Improvement In Regional Function Research Articles

P4322Prediction of regional functional improvement by multidetector computed tomography without contrast reinjection following percutaneous coronary intervention in acute myocardial infarction

P4322Prediction of regional functional improvement by multidetector computed tomography without contrast reinjection following percutaneous coronary intervention in acute myocardial infarction

Abstract 21: Quantification of Total Myocyte Regeneration Following Intracoronary Cardiosphere-Derived Cell (icCDC) Treatment in Swine with Chronic Myocardial Ischemia

Objective: icCDCs improve function of ischemic myocardium and increase cardiomyocyte nuclear density but the extent to which this is explained by an increase in nuclei per cell vs. the formation of new myocytes is unclear. We aimed to address this issue and quantify new myocyte formation throughout the left ventricle (LV) after global icCDC treatment in swine with hibernating myocardium. Methods: Swine with a chronic LAD stenosis (N=29) received either ~35 x 10 6 icCDCs or no treatment. Regional function (echocardiography) and myocyte morphometric indices were assessed 1 month later. Transverse and longitudinal tissue sections were used to measure regional myocyte nuclear density, diameter, length, and nuclei/cell, from which myocyte volume and myocytes per gram of myocardium were calculated. Results: icCDC-mediated improvements in regional function were accompanied by an increase in myocyte nuclear density without a change in the number of nuclei/cell (Table). Compared with untreated animals, icCDC-treated animals exhibited a reduction in myocyte volume and a reciprocal increase in the number of myocytes per gram of tissue. Anatomic LV hypertrophy did not occur, however, as LV mass/body mass ratio was not different between groups (untreated: 2.5 ± 0.1 vs. icCDCs: 2.3 ± 0.1). Conclusion: These data demonstrate that icCDCs produce significant myocyte regeneration throughout the regionally ischemic heart that is dissociated from alterations in LV mass. Changes in myocyte nuclear density do not reflect an altered number of nuclei/cell and quantitative estimates suggest that intracoronary delivery of CDCs to the entire LV increases the number of myocytes by ~25% in just 4 weeks.

Autologous Mesenchymal Stem Cells Produce Concordant Improvements in Regional Function, Tissue Perfusion, and Fibrotic Burden When Administered to Patients Undergoing Coronary Artery Bypass Grafting

Although accumulating data support the efficacy of intramyocardial cell-based therapy to improve left ventricular (LV) function in patients with chronic ischemic cardiomyopathy undergoing CABG, the underlying mechanism and impact of cell injection site remain controversial. Mesenchymal stem cells (MSCs) improve LV structure and function through several effects including reducing fibrosis, neoangiogenesis, and neomyogenesis. To test the hypothesis that the impact on cardiac structure and function after intramyocardial injections of autologous MSCs results from a concordance of prorecovery phenotypic effects. Six patients were injected with autologous MSCs into akinetic/hypokinetic myocardial territories not receiving bypass graft for clinical reasons. MRI was used to measure scar, perfusion, wall thickness, and contractility at baseline, at 3, 6, and 18 months and to compare structural and functional recovery in regions that received MSC injections alone, revascularization alone, or neither. A composite score of MRI variables was used to assess concordance of antifibrotic effects, perfusion, and contraction at different regions. After 18 months, subjects receiving MSCs exhibited increased LV ejection fraction (+9.4 ± 1.7%, P=0.0002) and decreased scar mass (-47.5 ± 8.1%; P<0.0001) compared with baseline. MSC-injected segments had concordant reduction in scar size, perfusion, and contractile improvement (concordant score: 2.93 ± 0.07), whereas revascularized (0.5 ± 0.21) and nontreated segments (-0.07 ± 0.34) demonstrated nonconcordant changes (P<0.0001 versus injected segments). Intramyocardial injection of autologous MSCs into akinetic yet nonrevascularized segments produces comprehensive regional functional restitution, which in turn drives improvement in global LV function. These findings, although inconclusive because of lack of placebo group, have important therapeutic and mechanistic hypothesis-generating implications. http://clinicaltrials.gov/show/NCT00587990. Unique identifier: NCT00587990.

