Long-term prognostic value of quantitative myocardial perfusion in patients with chest pain and normal coronary arteries.

BACKGROUND: Patients with chest pain and no obstructive coronary artery disease have shown a high incidence of major adverse cardiovascular events (MACE). We evaluated the role of absolute myocardial perfusion quantification in predicting all-cause mortality and MACE during long-term follow-up in this group of patients. METHODS: We studied 79 patients who underwent Nitrogen-13 ammonia PET for quantification of global myocardial blood flow (MBF) and myocardial flow reserve (MFR) due to suspected impaired myocardial perfusion. Patients with coronary artery disease (i.e., > 30% stenosis in one or more coronary arteries) were excluded. We assessed all-cause mortality and MACE. MACE was defined as the composite incidence of death, myocardial infarction (MI), or hospitalization due to heart failure. RESULTS: Median follow-up was 8 (IQR: 3-14) years. Univariate Cox regression showed that only MFR (P = 0.01) was a predictor of all-cause mortality. Univariate Cox regression analysis showed that both MFR and Stress MBF were predictors of the composite endpoint of MACE (P < 0.001 and P = 0.01, respectively). CONCLUSION: Quantitative assessment of myocardial perfusion may predict all-cause mortality and MACE in patients with chest pain and normal coronary arteries in the long-term follow-up.

Patients undergoing elective coronary artery bypass grafting exhibit poor pre-operative intakes of fruit, vegetables, dietary fibre, fish and vitamin D.

CHD may ensue from chronic systemic low-grade inflammation. Diet is a modifiable risk factor for both, and its optimisation may reduce post-operative mortality, atrial fibrillation and cognitive decline. In the present study, we investigated the usual dietary intakes of patients undergoing elective coronary artery bypass grafting (CABG), emphasising on food groups and nutrients with putative roles in the inflammatory/anti-inflammatory balance. From November 2012 to April 2013, we approached ninety-three consecutive patients (80% men) undergoing elective CABG. Of these, fifty-five were finally included (84% men, median age 69 years; range 46-84 years). The median BMI was 27 (range 18-36) kg/m(2). The dietary intake items were fruits (median 181 g/d; range 0-433 g/d), vegetables (median 115 g/d; range 0-303 g/d), dietary fibre (median 22 g/d; range 9-45 g/d), EPA+DHA (median 0.14 g/d; range 0.01-1.06 g/d), vitamin D (median 4.9 µg/d; range 1.9-11.2 µg/d), saturated fat (median 13.1% of energy (E%); range 9-23 E%) and linoleic acid (LA; median 6.3 E%; range 1.9-11.3 E%). The percentages of patients with dietary intakes below recommendations were 62% (fruits; recommendation 200 g/d), 87 % (vegetables; recommendation 150-200 g/d), 73% (dietary fibre; recommendation 30-45 g/d), 91% (EPA+DHA; recommendation 0.45 g/d), 98% (vitamin D; recommendation 10-20 µg/d) and 13% (LA; recommendation 5-10 E%). The percentages of patients with dietary intakes above recommendations were 95% (saturated fat; recommendation < 10 E%) and 7% (LA). The dietary intakes of patients proved comparable with the average nutritional intake of the age- and sex-matched healthy Dutch population. These unbalanced pre-operative diets may put them at risk of unfavourable surgical outcomes, since they promote a pro-inflammatory state. We conclude that there is an urgent need for intervention trials aiming at rapid improvement of their diets to reduce peri-operative risks.

Prevalence and misdiagnosis of chronic heart failure in nursing home residents: the role of B-type natriuretic peptides.

BACKGROUND/OBJECTIVES: Without knowing the exact CHF prevalence, chronic heart failure (CHF) occurs frequently in elderly people both inside and outside nursing homes. For a diagnosis we have to rely on physical examination and additional tests. We therefore run the risk of missing CHF diagnoses or of diagnosing CHF when we should not. Natriuretic peptide assays have emerged as a diagnostic test but their use in nursing home residents is limited. We examined the number of misdiagnoses, the CHF prevalence and the role of natriuretic peptide. METHOD: Residents in one centre without aphasia, cognitive impairments or metastatic cancer were screened for CHF; the natriuretic peptide levels were measured separately. RESULTS: Of the 150 residents, 103 (64%) were included (79+/-11 years). The diagnosis of CHF was established in 24 of these 103 residents with NTproBNP 1871 (IQR 539 to 4262) and BNP 194 (IQR 92 to 460) pg/ml. A striking result was that of the 24 residents found to have CHF after the screening, 15 (66%) had previously been undetected: NT-proBNP 1146 (interquartile range (IQR) 228 to 3341) and BNP 200 (IQR 107 to 433) pg/ml. Moreover, in 13 out of 22 residents (62%) who had previously been thought to have CHF, the diagnosis was rejected: NT-proBNP 388 (IQR 174 to 719) and BPN 90 (IQR 35 to 128) pg/ml). Regarding the diagnostic accuracy of NT-proBNP and BNP, the optimal cut-off level of NT-proBNP was 450 pg/ml with a sensitivity of 0.71 and specificity of 0.67, and for BNP it was 100 pg/ml with a sensitivity of 0.71 and specificity of 0.70. CONCLUSION: Both undetected and incorrect diagnoses of CHF were common. NT-proBNP and BNP were moderately accurate at diagnosing CHF. CHF prevalence was 23%. (Neth Heart J 2008;16:123-8.).

