Lack of early etiologic investigations in young sudden cardiac death.

BACKGROUND: Since majority of sudden cardiac arrest (SCA) victims die in the intensive care unit (ICU), early etiologic investigations may improve understanding of SCA and targeted prevention. METHODS: In this prospective, population-based registry all SCA admitted alive across the 48 hospitals of the Paris area were enrolled. We investigated the extent of early etiologic work-up among young SCD cases (<45 years) eventually dying within the ICU. RESULTS: From May 2011 to May 2018, 4,314 SCA patients were admitted alive. Among them, 3,044 died in ICU, including 484 (15.9%) young patients. SCA etiology was established in 233 (48.1%) and remained unexplained in 251 (51.9%). Among unexplained (compared to explained) cases, coronary angiography (17.9 vs. 49.4%, P < 0.001), computed tomography scan (24.7 vs. 46.8%, P < 0.001) and trans-thoracic echocardiography (31.1 vs. 56.7%, P < 0.001) were less frequently performed. Only 22 (8.8%) patients with unexplained SCD underwent all three investigations. SCDs with unexplained status decreased significantly over the 7 years of the study period (from 62.9 to 35.2%, P = 0.005). While specialized TTE and CT scan performances have increased significantly, performance of early coronary angiography did not change. Autopsy, genetic analysis and family screening were performed in only 48 (9.9%), 5 (1.0%) and 14 cases (2.9%) respectively. CONCLUSIONS: More than half of young SCD dying in ICU remained etiologically unexplained; this was associated with a lack of early investigations. Improving early diagnosis may enhance both SCA understanding and prevention, including for relatives. Failure to identify familial conditions may result in other preventable deaths within these families.

FRAGILE: FRench Attitude reGistry in case of ICD LEad replacement.

AIMS: FRench Attitude reGistry in case of ICD LEad replacement (FRAGILE) registry was set-up to describe the attitude in different French institutions in case of implantable cardioverter-defibrillator (ICD) lead replacement, extraction, or abandonment and to compare outcomes in both groups. METHODS AND RESULTS: Prospective observational study comparing two attitudes in case of ICD lead replacement, extraction, or abandonment. Primary endpoint describes the attitude in different French centres, collect parameters that may influence the decision. Secondary endpoint compares early and mid-term (2 years) complications in both groups.Between April 2013 and April 2017, 552 patients were included in 32 centres. 434 (78.6%) were male, mean patient's age was 60.3 ± 14.4 years. In 56.9% of the cases, the decision was to explant the lead. Patients in the extraction group were younger than in the abandonment group (56.7 ± 14.5 vs. 65 ± 12.7 P < 0.0001) and less likely to have comorbidities (46.5% vs. 58.3% of the patients P = 0.022). The mean lead dwelling time was significantly longer in the abandonment group as compared with the extraction group (7.6 ± 3.9 vs. 5.2 ± 3.1 years, P < 0.0001). There was no statistical difference between both groups concerning early and 2 years complications. CONCLUSION: In this registry, the strategy in case of non-infected ICD lead replacement was mainly influenced by patient's age and comorbidities and lead dwelling time. No difference was observed in outcomes in both strategies.

Subcutaneous Implantable Cardioverter-Defibrillator Lead Extraction: First Multicenter French Experience.

