Addition of routinely measured blood biomarkers significantly improves GRACE risk stratification in patients with myocardial infarction.

AIM: To investigate whether blood biomarkers measured routinely at hospital admission in myocardial infarction (MI) patients can improve the admission GRACE score for the composite endpoint of all-cause mortality and non-fatal MI at 6 months. METHODS: 2055 patients treated for MI in the Northwest clinics, the Netherlands, between 2013 and 2016 were examined. As part of the prevailing MI treatment protocol, 19 biomarkers were measured and the GRACE score was ascertained. Information on the composite endpoint was derived from municipal registries and electronic medical records. We applied elastic net logistic regression (LR) analysis to select biomarkers that had statistically significant additive prognostic value on top of the GRACE score. We then studied the prognostic performance of the LR model containing the GRACE score and the selected biomarkers. RESULTS: At six months follow-up 143 (6.96%) reached the composite endpoint. Nine variables were included in the final LR model: GRACE score, urea, sodium, potassium, alkaline phosphatase, LDL cholesterol, glucose, hemoglobin and C-reactive protein. This extended GRACE score model showed improved discrimination (C-statistic 0.76 vs 0.70, p = <0.001) and classification (continuous net reclassification index 0.49, p < 0.001) compared with the GRACE score only. CONCLUSION: The ability of the GRACE score for detecting MI patients at high risk for mortality or MI within 6 months, was significantly improved by adding several biomarkers measured routinely at admission.

[Thrombosis of a coronary stent after discontinuing treatment with clopidogrel]. / Trombose van een coronaire stent na het staken van behandeling met clopidogrel.

A drug-eluting stent was implanted in four patients, a man aged 67 and a woman aged 42 with acute myocardial infarction, a woman aged 41 with unstable angina pectoris and a man aged 41 with stable angina pectoris. All suffered stent thrombosis after discontinuation (in three cases prematurely) of clopidogrel therapy. Reasons for discontinuation included allergic reaction, a dental procedure and refusal of reimbursement by the insurer. In order to restore stent patency they were treated by percutaneous coronary intervention and all patients suffered irreversible myocardial damage. Combination therapy using acetylsalicylic acid and clopidogrel during and after angioplasty for the prevention of long- and short-term complications is necessary. Stent thrombosis after drug-eluting stent implantation usually occurs within 1-4 weeks following discontinuation ofantiplatelet medication. These cases stress the importance of antiplatelet therapy after stent implantation. Physicians, dentists and patients must be aware of the risk of the early discontinuation ofantiplatelet therapy.

Efficacy of spinal cord stimulation as adjuvant therapy for intractable angina pectoris: a prospective, randomized clinical study. Working Group on Neurocardiology.

OBJECTIVES: In a prospective, randomized study with an 8-week follow-up period, we evaluated the efficacy of spinal cord stimulation on exercise capacity and quality of life in patients with intractable angina. BACKGROUND: Despite important achievements in therapy for ischemic heart disease, there remain patients with intractable symptoms of angina. In uncontrolled observations, several investigators have reported beneficial effects of spinal cord stimulation as an additional therapy for patients with angina pectoris. METHODS: Seventeen patients were randomly assigned to the treatment (implantation within 2 weeks, eight patients) or control (implantation after 8 weeks, nine patients) group. Assessment of exercise capacity was performed by treadmill exercise testing. Quality of life was evaluated by daily and social activity scores and recording sublingual glyceryl trinitrate intake and angina pectoris attacks in a diary. After the 8-week study period, the control group also received the spinal cord stimulation device, and all patients were followed up for 12 months. RESULTS: The treatment but not the control group demonstrated a significant increase in exercise duration (p < 0.02), rate-pressure product (p < 0.03) and time to angina (p < 0.04), with a decrease in ST segment depression (p < 0.05). This was associated with an increase in daily life (p < 0.008) and social activity (p < 0.005) scores and a reduction in glyceryl trinitrate intake (p < 0.004) and episodes of angina pectoris (p < 0.003). During the 1-year follow-up, improvement in all quality of life variables was linear for the entire group compared with baseline. The time to angina, exercise duration and ST segment depression showed a second-order trend. CONCLUSIONS: Spinal cord stimulation significantly improves exercise capacity and quality of life. On the basis of an increase in exercise capacity and rate-pressure product, the mechanism by which spinal cord stimulation acts may be related to improved oxygen supply to the heart combined with an analgesic effect.

