Background:Studies have shown that the risk of new-onset heart failure (HF) is higher postimplantation for patients receiving right ventricular pacing. Objective:This study aimed to investigate incidence, risk factors, and implications for long-term prognosis of new-onset HF in patients after pacemaker implantation. Methods:Patients without pre-existing HF who received a pacemaker in Sweden during the period of 2005 to 2020 were identified via the nationwide Pacemaker Registry. Data were crossmatched with the population registry and national disease registries. The primary outcome was new-onset HF within 5 years, and a risk score for this was developed and validated. Results:In all, 65,579 patients met the inclusion criteria (10,351 single-chamber ventricular and 55,228 dual-chamber pacemakers). A total of 13,792 (21.0%) patients were diagnosed with HF within 5 years postimplantation. Of these, 6244 (45.3%) were hospitalized for HF. Patients with new-onset HF were more likely to die within 5 years (41.2% vs 19.7%, P < .0001). Risk factors for new-onset HF included increasing age, male sex, hypertension, diabetes, atrial fibrillation, chronic lung and kidney disease, ischemic heart disease, and atrioventricular block. In a combined score using these variables, patients in the highest risk-score quartile had a hazard ratio of 5.36 (95% CI 4.91-5.86, P < .001) and an absolute risk of 32% for developing HF. Conclusion:Pacemaker therapy is associated with >20% risk of new-onset HF within 5 years, and we identified 9 risk factors associated with the diagnosis of new-onset HF. The proposed score based on these variables can be used to identify patients at high risk for new-onset HF.

Abstract Aims Prior studies have suggested that the benefit from primary preventive defibrillator treatment for patients with nonischemic cardiomyopathyy, treated with cardiac resynchronization therapy, may be age-dependent. We aimed to compare age-stratified mortality rates and mode of death in patients with nonischemic cardiomyopathy who are treated with either primary preventive cardiac resynchronization therapy with defibrillator (CRT-D) or CRT with pacemaker (CRT-P). Methods and results All patients with nonischemic cardiomyopathy and CRT-P or primary preventive CRT-D who were implanted in Sweden during the period 2005–2020 were included. Propensity scoring was used to create a matched cohort. Primary outcome was all-cause mortality within 5 years. In all, 4027 patients were included: 2334 with CRT-P and 1693 with CRT-D. Crude 5-year mortality was 635 (27%) vs. 246 (15%), P < 0.001. In Cox regression analysis, adjusted for clinically relevant covariables, CRT-D was independently associated with higher 5-year survival [0.72 (0.61–0.85), P < 0.001]. Cardiovascular mortality was similar between groups (62 vs. 64%, P = 0.64), but death from heart failure was more common in the CRT-D group (46 vs. 36%, P = 0.007). In the matched cohort (n = 2414), 5-year mortality was 21% (24 vs. 16%, P < 0.001). In age-stratified analyses, CRT-P was associated with higher mortality in age groups <60 years and 70–79 years, but there was no difference in age groups 60–69 years or 80–89 years. Conclusion In this nationwide registry-based study, patients with CRT-D had better 5-year survival compared to patients with CRT-P. The interaction between age and mortality reduction was not consistent, but patients with CRT-D aged <60 years had the largest absolute mortality reduction.

BACKGROUND:Patients with chronic right ventricular (RV) pacing are at an increased risk of heart failure. Previous studies have indicated that cardiac resynchronization therapy (CRT) is underused in this setting, and that there may be sex-based differences in both CRT use and clinical outcome. OBJECTIVE:To evaluate sex-based differences in CRT use and clinical outcome for patients with new-onset heart failure post RV pacing. METHODS:Data from the Swedish pacemaker registry was matched with data from the national death and disease registries. Patients with de novo pacemaker implant due to AV block during the period 2005-2020 were included. New-onset heart-failure within two years post-implant was evaluated, primary outcome was all-cause mortality. RESULTS:In all, 30183 patients (37% female) were included. Women were on average 3 years older, but had less comorbidities than men. Median follow-up time was 4.5 [2.0-8.0] years. Women had better age- and comorbidity-adjusted survival (HR 0.78 [0.73-0.84], p < .001). For the 3560 patients (12.4% men and 10.7% women, p < .001) who were diagnosed with new-onset heart failure, 5-year mortality was similar for men and women (50% vs. 48%, p = .29). However, women were less likely to receive CRT-upgrade (3.8% vs. 9.1%, p < .001), and those who did were almost ten years younger than the men. CONCLUSION:Women with pacemaker due to AV block are older but have less comorbidities than men. They are less likely to develop new-onset heart failure, but also less likely to receive a CRT upgrade if they do develop heart failure. Increased awareness of the positive effects of CRT upgrade and potential sex- and age-based discrimination is warranted.

