Left atrial remodeling and voltage-guided ablation outcome in persistent atrial fibrillation patients according to CHA2DS2-VASc score.

BACKGROUND: CHA2DS2-VASc score-related differences have been reported in atrial fibrotic remodeling and prognosis of atrial fibrillation (AF) patients after ablation. There are currently no data on the efficacy of low voltage zone (LVZ)-guided ablation in persistent AF patients according to CHA2DS2-VASc score. We assessed in a cohort of persistent AF patients the extent of LVZ, the regional distribution of LA voltage and the outcome of LA voltage-guided substrate ablation in addition to PVI according to CHA2DS2-VASc score. METHODS: 138 consecutive persistent AF patients undergoing a first voltage-guided catheter ablation were enrolled. 58 patients with CHAD2DS2-VASc score ≥ 3 and 80 patients with CHAD2DS2-VASc score ≤ 2 were included. LA voltage maps were obtained using 3D-electroanatomical mapping system in sinus rhythm. LVZ was defined as < 0.5 mV. RESULTS: In the high CHAD2DS2-VASc score group, LA voltage was lower (1.5 [1.1-2.5] vs. 2.3 [1.5-2.8] mV, p = 0.02) and LVZs were more frequently identified (40% vs. 18%), p < 0.01). Female with CHA2DS2-VASc score ≥ 3 (p = 0.031), LA indexed volume (p = 0.009) and P-wave duration ≥ 150 ms (p = 0.001) were predictors of LVZ. After a 36-month follow-up, atrial arrhythmia-free survival was similar between the two groups (logrank test, P = 0.676). CONCLUSIONS: AF patients with CHAD2DS2-VASc score ≥ 3 display more LA substrate remodeling with lower voltage and more LVZs compared with those with CHAD2DS2-VASc score ≤ 2. Despite this atrial remodeling, they had similar and favorable 36 months results after one single procedure. Unlike male with CHAD2DS2-VASc score ≥ 3, female with CHAD2DS2-VASc score ≥ 3 was predictor of LVZ occurrence.

Robustness and relevance of predictive score in sudden cardiac death for patients with Brugada syndrome.

AIMS: Risk stratification of sudden cardiac arrest (SCA) in Brugada syndrome (Brs) remains the main challenge for physicians. Several scores have been suggested to improve risk stratification but never replicated. We aim to investigate the accuracy of the Brs risk scores. METHODS AND RESULTS: A total of 1613 patients [mean age 45 ± 15 years, 69% male, 323 (20%) symptomatic] were prospectively enrolled from 1993 to 2016 in a multicentric database. All data described in the risk score were double reviewed for the study. Among them, all patients were evaluated with Shanghai score and 461 (29%) with Sieira score. After a mean follow-up of 6.5 ± 4.7 years, an arrhythmic event occurred in 75 (5%) patients including 16 SCA, 11 symptomatic ventricular arrhythmia, and 48 appropriate therapies. Predictive capacity of the Shanghai score (n = 1613) and the Sieira (n = 461) score was, respectively, estimated by an area under the curve of 0.73 (0.67-0.79) and 0.71 (0.61-0.81). Considering Sieira score, the event rate at 10 years was significantly higher with a score of 5 (26.4%) than with a score of 0 (0.9%) or 1 (1.1%) (P < 0.01). No statistical difference was found in intermediate-risk patients (score 2-4). The Shanghai score does not allow to better stratify the risk of SCA. CONCLUSIONS: In the largest cohort of Brs patient ever described, risk scores do not allow stratifying the risk of arrhythmic event in intermediate-risk patient.

