Risk prediction in stable angina pectoris.

BACKGROUND: Although stable angina pectoris often carries a favourable prognosis, it remains important to identify patients with an increased risk of cardiovascular (CV) complications. Many new markers of disease activity and prognosis have been described. We evaluated whether common and easily accessible markers in everyday care provide sufficient prognostic information. MATERIALS AND METHODS: The Angina Pectoris Prognosis Study in Stockholm treated 809 patients (248 women) with stable angina pectoris with metoprolol or verapamil double blind during a median follow-up of 3·4 years, with a registry-based extended follow-up after 9·1 years. Clinical and mechanistic variables, including lipids and glucose, renal function, ambulatory and exercise-induced ischaemia, heart rate variability, cardiac and vascular ultrasonography, and psychosocial variables were included in an integrated analysis. Main outcome measures were nonfatal myocardial infarction (MI) and CV death combined. RESULTS: In all, 139 patients (18 women) suffered a main outcome. Independent predictive variables were (odds ratio [95% confidence intervals]), age (1·04 per year [1·00;1·08], P = 0·041), female sex (0·33 [0·16;0·69], P = 0·001), fasting blood glucose (1.29 per mM [1.14; 1.46], P < 0·001), serum creatinine (1·02 per µM [1·00;1·03], P < 0·001) and leucocyte counts (1·21 per 10(6)  cells/L [1·06;1·40], P = 0·008). Smoking habits, lipids and hypertension or a previous MI provided limited additional information. Impaired fasting glucose was as predictive as manifest diabetes and interacted adversely with serum creatinine. Sexual problems were predictive among men. CONCLUSIONS: Easily accessible clinical and demographic variables provide a good risk prediction in stable angina pectoris. Impaired glucose tolerance and an elevated serum creatinine are particularly important.

Frequency of serious complications after surgery for snoring and sleep apnea.

CONCLUSION: No case of death related to surgery in the form of uvulopalatopharyngoplasty, uvulopalatoplasty or nasal surgery for snoring or sleep apnea has been recorded in Sweden among 4876 patients treated between 1997 and 2005. Severe complications of surgery in the peri- and postoperative period, especially in the form of bleedings and infections, were most common after uvulopalatopharyngoplasty, occurring in 3.7%. OBJECTIVE: To investigate the frequency of serious complications, including death, of surgery for treatment of snoring and sleep apnea. METHODS: All Swedish adults who were treated surgically because of snoring or sleep apnea from January 1997 to December 2005 were identified in the National Patient Register. Mortality and serious complications within 30 days from surgery were obtained from the National Cause of Death Register and the National Patient Register. RESULTS: A total of 4876 patients were treated surgically. Uvulopalatopharyngoplasty was performed in 3572 patients, uvulopalatoplasty in 929 patients, and nasal surgery in 375 patients. None of the surgically treated patients died in the peri- and postoperative period. Severe complications, mainly bleedings and infections, were recorded in 37.1 per 1000 patients treated with uvulopalatopharyngoplasty, in 5.6 per 1000 patients after uvulopalatoplasty, and in 8.8 per 1000 patients after nasal surgery.

Toward a new information infrastructure in health technology assessment: communication, design, process, and results.

OBJECTIVES: The aim of this study was to facilitate effective internal and external communication of an international network and to explore how to support communication and work processes in health technology assessment (HTA). STRUCTURE AND METHODS: European network for Health Technology Assessment (EUnetHTA) connected sixty-four HTA Partner organizations from thirty-three countries. User needs in the different steps of the HTA process were the starting point for developing an information system. A step-wise, interdisciplinary, creative approach was used in developing practical tools. RESULTS: An Information Platform facilitated the exchange of scientific information between Partners and with external target groups. More than 200 virtual meetings were set up during the project using an e-meeting tool. A Clearinghouse prototype was developed with the intent to offering a single point of access to HTA relevant information. This evolved into a next step not planned from the outset: Developing a running HTA Information System including several Web-based tools to support communication and daily HTA processes. A communication strategy guided the communication effort, focusing on practical tools, creating added value, involving stakeholders, and avoiding duplication of effort. CONCLUSIONS: Modern technology enables a new information infrastructure for HTA. The potential of information and communication technology was used as a strategic tool. Several target groups were represented among the Partners, which supported collaboration and made it easier to identify user needs. A distinctive visual identity made it easier to gain and maintain visibility on a limited budget.

European network for health technology assessment, EUnetHTA: planning, development, and implementation of a sustainable European network for health technology assessment.

