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ABSTRACT: Acute myocardial infarction leads to irreversible loss of cardiac myocytes, thereby diminishing the pump function of the heart. As a result, the strenuous workload imposed on the remaining cardiac myocytes often gives rise to subsequent cell loss until the vicious circle ends in chronic heart failure (CHF). Thus, we are in need of a therapy that could ameliorate or even reverse the disease progression of CHF. Endogenous regeneration of the mammalian heart has been shown in the neonatal heart, and the discovery that it may still persist in adulthood sparked hope for novel cardioregenerative therapies. As the basis for cardiomyocyte renewal, multipotent cardiac stem/progenitor cells (CSCs) that reside in the heart have been shown to differentiate into cardiac myocytes, smooth muscle cells, and vascular endothelial cells. These CSCs do have the potential to actively regenerate the heart but clearly fail to do so after abundant and segmental loss of cells, such as what occurs with myocardial infarction. Therefore, it is vital to continue research for the most optimal therapy based on the use or in situ stimulation of these CSCs. In this review, we discuss the current status of the cardioregenerative field. In particular, we summarize the current knowledge of CSCs as the regenerative substrate in the adult heart and their use in preclinical and clinical studies to repair the injured myocardium.
Stem cells translational medicine. 05/2013;
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JACC. Cardiovascular imaging 09/2012; 5(9):956-61. · 14.29 Impact Factor
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Tim P van de Hoef,
Froukje Nolte,
Peter Damman,
Ronak Delewi,
Matthijs Bax, Steven A J Chamuleau,
Michiel Voskuil,
Maria Siebes,
Jan G P Tijssen,
Jos A E Spaan,
Jan J Piek,
Martijn Meuwissen
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ABSTRACT: The assessment of functional coronary lesion severity using intracoronary physiological parameters such as coronary flow velocity reserve and the more widely used fractional flow reserve relies critically on the establishment of maximal hyperemia. We evaluated the diagnostic accuracy of the stenosis resistance index during nonhyperemic conditions, baseline stenosis resistance index, compared with established hyperemic intracoronary hemodynamic parameters, because achievement of hyperemia can be cumbersome in daily clinical practice.
A total of 232 patients, including 299 lesions (mean stenosis diameter 55%±11%), underwent myocardial perfusion scintigraphy for documentation of reversible perfusion defects. Distal coronary pressure and flow velocity were assessed with sensor-equipped guidewires during baseline and maximal hyperemia, induced by an intracoronary bolus of adenosine (20-40 µg). We determined stenosis resistance (SR) during baseline and hyperemic conditions as well as fractional flow reserve and coronary flow velocity reserve. The discriminative value for myocardial ischemia on myocardial perfusion scintigraphy of all parameters was compared using receiver-operating-characteristic curves. Baseline SR showed good agreement with myocardial perfusion scintigraphy. The diagnostic performance of baseline SR (area under the curve, 0.77; 95% CI, 0.71-0.83) was as accurate as fractional flow reserve and coronary flow velocity reserve (area under the curve, 0.77; 95% CI, 0.71-0.83 and area under the curve, 0.75; 95% CI, 0.68-0.81 respectively; P>0.05 compared with baseline SR for both). However, hyperemic SR, combining both pressure and flow velocity information during hyperemia, was superior to all other parameters (area under the curve, 0.81; 95% CI, 0.76-0.87; P<0.05 compared with all other parameters).
Combined pressure and flow velocity measurements during baseline conditions may provide a useful tool for functional lesion severity assessment without the need for potent vasodilators.
