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Precise localization of the site of origin of premature ventricular contractions (PVCs) before ablation can facilitate the planning and execution of the electrophysiological procedure.The purpose of this study was to develop a predictive model that can be used to differentiate PVCs between the left ventricular outflow tract and right ventricular outflow tract (RVOT) using surface electrocardiogram characteristics.A total of 851 patients undergoing radiofrequency ablation of premature ventricular beats from January 2015 to March 2022 were enrolled. Ninety-two patients were excluded. The other 759 patients were enrolled into the development (n = 605), external validation (n = 104), or prospective cohort (n = 50). The development cohort consisted of the training group (n = 423) and the internal validation group (n = 182). Machine learning algorithms were used to construct predictive models for the origin of PVCs using body surface electrocardiogram features.In the development cohort, the Random Forest model showed a maximum receiver operating characteristic curve area of 0.96. In the external validation cohort, the Random Forest model surpasses 4 reported algorithms in predicting performance (accuracy 94.23%; sensitivity 97.10%; specificity 88.57%). In the prospective cohort, the Random Forest model showed good performance (accuracy 94.00%; sensitivity 85.71%; specificity 97.22%).Random Forest algorithm has improved the accuracy of distinguishing the origin of PVCs, which surpasses 4 previous standards, and would be used to identify the origin of PVCs before the interventional procedure.

BackgroundNew-onset atrial fibrillation (NeAF) is common after cavotricuspid isthmus-dependent counterclockwise atrial flutter (CCW-AFL) ablation. This study aimed to investigate a simple predictive model of NeAF after CCW-AFL ablation.Methods and ResultsFrom January 2013 to December 2017, consecutive patients receiving CCW-AFL ablation were enrolled from three centers. Clinical, echocardiographic, and electrocardiographic data were collected and followed. Patients from two centers and another center were assigned into the derivation and validation cohorts, respectively. In the derivation cohort, logistic regression was performed to evaluate the ability of parameters to discriminate those with and without NeAF. A score system was developed and then validated. Two hundred seventy-one patients (mean 59.7±13.6 age; 205 male) were analyzed. During follow-up (73.0±6.5 months), 107 patients (39.5%) had NeAF. 190 and 81 patients were detected in the derivation and validation cohorts, respectively. Hypertension, age ≥70 years, left atrial diameter ≥42 mm, P wave duration ≥120 ms and the negative component of flutter wave in lead II ≥120 ms were selected as the final parameters. A weighted score was used to develop the HAD-AF score ranging from 0 to 9. In the derivation cohort, area under the receiver operating characteristic curve (AUC) was 0.938 (95% CI 0.902-0.974), superior to those of currently used CHA2DS2-VASC(0.679, 95% CI 0.600-0.757) and HATCH scores (0.651, 95% CI 0.571-0.730) (PConclusions39.5% of patients developed NeAF in 6 years after CCW-AFL ablation. HAD-AF score can reliably identify patients likely to develop NeAF after CCW-AFL ablation.Clinical PerspectiveWhat Is New?During a follow-up period of more than 6 years after CCW-AFL ablation, 107 of 271 (39.5%) patients developed NeAF.HAD-AF score, based on easily obtainable clinical, echocardiographic and electrocardiographic parameters, could better predict development of NeAF after CCW-AFL ablation (area under the receiver operating characteristics curve [AUC], 0.938), compared with currently used HATCH score (AUC, 0.651) and CHA2DS2-VASCscore (AUC, 0.679) (PWhat Are the Clinical Implications?In CCW-AFL patients with a HAD-AF score >4, close postoperative follow-up for earlier detection of AF should be recommended, or the option of concomitant AF ablation could be considered during the shared decision-making process.

Remote monitoring is beneficial for the management of patients with cardiovascular implantable electronic devices by impacting morbidity and mortality. With increasing numbers of patients using remote monitoring, keeping up with higher volume of remote monitoring transmissions creates challenges for device clinic staff. This international multidisciplinary document is intended to guide cardiac electrophysiologists, allied professionals, and hospital administrators in managing remote monitoring clinics. This includes guidance for remote monitoring clinic staffing, appropriate clinic workflows, patient education, and alert management. This expert consensus statement also addresses other topics such as communication of transmission results, use of third-party resources, manufacturer responsibilities, and programming concerns. The goal is to provide evidence-based recommendations impacting all aspects of remote monitoring services. Gaps in current knowledge and guidance for future research directions are also identified.

