Cardiac ß-Adrenergic Receptor Downregulation, Evaluated by Cardiac PET, in Chronotropic Incompetence.

The mechanism of chronotropic incompetence (CTI), which has been associated with autonomic dysfunction, has not been elucidated in patients without heart failure (HF). Methods: Cardiac PET using 11C-CGP12177 was performed to investigate the cardiac ß-adrenergic receptor density (ß-ARD) in 13 patients with CTI without HF and 6 healthy controls. The maximum number of available specific 11C-CGP12177 binding sites per gram of tissue was calculated in regions of interest using an established graphical method. Results: Peak heart rate was significantly lower in CTI patients than in controls (116.9 ± 11.0 vs. 154.8 ± 14.4 beats/min, P < 0.001). ß-ARD of the total myocardium was significantly lower in CTI patients than in controls (4.3 ± 1.7 vs. 7.0 ± 1.7 pmol/mL, P = 0.005). Conclusion: ß-adrenergic receptor downregulation was demonstrated in patients with CTI without HF. Decreased ß-ARD is a common feature in patients with CTI, with or without HF.

Long-term survival of patients with pulmonary arterial hypertension recovering to World Health Organization functional class I or II: a historical comparison between intravenous epoprostenol and oral agents.

BACKGROUND: Intravenous epoprostenol is the only drug proved in a randomized study to reduce mortality in patients with idiopathic pulmonary arterial hypertension (PAH). However, administration of this drug has procedural difficulties and a risk of sepsis. Oral drugs provide simple treatment, but their benefit for survival has not been proven. A recovery of patients with PAH to World Health Organization functional class (WHO-FC) I or II may predict favorable survival. METHODS: Survival analyses were performed on a historical cohort of 41 patients with PAH. The patients were 43 ± 22 years old, 23 had idiopathic or heritable PAH, and 18 had connective tissue disease-associated PAH. The baseline was defined as the initial visit to a medical facility. RESULTS: The median duration of follow-up was 1276 days (108 to 5389 days) and 21 patients died during this period. The estimated survival times for patients who received intravenous epoprostenol and did and did not recover to WHO-FC I or II were 4371 ± 577 days and 1172 ± 404 days, respectively. These times for patients who were not treated with intravenous epoprostenol and did and did not recover to WHO-FC I or II were 4717 ± 554 days and 925 ± 230 days, respectively. A Cox proportional hazard analysis gave a hazard ratio for death after recovery to WHO-FC I or II of 0.07 (P < 0.001). In contrast, use of intravenous epoprostenol was not a significant factor affecting survival (P = 0.96). CONCLUSIONS: Patients with PAH who achieve recovery to WHO-FC I or II without use of intravenous epoprostenol have similar survival to those who reach the same WHO-FC with use of intravenous epoprostenol. Benign survival of patients with PAH who have recovered to WHO-FC I or II may extend for several years after onset of the disease.

[Cardiovascular performance assessed with exercise testing].

Since the first exercise electrocardiography was recorded in 1908, it has been in widespread clinical use for more than 100 years. Exercise testing can be performed easily and noninvasively and is relatively inexpensive. This testing is generally safe but myocardial infarction and death occur rarely. The Japanese Circulation Society describes the wide applications of exercise testing in the guidelines. The guideline for ischemic heart disease prioritizes exercise testing for the diagnosis of stable angina pectoris. Although the sensitivity and specificity are not as high as other noninvasive testing (i.e., stress single-photon emission computed tomography, computed tomography and MRI), exercise testing can also assess the severity and prognosis of the disease. Cardiac rehabilitation is a useful tool to improve the prognosis of patients with myocardial infarction. Exercise therapy is a main component of cardiac rehabilitation, and exercise testing is indispensable for prescribing exercise therapy. Exercise capacity is an important prognostic factor in patients with heart failure. The guideline for the diagnosis of chronic heart failure recommends cardiopulmonary exercise testing to evaluate exercise capacity.

Cardiac ß-adrenergic receptor density and myocardial systolic function in the remote noninfarcted region after prior myocardial infarction with left ventricular remodelling.

