Design and rationale of the NetherLands registry of invasive Coronary vasomotor Function Testing (NL-CFT).

BACKGROUND: Angina without angiographic evidence of obstructive coronary artery disease (ANOCA) is a highly prevalent condition with insufficient pathophysiological knowledge and lack of evidence-based medical therapies. This affects ANOCA patients prognosis, their healthcare utilization and quality of life. In current guidelines, performing a coronary function test (CFT) is recommended to identify a specific vasomotor dysfunction endotype. The NetherLands registry of invasive Coronary vasomotor Function testing (NL-CFT) has been designed to collect data on ANOCA patients undergoing CFT in the Netherlands. METHODS: The NL-CFT is a web-based, prospective, observational registry including all consecutive ANOCA patients undergoing clinically indicated CFT in participating centers throughout the Netherlands. Data on medical history, procedural data and (patient reported) outcomes are gathered. The implementation of a common CFT protocol in all participating hospitals promotes an equal diagnostic strategy and ensures representation of the entire ANOCA population. A CFT is performed after ruling out obstructive coronary artery disease. It comprises of both acetylcholine vasoreactivity testing as well as bolus thermodilution assessment of microvascular function. Optionally, continuous thermodilution or Doppler flow measurements can be performed. Participating centers can perform research using own data, or pooled data will be made available upon specific request via a secure digital research environment, after approval of a steering committee. CONCLUSION: NL-CFT will be an important registry by enabling both observational and registry based (randomized) clinical trials in ANOCA patients undergoing CFT.

Implantable defibrillator therapy and mortality in patients with non-ischaemic dilated cardiomyopathy : An updated meta-analysis and effect on Dutch clinical practice by the Task Force of the Dutch Society of Cardiology.

BACKGROUND: Primary prophylactic implantable cardioverter-defibrillators (ICDs) in patients with non-ischaemic cardiomyopathy (NICMP) remains controversial. This study sought to assess the benefit of ICD therapy with or without cardiac resynchronisation therapy (CRT) in patients with NICMP. In addition, data were compared with real-world clinical data to perform a risk/benefit analysis. METHODS: Relevant randomised clinical trials (RCTs) published in meta-analyses since DANISH, and in PubMed, EMBASE and Cochrane databases from 2016 to 2020 were identified. The benefit of ICD therapy stratified by CRT use was assessed using random effects meta-analysis techniques. RESULTS: Six RCTs were included in the meta-analysis. Among patients without CRT, ICD use was associated with a 24% reduction in mortality (hazard ratio [HR]: 0.76; 95% confidence interval [CI]: 0.62-0.93; P = 0.008). In contrast, among patients with CRT, a CRT-defibrillator was not associated with reduced mortality (HR: 0.74, 95% CI 0.47-1.16; P = 0.19). For ICD therapy without CRT, absolute risk reduction at 3­years follow-up was 3.7% yielding a number needed to treat of 27. CONCLUSION: ICD use significantly improved survival among patients with NICMP who are not eligible for CRT. Considering CRT, the addition of defibrillator therapy was not significantly associated with mortality benefit compared with CRT pacemaker.

URGENT 1.5: diagnostic accuracy of the modified HEART score, with fingerstick point-of-care troponin testing, in ruling out acute coronary syndrome.

BACKGROUND: The HEART score is a validated risk stratification tool for chest pain patients presenting to the emergency department and was recently investigated for implementation in a pre-hospital setting. Fingerstick (capillary blood) point-of-care (POC) troponin testing enables quick measurements outside the hospital and seems easier to implement than the current venous blood sampling techniques. This study investigates the diagnostic accuracy of the modified HEART score, integrating fingerstick POC troponin testing, in ruling out acute coronary syndrome (ACS). METHODS: The data of 96 patients with chest pain, included in a study investigating a novel POC troponin device under development at the cardiac emergency department, were analysed retrospectively. Based on the patients' admission data and capillary POC high-sensitivity troponin I (hs-cTnI) results, the modified HEART score was determined. The outcome measure, for evaluating the diagnostic accuracy of the modified HEART score, was the occurrence of ACS. RESULTS: Of the total study population, 33 patients (34%) were diagnosed with ACS. Seventeen patients (18%) were classified as low risk (0-3 points) and one patient (6%) in this group was diagnosed with ACS. The sensitivity and negative predictive value of the modified HEART score was 97.0 and 97.6%, respectively. CONCLUSION: The modified HEART score, integrating capillary POC hs-cTnI results, is a promising tool for ruling out ACS in patients with chest pain presenting to the cardiac emergency department. These results encourage prospective investigation into the integration of fingerstick POC troponin testing in the modified HEART score in a pre-hospital setting.

