Total management of chronic obstructive pulmonary disease (COPD) as an independent risk factor for cardiovascular disease.

Patients with cardiovascular disease (CVD) often have multiple comorbid conditions that may interact with each other, confound the choice of treatments, and reduce mortality. Chronic obstructive pulmonary disease (COPD) is one of the most important comorbidities of CVD, which causes serious consequences in patients with ischemic heart disease, stroke, arrhythmia, and heart failure. COPD shares common risk factors such as tobacco smoking and aging with CVD, is associated with less physical activity, and produces systemic inflammation and oxidative stress. Overall, patients with COPD have a 2-3-fold increased risk of CVD as compared to age-matched controls when adjusted for tobacco smoking. Chronic heart failure (HF) is a frequent and important comorbidity which has a significant impact on prognosis in COPD, and vice versa. HF overlaps in symptoms and signs and has a common comorbidity with COPD, so that diagnosis of COPD is difficult in patients with HF. The combination of HF and COPD presents many therapeutic challenges including beta-blockers (BBs) and beta-agonists. Inhaled long-acting bronchodilators including beta2-agonists and anticholinergics for COPD would not worsen HF. Diuretics are relatively safe, and angiotensin-converting enzyme inhibitors are preferred to treat HF accompanied with COPD. BBs are only relatively contraindicated in asthma, but not in COPD. Low doses of cardioselective BBs should be aggressively initiated in clinically stable patients with HF accompanied with COPD combined with close monitoring for signs of airway obstruction and gradually up-titrated to the maximum tolerated dose. Encouraging appropriate and aggressive treatment for both HF and COPD should be recommended to improve quality of life and mortality in HF patients with COPD.

The relationship between the COPD Assessment Test score and airflow limitation in Japan in patients aged over 40 years with a smoking history.

BACKGROUND: A large number of chronic obstructive pulmonary disease (COPD) patients in Japan remain undiagnosed, primarily due to the underuse of spirometry. Two studies were conducted to see whether the COPD Assessment Test (CAT) in primary care has the potential to identify those patients who need spirometry for a diagnosis of COPD and to determine whether patients with cardiovascular disease had airflow limitation, which could be detected by CAT. MATERIALS AND METHODS: Two multicenter, noninterventional, prospective studies (studies 1 and 2) were conducted across Japan. Patients in both studies were ≥40 years old with a smoking history. Those in study 1 were seen in primary care and had experienced repeated respiratory tract infections, but had no diagnosis of COPD. Patients in study 2 were identified in cardiovascular disease clinics when routinely visiting for their cardiovascular disease. All patients completed the CAT prior to lung-function testing by hand-held spirometry. The presence of airflow limitation was defined as a forced expiratory volume in 1 second (FEV1)/FEV6 ratio<0.73. RESULTS: A total of 3,062 subjects completed the CAT (2,067 in study 1, 995 in study 2); 88.8% were male, and the mean age (±standard deviation) was 61.5±11.6 years. Airflow limitation was found in 400 (19.4%) patients in study 1, and 269 (27.0%) in study 2. The CAT score in patients with airflow limitation was significantly higher than in patients without airflow limitation in both studies: 8.6 (95% confidence interval [CI] 7.9-9.2) versus 7.4 (95% CI 7.1-7.6) in study 1, and 8.3 (95% CI 7.5-9.2) versus 6.4 (95% CI 6.0-6.8) in study 2 (both P<0.001). CONCLUSION: These findings suggest that the CAT has the potential to identify patients with cardiovascular disease or a history of frequent chest infections who need spirometry to diagnose COPD.

Prevalence of airflow limitation in outpatients with cardiovascular diseases in Japan.

