Risk of ischaemic heart disease and cardiomyopathy in patients with haemochromatosis and in their first-degree relatives: a nationwide, population-based study.

BACKGROUND: Iron-loaded macrophages increase atherosclerosis formation. Genetic haemochromatosis (GH) is an autosomal recessive disease characterized by iron overload, for example in the myocardium, but the reticuloendothelial system is depleted of iron. In contrast to the elevated risk of cardiomyopathy in GH, the risk of ischaemic heart disease (IHD) may therefore not be increased. Little is known of these risks among heterozygotes also being first-degree relatives (FDRs), thus sharing other factors for phenotypic expression of GH. OBJECTIVE: To assess the risks of IHD and cardiomyopathy among haemochromatosis patients and their FDRs. DESIGN: Population-based cohort study. SETTING AND SUBJECTS: A total of 3531 haemochromatosis patients and 11 794 FDRs were identified using nationwide, population-based health and census registers. Matched (1:10) population controls were randomly selected. Individuals with a record of IHD and cardiomyopathy during 1997-2005 were identified through linkage with the National Patient Register. Relative risks were estimated using Cox proportional hazard regression. RESULTS: Of the 3531 patients, 259 were diagnosed with IHD compared with 3077 of the 37 369 controls [hazard ratio (HR) = 1.17; 95% CI, 1.03-1.33]. Based on 30 patients versus 115 controls, the HR for cardiomyopathy was 3.21 (95% CI, 2.15-4.81). Of 11 794 FDRs of haemochromatosis patients, 582 were registered with IHD compared with 6197 among FDRs of controls (HR = 1.05; 95% CI, 0.97-1.15). Based on 28 FDRs of patients versus 291 FDRs of controls registered with cardiomyopathy, the HR for cardiomyopathy was 1.06 (95% CI, 0.72-1.56). CONCLUSIONS: In patients with haemochromatosis, the increased risk of cardiomyopathy is much more pronounced than that of IHD, which is barely elevated. FDRs of haemochromatosis patients are not at increased risk of cardiomyopathy or IHD.

Long-term effects of spinal cord stimulation on angina symptoms and quality of life in patients with refractory angina pectoris--results from the European Angina Registry Link Study (EARL).

OBJECTIVE: To assess the long-term effect of spinal cord stimulation (SCS) on angina symptoms and quality of life in patients with refractory angina pectoris defined as severe angina due to coronary artery disease resistant to conventional pharmacological therapy and/or revascularisation. METHODS: During 2003-2005, all patients with refractory angina referred for SCS treatment at 10 European centres were consecutively included in the European registry for refractory angina (European Angina Registry Link, EARL), a prospective, 3-year follow-up study. In the present study, the SCS-treated patients were followed-up regarding angina symptoms and quality of life assessed was with a generic (Short Form 36, SF-36) and a disease-specific (Seattle Angina Questionnaire, SAQ) quality of life questionnaire. RESULTS: In total, 235 patients were included in the study. After screening, 121 patients were implanted and followed up 12.1 months after implantation. The implanted patients reported fewer angina attacks (p<0.0001), reduced short-acting nitrate consumption (p<0.0001) and improved Canadian Cardiovascular Society class (p<0.0001). Furthermore, quality of life was significantly improved in all dimensions of the SF-36 and the SAQ. Seven (5.8%) of the implanted patients died within 1 year of follow up. CONCLUSIONS: SCS treatment is associated with symptom relief and improved quality of life in patients with refractory angina pectoris suffering from severe coronary artery disease.

Effects of low-dose warfarin and aspirin versus no treatment on stroke in a medium-risk patient population with atrial fibrillation.

