Effectiveness of an intervention to reduce sedentary behaviour as a personalised secondary prevention strategy for patients with coronary artery disease: main outcomes of the SIT LESS randomised clinical trial.

BACKGROUND: A high sedentary time is associated with increased mortality risk. Previous studies indicate that replacement of sedentary time with light- and moderate-to-vigorous physical activity attenuates the risk for adverse outcomes and improves cardiovascular risk factors. Patients with cardiovascular disease are more sedentary compared to the general population, while daily time spent sedentary remains high following contemporary cardiac rehabilitation programmes. This clinical trial investigated the effectiveness of a sedentary behaviour intervention as a personalised secondary prevention strategy (SIT LESS) on changes in sedentary time among patients with coronary artery disease participating in cardiac rehabilitation. METHODS: Patients were randomised to usual care (n = 104) or SIT LESS (n = 108). Both groups received a comprehensive 12-week centre-based cardiac rehabilitation programme with face-to-face consultations and supervised exercise sessions, whereas SIT LESS participants additionally received a 12-week, nurse-delivered, hybrid behaviour change intervention in combination with a pocket-worn activity tracker connected to a smartphone application to continuously monitor sedentary time. Primary outcome was the change in device-based sedentary time between pre- to post-rehabilitation. Changes in sedentary time characteristics (prevalence of prolonged sedentary bouts and proportion of patients with sedentary time ≥ 9.5 h/day); time spent in light-intensity and moderate-to-vigorous physical activity; step count; quality of life; competencies for self-management; and cardiovascular risk score were assessed as secondary outcomes. RESULTS: Patients (77% male) were 63 ± 10 years and primarily diagnosed with myocardial infarction (78%). Sedentary time decreased in SIT LESS (- 1.6 [- 2.1 to - 1.1] hours/day) and controls (- 1.2 [ ─1.7 to - 0.8]), but between group differences did not reach statistical significance (─0.4 [─1.0 to 0.3]) hours/day). The post-rehabilitation proportion of patients with a sedentary time above the upper limit of normal (≥ 9.5 h/day) was significantly lower in SIT LESS versus controls (48% versus 72%, baseline-adjusted odds-ratio 0.4 (0.2-0.8)). No differences were observed in the other predefined secondary outcomes. CONCLUSIONS: Among patients with coronary artery disease participating in cardiac rehabilitation, SIT LESS did not induce significantly greater reductions in sedentary time compared to controls, but delivery was feasible and a reduced odds of a sedentary time ≥ 9.5 h/day was observed. TRIAL REGISTRATION: Netherlands Trial Register: NL9263. Outcomes of the SIT LESS trial: changes in device-based sedentary time from pre-to post-cardiac rehabilitation (control group) and cardiac rehabilitation + SIT LESS (intervention group). SIT LESS reduced the odds of patients having a sedentary time >9.5 hours/day (upper limit of normal), although the absolute decrease in sedentary time did not significantly differ from controls. SIT LESS appears to be feasible, acceptable and potentially beneficial, but a larger cluster randomised trial is warranted to provide a more accurate estimate of its effects on sedentary time and clinical outcomes. CR: cardiac rehabilitation.

Sedentary Behaviour Intervention as a Personalised Secondary Prevention Strategy (SIT LESS) for patients with coronary artery disease participating in cardiac rehabilitation: rationale and design of the SIT LESS randomised clinical trial.