BACKGROUND AND OBJECTIVES: Cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD) commonly coexist and share common risk factors. The prevalence of COPD in outpatients with a smoking history and CVD in Japan is unknown. The aim of this study was to determine the proportion of Japanese patients with a smoking history being treated for CVD who have concurrent airflow limitation compatible with COPD. A secondary objective was to test whether the usage of lung function tests performed in the clinic influenced the diagnosis rate of COPD in the patients identified with airflow limitation. METHODS: In a multicenter observational prospective study conducted at 17 centers across Japan, the prevalence of airflow limitation compatible with COPD (defined as forced expiratory volume (FEV)1/FEV6 <0.73, by handheld spirometry) was investigated in cardiac outpatients ≥40 years old with a smoking history who routinely visited the clinic for their CVD. Each patient completed the COPD Assessment Test prior to spirometry testing. RESULTS: Data were available for 995 patients with a mean age of 66.6±10.0 years, of whom 95.5% were male. The prevalence of airflow limitation compatible with COPD was 27.0% (n=269), and 87.7% of those patients (n=236) did not have a prior diagnosis of COPD. The prevalence of previously diagnosed airflow limitation was higher in sites with higher usage of lung function testing (14.0%, 15.2% respectively) compared against sites where it is performed seldom (11.1%), but was still low. CONCLUSION: The prevalence of airflow limitation in this study indicates that a quarter of outpatients with CVD have COPD, almost all of whom are undiagnosed. This suggests that it is important to look routinely for COPD in CVD outpatients.

Detection of coronary artery disease using coronary flow velocity reserve by transthoracic Doppler echocardiography versus multidetector computed tomography coronary angiography: influence of calcium score.

BACKGROUND: There have been no clinical data specifying the degree of calcium deposition at which coronary flow velocity reserve (CFVR) measurement using transthoracic Doppler echocardiography surpasses 320-row multidetector computed tomographic coronary angiography (CTCA) in detecting obstructive coronary artery disease. METHODS: One hundred seventy patients who underwent invasive coronary angiography, transthoracic Doppler echocardiography, and CTCA were prospectively enrolled. Coronary artery stenosis was defined as percentage diameter stenosis ≥ 50% on invasive coronary angiography. CFVR < 2.0 and narrowing ≥ 50% measured with CTCA were the thresholds indicating the presence of coronary artery stenosis. The degree of coronary artery calcification was also assessed using the Agatston calcium score method by computed tomography. RESULTS: The majority of patients (89%) were classified as having either high or intermediate pretest probability of coronary artery disease. Significant coronary artery stenoses by invasive coronary angiography were found in 71 patients and 104 vessels. Although the overall diagnostic performance of CTCA was comparable with that of CFVR measurement for detecting coronary artery stenosis, only the diagnostic performance of CTCA was negatively affected by the extent of a patient's coronary artery calcification. Receiver operating characteristic curve analysis indicated that only CFVR measurement is diagnostically accurate when calcium scores are >319 in the patient-based assessment, 189 for the left anterior descending coronary artery, 98 for the left circumflex coronary artery and 282 for the right coronary artery. CONCLUSIONS: Transthoracic Doppler echocardiography and 320-row multidetector CTCA successfully diagnosed significant coronary artery stenosis with high feasibility and accuracy. However, only the diagnostic performance of CTCA was negatively affected by the extent of a patient's coronary artery calcification, and therefore the diagnostic performance of CFVR measurement for detecting coronary artery stenosis surpassed that of CTCA when the calcium score exceeded specified cutoff values.

Myocardial perfusion reserve is impaired in patients with chronic obstructive pulmonary disease: a comparison to current smokers.

