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The clinical value of total isovolumic time
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The objective of this thesis is to evaluate the use of Doppler echocardiography markers ofglobal dyssynchrony [total isovolumic time (t-IVT)] in the following 6 studies: 1) Its prognostic role in predicting cardiac events in patients undergoing CABG surgery,compared with conventional global systolic and diastolic measurements. 2) Its additional value in predicting six minute walk test (6-MWT) in patients with leftventricular (LV) ejection fraction (EF) <45%. 3) Its prognostic value in comparison with other clinical, biochemical and echocardiographicvariables in patients with chronic systolic heart failure (HF). 4) The relationship between 6-MWT and cardiac function measurements in a consecutivegroup of patients, irrespective of EF and to identify predictors of exercise capacity. 5) To investigate the effect of age on LV t-IVT and Tei index compared with conventionalsystolic and diastolic parameters. 6) To assess potential additional value of markers of global LV dyssynchrony in predictingcardiac resynchronization therapy (CRT) response in HF patients.

Study I

Methods: This study included 74 patients before routine CABG who were followed up for18±12 months. Results: At follow-up, 29 patients were hospitalized for a cardiac event or died. LV-ESD wasgreater (P=0.003), fractional shortening (FS) lower (p<0.001), E:A ratio and Tei index higher(all P<0.001), and t-IVT longer (P<0.001) in patients with events. Low FS [0.66 (0.50–0.87),P<0.001], high E:A ratio [l4.13 (1.17–14.60), P=0.028], large LV-ESD [0.19 (0.05–0.84),P=0.029], and long t-IVT [1.37 (1.02–1.84), P=0.035] predicted events and deaths. Conclusion: Despite satisfactory surgical revascularization, long t-IVT and systolicdysfunction suggest persistent ventricular dyssynchrony that contributes to post-CABGcardiac events.

Study II

Methods: We studied 77 patients (60±12 year, and 33.3% females) with stable HF using 6-MWT.iii Results: E’ wave (r=0.61, p<0.001), E/e’ ratio (r=-0.49, p<0.001), t-IVT (r=-0.44, p<0.001),Tei index (r=-0.43, p<0.001) and NYHA class (r=-0.53, p<0.001) had the highest correlationwith the 6-MWT distance. In multivariate analysis, only E/e’ ratio [0.800 (0.665-0.961),p=0.017], and t-IVT [0.769 (0.619-0.955), p=0.018] independently predicted poor 6-MWTperformance (<300m). Conclusions: In HF, the higher the filling pressures and the more dyssynchronous the LV, thepoorer is the patient’s exercise capacity.

Study III

Methods: We studied 107 systolic HF patients; age 68±12 year, 25% females and measuredplasma NT-pro-BNP. Results: Over a follow-up period of 3718 months, t-IVT ≥12.3 sec/min, mean E/Em ratio≥10, log NT-pro-BNP levels ≥2.47 pg/ml and LV EF ≤32.5% predicted clinical events. Theaddition of t-IVT and NT-pro-BNP to conventional clinical and echocardiographic variablessignificantly improved the χ2 for the prediction of outcome from 33.1 to 38.0, (p<0.001). Conclusions: Prolonged t-IVT adds to the prognostic stratification of patients with systolicHF.

Study IV

Methods: We studied 147 HF patients (61±11 year, 50.3% male) with 6-MWT.Results: The 6-MWT correlated with t-IVT (r=-0.49, p<0.001) and Tei index (r=-0.43,p<0.001) but not with any of the other clinical or echocardiographic parameters. Group Ipatients (<300m) had lower Hb (p=0.02), lower EF (p=0.003), larger left atrium (p=0.02),thicker septum (p=0.02), lower A wave (p=0.01) and lateral wall a’ (p=0.047), longerisovolumic relaxation time (r=0.003) and longer t-IVT (p= 0.03), compared with Group II(>300m). Only t-IVT ratio [1.257 (1.071-1.476), p=0.005], LV EF [0.947 (0.903-0.993),p=0.02], and E/A ratio [0.553 (0.315-0.972), p=0.04] independently predicted poor 6-MWTperformance. Conclusion: In HF, the limited 6-MWT is related mostly to severity of global LVdyssynchrony, more than EF or raised filling pressures.