Patients with coronary artery disease (CAD) are more sedentary compared with the general population, but contemporary cardiac rehabilitation (CR) programmes do not specifically target sedentary behaviour (SB). We developed a 12-week, hybrid (centre-based+home-based) Sedentary behaviour IntervenTion as a personaLisEd Secondary prevention Strategy (SIT LESS). The SIT LESS programme is tailored to the needs of patients with CAD, using evidence-based behavioural change methods and an activity tracker connected to an online dashboard to enable self-monitoring and remote coaching. Following the intervention mapping principles, we first identified determinants of SB from literature to adapt theory-based methods and practical applications to target SB and then evaluated the intervention in advisory board meetings with patients and nurse specialists. This resulted in four core components of SIT LESS: (1) patient education, (2) goal setting, (3) motivational interviewing with coping planning, and (4) (tele)monitoring using a pocket-worn activity tracker connected to a smartphone application and providing vibrotactile feedback after prolonged sedentary bouts. We hypothesise that adding SIT LESS to contemporary CR will reduce SB in patients with CAD to a greater extent compared with usual care. Therefore, 212 patients with CAD will be recruited from two Dutch hospitals and randomised to CR (control) or CR+SIT LESS (intervention). Patients will be assessed prior to, immediately after and 3 months after CR. The primary comparison relates to the pre-CR versus post-CR difference in SB (objectively assessed in min/day) between the control and intervention groups. Secondary outcomes include between-group differences in SB characteristics (eg, number of sedentary bouts); change in SB 3 months after CR; changes in light-intensity and moderate-to-vigorous-intensity physical activity; quality of life; and patients' competencies for self-management. Outcomes of the SIT LESS randomised clinical trial will provide novel insight into the effectiveness of a structured, hybrid and personalised behaviour change intervention to attenuate SB in patients with CAD participating in CR. Trial registration number NL9263.

Safety and long-term effects of renal denervation: Rationale and design of the Dutch registry.

BACKGROUND: Percutaneous renal denervation (RDN) has recently been introduced as a treatment for therapy-resistant hypertension. Also, it has been suggested that RDN may be beneficial for other conditions characterised by increased sympathetic nerve activity. There are still many uncertainties with regard to efficacy, safety, predictors for success and long-term effects. To answer these important questions, we initiated a Dutch RDN registry aiming to collect data from all RDN procedures performed in the Netherlands. METHODS: The Dutch RDN registry is an ongoing investigator-initiated, prospective, multicentre cohort study. Twenty-six Dutch hospitals agreed to participate in this registry. All patients who undergo RDN, regardless of the clinical indication or device that is used, will be included. Data are currently being collected on eligibility and screening, treatment and follow-up. RESULTS: Procedures have been performed since August 2010. At present, data from 306 patients have been entered into the database. The main indication for RDN was hypertension (n = 302, 99%). Patients had a mean office blood pressure of 177/100 (±29/16) mmHg with a median use of three (range 0-8) blood pressure lowering drugs. Mean 24-hour blood pressure before RDN was 157/93 (±18/13) mmHg. RDN was performed with different devices, with the Simplicity™ catheter currently used most frequently. CONCLUSION: Here we report on the rationale and design of the Dutch RDN registry. Enrolment in this investigator-initiated study is ongoing. We present baseline characteristics of the first 306 participants.

Acute myocardial infarction due to coronary artery embolism in a patient with atrial fibrillation.

A 66-year-old female was referred for primary coronary intervention because of acute inferior STelevation myocardial infarction. Electrocardiography also showed atrial fibrillation. Coronary angiography showed a distal occlusion of the right coronary artery. Two different wires did not pass the occlusion, but dislodged the apparent thrombus more distally. No abnormalities were seen in the course of the recanalised part of the vessel. The sequential angiographic images together with the presence of atrial fibrillation are highly suggestive of coronary embolism as the cause of the myocardial infarction. Anticoagulation and rate control strategy was initiated. The patient was discharged in good condition. (Neth Heart J 2009;17:297-9.).

Outcome and quality of life one year after percutaneous coronary interventions in octogenarians.

