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  • 151. Cadilhac, Dominique A.
    et al.
    Amatya, Bhasker
    Lalor, Erin
    Rudd, Anthony
    Lindsay, Patrice
    Asplund, Kjell
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Is There Evidence That Performance Measurement in Stroke Has Influenced Health Policy and Changes to Health Systems?2012In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 43, no 12, p. 3413-3420Article, review/survey (Refereed)
  • 152.
    Calcutteea, Avin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    New insights in the assessment of right ventricular function: an echocardiographic study2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background:  The right ventricle (RV) is multi-compartmental in orientation with a complex structural geometry. However, assessment of this part of the heart has remained an elusive clinical challenge. As a matter of fact, its importance has been underestimated in the past, especially its role as a determinant of cardiac symptoms, exercise capacity in chronic heart failure and survival in patients with valvular disease of the left heart. Evidence also exists that pulmonary hypertension (PH) affects primarily the right ventricular function. On the other hand, previous literature suggested that severe aortic stenosis (AS) affects left ventricular (LV) structure and function which partially recover after aortic valve replacement (AVR). However, the impact of that on RV global and segmental function remains undetermined. 

    Objectives: We sought to gain more insight into the RV physiology using 3D technology, Speckle tracking as well as already applicable echocardiographic measures. Our first aim was to assess the normal differential function of the RV inflow tract (IT), apical and outflow tract (OT) compartments, also their interrelations and the response to pulmonary hypertension. We also investigated the extent of RV dysfunction in severe AS and its response to AVR. Lastly, we studied the extent of global and regional right ventricular dysfunction in patients with pulmonary hypertension of different aetiologies and normal LV function.

    Methods: The studies were performed on three different groups; (1) left sided heart failure with (Group 1) and without (Group 2) secondary pulmonary hypertension, (2) severe aortic stenosis and six months post AVR and (3) pulmonary hypertension of different aetiologies and normal left ventricular function. We used 3D, speckle tracking echocardiography and conventionally available Doppler echocardiographic transthoracic techniques including M-mode, 2D and myocardial tissue Doppler. All patients’ measurements were compared with healthy subjects (controls). Statistics were performed using a commercially available SPSS software.

    Results:

    1-  Our RV 3D tripartite model was validated with 2D measures and eventually showed strong correlations between RV inflow diameter (2D) and end diastolic volume (3D) (r=0.69, p<0.001) and between tricuspid annular systolic excursion (TAPSE) and RV ejection fraction (3D) (r=0.71, p<0.001). In patients (group 1 & 2) we found that the apical ejection fraction (EF) was less than the inflow and outflow (controls:  p<0.01 & p<0.01, Group 1:  p<0.05 & p<0.01 and Group 2: p<0.05 & p<0.01, respectively). Ejection fraction (EF) was reduced in both patient groups (p<0.05 for all compartments). Whilst in controls, the inflow compartment reached the minimum volume 20 ms before the outflow and apex, in Group 2 it was virtually simultaneous. Both patient groups showed prolonged isovolumic contraction (IVC) and relaxation (IVR) times (p<0.05 for all). Also, in controls, the outflow tract was the only compartment where the rate of volume fall correlated with the time to peak RV ejection (r = 0.62, p = 0.03). In Group 1, this relationship was lost and became with the inflow compartment (r = 0.61, p = 0.01). In Group 2, the highest correlation was with the apex (r=0.60, p<0.05), but not with the outflow tract.

    2- In patients with severe aortic stenosis, time to peak RV ejection correlated with the basal cavity segment (r = 0.72, p<0.001) but not with the RVOT. The same pattern of disturbance remained after 6 months of AVR (r = 0.71, p<0.001). In contrast to the pre-operative and post-operative patients, time to RV peak ejection correlated with the time to peak outflow tract strain rate (r = 0.7, p<0.001), but not with basal cavity function. Finally in patients, RVOT strain rate (SR) did not change after AVR but basal cavity SR fell  (p=0.04).

    3- In patients with pulmonary hypertension of different aetiologies and normal LV function, RV inflow and outflow tracts were dilated (p<0.001 for both). Furthermore, TAPSE (p<0.001), inflow velocities (p<0.001), basal and mid-cavity strain rate (SR) and longitudinal displacement (p<0.001 for all) were all reduced. The time to peak systolic SR at basal, mid-cavity (p<0.001 for both) and RVOT (p=0.007) was short as was that to peak displacement (p<0.001 for all). The time to peak pulmonary ejection correlated with time to peak SR at RVOT (r=0.7, p<0.001) in controls, but with that of the mid cavity in patients (r=0.71, p<0.001). Finally, pulmonary ejection acceleration (PAc) was faster (p=0.001) and RV filling time shorter in patients (p=0.03) with respect to controls.

    Conclusion: RV has distinct features for the inflow, apical and outflow tract compartments, with different extent of contribution to the overall systolic function. In PH, RV becomes one dyssynchronous compartment which itself may have perpetual effect on overall cardiac dysfunction. In addition, critical aortic stenosis results in RV configuration changes with the inflow tract, rather than outflow tract, determining peak ejection. This pattern of disturbance remains six month after valve replacement, which confirms that once RV physiology is disturbed it does not fully recover. The findings of this study suggest an organised RV remodelling which might explain the known limited exercise capacity in such patients. Furthermore, in patients with PH of different aetiologies and normal LV function, there is a similar pattern of RV disturbance. Therefore, we can conclude that early identification of such changes might help in identifying patients who need more aggressive therapy early on in the disease process.

  • 153.
    Calcutteea, Avin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Holmgren, Anders
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Organised right ventricular remodelling in aortic stenosis even after valve replacement2013In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 168, no 2, p. 1549-1550Article in journal (Refereed)
  • 154.
    Calcutteea, Avin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Global and regional right ventricular disturbances in pulmonary hypertensionArticle in journal (Other academic)
  • 155.
    Calcutteea, Avin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Umeå Heart Center.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Umeå Heart Center.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Umeå Heart Center.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Umeå Heart Center.
    Global and regional right ventricular dysfunction in pulmonary hypertension2014In: Echocardiography, ISSN 0742-2822, E-ISSN 1540-8175, Vol. 31, no 2, p. 164-171Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Pulmonary hypertension (PH) is known to affect the right ventricular (RV) function.

    AIMS: To assess the extent of global and regional RV dysfunction in PH patients.

    METHODS: We performed a cross-sectional study on 20 controls (age 62 ± 15 years, 7 males) and 35 patients (age 67 ± 12 years, 13 males) with PH of mixed etiologies and assessed RV inflow and outflow tracts (OTs) function, using speckle tracking echocardiography (STE) based myocardial deformation and its time relations. RV inlet and OT dimensions (2D), inlet myocardial velocities (TDI), myocardial strain and strain rate (SR), TAPSE (M-mode), ejection and filling times (pulsed-wave [PW] Doppler), and pulmonary artery acceleration (PAc) were measured.

    RESULTS: RV inlet and OT were dilated (P < 0.001 for both) and TAPSE (P < 0.001), inlet velocities (P < 0.001), basal and mid-cavity strain, SR and longitudinal displacement reduced (P < 0.001 for all). The time to peak systolic SR at basal, mid-cavity (P < 0.001 for both), and RVOT (P = 0.007) was short as was that to peak displacement (P < 0.001 for all). The time to peak pulmonary ejection correlated with time to peak SR at RVOT (r = 0.7, P < 0.001) in controls, but with that of the mid-cavity in patients (r = 0.71, P < 0.001). PAc was faster (P = 0.001) and RV filling time shorter in patients (P = 0.03) with respect to controls.

    CONCLUSIONS: PH has drastic effects on RV structure and intrinsic myocardial function, significantly disturbing its ejection time relations and overall pump performance. Increased RV afterload results in RV configuration changes with the inflow tract determining peak ejection rather than OT.

  • 156. Cameli, M.
    et al.
    Lisi, M.
    Reccia, R.
    Bigio, E.
    Bennati, E.
    Malandrino, A.
    Maccherini, M.
    Chiavarelli, M.
    Henein, Michael Y.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Mondillo, S.
    Left atrial strain predicts postoperative atrial fibrillation in patients waiting for aortic valve replacement for aortic stenosis2012In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 33, no Suppl. 1, p. 826-826Article in journal (Other academic)
  • 157. Cameli, M.
    et al.
    Mondillo, S.
    Righini, F. M.
    Lisi, M.
    Sparla, S.
    Di Tommaso, C.
    Marino, F.
    Tsioulpas, C.
    Maccherini, M.
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Left ventricular deformation accurately predicts the extent of myocardial fibrosis in patients with advanced heart failure requiring transplantation2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no Suppl 1, p. 835-835Article in journal (Other academic)
  • 158. Cameli, M.
    et al.
    Righini, F. M.
    Lisi, M.
    Di Tommaso, C.
    Curci, V.
    Navarri, R.
    Lunghetti, S.
    Focardi, M.
    Henein, Mark
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Mondillo, S.
    Left atrial strain for prognisis prediction of patients with moderate mitral valve regurgitation2014In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, no Supplement 1, Meeting abstract P1380, p. 243-243Article in journal (Other academic)
  • 159.
    Cameli, Matteo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Mechanical and histological disturbances in advanced heart failure and cardiac transplantation2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The general purpose of this thesis is to establish capability and accuracy of speckle tracking echocardiography (STE) in assessing left atrial (LA), left ventricular (LV) and right ventricular (RV) function and their correlation with myocardial fibrosis, filling pressure and clinical outcomes in advanced heart failure (HF) patients before and after heart transplantation (HT).

    I demonstrated that HT recipients had impaired LV twist dynamics in the form of reduced rotation twist angle and untwist rate but time to peak twist was not different from the age matched controls and other cardiac surgical patients.

    With a longitudinal study conducted on patients with refractory HF, the best prognostic power has been shown by RV strain analysis. Among the indexes of LV function, the LV ejection fraction (LVEF) demonstrated the lowest diagnostic accuracy; instead LV global circumferential strain (GCS) showed a better sensitivity and specificity than LV global longitudinal strain (GLS).

