Heterogeneity of microvascular dysfunction in women with chest pain not attributable to coronary artery disease: implications for clinical practice

Background Women with chest pain in the absence of obstructive coronary artery disease (CAD) frequently have coronary microvascular dysfunction and inducible myocardial ischemia. Microvascular dysfunction is commonly diagnosed by demonstrating abnormal flow reserve in a single coronary artery during angiography. Therefore, diagnostic accuracy is dependent on homogeneity of microvascular dysfunction in the myocardium. Methods In the Women's Ischemia Syndrome Evaluation (WISE), 34 women with chest pain and no significant CAD and 9 female control subjects underwent ¹³N-NH₃ positron emission tomography to measure adenosine-induced changes in myocardial perfusion (ie, coronary flow reserve [CFR]). Flow reserve was correlated among the left anterior descending (LAD), circumflex (LCx), and right (RCA) coronary artery distributions. Results The mean CFR in the LAD, LCx, and RCA was 2.85 ± 1.35, 2.58 ± 0.94, and 3.24 ± 1.42, respectively. Concordance in the classification of microvascular function as normal (CFR ≥2.5) versus abnormal was present in the LAD and RCA, LAD and LCx, and RCA and LCx distributions in only 71.8%, 66.7%, and 61.6% of patients, respectively. There was a modest degree of correlation of CFR between the LAD and RCA (r = 0.79, P < .001), LAD and LCx (r = 0.61, P < .001), and LCx and RCA (r = 0.57, P < .001). Comparison of CFR in the 3 coronary arteries simultaneously in all patients demonstrated that the LCx had values that were significantly lower than the RCA and LAD distributions. Conclusion Substantial discordance of classification of microvascular function among coronary artery distributions in women with chest pain and no CAD suggests that microvascular dysfunction is distributed heterogeneously in the myocardium. Assessment of CFR in a single coronary artery during cardiac catheterization may not provide an accurate assessment of the coronary microcirculation in women with chest pain not attributable to CAD. (Am Heart J 2003;145:628-35.)     

Antineutrophil cytoplasmic antibody–associated vasculitides: Could geographic patterns be explained by ambient ultraviolet radiation?

Objective

This ecological study describes and quantifies the association between ambient ultraviolet (UV) radiation levels, including daily winter vitamin D effective UV radiation levels and the incidence of the 3 antineutrophil cytoplasmic antibody–associated vasculitides (AAVs): Wegener's granulomatosis (WG), microscopic polyangiitis (MPA), and Churg‐Strauss syndrome (CSS). Latitudinal variation in occurrence of the AAVs, especially WG, has been previously reported. For other autoimmune diseases such as multiple sclerosis and type 1 diabetes mellitus, inverse associations with latitude are hypothesized to indicate a causative role for low UV radiation exposure, possibly acting via vitamin D status.

Methods

Published epidemiologic studies provided data on incident cases, total population of study regions, age‐specific incidence rates, and study location. From these data and online age‐specific population data, we calculated crude incidence rates, the expected number of cases (to control for possible age confounding), and measures of ambient UV radiation. Negative binomial regression models were used to calculate the incidence rate ratio (IRR) for a 1,000 joules/m² increase in ambient UV radiation.

Results

The incidence of WG and CSS increased with increasing latitude and decreasing ambient UV radiation, with a stronger and more consistent effect across different UV radiation measures for WG, e.g., for average daily ambient clear sky erythemal UV radiation (WG: IRR 0.64 [95% confidence interval (95% CI) 0.44–0.94], P = 0.02; CSS: IRR 0.67 [95% CI 0.43–1.05], P = 0.08; MPA: IRR 1.16 [95% CI 0.92–1.47], P = 0.22). There was no apparent latitudinal variation in MPA incidence.

Conclusion

Our findings are consistent with a protective immunomodulatory effect of ambient UV radiation on the onset of WG and CSS. We discuss possible mechanisms, including the effect of vitamin D on the immune system.     

Long‐term followup of polyarteritis nodosa,microscopic polyangiitis,and Churg‐Strauss syndrome: Analysis of four prospective trials including 278 patients

Objective

To determine the long‐term outcome of patients with polyarteritis nodosa (PAN), microscopic polyangiitis (MPA), and Churg‐Strauss syndrome (CSS), to compare the long‐term outcome with the overall French population, to evaluate the impact on outcome of the type of vasculitis, prognostic factors, and treatments administered at diagnosis, and to analyze treatment side effects and sequelae.

