Very Late Stent Thrombosis after Discontinuation of Antiplatelet Agents during Anticoagulation Therapy in a Patient with Peri-stent Contrast Staining after Implantation of a Second-generation Drug-eluting Stent.

A 54-year-old man was admitted to our hospital due to intermittent chest pain. He had a history of acute myocardial infarction, and peri-stent contrast staining had been observed at the stent implantation site. The patient previously underwent anticoagulation therapy for left ventricular thrombus and antiplatelet therapy to prevent stent thrombosis. More than one year after implantation of a drug-eluting stent, antiplatelet drugs were discontinued, and anticoagulant alone was prescribed according to the guidelines, which resulted in very late stent thrombosis. The risks of both bleeding and thrombosis must be fully considered when deciding whether or not to discontinue antiplatelet therapy during anticoagulation therapy.

Clinical effectiveness and adverse events associated with tolvaptan in patients above 90 years of age with acute decompensated heart failure.

With the aging society, the number of very-elderly (VE) patients with acute decompensated heart failure (ADHF) is increasing. Although tolvaptan is recommended for patients with ADHF in whom conventional diuretic therapy is ineffective, few reports exist on VE patients over 90 years of age. Therefore, we aimed to evaluate the clinical effectiveness and adverse events associated with tolvaptan in VE patients with ADHF. From January 2011 to December 2018, we retrospectively studied 180 patients with ADHF who were first administered tolvaptan during hospitalization. Patients were divided into two groups, namely, VE patients who were ≥ 90 years of age (n = 32) and not-VE patients (NVE) who were < 90 years of age (n = 148). The primary effective endpoints were the total urine volume and change in body weight. The safety endpoints evaluated were the incidence of hypernatremia (≥ 150 mEq/L) and worsening renal function (WRF) at any time during hospitalization. The median [interquartile range] patient age was 93 [91-94] years in the VE group and 80 [69-85] years in the NVE group. The mean dose of tolvaptan for the first week of administration was similar between groups (7.9 ± 5.0 mg, VE group; 7.3 ± 3.7 mg, NVE group; p = 0.52). There were no significant differences between the two groups in the total urine volume at 24 h (1901 ± 666 mL, VE group; 2101 ± 1167 mL, NVE group; p = 0.33) and that at 48 h (3707 ± 1274 mL, VE group; 4195 ± 1990 mL, NVE group; p = 0.19) and in the mean change in body weight (- 2.5 ± 2.0 kg, VE group; -2.7 ± 2.4 kg, NVE group; p = 0.70). The median duration of hospitalization was 24 [20-9] and 31 [20-42] days in the VE and NVE groups, respectively (p = 0.67). The incidence of hypernatremia (6.3% (2/32), VE group; 3.4% (5/148), NVE group; p = 0.61) and WRF (25.0% (8/32) VE group; 19.6% (29/148), NVE group; p = 0.31) was similar between the groups. In conclusion, tolvaptan has similar clinical effectiveness in increasing urine volume and decreasing body weight, without increased adverse events, in VE patients with ADHF who were ≥ 90 years of age compared to NVE patients with ADHF.

Development of Alveolar Hemorrhage in a Patient with Acute Myocardial Infarction Complicated with Essential Thrombocythemia.

BACKGROUND Essential thrombocythemia (ET) is a risk factor both for bleeding caused by abnormal platelet function and for thrombus formation caused by excessive platelet proliferation. We present a rare case of alveolar hemorrhage after dual antiplatelet therapy (DAPT), a serious bleeding complication of antithrombotic therapy, in a patient with an acute myocardial infarction complicated by ET. CASE REPORT A 75-year-old man was treated for ET. He experienced an acute myocardial infarction, and an emergent percutaneous coronary intervention was subsequently performed. DAPT was started just before stent implantation. Because a left ventricular thrombus was suspected in spite of DAPT, anticoagulant therapy with heparin was added. On day 7, a large amount of hemoptysis was observed, and alveolar hemorrhage was diagnosed. Although the antithrombotic treatment was de-escalated from DAPT to single antiplatelet therapy, no stent thrombosis or recurrence of alveolar hemorrhage was observed. CONCLUSIONS In ET patients, reduced platelet function due to thrombocytosis and strong antithrombotic therapy may cause an excessive bleeding risk. Switching from DAPT to antiplatelet monotherapy at the early stage of stent implantation is a treatment option in situations in which excessive bleeding risk is a concern.

