| 1. |
- Appelblad, Micael, 1961-
(author)
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Fat contamination of pericardial suction blood in cardiac surgery : clinical and experimental studies in perspectives of transfusion logistics
- 2006
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Doctoral thesis (other academic/artistic)abstract
- Introduction: During cardiac surgery aided by cardiopulmonary bypass (CPB) the autotransfusion of pericardial suction blood (PSB) is regarded mandatory to limit allogeneic blood exposure. PSB is however proposed as a source of lipid microemboli and to contribute to brain damage. This thesis addresses the logistics of allogeneic blood transfusion during coronary artery bypass grafting (CABG), the embolic potential of reinfused PSB, and means to reduce PSB fat contamination, investigated both clinically and experimentally. Methods: Study I) Patients undergoing CABG surgery (n=2469) were included in a database study. The magnitude of surgical bleeding versus blood transfusion was analyzed to extract a subgroup of patients (n=982) in whom transfusions were independent from bleeding. Study II) PSB and venous-blood samples were collected from patients undergoing routine CABG (n=20). The in vitro capillary-flow properties of blood subcomponents and the effects of routine screen filtration were tested. PSB fat contamination was evaluated by imprint microscopy. Study III) Heat extracted liquid human fat or soya oil were mixed with mediastinal drain blood (n=20) and incubated in a temperature controlled column, to evaluate spontaneous density separation of fat. Study IV) The findings from study-III were applied to develop a fat-reducing system (FRS) using two stacked compartments. The FRS was experimentally tested (n=12), with similar methods as in study-III, and clinically evaluated (n=10). A single-chamber blood bag (n=10) served as reference. Results: Study I) A surgical bleeding of less than 400 mL showed no correlation to blood transfusion, although 64 of 982 patients still received allogeneic blood. The strongest predictors for this kind of transfusion were; female gender, weight ≤70 kg, CPB time ≥90 minutes, CPB temperature ≤32 ºC, and advanced age (P<.001 - .038). Study II) The capillary-flow profile of PSB plasma was highly impaired compared to venous plasma (P<.001). Conversely, blood-cell components showed no difference between PSB and venous blood. Routine screen filtration showed no ameliorating effect on capillary-flow resistance. Fat debris was detected on imprints in all PSB samples in contrast to venous plasma (P<.05). Study III) After 10-min of incubation had 77% of added soya oil separated and found contained in the top 20% fraction of blood (P<.001), aimed to be discarded. The density separation of human fat was less efficient compared to soya oil (P=.011). Fat also adsorbed to surface which was more pronounced at low temperature (P<.001). The overall reduction of human fat was 70%. Study IV) PSB contained 1.5 mL fat suspended in 418 mL PSB. Of this fat was 24% surface-bound. Experimental analysis of the proposed FRS revealed an 83% fat-reduction which was clinically confirmed, suggesting 80% reduction (P=.001). The FRS also gave a small but significant erythrocyte-concentrating effect. Conclusions: Transfusion of allogeneic blood during CABG surgery appeared associated with an institutional, individual, and technical bias of an anticipated need and not only used to compensation for surgical bleeding. In part may this reflect a non-compliant CPB methodology and hemodilution. It was confirmed that PSB plasma contained fat, with a suggested embolic potential. Human fat was significantly reduced from mediastinal drain blood by spontaneous density separation and surface adsorption. The prototype FRS used for PSB incubation during CPB allowed an efficient fat reduction.
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| 2. |
- Arefalk, Gabriel, et al.