The association of obstructive sleep apnea (OSA) with bradycardia is not well-characterized, which may confer significant morbidity and mortality if left untreated. We sought to clarify the prevalence of comorbid OSA and bradycardia, and the effect of continuous positive airway pressure (CPAP) therapy on bradycardia outcomes.We systematically searched four electronic databases (PubMed, Embase, Cochrane Library, Scopus) for randomized or observational studies reporting the co-prevalence of sleep apnea and bradycardia or evaluated the use of CPAP on the incidence of bradycardias. We used random-effects models in all meta-analyses and evaluated heterogeneity using IWe included 34 articles from 7204 records, comprising 4852 patients. Among patients with OSA, the pooled prevalence of daytime and nocturnal bradycardia were 25% (95% CI: 18.6 to 32.7) and 69.8% (95% CI: 41.7 to 88.2) respectively. Among patients with bradycardia, the pooled prevalence of OSA was 56.8% (95% CI: 21.5 to 86.3). CPAP treatment, compared to those without, did not significantly reduce the risk of daytime (two randomized trials; RR: 0.50; 95% CI: 0.11 to 2.21) or nocturnal bradycardia (one randomized-controlled trial and one cohort study; RR: 0.76; 95% CI: 0.48 to 1.20).This meta-analysis demonstrates a high comorbid disease burden between OSA and bradycardia. Future research should explore the treatment effect of CPAP on bradycardia incidence, as compared to placebo.

BACKGROUND The Singapore Cardiac Databank was designed to monitor the performance and outcomes of catheter ablation. We investigated the outcomes of paroxysmal supraventricular tachycardia (PSVT)-ablation in a prospective, nationwide, cohort study. METHODS Atrioventricular nodal re-entrant tachycardia (AVNRT), atrioventricular re-entry tachycardia (AVRT) or atrial tachycardia (AT)-ablations in Singapore from 2010 to 2018 were studied. Outcomes include acute success, periprocedural-complications, post-operative pacing requirement, arrhythmic recurrence and one-year all-cause mortality. RESULTS Among 2,260 patients (mean age 45±18years, 50% female, 57% AVNRT, 37% AVRT, 6% AT), overall acute success rates of PSVT-ablation was 98.4% and increased in order of AT, AVRT and AVNRT (p

Aims This study aims to determine procedural characteristics, acute success rates, and medium-term outcomes of consecutive patients undergoing His bundle pacing (HBP); and learning curves of experienced electrophysiologists adopting HBP. Methods and results Consecutive HBP patients at three hospitals were recruited. Clinical characteristics, acute procedural details, and medium-term outcomes were extracted from electronic medical records. Two hundred and thirty-three patients [mean age 74.6 ± 10.1 years, 48% female, 68% narrow QRS, 71% normal left ventricular ejection fraction (LVEF), 55.8% atrioventricular block] underwent HBP. Acute procedural success was 81.1% (mean procedural and fluoroscopic times of 105.5 ± 36.5 and 13.8 ± 9.3 min). Broad QRS was associated with lower HBP success (odds ratio 0.39, P = 0.02). Fluoroscopic and procedural times decreased and plateaued after 30–40 cases per operator. Implant HBP threshold was 1.3 ± 0.7 V at 1.0 ± 0.2 ms and R wave was 5.0 ± 3.9 mV. During follow-up, loss of HBP occurred in a further 12.4% and 11.3% of patients experienced a ≥1 V increase in HBP threshold. Five (2.6%) patients required HBP revision for pacing difficulties. About 8.6% of patients had a >50% decrease in R wave but lead revision for sensing issues was not necessary. On an intention to treat basis, 56.7% of patients in whom HBP was attempted had persisting HBP capture and thresholds of Conclusion Physicians adopting HBP should be cognizant of the learning curve and preferentially select non-dependent patients with normal QRS and LVEF, to minimize risk of lead revision. Further rises in HBP threshold may increase battery drain and need for reoperations, important considerations when choosing HBP for cardiac resynchronization therapy.

