Near-Infrared Spectroscopy Intravascular-Ultrasound-Guided Intervention in Minimal Coronary Artery Stenosis: A Case Report.

Near-infrared spectroscopy intravascular ultrasounds (NIRS-IVUSs) can identify high-risk plaque morphologies associated with future event risk. However, the usage of NIRS-IVUSs is not universal. We report a case with insignificant coronary angiography (CAG) and high-risk NIRS-IVUS findings. A 58-year-old man with exertional dyspnea was admitted for a CAG evaluation. The CAG of the patient demonstrated mild angiographic stenosis in the mid-left anterior descending artery. However, NIRS-IVUS revealed a high maximum lipid core burden index at 4 mm (MaxLCBI4mm) and an intraluminal calcific protrusion with severe luminal stenosis at the lesion. Therefore, the patient was diagnosed as stable angina, and a drug-eluting stent was implanted in the lesion. A post-stent NIRS-IVUS demonstrated improved MaxLCBI4mm and significantly improved luminal stenosis. The patient did not have any procedural complications. In the present case, a patient with insignificant CAG demonstrated multiple high-risk features on NIRS-IVUS. Therefore, a percutaneous coronary intervention was performed. The presented case highlights the utility of NIRS-IVUS in nonobstructive CAG.

Effects of Acupuncture on Cardiac Remodeling in Patients with Persistent Atrial Fibrillation: Results of a Randomized, Placebo-Controlled, Patient- and Assessor-Blinded Pilot Trial and Its Implications for Future Research.

Background and Objectives: In this study, we attempted to determine the effects of acupuncture on cardiac remodeling and atrial fibrillation (AF) recurrence rates in patients with AF after electrical cardioversion (EC). Materials and Methods: We randomly assigned 44 patients with persistent AF to an acupuncture group or a sham acupuncture group. An electroacupuncture treatment session was administered once weekly for 12 weeks at four acupuncture points (left PC5, PC6, ST36, and ST37). Results: Among the 44 recruited participants, 16 (treatment group) and 15 (control group) completed the trial. The three-month AF recurrence rate (primary outcome) was not significantly different between the two groups. Following the completion of treatment, patients who had been treated with acupuncture had a significant reduction in left atrial volume index (42.2 ± 13.9 to 36.1 ± 9.7 mL/m2; p = 0.028), whereas no change in atrial size was observed in the sham acupuncture group. No serious adverse events were observed. The AF recurrence rate and cardiac function did not differ significantly between the two groups. At three months, the acupuncture treatment group showed more favorable atrial structural remodeling compared to the sham acupuncture group. Conclusion: In future research on acupuncture in AF management, it is recommended that the inclusion criteria be amended to include only symptomatic AF, that an appropriate control group is designed, and that the acupuncture treatment frequency is increased to several times per week.

Substance-P Prevents Cardiac Ischemia-Reperfusion Injury by Modulating Stem Cell Mobilization and Causing Early Suppression of Injury-Mediated Inflammation.

BACKGROUND/AIMS: Therapies using stem/progenitor cells have been experimentally and clinically investigated to regenerate damaged hearts. Substance-P (SP) induces bone marrow (BM) stem cell mobilization and suppresses inflammation in ischemic injuries. This study investigated the role of SP in BM stem cell mobilization and immune responses for tissue repair after ischemic-reperfusion injury (IRI), in comparison with that of granulocyte colony-stimulating factor (GCSF). METHODS: SP was intravenously injected into IRI rats and its affect was evaluated by determining colony forming efficiency, immune cell/ cytokine profiles, histological changes, and heart function through echocardiography. RESULTS: In the rat cardiac IRI model, SP suppressed IRI-mediated tumor necrosis factor-α induction, but increased the levels of interleukin-10, CD206+ monocytes, and regulatory T cells in the blood; reduced myocardial apoptosis at day 1 post-IRI; and markedly stimulated colony forming unit (CFU)-e and (CFU)-f cell mobilization. Efficacy of SP in the recovery of cardiac function after IRI was demonstrated by increased cardiac contractility, accompanied by reduced infarction sizes and fibrosis, and increased revascularization of vessels covered with alpha smooth muscle actin. These effects of SP were confirmed in an acute myocardial infarction (AMI) model. All effects mediated by SP were superior to those mediated by GCSF. CONCLUSION: Systemic injection of SP decreased early inflammatory responses and promoted stem cell mobilization, leading to a compact vasculature and improved cardiac function in cardiac IRI and AMI.

