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Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Sanmin project, Shenzhen, China Background There is inconclusive evidence regarding the impact of statins on the risk of atrial fibrillation (AF) related outcomes. The current study investigated whether statin use would improve outcomes among patients with non-valvular AF. Purpose To assess the association between statin use and AF-related outcomes among patients with AF. Methods Patients newly diagnosed with AF (n = 51,472) between 2010-2018 were divided into statin users (n =11,866) and statin nonusers (n =39,606), according to whether they received statin therapy after their first diagnosis of AF. The primary outcomes included ischaemic stroke (IS) and systemic embolism (SE), haemorrhagic stroke (HS), and transient ischaemic attack (TIA). An inverse probability of treatment weighting was used to balance baseline covariates between the two groups. The Fine and Grey competing risks model was applied, with death defined as the competing event. Results The median age of the cohort was 74.9 years, and 47.7% were female. During the median follow-up of 5.1 years, previous statin use was significantly associated with a lower risk of IS/SE compared with statin nonusers (subdistribution hazard ratio [SHR] = 0.83, 95%CI: 0.78-0.89). Similar patterns were found in the association between previous statin use and HS (SHR = 0.93, 95%CI: 0.89-0.98) and TIA (SHR = 0.85, 95%CI: 0.80-0.90, P Conclusion Statin use was associated with a lower risk of incident IS/SE, HS and TIA in a duration-dependent manner among AF patients.

Funding Acknowledgements Type of funding sources: None. Background Hyperkalemia is a common complication and increases the risk of cardiac arrhythmias and mortality in patients with type 2 diabetes (T2DM), especially in those with diabetic nephropathy. We investigated the risk of hyperkalemia in patients initiated on SGLT2 inhibitors versus DPP-4 inhibitors among patients with T2DM. Methods This study included patients with T2DM who initiated on SGLT2 inhibitors or DPP-4 inhibitors between January 01, 2015 and December 31, 2019 from a territory-wide clinical registry in Hong Kong (Clinical Data Analysis and Reporting System [CDARS]). A multivariable cox proportional hazards analysis, adjusting for key confounders, was used to compare the risk of central laboratory-determined hyperkalemia (serum potassium ≥6.0mmol/L) and hypokalemia (serum potassium Results 10193 new users of SGLT2 inhibitors were matched to 17305 new users of DPP-4 inhibitors. During the 2-year follow-up, there were 104 hyperkalemia events (incident rate [IR] = 5.17 per 1000 person-years) among SGLT2 inhibitors and 306 events (IR = 9.09 per 1000 person-years) among DPP-4 inhibitors, of which SGLT2 inhibitors were associated with a lower risk of incident hyperkalemia (Adjusted HR: 0.66 [95%CI 0.53-0.83], p Conclusion SGLT2 inhibitors reduced incident hyperkalemia, but without increasing incident hypokalemia compared to DPP-4 inhibitors.

Background The 2020 ESC guideline for atrial fibrillation (AF) recommends universal quality indicators to identify areas for improvement in clinical practice. It also recommends using clinical registries to monitor clinical practice and identify areas for improvement. We have analysed two large comprehensive prospective clinical registries of patients with AF, the EURObservational Research Programme (EORP) and the Asia Pacific Heart Rhythm Society (APHRS), to compare the achievement of the ESC quality indicators in two major world populations. Methods The EORP and APHRS registries used the same electronic case report forms to collect data. T-test and Chi-squared test were used to compare registries. Logistic regression was used to identify pharmacological rate control therapy predictors in permanent AF. The model was adjusted for age, oral anticoagulation (OAC), EHRA and CHA2DS2-VASc scores, heart rate on the latest ECG and the region of recruitment (Europe or Asia) (STATA Corp, version 13). Results All 11096 EORP patients (59.3% males, age 69±11 years) and 5460 APHRS patients (66.3% males, age 68±12 years) had CHA2DS2-VASc and HAS-BLED scores documented at enrolment. The EORP register included a higher proportion of patients with CHA2DS2VASc ≥2 (81% vs 70%, p In patients with permanent AF, heart rate (82±20 vs 78±20, p APHRS vs EORP patients with non-permanent AF were less symptomatic (EHRA score I in 56% vs 38%) with less frequent use of antiarrhythmics (25% vs 37%), rhythm-management interventions (32% vs 46%), but higher use of catheter ablation (p Conclusion There are significant regional variations in achievement of the ESC quality indicator for AF. The variations may be due to differences in healthcare systems, but they may also reflect the population characteristics. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Since the start of EORP, the following companies have supported theprogramme: Abbott Vascular Int. (2011-2014), Amgen Cardiovascular(2009-2018), AstraZeneca (2014-2017), Bayer AG (2009-2018),Boehringer Ingelheim (2009-2019), Boston Scientific (2009-2012), TheBristol Myers Squibb and Pfizer Alliance (2011-2016), The Alliance DaiichiSankyo Europe GmbH and Eli Lilly and Company (2011-2017), Edwards(2016-2019), Gedeon Richter Plc. (2014-2017), Menarini Int. Op. (2009-2012), MSD-Merck & Co. (2011-2014), Novartis Pharma AG (2014-2017), ResMed (2014-2016), Sanofi (2009-2011), and SERVIER (2009-2018).The Atrial Fibrillation NETwork (AFNET), conducting the registryin Germany, received support from The Bristol Myers Squibb/PfizerAlliance (2014-2018) and the German Centre for CardiovascularResearch (DZHK).

Objective Severe aortic stenosis (AS) is the primary valvular heart disease, treatable only by aortic valve replacement (AVR). The prognostic value of pre-operative left atrial (LA) function on post-AVR clinical outcomes is uncertain. The study aims to evaluate the prognostic value of pre-operative peak atrial longitudinal strain (PALS) as a surrogate of LA function on post AVR all-cause mortality and heart failure hospitalisation. Methods Patients aged 18 years old or above with severe AS were recruited and assessed using speckle-tracking echocardiography pre-operatively. Severe AS was defined according to 2014 AHA/ACC Guideline for the Management of Patients with Valvular Heart Disease. PALS was measured. Based on the median value of PALS, patients were stratified into PALS 15.94%. Patients with underlying pre-operative atrial fibrillation, other moderate to severe valvular heart diseases and cancers were excluded. Patients were followed up until death, heart failure hospitalisation or end of the study. The primary outcome is a composite endpoint of all-cause mortality and heart failure hospitalisation. The association of PALS with the composite endpoint was evaluated by Cox Proportional Hazards analysis. Results A total of 128 patients (mean age 65.32±9.42 years, 56.3% male) were prospectively analyzed. Patients were followed up for a mean period of 3.9±2.4 years. A total of 65 of 128 patients (50.8%) belonged to PALS Conclusion The study demonstrated a lower pre-operative PALS is associated with all-cause mortality and heart failure admission in patients with severe AS undergoing AVR. Evaluation of LA function by assessing speckle tracking derived PALS may aid in prognostication for patients undergoing AVR. Funding Acknowledgement Type of funding sources: None.