OBJECTIVES: To assess the optimal stroke prevention treatment for patients with atrial fibrillation (AF) and a low-medium risk (< or =4%) of stroke. DESIGN: A total of 668 patients with persistent or permanent AF, without an indication for full dose and with adequate rate control on sotalol, were randomized to warfarin 1.25 mg + aspirin 75 mg daily (W/A, 334 patients) or no anticoagulation (C, 334 patients). The mean follow-up period was 33 months. The protocol intended to verify a 37% relative risk reduction provided a 4% stroke incidence in the C group. RESULTS: The stroke incidence was less in the W/A group, although the reduction was not statistically significant (W/A 9.6% versus C 12.3%). Four haemorrhagic strokes were identified, two in each group. Secondary end-points were transient ischaemic attacks (TIA) (W/A 3.3% versus C 4.5%), all cause mortality (W/A 9.3% versus C 10.8%), cardiovascular morbidity (W/A 17.7% versus C 22.2%) and the combination of stroke + TIA (W/A 11.7% versus C 16.5%). Bleedings were documented in 19 versus four patients (W/A 5.7% versus C 1.2%) (P = 0.003), although none fatal. Sinus rhythm (SR) was recorded occasionally in 68 patients (W/A 9.6% versus C 10.8%). The stroke incidence tended to be higher in those with SR than without, 16.2% versus 10.4%. CONCLUSIONS: Our results were inconclusive, but consistent with a small beneficial effect of W/A for reduction of stroke and major vascular events in AF patients at moderate risk. The low-dose regiment produced, however, a significantly increased risk of bleedings. Documented SR occasionally recorded may represent a subpopulation that warrants full dose warfarin.

Incidence and predictors of bleeding events after fibrinolytic therapy with fibrin-specific agents: a comparison of TNK-tPA and rt-PA.

BACKGROUND: Fibrinolytic therapy increases the risk of bleeding events. TNK-tPA (tenecteplase) is a variant of rt-PA with greater fibrin specificity and reduced plasma clearance that can be given as a single bolus. We compared the incidence and predictors of bleeding events after treatment with TNK-tPA and rt-PA. METHODS AND RESULTS: In the Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT)-2 trial, 16 949 patients with acute myocardial infarction were randomly assigned a single weight-adjusted bolus of TNK-tPA or a 90-min infusion of rt-PA. A total of 4.66% of patients in the TNK-tPA group experienced major non-cerebral bleeding, in comparison with 5.94% in the rt-PA group (P=0.0002). This lower rate was associated with a significant reduction in the need for blood transfusion (4.25% vs 5.49%, P=0.0003) and was consistent across subgroups. Independent risk factors for major bleeding were older age, female gender, lower body weight, enrolment in the U.S.A. and a diastolic blood pressure <70 mmHg. Females at high risk (age >75 years and body weight <67 kg) were less likely to have major bleeding when treated with TNK-tPA even after other risk factors were taken into account. A total of 0.93% of patients in the TNK-tPA and 0.94% of patients in the rt-PA group experienced an intracranial haemorrhage. Female patients >75 years of age who weighed <67 kg tended to have lower rates of intracranial haemorrhage when treated with TNK-tPA (3/264, 1.14% vs 8/265, 3.02%). CONCLUSIONS: The increased fibrin specificity and single bolus administration of TNK-tPA do not increase the risk of intracranial haemorrhage but are associated with less non-cerebral bleeding, especially amongst high-risk patients.

[Thrombosis of mechanical tricuspid valve. Thrombolysis should be considered as a first line approach]. / Trombotiserad mekanisk trikuspidalklaff. Trombolys bör övervägas i första hand.

This report describes a 60-year old man who three years earlier, due to tricuspid endocarditis, had undergone surgery entailing insuturation of a Carbomedic valve prosthesis. He was admitted via the emergency room with clinical signs of right heart failure, and he reported that he had not heard the valve sound for two to three weeks. Cineradiography revealed a dysfunction of the tricuspid valve prosthesis, with the bileaflet tilting disc closed in the opening position. Thrombolytic therapy was successful. We review the literature on obstructed mechanical prosthetic valves and on the use of thrombolysis.

Health-related quality of life in patients with adolescent idiopathic scoliosis: a matched follow-up at least 20 years after treatment with brace or surgery.

