[Show abstract][Hide abstract] ABSTRACT: The mechanism of statin-related myopathy is unknown, while its prevalence is probably underestimated. An association between statin-related myopathy and vitamin D deficiency has been reported. In this pilot study we assessed the prevalence of myopathy in statin users attending the outpatient clinic of the Department of Cardiology of a University Hospital from October 2009 to March 2010. We also searched for predictors of myopathy and investigated whether the myopathy was associated with vitamin D deficiency.
Statin-treated patients were asked to complete an assisted structured questionnaire. Serum creatine kinase (CK) and 25-hydroxyvitamin D (25(OH)D) were measured. Patients with rheumatic diseases, muscle diseases, (poly)neuropathy and peripheral arterial disease were excluded from predictor analysis.
Percentage of patients with myopathy in the daily clinical practice of an outpatient clinic, serum 25(OH)D, CK, and predictors of myopathy.
One hundred and four statin-treated patients completed the questionnaire. Serum 25(OH)D was measured in 93 patients. Twenty patients with confounding comorbidities were excluded from analysis. Of the remaining 84 patients, 33% reported myopathy, 24% had myalgia and 6% myositis. Rhabdomyolysis was not observed. Time spent outdoors during winter (≤6 h/week; OR: 10.61; 95% CI: 1.91-58.88), total number of prescribed drugs (1.39; 1.05-1.83), BMI (1.35; 1.07-1.69), CK (1.02; 1.00-1.03) and consumption of fish (≥1/week; 0.19; 0.04-0.89) were predictors of myopathy in multivariate analysis.
Considering the small patient group and a relatively narrow range of vitamin D levels, we arrive at the following statements: 1) one out of three patients reported myopathy; 2) BMI, CK, number of prescription drugs, time spent outdoors and fish consumption were myopathy predictors; and 3) myopathy and 25(OH)D were unrelated.
Current Medical Research and Opinion 06/2012; 28(7):1247-52. DOI:10.1185/03007995.2012.702102 · 2.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Patients suffering from chronic angina pectoris, insufficiently controllable with medication and revascularization, are an increasing medical and psychosocial problem. Although spinal cord stimulation (SCS) is proven to employ, safe, long-term anti-angina, and anti-ischemic effects for these patients, the use of SCS in this group remains limited. The reason for this restricted use is largely unknown. However, among other reasons, it may be related to the difficulties in positioning an electrode in the epidural space. We studied the feasibility and efficacy of subcutaneous implantation of an entire system.
Seven male patients, mean age 67 ± 3.6 years, received complete subcutaneously implanted electrical nerve stimulation (SENS) systems, with one or more leads fixed in parallel with the sternum, covering the angina area. At baseline and 2 months follow-up patients performed exercise and quality of life tests (Seattle Angina Questionnaire and diaries number angina attacks and glyceryl trinitrate use).
All patients showed clinical relevant improvement (baseline vs. follow-up), in exercise (63%) and quality of life (Seattle Angina Questionnaire 59%). The number of angina attacks dropped 82% and the number of glyceryl trinitrate use decreased by 90%. No major adverse events were observed.
This small feasibility study demonstrates SENS to be an effective and safe method to treat patients suffering from refractory angina. Furthermore, SENS is less invasive and appears to have less lead migrations compared with SCS.
[Show abstract][Hide abstract] ABSTRACT: Patients suffering from severe chronic angina pectoris (AP) that has become therapeutically refractory to medication and revascularization can be adequately treated with spinal cord stimulation (SCS). However, following SCS implantation for angina, not all patients show a consistent improvement in quality of life (QoL). Therefore, we sought to study the association of baseline characteristics and chronic multimorbidities on QoL following SCS implantation.
All patients treated with SCS for refractory AP (rAP) were registered in a local data base. Patients who had discontinued SCS therapy were excluded from further analysis. Baseline characteristics, such as exercise limiting morbidities (chronic obstructive pulmonary disease [COPD], rheumatic disease, diabetes mellitus [DM], obesity expressed as body mass index [BMI]>25) and demographic data, were retrieved from the data base. QoL was studied using the Seattle Angina Questionnaire and the RAND-36 questionnaire.