OBJECTIVES: The aim of this multicenter study was to characterize the efficacy and safety of subcutaneous implantable cardioverter-defibrillators (S-ICDs) lead extraction procedures. BACKGROUND: S-ICDs have been developed to limit lead-related complications inherent to transvenous ICD devices. To date, no study has specifically investigated the safety and feasibility of S-ICD lead extraction procedures. METHODS: Patients requiring S-ICD lead extraction between February 1, 2014, and February 28, 2019, were retrospectively included in 10 centers. The primary endpoint of the study was procedural success, defined as the removal of all the lead and lead material from the subcutaneous space. Secondary endpoints included procedural complications and the need for specific extraction tools. RESULTS: S-ICD lead extraction procedures were performed in 32 patients (mean age 45.7 ± 13.8 years, 75.0% men, 65.6% in primary prevention). The median time from S-ICD lead implantation was 9.3 months (5.4 to 17.5 months). The primary endpoint, that is, complete removal of the material, was achieved in 96.9% of the patients, and only 1 procedural failure occurred (3.1%). Simple traction of the S-ICD lead was successful in 19 patients (59.4%), whereas 3 patients (9.4%) needed an additional incision and 9 patients (28.1%) required mechanical sheath to remove lead adhesions around the coil. No procedure-related complications occurred. Patients with successful simple traction extraction were implanted more recently (7.1 months [2.8 to 12.2 months] vs. 16.5 months [7.5 to 20.8 months]; p = 0.04) and had less prior history of sternotomy (2 [10.5%] vs. 5 [38.5%] patients; p = 0.09). CONCLUSIONS: S-ICD lead extraction is an efficient and safe procedure, but may require some specific tools like mechanical sheath, specifically when fibrotic adhesions developed around the parasternal coil.

Use of a radiofrequency guidewire to simplify workflow for left atrium access: a case series.

PURPOSE: Transseptal puncture (TSP) is widely used in catheter-based cardiac procedures to gain left atrial access, but its workflow has remained largely unchanged in the last 50 years. This study evaluated the safety and efficacy of a novel, simplified technique for TSP with a radiofrequency (RF)-powered guidewire that eliminates multiple exchanges required with standard needles. METHODS: TSP was performed in 84 patients undergoing left-sided procedures (72 atrial fibrillation ablations [32 RF, 40 cryoballoon], 4 atrial tachycardia ablations, 2 ventricular arrhythmia ablations, 6 left atrial appendage closure) utilizing a stiff, exchange length RF guidewire. Under fluoroscopic and echocardiographic guidance, the RF guidewire was used to facilitate septal puncture with RF energy and provide a rail for advancing catheters to the left atrium without exchange. All procedures were performed under general anesthesia or sedation. RESULTS: TSP was achieved in all patients with no complications. The RF guidewire allowed catheters to be tracked back up to the superior vena cava without exchange in cases where another dropdown was desired to locate a preferred puncture site. The stiffness of the wire provided adequate support to advance all sheaths to the left side regardless of outer diameter. CONCLUSION: TSP was performed safely and successfully for various left heart procedures with a RF guidewire that served as an RF transseptal device and a stiff guidewire. This allowed for a more efficient and potentially safer technique without the need for re-wiring or an over the wire sheath exchange. This provides substantial savings in both time and materials.

Position paper concerning the competence, performance and environment required in the practice of complex ablation procedures.

The introduction of catheter ablation techniques has vastly improved the treatment of cardiac arrhythmias. However, as complex ablations are technically demanding and can cause various complications, they require a high level of expertise to maximize success rates and minimize complication rates. As French recommendations regarding the required technical competence and equipment are not yet available, this position paper has been compiled by the Working Group of Pacing and Electrophysiology of the French Society of Cardiology, detailing the required features of an interventional cardiac electrophysiological centre for complex ablation procedures: (1) sufficient institutional volume; (2) physician training, qualifications and experience; (3) paramedical staff training and attendance; and (4) institutional facilities and technical equipment. The importance of being able to diagnose, monitor and manage complications associated with complex ablations is highlighted. Supplemental hospital-based resources are also discussed, such as anaesthesia, surgical back-up, intensive care, haemodynamic assistance and imaging. Further, the ideal features of an interventional cardiac electrophysiology training centre are considered. Lastly, the need for quality evaluations and national registries for complex ablations is discussed.

Characteristics and clinical assessment of unexplained sudden cardiac arrest in the real-world setting: focus on idiopathic ventricular fibrillation.

