Development Of Malignant Ventricular Arrhythmias Research Articles

ECG-only explainable deep learning algorithm predicts the risk for malignant ventricular arrhythmia in phospholamban cardiomyopathy

BackgroundPhospholamban (PLN) p.(Arg14del) variant carriers are at risk for development of malignant ventricular arrhythmia (MVA). Accurate risk stratification allows timely implantation of intracardiac defibrillators and is currently performed with a multimodality prediction model. ObjectiveThis study aimed to investigate whether an explainable deep learning–based approach allows risk prediction with only electrocardiogram (ECG) data. MethodsA total of 679 PLN p.(Arg14del) carriers without MVA at baseline were identified. A deep learning–based variational auto-encoder, trained on 1.1 million ECGs, was used to convert the 12-lead baseline ECG into its FactorECG, a compressed version of the ECG that summarizes it into 32 explainable factors. Prediction models were developed by Cox regression. ResultsThe deep learning–based ECG-only approach was able to predict MVA with a C statistic of 0.79 (95% CI, 0.76–0.83), comparable to the current prediction model (C statistic, 0.83 [95% CI, 0.79–0.88]; P = .054) and outperforming a model based on conventional ECG parameters (low-voltage ECG and negative T waves; C statistic, 0.65 [95% CI, 0.58–0.73]; P < .001). Clinical simulations showed that a 2-step approach, with ECG-only screening followed by a full workup, resulted in 60% less additional diagnostics while outperforming the multimodal prediction model in all patients. A visualization tool was created to provide interactive visualizations (https://pln.ecgx.ai). ConclusionOur deep learning–based algorithm based on ECG data only accurately predicts the occurrence of MVA in PLN p.(Arg14del) carriers, enabling more efficient stratification of patients who need additional diagnostic testing and follow-up.

To predict the left ventricular endocardial scar tissue pattern using Radon descriptor-based machine learning

ObjectiveScar tissue is an identified cause for the development of malignant ventricular arrhythmias in patients of myocardial infarction, which ultimately leads to cardiac death, a fatal outcome. We aim to evaluate the left ventricular endocardial Scar tissue pattern using Radon descriptor-based machine learning. We performed automated Left ventricle (LV) segmentation to find the LV endocardial wall, performed morphological operations, and marked the region of the scar tissue on the endocardial wall of LV. Motivated by a Radon descriptor-based machine learning approach; the patches of 17 patients from Computer tomography (CT) images of the heart were used and categorized into “endocardial Scar tissue” and “normal tissue” groups. The ten feature vectors are extracted from patches using Radon descriptors and fed into a traditional machine learning model.ResultsThe decision tree has shown the best performance with 98.07% accuracy. This study is the first attempt to provide a Radon transform-based machine learning method to distinguish patterns between “endocardial Scar tissue” and “normal tissue” groups. Our proposed research method could be potentially used in advanced interventions.

Association Between Index of Cardio‐Electrophysiological Balance and Cardiac Remodeling

Objective: Pathophysiological changes in response to myocardial infarction (MI) result in cardiac remodeling. Left untreated this pathologic process contributes to impairment of ventricular function and development of malignant ventricular arrhythmias. Recently introduced ECG‐based marker index of cardio‐electrophysiological balance (iCEB) has been shown to be associated with various cardiac conditions. Herein, we aimed to investigate the association between the iCEB and cardiac remodeling in post-MI patients.&#x0D; Materials and Methods: Patients aged ≥18 years presenting with acute MI who underwent successful percutaneous coronary intervention between January 2020 and January 2021 were recruited. Regarding the assessment of cardiac remodeling, left ventricular (LV) mass, LV mass index (LVMI), and relative wall thickness (RWT) were measured before the start of treatment and six months after the procedure along with the QT/QRS ratio (iCEB), and QTC/QRS ratio (iCEBc).&#x0D; Results: According to our study, estimated QT/QRS (iECB) and QTc/QRS (iECBc) ratios were found to be significantly lower at six-month follow-up compared to baseline values (4.73∓0.60 vs 4.62∓0.55 &amp; 4.93∓0.59 vs 4.78∓0.55, p

Early Repolarization, Fragmented QRS and Tpeak-Tend Interval as Electrocardiographic Markers in Patients with Idiopathic Ventricular Arrhythmias: a Brief Review