Coronary blood flow dynamics during transcutaneous electrical nerve stimulation for stable angina pectoris associated with severe narrowing of one major coronary artery.

To study the effect of transcutaneous electrical nerve stimulation (TENS) on coronary vasomotion, patients with New York Heart Association class III angina pectoris and significant single-vessel left coronary artery disease and who were also scheduled for elective percutaneous transluminal coronary angioplasty, were allocated to a study group (precordial actual TENS, n = 10) and a control group (precordial simulated TENS, n = 5, and TENS on the back, n = 3). Coronary volumetric flow was assessed in the stenotic and nonstenotic coronary artery before and after neurostimulation. The diameter (in millimeters) of the stenotic coronary artery was reduced in the study group after actual TENS (from 2.73 +/- 0.55 by 0.12 +/- 0.11; p = 0.008). In the nonstenotic coronary artery, the diameter increased in the study group (from 2.64 +/- 0.43 by 0.24 +/- 0.15; p = 0.01). In both the stenotic and nonstenotic coronary arteries, no effect was shown on the average peak velocity (centimeters per second) in the study group. The coronary volumetric flow (milliliters per minute) was reduced in the stenotic artery of the study group (from 62 +/- 18 by 8 +/- 7; p = 0.007). In the nonstenotic coronary artery, volumetric flow increased in the study group (from 57 +/- 18 by 11 +/- 10; p = 0.007). In the control group, simulated TENS and TENS on the back had no effect on the diameter of the artery, average peak velocity, or volumetric flow. In addition, in all patients, TENS had no effect on the total volumetric flow of the left coronary artery and hemodynamic variables during the study period. This observation suggests that TENS modulates regional coronary vasomotion in patients with coronary artery disease.

Effect of spinal cord stimulation on myocardial blood flow assessed by positron emission tomography in patients with refractory angina pectoris.

Spinal cord stimulation in angina pectoris increases exercise capacity and reduces both anginal attacks and ischemic electrocardiographic signs. This suggests an anti-ischemic action, perhaps through changes in myocardial blood flow. In 9 patients, regional myocardial blood flow was studied with positron emission tomography before and after 6 weeks of spinal cord stimulation, both at rest and during a dipyridamole stress test. Frequency of anginal attacks and consumption of short-acting nitrates were assessed by patient diaries. Exercise duration and time to angina were measured with treadmill exercise tests. After 6 weeks of stimulation, both frequency of daily anginal attacks and nitrogen consumption decreased (3.7 +/- 1.7 vs 1.4 +/- 1.0 [p <0.01] and 2.8 +/- 2.2 vs 1.1 +/- 1.2 tablets [p = 0.01], respectively); exercise duration and time to angina increased (358 +/- 165 vs 493 +/- 225 seconds [p <0.01] and 215 +/- 115 vs 349 +/- 213 seconds [p = 0.02], respectively); and ST-segment depression during dipyridamole stress testing was reduced (0.17 [0 to 0.5] mV vs 0.09 [0 to 0.2] mV, p = 0.04) (all data mean +/- SD). Total resting blood flow remained unchanged (115 +/- 29 vs 127 +/- 31 ml/min/100 g, p = 0.31), but flow reserve decreased (146 +/- 43% vs 122 +/- 39%, p = 0.04). The coefficient of variation of flow, representing flow heterogeneity, decreased after treatment, both at rest (20.1 +/- 3.8% vs 17.4 +/- 2.6%, p = 0.04) and after dipyridamole stress (26.2 +/- 4.4% vs 22.9 +/- 5.5%, p = 0.02). Thus, spinal cord stimulation is clinically effective due to homogenization of myocardial blood flow. Since flow reserve decreases despite clinical improvement, the dipyridamole effect may be blunted by spinal cord stimulation.

