Shun-Ling Kong

Left Ventricular Reverse Remodeling but Not Clinical Improvement Predicts Long-Term Survival After Cardiac Resynchronization Therapy

Background—In patients with severe heart failure and dilated cardiomyopathy, cardiac resynchronization therapy (CRT) improves left ventricular (LV) systolic function associated with LV reverse remodeling and favorable 1-year survival. However, it is unknown whether LV reverse remodeling translates into a better long-term prognosis and what extent of reverse remodeling is clinically relevant, which were investigated in this study. Methods and Results—Patients (n=141) with advanced heart failure (mean±SD age, 64±11 years; 73% men) who received CRT were followed up for a mean (±SD) of 695±491 days. The extent of reduction in LV end-systolic volume (LVESV) at 3 to 6 months relative to baseline was examined for its predictive value on long-term clinical outcome. The cutoff value for LV reverse remodeling in predicting mortality was derived from the receiver operating characteristic curve. Then the relation between potential predictors of mortality and heart failure hospitalizations were compared by Kaplan-Meier survival analysis, followed by Cox regression analysis. There were 22 (15.6%) deaths, mostly due to heart failure or sudden cardiac death. The receiver operating characteristic curve found that a reduction in LVESV of ≥9.5% had a sensitivity of 70% and specificity of 70% in predicting all-cause mortality and of 87% and 69%, respectively, for cardiovascular mortality. With this cutoff value, there were 87 (61.7%) responders to reverse remodeling. In Kaplan-Meier survival analysis, responders had significantly lower all-cause morality (6.9% versus 30.6%, log-rank &khgr;2=13.26, P=0.0003), cardiovascular mortality (2.3% versus 24.1%, log-rank &khgr;2=17.1, P<0.0001), and heart failure events (11.5% versus 33.3%, log-rank &khgr;2=8.71, P=0.0032) than nonresponders. In the Cox regression analysis model, the change in LVESV was the single most important predictor of all-cause (&bgr;=1.048, 95% confidence interval=1.019 to 1.078, P=0.001) and cardiovascular (&bgr;=1.072, 95% confidence interval=1.033 to 1.112, P<0.001) mortality. Clinical parameters were unable to predict any outcome event. Conclusions—A reduction in LVESV of 10% signifies clinically relevant reverse remodeling, which is a strong predictor of lower long-term mortality and heart failure events. This study suggests that assessing volumetric changes after an intervention in patients with heart failure provides information predictive of natural history outcomes.

Intrathoracic Impedance Monitoring in Patients With Heart Failure. Correlation With Fluid Status and Feasibility of Early Warning Preceding Hospitalization

Background—Patients with heart failure are frequently hospitalized for fluid overload. A reliable method for chronic monitoring of fluid status is therefore desirable. We evaluated an implantable system capable of measuring intrathoracic impedance to identify potential fluid overload before heart failure hospitalization and to determine the correlation between intrathoracic impedance and standard measures of fluid status during hospitalization. Methods and Results—Thirty-three patients with NYHA class III and IV heart failure were implanted with a special pacemaker in the left pectoral region and a defibrillation lead in the right ventricle. Intrathoracic impedance was regularly measured and recorded between the lead and the pacemaker case. During hospitalizations, pulmonary capillary wedge pressure and fluid status were monitored. Ten patients were hospitalized for fluid overload 25 times over 20.7±8.4 months. Intrathoracic impedance decreased before each admission by an average of 12.3±5.3% (P<0.001) over an average of 18.3±10.1 days. Impedance reduction began 15.3±10.6 days (P<0.001) before the onset of worsening symptoms. There was an inverse correlation between intrathoracic impedance and pulmonary capillary wedge pressure (r=−0.61, P<0.001) and between intrathoracic impedance and net fluid loss (r=−0.70, P<0.001) during hospitalization. Automated detection of impedance decreases was 76.9% sensitive in detecting hospitalization for fluid overload, with 1.5 false-positive (threshold crossing without hospitalization) detections per patient-year of follow-up. Conclusions—Intrathoracic impedance is inversely correlated with pulmonary capillary wedge pressure and fluid balance and decreased before the onset of patient symptoms and before hospital admission for fluid overload. Regular monitoring of impedance may provide early warning of impending decompensation and diagnostic information for titration of medication.

Comparison of Efficacy of Reverse Remodeling and Clinical Improvement for Relatively Narrow and Wide QRS Complexes After Cardiac Resynchronization Therapy for Heart Failure

Introduction: Cardiac resynchronization therapy (CRT) has been shown to reverse left ventricular (LV) remodeling and improve symptoms in heart failure patients with wide QRS complexes; however, its role in patients with mildly prolonged QRS complexes is unclear. This study investigated if CRT benefited patients with mildly prolonged QRS complexes >120 to 150 ms and explored if the severity of systolic asynchrony determined such a response.

