Non-fatal cardiovascular outcome in patients with posttraumatic stress symptoms caused by myocardial infarction

Objectives Posttraumatic stress disorder (PTSD) prospectively increases the risk of incident cardiovascular disease (CVD) independent of other risk factors in otherwise healthy individuals. Between 10% and 20% of patients develop PTSD related to the traumatic experience of myocardial infarction (MI). We investigated the hypothesis that PTSD symptoms caused by MI predict adverse cardiovascular outcome. Methods We studied 297 patients (61 ± 10 years, 83% men) who self-rated PTSD symptoms attributable to a previous index MI. Non-fatal CVD-related hospital readmissions (i.e. recurrent MI, elective and non-elective intracoronary stenting, bypass surgery, pacemaker implantation, cardiac arrhythmia, cerebrovascular event) were assessed at follow-up. Cox proportional hazard models controlled for demographic factors, coronary heart disease severity, major CVD risk factors, cardiac medication, and mental health treatment. Results Forty-three patients (14.5%) experienced an adverse event during a mean follow-up of 2.8 years (range 1.3–3.8). A 10 point higher level in the PTSD symptom score (mean 8.8 ± 9.0, range 0–47) revealed a hazard ratio (HR) of 1.42 (95% CI 1.07–1.88) for a CVD-related hospital readmission in the fully adjusted model. A similarly increased risk (HR 1.45, 95% CI 1.07–1.97) emerged for patients with a major or unscheduled CVD-related readmission (i.e. when excluding patients with elective stenting). Conclusions Elevated levels of PTSD symptoms caused by MI may adversely impact non-fatal cardiovascular outcome in post-MI patients independent of other important prognostic factors. The possible importance of PTSD symptoms as a novel prognostic psychosocial risk factor in post-MI patients warrants further study.

A 13-year analysis from Switzerland of non-fatal sledging (sledding or tobogganing) injuries

INTRODUCTION: Winter sports have evolved from an upper class activity to a mass industry. Especially sledging regained popularity at the start of this century, with more and more winter sports resorts offering sledge runs. This study investigated the rates of sledging injuries over the last 13 years and analysed injury patterns specific for certain age groups, enabling us to make suggestions for preventive measures. METHODS: We present a retrospective analysis of prospectively collected data. From 1996/1997 to 2008/2009, all patients involved in sledging injuries were recorded upon admission to a Level III trauma centre. Injuries were classified into body regions according to the Abbreviated Injury Scale (AIS). The Injury Severity Score (ISS) was calculated. Patients were stratified into 7 age groups. Associations between age and injured body region were tested using the chi-squared test. The slope of the linear regression with 95% confidence intervals was calculated for the proportion of patients with different injured body regions and winter season. RESULTS: 4956 winter sports patients were recorded. 263 patients (5%) sustained sledging injuries. Sledging injury patients had a median age of 22 years (interquartile range [IQR] 14-38 years) and a median ISS of 4 (IQR 1-4). 136 (51.7%) were male. Injuries (AIS≥2) were most frequent to the lower extremities (n=91, 51.7% of all AIS≥2 injuries), followed by the upper extremities (n=48, 27.3%), the head (n=17, 9.7%), the spine (n=7, 4.0%). AIS≥2 injuries to different body regions varied from season to season, with no significant trends (p>0.19). However, the number of patients admitted with AIS≥2 injuries increased significantly over the seasons analysed (p=0.031), as did the number of patients with any kind of sledging injury (p=0.004). Mild head injuries were most frequent in the youngest age group (1-10 years old). Injuries to the lower extremities were more often seen in the age groups from 21 to 60 years (p<0.001). CONCLUSION: Mild head trauma was mainly found in very young sledgers, and injuries to the lower extremities were more frequent in adults. In accordance with the current literature, we suggest that sledging should be performed in designated, obstacle-free areas that are specially prepared, and that children should always be supervised by adults. The effect of routine use of helmets and other protective devices needs further evaluation, but it seems evident that these should be obligatory on official runs.