PURPOSE: After myocardial infarction (MI), left ventricular (LV) remodelling is observed in noninfarcted LV myocardium. LV remodelling is closely associated with systolic heart failure. Since myocardial dysfunction is related to the downregulation of cardiac postsynaptic beta-adrenergic receptors (ß-AR), we hypothesized that a reduction in ß-AR density may be manifested in the remote noninfarcted region and such reduction may be related to myocardial systolic dysfunction. Accordingly, we assessed ß-AR density with a focus on the remote noninfarcted region. METHODS: Cardiac PET was performed in 15 patients with a prior MI and 10 age-matched healthy controls using (11)C-CGP 12177, a radioligand for ß-receptors. The maximum number of available specific (11)C-CGP 12177 binding sites per gram of tissue was calculated in regions of interest using an established graphical method. LV regional systolic function was assessed based on peak systolic myocardial strain on the LV wall in the longitudinal direction using two-dimensional ultrasound speckle tracking imaging. LV volumes and LV ejection fraction (EF) were also measured. RESULTS: The LV end-diastolic volume index was significantly larger in patients than in controls (67.8 ± 16.9 vs. 49.1 ± 12.3 ml/m(2), p < 0.01). Significant differences in ß-AR density were observed among three areas: the apical area in controls (where the lowest ß-AR density was observed), the remote noninfarcted region of patients and LVEF ≥ 55 %, and the remote noninfarcted region of patients and LVEF <55 % (5.8 ± 2.1 vs. 4.2 ± 0.7 vs. 3.3 ± 0.7 pmol/ml, p < 0.01, ANOVA). Peak systolic myocardial strain was significantly reduced in the remote noninfarcted LV wall in patients with a prior anterior wall MI compared with that in the corresponding wall in controls (-15.5 ± 2.5 vs. -20.1 ± 2.2 %, p < 0.001). A similar finding was also observed in patients with a prior inferior wall MI. CONCLUSION: In the remote noninfarcted region in patients, ß-AR downregulation was observed, which was related to deterioration of local myocardial systolic function.

Pulmonary venous occlusion and death in pulmonary arterial hypertension: survival analyses using radiographic surrogates.

BACKGROUND: Recent studies find that a considerable number of patients with pulmonary arterial hypertension (PAH) develop fibrous obstruction of the pulmonary veins. Such obstruction more commonly accompanies connective tissue disorder (CTD)-associated PAH than idiopathic PAH. However, few researchers have gauged the risk of death involving obstruction of the pulmonary veins. METHODS: Thirty-seven patients with PAH were enrolled (18 patients, idiopathic PAH; 19 patients, CTD-associated PAH). The patients were 49 ± 18 years and had a World Health Organization functional class of 3.2 ± 0.6. Thickening of the interlobular septa, centrilobular ground-glass attenuation, and mediastinal adenopathy were surrogates for obstruction of the pulmonary veins, and were detected by a 16-row multidetector computed tomography scanner. RESULTS: The follow-up period was 714 ± 552 days. Fifteen deaths occurred. Thickening of the interlobular septa, centrilobular ground-glass attenuation, and mediastinal adenopathy were found in 37.8%, 24.3%, and 16.2% of patients, respectively. Cox proportional hazard analysis revealed an increased risk of death with each radiographic surrogate (mediastinal adenopathy: p < 0.0001, hazard ratio = 13.9; thickening of interlobular septa: p < 0.001, hazard ratio = 12.0; ground-glass attenuation: p = 0.02, hazard ratio = 3.7). The statistical significance of these relationships was independent of the cause of PAH and plasma concentration of brain natriuretic peptide. CONCLUSIONS: The results of this study imply that obstruction of the pulmonary veins is associated with an increased risk of death in patients with PAH.

Myocardial fiber shortening in the circumferential direction produces left ventricular wall thickening during contraction.

When one bends the elbow by shortening of the biceps, a knot of muscle is observed in his or her upper arm, indicating that muscle shortening is converted to muscle standing in the perpendicular direction due to the incompressibility of skeletal muscle. A similar mechanism may work in the thickening process of the left ventricular (LV) wall. Although myocardial fibers of the left ventricle shorten by about 20% along the fiber direction when they contract, thickening of the LV wall during contraction often exceeds 50%. Thus, the aim of the present study was to clarify the mechanism by which myocardial fiber shortening produces such remarkable thickening of the LV wall. We hypothesized that myocardial fiber shortening in the circumferential direction causes myocardial transformation perpendicular to the fiber direction, thereby producing LV wall thickening. We evaluated this hypothesis using an incompressible model of the LV wall. In 15 healthy male volunteers (38±13 years), we calculated theoretical peak thickening values of the inner and outer LV wall layers and compared them with directly measured peak thickening values using Doppler strain imaging at the corresponding areas. The theoretical peak thickening and directly measured peak thickening were >60% in the LV inner layer. The theoretical peak thickening was correlated with the directly measured peak thickening in the inner (r=0.75, p<0.05) and outer (r=0.61, p<0.05) layers. We conclude that shortening of LV circumferential myocardial fiber and incompressibility of myocardium produce LV wall thickening during contraction.

