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Abstract Cardiac physiologic pacing (CPP), encompassing cardiac resynchronization therapy (CRT) and conduction system pacing (CSP), has emerged as a pacing therapy strategy that may mitigate or prevent the development of heart failure (HF) in patients with ventricular dyssynchrony or pacing‐induced cardiomyopathy. This clinical practice guideline is intended to provide guidance on indications for CRT for HF therapy and CPP in patients with pacemaker indications or HF, patient selection, pre‐procedure evaluation and preparation, implant procedure management, follow‐up evaluation and optimization of CPP response, and use in pediatric populations. Gaps in knowledge, pointing to new directions for future research, are also identified.

BackgroundThe presence of tricuspid regurgitation (TR) is very common in patients with concomitant left-sided valve disease. Recent studies have advocated an additional grading of massive TR that is beyond severe. The present study sought to characterize the spectrum of TR in patients undergoing tricuspid annuloplasty (TA) and to evaluate the prognostic value of TR severity for post-operative outcome following TA.MethodsA total of 176 patients who underwent TA with combined left-sided valve surgery, secondary to rheumatic valvular heart disease, were prospectively evaluated. The severity of TR was quantified by effective regurgitant orifice area (EROA) using the proximal isovelocity surface area method. Patients were categorized as having non-massive TR (EROA < 0.6 cm2) or massive TR (EROA ≥ 0.6 cm2). Adverse outcome was defined as all-cause mortality or heart failure requiring hospital admission following TA.ResultsA total of 55 (31%) patients were considered to have massive TR. Patients with massive TR had a greater right ventricular dimension but a smaller left ventricular dimension compared with those with non-massive TR. After a median follow-up of 39 months, 35 adverse events occurred. Cox-regression analysis showed that both continuous EROA and dichotomized EROA (massive vs. non-massive TR) were independently associated with adverse events even after multivariable adjustment. Further, Harrell C index demonstrated that the addition of massive TR provided better discrimination ability of a prediction model to known prognosticators following TA.ConclusionsMassive TR is common and up to 31% of study population had massive TR. Massive TR was associated with adverse outcome in patients undergoing TA. Classification of the severity of TR by quantitative measures and identification of massive TR in patients with concomitant left-sided valve disease are essential when considering the optimal timing of corrective surgery.

Abstract Background The prognostic implication of statin in tolerance (SI) in those with stable CAD remains unclear. We hypothesized that SI is of higher prognostic significance in stable CAD patients with elevated high-sensitive cardiac troponin I (hs-cTnI). Methods A total of 952 stable CAD patients from the prospective Hong Kong CAD study who had complete clinical data, biomarker measurements and who were prescribed statin therapy were studied. Results We identified 13 (1.4%) and 125 (13.1%) patients with complete and partial SI, respectively. At baseline, patients with SI were more likely to have diabetes mellitus and a higher hs-cTnI level, but no difference in LDL-C level compared with those without SI. After 51 months of follow-up, patients with SI had a higher mean LDL-C level than those without SI. A total of 148 (15.5%) patients developed major adverse cardiovascular events (MACEs). Both SI (HR 1.52, 95% CI 1.06–2.19, P = 0.02) and elevated hs-cTnI (HR 3.18, 95% CI 2.07–4.89, P

The Editors’ Network of the European Society of Cardiology (ESC) provides a dynamic forum for editorial discussions and endorses the recommendations of the International Committee of Medical Journal Editors (ICMJE) to improve the scientific quality of biomedical journals. Authorship confers credit and important academic rewards. Recently, however, the ICMJE emphasized that authorship also requires responsibility and accountability. These issues are now covered by the new (fourth) criterion for authorship. Authors should agree to be accountable and ensure that questions regarding the accuracy and integrity of the entire work will be appropriately addressed. This review discusses the implications of this paradigm shift on authorship requirements with the aim of increasing awareness on good scientific and editorial practices. Keywords: Editorial ethics, Scientific Process, Authorship, Accountability, Scientific journals, Journals

