Current Status of Contrast Computed Tomography Examination for Diagnosing Acute Pulmonary Thromboembolism.

The purpose of this study was to identify instances of unnecessary contrast-enhanced computed tomography (CT) scans performed at the time of diagnosis in patients with pulmonary thromboembolism at the emergency department of Saiseikai Kumamoto Hospital in Kumamoto Prefecture, Japan, between April 1, 2015, and March 31, 2020. The decision criteria for unnecessary contrast-enhanced CT scans included a Wells score of low or moderate risk, a D-dimer level <1.0 µg/mL, and no shock symptoms, or a negative finding for pulmonary thromboembolism. Consequently, 27 patients were considered to have undergone unnecessary contrast-enhanced CT scans. This equated to approximately 15.6% of the study population.

Impact of extracorporeal CPR with transcatheter heart pump support (ECPELLA) on improvement of short-term survival and neurological outcome in patients with refractory cardiac arrest - A single-site retrospective cohort study.

Aim: Extracorporeal cardiopulmonary resuscitation (E-CPR) using veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a novel lifesaving method for refractory cardiac arrest. Although VA-ECMO preserves end-organ perfusion, it may affect left ventricular (LV) recovery due to increased LV load. An emerging treatment modality, ECPELLA, which combines VA-ECMO and a transcatheter heart pump, Impella, can simultaneously provide circulatory support and LV unloading. In this single-site cohort study, we assessed impact of ECPELLA support on clinical outcomes of refractory cardiac arrest patients. Method: We retrospectively reviewed 165 consecutive cardiac arrest patients, who underwent E-CPR by VA-ECMO with or without intra-aortic balloon pump (IABP) or ECPELLA from January 2012 to September 2021. We assessed 30-day survival rate, neurological outcome, hemodynamic data, and safety profiles including hemolysis, acute kidney injury, blood transfusion and embolic cerebral infarction. Results: Among 165 E-CPR patients, 35 patients were supported by ECPELLA, and 130 patients were supported by conventional VA-ECMO with or without IABP. Following propensity score matching of 30 ECPELLA and 30 VA-ECMO patients, the 30-day survival (ECPELLA: 53%, VA-ECMO: 20%, p < 0.01) and favorable neurological outcome determined by the Cerebral Performance Category score 1 or 2 (ECPELLA: 33%, VA-ECMO: 7%, p < 0.01) were significantly higher with ECPELLA. Patients receiving ECPELLA also showed significantly higher total mechanical circulatory support flow and lower arterial pulse pressure for the first 3 days (p < 0.01) of treatment. There were no statistical differences in safety profiles between treatment groups. Conclusion: ECPELLA may be associated with improved 30-day survival and neurological outcome in patients with refractory cardiac arrest.

Predictors of hypoxemia in type-B acute aortic syndrome: a retrospective study.

Acute aortic syndrome (AAS) can be life-threatening owing to a variety of complications, and it is managed in the intensive care unit (ICU). Although Stanford type-B AAS may involve hypoxemia, its predictors are not yet clearly understood. We studied clinical factors and imaging parameters for predicting hypoxemia after the onset of type-B AAS. We retrospectively analyzed patients diagnosed with type-B AAS in our hospital between January 2012 and April 2020. We defined hypoxemia as PaO2/FiO2 ≤ 200 within 7 days after AAS onset and used logistic regression analysis to evaluate prognostic factors for hypoxemia. We analyzed 224 consecutive patients (140 males, mean age 70 ± 14 years) from a total cohort of 267 patients. Among these, 53 (23.7%) had hypoxemia. The hypoxemia group had longer ICU and hospital stays compared with the non-hypoxemia group (median 20 vs. 16 days, respectively; p = 0.039 and median 7 vs. 5 days, respectively; p < 0.001). Male sex (odds ratio [OR] 2.87; 95% confidence interval [CI] 1.24-6.63; p = 0.014), obesity (OR 2.36; 95% CI 1.13-4.97; p = 0.023), patent false lumen (OR 2.33; 95% CI 1.09-4.99; p = 0.029), and high D-dimer level (OR 1.01; 95% CI 1.00-1.02; p = 0.047) were independently associated with hypoxemia by multivariate logistic analysis. This study showed a significant difference in duration of ICU and hospital stays between patients with and without hypoxemia. Furthermore, male sex, obesity, patent false lumen, and high D-dimer level may be significantly associated with hypoxemia in patients with type-B AAS.

