Possible role of adrenomedullin in the regulation of Fontan circulation: mature form of plasma adrenomedullin is extracted in the lung in patients with Fontan procedure

OBJECTIVE: We investigated the pathophysiological significance of molecular forms of adrenomedullin (AM) in patients after the Fontan procedure. METHODS: Plasma concentrations of mature AM (AM-m), an active form, glycine-extended AM (AM-Gly), an inactive form, and total AM (AM-T: AM-m+AM-Gly) were measured by specific immunoradiometric assay in the femoral vein, pulmonary artery and femoral artery of 29 consecutive patients after the Fontan procedure. The eleven patients who had history of Kawasaki disease and have normal coronary and hemodynamics served as control. RESULTS: Patients who underwent Fontan procedure had significantly higher venous concentrations of AM-T, AM-Gly, and AM-m than age-matched normal controls (AM-T, 12.0+/-3.3 vs. 9.6+/-2.0; AM-Gly, 10.4+/-3.0 vs. 8.5+/-1.6; AM-m, 1.6+/-0.7 vs. 1.0+/-0.6 pmol/l, each p<0.05). In patients with Fontan procedure, there were no differences in plasma AM-T, AM-Gly or AM-m levels between the femoral vein and pulmonary artery, however, there was a significant step-down in the AM-m levels, but not in plasma AM-T or AM-Gly levels, between the pulmonary artery and femoral artery (1.3+/-0.6 to 1.0+/-0.6, p<0.05). The venous concentrations of AM-m correlated negatively with systemic blood flow (cardiac output) (r=-0.46, p<0.05). CONCLUSIONS: Results suggest that in Fontan circulation plasma AM-m is increased in parallel with those of AM-T and AM-Gly and that AM-m is extracted in the lung. Extracted AM-m may be involved in the regulation of pulmonary arterial tonus, although further studies are necessary to elucidate the exact role of AM in Fontan circulation.     

Two molecular forms of plasma adrenomedullin during tilt test in healthy subjects.

There is accumulating evidence suggesting that adrenomedullin (AM) may participate in the regulation of circulatory homeostasis and pathophysiology of cardiovascular disease. A recent study revealed that two molecular forms of AM, an active form of mature AM (AM-m) and an intermediate inactive form of glycine-extended AM (AM-Gly), circulate in human plasma. The object of the present study was to evaluate the effect of orthostasis on a time course of two molecular forms of plasma AM and to compare them with the behavior of other vasoactive hormones. Twelve healthy male volunteers were studied. The experimental protocol consisted of 20 min of supine rest, tilting at 70 degrees for 20 min, and then 20 min of supine rest. Blood pressure and heart rate were measured every minute. Blood samples were obtained before, at 2 and 18 min during the tilt test, and 2 and 18 min after the test for the measurements of vasoacting hormones and hematocrit. Blood pressure and heart rate were slightly increased earlier during tilting and then remained elevated until the end of the test. The increase in heart rate and blood pressure returned to normal levels early after the tilt test. Plasma epinephrine and norepinephrine significantly increased during the tilt test. These hormones returned to normal levels 18 min after the test. The plasma renin activity, antidiuretic hormone and dopamine were also increased by the end of the tilt test, whereas plasma atrial natriuretic peptide was significantly decreased after the tilt test. Hematocrit increased slightly in the early phase of the tilt test and was further increased by the end of the test. In contrast, plasma AM-Gly or AM-m did not change during the tilt test or the recovery period. Nitric oxide metabolites did not change, either. There were no significant relationships between plasma catecholamines and AM. Plasma brain natriuretic peptide did not change during the tilt test or the recovery period, either. These results suggest that the two molecular forms of AM, AM-m and AM-Gly in plasma, did not respond to the short term tilting stress. These findings may support the hypothesis that plasma AM is secreted in a constitutive manner from the vascular wall.     