Bilirubin as a prognostic marker in patients with pulmonary arterial hypertension.

BACKGROUND: Liver dysfunction reflects the status of heart failure, with congestion and low perfusion of the liver serving as causative mechanisms. Previous studies demonstrated relationship between the results of liver function test and the prognosis in patients with heart failure. However, few studies have examined this relationship in patients with pulmonary arterial hypertension (PAH). METHODS: The subjects were 37 patients with PAH (8 men and 29 women; 18 with idiopathic PAH and 19 with connective tissue disease-associated PAH). A blood test was performed after a 3-month period free from hospitalization and without changes in functional class, treatment, heart sounds, body weight, or heart rate. RESULTS: In a mean follow-up period of 635 +/- 510 days, 12 patients died due to heart failure, 2 died due to pulmonary hemorrhage, and 23 patients survived. Cox proportional hazard analyses identified functional class (p < 0.001), plasma concentration of brain natriuretic peptide (BNP) (p = 0.001), and hyperbilirubinemia (serum total bilirubin > 1.2 mg/dL; p < 0.001; hazard ratio = 13.31) as predictors of mortality. Patients with hyperbilirubinemia had a worse functional class (P = 0.003), a higher right atrial pressure (p < 0.001), a higher plasma concentration of BNP (p = 0.004), and a larger Doppler right ventricular index of the right ventricle (p = 0.041). CONCLUSION: Elevated serum bilirubin is a risk factor for death in patients with PAH.

Left ventricular remodeling after myocardial infarction impairs early diastolic, but not systolic, function in the radial direction in the remote normal region.

BACKGROUND: It is acknowledged that expansion of the remote normal region of the left ventricle causes remodeling after myocardial infarction (MI). However, the characteristics of that region have not been fully elucidated. METHODS: We studied 13 patients with atypical chest pain (controls) and 15 patients with a prior anterior MI who underwent cardiac catheterization. With Doppler strain imaging, we measured the peak radial myocardial systolic strain and peak radial early diastolic strain rate at the posterior wall of the left ventricle. None of the patients with atypical chest pain exhibited significant stenosis of the three major coronary arteries or left ventricular (LV) wall motion abnormality in cardiac catheterization. The patients with a prior anterior MI had single anterior descending artery disease without wall motion abnormality in the LV inferoposterior wall. LV ejection fraction and the LV relaxation time constant were also measured. RESULTS: The LV ejection fraction was significantly smaller in patients with a prior MI compared to controls. The peak radial systolic strain in the LV posterior wall was not significantly different between the patients with a prior MI and controls (125 ± 49 vs. 122 ± 29%). In contrast, the peak radial early diastolic strain rate in the same area was significantly lower in the patients with a prior MI than in controls (-7.4 ± 2.7 vs. -13.2 ± 4.0 s(-1), p < 0.001). Peak early diastolic radial strain rate was significantly correlated with the LV relaxation time constant in all patients (r = 0.69, p < 0.001). CONCLUSION: LV remodeling after an MI impairs local early diastolic myocardial function in the remote normal region and it is related to global LV diastolic dysfunction.

Correlation between left ventricular end-diastolic pressure and peak left atrial wall strain during left ventricular systole.