Circulation Cardiovascular Interventions 07/2012; 5(4):508-14. · 6.06 Impact Factor
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ABSTRACT: Cardiac regenerative therapy is still not used in daily clinical practice. A reason for this might be the modest effect on relevant global clinical endpoints [i.e. ejection fraction (EF)] in preclinical studies. To introduce proper improvement strategies, it is important to extend the focus from clinical endpoints to more detailed local measures of cardiac function. In this review, we discuss the measurement principles of all invasive and non-invasive techniques that are used to assess the local effects of cardiac regenerative therapy in order to improve feedback to researchers unravelling the dominant pathways that lead to effective cardiac regeneration. Generally adopted mechanisms of cardiac regenerative therapy are: (i) vasculogenesis, (ii) cardiomyogenesis, and (iii) matrix-assisted myocardium stabilization. Since direct in vivo measures of these mechanisms do not exist, we discuss the measurement techniques of local microvascular resistance, myocardial perfusion, viability, fibrosis, and deformation imaging. The ability of these techniques to reflect the mechanism of cardiac regenerative therapy, and the results of applications in stem cell studies are discussed, and critically commented upon. Special attention is given to applications of deformation imaging, since this has recently been suggested and used as a potential new technique to assess local changes of cardiac biomechanics, which requires special knowledge about cardiac physiology. We conclude that besides the clinically relevant EF measurements, detailed measures of local cardiac function provide information about the local changes induced by cardiac regenerative therapy. In particular, combination of deformation imaging, by ultrasound or magnetic resonance imaging, with simultaneously measured local geometry and pressure measurements is a promising approach to assess the effects of cardiac regenerative therapy on local cardiac biomechanics. This approach provides information about local tissue contractility, stiffness, and thereby remodelling. We recommend that researchers use this comprehensive approach in future studies.
European heart journal cardiovascular Imaging. 06/2012; 13(10):808-18.
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ABSTRACT: Patients with prosthetic heart valves may require assessment for coronary artery disease. We assessed whether valve artefacts hamper coronary artery assessment by multidetector CT.
ECG-gated or -triggered CT angiograms were selected from our PACS archive based on the presence of prosthetic heart valves. The best systolic and diastolic axial reconstructions were selected for coronary assessment. Each present coronary segment was scored for the presence of valve-related artefacts prohibiting coronary artery assessment. Scoring was performed in consensus by two observers.
Eighty-two CT angiograms were performed on a 64-slice (n = 27) or 256-slice (n = 55) multidetector CT. Eighty-nine valves and five annuloplasty rings were present. Forty-three out of 1160 (3.7%) present coronary artery segments were non-diagnostic due to valve artefacts (14/82 patients). Valve artefacts were located in right coronary artery (15/43; 35%), left anterior descending artery (2/43; 5%), circumflex artery (14/43; 32%) and marginal obtuse (12/43; 28%) segments. All cobalt-chrome containing valves caused artefacts prohibiting coronary assessment. Biological and titanium-containing valves did not cause artefacts except for three specific valve types.
Most commonly implanted prosthetic heart valves do not hamper coronary assessment on multidetector CT. Cobalt-chrome containing prosthetic heart valves preclude complete coronary artery assessment because of severe valve artefacts.
• Most commonly implanted prosthetic heart valves do not hamper coronary artery assessment • Prosthetic heart valve composition determines the occurrence of prosthetic heart valve-related artefacts • Björk-Shiley and Sorin tilting disc valves preclude diagnostic coronary artery segment assessment.
European Radiology 12/2011; 22(6):1278-86. · 3.22 Impact Factor
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ABSTRACT: Stem cell therapy is a treatment strategy for ischaemic heart disease patients. Meta-analysis of randomized human trials showed <5% improvement in left ventricular ejection fraction (LVEF). Meta-analysis of available pre-clinical data of ischaemic heart disease could provide important clues to design human clinical trials.
Random-effects meta-analysis was performed on pig, dog, or sheep studies investigating the effect of cardiac stem cell therapy in ischaemic cardiomyopathy (52 studies; n = 888 animals). Endpoints were LVEF and death. Ischaemia/reperfusion infarction was performed in 23 studies and chronic occlusion in 29 studies. Pooled analysis showed a LVEF difference of 7.5% at follow-up after cell therapy vs. control (95% confidence interval, 6.2-8.9%; P < 0.001). By exploratory multivariable meta-regression, significant predictors of LVEF improvement were: cell type [bone marrow mononuclear cells (BM-MNC) showed less effect than other cell types, e.g. mesenchymal stem cells; P = 0.040] and type of infarction (left anterior descending artery 8.0 vs. left circumflex artery 5.8%; P = 0.045). Cell therapy was not associated with increased mortality (P = 0.68). Sensitivity analysis showed trends towards more improvement with higher cell number (≥10(7)), chronic occlusion models, and late injections (>1 week). After follow-up of 8 weeks, the effect of cell therapy decreased to 6%.
