Elevated levels of plasma inactive stromal cell derived factor-1α predict poor long-term outcomes in diabetic patients following percutaneous coronary intervention.

BACKGROUND: Since the complication of diabetes mellitus (DM) is a risk for adverse cardiovascular outcomes in patients with coronary artery disease (CAD), appropriate risk estimation is needed in diabetic patients following percutaneous coronary intervention (PCI). However, there is no useful biomarker to predict outcomes in this population. Although stromal cell derived factor-1α (SDF-1α), a circulating chemokine, was shown to have cardioprotective roles, the prognostic impact of SDF-1α in diabetic patients with CAD is yet to be fully elucidated. Moreover, roles of SDF-1α isoforms in outcome prediction remain unclear. Therefore, this study aimed to assess the prognostic implication of three forms of SDF-1α including total, active, and inactive forms of SDF-1α in patients with DM and after PCI. METHODS: This single-center retrospective analysis involved consecutive patients with diabetes who underwent PCI for the first time between 2008 and 2018 (n = 849). Primary and secondary outcome measures were all-cause death and the composite of cardiovascular death, non-fatal myocardial infarction, and ischemic stroke (3P-MACE), respectively. For determining plasma levels of SDF-1α, we measured not only total, but also the active type of SDF-1α by ELISA. Inactive isoform of the SDF-1α was calculated by subtracting the active isoform from total SDF-1α. RESULTS: Unadjusted Kaplan-Meier analyses revealed increased risk of both all-cause death and 3P-MACE in patients with elevated levels of inactive SDF-1α. However, plasma levels of total and active SDF-1α were not associated with cumulative incidences of outcome measures. Multivariate Cox hazard analyses repeatedly indicated the 1 higher log-transformed inactive SDF-1α was significantly associated with increased risk of all-cause death (hazard ratio (HR): 2.64, 95% confidence interval (CI): 1.28-5.34, p = 0.008) and 3P-MACE (HR: 2.51, 95% CI: 1.12-5.46, p = 0.02). Moreover, the predictive performance of inactive SDF-1α was higher than that of total SDF-1α (C-statistics of inactive and total SDF-1α for all-cause death: 0.631 vs 0.554, for 3P-MACE: 0.623 vs 0.524, respectively). CONCLUSION: The study results indicate that elevated levels of plasma inactive SDF-1α might be a useful indicator of poor long-term outcomes in diabetic patients following PCI. TRIAL REGISTRATION: This study describes a retrospective analysis of a prospective registry database of patients who underwent PCI at Juntendo University Hospital, Tokyo, Japan (Juntendo Physicians' Alliance for Clinical Trials, J-PACT), which is publicly registered (University Medical Information Network Japan-Clinical Trials Registry, UMIN-CTR 000035587).

Impact of Low-Dose Prasugrel on Platelet Reactivity in Chronic Phase of Post-Percutaneous Coronary Intervention (CHAPERON): a Prospective Cohort Study.

PURPOSE: Asians often face the problems of clopidogrel resistance and East Asian paradox. This study aimed to evaluate the effects of P2Y12 inhibitors, including low-dose prasugrel 2.5 mg, on the P2Y12 reaction unit (PRU) in the chronic phase after percutaneous coronary intervention (PCI). METHODS: A total of 348 patients were studied. PRU was measured 6-12 months after PCI and subsequently, 6 months later using a P2Y12 assay, respectively. This study evaluated the proportion of bleeding risk (PRU ≤ 85) and ischemic risk (PRU ≥ 239) as primary endpoints, and the prediction of bleeding risk and ischemic risk using multivariable logistic regression analysis. RESULTS: At baseline, 136 patients (39%) received prasugrel 3.75 mg, 48 patients (14%) received prasugrel 2.5 mg, and 164 patients (47%) received clopidogrel 75 mg. Clopidogrel 75 mg had a significantly higher proportion of ischemic risk within one year after PCI than the other groups, and was an independent predictor for ischemic risk with reference of prasugrel 3.75 mg. In addition, switching from clopidogrel 75 mg to prasugrel 2.5 mg significantly lowered and aggregated the PRU value. Whereas, dose reduction of prasugrel had a significantly lower proportion of bleeding risk over one year after PCI than the continuation of prasugrel 3.75 mg, and was an independent predictor for bleeding risk with reference of continuation of prasugrel 3.75 mg. CONCLUSIONS: Prasugrel 2.5 mg has a lower ischemic risk and a more stable PRU value compared with clopidogrel treatment. Prasugrel also contributes to a decline in bleeding risk with concomitant dose reduction. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN), ID: UMIN000029541, Date: October 16, 2017 ( https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000033395 ).

