Age-stratified clinical outcome in patients with known heart failure who receive pacemaker-, resynchronization therapy- or defibrillator implants.

Introduction Patients with heart failure (HF) and bradycardia may be eligible for different types of cardiac implantable electronic devices (CIED), depending on presence of AV conduction disease, age and comorbidities. We aimed to assess prognosis for these patients, after CIED implantation, stratified for type of CIED device. Methods All patients with preexisting HF diagnosis who received a CIED with a right ventricular lead during the period 2005-2018 in Sweden were identified via the Pacemaker-registry. Data was crossmatched with the population registry and national disease registries. Outcome was 5-year risk of HF hospitalization, and mortality. Results 37745 patients were included in the study. Comparing demographics for ICD vs. pacemaker implants, median age was 66 years vs. 83 years, 20% vs. 41% were female, 64% vs. 50% had ischemic heart disease and 35% vs. 67% had atrial fibrillation (all p<0,001). 5-year mortality was highest in single-chamber pacemaker recipients (61% compared to average 40%, p<0.001) but proportion of cardiovascular mortality was highest for CRT recipients (68% vs 63% p<0.001). Adjusted mortality was higher for pacemaker-patients in all age decile groups (ranging from <60 to >90 years old, all p<0.001). HF hospitalization occurred in 28% (dual-chamber pacemaker) to 39% (CRT-P) of patients, and cause of death was HF in 15% (dual-chamber pacemaker) to 25% (CRT-D), all p<0.001. Conclusion In this large real-world cohort of CIED treated patients with prior heart failure, demography- and mortality-data indicate that clinicians chose devices according to the overall status of the patient. Heart failure related events occurred in all groups, but were more common in CRT-treated patients.

Sex-based differences in cardiac resynchronization therapy upgrade and outcome for patients with pacemaker and new-onset heart failure.

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.

Age-stratified comparison of prognosis in cardiac resynchronization therapy with or without prophylactic defibrillator for nonischemic cardiomyopathy-a nationwide cohort study.

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.

Association between left ventricular lead position and intrinsic QRS morphology with regard to clinical outcome in cardiac resynchronization therapy for heart failure.

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.

Maximizing QRS duration reduction in contemporary cardiac resynchronization therapy is feasible and shorter QRS duration is associated with better clinical outcome.

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.

Baseline QRS Area and Reduction in QRS Area Are Associated with Lower Mortality and Risk of Heart Failure Hospitalization after Cardiac Resynchronization Therapy.

INTRODUCTION: Cardiac resynchronization therapy (CRT) is an established treatment for heart failure in selected patients. However, current guideline indications do not accurately predict individual prognosis with CRT, and up to 30% are nonresponders. Previous studies have shown that QRS area reduction following CRT is associated with improved survival. This study evaluates the incremental value of using QRS area derived from digital electrocardiogram (ECG) recordings, preoperatively and during CRT pacing. METHODS: Medical records of 445 patients receiving CRT implants at a large-volume tertiary care center in Sweden were retrospectively evaluated. Digital ECG before and after CRT implantation were collected, and ECG parameters were analyzed in relation to a primary composite endpoint of heart failure hospitalization or death from any cause. RESULTS: 147 patients (33%) reached the primary endpoint (93 deaths and 103 heart failure hospitalizations) over a median follow-up time of 2.7 years. A larger preimplant QRS area (HR, 0.89; [0.85-0.93]; p = <0.0001; adjusted HR, 0.93; [0.88-0.98]; p = 0.011) and a larger QRS area reduction (HR, 0.92; [0.88-0.96]; p = <0.0001; adjusted HR, 0.95; [0.90-0.99]; p = 0.042) postimplant correlated with a reduced risk of reaching the primary endpoint. This association was seen in patients with native left bundle branch block morphology, nonspecific intraventricular conduction delay, or paced ECG morphology but not in patients with right bundle branch block. CONCLUSION: Larger preimplant QRS area and QRS area reduction were associated with better clinical outcome following CRT in this retrospective material. This knowledge could help optimize patient selection and postoperative management.

Adjuvant therapy in invasive intraductal papillary mucinous neoplasm (IPMN) of the pancreas: a systematic review.

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a cystic tumor with a disease spectrum ranging from low-grade dysplasia to invasive carcinoma. The evidence for adjuvant treatment in invasive IPMN is limited and mostly derived from studies in conventional pancreatic ductal adenocarcinoma (PDAC). We performed a systematic review focusing on all clinical studies concerning the efficacy of adjuvant therapy in patients with invasive IPMN. We identified 8 retrospective cohort studies, using either adjuvant chemotherapy alone (n=1), adjuvant radiotherapy alone (n=1) or adjuvant chemotherapy in combination with radiation (n=6). Adjuvant therapy was associated with a survival benefit in 7 out of the 8 studies. Specific survival benefit was noted for patients with node-positive disease, higher TNM stage, positive resection margins, poor differentiation and tubular subtype. We conclude that adjuvant therapy may be beneficial in invasive IPMN, but current data suggest that it should be given selectively based on individual tumor characteristics. Further prospective, randomized studies are warranted.