A Low Arginine/Ornithine Ratio is Associated with Long-Term Cardiovascular Mortality.

AIMS: The long-term prognostic value of the bioavailability of L-arginine, an important source of nitric oxide for the maintenance of vascular endothelial function, has not been investigated fully. We therefore investigated the relationship between amino acid profile and long-term prognosis in patients with a history of standby coronary angiography. METHODS: We measured the serum concentrations of L-arginine, L-citrulline, and L-ornithine by high-speed liquid chromatography. We examined the relationship between the L-arginine/L-ornithine ratio and the incidence of all-cause death, cardiovascular death, and major adverse cardiovascular events (MACEs) in 262 patients (202 men and 60 women, age 65±13 years) who underwent coronary angiography over a period of ≤ 10 years. RESULTS: During the observation period of 5.5±3.2 years, 31 (12%) patients died, including 20 (8%) of cardiovascular death, while 32 (12%) had MACEs. Cox regression analysis revealed that L-arginine/L-ornithine ratio was associated with an increased risk for all-cause death (unadjusted hazard ratio, 95% confidence interval) (0.940, 0.888-0.995) and cardiovascular death (0.895, 0.821-0.965) (p＜0.05 for all). In a model adjusted for age, sex, hypertension, hyperlipidemia, diabetes, current smoking, renal function, and log10-transformed brain natriuretic peptide level, cardiovascular death (0.911, 0.839-0.990, p=0.028) retained an association with a low L-arginine/ L-ornithine ratio. When the patients were grouped according to an L-arginine/L-ornithine ratio of 1.16, the lower L-arginine/L-ornithine ratio group had significantly higher incidence of all-cause death, cardiovascular death, and MACEs. CONCLUSION: A low L-arginine/L-ornithine ratio may be associated with increased 10-year cardiac mortality.

Association of serum nitric oxide metabolite level with mortality in patients undergoing coronary angiography.

BACKGROUND: Nitric oxide (NO) is a relevant molecule for vascular homeostasis. The level of serum NO metabolites (NOx), which consist of nitrite and nitrate, has been investigated as an alternative biomarker of NO production, but its clinical value has not yet been determined. METHODS AND RESULTS: 143 patients (66 ±â€¯12 years old) were followed up after coronary catheterization. During a median (inter-quartile range) observation period of 6.13 (3.32-9.21) years, there were 20 (14 %) all-cause deaths, including 11 (8 %) cardiovascular deaths, 17 (12 %) major adverse cardiovascular events, and 17 (12 %) hospital admissions for heart failure. Median NOx level was 34.5 µmol/L (23.9-54.3). NOx was a risk factor for all-cause death [hazard ratio (HR) by unit increase, 1.010, 95 % confidence interval (CI) 1.001-1.018; p = 0.021] and heart failure (HR 1.010, CI 1.001-1.019; p = 0.029). Even after adjustment for age, sex, coronary risk factors, C-reactive protein, log-transformed brain natriuretic peptide, estimated glomerular filtration rate, and nitrate treatment, NOx was a risk factor for all-cause death (HR 1.015, CI 1.004-1.027; p = 0.008) and admission with heart failure (HR 1.018, CI 1.005-1.018, p = 0.007). CONCLUSIONS: An increase in serum NOx level does not herald a benign clinical course but is an independent predictor of high risk of any-cause mortality and heart failure.

Effectiveness of the d-ROMs oxidative stress test to predict long-term cardiovascular mortality.

BACKGROUND: The long-term prognostic value of the derivatives of reactive oxidative metabolites (d-ROMs) oxidative stress test, which measures hydroperoxide in blood, has not been fully investigated. METHODS AND RESULTS: We administered the d-ROMs test to 265 patients with cardiovascular disease (204 men, 61 women; age, 65 ± 13 years) and followed these patients for up to 10 years. During the observational period of 5.82 (2.47-8.34) years, 31 (12%) patients died, including 20 (8%) of cardiovascular death, and 33 (12%) had major adverse cardiovascular events (MACEs). Cox regression analysis revealed that patients with a d-ROMs value ≥395 U.CARR had a greater risk for all-cause mortality [unadjusted hazard ratio (95% confidence interval), 3.586 (1.772-7.257)], cardiovascular death [7.034 (2.805-17.640)], and MACEs [4.440 (2.237-8.814)] (p < 0.001 for all). In a model adjusted for age, sex, estimated glomerular filtration rate, C-reactive protein, diabetes, hypertension, hyperlipidemia, coronary artery diseases, current smoking, and log-transformed brain natriuretic peptide, all-cause death [2.311 (1.059-5.135), p = 0.036], cardiovascular death [4.398 (1.599-12.099), p = 0.004], MACEs [2.696 (1.266-5.739), p = 0.010] were still significant in patients with high d-ROMS values. CONCLUSION: A high d-ROMs value is an independent predictor of the long-term risk of cardiovascular mortality. A d-ROMs value of 395 U.CARR was considered to be an appropriate threshold for distinguishing prognosis.