Ischaemia with no obstructive coronary arteries.

Ischaemia with no obstructive coronary arteries (INOCA) is a common ischaemic heart disease with a female preponderance, mostly due to underlying coronary vascular dysfunction comprising coronary microvascular dysfunction and/or epicardial coronary vasospasm. Since standard ischaemia detection tests and coronary angiograms are not suitable to diagnose coronary vascular dysfunction, INOCA is often overlooked in current cardiology practice. Future research, including large outcome trials, is much awaited. Yet, adequate diagnosis is possible and treatment options are available and vital to reduce symptoms and most probably improve cardiovascular prognosis. This review intends to give a brief overview of the clinical presentation, underlying pathophysiology, and the diagnostic and treatment options in patients with suspected INOCA.

Off-site primary percutaneous coronary intervention in a new centre is safe: comparing clinical outcomes with a hospital with surgical backup.

OBJECTIVES: To evaluate the procedural and clinical outcomes of a new primary percutaneous coronary intervention (PPCI) centre without surgical back-up (off-site PCI) and to investigate whether these results are comparable with a high volume on-site PCI centre in the Netherlands. BACKGROUND: Controversy remains about the safety and efficacy of PPCI in off-site PCI centres. METHODS: We retrospectively analysed clinical and procedural data as well as 6­month follow-up of 226 patients diagnosed with ST-elevated myocardial infarction (STEMI) who underwent PPCI at VieCuri Medical Centre Venlo and 115 STEMI patients who underwent PPCI at Catharina Hospital Eindhoven. RESULTS: PPCI patients in VieCuri Medical Centre had similar procedural and clinical outcomes to those in Catharina Hospital. Overall there were no significant differences. The occurrence of procedural complications was low in both groups (8.4 % VieCuri vs. 12.3 % Catharina Hospital). In the VieCuri group there was one procedural-related death. No patients in either group needed emergency surgery. At 30 days, 17 (7.9 %) patients in the VieCuri group and 9 (8.1 %) in the Catharina Hospital group had a major adverse cardiac event. CONCLUSION: Performing PPCI in an off-site PCI centre is safe and effective. The study results show that the procedural and clinical outcomes of an off-site PPCI centre are comparable with an on-site high-volume PPCI centre.

Delays in the treatment of patients with acute coronary syndrome: Focus on pre-hospital delays and non-ST-elevated myocardial infarction.

Delays in patients suspected of acute coronary syndrome (ACS) should be kept as short as possible to reduce complications and mortality. In this review we discuss the substantial pre-hospital delays of ST-elevated myocardial infarction (STEMI) patients as well as non-STEMI patients. The pre-hospital delays include patient, doctor and emergency medical transport (EMT) delay. Patient delay is among the longest in the pre-hospital chain of ACS patients. Interventions as mass media campaigns or individual education programs have not yet shown much improvement. Patients with chest pain most often contact the general practitioner (GP) instead of the recommended EMT, increasing delays as well. To decrease the delays by referring all patients promptly and without restriction to the emergency department (ED) is not feasible. Up to 80% of the patients with chest pain do not have a cardiac diagnosis and thus referral of all these patients would result in overcrowding of the ED. Triage is therefore crucial. Triage of patients with chest pain is therefore imperative and there is a great need of (validated) triage tools.

The first year of the Venlo percutaneous coronary intervention program: procedural and 6-month clinical outcomes.

OBJECTIVES: Analysis of the first results of off-site percutaneous coronary interventions (PCI) and fractional flow reserve (FFR) measurements at VieCuri Medical Centre for Northern Limburg in Venlo. BACKGROUND: Off-site PCI is accepted in the European and American Cardiac Guidelines as the need for PCI increases and it has been proven to be a safe treatment option for acute coronary syndrome. METHODS: Retrospective cohort study reporting characteristics, PCI and FFR specifications, complications and 6-month follow-up for all consecutive patients from the beginning of off-site PCI in Venlo until July 2012. If possible, the data were compared with those of Medical Centre Alkmaar, the first off-site PCI centre in the Netherlands. RESULTS: Of the 333 patients, 19 (5.7 %) had a procedural complication. At 6 months, a major adverse cardiovascular event (MACE) occurred in 43 (13.1 %) patients. There were no deaths or emergency surgery related to the PCI or FFR procedures. There was no significant difference in occurrence of a MACE or adverse cerebral event between the Alkmaar and Venlo population in the 30-day follow-up. CONCLUSION: This study demonstrates off-site PCI at VieCuri Venlo to have a high success rate. Furthermore, there was a low complication rate, low MACE and no procedure-related mortality.

