Usefulness of multidetector computed tomography coronary venous angiography examination before cardiac resynchronization therapy

Purpose  

Cardiac resynchronization therapy (CRT) is a treatment option for selected heart failure patients. In this study, the aim was to evaluate the usefulness of noninvasive cardiac vein imaging using multidetector computed tomography (MDCT) angiography before CRT.     

Effects of left bundle branch block on myocardial FDG PET in patients without significant coronary artery stenoses.

Cardiac PET studies in patients with left bundle branch block (LBBB) are few, and the results are conflicting. In particular, even if a reduced uptake of FDG is reported, confirmation in a large group of patients and exact understanding of the underlying cause are lacking. METHODS: We selected 29 consecutive patients who had complete LBBB and no significant stenosis on coronary angiography scheduled for FDG and 13N-NH3 PET for myocardial viability evaluation at our center. Wall motion was evaluated using 2-dimensional echocardiography. Ten volunteers without coronary stenosis or LBBB served as a control group. RESULTS: All LBBB patients had a reverse mismatch in the septum, defined as reduced uptake of FDG in comparison with 13N-NH3. The mismatch extended to the anterior and inferior walls in 17 patients. The mean (+/-SD) septal-to-lateral ratio was 0.57 +/- 0.11 for FDG (range, 0.28-0.76) and 0.99 +/- 0.12 for 13N-NH3 (range, 0.75-1.18), with P < 0.0001. In contrast, no significant differences in uptake were seen in the control group, which had a septal-to-lateral ratio of 0.95 +/- 0.13 for FDG (range, 0.78-1.15; P < 0.01 with respect to LBBB patients) and 0.94 +/- 0.11 (range, 0.85-1.20) for 13N-NH3. CONCLUSION: Our study suggests that in LBBB patients without significant coronary stenosis, FDG uptake in the septum changes without a correlating change in perfusion. To avoid possible overestimation of necrosis, especially in the LAD territory, this phenomenon must be considered in evaluations of myocardial viability using FDG images.     

Radionuclide imaging of cardiac autonomic innervation

Cardiac autonomic function plays a crucial role in health and disease, with abnormalities both reflecting the severity of the disease and contributing specifically to clinical deterioration and poor prognosis. Radiotracer analogs of the sympathetic mediator norepinephrine have been investigated extensively, and are at the brink of potential widespread clinical use. The most widely studied SPECT tracer, I-123 metaiodobenzylguanidine (¹²³I-mIBG) has consistently shown a strong, independent ability to risk stratify patients with advanced congestive heart failure. Increased global cardiac uptake appears to have a high negative predictive value in terms of cardiac events, especially death and arrhythmias, and therefore and may have a role in guiding therapy, particularly by helping to better select patients unresponsive to conventional medical therapies who would benefit from device therapies such as an ICD (implantable cardioverter defibrillator), CRT (cardiac resynchronization therapy), LVAD (left ventricular assist device), or cardiac transplantation. Cardiac autonomic imaging with SPECT and PET tracers also shows potential to assess patients following cardiac transplant, those with primary arrhythmic condition, coronary artery disease, diabetes mellitus, and during cardiotoxic chemotherapy. Radiotracer imaging of cardiac autonomic function allows visualization and quantitative measurements of underlying molecular aspects of cardiac disease, and should therefore provide a perspective that other cardiac tests cannot.     

Nuclear imaging in cardiac resynchronization therapy.

Recently, cardiac resynchronization therapy (CRT) has become implemented in the treatment of patients with severe heart failure. Although the improvement in systolic function after CRT implantation can be considerable, 20%-30% of patients do not respond to CRT. Evidence is accumulating that the presence of left ventricular (LV) dyssynchrony is mandatory for a response to CRT. Since the early 1980s attempts have been made to assess cardiac dyssynchrony with nuclear imaging, and it has been reported recently that information on LV dyssynchrony can be obtained from gated myocardial perfusion SPECT with phase analysis. Other studies with SPECT have shown that extensive scar tissue will limit the response to CRT; similarly, it has been demonstrated that viable tissue (assessed with SPECT) in the target zone for the LV pacing lead (usually the lateral wall) is needed for a response to CRT. Moreover, studies with PET have provided insight into the changes in myocardial perfusion, metabolism, and efficiency after CRT. In the current review, a comprehensive summary is provided on the potential role of nuclear imaging in the selection of heart failure patients for CRT. The value of other imaging techniques is also addressed.     

