Cardiac adrenergic innervation within the first 3 months after acute myocardial infarction

It is widely accepted that myocardial infarction results in adrenergic denervation of the infarcted and peri‐infarcted myocardium. On the contrary, the concept of re‐innervation of adrenergic nerve fibres is less well established. Although there is evidence of partial re‐innervation occuring several months after myocardial infarction, the extent and time scale of re‐innervation are only poorly known. In this study we investigated changes in cardiac adrenergic innervation and myocardial perfusion during the early convalescence period (the first 3 months) after an acute myocardial infarction. Single‐photon emission computed tomographic imaging was conducted in 15 men 1 week and 3 months after an acute myocardial infarction with I¹²³‐metaiodobentzylguanidine (MIBG) and Tc^99m‐sestamibi (MIBI) to determine the extent of adrenergic denervation and impaired perfusion, respectively. A MIBG and MIBI defect was determined as regional uptake ≤30% of maximal myocardial activity. The size of the MIBG defect calculated as a percentage of left ventricular mass remained unchanged between 1 week and 3 months after myocardial infarction (31·1 ± 17·3% vs. 30·5 ± 16·8%, respectively). Accordingly, MIBG activity of the infarct and peri‐infarct zones (expressed as a percentage of MIBG activity of the myocardium with normal perfusion) showed no significant change (23·7 ± 10·0% vs. 25·3 ± 11·0% and 39·0 ± 11·3% vs. 40·8 ± 12·8%, respectively) during the follow‐up. On the other hand, the size of MIBI defect decreased significantly during the follow‐up (14·2 ± 11·5% vs. 11·4 ± 9·7%, P<0·05, respectively) indicating improved myocardial perfusion. The results demonstrate that cardiac adrenergic re‐innervation is a slow process; despite a significant increase in myocardial perfusion we found no evidence of adrenergic re‐innervation during the first 3 months after acute myocardial infarction.     

Body mass index and rest myocardial perfusion defect predicts cardiac death in patients with chronic heart failure

Gated single photon emission computed tomography (SPECT) myocardial perfusion imaging has proven to be invaluable not only in assessing myocardial perfusion, but also in providing functional and volumetric information. The aim of this study was to investigate the value of clinical variables and rest gated SPECT myocardial perfusion imaging for predicting cardiac death in patients with chronic heart failure (CHF). Seventy-three consecutive hospitalized patients with CHF (aged 50.7 ± 16.5 years, 60 men and 13 women; 25 ischemic CHF and 48 non-ischemic CHF) and left ventricular ejection fraction on echocardiography <40%, who underwent rest gated SPECT myocardial perfusion imaging, were followed up for this study. Univariate and multivariate analysis of clinical characteristics and gated SPECT parameters for prediction of cardiac death were performed. During the follow-up period (18.6 ± 8.5 months), 14 (19.2%) cardiac deaths occurred. Multivariate Cox analysis showed that body mass index (BMI, 23.3 ± 4.1 kg/m², hazard ratio = 0.85, P = 0.025) and summed rest score (SRS, 11.8 ± 11.5, hazard ratio = 1.05, P = 0.021) were predictive for cardiac death. The optimal threshold of BMI was 25 kg/m² and patients with BMI < 25 kg/m² had lower survival rate (P = 0.013). The optimal threshold of SRS was set as 11 and patients with SRS > 11 had lower survival rate (P = 0.009). Rest gated SPECT myocardial perfusion imaging provides prognostic information in patients with CHF. BMI and SRS are both predictors of cardiac death in patients with CHF.     

Regional Cardiac Sympathetic Nervous System Evaluation Using 123I-mIBG SPECT in Patients with Heart Failure

