Petra Dibbets-Schneider

Intramyocardial Bone Marrow Cell Injection for Chronic Myocardial Ischemia: A Randomized Controlled Trial

CONTEXT Previous studies have suggested that bone marrow cell injection may improve myocardial perfusion and left ventricular (LV) function in patients with chronic myocardial ischemia. OBJECTIVE To investigate the effect of intramyocardial bone marrow cell injection on myocardial perfusion and LV function in patients with chronic myocardial ischemia. DESIGN, SETTING, AND PATIENTS Randomized, double-blind, placebo-controlled trial at a Netherlands university hospital, May 1, 2005-March 3, 2008 (6-month follow-up ended September 2008) of 50 patients with chronic myocardial ischemia (mean age [SD], 64 [8] years; 43 men). INCLUSION CRITERIA severe angina pectoris despite optimal medical therapy and myocardial ischemia. All patients were ineligible for conventional revascularization. INTERVENTIONS Intramyocardial injection of 100 x 10(6) autologous bone marrow-derived mononuclear cells or placebo solution. MAIN OUTCOME MEASURES Primarily, the summed stress score, a 17-segment score for stress myocardial perfusion assessed by Tc-99m tetrofosmin single-photon emission computed tomography (SPECT). Secondary included LV ejection fraction (LVEF), Canadian Cardiovascular Society (CCS) class, and Seattle Angina Questionnaire quality-of-life score (mean difference >5% considered clinically significant). RESULTS After 3-month follow-up, the summed stress score (mean [SD]) improved from 23.5 (4.7) to 20.1 (4.6) (P < .001) in the bone marrow cell group, compared with a decrease from 24.8 (5.5) to 23.7 (5.4) (P = .004) in the placebo group. In the bone marrow cell-treated patients who underwent magnetic resonance imaging (MRI), a 3% absolute increase in LVEF was observed at 3 months (95% CI, 0.5% to 4.7%; n = 18), but the placebo group showed no improvement. CCS angina score improved significantly in the bone marrow cell group (6-month absolute difference, -0.79; 95% CI, -1.10 to -0.48; P < .001) compared with no significant improvement in the placebo group. Quality-of-life score increased from 56% (9%) to 64% (12%) at 3 months and 69% (12%) at 6 months in bone marrow cell-treated patients, compared with a smaller increase in the placebo group from 57% (11%) to 61% (14%) to 64% (17%). The improvements in CCS class and quality of life score were significantly greater in bone marrow cell-treated patients than in placebo-treated patients (P = .03 and P = .04, respectively). CONCLUSIONS In this short-term study of patients with chronic myocardial ischemia refractory to medical treatment, intramyocardial bone marrow cell injection resulted in a statistically significant but modest improvement in myocardial perfusion compared with placebo. Further studies are required to assess long-term results and efficacy for mortality and morbidity. TRIAL REGISTRATIONS trialregister.nl Identifier: NTR400 and isrctn.org Identifier: ISRCTN58194927.

Cardiac Sympathetic Denervation Assessed With 123-Iodine Metaiodobenzylguanidine Imaging Predicts Ventricular Arrhythmias in Implantable Cardioverter-Defibrillator Patients