Catheter ablation (CA) of atrioventricular nodal reentrant tachycardia (AVNRT) is associated with late pacemakers for AV block (AVB). We performed a systematic review and meta-analysis of the pooled incidence of late pacemakers for AVB after CA of AVNRT.Relevant studies were identified from four electronic databases (PubMed, EMBASE, Scopus, and Cochrane Trial Register) from inception to 2022. A random effects model was used to calculate the odds of late pacemakers in CA of AVNRT compared to atrioventricular reentrant tachycardia (AVRT). Of 533 articles screened, 13 were included in systematic review. CA for AVNRT was performed in 16 471 patients (mean age 54 ± 17 years, 63% females), of which 68 (0.4%) underwent pacemaker implantation for late AVB. Meta-analysis was performed in 5 of the 13 studies (mean follow-up duration 7 ± 4 years). Patients who underwent CA of AVNRT were older (58 ± 17 vs. 52 ± 20 years, p .001), and more likely female (60% vs. 41%, p .001) than AVRT. Pooled estimates of late pacemakers for AVB were higher in CA of AVNRT than AVRT (0.5% vs. 0.2%, p = .006), with CA in AVNRT associated with almost twofold increased odds of late pacemakers indicated for AVB (odds ratio: 1.94, 95% confidence interval: 1.08-3.47, p = .027) compared to AVRT.AVNRT ablation is safe but associated with a low but definitely increased risk of requiring pacing in the later years due to AVB. This association is confirmed by pooling over 16 000 AVNRT patients receiving clinically indicated ablation and is helpful in providing informed consent for prospective patients undergoing ablation for AVNRT.

BACKGROUND: Little is known about the effect of the coronavirus disease 2019 (COVID-19) pandemic and the outbreak response measures on door-to-balloon time (D2B). This study examined both D2B and clinical outcomes of patients with STEMI undergoing primary percutaneous coronary intervention (PPCI).Methods and Results:This was a retrospective study of 303 STEMI patients who presented directly or were transferred to a tertiary hospital in Singapore for PPCI from October 2019 to March 2020. We compared the clinical outcomes of patients admitted before (BOR) and during (DOR) the COVID-19 outbreak response. The study outcomes were in-hospital death, D2B, cardiogenic shock and 30-day readmission. For direct presentations, fewer patients in the DOR group achieved D2B time

The relative and combined effects of sleep apnea with diabetes mellitus (DM) on cardiovascular outcomes in patients undergoing coronary artery bypass grafting (CABG) remain unknown. In this secondary analysis of data from the SABOT study, 1007 patients were reclassified into four groups based on their sleep apnea and DM statuses, yielding 295, 218, 278, and 216 patients in the sleep apnea (+) DM (+), sleep apnea (+) DM (−), sleep apnea (−) DM (+), and sleep apnea (−) DM (−) groups, respectively. After a mean follow-up period of 2.1 years, the crude incidence of major adverse cardiac and cerebrovascular event was 18% in the sleep apnea (+) DM (+), 11% in the sleep apnea (+) DM (−), 13% in the sleep apnea (−) DM (+), and 5% in the sleep apnea (−) DM (−) groups. Using sleep apnea (−) DM (−) as the reference group, a Cox regression analysis indicated that sleep apnea (+) and DM (+) independently predicted MACCEs (adjusted hazard ratio, 3.2; 95% confidence interval, 1.7–6.2; p = 0.005) and hospitalization for heart failure (adjusted hazard ratio, 12.6; 95% confidence interval, 3.0–52.3; p Clinical trial registration: ClinicalTrials.gov identification no. NCT02701504.