Efficacy and safety of electroacupuncture in acute decompensated heart failure: a study protocol for a randomized, patient- and assessor-blinded, sham controlled trial.

BACKGROUND: The purpose of this trial is to evaluate the effectiveness and safety of electroacupuncture in the treatment of acute decompensated heart failure compared with sham electroacupuncture. METHODS: This protocol is for a randomized, sham controlled, patient- and assessor-blinded, parallel group, single center clinical trial that can overcome the limitations of previous trials examining acupuncture and heart failure. Forty-four acute decompensated heart failure patients admitted to the cardiology ward will be randomly assigned into the electroacupuncture treatment group (n = 22) or the sham electroacupuncture control group (n = 22). Participants will receive electroacupuncture treatment for 5 days of their hospital stay. The primary outcome of this study is the difference in total diuretic dose between the two groups during hospitalization. On the day of discharge, follow-up heart rate variability, routine blood tests, cardiac biomarkers, high-sensitivity C-reactive protein (hs-CRP) level, and N-terminal pro b-type natriuretic peptide (NT-pro BNP) level will be assessed. Four weeks after discharge, hs-CRP, NT-pro BNP, heart failure symptoms, quality of life, and a pattern identification questionnaire will be used for follow-up analysis. Six months after discharge, major cardiac adverse events and cardiac function measured by echocardiography will be assessed. Adverse events will be recorded during every visit. DISCUSSION: The result of this clinical trial will offer evidence of the effectiveness and safety of electroacupuncture for acute decompensated heart failure. TRIAL REGISTRATION: Clinical Research Information Service: KCT0002249 .

Exenatide Prevents Morphological and Structural Changes of Mitochondria Following Ischaemia-Reperfusion Injury.

BACKGROUND: Exenatide exerts cardioprotective effects by attenuating ischaemic reperfusion (IR) injury, possibly through activating the opening of mitochondrial ATP-sensitive potassium channels. We used atomic force microscopy (AFM) to investigate changes in mitochondrial morphology and properties in order to assess exenatide-mediated cardioprotection in IR injury. METHODS: We used an in vivo Sprague-Dawley rat IR model and ex vivo Langendorff injury model. In the left anterior descending artery (LAD) occlusion model, animals were randomly divided into three groups: sham-operated rats (Sham, n=5), IR-injured rats treated with placebo (IR, n=6), and IR-injured treated with exenatide (IR + EXE, n=6). For the Langendorff model, rats were randomly divided into two groups: IR injury with placebo (IR, n=4) and IR injury with exenatide (IR+EXE, n=4). Morphological and mechanical changes of mitochondria were analysed by AFM. RESULTS: Exenatide pre-treatment improved cardiac function as evidenced by improvement in echocardiographic results. The ratio of infarct area (IA) to risk area (RA) was significantly reduced in exenatide-treated rats. According to AFM, IR significantly increased the area of isolated mitochondria, indicative of mitochondrial swelling. Treatment with exenatide reduced the mitochondrial area and ameliorated the adhesion force of mitochondrial surfaces. CONCLUSIONS: Exenatide pre-treatment improves morphological and mechanical characteristics of mitochondria in response to IR injury in a rat model. These alterations in mitochondrial characteristics appear to play a cardioprotective role against IR injury.

Platelet reactivity after receiving clopidogrel compared with ticagrelor in patients with kidney failure treated with hemodialysis: a randomized crossover study.