Aims: Recent studies have shown that in more than half of apparently unexplained sudden cardiac arrests (SCA), a specific aetiology can be unmasked by a careful evaluation. The characteristics and the extent to which such cases undergo a systematic thorough investigation in real-life practice are unknown. Methods and results: Data were analysed from an ongoing study, collecting all cases of out-of-hospital cardiac arrest in Paris area. Investigations performed during the index hospitalization or planned after discharge were gathered to evaluate the completeness of assessment of unexplained SCA. Between 2011 and 2016, among the 18 622 out-of-hospital cardiac arrests, 717 survivors (at hospital discharge) fulfilled the definition of cardiac SCA. Of those, 88 (12.3%) remained unexplained after electrocardiogram, echocardiography, and coronary angiography. Cardiac magnetic resonance imaging yielded the diagnosis in 25 (3.5%) cases, other investigations accounted for 14 (2.4%) additional diagnoses, and 49 (6.8%) patients were labelled as idiopathic ventricular fibrillation (IVF) (48.7 ± 15 years, 69.4% male). Among those labelled IVF, only 8 (16.3%) cases benefited from a complete workup (including pharmacological testing). Younger patients [odds ratio (OR) 6.00, 95% confidence interval (CI) 1.80-22.26] and those admitted to university centres (OR 3.60, 95% CI 1.12-12.45) were more thoroughly investigated. Genetic testing and family screening were initiated in only 9 (18.4%) and 12 (24.5%) cases, respectively. Conclusion: Our findings suggest that complete investigations are carried out in a very low proportion of unexplained SCA. Standardized, systematic approaches need to be implemented to ensure that opportunities for specific therapies and preventive strategies (including relatives) are not missed.

Position paper for management of elderly patients with pacemakers and implantable cardiac defibrillators Groupe de rythmologie et stimulation cardiaque de la Société française de cardiologie et Société française de gériatrie et gérontologie.

Despite the increasingly high rate of implantation of pacemakers (PM) and cardioverter-defibrillators (ICD) in elderly patients, data supporting their clinical and cost-effectiveness in this age stratum are ambiguous and contradictory. We reviewed the data regarding the applicability, safety, and effectiveness of the conventional pacing, ICD and cardiac resynchronization therapy (CRT) in elderly patients. Although peri-procedural risk may be slightly higher in the elderly, the procedure of implantation of PMs and ICDs is still relatively safe in this age group. In older patients with sinus node disease, a general consensus is that dual chamber pacing, along with the programming of an algorithm to minimise ventricular pacing is preferred. In very old patients presenting with intermittent or suspected AV block, VVI pacing may be appropriate. In terms of correcting potentially life-threatening arrhythmias, the effectiveness of ICD therapy is comparable in older and younger individuals. However, the assumption of persistent ICD benefit in the elderly population is questionable, as any advantage of the device on arrhythmic death may be attenuated by a higher total non-arrhythmic mortality. While septuagenarians and octogenarians have higher annual all-cause mortality rates, ICD therapy may remain effective in selected patients at high risk of arrhythmic death and with minimum comorbidities despite advanced age. ICD implantation among the elderly, as a group, may not be cost-effective, but the procedure may reach cost-effectiveness in those expected to live >5-7 years after implantation. The elderly patients usually experience a significant functional improvement after CRT, similar to that observed in middle-aged patients. Management of CRT non responders remains globally the same, while considering a less aggressive approach in terms of re interventions (revision of LV lead placement, addition of a RV or LV lead, LV endocardial pacing configuration). Overall, age, comorbidities and comprehensive geriatric assessment should be the decisive factor in making a decision on device implantation selection for survival and well-being benefit in elderly patients.

Position paper for management of elderly patients with pacemakers and implantable cardiac defibrillators: Groupe de Rythmologie et Stimulation Cardiaque de la Société Française de Cardiologie and Société Française de Gériatrie et Gérontologie.

