Abstract
Aims
Although highly heritable, the genetic etiology of calcific aortic stenosis (AS) remains incompletely understood. The aim of this study was to discover novel genetic contributors to AS ...and to integrate functional, expression, and cross-phenotype data to identify mechanisms of AS.
Methods and results
A genome-wide meta-analysis of 11.6 million variants in 10 cohorts involving 653 867 European ancestry participants (13 765 cases) was performed. Seventeen loci were associated with AS at P ≤ 5 × 10−8, of which 15 replicated in an independent cohort of 90 828 participants (7111 cases), including CELSR2–SORT1, NLRP6, and SMC2. A genetic risk score comprised of the index variants was associated with AS odds ratio (OR) per standard deviation, 1.31; 95% confidence interval (CI), 1.26–1.35; P = 2.7 × 10−51 and aortic valve calcium (OR per standard deviation, 1.22; 95% CI, 1.08–1.37; P = 1.4 × 10−3), after adjustment for known risk factors. A phenome-wide association study indicated multiple associations with coronary artery disease, apolipoprotein B, and triglycerides. Mendelian randomization supported a causal role for apolipoprotein B-containing lipoprotein particles in AS (OR per g/L of apolipoprotein B, 3.85; 95% CI, 2.90–5.12; P = 2.1 × 10−20) and replicated previous findings of causality for lipoprotein(a) (OR per natural logarithm, 1.20; 95% CI, 1.17–1.23; P = 4.8 × 10−73) and body mass index (OR per kg/m2, 1.07; 95% CI, 1.05–1.9; P = 1.9 × 10−12). Colocalization analyses using the GTEx database identified a role for differential expression of the genes LPA, SORT1, ACTR2, NOTCH4, IL6R, and FADS.
Conclusion
Dyslipidemia, inflammation, calcification, and adiposity play important roles in the etiology of AS, implicating novel treatments and prevention strategies.
Structured Graphical Abstract
Structured Graphical Abstract
Genetic etiology of aortic stenosis. This study meta-analyzed 13 765 AS cases vs. 640 102 controls and confirmed 15 genetic loci associated with AS. Downstream analyses implicated additional candidate genes involved in dyslipidemia, inflammation, calcification, and adiposity. The Manhattan plot shows variants with P ≥ 1 × 10−25, for improved visualization. Genetic loci in grey were previously identified, and those in gold are new discoveries. Abbreviations: AS, aortic stenosis; GWAS, genome-wide association study; LDL, low-density lipoprotein.
Pulmonary embolism is a serious disease and common among hospitalized patients. The incidence of pulmonary embolism in Iceland is largely unknown. The purpose of this study was to evaluate the ...incidence, clinical presentation, risk factors and outcome among patients diagnosed with pulmonary embolism at Landspítali, The National University Hospital of Iceland.
A retrospective analysis of medical records of patients diagnosed with the ICD-10 diagnosis I26 (Pulmonary embolism) between 2005-2007 was carried out. Data were retrieved on age, clinical manifestations, treatment, risk factors, diagnostic procedures and outcome.
The total number of patients was 312 and the in-hospital incidence was 5 per 1.000. Thirty day mortality was 9.9% (95% CI 6.6-13.3). Dyspnea was the most common symptom (81%) and diagnosis was most often established by computed tomography of the pulmonary vasculature (88,8%). Anticoagulation was by far the most common management (96%) but thrombolysis, thrombectomy or use of inferior vena cava filters were very rare. The frequency of atrial fibrillation was significantly higher in patients with pulmonary hypertension by echocardiography than without, 32.4% and 9.7%, respectively (p= 0.026). Thirty day mortality was significantly higher in women than in men (13.2% versus 6.5%, p=0.049), and in patients with no classic symptoms of pulmonary embolism at diagnosis (36.4% versus 8.1%, p=0.012).
The hospital incidence of pulmonary embolism, 5/1000 patients, at Landspítali The National University Hospital of Iceland is higher than found in similar studies in many other countries. Mortality, while similar, has fallen markedly during the past 40 years.
To compare the utility and reliability of coronary angiography with multislice computed tomography (MSCT) and by cardiac catheterisation in assessing atherosclerotic lesions and stenosis.
Data were ...assessed from 44 subjects (25 men, 19 women) (mean age 63 years; range 34-80 years) referred to MSCT who also had undergone invasive coronary angiography within a time frame of one year. Coronary angiograms from both studies were assessed by segmental analysis and the atherosclerotic severity graded. The frequency of coronary calcification on MSCT was separately assessed in 150 subjects.
By retrospective evaluation, 29 segments were found to have significant stenosis (> or = 50%) on the invasive coronary angiogram. Of these 17 had a diameter over 2.0 mm and 14 (83%) thereof were correctly diagnosed by MSCT. On the other hand, MSCT assessed four stenosis to be significant that were not judged so on the invasive angiogram. On MSCT, the frequency of coronary calcifications increased with age and in those 60 years and older it was 96% in males and 71% in females (p=0.025).
Good agreement was found between MSCT and invasive coronary angiography in assessing significant stenosis in vessel segments over 2.0 mm. In older subjects coronary calcification on MSCT is frequent and diminishes its accuracy. MSCT seems most useful in relatively young subjects in whom the coronary arteries need to be evaluated to avoid unnecessary cardiac catheterisation.
Mitral valve replacement (MVR) is the second most common valvular replacement procedure after aortic valve replacement (AVR). Studies on the outcome of MVR in Iceland have been missing. We therefore ...studied short and long-term results following MVR in Iceland,
A retrospective nationwide study on 64 patients (mean age 59 years, 63% males) that underwent 66 MVR procedures in Iceland between 1990-2010. Clinical data was retrieved from patient charts and overall survival estimated. The mean follow-up was 7.4 years.