OBJECTIVES: The European network on Health Technology Assessment (EUnetHTA) aimed to produce tangible and practical results to be used in the various phases of health technology assessment and to establish a framework and processes to support this. This article presents the background, objectives, and organization of EUnetHTA, which involved a total of sixty-four partner organizations. METHODS: Establishing an effective and sustainable structure for a transnational network involved many managerial, policy, and methodological tools, according to the objective of each task or Work Package. Transparency in organization, financial transactions, and decision making was a key principle in the management of the Project as was the commitment to appropriately involve stakeholders. RESULTS: EUnetHTA activities resulted in a clear management and governance structure, efficient partnership, and transnational cooperation. The Project developed a model for sustainable continuation of the EUnetHTA Collaboration. CONCLUSIONS: The EUnetHTA Project achieved its goals by producing a suite of practical tools, a strong network, and plans for continuing the work in a sustainable EUnetHTA Collaboration that facilitates and promotes the use of HTA at national and regional levels. Responsiveness to political developments in Europe should be balanced with maintaining a high level of ambition to promote independent, evidence-based information and well-tested tools for best practice based on a strong network of HTA institutions.

Long-term stability of heart rate variability in chronic stable angina pectoris, and the impact of an acute myocardial infarction.

BACKGROUND: Heart rate variability (HRV) reflects the balance between cardiac parasympathetic and sympathetic autonomic influences. Reduced HRV has adverse prognostic implications. The time course for changes in HRV over prolonged periods of time and the influence of an acute coronary event on HRV are not well established. METHODS: Heart rate variability was assessed in patients with chronic stable angina pectoris, who were followed for 3 years within the Angina Prognosis Study in Stockholm. Patients who suffered an acute myocardial infarction after the study were re-examined after this event. We assessed HRV by the simple geometric method differential index, and traditional time- and frequency-domain measurements of HRV. RESULTS: The differential index was essentially unchanged during the study (i.e. the ratio month 36/month 1 was 1.00 +/- 0.06, n = 261). Also most other time and frequency indices of HRV (SDNN, r-MSSD, SDNNIDX, total power, and VLF, LF, HF respectively; n = 63) remained largely unchanged; pNN50 and LF/HF were, however, less reproducible. In 21 patients with a subsequent acute myocardial infarction, SDNN, SDNNIDX, total power, LF and LF/HF were reduced following the event, whereas differential index, pNN50 and HF remained unchanged. CONCLUSIONS: Differential index and other indices of HRV are stable and reproducible in patients with chronic stable angina pectoris. High-frequency HRV (reflecting cardiac parasympathetic activity) and the differential index changed little following an acute coronary event, and may be suitable for predictions of the future risk of sudden death even in the presence of a recent acute coronary event.

Effects and side-effects of surgery for snoring and obstructive sleep apnea--a systematic review.

STUDY OBJECTIVES: Many patients undergo surgery for snoring and sleep apnea, although the efficacy and safety of such procedures have not been clearly established. Our aim was systematically to review studies of the efficacy and adverse effects of surgery for snoring and obstructive sleep apnea. DESIGN: Systematic review. MEASUREMENTS: PubMed and Cochrane databases were searched in September 2007. Randomized controlled trials of surgery vs. sham surgery or conservative treatment in adults, with daytime sleepiness, quality of life, apnea-hypopnea index, and snoring as outcomes were included. Observational studies were also reviewed to assess adverse effects. Evidence of effect required at least two studies of medium and high quality reporting the same result. RESULTS: Four studies of benefits and 45 studies of adverse effects were included. There was no significant effect on daytime sleepiness and quality of life after laser-assisted uvulopalatoplasty and radiofrequency ablation. The apnea-hypopnea index and snoring was reduced in one trial after laser-assisted uvulopalatoplasty but not in another trial. Subjective snoring was reduced in one trial after radiofrequency ablation. No trial investigating the effect of any other surgical modality met the inclusion criteria. Persistent side-effects occurred after uvulopalatopharyngoplasty and uvulopalatoplasty in about half the patients and difficulty in swallowing, globus sensation and voice changes were especially common. CONCLUSIONS: Only a small number of randomized controlled trials with a limited number of patients assessing some surgical modalities for snoring or sleep apnea are available. These studies do not provide any evidence of effect from laser-assisted uvulopalatoplasty or radiofrequency ablation on daytime sleepiness, apnea reduction, quality of life or snoring. We call for research of randomized, controlled trials of surgery other than uvulopalatopharyngoplasty and uvulopalatoplasty, as they are related to a high risk of long-term side-effects, especially difficulty swallowing.

Differential index: a simple time domain heart rate variability analysis with prognostic implications in stable angina pectoris.