BackgroundHeart failure (HF) involves both mechanical and autonomic nervous system dysfunction that can lead to sudden cardiac death. In the failing human heart, there is increased release of norepinephrine from neurons and reduced uptake. Iodine-123–labeled metaiodobenzylguanidine (123I-mIBG) demonstrates reduced global uptake and increased washout associated with increased mortality in HF. This research examined the potential benefits of single-photon emission computed tomography (SPECT) regional quantitation in risk stratification of HF patients and its role in prediction of cardiac morbidity and mortality.MethodsTwenty-two clinically diagnosed HF patients were recruited into this study. The subjects underwent myocardial perfusion SPECT and cardiac sympathetic imaging with 123I-mIBG. Early (at 15 min after injection) and delayed (four hours after injection) planar and SPECT were performed. Visual and semiquantitative analysis was conducted, and global (from planar imaging) and regional (from SPECT imaging) uptake and washout indices determined. The patients were clinically followed for up to two years, and the cardiac events (CEs) in these patients were recorded and correlated with the various parameters.ResultsThe occurrence of a CE in HF was independent of the patients' demographics or the cause of HF. Genetic biomarkers were unable to reliably predict CEs. Global or regional uptake had limited ability to predict a CE, whereas regional washout from the inferior wall (P = .005) was a statistically significant predictor of CEs. Similarly, a high washout of 40% or more from the peri-infarcted and noninfarcted segments on myocardial perfusion scintigraphy was also a significant predictor of CEs (P = .035).ConclusionHF is a complex, multifactorial, progressive disease that appears to begin regionally. 123I-mIBG provides a valuable tool in imaging the global and regional sympathetic nervous system innervation of the heart. This may allow early identification and stratification of patients at risk of sudden cardiac death.     

Cardiac sympathetic activity is associated with inflammation and neurohumoral activation in patients with idiopathic dilated cardiomyopathy

Background: Idiopathic dilated cardiomyopathy (IDC) is characterized by sympathetic nervous overactivity, inflammation and neurohumoral activation; however, their interrelationships are poorly understood. Methods and results: We studied 99 patients with IDC (age 54 ± 1 years, left ventricular ejection fraction (EF) 40 ± 1%, maximum oxygen uptake (VO₂max) 20 ± 1 ml kg^?1 min^?2, mean ± SEM) by using ¹²³I‐metaiodobenzylguanidine (MIBG) imaging. MIBG washout and MIBG heart/mediastinum (H/M)‐ratio at 4 h postinjection were calculated. In addition, the plasma levels of interleukin (IL)‐6 and N‐terminal B‐type natriuretic peptide (NT‐proBNP) were measured. MIBG washout and MIBG H/M ratio had a significant correlation with IL‐6 (r = 0·42, P<0·001 and r = ?0·31, P<0·01) and NT‐proBNP (r = 0·48, P<0·001 and r = ?0·40, P<0·001). During a median follow‐up of 4·1 years, 20 patients (20%) had an adverse cardiac event (death, heart transplantation or application of biventricular pacemaker or implantable cardioverter–defibrillator). In these patients, MIBG washout was higher (53 ± 4 versus 40 ± 2%, P = 0·01) and H/M ratio lower (1·38 ± 0·04 versus 1·51 ± 0·02, P = 0·01) than in patients without an event. Conclusions: In dilated cardiomyopathy, myocardial sympathetic innervation and activity are related to inflammation and neurohumoral activation. These relationships are at least partly independent of left ventricular function and exercise capacity.     

Iodine 123-metaiodobenzylguanidine imaging reflect generalized sympathetic activation in patients with left ventricular dysfunction

BACKGROUND: Iodine 123-metaiodobenzylguanidine (MIBG) imaging has been used to assess cardiac sympathetic nerve abnormalities. To determine the role of MIBG imaging as a measure of generalized sympathetic nerve activity, MIBG imaging was evaluated with muscle sympathetic nerve activity (MSNA) and plasma norepinephrine (noradrenaline) level in patients with old myocardial infarction. METHODS: Myocardial MIBG scintigraphy, MSNA and plasma norepinephrine measurement were performed within 3 days in 35 patients with old myocardial infarction. Patients were divided into three groups according to their ejection fraction (EF); preserved (EF > or = 50%, 12 patients), intermediate (35% < EF < 50%, 13 patients), or depressed (EF < or = 35%, 10 patients).The heart to mediastinum (H/M) ratio was obtained 4 h after tracer injection from the chest anterior view image. MIBG washout rate was calculated from the early and delayed images. MSNA was recorded by microneurography. RESULTS: Plasma norepinephrine level had weak negative correlations with early H/M ratio (r = 0.37, P<0.05) and delayed H/M ratio (r = 0.33, P<0.05), and a positive correlation with MIBG washout rate (r = 0.54, P<0.01). MSNA had weak negative correlations with early H/M ratio (r = 0.51, P<0.05) and delayed H/M ratio (r = 0.52, P<0.05). However, a strong correlation was found between MSNA and MIBG washout rate (r = 0.88, P<0.001). Despite no significant differences in plasma norepinephrine level and H/M ratio, patients with intermediate and depressed EF had higher MIBG washout rate and MSNA compared with those with preserved EF. CONCLUSIONS: Increased in cardiac sympathetic nerve activity was associated with augmented sympathetic outflow of the skeletal muscle and hence, MIBG washout rate allow the assessment of general sympathetic nerve activity.     

