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Biomedical subjects

Paul Knaapen

Publications and source records attributed to Paul Knaapen.

17 recordsLinked to original sources

Antegrade dissection and re-entry vs retrograde strategy in chronic total occlusion percutaneous coronary intervention: Rationale and design of the ADRENALINE randomized study.

RATIONALE: While antegrade wiring (AW) is the most common initial strategy for chronic total occlusion (CTO) percutaneous coronary intervention (PCI), difficult CTO lesions frequently require either antegrade dissection and re-entry (ADR) or a retrograde strategy. Comparative data between ADR and the retrograde approach remain limited. DESIGN: The Antegrade Dissection vs Retrograde re-ENtry And Load of Interventionalist Effort (ADRENALINE) is a prospective, multicenter randomized study with a superiority design. It is planned to enroll 121 patients with difficult coronary CTO (J-CTO score ≥2) referred for CTO-PCI in accordance with the hybrid algorithm. Subjects undergoing successful AW will be included in the observational arm. Patients with failed or unattempted AW will be randomized 1:1 to ADR or retrograde CTO crossing strategy (n = 74). All patients will undergo pre- and postprocedural laboratory testing (including cardiac troponin T and creatine kinase-MB), cardiac magnetic resonance (CMR) for late gadolinium enhancement, and health status assessment by the Seattle Angina Questionnaire and the Rose Dyspnea Scale. The co-primary endpoints are total procedure time and successful guidewire crossing. Additionally, the relationship between different recanalization strategies and stress among interventional cardiologists will be explored. CONCLUSION: ADRENALINE is the first randomized study of ADR vs retrograde strategy for difficult CTO PCI, assessing procedural outcomes, CMR-detected myocardial infarction, and 3-month quality of life. ENROLMENT STATUS: The first patient was enrolled on July 29, 2025. As of June 14, 2026, 45 patients (26 randomized, 19 observational) of the planned 121 patients have been enrolled. TRIALS REGISTRATION: Clinicaltrials.gov: Identifier, NCT06878729.

Humans↗

FDG PET as a predictor of response to resynchronisation therapy in patients with ischaemic cardiomyopathy.

PURPOSE: Although resynchronisation therapy (CRT) is a promising addition to heart failure therapy, a substantial number of patients do not respond to CRT. As FDG PET has routinely been used for prediction of improvement after revascularisation in ischaemic cardiomyopathy, it was hypothesised that there is also a relationship between the extent of viable tissue and improvement as a result of CRT. METHODS: Thirty-nine patients with ischaemic cardiomyopathy (ejection fraction 27 +/- 9%) and a wide QRS complex underwent temporary pacing to determine the optimal pacing combination, i.e. that with the highest increase in cardiac index (CI) compared with baseline (measured by Doppler echocardiography). All patients also underwent FDG PET imaging. In 19 patients, CI measurements were repeated 10-12 weeks after permanent biventricular pacemaker implantation. RESULTS: Echocardiography (13-segment model) showed a mean of 9.8 +/- 1.6 dyssynergic segments, with preserved FDG uptake in 4.1 +/- 2.4 segments. CI improvement at the optimal pacing site was 20 +/- 9%. There was a linear relationship between the extent of viable tissue and CI improvement during pacing (p < 0.001). Using a cut-off value of more than three viable segments (ROC analysis), FDG PET had a sensitivity of 72% and a specificity of 71% for detection of the presence of haemodynamic improvement (i.e. a CI improvement >15%). The relation between CI improvement and viable tissue was similar at follow-up. CONCLUSION: A correlation was found between the extent of viable tissue and the haemodynamic response to CRT in patients with ischaemic cardiomyopathy, suggesting that FDG PET imaging may be useful to discriminate between responders and non-responders to CRT.

Aged↗

Quantification of myocardial perfusion using intravenous myocardial contrast echocardiography in healthy volunteers: comparison with positron emission tomography.