Introduction: Idiopathic ventricular tachycardia and ventricular fibrillation, as causes of sudden cardiac death, are entities with mechanisms poorly studied and understood to date. The electrocardiogram (ECG) is a simple tool, but with great diagnostic and prognostic value, which has allowed the identification of certain markers associated with increased risk of development of malignant ventricular arrhythmias and sudden cardiac death. Methods: To identify the electrocardiographic markers related to the risk of developing idiopathic malignant ventricular arrhythmias, a review of the literature was performed, looking for the most recent articles with the greatest scientific impact on the topic. Outcome: Although the number of studies published to date is scarce, the published evidence has shown three electrocardiographic risk markers that have emerged in recent years and which have been related to the development of idiopathic malignant ventricular arrhythmias: the early repolarization (ER) pattern, QRS fragmentation (QRSF) and the Tpeak-Tend (Tp-Te) interval. The ECG marker that has shown most evidence to date is the pattern of ER, as a cause of changes in both ventricular depolarization and repolarization. The QRSF and the Tp-Te interval have also been related to the development of idiopathic ventricular arrhythmias, although with less evidence in this regard. Conclusion: In the last years, three electrocardiographic markers have appeared as variables related to the development of malignant ventricular arrhythmias, as is the case of ER, QRSF and Tp-Te interval. However, evidence is scarce in this specific patient profile and further randomized clinical trials are necessary to demonstrate its true relationship and usefulness.

Characteristic Histopathological Findings and Cardiac Arrest Rhythm in Isolated Mitral Valve Prolapse and Sudden Cardiac Death.

BackgroundThe association between mitral valve prolapse (MVP) and sudden death remains controversial. We aimed to describe histopathological changes in individuals with autopsy‐determined isolated MVP (iMVP) and sudden death and document cardiac arrest rhythm.Methods and ResultsThe Australian National Coronial Information System database was used to identify cases of iMVP between 2000 and 2018. Histopathological changes in iMVP and sudden death were compared with 2 control cohorts matched for age, sex, height, and weight (1 group with noncardiac death and 1 group with cardiac death). Data linkage with ambulance services provided cardiac arrest rhythm for iMVP cases. From 77 221 cardiovascular deaths in the National Coronial Information System database, there were 376 cases with MVP. Individual case review yielded 71 cases of iMVP. Mean age was 49±18 years, and 51% were women. Individuals with iMVP had higher cardiac mass (447 g versus 355 g; P<0.001) compared with noncardiac death, but similar cardiac mass (447 g versus 438 g; P=0.64) compared with cardiac death. Individuals with iMVP had larger mitral valve annulus compared with noncardiac death (121 versus 108 mm; P<0.001) and cardiac death (121 versus 110 mm; P=0.002), and more left ventricular fibrosis (79% versus 38%; P<0.001) compared with noncardiac death controls. In those with iMVP and witnessed cardiac arrest, 94% had ventricular fibrillation.ConclusionsIndividuals with iMVP and sudden death have increased cardiac mass, mitral annulus size, and left ventricular fibrosis compared with a matched cohort, with cardiac arrest caused by ventricular fibrillation. The histopathological changes in iMVP may provide the substrate necessary for development of malignant ventricular arrhythmias.

Brugada phenocopies: Current evidence, diagnostic algorithms and a perspective for the future.

Brugada syndrome (BrS) is a congenital channelopathy associated with the development of malignant ventricular arrhythmias and sudden cardiac death. The diagnosis of BrS is made based on Brugada ECG pattern and clinical history. Brugada phenocopies (BrP) are clinical entities that are characterized by ECG patterns identical to those of BrS but arise from different underlying conditions such as metabolic abnormalities, myocardial ischemia and mechanical compression. Distinction between the two is important because BrS requires investigations for risk stratification whereas BrP requires appropriate treatment for the underlying conditions. In the present review, we summarized the current data in the literature, systematic diagnostic approach, gaps in the literature and future perspective on BrP.