Long-term safety of intramuscular gene transfer of non-viral FGF1 for peripheral artery disease

Peripheral artery disease is a progressive disease. Primary ischemic leg symptoms are muscle fatigue, discomfort or pain during ambulation, known as intermittent claudication. The most severe manifestation of peripheral artery disease is critical limb ischemia (CLI). The long-term safety of gene therapy in peripheral artery disease remains unclear. This four center peripheral artery disease registry was designed to evaluate the long-term safety of the intramuscular non-viral fibroblast growth factor-1 (NV1FGF), a plasmid-based angiogenic gene for local expression of fibroblast growth factor-1 versus placebo in patients with peripheral artery disease who had been included in five different phase I and II trials. Here we report a 3-year follow-up in patients suffering from CLI or intermittent claudication. There were 93 evaluable patients, 72 of them in Fontaine stage IV (47 NV1FGF versus 25 placebo) and 21 patients in Fontaine stage IIb peripheral artery disease (15 NV1FGF versus 6 placebo). Safety parameters included rates of non-fatal myocardial infarction (MI), stroke, death, cancer, retinopathy and renal dysfunction. At 3 years, in 93 patients included this registry, there was no increase in retinopathy or renal dysfunction associated with delivery of this angiogenic factor. There was also no difference in the number of strokes, MI or deaths, respectively, for NV1FGF versus placebo. In the CLI group, new cancer occurred in two patients in the NV1FGF group. Conclusions that can be drawn from this relatively small patient group are limited because of the number of patients followed and can only be restricted to safety. Yet, data presented may be valuable concerning rates in cancer, retinopathy, MI or strokes following angiogenesis gene therapy in the absence of any long-term data in angiogenesis gene therapy. It may take several years until data from larger patient populations will become available.

Temporary scaffolding of coronary arteries with bioabsorbable magnesium stents: a prospective, non-randomised multicentre trial

BACKGROUND: Coronary stents improve immediate and late results of balloon angioplasty by tacking up dissections and preventing wall recoil. These goals are achieved within weeks after angioplasty, but with current technology stents permanently remain in the artery, with many limitations including the need for long-term antiplatelet treatment to avoid thrombosis. We report a prospective multicentre clinical trial of coronary implantations of absorbable magnesium stents. METHODS: We enrolled 63 patients (44 men; mean age 61.3 [SD 9.5 years]) in eight centres with single de novo lesions in a native coronary artery in a multicentre, non-randomised prospective study. Follow-up included coronary angiography and intravascular ultrasound at 4 months and clinical assessment at 6 months and 12 months. The primary endpoint was cardiac death, non-fatal myocardial infarction, or clinically driven target lesion revascularisation at 4 months FINDINGS: 71 stents, 10-15 mm in length and 3.0-3.5 mm in diameter, were successfully implanted after pre-dilatation in 63 patients. Diameter stenosis was reduced from 61.5 (SD 13.1%) to 12.6 (5.6%) with an acute gain of 1.41 mm (0.46 mm) and in-stent late loss of 1.08 mm (0.49 mm). The ischaemia-driven target lesion revascularisation rate was 23.8% after 4 months, and the overall target lesion revascularisation rate was 45% after 1 year. No myocardial infarction, subacute or late thrombosis, or death occurred. Angiography at 4 months showed an increased diameter stenosis of 48.4 (17.0%). After serial intravascular ultrasound examinations, only small remnants of the original struts were visible, well embedded into the intima. Neointimal growth and negative remodelling were the main operating mechanisms of restenosis. INTERPRETATION: This study shows that biodegradable magnesium stents can achieve an immediate angiographic result similar to the result of other metal stents and can be safely degraded after 4 months. Modifications of stent characteristics with prolonged degradation and drug elution are currently in development.