Study V

Methods: We studied 47 healthy individuals (age 62±12 year, 24 female), arbitrarilyclassified into: M (middle age), S (seniors), and E (elderly). Results: Age strongly correlated with t-IVT (r=0.8, p<0.001) and with Tei index (r=0.7,p<0.001), E/A ratio (r=-0.6, p<0.001), but not with global or segmental systolic function measurements or QRS duration. The normal upper limit of the t-IVT (95% CI) for the three groups was 8.3 s/min, 10.5 s/min and 14.5 s/min, respectively, being shorter in the S compared with the E group (p=0.001). T-IVT correlated with A wave (r=0.66, p<0.001), E/Aratio (r=-0.56, p<0.001), septal e’ (r=-0.49, p=0.001) and septal a’ (r=0.4, p=0.006), but notwith QRS. Conclusions: In normals, age is associated with exaggerated LV global dyssynchrony anddiastolic function disturbances, but systolic function remains unaffected.

Study VI

Methods: We studied 103 HF patients (67±12 year, 82.5% male) recruited for CRTtreatment. Results: Prolonged t-IVT [0.878 (0.802-0.962), p=0.005], long QRS duration [0.978 (0.960-0.996), p=0.02] and high tricuspid regurgitation pressure drop (TRPD) [1.047 (1.001-1.096),p=0.046] independently predicted response to CRT. A t-IVT ≥11.6 s/min was 67% sensitiveand 62% specific (AUC 0.69, p=0.001) in predicting CRT response. Respective values for aQRS ≥ 151ms were 66% and 62% (AUC 0.65, p=0.01). Combining the two variables had asensitivity of 67% but higher specificity of 88% in predicting CRT response. In atrialfibrillation (AF) patients, only prolonged t-IVT ≥11 s/min [0.690 (0.509-0.937), p=0.03]independently predicted CRT response with a sensitivity of 69% and specificity of 79% (AUC0.78, p=0.015). Conclusion: Combining prolonged t-IVT and broad QRS had higher specificity in predictingresponse to CRT, with the former the sole predictor of response in AF patients.

Place, publisher, year, pages
Umeå: Umeå universitet, 2014. 89 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1656
Keyword [en]
Heart failure, cardiac resynchronization therapy, predictors, echocardiography, total isovolumic time, six-minute walk test, left ventricular dyssynchrony
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-88994 (URN)978-91-7601-086-0 (ISBN)oai:DiVA.org:umu-88994 (OAI)diva2:718105 (DiVA)
Public defence
2014-06-10, Room D, Unod T9, Norrlands universitetssjukhus, Umea, 09:00 (English)
Opponent
Supervisors
Available from2014-05-20 Created:2014-05-19 Last updated:2014-05-20Bibliographically approved
List of papers
1. Prolonged total isovolumic time predicts cardiac events following coronary artery bypass surgery
Open this publication in new window or tab >>Prolonged total isovolumic time predicts cardiac events following coronary artery bypass surgery
2008 (English)In: European Journal of Echocardiography, ISSN 1525-2167, E-ISSN 1532-2114, Vol. 9, no 6, 779-783Article in journal (Refereed) Published
Abstract [en]

AIMS: Left ventricular (LV) systolic dysfunction may be associated with compromised stroke volume, which may be caused by asynchrony, reflected on the prolongation of isovolumic time (t-IVT). To assess the prognostic role of Doppler echocardiographic measurements in predicting cardiac events after coronary artery bypass grafting (CABG).