(author)
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Smokeless Tobacco (Snus) and Risk of Heart Failure of Ischemic and Non-Ischemic Origin: a Pooled Analysis of Eight Prospective Cohort Studies
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Other publication (other academic/artistic)abstract
- BackgroundSnus, a Swedish type of smokeless tobacco, has potent acute hemodynamic effects, which could provoke stress on the cardiovascular system, including the myocardium. Snus has, however, not been linked to risk of ischemic heart disease. Therefore, we hypothesized that snus use increases the risk for heart failure of non-ischemic origin.MethodsWe conducted a pooled analysis of eight Swedish prospective cohort studies involving individual participant data from 350,711 men. Shared frailty models with random effects at the cohort level, were used to estimate hazard ratios (HRs) with 95 % confidence intervals (CIs) of heart failure in relation to snus use. We investigated dose-response associations, and association with ischemic and non-ischemic heart failure in separate. For positive control purposes, we also investigated associations between smoking and risk of heart failure.ResultsDuring a median follow-up time of 16 years, 5,404 men were hospitalized for heart failure. In models adjusting for age, smoking, previous myocardial infarction and educational level, current snus use was associated with a higher risk of heart failure (HR 1.27, 95 % CI 1.07-1.50), relative to non-current snus use. A dose-response pattern was observed, with higher risk with more snus cans used per week. We observed an association of snus use with non-ischemic heart failure, HR 1.34 (95 % CI 1.11-1.63), but not with ischemic heart failure, HR 1.01 (95 % CI 0.72-1.42). Smoking was more strongly associated with heart failure, particularly of ischemic origin, than snus use.ConclusionsSnus use was associated with a modestly increased risk for heart failure of non-ischemic origin in a dose-response manner. This finding has public health implications for the risk assessment of snus use, and potentially other modes of smokeless use of nicotine.
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| 3. |
- Bajraktari, Gani, et al.
(author)
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Combined electrical and global markers of dyssynchrony predict clinical response to Cardiac Resynchronization Therapy
- 2014
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In: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1401-7431 .- 1651-2006. ; 48:5, s. 304-310
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Journal article (peer-reviewed)abstract
- AIM: To assess potential additional value of global left ventricular (LV) dyssynchrony markers in predicting cardiac resynchronization therapy (CRT) response in heart failure (HF) patients. METHODS: We included 103 HF patients (mean age 67 +/- 12 years, 83% male) who fulfilled the guidelines criteria for CRT treatment. All patients had undergone full clinical assessment, NT-proBNP and echocardiographic examination. Global LV dyssynchrony was assessed using total isovolumic time (t-IVT) and Tei index. On the basis of reduction in the NYHA class after CRT, patients were divided into responders and non-responders. RESULTS: Prolonged t-IVT [0.878 (range, 0.802-0.962), p = 0.005], long QRS duration [0.978 (range, 0.960-0.996), p = 0.02] and high tricuspid regurgitation pressure drop [1.047 (range, 1.001-1.096), p = 0.046] independently predicted response to CRT. A t-IVT >= 11.6 s/min was 67% sensitive and 62% specifi c (AUC 0.69, p = 0.001) in predicting CRT response. Respective values for a QRS >= 151 ms were 66% and 62% (AUC 0.65, p = 0.01). Combining the two variables had higher specifi city (88%) in predicting CRT response. In atrial fibrillation (AF) patients, only prolonged t-IVT [0.690 (range, 0.509 -0.937), p = 0.03] independently predicted CRT response. CONCLUSION: Combining prolonged t-IVT and the conventionally used broad QRS duration has a significantly higher specifi city in identifying patients likely to respond to CRT. Moreover, in AF patients, only prolonged t-IVT independently predicted CRT response.