This meta-analysis showed that large animal models are valid to predict the outcome of clinical trials. Our results showed that cell therapy is safe and leads to a preserved LVEF. Future trials should focus on cell types other than BM-MNC, large infarction, and strategies to obtain sustained effects.
Cardiovascular research 05/2011; 91(4):649-58. · 5.80 Impact Factor
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ABSTRACT: Heart failure is a major economic and public health problem. Despite the recent advances in drug therapy and coronary revascularization, the lost cardiomyocytes due to necrosis and apoptosis are not replaced by new myocardial tissue. Cell therapy is an interesting therapeutic option as it potentially improves contractility and restores regional ventricular function. Early clinical data demonstrated that cell transplantation, mainly delivered through non-surgical methods, is safe and feasible. However, several important issues need to be elucidated. This includes, next to determining the best cell type, the optimal delivery strategy, the biodistribution and the survival of implanted stem cells after transplantation. In this view, pre-clinical animal experiments are indispensable. Reporter genes, magnetic or radioactive labeling of stem cells have been developed to observe the fate and the distribution of transplanted cells using non-invasive imaging techniques. Several studies have demonstrated that these direct and non-direct labeling techniques may become an important tool in cell therapy. Integration of cell delivery and cell tracking will probably be a key for the success of cell therapy in patients. This review will provide a comprehensive overview on the various cell tracking and non-surgical cell delivery techniques, which are highly important in view of experimental and clinical studies.
The international journal of cardiovascular imaging 03/2011; 27(3):367-83. · 2.15 Impact Factor
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ABSTRACT: Infective endocarditis (IE) may lead to mycotic aortic root aneurysm formation. Herein is described the preoperative use of ECG-gated contrast-enhanced 256-slice cardiac computed tomography (CT) to optimize surgical planning by visualizing the location and extent of the mycotic aneurysm in two patients with complicated IE. In both cases, CT revealed a large aortic root mycotic aneurysm, accurately determined its location and extent, and also depicted the close relationship of the aneurysm to the major blood vessels. Intraoperative surgical findings corresponded to preoperative CT findings in both cases. Multislice CT is a valuable technique in patients with complicated IE that helps to optimize preoperative surgical planning.
The Journal of heart valve disease 09/2010; 19(5):623-5. · 0.81 Impact Factor
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Cardiovascular research 05/2009; 82(3):385-7. · 5.80 Impact Factor
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ABSTRACT: We evaluated deferral of PCI of intermediate coronary lesions (IL) using fractional (FFR) and coronary flow reserve (CFR) hyperemic stenosis resistance index (HSR) in patients with a negative or nondiagnostic and noninvasive stress tests.
Outcome after deferral of PCI of IL with discordant results between FFR and CFR is unknown.
PCI was deferred in 186 IL (mean diameter stenosis: 52%). Patients were divided according to the results of FFR and CFR in group A; FFR >or= 0.75 and CFR >or= 2.0 (n = 129), group B; FFR >or= 0.75 and CFR 2.0 (n = 28), group C; FFR 0.75 and CFR >or= 2.0 (n = 23) and group D; FFR 0.75 and CFR 2.0 (n = 6). Patients were followed for one year to document major adverse cardiac events (MACE).
Nineteen MACEs (0 deaths, 4 myocardial infarctions, 1 CABG, and 14 PCIs) occurred during a follow up of 323 +/- 88 days. MACE rate was lowest (4.7%) when FFR, CFR, and HSR were normal. A higher MACE rate was observed when concordant abnormal (group D) or discordant results between FFR and CFR (group B and C) were compared to concordant normal values (group A, 33.3% vs. 19.7% vs. 5.4%, P = 0.008). Multivariate regression analysis showed a higher predictive power for HSR than for FFR and CFR.
Abnormal FFR or abnormal CFR was documented in 31% of intermediate coronary lesions. Deferral of PCI in this group was associated with a high MACE rate, which underscores the rationale of combined pressure and flow measurements providing a stenosis resistance index that is better suited for clinical decision making in these lesions.