The Editors' Network of the European Society of Cardiology (ESC) provides a dynamic forum for editorial discussions and endorses the recommendations of the International Committee of Medical Journal Editors (ICMJE) to improve the scientific quality of biomedical journals. Authorship confers credit and important academic rewards. Recently, however, the ICMJE emphasized that authorship also requires responsibility and accountability. These issues are now covered by the new (fourth) criterion for authorship. Authors should agree to be accountable and ensure that questions regarding the accuracy and integrity of the entire work will be appropriately addressed. This review discusses the implications of this paradigm shift on authorship requirements with the aim of increasing awareness on good scientific and editorial practices.

BackgroundA high proportion of COVID-19 patients were reported to have cardiac involvements. Data pertaining to cardiac sequalae is of urgent importance to define subsequent cardiac surveillance.MethodsWe performed a systematic cardiac screening for 97 consecutive COVID-19 survivors including electrocardiogram (ECG), echocardiography, serum troponin and NT-proBNP assay 1-4 weeks after hospital discharge. Treadmill exercise test and cardiac magnetic resonance imaging (CMR) were performed according to initial screening results.ResultsThe mean age was 46.5 ± 18.6 years; 53.6% were men. All were classified with non-severe disease without overt cardiac manifestations and did not require intensive care. Median hospitalization stay was 17 days and median duration from discharge to screening was 11 days. Cardiac abnormalities were detected in 42.3% including sinus bradycardia (29.9%), newly detected T-wave abnormality (8.2%), elevated troponin level (6.2%), newly detected atrial fibrillation (1.0%), and newly detected left ventricular systolic dysfunction with elevated NT-proBNP level (1.0%). Significant sinus bradycardia with heart rate below 50 bpm was detected in 7.2% COVID-19 survivors, which appeared to be self-limiting and recovered over time. For COVID-19 survivors with persistent elevation of troponin level after discharge or newly detected T wave abnormality, echocardiography and CMR did not reveal any evidence of infarct, myocarditis, or left ventricular systolic dysfunction.ConclusionCardiac abnormality is common amongst COVID-survivors with mild disease, which is mostly self-limiting. Nonetheless, cardiac surveillance in form of ECG and/or serum biomarkers may be advisable to detect more severe cardiac involvement including atrial fibrillation and left ventricular dysfunction.

Abstract Atrioventricular nodal (AVN) ablation and right ventricular (RV) pacing is recommended for refractory atrial fibrillation (AF) and tachycardia‐bradycardia syndrome. Three AF patients (mean age 83, range 79‐89 years) underwent AVN ablation and transvenous leadless pacemaker Micra™ implantations using the same venous access without anticoagulation interruption. Satisfactory pacing 0.59 (0.50‐0.63) V at 0.24 ms and sensing 11.2 (6.3‐15.6) mV were achieved within 1‐3 deployments. There were no vascular complications nor device dislodgment. Durable pacemaker parameters and VVIR pacing were achieved. Combined AVN ablation and leadless pacemaker implantation is feasible and safe, and avoids pacemaker pocket hematoma and bleeding complications in patients on uninterrupted anticoagulation.