Angiotensin II-induced upregulation of SGLT1 and 2 contributes to human microparticle-stimulated endothelial senescence and dysfunction: protective effect of gliflozins.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduced cardiovascular risk in type 2 diabetes patients independently of glycemic control. Although angiotensin II (Ang II) and blood-derived microparticles are major mediators of cardiovascular disease, their impact on SGLT1 and 2 expression and function in endothelial cells (ECs) and isolated arteries remains unclear. METHODS: ECs were isolated from porcine coronary arteries, and arterial segments from rats. The protein expression level was assessed by Western blot analysis and immunofluorescence staining, mRNA levels by RT-PCR, oxidative stress using dihydroethidium, nitric oxide using DAF-FM diacetate, senescence by senescence-associated beta-galactosidase activity, and platelet aggregation by aggregometer. Microparticles were collected from blood of patients with coronary artery disease (CAD-MPs). RESULTS: Ang II up-regulated SGLT1 and 2 protein levels in ECs, and caused a sustained extracellular glucose- and Na+-dependent pro-oxidant response that was inhibited by the NADPH oxidase inhibitor VAS-2780, the AT1R antagonist losartan, sotagliflozin (Sota, SGLT1 and SGLT2 inhibitor), and empagliflozin (Empa, SGLT2 inhibitor). Ang II increased senescence-associated beta-galactosidase activity and markers, VCAM-1, MCP-1, tissue factor, ACE, and AT1R, and down-regulated eNOS and NO formation, which were inhibited by Sota and Empa. Increased SGLT1 and SGLT2 protein levels were observed in the rat aortic arch, and Ang II- and eNOS inhibitor-treated thoracic aorta segments, and were associated with enhanced levels of oxidative stress and prevented by VAS-2780, losartan, Sota and Empa. CAD-MPs promoted increased levels of SGLT1, SGLT2 and VCAM-1, and decreased eNOS and NO formation in ECs, which were inhibited by VAS-2780, losartan, Sota and Empa. CONCLUSIONS: Ang II up-regulates SGLT1 and 2 protein expression in ECs and arterial segments to promote sustained oxidative stress, senescence and dysfunction. Such a sequence contributes to CAD-MPs-induced endothelial dysfunction. Since AT1R/NADPH oxidase/SGLT1 and 2 pathways promote endothelial dysfunction, inhibition of SGLT1 and/or 2 appears as an attractive strategy to enhance the protective endothelial function.

Incomplete Recovery From Takotsubo Syndrome Is a Major Determinant of Cardiovascular Mortality.

BACKGROUND: Although there is an apparent rapid and spontaneous recovery of left ventricular ejection fraction (LVEF) in patients with Takotsubo syndrome (TTS), recent studies have demonstrated a long-lasting functional impairment in those patients. The present study sought to evaluate the predictors of incomplete recovery following TTS and its impact on cardiovascular mortality.Methods and Results:Patients with TTS between 2008 and 2018 were retrospectively enrolled at 3 different institutions. After exclusion of in-hospital deaths, 407 patients were split into 2 subgroups according to whether their LVEF was >50% (recovery group; n=341), or ≤50% (incomplete recovery group; n=66) at the chronic phase. Multivariate logistic regression analysis found that LVEF (odds ratio [OR]: 0.94; 95% confidence interval [CI]: 0.91-0.98; P<0.001) and C-reactive protein levels (OR: 1.11; 95% CI: 1.02-1.22; P=0.02) at discharge were independent predictors of incomplete recovery. At a median follow up of 52 days, a higher cardiovascular mortality was evident in the incomplete recovery group (16% vs. 0.6%; P<0.001). CONCLUSIONS: This study demonstrated that incomplete recovery after TTS is characterized by residual systemic inflammation and an increased cardiac mortality at follow up. Altogether, the present study findings determined that patients with persistent inflammation are a high-risk subgroup, and should be targeted in future clinical trials with specific therapies to attenuate inflammation.

Clinical features of patients with acute coronary syndrome during the COVID-19 pandemic.

Although a reduction in hospital admissions of acute coronary syndromes (ACS) patients has been observed globally during the coronavirus disease 2019 (COVID-19) pandemic, clinical features of those patients have not been fully investigated. The aim of the present analysis is to investigate the incidence, clinical presentation, and outcomes of patients with ACS during the COVID-19 pandemic. We performed a retrospective analysis of consecutive patients who were admitted for ACS at our institution between March 1 and April 20, 2020 and compared with the equivalent period in 2019. Admissions for acute myocardial infarction (AMI) reduced by 39.5% in 2020 compared with the equivalent period in 2019. Owing to the emergency medical services (EMS) of our region, all time components of ST-elevated myocardial infarction care were similar during the COVID-19 outbreak as compared with the previous year's dataset. Among the 106 ACS patients in 2020, 7 patients tested positive for COVID-19. Higher incidence of type 2 myocardial infarction (29% vs. 4%, p = 0.0497) and elevated D-dimer levels (5650 µg/l [interquartile range (IQR) 1905-13,625 µg/l] vs. 400 µg/l [IQR 270-1050 µg/l], p = 0.02) were observed in COVID-19 patients. In sum, a significant reduction in admission for AMI was observed during the COVID-19 pandemic. COVID-19 patients were characterized by elevated D-dimer levels on admission, reflecting enhanced COVID-19 related thrombogenicity. The prehospital evaluation by EMS may have played an important role for the timely revascularization for STEMI patients.