ObjectivePatients with advanced coronary artery disease are referred for coronary artery bypass grafting (CABG) and it remains unknown if sleep apnoea is a risk marker. We evaluated the association between sleep apnoea and major adverse cardiac and cerebrovascular events (MACCE) in patients undergoing non-emergent CABG.MethodsThis was a prospective cohort study conducted between November 2013 and December 2018. Patients from four public hospitals referred to a tertiary cardiac centre for non-emergent CABG were recruited for an overnight sleep study using a wrist-worn Watch-PAT 200 device prior to CABG.ResultsAmong the 1007 patients who completed the study, sleep apnoea (defined as apnoea-hypopnoea index ≥15 events per hour) was diagnosed in 513 patients (50.9%). Over a mean follow-up period of 2.1 years, 124 patients experienced the four-component MACCE (2-year cumulative incidence estimate, 11.3%). There was a total of 33 cardiac deaths (2.5%), 42 non-fatal myocardial infarctions (3.7%), 50 non-fatal strokes (4.9%) and 36 unplanned revascularisations (3.2%). The crude incidence of MACCE was higher in the sleep apnoea group than the non-sleep apnoea group (2-year estimate, 14.7% vs 7.8%; p=0.002). Sleep apnoea predicted the incidence of MACCE in unadjusted Cox regression analysis (HR 1.69; 95% CI 1.18 to 2.43), and remained statistically significant (adjusted HR 1.57; 95% CI 1.09 to 2.25), after adjustment for age, sex, body mass index, left ventricular ejection fraction, diabetes mellitus, hypertension, chronic kidney disease and excessive daytime sleepiness.ConclusionSleep apnoea is independently associated with increased MACCE in patients undergoing CABG.Trial registration numberNCT02701504

Optimal left ventricular (LV) lead placement improves response to cardiac resynchronization therapy (CRT) but can be hindered by unfavorable venous anatomy. Interventional procedures in the coronary veins have been described with promising short-term outcomes.The purpose of this study was to establish the safety and efficacy of percutaneous coronary venoplasty (PCV) during CRT implantation and assess medium-term lead performances and clinical outcomes against matched controls not requiring PCV.Each consecutive PCV case was matched according to age, gender, and bundle branch morphology to 2 controls from a large prospective registry of CRT recipients. Demographics, procedural success, lead performance, and response to CRT were tracked using a comprehensive electronic medical records system.Of 422 consecutive CRT recipients treated between 2012 to 2018, 29 patients (6.9%; mean age 65.7 ± 10.7 years; 7 female; 17 ischemic cardiomyopathy; 22 left bundle branch block) required PCV, which was successful in 21 cases (72%). Target veins measuring 1.1 ± 0.6 mm were dilated by noncompliant balloons with mean diameter 2.8 ± 0.5 mm. No complications occurred. Fluoroscopic and procedural durations were longer in the PCV group (P.01) Over mean follow-up of 33.0 ± 25.0 months, no differences in lead performance, CRT response, or 2-year survival were observed compared to the control group.PCV during CRT device implant is typically successful, safe and associated with long-term clinical outcomes comparable to patients who did not need PCV. This is an important technique to optimize LV lead placement and maximize CRT response.

Obstructive sleep apnea (OSA) during the rapid eye movement (REM) stage of the sleep cycle is associated with intense hypoxemia and cardiovascular instability. We characterized OSA during REM sleep in patients after percutaneous coronary intervention. In this multicenter study, 204 patients who had undergone percutaneous coronary intervention in the prior 6 to 36 months were recruited for in-laboratory polysomnography. The primary measure was respiratory events during REM sleep. The patients were divided into 2 groups: (1) OSA during REM sleep (≥ 15 events/h) and (2) absence of OSA during REM sleep (

Conventional unipolar catheter ablation (UA) is generally effective for the treatment of outflow tract ventricular arrhythmias (OT-VAs). However, deep foci refractory to UA remains a clinical challenge. The present study evaluated the efficacy and safety of bipolar ablation (BA) in the treatment of OT-VAs refractory to UA.A total of 1022 consecutive patients with antiarrhythmic drugs resistant OT-VAs were screened for inclusion in this study, from 1643 VAs cases who underwent catheter ablation in two centers from October 2014 to May 2019. BA was performed after failed sequential UA. The pair of catheters used for BA was positioned on opposing surfaces of the earliest activation (EA) sites or on adjacent anatomical structures.Twelve patients (seven males, mean age 33.3 ± 16.2 years) who met the inclusion criteria were recruited: one patient suffered sustained monomorphic ventricular tachycardia (VT), six patients had frequent premature ventricular contractions (PVCs), and nonsustained VT (NSVT), and five patients had PVCs only. The 24-hPVC/NSVT burden was 36.9 ± 21.7%. The mean distance between two ablation catheters during BA was 11.1 ± 4.3 mm (range 6.5-23.9 mm). The "rS" morphology of the unipolar electrogram was recorded simultaneously in both EA regions in seven cases (58.3%). Acute eradication of VAs was obtained in 10 (83.3%) cases. At a median follow-up of 58 months, 10 patients (83.3%) remained free from VAs.BA was highly effective and safe for the treatment of OT-VAs refractory to UA.