Abstract Background Whether PR prolongation independently predicts new-onset ischemic events of myocardial infarction and stroke was unclear. Underlying pathophysiological mechanisms of PR prolongation leading to adverse cardiovascular events were poorly understood. We investigated the role of PR prolongation in pathophysiologically-related adverse cardiovascular events and underlying mechanisms. Methods We prospectively investigated 597 high-risk cardiovascular outpatients (mean age 66 ± 11 yrs.; male 67%; coronary disease 55%, stroke 22%, diabetes 52%) for new-onset ischemic stroke, myocardial infarction (MI), congestive heart failure (CHF), and cardiovascular death. Vascular phenotype was determined by carotid intima-media thickness (IMT). Results PR prolongation >200 ms was present in 79 patients (13%) at baseline. PR prolongation >200 ms was associated with significantly higher mean carotid IMT (1.05 ± 0.37 mm vs 0.94 ± 0.28 mm, P = 0.010). After mean study period of 63 ± 11 months, increased PR interval significantly predicted new-onset ischemic stroke (P = 0.006), CHF (P = 0.040), cardiovascular death (P 200 ms. Using multivariable Cox regression, PR prolongation >200 ms independently predicted new-onset ischemic stroke (HR 8.6, 95% CI: 1.9–37.8, P = 0.005), cardiovascular death (HR 14.1, 95% CI: 3.8–51.4, P 162 ms (C-statistic 0.70, P = 0.001; HR: 8.0, 95% CI: 1.65–38.85, P = 0.010). Conclusions PR prolongation strongly predicts new-onset ischemic stroke, MI, cardiovascular death, and combined cardiovascular endpoint including CHF in coronary patients or risk equivalent. Adverse vascular function may implicate an intermediate pathophysiological phenotype or mediating mechanism.

The International Committee of Medical Journal Editors (ICMJE) provides recommendations to improve the editorial standards and scientific quality of biomedical journals. These recommendations range from uniform technical requirements to more complex and elusive editorial issues including ethical aspects of the scientific process. Recently, registration of clinical trials, conflicts of interest disclosure, and new criteria for authorship -emphasizing the importance of responsibility and accountability-, have been proposed. Last year, a new editorial initiative to foster sharing of clinical trial data was launched. This review discusses this novel initiative with the aim of increasing awareness among readers, investigators, authors and editors belonging to the Editors’ Network of the European Society of Cardiology.

The International Committee of Medical Journal Editors (ICMJE) provides recommendations to improve the editorial standards and scientific quality of biomedical journals. These recommendations range from uniform technical requirements to more complex and elusive editorial issues including ethical aspects of the scientific process. Recently, registration of clinical trials, conflicts of interest disclosure, and new criteria for authorship -emphasizing the importance of responsibility and accountability-, have been proposed. Last year, a new editorial initiative to foster sharing of clinical trial data was launched. This review discusses this novel initiative with the aim of increasing awareness among readers, investigators, authors and editors belonging to the Editors’ Network of the European Society of Cardiology.

Ictal asystole due to sinus node suppression is a cause of sudden unexplained death in epilepsy. Here, for the first time, we describe a complete atrioventricular nodal block in a patient with non-compressive traumatic subdural hematoma, who developed ictal asystole as a delayed presentation. A leadless VVI pacemaker (ventricular paced, ventricular sensed, and pacing inhibited in response to a sensed beat) was implanted as a preventive measure against seizure-related heart block.

BackgroundTricuspid annuloplasty is increasingly performed during left heart valve surgery, but the long‐term clinical outcome postoperatively is not satisfactory. The aim of this study was to determine whether residual pulmonary hypertension (PHT) contributes to the adverse outcome. Methods and ResultsOne‐hundred thirty‐seven patients (age 61±11 years; men, 30%) who underwent tricuspid annuloplasty during left‐side valve surgery were enrolled. The mean pulmonary artery systolic pressure before surgery was 49±13 mm Hg and 32±15 mm Hg following surgery. Patients were divided into 3 groups according to postoperative pulmonary artery systolic pressure: no residual PHT (n=78, 57%), mild residual PHT (n=43, 31%), or significant residual PHT (n=16, 12%). A preoperative larger right ventricular (RV) geometry and tricuspid valve tethering area were associated with mild or significant residual PHT. A total of 24 adverse events (20 heart failures and 4 cardiovascular deaths) occurred during a median follow‐up of 25 months. Kaplan–Meier survival curve demonstrated that patients with significant residual PHT had the highest percentage of adverse events followed by those with mild residual PHT. Patients with no residual PHT had a very low risk of adverse events. Multivariable Cox regression analysis revealed that both mild (hazard ratio=4.94; 95% CI =1.34–18.16; P=0.02) and significant residual PHT (hazard ratio=8.67; 95% CI =2.43–30.98; P

