PD-L1 testing in metastatic triple negative breast cancer: Results of an Italian survey.

BACKGROUND: Immunotherapy has revolutionized the approach to metastatic triple-negative breast cancers. Atezolizumab was approved for patients with metastatic triple-negative breast cancers whose tumors express PD-L1, determined by SP 142 assay. To assess the availability and practice of SP142 test we administered a survey to all the 15 pathology departments of the Lazio Region during a six-month period. METHODS: The survey comprised 12 questions regarding the availability of SP142 in the pathology departments, the percentage of positive tests, the difficulties of pathologists in cases close to cut-off value and the tested samples. RESULTS: The SP142 assay was available in only eight centers. In case of positive result, most centers (5/8, 62.5%) reported values of PD-L1 expression ranging from > 1 to ⩽ 5%, with values close to the cut-off point (⩾ 1% or < 1%) being the greatest challenge.Most of the centers (6/8, 75%) tested material from both their own and other hospitals. In most centers, the evaluations were performed either on primary tumors or metastasis, in particular lymph nodes (5/8, 62.5%), followed by lung (3/8, 37.5%) and liver (1/8, 12.5%) metastasis. CONCLUSION: Our results raise some important issues concerning the evaluation of PD-L1 in the "real-life" setting, providing strategies for its implementation.

Association Between Quality of Life and Procedural Outcome After Catheter Ablation for Atrial Fibrillation: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Catheter ablation is effective in reducing atrial fibrillation (AF), but the association of ablation for AF with quality of life is unclear. Objective: To evaluate whether the procedural outcome of ablation for AF is associated with quality of life (QOL) measures. Design, Setting, and Participants: This was a prespecified secondary analysis of the Substrate and Trigger Ablation for Reduction of Atrial Fibrillation-Part II (STAR AF II) prospective randomized clinical trial, which compared 3 strategies for ablation of persistent AF. This analysis included 549 of the 589 patients enrolled in the trial who underwent ablation. Enrollment occurred at 35 centers in Europe, Canada, Australia, China, and Korea from November 2010 to July 2012. Data for the current study were analyzed on December 11, 2019. Interventions: Patients underwent AF ablation with 1 of 3 ablation strategies: (1) pulmonary vein isolation (PVI), (2) PVI plus complex fractionated electrograms, or (3) PVI plus linear lesions. Main Outcomes and Measures: Quality of life was assessed at baseline and at 6, 12, and 18 months after ablation for AF using the 36-Item Short Form Health Survey and the EuroQol Health-Related Quality of Life 5-Dimension 3-Level questionnaire. Scores were also converted to a physical health component score (PCS) and a mental health component score (MCS). Individual AF burden was calculated by the total time with AF from Holter monitors and the percentage of transtelephonic monitor recordings showing AF. Results: Among the 549 patients included in this secondary analysis, QOL was assessed in 466 (85%) at baseline and at 6, 12, and 18 months after ablation for AF. The mean (SD) age of the study population was 60 (9) years; 434 (79%) individuals were men, and 417 (76%) had continuous AF for 6 months or more before ablation. The AF burden significantly decreased from a mean (SD) of 82% (36%) before ablation to 6.6% (23%) after ablation (P < .001). Significant improvements in mean (SD) PCS (68.3 [20.7] to 82.5 [18.6]) and MCS (35.3 [8.6] to 37.5 [7.6]) occurred 18 months after ablation (P < .05 for both). Significant QOL improvement occurred in all 3 study arms and regardless of AF recurrence, defined as AF episodes lasting more than 30 seconds: for no recurrence, mean (SD) PCS increased from 66.5 (20.9) to 79.1 (19.4) and MCS from 35.3 (8.7) to 37.7 (7.7); for recurrence, mean (SD) PCS increased from 70.2 (20.4) to 86.4 (16.8) and MCS from 35.3 (8.6) to 37.1 (7.4) (P < .05 for all). When outcome was defined by AF burden reduction, in patients with less than 70% reduction in AF burden, the increase in PCS was significantly less than in those with greater than 70% reduction, and only 3 of 8 subscales showed significant improvement. Conclusions and Relevance: In this secondary analysis, decreases in AF burden after ablation for AF were significantly associated with improvements in QOL. Quality of life changes were significantly associated with the percentage of AF burden reduction after ablation. Trial Registration: ClinicalTrials.gov Identifier: NCT01203748.

Cardiac resynchronization therapy before and after MitraClip implantation: An advantageous upgrading to reduce mitral regurgitation.