    When analyzing the relationship between different severity of myocardial fibrosis and LV cavity function, the strongest function parameter that correlated with severity of myocardial fibrosis was GLS. In contrast, none of diastolic LV function or even measures of exercise capacity correlated with myocardial fibrosis.

    In patients with end-stage HF, global peak atrial longitudinal strain (PALS), an index of atrial reservoir function was dependent by pulmonary capillary wedge pressure (PCWP) and LV fibrosis, but not influenced by LV systolic function. Results from this study confirm previous evidence of correlation between impaired global PALS and increased PCWP.

  • 160. Cameli, Matteo
    et al.
    Ballo, Piercarlo
    Lisi, Matteo
    Benincasa, Susanna
    Focardi, Marta
    Bernazzali, Sonia
    Lisi, Gianfranco
    Maccherini, Massimo
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Mondillo, Sergio
    Left ventricular twist in clinically stable heart transplantation recipients: a speckle tracking echocardiography study2013In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 168, no 1, p. 357-361Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIM: Cavity twist is an integral part of LV function and its pattern in transplanted hearts is not well known. This study aimed at exploring LV twist in clinically stable heart transplant (HT) recipients with no evidence for rejection.

    METHODS: We studied 32 HT patients (54±24months after HT), 34 other cardiac surgery (CS) patients and compared them with 35 health controls using speckle tracking echocardiography, measuring peak twist angle, time-to-peak twist, and untwist rate.

    RESULTS: LV twist angle was smaller in the HT group (6.2±3.3°) in comparison with the CS group and controls (13.2±3.5° and 13.1±4.5°, respectively; p<0.0001 for all) and untwist rate was reduced (HT group: -74±30°/s; CS group: -118±43°/s; controls: -116±39°/s; p<0.0001 for all). Time-to-peak twist was not different between groups. Time after HT was the main independent predictor of both LV twist angle and untwist rate (β=0.8, p<0.0001).

    CONCLUSION: Though clinically stable, LV twist dynamics are significantly impaired in HT recipients, even in comparison with patients who underwent other cardiac surgery.

  • 161.
    Cameli, Matteo
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Focardi, M.
    Bennati, E.
    Massoni, A.
    Loffreno, A.
    Carbone, S.
    Galderisi, M.
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Mondillo, S.
    Patients with suspicion of myocarditis and normal ejection fraction: role of speckle tracking echocardiography2014In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, no Supplement 1, Meeting abstract P5212, p. 919-920Article in journal (Other academic)
  • 162.
    Cameli, Matteo
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Lisi, Matteo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Reccia, Rosanna
    Bennati, Elena
    Malandrino, Angela
    Solari, Marco
    Bigio, Elisa
    Biagioli, Bonizella
    Righini, Francesca Maria
    Maccherini, Massimo
    Chiavarelli, Mario
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Mondillo, Sergio
    Pre-operative left atrial strain predicts post-operative atrial fibrillation in patients undergoing aortic valve replacement for aortic stenosis2014In: The International Journal of Cardiovascular Imaging, ISSN 1569-5794, E-ISSN 1875-8312, Vol. 30, no 2, p. 279-286Article in journal (Refereed)
    Abstract [en]

    Post-operative atrial fibrillation (AF) is a common and serious complication in patients undergoing aortic valve replacement (AVR). Speckle tracking echocardiography (STE) has recently enabled the quantification of longitudinal myocardial left atrial (LA) deformation dynamics. Our aim was to investigate LA preoperative mechanical function in patients undergoing AVR for aortic stenosis using STE and determine predictors of post-operative AF. 76 patients with aortic stenosis in sinus rhythm, undergoing AVR, were prospectively enrolled. Conventional echocardiographic parameters, and peak atrial longitudinal strain (PALS) were measured in all subjects the day before surgery. PALS values were obtained by averaging all segments in the 4- and 2-chamber views (global PALS). All patients received biological valve prostheses and a standard postoperative care. Postoperative AF occurred in 15 patients (19.7 %). On univariate analysis among all clinical and echocardiographic variables, global PALS showed the highest diagnostic accuracy (HR 6.55 p < 0.0001; AUC of 0.89) with a cut-off value < 16.9 %, having sensitivity and specificity of 86 and 91 %, respectively, in predicting postoperative AF. LA volume indexed and E/e' ratio had lower diagnostic accuracy (AUC 0.76 and 0.51, respectively). On multivariate analysis global PALS remains a significant predictor of postoperative AF (p < 0.0001). STE analysis of LA myocardial deformation is considered a promising tool for the evaluation of LA subclinical dysfunction in patients undergoing AVR, giving a potentially better risk stratification for the occurrence of postoperative AF.

  • 163.
    Cameli, Matteo
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Loiacono, Ferdinando
    Righini, Francesca M.
    Sparla, Stefania
    Mandoli, Giulia E.
    Dokollari, Aleksander
    Sassi, Carlo G.
    Bernazzali, Sonia
    Maccherini, Massimo
    Mondillo, Sergio
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Structure and functional predictors of left atrial pressure inpatients with end-stage heart failureManuscript (preprint) (Other academic)
  • 164. Cameli, Matteo
    et al.
    Mandoli, Giulia Elena
    Loiacono, Ferdinando
    Dini, Frank Lloyd
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Mondillo, Sergio
    Left atrial strain: a new parameter for assessment of left ventricular filling pressure2016In: Heart Failure Reviews, ISSN 1382-4147, E-ISSN 1573-7322, Vol. 21, no 1, p. 65-76Article in journal (Refereed)
    Abstract [en]

    In order to obtain accurate diagnosis, treatment and prognostication in many cardiac conditions, there is a need for assessment of left ventricular (LV) filling pressure. While systole depends on ejection function of LV, diastole and its disturbances influence filling function and pressures. The commonest condition that represents the latter is heart failure with preserved ejection fraction in which LV ejection is maintained, but diastole is disturbed and hence filling pressures are raised. Significant diastolic dysfunction results in raised LV end-diastolic pressure, mean left atrial (LA) pressure and pulmonary capillary wedge pressure, all referred to as LV filling pressures. Left and right heart catheterization has traditionally been used as the gold standard investigation for assessing these pressures. More recently, Doppler echocardiography has taken over such application because of its noninvasive nature and for being patient friendly. A number of indices are used to achieve accurate assessment of filling pressures including: LV pulsed-wave filling velocities (E/A ratio, E wave deceleration time), pulmonary venous flow (S wave and D wave), tissue Doppler imaging (E' wave and E/E' ratio) and LA volume index. LA longitudinal strain derived from speckle tracking echocardiography (STE) is also sensitive in estimating intracavitary pressures. It is angle-independent, thus overcomes Doppler limitations and provides highly reproducible measures of LA deformation. This review examines the application of various Doppler echocardiographic techniques in assessing LV filling pressures, in particular the emerging role of STE in assessing LA pressures in various conditions, e.g., HF, arterial hypertension and atrial fibrillation.

  • 165.
    Cameli, Matteo
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Department of Cardiovascular Diseases, University of Siena, Siena, Italy.
    Mondillo, Sergio
    Righini, Francesca Maria
    Lisi, Matteo
    Department of Cardiovascular Diseases, University of Siena, Siena, Italy.
    Dokollari, Aleksander
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Maccherini, Massimo
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Left Ventricular Deformation and Myocardial Fibrosis in Patients With Advanced Heart Failure Requiring Transplantation2016In: Journal of Cardiac Failure, ISSN 1071-9164, E-ISSN 1532-8414, Vol. 22, no 11, p. 901-907Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To evaluate potential relationships between different components of left ventricular (LV) function and histopathological evidence for myocardial fibrosis in patients undergoing heart transplantation.

    METHODS: The study population included patients with advanced heart failure, referred for an echocardiographic examination before heart transplantation. Traditional LV function measurements and global longitudinal strain (GLS) by speckle tracking echocardiography, averaging all LV segments in 4-, 2-, and 3-chamber views were obtained in all subjects. LV tissue samples were obtained from all patients who underwent heart transplantation. Myocardial fibrosis was assessed using Masson's staining.

    RESULTS: Of 106 patients referred for cardiac transplantation, 47 underwent cardiac transplantation and were enrolled in the study. LV myocardial fibrosis and its grade strongly correlated with GLS (r = 0.75, P = .0001), modestly with global circumferential strain and LV torsion (r = 0.61, P = .001 and r = 0.52, P = .01, respectively) and weakly with mitral S' wave (r = -0.41; P = .01) and mitral annular plane systolic excursion (r = -0.35; P = .05) but did not correlate with LV ejection fraction (r = -0.12; P = NS). GLS had the strongest accuracy for detecting LV fibrosis (area under the curve, 0.92). None of the echo parameters correlated with patient's exercise capacity.

    CONCLUSION: Global longitudinal strain is the most accurate LV global function measure that correlates with the extent of myocardial fibrosis in patients with advanced systolic HF requiring heart transplantation.

  • 166. Cameli, Matteo
    et al.
    Pastore, Maria Concetta
    De Carli, Giuseppe
    Henein, Michael Y.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. St George London & Brunel Universities, UK.
    Mandoli, Giulia Elena
    Lisi, Edoardo
    Cameli, Paolo
    Lunghetti, Stefano
    D'Ascenzi, Flavio
    Nannelli, Chiara
    Rizzo, Luisa
    Valente, Serafina
    Mondillo, Sergio
    ACUTE HF score, a multiparametric prognostic tool for acute heart failure: A real-life study2019In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 296, p. 103-108Article in journal (Refereed)
    Abstract [en]

    Background: Acute heart failure (AHF) is the first cause of hospitalization for over-65 individuals, associated with high mortality and readmission rate. The aim of this study was to assess the prognostic value of a multiparametric score combining clinical, biochemical and echocardiographic indexes in AHF for clinical practice.

