Biomarkers for Risk Stratification in Patients With Type A Acute Aortic Dissection.

Type A acute aortic dissection (AAD) is a fatal disease and thus, accurate and objective risk stratification is essential. In this study, we evaluated the prognostic value of readily available and assessable biomarkers in patients with type A AAD. This was a retrospective, multicenter, observational study. A total of 703 patients with type A AAD diagnosed using contrast-enhanced computed tomography were included. Therapeutic strategies were left to the physician's discretion in a real-world clinical setting. The prognostic value for in-hospital mortality was examined in 15 circulating biomarkers on admission, which are routinely available in clinical practice. Of the 703 patients, 126 (17.9%) died during the hospitalization. Of the 15 biomarkers, the multivariable analysis identified positive cardiac troponin, a low total bilirubin (T-Bil) level, and increased levels of brain natriuretic peptide (BNP) and lactate dehydrogenase (LDH) as significant predictors of in-hospital death. The receiver operating characteristics curve analysis showed that these 4 biomarkers had an independent additive prognostic value. With the cut-off values of T-Bil, BNP, and LDH, in combination with positive troponin, the increase in the number of positive biomarkers was progressively associated with higher in-hospital mortality from 1.3% to 9.8%, 20.5%, 36.4%, and 75.0% (p <0.001). In conclusion, in patients with type A AAD, positive cardiac troponin, a low T-Bil level, and increased levels of BNP and LDH on admission were related to higher in-hospital mortality, with an incremental prognostic value, suggesting that the readily available and assessable biomarkers can aid in decision-making in therapeutic strategies.

Clinical characteristics and outcomes in patients with acute type A aortic intramural hematoma.

BACKGROUND: Although type A acute aortic dissection (AAD) including classic double-channel aorta and intramural hematoma (IMH) is a life-threatening condition, the prognostic impact and predictors of IMH remain to be established. The present study evaluated the prevalence, baseline characteristics, and outcomes of IMH as compared with classic non-thrombosed type A AAD. METHODS: This multicenter registry in Japan retrospectively included 703 patients with type A AAD. IMH was defined as a crescentic or circular area along the ascending aortic wall without contrast enhancement on computed tomography (CT). Non-thrombosed type A AAD was defined as the classic double-channel ascending aorta on contrast-enhanced CT. The primary endpoint was in-hospital mortality. RESULTS: Of the 703 patients with type A AAD, 312 (44.3%) had IMH. Older age was an only baseline patient factor significantly associated with the presence of IMH in the multivariable analysis. The longitudinal extent of dissection was greater in patients with classic non-thrombosed AAD than those with IMH, resulting in an increased risk of end-organ malperfusion in the classic AAD group. During the hospitalization, 41 (13.1%) and 85 (21.7%) patients with and without IMH died (p < 0.001). IMH was associated with lower in-hospital mortality in a multivariable model, irrespective of age and the implementation of surgery. CONCLUSIONS: The present study showed that IMH on CT was frequent among patients with type A AAD. Although IMH was more likely to be present in the elderly, its effect on the better survival was independent of age and surgical treatment.

Right versus left coronary artery involvement in patients with type A acute aortic dissection.

BACKGROUND: Type A acute aortic dissection (AAD) complicated by coronary malperfusion is a life-threatening disease. In the present study, we compared the clinical characteristics and prognostic impact of treatment strategies including surgical treatment and percutaneous coronary intervention (PCI) in type A AAD patients with RCA and LCA involvement. METHODS: This multicenter registry included 220 patients with type A AAD and either RCA or LCA involvement. Treatment strategies were left to treating physicians. The primary endpoint was in-hospital death. RESULTS: Of 220 patients, 115 (52.3%) and 105 (47.7%) had RCA and LCA involvement. Patients with LCA involvement were more1 likely to present with Killip class IV on admission than those with RCA involvement. Coronary angiography was performed in 52 of 220 (23.6%) patients, among whom 39 (75.0%) underwent subsequent PCI. During the hospitalization, 93 (42.3%) patients died. Patients with LCA involvement had an increased risk of in-hospital mortality compared to those with RCA involvement (54.3% vs. 31.3%, p < 0.001). In patients with RCA involvement, multivariable analysis identified Killip class IV and no surgical treatment as predictors of in-hospital death, while PCI and surgical treatment were indicated as factors associated with lower in-hospital mortality in patients with LCA involvement. CONCLUSIONS: The rates of RCA and LCA involvement were similar in type A AAD. Immediate PCI as a bridge to subsequent surgical treatment might improve survival in patients with type A AAD complicated by coronary malperfusion, especially in those with LCA involvement.