OBJECTIVE: Left atrial (LA) reservoir function is determined by integration of LA relaxation and left ventricular (LV) systolic function, and LV diastolic dysfunction increases LA volume at end systole. This study investigates the effect of LV end-diastolic pressure on LA wall tension during LV systole. METHODS: A total of 101 stable patients with sinus rhythm undergoing cardiac catheterization were studied. LA wall extension during LV systole was evaluated as LA wall strain in the longitudinal direction obtained using two-dimensional ultrasound speckle tracking imaging. LV end-diastolic pressure and LV end-systolic and end-diastolic volumes were obtained in cardiac catheterization, and LV ejection fraction was determined. RESULTS: Peak LA wall strain during LV systole had a significant inverse correlation with LV end-diastolic pressure (r = - 0.76, P < .0001). This correlation was also significant in patients with preserved LV systolic function (LV ejection fraction > or =50%) (r = - 0.64, P < .0001). In patients with peak LA wall strain during LV systole of less than 30%, 89% had elevated LV end-diastolic pressure (> or =16 mm Hg). CONCLUSION: Elevated LV end-diastolic pressure is associated with a decrease of peak LA wall strain in the longitudinal direction during LV systole. In patients with peak LA wall strain during LV systole of less than 30%, the majority had elevated LV end-diastolic pressure, while most patients with peak LA wall strain during LV systole 45% or higher had normal LV end-diastolic pressures. In patients whose LV ejection fraction is 50% or more, when peak LA wall strain during LV systole is between 30% and 44%, it is not possible to predict LV end-diastolic pressure from peak LA wall strain measures.

Impaired myocardial oxidative metabolism in the remote normal region in patients in the chronic phase of myocardial infarction and left ventricular remodeling.

BACKGROUND: Left ventricular (LV) remodeling occurs in the remote normal region in the LVs after myocardial infarction (MI) and is closely involved in heart failure. METHODS: We assessed myocardial oxygen consumption using a clearance rate constant K (mono) for the time activity curves of (11)C-acetate in 15 patients with a prior anterior wall MI, 8 with a prior inferior wall MI, and 10 age-matched normal control subjects. LV end-systolic volume index (ESVI) was determined by echocardiography. RESULTS: The LVESVI was significantly greater in patients with an anterior and inferior MI than in control subjects. The heart rate systolic pressure product did not differ among the groups. K (mono) in the remote normal region in patients with an anterior MI was significantly less than that in the corresponding area in control subjects (0.055 +/- 0.005 vs 0.065 +/- 0.008 min(-1), P < .001). K (mono) in the remote normal region in those with an inferior MI was also significantly less compared with controls (0.054 +/- 0.007 vs 0.069 +/- 0.010 min(-1), P < .01). CONCLUSION: In patients with a prior MI and LV remodeling, myocardial oxidative metabolism is apparently impaired in the remote normal region where augmented myocardial energy production is needed against the increased end-systolic wall stress caused by LV dilatation.

Peak mitral annular velocity during early diastole and propagation velocity of early diastolic filling flow are not interchangeable as the parameters of left ventricular early diastolic function.

The difference between peak mitral annular velocity during early diastole (Ea) and the propagation velocity of left ventricular (LV) early diastolic filling flow (Vp) obtained using Doppler imaging as LV relaxation parameters was not fully elucidated. Thus, this issue was investigated in 117 patients with suspected coronary artery disease. During cardiac catheterization, LV volumes, the LV relaxation time constant Tp, and inertia force of late systolic aortic flow were obtained. Ea significantly and closely correlated with Tp (r = -0.70, p <0.0001) and significantly but weakly correlated with LV ejection fraction (r = 0.37, p <0.0001) and inertia force (r = 0.34, p = 0.0002). Conversely, Vp significantly and closely correlated with both LV ejection fraction (r = 0.66, p <0.0001) and inertia force (r = 0.72, p <0.0001) and significantly but weakly correlated with Tp (r = - 0.35, p = 0.0001). In conclusion, Ea and Vp reflect different aspects of LV behavior from end-systole to early diastole. Ea can be used to index LV relaxation, whereas Vp might not be a proper parameter of LV intrinsic relaxation because it is significantly dependent on LV systolic function and LV chamber size at end-systole. Both parameters are not interchangeable as those of LV early diastolic function. Vp may be a noninvasive parameter of LV elastic recoil.

Lack of inertia force of late systolic aortic flow is a cause of left ventricular isolated diastolic dysfunction in patients with coronary artery disease.