Despite the increasingly high rate of implantation of pacemakers (PMs) and implantable cardioverter defibrillators (ICDs) in elderly patients, data supporting their clinical and cost-effectiveness in this age stratum are ambiguous and contradictory. We reviewed the data regarding the applicability, safety and effectiveness of conventional pacing, ICDs and cardiac resynchronization therapy (CRT) in elderly patients. Although periprocedural risk may be slightly higher in the elderly, the implantation procedure for PMs and ICDs is still relatively safe in this age group. In older patients with sinus node disease, the general consensus is that DDD pacing with the programming of an algorithm to minimize ventricular pacing is preferred. In very old patients presenting with intermittent or suspected atrioventricular block, VVI pacing may be appropriate. In terms of correcting potentially life-threatening arrhythmias, the effectiveness of ICD therapy is similar in older and younger individuals. However, the assumption of persistent ICD benefit in the elderly population is questionable, as any advantageous effect of the device on arrhythmic death may be attenuated by higher total non-arrhythmic mortality. While septuagenarians and octogenarians have higher annual all-cause mortality rates, ICD therapy may remain effective in selected patients at high risk of arrhythmic death and with minimum comorbidities despite advanced age. ICD implantation among the elderly, as a group, may not be cost-effective, but the procedure may reach cost-effectiveness in those expected to live more than 5-7years after implantation. Elderly patients usually experience significant functional improvement after CRT, similar to that observed in middle-aged patients. Management of CRT non-responders remains globally the same, while considering a less aggressive approach in terms of reinterventions (revision of left ventricular [LV] lead placement, addition of a right ventricular or LV lead, LV endocardial pacing configuration). Overall, physiological age, general status and comorbidities rather than chronological age per se should be the decisive factors in making a decision about device implantation selection for survival and well-being benefit in elderly patients.

Safety, feasibility, and outcome results of cardiac resynchronization with triple-site ventricular stimulation compared to conventional cardiac resynchronization.

BACKGROUND: The nonresponder rate to cardiac resynchronization therapy (CRT) may be due to incomplete resynchronization, with dyssynchrony persisting in approximately 30% of patients. We hypothesized that CRT with triple-site ventricular stimulation (TRIV) may improve resynchronization and its outcomes. OBJECTIVE: The purpose of this study was to assess the feasibility and safety of TRIV and collected data on clinical outcomes to dimension future studies. METHODS: Our pilot randomized trial was designed to assess the safety and feasibility of TRIV with 2 right ventricular leads and 1 left ventricular leads compared to conventional CRT. The primary end-point was the rate of severe adverse events at 6 months. Secondary end-points included functional improvement parameters, quality-of-life (QOL) score, and changes of echocardiographic indices at 6 and 12 months in a subset of patients. RESULTS: Seventy-six patients were enrolled at 11 centers and randomized to control or TRIV arm. All implant procedures but one were successful. At 6 months, there was no statistical difference between proportions of patients with at least 1 severe adverse event in both groups (34.1% vs 25.7%, P = .425). There also was no difference between functional improvement parameters, 6-minute walking distances (P = .40), QOL scores (P = .27), and echographic indices. At 12 months, the proportions of patients with a left ventricular ejection fraction gain of more than 5%, 10%, or 15% were significantly superior with TRIV. CONCLUSION: TRIV pacing is an effective and safe technique and may provide a greater benefit in ventricular remodeling than conventional CRT. Further studies are needed to assess its long-term benefit.

Comparison between B·R·A·H·M·S PCT direct, a new sensitive point-of-care testing device for rapid quantification of procalcitonin in emergency department patients and established reference methods - a prospective multinational trial.

BACKGROUND: Procalcitonin (PCT) is increasingly being used for the diagnostic and prognostic work up of patients with suspected infections in the emergency department (ED). Recently, B·R·A·H·M·S PCT direct, the first high sensitive point-of-care test (POCT), has been developed for fast PCT measurement on capillary or venous blood samples. METHODS: This is a prospective, international comparison study conducted in three European EDs. Consecutive patients with suspicion of bacterial infection were included. Duplicate determination of PCT was performed in capillary (fingertip) and venous whole blood (EDTA), and compared to the reference method. The diagnostic accuracy was evaluated by correlation and concordance analyses. RESULTS: Three hundred and three patients were included over a 6-month period (60.4% male, median age 65.2 years). The correlation between capillary or venous whole blood and the reference method was excellent: r2=0.96 and 0.97, sensitivity 88.1% and 93.0%, specificity 96.5% and 96.8%, concordance 93% and 95%, respectively at a 0.25 µg/L threshold. No significant bias was observed (-0.04 and -0.02 for capillary and venous whole blood) although there were 6.8% and 5.1% outliers, respectively. B·R·A·H·M·S PCT direct had a shorter time to result as compared to the reference method (25 vs. 144 min, difference 119 min, 95% CI 110-134 min, p<0.0001). CONCLUSIONS: This study found a high diagnostic accuracy and a faster time to result of B·R·A·H·M·S PCT direct in the ED setting, allowing shortening time to therapy and a more wide-spread use of PCT.

