Is Conduction System Pacing a Valuable Alternative to Biventricular Pacing for Cardiac Resynchronization Therapy?

Cardiac resynchronization therapy (CRT) significantly improves clinical outcomes in patients with ventricular systolic dysfunction and dyssynchrony. Biventricular pacing (BVP) has a class IA recommendation for patients with symptomatic heart failure with reduced ejection fraction (HFrEF) and left bundle branch block (LBBB). However, approximately 30% of patients have a poor therapeutic response and do not achieve real clinical benefit. Pre-implant imaging, together with tailored programming and dedicated device algorithms, have been proposed as possible tools to improve success rate but have shown inconsistent results. Over the last few years, conduction system pacing (CSP) is becoming a real and attractive alternative to standard BVP as it can restore narrow QRS in patients with bundle branch block (BBB) by stimulating and recruiting the cardiac conduction system, thus ensuring true resynchronization. It includes His bundle pacing (HBP) and left bundle branch area pacing (LBBAP). Preliminary data coming from small single-center experiences are very promising and have laid the basis for currently ongoing randomized controlled trials comparing CSP with BVP. The purpose of this review is to delve into the emerging role of CSP as an alternative method of achieving CRT. After framing CSP in a historical perspective, the pathophysiological rationale and available clinical evidence will be examined, and crucial technical aspects will be discussed. Finally, evidence gaps and future perspectives on CSP as a technique of choice to deliver CRT will be summarized.

Cardiac imaging for the prediction of sudden cardiac arrest in patients with heart failure.

The identification of heart failure (HF) patients at risk for arrhythmic sudden cardiac arrest (SCA) is a major challenge in the cardiovascular field. In addition to optimal medical treatment for HF, implantable cardioverter defibrillator (ICD) is currently recommended to prevent SCA in patients with reduced left ventricular ejection fraction (LVEF). The indication for an ICD implantation, in addition to HF etiology, New York Health Association (NYHA) class and life expectancy, mainly depends on LVEF value at echocardiography. However, the actual role of LVEF in the prediction of SCA has recently been debated, while newer multimodality imaging techniques with increased prognostic accuracy have been developed. Speckle tracking imaging allows the quantification of mechanical dispersion, a marker of electrophysiological heterogeneity predisposing to malignant arrhythmias, while advanced cardiac magnetic resonance techniques such as myocardial T1-mapping and extracellular volume fraction assessment allow the evaluation of interstitial diffuse fibrosis. Nuclear imaging is helpful for the appraisal of sympathetic nervous system dysfunction, while newer computed tomography techniques assessing myocardial delayed enhancement allow the identification of focal myocardial scar. This review will focus on the most modern advances in the field of cardiovascular imaging along with its applications for the prediction of SCA in patients with HF. Modern artificial intelligence applications in cardiovascular imaging will also be discussed.

Impact of Right Ventricular Pacing in Patients With TAVR Undergoing Permanent Pacemaker Implantation.

