Arrhythmias In Heart Failure Patients Research Articles

The effects of empagliflozin on ventricular arrhythmias in heart failure patients with an implantable cardioverter-defibrillator: a double-blind randomized controlled trial.

Sodium-glucose transporter 2 (SGLT2) inhibitors such as empagliflozin are one of the main treatments for type 2 diabetes mellitus (DM2) and heart failure (HF). They have also demonstrated anti-arrhythmic effects in some preclinical and clinical studies. The purpose of this study was to assess the effects of empagliflozin on ventricular arrhythmias in HF patients with an implantable cardioverter-defibrillator (ICD). In a prospective double-blinded, randomized controlled trial of Iran County, Mashhad (72 patients 1:1), we compared the frequency and proportion of ventricular arrhythmias and ICD therapies during the 24weeks to the prior 24weeks. Results revealed that empagliflozin significantly reduced the frequency and proportion of ventricular tachycardia (VT)/fibrillation (VF) episodes (P = 0.019 and 0.039, respectively). Moreover, it tended to reduce the frequency and proportion of ICD therapies, including anti-tachycardia pacing (ATP) and shock. Subgroup analysis of patients with or without any antiarrhythmic drugs (digoxin, mexiletine, amiodarone, or sotalol) revealed that only patients who were previously on the antiarrhythmic drugs benefit from empagliflozin antiarrhythmic effects. In conclusion, empagliflozin exhibits anti-arrhythmic effects in HF patients with an ICD. Larger and long-term clinical studies are still needed to investigate and confirm all positive effects of SGLT2 inhibitors in this regard. Trial registration number: IRCT20120520009801N7 (Approval date: June 11, 2022).

Impact of Sacubitril/Valsartan Combination on Prevalence of Arrhythmia in Heart Failure Patients with Reduced Ejection Fraction

Abstract Aim and Objectives The aim of this study was to assess the effect of Sacubitril/Valsartan combination on prevalence of arrhythmias in HFrEF patients and compare it with patients on ACEI or ARBs only in addition to echo parameters follow up. Patients and Methods This study was conducted at Ain Shams university and Nasr city insurance hospitals and our target population was heart failure patients with reduced ejection fraction on either Sacubitril\Valsartan combination therapy (Group A) or on ACEI or ARBs (Group B) for at least 3 months, it was an observational study to follow up the burden of arrhythmia among heart failure patients by 48 hours holter monitoring at 3 and 6 months besides Echo parameters follow up. Results Our study included 2 groups. Group A (30 patients on Sacubitril/Valsartan combination therapy and mean age was 58.23 ± 4.80 years, 73.3% of patients were males and 26.7% females). Group B (30 patients on ACEIs or ARBs with mean age 56.37 ± 4.49 years, 80.0% of patients were males and 6 % females). There was no significant difference regarding the medical history, risk factors and NYHA classification of heart failure. The patients were classified into ischemic and non-ischemic cardiomyopathy patients and there was no significant difference between both groups. Group A was characterized by significant decrease in QTc values which reached the lowest values after 6 months, in the opposite side; group B was associated with increasing QTc values through the follow up period. As regards echocardiographic parameters we have found that left ventricle ejection fraction was improving to reach the highest values after six months in group A but we did not find significant improvement of left ventricle ejection fraction in group B. Other echocardiography parameters in group A including LA, LVIDd, RVSP and SWMA were improved by the end of the study but we have found that LA diameter was increasing in group B. In group A, burden of ventricular ectopics was found to be decreasing through the follow up period but there was no significant change of ventricular ectopics incidence in group B by the end of the study. Conclusion Sacubitril/Valsartan combination therapy was superior to ACEIs in reducing ventricular ectopics which means that this drug plays a role in preventing SCD. Ejection fraction in Sacubitril/Valsartan combination group was improving through the follow up period. Echocardiographic parameters were improving in Sacubitril/Valsartan group as regard LA, LVIDd and RVSP. Functional capacity in Sacubitril/Valsartan combinations group was improving through follow up period which means this drug reduces hospitalization.