Intracoronary Cardiosphere-Derived Cells After Myocardial Infarction: Evidence of Therapeutic Regeneration in the Final 1-Year Results of the CADUCEUS Trial (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction)

This study sought to report full 1-year results, detailed magnetic resonance imaging analysis, and determinants of efficacy in the prospective, randomized, controlled CADUCEUS (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction) trial. Cardiosphere-derived cells (CDCs) exerted regenerative effects at 6 months in the CADUCEUS trial. Complete results at the final 1-year endpoint are unknown. Autologous CDCs (12.5 to 25 × 10(6)) grown from endomyocardial biopsy specimens were infused via the intracoronary route in 17 patients with left ventricular dysfunction 1.5 to 3 months after myocardial infarction (MI) (plus 1 infused off-protocol 14 months post-MI). Eight patients were followed as routine-care control patients. In 13.4 months of follow-up, safety endpoints were equivalent between groups. At 1 year, magnetic resonance imaging revealed that CDC-treated patients had smaller scar size compared with control patients. Scar mass decreased and viable mass increased in CDC-treated patients but not in control patients. The single patient infused 14 months post-MI responded similarly. CDC therapy led to improved regional function of infarcted segments compared with control patients. Scar shrinkage correlated with an increase in viability and with improvement in regional function. Scar reduction correlated with baseline scar size but not with a history of temporally remote MI or time from MI to infusion. The changes in left ventricular ejection fraction in CDC-treated subjects were consistent with the natural relationship between scar size and ejection fraction post-MI. Intracoronary administration of autologous CDCs did not raise significant safety concerns. Preliminary indications of bioactivity include decreased scar size, increased viable myocardium, and improved regional function of infarcted myocardium at 1 year post-treatment. These results, which are consistent with therapeutic regeneration, merit further investigation in future trials. (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction [CADUCEUS]; NCT00893360).

Prediction of functional recovery after revascularization in patients with chronic ischemic myocardial dysfunction

In patients with chronic ischemic myocardial dysfunction, perfusable tissue index (PTI) obtained with positron emission tomography using oxygen-15-labeled water and carbon monoxide as tracers is inversely related to the extent of myocardial scar (nonperfusable tissue). Delayed contrast-enhanced (DCE) magnetic resonance imaging (MRI) accurately depicts the regional extent of myocardial fibrosis and predicts functional recovery after revascularization in patients with ischemic cardiomyopathy. Our aim was to compare PTI as a viability marker with DCE MRI. Fourteen patients with ischemic left ventricular dysfunction were studied with positron emission tomography, using oxygen-15-labeled water and carbon monoxide as tracers, and with contrast-enhanced MRI. Functional improvement occurred in 38 of initially dysfunctional, revascularized segments (56%). Mean PTI was 1.04 ± 0.20 in the improved segments versus 0.85 ± 0.21 in the group without functional improvement (P<0.001). The areas under the receiver operator characteristics curves of PTI and DCE MRI were 0.7 and 0.74, respectively (P=not significant). Cutoff value of 25% DCE allowed correct identification of 82% segments with reversible dysfunction and 64% segments without reversible dysfunction. A threshold of 0.89 for PTI yielded the best diagnostic accuracy with sensitivity and specificity values of 76 and 54%, respectively. PTI can identify viable myocardium and predict improvement in regional function after revascularization in patients with chronic ischemic left ventricular dysfunction. Its diagnostic accuracy is comparable with that of DCE MRI.

Intramyocardial Stem Cell Injection in Patients With Ischemic Cardiomyopathy

Rationale: Transcatheter, intramyocardial injections of bone marrow–derived cell therapy produces reverse remodeling in large animal models of ischemic cardiomyopathy. Objective: We used cardiac MRI (CMR) in patients with left ventricular (LV) dysfunction related to remote myocardial infarction (MI) to test the hypothesis that bone marrow progenitor cell injection causes functional recovery of scarred myocardium and reverse remodeling. Methods and Results: Eight patients (aged 57.2±13.3 years) received transendocardial, intramyocardial injection of autologous bone marrow progenitor cells (mononuclear or mesenchymal stem cells) in LV scar and border zone. All patients tolerated the procedure with no serious adverse events. CMR at 1 year demonstrated a decrease in end diastolic volume (208.7±20.4 versus 167.4±7.32 mL; P =0.03), a trend toward decreased end systolic volume (142.4±16.5 versus 107.6±7.4 mL; P =0.06), decreased infarct size ( P &lt;0.05), and improved regional LV function by peak Eulerian circumferential strain in the treated infarct zone (−8.1±1.0 versus −11.4±1.3; P =0.04). Improvements in regional function were evident at 3 months, whereas the changes in chamber dimensions were not significant until 6 months. Improved regional function in the infarct zone strongly correlated with reduction of end diastolic volume ( r 2 =0.69, P =0.04) and end systolic volume ( r 2 =0.83, P =0.01). Conclusions: These data suggest that transcatheter, intramyocardial injections of autologous bone marrow progenitor cells improve regional contractility of a chronic myocardial scar, and these changes predict subsequent reverse remodeling. The findings support the potential clinical benefits of this new treatment strategy and ongoing randomized clinical trials.

Does laser type impact myocardial function following transmyocardial laser revascularization?