Use of metaiodobenzylguanidine for assessing status of ends of myocardial sympathetic nerves in myocardium of patients with bronchial asthma

AIM: To evaluate sympathetic nervous system activity of the heart in patients with bronchial asthma (BA) given beta-adrenomimetics (BAM). MATERIAL AND METHODS: 27 patients with moderate BA (13 patients in an acute phase and 14 patients in remission) treated with BAM and 13 healthy people were examined by using 123I-metaiodobenzylguanidine (MIBG) myocardial planar scintigraphy and estimating the washout rate, early (15-min) and late (240-min) uptake; single-photon emission computed tomography; assessment of MIBG distribution in the left ventricular myocardium, catecholamine excretion with urine. RESULTS: It was found that the MIBG washout rate was significantly higher in asthmatic patients especially in the acute period. The cardiac MIBG uptake was significantly lower in the group of patients with impaired cardiac sympathetic activity. More inhomogeneous myocardial MIBG uptake also occurred in the asthmatic group. Norepinephrine and epinephrine excretion was significantly higher in patients with bronchial asthma and cathecholamine and MIBG excretions correlated. CONCLUSION: Cardiac functional sympathetic activity impairment in asthmatic patients was shown by increased MIBG washout rate and reduced myocardial MIBG uptake, more inhomogeneous substance distribution in the left ventricular myocardium and higher catecholamine excretion levels reflecting sympathetic nervous activity intensification.     

Normal range and regional heterogeneity of myocardial perfusion in healthy human myocardium: assessment on dynamic perfusion CT using 128-slice dual-source CT

Information about myocardial perfusion in healthy hearts is essential for evaluating patients with ischemic heart disease. The purpose of this study was to determine the range and regional variability of myocardial perfusion in normal volunteers on dynamic perfusion computed tomography (CT). Myocardial perfusion was assessed in 19 healthy volunteers (age 33–60 years; 11 men) at rest and during adenosine-induced hyperemia using a 128-slice dual-source CT scanner. Data were quantified as cc/cc/min for the transmural myocardium based on a 17-segment American Heart Association model. Mean myocardial blood flows (MBF) were 1.73 ± 0.33 cc/cc/min during adenosine-induced hyperemia, 0.83 ± 0.21 cc/cc/min at rest, and perfusion reserve was 2.20 ± 0.53. Regional variability was 17 ± 5 % for hyperemic perfusion, 18 ± 7 % for resting, and 21 ± 6 % for perfusion reserve. Although statistically insignificant, perfusion in the septum was lower at rest and during hyperemia than in other regions. Women tended to have lower perfusion during hyperemia (1.65 ± 0.40 vs. 1.79 ± 0.28 cc/cc/min, P = 0.40), and higher perfusion at rest than men (0.91 ± 0.27 vs. 0.77 ± 0.15 cc/cc/min, P = 0.23), resulting in lower perfusion reserve (1.86 ± 0.31 vs. 2.45 ± 0.53, P = 0.11). This small cohort of healthy volunteers study reveals normal myocardial perfusion parameter on dynamic perfusion CT as follows: mean MBF is 1.73 ± 0.33 cc/cc/min during hyperemia, 0.83 ± 0.21 cc/cc/min at rest, and perfusion reserve is 2.20 ± 0.53. And the study also demonstrates considerable regional heterogeneity of the myocardial perfusion.     