Catheterization and Cardiovascular Interventions 02/2008; 71(3):291-7. · 2.29 Impact Factor
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ABSTRACT: The aim of this study was to assess the influence of a second guidewire on the diagnostic accuracy of functional parameters of coronary lesion severity. Sixty-five patients with intermediate coronary lesions underwent myocardial perfusion scintigraphy. Fractional flow reserve (FFR), coronary flow velocity reserve (CFVR), and hyperemic stenosis resistance (HSR) index (HSR = stenosis pressure gradient / velocity) were determined in 77 lesions. Distal pressure and velocity were acquired simultaneously (dual wire) and sequentially (single wire) with two sensor-equipped guidewires. Overall, functional parameters deteriorated from single- to dual-wire assessment. In patients without ischemia, the good diagnostic performance of FFR, CFVR, and HSR deteriorated significantly (P < 0.001) when assessed by dual wires, with an increase in the number of false-positive results. This trend was more pronounced for HSR, since the presence of a second wire reduced maximal velocity and increased the pressure gradient. The presence of two guidewires, especially across a myocardial perfusion scintigraphy-induced nonsignificant lesion, is associated with overestimation of the hemodynamically assessed lesion severity and, therefore, is likely to have a major impact on clinical decision making. This underscores the advantage of a dual-sensor-equipped guidewire for the evaluation of stenosis severity by combined pressure and velocity measurements.
AJP Heart and Circulatory Physiology 06/2007; 292(5):H2349-55. · 3.71 Impact Factor
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Steven A J Chamuleau
Nature Clinical Practice Cardiovascular Medicine 07/2005; 2(6):282-3. · 7.04 Impact Factor
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ABSTRACT: Homogeneity of microvascular resistance in different perfusion areas of the same heart is generally assumed. We investigated the effect of the severity of an epicardial stenosis on microvascular resistance in 27 patients with coronary artery disease and stable angina. All patients had an angiographically normal coronary artery, an artery with an intermediate lesion, and an artery with a severe lesion; the latter was treated with angioplasty. In each patient, distal blood flow velocity and pressure were measured during baseline and maximal hyperemia (induced by intracoronary adenosine) using a Doppler and pressure guide wire, respectively. The ratio of mean distal pressure to average peak blood flow velocity was used as an index for the microvascular resistance (MRv). Within patients, the hyperemic MRv was higher in arteries with more severe stenosis (P = 0.021). After percutaneous transluminal coronary angioplasty (PTCA), the hyperemic MRv decreased (pre-PTCA, 2.6 vs. post-PTCA, 1.9 mmHg.cm(-1)s(-1), P < 0.01) toward the value of the reference artery (1.7 mmHg.cm(-1)s(-1); P = 0.67). We conclude that there is a positive association between coronary lesion severity and variability of distal microvascular resistance that normalizes after angioplasty. This study challenges the concept of uniform distribution of hyperemic MRv that is relevant for the interpretation of both noninvasive and invasive diagnostic tests.
AJP Heart and Circulatory Physiology 11/2003; 285(5):H2194-200. · 3.71 Impact Factor
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Martijn Meuwissen,
Robbert J de Winter, Steven A J Chamuleau,
Mechteld Heijne,
Karel T Koch,
Anja van den Berg,
Jan P van Straalen,
Matthijs Bax,
Carl E Schorborgh,
Dermot Kearney,
Gerard T Sanders,
Jan G P Tijssen,
Jan J Piek
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ABSTRACT: This study is the first that combines a serum marker of inflammation (C-reactive protein) and intracoronary-derived fractional flow reserve. A low C-reactive protein level was strongly associated with uncomplicated follow-up in patients with hemodynamic nonsignificant coronary lesions. These results show that C-reactive protein provides additional information relevant for clinical decision-making in patients with intermediate (30% to 70%) coronary lesions.
The American Journal of Cardiology 10/2003; 92(6):702-5. · 3.37 Impact Factor
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ABSTRACT: Adequate patient selection for percutaneous coronary intervention is of utmost importance to minimize early and late complications. Consequently, objective evidence for myocardial ischemia is mandatory for the management of patients with coronary artery disease, in particular in multivessel disease and intermediate lesions (40-70% diameter stenosis on angiography). The use of sensor-equipped guide wires for the assessment of functional coronary lesion severity has become widespread in the catheterization laboratory. The indices derived from pressure or flow measurements, fractional flow reserve, coronary flow velocity reserve and relative coronary flow velocity reserve show a high agreement with noninvasive stress testing. However, while these indices are based on either intracoronary pressure or flow, they do not investigate the hemodynamics of the coronary circulation entirely, leading to ambiguous outcomes. Only the use of simultaneously measured pressure and flow will avoid any possible misinterpretation of the data.