Transmyocardial laser revascularization (TMR) is currently clinically performed with either a CO(2) or Ho:YAG laser for the treatment of severe angina. While both lasers provide symptomatic relief, there are significant differences in the laser-tissue interactions specific to each device that may impact their ability to enhance the perfusion of myocardium and thereby improve contractile function of the ischemic heart. A porcine model of chronic myocardial ischemia was employed. After collecting baseline functional data with cine magnetic resonance imaging (MRI) and dobutamine stress echo (DSE), 14 animals underwent TMR with either a CO(2) or Ho:YAG laser. Transmural channels were created with each laser in a distribution of 1/cm(2) in the ischemic zone. Six weeks post-treatment repeat MRI as well as DSE were obtained after which the animals were sacrificed. Histology was preformed to characterize the laser-tissue interaction. CO(2) TMR led to improvement in wall thickening in the ischemic area as seen with cine MRI (40.3% vs. baseline, P < 0.05) and DSE (20.2% increase vs. baseline, P < 0.05). Ho:YAG treated animals had no improvement in wall thickening by MRI (-11.6% vs. baseline, P = .67) and DSE (-16.7% vs. baseline, P = 0.08). Correlative semi-quantitative histology revealed a significantly higher fibrosis index in Ho:YAG treated myocardium versus CO(2) (1.81 vs. 0.083, P < 0.05). In a side-by-side comparison CO(2) TMR resulted in improved function of ischemic myocardium as assessed by MRI and echocardiography. Ho:YAG TMR led to no improvement in regional function likely due to concomitant increase in fibrosis in the lasered area.

The Effect of High-Dose Valsartan on Left Ventricular Function Following Primary Percutaneous Coronary Intervention

REFER TO THE PAGE 77-83 The study by Kim et al.1) revealed that while improvement of regional function by valsartan was more effective in the high-dose (160 or 320 mg) valsartan group, compared with the low-dose group, high-dose valsartan did not have effects on left ventricular ejection fraction (LVEF) and lift ventriculal (LV) size. Angiotensin-receptor blockers (ARBs) should be used in post-ST-segment elevation myocardial infarction (STEMI) patients with evidence of LV dysfunction who are intolerant to angiotensin-converting enzyme (ACE) inhibitors.2) ARBs reduce mortality and morbidity rates in patients with heart failure (HF) and reduced LVEF. Investigators of the Val-HeFT3) and CHARM4) trials reported that high doses of ARBs improved clinical outcomes. Recently, the HEAAL study5) demonstrated that high-dose (losartan 150 mg) is superior to low-dose ARB (losartan 50 mg) in patients with HF and reduced LVEF. In contrast to the latter ARB trials, the VALIANT study6) focused on patients with HF after acute myocardial infarction (MI) and demonstrated that a high-dose ARB (valsartan 320 mg) was not inferior to an ACE inhibitor (captopril 150 mg). However, the VALIANT study did not evaluate dose-dependent clinical outcomes. The study by Kim et al.1) is helpful to understand changes in dose-dependent LV remodeling. However, this study has several limitations in terms of dose-dependent echocardiographic changes. First, the study population size was too small to compare LVEF and LV size between two groups. In the VALIANT Echo study, the small improvement in LVEF was observed in 610 patients. Second, baseline LVEF was too high (mean EF 52.7 ± 8.1%) to evaluate LV remodeling, compared to other remodeling studies such as the VALIANT (EF ≤ 35%) and HEAAL (EF ≤ 40%) studies. Third, the results do not definitively answer the question of why improvement of segmental wall motion was better in the high-dose than in the low-dose group. If additional information, such as myocardial microcirculation by myocardial contrast echocardiography and drugs affecting LV function were provided, the results would be more convincing. Valsartan (Diovan) is an oral angiotensin II-receptor antagonist with specificity for the angiotensin II type 1 receptor subtype. It has been shown to attenuate the progression of chronic HF and to reduce mortality in patients with myocardial infarction. Although based on clinical trials high-dose ARB (Valsartan 160 mg BID) is recommended for the improvement of LV function in heart failure, low-dose ARB is preferred in clinical practice in patients with HF. The ARB dose may vary according to race and personal preferences. In the VALIANT study, discontinuation of valsartan (160 mg BID) was observed in 1,675 (34%) patients. However, in the study by Kim et al.1), discontinuation of high-dose valsartan was seen in 43 (68%) patients. By comparing two groups prospectively after randomization, the present study concludes that high-dose valsartan is more effective than low-dose valsartan in improving segmental wall motion. Even though this is a small study to compare dose-dependent echocardiographic LV remodeling, it reveals the benefit of high-dose treatment, which may allow recommendation of high-dose valsartan even in post-STEMI cases.