Effectiveness of pulsatility index of carotid Doppler ultrasonography to predict cardiovascular events.

PURPOSE: The pulsatility index (PI) obtained from carotid ultrasonography is considered to be a marker of cerebrovascular resistance. However, the impact of PI on cardiovascular events has yet to be fully addressed. METHOD: Fifty-four patients who underwent both carotid ultrasonography and coronary angiography were followed for 5.9 ± 3.2 years. The relationship between the incidence of cardiovascular events and PI was investigated. RESULT: There were 10 (19%) deaths, four (7%) cardiovascular deaths, and nine (17%) major adverse cardiovascular events (MACEs). The cardiovascular events-defined as all hospitalization for MACEs plus heart failure, revascularization, and cardiovascular surgery-occurred in 21 patients (39%). The patients were divided into two groups according to each threshold of PI value for common carotid arteries (CCA), internal carotid arteries (ICA), and external carotid arteries (ECA), respectively. The thresholds were calculated based on receiver-operating characteristic curves for cardiovascular events. Log-rank test showed that the groups with CCA-PI ≥ 1.71, ICA-PI ≥ 1.20, and ECA-PI ≥ 2.46 had a higher incidence of cardiovascular events, respectively (p < 0.05). ECA-PI ≥ 2.46 was associated with an increased incidence of MACEs. Multivariate Cox regression analysis adjusting for cardiovascular risk factors showed that high PI of CCA, ICA, or ECA was a risk factor for cardiovascular events, respectively (CCA-PI ≥ 1.71, hazard ratio (HR) 3.242, p = 0.042; ICA-PI ≥ 1.20, HR 3.639, p = 0.012; ECA-PI ≥ 2.46, HR 11.322, p = 0.001). CONCLUSION: The results suggested that carotid PIs were independent predictive factors for further cardiovascular events. In particular, high ECA-PI levels may reflect severe arteriosclerosis.

Characterization of tolvaptan response and its impact on the outcome for patients with heart failure.

BACKGROUND: Conventional diuretic therapy such as loop diuretics is a cornerstone of the treatment for heart failure (HF). Diuretic response is an important factor in determining resistance to HF therapy and has been shown to be associated with subsequent clinical outcome. Tolvaptan (TVP), a vasopressin V2 receptor antagonist, has a favorable profile in terms of rapid fluid removal and less aggravation of renal function. We hypothesized that the response to TVP might be associated with the subsequent clinical outcome. METHOD: In this single-center retrospective study, 148 consecutive HF patients who were administered TVP from 2014 through 2018 [age 79 (69-86) years, male 89 (60%)] were included. Ninety-six patients were divided into TVP responder [N = 39 (41%)] and non-responder groups based on the cut-off value of gained urine output (+ 93 ml/mg TVP /day) on the day after TVP was introduced. RESULTS: Early TVP introduction (p = 0.012) and lower dose of loop diuretics (p = 0.043) were predictors of TVP responder. For 2 years after discharge, TVP responders showed more favorable outcomes regarding the primary endpoint defined as the composite of all-cause death and HF readmission (p = 0.034, log-rank test) and HF readmission (p = 0.005). A multivariable Cox model analysis revealed that TVP responder was an independent predictor of the primary endpoint (hazard ratio 0.48, p = 0.041). TVP responders had a lower number of HF readmissions over a 1-year period (p = 0.002). TVP response was independently associated with the number of HF readmissions (p = 0.015). The proportion of patients with an extended period between discharge and HF readmission after TVP administration was higher in responders than non-responders (67% vs. 23%, p = 0.006). These associations of TVP response and post-discharge outcomes were more evident in patients who continued TVP after discharge. CONCLUSION: TVP response can be indicative of subsequent clinical outcomes and may be informative when considering advanced care planning.

Prevalence of the Academic Research Consortium high bleeding risk criteria in patients undergoing endovascular therapy for peripheral artery disease in lower extremities.