Methods

Data from PAN, MPA, and CSS patients (n = 278) who were enrolled between 1980 and 1993 were collected in 1996 and 1997 and analyzed. Two prognostic scoring systems, the Five‐Factors Score (FFS) and the Birmingham Vasculitis Activity Score (BVAS), were used to evaluate all patients at the time of diagnosis.

Results

The mean (±SD) followup of the entire population was 88.3 ± 51.9 months (range 3 days to 192 months). Of the 85 deaths recorded, at least 41 were due to progressive vasculitis or its consequences. Death rates reflected disease severity, as assessed by the FFS (P = 0.004) and the BVAS (P < 0.0002), and the 2 scores were correlated (r = 0.69). Relapses, rarer in hepatitis B virus (HBV)–related PAN (7.9%) than in MPA (34.5%) (P = 0.004), occurred in 56 patients (20.1%) and did not reflect disease severity. Survival curves were similar for the subpopulation of 215 patients with CSS, MPA, and non–HBV‐related PAN who were given first‐line corticosteroids (CS) with or without cyclophosphamide (CYC). However, CS with CYC therapy significantly prolonged survival for patients with FFS scores ≥2 (P = 0.041). Relapse rates were similar regardless of the treatment regimen; only patients treated with CS alone had uncontrolled disease. CYC was associated with a greater frequency of side effects (P < 0.00001).

Conclusion

Rates of mortality due to PAN (related or unrelated to HBV), MPA, and CSS reflected disease severity and were higher than the mortality rate in the general population (P < 0.0004). Rates of relapse, more common in MPA than HBV‐related PAN patients, did not reflect disease severity. Survival rates were better among the more severely ill patients who had received first‐line CYC. Based on these findings, we recommend that the intensity of the initial treatment be consistent with the severity of the disease. The use of the FFS and BVAS scores improved the ability to evaluate the therapeutic response.

     

Prevalences of polyarteritis nodosa,microscopic polyangiitis,Wegener's granulomatosis,and Churg‐Strauss syndrome in a French urban multiethnic population in 2000: A capture–recapture estimate

Objective

To estimate the prevalences of polyarteritis nodosa (PAN), microscopic polyangiitis (MPA), Wegener's granulomatosis (WG), and Churg‐Strauss syndrome (CSS).

Methods

Cases were collected in Seine–St. Denis County, a northeastern suburb of Paris, which has 1,093,515 adults (≥15 years), 28% of whom are of non‐European ancestry. The study period encompassed the entire calendar year 2000. Cases were identified by general practitioners, the departments of all the public hospitals and 2 large private clinics, and the National Health Insurance System. The Chapel Hill nomenclature was used to define MPA, and American College of Rheumatology criteria to define WG and CSS; PAN was diagnosed based on clinical laboratory, histological and/or angiographic findings. Three‐source capture–recapture analysis was performed to correct for incomplete case ascertainment.

Results

A total of 75 cases were retained and capture–recapture analysis estimated that 23.8 cases had been missed by any 1 of the 3 sources. Accordingly, prevalences per 1,000,000 adults (95% confidence interval [95% CI]) were estimated to be 30.7 (95% CI 21–40) for PAN, 25.1 (95% CI 16–34) for MPA, 23.7 (95% CI 16–31) for WG, and 10.7 (95% CI 5–17) for CSS. The overall prevalence was 2.0 times higher for subjects of European ancestry than for non‐Europeans (P = 0.01).

Conclusions

This study provides the first prevalence estimates for these 4 vasculitides for a multiethnic, urban population. The significantly higher prevalence observed for Europeans may infer a genetic susceptibility of Caucasians. Compared with previous estimates based mostly on rural populations, the higher frequency of PAN and the lower frequency of WG might suggest specific environmental etiologic factors.