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| 4. |
- Bajraktari, Gani, 1964-
(author)
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The clinical value of total isovolumic time
- 2014
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Doctoral thesis (other academic/artistic)abstract
- The objective of this thesis is to evaluate the use of Doppler echocardiography markers ofglobal dyssynchrony [total isovolumic time (t-IVT)] in the following 6 studies: 1) Its prognostic role in predicting cardiac events in patients undergoing CABG surgery,compared with conventional global systolic and diastolic measurements. 2) Its additional value in predicting six minute walk test (6-MWT) in patients with leftventricular (LV) ejection fraction (EF) <45%. 3) Its prognostic value in comparison with other clinical, biochemical and echocardiographicvariables in patients with chronic systolic heart failure (HF). 4) The relationship between 6-MWT and cardiac function measurements in a consecutivegroup of patients, irrespective of EF and to identify predictors of exercise capacity. 5) To investigate the effect of age on LV t-IVT and Tei index compared with conventionalsystolic and diastolic parameters. 6) To assess potential additional value of markers of global LV dyssynchrony in predictingcardiac resynchronization therapy (CRT) response in HF patients.Study IMethods: This study included 74 patients before routine CABG who were followed up for18±12 months. Results: At follow-up, 29 patients were hospitalized for a cardiac event or died. LV-ESD wasgreater (P=0.003), fractional shortening (FS) lower (p<0.001), E:A ratio and Tei index higher(all P<0.001), and t-IVT longer (P<0.001) in patients with events. Low FS [0.66 (0.50–0.87),P<0.001], high E:A ratio [l4.13 (1.17–14.60), P=0.028], large LV-ESD [0.19 (0.05–0.84),P=0.029], and long t-IVT [1.37 (1.02–1.84), P=0.035] predicted events and deaths. Conclusion: Despite satisfactory surgical revascularization, long t-IVT and systolicdysfunction suggest persistent ventricular dyssynchrony that contributes to post-CABGcardiac events.Study IIMethods: We studied 77 patients (60±12 year, and 33.3% females) with stable HF using 6-MWT.iii Results: E’ wave (r=0.61, p<0.001), E/e’ ratio (r=-0.49, p<0.001), t-IVT (r=-0.44, p<0.001),Tei index (r=-0.43, p<0.001) and NYHA class (r=-0.53, p<0.001) had the highest correlationwith the 6-MWT distance. In multivariate analysis, only E/e’ ratio [0.800 (0.665-0.961),p=0.017], and t-IVT [0.769 (0.619-0.955), p=0.018] independently predicted poor 6-MWTperformance (<300m). Conclusions: In HF, the higher the filling pressures and the more dyssynchronous the LV, thepoorer is the patient’s exercise capacity.Study IIIMethods: We studied 107 systolic HF patients; age 68±12 year, 25% females and measuredplasma NT-pro-BNP. Results: Over a follow-up period of 3718 months, t-IVT ≥12.3 sec/min, mean E/Em ratio≥10, log NT-pro-BNP levels ≥2.47 pg/ml and LV EF ≤32.5% predicted clinical events. Theaddition of t-IVT and NT-pro-BNP to conventional clinical and echocardiographic variablessignificantly improved the χ2 for the prediction of outcome from 33.1 to 38.0, (p<0.001). Conclusions: Prolonged t-IVT adds to the prognostic stratification of patients with systolicHF.Study IVMethods: We studied 147 HF patients (61±11 year, 50.3% male) with 6-MWT.Results: The 6-MWT correlated with t-IVT (r=-0.49, p<0.001) and Tei index (r=-0.43,p<0.001) but not with any of the other clinical or echocardiographic parameters. Group Ipatients (<300m) had lower Hb (p=0.02), lower EF (p=0.003), larger left atrium (p=0.02),thicker septum (p=0.02), lower A wave (p=0.01) and lateral wall a’ (p=0.047), longerisovolumic relaxation time (r=0.003) and longer t-IVT (p= 0.03), compared with Group II(>300m). Only t-IVT ratio [1.257 (1.071-1.476), p=0.005], LV EF [0.947 (0.903-0.993),p=0.02], and E/A ratio [0.553 (0.315-0.972), p=0.04] independently predicted poor 6-MWTperformance. Conclusion: In HF, the limited 6-MWT is related mostly to severity of global LVdyssynchrony, more than EF or raised filling pressures.Study