Association of ivabradin use with ventricular arrhythmias in heart failure patients

Abstract Funding Acknowledgements Type of funding sources: None. Background/Introduction Heart failure patients with reduced left ventricular function are at high risk for ventricular arrhythmias and sudden cardiac death. Ivabradine, a specific inhibitor of the If current in the sinoatrial node, provides heart rate reduction in sinus rhythm and angina control in chronic coronary syndromes. Purpose The effect of ivabradine on ventricular arrhythmias in heart failure patients has not been fully elucidated. In this study, we aimed to investigate the effect of ivabradine use on life-threatening arrhythmias and long-term mortality in heart failure patients. Methods In this retrospective study, 1639 patients with heart failure were included. Patients were divided into two groups as ivabradine users and non-users. Patients presenting with ventricular tachycardia, presence of ventricular extra systole and ventricular tachycardia in 24-hour rhythm monitoring, appropriate ICD shocks and long-term mortality outcomes were evaluated according to ivabradine use. Results After adjustment for clinical variables, admission with ventricular tachycardia had 3.0 higher rates in ivabradine non-users (95% CI: 1.5 – 10.2). According to the adjusted model for all variables, approximately 4.1 times more appropriate ICD shocks were observed in the ivabradine non-users than the users (95% CI: 1.8 – 9.6). Long-term mortality did not differ between these groups after adjustment for all covariates. Conclusion The use of ivabradine reduced the appropriate ICD discharge in heart failure patients with low ejection fraction. Ivabradine has a potential in the treatment of ventricular arrhythmias in heart failure patients.

Effects of CRT on atrial and ventricular arrhythmias in patients with HF

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Cardiac resynchronization therapy (CRT) is an accepted treatment for patients with heart failure (HF). Cardiac arrhythmias present a significant and complex issue in this patient group. Evidence exploring the influence of CRT on cardiac arrhythmias rate variations is limited. Purpose Our research investigates the effectiveness of CRT in the treatment of existing and newly diagnosed atrial and ventricular arrhythmias, and impact of epicardial lead position on these arrhythmias rate variations, as well as on the CRT response. Methods This single-center, prospective, observational study included 75 consecutive patients admitted for CRT implantation over a 12-month period. All included patients had episodes of atrial and/or ventricular arrhythmias, diagnosed by 12-lead ECG or 24-hour Holter monitoring. Pre-procedural demographic characteristics were collected for all patients, including ECG records, NYHA functional class, echocardiographic assessment of left ventricular ejection function and questionnaire for quality-of-life. During device follow up atrial and ventricular arrhythmias appearance was monitored. Additional assessment of echocardiographic parameters, NYHA - functional class, quality of life and rate of major cardiovascular complications and rehospitalizations was performed. Results The mean age of the patients was 62.4 ± 10.3 years, with 74.6% male and 25.3% females. 72% had a non-ischemic HF etiology. Pre-procedural paroxysmal AF was present in 34.7%, persistent AF in 36%, PVCs in 32%, NSVT 16%, and VT in 18,7% patients. 55% of the included patients were responders to CRT. Our results showed decrease in rate of all ventricular arrhythmias, with significant reduction in the percentage of VT (p=0.003), regardless of CRT response. Significant reduction of PVCs and NSVT rate (p=0.012 & p=0.024) was found in the responder group of patients. Regarding AF, our results showed a decrease in the number of AF events in both patient groups, however this was most visible in the responder patients with paroxysmal AF (p=0.057). In CRT responders, left ventricular pacing lead was most commonly located in a lateral branch vein of the CS with middle and mid/lateral position. In terms of quality of life and general condition of the patients, we noticed a significant improvement in the NYHA - functional class (p <0.001), as well as in both parts of the quality-of-life assessment questionnaire (p=0.0135, p<0.001). Conclusion CRT is an effective treatment for atrial and ventricular arrhythmias in HF patients, especially in responders to this therapy. LV epicardial lead position proved to be very important influence in the process of LV reverse remodeling, which is in direct correlation of the CRT responders and its effectiveness in reducing the rate of cardiac arrhythmias.

Effect of ivabradine on ventricular arrhythmias in heart failure patients with reduced ejection fraction

Effect of ivabradine on ventricular arrhythmias in heart failure patients with reduced ejection fraction

Abstract 13743: Prevalence of Cardiac Rhythm Disturbances in Heart Failure Patients With and Without Cardiac Amyloidosis: A National Inpatient Sample Analysis