     

Distribution of coronary atherosclerosis in patients with coronary artery disease

The distribution of coronary atherosclerosis has not been fully clarified. We measured coronary artery calcium score (CACS) in 624 consecutive patients for the right coronary artery (RCA), left main trunk (LMT), left anterior descending coronary artery (LAD), and left circumflex coronary artery (LCx), then calculated total CACS. Coronary artery calcium score was measured using the Agatston method. We divided these patients into four groups: CACS 1–100 (Group A, n = 267), CACS 101–400 (Group B, n = 160), CACS 401–1000 (Group C, n = 110), and CACS >1000 (Group D, n = 87). In Group A, B, and C, the CACS in LAD was significantly higher than in the other three arteries (P < 0.0001). In Group D, the CACS was not significantly different between LAD and RCA (P = 0.6930). In Groups A, B, and C, coronary artery calcium (CAC) was more frequently found in LAD compared with other arteries (P < 0.0001). However, in Group D the prevalence of CAC was not significantly different among the three arteries (P = 0.4435). Coronary artery calcium was found more frequently in LAD than in the other coronary arteries in patients with mild to high CAC, but not in those with very high CAC.     

Association of coronary artery calcium with severity of myocardial ischemia in left anterior descending, left circumflex, and right coronary artery territories

Background:

An increasing coronary artery calcium score is associated with a higher likelihood of myocardial ischemia.

Hypothesis:

The association of the coronary calcium score with myocardial ischemia in different coronary arteries needed to be investigated.

Methods:

We correlated the coronary artery calcium (CAC) score with the severity of myocardial ischemia diagnosed by myocardial perfusion imaging in the left anterior descending (LAD), left circumflex (LCX), and right coronary artery (RCA) territories in 206 patients, mean age 66 years, without cardiac stents or coronary artery surgery.

Results:

The mean CAC score in the LAD coronary artery was 160 ± 218 in patients with no or mild ischemia and 336 ± 379 in patients with moderate or severe ischemia (P = 0.039). The mean CAC score in the LCX coronary artery was 57 ± 117 in patients with no or mild ischemia and 161 ± 191 in patients with moderate or severe ischemia (P = 0.018). The mean CAC score in the RCA was 114 ± 237 in patients with no or mild ischemia and 261 ± 321 in patients with moderate or severe ischemia (P = 0.045). Stepwise linear regression analysis showed that male gender (P < 0.0001), age (P < 0.0001), and moderate or severe ischemia (P = 0.023) were significantly associated with high LAD coronary artery CAC scores. Male gender (P < 0.0001), age (P = 0.0002), and moderate or severe ischemia (P = 0.006) were significantly associated with high LCX coronary artery CAC scores. Male gender (P < 0.0001) and age (P < 0.0001) were significantly associated with high RCA CAC scores.

Conclusions:

Higher CAC scores are significantly associated with moderate or severe ischemia in the LAD and LCX coronary arteries. © 2011 Wiley Periodicals, Inc. The authors have no funding, financial relationships, or conflicts of interest to disclose.     

The bifurcation study using 64 multislice computed tomography

Background: Various two‐stent techniques have been applied to aggressively treat bifurcation lesions as the introduction of drug‐eluting stents (DES) and the importance of the bifurcation angle and three‐dimensional (3D) structure has come to be recognized. Recent 64 multislice computed tomography (MSCT) technology provides accurate information about the 3D bifurcation geometry of the coronary arteries and with reproducibility. Objectives: The purpose of this study is to disclose the coronary bifurcation angle and 3D structure in humans and elucidate the importance of bifurcation angle for the crush technique using MSCT. Methods: Two hundred and nine patients who were suspected to have angina pectoris and underwent CT angiography using MSCT were examined. The 3D‐volume rendering (VR) image was reconstructed by two technicians and was used for the assessment of each coronary bifurcation angles. Results: The average LMT bifurcation angles (∠LMT‐LAD, ∠LMT‐LCx, ∠LAD‐LCx) were 143 ± 13°, 121 ± 21°, and 72 ± 22°, respectively, the average ∠LAD‐D was 138 ± 19°, the average ∠LCx‐OM was 134 ± 23°, the average distal RCA bifurcation angles (∠RCA‐4AV, ∠RCA‐4PD, ∠4AV‐4PD) were 152 ± 15°, 137 ± 20°, and 61 ± 21°, respectively. In addition, a percentage of steep angled bifurcation (<110°) was significantly higher in the LMT (26%) than in other bifurcations (P < 0.05). Conclusions: LMT bifurcation has been shown to have a higher rate of steep angled bifurcation in humans, it is therefore necessary to take the bifurcation angle into consideration in the case of LMT stenting. These data suggest that a bifurcation study using MSCT can clarify the 3D structure of coronary bifurcation and may provide useful information for bifurcation stenting. © 2009 Wiley‐Liss, Inc.     

