Reduction of left ventricular global longitudinal strain in patients with permanent pacemakers as a predictor of heart failure and mortality outcomes.

INTRODUCTION: Frequent right ventricular (RV) pacing is associated with cardiomyopathy. The impact of RV pacing on left ventricular (LV) global longitudinal strain (GLS) and clinical outcomes is unclear. METHODS: We analyzed GLS via two-dimensional speckle tracking and LV ejection fraction (EF) on pre- and post-implantation transthoracic echocardiograms of patients undergoing dual chamber pacemaker implantation. We collected long-term data on strain, LVEF, and clinical outcomes. RESULTS: One hundred and ten patients (mean age 76 ± 12 years; 59 [54%] female) were followed for mean 23 ± 17 months. Mean baseline LVEF was 58 ± 11% and mean GLS was -17 ± 4%. Twenty-four (22%) patients had an absolute decrease in LVEF > 10% and 43 (39%) patients had a relative reduction of GLS > 15%. Among patients with a reduction of GLS, a larger proportion of patients had RV pacing burden ≥20% (67% vs. 46%; p = .048). Compared to patients without GLS reduction, more patients with a reduction in GLS reached a composite endpoint of HF hospitalization, CRT upgrade or death (47% vs. 16%; p = .001). CONCLUSION: Reduction in LV GLS was seen in nearly four in 10 patients undergoing pacemaker implantation and was significantly associated with increased RV pacing burden. LV GLS reduction was associated with increased risk of adverse outcomes. LV GLS may have utility in predicting outcomes among patients with RV pacing.

Troponin and Other Biomarker Levels and Outcomes Among Patients Hospitalized With COVID-19: Derivation and Validation of the HA2T2 COVID-19 Mortality Risk Score.

Background The independent prognostic value of troponin and other biomarker elevation among patients with coronavirus disease 2019 (COVID-19) are unclear. We sought to characterize biomarker levels in patients hospitalized with COVID-19 and develop and validate a mortality risk score. Methods and Results An observational cohort study of 1053 patients with COVID-19 was conducted. Patients with all of the following biomarkers measured-troponin-I, B-type natriuretic peptide, C-reactive protein, ferritin, and d-dimer (n=446) -were identified. Maximum levels for each biomarker were recorded. The primary end point was 30-day in-hospital mortality. Multivariable logistic regression was used to construct a mortality risk score. Validation of the risk score was performed using an independent patient cohort (n=440). Mean age of patients was 65.0±15.2 years and 65.3% were men. Overall, 444 (99.6%) had elevation of any biomarker. Among tested biomarkers, troponin-I ≥0.34 ng/mL was the only independent predictor of 30-day mortality (adjusted odds ratio, 4.38; P<0.001). Patients with a mortality score using hypoxia on presentation, age, and troponin-I elevation, age (HA2T2) ≥3 had a 30-day mortality of 43.7% while those with a score <3 had mortality of 5.9%. Area under the receiver operating characteristic curve of the HA2T2 score was 0.834 for the derivation cohort and 0.784 for the validation cohort. Conclusions Elevated troponin and other biomarker levels are commonly seen in patients hospitalized with COVID-19. High troponin levels are a potent predictor of 30-day in-hospital mortality. A simple risk score can stratify patients at risk for COVID-19-associated mortality.

Outcomes and mortality associated with atrial arrhythmias among patients hospitalized with COVID-19.

INTRODUCTION: The impact of atrial arrhythmias on coronavirus disease 2019 (COVID-19)-associated outcomes are unclear. We sought to identify prevalence, risk factors and outcomes associated with atrial arrhythmias among patients hospitalized with COVID-19. METHODS: An observational cohort study of 1053 patients with severe acute respiratory syndrome coronavirus 2 infection admitted to a quaternary care hospital and a community hospital was conducted. Data from electrocardiographic and telemetry were collected to identify atrial fibrillation (AF) or atrial flutter/tachycardia (AFL). The association between atrial arrhythmias and 30-day mortality was assessed with multivariable analysis. RESULTS: Mean age of patients was 62 ± 17 years and 62% were men. Atrial arrhythmias were identified in 166 (15.8%) patients, with AF in 154 (14.6%) patients and AFL in 40 (3.8%) patients. Newly detected atrial arrhythmias occurred in 101 (9.6%) patients. Age, male sex, prior AF, renal disease, and hypoxia on presentation were independently associated with AF/AFL occurrence. Compared with patients without AF/AFL, patients with AF/AFL had significantly higher levels of troponin, B-type natriuretic peptide, C-reactive protein, ferritin and d-dimer. Mortality was significantly higher among patients with AF/AFL (39.2%) compared to patients without (13.4%; p < .001). After adjustment for age and co-morbidities, AF/AFL (adjusted odds ratio [OR]: 1.93; p = .007) and newly detected AF/AFL (adjusted OR: 2.87; p < .001) were independently associated with 30-day mortality. CONCLUSION: Atrial arrhythmias are common among patients hospitalized with COVID-19. The presence of AF/AFL tracked with markers of inflammation and cardiac injury. Atrial arrhythmias were independently associated with increased mortality.

