Prognostic value of initial serum sodium level in predicting disease severity in patients with COVID-19: A multicenter retrospective study.

INTRODUCTION: Early prediction of coronavirus disease (COVID-19) severity is crucial. Hyponatremia has been linked to poor outcomes in hospitalized COVID-19 patients, but its association with mild cases is unclear. This study aimed to investigate whether initial serum sodium level is a risk factor for COVID-19 severity in patients with mild-to-moderate disease. METHODS: A multicenter retrospective cohort study was conducted in 10 hospitals in Fukui City, Japan, from July 1, 2020, to October 31, 2021. The study included 1055 adult patients with asymptomatic, mild, or moderate COVID-19 confirmed by a positive RT-PCR test. The primary outcome was the need for oxygen therapy after hospitalization, and the secondary outcome was the composite of in-hospital death and critical care interventions. The association between initial serum sodium level (at the emergency department or on admission) and outcomes was examined, adjusting for age, sex, hypertension, and pneumonia presence. RESULTS: Of the 1267 patients diagnosed with COVID-19 during the study period, 1055 were eligible (median age: 45 years; 54 % male). Hyponatremia was observed in 5.2 % of patients upon admission. A lower initial serum sodium level was associated with an increased risk of the need for oxygen therapy after hospitalization (adjusted odds ratio [OR] per 1 mmol/L lower, 1.12 [95 % confidence interval {CI}, 1.05-1.19]) and the composite of critical care and in-hospital death (adjusted OR per 1 mmol/L lower, 1.09 [95 % CI, 0.99-1.20]). CONCLUSIONS: Among patients with mild COVID-19, lower initial serum sodium level was a risk factor for COVID-19 progression.

Long-Term (>10 Years) clinical outcomes of first-in-human biodegradable poly-l-lactic acid coronary stents: Igaki-Tamai stents.

BACKGROUND: The purpose of this study was to evaluate the long-term safety of the Igaki-Tamai stent, the first-in-human fully biodegradable coronary stent made of poly-l-lactic acid. METHODS AND RESULTS: Between September 1998 and April 2000, 50 patients with 63 lesions were treated electively with 84 Igaki-Tamai stents. Overall clinical follow-up (>10 years) of major adverse cardiac events and rates of scaffold thrombosis was analyzed together with the results of angiography and intravascular ultrasound. Major adverse cardiac events included all-cause death, nonfatal myocardial infarction, and target lesion revascularization/target vessel revascularization. During the overall clinical follow-up period (121 ± 17 months), 2 patients were lost to follow-up. There were 1 cardiac death, 6 noncardiac deaths, and 4 myocardial infarctions. Survival rates free of all-cause death, cardiac death, and major adverse cardiac events at 10 years were 87%, 98%, and 50%, respectively. The cumulative rates of target lesion revascularization (target vessel revascularization) were 16% (16%) at 1 year, 18% (22%) at 5 years, and 28% (38%) at 10 years. Two definite scaffold thromboses (1 subacute, 1 very late) were recorded. The latter case was related to a sirolimus-eluting stent, which was implanted for a lesion proximal to an Igaki-Tamai stent. From the analysis of intravascular ultrasound data, the stent struts mostly disappeared within 3 years. The external elastic membrane area and stent area did not change. CONCLUSION: Acceptable major adverse cardiac events and scaffold thrombosis rates without stent recoil and vessel remodeling suggested the long-term safety of the Igaki-Tamai stent.

Differences in early-phase tracer distribution in lung between 11C-acetate and 13N-ammonia.

AIM: N-ammonia and C-acetate are well-known tracers useful for the measurement of myocardial blood flow. Some studies reported that the measurement of C-acetate showed better statistical quality than that with N-ammonia. To evaluate this difference, we focused on the early-phase tracer kinetics in blood and lung. The tracer kinetics in the myocardium, arterial blood, venous blood, and lung were compared between these two tracers. PATIENTS AND METHODS: Twelve patients were studied. Dynamic positron emission tomography was performed with C-acetate and N-ammonia within a 1-week period. The time activity curves (TACs) of the myocardium, arterial blood, and lung were calculated. The TACs normalized to the peak activity of right ventricle blood (normalized TAC) were also generated. RESULTS: The area under the curve of each TAC was calculated. Lung activity tended to be higher when assessed with N-ammonia. The area under the curve of the lung was larger with N-ammonia than with C-acetate both with the original TAC (478+/-232 vs. 248+/-87 MBq s/ml, P<0.001) and the normalized TAC (47.1+/-17.9 vs. 22.8+/-6.9 ratio x s, P<0.001). CONCLUSION: N-ammonia and C-acetate showed strikingly different early-phase tracer distribution in the lung. This difference may affect myocardial blood flow measurement, which largely depends on the early-phase image quality.

