Prognostic Impact of Peak Aortic Jet Velocity on Patients With Acute Myocardial Infarction.

BACKGROUND: Aortic valve stenosis (AS) leads to increased cardiovascular mortality and morbidity, and recent studies reported that even mild-to-moderate AS was associated with poor prognosis in the general population. This study investigated the prognostic impact of mild or moderate AS, defined as 2.0 m/s ≤ peak aortic jet velocity (Vmax) ≤3.9 m/s using echocardiography in acute myocardial infarction (AMI) patients.Methods and Results: This study enrolled 3,049 AMI patients using data from the Mie ACS registry. Patients were divided into 2 groups according to Vmax: Group 1: Vmax <2.0 m/s and/or visually intact aortic valve in which all 3 leaflets are fully and evenly open; Group 2: 2.0 m/s ≤ Vmax ≤ 3.9 m/s. There were 2,976 patients in Group 1and 73 patients in Group 2. The Group 2 patients were older, had a higher percentage of males and had lower body mass index and Killip ≥2 than the Group 1 patients. Angiographic data, door-to-balloon time, and mechanical support were not different between the 2 groups. The Group 2 patients demonstrated a significantly higher all-cause mortality rate (P<0.01) and composite of cardiovascular death and heart failure hospitalization (P<0.01), and Kaplan-Meier analysis showed the same tendency in propensity score-matched patients. CONCLUSIONS: The present study revealed that mild or moderate AS based on Vmax is associated with poor prognosis following AMI.

Effects of sitagliptin on exercise capacity and hemodynamics in patients with type 2 diabetes mellitus and coronary artery disease.

Sitagliptin attenuates left ventricular (LV) dysfunction and may improve oxygen uptake in animals. The effects of sitagliptin on oxygen uptake (VO2) and exercise hemodynamics have been unclear in patients with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD). Thirty patients with T2DM and CAD were randomized into a sitagliptin (50 mg/day) or voglibose (0.6 mg/day) group. Patients underwent maximal cardiopulmonary exercise testing. VO2 and hemodynamics were evaluated at rest, anaerobic threshold and peak exercise. Resting LV diastolic function (E', peak early diastolic mitral annular velocity) and geometry were evaluated by echocardiography, and endothelial function by reactive hyperemia peripheral arterial tonometry. A total of 24 patients (69 ± 9 years) completed 6 months of intervention. Peak VO2 in the sitagliptin and voglibose groups (25.3 ± 7.3 vs. 24.0 ± 7.4, 22.7 ± 4.8 vs. 22.1 ± 5.2 ml/kg/min) was slightly decreased after 6 months (time effect p = 0.051; group × time effect p = 0.49). No effects were observed on LV ejection fraction, E', or reactive hyperemia index in either group. Heart rate during exercise was unaffected in both groups. Systolic blood pressure was unchanged by sitagliptin at rest and during exercise, but slightly lowered by voglibose at anaerobic threshold and peak exercise. In patients with T2DM and CAD, sitagliptin had little effect on resting LV and arterial function, exercise capacity, or exercise hemodynamics. Further studies need to be conducted with more patients as the number of the patients in this study was limited.

Effect of Sitagliptin on Coronary Flow Reserve Assessed by Magnetic Resonance Imaging in Type 2 Diabetic Patients With Coronary Artery Disease.

BACKGROUND: The present study was conducted to assess the cardiovascular effects of dipeptidyl peptidase-4 inhibitors (DPP4i) on coronary flow reserve (CFR), left ventricular (LV) function and endothelial function of the peripheral artery by comparison with those of α-glucosidase inhibitors (αGI) in patients with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD).Methods and Results:We randomly assigned 30 patients with T2DM and CAD to receive either sitagliptin or voglibose, and 28 patients (age 69±9 years, 75% male, hemoglobin A1c [HbA1c] 6.62±0.48%) completed the study (14 in each group). CFR and LV function, assessed by cardiac magnetic resonance imaging, and endothelial function, assessed by reactive hyperemia peripheral arterial tonometry (RH-PAT), were measured at baseline and 24 weeks after treatment. Clinical and laboratory parameters, including HbA1c level, plasma active glucagon-like peptide-1 concentrations, and biomarkers of inflammation, were unchanged in both groups after 24 weeks of treatment. CFR were unchanged in both the αGI group (3.01±0.98 at baseline and 3.06±0.8 after treatment, P=NS) and the DPP4i group (4.29±2.04 at baseline and 3.63±1.31 after treatment, P=NS), with no interaction effect. LV functional parameters and the reactive hyperemia index also remained unchanged after the 24-week treatment. CONCLUSIONS: DPP4i did not improve CFR, LV function or endothelial function of the peripheral artery in patients with relatively well-controlled T2DM and CAD.