During a 21-year registration period (1986-2008), we enlisted 127 patients with SCS for rAP in our data base. Eighty-two, of whom 59 died, had discontinued SCS and were lost to follow-up. Out of the remaining 45 patients, 33 returned their questionnaires (73.3%). At SCS implantation, 72.7% of the patients were male, mean age 58±8.5 years. Twenty-four patients were in class III-IV angina and nine in class II-III NYHA. After a follow-up of 6.4±4.1 years, men had better physical capacity and experienced less impairment in QoL resulting from physical or emotional restrictions (all p<0.05) compared with women. Patients without COPD reported a better general health compared with those with rAP and COPD (p<0.05). The association of DM on QoL was borderline significant. Patients with lower BMI scored better on emotional well-being and perception of disease than those with a higher BMI (p<0.05 and p<0.05, respectively). None of the patients reported other morbidities limiting their exercise.
Men showed a larger improvement in QoL following SCS implantation, compared with women. As SCS improves rAP, other chronic morbidities such as COPD, DM, and BMI may become the limiting factors for exercise and subsequently adversely affect QoL following implantation of an SCS system. As a consequence of the present relatively small single-center study, we recommend studies regarding rAP and SCS to also address the effect of comorbidities on outcomes.
[Show abstract][Hide abstract] ABSTRACT: The study of mechanisms of action underlying the use of electrical neuromodulation for angina and myocardial ischemia may illuminate heart-brain interactions that influence these conditions. To investigate these mechanisms of action, we initiated a neurocardiology program in the 1990s. This review discusses the experimental models we have studied to unravel the heart-brain interactions involved in the use of electrical neuromodulation for ischemic disease.
Cleveland Clinic Journal of Medicine 05/2009; 76 Suppl 2:S41-6. DOI:10.3949/ccjm.76.s2.09 · 2.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This chapter focuses on the use of spinal cord stimulation (SCS) for treating refractory angina. The modern concept for angina pectoris is that during either physical or mental stress, in the presence of an atherosclerotic narrowing in one or more coronary arteries, oxygen supply soon becomes insufficient for the myocardial needs since the stenotic coronary arteries are not capable of dilating sufficiently in order to meet the increased oxygen demand. Electrical neuromodulation is suggested to those patients who suffer from disabling chest pain resulting from coronary artery disease, have reversible myocardial ischemia, are unresponsive to pharmacotherapy, and are not candidates for revascularization. The standard procedure for SCS for angina is performed under local anesthesia. Local anesthesia is essential to the success of this operation because the surgeon places the electrodes of the SCS system into the epidural space and moves and activates the electrodes until the awake patient perceives stimulation paresthesiae concordant to the area of their perceived pain. To ensure the long-term benefit of neuromodulation, an interdisciplinary team consisting of the patient's physician, cardiologists, cardiac interventionalists, and cardiothoracic surgeons is suggested. The day after implantation of the SCS system, the programmed settings of the system are adjusted to optimize battery longevity while providing concordant stimulation paresthesia. In order to optimize longevity of the battery, in conjunction with providing optimal results, the upper and lower limits of the device are set at the lowest comfortable limits for the patient. Though electrical neuromodulation is a reversible therapy, as in all implanted SCS devices, complications during and following the implantation may occur, such as loss of paresthesiae, lead dislodgment, and infections. The implantation of an SCS in a patient whose life depends on a bradycardia pacemaker or on an implantable cardioverter defibrillator (ICD) is not considered to be safe, even if essential precautions have been taken.
[Show abstract][Hide abstract] ABSTRACT: To study the effect of electrical neurostimulation on the ST segment shift in patients with ST elevation myocardial infarction (STEMI) with residual ST elevation after primary percutaneous coronary intervention (PCI).
After primary PCI, 38 patients with STEMI were divided into 2 groups. Group 1 received 15 minutes of active neurostimulation after the baseline electrocardiogram (ECG); group 2 received 15 minutes of active neurostimulation after 15 minutes of nonactive neurostimulation.
