Measurement of left ventricular ejection fraction by real time 3D echocardiography in patients with severe systolic dysfunction: comparison with radionuclide angiography.

AIM: Measurement of left ventricular ejection fraction (LVEF) using real time 3D echocardiography (3DE) has been performed in subjects with preserved or modestly reduced systolic function. Our aim was to evaluate this technique in the subset of patients with severe systolic dysfunction. METHODS AND RESULTS: Consecutive patients with LVEF less than 0.35 at two-dimensional echocardiography were included. LVEF obtained by 3DE was compared to the value measured by radionuclide angiography (RNA). Real time full-volume 3DE was performed, with offline semiautomated measurement of LVEF using dedicated software (Cardioview RT, Tomtec) by a single observer blinded to the results of RNA. A total of 50 patients were evaluated, of whom 38 (76%, 27 males, age 69 +/- 13 years) had a 3DE of sufficient quality for analysis. LVEF for this group was 0.21 +/- 0.07 using 3DE and 0.27 +/- 0.08 using RNA. The agreement between the two techniques was rather poor (r = 0.49; P < 0.001; 95% limits of agreements of -0.20 to 0.09). Truncation of the apex was observed in 6 of 38 (16%) patients. CONCLUSION: In patients with severe systolic dysfunction, 3DE shows poor agreement for measurement of LVEF as compared to RNA. There may be underestimation of up to 20% in absolute terms by 3DE. Accordingly, the two methods are not interchangeable for the follow-up of LV function. A limitation of 3DE may, at least in part, be related to the incomplete incorporation of the apical region into the pyramidal image sector in patients with dilated hearts.

Improvement in cardiac sympathetic nerve activity in responders to resynchronization therapy.

AIMS: To assess changes in cardiac adrenergic activity with cardiac resynchronization therapy (CRT), and to investigate whether these changes are related to improvement in left ventricular ejection fraction (LVEF). METHODS AND RESULTS: Sixteen patients (13 males, age 66 +/- 7 years) were studied at baseline and after > or =6 months of CRT (mean follow-up 9.2 +/- 3.2 months). LVEF was assessed by nuclear angiography. Responders were defined as patients showing > or =5% absolute increase in LVEF + improvement in > or =1 NYHA class + absence of heart failure hospitalization. Cardiac sympathetic nerve activity was studied by (123)I-metaiodobenzyl-guanidine ((123)I-MIBG) scintigraphy. Responders (n = 8) showed lower (123)I-MIBG washout at follow-up when compared with non-responders (P = 0.002), indicating lower cardiac sympathetic nerve activity. The decrease in (123)I-MIBG washout at follow-up when compared with baseline was only seen in the responder group (P = 0.036). There was a moderate correlation between increase in LVEF and decrease in (123)I-MIBG washout (r = 0.52, P = 0.04). CONCLUSION: CRT induces a reduction in cardiac sympathetic nerve activity in responders, that parallels an improvement in LVEF, whereas non-responders do not show any significant changes.

The use of perfusion scintigraphy to differentiate proximal right coronary artery stenosis from distal right coronary artery stenosis in patients with inferior left ventricular ischaemia.

OBJECTIVE: The identification of patients with a significant proximal right coronary artery (RCA) is of clinical relevance since it may direct diagnostic and therapeutic strategies. This study was performed to determine parameters of (201)Tl RV perfusion SPECT which can be used to discriminate between proximal and distal RCA stenosis in patients with inferior left ventricular (LV) ischaemia. In addition, feasibility and reproducibility of a new semi-quantitative method for the assessment of RV perfusion were evaluated. METHODS: Inferior LV ischaemia was due to a single distal RCA stenosis in 10 (group I) and proximal RCA stenosis in 27 patients (group II). Twenty patients with normal (201)Tl myocardial perfusion scintigraphy and low likelihood of cardiovascular disease were used as a reference (group III). RESULTS: RV (201)Tl stress uptake did not differ between the three groups. However, group II showed a significantly higher (201)Tl rest uptake indicating RV redistribution whereas in group I and III tracer washout was shown. Extent and severity of LV inferior ischaemia was not different between groups I and II. RV redistribution has a sensitivity of 0.74, a specificity of 0.80, and an overall agreement of 0.76 for detecting proximal RCA stenosis. The feasibility of the assessment of RV (201)Tl perfusion was 94%. Inter-observer and intra-observer coefficients of variation for RV (201)Tl perfusion assessment were 1.5 and 2.4%, respectively. CONCLUSION: RV (201)Tl perfusion scintigraphy is feasible and reproducible. RV (201)Tl redistribution can be used to discriminate between proximal and distal RCA stenosis in patients with inferior LV ischaemia.

Ventricular mechanical dyssynchrony and resynchronization therapy in heart failure: a new indication for Fourier analysis of gated blood-pool radionuclide ventriculography.