A Survival Case of Fulminant Right-Side Dominant Eosinophilic Myocarditis.

A 59-year-old Japanese woman was admitted to a nearby hospital with dyspnea and general malaise. Transthoracic echocardiography revealed right ventricular (RV) dilatation with severely reduced systolic function and leftward shift of the intraventricular septum. She was initially diagnosed with acute right heart failure, and fell into cardiogenic shock requiring an intra-aortic balloon pump and inotropic agents. An endomyocardial biopsy (EMB) demonstrated extensive interstitial edema, infiltration of inflammatory cells including numerous eosinophils, and myocytolysis with eosinophil degranulation. She was histologically diagnosed with eosinophilic myocarditis. Steroid pulse therapy was initiated, and her hemodynamic status improved along with dramatic recovery of the RV function. EMB 6 days after the initiation of steroid pulse therapy showed the disappearance of infiltration and degranulation of eosinophils, although lymphocytic infiltration still remained. Positron emission tomography-computed tomography (PET/CT) 23 days after steroid pulse therapy showed an increased 18F-FDG uptake in the intraventricular septum and left ventricle, suggesting persistent myocardial inflammation. She was then treated with a maintenance dose of prednisolone. She became free of symptoms and follow-up echocardiography showed normal cardiac function 3 months after the initiation of corticosteroid treatment. In addition, EMB and PET/CT showed no inflammation. This is the first case report of fulminant and right-sided dominant eosinophilic myocarditis successfully treated with corticosteroid.

Effect of combination therapy of ezetimibe and rosuvastatin on regression of coronary atherosclerosis in patients with coronary artery disease.

Ezetimibe has been reported to provide significant incremental reduction in low-density-lipoprotein cholesterol (LDL-C) when added to a statin; however, its effect on coronary atherosclerosis has not yet been evaluated in detail. The aim of this study was to investigate the add-on effect of ezetimibe to a statin on coronary atherosclerosis evaluated by intravascular ultrasound (IVUS).In this prospective randomized open-label study, a total of 51 patients with stable coronary artery disease (CAD) requiring percutaneous coronary intervention (PCI) were enrolled, and assigned to a combination group (n = 26, rosuvastatin 5 mg/day + ezetimibe 10 mg/day) or a monotherapy group (n = 25, rosuvastatin 5 mg/day). Volumetric IVUS analyses were performed at baseline and 6 months after the treatment for a non-PCI site. LDL-C level was significantly reduced in the combination group (-55.8%) versus that in the monotherapy group (-36.8%; P = 0.004). The percent change in plaque volume (PV), the primary endpoint, appeared to decrease more effectively in the combination group compared with the monotherapy group (-13.2% versus -3.1%, respectively, P = 0.050). Moreover, there was a significant group × time interaction in the effects of the two treatments on PV (P = 0.021), indicating the regressive effect of the combination therapy on PV was greater than that of monotherapy for subtly different values of baseline PV in the two treatment groups. Moreover, percent change in PV showed positive correlations with percent change of LDL-C (r = 0.384, P = 0.015).Intensive lipid-lowering therapy with ezetimibe added to usual-dose statin may provide significant incremental reduction in coronary plaques compared with usual-dose statin monotherapy.

Effect of left ventricular ejection fraction on the prognostic impact of chronic total occlusion in a non-infarct-related artery in patients with acute myocardial infarction.

BACKGROUND: Chronic total occlusion (CTO) in a non-infarct-related artery (IRA) in patients with acute coronary syndrome (ACS) is associated with a poor prognosis. However, whether the prognostic impact of non-IRA CTO differs according to left ventricular ejection fraction (LVEF) is unclear. METHODS AND RESULTS: A total of 2060 consecutive acute myocardial infarction (AMI) patients who underwent primary percutaneous coronary intervention (PCI) were classified into 2 groups according to their LVEF (reduced EF: LVEF < 50%, preserved EF: LVEF ≥ 50%) and further subdivided according to the presence of concomitant non-IRA CTO. In the reduced EF group, patients with CTO had a higher 1-year all-cause death rate (20.3% vs. 34.3%, P = 0.001) and major adverse cardiac event rate (MACE: 19.6% vs. 39.6%, P < 0.001) compared to those without CTO, but they were similar between patients with and without CTO in the preserved EF group. Non-IRA CTO was an independent predictor of all-cause death (HR 1.58, 95% CI 1.06-2.33, P = 0.02) and MACE (HR 1.67, 95% CI 1.14-2.46, P = 0.009) only in the reduced EF group. In addition, the outcomes of successful CTO-PCI seemed to be similar to those without CTO in the reduced EF group. CONCLUSIONS: CTO in a non-IRA may contribute to a poor prognosis only in AMI patients with reduced LVEF.