Pacing leads with extendable-retractable helix (EHL) are alternatives to fixed-helix leads (FHL) for conduction system pacing (CSP), but data on handling characteristics are limited. This study evaluated a dual-center experience of lead handling and performance during CSP.Consecutive patients with His-bundle pacing (HBP) or left bundle branch pacing (LBBP) were evaluated for the primary outcome of lead failure, defined as structural damage to the lead necessitating lead replacement. Differences in pacing characteristics were compared. Among 280 patients (mean age 74 ± 11 years, 44% male, 50% LBBP), 246 (88%) received FHL and 34 (12%) received EHL. Of 299 leads used, lead failure occurred more frequently among patients with EHL than FHL (29% vs. 2%, p .001), regardless of CSP modality. Majority of damaged leads (89%) in the form of helix deformation were successfully removed, with failure occurring in only two patients, both EHL, leading to helix fracture and retention within the septal myocardium. EHL, compared to FHL, was associated with 25-fold increased odds of lead failure (odds ratio: 25.21, 95% confidence interval: 7.35-86.51), and persisted after adjustment in turn for age, pacing modality and indication. CSP implant success rates did not differ by lead design (FHL 80% vs. EHL 71%, p = .18), with similar pacing thresholds at implant and follow-up.Helix deformation and fracture were more frequent with EHL in CSP despite similar implant success. These findings have significant implications for lead selection during CSP and raises concerns about the long-term extractability of EHL in CSP.

Obstructive sleep apnoea (OSA) is strongly associated with cardiovascular disease (CVD). However, evidence supporting this association in the Asian population is scarce. Given the differences in the epidemiology of CVD and cardiovascular risk factors, as well as differences in the availability of healthcare resources between Asian and Western countries, an Asian Pacific Society of Cardiology (APSC) working group developed consensus recommendations on the management of OSA in patients with CVD in the Asia-Pacific region. The APSC expert panel reviewed and appraised the available evidence using the Grading of Recommendations Assessment, Development, and Evaluation system. Consensus recommendations were developed and put to an online vote. Consensus was reached when 80% of votes for a given recommendation were in support of ‘agree’ or ‘neutral.’ The resulting statements provide guidance on the assessment and treatment of OSA in patients with CVD in the Asia-Pacific region. The APSC hopes for these recommendations to pave the way for screening, early diagnosis and treatment of OSA in the Asia-Pacific region.

BackgroundChest pain (CP) accounts for 5% of emergency department (ED) visits, unplanned hospitalisations and costly admissions. Conversely, outpatient evaluation requires multiple hospital visits and longer time to complete testing. Rapid access chest pain clinics (RACPCS) are established in the UK for timely, cost-effective CP assessment. This study aims to evaluate the feasibility, safety, clinical and economic benefits of a nurse-led RACPC in a multiethnic Asian country.MethodsConsecutive CP patients referred from a polyclinic to the local general hospital were recruited. Referring physicians were left to their discretion to refer patients to the ED, RACPC (launched in April 2019) or outpatients. Patient demographics, diagnostic journey, clinical outcomes, costs, HEART (History, ECG, Age, Risk Factors, Troponin) scores and 1-year overall mortality were recorded.Results577 CP patients (median HEAR score of 2.0) were referred; 237 before the launch of RACPC. Post RACPC, fewer patients were referred to the ED (46.5% vs 73.9%, pConclusionsAn Asian nurse-led RACPC expedited specialist evaluation of CP with less visits, reduced ED attendances and invasive testing whilst saving costs. Wider implementation across Asia would significantly improve CP evaluation.