Plasma profiles of circulating granulocyte-macrophage colony-stimulating factor and soluble cellular adhesion molecules in acute myocardial infarction. Contribution to post-infarction left ventricular dysfunction

No in vivo data exist about the relationship of circulating granulocyte-macrophage colony stimulating factor (GM-CSF) and soluble adhesion molecules ICAM-1 and VCAM-1 (sICAM-1 and sVCAM-1) to the severity of acute myocardial infarction (AMI) and the pathophysiological events of post-infarction left ventricular dysfunction. We investigated the kinetics of these inflammatory mediators in the plasma of patients with AMI, and correlated the findings with the clinical severity of the disease during the first week of hospitalization as well as the degree of left ventricular dysfunction one month after the AMI. Plasma levels of inflammatory markers were determined in 41 AMI patients (all received thrombolytic treatment) by ELISA assays, serially during the first week of hospitalization and one month after hospital admission. Patients (n = 20) with uncomplicated AMI (Killip class I) were classified as group A, patients (n = 21) with AMI complicated by heart failure manifestations (Killip classes II and III) were classified as group B, while 20 age- and sex-matched volunteers were used as healthy controls. A sustained increase in GM-CSF, sICAM-1 and sVCAM-1 plasma concentrations was observed only in group B during the first week of the study. Patients from group B exhibited significantly higher levels of GM-CSF (P < 0.01), sICAM-1 (P < 0.05) and sVCAM-1 (P < 0.01) than patients from group A and the healthy controls (P < 0.001). In group B patients, significant correlations were observed between the peak of GM-CSF levels and the peak of serum creatine kinase-MB (r = 0.42; P < 0.05), white blood cell counts (r = 0.67; P < 0.001) and LVEF (r =- 0.51; P < 0.01). At one month follow-up, patients (n = 17) with severe post-infarction left ventricular dysfunction (LVEF 35%). Significant correlations were observed between GM-CSF levels and left ventricular end-diastolic volume index (r = 0.55; P < 0.001) or left ventricular end-systolic volume index (r = 0.49; P = 0.001). We have found a significant elevation of plasma GM-CSF and soluble adhesion molecules during the course of AMI, with the highest values in patients with AMI complicated by heart failure manifestations and severe left ventricular dysfunction. These monocyte-related inflammatory mediators may actively contribute to the pathophysiology of the disease and post-infarction cardiac dysfunction.     

急性心肌梗塞静脉溶栓后冠脉再通对左心室功能的影响

为进一步探讨静脉溶栓后冠脉再通对左室功能的有益影响,回顾性分析了88例静脉溶栓急性心肌梗塞(AMI)病人的二维超声心动图和部分病人的冠脉造影资料。根据溶栓再通标准分为再通组和未通组。在AMI发病后平均24.8±11.6天和22.9±24.4天分别进行了心超和冠造检查,观察室壁运动情况并测量左室射血分数(LVEF)。结果显示:未通组LVEF明显低于再通组,而室壁运动异常积分却显著高于再通组。左室扩大和室壁瘤的发生上,两组未发现有统计学差异。以上结果提示:AMI静脉溶栓使冠脉再通对左室功能和室壁运动障碍的改善起到有益的作用。     

Plasma endothelin-1 concentrations in the coronary sinus in dogs with artificially induced myocardial infarction.

We have previously reported the marked increase in plasma levels of endothelin-1 in patients with acute myocardial infarction (AMI). To investigate the effects of severe myocardial ischemia on the production of endothelin-1, plasma concentrations of endothelin-1 were measured by a sandwich-type enzyme immunoassay that we developed recently in both the coronary sinus and the aorta of dogs with artificially induced AMI. Dogs were anesthetized and chests were opened. The proximal left anterior descending coronary artery was completely occluded by ligation for 1 h and then was reperfused for 1 h. Throughout the experiment (at the end of occlusion for 1 h, at the beginning of reperfusion, at the end of reperfusion for 1 h), plasma endothelin-1 levels were not significantly altered either in the coronary sinus or in the aorta. The present findings indicate that severe myocardial ischemia itself does not affect the production of endothelin-1 in the coronary circulation of dogs.     