VMethods: We studied 47 healthy individuals (age 62±12 year, 24 female), arbitrarilyclassified into: M (middle age), S (seniors), and E (elderly). Results: Age strongly correlated with t-IVT (r=0.8, p<0.001) and with Tei index (r=0.7,p<0.001), E/A ratio (r=-0.6, p<0.001), but not with global or segmental systolic function measurements or QRS duration. The normal upper limit of the t-IVT (95% CI) for the three groups was 8.3 s/min, 10.5 s/min and 14.5 s/min, respectively, being shorter in the S compared with the E group (p=0.001). T-IVT correlated with A wave (r=0.66, p<0.001), E/Aratio (r=-0.56, p<0.001), septal e’ (r=-0.49, p=0.001) and septal a’ (r=0.4, p=0.006), but notwith QRS. Conclusions: In normals, age is associated with exaggerated LV global dyssynchrony anddiastolic function disturbances, but systolic function remains unaffected.Study VIMethods: We studied 103 HF patients (67±12 year, 82.5% male) recruited for CRTtreatment. Results: Prolonged t-IVT [0.878 (0.802-0.962), p=0.005], long QRS duration [0.978 (0.960-0.996), p=0.02] and high tricuspid regurgitation pressure drop (TRPD) [1.047 (1.001-1.096),p=0.046] independently predicted response to CRT. A t-IVT ≥11.6 s/min was 67% sensitiveand 62% specific (AUC 0.69, p=0.001) in predicting CRT response. Respective values for aQRS ≥ 151ms were 66% and 62% (AUC 0.65, p=0.01). Combining the two variables had asensitivity of 67% but higher specificity of 88% in predicting CRT response. In atrialfibrillation (AF) patients, only prolonged t-IVT ≥11 s/min [0.690 (0.509-0.937), p=0.03]independently predicted CRT response with a sensitivity of 69% and specificity of 79% (AUC0.78, p=0.015). Conclusion: Combining prolonged t-IVT and broad QRS had higher specificity in predictingresponse to CRT, with the former the sole predictor of response in AF patients.
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| 5. |
- Bergh, Niklas, 1979, et al.
(author)
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Estimating the clinical and budgetary impact of using angiotensin receptor neprilysin inhibitor as first line therapy in patients with HFrEF.
- 2024
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In: ESC Heart Failure. - 2055-5822. ; 11:2, s. 1153-1162
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Journal article (peer-reviewed)abstract
- Recent updates of international treatment guidelines for heart failure with reduced ejection fraction (HFrEF) differ regarding the use of angiotensin receptor neprilysin inhibitor (ARNI) as first-line treatment. The American Heart Association/American College of Cardiology/Heart Failure Society of America (AHA/ACC/HFSA) 2022 guidelines gives ARNI a Class IA recommendation for HFrEF patients while the European Society of Cardiology's guidelines are less clear when ARNI could be considered as first line treatment option in de novo patients. This study aimed to model the clinical and budgetary outcomes of implementing these guidelines, comparing conservative ARNI prescription patterns with less conservative in Sweden and in the United Kingdom.A health economic model was developed to compare different treatment patterns for HFrEF. Incident cohorts were included on an annual basis and followed over 10years. The model included treatment specific all-cause mortality and hospitalization rates, as well as drug acquisition, monitoring, and hospitalization costs. Increasing the use of ARNI could lead to about 7000-12300 life years gained and 2600-4600 hospitalizations prevented in Sweden. These health benefits come with an additional cost of 112-195 million euros. Similar results were estimated for the United Kingdom, albeit on a larger population.Increasing the proportion of patients receiving ARNI instead of angiotensin converting enzyme inhibitors as first-line treatment of HFrEF will lead to a considerable number of additional life years gained and prevented hospitalizations but with additional cost in terms of health care expenditure in Sweden and in the United Kingdom.
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| 6. |
- Boman, Kurt, et al.