BACKGROUND: While percutaneous coronary intervention (PCI) is increasingly being performed in octogenarians, little is known about the quality of life (QOL) one year after PCI. We assessed the one-year outcome and QOL after PCI. METHODS: Outcome and QOL at one year were assessed in patients of 80 years and older who underwent PCI at our institution. We used the RAND-36 Health Survey to assess health-related QOL at follow-up. The EuroSCORE was used for reference risk assessment. RESULTS: Ninety-eight patients (mean age 82.7+/-2.9 years; 60% female) underwent PCI. Acute PCI was performed in 36% of the patients. Canadian Cardiovascular Society (CCS) angina class before the procedure was class III for 28% and class IV for 64%. Of the patients, 98% were in the highest-risk group (additive EuroSCORE 6+). The overall PCI success rate was 94%. Mortality at one year was 19% (38% acute vs. 12% elective PCI). At followup, general health was rated as fairly good and better then before PCI (CCS I and II: 77%). RAND-36 scores for the mental component were better than scores for the physical component. Physical functioning (41+/-28) and role limitations caused by physical health problems (32+/-37) had the worst scores. The mental component vitality had the lowest (55+/-20) and mental health the highest (70+/-21) score. Social functioning was in general good (67+/-26). CONCLUSION: Octogenarians have a high mortality risk following PCI, especially in acute PCI. In survivors QOL is acceptable with a better mental than physical score. In general, PCI in octogenarians has a positive effect on health perception, with less symptoms of angina pectoris. (Neth Heart J 2008;16:117-22.).

Measurement of leg blood pressure: the most straightforward way to the diagnosis.

Two adult patients with presumed primary hypertension are presented. In the first patient the diagnosis of coarctation of the aorta was straightforward while in the second patient there was a substantial delay in reaching the correct diagnosis. A 32-year-old patient was analysed for hypertension in the outpatient clinic. At physical examination a systolic cardiac murmur was present and leg blood pressure was not measurable. Magnetic resonance imaging angiography showed a severe coarctation of the thoracic aorta with extensive distended collateral blood vessels. A second patient was a 31-year-old man referred with longstanding hypertension and an unsatisfactory blood pressure response to treatment. Previously, a diagnosis of primary hypertension was made. Renal computed tomography angiography excluded renal artery stenosis as a cause of hypertension but disclosed many distended collateral blood vessels in the musculus rectus abdominis and in the upper abdominal area. Leg blood pressure was measured and further analysis revealed a coarctation of the aorta. Both patients illustrate and emphasise the importance of leg blood pressure measurement at a first analysis of adult hypertensive patients and should always be performed when hypertension is accompanied by murmurs or weak femoral pulsations.

Bone marrow cell therapy after acute myocardial infarction: the HEBE trial in perspective, first results.

During the last decennium, the role of bone marrow mononuclear cells (BMMC) has been underscored in the healing process after acute myocardial infarction (AMI). Although these cells improve left ventricular recovery after AMI in experimental studies, results from large-scale randomised trials investigating BMMC therapy in patients with AMI have shown contradictory results. To address this issue the HEBE study was designed, a multicentre, randomised trial, evaluating the effects of intracoronary infusion of BMMCs and the effects of intracoronary infusion of peripheral blood mononuclear cells after primary percutaneous coronary intervention. The primary endpoint of the HEBE trial is the change in regional myocardial function in dysfunctional segments at four months relative to baseline, based on segmental analysis as measured by magnetic resonance imaging. The results from the HEBE trial will provide detailed information about the effects of intracoronary BMMC therapy on post-infarct left ventricular recovery. In addition, further analysis of the data and material obtained may provide important mechanistic insights into the contribution of BMMCs to natural recovery from AMI as well as the response to cell therapy. This may significantly contribute to the development of improved cell-based therapies, aiming at optimising post-infarct recovery and preventing heart failure. (Neth Heart J 2008;16:436-9.).

[Antithrombotic therapy during percutaneous coronary interventions]. / Antitrombotische therapie rondom percutane coronaire interventie.

Antithrombotic therapy is essential during percutaneous coronary interventions for the prevention of peri-procedural death and myocardial infarction. The most commonly used agents are aspirin, clopidogrel and heparin in patients treated by percutaneous angioplasty or receiving an arterial stent. Glycoprotein IIb/IIIa receptor antagonists such as abciximab are indicated during percutaneous interventions in high-risk-patients as well as, in principle, in all patients with an acute coronary syndrome with ST-segment elevation undergoing primary percutaneous angioplasty. In patients with so-called drug-eluting stents, clopidogrel should be continued for several months longer than the usual 30 days.