Elevated interleukin‐4 and interleukin‐13 production by T cell lines from patients with Churg‐Strauss syndrome

Objective

To investigate cytokine production patterns of T cell lines (TCL) from patients with Churg‐Strauss syndrome (CSS).

Methods

Short‐term polyclonal TCL were generated from peripheral blood of patients with CSS or Wegener's granulomatosis (WG) and healthy controls (HC). TCL were established in the presence of interleukin‐2 (IL‐2) and phytohemagglutinin and were phenotypically characterized by flow cytometry. Th1/Th2 cytokine production by stimulated TCL (72 hours) was analyzed by enzyme‐linked immunosorbent assay.

Results

TCL that represented the progeny of in vivo–activated T cells from CSS patients displayed a heterogeneous immunophenotype, with a predominance of CD4+ T cells when compared with WG TCL, which were predominantly CD8+. All CSS TCL shared the ability to produce large amounts of interferon‐γ (IFNγ), IL‐4, and IL‐13 compared with HC (P = 0.014 for all 3). Production of IL‐4 and IL‐13 was higher in CSS TCL than in WG TCL (P = 0.014 for both). IL‐5 production was up‐regulated in WG TCL compared with CSS TCL (P = 0.014). Compared with HC, WG TCL showed increased production of IFNγ (P = 0.021), IL‐5 (P = 0.043), and IL‐13 (P = 0.021).

Conclusion

Our results indicate that, while there is evidence for both a type 1 and a type 2 response in CSS, type 2 cytokine production pattern appears to predominate in this disease when compared with WG and HC.

     

Thrombolysis in myocardial infarction frame count with angiographically normal coronary arteries and its relationship to ST-segment depression

BACKGROUND: The thrombolysis in myocardial infarction frame count (TFC) has been proposed as a simple, reproducible, objective and quantitative method to assess coronary blood flow. However, the TFC in normal coronary arteries has not been investigated in detail. The aim of this study was to determine normal TFC values and investigate their correlation with ST-segment depression during exercise testing (ET). METHODS AND RESULTS: The TFC was measured in 116 cases with normal coronary arteries who underwent ET. The ST segment was evaluated on 12-lead electrocardiograms at 60 ms after the J-point. Horizontal or downsloping ST-segment depression of > or = 0.5 mm was recorded and the sum of the depressions was calculated. When ST-segment depression > or = 1 mm compared to the level of PR segment on two or more leads was detected, the test was accepted as positive. The TFC for the left anterior descending coronary artery (LAD) was significantly higher than those for the left circumflex coronary artery (LCx) and the right coronary artery (RCA). The TFC of coronary arteries was significantly higher in patients with ET positive (for LAD, 39.5 +/- 10.7 compared with 30.1 +/- 7.6 frames; for LCx, 29.2 +/- 9.3 compared with 23.6 +/- 6.5 frames; and for RCA, 30.7 +/- 11 compared with 23.7 +/- 7 frames; P < 0.001 for overall comparisons). Women had a lower TFC than men in the LAD. Moreover, it was determined that the TFC values for the LAD, LCx and RCA significantly correlated with the sum of ST-segment depression (r = 0.57, r = 0.46 and r = 0.41, respectively, P < 0.001 for overall correlations). It was also determined that the TFC was affected by the proximal diameter of the coronary arteries. CONCLUSIONS: The results of this study highlight the differences of the TFC in normal LAD, LCx and RCA. In patients with normal coronary arteries, the fact that the TFC is higher in ET-positive than in ET-negative patients may explain false positive results of ET. Sex and coronary artery diameter should be taken into consideration in evaluating the TFC.     

Frequency of abnormal fractional flow reserve measurements among major coronary arteries

Background

Fractional flow reserve(FFR) is a validated tool for evaluating functional severity and guiding the revascularization of angiographically moderate coronary artery lesions.

Evaluation of very low amplitude intra-QRS potentials during the initial minutes of acute transmural myocardial ischemia

Introduction

Low-level electrocardiographic changes from depolarization wavefront may accompany acute myocardial ischemia. The purpose of this study was to assess the changes of microvolt amplitude intra-QRS potentials induced by elective percutaneous coronary interventions (PCI).