STUDY OBJECTIVES: Sleep apnea is prevalent in patients undergoing coronary artery bypass grafting (CABG). We investigated the relationship between sleep apnea and recurrent heart failure hospitalizations in patients undergoing nonurgent CABG. METHODS: Between November 2013 and December 2018, 1,007 patients completed a sleep study prior to CABG and were followed up until April 2020. Recurrent heart failure hospitalizations were analyzed by Poisson, negative binomial, Andersen–Gill, and joint frailty models, with partial and full adjustment for covariates. RESULTS: At an average follow-up of 3.3 years, the number of patients with 0, 1, or ≥ 2 heart failure hospitalizations were 908 (90.2%), 62 (6.2%), and 37 (3.7%), respectively. The total number of heart failure hospitalizations was 179, comprising 62 (35%) first and 117 (65%) repeat events. The numbers of heart failure hospitalizations for the sleep apnea (n = 513, 50.9%) and nonsleep apnea groups were 127 and 52, respectively. Negative binomial regression demonstrated that sleep apnea was associated with recurrent heart failure hospitalizations (fully adjusted rate ratio, 1.71; 95% confidence interval [CI], 1.12–2.62; P = .013). Similar results were found in Poisson (1.63; 95% CI, 1.15–2.31; P = .006), Andersen–Gill (1.66; 95% CI, 1.01–2.75; P = .047), and joint frailty models (1.72; 95% CI, 1.00–3.01; P = .056) CONCLUSIONS: In patients after CABG, repeat events accounted for two-thirds of heart failure hospitalizations. Sleep apnea was independently associated with recurrent heart failure hospitalizations. CITATION: Teo YH, Tam WT, Koo C-Y, et al. Sleep apnea and recurrent heart failure hospitalizations after coronary artery bypass grafting. J Clin Sleep Med. 2021;17(12):2399–2407.

Cytochrome P4502J2 (CYP2J2) metabolizes arachidonic acid (AA) to cardioprotective epoxyeicosatrienoic acids (EETs). Dronedarone, an antiarrhythmic drug prescribed for treatment of atrial fibrillation (AF) induces cardiac adverse effects (AEs) with poorly understood mechanisms. We previously demonstrated that dronedarone inactivates CYP2J2 potently and irreversibly, disrupts AA-EET pathway leading to cardiac mitochondrial toxicity rescuable

Pulmonary embolism (PE) care has traditionally been fragmented. The newly introduced Pulmonary Embolism Response Team (PERT) model provides streamlined care based on expedient, multi-disciplinary decision-making. This study aimed to quantify the impact of PERT, as part of a hospital-wide PE treatment protocol, on clinical outcomes.Consecutive adult patients with acute PE diagnosed via computed tomography pulmonary angiogram (CTPA) were included. The PERT and treatment protocol were introduced in January 2015. Patient characteristics, therapies, quality measures of CTPA reporting, and clinical outcomes of PE patients treated for 2 years before and after implementation of these changes were evaluated. Primary endpoints were median length of stay in intensive care (ICU) and survival to discharge.A total of 321 consecutive PE patients were enrolled, of which 154 (treated in 2013-2014) and 167 (2015-2016) patients formed the historical control and study groups, respectively. Implementation of the algorithm was associated with less variance in anticoagulation and improved reporting of right heart strain parameters on CTPA. The ICU stay was reduced from a median of 5 to 2 days (p 0.01). Eligible massive PE patients receiving reperfusion increased from 30% to 92% (p = 0.01), with mean delay from diagnosis to reperfusion decreasing from 763 to 181 minutes (p 0.01). Bleeding complications were not increased, but overall survival to discharge remained unchanged.Introducing a PERT and treatment protocol reduced ICU stay, enhanced quality measures, and improved access of massive PE patients to reperfusion therapies, without increasing bleeding complications or health care costs.