Quantification of regional functional improvement of infarcted myocardium after primary PTCA by contrast‐enhanced magnetic resonance imaging

To assess with cardiac magnetic resonance imaging (CMR) the relationship between treatment delay and improvement of regional left ventricular function after primary percutaneous transluminal coronary angioplasty (p-PTCA) for acute myocardial infarction (AMI). We performed cine- and late-enhancement (LE) CMR in 40 patients with first AMI after restoring TIMI 3 flow with p-PTCA and at a follow-up 4 months later. Infarcted segments were determined from LE images. Regional left ventricular function was quantified from cine-CMR images. Segmentation followed the American Heart Association 17-segments model. Patients were divided into groups with delay <3 hours, 3-6 hours, 6-12 hours, and a delay >12 hours. Segmental wall thickening (SWT) significantly iproved only in segments reperfused within 6 hours (P < 0.001). Follow-up SWT was significantly higher if segments were reperfused early (<3 hours: 74 +/- 4%, 3-6 hours: 57 +/- 4%, 6-12 hours: 48 +/- 7%, <3 to 3-6: P < 0.003, and <3 to 6-12 hours: P < 0.001). The extent of improvement was greater if delay was <3 hours compared to segments with a delay of >3 hours (<3 hours: +21 +/- 3%, 3-6 hours: +8 +/- 4%, 6-12 hours: +6 +/- 3%; <3 hours to 3-6 hours, and 6-12 h, P < 0.02). We quantitatively demonstrated that time to p-PTCA treatment significantly influences regional functional recovery of infarcted myocardium at a 4-month follow-up.

Positive effect of darbepoetin on peri-infarction remodeling in a porcine model of myocardial ischemia–reperfusion

Erythropoietin (Epo) has anti-apoptotic and pro-angiogenic effects in rodent models of myocardial infarction (MI). We tested the hypothesis that a long-acting Epo derivative (darbepoetin) has a beneficial effect on infarct size and peri-infarct remodeling in a clinically relevant large animal model of ischemia–reperfusion. A human acute MI scenario was simulated in 16 domestic pigs by inflating an angioplasty balloon in the proximal left circumflex (LCx) artery for 60 min. The animals were randomized to darbepoetin 30 μg/kg iv or placebo (saline) at the time of reperfusion. Treatment with darbepoetin did not lead to a reduction in the infarct size at 2 weeks as assessed by histology (30.3 ± 1.8% of the volume at risk for placebo vs. 33.2 ± 2.5% for darbepoetin). However, significant effects were seen in the peri-infarct region. Histological evaluation revealed decreased interstitial fibrosis (6.8 ± 0.7% of myocardial sections area vs. 9.6 ± 0.7%, p = 0.02) and increased average capillary area (106 ± 3% of the non-infarcted myocardium vs. 89 ± 4%, p = 0.003) in the treatment arm in the absence of significant cardiac hypertrophy. This resulted in preserved regional wall motion as assessed by tissue Doppler-derived radial strain (subepicardial radial strain 90.1 ± 21.2% for darbepoetin vs. 20.3 ± 10.1% for placebo, p < 0.05). However, this did not translate to improved wall thickening (126.5 ± 6.0% of diastolic thickness for darbepoetin vs. 119.8 ± 5.4% for placebo, p = NS). Beneficial effects of darbepoetin to peri-infarct remodeling were observed in a clinically relevant model of ischemia–reperfusion. Although the infarct size was not reduced, there was a limited decrease in interstitial fibrosis, increased capillary area and regional functional improvement in darbepoetin-treated animals.

Full Length Article

The purpose of this investigator-driven, prospective, randomized, double-blinded, placebo-controlled phase II study was to compare the effects of granulocyte colony-stimulating factor (G-CSF) on the improvement of myocardial function in patients undergoing delayed percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). Experimental and early clinical studies suggest that transplantation of stem cells improves cardiac regeneration and neovascularization after acute myocardial infarction. Most investigators have utilized either a direct injection or intracoronary infusion of bone marrow–derived cells, but early cytokine-mediated mobilization of stem cells has been reported to show similar improvement in cardiac function. Forty-four patients with late revascularized subacute STEMI were treated either with G-CSF or placebo over 5 days after successful PCI. Primary end points were change of global and regional myocardial function from baseline (1 week after PCI) to 3 months after PCI assessed by magnetic resonance imaging (MRI). Secondary end points consisted of characterization of mobilized stem cell populations, assessment of safety parameters up to 12 months including 6-month angiography, as well as myocardial perfusion assessed by MRI. Global myocardial function from baseline (1 week after PCI) to 3 months improved in both groups, but G-CSF was not superior to placebo (Δejection fraction6.2 ± 9.0 vs. 5.3 ± 9.8%, p = 0.77). A slight but non-significant improvement of regional function occurred in both groups. Granulocyte colony-stimulating factor resulted in mobilization of endothelial progenitor cell populations and was well tolerated with a similar rate of target lesion revascularization from in-stent restenosis. In both groups major adverse cardiovascular events occurred in a comparable frequency. Granulocyte colony-stimulating factor resulted in significant improvement of myocardial perfusion 1 week and 1 month after PCI. Granulocyte colony-stimulating factor treatment after PCI in subacute STEMI is feasible and relatively safe. However, patients do not benefit from G-CSF when PCI is performed late. Granulocyte colony-stimulating factor results in improved myocardial perfusion of the infarcted area, which may reflect enhanced neovascularization.