BACKGROUND: Patients with kidney failure treated with maintenance hemodialysis (HD) are poor responders to clopidogrel. More beneficial platelet-inhibiting strategies in HD patients therefore are required. STUDY DESIGN: Single-center, prospective, randomized, crossover study. SETTING & PARTICIPANTS: 25 HD patients in Seoul, Korea. INTERVENTION: Patients were randomly assigned to receive clopidogrel (300mg loading, 75mg once daily for maintenance dose) or ticagrelor (180mg loading, 90mg twice daily for maintenance dose) for 14 days, and after a 14-day washout period, crossover treatment for another 14 days. All patients received aspirin (100mg/d). OUTCOMES & MEASUREMENTS: Platelet function was evaluated predosing and at 1, 5, and 48 hours and 14 days after the first loading dose. During the offset phase, platelet function was assessed at 1 hour and 2, 4, and 14 days after the last dose by light transmittance aggregometry and the VerifyNow P2Y12 assay, and patients were genotyped for the CYP2C19*2 allele. Maximal extent of aggregation, inhibition of platelet aggregation (IPA), P2Y12 reaction units (PRUs), and percentage of inhibition were evaluated. We performed per-protocol analysis, excluding patients who did not complete the protocol. RESULTS: 9 patients did not complete the protocol (7 patients due to adverse events; 2, nonadherence). Higher IPA occurred with ticagrelor than with clopidogrel at 1, 5, and 48 hours and 14 days after loading. By 5 hours after loading, a greater proportion of patients in the ticagrelor group than in the clopidogrel group achieved IPA>50% (75% vs 12%, respectively; P<0.05) and IPA>70% (44% vs 0%, respectively; P<0.05). Rates (slope) of onset and offset of the antiplatelet effect were faster in patients receiving ticagrelor than for those receiving clopidogrel (P<0.05). Regardless of CYP2C19*2 allele, the ticagrelor group had significantly lower PRUs at all times than the clopidogrel group. LIMITATIONS: Single-center study with a small number of patients, not a double-blind study, and not intention-to-treat analysis. CONCLUSIONS: Ticagrelor may result in more rapid and greater platelet inhibition than clopidogrel in patients with kidney failure receiving HD.

Impact of lysophosphatidylcholine on survival and function of UEA-1(+)acLDL (+) endothelial progenitor cells in patients with coronary artery disease.

Lysophosphatidylcholine (LPC) generated from oxidized low-density lipoprotein by lipoprotein-associated phospholipase A2 plays a key role in plaque inflammation and vulnerability. Endothelial progenitor cells (EPCs) can repair injured endothelium and exert anti-inflammatory effects of vulnerable plaque. We study the impact and mechanisms of LPC on UEA-1 and acLDL binding EPCs (UEA-1(+)acLDL(+) EPCs). UEA-1(+)acLDL(+) EPCs from coronary artery disease (CAD) patients were cultured and exposed to LPC at different concentrations and different timepoints. We determined the significant concentration (40 µM). UEA-1(+)acLDL(+) EPCs were preincubated for 30 min with pravastatin (20 µM) with LY249002, a specific inhibitor of the Akt signaling pathway, and exposed for 24 h to LPC 40 µM. The survival, migration, adhesion, and proliferation of UEA-1(+)acLDL(+) EPCs were assessed. To examine the mechanisms of LPC toxicity and pravastatin effects, phosphorylated Akt and endothelial nitric oxide synthase (eNOS) levels and the ratio of Bcl-2/Bax protein expression were assessed. LPC induced apoptosis and impaired migration and adhesion of UEA-1(+)acLDL(+) EPCs significantly. The detrimental effects of LPC were attenuated by pravastatin. However, when UEA-1(+)acLDL(+) EPCs were pretreated with pravastatin and LY249002, a specific inhibitor of the Akt signaling pathway, simultaneously, the beneficial effects of pravastatin were abolished. Furthermore, LPC suppressed Akt and eNOS phosphorylation and increased Bcl-2/Bax expression. The effects of LPC on Akt/eNOS and Bcl-2/Bax activity were reversed by pravastatin. In conclusion, LPC inhibited UEA-1(+)acLDL(+) EPCs survival and impaired its functions, and these were attributable to inhibition of the Akt/eNOS and Bcl-2/Bax pathway. Pravastatin reversed the detrimental action of LPC. These findings suggest that LPC inhibition can be a possible strategy for CAD through EPC revitalization.

Effects of electroacupuncture on endothelial function and circulating endothelial progenitor cells in patients with cerebral infarction.