Background: Cardiac amyloidosis (CA) is well-known to affect electrocardiographic findings. However, the impact of CA on the prevalence of cardiac arrhythmias, particularly in heart failure (HF) patients, is unknown. Our aim was to assess the prevalence of arrhythmias in HF patients with and without CA. Methods: A retrospective cohort study was conducted using the Nationwide Inpatient Sample from 2017. About 5,074,059 patients who had acute, acute on chronic and chronic HF as primary or secondary diagnosis were identified and stratified based on the presence or absence of CA using ICD-10 codes. Both univariate regression and literature review were used to determine the covariates. Multivariate logistic regression analysis was used to adjust for confounders and analyze the variables. Results: Out of the 5,074,059 hospitalized patients with a primary and secondary diagnosis of HF, 7,980 individuals had CA. HF patients with CA had a higher prevalence of Atrial Fibrillation (AF) (52.6% vs 39.3%), Atrial Flutter (AFL) (9.4% vs 3.89%), Ventricular tachycardia (VT) (9.6% vs 4%), Supraventricular tachycardia (SVT) (3.9% vs 2.1%), right bundle branch block (RBBB) (2.9% vs 1.6%), 1st degree AV block (1AVB) (3.07% vs 1%), 2nd degree AV block (2AVB) (1.4% vs 0.4%), and 3rd degree AV block (3AVB) (1.25% vs 0.7%) than without. When adjusted to patient demographics, comorbidities, and hospital characteristics, HF patients with CA had higher risk of AF (aOR= 1.67, p<0.0001), AFL (aOR=2.9, p<0.0001), VT (aOR=2.08, p<0.0001), SVT (aOR=1.63, p<0.0001), RBBB (aOR=1.62, p=0.002), 1AVB (aOR=2.27, p<0.0001), and 2AVB (aOR=2.86, p<0.0001) compared to those without. However, there was no significant difference in the prevalence of Ventricular Fibrillation (VF) (aOR=0.92, p=0.82) in the same population. Conclusion: HF patients with CA are 67%, 190%, 108%, 63%, 62%, 127%, and 186% more likely to develop AF, AFL, VT, SVT, RBBB, 1AVB, and 2AVB respectively, than those without. However, HF patients with CA did not have a significant difference in the prevalence of VF, 3AVB, and LBBB. CA is an infiltrative disease process that is known to cause cardiac conduction disturbances. Limitations include the underdiagnosis of CA in our society as well as the non-specificity of ICD codes for CA.

Fragmented QRS is associated with ventricular arrhythmias in heart failure patients: A systematic review and meta-analysis.

IntroductionMany primary prevention heart failure (HF) patients with an implantable cardiac defibrillator (ICD) rarely experience life‐threatening ventricular arrhythmias (VA). New strategies are required to identify patients most at risk of VA and sudden cardiac death who would benefit from an ICD. One potential method is the detection of fragmented QRS (fQRS) on the electrocardiogram. The aim was to assess the predictive capacity of fQRS for VA and mortality in ischemic (ICM) and non‐ischemic cardiomyopathy (NICM) primary prevention HF patients.Methods and ResultsA systematic review and meta‐analysis of studies examining fQRS in HF patients with or without an ICD who met primary prevention indications with reduced ejection fraction ≤40%. Outcome measures were VA (or appropriate ICD therapy) and all‐cause mortality. Ten studies involving 3885 patients were included for analysis. Most patients were male with non‐fQRS patients being significantly younger (−1.5[−2.66, −0.42], p = .03). Diabetes was more likely in fQRS patients (1.12[1.01, 1.25], p = .03) while non‐fQRS patients were 28% more likely to have a history of atrial fibrillation (0.82[0.67,1.00], p = .05). Ventricular arrhythmias were significantly 1.5 times more likely in patients with fQRS (1.51[1.02, 2.25], p = .04). HF patients were 1.7 times more likely to die of any cause if fQRS was present (1.68[1.13, 2.52], p = .01). NICM patients with fQRS have a significant 2.6‐fold increased incidence of death compared with ICM patients (2.55[1.63, 3.98], p < .0001).ConclusionfQRS is associated with VA and all‐cause mortality and may be a novel marker in the risk stratification of primary prevention HF patients indicated for ICD implantation.

Remodeling of the Purkinje Network in Congestive Heart Failure in the Rabbit.

