Occurrence Of Life-threatening Ventricular Arrhythmias Research Articles

Genotype is associated with left ventricular reverse remodelling and early events in recent-onset dilated cardiomyopathy.

Recent-onset dilated cardiomyopathy (RODCM) is characterized by heterogeneous aetiology and diverse clinical outcomes, with scarce data on genotype-phenotype correlates. Our aim was to correlate individual RODCM genotypes with left ventricular reverse remodelling (LVRR) and clinical outcomes. In this prospective study, a total of 386 Czech RODCM patients with symptom duration ≤6months underwent genetic counselling and whole-exome sequencing (WES). The presence of pathogenic (class 5) or likely pathogenic (class 4) variants in a set of 72 cardiomyopathy-related genes was correlated with the occurrence of all-cause death, heart transplantation, or implantation of a ventricular assist device (primary outcome) and/or ventricular arrhythmia event (secondary outcome). LVRR was defined as an improvement of left ventricular ejection fraction to >50% or ≥10% absolute increase, with a left ventricular end-diastolic diameter ≤33mm/m2 or ≥10% relative decrease. Median follow-up was 41months. RODCM was familial in 98 (25%) individuals. Class 4-5 variants of interest (VOIs) were identified in 125 (32%) cases, with 69 (18%) having a single titin-truncating variant (TTNtv) and 56 (14%) having non-titin (non-TTN) VOIs. The presence of class 4-5 non-TTN VOIs, but not of TTNtv, heralded a lower probability of 12-month LVRR and proved to be an independent baseline predictor both of the primary and the secondary outcome. The negative result of genetic testing was a strong protective baseline variable against occurrence of life-threatening ventricular arrhythmias. Detection of class 4-5 VOIs in genes coding nuclear envelope proteins was another independent predictor of both study outcomes at baseline and also of life-threatening ventricular arrhythmias after 12months. Class 4-5 VOIs of genes coding cytoskeleton were associated with an increased risk of life-threatening ventricular arrhythmias after baseline assessment. A positive family history of dilated cardiomyopathy alone only related to a lower probability of LVRR at 12months and at the final follow-up. RODCM patients harbouring class 4-5 non-TTN VOIs are at higher risk of progressive heart failure and life-threatening ventricular arrhythmias. Genotyping may improve their early risk stratification at baseline assessment.

Dynamics of Non-Invasive Risk Factors of Sudden Cardiac Death after Myocardial Revascularization

Background: An attempt was made to study the effect of surgical myocardial revascularization on the processes of electrical myocardium instability underlying the occurrence of life-threatening ventricular arrhythmias, as well as the possibility of its non-invasive assessment by studying heart rate variability (HRV) and heart rate turbulence (HRT), as well as the duration and dispersion of the QT interval. Based only on the presence of viable myocardium, it is often impossible to predict the positive impact of revascularization on a patient’s prognosis, especially with reduced myocardial contractility. Moreover, given the well-studied relationship between myocardial remodeling and neurohormonal activation, non-invasive methods for assessing the autonomic regulation of cardiac activity can provide additional diagnostic information. Along with this, changes in these indicators and their prognostic role in patients with coronary artery disease after revascularization are subjects of discussion. Methods and Results: All patients underwent a comprehensive clinical and biochemical blood test, transthoracic echocardiography, tissue Doppler echocardiography, ultrasound examination of brachiocephalic arteries, selective coronary angio- and ventriculography, as well as Holter monitoring. Results show that a year after the coronary intervention, there was a significant positive trend in the frequency and structure of ventricular arrhythmias (VA). HRV indicators generally did not show significant dynamics. Only an increase in the values of the SDANN and low-frequency power (LFP) indices was noted, indicating a gradual increase in the activity of the sympathetic part of the autonomic nervous system. HRT indicators also did not show significant dynamics. A significant increase was found in the number of patients with no signs of impaired HRT. The average duration of the QT interval decreased significantly. There was also a tendency to shorten the corrected QT interval; however, it was insignificant. In terms of dispersion, both the QT interval and its corrected index, no significant dynamics were recorded in the general group of patients. Conclusion: Our study found that in patients with prior myocardial infarction, after revascularization, significant positive dynamics were recorded in life-threatening ventricular arrhythmias, but were unreliable for the indicators of autonomic regulation of cardiac activity, such as HRV and HRT.