BACKGROUND: Long-term right ventricular pacing (VP) has been related to negative left ventricular remodeling and heart failure (HF), but there is a lack of evidence regarding the prognostic impact on transcatheter aortic valve replacement (TAVR) patients. OBJECTIVES: The aim of the PACE-TAVI registry is to evaluate the association of high percentage of VP with adverse outcomes in patients with pacemaker implantation after TAVR. METHODS: PACE-TAVI is an international multicenter registry of all consecutive TAVR patients who underwent permanent pacemaker implantation for conduction disturbances in the first 30 days after the procedure. Patients were divided into 2 subgroups according to the percentage of VP (<40% vs ≥40%) at pacemaker interrogation. The primary endpoint was the composite of cardiovascular mortality or hospitalization for HF. RESULTS: A total of 377 patients were enrolled, 158 with VP <40% and 219 with VP ≥40%. After multivariable adjustment, VP ≥40% was associated with a higher incidence of the primary endpoint (HR: 2.76; 95% CI: 1.39-5.51; P = 0.004), first HF hospitalization (HR: 3.37; 95% CI: 1.50-7.54; P = 0.003), and cardiovascular death (HR: 3.77; 95% CI: 1.02-13.88; P = 0.04), while the incidence of all-cause death was not significantly different (HR: 2.17; 95% CI: 0.80-5.90; P = 0.13). Patients with VP ≥ 40% showed a higher New York Heart Association functional class both at 1 year (P = 0.009) and at last available follow-up (P = 0.04) and a nonsignificant reduction of left ventricular ejection fraction (P = 0.18) on 1-year echocardiography, while patients with VP <40% showed significant improvement (P = 0.009). CONCLUSIONS: In TAVR patients undergoing permanent pacemaker implantation, a high percentage of right VP at follow-up is associated with an increased risk for cardiovascular death and HF hospitalization. These findings suggest the opportunity to minimize right VP through dedicated algorithms in post-TAVR patients without complete atrioventricular block and to evaluate a more physiological VP modality in patients with persistent complete atrioventricular block.

Embolic Stroke of Undetermined Source: Role of Implantable Loop Recorder in Secondary Prevention.

BACKGROUND AND AIMS: Atrial fibrillation (AF) is the most important cause of embolic stroke of undetermined source (ESUS). Implantable loop recorder (ILR) demonstrated the highest sensitivity for detecting it. This register was created to confirm the high prevalence of AF in patients after ESUS and to verify possible benefits on clinical outcomes such as TIA (Transient Ischaemic Attack)/stroke recurrence and death using ILR. METHODS: A total of 278 patients admitted to "Molinette" Hospital in Stroke Unit department between 2011 and 2016, diagnosed with ESUS, underwent ILR implantation if they had at least one risk factor for AF. A total of 165 patients admitted to other departments in the same center for the same pathology, without ILR, represent the control group. We used propensity score to select 132 patients from each group (matching age, sex, CHADS-VASC, and HAS-BLEED baseline characteristics). RESULTS: The detection rate of AF episodes was significantly higher in the ILR group (p < 0.001). No significant protective role of ILR for clinical endpoints was found on univariate analysis, although a trend towards significance has been pointed for the composite outcome of death and ischemic events recurrence (OR 0.52, CI 0.26-1.04, p = 0.06). A protective role of ILR was found for deaths (OR 0.4, CI 0.17-0.94, p 0.03) and for the composite outcome (OR 0.41, CI 0.19-0.87, p 0.02) on multivariate analysis in the best subsets. CONCLUSION: With our statistical models, we identified a significant clinical benefit from ILR monitoring, evidenced by a trend of less death and TIA/stroke recurrence and relevant ILR protection for prediction of TIA/stroke recurrence.

Implantation of cardiac electronic devices in active COVID-19 patients: Results from an international survey.

BACKGROUND: Cardiac implantable electronic device (CIED) implantation rates as well as the clinical and procedural characteristics and outcomes in patients with known active coronavirus disease 2019 (COVID-19) are unknown. OBJECTIVE: The purpose of this study was to gather information regarding CIED procedures during active COVID-19, performed with personal protective equipment, based on an international survey. METHODS: Fifty-three centers from 13 countries across 4 continents provided information on 166 patients with known active COVID-19 who underwent a CIED procedure. RESULTS: The CIED procedure rate in 133,655 hospitalized COVID-19 patients ranged from 0 to 16.2 per 1000 patients (P <.001). Most devices were implanted due to high-degree/complete atrioventricular block (112 [67.5%]) or sick sinus syndrome (31 [18.7%]). Of the 166 patients in the study survey, the 30-day complication rate was 13.9% and the 180-day mortality rate was 9.6%. One patient had a fatal outcome as a direct result of the procedure. Differences in patient and procedural characteristics and outcomes were found between Europe and North America. An older population (76.6 vs 66 years; P <.001) with a nonsignificant higher complication rate (16.5% vs 7.7%; P = .2) was observed in Europe vs North America, whereas higher rates of critically ill patients (33.3% vs 3.3%; P <.001) and mortality (26.9% vs 5%; P = .002) were observed in North America vs Europe. CONCLUSION: CIED procedure rates during known active COVID-19 disease varied greatly, from 0 to 16.2 per 1000 hospitalized COVID-19 patients worldwide. Patients with active COVID-19 infection who underwent CIED implantation had high complication and mortality rates. Operators should take these risks into consideration before proceeding with CIED implantation in active COVID-19 patients.