(author)
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Healthcare resource utilisation and costs associated with a heart failure diagnosis : A retrospective, population-based cohort study in Sweden
- 2021
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In: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 11:10
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Journal article (peer-reviewed)abstract
- Objectives: To examine healthcare resource use (HRU) and costs among heart failure (HF) patients using population data from Sweden.Design: Retrospective, non-interventional cohort study.Setting: Two cohorts were identified from linked national health registers (cohort 1, 2005-2014) and electronic medical records (cohort 2, 2010-2012; primary/secondary care patients from Uppsala and Västerbotten).Participants: Patients (aged ≥18 years) with primary or secondary diagnoses of HF (≥2 International Classification of Diseases and Related Health Problems, 10th revision classification) during the identification period of January 2005 to March 2015 were included.Outcome measures: HRU across the HF phenotypes was assessed with logistic regression. Costs were estimated based on diagnosis-related group codes and general price lists.Results: Total annual costs of secondary care of prevalent HF increased from SEK 6.23 (€0.60) to 8.86 (€0.85) billion between 2005 and 2014. Of 4648 incident patients, HF phenotype was known for 1715: reduced ejection fraction (HFrEF): 64.5%, preserved ejection fraction (HFpEF): 35.5%. Within 1 year of HF diagnosis, the proportion of patients hospitalised was only marginally higher for HFrEF versus HFpEF (all-cause (95% CI): 64.7% (60.8 to 68.4) vs 63.7% (60.8 to 66.5), HR 0.91, p=0.14; cardiovascular disease related (95% CI): 61.1% (57.1 to 64.8) vs 60.9% (58.0 to 63.7), HR 0.93, p=0.28). Frequency of hospitalisations and outpatient visits per patient declined after the first year. All-cause secondary care costs in the first year were SEK 122 758 (€12 890)/patient/year, with HF-specific care accounting for 69% of the costs. Overall, 10% of the most expensive population (younger; predominantly male; more likely to have comorbidities) incurred ~40% of total secondary care costs.Conclusions: HF-associated costs and HRU are high, especially during the first year of diagnosis. This is driven by high hospitalisations rates. Understanding the profile of resource-intensive patients being at younger age, male sex and high Charlson comorbidity index scores at the time of the HF diagnosis is most likely a sign of more severe disease.
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| 7. |
- Boman, Kurt, et al.
(author)
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Healthcare resource utilization associated with heart failure with preserved versus reduced ejection fraction : a retrospective population-based cohort study in Sweden
- 2017
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In: European Journal of Heart Failure. - : European Society of Cardiology. - 1388-9842 .- 1879-0844. ; 19:S1, s. 346-346
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Journal article (peer-reviewed)abstract
- Background and purpose: To estimate healthcare resource utilization among patients with heart failure (HF) with preserved (HFpEF) versus reduced (HFrEF) ejection fraction using population data from two Swedish counties.Methods: Patients with HF were identified via electronic medical records (EMRs) from primary and/or secondary care in Uppsala and Västerbotten, linked via unique identifiers to data from the National Patient Register and Swedish Prescribed Drug Register. Local echocardiography data were used to identify HFpEF (defined as ejection fraction ≥50%) and HFrEF (defined as <50%). Patients aged ≥18 years with ≥2 diagnoses of HF between 01/01/2010 and 31/03/2015 and an ICD-10 diagnostic code of I50 (inclusive of all granular codes), I42.0, I42.6, I42.7, I42.9, I110, I130 or I132 in any position were included. Patients were followed from date of first diagnosis (index date) to end of study period or EMR collection, date of death or loss to follow-up for other reasons, whichever came first. Unadjusted all-cause and cardiovascular disease (CVD)-related hospitalization rates were assessed using a Cox proportional hazards model, accounting for age, sex, setting of first diagnosis (primary vs secondary care), HF phenotype and NT-proBNP level.Results: In total, 8702 patients with HF were identified. HF phenotype was known in 3167 patients; 64.6% had HFrEF, 35.4% had HFpEF. Patients with HFrEF were younger (mean±SD: 69.9±13.7 vs 74.2±12.6 years) with a lower Charlson comorbidity index (1.65 vs 1.83) than those with HFpEF. All-cause hospitalization rates were marginally lower for HFrEF than for HFpEF (mean [95% CI] proportion of patients hospitalized within 1 year of diagnosis, 72.5 [70.1–74.8]% vs 73.8 [70.7–77.0]%; hazard ratio [HR] over whole follow-up period, 0.87 [0.79–0.97], p=0.0093). The proportion of patients hospitalized was higher for those diagnosed in secondary care than in primary care, particularly within 1 year of diagnosis (1-year rate, 69.6 [68.3–71.0]% vs 59.1 [56.8–61.4]%; HR, 1.15 [1.07–1.23], p=0.0002). Similar trends were observed for CVD-related hospitalization rates for HFrEF vs HFpEF (1-year rate, 69.5 [67.1–71.9]% vs 70.7 [67.5–74.0]%; HR, 0.89 [0.81–0.99], p=0.0309) and for patients diagnosed in secondary vs primary care (1-year rate, 66.6 [65.3–68.0]% vs 56.2 [53.8–58.5]%; HR, 1.15 [1.07–1.24], p=0.0001). Numbers of hospitalizations and outpatient visits decreased with time after diagnosis for HFrEF, but increased slightly for HFpEF after 2 years (Figure). The mean±SD total number of all-cause days of hospitalization during the first year after diagnosis was lower in patients with HFrEF vs HFpEF (19.9±26.1 vs 26.3±34.5 days), while the number of HF-related days of hospitalization was similar (16.0±22.4 vs 17.2±24.0 days).Conclusions: Number and duration of hospital stays were significantly lower over time in patients with HFrEF than HFpEF; this may be explained by the comorbidity burden in the latter group.