Prognosis of Atrial Fibrillation in Patients with Symptomatic Peripheral Arterial Disease: Data from the REduction of Atherothrombosis for Continued Health (REACH) Registry

BACKGROUND: Atrial fibrillation (AF) is a significant risk factor for cardiovascular (CV) mortality. This study aims to evaluate the prognostic implication of AF in patients with peripheral arterial disease (PAD). METHODS: The International Reduction of Atherothrombosis for Continued Health (REACH) Registry included 23,542 outpatients in Europe with established coronary artery disease, cerebrovascular disease (CVD), PAD and/or >/=3 risk factors. Of these, 3753 patients had symptomatic PAD. CV risk factors were determined at baseline. Study end point was a combination of cardiac death, non-fatal myocardial infarction (MI) and stroke (CV events) during 2 years of follow-up. Cox regression analysis adjusted for age, gender and other risk factors (i.e., congestive heart failure, coronary artery re-vascularisation, coronary artery bypass grafting (CABG), MI, hypertension, stroke, current smoking and diabetes) was used. RESULTS: Of 3753 PAD patients, 392 (10%) were known to have AF. Patients with AF were older and had a higher prevalence of CVD, diabetes and hypertension. Long-term CV mortality occurred in 5.6% of patients with AF and in 1.6% of those without AF (p<0.001). Multivariable analyses showed that AF was an independent predictor of late CV events (hazard ratio (HR): 1.5; 95% confidence interval (CI): 1.09-2.0). CONCLUSION: AF is common in European patients with symptomatic PAD and is independently associated with a worse 2-year CV outcome.

Influence of polyvascular disease on cardiovascular event rates. Insights from the REACH Registry

Cardiovascular event rates have been shown to increase substantially with the number of symptomatic disease locations. We sought to assess the risk profile, management and subsequent event rates of polyvascular disease patients. Consecutive outpatients were assessed for atherosclerotic risk factors and medications in the REACH Registry. A total of 19,117 symptomatic patients in Europe completed a 2-year follow-up: 77.2% with single arterial bed disease (coronary artery or cerebrovascular or peripheral arterial disease) and 22.8% with polyvascular disease (>/= 1 disease location). Polyvascular disease patients were older (68.5 +/- 9.4 vs 66.3 +/- 9.9 years, p < 0.0001), more often current or former smokers (64.9% vs 58.7%, p < 0.0001), and more often suffered from hypertension (59.5% vs 46.6%, p < 0.0001) and diabetes (34.5% vs 25.9%, p < 0.0001) than single arterial bed disease patients. Despite more intense medical therapy, risk factors (smoking, hypertension, low fasting glucose, and low fasting total cholesterol) were less often controlled in polyvascular disease patients. This was associated with substantially more events over 2 years compared with single arterial bed disease patients (cMACCE [cardiovascular death/non-fatal stroke/non-fatal MI] odds ratio, 1.63 [95% CI, 1.45-1.83], p < 0.0001). In conclusion, polyvascular disease patients have more cardiovascular risk factors, and the prognosis for these patients is significantly worse than for patients with single arterial bed disease. This suggests a need to improve detection and consequent medical treatment of polyvascular disease.

Distress related to myocardial infarction and cardiovascular outcome: a retrospective observational study