Comparison of acute changes in left ventricular volume, systolic and diastolic functions, and intraventricular synchronicity after biventricular and right ventricular pacing for heart failure

BACKGROUND Biventricular pacing (BiV) therapy has recently been shown to improve systolic function and cause reverse remodeling in patients with advanced heart failure with electromechanical delay. In these patients, the benefit of right ventricular (RV)-based pacing was controversial. We compared the acute changes in systolic and diastolic function, left ventricular (LV) volume, and intraventricular synchronicity in BiV pacing, RV pacing, and without pacing (No) by means of echocardiography and tissue Doppler imaging (TDI). METHODS TDI was performed in 33 patients with heart failure after undergoing pacemaker implantation, when the device was randomized to BiV, RV, and no pacing modes. RESULTS Systolic function was only improved during BiV pacing, but not during RV pacing. This included ejection fraction (No vs RV vs BiV = 24% +/- 12% vs 25% +/- 10% vs 30% +/- 14%, P =.02 vs No), +dp/dt (P =.01), myocardial performance index (P =.01), and isovolumic contraction time (P =.03). Mitral regurgitation was only reduced during BiV pacing (P =.02). LV early diastolic function was depressed in both RV and BiV pacing, as detected by transmitral flow (97 +/- 34 vs 80 +/- 34 vs 82 +/- 32 cm/s, both P < or =.005) and TDI (mean myocardial early diastolic velocity of 6 basal segments, 3.3 +/- 1.7 vs 2.6 +/- 1.0 vs 2.6 +/- 1.0 cm/s, both P =.01). The LV end-diastolic (187 +/- 86 vs 177 +/- 84 vs 166 +/- 79, P =.003) and end-systolic (146 +/- 77 vs 138 +/- 79 vs 122 +/- 69, P =.003) volumes were only decreased during BiV pacing. For systolic synchronicity, a significant delay in peak systolic contraction in the lateral over the septal wall (171 +/- 37 vs 217 +/- 46 ms, P =.004) was revealed by TDI when there was no pacing. This was abolished by BiV pacing, in which septal contraction was delayed (195 +/- 38 vs 201 +/- 53 ms, P = not significant). However, RV pacing restored the lateral wall delay, and systolic asynchrony reappeared (190 +/- 40 vs 227 +/- 56 ms, P =.01). Diastolic asynchrony between the septal and lateral walls was not evident in these patients and was not affected by either pacing mode. CONCLUSION Only BiV pacing, but not RV pacing, improves systolic function, and reduces mitral regurgitation and LV volumes in patients with heart failure and electromechanical delay. This is attributed to the improvement of systolic synchronicity. Diastolic synchronicity was unaffected, whereas early diastolic function could be jeopardized, by either pacing mode.

Comparison of intensive and low-dose atorvastatin therapy in the reduction of carotid intimal–medial thickness in patients with coronary heart disease

Background: Intensive statin therapy has been shown to improve prognosis in patients with coronary heart disease (CHD). It is unknown whether such benefit is mediated through the reduction of atherosclerotic plaque burden. Aim: To examine the efficacy of high-dose atorvastatin in the reduction of carotid intimal–medial thickness (IMT) and inflammatory markers in patients with CHD. Design: Randomised trial. Setting: Single centre. Patients: 112 patients with angiographic evidence of CHD. Interventions: A high dose (80 mg daily) or low dose (10 mg daily) of atorvastatin was given for 26 weeks. Main outcome measures: Carotid IMT, C-reactive protein (CRP) and proinflammatory cytokine levels were assessed before and after therapy. Results: The carotid IMT was reduced significantly in the high-dose group (left: mean (SD), 1.24 (0.48) vs 1.15 (0.35) mm, p = 0.02; right: 1.12 (0.41) vs 1.01 (0.26) mm, p = 0.01), but was unchanged in the low-dose group (left: 1.25 (0.55) vs 1.20 (0.51) mm, p = NS; right: 1.18 (0.54) vs 1.15 (0.41) mm, p = NS). The CRP levels were reduced only in the high-dose group (from 3.92 (6.59) to 1.35 (1.83) mg/l, p = 0.01), but not in the low-dose group (from 2.25 (1.84) to 3.36 (6.15) mg/l, p = NS). A modest correlation was observed between the changes in carotid IMT and CRP (r = 0.21, p = 0.03). Conclusions: In patients with CHD, intensive atorvastatin therapy results in regression of carotid atherosclerotic disease, which is associated with reduction in CRP levels. On the other hand, a low-dose regimen only prevents progression of the disease.