Funding Acknowledgements Type of funding sources: None. Background Dementia, in the setting of heart failure (HF), portends poorer outcomes and poses great challenges in its clinical management. Purpose We investigated the incidence, types, clinical correlates, and the prognostic impact of dementia in a population-based cohort of patients with HF. Further, we examined the interactions of age and sex, and education status with dementia incidence. Methods The previously validated Hong Kong Clinical Data Analysis Reporting System (CDARS), a territory-wide database was interrogated to identify patients with HF (N= 202,121) from 1995 to 2018. Associations of clinical correlates with incident dementia and its risk with all-cause mortality were assessed using competing risk/multivariable Cox regression models where appropriate. Results Among a total cohort aged ≥18 years with HF (mean age: 75.3 ± 13.0 years, 51.3% women), new-onset dementia occurred in 22,145 (11.0%) over a median follow-up of 5.5 years. Alzheimer’s disease occurred in 27.0%; vascular dementia (18.1%) and unspecified dementia (in 55.1%). Age-standardized rate of dementia incidence in women was 1297 (95%CI, 1276-1318) (vs. 744, 95%CI, 723-765) per 10000 population in men. Other independent predictors of dementia include: Increasing age (HR 1.08), Female sex (HR 1.19), Nil/< primary (vs tertiary) education (HR 1.29), Parkinson’s disease (HR 1.73), head injury (HR 1.37), peripheral vascular disease (HR 1.31), stroke (HR 1.29), depression (HR 1.18), alcohol intake (HR1.17), anaemia (HR 1.14), hypertension (HR 1.08), among other common comorbidities in HF (Figure 1A). Notably, a significant interaction (p Conclusions Female sex, lower socioeconomic status, increasing age and common comorbidities were associated with higher hazards of incident dementia. Abstract Figure 1A and Figure 1B

Funding Acknowledgements Type of funding sources: None. Background Diabetes, chronic kidney disease (CKD) and heart failure (HF) are fast-growing causes of morbidity and mortality worldwide. Diabetes is an optimal model to study the inter-play of cardiovascular disease and renal disease. Purpose To investigate the association of CKD with HF and its prognosis in a large, population-based cohort of diabetes, in which incident CKD and HF events were ascertained longitudinally. Methods A population-based cohort of patients aged ≥18 years with diabetes, but without CKD, HF or acute kidney injury at baseline was identified from the previously validated territory-wide Clinical Data Analysis Reporting System between 2000 and 2015. Patients were followed up through December 31,2020 for incident CKD and/or HF or all-cause mortality. Multi-state modelling was used to examine the association of the subgroups (with/without CKD or HF). Results Among 294,413 patients (mean age: 65 ± 14 years; 49.5% women), new-onset CKD occurred in 51,583, in whom one-fifth (21.3%) had HF. In contrast, among 28,335 patients with new-onset HF, nearly two-fifth (38.7%) had CKD (Figure 1A). Median duration from baseline to incident CKD was shorter than incident HF [8.27 (4.69-11.97) years vs. 8.76 (5.28-12.37) years, p Presence of CKD was associated with incident HF (odds ratios [OR] 1.27 [95%CI 1.21-1.33]), and HF with incident CKD (OR 1.26 [95%CI 1.18-1.33]). The presence of both CKD and HF (regardless of which comes first) portends higher risk (6 to 8-fold hazards) of all-cause mortality than neither condition (Figure 1B). Conclusions Incident HF occurs in one-fifth of patients with new-onset CKD, and CKD occurs in about 40% with new-onset HF. CKD seems to precede HF. More research on the inter-play of these dual conditions is warranted in view of the high mortality risk. Abstract Figure.

Funding Acknowledgements Type of funding sources: None. Objective Severe aortic stenosis (AS) is the most common primary valvular heart disease, treatable only by aortic valve replacement (AVR). Current literatures have shown that severe AS may precede atrial dysfunction which predicts adverse outcomes. However, predictive value of pre-operative left atrial (LA) function on post-AVR clinical outcomes is uncertain. The study aims to evaluate the prognostic value of pre-operative LA strain on post AVR all-cause mortality and heart failure. Methods Patients aged 18 years old or above with severe AS were recruited and assessed using speckle-tracking echocardiography pre-operatively. Severe AS was defined according to 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease. Peak Atrial Longitudinal Strain (PALS) was measured as a surrogate of LA function. Patients with underlying pre-operative atrial fibrillation and other severe valvular heart diseases were excluded. High PALS was defined as PALS higher than 15.94%. Patients were followed up until death or end of the study. The primary endpoint is a composite endpoint of all-cause mortality and heart failure during hospitalisation. The association of LA function with composite endpoint of all-cause mortality and heart failure was evaluated by Cox Proportional Hazards analysis. Results A total of 128 patients (mean age 65.3.9 ± 9.4 years, 56.3% male) were analysed. Patients were followed up for a mean period of 3.9 ± 2.4years. A total of 65 of 128 patients (50.8%) belonged to low PALS group. During the study period, 23 patients developed events on the composite endpoint. Among those with composite endpoint, low PALS group accounted for 18 (78.3%) patients and high PALS group accounted for 5 (21.7%) patients. Higher PALS was independently associated with lower risk of composite endpoint of all-cause mortality and heart failure (HR, 0.33; 95% CI 0.117-0.916, p = 0.03) after adjustment for EuroSCORE II. Conclusion Higher PALS, a surrogate of LA function, is associated with a lower risk of composite endpoints of mortality and heart failure in patients with severe AS undergoing AVR, independent of EuroSCORE II. Evaluation of LA function by assessing speckle tracking derived PALS may aid in prognostication for patients undergoing AVR.

Background There are considerable sex differences in patients with myocardial infarction (MI). However, the recent temporal trends in characteristics and outcomes in women vs. men, particularly in an Asian population, remain poorly understood. Purpose We aim to evaluate the sex differences in characteristics and outcomes, and how have these differences evolved over the past 2 decades in patients with MI. Methods From a well-validated territory-wide database in Hong Kong, we included patients with incident acute MI from 1999/01/01 to 2018/12/31. Outcomes of interest include, at 30 days, all-cause death, new-onset heart failure (HF), and ischaemic stroke. Trends in sex differences in baseline characteristics were evaluated using linear and Poisson regression, while differences in outcomes were evaluated using Cox proportional hazard model, adjusted with demographics, comorbidities, and baseline medications. A Fine-Gray model was used to evaluate HF and ischaemic stroke to account for competing risk, with all-cause death defined as competing event. Results A total of 130,218 patients (age 73.6±13.9 years, 40.0% female) were included. Women were older (79.5±11.7 vs. 69.6±13.8 years, P Although the crude 30-day mortality rate was higher in women (32.6% vs 23.9%), after adjustment for confounders, they had a lower risk of death (hazard ratio [HR] 0.97, 95% CI [0.96 to 0.99], P=0.003). There was no significant difference in the decreasing trend in 30-day mortality between both sexes (interaction P=0.787) (Figure 1). Women had a higher risk of developing HF (HR 1.04 [1.01 to 1.08], P=0.012) and ischemic stroke (HR 1.36 [1.24 to 1.48], P Among patients aged ≤55 (N=15,324), women (N=2,161, 14.1%) had higher risks of all-cause death (HR 1.61 [1.40 to 1.85], P Conclusions Women MI patients were older and more comorbid compared to men, which contributed to the higher risk of death, HF, and ischemic stroke among women. Among young MI patients, the increased risk for adverse outcomes among women was particularly pronounced, though the sex differences in mortality reduced over time. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): The Shenzhen Key Medical DisciplineThe Sanming Project of HKU-SZH Cardiology