Autologous Bone Marrow Stem Cell Mobilization Induced by Granulocyte Colony-Stimulating Factor After Subacute ST-Segment Elevation Myocardial Infarction Undergoing Late Revascularization: Final Results From the G-CSF-STEMI (Granulocyte Colony-Stimulating Factor ST-Segment Elevation Myocardial Infarction) Trial

The purpose of this investigator-driven, prospective, randomized, double-blinded, placebo-controlled phase II study was to compare the effects of granulocyte colony-stimulating factor (G-CSF) on the improvement of myocardial function in patients undergoing delayed percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). Experimental and early clinical studies suggest that transplantation of stem cells improves cardiac regeneration and neovascularization after acute myocardial infarction. Most investigators have utilized either a direct injection or intracoronary infusion of bone marrow-derived cells, but early cytokine-mediated mobilization of stem cells has been reported to show similar improvement in cardiac function. Forty-four patients with late revascularized subacute STEMI were treated either with G-CSF or placebo over 5 days after successful PCI. Primary end points were change of global and regional myocardial function from baseline (1 week after PCI) to 3 months after PCI assessed by magnetic resonance imaging (MRI). Secondary end points consisted of characterization of mobilized stem cell populations, assessment of safety parameters up to 12 months including 6-month angiography, as well as myocardial perfusion assessed by MRI. Global myocardial function from baseline (1 week after PCI) to 3 months improved in both groups, but G-CSF was not superior to placebo (Delta(ejection fraction) 6.2 +/- 9.0 vs. 5.3 +/- 9.8%, p = 0.77). A slight but non-significant improvement of regional function occurred in both groups. Granulocyte colony-stimulating factor resulted in mobilization of endothelial progenitor cell populations and was well tolerated with a similar rate of target lesion revascularization from in-stent restenosis. In both groups major adverse cardiovascular events occurred in a comparable frequency. Granulocyte colony-stimulating factor resulted in significant improvement of myocardial perfusion 1 week and 1 month after PCI. Granulocyte colony-stimulating factor treatment after PCI in subacute STEMI is feasible and relatively safe. However, patients do not benefit from G-CSF when PCI is performed late. Granulocyte colony-stimulating factor results in improved myocardial perfusion of the infarcted area, which may reflect enhanced neovascularization.

Prediction of functional recovery after revascularization in patients with coronary artery disease and left ventricular dysfunction by gated FDG-PET

Traditionally, cardiac fluorodeoxyglucose (FDG) uptake is combined with regional perfusion for optimal evaluation of viability. Gated FDG-positron emission tomography (PET) may be an alternative technique for detection of viability because it permits combined assessment of glucose metabolism uptake and wall thickening (WT). In this study the value of FDG uptake and WT (analyzed from a stand-alone gated FDG-PET study) for the prediction of recovery of regional and global left ventricular (LV) function in patients with coronary artery disease undergoing revascularization is studied. Thirty-eight patients with chronic coronary artery disease and LV dysfunction were included. Patients underwent gated FDG-PET to assess viability. Magnetic resonance imaging was performed before and 6 months after revascularization to assess regional and global LV function and LV volumes. Of the 213 revascularized dysfunctional segments, 133 (62%) exhibited functional recovery on follow-up magnetic resonance imaging. Receiver operating characteristic curve analysis indicated that a cutoff level for FDG uptake of 50% or greater yielded a sensitivity and specificity of 93% and 85%, respectively, on gated FDG-PET for prediction of improvement in regional function. Similarly, a cutoff level of 10% or greater for WT was optimal with a sensitivity and specificity of 89% and 78%, respectively. Improvement in LV ejection fraction was best predicted by the number of viable segments. Reverse LV remodeling could be predicted with a sensitivity and specificity of 89% and 65%, respectively, by use of FDG uptake of 50% or greater and 78% and 70%, respectively, by use of WT of 10% or greater. Accurate prediction of outcome after revascularization (including improvement in regional and global LV function and reverse remodeling) is possible with gated FDG-PET by use of a threshold of 50% or greater for FDG uptake or a threshold of 10% or greater for WT.