This study evaluated the effects of electroacupuncture (EA) on endothelial function and endothelial progenitor cells (EPC) in patients with cerebral infarction. In a randomized, placebo-controlled, crossover study, 20 patients with cerebral infarction were randomized into two treatment groups: EA or placebo. Before and after each intervention, pulse amplitude tonometry (PAT) was used to assess endothelial function and peripheral blood was analyzed for the number of EPCs. Circulating EPCs were quantified by flow cytometry as CD45(low) CD34(+) KDR2(+) cells. Plasma vascular endothelial growth factor (VEGF) and interleukin (IL)-10 levels were measured. Seven days later, crossover was performed on each group, with each group receiving the other treatment using the same protocol. The PAT hyperemia ratio ranged from 1.57 ± 0.41 to 2.04 ± 0.51 after EA, representing a significant improvement (P = 0.002); however, there was no improvement in the placebo group (P = 0.48). Circulating EPCs, as measured by flow cytometry, increased to 110.6 ± 74.3/100 µL in the EA group (P = 0.001) but did not change in the placebo group (45.9 ± 35.3/100 µL, P = 0.08). The increases in the number of EPCs and the PAT ratio after treatment were correlated (r = 0.78, P < 0.001). Plasma VEGF levels increased with EA compared to baseline (261.2 ± 34.0 vs 334.9 ± 80.5 pg/mL, P = 0.003). The number of circulating EPCs was positively correlated with plasma levels of VEGF (r = 0.50, P = 0.02). In conclusion, EA induced improvement of EPC levels and the PAT ratio in patients with cerebral infarction.

Cardioprotective effects of exenatide in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention: results of exenatide myocardial protection in revascularization study.

OBJECTIVE: Experimental evidence suggests that exenatide, a glucagon-like peptide 1 receptor analogue, has significant cardiovascular protective effects in various conditions. We examined whether routine use of exenatide at the time of primary percutaneous coronary intervention would reduce infarct size in patients with ST-segment-elevation myocardial infarction. APPROACH AND RESULTS: Fifty-eight patients with ST-segment-elevation myocardial infarction and thrombolysis in myocardial infarction flow 0 were enrolled in the study and randomly assigned to receive either exenatide or placebo (saline) subcutaneously. Infarct size was assessed by measuring the release of creatine kinase-MB and troponin I during 72 hours and by performing cardiac magnetic resonance imaging at 1 month after infarction. Routine and speckle tracking echocardiography was performed at initial presentation and at 3 days and 6 months after primary percutaneous coronary intervention. The exenatide and control groups had similar results with respect to ischemia time, demographic characteristics, and ejection fraction before primary percutaneous coronary intervention. The releases of creatine kinase-MB and troponin I were significantly reduced in the exenatide group. In 58 patients evaluated with cardiac magnetic resonance, the absolute mass of delayed hyperenhancement was significantly reduced in the exenatide group as compared with the control group (12.8±11.7 versus 26.4±11.6 g; P<0.01). At 6 months, the exenatide group showed a significantly lower value of E/E' with improved strain parameters. No significant adverse effects of exenatide administration were detected. CONCLUSIONS: In patients with ST-segment-elevation myocardial infarction, adjunctive exenatide therapy with primary percutaneous coronary intervention was associated with reduction of infarct size and improvement of subclinical left ventricular function.

Effects of sildenafil on nanostructural and nanomechanical changes in mitochondria in an ischaemia-reperfusion rat model.

Sildenafil exerts cardioprotective effects by activating the opening of mitochondrial ATP-sensitive potassium channels to attenuate ischaemia-reperfusion (IR) injury. In the present study, we used atomic force microscopy (AFM) to investigate changes in mitochondrial morphology and properties to assess sildenafil-mediated cardioprotection in a rat myocardial infarction model. To investigate the cardioprotective effects of sildenafil, we used an in vivo Sprague-Dawley rat model of IR. Rats were randomly divided into three groups: (i) sham-operated rats (control; n = 5); (ii) IR-injured rats treated with vehicle (normal saline; IR; n = 10); and (iii) IR-injured rats treated with 0.75 mg/kg, i.p., sildenafil (IR + Sil; n = 10). Morphological and mechanical changes to mitochondria were analysed by AFM. Infarct areas were significantly reduced in sildenafil-treated rats (7.8 ± 3.9% vs 20.4 ± 7.0% in the sildenafil-treated and untreated IR groups, respectively; relative reduction 62%; P < 0.001). Analysis of mitochondria by AFM showed that IR injury significantly increased the areas of isolated mitochondria compared with control (24 150 ± 18 289 vs 1495 ± 1139 nm(2) , respectively; P < 0.001), indicative of mitochondrial swelling. Pretreatment with sildenafil before IR injury reduced the mitochondrial areas (7428 ± 3682 nm(2) ; P < 0.001; relative reduction 69.2% compared with the IR group) and ameliorated the adhesion force of mitochondrial surfaces. Together, these results suggest that sildenafil has cardioprotective effects against IR injury in a rat model by improving the morphological and mechanical characteristics of mitochondria.