Methods

Fifty-seven patients with balloon inflation periods ranging from 3.1 to 7.3 minutes (4.9 ± 0.7 min) were studied. Nine leads continuous high-resolution ECG before and during PCI were recorded and signal-averaged. Abnormal intra-QRS at microvolt level (μAIQP) were obtained using a signal modeling approach. μAIQP, R-wave amplitude and QRS duration were measured in the processed ECG during baseline and PCI episodes.

Results

The mean μAIQP amplitude significantly decreased for each of the standard 12 leads at the PCI event respect to baseline. Left anterior descending artery (LAD) occlusion resulted in a decrease μAIQP in both the precordial leads and the limb leads, while right coronary (RCA) and left circumflex (LCx) arteries occlusions mainly affected limb leads. R-wave amplitude increased during PCI in RCA and LCx groups in lead III but decreased in the precordial leads, while the amplitude decreased in the LAD group in lead III. The average duration of the QRS augmented in groups RCA and LCx but not in the LAD group.

Conclusions

Abnormal intra-QRS potentials at the level of μV provide an excellent tool to characterize the very-low amplitude fragmentation of the QRS complex and its changes due to ischemic injuries. μAIQP shows promise as a new ECG index to measure electrophysiologic changes associated with acute myocardial ischemia.     

Are environmental factors important in primary systemic vasculitis?: A case–control study

Objective

To investigate the association between primary systemic vasculitis (PSV) and environmental risk factors.

Methods

Seventy‐five PSV cases and 273 controls (220 nonvasculitis, 19 secondary vasculitis, and 34 asthma controls) were interviewed using a structured questionnaire. Factors investigated were social class, occupational and residential history, smoking, pets, allergies, vaccinations, medications, hepatitis, tuberculosis, and farm exposure in the year before symptom onset (index year). The Standard Occupational Classification 2000 and job‐exposure matrices were used to assess occupational silica, solvent, and metal exposure. Stepwise multiple logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (95% CI) adjusted for potential confounders. Total PSV, subgroups (47 Wegener's granulomatosis [WG], 12 microscopic polyangiitis, 16 Churg‐Strauss syndrome [CSS]), and antineutrophil cytoplasmic antibody (ANCA)–positive cases were compared with control groups.

Results

Farming in the index year was significantly associated with PSV (OR 2.3 [95% CI 1.2–4.6]), with WG (2.7 [1.2–5.8]), with MPA (6.3 [1.9–21.6]), and with perinuclear ANCA (pANCA) (4.3 [1.5–12.7]). Farming during working lifetime was associated with PSV (2.2 [1.2–3.8]) and with WG (2.7 [1.3–5.7]). Significant associations were found for high occupational silica exposure in the index year (with PSV 3.0 [1.0–8.4], with CSS 5.6 [1.3–23.5], and with ANCA 4.9 [1.3–18.6]), high occupational solvent exposure in the index year (with PSV 3.4 [0.9–12.5], with WG 4.8 [1.2–19.8], and with classic ANCA [cANCA] 3.9 [1.6–9.5]), high occupational solvent exposure during working lifetime (with PSV 2.7 [1.1–6.6], with WG 3.4 [1.3–8.9], and with cANCA 3.3 [1.0–10.8]), drug allergy (with PSV 3.6 [1.8–7.0], with WG 4.0 [1.8–8.7], and with cANCA 4.7 [1.9–11.7]), and allergy overall (with PSV 2.2 [1.2–3.9], with WG 2.7 [1.4–5.7]). No other significant associations were found.

Conclusion

A significant association between farming and PSV has been identified for the first time. Results also support previously reported associations with silica, solvents, and allergy.

     

Microscopic polyangiitis and polyarteritis nodosa: How and when do they start?

Objective

To describe initial clinical symptoms attributable to microscopic polyangiitis (MPA) or polyarteritis nodosa (PAN).

Methods

We retrospectively reviewed the medical files of 72 patients (mean followup 6.7 years) with biopsy‐proven MPA (n = 36) or PAN (n = 36).

Results

Initial manifestations were similar in both entities except for peripheral neuropathy (P = 0.02) and gastrointestinal tract involvement (P = 0.006), which were significantly more frequent in PAN, and general signs alone in MPA (8%; P = 0.02). The mean time to diagnosis was 9.8 ± 19.4 months; 35% of the patients died and 26% relapsed; significantly more MPA than PAN patients relapsed (P = 0.03). Time to diagnosis ≥90 days was associated with a trend toward more patients relapsing (P = 0.12), but not with an increased risk of mortality.