Transneuronal viral labelling of rat heart left ventricle controlling pathways.

Retrograde transneuronal viral labelling and immunocytochemical methods were used for revealing neuronal networks controlling the left ventricle myocardium of the rat heart. After injections of 1 microliter pseudorabies virus solution (3 x 10(6) PFU ml-1) into the left ventricle, infected orthosympathetic preganglionic cells were found in the intermediolateral cell groups of the first 6 thoracic spinal segments. Preganglionic parasympathetic neurones were seen both in the nucleus ambiguus/retro-ambiguus area and the dorsal motor vagus nucleus. Large numbers of infected projecting interneurones were found in the rostral, caudal and medial parts of the ventral medulla oblongata, the Kölliker-Fuse nucleus and catecholaminergic cell group A5 and in the paraventricular hypothalamic nucleus.

Electrical neuromodulation improves myocardial perfusion and ameliorates refractory angina pectoris in patients with syndrome X: fad or future?

At present, there is no reliable antianginal drug therapy for patients with cardiac syndrome X. Therefore, the effect of electrical neuromodulation on refractory angina pectoris and myocardial perfusion in cardiac syndrome X was assessed. Eight patients (aged 55+/-7 years) with heterogeneous myocardial perfusion and no esophageal abnormalities were included. The subjects were nonresponders to antianginal drug therapy. Angina pectoris attacks and myocardial perfusion dynamics were evaluated by positron emission tomography at baseline and following 4 weeks of (transcutaneous electrical nerve stimulation) TENS. Following TENS there was a reduction of angina pectoris episodes (baseline 20+/-3, TENS 3+/-1; p=0.012), and short acting nitroglycerin intake per week (baseline 10+/-3, TENS 2+/-1; p=0.008). The rate pressure product (mmHg min(-1)) during the cold pressor test (CPT) was reduced during TENS (baseline 12800+/-1200, TENS 11500+/-900; p=0.02). Following TENS, the perfusion reserve ratio between rest and dipyridamole flow increased (baseline 1.59+/-0.15, TENS 1.90+/-0.11 ml min(-1)x 100g; p=0.05). The coronary vascular resistance had a trend towards a reduction (baseline 0.96+/-0.04, TENS 0.85+/-0.06 mmHg min(-1)x 100 g/ml; p=0.06) during CPT. This observation may suggest that neurostimulation improves angina pectoris with a concomitant improvement of myocardial perfusion in cardiac syndrome X.

Electrical neuromodulation for disabling angina pectoris related to isolated stenoses of small epicardial coronary arteries.

Patients with symptomatic small vessel coronary artery disease may be inadequate candidates for revascularization procedures. They may suffer from refractory angina, which does not respond to maximal anti-anginal drug therapy. In addition to patients with end stage coronary artery disease and syndrome X, this newly defined group of subjects with an isolated stenosis of a small coronary artery may benefit from electrical neurostimulation. We describe two patients with intractable angina caused by a significant narrowing of a diagonal branch. This treatment modality should be considered as an alternative method for unsatisfactory revascularization procedures.

Effect of spinal cord stimulation on heart rate variability and myocardial ischemia in patients with chronic intractable angina pectoris--a prospective ambulatory electrocardiographic study.

BACKGROUND AND HYPOTHESIS: Spinal cord stimulation is an effective treatment for chronic refractory angina pectoris. Its efficacy is related to an anti-ischemic action, possibly as a result of modulation of the autonomic nervous system. Therefore, the influence of spinal cord stimulation on the autonomic nervous system and myocardial ischemia was prospectively studied in 19 consecutive patients with intractable angina pectoris. METHODS: Patients were included when demonstrating > 0.1 mV STsegment depression on the exercise electrocardiogram (ECG) during two separate treadmill tests. After enrollment, heart rate variability together with ischemic indices were studied with 48 h ambulatory ECG monitoring. Assessments were made at baseline and after 6 weeks of spinal cord stimulation therapy. RESULTS: After 6 weeks, no significant changes in heart rate variability were detected. However, ischemic indices on the ambulatory ECG, as well as anginal attacks and consumption of sublingual nitrate tablets, were significantly decreased. CONCLUSION: Autonomic modulation assessable with heart rate variability analysis may not be the explanatory mechanism of action for the decrease of anginal attacks and ischemia, exerted by spinal cord stimulation used as an adjuvant therapy in patients with chronic intractable angina pectoris.

