Yung Ta Kao

Extracorporeal membrane oxygenation–assisted primary percutaneous coronary intervention may improve survival of patients with acute myocardial infarction complicated by profound cardiogenic shock

PURPOSE The aim of this study was to evaluate the impact of extracorporeal membrane oxygenation (ECMO) assistance on the clinical outcome of patients with acute myocardial infarction (AMI) that is complicated by profound cardiogenic shock (CS) who received primary percutaneous coronary intervention (PCI). MATERIALS AND METHODS We collected patients from January 2004 through December 2006 (stage 1); 25 patients who presented with AMI and received primary PCI and had profound CS were enrolled in the study. Intraaortic balloon counterpulsation (IABP) was the only modality for extracorporeal support in our hospital. From January 2007 through December 2009 (stage 2), 33 patients who presented with AMI and received primary PCI and had profound CS were enrolled; for this stage; both intra-aortic balloon counter-pulsation and ECMO support were available in our facility. RESULTS A Kaplan-Meier survival analysis displayed significantly improved survival for patients in stage 2 (P = .001; 1-year survival in stage 1 vs 2; 24% vs 63.64%). Patients presenting with either STEMI (ST segment elevation myocardial infarction) or NSTEMI (Non-ST segment elevation myocardial infarction) benefited from ECMO-assisted PCI (P < .05). In stage 1, patients with refractory ventricular tachycardia/ventricular fibrillation had a very low survival rate; however, in stage 2, the survival rate of patients with and without refractory ventricular tachycardia/ventricular fibrillation was similar (P = .316). CONCLUSION Extracorporeal membrane oxygenation-assisted PCI for patients with AMI that is complicated by profound CS may improve the 30-day and 1-year survival rates.

Dipeptidyl peptidase-4 inhibitor improves neovascularization by increasing circulating endothelial progenitor cells

BACKGROUND AND PURPOSE Current methods used to treat critical limb ischaemia (CLI) are hampered by a lack of effective strategies, therefore, therapeutic vasculogenesis may open up a new field for the treatment of CLI. In this study we investigated the ability of the DPP‐4 inhibitor, sitagliptin, originally used as a hypoglycaemic agent, to induce vasculogenesis in vivo.

MK-0626, A Dipeptidyl Peptidase-4 Inhibitor, Improves Neovascularization by Increasing Both the Number of Circulating Endothelial Progenitor Cells and Endothelial Nitric Oxide Synthetase Expression

Current treatment modalities for critical limb ischemia (CLI) are of limited benefit; therefore, advances in therapeutic vasculogenesis may open an important new avenue for the treatment of CLI. This study examines the therapeutic potential of the DPP-4 inhibitor MK-0626 as a regulator of vasculogenesis in vivo. MK-0626 was administered daily to C57CL/B6 mice and eGFP-labeled bone marrow-transplanted ICR mice that had undergone hind limb ischemia surgery. Laser Doppler imaging and flow cytometry were used to evaluate the degree of neo-vasculogenesis and the number of circulating endothelial progenitor cells (EPCs), respectively. Cell surface markers of EPCs and the level of endothelial nitric oxide synthase (eNOS) were studied in the vessels. Mice that received MK-0626 had an elevated level of glucagon- like peptide-1 (GLP-1) and a decreased level of dipeptidyl peptidase-4 (DPP-4) in their plasma, in addition to an ischemia-induced increase in the level of stromal cell-derived factor-1 (SDF-1). In C57CL/B6 mice, blood flow in the ischemic limb was significantly improved by treatment with MK-0626. The number of circulating EPCs and both the synthesis and phosphorylation of eNOS were also increased in ischemic thigh muscle after MK-0626 treatment. In contrast, similar effects of MK-0626 were not observed in B6.129P2-Nos3(tm1Unc)/J mice (an eNOS knockout mouse). Additionally, MK-0626 treatment promoted the mobilization and homing of EPCs to ischemic tissue in eGFP transgenic mouse bone marrow-transplanted ICR mice. We conclude that both the number of circulating EPCs and neo-vasculogenesis are increased in response to DPP-4 inhibitor treatment and that this occurs via an eNOS-dependent mechanism. The results highlight the therapeutic vasculogenesis potential of the DPP-4 inhibitor MK-0626 using a hind limb ischemia mouse model.

