Impact of Hemodialysis on Left Ventricular-Arterial Coupling in End-Stage Renal Disease Patients.

INTRODUCTION: As a key determinant of cardiovascular performance, vascular-arterial coupling (VAC) has been reported to be a predictor of clinical outcomes in various clinical scenarios. However, few studies have explored how acute fluid removal during hemodialysis (HD) impacts the interaction between cardiac function and the arterial system. METHODS: We recruited 317 HD patients from an established renal dialysis unit for this cross-sectional study and a total of 285 were included in the final analyses. We measured left ventricle end-systolic elastance (Ees), the effective arterial elastance (Ea), and VAC before and after HD using noninvasive echocardiographic measurements. We also compared echocardiographic and hemodynamic parameters in ventriculo-arterial coupling and ventriculo-arterial uncoupling patients. RESULTS: HD significantly altered partial ventricular and vascular function parameters such as blood pressure, left ventricular end-diastolic volume, stroke volume, left ventricular ejection fraction, and systemic vascular resistance index. Ea increased following HD from 3.5 ± 1.4 to 4.2 ± 1.8 mm Hg/mL (p < 0.0001), Ees increased following HD from 7.9 ± 5.5 to 9.2 ± 6.9 mm Hg/mL (p = 0.04), whereas VAC did not markedly alter as a result of HD. Ventriculo-arterial uncoupling was found to be related to abnormal cardiac structure and worse systolic function. CONCLUSIONS: VAC obtained from echocardiography is likely to be load-independent and useful as a reliable index for stratifying the risk of cardiovascular diseases in HD patients. Further investigations on larger patient cohorts are needed to further validate our findings.

Opportunistic screening for asymptomatic left ventricular dysfunction in type 2 diabetes mellitus.

BACKGROUND: International guidelines recommend natriuretic peptide biomarker-based screening for patients at high heart failure (HF) risk to allow early detection. There have been few reports about the incorporation of screening procedure to existing clinical practice. OBJECTIVE: To implement screening of left ventricular dysfunction in patients with type 2 diabetes mellitus (DM). METHOD: A prospective screening study at the DM complication screening centre was performed. RESULTS: Between 2018 and 2019, 1043 patients (age: 63.7±12.4 years; male: 56.3%) with mean glycated haemoglobin of 7.25%±1.34% were recruited. 81.8% patients had concomitant hypertension, 31.1% had coronary artery disease, 8.0% had previous stroke, 5.5% had peripheral artery disease and 30.7% had chronic kidney disease (CKD) stages 3-5. 43 patients (4.1%) had an elevated N-terminal prohormone of brain natriuretic peptide (NT-proBNP) concentration above the age-specific diagnostic thresholds for HF, and 43 patients (4.1%) had newly detected atrial fibrillation (AF). The prevalence of elevated NT-proBNP increased with age from 0.85% in patients aged <50 years to 7.14% in those aged 70-79 years and worsening kidney function from 0.43% in patients with CKD stage 1 to 42.86% in CKD stage 5. In multivariate logistic regression, male gender (OR: 3.67 (1.47-9.16), p = 0.005*), prior stroke (OR: 3.26 (1.38-7.69), p = 0.007*), CKD (p<0.001*) and newly detected AF (OR: 7.02 (2.65-18.57), p<0.001*) were significantly associated with elevated NT-proBNP. Among patients with elevated NT-proBNP, their mean left ventricular ejection fraction (LVEF) was 51.4%±14.7%, and 45% patients had an LVEF <50%. CONCLUSION: NT-proBNP and ECG screening could be implemented with relative ease to facilitate early detection of cardiovascular complication and improve long-term outcomes.

Body volume is the major determinant of worsening renal function in acutely decompensated heart failure with reduced left ventricular ejection fraction.