Simple quantification of myocardial perfusion by pixel-by-pixel graphical analysis using carbon-11 acetate: comparison of the K-complexes of carbon-11 acetate and nitrogen-13 ammonia.

AIM: The aim of this study was to evaluate the measurement of myocardial blood flow (MBF) and develop a method for producing parametric perfusion images with carbon-11 (11C-)acetate by a simple graphical analysis method. PATIENTS AND METHODS: A total of 14 patients underwent dynamic PET acquisition using nitrogen-13 (13N-)ammonia and 11C-acetate at rest to measure the influx rate constants of the tracers (K*amm and K*ace, respectively). Using the early phase of dynamic data (30-150 s), K*amm and K*ace were calculated pixel-by-pixel by the graphical analysis method. RESULTS: The patients were divided into two groups (groups A and B). The regression equation relating K*amm and K*ace was calculated with group A. K*amm and K*ace were linearly correlated (r2=0.718, P<0.001). The regression equation was K*ace=0.736.K*amm+0.086. By using this equation, K*ace was converted into MBFace. To validate this equation, MBFace and MBF measured with 13N-ammonia (MBFamm) in group B were compared. MBFamm and MBFace exhibited a good linear correlation. The regression line was very close to the line of identity (MBFace=1.01.MBFamm +0.01, r2=0.838, P<0.001). The image quality of MBFace was generally better than that of MBFamm. CONCLUSION: Using the graphical analysis method, it is convenient and reliable to measure myocardial perfusion and develop parametric images with 11C-acetate under resting conditions.

Histopathological findings of new in-stent lesions developed beyond five years.

We analyzed 14 cases of new lesions inside implanted bare-metal stents. In every case, there was no angiographic restenosis within 3 years, but a new lesion was observed inside a stented segment at long-term follow-up (>5 years). Fourteen cases were evaluated: 9 with Wiktor stents, 2 with Palmaz-Schatz stents, and 3 with ACS Multilink stents. The interval from stent implantation to follow-up angiography was 63-147 months (89 +/- 23). Thirteen lesions were treated by percutaneous coronary intervention (PCI) and stenotic tissue was obtained by directional coronary atherectomy (DCA) in 10 cases. All retrieved samples were composed of newly developed atherosclerosis facing the healed neointimal layer, and four samples showed histopathological findings of acute coronary syndrome. Stent struts were retrieved in four cases and no inflammation was observed surrounding them. Qualitative and quantitative analysis of stent struts was performed in two cases that showed no metal corrosion. These findings suggest that new atherosclerotic progression occurred inside the implanted stent without peristrut inflammation.

Serial angioscopic findings after successful intracoronary brachytherapy for in-stent restenosis.

The intracoronary changes that occur after brachytherapy for in-stent restenosis (ISR) have yet to be fully established. The purpose of this study in patients who had ISR was to examine the serial angioscopic changes in intracoronary lesions that occurred after brachytherapy. Forty-four patients who had ISR (49 lesions) underwent balloon angioplasty (n = 34) or directional atherectomy (n = 15), followed by intracoronary brachytherapy using a beta-emitting phosphorus-32 source wire. Angioscopic investigations were performed 3 and 9 months after brachytherapy. Uncovered stents were detected in 63.3% of lesions at 3 months. A significant decrease (p = 0.028) in this prevalence occurred over the next 6 months, with 36% of lesions having uncovered stents at 9 months. At 3 months, 33% of the lesions had visible erosion or ulceration and superficial thrombus. The prevalence of these characteristics was decreased at 9 months, although 17% of the lesions were still ulcerated or eroded at that time. Protruding thrombus was not observed in any lesion at 3 and 9 months. In conclusion, uncovered stents and intimal erosions or ulcerations were still present 9 months after brachytherapy in 36% and 17% of lesions, respectively. These results suggest that the healing process was not completed 9 months after brachytherapy in approximately 33% of lesions.

Predictors of improvement in left ventricular function after initially successful angioplasty of unprotected left main coronary artery stenoses.