METHODS AND RESULTS: The study included 74 patients undergoing routine CABG. A pre-CABG Doppler echocardiographic assessment of LV dimensions, filling and ejection was performed and t-IVT was determined as [60 - (total ejection time + total filling time)]. Follow-up period was 18 +/- 12 months. Of the 74 patients (age 65 +/- 16 years, 59 males), 29 underwent hospital admission for a cardiac event or died. There were no differences in age, gender, incidence of previous infarct or mitral regurgitation, LV-EDD (left ventricular end-diastolic dimension), left atrial or right ventricular size in patients with cardiac events compared with those without events. Left ventricular end-systolic dimension (LV-ESD) was greater (4.5 +/- 0.9 vs. 3.9 +/- 0.9 cm, P = 0.003), fractional shortening (FS) was lower (21 +/- 4 vs. 32 +/- 8%), E:A ratio and Tei index were higher (2.1 +/- 0.8 vs. 1.0 +/- 0.6 and 0.9 +/- 0.3 vs. 0.6 +/- 0.3, all P < 0.001), and t-IVT was longer (16 +/- 5 vs.10 +/- 4 s/min, P < 0.001) in patients with events. Multivariate predictors of post-CABG events (odds ratio 95% confidence interval) were low FS [0.66 (0.50-0.87), P < 0.001], high E:A ratio [l4.13 (1.17-14.60), P = 0.028], large LV-ESD [0.19 (0.05-0.84), P = 0.029], and long t-IVT [1.37 (1.02-1.84), P = 0.035].

CONCLUSION: Despite satisfactory surgical revascularization, long t-IVT and systolic dysfunction suggest persistent ventricular dyssynchrony that contributes to post-CABG cardiac events. Early assessment of such patients for potential benefit from electrical resynchronization may optimize their cardiac performance and hence clinical outcome.

Publisher, range
Oxford University Press, 2008
Keyword
Coronary artery disease, Coronary artery bypass grafting, Doppler echocardiography, Total isovolumic time
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-23135 (URN)10.1093/ejechocard/jen146 (DOI)000260381500017 ()18490287 (PubMedID)
Available from2009-06-01 Created:2009-06-01 Last updated:2014-06-19Bibliographically approved
2. Left ventricular asynchrony and raised filling pressure predict limited exercise performance assessed by 6 minute walk test
Open this publication in new window or tab >>Left ventricular asynchrony and raised filling pressure predict limited exercise performance assessed by 6 minute walk test
Show others...
2009 (English)In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 146, no 3, 385-389Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Six minute walking test (6-MWT) may serve as a reproducible test for assessing exercise capacity in heart failure (HF) patients and can be clinically predicted. We aimed in this study to ascertain if global markers of ventricular asynchrony can predict 6MWT distance in a group of patients with HF and left ventricular (LV) ejection fraction (EF) <45%.

METHODS AND RESULTS: This study included 77 consecutive patients (60+/-12 years) with stable HF. LV end-diastolic and end-systolic dimensions, shortening fraction (SF), EF, myocardial velocities, t-IVT, and Tei index were measured, as well as 6-MWT distance. Patients with limited exercise performance (</=300 m) had lower SF (p=0.02) and EF (p=0.017), longer t-IVT (p=0.001), higher Tei index (p=0.002) and higher E/E' ratio (p<0.001) compared with good performance patients. In multivariate analysis, only E/E' ratio [0.800 (0.665-0.961), p=0.017], and t-IVT [0.769 (0.619-0.955), p=0.018] independently predicted poor exercise performance.

CONCLUSIONS: In heart failure patients, the higher the filling pressures and the more asynchronous the left ventricle, the poorer is the patient's exercise capacity. These findings highlight specific LV functional disturbances that should be targeted for better optimization of medical and/or electrical therapy.

Keyword
Six-minute walk test, doppler echocardiography, restrictive filling, left ventricular asynchrony
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-30994 (URN)10.1016/j.ijcard.2009.07.018 (DOI)000286460500022 ()19699003 (PubMedID)
Available from2010-01-26 Created:2010-01-26 Last updated:2014-06-19Bibliographically approved
3. Independent and incremental prognostic value of Doppler-derived left ventricular total isovolumic time in patients with systolic heart failure
Open this publication in new window or tab >>Independent and incremental prognostic value of Doppler-derived left ventricular total isovolumic time in patients with systolic heart failure
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2009 (English)In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 148, no 3, 271-275Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: A prolonged total isovolumic time (T-IVT) has been shown to be associated with worsening survival in patients submitted to coronary artery surgery. However, it is not known whether it has prognostic significance in patients with chronic systolic heart failure (HF).

