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.

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.

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.

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.

Point-of-care ultrasound augments physical examination learning by undergraduate medical students.

BACKGROUND: Little is known about the impact of the provision of handheld point-of-care ultrasound (POCUS) devices on physical examination skills of medical students. METHODS: We describe an educational initiative that comprised a POCUS workshop followed by allocation of a POCUS device to medical students for use over the subsequent 8 weeks. They were encouraged to scan patients and correlate their physical examination findings. A mobile instant messaging group discussion platform was set to provide feedback from instructors. Physical examination skills were assessed by means of clinical examination. RESULTS: 210 final-year medical students from the University of Hong Kong participated in the programme. 46.3% completed the end of programme electronic survey: 74.6% enjoyed using the POCUS device, 50.0% found POCUS useful to validate physical examination findings and 47.7% agreed that POCUS increased their confidence with physical examination. 93.9% agreed that the programme should be incorporated into the medical curriculum and 81.9% would prefer keeping the device for longer time from 16 weeks (45.6%) to over 49 weeks (35.3%). Medical students who participated in the POCUS programme had a higher mean score for abdominal examination compared with those from the previous academic year with no POCUS programme (3.65±0.52 vs 3.21±0.80, p=0.014), but there was no statistically significant difference in their mean score for cardiovascular examination (3.62±0.64 vs 3.36±0.93, p=0.203). CONCLUSION: The POCUS programme that included provision of a personal handheld POCUS device improved students' attitude, confidence and ability to perform a physical examination.

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.

Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention of Recurrent Cardiovascular Events in a Real-World Cohort of Post-Acute Myocardial Infarction Patients.

BACKGROUND: Patients who survive myocardial infarction (MI) are at risk of recurrent cardiovascular (CV) events. This study stratified post-MI patients for risk of recurrent CV events using the Thrombolysis in Myocardial Infarction (TIMI) Risk Score for Secondary Prevention (TRS 2°P). Methods and Results: This was an observational study that applied TRS 2°P to a consecutive cohort of post-MI patients. The primary outcome was a composite endpoint of CV death, non-fatal MI, and non-fatal ischemic stroke. A total of 1,688 post-MI patients (70.3±13.6 years; male, 63.1%) were enrolled. After a mean follow-up of 41.5±34.4 months, 405 patients (24.0%) had developed a primary outcome (9.3%/year) consisting of 278 CV deaths, 134 non-fatal MI, and 33 non-fatal strokes. TRS 2°P was strongly associated with the primary outcome. The annual incidence of primary composite endpoint for patients with TRS 2°P 0 was 1.0%, and increased progressively to 39.9% for those with TRS 2°P ≥6 (HR, 27.6; 95% CI: 9.87-77.39, P<0.001). The diagnostic sensitivity of TRS 2°P for the primary composite endpoint was 76.3% (95% CI: 72.1-80.5%). Similar associations were also observed between TRS 2°P and CV death and non-fatal MI, but not non-fatal ischemic stroke. CONCLUSIONS: TRS 2°P reliably stratified post-MI patients for risk of future CV events.

Rationale and design of the screening of pulmonary hypertension in systemic lupus erythematosus (SOPHIE) study.

Current guideline-recommended screening for pulmonary hypertension in patients with systemic sclerosis has not been evaluated in systemic lupus erythematosus (SLE), which is disproportionately prevalent in Asians. This multicentre, cross-sectional screening study aims to study the prevalence of pulmonary hypertension among SLE patients using these guidelines, and identify independent predictors and develop a prediction model for pulmonary hypertension in SLE patients. SLE patients from participating centres will undergo an echocardiography- and biomarker-based pulmonary hypertension screening procedure as in the DETECT study. Standard right heart catheterisation will be provided to patients with intermediate or high echocardiographic probability of pulmonary hypertension. Those with low echocardiographic probability will rescreen within 1 year. The primary measure will be the diagnosis and types of pulmonary hypertension and prevalence of pulmonary hypertension in SLE patients. The secondary measures will be the predictors and prediction models for pulmonary hypertension in SLE patients. The estimated sample size is approximately 895 participants. The results of the SOPHIE study will be an important contribution to the literature of SLE-related pulmonary hypertension and may be immediately translatable to real clinical practice. Ultimately, this study will provide the necessary evidence for establishing universal guidelines for screening of pulmonary hypertension in SLE patients.