Introduction Despite class IA guideline recommendations, the use of fractional flow reserve (FFR) in guiding percutaneous coronary intervention (PCI) in stable coronary artery disease (CAD) patients remains low due to limitations including the need of guidewire placement and hyperaemic stimulus. A novel non-invasive index, computational pressure-flow dynamics derived FFR (caFFR), was developed for measuring functional myocardial ischemia and overcoming the limitations of FFR. However, the clinical relevance of caFFR remains to be investigated. In the present study, we aim at evaluating the prognostic value of caFFR among stable CAD patients. Methods We retrospectively included patients with stable CAD who underwent coronary angiography during 2014–2016 at our center. Based on the caFFR value, patients were considered to be ischemic (caFFR ≤0.8) and non-ischemic (caFFR >0.8). Further, we recombined the patients to form the adherence cohort, where patients were defined as adherent-to-caFFR if they were ischemic with PCI or non-ischemic without PCI, and nonadherent-to-caFFR if they were ischemic without PCI or non-ischemic with PCI. The primary endpoint was major adverse cardiac events (MACE), defined as a composite of all-cause mortality, non-fatal myocardial infarction, and any revascularization. Inverse probability of treatment weighting was used to account for treatment selection bias (PCI vs without PCI, or adherent vs non-adherent), and Cox proportional hazard model was used to evaluate the association with MACE. Results A total of 1322 patients, 782 patients in the ischemic cohort and 540 patients in the non-ischemic cohort respectively, were included in our analysis. PCI was associated with a lower risk of MACE in the ischemic cohort (hazard ratio [HR] 0.52; 95% confidence interval [CI], 0.34–0.80; P=0.002), but was not associated with MACE in the non-ischemic cohort. In the adherence cohort, adherent-to-caFFR group (n=803) had a lower risk of MACE compared with nonadherent-to-caFFR group (n=566) (HR, 0.61; 95% CI, 0.44–0.85; P=0.003). Conclusion Our study is the first to demonstrate the prognostic value of caFFR, a non-wire based assessment of myocardial ischemia, in patients with stable CAD undergoing PCI. These findings support the use of caFFR that bears the potential of a wider adoption compared with wire-based FFR through a reduction in procedure time, risk and costs. Funding Acknowledgement Type of funding sources: None. Weighted Kaplan-Meier curvesWeighted Cox proportional hazards model

Background Diabetic kidney disease is a major diabetic complication which contributes to the end-stage renal disease and renal deaths in diabetic patients. The aim of our study was to investigate the role of pulmonary hypertension (PHT) in the development of adverse renal outcomes in patients with type 2 diabetes (T2DM). Methods A total of 1479 diabetic patients (mean age 67±13 years; women, 44.7%) were recruited. Pulmonary artery systolic pressure (PASP) was estimated by transthoracic echocardiography at baseline. Adverse renal outcomes were defined as a composite endpoint of a sustained 40% decline in eGFR, end-stage renal disease requiring renal replacement therapy, kidney transplantation or renal deaths. Cox regression hazard model was used to assess the association between PHT and incident adverse renal outcomes. Results Patients were divided into three groups based on their baseline PASP: no PHT (n=1204, 75.1%), mild PHT (321, 20.0%) and significant PHT (78, 4.9%). A total of 474 adverse renal outcomes occurred during a median follow-up of 53 months, Kaplan-Meier survival curve showed that patients with significant PHT had highest risk of adverse renal outcomes. Multivariate cox regression demonstrated both mild PHT (HR=1.66, 95% CI 1.33, 2.06, P Conclusion The presence of PHT was associated with adverse renal outcomes in patients with T2DM. Funding Acknowledgement Type of funding sources: None.

Background Hepatorenal dysfunction and malnutrition are frequent extracardiac consequences of valvular heart disease (VHD) and have emerged as prominent drivers of adverse prognosis in selected valvular interventions. Nonetheless, data in a general VHD population is sparse, and their interaction and changes following valvular surgery remain unexplored. Purpose We aim to characterise the temporal changes, interaction, and prognostic implications of hepatorenal dysfunction and malnutrition before and after valvular surgery. Methods Baseline and temporal changes in hepatorenal dysfunction (assessed by the modified model for end-stage liver disease [MELD-XI] score) and nutritional status (assessed by Controlling Nutritional Status [CONUT] score) were correlated with adverse events (composite of all-cause mortality and hospitalisation for heart failure) using Cox proportional hazards model, adjusted with clinical and echocardiographic covariates, medications, type of valvular procedure, and cardiac surgery risk-stratification models (EuroSCORE II and STS score). Results Our study included 909 patients who underwent valvular surgery. At baseline, 216 (24%) and 554 (61%) had hepatorenal dysfunction (MELD-XI >12.43) and malnutrition (CONUT ≥2), respectively. MELD-XI scores were modestly correlated with CONUT scores (R=0.36, p Over a median follow-up of 4.1 years, 101 (11%) patients died and 119 (13%) were hospitalised for heart failure. There was a stepwise increase in mortality (χ2 89.1, p In patients with MELD-XI and CONUT scores 1 year after surgery (n=707), ΔMELD-XI (follow-up MELD-XI minus baseline MELD-XI score) and ΔCONUT scores were significantly associated with adverse events (HR 1.08, 95% CI 1.03–1.14, p=0.001 for ΔMELD-XI; HR 1.18, 95% CI 1.02–1.35, p=0.02 for ΔCONUT). Patients remaining with hepatorenal dysfunction and malnutrition experienced worse survival (log-rank χ2 65.2, p Conclusions In patients undergoing valvular surgery, hepatorenal function and nutritional status at baseline, and their temporal changes, are strongly linked to clinical outcomes. These results highlight the role of hepatorenal and nutritional assessment for risk-stratification in valvular surgery. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