Purkinje fibers (PFs) control timing of ventricular conduction and play a key role in arrhythmogenesis in heart failure (HF) patients. We investigated the effects of HF on PFs. Echocardiography, electrocardiography, micro-computed tomography, quantitative polymerase chain reaction, immunohistochemistry, volume electron microscopy, and sharp microelectrode electrophysiology were used. Congestive HF was induced in rabbits by left ventricular volume- and pressure-overload producing left ventricular hypertrophy, diminished fractional shortening and ejection fraction, and increased left ventricular dimensions. HF baseline QRS and corrected QT interval were prolonged by 17% and 21% (mean±SEMs: 303±6 ms HF, 249±11 ms control; n=8/7; P=0.0002), suggesting PF dysfunction and impaired ventricular repolarization. Micro-computed tomography imaging showed increased free-running left PF network volume and length in HF. mRNA levels for 40 ion channels, Ca2+-handling proteins, connexins, and proinflammatory and fibrosis markers were assessed: 50% and 35% were dysregulated in left and right PFs respectively, whereas only 12.5% and 7.5% changed in left and right ventricular muscle. Funny channels, Ca2+-channels, and K+-channels were significantly reduced in left PFs. Microelectrode recordings from left PFs revealed more negative resting membrane potential, reduced action potential upstroke velocity, prolonged duration (action potential duration at 90% repolarization: 378±24 ms HF, 249±5 ms control; n=23/38; P<0.0001), and arrhythmic events in HF. Similar electrical remodeling was seen at the left PF-ventricular junction. In the failing left ventricle, upstroke velocity and amplitude were increased, but action potential duration at 90% repolarization was unaffected. Severe volume- followed by pressure-overload causes rapidly progressing HF with extensive remodeling of PFs. The PF network is central to both arrhythmogenesis and contractile dysfunction and the pathological remodeling may increase the risk of fatal arrhythmias in HF patients.

Ventricular arrhythmia in heart failure patients with reduced ejection fraction and central sleep apnoea.

Cheyne–Stokes respiration (CSR) may trigger ventricular arrhythmia in patients with heart failure with reduced ejection fraction (HFrEF) and central sleep apnoea (CSA). This study determined the prevalence and predictors of a high nocturnal ventricular arrhythmia burden in patients with HFrEF and CSA (with and without CSR) and to evaluate the temporal association between CSR and the ventricular arrhythmia burden. This cross-sectional ancillary analysis included 239 participants from the SERVE-HF major sub-study who had HFrEF and CSA, and nocturnal ECG from polysomnography. CSR was stratified in ≥20% and <20% of total recording time (TRT). High burden of ventricular arrhythmia was defined as >30 premature ventricular complexes (PVCs) per hour of TRT. A sub-analysis was performed to evaluate the temporal association between CSR and ventricular arrhythmias in sleep stage N2. High ventricular arrhythmia burden was observed in 44% of patients. In multivariate logistic regression analysis, male sex, lower systolic blood pressure, non-use of antiarrhythmic medication and CSR ≥20% were significantly associated with PVCs >30·h−1 (OR 5.49, 95% CI 1.51–19.91, p=0.010; OR 0.98, 95% CI 0.97–1.00, p=0.017; OR 5.02, 95% CI 1.51–19.91, p=0.001; and OR 2.22, 95% CI 1.22–4.05, p=0.009; respectively). PVCs occurred more frequently during sleep phases with versus without CSR (median (interquartile range): 64.6 (24.8–145.7) versus 34.6 (4.8–75.2)·h−1 N2 sleep; p=0.006). Further mechanistic studies and arrhythmia analysis of major randomised trials evaluating the effect of treating CSR on ventricular arrhythmia burden and arrhythmia-related outcomes are warranted to understand how these data match with the results of the parent SERVE-HF study.

P1407Efficacy of radiofrequency ablation of paroxysmal and persistent atrial fibrillation in heart failure patients