    Methods: 830 patients hospitalized for AHF were enrolled. Exclusion criteria were: active neoplasms; previous heart transplantation or left ventricular assist device implantation. Different variables were analyzed: etiology of AHF, clinical and biochemical data, lung congestion on chest-X ray, echocardiographic parameters and administered therapy. The endpoints were: all-cause mortality at 30 days, 6 months and 5 years and the duration of hospitalization.

    Results: 771 patients met eligibility criteria. Using the univariate and multivariate analysis the indexes with the best correlation with outcome were discretized and used to create the ACUTE HF score, computed as: 1.4*[serum creatinine>2 mg/dl] + 0.8*[ejection fraction<30] + 0.7*[age > 76] + 0.7*[prior hospitalization for AHF] + 0.9*[prior stroke/transient ischemic attack] + 0.5*[more than moderate mitral regurgitation] + 0.8*[use of non-invasive ventilation] and used to divide patients into 3 groups according to the risk of 6-months mortality. With the receiver operating curves and Kaplan-Meier analysis, this score proved to have a high predictive power for mortality at 30 days, 6 months and 5 years from hospitalization, and for event-free survival rates, providing a risk stratification capability superior to that of single variables.

    Conclusions: The ACUTE HF score could be a complete and useful tool for assessing prognosis of AHF patients. It could represent a step in the long standardization pathway of prognostic protocols for AHF.

  • 167. Cameli, Matteo
    et al.
    Pastore, Maria Concetta
    Henein, Michael Y.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Mondillo, Sergio
    The left atrium and the right ventricle: two supporting chambers to the failing left ventricle2019In: Heart Failure Reviews, ISSN 1382-4147, E-ISSN 1573-7322, Vol. 24, no 5, p. 661-669Article in journal (Refereed)
    Abstract [en]

    Heart failure (HF) is mainly caused by left ventricular (LV) impairment of function, hence detailed assessment of its structure and function is a clinical priority. The frequent involvement of the left atrium (LA) and the right ventricle (RV) in the overall cardiac performance has recently gained significant interest with specific markers predicting exercise intolerance and prognosis being proposed. The LA and RV are not anatomically separated from the LV, while the LA controls the inlet the RV shares the interventricular septum with the LV. Likewise, the function of the two chambers is not entirely independent from that of the LV, with the LA enlarging to accommodate any rise in filling pressures, which could get transferred to the RV via the pulmonary circulation. In the absence of pulmonary disease, LA and RV function may become impaired in patients with moderate-severe LV disease and raised filling pressures. These changes can often occur irrespective of the severity of systolic dysfunction, thus highlighting the important need for critical assessment of the function of the two chambers. This review evaluates the pivotal role of the left atrium and right ventricle in the management of HF patients based on the available evidence.

  • 168. Cameli, Matteo
    et al.
    Righini, Francesca Maria
    Lisi, Matteo
    Bennati, Elena
    Navarri, Romina
    Lunghetti, Stefano
    Padeletti, Margherita
    Cameli, Paolo
    Tsioulpas, Charilaos
    Bernazzali, Sonia
    Maccherini, Massimo
    Sani, Guido
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Mondillo, Sergio
    Comparison of Right Versus Left Ventricular Strain Analysis as a Predictor of Outcome in Patients With Systolic Heart Failure Referred for Heart Transplantation2013In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 112, no 11, p. 1778-1784Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to explore the relation between right ventricular (RV) and left ventricular (LV) echocardiographic parameters with clinical outcome in patients with advanced heart failure referred for cardiac transplantation. Ninety-eight consecutive patients with advanced systolic heart failure, referred for cardiac transplant evaluation, were enrolled. All patients were prospectively followed for the development of new outcome events, which included hospitalization for acute heart failure, cardiovascular death, heart transplantation, intra-aortic balloon pump implantation, and ventricular assist device implantation. Conventional transthoracic echocardiography was performed in all subjects. RV longitudinal strain (RVLS) by speckle-tracking echocardiography was assessed by averaging all segments in apical 4-chamber view (global RVLS) and by averaging RV free-wall segments (free-wall RVLS). LV global longitudinal and global circumferential strains were also calculated. Of the 98 subjects at baseline, 46 had 67 new events during a mean follow-up of 1.5 +/- 0.9 years. Free-wall RVLS, global RVLS, N-terminal fragment of the prohormone brain natriuretic peptide, RV fractional area change, and LV end-diastolic volume were independently predictive of combined outcomes (all p<0.0001). The overall performance for the prediction of cardiovascular events was greatest for free-wall RVLS (area under the curve free-wall RVLS: 0.87; global RVLS: 0.67; RV fractional area change: 0.60; N-terminal fragment of the prohormone brain natriuretic peptide, 0.62; global circumferential strain: 0.55; global longitudinal strain: 0.35; and LV ejection fraction: 0.26). Free-wall RVLS showed the highest adjusted hazards ratio. A graded association between the grade of RV dysfunction and the risk of cardiovascular events was only evident for free-wall RVLS and global RVLS. In conclusion, in patients referred for heart transplantation, RVLS is a stronger predictor of outcome than LV longitudinal strain and other conventional parameters, providing a stronger prognostic stratification.

  • 169. Cameli, Matteo
    et al.
    Sciaccaluga, Carlotta
    Loiacono, Ferdinando
    Simova, Iana
    Miglioranza, Marcelo H.
    Nistor, Dan
    Bandera, Francesco
    Emdin, Michele
    Giannoni, Alberto
    Ciccone, Marco M.
    Devito, Fiorella
    Guaricci, Andrea Igoren
    Favale, Stefano
    Lisi, Matteo
    Mandoli, Giulia E.
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Mondillo, Sergio
    The analysis of left atrial function predicts the severity of functional impairment in chronic heart failure: The FLASH multicenter study2019In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 286, p. 87-91Article in journal (Refereed)
    Abstract [en]

    Background: Heart failure (HF) patients presentwith a variety of symptoms at different stages of the disease, but the underlying pathophysiology still is unclear. Left atrial (LA) function might be tightly related to changes in patients' symptoms, more than morphological and anatomic heart features, measurable by ultrasound imaging technique. This study sought to investigate the correlation between LA function, assessed by Speckle Tracking Echocardiography (STE) and Quality of Life (QoL), assessed by theMinnesota Livingwith Heart Failure Questionnaire (MLHFQ), in patients with chronic HF. Methods: Clinically stable HF outpatients (n = 369) were enrolled from 7 different international centres and underwent echocardiographic studies. Patients >75 years old and with atrial fibrillation were excluded. LA strain during reservoir phase (LASr) by STE was measured in all subjects by averaging the 6 atrial segments. LA size was assessed using biplane volume and 4-chamber area acquisition. Results: LASr strongly correlated with both MLHFQ total score (r = -0.87; p < 0.0001). Less significant correlations between MLHFQ and either LA volume or left ventricular global longitudinal strain (LV-GLS) were found (r = 0.28; p = 0.05 and r = 0.30; p = 0.01, respectively). No significant correlation was found between MLHFQ score, LVEF (r = -0.15; p = ns), E/E' ratio (r = 0.19; p = ns), and E/A ratio (r = 0.20; p = ns). Among all echocardiographic parameters analyzed, LASr presented the highest diagnostic accuracy (AUC = 0.74) in predicting a poor QoL (>45), when compared with LV-GLS (AUC = 0.61), LA volume (AUC = 0.54) and E/e' ratio (AUC = 0.51). Conclusions: In patients with HF, irrespective of etiology, LA function strongly correlates with patients' QoL. (C) 2019 Elsevier B.V. All rights reserved.

  • 170.
    Cameli, Matteo
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Sparla, S.
    Fineschi, M.
    Favilli, R.
    Pierli, C.
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Mondillo, S.
    Left atrial strain as independent parameter to predict left ventricular end diastolic pressure2014In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, no Supplement 1, Meeting abstract P1531, p. 278-279Article in journal (Other academic)
  • 171. Camen, S.
    et al.
    Ojeda, F. M.
    Niiranen, T.
    Gianfagna, F.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lochen, M. L.
    Kee, F.
    Blankenberg, S.
    Jørgensen, T.
    Zeller, T.
    Kuulasmaa, K.
    Linneberg, A.
    Salomaa, V.
    Iacoviello, L.
    Schnabel, R.
    Temporal relations between atrial fibrillation and ischemic stroke and their prognostic impact on mortality2018In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 39, p. 204-205Article in journal (Other academic)
    Abstract [en]

    Introduction: Atrial fibrillation (AF) and stroke are common diseases and AF is a well-established risk factor for stroke. The physiological mechanism of atrial dysfunction, disturbed hemodynamics and arterial thromboembolism links the pathologies. However, limited evidence is available on the temporal relationship between stroke and AF and the impact of subsequent disease onset on mortality in the community.

    Methods and results: Across five prospective community cohorts (DanMONICA, FINRISK, Moli-Sani project, Northern Sweden MONICA study, The Tromsø Study) of the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE)-project we assessed baseline cardiovascular risk factors in 101164 individuals, median age 46.1 (25th, 75th percentile 35.8, 57.6) years, 48.4% men. We followed them for incident stroke and AF and determined the relation of subsequent disease diagnosis with overall mortality. Follow-up (FU) for stroke and AF was based upon linkage with national hospitalization registries or administrative registries for ambulatory visits to specialized hospitals.

    Over a median FU of 16.1 years N=4556 individuals were diagnosed solely with AF, N=2269 had a stroke but no AF diagnosed, and N=898 developed both stroke and AF during FU. Participants who developed either AF or stroke as the index event revealed a similar baseline risk factor profile. Temporal relations showed a peak of the diagnosis of both diseases within the years around the diagnosis of the other disease. The highest incidence rates of stroke were observed within a five-year interval prior to AF diagnosis. Cox regression showed an association of baseline stroke with diagnosis of AF during FU (hazard ratio (HR) 1.29; 95% confidence interval (CI) 1.11–1.50; p<0.001).