Comparison between radiofrequency with contact force-sensing and second-generation cryoballoon for paroxysmal atrial fibrillation catheter ablation: a multicentre European evaluation.

AIMS: Whether pulmonary vein isolation (PVI) for paroxysmal atrial fibrillation (PAF) using contact force (CF)-guided radiofrequency (RF) or second-generation cryoballoon (CB) present similar efficacy and safety remains uncertain. METHODS AND RESULTS: We performed a multicentre study comparing procedural safety and arrhythmia recurrence after standardized PVI catheter ablation for PAF using CF-guided RF ablation (Thermocool(®) SmartTouch™, Biosense Webster; or Tacticath™, St Jude Medical) (CF group) with second-generation CB ablation (Arctic Front Advance™, Medtronic) (CB group). Overall, 376 patients (mean age 59.8 ± 10.4 years, 280 males) were enrolled in 4 centres: 198 in CF group and 178 in CB group. Procedure was shorter for CB group than for CF group (109.6 ± 40 vs. 122.5 ± 40.7 min, P = 0.003), but fluoroscopy duration and X-ray exposure were not statistically different (P = 0.1 and P = 0.22, respectively). Overall complication rate was similar in both groups: 14 (7.1%) in the CF group vs. 13 (7.3%) in the CB group (P = 0.93). However, transient right phrenic nerve palsy occurred only in CB group (10 patients, 5.6%; P = 0.001 vs. CF group) and severe non-lethal complications (embolic event, tamponade, or oesophageal injury) occurred only in CF group (5 patients, 2.5%; P = 0.03 vs. CB group). No periprocedural death occurred in either group. Single-procedure freedom from any atrial arrhythmias at 18 months post-ablation was comparable in CF group and CB group (76 vs. 73.3%, respectively, log rank P = 0.63). CONCLUSION: Pulmonary vein isolation using CF-guided RF and second-generation CB leads to comparable single-procedure arrhythmia-free survival at up to 18 months with similar overall complication rate.

Comparison of a radiofrequency powered flexible needle with a classic rigid Brockenbrough needle for transseptal punctures in terms of safety and efficacy.

INTRODUCTION: This study aimed to evaluate the safety and efficacy of utilising an innovative radiofrequency (RF) powered flexible needle to achieve transseptal puncture (TSP). METHODS AND RESULTS: A RF powered flexible needle (Toronto catheter, Baylis Medical Company Inc.) associated with a stiffer dilator (Torflex Superstrong, Baylis Medical Company Inc.) was used in 125 consecutive patients referred for left sided ablations (mean age=55.6, male=86.5%) and compared with a standard transseptal set (BRK needle, SL0 sheath and dilator, St Jude Medical, Inc.) used in the previous 100 patients (mean age=56, male 82%). TSP was achieved in 95/100 patients in the Brockenbrough group and in all 125 patients in the Toronto group (p=0.01) despite an equivalent proportion of difficult situations (8 and 9% respectively) and patients with a prior TSP (17% vs 24%). 7/100 needle related events (failure, aborted attempt or pericardial effusion) occurred in the Brockenbrough group and none in the Toronto group (p=0.01). The Toronto needle crossed the septum at the first attempt in 123/125 (98.4%) patients and the Brockenbrough needle in 84/95 (88%) patients (p<0.001). CONCLUSION: Our data suggest that the Toronto RF powered flexible needle is safer and more efficient than a standard Brockenbrough needle and can be used not only in difficult situations but routinely to achieve TSP.

Addition of a second LV pacing site in CRT nonresponders rationale and design of the multicenter randomized V(3) trial.