Systemic Inflammatory Response Syndrome Is a Major Determinant of Cardiovascular Outcome in Takotsubo Syndrome.

BACKGROUND: Recent insights have emphasized the importance of inflammatory response in takotsubo syndrome (TTS). We sought to evaluate the predictors of systemic inflammatory response syndrome (SIRS) and its impact on cardiovascular mortality after TTS.Methods and Results:The 215 TTS patients were retrospectively included between September 2008 and January 2018. SIRS was diagnosed in 96 patients (44.7%). They had lower left ventricular ejection fraction (LVEF) on admission (34.5% vs. 41.9%; P<0.001) and higher peak brain natriuretic peptide and troponin. At a median follow-up of 518 days, SIRS was associated with increased in-hospital mortality (14.6% vs. 5.0%; P=0.019), overall mortality (29.4% vs. 10.8%; P=0.002), and cardiovascular mortality (10.6% vs. 2.1%; P=0.026). A history of cancer (OR, 3.36; 95% CI: 1.54-7.31; P=0.002) and LVEF <40% at admission (OR, 2.31; 95% CI: 1.16-4.58; P=0.017) were identified as independent predictors of SIRS. On multivariate Cox regression analysis, SIRS (HR, 12.8; 95% CI: 1.58-104; P=0.017), age (HR, 1.09; 95% CI: 1.02-1.16; P=0.01), and LVEF <40% at discharge (HR, 9.88; 95% CI: 2.54-38.4; P=0.001) were independent predictors of cardiovascular death. CONCLUSIONS: SIRS was found in a large proportion of TTS patients and was associated with enhanced myocardial damage and adverse outcome in the acute phase. At long-term follow-up, SIRS remained an independent factor of cardiovascular death.

Periprocedural Predictors of New-Onset Conduction Abnormalities After Transcatheter Aortic Valve Replacement.

BACKGROUND: New-onset conduction abnormalities (CAs) following transcatheter aortic valve replacement (TAVR) are associated with hospital rehospitalization and long-term mortality, but available predictors are sparse. This study sought to determine clinical predictors of new-onset left bundle branch block (LBBB) and new permanent pacemaker (PPM) implantation in patients undergoing TAVR.Methods and Results:We enrolled 290 patients who received SAPIEN 3 (Edwards Lifesciences, Irvine, CA, USA; n=217) or Evolut R (Medtronic, Minneapolis, MN, USA; n=73) from a prospective registry at Nouvel Hôpital Civil, Strasbourg, France between September 2014 and February 2018. Of 242 patients without pre-existing LBBB, 114 (47%) experienced new-onset LBBB and/or new PPM implantation. A difference between membranous septal length and implantation depth (∆MSID) was the only predictor of CAs for both types of valves. In the multivariate analysis, PR interval and ∆MSID remained as sole predictors of CAs. The risk for adverse clinical events, including all-cause death, myocardial infarction, stroke, and heart failure hospitalization, was higher for patients with CAs as compared with patients without CAs (hazard ratio: 2.10; 95% confidence interval: 1.26 to 3.57; P=0.004). CONCLUSIONS: Computed tomography assessment of membranous septal anatomy and implantation depth predicted CAs after TAVR with new-generation valves. Future studies are required to identify whether adjustment of the implantation depth can reduce the risk of CAs and adverse clinical outcomes.

Thromboprophylaxis: balancing evidence and experience during the COVID-19 pandemic.