Prognostic Impact of Branch Vessel Involvement on Computed Tomography versus Clinical Presentation of Malperfusion in Patients With Type a Acute Aortic Dissection.

Type A acute aortic dissection (AAD) is a life-threatening disease. The use of contrast-enhanced computed tomography (CT) for diagnosing AAD has increased, and CT can provide pathophysiologic information on dissection such as intramural hematoma (IMH), longitudinal extent of dissection, and branch vessel involvement. However, the prognostic impact of these CT findings is poorly investigated. This multicenter registry included 703 patients with type A AAD. The longitudinal extent of dissection and IMH was determined on CT. Branch vessel involvement was defined as dissection extended into coronary, cerebral, and visceral arteries on CT. The evidence of malperfusion was defined based on clinical presentations. The primary endpoint was in-hospital death. Of 703 patients, 126 (18%) died during hospitalization. Based on contrast-enhanced CT findings, longitudinal extent of dissection was not associated with in-hospital death, while patients with IMH had lower in-hospital mortality than those without (13% vs 22%, p = 0.004). Coronary, cerebral, and visceral artery involvement on CT was found in 6%, 55%, and 32%. In patients with coronary artery involvement, 90% had clinical coronary malperfusion, while only 25% and 21% of patients with cerebral and visceral artery involvement had clinical evidence of corresponding organ malperfusion. Multivariable analysis showed evidence of malperfusion as a significant factor associated with in-hospital mortality. In conclusions, branch vessel involvement on CT was not always associated with end-organ malperfusion in patients with type A AAD, especially in cerebral and visceral arteries. Clinical evidence of malperfusion was significantly associated with in-hospital mortality beyond branch vessel involvement on CT.

Investigation of MDA-LDL (malondialdehyde-modified low-density lipoprotein) as a prognostic marker for coronary artery disease in patients with type 2 diabetes mellitus.

BACKGROUND: Although increased circulating levels of malondialdehyde-modified low-density lipoprotein (MDA-LDL) are associated with coronary artery disease (CAD), there is no direct evidence that increased MDA-LDL is a prognostic factor for CAD. METHODS: Forty-two patients (20 diabetic and 22 non-diabetic patients) who underwent percutaneous coronary intervention (PCI) were enrolled, and their baseline MDA-LDL levels were determined by immunoassay. Follow-up coronary angiography was performed at 2 to 7 months post-PCI. The patients were then divided into 2 groups, with in-stent restenosis (ISR) (n=13) and without ISR (n=29), and the baseline MDA-LDL levels were compared. We also studied 34 diabetics with CAD for up to 57 months until the onset of the next coronary event. RESULTS: In the diabetic patients, the mean MDA-LDL level was significantly higher in those with ISR than in those without ISR (151+/-61 vs. 90+/-26 U/l, p=0.010). A baseline MDA-LDL value of 110 U/l for differentiating between diabetics with and without ISR was defined as the cut-off value. Kaplan-Meier analysis demonstrated that a circulating MDA-LDL of ≥ 110 U/l correlated significantly with a higher prevalence of cardiac events than MDA-LDL <110 U/l (p=0.032). CONCLUSIONS: Circulating MDA-LDL is a useful prognostic marker for future cardiac event in diabetic patients with CAD.

Percutaneous coronary intervention causes increase of serum cystatin C concentration even in the patients with a low risk of contrast-induced nephropathy.