The Effectiveness of Target Low-Density Lipoprotein Cholesterol Achieved with Strict Management in Secondary Prevention of Long-Term Coronary Events in Japanese Patients.

BACKGROUND: In the secondary prevention of long-term coronary events, a target value of low-density lipoprotein cholesterol (LDL-C) < 100 mg/dL is recommended as standard management in Japanese guidelines. However, the effectiveness of strict management on lowering LDL-C remains unclear. OBJECTIVES: To clarify whether strict management of LDL-C < 70 mg/dL is more effective in preventing long-term coronary event recurrence than standard management. METHODS: We retrospectively investigated 344 patients with previous percutaneous coronary interventions who underwent late coronary angiography to examine recurrence of cardiac ischemia beyond the early restenosis period from January 2007 to August 2019. Patients were stratified into three groups according to achieved LDL-C value; LDL-C < 70 mg/dL (n = 53), 70 to < 100 mg/dL (n = 130), and ≥ 100 mg/dL (n = 161). Endpoints were acute coronary syndrome (recurrent-ACS) and late coronary revascularization. RESULTS: After follow-up (median 6.0 years), 200 patients (58%) underwent late coronary revascularization, including 94 recurrent-ACS. The incidence of recurrent-ACS was significantly lower in the patients who achieved LDL-C < 70 mg/dL than in those with LDL-C 70 to < 100 mg/dL and LDL-C ≥ 100 mg/dL (p = 0.009 and p = 0.001, respectively). There was no significant difference between the patients with LDL-C 70 to < 100 mg/dL and LDL-C ≥ 100 mg/dL (p = 0.140). There was also no significant difference in late revascularization between the patients with LDL-C < 70 mg/dL and LDL-C 70 to < 100 mg/dL. In patients with LDL-C < 100 mg/dL (n = 183), LDL-C [hazard ratio (HR) 1.035, p = 0.007] and HbA1c (HR 1.338, p = 0.001) were independently associated with recurrent-ACS. CONCLUSIONS: In Japanese patients, LDL-C was a residual risk for recurrent-ACS even after recommended standard LDL-C lowering management target values had been achieved.

Comparison of the low-density lipoprotein cholesterol target value and the preventive effect of statins in elderly patients and younger patients.

OBJECTIVE: To assess whether the low-density lipoprotein cholesterol (LDL-C) target value and preventive effect of statins are different between elderly and younger patients. METHODS: We investigated 304 patients with previous percutaneous coronary intervention who underwent coronary angiography from January 2007 to December 2016 for examination of recurrent ischemia beyond the early restenosis. Patients were classified into two groups: age ≥ 75 years (elderly group: n = 140) and < 75 years (younger group: n = 164). Relationships between the achieved LDL-C level, incidence of late coronary events, and the effectiveness of statins were evaluated. RESULTS: During follow-up, 179 patients underwent late coronary revascularization. Recurrent ischemia presenting as acute coronary syndrome (ACS) occurred in 83 cases. Kaplan-Meier curve analysis revealed that in the younger group, recurrent ACS was significantly lower in patients with LDL-C < 70 mg/dL than in those with LDL-C ranging from 70 to < 100 mg/dL (P = 0.035); however, there was no difference between these in the elderly group (P = 0.863). Instead, recurrent ACS was less frequent in patients with LDL-C ranging from 70 mg/dL to < 100 mg/dL than in those with LDL-C ≥ 100 mg/dL in the elderly group (P = 0.033). Statin use was associated with decreased recurrent ACS (P = 0.005); moreover, only using statins was an independent predictor in the elderly group (HR: 0.375; P = 0.007). CONCLUSIONS: Strict control of LDL-C to < 70 mg/dL was effective for reducing the incidence of recurrent ACS in younger patients. However, LDL-C < 100 mg/dL might be sufficient as the target value of LDL-C-lowering therapy for secondary prevention of ischemic events in Japanese elderly patients.