BACKGROUND: Intravenous myocardial contrast echocardiography (ivMCE) has the potential to evaluate myocardial contraction and perfusion simultaneously. The purpose of this study was to assess quantification of myocardial blood flow (MBF) using ivMCE and to compare this with MBF as measured with positron emission tomography (PET). METHODS: A total of 16 healthy volunteers underwent ivMCE using power pulse inversion and contrast agent microbubbles at rest and during pharmacologically induced vasodilation. Microbubble destruction was achieved with a burst of high-energy ultrasound, followed by imaging of contrast replenishment with low-energy ultrasound. Regions of interest were drawn and time intensity curves were calculated that were fitted to a monoexponential function. An estimate of MBF (perfusion estime) was calculated as the product of the plateau value A and the exponential beta describing the replenishment curve. MBF was measured with PET using oxygen-15-labeled water at rest and during adenosine stress. RESULTS: Significant correlations were found between MBF as measured with PET and perfusion estimate as measured with ivMCE in the left anterior descending coronary artery (r = 0.87, P < .01), right coronary artery (r = 0.66, P < .01), and left circumflex artery (r = 0.75, P < .01) territories. Heterogeneity, however, was significantly larger for ivMCE (coefficient of variation 32 +/- 15%) than for PET (9 +/- 6%) measurements (P < .01). CONCLUSION: Perfusion parameters as measured with ivMCE correlated with PET-derived MBF, but associated heterogeneity was significantly larger. Currently, this heterogeneity precludes true quantification of MBF using ivMCE.

Adult↗

Regional heterogeneity of resting perfusion in hypertrophic cardiomyopathy is related to delayed contrast enhancement but not to systolic function: a PET and MRI study.

BACKGROUND: Regional differences in resting myocardial blood flow (MBF) have been observed in patients with hypertrophic cardiomyopathy (HCM), but their determinants are currently unknown. This study verifies whether MBF at rest in HCM is related to delayed contrast enhancement (DCE) or regional systolic function (or both) as determined by magnetic resonance imaging. METHODS AND RESULTS: Fourteen patients with HCM were studied. MBF was measured with positron emission tomography by use of oxygen 15-labeled water. DCE and tissue tagging, to calculate end-systolic circumferential shortening (Ecc), were obtained with magnetic resonance imaging. The mean resting MBF was 0.78 +/- 0.19 mL x min(-1) x mL(-1), and there was a trend toward reduced MBF in the septum (0.72 +/- 0.11 mL x min(-1) x mL(-1)) compared with that in the lateral wall (0.84 +/- 0.29 mL x min(-1) x mL(-1)) (P = .092). The distribution patterns of DCE and Ecc were both heterogeneous, displaying significantly increased enhancement and impaired regional systolic function in the hypertrophic septum compared with the lateral wall (both P < .001). Resting MBF was inversely related to the extent of DCE (r = -0.30, P < .001), whereas MBF was not significantly related to Ecc (r = -0.15, P = .072). CONCLUSIONS: Regional heterogeneity of resting perfusion in HCM is related to the extent of DCE but not to regional systolic function.

Adult↗

Does myocardial fibrosis hinder contractile function and perfusion in idiopathic dilated cardiomyopathy? PET and MR imaging study.