AIM:Heart failure (HF) increases the risk of thromboembolic events (TE). Study in a Caucasian population has shown that the CHA2DS2-VASc score predicts TE among HF patients without atrial fibrillation. We sought to assess the usefulness of the CHA2DS2-VASc score in predicting TE in an Asian population and refine the scoring system to improve its predictability of TE among HF patients in sinus rhythm. METHODS:A total of 1,202 consecutive patients who were admitted to our institution for new-onset HF from 2005 to 2012 and without atrial fibrillation or anticoagulation were retrospectively reviewed. RESULTS:The mean age was 77.6 ± 12.2 years and 51.7% were female. After 36.2 ± 30.1 months, 113 (9.4%) developed TE. The annual incidence was 0.54%, 1.54%, 2.98% and 5.04% per year in those who had a CHA2DS2-VASc score of 1, 2-3, 4-5 and ≥6, respectively. In multivariate analysis, age ≥75 years [Hazard ratio (HR) 2.59, 95% confidence interval (CI) 1.23-5.46, p = 0.012), chronic ischemic heart disease (HR 1.54, 95% CI 1.02-2.31, p = 0.040) and chronic kidney disease (HR 1.66, 95% CI 1.09-2.53, p = 0.018) independently predicted TE. Incorporation of chronic ischemic heart disease and chronic kidney disease into the CHA2DS2-VASc score significantly increased the area under the Receiver Operating Curve from 0.57 (95% CI 0.54-0.59) to 0.61 (95% CI 0.55-0.66; p = 0.022). CONCLUSION:The CHA2DS2-VASc score is useful for stratification of the risk of TE among HF patients in sinus rhythm. Incorporation of chronic ischemic heart disease and chronic kidney disease into the score modestly improves its predictive value.

Disclosure of potential conflicts of interest (COI) is used by biomedical journals to guarantee credibility and transparency of the scientific process. Conflict of interest disclosure, however, is not systematically nor consistently dealt with by journals. Recent joint editorial efforts paved the way towards the implementation of uniform vehicles for COI disclosure. This paper provides a comprehensive editorial perspective on classical COI-related issues. New insights into the current COI policies and practices among European Society of Cardiology National Cardiovascular Journals, as derived from a cross-sectional survey using a standardised questionnaire, are discussed. Keywords: Conflict of interest, Disclosure, Editorial ethics, Journals

Heart failure (HF)-related hospitalization is associated with significant mortality and morbidity and can be prevented by early intervention. Implantable sensors detect early pathophysiological changes in HF, using an accelerometer, a paced electrogram, impedance and pressure sensors in implanted intracardiac leads, or stand-alone devices. Such sensors monitor daily activity, QT and ST intervals, pulmonary fluid, and intracardiac pressures at various points. Sensor data are available either by patient's or physician's regular interrogation, or using remote patient monitoring. Different sensors have different levels of sensitivity and specificity for HF detection, and they have the ability to antedate HF exacerbation and thereby allow for the initiation of intervention to avert decompensation. Clinical studies suggest that alone or in combination, such sensors have a greater beneficial impact than conventional therapy on acute HF outcome.