    In multivariable-adjusted Cox regression analyses with time-dependent covariates excluding individuals with diagnosis of both AF and stroke or death within 30 days, subsequent diagnosis of AF after stroke was associated with a higher overall mortality (HR, 3.51; 95% CI 1.87–6.59; p<0.001); subsequent stroke after the diagnosis of AF was associated with a HR of 2.39 (95% CI 1.59–3.60; p<0.001).

    Conclusions: Stroke and AF are common comorbidities in older adults with an overlapping risk factor profile. The temporal relations appear to be bidirectional, although uncertainty regarding disease onset remains due to the often paroxysmal and asymptomatic nature of AF. Stroke may precede detection of AF by years. The subsequent diagnosis of both diseases significantly increases mortality risk. Whether targeting modifiable risk factors or improved screening for AF after stroke would improve survival needs to be determined.

  • 172. Cameron, A. J.
    et al.
    Magliano, D. J.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    A systematic review of the impact of including both waist and hip circumference in risk models for cardiovascular diseases, diabetes and mortality2013In: Obesity Reviews, ISSN 1467-7881, E-ISSN 1467-789X, Vol. 14, no 1, p. 86-94Article, review/survey (Refereed)
    Abstract [en]

    Both a larger waist and narrow hips are associated with heightened risk of diabetes, cardiovascular diseases and premature mortality. We review the risk of these outcomes for levels of waist and hip circumferences when terms for both anthropometric measures were included in regression models. MEDLINE and EMBASE were searched (last updated July 2012) for studies reporting the association with the outcomes mentioned earlier for both waist and hip circumferences (unadjusted and with both terms included in the model). Ten studies reported the association between hip circumference and death and/or disease outcomes both unadjusted and adjusted for waist circumference. Five studies reported the risk associated with waist circumference both unadjusted and adjusted for hip circumference. With the exception of one study of venous thromboembolism, the full strength of the association between either waist circumference or hip circumference with morbidity and/or mortality was only apparent when terms for both anthropometric measures were included in regression models. Without accounting for the protective effect of hip circumference, the effect of obesity on risk of death and disease may be seriously underestimated. Considered together (but not as a ratio measure), waist and hip circumference may improve risk prediction models for cardiovascular disease and other outcomes.

  • 173.
    Camilla, Sandberg
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Pomeroy, Jeremy
    Thilén, Ulf
    Gradmark, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Wadell, Karin
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Habitual Physical Activity in Adults with Congenital Heart Disease Compared with Age- and Sex- Matched Controls2016In: Canadian Journal of Cardiology, ISSN 0828-282X, E-ISSN 1916-7075, Vol. 32, no 4, p. 547-553Article in journal (Refereed)
    Abstract [en]

    Background: Most adult patients with congenital heart disease (CHD) have reduced aerobic exercise capacity. Their habitual physical activity (PA) level is, however, less well studied. In this study habitual PA level in a cohort of adults with CHD compared to healthy age and gender matched controls was investigated.

    Methods: Eighty adults with CHD, classed as either “complex” (n=40) or “simple” (n=40), and 42 healthy controls were studied with a combined uniaxial accelerometer and heart rate monitor worn during 4 consecutive days. We analysed 1) the time spent during ≥ moderate/vigorous PA, 2) accelerometer counts/day and 3) to what extent the World Health Organization recommendations on PA were reached.

    Results: Patients with simple lesions had higher total accelerometer counts/day compared to both patients with complex lesions and controls (simple lesions; median (IQR) 107.7(63.4) vs. complex lesions; 72.8(53.5) and controls; 78.3(49.6), p≤0.001 and p=0.002). Furthermore, no differences in time spent during ≥ moderate-to-vigorous PA was found between patients and controls. In addition 46% of the patients with simple lesions, 55% of the patients with complex lesions and 44% of the controls did not reach the W.H.O.-recommended level of daily PA, but no significant differences between groups were found. There were no differences in achieving recommended PA level between patients in NYHA I vs. NYHA II+III.

    Conclusions: Patients with CHD follow the same PA-level pattern as the general population. Broad strategies promoting an active lifestyle are needed across the population and especially for patients with complex CHD and impaired NYHA class.

  • 174.
    Carlberg, B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Blood Pressure in Acute Stroke: Causes and consequences1994In: Hypertension Research, ISSN 0916-9636, E-ISSN 1348-4214, Vol. 17, no Suppl I, p. S77-S82Article in journal (Other academic)
  • 175.
    Carlberg, B
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Asplund, Kjell
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hägg, E
    Course of blood pressure in different subsets of patients after acute stroke1991In: Cerebrovascular Diseases, ISSN 1015-9770, E-ISSN 1421-9786, Vol. 1, p. 281-287Article in journal (Refereed)
  • 176.
    Carlberg, B
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Asplund, Kjell
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hägg, E
    Factors influencing admission blood pressure levels in patients with acute stroke.1991In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 22, no 4, p. 527-30Article in journal (Refereed)
    Abstract [en]

    In clinical practice, patients with acute stroke often have high blood pressure. The aim of this study was to investigate factors correlated with blood pressure elevation in 843 consecutive stroke patients on hospital admission to a nonintensive stroke unit. Using a multivariate analysis model, we analyzed the influence on admission blood pressure of sex, age, previous hypertension, cardiac failure, diabetes, type of stroke, impaired consciousness, and latency between onset of symptoms and admission. Previous hypertension was the strongest predictor (p less than 0.001) of elevated blood pressure on admission, followed by the presence of intracerebral hemorrhage (p less than 0.001). The latency between onset of symptoms and admission showed no correlation with blood pressure levels at hospitalization. Previously, high blood pressure levels on hospital admission have been shown to decline within a few days in hospital. We therefore hypothesize that mental stress on hospital admission may be a major factor in the blood pressure elevation seen in acute stroke.

  • 177.
    Carlberg, B
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Asplund, Kjell
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hägg, E
    High blood pressure in acute stroke--is it white coat hypertension?1990In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 228, no 3, p. 291-2Article in journal (Refereed)
  • 178.
    Carlberg, B
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Asplund, Kjell
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hägg, E
    The prognostic value of admission blood pressure in patients with acute stroke.1993In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 24, no 9, p. 1372-5Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Patients with acute stroke are often found to have high blood pressures at hospital admission. Previous studies have shown variable results regarding the prognostic value of high blood pressure in acute stroke. The aim of this study was to investigate the prognostic value of admission blood pressure in a population-based sample of patients with acute stroke.

    METHODS: Eighty-five patients with intracerebral hemorrhage and 831 with ischemic disease were included in the study. The relations between admission blood pressure and 30-day mortality were studied by logistic regression analyses.

    RESULTS: High blood pressure in patients with impaired consciousness on hospital admission was significantly related to 30-day mortality in patients with intracerebral hemorrhage (P = .037) and in patients with ischemic disease (P < .0001). In patients without impaired consciousness, high blood pressure at time of admission was not related to increased mortality at 30 days.

    CONCLUSIONS: High admission blood pressure in alert stroke patients was not related to increased mortality. Stroke patients with impaired consciousness showed higher mortality rates with increasing blood pressure. However, this does not provide a basis for recommending antihypertensive therapy for such patients.

  • 179.
    Carlberg, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    The challenge of preventing dementia by antihypertensive treatment2013In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 31, no 9, p. 1780-1781Article in journal (Other academic)
  • 180.
    Carlberg, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    What do we know about the risks of stopping antihypertensive treatment?2014In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 32, no 7, p. 1400-1401Article in journal (Other academic)
  • 181. Carlsson, Axel C.
    et al.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Ruge, Toralph
    Larsson, Anders
    Arnlov, Johan
    Levels of soluble tumor necrosis factor receptor 1 and 2, gender, and risk of myocardial infarction in Northern Sweden2018In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 272, p. 41-46Article in journal (Refereed)
    Abstract [en]

    Background and aims: Soluble receptors for tumor necrosis factor alpha (sTNFR1 and sTNFR2) have been associated with cardiovascular diseases, and some evidence points towards a difference in associated risk between men and women. We aimed to study the association between sTNFR1 and sTNFR2 and incident myocardial infarctions (MI) and to explore the influence of established cardiovascular risk factors in men and women.& para;& para;Methods: We conducted a nested case control study in three large Swedish cohorts, including 533 myocardial infarction cases, and 1003 age-, sex- and cohort-matched controls. Odds ratios (OR) with 95% confidence intervals (CI) were calculated.& para;& para;Results: An association between circulating sTNFR1 and sTNFR2 and an increased risk for MI was found when comparing cases and controls. The odds ratios were significant after adjustment for established cardiovascular risk factors and C-reactive protein in women (OR 1.44, 95% CI 1.08-1.93 for TNFR1, and 1.61, 95% CI 1.11-2.34 for TNFR2), but was abolished in men. Women with a combination of elevated CRP and values in the upper quartile of TNFR1 or TNFR2 had a 5-fold higher risk of myocardial infarction versus those with normal CRP and values in the lower three quartiles of TNFR1 or TNFR2.& para;& para;Conclusions: As the risk estimates for TNFR1 and TNFR2 were higher and remained significant after adjustments for established cardiovascular risk factors in women but not in men, a potential role for TNFR1 and TNFR2 in identifying women with a higher MI risk is possible. The future clinical role of TNFR1 and TNFR2 in combination with CRP to identify high risk patients for coronary heart disease has yet to be determined. 

