"Peace of Mind" After Mastectomy: A Scoping Review.

BACKGROUND: Many women eligible for breast conservation therapy (BCT) elect unilateral mastectomy (UM) with or without contralateral prophylactic mastectomy (CPM) and cite a desire for "peace of mind." This study aimed to characterize how peace of mind is defined and measured and how it relates to surgical choice. METHODS: Nine databases were searched for relevant articles through 8 October 2023, and data were extracted from articles meeting the inclusion criteria. RESULTS: The inclusion criteria were met by 20 studies. Most were prospective cohort studies (65%, 13/20). In the majority of the studies (72%, 13/18), Non-Hispanic white/Caucasian women comprised 80 % or more of the study's sample. Almost half of the studies used the phrase "peace of mind" in their publication (45%, 9/20), and few directly defined the construct (15%, 3/20). Instead, words representing an absence of peace of mind were common, specifically, "anxiety" (85%, 17/20), "fear" (75%, 15/20), and "concern" (75%, 15/20). Most of the studies (90%, 18/20) measured peace of mind indirectly using questionnaires validated for anxiety, fear, worry, distress, or concern, which were administered at multiple postoperative time points (55%, 11/20). Most of the studies (95%, 18/19) reported at least one statistically significant result showing no difference in peace of mind between BCT, UM, and/or CPM at their latest time of assessment. CONCLUSION: Peace of mind is largely framed around concepts that suggest its absence, namely, anxiety, fear, and concern. Existing literature suggests that peace of mind does not differ among average-risk women undergoing BCT, UM, or CPM. Shared surgical decisions should emphasize at least comparable emotional and/or psychosocial well-being between CPM and breast conservation.

Prediction of Intraperitoneal Adhesions in Repeated Cesarean Deliveries with Stria Gravidarum Scoring System: A Cross-sectional Study.

BACKGROUND: The preoperative prediction of intraperitoneal adhesion (IPA) before repeated cesarean deliveries (CD), which are becoming more prevalent, is crucial for maternal health. AIM: The aim of the study was to preoperatively predict IPA in repeated CD with the stria gravidarum (SG) scoring system. METHODS: A total of 167 patients with at least one previous CD at or beyond 37 weeks of gestation were analyzed. Preoperative SG was calculated according to the Davey scoring system: 0-2 score were defined as mild SG (Group 1; n: 94, 56.2%), and 3-8 score were defined as severe SG (Group 2; n = 73, 43.8%). Preoperative previous cesarean incision features were evaluated according to the Vancouver scar scale. IPA was evaluated according to the Nair's and modified Nair's scoring systems. RESULTS: Parity, younger age at first pregnancy, higher body mass index, number of previous CDs, rate of scar symptoms, Nair's and the modified Nair's scores were statistically significant in Group 2 (P = 0.01; P = 0.04; P = 0.007; P = 0.004; P < 0.001; P = 0.007; P = 0.02, respectively). Davey score ≥3 and Vancouver score ≥4.5 were determined as the cut-off value to predict IPA (P = 0.1 and 0.07, respectively). According to multivariate analysis, both Davey and Vancouver scores are independent factors in predicting IPA (P = 0.02 and 0.04, respectively). CONCLUSION: Evaluating the SG score through the Davey score in women with a history of previous CD may assist in predicting IPA status before the planning of a subsequent surgery.

Impact of artificial intelligence arrhythmia mapping on time to first ablation, procedure duration, and fluoroscopy use.

INTRODUCTION: Artificial intelligence (AI) ECG arrhythmia mapping provides arrhythmia source localization using 12-lead ECG data; whether this information impacts procedural efficiency is unknown. We performed a retrospective, case-control study to evaluate the hypothesis that AI ECG mapping may reduce time to ablation, procedural duration, and fluoroscopy. MATERIALS AND METHODS: Cases in which system output was used were retrospectively enrolled according to IRB-approved protocols at each site. Matched control cases were enrolled in reverse chronological order beginning on the last day for which the technology was unavailable. Controls were matched based upon physician, institution, arrhythmia, and a predetermined complexity rating. Procedural metrics, fluoroscopy data, and clinical outcomes were assessed from time-stamped medical records. RESULTS: The study group consisted of 28 patients (age 65 ± 11 years, 46% female, left atrial dimension 4.1 ± 0.9 cm, LVEF 50 ± 18%) and was similar to 28 controls. The most common arrhythmia types were atrial fibrillation (n = 10), premature ventricular complexes (n = 8), and ventricular tachycardia (n = 6). Use of the system was associated with a 19.0% reduction in time to ablation (133 ± 48 vs. 165 ± 49 min, p = 0.02), a 22.6% reduction in procedure duration (233 ± 51 vs. 301 ± 83 min, p < 0.001), and a 43.7% reduction in fluoroscopy (18.7 ± 13.3 vs. 33.2 ± 18.0 min, p < 0.001) versus controls. At 6 months follow-up, arrhythmia-free survival was 73.5% in the study group and 63.3% in the control group (p = 0.56). CONCLUSION: Use of forward-solution AI ECG mapping is associated with reductions in time to first ablation, procedure duration, and fluoroscopy without an adverse impact on procedure outcomes or complications.