Impact of provision of time in therapeutic range value on anticoagulation management in atrial fibrillation patients on warfarin.

INTRODUCTION: The importance of time in therapeutic range (TTR) in patients prescribed warfarin therapy for stroke prevention in atrial fibrillation (AF) cannot be overemphasised. AIM: To evaluate the impact of provision of TTR results during clinic visits on anticoagulation management. DESIGN: Single-centred, randomised controlled study. SETTING: Fifteen arrhythmia clinics in Hong Kong. PATIENTS: AF patients prescribed warfarin. INTERVENTIONS: Provision of TTR or no provision of TTR. MAIN OUTCOME MEASURES: A documented discussion between doctors and patients about switching warfarin to a non-vitamin K oral anticoagulant (NOAC). RESULTS: Four hundred and eighty one patients with AF prescribed warfarin were randomly assigned to (1) a TTR provision group or (2) control. Their mean age was 73.6±12.0 years and 60.7% were men. The mean CHA2DS2-VASc score was 3.2±1.6 and the mean HASBLED score was 1.7±1.2. The mean TTR was 63.9%±29.9%. At the index clinic visit, 71 of 481 patients (14.8%) had a documented discussion about switching warfarin to a NOAC. Patients with provision of TTR results were more likely to discuss switching warfarin to a NOAC than controls (19.1% vs 10.6%, P=0.03), especially those with a TTR <65% (35.2% vs 10.6%, P<0.001). A higher proportion of patients with provision of TTR results switched to a NOAC (5.9% vs 4.1%, P=0.49). CONCLUSIONS: The provision of TTR among patients on warfarin was associated with a discussion about switching from warfarin to a NOAC in those with TTR <65%, but did not result in actual switching to a NOAC, suggesting additional barriers.

Refinement of ischemic stroke risk in patients with atrial fibrillation and CHA2 DS2 -VASc score of 1.

BACKGROUND: Patients with atrial fibrillation (AF) with CHA2 DS2 -VASc score of 1 (where CHA2 DS2 -VASc is CHA2 DS2 -Vascular disease, Age 65-74 years, Sex category) are recommended to receive antithrombotic therapy. Nonetheless, it remains unclear whether individual components that constitute CHA2 DS2 -VASc score contribute equally to the ischemic stroke risk, particularly in patients with CHA2 DS2 -VASc score of 1. The objective was to describe and compare the risk of ischemic stroke of the six individual components constituting CHA2 DS2 -VASc among AF patients with CHA2 DS2 -VASc score of 1. METHODS AND RESULTS: We studied all patients with CHA2 DS2 -VASc score of 1 and no antithrombotic therapy from our cohort of 9,727 Chinese AF patients. A total of 548 patients were studied: 190 patients with CHA2 DS2 -VASc score of 0 and 358 patients with CHA2 DS2 -VASc score of 1. Of those with a baseline CHA2 DS2 -VASc score of 1, 51.1% patients aged 65-75; 29.3% patients were female; 12.0% had hypertension; 4.5% had heart failure; 2.5% had diabetes; and 0.6% had vascular disease. After 1,758 patient-years of follow-up, the annual incidence of stroke was 2.4% and 6.6% for patients with CHA2 DS2 -VASc score of 0 and 1, respectively. Compared with patients with CHA2 DS2 -VASc score of 0, patients with hypertension leading to CHA2 DS2 -VASc score of 1 were at the highest risk of stroke (Hazard ratio [HR]: 9.8, 95% confidence interval [CI]: 2.7-35.6), followed by patients aged 65-74 (HR: 3.9, 95% CI: 2.3-6.6) and female gender (HR: 2.3, 95% CI: 1.1-4.8). Heart failure, diabetes mellitus, and vascular disease were not associated with stroke. CONCLUSION: In AF patients with CHA2 DS2 -VASc score of 1, hypertension confers the highest risk for stroke among other risk factors comprising the score. A more aggressive thromboprophylaxis strategy may be justified among AF patients with CHA2 DS2 -VASc score of 1 due to hypertension.

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.

Left ventricular mechanical dyssynchrony impairs exercise capacity in patients with coronary artery disease with preserved left ventricular systolic function and a QRS duration ≤ 120 ms.