OBJECTIVES: We investigated whether a lack of inertia force of late systolic aortic flow and/or apical asynergy provoke early diastolic dysfunction in patients with coronary artery disease (CAD). BACKGROUND: Left ventricular (LV) isolated diastolic dysfunction is a well-recognized cause of heart failure. METHODS: We evaluated LV apical wall motion and obtained left ventricular ejection fraction (LVEF) by left ventriculography in 101 patients who underwent cardiac catheterization to assess CAD. We also computed the LV relaxation time constant (Tp) and the inertia force of late systolic aortic flow from the LV pressure (P)-first derivative of left ventricular pressure (dP/dt) relation. Using color Doppler echocardiography, we measured the propagation velocity of LV early diastolic filling flow (Vp). Patients with LVEF > or =50% (preserved systolic function [PSF], n = 83) were divided into 2 subgroups: patients with inertia force (n = 53) and without inertia force (n = 30). No patient with systolic dysfunction (SDF) (LVEF <50%) had inertia force (n = 18). RESULTS: The Tp was significantly longer in patients with SDF (85.7 +/- 21.0 ms) and with PSF without inertia force (81.1 +/- 23.6 ms) than in those with PSF with inertia force (66.3 +/- 12.8 ms) (p< 0.001). The Vp was significantly less in the former 2 groups than in the last group. In patients with PSF, LV apical wall motion abnormality was less frequently observed in those with inertia force than in those without (p < 0.0001). CONCLUSIONS: An absence of inertia force in patients with PSF is one of the causes of isolated diastolic dysfunction in patients with CAD. Normal LV apical wall motion is substantial enough to give inertia to late systolic aortic flow.

Sequence analysis of three plasmids harboured in Rhodococcus erythropolis strain PR4.

Rhodococcus erythropolis strain PR4 has been isolated as an alkane-degrading bacterium. The strain harbours one linear plasmid, pREL1 (271 577 bp) and two circular plasmids, pREC1 (104 014 bp) and pREC2 (3637 bp), all with some sequence similarities to other Rhodococcus plasmids. For pREL1, pREC1 and pREC2, 298, 102 and 3 open reading frames, respectively, were predicted. Linear plasmid pREL1 has several regions homologous to plasmid pBD2 found in R. erythropolis BD2. Sequence analysis of pREL1 and pBD2 identified common metal-resistance genes on both, but pREL1 also encodes alkane-degradation genes not found on pBD2, with enzyme constituents some of which are quite different from those of other organisms. The alkane hydroxylase consisted of a cytochrome P450 monooxygenase, a 2Fe-2S ferredoxin, and a ferredoxin reductase. The ferredoxin reductase amino acid sequence resembles the AlkT (rubredoxin reductase) sequence. A zinc-containing alcohol dehydrogenase further oxydizes alkanols, alkane oxidation products catalysed by alkane hydroxylase. Of the circular plasmids, the pREC1 sequence is partially similar to the sequence of pREAT701, the virulence plasmid found in Rhodococcus equi. pREC1 has no pREAT701 virulence genes and encodes genes for beta-oxidation of fatty acids. Thus, joint actions of enzymes encoded by pREL1 and pREC1 may enable efficient mineralization of alkanes.

Evaluation of fatty acid beta-oxidation in patients with prior myocardial infarction in relation to myocardial blood flow, total oxidative metabolism, and left ventricular wall motion.

BACKGROUND: Fatty acid metabolism in patients with myocardial infarction (MI) who undergo coronary reperfusion has not been fully elucidated and was investigated in the present study using positron emission tomography. METHODS AND RESULTS: The clearance rate constant of 11C-acetate (acetate-Kmono) and that of 11C-palmitate (palmitate-Kmono) from the myocardium were calculated using a monoexponential equation in 14 patients with MI. A total of 155 regions of interest were classified based on coefficient of determination (R2) values of monoexponential curves for 11C-palmitate clearance: well fitted regions (R2>or=0.5) and poorly fitted regions (R2<0.5). Regional relative myocardial blood flow calculated from the initial distribution of 11C-acetate and left ventricular (LV) wall motion were also evaluated. Peak 11C-palmitate uptake (14,434+/-3,052 vs 12,016+/-3,088 counts/s, p<0.001) and percent clearance during acquisition (38.2+/-10.1 vs 23.6+/-11.4%, p<0.001) were significantly greater in the well fitted regions (n=111) than in the poorly fitted regions (n=44). Acetate-Kmono was significantly higher in the former than in the latter (0.0641+/-0.0099 vs 0.0476+/-0.0103 min-1, p<0.001). LV wall motion and regional relative blood flow were also significantly greater in the former regions. Palmitate-Kmono in the well fitted regions was significantly higher in normal LV wall motion areas than in hypokinesis areas (0.0363+/-0.0062 vs 0.0274+/-0.0057 min-1, p<0.001) CONCLUSIONS: Maintenance of myocardial fatty acid beta-oxidation with better myocardial blood flow is substantial in the preservation of total myocardial oxidative metabolism and LV wall motion in patients with MI. The finding that the early-phase clearance of 11C-palmitate is fitted with a monoexponential curve may provide important information in the evaluation of myocardial fatty acid beta-oxidation.