A Comparison between the Instantaneous Wave-free Ratio and Resting Distal Coronary Artery Pressure/Aortic Pressure and the Fractional Flow Reserve: The Diagnostic Accuracy Can Be Improved by the Use of both Indices.

Objectives The fractional flow reserve (FFR) is an index of the severity of coronary stenosis that has been clinically validated in several studies. The instantaneous wave-free ratio (iFR) and the resting distal coronary artery pressure/aortic pressure (Pd/Pa) are nonhyperemic pressure-derived indices of the severity of stenosis. This study sought to examine the diagnostic accuracy of the iFR and resting Pd/Pa with respect to hyperemic FFR. Methods Following an intracoronary injection of papaverine, the iFR, resting Pd/Pa, and FFR were continuously measured in 123 lesions in 103 patients with stable coronary disease. Results The iFR and resting Pd/Pa values were strongly correlated with the FFR (R=0.794, p<0.001, R=0.832, p<0.0001, respectively). A receiver operator curve (ROC) analysis revealed that the optimal iFR cut-off value for predicting an FFR of <0.80 was 0.89 (AUC 0.901, sensitivity 84.1%, specificity 80.0%, positive predictive value 69.8%, negative predictive value 90.0%, diagnostic accuracy 81.3%), while the optimal resting Pd/Pa cut-off value was 0.92 (AUC 0.925, sensitivity 90.9%, specificity 78.5%, positive predictive value 70.2%, negative predictive value 93.9%, diagnostic accuracy 82.9%). The lesions with an iFR value of ≤0.89 and a Pd/Pa value of ≤0.92 were defined as double-positive lesions, while the lesions with an iFR value of >0.89 and a Pd/Pa value of >0.92 were defined as double-negative lesions. In these 109 lesions, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 92.3%, 82.9%, 75.0%, 95.1%, and 86.2%, respectively. Conclusion This analysis demonstrated that the iFR and resting Pd/Pa were strongly correlated with the FFR and that the diagnostic accuracy of the iFR was similar to that of the resting Pd/Pa. The diagnostic accuracy can be improved with the use of both the iFR and the resting Pd/Pa.

Contrast-induced Hyperemia as an Alternative to Drug-induced Hyperemia in the Evaluation of the Fractional Flow Reserve in Coronary Lesions.

Objective Measuring the fractional flow reserve (FFR) requires the induction of coronary hyperemia, usually with adenosine, adenosine triphosphate (ATP), or papaverine. However, adenosine can induce rhythmic complications, and intracoronary boluses of papaverine that prolong the QT interval can cause ventricular tachycardia. Injection of contrast media, which is routinely performed to validate the FFR guidewire placement, also induces hyperemia and may be an alternative method of measuring the FFR. We evaluated the diagnostic accuracy of the FFR after contrast hyperemia (FFRcont) compared to FFR evaluated after intracoronary papaverine (FFRpp). Methods This study included 109 lesions in 93 patients (mean age 70.4±8.7 years) with stable coronary disease. The FFR was measured as follows: 1) baseline pressure value; 2) FFRcont after intracoronary contrast injection (iopamidol, 8 mL for left coronary artery [LCA] or 6 mL for right coronary artery [RCA]); 3) FFRpp after intracoronary injection of papaverine (12 mg for LCA or 8 mg for RCA). Results FFRcont values were strongly correlated with FFRpp (R=0.940, p<0.0001; FFRpp = FFRcont ×1.007-0.032). The best cut-off point in the receiver operator curve analysis for predicting a FFRpp <0.80 was 0.82 (area under the curve =0.980; sensitivity 95.1%, specificity 91.2%, positive predictive value 86.7%, negative predictive value 96.9%). Conclusion FFRcont is highly accurate for predicting FFRpp. An FFRcont threshold value of 0.82 provides excellent sensitivity and a negative predictive value. FFRcont is an alternative method of inducing hyperemia.

Development of an iatrogenic aneurysm nine months after pacemaker implantation: Consideration of causes and treatment.

