Treatment of resistant Raynaud's phenomenon with single-port thoracoscopic sympathicotomy: One-year follow-up.

OBJECTIVE: Follow-up of patients with treatment-resistant Raynaud's phenomenon (RP) one-year after single-port thoracoscopic sympathicotomy (SPTS). METHODS: Eight patients (six males, two females, median age of 45 years) with treatment-resistant RP underwent left-sided SPTS at the third rib (R3), unilaterally. Questionnaires were taken, and number and duration of RP attacks were reported over a 2-week period. Perfusion was assessed with a cooling and recovery procedure at baseline and one year after SPTS. Furthermore, laser speckle contrast analysis, pulse wave velocity, heart rate variability and nailfold capillary microscopy were performed. RESULTS: One year after SPTS the duration of the attacks of was reduced with 1.9 h in the left hand versus 0.3 h in the right hand. Furthermore, three aspects of the questionnaire showed a significant improvement (role limitations due to physical health (p = 0.017), pain (p = 0.027) and physical functioning (p = 0.025)). The total area under the curve of the total cooling and recovery procedure of the left hand was larger one year after surgery (101 (75-140) at baseline versus 118 (95-190) one year post-operatively, p = 0.012), implying a better perfusion in the fingers. This was mainly due to the improvement during the recovery phase (21 (1-41) at baseline versus 38 (24-43) one year post-operatively, p = 0.028). CONCLUSION: One year after unilateral R3 SPTS the benefit with regard to the majority of outcome variables persisted, though some effects seem to attenuate. Long-term effects and long-term follow-up results will be investigated in an on-going study. CLINICAL TRIAL REGISTRATION NUMBER: NCT02680509.

Thoracoscopic sympathicotomy for the treatment of intolerable palmar and axillary hyperhidrosis in children is associated with high recurrence rates.

BACKGROUND: Treatment of palmar and axillary primary focal hyperhidrosis (PFH) in children up to 16 years using thoracoscopic sympathicotomy is supported by scarce evidence. Therefore, this study aimed to summarize the results of our standardized bilateral, one-stage, single-port sympathicotomy (BOSS) in children up to 16 years of age. METHODS: Consecutive children (n = 14) up to 16 years of age undergoing BOSS between October 2011 and June 2015 in our institution were included in this retrospective study. RESULTS: Recurrence of primary hyperhidrosis was noted in seven patients (50.0%), of whom five patients (35.7%) underwent reoperation. Reoperations were associated with placement of additional thoracoscopic ports (n = 1; 12.5%), intraoperative placement of pleural drains (n = 2; 25%), and prolonged air leak (n = 1; 12.5%). Despite the high recurrence and reoperation rates, overall patient satisfaction was high with a median satisfaction score of 7.5 (interquartile range of 1.75; range: 4-9). CONCLUSION: Although the overall patient satisfaction score in our cohort was good, BOSS for the treatment of intolerable palmar and axillary PFH in children up to 16 years of age is associated with a high recurrence and reoperation rate.

Treatment of resistant Raynaud's phenomenon with single-port thoracoscopic sympathicotomy: a novel minimally invasive endoscopic technique.

OBJECTIVE: To assess the minimally invasive single-port thoracoscopic sympathicotomy feasibility and efficacy in patients with treatment-resistant RP. METHODS: Single-port thoracoscopic sympathicotomy was performed unilaterally on the left side in eight patients with RP (six males, two females, with a median age of 45.2 years). Five patients had primary and three had secondary RP. Perfusion effects in the hands were assessed at baseline and after 1 month by using a cooling and recovery procedure, and by using laser speckle contrast analysis. Number and duration of RP attacks were reported over a 2-week period. RESULTS: Patient satisfaction was 100% after surgery. After surgery, a unilateral improvement in perfusion was observed in the left hand compared with the right hand, with cooling and recovery (P = 0.008) and with laser speckle contrast analysis (P = 0.023). In addition, the number and duration of the attacks in the left hand decreased compared with the right hand (both P = 0.028). No serious adverse events occurred in a follow-up period of at least 10 months. CONCLUSION: Single-port thoracoscopic sympathicotomy is feasible and can be effective in improving hand perfusion in patients with RP. However, long-term efficacy needs to be established. CLINICAL TRIAL REGISTRATION NUMBER: NCT02680509.

Heart Rehabilitation in patients awaiting Open heart surgery targeting to prevent Complications and to improve Quality of life (Heart-ROCQ): study protocol for a prospective, randomised, open, blinded endpoint (PROBE) trial.

INTRODUCTION: The rising prevalence of modifiable risk factors (eg, obesity, hypertension and physical inactivity) is causing an increase in possible avoidable complications in patients undergoing cardiac surgery. This study aims to assess whether a combined preoperative and postoperative multidisciplinary cardiac rehabilitation (CR) programme (Heart-ROCQ programme) can improve functional status and reduce surgical complications, readmissions and major adverse cardiac events (MACE) as compared with standard care. METHODS AND ANALYSIS: Patients (n=350) are randomised to the Heart-ROCQ programme or standard care. The Heart-ROCQ programme consists of a preoperative optimisation phase while waiting for surgery (three times per week, minimum of 3 weeks), a postoperative inpatient phase (3 weeks) and an outpatient CR phase (two times per week, 4 weeks). Patients receive multidisciplinary treatment (eg, physical therapy, dietary advice, psychological sessions and smoking cessation). Standard care consists of 6 weeks of postsurgery outpatient CR with education and physical therapy (two times per week). The primary outcome is a composite weighted score of functional status, surgical complications, readmissions and MACE, and is evaluated by a blinded endpoint committee. The secondary outcomes are length of stay, physical and psychological functioning, lifestyle risk factors, and work participation. Finally, an economic evaluation is performed. Data are collected at six time points: at baseline (start of the waiting period), the day before surgery, at discharge from the hospital, and at 3, 7 and 12 months postsurgery. ETHICS AND DISSEMINATION: This study will be conducted according to the principles of the Declaration of Helsinki (V.8, October 2013). The protocol has been approved by the Medical Ethical Review Board of the UMCG (no 2016/464). Results of this study will be submitted to a peer-reviewed scientific journal and can be presented at national and international conferences. TRIAL REGISTRATION NUMBER: NCT02984449.