AIM: To determine the prognostic value of T-IVT in comparison with other clinical, biochemical and echocardiographic variables in patients with chronic systolic HF.

METHODS: Patients (n=107; age 68+/-12years, 25% women) with chronic systolic HF, left ventricular ejection fraction (EF) <45%, and sinus rhythm, underwent a complete Doppler echocardiographic study, that included tissue Doppler long axis velocities and total isovolumic time (T-IVT), determined as [60-(total ejection time+total filling time)]. Plasma N-terminal pro-B natriuretic peptide (NT-pro-BNP) was also measured. The associations of dichotomous variables selected according to the Receiver Operator Characteristic analysis were assessed using the Cox proportional hazard model.

RESULTS: Follow-up period was 37+/-18months. Multivariate predictors of events were T-IVT >/=12.3% s/min, mean E/E(m) ratio >/=10, log NT-pro-BNP levels >/=2.47pg/ml and LV EF</=32.5%. On Kaplan-Meier analysis, patients with prolonged T-IVT, high mean E/E(m) ratio, increased NT-pro-BNP levels and decreased LV EF had a worse outcome compared with those without. The addition of T-IVT and NT-pro-BNP to conventional clinical and echocardiographic variables significantly improved the chi-square for the prediction of the outcome from 33.1 to 38.0, (P<0.001).

CONCLUSIONS: Prolonged T-IVT added to the prognostic stratification of patients with systolic HF.

Keyword
Heart failure, doppler echocardiography, left ventricular asynchrony, left ventricular filling pressures
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-31019 (URN)10.1016/j.ijcard.2009.09.567 (DOI)000289716400013 ()19948365 (PubMedID)
Available from2010-01-27 Created:2010-01-27 Last updated:2014-06-19Bibliographically approved
4. Left ventricular markers of global dyssynchrony predict limited exercise capacity in heart failure, but not in patients with preserved ejection fraction
Open this publication in new window or tab >>Left ventricular markers of global dyssynchrony predict limited exercise capacity in heart failure, but not in patients with preserved ejection fraction
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2012 (English)In: Cardiovascular Ultrasound, ISSN 1476-7120, Vol. 10, 36-Article in journal (Refereed) Published
Abstract [en]

Background: The aim of this study was to prospectively examine echocardiographic parameters that correlate and predict functional capacity assessed by 6 min walk test (6-MWT) in patients with heart failure (HF), irrespective of ejection fraction (EF).

Methods: In 147 HF patients (mean age 61 +/- 11 years, 50.3% male), a 6-MWT and an echo-Doppler study were performed in the same day. Global LV dyssynchrony was indirectly assessed by total isovolumic time - t-IVT [in s/min; calculated as: 60 - (total ejection time + total filling time)], and Tei index (t-IVT/ejection time). Patients were divided into two groups based on the 6-MWT distance (Group I: <= 300 m and Group II: > 300 m), and also in two groups according to EF (Group A: LVEF >= 45% and Group B: LVEF <45%).

Results: In the cohort of patients as a whole, the 6-MWT correlated with t-IVT (r = -0.49, p < 0.001) and Tei index (r = -0.43, p < 0.001) but not with any of the other clinical or echocardiographic parameters. Group I had lower hemoglobin level (p = 0.02), lower EF (p = 0.003), larger left atrium (p = 0.02), thicker interventricular septum (p = 0.02), lower A wave (p = 0.01) and lateral wall late diastolic myocardial velocity a' (p = 0.047), longer isovolumic relaxation time (r = 0.003) and longer t-IVT (p = 0.03), compared with Group II. In the patients cohort as a whole, only t-IVT ratio [1.257 (1.071-1.476), p = 0.005], LV EF [0.947 (0.903-0.993), p = 0.02], and E/A ratio [0.553 (0.315-0.972), p = 0.04] independently predicted poor 6-MWT performance (< 300 m) in multivariate analysis. None of the echocardiographic measurements predicted exercise tolerance in HFpEF.

Conclusion: In patients with HF, the limited exercise capacity, assessed by 6-MWT, is related mostly to severity of global LV dyssynchrony, more than EF or raised filling pressures. The lack of exercise predictors in HFpEF reflects its multifactorial pathophysiology.