Cardiac motion analysis to improve pacing site selection in CRT

RATIONALE AND OBJECTIVES: The aim of the study is to build cardiac wall motion models to characterize mechanical dyssynchrony and predict pacing sites for the left ventricle of the heart in cardiac resynchronization therapy (CRT). MATERIALS AND METHODS: Cardiac magnetic resonance imaging data from 20 patients are used, in which half have heart failure problems. We propose two spatio-temporal ventricular motion models to analyze the mechanical dyssynchrony of heart: radial motion series and wall motion series (a time series of radial length or wall thickness change). The hierarchical agglomerative clustering technique is applied to the motion series to find candidate pacing sites. All experiments are performed separately on each ventricular motion model to facilitate performance comparison among models. RESULTS: The experimental results demonstrate that the proposed methods perform as well as we expect. Our techniques not only effectively generate the candidate pacing sites list that can help guide CRT, but also derive clustering results that can distinguish the heart conditions between patients and normals perfectly to help medical diagnosis and prognosis. After comparing the results between two different ventricular motion models, the wall motion series model shows a better performance. CONCLUSION: In a traditional CRT device deployment, pacing sites are selected without efficient prediction, which runs the risk of suboptimal benefits. Our techniques can extract useful wall motion information from ventricular mechanical dyssynchrony and identify the candidate pacing sites with maximum contraction delay to assist pacemaker implantation in CRT.     

Cardiac neuronal imaging: Application in the evaluation of cardiac disease

Conclusion  The sympathetic nervous system plays an important role in cardiovascular physiology. Both SPECT with MIBG and PET can be used to visualize the sympathetic innervation of the heart and the abnormalities in innervation caused by, for example, ischemia, heart failure, and arrhythmogenic disorders. Furthermore, cardiac neuronal imaging allows early detection of autonomic neuropathy in diabetes mellitus. Although SPECT imaging is widely available and technically less demanding than PET, the latter has important advantages. PET can be used to achieve high spatial and temporal resolution, as well as absolute quantification, in a noninvasive manner. It also can provide a wide range of different radiolabeled catecholamines, catecholamine analogs, and receptor ligands. It should be noted, however, that most experience has been obtained with SPECT and MIBG. Assessment of sympathetic nerve activity in patients with heart failure has been shown to provide important prognostic information, and cardiac neuronal imaging can potentially identify patients who are at increased risk of sudden death. Moreover, therapeutic effects of different treatment strategies can be evaluated by MIBG SPECT as well as by PET imaging. To establish the clinical utility of cardiac neuronal imaging, it will be necessary to determine the incremental value of innervation imaging to triage heart failure patients to medical therapy, CRT (with or without ICD), or heart transplantation.     

Noninvasive estimation of regional myocardial oxygen consumption by positron emission tomography with carbon-11 acetate in patients with myocardial infarction

We previously demonstrated in experimental studies that myocardial oxygen consumption (MVO2) can be estimated noninvasively with positron emission tomography (PET) from analysis of the myocardial turnover rate constant (k) after administration of carbon-11 (11C) acetate. To determine regional k in healthy human subjects and to estimate alterations in MVO2 accompanying myocardial ischemia, we administered [11C]acetate to five healthy human volunteers and to six patients with myocardial infarction. Extraction of [11C]acetate by the myocardium was avid and clearance from the blood-pool rapid yielding myocardial images of excellent quality. Regional k was homogeneous in myocardium of healthy volunteers (coefficient variation = 11%). In patients, k in regions remote from the area of infarction was not different from values in myocardium of healthy human volunteers (0.061 +/- 0.025 compared with 0.057 +/- 0.008 min-1). In contrast, MVO2 in the center of the infarct region was only 6% of that in remote regions (p less than 0.01). In four patients studied within 48 hr of infarction and again more than seven days after the acute event, regional k and MVO2 did not change. The approach developed should facilitate evaluation of the efficacy of interventions designed to enhance recovery of jeopardized myocardium and permit estimation of regional MVO2 and metabolic reserve underlying cardiac disease of diverse etiologies.     