Background The burden of myocardial infarction (MI) with its assorted comorbid complications is increasing parallel to rising life expectancy. Careful characterisation of patient characteristics and identification of short- and long-term complications is critical to their management. Nonetheless, data on the evolving profiles of patient features and outcomes, particularly in an Asian population, remain sparse. Purpose We aim to describe the evolving characteristics and outcomes of MI patients in Hong Kong in the past 2 decades. Methods From a well-validated territory-wide database in Hong Kong, we included patients with incident acute MI from 1999/01/01 to 2018/12/31. The primary outcome was 30-day all-cause death, while secondary outcomes include haemorrhagic stroke, and pneumonia, at both 30 days and 5 years. Temporal trends in baseline characteristics were evaluated using Poisson regression, while trends in outcomes were evaluated using Cox proportional hazard model, adjusted with demographics, comorbidities, and baseline medications. Results A total of 130,218 patients (age 73.6±13.9 years, 40.0% female) were included. Over time, while there was no change in the proportion of females (P=0.196), the increase in mean age (APC 0.23% [0.21 to 0.24], P The adjusted all-cause 30-day mortality rate decreased increased significantly (APC 0.3% [0.1 to 0.5], P=0.005). The increasing trend was significant in older patients (≥70 years), non-ST elevation, and female, while there was a decreasing trend mortality rate in ST elevation and young patients; no significant trend was observed in male. Strikingly, there is an alarming increase in the rate of haemorrhagic stroke (APC 3.4% [2.3 to 4.4], P Conclusions Patients with MI have evolved to be older and more comorbid. Alarmingly, despite reduction in long-term all-cause death over time, the reduction was small; risk of death in short-term significantly increased and patients suffer from more complications including haemorrhagic stroke and pneumonia. These results highlight the emergence of extra-cardiac outcomes that drive poor prognosis and accentuate the need to develop tailored strategies to tackle these potentially lethal complications. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): The Shenzhen Key Medical Discipline; The Sanming Project of HKU-SZH Cardiology

Background A substantial proportion of patients with acute coronary syndrome (ACS) may have intermediate lesion that are non-ischemic during emergency coronary angiography. The prognosis of such patients, compared to those with stable ischemic heart disease (SIHD) without ischemic lesion is however uncertain. Recently, a novel index, computational pressure-flow dynamics derived fractional flow reserve (caFFR), has been developed to assess myocardial ischemia, without the need of invasive pressure wire and hyperaemic stimulus as required in conventional fractional flow reserve (FFR). By utilizing caFFR to assess for ischaemic status during coronary angiography, the aim of our study is first to assess the prognostic difference between ACS and SIHD with non-ischaemia intermediate lesions. Second, we ascertain whether PCI in patients with ACS with non-ischaemia intermediate lesions provides survival benefit in addition to medical therapy. Methods We retrospectively recruited 551 patients (mean age 64.4 years; male 59.9%) with absence of myocardial ischaemia, defined as caFFR ≥0.80 in all vessels, from our Hospital. Patients were stratified into those with index presentation of ACS (n=132) and those with SIHD (n=491). Among the ACS cohort, patients were further divided into those with PCI (n=83) and with medical therapy alone (n=49). The SIHD cohort (n=491), all of whom were treated with medical therapy alone, was considered as referent group. The primary end point was major adverse cardiovascular events (MACE) at 3 years, which was defined as a composite of all-cause mortality, non-fatal myocardial infarction (MI), and any unplanned revascularization. Results During a median follow-up of 36 months, 54 composite events occurred, including 38 all-cause mortality, 5 MI, and 14 unplanned revascularization. Compared to those with SIHD, patients with ACS was independently associated with MACE even in the absence of myocardial ischaemia (adjusted Hazard Ratios=2.531; 95% confidence interval=1.397–4.586; P=0.002). The 3-year incidence rate of MACE was the highest in ACS patients with medical therapy alone, followed by ACS patients with immediate PCI; the SIHD cohort had the lowest incidence rates (30.6% vs 12.0% vs 5.9%, P Conclusion In patients with intermediate lesion without myocardial ischaemia (defined as caFFR ≥0.8), those presented with ACS had a higher risk of MACE at 3 years compared to SIHD. Among ACS patients with intermediate lesion without myocardial ischaemia, PCI significantly reduces the rate of MACE. In patients with ACS, our finding suggests that PCI should be advocated to intermediate lesion even without myocardial ischaemia. Funding Acknowledgement Type of funding sources: None. Kaplan-Meier curve for MACECumulative Events at 3 Years

Type 2 diabetes is associated with an increased risk of hip fractures. We hypothesize that long-term glycemic variability predicts incident hip fractures. We demonstrated that HbA1c variability predicted incident hip fractures independent of mean HbA1c, suggesting the potential benefits of minimizing glycemic variability in addition to optimizing mean glycemia for bone health.Type 2 diabetes is associated with an increased risk of hip fractures, and a linear relationship between HbA1c levels and hip fracture incidence has been observed. We hypothesize that HbA1c variability also predicts incident hip fractures in type 2 diabetes.Chinese individuals with type 2 diabetes aged ≥ 60 years were identified from electronic health records in Hong Kong between 2008 and 2012 and observed for incident hip fractures. Hip fracture was defined by the International Classification of Diseases (Ninth Revision) code 820. HbA1c variability was determined using standard deviation, adjusted standard deviation, and coefficient of variation of HbA1c measurements in the 5 years preceding the entry date. Multivariable Cox regression analysis was used to evaluate associations between HbA1c variability and incident hip fractures.A total of 83,282 participants were included. Their mean age was 71.3 ± 7.5 years, duration of diabetes 11.7 ± 7.7 years, baseline HbA1c 56.6 ± 13.5 mmol/mol (7.33 ± 1.23%), and median follow-up 6.8 years. All indices of HbA1c variability were significant independent predictors of incident hip fractures, with an adjusted hazard ratio of up to 1.29 (all p 0.001), and remained to be independent predictors across groups of different intensity of glycemic control. Mean HbA1c ≥ 64 mmol/mol (8.0%) was associated with a 25% increase in incident hip fractures compared with mean HbA1c 53 mmol/mol (7.0%).HbA1c variability is an independent positive predictor of hip fracture in type 2 diabetes, across the spectrum of varying degree of glycemic control, while a high HbA1c is also not advisable from the perspective of bone health.

Background Few prospective studies have evaluated sex-specific pattern, natural progression of left ventricular (LV) remodeling and diastolic dysfunction in patients with type 2 diabetes (T2DM). Purpose The aim of this study was to study the sex-specific prevalence, longitudinal changes of LV remodeling and diastolic dysfunction in patients with T2DM. Further the prognostic value of diastolic function in women and men was also evaluated. Methods A total of 386 patients with T2DM (mean age 61±11 years; women, 48.2%) was recruited. Detailed echocardiography was performed and LV geometry, systolic and diastolic function were measured at baseline and follow-up. A major adverse cardiovascular event (MACE) was defined as cardiovascular death, heart failure hospitalization or myocardial infarction. Multivariable cox-regression adjusted for age, hypertension, LVEF and HbA1c was used to assess the association between sex-specific diastolic function and the development of a MACE. Results Despite a similar age, prevalence of hypertension and body mass index, women had a higher prevalence of LV hypertrophy and diastolic dysfunction at baseline and follow-up compared with men. A total of 26 patients developed a MACE (4 cardiovascular death, 14 hospitalization for heart failure, 8 myocardial infarction) during follow-up. Women with diastolic dysfunction had a higher incidence of MACE than those with normal diastolic function but this association was neutral in men. Multivariable Cox-regression analysis indicated that diastolic dysfunction was associated with MACE in women (hazard ratio 6.35, 95% confidence interval 1.18–34.19, P Conclusions LV hypertrophy and diastolic dysfunction, both at baseline and follow-up, were more common in women than men. Pre-clinical diastolic dysfunction was independently associated with MACE only in women with T2DM but was neutral in men.