Na(+)/H(+) exchange subtype 1 inhibition reduces endothelial dysfunction in vessels from stunned myocardium

Myocardial ischemia and reperfusion cause myocyte and vascular dysfunction, frequently termed "stunning." We hypothesized that inhibiting the Na(+)/H(+) exchanger subtype 1 isoform (NHE(1)) during ischemia and reperfusion limits myocardial and coronary microvascular stunning. Anesthetized rats completed 2 x 10-min coronary artery occlusions separated by 5-min of reperfusion, followed by 15 or 60 min of reperfusion. Vehicle (saline) or the NHE(1) inhibitor cariporide (HOE-642) was administered 15 min before ischemia and was continued throughout each protocol. After reperfusion, hearts were excised, and the reactivity of resistance arteries (internal diameter, approximately 120 microm) was assessed. The first derivative of left ventricular (LV) pressure, LV developed pressure, and LV systolic wall thickening were depressed (P < 0.05) similarly in vehicle- and cariporide-treated rats during ischemia and after 15 or 60 min of reperfusion compared with sham-operated animals that were not exposed to ischemia (i.e., controls). In vessels obtained after 15 min of reperfusion, the maximal response to acetylcholine-induced relaxation (10(-8)-10(-4) M) was blunted (P < 0.05) in vessels from vehicle- (approximately 35%) and cariporide-treated rats (approximately 55%) compared with controls (approximately 85%). However, the percent relaxation to acetylcholine was greater (P < 0.05) in cariporide-treated rats compared with vehicle-treated rats. Maximal contractile responses to endothelin-1 (10(-11)-10(-7) M) were increased (P < 0.05) similarly in vehicle- and cariporide-treated rats compared with controls. Relaxation to sodium nitroprusside (10(-4) M) was not different among groups. Results were similar in vessels obtained from animals after 60 min of reperfusion. These findings suggest that NHE(1) inhibition before coronary occlusion lessens ischemia-induced microvascular dysfunction for 15-60 min after reperfusion but does not alter myocardial contractile function in the area at risk.     

Increased plasma levels of adrenomedullin, a vasoactive peptide, in patients with end-stage pulmonary disease

AIM: To study adrenomedullin (AM) plasma levels in patients with severe lung disease and to analyze the relationship between AM and heart changes, hemodynamics and blood gases. METHODS: Case control study of 56 patients (36 men, 20 women) with severe lung disease and 9 control subjects (7 men, 2 women). Patients with end-stage pulmonary disease, including chronic obstructive pulmonary disease (COPD, n=11), cystic fibrosis (CF, 26), idiopatic pulmonary fibrosis (ILD, n=9), and idiopatic pulmonary arterial hypertension (PAH, n=10), who were evaluated for lung trasplantation between January 1997 and September 2000, and nine patients who underwent lung surgery for a solitary benign nodule. AM plasma levels in pulmonary artery (mixed venous blood, vein) and aorta or femoral artery (arterial, art), art and vein blood gases, pulmonary hemodynamics, systemic hemodynamics, two-dimensional transthoracic echocardiography and echo-Doppler study. RESULTS: Plasma AM (art and ven) levels were higher among patients' group compared to the controls (AMart p<0.02 and AMven p<0.04) for CF, ILD, PAH (AMart, pg ml(-1) Controls 13.7+/-3.6, COPD 22.8+/-6.2, CF 28.1+/-11.4, ILD 34.1+/-14.3, PAH 35.1+/-18.9; AMven, pg ml(-1) Controls 14.2+/-4.8, COPD 28.1+/-12.6, CF 31.7+/-14.1, ILD 38.7+/-16.5, PAH 40.1+/-4.4). We found with a trend towards higher concentration in ILD and PAH patients compared to COPD and CF but no statistical significant differences. Mixed-venous AM was higher than arterial AM in all groups resulting in AM uptake (AMPulmUp pg min(-1) Controls 4.8+/-22.6, COPD 21.1+/-44.9, CF 20.6+/-45.1, ILD 23.7+/-38.5, PAH 29.9+/-49.7). The univariate analysis showed a weak but significant correlation between AMart and mean systemic arterial pressure, heart rate, mean pulmonary arterial pressure and systemic vascular resistance. In the multivariate analysis, four variables emerged as independent factors of AMart including mean pulmonary arterial pressure, heart rate, mean systemic arterial pressure and left ventricular diastolic diameter (F=8.6, p<0.00001, r=0.60, r2=0.32). A similar weak correlation was apparent between AMven, systemic vascular resistance, and mean pulmonary arterial pressure. The results of multivariate analysis identify right atrial enlargement, mean right atrial pressure, heart rate and left ventricular dimensions as the only independent variables related to AMven (F=4.3, p<0.0004 r=0.56, r2=0.26). AM pulmonary uptake was significantly correlated with AMven (r=0.65), but not with hemodynamic, blood gas and echocardiographic variables. CONCLUSIONS: AM plasma levels are elevated in patients with severe lung disease in face of a preserved pulmonary uptake. These results suggest that the high AM plasma levels in patients with severe lung disease are not caused by a reduced pulmonary clearance, instead suggesting a systemic production.     