Microscopic polyangiitis associated with subarachnoid hemorrhage.

Microscopic polyangiitis (MPA), an anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, is a systemic disease that damages all organs through predominantly affecting small vessels. However, few cases of MPA are related to aneurysms on medium-sized muscular vessels, and whether subarachnoid hemorrhage (SAH) is associated with MPA is still unclear. An 85-year-old woman with rapid progressive glomerular nephritis caused by MPA complained of sudden severe headache due to SAH 2 days after admission and subsequently underwent surgery. Cerebrovascular disease occurring simultaneously with MPA might result in poor prognosis, and the complications exacerbate the condition and lead to high mortality; thus, physicians should pay more attention to cerebral aneurysms concurrent with MPA. Among patients with MPA, it is important to identify priority cases and investigate the intracranial vessel environment. To the best of our knowledge, this is a rare report about SAH associated with MPA. We recommend that the presence of cerebrovascular disease should be considered in patients with MPA to improve their prognosis.

Diagnostic utility of cardiac troponin T level in patients with cardiac amyloidosis.

AIM: The aim of this study was to evaluate the diagnostic utility of high-sensitivity cardiac troponin T (hs-cTnT) levels in discriminating cardiac amyloidosis from patients with cardiac hypertrophy caused by aetiologies other than cardiac amyloidosis. METHODS AND RESULTS: Serum hs-cTnT levels were measured in 96 patients with cardiac amyloidosis (light chain: 23, wild-type transthyretin amyloidosis: 40, and mutated transthyretin amyloidosis: 33), and 91 patients with other causes of cardiac hypertrophy who were confirmed to have no cardiac amyloidosis by endomyocardial biopsy (control group). The diagnostic utility and cut-off value of hs-cTnT were evaluated by receiver operating characteristic analysis. The median hs-cTnT levels were higher in cardiac amyloidosis than the control group [0.048 (0.029-0.073) vs. 0.016 (0.010-0.031) ng/mL; P < 0.001]. High levels of hs-cTnT were suggestive of cardiac amyloidosis (cut-off value: 0.0312 ng/mL, sensitivity: 0.74, specificity: 0.76, area under the curve: 0.788; 95% confidence interval: 0.723-0.854, P < 0.001), compared with brain natriuretic peptide and E/e' ratio. The hs-cTnT levels were also useful in differentiating each type of amyloidosis from the control group. Multivariate analysis identified log hs-cTnT as an independent diagnostic factor for cardiac amyloidosis (odds ratio: 2.22; 95% confidence interval: 1.30-3.80; P = 0.004). CONCLUSIONS: High serum levels of hs-cTnT are highly suggestive of cardiac amyloidosis, allowing its differentiation from cardiac hypertrophy of other aetiologies. Further refined diagnostic approaches that include imaging modalities and histopathological examination are needed for these patients to avoid underdiagnosis of cardiac amyloidosis.

Late gadolinium enhancement on cardiac magnetic resonance imaging is associated with coronary endothelial dysfunction in patients with dilated cardiomyopathy.

Myocardial fibrosis and coronary endothelial dysfunction are important determinants of outcome in patients with heart failure. However, the relationship of these factors in patients with dilated cardiomyopathy (DCM) is not fully understood. This study aimed to investigate the relationship between endothelium-dependent coronary vasomotor abnormality and late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) in patients with DCM. We examined 38 consecutive patients with DCM. All patients underwent CMR and the acetylcholine (ACh) provocation test using cardiac catheterization. During the ACh provocation test, we sampled blood simultaneously from the coronary sinus and aortic root to compare lactate concentrations, and quantified coronary blood flow volume using an intracoronary Doppler-tipped guidewire. LGE was detected in 17 (44.7%) patients. The lactate extraction ratio (LER) in the ACh provocation test was significantly decreased in the LGE-positive group (before vs after ACh, 18.6 ± 13.6 vs - 13.3 ± 24.8%; p < 0.001) and in the LGE-negative group (before vs after ACh, 14.2 ± 19.5 vs 3.3 ± 16.2%; p = 0.02). The rate of patients with an LER < 0% (indicating myocardial lactate production due to myocardial ischemia) was significantly higher in the LGE-positive group than in the LGE-negative group [12 (70.6%) vs 7 (33.3%); p = 0.02]. Multivariable logistic regression analysis showed that a post-ACh LER < 0% was a significant predictor of LGE positivity (odds ratio 7.75; 95% confidence interval 1.37-43.68; p = 0.02). In conclusion, ACh-provoked coronary vasomotor abnormality is associated with myocardial fibrosis in patients with DCM. These results suggest that coronary endothelial dysfunction is involved in myocardial fibrosis and worsening heart failure concomitant with DCM.