Device Closure or Antithrombotic Therapy After Cryptogenic Stroke in Elderly Patients With a High-Risk Patent Foramen Ovale.

BACKGROUND AND PURPOSE: In young patients (aged 18-60 years) with patent foramen ovale (PFO)-associated stroke, percutaneous closure has been found to be useful for preventing recurrent ischemic stroke or transient ischemic attack (TIA). However, it remains unknown whether PFO closure is also beneficial in older patients. METHODS: Patients aged ≥60 years who had a cryptogenic stroke and PFO from ten hospitals in South Korea were included. The effect of PFO closure plus medical therapy over medical therapy alone was assessed by a propensity-score matching method in the overall cohort and in those with a high-risk PFO, characterized by the presence of an atrial septal aneurysm or a large shunt. RESULTS: Out of the 437 patients (mean age, 68.1), 303 (69%) had a high-risk PFO and 161 (37%) patients underwent PFO closure. Over a median follow-up of 3.9 years, recurrent ischemic stroke or TIA developed in 64 (14.6%) patients. In the propensity score-matched cohort of the overall patients (130 pairs), PFO closure was associated with a significantly lower risk of a composite of ischemic stroke or TIA (hazard ratio [HR]: 0.45; 95% confidence interval [CI]: 0.24-0.84; P=0.012), but not for ischemic stroke. In a subgroup analysis of confined to the high-risk PFO patients (116 pairs), PFO closure was associated with significantly lower risks of both the composite of ischemic stroke or TIA (HR: 0.40; 95% CI: 0.21-0.77; P=0.006) and ischemic stroke (HR: 0.47; 95% CI: 0.23-0.95; P=0.035). CONCLUSION: Elderly patients with cryptogenic stroke and PFO have a high recurrence rate of ischemic stroke or TIA, which may be significantly reduced by device closure.

Efficacy and safety of combination therapy with telmisartan, rosuvastatin, and ezetimibe in patients with dyslipidemia and hypertension: A randomized, double-blind, multicenter, therapeutic confirmatory, phase III clinical trial.

This study aimed to compare and evaluate the efficacy of the blood pressure (BP) control and cholesterol-lowering effects and safety of combination therapy with telmisartan, rosuvastatin, and ezetimibe versus rosuvastatin and ezetimibe double therapy or telmisartan single therapy in dyslipidemia patients with hypertension. After a wash-out/therapeutic lifestyle change period of ≥4 weeks, a total of 100 eligible patients were randomized and received one of three treatments for 8 weeks: (1) telmisartan 80 mg/rosuvastatin 20 mg/ezetimibe 10 mg (TRE), (2) rosuvastatin 20 mg/ezetimibe 10 mg (RE), or (3) telmisartan 80 mg (T). The primary endpoint was the efficacy evaluation of TRE by comparing changes in mean sitting systolic blood pressure (msSBP) and mean percentage change in low-density lipoprotein-C (LDL-C) from baseline after 8 weeks of treatment. The least square (LS) mean (SE) changes in msSBP at 8 weeks compared with baseline were -23.02 (3.04) versus -7.18 (3.09) mmHg in the TRE and RE groups, respectively (p < .0001), and -25.80 (2.74) versus -14.92 (2.65) mmHg in the TRE and T groups, respectively (p = .0005). The percentage changes in the mean (SD) LDL-C at 8 weeks compared with baseline were -54.97% (3.49%) versus -0.17% (3.23%) in the TRE and T groups, respectively (p < .0001). No serious adverse events occurred, and no statistically significant differences in the incidence of overall AEs and adverse drug reactions occurred among the three groups. TRE therapy significantly decreased msSBP and LDL-C compared to RE or T therapy with comparable safety and tolerability profiles.

Preventive effects of exenatide on endothelial dysfunction induced by ischemia-reperfusion injury via KATP channels.