The Academic Research Consortium (ARC) recently published a definition of patients at high bleeding risk (HBR) undergoing percutaneous coronary intervention. However, the prevalence of the ARC-HBR criteria in patients undergoing endovascular therapy (EVT) for peripheral artery disease in lower extremities has not been thoroughly investigated. This study sought to investigate the prevalence and impact of the ARC-HBR criteria in patients undergoing EVT. We analyzed 277 consecutive patients who underwent their first EVT from July 2011 to September 2019. We applied the full ARC-HBR criteria to the study population. The primary end point was a composite outcome of all-cause mortality, Bleeding Academic Research Consortium 3 or 5 bleeding, and lower limb amputation within 12 months of EVT. Among the 277 patients, 193 (69.7%) met the ARC-HBR criteria. HBR patients had worse clinical outcomes compared with non-HBR patients at 12 months after EVT, including a higher incidence of the composite primary outcome (19.2% vs. 3.6%, p < 0.001) and all-cause death (7.8% vs. 0%, p = 0.007). In a multivariate Cox proportional hazards regression analysis, presence of the ARC-HBR criteria [hazard ratio (HR) 4.15, 95% confidence interval (CI) 1.25-13.80, p = 0.020], body mass index (HR 1.13, 95% CI 1.01-1.27, p = 0.042), diabetes mellitus (HR 2.70, 95% CI 1.28-5.69, p = 0.009), hyperlipidemia (HR 0.41, 95% CI 0.21-0.80, p = 0.009), and infrapopliteal lesions (HR 3.51, 95% CI 1.63-7.56, p = 0.001) were independent predictors of the primary composite outcome. Approximately 70% of Japanese patients undergoing EVT met the ARC-HBR criteria, and its presence was strongly associated with adverse outcomes within 12 months of EVT.

A case of vascular Behçet's disease complicated with acute myocardial infarction due to spontaneous coronary artery dissection.

Spontaneous coronary artery dissection (SCAD) is a rare cause of acute myocardial infarction and occurs predominantly in young women without conventional cardiovascular risk factors. Emotional or physical stress and hormone imbalance are associated with the occurrence of SCAD, but the precise mechanisms have not been sufficiently elucidated. Furthermore, there is a paucity of data regarding the underlying disease in patients with SCAD. We herein report a case involving a 48-year-old man who developed acute myocardial infarction due to SCAD in the distal segment of the left anterior descending artery and was successfully treated with conservative medical therapy. A repeat coronary angiography examination performed 2 weeks later revealed complete angiographic healing. In addition, he was treated for suspected Behçet's disease because he had a history of recurrent aphthous stomatitis, nodular erythema, and genital ulcers. After thorough assessment, he was finally diagnosed with vascular Behçet's disease based on additional evidence of bilateral deep vein thrombosis. This case report highlights a rare case of vascular Behçet's disease complicated with SCAD in a male patient. Physicians should be aware that SCAD may occur in association with systemic inflammatory disease including Behçet's disease, even in male patients. .

Successful Percutaneous Coronary Intervention Using Intravascular Ultrasound-Guided Rewiring Technique in a Case of Spontaneous Coronary Artery Dissection Involving Left Main Bifurcation.

We herein describe a 49-year-old woman without significant cardiovascular risk factors who was transferred to our hospital with sudden onset of chest pain. The patient was diagnosed with non-ST-elevation acute myocardial infarction, and coronary angiography revealed a dissection at the proximal site of the left anterior descending artery (LAD) extending from the left main trunk (LMT) suggestive of spontaneous coronary artery dissection (SCAD). Because coronary flow was impaired after contrast injection and the patient had chest pain with ST elevation, urgent percutaneous coronary intervention was performed. The first guide wire was initially introduced from the LMT to the distal LAD, but intravascular ultrasound (IVUS) imaging revealed that the guide wire had passed through the true lumen of the left coronary artery ostium, false lumen at the ostium of the left circumflex artery, and true lumen of the distal LAD. We then reinserted another guide wire using an IVUS-guided rewiring technique from the true lumen of the LMT to the distal LAD. Finally, a drug-eluting stent was deployed to cover the dissected segment, and final coronary angiography revealed acceptable results with a patent left circumflex artery. This case report highlights that physicians should consider SCAD among the differential diagnoses in patients presenting with acute coronary syndrome, particularly in young women. In the present case, IVUS played a pivotal role in not only detecting the arterial dissection but also correctly introducing the guide wire into the true lumen.

Stent Deformation Caused by Entrapment of the Side Branch Balloon Catheter During the Jailed Balloon Protection Technique for a Calcified Coronary Bifurcation Lesion: A Case Report and Literature Review.

Percutaneous coronary intervention (PCI) for true bifurcation lesions is challenging. Although the jailed balloon protection technique is an established method with which to prevent side branch occlusion during the treatment of bifurcation lesions, little is known regarding the potential risks of this technique. We describe a 71-year-old man with exertional angina pectoris who was treated with PCI for a calcified true bifurcation lesion in the left anterior descending artery and diagonal branch. After performing rotational atherectomy (1.75 mm burr) for the main vessel and pre-dilatation for both the main vessel and side branch, we performed the jailed balloon technique to protect the large diagonal branch during stent implantation. However, the jailed balloon was entrapped after main vessel stent balloon inflation. The entrapped jailed balloon was then inflated again and successfully removed after balloon deflation, but significant stent deformation was seen with intravascular ultrasound imaging. Fortunately, post-dilatation was successfully performed with a non-compliant balloon, and a final coronary angiogram showed acceptable results. This case report and literature review highlights a potential risk of the jailed balloon technique and conceivable alternatives during PCI for true bifurcation lesions.