Impact of cardiac reverse remodeling after cardiac resynchronization therapy assessed by myocardial perfusion imaging on ventricular arrhythmia

Journal of Nuclear Cardiology - Although cardiac resynchronization therapy (CRT) has been a useful treatment of heart failure, patients with CRT are still in risk of sudden cardiac death due to...     

Alterations of the sympathetic nervous system and metabolic performance of the cardiomyopathic heart

Little is known about the effects of altered sympathetic innervation on the efficiency of the cardiomyopathic heart. Thus, it was the aim of this study to determine non-invasively the relationship between the metabolic cost of cardiac work and alterations of the sympathetic nervous system. In ten patients with chronic idiopathic dilated cardiomyopathy, left ventricular function and geometry were assessed by tomographic radionuclide angiography. Myocardial oxidative metabolism was quantified by the clearance constant k(mono) for carbon-11 acetate, determined by positron emission tomography (PET). Cardiac efficiency was then estimated by the work-metabolic index [WMI = stroke volume index x heart rate x systolic pressure/k(mono)]. Additionally, myocardial presynaptic sympathetic innervation was investigated in the same PET session using 11C-hydroxyephedrine, and plasma norepinephrine levels were determined by high-performance liquid chromatography. The WMI was 3.0+/-1.3 mmHg x ml x 10(6)/m2 and correlated significantly with left ventricular ejection fraction (19%+/-10%; r=0.66, P<0.04) and peripheral vascular resistance (3,638+/-1,085 dynes x s/cm5; r=-0.75, P<0.01). Cardiac hydroxyephedrine retention, reflecting integrity of presynaptic innervation, was abnormally low in 58%+/-38% of the left ventricle. Cardiac hydroxyephedrine retention (r=0.65, P<0.05) and plasma norepinephrine concentration (r=-0.80, P<0.01) both correlated significantly with the WMI. At multivariate stepwise linear regression, only plasma norepinephrine and peripheral vascular resistance were independent determinants of the WMI. In conclusion, metabolic performance of the cardiomyopathic heart decreases with increasing alterations of the sympathetic nervous system. Increasing afterload and effects of systemic sympathetic activation, however, seem to play a dominant role while direct alterations of cardiac presynaptic sympathetic innervation are not independently associated.     

Simultaneous cardiac output and regional myocardial perfusion determination with PET and nitrogen 13 ammonia

BACKGROUND: The purpose of this study was to evaluate the possibility of measuring cardiac output during positron emission tomography (PET) examination of myocardial perfusion with nitrogen 13 ammonia. METHODS AND RESULTS: In 7 patients undergoing right-sided cardiac catheterization for evaluation of heart failure and 6 patients who had undergone heart transplantation, a thermodilution catheter for continuous measurement of cardiac output was inserted. An N-13 ammonia scan of the heart was subsequently performed, and with use of factor analysis, the time-activity curve from the right ventricle was derived from the dynamic image sequence. The PET-derived cardiac output was subsequently obtained according to the Stewart-Hamilton principle as the amount of injected tracer divided by the area under the time-activity curve. PET-acquired cardiac output measurements correlated closely with the invasively determined values for a wide range of cardiac output values (P < .0001). The mean difference was 0.12 L/min, with an SD of 0.74 L/min. The interobserver variation was low, with a mean difference of 0.06 L/min and an SD of 0.46 L/min. CONCLUSIONS: Cardiac output determination with N-13 ammonia and PET appears to be both accurate and precise and can be performed simultaneously with measurement of myocardial perfusion.     

The effect of device-based cardiac contractility modulation therapy on myocardial efficiency and oxidative metabolism in patients with heart failure

Purpose  

Cardiac contractility modulation (CCM) is a device-based therapy that involves delivery of nonexcitatory electrical signals resulting in improved ventricular function and a reversal of maladaptive cardiac fetal gene programmes. Our aim was to evaluate whether acute application of CCM leads to an increase in myocardial oxygen consumption (MVO₂) in patients with chronic heart failure using ¹¹C-acetate positron emission tomography (PET).     