This review article summarises the sources, occurrence, fate and effects of plastic waste in the marine environment. Due to its resistance to degradation, most plastic debris will persist in the environment for centuries and may be transported far from its source, including great distances out to sea. Land- and ocean-based sources are the major sources of plastic entering the environment, with domestic, industrial and fishing activities being the most important contributors. Ocean gyres are particular hotspots of plastic waste accumulation. Both macroplastics and microplastics pose a risk to organisms in the natural environment, for example, through ingestion or entanglement in the plastic. Many studies have investigated the potential uptake of hydrophobic contaminants, which can then bioaccumulate in the food chain, from plastic waste by organisms. To address the issue of plastic pollution in the marine environment, governments should first play an active role in addressing the issue of plastic waste by introducing legislation to control the sources of plastic debris and the use of plastic additives. In addition, plastics industries should take responsibility for the end-of-life of their products by introducing plastic recycling or upgrading programmes.

Mercury (Hg) has long been recognised as a global pollutant, because it can remain in the atmosphere for more than 1 year. The mercury that enters the environment is generally acknowledged to have two sources: natural and anthropogenic. Hg takes three major forms in the environment, namely methyl-Hg (MeHg), Hg(0) and Hg(2+). All three forms of Hg adversely affect the natural environment and pose a risk to human health. In particular, they may damage the human central nervous system, leading to cardiovascular, respiratory and other diseases. MeHg is bioavailable and can be bioaccumulated within food webs. Therefore, several methods of eliminating Hg from the soil and the aquatic system have been proposed. The focus of this article is on phytoremediation, as this technique provides a low-cost and environmentally friendly alternative to traditional methods.

The Gemini-AALA (Australia, Asia, Latin America, Africa/Middle East) study evaluated the efficacy and safety of single-pill amlodipine/atorvastatin (Caduet) for the treatment of patients of diverse ethnicity with concomitant hypertension and dyslipidaemia. This was a 14-week, open-label study including patients from 27 countries across the Middle East, Asia-Pacific, Africa and Latin America. Eight dosage strengths of single-pill amlodipine/atorvastatin (5/10, 10/10, 5/20, 10/20, 5/40, 10/40, 5/80 and 10/80 mg) were titrated to improve blood pressure and lipid control. Blood pressure and lipid goals were determined according to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) and National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP ATP III) guidelines, respectively (blood pressure,140/90 or130/80 mm Hg; low-density lipoprotein cholesterol (LDL-C),4.1 to2.6 mmol l(-1) (160 to100 mgdl(-1))). Overall, 1649 patients received study medication. Most patients (91.4%) hador=1 cardiovascular risk factor (as defined by NCEP ATP III guidelines) in addition to hypertension/dyslipidaemia, and 61.7% had coronary heart disease/risk equivalent. At baseline, mean blood pressure was 146.6/88.3 mm Hg and LDL-C was 3.4 mmol l(-1) (130.2 mgdl(-1)). At week 14, 55.2% of patients reached both blood pressure and lipid goals, 61.3% reached blood pressure goal and 87.1% reached lipid goal (34.0% were at lipid goal at baseline). Mean blood pressure reduction was 20.2/11.4 mm Hg. For patients who were lipid-lowering drug naive at baseline, mean reduction in LDL-C was 41.0%. Treatment-related adverse events led to the discontinuation of 3.6% of patients. Single-pill amlodipine/atorvastatin therapy was well tolerated and effective for the reduction of blood pressure and lipids to recommended goals in patients from diverse ethnic backgrounds.

Advances in differentiation of cardiomyocytes from human induced pluripotent stem cell (hiPSC) were emerged as a tool for modeling of cardiovascular disease that recapitulates the phenotype for the purpose of drug screening, biomarker discovery, and testing of single-nucleotide polymorphism (SNP) as a modifier for disease stratification. Here, we describe the (1) retroviral reprogramming strategies in the generation of human iPSC, (2) methodology in characterization of iPSC in order to identify the stem cell clones with the best quality, and (3) protocol of cardiac differentiation by modulation of Wnt signaling and β-catenin pathway.

OBJECTIVES. To evaluate attainment of low-density lipoprotein cholesterol goals among hypercholesterolaemic patients undergoing lipid-lowering drug treatment in Hong Kong and to identify potential determinants of treatment outcomes. DESIGN. Cross-sectional observational study. SETTING. A single site in Hong Kong, as part of the CEPHEUS Pan-Asian survey. PATIENTS. Subjects with hypercholesterolaemia aged 18 years or above, who had been on lipid-lowering drug treatment for at least 3 months with no dose adjustment for at least 6 weeks. RESULTS. A total of 561 such patients (mean age, 65.3; standard deviation, 9.7 years) were evaluated. Most had major cardiovascular risk factors; 534 (95.2%) of 561 patients had coronary heart disease and 534 (95.4%) of 560 patients had low-density lipoprotein cholesterol goals set at lower than 70 mg/dL. In all, 465 (82.9%) patients attained their respective low-density lipoprotein cholesterol goals. Among 75 patients who had coronary heart disease or equivalent risk, and multiple risk factors with a 10-year coronary heart disease risk of over 20%, 62 (82.7%) attained their respective low-density lipoprotein cholesterol goals. Significant predictors of low-density lipoprotein cholesterol goal attainment included the patient's baseline lipid profile (total cholesterol and low-density lipoprotein cholesterol levels), blood pressure, and drugs (statin/non-statin) used for treatment. CONCLUSIONS. Hypercholesterolaemic patients undergoing lipid-lowering drug treatment in the present Hong Kong study were able to achieve a very high attainment rate for the low-density lipoprotein cholesterol goal, despite the fact that most of them had major cardiovascular risk factors.

Previous studies demonstrated that high fruit consumption was associated with a lower risk of cardiovascular events in patients with Type 2 diabetes mellitus. However, the relationship between fruit intake and carotid atherosclerosis in these patients is unknown. We studied the relationship between dietary fruit intake and carotid intima-media thickness in patients with Type 2 diabetes.A total of 255 Chinese patients with Type 2 diabetes were recruited. Dietary fruit intake was assessed by a validated food-frequency questionnaire, and carotid intima-media thickness was measured by high-resolution ultrasonography.Among patients with three different tertiles of fruit intake (14.5 ± 8.6 vs. 41.5 ± 7.1 vs. 92.6 ± 39.7 g/day), there was no difference in their clinical characteristics (all P0.05). Patients with the highest tertile of fruit intake had a significantly higher BMI and diastolic blood pressure than those with the lowest tertile intake. Furthermore, serum high-sensitivity C-reactive protein, 8-isoprostane and superoxide dismutase were similar among the three tertiles of patients (all P0.05). However, patients with the highest tertile of fruit intake had lower carotid intima-media thickness (0.97 ± 0.02 vs. 1.08 ± 0.03 mm, P = 0.046) and prevalence of carotid plaque (11.76 vs. 1.18%, P = 0.022) than those with the lowest tertile of fruit intake. Multivariate regression analysis revealed the highest tertile of fruit intake (β = -0.086, P = 0.049) was independently associated with carotid intima-media thickness.Our results demonstrated that, in Chinese patients with Type 2 diabetes, higher dietary fruit intake was associated with a lower burden of carotid atherosclerosis as reflected by lower carotid intima-media thickness and prevalence of carotid plaque.