Background During acute coronary syndromes patients perceive intense distress. We hypothesized that retrospective ratings of patients' MI-related fear of dying, helplessness, or pain, all assessed within the first year post-MI, are associated with poor cardiovascular outcome. Methods We studied 304 patients (61 ± 11 years, 85% men) who after a median of 52 days (range 12-365 days) after index MI retrospectively rated the level of distress in the form of fear of dying, helplessness, or pain they had perceived at the time of MI on a numeric scale ranging from 0 ("no distress") to 10 ("extreme distress"). Non-fatal hospital readmissions due to cardiovascular disease (CVD) related events (i.e., recurrent MI, elective and non-elective stent implantation, bypass surgery, pacemaker implantation, cerebrovascular incidents) were assessed at follow-up. The relative CVD event risk was computed for a (clinically meaningful) 2-point increase of distress using Cox proportional hazard models. Results During a median follow-up of 32 months (range 16-45), 45 patients (14.8%) experienced a CVD-related event requiring hospital readmission. Greater fear of dying (HR 1.21, 95% CI 1.03-1.43), helplessness (HR 1.22, 95% CI 1.04-1.44), or pain (HR 1.27, 95% CI 1.02-1.58) were significantly associated with an increased CVD risk without adjustment for covariates. A similarly increased relative risk emerged in patients with an unscheduled CVD-related hospital readmission, i.e., when excluding patients with elective stenting (fear of dying: HR 1.26, 95% CI 1.05-1.51; helplessness: 1.26, 95% CI 1.05-1.52; pain: HR 1.30, 95% CI 1.01-1.66). In the fully-adjusted models controlling for age, the number of diseased coronary vessels, hypertension, and smoking, HRs were 1.24 (95% CI 1.04-1.46) for fear of dying, 1.26 (95% CI 1.06-1.50) for helplessness, and 1.26 (95% CI 1.01-1.57) for pain. Conclusions Retrospectively perceived MI-related distress in the form of fear of dying, helplessness, or pain was associated with non-fatal cardiovascular outcome independent of other important prognostic factors.

782 consecutive construction work accidents: who is at risk? A 10-year analysis from a Swiss university hospital trauma unit

BACKGROUND: Mortality and morbidity are particularly high in the building industry. The annual rate of non-fatal occupational accidents in Switzerland is 1,133 per 100,000 inhabitants. METHODS: Retrospective analysis of the electronic database of a university emergency centre. Between 2001 and 2011, 782 occupational accidents to construction workers were recorded and analysed using specific demographic and medical keywords. RESULTS: Most patients were aged 30-39 (30.4%). 66.4% of the injured workers were foreigners. This is almost twice as high as the overall proportion of foreigners in Switzerland or in the Swiss labour market. 16% of the Swiss construction workers and 8% of the foreign construction workers suffered a severe injury with ISS >15. There was a trend for workers aged 60 and above to suffer an accident with a high ISS (p = 0.089). CONCLUSIONS: As in other European countries, most patients were in their thirties. Older construction workers suffered fewer injuries, although these tended to be more severe. The injuries were evenly distributed through the working days of the week. A special effort should be made that current health and safety measures are understood and applied by foreign and older construction workers.

[Hypertension in the elderly]

Many aspects of hypertension diagnosis and treatment are similar in young and old patients. However, some differences exist. Due to the increasing vascular stiffness most elderly patients have isolated systolic hypertension and its prevalence in the population is high. Blood pressure should be measured in the sitting position and also with the patient standing to exclude orthostatic hypotension, a frequent problem in elderly patients. Pseudohypertension, a source of inadequate measurements in elderly patients, should be recognized. In comparison to other health problems there is good scientific evidence for antihypertensive treatment in elderly patients. As treatment does not only improve survival, but also reduces cardiovascular events such as non-fatal stroke or myocardial infarction, antihypertensive therapy is an important measure to prevent functional decline and disability.

Registry for the Evaluation of the Prognostik value of a novel integrated imaging approach combining Single Photon Emission Computed Tomography with coronary calcification imaging (REPROSPECT)

AIMS: Although an added diagnostic and prognostic value of the global coronary artery calcification (CAC) score as an adjunct to single-photon emission computed tomography (SPECT)-myocardial perfusion image (MPI) has been repeatedly documented, none of the previous studies took advantage of the anatomic information provided by the unenhanced cardiac CT. Therefore, no co-registration has so far been used to match a myocardial perfusion defect with calcifications in the subtending coronary artery. To evaluate the prognostic value of integrating SPECT-MPI with CAC images were obtained from non-enhanced cardiac computed tomography (CT) for attenuation correction to predict major adverse cardiac events (MACE). METHODS AND RESULTS: Follow-up was obtained in 462 patients undergoing a 1-day stress/rest (99m)Tc-teterofosmin SPECT and non-enhanced cardiac CT for attenuation correction. Survival free of MACE was determined using the Kaplan-Meier method. After integrating MPI and CT findings, patients were divided into three groups (i) MPI defect matched by calcification (CAC ≥ 1) in the subtending coronary artery (ii) unmatched MPI and CT finding (iii) normal finding by MPI and CT. At a mean follow-up of 34.5 ± 13 months, a MACE was observed in 80 patients (33 death, 6 non-fatal myocardial infarction, 9 hospitalizations due to unstable angina, and 32 revascularizations). Survival analysis revealed the most unfavourable outcome (P < 0.001 log-rank test) for patients with a matched finding. CONCLUSION: In the present study, a novel approach using a combined integration of cardiac SPECT-CAC imaging allows for refined risk stratification, as a matched defect emerged as an independent predictor of MACE.

