Upgrade of right ventricular pacing to cardiac resynchronization therapy in heart failure: a randomized trial.

BACKGROUND AND AIMS: De novo implanted cardiac resynchronization therapy with defibrillator (CRT-D) reduces the risk of morbidity and mortality in patients with left bundle branch block, heart failure and reduced ejection fraction (HFrEF). However, among HFrEF patients with right ventricular pacing (RVP), the efficacy of CRT-D upgrade is uncertain. METHODS: In this multicentre, randomized, controlled trial, 360 symptomatic (New York Heart Association Classes II-IVa) HFrEF patients with a pacemaker or implantable cardioverter defibrillator (ICD), high RVP burden ≥ 20%, and a wide paced QRS complex duration ≥ 150 ms were randomly assigned to receive CRT-D upgrade (n = 215) or ICD (n = 145) in a 3:2 ratio. The primary outcome was the composite of all-cause mortality, heart failure hospitalization, or <15% reduction of left ventricular end-systolic volume assessed at 12 months. Secondary outcomes included all-cause mortality or heart failure hospitalization. RESULTS: Over a median follow-up of 12.4 months, the primary outcome occurred in 58/179 (32.4%) in the CRT-D arm vs. 101/128 (78.9%) in the ICD arm (odds ratio 0.11; 95% confidence interval 0.06-0.19; P < .001). All-cause mortality or heart failure hospitalization occurred in 22/215 (10%) in the CRT-D arm vs. 46/145 (32%) in the ICD arm (hazard ratio 0.27; 95% confidence interval 0.16-0.47; P < .001). The incidence of procedure- or device-related complications was similar between the two arms [CRT-D group 25/211 (12.3%) vs. ICD group 11/142 (7.8%)]. CONCLUSIONS: In pacemaker or ICD patients with significant RVP burden and reduced ejection fraction, upgrade to CRT-D compared with ICD therapy reduced the combined risk of all-cause mortality, heart failure hospitalization, or absence of reverse remodelling.

Prevalence of Lyme Carditis in Patients with Atrioventricular Blocks.

Infections with Borrelia may cause cardiac conduction system abnormalities, including atrioventricular blocks (AVBs). Therefore, we aimed to identify patients in whom Lyme carditis (LC) could be considered as the initial diagnosis among consecutive subjects who were referred for implantation of a permanent pacemaker due to symptomatic AVBs. To date, such a systematic evaluation has not been reported yet. Validation of the Suspicious Index for Lyme Carditis (SILC) in our study population was considered as an additional goal. We investigated consecutive patients with AVB admitted to our department for a pacemaker implantation. Serological diagnostic tests against Borrelia burgdorferi sensu lato (Bbsl) were performed in those with no obvious cardiac causes of AVB. The final study population consisted of 130 patients (80 M, mean age 67.4 ± 17.6). Lyme carditis was assumed as the initial diagnosis in 16 patients (12%) based on ABV and IgM Bbsl seropositivity. The patients with LC were younger and more frequently manifested constitutional symptoms of infection and fluctuating AVB. The highest prognostic value for identification of LC patients was obtained for the modified SILC, which included the following parameters: (1) age lower than 75 years; (2) risky outdoor activity and living in the countryside; (3) tick bite; (4) constitutional symptoms of Lyme disease; (5) erythema migrans; (6) male sex and (7) fluctuating atrioventricular block. We concluded that diagnostics for LC should be routinely considered in patients with advanced AVB. Modified SILC may identify the patients at risk of LC.

Baseline clinical characteristics of heart failure patients with reduced ejection fraction enrolled in the BUDAPEST-CRT Upgrade trial.