OBJECTIVES: To examine the usefulness of time domain heart rate variability (HRV) measurements by a simple graphical method, the differential index (DI), in prognostic assessments of patients with chronic stable angina pectoris. METHODS: HRV measurements in the time domain by DI were compared to conventional measurements of standard deviation of all normal-to-normal intervals (SDNN), percent of differences between adjacent normal RR intervals >50 ms (PNN50) and square root of the mean of the sum of squares of differences between adjacent normal RR intervals (RMSSD) from 24-hour ambulatory electrocardiographic recordings in 678 patients in the Angina Prognosis Study in Stockholm. The patients received double-blind treatment with metoprolol or verapamil. Main outcome measures were cardiovascular death or non-fatal myocardial infarction during follow-up (median 40 months). RESULTS: Patients suffering cardiovascular death (n = 30) had lower DI, SDNN and PNN50 (all p < 0.001). In a multivariate Cox model, DI below median independently predicted cardiovascular death (p = 0.002), as did SDNN (p = 0.016) and PNN50 (p = 0.030), but not RMSSD (p = 0.10). The separation of survival curves was most pronounced and specificity was slightly better with DI. DI and PNN50 increased with metoprolol but not verapamil treatment. Short-term treatment effects were not related to prognosis. CONCLUSIONS: Low time domain HRV carries independent prognostic information regarding cardiovascular death in stable angina pectoris. The simple DI method provided equally good or better prognostic information than conventional, more laborious HRV methods.

Differential index, a novel graphical method for measurements of heart rate variability.

BACKGROUND: Commonly used methods to evaluate heart rate variability require extensive filtering of the registrations in order to exclude artefacts and ectopic beats. We developed and validated a novel graphical method for time-domain measurements of heart rate variability, the differential index, which does not require filtering and is simple to use. METHODS: The 24-h ambulatory long-term electrocardiogram recordings from 120 patients with angina pectoris and 49 control subjects were computerised without any filtering process. Sample density histograms of differences in the RR interval for successive beats were constructed and the widths of the histograms were used to obtain the differential index. For comparison, the same registrations were analysed by conventional methods. RESULTS: The differential index was most closely related (P<0.001) to conventional short-term time domain (e.g. percent of differences between adjacent normal RR intervals >50 ms, pNN50, r=0.81) and frequency-domain (e.g. high frequency power, r=0.84) components, but also to long-term time domain (e.g. standard deviation of all normal-to-normal RR intervals for all 5-min segments of the entire registration, SDNNIDX, r=0.72) and frequency-domain (e.g. low frequency power, r=0.64) components. CONCLUSION: The differential index method shows good agreement with established indices of heart rate variability. The insensitivity to recording artefacts and short-lasting disturbances of sinus rhythm make the differential index method particularly suited when data quality is imperfect. The simplicity of the method is valuable when large numbers of registrations are to be evaluated.

Is left ventricular diastolic function an independent marker of prognosis after acute myocardial infarction?

BACKGROUND: In addition to clinical risk markers, indices of left ventricular (LV) systolic function are valuable prognostic markers after acute myocardial infarction (MI). Previous studies have also suggested that LV diastolic function may contribute with prognostic information. The present study assessed whether this assumption applies to a large population of patients with acute MI who underwent thrombolytic therapy. METHODS AND RESULTS: 520 out of 608 patients participating in the ATTenuation by Adenosine of Cardiac Complications (ATTACC) study, with an ST-elevation acute MI underwent two-dimensional and Doppler echocardiographic examination at 4 (range 2-10) days after admission. During the follow-up period of 31 (S.D. +/- 11) months, cardiovascular death occurred in 57 (11%) patients, nonfatal acute MI occurred in 77 (15%), and 124 (24%) patients suffered a combined cardiovascular end-point (either nonfatal acute MI or cardiovascular death). Univariate regression analysis showed that all indices of LV systolic function predicted cardiovascular death and combined cardiovascular end-points. Regarding LV diastolic function only a restrictive filling pattern predicted cardiovascular death. In a multistep multivariate regression analysis in which the variables were introduced in a hierarchic order age, history of systemic hypertension, wall motion score index (WMSi), and history of previous MI and diabetes mellitus were independent predictors of cardiovascular death. A history of systemic hypertension or congestive heart failure were independent predictors of nonfatal acute MI, while a history of systemic hypertension, wall motion score index and diabetes mellitus independently predicted combined cardiovascular end-points. CONCLUSIONS: The results of this study confirmed that clinical risk indicators and LV systolic function were the most important independent predictors of cardiovascular death and combined cardiovascular end-points. LV diastolic function assessed by Doppler-echocardiography did not provide additional prognostic information.