Contrast-induced nephropathy (CIN) is an important complication of coronary angiography (CAG) and percutaneous coronary intervention (PCI). The aim of this study was to examine the effect of CAG and PCI to renal function in patients with a low risk of CIN by measuring serum cystatin C concentration. The patients were classified into 3 groups; CAG group, elective PCI group, and emergency PCI group. Enrolment continued until 100 patients were included in each of the 3 groups. The exclusion criteria were as follows; (1) serum creatinine concentration >1.5 mg/dL, (2) age >80 years, (3) cardiogenic shock, (4) use of mechanical ventilation or intra-aortic balloon pump, (5) history of renal failure, and (6) quantity of contrast used > maximum radiographic contrast dose. Blood samples for serum cystatin C analysis were collected before and 3 months after the index procedure. Two patients in the CAG group, 4 patients in the elective PCI group, and 12 patients in the emergency PCI group developed CIN. Multivariate analysis identified the predictors of CIN: pre-procedural cystatin C concentration >1.04 mg/L, contrast volume >150 mL and emergency procedure. In the elective PCI group and emergency PCI group, serum cystatin C concentration was significantly increased 3 months after PCI procedure. Even patients with a low risk of CIN developed CIN after CAG and PCI, which caused increase of serum cystatin C concentration. We should become more aware of the possible development of CIN and avoid performing unnecessary CAG and PCI procedure as far as possible.

Restenosis after implantation of sirolimus-eluting stent begins suddenly, shows short term progression, and stops suddenly.

BACKGROUND AND PURPOSE: The peak of restenosis in patients implanted with bare metal stents (BMS) is thought to be 6 months after BMS implantation, but the development of restenosis with respect to time and the peak of restenosis in patients implanted with drug-eluting stents (DES) is not known. This study aims to reveal the rate of development of restenosis with respect to time in patients implanted with DES. METHODS: A total of 282 patients who underwent sirolimus-eluting stent (SES) implantation in native coronary arteries at our hospital were evaluated by serial quantitative angiography at 3 and 6 months, and based on the latter results, at 1 and 2 years after SES implantation. Clinical data were collected for up to 3 years. RESULTS: Three-year follow-up data were obtained for 261 patients. The 3-year incidence of clinically driven target-lesion revascularization (TLR) was 6.1% (16/261); of the 16 cases, 5 occurred at 3-month follow-up, 7 at 6-month angiographic follow-up, and 1 at 1-year follow up, respectively. While minimum lumen diameter (MLD) of these vessels that underwent TLR at 6 months decreased rapidly after the 3-month angiographic follow-up, MLD of the vessels with 50-70% stenosis at 6-month angiographic follow-up was almost unchanged at 1-year angiographic follow-up; however, 3 lesions required late (i.e. beyond 1 year) revascularization. CONCLUSIONS: It is difficult to predict SES restenosis by angiography. SES restenosis begins suddenly, shows short-term progression, and stops suddenly. However, treatment of de novo coronary stenosis with SES is associated with a sustained clinical benefit and a very low incidence of TLR.

Incidence of side-effects of dual antiplatelet therapy with clopidogrel and aspirin after coronary stent implantation.

There is little information about the incidence of the side-effects of clopidogrel in Japanese patients undergoing coronary stent implantation. The present study included 334 consecutive patients who were given clopidogrel (75 mg daily) after coronary stent implantation. Aspirin (100 mg daily) was used indefinitely. Clopidogrel was prescribed for at least 4 weeks in patients with bare metal stents and indefinitely in those with drug-eluting stents (DES). The duration of clinical follow-up was 164.7 ± 139.0 days. Half of the patients underwent stenting because of acute myocardial infarction. DES were used in 38% of the patients. Definite early stent thrombosis occurred in one patient (0.31%). There was one definite late stent thrombosis (0.31%). Side-effects of the clopidogrel were observed in 16 patients (4.9%). Liver dysfunction occurred in seven patients (2.1%), skin rash in six (1.8%), and bleeding in three (0.9%). There was no neutropenia or thrombocytopenia. The results of this study show that prescribing clopidogrel as well as aspirin is a safe treatment for Japanese patients undergoing coronary stenting.

Efficacy of thrombectomy for acute myocardial infarction-Special focus on its efficacy according to different infarct-related arteries.