Linking Arrhythmias and Adipocytes: Insights, Mechanisms, and Future Directions.

Obesity and atrial fibrillation have risen to epidemic levels worldwide and may continue to grow over the next decades. Emerging evidence suggests that obesity promotes atrial and ventricular arrhythmias. This has led to trials employing various strategies with the ultimate goal of decreasing the atrial arrhythmic burden in obese patients. The effectiveness of these interventions remains to be determined. Obesity is defined by the expansion of adipose mass, making adipocytes a prime candidate to mediate the pro-arrhythmogenic effects of obesity. The molecular mechanisms linking obesity and adipocytes to increased arrhythmogenicity in both the atria and ventricles remain poorly understood. In this focused review, we highlight areas of potential molecular interplay between adipocytes and cardiomyocytes. The effects of adipocytes may be direct, local or remote. Direct effect refers to adipocyte or fatty infiltration of the atrial and ventricular myocardium itself, possibly causing increased dispersion of normal myocardial electrical signals and fibrotic substrate of adipocytes that promote reentry or adipocytes serving as a direct source of aberrant signals. Local effects may originate from nearby adipose depots, specifically epicardial adipose tissue (EAT) and pericardial adipose tissue, which may play a role in the secretion of adipokines and chemokines that can incite inflammation given the direct contact and disrupt the conduction system. Adipocytes can also have a remote effect on the myocardium arising from their systemic secretion of adipokines, cytokines and metabolites. These factors may lead to mitochondrial dysfunction, oxidative stress, autophagy, mitophagy, autonomic dysfunction, and cardiomyocyte death to ultimately produce a pro-arrhythmogenic state. By better understanding the molecular mechanisms connecting dysfunctional adipocytes and arrhythmias, novel therapies may be developed to sever the link between obesity and arrhythmias.

Feasibility of Performing Radiofrequency Catheter Ablation and Endomyocardial Biopsy in the Same Setting.

In patients with unexplained cardiomyopathy, electroanatomical mapping can identify abnormal tissue to target during electrophysiology-guided endomyocardial biopsy (EP-guided EMB). The objective of this study is to determine whether catheter ablation performed in the same setting as EP-guided EMB increases procedural risk. Sixty-seven patients (mean age 54.4 ± 13.8, 57% male) undergoing EP-guided EMB were included. Radiofrequency catheter ablation was performed in 17 patients (25%) for ventricular arrhythmias and in 2 (3%) for typical atrial flutter. Femoral arterial access was obtained in 90% ablation patients and 40% biopsy-only patients; vascular access complications were more common in the ablation group than in the EMB-only group (p = 0.02). There were no significant differences in rate of tricuspid regurgitation, thromboembolism, or pericardial effusion, whether procedural anticoagulation was used. In conclusion, catheter ablation and procedural anticoagulation can be combined with EP-guided EMB with an increased risk of vascular access complications, but no significant increase in intracardiac complications.

Right ventricular pacemaker lead position is associated with differences in long-term outcomes and complications.

