Marcel P. M. Stokkel

Prognostic value of multislice computed tomography and gated single-photon emission computed tomography in patients with suspected coronary artery disease.

OBJECTIVES This study was designed to determine whether multislice computed tomography (MSCT) coronary angiography has incremental prognostic value over single-photon emission computed tomography myocardial perfusion imaging (MPI) in patients with suspected coronary artery disease (CAD). BACKGROUND Although MSCT is used for the detection of CAD in addition to MPI, its incremental prognostic value is unclear. METHODS In 541 patients (59% male, age 59 +/- 11 years) referred for further cardiac evaluation, both MSCT and MPI were performed. The following events were recorded: all-cause death, nonfatal infarction, and unstable angina requiring revascularization. RESULTS In the 517 (96%) patients with an interpretable MSCT, significant CAD (MSCT > or =50% stenosis) was detected in 158 (31%) patients, and abnormal perfusion (summed stress score [SSS]: > or =4) was observed in 168 (33%) patients. During follow-up (median 672 days; 25th, 75th percentile: 420, 896), an event occurred in 23 (5.2%) patients. After correction for baseline characteristics in a multivariate model, MSCT emerged as an independent predictor of events with an incremental prognostic value to MPI. The annualized hard event rate (all-cause mortality and nonfatal infarction) in patients with none or mild CAD (MSCT <50% stenosis) was 1.8% versus 4.8% in patients with significant CAD (MSCT > or =50% stenosis). A normal MPI (SSS <4) and abnormal MPI (SSS > or =4) were associated with an annualized hard event rate of 1.1% and 3.8%, respectively. Both MSCT and MPI were synergistic, and combined use resulted in significantly improved prediction (log-rank test p value <0.005). CONCLUSIONS MSCT is an independent predictor of events and provides incremental prognostic value to MPI. Combined anatomical and functional assessment may allow improved risk stratification.

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.

Beneficial effects of sorafenib on tumor progression, but not on radioiodine uptake, in patients with differentiated thyroid carcinoma.

OBJECTIVE Treatment options for patients with radioactive iodine (RaI) refractory metastases of differentiated thyroid carcinoma (DTC) are limited. We studied the effects of the multitarget tyrosine kinase inhibitor sorafenib on the reinduction of RaI uptake and tumor progression. DESIGN Open, single center, single arm 26-week prospective phase II study with open-ended extension. METHODS We treated 31 patients with progressive metastatic or locally advanced RaI refractory DTC with sorafenib 400 mg b.i.d. The primary endpoint was reinduction of RaI uptake at 26 weeks. Additional endpoints were the radiological response and the influence of bone metastases. RESULTS At 26 weeks of sorafenib therapy, no reinduction of RaI uptake at metastatic sites was observed, but 19 patients (59%) had a clinical beneficial response, eight of whom had a partial response (25%) and 11 had stable disease (34%). Seven patients had progressive disease (22%). Sorafenib was significantly less effective in patients with bone metastases. The estimated median progression free survival was 58 weeks (95% confidence interval, CI, 47-68). In general, thyroglobulin (Tg) response (both unstimulated and TSH stimulated) reflected radiological responses. The median time of the nadir of Tg levels was 3 months. Responses were not influenced by histological subtype, mutational status or other variables. No unusual side effects were observed. CONCLUSIONS Sorafenib has a beneficial effect on tumor progression in patients with metastatic DTC, but was less effective in patients with bone metastases. Diagnostic whole body scintigraphy did not reveal an effect of sorafenib on the reinduction of RaI uptake.

Preoperative Evaluation of Patients With Primary Head and Neck Cancer Using Dual-Head 18Fluorodeoxyglucose Positron Emission Tomography

OBJECTIVE To evaluate the value of 18fluorodeoxyglucose (FDG) positron emission tomography (PET) in primary head and neck cancer. BACKGROUND DATA Head and neck carcinomas tend to metastasize to regional lymph nodes rather than to spread hematogenously. With nodal metastases, cure rates decrease by approximately 50%. Moreover, in approximately 3% of the patients, a second primary tumor is found at initial presentation. METHODS Fifty-four consecutive patients (31 men and 23 women; mean age 60 years, range 34-81 years) with previously untreated squamous cell carcinomas of the oral cavity or oropharynx were studied. Before surgery and within a period of 3 weeks, clinical examination, chest x-ray, computed tomography (CT), ultrasonography with fine-needle aspiration cytology (US/ FNAC), and FDG-PET were performed. All study results were scored per neck side and were also classified as 0 (no metastases), 1 (single metastasis), or 2 (multiple metastases). RESULTS The sensitivity for the detection of lymph node metastases per neck side was 96%, 85%, and 64% for FDG-PET, CT, and US/FNAC, respectively. The specificity was 90%, 86%, and 100% for FDG-PET, CT, and US/FNAC, respectively. In terms of the classification, FDG-PET showed the best correlation with the histologic data. Finally, in nine patients (17%), a second primary tumor was detected by FDG-PET and confirmed by histologic evaluation. CONCLUSION Because of the high prevalence of second primary tumors detected by FDG-PET and the decreased error rate in the assessment of lymph node involvement compared with CT and US, FDG-PET should be routinely performed in patients with primary head and neck cancer.

Effects of low-iodide diet on postsurgical radioiodide ablation therapy in patients with differentiated thyroid carcinoma

objective Most patients with differentiated thyroid carcinoma (DTC) undergo total thyroidectomy followed by routine radioiodide thyroid remnant ablation. Most centres that routinely perform radioiodide ablation prescribe a low‐iodide diet (LID) to increase the radioiodide accumulation in thyroid remnants. The efficacy of an LID on thyroid remnant ablation, however, has never been demonstrated convincingly.

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.

Serum thyroglobulin concentrations predict disease‐free remission and death in differentiated thyroid carcinoma

Objective  Most studies on the diagnostic value of serum thyroglobulin (Tg) concentrations in differentiated thyroid carcinoma (DTC) use fixed cut‐off levels in heterogeneous groups of patients with respect to initial therapy and do not provide prognostic data. The objective was to investigate the prognostic values of serum Tg for disease‐free remission and death, measured at fixed time‐points after initial therapy using receiver operator characteristic (ROC) curve analyses.

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.