated with fatal ventricular arrhythmia and rapid heart failure progression. We sought to determine the risk of adverse events in RBM20 variant carriers and the impact of sex on outcomes.METHODS:Consecutive probands and relatives carrying RBM20 variants were retrospectively recruited from 12 cardiomyopathy units. The primary end point was a composite of malignant ventricular arrhythmia (MVA) and end-stage heart failure (ESHF). MVA and ESHF end points were also analyzed separately and men and women compared. Left ventricular ejection fraction (LVEF) contemporary to MVA was examined. RBM20 variant carriers with left ventricular systolic dysfunction (RBM20LVSD) were compared with variant-elusive patients with idiopathic left ventricular systolic dysfunction.RESULTS:Longitudinal follow-up data were available for 143 RBM20 variant carriers (71 men; median age, 35.5 years); 7 of 143 had an MVA event at baseline. Thirty of 136 without baseline MVA (22.0%) reached the primary end point, and 16 of 136 (11.8%) had new MVA with no significant difference between men and women (log-rank P=0.07 and P=0.98, respectively). Twenty of 143 (14.0%) developed ESHF (17 men and 3 women; log-rank P<0.001). Four of 10 variant carriers with available LVEF contemporary to MVA had an LVEF >35%. At 5 years, 15 of 67 (22.4%) RBM20LVSD versus 7 of 197 (3.6%) patients with idiopathic left ventricular systolic dysfunction had reached the primary end point (log-rank P<0.001). RBM20 variant carriage conferred a 6.0-fold increase in risk of the primary end point.CONCLUSIONS:RBM20 variants are associated with a high risk of MVA and ESHF compared with idiopathic left ventricular systolic dysfunction. The risk of MVA in male and female RBM20 variant carriers is similar, but male sex is strongly associated with ESHF.

Background/Introduction Enoxaparin and unfractionated heparin (UFH) are guideline-recommended anticoagulants for patients with acute coronary syndrome (ACS) including unstable angina (UA) and myocardial infarction with (STEMI) or without ST-elevation (NSTEMI). Prior efficacy and safety evidence are mainly from clinical trials. Economic data is lacking. Purpose To examine differences in utilization, effectiveness, safety, and costs in treating ACS between enoxaparin and UFH using real-world data. Methods Using Premier Healthcare Database from 859 U.S. hospitals, inpatients 18 years or older with a diagnosis of initial episode of ACS between 2010–2016 were analyzed. Outcomes included 30-day risk of non-fatal myocardial infarction (MI), recurrent angina, in-hospital mortality, composite ischemic complication (having MI/recurrent angina/death), major bleeding, and costs. Multivariable regression was used to compare outcomes between enoxaparin and UFH monotherapy. Results Among 1,048,053 eligible patients (UA: 219,259; NSTEMI: 582,134; STEMI: 246,660), prevalence of enoxaparin monotherapy was 12.0%, 13.9%, and 5.1% and of UFH monotherapy was 45.1%, 43.1% and 59.8% for UA, NSTEMI, and STEMI patients, respectively. Compared to UFH, enoxaparin was associated with lower odds of MI (Adjusted Odds Ratio [OR]=0.95; 95% Confidence Interval (CI): 0.92, 0.99), recurrent angina (OR=0.88; 95% CI: 0.78, 0.98), in-hospital mortality (OR=0.88; 95% CI: 0.81, 0.95) and composite ischemic complications (OR=0.95; 95% CI: 0.92, 0.98) among NSTEMI patients but not in UA or STEMI patients. Enoxaparin was associated with lower odds of major bleeding in all three patients cohorts (UA: OR=0.77, 95% CI: 0.66, 0.91; NSTEMI: OR=0.68; 95% CI: 0.64, 0.72; STEMI: OR=0.72, 95% CI: 0.63, 0.83). Cost savings per patient during index admission and 30-day follow-up for enoxaparin over UFH was $2,813 for UA, $2,332 for NSTEMI and $2,928 for STEMI patients. Conclusions Enoxaparin was associated with lower odds of ischemic complications including death, lower costs and better safety than UFH among NSTEMI patients. Its relative effectiveness varied between patients with different ACS presentations. Improving upstream selection of appropriate anticoagulants in different type of ACS patients has the potential to optimize clinical outcomes and costs. Acknowledgement/Funding This study was funded by Sanofi Inc