A case report of pulmonary artery intimal sarcoma negative for 18F-FDG mimicking pulmonary thromboembolism.

Background: Pulmonary artery sarcoma is a rare malignant neoplasm arising from intimal mesenchymal cells in the pulmonary artery wall and is often difficult to differentiate from pulmonary embolism, however, 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) can be useful for a differential diagnosis. Here, we present a rare case of pulmonary sarcoma undetectable by PET. Case summary: A 77-year-old woman who had worsening dyspnoea on effort for a month and progressive chest discomfort with nocturnal cough for a week presented to our hospital. Contrast-enhanced computed tomography (CT) demonstrated a massive filling defect in the left pulmonary artery (PA). Two major differential diagnoses were considered; pulmonary thromboembolism and tumour-like lesions. Positron emission tomography-computed tomography (PET-CT) revealed that there was no abnormal accumulation of 18F-FDG in the mass. However, even after effective anti-thrombotic treatment for 3 weeks, a follow-up CT showed no reduction at all in the size of the lesion in the pulmonary artery. Therefore, surgery for diagnostic therapeutic purposes was performed. Discussion: The present case is informative because it supports the idea that being aware of PA angiosarcoma as a potential differential diagnosis of pulmonary thromboembolism is essential, particularly in cases of no evident peripheral venous thrombosis and a negative D-dimer test, even if neither heterogenous contrast enhancement in CT and magnetic resonance imaging nor accumulation of 18-FDG in PET-CT is evident.

Favorable Prognosis in Patients with Recovered Pulmonary Hypertension after TAVI: An Analysis of the LAPLACE-TAVI Registry.

Pulmonary hypertension (PH) is a common complication of aortic stenosis (AS). Despite the established association between PH and poor outcomes in patients with AS, the prognostic implication of a change in PH after transcatheter aortic valve implantation (TAVI) has been rarely evaluated. This study analyzed a prospective multi-center TAVI registry database involving six Japanese centers and used the transtricuspid pressure gradient (TRPG) obtained by echocardiography to estimate pulmonary artery systolic pressure. The participants (n = 2056) were first divided into two groups by TRPG before TAVI, a PH (−) group (TRPG < 30 mmHg) (n = 1407, 61.9%) and a PH (+) group (TRPG ≥ 30 mmHg) (n = 649, 28.6%). Next, by TRPG after (4.1 ± 5.3 days) TAVI, the PH (+) group was further subdivided into two groups, Recovered PH (TRPG < 30 mmHg, n = 253) and Persistent PH (TRPG after TAVI ≥ 30 mmHg, n = 396). The median follow-up duration was 1.8 years. The primary and secondary endpoints were the composite and each of cardiovascular (CV) death and heart failure hospitalization, respectively. Unadjusted Kaplan-Meier estimates with log-rank comparisons showed significantly higher cumulative incidences of primary and secondary endpoints in the Persistent PH group compared to other groups. Moreover, adjusted multivariate Cox-proportional hazard analyses showed that a decreased (−10 mmHg) TRPG after TAVI was linearly associated with a reduced risk of the primary endpoint (hazard ratio (HR): 0.76, 95% confidence interval (CI): 0.64−0.90, p = 0.0020). The findings in the present study indicate that the recovery of PH may partly contributes to the prognostic benefit of TAVI procedure in patients with AS and elevated pulmonary artery systolic pressure.

Atypical Shone's Complex Diagnosed at 70 Years Old: Presenting with Double-orifice Mitral Valve, Bicuspid Aortic Valve, and Aortic Coarctation.

Atypical Shone's complex is a rare congenital anomaly involving a left-sided obstructive lesion of two or three cardiovascular levels. A 70-year-old man with dyspnea on exertion was diagnosed with severe aortic stenosis (AS) with a bicuspid valve, complicated by severe aortic coarctation (CoA) and a double-orifice mitral valve. He underwent surgery for AS and CoA in one session. It is important to search for complicated malformations, even in cases of bicuspid aortic valve found in old age.

Dipeptidyl peptidase-4 inhibitors reduced long-term cardiovascular risk in diabetic patients after percutaneous coronary intervention via insulin-like growth factor-1 axis.