Conclusion

Initial symptoms of MPA and PAN are usually nonspecific and last for several months before the diagnosis is made. A longer time to diagnosis is associated with a tendency to a higher relapse rate.

     

Percutaneous Coronary Intervention for Chronic Total Occlusion in Single Coronary Arteries

We retrospectively compared the results of percutaneous coronary intervention (PCI) and optimal medical therapy (OMT) for chronic total occlusion (CTO) in single coronary arteries to determine whether outcomes depend on the artery involved.From January 2004 through November 2015, a total of 731 patients were treated at our center for CTO in the left anterior descending coronary artery (LAD) (234 patients, 32%), left circumflex coronary artery (LCx) (184, 25.2%), or right coronary artery (RCA) (313, 42.8%). We further classified patients by treatment (PCI or OMT) and compared the cumulative incidence of major adverse cardiac events (MACE) and the composite of total death or myocardial infarction, as well as change in left ventricular ejection fraction from baseline.The 5-year cumulative incidence of MACE was similar between the treatment groups regardless of target vessel. The 5-year cumulative incidence of the composite of total death or myocardial infarction was significantly lower after PCI than after OMT or failed PCI in the LCx (2.6% vs 11.5%; P=0.020; log-rank) and RCA (5.8% vs 17.2%; P=0.002) groups, but not in the LAD group. Cox proportional hazards regression analysis indicated that PCI independently predicted a lower incidence of the composite of total death or myocardial infarction in the LCx group (hazard ratio [HR]=0.184; 95% CI, 0.0035–0.972; P=0.046) and the RCA group (HR=0.316; 95% CI, 0.119–0.839; P=0.021).The artery involved does not appear to affect clinical outcomes of successful PCI for single-vessel CTO. Further investigation in a randomized clinical trial is warranted.     

Treatment of polyarteritis nodosa and microscopic polyangiitis with poor prognosis factors: A prospective trial comparing glucocorticoids and six or twelve cyclophosphamide pulses in sixty‐five patients

Objective

Because the optimal cyclophosphamide (CY) treatment duration for severe polyarteritis nodosa (PAN) without virus infection and microscopic polyangiitis (MPA) has not been established, we conducted a trial to compare the effectiveness of 6 versus 12 CY pulses given in combination with corticosteroids (CS).

Methods

Sixty‐five (18 PAN, 47 MPA) previously untreated patients were randomized to receive 12 (n = 34) or 6 (n = 31) CY pulses combined with CS. PAN and MPA were histologically proven or met ACR criteria. All patients presented ≥1 factor of severity according to the five factor score (FFS). CY pulses were administered every 2 weeks for 1 month, then every 4 weeks. The end point of the study was the number of events (relapses and/or deaths) occurring in each group, analyzed according to an intention‐to‐treat strategy. The outcome was evaluated by Cox proportional hazards analysis.

Results

The baseline characteristics were similar for both groups. The mean (± SD) followup was 32 ± 21 months. Survival analysis showed a significantly lower relapse probability (P = 0.02; hazards ratio [HR] = 0.34) and higher event‐free survival (P = 0.02, HR = 0.44) for the 12 CY‐pulse group while the mortality rates were not significantly different (P = 0.47).

Conclusion

These results suggest that 6 CY pulses are less effective than 12 CY pulses to treat severe PAN and MPA, particularly with respect to the risk of relapses.

     

The primary anomalies of coronary artery origin and course: A coronary angiographic analysis of 16,573 patients

BACKGROUND/OBJECTIVES:

Coronary artery anomalies are present at birth, but relatively few are symptomatic. The majority are discovered incidentally. In the present study, coronary angiograms performed in the authors’ centre (Ondokuz Mayis University Hospital, Samsun, Turkey) were analyzed to determine the prevalence and types of coronary artery origin and course anomalies.

METHODS:

Coronary angiographic data of 16,573 patients were analyzed. Anomalous origins and courses of coronary arteries were assessed.