Angina pectoris refractory for conventional therapy--is neurostimulation a possible alternative treatment?

The treatment of angina pectoris as a symptom of coronary artery disease usually is focused on restoring the balance between oxygen demand and supply of the myocardium by administration of drugs interfering in heart rate, cardiac pre- and afterload, and coronary vascular tone. For nonresponders to drug therapy or for those with jeopardized myocardium, revascularization procedures such as coronary bypass surgery and percutaneous transluminal coronary angioplasty are at hand. However, the atherosclerotic process is not stopped by these therapies and, at longer terms, angina may recur. It is not always possible to revascularize all the patients who do not positively react to medical treatment. Those with angina, not responding to adequate medication and who are not suitable anymore for revascularization, are considered to suffer from refractory angina pectoris. This group of patients has a poor quality of life, for their exercise tolerance is severely afflicted. For these patients, neurostimulation has been described repeatedly as an effective and safe therapy. The mechanism of action of neurostimulation is not completely known, but recent studies suggest an anti-ischemic effect, exerted through changes in myocardial blood flow. As soon as its safety is sufficiently established, it may become a useful alternative in the treatment of refractory angina pectoris.

Nursing role to improve care to infarct patients and patients undergoing heart surgery: 10 years' experience.

BACKGROUND: The nurse practitioner may be the ideal healthcare worker to create a new environment and may facilitate in the process of expediting discharge and improving patient safety. They can play an intermediary role between the consultants, nurses and patients, thereby combining the aspects of care (nursing) and cure (physicians). METHOD: We describe the contribution and role of the nurse practitioner in a teaching hospital and provide an overview of the changes in care and cure that were facilitated by two nurse practitioners in the treatment of cardiac surgery patients or non-complicated acute coronary syndrome patients. RESULTS: The nurse-led clinic for postoperative patients has registered 1967 patients in the past 10 years. These patients were transferred at a mean of 5.5 days after their bypass operation. All patients had an uneventful clinical course in our hospital and were discharged alive. The period between discharge and outpatient clinic visit could be set at 4 weeks. The post-acute coronary syndrome (ACS) group included 1236 patients. Mortality in this patient cohort was 4% while 0.4% of these patients experienced a re-myocardial infarction. Additional surgery was needed in only 2% of these stable post-infarction patients. The mean length of stay was 5.9 ± 14.5 days. CONCLUSION: This observational study confirms that a nurse-led postoperative care unit and post-ACS care unit is feasible and effective for the treatment of patients returning from cardiac surgery or transferred after uncomplicated ACS to a general cardiology ward.

Percutaneous coronary intervention without on site surgical back-up; two-years registry of a large Dutch community hospital.

AIMS: To assess safety and efficacy of off-site percutaneous coronary intervention (PCI) in The Dutch invasive cardiovascular system. METHODS AND RESULTS: Descriptive single centre registry of elective and emergency PCI. Setting is a Dutch community hospital, 40 km north of Amsterdam, with an adherent population of 400,000 people. A Clinical follow up of Major Adverse Cardiac and Cerebral Events (MACCE) at 30 days post PCI is performed. The total number of participants eligible for PCI was 781 of whom 545 were men and 236 women. During a two-year period 781 PCI's were performed of which 298 were emergency and 483 elective. Acute complications occurred in 2.1% of participants. MACCE-free was 86.9% in the group with AMI and 95.8% in the elective group. CONCLUSIONS: Off-site PCI is feasible and safe in The Netherlands on the condition that specific key factors for success are taken into consideration.