Abstract Background radiofrequency ablation (RFA) is considered to be one of the most preferred treatments for atrial fibrillation (AFib) in patients with heart failure (HF). Objective to study the effectiveness of AFib RFA in patients with HF, to compare the effectiveness of the procedure in patients with paroxysmal (PaAFib) and persistent (PeAFib) AFib. Materials and methods 65 patients with AF and HF with LVEF &amp;lt; 50%, who underwent RFA were included in a prospective study. All patients underwent transthoracic echocardiography and quality of life assessment using the SF-36 questionnaire before RFA and after 12 months. AFib was recorded in 42 (65%) of patients, AFL in 23 (35%). Thirty (46%) patients had PaAfib (Group 1), and 35 (54%) PeAFib (Group 2). Results In 45 (69%) patients sinus rhythm (SR) was restored during RFA, in 15 (23%) SR was restored by electrical cardioversion. In 5 (8%) patients with PaAFib revealed SR at the time of RFA. Twelve month follow-up period revealed 49 (75%) patients who were free from AFib: 23 (77%) patients with PaAFib and 26 (74%) with PeAFib. After 12 month follow-up we revealed the improvement in LVEF (p &amp;lt; 0.001 in both groups), decrease of anteroposterior size of left atrium (LA) (p &amp;lt; 0.001 in both groups) and LA volume (p &amp;lt; 0.001 in both groups), improvement in the mental (p = 0.008 in Group 1; p = 0.006 in Group 2) and physical component of health according to the SF-36 questionnaire (p = 0.036 in Group 1; p = 0.049 in Group 2). There were no significant differences between two groups of follow-up period. Conclusions AFib RFA significantly improves the course of heart failure and the quality of life of patients, leads to decrease of left atrium size and increase of LVEF. The effectiveness of RFA does not depend on the type of arrhythmia in HF patients.

Evaluating the Therapeutic Efficacy and Safety of Landiolol Hydrochloride for Management of Arrhythmia in Critical Settings: Review of the Literature.

BackgroundLandiolol hydrochloride, a highly cardio-selective beta-1 blocker with an ultra-short-acting half-life of 4 minutes, was originally approved by Japan for treatment of intraoperative tachyarrhythmias. This review aims to provide an integrated overview of the current state of knowledge of landiolol hydrochloride in the management of arrhythmia in critical settings.MethodsWe searched MEDLINE, EMBASE, and the Cochrane Library to retrieve relevant articles with a total of 65 records identified.ResultsThe high β1 selectivity (β1/β2 ratio of 255:1) of landiolol causes a more rapid heart rate (HR) decrease compared to esmolol while avoiding decreases in mean arterial blood pressure. Recently, it has been found useful in left ventricular dysfunction patients and fatal arrhythmia requiring emergency treatment. Recent random clinical trials (RCT) have revealed therapeutic and prophylactic effects on arrhythmia, and very low-dose landiolol might be effective for preventing postoperative atrial fibrillation (POAF) and sinus tachycardia. Likewise, landiolol is an optimal choice for perioperative tachycardia treatment during cardiac surgery. The high β1 selectivity of landiolol is useful in heart failure patients as a first-line therapy for tachycardia and arrhythmia as it avoids the typical depression of cardiac function seen in other β-blockers. Application in cardiac injury after percutaneous coronary intervention (PCI), protection for vital organs (lung, kidney, etc.) during sepsis, and stabilizing hemodynamics in pediatric patients are becoming the new frontier of landiolol use.ConclusionLandiolol is useful as a first-line therapy for the prevention of POAF after cardiac/non-cardiac surgery, fatal arrhythmias in heart failure patients and during PCI. Moreover, the potential therapeutic effect of landiolol for sepsis in pediatric patients is currently being explored. As positive RCT results continue to be published, new clinical uses and further clinical studies in various settings by cardiologists, intensivists and pediatric cardiologists are being conducted.

P3106Atrial fibrillation is not associated with the responses to exercise training in heart failure patients with preserved ejection fraction