MitraClip therapy has been proposed as therapeutic option in selected patients with degenerative or functional mitral regurgitation (FMR), leading to clinical and prognostic benefits. Previous studies demonstrated the safety and the efficacy of MitraClip therapy on symptoms and left ventricular remodeling in cardiac resynchronization therapy (CRT) non-responder patients. We report a case of a CRT non-responder patient treated with MitraClip implantation followed by a new upgrading of the CRT for persistent FMR at the follow-up. The optimization of the interventricular delay, guided by echocardiographic parameters, resulted in a significant clinical and functional benefit. Echo-guided CRT upgrading can provide additive efficacy for patients in whom MitraClip implantation does not significantly improve FMR and symptoms.

Impact of acute atrial fibrillation termination and prolongation of atrial fibrillation cycle length on the outcome of ablation of persistent atrial fibrillation: A substudy of the STAR AF II trial.

BACKGROUND: Controversy exists about the impact of acute atrial fibrillation (AF) termination and prolongation of atrial fibrillation cycle length (AFCL) during ablation on long-term procedural outcome. OBJECTIVE: The purpose of this study was to analyze the influence of AF termination and AFCL prolongation on freedom from AF in patients from the STAR AF II (Substrate and Trigger Ablation for Reduction of Atrial Fibrillation Trial-Part II) trial. METHODS: Acute changes in AFCL and AF termination were collected during the index procedure of the STAR AF II trial and compared to recurrence of AF at 18 months. Recurrence was assessed by ECG, Holter (3, 6, 9, 12, 18 months), and weekly transtelephonic ECG monitoring for 18 months. RESULTS: AF terminated in 8% of the pulmonary vein isolation (PVI) arm, 45% in the PVI+complex electrogram arm, and 22% of the PVI+linear ablation arm (P <.001), but freedom from AF did not differ among the 3 groups (P = .15). Freedom from AF was significantly higher in patients who presented to the laboratory in sinus rhythm (SR) compared to those without AF termination (63% vs 44%, P = .007). Patients with AF termination had an intermediate outcome (53%) that was not significantly different from those in SR (P = .84) or those who did not terminate (P = .08). AF termination was a univariable predictor of success (P = .007), but by multivariable analysis, presence of early SR was the strongest predictor of success (hazard ratio 0.67, P = .004). Prolongation of AFCL was not predictive of 18-month freedom from AF. CONCLUSION: Acute AF termination and prolongation in AFCL did not consistently predict 18-month freedom from AF. Presence of SR before or early during the ablation was the strongest predictor of better outcome.

Safety and efficiency of ventricular pacing prevention with an AAI-DDD changeover mode in patients with sinus node disease or atrioventricular block: impact on battery longevity-a sub-study of the ANSWER trial.

AIMS: This ANSWER (EvaluAtioN of the SafeR mode in patients With a dual chambER pacemaker indication) sub-study assesses safety and effectiveness of SafeR™ and the impact of ventricular pacing (VP) prevention on anticipated device longevity and replacement rate. METHODS AND RESULTS: Patients implanted for atrioventricular block (AVB, n = 310) or sinus node dysfunction (SND, n = 336) were randomly assigned to SafeR (n = 314) or DDD (n = 318) and followed for 36 months. Safety, median VP, estimated device longevity (mean difference, 95% confidence interval [CI]), and anticipated replacement rates were analysed by pacing mode and implant indication. No difference in mortality, syncope, or mode intolerance was observed between randomization groups regardless of the indication. Ventricular pacing on SafeR vs. DDD was 11.5 vs. 93.6% in the overall population (P < 0.001), 89.2 vs. 83.8% in permanent AVB (P = 0.944), 53.5 vs. 98.2% in intermittent AVB (P < 0.001), and 2.2 vs. 84.7% in SND (P < 0.001). Anticipated median device longevity increased on SafeR by 14 [Q1 10; Q3 17] months [10; 17] (P < 0.001) in the overall population, 9 months [-5; 22] (P = 0.193) in permanent AVB, 14 months [8; 19] (P < 0.001) in intermittent AVB, and 14 months [9; 19] (P < 0.001) in SND. In intermittent AVB and SND, prolonged estimated battery longevity translated into the prevention of one anticipated replacement in at least 23% of patients. CONCLUSION: SafeR was effective in reducing VP in intermittent AVB and in SND. No effect was observed in permanent AVB. No safety issue was observed. Ventricular pacing reduction by SafeR translated into relevant estimated prolongation of device longevity and anticipated reduction of required replacements.