Prognostic role of left atrial enlargement in patients with implantable cardioverter defibrillators for primary prevention.

PURPOSE: Left atrial volume index (LAVI) is a predictor of heart failure and adverse events, irrespective of left ventricular systolic function. The role of LAVI in the prediction of appropriate implantable cardioverter-defibrillator (ICD) therapies is currently unclear and was the focus of this study. METHODS: Consecutive heart failure patients with ischaemic (ICM) or idiopathic (DCM) aetiology receiving ICD for primary prevention were included. The primary endpoint was the occurrence of appropriate ICD therapies (ATs): shocks or antitachycardia pacing (ATP). Inappropriate ICD shocks were also assessed as secondary endpoint. RESULTS: Among 198 included patients, severe left atrial dilatation (SLAE = LAVI ≥ 60 ml/m2) was present in 54 (27%). SLAE patients had a higher prevalence of NYHA class ≥ III, severe mitral regurgitation and atrial fibrillation history. During a median follow-up of 45 months (IQR 25-68), ATs occurred more frequently in SLAE group (33% vs. 15%, p = .007) as well as appropriate shocks (24% vs. 10%, p = .014). At multivariate analysis SLAE was an independent predictor of ATs (OR 3.19, 95% CI 1.38-7.38, p = .007). Inappropriate shocks were associated with AF during implantation (p = .03), but not with SLAE (p = .009). CONCLUSION: In DCM or ICM patients candidate to receive an ICD for primary prevention, a severely enlarged left atrium is a predictive factor for ATs (shocks or ATP). The risk of inappropriate shocks was increased in patients with atrial fibrillation, rather than SLAE.

Efficacy of new medical therapies in patients with heart failure, reduced ejection fraction, and chronic kidney disease already receiving neurohormonal inhibitors: a network meta-analysis.

AIMS: We assessed the efficacy of the drugs developed after neurohormonal inhibition (NEUi) in patients with heart failure (HF) with reduced ejection fraction (HFrEF) and concomitant chronic kidney disease (CKD). METHODS AND RESULTS: The literature was systematically searched for phase 3 randomized controlled trials (RCTs) involving ≥90% patients with left ventricular ejection fraction <45%, of whom <30% were acutely decompensated, and with published information about the subgroup of estimated glomerular filtration rate <60 mL/min/1.73 m2. Six RCTs were included in a study-level network meta-analysis evaluating the effect of NEUi, ivabradine, angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter-2 inhibitors (SGLT2i), vericiguat, and omecamtiv mecarbil (OM) on a composite outcome of cardiovascular death or hospitalization for HF. In a fixed-effects model, SGLT2i [hazard ratio (HR) 0.78, 95% credible interval (CrI) 0.69-0.89], ARNI (HR 0.79, 95% CrI 0.69-0.90), and ivabradine (HR 0.82, 95% CrI 0.69-0.98) decreased the risk of the composite outcome vs. NEUi, whereas OM did not (HR 0.98, 95% CrI 0.89-1.10). A trend for improved outcome was also found for vericiguat (HR 0.90, 95% CrI 0.80-1.00). In indirect comparisons, both SLGT2i (HR 0.80, 95% CrI 0.68-0.94) and ARNI (HR 0.80, 95% CrI 0.68-0.95) reduced the risk vs. OM; furthermore, there was a trend for a greater benefit of SGLT2i vs. vericiguat (HR 0.88, 95% CrI 0.73-1.00) and ivabradine vs. OM (HR 0.84, 95% CrI 0.68-1.00). Results were comparable in a random-effects model and in sensitivity analyses. Surface under the cumulative ranking area scores were 81.8%, 80.8%, 68.9%, 44.2%, 16.6%, and 7.8% for SGLT2i, ARNI, ivabradine, vericiguat, OM, and NEUi, respectively. CONCLUSION: Expanding pharmacotherapy beyond NEUi improves outcomes in HFrEF with CKD.