AIMS: Recent studies have demonstrated that chronic obstructive pulmonary disease (COPD) is associated with cardiovascular disease (CVD). However, the association between COPD and coronary microcirculatory dysfunction is unknown. We sought to assess whether myocardial perfusion reserve (MPR) is impaired in patients with COPD, even in the absence of regional myocardial ischaemia or infarction, by using quantitative myocardial perfusion cardiovascular magnetic resonance (CMR). METHODS AND RESULTS: We recruited 60 subjects with a normal CMR study: 20 individuals with mild-to-moderate COPD; 20 age-matched control smokers, and 20 age-matched control-never smokers. Individuals with established CVD and diabetes mellitus were excluded. Stress-rest myocardial blood flow (MBF) was quantified in 16 myocardial segments by using a Patlak plot method. There were no significant differences in the rest MBF among COPD patients, control smokers, and control-never smokers. However, the mean MPR was significantly lower in COPD patients than in control smokers and control-never smokers (1.76 ± 0.58, 2.57 ± 1.30, and 3.56 ± 1.27, respectively). Univariate associations with MPR were smoking (r = -0.44, P < 0.001), forced expiratory volume in 1 s (FEV1) (r = 0.30, P = 0.02), haematocrit (r = 0.25, P = 0.04), and C-reactive protein (CRP; r = -0.46, P < 0.001). On multivariable analysis, the levels of CRP, FEV1, and renal dysfunction were independent predictors of the impaired MPR. The presence of COPD was associated with a five-fold increased risk of MPR <1.5 (95% confidence interval, 1.4-19.0; P = 0.01). CONCLUSIONS: The MPR, which was independently associated with systemic inflammation and airflow limitation, was impaired in patients with COPD. The presence of COPD was a powerful predictor of impaired MPR in patients without regional myocardial ischaemia or infarction.

Hypertension impairs myocardial blood perfusion reserve in subjects without regional myocardial ischemia.

Quantitative analysis of myocardial perfusion MRI can provide noninvasive assessments of myocardial perfusion reserve (MPR), which is associated with endothelial function. Endothelial function is influenced by various factors, including hypertension, diabetes, dyslipidemia, renal dysfunction and anemia. The purpose of this study was to evaluate which risk factor is the strongest effector of MPR in subjects without regional myocardial ischemia. We studied 110 patients (66 years ±10, male 68%, hypertension 76%, diabetes mellitus (DM) 40% and dyslipidemia 65%) without regional myocardial ischemia. Adenosine triphosphate (ATP) stress and rest first-pass perfusion magnetic resonance (MR) images were acquired with a 1.5-T MR system, and MPR was calculated as the ratio of stress to rest myocardial blood flow (MBF). Average rest MBF in 110 patients was 1.07±0.62 ml min⁻¹ g⁻¹, whereas stress MBF was 3.15±1.93 ml min⁻¹ g⁻¹ and the MPR was 3.33±1.82. Rest MBF correlated significantly with hematocrit, whereas stress MBF showed a strong correlation with estimated glomerular filtration rate (e-GFR). MPR was associated with hypertension, age, e-GFR, hematocrit and left ventricular mass index (LVMI). In multiple regression analysis, hypertension (P=0.003, ß=-0.274) showed the strongest correlation with MPR among other risk factors, such as diabetes (P=ns), dyslipidemia (P=ns), e-GFR (P=ns), LVMI (P=0.007, ß=-0.248) and hematocrit (P=ns) after adjusting age and gender. Hypertension is the most important effector of MPR in subjects without myocardial ischemia.

Regional myocardial perfusion reserve determined using myocardial perfusion magnetic resonance imaging showed a direct correlation with coronary flow velocity reserve by Doppler flow wire.