Early repolarization pattern in the coronary slow flow phenomenon

Background. The coronary slow flow phenomenon (CSFP) is well-documented, and the early repolarization pattern (ERP) has recently been shown to be a risk factor for the development of malignant ventricular arrhythmias. Methods. Those with true CSFP were included as cases and those with normal angiograms were included as controls. We assessed J-point elevation on surface electrocardiograms (ECGs) and defined ERP as notching or slurring of the terminal portion of the QRS takeoff. Results. We enrolled 115 cases (33 females, 82 males; mean age, 51.9 ± 11.5 years) and 45 controls (13 females, 32 males; mean age, 50.8 ± 11.7 years). ERP was more common among cases than among controls (65% vs. 28%, p = .001). Compared with the controls, cases were more likely to have J-point elevation in the inferior leads (25% vs. 13%, p = .002), in the D1 to aVL leads (22% vs. 15%, p = .001), and in the lateral leads (17.3% vs. 0%), p = .001). Notching was also significantly more common in cases than in controls (26.0% vs. 2.2%, p = .0001). Finally, concave/ascendant ST segment (33.9% vs. 5.2%, p = .006), horizontal/non-ascendant ST segment (14.7% vs. 1.7%, p = .054), and horizontal/non-ascendant ST segment and notching (15.6% vs. 2.2%, p = .012) patterns were more common in cases than in controls. Conclusions. We report that CSFP is associated with J-wave and slurring ERPs. However, the clinical significance of these changes needs to be clarified.

Sleep-disordered breathing is associated with disturbed cardiac repolarization in patients with a coronary artery bypass graft surgery

BackgroundThe development of malignant ventricular arrhythmias due to abnormal cardiac repolarization is a major complication after coronary artery bypass graft surgery (CABG). Sleep-disordered breathing (SDB) is linked to prolonged cardiac repolarization in non-surgical patients. This study evaluates cardiac repolarization in patients with and without SDB who underwent CABG. Methods100 patients who had received CABG (84% men, age 68 ± 10 years, body-mass-index [BMI] 28.7 ± 4.2 kg/m2) were retrospectively evaluated. Polygraphy was recorded the night before CABG. SDB was defined as an apnea-hypopnea index (AHI) of ≥15/h and differentiated into central (CSA) and obstructive (OSA) sleep apnea. Cardiac repolarization was assessed by means of T-peak-to-end (TpTe) and QTc-intervals and TpTe/QT-ratios derived from 12-lead electrocardiography (ECG). Results37% of patients had SDB, 14% CSA and 23% OSA. Before CABG, patients with CSA and OSA had longer TpTe intervals than those without SDB (TpTe: CSA 100 ± 26 vs. OSA 97 ± 19 vs. no SDB 85 ± 14 ms, p = 0.013). QTc intervals and TpTe/QT ratios differed between the two groups (QTc: 444 ± 54 vs. 462 ± 36 vs. 421 ± 32 ms, p < 0.001; TpTe/QT ratio: 0.24 ± 0.04 vs. 0.23 ± 0.05 vs. 0.21 ± 0.03, p = 0.045). SDB was associated with abnormal cardiac repolarization independent of known risk factors for cardiac arrhythmias, such as age, sex, BMI, N-terminal-pro-brain-natriuretic-peptide (NT-proBNP), and heart failure (TpTe: B-coefficient [95%CI]: 16.0, [7.6–24.3], p < 0.001; QTc: 27.2 [9.3–45.1], p = 0.003; TpTe/QT ratio: 2.9 [1.2–4.6], p < 0.001). ConclusionIndependent of known risk factors for cardiac arrhythmias, SDB was significantly associated with abnormal cardiac repolarization before CABG. Data suggest that SDB may contribute to an increased risk of ventricular arrhythmias after CABG.

Ventricular arrhythmias and sudden cardiac death

### Key points There are 50–100 unexpected, sudden cardiac deaths (SCDs) per 100 000 population per year in Europe and USA, categorized by symptom onset to cardiac arrest time of <1 h.1 Despite the decline in coronary artery disease mortality and advancements in resuscitation services, survival from these events remains low. Unfortunately, they often occur outside the hospital environment and are associated with a survival rate of <10%. The majority occur in adults over 35 yr of age and at least half of these events can be attributed to ventricular arrhythmias, although the true incidence is unknown due to inevitable degeneration to asystole if unwitnessed. These arrhythmias may be the presenting complaint in the emergency department and may feature throughout the perioperative period, including at preoperative assessment, during surgery and in the recovery phase, for example in intensive care. They may also be the direct target of therapy in the case of electrophysiological catheter ablation and implantable cardioverter defibrillators (ICDs). They are more frequent and carry greater risks in patients with structural heart disease, but younger patients with ion-channel abnormalities can also be susceptible.2 This review classifies the causes and significance of ventricular arrhythmias based on the presence or absence of structural heart disease and provides a simple system to aid confident distinction from supraventricular arrhythmias. …