Lower body positive pressure by anti-G garment inflation: a suitable method to increase pulmonary capillary wedge pressure in healthy elderly subjects.

In a study on non-invasive assessment of pulmonary capillary wedge pressure (PCWP), we sought a method to increase PCWP non-invasively. We hypothesized that inflation of an anti-G garment was suitable to increase PCWP non-invasively in healthy elderly subjects. In 20 subjects, aged 70 +/- 4 years (mean +/- SD), before, immediately after, and 4 min after anti-G garment inflation to 52 mmHg, PCWP and mean pulmonary artery pressure (MPAP) were measured with a Swan-Ganz catheter, and mean arterial blood pressure (MAP) with Finapres, in supine and semi-recumbent position. Supine, PCWP (mmHg, mean +/- SD) increased from 9.9 +/- 2.1 to 15.5 +/- 3.9** immediately after inflation and 13.4 +/- 3.7** at 4 min; semi-recumbent from 8.9 +/- 2.0 to 17.5 +/- 3.3** and 14.7 +/- 2.9** (*P<0.05, **P< 0.001 versus before inflation). MPAP (mmHg) increased after inflation: supine 16.9 +/- 2.3 to 22.3 +/- 4.6** and 20.6 +/- 3.9** and semi-recumbent 15.7 +/- 2.8 to 24.3 +/- 5.1** and 22.5 +/- 3.5**, suggesting that increased preload was the primary effect of anti-G garment inflation. Supine MAP (mmHg) increased from 96.0 +/- 11.3 to 101.4 +/- 13.4** and 100.5 +/- 12.7* and semi-recumbent from 102.0 +/- 8.9 to 108.3 +/- 11.4** and 106.0 +/- 11.3*, suggesting an effect of increased afterload as well. The latter was supported by an increase in total peripheral resistance (d s cm(-5)) from 1346 +/- 299 to 1441 +/- 384 after 4 min (P = 0.057) and from 1461 +/- 341 to 1532 +/- 406 (P = 0.054), supine and semi-recumbent respectively, while cardiac output remained unchanged. Complications did not occur. We conclude that in healthy elderly subjects, anti-G garment inflation is a safe, non-invasive, method to induce a significant increase in PCWP. Our findings justify its application in future studies in which non-invasive temporary increase in PCWP is required.

Dutch guidelines for interventional cardiology: institutional and operator competence and requirements for training.

Interventional cardiology is an expanding field within cardiovascular medicine and today it is generally accepted that cardiologists require specific training, knowledge and skills. Hospitals where coronary interventions are performed must be properly equipped and able to provide specialised care. Percutaneous coronary interventions are frequently used for coronary revascularisation. The public should have confidence in the uniformity of high quality care. Therefore, such quality of care should be maintained by certification of the individual operators, general guidelines for institutional requirements and formal audits. The Netherlands Society of Cardiology (NVVC) will be implementing a new registration system for cardiologists with a subspecialisation that will include registration for interventional cardiology. The NVVC asked the Working Group of Interventional Cardiology (WIC) to update the 1994 Dutch guidelines on operator and institutional competence, and requirements for training in interventional cardiology in order to incorporate them into the official directives. The present guidelines represent the expert opinion of the Dutch interventional cardiology community and are in accordance with international regulations. After two rounds of discussion, the NVVC approved the guidelines in November 2004 during the autumn meeting.

Fibrinolysis and primary PCI for ST-elevation myocardial infarction: call for a more refined perspective.