BACKGROUND: Percutaneous coronary intervention (PCI) has been increasingly applied to unprotected left main coronary artery (LMCA) lesions, with varied procedural success and clinical outcomes. However, the effect of PCI on left ventricular performance is still unclear, and there are no clinical studies assessing factors that influence left ventricular ejection fraction (LVEF) in these cases. METHODS: Between April 1986 and August 2002, de novo PCI was performed for unprotected LMCA stenoses in 199 patients. Close clinical and angiographic follow-up were conducted after the procedure. RESULTS: One hundred eighty patients survived over six months and analysis of paired left ventriculography was possible in 175 patients. Improvement in LVEF was observed in the entire population (52.9 +/- 15.7% to 56.1 +/- 14.3%, p = 0.048). The LVEF change was 6.7 +/- 9.5% (p < 0.01) in group with baseline LVEF < or = 50% and 0.7 +/- 6.7 % (p = NS) in group with LVEF > 50%. There was significant intergroup difference (p < 0.001). Patients with baseline diameter stenosis > or = 60% had an improvement of 5.3 +/- 8.3% (p < 0.05) whereas those with stenosis < 60% had no improvement (2.0 +/- 8.4%, p = NS). CK-MB elevation > or = 3 times normal after PCI had a significant inverse association with improvement in LVEF (p < 0.05). Multivariate analysis revealed baseline LVEF < or = 50% was the only independent predictor of improvement in LVEF (standard estimate = 3.509, 95% CI: 2.164-4.854, p < 0.001). CONCLUSIONS: Successful PCI procedure is associated with significant improvement in LVEF, especially in patients with depressed left ventricular function.

Intravascular ultrasound-guided directional coronary atherectomy for unprotected left main coronary stenoses with distal bifurcation involvement.

Stent implantation in unprotected left main coronary artery (LMCA) bifurcation lesions may improve procedural and late clinical outcomes. However, concerns regarding stent-related complications, such as stent jail, subacute thrombosis, and in-stent restenosis remain. Optimal debulking by directional coronary atherectomy (DCA) with intravascular ultrasound (IVUS) guidance may be effective in this complex lesion subset, but this strategy has not yet been established. Our objective was to evaluate the safety and efficacy of IVUS-guided DCA for unprotected LMCA stenoses with distal bifurcation involvement. A total of 67 consecutive patients were included in this study and procedural success was achieved in all cases. Two cardiac deaths (2.9%) were noted and 3 patients (4.5%) underwent repeat angioplasty during hospitalization. There was no Q-wave myocardial infarction or emergency bypass surgery. Non-Q-wave myocardial infarction (creatine kinase-MB >3 times normal) occurred in 13.4% of patients. Stent implantation was necessary in 17 cases (25.4%) to achieve an optimal result. IVUS showed an improved lumen cross-sectional area and a low plaque burden in the LMCA after intervention. All-cause mortality, angiographic restenosis, and the target lesion revascularization rates at 6 months were 7.4%, 23.8%, and 20.0%, respectively. With IVUS guidance, aggressive DCA can be performed safely in unprotected LMCA bifurcation lesions, and optimal angiographic and IVUS results can be achieved with low residual plaque burden, which leads to a low restenosis rate. Optimal lesion debulking by DCA does not necessarily need adjunctive stenting in this specific anatomic subset.

Lesion regression after percutaneous coronary intervention for unprotected left main trunk disease.

BACKGROUND: Although some studies have documented the six-month angiographic outcomes of percutaneous coronary intervention (PCI) with new devices for unprotected left main trunk disease (ULMTD), a long-term angiographic analysis is mandatory to evaluate the safety and effectiveness of this procedure. This study aims to assess a long-term (one year or more) angiographic analysis after PCI for this lesion. METHODS: PCI was performed for 225 ULMTD with de novo or restenotic lesions. There were 19 deaths and 12 repeat PCIs during the hospital stay. The remaining 194 lesions were followed, and 126 lesions showed no angiographic restenosis or target lesion revascularization within six months. Finally, long-term quantitative angiographic follow-up was completed in 78 lesions (mean 2.4 years, maximum 7.5 years after PCI). RESULTS: Minimal lumen diameter increased significantly from 2.46 +/- 0.59 mm to 2.72 +/- 0.65 mm (p < 0.0001) and percent diameter stenosis decreased significantly from 26 +/- 14% to 19 +/- 14% (p < 0.0001) between the six-month and the long-term follow-ups. No additional restenosis or new lesions were found at long-term follow-up, and significant lesion regression was ascertained in each procedure (directional coronary atherectomy, p < 0.005; ballooning, p < 0.005; stenting, p < 0.05). CONCLUSIONS: These findings support the safety and effectiveness of PCI for ULMTD during the long-term period.

New technique for superior guiding catheter support during advancement of a balloon in coronary angioplasty: the anchor technique.

To get superior guiding catheter support, we tried a new method called the anchor technique. By inflating a balloon in a nontarget vessel and holding its shaft with backward force while advancing another balloon, the anchor effect for the guiding catheter could be obtained and it appeared to be helpful for a balloon or a stent to cross the target lesion.

Biodegradable stents as a platform to drug loading.