Multiple Life-threatening Coronary Artery Spasms after Percutaneous Coronary Intervention for Acute Coronary Syndrome.

A 69-year-old man who had been hospitalized with acute coronary syndrome (ACS), underwent urgent percutaneous coronary intervention. In the subacute phase, he developed sudden chest pain and hemodynamic deterioration, and urgent coronary angiogram showed multiple coronary artery spasms. The discontinuation of beta-blocker treatment and the administration of a calcium antagonist helped prevent angina attacks. In Japanese patients who tend to have coronary artery spasm, the routine administration of beta-blockers for post-ACS patients with a preserved left ventricular systolic function should be considered carefully.

Possible involvement of dynorphin A release via mu1-opioid receptor on supraspinal antinociception of endomorphin-2.

It has been demonstrated that the antinociception induced by i.t. or i.c.v. administration of endomorphins is mediated through mu-opioid receptors. Moreover, though endomorphins do not have appreciable affinity for kappa-opioid receptors, pretreatment with the kappa-opioid receptor antagonist nor-binaltorphimine markedly blocks the antinociception induced by i.c.v.- or i.t.-injected endomorphin-2, but not endomorphin-1. These evidences propose the hypothesis that endomorphin-2 may initially stimulate the mu-opioid receptors, which subsequently induces the release of dynorphins acting on kappa-opioid receptors to produce antinociception. The present study was performed to determine whether the release of dynorphins by i.c.v.-administered endomorphin-2 is mediated through mu-opioid receptors for producing antinociception. Intracerebroventricular pretreatment with an antiserum against dynorphin A, but not dynorphin B or alpha-neo-endorphin, and s.c. pretreatment with kappa-opioid receptor antagonist nor-binaltorphimine dose-dependently attenuated the antinociception induced by i.c.v.-administered endomorphin-2, but not endomorphin-1 and DAMGO. The attenuation of endomorphin-2-induced antinociception by pretreatment with antiserum against dynorphin A or nor-binaltorphimine was dose-dependently eliminated by additional s.c. pretreatment with a selective mu-opioid receptor antagonist beta-funaltrexamine or a selective mu1-opioid receptor antagonist naloxonazine at ultra low doses, which are inactive against micro-opioid receptor agonists in antinociception, suggesting that endomorphin-2 stimulates distinct subclass of micro1-opioid receptor that induces the release of dynorphin A acting on kappa-opioid receptors in the brain. It concludes that the antinociception induced by supraspinally administered endomorphin-2 is in part mediated through the release of endogenous kappa-opioid peptide dynorphin A, which is caused by the stimulation of distinct subclass of micro1-opioid receptor.

Trousseau's Syndrome Causing Refractory Deep Venous Thrombosis.

A 66-year-old man, who had been diagnosed with deep venous thrombosis (DVT), and who was treated with a vitamin K antagonist (VKA) and who had undergone the implantation of an inferior vena cava filter, was admitted due to an exacerbation of DVT. VKA was administered again; however, the patient's DVT worsened. Further examinations revealed colon cancer, which led to a diagnosis of Trousseau's syndrome. The regression of the thrombi was confirmed after the administration of heparin and the resection of the tumors. Trousseau's syndrome should always be kept in mind when patients present with refractory venous thrombosis. The administration of heparin, and cancer control are necessary for the effective treatment of thrombosis in such cases.

Combined Assessment of Stress Myocardial Perfusion Cardiovascular Magnetic Resonance and Flow Measurement in the Coronary Sinus Improves Prediction of Functionally Significant Coronary Stenosis Determined by Fractional Flow Reserve in Multivessel Disease.