Clinical significance of brachial-ankle pulse-wave velocity in patients with heart failure with preserved left ventricular ejection fraction.

BACKGROUND: Although pulse-wave velocity (PWV) is a recognized risk predictor for cardiovascular diseases, its association with cardiovascular outcomes in heart failure with preserved left ventricular ejection fraction (HFpEF) is unclear. METHODS AND RESULTS: The 502 patients with HFpEF finally enrolled in this study (mean follow-up duration: 1017 days) were divided into those with or without peripheral artery disease (PAD). The latter were further grouped according to brachial-ankle PWV (baPWV) quintiles using an ankle-brachial pressure index device. Kaplan-Meier analysis revealed a significantly higher risk of all-cause mortality and total cardiovascular events (both P = 0.01) in HFpEF patients with than without PAD. Multivariate Cox hazard analysis, including predictors identified as significant by simple Cox hazard analysis, identified PAD as a significant and independent predictor of cardiovascular events (hazard ratio: 1.85; 95% confidence interval: 1.01-3.39; P = 0.04). In an analysis of HFpEF patients without PAD grouped according to baPWV quintiles, estimated glomerular filtration rate (r = 0.21, P < 0.01) and hemoglobin (r = 0.18, P = 0.01) levels correlated negatively with baPWV. In the Kaplan-Meier analysis, patients with a baPWV more than 1900 cm/s and those with the lowest baPWV (<1300 cm/s) had a significantly higher frequency of total cardiovascular events than patients with 1300 baPWV or less which is less than 1900, indicating a J-shaped association between baPWV and total cardiovascular events as well as similarities to HFpEF patients with PAD. By contrast, the lowest baPWV group had the highest risk of heart failure-related events, accompanied by the highest brain natriuretic peptide levels. CONCLUSION: Identifying complications of PAD and measuring baPWV values in HFpEF patients can improve risk stratification.

Direct Oral Anticoagulants Form Thrombus Different From Warfarin in a Microchip Flow Chamber System.

Direct oral anticoagulants (DOACs) have low risk of intracranial hemorrhage compared to warfarin. We sought to clarify the different mechanisms responsible for suppression of bleeding events using the Total Thrombus-formation Analysis System (T-TAS), a flow-microchip chamber with thrombogenic surfaces. Blood samples were obtained at Off- and On-anticoagulant (trough) from 120 consecutive patients with atrial fibrillation (warfarin; n = 29, dabigatran; n = 19, rivaroxaban; n = 47, apixaban; n = 25), which were used for T-TAS to compute the area under the curve (AUC) (AR10-AUC30) in the AR chip, and to measure plasma concentrations of DOACs at On-anticoagulant. In addition, the two-dimensional area covered by thrombi (%) in the capillary was analyzed every 3 minutes after sample applications. The AR10-AUC30 correlated weakly and negatively with plasma concentrations of DOACs, and the levels at On-anticoagulant were lower in all groups than at Off-anticoagulant. AR10-AUC30 levels at Off- and On-anticoagulant were identical among the groups. The thrombi areas in early phase were significantly larger in rivaroxaban and apixaban than warfarin and dabigatran groups. The findings suggested that visual analysis of the AR-chip can identify the differential inhibitory patterns of warfarin and DOACs on thrombus formation under flow condition.

Cardiovascular magnetic resonance myocardial T1 mapping to detect and quantify cardiac involvement in familial amyloid polyneuropathy.