To study the predictive value of coronary calcification score (CCS) for future cardiovascular (CVS) events as detected by multi-detector computed tomography (MDCT) in patients with rheumatoid arthritis(RA) and systemic lupus erythematosus (SLE).A total of 152 patients with RA and SLE, and 106 healthy controls underwent MDCT to measure CCS. All patients were prospectively followed up for major CVS events.Compared with controls, patients with RA and SLE had a significantly higher mean CCS (42.2±154.3 vs. 1.4±13.0, p0.01) and prevalence of CCS 1-10, CCS 11-100 and CCS100 (all p0.05). After a mean period of 4.3±0.6 years, major CVS events occurred in 10 patients with RA and SLE. In patients with RA and SLE, a higher major CVS events rate occurred in patients with CCS 1-10 (5.0%), CCS 11-100 (14.3%) and CCS100 (40.0%) than those with CCS=0 (1.0%, p0.01). Multivariate Cox regression analysis revealed that hypercholesterolemia (hazard ratio (HR) 11.2, confidence interval (CI 1.4-89.3, p=0.02) and CCS100 (HR 11.1, CI 1.31-95.0, p=0.03) were independent predictors of combined events.Coronary calcification detected by MDCT independently predicts CVS events in patients with RA and SLE. Risk stratification by assessment of CCS may have an important role in patients with systemic inflammatory disease.

Psoriasis is associated with premature atherosclerosis although the underlying mechanism remains unclear.We sought to investigate the relationship between disease activity and systemic inflammation in patients with psoriasis, and macrovascular and microvascular function.Fifty-two patients with psoriasis (mean ± SD age 44 ± 8 years; 38 men) were compared with 50 age- and sex-matched controls. Baseline demographics and high-sensitivity C-reactive protein (hs-CRP) level were recorded for each subject. Psoriatic disease activity was assessed using the Psoriasis Area and Severity Index (PASI). Arterial stiffness and endothelial function were assessed using brachial to ankle pulse wave velocity (baPWV) and digital hyperaemic response measured using the peripheral arterial tonometry (PAT) index.Patients with psoriasis had significantly higher hs-CRP (mean ± SD 5·3 ± 5·1 vs. 1·9 ± 1·6 mg L(-1), P0·01) and baPWV (mean ± SD 14·5 ± 2·5 vs. 13·2 ± 1·6 m s(-1) , P0·01) but not PAT index (mean ± SD 2·06 ± 0·59 vs. 2·10 ± 0·44, P = 0·70) than controls. There was significant correlation of hs-CRP with baPWV (r = 0·51, P0·01) and with PASI (r = 0·48, P0·01). Multiple linear regression analysis demonstrated that baPWV is independently correlated with age, fasting glucose and hs-CRP (P0·05), but does not predict PAT index. Each mg L(-1) increase in hs-CRP accounted for an increase in baPWV of +0·12 m s(-1) (95% confidence interval 0·01-0·22, P = 0·03).Young patients with psoriasis have increased arterial stiffness but not microvascular dysfunction compared with healthy controls. More importantly, hs-CRP positively correlated with, and independently predicted, arterial stiffness. This suggests that systemic inflammation in patients with psoriasis is associated with premature atherosclerosis.

Results of previous studies on the level of circulating endothelial progenitor cells (EPCs), which are involved in vascular repair, in scleroderma (SSc) patients have been controversial.To enumerate circulating EPC subsets and to examine their relation with endothelial dysfunction, biochemical markers of endothelial injury and vascular outcome in SSc patients.Enumeration of circulating CD34+KDR+ and CD133+ KDR+EPCs was performed by flow cytometry. Endothelium-dependent vasodilation was evaluated by changes in flow-mediated dilation (FMD%) in the brachial artery. Serum level of vascular endothelial growth factor (VEGF) was measured by enzyme linked immunosorbent assay.SSc patients (n=52) were found to have significantly lower CD133+KDR+EPCs (3.0 vs. 7.0/μl, p0.001) as well as FMD% (4.8% vs. 7.8%, p0.001) compared with age and sex-matched controls (n=52). Among patients who had no concomitant cardiovascular risk factors (n=28), CD133+KDR+ EPC level was significantly lower than controls (3.8 vs. 7.3/μl, p=0.001) and correlated modestly with FMD% (r=0.29, p=0.03). Disease duration was the only determining factor identified for circulating CD133+KDR+ EPCs (p=0.03) by logistic regression analysis. Levels of serum VEGF (p=0.92) and KDR expression were not different between patients who had early and intermediate/late disease. Circulating CD34+KDR+ EPCs was not different between SSc patients and controls and did not correlate with any clinical or biochemical parameter.Lower circulating CD133 +KDR+ EPC subset was found in SSc patients and correlated with impaired endothelium-dependent vasodilation in patients without cardiovascular risk factors suggesting a potential role of deficient EPC recruitment contributing to endothelial dysfunction in this disease.

Increased dietary fish-oil consumption is associated with a reduced risk of coronary heart events and has pronounced effects on dyslipidaemia. However, the effects of fish-oil supplement on vascular function and metabolic profile in patients with Type 2 diabetes mellitus (DM) are unclear.In a double-blind placebo-controlled trial, we randomized 97 Type 2 DM patients without prior cardiovascular disease to fish-oil (4 g/day, n = 49) or olive-oil (with equivalent calories, as placebo, n = 48) supplements for 12 weeks. Assessment of vascular function with brachial artery flow-mediated dilation (FMD) and circulating levels of endothelial progenitor cells (EPCs), and metabolic parameters, high-sensitivity C-reactive protein (hsCRP), oxidative stress markers and renal function were examined before and after the supplement.Despite a significant reduction in serum triglycerides (-0.47 mmol/l, P0.01), 12-week supplement of fish oil did not improve vascular function as determined by FMD (+0.16%, P = 0.83) and circulating EPC count (+4 cells/microl, P = 0.78). Furthermore, fish-oil supplement did not have any significant treatment effects on hsCRP, oxidative stress, low- and high-density lipoprotein and glycated haemoglobin (HbA(1c)) (all P0.05). In contrast, serum creatinine was lower (-4.5 micromol/l, P = 0.01) in fish-oil-treated patients as compared with control subjects.This study demonstrated that 12 weeks of fish-oil supplement had no significant beneficial effect on vascular endothelial function, but improved renal function without changes in endothelial function, metabolic profiles, blood pressure, inflammation or oxidative stress in patients with Type 2 DM.