Potential pro-arrhythmic effect of cardiac resynchronization therapy

A decline in mortality due to pump failure has been clearly documented after cardiac resynchronization therapy (CRT), however the impact on sudden cardiac death and the development of malignant ventricular arrhythmias remains questionable. Our study aims to investigate this alleged pro-arrhythmic effect of CRT using surface electrocardiogram (ECG) markers of pro-arrhythmia. MethodsSeventy five patients, who received CRT were included in this study. Manual measurement of corrected QT interval (QTc), Tpeak-end (Tp-e) interval, QT dispersion (QTd) and Tpeak-end dispersion during baseline 12 lead surface ECG and after applying atrial-biventricular pacing were done. Arrhythmias post CRT was recorded from ECG, 24h holter monitoring or pacemaker programmer event recorder. ResultsQTc interval showed significant prolongation after CRT (498.9±50.8 vs. 476.2±41.6msec, P=0.0001). Comparing patients with major arrhythmogenic events (MAE) and increased frequency of premature ventricular contractions (PVCs) post CRT pacing to those patients without arrhythmias, there was a significant prolongation of the QTc interval (527±63.29 vs. 496.95±45.2msec, P=0.043) and Tp-e interval (94.16±9 vs. 87.41±16.37msec, P=0.049). While in the arrhythmogenic group, there was an insignificant decrease in QTd and Tpeak-end dispersion. ConclusionQTc and Tp-e intervals are a potential predictor of occurrence of MAE and PVCs. On the other hand, Tp-e dispersion and QTd did not show a predictive potential for arrhythmia.

The acute inotropic effects of cardiac contractility modulation (CCM) are associated with action potential duration shortening and mediated by β1-adrenoceptor signalling

Despite promising results in clinical trials conducted to date, little is known about how cardiac contractile modulation (CCM) mediated inotropic enhancement occurs and how CCM affects the electrophysiological characteristics of the heart. The aims of the present study were to 1) investigate how the stimulation parameters of the CCM signal and the location of stimulus delivery influence the contractile response, 2) characterise the effect of CCM on ventricular electrophysiology, and 3) investigate the potential physiological mechanisms underlying these acute inotropic and electrophysiological effects. Experiments were conducted in isolated rabbit hearts with simultaneous measurement of ventricular contractility and monophasic action potential duration (MAPD). Biphasic square wave pulses were applied to the left ventricle, timed to coincide with the absolute refractory period. CCM mediated responses were assessed over a range of signal amplitudes (2–30mA), durations (2–15ms) and delays from the activation of the locally recorded monophasic action potential (0–30ms). Responses were assessed during perfusion with the β1-adrenoceptor antagonist metoprolol (1.8μM) and HMR 1556 (500nM), an inhibitor of the slow delayed rectifying potassium current. Norepinephrine content was collected and assessed by ELISA from samples of coronary effluent collected during CCM. CCM induced a significant increase in left ventricular pressure (LVP) in a manner dependent upon the amplitude and duration of the CCM signal but independent of the delay of the stimulus within the action potential plateau and was associated with an increase in norepinephrine in coronary effluent (Mean: 46±9pg/ml). CCM promoted a shortening of MAPD-90% close to the site of stimulation (−19±3%) but had no effect on those recorded at distant sites (0±1%). The increase in LVP (4.7±1.8 vs. 0.7±0.9%, P<0.01) and shortening of local MAPD-90% (−15±3 vs. 1±1%, P<0.01) was abolished with metoprolol. Perfusion with HMR 1556 caused a significant inhibition of local MAPD shortening (−27±2 vs. −21±3ms, P<0.05). CCM is associated with a shortening of ventricular MAPD in a manner dependent upon β-adrenoceptor stimulation resulting from catecholamine release, a finding which may be of clinical significance in regard to the development of malignant ventricular arrhythmias. This article is part of a Special Issue entitled Possible Editorial.