INTRODUCTION: Cardiac pacing from the right ventricular apex is associated with detrimental long-term effects and nonapical pacing locations may be associated with improved outcomes. There is little data regarding complications with nonapical lead positions. The aim of this study was to assess long-term outcomes and lead-related complications associated with differing ventricular lead tip position. METHODS AND RESULTS: All adult patients who underwent dual-chamber pacemaker implantation from 2004 to 2014 were included if they had postprocedure chest radiographs amenable to lead position determination. Long-term outcomes and lead-related complication rates were recorded. These were compared at 5 years between: (1) apical and septal leads, (2) apical and nonseptal nonapical (NSNA), and (3) apical and septal with >40% ventricular pacing. We retrospectively evaluated 3,450 patients, which included 238 with a septal position and 733 with NSNA lead positions. Septal lead position was associated with a lower mortality compared to apical leads (24% vs. 31%, P = 0.02). In patients with greater than 40% pacing, septal leads were associated with significantly higher rates of incident atrial fibrillation compared to apical leads (49% vs. 34%, P = 0.04). NSNA positions were associated with a significantly higher rate of lead dislodgement (4% vs. 2%, P = 0.005) and need for revision (8% vs. 5%, P = 0.005). CONCLUSIONS: Septal pacemaker lead position is associated with a lower mortality compared to apically placed leads, but a higher incidence of atrial fibrillation with higher percentage ventricular pacing. NSNA lead locations are associated with more complications and should be avoided.

Effect of Ventricular Arrhythmia Ablation in Patients With Heart Mate II Left Ventricular Assist Devices: An Evaluation of Ablation Therapy.

BACKGROUND: Patients with advanced heart failure (HF) are predisposed to ventricular arrhythmias (VAs), particularly following implantation of a left ventricular assist device (LVAD). There is minimal evidence for appropriate management strategies. OBJECTIVES: This study aimed to compare the burden of VA and response to ablation performed either before or following LVAD implantation. METHODS: We created a retrospective cohort of patients who underwent both VA ablation and Heart Mate II (Thoratec, Pleasanton, CA, USA) LVAD implantation at Mayo Clinic (Rochester, MN, USA). Patients were stratified based on whether they underwent VA ablation before (pre-LVAD) or after LVAD (post-LVAD) implantation. Descriptive analyses assessed 6-month arrhythmia burden in relation to LVAD implantation and VA ablation. RESULTS: A total of 9 patients underwent both LVAD implantation and VA ablation. There were 3 and 6 patients, respectively, in the pre-LVAD and post-LVAD cohorts. Among patients in the pre-LVAD cohort, the median number of VAs tended to increase after ablation (9 vs. 72) and decreased after LVAD implantation (72 vs. 63). Similarly among patients in the post-LVAD cohort, the median burden of VAs increased after LVAD implantation (1 vs. 22) and the median burden decreased after ablation (22 vs. 13). Two of 6 patients had substrate related to the LVAD inflow cannula site, while other substrate was not related directly to the cannula. CONCLUSIONS: In patients with progressive HF and LVAD implantation, ablation is associated with reduced VA rates. In LVAD patients, most VAs arise from substrate unrelated to the inflow cannula site.

Right atrial lead fixation type and lead position are associated with significant variation in complications.

PURPOSE: Optimal atrial pacemaker lead position and fixation mechanism have not been determined with regard to effect on complications. We aimed to determine the association between atrial lead-related complications and varying atrial lead tip positions and lead fixation mechanisms. METHODS: All patients who underwent dual-chamber pacemaker implant between 2004 and 2014 were retrospectively reviewed for atrial lead tip position and fixation type. Lead-related complications were assessed by electronic medical record review. Complication rates were compared at 1 year by chi-square analysis and at 5 years using a Kaplan-Meier analysis. RESULTS: During the study period, 3451 patients (mean age 73.9, 53.4 % male) underwent dual-chamber pacemaker placement. Active fixation leads were associated with a higher incidence of pericardial effusion (81 (2.9 %) vs. 6 (1.0 %), p = 0.005) and pericardiocentesis (46 (1.6 %) vs. 2 (0.3 %), p = 0.01) at 1 year compared to passive fixation leads. There was no difference in overall complication rates by fixation type (161 (5.7 %) vs. 29 (4.6 %), p = 0.26). Low atrial septal lead tip position was associated with a higher rate of lead dislodgement (10 (15.2 %)) compared to appendage (46 (1.6 %)), free wall (10 (2.1 %)), or high atrial septal (2 (4.7 %)) positions (p < 0.001). This difference was also reflected in a significantly increased need for lead revision and overall complications. A multivariate analysis which included potential confounders confirmed the association of active fixation leads with an increased rate of perforation-related complications (p = 0.03) and septal lead location with increased rates of dislodgement (p < 0.001). CONCLUSIONS: Active compared to passive lead fixation increases the risk for pericardial effusion requiring pericardiocentesis. There is a clear association between low atrial septal lead position and lead dislodgement requiring lead revision.