The latest meta-analysis comparing fibrinolysis with primary percutaneous intervention (PCI) has fuelled the discussion regarding the best reperfusion therapy for acute ST-elevation myocardial infarction. As far as patients presenting to centres with intervention facilities are concerned, the superiority of primary PCI has been unequivocally demonstrated. However, only a small proportion of patients with St-elevation myocardial infarction primarily present to an intervention centre, the majority go to a hospital without these facilities. The optimal reperfusion strategy for patients presenting to a nonintervention centre or for patients presenting in the prehospital setting has been studied less extensively and the question remains as to whether all these patients should be transferred to an intervention centre to undergo primary PCI. The available data to date on interhospital transport for primary PCI do show a mortality benefit for primary PCI. Yet, as far as inferences to clinical practice are concerned, it remains to be seen whether these studies are truly representative: almost half of patients in the transportation trials received streptokinase, they were treated relatively late, and the subsequent revascularisation strategy was rather conservative. The impact of primary PCI as compared with prehospital fibrinolysis in patients presenting in the prehospital setting has so far only been addressed in the randomised CAPTIM trial, without significant differences in outcome. Additional studies are warranted, with early treatment as primary focus. For patients presenting to non-intervention centres or prehospitally, the impact of triage, and of combined pharmaco-invasive reperfusion strategies are promising fields of further exploration.

[Reperfusion therapy for patients with an acute myocardial infarct with ST-segment elevation: fibrinolysis versus transport to a cardiac center for primary angioplasty]. / Reperfusietherapie bij patiënten met een acuut myocardinfarct met ST-segmentelevatie: fibrinolyse versus transport naar een hartcentrum voor primaire angioplastiek.

Although fibrinolytic therapy for acute myocardial infarction is widely used and can be administered prior to hospitalisation, it is only successful in restoring full early coronary patency in about 60% of patients and has a 0.5% to 1% risk of severe side effects. Primary percutaneous coronary angioplasty carried out as an alternative to fibrinolysis avoids the risk of fibrinolytic therapy and restores patency in nearly 90% of cases. Data from randomised trials of primary angioplasty versus fibrinolytic therapy in acute myocardial infarction reveal that angioplasty results in a significant reduction in mortality. Furthermore, primary angioplasty can be improved by means of a new pre-angioplasty drug therapy (so-called facilitated primary angioplasty). Transport to a cardiac centre for primary angioplasty (of which there are 14 in the Netherlands) is feasible and safe. Although the time to treatment is delayed by a further 90 minutes, it tends to save lives and prevent strokes and it also significantly reduces the incidence of reinfarction. Interestingly, the time gained to treatment with prehospital fibrinolytic therapy compared to in-hospital therapy gave an outcome similar to that found upon comparing transport and primary angioplasty. Rescue procedures (angioplasty) within 24 hours are necessary in about 30% of patients who are initially treated with lytic therapy. These results support prehospital triage for fibrinolysis or transport to a cardiac centre, where early angioplasty can be performed if clinically indicated. A trial to determine the policy of choice is at present being conducted in the Netherlands.

Successful out-of-hospital cardiopulmonary resuscitation: what is the optimal in-hospital treatment strategy?

UNLABELLED: The aim of the study was to evaluate prognostic factors in patients after successful out-of-hospital resuscitation (sOHR) within 30 min after admission. A prognostic scoring scale in patients surviving OHR was analysed. We also studied the effect of these predictive factors and the in-hospital treatment (percutaneous transluminal coronary angioplasty (PTCA) vs. thrombolysis) on mortality. We performed a retrospective analysis of the emergency medical system forms and medical files of 72 consecutive patients aged > or =18 years with sOHR. Of these 72 patients 37 (51%) met the electrocardiographic and enzymatic criteria for acute myocardial infarction (AMI). Ten of the 37 AMI patients (27%) underwent acute PTCA as primary treatment and seven patients (19%) received thrombolytic therapy for AMI despite prolonged (mean 24+/-13 min) cardiopulmonary resuscitation (CPR). The remaining 20 patients had no specific infarct treatment. Despite successful PTCA, in eight out of ten patients, their mortality in hospital was 60% (6/10). Mortality in the thrombolysis group was 57% (4/7). For the remaining 20 MI-patients the mortality was 65% (13/20). Univariate and multivariate analyses were performed to design a weighted prognostic scoring system. The Glasgow coma scale (GCS) was the strongest independent predictor (r=0.76, P< or =0.001) for in-hospital death. CONCLUSIONS: in-hospital mortality after successful OHR seems to largely depend on neurological status at admission and much less on the specific treatment of myocardial infarction. The prognostic scoring system accurately predicted the in-hospital mortality and can be used for early treatment stratification; however, it should be proven in a prospective study.