Effect of sacubitril/valsartan on investigator-reported ventricular arrhythmias in PARADIGM-HF.

AIMS: Sudden death is a leading cause of mortality in heart failure with reduced ejection fraction (HFrEF). In PARADIGM-HF, sacubitril/valsartan reduced the incidence of sudden death. The purpose of this post hoc study was to analyse the effect of sacubitril/valsartan, compared to enalapril, on the incidence of ventricular arrhythmias. METHODS AND RESULTS: Adverse event reports related to ventricular arrhythmias were examined in PARADIGM-HF. The effect of randomized treatment on two arrhythmia outcomes was analysed: ventricular arrhythmias and the composite of a ventricular arrhythmia, implantable cardioverter defibrillator (ICD) shock or resuscitated cardiac arrest. The risk of death related to a ventricular arrhythmia was examined in time-updated models. The interaction between heart failure aetiology, or baseline ICD/cardiac resynchronization therapy-defibrillator (CRT-D) use, and the effect of sacubitril/valsartan was analysed. Of the 8399 participants, 333 (4.0%) reported a ventricular arrhythmia and 372 (4.4%) the composite arrhythmia outcome. Ventricular arrhythmias were associated with higher mortality. Compared with enalapril, sacubitril/valsartan reduced the risk of a ventricular arrhythmia (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.62-0.95; p = 0.015) and the composite arrhythmia outcome (HR 0.79, 95% CI 0.65-0.97; p = 0.025). The treatment effect was maintained after adjustment and accounting for the competing risk of death. Baseline ICD/CRT-D use did not modify the effect of sacubitril/valsartan, but aetiology did: HR in patients with an ischaemic aetiology 0.93 (95% CI 0.71-1.21) versus 0.53 (95% CI 0.37-0.78) in those without an ischaemic aetiology (p for interaction = 0.020). CONCLUSIONS: Sacubitril/valsartan reduced the incidence of investigator-reported ventricular arrhythmias in patients with HFrEF. This effect may have been greater in patients with a non-ischaemic aetiology.

Successful Percutaneous Retrieval of an Embolized Left Atrial Appendage Occluder.

A 75-year-old man with a previous mitral valve repair experienced embolization of a left atrial appendage occlusion device in the left atrium. The device was successfully retrieved using a double snaring technique, without the need for open surgery. This is an unusual report of left atrial appendage occluder retrieval, confirming the feasibility of the technique and the high flexibility of the device. (Level of Difficulty: Advanced.).

In-hospital myocardial infarction and adherence to evidence-based drug therapies: a real-world evaluation.