The presence of contractile reserve has no predictive value for the evolution of left ventricular function following atrio-ventricular node ablation in patients with permanent atrial fibrillation

Transcatheter ablation of the atrio-ventricular (AV) node followed by ventricular pacing has been shown to improve symptoms and quality of life (QOL) of patients with permanent atrial fibrillation (AF). In a considerable number of patients, cardiac function deteriorates after AV node ablation. We aimed to determine whether the absence of contractile reserve assessed by low dose dobutamine stress echocardiography (LDDSE) could identify those patients whose left ventricular (LV) function deteriorates after AV node ablation. All 25 patients studied had permanent AF for at least 12 months. LVEF was determined 6 days and 3 months after AV node ablation by radionuclide ventriculography (RNV), at a paced rate of 80 beats/min. Deterioration in cardiac function was defined as a decrease in LVEF>5%. LDSE was performed in all patients before and after ablation. The presence of contractile reserve was defined as an improvement in regional function of >or=1 grade at low dose dobutamine in at least 4 segments. QOL measurements were taken using Minnesota, NHBP and MPWB questionnaires. LVEF showed no improvement in the overall group (52.8+/-11.1% vs. 51.8+/-9.8%, p=NS). QOL showed significant improvement in all questionnaires (Minnesota: 4.1+/-2.1 vs. 2.5+/-2, p=0.001; NHBP: 54.8+/-43.3 vs. 34.2+/-34.3, p=0.002; MPWB: 22.2+/-4.6 vs. 19.4+/-6.2, p=0.03). There was no significant difference in change of LVEF between patients with and without contractile reserve (-0.4+/-8.7 vs. 1.6+/-11.3, p=NS). However, patients with a preserved LVEF at baseline showed more frequently a reduced LVEF after AV node ablation (62.2+/-10.4% vs. 47.5+/-7.6%, p=0.001). (1) The absence of contractile reserve does not predict deterioration of cardiac function after AV node ablation. (2) AV node ablation results in a significant improvement in QOL, which is not necessarily associated with improvement of LVEF. (3) Higher baseline LVEF predicts deterioration of cardiac function. These data suggest that although AV node ablation is an excellent way of controlling symptoms, it should be avoided in patients with normal LV function.

Delayed contrast-enhanced magnetic resonance imaging for the prediction of regional functional improvement after acute myocardial infarction

ObjectivesWe evaluated whether delayed contrast-enhanced magnetic resonance imaging (DCE-MRI) using an extracellular contrast agent could predict improvement of dysfunctional but viable myocardium after acute reperfused myocardial infarction (MI). BackgroundThe transmural extent of hyperenhancement at DCE-MRI has been related to improvement of function in reperfused MI. However, evidence is still limited, and earlier reports have produced conflicting results regarding the significance of contrast patterns after infarction. MethodsThirty patients (mean age 59 ± 11 years, 27 males) underwent cine MRI and DCE-MRI 7 ± 3 days after a first reperfused acute MI and follow-up cine MRI at 13 ± 3 weeks. Segmental wall thickening and segmental extent of hyperenhancement were scored in 1,689 segments. ResultsOf 500 dysfunctional segments, 273 (55%) improved at follow-up. There was no difference in likelihood of improvement or complete functional recovery between segments with 0% and 1% to 25% hyperenhancement. The likelihood of improvement of segments without hyperenhancement was 2.9, 14.3, and 20 times higher than that of segments with 26% to 50%, 51% to 75%, and >75% hyperenhancement, respectively (p < 0.001). The likelihood of complete functional recovery of segments without hyperenhancement was 3.8, 11.1, and 50 times higher than that of segments with 26% to 50%, 51% to 75%, and >75% hyperenhancement, respectively (p < 0.001). ConclusionsIn patients with recent reperfused MI, functional improvement of stunned myocardium is predicted by DCE-MRI.

Is There a Long-Term Predictive Value of Intraoperative Low-Dose Dobutamine Echocardiography in Patients Who Have Coronary Artery Bypass Graft Surgery with Cardiopulmonary Bypass?

In patients with coronary artery disease, chronic regional left ventricular systolic dysfunction at rest may be caused by hibernating or by infarcted myocardium. Intraoperative low-dose dobutamine (LDD) echocardiography reliably predicts the immediate recovery of regional myocardial function after coronary artery bypass graft (CABG) surgery. We sought to determine whether intraoperative LDD echocardiography would also predict recovery of regional function after 1 yr. Twenty-five patients with coronary artery disease who underwent CABG surgery with intraoperative LDD echocardiography were evaluated 1 yr later with a follow-up transthoracic echocardiogram. The covariates of left ventricular ejection fraction, old myocardial infarction, and diabetes mellitus were considered in an analysis of regional wall motion (RWM). A 16-segment model and a 1–5-point scoring system were used to evaluate 350 myocardial segments. Multiple logistic regression analysis was performed to determine whether response to intraoperative LDD echocardiography (5 μg · kg−1 · min−1) predicted changes in regional function at 1 yr. A segment was defined as stunned if the RWM score obtained during LDD infusion deteriorated after cardiopulmonary bypass but recovered in the 1-yr follow-up echocardiogram. A response to intraoperative LDD predicted changes in regional function at 1 yr. The overall odds of improvement in regional function were 2.22 times greater (95% confidence interval = 1.29, 3.82;P = 0.0039) with a positive response to intraoperative LDD. The positive predictive value of intraoperative LDD echocardiography for improvement in myocardial function was 0.81 and the negative predictive value was 0.34. The predictive values did not vary with the examined covariates. Of segments with unexpected deterioration of RWM immediately after cardiopulmonary bypass, 87% recovered at the time of the 1-yr follow-up echocardiogram. Contractile reserve demonstrated by intraoperative LDD echocardiography predicts regional function at 1 yr; however, the test cannot predict which segment will not recover. Most of unexpected regional ventricular systolic dysfunction immediately after CABG surgery can be attributed to myocardial stunning.