PURPOSE: To prospectively evaluate, by using positron emission tomography (PET) and magnetic resonance (MR) imaging, the interrelationships between regional myocardial fibrosis, perfusion, and contractile function in patients with idiopathic dilated cardiomyopathy (DCM). MATERIALS AND METHODS: The study protocol was approved by the hospital ethics committee, and all subjects gave written informed consent. Sixteen patients with idiopathic DCM (mean age, 54 years +/- 11 [standard deviation]; nine men) and six healthy control subjects (mean age, 28 years +/- 2; five men) were examined with PET and MR tissue tagging. Oxygen 15-labeled water and carbon monoxide were used as tracers at PET to assess myocardial blood flow (MBF) and the perfusable tissue index (PTI), which is inversely related to fibrosis. MBF was determined at rest and during pharmacologically induced hyperemia. Maximum circumferential shortening (E(cc)) was determined with MR tissue tagging. Student t tests were performed for comparison of data sets, and linear regression was used to investigate the association between parameters. RESULTS: Mean global hyperemic MBF (2.23 mL/min/mL +/- 0.73), E(cc) (-10.5% +/- 2.9), and PTI (0.95 +/- 0.10) were lower in the patients with DCM than in the control subjects (4.33 mL/min/mL +/- 0.85, -17.4% +/- 0.6, and 1.09 +/- 0.12, respectively; P < .05 for all). In the patients with DCM, regional PTI was related to E(cc) (r = -0.21, P = .009) but not to resting or hyperemic MBF. Furthermore, regional E(cc) was correlated to both resting (r = -0.28, P = .004) and hyperemic MBF (r = -0.29, P < .001). In addition, the ratio of left ventricular end-diastolic volume to mass, as a reflection of wall stress, was related to global hyperemic MBF (r = -0.52, P = .047) and to global E(cc) (r = 0.69, P = .003). CONCLUSION: In idiopathic DCM, the extent of myocardial fibrosis is related to the impairment in contractile function, whereas fibrosis and perfusion do not seem to be interrelated. The degree of impairment of hyperemic myocardial perfusion is related to contractility and end-diastolic wall stress.

Adult↗

Propagation of onset and peak time of myocardial shortening in time of myocardial shortening in ischemic versus nonischemic cardiomyopathy: assessment by magnetic resonance imaging myocardial tagging.

OBJECTIVES: We aimed to study the relation between onset and peak time of circumferential shortening and the direction of propagation of these parameters in both ischemic and nonischemic patients. BACKGROUND: Peak time is often used to select patients for cardiac resynchronization therapy, whereas pacing influences only the onset times directly. Furthermore, it is unclear whether there is a consistent direction of propagation delay and whether this depends on the etiology. METHODS: Magnetic resonance imaging myocardial tagging with high temporal resolution (14 ms) was applied to 29 patients (18 nonischemic, 11 ischemic) and 17 healthy control subjects. Time to onset (T(onset)), to first peak (T(peak,first)), and to maximum peak (T(peak,max)) of circumferential shortening were determined. Three-dimensional vectors were calculated to denote the main direction of asynchrony. RESULTS: In both patient groups, T(onset) showed a significant positive relation with both T(peak,first) and T(peak,max); however, T(peak,first) correlated considerably better with T(onset) than did T(peak,max) (p < 0.0001 for nonischemic, and p < 0.01 for ischemic patients). Moreover, the relations between T(peak) and T(onset) were stronger in the nonischemic patients than in the ischemic patients (p < 0.001). In nonischemic patients, the propagation of T(onset) was consistently from septum to lateral wall. In the ischemic patients, however, no consistent direction of propagation was found. For both groups, the longitudinal propagation delays (between apex and base) were negligible compared with the short-axis delays. CONCLUSIONS: The relation between peak time and onset time of shortening is strongest in nonischemic patients and is most consistent when time to first peak is used (instead of time to maximum peak).

Aged↗

Delayed contrast enhancement and perfusable tissue index in hypertrophic cardiomyopathy: comparison between cardiac MRI and PET.