OBJECTIVE: The purpose of this study was to evaluate whether exenatide administration can prevent impairment in endothelium-dependent vasodilatation induced by ischemia-reperfusion (IR) injury and whether this effect is mediated by K(ATP) channel opening. METHODS AND RESULTS: In a double-blind, placebo-controlled, crossover design, 20 volunteers were randomly assigned to 2 groups: subcutaneous exenatide (10 µg) or placebo administration. At 30 minutes after the study drug administration, endothelium-dependent flow-mediated dilatation (FMD) of the radial artery was measured before and after IR (15 minutes of ischemia at the level of the brachial artery followed by 15 minutes of reperfusion) injury. Seven days later, both groups were crossed over and received the other treatment (ie, placebo or exenatide) and underwent the same protocol. Pre-IR radial artery diameter, FMD, and baseline radial artery diameter after IR injury were similar between 2 groups (P=no significant difference). After placebo administration, IR significantly blunted FMD (before IR: 12.0±6.23%; after IR: 4.6±3.57%, P=0.02). Exenatide prevented this impairment (FMD before IR: 15.0±7.14%; FMD after IR: 15.0±5.96%, P=no significant difference; P<0.001 compared with placebo). In a separate protocol, this protective effect was completely abolished by pretreatment with glibenclamide (glyburide, 5 mg), a blocker of K(ATP) channels (n=7; FMD before IR: 12.0±2.2%; after IR: 3.2±2.1%, P<0.001). CONCLUSIONS: The present study demonstrates that subcutaneous exenatide protects IR-induced endothelial dysfunction through opening of K(ATP) channels in human IR injury model.

Percutaneous coronary intervention for acute myocardial infarction in elderly patients with renal dysfunction: results from the Korea Acute Myocardial Infarction Registry.

This study aimed to evaluate the effects of percutaneous coronary intervention (PCI) on short- and long-term major adverse cardiac events (MACE) in elderly (>75 yr old) acute myocardial infarction (AMI) patients with renal dysfunction. As part of Korea AMI Registry (KAMIR), elderly patients with AMI and renal dysfunction (GFR<60 mL/min) received either medical (n=439) or PCI (n=1,019) therapy. Primary end point was in-hospital death. Secondary end point was MACE during a 1 month and 1 yr follow-up. PCI group showed a significantly lower incidence of in-hospital death (20.0% vs 14.3%, P=0.006). Short-term and long-term MACE rates were higher in medical therapy group (31.9% vs 19.0%; 57.7% vs 31.3%, P<0.001), and this difference was mainly attributed to cardiac death (29.3% vs 17.6%; 51.9% vs 25.0%, P<0.001). MACE-free survival time after adjustment was also higher in PCI group on short-term (hazard ratio, 0.67; confidence interval, 0.45-0.98; P=0.037) and long-term follow-up (hazard ratio, 0.61, confidence interval, 0.45-0.83; P=0.002). In elderly AMI patients with renal dysfunction, PCI therapy yields favorable in-hospital and short-term and long-term MACE-free survival.

Effect of vitamin D on endothelial and ventricular function in chronic heart failure patients: A prospective, randomized, placebo-controlled trial.

BACKGROUND: Low 25-hydroxyvitamin D (25OHD) levels are common in patients with chronic heart failure (HF) and are associated with increased mortality risk. This study aimed to establish the safety and efficacy of oral vitamin D3 (cholecalciferol) supplementation and its effect on endothelial and ventricular function in patients with stable HF. METHODS: This study was an investigator-initiated, multicenter, prospective, randomized, placebo-controlled trial. Seventy-three HF patients with 25OHD levels < 75 nmol/L (30 ng/mL) were randomized to receive 4000 IU vitamin D daily or a placebo for 6 months. The primary endpoint was a change in endothelial function between the baseline and after 6 months as assessed using EndoPAT. Secondary endpoints included changes in echocardiographic parameters and differences in quality of life (6-min walking test and New York Heart Association functional status) at 6 months. RESULTS: There were no adverse events in either group during the study period. Vitamin D supplementation did not improve endothelial dysfunction (EndoPAT: baseline, 1.19 ± 0.4 vs 6 months later, 1.22 ± 0.3, P = .65). However, patients' blood pressure, 6-min walking distance, and EQ-5D questionnaire scores improved after vitamin D treatment. In addition, a significant reduction in the left atrial diameter was observed. CONCLUSION: A daily vitamin D dose of 4000 IU for chronic HF appears to be safe. This dosage did not improve endothelial function but did improve the 6-min walk distance, symptoms, and left atrial diameter at 6 months.