Prediction of long-term effects of revascularization on regional and global left ventricular function by dobutamine echocardiography and rest Tl-201 imaging alone and in combination in patients with chronic coronary artery disease

Background. The aim of this study was to evaluate the accuracy of low-dose dobutamine echocardiography (DE) and resting thallium 201 single photon emission computed tomography (SPECT) alone and in combination for prediction of functional recovery at late follow-up (1 year) after revascularization. Methods and Results. Twenty-six patients with coronary artery disease and ventricular dysfunction (ejection fraction, 42% ± 9%) underwent DE and Tl-201 SPECT 14 ± 9 (mean ± SD) days before revascularization and repeated echocardiography 12 ± 5 months thereafter. Discriminant analysis was applied to combine Tl-201 SPECT and DE data to classify dysfunctional segments as viable or nonviable. In 78 akinetic/dyskinetic revascularized segments, Tl-201 SPECT provided a sensitivity of 83% and a specificity of 55%, whereas DE showed a sensitivity of 60% and a specificity of 91%, for prediction of improvement in regional function at follow-up. The combination of data through use of discriminant analysis provided a sensitivity of 80% and a specificity of 86%, with an overall accuracy of 82%, significantly higher than DE (71%; P < .05) and Tl-201 SPECT (73%; P < .05) alone. Moreover, discriminant analysis identified 12 (75%) of 16 patients with and 8 (80%) of 10 patients without significant improvement in ejection fraction at follow-up, with an accuracy of 77%. Conclusions. The combination of Tl-201 SPECT and DE data provides higher accuracy than either technique alone for prediction of recovery of regional and global function after revascularization. (J Nucl Cardiol 2002;9:174-82.)

Correction

HomeCirculationVol. 104, No. 25Correction Free AccessCorrectionPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessCorrectionPDF/EPUBCorrection Originally published17 Dec 2001https://doi.org/10.1161/circ.104.25.3179Circulation. 2001;104:3179The following abstract, “Electromechanical Mapping Predicts Improvement of Regional Ventricular Function in Patients With Ischemic Cardiomyopathy Undergoing Revascularization,” by Samady et al was inadvertently left out of the Scientific Sessions Abstracts supplement (Circulation. 2001;104 [suppl II]). The abstract is published in its entirety below.MPS.64.1 Myocardial Viability Assessment in Nuclear Cardiology Wednesday, 11/14/20019:00 AM to 11:30 AMTeam–Team 0064B114125Electromechanical Mapping Predicts Improvement of Regional Ventricular Function in Patients With Ischemic Cardiomyopathy Undergoing RevascularizationHabib Samady, C Joon Choi, Michael Ragosta, Eric R Powers, Allen R Goode, Ian J Sarembock, Lawrence W Gimple, Jennifer Hunter, George A Beller, Christopher M Kramer, Denny D Watson, University of Virginia, Charlottesville, VABackground: Markers of myocardial viability assessed by left ventricular electromechanical mapping (EMM) have been shown to correlate with non-invasive parameters of viability asessment. Whether EMM can predict improvement in regional function after myocardial revascularization is not known. Methods: Accordingly, 15 patients (12 males, age 62±8 yrs) with ischemic LV dysfunction (LVEF 0.30±0.11) underwent EMM before revascularization. Linear local shortening (LLS), unipolar voltage (UpV), and Viability Index (VI), defined as LLS x UpV/10, were measured by EMM. All patients underwent Dipyridamole/Rest gated-SPECT sestamibi (G-SPECT) before and after revascularization to measure global LVEF and regional thickening fractions (TF). Both EMM and G-SPECT images were divided into fourteen corresponding segments for comparative analysis. Results: LVEF increased from 0.30±0.11 to 0.38±0.11 (p=0.001) 4±2 months after revascularization. Of 210 available segments,199 were revascularized and had adequate data for analysis. Fifty segments with normal baseline function were excluded. Of 149 hypokinetic or akinetic segments, 63 improved function (TF 12±13% to 25±12%, P=0.001)and 86 did not (TF 11±9% to 12±10%, P=NS). Table compares EMM variables in segements which improved function to those which did not improve function after revascularization. Logistic regression analysis showed UpV and VI to be predictive of improvement of regional function (P= 0.02). A UpV of 9.6 mV had a 64% sensitivity and a 71% specificity, and a VI index of 5.0 mV% had a 61% sensitivity and 64% specificity for detecting improvement of regional function by G-SPECT. Conclusion: EMM markers of myocardial viability are predictive of improvement of regional ventricular function after revascularization in patients with ischemic cardiomyopathy. Improved Function (n=63)Not Improved Function (n=86)PLLS (%)6.6±6.65.7±5.2NSUpV (mV)9.6±5.37.8±4.10.02VI (mV%)7.8±104.6±5.50.01 Previous Back to top Next FiguresReferencesRelatedDetails December 17, 2001Vol 104, Issue 25 Advertisement Article InformationMetrics https://doi.org/10.1161/circ.104.25.3179 Originally publishedDecember 17, 2001 PDF download Advertisement