Myocardial perfusion MRI shows impaired perfusion of the mouse hypertrophic left ventricle

There is growing consensus that myocardial perfusion deficits play a pivotal role in the transition from compensated to overt decompensated hypertrophy. The purpose of this study was to systematically study myocardial perfusion deficits in the highly relevant model of pressure overload induced hypertrophy and heart failure by transverse aortic constriction (TAC), which was not done thus far. Regional left ventricular (LV) myocardial perfusion (mL/min/g) was assessed in healthy mice (n = 6) and mice with TAC (n = 14). A dual-bolus first-pass perfusion MRI technique was employed to longitudinally quantify myocardial perfusion values between 1 and 10 weeks after surgery. LV function and morphology were quantified from cinematographic MRI. Myocardial rest perfusion values in both groups did not change significantly over time, in line with the essentially constant global LV function and mass. Myocardial perfusion was significantly decreased in TAC mice (4.2 ± 0.9 mL/min/g) in comparison to controls (7.6 ± 1.8 mL/min/g) (P = 0.001). No regional differences in perfusion were observed within the LV wall. Importantly, increased LV volumes and mass, and decreased ejection fraction correlated with decreased myocardial perfusion (P < 0.001, in all cases). Total LV blood flow was decreased in TAC mice (0.5 ± 0.1 mL/min, P < 0.001) in comparison to control mice (0.7 ± 0.2 mL/min). Myocardial perfusion in TAC mice was significantly reduced as compared to healthy controls. Perfusion was proportional to LV volume and mass, and related to decreased LV ejection fraction. Furthermore, this study demonstrates the potential of quantitative first-pass contrast-enhanced MRI for the study of perfusion deficits in the diseased mouse heart.     

Mapping contrast agent uptake and retention in MRI studies of myocardial perfusion: case control study of dogs with Duchenne muscular dystrophy

Myocardial perfusion studies using dynamic contrast-enhanced cardiac magnetic resonance imaging (CMRI) could provide valuable, quantitative information regarding heart physiology in diseases such as Duchenne muscular dystrophy (DMD), that lead to diffuse myocardial damage. The goal of this effort was to develop an intuitive but physiologically meaningful method for quantifying myocardial perfusion by CMRI and to test its ability to detect global myocardial differences in a dog model of DMD. A discrete-time model was developed that parameterizes contrast agent kinetics in terms of an uptake coefficient that describes the forward flux of contrast agent into the tissue, and a retention coefficient that describes the rate of decay in tissue concentration due to contrast agent efflux. This model was tested in 5 dogs with DMD and 6 healthy controls which were imaged using a perfusion sequence on a 3T clinical scanner. CINE and delayed-enhancement CMRI acquisitions were also used to assess cardiac function and the presence of myocardial scar. Among functional parameters measured by CMRI, no significant differences were observed. No myocardial scar was observed. Increased perfusion in DMD was observed with an uptake coefficient of 6.76 ± 2.41 % compared to 2.98 ± 1.46 % in controls (p = 0.03). Additionally, the retention coefficient appeared lower at 82.2 ± 5.8 % in dogs with DMD compared to 90.5 ± 6.6 % in controls (p = 0.12). A discrete-time kinetic model of uptake and retention of contrast agent in perfusion CMRI shows potential for the study of DMD.     

Comparison of the myocardial clearance of endothelial progenitor cells injected early versus late into reperfused or sustained occlusion myocardial infarction

Stem cell transplantation following AMI has shown promise for the repair or reduction of the amount of myocardial injury. There is some evidence that these treatment effects appear to be directly correlated to cell residence time. This study aims to assess the effects of (a) the timing of stem cell injection following myocardial infarction, and (b) flow milieu, on cell residence times at the site of transplantation by comparing three time points (day of infarction, week 1 and week 4–5), and two models of acute myocardial infarction (sustained occlusion or reperfusion). Twenty-one dogs received 2 injections of 30 million endothelial progenitor cells. The first injections were administered by epicardial (n = 8) or endocardial injection (n = 13) either on the day of infarction (n = 15) or at 1 week (n = 6). The second injections were administered by only endocardial injection (n = 18) 4 weeks following the first injection. Cell clearance half-lives were comparable between early and late injections. However, transplants into sustained occlusion infarcts resulted in slower cell clearance 77.1 ± 6.1 (n = 18) versus reperfused 59.4 ± 2.9 h (n = 21) p = 0.009. Sustained occlusion infarcts had longer cell retention in comparison to reperfusion whereas the timing of injection did not affect clearance rates. If the potential for myocardial regeneration associated with cell transplantation is, at least in part, linked to cell residence times, then greater benefit may be observed with transplants into infarcts associated with persistent coronary artery occlusion.     