Background We aimed to evaluate if optimization by maximizing QRS duration (QRSd) reduction is feasible in an all-comer cardiac resynchronization therapy (CRT) population, and if reduced, QRSd is associated with a better clinical outcome. Methods Patients with LBBB receiving CRT implants during the period 2015-2020 were retrospectively evaluated. Implants from 2015-2017 were designated as controls. Starting from 2018, an active 12-lead electrogram-based optimization of QRSd reduction was implemented (intervention group). QRSd reduction was evaluated in a structured way at various device AV and VV settings, aiming to maximize the reduction. The primary endpoint was a composite of heart failure hospitalization or death from any cause. Results A total of 254 patients were followed for up to 6 years (median 2.9 [1.8-4.1]), during which 82 patients (32%) reached the primary endpoint; 53 deaths (21%) and 58 (23%) heart failure hospitalizations. Median QRS duration pre-implant was 162 ms [150-174] and post-implant 146ms [132-160]. Mean reduction in QRS duration was progressively larger for each year during the intervention period, ranging from - 9.5ms in the control group to - 24 in the year 2020 (p = 0.005). QRS reduction > 14 ms (median value) was associated with a lower risk of death or heart failure hospitalization (adjusted HR 0.54 [0.29-0.98] (p = 0.04). Conclusions Implementing a general strategy of CRT device optimization by aiming for shorter QRS duration is feasible in a structured clinical setting and results in larger reductions in QRS duration post-implant. In patients with a larger QRS reduction, compared to those with a smaller QRS reduction, there is an association with a better clinical outcome.

Abstract Background Left ventricular (LV) lead position may be an important factor for delivering effective cardiac resynchronization therapy (CRT). We therefore aimed to evaluate the effects of LV lead position, stratified by native QRS morphology, regarding the clinical outcome. Methods A total of 1295 CRT‐implanted patients were retrospectively evaluated. LV lead position was classified as lateral, anterior, inferior, or apical, and was determined using the left and right anterior oblique X‐ray views. Kaplan Meier and Cox regression were performed to evaluate the effects on all‐cause mortality and heart failure hospitalization, and the potential interaction between LV lead position and native ECG morphologies. Results A total of 1295 patients were included. Patients were aged 69 ± 7 years, 20% were female, 46% received a CRT‐Pacemaker (vs. CRT‐Defibrillator), mean LVEF was 25% ± 7%, and median follow‐up was 3.3 years [IQR 1.6–5–7 years]. Eight hundred and eighty‐two patients (68%) had a lateral LV lead location, 207 (16%) anterior, 155 (12%) apical, and 51 (4%) inferior. Patients with lateral LV lead position had larger QRS reduction (−13 ± 27 ms vs. −3 ± 24 ms, p < .001). Non‐lateral lead location was associated with a higher risk for all‐cause mortality (HR 1.34 [1.09–1.67], p = .007) and heart failure hospitalization (HR 1.25 [1.03–1.52], p = .03). This association was strongest for patients with native left or right bundle branch block, and not significant for patients with prior paced QRS or nonspecific intraventricular conduction delay. Conclusions In patients treated with CRT, non‐lateral LV lead positions (including apical, anterior, and inferior positions) were associated with worse clinical outcome and less reduction of QRS duration. This association was strongest for patients with native LBBB or RBBB.