OBJECTIVES: This study sought to explore the potential role of non-contrast T1 mapping for the detection and quantification of cardiac involvement in familial amyloid polyneuropathy (FAP). METHODS: Japanese patients with FAP [n = 41, age 53.2 ± 13.9 years, genotype Val30Met (n = 25), non-Val30Met (n = 16)] underwent cardiac magnetic resonance imaging that included T1 mapping (saturation-recovery method) and late gadolinium-enhanced (LGE) imaging on a 3.0-T MR scanner. Their native T1 was measured on mid-ventricular short-axis images and compared with 30 controls. RESULTS: Of the 41 FAP patients 29 were LGE positive. The native T1 was significantly higher in FAP patients than in the controls (1,634.1 ± 126.3 ms vs. 1,432.4 ± 69.0 ms, p < 0.01), significantly higher in LGE-positive- than LGE-negative FAP patients (1,687.1 ± 104.4 ms vs. 1,505.4 ± 68.5 ms, p < 0.01), and significantly higher in LGE-negative FAP patients than the controls (p < 0.01). A native T1 cutoff value of 1,610 ms yielded 85.4% accuracy for identifying LGE-positive FAP. The native T1 significantly correlated with the interventricular septum wall thickness, the left ventricular mass, the LGE volume, the plasma B-type natriuretic peptide level, and the E/e' ratio (all p < 0.01). CONCLUSION: T1 mapping is of high diagnostic accuracy for the detection of LGE-positive FAP. The native myocardial T1 may be correlated with the severity of cardiac amyloid deposition. KEY POINTS: • The native T1 was higher in FAP patients than the controls. • The native T1 was higher in LGE-positive- than LGE-negative FAP patients. • The native T1 was higher in LGE-negative FAP patients than the controls. • The native T1 correlated with clinical markers of systolic and diastolic dysfunction. • Myocardial T1 mapping is of high diagnostic accuracy for detecting LGE-positive FAP.

Identification and Assessment of Cardiac Amyloidosis by Myocardial Strain Analysis of Cardiac Magnetic Resonance Imaging.

BACKGROUND: We explored the usefulness of myocardial strain analysis on cardiac magnetic resonance imaging (CMR) scans for the identification of cardiac amyloidosis.Methods and Results:The 61 patients with systemic amyloidosis underwent 3.0-T CMR, including CMR tagging and late-gadolinium enhanced (LGE) imaging. The circumferential strain (CS) of LGE-positive and LGE-negative patients was measured on midventricular short-axis images and compared. Logistic regression modeling of CMR parameters was performed to detect patients with LGE-positive cardiac amyloidosis. Of the 61 patients with systemic amyloidosis 48 were LGE-positive and 13 were LGE-negative. The peak CS was significantly lower in the LGE-positive than in the LGE-negative patients (-9.5±2.3 vs. -13.3±1.4%, P<0.01). The variability in the peak CS time was significantly greater in the LGE-positive than in the LGE-negative patients (46.1±24.5 vs. 21.2±20.1 ms, P<0.01). The peak CS significantly correlated with clinical biomarkers. The sensitivity, specificity, and accuracy of the diagnostic model using CS parameters for the identification of LGE-positive amyloidosis were 93.8%, 76.9%, and 90.2%, respectively. CONCLUSIONS: Myocardial strain analysis by CMR helped detect LGE-positive amyloidosis without the need for contrast medium. The peak CS and variability in the peak CS time may correlate with the severity of cardiac amyloid deposition and may be more sensitive than LGE imaging for the detection of early cardiac disease in patients with amyloidosis.

Cardioprotective Effects of LCZ696 (Sacubitril/Valsartan) After Experimental Acute Myocardial Infarction.

LCZ696 (sacubitril/valsartan) can lower the risk of cardiovascular events in chronic heart failure. However, it is unclear whether LCZ696 can improve prognosis in patients with acute myocardial infarction (MI). The present study shows that LCZ696 can prevent cardiac rupture after MI, probably due to the suppression of pro-inflammatory cytokines, matrix metalloproteinase-9 activity and aldosterone production, and enhancement of natriuretic peptides in mice. These findings suggest the mechanistic insight of cardioprotective effects of LCZ696 against acute MI, resulting in the belief that LCZ696 might be useful clinically to improve survival after acute MI.

Reduced trans-mitral A-wave velocity predicts the presence of wild-type transthyretin amyloidosis in elderly patients with left ventricular hypertrophy.