Spinal cord stimulation for ischemic heart disease and peripheral vascular disease.

Ischemic disease (ID) is now an important indication for electrical neuromodulation (NM), particularly in chronic pain conditions. NM is defined as a therapeutic modality that aims to restore functions of the nervous system or modulate neural structures involved in the dysfunction of organ systems. One of the NM methods used is chronic electrical stimulation of the spinal cord (spinal cord stimulation: SCS). SCS in ID, as applied to ischemic heart disease (IHD) and peripheral vascular disease (PVD), started in Europe in the 1970s and 1980s, respectively. Patients with ID are eligible for SCS when they experience disabling pain, resulting from ischaemia. This pain should be considered therapeutically refractory to standard treatment intended to decrease metabolic demand or following revascularization procedures. Several studies have demonstrated the beneficial effect of SCS on IHD and PVD by improving the quality of life of this group of severely disabled patients, without adversely influencing mortality and morbidity. SCS used as additional treatment for IHD reduces angina pectoris (AP) in its frequency and intensity, increases exercise capacity, and does not seem to mask the warning signs of a myocardial infarction. Besides the analgesic effect, different studies have demonstrated an anti-ischemic effect, as expressed by different cardiac indices such as exercise duration, ambulatory ECG recording, coronary flow measurements, and PET scans. SCS can be considered as an alternative to open heart bypass grafting (CABG) for patients at high risk from surgical procedures. Moreover, SCS appears to be more efficacious than transcutaneous electrical nerve stimulation (TENS). The SCS implantation technique is relatively simple: implanting an epidural electrode under local anesthesia (supervised by the anesthesist) with the tip at T1, covering the painful area with paraesthesia by external stimulation (pulse width 210, rate 85 Hz), and connecting this electrode to a subcutaneously implanted pulse generator. In PVD the pain may manifest itself at rest or during walking (claudication), disabling the patient severely. Most of the patients suffer from atherosclerotic critical limb ischemia. All patients should be therapeutically refractory (medication and revascularization) to become eligible for SCS. Ulcers on the extremities should be minimal. In PVD the same implantation technique is used as in IHD except that the tip of the electrode is positioned at T10-11. In PVD the majority of the patients show significant reduction in pain and more than half of the patients show improvement of circulatory indices, as shown by Doppler, thermography, and oximetry studies. Limb salvage studies show variable results depending on the stage of the trophic changes. The underlying mechanisms of action of SCS in PVD require further elucidation.

Effect of right ventricular pacing on ventricular rhythm during atrial fibrillation.

In 13 patients with atrial fibrillation, the effect of right ventricular pacing at various rates on spontaneous RR intervals was studied. Five hundred consecutive RR intervals were recorded and measured before and during varying right ventricular pacing rates. As anticipated, all RR intervals longer than the right ventricular pacing intervals were abolished. However, RR intervals shorter than the right ventricular pacing intervals were also eliminated. It is difficult to explain the elimination of RR intervals shorter than the pacing intervals with the accepted concepts concerning the mechanisms governing the rate and rhythm of the ventricular response to atrial fibrillation. An alternative explanation may be that during atrial fibrillation the atrioventricular node behaves as a nonprotected pacemaker that is electrotonically modulated by the chaotic atrial electrical activity. The result is a random ventricular rhythm. With right ventricular pacing, the automatic focus is depolarized by the retrogradely concealed conducted ventricular impulses, the short RR intervals are not generated as a consequence and the rhythm becomes pacemaker dependent.

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.

Negative inotropic effects of recombinant interleukin 2 in patients without left ventricular dysfunction.