Activation and inactivation of volume-sensitive taurine efflux from rat mammary gland

Persistent left ventricular (LV) dysfunction after reperfused myocardial infarction (RMI) is a significant problem and angiotensin II (AngII) type 1 receptor (AT1R) blockers (ARBs) may limit reperfusion injury involving upregulation of AngII type 2 receptors (AT2R). To determine whether ARBs valsartan and irbesartan limit reperfusion injury and upregulate AT2R protein during RMI, we randomized dogs with anterior RMI (90 min ischemia; 120 min reperfusion) to 4 groups [valsartan (n = 6); irbesartan (n = 9); vehicle controls (n = 8); and sham (n = 6)] and measured serial in vivo hemodynamics, LV systolic and diastolic function, and inhibition of AngII pressor responses to the ARBs, and ex vivo infarct size, and regional AT1R and AT2R protein expression at the end of the reperfusion. Compared to the control group, both ARBs significantly limited the increase in left atrial pressure, promptly limited the deterioration of LV dP/dtmax, dP/dtmin, ejection fraction and diastolic function, limited infarct expansion and thinning, and limited infarct size. Importantly, both ARBs increased AT2R protein in the postischemic reperfused zone, with no change in AT1R protein. There were no changes in the sham group. The results suggest that limitation of myocardial injury associated with AT1R blockade combined with upregulation of AT2R protein expression contributes to the cardioprotective effects of ARBs during RMI. This beneficial effect of ARBs on persistent LV dysfunction after RMI should be evaluated in the clinical setting to determine the relative benefit of ARBs in patients who undergo reperfusion therapy for acute coronary syndromes.     

急性心肌梗死伴新发束支传导阻滞的临床意义

目的:观察急性心肌梗死伴新发左、右束支传导阻滞的临床特点,评价束支阻滞对急性心肌梗死预后的影响。方法:对上海交通大学附属第一人民医院心内科重症监护室2010年1月1日到12月31日收治的197例急性心肌梗死患者的病历资料进行回顾性分析,根据束支传导阻滞有无及类型分为左束支传导阻滞组(12例),右束支传导阻滞组(19例)和对照组(无束支传导阻滞的急性心梗,166例)。分析和比较三组患者的基线资料,心梗部位、Killip分级、恶性室性心律失常、左室射血分数LVEF、病变血管数量、梗死相关冠脉、住院天数及病死率、实验室检查(BNP,心肌损伤标志物峰值)。结果:LBBB组AMI患者的恶性心律失常发生率明显高于对照组(P=0.007),LVEF明显低于RBBB组和对照组(P值分别为0.020、0.045),梗死相关动脉以LAD多见。结论:急性心梗伴束支传导阻滞往往提示病情严重,预后不良,急性心梗合并左束支阻滞较合并右束支阻滞病情更严重。     

Enhanced early after-myocardial infarction concentration of TNF-alpha subsequently increased circulating and myocardial adrenomedullin in spontaneously hypertensive rats

Both inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) and the cardiac protective peptide adrenomedullin (AM) are increased in cardiac tissues and plasma in patients with myocardial infarction (MI) and chronic heart failure. Recently they have been increasingly recognized as important factors in the pathophysiology of MI and resultant congestive heart failure. Compared with sham-operated spontaneously hypertensive rats (SHR), we investigated myocardial immunoreactivity of TNF-alpha and AM and also their mutual relations in vivo in SHR+MI. Residual myocardial depression after MI was studied also in isolated perfused hearts. In chronic experiments, 24 and 48 h after permanent ligation of the descending anterior branch of the left coronary artery, we examined hemodynamics, plasma and myocardial peptide levels. Left ventricular function was assessed in isolated perfused hearts subjected to "global ischemia and reperfusion" and after induction of "calcium paradox". Circulating and myocardial TNF-alpha concentrations increased early after MI in SHR. Studies with global ischemia and calcium paradox in isolated heart showed early myocardial depression and calcium-dependent gradual increase of left-ventricular end-diastolic pressure. In the SHR+MI myocardial AM concentrations were increased 9- and 49-fold after respective 24 h and culminated 48 h following MI. Circulating and myocardial AM was increased in SHR+MI in association with TNFalpha-induced myocardial depression. The both studied cardiac parameters displayed the beneficial effect of the enhanced myocardial AM concentration.     