Careful technique is required in pacemaker implantation to avoid serious iatrogenic complications. A 70-year-old woman on an anticoagulant agent underwent pacemaker implantation. Nine months after implantation, a 35-mm pulsatile mass appeared just near the cranial edge of the generator. An iatrogenic pseudoaneurysm was suspected because ultrasonography showed communication with the blood stream through tiny artery. The resected mass proved to be a pseudoaneurysm. This was a rare case of iatrogenic delayed pseudoaneurysm appearing nine months later. It is essential to keep in mind the risk of pseudoaneurysm after pacemaker implantation, especially when the patient takes anticoagulant agents. .

A case of subacute stent thrombosis after drug-coated balloon coronary angioplasty for in-stent restenosis under single anti-platelet therapy.

This report describes a case of subacute stent thrombosis (SAT) after drug-coated balloon (DCB). A 79-year-old male was investigated for stable angina. An in-stent restenosis (ISR) lesion was detected by coronary angiography. A skin reaction related to the anti-platelet agent thienopyridine was also observed at this time. Therefore, DCB was used to treat the ISR lesion under single anti-platelet therapy (aspirin). However, 3 days after percutaneous coronary intervention, SAT occurred. OCT did not reveal the underlying cause of SAT. Further data are needed to clarify the optimal duration of dual anti-platelet therapy after DCB.

The Difference between the optical coherence tomography (OCT) findings of newly progressed coronary lesions in symptomatic and asymptomatic patients.

BACKGROUND: Generally, newly progressed coronary lesions (NPCLs) are considered to be composed of lipid-rich plaques. In case of vulnerable plaque rupture, they may quickly become culprit lesions responsible for acute coronary syndromes. METHODS: Between September 2011 and September 2015, 2034 patients underwent scheduled follow-up coronary angiography (CAG) after percutaneous coronary intervention (PCI) in Tsuchiya General Hospital. Patients with NPCLs found by CAG during the follow-up period were evaluated by optical coherence tomography (OCT). NPCLs were defined as the lesions with less than 50% diameter stenosis, which progressed to more than 75% diameter stenosis within 3years after the previous CAG. Patients with restenosis after PCI were excluded. We compared OCT findings of NPCLs between symptomatic and asymptomatic patients. RESULTS: The follow-up CAG showed NPCLs in 64 patients (3.2%). OCT revealed fibrous plaque in 42 patients (65.6%) and thin-cap fibroatheroma in one patient. Thirteen patients had chest symptoms for one month before CAG and the remaining 51 patients were asymptomatic. The prevalence of fibrous plaque and intimal disruption or plaque rupture were not significantly different between symptomatic and asymptomatic patients (61.5% vs. 66.7%, p=0.752 and 30.8% vs. 11.8%, p=0.213, respectively). However, thrombi were more frequently observed in symptomatic patients (61.5% vs. 13.7%, p<0.001). CONCLUSIONS: The majority of NPCLs found in asymptomatic patients at follow-up CAG were not vulnerable; however, those found in symptomatic patients might be vulnerable. In clinical practice, NPCLs found in asymptomatic patients should be evaluated for functional severity of stenosis in order to determine the need for coronary revascularization.

Comparison of everolimus- and paclitaxel-eluting stents in dialysis patients.

BACKGROUND: We previously reported that the incidence of 1-year major adverse cardiac events (MACE) in patients treated with paclitaxel-eluting stents (PES) was lower than that in the sirolimus-eluting stents in dialysis patients. However, it remains unclear whether there are differences in clinical outcomes between everolimus-eluting stents (EES) and PES. METHODS: Between February 2010 and September 2013, 102 maintenance dialysis patients with 135 lesions treated with EES were compared to 107 maintenance dialysis patients with 147 lesions treated with PES. One-year clinical outcomes were investigated. RESULTS: Diabetes mellitus was present in 64.7% in the EES group and 71.0% in the PES group (p = 0.33). Heavy calcification was in 27.4% vs. 34.0% (p = 0.23). Rotational atherectomy was undergone in 11.1% vs. 23.1% (p < 0.01). Total stented length was not significantly different (23.5 ± 14.6 mm vs. 24.4 ± 13.2 mm, p = 0.60). One patient in the EES group was lost to follow up. At 12 months, MACE occurred in 13.2% in the EES group and 17.4% in the PES group (p = 0.25). Target lesion revascularization (TLR) was observed in 9.5% vs. 10.4% respectively (p = 0.77). Mortality was 11.8% vs. 13.1% (p = 0.35). Cardiac death was 5.0% vs. 7.7% (p = 0.09). Definite stent thrombosis was observed in 2.0% vs. 0% (p = 0.14). Subgroup analysis in patients with diabetes mellitus revealed no significant differences in MACE (12.7% vs. 14.9%, p = 0.36), TLR (8.3% vs. 7.4%, p = 0.42), mortality (13.7% vs. 13.2%, p = 0.28), and cardiac death (6.3% vs. 8.0%, p = 0.15) between the two groups. CONCLUSIONS: One-year clinical outcomes following EES and PES implantations are similar in dialysis patients.