BACKGROUND Recurrence rates after catheter radiofrequency ablation (RFA) for arrhythmias arising from deep myocardial substrates can exceed 40%. Failure of RFA is in part due to the inability of widely used unipolar ablation (UA) to create transmural lesions capable of disrupting the critical components of the arrhythmia circuit. A radiofrequency generator was custom-made to deliver bipolar ablation (BA) to test the hypothesis that BA is more effective compared to UA in achieving transmurality and to determine the optimal configuration for ventricular BA. METHODS Sequential UA and BA were created in porcine ventricular septal and free wall preparations using irrigated, contact-force sensing ablation catheters, orientated perpendicularly to the myocardium. Return catheters, durations of ablation, irrigating fluids, and power settings were varied to determine the optimal configuration for BA. Lesion characteristics, transmurality, and occurrence of steam pops were analyzed. RESULTS In both ventricular septal and free wall models, BA resulted in significantly more transmural lesions while causing less steam pops (P

Background: Real world data on clinical outcomes and quality of care for patients with coronary artery disease (CAD) are fragmented. We describe the rationale and design of the Singapore Cardiovascular Longitudinal Outcomes Database (SingCLOUD). Methods and Results: We designed a health data grid to integrate clinical, administrative, laboratory, procedural, prescription and financial data from all public-funded hospitals and primary care clinics, which provide 80% of health care in Singapore. Here, we explain our approach to harmonize real-world data from diverse electronic medical and non-medical platforms to develop a robust and longitudinal dataset. We present pilot data on patients with myocardial infarction (MI) treated with percutaneous coronary intervention (PCI) between 2012 and 2014. The initial data set had 53,395 patients. Of these, 35,203 had CAD confirmed on coronary angiography, of whom 21,521 had PCI. Eventually, limiting to 2012-2014, 3,819 patients had MI with PCI, while 5,989 had MI. Compared with the quality improvement registry, Singapore Cardiac Data Bank, which had 189 fields for analysis, the SingCLOUD platform generated an additional 313 additional data fields, and was able to identify an additional 250 heart failure events, 664 major adverse cardiovascular events at 2 years, and low-density lipoprotein levels to 1 year for 3,747 patients. Conclusions: By integrating multiple incongruent data sources, SINGCLOUD enables in-depth analysis of real-world cardiovascular "big data".

The association of diabetes mellitus (DM) with cardiac resynchronization therapy (CRT) response and cardiovascular outcomes in Asian patients with heart failure (HF) is unclear. This study aims to investigate the effects of DM on CRT response and cardiovascular outcomes in Asian HF patients. Consecutive Asian HF patients receiving CRT were enrolled in the Prospective Evaluation of Asian with CRT for Heart Failure (PEACH) study from 2011 to 2017. CRT response and super-response were defined as decrease in end-systolic volume index ≥15% and ≥30%, respectively. Primary endpoint was time to composite of HF-hospitalization and all-cause mortality. Among 161 patients followed for 3.3 ± 1.5 years (age 66.7 ± 11.2 years, 22% females, mean QRS duration 154.3 ± 22.4 ms, 83% left bundle branch block), 84 (52%) were CRT responders and 57 (35%) were super-responders. Of 82 (51%) patients with DM (100% type 2, mean HbA1c 7.3 ± 1.9%), 35 (43%) were responders. DM attenuated reverse remodeling (CRT response: AOR 0.44, 95% confidence interval [CI] 0.20 to 0.98, p 0.05; super-response: AOR 0.42, 95% CI 0.18 to 0.97, p0.05), and DM increased HF-hospitalization and all-cause mortality (AHR 1.68, 95% CI 1.00 to 2.82, p = 0.05). The extent of CRT-response correlates with higher event-free survival (CRT response: AHR 0.5, 95% CI 0.30 to 0.81, p = 0.005; super-response: AHR 0.27, 95% CI 0.14 to 0.52, p 0.001). In conclusion, the extent of reverse remodeling post-CRT is the strongest predictor of event free survival. However, DM is detrimental to the CRT recipient by attenuating reverse remodeling, inducing end organ dysfunction and is independently associated with worsened clinical outcomes among Asian HF patients.

