Goreisan as a successful adjuvant therapy of heart failure with preserved ejection fraction and advanced chronic kidney disease: a case report.

Atrial functional mitral and tricuspid regurgitation due to atrial fibrillation (AF) are common causes of heart failure with preserved ejection fraction, but standard treatment with conventional diuretics can often lead to renal dysfunction. Kampo Goreisan, a traditional Eastern-Asian herbal medicine that regulates body water balance via the aquaporin-incorporated water reabsorption system can be used as an alternative therapy without causing renal burden. In this report, we describe a case of successful treatment with Goreisan of heart failure with preserved ejection fraction (HFpEF) due to atrial functional mitral and tricuspid regurgitation (AFMR/TR) receiving guideline-directed medical-therapy. Goreisan could afford amelioration of regurgitation and improvement bilateral systolic ventricular function without renal dysfunction. Thus, Goreisan may be a promising therapeutic option for patients refractory to conventional diuretics.

Lysophosphatidylserine induces necrosis in pressure overloaded male mouse hearts via G protein coupled receptor 34.

Heart failure is a leading cause of mortality in developed countries. Cell death is a key player in the development of heart failure. Calcium-independent phospholipase A2ß (iPLA2ß) produces lipid mediators by catalyzing lipids and induces nuclear shrinkage in caspase-independent cell death. Here, we show that lysophosphatidylserine generated by iPLA2ß induces necrotic cardiomyocyte death, as well as contractile dysfunction mediated through its receptor, G protein-coupled receptor 34 (GPR34). Cardiomyocyte-specific iPLA2ß-deficient male mice were subjected to pressure overload. While control mice showed left ventricular systolic dysfunction with necrotic cardiomyocyte death, iPLA2ß-deficient mice preserved cardiac function. Lipidomic analysis revealed a reduction of 18:0 lysophosphatidylserine in iPLA2ß-deficient hearts. Knockdown of Gpr34 attenuated 18:0 lysophosphatidylserine-induced necrosis in neonatal male rat cardiomyocytes, while the ablation of Gpr34 in male mice reduced the development of pressure overload-induced cardiac remodeling. Thus, the iPLA2ß-lysophosphatidylserine-GPR34-necrosis signaling axis plays a detrimental role in the heart in response to pressure overload.

Rubicon-regulated beta-1 adrenergic receptor recycling protects the heart from pressure overload.

Heart failure has high morbidity and mortality in the developed countries. Autophagy is important for the quality control of proteins and organelles in the heart. Rubicon (Run domain Beclin-1-interacting and cysteine-rich domain-containing protein) has been identified as a potent negative regulator of autophagy and endolysosomal trafficking. The aim of this study was to investigate the in vivo role of Rubicon-mediated autophagy and endosomal trafficking in the heart. We generated cardiomyocyte-specific Rubicon-deficient mice and subjected the mice to pressure overload by means of transverse aortic constriction. Rubicon-deficient mice showed heart failure with left ventricular dilatation, systolic dysfunction and lung congestion one week after pressure overload. While autophagic activity was unchanged, the protein amount of beta-1 adrenergic receptor was decreased in the pressure-overloaded Rubicon-deficient hearts. The increases in heart rate and systolic function by beta-1 adrenergic stimulation were significantly attenuated in pressure-overloaded Rubicon-deficient hearts. In isolated rat neonatal cardiomyocytes, the downregulation of the receptor by beta-1 adrenergic agonist was accelerated by knockdown of Rubicon through the inhibition of recycling of the receptor. Taken together, Rubicon protects the heart from pressure overload. Rubicon maintains the intracellular recycling of beta-1 adrenergic receptor, which might contribute to its cardioprotective effect.

Administration of a TLR9 Inhibitor Attenuates the Development and Progression of Heart Failure in Mice.

Mitochondrial deoxyribonucleic acid, containing the unmethylated cytidine-phosphate-guanosine motif, stimulates Toll-like receptor 9 to induce inflammation and heart failure. A small chemical, E6446 [(6-[3-(pyrrolidin-1-yl)propoxy)-2-(4-(3-(pyrrolidin-1-yl)propoxy)phenyl]benzo[d]oxazole)], is a specific Toll-like receptor 9 inhibitor in cardiomyocytes. In this study, we showed that E6446 exerts beneficial effects for the prevention and treatment of pressure overload-induced heart failure in mice. When administered before the operation and chronically thereafter, E6446 prevented the development of left ventricular dilatation as well as cardiac dysfunction, fibrosis, and inflammation. Furthermore, when administered after the manifestation of cardiac dysfunction, E6446 slowed progression of cardiac remodeling. Thus, the inhibitor may be a novel therapeutic agent for treating patients with heart failure.

Angioplasty of the Occluded Persistent Sciatic Artery Using the Retrograde Approach from Superficial Femoral Artery.