Impact of Systemic Acidosis on the Development of Malignant Ventricular Arrhythmias After Reperfusion Therapy for ST-Elevation Myocardial Infarction

The aim of the present study was to examine the effect of systemic acidosis on the development of malignant ventricular arrhythmias, including sustained ventricular tachycardia and ventricular fibrillation (VT/VF), after reperfused ST-elevation myocardial infarction (STEMI). A total of 157 consecutive patients with a reperfused STEMI were examined. Patients were divided into 2 groups according to the presence or absence of systemic acidosis, defined as arterial blood pH <7.40 on admission. Serum creatine kinase and C-reactive protein (CRP) levels were serially measured. Systemic acidosis was observed in 53 patients (34%). There was no significant difference in coronary risk factors and arrival time from onset between the 2 groups. Estimated glomerular filtration rate (eGFR) on admission was lower in patients with acidosis than in those without (P=0.001). Patients with acidosis had a higher incidence of VT/VF (26% vs 4%, P<0.0001), especially within 48 h after STEMI (23% vs 3%, P=0.0002), than those without. The peripheral white blood cell count on admission was higher in patients with than in those without acidosis. Multivariate analysis showed that systemic acidosis was a strong independent predictor of VT/VF (relative risk =8.79, P=0.002) among variables including prior MI and eGFR <60 ml . min(-1) . 1.73 m(-2). Systemic acidosis was a significant determinant of VT/VF after reperfused STEMI and was associated with elevated serum CRP level. Systemic acidosis and subsequent inflammation after ischemia reperfusion may play an important role in the development of VT/VF.

Role of Ischemic Preconditioning and Inflammatory Response in the Development of Malignant Ventricular Arrhythmias After Reperfused ST-Elevation Myocardial Infarction

Background Sustained ventricular tachycardia and ventricular fibrillation (VT/VF) are major complications of ST-elevation myocardial infarction (STEMI), even in the era of reperfusion therapy. We sought to clarify the determinants of VT/VF after reperfused STEMI. Methods and Results Consecutive STEMI patients treated with primary percutaneous coronary intervention (n = 457) were divided into 2 groups by the presence or absence of VT/VF during hospitalization. Serum C-reactive protein (CRP) level and peripheral white blood cell (WBC) count were serially measured. VT/VF was observed in 54 patients (12%). Prior infarction was more common and preinfarction angina was less in patients with VT/VF than those without. Peak CRP level ( P < .0001), WBC count on admission ( P = .008), and maximum WBC count ( P = .0014) were higher in patients with VT/VF than those without. VT/VF, especially VT/VF later than 48 hours after onset, was associated with greater left ventricular (LV) dimension during convalescence. Kaplan-Meier curves and log-rank test revealed VT/VF to be a significant determinant of long-term major adverse cardiac events. Multivariate analysis revealed that prior infarction, absence of preinfarction angina, and peak CRP ≥10 mg/dL were independent determinants of VT/VF. Conclusions Lack of ischemic preconditioning, enhanced inflammatory response, and subsequent LV dysfunction are related to the development of VT/VF after STEMI.

Abstract 3207: Role of Ischemic Preconditioning and Inflammatory Response in the Development of Malignant Ventricular Arrhythmias after Reperfused Acute Myocardial Infarction

Background: Malignant ventricular arrhythmias, such as sustained ventricular tachycardia and ventricular fibrillation (VT/VF), are fatal complications after acute myocardial infarction (MI) even in the era of reperfusion therapies. We sought to clarify the determinants of VT/VF after reperfused MI. Methods: A total of 528 consecutive acute MI patients, who were treated with primary percutaneous coronary intervention, were divided into 2 groups according to the presence or absence of VT/VF during hospitalization. Serum C-reactive protein (CRP) level and peripheral white blood cell (WBC) count were serially measured for every 24 hours. As a substudy, left ventricular (LV) function and long-term clinical outcome were compared between patients with early (&gt;48 hours after the onset) and late VT/VF (&gt;48 hours). Results: VT/VF was observed in 58 patients (11%). Prior MI and anterior MI are more common in patients with VT/VF than those without. Prevalence of preinfarction angina was less in patients with VT/VF than those without. Peak CRP (14.7±10.1 vs. 8.8±7.1 mg/dl, p&lt; 0.0001), WBC on admission (12833±3513 vs. 10906±4771 /mm 3 , p=0.03) and maximum WBC (14808±5335 vs. 12531±4348 /mm 3 , p=0.009) were higher in patients with VT/VF than those without. Multivariate analysis revealed that prior MI (RR=4.57, p=0.02), absence of preinfarction angina (RR=2.44, p=0.02) and peak serum CRP ≥10 mg/dl (RR=3.37, p=0.003) were independent determinants of VT/VF. Early VT/VF was observed in 49 patients, while late VT/VF in 9 patients. Prevalence of prior MI, preinfarction angina or peak CRP ≥10mg/dl was comparable between early and late VT/VF. LV end-diastolic and end-systolic dimensions are greater in patients with late VT/VF than those with early VT/VF (p&lt; 0.05). Incidence of readmission for heart failure and sudden cardiac death tended to be higher in patients with late VT/VF than those with early VT/VF. Conclusions: VT/VF after reperfused acute MI was associated with prior history of MI, absence of preinfarction angina and increased inflammatory markers. VT/VF occurred in late phase was related to depressed LV function. Lack of ischemic preconditioning, enhanced inflammatory response and subsequent LV remodeling could contribute to the development of VT/VF after MI.