Arrhythmic mitral valve prolapse (AMVP) is linked to life-threatening ventricular arrhythmias (VAs), and young women are considered at high risk. Cases of AMVP in women with malignant VA during pregnancy have emerged, but the arrhythmic risk during pregnancy is unknown. The authors aimed to describe features of women with high-risk AMVP who developed malignant VA during the perinatal period and to assess if pregnancy and the postpartum period were associated with a higher risk of malignant VA. This retrospective international multi-centre case series included high-risk women with AMVP who experienced malignant VA and at least one pregnancy. Malignant VA included ventricular fibrillation, sustained ventricular tachycardia, or appropriate shock from an implantable cardioverter defibrillator. The authors compared the incidence of malignant VA in non-pregnant periods and perinatal period; the latter defined as occurring during pregnancy and within 6 months after delivery. The authors included 18 women with AMVP from 11 centres. During 7.5 (interquartile range 5.8-16.6) years of follow-up, 37 malignant VAs occurred, of which 18 were pregnancy related occurring in 13 (72%) unique patients. Pregnancy and 6 months after delivery showed increased incidence rate of malignant VA compared to the non-pregnancy period (univariate incidence rate ratio 2.66, 95% confidence interval 1.23-5.76). The perinatal period could impose increased risk of malignant VA in women with high-risk AMVP. The data may provide general guidance for pre-conception counselling and for nuanced shared decision-making between patients and clinicians.

Association of sustained ventricular arrhythmias with transient myocardial ischemia in patients hospitalized with acute coronary syndrome

Background/Introduction Recently, a variant-specific prediction model for PLN p.Arg14del variant carriers was developed to predict individual malignant ventricular arrhythmia (VA) risk to inform decision-making for primary prevention implantable cardioverter defibrillator (ICD) implantation. This model predicts malignant VA risk from data at diagnosis, but iterative evaluation of malignant VA risk may be warranted considering that the risk factors for malignant VA are progressive. Purpose To evaluate the diagnostic performance of the PLN p.Arg14del risk model. Methods/Results Date were collected of 278 PLN p.Arg14del variant carriers at 3 year follow-up. This was considered the new baseline for the survival analysis. Patients with history of malignant VA at both baseline and during the first 3 years after baseline were excluded. At 3 year patients were aged 40.1±18.0 year and 40.7% was male. Median left ventricular ejection fraction (LVEF) was 53% and percentage with microvoltages was 10.3. During a median follow-up of 4 years (Interquartile range 1.8–6.5) 31 (11%) carriers experienced malignant VA, defined as sustained VA, appropriate ICD intervention, or (aborted) sudden cardiac death. Reevaluation of the predictors with the 3 year follow-up data revealed hazard rates that were similar to those in the original PLN p.Arg14del risk model; LVEF per 1% decrease (hazard ratio (HR) 1.10 [95% confidence interval (CI), 1.06–1.12]; p&amp;lt;0.001), premature ventricular contraction count/24h (HR 1.51 [95% CI, 1.15–1.98]; p=0.003) and the presence of low-voltage electrocardiogram (HR 12.24 [95% CI, 5.21–28.8); p&amp;lt;0.001). Negative T waves did not remain significant as a predictor. The 5-year malignant VA risk was calculated for each variant carrier, after multiple imputation for dealing with incomplete cases, by applying the PLN p.Arg14del risk model to the 3 year follow-up data. Afterwards the cohort was divided into tertiles of predicted risk. This clearly demonstrated the lowest risk tertile having a low malignant VA rate and the highest risk tertile having a high malignant VA rate, which resulted in an optimism-corrected C-statistic of 0.85 (95% CI 0.78–0.92). Conclusion The PLN p.Arg14del risk model is valid at 3 year follow-up in PLN p.Arg14del variant carriers with no history of malignant VA and can therefore be used to inform decision-making for primary prevention ICD implantation not merely at diagnosis, but also during follow-up and can be seen as a type of validation in a cohort where no other large cohort is present to perform external validation. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): 1. PSIDER: From pluripotent stem cells to prime editing gene therapy for inheritedcardiomyopathies. ZOn-MW.2. PREDICT2: Predicting sudden cardiac arrest. The Dutch Heart Foundation.

