Taek Geun Kwon

Prognostic Value of Flow‐Mediated Vasodilation in Brachial Artery and Fingertip Artery for Cardiovascular Events: A Systematic Review and Meta‐Analysis

Background Endothelial dysfunction plays a pivotal role in cardiovascular disease progression, and is associated with adverse events. The purpose of this systematic review and meta‐analysis was to investigate the prognostic magnitude of noninvasive peripheral endothelial function tests, brachial artery flow‐mediated dilation (FMD), and reactive hyperemia–‐peripheral arterial tonometry (RH‐PAT) for future cardiovascular events. Methods and Results Databases of MEDLINE, EMBASE, and the Cochrane Library were systematically searched. Clinical studies reporting the predictive value of FMD or RH‐PAT for cardiovascular events were identified. Two authors selected studies and extracted data independently. Pooled effects were calculated as risk ratio (RR) for continuous value of FMD and natural logarithm of RH‐PAT index (Ln_RHI) using random‐effects models. Thirty‐five FMD studies of 17 280 participants and 6 RH‐PAT studies of 1602 participants were included in the meta‐analysis. Both endothelial function tests significantly predicted cardiovascular events (adjusted relative risk [95% CI]: 1% increase in FMD 0.88 [0.84–0.91], P<0.001, 0.1 increase in Ln_RHI 0.79 [0.71–0.87], P<0.001). There was significant heterogeneity in the magnitude of the association across studies. The magnitude of the prognostic value in cardiovascular disease subjects was comparable between these 2 methods; a 1 SD worsening in endothelial function was associated with doubled cardiovascular risk. Conclusions Noninvasive peripheral endothelial function tests, FMD and RH‐PAT, significantly predicted cardiovascular events, with similar prognostic magnitude. Further research is required to determine whether the prognostic values of these 2 methods are independent of each other and whether an endothelial function–guided strategy can provide benefit in improving cardiovascular outcomes.

Coronary Endothelial Dysfunction Is Associated With Inflammation and Vasa Vasorum Proliferation in Patients With Early Atherosclerosis

Objective—Endothelial dysfunction is an early manifestation of atherosclerosis. Inflammation and vasa vasorum play a pivotal role in the pathophysiology of plaque initiation, development, and complications. Optical coherence tomography allows high-resolution imaging of tissue microstructure. Therefore, the aim of this study was to test the hypothesis that segments with endothelial dysfunction show macrophages and vasa vasorum in patients with early coronary artery disease. Approach and Results—Optical coherence tomography images were obtained from 40 patients with mild coronary atherosclerosis who underwent coronary endothelial function assessment. Optical coherence tomography findings, including macrophages and microchannels, were evaluated in 76 coronary segments corresponding to those in endothelial response to acetylcholine. Coronary artery diameter change in response to acetylcholine was more severe in segments showing macrophages (−17.7±14.7% versus −6.3±13.9%; P<0.01) and microchannels (−15.9±15.9% versus −6.4±13.5%; P<0.01) than those without. There were increasing trends of the prevalence of macrophages and microchannels with endothelial dysfunction as stratified by quartiles of coronary artery diameter change (P<0.01 and P=0.02 for trend, respectively). In particular, segments with both macrophages and microchannels (n=12) tended to have worse endothelial function than those with macrophages alone (n=15) and microchannels alone (n=15; −22.1±14.6% versus −10.9±15.6% and −10.9±15.6%; P=0.07 and P=0.06, respectively). Conclusions—Epicardial endothelial dysfunction was associated with optical coherence tomography –identified macrophages and microchannels in mild coronary atherosclerosis. The current study further supports the role of inflammation and vasa vasorum proliferation in the early stage of coronary atherosclerosis.

Treating coronary disease and the impact of endothelial dysfunction.

Ischemic heart disease is the leading cause of morbidity and mortality throughout the world. Many clinical trials have suggested that lifestyle and pharmacologic interventions are effective in attenuating atherosclerotic disease progression and events development. However, an individualized approach with careful consideration to comprehensive vascular health is necessary to perform successful intervention strategies. Endothelial dysfunction plays a pivotal role in the early stage of atherosclerosis and is also associated with plaque progression and occurrence of atherosclerotic complications. The assessment of endothelial function provides us with important information about individual patient risk, progress and vulnerability of disease, and guidance of therapy. Thus, the application of endothelial function assessment might enable clinicians to innovate ideal individualized medicine. In this review, we summarize the current knowledge on the impact of pharmacological therapies for atherosclerotic cardiovascular disease on endothelial dysfunction, and argue for the utility of non-invasive assessment of endothelial function aiming at individualized medicine.