Approaches to catheter ablation for persistent atrial fibrillation.

BACKGROUND: Catheter ablation is less successful for persistent atrial fibrillation than for paroxysmal atrial fibrillation. Guidelines suggest that adjuvant substrate modification in addition to pulmonary-vein isolation is required in persistent atrial fibrillation. METHODS: We randomly assigned 589 patients with persistent atrial fibrillation in a 1:4:4 ratio to ablation with pulmonary-vein isolation alone (67 patients), pulmonary-vein isolation plus ablation of electrograms showing complex fractionated activity (263 patients), or pulmonary-vein isolation plus additional linear ablation across the left atrial roof and mitral valve isthmus (259 patients). The duration of follow-up was 18 months. The primary end point was freedom from any documented recurrence of atrial fibrillation lasting longer than 30 seconds after a single ablation procedure. RESULTS: Procedure time was significantly shorter for pulmonary-vein isolation alone than for the other two procedures (P<0.001). After 18 months, 59% of patients assigned to pulmonary-vein isolation alone were free from recurrent atrial fibrillation, as compared with 49% of patients assigned to pulmonary-vein isolation plus complex electrogram ablation and 46% of patients assigned to pulmonary-vein isolation plus linear ablation (P=0.15). There were also no significant differences among the three groups for the secondary end points, including freedom from atrial fibrillation after two ablation procedures and freedom from any atrial arrhythmia. Complications included tamponade (three patients), stroke or transient ischemic attack (three patients), and atrioesophageal fistula (one patient). CONCLUSIONS: Among patients with persistent atrial fibrillation, we found no reduction in the rate of recurrent atrial fibrillation when either linear ablation or ablation of complex fractionated electrograms was performed in addition to pulmonary-vein isolation. (Funded by St. Jude Medical; ClinicalTrials.gov number, NCT01203748.).

Frequent Home Monitoring of ICD Is Effective to Prevent Inappropriate Defibrillator Shock Delivery.

Recently, in the context of telemedicine, telemonitoring services are gaining attention. They are offered, for example, to patients with implantable cardioverter defibrillators (ICDs). A major problem associated with ICD therapy is the occurrence of inappropriate shocks which impair patients' quality of life and may also be arrhythmogenic. The telemonitoring can provide a valid support to intensify followup visits, in order to improve the prevention of inappropriate defibrillator shock, thus enhancing patient safety. Inappropriate shock generally depends on atrial fibrillation, supraventricular tachycardia, and abnormal sensing (such as those caused by electromagnetic interferences). As a practical example, an unusual case of an ICD patient who risked an inappropriate shock while taking a shower is reported. Continuous remote telemonitoring was able to timely warn cardiologist via GSM-SMS, who were able to detect improper sensing examining the intracardiac electrogram via Web. Patient was promptly contacted and warned to not further come in contact with the hydraulic system and any electrical appliance to prevent an inappropriate defibrillator shock. This demonstrates the effectiveness and usefulness of continuous remote telemonitoring in supporting ICD patients.

Evaluation and reduction of asymptomatic cerebral embolism in ablation of atrial fibrillation, but high prevalence of chronic silent infarction: results of the evaluation of reduction of asymptomatic cerebral embolism trial.

BACKGROUND: This prospective, multicenter study sought to evaluate the incidence of asymptomatic cerebral emboli (ACE) during ablation of atrial fibrillation (AF) using a multielectrode radiofrequency (MER) system when specific procedural changes were applied. METHODS AND RESULTS: Sixty subjects (age 60±10 years; 87% paroxysmal; CHADS2 score, 0.6±0.7) undergoing AF ablation with a circular MER catheter were studied. Three procedural changes were specified: (1) ablation was performed under therapeutic vitamin K antagonist and heparin to maintain activated clotting time>350 seconds; (2) submerged loading of the catheter into the introducer before sheath insertion to minimize air ingress; and (3) either the distal or proximal electrode of the circular MER catheter was deactivated to prevent inadvertent bipolar radiofrequency interaction. MRI was performed <7 days preablation and 2 days postablation. Subjects with new cerebral findings after ablation underwent repeat MRI after 1 month. An acute ACE lesion was defined by a new hyperintensity on diffusion-weighted and fluid-attenuated inversion recovery cerebral MRI sequences. Neurological function was evaluated at baseline, postablation, and 1 month. All target pulmonary veins were isolated. In 60% (36/60) of patients, pre-existing cerebral lesions were seen on the preprocedure MRI (8 lesions per subject; interquartile range, 3-22). New postprocedural ACE occurred in only 1/60 patients (incidence, 1.7%; 95% confidence interval, 0.04-8.9), which was no longer visible on MRI after 1 month. CONCLUSIONS: Applying procedural changes to MER ablation significantly reduces the ACE incidence to 1.7%, which is on the low end of reported ACE rates of any technology. CLINICAL TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov; Identifier: NCT01520532.