BACKGROUND: Cardiac resynchronization therapy (CRT) is an effective treatment of heart failure (HF) in presence of a depressed left ventricular (LV) ejection fraction and a wide QRS complex. It is limited by a high proportion of nonresponders. Attempts have been made, in small studies, to increase the number of stimulation sites to optimize the resynchronization therapy. V(3) is a planned multicenter, randomized trial whose objective is to evaluate the clinical benefit conferred by the addition of a second LV lead in nonresponders after at least 6 months of standard biventricular stimulation. METHODS AND RESULTS: A total of 84 patients will be enrolled in 11 French medical centers. Patients will be randomly assigned to receive either an additional LV lead (test group) or to keep their current stimulation system unchanged (control group). Enrollment is planned to begin in March 2010 and is expected to end within 1 year. The primary study end point will be the HF clinical composite score evaluated at 1 year follow-up. Secondary end points include degree of echocardiographic reverse remodeling and changes in clinical measurements. CONCLUSIONS: The V(3) trial will examine the clinical benefit conferred by the addition of a second LV lead in nonresponders to standard CRT.

Method for the selective measurement of amino-terminal variants of procalcitonin.

BACKGROUND: Procalcitonin (PCT) is an established marker for diagnosing and monitoring bacterial infections. Full-length PCT [116 amino acids that make up procalcitonin (PCT1-116)] can be truncated, leading to des-Ala-Pro-PCT (des-Alanin-Prolin-Procalcitonin; PCT3-116). Current immunoassays for PCT ("total PCT") use antibodies directed against internal epitopes and are unable to distinguish amino-terminal PCT variants. Here we describe the development of monoclonal antibodies recognizing the amino-termini of PCT1-116 and PCT3-116 and their use in the selective measurement of these PCT species. METHODS: With newly developed monoclonal antibodies against the amino-termini of PCT1-116 and PCT3-116, and an antibody against the katacalcin moiety of PCT, we developed and characterized immunoluminometric assays for the 2 PCT peptides. We comparatively assessed the kinetics of PCT variants in a human endotoxemia model. RESULTS: Monoclonal antibodies against the amino-termini of PCT1-116 and PCT3-116 showed <1% cross-reactivity with other PCT-related peptides. The sandwich assays for PCT1-116 and PCT3-116 had functional assay sensitivities of 5 and 1.2 pmol/L, respectively, and exhibited recoveries within 20% of expected values. Plasma PCT1-116 was stable for 6 h at 22 degrees C and 24 h at 4 degrees C, and PCT3-116 was stable for at least 24 h at both temperatures. During experimental endotoxemia in healthy people, both PCT1-116 and PCT3-116 increased early in parallel with total PCT, but further increases in PCT1-116 were significantly slower than for PCT3-116 (P = 0.0049) and total PCT (P = 0.0024). CONCLUSIONS: The new assays selectively measure PCT1-116 and PCT3-116. Both PCT species increase early during endotoxemia but differ in their kinetics thereafter. The selective measurement of PCT species with different in vivo kinetics may be useful in improving PCT-guided therapies.

New assay for the measurement of selenoprotein P as a sepsis biomarker from serum.

Selenium (Se) is incorporated into selenoproteins as the 21st proteinogenic amino acid selenocysteine. Serum Se concentrations decline during critical illness and are indicative of poor prognosis. Serum Se is mainly contained in the hepatically derived selenoprotein P (SePP) which controls the expression of antioxidative selenoproteins. Here, we describe the development of an immunoluminometric sandwich assay that uses two polyclonal sheep antihuman SePP antibodies. After assessing the stability of the analyte, we determined SePP concentrations in samples from healthy individuals and patients with sepsis. The analytical detection limit was 0.016 mg SePP/L serum. The assay was linear on dilution. SePP was stable in serum at room temperature for at least 24 h and resistant to six freeze-thaw cycles. Median SePP concentration in healthy individuals was 3.04 mg SePP/L serum (25th-75th percentiles, 2.6-3.4 mg/L) which corresponded to 98.4 microg Se/L serum. The interlaboratory CV was <20% for SePP values >0.06 mg/L. There was no association with gender, but concentrations differed between young and older individuals. Median SePP concentrations were significantly (P<0.0001) decreased in patients with sepsis (n=60) compared to healthy controls (n=318). Since SePP contains the major fraction of serum Se, we conclude that downregulation of SePP biosynthesis or removal of circulating SePP from blood underlies the negative acute phase response of serum Se in critical illness.