Expert Review of Cardiovascular Therapy 10/2003; 1(3):471-9.
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ABSTRACT: Patients with unstable coronary syndromes often have complex morphology of coronary stenoses at angiography. We evaluated the association between qualitative assessment of coronary stenoses and plaque inflammation determined by immunohistochemistry.
A total of 79 patients with unstable (n = 46) or stable angina (n = 33) underwent directional coronary atherectomy for culprit lesions. Qualitative analysis of coronary angiograms was performed using a modified Ambrose classification. Coronary lesions were categorized as either simple (concentric and eccentric type I, n = 29) or complex (eccentric type II and multiple irregularities, n = 50). Cryostat sections of retrieved atherosclerotic specimens were stained immunohistochemically with monoclonal antibodies, alpha-actin (smooth muscle cells), CD68 (macrophages), and CD3 (T lymphocytes). The extent of atherosclerotic inflammation within each coronary lesion was determined by the percentage of immunopositive macrophages per total tissue area (including smooth muscle cells) and the number of T lymphocytes per mm(2).
The mean (+/- SD) percentage of macrophages in atherectomy specimens from patients with unstable angina was greater than in specimens from patients with stable angina (21% +/- 14% vs. 13% +/- 10%, P = 0.01); similar results were seen when complex coronary lesions were compared with simple lesions (23% +/- 13% vs. 9% +/- 8%, P <0.001). In multivariate linear regression models, the combination of unstable angina and lesion complexity was strongly associated with the percentage of plaque macrophages.
The extent of atherosclerotic plaque inflammation is associated with angiographic grading of coronary lesion complexity and unstable angina.
The American Journal of Medicine 06/2003; 114(7):521-7. · 5.43 Impact Factor
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ABSTRACT: Pressure-based fractional flow reserve (FFR) is used clinically to evaluate the functional severity of a coronary stenosis, by predicting relative maximal coronary flow (Q(s)/Q(n)). It is considered to be independent of hemodynamic conditions, which seems unlikely because stenosis resistance is flow dependent. Using a resistive model of an epicardial stenosis (0-80% diameter reduction) in series with the coronary microcirculation at maximal vasodilation, we evaluated FFR for changes in coronary microvascular resistance (R(cor) = 0.2-0.6 mmHg. ml(-1). min), aortic pressure (P(a) = 70-130 mmHg), and coronary outflow pressure (P(b) = 0-15 mmHg). For a given stenosis, FFR increased with decreasing P(a) or increasing R(cor). The sensitivity of FFR to these hemodynamic changes was highest for stenoses of intermediate severity. For P(b) > 0, FFR progressively exceeded Q(s)/Q(n) with increasing stenosis severity unless P(b) was included in the calculation of FFR. Although the P(b)-corrected FFR equaled Q(s)/Q(n) for a given stenosis, both parameters remained equally dependent on hemodynamic conditions, through their direct relationship to both stenosis and coronary resistance.
AJP Heart and Circulatory Physiology 10/2002; 283(4):H1462-70. · 3.71 Impact Factor
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ABSTRACT: BACKGROUND: Both coronary blood flow velocity reserve (CFVR) and myocardial fractional flow reserve (FFR) are used to evaluate the hemodynamic severity of coronary lesions. However, discordant results between CFVR and FFR have been observed in 25% to 30% of intermediate coronary lesions. An index of stenosis resistance based on a combination of intracoronary pressure and flow velocity may improve the assessment of functional coronary lesion severity. METHODS AND RESULTS: Single photon emission computed tomography (SPECT) was performed in 151 patients with angina to determine reversible perfusion defects within one-week before cardiac catheterization. Coronary pressure and flow velocity was measured distal to 181 single coronary lesions with a mean diameter stenosis of 56% (range: 32% to 85%). Maximum hyperemia was induced by 15 to 20 microg IC adenosine to determine CFVR, FFR, and the hyperemic stenosis resistance index (h-SRv), defined as the ratio of hyperemic stenosis pressure gradient (mean aorta pressure-mean distal pressure) and hyperemic average peak-flow velocity. Receiver-operating-characteristic curves of CFVR, FFR, and h-SRv were calculated to evaluate the predictive value for presence of reversible perfusion defects on SPECT with the use of the area under curve (AUC). The AUC was significantly higher for h-SRv (0.90+/-0.03) compared with those for CFVR (0.80+/-0.04; P=0.024) and FFR (0.82+/-0.03; P=0.018), respectively. Agreement with SPECT was particularly higher (73%) than for CFVR (49%, P=0.022) or FFR (51%, P=0.037) in the group of lesions showing discordant results between CFVR and FFR CONCLUSION: These results indicate that hyperemic stenosis resistance index is a more powerful predictor of reversible perfusion defects than CFVR or FFR.