Persistent sciatic artery is a rare developmental anomaly prone to atherosclerotic disease. We present a case of successful endovascular therapy for left persistent sciatic artery that was occluded at the distal site. The angioplasty was performed with both antegrade approach from contralateral common femoral artery and retrograde approach from ipsilateral superficial femoral artery. The guidewire was advanced via collateral channel and crossed through the lesion retrogradely. Rendez-vous technique was performed, and the lesion was successfully dilated by balloon inflation. Angioplasty of occluded sciatic artery can be performed successfully and effectively using the collateral channel.

Outcomes of First- Versus Second-Generation Drug-Eluting Stent Implanted for Right Coronary Artery Ostial Narrowing.

Clinical outcome is generally poor when stents are implanted at right coronary artery ostial lesion (RCAos). We compared the clinical outcome between the first-generation drug-eluting stent (first DES) and second-generation drug-eluting stent (second DES) used for RCAos. Consecutive 88 patients who underwent percutaneous coronary interventions of de novo RCAos using the first DES (33 patients) or second DES (55 patients) were analyzed. The incidence of major adverse cardiac events (MACE) defined as the composite of cardiac death, myocardial infarction attributed to right coronary artery, and target lesion revascularization within 2.5 years was compared. The incidence of MACE was significantly lower in second DES (11% vs 36%, p = 0.010) than that in the first DES. Multivariate analysis revealed use of second DES (odds ratio 0.24, 95% CI 0.11 to 0.93, p = 0.008) alone was significantly associated with MACE. In conclusion, second DES revealed better clinical outcome than the first DES when used in de novo RCAos.

Fibrillatory pattern of dissociated venous activity after pulmonary vein isolation: Novel characteristics for remnant foci of a trigger ectopy for atrial fibrillation.

BACKGROUND: Dissociated pulmonary vein activity (DPVA), defined as isolated intrinsic ectopic beats observed after successful pulmonary vein (PV) isolation, indicates the presence of remnant foci of trigger ectopy but has yet to be extensively studied. We investigated the correlation between DPVA and the PV triggers of atrial fibrillation (AF). METHOD AND RESULTS: Consecutive 110 patients undergoing AF ablation were enrolled. We defined trigger ectopy as documented ectopic foci observed to spontaneously initiate AF. Trigger ectopy was detected in 62 (56%) patients. DPVA in at least one PV was detected in 95 (86%) patients. Of the 440 isolated PVs, we recognized trigger ectopy in 73 (16%) PVs (culprit PVs) and DPVA in 184 (42%) PVs. DPVA was more frequently observed in culprit PVs than in non-culprit PVs [59% vs. 39%; odds ratio (OR)=2.3; p=0.001]. The concordance ratio of culprit PV was 67% (8/12) in PV with fibrillatory DPVA, 20% (35/172) in PV with non-fibrillatory DPVA, and 12% (30/256) in PV without DPVA. Fibrillatory DPVA was more frequently observed in culprit PVs than non-fibrillatory DPVA (OR=7.8; p=0.001). Non-PV foci were observed in 10 (11%) of the 95 patients with DPVA and 5 (33%) of the 15 patients without DPVA (OR=4.3; p=0.02). No significant difference in the frequency of AF recurrence was observed between them. CONCLUSIONS: Fibrillatory DPVA was found to be strongly associated with trigger ectopy of AF. Non-fibrillatory DPVA might merely indicate the existence of bystander ectopic foci located inside PVs. Non-PV ectopic foci were frequently observed in patients without DPVA.

Comparison of angioscopic findings among second-generation drug-eluting stents.

BACKGROUND: First-generation drug-eluting stents (DES) have reduced short-term stent failure as compared to bare-metal stents due to the inhibition of neointima hyperplasia, but instead increased the risk of very-late stent failure. Although better outcomes have been reported for second-generation DES than for first-generation DES, the difference in the angioscopic findings at 1-year follow-up has not been adequately elucidated among second-generation DES. METHODS: Consecutive 161 patients who received angioscopic examination at 1 year after implantation of second-generation DES, i.e. Nobori biolimus-eluting stents (Terumo, Tokyo, Japan) (N-BES, n=25), Xience everolimus-eluting stents (Abbot Vascular, Santa Clara, CA, USA; X-EES, n=95), or Resolute zotarolimus-eluting stents (Resolute Integrity; Medtronic, Minneapolis, MN, USA; R-ZES, n=41), in de novo native coronary lesions were analyzed. RESULTS: Maximum neointima coverage grade (N-BES, 0.9±0.3; X-EES, 1.2±0.4; R-ZES, 1.5±0.5; p<0.001) was the highest in R-ZES and lowest in N-BES. Heterogeneity score was higher in R-ZES than in N-BES (N-BES, 0.8±0.4; X-EES, 0.9±0.4; R-ZES, 1.1±0.5; p=0.007). Maximum yellow color grade and prevalence of thrombus were not different. Multivariate analysis demonstrated that only stent type was associated with maximum neointima coverage grade; stent type and total stent length were associated with heterogeneity score; and stenting for acute coronary syndrome (ACS) and total stent length were associated with maximum yellow color grade. CONCLUSIONS: Neointima coverage and heterogeneity were mainly determined by stent type even among second-generation DES, while yellow color was determined mainly by whether target lesion was of ACS.