Cardiac magnetic resonance imaging in daily practice in a peripheral medical centre: description of the first 383 patients.

BACKGROUND: Cardiac magnetic resonance (CMR) imaging has evolved over the last decade into an indispensable diagnostic instrument. CMR imaging noninvasively provides structural, functional and morphological information with high spatial resolution and an unlimited field of view. Since October 2006 the VieCuri Medical Centre in Venlo has a CMR scanner at its disposal. OBJECTIVES: The goal of this study was to analyse the impact of CMR imaging on diagnosis and treatment in daily practice in the setting of a medium-volume peripheral hospital. METHODS: All patients who underwent CMR imaging between October 2006 and November 2008 were included in this analysis. The medical history before and after the CMR scan, the application form for CMR imaging and the outcome of the scans were reviewed. CMR images, obtained using a 1.5-T magnetic resonance imaging system, were reviewed by a multidisciplinary team. RESULTS: In 235 patients CMR imaging demonstrated one or more abnormalities, whereas CMR imaging did not identify any abnormalities in 148 patients. CMR imaging confirmed an expected finding in 166 cases, identified an unexpected condition in 69 cases, ruled out an expected finding in 59 cases and ruled out a suspected condition in 89 cases. Due to better insight into diagnosis, CMR imaging resulted in a change of treatment in 166 of the total of 383 CMR scans (43%). CONCLUSION: In a relevant number of cases CMR imaging leads to a change in the treatment of a patient, proving the value of CMR imaging as a diagnostic modality. Therefore, CMR imaging is an excellent opportunity for peripheral medical centres to improve efficiency and the standard of patient care. (Neth Heart J 2010;18:524-30.).

Dronedarone in patients with atrial fibrillation.

Dronedarone is a recently developed new class III antiarrhythmic drug which possesses electrophysiological properties of all four Vaughan-Williams classes. An important difference with amiodarone is that it does not contain an iodine component and therefore lacks the iodine-related adverse effects. Based on currently available data, dronedarone can not be recommended as first-line therapy for either rhythm or rate control. We recommend to initiate rhythm or rate control with drugs as indicated in the 2006 guidelines of the ESC and other organisations. As amiodarone, dronedarone can be given to patients for whom standard drug therapy is not effective, or limited by (severe) side effects, although it is less effective than amiodarone. Nevertheless, it may be considered to give dronedarone initially to patients who would otherwise have received amiodarone, since the latter has more severe side effects than the former drug. The daily dosage of dronedarone is oral administration, 400 mg twice daily. Dronedarone is contraindicated in patients with impaired left ventricular function (NYHA class III/IV) and haemodynamic instability. (Neth Heart J 2010;18:370-3.).

Campylobacter jejuni: enterocolitis and myopericarditis.

Campylobacter jejuni enteritis is the commonest enteric infection in the developed world. There are only few reported cases in the medical literature of cardiac complications associated with C. jejuni enterocolitis, most of the patients in the reported literature were males and most of the cases followed a benign course. Severe left ventricular dysfunction complicated only two cases of C. jejuni myocarditis. We report here a young male with Campylobacter myopericarditis. We believe that this is the first reported case of Campylobacter associated myopericarditis in The Netherlands. The mechanism by which Campylobacter causes myo(peri)carditis remains uncertain, it may be caused by direct bacterial invasion of cardiac tissue, bacterial toxins, circulating immune complexes, or cytotoxic T-cells. Since the number of C. jejuni infection is increasing worldwide, cardiac complications, although rare, are a remarkable manifestation of this pathogen and should be always kept in mind.

Purulent pericarditis, an uncommon entity in modern practice: a case report.

