Stephen W.L. Lee

New‐Onset Heart Failure After Permanent Right Ventricular Apical Pacing in Patients with Acquired High‐Grade Atrioventricular Block and Normal Left Ventricular Function

Introduction: Emerging data have suggested that right ventricular (RV) apical pacing results in progressive left ventricular (LV) dysfunction and contributes to the development of heart failure (HF). This study aimed to investigate the prevalence and clinical predictors for the development of new‐onset HF after long‐term RV apical pacing in patients with acquired atrioventricular (AV) block who require permanent pacing.

Vitamin D Deficiency Is Associated with Depletion of Circulating Endothelial Progenitor Cells and Endothelial Dysfunction in Patients with Type 2 Diabetes

CONTEXT Vitamin D (Vit-D) deficiency is associated with type 2 diabetes mellitus (DM) and endothelial dysfunction. The relationship of Vit-D deficiency with circulating endothelial progenitor cells and endothelial dysfunction in type 2 DM patients nonetheless remains unclear. OBJECTIVE We aimed to investigate the cross-sectional association of Vit-D status with brachial flow-mediated dilation (FMD) and circulating endothelial progenitor cell (EPC) numbers in type 2 DM patients. DESIGN, SETTING, AND PARTICIPANTS We conducted a cross-sectional study of 280 patients (59% male, aged 68 ± 10 yr) with type 2 DM recruited in outpatient clinics during the winter period. MAIN OUTCOME MEASURE We measured serum 25-hydroxyvitamin D [25(OH)D] by an ELISA kit, circulating CD34+/kinase insert domain-containing receptor (KDR)+ and CD133+/KDR+ EPCs by flow cytometry and brachial artery FMD by vascular ultrasound, respectively. RESULTS The mean serum 25(OH)D concentration was 25.00 ± 9.17 ng/ml, and 34.3% of patients had Vit-D deficiency [25(OH)D < 20 ng/ml]. Serum 25(OH)D concentration had a significant correlation with hemoglobin A1c level [B = -0.018, 95% confidence interval (CI) -0.035 to -0.002, P = 0.032]. Patients with Vit-D deficiency status had significantly lower brachial FMD (mean difference -1.43%, 95% CI -2.31 to -0.55, P = 0.001) and CD133+/KDR+EPC counts (mean difference -0.12%, 95% CI -0.21 to -0.019, P = 0.022) than those with sufficient Vit-D status after adjustment for age, sex, and cardiovascular risk factors, including hemoglobin A1c levels. CONCLUSIONS Our results demonstrate that serum 25(OH)D status was significantly associated with brachial artery FMD and circulating CD133+/KDR+EPCs. This suggests that Vit-D deficiency might contribute to depletion of EPCs and endothelial dysfunction in patients with type 2 DM.

Optical coherence tomography imaging during percutaneous coronary intervention impacts physician decision-making: ILUMIEN I study

Aims ILUMIEN I is the largest prospective, non-randomized, observational study of percutaneous coronary intervention (PCI) procedural practice in patients undergoing intra-procedural pre- and post-PCI fractional flow reserve (FFR) and optical coherence tomography (OCT). We report on the impact of OCT on physician decision-making and the association with post-PCI FFR values and early clinical events. Methods and results Optical coherence tomography and documentary FFR were performed pre- and post-PCI in 418 patients (with 467 stenoses) with stable or unstable angina or NSTEMI. Based on pre-PCI OCT, the procedure was altered in 55% of patients (57% of all stenoses) by selecting different stent lengths (shorter in 25%, longer in 43%). After clinically satisfactory stent implantation using angiographic guidance, post-PCI FFR and OCT were repeated. Optical coherence tomography abnormalities deemed unsatisfactory by the implanting physician were identified: 14.5% malapposition, 7.6% under-expansion, 2.7% edge dissection and prompted further stent optimization based on OCT in 25% of patients (27% of all stenoses) using additional in-stent post-dilatation (81%, 101/124) or placement of 20 new stents (12%). Optimization subgroups were identified post hoc: stent placement without reaction to OCT findings (n = 137), change in PCI planning by pre-PCI OCT (n = 165), post-PCI optimization based on post-PCI OCT (n = 41), change in PCI planning, and post-PCI optimization based on OCT (n = 65). Post-PCI FFR values were significantly different (P = 0.003) between optimization groups (lower in cases with pre- and post-PCI reaction to OCT) but no longer different after post-PCI stent optimization. MACE events at 30 days were low: death 0.25%, MI 7.7%, repeat PCI 1.7%, and stent thrombosis 0.25%. Conclusion Physician decision-making was affected by OCT imaging prior to PCI in 57% and post-PCI in 27% of all cases. ClinicalTrials.gov Identifier NCT01663896, Observational Study of Optical Coherence Tomography (OCT) in Patients Undergoing Fractional Flow Reserve (FFR) and Percutaneous Coronary Intervention (ILUMIEN I).