OBJECTIVES The purpose of this study was to evaluate whether 123-iodine metaiodobenzylguanidine (123-I MIBG) imaging predicts ventricular arrhythmias causing appropriate implantable cardioverter-defibrillator (ICD) therapy (primary end point) and the composite of appropriate ICD therapy or cardiac death (secondary end point). BACKGROUND Although cardiac sympathetic denervation is associated with ventricular arrhythmias, limited data are available on the predictive value of sympathetic nerve imaging with 123-I MIBG on the occurrence of arrhythmias. METHODS Before ICD implantation, patients underwent 123-I MIBG and myocardial perfusion imaging. Early and late 123-I MIBG (planar and single-photon emission computed tomography [SPECT]) imaging was performed to assess cardiac innervation (heart-to-mediastinum ratio, cardiac washout rate, and 123-I MIBG SPECT defect score). Stress-rest myocardial perfusion imaging was performed to assess myocardial infarction and perfusion abnormalities (perfusion defect scores). During follow-up, appropriate ICD therapy and cardiac death were documented. RESULTS One-hundred sixteen heart failure patients referred for ICD therapy were enrolled. During a mean follow-up of 23 +/- 15 months, appropriate ICD therapy (primary end point) was documented in 24 (21%) patients and appropriate ICD therapy or cardiac death (secondary end point) in 32 (28%) patients. Late 123-I MIBG SPECT defect score was an independent predictor for both end points. Patients with a large late 123-I MIBG SPECT defect (summed score >26) showed significantly more appropriate ICD therapy (52% vs. 5%, p < 0.01) and appropriate ICD therapy or cardiac death (57% vs. 10%, p < 0.01) than patients with a small defect (summed score </=26) at 3-year follow-up. CONCLUSIONS Cardiac sympathetic denervation predicts ventricular arrhythmias causing appropriate ICD therapy as well as the composite of appropriate ICD therapy or cardiac death.

Can LV Dyssynchrony as Assessed with Phase Analysis on Gated Myocardial Perfusion SPECT Predict Response to CRT

Cardiac resynchronization therapy (CRT) is now a well-recognized therapeutic option for patients with end-stage heart failure. However, not all patients respond to CRT, and, therefore, preimplantation identification of responders is desirable. The aim of the present study was to investigate whether the degree of left ventricular (LV) dyssynchrony, as assessed with phase analysis from gated myocardial perfusion SPECT (GMPS), can predict which patients will respond to CRT. Methods: Forty-two patients with severe heart failure, depressed LV ejection fraction, and wide QRS complex were prospectively included for implantation of a CRT device and underwent GMPS and 2-dimensional echocardiography as part of the clinical protocol. Clinical status was evaluated using the New York Heart Association (NYHA) classification, 6-min walk test, and quality-of-life score. The histogram bandwidth and phase SD (parameters indicating LV dyssynchrony) were assessed from GMPS, and the clinical status and echocardiographic variables were reassessed at 6-mo follow-up. Results: Responders (71%) and nonresponders (29%) had comparable baseline characteristics, except for histogram bandwidth (175° ± 63° vs. 117° ± 51° [P < 0.01]) and phase SD (56.3° ± 19.9° vs. 37°.1 ± 14.4° [P < 0.01]), which were significantly larger in responders compared with nonresponders. Moreover, receiver-operating-characteristic curve analysis demonstrated an optimal cutoff value of 135° for histogram bandwidth (sensitivity and specificity of 70%) and of 43° for phase SD (sensitivity and specificity of 74%) for the prediction of response to CRT. Conclusion: Response to CRT is related to the presence of LV dyssynchrony assessed by phase analysis with GMPS. A cutoff value of 135° for histogram bandwidth and of 43° for phase SD could be used to predict response to CRT. Larger prospective studies are warranted to confirm the present findings.

Quantitative Gated SPECT–Derived Phase Analysis on Gated Myocardial Perfusion SPECT Detects Left Ventricular Dyssynchrony and Predicts Response to Cardiac Resynchronization Therapy