The aim of the SYNSEQ (Left Ventricular Synchronous vs. Sequential MultiSpot Pacing for CRT) study was to evaluate the acute hemodynamic response (AHR) of simultaneous (3P-MPP syn) or sequential (3P-MPP seq) multi-3-point-left-ventricular (LV) pacing vs. single point pacing (SPP) in a group of patients at risk of a suboptimal response to cardiac resynchronization therapy (CRT). Twenty five patients with myocardial scar or QRS ≤ 150 or the absence of LBBB (age: 66 ± 12 years, QRS: 159 ± 12 ms, NYHA class II/III, LVEF ≤ 35%) underwent acute hemodynamic assessment by LV + dP/dtmax with a variety of LV pacing configurations at an optimized AV delay. The change in LV + dP/dt max (%ΔLV + dP/dt max) with 3P-MPP syn (15.6%, 95% CI: 8.8%-22.5%) was neither statistically significantly different to 3P-MPP seq (11.8%, 95% CI: 7.6-16.0%) nor to SPP basal (11.5%, 95% CI:7.1-15.9%) or SPP mid (12.2%, 95% CI:7.9-16.5%), but higher than SPP apical (10.6%, 95% CI:5.3-15.9%, p = 0.03). AHR (defined as a %ΔLV + dP/dt max ≥ 10%) varied between pacing configurations: 36% (9/25) for SPP apical, 44% (11/25) for SPP basal, 54% (13/24) for SPP mid, 56% (14/25) for 3P-MPP syn and 48% (11/23) for 3P-MPP seq.Fifteen patients (15/25, 60%) had an AHR in at least one pacing configuration. AHR was observed in 10/13 (77%) patients with a LBBB but only in 5/12 (42%) patients with a non-LBBB (p = 0.11). To conclude, simultaneous or sequential multipoint pacing compared to single point pacing did not improve the acute hemodynamic effect in a suboptimal CRT response population. Clinical Trial Registration:ClinicalTrials.gov, identifier: NCT02914457.

BACKGROUND Observational data suggest that an anterior or apical left ventricular (LV) position in cardiac resynchronization therapy (CRT) is associated with worse outcome and higher likelihood of "nonresponse." It is not known whether the benefits of optimizing LV lead position in a second procedure outweighs the procedural risks. OBJECTIVE To evaluate the clinical effects of LV lead repositioning. METHODS During the period 2015-2020, we identified all patients in whom the indication for the procedure was LV lead repositioning owing to "nonresponse" in combination with suboptimal LV lead position. All patients were followed with a structured visit 6 months post LV lead revision. Heart failure hospitalization and mortality data were gathered from the medical records and cross-checked with the population registry. RESULTS A total of 25 patients were identified who fulfilled the inclusion criteria. All procedures were successful in establishing LV lead pacing in a lateral mid or basal location. Median follow-up was 2.5 years [1.1-3.7]. There were improvements in NYHA class (mean -0.+/- 6 0.5 class, P,.001), LV ejection fraction (15 [interquartile range 2- 11] absolute %, P 5.01), QRS duration (-36 [-44 to -8], P,.001) and N-terminal pro-brain natriuretic peptide (NTproBNP) (-615 [-2837 to 1121] ng/L, P = .03). Clinical outcome was similar to a reference population with CRT (P = ns). CONCLUSION In nonresponders to CRT with either an anterior or inferior LV lead position, it was feasible to perform LV lead repositioning in all cases, with a low complication rate. Changing the LV lead position was associated with improved LV ejection fraction, larger QRS reduction, and larger NT-proBNP reduction.

Malpositioned pacemaker lead in the left ventricle (LV) is a rare procedural complication, which causes a special risk of thromboembolic events. Hence, prompt identification and early management of misplaced leads inside the LV is critical. Herein, we present a case of malpositioned pacemaker lead with transient ischemic attacks after the pacemaker implantation. The misplaced ventricular lead was discovered during regular echocardiography. Both leads were extracted percutaneously after dabigatran treatment. To our knowledge, this is the first report of uncomplicated percutaneous extraction of an inadvertently placed LV lead after dabigatran treatment. No neurologic events during a follow-up of 4 years.