BACKGROUND: Left ventricular (LV) mechanical dyssynchrony can lead to impairment of LV function and is associated with adverse clinical outcomes in coronary artery disease (CAD) patients. The impact of LV dyssynchrony on exercise capacity (EC) in patients with CAD was investigated. METHODS AND RESULTS: An echocardiographic examination with tissue Doppler imaging and exercise treadmill testing in 151 CAD patients with normal LV ejection fraction was performed. LV intra- and inter-ventricular dyssynchrony were defined by the standard deviation of time interval between LV 6 basal segments (Ts-SD), and the time interval from the right ventricular (RV) free wall to LV lateral wall (Ts-RV) respectively, and EC was measured as metabolic equivalents (METs) on the treadmill. Patients with impaired EC (defined by a METs ≤ 8, which is the mean MET of the study population) were older (71 ± 7 vs. 62 ± 2 years, P<0.01), however, there were no differences in gender and clinical status such as prevalence of prior myocardial infarction (MI), regional wall motion abnormality (RWMA), and coronary revascularization between patients with (n=90) or without (n=61) impaired EC. Univariate analysis showed that age, body mass index, LV systolic and diastolic volume, mitral inflow A velocity, and Ts-SD were all significantly associated with METs (all P<0.05). However, multivariate regression analysis revealed that old age (odd ratio [OR]: 1.136, 95% confidence interval [CI]: 1.080-1.196, P<0.001), and Ts-SD (OR: 1.026, 95%CI: 1.003-1.049, P=0.027) only were independent predictors for impaired EC. CONCLUSIONS: In patients with CAD, LV systolic dyssynchrony predicts impaired EC independently of history of previous MI or RWMA.

Thoracic spinal cord stimulation improves cardiac contractile function and myocardial oxygen consumption in a porcine model of ischemic heart failure.

BACKGROUND: Prior experimental studies show that thoracic spinal cord stimulation (SCS) improves left ventricular (LV) ejection fraction (LVEF). The mechanism of this improvement in the LV contractile function after SCS and its effects on the myocardial oxygen consumption remains unknown. METHODS AND RESULTS: We performed thoracic SCS (T1-T2 level) followed by 4 weeks of rapid ventricular pacing in 9 adult pigs with ischemic heart failure (HF) induced by myocardial infarction (MI). At 24 hours off-pacing, detailed echocardiogram and invasive hemodynamic assessment were performed to determine LV contractile function and myocardial oxygen consumption. Serum norepinephrine level was measured before and after SCS. SCS was performed on 2 occasions for 15 minutes, 30 minutes apart (recovery) with 50 Hz frequency (pulse width 0.2 millisecond, 90% of motor threshold at 2 Hz output). Echocardiogram revealed significant decrease in LVEF (33.8 ± 1.8% vs 66.5 ± 1.7%, P < 0.01) after induction of MI and HF. Compared with MI and HF, acute SCS significantly increased LVEF and +dP/dt (all P < 0.05). Withdrawal of SCS during recovery decreased +dP/dt, but not LVEF that increased again with repeated SCS. Myocardial oxygen consumption also significantly decreased during SCS compared with MI and HF (P = 0.006) without any change in serum norepinephrine level (P = 0.9). Speckle tracking imaging showed significant improvement in global and regional circumferential strains over the infarcted mid and apical regions, decreased in time to peak circumferential strain over the lateral and posterior wall after SCS, and the degree of intraventricular dyssynchrony during SCS compared with MI and HF (P < 0.05). CONCLUSIONS: In a porcine model of ischemic HF, acute SCS improved global and regional LV contractile function and intraventricular dyssynchrony, and decreased myocardial oxygen consumption without elevation of norepinephrine level.

Impact of glycemic control on circulating endothelial progenitor cells and arterial stiffness in patients with type 2 diabetes mellitus.