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| 8. |
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| 9. |
- Fonseca-Rodríguez, Osvaldo, et al.
(author)
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Avoiding bias in self-controlled case series studies of coronavirus disease 2019
- 2021
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In: Statistics in Medicine. - : John Wiley & Sons. - 0277-6715 .- 1097-0258. ; 40:27, s. 6197-6208
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Journal article (peer-reviewed)abstract
- Many studies, including self-controlled case series (SCCS) studies, are being undertaken to quantify the risks of complications following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19). One such SCCS study, based on all COVID-19 cases arising in Sweden over an 8-month period, has shown that SARS-CoV-2 infection increases the risks of AMI and ischemic stroke. Some features of SARS-CoV-2 infection and COVID-19, present in this study and likely in others, complicate the analysis and may introduce bias. In the present paper we describe these features, and explore the biases they may generate. Motivated by data-based simulations, we propose methods to reduce or remove these biases.
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| 10. |
- Fu, Michael, 1963, et al.
(author)
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Implementation of sacubitril/valsartan in Sweden: clinical characteristics, titration patterns, and determinants
- 2020
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In: Esc Heart Failure. - : Wiley. - 2055-5822.
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Journal article (peer-reviewed)abstract
- Aims The aim of this study is to study the introduction of sacubitril/valsartan (sac/val) in Sweden with regards to regional differences, clinical characteristics, titration patterns, and determinants of use and discontinuation. Methods and results A national cohort of heart failure was defined from the Swedish Prescribed Drug Register and National Patient Register. A subcohort with additional data from the Swedish Heart Failure Registry (SwedeHF) was also studied. Cohorts were subdivided as per sac/val prescription and registration in SwedeHF. Median sac/val prescription rate was 20 per 100 000 inhabitants. Between April 2016 and December 2017, we identified 2037 patients with >= 1 sac/val prescription, of which 1144 (56%) were registered in SwedeHF. Overall, patients prescribed with sac/val were younger, more frequently male, and had less prior cardiovascular disease than non-sac/val patients. In SwedeHF subcohort, patients prescribed with sac/val had lower ejection fraction. Overall, younger age [hazard ratio 2.81 (95% confidence interval 2.45-3.22)], registration in SwedeHF [1.97 (1.83-2.12)], male gender [1.50 (1.37-1.64)], ischaemic heart disease [1.50 (1.39-1.62)], lower left ventricular ejection fraction [3.06 (2.18-4.31)], and New York Heart Association IV [1.50 (1.22-1.84)] were predictors for sac/val use. As initiation dose in the sac/val cohort, 38% received 24/26 mg, 54% 49/51 mg, and 9% 97/103 mg. Up-titration to the target dose was achieved in 57% of the overall cohort over a median follow-up of 6 months. The estimated treatment persistence for any dose at 360 days was 82%. Conclusions Implementation of sac/val in Sweden was slow and varied five-fold across different regions; younger age, male, SwedeHF registration, and ischaemic heart disease were among the independent predictors of receiving sac/val. Overall, treatment persistence and tolerability was high.
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