BACKGROUND: Recent studies using stress-rest perfusion cardiovascular magnetic resonance (CMR) demonstrated a close correlation between myocardial ischemia and reduced fractional flow reserve (FFR). However, its diagnostic concordance may be reduced in patients with multivessel disease. We sought to evaluate the concordance of adenosine stress-rest perfusion CMR for predicting reduced FFR, and to determine the additive value of measuring global coronary flow reserve (CFR) in the coronary sinus in multivessel disease. METHODS AND RESULTS: Ninety-six patients with angiographic luminal narrowing >50% underwent comprehensive CMR study and FFR measurements in 139 coronary vessels. FFR <0.80 was considered hemodynamically significant. Global CFR was quantified as the ratio of stress-rest coronary sinus flow measured by phase-contrast cine CMR. In 25 patients with single-vessel disease, visual assessment of perfusion CMR yielded high diagnostic concordance for predicting flow-limiting stenosis, with the area under receiver operating characteristic curve of 0.93 on a per-patient basis. However, in 71 patients with multivessel disease, perfusion CMR underestimated flow-limiting stenosis, resulting in the reduced area under receiver operating characteristic curve of 0.74. When CFR of <2.0 measured in the coronary sinus was considered as global myocardial ischemia, combined assessment provided correct reclassifications in 7 patients with false-negative myocardial ischemia, and improved the diagnostic concordance to 92% sensitivity and 73% specificity with the area under receiver operating characteristic curve of 0.88 (95% confidence interval, 0.80%-0.97%, P=0.002). CONCLUSIONS: Visual analysis of stress-rest perfusion CMR has limited concordance with FFR in patients with multivessel disease. Multiparametric CMR integrating stress-rest perfusion CMR and flow measurement in the coronary sinus is useful for detecting reduced FFR in multivessel disease.

Attempt to Harvest a Sufficient Number of Mononuclear Cells in an Appropriate Blood Product Volume By Modification of the Default Apheresis Setting.

To harvest for T cell therapy, a 1.6-fold higher number of CD3+ T cells was collected with MNC mode (N = 10) compared with Auto PBSC mode (N = 5) in COBE Spectra cell separator, but the blood product volume was increased by 3.5-fold. For therapeutic angiogenesis therapy, apheresis was initially performed using Auto PBSC mode (N = 4) to fine tune the blood product volume to omit cell concentration, but the collected number of mononuclear cells was lower than expected. However, an increase of the harvest cycle number from 3.8 ± 0.5 to 7.4 ± 2.0 cycles (N = 19) resulted in a 2.1-fold higher number of collected mononuclear cells (8.7 ± 4.1 × 109 vs. 4.1 ± 1.0 × 109 cells, P < 0.05). The increase in blood product volume by this modification appeared to be lower than that expected with MNC mode. These data show that optimal harvesting can be achieved by modification of default collection settings.

Antialbuminuric effect of eplerenone in comparison to thiazide diuretics in patients with hypertension.

This study investigated the effects and safety of eplerenone or thiazide diuretics in patients with hypertension and albuminuria (pretreatment urinary albumin/creatinine ratio ≥10 mg/gCr) treated with an angiotensin II receptor blocker. The primary end point was the mean percent change in the urinary albumin/creatinine ratio from baseline to 48 weeks. An efficacy analysis was performed in 195 patients (98 in the eplerenone group and 97 in the thiazide group). Systolic and diastolic blood pressures at 48 weeks were similar in the two groups. The mean percent change in the urinary albumin/creatinine ratio from baseline to 48 weeks was similar in the two groups (P=.804). In the safety analysis, the withdrawal rates for adverse events were similar in both groups. The antialbuminuric effects and safety of eplerenone therapy were similar to those of thiazide diuretics when combined with an angiotensin II receptor blocker in patients with hypertension and albuminuria.

Differential inhibitory effects of mu-opioids on substance P- and capsaicin-induced nociceptive behavior in mice.

The antinociceptive mechanisms of the selective mu-opioid receptor agonists [D-Ala2,NMePhe4,Gly(ol)5]enkephalin (DAMGO), H-Tyr-D-Arg-Phe-beta-Ala-OH (TAPA) or H-Tyr-D-Arg-Phe-beta-Ala-NH2 (TAPA-NH2) against substance P (SP)- or capsaicin-elicited nociceptive behaviors was investigated in mice. DAMGO, TAPA or TAPA-NH2 given intrathecally inhibited the nociceptive behaviors elicited by intrathecally administered SP or capsaicin, and these antinociceptive effects were completely eliminated by intrathecal co-administration with D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), a selective mu-opioid receptor antagonist. Pretreatment subcutaneously with naloxonazine, a selective mu1-opioid receptor antagonist, partially attenuated the antinociceptive effect of TAPA-NH2, but not DAMGO and TAPA, against SP. However, the antinociception induced by TAPA, but not DAMGO and TAPA-NH2, against capsaicin was significantly inhibited by naloxonazine. On the other hand, co-administration intrathecally with Tyr-D-Pro-Trp-Gly-NH2 (D-Pro2-Tyr-W-MIF-1), a selective mu2-opioid receptor antagonist, significantly attenuated the antinociceptive effects of DAMGO, but not TAPA and TAPA-NH2, against capsaicin, while the antinociceptions induced by three opioid peptides against SP were significantly inhibited by D-Pro2-Tyr-W-MIF-1. These results suggest that differential inhibitory mechanisms on pre- and postsynaptic sites in the spinal cord contribute to the antinociceptive effects of the three mu-opioid peptides.