Ambulatory pulse pressure as a novel predictor for long-term prognosis in essential hypertensive patients.

The prognostic value of ambulatory blood pressure (BP) monitoring for long-term prognosis varies in recent studies. The study aimed to investigate the role of ambulatory BP parameters in mortality and cardiovascular (CV) events in hypertensive patients. A series of 412 participants (59.3±4.0 years) who received ambulatory BP monitoring for their fluctuated BP, either untreated or treated since 1995, were enroled. The mortality and CV events were obtained by follow-up and linked to the National Death Registry in Taiwan. There were 233 untreated and 179 treated patients. The latter were older with more comorbidity when compared with the former. After follow-up for 8.5±1.7 years, both ambulatory systolic BP and pulse pressure (PP) could predict all-cause mortality, non-CV mortality, CV disease and stroke after adjusting for baseline covariates. However, only ambulatory PP could predict CV mortality and coronary heart disease. Ambulatory PP is better than ambulatory systolic BP, particularly in prediction of all-cause mortality. There was no predictive value of office BP in any outcome. In conclusion, ambulatory PP is a good predictor for long-term outcomes in hypertensive patients. The parameters of ambulatory rather than office BP could be applied for risk stratification either before or under antihypertensive treatment.

Statins, HMG-CoA reductase inhibitors, improve neovascularization by increasing the expression density of CXCR4 in endothelial progenitor cells

Statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, are used to reduce cholesterol biosynthesis in the liver. Accordingly, statins regulate nitric oxide (NO) and glutamate metabolism, inflammation, angiogenesis, immunity and endothelial progenitor cells (EPCs) functions. The function of EPCs are regulated by stromal cell-derived factor 1 (SDF-1), vascular endothelial growth factor (VEGF), and transforming growth factor β (TGF-β), etc. Even though the pharmacologic mechanisms by which statins affect the neovasculogenesis of circulating EPCs, it is still unknown whether statins affect the EPCs function through the regulation of CXCR4, a SDF-1 receptor expression. Therefore, we desired to explore the effects of statins on CXCR4 expression in EPC-mediated neovascularization by in vitro and in vivo analyses. In animal studies, we analyzed the effects of atorvastatin or rosuvastatin treatments in recovery of capillary density and blood flow, the expression of vWF and CXCR4 at ischemia sites in hindlimb ischemia ICR mice. Additionally, we analyzed whether the atorvastatin or rosuvastatin treatments increased the mobilization, homing, and CXCR4 expression of EPCs in hindlimb ischemia ICR mice that underwent bone marrow transplantation. The results indicated that statins treatment led to significantly more CXCR4-positive endothelial progenitor cells incorporated into ischemic sites and in the blood compared with control mice. In vivo, we isolated human EPCs and analyzed the effect of statins treatment on the vasculogenic ability of EPCs and the expression of CXCR4. Compared with the control groups, the neovascularization ability of EPCs was significantly improved in the atorvastatin or rosuvastatin group; this improvement was dependent on CXCR4 up-regulation. The efficacy of statins on improving EPC neovascularization was related to the SDF-1α/CXCR4 axis and might be regulated by the NO. In conclusion, atorvastatin and rosuvastatin improved neovascularization in hindlimb ischemia mice; this effect may have been mediated by increased CXCR4 expression in EPCs.

Higher post-acute myocardial infarction plasma haptoglobin level is associated with poor long-term overall survival