Mitral regurgitation or stenosis was the indication for MVR in 71% and 27% of cases, respectively. Nine patients had endocarditis and 8 a recent myocardial infarction. The mean logEuroSCORE was 14.9% (range 1.5-88.4), 83% of the patients were in NYHA class III/IV preoperatively and 24% had previously undergone cardiac surgery. A biological valve was implanted in six cases and a mechanical valve used in 60 cases. Concomitant CABG was performed in 41% of patients and AVR in 20%. Perioperative myocardial infarction (26%), acute respiratory failure (17%), reoperation for bleeding (15%) and acute renal failure requiring dialysis (9%) were the most common major complications. Three patients required extracorporeal membrane oxygenation (ECMO) and six patients an intra-aortic balloon pump (IABP) postoperatively. Minor complications were noted in 61% of cases. Six patients died within 30 days (9%) and five year survival was 69%.
The frequency of complication following MVR was high and represents the severity of the underlying heart disease. The operative mortality in the current study was in the lower range compared to other studies.
Information on surgical outcome of aortic valve replacement (AVR) has not been available in Iceland. We therefore studied the indications, short-term complications and operative mortality in ...Icelandic patients that underwent AVR with aortic stenosis.
This was a retrospective study including all patients that underwent AVR for aortic stenosis at Landspitali between 2002 and 2006, a total of 156 patients (average age 71.7 years, 64.7% males). Short term complications and operative mortality (≤ 30 days) were registered and risk factors analysed with multivariate analysis.
The most common symptoms before AVR were dyspnea (86.9%) and angina pectoris (52.6%). Preop. max aortic valve pressure gradient was on average 74 mmHg, the left ventricular ejection fraction 57.2% and EuroSCORE (st) 6.9%. The average operating time was 282 min and concomitant CABG was performed in 55% of the patients and mitral valve surgery in nine. A bioprothesis was implanted in 127 of the patients (81.4%), of which 102 were stentless valves, and a mechanical valve in 29 (18.6%) cases. The mean prosthesis size was 25.6 mm (range 21-29). Atrial fibrillation (78.0%) and acute renal injury (36.0%) were the most common complications and 20 patients (13.0%) developed multiple-organ failure. Twenty-six patients (17.0%) needed reoperation due to bleeding. Median hospital stay was 13 days and operative mortality was 6.4%.
The rate of short term complications following AVR was relatively high, including reoperations for bleeding and atrial fibrillation. Operative mortality is twice that of CABG, which is in line with other studies.
Apical ballooning syndrome, case series Gudnadóttir, Gudný Stella; Sigurjónsson, Hannes; Gudjónsson, Thorbjörn ...
Laeknabladid
94, Številka:
11
Journal Article
Recenzirano
Apical ballooning syndrome is a cardiac syndrome typically characterized by transient focal dyskinesia or akinesia of the mid and apical regions of the left ventricle and hyperkinesia of the basal ...region. The symptoms and signs of the patient mimic myocardial infarction, with chest pain, electrocardiographic changes and elevation of cardiac enzymes but without significant coronary artery disease. The syndrome is frequently preceded by physical or emotional stress. We describe three cases of apical ballooning syndrome diagnosed during 10 days in December 2007 at Landspítali University Hospital Reykjavík.
To investigate long-term complications and survival following aortic valve replacement (AVR) in patients with aortic stenosis (AS) in Iceland.
Included were 156 patients (average age 71.7 yrs, 64.7% ...males) that underwent AVR for AS at Landspitali between 2002 and 2006. A mechanical prosthesis was used in 29 patients (18.6%) and a bioprosthesis in 127. Long-term complications and operation-related admissions were registered from hospital and outpatient records until April 1, 2010. Overall survival was estimated and compared with the Icelandic population of the same age and gender.
The mean preop. EuroSCORE(st) was 6.9%, the max. transvalvular pressure gradient 74.1 mmHg and the left ventricular ejection fraction (LVEF) (57.2%). At six months following AVR the maximal pressure gradient was 19.8 mmHg (range; 2.5-38). Echocardiography results were not available for 23.6% of the patients 6 months postoperatively. In the follow-up period one in four patients was admitted due to valve-related problems. Re-admission rate was 6.0/100 patient-years (pt-y); most commonly due to cardiac failure (1.7/100 pt-y), emboli (1.6/100 pt-y), hemorrhage (1.6/100 pt-y), endocarditis (0.7/100 pt-y) and myocardial infarction (0.4/100 pt-y). Survival at 1 and 5 year was 89.7% and 78.2%, respectively, making survival comparable to the estimated survival of Icelanders of the same age and gender.
The rate of long-term complications following AVR in Iceland is in line with other studies. The same applies to long-term survival, which was similar to that of the Icelandic population of the same age and gender. Key words: Aortic valve replacement, aortic stenosis, heart surgery, results, long-term complication, survival.
Constricitve pericarditis is an uncommon condition, often of unknown etiology but can be caused by infections, such as tuberculosis, inflammation of the pericardium, radiation therapy or asbestos ...exposure. Constrictive pericarditis is characterized by fibrosis and often severe calcifications of the pericardial sac which eventually restricts normal diastolic filling of the heart. This consequently leads to a combination of left and right heart failure, often with prominent jugular venous distentsion, liver enlargement, peripheral edema and lethargy. Diagnosis can be difficult and is often delayed. Surgery, involving partial removal of the pericardial sac, usually leads to relief of symptoms. Here we report a case from Landspitali together with a review of the literature.
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