Validity of estimates of myocardial oxidative metabolism with carbon-11 acetate and positron emission tomography despite altered patterns of substrate utilization

We recently demonstrated that the myocardial turnover rate constant (k) measured noninvasively with positron emission tomography (PET) after intravenous administration of [11C]acetate provides a reliable index of myocardial oxidative metabolism (MVO2) theoretically independent of the pattern of myocardial substrate use. However, because estimates of metabolism with other metabolic tracers are sensitive to substrate use, we measured k in 12 dogs during baseline conditions and again after infusion of either glucose (n = 8) or Intralipid (n = 4), interventions that raised arterial glucose or fatty acids by more than fivefold with concomitant changes in myocardial substrate use. Following glucose administration k increased, but no difference was detected after compensation for changes in hemodynamics and myocardial work induced by the infusion (0.18 +/- 0.03 min-1 (t1/2 = 3.9 min) at baseline compared with 0.22 +/- 0.06 min-1 (t1/2 = 3.2 min, p = N.S.). k was not affected by Intralipid infusion (k = 0.15 +/- 0.06 min-1 at baseline and 0.14 +/- 0.04 min-1 during infusion), and correlated closely with MVO2 measured directly (n = 19 comparisons, r = 0.89). The results indicate that estimates of MVO2 using [11C]acetate and PET are valid despite changes in the pattern of myocardial substrate utilization.     

Assessment of left ventricular mechanical dyssynchrony by phase analysis of ECG-gated SPECT myocardial perfusion imaging

Cardiac resynchronization therapy (CRT) has shown benefits in patients with severe heart failure. However, at least 30% of patients selected for CRT by use of traditional criteria (New York Heart Association class III or IV, depressed left ventricular [LV] ejection fraction, and prolonged QRS duration) do not respond to CRT. Recent studies with tissue Doppler imaging have shown that the presence of LV dyssynchrony is an important predictor of response to CRT. Phase analysis has been developed to allow assessment of LV dyssynchrony by gated single photon emission computed tomography myocardial perfusion imaging. This technique uses Fourier harmonic functions to approximate regional wall thickness changes over the cardiac cycle and to calculate the regional onset-of-mechanical contraction phase. Once the onset-of-mechanical contraction phases are obtained 3-dimensionally over the left ventricle, a phase distribution map is formed that represents the degree of LV dyssynchrony. This technique has been compared with other methods of measuring LV dyssynchrony and shown promising results in clinical evaluations. In this review the phase analysis methodology is described, and its up-to-date validations are summarized.     

Identification of cardiac sarcoidosis with (13)N-NH(3)/(18)F-FDG PET.

To our knowledge, no study investigating the usefulness of cardiac PET for detection of myocardial involvement of sarcoidosis is available. We investigated whether (13)N-NH(3)/(18)F-FDG PET could identify cardiac involvement in patients with sarcoidosis. METHODS: Seventeen patients with cardiac sarcoidosis underwent cardiac (13)N-NH(3)/(18)F-FDG PET under fasting condition. Systemic sarcoidosis was diagnosed by histologically proven noncaseating epithelioid granuloma, and cardiac sarcoidosis was diagnosed according to the Japanese Ministry of Health and Welfare guidelines for diagnosing cardiac sarcoidosis. RESULTS: Only 6 patients exhibited myocardial (201)Tl defects and only 3 patients exhibited abnormal (67)Ga accumulation in the heart. Thirteen patients exhibited (13)N-NH(3) defects, and 14 patients exhibited increased (18)F-FDG uptake in the heart; 12 patients exhibited both (13)N-NH(3) defects and increased (18)F-FDG uptake, 2 patients exhibited increased (18)F-FDG uptake but no (13)N-NH(3) defect, and 1 patient exhibited (13)N-NH(3) defects but no increased (18)F-FDG uptake. (13)N-NH(3) defects were observed frequently in the basal anteroseptal wall of the left ventricle, and increased (18)F-FDG uptake was observed frequently in the basal and midanteroseptal-lateral wall of the left ventricle. Involvement of the apex was rare. Seven patients were treated with steroid hormone and underwent follow-up cardiac PET 1 mo after steroid therapy. (13)N-NH(3) defects exhibited no significant change after steroid therapy, whereas increased (18)F-FDG uptake was markedly diminished in size and intensity in 5 patients and disappeared completely in 2 patients. CONCLUSION: Our findings suggest that cardiac (13)N-NH(3)/(18)F-FDG PET is the most useful method both for the identification of cardiac involvement of sarcoidosis and for the assessment of cardiac sarcoidosis disease activity.     