Depression after myocardial infarction: TNF-α-induced alterations of the blood-brain barrier and its putative therapeutic implications.

Patients experiencing an acute myocardial infarction (AMI) have a three times higher chance to develop depression. Vice versa, depressive symptoms increase the risk of cardiovascular events. The co-existence of both conditions is associated with substantially worse prognosis. Although the underlying mechanism of the interaction is largely unknown, inflammation is thought to be of pivotal importance. AMI-induced peripheral cytokines release may cause cerebral endothelial leakage and hence induces a neuroinflammatory reaction. The neuroinflammation may persist even long after the initial peripheral inflammation has subsided. Among those selected brain regions that are prone to blood-brain barrier dysfunction, the paraventricular nucleus of the hypothalamus (PVN), a major center for cardiovascular autonomic regulation, is indicated to play a mediating role. Optimal cardiovascular therapy improves cardiovascular prognosis without major effects on depression. By the same token, antidepressant therapy in cardiovascular disease is associated with modest improvement in depressive symptoms, however without improvement in cardiac outcome. The failure of current antidepressants and the growing number of patients suffering from both conditions legitimize the search for better antidepressive therapies, from patients as well as society perspectives. Though we appreciate the mutual character of the interaction between depression and AMI, the present review focuses on the side of AMI induced depression and discusses the role of inflammation, represented by the proinflammatory cytokine TNF-α, as potential underlying mechanism. It is conceivable that inhibition of the inflammatory response post-AMI, through targeted anti-inflammatory pharmacotherapeutical agents may prevent the development of depressive symptoms and ultimately may improve cardiovascular outcomes.

Myopathy during statin therapy in the daily practice of an outpatient cardiology clinic: prevalence, predictors and relation with vitamin D.

OBJECTIVE: 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. RESEARCH DESIGN AND METHODS: 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. MAIN OUTCOME MEASURES: Percentage of patients with myopathy in the daily clinical practice of an outpatient clinic, serum 25(OH)D, CK, and predictors of myopathy. RESULTS: 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. CONCLUSIONS: 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.

Multimorbidity, the predominant predictor of quality-of-life, following successful spinal cord stimulation for angina pectoris.

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Subcutaneous electrical nerve stimulation: a feasible and new method for the treatment of patients with refractory angina.

INTRODUCTION: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Basic research models for the study of underlying mechanisms of electrical neuromodulation and ischemic heart-brain interactions.

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.

Spinal cord stimulation in the treatment of refractory angina: systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: The aim of this paper was undertake a systematic review and meta-analysis of the use of spinal cord stimulation (SCS) in the management of refractory angina. METHODS: We searched a number of electronic databases including Medline, Embase and Cochrane Library up to February 2008 to identify randomised controlled trials (RCTs) reporting exercise capacity, ischemic burden, functional class, quality of life, usage of anti-anginal medication, costs and adverse events including mortality. Results were reported both descriptively for each study and using random effects meta-analysis. Given the variety in outcomes reported, some outcome results were pooled as standardised mean differences (SMD) and reported in standard deviation units. RESULTS: Seven RCTs were identified in a total of 270 refractory angina patients. The outcomes of SCS were found to be similar when directly compared to coronary artery bypass grafting (CABG) and percutaneous myocardial laser revascularisation (PMR). Compared to a 'no stimulation' control, there was some evidence of improvement in all outcomes following SCS implantation with significant gains observed in pooled exercise capacity (SMD: 0.76, 0.07 to 1.46, p = 0.03) and health-related quality of life (SMD: 0.83, 95% CI: 0.32 to 1.34, p = 0.001). Trials were small and were judged to range considerably in their quality. The healthcare costs of SCS appeared to be lower than CABG at 2-years follow up. CONCLUSION: SCS appears to be an effective and safe treatment option in the management of refractory angina patients and of similar efficacy and safety to PMR, a potential alternative treatment. Further high quality RCT and cost effectiveness evidence is needed before SCS can be accepted as a routine treatment for refractory angina.

The contribution of observational studies to the knowledge of drug effectiveness in heart failure.

AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Impact of electrical neurostimulation on persistent ST elevation after successful reperfusion by primary percutaneous coronary intervention.

AIMS: 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). METHODS: 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. RESULTS: 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). CONCLUSION: 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.

The effect of electrical neurostimulation on collateral perfusion during acute coronary occlusion.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Electrical neurostimulation induces a significant improvement in the Pw/Pa ratio during acute coronary occlusion.

Incidence and angiographic predictors of collateral function in patients with stable coronary artery disease scheduled for percutaneous coronary intervention.

OBJECTIVES: To investigate the incidence and angiographic predictors of functional collateral perfusion in patients with stable coronary artery disease, scheduled for elective PCI. BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Effectiveness of beta-blocker therapy in daily practice patients with advanced chronic heart failure; is there an effect-modification by age?

AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The effect of beta-blocker therapy on quality of life in heart failure patients: a systematic review and meta-analysis.

PURPOSE: To assess the impact of beta-blocker therapy on quality of life (QoL) in chronic heart failure (CHF) patients receiving optimal standard medication. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.