AIMS: Little is known about the relative importance of body volume and haemodynamic parameters in the development of worsening of renal function in acutely decompensated heart failure (ADHF). To study the relationship between haemodynamic parameters, body water content and worsening of renal function in patients with heart failure with reduced ejection fraction (HFrEF) hospitalised for ADHF. METHODS AND RESULTS: This prospective observational study involved 51 consecutive patients with HFrEF (age: 73±14 years, male: 60%, left ventricular ejection fraction: 33.3%±9.9%) hospitalised for ADHF. Echocardiographic-determined haemodynamic parameters and body volume determined using a bioelectric impedance analyser were serially obtained. All patients received intravenous furosemide 160 mg/day for 3 days. There was a mean weight loss of 3.95±2.82 kg (p<0.01), and brain natriuretic peptide (BNP) reduced from 1380±901 pg/mL to 797±738 pg/mL (p<0.01). Nonetheless serum creatinine (SCr) increased from 134±46 µmol/L to 151±53 µmol/L (p<0.01), and 35% of patients developed worsening of renal function. The change in SCr was positively correlated with age (r=0.34, p=0.017); and negatively with the ratio of extracellular water to total body water, a parameter of body volume status (r=-0.58, p<0.001); E:E' ratio (r=-0.36, p=0.01); right ventricular systolic pressure (r=-0.40, p=0.009); and BNP (r=-0.40, p=0.004). Counterintuitively, no correlation was observed between SCr and cardiac output, or total peripheral vascular resistance. Regression analysis revealed that normal body volume and lower BNP independently predicted worsening of renal function. CONCLUSIONS: Normal body volume and lower serum BNP on admission were associated with worsening of renal function in patients with HFrEF hospitalised for ADHF.

Antithrombotic therapy and the risk of new-onset dementia in elderly patients with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is associated with an increased risk of dementia. Little is known about the relationship of antithrombotic therapy and the risk of dementia in patients with AF without clinical stroke. METHOD: This was an observational study based on a hospital AF registry. Patients aged 65-85 years at the time of AF diagnosis were identified via the computerised database of the clinical management system. Patients with prior stroke or known cognitive dysfunction were excluded. The primary outcome was newly diagnosed dementia during the follow-up period. RESULTS: 3284 patients (mean age 76.4±5.3 years, 51.6% male) were included for analysis. The mean CHA2DS2-VASc score was 3.94±1.44. 18.5% patients were prescribed warfarin, 39.8% were prescribed aspirin and 41.7% were prescribed no antithrombotic therapy. After a mean follow-up of 3.6 years, 71 patients (2.2%) developed dementia, giving rise to an incidence of 0.61%/year. The incidence of dementia were 1.04%/year, 0.69%/year and 0.14%/year for patients on no therapy, aspirin and warfarin, respectively. Both univariate and multivariate analyses showed that age ≥75 years, female gender and high CHA2DS2-VASc score were associated with significantly higher risk of dementia; warfarin use was associated with significantly lower risk of dementia (HR: 0.14%, 95% CI 0.05 to 0.36, p<0.001). Patients on warfarin with time in therapeutic range (TTR) ≥65% had a non-significant trend towards a lower risk of dementia compared with those with TTR <65%. CONCLUSION: In elderly AF patients, warfarin therapy was associated with a significantly lower risk of new-onset dementia compared those with no therapy or aspirin.

The impact of cigarette smoking in predicting stroke using CHADS2 and CHA2DS2-VASc schemas.

OBJECTIVE: To determine the impact of smoking status in the prediction of stroke using CHADS2 and CHA2DS2-VASc schemes. METHODS: Five hundred twenty-eight consecutive patients with arrhythmic symptoms and without any documented arrhythmia from Queen Mary Hospital, Hong Kong, were followed up to determine the incidence of ischemic stroke, new-onset atrial fibrillation (AF), or all-cause mortality. Smoking status was classified into nonsmokers and smokers. The pairwise comparisons of C-statistics for outcomes were performed. RESULTS: During a median follow-up period of 6.2 years, 65 (12.3%) individuals developed ischemic stroke. Smokers experienced higher annual incidence of stroke, a new-onset AF, and all-cause death compare to nonsmokers, with corresponding hazard ratio (HR) of stroke, AF, and all-cause death being 2.51 (95% confidence intervals, CI 1.36als, CIse death bein 1.15a3.24), and 1.95 (95% CI 1.161.95 (95% CIath being 2.51 (95% confidence corr2 and CHA2DS2-VASc for stroke were 0.60 (95% CI 0.51 for stp = 0.09) and 0.59 (95% CI 0.50 (95%, p = 0.15) respectively, whereas the C-statistics of CHADS2 and CHA2DS2-VASc were 0.66 (95% CI 0.61 were 0p = 0.005), 0.75 (95% CI 0.7 CI 0.7p < 0.0001), respectively among nonsmokers. After incorporating smoking, both the CHADS2-smoking and CHA2DS2-VASc-smoking achieved better C-statistics for new-onset ischemic stroke prediction superior to baseline score systems in male groups. CONCLUSION: Cigarette smoking status has impact on stroke stratification using CHADS2 and CHA2DS2-VASc scheme. The discrimination of the CHADS2 and CHA2DS2-VASc scheme for stroke can be significantly improved if smoking status is additionally considered.