Abstract Background Atrial fibrillation (AF) is known as a common arrhythmia in heart failure patients with preserved left ventricular ejection fraction (HFpEF). Several studies have reported that HFpEF patients with AF show lower exercise tolerance and poorer prognosis as compared with those with sinus rhythm (SR). On the other hand, exercise training is documented to improve peripheral muscle function and exercise tolerance in HFpEF patients. However, the relationship between AF status and outcomes due to exercise training is still unclear in these patients. Purpose We aimed to investigate the influence of AF on the responses to outcomes with exercise training in HFpEF patients. Methods We studied 426 patients with HFpEF who received 5-month cardiac rehabilitation including exercise training during hospitalization and after hospital discharge. As clinical characteristics, we obtained body mass index, disease aetiology, comorbidity conditions, blood examination and echocardiographic variables from medical records. We also measured isometric quadriceps strength (QS) and 6-minute walk distance (6MWD) as peripheral muscle strength and exercise tolerance, respectively. The QS and 6MWD were assessed at hospital discharge as the baseline and 5 months later. AF status was determined by the presence on electrocardiogram at baseline 6MWD or medical history of AF during hospitalization. In statistical analysis, we compared baseline clinical characteristics, QS and 6MWD between the rhythm status (SR group or AF group). We also examined the changes in QS and 6MWD from baseline to the 5-month observation period (ΔQS and Δ6MWD) and compared them between the 2 groups using analysis of covariance with adjustment for baseline clinical confounding factors. Results At baseline, 289 patients (68%) were in SR, and 111 patients (26%) had AF. The AF was associated significantly with older age (P&lt;0.001) and lower levels of estimated glomerular filtration rate (P=0.013), QS (P&lt;0.001) and 6MWD (P&lt;0.001) at baseline. The QS increased significantly from 25.2±11.0 kg at baseline to 30.8±13.0 kg after 5-month cardiac rehabilitation in the SR group, and from 21.1±8.3 kg to 26.0±9.4 kg in the AF group (P&lt;0.001, respectively). The 6MWD also increased significantly from 394.8±129.2 to 463.5±133.5 meters in the SR, and from 343.7±107.9 to 403.0±114.5 meters in the AF (P&lt;0.001, respectively). There were no significant differences in ΔQS and Δ6MWD between the SR and AF groups even after adjustment for clinical confounding factors including baseline QS or 6MWD (Figure). Conclusions The AF status in HFpEF patients was associated with older age, lower peripheral muscle function and also lower exercise tolerance at baseline, but not associated with the responses to exercise training. Acknowledgement/Funding JSPS KAKENHI JP16K16442

Non-Invasive Detection of Mechanical Alternans Utilizing Photoplethysmography.

Mechanical alternans (MA) is a biomarker associated with mortality and life-threatening arrhythmias in heart failure patients. Despite showing prognostic value, its use is limited by the requirement of measuring the continuous blood pressure (BP), which is costly and impractical. To develop and test, for the first time, non-invasive MA surrogates based on photoplethysmography (PPG). Continuous BP and PPG were recorded during clinical procedures and tests in 35 patients. MA was induced either by ventricular pacing (Group A, N = 19) or exercise (Group B, N = 16). MA was categorized as sustained or intermittent if MA episodes were observed in at least 20 or between 12 and 20 consecutive beats, respectively. Eight features characterizing the pulse morphology were derived from the PPG, and MA surrogates were evaluated. Sustained alternans was observed in 9 patients (47%) from Group A, whereas intermittent alternans was observed in 13 patients (68%) from Group A and in 10 patients (63%) from Group B. The PPG-based MA surrogate showing the highest accuracy, V'M, was based on the maximum of the first derivative of the PPG pulse. It detected both sustained and intermittent MA with 100% sensitivity and 100% specificity in Group A and intermittent MA with 100% sensitivity and 83% specificity in Group B. Furthermore, the magnitudes of MA and its PPG-based surrogate were linearly correlated (R2 = 0.83, p < 0.001). MA can be accurately identified non-invasively through PPG analysis. This may have important clinical implications for risk stratification and remote monitoring.

SY1-1 - Pharmacologic Management of Arrhythmia in Heart Failure

Arrhythmia confers a substantial risk of mortality and morbidity in patients with heart failure (HF). The treatment goals of arrhythmia in HF patients are to improve prognosis and quality of life. Sudden cardiac death (SCD), which is primarily caused by ventricular tachycardia (VT)/fibrillation (VF), accounts for approximately one-third of all deaths in HF patients. Implantable cardioverter-defibrillator (ICD) is useful for preventing SCD, but the improvement of outcome is limited in patients with advanced HF. Beta-blockers reduces SCD and improves survival. Amiodarone is potentially effective to prevent VT/VF. Intravenous nifekalant, a pure class III antiarrhythmic drug, or intravenous amiodarone is useful in the emergency treatment of VT/VF. Recently, short-acting intravenous beta-blocker such as landiolol can be tried. Atrial fibrillation (AF) frequently occurs in HF patients and leads to clinical and hemodynamic deterioration. They also increase a risk of HF deterioration. Amiodarone is safely used in HF patients. In AF patients with congestive, landiolol can also be used to control the ventricular rate as an intravenous infusion. In conclusions, standard pharmacologic therapy for HF including beta-blockers should be optimized to prevent arrhythmia as well as mortality. In emergency and acute care settings, short-acting beta-blocker may have an important role in management of arrhythmia and HF.

Analysis of 24-h Rhythm in Ventricular Repolarization Identifies QT Diurnality As a Novel Clinical Parameter Associated with Previous Ventricular Arrhythmias in Heart Failure Patients.