Neuroanatomy of cardiac activity-regulating circuitry: a transneuronal retrograde viral labelling study in the rat.

The anatomy of cardiac activity-regulating circuitry was studied with retrograde transneuronal viral labelling after pseudorabies virus injections into different parts of the rat heart. Transection of the spinal cord at Th1 was used to reveal selectively the parasympathetic neuronal networks. Virus-labelled sympathetic preganglionic cells were found in the Th1-Th7 thoracic intermediolateral cell groups, with some additional infections at Th8-Th11 after inoculations of the ventricular myocardium. After ventricular injections the thoracic spinal labelling pattern was bilateral and after right atrial infection it was contralateral. Approximately 20% of the parasympathetic preganglionic cells were located in the dorsal motor vagus nucleus; the rest occupied positions in the peri-ambiguus area ventrolateral to the nucleus ambiguus. Here and in the ventrolateral reticular formation myocardiotopy was found. Supraspinal transneuronal infections were bilateral, showed no apparent side dominance and were found in the nucleus of the solitary tract, the area postrema, the raphe nuclei, the A5 group, the parabrachial region, the periaqueductal grey, the hypothalamus, the amygdala and the cortex, in particular the anterior cingulate, the frontal, prelimbic, infralimbic and insular cortices. Spinal transections at Th1 reduced the number of labelled cells, gave a right side labelling dominance and affected the infection patterns in the ventrolateral reticular area, the raphe nuclei, the periaqueductal grey matter, the perifornical and retrochiasmatic area and the rostral parts of the insular cortex. The latter structures are linked selectively to the sympathetic innervation of the heart. The anatomical and functional aspects of these findings are discussed in relation to the autonomic control of heart activity.

Spinal Cord Stimulation and the Induction of c-fos and Heat Shock Protein 72 in the Central Nervous System of Rats.

For more than a decade, spinal cord stimulation (SCS) has been used as an adjuvant treatment for patients who are unresponsive to conventional therapies for angina pectoris. Many studies showed that SCS has both electro-analgesic and anti-ischemic effects. Nonetheless, the biological substrates by which SCS acts have not yet been unraveled, although recently areas in the brain have been described that show changes in blood flow, following SCS, and during provocation of angina. In search of a putative mechanism of action of SCS, we hypothesized that SCS affects processing of nociceptive information within the central nervous system (CNS). Moreover, it may alter the limbic system activity that maintains the balance between sympathetic and parasympathetic activity in the heart. Hence, we have developed a rat model to investigate its suitability for studying the induction of neural activity during SCS. To characterize neural activity, we used the expression of both the immediate early gene c-fos and the heat shock protein 72 (HSP72). c-Fos was used to identify structures in the CNS affected by SCS, and HSP72 was applied in order to ascertain whether SCS might operate as a stressor. In 20 halothane-anesthetized male Wistar rats, two electrodes were placed epidurally, one at the C7 level and the other at the T2 level. Two days after surgery, the rats were either stimulated "treated" animals, n = 10) or used as controls ("unstimulated" = "sham," n = 10) in random order. Furthermore, we studied the effect of SCS on behavior in five treated and five control rats. Three hours after stimulation, the rats were euthanized and the brain and spinal cord were removed. The treated group showed regional increased c-fos expression in regions of the limbic system (periaqueductal gray, paraventricular hypothalamic nucleus, paraventricular thalamic nucleus, central amygdala, agranular and dysgranular insular cortex, (peri)ambiguus, nucleus tractus solitarius, and spinal cord) that are involved in the processing of pain and cardiovascular regulation, among other things. Moreover, in both treated rats and controls, HSP72-expression was found in the endothelium of the enthorhinal cortex, the amygdala, and the ventral hypothalamus, but not in the neurons. Finally, treated animals were significantly more alert and active than controls. In conclusion, the rat model we developed appears to be suitable for studying potential mechanisms through which SCS may act. In addition, SCS affects c-fos expression in specific parts of the brain known to be involved in regulation of pain and emotions. HSP72-expression is limited to the endothelium of certain parts of the CNS and thereby excludes physical stress effects as a potential mechanism of SCS.