Prevalence of and associations with reduced exercise capacity in peritoneal dialysis patients.

BACKGROUND: Exercise capacity is reduced in patients with end-stage renal disease on maintenance home peritoneal dialysis therapy, although the potential mechanisms and clinical implications remain unclear. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: 95 ambulatory prevalent and incident peritoneal dialysis patients in a well-established renal dialysis center (mean age, 58.26 ± 12.6 [SD] years; 63% men; mean duration of peritoneal dialysis therapy, 3.2 ± 4.1 years). PREDICTOR: Estimated volume status using spectral bioelectrical impedance, echocardiography-derived hemodynamic parameters. OUTCOME: Exercise capacity measured as peak oxygen consumption using symptom-limiting treadmill exercise testing. RESULTS: Exercise capacity was reduced in 96% of patients and severely reduced in 65%. Extracellular to intracellular fluid volume ratio showed the strongest correlation with reduced exercise capacity (R = -0.63; P < 0.001) and was superior to age, pulmonary capillary wedge pressure (E:E' ratio), lean tissue mass index, and hemoglobin and albumin levels in predicting exercise intolerance. LIMITATIONS: Relatively small sample size and echocardiogram that was performed only at rest. CONCLUSIONS: There was a strong relationship between body extracellular to intracellular fluid volume ratio and exercise capacity in peritoneal dialysis patients. These findings provide new evidence for a connection between fluid distribution, muscle mass, and exercise capacity. Therapeutic strategies targeting fluid status and muscle mass may improve the exercise capacity of patients on peritoneal dialysis therapy.

Frequent premature atrial complexes predict new occurrence of atrial fibrillation and adverse cardiovascular events.

AIMS: To investigate the relation between baseline frequency of premature atrial complexes (PACs) and new atrial fibrillation (AF) and adverse cardiovascular events. METHOD AND RESULTS: Four hundred and twenty-eight patients without AF or structural heart disease undergoing 24 h electrocardiography monitoring for palpitations, dizziness, or syncope were recruited. One hundred and seven patients with number of PACs at the top quartile (i.e. > 100PACs/day) were defined to have frequent PACs. After 6.1-year follow-up, 31 patients (29%) with frequent PACs developed AF compared with 29 patients (9%) with PACs ≤ 100/day (P< 0.01). Cox regression analysis revealed that frequent PACs [hazard ratio (HR): 3.22 (95% confidence interval (CI): 1.9-5.5; P< 0.001)], age >75 years (HR: 2.3; 95% CI: 1.3-3.9; P= 0.004), and coronary artery disease (HR: 2.5; 95% CI: 1.4-4.4; P= 0.002) were independent predictors for new AF. Concerning the composite endpoint (ischaemic stroke, heart failure, and death), patients with frequent PACs were more at risk than those without (34.5 vs. 19.3%) (HR: 1.95; 95% CI: 1.37-3.50; P= 0.001). Cox regression analysis showed that age >75 years (HR: 2.2; 95% CI: 1.47-3.41; P< 0.001), coronary artery disease (HR: 2.2, 95% CI: 1.42-3.44, P< 0.001), and frequent PACs (HR: 1.6; 95% CI: 1.04-2.44; P= 0.03) were independent predictors for the secondary composite endpoint. CONCLUSION: Frequent PACs predict new AF and adverse cardiovascular events.

Daily ambulatory remote monitoring system for drug escalation in chronic heart failure with reduced ejection fraction: pilot phase of DAVID-HF study.

