Clinical features, future cardiac events, and prognostic factors following percutaneous coronary intervention in young female patients.

BACKGROUND: The proportion of young females among the patients who undergo percutaneous coronary intervention (PCI) is relatively small, and information on their clinical characteristics is limited. This study investigated the clinical characteristics and prognostic factors for future cardiac events in young females who underwent PCI. METHODS: This multicenter observational study included 187 consecutive female patients aged < 60 years who underwent PCI in seven hospitals. The primary composite endpoint was the incidence of cardiac death, nonfatal myocardial infarction, and target vessel revascularization. RESULTS: The mean patient age was 52.1 ± 6.1 years and 89 (47.6%) had diabetes, and renal dysfunction (an estimated glomerular filtration rate < 60 mL/min/1.73 m2) was observed in 38 (20.3%). During a median follow-up of 3.3 years, the primary endpoint occurred in 28 patients. The Cox proportional hazards models showed that renal dysfunction was an independent predictor for the primary endpoint (hazard ratio 3.04, 95% confidence interval 1.25-7.40, p = 0.01), as well as multivessel disease (hazard ratio 2.79, 95% confidence interval 1.12-6.93, p = 0.03). Patients with renal dysfunction had a significantly higher risk for the primary endpoint than those without renal dysfunction. CONCLUSIONS: Renal dysfunction was strongly associated with future cardiac events in young females who underwent PCI.

Long-term outcomes of percutaneous revascularization for internal mammary artery-left anterior descending artery bypass failure.

Despite the excellent long-term results of internal mammary artery (IMA)-left anterior descending (LAD) bypass, percutaneous revascularization of IMA is sometimes required for IMA-LAD bypass failure. However, its clinical outcomes have not been fully elucidated. The aim of this study was to investigate the long-term clinical outcomes, including target lesion revascularization (TLR) following contemporary percutaneous revascularization of failed IMA bypass graft. We examined data of 59 patients who had undergone percutaneous revascularization of IMA due to IMA-LAD bypass failure at nine hospitals. Patients with IMA graft used for Y-composite graft or sequential bypass graft were excluded. The incidence of TLR was primarily examined, whereas other clinical outcomes including cardiac death, myocardial infarction, and target vessel revascularization were also evaluated. Mean age of the enrolled patients was 67.4 ± 11.3 years, and 74.6% were men. Forty patients (67.8%) had anastomotic lesions, and 17 (28.8%) underwent revascularization within three months after bypass surgery. Procedural success was achieved in 55 (93.2%) patients. Stent implantation was performed in 13 patients (22.0%). During a median follow-up of 1401 days (interquartile range, 282-2521 days), TLR was required in six patients (8.5% at 1, 3, and 5 years). Patients who underwent percutaneous revascularization within 3 months after surgery tended to have a higher incidence of TLR. Clinical outcomes of IMA revascularization for IMA-LAD bypass failure were acceptable.

Comparison of the empirical linear ablation and low voltage area-guided ablation in addition to pulmonary vein isolation in patients with persistent atrial fibrillation: a propensity score-matched analysis.

BACKGROUND: The efficacy of pulmonary vein isolation (PVI) alone is not guaranteed for persistent atrial fibrillation (PeAF), and it is unclear which type of ablation approach should be applied in addition to PVI. This study aimed to compare outcomes and prognosis between empirical linear ablation and low-voltage area (LVA) ablation after PVI for PeAF. METHODS: We enrolled 128 patients with PeAF who were assigned to the linear ablation group (n = 64) and the LVA ablation group (n = 64) using a propensity score-matched model. After PVI and cardioversion, the patients underwent either empirical linear ablation or LVA ablation during sinus rhythm. All patients in the linear ablation group underwent both roof line and mitral valve isthmus (MVI) ablations. An electrical-guided ablation targeting LVA (< 0.5 mV) was performed in the LVA group. When there was no LVA in the LVA group, only PVI was applied. We compared the procedural outcomes and recurrence after ablation between the two groups. RESULTS: The baseline characteristics were well-balanced between the two groups. Fifty patients had LVA (22 and 28 patients in the linear and LVA groups). The roof and MVI lines were completed in 100% and 96.9% of the patients. During the mean follow-up of 279.5 ± 161.3 days, the LVA group had significantly lower recurrence than the linear group (15 patients [23%] vs. 29 patients [45%], p = 0.014). Thirty-five patients were prescribed antiarrhythmic drugs during the follow-up period (linear group, n = 17; LVA group, n = 18); amiodarone and bepridil were administered to most of the patients (15 and 17 patients, respectively). The difference in the prognosis was relevant among the patients with LVA, while this trend was not observed in those without LVA. The LVA ablation group demonstrated significantly lower radiofrequency energy and shorter procedural time compared to the linear ablation group. The recurrence of atrial flutter was more likely to occur in the linear group than in the LVA group (14 [22%] vs. 6 [9.4%], p = 0.052). CONCLUSION: The electrophysiological-guided LVA ablation is more effective than empirical linear ablation in PeAF patients with LVA. Unnecessary empirical linear ablation might have a risk of iatrogenic gap and atrial flutter recurrence.