Angioscopic Comparison of Resolute and Endeavor Zotarolimus-Eluting Stents.

BACKGROUND: Drug-eluting stents (DES) have reduced late loss and target lesion revascularization through the inhibition of neointimal hyperplasia, but instead increased the risk of very late stent failure due to incomplete neointimal coverage and neoatherosclerosis. Although newer DES are more effective and safer than the first-generation DES, the difference in the condition of the stented lesions between Resolute zotarolimus-eluting stents (R-ZES) and Endeavor zotarolimus-eluting stents (E-ZES) on angioscopy has not been reported. METHODS AND RESULTS: Consecutive patients who received R-ZES (n=46) or E-ZES (n=46) for de novo lesion of native coronary artery and had 1-year follow-up angioscopy were examined. Yellow color (grade 0-3), neointimal coverage (grade 0-2), heterogeneity score (maximum-minimum neointimal coverage grade) and thrombus (presence or absence) at stented lesion were evaluated. The maximum yellow color grade (1.2±0.9 vs. 0.7±1.0, P=0.005) was higher in R-ZES than in E-ZES. The maximum (1.9±0.3 vs. 1.5±0.5, P<0.001) and minimum (1.1±0.7 vs. 0.4±0.5, P<0.001) coverage grade was higher in E-ZES than in R-ZES. The heterogeneity score was higher in R-ZES than in E-ZES (1.0±0.5 vs. 0.7±0.7, P=0.007). Prevalence of thrombus was not different between the 2 stents (6.5% vs. 2.2%, P=0.4). CONCLUSIONS: E-ZES had better neointimal coverage with less yellow plaque and lower heterogeneity score than R-ZES. The lesions with E-ZES appeared more stable than those with R-ZES. (Circ J 2016; 80: 650-656).

In-Stent Yellow Plaque at 1 Year After Implantation Is Associated With Future Event of Very Late Stent Failure: The DESNOTE Study (Detect the Event of Very late Stent Failure From the Drug-Eluting Stent Not Well Covered by Neointima Determined by Angioscopy).

OBJECTIVES: This study examined whether coronary angioscopy-verified in-stent yellow plaque at 1 year after drug-eluting stent (DES) implantation is associated with future event of very late stent failure (VLSF). BACKGROUND: Atherosclerosis detected as yellow plaque by angioscopy has been associated with future events of acute coronary syndrome. Development of in-stent neoatherosclerosis is a probable mechanism of VLSF. METHODS: This study included 360 consecutive patients who received successful angioscopic examination at 1 year after implantation of a DES. They were clinically followed up for VLSF defined as cardiac death, acute myocardial infarction or unstable angina, or need for revascularization associated with the stent site. RESULTS: The follow-up interval was 1,558 ± 890 days (4.3 ± 2.4 years). The incidence of VLSF was significantly higher in the patients with yellow plaque than in those without (8.1% vs. 1.6%; log rank p = 0.02). Multivariable analysis revealed the presence of yellow plaque (hazard ratio [HR]: 5.38; p = 0.02) and absence of statin therapy (HR: 3.25; p = 0.02) as risks of VLSF. CONCLUSIONS: In-stent atherosclerosis evaluated by yellow plaque at 1 year after the implantation of DES and the absence of statin therapy were risks of VLSF. The underlying mechanism of VLSF appeared to be the progression of atherosclerosis as demonstrated by the yellow plaque.

Detection of yellow plaque by near-infrared spectroscopy - Comparison with coronary angioscopy in a case of no-flow phenomenon during coronary intervention.

Yellow plaques detected by coronary angioscopy have been regarded as vulnerable plaques and associated with distal embolization or slow/no-flow phenomenon during coronary intervention. This is the first report that compared the findings of angioscopy and near-infrared spectroscopy (NIRS) in a patient who suffered no-flow phenomenon during coronary intervention. A 41-year-old male patient with silent myocardial ischemia received coronary intervention. Coronary angiogram revealed diffuse stenosis in the distal right coronary artery. Target lesion was examined by NIRS and angioscopy. NIRS can detect lipid core plaque, which is presented as an yellow area in contrast to the normal red area. Target segment was filled with lipid core plaques. On the other hand, angioscopy revealed a ruptured yellow plaque with a thrombus in the target segment. The distribution of yellow plaques detected by angioscopy appeared well corresponded to the yellow areas detected by NIRS. After the insertion of filter-type distal protection device, balloon pre-dilatation and stent implantation were performed. Then, no-flow phenomenon occurred. Coronary flow was finally recovered in the protected vessel but was still disturbed in the non-protected vessel. The filter was filled with much plaque debris. The correlation between the yellow area detected by NIRS and the yellow plaques detected by angioscopy appeared very well. .