Assessment of microembolization associated with revascularization in acute myocardial infarction: MDCT cardiac perfusion and function study

To use multi-detector computed tomography (MDCT) for assessing the effects of coronary microemboli on pre-existing acute myocardial infarct (AMI) and to compare this pathology to LAD microembolization and occlusion/reperfusion. An angioplasty balloon catheter was placed in the LAD coronary artery of pigs under X-ray guidance. Four animals served as controls without intervention (group A) and an additional 24 animals (8/group) were subjected to microembolization (group B), occlusion/reperfusion (group C) or combination of the two insults (group D). MDCT was used to assess perfusion, LV function and viability. At postmortem, the LV sections were stained with hematoxylin/eosin and triphenyltetrazolium chloride (TTC). Dynamic perfusion and helical cine MDCT demonstrated decline in regional LV perfusion and function, respectively, after all interventions. MDCT showed significant differences in ejection fraction between groups: A = 57.5 ± 4.7 %, B = 40.3 ± 0.5 % P < 0.05, C = 34.9 ± 1.3 % P < 0.05 and D = 30.7 ± 1.2 % P < 0.05, while viability MDCT demonstrated differences in enhancement patterns and extents of damage between the groups (B = 9.1 ± 0.4 % LV mass, C = 11.9 ± 0.7 % and D = 16.2 ± 1.2 %, P < 0.05) and extent of microvascular obstruction (MVO) (group C = 3.2 ± 1.0 % LV mass versus D = 5.2 ± 0.7 %, P < 0.01). DE-MDCT overestimated all types of myocardial damage compared with TTC, but showed a close correlation (r > 0.7). Microscopic examination confirmed the presence of patchy and contiguous necrosis, MVO, edema and calcium deposits. Dynamic and helical cine MDCT imaging can grade LV dysfunction and perfusion deficit, respectively. DE-MDCT demonstrated a large and persistent MVO zone after microembolization of pre-existing AMI. Furthermore, it has the potential to visualize patchy microinfarct, detect perfusion deficits and dysfunction at the border zone after microembolization of pre-existing AMI.     

Sustained therapeutic perfusion outside transplanted sites in chronic myocardial infarction after stem cell transplantation

This study aimed at comparing long-term variations in the perfusion of chronic myocardial infarction (MI) areas after local injections of autologous bone marrow stem cells (BMSCs). 14 coronary ligated rats with transmural chronic MI (4 months) were used: a control group (n = 7) versus a treated group (n = 7) in which ¹¹¹In labeled-BMSCs were directly engrafted on MI areas. By using ¹¹¹In/^99mTc SPECT and Sestamibi gated-SPECT,. left ventricle perfusion and function were monitored in all animals by serial ^99mTc-Sestamibi pinhole gated-SPECT over a period of 6 months. Post-therapeutic myocardial perfusion improved as early as 48 h following injection in the 2 groups. This benefice was sustained during the 6-month follow-up in the non-engrafted MI-areas from treated rats (at 6-months: +10 ± 5 %), whereas the engrafted ones, as well as the MI areas from control rats, exhibited progressive deterioration over time (at 6-months: ?9 ± 10 % and ?5 ± 3 %, respectively). Perfusion enhancement of the chronic MI areas treated by BMSCs transplantation is: (1) marked in the following days, presumably because of an unspecific inflammatory reaction, and (2) sustained over the long term but only outside the sites of cell engraftment, suggesting a distant paracrine effect of transplanted cells.     

Improvement of myocardial perfusion reserve detected by cardiovascular magnetic resonance after direct endomyocardial implantation of autologous bone marrow cells in patients with severe coronary artery disease

Background

Recent studies suggested that bone marrow (BM) cell implantation in patients with severe chronic coronary artery disease (CAD) resulted in modest improvement in symptoms and cardiac function. This study sought to investigate the functional changes that occur within the chronic human ischaemic myocardium after direct endomyocardial BM cells implantation by cardiovascular magnetic resonance (CMR).