左心室脱血回注循环辅助法对急性心肌梗死血流动力学的改善作用

目的:实验观察左心室脱血回注循环辅助法对急性心肌梗死血流动力学的改善作用.方法:18只杂种犬分两组制作急性心肌梗死泵衰竭模型,治疗组给予左心室脱血回注循环辅助,对照组不进行治疗.观察比较两组间心律失常、死亡率、外周动脉压、肺动脉毛细血管楔嵌压(PCWP)、左心室舒张末期压(LVEDP)、左心室内径的变化.结果:治疗组室性期外收缩、心室纤颤发生率和死亡率显著低于对照组;对照组的外周动脉收缩压低于80 mmHg以下,治疗组维持在100mmHg以上(P＜0.01);治疗组PCWP和LVEDP值在45 min以后的各时段低于对照组(P＜0.01);治疗组的左室舒张末期内径小于对照组(P＜0.01).结论:左心室脱血回注循环辅助法能够减少急性心肌梗死泵衰竭的心室纤颤发生率和死亡率,有显著改善血流动力学、防止梗死后心肌扩张和有效的左心室辅助作用.     

急性心肌梗死高龄患者心肌灌注水平影响左室重构

为了探讨高龄急性心肌梗死(acute myocardial infarction, AMI)患者心脏超声特点,分析左室重构(left ventricle remodel, LVR)与心肌灌注水平的相关性,本研究选取2016年2月至2017年10月在广西医科大学第一附属医院治疗的高龄AMI患者104例,根据患者年龄分为A组49例(60~79岁)和B组55例(≥80岁),比较两组心脏超声指标,采用声学造影积分指数(contrast score index, CSI)评估两组术后心肌灌注水平。结果表明,B组后下壁心肌梗死比例为27.27%,明显高于A组(p<0.05);B组和A组前壁、下壁、前壁+下壁心肌梗死比例差异无统计学意义(p>0.05);B组左心室射血分数(left ventricular ejection fraction, LVEF)为(45.29±12.14)%,明显低于A组(p<0.05),左心房内径和左心室内径分别为(46.10径和左心室) mm和(57.29径和左心室内) mm,明显高于A组(p<0.05);B组经皮冠状动脉介入治疗(percutaneous coronary intervention,PCI)术后6个月CSI为(0.68±0.20),明显低于A组(p<0.05);B组术后左心房内径和左心室内径分别为(50.01±8.10) mm和(64.10±7.02) mm,明显高于A组(p<0.05);左心室内径与CSI呈负相关(r=-0.312, p<0.05)。综上表明,≥80岁患者与60~79岁患者心脏超声特点有所差异,年龄超过80岁的患者心功能以及PCI术后心肌灌注水平较差;心肌灌注水平与左室重构有一定相关性。     

High-molecular-weight polyethylene glycol protects cardiac myocytes from hypoxia- and reoxygenation-induced cell death and preserves ventricular function