Spinal cord stimulation in chronic intractable angina pectoris: a randomized, controlled efficacy study.

BACKGROUND: Spinal cord stimulation is known to be a successful treatment for chronic intractable angina pectoris. Its effect may be anti-ischemic. It is uncertain if the clinical effect is partly caused by a placebo effect of surgery for implantation of a stimulator. In this study, clinical efficacy is investigated, together with a possible placebo effect. METHODS AND RESULTS: Efficacy of spinal cord stimulation as a treatment for chronic intractable angina pectoris was studied for 6 weeks in 13 treated patients and 12 control patients with chronic angina. Assessments were exercise capacity and ischemia, daily frequency of anginal attacks and nitrate tablet consumption, and quality of life (perceived quality of life and pain). Compared with control, exercise duration (P =.03) and time to angina (P =.01) increased; anginal attacks and sublingual nitrate consumption (P =.01) and ischemic episodes on 48-hour electrocardiogram (P =.04) decreased. ST-segment depression on the exercise electrocardiogram decreased at comparable workload (P =.01). Anginal attacks and consumption of sublingual nitrates decreased (P =.01), perceived quality of life increased (P =.03), and pain decreased (P =.01). CONCLUSIONS: Spinal cord stimulation is effective in chronic intractable angina pectoris, and its effect is exerted through anti-ischemic action. Efficacy is unlikely to be explained as a placebo effect from surgery.

Relative changes in regional cerebral blood flow during spinal cord stimulation in patients with refractory angina pectoris.

Spinal cord stimulation applied at thoracic level 1 (T1) has a neurally mediated anti-anginal effect based on anti-ischaemic action in the myocardium. Positron emission tomography was used to study which higher brain centres are influenced by spinal cord stimulation. Nine patients with a spinal cord stimulator for angina pectoris were studied using H(2)(15)O as a flow tracer. Relative changes in regional cerebral blood flow related to stimulation compared with non-stimulation were assessed and analysed using the method of statistical parametric mapping. Increased regional cerebral blood flow was observed in the left ventrolateral periaqueductal grey, the medial prefrontal cortex [Brodmann area (BA) 9/10], the dorsomedial thalamus bilaterally, the left medial temporal gyrus (BA 21), the left pulvinar of the thalamus, bilaterally in the posterior caudate nucleus, and the posterior cingulate cortex (BA 30). Relative decreases in rCBF were noticed bilaterally in the insular cortex (BA 20/21 and BA 38), the right inferior temporal gyrus (BA 19/37), the right inferior frontal gyrus (BA 45), the left inferior parietal lobulus (BA 40), the medial temporal gyrus (BA 39) and the right anterior cingulate cortex (BA 24). It is concluded that spinal cord stimulation used as an additional treatment for angina applied at T1 modulates regional cerebral blood flow in brain areas known to be associated with nociception and in areas associated with cardiovascular control.

Effects of spinal cord stimulation on myocardial ischaemia during daily life in patients with severe coronary artery disease. A prospective ambulatory electrocardiographic study.

BACKGROUND: Spinal cord stimulation (SCS) may be a useful additional therapy for pain in patients with therapeutically refractory angina pectoris. But doubts remain about whether it also relieves ischaemia. METHODS: Indices of ischaemia were studied with and without SCS in 10 patients with otherwise intractable angina and evidence of myocardial ischaemia on 48 h ambulatory electrocardiographic (ECG) recording. Primary end points assessed by 48 h ECG recordings were total ischaemic burden, number of ischaemic episodes, and duration of ischaemic episodes. In addition, symptoms were assessed by a diary of glyceryl trinitrate intake and angina attacks. RESULTS: During SCS the total ischaemic burden of the entire group was significantly reduced from a median of 27.9 (1.9-278.2) before SCS to 0 (0-70.2) mm x min with SCS (p < 0.03). In six out of the 10 patients there was no myocardial ischaemia during 48 h ambulatory ECG monitoring with SCS. The number of ischaemic episodes was reduced from a median of 3 (1-15) before SCS to 0 (0-9) with SCS (p < 0.04). The duration of ischaemic episodes decreased from a median of 20.6 (1.7-155.4) min before SCS to 0 (0-48.3) min with SCS (p < 0.03). This was accompanied by a significant improvement in symptoms with a reduction in daily glyceryl trinitrate intake from a median of 3.0 (0-10) before SCS to 0.3 (0-10) tablets per 48 h (p < 0.02) and a decrease in the frequency of anginal attacks from a median of 5.5 (2-14) before SCS to 1.0 (0-10) per 48 h with SCS (p < 0.03). CONCLUSIONS: SCS not only reduced symptoms but also myocardial ischaemia. Therefore, SCS appears to be both a safe and an effective therapy for patients with refractory angina.