Reversal of mitochondrial dysfunction by coenzyme Q10 supplement improves endothelial function in patients with ischaemic left ventricular systolic dysfunction: A randomized controlled trial

AIMS Coronary artery disease (CAD) is associated with endothelial dysfunction and mitochondrial dysfunction (MD). The aim of this study was to investigate whether co-enzyme Q10 (CoQ) supplementation, which is an obligatory coenzyme in the mitochondrial respiratory transport chain, can reverse MD and improve endothelial function in patients with ischaemic left ventricular systolic dysfunction (LVSD). METHODS AND RESULTS We performed a randomized, double-blind, placebo-controlled trial to determine the effects of CoQ supplement (300 mg/day, n=28) vs. placebo (controls, n=28) for 8 weeks on brachial flow-mediated dilation (FMD) in patients with ischaemic LVSD(left ventricular ejection fraction <45%). Mitochondrial function was determined by plasma lactate/pyruvate ratio (LP ratio). After 8 weeks, CoQ-treated patients had significant increases in plasma CoQ concentration (treatment effect 2.20 μg/mL, P<0.001) and FMD (treatment effect 1.51%, P=0.03); and decrease in LP ratio (treatment effect -2.46, P=0.03) compared with controls. However, CoQ treatment did not alter nitroglycerin-mediated dilation, blood pressure, blood levels of fasting glucose, haemoglobin A1c, lipid profile, high-sensitivity C-reactive protein and oxidative stress as determined by serum superoxide dismutase and 8-isoprostane (all P>0.05). Furthermore, the reduction in LP ratio significantly correlated with improvement in FMD (r=-0.29, P=0.047). CONCLUSION In patients with ischaemic LVSD, 8 weeks supplement of CoQ improved mitochondrial function and FMD; and the improvement of FMD correlated with the change in mitochondrial function, suggesting that CoQ improved endothelial function via reversal of mitochondrial dysfunction in patients with ischaemic LVSD.

Habitual physical activity is associated with endothelial function and endothelial progenitor cells in patients with stable coronary artery disease

Background Exercise training reduces mortality in patients with coronary artery disease (CAD); however, the impact of habitual physical activity level (PAL) on vascular endothelial function and circulating endothelial progenitor cells (EPCs) remain unknown. Methods We assessed habitual PAL using a validated International Physical Activity Questionnaire in 116 patients (67.8 ± 9.5 years; 81% male) with stable CAD and preserved left ventricular ejection fraction ≥ 45%. The number of circulating CD34/KDR+ and CD133/KDR+ EPCs was determined by flow cytometry, and brachial artery flow-mediated dilation (FMD) was measured. Results The mean PAL of CAD patients with 1644 MET min/week (where MET is metabolic equivalents). With higher habitual PAL tertiles, there were significant linear trends of increased FMD (P = 0.001) and CD133/KDR+ EPCs (P = 0.03), but not of CD34/KDR+ EPCs. Patients with the highest tertile of PAL were associated with an absolute increase of 1.89% in FMD (relative increase 68%, P = 0.003) and 0.12% in CD133/KDR+ EPCs (relative increase 44%, P = 0.01) compared with those in the lowest tertile of PAL, after adjusting for age, sex, presence of hypertension, diabetes mellitus, hypercholesterolemia, smoking, and the use of medications including statins. However, neither CD34/KDR+ nor CD133/KDR+ EPCs significantly correlated with FMD. Conclusion This study showed that higher habitual PAL in patients with CAD was associated with higher FMD and EPC count. Nonetheless, FMD only significantly correlated with increased PAL, but not EPC, suggesting that increased physical activity improves endothelial function through mechanisms other than increasing EPC count.