Aims: Underutilization of guideline-directed heart failure with reduced ejection fraction (HFrEF) medications contributes to poor outcomes. Methods and results: A pilot study to evaluate the safety and efficacy of a home-based remote monitoring system for HFrEF management was performed. The system included wearable armband monitors paired with the smartphone application. An HFrEF medication titration algorithm was used to adjust medication daily. The primary endpoint was HFrEF medication utilization at 120 days. Twenty patients (60.5 ± 8.2 years, men: 85%) with HFrEF were recruited. All received angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI) at recruitment; 45% received ≥50% maximal targeted dose (MTD) with % MTD of 44.4 ± 31.7%. At baseline, 90 and 70% received beta-adrenergic blocker and mineralocorticoid receptor antagonist (MRA), 35% received ≥50% MTD beta-adrenergic blocker with % MTD of 34.1 ± 29.6%, and 25% received ≥50% MTD MRA with % MTD of 25.0 ± 19.9%. At 120 days, 70% received ≥50% MTD ACEI/ARB/ARNI (P = 0.110) with % MTD increased to 64.4 ± 33.5% (P = 0.060). The proportion receiving ≥50% MTD ARNI increased from 15 to 55% (P = 0.089) with % MTD ARNI increased from 20.6 ± 30.9 to 53.1 ± 39.5% (P = 0.006*). More patients received ≥50% MTD MRA (65 vs. 25%, P = 0.011*) with % MTD MRA increased from 25.0 ± 19.9 to 46.2 ± 28.8% (P = 0.009*). Ninety-five per cent of patients had reduced NT-proBNP with the percentage reduction of 26.7 ± 19.7%. Conclusion: Heart failure with reduced ejection fraction medication escalation with remote monitoring appeared feasible.

Protocol for Home-Based Solution for Remote Atrial Fibrillation Screening to Prevent Recurrence Stroke (HUA-TUO AF Trial): a randomised controlled trial.

INTRODUCTION: Current international guidelines recommend ECG monitoring after an ischaemic stroke to detect atrial fibrillation (AF) in order to prevent stroke recurrence. However, optimal strategies to detect AF and the downstream management to prevent stroke recurrence remain to be established. The objective of the study was to explore the use of long-term home-based ECG monitoring for AF detection and stroke prevention in patients with a history of stroke. METHODS AND ANALYSIS: This prospective, randomised, open-label trial with blinded endpoint adjudication aimed to evaluate the efficacy of long-term home-based ECG monitoring for AF detection and stroke prevention in a 24-month period. Patients aged >18 years with a history of ischaemic stroke will be stratified according to the time from the index ischaemic stroke: <1, 1-3 and >3 years and then randomised in 1:1 to (1) home-based AF screening and (2) control. The home-based AF screening system comprises (1) a handheld single-lead ECG recorder (Comfit Healthcare Devices, Hong Kong SAR, China) and (2) a patient-facing smartphone application specially designed for the study. Patients randomised to the home-based AF group will record a 30 s single-lead ECG using a specially designed handheld ECG device every morning or when symptomatic. All remotely obtained data will be automatically transmitted in real-time through the study smartphone application to a secured cloud hosting and analysed using an artificial intelligence-based diagnostic system. When a diagnosis of AF is made with the system, the patients will be called back for a formal cardiology consultation within 1 week. The primary endpoint is the time to first detection of AF at 24 months of follow-up. Secondary endpoints include recurrent stroke or transient ischaemic attack, initiation of long-term anticoagulation therapy, hospitalisation for heart failure, cardiovascular death and all-cause death. ETHICS AND DISSEMINATION: The study protocol has been approved by the institutional review board of The University of Hong Kong, and Hong Kong West Cluster, Hospital Authority, Hong Kong SAR, China. Results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04523649.

Risk of venous thromboembolism in Chinese pregnant women: Hong Kong venous thromboembolism study.

BACKGROUND: Previous Caucasian studies have described venous thromboembolism in pregnancy; however, little is known about its incidence during pregnancy and early postpartum period in the Chinese population. We investigated the risk of venous thromboembolism in a "real-world" cohort of pregnant Chinese women with no prior history of venous thromboembolism. METHODS: In this observational study, 15,325 pregnancies were identified in 14,162 Chinese women at Queen Mary Hospital, Hong Kong between January 2004 and September 2016. Demographic data, obstetric information, and laboratory and imaging data were retrieved and reviewed. RESULTS: The mean age at pregnancy was 32.4±5.3 years, and the median age was 33 years (interquartile range, 29-36 yr). Pre-existing or newly diagnosed diabetes mellitus was present in 627 women (4.1%); 359 (0.7%) women had pre-existing or newly detected hypertension. There was a small number of women with pre-existing heart disease and/or rheumatic conditions. Most deliveries (86.0%) were normal vaginal; the remaining were Cesarean section 2,146 (14.0%). The incidence of venous thromboembolism was 0.4 per 1,000 pregnancies, of which 83.3% were deep vein thrombosis and 16.7% were pulmonary embolism. In contrast to previous studies, 66.7% of venous thrombosis occurred in the first trimester. CONCLUSION: Chinese women had a substantially lower risk of venous thromboembolism during pregnancy and the postpartum period compared to that of Caucasians. The occurrence of pregnancy-related venous thromboembolism was largely confined to the early pregnancy period, probably related to the adoption of thromboprophylaxis, a lower rate of Cesarean section, and early mobilization.