Compared with anterior wall myocardial infarction, inferior wall myocardial infarction is generally regarded as being low risk. The aim of this study was to elucidate the clinical factors affecting its inhospital outcome.From January 1997 to March 2006, 546 consecutive patients who suffered from their first inferior wall myocardial infarction were recruited for the study. The demographic, clinical, electrocardiographical and angiographical characteristics, treatment and medications, complications and inhospital deaths were subjected to univariate analysis. The factors that had a p-value of less than 0.1 were included for multivariate logistic regression analysis. A p-value of less than 0.05 was considered significant. The impact of thrombolysis on clinical outcome in various high-risk patient subsets was also examined.An advanced age of more than 74 years, female gender, lateral wall extension, complete atrioventricular block, bundle branch block, and cardiac free-wall rupture were found to be independent predictors of inhospital mortality, whereas the use of thrombolysis was associated with a favourable outcome. On the other hand, right ventricular infarction and precordial ST-segment depression are not predictive of poor outcome. In addition, thrombolysis reduced inhospital mortality in patients with an age above 64 years, male gender, lateral wall extension, haemodynamically-significant right ventricular infarction and complete atrioventricular block.In inferior wall myocardial infarction, independent predictors of poor inhospital outcome are advanced age, female gender, lateral wall extension, complete atrioventricular block, bundle branch block and cardiac free-wall rupture. The use of thrombolysis is generally beneficial, especially in those of the high-risk subsets.

Ketanserin, a selective 5-HT receptor antagonist, prolongs the QT interval of ECG in patients. The purpose of the present study was to determine whether ketanserin would block human cardiac ether-à-go-go-related gene (hERG) potassium channels.Whole-cell patch voltage-clamp technique was used to record membrane currents in HEK 293 cells expressing wild type or mutant hERG channel genes.Ketanserin blocked hERG current (I(hERG)) in a concentration-dependent manner (IC50=0.11 microM). The drug showed an open channel blocking property, the block increasing significantly at depolarizing voltages between +10 to +60 mV. Voltage-dependence for inactivation of hERG channels was negatively shifted by 0.3 microM ketanserin. A 2.8 fold attenuation of inhibition by elevation of external K+ concentration (from 5.0 to 20 mM) was observed, whereas the inactivation-deficient mutants S620T and S631A had the IC50s of 0.84 +/- 0.2 and 1.7 +/-0.4 microM (7.6 and 15.4 fold attenuation of block). In addition, the hERG mutants in pore helix and S6 also significantly reduced the channel block (2-59 fold) by ketanserin.These results suggest that ketanserin binds to and blocks the open hERG channels in the pore helix and the S6 domain; channel inactivation is also involved in the blockade of hERG channels. Blockade of hERG channels most likely contributes to the prolongation of QT intervals in ECG observed clinically at therapeutic concentrations of ketanserin.

Paracrine effect is the major mechanism that underlies mesenchymal stem cells (MSC)-based therapy. This study aimed to examine how Rap1, telomeric repeat-binding factor 2-interacting protein 1 (Terf2IP), which is a novel modulator involved in the nuclear factor-kappaB (NF-κB) pathway, regulates the paracrine effects of MSC-mediated heart repair following infarction. NF-κB activity of stromal cells was increased by Rap1 as measured by pNF-κB-luciferase reporter activity, and this was abolished by IkB-dominant-negative protein. Knockdown of Rap1 with shRap1 resulted in diminished translocation of p65-NF-κB from the cytoplasm to nuclei in response to tumor necrosis factor-α (TNF-α) stimulation. Compared with BM-MSCs, Rap1−/−-BM-MSCs displayed a significantly reduced ratio of phosphorylated NF-κB to NF-κB-p65 and of Bax to Bcl-2, and increased resistance to hypoxia-induced apoptosis by the terminal deoxynucleotidal transferase-mediated dUTP nick end labeling (TUNEL) assay. In contrast, re-expression of Rap1 in Rap1−/−-BM-MSCs resulted in loss of resistance to apoptosis in the presence of hypoxia. Moreover, absence of Rap1 in BM-MSCs led to downregulation of NF-κB activity accompanied by reduced pro-inflammatory paracrine cytokines TNF-α, IL (interleukin)-6 and monocyte chemotactic protein-1 in Rap1−/−-BM-MSCs compared with BM-MSCs. The apoptosis of neonatal cardiomyocytes (NCMCs) induced by hypoxia was significantly reduced when cocultured with Rap1−/−-BM-MSC hypoxic-conditioned medium (CdM). The increased cardioprotective effects of Rap1−/−-BM-MSCs were reduced when Rap1−/−-BM-MSCs were reconstituted with Rap1 re-expression. Furthermore, in vivo study showed that transplantation of Rap1−/−-BM-MSCs significantly improved heart function, decreased infarct size, prevented cardiomyocyte apoptosis and inhibited inflammation compared with controls and BM-MSCs (P−/−-BM-MSCs decreased NF-κB sensitivity to stress-induced pro-inflammatory cytokine production and reduced apoptosis. Selective inhibition of Rap1 in BM-MSCs may be a novel strategy to enhance MSC-based therapeutic efficacy in myocardial infarction.

Recent prospective clinical trials have demonstrated that physiologic pacing mode reduces the risk of atrial fibrillation (AF) compared to single chamber ventricular pacing in patients with sick sinus syndrome (SSS).1–3 Previous studies have shown that patients with a prior history of AF before pacemaker implant are associated with an increase risk of persistent AF.3 Recent advances in the ability to store diagnostic information in implanted devices have provided an opportunity for detection and documentation of AF. The aim of this study was to define the prevalence and clinical significance of device detected AF episodes in patients implanted with pacemakers for SSS. We studied the clinical characteristics and long term clinical outcome in patients with SSS who had received a dual chamber rate responsive pacemaker (DDDR) for symptomatic bradycardia in our institutions from 1992 to 1998. Patients were eligible if they received a DDDR pacemaker which was capable of providing diagnostic counters for supraventricular tachyarrhythmias and was programmed “ON”. P wave analysis was manually measured by a single investigator. A surface echocardiogram was performed in all patients before implant to assess left atrial size, left ventricular ejection fraction, and left ventricular mass. Data were retrospectively collected regarding demographic characteristics, device diagnostics, clinical status, and outcome during the follow up period. Clinical data were retrieved from the medical records and subsequently during the most recent clinic visit. The …

Sudden cardiac death remains a major health issue in western countries as well as in Hong Kong. Despite increasing knowledge of the mechanisms and risk factors of sudden cardiac death, methods for identifying high-risk candidates and predicting the efficacy of measures to prevent sudden cardiac death are still inadequate. A significant proportion of patients have known heart disease but are generally considered to be at low risk for this event. More efforts are needed to improve the success rate of out-of-hospital resuscitation through better warning systems, the use of amiodarone for refractory arrhythmias, and the widespread availability of automated defibrillation devices to allow early defibrillation. It is likely that these measures could increase the number of survivors following cardiac arrest. In survivors of sudden cardiac death episodes, treatment of the underlying cardiac disease, especially early revascularisation for myocardial ischaemia, is required. In the majority of patients, implantation of an implantable cardioverter defibrillator, with or without the use of an anti-arrhythmic drug such as amiodarone, would then be used to maintain survival. Furthermore, for individuals at significant risk of sudden cardiac death, primary prevention of sudden cardiac death through the placement of an implantable cardioverter defibrillator is increasingly being used.