OBJECTIVES: This study aimed to measure adherence to chronic polytherapy following an acute myocardial infarction (AMI) and to find out associations between adherence and the setting of AMI onset (in vs out of hospital) as well as other determinants. DESIGN: Retrospective follow-up study. SETTING: Population living in the Lazio Region, Italy. PARTICIPANTS: This study included 25 779 hospitalised patients with a first diagnosis of AMI in 2012-2016, after the exclusion of those with hospital admission for AMI or related causes in the previous 5 years. PRIMARY AND SECONDARY OUTCOME MEASURES: Patients were classified as in-hospital AMI (IH-AMI) or out of hospital AMI (OH-AMI) according to present-on-admission codes. Adherence was measured based on prescription claims during a 6-month follow-up after hospital discharge, using medication possession ratio (MPR). Adherence to chronic polytherapy was defined as MPR ≥75% to at least 3 of the following medications: antithrombotics, betablockers, ACE inhibitors/angiotensin receptor blockers and statins. RESULTS: Among the entire cohort, 1 044 (4%) patients suffered IH-AMI. Overall, 15 440 (60%) patients were deemed adherent to chronic polytherapy. Female gender, older age, mental disorders, renal disease, asthma and ongoing concomitant treatments were factors associated with poor adherence. By contrast, patients with more severe AMI and those already taking evidence-based (E-B) drugs were more likely to be adherent. A strong association between the setting of AMI onset and adherence was observed: IH-AMI patients were 46% less likely to be adherent to E-B medications during their 6-month follow-up as compared with OH-AMI patients (OR 0.54; 95% CI 0.47 to 0.62; p<0.001). CONCLUSION: Pharmacotherapy is not consistent with clinical guidelines, especially for IH-AMI patients. Our findings provide evidence on a previously unidentified groups of patients at risk for poor adherence, who might benefit from greater medical attention and dedicated healthcare interventions.

Transcatheter ablation for atrial fibrillation in patients with hypertrophic cardiomyopathy: Long-term results and clinical outcomes.

INTRODUCTION: Radiofrequency transcatheter ablation (RFCA) for atrial fibrillation (AF) in patients with hypertrophic cardiomyopathy (HCM) has been proven feasible. However, the long-term results of RFCA and its impact on clinical course of HCM are unknown. The aim of this study was to analyse clinical outcomes and long-term efficacy of RFCA in a multicentre cohort of patients with HCM and concomitant AF. METHODS: Patients with HCM and AF consecutively undergoing RFCA were included. Ablation failure was defined as recurrence of AF, atrial tachycardia, or flutter lasting more than 3 min and occurring after the blanking period. RESULTS: Overall, 116 patients with symptomatic AF refractory to antiarrhythmic drugs were included. Over a median follow-up of 6.0 years (interquartile range: 3.0-8.9 years) recurrence rate after a single RFCA was 32.3 per 100 patient/years with 26% of patients free from AF relapses at 6-year follow-up. Among patients experiencing AF recurrence, 51 (66%) underwent at least one redo-procedure. The overall recurrence rate considering redo-procedures was 12.6 per 100 patients/years with 53% of patients free from AF relapses at 6 years. At last follow-up, with an average of 1.6 procedures, 67 (61%) patients were in sinus rhythm (SR). Patients remaining in SR showed better functional status compared with those experiencing arrhythmic recurrences (NYHA Class 1.6 ± 0.1 vs. 2.0 ± 0.1, p = .009). CONCLUSIONS: RFCA of AF in HCM patients is an effective and safe strategy favoring long-term SR maintenance, reduction of atrial arrhythmic events, and improved functional status. However, most patients need repeat procedures and continuation of antiarrhythmic drugs.

Electrocardiographic and clinical predictors for permanent pacemaker requirement after transcatheter aortic valve implantation: a 10-year single center experience.