Increased bleeding risk was found associated with concurrent prescription of rivaroxaban and amiodarone. We previously recommended dose adjustment for rivaroxaban utilizing a physiologically based pharmacokinetic (PBPK) modeling approach. Our subsequent in vitro studies discovered the pivotal involvement of human renal organic anion transporter 3 (hOAT3) in the renal secretion of rivaroxaban and the inhibitory potency of amiodarone. This study aimed to redefine the disease-drug-drug interactions (DDDI) between rivaroxaban and amiodarone and update the potential risks. Prospective simulations were conducted with updated PBPK models of rivaroxaban and amiodarone incorporating hOAT3-related parameters. Simulations to recapitulate previously explored DDDI in renal impairment showed a higher bleeding tendency in all simulation scenarios after integrating hOAT3-mediated clearance into PBPK models. Further sensitivity analysis revealed that both hOAT3 dysfunction and age could affect the extent of DDDI, and age was shown to have a more pivotal role on rivaroxaban in vivo exposure. When amiodarone was prescribed along with our recommended dose reduction of rivaroxaban to 10 mg in moderate renal impaired elderly people, it could result in persistently higher rivaroxaban peak concentrations at a steady state. To better manage the increased bleeding risk among such a vulnerable population, a dose reduction of rivaroxaban to 2.5 mg twice daily resulted in its acceptable in vivo exposure. Close monitoring of bleeding tendency is essential for elderly patients with moderate renal impairment receiving co-prescribed rivaroxaban and amiodarone. Further dose reduction is recommended for rivaroxaban to mitigate this specific DDDI risk.

Background Calcium deposits in the heart have been associated with cardiovascular events, mortality, stroke, and atrial fibrillation (AF). However, there is no accepted standard method for scoring cardiac calcifications. Existing methods have also not been validated for the assessment of patients with embolic stroke of undetermined source (ESUS). The aim of this study was to evaluate the association of various cardiac calcification scores with new-onset AF and stroke recurrence in a cohort of patients with ESUS. Methods In this study, 181 consecutive patients with stroke diagnosed with ESUS were identified and evaluated. They were followed for new-onset AF and ischemic stroke recurrence for a median duration of 2.1 years. Various echocardiographic cardiac calcification scores were assessed on transthoracic echocardiography performed during the evaluation of ESUS and subsequently assessed for their relation to AF detection and recurrent stroke. The echocardiographic calcium scores assessed were the (1) global cardiac calcium score (GCCS), (2) echocardiographic calcium score (eCS), (3) echocardiographic calcification score, (4) echocardiographic composite cardiac calcium score, and (5) total heart calcification score. Only two of these scoring schemes, GCCS and eCS, quantified the cardiac calcium burden. Results Higher calcium scores as measured by GCCS and eCS were found to be significantly associated with subsequent AF detection as well as recurrent ischemic stroke in patients with ESUS. The association with recurrent stroke remained significant even after adjustment for comorbidities and AF. Conclusions Higher cardiac calcification measured using the GCCS and eCS is independently associated with AF detection and recurrent ischemic stroke in patients with ESUS, and these scores can be useful markers for further risk stratification in patients with ESUS.

Background: Several P-wave indices are thought to represent underlying atrial remodeling and have been associated with ischaemic stroke even in the absence of atrial fibrillation (AF). However, the utility of these P-wave indices in predicting outcomes in patients with embolic stroke of undetermined source (ESUS) has not been studied. The aim of this study is to examine these different P-wave indices towards predicting new-onset AF and stroke recurrence in a cohort of patients with ESUS, thereby demonstrating the value of these electrocardiographic markers for stroke risk stratification. Methods: Between October 2014 and October 2017, consecutive patients diagnosed with ESUS were followed for new-onset AF and ischaemic stroke recurrence. The various P-wave indices, namely, the P-terminal force in the precordial lead V1 (PTFV1), P-wave duration, P-wave dispersion, interatrial blocks, and P-wave axis, were assessed on the initial electrocardiogram on presentation and studied for their relation to eventual AF detection and recurrent stroke. Results: 181 ischaemic stroke patients with ESUS were recruited and followed up for a median duration of 2.1 years. An abnormal PTFV1 was associated with occult AF detection but not with recurrent ischaemic strokes. No significant association was observed between the other P-wave indices with either occult AF or stroke recurrence. Conclusion: PTFV1 is associated with AF detection but not recurrent strokes in ESUS patients and can be a useful electrocardiographic marker for further risk stratification in ESUS patients.