The CHADS2 and CHA 2DS 2-VASc scores predict new occurrence of atrial fibrillation and ischemic stroke.

BACKGROUND: Early identification of individuals who are at risk of developing atrial fibrillation (AF) and ischemic stroke may enable a closer surveillance and thus prompt initiation of oral anticoagulation for stroke prevention. OBJECTIVE: This study sought to investigate whether congestive heart failure, hypertension, age ≥ 75 years, diabetes, previous stroke (CHADS2) and CHA2DS2-vascular disease, age 65-74 years, sex category (CHA2DS2-VASc) scores can predict new-onset AF and/or ischemic stroke in patients presenting with arrhythmic symptoms. METHODS AND RESULTS: We prospectively followed up 528 patients (68.5 ± 10.6 years, male 46.2 %) presented for assessment of arrhythmic symptoms but without any documented arrhythmia, including AF for development of new-onset AF and/or ischemic stroke. Their mean CHADS2 and CHA2DS2-VASc scores on presentation were 1.3 ± 1.3 and 2.3 ± 1.5, respectively. After 6.1 years, 89 patients (16.8 %, 2.77 per 100 patient-years) had documented AF, and 65 patients (12.3 %, 2.0 per 100 patient-years) suffered stroke. Both the CHADS2 (C statistic 0.63, 95 % confidence interval (CI) 0.58-0.67, P < 0.0001, optimal cutoff at 1) and CHA2DS2-VASc (C statistic 0.63, 95 % CI 0.59-0.67, P < 0.0001, optimal cutoff at 2) scores provided similar prediction for the new-onset AF. Similarly, CHADS2 (C statistic 0.69, 95 % CI 0.65-0.73, P < 0.0001, optimal cutoff at 2) and CHA2DS2-VASc (C statistic 0.69, 95 % CI 0.65-0.73, P < 0.0001, optimal cutoff at 2) have compatible efficacy for stroke prediction in this Chinese population. CONCLUSION: The CHADS2 and CHA2DS2-VASc scores can be used in patients who presented with arrhythmic symptoms to identify those who are at risk with developing new-onset clinical AF and ischemic stroke for close clinical surveillance and early intervention.

Use of aspirin in Chinese after recovery from primary intracranial haemorrhage.

Intracranial haemorrhage (ICH) accounts for ~35% of all strokes in Chinese. Anti-platelet agent is often avoided after an index event due to the possibility of recurrent ICH. This single-centered observational study included 440 consecutive Chinese patients with a first spontaneous ICH surviving the first month performed during 1996-2010. The subjects were identified, and their clinical characteristics, anti-platelet therapy after ICH, and outcomes including recurrent ICH, ischaemic stroke, and acute coronary syndrome were checked from hospital records. Of these 440 patients, 56 patients (12.7%) were prescribed aspirin (312 patient-aspirin years). After a follow-up of 62.2 ± 1.8 months, 47 patients had recurrent ICH (10.7%, 20.6 per 1,000 patient years). Patients prescribed aspirin did not have a higher risk of recurrent ICH compared with those not prescribed aspirin (22.7 per 1,000 patient-aspirin years vs. 22.4 per 1,000 patient years, p=0.70). Multivariate analysis identified age > 60 years (hazard ratio [HR]: 2.0, 95% confidence interval [CI]: 1.07-3.85, p=0.03) and hypertension (HR: 2.0, 95% CI: 1.06-3.75, p=0.03) as independent predictors for recurrent ICH. In a subgroup analysis including 127 patients with standard indications for aspirin of whom 56 were prescribed aspirin, the incidence of combined vascular events including recurrent ICH, ischaemic stroke, and acute coronary syndrome was statistically lower in patients prescribed aspirin than those not prescribed aspirin (52.4 per 1,000 patient-aspirin years, vs. 112.8 per 1,000 patient-years, p=0.04). In conclusion, we observed in a cohort of Chinese post-ICH patients that aspirin use was not associated with an increased risk for a recurrent ICH.