  • 182. Carlsson, Axel C.
    et al.
    Ruge, Toralph
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Sundstrom, Johan
    Ingelsson, Erik
    Larsson, Anders
    Lind, Lars
    Arnlov, Johan
    Association Between Circulating Endostatin, Hypertension Duration, and Hypertensive Target-Organ Damage2013In: Hypertension, ISSN 0194-911X, E-ISSN 1524-4563, Vol. 62, no 6, p. 1146-1151Article in journal (Refereed)
    Abstract [en]

    Our aim is to study associations between circulating endostatin, hypertension duration, and hypertensive target-organ damage. Long-term hypertension induces cardiovascular and renal remodeling. Circulating endostatin, a biologically active derivate of collagen XVIII, has been suggested to be a relevant marker for extracellular matrix turnover and remodeling in various diseases. However, the role of endostatin in hypertension and hypertensive target-organ damage is unclear. Serum endostatin was measured in 2 independent community-based cohorts: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; women 51%; n=812; mean age, 75 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n=785; mean age, 77.6 years). Retrospective data on blood pressure measurements and antihypertensive medication (PIVUS >5 years, ULSAM >27 years), and cross-sectional data on echocardiographic left ventricular mass, endothelial function (endothelium-dependent vasodilation assessed by the invasive forearm model), and urinary albumin/creatinine ratio were available. In PIVUS, participants with 5 years of history of hypertension portrayed 0.42 SD (95% confidence interval, 0.23-0.61; P<0.001) higher serum endostatin, compared with that of normotensives. This association was replicated in ULSAM, in which participants with 27 years hypertension duration had the highest endostatin (0.57 SD higher; 95% confidence interval, 0.35-0.80; P<0.001). In addition, higher endostatin was associated with higher left ventricular mass, worsened endothelial function, and higher urinary albumin/creatinine ratio (P<0.03 for all) in participants with prevalent hypertension. Circulating endostatin is associated with the duration of hypertension, and vascular, myocardial, and renal indices of hypertensive target-organ damage. Further studies are warranted to assess the prognostic role of endostatin in individuals with hypertension.

  • 183. Carrasquilla, German D.
    et al.
    Chiavenna, Chiara
    Bottai, Matteo
    Magnusson, Patrik K.
    Santacatterina, Michele
    Wolk, Alicja
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Engstrom, Gunnar
    Borgfeldt, Christer
    Pedersen, Nancy L.
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Berglund, Anita
    Leander, Karin
    The association between menopausal hormone therapy and coronary heart disease depends on timing of initiation in relation to menopause onset. Results based on pooled individual participant data from The Combined Cohorts of Menopausal Women - Studies of Register Based Health Outcomes in Relation to Hormonal Drugs (COMPREHEND) study2015In: Menopause: The Journal of the North American Menopause, ISSN 1072-3714, E-ISSN 1530-0374, Vol. 22, no 12, p. 1373-1373Article in journal (Other academic)
  • 184. Carrasquilla, German D.
    et al.
    Frumento, Paolo
    Berglund, Anita
    Borgfeldt, Christer
    Bottai, Matteo
    Chiavenna, Chiara
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Engström, Gunnar
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Magnusson, Patrik K.
    Nilsson, Peter M.
    Pedersen, Nancy L.
    Wolk, Alicja
    Leander, Karin
    Postmenopausal hormone therapy and risk of stroke: A pooled analysis of data from population-based cohort studies2017In: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 14, no 11, article id e1002445Article in journal (Refereed)
    Abstract [en]

    Background: Recent research indicates a favourable influence of postmenopausal hormone therapy (HT) if initiated early, but not late, on subclinical atherosclerosis. However, the clinical relevance of timing of HT initiation for hard end points such as stroke remains to be determined. Further, no previous research has considered the timing of initiation of HT in relation to haemorrhagic stroke risk. The importance of the route of administration, type, active ingredient, and duration of HT for stroke risk is also unclear. We aimed to assess the association between HT and risk of stroke, considering the timing of initiation, route of administration, type, active ingredient, and duration of HT.

    Methods and findings: Data on HT use reported by the participants in 5 population-based Swedish cohort studies, with baseline investigations performed during the period 1987-2002, were combined in this observational study. In total, 88,914 postmenopausal women who reported data on HT use and had no previous cardiovascular disease diagnosis were included. Incident events of stroke (ischaemic, haemorrhagic, or unspecified) and haemorrhagic stroke were identified from national population registers. Laplace regression was employed to assess crude and multivariable-adjusted associations between HT and stroke risk by estimating percentile differences (PDs) with 95% confidence intervals (CIs). The fifth and first PDs were calculated for stroke and haemorrhagic stroke, respectively. Crude models were adjusted for age at baseline only. The final adjusted models included age at baseline, level of education, smoking status, body mass index, level of physical activity, and age at menopause onset. Additional variables evaluated for potential confounding were type of menopause, parity, use of oral contraceptives, alcohol consumption, hypertension, dyslipidaemia, diabetes, family history of cardiovascular disease, and cohort. During a median follow-up of 14.3 years, 6,371 first-time stroke events were recorded; of these, 1,080 were haemorrhagic. Following multivariable adjustment, early initiation (<5 years since menopause onset) of HT was associated with a longer stroke-free period than never use (fifth PD, 1.00 years; 95% CI 0.42 to 1.57), but there was no significant extension to the time period free of haemorrhagic stroke (first PD, 1.52 years; 95% CI -0.32 to 3.37). When considering timing as a continuous variable, the stroke-free and the haemorrhagic stroke-free periods were maximal if HT was initiated approximately 0-5 years from the onset of menopause. If single conjugated equine oestrogen HT was used, late initiation of HT was associated with a shorter stroke-free (fifth PD, -4.41 years; 95% CI -7.14 to -1.68) and haemorrhagic stroke-free (first PD, -9.51 years; 95% CI -12.77 to -6.24) period than never use. Combined HT when initiated late was significantly associated with a shorter haemorrhagic stroke-free period (first PD, -1.97 years; 95% CI -3.81 to -0.13), but not with a shorter stroke-free period (fifth PD, -1.21 years; 95% CI -3.11 to 0.68) than never use. Given the observational nature of this study, the possibility of uncontrolled confounding cannot be excluded. Further, immortal time bias, also related to the observational design, cannot be ruled out.

    Conclusions: When initiated early in relation to menopause onset, HT was not associated with increased risk of incident stroke, regardless of the route of administration, type of HT, active ingredient, and duration. Generally, these findings held also for haemorrhagic stroke. Our results suggest that the initiation of HT 0-5 years after menopause onset, as compared to never use, is associated with a decreased risk of stroke and haemorrhagic stroke. Late initiation was associated with elevated risks of stroke and haemorrhagic stroke when conjugated equine oestrogen was used as single therapy. Late initiation of combined HT was associated with haemorrhagic stroke risk.

  • 185. Caruana, Maryanne
    et al.
    Apers, Silke
    Kovacs, Adrienne H.
    Luyckx, Koen
    Thomet, Corina
    Budts, Werner
    Sluman, Maayke
    Eriksen, Katrine
    Dellborg, Mikael
    Berghammer, Malin
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Soufi, Alexandra
    Callus, Edward
    Moons, Philip
    Grech, Victor
    Red Flags for Maltese Adults with Congenital Heart Disease: Poorer Dental Care and Less Sports Participation Compared to Other European Patients-An APPROACH-IS Substudy2017In: Pediatric Cardiology, ISSN 0172-0643, E-ISSN 1432-1971, Vol. 38, no 5, p. 965-973Article in journal (Refereed)
    Abstract [en]

    Studies in recent years have explored lifestyle habits and health-risk behaviours in adult congenital heart disease (ACHD) patients when compared to controls. The aim of this study was to investigate differences in lifestyle habits between Maltese and other European ACHD patients. Data on alcohol consumption, cigarette smoking, substance misuse, dental care and physical activity collected in 2013-2015 during "Assessment of Patterns of Patient-Reported Outcomes in Adults with Congenital Heart disease-International Study" (APPROACH-IS) were analysed. Responses from 119 Maltese participants were compared to those of 1616 participants from Belgium, France, Italy, Norway, Sweden, Switzerland and the Netherlands. Significantly fewer Maltese patients with simple (Maltese 84.1% vs. European 97.5%, p < 0.001) and moderately complex CHD (Maltese 83.6% vs. European 97.4%, p < 0.001) brushed their teeth daily. Only 67.2% of Maltese with moderately complex disease had dental reviews in the previous year compared to 80.3% of Europeans (p = 0.02). Maltese patients with simple (Maltese 31.8% vs. European 56.1%, p = 0.002) and moderately complex lesions (Maltese 30.0% vs. European 59.2%, p < 0.001) performed less regular sport activities. Comparison by country showed Maltese patients to have significantly poorer tooth brushing and sports participation than patients from any other participating country. Alcohol consumption, cigarette smoking and substance misuse were not significantly different. This study highlights lifestyle aspects that Maltese ACHD patients need to improve on, which might not be evident upon comparing patients to non-CHD controls. These findings should also caution researchers against considering behaviours among patients in one country as necessarily representative of patients on the larger scale.

  • 186. Chang, Chuchun L.
    et al.
    Garcia-Arcos, Itsaso
    Nyrén, Rakel
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Olivecrona, Gunilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Kim, Ji Young
    Hu, Yunying
    Agrawal, Rishi R.
    Murphy, Andrew J.
    Goldberg, Ira J.
    Deckelbaum, Richard J.
    Lipoprotein Lipase Deficiency Impairs Bone Marrow Myelopoiesis and Reduces Circulating Monocyte Levels2018In: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 38, no 3, p. 509-519Article in journal (Refereed)
    Abstract [en]

    Objective: Tissue macrophages induce and perpetuate proinflammatory responses, thereby promoting metabolic and cardiovascular disease. Lipoprotein lipase (LpL), the rate-limiting enzyme in blood triglyceride catabolism, is expressed by macrophages in atherosclerotic plaques. We questioned whether LpL, which is also expressed in the bone marrow (BM), affects circulating white blood cells and BM proliferation and modulates macrophage retention within the artery.