A common and potent consideration has recently entered the landscape of the novel coronavirus disease of 2019 (COVID-19): venous thromboembolism (VTE). COVID-19 has been associated to a distinctive related coagulopathy that shows unique characteristics. The research community has risen to the challenges posed by this « evolving COVID-19 coagulopathy ¼ and has made unprecedented efforts to promptly address its distinct characteristics. In such difficult time, both national and international societies of thrombosis and hemostasis released prompt and timely responses to guide recognition and management of COVID-19-related coagulopathy. However, latest guidelines released by the international Society on Thrombosis and Haemostasis (ISTH) on May 27, 2020, followed the American College of Chest Physicians (CHEST) on June 2, 2020 showed some discrepancies regarding thromboprophylaxis use. In this forum article, we would like to offer an updated focus on thromboprophylaxis with current incidence of VTE in ICU and non-ICU patients according to recent published studies; highlight the main differences regarding ISTH and CHEST guidelines; summarize and describe which are the key ongoing RCTs testing different anticoagulation strategies in patients with COVID-19; and finally set a proposal for COVID-19 coagulopathy specific risk factors and dedicated trials.

Left ventricular mechanics in the acute phase of Takotsubo cardiomyopathy: distinctive ballooning patterns translate into different diastolic properties.

Although apical and midventricular Takotsubo cardiomyopathies (TTCs) share common triggers and pathophysiological features, little is known about the potential differences in left ventricular (LV) mechanistic properties between these TTC phenotypes. We sought to investigate whether LV systolic and/or diastolic function, as assessed invasively by left heart catheterization (LHC), differ according to ballooning patterns in the acute phase of TTC. One hundred and fourteen TTC patients were retrospectively identified between January 2009 and December 2015 at the University Hospital of Strasbourg, France. A comprehensive list of LV quantitative parameters was derived from LHC analysis for each patient. We examined 2 groups of patients according to ballooning patterns in the acute phase of TTC: patients with apical ballooning ("Apical group"; n = 76) and those with midventricular ballooning ("Midventricular group"; n = 38). LV minimal diastolic pressure (8.72 ± 6.72 vs. 5.02 ± 6.08 mmHg; p = 0.004), LV end diastolic pressure (23.11 ± 8.32 vs. 18.84 ± 8.06 mmHg; p = 0.01), and LV diastolic stiffness (LV stiffness 1: 0.29 ± 0.23 vs. 18.84 ± 8.06 mmHg/mL; p = 0.04-LV stiffness 2: 0.16 ± 0.08 vs. 0.12 ± 0.05 mmHg/mL; p = 0.005) were significantly higher in patients with apical TTC than in the midventricular group. Concomitantly, these findings were associated with significantly higher BNP levels in the apical group (923.91 ± 1164.53 vs. 418.71 ± 557.75 pg/mL; p = 0.004) than in the midventricular group. In the acute phase of stress cardiomyopathy, the classic apical form of TTC is associated with poorer diastolic function compared to the midventricular ballooning variant, as assessed through direct invasive hemodynamic measurements using LHC.

RRAD mutation causes electrical and cytoskeletal defects in cardiomyocytes derived from a familial case of Brugada syndrome.

AIMS: The Brugada syndrome (BrS) is an inherited cardiac disorder predisposing to ventricular arrhythmias. Despite considerable efforts, its genetic basis and cellular mechanisms remain largely unknown. The objective of this study was to identify a new susceptibility gene for BrS through familial investigation. METHODS AND RESULTS: Whole-exome sequencing performed in a three-generation pedigree with five affected members allowed the identification of one rare non-synonymous substitution (p.R211H) in RRAD, the gene encoding the RAD GTPase, carried by all affected members of the family. Three additional rare missense variants were found in 3/186 unrelated index cases. We detected higher levels of RRAD transcripts in subepicardium than in subendocardium in human heart, and in the right ventricle outflow tract compared to the other cardiac compartments in mice. The p.R211H variant was then subjected to electrophysiological and structural investigations in human cardiomyocytes derived from induced pluripotent stem cells (iPSC-CMs). Cardiomyocytes derived from induced pluripotent stem cells from two affected family members exhibited reduced action potential upstroke velocity, prolonged action potentials and increased incidence of early afterdepolarizations, with decreased Na+ peak current amplitude and increased Na+ persistent current amplitude, as well as abnormal distribution of actin and less focal adhesions, compared with intra-familial control iPSC-CMs Insertion of p.R211H-RRAD variant in control iPSCs by genome editing confirmed these results. In addition, iPSC-CMs from affected patients exhibited a decreased L-type Ca2+ current amplitude. CONCLUSION: This study identified a potential new BrS-susceptibility gene, RRAD. Cardiomyocytes derived from induced pluripotent stem cells expressing RRAD variant recapitulated single-cell electrophysiological features of BrS, including altered Na+ current, as well as cytoskeleton disturbances.