Objectives. This study assessed the management approach and outcome of the pacemaker or implantable cardioverter-defibrillator (ICD) leads malpositioned in the left heart. Malpositioned leads (MPLs) may have deleterious consequences, and appropriate management remains uncertain. Methods. The study population included all patients referred to a single institution for MPL in the left side of the heart after pacemaker or ICD implantation during the period from 2015 to 2021. The approach and outcome of lead management were retrospectively assessed. Results. During the study period, 6887 patients underwent device implantation. MPL was diagnosed in five patients (0.07%). In four cases, the pacing lead was placed in a coronary sinus (CS) branch, while the pacing lead was inside the left ventricle (LV) in one case. Symptoms suggestive of lead malposition were reported by 2 patients (40%). One of the patients presented with recurrent TIAs. Another presented with inappropriate ICD shocks. In one asymptomatic case, an ICD lead changed position from the right ventricle to the CS, suggesting idiopathic lead migration. In 4/5 patients, the leads were removed or repositioned by percutaneous approach, with no major periprocedural complications. Conclusions. In this series of MPL in the left heart, two patients presented with thromboembolic events or inappropriate ICD shocks. These serious complications highlight the critical need for early correct diagnosis and proper management of MPL.

Knowledge of the coronary sinus (CS) anatomy is crucial for implantation of cardiac resynchronization therapy (CRT). Obstacles to CS entry, such as the Eustachian ridge and Thebesian valve, as well as within the CS, such as Vieussen’s valve and the vein of Marshall, are important to understand and differentiate during implantation or to identify earlier by imaging. Anatomic knowledge is mandatory to select the most suitable side branch for lead implantation. Modern tools and techniques almost always enable other anatomic problems, such as tortuous, small, short, or overly straight side branches, to also be overcome.

We present a case of combination of a leadless pacemaker (Micra) and a subcutaneous implantable cardioverter-defibrillator (S-ICD). The patient had a total of nine adequate shock treatments of ventricular fibrillation during 18 months of follow-up after the implantation. The shock treatments did not lead to any alteration in the Micra. All three sensing vectors of the S-ICD worked well. After 18 months, the functioning of both Micra and S-ICD continues to be uneventful. This case demonstrates that S-ICD combined with Micra may be a safe and feasible approach to provide pacing and ICD treatment without intracardiac leads.

Abstract Objectives. Comparisons between remote magnetic (RMN) and manual catheter navigation for atrial fibrillation (AF) ablation have earlier been reported with controversial results. However, these reports were based on earlier generations of the RMN system. Design. To evaluate the outcomes of the most current RMN system for AF ablation in a larger patient population with longer follow-up time, 112 patients with AF (78 paroxysmal, 34 persistent) who underwent AF ablation utilizing RMN (RMN group) were compared to 102 AF ablation patients (72 paroxysmal, 30 persistent) utilizing manual technique (Manual group). Results. The RMN group was associated with significantly shorter fluoroscopy time (10.4 ± 6.4 vs. 16.3 ± 10.9 min, p < .001) but used more RF energy (64.1 ± 19.4KJ vs. 54.3 ± 24.1 KJ, p < .05), while total procedure time showed no significant difference (201 ± 35 vs. 196 ± 44 min, NS). After 39 ± 9/44 ± 10 months of follow-up, AF-free rates at 1year, 2 years and 3.5 years post ablation were 63%, 46% and 42% in the RMN group vs. 60%, 32% and 30% (survival analysis p < .05) in the Manual group, whereas clinically effective rates were 82%, 73% and 70% for the former vs. 70%, 56% and 49% for the latter (survival analysis p < .005). Conclusion. Differing from previous reports, our data from a larger patient population and longer follow-up time demonstrates that compared to manual technique, the most current RMN technique is associated with better procedural and clinical outcomes for AF ablation.

Comparisons between remote magnetic navigation (RMN) and manual catheter navigation (Manual) for ablation of atrial fibrillation (AF) have earlier been reported with controversial results. We aim to compare the efficacy and outcome of these two methods for AF ablation based on our data from a larger