The significance of left ventricular (LV) dyssynchrony for the prediction of response to cardiac resynchronization therapy (CRT) has been demonstrated. Parameters reflecting LV dyssynchrony (phase SD, histogram bandwidth) can be derived from gated myocardial perfusion SPECT (GMPS) using phase analysis. The feasibility of LV dyssynchrony assessment with phase analysis on GMPS using Quantitative Gated SPECT (QGS) software has not been demonstrated in patients undergoing CRT. The aim of the present study was to validate the QGS algorithm for phase analysis on GMPS in a direct comparison with echocardiography using tissue Doppler imaging (TDI) for LV dyssynchrony assessment. Also, prediction of response to CRT using GMPS and phase analysis was evaluated. Methods: Patients (n = 40) with severe heart failure (New York Heart Association class III–IV), an LV ejection fraction of no more than 35%, and a QRS complex greater than or equal to 120 ms were evaluated for LV dyssynchrony using GMPS and echocardiography with TDI. At baseline and after 6 mo of CRT, clinical status, LV volumes, and LV ejection fraction were evaluated. Patients with functional improvement were classified as CRT responders. Results: Both histogram bandwidth (r = 0.69, r2 = 0.48, SEE = 25.4, P < 0.01) and phase SD (r = 0.65, r2 = 0.42, SEE = 26.8, P < 0.01) derived from GMPS correlated significantly with TDI for assessment of LV dyssynchrony. At baseline, CRT responders showed a significantly larger histogram bandwidth (94° ± 23° vs. 68° ± 21°, P < 0.01) and a larger phase SD (26° ± 6° vs. 18° ± 5°, P < 0.01) than did nonresponders. Receiver-operating-characteristic curve analysis identified an optimal cutoff value of 72.5° for histogram bandwidth to predict CRT response, yielding a sensitivity of 83% and a specificity of 81%. For phase SD, sensitivity and specificity similar to those for histogram bandwidth were obtained at a cutoff value of 19.6°. Conclusion: QGS phase analysis on GMPS correlated significantly with TDI for the assessment of LV dyssynchrony. Moreover, a high accuracy for prediction of response to CRT was obtained using either histogram bandwidth or phase SD.

Different manifestations of coronary artery disease by stress SPECT myocardial perfusion imaging, coronary calcium scoring, and multislice CT coronary angiography in asymptomatic patients with type 2 diabetes mellitus.

AbstractBackground. We sought to assess prospectively the evidence for silent coronary artery disease (CAD) in asymptomatic patients with type 2 diabetes mellitus by stress single-photon emission computed tomography (SPECT) myocardial perfusion imaging, coronary artery calcium (CAC) scoring, and multislice computed tomographic (MSCT) coronary angiography. Methods. One hundred asymptomatic patients (aged 30 to 72 years) with type 2 diabetes mellitus and one or more risk factors for CAD were prospectively recruited from an outpatient diabetes clinic. All patients underwent adenosine technetium-99m sestamibi SPECT imaging, CAC scoring, and 64-slice MSCT coronary angiography. Results. Twenty-three patients (23%) had abnormal stress SPECT imaging, consistent with inducible myocardial ischemia, whereas 60 patients (60%) had positive CAC scoring (18 patients [18%] with significant CAC >401), and 70 patients (70%) had abnormal MSCT coronary angiography (24 patients [24%] with significant, ≥50% stenosis). Of 77 patients with normal SPECT, 44 had a positive CAC score (10 patients [13%] >401), and 54 showed CAD on MSCT angiography (16 patients [21%] with ≥50% stenosis). Of 23 patients with an abnormal SPECT, 16 patients had a positive CAC score (8 patients [35%] >401), and 16 patients had CAD on MSCT angiography (8 patients [35%] with ≥50% stenosis). Overall, 17 patients (17%) had more than 2 significantly abnormal diagnostic test results, and 5 patients had three tests with significantly abnormal results. Conclusions. In this cohort of asymptomatic patients with type 2 diabetes mellitus, different modalities visualized different aspects of silent coronary atherosclerosis. Anatomic evidence of coronary atherosclerosis (CAC and MSCT) occurred more frequently than functional evidence (stress SPECT). However, clinically significant manifestations of CAD were observed in about one-quarter to one-fifth of patients by each modality, either separately or combined. The relative prognostic value of each modality needs to be determined by a follow-up of this cohort.