Methods and Results

We compared the interval changes of left ventricular ejection fraction (LVEF), myocardial perfusion reserve and the extent of myocardial scar by using late gadolinium enhancement CMR in 12 patients with severe CAD. CMR was performed at baseline and at 6 months after catheter-based direct endomyocardial autologous BM cell (n = 12) injection to viable ischaemic myocardium as guided by electromechanical mapping. In patients randomized to receive BM cell injection, there was significant decrease in percentage area of peri-infarct regions (-23.6%, P = 0.04) and increase in global LVEF (+9.0%, P = 0.02), the percentage of regional wall thickening (+13.1%, P= 0.04) and MPR (+0.25%, P = 0.03) over the target area at 6-months compared with baseline.

Conclusions

Direct endomyocardial implantation of autologous BM cells significantly improved global LVEF, regional wall thickening and myocardial perfusion reserve, and reduced percentage area of peri-infarct regions in patients with severe CAD.     

Head to head comparison of quantitative versus visual analysis of contrast CMR in the setting of myocardial stunning after STEMI: implications on late systolic function and patient outcome

To compare a quantitative assessment of contrast cardiovascular magnetic resonance (CMR) after ST-segment elevation myocardial infarction (STEMI) with visual analysis for predicting depressed ejection fraction (dEF) and major adverse cardiac events (MACE). 192 patients underwent CMR at 1 week and 6 months after STEMI. Three quantitative (initial slope, maximal signal intensity and contrast delay in first-pass imaging) and 2 visual perfusion indexes (hypoenhancement in first-pass and microvascular obstruction in late enhancement imaging (LE)) were determined. Quantification of infarct mass and visual assessment of the extent of transmural necrosis (ETN) were also performed. At 6 months, 69 patients displayed dEF. During follow-up (mean 655 days) 20 MACE (death, re-infarction, re-admission for heart failure) occurred. Perfusion quantification took longer (P < 0.001) and, in ROC curve analyses and the C-statistic, was not superior to visual perfusion analysis for predicting late EF or MACE (P = ns). Similarly, infarct size quantification was not superior to visual assessment of ETN (P = ns). In multivariate analyses, only visual assessment of ETN (per segment) predicted dEF (OR 1.30 95%CI [1.04–1.61], P = 0.02) and MACE (HR 1.38 95%CI [1.19–1.60], P < 0.001). Visual analysis of CMR after STEMI is not time consuming and predicts dEF and MACE comparable to quantification. ETN was the strongest parameter.     

Congenital Myocardial Sympathetic Dysinnervation (CMSD)—A Structural Defect of Idiopathic Long QT Syndrome

Concerning the pathogenetic mechanism of idiopathic long QT syndrome (LQTS), the hypothesis of a specific sympathetic imbalance has gained general acceptance, but its validity has never been proven. To test this hypothesis I-123-MIBG, an analogue of norepinephrine and guanethidine, was used to provide scintigraphic display of the efferent cardiac sympathetic innervation. Twelve members of four LQTS families (mean age 38.2 +/- 17.2 years, eight males) and eight healthy volunteers (mean age 48.2 +/- 13.3 years, five males) were studied by means of I-123-MIBG single photon emission computed tomography (SPECT). A quantitative analysis of all scans was performed. All scans of the healthy volunteers show a uniform tracer uptake with sometimes slightly decreased activity in the apex. (1) All patients with QTc greater than 440 msec (n = 5); (2) all, who had suffered from at least one episode of torsade de pointes, ventricular fibrillation (VF) or syncope (n = 5); and (3) all symptomatic patients with QTc prolongation (n = 4) have reduced or abolished (P less than 0.02) MIBG uptakes in the inferior and inferior septal parts of the left ventricle (congenital myocardial sympathetic dysinnervation [CMSD]). Additionally, one female without symptoms or QTc prolongation (LQT) shows an abnormal MIBG SPECT similar to the one of her daughter, who has LQT and symptoms. One male without LQT, who had suffered from VF shows CMSD similar to his father, who has LQT, but no symptoms. All members of the families with normal MIBG SPECTs have neither LQT nor symptoms. In all families CMSD fulfills the criteria of autosomal-dominant inheritance. Normal QTc-interval predicted only in 57% normal cardiac sympathetic innervation in the present LQTS families. Therefore, quantitative I-123-MIBG SPECT enables to identify myocardial sympathetic dysinnervation as structural defect in LQTS. CMSD is associated with and without LQT and presents a pattern of autosomal-dominant inheritance. LQT at rest or during exercise was specific (100%), but less sensitive (63%) in the assessment of CMSD than I-123-MIBG SPECT.     