In patients with decreased left ventricular ejection fraction and conduction disease, ventricular mechanical dyssynchrony has been demonstrated. To date, resynchronization by biventricular pacing is increasingly used since it improves ventricular function and exercise capacity in patients with heart failure. To optimize and evaluate the effect of resynchronization therapy and to identify patients who may benefit from biventricular pacing the assessment of left ventricular synchronicity is essential. Therefore, a non-invasive and reproducible technique to obtain information on ventricular synchrony is clinically valuable. In this review, the technical background and the role of phase analysis of gated blood-pool nuclear ventriculography in the assessment of ventricular mechanical synchrony, especially in heart failure patients subjected to biventricular pacing, will be discussed.

Optimizing sequential biventricular pacing using radionuclide ventriculography.

BACKGROUND: Biventricular pacemakers are usually programmed with the default setting of synchronous biventricular pacing, although the ventricles may be paced sequentially. Whether this parameter is important for optimizing resynchronization therapy is not clear. OBJECTIVES: The purpose of this study was to investigate whether sequential pacing acutely improves left ventricular ejection fraction (LVEF) and dyssynchrony and to assess the feasibility of nuclear ventriculography for device optimization. METHODS: Twenty-seven patients implanted with a biventricular pacemaker or implantable cardioverter-defibrillator for heart failure were studied. LVEF was measured using planar radionuclide ventriculography during simultaneous biventricular pacing and during sequential pacing at four different interventricular intervals ranging from LV-40 (preexciting the left ventricle by 40 ms) to LV+40 (preexciting the right ventricle). Interventricular and intraventricular dyssynchrony were analyzed by phase analysis at each setting. RESULTS: There was great heterogeneity in individual response to VV interval programming. Twenty-four of 27 patients (89%) had significant changes (both favorable and unfavorable) in LVEF at different interventricular delays, with variations of up to 10% in absolute terms. Simultaneous biventricular pacing yielded maximal LVEF in 9 of 27 patients (33%), with a relative increase in LVEF of 18 +/- 14% by optimized sequential pacing in the remaining patients. Interventricular dyssynchrony varied significantly, with least dyssynchrony at the LV-20 setting (P = .024). There were no significant differences in intraventricular dyssynchrony at the different settings. CONCLUSION: Programming VV intervals has considerable impact on LVEF. However, there is a great degree of variation between patients in response to these settings, requiring individual assessment for device optimization.

Vulnerability of myocardial collateral perfusion: the impact of episodic hypertension.

In patients with coronary artery disease, the presence of left ventricular hypertrophy secondary to hypertension is associated with an increased collateral development. A patient is described who was admitted for myocardial ischemia and severe hypertension. One day after admission, coronary angiography revealed a proximal chronic occlusion of the left anterior descending artery with an extensive collateral vascularization originating from the right and circumflex coronary arteries. In addition, left ventriculography showed antero-apical akinesia that was resolved 5 days later, indicating myocardial stunning. This case illustrates the vulnerability of collateral coronary blood flow to an episode of hypertension, giving rise to myocardial ischemia and even myocardial stunning. This finding advocates aggressive antihypertensive therapy in patients with coronary artery disease and regional myocardial perfusion, which exclusively depends on collateral blood flow.

Comparison between tagged MRI and standard cine MRI for evaluation of left ventricular ejection fraction.

Global left ventricular function is a prognostic indicator and is used to evaluate therapeutical interventions in patients with heart failure. Regional left ventricular function can be determined with tagged MRI. Assessment of global left ventricular function using the tagging data may have additional clinical value without incurring extra scanning time, which is currently a limiting factor in cardiac imaging. Direct determination of end-diastolic volume is not possible with conventional tagged MRI. However, end-systolic volume can be directly measured because myocardium-blood contrast improves through a tagged image series. We investigated the potential of tagged MRI using frequency-domain analysis software to retrospectively track end-diastolic contour from end-systolic contour and subsequently calculate the ejection fraction. Tagged MRI was compared with the standard bright-blood cine MRI in healthy volunteers ( n=20) and patients with previous myocardial infarction ( n=8). Left ventricular ejection fraction derived from tagged MRI is linearly correlated to left ventricular ejection fraction obtained by standard cardiac cine MRI ( y=1.0 x+1.31, r>0.98, p=0.014). In addition, the inter-observer and intra-observer coefficient of variation for left ventricular ejection fraction measurements was low (CV(intra)=0.4%, CV(inter)=1.3%). With tagged MRI, only end-systolic volume needs to be manually determined, and accurate estimation of left ventricular ejection fraction is obtained because end-diastolic and end-systolic volumes are determined using identical anatomical points. Our data indicate that tagged MRI can be used to quantitatively assess both regional and global left ventricular function. Therefore, tagged MRI may be a valuable clinical tool for determining the prognosis and evaluating the effect of therapeutical intervention using a single imaging session in patients with left ventricular dysfunction.

Normal values and within-subject variability of cardiac I-123 MIBG scintigraphy in healthy individuals: implications for clinical studies.