Despite technical and mechanical improvement in coronary stents the incidence of restenosis caused by in-stent neointimal hyperplasia remains high. Oral administration of numerous pharmacological agents has failed to reduce restenosis after coronary stenting in humans, possibly owing to insufficient local drug concentration. Therefore, drug-eluting stents were developed as a vehicle for local drug administration. The authors developed a new drug-eluting polymer stent that is made of poly-l-lactic acid polymer mixed with tranilast, an anti-allergic drug that inhibits the migration and proliferation of vascular smooth muscle cells induced by platelet-derived growth factor and transforming growth factor->1. Polymer stents might be superior to polymer-coated metallic stents as local drug delivery stents in terms of biodegradation and the amount of loaded drug. Drug-mixed polymer stents can be loaded with a larger amount of drug than can drug-coated metallic stents because the polymer stent struts can contain the drug. Clinical application is required to assess the safety and efficacy of drug-eluting polymer stents against stent restenosis.

Quantitative evaluation of myocardial blood flow and ejection fraction with a single dose of (13)NH(3) and Gated PET.

UNLABELLED: To evaluate myocardial blood flow (MBF) and cardiac function with a single dose of (13)NH(3), electrocardiographically (ECG) gated PET acquisition was performed after a dynamic PET scan was obtained. Gated blood-pool (GBP) imaging with C(15)O PET was also performed to compare the left ventricular ejection fraction (LVEF) obtained using the 2 methods. METHODS: Six healthy volunteers and 34 patients with cardiovascular disease were studied. Each subject underwent dynamic PET scanning after a slow intravenous injection of approximately 740 MBq (13)NH(3), followed by ECG gated PET scanning. MBF images were calculated by the Patlak plot method. Before obtaining the (13)NH(3) scan, the GBP image was obtained with a bolus inhalation of C(15)O. Twenty patients also underwent left ventriculography (LVG) to compare the value of the LVEF obtained using this technique with that determined using the gated PET method. RESULTS: The mean regional value of MBF calculated for healthy volunteers in the resting condition was 0.61 +/- 0.10 mL/min/g. The LVEF obtained using GBP PET (EF(CO)) was consistent with that obtained using LVG. The LVEF calculated from gated (13)NH(3) scans (EF(NH3)) correlated well with EF(CO), although EF(NH3) slightly underestimated the LVEF (EF(NH3) = 0.97. EF(CO) - 2.94; r = 0.87). EF(NH3) was significantly different from EF(CO) in patients with a perfusion defect in the cardiac wall (EF(NH3) = 39% +/- 11% vs. EF(CO) = 45% +/- 11%; n = 19; P < 0.001), whereas no significant difference was found between them in subjects with no defect (EF(NH3) = 58% +/- 13% vs. EF(CO) = 61% +/- 10%; n = 21). CONCLUSION: Gated PET acquisition accompanied by obtaining a dynamic PET scan with a single dose of (13)NH(3) is a promising method for the simultaneous clinical evaluation of MBF and cardiac function. However, in patients with a defect in the cardiac wall, EF(NH3) showed a tendency to underestimate the EF compared with EF(CO).

Comparison of the self-expanding Radius stent and the balloon-expandable Multilink stent for elective treatment of coronary stenoses: a serial analysis by intravascular ultrasound.

We compared the outcome of the self-expanding Radius stent and the balloon-expandable Multilink stent serially by angiography and intravascular ultrasound. Successful stent deployment was achieved in 66 lesions of 56 stable angina patients (34 lesions with Radius stents and 32 lesions with Multilink stents). At follow-up, there were no significant differences in minimal lumen diameter or percent diameter stenosis between the groups, nor in restenosis rates, although the Radius stent group rate was slightly lower (23.5% vs. 31.3%). In the Radius stent group, stent cross-sectional area (CSA) increased gradually after implantation until the 6-month follow-up (8.37 +/- 1.83 to 10.16 +/- 2.59 mm(2); n = 15), giving a larger CSA (P = 0.03) than the Multilink stent group, which decreased (9.00 +/- 2.05 to 8.27 +/- 2.15 mm(2); n = 17). The lumen CSA was also slightly larger (6.82 +/- 3.06 vs. 5.84 +/- 1.85 mm(2); P = 0.29) in the Radius stent group. These findings indicated that the Radius stent enlarged progressively after implantation, which might be useful for prevention of restenosis.

Biodegradable Polymeric Stents.

To overcome several problems of conventional metallic stents, there have been many attempts to manufacture stents made of biodegradable materials. Although some studies have noted various degrees of inflammatory responses after biodegradable stent implantation, stents made of poly-l-lactic acid (PLLA) showed high biocompatibility with minimal inflammatory response and neointimal formation in porcine coronary arteries. Therefore, PLLA materials are more likely to cover the specific need for human coronary arteries in terms of biodegradation period and scaffolding ability over 6 months. A clinical study of PLLA self-expanding stent implantation is underway in Japan. The initial and 6-month results are favorable and suggest the feasibility, safety, and efficacy of the PLLA biodegradable stent in humans. However, long-term follow-up with larger numbers of patients will be required to validate the long-term efficacy of PLLA stents.