In group 1, ST elevation decreased with neurostimulation from 0.65 +/- 0.56 to 0.55 +/- 0.51 (P = .02) and to 0.50 +/- 0.52 (P = .01) without electrical neurostimulation. In group 2, ST elevation changed without neurostimulation from 0.37 +/- 0.32 to 0.33 +/- 0.30 (P = NS) and to 0.28 +/- 0.27 (P = .01) with electrical neurostimulation. In a posthoc analysis, 17 responders had higher ST elevation at the ECG before active electrical neurostimulation than 21 nonresponders (P = .001).
Electrical neurostimulation may result in significant additional reduction of ST elevation in STEMI after reperfusion treatment, in particular in patients with marked ST elevation on the first ECG after successful primary PCI.
Journal of electrocardiology 11/2007; 40(6):522-6. DOI:10.1016/j.jelectrocard.2007.05.014 · 1.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Randomized controlled trials (RCTs) are the golden standard for the assessment of drug efficacy. Little is known about the add-on value of observational studies in heart failure (HF). We aimed to assess the contribution of observational studies to actual knowledge regarding the effectiveness of angiotensin-converting enzyme inhibitors (ACEI), and beta-blockers (BB) in HF.
Observational studies that assessed the effectiveness of ACEI and BB in HF were identified by searching Medline, Embase, Cochrane Database (1990-2005) and the bibliographies of published articles. Cohort, case-control and time-series analysis studies were considered for inclusion. Studies with <100 patients and those who did not perform a multivariate analysis were excluded.
A total of 23 cohort studies met the inclusion criteria. Studies of ACEI and BB showed a decrease in mortality with drug use in elderly patients with a broad range of ejection fraction (EF), and in those with depressed EF. Additionally, they showed a decrease in mortality in patients with renal insufficiency. The effect of ACEI and BB in HF with preserved EF was not clear, although last evidence suggests a potential benefit. Low-dose ACEI and BB may have beneficial effects. Target doses of ACEI seemed superior to low doses, but there was no clear dose-response relationship.
Observational studies in HF validate the effectiveness of ACEI and BB in populations underrepresented or excluded from RCTs. Observational studies of drug effectiveness provide relevant additional information for clinical practice.
British Journal of Clinical Pharmacology 11/2007; 64(4):406-14. DOI:10.1111/j.1365-2125.2007.03010.x · 3.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background. Patients with unstable angina pectoris may become refractory to conventional therapies. Electrical neurostimulation with transcutaneous electrical stimulation and/or spinal cord stimulation has been shown to be effective for patients with refractory unstable angina pectoris in hospital settings. Our aim was to investigate the effects of electrical neurostimulation on outcomes of unstable angina after hospital discharge, in terms of hospital re-admission rates and long-term survival analysis.
Method. Twenty-seven consecutive patients with unstable angina pectoris, refractory to conventional therapies, received electrical neurostimulation in a tertiary referral hospital. We studied the number of hospital admissions in the year before when compared to the first year after electrical neurostimulation and performed survival analysis of the group.
Results. Twenty-six patients had beneficial effects of electrical neurostimulation during their admission to the hospital. During a mean follow-up of 6.6 ± 4.1 years, electrical neurostimulation was still effective in 21 out of 26. In 11 patients with previous hospital admissions, the number of hospital admissions decreased significantly after electrical neurostimulation (p = 0.007). The combined mortality and (re)infarction rate after one-year follow-up was 14%.
Conclusion. The results of this observational study show long-term beneficial effects of electrical neurostimulation in a population of patients with unstable refractory angina. Therefore, electrical neurostimulation should be considered as a beneficial treatment for patients with unstable angina pectoris, refractory to conventional therapies.
[Show abstract][Hide abstract] ABSTRACT: To investigate the incidence and angiographic predictors of functional collateral perfusion in patients with stable coronary artery disease, scheduled for elective PCI.
Functional collateral perfusion is defined as a Pw/Pa ratio>or=0.24. Since this can only be measured intracoronary, it is important to investigate baseline clinical and angiographic predictors for functional collateral perfusion.
Collateral perfusion was measured during balloon inflation, with the use of a pressure-monitoring guide wire. Baseline clinical and angiographic characteristics were analyzed and collateral grading was done according to Rentrop's classification for coronary angiograms.