104 EFFECTIVENESS OF 2014 ESC HCM RISK-SCD SCORE IN PREDICTION OF APPROPRIATE ICD SHOCK

Abstract Background Since 2014, European Guidelines have recommended using a novel clinical risk prediction model, called the HCM Risk-SCD, to identify which patients with hypertrophic cardiomyopathy (HCM) who are at higher risk for sudden cardiac death (SCD) and would benefit most from having a prophylactic cardioverter defibrillator (ICD) implantable. In recent years, evidence has called into question the effectiveness of this model in patient selection. Material and Methods Data from consecutive patients with HCM and ICD who were followed at our Cardiology Department from January 2000 to January 2022 were retrospectively collected. Results Among 702 HCM patients, 52 (7%) received an ICD (female, 31%; mean age at implantation, 49 ± 20; S-ICD, 13%; single-chamber ICD, 50%). Of them, 7 (13%) patients were implanted for secondary prevention while 45 (87%) for primary prevention. Out of the 45 primary prevention patients, 7 (16%) experienced 8 appropriate shocks (AS) while 10 (22%) had 15 inappropriate shocks (IS), during a mean follow up of 8 ± 5 years. Overall, mean HCM Risk-SCD score was 6.8 ± 4.7. Patients with AS showed a non-significant higher risk score when compared to non-AS subjects (7.1 ± 5.4 vs 4.8 ± 5.1, p=0.27). By stratifying study population according to pre-established and clinically adopted HCM Risk-SCD score cut-off (such as < 4 vs. > or = 4), we failed to highlight any significant difference in term of AS between groups. Indeed, out of 10 (22%) patients with HCM Risk-SCD score < 4, 3 (7%) experienced AS, while among 35 (78%) patients with HCM Risk-SCD score > or = 4, 4 (9%) had AS (30% vs. 11%, p=0.17). Conclusions The HCM Risk-SCD score does not seem to be able to predict the occurrence of life-threatening ventricular arrhythmias and AS in HCM patients. Our data highlight the need to elaborate a new score in order to improve SCD risk stratification and better select patients for ICD implantation.

47CRT-D versus CRT-P: are we on the right track?

Abstract Introduction Implantable cardioverter defibrillators (ICD) and cardiac resynchronisation therapy (CRT) have both proven to reduce mortality in patients with heart failure (HF). However, randomised trials comparing CRT-pacemaker (CRT-P) vs CRT-defibrillator (CRT-D) are lacking. Understanding a patient’s primary mode of death is therefore important as this may guide the proper use of CRT systems and avoid risks that are associated with under -or overtreatment with an ICD. Purpose This study aims to analyse the mode of death and the occurrence of life-threatening ventricular arrhythmias (VAs) in patients who received a CRT-P or CRT-D. This may help in the future selection for an appropriate cardiac device in patients with HF. Methods Patients with HF undergoing CRT-P or CRT-D implantation in a tertiary hospital between January 2008 and December 2018 were retrospectively evaluated. CRT indications were in compliance with the ESC guidelines. The decision to implant CRT-D or CRT-P in primary prevention was left at the discretion of the treating physician but was based on ESC clinical guidance. Life threatening VAs (sustained ventricular tachycardia > 30s not requiring therapy or appropriate therapy for VAs) and mode of death were analysed. Results 511 patients were implanted with a CRT (CRT-D/CRT-P; n = 311/200) of which 410 (CRT-D/CRT-P; n= 245/165) were followed in our centre for 63,5 ± 38,1 months. Patients with CRT-P were older (77,6 ± 8,1 vs 66,8 ± 9,5 years; p <0,001), more often female (39,4 vs 26,9%; p 0,006), had more a non-ischaemic cause (61,2 vs 44,9%; p 0,001) and a significant higher comorbidity burden. They also received less treatment with neurohumoral blockers. Baseline LVEF was higher in the CRT-P group (33,1 ± 8,9 vs 28,0 ± 7,6%, p <0,001). 6 months follow-up showed a similar increase in LVEF in the CRT-P vs CRT-D group (+10,3 ± 9,6 vs +11,4 ± 10,8%, p 0,38). Main reasons to choose for CRT-P were RV-pacing induced cardiomyopathy (CMP) (26,1%), multiple comorbidities (18,8%), HF complicated by high degree AV block or AV junction ablation (18,2%), non-ischaemic CMP with suspected good CRT response (10,3%), age (7,3%), other (19,3%). 6/165 patients with CRT-P (3,6%), of which 5 were detected by remoted telemonitoring, vs 51/245 with CRT-D (20,8%) experienced episodes of life-threatening arrhythmias (p <0,001). All-cause mortality was higher in the CRT-P vs CRT-D group (36,4 vs 25,3%, p 0,005). However, the CRT-P group had a predominant non-cardiac mode of death (70,9 vs 43,3%, p <0,001). Death secondary to a tachyarrhythmic event was present in only 1 patient (1,7%) in the CRT-P group. Conclusions Guided by clinical parameters and presence of competitive non-cardiac causes of death, adequate decision between CRT-P or CRT-D implantation can be made. In our cohort, sudden cardiac death in the CRT-P group occurred only once. Remote monitoring is able to identify a subgroup of patients potentially benefiting from an upgrade from CRT-P to CRT-D.