Dipeptidyl-peptidase-4 inhibitors (DPP4i) have been the most used antidiabetic medications worldwide due to their good safety profiles and tolerability with a low risk of hypoglycemia, however, large cardiovascular outcome trials (CVOTs) have not shown any significant the prognostic superiority. On the contrary, since observational studies have suggested the effects of DPP4i are enhanced some populations, such as Asians and those who without overweight, their prognostic benefit is still under debate. The aim of this study was thus to assess the prognostic impact of DPP4i in patients with both diabetes and coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI) through the insulin-like growth factor-1 (IGF-1) axis, a substrate of DPP4. This single-center analysis involved consecutive Japanese diabetic patients who underwent PCI for the first time between 2008 and 2018 (n = 885). Primary and secondary endpoints were set as cardiovascular (CV) death and the composite of CV death, non-fatal myocardial infarction and ischemic stroke (3P-MACE). Serum levels of IGF-1 and its main binding protein (insulin-like growth factor binding protein-3: IGFBP-3) were measured. In consequences, unadjusted Kaplan-Meier analyses revealed reduced incidences of CV-death and 3P-MACE by DPP4i, which was particularly enhanced in patients who were not overweight (BMI ≤ 25). Multivariate Cox hazard analyses consistently indicated reduced risks of CV death by DPP4i at PCI (hazard ratio (HR) 0.39, 95% confidence interval (CI) 0.16-0.82, p = 0.01) and 3P-MACE (HR 0.47, 95% CI 0.25-0.84, p = 0.01), respectively. Moreover, elevated IGF-1 activity indicated by the IGF-1/IGFBP-3 ratio was associated with decreased risks of both endpoints and it was significantly higher in patients with DPP4i (p < 0.0001). In conclusion, the findings of the present study indicate beneficial effects of DPP4i to improve outcomes in Japanese diabetic patients following PCI, which might be mediated by DPP4-IGF-1 axis.

Long-term impact of ß-blocker in elderly patients without myocardial infarction after percutaneous coronary intervention.

AIMS: Little is known about the long-term outcomes of ß-blockers use in patients with coronary artery disease (CAD) without myocardial infarction (MI) and reduced ejection fraction (rEF). However, more attention should be paid to the oral administration of ß-blockers in elderly patients who are susceptible to heart failure (HF), sinus node dysfunction, or rate response insufficiency. We aimed to evaluate the long-term impact of ß-blockers in elderly patients with CAD without MI or systolic HF who have undergone percutaneous coronary intervention. METHODS AND RESULTS: A total of 1018 consecutive elderly patients with CAD (mean age, 72 ± 7 years; 77% men) who underwent their first intervention between 2010 and 2018 were included in this study. According to the presence or absence of the use of ß-blockers, 514 patients (50.5%) were allocated to the ß-blocker group, and 504 (49.5%) to the non-ß-blocker group. We evaluated the incidence of 4-point major adverse cardiovascular events (4P-MACE), including cardiovascular death, non-fatal MI, non-fatal stroke, admission for HF, target vessel revascularization (TVR), and all-cause death. We focused on the association between chronotropic incompetence of ß-blockers and incidence of a new HF and analysed the results using an exercise electrocardiogram regularly performed in the outpatient department after percutaneous coronary intervention. During a median follow-up duration of 5.1 years, 83 patients (8.3%) developed 4P-MACE, including cardiovascular death in 17, non-fatal MI in 13, non-fatal stroke in 25, and admission for HF in 39 patients. Additionally, 124 patients (12.2%) had a TVR and 104 (10.2%) died of other causes. Kaplan-Meier analysis showed that the cumulative incidence rate of 4P-MACE in the ß-blocker group was significantly higher than that in the non-ß-blocker group (15.4% vs. 10.0%, log-rank test, P = 0.015). Above all, the cumulative incidence rate of admission for HF in the ß-blocker group was significantly higher (8.8% vs. 3.2%, log-rank test, P < 0.001). The ß-blocker group had significantly lower resting heart rate, stress heart rate, and stress-rest Δ heart rate on exercise electrocardiogram. Multivariate Cox hazard analysis revealed that EF, ß-blocker use, stress-rest Δ heart rate, and CKD were strong independent predictors of admission for HF. CONCLUSIONS: Long-term ß-blocker use was significantly associated with an increased risk of adverse cardiovascular events in elderly patients with CAD without MI or systolic HF. In particular, the chronotropic incompetence action of ß-blockers could increase the risk of admission for HF in elderly patients with CAD without MI and systolic HF, and the present findings warrant further investigation.