UNLABELLED: Delayed contrast enhancement (DCE) visualized by cardiac MRI (CMR) is a common feature in patients with hypertrophic cardiomyopathy (HCM), presumed to be related to myocardial fibrosis. The pathophysiologic basis of hyperenhancement in this patient group, however, remains unclear as limited histologic comparisons are available. The present study compares the perfusable tissue index (PTI), an alternative marker of myocardial fibrosis obtained by PET, with DCE-CMR in HCM. METHODS: Twenty-one patients with asymmetric septal HCM, 12 chronic myocardial infarction (MI) patients, and 6 age-matched healthy control subjects were studied with DCE-CMR and PET. PET was performed using (15)O-labeled water and carbon monoxide to obtain the PTI. RESULTS: No hyperenhancement was observed in control subjects and the PTI was within normal limits (1.10 +/- 0.07 [mean +/- SD]). In MI patients, the extent of hyperenhancement (25% +/- 16% [mean +/- SD]) was inversely related to the decrease in the PTI (0.94 +/- 0.12; r = -0.65, P < 0.05). Average hyperenhancement in HCM was 14% +/- 12%, predominantly located in the interventricular septum. The PTI in the hypertrophied interventricular septum, however, was not reduced (1.12 +/- 0.13). Furthermore, in contrast to MI patients, there was a modest positive correlation between the extent of DCE and the PTI in HCM (r = 0.45, P < 0.05). CONCLUSION: DCE in the hypertrophied septum of HCM patients is not accompanied by a decline in the PTI, and there is a positive correlation between the extent of DCE and the PTI. These results suggest that hyperenhancement may not be caused solely by fibrotic replacement scarring in this patient group. Other pathologic changes associated with HCM may also cause gadolinium-diethylenetriaminepentaacetic acid hyperenhancement.

Adult↗

Effects of cardiac resynchronization therapy on myocardial perfusion reserve.

BACKGROUND: Cardiac resynchronization therapy (CRT) is a relatively new treatment strategy for patients with heart failure and mechanical asynchrony. Reported effects of CRT on regional myocardial blood flow (MBF) are conflicting, and effects on hyperemic MBF are scarce. The aim of the present study was to assess serial changes of MBF and MBF reserve in patients receiving a biventricular pacemaker. METHODS AND RESULTS: Fourteen patients with heart failure (NYHA class III or IV; left ventricular ejection fraction <35%), QRS width >120 ms, and sinus rhythm were studied (mean age, 58+/-10 years; 8 men). MBF and hyperemic MBF were measured at baseline, 3 months after biventricular pacing (CRT on), and after cessation of pacing (CRT off) with PET and H2(15)O. CRT had no significant effect on resting MBF (baseline versus CRT on versus CRT off: 0.82+/-0.25 versus 0.69+/-0.24 versus 0.74+/-0.24 mL x min(-1) x mL(-1); P=NS). Hyperemic MBF increased during CRT (1.91+/-1.03 versus 2.66+/-1.66 versus 1.92+/-1.06 mL x min(-1) x mL(-1); P=0.01 by MANOVA), as did MBF reserve (2.25+/-1.00 versus 3.76+/-2.38 versus 2.49+/-0.94 mL x min(-1) x mL(-1); P=0.023). CRT (reversibly) resulted in a more homogeneous distribution of regional resting MBF as demonstrated by the septal-to-lateral ratio. The decrease in the ratio of left ventricular end-diastolic volume to left ventricular mass, as a reflection of wall stress, was related to the increase in hyperemic MBF (r=0.53, P<0.05). Left ventricular ejection fraction increased from 25+/-7% to 37+/-9% (P<0.01). CONCLUSIONS: Resting MBF is unaltered by CRT despite an increase in left ventricular function. However, the distribution pattern of resting MBF becomes more homogeneous. Hyperemic MBF and consequently MBF reserve are enhanced by CRT.

Aged↗

Postinjection transmission scanning in myocardial 18F-FDG PET studies using both filtered backprojection and iterative reconstruction.