Wild-type transthyretin amyloidosis (ATTRwt) is often overlooked in elderly patients with left ventricular hypertrophy (LVH). Impaired atrial function, in addition to ventricular diastolic dysfunction, is one of the hallmarks of cardiac amyloidosis. Here, we assessed the hypothesis that atrial function evaluated by A-velocity in pulse Doppler echocardiography is useful to differentiate ATTRwt in elderly patients with LVH. We analyzed 133 consecutive patients who underwent tissue biopsy to rule out infiltrative cardiomyopathy in our institute. We excluded patients younger than 50 years, without LVH (LV thickness was less than 12 mm), with other types of cardiac amyloidosis and patients with chronic atrial fibrillation, and analyzed remaining 51 patients (ATTRwt: 16, non-ATTRwt: 35). ATTRwt patients were significantly older and had advanced heart failure compared with non-ATTRwt group. In echocardiography, E/A, E/e', and relative wall thickness was significantly higher in ATTRwt group than non-ATTRwt group. A-velocity was significantly decreased in ATTRWT group compared with non-ATTRwt group (40.8 ± 20.8 vs. 78.7 ± 28.2 cm/s, p = 0.0001). Multivariate logistic analysis using eight forced inclusion models identified trans-mitral Doppler A-wave velocity was more significant factor of cardiac amyloidosis in ATTRwt. In receiver operating characteristic (ROC) analysis, the area under the curve (AUC) for A-wave velocity in discrimination between ATTRwt and non-ATTRwt were 0.86 (CI 0.76-0.96, p < 0.001). The cut-off value was 62.5 cm/s, and it yielded the best combination of sensitivity (69.7%) and specificity (87.5%) for prediction of amyloidosis. We concluded that reduced A-velocity predicts the presence of ATTRwt in elderly patients with LVH in sinus rhythm.

Correlation between microvascular dysfunction and B-type natriuretic peptide levels in non-ischemic heart failure patients with cardiac fibrosis.

BACKGROUNDS: The relationship between microvascular dysfunction and plasma B-type natriuretic peptide (BNP) levels remains unclear in heart failure (HF) patients with cardiac fibrosis. METHODS: This study evaluated 55 consecutive non-ischemic HF patients in an effort to determine the relationship between endothelial independent coronary microvascular dysfunction and plasma BNP levels, as well as whether each measure is correlated with myocardial fibrosis. We evaluated plasma BNP levels in patients with stable HF. We used cardiac catheterization to measure trans-cardiac BNP release levels, measuring from the coronary sinus and the aortic root, and coronary flow reserve (CFR). Patients also underwent cardiac magnetic resonance imaging to evaluate for the presence of late gadolinium enhancement (LGE), as an indicator of cardiac fibrosis. RESULTS: CFR in cardiac catheterization was significantly and inversely correlated with plasma BNP levels (r=0.336, p=0.012) and trans-cardiac BNP release levels (r=0.347, p=0.041). Thirty-three patients were LGE-positive. CFR was significantly correlated with plasma BNP levels in the LGE-positive group (r=0.349, p=0.046), but this correlation was not significant in the LGE-negative group. (r=0.338, p=0.125). Multivariate logistic regression analysis revealed that a plasma BNP levels >180pg/ml at stable HF condition was significant and independent predictor of CFR<2.5 in all patients (p=0.035, odds ratio: 5.2, 95% confidence interval: 1.1-29.0), and in the LGE-positive group (p=0.040, odds ratio: 5.4, 95% confidence interval: 1.1-27.2). CONCLUSIONS: In non-ischemic HF patients especially those with cardiac fibrosis, endothelial independent microvascular dysfunction is closely correlated with plasma BNP levels, and ventricular wall tension.

A Destabilized Case of Stable Effort Angina Pectoris Induced by Low-dose Adenosine Triphosphate.

A 79-year-old man was diagnosed with sudden deafness. He had previously experienced a suspected episode of angina pectoris. At a local hospital, after 500 mg of hydrocortisone and 80 mg adenosine triphosphate (ATP) were administered, he became aware of chest discomfort. An electrocardiogram revealed serious ST-segment depressions. He was diagnosed with a non-ST elevated myocardial infarction (NSTEMI). Emergency coronary angiography revealed triple vessel disease, and the lesion was successfully stented. The mechanisms whereby the stable effort angina pectoris destabilized in this case were thought to include a reduction of the local blood flow because of an ATP product and probable thrombus formation in response to the administered steroids.