Atrial arrhythmias in Takotsubo cardiomyopathy: incidence, predictive factors, and prognosis.

AIMS: Takotsubo cardiomyopathy (TTC) is a stress-related transient cardiomyopathy. It is unclear whether TTC is associated with poorer prognosis when atrial arrhythmia (AA), atrial fibrillation or flutter, occurs. The purpose of this study was to assess the incidence of AA in patients with TTC, predictive factors of AA, and its association with mortality. METHODS AND RESULTS: We studied 214 consecutive cases of TTC over 8 years. The study cohort was divided into two groups-those with newly diagnosed AA (AA-group) and those without (non-AA group). AA occurred in 24.8% of the patients. The AA group presented with lower left ventricular ejection fraction (LVEF) on admission and higher cardiac arrest rate. Admission and peak levels of troponin, B-type natriuretic peptide (BNP), C-reactive protein (CRP), and leucocytes were higher in the AA group. In-hospital, 30-day, cardiovascular, and all-cause mortality were significantly higher in the AA group. Independent predictors of newly diagnosed AA were troponin peak [odds ratio (OR) 1.03 (1.003-1.06); P = 0.029], CRP peak [OR 1.006 (1.001-1.01); P = 0.026], and LVEF on admission [OR 0.96 (0.93-0.99); P = 0.01]. Newly diagnosed AA was not predictive of mortality. The BNP peak [OR 1.00 (1.000-1.001); P = 0.022] and leucocytes peak [OR 1.095 (1.034-1.16); P = 0.002] were predictive factors of in-hospital mortality. LVEF upon discharge [OR 0.935 (0.899-0.972); P = 0.001] and leucocytes peak [OR 1.068 (1.000-1.139); P = 0.049] were predictive of cardiovascular death. CONCLUSION: Newly diagnosed AA is frequently observed in patients presenting with TTC and is associated with poorer short- and long-term prognosis. Inflammation, myocardial damage, and LVEF are predictors of AA onset and cardiovascular mortality.

Endothelial Microparticles From Acute Coronary Syndrome Patients Induce Premature Coronary Artery Endothelial Cell Aging and Thrombogenicity: Role of the Ang II/AT1 Receptor/NADPH Oxidase-Mediated Activation of MAPKs and PI3-Kinase Pathways.

BACKGROUND: Microparticles (MPs) have emerged as a surrogate marker of endothelial dysfunction and cardiovascular risk. This study examined the potential of MPs from senescent endothelial cells (ECs) or from patients with acute coronary syndrome (ACS) to promote premature EC aging and thrombogenicity. METHODS: Primary porcine coronary ECs were isolated from the left circumflex coronary artery. MPs were prepared from ECs and venous blood from patients with ACS (n=30) and from healthy volunteers (n=4) by sequential centrifugation. The level of endothelial senescence was assessed as senescence-associated ß-galactosidase activity using flow cytometry, oxidative stress using the redox-sensitive probe dihydroethidium, tissue factor activity using an enzymatic Tenase assay, the level of target protein expression by Western blot analysis, platelet aggregation using an aggregometer, and shear stress using a cone-and-plate viscometer. RESULTS: Senescence, as assessed by senescence-associated ß-galactosidase activity, was induced by the passaging of porcine coronary artery ECs from passage P1 to P4, and was associated with a progressive shedding of procoagulant MPs. Exposure of P1 ECs to MPs shed from senescent P3 cells or circulating MPs from ACS patients induced increased senescence-associated ß-galactosidase activity, oxidative stress, early phosphorylation of mitogen-activated protein kinases and Akt, and upregulation of p53, p21, and p16. Ex vivo, the prosenescent effect of circulating MPs from ACS patients was evidenced only under conditions of low shear stress. Depletion of endothelial-derived MPs from ACS patients reduced the induction of senescence. Prosenescent MPs promoted EC thrombogenicity through tissue factor upregulation, shedding of procoagulant MPs, endothelial nitric oxide synthase downregulation, and reduced nitric oxide-mediated inhibition of platelet aggregation. These MPs exhibited angiotensin-converting enzyme activity and upregulated AT1 receptors and angiotensin-converting enzyme in P1 ECs. Losartan, an AT1 receptor antagonist, and inhibitors of either mitogen-activated protein kinases or phosphoinositide 3-kinase prevented the MP-induced endothelial senescence. CONCLUSIONS: These findings indicate that endothelial-derived MPs from ACS patients induce premature endothelial senescence under atheroprone low shear stress and thrombogenicity through angiotensin II-induced redox-sensitive activation of mitogen-activated protein kinases and phosphoinositide 3-kinase/Akt. They further suggest that targeting endothelial-derived MP shedding and their bioactivity may be a promising therapeutic strategy to limit the development of an endothelial dysfunction post-ACS.

