Outbreak of Puumala Virus Infection, Sweden

An unexpected and large outbreak of Puumala virus infection in Sweden resulted in 313 nephropathia epidemica patients/100,000 persons in Västerbotten County during 2007. An increase in the rodent population, milder weather, and less snow cover probably contributed to the outbreak

Endothelial dysfunction in patients with glucose abnormalities and coronary artery disease : Studies of pathogenesis and treatment

Background Type 2 diabetes is associated with endothelial dysfunction, which is characterised by the reduced bioavailability of nitric oxide (NO). This is a result of increased oxidative stress and inflammation and the synthesis of endothelium-dependent vasoconstricting factors such as endothelin-1 (ET-1) caused by hyperglycaemia, insulin resistance and dyslipidemia. The dysfunction of the vascular endothelium is regarded as an important factor for the increased risk of cardiovascular disease seen in patients with type 2 diabetes and it is thought to play a major role in the pathogenesis of both micro- and macrovascular complications in this patient category. This thesis aims to further explore the pathogenesis and treatment options of endothelial dysfunction in patients with glucose abnormalities. Studies I-II The importance of the lipid-independent (pleiotropic) effects of statins was studied in 43 patients with dysglycemia and coronary artery disease. Intensive lipid lowering with either 80 mg of simvastatin or a combination of 10 mg of simvastatin together with 10 mg of ezetimibe improved macrovascular endothelial function and microvascular function (n=36) and reduced inflammation. No difference between the two treatment strategies was found, indicating that the improvements were mainly due to lipid lowering and not to the pleiotropic effects of statins. Study III The effect of endothelin-A-receptor blockade on nutritive skin capillary circulation in patients with type 2 diabetes and microangiopathy was studied. Intra-arterial infusions of an endothelin-A-receptor antagonist improved nutritive skin capillary circulation in patients with type 2 diabetes (n=10) but not in healthy controls (n=8). This finding suggests that ET-1 is involved in the pathogenesis of diabetic microangiopathy. Study IV The effect of L-arginine and tetrahydrobiopterin (BH4) infusion on ischemia/reperfusion (I/R)-induced endothelial dysfunction following 20 minutes of forearm ischemia was studied in 12 patients with type 2 diabetes and coronary artery disease. L-arginine and BH4 significantly attenuated I/R-induced endothelial dysfunction in comparison with placebo. Conclusions The present studies of patients with type 2 diabetes and vascular complications indicate that 1) lipid lowering is more important than the pleiotropic effects of statins for the improvement in macrovascular endothelial function and microvascular function and the reduction in inflammation, 2) targeting the ET-1 system might be of importance in the treatment of complications related to diabetic microangiopathy and 3) supplementation with L-arginine and BH4 may represent a future treatment strategy to limit the I/R injury in patients with type 2 diabetes

The endothelin-1 receptor antagonist bosentan protects against ischaemia/reperfusion-induced endothelial dysfunction in humans. Clin Sci (Lond) 108

A B S T R A C T Endothelial dysfunction may contribute to the extent of ischaemia/reperfusion injury. ET (endothelin)-1 receptor antagonism protects against myocardial ischaemia/reperfusion injury in animal models. The present study investigated whether oral administration of an ET A /ET B receptor antagonist protects against ischaemia/reperfusion-induced endothelial dysfunction in humans. FBF (forearm blood flow) was measured with venous occlusion plethysmography in 13 healthy male subjects. Forearm ischaemia was induced for 20 min followed by 60 min of reperfusion. Using a cross-over protocol, the subjects were randomized to oral administration of 500 mg of bosentan or placebo 2 h before ischaemia. Endothelium-dependent and -independent vasodilatation were determined by intra-brachial infusion of acetylcholine (1-10 µg/min) and nitroprusside (0.3-3 µg/ min) respectively, before and after ischaemia. Compared with pre-ischaemia, the endotheliumdependent increase in FBF was significantly impaired at 15 and 30 min of reperfusion when the subjects received placebo (P < 0.01). When the subjects received bosentan, the endotheliumdependent increase in FBF was not affected by ischaemia/reperfusion. Endothelium-independent vasodilatation was not affected during reperfusion compared with pre-ischaemia. The vasoconstrictor response induced by intra-arterial infusion of ET-1 was attenuated significantly by bosentan (P < 0.001). The results suggest that the dual ET A /ET B receptor antagonist bosentan attenuates ischaemia/reperfusion-induced endothelial dysfunction in humans in vivo. Bosentan may thus be a feasible therapeutic agent in the treatment of ischaemia/reperfusion injury in humans

Effect of Postconditioning on Infarct Size in Patients With ST-elevation Myocardial Infarction

Background Small studies suggest that postconditioning reperfusion interrupted by brief repetitive cycles of reocclusions, may protect the myocardium in the clinical setting. Objective To test the hypothesis that postconditioning limits infarct size in relation to the area at risk in patients with ST elevation myocardial infarction (STEMI). Methods 76 patients (aged 37-87 years) eligible for primary percutaneous coronary intervention due to STEMI were randomised to standard percutaneous coronary intervention (n=38) or postconditioning, consisting of four cycles of 60 s reperfusion and 60 s of reocclusion before permanent reperfusion (n=38). Results The area at risk was determined from angiographic abnormally contracting segments. Infarct size was quantified from delayed enhancement MRI on days 6-9. Infarct size, expressed in relation to the area at risk, did not differ between the control group (44%; 30, 56) (median and quartiles) and the post-conditioned group (47%; 23, 63). The slope of the regression lines relating infarct size to the area at risk differed between the two groups. Infarct size was significantly (p=0.001) reduced by postconditioning in patients with large areas at risk. The area under the curve and peak troponin T release and CKMB during 48 h did not differ between patients in the control and postconditioning groups. Conclusions This prospective, randomised trial suggests that postconditioning does not reduce infarct size in patients with STEMI in the overall study group. The data indicate that postconditioning may be of value in patients with large areas at risk