Evaluation of whole left ventricular systolic performance and local myocardial systolic function in patients with prior myocardial infarction using global long-axis myocardial strain.

Left ventricular (LV) global strain along its long axis during systole, which is obtained by dividing mitral annular excursion by the distance from the mitral annulus to the LV apex at end-diastole, can be used to assess whole LV systolic performance. The evaluation of LV wall function using this parameter suggests that previous myocardial infarction (MI) causes long-axis myocardial function in remote normal LV walls, as well as in walls with MI, to deteriorate.

The role of apically directed intraventricular isovolumic relaxation flow in speeding early diastolic left ventricular filling.

Left ventricular (LV) systolic performance has been acknowledged to have a close relation to LV early diastolic filling and LV relaxation. However, the mechanism showing how good LV systolic function enhances the LV early diastolic filling has not been fully elucidated from the viewpoint of intraventricular flow dynamics. Thus, we investigated this issue in 82 patients with suggested coronary artery disease who underwent cardiac catheterization. Apically directed intraventricular isovolumic relaxation flow (IRF) and the propagation velocity of early diastolic filling flow were measured using pulsed and color Doppler echocardiography. LV ejection fraction and LV relaxation time constant tau were obtained in cardiac catheterization. As we were not able to measure the IRF velocity less than 14 cm/s that was limited by a Doppler low-cut filter, we analyzed the data collected from 78 patients with measurable IRF velocity. The IRF velocity significantly correlated with LV ejection fraction (r = 0.74, P <.001) and with LV relaxation time constant tau (r = -0.31, P <.01). The propagation velocity of early diastolic filling flow significantly correlated with the IRF velocity (r = 0.73, P <.001) and also significantly correlated with LV ejection fraction (r = 0.70, P <.001). Good LV systolic performance augments LV early diastolic filling directly, mediated by IRF. A faster IRF velocity may play a role in delivering good LV systolic performance to LV early diastolic filling.

Clinical usefulness of carotid arterial wave intensity in assessing left ventricular systolic and early diastolic performance.

Wave intensity (WI) is a novel hemodynamic index, which is defined as (d P/d t) x (d U/d t) at any site of the circulation, where d P/d t and d U/d t are the derivatives of blood pressure and velocity with respect to time, respectively. However, the pathophysiological meanings of this index have not been fully elucidated in the clinical setting. Accordingly, we investigated this issue in 64 patients who underwent invasive evaluation of left ventricular (LV) function. WI was obtained at the right carotid artery using a color Doppler system for blood velocity measurement combined with an echo-tracking method for detecting vessel diameter changes. The vessel diameter changes were automatically converted to pressure waveforms by calibrating its peak and minimum values by systolic and diastolic brachial blood pressures. The WI of the patients showed two sharp positive peaks. The first peak was found at the very early phase of LV ejection, while the second peak was observed near end-ejection. The magnitude of the first peak of WI significantly correlated with the maximum rate of LV pressure rise (LV max. d P/d t) (r = 0.74, P << 0.001). The amplitude of the second peak of WI significantly correlated with the time constant of LV relaxation (r = -0.77, P << 0.001). The amplitude of the second peak was significantly greater in patients with the inertia force of late systolic aortic flow than in those without the inertia force (3,080 +/- 1,741 vs 1,890 +/- 1,291 mmHg m s(-3), P << 0.01). These findings demonstrate that the magnitude of the first peak of WI reflects LV contractile performance, and the amplitude of the second peak of WI is determined by LV behavior during the period from late systole to isovolumic relaxation. WI is a noninvasively obtained, clinically useful parameter for the evaluation of LV systolic and early diastolic performance at the same time.

The mechanism of emergence and clinical significance of apically directed intraventricular flow during isovolumic relaxation.