No results on long-term outcome in terms of health-related quality of life (HRQL) have previously been presented for patients treated for adolescent idiopathic scoliosis. A consecutive series of patients with adolescent idiopathic scoliosis, treated between 1968 and 1977 before the age of 21, either with distraction and fusion using Harrington rods [surgical treatment group (ST), n=156; 145 females and 11 males] or with a brace [brace treatment group (BT), n=127; 122 females and 5 males] were followed at least 20 years after completion of the treatment. Ninety-four percent of ST and 91% of BT patients filled in a questionnaire comprising the SF-36, Psychological General Well-Being Index (PGWB), Oswestry Disability Back Pain Questionnaire, parts of SRS/MODEM'S questionnaire and study-specific questions concerning the treatment, as a part of an unbiased personal follow-up examination including radiography and clinical examination. An age- and sex-matched control group of 100 persons was randomly selected and subjected to the same examinations. The results showed no differences in terms of sociodemographic data between the groups. Both ST and BT patients had a slightly, but significantly, reduced physical function using the SF-36 subscales, SF-36/Physical Component Summary (PCS) score as well as the Oswestry Disability Back Pain Questionnaire compared to the controls. Neither the mental subscales and the Mental Component Summary (MCS) score of SF-36 nor the PGWB index showed any significant difference between the groups. Forty-nine percent of ST, 34% of BT and 15% of controls admitted limitation of social activities due to their back [P<0.001 ST vs controls, P=0.0010 BT vs controls, and n.s. (P=0.024) ST vs BT], mostly due to difficulties with physical participation in activities or self-consciousness about appearance. Pain was a minor reason for limitation. No correlation was found between the outcome scores and curve size after treatment, curve type, total treatment time or age at completed treatment. Patients treated for adolescent idiopathic scoliosis were found to have approximately the same HRQL as the general population. A minority of the patients (4%) had a severely decreased psychological well-being, and a few (1.5%) were severely physically disabled due to the back.

The low-molecular-weight heparin dalteparin as adjuvant therapy in acute myocardial infarction: the ASSENT PLUS study.

Rapid reperfusion of an infarct-related artery reduces the extent of myocardial damage and improves survival in acute myocardial infarction (AMI). Currently, anticoagulant treatment with unfractionated heparin (UFH) is used as adjuvant therapy to fibrinolytic treatment. The low-molecular-weight heparin (LMWH) dalteparin is at least as effective as UFH in unstable coronary artery disease. The ASSENT PLUS trial was carried out to evaluate whether dalteparin is as effective as UFH as an adjunct to recombinant tissue-plasminogen activator (rt-PA) and aspirin in obtaining patency and Thrombolysis in Myocardial Infarction (TIMI)-3 flow in patients with AMI. The primary assessment of this phase II trial was TIMI flow, determined by coronary angiography. Patients with ST-elevation MI were randomized to receive aspirin and either rt-PA and UFH for 48 h, or rt-PA and dalteparin for 4 to 7 days. Evaluation was by TIMI flow after 4 to 7 days and clinical events (death, reinfarction, or revascularization) up to 30 days. There was a clear trend toward greater TIMI 3 flow with dalteparin compared with UFH. There was significantly less TIMI 0-1 flow or thrombus in the dalteparin group. Bleeding rates were similar. The occurrence of reinfarction was reduced during dalteparin treatment. These findings suggest that dalteparin could be substituted for UFH as an adjunct to rt-PA/aspirin in the management of patients with AMI.

Pulmonary function in adolescent idiopathic scoliosis: a 25 year follow up after surgery or start of brace treatment.