Efficacy and Safety of Da-Chai-Hu-Tang in Lipid Profiles in High-Risk, Statin-Treated Patients with Residual HyperTG: A 12-Week, Randomized, Active-Control, Open Clinical Study.

Da-Chai-Hu-Tang (DCHT) is a herbal extract that has been shown to reduce serum triglyceride (TG) levels in animal experiments as well as small clinical trials. This study aimed to evaluate the efficacy and safety of DCHT in high-risk, statin-treated patients with residual hypertriglyceridemia (hyperTG). This was a 12-week, randomized, active-controlled, open-label, single-center trial. Of these patients, 42 had high cardiovascular risks whose LDL cholesterol levels were controlled by statin treatment; however, with TG levels of 200 to 500 mg/dL they were randomly assigned 1:1 to the OMEGA3 or DCHT group. The primary endpoint was defined as the percentage change in TG at 12 weeks, and changes in other lipid profiles and endothelial cell function were included as secondary endpoints. Safety analyses were also conducted. In the OMEGA3 group, the average TG level decreased from 294.5 ± 72.0 to 210.0 ± 107.8 mg/dL (p = 0.004), and in the DCHT group, from 288.7 ± 59.1 to 227.5 ± 98.1 mg/dL (p = 0.001). The percentage change in TG was -27.6 ± 33.6 and -22.4 ± 24.1 (p = 0.58), respectively, and there was no significant difference between the two groups. There were no severe adverse events in either group. In high-risk, statin-treated patients with residual hyperTG, the administration of OMEGA3 or DCHT for 12 weeks resulted in a significant reduction in TG, and the effect of DCHT was not inferior to that of OMEGA3.

The sGC-cGMP Signaling Pathway as a Potential Therapeutic Target in Doxorubicin-Induced Heart Failure: A Narrative Review.

The anti-cancer agent doxorubicin (DOX) has high cardiotoxicity that is linked to DOX-mediated increase in oxidative stress, mitochondrial iron overload, DNA damage, autophagy, necrosis, and apoptosis, all of which are also associated with secondary tumorigenicity. This limits the clinical application of DOX therapies. Previous studies have attributed DOX-mediated cardiotoxicity to mitochondrial iron accumulation and the production of reactive oxygen species (ROS), which seem to be independent of its anti-tumor DNA damaging effects. Chemo-sensitization of soluble guanylate cyclase (sGC) in the cyclic guanosine monophosphate (cGMP) pathway induces tumor cell death despite the cardiotoxicity associated with DOX treatment. However, sGC-cGMP signaling must be activated during heart failure to facilitate myocardial cell survival. The sGC pathway is dependent on nitric oxide and signal transduction via the nitric oxide-sGC-cGMP pathway and is attenuated in various cardiovascular diseases. Additionally, cGMP signaling is regulated by the action of certain phosphodiesterases (PDEs) that protect the heart by inhibiting PDE, an enzyme that hydrolyses cGMP to GMP activity. In this review, we discuss the studies describing the interactions between cGMP regulation and DOX-mediated cardiotoxicity and their application in improving DOX therapeutic outcomes. The results provide novel avenues for the reduction of DOX-induced secondary tumorigenicity and improve cellular autonomy during DOX-mediated cardiotoxicity.

Acute Effect of Evolocumab on Lipoprotein(a) Level and Inflammation in Patients with Coronary Artery Disease.