    Approach and Results: We characterized blood and tissue leukocytes and inflammatory molecules in transgenic LpL knockout mice rescued from lethal hypertriglyceridemia within 18 hours of life by muscle-specific LpL expression (MCKL0 mice). LpL-deficient mice had ≈40% reduction in blood white blood cell, neutrophils, and total and inflammatory monocytes (Ly6C/Ghi). LpL deficiency also significantly decreased expression of BM macrophage-associated markers (F4/80 and TNF-α [tumor necrosis factor α]), master transcription factors (PU.1 and C/EBPα), and colony-stimulating factors (CSFs) and their receptors, which are required for monocyte and monocyte precursor proliferation and differentiation. As a result, differentiation of macrophages from BM-derived monocyte progenitors and monocytes was decreased in MCKL0 mice. Furthermore, although LpL deficiency was associated with reduced BM uptake and accumulation of triglyceride-rich particles and macrophage CSF–macrophage CSF receptor binding, triglyceride lipolysis products (eg, linoleic acid) stimulated expression of macrophage CSF and macrophage CSF receptor in BM-derived macrophage precursor cells. Arterial macrophage numbers decreased after heparin-mediated LpL cell dissociation and by genetic knockout of arterial LpL. Reconstitution of LpL-expressing BM replenished aortic macrophage density.

    Conclusions: LpL regulates peripheral leukocyte levels and affects BM monocyte progenitor differentiation and aortic macrophage accumulation.

  • 187.
    Charisopoulou, Dafni
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Department of Paediatric Cardiology, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
    Koulaouzidis, George
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Department of Cardiology, Mid Yorkshire Hospitals NHS Trust, Wakefield, UK.
    Rydberg, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Molecular and Clinical Sciences Research Institute, St George University London, London, UK; Brunel University, Middlesex, UK.
    Exercise worsening of electromechanical disturbances: a predictor of arrhythmia in long QT syndrome2019In: Clinical Cardiology, ISSN 0160-9289, E-ISSN 1932-8737, Vol. 42, no 2, p. 235-240Article in journal (Refereed)
    Abstract [en]

    Background; Electromechanical (EM) coupling heterogeneity is significant in long QT syndrome (LQTS), particularly in symptomatic patients; EM window (EMW) has been proposed as an indicator of interaction and a better predictor of arrhythmia than QTc. Hypothesis To investigate the dynamic response of EMW to exercise in LQTS and its predictive value of arrhythmia.

    Methods: Forty-seven LQTS carriers (45 +/- 15 years, 20 with arrhythmic events), and 35 controls underwent exercise echocardiogram. EMW was measured as the time difference between aortic valve closure on Doppler and the end of QT interval on the superimposed electrocardiogram (ECG). Measurements were obtained at rest, peak exercise (PE) and 4 minutes into recovery.

    Results: Patients did not differ in age, gender, heart rate, or left ventricular ejection fraction but had a negative resting EMW compared with controls (-42 +/- 22 vs 17 +/- 5 ms, P < 0.0001). EMW became more negative at PE (-89 +/- 43 vs 16 +/- 7 ms, P = 0.0001) and recovery (-65 +/- 39 vs 16 +/- 6 ms, P = 0.001) in patients, particularly the symptomatic, but remained unchanged in controls. PE EMW was a stronger predictor of arrhythmic events than QTc (AUC:0.765 vs 0.569, P < 0.001). B-blockers did not affect EMW at rest but was less negative at PE (BB: -66 +/- 21 vs no-BB: -113 +/- 25 ms, P < 0.001). LQT1 patients had worse PE EMW negativity than LQT2.

    Conclusion: LQTS patients have significantly negative EMW, which worsens with exercise. These changes are more pronounced in patients with documented arrhythmic events and decrease with B-blocker therapy. Thus, EMW assessment during exercise may help improve risk stratification and management of LQTS patients.

  • 188. Chatziioannou, Aristotelis
    et al.
    Georgiadis, Panagiotis
    Hebels, Dennie G
    Liampa, Irene
    Valavanis, Ioannis
    Bergdahl, Ingvar A
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Palli, Domenico
    Chadeau-Hyam, Marc
    Siskos, Alexandros P
    Keun, Hector
    Botsivali, Maria
    de Kok, Theo M C M
    Pérez, Almudena Espín
    Kleinjans, Jos C S
    Vineis, Paolo
    Kyrtopoulos, Soterios A
    Blood-based omic profiling supports female susceptibility to tobacco smoke-induced cardiovascular diseases2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 42870Article in journal (Refereed)
    Abstract [en]

    We recently reported that differential gene expression and DNA methylation profiles in blood leukocytes of apparently healthy smokers predicts with remarkable efficiency diseases and conditions known to be causally associated with smoking, suggesting that blood-based omic profiling of human populations may be useful for linking environmental exposures to potential health effects. Here we report on the sex-specific effects of tobacco smoking on transcriptomic and epigenetic features derived from genome-wide profiling in white blood cells, identifying 26 expression probes and 92 CpG sites, almost all of which are affected only in female smokers. Strikingly, these features relate to numerous genes with a key role in the pathogenesis of cardiovascular disease, especially thrombin signaling, including the thrombin receptors on platelets F2R (coagulation factor II (thrombin) receptor; PAR1) and GP5 (glycoprotein 5), as well as HMOX1 (haem oxygenase 1) and BCL2L1 (BCL2-like 1) which are involved in protection against oxidative stress and apoptosis, respectively. These results are in concordance with epidemiological evidence of higher female susceptibility to tobacco-induced cardiovascular disease and underline the potential of blood-based omic profiling in hazard and risk assessment.

  • 189. Chockalingam, Priya
    et al.
    Crotti, Lia
    Girardengo, Giulia
    Johnson, Jonathan N
    Harris, Katy M
    van der Heijden, Jeroen F
    Hauer, Richard NW
    Beckmann, Britt M
    Spazzolini, Carla
    Rordorf, Roberto
    Rydberg, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Clur, Sally-Ann B
    Fischer, Markus
    van den Heuvel, Freek
    Kaeaeb, Stefan
    Blom, Nico A
    Ackerman, Michael J
    Schwartz, Peter J
    Wilde, Arthur AM
    Not all beta-blockers are equal in the management of Long QT Syndrome types 1 and 2: higher recurrence of events under metoprolol2012In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 60, no 20, p. 2092-2099Article in journal (Refereed)
    Abstract [en]

    Objectives The purpose of this study was to compare the efficacy of beta-blockers in congenital long QT syndrome (LQTS). Background Beta-blockers are the mainstay in managing LQTS. Studies comparing the efficacy of commonly used beta-blockers are lacking, and clinicians generally assume they are equally effective.

    Methods Electrocardiographic and clinical parameters of 382 LQT1/LQT2 patients initiated on propranolol (n = 134), metoprolol (n = 147), and nadolol (n = 101) were analyzed, excluding patients <1 year of age at beta-blocker initiation. Symptoms before therapy and the first breakthrough cardiac events (BCEs) were documented.

    Results Patients (56% female, 27% symptomatic, heart rate 76 +/- 16 beats/min, QTc 472 +/- 46 ms) were started on beta-blocker therapy at a median age of 14 years (interquartile range: 8 to 32 years). The QTc shortening with propranolol was significantly greater than with other beta-blockers in the total cohort and in the subset with QTc >480 ms. None of the asymptomatic patients had BCEs. Among symptomatic patients (n = 101), 15 had BCEs (all syncopes). The QTc shortening was significantly less pronounced among patients with BCEs. There was a greater risk of BCEs for symptomatic patients initiated on metoprolol compared to users of the other 2 beta-blockers combined, after adjustment for genotype (odds ratio: 3.95, 95% confidence interval: 1.2 to 13.1, p = 0.025). Kaplan-Meier analysis showed a significantly lower event-free survival for symptomatic patients receiving metoprolol compared to propranolol/nadolol.

    Conclusions Propranolol has a significantly better QTc shortening effect compared to metoprolol and nadolol, especially in patients with prolonged QTc. Propranolol and nadolol are equally effective, whereas symptomatic patients started on metoprolol are at a significantly higher risk for BCEs. Metoprolol should not be used for symptomatic LQT1 and LQT2 patients.

    (J Am Coll Cardiol 2012;60:2092-9) (C) 2012 by the American College of Cardiology Foundation

  • 190. Cicala, Silvana
    et al.
    de Simone, Giovanni
    Wachtell, Kristian
    Gerdts, Eva
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nieminen, Markku S
    Dahlöf, Björn
    Devereux, Richard B
    Clinical impact of 'in-treatment' wall motion abnormalities in hypertensive patients with left ventricular hypertrophy: the LIFE study2008In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 26, no 4, p. 806-812Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Left ventricular systolic wall motion abnormalities have prognostic value. Whether wall motion detected by serial echocardiographic examinations predicts prognosis in hypertensive patients with left ventricular hypertrophy (LVH) without clinically recognized atherosclerotic disease has, however, never been investigated. We examined whether 'in-treatment' wall motion abnormalities predicted outcome in the Losartan Intervention For Endpoint (LIFE) reduction in hypertension echocardiographic substudy.

    METHODS: We studied 749 patients without coronary artery disease, myocardial infarction (MI), or stroke history. Echocardiographic segmental wall motion abnormalities at baseline and annual re-evaluations ('as time-varying covariate') were examined in relation to endpoints (cardiovascular mortality, MI, stroke, and hospitalized heart failure). Adjusted Cox regression was used to analyze the primary composite endpoint of cardiovascular death, MI, or stroke and, separately, for fatal and nonfatal MI and hospitalized heart failure.

    RESULTS: During a mean follow-up of 4.8 years, an event was recorded in 67 (9%) patients. In Cox models after adjusting for age, gender, treatment, blood pressure lowering, and serial change of left ventricular mass index, 'in-treatment' segmental wall motion abnormalities were associated with subsequent composite endpoint [hazard ratio = 2.1, 95% confidence interval (CI) 1.1-3.8; P = 0.019] and MI [hazard ratio = 3.7 (1.5-8.9); P = 0.004].

    CONCLUSION: In hypertensive patients with LVH and no history of cardiovascular disease, 'in-treatment' left ventricular wall motion abnormalities are associated with increased likelihood of subsequent cardiovascular events independent of age, gender, blood pressure lowering, treatment modality, and in-treatment left ventricular mass index.