Effects of anti-ischaemic drug therapy in silent myocardial ischaemia type I: the Swiss Interventional Study on Silent Ischaemia type I (SWISSI I): a randomized, controlled pilot study

AIMS: To determine the effect of anti-ischaemic drug therapy on long-term outcomes of asymptomatic patients without coronary artery disease (CAD) history but silent exercise ST-depression. METHODS AND RESULTS: In a randomized multicentre trial, 263 of 522 asymptomatic subjects without CAD but at least one CAD risk factor in whom silent ischaemia by exercise ECG was confirmed by stress imaging were asked to participate. The 54 (21%) consenting patients were randomized to anti-anginal drug therapy in addition to risk factor control (MED, n = 26) or risk factor control-only (RFC, n = 28). They were followed yearly for 11.2 +/- 2.2 years. During 483 patient-years, cardiac death, non-fatal myocardial infarction, or acute coronary syndrome requiring hospitalization or revascularization occurred in 3 (12%) of MED vs. 17 (61%) of RFC patients (P < 0.001). In addition, MED patients had consistently lower rates of exercise-induced ischaemia during follow-up, and left ventricular ejection fraction remained unchanged (-0.7%, P = 0.597) in contrast to RFC patients in whom it decreased over time (-6.0%, P = 0.006). CONCLUSION: Anti-ischaemic drug therapy and aspirin seem to reduce cardiac events in subjects with asymptomatic ischaemia type I. In such patients, exercise-induced ST-segment depression should be verified by stress imaging; if silent ischaemia is documented, anti-ischaemic drug therapy and aspirin should be considered.

Fixed low-dose ultrasound-assisted catheter-directed thrombolysis for intermediate- and high-risk pulmonary embolism

AIMS No standardized local thrombolysis regimen exists for the treatment of pulmonary embolism (PE). We retrospectively investigated efficacy and safety of fixed low-dose ultrasound-assisted catheter-directed thrombolysis (USAT) for intermediate- and high-risk PE. METHODS AND RESULTS Fifty-two patients (65 ± 14 years) of whom 14 had high-risk PE (troponin positive in all) and 38 intermediate-risk PE (troponin positive in 91%) were treated with intravenous unfractionated heparin and USAT using 10 mg of recombinant tissue plasminogen activator per device over the course of 15 h. Bilateral USAT was performed in 83% of patients. During 3-month follow-up, two [3.8%; 95% confidence interval (CI) 0.5-13%] patients died (one from cardiogenic shock and one from recurrent PE). Major non-fatal bleeding occurred in two (3.8%; 95% CI, 0.5-13%) patients: one intrathoracic bleeding after cardiopulmonary resuscitation requiring transfusion, one intrapulmonary bleeding requiring lobectomy. Mean pulmonary artery pressure decreased from 37 ± 9 mmHg at baseline to 25 ± 8 mmHg at 15 h (P < 0.001) and cardiac index increased from 2.0 ± 0.7 to 2.7 ± 0.9 L/min/m(2) (P < 0.001). Echocardiographic right-to-left ventricular end-diastolic dimension ratio decreased from 1.42 ± 0.21 at baseline to 1.06 ± 0.23 at 24 h (n = 21; P < 0.001). The greatest haemodynamic benefit from USAT was found in patients with high-risk PE and in those with symptom duration < 14 days. CONCLUSION A standardized catheter intervention approach using fixed low-dose USAT for the treatment of intermediate- and high-risk PE was associated with rapid improvement in haemodynamic parameters and low rates of bleeding complications and mortality.