Apoptosis plays a significant role in maladaptive remodeling and ventricular dysfunction following ischemia-reperfusion injury. There is a critical need for novel approaches to inhibit apoptotic cell death following reperfusion, as this loss of cardiac myocytes can progressively lead to heart failure. We investigated the ability and signaling mechanisms of a high-molecular-weight polyethylene glycol-based copolymer, PEG 15-20, to protect cardiac myocytes from hypoxia-reoxygenation (H-R)-induced cell death and its efficacy in preserving ventricular function following extended hypothermic ischemia and warm reperfusion as relevant to cardiac transplantation. Pretreatment of neonatal rat ventricular myocytes with a 5% PEG solution led to a threefold decline in apoptosis after H-R relative to untreated controls. There was a similar decline in caspase-3 activity in conjunction with inhibition of cytochrome c release from the inner mitochondrial membrane. Treatment with PEG also reduced reactive oxygen species production after H-R, and sarcolemmal lipid-raft architecture was preserved, consistent with membrane stabilization. Cell survival signaling was upregulated after H-R with PEG, as demonstrated by increased phosphorylation of Akt, GSK-3β, and ERK1/2. There was also maintenance of cardiac myocyte β-adrenergic signaling, which is critical for myocardial function. PEG 15-20 was very effective in preserving left ventricular function following prolonged hypothermic ischemia and warm reperfusion. PEG 15-20 has a potent protective antiapoptotic effect in cardiac myocytes exposed to H-R injury and may represent a novel therapeutic strategy to decrease myocardial cell death and ventricular dysfunction at the time of reperfusion during acute coronary syndrome or following prolonged donor heart preservation.     

Nicorandil in Patients with Acute Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis

Background

Nicorandil, as an adjunctive therapy with primary percutaneous coronary intervention (PCI), had controversial benefits in cardioprotection in patients with acute myocardial infarction (AMI).

Methods and Results

We performed a systematic review of randomized controlled trials (RCTs) comparing treatment with nicorandil prior to reperfusion therapy with control (placebo or no nicorandil) in patients who suffered from AMI and performed primary PCI. PubMed, EMBASE and CENTRAL databases and other sources were searched without language and publication restriction. 14 trials involving 1680 patients were included into this meta-analysis. Nicorandil significantly reduced the incidence of thrombolysis in myocardial infarction (TIMI) flow grade ≤2 (risk ratio [RR], 0.57; 95% confidence interval [CI]: 0.42 to 0.79), the Timi frame count (TFC) (mean difference [MD], -5.19; 95% CI: -7.13 to -3.26), increased left ventricular ejection fraction (LVEF) (%) (MD, 3.08; 95% CI: 0.79 to 5.36), and reduced the incidence of ventricular arrhythmia (RR, 0.53; 95% CI: 0.37 to 0.76) and congestive heart failure (CHF) (RR, 0.41; 95% CI: 0.22 to 0.75). No difference in the pear creatine kinase (CK) value (MD, -290.19; 95% CI: -793.75 to 213.36) or cardiac death (RR, 0.39; 95% CI: 0.09 to 1.67) was observed.

Conclusions

Nicorandil prior to reperfusion is associated with improvement of coronary reflow as well as suppression of ventricular arrhythmia, and further improves left ventricular function in patients who suffered from AMI and underwent primary PCI. But the definite clinical benefits of nicorandil were not found, which may be due to the small sample size of the selected studies.     

Matrix metalloproteinases and collagen ultrastructure in moderate myocardial ischemia and reperfusion in vivo

Severe ischemic injury or infarction of myocardium may cause activation of matrix metalloproteinases (MMPs) and damage the interstitial matrix. However, it is unknown whether MMP activation and matrix damage occur after moderate ischemia and reperfusion that result in myocardial stunning without infarction, and if so whether such changes contribute to postischemic myocardial expansion and contractile dysfunction. To address these questions, open-chest anesthetized pigs underwent 90 min of regional ischemia (subendocardial blood flow 0.4 +/- 0.1 ml. g(-1). min(-1)) and 90 min of reperfusion. After ischemia plus reperfusion, histological and ultrastructural examination revealed no myocardial infarction or inflammatory cell infiltration. Myocardial MMP-9 content increased threefold with a fourfold increase in the active form (P < 0.001). Myocardial collagenase content doubled (P < 0.01) but remained in latent form. MMP-2 and tissue inhibitors of metalloproteinases were unaffected. Despite increases in MMPs, collagen ultrastructure (assessed by cell maceration scanning electron microscopy) was unaltered. Intracoronary administration of the MMP inhibitor GM-2487 did not prevent or attenuate myocardial expansion (assessed by regional diastolic dimensions at near-zero left ventricular pressure) or contractile dysfunction. We conclude that although moderate ischemia and reperfusion alter myocardial MMP content and activity, these effects do not result in damage to interstitial collagen, nor do they contribute to myocardial expansion or contractile dysfunction.     