We report an 82-year-old female with pneumococcal pneumonia. Antimicrobial therapy was started in an early stage of the disease. On the 10th day of admission she developed peripheral pitting oedema with elevated jugular venous pressure and a drop in blood pressure. Her electrocardiogram showed sinus tachycardia and concave upward ST-segment elevation in almost all leads. A transthoracic two-dimensional echocardiogram revealed a large circumferential pericardial effusion, with diastolic collapse of the right atrium and a mitral inflow pattern that suggested cardiac tamponade. Emergency pericardiocentesis was performed, releasing 600 cc of thick green purulent material, followed by good haemodynamic recovery. The haemodynamic state, pneumonic infiltrate and inflammatory parameters responded gradually to antimicrobial therapy and the patient recovered and was discharged after six weeks. We conclude that even susceptible strains of Streptococcus pneumonia in a patient with no predisposing factors may still cause purulent pericarditis, even in the era of adequate antibiotic therapy.

Safety and feasibility of prehospital thrombolysis in combination with active rescue PCI strategy for acute ST-elevation myocardial infarction.

BACKGROUND/OBJECTIVES: The purpose of this observational study was to provide an impression of the outcomes of prehospital thrombolysis in combination with an active coronary angioplasty intervention (PCI) strategy for acute ST-elevation myocardial infarction. METHODS: In a group of 151 consecutive patients the following parameters were measured: time delay, percentage of reperfusion, reocclusion, stroke, death, need for PCI and the number of protocol violations. RESULTS: The diagnosis by the ambulance paramedics was made in 8±6 minutes, followed by thrombolysis in 13±7 minutes (median±SD). In 2% (3) of the patients the thrombolytic agent was erroneously administered without complications. The elapsed time from onset of symptoms to treatment was a median of 112±77 minutes. Five percent (7) of the patients died in the first 30 days and 2% (3) suffered an intracerebral haemorrhage. Reperfusion was documented in 76% (112) of the patients, from which 18% (20) reoccluded in the following 24 hours. In patients where reperfusion was not established or reocclusion occurred, patients underwent rescue/facilitated PCI: in total 37% (55 patients). After three months 9% (13) of the patients had severly impaired (EF <40%) left ventricular function. CONCLUSION: In our region, we successfully implemented the prehospital thrombolysis system achieving a competitive call-to-needle time and reperfusion rate. The percentage of patients who violated the protocol, suffered an intracerebral haemorrhage, died and/or had severely impaired left ventricular function was acceptable.

Effectiveness of a physiotherapeutic exercise programme for chronic heart failure patients.

BACKGROUND: This pilot study was conducted to evaluate the design and effects of a physiotherapeutic exercise programme on exercise capacity, muscle strength and quality of life in patients with chronic heart failure. METHODS: Eighteen patients with chronic heart failure were randomly assigned to either a training group (n=9) participating in a physiotherapeutic exercise programme or a regular care control group (n=9). At baseline and after three months patients underwent a maximal bicycle test, a six-minute walk test, a respiratory test, three muscle strength tests and a number of questionnaires pertaining to quality of life. RESULTS: Compared with the control group, a positive trend in the results of the training group was found. All measures showed a greater increase in the intervention group than in the control group. In five measures the difference was significant: 1. distance covered during the six-minute walk test (p=.036), 2. Borg rating of perceived exertion after this walk test (p=.006), 3. 'care and housekeeping' of the activities daily life questionnaire (p=.004), 4. 'symptoms' (p=.048) and 5. 'quality of life' (p=.040) of the Kansas City Cardiomyopathy Questionnaire. CONCLUSION: The study in chronic heart failure patients suggests both that the design of our training programme is workable and that our physiotherapeutic exercises produce positive effects. Further research with more patients is necessary to generalise these results to the population of patients with stable chronic heart failure. To assess the long-term effects of the programme, follow-up research is necessary.

A mathematical model for the heterogeneity of myocardial perfusion using nitrogen-13-ammonia.