Beyond lipids - the role of the endothelium in coronary artery disease.

The beneficial effects of statin therapy in patients with coronary heart disease (CHD) outweigh those expected from simply lowering low-density lipoprotein (LDL) cholesterol, and occur too early in treatment to be due to this mechanism alone. Endothelial dysfunction is present in patients with atherosclerosis, even in the early stages before plaque formation, making it a useful marker for early cardiovascular disease. Statins reduce endothelial dysfunction, which improves myocardial perfusion and angina pectoris. In recent studies with statin therapy, the improvement in endothelial function has been attributed, in part, to an increased production of nitric oxide (NO), a key vasodilator, from the endothelium. These studies have shown that pravastatin and simvastatin improve endothelial function in the short term, with variable effects on vasodilation, which may be due to differences in their effects on NO production. Whether these differences between the statins may result in long-term differences in net clinical benefit has to be awaited.

Comparison of coronary flow velocity and regional myocardial perfusion for functional evaluation of coronary artery disease in the setting of angioplasty.

Two essentially different methods for physiological evaluation of coronary artery disease were compared in the setting of angioplasty and related to quantitative coronary angiography. Forty-five patients, referred for percutaneous transluminal coronary angioplasty (PTCA), were examined by digital subtraction angiography (DSA) and by coronary flow velocity measurements distal to the target stenosis. Before PTCA, hyperemic mean transit time (HMTT) was correlated with % area stenosis r = 0.56*, coronary flow velocity reserve (CFVR) r = 0.58* and with CFVRN (CFVR normalized to a mean blood pressure of 100 mmHg) r = 0.68*. The correlation between CFVR and % area stenosis was r = 0.72* (*P < 0.001). After PTCA, all correlations between these measurements disappeared. HMTT and CFVR remained abnormal in 18% and 32 % of the patients, respectively. Pre-PTCA, distal coronary flow velocity measurements were reasonably well related to the assessment of regional myocardial perfusion. Flow velocity parameters, however, were better related to angiographic stenosis parameters. After PTCA, HMTT showed a more consistent improvement compared to CFVR. Flow velocity measurements appear to be more useful for the evaluation of local coronary stenoses, whereas the assessment of regional myocardial perfusion by DSA may be used for a more general evaluation of vessel territories.

Aggressive lipid lowering treatment in coronary atherosclerosis.

Reduction of cholesterol by potent drugs in clinically symptomatic or asymptomatic patients with elevated cholesterol levels will substantially decrease the risk of coronary events. In selected cases more aggressive treatment of hyperlipidemia is necessary, such as in patients, homozygous for familial hypercholesterolemia, or subjects with severe coronary artery disease who are refractory to diet and drugs. LDL-apheresis, by which atherogenic lipoprotein particles are removed from the blood extracorporeally, is a therapeutic option in these cases. In this report a study is summarized, in which the effect of intervention with LDL-apheresis plus simvastatin was compared with conventional drug treatment alone in a group of patients with severe coronary artery disease with respect to changes in coronary atherosclerotic lesions and their functional impact.