Early and Late Atrial Arrhythmias After Lung Transplantation　- Incidence, Predictive Factors and Impact on Mortality.

BACKGROUND: Atrial arrhythmias (AAs) are frequent after lung transplantation (LT) and late postoperatively. Several predictive factors of early postoperative AAs after LT have been identified but those of late AAs remain unknown. Whether AA after LT affects mortality is still being debated. This study assessed in a large cohort of LT patients the incidence of AAs early and late after surgery, their predictive factors and their effect on mortality.Methods and Results:We studied 271 consecutive LT patients over 9 years. Mean follow-up was 2.9±2.4 years. 33% patients developed postoperative AAs. Age (odds ratio (OR) 2.35; confidence interval (CI) [1.31-4.24]; P=0.004) and chronic obstructive pulmonary disease (OR 2.13; CI [1.12-4.03]; P=0.02) were independent predictive factors of early AAs. Late AAs occurred 2.2±2.7 years after transplant in 8.8% of the patients. Pretransplant systolic pulmonary arterial pressure (PTsPAP) was the only independent predictive factor of late AA (OR 1.028; CI [1.001-1.056]; P=0.04). Double LT was associated with long-term freedom from atrial fibrillation (AF) but not from atrial flutter (AFL). Early and late AAs after surgery had no effect on mortality. Double LT was associated with better survival. CONCLUSIONS: Early AA following LT is common in contrast with the low occurrence of late, often organized, AA. Early and late AAs do not affect mortality. PTsPAP is an independent predictor of late AA. Double LT protects against late AF but not AFL.

Unexpected Problems of Antithrombotic Therapy with An Unusual Side Effect of Vitamin K Antagonists after Mitral Valve Replacement.

Except for bleeding complications, vitamin K antagonists (VKAs) are known to have few undesirable side effects. Herein is presented the case of a 45-year-old woman in whom liver damage was induced by fluindione and warfarin after mitral valve replacement. Hepatotoxicity is a rare complication of VKAs, both in the French National and Drug Safety registry and the medical literature. A diagnosis of VKA-induced drug damage was confirmed by the absence of other etiologies, the chronological sequence, recurrence after re-exposure to VKA, and rapid improvements after discontinuation of the drug. Despite possible cross-reactions between VKAs, the re-introduction of acenocoumarol was successfully achieved, with no recurrence of biological disturbances.

Impact of Malignancies in the Early and Late Time Course of Takotsubo Cardiomyopathy.