BACKGROUND: Pulmonary function in patients with adolescent idiopathic scoliosis many years after posterior spinal surgery or brace treatment has not been documented. METHODS: A consecutive group of patients treated by posterior fusion or a brace at least 20 years previously was investigated. 90% attended a clinical follow up. Lung volumes were determined before treatment in 251 patients, 1.4 years after surgery in 141 patients, and 25 years after surgery or start of brace treatment in 110 patients. Vital capacity (VC) was calculated as percentage predicted according to height and age and the results were corrected for loss of height due to scoliosis. Scoliosis angles were measured and smoking habits were recorded. An age and sex matched control group was also examined with the same questionnaire and pulmonary function tests. RESULTS: VC increased from 67% predicted immediately before surgery to 73% (p<0.001) after surgery and to 84% (p<0.001) at the present follow up, mean change 10.8% (95% CI 9.5 to 12.1). In the brace treated patients VC increased from 77% predicted before treatment to 89% (p<0.001) 25 years after start of treatment, mean change 12.3% (95% CI 10.5 to 14.1). The mean Cobb angle at the present follow up study was 40 degrees in both surgically and brace treated patients. The present results of lung volumes did not correlate with pretreatment or post-treatment Cobb angles or smoking habits. CONCLUSIONS: Patients treated by posterior fusion or a brace gradually increase their pulmonary function up to 25 years after treatment. Smoking and curve size are not risk factors for reduced pulmonary function.

Left ventricular systolic dysfunction in 75-year-old men and women; a population-based study.

AIMS: To determine the prevalence of left ventricular systolic dysfunction in 75-year-old men and women. METHODS AND RESULTS: In a population-based random sample of 75-year-old subjects (n=433; response rate 70.1%) the left ventricular systolic function was determined using two echocardiographic methods: (1) wall motion in nine left ventricular segments was visually scored and wall motion index was calculated as the mean value of the nine segments and (2) ejection fraction as measured by the disc summation method. Presence of heart failure was determined by a cardiologist's clinical evaluation. Wall motion index was achievable in 95% of the participants while ejection fraction was measurable in 65%. Normal values were obtained from a healthy subgroup (n=108) and left ventricular systolic dysfunction was defined as the 0.5th percentile of the wall motion index (i.e. <1.7). In participants in whom both ejection fraction and wall motion index were achievable, wall motion index <1.7 predicted ejection fraction <43% with a sensitivity and specificity of 84.0% and 99.6%, respectively. The prevalence of left ventricular systolic dysfunction was 6.8% (95% CI, 5.6--8.0%) and was greater in men than in women (10.2% vs 3.4%, P=0.006). Clinical evidence of heart failure was absent in 46% of the participants with left ventricular systolic dysfunction. CONCLUSIONS: Left ventricular systolic dysfunction is common among 75-year-olds with a prevalence of 6.8% in our estimate. The condition is more likely to affect men than women. In nearly half of 75-year-olds with left ventricular systolic dysfunction there is no clinical evidence of heart failure.

Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 double-blind randomised trial.

BACKGROUND: Bolus fibrinolytic therapy facilitates early efficient institution of reperfusion therapy. Tenecteplase is a genetically engineered variant of alteplase with slower plasma clearance, better fibrin specificity, and high resistance to plasminogen-activator inhibitor-1. We did a double-blind, randomised, controlled trial to assess the efficacy and safety of tenecteplase compared with alteplase. METHODS: In 1021 hospitals, we randomly assigned 16,949 patients with acute myocardial infarction of less than 6 h duration rapid infusion of alteplase (< or = 100 mg) or single-bolus injection of tenecteplase (30-50 mg according to bodyweight). All patients received aspirin and heparin (target activated partial thromboplastin time 50-75 s). The primary outcome was equivalence in all-cause mortality at 30 days. FINDINGS: Covariate-adjusted 30-day mortality rates were almost identical for the two groups--6.18% for tenecteplase and 6.15% for alteplase. The 95% one-sided upper boundaries of the absolute and relative differences in 30-day mortality were 0.61% and 10.00%, respectively, which met the prespecified criteria of equivalence (1% absolute or 14% relative difference in 30-day mortality, whichever difference proved smaller). Rates of intracranial haemorrhage were similar (0.93% for tenecteplase and 0.94% for alteplase), but fewer non-cerebral bleeding complications (26.43 vs 28.95%, p=0.0003) and less need for blood transfusion (4.25 vs 5.49%, p=0.0002) were seen with tenecteplase. The rate of death or non-fatal stroke at 30 days was 7.11% with tenecteplase and 7.04% with alteplase (relative risk 1.01 [95% CI 0.91-1.13]). INTERPRETATION: Tenecteplase and alteplase were equivalent for 30-day mortality. The ease of administration of tenecteplase may facilitate more rapid treatment in and out of hospital.