  • 191. Cramariuc, Dana
    et al.
    Rogge, Barbara Patricia
    Lønnebakken, Mai Tone
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Bahlmann, Edda
    Gohlke-Bärwolf, Christa
    Chambers, John B
    Pedersen, Terje R
    Gerdts, Eva
    Sex differences in cardiovascular outcome during progression of aortic valve stenosis2015In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 101, no 3, p. 209-214Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Women with severe aortic valve stenosis (AS) have better LV systolic function and more concentric LV geometry than their male counterparts. However, sex differences in cardiovascular (CV) outcome during progression of AS have not been reported from a longitudinal prospective study.

    METHODS: Doppler echocardiography and CV events were recorded during a median of 4.0 years in 979 men and 632 women aged 28-86 (mean 67±10) years in the Simvastatin Ezetimibe in Aortic Stenosis (SEAS) study. LV systolic function was assessed by EF and midwall shortening (MWS). Study outcomes were AS-related events, ischaemic CV events and total mortality.

    RESULTS: The annular cumulative incidence of AS events, ischaemic CV events and death was 8.1%, 3.4% and 2.8% in women, and 8.9%, 4.4% and 2.4% in men, respectively. Women and men had similar AS progression rate whether measured by peak jet velocity, mean gradient or valve area. In multivariate analyses, female sex independently predicted less reduction in LV MWS and EF during follow-up (both p<0.05). In time-varying Cox analyses, women had a 40% lower rate of ischaemic CV events (95% CI 21% to 54%), in particular, more than 50% lower rate of stroke and coronary artery bypass grafting, and a 31% lower all-cause mortality (95% CI 1% to 51%), independent of active study treatment, age and hypertension, as well as time-varying valve area, low systolic function and abnormal LV geometry. AS event rate did not differ by sex.

    CONCLUSIONS: In the SEAS study, women and men had similar rates of AS progression and AS-related events. However, women had lower total mortality and ischaemic CV event rate than men independent of confounders.

    TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT00092677.

  • 192. Crowe, F. L.
    et al.
    Key, T. J.
    Appleby, P. N.
    Overvad, K.
    Schmidt, E. B.
    Egeberg, R.
    Tjonneland, A.
    Kaaks, R.
    Teucher, B.
    Boeing, H.
    Weikert, C.
    Trichopoulou, A.
    Ouranos, V.
    Valanou, E.
    Masala, G.
    Sieri, S.
    Panico, S.
    Tumino, R.
    Matullo, G.
    Bueno-de-Mesquita, H. B.
    Boer, J. M. A.
    Beulens, J. W. J.
    van der Schouw, Y. T.
    Quiros, J. R.
    Buckland, G.
    Sanchez, M-J
    Dorronsoro, M.
    Huerta, J. M.
    Moreno-Iribas, C.
    Hedblad, B.
    Jansson, J. H.
    Wennberg, Patrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Khaw, K-T
    Wareham, N.
    Ferrari, P.
    Illner, A-K
    Chuang, S-C
    Norat, T.
    Danesh, J.
    Riboli, E.
    Dietary fibre intake and ischaemic heart disease mortality: the European Prospective Investigation into Cancer and Nutrition-Heart study2012In: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 66, no 8, p. 950-956Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/OBJECTIVES: Evidence from prospective studies is consistent in showing an inverse association between dietary fibre intake and risk of ischaemic heart disease (IHD), but whether dietary fibre from various food sources differ in their effect on IHD risk is less clear. The objective of this study was to assess the associations of total and food sources of dietary fibre with IHD mortality in the European Prospective Investigation into Cancer and Nutrition-Heart study. SUBJECTS/METHODS: Participants were 306 331 men and women from eight European countries. Dietary fibre intake was assessed using centre or country-specific diet questionnaires and calibrated using a 24-h diet recall. RESULTS: After an average follow-up of 11.5 years, there were 2381 IHD deaths among participants without cardiovascular disease at baseline. The calibrated intake of dietary fibre was inversely related with IHD mortality; each 10 g/day was associated with a 15% lower risk (relative risk (RR) 0.85; 95% confidence interval (CI): 0.73-0.99, P = 0.031). There was no difference in the associations of the individual food sources of dietary fibre with the risk of IHD mortality; RR for each 5 g/day higher cereal fibre intake was 0.91 (CI: 0.82-1.01), RR for each 2.5 g/day fruit fibre intake was 0.94 (CI: 0.88-1.01) and RR for each 2.5 g/day vegetable fibre intake was 0.90 (95% CI: 0.76-1.07). CONCLUSION: A higher consumption of dietary fibre is associated with a lower risk of fatal IHD with no clear difference in the association with IHD for fibre from cereals, fruits or vegetables.

  • 193. Csengeri, D.
    et al.
    Spruenker, N. A.
    Di Castelnuovo, A.
    Niiranen, T.
    Söderberg, Stefan
    Umeå University Hospital.
    Magnussen, C.
    Lochen, M. J.
    Kee, F.
    Blankenberg, S.
    Jørgensen, T.
    Kuulasmaa, K.
    Zeller, T.
    Salomaa, V.
    Iacoviello, L.
    Schnabel, R.
    Alcohol consumption and risk of atrial fibrillation - results from the BiomarCaRE Consortium2018In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 39, p. 902-903Article in journal (Other academic)
    Abstract [en]

    Background: Atrial fibrillation (AF) is an arrhythmia with high impact on public health. Among modifiable risk factors for the disease the role of alcohol consumption (AC) has remained inconsistent.

    Purpose: To assess the association between AC and incident AF across European cohorts.

    Methods: To study the association between self-reported AC and incident AF in N=107,845 community-based individuals from the BiomarCaRE consortium, 106,915 individuals free of AF at baseline were followed up for AF and stroke after AF. We assessed AC using validated questionnaires. Biomarkers N-terminal pro B-type natriuretic peptide (Nt-proBNP) and high sensitivity troponin I (hsTnI) were measured.

    Results: The median age of individuals was 47.8 years, 48.3% were men. The median of right-winsorized AC was 3 g/day. N=6,055 individuals developed AF (median follow-up time: 13.9 years). In a linear multivariable-adjusted Cox regression analyses, AC was linearly and positively associated with incident AF (Figure), hazard ratio (HR) per g/day 1.009, 95% confidence interval (CI) 1.007- 1.012, P<0.001. For one drink (12g) per day the HR was 1.15, CI 1.12–1.18, P<0.001. There was a high heterogeneity in associations across cohorts.

    No significant interactions of the association by Nt-proBNP and hsTnI were observed. AC was positively related to stroke risk after diagnosis of AF (HR 1.18, 95% CI 1.04–1.34, P=0.012).

    Conclusions: In contrast to other cardiovascular diseases, we did not observe a U-shaped association of alcohol with incident AF in the community, but a rather linearly increasing relation.

  • 194. Dahlen, Torsten
    et al.
    Edgren, Gustaf
    Lambe, Mats
    Hoglund, Martin
    Bjorkholm, Magnus
    Sandin, Fredrik
    Själander, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Richter, Johan
    Olsson-Stromberg, Ulla
    Ohm, Lotta
    Back, Magnus
    Stenke, Leif
    Cardiovascular Events Associated With Use of Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia: A Population-Based Cohort Study2016In: Annals of Internal Medicine, ISSN 0003-4819, E-ISSN 1539-3704, Vol. 165, no 3, p. 161-166Article in journal (Refereed)
    Abstract [en]

    Background: Tyrosine kinase inhibitors (TKIs) have increased survival dramatically for patients with chronic myeloid leukemia (CML), but continuous administration of these drugs may elicit long-term toxicity. Objective: To investigate the incidence of vascular events in patients with CML treated with first-and second-generation TKIs. Design: Retrospective cohort study using nationwide population-based registries. Setting: Sweden. Patients: All patients diagnosed with chronic-phase CML in Sweden from 2002 to 2012 and treated with a TKI, and 5 age- and sex-matched control individuals per patient. Measurements: Relative risks, expressed as incidence rate ratios comparing patients with control individuals, were calculated. Events per 1000 person-years were assessed in interdrug comparisons. Results: 896 patients, 94.4% with documented TKI treatment, were followed for a median of 4.2 years. There were 54 arterial and 20 venous events in the CML cohort, corresponding to relative risks of 1.5 (95% CI, 1.1 to 2.1) and 2.0 (CI, 1.2 to 3.3), respectively. The event rate for myocardial infarction was higher in patients treated with nilotinib or dasatinib (29 and 19 per 1000 person-years, respectively) than in those receiving imatinib (8 per 1000 person-years), although data are limited and the CIs were wide and overlapped. Among 31 patients treated with a TKI who had myocardial infarction, 26 (84%) had at least 1 major cardiac risk factor diagnosed before the event occurred. Limitations: Patients may have been exposed to multiple TKIs. Data on second-and third-generation TKIs were limited. Conclusion: An increased risk for arterial and venous vascular events was seen in patients with CML treated with a TKI. Further study is needed to determine whether the risk for myocardial infarction increases with second-generation drugs.

  • 195. Dahlström, Ulf
    et al.
    Håkansson, Jan
    Swedberg, Karl
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Adequacy of diagnosis and treatment of chronic heart failure in primary health care in Sweden2009In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 11, no 1, p. 92-98Article in journal (Refereed)
    Abstract [en]

    AIMS: We performed an observational multicentre study to obtain information of the diagnostic tools and treatments currently used in patients with chronic heart failure (CHF) in primary health care (PHC) in Sweden. Data were collected from 2093 patients in 158 randomly selected PHC centres. METHODS AND RESULTS: The mean age was 79 years. The dominating aetiology of HF was hypertension and/or ischaemic heart disease. Diagnosis was based on symptoms and/or ECG and/or chest X-ray in 69% of the patients. Treatment with a renin-angiotensin system (RAS) blocker was ongoing in 74% of the patients, but only 37% had > or = 50% of the recommended target dose. In 68%, treatment with a beta-blocker (BB) was present, but only 31% had > or = 50% of the recommended target dose. Only 42% of the patients were on treatment with an RAS blocker and a BB and only 20% had > or = 50% of the recommended target dose. CONCLUSION: The diagnostic criteria for CHF according to the European Society of Cardiology were fulfilled in only approximately 30% of the patients. In addition, evidenced-based treatments to reduce morbidity and mortality were markedly underused, particularly regarding dosing. Our findings may reflect the patients' high age and the presence of important co-morbidities.