Assessment of myocardial viability by 31P-MR-spectroscopy and 23Na-MR imaging.

An exact differentiation between viable (hibernating or stunned) and non-viable (scar) tissue is crucial for the decision whether revascularisation is required after myocardial infarction [I]. Former studies demonstrated altered energy metabolism in ischemic myocardium [2]. 3~p-MR-Spectroscopy offers the unique possibility for non-invasive study of cardiac energy metabolism. Aim of the present work was to analyze whether a reliable detection of myocardial viability is possible by 3tp-MRSpectroscopy. All examinations were performed on a 1.5 Tesla clinical MR system (Magnetom VISION, Siemens, Erlangen). 3~p-spectra were acquired using a double-resonant 3~p/~H-surface coil and a double-angulated 3D-CSI-technique (voxelsize 25 ccm). Due to the limited sensitivity for the deeper parts of the heart only patients with anterior wall infarction were included (n=20) . For each patient 3~P-spectra from the infarcted area were compared to 3~p-spectra from non-infarcted septat myocardium (internal reference). Additionally, left ventricular function was analyzed by short axis cine-MRI breath-hold sequences (slice thickness 8 mm). Both examinations were performed at study entry (3 weeks after acute myocardial infarction) and 3 months after revascularization. Improvement of regional function in MRI was used as gold standard for viability [3]. Aged-matched healthy volunteers (n = 10) served as control group. Using the AMARES software

Assessment of perfusion, function, and myocardial metabolism after infarction with a combination of low-dose dobutamine tetrofosmin gated SPECT perfusion scintigraphy and BMIPP SPECT imaging

Background. Tetrofosmin gated single photon emission computed tomography (SPECT) allows simultaneous assessment of regional myocardial perfusion, global and regional left ventricular function, and function at rest and during pharmacologic intervention. SPECT with fatty acid analogues, such as β-methyl-iodophenyl-pentadecanoic acid (BMIPP), can be used to monitor metabolic changes induced by myocardial ischemia. In this work, the results of both studies obtained in patients with recent myocardial infarction are integrated. Methods. Twenty patients underwent tetrofosmin and BMIPP scintigraphy with a 3-head camera. Two consecutive tetrofosmin gated SPECT acquisitions were performed 60 minutes after administration of technetium-99m tetrofosmin (925 MBq) at rest (3 × 20 stops of 9 s; matrix 64 × 64 over 360°. One acquisition was made at rest, and the second was made during dobutamine infusion (10 μg/kg/min). Regional functional abnormalities were quantified and expressed as wall thickening severity (WTsev) in arbitrary units. Left ventricular ejection fraction and volumes were assessed with the Cedars Sinai algorithm. BMIPP imaging started 20 minutes after iodine 123-BMIPP (150 MBq) administration at rest (3 × 32 stops of 60 s; matrix 64 × 64 over 360°; medium energy collimators). Tracer uptake was scored according to a 25-segment model. Results. Sixteen of 18 patients had regional functional abnormalities at baseline (average WTsev 13.7 units). The WTsev score at baseline correlated well with the degree of residual perfusion. During dobutamine infusion, WTsev did not change (from 23.4 to 23.6 units) in 5 patients; it decreased (from 16.1 to 5.9 units) in 11 patients; and it increased (from 13.0 to 22.3 units) in 3 patients. An increase or decrease in WTsev during dobutamine infusion was associated with the presence of a considerable amount of BMIPP mismatched myocardium, whereas no change in WTsev was preferentially associated with a BMIPP matched pattern and perfusion defects with a higher severity score. Conclusion. Immediately after infarction, the severity of regional dysfunction at rest correlated well with the perfusion defect severity. Improvement in regional function during dobutamine administration is associated with less severe perfusion defects and a considerable amount of BMIPP mismatched myocardium, both suggesting viability. (J Nucl Cardiol 2000;7:29–36.)