Background: Several studies have shown that high plasma lipoprotein(a) concentrations are associated with an increased risk of arteriosclerotic cardiovascular disease. Thus, Lp(a) has emerged as a new therapeutic target. Circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are new lipid-lowering agents that reduce low-density lipoprotein cholesterol as well as Lp(a). Methods: We analyzed the short-term effects of one-time administration of evolocumab (a PCSK9 inhibitor) on the lipid profiles (especially Lp(a)) and inflammatory markers in Korean patients with coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI). Sixty-four patients with CAD who underwent PCI were enrolled in this trial. Evolocumab (140 mg) was administered to patients within 24 h after PCI. Lipid profiles and inflammatory marker levels were measured at baseline and 2 weeks later. Results: The PCSK9 inhibitor significantly reduced the baseline levels of Lp(a) (−9.2 mg/dL, p < 0.001), but high-sensitivity C-reactive protein (+0.07 mg/dL, p = 0.272) was not significantly different after 2 weeks. In patients with an Lp(a) level of 50 mg/dL or more, the Lp(a) level decreased significantly by approximately 30%, from 95.6 mg/dL to 67.0 mg/dL (p < 0.001). Conclusions: One-time PCSK9 inhibitor treatment may be effective in lowering Lp(a) levels in Korean patients in the short term.

Correlations Between Coronary Artery Disease, Coronary Artery Calcium Score, and Lipoprotein(a) Level in Korea.

Background: Lipoprotein(a) (Lp(a)) levels are associated with coronary artery disease (CAD) and aortic valve calcification. This study aimed to determine the correlation between Lp(a) levels and coronary artery calcium (CAC) scores in patients who underwent coronary computed tomography angiography (CCTA). Methods: This was a single-center observational study. The patients had not been previously diagnosed with CAD and underwent CCTA and Lp(a) measurement in a three-month timeframe. Coronary angiography and further management were performed according to the physician's decision. Of the 252 patients, 81 and 171 patients underwent coronary revascularization and received medical treatment only, respectively. To examine the relationship between Lp(a) and CAC score and between Lp(a) and CAD, we divided the patients by Lp(a) level (50 mg/dL) and CAC score (400). Results: No relationship was observed between Lp(a) and CAD or other risk factors for CAD. There were no differences in the ratio of patients who underwent coronary revascularization or in the CAC score according to an Lp(a) level of 50 mg/dL. There was no difference in Lp(a) level at a CAC score of 400. The proportion of patients who underwent coronary revascularization was high in the high CAC score group (50.6% vs 23.7%, p = 0.000). No association was observed between Lp(a) level and CAC score in the Spearman correlation (0.000, p < 0.998). Conclusion: Correlations between Lp(a) level and CAC score and between Lp(a) and CAD were not observed in this Korean cohort study. However, a high CAC score was correlated with coronary revascularization.

Platelet reactivity in patients with chronic kidney disease receiving adjunctive cilostazol compared with a high-maintenance dose of clopidogrel: results of the effect of platelet inhibition according to clopidogrel dose in patients with chronic kidney disease (PIANO-2 CKD) randomized study.

BACKGROUND: Chronic kidney disease (CKD) is a factor of low response to clopidogrel. We sought to assess the functional impact of cilostazol in CKD patients with undergoing hemodialysis. METHODS: Seventy-four patients with CKD undergoing hemodialysis and percutaneous coronary intervention were enrolled. Patients were randomly assigned to receive clopidogrel (75 mg/d [group 1, n = 24]), high-maintenance dose of clopidogrel (150 mg/d [group 2, n = 25]), or clopidogrel (75 mg/d) with cilostazol (200 mg/d [group 3, n = 25]) for 14 days. Another 50 patients with normal renal function undergoing percutaneous coronary intervention were treated with 75 mg of clopidogrel and served as the control group. Platelet function was evaluated before and after antiplatelet therapy with light transmittance aggregometry and with VerifyNow P2Y12 assay (Accumetrics, San Diego, CA). Platelet activation markers (soluble CD40 ligand and soluble P-selectin) were also assessed. RESULTS: The baseline platelet function measurements were similar in the 3 groups of patients; however, the CKD groups had significantly higher platelet aggregation activity compared with the control groups. The rate of high on-treatment platelet reactivity was significantly lower in group 3 than in groups 1 and 2 (10% vs 43% vs 32%, respectively; P < .05). After 14 days of antiplatelet therapy, the changes in plasma soluble CD40 ligand and soluble P-selectin levels were significantly higher in group 3 compared with groups 1 and 2 (P < .01); however, there were no significant differences in platelet function and activation markers between groups 1 and 2. CONCLUSIONS: Adjunctive cilostazol improves platelet inhibition compared with 75 or 150 mg of clopidogrel in CKD patients undergoing hemodialysis.