UNLABELLED: Experimental data have shown that rIL2 has negative inotropic properties. This has not been investigated in humans with normal left ventricular function. Seventeen consecutive renal cell carcinoma patients who received rIL2 therapy because of dissemination were analyzed before and after treatment with a low dose of rIL2 subcutaneously. Left ventricular ejection fraction (echocardiography), heart rate variability parameters (24 h electrocardiography), and TNF alpha, IL1 beta and nitric oxide metabolites (NO(x)) were measured. LVEF decreased from 54+/-7 to 50+/-6% (mean+/-S.D.; P=0.012), with a concomitant increase in heart rate from 87+/-13 to 94+/-13 beats/min (P=0.031). All frequency domain HRV parameters decreased: the total power from 18.0+/-7.9 to 14.0+/-5.0 ms (P=0.001), the low frequency from 10.3+/-5.4 to 8. 3+/-3.4 ms (P=0.001), and the high frequency from 6.3+/-2.6 to 4. 5+/-1.1 ms (P=0.001). There was no measurable effect on TNF alpha, IL1 beta concentrations. Plasma levels of nitrate (NO(x)) increased from 22.8+/-14.4 to 41.8+/-26.6 micromol/l (P=0.007). CONCLUSIONS: A low dose of rIL2 has a negative inotropic effect that may be mediated by increased NO concentrations. It also reduces sympathetic activity as reflected in HRV parameters.

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.

Clinical evaluation of pain treatment with electrostimulation: a study on TENS in patients with different pain syndromes.

OBJECTIVE: We evaluated the clinical efficacy and the unwanted side effects of transcutaneous electrical nerve stimulation (TENS) in a consecutive group of patients with intractable pain due to different pain syndromes. METHODS: Two hundred eleven patients with different pain syndromes, coded according to the International Association for the Study of Pain (IASP), were treated with TENS, using a standardized protocol. After a 6-month treatment period, an independent investigator estimated the effect of TENS in retrospect through assessment of patient files, standardized questionnaires, and diaries. In addition, a physical examination to determine the IASP code was performed, and unwanted side effects were evaluated. RESULTS: TENS showed a favorable response in the majority of patients with pain caused by peripheral nerve damage (53%), anginal pain resulting from ischemic heart disease (75%), and pain of the musculoskeletal system due to mechanical degenerative causes (69%). TENS employed in patients with prominent psychological and social distress, and for pain caused by central and autonomic dysfunction, alleviated pain in only 10-25% of the patients. Side effects occurred in 35% during the initial period of the treatment and were usually able to be resolved, especially with thorough supporting instructions during the initial treatment period. CONCLUSIONS: In this study, the beneficial effect of TENS appeared to be related to the etiology of the underlying pain. The effect of TENS was maintained for > 6 months in the majority of patients with an immediate favorable response. Supporting instructions are crucial for long-term success.

Intractable ventricular tachycardia in a patient with giant cell myocarditis, thymoma and myasthenia gravis.

A 48-year-old man presented with a malignant thymoma in combination with myositis, myasthenia gravis, a giant cell myocarditis and recurrent intractable ventricular tachycardias. Despite various therapies (chemical, electrical and surgical), arrhythmias supervened in the presence of a normal coronary arteriogram. Active myocarditis was believed to be the mechanism of the ventricular tachycardias.

Permanent cardiac pacing in children: morbidity and efficacy of follow-up.

The data from 50 permanently paced children [mean standard deviation follow-up 5.3 +/- 3.7 years] were reviewed, with special attention being paid to the cause of complications and the efficacy of follow-up. The 5-year survival (SD) of the patients was 78 +/- 6%; mortality was mainly due to the underlying cardiac disease. The 5-year survival (SD) of the pacing systems was 48 +/- 8%. Surgical interventions were necessary every 4.9 patient years. Of these interventions, 58% were caused by lead-related problems. Epicardial leads showed significantly more exit blocks and high thresholds than endocardial leads. Endocardial leads, therefore, should be used at a younger age than is now the current practice, from 5 years of age onwards, for example. If epicardial leads are used, the pacemaker must have a high output facility. Since exit block occurred only within the first 3 months after implantation, we suggest frequent transtelephonic monitoring during the first 3 months. Holter monitoring appeared to be the most effective and sensitive method of detecting malsensing and should be performed regularly.

[Regional differences in prehospital time delay for patients with acute myocardial infarction; Rotterdam and Groningen, 1990-1995]. / Regionale verschillen in de tijd tot ziekenhuisopname bij patiënten met een acuut myocardinfarct; Rotterdam en Groningen, 1990-1995.