AIM To evaluate the association of post-acute myocardial infarction (AMI) plasma haptoglobin (Hp) levels with long-term overall survival in AMI patients. METHODS AND RESULTS Patients who were diagnosed of AMI were recruited and their Hp phenotypes and plasma levels were determined. According to previously reported cutoff point for Hp level (288.4ng/ml), patients were classified as higher Hp group (>288.4ng/ml) and lower Hp group (≤288.4ng/ml). The primary outcome was overall survival. This study recruited and followed a total of 117 patients for a median of 11.0 (3.2-17.6) years. Higher Hp group had 46 patients (39.3%) and lower Hp group had 71 patients (60.7%). Twelve patients had Hp 1-1 (10.3%), 50 with Hp 2-1 (42.7%), and 55 with Hp 2-2 (47.0%). The lower Hp group had significantly better overall survival (174.1 [51.6-212.5] vs. 106.5 [22.2-209.1], P=0.037). There was no significant difference in overall survival between the three phenotype groups (P=0.477). Multivariate regression analysis revealed that increased age (adjusted HR=1.06, 95% CI: 1.03-1.10, P<0.001) and higher Hp level (adjusted HR=1.65, 95%=1.02-2.67, P=0.040) were significantly associated with poor overall survival. CONCLUSION Higher post-AMI plasma Hp level was independently associated with poor overall survival in AMI patients. No significant difference in overall survival was noted between three Hp phenotype groups. Acute phase Hp level might reflect the severity of oxidative stress during inflammation process.

An endoluminal aortic prosthesis infection presenting as pneumoaorta and aortoduodenal fistula

Herein, we present a case of pneumoaorta and aortoduodenal fistula (ADF) caused by an endoluminal aortic prosthesis infection. An 82-year-old man underwent endovascular aneurysm repair with a stent graft to exclude a 5.1-cm abdominal aortic aneurysm. Three months after the index procedure, the patient was taken to the emergency department at a medical university hospital. He presented with a 2-d history of bloody diarrhea. An endoluminal aortic stent graft infection was diagnosed, and an ADF was identified. The patient died of septic shock despite emergency surgery and intensive care. When encountered, stent graft infections require appropriate antibiotics and graft explantation. The diagnosis of an ADF is important, and surgery remains the most effective management if septic shock presents despite conservative treatment.

Association between renin-angiotensin-aldosterone system blockade and future osteoporotic fracture risk in hypertensive population a population-based cohort study in Taiwan

Abstract Tissue renin–angiotensin–aldosterone system (RAAS) activation in sites of osteoporosis had been demonstrated in animal studies; however, the possibility of RAAS blockade to prevent future osteoporotic fracture had rarely been verified in clinical studies. We Used the Taiwan Longitudinal Health insurance database 2000 to 2008, the cohort study comprised patients age over 40 with a recorded new diagnosis of hypertension between January 1, 2000 to December 31, 2008, in addition, patients who had diagnosis of osteoporosis before the date of cohort enter were excluded. After the definite diagnosis of hypertension, each patient was followed until osteoporotic fracture happened or the end of 2008. The occurrence of osteoporotic fracture was evaluated in patients who either were or without taking RAAS blockade agents. Cox proportional hazard regressions were used to evaluate the osteoporotic fracture incidence after adjusting for known confounding factors. In total, 57,132 hypertensive patients comprised the study cohort. Our study results showed that the incidence of osteoporosis fracture in the whole cohort was significantly higher in the RAAS blockade non-user group than the user group. This phenomenon was observed in both sex and all age categories. Sensitivity analysis further showed the concordant lower osteoporosis fracture risk in patients with various RAAS blockers usage durations; the risk of osteoporosis fracture was the lowest in those drug use >365 days when compared with the non-user cohort. In conclusion, our study result demonstrated the lower future osteoporotic fracture risk in hypertensive subjects who received long term RAAS blocker treatment.

Subacute bacterial endocarditis presenting as left upper quadrant abdominal pain

Infective endocarditis is a microbial infection of the endocardial surface of the heart. Its symptoms and signs are varied, and include fever, heart murmur, peripheral embolism, and heart failure. The diagnosis of subacute bacterial endocarditis (SBE) is suggested by a history of an indolent process characterized by fever, fatigue, anorexia, and unexplained weight loss. These patients may have had an invasive procedure, such as dental work, or abused intravenous drugs prior to the diagnosis of SBE. Although uncommon, the patients may present with nonspecific symptoms caused by peripheral embolic events. Herein, we report a 25-year-old male diagnosed with SBE, who presented with the unusual symptom of sudden onset of left upper quadrant abdominal pain for 2 days. His clinical history is also discussed.