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Insights into left atrial response to pressure and volume overload
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Department of Cardiovascular Disease, University of Siena, Italy, . (Cardiology)
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The general purpose of this thesis is to establish the ability of Speckle Tracking Echocardiography (STE) in assessing left atrial (LA) response to pressure and volume overload respectively in aortic stenosis (AS) and mitral regurgitation (MR), and to evaluate its accuracy in predicting LA and right ventricular (RV) fibrosis in patients with end-stage heart failure (HF) undergoing heart transplantation (HTx).

I demonstrated that assessment of left ventricular (LV) long axis systolic velocity and amplitude of excursion is more sensitive than simple determination of ejection fraction (EF) for revealing the beneficial impact of MR surgery on overall LV systolic performance.

Severe symptomatic AS is associated with LA enlargement and compromised mechanical function with a high incidence of peri-operative atrial fibrillation (AF). Valve replacement reverses these abnormalities and regains normal atrial function, a behaviour which is directly related to the severity of pre-operative LV outflow tract obstruction. Early identification of LA size and function disturbances, as shown by myocardial strain measurements might contribute to better patient’s recruitment for a safe valve replacement.

In late stage HF patients, the right ventricle is enlarged, with reduced systolic function due to significant myocardial fibrosis. RV free wall myocardial deformation is the most accurate function measure that correlates with the extent of RV myocardial fibrosis and functional capacity.

In patients with preserved EF, severe MR masks LV and LA myocardial dysfunction and correlates with symptoms and post-operative cavity function instability. Three months after MVR, the underlying myocardial disturbances are unmasked suggesting that most pre-operative measurements are subject to loading conditions. Finally LA volume and PALS remain the main predictors of post-operative AF, thus should be used for stratifying surgical risk.

STE has been shown to accurately determine the severity of impairment of LA myocardial function shown by suppressed PALS which was the strongest predictor of the presence and extent of fibrosis, over and above other structure and function parameters. These findings may assist in better stratifying patients with end stage HF and identifying particularly those requiring HTx.

Place, publisher, year, edition, pages
Umeå: University of Umeå , 2016. , 138 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1863
Keyword [en]
Keywords Mitral regurgitation, aortic stenosis, speckle tracking echocardiography, heart transplantation, left atrial strain, left ventricualr function, right ventricular function, myocardial fibrosis
National Category
Cardiac and Cardiovascular Systems
Identifiers
URN: urn:nbn:se:umu:diva-127294ISBN: 978-91-7601-610-7OAI: oai:DiVA.org:umu-127294DiVA: diva2:1044689
Public defence
2016-12-01, Sal C, Unod T9, Norrlands Universitetssjukhus, Umeå, 09:00 (English)
Opponent
Supervisors
Available from: 2016-11-10 Created: 2016-11-04 Last updated: 2016-11-21Bibliographically approved
List of papers
1. Mitral annular longitudinal function preservation after mitral valve repair: the MARTE study
Open this publication in new window or tab >>Mitral annular longitudinal function preservation after mitral valve repair: the MARTE study
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2012 (English)In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 157, no 2, 212-215 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: In patients with chronic mitral regurgitation (MR), undergoing surgical mitral valve repair, current Guidelines only recommend standard echocardiographic indices i.e. left ventricular (LV) ejection fraction (EF), and LV end-systolic and end-diastolic diameters as preoperative variables. However LV EF is often preserved until advanced stages of the valve disease. Aim of this study was to evaluate changes in LV systolic longitudinal function, 3months after mitral valve repair in patients with chronic degenerative MR and normal preoperative EF.

METHODS: We measured M-mode mitral lateral annulus systolic excursion (MAPSE) and Tissue Doppler (TD) peak systolic annular velocity (S(m)) in 31 patients with moderate to severe MR and normal EF (59.9±4.7%) candidates for mitral valve repair, preoperatively and 3months after surgery.

RESULTS: After mitral valve repair, S(m) increased from 7.8±1.4 to 9.6±2.2cm/s (p<0.0001) and MAPSE increased from 1.33±0.26 to 1.55±0.25cm (p=0.0013). EF decreased from 59.9±4.7 to 51.3±5.9% (p<0.0001). As expected, LV diameters and volumes, wall thicknesses, midwall fractional shortening (mFS), and left atrial (LA) size were all reduced after surgery.

CONCLUSIONS: This study suggests that assessment of LV long axis systolic velocity and amplitude of excursion by echocardiography is more sensitive than simple determination of EF for revealing the beneficial impact of MR surgery on overall systolic function.