Functional collateral perfusion was found in 40 of the 89 patients (45%). Angiographic signs of collaterals (Rentrop>or=1) were present in 15 of the 89 patients. Of the 40 patients with the functional collateral perfusion 11 patients (28%) had Rentrop>or=1; of the 49 patients without functional collaterals there were 4 patients with Rentrop>or=1 (8%) (P=0.02). There were no significant differences in baseline clinical characteristics or in other angiographic characteristics.
In patients with stable coronary artery disease scheduled for elective PCI, 45% have functional collaterals. Rentrop's angiographic classification can be used to predict the presence or absence of functional collaterals, however with a rather modest positive and negative predictive value.
[Show abstract][Hide abstract] ABSTRACT: To assess the long-term efficacy of neurostimulation for treating refractory angina pectoris-like chest pain, we followed patients, treated with either transcutaneous electrical nerve stimulation (TENS) or spinal cord stimulation (SCS).
Neurostimulation was judged successful and subsequently continued when initial pain was reduced at least 50%. All patients started with TENS, but if skin irritation occurred during TENS, a SCS system was implanted. The quality of life was measured at baseline and follow-up with the Seattle Angina Questionnaire. Additional information was gathered concerning anti-anginal medication, complaints, and physical condition.
Of 36 patients treated successfully with neurostimulation, we identified 24 patients after a mean (SD) follow-up period of 5.08 (3.86) years; 12 patients dropped out of the study. In 13 of the remaining 24 patients, TENS induced skin irritation. Eight of these 13 patients received successful SCS, while five refused implantation. In the 24 patients, a mean pain reduction of 57% was achieved in conjunction with an increased exercise capacity of 30% and walking distance increased from 0.73 (0.83) to 1.62 (1.62) (p=0.018). Within the Seattle Angina Questionnaire the domain 'disease perception' improved from 38.89 (16.61) to 49.31 (21.83) (p=0.004), the domain 'physical limitation' improved from 29.89 (15.10) to 40.97 (22.63) (p=0.001) and 'anginal frequency' improved from 41.67 (24.08) to 55.00 (23.03) (p=0.005). In addition, nitroglycerin consumption was reduced from 7.85 (8.49) to 1.98 (2.19) (p=0.001).
Neurostimulation techniques should thus be of widespread value for treating angina pectoris-like chest pain in patients who are refractory to medication.
European Journal of Pain 05/2007; 11(3):360-5. DOI:10.1016/j.ejpain.2006.04.002 · 2.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The effects of beta-blockers in daily practice patients with advanced chronic heart failure (CHF) and a broad range of ejection fraction (EF) are not well established. We aimed to assess, first, the association between beta-blocker prescription at discharge and mortality in a cohort of patients with advanced CHF, and second, whether this association is modified by the age of the patient.
Patients diagnosed with advanced CHF (n = 625) were prospectively followed after discharge from the Cardiology Department. The mean age was 76 years, 53% male, mean EF 42 +/- 16%. Overall, 308 (49%) patients had a beta-blocker prescribed at discharge, 140 (22%) low-dose and 168 (27%) high-dose therapy. We used multivariate Cox analysis to assess the association between beta-blocker use at discharge and mortality.
After a mean follow-up of 22 months, 117 (27%) patients died. Prescription of a beta-blocker was associated with a 45% relative risk reduction (hazard ratio 0.55, 95% confidence interval 0.39, 0.78). The relative risk reduction was similar with low and high doses of beta-blockers (42% and 49%). However, the relative risk reduction was higher in younger than in older patients (P = 0.006). In patients < or = 75 years old prescription of a beta-blocker was associated with 71% risk reduction, whereas in patients >75 years old it was associated with 21% risk reduction.
In this daily practice cohort of patients with advanced CHF, prescription of a beta-blocker was associated with significant mortality reduction. However, the beneficial effects of beta-blockers appear to be greater in younger patients.
British Journal of Clinical Pharmacology 04/2007; 63(3):356-64. · 3.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The effects of β-blockers in daily practice patients with advanced chronic heart failure (CHF) and a broad range of ejection fraction (EF) are not well established. We aimed to assess, first, the association between β-blocker prescription at discharge and mortality in a cohort of patients with advanced CHF, and second, whether this association is modified by the age of the patient.