RESULTS:

Anomalous coronary arteries were detected in 48 (0.29%) of 16,573 patients. The origin of the circumflex (Cx) artery from the right coronary artery (RCA) or right sinus of Valsalva was the most common anomaly (28 patients [58.3%]). An anomalous RCA originating from the left anterior descending artery (LAD) or Cx artery was observed in six patients (12.5%). The left coronary artery originated from the right sinus of Valsalva in five patients, and the LAD originated from the RCA or the right sinus of Valsalva in five patients. The RCA originated from the left sinus of Valsalva in three patients and from an ectopic ostium in the ascending aorta in one patient.

CONCLUSIONS:

The most frequent anomaly observed in the present study was related to the Cx artery, which is consistent with previous reports. Although coronary artery anomalies are rare, they may cause difficulties during coronary interventions or cardiac surgery and may occasionally result in sudden cardiac death. Therefore, the recognition and diagnosis of these anomalies is important and requires specialization in coronary angiographic techniques and other imaging modalities.     

Regional coronary flow and contractile reserve in patients with idiopathic dilated cardiomyopathy

OBJECTIVES: The purpose of this study was to assess regional coronary flow and contractile reserve in patients with idiopathic dilated cardiomyopathy (IDCM). BACKGROUND: Although IDCM has been associated with alterations in coronary blood flow and contractile reserve, little is known about their regional distribution and correlation. METHODS: Fourteen patients with IDCM and 11 control subjects underwent coronary flow velocity (APV) measurements in the left anterior descending (LAD), left circumflex (LCx), and right coronary (RCA) arteries at baseline (b) and at maximal hyperemia (h). Coronary flow reserve (CFR) was defined as h-APV/b-APV. Wall thickening was assessed in 16 segments (7 assigned to LAD, 5 to LCx, and 4 to RCA) both at rest and under peak stress during low-dose dobutamine echocardiography. Regional contractile reserve was defined as the percentage difference in wall motion score index between rest and stress in each vascular territory. RESULTS: Although there were no significant differences in b-APV, patients with IDCM had significantly lower h-APV than controls in all three vascular territories and reduced CFR (LAD: 2.79 +/- 0.43 vs. 3.48 +/- 0.51, p < 0.05; LCx: 2.71 +/- 0.39 vs. 3.36 +/- 0.65, p < 0.05; and RCA: 3.43 +/- 0.55 vs. 4.02 +/- 0.73, p < 0.05). There was also a significant correlation between CFR and the corresponding contractile reserve in the vascular territory of the LAD (r = 0.75, p = 0.002) and the LCx (r = 0.64, p = 0.014). CONCLUSIONS: Patients with IDCM have alterations in regional coronary flow and reduced CFR. Furthermore, the correlation between regional CFR and the corresponding contractile reserve indicates that microvascular dysfunction may have a pathophysiologic role in the evolution of the disease.     

Slow Coronary Flow: Correlations with Myocardial Perfusion Tomography and Coronary Arteriography

A reduction in velocity in coronary artery contrast filling during coronary arteriography that is called slow coronary flow is one of the reasons of myocardial ischemia. Ischemia mechanism hasn't been understood. We evaluated coronary arteriographic and scintigraphic properties in patients with a slow flow pattern (SFP). The study included 60 patients who revealed SFP in their coronary arteriograms. The control group consisted of 50 patients with normal myocardial perfusion and normal coronary arteries in their coronary arteriograms. The Thrombolysis in Myocardial Infarction (TIMI) flow count method was used for the assessment of slow coronary flow. Single day rest-stress Technetium-99m hexakis-2-methoxy-isobutyl isonitrile (Tc-99m MIBI) myocardial perfusion tomography was performed to all study patients. Patients with SFP revealed both higher frame counts in native coronary arteries and higher average frame counts. In control patients, the average frame count was 26.4 ± 3.5 (LAD: 35.4 ± 3.3, LCx: 22.5 ± 4.5, RCA: 21.5 ± 2.8). In patients with SFP the average frame count was 64.40 ± 16.64 (LAD: 85.75 ± 24.39, LCx: 57.21 ± 15.25, RCA: 53 75 ± 17.81) (p < 0.001). Myocardial perfusion tomography showed ischemia in 17 patients (Group 1), while 43 patients in Group 2 revealed no perfusion defect. There were no statistically significant differences between Groups 1 and 2 in frame counts. In conclusion, no correlation was observed between the time needed to fill a native coronary artery and ischemia even if there is SFP.     