Secondary Prevention Strategy of Cardiovascular Disease Using Endothelial Function Testing

Over the past decades, secondary prevention of cardiovascular (CV) disease has improved and considerably reduced mortality rates. However, there remains a high-rate of new or recurrent CV events in those with established atherosclerotic vascular diseases. Although most of the prevailing therapies target the conventional risk factors, there is notable interindividual heterogeneity in adaptation to risk factors and response to therapies, which affects efficacy. It is desirable to have a methodology for directly assessing the functional significance of atherogenesis, and for managing individual patients based on their comprehensive vascular health. Endothelial function plays a pivotal role in all stages of atherosclerosis, from initiation to atherothrombotic complication. Endothelial function reflects the integrated effect of all the atherogenic and atheroprotective factors present in an individual, and is therefore regarded as an index of active disease process and a significant risk factor for future CV events. Moreover, improvement in endothelial function is associated with decreased risk of CV events, even in the secondary prevention setting. The introduction of endothelial function assessment into clinical practice may trigger the development of a more tailored and personalized medicine and improve patient outcomes. In this review, we summarize current knowledge on the contribution of endothelial dysfunction to atherosclerotic CV disease in the secondary prevention setting. Finally, we focus on the potential of an endothelial function-guided management strategy in secondary prevention.

Predictive value of endothelial function by noninvasive peripheral arterial tonometry for coronary artery disease.

BackgroundEndothelial dysfunction is a key step in the initiation and progression of atherosclerosis and subsequent cardiovascular complications. We examined whether peripheral endothelial function, as assessed by fingertip reactive hyperemia-peripheral arterial tonometry (RH-PAT), can provide additional clinical value to traditional risk factors for cardiovascular diseases in predicting coronary artery disease (CAD). MethodsWe included 118 stable patients who were referred for coronary angiography for chest pain evaluation or due to abnormal stress test results. A natural logarithmic value of the RH-PAT index (Ln_RHI) was obtained before cardiac catheterization by an independent operator. Significant CAD was defined as luminal stenosis of at least 70% (≥50% at left main) and/or fractional flow reserve of up to 0.80 in one or more major coronary arteries or their major branches. ResultsLevels of Ln_RHI were significantly lower in patients with CAD (n=60) compared with patients without CAD (n=58; 0.69±0.29 vs. 0.88±0.27, P<0.001). Ln_RHI was significantly associated with CAD independent from traditional risk factors (odds ratio for a 0.1 decrease in Ln_RHI=1.25, 95% confidence interval: 1.04–1.52, P=0.01). The net reclassification index was improved when Ln_RHI was added to traditional risk factors (0.62, 95% confidence interval: 0.27–0.97, P=0.001). ConclusionPeripheral endothelial function, as assessed by RH-PAT, improved risk stratification when added to traditional risk factors. RH-PAT is potentially useful for identifying patients at high risk for CAD.

Relation between fractional flow reserve value of coronary lesions with deferred revascularization and cardiovascular outcomes in non-diabetic and diabetic patients

BACKGROUND FFR of deferred PCI lesions can predict future cardiovascular events. However, the prognostic utility of FFR remains unclear in diabetic patients in view of the potential impact of the diffuse nature of vascular disease process. We aimed to study the relation between fractional flow reserve (FFR) values and long-term outcomes of diabetic and non-diabetic patients with deferred percutaneous coronary intervention (PCI). METHODS Patients with FFR assessment and deferred PCI (n=630) were enrolled and stratified according to diabetes mellitus (DM) status and FFR values. Patients were followed over a median of 39months. Cox proportional hazard regression models were used to analyze the association between clinical endpoints and clinical factors such as DM and FFR. RESULTS In non-diabetics (n=450), higher FFR values were associated with less cardiovascular events (hazard ratio (HR) for death and myocardial infarction (MI) [95% confidence interval (CI)], 0.61[0.44 to 0.86] per 0.1 increase in FFR, p=0.007; HR for revascularization [95%CI], 0.66[0.49 to 0.9] per 0.1 increase in FFR, p=0.006). In diabetics (n=180), there was no difference in death and MI across the range of FFR values. Among those patients with an FFR >0.85, diabetics had a more than two-fold higher risk of death and MI than non-diabetics (HR [95% CI], 2.20 [1.19 to 4.01], p=0.015). CONCLUSION Among non-diabetic patients with deferred PCI, a higher FFR was associated with lower rates of death, MI and revascularization. On the contrary in diabetic patients with deferred revascularization, FFR was not able to differentiate the risk of cardiovascular events.

The vasa vasorum in atherosclerosis: The vessel within the vascular wall

One of the leading causes of morbidity and mortality, acute coronary syndrome (ACS) often is caused by plaque rupture or erosion. It is, therefore, understandable that ongoing studies attempt to detect vulnerable plaque to understand the mechanism of plaque rupture and develop tools to predict

Clinical usefulness of nonhyperemic baseline Pd/Pa as a hybrid baseline Pd/Pa-fractional flow reserve strategy.