Patients diagnosed with advanced CHF (n = 625) were prospectively followed after discharge from the Cardiology Department. The mean age was 76 years, 53% male, mean EF 42 ± 16%. Overall, 308 (49%) patients had a β-blocker prescribed at discharge, 140 (22%) low-dose and 168 (27%) high-dose therapy. We used multivariate Cox analysis to assess the association between β-blocker use at discharge and mortality.
After a mean follow-up of 22 months, 117 (27%) patients died. Prescription of a β-blocker was associated with a 45% relative risk reduction (hazard ratio 0.55, 95% confidence interval 0.39, 0.78). The relative risk reduction was similar with low and high doses of β-blockers (42% and 49%). However, the relative risk reduction was higher in younger than in older patients (P = 0.006). In patients ≤75 years old prescription of a β-blocker was associated with 71% risk reduction, whereas in patients >75 years old it was associated with 21% risk reduction.
In this daily practice cohort of patients with advanced CHF, prescription of a β-blocker was associated with significant mortality reduction. However, the beneficial effects of β-blockers appear to be greater in younger patients.
British Journal of Clinical Pharmacology 03/2007; 63(3):356-364. DOI:10.1111/j.1365-2125.2006.02769.x · 3.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The effects of beta-blockers in patients with heart failure (HF) and preserved left ventricular ejection fraction (LVEF) are not well established.
To assess the association between beta-blocker prescription at discharge and mortality in a cohort of patients with advanced HF and preserved LVEF.
We prospectively studied a cohort of 443 patients with advanced HF and preserved LVEF (LVEF> or =40%). Mean age was 78 years, 56% female, 33% NYHA class IV. Overall, 227 patients (51%) had a beta-blocker prescribed at discharge. Mean duration of follow-up was 25 (+/-18) months. Death (all cause) occurred in 40 patients (17.6%) who were receiving a beta-blocker at discharge and 73 patients (33.8%) who were not on a beta-blocker. In multivariate Cox analysis, including adjustment for propensity score, prescription of a beta-blocker remained associated with a 43% relative mortality risk reduction (HR 0.57, 95% CI 0.37 to 0.88, p=0.01).
In this cohort of patients with advanced HF and preserved LVEF, prescription of a beta-blocker was associated with a significant mortality reduction. This beneficial effect of beta-blocker use needs to be further confirmed in prospective, randomised clinical trials.
European Journal of Heart Failure 03/2007; 9(3):280-6. DOI:10.1016/j.ejheart.2006.07.008 · 6.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Electrical neurostimulation can be used to treat patients with refractory angina, it reduces angina and ischemia. Previous data have suggested that electrical neurostimulation may alleviate myocardial ischaemia through increased collateral perfusion. We investigated the effect of electrical neurostimulation on functional collateral perfusion, assessed by distal coronary pressure measurement during acute coronary occlusion. We sought to study the effect of electrical neurostimulation on collateral perfusion.
Sixty patients with stable angina and significant coronary artery disease planned for elective percutaneous coronary intervention were split in two groups. In all patients two balloon inflations of 60 seconds were performed, the first for balloon dilatation of the lesion (first episode), the second for stent delivery (second episode). The Pw/Pa ratio (wedge pressure/aortic pressure) was measured during both ischaemic episodes. Group 1 received 5 minutes of active neurostimulation before plus 1 minute during the first episode, group 2 received 5 minutes of active neurostimulation before plus 1 minute during the second episode.
In group 1 the Pw/Pa ratio decreased by 10 +/- 22% from 0.20 +/- 0.09 to 0.19 +/- 0.09 (p = 0.004) when electrical neurostimulation was deactivated. In group 2 the Pw/Pa ratio increased by 9 +/- 15% from 0.22 +/- 0.09 to 0.24 +/- 0.10 (p = 0.001) when electrical neurostimulation was activated.
Electrical neurostimulation induces a significant improvement in the Pw/Pa ratio during acute coronary occlusion.
[Show abstract][Hide abstract] ABSTRACT: To assess the impact of beta-blocker therapy on quality of life (QoL) in chronic heart failure (CHF) patients receiving optimal standard medication.
