Prevalent platelet dysfunction in patients with aortic valve disease.

BACKGROUND AND AIM OF THE STUDY: In patients with heart valve disease, the valve leaflets display a gapped, rough endothelial lining often covered with calcified areas. As a consequence, blood flow is disturbed and a stimulation of components of the hemostasis system is assumed. The possible mechanisms of this process are, however, unclear at present. METHODS: Platelet function was studied in 660 patients considered for isolated coronary artery bypass graft (CABG) surgery, and in 421 patients considered for single aortic valve replacement (AVR). Platelet function was monitored preoperatively using the platelet function analyzer device (PFA-100). The test results were reported as closure time of the membrane hole at the end of a capillary tube. The von Willebrand factor antigen, and its collagen-binding activity, were also determined among subgroups of 40 AVR and 50 CABG candidates. RESULTS: Platelet dysfunction was displayed by only 22% of CAD patients, but by 83% of AVR candidates. The mean PFA closure time in AVR patients was considerably higher than in CAD patients (231 +/- 59 s versus 153 +/- 60 s, respectively; p < 0.01). The mean platelet volume, platelet distribution width and von Willebrand factor collagen binding and antigen levels did not differ between the patient groups. CONCLUSION: It is assumed that, due to disturbed flow and shear exposition, following an initial activation, the platelets are partially degranulated, shed microparticles, and might become involved in the pathogenesis of microvascular dysfunction and thrombotic events in patients with aortic valve disease.

Cardiac efficiency and oxygen consumption measured with 11C-acetate PET after long-term cardiac resynchronization therapy.

UNLABELLED: Cardiac resynchronization therapy (CRT) is a treatment option in patients with severe heart failure and left bundle-branch block (LBBB). This study evaluated the effects of 4 and 13 mo of CRT on myocardial oxygen consumption (MVO2) and cardiac efficiency as compared with mild heart failure patients without LBBB. METHODS: Sixteen patients with severe heart failure and LBBB due to idiopathic cardiomyopathy were studied at baseline and after 4 and after 13 mo of therapy. Thirteen patients with mild heart failure without LBBB served as a comparison group. The clearance rate (k2) of 11C-acetate was measured with PET to assess MVO2. Stroke volume was derived from the dynamic PET data according to the Stewart-Hamilton principle and, furthermore, cardiac efficiency using the work metabolic index. RESULTS: After 4 mo of CRT, stroke volume index (SVI) increased by 50% (P = 0.012) and cardiac efficiency increased by 41% (P < 0.001). Global k2 remained unchanged but regional k2 demonstrated a more homogeneous distribution pattern. The parameters showed no significant changes during therapy. Under CRT, cardiac efficiency, SVI, and the distribution pattern of regional k2 did not differ from mild heart failure patients without LBBB. CONCLUSION: CRT improves cardiac efficiency for at least 13 mo, as demonstrated by a higher SVI, whereas MVO2 remains unchanged. Cardiac efficiency, SVI, and the MVO2 distribution pattern reach the level of patients with mild heart failure without LBBB. The unfavorable hemodynamic performance in heart failure with LBBB is effectively restored by long-term CRT to the level of an earlier disease state.

Beneficial effects of atorvastatin on myocardial regions with initially low vasodilatory capacity at various stages of coronary artery disease.

PURPOSE: The aim of this study was to analyse non-invasively the regional effect of therapy with an HMG-CoA reductase inhibitor on myocardial blood flow in patients with coronary artery disease (CAD) with special reference to segments with initially substantially impaired vasodilation. METHODS: The study included 26 patients with untreated hypercholesterolaemia. Coronary angiography revealed CAD in nine patients with stenosis >50% and wall irregularities or minimal stenosis <30% in 17 patients. Before and 4.6+/-1.8 months after atorvastatin therapy, ( 13)N-ammonia positron emission tomography (PET) studies were performed at rest and under pharmacological stress. Minimum coronary vascular resistance (MCR) and coronary flow reserve (CFR) were determined. Segments were divided into those with normal or near-normal (MBF during adenosine > or =2.0 ml/min/g) and those with abnormal (MBF<2.0 ml/min/g) vasodilator flow response. In CAD patients, 156 segments were analysed, 85 of which had abnormal MBF; in the non-obstructive group, 59 of 297 segments had abnormal MBF. RESULTS: LDL cholesterol decreased after atorvastatin therapy from 186+/-43 mg/dl to 101+/-26 mg/dl (p<0.001). In normal segments no significant changes in MBF, CFR and MCR were found. However, initially abnormal segments showed significant improvements in MCR (15%, p<0.0001) and MBF during adenosine (30%, p<0.0001) after therapy. CONCLUSION: The improvement in regional coronary vasodilator function after atorvastatin in patients with coronary atherosclerosis may be caused, at least in part, by increased flow-mediated (endothelium-dependent) dilation of the total arteriolar and arterial vascular system. These data further support the concept of non-invasive management of stable CAD by statin therapy and life-style modification guided by PET.