Screening for precancerous anal lesions linked to human papillomaviruses: French recommendations for clinical practice.

In France, about 2000 new cases of anal cancer are diagnosed annually. Squamous cell carcinoma is the most common histological type, mostly occurring secondary to persistent HPV16 infection. Invasive cancer is preceded by precancerous lesions. In addition to patients with a personal history of precancerous lesions and anal cancer, three groups are at very high risk of anal cancer: (i) men who have sex with men and are living with HIV, (ii) women with a history of high-grade squamous intraepithelial lesions (HSILs) or vulvar HPV cancer, and (iii) women who received a solid organ transplant more than 10 years ago. The purpose of screening is to detect HSILs so that they can be treated, thereby reducing the risk of progression to cancer. All patients with symptoms should undergo a proctological examination including standard anoscopy. For asymptomatic patients at risk, an initial HPV16 test makes it possible to target patients at risk of HSILs likely to progress to cancer. Anal cytology is a sensitive test for HSIL detection. Its sensitivity is greater than 80% and exceeds that of proctological examination with standard anoscopy. It is indicated in the event of a positive HPV16 test. In the presence of cytological abnormalities and/or lesions and a suspicion of dysplasia on clinical examination, high-resolution anoscopy is indicated. Performance is superior to that of proctological examination with standard anoscopy. However, this technique is not widely available, which limits its use. If high-resolution anoscopy is not possible, screening by a standard proctological examination is an alternative. There is a need to develop high-resolution anoscopy and triage tests and to evaluate screening strategies.

Matched control analysis suggests that R-CHOP followed by (R)-ICE may improve outcome in non-GCB DLBCL compared with R-CHOP.

ABSTRACT: Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is considered the standard-of-care for patients with advanced-stage diffuse large B-cell lymphoma (DLBCL), despite findings that patients with nongerminal center B-cell like (non-GCB) have significantly worse outcome with this regimen. We evaluated the prognostic significance of baseline risk factors, including cell of origin (COO) classified by the Hans algorithm, within an alternative chemoimmunotherapy program. At Memorial Sloan Kettering Cancer Center (MSK), 151 patients with DLBCL received sequential R-CHOP induction and (R)-ICE (rituximab, ifosfamide, carboplatin, and etoposide) consolidation. Outcome analysis based on COO was validated with a propensity score-matched cohort treated with R-CHOP from the Mayo Clinic component of the Molecular Epidemiology Resource (MER). Among the patients with GCB (n = 69) and non-GCB (n = 69) at MSK, event-free survival (EFS) of non-GCB was superior to that of GCB (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.29-0.98). Overall survival (OS) demonstrated an association in the same direction but was not statistically significant (HR, 0.68; 95% CI, 0.33-1.42). Propensity score-matched patients from MSK (n = 108) demonstrated a small attenuation in the HRs for EFS (HR, 0.57; 95% CI, 0.27-1.18) and OS (HR, 0.76; 95% CI, 0.33-1.79) and were no longer statistically significant. In contrast, the matched MER cohort (n = 108) demonstrated an EFS association (HR, 1.17; 95% CI, 0.70-1.95) and OS association (HR, 1.13; 95% CI, 0.64-2.00) in the opposite direction, but were also not statistically significant. R-CHOP induction and (R)-ICE consolidation may overcome the negative prognostic impact of the non-GCB phenotype, per the Hans algorithm, and can be preferentially selected for this population. This trial was registered at www.ClinicalTrials.gov as #NCT00039195 and #NCT00712582.

The Predictors of Complete Pathologic Response in Rectal Cancer during the Total Neoadjuvant Therapy Era: A Systematic Review.