Effect of protriptyline, 10 mg daily, on chronic hypoxaemia in chronic obstructive pulmonary disease.

A daily dose of 20 mg of protriptyline can improve daytime arterial blood gas tensions in chronic obstructive pulmonary disease (COPD). Its usefulness is limited by anticholinergic side-effects. This study examined whether a daily dose of 10 mg of protriptyline improved daytime arterial oxygen tension (PaO2) and quality of life in patients with stable mild or moderate hypoxaemia caused by COPD. Twenty six patients were randomized to receive protriptyline or placebo in a double-blind parallel-group trial for 12 weeks, following a run-in period of 4 weeks, in order to assess the stability of hypoxaemia. Patients with a change in PaO2 of > 0.7 kPa during the run-in were excluded. Spirometry, quality of life and dyspnoea score were measured at randomization and after 12 weeks, whilst arterial blood gas tensions were also measured 2 and 6 weeks after randomization. No improvement in arterial blood gas tensions, spirometry values, dyspnoea score, or quality of life was found in either the protriptyline or the placebo group. The majority of patients receiving protriptyline experienced anticholinergic side-effects, which necessitated the withdrawal of the drug in one patient. We conclude that there was no evidence that a daily dose of 10 mg of protriptyline had a significant effect on daytime arterial oxygen tension in stable mild and moderate hypoxaemia caused by COPD. Despite the low dose, anticholinergic side-effects occurred in most patients.

Quality of life of patients treated by home mechanical ventilation due to restrictive ventilatory disorders.

The quality of life of patients with hypoventilation and home mechanical ventilation (HMV) has not been well described. Modern quality of life assessment techniques were therefore introduced in a cross-sectional study of patients treated with HMV. The aim was to study various aspects of the patient's quality of life and relate them to the underlying diseases, blood gases and the type of ventilatory connection. The study comprised 39 patients, most of them ventilated only during the night (n = 35). Nasal ventilation predominated (n = 29). Patients treated with HMV reported satisfactory levels of both psychosocial functioning and mental well-being that compared well with a general population group. Their quality of sleep was generally good. The quality of life measures were mainly influenced by the patients' underlying disease. Patients with scoliosis expressed in almost all instances the best quality of life. The quality of life of patients with ventilation by tracheostomy was reported to be at least as good as that of patients with nasal ventilation. The global quality of life estimation was mainly determined by the mental state of the patients and their sleep quality and only to a minor extent by physical handicaps. In conclusion, the patients treated with HMV reported good psychosocial functioning and mental well-being, in spite of severe physical limitations and dependence on regular nocturnal ventilation.

Long-term follow-up of patients with untreated scoliosis. A study of mortality, causes of death, and symptoms.

The mortality and causes of death in 115 patients (80 women), born 1902-1937, with untreated scoliosis were compared to the expected according to official Swedish statistics. Subgrouping for cause and onset of scoliosis was done. Fifty-five patients had died; 21 of respiratory failure and 17 of cardiovascular diseases. The mortality was significantly (P less than 0.001) increased. The increased risk was apparent at 40-50 years of age. The mortality was significantly increased in infantile (P less than 0.001) and juvenile (P less than 0.01) scoliosis but not in adolescent scoliosis. The mortality was also increased in post-polio scoliosis, scoliosis combined with rickets and scoliosis of unknown etiology indicating an increased mortality in idiopathic scoliosis. Among the surviving patients anti-hypertensive treatment was frequent (23 of 50).

Survival of patients with severe thoracic spine deformities receiving domiciliary oxygen therapy.

Scoliosis can lead to respiratory failure and premature death. Alveolar hypoventilation is a dominant cause and artificial ventilation at home (AVH) is probably the treatment of choice. It has been suggested that long-term domiciliary oxygen therapy (LTO) is of little value because of the worsening of hypercapnia. We analyzed survival and predictors of death among 80 patients with scoliosis and other severe thoracic spine deformities receiving LTO for chronic hypoxia. The survival rate was higher in patients under the age of 65 (p = 0.01) and in patients without concomitant pulmonary or airways disease. Likewise, the survival rate was higher in patients with a PaCO2 of greater than 7.4 kPa than in patients with a lesser degree of hypoventilation and hypercapnia (p less than 0.05). The risk of developing life-threatening hypercapnia during well-controlled LTO appeared to be small. In younger patients without complicating disease, long-term survival was achieved with LTO, but with time, an increasing proportion of the patients changed to AVH, with or without LTO.