AIMS: The BUDAPEST-CRT Upgrade study is the first prospective, randomized, multicentre clinical trial investigating the outcomes after cardiac resynchronization therapy (CRT) upgrade in heart failure (HF) patients with intermittent or permanent right ventricular (RV) pacing with wide paced QRS. This report describes the baseline clinical characteristics of the enrolled patients and compares them to cohorts from previous milestone CRT studies. METHODS AND RESULTS: This international multicentre randomized controlled trial investigates 360 patients having a pacemaker (PM) or implantable cardioverter defibrillator (ICD) device for at least 6 months prior to enrolment, reduced left ventricular ejection fraction (LVEF ≤35%), HF symptoms (New York Heart Association [NYHA] functional class II-IVa), wide paced QRS (>150 ms), and ≥20% of RV pacing burden without having a native left bundle branch block. At enrolment, the mean age of the patients was 73 ± 8 years; 89% were male, 97% were in NYHA class II/III functional class, and 56% had atrial fibrillation. Enrolled patients predominantly had conventional PM devices, with a mean RV pacing burden of 86%. Thus, this is a patient cohort with advanced HF, low baseline LVEF (25 ± 7%), high N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (2231 pg/ml [25th-75th percentile 1254-4309 pg/ml]), and frequent HF hospitalizations during the preceding 12 months (50%). CONCLUSION: When compared with prior CRT trial cohorts, the BUDAPEST-CRT Upgrade study includes older patients with a strong male predominance and a high burden of atrial fibrillation and other comorbidities. Moreover, this cohort represents an advanced HF population with low LVEF, high NT-proBNP, and frequent previous HF events. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT02270840.

The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure: a multinational randomized trial.

The sodium-glucose cotransporter 2 inhibitor empagliflozin reduces the risk of cardiovascular death or heart failure hospitalization in patients with chronic heart failure, but whether empagliflozin also improves clinical outcomes when initiated in patients who are hospitalized for acute heart failure is unknown. In this double-blind trial (EMPULSE; NCT04157751 ), 530 patients with a primary diagnosis of acute de novo or decompensated chronic heart failure regardless of left ventricular ejection fraction were randomly assigned to receive empagliflozin 10 mg once daily or placebo. Patients were randomized in-hospital when clinically stable (median time from hospital admission to randomization, 3 days) and were treated for up to 90 days. The primary outcome of the trial was clinical benefit, defined as a hierarchical composite of death from any cause, number of heart failure events and time to first heart failure event, or a 5 point or greater difference in change from baseline in the Kansas City Cardiomyopathy Questionnaire Total Symptom Score at 90 days, as assessed using a win ratio. More patients treated with empagliflozin had clinical benefit compared with placebo (stratified win ratio, 1.36; 95% confidence interval, 1.09-1.68; P = 0.0054), meeting the primary endpoint. Clinical benefit was observed for both acute de novo and decompensated chronic heart failure and was observed regardless of ejection fraction or the presence or absence of diabetes. Empagliflozin was well tolerated; serious adverse events were reported in 32.3% and 43.6% of the empagliflozin- and placebo-treated patients, respectively. These findings indicate that initiation of empagliflozin in patients hospitalized for acute heart failure is well tolerated and results in significant clinical benefit in the 90 days after starting treatment.

The safety, efficacy, and cost-effectiveness of gentamycin-collagen sponge in multicomponent prevention strategy of cardiac implantable electronic device infections - a single-center experience.

BACKGROUND: Cardiac implantable electronic device(CIED)infections are associated with significant morbidity, mortality, and increased healthcare expenses. Apart from standard systemic antibiotic therapy, locally acting agents are under investigation as a potential approach for the prevention of this complication. AIMS: The study aimed to summarize our experience with a gentamycin-collagen sponge (GCS) in a multi-component prevention strategy of cardiac implantable electronic device infection. METHODS: We retrospectively analyzed medical records of 312 consecutive patients who underwent CIED-related surgery and had at least a 6-month follow-up. All the individuals had GCS applied during surgery. An incidence of CIEDs-related infection in our group was compared to the risk level calculated according to the commonly used scores. Analysis of cost-effectiveness was also performed. RESULTS: Incidence of CIED-related infection, defined as a primary endpoint, occurred relatively rarely (0.33%) as compared to the infection risk calculated according to commonly used scores Prevention of Arrythmia Device Infection Trial (PADIT) - 0.83%; CIED-AI - 0.90% or Mittal score - 1.00%; P<0.001 - for all). We did not record any complications related to GCS. We analyzed the cost-effectiveness of our GCS-based approach, which appeared to be financially beneficial (number needed to treat 149-200; difference of CIED infection treatment cost and GCSs price was 5093-26525 $). CONCLUSIONS: We conclude that: (1) the use of GCS to reduce CIEDs infections is feasible and safe; (2) our multicomponent prevention strategy involving the GCS application seems to significantly reduce the rate of CIED infection, and it is cost-effective.