The modern rectal cancer treatment paradigm offers additional opportunities for organ preservation, most notably via total neoadjuvant therapy (TNT) and consideration for a watch-and-wait (WW) surveillance-only approach. A major barrier to widespread implementation of a WW approach to rectal cancer is the potential discordance between a clinical complete response (cCR) and a pathologic complete response (pCR). In the pre-TNT era, the identification of predictors of pCR after neoadjuvant therapy had been previously studied. However, the last meta-analysis to assess the summative evidence on this important treatment decision point predates the acceptance and dissemination of TNT strategies. The purpose of this systematic review was to assess preoperative predictors of pCR after TNT to guide the ideal selection criteria for WW in the current era. An exhaustive literature review was performed and the electronic databases Embase, Ovid, MEDLINE, PubMed, and Cochrane were comprehensively searched up to 27 June 2023. Search terms and their combinations included "rectal neoplasms", "total neoadjuvant therapy", and "pathologic complete response". Only studies in English were included. Randomized clinical trials or prospective/retrospective cohort studies of patients with clinical stage 2 or 3 rectal adenocarcinoma who underwent at least 8 weeks of neoadjuvant chemotherapy in addition to chemoradiotherapy with pCR as a measured study outcome were included. In this systematic review, nine studies were reviewed for characteristics positively or negatively associated with pCR or tumor response after TNT. The results were qualitatively grouped into four categories: (1) biochemical factors; (2) clinical factors; (3) patient demographics; and (4) treatment sequence for TNT. The heterogeneity of studies precluded meta-analysis. The level of evidence was low to very low. There is minimal data to support any clinicopathologic factors that either have a negative or positive relationship to pCR and tumor response after TNT. Additional data from long-term trials using TNT is critical to better inform those considering WW approaches following a cCR.

Engaging a Non-catalytic Cysteine Residue Drives Potent and Selective Inhibition of Caspase-6.

Caspases are a family of cysteine-dependent proteases with important cellular functions in inflammation and apoptosis, while also implicated in human diseases. Classical chemical tools to study caspase functions lack selectivity for specific caspase family members due to highly conserved active sites and catalytic machinery. To overcome this limitation, we targeted a non-catalytic cysteine residue (C264) unique to caspase-6 (C6), an enigmatic and understudied caspase isoform. Starting from disulfide ligands identified in a cysteine trapping screen, we used a structure-informed covalent ligand design to produce potent, irreversible inhibitors (3a) and chemoproteomic probes (13-t) of C6 that exhibit unprecedented selectivity over other caspase family members and high proteome selectivity. This approach and the new tools described will enable rigorous interrogation of the role of caspase-6 in developmental biology and in inflammatory and neurodegenerative diseases.

Time to second treatment can be used to predict overall survival in chronic lymphocytic leukemia: identifying risk factors to help guide treatment selection.

Targeted therapies have largely replaced chemoimmunotherapy (CIT) in first-line treatment of chronic lymphocytic leukemia (CLL). We aimed to develop a prognostic model to determine who would benefit from first-line CIT vs target therapy. In follicular lymphoma, time from diagnosis to second treatment (TT2T) correlates better with overall survival (OS) than time from diagnosis to first treatment (TT1T). We hypothesized that TT2T is a potential surrogate for OS in CLL. In a model-building cohort (n = 298), we evaluated potential predictors for TT2T and derived a risk score, which we validated in an external cohort (n = 1141). Our data demonstrated that TT2T and OS were more strongly correlated than TT1T and OS. Our risk score model consisted of three predictors (unmutated IGHV, ß2-microglobulin >297 nmol/L, and Rai stage I-IV), and was prognostic for TT2T and OS. TT2T is a promising surrogate for OS in CLL, but further validation is needed to establish this association.

Magnesium yields opposite effects on the nuclear and cytosolic cascades of apoptosis in different rat brain regions.