BACKGROUND: The efficacy of thrombectomy during percutaneous coronary intervention (PCI) for ST-segment elevation acute myocardial infarction (STEMI) has not yet been fully evaluated. The aim of this retrospective study was to evaluate the usefulness of manual thrombectomy for STEMI and to clarify whether different infarct-related arteries (IRAs) influence the efficacy of thrombectomy. METHODS AND RESULTS: We enrolled 183 patients with STEMI who underwent PCI within 24h after onset between October 2001 and January 2004. We divided these patients into 2 groups, namely 88 patients who had undergone PCI after manual thrombectomy (Th+ group) and 95 patients who were treated with PCI alone (Th- group). The Th+ group had lower incidences of distal embolization and no-reflow phenomenon than the Th- group (6.8% vs. 27.4%, p=0.0003; and 5.7% vs. 23.2%, p=0.0009, respectively). The percentage of complete ST-segment resolution (STR) after PCI and left ventricular ejection fraction 6 months after the procedure were significantly higher in the Th+ group (43.2% vs. 20%, p=0.002; and 60.1% vs. 54.8%, p=0.004, respectively). Regarding different IRAs, the percentage of complete STR was significantly higher in patients with proximal left anterior descending coronary artery (LAD) and right coronary artery (RCA) lesions in the Th+ group (37.5% vs. 9.7%, p<0.05; and 59.5% vs. 30.3%, p<0.05, respectively). Incidences of adverse events were similar in both groups. CONCLUSIONS: Manual thrombectomy for STEMI can improve myocardial reperfusion after PCI and left ventricular function late after the procedure. With respect to different IRAs, manual thrombectomy for STEMI is more effective in proximal LAD and RCA lesions.

Prognostic significance of cystatin C in patients with ST-elevation myocardial infarction.

BACKGROUND: Cystatin C is reportedly a better endogenous marker of glomerular filtration rate than serum creatinine, so the prognostic value of cystatin C in patients with ST-elevation myocardial infarction (MI) was evaluated in the present study. METHODS AND RESULTS: A total of 71 patients who underwent percutaneous coronary intervention for ST-segment elevation MI <24 h from symptom onset were included. According to cystatin C level, patients were classified into 2 groups: (1) higher cystatin C group (n=33) and (2) lower cystatin C group (n=38). There was a trend toward more in-hospital deaths in patients with the higher cystatin C level compared with the lower cystatin C level group (15.2% vs 2.6%, P=0.06). Mean duration of clinical follow-up was 5.6 +/-2.8 months. There was no significant difference in death, reinfarction, disabling stroke or target lesion revascularization between the 2 groups. However, a higher incidence of rehospitalization for congestive heart failure was observed in patients with the higher cystatin C level than in those with the lower cystatin C level (15.2% vs 0%, P=0.01). CONCLUSIONS: Cystatin C may be associated with more cardiovascular events, mainly rehospitalization for congestive heart failure, after percutaneous coronary intervention in patients with ST-elevation MI.

Re-restenosis and target lesion revascularization after treatment of sirolimus-eluting stent restenosis: retrospective analysis of 4 Japanese hospitals.

BACKGROUND: There is limited information about optimal management of drug-eluting stent (DES) restenosis. This study evaluated the incidences of re-restenosis and re-target lesion revascularization (TLR) after the treatment of sirolimus-eluting stent (SES) restenosis. METHODS AND RESULTS: A total of 102 lesions in 101 patients who underwent TLR for SES restenosis were classified according to: (1) focal (lesion length < or = 10 mm) or non-focal restenosis (>10 mm); and (2) use of DES for TLR: (1) focal restenosis treated with DES (focal-DES, n=40); (2) focal restenosis treated by balloon angioplasty (focal-balloon, n=31); (3) non-focal restenosis with DES (non-focal-DES, n=17); and (4) non-focal restenosis by balloon angioplasty (non-focal-balloon, n=14). Re-restenosis and re-TLR were observed in 6 (19.4%) and 5 lesions (12.5%) of the focal-DES group, in 13 (65.0%) and 11 (35.5%) of the focal-balloon group, in 7 (50.0%) and 6 (35.3%) of the non-focal-DES group, and in 8 (61.5%) and 7 (50.0%) of the non-focal-balloon group, respectively (P<0.05 for restenosis and TLR between the focal-DES group and other groups). CONCLUSIONS: Re-DES implantation for focal DES restenosis results in lower re-restenosis and re-TLR rates compared to re-DES implantation for non-focal DES restenosis or conventional balloon angioplasty either for focal or non-focal DES restenosis.