Validation of lactate level as a predictor of early mortality in acute decompensated heart failure patients who entered intensive care unit.

BACKGROUND: The significance of routine measurement of lactate level is unclear in patients with critical acute decompensated heart failure (ADHF). METHODS AND RESULTS: Consecutive 754 patients who were admitted to the intensive care unit (ICU) in our hospital from January 2007 to March 2012 and given a diagnosis of ADHF were eligible for retrospective entry into the registry. Lactate level was measured on admission from routine arterial blood sample and we investigated by comparing the lactate level and parameters of conventional in-hospital mortality predictors. Among the patients, 88 (12%) died during hospitalization. The lactate level had great power to predict in-hospital mortality, as suggested by the c-statistics of 0.71. The occurrence of in-hospital death was more pronounced in patients with high levels of lactate (>3.2mmol/l) and the tendency was observed in patients in both the acute coronary syndrome (ACS) group and non-ACS group. In multivariate analysis, elevated lactate levels remained an independent predictor of in-hospital death (odds ratio, 2.14; 95% confidence interval, 1.10-4.21; p=0.03). CONCLUSIONS: Elevated levels of arterial lactate on admission were related to worse in-hospital mortality in patients with ADHF either with or without ACS, suggesting that the presence of high lactate in patients who enter the ICU with ADHF could help stratify the initial risk of early mortality.

Comparison of sirolimus- and paclitaxel-eluting stents in patients with moderate renal insufficiency: results from the J-DESsERT trial.

BACKGROUND: It is unclear whether there are differences in clinical outcomes between sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) in patients with moderate renal insufficiency (RI). METHODS: The Japan-Drug Eluting Stents Evaluation; a Randomized Trial (J-DESsERT) was a prospective, randomized multicenter trial which compared 1:1 coronary stenting between SES and PES patients. Patient with serious RI (serum creatinine value 2mg/dL or higher) were excluded. Patients were classified into 2 arms according to renal function: a non-RI arm of 2220 patients (SES 1094 and PES 1126 patients with estimated glomerular filtration rate (eGFR) ≥60 mL min(-1) 1.73 m(-2)) and an RI arm of 1206 patients (SES 613, PES 593 with 30≤eGFR <60 mL min(-1) 1.73 m(-2)). RESULTS: At 12 months, the primary endpoint of target vessel failure in the non-RI arm occurred in 6.0% in the SES group and 8.7% in the PES group (p=0.02). In the RI arm, this occurred in 5.7% and 8.1% (p=0.10). Mortality rates were 0.8% vs 0.7% (p=0.78) in the non-RI arm, and 2.2% vs 2.1% (p=0.90) in the RI arm. Cardiac death was 0.4% vs 0.1% (p=0.17) in the non-RI arm, and 1.0% vs 1.0% (p=0.96) in the RI arm. Mortality was higher in patients with RI than those without RI (2.1% vs 0.8%; p<0.01). Cardiac death rates increased in the RI arm compared with those in the non-RI arm (1.0% vs 0.2%; p<0.01). CONCLUSIONS: Regardless of the presence or absence of moderate RI, differences in outcomes between SES and PES change little except mortality and cardiac death.

Causes of very late stent thrombosis investigated using optical coherence tomography.