BACKGROUND: Although the relationship between malignancies and catecholamine-induced myocardial stunning remains largely speculative, it has been suggested that the presence of cancer may lower the threshold for stress stimuli and/or may aggravate cardiac adrenoreceptor sensitivity. We sought to investigate whether associations exist between a previous or current diagnosis of malignancy, diagnostic parameters during hospitalization and death in takotsubo. METHODS AND RESULTS: The 154 takotsubo patients were retrospectively identified between May 2008 and December 2014. Previous history of malignancy was identified in 44 patients (28.5%). Cardiac arrest was present at admission in 13 patients (8.4%). Intra-aortic balloon pump was inserted in 16 patients (10.4%). In patients with malignancy, higher B-type natriuretic peptide (BNP), leukocyte and C-reactive protein (CRP) peaks could be observed during the hospital phase. Initial impairment of left ventricular ejection fraction was negatively related to BNP, leukocyte, and CRP peaks. At a median follow-up of 364 days, all-cause death occurred in 41 patients (26.6%) and cardiac death in 12 patients (7.7%). Multivariate Cox regression analysis identified malignancy (hazard ratio 4.77 (1.02-22.17), leukocyte peak and age as independent predictors of cardiac death. Malignancy (2.62 (1.26-5.44), leukocyte peak (1.05 (1.01-1.08) and initial cardiac arrest (6.68 (2.47-18.01) were identified as independent predictors of overall mortality. CONCLUSIONS: In the present takotsubo patients, the prevalence of malignancy was high and may have affected cardiovascular outcomes through the activation of inflammatory and neurohormonal mechanisms. (Circ J 2016; 80: 2192-2198).

Driver domains in persistent atrial fibrillation.

BACKGROUND: Specific noninvasive signal processing was applied to identify drivers in distinct categories of persistent atrial fibrillation (AF). METHODS AND RESULTS: In 103 consecutive patients with persistent AF, accurate biatrial geometry relative to an array of 252 body surface electrodes was obtained from a noncontrast computed tomography scan. The reconstructed unipolar AF electrograms acquired at bedside from multiple windows (duration, 9±1 s) were signal processed to identify the drivers (focal or reentrant activity) and their cumulative density map. The driver domains were catheter ablated by using AF termination as the procedural end point in comparison with the stepwise-ablation control group. The maps showed incessantly changing beat-to-beat wave fronts and varying spatiotemporal behavior of driver activities. Reentries were not sustained (median, 2.6 rotations lasting 449±89 ms), meandered substantially but recurred repetitively in the same region. In total, 4720 drivers were identified in 103 patients: 3802 (80.5%) reentries and 918 (19.5%) focal breakthroughs; most of them colocalized. Of these, 69% reentries and 71% foci were in the left atrium. Driver ablation alone terminated 75% and 15% of persistent and long-lasting AF, respectively. The number of targeted driver regions increased with the duration of continuous AF: 2 in patients presenting in sinus rhythm, 3 in AF lasting 1 to 3 months, 4 in AF lasting 4 to 6 months, and 6 in AF lasting longer. The termination rate sharply declined after 6 months. The mean radiofrequency delivery to AF termination was 28±17 minutes versus 65±33 minutes in the control group (P<0.0001). At 12 months, 85% patients with AF termination were free from AF, similar to the control population (87%,); P=not significant. CONCLUSIONS: Persistent AF in early months is maintained predominantly by drivers clustered in a few regions, most of them being unstable reentries.

Impact of Substrate-Based Ablation of Ventricular Tachycardia on Cardiac Mortality in Patients With Implantable Cardioverter-Defibrillators.

INTRODUCTION: This study sought to determine if the acute procedural outcome of ventricular tachycardia (VT) substrate ablation is associated with a mortality benefit in patients with implantable cardioverter-defibrillators (ICD). METHODS AND RESULTS: A total of 195 ICD recipients (65 ± 11years) with ischemic or nonischemic dilated cardiomyopathy underwent substrate-based ablation targeting elimination of local abnormal ventricular activities (LAVA). Acute procedural success, which was defined as elimination of all identified LAVA in addition to the lack of VT inducibility, was achieved in 95 (49%) patients. During a median follow-up of 23 months, patients with acute procedure success had a significantly lower incidence of ICD shocks compared to those with ablation failure (8% vs. 30%, P < 0.001). In multivariate analysis, acute procedural success was associated with a lower risk of VT recurrence (hazard ratio [HR] 0.30, 95% confidence interval [CI] 0.18-0.49, P < 0.001) and all-cause mortality (HR 0.32, 95% CI 0.17-0.60, P < 0.001). While the impact of ablation success on mortality was not statistically significant in patients with LVEF > 35% (HR 0.45, 95% CI 0.15-1.34, P = 0.15) and those with NYHA class I/II (HR 0.63, 95% CI 0.29-1.40, P = 0.26), it was marked in patients with LVEF ≤ 35% (HR 0.30, 95% CI 0.14-0.62, P = 0.001) and NYHA class III/IV (HR 0.17, 95% CI 0.05-0.57, P = 0.004). CONCLUSIONS: LAVA elimination in addition to VT noninducibility as a procedural outcome for substrate-based ablation is associated with reduced mortality and better VT-free survival during follow-up. This prognostic benefit may be most pronounced in patients with severe heart failure as indicated by severely depressed LV function and NYHA class III/IV symptoms.