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

Background: Myocardial ischemia is a known substrate for the development of malignant ventricular arrhythmias. Purpose: The purpose of this secondary analysis was to determine the occurrence of ventricular arrhythmias at the time of transient myocardial ischemia in patients hospitalized with acute coronary syndrome (ACS). Methods: Patients who presented to the emergency department at the San Francisco Medical Center, University of California, San Francisco, Calif, with chest pain or anginal equivalent were enrolled in a prospective study involving 12-lead electrocardiogram Holter ST-segment monitoring. Transient myocardial ischemia was defined as a change in ST-segment amplitude of 200 lV or greater in 1 lead or more or 100 lV or greater in 2 leads or more, lasting for at least 60 seconds. An associated arrhythmia was defined as sustained ventricular tachycardia (VT) or ventricular fibrillation during or 10 minutes before or after an ST event. Results: One thousand one hundred thirty-six (emergency department) patients evaluated for chest pain/anginal equivalent were monitored for 24 hours. Of these, 270 patients were hospitalized with a diagnosis of ACS (acute myocardial infarction, n = 95; unstable angina, n = 175). Of the 270 patients, 31 (11%) had a total of 44 STevents (number, 1.4F 1.6; range, 1-10; duration, 27 F 15 minutes). Of the 44 ST events, 24 (55%) had an isolated premature ventricular contraction or ventricular couplet; however, none had associated sustained VT/ventricular fibrillation. The figure below shows the longest sustained arrhythmia (9-beat VT) among the 31 patients, and it occurred in the absence of electrocardiogram signs of ischemia. Conclusions:With current medical management, frequency of ischemia is low in patients hospitalized with ACS, and malignant ventricular arrhythmias were not observed in this cohort.

Left Ventricular Epicardial Activation Increases Transmural Dispersion of Repolarization in Healthy, Long QT, and Dilated Cardiomyopathy Dogs

Benefits of cardiac resynchronization therapy (CRT) are well established. However, less is understood concerning its effects on myocardial repolarization and the potential proarrhythmic risk. Healthy dogs (n = 8) were compared to a long QT interval (LQT) model (n = 8, induced by cesium chloride, CsCl) and a dilated cardiomyopathy with congestive heart failure (DCM-CHF, induced by rapid ventricular pacing, n = 5). Monophasic action potential (MAP) recordings were obtained from the subendocardium, midmyocardium, subepicardium, and the transmural dispersion of repolarization (TDR) was calculated. The QT interval and the interval from the peak to the end of the T wave (T(p-e)) were measured. All these characteristics were compared during left ventricular epicardial (LV-Epi), right ventricular endocardial (RV-Endo), and biventricular (Bi-V) pacing. In healthy dogs, TDR prolonged to 37.54 ms for Bi-V pacing and to 47.16 ms for LV-Epi pacing as compared to 26.75 ms for RV-Endo pacing (P < 0.001), which was parallel to an augmentation in T(p-e) interval (Bi-V pacing, 64.29 ms; LV-Epi pacing, 57.89 ms; RV-Endo pacing, 50.29 ms; P < 0.01). During CsCl exposure, Bi-V and LV-Epi pacing prolonged MAPD, TDR, and T(p-e) interval as compared to RV-Endo pacing. The midmyocardial MAPD (276.30 ms vs 257.35 ms, P < 0.0001) and TDR (33.80 ms vs 27.58 ms, P=0.002) were significantly longer in DCM-CHF dogs than those in healthy dogs. LV-Epi and Bi-V pacing further prolonged the MAPD and TDR in this model. LV-Epi and Bi-V pacing result in prolongation of ventricular repolarization time, and increase of TDR accounted for a parallel augmentation of the T(p-e) interval, which provides evidence that T(p-e) interval accurately represents TDR. These effects are magnified in the LQT and DCM-CHF canine models in addition to their intrinsic transmural heterogeneity in the intact heart. This mechanism may contribute to the development of malignant ventricular arrhythmias, such as torsades de pointes (TdP) in congestive heart failure (CHF) patients treated with CRT.