AIMS: Quantitative analysis of rest-stress myocardial perfusion magnetic resonance imaging (MRI) can provide assessments of regional myocardial perfusion reserve (MPR). The purpose of this study was to compare regional MPR determined by myocardial perfusion MRI with coronary flow reserve (CFR) by intracoronary Doppler flow wire. METHODS AND RESULTS: Twenty patients with suspected coronary artery disease (CAD) were studied. Average peak velocity was measured by Doppler flow wire in the resting state and during adenosine triphosphate (ATP) stress in 36 coronary arteries. CFR measurements for each patient were performed in the culprit and one non-culprit non-stenotic artery. First-pass, contrast-enhanced myocardial perfusion MR images were obtained in the resting state and during ATP stress within the week before the Doppler wire procedure. Regional myocardial blood flow (MBF) was quantified in 16 myocardial segments by analysing arterial input and myocardial output using a Patlak plot method. MPR was calculated as stress MBF divided by rest MBF. CFR measured by Doppler flow wire was compared with MPR in the myocardial segments corresponding to vessel territories. The average MPR measured by perfusion MRI was 1.77 +/- 0.62 for the culprit arteries and 3.45 +/- 0.78 for the non-culprit arteries, respectively (P < 0.001). The averaged CFR by Doppler flow wire was 1.72 +/- 0.44 in the culprit arteries and 3.14 +/- 0.74 in the non-culprit arteries, respectively (P < 0.001). For both culprit and non-culprit vessel groups, significant direct correlations were observed between MR assessments of MPR and Doppler assessments of CFR (culprit artery: R = 0.87, Non-culprit artery: R = 0.86) On Bland-Altman analysis, the mean differences between MPR determined by myocardial perfusion MRI and CFR measured by Doppler wire were 0.05 in culprit arteries (95% limit of agreement; -0.65 to 0.56) and 0.36 in non-culprit arteries (95% limit of agreement; -1.24 to 0.44). The sensitivity and specificity of MR measurement of MPR for predicting physiologically significant reduction of Doppler CFR (<2) was 88% (95% CI 61.7-98.5) and 90% (95% CI 68.3-98.8), respectively. CONCLUSION: The current results using Doppler flow wire as a reference method demonstrated that quantitative analysis of stress-rest myocardial perfusion MRI can provide a non-invasive assessment of reduced MPR in patients with CAD.

Eplerenone attenuates myocardial fibrosis in the angiotensin II-induced hypertensive mouse: involvement of tenascin-C induced by aldosterone-mediated inflammation.

Tenascin-C is an extracellular matrix glycoprotein that is supposed to be a profibrotic molecule in various fibrogenic processes. To elucidate its significance for myocardial fibrosis in the hypertensive heart, we used a mouse model with infusion of angiotensin II and examined results by histology, immunohistochemistry, in situ hybridization, and quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR). Angiotensin II treatment elevated blood pressure and expression of tenascin-C by interstitial fibroblasts in perivascular fibrotic lesions, and angiotensin II infusion caused accumulation of macrophages. It also upregulated expression of collagen Ialpha2; IIIalpha1; and proinflammatory/profibrotic mediators including transforming growth factor beta (TGFbeta), platelet-derived growth factor alpha (PDGF-A), PDGF-B, and PDGF-receptor alpha, but not IL-1beta and PDGF-receptor beta, in the myocardium. Treatment with an aldosterone receptor antagonist, eplerenone, significantly attenuated angiotensin II-induced fibrosis, expression of tenascin-C, and inflammatory changes without affecting the blood pressure level. In vitro, neither eplerenone nor aldosterone exerted any influence on tenascin-C expression of cardiac fibroblasts, whereas angiotensin II, TGF-beta1, and PDGF significantly upregulated expression of tenascin-C. These results suggest that, in the angiotensin II-induced hypertensive mouse heart: (1) tenascin-C may be involved in the progression of cardiac fibrosis and (2) aldosterone may elicit inflammatory reactions in myocardium, which might, in turn, induce tenascin-C synthesis of fibroblasts through at least 2 pathways mediated by TGF-beta and PDGF-A-B/PDGF-receptor alpha.

Antique SVG with two humps: a case of two giant aneurysms of single saphenous vein bypass graft.

Saphenous vein graft aneurysms are a rare complication of coronary artery bypass surgery. In this article, we present a 3-dimensional computed tomography image of two giant aneurysms of a single saphenous vein bypass graft.

Elevated plasma levels of fibrin degradation products by granulocyte-derived elastase in patients with disseminated intravascular coagulation.