Cardiac magnetic resonance imaging of myocardial contrast uptake and blood flow in patients affected with idiopathic or familial dilated cardiomyopathy

Idiopathic dilated cardiomyopathy (IDC) is characterized by left ventricular (LV) enlargement with systolic dysfunction, other causes excluded. When inherited, it represents familial dilated cardiomyopathy (FDC). We hypothesized that IDC or FDC would show with cardiac magnetic resonance (CMR) increased myocardial accumulation of gadolinium contrast at steady state and decreased baseline myocardial blood flow (MBF) due to structural alterations of the extracellular matrix compared with normal myocardium. CMR was performed in nine persons affected with IDC/FDC. Healthy controls came from the general population (n = 6) or were unaffected family members of FDC patients (n = 3) without signs or symptoms of IDC/FDC or any structural cardiac abnormalities. The myocardial partition coefficient for gadolinium contrast (lambda(Gd)) was determined by T1 measurements. LV shape and function and MBF were assessed by standard CMR methods. lambda(Gd) was elevated in IDC/FDC patients vs. healthy controls (lambda(Gd) = 0.56 +/- 0.15 vs. 0.41 +/- 0.06; P = 0.002), and correlated with LV enlargement (r = 0.61 for lambda(Gd) vs. end-diastolic volume indexed by height; P < 0.01) and with ejection fraction (r = -0.80; P < 0.001). The extracellular volume fraction was higher in IDC patients than in healthy controls (0.31 +/- 0.05 vs. 0.24 +/- 0.03; P = 0.002). Resting MBF was lower in IDC patients (0.64 +/- 0.13 vs. 0.91 +/- 0.22; P = 0.01) than unaffected controls and correlated with both the partition coefficient (r = -0.57; P = 0.012) and the extracellular volume fraction (r = -0.56; P = 0.019). The expansion of the extracellular space correlated with reduced MBF and ventricular dilation. Expansion of the extracellular matrix may be a key contributor to contractile dysfunction in IDC patients.     

The Radiation Issue in Cardiology: the time for action is now

Background

The study was designed to evaluate whether the preserved coronary flow reserve (CFR) 72 hours after reperfused acute myocardial infarction (AMI) is associated with less microvascular dysfunction and is predictive of left ventricular (LV) functional recovery and the final infarct size at follow-up.

Methods

In our study, CFR was assessed by transthoracic Doppler echocardiography (TDE) in 44 patients after the successful percutaneous coronary intervention during the acute AMI phase. CFR was correlated with contractile reserve assessed by low-dose dobutamine echocardiography and with the total perfusion defect measured by single-photon emission computed tomography 72 hours after reperfusion and at 5 months follow-up. The ROC analysis was performed to determine test sensitivity and specificity based on CFR. Categorical data were compared by an χ² analysis, continuous variables were analysed with the independent Student's t test. In order to analyse correlation between CFR and the parameters of LV function and perfusion, the Pearson correlation analysis was conducted. The linear regression analysis was used to assess the relationship between CFR and myocardial contractility as well as the final infarct size.

Results

We estimated the CFR cut-off value of 1.75 as providing the maximal accuracy to distinguish between patients with preserved and impaired CFR during the acute AMI phase (sensitivity 91.7%, specificity 75%). Wall motion score index was better in the subgroup with preserved CFR as compared to the subgroup with reduced CFR: 1.74 (0.29) vs. 1.89 (0.17) (p < 0.001) during the acute phase and 1.47 (0.30) vs. 1.81 (0.20) (p < 0.001) at follow-up, respectively. LV ejection fraction was 47.78% (8.99) in preserved CFR group vs. 40.79% (7.25) in impaired CFR group (p = 0.007) 72 hours after reperfusion and 49.78% (8.70) vs. 40.36% (7.90) (p = 0.001) after 5 months at follow-up, respectively. The final infarct size was smaller in patients with preserved as compared to patients with reduced CFR: 5.26% (6.14) vs. 23.28% (12.19) (p < 0.001) at follow-up.

Conclusion

The early measurement of CFR by TDE can be of high value for the assessment of successful reperfusion in AMI and can be used to predict LV functional recovery, myocardial viability and the final infarct size.