Introduction: Cardiac repolarization abnormalities are among the major causes of ventricular arrhythmias and sudden cardiac death. In humans, cardiac repolarization duration has a 24-h rhythm. Animal studies show that this rhythm is regulated by 24-h rhythms in ion channel function and that disruption of this rhythm leads to ventricular arrhythmias. We hypothesized that 24-h rhythms in QT duration can be used as a predictor for sudden cardiac death and are associated with ventricular arrhythmias. Secondly, we assessed a possible mechanistic explanation by studying the putative role of hERG channel dysfunction.Materials and Methods: In 2 retrospective studies, measures of the 24-h variation in the QT and QTc intervals (QT and QTc diurnality, QTd and QTcd, respectively) have been derived from Holter analyses and compared between groups: 1) 39 post-infarct patients with systolic heart failure (CHF: EF < 35%), of which 14 with, and 25 without a history of ventricular arrhythmias and 2) five patients with proven (LQTS2) and 16 with potential (Sotalol-induced) hERG channel dysfunction vs. 22 controls.Results: QTd was two-fold higher in CHF patients with a history of ventricular arrhythmias (38 ± 15 ms) compared to CHF patients without VT (16 ± 9 ms, p = 0.001). QTd was significantly increased in LQT2 patients (43 ± 24 ms) or those treated with Sotalol (30 ± 10 ms) compared to controls (21 ± 8 ms, p < 0.05 for both).Discussion: QT diurnality presents a novel clinical parameter of repolarization that can be derived from Holter registrations and may be useful for identification of patients at risk for ventricular arrhythmias.

Autonomic Modulation in Patients with Heart Failure Increases Beat-to-Beat Variability of Ventricular Action Potential Duration.

Background: Exaggerated beat-to-beat variability of ventricular action potential duration (APD) is linked to arrhythmogenesis. Sympathetic stimulation has been shown to increase QT interval variability, but its effect on ventricular APD in humans has not been determined.Methods and Results: Eleven heart failure patients with implanted bi-ventricular pacing devices had activation–recovery intervals (ARI, surrogate for APD) recorded from LV epicardial electrodes under constant RV pacing. Sympathetic activity was increased using a standard autonomic challenge (Valsalva) and baroreceptor indices were applied to determine changes in sympathetic stimulation. Two Valsalvas were performed for each study and were repeated, both off and on bisoprolol. In addition sympathetic nerve activity (SNA) was measured from skin electrodes on the thorax using a novel validated method. Autonomic modulation significantly increased mean short-term variability in ARI; off bisoprolol mean STV increased from 3.73 ± 1.3 to 5.27 ± 1.04 ms (p = 0.01), on bisoprolol mean STV of ARI increased from 4.15 ± 1.14 to 4.62 ± 1 ms (p = 0.14). Adrenergic indices of the Valsalva demonstrated significantly reduced beta-adrenergic function when on bisoprolol (Δ pressure recovery time, p = 0.04; Δ systolic overshoot in Phase IV, p = 0.05). Corresponding increases in SNA from rest both off (1.4 uV, p < 0.01) and on (0.7 uV, p < 0.01) bisoprolol were also seen.Conclusions: Beat-to-beat variability of ventricular APD increases during brief periods of increased sympathetic activity in patients with heart failure. Bisoprolol reduces, but does not eliminate, these effects. This may be important in the genesis of ventricular arrhythmias in heart failure patients.

Electrical treatment of atrial arrhythmias in heart failure patients implanted with a dual defibrillator CRT device. Results from the TRADE-HF study

BackgroundVentricular and atrial arrhythmias commonly occur in heart failure patients and are a significant source of symptoms, morbidity and mortality. Some specific generators referred to as dual defibrillators, Dual CRT-Ds, have the ability to treat atrial and ventricular arrhythmias. TRADE-HF is a prospective two-arm randomized study aimed at assessing the benefits of complete automatic management of atrial arrhythmias in patients implanted with a dual CRT-D. MethodsPrimary objective of the TRADE-HF study was to document reduction of unplanned hospital admission for cardiac reasons or death for cardiovascular causes or progression to permanent AF, by comparing fully-automatic device driven therapy for atrial tachycardia or fibrillation (AT/AF) to an in-hospital approach for treatment of symptomatic AT/AF. Randomized Patients were followed every 6months for 3years to assess the primary objective. ResultsFour-hundred-twenty patients have been enrolled in the study. At the end of the study 30 subjects died for cardiovascular causes, 60 had at least one hospitalization for cardiovascular causes and 14 developed permanent AF. Eighty-seven patients experienced a composite event. Hazard Ratio for device-managed automatic therapy arm compared to traditional was 0.987 (95% CI: 0.684–1.503; p=0.951). The primary endpoint analysis resulted in no difference between the device managed and in-hospital treatment arm. ConclusionThe TRADE-HF study failed to demonstrate a reduction in the composite of unplanned hospitalizations for cardiovascular causes or death for cardiovascular causes or progression to permanent AF using automatic atrial therapy compared to a traditional approach including hospitalization for symptomatic episodes and/or in-hospital treatment of AT/AF.