BackgroundCardiac resynchronization therapy (CRT) with or without a defibrillator has a positive effect on mortality and morbidity for patients with heart failure. However, comparisons between CRT‐defibrillators (CRT‐D) and CRT‐pacemakers (CRT‐P) are relatively scarce outside the clinical trial setting. This study aimed to assess baseline characteristics in relation to long‐term prognosis in patients treated with CRT, and to investigate the potential benefit of CRT‐D versus CRT‐P.MethodsData were retrospectively collected from the medical records of all consecutive patients treated with CRT‐P or primary prophylactic CRT‐D at a large tertiary care center between 1999 and 2012. Predictors of mortality were investigated, and time‐dependent analysis was performed with all‐cause mortality as the primary end point.ResultsA total of 705 patients were included (69.6 ± 10 years, 78% New York Heart Association classes III–IV, left ventricular ejection fraction median 25%, 16% female, 36% CRT‐D). The patients were followed for a median of 59 months. Annual mortality differed between CRT‐D primary prophylactic and CRT‐P groups (5.3% and 11.8%, respectively), but when adjusted for covariates, CRT‐D treatment (compared to CRT‐P) was not associated with better long‐term survival. Independent predictors of survival were: age, use of loop diuretics, hemoglobin levels, and use of renin angiotensin aldosterone system blockers.ConclusionsIn CRT treatment outside of the clinical trial setting, CRT‐D treatment was not an independent predictor of long‐term survival. Future research should focus on correct selection of the patients who receive enough benefit of an added defibrillator to justify CRT‐D implantation instead of CRT‐P treatment only.

Although rare, numerous case reports suggest that Thebesian veins confer increased morbidity and mortality. No study has evaluated their effects on cardiac structure or long-term patient outcomes. Patients undergoing coronary angiogram at the study institution from October 2002 and January 2015 were assessed for a diagnosis of prominent Thebesian veins. A matched control group was created and comparisons between clinical, echocardiographic, and survival measures were made. Of 50,116 total patients, 31 (0.06%) were found to have prominent Thebesian veins on angiography and were compared with a matched control group of 596 patients. Patients were matched for age, gender, angiogram date, location and extent of coronary disease, and dominance. Demographic and clinical data were similar between cohorts, with a median follow-up period of 26 months. Patients with Thebesian veins had lower Doppler E wave (0.7 vs 0.8; p = 0.007) and A wave (0.6 vs 0.8; p = 0.001) mitral inflow velocities suggesting some decrease in normal mitral inflow, potentially due to direct shunting into the ventricle from the Thebesian vein network. However, there was no observed difference in left ventricular size or ejection fraction between groups. There was also no significantly increased mortality associated with the presence of Thebesian veins (hazard ratio 1.11, 95% CI 0.58 to 2.13). In conclusion, although previous reports have suggested adverse outcomes from Thebesian veins, our case–control study demonstrated no significant associated adverse cardiac structural changes or increase in mortality, although patients with Thebesian veins were noted to have a decrease in mitral inflow velocities.

AIMS:Cardiac resynchronization therapy (CRT) has a well-documented positive effect on mortality and heart failure morbidity. The aim of this study was to assess the long-term survival and the predictive value of self-assessed functional status on the long-term prognosis of patients treated with CRT-pacemaker (CRT-P).METHODS AND RESULTS:Data were retrospectively collected from medical records of 446 consecutive patients implanted with CRT-P at a large-volume Swedish tertiary care centre. Primary outcome was all-cause mortality, predictive variables were assessed by log-rank test and univariate cox regression. Three hundred and nine patients had reliable information available on early improvement after implantation and were included in the multivariate analyses. The cohort was followed for a median of 79 months and was similar in baseline characteristics compared with major controlled trials. During follow-up 204 patients died, yearly mortality was 11.7%. Early improvement of self-assessed functional status was a strong independent predictor of survival [hazard ratio, HR 0.59, confidence interval (CI) 0.40-0.87, P = 0.007], together with well-known predictors; NYHA III-IV vs I-II (HR 1.66, CI 1.09-2.536, P = 0.018), age (HR 1.05, CI 1.03-1.08, P < 0.001), male gender (HR 2.0, CI 1.11-3.45, P = 0.021), and loop diuretic use (HR 4.41, CI 1.08-18.02). Patients with early improvement of self-assessed functional status had better 2-year and 5-year survival (P < 0.001).CONCLUSIONS:Real-life patient characteristics and predictors of outcome compare well with those in published prospective trials. Self-assessed functional status is a strong predictor of long-term survival, which may have implications for a more active follow-up of patients without spontaneous improvement.