BACKGROUND: The aim of this study is to identify clinical, electrocardiographic (ECG) and procedural predictors for permanent pacemaker (PPM) requirement after transaortic valve implantation (TAVI). METHODS: All consecutive patients with severe symptomatic aortic stenosis (SSAS) undergoing TAVI at our single center were included in the study and prospectively followed. All patients had standard 12-leads ECGs recordings before and after TAVI and continuous ECG monitoring during hospital stay. Primary endpoint was to identify electrocardiographic predictors of PPM implantation after TAVI; secondary endpoint was to ascertain other clinical or procedure-related predictive factors of PPM need. PPM implantation was further arbitrarily divided into early and late one (beyond the 3rd day). RESULTS: Among the 431 patients undergoing TAVI between 2008 and 2018, 77 (18%) needed PPM implantation; 47 (11%) had an early procedure, and 30 (7%) a late implant. Preoperative right bundle branch block (RBBB) implies more than five-fold increase of the risk of PPM implantation (OR 5.19, CI 1.99-13.56, P=0.001), whereas the use of a self-expandable prosthesis is associated with an almost three-fold increase of the risk (OR 2.60, CI 1.28-5.28, P=0.008). In the late PPM implantation subgroup, only the history of syncope retains a significant association with such an increased risk (OR 2.71, CI 1.09-6.75, P=0.032). CONCLUSIONS: The need of a PPM in the individual TAVI patient is hardly predictable. However, the finding of pre-existing RBBB, the use of self-expandable prosthesis and history of syncope can individuate patients at increased risk.

Prevalence and incidence of intra-ventricular conduction delays and outcomes in patients with heart failure and reduced ejection fraction: insights from PARADIGM-HF and ATMOSPHERE.

AIMS: The importance of intra-ventricular conduction delay (IVCD), the incidence of new IVCD and its relationship to outcomes in heart failure and reduced ejection fraction (HFrEF) are not well studied. We addressed these questions in the PARADIGM-HF and ATMOSPHERE trials. METHODS AND RESULTS: The risk of the primary composite outcome of cardiovascular death or heart failure hospitalization and all-cause mortality were estimated by use of Cox regression according to baseline QRS duration and morphology in 11 861 patients without an intracardiac device. At baseline, 1789 (15.1%) patients had left bundle branch block (LBBB), 524 (4.4%) right bundle branch block (RBBB), 454 (3.8%) non-specific IVCD, 2588 (21.8%) 'mildly abnormal' QRS (110-129 ms) and 6506 (54.9%) QRS <110 ms. During a median follow-up of 2.5 years, the risk of the primary composite endpoint was higher among those with a wide QRS, irrespective of morphology: hazard ratios (95% confidence interval) LBBB 1.36 (1.23-1.50), RBBB 1.54 (1.31-1.79), non-specific IVCD 1.65 (1.40-1.94) and QRS 110-129 ms 1.35 (1.23-1.47), compared with QRS duration <110 ms. A total of 1234 (15.6%) patients developed new-onset QRS widening ≥130 ms (6.1 per 100 patient-years). Incident LBBB occurred in 495 (6.3%) patients (2.4 per 100 patient-years) and was associated with a higher risk of the primary composite outcome [hazard ratio 1.42 (1.12-1.82)]. CONCLUSION: In patients with HFrEF, a wide QRS was associated with worse clinical outcomes irrespective of morphology. The annual incidence of new-onset LBBB was around 2.5%, and associated with a higher risk of adverse outcomes, highlighting the importance of repeat electrocardiogram review. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT0083658 (ATMOSPHERE) and NCT01035255 (PARADIGM-HF).

Long-term percentage of ventricular pacing in patients requiring pacemaker implantation after transcatheter aortic valve replacement: A multicenter 10-year experience.