The effect of long-term amiodarone administration on myocardial fibrosis and evolution of left ventricular remodeling in a porcine model of ischemic cardiomyopathy.

Amiodarone is effective in suppressing arrhythmias in heart failure patients. We investigated the effect of long-term amiodarone administration on myocardial fibrosis and left ventricular (LV) remodeling in a porcine model of ischemic cardiomyopathy. Eighteen infarcted farm pigs were randomized to receive long-term amiodarone administration for 3 months (n = 9) or conventional follow-up (n = 9). Evolution of LV remodeling over 3 months post-myocardial infarction was examined at tissue level (myocyte size, myocardial fibrosis and vascular density assessed by whole-field digital histopathology), organ level (LV structure and function assessed by echocardiography), and systemic level (BNP and MMP-9 levels). Long-term administration of the standard anti-arrhythmic doses of amiodarone was not associated with adverse effects on myocardial fibrosis and other features of adverse cardiac remodeling. This favorable safety profile suggests that long-term anti-arrhythmic therapy with amiodarone warrants further clinical investigation in the subpopulation of heart failure patients with significantly increased burden of arrhythmias.

Aerobic interval training reduces inducible ventricular arrhythmias in diabetic mice after myocardial infarction.

Diabetes mellitus (DM) increases the risk of heart failure after myocardial infarction (MI), and aggravates ventricular arrhythmias in heart failure patients. Although exercise training improves cardiac function in heart failure, it is still unclear how it benefits the diabetic heart after MI. To study the effects of aerobic interval training on cardiac function, susceptibility to inducible ventricular arrhythmias and cardiomyocyte calcium handling in DM mice after MI (DM-MI). Male type 2 DM mice (C57BLKS/J Lepr (db) /Lepr (db) ) underwent MI or sham surgery. One group of DM-MI mice was submitted to aerobic interval training running sessions during 6 weeks. Cardiac function and structure were assessed by echocardiography and magnetic resonance imaging, respectively. Ventricular arrhythmias were induced by high-frequency cardiac pacing in vivo. Protein expression was measured by Western blot. DM-MI mice displayed increased susceptibility for inducible ventricular arrhythmias and impaired diastolic function when compared to wild type-MI, which was associated with disruption of cardiomyocyte calcium handling and increased calcium leak from the sarcoplasmic reticulum. High-intensity exercise recovered cardiomyocyte function in vitro, reduced sarcoplasmic reticulum diastolic calcium leak and significantly reduced the incidence of inducible ventricular arrhythmias in vivo in DM-MI mice. Exercise training also normalized the expression profile of key proteins involved in cardiomyocyte calcium handling, suggesting a potential molecular mechanism for the benefits of exercise in DM-MI mice. High-intensity aerobic exercise training recovers cardiomyocyte function and reduces inducible ventricular arrhythmias in infarcted diabetic mice.

Molecular imaging to predict ventricular arrhythmia in heart failure

Ventricular tachycardia (VT) is a major cause of sudden cardiac death (SCD) in patients with heart failure (HF). Left ventricular ejection fraction (LVEF) and heart failure class according to the New York Heart association (NYHA) are in most common use to identify patients that may benefit from implantable cardioverter defibrillator (ICD) therapy. But during 3 years of follow up only 35% of patients receive appropriate ICD action. Therefore, there is a continued need for refinement of selection criteria for ICD implantation. In this regard, molecular imaging of the autonomic nervous system, which plays a central role in HF progression and cardiac electro-mechanical regulation, can make a substantial contribution. This article reviews the currently available literature concerning the value of molecular neuronal cardiac imaging for prediction of ventricular arrhythmias in HF patients.