Objectives. To determine whether a steerable catheter with electrogram guidance (CS-assist group) could facilitate access to the coronary sinus (CS) during cardiac resynchronization therapy (CRT) implantation. Design. Consecutive patients who underwent CRT implantation were recruited prospectively into the CS-assist group (n = 81) and compared with those using conventional techniques without an electrogram guidance (conventional group, n = 101). Results. The CS cannulation success rate was clearly greater in the CS-assist group (100%) than that in the conventional group (95%, p < 0.05), with significantly shorter mean procedure time (52.6 +/- 20.6 min vs. 73.2 +/- 40.9 min, p < 0.01) and fluoroscopy time (3.6 +/- 3.2 min vs. 14.2 +/- 20.4 min, p < 0.01). In the five CS cannulation failure cases, mean procedure time (144.0 +/- 37.0 min) and fluoroscopy time (57.8 +/- 24.8 min) were significantly longer than those in the other patients (61.2 +/- 32.3 and 8.2 +/- 13.6 min, respectively, n = 177, both p < 0.01). Conclusions. Using the steerable catheter with real-time electrogram guidance, location of and access to the CS is more rapid and successful, which may improve the success of the CRT implantation and may give significant time savings.

The aim of this study was to examine a possible role for extracellular pyrimidines as inotropic factors for the heart. First, nucleotide plasma levels were measured to evaluate whether UTP is released in patients with coronary heart disease. Then, inotropic effects of pyrimidines were examined in isolated mouse cardiomyocytes. Finally, expression of pyrimidine-selective receptors (a subgroup of the P2 receptors) was studied in human and mouse heart, using real time polymerase chain reaction, Western blot, and immunohistochemistry. Venous plasma levels of UTP were increased (57%) in patients with myocardial infarction. In electrically stimulated cardiomyocytes the stable P2Y 2/4 agonist UTPγS increased contraction by 52%, similar to β 1 -adrenergic stimulation with isoproterenol (65%). The P2Y 6 -agonist UDPβS also increased cardiomyocyte contraction (35%), an effect abolished by the P2Y 6 -blocker MRS2578. The phospholipase C inhibitor U73122 inhibited both the UDPβS and the UTPγS-induced inotropic effect, indicating an IP 3 -mediated effect via P2Y 6 receptors. The P2Y 14 agonist UDP-glucose was without effect. Quantification of mRNA with real time polymerase chain reaction revealed P2Y 2 as the most abundant pyrimidine receptor expressed in cardiomyocytes from man. Presence of P2Y 6 receptor mRNA was detected in both species and confirmed at protein level with Western blot and immunohistochemistry in man. In conclusion, UTP levels are increased in humans during myocardial infarction, giving the first evidence for UTP release in man. UTP is a cardiac inotropic factor most likely by activation of P2Y 2 receptors in man. For the first time we demonstrate inotropic effects of UDP, mediated by P2Y 6 receptors via an IP 3 -dependent pathway. Thus, the extracellular pyrimidines (UTP and UDP) could be important inotropic factors involved in the development of cardiac disease.

Peripheral arterial disease (PAD) is associated with platelet hyperaggregability as well as an increase in morbidity and mortality from myocardial infarction (MI) and stroke. Purinergic signaling has been shown, both experimentally and clinically, to play an important role in the activation of platelets. Platelets express three different purinergic receptors: P2Y1, P2Y12 and P2X1. We assessed the hypothesis that the hyperaggregability associated with PAD is partly due to an increased P2 receptor expression at the transcriptional and/or translational level. Patients with PAD (n=8) and controls (n=8) were studied. Using a high-resolution channelyzer, platelet shape change (PSC) was assessed by measuring the median platelet volume (MPV). The fall in free platelet count following the addition of ADP was also assessed. Real-time PCR was used to quantify the mRNA expression and Western blots to quantify the protein expression of P2 receptors in platelets. The median (and range) fall in free platelet count after adding ADP was significantly (P=0.02) greater for patients [11% (5-24); n=8] than for controls [0.5% (0-10); n=8] despite using a lower concentration of ADP for the patient samples. The MPV did not differ significantly. The mRNA levels for the three P2 receptors were similar in PAD patients and controls. Western blot detected no significant differences in protein expression between these groups. Thus, platelets from PAD patients show an increased activation after stimulation with ADP (even though all patients were on aspirin). This hyperactivity was neither due to an obvious up-regulation of the mRNA levels nor to altered protein levels of P2 receptors in the platelets. It is suggested that the increased sensitivity to ADP in PAD is caused by post-receptor mechanisms.