BACKGROUND: Although several myocardial iodine 123 metaiodobenzylguanidine (MIBG) indices are increasingly used to detect alterations in myocardial sympathetic activity in various forms of cardiac pathology, published measurements of normal values and within-subject variability are lacking. METHODS AND RESULTS: Twenty-five healthy volunteers underwent planar and single photon emission computed tomography (SPECT) imaging. Heart-mediastinum ratio (H/M) and myocardial washout were calculated from planar images comparing three different methods for the assessment of myocardial activity: (1) global region over the myocardium (cavity included), (2) global region over the myocardium (cavity excluded), and (3) fixed small myocardial region. Segmental (relative) uptake and washout were assessed by SPECT. For all MIBG indices, the interindividual variation was the lowest for methods 1 and 2. In SPECT this variation was low for relative segmental uptake compared with washout. In 9 subjects a second MIBG scintigraphy was performed after 3 months. The within-subject variability of H/M and washout assessed by planar methods 1 and 2 was 5%, whereas it was approximately 9% for planar method 3. For relative segmental uptake from SPECT, this variability was 5%. CONCLUSION: MIBG H/M (planar) and relative segmental uptake (SPECT) show a low interindividual and within-subject variability. This enables the detection of small (regional) variations in myocardial sympathetic nervous function, especially to monitor the effect of therapeutic interventions in patients with various cardiac diseases.

Site-specific intracoronary delivery of octreotide in humans: a pharmacokinetic study to determine dose-efficacy in restenosis prevention.

Somatostatin analogues have been shown to inhibit smooth muscle cell proliferation after local administration in vivo in animal models and in vitro using human coronary smooth muscle cell cultures. However, the optimal dosage for attaining effective site-specific administration remains undefined. This study was performed to determine the required theoretical dose of the somatostatin analogue, octreotide, to be delivered site specifically, for prevention of restenosis after coronary angioplasty in humans using a previously described methodology to determine regional pharmacokinetics of site-specific intracoronary administrated compounds. In 7 patients, 111In-octreotide, a gamma-labeled somatostatin analogue, was infused post angioplasty at the site of dilatation via a coil-balloon and quantified using a radio-isotopic technique. Efficiency of delivery ranged from 0.1% to 2.7% of the total infused dose of 0.18 microg, corresponding to a mean peak delivered amount of 1.8 +/- 1.9 ng. Total locally bioavailable 111In-octreotide reached 2.28 +/- 2.15 ng h. Based on current in vitro bioavailability and peak concentration data to inhibit proliferation and thymidine incorporation in human coronary smooth muscle cells, a 4000x higher averaged dose (approximately 700 microg) should be infused site specifically to obtain a biologic efficacy in 50% of the treated patients (ED50). Quantification of regional pharmacokinetics enables the determination of a theoretical site-specific dose for achieving appropriate bioavailability above the therapeutic threshold concentration for smooth muscle cell inhibition. This approach is proposed for the determination of the appropriate site-specific coronary infusion dose for the inhibition of restenosis after balloon angioplasty.

Inflow effect in first-pass cardiac and renal MRI.

PURPOSE: To estimate the effect of the inflow effect on the arterial input function in vivo in cardiac and renal MR perfusion imaging using fast gradient echo (GRE) sequences and contrast media. MATERIALS AND METHODS: The MR exam protocol was designed to acquire images at different phases of the cardiac cycle. The arterial input was thus influenced by various blood flow velocities. RESULTS: It was found that the inflow effect was negligible in the left ventricle of the heart, while it was significantly higher in the aorta for the kidney perfusion measurement. This was principally due to the higher through-the-plane component of the blood flow velocity in the aorta than in the left ventricle. CONCLUSION: The inflow effect can be neglected in the heart cavity, but should be taken into account in renal perfusion.

Inorganic species in water and sediments of the Lamone and Marzeno rivers ecosystem.

Analytical results are reported for the determination of inorganic species in water and sediments sampled in the Lamone and Marzeno rivers ecosystem. The species determined are Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, Zn, Hg, F-, Cl- Br-, NO3-, SO4--, Na+, K+, Mg++, Ca++, NH4+ in superficial water, and Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, Zn, Hg in sediments. For all the elements, in addition to detection limits, precision and accuracy are given: the former, expressed as relative standard deviation (s(r)), and the latter, expressed as relative error (e), were good, being in all cases lower than 6%.

Use of high flip angle in T1-prepared FAST sequences for myocardial perfusion quantification.

This study reports on the first use of high flip angle and radio-frequency (RF) spoiling in T1-prepared fast acquisition in steady state (FAST) sequence for myocardial perfusion in patients. T1 dynamic range was measured in vitro with a FAST, an RF FAST and a snapshot fast low-angle shot (FLASH) sequences with a 90 degrees flip angle. Myocardial perfusion was then measured twice in 6 patients during the same MR session. The RF FAST and FLASH, but not the FAST sequence, demonstrated an extended T1 dynamic range; however, the FLASH images were degraded by artifacts not present on the RF FAST images. The myocardial perfusion indices K1 (first-order transfer constant from the blood to the myocardium for the Gd-DTPA) and Vd (distribution volume of Gd-DTPA in myocardium) did not differ significantly between the two injections. K1 was 0.48+/-0.12 ml/min g(-1) and Vd was 12.5+/-2.9%. With an extended T1 dynamic range and the sensitivity required for myocardial perfusion quantification, the RF FAST sequence with a 90 degrees flip angle outperformed the snapshot FLASH sequence in terms of image quality and the FAST sequence in terms of contrast dynamic range.