P6329123-Iodine Metaiodobenzylguanitidine imaging: a useful prognostic marker of cardiovascular death in heart failure patients

Abstract Background According to guidelines, implantable cardioverter defibrillator (ICD) is recommended in prevention of sudden cardiac death (SCD) in heart failure (HF) patients (pts). Guidelines have several limitations because ICD indication is based mainly on left ventricular ejection fraction (LVEF). Recently, 123-iodine metaiodobenzylguanidine imaging (123-I MIBG) seems to identify, independently from LVEF, pts at high risk of SCD: heart/mediastinum (H/M) ratio<1.6 and summed score (SS)>26. Purpose The aim is to assess the role of 123-I MIBG to predict malignant ventricular arrhythmias (VA) in HF pts Methods We enrolled 208 pts, admitted to our hospital with diagnosis of HF and LVEF≤35%, NYHA class II and III, who underwent 123-I MIBG imaging. H/M ratio of 1.6 was used as a cut-off to identify high risk (G1) versus low risk pts (G2). All pts underwent ICD implantation. Follow-up was performed at 24 months. Results 138 patients were included in G1 and 70 patients in G2. All baseline characteristics were similar in the two groups (table 1). At 24 months follow-up VA events were recorded greater in G1 compared to G2 (21% vs 10%, p=0.04). Table 1 G1 G2 P value H/M ≤1.6 (N=138) H/M >1.6 (N=70) Age (years) 65±12 63±14 0.28 Male, N (%) 108 (78) 64 (91) 0.02 Diabetes mellitus type II, N (%) 54 (39) 14 (20) 0.01 Dyslipidemia, N (%) 58 (42) 30 (42) 0.64 LVEF (%) 30±5 31±4 0.14 Ischaemic CM, N (%) 85 (62) 30 (42) 0.012 Malignant VA, N (%) 30 (21) 7 (10) 0.04 SS 38±9 16±7 0.0001 H/M: heart mediastinum ratio; LVEF: left ventricular ejection fraction; CM: cardiomyopathy; VA: ventricular arrhythmias; SS: summed score. Conclusion Our results seem to confirm that 123-I MIBG uptake is associated with the occurrence of life-threatening VA in HF pts independently from LVEF. The use of 123-I MIBG could be a useful tool in the future to increase the specificity of the pts selection for ICD therapy.

Machine learning approach to recognize ventricular arrhythmias using VMD based features

The occurrence of life-threatening ventricular arrhythmias (VAs) such as Ventricular tachycardia (VT) and Ventricular fibrillation (VF) leads to sudden cardiac death which requires detection at an early stage. The main aim of this work is to develop an automated system using machine learning tool for accurate prediction of VAs that may reduce the mortality rate. In this paper, a novel method using variational mode decomposition (VMD) based features and C4.5 classifier for detection of ventricular arrhythmias is presented. The VMD model was used to decompose the electrocardiography (ECG) signals to extract useful informative features. The method was tested for ECG signals obtained from PhysioNet database. Two standard databases i.e. CUDB (Creighton University Ventricular Tachyarrhythmia Database) and VFDB (MIT-BIH Malignant Ventricular Ectopy Database) were considered for this work. A set of time–frequency features were extracted and ranked by the gain ratio attribute evaluation method. The ranked features are subjected to support vector machine (SVM) and C4.5 classifier for classification of normal, VT and VF classes. The best detection was obtained with sensitivity of 97.97%, specificity of 99.15%, and accuracy of 99.18% for C4.5 classifier with a 5 s data analysis window. These results were better than SVM classifier result having an average accuracy of 86.87%. Hence, the proposed method demonstrates the efficiency in detecting the life-threatening VAs and can serve as an assistive tool to clinicians in the diagnosis process.