New Polish prototypes of 4- and 8-mm-tip nonirrigated radiofrequency ablation catheters: an in vitro study.

BACKGROUND: Effectiveness of lesion formation during radiofrequency (RF) catheter ablation can be assessed using in vitro or in vivo animal models. AIMS: In this in vitro study, we aimed to compare the prototypes of the first Polish RF ablation catheters with common commercially available catheters from other manufacturers. METHODS: Samples of the porcine left ventricle were subject to temperature-controlled ablation (50 W / 50 oC / 60 s), using 4- and 8-mm -tip nonirrigated ablation catheters (commercial ones as well as new prototypes). The parameters of RF delivery were collected during energy applications. Subsequently, lesion dimensions were measured and compared between catheters. RESULTS: Initial impedance and impedance drop during energy delivery differed significantly between catheters (both those with 4-mm and 8-mm tip electrodes). The maximum temperature was similar for 4-mm -tip catheters (P = 0.26), while it differed for 8-mm -tip ones (P <0.001). No significant differences between catheters were noted for lesion volume. The 8-mm -tip prototypes created lesions of greater depth (mean [SD], 5.8 [0.4] mm vs 4.7 [0.4] mm; P <0.001) and volume (mean [interquartile range], 239.4 [217.9-255.5] mm3 vs 173.7 [156.1-186.4] mm3; P <0.001) than those with a 4-mm tip electrode. CONCLUSIONS: Our study showed that RF ablation catheters with the same length of the tip electrode created lesions of similar volume, irrespective of the manufacturer and despite showing distinct physical parameters during energy applications. The Polish catheter prototypes showed similar performance as commercially available devices. Finally, 8-mm -tip prototypes produced lesions of greater depth and volume than those with a 4-mm tip electrode.

Multicentre early experience with totally subcutaneous cardioverter-defibrillators in Poland.

INTRODUCTION: Implantable cardioverter-defibrillators (ICD) have a strong position in the prevention of sudden death. Nowadays, the most commonly used high-energy cardiac devices are transvenous ICDs. A new technology of totally subcutaneous ICDs (S-ICD) was invented and recently introduced into clinical practice in order to reduce lead-related complications of conventional ICDs. The aim of this paper is to present early experience with this new technology implemented in a few centres in Poland. MATERIAL AND METHODS: Medical records of patients who had S-ICD-related interventions in Poland were retrospectively analysed. RESULTS: During the first year of S-ICD introduction into the Polish health system 18 patients underwent surgery connected with S-ICDs. Majority of them (17 patients) were implanted de novo. In one patient surgical revision of a device implanted abroad was performed. Most of patients (78%) had S-ICDs implanted for secondary prevention. Inability of transvenous system implantation due to venous access obstruction or high risk of infection related with transvenous leads accounted for 83% of indications for S-ICD. Only in three patients were S-ICDs implanted due to young age and active mode of life. The implantations of S-ICDs were performed without important early or late complications. During follow-up one patient had episodes of ventricular arrhythmia successfully terminated with high-energy shocks. One patient died due to progression of heart failure. CONCLUSIONS: S-ICD implantation procedure has been successfully and safely introduced in Polish clinical routine. Nevertheless, despite clear indications in recent ESC guidelines, this therapy is not directly reimbursed in Poland and needs individual application for refund.

Baseline intrinsic heart rate and response to ivabradine treatment in patients with inappropriate sinus tachycardia.