Respiratory failure in scoliosis and other thoracic deformities. A survey of patients with home oxygen or ventilator therapy in Sweden.

Registers covering Swedish patients with home ventilator or long-term oxygen therapy were used to study respiratory failure caused by thoracic deformities. In all, 107 patients were studied. Postpolio scoliosis was found in 47 patients. The age of starting therapy varied between 28 and 80 years. Fourteen patients had thoracic deformities other than scoliosis. The mean scoliotic angle was 135 degrees among the patients with scoliosis, and the mean vital capacity was 26% (range, 13-54%) of predicted normal. The yearly demand for home ventilator or oxygen therapy is calculated to three per million inhabitants. No operated patients had respiratory failure, and no patients were found with idiopathic scoliosis and respiratory failure younger than 30 years of age, which may indicate a preventive effect of corrective surgery on the development of respiratory failure.

Exercise performance and beta-adrenergic blockade in patients with complete heart block treated with ventricular inhibited pacing.

The effect of beta-adrenergic blockade (propranolol) on exercise performance was studied in 15 patients (12 men and 3 women, mean age 70 years) with complete heart block treated with a ventricular-inhibited pacemaker (VVI). In a double-blind procedure, the patients were randomly given either 0.1 mg/kg of propranolol or saline solution i.v. before a first exercise test and vice versa before a second test. The interval between the tests was 24 hours. Nine patients were in sinus rhythm, 4 patients had atrial flutter, and 2 others had atrial fibrillation. The exercise capacity was on an average 11% lower with propranolol than with placebo (p less than 0.001). The most marked reductions (20 and 33%) were found in the two patients with atrial fibrillation. The atrial rate in patients with sinus rhythm was significantly lower with propranolol than placebo both at rest (68 vs. 83 beats/min, p less than 0.001) and at maximal work load (91 vs. 141 beats/min, p less than 0.001). The present findings show that beta blockade has negative effects on exercise capacity in patients with complete heart block treated with VVI pacemakers. This finding should be considered in the selection of drug treatment in patients with fixed rate pacing and concomitant hypertension and/or ischemic heart disease.

Lung function in adult idiopathic scoliosis: a 20 year follow up.

Severe idiopathic scoliosis may lead to respiratory failure, which can be treated by assisted ventilation. Twenty four patients with surgically untreated idiopathic scoliosis who had been examined in 1968 were re-examined in 1988 to assess changes in lung function and risk factors for respiratory failure. The patients were aged 15-67 years in 1968 and had a scoliotic angle of 10-190 degrees and a vital capacity of 1.0-6.0 litres. Spirometric values and scoliotic angles were determined in 1968 and 1988, and arterial blood gas tensions in 1988. The decline in spirometric values over the 20 years was of the same magnitude as the predicted decline due to aging. Arterial blood gas tensions in 1988 were strongly correlated with the scoliotic angles and spirometric indices recorded in 1968. Hypoxaemia and hypercapnia was seen in four patients in 1988 (then aged 43-67 years) and these were the four patients who had a vital capacity below 43% predicted in 1968. The remaining 20 patients had blood gas values within normal limits. Two further patients had died from respiratory failure before 1988, so a total of six patients had developed respiratory failure. In a multiple logistic analysis vital capacity expressed as % predicted in 1968 was the strongest predictor of the development of respiratory failure, followed by the scoliotic angle. Respiratory failure occurred only in patients who had a vital capacity below 45% predicted in 1968 and an angle greater than 110 degrees. Thus respiratory failure develops in adults with scoliosis with a large angle and a low vital capacity when normal aging reduces the ventilatory capacity further. Such individuals merit close follow up.