Myocardial perfusion and adrenergic innervation in patients with RBBB and LAfB: the effect of altering the activation sequence with right ventricular apical pacing

The aim of this study was to investigate myocardial perfusion and adrenergic innervation in patients with intraventricular conduction disturbances and to detect any changes caused by alteration of the ventricular activation sequence as a result of right ventricular apical pacing. We studied 15 patients with right bundle branch block (RBBB) and left anterior fascicular block (LAFB), while 15 healthy individuals served as controls. All patients underwent planar and single-photon emission computed tomography (SPECT) myocardial imaging after intravenous infusion of 5mCi 123I-metaiodobenzylguanidine (123I-MIBG) and a SPECT thallium201 myocardial perfusion study before and 3 months after pacemaker implantation. The heart to mediastinum ratio was calculated during the 123I-MIBG study in order to assess the global cardiac sympathetic activity and was significantly smaller in patients than in controls (P < 0.001). Patients with RBBB and LAFB revealed regional adrenergic innervation defects, mostly in the inferior and posterior walls. After a medium-term pacing period, a redistribution of 123I-MIBG uptake was detected, with aggravation of adrenergic innervation defects in the apical and posterior walls and amelioration in septal and anterior walls. Five patients showed perfusion defects that remained unchanged after pacing. Two others displayed mild myocardial perfusion defects that did not exist before pacing. In conclusion, patients with RBBB and LAFB reveal global and regional disturbances of myocardial adrenergic innervation, which shows redistribution as a result of the altered propagation of the ventricular electrical activation. To a smaller degree these patients reveal myocardial perfusion disturbances in which pacing has a limited medium-term effect.     

Endocardial and epicardial myocardial perfusion determined by semi-quantitative and quantitative myocardial perfusion magnetic resonance

This study aims to quantify subendocardial and subepicardial myocardial blood flow (MBF) from dynamic contrast-enhanced MRI and to compare semi-quantitative and quantitative analysis methods. 17 healthy volunteers (9 males, mean age 34 ± 8) were scanned during adenosine stress and at rest. A “semi-quantitative” myocardial perfusion index (MPI) was calculated based on maximal upslopes of signal intensity-time profiles for a mid-ventricular myocardial slice. In addition, absolute MBF (ml/g/min) was estimated using Fermi-constrained deconvolution. On semi-quantitative analysis, the ratio of subendocardial to subepicardial MPI was 0.98 ± 0.1 at stress and 1.16 ± 0.09 at rest, P < 0.0001. The MPRI (i.e. the ratio of stress over rest MPI) for the subendocardium was 1.54 ± 0.3 versus 1.81 ± 0.35 for the subepicardium, P = 0.03. For quantitative analysis, the ratio of subendocardial to subepicardial MBF was 0.91 ± 0.11 at stress versus 1.17 ± 0.16 at rest, P < 0.0001. The subendocardial MBF reserve was also lower than in the subepicardium (2.6 ± 0.75 vs. 3.32 ± 0.93, P = 0.027). In conclusion, semi-quantitative and quantitative analysis of dynamic contrast-enhanced MRI shows higher subendocardial blood flow at rest and reduced subendocardial perfusion reserve compared to the subepicardium.     

Evaluation neointimal coverage in patients with coronary artery aneurysm formation after drug-eluting stent implantation by optical coherence tomography