OBJECTIVE: Magnesium is considered as potential neuroprotective and therapeutic agent, but certain studies have provided evidence of its apoptotic effectiveness in neurons. We aimed to evaluate the possible apoptotic effects of long-term magnesium use in healthy adult rat brains. MATERIALS AND METHODS: Magnesium citrate and magnesium glycinate compounds were administered orally to rats for 8 weeks (36 mg/kg). Expression levels of Bcl-2, Bax and Cyt-C genes were analyzed by real-time polymerase chain reactions (RT-PCR) in the prefrontal cortex, hippocampus and striatum regions. Bcl-2, Bax and CytC protein levels were measured using ELISA kits. Tissue sections were evaluated histopathologically with hematoxylin-eosin staining. RESULTS: Compared to the control group, the magnesium-administered groups indicated gene expression reductions in almost all brain regions; pro-apoptotic Bax, anti-apoptotic Bcl-2 and Cyt-C gene expression levels were reduced. With magnesium, the Bcl-2 and Bax protein levels were increased. Bax/Bcl-2 gene and protein ratio were also increased in the striatum and hippocampus, whereas Cyt-C protein levels were decreased or did not change in the magnesium treated groups. There was no pathological finding in histological evaluation. CONCLUSIONS: Long-term magnesium usage can promote apoptotic cascade in brain tissue by increasing Bax/Bcl-2 ratio. Cyt-C, a prominent factor processing caspase pathway, was decreased or unchanged. In addition, taking into account the histological evaluation, we supposed that the absence of Cyt-C in the cytosol can prevent the subsequent apoptotic pathway. Consequently, we obtained the findings of apoptotic initiation with magnesium in brain, but this cascade seems to be arrested at later stages.

The impact of anti-CD20-based therapy on hypogammaglobulinemia in patients with follicular lymphoma.

Although treatment with anti-CD20 monoclonal antibodies (mAb) has improved outcomes in B-cell malignancies, it's associated with increased risk of hypogammaglobulinemia (HG). Our study aimed to determine the effects of anti-CD20 mAb on serum immunoglobulins (Ig) in follicular lymphoma (FL). Ig concentrations, infectious complications, and need for intravenous Ig were evaluated by level of exposure to anti-CD20 mAb in 380 patients. Prevalence of HG significantly differed by level of treatment exposure (p < 0.001). Single course anti-CD20 mAb was associated with rising IgG (+10.3 mg/dL/year), whereas the addition of maintenance therapy (-7.4 mg/dL/year) or multiple courses of treatment (-10.3 mg/dL/year) was associated with declining IgG. Among patients treated with anti-CD20 mAb, 45.2% developed IgG-HG and 10.3% developed symptomatic IgG-HG. Pretreatment IgG levels gradually declined in all patients, suggesting tumor burden may contribute to HG. Baseline and periodic monitoring of serum Ig is appropriate in patients with FL, including those managed with active surveillance.

Characteristics and outcomes of recurrent atrial fibrillation after prior failed pulmonary vein isolation.

BACKGROUND: The mechanisms for atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI) catheter ablation are unclear. Non-PV organized atrial arrhythmias (PAC, AT, macro-reentrant AFL) are possible contributors; however the prevalence and effect of their ablation on recurrent AF are unknown. We hypothesize that the identification and ablation of non-PV organized atrial arrhythmias were associated with less AF recurrence. METHODS: Patients who underwent repeat ablation for recurrent AF after prior PVI were retrospectively enrolled. The prevalence and characteristics of PV reconnections and non-PV organized atrial arrhythmias were identified. The outcomes of time to clinical AF recurrence, heart failure (HF) hospitalization, and mortality were analyzed in patients using multivariable adjusted Cox regression. RESULTS: In 74 patients with recurrent AF (age 66 ± 9 years, left atrial volume index 38 ± 10 ml/m2, 59% persistent AF), PV reconnections were found in 46 patients (61%), macro-reentrant atrial flutter in 27 patients (36%), and focal tachycardia in 12 patients (16%). Mapping and ablation of non-PV organized atrial arrhythmias were associated with a reduced recurrence of late clinical AF (adjusted HR 0.26, CI 0.08-0.85, p = 0.03) and the composite outcome of recurrence of late AF, HF hospitalization, and mortality (adjusted HR 0.38, CI 0.17-0.85, p = 0.02), with median follow-up of 1.6 (IQR 0.7-6.3) years. The presence of PV reconnections or empiric linear ablation was not associated with reduction in clinical AF or composite endpoints. CONCLUSION: The ablation of non-PV organized atrial arrhythmias resulted in a reduction of late clinical AF recurrence and composite outcome. In this challenging population, alternate mechanisms beyond PV reconnections need to be considered. Prospective studies are needed.

Open Versus Arthroscopic Surgical Management for Recalcitrant Trochanteric Bursitis: A Systematic Review.