BACKGROUND: Treatment with ivabradine became a new therapeutic alternative for patients with inappropriate sinus tachycardia (IST). The aim was to determine a relation between intrinsic heart rate (IHR) and response to ivabradine treatment. METHODS: Twenty-seven patients (mean age 37 ± 11; 23 women) with symptomatic IST despite medical treatment were recruited into the study. Resting ECG, 24-hr ECG monitoring (24hECG), exercise treadmill test, and symptoms evaluation were performed initially and after 60 days on ivabradine. IHR was acquired at baseline after pharmacological autonomic blockade. RESULTS: Nineteen patients (70%) were classified as abnormal IHR group (AIHR) while eight showed normal IHR (NIHR). No significant differences in ECG parameters were found between NIHR and AIHR subgroups, while baseline exercise capacity was higher in AIHR patients (10.9 vs. 9.5 METs, p < .05). Ivabradine treatment resulted in significant reduction in resting heart rate, average 24hECG heart rate, improvement in exercise capacity and reduction of symptoms in both subgroups. Nevertheless, favorable influence of ivabradine was significantly more exaggerated in AIHR subgroup (HR 116 vs. 90 bpm, av. HR 98 vs. 79 bpm, 10.9 vs. 13.6 METS, EHRA score 3.1 vs. 1.1, p < .001 for all) than in NIHR patients (HR 112 vs. 98 bpm, av. HR 97 vs. 88 bpm, 9.5 vs. 11.1 METs, EHRA score 3.1 vs. 1.9; p < .05 for all). CONCLUSIONS: Intrinsic heart rate may be useful in predicting response to ivabradine in patients with IST. More intense response to ivabradine in patients with AIHR may be attributed to different pathophysiological mechanisms underlying IST in AIHR and NIHR groups.

Bucindolol for the Maintenance of Sinus Rhythm in a Genotype-Defined HF Population: The GENETIC-AF Trial.

OBJECTIVES: The purpose of this study was to compare the effectiveness of bucindolol with that of metoprolol succinate for the maintenance of sinus rhythm in a genetically defined heart failure (HF) population with atrial fibrillation (AF). BACKGROUND: Bucindolol is a beta-blocker whose unique pharmacologic properties provide greater benefit in HF patients with reduced ejection fraction (HFrEF) who have the beta1-adrenergic receptor (ADRB1) Arg389Arg genotype. METHODS: A total of 267 HFrEF patients with a left ventricular ejection fraction (LVEF) <0.50, symptomatic AF, and the ADRB1 Arg389Arg genotype were randomized 1:1 to receive bucindolol or metoprolol therapy and were up-titrated to target doses. The primary endpoint of AF or atrial flutter (AFL) or all-cause mortality (ACM) was evaluated by electrocardiogram (ECG) during a 24-week period. RESULTS: The hazard ratio (HR) for the primary endpoint was 1.01 (95% confidence interval [CI]: 0.71 to 1.42), but trends for bucindolol benefit were observed in several subgroups. Precision therapeutic phenotyping revealed that a differential response to bucindolol was associated with the interval of time from the initial diagnoses of AF and HF to randomization and with the onset of AF relative to that of the initial HF diagnosis. In a cohort whose first AF and HF diagnoses were <12 years prior to randomization, in which AF onset did not precede HF by more than 2 years (n = 196), the HR was 0.54 (95% CI: 0.33 to 0.87; p = 0.011). CONCLUSIONS: Pharmacogenetically guided bucindolol therapy did not reduce the recurrence of AF/AFL or ACM compared to that of metoprolol therapy in HFrEF patients, but populations were identified who merited further investigation in future phase 3 trials.

Self-terminating ventricular fibrillation recorded by an implantable loop recorder as a cause of syncope - A case report.

Ventricular fibrillation (VF) is the most common arrhythmia leading to sudden cardiac death, but in rare cases VF can manifest as a syncope, provided that it will self-terminate. We present a case of a 45-year old female with a history of unexplained syncopal episodes despite exhaustive diagnostics. Implantable loop recorder documented an episode of idiopathic, self-terminating VF as a cause of syncope.

Rationale and design of the BUDAPEST-CRT Upgrade Study: a prospective, randomized, multicentre clinical trial.