The mechanism of emergence and the clinical significance of apically directed intraventricular flow during isovolumic relaxation were investigated. The relation between the spatial distribution of the flow and left ventricular (LV) apical wall motion abnormality, as well as LV performance, was studied in 97 patients who underwent cardiac catheterization for evaluation of chest pain. According to the distribution of the flow, the patients were classified into the following 3 groups: flow observed in the whole area between the tip of the papillary muscle and the apex (spread flow) (n = 38), flow observed in the same area that did not fill the whole area (localized flow) (n = 15), and no apparent flow observed in the area (without flow) (n = 44). An absence of flow disclosed apical asynergy with a sensitivity of 97% and specificity of 87%. The time constant of LV relaxation was significantly shorter in patients with spread flow than in those without flow. A significant difference was also observed in end-systolic volume index (18.8 +/- 6.8 vs 30.9 +/- 7.7 vs 42.3 +/- 20.2 mL/m(2), spread flow < localized flow < without flow, P <.05) among the 3 groups. The propagation velocity of LV early diastolic filling flow was significantly greater in patients with spread flow (47.0 +/- 8.3 cm/s) than in those with localized flow (30.7 +/- 7.8 cm/s) or without flow (28.6 +/- 7.8 cm/s) (P <.001). These findings indicate that the greater magnitude of LV elastic recoil and the faster LV relaxation in patients without LV apical asynergy produce apically directed intraventricular flow during isovolumic relaxation, enhancing the speed of LV early diastolic filling. Apically directed intraventricular flow during isovolumic relaxation may play an important role as a mediator of better LV systolic performance and LV relaxation to LV early diastolic filling. Absence of apically directed intraventricular flow during isovolumic relaxation is a manifestation of LV apical asynergy and global LV dysfunction from end systole to early diastole.

Myocardial oxidative metabolism in remote normal regions in the left ventricles with remodeling after myocardial infarction: effect of beta-adrenoceptor blockers.

UNLABELLED: In patients with myocardial infarction (MI), an expansion of the remote normal regions of the left ventricle is often observed. However, the characteristics of such regions are not fully understood. Thus, we investigated this issue from the standpoint of myocardial oxidative metabolism using (11)C-acetate PET. METHODS: In 33 patients with recent MI (24 not receiving beta-blockers, 9 receiving beta-blockers) and 12 age-matched normal control subjects, (11)C-acetate dynamic myocardial PET scanning was performed at rest. Time-activity curves of (11)C-acetate in 5-7 regions of interest (ROIs) on the midventricular transaxial image in each subject were generated, and the clearance rate constant (K(mono)) in each ROI was calculated by monoexponential fitting as an index of myocardial oxidative metabolism. The left ventricular (LV) end-diastolic volume index as an index of LV remodeling and the heart rate. pressure product were obtained in all subjects. RESULTS: The LV end-diastolic volume index was significantly larger in patients with MI without beta-blockers than in normal control subjects (101 +/- 22.5 vs. 61.6 +/- 12.8 mL x m(-2); P < 0.001). There was no significant difference in the heart rate x pressure product between the patients with MI without beta-blockers and the normal control subjects (8,229 +/- 1,503 vs. 8,311 +/- 1,311 mm Hg x min(-1)). The K(mono) in remote normal regions was significantly greater in patients with MI without beta-blockers even when compared with the highest K(mono) on the anteroseptal wall of the left ventricle in normal control subjects (0.078 +/- 0.022 vs. 0.065 +/- 0.007 min(-1); P < 0.01). In contrast, the heart rate. pressure product (6,911 +/- 1,135 mm Hg x min(-1)) and the K(mono) (0.054 +/- 0.009 min(-1)) in remote normal regions were significantly less in patients with beta-blockers than in those without beta-blockers (P < 0.001). No significant difference in the LV end-diastolic volume index was found between the MI patients with and without beta-blockers. Multivariate regression analysis showed that beta-blockers significantly and directly decreased the K(mono) in remote normal regions after adjusting the effect of the heart rate x pressure product, although the prime determinant of the K(mono) in such regions was the heart rate x pressure product. CONCLUSION: Myocardial oxidative metabolism in remote normal regions is accelerated in the left ventricles with remodeling after acute MI. Therapy using beta-blockers normalizes the myocardial oxidative metabolism in such regions through the reduction of the heart rate x pressure product and their direct effect on the myocardium.