Global and regional myocardial oxygen consumption and blood flow in severe cardiomyopathy with left bundle branch block.

OBJECTIVE: In patients with dilated cardiomyopathy (DCM), left bundle branch block (LBBB) is a common finding. The characteristic feature is an asynchronous septal wall motion and most frequently a delay of the lateral and/or posterior wall segments. With the onset of cardiac resynchronization therapy, there is a focus on the specific pathophysiology of a LBBB. However, quantitative data on regional myocardial oxygen consumption (MVO(2)) and blood flow (MBF) are missing. METHODS: We studied 31 patients with severe DCM and LBBB (ejection fraction 22.1+/-7.1%) and 14 patients with mild to moderate DCM without LBBB (ejection fraction 46.7+/-7.9%). Global and regional MVO(2) as well as MBF were determined from a dynamic (11)C-acetate positron emission tomography (PET) study. RESULTS: Global MVO(2) and MBF were lower in the DCM group with LBBB than in the control group (P<0.05). Regionally, the LBBB group revealed a higher (P<0.05) MVO(2) and MBF in the lateral wall than in the other walls. The control group did not show significant differences between the myocardial walls and demonstrated a smaller variability of the parameters. CONCLUSION: DCM patients with LBBB exhibit a more heterogeneous distribution of MVO(2) and MBF among the myocardial walls than DCM patients without LBBB. Due to the LBBB associated electromechanical alterations, the highest regional values of MVO(2) and MBF are found in the lateral wall.

Effect of cardiac resynchronization therapy on global and regional oxygen consumption and myocardial blood flow in patients with non-ischaemic and ischaemic cardiomyopathy.

AIMS: We studied the effects of cardiac resynchronization therapy (CRT) on global and regional myocardial oxygen consumption (MVO2) and myocardial blood flow (MBF) in non-ischaemic (NICM) and ischaemic dilated cardiomyopathy (ICM). METHODS AND RESULTS: Thirty-one NICM and 11 ICM patients, all of them acute responders, were investigated. MVO2 and MBF were obtained by 11C-acetate PET before and after 4 months of CRT. In NICM global MVO2 and MBF did not change during CRT, while the rate pressure product (RPP) normalized MVO2 increased (P=0.03). Before CRT regional MVO2 and MBF were highest in the lateral wall and lowest in the septum. Under therapy, MVO2 and MBF decreased in the lateral wall (P=0.045) and increased in the septum (P=0.045) resulting in a more uniform distribution. In ICM, global MVO2, MBF, and RPP did not change under CRT. Regional MVO2 and MBF showed no significant changes but a similar tendency in the lateral and septal wall to that in NICM. CONCLUSION: CRT induces changes of MVO2 and MBF on a regional level with a more uniform distribution between the myocardial walls and improved ventricular efficiency in NICM. Based on the investigated parameters, CRT appears to be more effective in NICM than in ICM.

[123I]-phenylpentadecanoic acid uptake in patients with dilated cardiomyopathy.

BACKGROUND: The rate constant for global fatty acid influx (k(1)) was studied in 12 male patients with dilated cardiomyopathy (DCM). METHOD: 10 normal subjects served as controls. 201-Thallium (201TI) and [123I]-phenyl-pentadecanoic acid (IPPA) were administered during bicycle exercise under fasting conditions. RESULTS: All patients showed non-homogeneous tracer uptake defects for 201TI and IPPA. k(1) was significantly higher in DCM patients than controls. k(1) showed significant inverse correlation between cardiac index, left-ventricular ejection fraction, left-ventricular enddiastolic pressure and echocardiographic left-ventricular ejection fraction. CONCLUSION: We presume that an increased regional rate constant of IPPA influx into the myocardial tissue in patients with DCM reflects a compensatory mechanism of altered myocardium.