Place, publisher, year, edition, pages
Elsevier, 2012
Keyword
Longitudinal function; Mitral valve
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-39687 (URN)10.1016/j.ijcard.2010.12.054 (DOI)21194764 (PubMedID)
Available from: 2011-02-03 Created: 2011-02-03 Last updated: 2016-11-09Bibliographically approved
2. Severity of aortic stenosis predicts early post-operative normalization of left atrial size and function detected by myocardial strain
Open this publication in new window or tab >>Severity of aortic stenosis predicts early post-operative normalization of left atrial size and function detected by myocardial strain
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2013 (English)In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 167, no 4, 1450-1455 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Aortic stenosis (AS) causes significant disturbances in left ventricular (LV) and left atrial (LA) function irrespective of the extent of myocardial hypertrophy which associates the increased afterload. We hypothesize that aortic valve replacement (AVR) and removal of LV outflow tract obstruction should result in LA size and function recovery, even partial, and were set to study this in a group of patients with AVR for AS.

METHODS: Peak atrial longitudinal strain (PALS) was evaluated in 43 patients with severe isolated AS and normal EF (56.6±3.8%) and no obstructive coronary artery disease candidates for AVR, pre-operatively and then 40days and 3months after surgery. Results were compared with those from 34 age- and gender-matched healthy controls.

RESULTS: LVEF remained unchanged and LV mass regressed after AVR. Global PALS was reduced pre-operatively and increased 40days after surgery (p=0.002) and showed only a slight further increase at 3months follow-up (p<0.0001). Indexed LA volume was increased before surgery, but significantly fell 40days after surgery (p<0.0001) and showed only a slight further reduction after 3months (p<0.0001). Trans-aortic mean gradient change after surgery was the only independent predictor of the recovery of LA size and function.

CONCLUSIONS: AVR reverses LA abnormalities and regains normal atrial function, a behavior which is directly related to the severity of pre-operative LV outflow tract obstruction. Early identification of LA size enlargement and functional disturbances might contribute to better patient's recruitment for AVR.

National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-65093 (URN)10.1016/j.ijcard.2012.04.057 (DOI)000323566800071 ()22560912 (PubMedID)
Available from: 2013-02-05 Created: 2013-02-05 Last updated: 2016-11-09Bibliographically approved
3. RV Longitudinal Deformation Correlates With Myocardial Fibrosis in Patients With End-Stage Heart Failure
Open this publication in new window or tab >>RV Longitudinal Deformation Correlates With Myocardial Fibrosis in Patients With End-Stage Heart Failure
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2015 (English)In: JACC Cardiovascular Imaging, ISSN 1936-878X, E-ISSN 1876-7591, Vol. 8, no 5, 514-522 p.Article in journal (Refereed) Published
Abstract [en]

Objectives: This study was performed to determine the accuracy of right ventricular (RV) longitudinal strain (LS) in predicting myocardial fibrosis in patients with severe heart failure (HF) undergoing heart transplantation. Background: RVLS plays a key role in the evaluation of its systolic performance and clinical outcome in patients with refractory HF. Methods: We studied 27 patients with severe systolic HF (ejection fraction ≤25% and New York Heart Association functional class III to IV, despite full medical therapy and cardiac resynchronization therapy) using echocardiography before heart transplantation. RV free wall LS, right atrial LS, sphericity index (SI), and tricuspid annular plane systolic excursion (TAPSE) were all measured. Upon removal of the heart, from the myocardial histologic analysis, the ratio of the fibrotic to the total sample area determined the extent of fibrosis (%). Results: RV myocardial fibrosis correlated with RV free wall LS (r = 0.80; p < 0.0001), SI (r = 0.42; p = 0.01) and VO2 max (r = –0.41; p = 0.03), with a poor correlation with TAPSE (r = –0.34; p = 0.05) and right atrial LS (r = –0.37; p = 0.03). Stepwise multivariate analysis showed that RV free wall LS (β = 0.701, p < 0.0001) was independently associated with RV fibrosis (overall model R2 = 0.64, p < 0.0001). RV free wall LS was the main determinant of myocardial fibrosis. In the subgroup of patients with severe RV fibrosis, RV free wall LS had the highest diagnostic accuracy for detecting severe myocardial fibrosis (area under the curve = 0.87; 95% confidence interval: 0.80 to 0.94). Conclusions: In late-stage HF patients, the right ventricle is enlarged, with reduced systolic function due to significant myocardial fibrosis. RV free wall myocardial deformation is the most accurate functional measure that correlates with the extent of RV myocardial fibrosis and functional capacity.