Quantitative comparison of 2D and 3D circumferential strain using MRI tagging in normal and LBBB hearts.

The response to cardiac resynchronization therapy (CRT), which is applied to patients with heart failure (HF) and left bundle-branch block (LBBB), can be predicted from the mechanical dyssynchrony measured on circumferential strain. Circumferential strain can be assessed by either 2D or 3D strain analysis. In this study was evaluated the difference between 2D and 3D circumferential strain using MR tagging with high temporal resolution (14 ms). Six healthy volunteers and five patients with LBBB were evaluated. We compared the 2D and 3D circumferential strains by computing the mechanical dyssynchrony and the cross correlation (r) between 2D and 3D strain curves, and by quantifying the differences in peak circumferential shortening, time to onset, and time to peak of shortening. The obtained maximum r(2) values were 0.97 +/- 0.03 and 0.87 +/- 0.16 for the healthy and LBBB populations, respectively, and thus showed a good similarity between 2D and 3D strain curves. No significant difference was observed between 2D and 3D in time to onset, time to peak, or peak circumferential shortening. Thus, to measure dyssynchrony, 2D strain analysis will suffice. Since 2D analysis is easier to implement than 3D analysis, this finding brings the application of MRI tagging and strain analysis closer to the clinical routine.     

Extent of viability to predict response to cardiac resynchronization therapy in ischemic heart failure patients.

The response to cardiac resynchronization therapy (CRT) varies significantly among individuals. Preliminary data suggest that the presence of myocardial viability may be important for response to CRT. The aim of this study was to evaluate whether the extent of viability could predict response to CRT after 6 mo. METHODS: Sixty-one consecutive patients with advanced heart failure, left ventricular ejection fraction < 35%, QRS duration > 120 ms, and chronic coronary artery disease were included. To determine the extent of viability all patients underwent nuclear imaging with 18F-FDG SPECT before implantation. Clinical and echocardiographic parameters were assessed at baseline and after 6 mo of follow-up. RESULTS: The presence of myocardial viability was directly related to an increase in left ventricular ejection fraction after 6 mo of CRT. Furthermore, the extent of viability in responders (n = 38) was significantly larger compared with that of nonresponders (n = 23; 12 +/- 3 vs. 7 +/- 3 viable segments, P < 0.01). Moreover, the optimal cutoff value to predict clinical response to CRT was identified at an extent of 11 viable segments or more (in a 17-segment model), yielding a sensitivity of 74% and a specificity of 87%. CONCLUSION: The presence of myocardial viability is directly related to response to CRT in patients with ischemic heart failure. Interestingly, using a cutoff level of 11 viable segments or more, the extent of viability could be used to predict response. Therefore, evaluation for myocardial viability may be considered in the selection process for CRT.     

Cardiac neurotransmission imaging.

Cardiac neurotransmission imaging with SPECT and PET allows in vivo assessment of presynaptic reuptake and neurotransmitter storage as well as of regional distribution and activity of postsynaptic receptors. In this way, the biochemical processes that occur during neurotransmission can be investigated in vivo at a micromolar level using radiolabeled neurotransmitters and receptor ligands. SPECT and PET of cardiac neurotransmission characterize myocardial neuronal function in primary cardioneuropathies, in which the heart has no significant structural abnormality, and in secondary cardioneuropathies caused by the metabolic and functional changes that take place in different diseases of the heart. In patients with heart failure, the assessment of sympathetic activity has important prognostic implications and will result in better therapy and outcome. In diabetic patients, scintigraphic techniques allow the detection of autonomic neuropathy in early stages of the disease. In conditions with a risk of sudden death, such as idiopathic ventricular tachycardia and arrhythmogenic right ventricular cardiomyopathy, PET and SPECT reveal altered neuronal function when no other structural abnormality is seen. In patients with ischemic heart disease, heart transplantation, drug-induced cardiotoxicity, and dysautonomias, assessment of neuronal function can help characterize the disease and improve prognostic stratification. Future directions include the development of tracers for new types of receptors, the targeting of second messenger molecules, and the early assessment of cardiac neurotransmission in genetically predisposed subjects for prevention and early treatment of heart failure.     