Publisher, range
BioMed Central, 2012
Keyword
Six-minute walk test, Doppler echocardiography, LV function and dyssynchrony
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-64458 (URN)10.1186/1476-7120-10-36 (DOI)000312982700001 ()
Available from2013-02-04 Created:2013-01-29 Last updated:2014-05-20Bibliographically approved
5. Left ventricular global dyssynchrony is exaggerated with age
Open this publication in new window or tab >>Left ventricular global dyssynchrony is exaggerated with age
2013 (English)In: International Cardiovascular Forum, Vol. 1, no 1, 47-51Article in journal (Refereed) Published
Abstract [en]

Background and Aim. Total isovolumic time (t-IVT) and Tei index both reflect global left ventricular (LV) dyssynchrony. They have been shown to be sensitive in responding to myocardial revascularization and in predicting clinical outcome in heart failure patients. Since most these patients are senior, determining the exact effect of age on such parameters remains mandatory. The aim of this study was to investigate the effect of age on LV t-IVT and Tei index compared with conventional systolic and diastolic parameters in normal individuals.

Methods. We studied 47 healthy individuals, mean age 62±12 years (24 female), who were arbitrarily classified into three groups: M (middle age), S (seniors), and E (elderly), using spectral Doppler echocardiography and tissue-Doppler imaging. We studied the interrelation between age, LV systolic and diastolic function parameters as well as t-IVT [60 – (total ejection time + total filling time) in s/min], and Tei index (T-IVT/ejection time).

Results. LV ejection fraction was 68±6%, E/A ratio 1±0.4, filling time 538±136ms, ejection time 313±26ms, t-IVT 7.7±2.6 s/min and Tei index 0.41±0.14. Age strongly correlated with t-IVT (r=0.8, p<0.001) and with Tei index (r=0.7, p<0.001) but not with QRS duration. Age also correlated with E/A ratio (r=-0.6, p<0.001), but not with global or segmental systolic function measurements. Mean values for t-IVT were 5.5 (95% CI, 4.6-6.3 s/min) for M, 6.9 (95% CI, 6.0-7.8 s/min) for S and 9.5 (95% CI, 8.4-10.6 s/min) for E groups. The corresponding upper limit of the t-IVT 95% normal CI (calculated as mean ±2SD) for the three groups was 8.3 s/min, 10.5 s/min and 14.5 s/min, respectively. The upper limit of normal t-IVT 95% CI was significantly shorter in the S compared with the E group (p=0.001). T-IVT correlated with A wave (r=0.66, p<0.001), E/A ratio (r=-0.56, p<0.001), septal e’ (r=-0.49, p=0.001) and septal a’ (r=0.4, p=0.006), but not with QRS.

Conclusions. In normals, age is associated with exaggerated LV global dyssynchrony and diastolic function disturbances, but systolic function remains unaffected. The strong relationship between age and t-IVT supports its potential use as a marker of global LV dyssynchrony. In addition, variations in the upper limit of normal values, particularly in the elderly may have significant clinical applications in patients recommended for CRT treatment.

Publisher, range
New York: , 2013
Keyword
Total isovolumic time, age, LV dyssynchrony, Doppler echocardiography
National Category
Cardiac and Cardiovascular Systems
Research subject
Cardiology
Identifiers
urn:nbn:se:umu:diva-88469 (URN)
Available from2014-05-06 Created:2014-05-06 Last updated:2014-05-20Bibliographically approved
6. Combining electrical and global mechanical markers of LV dyssynchrony optimizes patient selection for cardiac resynchronization therapy
Open this publication in new window or tab >>Combining electrical and global mechanical markers of LV dyssynchrony optimizes patient selection for cardiac resynchronization therapy
Show others...
2014 (English)In: Article in journal (Refereed) Submitted
Keyword
Cardiac resynchronization therapy, heart failure, predictors, echocardiography, total isovolumic time
National Category
Cardiac and Cardiovascular Systems
Research subject
Cardiology
Identifiers
urn:nbn:se:umu:diva-88473 (URN)
Available from2014-05-06 Created:2014-05-06 Last updated:2014-07-11Bibliographically approved

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