Helicobacter pylori Seropositivity in Patients with Interleukin-1 Polymorphisms Is Significantly Associated with ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Helicobacter pylori infection and interleukin-1 polymorphisms are associated with an increased risk of gastric cancer. We examined the prevalence of Helicobacter pylori seropositivity and interleukin-1 polymorphisms between ST-segment elevation myocardial infarction and non-ST-segment elevation acute coronary syndrome patients. METHODS: We recruited consecutive acute coronary syndrome patients, and 101 non-ST-segment elevation acute coronary syndrome patients and 103 ST-segment elevation myocardial infarction patients were enrolled. Interleukin-1 polymorphism analyses were performed for single nucleotide polymorphism in interleukin-1 beta-511 and the variable number of tandem repeats polymorphism in the interleukin-1 receptor antagonist by polymerase chain reaction. Immunoglobulin G antibodies against Helicobacter pylori and high sensitivity C-reactive protein were also measured. RESULTS: The rates of the simultaneous presence of interleukin-1 polymorphisms and Helicobacter pylori-seropositivity between non-ST-segment elevation acute coronary syndrome and ST-segment elevation myocardial infarction groups were 25.7% and 42.7%, respectively (P = 0.012). Helicobacter pylori-seropositive subjects with interleukin-1 polymorphisms showed significantly higher levels of high sensitivity C-reactive protein (0.04-0.12 vs. 0.02-0.05; P<0.001). Multivariate logistic regression analysis revealed that the carriage of Helicobacter pylori-seropositivity and interleukin-1 polymorphisms was significantly associated with ST-segment elevation myocardial infarction (odds ratio, 2.32; 95% confidence interval, 1.23-4.37; P = 0.009). The C-statistic of conventional risk factors was 0.68 (P<0.001) and that including Helicobacter pylori-seropositivity and interleukin-1 polymorphisms was 0.70 (P<0.001); continuous net reclassification improvement was 34% (P = 0.0094) and integrated discrimination improvement was 3.0% (P = 0.014). CONCLUSIONS: The coincidence of Helicobacter pylori-seropositivity and interleukin-1 polymorphisms was significantly associated with higher levels of high sensitivity C-reactive protein and the increased risk of ST-segment elevation myocardial infarction.

The clinical significance of plasma neopterin in heart failure with preserved left ventricular ejection fraction.

AIMS: Although inflammation plays an important role in the pathogenesis of heart failure (HF), the precise pathophysiological role of inflammation in HF with preserved left ventricular ejection fraction (HFpEF) still remains unclear. Hence, we examined the clinical significance of plasma neopterin, an inflammatory biomarker, in HFpEF patients. METHODS AND RESULTS: In the present study, we recruited consecutive HFpEF patients hospitalized in Kumamoto University Hospital, and further measured plasma neopterin by high-performance liquid chromatography and serum derivatives of reactive oxidative metabolites (DROM), a new biomarker of reactive oxygen species. Compared with risk factors (number of patients, age, sex, and equal incidence of diabetes mellitus, hypertension, and dyslipidemia) -matched non-HF patients (n = 68), plasma neopterin levels, but not serum high-sensitivity C-reactive protein levels, were significantly increased in patients with HFpEF (n = 68) (P < 0.001 and P = 0.15, respectively), accompanied by an elevation in serum DROM levels (P < 0.001). Plasma neopterin levels in New York Heart Association (NYHA) class III/IV HFpEF patients were significantly higher than in NYHA class II patients (P < 0.004). Furthermore, plasma ln-neopterin levels had significant and positive correlation with ln-DROM values (r = 0.57) and parameters of cardiac diastolic dysfunction [the ratio of early transmitral flow velocity to tissue Doppler early diastolic mitral annular velocity (r = 0.34), left atrial volume index (r = 0.17), and B-type natriuretic peptide (r = 0.38)]. Kaplan-Meier analysis showed that the high-neopterin group (>51.5 nM: median value of neopterin in HFpEF patients) had a higher probability of cardiovascular events than the low-neopterin group (log-rank test, P = 0.003). CONCLUSIONS: Plasma neopterin levels significantly increased in HFpEF and correlated with the severity of HF. Furthermore, high neopterin were significantly correlated with future cardiovascular events, indicating that measurement of plasma neopterin might provide clinical benefits for risk stratification of HFpEF patients. © 2015 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Association of CYP2C19 variants and epoxyeicosatrienoic acids on patients with microvascular angina.