The Five-Factor Score revisited: assessment of prognoses of systemic necrotizing vasculitides based on the French Vasculitis Study Group (FVSG) cohort

The 1996 Five-Factor Score (FFS) for systemic necrotizing vasculitides (polyarteritis nodosa [PAN], microscopic polyangiitis [MPA], and Churg-Strauss syndrome [CSS]) is used to evaluate prognosis at diagnosis. In the current study we revisited the FFS, this time including Wegener granulomatosis (WG).We analyzed clinical, laboratory, and immunologic manifestations present at diagnosis of systemic necrotizing vasculitides for 1108 consecutive patients registered in the French Vasculitis Study Group database. All patients met the American College of Rheumatology and Chapel Hill nomenclature criteria. Univariable and multivariable analyses yielded the 2009 FFS for the 4 systemic necrotizing vasculitides.Overall mortality was 19.8% (219/1108); mortality for each of the SNV is listed in descending order: MPA (60/218, 27.5%), PAN (86/349, 24.6%), CSS (32/230, 13.9%), and WG (41/311, 13.2%) (p < 0.001). The following factors were significantly associated with higher 5-year mortality: age >65 years, cardiac symptoms, gastrointestinal involvement, and renal insufficiency (stabilized peak creatinine ≥150 μmol/L). All were disease-specific (p < 0.001); the presence of each was accorded +1 point. Ear, nose, and throat (ENT) symptoms, affecting patients with WG and CSS, were associated with a lower relative risk of death, and their absence was scored +1 point (p < 0.001). Only renal insufficiency was retained (not proteinuria or microscopic hematuria) as impinging on outcome. According to the 2009 FFS, 5-year mortality rates for scores of 0, 1, and ≥2 were 9%, 21% (p < 0.005), and 40% (p < 0.0001), respectively.The revised FFS for the 4 systemic necrotizing vasculitides now comprises 4 factors associated with poorer prognosis and 1 with better outcome. The retained items demonstrate that visceral involvement weighs heavily on outcome. The better WG prognosis for patients with ENT manifestations, even for patients with other visceral involvement, compared with the prognosis for those without ENT manifestations, probably reflects WG phenotype heterogeneity.     

AC13, a C‐terminal fragment of apolipoprotein A‐I,is a candidate biomarker for microscopic polyangiitis

Objective

Microscopic polyangiitis (MPA) is necrotizing vasculitis of unknown etiology. We analyzed the serum peptide profile of MPA to find a biomarker for this disease.

Methods

Serum peptides from 33 patients with MPA, 7 with granulomatosis with polyangiitis (Wegener's), 7 with Churg‐Strauss syndrome, 6 with giant cell arteritis, and 25 with systemic lupus erythematosus (SLE) were comprehensively analyzed by mass spectrometry. Peptide function on human microvascular endothelial cells (HMVECs) was examined by enzyme‐linked immunosorbent assay and real‐time polymerase chain reaction.

Results

A total of 102 serum peptides were detected from the 78 patients. One of the peptides, peptide 1,523, showed significantly higher ion intensity in MPA (mean ± SD 46.8 ± 39.3 arbitrary units [AU]) than in the other systemic vasculitides (14.1 ± 12.2 AU) (P < 0.05) or in SLE (17.0 ± 12.1 AU) (P < 0.05). In MPA, peptide 1,523 showed significantly higher ion intensity before treatment than 1 week (P < 0.05) and 6 weeks (P < 0.05) after the initiation of treatment. Peptide 1,523 was identified as 13 C‐terminal amino acid residues of apolipoprotein A‐I (Apo A‐I) and was designated “AC13.” Validation of AC13 ion intensity using another MPA cohort (n = 14) similarly showed significantly higher ion intensity (90.1 ± 167.9 AU) compared to 14 patients with rheumatoid arthritis (8.6 ± 5.4 AU) (P < 0.01) and 14 healthy subjects (11.8 ± 6.1 AU) (P < 0.01). Serum concentrations of Apo A‐I and high‐density lipoprotein cholesterol were down‐regulated in MPA before treatment and returned to their normal ranges 6 weeks after the initiation of treatment (both P < 0.01). Stimulation of HMVECs with AC13 significantly up‐regulated secretion of interleukin‐6 (IL‐6) (P < 0.05) and IL‐8 (P < 0.01).

Conclusion

AC13, a candidate biomarker for MPA, may be useful for monitoring disease activity and may exacerbate vascular inflammation through up‐regulation of proinflammatory cytokines.