OBJECTIVE: Very late stent thrombosis (VLST) remains an unresolved problem, and recent reports have indicated that VLST onset can occur in patients treated with both drug-eluting stents (DES) and bare metal stents (BMS). We evaluated the causes of VLST using optical coherence tomography (OCT). METHODS: OCT was performed in 22 patients (12 DES-treated patients, 10 BMS-treated patients). Because two instances of VLST occurred simultaneously in one case in the DES group, the DES group comprised 13 lesions, while the BMS group comprised 10 lesions. All struts were counted in each frame, and the proportion of uncovered or malapposed struts was calculated based on the overall number of struts in the stent. RESULTS: The interval from stent implantation to VLST onset was significantly longer in the BMS group. The proportion of uncovered struts and the ratio of malapposed struts were significantly higher in the DES group than in the BMS group. The OCT analysis demonstrated intimal hyperplasia or intimal disruption in all patients in the BMS group. However, in the DES group, severe hyperplasia and/or neoatherosclerosis was observed in only eight lesions (61.5%), while uncovered and malapposed struts were involved in the other lesions. CONCLUSION: In most BMS-treated lesions, it appeared that VLST was caused by the occurrence of neoatherosclerosis after stent implantation. The causes of VLST in DES-treated lesions are more various and complicated than those observed for BMS-treated lesions.

Effect of statin on the 5 years clinical outcomes in dialysis patients treated with sirolimus-eluting stent.

OBJECTIVE: The optimal medication therapies are recommended in patients with coronary artery disease even after the coronary revascularization. However, the information of optimal medical therapy in dialysis population is scant. We assessed the efficacy of statin on the clinical outcomes after Sirolimus-eluting stent (SES) implantation in patients with and without dialysis. METHODS AND RESULTS: We analyzed date from 843 consecutive patients who successfully treated with SES in our institution between August 2004 and November 2006. Among patients, 96 patients (11.4%) were undergoing dialysis. In non-dialysis patients, 405 patients (54%) were treated with statin at hospital discharge. In dialysis patients, only 16 patients (17%) were treated with statin. In non-dialysis patients, mortality rate was significantly lower in patients treated with statin than those without statin (4.4% vs. 13.9%, p<0.0001). While in dialysis patients, mortality rate was similar between patients treated with and without statin (56.3% vs. 57.6%, p=0.86). After adjusting for confounders, the hazard ratios for mortality were 0.39 (95% confidence interval (CI), 0.14-0.99; p=0.047) in non-dialysis patients and 1.79 (95% CI, 0.39-7.86; 0.45) for dialysis patients. The interaction probability between statin use and dialysis for mortality was 0.016. CONCLUSION: The use of statin may have beneficial effect on reducing mortality rate in patients after SES implantation in non-dialysis patients. However, such favorable effect was not observed in dialysis population.

Comparison of heart-type fatty acid binding protein and sensitive troponin for the diagnosis of early acute myocardial infarction.

BACKGROUND: The current development of serological biomarkers allows detection of smaller myocardial necrosis and early acute myocardial infarction (AMI). We evaluated the relevance of the heart-type fatty acid binding protein (H-FABP) assay, which has recently been approved in Japan, for early diagnosis of AMI as compared with the sensitive troponin assay. METHODS: This is an observational study in a single center. From 2010 July to 2011 January, 114 patients who presented with symptoms suggestive of AMI were enrolled. RESULTS: AMI was adjudicated in 45 patients (40%). The diagnostic accuracy of measurements obtained at presentation for AMI, as quantified by the area under the receiver-operating-characteristic curve (AUC), was significantly lower with H-FABP assay than the sensitive troponin assay [AUC for H-FABP, 0.59; 95% confidence interval (CI) 0.48-0.70; and for troponin I, 0.89; 95% CI, 0.83-0.94; P<.0001]. Among patients who presented within 2h after the onset of chest pain, the AUC for H-FABP was even low as compared with sensitive troponin (0.55; 0.39-0.72 vs. 0.89; 0.80-0.98, p<0.001). The clinical sensitivity for the diagnosis of AMI with the cutoff point of 99 th percentile was similar in both assays (81% and 81%, respectively), however, the specificity was extremely low in the H-FABP assay as compared with sensitive troponin assay (19% and 79%, respectively). CONCLUSION: The measurement of H-FABP in 114 consecutive patients with chest pain suggestive of AMI showed no improvement of diagnosis for early AMI as compared with the current sensitive troponin assay because of its extremely low specificity.