BACKGROUND: Recent studies suggest that atrioventricular (AV) conduction may recover after pacemaker (PM) implantation following transcatheter aortic valve replacement (TAVR), but little is known about long-term follow-up of such patients. OBJECTIVE: The purpose of this study was to evaluate the long-term percentage of right ventricular pacing in patients who underwent TAVR and required PM implantation stratified based on the indication for permanent pacing. METHODS: Retrospective analysis of all consecutive patients who underwent TAVR from February 2008 to August 2019 at 3 centers was performed. Patients already implanted with a PM/implantable cardioverter-defibrillator (ICD) before TAVR, implanted with a cardiac resynchronization therapy device, or implanted >30 days after TAVR were excluded. Eligible patients were divided into 2 groups based on the presence (persistent atrioventricular block [AVB] group) or absence (nonpersistent AVB group) of persistent third-degree AVB after TAVR. RESULTS: A total of 1594 patients underwent TAVR. Two hundred four patients were implanted with a PM or ICD after TAVR and 32 met exclusion criteria, so 172 patients were eligible (median time TAVR-PM implant 4 days) for a total of 352 follow-up visits analyzed. A significant difference in the percentage of ventricular pacing was observed at follow-up performed 7-90 days after implantation (98% persistent AVB group vs 8% nonpersistent AVB group; P <.001). This difference remained significant at follow-up performed 91-270 days (95% vs 3.5%; P <.001), 271-540 days (95.5% vs 3%; P = .006), and 541-900 days (97.4% vs 2.2%; P <.001) after implantation. CONCLUSION: Patients requiring PM implantation due to persistent third-degree AVB after TAVR were less likely to show AV conduction recovery, whereas patients implanted for other indications showed a low percentage of pacing during follow-up.

S-ICD lead dislodgement in a young isometric athlete: A rare complication.

The subcutaneous implantable cardioverter defibrillator (S-ICD) is an alternative to transvenous ICD in patients who do not need cardiac pacing. We report the case of a young isometric athlete who received S-ICD for primary prevention of sudden death. Lead dislodgement and myopotential noise oversensing during isometric training led to inappropriate shock, and a surgical revision was performed. During the procedure, strong fibrous adhesions were found, requiring polytetrafluoroethylene dilator sheaths. The S-ICD was finally reimplanted. Despite continued isometric training, no more myopotential oversensing occurred after 1-year follow-up. The present case highlights the possible higher risks of lead complication in an isometric athlete and the uncommon effort in removing an old-generation subcutaneous defibrillator lead.

Cardiovascular Considerations in Treating Patients With Coronavirus Disease 2019 (COVID-19).

A novel betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly across the globe since December 2019. Coronavirus disease 2019 (COVID-19) has a significantly higher mortality rate than seasonal influenza and has disproportionately affected older adults, especially those with cardiovascular disease and related risk factors. Adverse cardiovascular sequelae, such as myocarditis, acute myocardial infarction, and heart failure, have been reported in patients with COVID-19. No established treatment is currently available; however, several therapies, including remdesivir, hydroxychloroquine and chloroquine, and interleukin (IL)-6 inhibitors, are being used off-label and evaluated in ongoing clinical trials. Considering these therapies are not familiar to cardiovascular clinicians managing these patients, this review describes the pharmacology of these therapies in the context of their use in patients with cardiovascular-related conditions.

Zero-fluoroscopy atrial fibrillation ablation in the presence of a patent foramen ovale: a multicentre experience.

INTRODUCTION: Atrial fibrillation ablation has historically been guided by fluoroscopy, with the related enhanced risk deriving from radiation. Fluoroscopy exposure may be confined to guide the transseptal puncture. Small sample size study presented a new methodology to perform a totally fluoroless atrial fibrillation ablation in the case of a patent foramen ovale (PFO). We evaluated this methodology in a large sample size of patients and a multicentre experience. METHODS AND RESULTS: Two hundred and fifty paroxysmal atrial fibrillation patients referred for first atrial fibrillation ablation with a CARTO3 electroanatomic mapping system were enrolled. In 58 out of 250 patients, a PFO allowed crossing of the interatrial septum, and a completely fluoroless ablation was performed applying the new method (Group A). In the remaining patients, a standard transseptal puncture was performed (Group B). Pulmonary vein isolation was achieved in all patients with comparable procedural and clinical outcomes at short- and long-term follow-up. CONCLUSION: The presence of a PFO may allow a completely fluoroless well tolerated and effective atrial fibrillation ablation. Probing the fossa ovalis looking for the PFO during the procedure is desirable, as it is not time-consuming and can potentially be done in every patient undergoing atrial fibrillation ablation.