Cardiac autonomic neuropathy in patients with diabetes and no symptoms of coronary artery disease: comparison of 123I-metaiodobenzylguanidine myocardial scintigraphy and heart rate variability

PurposeThe purpose of this study was to evaluate the prevalence of cardiac autonomic neuropathy (CAN) in a cohort of patients with type 2 diabetes, truly asymptomatic for coronary artery disease (CAD), using heart rate variability (HRV) and 123I-metaiodobenzylguanidine (123I-mIBG) myocardial scintigraphy.MethodsThe study group comprised 88 patients with type 2 diabetes prospectively recruited from an outpatient diabetes clinic. In all patients myocardial perfusion scintigraphy, CAN by HRV and 123I-mIBG myocardial scintigraphy were performed. Two or more abnormal tests were defined as CAN-positive (ECG-based CAN) and one or fewer as CAN-negative. CAN assessed by 123I-mIBG scintigraphy was defined as abnormal if the heart-to-mediastinum ratio was <1.8, the washout rate was >25%, or the total defect score was >13.ResultsThe prevalence of CAN in patients asymptomatic for CAD with type 2 diabetes and normal myocardial perfusion assessed by HRV and 123I-mIBG scintigraphy was respectively, 27% and 58%. Furthermore, in almost half of patients with normal HRV, 123I-mIBG scintigraphy showed CAN.ConclusionThe current study revealed a high prevalence of CAN in patients with type 2 diabetes. Secondly, disagreement between HRV and 123I-mIBG scintigraphy for the assessment of CAN was observed.

Agreement and disagreement between contrast-enhanced magnetic resonance imaging and nuclear imaging for assessment of myocardial viability

PurposeThe purpose of this study was to compare contrast-enhanced MRI and nuclear imaging with 99mTc-tetrofosmin and 18F-fluorodeoxyglucose (18F-FDG) single photon emission computed tomography (SPECT) for assessment of myocardial viability.MethodsIncluded in the study were 60 patients with severe ischaemic left ventricular (LV) dysfunction who underwent contrast-enhanced MRI, 99mTc-tetrofosmin and 18F-FDG SPECT. Myocardial segments were assigned a wall motion score from 0 (normokinesia) to 4 (dyskinesia) and a scar score from 0 (no scar) to 4 (76–100% transmural extent). Furthermore, 99mTc-tetrofosmin and 18F-FDG segmental tracer uptake was categorized from 0 (tracer activity >75%) to 3 (tracer activity <25%). Dysfunctional segments were classified into viability patterns on SPECT: normal perfusion/18F-FDG uptake, perfusion/18F-FDG mismatch, and mild or severe perfusion/18F-FDG match.ResultsMinimal scar tissue was observed on contrast-enhanced MRI (scar score 0.4±0.8) in segments with normal perfusion/18F-FDG uptake, whereas extensive scar tissue (scar score 3.1±1.0) was noted in segments with severe perfusion/18F-FDG match (p < 0.001). High agreement (91%) for viability assessment between contrast-enhanced MRI and nuclear imaging was observed in segments without scar tissue on contrast-enhanced MRI as well as in segments with transmural scar tissue (83%). Of interest, disagreement was observed in segments with subendocardial scar tissue on contrast-enhanced MRI.ConclusionAgreement between contrast-enhanced MRI and nuclear imaging for assessment of viability was high in segments without scar tissue and in segments with transmural scar tissue on contrast-enhanced MRI. However, evident disagreement was observed in segments with subendocardial scar tissue on contrast-enhanced MRI, illustrating that the nonenhanced epicardial rim can contain either normal or ischaemically jeopardized myocardium.

Good correlation between gated single photon emission computed myocardial tomography and contrast ventriculography in the assessment of global and regional left ventricular function.

Purpose: The purpose of this study was to determine the reliability of the measured left ventricular ejection fraction (LVEF) and wall motion analysis by the recently introduced quantitative electrocardiographically (ECG)-gated myocardial perfusion single-photon emission computed myocardial tomography technique (gated SPECT) (QGS). Materials and methods: We compared technetium-99 m tetrofosmin gated SPECT imaging and contrast ventriculography in the assessment of global and regional left ventricular function in 74 patients with undiagnosed chest pain of whom 27 sustained a previous myocardial infarction. Results: Linear regression analysis demonstrated that gated SPECT determined LVEF correlated well with LVEF determined from contrast ventriculography (y = 0.95x + 1.9, r2 = 0.84, p < 0.0001). Bland–Altman plot analysis showed no systematic difference between the two sets of values derived from the two imaging approaches over a wide range of LVEF values. Exact agreement of segmental wall motion scores was 460 of 518 (89%) segments with a kappa value of 0.76 (p < 0.0001). Conclusion: We conclude that gated SPECT imaging is an accurate and reliable clinical tool to accurately measure global and regional left ventricular function.