Association between premature ventricular complexes during exercise, long-term occurrence of life-threatening arrhythmia and mortality.

Exercise-induced premature ventricular complexes (EiPVCs) are often considered as benign arrhythmias, although they are associated with a high risk of all-cause death in the general healthy population. However, an intermediate pathophysiological process remains unclear, particularly in patients with known cardiovascular disease. The aim of this study was to find an association between EiPVCs, the occurrence of life-threatening ventricular arrhythmias (LACO), and all-cause mortality in patients with cardiovascular disease. This was an observational study of a cohort of patients with coronary artery disease (CAD) or idiopathic cardiomyopathy (ICM). Stress testing was performed as a part of the routine cardiovascular evaluation. The occurrence of EiPVCs was evaluated during exercise testing (ET). At follow-up, long-term occurrence of LACO was evaluated. A bivariate and multivariate analysis was performed. Out of the total of 1442 patients analysed, 700 (49%) had EiPVCs. During 14 years of following-up after ET, 106 LACO outcomes were observed. Long-term all-cause mortality was 4% (n=61). A bivariate analysis showed that patients with EiPVCs had an increased risk for LACO (RR=2.81, 95% CI; 1.9-4.3, P<.001), and for mortality (RR=2.1, CI95% 1.2-3.4, P<.01). Occurrence of LACO was also associated with a higher mortality risk (RR=5.7, 95% CI; 3.4-9.4, P<.001). After a post hoc analysis, LACO remained as a highly predictive variable for mortality. Patients with EiPVCs have a high risk of LACO and all-cause mortality. The presence of LACO could be an intermediate stage between EiPVCs and mortality in subjects with cardiovascular disease.

The Ser96Ala variant in histidine-rich calcium-binding protein is associated with life-threatening ventricular arrhythmias in idiopathic dilated cardiomyopathy

AimsTo investigate whether genetic variants of the histidine-rich calcium (HRC)-binding protein are associated with idiopathic dilated cardiomyopathy (DCM) and its progression.Methods and resultsWe screened 123 idiopathic DCM patients and 96 healthy individuals by single-strand conformation polymorphism analysis and direct sequencing for genetic variants in HRC. Six polymorphisms were detected: Leu35Leu (A/G), Ser43Asn (G/A), Ser96Ala (T/G), Glu202_Glu203insGlu (−/GAG), Asp261del (GAT/−), and an in-frame insertion of 51 amino acids at His321. The analysis of their frequencies did not reveal any significant correlation with DCM development. However, the Ser96Ala polymorphism exhibited a statistically significant correlation with the occurrence of life-threatening ventricular arrhythmias. During a follow-up of 4.02 ± 2.4 years, the risk for ventricular arrhythmias was higher (HR, 9.620; 95% CI, 2.183–42.394; P = 0.003) in the Ala/Ala patients, compared with Ser/Ser homozygous patients. On multivariable Cox regression analysis, the Ser96Ala polymorphism was the only significant genetic arrythmogenesis predictor in DCM patients (HR, 4.191; 95% CI, 0.838–20.967; P = 0.018).ConclusionThe Ser96Ala genetic variant of HRC is associated with life-threatening ventricular arrhythmias in idiopathic DCM and may serve as an independent predictor of susceptibility to arrhythmogenesis in the setting of DCM.