Do atrial differences in endothelial damage, leukocyte and platelet activation, or tissue factor activity contribute to chamber-specific thrombogenic status in patients with atrial fibrillation?

BACKGROUND: Thrombi form mainly in the left rather than the right atria of patients with atrial fibrillation (AF), the reason of this predilection being unknown. OBJECTIVE: The purpose of this study was to investigate whether atrial-specific differences in endothelial damage, leukocyte activation, platelet stimulation, and tissue factor activity occur in patients with AF. METHODS: Twenty-two patients (16 men, 6 women; age 56 ± 8 years; 16 paroxysmal AF, 6 persistent AF) with AF undergoing pulmonary vein isolation were investigated. Blood samples from the left and the right atrium were obtained at the start of the procedure. Microparticles (MPs) released by apoptotic/stimulated cells were measured by capture assays. Their procoagulant abilities were quantified by functional prothrombinase and tissue factor assays and their cellular origin were determined (endothelium, platelet, leukocyte). Platelet reactivity was evaluated by whole blood flow cytometry for expression of platelet P-selectin (CD62P), active glycoprotein IIb/IIIa receptor (PAC-1). Platelet aggregation was evaluated using ADP, TRAP and collagen-induced whole blood aggregometry. RESULTS: There were no atrial-specific differences in the levels of total procoagulant MPs, leukocyte-derived-MPs or platelet-derived MPs. Conversely, endothelial-derived MPs and tissue factor activity and collagen-induced platelet aggregation were slightly elevated in the right atrium (P < 0.05). CONCLUSIONS: Our data show no evidence for increased thrombogenic status in the left atrium that would account for its greater propensity for thrombus formation in patients with AF.

Pulmonary vein isolation using a circular, open irrigated mapping and ablation catheter (nMARQ): a report on feasibility and efficacy.

AIMS: Pulmonary vein isolation (PVI) is the mainstay of interventional treatment of paroxysmal atrial fibrillation (PAF). We report on the feasibility and efficacy of a novel, open-irrigated mapping and radiofrequency (RF) ablation catheter. METHODS AND RESULTS: Thirty-nine consecutive patients (pts; age 60 ± 10 years, 8 females) suffering from drug-refractory PAF referred for PVI were included in this prospective study. Pulmonary vein isolation was performed with the use of a novel 10-pole circular, open-irrigated mapping and ablation catheter (nMARQ, Biosense Webster). Outcome parameters were the acute success rate in establishing complete PVI and the rate of sustained sinus rhythm (SR) during follow-up (FU). Ten patients underwent a repeat procedure for recurrent AF. Ninety-eight percent of the PVs could be acutely isolated using solely the nMARQ catheter by applying a mean total of 10.0 ± 4.6 min of RF energy. The mean total procedure duration was 86 ± 29 min, and the mean fluoroscopy time was 22.2 ± 6.5 min, respectively. Transient reconnection provoked by adenosine was observed in 10 of 24 patients, most frequently in the right superior PV. Cardiac tamponade related to transseptal puncture occurred in one patient. Reconnected PVs could be identified as a source of recurrent AF in 9 of 10 patients undergoing a repeat procedure. Single and multiple procedure success rates during a mean FU of 140 ± 75 days were 66 and 77%, respectively. CONCLUSION: Irrigated multi-electrode RF ablation is fast and effective, providing a high rate of isolated PVs without the need of touch-up lesions. Success rates were comparable with other techniques with a low complication rate. Recurrences of AF were mainly due to recovered pulmonary vein/left atrium conduction.