Clinical characteristics and treatment of Spontaneous Coronary Artery Dissection in Young Women Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) has recently been recognized as a cause of acute coronary syndrome (ACS), especially in young women. However, the characteristics, optimal treatment, and prognosis of patients who experience SCAD have not been fully described. METHODS: Data were retrospectively collected from a multicenter registry. Among 187 young women less than 60 years of age who underwent percutaneous coronary intervention, 19 (10.2%) with SCAD were identified through coronary angiography. Clinical characteristics and outcomes were investigated. RESULTS: Those with SCAD less frequently exhibited coronary risk factors, such as diabetes, dyslipidemia, and smoking, than those without SCAD. Intense emotional and/or physical stress was more frequently observed as a prominent precipitating factor in cases of SCAD. All 19 SCAD patients presented with ACS, 7 of whom were treated using stents, and the other 12 treated without stents. During a median follow-up of 960 days (interquartile range, 686-1504 days), two recurrent coronary artery dissections occurred within 7 days, both of which occurred in a vessel other than that in which primary dissection occurred. There were no deaths or recurrent dissection after 1 week. CONCLUSION: SCAD was not uncommon among young Japanese women requiring percutaneous coronary intervention. Patients with SCAD exhibited fewer coronary risk factors and more precipitating factors than those without SCAD, and long-term clinical outcomes after an early period appeared to be favorable.

Adiponectin ameliorates doxorubicin-induced cardiotoxicity through Akt protein-dependent mechanism.

Accumulating evidence shows that obesity is associated with doxorubicin cardiac toxicity in the heart, but the molecular mechanisms that contribute to this pathological response are not understood. Adiponectin is an adipose-derived, cardioprotective factor that is down-regulated in obesity. Here, we investigated the effect of adiponectin on doxorubicin (DOX)-induced cardiotoxicity and assessed the mechanisms of this effect. A single dose of DOX was intraperitoneally injected into the abdomen of adiponectin knock-out (APN-KO) and wild-type (WT) mice. APN-KO mice had increased mortality and exacerbated contractile dysfunction of left ventricle compared with WT mice. APN-KO mice also showed increased apoptotic activity and diminished Akt signaling in the failing myocardium. Systemic delivery of adenoviral vector expressing adiponectin improved left ventricle dysfunction and myocardial apoptosis following DOX injection in WT and APN-KO mice but not in Akt1 heterozygous KO mice. In cultured rat neonatal cardiomyocytes, adiponectin stimulated Akt phosphorylation and inhibited DOX-stimulated apoptosis. Treatment with sphingosine kinase-1 inhibitor or sphingosine 1-phosphate receptor antagonist diminished adiponectin-induced Akt phosphorylation and reversed the inhibitory effects of adiponectin on myocyte apoptosis. Pretreatment with anti-calreticulin antibody reduced the binding of adiponectin to cardiac myocytes and blocked the adiponectin-stimulated increase in Akt activation and survival in cardiomyocytes. Interference of the LRP1/calreticulin co-receptor system by siRNA or blocking antibodies diminished the stimulatory actions of adiponectin on Akt activation and myocyte survival. These data show that adiponectin protects against DOX-induced cardiotoxicity by its ability to promote Akt signaling.

Caloric restriction stimulates revascularization in response to ischemia via adiponectin-mediated activation of endothelial nitric-oxide synthase.

Caloric restriction (CR) can extend longevity and modulate the features of obesity-related metabolic and vascular diseases. However, the functional roles of CR in regulation of revascularization in response to ischemia have not been examined. Here we investigated whether CR modulates vascular response by employing a murine hindlimb ischemia model. Wild-type (WT) mice were randomly divided into two groups that were fed either ad libitum (AL) or CR (65% of the diet consumption of AL). Four weeks later, mice were subjected to unilateral hindlimb ischemic surgery. Body weight of WT mice fed CR (CR-WT) was decreased by 26% compared with WT mice fed AL (AL-WT). Revascularization of ischemic hindlimb relative to the contralateral limb was accelerated in CR-WT compared with AL-WT as evaluated by laser Doppler blood flow and capillary density analyses. CR-WT mice had significantly higher plasma levels of the fat-derived hormone adiponectin compared with AL-WT mice. In contrast to WT mice, CR did not affect the revascularization of ischemic limbs of adiponectin-deficient (APN-KO) mice. CR stimulated the phosphorylation of endothelial nitric-oxide synthase (eNOS) in the ischemic limbs of WT mice. CR increased plasma adiponectin levels in eNOS-KO mice but did not stimulate limb perfusion in this strain. CR-WT mice showed enhanced phosphorylation of AMP-activated protein kinase (AMPK) in ischemic muscle, and administration of AMPK inhibitor compound C abolished CR-induced increase in limb perfusion and eNOS phosphorylation in WT mice. Our observations indicate that CR can promote revascularization in response to tissue ischemia via an AMPK-eNOS-dependent mechanism that is mediated by adiponectin.

Adiponectin promotes endothelial progenitor cell number and function.

Obesity-linked diseases are associated with suppressed endothelial progenitor cell (EPC) function. Adiponectin is an adipose-derived protein that is downregulated in obese and diabetic subjects. Here, we investigated the effects of adiponectin on EPCs. EPC levels did not increase in adiponectin deficient (APN-KO) in response to hindlimb ischemia. Adenovirus-mediated delivery of adiponectin increased EPC levels in both WT and APN-KO mice. Incubation of human peripheral blood mononuclear cells with adiponectin led to an increase of the number of EPCs. Adiponectin induced EPC differentiation into network structures and served as a chemoattractant in EPC migration assays. These data suggest that hypoadiponectinemia may contribute to the depression of EPC levels that are observed in patients with obesity-related cardiovascular disorders.