UNLABELLED: The aim of the present study was to evaluate the effect of postinjection transmission scanning (Post-Tx) on both the qualitative interpretation and the quantitative analysis of cardiac (18)F-FDG PET images. Furthermore, the accuracy of 2 different methods to correct for emission contamination was studied. An additional aim of this study was to compare images reconstructed with both standard filtered backprojection (FBP) and an iterative reconstruction algorithm (ordered-subset maximization expectation [OSEM]). METHODS: Sixteen patients underwent dynamic (18)F-FDG imaging. Both before injection of (18)F-FDG and after completing the emission scan, a 10-min transmission scan was performed (Pre-Tx and Post-Tx, respectively). Images were reconstructed using both FBP and OSEM. The emission study reconstructed with Pre-Tx was considered to be the gold standard. Emission studies were also reconstructed with Post-Tx, with and without correction for emission contamination. Correction for emission contamination was performed with either transmission image segmentation (TIS) or by estimating the emission bias from the last emission frame (dwell profile [DP] method). All images were then compared by calculating ratios of (18)F-FDG activity between corresponding myocardial segments in each patient. Furthermore, qualitative grading of (18)F-FDG uptake was compared between the studies. RESULTS: The mean ratio of (18)F-FDG activity between segments from FBP-Post and FBP-Pre was 0.78 +/- 0.08. When TIS and DP were used, the mean ratios were 0.80 +/- 0.07 and 0.94 +/- 0.06, respectively. The use of OSEM resulted in, on average, 2% lower values for (18)F-FDG activity as compared with FBP. The mean normalized (18)F-FDG uptake was higher in FBP-Post, especially in segments with decreased (18)F-FDG activity. Only in the case of DP were no significant differences observed as compared with FBP-Pre. In general, qualitative analysis of the images showed that the agreement between the reconstruction methods was comparable with the reproducibility of FBP-Pre. CONCLUSION: Post-Tx for attenuation correction in cardiac (18)F-FDG PET scans resulted in substantial underestimation of (18)F-FDG activity. More accurate results were obtained with correction for emission contamination using DP. Differences in visual assessment of (18)F-FDG images were small. Finally, iterative reconstruction could be used as an alternative to FBP in static (18)F-FDG imaging of the heart.

Algorithms↗

Perfusable tissue index as a potential marker of fibrosis in patients with idiopathic dilated cardiomyopathy.

UNLABELLED: A varying degree of interstitial and perivascular fibrosis is a common finding in idiopathic dilated cardiomyopathy (DCM). The perfusable tissue index (PTI), obtained with PET, is a noninvasive tool for assessing myocardial fibrosis on a regional level. Measurements of the PTI in DCM, however, have not been performed yet. This study was undertaken to test the hypothesis that the PTI is reduced in patients with DCM. METHODS: Fifteen patients with an advanced stage of DCM (New York Heart Association class III or IV and left ventricular ejection fraction [LVEF] < 35%) and 11 healthy control subjects were studied. PET was performed using H(2)(15)O and C(15)O to obtain the perfusable tissue fraction (PTF) and the anatomic tissue fraction (ATF), respectively. RESULTS: The PTI (=PTF/ATF) was reduced in DCM compared with control subjects (0.91 +/- 0.12 vs. 1.12 +/- 0.10; P < 0.01). Heterogeneity of the PTI, expressed as the coefficient of variation, was increased in DCM versus that of healthy control subjects (0.18 +/- 0.07 vs. 0.13 +/- 0.06; P < 0.05). There was no correlation between the PTI and echocardiographically derived LVEF in both groups. CONCLUSION: The PTI was reduced in patients with an advanced stage of DCM. Interstitial and perivascular fibrosis may be responsible for this reduction. Furthermore, the degree of the PTI reduction was variable in DCM patients, both on a regional level and between patients. Noninvasive assessment of fibrosis with the PTI offers the opportunity to evaluate the effects of fibrosis on regional myocardial function, correlate fibrosis with prognosis, and monitor pharmaceutical intervention.

Adult↗

Evaluation of basis function and linear least squares methods for generating parametric blood flow images using 15O-water and Positron Emission Tomography.