Categorization as a cytochrome P450 (CYP) 2C19 poor metabolizer (PM) is reported to be an independent risk factor for cardiovascular disease. Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid by CYP2C19 epoxygenases and anti-inflammatory properties, especially in microvascular tissues. We examined the association of CYP2C19 polymorphisms and EETs on microvascular angina (MVA) caused by coronary microvascular dysfunction. We examined CYP2C19 genotypes in patients with MVA (n = 71) and healthy subjects as control (n = 71). MVA was defined as the absence of coronary artery stenosis and epicardial spasms and the presence of inversion of lactic acid levels between intracoronary and coronary sinuses in acetylcholine-provocation test or the adenosine-triphosphate-induced coronary flow reserve ratio was below 2.5. CYP2C19 PM have two loss-of-functon alleles (*2, *3). We measured serum dihydroxyeicosatrienoic acid (DHET) as representative EET metabolite. MVA group showed significantly higher CYP2C19 PM incidence (35% vs. 16%; P = 0.007) and high sense C-reactive protein (hs-CRP) levels (0.127 ± 0.142 vs. 0.086 ± 0.097 mg/dl; P = 0.043) than those of controls. Moreover, in MVA group, hs-CRP levels in CYP2C19 PM were significantly higher than that of non-PM (0.180 ± 0.107 vs. 0.106 ± 0.149 mg/dl, P = 0.045). Multivariate analysis indicated that smoking, hypertension, high hs-CRP, and CYP2C19 PM are predictive factors for MVA. In MVA group, DHET levels for CYP2C19 PM were significantly lower than that of non-PM [10.9 ± 1.64 vs. 14.2 ± 5.39 ng/ml, P = 0.019 (11,12-DHET); 15.2 ± 4.39 vs. 17.9 ± 4.73 ng/ml, P = 0.025 (14,15-DHET)]. CYP2C19 variants are associated with MVA. The decline of EET-based defensive mechanisms owing to CYP2C19 variants may affect coronary microvascular dysfunction.

Prevalence of coronary macro- and micro-vascular dysfunctions after drug-eluting stent implantation without in-stent restenosis.

BACKGROUND: The aim was to examine the prevalence and characteristics of epicardial vasomotor abnormality (EVA) and coronary microvascular dysfunction (CMD) including endothelium-dependent (EDCMD) or -independent (EICMD) in patients following a second-generation drug-eluting stent (second DES) implantation without in-stent restenosis. METHODS AND RESULTS: In 105 patients who underwent second DES implantation in the left anterior descending coronary artery (74 men; mean age, 67.9±9.6years), and in 105 suspected angina patients without stenting (65 men; mean age 66.4±9.1years), we evaluated EVA using the acetylcholine provocation test, EDCMD and EICMD by measuring the coronary flow reserve and the relationship between myocardial ischemia (intracoronary lactate production between aorta and coronary sinus and ST-T changes) or recurrent angina and vascular function. There was no difference in the incidence of EVA between DES and control (49.5% versus 55.2%; P=0.41). Given that the prevalence of CMD was higher in DES than in control (59.0% versus 29.5%; P<0.001), CMD may be associated with stent placement. Of the CMD patients, EDCMD alone, EICMD alone, and both CMDs were found in 40.3%, 22.6%, and 37.1%, respectively. Myocardial ischemia was detected in 42.4% of patients, and recurrent angina was more common in the presence of both EDCMD and EICMD in patients with EVA or CMD compared to patients with normal vascular function (EVA, 42.9% versus 7.7%, P=0.015: CMD, 39.1% versus 7.7%, P=0.007). CONCLUSIONS: Myocardial ischemia and recurrent angina may be caused by the presence of both EDCMD and EICMD after a second DES implantation without ISR.