UNLABELLED: Heterogeneity of left ventricular myocardial perfusion is an important clinical characteristic. Different aspects of this heterogeneity were analyzed. METHODS: The coefficient of variation (v), characterizing heterogeneity, was modeled as a function of the number of segments (n), characterizing spatial resolution of the measurement, using two independent pairs of mutually dependent parameters: the first pair describes v as a power function of n, and the second pair adds a correction for n small. n was varied by joining equal numbers of neighboring segments. Local similarity of the perfusion was characterized by the correlation between the perfusions of neighboring segments. Genesis of the perfusion distribution was modeled by repeated asymmetric subdivision of the perfusion into a volume among two equal subvolumes. These analyses were applied to study the differences between 16 syndrome X patients and 16 age- and sex-matched healthy volunteers using 13N-ammonia parametric PET perfusion data with a spatial resolution of 480 segments. RESULTS: The heterogeneity of patients is higher for the whole range of spatial resolutions considered (2 < or = n < or = 480; for n = 480, v = 0.22 +/- 0.03 and 0.18 +/- 0.02; p < 0.005). This is because the first pair of parameters differs between patients and volunteers (p < 0.005), whereas the second pair does not (p > 0.1). For both groups of subjects there is a significant positive local correlation for distances up to 30 segments. This correlation is a formal description of the patchy nature of the perfusion distribution. CONCLUSION: When comparing values of v, these should be based on the same value of n. The model makes it possible to calculate v for all values of n < or = 480. Mean perfusion together with the two pairs of parameters are necessary and sufficient to describe all aspects of the perfusion distribution. For n small, heterogeneity estimation is less reliable. Patients have a higher heterogeneity because their perfusion distribution is more asymmetrical from the third to the seventh generation of subdivision (8 < or = n < or = 128). Therefore, a spatial resolution of n > or = 128 is recommended for parametric imaging of perfusion with PET. Patients have only a very slightly more patchy distribution than volunteers. The differences in perfusion between areas with low perfusion and areas with high perfusion is larger in patients.

Comparison of thallium scintigraphy and positron emission tomography.

Assessment of tissue viability has become an important issue in recent years. Scintigraphic measurements have provided important diagnostic, therapeutic, and prognostic information in patients with myocardial dysfunction, who may improve in left ventricular function after revascularization. For detection of regional myocardial ischemia and viability, thallium 201 (201Tl) has been the most widely used tracer in single-photon scintigraphy. However, 201Tl scintigraphy may underestimate regional viability, especially after myocardial infarction. Positron emission tomography (PET) provides an advanced imaging technology that permits the accurate definition of regional tracer distribution. In combination with nitrogen (13N) ammonia, PET allows for the sensitive and specific detection of coronary artery disease. Several studies indicate the superiority of this approach in comparison with standard 201Tl tomographic (SPECT) imaging. In addition, regional blood flow can be accurately measured with 13N ammonia PET, and this approach can be employed in conjunction with pharmacologic stress imaging to quantify regional flow reserve. In combination with metabolic markers, such as fluorine 18 (18F) deoxyglucose, an indicator of glucose uptake, PET is capable of assessing myocardial viability. Furthermore, the PET approach may differentiate between various forms of cardiomyopathy. More studies are needed to define the cost-benefit ratio of both the 201Tl reinjection and the PET technique for the management of patients with coronary artery disease or cardiomyopathy.

Coronary vasomotion in patients with syndrome X: evaluation with positron emission tomography and parametric myocardial perfusion imaging.

The aim of this study was to elucidate further the causative mechanism of abnormal coronary vasomotion in patients with syndrome X. In patients with syndrome X, defined as angina pectoris and documented myocardial ischaemia during stress testing with normal findings at coronary angiography, abnormal coronary vasomotion of either the micro- or the macrocirculation has been suggested as the causative mechanism. Accordingly, we evaluated endothelial function, vasodilator reserve, and perfusion heterogeneity in these patients. Twenty-five patients with syndrome X (definitely normal coronary arteriogram, group A), 15 patients with minimal coronary artery disease (group B) and 21 healthy volunteers underwent [13N]ammonia positron emission tomography at rest, during cold pressor stimulation (endothelial function) and during dipyridamole stress testing (vasodilator reserve). Heterogeneity of myocardial perfusion was analysed by parametric polar mapping using a 480-segment model. In both patient groups, resting perfusion was increased compared to the normal subjects: group A, 127+/-31 ml.min-1.100 g-1; group B, 124+/-30 ml.min-1.100 g-1 normal subjects, 105+/-21 ml.min-1.100 g-1 (groups A and B vs normals, P<0.05). These differences were abolished after correction for rate-pressure product. During cold pressor stimulation, the perfusion responses (ratio of cold pressor perfusion to resting perfusion) were similar among the patients and the control subjects (group A, 1.20+/-0.23; group B, 1.24+/-0.22; normal subjects, 1.23+/-0.14). Likewise, during dipyridamole stress testing, perfusion responses were similar among the three groups (group A, 2.71+/-0.67; group B, 2.77+/-1.29; normal subjects, 2. 91+/-1.04). In group A the heterogeneity of resting perfusion, expressed as coefficient of variation, was significantly different from the volunteers (20.1+/-4.5 vs 17.0+/-3.0, P<0.05). In group B (coefficient of variation 19.4+/-3.9) the difference from normal volunteers was not significant. In this study, patients with syndrome X and patients with minimal coronary artery disease showed normal perfusion responses during cold pressor stimulation and dipyridamole stress testing. Our findings therefore suggest that endothelial dysfunction and impaired vasodilator reserve are of no major pathophysiological relevance in patients with syndrome X. Rather, other mechanisms such as increased sympathetic tone and focal release of vasoactive substances may play a role in the pathogenesis of syndrome X.