The neointimal coverage in patients with coronary artery aneurysms (CAA) formation after drug eluting stent (DES) implantation is not clear. Total of 175 patients who had been implanted DES were identified. Patients were divided into the CAA group (n = 31) and non-CAA group (n = 144) based on the results of the coronary angiography. The cardiac events including angina and acute myocardial infarction were noted, in addition, the neointimal thickness and the frequence of strut malapposition and strut uncoverage were noted. A greater proportion of incomplete neointimal coverage (17.17 vs. 1.9 %, P < 0.001) and malapposition struts (18.2 vs. 1.38%, P < 0.001) were observed in the CAA group. 8 patients in CAA group underwent OCT examination twice in the period of follow-up. The proportion of incomplete neointimal coverage increased significantly as compared the second OCT results with the first examination (18.45 vs. 2.66 %, P < 0.001). Hyperplasia neointimal desquamated from struts and acquired struts incomplete neointimal coverage were detected. Patients with CAA had a higher frequency of cardiac events including angina pectoris (25.81 vs. 6.25 %, P = 0.001) and acute myocardial infarction (9.68 vs. 0.13 %, P = 0.002) and thrombosis (16.13 vs. 0.69 %, P < 0.001). The longitudinal length of CAA in cardiac event group was significantly longer than no cardiac event group (20.0 ± 9.07 vs. 12.05 ± 5.38 mm, P = 0.005). CAA formation after DES implantation frequently associated with cardiac events as a result of stent malapposition and incomplete neointimal coverage. Acquired incomplete neointimal coverage associated with CAA formation.     

Abnormal Cardiac Innervation in Patients with Idiopathic Ventricular Fibrillation

BIFFI, M., et al .: Abnormal Cardiac Innervation in Patients with Idiopathic Ventricular Fibrillation. Idiopathic ventricular fibrillation (VF) is diagnosed in up to nearly 10% of survivors of out-of-hospital cardiac arrest. The arrhythmogenic substrate is unknown. This study examined the role of cardiac innervation as a possible contributor to this arrhythmia. Eight patients with idiopathic VF were compared with eight normal subjects (controls) by [¹²³] I metaiodobenzylguanidine SPECT (MIBG), measuring peak uptake, late uptake, and clearance of the nuclear tracer. The left ventricle was divided in 13 segments in the bull's-eye target plot. Peak and late MIBG uptake was increased in the anterolateral segments (2,3,7,8) compared to the inferoposterior and septal segments, in controls and in patients. No difference was observed between controls and patients in the inferoposterior and septal segments. In contrast, a significantly higher MIBG uptake was observed in patients compared to controls in the anterolateral segments (   94 ± 4%   vs   81 ± 11%, P < 0.03   for peak uptake;   94 ± 5%   vs   79 ± 12%, P < 0.01   for late uptake). No difference was observed in MIBG clearance in any segment in either study group. Cardiac sympathetic innervation is highly heterogeneous, though predominant in anterolateral segments in normal subjects. Patients with idiopathic VF exhibit the same distribution, though have a significantly greater density of sympathetic terminals in the anterolateral segments than controls, which may promote ventricular arrhythmias. (PACE 2003; 26[Pt. II]:357–360)     

Comparison between accelerated and conventional dobutamine stress protocols for myocardial perfusion scintigraphy

The conventional dobutamine (Dob) stress protocol for myocardial perfusion scintigraphy (MPS) is long, with frequent adverse effects, and generally requires atropine injection to reach target heart rate. Atropine is usually administered at the end of the protocol, when adverse effects are more frequent. Earlier atropine injection may be useful to shorten the stress protocol and reduce adverse effects. We sought to compare a Dob stress protocol with early atropine injection to a conventional Dob stress protocol in the same patients undergoing MPS. 30 patients underwent Dob-MPS with a conventional protocol (steps of 10, 20, 30 and 40 mcg/kg/min at 3 min intervals, adding atropine to the maximal Dob dose if necessary to achieve 85% of the age-corrected maximal predicted heart rate) and with an accelerated protocol with early atropine injection (at the end of the first stage). We compared stress duration, maximal heart rate (HR), percentage of maximal predicted HR, rate-pressure product, ST changes, MPS scores and the incidence of adverse effects between the 2 protocols. The accelerated protocol was shorter than the conventional protocol (7.1 ± 3.4 min vs. 11.8 ± 1.3 min; P < 0.0001), had the same efficacy to achieve hemodynamic parameters, without increasing adverse effects. The summed stress scores obtained by automatic analysis were similar in both protocols (6.3 ± 6.3 vs. 6.8 ± 6.3; P = NS) as well as the summed difference scores (2.5 ± 3.6 vs. 2.7 ± 3.4; P = NS). Early atropine injection during dobutamine stress protocol shortens stress duration. Our results suggest that patient safety and accuracy of MPS are unaltered, when compared to the conventional protocol, but further, larger studies are still necessary.