Functional evaluation of lipid-lowering therapy by pravastatin in the Regression Growth Evaluation Statin Study (REGRESS)

BACKGROUND: Lipid-lowering therapy during 2 years in the Regression Growth Evaluation Statin Study (REGRESS) was associated with less progression of coronary atherosclerosis in the pravastatin group compared with the placebo group. The effect of lipid-lowering therapy on the functional state of the coronary circulation is less well known. The purpose of this study was to evaluate this effect. METHODS AND RESULTS: In a substudy of REGRESS, 69 patients were randomized to pravastatin or placebo. Thirty-seven of these patients were allocated to the medical management stratum. Quantitative coronary angiography, regional myocardial perfusion, exercise testing, and classification of angina pectoris were assessed at baseline and after 2 years of therapy. Regional myocardial perfusion was assessed by digital subtraction angiography after intracoronary papaverine with video-densitometric calculation of the hyperemic mean transit time (HMTT) of contrast. In the medical management stratum, regional myocardial perfusion was assessed in 31 regions in the pravastatin group and 25 regions in the placebo group. The change in HMTT in the pravastatin group was -0.18 seconds (-5%) and in the placebo group +0.52 seconds (+18%), a difference of 0.70 seconds (P=.004). The mean difference in change in classification of angina pectoris (scale, 1 to 4) between pravastatin and placebo was 0.7 (P=.03) in favor of the pravastatin-treated patients. The change in HMTT was correlated with the change in exercise time (r=-.65, P=.002). CONCLUSIONS: In patients with symptomatic coronary artery disease, treatment with the HMG-coenzyme A reductase inhibitor pravastatin during 2 years resulted in a preserved regional myocardial perfusion, whereas patients on placebo deteriorated. The classification of angina pectoris improved only in patients receiving pravastatin. In lipid-lowering therapy, the evaluation of myocardial perfusion by assessment of the HMTT reveals a combined measure of functional and structural changes in the coronary circulation.

Low density lipoprotein apheresis improves regional myocardial perfusion in patients with hypercholesterolemia and extensive coronary artery disease. LDL-Apheresis Atherosclerosis Regression Study (LAARS).

OBJECTIVES: In a randomized study we evaluated the effect of biweekly low density lipoprotein (LDL) apheresis plus simvastatin versus medication alone on regional myocardial perfusion. BACKGROUND: In patients with severe hypercholesterolemia, diet and lipid-lowering drugs are often insufficient to achieve optimal LDL cholesterol values. Low density lipoprotein apheresis is a very effective lipid-lowering therapy. Assessment of regional myocardial perfusion enables evaluation of the functional state of the coronary circulation. METHODS: We studied 42 patients with severe hypercholesterolemia and extensive coronary artery disease who were randomized to diet and simvastatin with or without biweekly LDL apheresis. Regional myocardial perfusion was assessed by digital subtraction angiography with videodensitometric calculation of hyperemic mean transit time (HMTT) of contrast medium at baseline and after 2 years of therapy. RESULTS: Low density lipoprotein cholesterol decreased by 63% (to 3.0 mmol/liter) in the LDL apheresis group and by 47% (to 4.1 mmol/liter) in the medication group. Paired HMTT measurements were assessed in 43 regions in the LDL apheresis group and 35 regions in the medication group. In the LDL apheresis group, regional HMTT decreased over 2 years from 3.35 +/- 1.18 (mean +/- SD) to 2.87 +/- 0.82 s (-14%, p = 0.001), whereas no change in the medication group was observed: 2.95 +/- 1.06 to 2.96 +/- 0.90 s (p = NS). In the patient-based comparison, the mean change in HMTT was -0.45 s (-14%, p = 0.01) in the LDL apheresis group and -0.05 s (-2%, p = NS) in the medication group, respectively. Only exercise-induced ischemia improved in the LDL apheresis group. CONCLUSIONS: Biweekly LDL apheresis plus simvastatin decreased time-averaged LDL cholesterol levels by an additional 31% (1.1 mmol/liter) compared with medication alone. After 2 years of therapy, regional myocardial perfusion improved in the LDL apheresis group and remained unchanged in the medication group. Thus, aggressive reduction of LDL cholesterol has a favorable effect on regional myocardial perfusion and alleviates ischemia.