Subclinical left ventricular dysfunction revealed by circumferential 2D strain imaging in patients with coronary artery disease and fragmented QRS complex

BACKGROUND Fragmented QRS (fQRS) complexes on a routine 12-lead electrocardiogram were associated with adverse cardiac events, including sudden death in patients with coronary artery disease (CAD). OBJECTIVE To investigate the relationship between the fQRS complex and global and regional left ventricular (LV) functions in patients with CAD. METHODS The study consisted of 176 patients (68 ± 9 years; 145 [82%] men) with CAD with narrow QRS duration and preserved LV ejection fraction (>45%). All patients underwent detailed 2-dimensional speckle-tracking echocardiography to determine global and segmental (basal, middle, and apical) LV strains and strain rates and were prospectively followed-up in the outpatient clinic. RESULTS Fifty-five patients (31%) had fQRS complexes. Global, middle, and apical LV longitudinal, radial, and circumferential strains and strain rates were significantly lower in the fQRS group than in the non-fQRS group (all P <.05). Multivariate logistic regression analysis revealed that the fQRS complex was associated with decreased global circumferential strain (odds ratio 1.19; 95% confidence interval 1.06-1.33; P = .003) and multivessel disease (odds ratio 3.69; 95% confidence interval 1.35-10.08; P = .011). Kaplan-Meier analysis revealed that event-free survival for cardiac events was significantly lower in the fQRS group than in the non-fQRS group (P = .036). CONCLUSIONS Our results demonstrated that the fQRS complex in patients with CAD with preserved LV ejection fraction was associated with subclinical global and regional LV dysfunctions as detected by 2-dimensional speckle-tracking imaging, and the results also predicted adverse cardiac events.

Very late stent thrombosis due to DES fracture: description of a case and review of potential causes.

Stent fracture and subsequent stent thrombosis are known complications after stent implantation, especially in stents with closed cell design like the first generation sirolimus drug eluting stents (DES). Late stent thrombosis is very rarely encountered in our patient population, majority Chinese. We report a case of non‐ST elevation myocardial infarction as a result of very late stent thrombosis (three years after implantation) due to stent fracture at the site of overlap of two first generation sirolimus DES. There were initial difficulties in restoring coronary flow by conventional reperfusion therapies but a successful outcome after implantation of an endothelial progenitor cell capture stent, with no further recurrence of ischemic event after 12 months. An attempt was made to analyze all existing factors present and contributing to the stent fracture and stent thrombosis in this case, as reported in the literature.

Catastrophic health expenditure on acute coronary events in Asia: a prospective study.

Abstract Objective To estimate out-of-pocket costs and the incidence of catastrophic health expenditure in people admitted to hospital with acute coronary syndromes in Asia. Methods Participants were enrolled between June 2011 and May 2012 into this observational study in China, India, Malaysia, Republic of Korea, Singapore, Thailand and Viet Nam. Sites were required to enrol a minimum of 10 consecutive participants who had been hospitalized for an acute coronary syndrome. Catastrophic health expenditure was defined as out-of-pocket costs of initial hospitalization > 30% of annual baseline household income, and it was assessed six weeks after discharge. We assessed associations between health expenditure and age, sex, diagnosis of the index coronary event and health insurance status of the participant, using logistic regression models. Findings Of 12 922 participants, 9370 (73%) had complete data on expenditure. The mean out-of-pocket cost was 3237 United States dollars. Catastrophic health expenditure was reported by 66% (1984/3007) of those without insurance versus 52% (3296/6366) of those with health insurance (P < 0.05). The occurrence of catastrophic expenditure ranged from 80% (1055/1327) in uninsured and 56% (3212/5692) of insured participants in China, to 0% (0/41) in Malaysia. Conclusion Large variation exists across Asia in catastrophic health expenditure resulting from hospitalization for acute coronary syndromes. While insurance offers some protection, substantial numbers of people with health insurance still incur financial catastrophe.