Angiographic patterns of restenosis after sirolimus-eluting stent implantation.

BACKGROUND: Large-scale randomized trials demonstrate a high proportion of focal restenosis after drug-eluting stent (DES) implantation. On the other hand, recent reports have shown that in real-world practice a significant proportion of the restenosis is non-focal when DESs are used in unselected lesions. The present study evaluated angiographic patterns of restenosis after sirolimus-eluting stent (SES) implantation in Japan. METHODS AND RESULTS: Angiographic restenosis patterns of all consecutive restenotic lesions (n=124) after SES implantation were evaluated and classified according to the following scheme: focal (10 mm within the stent), proliferative (restenosis >10 mm in length extending outside the stent), and occlusive. There were 98 focal (79.0%), 15 diffuse (12.1%), and 5 proliferative restenoses (4.0%) and 6 total occlusions (4.8%). Focal intrastent restenosis was most dominant (42.7%). Proximal edge restenosis occurred in 22 lesions (17.7%). Multivariate analysis demonstrated diabetes mellitus (P<0.01) as an independent predictor of non-focal restenosis. CONCLUSIONS: Focal restenosis is predominant after SES implantation in real-world practice in Japan.

Plasma pre beta1-HDL level is elevated in unstable angina pectoris.

Pre beta1-HDL, a minor HDL subfraction consisting of apolipoprotein A-I (apoA-I), phospholipids and unesterified cholesterol, plays an important role in reverse cholesterol transport. Plasma pre beta1-HDL levels have been reported to be increased in patients with coronary artery disease (CAD) and dyslipidemia. To clarify the clinical significance of measuring plasma pre beta1-HDL levels, we examined those levels in 112 patients with CAD, consisting of 76 patients with stable CAD (sCAD) and 36 patients with unstable angina pectoris (uAP), and in 30 patients without CAD as controls. The pre beta1-HDL levels were determined by immunoassay using a specific monoclonal antibody (Mab55201) that we established earlier. The mean pre beta1-HDL level in the CAD patients was significantly higher than the level in the controls (34.8+/-12.9 mg/L vs. 26.6+/-6.9 mg/L, p<0.001). In addition, the mean pre beta1-HDL level was markedly higher in the uAP subgroup than in the sCAD subgroup (43.1+/-11.5mg/L vs. 30.9+/-11.7 mg/L, p<0.0001). These tendencies remained even after excluding dyslipidemic subjects. These results suggest that elevation of the plasma pre beta1-HDL level is associated with the atherosclerotic phase of CAD and may be useful for identifying patients with uAP.

Late stent thrombosis in patients receiving ticlopidine and aspirin after sirolimus-eluting stent implantation.

BACKGROUND: There is little information about the efficacy of ticlopidine plus aspirin after sirolimus-eluting stent (SES) implantation. METHODS AND RESULTS: The incidence of stent thrombosis was evaluated in 1,029 patients receiving ticlopidine and aspirin after SES deployment. Clinical follow-up was obtained in 98.9% (mean follow-up 17.0+/-7.9 months). Early stent thrombosis was observed in 5 patients (0.49%). There was 1 case each of late (0.1%) and very late stent thrombosis (0.1%). CONCLUSION: Late and very late stent thrombosis in Japanese patients receiving ticlopidine and aspirin after SES deployment occurs infrequently.

Incidence of side-effects of ticlopidine after sirolimus-eluting stent implantation.

BACKGROUND: Because of its side-effects, long-term administration of ticlopidine limits the use of the sirolimus-eluting stent (SES) in Japan. METHODS AND RESULTS: Side-effects of ticlopidine occurred in 41 (9.3%) of 440 patients who underwent SES implantation. The majority were liver dysfunction (4.5%) and rash (3.6%). One patient died from severe liver dysfunction. Neutropenia occurred in 3 patients (0.7%). It is remarkable that 28% of side-effects occurred >8 weeks after the initiation of ticlopidine. CONCLUSIONS: Ticlopidine has a relative high rate of side-effects. Clopidogrel should be approved for prevention of stent thrombosis as soon as possible.