Background Malignant organic and hereditary ventricular arrhythmias lead to sudden death, accounting for a major death cause of Chinese individuals. Currently, the incidence and risk factors of ventricular arrhythmia remain unclear, and the therapeutics of malignant ventricular arrhythmia require further revising. Rationale The study of the incidence and risk factors of ventricular tachycardia with organic or heritable heart diseases in China will promote early intervention against sudden cardiac death. The improvement of catheter ablation, drug therapies and autonomic nerve intervention will provide patients with lower cost and more efficient diagnosis and treatment strategy. Design The study consists of four parts.①Risk stratification of ventricular tachycardia with organic or heritable heart diseases in China.②Evaluation and intervention strategies of autonomic nervous in ventricular tachycardia of organic heart disease.③Substrate intervention strategy for ventricular arrhythmia.④Demographics, risk stratification and intervention of hereditary malignant ventricular arrhythmia. Conclusion The study will construct the databases for ventricular arrhythmia and multidimensional risk stratification system, predicting the risk of the malignant ventricular arrhythmia and the reciprocal effective interventions. Key words: Ventricular arrhythmia; Risk factors; Catheter ablation; Pharmacological treatment; Autonomic nerve system

The PRAISE (PRedicting with Artificial Intelligence riSk aftEr acute coronary syndrome) score is a machine learning-based model for predicting 1-year adverse cardiovascular or bleeding events in patients with acute coronary syndrome (ACS). Its role in predicting arrhythmic complications in ACS remains unknown. Atrial fibrillation (AF) and ventricular arrhythmias (VA) were recorded by continuous electrocardiographic monitoring until discharge in a cohort of 365 participants with ACS prospectively enrolled. We considered two separate timeframes for VA occurrence: ≤ 48 and > 48 h. The objective was to evaluate the ability of the PRAISE score to identify ACS patients at higher risk of in-hospital arrhythmic complications. ROC curve analysis indicated a significant association between PRAISE score and risk of both AF (AUC 0.89, p = 0.0001; optimal cut-off 5.77%) and VA (AUC 0.69, p = 0.0001; optimal cut-off 2.17%). Based on these thresholds, high/low AF PRAISE score groups and high/low VA PRAISE score groups were created, respectively. Patients with a high AF PRAISE score more frequently developed in-hospital AF (19% vs. 1%). Multivariate analysis showed a high AF PRAISE score risk as an independent predictor of AF (HR 4.30, p = 0.016). Patients with high VA PRAISE scores more frequently developed in-hospital VA (25% vs. 8% for VA ≤ 48 h; 33% vs. 3% for VA > 48 h). Multivariate analysis demonstrated a high VA PRAISE score risk as an independent predictor of both VA ≤ 48 h (HR 2.48, p = 0.032) and VA > 48 h (HR 4.93, p = 0.014). The PRAISE score has a comprehensive ability to identify with high specificity those patients at risk for arrhythmic events during hospitalization for ACS.

Introduction: The phospholamban (PLN) R14del mutation causes dilated and/or arrhythmogenic cardiomyopathy and is associated with an increased risk of malignant ventricular arrhythmias (MVA) and end-stage heart failure. Objectives: To determine risk factors that predict MVA in carriers of PLN R14del and to assess their mortality risk. Methods and results: With non-invasive tools (ECG, echocardiography, Holter, exercise testing, and magnetic resonance imaging), we retrospectively evaluated clinical risk factors for MVA, defined as cardiopulmonary resuscitation (CPR), appropriate ICD treatment, and sudden cardiac death, in a multicenter cohort of 295 PLN R14del carriers. In a median follow-up period of 42 months (interquartile range: 6 to 111 months), 55 (19%) persons experienced a first episode of MVA: 8 persons received successful CPR, 38 received appropriate ICD treatment, and 9 persons died suddenly in the absence of heart failure. The youngest age at which an MVA was observed was 20 years (CPR). Independent risk factors for MVA were non-sustained or sustained ventricular tachycardia and left ventricular ejection fraction <45%, with hazard ratios of 2.4 (95% CI: 1.5–4.5) and 4.0 (95% CI: 1.8–9.1), respectively. In addition, we analyzed all-cause mortality (main outcome measure: standardized mortality ratio [SMR]). All-cause mortality of PLN R14del carriers was increased (SMR 1.7; 95% CI: 1.4–2.0) with significant excess mortality starting from the age of 25 years. Conclusions: Carriers of the PLN R14del mutation are at high risk for MVA and all-cause mortality. Implantation of an ICD could therefore be justified in PLN R14del carriers with a left ventricular ejection fraction <45%, even in the absence of ventricular arrhythmias. Excess mortality is observed starting from the age of 25 years. Cardiological screening of PLN R14del carriers is thus recommended to be initiated at the beginning of adulthood to prevent malignant outcomes.