Background: While excision of the trochanteric bursae to treat lateral hip pain has increased in popularity, no comparison exists between the surgical outcomes and complications of the open and arthroscopic techniques involving trochanteric bursectomy. The purpose of this study was to determine the efficacies and complication rates of arthroscopic and open techniques for procedures involving trochanteric bursectomy. Methods: The terms "trochanteric," "bursectomy," "arthroscopic," "open," "outcomes," and "hip" were searched in five electronic databases. Fifteen studies from 120 initial results were included. Patient-reported outcomes (PRO), pain, satisfaction, and complications were included for analysis. Results: Five hundred-two hips in 474 total patients (77.7% female) were included in this study. The average age was 54. The fourteen distinct PRO scores that were reported by the included studies improved significantly from baseline to final mean follow-up (12-70.8 months for open; 12-42 months for arthroscopic) for both approaches, demonstrating statistically significant patient benefit in a variety of hip arthroscopy settings (P > 0.05). The complication rates of all procedures ranged from 0%-33% and failure to improve pain ranged from 0%-8%. Patient satisfaction with surgery was high at 95% and 82% reported a willingness to undergo the same surgery again. No significant mean differences were found between the open and arthroscopic techniques. Conclusion: The open and arthroscopic approaches for trochanteric bursectomy are both safe and effective procedures in treating refractory lateral hip pain. No significant differences in PROs, pain, total complications, severity of complications, and total failures were seen between technique outcomes.Level of Evidence: IV.

Computational ECG mapping and respiratory gating to optimize stereotactic ablative radiotherapy workflow for refractory ventricular tachycardia.

BACKGROUND: Stereotactic ablative radiotherapy (SAbR) is an emerging therapy for refractory ventricular tachycardia (VT). However, the current workflow is complicated, and the precision and safety in patients with significant cardiorespiratory motion and VT targets near the stomach may be suboptimal. OBJECTIVE: We hypothesized that automated 12-lead electrocardiogram (ECG) mapping and respiratory-gated therapy may improve the ease and precision of SAbR planning and facilitate safe radiation delivery in patients with refractory VT. METHODS: Consecutive patients with refractory VT were studied at 2 hospitals. VT exit sites were localized using a 3-D computational ECG algorithm noninvasively and compared to available prior invasive mapping. Radiotherapy (25 Gy) was delivered at end-expiration when cardiac respiratory motion was ≥0.6 cm or targets were ≤2 cm from the stomach. RESULTS: In 6 patients (ejection fraction 29% ± 13%), 4.2 ± 2.3 VT morphologies per patient were mapped. Overall, 7 out of 7 computational ECG mappings (100%) colocalized to the identical cardiac segment when prior invasive electrophysiology study was available. Respiratory gating was associated with smaller planning target volumes compared to nongated volumes (71 ± 7 vs 153 ± 35 cc, P < .01). In 2 patients with inferior wall VT targets close to the stomach (6 mm proximity) or significant respiratory motion (22 mm excursion), no GI complications were observed at 9- and 12-month follow-up. Implantable cardioverter-defibrillator shocks decreased from 23 ± 12 shocks/patient to 0.67 ± 1.0 (P < .001) post-SAbR at 6.0 ± 4.9 months follow-up. CONCLUSIONS: A workflow including computational ECG mapping and protocol-guided respiratory gating is feasible, is safe, and may improve the ease of SAbR planning. Studies to validate this workflow in larger populations are required.

Enhanced Antiviral Function of Magnesium Chloride-Modified Heparin on a Broad Spectrum of Viruses.

Previous studies reported on the broad-spectrum antiviral function of heparin. Here we investigated the antiviral function of magnesium-modified heparin and found that modified heparin displayed a significantly enhanced antiviral function against human adenovirus (HAdV) in immortalized and primary cells. Nuclear magnetic resonance analyses revealed a conformational change of heparin when complexed with magnesium. To broadly explore this discovery, we tested the antiviral function of modified heparin against herpes simplex virus type 1 (HSV-1) and found that the replication of HSV-1 was even further decreased compared to aciclovir. Moreover, we investigated the antiviral effect against the new severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and measured a 55-fold decreased viral load in the supernatant of infected cells associated with a 38-fold decrease in virus growth. The advantage of our modified heparin is an increased antiviral effect compared to regular heparin.

Mutation Status and Immunohistochemical Correlation of EGFR Mutations in Gastrointestinal Stromal Tumors.