The tole of ischemic preconditioning in acute myocardial infarction

Ischemic preconditioning is a phenomenon in which brief episodes of ischemia and reperfusion increase myocardial tolerance and substantially reduce the infarction size. Two patients with acute left anterior descending artery occlusion received fibrinolytic therapy within 6 hours of symptom onset, but nevertheless developed myocardial infarctions of different size. The first patient, without a history of preinfarction angina, developed a large anterior infarction, because there was no time for ischemic preconditioning or development of coronary collateral vessels. The second patient, with a 4-day history of preinfarction angina, had a more favorable outcome - he developed apical necrosis, with greater myocardial viability in the infarct-related area. The beneficial effects of angina occurring 24-48h before infarction are resulting from ischemic preconditioning, which reduces cardiac mortality, infarct size and occurrence of life-threatening ventricular arrhythmias.

Noninvasive risk stratification in arrhythmogenic right ventricular cardiomyopathy.

The natural history of arrhythmogenic right ventricular cardiomyopathy is determined by the electrical instability of the dystrophic myocardium, which can precipitate arrhythmic cardiac arrest any time during the course of the disease and by the progressive myocardial loss that results in ventricular dysfunction and heart failure. Sudden death accounts for the majority of the fatal events but its occurrence is mostly unpredictable. There are no prospective and controlled studies assessing clinical markers that can predict the occurrence of life-threatening ventricular arrhythmias. However, the noninvasive risk profile, which emerges from retrospective analysis of clinical and pathologic series, is characterized by history of syncope, physical exercise, spontaneous ventricular tachycardia or ventricular fibrillation, right ventricular dysfunction, left ventricular involvement, right precordial negative T wave, right bundle branch block, QT-QRS dispersion, right precordial ST-segment elevation and late potentials. At present only QRS dispersion, history of syncope and right and/or left ventricular abnormalities at radionuclide angiography proved to be independent noninvasive predictors of sudden death.

Long-chain n-3 polyunsaturated fatty acids and out-of-hospital primary cardiac arrest: clinical and public health implications of observational studies and clinical trials*1

GISSI-Prevenzione findings provide additional support for the association of dietary intake of long-chain n-3 polyunsaturated fatty acids (PUFAs) from seafood [eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) with the risk of coronary heart disease (CHD) mortality and sudden cardiac death. The findings also complement evidence from animal-experimental studies, cell biology and dietary intervention trials that suggest that long-chain n-3 PUFAs may protect against the life-threatening ventricular arrhythmias that result in sudden cardiac death. In this report, we review (1) several issues initially raised in the interpretation of clinical epidemiological studies of the association of long-chain n-3 PUFAs and the risk of CHD and (2) findings from a population-based case-control study of dietary intake and cell-membrane levels of long-chain n-3 PUFAs from seafood and the risk of primary cardiac arrest, that complements the findings from the GISSI-Prevenzione trial. Taken together, the available data supports both the role of low-dose, long-chain n-3 PUFAs in the prevention of sudden cardiac death and further targeted clinical research to examine more fully the effects of lowdose, long-chain n-3 PUFAs on the occurrence of life-threatening ventricular arrhythmias in other clinically defined, high-risk populations.

Lipid lowering drugs and recurrences of life-threatening ventricular arrhythmias in high-risk patients

OBJECTIVESTo evaluate a possible effect of lipid lowering drugs on recurrences of ventricular arrhythmias (VA) after implantable cardioverter defibrillator (ICD) implantation.BACKGROUNDIn patients with coronary artery disease (CAD), lipid lowering drugs reduce total and sudden cardiac death. Because the mechanism is not completely understood, we studied whether these drugs have a favorable influence on the occurrence of life-threatening VA in patients with CAD and ICD implants.METHODSWe conducted an observational study in 78 patients with CAD and life-threatening VA, treated with an ICD. After ICD implantation, 27 patients were on treatment with lipid lowering drugs (group I) and 51 were not (group II). Patients were studied for the following end points: recurrences of VA requiring ICD intervention, cardiac death and hospitalization.RESULTSAfter a mean follow-up of 490 ± 319 days, 35 patients (45%) had recurrences of VA requiring ICD intervention. In multivariate analysis, the use of lipid lowering drugs (chi-square 6.33, p = 0.012) and poorly tolerated sustained monomorphic ventricular tachycardia as initial presentation (chi-square 4.84, p = 0.028) remained as independent predictors of recurrences of VA. Patients in groups I and II had similar baseline clinical characteristics, but patients in group I had a lower incidence of recurrences of VA (6/27 or 22% vs. 29/51 or 57%, p = 0.004) and of the combined end points of cardiac death and hospitalization (4/27 or 15% vs. 23/51 or 45%, p = 0.015) compared with patients in group II.CONCLUSIONSThis is the first observation that the use of lipid lowering drugs is associated with a reduction of recurrences of VA in patients with CAD and ICD implants. These data require confirmation in a prospective randomized trial.