Risk stratification of sudden cardiac death in patients with coronary artery disease is of great importance. We evaluated the association between ventricular repolarization and induction of malignant ventricular arrhythmias on electrophysiological study of patients with coronary artery disease. A total of 177 patients (65±10.1 years, 83.6% male, mean left ventricular ejection fraction [LVEF] 37.5±13.6%) were analyzed. For each 10 ms increment in the QT interval, there was a 7% increase in malignant ventricular arrhythmias inducibility; QT cutoff point of 452 ms had an accuracy of 0.611 for predicting malignant ventricular arrhythmias (p=0.011). Male gender (odds ratio [OR]=4.18, p=0.012), LVEF <35% (OR=2.32, p=0.013), amiodarone use (OR=2.01, p=0.038), and prolonged QT (OR=1.07, p=0.023) were associated with malignant ventricular arrhythmias. In patients with ventricular dysfunction, QT >452 ms was associated with significantly increased risk of malignant ventricular arrhythmias (OR=5.44, p=0.0004). In those with LVEF ³35%, QT dispersion (QTd) was significantly higher in patients with inducible malignant ventricular arrhythmias. QTd >20 ms had 0.638 accuracy and 81.3% negative predictive value in predicting malignant ventricular arrhythmias. QT interval is an independent factor associated with malignant ventricular arrhythmias in patients with coronary artery disease. The combination of ventricular dysfunction and prolonged QT interval is associated with a 5.44-fold increase of malignant ventricular arrhythmias induction. Male gender, amiodarone use, and decreased left ventricular ejection fraction are also associated with increased risk of inducibility of malignant ventricular arrhythmias on the electrophysiological study.

Modern antithrombotic therapy for acute coronary syndromes rests on a growing body of basic and clinical evidence that rupture or erosion of the surface of a vulnerable plaque sets in motion a sequence of events culminating in thrombus formation in the culprit vessel.1 When the contents of a vulnerable plaque are exposed to the bloodstream, platelets adhere to the subendothelial matrix, release ADP and thromboxane A2, and amplify the generation of thrombin.2 As a result, a platelet aggregate begins to develop. In addition, the coagulation cascade is activated and fibrin strands are formed. Thrombin (factor IIa) plays a pivotal role in the processes described above because of its extensive procoagulant and prothrombotic actions.3 In addition to catalyzing the transformation of soluble fibrinogen into fibrin monomers and activating factor XIII to produce cross-linked fibrin, thrombin promotes clot formation by activating factors V and VIII. It is also one of the most potent agents responsible for platelet adhesion, activation, and aggregation. In vessels with a diseased endothelium, thrombin promotes the release of the vasoconstrictor endothelin 1. Importantly, thrombin also potentiates the proliferative effects of multiple growth factors and is a key mediator of early smooth muscle cell proliferation after arterial injury. There is now abundant evidence that thrombus formation can be prevented by direct or indirect inactivation of thrombin or by inhibition of thrombin production via the intrinsic or extrinsic limbs of the coagulation pathway.3 Unfractionated heparin, the standard antithrombotic agent in clinical practice, is a glycosaminoglycan, consisting of chains of alternating residues of d-glucosamine and uronic acid.4 Although familiar to the vast majority of clinicians, unfractionated heparin has several disadvantages: (1) a variable anticoagulant effect (necessitating frequent monitoring of activated partial thromboplastin time), (2) neutralization by platelet factor 4, (3) less effective inhibition …