MODELING THE MULTIWAVELENGTH LIGHT CURVES OF PSR B1259-63/LS 2883. II. THE EFFECTS OF ANISOTROPIC PULSAR WIND AND DOPPLER BOOSTING

PSR B1259-63/LS 2883 is a binary system in which a 48 ms pulsar orbits around a Be star in a high eccentric orbit with a long orbital period of about 3.4 yr. It is special for having asymmetric two-peak profiles in both the X-ray and TeV light curves. Recently, an unexpected GeV flare has been detected by the Fermi gamma-ray observatory several weeks after the last periastron passage. In this paper, we show that this observed GeV flare could be produced by the Doppler-boosted synchrotron emission in the bow-shock tail. An anisotropic pulsar wind model, which mainly affects the energy flux injection into the termination shock in a different orbital phase, is also used in this paper, and we find that the anisotropy in the pulsar wind can play a significant role in producing the asymmetric two-peak profiles in both X-ray and TeV light curves. The X-ray and TeV photons before periastron are mainly produced by the shocked electrons around the shock apex, and the light curves after periastron are contributed by the emission from the shock apex and the shock tail together, which result in asymmetric two-peak light curves.

Variation of microphysics in wind bubbles: an alternative mechanism for explaining the rebrightenings in Gamma-ray burst afterglows

Conventionally, long Gamma-ray bursts (GRBs) are thought to be caused by the core collapses of massive stars. During the lifetime of a massive star, a stellar wind bubble environment should be produced. Furthermore, the microphysics shock parameters may vary along with the evolution of the fireball. Here, we investigate the variation of the microphysics shock parameters under the condition of wind bubble environment, and allow the microphysics shock parameters to be discontinuous at shocks in the ambient medium. It is found that our model can acceptably reproduce the rebrightenings observed in GRB afterglows, at least in some cases. The effects of various model parameters on rebrightenings are investigated. The rebrightenings observed in both the R-band and X-ray afterglow light curves of GRB 060206, GRB 070311 and GRB 071010A are reproduced in this model.

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.

The OCT-ORION Study: A Randomized Optical Coherence Tomography Study Comparing Resolute Integrity to Biomatrix Drug-Eluting Stent on the Degree of Early Stent Healing and Late Lumen Loss

Background— Durable polymers used in drug-eluting stents are considered a potential cause of hypersensitivity inflammatory response adversely affecting stent healing. Using a sequential follow-up with optical coherence tomography, we compared the differences in healing profiles of 2 drug-eluting stents with a biodegradable or durable polymer. Methods and Results— Sixty patients with multivessel disease were prospectively enrolled to receive both study stents, which were randomly assigned to 2 individual vessels, a Resolute Integrity zotarolimus-eluting stent with a durable BioLinx polymer and a BioMatrix NeoFlex Biolimus A9–eluting stent with a biodegradable polylactic acid polymer. Optical coherence tomography was performed at baseline, then in 5 randomly assigned monthly groups at 2 to 6 months, and at 9 months in all patients. The primary end point was the difference in optical coherence tomography strut coverage at 9 months. Key secondary end points included angiographic late lumen loss and composite major adverse cardiac events (cardiac death, myocardial infarction, target lesion revascularization, and definite or probable stent thrombosis) at 9 months. Resolute Integrity zotarolimus-eluting stent showed significantly better strut coverage than BioMatrix NeoFlex Biolimus A9–eluting stent at 2 to 6 months (P<0.001) and less variance of percent coverage at 9 months, 99.7% (interquartile range, 99.1–100) versus 99.6% (interquartile range, 96.8–99.9; difference, 0.10; 95% confidence interval, 0.00–1.05; P<0.001). No significant difference was observed in major adverse cardiac events or angiographic end points. Conclusions— Despite having a durable polymer, Resolute Integrity zotarolimus-eluting stent exhibited better strut coverage than BioMatrix NeoFlex Biolimus A9–eluting stent having a biodegradable polymer; both showed similar antiproliferative efficacy. This novel, longitudinal, sequential optical coherence tomography protocol using each patient as own control could achieve conclusive results in small sample size. Clinical Trial Registration— URL: https://www.clinicaltrials.gov. Unique identifier: NCT01742507.

Modeling afterglow rebrightenings by evolving the microphysics in the termination shock

Conventionally, long GRBs are thought to be caused by the core collapses of massive stars. During the lifetime of a massive star, a termination shock environment should be produced. Furthermore, the microphysics shock parameters may vary along with the evolution of the fireball. Our numerical simulations indicate that adding the evolution of the microphysics shock parameters in the termination shock can acceptably reproduce the rebrightenings in both the R‐band and X‐ray afterglow light curves of GRBs, for example GRB 060206, GRB 070311 and GRB 071010A.