PURPOSE: Parametric analysis of (15)O-water positron emission tomography (PET) studies allows determination of blood flow (BF), perfusable tissue fraction (PTF), and volume of distribution (V (d)) with high spatial resolution. In this paper the performance of basis function and linear least squares methods for generating parametric flow data were evaluated. PROCEDURES: Monte Carlo simulations were performed using typical perfusion values for brain, tumor, and heart. Clinical evaluation was performed using seven cerebral and 10 myocardial (15)O-water PET studies. Basis function (BFM), linear least squares (LLS), and generalized linear least squares (GLLS) methods were used to calculate BF, PTF, or V(d). RESULTS: Monte Carlo simulations and human studies showed that, for low BF values (<1 ml/min(-1)ml(-1), BF, PTF, and V(d) were calculated with accuracies better than 5% for all methods tested. For high BF (>2 ml/min(-1)ml(-1)), use of BFM provided more accurate V(d) compared with (G)LLS. CONCLUSIONS: In general, BFM provided the most accurate estimates of BF, PTF, and V(d).

Brain↗

Impact of scar on water-perfusable tissue index in chronic ischemic heart disease: Evaluation with PET and contrast-enhanced MRI.

BACKGROUND: The water-perfusable tissue index (PTI) is assumed to differentiate viable myocardium from scar tissue, but histological comparisons in humans are lacking. The present study compares PTI with delayed contrast-enhanced magnetic resonance imaging (DCE-MRI), a validated marker of fibrotic tissue, in patients with ischemic left ventricular (LV) dysfunction. In addition, the optimal PTI threshold for detection of myocardial viability was defined when DCE-MRI was taken as a reference. MATERIALS: Twenty patients with ischemic LV dysfunction were studied with positron emission tomography, using oxygen-15-labeled water and carbon monoxide as tracers, and DCE-MRI. RESULTS: Of the 200 analyzed segments, 112 demonstrated DCE and were subsequently divided in three subgroups according to the severity of enhancement. PTI was 1.04 +/- 0.21 in control segments and gradually decreased with increasing extent of DCE to 0.77 +/- 0.31 for segments with transmural enhancement (p < 0.001). However, PTI progressively underestimated infarct size with increasing quantities of scar tissue (r = 0.61, p < 0.01). A PTI cutoff value of 0.89 yielded the best diagnostic accuracy for detection of myocardial viability with sensitivity and specificity values of 75 and 77%, respectively. CONCLUSIONS: PTI is inversely related to the extent of scar tissue estimated by DCE-MRI in patients with chronic ischemic heart disease and LV dysfunction. However, with increasing quantities of scar tissue, PTI overestimates the extent of residual viable tissue. A PTI threshold of 0.89 yields the best diagnostic accuracy for viability detection.

Aged↗

Measurement of left ventricular volumes and function with O-15-labeled carbon monoxide gated positron emission tomography: comparison with magnetic resonance imaging.

BACKGROUND: Positron emission tomography (PET) with inhaled oxygen 15-labeled carbon monoxide (CO) is used as a marker of myocardial blood pool. Only a limited number of studies with small numbers of patients have reported on the assessment of left ventricular (LV) volumes by use of O-15-labeled CO. The aim of this study was to compare LV volumes and function as measured by routinely acquired blood pool images by use of gated O-15-labeled CO PET with the reference technique, cardiovascular magnetic resonance imaging (MRI). METHODS AND RESULTS: Thirty-four subjects with a varying degree of LV function were studied. LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), and LV ejection fraction (LVEF) were determined by both MRI and gated PET by use of O-15-labeled CO. Volumes were comparable with respect to LVEDV (196 +/- 83 and 192 +/- 91 mL, respectively; P = not significant). LVESV, however, was slightly overestimated by PET (119 +/- 85 and 136 +/- 94 mL, respectively; P < .05), resulting in a significant underestimation of LVEF (44% +/- 19% and 35% +/- 18%, respectively; P < .05). Observed correlations for LVEDV, LVESV, and LVEF were 0.90, 0.96, and 0.86, respectively (all P < .01). CONCLUSIONS: Gated O-15-labeled CO PET measurements of LVEDV, LVESV, and LVEF show good correlation with MRI over a wide range of LV volumes during routinely acquired blood pool images. LVEF, however, may be underestimated compared with MRI.

Adult↗