Randomised, double-blind trial of intravenous diltiazem versus glyceryl trinitrate for unstable angina pectoris.

The effect of dihydropyridines in patients with unstable angina is discouraging. To find out the effect of the non-dihydropyridine-like calcium-channel blocker diltiazem, a randomised, double-blind trial was conducted comparing diltiazem with glyceryl trinitrate, both given intravenously, in 129 patients with unstable angina. The endpoints were refractory angina or myocardial infarction, individually and as a composite endpoint. Refractory angina alone or together with myocardial infarction occurred significantly less commonly in the diltiazem group. While patients were on the trial drugs the numbers with refractory angina were 6 (10%) in the diltiazem group versus 17 (28%) in the glyceryl trinitrate group (relative risk 0.36, p = 0.02), and the numbers with refractory angina and myocardial infarction were 9 (15%) versus 23 (38%) (relative risk 0.40, p = 0.007). Over 48 h the number were: refractory angina 8 (13%) versus 18 (30%), relative risk 0.45, p = 0.03, and refractory angina and myocardial infarction 12 (20.0%) versus 25 (41%), relative risk 0.49, p = 0.02. Patients in the diltiazem group had better (p < 0.05) event-free survival while taking the drugs. Heart-rate pressure product was reduced significantly only by diltiazem (p < 0.05). The incidence of bradyarrhythmias did not differ significantly. Atrioventricular conduction disturbances occurred in 5 (8%) patients in the diltiazem group but were not seen in the glyceryl trinitrate group (p = 0.03). These disturbances could be reversed by decreasing the dose of the drug or withdrawing it. No temporary pacemakers were required. Headache requiring an analgesic or dose adjustment occurred significantly less in the diltiazem group: 3 (5%) versus 15 (25%), relative risk 0.20 (p < 0.004). These results indicate that intravenous diltiazem, compared with intravenous glyceryl trinitrate, significantly reduces ischaemic events and can be used safely in patients with unstable angina.

Clinical follow-up after cessation of chronic electrical neuromodulation in patients with severe coronary artery disease: a prospective randomized controlled study on putative involvement of sympathetic activity.

The present study assessed the reoccurrence of myocardial ischemia after withholding electrical neurostimulation. After randomization, in the study or withdrawal group, spinal cord stimulation (SCS) was set active during the first 4 weeks, followed by 4 weeks of withholding stimulation. In the control group, SCS was switched off during 4 weeks before the end of the study. The control group had no crossover period. Measurements were done at baseline, then after 4 and 8 weeks. The first periods at 4 weeks of each sequence of both groups were compared. In addition, a comparison of clinical variables was performed between the study group 4 weeks after withholding stimulation and the control group 4 weeks following randomization. A total number of 24 patients with refractory angina and an implanted spinal cord stimulator were included in the study (n = 12) and control group. Angina pectoris complaints, nitroglycerin intake, ischemia, and heart rate variability using 48-hour ambulatory electrocardiographic monitoring were assessed. In addition, neurohormonal status and symptom-limited aerobic capacity were evaluated. There was no increase of anginal complaints or ischemia after withholding stimulation. Neurohormonal levels and aerobic capacity were not altered. We conclude that there is no adverse clinical rebound phenomenon after withholding neurostimulation in patients with refractory angina pectoris.