  • 196. Dalla, Keti
    et al.
    Hallman, Caroline
    Bech-Hanssen, Odd
    Haney, Michael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Ricksten, Sven-Erik
    Strain echocardiography identifies impaired longitudinal systolic function in patients with septic shock and preserved ejection fraction2015In: Cardiovascular Ultrasound, ISSN 1476-7120, E-ISSN 1476-7120, Vol. 13, article id 30Article in journal (Refereed)
    Abstract [en]

    Background: Myocardial dysfunction is recognized in sepsis. We hypothesized that mechanical left (LV) and right (RV) ventricular function analysed using 2-dimensional speckle-tracking echocardiography in a cohort of early severe sepsis or septic shock patients, would be different to that of a group of critically ill, non-septic patients.

    Methods: Critically ill adult patients with early, severe sepsis/septic shock (n = 48) and major trauma patients with no sepsis (n = 24) were included retrospectively, as well as healthy controls (n = 16). Standard echocardiographic examinations, including right (RV) left (LV) volumes and mitral, aortic and pulmonary vein Doppler flow profiles, were retrospectively identified and the studies were then reanalysed for assessment of myocardial strain using speckle-tracking echocardiography. Endocardial tracing of the LV was performed in apical four-chamber (4-Ch), two-chamber (2-Ch), apical long-axis (3-Ch) and apical views of RV determining the longitudinal LV and RV free wall strain in each subject.

    Results: In septic patients, heart rate was significantly higher (p = 0.009) and systolic (p < 0.001) and mean arterial pressures (p < 0.001), as well as systemic vascular resistance (p < 0.001) were significantly lower when compared to the non-septic trauma group. Ninety-three per cent of the septic patients and 50 % of the trauma patients were treated with norepinephrine (p < 0.001). LV ejection fraction (LVEF) was lower in the septic patients (p = 0.019). In septic patients with preserved LVEF (>50 %, n = 34), seventeen patients (50 %) had a depressed LV global longitudinal function, defined as a LV global strain > -15 %, compared to two patients (8.7 %) in the non-septic group (p = 0.0014). In septic patients with preserved LVEF, LV global and RV free wall strain were 14 % (p = 0.014) and 17 % lower (p = 0.008), respectively, compared to the non-septic group with preserved LVEF. There were no significant differences between groups with respect to LV end-diastolic or end-systolic volumes, stroke volume, or cardiac output. There were no signs of diastolic dysfunction from the mitral or pulmonary vein Doppler profiles in the septic patients.

    Conclusions: LV and RV systolic function is impaired in critically ill patients with early septic shock and preserved LVEF, as detected by Speckle-tracking 2D echocardiography. Strain imaging may be useful in the early detection of myocardial dysfunction in sepsis.

  • 197. Damman, Peter
    et al.
    Varenhorst, Christoph
    Koul, Sasha
    Eriksson, Peter
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Heart Centre, University Hospital.
    Erlinge, David
    Lagerqvist, Bo
    James, Stefan K.
    Treatment Patterns and Outcomes in Patients Undergoing Percutaneous Coronary Intervention Treated With Prasugrel or Clopidogrel (from the Swedish Coronary Angiography and Angioplasty Registry [SCAAR])2014In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 113, no 1, p. 64-69Article in journal (Refereed)
    Abstract [en]

    Large real-world registry data are important for understanding the current use and outcomes of novel therapies. The aim of this study was to assess treatment patterns and outcomes in patients who underwent percutaneous coronary intervention (PCI) with prasugrel or clopidogrel. Consecutive patient data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) for 2010 and 2011 were used. The study population consisted of all patients with acute coronary syndromes (ACS) and those without ACS who underwent PCI and were treated with prasugrel (with or without a clopidogrel loading dose) or solely with clopidogrel. Outcomes included were 30-day mortality and in-hospital bleeding. In 2010 and 2011, 23,994 patients were treated with clopidogrel during hospitalization for their first PCI during the study period, while 2,142 patients were treated with prasugrel. Prasugrel was mainly used in patients with ST-segment elevation myocardial infarction. Hemorrhagic risk factors such as older age, female gender, and previous stroke were more common in the clopidogrel-treated patients. However, Mehran bleeding risk scores were higher in prasugrel-treated patients. In the ACS group, lower mortality was observed in the prasugrel group compared with the clopidogrel group. Mortality was comparable in patients who underwent elective angiography and PCI. In-hospital bleeding was lower in prasugrel-treated patients. In conclusion, in this real world population of patients who underwent urgent or elective PCI, prasugrel was used mainly in patients with ACS, while it was avoided in patients with characteristics indicating increased bleeding risk. Mortality and bleeding rates were lower with prasugrel than clopidogrel, probably because of patient selection.

  • 198. D'Ascenzi, F.
    et al.
    Cameli, M.
    Iadanza, A.
    Reccia, R.
    Lisi, M.
    Curci, V.
    Sinicropi, G.
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Pierli, C.
    Mondillo, S.
    Left atrial remodeling in patients undergoing transcatheter aortic valve implantation: a speckle tracking prospective study2013In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 34, no Supplement: 1, p. 338-338Article in journal (Other academic)
    Abstract [en]

    Background: Aortic Stenosis (AS) results in several Left Ventricular (LV) disturbances as well as progressive Left Atrial (LA) enlargement and dysfunction. Transcatheter Aortic Valve Implantation (TAVI) reverses LV remodelling and improves overall systolic function but its effect on LA function remains undetermined. The aim of this prospective study was toinvestigate the effects of TAVI on LA structure and function.

    Material and methods: We studied thirty-two patients with severe symptomatic AS and high surgical risk who underwent TAVI, using standard and 2-dimensional speckle-tracking echocardiography before, at 40-day and at 3-month follow-up.

    Results: Following TAVI, mean transvalvular gradient reduced (p<0.001). Both LA mean area index and LA mean volume index decreased at 40-day (16.2±6.4 vs. 12.5±2.9 cm2/m2, and 47.3±12.0 vs. 42.8±12.5 mL/m2, respectively, p<0.05) and values remained unchanged at 3 months. The reduction of LA size was accompanied by a significant increase in global PALS (14.4±3.9% vs. 19.1±4.7%, p<0.001) and global PACS (8.4±2.5% vs. 11.0±4.1%, p<0.05) at 3-month. After the procedure, LA stiffness measurements decreased and became significant at 3-month follow up (p<0.001). Pre-procedural trans-aortic mean gradient and pre-procedural LA volume were identified as predictors of global PALSincrease (p<0.0001) while the delta drop in trans-aortic mean gradient as predictors of LA volume index reduction 3 months after TAVI (p<0.0001).

    Conclusion: TAVI is associated with significant recovery of LA structure and function suggesting a reverse cavity remodelling. Such functional recovery is determined by the severity of pre-procedural valve stenosis.

  • 199.
    D'Ascenzi, Flavio
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Atrial function and loading conditions in athletes2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Intensive training is associated with hemodynamic changes that typically induce an enlargement of cardiac chamber. Despite LA dilatation in athletes has been interpreted as a benign adaptation, little evidence is available. The aim of this thesis is to demonstrate that LA size changes in response to alterations in loading conditions and to analyse atrial myocardial function in athletes through the application of novel echocardiographic techniques.

    We found that top-level athletes exhibit a dynamic morphological and functional LA remodelling, induced by training, with an increase in reservoir and conduit volumes, but stable active volume. Training causes an increase in biatrial volumes which is accompanied by normal filling pressures and stiffness. These changes in atrial morphology are not associated with respective electrical changes. Extending the evidence from adult athletes to children, we found that training-induced atrial remodelling can occur in the early phases of the sports career and is associated with a preserved biatrial function. Finally, in a meta-analysis study of the available evidence we demonstrated that atrial function and size are not affected by aging.

    In conclusions, athlete’s heart is characterized by a physiological biatrial enlargement. This adaptation occurs in close association with LV cavity enlargement, is dynamic and reversible. This increase in biatrial size is not intrinsically an expression of atrial dysfunction. Indeed, in athletes the atria are characterized by a preserved reservoir function, normal myocardial stiffness, and dynamic changes in response to different loading conditions.

  • 200.
    D'Ascenzi, Flavio
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    The impact of aging on left atrial size and function: a systematic review and meta-analysis in healthy subjectsManuscript (preprint) (Other academic)
    Abstract [en]

    Background. The cardiovascular system is affected by aging, however conflicting results cloud this relationship and data on LA myocardial function and aging are scanty. The aim of this study was to evaluate the impact of aging on LA size and function in healthy subjects.

    Methods. We conducted a systematic literature search of MEDLINE database. We included only studies evaluating healthy subjects, with age ranged between 18 and 80 years. Parameters were compared among 4 age groups, <30, 30-45, >45-60, >60 years.

    Results. Three hundred twenty-six studies met the inclusion criteria and the final population consisted of 62,821 subjects. LA antero-posterior diameter and LA volume gradually increased with aging, however LA volume index did not differ among groups. LA ejection fraction measured by three-dimensional echocardiography modestly reduced with age (p=0.049), but respective measurements derived by two-dimensional echocardiography did not (p=0.94). LA reservoir function, measured by strain, did not differ among the groups. Left ventricular (LV) size and function were not different among groups, except LV mass index. A decrease in E/A ratio and an increase in E/e’ ratio with advancing age (p<0.0001 and p=0.001, respectively).

    Conclusions. In healthy subjects LA volume index is not influenced while LA antero-posterior diameter and absolute volumes increase with advancing age. Neither LA deformation nor systolic function measures were affected by age. Thus, an increase in LA volume index and a decrease in LA reservoir function should be considered as an expression of pathology rather than part of normal aging.

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