Place, publisher, year, edition, pages
Elsevier, 2015
Keyword
heart failure, myocardial fibrosis, right ventricle
National Category
Cardiac and Cardiovascular Systems Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:umu:diva-105267 (URN)10.1016/j.jcmg.2014.12.026 (DOI)000355068500003 ()25890585 (PubMedID)
Available from: 2015-06-22 Created: 2015-06-22 Last updated: 2016-11-09
4. Mitral regurgitation severity correlates with symptoms and extent of left atrial dysfunction: Effect of mitral valve repair
Open this publication in new window or tab >>Mitral regurgitation severity correlates with symptoms and extent of left atrial dysfunction: Effect of mitral valve repair
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2016 (English)Manuscript (preprint) (Other academic)
Abstract [en]

Purpose: We aimed to assess the relationship between mitral regurgitation (MR) severity, symptoms and left atrial (LA) structure and function, before and after mitral valve repair (MVR).

Methods: Global peak atrial longitudinal strain (PALS) was evaluated in 37 patients with severe symptomatic MR and preserved left ventricular (LV)EF (60.4±4.6%) before and 3 months after MVR and was compared with values from 30 age- and gender-matched controls.

Results: Before surgery, global PALS was reduced and indexed LA volume was increased (p<0.0001 for both). After MVR, both fell (p=0.001 and p=0.05, respectively) as did LVEF, longitudinal strain (LS) (p=0.05 and p<0.001, respectively) and LV mass (LVM) (p<0.0001).

Before surgery, LA volume correlated modestly with LV end-diastolic volume (R=0.51; p=0.01); EROA correlated with PALS (R=-0.69,p<0.001) and with LV LS (R=0.54,p=0.01); and NYHA class correlated with PALS (R=-0.69,p<0.001), EROA (R=0.69, p<0.001), and with LA volume (R=0.51, p=0.04). LA volume was the strongest predictor of global PALS reduction (p<0.001) while global PALS was the main predictor of post-operative atrial fibrillation (AF) (p<0.001),

Conclusions: In patients with severe MR, EROA correlate with symptoms and LA PALS which itself predicts the occurrence of post-operative AF. Strain values were superior to 2D-data for the prediction of post-operative AF.

 

National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-127291 (URN)
Available from: 2016-11-04 Created: 2016-11-04 Last updated: 2016-11-09
5. Reduced myocardial strain is the best predictor of left atrial fibrosis and symptoms in patients undergoing heart transplantation
Open this publication in new window or tab >>Reduced myocardial strain is the best predictor of left atrial fibrosis and symptoms in patients undergoing heart transplantation
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2016 (English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: Left ventricular systolic dysfunction and raised diastolic pressures contribute to progressive left atrial (LA). We aimed to assess LA peak atrial longitudinal strain (PALS), in predicting the extent of LA fibrosis in patients with end-stage heart failure (HF) undergoing heart transplantation (HTx).

Methods: We studied 48 patients with severe systolic HF (EF≤25% and NYHA class III-IV) before HTx. PALS, LA volume and LA stiffness were all measured. From the LA myocardial histological analysis, the ratio of fibrotic to total sample area determined the extent of fibrosis (%). Right heart catheterization and cardiopulmonary exercise testing were also assessed.

 

Results: LA fibrosis correlated strongly with PALS (R=-0.76; p<0.0001) and NYHA class (R=0.73; p<0.0001) and to a lesser extent with VO2 max (R=-0.65; p=0.001), LA stiffness (R=0.58; p=0.001), PAoP (R=0.51; p=0.03), E/e′ (R=0.55; p=0.01) and E/A (R=0.46; p=0.01). Global PALS correlated modestly with VO2 max (R=0.53; p=0.001) and LA volume (R=-0.48; p=0.01) and weakly with E/e′ (R=-0.36; p=0.03). Multivariate regression analysis identified global PALS as the main determinant of LA myocardial fibrosis (β =-0.62, p<0.001). A cut off value of 7.6% gave an AUC of 0.79 on the ROC curve with a sensitivity of 87% and specificity of 84% in predicting >50% myocardial fibrosis.

Conclusions:LA PALS is the most accurate LA function parameter that correlates with the extent of myocardial fibrosis in patients with advanced systolic HF requiring HTx.PALS of 7.6% could be used as a cut off value for identifying patients with severe LA fibrosis.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-127292 (URN)
Available from: 2016-11-04 Created: 2016-11-04 Last updated: 2016-11-09

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