Relationship between heart rate and outcomes in patients in sinus rhythm or atrial fibrillation with heart failure and reduced ejection fraction.

AIMS: To investigate the relationship between heart rate and outcomes in heart failure and reduced ejection fraction (HFrEF) patients in sinus rhythm (SR) and atrial fibrillation (AF) adjusting for natriuretic peptide concentration, a powerful prognosticator. METHODS AND RESULTS: Of 13 562 patients from two large HFrEF trials, 10 113 (74.6%) were in SR and 3449 (25.4%) in AF. The primary endpoint was the composite of cardiovascular death or heart failure hospitalization. Heart rate was analysed as a categorical (tertiles, T1-3) and continuous variable (per 10 bpm), separately in patients in SR and AF. Outcomes were adjusted for prognostic variables, including N-terminal prohormone of B-type natriuretic peptide (NT-proBNP), and also examined using change from baseline heart rate to 1 year (≤ -10 bpm, ≥ +10 bpm, < ±10 bpm). SR patients with a higher heart rate had worse symptoms and quality of life, more often had diabetes and higher NT-proBNP concentrations. They had higher risk of the primary endpoint [T3 vs. T1 adjusted hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.35-1.66; P < 0.001; per 10 bpm: 1.12, 95% CI 1.09-1.16; P < 0.001]. In SR, heart rate was associated with a relatively higher risk of pump failure than sudden death (adjusted HR per 10 bpm 1.17, 95% CI 1.09-1.26; P < 0.001 vs. 1.07, 95% CI 1.02-1.13; P = 0.011). Heart rate was not predictive of any outcome in AF. CONCLUSIONS: In HFrEF, an elevated heart rate was an independent predictor of adverse cardiovascular outcomes in patients in SR, even after adjustment for NT-proBNP. There was no relationship between heart rate and outcomes in AF. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifiers NCT01035255 and NCT00853658.

Left Atrial Function after Atrial Fibrillation Cryoablation Concomitant to Minimally Invasive Mitral Valve Repair: A Pilot Study on Long-Term Results and Clinical Implications.

Background and Objectives: Surgical atrial fibrillation (AF) ablation concomitant to minimally invasive mitral valve repair has been proven to offer improved short- and long-term sinus rhythm (SR) maintenance compared to mitral valve surgery only. The objective of the present study was to explore, by thorough echocardiographic assessment, long-term morphological and functional left atrial (LA) outcomes after this combined surgical procedure. Materials and Methods: From October 2006 to November 2015, 48 patients underwent minimally invasive mitral valve repair and concomitant surgical AF cryoablation. Results: After 3.8 ± 2.2 years, 30 (71.4%) of those completing the follow-up (n = 42, 87.5%) presented SR. During follow-up, four (9.5%) patients suffered from cerebrovascular accidents and two of these subjects had a long-standing persistent AF relapse and were in AF at the time of the event, while the other two were in SR. An echocardiographic study focused on LA characteristics was performed in 29 patients (69.0%). Atrial morphology and function (e.g., maximal LA volume indexed to body surface area and total LA emptying fraction derived from volumes) in patients with stable SR (60.6 ± 13.1 mL/mq and 25.1 ± 7.3%) were significantly better than in those with AF relapses (76.8 ± 16.2 mL/mq and 17.5 ± 7.4%; respectively, p = 0.008 and p = 0.015). At follow-up, patients who suffered from ischemic cerebral events had maximal LA volume indexed to body surface area 61 ± 17.8 mL/mq, with total LA emptying fraction derived from volumes 23.6 ± 13.7%; patients with strokes in SR showed very enlarged LA volume (>70 mL/mq). Conclusions: AF cryoablation concomitant with minimally invasive mitral valve repair provides a high rate of SR maintenance and this relates to improved long-term morphological and functional LA outcomes. Further prospective studies are needed to define the cut-off values determining an increase in the risk for thromboembolic complications in patients with restored stable SR.