OBJECTIVE: To describe pre-hospital delay times in patients with acute myocardial infarction (AMI) in two regions in the Netherlands: Groningen (a region with high mortality for coronary heart disease (CHD)) and Rotterdam (a region with low CHD mortality). DESIGN: Descriptive. METHOD: The pre-hospital treatment delay of AMI patients in Rotterdam in 1990-1991 versus 1993-1995 was compared and also compared between Groningen en Rotterdam (1993-1995). In each region 3 hospitals participated (1 academic, 2 regional). The data were collected with a structured interview within 7 days after onset of symptoms in hospitalized AMI patients (n = 924) or by interviewing relatives of deceased patients (n = 40). The median patient, general practitioner (GP) and ambulance delays were calculated. RESULTS: Total median pre-hospital delay was 2.5 hours (5-95-percentile: 50 min-36 hours). Median patient delay time was shorter in Groningen than in Rotterdam (respectively 30 and 45 min) and the same applied to doctor delay times (respectively 38 and 72 min). In Rotterdam doctor delay time decreased by 23 min between 1990-1991 and 1993-1995. Median ambulance delay was 30 min in Rotterdam and 35 min in Groningen. Total pre-hospital delay times of self referred patients were 32-78 min shorter than those of patients who consulted a GP before admission. CONCLUSION: Reduction of pre-hospital delay in Rotterdam between 1990-1991 and 1993-1995 was due to faster decision time by the GP. The short pre-hospital treatment delay in Groningen in hospitalized patients suggests that relatively more AMI patients die outside hospital which may contribute to the high CHD mortality in this region.

[The elevation of serum creatine kinase-MB level in trauma patients: misleading impression of myocardial damage]. / Verhoging van de creatinekinase-MB-waarde in serum van traumapatiënten: ten onrechte vermoeden van hartspiercelschade.

OBJECTIVE: To determine the frequency of increase of serum values, not of cardiac origin, of creatine kinase-MB (CK-MB) in trauma patients. DESIGN: Prospective. SETTING: University Hospital, Groningen, the Netherlands. METHODS: 51 trauma patients without chest injury (without myocardial contusion) but with (among others) soft tissue injuries, were included. At admission (time point t1) an ECG and chest X-ray were made and blood was collected for measurement of CK total, CK-MB activity and CK-MB mass. If the CK-MB activity/CK total fraction exceeded 3%, CK electrophoresis was performed. Blood analysis was repeated after 24 hours (t2). RESULTS: CK-MB activity was elevated in 27 patients (53%) at t1 and in 3 (6%) at t2. The fraction CK-MB activity/CK total exceeded 3% in 96% and 33% of these patients at t1 and t2, respectively. In all these cases a CK-BB band was detected by electrophoresis (CK-BB interferes with the CK-MB activity measurement). CK-MB mass was elevated in 11 patients (22%) at t1 and in 19 (37%) at t2. CONCLUSION: CK-MB was frequently elevated in trauma patients owing to skeletal muscle damage and to interference with CK-MB activity measurements. For the detection of myocardial damage in trauma patients, CK-MB measurements are of little use.

Preliminary results of a randomized study on the clinical efficacy of spinal cord stimulation for refractory severe angina pectoris.

For the last 6 years Spinal Cord Stimulation (SCS) has been advocated for patients with therapeutic refractory angina pectoris. We studied the efficacy of spinal cord stimulation on the relief of otherwise intractable angina pectoris in a 2 months' randomized study with 1 year follow-up by quality of life parameters, cardiac parameters and complications. Twenty four patients were randomized to either an actively treated group A (12 patients received the device within a 2 weeks' period) or a control group B (10 patients had an implantation after the study period). In both groups one patient dropped out before the implantation but after the randomization. It is concluded that spinal cord stimulation improves both quality of life and cardiac parameters. The latter included a trend towards reduction in ischaemia after implantation of the device in both treadmill exercise and 24-hour ambulatory Holter recordings, with a concomitant better exercise capacity.

Rate stabilization by right ventricular pacing in patients with atrial fibrillation.

A recent study of de Jongste has demonstrated the lengthening of short R-R intervals in patients with atrial fibrillation by right ventricular pacing. We have further analyzed the data from this study and specifically looked at the effect of right ventricular pacing on the R-R interval instability and heart rate. At the cost of only a slight increase in mean heart rate, a major reduction of the R-R interval instability can be obtained by right ventricular pacing. Based on these findings, we have developed and evaluated an automatic pacing rate algorithm, which continuously varies the stimulation rate in order to stabilize the otherwise irregular rhythm in patients with atrial fibrillation.