Being one of the leading causes of cancer deaths worldwide and their resistance to conventional treatment methods, made gastrointestinal stromal tumors (GISTs) one of the hot topics in medical research areas in the past decade. To investigate molecular alterations underlying the tumor is of great importance to be able to develop new, targeted treatment options. In this study, GIST samples obtained from 40 Turkish patients were analyzed for actionable epidermal growth factor receptor (EGFR) mutations that are related to treatment regimes in non small cell lung cancer (NSCLC) to understand whether EGFR expression is altered in GISTs. Established alterations in EGFR can make the use of tyrosine kinase inhibitors possible, which are currently used in cancer therapy, especially in NSCLC. Our results indicated that EGFR mutations are rare in GISTs. Further research is needed to sequence whole coding regions of the gene to investigate new actionable mutations in EGFR in an increased sample size.

Fasciculoventricular and atrioventricular accessory pathways in patients with Danon disease and preexcitation: A multicenter experience.

BACKGROUND: Studies have suggested that a fasciculoventricular pathway (FVP) may be the cause of preexcitation in patients with Danon disease, a rare X-linked dominant genetic disorder of hypertrophic cardiomyopathy. OBJECTIVE: The purpose of this study was to describe the prevalence of ventricular preexcitation on resting 12-lead electrocardiogram (ECG) in patients with Danon disease and the electrophysiological study (EPS) results of those with preexcitation. METHODS: Patients with confirmed Danon disease diagnosed with preexcitation (PR ≤120 ms, delta wave, QRS >110 ms) on ECG were included from a multicenter registry. The incidence of arrhythmias, implantable cardioverter-defibrillator (ICD) procedures, ICD shocks, and EPS results were collected. RESULTS: Thirteen of 40 patients (32.5%) with Danon disease were found to have preexcitation (mean age 17.3 years; 38% women). EPS performed in 9 of 13 patients (69%) demonstrated FVP only in 2 (22.2%), extranodal pathway without exclusion of FVP in 2 (22.2%), and both FVP and extranodal pathway in 5 (55.6%). Two patients had malignant accessory pathway (AP) properties. Over median follow-up of 842 days (interquartile range 138-1678), 11 patients (85%) had ICD placement, and 6 (46.1%) underwent heart transplantation. No patients required therapy for ventricular tachycardia, and 2 patients (15%) had paroxysmal atrial fibrillation. CONCLUSION: In a large multicenter cohort of patients with Danon disease, there was a high prevalence of FVP and extranodal pathways diagnosed on EPS in those with preexcitation. These findings suggest patients with preexcitation and Danon disease should undergo EPS to assess for FVP and potentially malignant extranodal AP.

Effect of closed loop stimulation versus accelerometer on outcomes with cardiac resynchronization therapy: the CLASS trial.

PURPOSE: Chronotropic incompetence (CI) in patients with heart failure is common and associated with impaired exercise intolerance and adverse outcomes. This study sought to determine the effects of closed loop stimulation (CLS) rate-adaptive pacing on functional capacity in patients with heart failure with reduced ejection fraction (HFrEF) and CI implanted with cardiac resynchronization therapy (CRT) devices. METHODS: A randomized, blinded, cross-over designed trial enrolled patients with HFrEF and CI implanted with a Biotronik CRT-D to complete a quality of life questionnaire, 6-min walk distance (6MWD), and cardiopulmonary exercise testing after two programmed periods: 1-week period of CLS and 1-week period of standard accelerometer (DDDR). RESULTS: Nine patients (6 males, mean age 71.4 years, 7 with New York Heart Association Class III, mean ejection fraction 39 ± 8%) were enrolled. Quality of life trended higher in CLS as compared to DDDR (550.8 ± 123.9 vs 489.3 ± 164.9, p = 0.06). There were no differences between CLS and DDDR in 6MWD (293.1 ± 90.2 m vs 315.1 ± 95.5 m, p = 0.52), peak heart rate (HR) 110.7 ± 14.7 bpm vs 109.7 bpm ± 14.1, p = 0.67), or peak VO2 (12.3 ± 4.9 ml/kg/min vs 12.9 ± 5.9, p = 0.47). As tests were submaximal as indicated by low respiratory exchange ratios (0.98 ± 0.11 vs 1.0 ± 0.8, p = 0.35), VE/VCO2 slope also showed no difference between CLS and DDDR (35.8 ± 5.6 vs 35.4 ± 5.7, p = 0.65). Five patients (56%) preferred CLS programming (p = 1.0). CONCLUSIONS: In patients with HFrEF and CI implanted with a CRT-D, peak HR, peak VO2, and 6MWD were equivalent, while there was a trend toward improved quality of life in CLS as compared to DDDR. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02693262.