BACKGROUND: Patients with type 2 diabetes mellitus (DM) have increased risk of endothelial dysfunction and arterial stiffness. Levels of circulating endothelial progenitor cells (EPCs) are also reduced in hyperglycemic states. However, the relationships between glycemic control, levels of EPCs and arterial stiffness are unknown. METHODS: We measured circulating EPCs and brachial-ankle pulse wave velocity (baPWV) in 234 patients with type 2 DM and compared them with 121 age- and sex-matched controls. RESULTS: Patients with DM had significantly lower circulating Log CD34/KDR+ and Log CD133/KDR+ EPC counts, and higher Log baPWV compared with controls (all P < 0.05). Among those 120/234 (51%) of DM patients with satisfactory glycemic control (defined by Hemoglobin A1c, HbA1c < 6.5%), they had significantly higher circulating Log CD34/KDR+ and Log CD133/KDR+ EPC counts, and lower Log baPWV compared with patients with poor glycemic control (all P < 0.05). The circulating levels of Log CD34/KDR+ EPC (r = -0.46, P < 0.001) and Log CD133/KDR+ EPC counts (r = -0.45, P < 0.001) were negatively correlated with Log baPWV. Whilst the level of HbA1c positively correlated with Log baPWV (r = 0.20, P < 0.05) and negatively correlated with circulating levels of Log CD34/KDR+ EPC (r = -0.40, P < 0.001) and Log CD133/KDR+ EPC (r = -0.41, P < 0.001). Multivariate analysis revealed that HbA1c, Log CD34/KDR+ and Log CD133/KDR+ EPC counts were independent predictors of Log baPWV (P < 0.05). CONCLUSIONS: In patients with type 2 DM, the level of circulating EPCs and arterial stiffness were closely related to their glycemic control. Furthermore, DM patients with satisfactory glycemic control had higher levels of circulating EPCs and were associated with lower arterial stiffness.

Relationship between ventricular dyssynchrony and T-wave alternans in patients with coronary artery disease.

INTRODUCTION: Coronary artery disease (CAD) is associated with increased dispersion of repolarization and sudden cardiac death. We sought to investigate whether ventricular dyssynchrony is associated with proarrhythmic repolarization dispersion as measured by T-wave alternans (TWA) in patients with CAD. METHODS AND RESULTS: We evaluated 154 patients (67 ± 9 years, 123 men) with documented CAD, who underwent exercise treadmill testing and echocardiographic examination. TWA was analyzed continuously during treadmill testing in all standard precordial leads by time-domain method. Tissue Doppler imaging was performed to measure inter- and intraventricular dyssynchrony. Increased TWA ≥ 60µV was observed in 42 (27%) patients. There was higher prevalence of females (31 vs 16%, P = 0.04) and greater body mass index (25.7 ± 2.6 vs 24.6 ± 3.0 kg/m², P = 0.04) in the TWA ≥ 60µV group of patients than theTWA< 60µV group. The index of interventricular dyssynchrony, Ts-RL, was significantly increased (75.6 ± 37.8 vs 59.9 ± 35.9 ms, P = 0.03) but not intraventricular dyssynchrony (all P > 0.05) in patients with TWA ≥ 60 µV compared with those with TWA < 60 µV. In addition, a weak but significant positive correlation was observed between TWA and Ts-RL (r = 0.25, P = 0.003). Multivariate analysis revealed that only Ts-RL (odds ratio 1.02, 95% confidence interval 1.00­1.03, P = 0.013) was independent predictor for increased TWA. CONCLUSIONS: Our results demonstrated that interventricular dyssynchrony in patients with CAD is associated with increased TWA. This suggests that interventricular dyssynchrony may contribute to proarrhythmic repolarization dispersion.

Effects of right low atrial septal vs. right atrial appendage pacing on atrial mechanical function and dyssynchrony in patients with sinus node dysfunction and paroxysmal atrial fibrillation.

AIMS: To study the effects of right low atrial septum (AS) and right atrial appendage (RAA) pacing on atrial mechanical function and dyssynchrony in patients with sinus node disease (SND) and paroxysmal atrial fibrillation (AF). METHODS AND RESULTS: Detailed echocardiographic examination was performed on 30 patients with SND and paroxysmal AF and a dual-chamber, dual sensing, dual response pacemaker with atrial lead implantation at AS(n= 15) or RAA(n= 15). Peak atrial velocities were recorded by pulsed tissue Doppler spectrum. The timing of atrial contractions (Ta) was measured at the middle of the left atrial (LA) and right atrial (RA) free wall. Intra-[standard deviation (SD) of time of Ta (Ta-SD)] and inter-atrial delay(Ta-RL) was measured as the SD of time interval among LA six segments and time difference between the LA and RA wall, respectively. The baseline clinical statuses were similar between groups. Indexes of LA function, and intra- or inter-atrial dyssynchrony were also similar during intrinsic sinus rhythm in both groups (all P> 0.05). During atrial pacing, LA ejection fraction (52 ± 16 vs. 39 ± 14%, P= 0.029) and LA active emptying fraction (34 ± 7 vs. 23 ± 15%, P= 0.012) were higher in patients with AS than RAA pacing. Atrial velocity was also higher at the RA free wall (14.3 ± 3.1 vs. 10.3 ± 4.4 cm/s, P= 0.009), LA septal (7.5 ± 2.1 vs. 5.2 ± 1.7 cm/s, P= 0.004) and lateral wall (8.6 ± 2.4 vs. 6.3 ± 3.0 cm/s, P= 0.024) during AS compared with RAA pacing. There was no difference in Ts-SD during atrial pacing, nevertheless Ta-RL was significantly prolonged in patients with RAA compared with those with AS pacing (42 ± 36 vs. 27 ± 25 ms, P= 0.011). CONCLUSION: In patients with SND and paroxysmal AF, right low AS pacing significantly improved global and regional atrial mechanical function and synchronized inter-atrial electromechanical contraction compared with RAA pacing.