Involvement of spinal mu1-opioid receptors on the Tyr-d-Arg-Phe-sarcosine-induced antinociception.

The involvement of spinal mu-opioid receptor subtypes on the antinociception induced by i.t.-administered Tyr-D-Arg-Phe-sarcosine (TAPS), a N-terminal tetrapeptide analog of dermorphin, was determined in mice tail-flick test. Intrathecal administration of TAPS produced the marked inhibition of the tail-flick response in a dose-dependent manner. The antinociception induced by TAPS was completely eliminated by i.t.-co-administration of Tyr-D-Pro-Phe-Phe-NH2 (D-Pro2-endomorphin-2), the mu1-opioid receptor antagonist, whereas i.t. co-treatment with Tyr-D-Pro-Trp-Phe-NH2 (D-Pro2-endomorphin-1) or Tyr-D-Pro-Trp-Gly-NH2 (D-Pro2-Tyr-W-MIF-1), the mu2-opioid receptor antagonists, did not affect the TAPS-induced antinociception. In contrast, the antinociception induced by i.t.-administered [D-Ala2,N-MePhe4,Gly-ol5]enkephalin was significantly attenuated by i.t.-co-administration of D-Pro2-endomorphin-1 or D-Pro2-Tyr-W-MIF-1, but not D-Pro2-endomorphin-2. These results suggest that TAPS may stimulate spinal mu1-opioid receptors to produce the antinociception.

New coronary aneurysm formation and malapposition after zotarolimus-eluting stent implantation in Kawasaki disease.

Coronary artery involvement is the most important complication of Kawasaki disease. Coronary artery bypass surgery has been performed for ischemic heart disease caused by Kawasaki disease, however, long-term coronary graft patency is not satisfactory. Therefore, percutaneous coronary intervention (PCI) has its role in Kawasaki disease-related coronary artery disease. The incidence of new aneurysm is lower following stent implantation than balloon dilatation alone, even if a higher balloon pressure is applied. However, there are few reports about the efficacy of drug-eluting stent implantation for Kawasaki disease with coronary artery disease. Here, we describe a case of new coronary aneurysm formation and malapposition after zotarolimus-eluting stent implantation in Kawasaki disease. .

Use of corticosteroids in the treatment of cholesterol crystal embolism after cardiac catheterization: a report of four Japanese cases.

Cholesterol crystal embolism (CCE) is a serious complication associated with invasive vascular procedures. The prognosis of the renal involvement type of CCE is very poor, and there is currently no established treatment, other than supportive therapy. We herein report four cases of CCE with severe atherosclerosis wherein the renal function progressively deteriorated after cardiac catheterization. In three of the four patients, low-dose corticosteroids (0.3 mg/kg/day) improved the renal function, whereas the fourth patient died from CCE of the digestive system. This report reviews the literature on CCE and discusses possible therapeutic options.

Marked improvement of renal failure and severe hypertension after renal artery stenting in the solitary functioning kidney.

Atherosclerotic renal artery stenosis (ARAS) can cause resistant hypertension, progressive renal failure and/or cardiorenal syndrome. Although no randomized study to demonstrate the superiority of renal stenting over medical treatment is available, a case-sensitive approach is required for the treatment of ARAS. Here, we describe a case report of a symptomatic ARAS patient with a solitary functioning kidney in which successful detection of ARAS by ultrasonography examination with the Doppler method and timely renal artery stenting were performed. .

A case of aortic thrombosis and embolism preceding the progression of early esophageal cancer.

Aortic thrombosis is rare, especially in non-atherosclerotic aortae. A 51-year-old woman presented with intermittent claudication in the right lower extremity. She was diagnosed as having peripheral artery disease on ultrasound. A computed tomography scan showed a large, sessile, aortic mural thrombus from the infrarenal abdominal aorta to the right common iliac artery. An arteriogram showed an abrupt occlusion of the right superficial femoral artery with collateral arteries. She had no risk factors for atherosclerosis. Interestingly, this occurred before early esophageal cancer progressed. Heparin was administered intravenously and later changed to warfarin. In the follow-up period, the thrombus disappeared, and her symptoms improved. A careful investigation for malignant disease is needed when aortic thrombus occurs in patients with no atherosclerosis risk factors. .