Initiation of rivaroxaban in patients with nonvalvular atrial fibrillation at the primary care level:: The Swiss Therapy in Atrial Fibrillation for the Regulation of Coagulation (STAR) Study.

BACKGROUND Rivaroxaban has become an alternative to vitamin-K antagonists (VKA) for stroke prevention in non-valvular atrial fibrillation (AF) patients due to its favourable risk-benefit profile in the restrictive setting of a large randomized trial. However in the primary care setting, physician's motivation to begin with rivaroxaban, treatment satisfaction and the clinical event rate after the initiation of rivaroxaban are not known. METHODS Prospective data collection by 115 primary care physicians in Switzerland on consecutive nonvalvular AF patients with newly established rivaroxaban anticoagulation with 3-month follow-up. RESULTS We enrolled 537 patients (73±11years, 57% men) with mean CHADS2 and HAS-BLED-scores of 2.2±1.3 and 2.4±1.1, respectively: 301(56%) were switched from VKA to rivaroxaban (STR-group) and 236(44%) were VKA-naïve (VN-group). Absence of routine coagulation monitoring (68%) and fixed-dose once-daily treatment (58%) were the most frequent criteria for physicians to initiate rivaroxaban. In the STR-group, patient's satisfaction increased from 3.6±1.4 under VKA to 5.5±0.8 points (P<0.001), and overall physician satisfaction from 3.9±1.3 to 5.4±0.9 points (P<0.001) at 3months of rivaroxaban therapy (score from 1 to 6 with higher scores indicating greater satisfaction). In the VN-group, both patient's (5.4±0.9) and physician's satisfaction (5.5±0.7) at follow-up were comparable to the STR-group. During follow-up, 1(0.19%; 95%CI, 0.01-1.03%) ischemic stroke, 2(0.37%; 95%CI, 0.05-1.34%) major non-fatal bleeding and 11(2.05%; 95%CI, 1.03-3.64%) minor bleeding complications occurred. Rivaroxaban was stopped in 30(5.6%) patients, with side effects being the most frequent reason. CONCLUSION Initiation of rivaroxaban for patients with nonvalvular AF by primary care physicians was associated with a low clinical event rate and with high overall patient's and physician's satisfaction.

Long-term ticagrelor monotherapy versus standard dual antiplatelet therapy followed by aspirin monotherapy in patients undergoing biolimus-eluting stent implantation: rationale and design of the GLOBAL LEADERS trial

AIMS The GLOBAL LEADERS trial is a superiority study in patients undergoing percutaneous coronary intervention, with a uniform use of Biolimus A9-eluting stents (BES) and bivalirudin. GLOBAL LEADERS was designed to assess whether a 24-month antithrombotic regimen with ticagrelor and one month of acetylsalicylic acid (ASA), compared to conventional dual antiplatelet therapy (DAPT), improves outcomes. METHODS AND RESULTS Patients (n >16,000) are randomised (1:1 ratio) to ticagrelor 90 mg twice daily for 24 months plus ASA ≤100 mg for one month versus DAPT with either ticagrelor (acute coronary syndrome) or clopidogrel (stable coronary artery disease) for 12 months plus ASA ≤100 mg for 24 months. The primary outcome is a composite of all-cause mortality or non-fatal, new Q-wave myocardial infarction at 24 months. The key safety endpoint is investigator-reported class 3 or 5 bleeding according to the Bleeding Academic Research Consortium (BARC) definitions. Sensitivity analysis will be carried out to explore potential differences in outcome across geographic regions and according to specific angiographic and clinical risk estimates. CONCLUSIONS The GLOBAL LEADERS trial aims to assess the role of ticagrelor as a single antiplatelet agent after a short course of DAPT for the long-term prevention of cardiac adverse events, across a wide spectrum of patients, following BES implantation.