Plasma levels of granulocyte-derived elastase (GE-XDP), D-dimer, and soluble fibrin (SF) were examined in 177 patients with disseminated intravascular coagulation (DIC) of various etiologies. Plasma levels of GE-XDP and D-dimer, but not SF, were significantly high in patients with sepsis and solid cancer. The ratio of GE-XDP/ D-dimer was significantly high in patients with trauma, burn, and sepsis, suggesting that fibrinolysis due to GE-XDP may be dominant in DIC. Plasma levels of GE-XDP and D-dimer, but not SF, were significantly high in patients with overt DIC and correlated with DIC score. Plasma levels of GE-XDP, but not SF, correlated significantly with D-dimer. Plasma levels of D-dimer, but not SF, correlated significantly with plasmin plasmin inhibitor complex (PPIC). Plasma levels of GE-XDP and D-dimer, but not SF, were significantly high in nonsurvivors. Plasma levels of GE-XDP, but not SF, correlated significantly with sepsis-related organ failure assessment (SOFA) score. These results suggest that GE-XDP is a potentially useful marker for the diagnosis of overt-DIC and as a predictor of organ failure-related outcome.

Bilateral giant coronary aneurysms diagnosed non-invasively by dynamic magnetic resonance imaging.

Giant coronary aneurysms are sometimes misdiagnosed as cardiac tumors when they are filled with thrombus. In this case, dynamic magnetic resonance imaging revealed the coronary artery and cardiac mass, and was the most useful tool for diagnosis of giant coronary aneurysms non-invasively.

A case of inverted left atrial appendage mimicking a tumor.

We report a rare case of an inverted left atrial appendage without prior cardiac surgery. A left atrial mass was incidentally found during routine echocardiography in a 19-year-old man with mitral valve prolapse. Echocardiography revealed a hyperechoic mass in the left atrium, and a neoplastic lesion could not be excluded. On magnetic resonance imaging (MRI), this mass consisted of fat tissue that showed continuation to epicardial fat, indicating an inverted left atrial appendage mimicking a tumor in the left atrium. When a mass in the left atrium is observed on echocardiography, there are several differential diagnoses, including thrombus, vegetation, and intra-atrial neoplasms such as myxomas. Recently, several studies reported cases with inverted left atrial appendages mimicking tumors in patients after cardiac operations. We present a case of inverted left atrial appendage without any prior cardiac surgery. Cardiac MRI was highly useful to obtain the final diagnosis of inverted left atrial appendage.

Plasma levels of heparin cofactor II (HCII) and thrombin-HCII complex in patients with disseminated intravascular coagulation.

Plasma levels of heparin cofactor II (HCII), thrombin-HCII complex (THC), antithrombin (AT), and thrombin-AT complex (TAT) were evaluated in patients with disseminated intravascular coagulation (DIC) associated with several underlying diseases. Plasma levels of AT were significantly reduced in almost all underlying diseases associated with DIC, but the plasma levels of HCII and HCII/AT ratio were significantly reduced only in patients with infections. While the plasma level of TAT was significantly increased in patients with all underlying diseases associated with DIC, the increase of THC was not significant. Plasma levels of AT were significantly reduced in DIC and pre-DIC associated with almost all underlying diseases, but those of HCII were significantly reduced only in DIC and pre-DIC patients with inflammatory diseases. The plasma levels of TAT were significantly increased in DIC, pre-DIC, and non-DIC patients with all underlying diseases, and those of THC were significantly increased in DIC and pre-DIC patients with inflammatory diseases. The plasma levels of THC were not significantly increased in non-DIC patients of any disease group. The decrease of AT may be caused by thrombin generation or inflammatory reaction that occurs in DIC associated with underlying diseases, while the decrease of HCII might be caused by both thrombin generation and inflammatory reaction. Finally, AT inhibits thrombin more strongly than HCII in several underlying diseases associated with DIC except for inflammatory diseases. In inflammatory diseases, HCII might play an important role in preventing the onset of DIC.