Change in mitral regurgitation severity impacts survival after transcatheter aortic valve replacement

Background: The impact of a change in mitral regurgitation (MR) following TAVR is unknown. We studied the impact of baseline MR and early post-procedural change in MR on survival following TAVR. Methods: The SWEDEHEART registry included all TAVRs performed in Sweden. Patients were dichotomized into no/mild and moderate/severe MR groups. Vital status, echocardiographic data at baseline and within 7 days after TAVR were analyzed. Results: 1712 patients were included. 1404 (82%) had no/mild MR and 308 (18%) had moderate/severe MR. Baseline moderate/severe MR conferred a higher mortality rate at 5-year follow-up (adjusted HR 1.29, CI 1.01–1.65, p = 0.04). Using persistent ≤mild MR as the reference, when moderate/severe MR persisted or if MR worsened from ≤mild at baseline to moderate/severe after TAVR, higher 5-year mortality rates were seen (adjusted HR 1.66, CI 1.17–2.34, p = 0.04; adjusted HR 1.97, CI 1.29–3.00, p = 0.002, respectively). If baseline moderate/severe MR improved to ≤mild after TAVR no excess mortality was seen (HR 1.09, CI 0.75–1.58, p = 0.67). Paravalvular aortic regurgitation (PVL) was inversely associated with MR improvement after TAVR (OR 0.4, 95%: CI 0.17–0.94; p = 0.034). Atrial fibrillation (OR 2.1, 95% CI: 1.27–3.39, p = 0.004), self-expanding valve (OR 3.8, 95% CI: 2.08–7.14, p < 0.0001), and PVL (4.3, 95% CI 2.32–7.78. p < 0.0001) were associated with MR worsening. Conclusions: Moderate/severe baseline MR in patients undergoing TAVR is associated with a mortality increase during 5 years of follow-up. This risk is offset if MR improves to ≤mild, whereas worsening of MR after TAVR is associated with a 2-fold mortality increase

Characteristics and outcomes of patients receiving a second rescue valve during transcatheter aortic valve implantation

Background: Transcatheter aortic valve implantation (TAVI) has become a safe procedure. However, complications occur, including uncommon complications such as valve malposition, which requires the implantation of an additional rescue valve (rescue-AV). The aim was to study the occurrence and outcomes of rescue-AV in a nationwide registry. Methods: The Swedish national TAVI registry was used as the primary data source, where all 6706 TAVI procedures from 2016 to 2021 were retrieved. Nontransfemoral access and planned valve-in-valve were excluded. In total, 79 patients were identified as having had a rescue-AV, and additional detailed data were collected for these patients. This dataset was analyzed for any characteristics that could predispose patients to a rescue-AV. The outcome of patients receiving rescue-AV also was studied. Results: Of the 5948 patients in the study, 1.3% had a rescue-AV. There were few differences between patients receiving 1 valve and rescue-AV patients. For patients receiving a rescue-AV, the 30-day mortality was 15.2% compared to 1.6% in the control group. A poor outcome after rescue-AV was often associated with a second complication; for example, stroke, need for emergency surgery, or heart failure. Among the patients with rescue-AV who survived at least 30 days, landmark analyses showed similar survival rates compared to the control group. Conclusions: Among TAVI patients in a nationwide register, rescue-AV occurred in 1.3% of patients. The 30-day mortality in patients receiving rescue-AV was high, but long-term outcome among 30-day survivors was similar to the control group

Calcium Load in the Aortic Valve, Aortic Root, and Left Ventricular Outflow Tract and the Risk for a Periprocedural Stroke

Background: Periprocedural stroke during transcatheter aortic valve implantation is a rare but devastating complication. The calcified aortic valve is the most likely source of the emboli in a periprocedural stroke. The total load and distribution of calcium in the leaflets, aortic root, and left ventricular outflow tract varies from patient to patient. Consequently, there could be patterns of calcification that are associated with a higher risk of stroke. This study aimed to explore whether the pattern of calcification in the left ventricular outflow tract, annulus, aortic valve, and ascending aorta can be used to predict a periprocedural stroke. Methods: Among the 3282 consecutive patients who received a transcatheter aortic valve implantation in the native valve in Sweden from 2014 to 2018, we identified 52 who had a periprocedural stroke. From the same cohort, a control group of 52 patients was constructed by propensity score matching. Both groups had one missing cardiac computed tomography, and 51 stroke and 51 control patients were blindly reviewed by an experienced radiologist. Results: The groups were well balanced in terms of demographics and procedural data. Of the 39 metrics created to describe calcium pattern, only one differed between the groups. The length of calcium protruding above the annulus was 10.6 mm (interquartile range 7-13.6) for patients without stroke and 8 mm (interquartile range 3-10) for stroke patients. Conclusions: This study could not find any pattern of calcification that predisposes for a periprocedural stroke