Randomised controlled trials (RCT) assessing QoL with a generic or disease specific instrument were identified by searching Medline, Embase, Pascal, Cochrane Controlled Trial database, and the bibliographies of the published articles. Studies published between 1985 and 2002 were included, regardless of language of publication. Cochrane Review Manager 4.2 software was used to analyse the data and standardised mean difference (SMD) was calculated to assess the effect on QoL.
A total of 9 trials involving 1954 patients fit into the inclusion criteria for the analysis. QoL improved more in the beta-blocker group compared to the control arm, but the SMD did not reach statistical significance (SMD, 0.07; 95%CI [-0.16, 0.02]; p = 0.13). Subgroup analysis, per type of beta-blocker and various treatment follow-up showed similar results.
In this meta-analysis there is evidence that beta-blocker therapy, on top of standard medication, does not impair QoL. Clinicians may add beta-blockers to standard therapy without concerns of impairing QoL in patients with CHF.
Pharmacoepidemiology and Drug Safety 02/2007; 16(2):152-9. DOI:10.1002/pds.1234 · 2.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Our objective was to determine whether electrical neuromodulation using spinal cord stimulation (SCS) mitigates transient ischemia-induced ventricular infarction and, if so, whether adrenergic neurons are involved in such cardioprotection. The hearts of anesthetized rabbits, subjected to 30 min of left anterior descending coronary arterial occlusion (CAO) followed by 3 h of reperfusion (control), were compared with those with preemptive SCS (starting 15 min before and continuing throughout the 30-min CAO) or reactive SCS (started at 1 or 28 min of CAO). For SCS, the dorsal C8-T2 segments of the spinal cord were stimulated electrically (50 Hz, 0.2 ms, 90% of motor threshold). For preemptive SCS, separate groups of animals were pretreated 15 min before SCS onset with 1) vehicle, 2) prazosin (alpha(1)-adrenoceptor blockade), or 3) timolol (beta-adrenoceptor blockade). Infarct size (IS), measured with tetrazolium, was expressed as a percentage of risk zone. In controls exposed to 30 min of CAO, IS was 36.4 +/- 9.5% (SD). Preemptive SCS reduced IS to 21.8 +/- 6.8% (P < 0.001). Preemptive SCS-mediated infarct reduction was eliminated by prazosin (36.6 +/- 8.8%) and blunted by timolol (29.4 +/- 7.5%). Reactive SCS did not reduce IS. SCS increased phosphorylation of cardiac PKC. SCS did not alter blood pressure or heart rate. We conclude that preemptive SCS reduces the size of infarcts induced by transient CAO; such cardioprotection involves cardiac adrenergic neurons.
[Show abstract][Hide abstract] ABSTRACT: The combination of angina pectoris, angiographically normal coronary arteries, and a positive exercise stress test (EST) is referred to as cardiac syndrome X. However, a large group of patients suspected of syndrome X reveals a normal exercise stress test and weakens the diagnosis of syndrome X. Previous studies demonstrated an impaired coronary flow reserve on ammonia positron emission tomography (PET) in patients with syndrome X.
To evaluate the coronary flow reserve in patients suspected of syndrome X with positive and negative EST findings, using [(13)N]ammonia PET as the diagnostic aid.
Forty-two patients with chest pain and a normal coronary angiography, were analysed by exercise stress testing (EST) and the dypyridamole stress test (DST) on [(13)N]ammonia PET. Two subgroups were predefined, based on outcome of EST: an EST positive and negative group. A normal control group was used as the reference method.
A total of 24 (57%) out of 42 patients had significant ST-T changes (EST positive). [(13)N]ammonia PET showed a significantly lower rest flow in the EST positive and EST negative group compared to controls (P<0.001 and P=0.0028, respectively). DST [(13)N]ammonia PET perfusion was significantly reduced in flow in both the EST positive and EST negative groups (P<0.001 both), as was the DST/rest [(13)N]ammonia perfusion reserve (P<0.001 for both), compared to normal controls.
PET demonstrates a reduced coronary flow reserve in patients suspected of syndrome X, irrespective of the EST findings.
Nuclear Medicine Communications 10/2006; 27(10):791-4. DOI:10.1097/01.mnm.0000237984.46844.42 · 1.67 Impact Factor