BACKGROUND: Although fibroblast-to-myocyte electrical coupling is experimentally suggested, electrophysiology of cardiac fibroblasts is not as well established as contractile cardiac myocytes. The present study was therefore designed to characterize ion channels in cultured human cardiac fibroblasts. METHODS AND FINDINGS: A whole-cell patch voltage clamp technique and RT-PCR were employed to determine ion channels expression and their molecular identities. We found that multiple ion channels were heterogeneously expressed in human cardiac fibroblasts. These include a big conductance Ca(2+)-activated K(+) current (BK(Ca)) in most (88%) human cardiac fibroblasts, a delayed rectifier K(+) current (IK(DR)) and a transient outward K(+) current (I(to)) in a small population (15 and 14%, respectively) of cells, an inwardly-rectifying K(+) current (I(Kir)) in 24% of cells, and a chloride current (I(Cl)) in 7% of cells under isotonic conditions. In addition, two types of voltage-gated Na(+) currents (I(Na)) with distinct properties were present in most (61%) human cardiac fibroblasts. One was a slowly inactivated current with a persistent component, sensitive to tetrodotoxin (TTX) inhibition (I(Na.TTX), IC(50) = 7.8 nM), the other was a rapidly inactivated current, relatively resistant to TTX (I(Na.TTXR), IC(50) = 1.8 microM). RT-PCR revealed the molecular identities (mRNAs) of these ion channels in human cardiac fibroblasts, including KCa.1.1 (responsible for BK(Ca)), Kv1.5, Kv1.6 (responsible for IK(DR)), Kv4.2, Kv4.3 (responsible for I(to)), Kir2.1, Kir2.3 (for I(Kir)), Clnc3 (for I(Cl)), Na(V)1.2, Na(V)1.3, Na(V)1.6, Na(V)1.7 (for I(Na.TTX)), and Na(V)1.5 (for I(Na.TTXR)). CONCLUSIONS: These results provide the first information that multiple ion channels are present in cultured human cardiac fibroblasts, and suggest the potential contribution of these ion channels to fibroblast-myocytes electrical coupling.

Introduçao: Pacientes idosos, portadores de marcapasso e com incompetência cronotrópica (IC) podem apresentar hipotensao em posiçao ortostática (HO). Objetivo: Determinar se o aumento transitório da freqüência cardíaca, por meio da opçao de programaçao rate drop response (resposta à queda da freqüência cardíaca), previne a HO em pacientes idosos, portadores de marcapasso, em posiçao vertical. Casuística e Método: Foram estudados os efeitos da rate drop response para alívio da queda da pressao arterial em 62 pacientes portadores de marcapasso (77 ± 6 anos, 32 F) em posiçao vertical. O modo de comando foi o de dupla-câmara (DDD) e as indicaçoes para o implante foram doença do nodo sinusal (n=40) ou bloqueio atrioventricular (n=22). Todos os pacientes foram submetidos a dois procedimentos na posiçao ereta, em ordem aleatória: controle com freqüência básica de 60 bpm e com rate drop response no modo DDD (com possibilidade de aumento de 35 bpm acima da freqüência de base), durante 2 minutos, após ficarem na posiçao vertical. A pressao arterial sistólica (PAS), a pressao arterial diastólica (PSD) e a freqüência cardíaca foram aferidas na posiçao vertical (linha de base) e um, dois e três minutos após o abandono dessa posiçao. A HO foi definida como uma queda da pressao arterial sistólica (PAS) ≥ 20 mmHg ou da pressao arterial diastólica (PSD) ≥ 10 mmHg, em posiçao vertical. A incompetência cronotrópica (IC) foi definida como ausência de aumento da freqüência cardíaca superior a 10 bpm, enquanto na posiçao de pé. Resultados: Um total de 17 pacientes (27%) desenvolveu HO na posiçao em pé. As características clínicas básicas (idade, sexo, prevalência de diabetes, uso de medicamentos vasoativos e doença do nodo sinusal) foram similares nos dois grupos, com ou sem HO. Na posiçao vertical, o rate drop response aumentou a PAS e PSD, em comparaçao com a linha de base (PConclusao: A HO é comum e está presente em 27% da populaçao idosa portadora de marcapasso. Em apenas um subgrupo desses pacientes, a IC pode ser a responsável pela ocorrência de HO e pode ser prevenida pela rate drop response na posiçao vertical.