Evaluation of Early Healing Profile and Neointimal Transformation Over 24 Months Using Longitudinal Sequential Optical Coherence Tomography Assessments and 3-Year Clinical Results of the New Dual-Therapy Endothelial Progenitor Cell Capturing Sirolimus-Eluting Combo Stent: The EGO-Combo Study.

Background—Current monotherapy drug-eluting stents are associated with impaired healing, neoatherosclerosis, and late stent thrombosis. The healing profile and neointimal transformation of the first dual-therapy endothelial progenitor cell–capturing sirolimus-eluting stent are unknown. Methods and Results—In this prospective, single-center study, 61 patients treated with the Combo stent had optical coherence tomography at baseline, early follow-up (4 monthly groups in a 1:2:2:1 ratio from 2 to 5 months), 9 months, and 24 months. Optical coherence tomography early strut coverage increased from 77.1% to 92.5% to 92.7% to 94.9% between 2 and 5 months. At 9 months, the major adverse cardiac event rate was 1.64%, and angiographic in-stent late loss was 0.24 mm (0.08–0.40). The 36-month major adverse cardiac event rate was 3.3%. From 9 to 24 months, neointimal regression was confirmed by optical coherence tomography: neointimal thickness (median [first quartile and third quartile]), 0.14 mm (0.08 and 0.21) versus 0.12 mm (0.07 and 0.19), P<0.001; neointimal volume, 29.9 mm3 (22.1 and 43.2) versus 26.2 mm3 (19.6 and 35.8), P=0.003; and percent neointimal volume, 17.8% (12.2 and 21.2) versus 15.7% (11.2 and 19.4), P=0.01. No definite or probable late stent thrombosis was recorded. Conclusions—With additional endothelial progenitor cell–capturing technology, the Combo stent exhibits a unique late neointimal regression (from 9 to 24 months) that has not been reported in any drug-eluting stents, translating into good 36-month clinical results with minimal restenosis and no late stent thrombosis. This is the first study testing the concept of using a longitudinal sequential optical coherence tomography protocol to continuously document early healing profile and late neointimal transformation, predicting long-term outcomes of a new novel stent platform. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01274234, NCT01756807, and NCT02263313.

Prediction of aortic augmentation index using radial pulse transmission-wave analysis

Objective Current arterial transfer functions have low capability in predicting aortic augmentation index (AIx) from radial pulse contour (RPC), because of the difficulty in accurately identifying the merging point (inflection point) in the derived aortic pulse contour (APC). We hypothesize that the formation time between each characteristic wave in APC is about one-third of ejection duration (ED/3). We sought to assess the accuracy of ED/3 in identifying the merging point in APC as compared to the conventional differential method. In addition, we sought to derive the AIx from RPC based on an arterial transfer function and the ED/3 method. Methods APC and RPC sequences were measured digitally and simultaneously in 60 subjects (37 males; aged 60 ± 10 years). An ensemble-averaged RPC-to-APC transfer function was determined from 30 randomly selected subjects and was used to derive APC sequences in the 30 additional subjects. The accuracy of AIx predicted from RPC was determined. Results In patients with a clearly identifiable merging point in APC, the ED/3 method identified the merging point of measured APC within 1.97 ± 0.60 ms of that identified by the conventional differential method, with identical AIx. The AIx and merging point of derived APC using the ED/3 method were also within 0.22 ± 1.01% and 1.81 ± 1.64 ms, respectively, of those of the measured APC using the conventional differential method. The accuracy of the predicted AIx was independent of age, sex, body-mass index and presence of hypertension. Conclusion In a quiet resting state, the ED/3 is an alternative method for identifying the merging point in APC. In conjunction with transfer–function technique, AIx can be derived accurately from RPC.