The development of malignant ventricular arrhythmia in patients with ischemic cardiomyopathy and the prognostic significance of NT-PROBNP

The development of malignant ventricular arrhythmia in patients with ischemic cardiomyopathy and the prognostic significance of NT-PROBNP

P-072 The development of malignant ventricular arrhythmia in patients with ischemic cardiomyopathy and the prognostic significance of NT-proBNP

P-072 The development of malignant ventricular arrhythmia in patients with ischemic cardiomyopathy and the prognostic significance of NT-proBNP

P-072 The development of malignant ventricular arrhythmia in patients with ischemic cardiomyopathy and the prognostic significance of NT-proBNP

Purpose A significant new cardiac marker in the prognosis of ischemic cardiomyopathy N-terminal pro brain natriuretic peptide (NT-proBNP) has recently been reported. Given the high incidence of sudden death in patients with congestive heart failure we examined the value of NT-proBNP in predicting the occurrence of malignant arrhythmias in patients with implantable cardioverter-defibrillators. Methods Baseline plasma concentrations of NT-proBNP were measured using ELISA in 25 patients (mean age 66±8 years) with ischemic cardiomyopathy and a left ventricular ejection fraction ≤35%. In all patients an internal cardioverter-defibrillator had been implanted for primary prevention of sudden death according to MADIT I criteria. Results The implantable cardiac defibrillators were interrogated at 1-year follow-up to identify the type of arrhythmias patients had developed. NT-proBNP concentrations were significantly higher in patients who developed sustained monomorphic ventricular tachycardia (SVT) or ventricular fibrillation (VF) compared with those having only episodes of non-sustained ventricular tachycardia (NSVT), (1024 ± 462 vs. 675 ± 320 pmol/L). By regression analysis, NT-proBNP was found to be a powerful predictor of sustained monomorphic ventricular tachycardia (R=0.423, p=0.035). Conclusion Increased circulating levels of NT-proBNP predict the appearance of sustained ventricular tachycardia and may serve as an additional criterion defining patients at high risk for sudden cardiac death.

Antiarrhythmic efficacy of combined I(Ks) and beta-adrenergic receptor blockade.

Suppression of malignant ventricular arrhythmias by selective blockade of the cardiac slowly activating delayed rectifier current (I(Ks)) has been demonstrated with the benzodiazepine L-768673 [(R)-2-(2,4-trifluoromethyl-phenyl)-N-[2-oxo-5-phenyl-1-(2,2,2-trifluoro-ethyl)-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl]acetamide] in canine models of recent and healed myocardial infarction. The present study extends the initial antiarrhythmic assessment of I(Ks) blockade by demonstrating prevention of ischemic malignant arrhythmias in dogs with recent (8.0 +/- 0.4 days) anterior myocardial infarction with the coadministration of a subeffective dose of L-768673 and a subeffective, minimally beta-adrenergic blocking dose of timolol. Administered individually, neither 0.3 microg/kg i.v. L-768673 nor 1.0 microg/kg i.v. timolol prevented the induction of ventricular tachyarrhythmia (VT) by programmed ventricular stimulation (PVS) or the development of malignant ventricular arrhythmia in response to acute coronary artery thrombosis. In contrast, coadministration of 0.3 microg/kg i.v. L-768673 + 1.0 microg/kg i.v. timolol suppressed the induction of VT by PVS (8/10, 80% rendered noninducible versus 1/10, 10% noninducible in vehicle group; p < 0.01) and prevented the development of acute ischemic lethal arrhythmias (3/10, 30% incidence versus 8/10, 80% incidence in vehicle group; p < 0.05). Concomitant administration of low-dose L-768673 + timolol produced modest increases in QTc and paced QT intervals (4.5 +/- 1.2 and 5.5 +/- 1.4%; both p < 0.01), increases in noninfarct zone relative and effective refractory periods (7.0 +/- 1.7 and 12.3 +/- 3.0%; both p < 0.01), and lesser increases in infarct zone relative and effective refractory periods (5.3 +/- 1.6 and 5.8 +/- 1.4%; both p < 0.01). These findings suggest that concomitant low-dose I(Ks) and beta-adrenergic blockade may constitute a potential pharmacologic strategy for prevention of malignant ischemic ventricular arrhythmias.