Ablation of paroxysmal and persistent atrial fibrillation with multielectrode phased radiofrequency duty-cycled catheters: long-term results from a large cohort of patients.

BACKGROUND: Catheter ablation is a widely used approach to treat patients with drug refractory paroxysmal atrial fibrillation (PAF) and persistent atrial fibrillation (CAF). The aim of this analysis was to evaluate the long-term safety and efficacy of the multielectrode/phased radiofrequency (RF)/duty-cycled ablation catheters in the treatment of both PAF and CAF in a large cohort of patients. METHODS AND RESULTS: From July 2008 to February 2010, 429 consecutive drug refractory symptomatic patients (mean age 60 ± 12 years old, 58% men, 68% PAF, 32% CAF) were treated. Seventy-five patients had two procedures resulting in a total of 504 procedures (procedure mean time: 62 ± 15 min). Following ablation, 4-day continuous Holter monitoring was done every 3 months. Recurrence was defined as any atrial tachyarrhythmia of more than 30 s. At 3 months 97.4% of patients were off antiarrhythmic drugs. During a mean follow-up of 22 ± 5 months, freedom from AF recurrence was 68.5% (95% CI: 63.8-72.6) and higher for PAF than CAF patients. The risk of AF recurrence in PAF patients increased in the presence of hypertension, dyslipidemia, large left atrial diameter (LAD) and low ejection fraction. For CAF patients, the risk of AF recurrence increased with larger LAD and lower ejection fraction. Complications that resolved prior to discharge were observed in nine patients (2.1%) with no strokes/transient ischemic attacks (TIAs). CONCLUSION: The ablation of symptomatic PAF and CAF with multielectrode phased radiofrequency/duty-cycled ablation catheters shows long-term safety and effectiveness with relatively short procedure times.

C-reactive protein and P-wave in hypertensive patients after conversion of atrial fibrillation.

AIMS: P maximum/P dispersion and high-sensitivity C-reactive protein (hs-C-reactive protein) have been proposed as useful markers for predicting the history and recurrence of atrial fibrillation. We tested the association between hs-C-reactive protein and maximum P-wave duration (P maximum)/P-wave dispersion (P dispersion) in hypertensive patients after conversion of atrial fibrillation. METHODS: We enrolled 92 patients. Hs-C-reactive protein was assessed before cardioversion, the 12-lead ECG was recorded immediately after sinus rhythm restoration. RESULTS: At univariate analysis P maximum above 120  ms was associated with male sex (P = 0.0009), body mass index at least 25  kg/m (P = 0.03) and hs-C-reactive protein greater than 0.30  mg/dl (P = 0.0001), and left atrium diameter greater than 40 mm nearly significant (P = 0.05). P dispersion above 40  ms was associated with hs-C-reactive protein greater than 0.30  mg/dl (P = 0.0001) and left atrium diameter greater than 0.40  mm (P = 0.03). P maximum/P dispersion (mean ±â€ŠSD) was significantly longer in patients with hs-C-reactive protein greater than 0.30  mg/dl compared to patients with hs-C-reactive protein 0.30  mg/dl or less (P = 0.0001 for both). At multivariate analysis P maximum above 120  ms was associated with male sex (P = 0.01) and with hs-C-reactive protein greater than 0.30  mg/dl (P = 0.002), whereas P dispersion above 40  ms was associated only with hs-C-reactive protein greater than 0.30  mg/dl (P = 0.0006). CONCLUSION: Male sex and hs-C-reactive protein were associated with P maximum above 120  ms; hs-C-reactive protein was also associated with P dispersion above 40  ms in hypertensive patients after conversion of atrial fibrillation. Subclinical inflammation may be associated with delayed/inhomogeneous atrial activation in hypertensive patients affected by atrial fibrillation.

Baseline apnoea/hypopnoea index and high-sensitivity C-reactive protein for the risk of recurrence of atrial fibrillation after successful electrical cardioversion: a predictive model based upon the multiple effects of significant variables.