AIMS: There is lack of conclusive evidence from randomized clinical trials on the efficacy and safety of upgrade to cardiac resynchronization therapy (CRT) in patients with implanted pacemakers (PM) or defibrillators (ICD) with reduced left ventricular ejection fraction (LVEF) and chronic heart failure (HF). The BUDAPEST-CRT Upgrade Study was designed to compare the efficacy and safety of CRT upgrade from conventional PM or ICD therapy in patients with intermittent or permanent right ventricular (RV) septal/apical pacing, reduced LVEF, and symptomatic HF. METHODS AND RESULTS: The BUDAPEST-CRT study is a prospective, randomized, multicentre, investigator-sponsored clinical trial. A total of 360 subjects will be enrolled with LVEF ≤ 35%, NYHA functional classes II-IVa, paced QRS ≥ 150 ms, and a RV pacing ≥ 20%. Patients will be followed for 12 months. Randomization is performed in a 3:2 ratio (CRT-D vs. ICD). The primary composite endpoint is all-cause mortality, a first HF event, or less than 15% reduction in left ventricular (LV) end-systolic volume at 12 months. Secondary endpoints are all-cause mortality, all-cause mortality or HF event, and LV volume reduction at 12 months. Tertiary endpoints include changes in quality of life, NYHA functional class, 6 min walk test, natriuretic peptides, and safety outcomes. CONCLUSION: The results of our prospective, randomized, multicentre clinical trial will provide important information on the role of cardiac resynchronization therapy with defibrillator (CRT-D) upgrade in patients with symptomatic HF, reduced LVEF, and wide-paced QRS with intermittent or permanent RV pacing. CLINICAL TRIALS.GOV IDENTIFIER: NCT02270840.

[Long-term prognosis in patients with vasovagal syncope after pacemaker implantation]. / Rokowanie odlegle u pacjentów z omdleniami wazowagalnymi po implantacji kardiostymulatora.

Patients with syncope, without presence of a structural or primary electrical disease, have a very good prognosis. On the other hand, recurring syncope has a negative impact on quality of life and involves a real risk of physical injuries. Vasovagal syncope usually requires no medical therapy and the most commonly recommended instruction include avoidance of fainting triggers, exercise that mainly provoke leg muscles tension, increase salt consumption and drink indicated amount of fluids. In the case cardioinhibitory type of vasovagal syncope the pacemaker implantation can consider. Unfortunately, not all patients benefit from this treatment. Medical society clearly highlights that proper qualification of VVS patients is the most important factor for cardiostimulator implantation. This article aims to summarize the most important research and guidelines concerning cardiac pacing for patients with vasovagal syncope.

[The role of reactive oxygen species (ROS) in arrhythmogenesis]. / Rola wolnych rodników tlenowych w patogenezie zaburzen rytmu serca.

Reactive oxygen species (ROS) are the molecular oxygen derivatives that have at least one unpaired electron. Thus, ROS easily react with a number of cell structures causing a change in their functions. ROS produced in small quantities positively affect many cellular mechanisms, but in excess are responsible for the formation of oxidative stress. Oxidative stress is considered a major cause of many diseases, including cardiovascular disease. Abolition of the adverse effects of ROS on organisms in order to maintain redox homeostasis is possible thanks to antioxidants. The research conducted mainly in recent years shows that the formation of arrhythmias may also be related to the phenomenon of oxidative stress. Oxidative damage to cell membranes in particular are causing changes in ion channel activity, which proper functioning is the basis for the formation of normal heart rhythm. Antioxidants seem to play a protective role against the formation of arrhythmias.

[Postural orthostatic tachycardia syndrome (POTS)--pathophysiology, diagnostics, and treatment]. / Zespól posturalnej tachykardii ortostatycznej (POTS)--patofizjologia, rozpoznanie i leczenie.

Postural orthostatic tachycardia syndrome (POTS) is one of the most common presentation of orthostatic intolerance. The syndrome is described as a multifactorial affliction. Main symptoms consist of persistent orthostatic tachycardia (heart rate increase at least 30 beats/min, lasting at least 10 min after assumic vertical position) with high noradrenalin serum concentration (measured in stand-up position). Additionally patients with POTS tend to have lover total blood volume. POTS is generally classified into dysatonomia disorders Symptoms in patients affected with POTS are chronic. The syndrome occurs predominantly in young women (approximately 80%). Due to complexity and variable intensity of symptoms POTS can severely impair daily activity and quality of life in otherwise healthy people. The correct diagnosis and identification of potential pathophysiological mechanisms of POTS is necessary before treatment administration. Adequate therapy can significantly reduce symptoms giving the patients a chance for a normal life.