Long-term cigarette smoking is associated with increased myocardial perfusion heterogeneity assessed by positron emission tomography.

The pathophysiology of smoking-related coronary events in patients with normal coronary arteries is incompletely understood. This study was conducted to explore, in subjects without symptoms of cardiovascular disease, the long-term effects of smoking on regional coronary artery vasoactivity, especially during sympathetic stimulation. In ten smoking and ten non-smoking sex- and age-matched healthy volunteers, segmental myocardial perfusion was studied using dynamic parametric nitrogen-13 ammonia positron emission tomography at rest and during sympathetic stimulation evoked by the cold pressor stimulation. Smokers demonstrated a higher myocardial perfusion at rest (116+/-17 ml/min/100 g vs 96+/-20 ml/min/100 g, P <0.01) and an impaired myocardial perfusion increase during cold pressor stimulation (1.02+/-0.15 vs 1.18+/-0.17, P <0.05). The heterogeneity of perfusion, expressed as coefficient of variation, was significantly different between the smoking and the non-smoking group. The coefficient of variation of segmental myocardial perfusion was higher in smokers at rest (17.5%+/-4.2% vs 13.5%+/-1. 9%, P <0.05) and during cold pressor stimulation (17.0%+/-3.2% vs 13. 9%+/-1.8%, P <0.05). We conclude that the long-term effects of smoking in healthy volunteers are associated with (1) increased myocardial perfusion at rest, (2) impaired myocardial perfusion response to cold pressor stimulation, and (3) increased myocardial perfusion heterogeneity both at rest and during cold pressor stimulation. These results may suggest that in healthy subjects the long-term effect of smoking is related to abnormal coronary artery vasoactivity, presumably induced by an interplay of regional endothelial dysfunction and autonomic dysregulation.

Comparison between positron emission tomography myocardial perfusion imaging and intracoronary Doppler flow velocity measurements at rest and during cold pressor testing in angiographically normal coronary arteries in patients with one-vessel coronary artery disease.

With use of invasive methods, coronary endothelial function is generally studied by examining the response of epicardial coronary arteries to intracoronary administered acetylcholine or to cold pressor testing. Because invasive methods have substantial inherent limitations, studies should attempt to evaluate coronary endothelial function noninvasively. This study examines a noninvasive technique for endothelium-related coronary stress testing. In myocardial regions supplied by nonstenotic coronary arteries, we compared positron emission tomography (PET) myocardial perfusion imaging with intracoronary Doppler flow velocity measurements during endothelium-related stress testing. PET perfusion was examined at rest and during cold pressor testing in 10 patients with 1-vessel coronary artery disease. In nonstenotic coronary arteries, flow velocity measurements were obtained at rest, during cold pressor testing, and during intracoronary administered acetylcholine. Perfusion and flow velocity responses and stress/rest ratios were compared between the techniques during the various circumstances. Positive correlations were found between: (1) cold pressor Doppler flow velocity responses and acetylcholine Doppler flow velocity responses (r = 0.84, SEE = 0.19, p = 0.003); (2) cold pressor PET perfusion responses and cold pressor Doppler flow velocity responses (r = 0.70, SEE = 0.17, p = 0.02); and (3) cold pressor PET perfusion responses and acetylcholine Doppler flow velocity responses (r = 0.62, SEE = 0.19, p = 0.05). These results suggest that in angiographically normal coronary arteries, both the flow velocity and the perfusion responses during cold pressor testing may be related to the response to acetylcholine.