Association of left ventricular remodeling and nonuniform electrical recovery expressed by nondipolar QRST integral map patterns in survivors of a first anterior myocardial infarction. Captopril and Thrombolysis Study Investigators.

Progressive left ventricular dilatation after myocardial infarction is associated with a high mortality rate, the majority of which is arrhythmogenic in origin. The underlying mechanism of this relation remains unknown. It has been suggested, however, that left ventricular dilatation is accompanied by changes in repolarization characteristics that may facilitate the occurrence of life-threatening ventricular arrhythmias. We examined 62-lead body surface QRST integral maps during sinus rhythm in 78 patients at 349 +/- 141 days after thrombolysis for a first anterior myocardial infarction. Visual map analysis was directed at discriminating dipolar (uniform repolarization) from nondipolar (nonuniform repolarization) patterns. In addition, the nondipolar content of each map was assessed quantitatively with the use of eigenvector analysis. Nondipolar map patterns were present in almost one third of the patients (32%). Left ventricular end-systolic and end-diastolic volumes were assessed echocardiographically before discharge and after 3 and 12 months with the use of the modified biplane Simpson rule. The increase in left ventricular end-systolic volume 1 year after myocardial infarction was more pronounced in patients with nondipolar QRST integral map patterns (14.47 +/- 14.10 versus 4.22 +/- 8.44 mL/m2, P = .017). In patients with an increase in end-systolic volume of more than 16 mL/m2 (upper quartile), the prevalence of nondipolar maps was 89% compared with 29% in patients with dilatation of less than 16 mL/m2. In addition, the nondipolar content of maps in patients in the upper quartile was significantly increased compared with the lower quartiles (49 +/- 14% versus 37 +/- 12%, P = .013). Logistic regression analysis revealed that an end-systolic volume of more than 42 mL/m2 after 1 year contributed independently to the appearance of nondipolar maps. Patients with high-grade ventricular arrhythmias showed a higher nondipolar content (49 +/- 17% versus 39 +/- 10%, P = .013). QTc dispersion did not discriminate between patients with and those without high-grade ventricular arrhythmias. Also, the association between left ventricular remodeling and nondipolar map patterns was confirmed prospectively in an additional group of 15 patients. Nondipolar map patterns are present in 32% of patients after thrombolysis for a first anterior myocardial infarction and are associated with increased left ventricular dilatation. These data support the hypothesis that left ventricular dilatation after myocardial infarction leads to changes in repolarization characteristics that may facilitate the occurrence of life-threatening ventricular arrhythmias.

Characteristics and prognosis of patients with acute myocardial infarction in relation to occurrence of congestive heart failure

Congestive heart failure is one of the major symptoms accompanying acute myocardial infarction (AMI). The study aimed to describe the occurrence, characteristics and prognosis of congestive heart failure in AMI and to compare post-MI patients with and without congestive heart failure. The methods used included baseline characteristics, initial symptoms, electrocardiogram (ECG), mortality during hospitalization and one year follow-up in consecutive patients with AMI admitted to Sahlgrenska Hospital, Göteborg, Sweden. Congestive heart failure was observed in 51% of the cases. Patients with congestive heart failure were older, more frequently had a history of previous cardiovascular disease, and, less frequently had chest pain on admission to hospital. They had a higher occurrence of life-threatening ventricular arrhythmias during initial hospitalization, and their mortality during one year follow-up was 39% as compared to 17% in patients without congestive heart failure (P < 0.001). This difference remained significant when correcting for differences at baseline. Patients with severe congestive heart failure had a one year mortality of 47% vs 31% in patients with moderate congestive heart failure (P < 0.01). Signs and symptoms of congestive heart failure occur in every second patient admitted to hospital due to AMI, and indicate a bad prognosis, which is directly related to the severity of congestive heart failure.