Hyperthyroidism-induced left ventricular diastolic dysfunction: implication in hyperthyroidism-related heart failure.

BACKGROUND: Heart failure occurs in 6% of hyperthyroid patients. Nonetheless, only half of those with hyperthyroidism-related heart failure have impaired left ventricular (LV) systolic function. Thus, diastolic dysfunction may play an important role in the pathogenesis. METHODS AND RESULTS: We performed serial echocardiographic examinations in 70 consecutive patients with hyperthyroidism (39 ± 2 years, 47 women) to determine their diastolic function and repeated the examinations 6 months after achieving a euthyroid state. All patients had normal LV systolic function, but diastolic dysfunction was detected in 22 cases (mild: 3, moderate: 15 and severe: 4). The prevalence of diastolic dysfunction increased with age from 17·9 % in patients <40 years to 100% in those >60 years. Increasing age was the only independent predictor for diastolic dysfunction in hyperthyroid patients. After achievement of a euthyroid state, most patients (16/22, 72%) had completely normalized diastolic function: 100% of patients <40 years, 33·3 % of those ≥ 60 years. Further analyses revealed significant age-related differences in the cardiovascular response to hyperthyroidism. Among patients <40 years, hyperthyroidism resulted in a marked reduction in total peripheral vascular resistance, increased cardiac output and enhanced diastolic function as determined by E'. No such significant change in total peripheral vascular resistance or cardiac output was observed in hyperthyroid patients ≥ 40 years. In addition, hyperthyroidism was associated with reduced E', signifying diastolic dysfunction in older hyperthyroid patients. CONCLUSION: Hyperthyroidism is associated with diastolic dysfunction, particularly in older patients. It is partly reversible following achievement of a euthyroid state.

Smoking is associated with depletion of circulating endothelial progenitor cells and elevated pulmonary artery systolic pressure in patients with coronary artery disease.

Smoking is associated with depletion of endothelial progenitor cells (EPCs) and may subsequently contribute to the development of vascular dysfunction. The aim of this study was to investigate the relation between circulating EPCs and pulmonary artery systolic pressure (PASP) as determined by flow cytometry and echocardiography in 174 patients (mean age 69 ± 9 years, 95 smokers) with established coronary artery disease. Smokers had significantly lower circulating log CD34/KDR(+) (0.86 ± 0.03 vs 0.96 ± 0.03 × 10⁻³/ml, p = 0.032) and log CD133/KDR(+) (0.68 ± 0.03 vs 0.82 ± 0.03 × 10⁻³/ml, p = 0.002) EPCs and a higher prevalence of elevated PASP >30 mm Hg (52% vs 30%, p = 0.001) than nonsmokers. Smokers with elevated PASP also had significantly lower circulating log CD34/KDR(+) (0.74 ± 0.04 vs 0.88 ± 0.06 × 10⁻³/ml, p <0.001) and log CD133/KDR(+) (0.61 ± 0.04 vs 0.78 ± 0.05 × 10⁻³/ml, p <0.001) EPCs, higher pulmonary vascular resistance, and larger right ventricular dimensions with impaired function (all p values <0.05). Log CD34/KDR(+) and log CD133/KDR(+) EPC counts were significantly and negatively correlated with PASP (r = -0.30, p <0.001, and r = -0.34, p <0.001, respectively) and pulmonary vascular resistance (r = -0.29, p = 0.002, and r = -0.18, p = 0.013, respectively). In conclusion, this study demonstrated that in patients with coronary artery disease, smoking was associated with a reduced number of EPCs and elevated PASP. This suggests that in smokers, depletion of circulating EPCs might be linked to the occurrence of pulmonary vascular dysfunction.