Circulation 08/2002; 106(4):441-6. · 14.74 Impact Factor
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ABSTRACT: Vascular diseases, like peripheral arterial diseases (PAD) and coronary artery disease (CAD), are common diseases with a high morbidity. We investigated and compared the impact of these diseases on daily life using health-related quality of life (HRQOL) analysis. In 89 patients with PAD and 89 patients with multivessel CAD, the SF-36 was assessed before diagnostic staging and compared with an age-matched reference population. Both groups of patients had a significantly impaired HRQOL as compared to a reference population. Patients with PAD scored significantly (p < 0.001) lower than those with CAD on the domains general health perception, change in health, physical functioning, social functioning, and pain. Patients with PAD have a reduced HRQOL in comparison with patients with CAD. Each disease has an impact on a specific domain of the HRQOL. Vascular disease mainly influences physical health.
Annals of Vascular Surgery 07/2002; 16(4):495-500. · 1.03 Impact Factor
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Steven A J Chamuleau,
Rene A Tio,
Carel C de Cock,
Ebo D de Muinck,
Nico H J Pijls,
Berthe L F van Eck-Smit,
Karel T Koch,
Martijn Meuwissen,
Marcel G W Dijkgraaf,
Angelina de Jong,
Hein J Verberne,
Rob A M van Liebergen,
Gert Jan Laarman,
Jan G P Tijssen,
Jan J Piek
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ABSTRACT: This study aimed to investigate the roles of intracoronary derived coronary flow velocity reserve (CFVR) and myocardial perfusion scintigraphy (single photon emission computed tomography, or SPECT) for management of an intermediate lesion in patients with multivessel coronary artery disease.
Evaluation of the functional significance of intermediate coronary narrowings (40% to 70% diameter stenosis) is important for clinical decision making and risk stratification.
In a prospective, multicenter study, SPECT was performed in 191 patients with stable angina and multivessel disease and scheduled for angioplasty (percutaneous transluminal coronary angioplasty, or PTCA) of a severe coronary narrowing. Coronary flow velocity reserve was determined selectively distal to an intermediate lesion in another artery using a Doppler guidewire. Percutaneous transluminal coronary angioplasty of the intermediate lesion was deferred when SPECT was negative or CFVR greater-than-or-equal 2.0. Patients were followed for one year to document major cardiac events (death, infarction, revascularization), related to the intermediate lesion.
Reversible perfusion defects were documented in the area of the intermediate lesion in 30 (16%) patients; CFVR was positive in 46 (24%) patients. Percutaneous transluminal coronary angioplasty of the intermediate lesion was deferred in 182 patients. During follow-up, 19 events occurred (3 myocardial infarctions, 16 revascularizations). Coronary flow velocity reserve was a more accurate predictor of cardiac events than was SPECT; relative risk: CFVR 3.9 (1.7 to 9.1), p < 0.05; SPECT 0.5 (0.1 to 3.2), p = NS. Multivariate analysis revealed CFVR as the only significant predictor for cardiac events.
Deferral of PTCA of intermediate lesions in multivessel disease is safe when CFVR greater-than-or-equal 2.0 (event rate 6%). This selective evaluation of coronary lesion severity during cardiac catheterization allows a more accurate risk stratification than does SPECT, which is important for clinical decision making in this patient cohort.
Journal of the American College of Cardiology 04/2002; 39(5):852-8. · 14.16 Impact Factor