ObjectiveThe ratio of basal distal intracoronary pressure (Pd) and aortic pressure (Pa) is a nonhyperemic index for the severity of coronary artery stenosis. The aim of the current study was to evaluate the clinical usefulness of a hybrid baseline Pd/Pa–fractional flow reserve (FFR) strategy in reducing the need for hyperemia. MethodsIn this study, 570 lesions from 527 consecutive patients who had both baseline Pd/Pa and FFR determined were evaluated retrospectively. To evaluate the hybrid baseline Pd/Pa–FFR approach, patients were categorized into treatment, deferral, and undetermined groups on the basis of their baseline Pd/Pa. Thereafter, patients in the undetermined group were assigned to FFR-guided treatment or deferral on the basis of an FFR cutoff value of 0.80 or lower. Major adverse cardiac events were evaluated in a median of 48.8 months (interquartile range, 35.0–66.4). ResultsA hybrid strategy using a deferral baseline Pd/Pa value of 1.00 (negative predictive value of 100%) and a treatment baseline Pd/Pa value of 0.86 or lower (positive predictive value of 100%), and limiting adenosine to a baseline Pd/Pa value between 0.87 and 0.99 would prevent the need for vasodilator drugs in 14.6% of lesions (14.0% patients), maintaining 100% agreement with an FFR-only strategy. However, adenosine-free lesions are increased to 59.6%, with 91% agreement. There was no difference in the major adverse cardiac event-free survival rate at 5 years between baseline Pd/Pa-guided and FFR-guided treatment patients (70.8 vs. 76.3%, P=0.63), or between baseline Pd/Pa-guided and FFR-guided deferral patients (71.3 vs. 82.4%, P=0.99). ConclusionThe current study reports a range of baseline Pd/Pa values that can predict myocardial ischemia without the need for inducing hyperemia. Adoption of this hybrid baseline Pd/Pa–FFR approach can reduce the need for drug-induced hyperemia.

Attenuation in Peripheral Endothelial Function After Continuous Flow Left Ventricular Assist Device Therapy Is Associated With Cardiovascular Adverse Events

BACKGROUND Patients with heart failure (HF) have abnormal endothelial function. Although use of a continuous flow left ventricular assist device (CF-LVAD) results in significant hemodynamic improvement, the effects on systemic endothelial function are unclear. METHODS AND RESULTS Eighteen HF patients with CF-LVAD implantation were included in this prospective observational study. We measured reactive hyperemia index (RHI) before and after CF-LVAD implantation to evaluate sequential changes in endothelial function. Patients were followed clinically for the occurrence of adverse cardiovascular events, a composite of death, thrombosis, bleeding, HF, renal failure, and arrhythmia. Preoperative RHI was 1.77±0.39. Early in the postoperative period (7-14 days after operation) RHI significantly decreased to 1.19±0.31 (P<0.001, compared with preoperative RHI). At first and second follow-up (4-6 weeks and 3-7 months after operation) RHI remained lower at 1.48±0.50 (P=0.030) and 1.26±0.37 (P=0.002), respectively, compared with preoperative RHI. The decrease in early postoperative RHI relative to preoperative RHI was significantly associated with adverse cardiovascular events after CF-LVAD (age-adjusted risk ratio for 0.25 decrease in RHI, 1.35; 95% confidence interval: 1.13-1.62, P=0.001). CONCLUSIONS Peripheral endothelial function had a significant and persistent decline up to 5 months following implantation of CF-LVAD, and this decline was associated with adverse cardiovascular events. These findings may provide insight into some of the vascular complications following CF-LVAD in HF patients.

Left Internal Mammary Artery Versus Coronary Stents: Impact on Downstream Coronary Stenoses and Conduit Patency

Background The study compared downstream coronary and conduit disease progression in the left anterior descending coronary artery treated with coronary artery bypass grafting using the left internal mammary artery (LIMA) versus percutaneous coronary intervention with bare metal stent (BMS) or drug eluting stent (DES). Methods and Results A total of 12 301 consecutive patients underwent isolated primary coronary revascularization, of which 2386 met our inclusion criteria (Percutaneous coronary intervention, n=1450; coronary artery bypass grafting, n=936). Propensity score analysis matched 628 patients, of which 468 were treated to the left anterior descending with coronary artery bypass grafting with LIMA (n=314), percutaneous coronary intervention with BMS (n=94), and DES (n=60). Coronary angiograms were analyzed by quantitative coronary angiography (QCA; n=433). Cumulative downstream coronary and conduit disease progression were estimated by Kaplan–Meier method and effect of treatment type by Cox proportional hazard models. Patients treated with LIMA had significantly lower risk of downstream coronary disease progression at follow‐up angiogram compared with BMS and DES (hazard ratio [HR] [95% CI], 0.34; [0.20–0.59]; P=0.0002; and HR [95% CI], 0.39; [0.20–0.79]; P=0.01, respectively). LIMA was associated with a lower risk of conduit disease progression compared to BMS and DES (HR [95% CI], 0.18; [0.12–0.28]; P<0.001; and HR [95% CI], 0.27; [0.16–0.46]; P<0.001, respectively). BMS was associated with higher HR for downstream coronary and conduit disease progression compared with DES, but the difference did not reach statistical significance (HR [95% CI], 1.13; [0.57–2.36]; P=0.73; and HR [95% CI], 1.46; [0.88–2.50]; P=0.14, respectively). Conclusions LIMA grafting to left anterior descending is associated with significantly lower risk of downstream coronary and conduit disease progression compared to percutaneous coronary intervention with BMS and DES.