Elevated pulmonary artery systolic pressure in patients with coronary artery disease and left ventricular dyssynchrony.

AIMS: We sought to determine whether inter- or intra-ventricular systolic dyssynchrony contributes to the occurrence of elevated pulmonary artery systolic pressure (PASP) in patients with coronary artery disease (CAD). METHODS AND RESULTS: One hundred and fifty-three consecutive CAD patients with preserved left ventricular ejection fraction (LVEF >40%) were enrolled. Detailed echocardiography was performed to measure PASP, inter-ventricular dyssynchrony (Ts-RL: time difference between lateral and right free wall), and intra-ventricular dyssynchrony (Ts-SD, standard deviation of time to peak systolic velocity of 12 LV segments; Ts-12, maximal difference in Ts between any 2 of 12 LV segments; Ts-6-basal, maximal difference in Ts between any 2 of 6 basal LV segments). Elevated PASP (>35 mmHg) was confirmed in 46 patients who had significantly prolonged intra-ventricular dyssynchrony (Ts-SD: 49.9 ± 19.6 vs.37.9 ± 19.8 ms; Ts-12: 147.9 ± 56.4 vs.110.9 ± 53.9 ms; Ts-6-basal: 114.2 ± 51.9 vs. 85.7 ± 48.5 ms, all P < 0.01) and inter-ventricular dyssynchrony (Ts-RL: 78.7 ± 46.4 vs. 62.7 ± 34.3 ms, P = 0.019) compared with those without elevated PASP. Indexes of intra- and inter-ventricular dyssynchrony and LV filling pressure (E/e') were significantly correlated with PASP. Multivariate analysis showed that left atrial dimension [odds ratio (OR) 4.23, 95% confidence interval (CI) 1.64-10.90], E/e' septal (OR 1.15, 95% CI 1.04-1.27), pulmonary vascular resistance (OR 5.38, 95% CI 1.55-18.74), and Ts-RL (OR 1.02, 95% CI 1.01-1.03) were independent predictors for the occurrence of elevated PASP (all P < 0.05). CONCLUSION: Elevated PASP is common in CAD patients with preserved LVEF and is associated with LV diastolic dysfunction and LV mechanical dyssynchrony.

Beta-blocker in post-myocardial infarct survivors with preserved left ventricular systolic function.

BACKGROUND: Long-term beta-blockade therapy is beneficial in post-myocardial infarct (MI) patients with left ventricular (LV) dysfunction; nevertheless, its benefit in post-MI patients with preserved LV function remains unclear. The objective of this study is to investigate the effects of long-term beta-blockade therapy on the clinical outcomes in post-MI patients with preserved LV function. HYPOTHESIS: The beneficial effects of long-term beta-blockade therapy in post-MI patients with impaired LV function may extend to those with preserved LV function. METHODS: Of 617 consecutive post-MI patients referred for cardiac rehabilitation program, 208 patients (age: 62.7 +/- 0.8 years; male: 76%) with preserved LV function (ejection fraction >or= 50%), negative exercise stress test, and on angiotensin-converting enzyme inhibition were studied. RESULTS: Baseline characteristics were comparable between patients on beta-blocker (n = 154) and not on beta-blocker (n = 54). After a mean follow-up of 58.5 +/- 2.7 months, 14 patients not on beta-blocker (26%) and 14 patients on beta-blocker (9%) died with hazard ratio (HR) of 2.5 (95% confidence interval [CI]: 1.25-6.42, P = 0.01). Likewise, patients not on beta-blocker had a higher incidence of cardiac death (HR: 3.0, 95% CI: 1.07-12.10, P = 0.04), and non-sudden cardiac death (HR: 10.1, 95% CI: 1.82-89.65, P = 0.01), but not sudden cardiac death compared with patients on beta-blocker (HR: 1.6, 95% CI: 0.34-7.61, P = 0.54). A Cox regression analysis revealed that only advanced age (>or=75 years; HR: 2.55, 95% CI: 1.18-5.49, P = 0.02) and the absence of beta-blocker (HR: 2.41, 95% CI: 1.14-5.09, P = 0.02) were independent predictors for mortality. CONCLUSION: beta-blocker use was associated with a decrease in overall mortality and cardiac death in post-MI patients with preserved LV function.