PET/CT quantitation of the effect of patient-related factors on cardiac 18F-FDG uptake.

The effect of multiple patient-related factors on the degree of cardiac 18F-FDG uptake was assessed. METHODS: Five hundred four consecutive patients undergoing routine 18F-FDG PET/CT studies completed a clinical questionnaire. 18F-FDG uptake was measured as the mean standardized uptake value within the heart delineated on the CT component of the study. Univariate and multivariate analyses assessed the influence of 51 clinical factors on cardiac 18F-FDG uptake. RESULTS: On both multivariate and univariate analyses, cardiac 18F-FDG uptake was significantly lower in diabetics and in patients receiving bezafibrate or levothyroxine. Cardiac 18F-FDG uptake was significantly higher in men, patients younger than 30 y old, fasting duration of <5 h, patients with heart failure, and those receiving benzodiazepines. CONCLUSION: Cardiac 18F-FDG uptake was lower in patients receiving bezafibrate and levothyroxine and higher in patients receiving benzodiazepines. If further confirmed by prospectively designed studies, manipulation of these drugs may represent tools for optimized PET/CT imaging.     

Cardiac pacemakers and central venous lines can induce focal artifacts on CT-corrected PET images.

PET/CT imaging can be associated with focal artifactual (18)F-FDG uptake introduced by metallic implants or contrast agents. It is unknown whether cardiac pacemakers or permanent central venous catheters can also result in such artifacts. METHODS: Twenty-seven patients with permanent central venous lines (13 men and 14 women; mean age +/- SD, 53.8 +/- 16.2 y) and 9 patients with pacemakers (7 men and 2 women; mean age +/- SD, 74.8 +/- 5.1 y) who were referred for a variety of oncologic indications were studied with lutetium-oxyorthosilicate-based dual-slice PET/CT after injection of 7.77 MBq/kg of (18)F-FDG. CT-corrected and -uncorrected PET images were reviewed, and (18)F-FDG uptake was graded as absent, mild, moderate, or intense. RESULTS: CT-corrected PET images revealed focally increased uptake of moderate intensity in all patients with cardiac pacemakers and focally increased uptake of mild intensity in 8 of 27 patients (29.6%) with central venous lines. CONCLUSION: Cardiac pacemakers and reservoirs of central venous lines can induce artifactual (18)F-FDG on CT-corrected PET images. Thus, in patients with permanent central lines or pacemakers, both corrected and uncorrected PET images need to be reviewed to avoid false-positive PET findings.     

18-Fluorodeoxyglucose imaging with positron emission tomography and single photon emission computed tomography: cardiac applications

The assessment of myocardial viability has become an important aspect of the diagnostic and prognostic work-up of patients with ischemic cardiomyopathy. Although revascularization may be considered in patients with extensive viable myocardium, patients with predominantly scar tissue should be treated medically or evaluated for heart transplantation. Among the many viability tests, noninvasive assessment of cardiac glucose use (as a marker of viable tissue) with F18-fluorodeoxyglucose (FDG) is considered the most accurate technique to detect viable myocardium. Cardiac FDG uptake has traditionally been imaged with positron emission tomography (PET). Clinical studies have shown that FDG-PET can accurately identify patients with viable myocardium that are likely to benefit from revascularization procedures, in terms of improvement of left ventricular (LV) function, alleviation of heart failure symptoms, and improvement of long-term prognosis. However, the restricted availability of PET equipment cannot meet the increasing demand for viability studies. As a consequence, much effort has been invested over the past years in the development of 511-keV collimators, enabling FDG imaging with single-photon emission computed tomography (SPECT). Because SPECT cameras are widely available, this approach may allow a more widespread use of FDG for the assessment of myocardial viability. Initial studies have directly compared FDG-SPECT with FDG-PET and consistently reported a good agreement for the assessment of myocardial viability between these 2 techniques. Additional studies have shown that FDG-SPECT can also predict improvement of LV function and heart failure symptoms after revascularization. Finally, recent developments, including coincidence imaging and attenuation correction, may further optimize cardiac FDG imaging (for the assessment of viability) without PET systems.