AIMS: We tested apnoea/hypopnoea index (AHI), high-sensitivity (hs) C-reactive protein and clinical/instrumental variables as predictors of atrial fibrillation (AF) recurrence over 1-year follow-up after successful electrical cardioversion. METHODS AND RESULTS: We enrolled 158 consecutive patients. Apnoea/hypopnoea index was assessed with standard overnight polysomnography and hs-C-reactive protein with immunonephelometry assay the day before electrical cardioversion. Atrial fibrillation recurrences occurred in 81 patients (51%). Predictors at univariate analysis were: AHI > or = 15 events/h (P = 0.001), hs-C-reactive protein >0.30 mg/dL (P = 0.009), AF duration >3 days (P = 0.008), diabetes (P = 0.03), and ongoing anti-arrhythmic therapy at the time of electrical cardioversion (P = 0.03). Survival analysis confirmed that patients with AHI > or = 15 events/h and hs-C-reactive protein > 0.30 mg/dL had a higher recurrence rate of AF (log rank P = 0.0006 and P = 0.01, respectively). Predictors at multivariate analysis were: AHI > or = 15 events/h (P = 0.003), hs-C-reactive protein > 0.30 mg/dL (P = 0.01) and ongoing anti-arrhythmic therapy (P = 0.04). A predictive model based upon the multiple effects of significant variables plus age as a continuous variable stratified the risk of AF recurrence, more than tripled with all dichotomized variables altered with respect to normal variables (85 vs. 27%). CONCLUSION: AHI > or = 15 events/h and hs-C-reactive protein > 0.30 mg/dL are the strongest predictors of the predictors chosen of AF recurrence after successful electrical cardioversion over 1-year follow-up.

Serologic response to hepatitis B vaccine with high dose and increasing number of injections in HIV infected adult patients.

Sixty-five HIV-infected patients received high-dose (40mug), short interval HBV vaccine. In non-responders to the initial immunization, 1-3 boosters were administered. Rate of response was 60.0% after primary vaccination, and 89.2% after boosters. However, 12 and 24 months after the last vaccination, only 63% and 32.7% of the responders, respectively, had persistence of protective anti-HBs titers (> or =10 IU/L). The results of logistic regression show that gender, CD4 count, and HIV viral load were significant predictors of vaccination outcome. This study suggests that in HIV-infected patients with relatively high CD4 count, response to high dose of HBV vaccine is suboptimal. Rate of response may be increased by vaccine boosts, but antibody titers are significantly lower in non-responders than in responders to primary vaccination. Since persistence of anti-HBs titers appears significantly related to antibody titers after the immunization procedure, monitoring of anti-HBs, particularly in patients with low level of protective antibody titers after primary vaccination or boosters, seems more than justified.

Radiofrequency catheter ablation of atrial fibrillation in athletes referred for disabling symptoms preventing usual training schedule and sport competition.

INTRODUCTION: Atrial fibrillation (AF) may occasionally affect athletes by impairing their ability to compete, and leading to noneligibility at prequalification screening. The impact of catheter ablation (CA) in restoring full competitive activity of athletes affected by AF is not known. The aim of our study was to investigate the effectiveness of CA of idiopathic AF in athletes with palpitations impairing physical performance and compromising eligibility for competitive activities. METHODS AND RESULTS: Twenty consecutive competitive athletes (all males; 44.4 +/- 13.0 years) with disabling palpitations on the basis of idiopathic drug-refractory AF underwent 46 procedures (2.3 +/- 0.4 per patient) according to a prospectively designed multiprocedural CA approach that consolidates pulmonary veins (PV) isolation through subsequent steps. Preablation, effort-induced AF could be documented in 13 patients (65%) during stress ECG and significantly reduced maximal effort capacity (176 +/- 21 W), as compared with patients with no AF during effort (207 +/- 43 W, P < 0.05). At the end of CA protocol, which also included ablation of atrial flutter (AFL) in 7 patients, 18 (90.0%) patients were free of AF and two (10.0%) reported short-lasting (minutes) episodes of palpitations during 36.1 +/- 12.7 months follow-up. Compared with preablation, postablation maximal exercise capacity significantly improved (from 183 +/- 32 to 218 +/- 20 W, P < 0.02). All baseline quality of life (QoL) parameters pertinent to physical activity significantly improved (P < 0.05) at the end of CA protocol. All athletes obtained reeligibility and could effectively reinitiate sport activity. CONCLUSIONS: AF, alone or in combination with AFL, may significantly impair maximal effort capacity thereby limiting competitive performance. Multiple PV isolation proved very effective in these patients to restore full competitive activity and allow reeligibility.