To evaluate high-resolution CT (HRCT) parameters of inflammation and fibrosis in systemic sclerosis (SSc), for correlation with lung function, skin scores and exercise tolerance.45 SSc patients (40 women, 48.5+/-13.4 years), underwent thoracic HRCT, lung function assessment, and modified Rodnan skin scores. Exercise tolerance was also graded. HRCT were scored for extent of 4 HRCT patterns of interstitial lung disease (ILD): ground glass opacification (GGO), reticular, mixed and honeycomb pattern in each lobe. Total HRCT score, inflammation index (GGO and mixed score) and fibrosis index (reticular and honeycomb scores) were correlated with lung function and clinical parameters.ILD was present in 39/45 (86.7%) patients. Abnormal (80% predicted) forced vital capacity (FVC), total lung capacity (TLC) and carbon monoxide diffusion factor (DLco) were detected in 30%, 22% and 46% of patients. Total HRCT score correlated with FVC (r=-0.43, p=0.008), FEV1 (forced expiratory volume) (r=-0.37, p=0.03), TLC (r=-0.47, p=0.003), and DLCO (r=-0.43, p=0.008); inflammatory index with DLCO (r=-0.43, p=0.008) and exercise tolerance (r=-0.39, p0.05); and fibrosis index with FVC (r=-0.31, p=0.05) and TLC (r=-0.38, p=0.02). Higher total HRCT score, and inflammation and fibrosis indices were found in patients with abnormal lung function.Qualitative HRCT is able to evaluate inflammation and fibrosis, showing important relationships with diffusion capacity and lung volume, respectively.

Japan Tobacco is developing the mixed action ion channel blocker, JTV-519, which has potential use as an antiarrhythmic [285800]. The drug is a novel cardioprotectant derivative of 1,4-benzothiazepine for which phase I trials were completed in the third quarter of 1998; phase II trials started in the fourth quarter of 1998 for the potential treatment of myocardial infarction [320195]. Studies have shown that JTV-519 has a strong cardioprotective effect against catecholamine-induced myocardial injury and against ischemia/reperfusion injury [316749]. In experimental myofibrillar overcontraction models, it demonstrated greater cardioprotectant effects than propranolol, verapamil and diltiazem [171668].

Recent studies have demonstrated that premature depolarizations that trigger atrial fibrillation often arise in pulmonary veins. The purpose of this study was to evaluate whether P wave polarity is helpful in distinguishing which of the 4 pulmonary veins is the site of origin of a premature depolarization.In 28 patients without structural heart disease who underwent focal ablation of paroxysmal atrial fibrillation, P wave polarity on a 12-lead electrocardiogram (ECG) was analyzed during sinus rhythm, and during pacing at a cycle length of 500--600 ms in the high right atrium and within each of the 4 pulmonary veins. P waves were categorized as positive, negative, biphasic or isoelectric. A negative or biphasic P wave in lead I (sensitivity 85 %, specificity 71 %) or a positive P wave in V1 (sensitivity 85 %, specificity 89 %) were helpful in predicting a pulmonary venous site of origin as opposed to a right atrial site of origin. A positive P wave in lead II and III distinguished superior from inferior pulmonary veins (sensitivity 90 %, specificity 84 %). The sensitivity and specificity of negative or biphasic P waves in lead aVL in distinguishing a left from right pulmonary vein site of origin were 94 % and 42 %, respectively.Analysis of P waves polarity may be helpful in localizing the pulmonary vein that is the site of origin of a premature depolarization. Among the 12 ECG leads, I, II, III, aVL, and V1 are the most helpful in regionalizing premature depolarizations arising in the pulmonary veins.

The use of single lead for atrial synchronous ventricular (VDD) pacing in patients with high grade atrioventricular (AV) block and normal sinus node function is an acceptable alternative to dual chamber (DDD) pacing. Implantation and follow up procedures are simplified, and cost is usually reduced by more than the cost of an additional atrial lead. With the use of either diagonally arranged dipole or closely spaced ring electrodes, reliable atrial sensing can be achieved using differential atrial amplifier and high atrial sensitivity. Also oversensing is infrequently observed using provocation tests and dynamic recordings, clinical undersensing is unusual and minimized by programming to the highest atrial sensitivity. However, as atrial pacing is not possible, loss of AV synchrony and rate response may occur for unrecognized or progressive sinus node disease and lower rate limit. The development of single lead dual chamber pacing system may overcome this limitation. Recent studies have demonstrated that atrial pacing can be effective either with the use of a special pacing lead configuration or via floating atrial electrode with a novel stimulation method. Overlapping biphasic impulse (OLBI) can reduce atrial pacing threshold. Early clinical experience suggested that this new pacing method can provide effective and reliable atrial pacing with a relatively low incidence of diaphragmatic pacing. Thus the problem of atrial sensing is solved with a single pass lead but further long term evaluation is required to assess the efficacy and feasibility of new instrumentation for single lead dual chamber pacing.

Pulmonary hypertension (PHT) associated with systemic lupus erythematosus (SLE) has a dismal prognosis. Vasodilators and immunosuppressive therapy have been tried over the years with discouraging results. Prostacyclin (PGI2) which has potent vasodilatatory and anti-platelet effects has been demonstrated to significantly decrease pulmonary arterial pressure and pulmonary vascular resistance during acute infusion. Satisfactory response has been reported in SLE patients with PHT treated with short-term intravenous continuous PGI2 infusion. We report here a 48-month experience of the use of monthly low dose infusion of a PGI2 analogue, iloprost, in a SLE patient with pulmonary hypertension in New York Heart Association functional Class III. There was an initial haemodynamic response to an acute infusion of iloprost. Repeated infusions were followed by marked improvement in her functional status and her mean pulmonary arterial pressure dropped from 80 mmHg in the first few months and remained static at around 55 mmHg for the subsequent years.

The long-term efficacy of atrial fibrillation (AF) detection and R-wave synchronization are critical safety requirements for the development of an implantable atrial defibrillator (IAD) for treatment of AF.The long-term efficacy of the Metrix IAD for AF detection and R-wave synchronization was tested in 51 patients. The mean duration of follow-up was 259+/-138 days (72 to 613 days). AF detection tests were performed 2240 times during observed operation with 100% specificity and 92.3% sensitivity for differentiation between sinus rhythm and AF; 2219 episodes and their electrograms stored in the device during AF detection were analyzed. The positive predictive value of the AF detection algorithm was 97.4% (lower 95% confidence limit [CL], 94.5%) in the out-of-hospital setting. A total of 242 435 R waves were analyzed for R-wave synchronization. Of these, 49% were marked for synchronized shock delivery, 82% of sinus rhythm and 36% of AF R waves, respectively. All shock markers were properly synchronized and within the R wave (overall synchronization accuracy, 100%; lower 95% CL, 99.999%). Overall, 3719 shocks have been delivered via the IAD with no instance of unsynchronized shock delivery or any episode of proarrhythmia. The observed proarrhythmic risk was 0%, with an estimated maximum proarrhythmic risk of 0.084% per shock (95% upper CL).The Metrix IAD can appropriately detect AF with a high specificity and sensitivity and reliably synchronize within a suitable R wave for shock delivery to minimize the risk of ventricular proarrhythmia.