Comparison of Multislice Computed Tomography to Gated Single-Photon Emission Computed Tomography for Imaging of Healed Myocardial Infarcts

The aim of the study was to evaluate the performance of multislice computed tomography (MSCT) for the detection and semiquantitative analysis of healed myocardial infarct in comparison to single-photon emission computed tomography (SPECT). Recently, MSCT was shown to allow detection of myocardial infarct by the presence of hypoenhanced areas. However, direct comparisons to other imaging modalities for infarct imaging were scarce. In 69 patients with healed myocardial infarct (>3 months), the presence of myocardial infarct and infarct score was assessed using SPECT and MSCT. In addition, regional and global left ventricular function was assessed using MSCT. In 62 of 69 patients (90%), a perfusion defect was detected using gated SPECT at rest. Using MSCT in these 62 patients (100%), hypoenhanced areas reflecting infarct were shown. In 3 of 7 patients (43%) without perfusion defects who underwent gated SPECT, MSCT identified regions of infarct. The infarct score on MSCT related well to the SPECT infarct score (12 +/- 10% vs 16 +/- 13%; r = 0.93, p <0.0001). In addition, good (inverse) correlations were shown for infarct score using MSCT and parameters of left ventricular function. In conclusion, healed myocardial infarct can be detected accurately using MSCT, with good correlation with SPECT.

Invasive Versus Noninvasive Evaluation of Coronary Artery Disease

OBJECTIVES We sought to compare the diagnostic information obtained from noninvasive characterization of coronary artery disease by using multidetector computed tomography (MDCT) and myocardial perfusion imaging (MPI) and to compare findings with the use of invasive coronary angiography and intravascular ultrasound (IVUS). BACKGROUND Preliminary comparisons have suggested that abnormal myocardial perfusion studies correlate well with significant luminal stenosis on MDCT coronary angiography. However, atherosclerotic coronary lesions may be detectable with the use of MDCT even in the presence of normal myocardial perfusion METHODS We performed MDCT, MPI, and conventional coronary angiography in 70 patients. In addition, IVUS was performed in 53 patients. Quantitative information was obtained from quantitative coronary angiography (QCA) and IVUS assessment of plaque burden and minimal luminal area. RESULTS Of 26 patients with an abnormal MPI study, 23 (88%) showed significant stenosis on MDCT. As compared with QCA, MDCT showed a sensitivity of 96% and specificity of 67% for the detection of stenoses > or =50% diameter narrowing in these patients. Mean diameter stenosis on QCA was 76% and mean minimal lumen area in IVUS was 3.3 mm(2). On the other hand, 27 (84%) of 44 patients with normal MPI had evidence of coronary atherosclerosis on MDCT (luminal stenosis > or =50%: n = 15, luminal stenosis <50%: n = 12, sensitivity of 100% and specificity of 83% as compared with QCA). Using IVUS, we found substantial plaque burden (mean 58.9 +/- 18.1% of cross-sectional area), but presence of a stenosis (minimal lumen area <4.0 mm(2)) in only 14 patients (mean minimal lumen area, 5.8 +/- 3.3 mm(2)). Only 7 patients with normal myocardial perfusion scans demonstrated absence of coronary atherosclerosis by MDCT. CONCLUSIONS Considerable plaque burden can be observed with MDCT even in the absence of myocardial perfusion abnormalities. This finding does not constitute a false-positive MDCT result, but rather reflects the fact that MDCT can detect atherosclerotic lesions that are not flow-limiting.