Differential effects of afterload on left ventricular long- and short-axis function: Insights from a clinical model of patients with aortic valve stenosis undergoing aortic valve replacement

doi:10.1016/j.ahj.2009.07.008

American Heart Journal

Volume 158, Issue 4, October 2009, Pages 540-545

https://doi.org/10.1016/j.ahj.2009.07.008 Get rights and content

Background

The effects of left ventricular (LV) afterload on longitudinal versus circumferential ventricular mechanics are largely unknown. Our objective was to examine changes in LV deformation before and early after aortic valve replacement (AVR) in patients with severe aortic valve stenosis (AS).

Methods

Paired echocardiographic studies before and early (7 ± 3 days) after AVR were analyzed in 45 patients (age 67 ± 12 years, 49% men) with severe AS and normal LV ejection fraction without segmental wall motion abnormalities. Longitudinal myocardial function was assessed from 3 apical views (average of 18 segments). Circumferential function was assessed at mid and apical levels (averaging 6 segments per view). Strain, strain rate (SR), and LV twist (relative rotation of the mid and apex) were measured using 2-dimensional strain software.

Results

Early post-AVR, (1) LV size and LV ejection fraction did not change; (2) longitudinal systolic strain, which was lower than normal before AVR, increased (−12.8 ± 1.7 to −15.9 ± 2.2, P < .05), whereas mid-LV circumferential strain, which was higher than normal, decreased (−27.0 ± 5.1 to −22.3 ± 4.9, P < .05); (3) longitudinal early diastolic SR increased (0.6 ± 0.1 to 0.7 ± 0.2, P < .05), whereas mid-LV circumferential diastolic SR decreased (1.2 ± 0.5 to 1.0 ± 0.3, P < .05); and (4) LV twist increased (3.7° ± 2.1° to 6.1° ± 2.9°, P < .05).

Conclusions

Aortic valve stenosis causes differential changes in longitudinal and circumferential mechanics that partially normalize after AVR. These findings provide new insights into the mechanical adaptation of the LV to chronic afterload elevation and its response to unloading.

Section snippets

Study population

A total of 181 patients underwent AVR between January 2004 and December 2007 at our institution. Of these, 50 patients fulfilled the following criteria: (1) available echocardiographic studies before and early post-AVR in digital imaging and communications in medicine (DICOM) format; (2) normal baseline LVEF (≥ 55%), without segmental wall motion abnormalities; and (3) no other significant valvular heart disease. In 5 patients, echocardiographic studies did not meet the threshold criteria for

Baseline demographics and conventional echo-Doppler measurements

Patients' demographic characteristics were similar to normal controls (Table I). Conventional echocardiography demonstrated larger systolic and diastolic LV dimensions and LV hypertrophy at baseline in AS compared to controls. Both groups had normal LVEF. Left atrial (LA) size was similar in both groups. Estimated right ventricular systolic pressure was higher in patients with AS. Severe AS was demonstrated in all patients with a mean aortic valve area indexed for body surface area of 0.4 ± 0.1

Longitudinal and circumferential mechanics of severe AS

Myocardial systolic function is usually assessed by LVEF. Although this is clinically useful in patients with AS, symptoms start when ejection fraction (EF) is still normal. An abnormal EF is a late consequence and likely represents failure of compensatory mechanisms. Newer quantitative techniques such as speckle tracking myocardial mechanics evaluating strain, SR, and twist have been used to better characterize regional and global myocardial systolic and diastolic function and detect subtle

Conclusions

Patients with severe AS undergoing AVR provide a clinical model of the effects of afterload on LV function. The LV compensates by increased apical rotation as well as changing the strain vector of systolic function, maintaining its magnitude by increased circumferential strain compensating for decreased longitudinal strain. After AVR and relief of afterload, there is a gradual improvement in mechanics and resolution of compensatory mechanisms. Abnormal apical mechanics may be a key to the

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Septic cardiomyopathy is associated with poor outcomes but its definition remains unclear. In a previous meta-analysis, left ventricular (LV) longitudinal strain (LS) showed significant prognostic value in septic patients, but findings were not robust due to a limited number of studies, differences in effect size and no adjustment for confounders.
We conducted an updated systematic review (PubMed and Scopus up to 14.02.2023) and meta-analysis to investigate the association between LS and survival in septic patients. We included studies reporting global (from three apical views) or regional LS (one or two apical windows). A secondary analysis evaluated the association between LV ejection fraction (EF) and survival using data from the selected studies.
We included fourteen studies (1678 patients, survival 69.6%) and demonstrated an association between better performance (more negative LS) and survival with a mean difference (MD) of −1.45%[−2.10, −0.80] (p < 0.0001;I² = 42%). No subgroup differences were found stratifying studies according to number of views used to calculate LS (p = 0.31;I² = 16%), severity of sepsis (p = 0.42;I² = 0%), and sepsis criteria (p = 0.59;I² = 0%). Trial sequential analysis and sensitivity analyses confirmed the primary findings. Grade of evidence was low. In the included studies, thirteen reported LVEF and we found an association between higher LVEF and survival (MD = 2.44% [0.44,4.45]; p = 0.02;I² = 42%).
We confirmed that more negative LS values are associated with higher survival in septic patients. The clinical relevance of this difference and whether the use of LS may improve understanding of septic cardiomyopathy and prognostication deserve further investigation. The association found between LVEF and survival is of unlikely clinical meaning.
PROSPERO number CRD42023432354
Relevance of Functional Mitral Regurgitation in Aortic Valve Stenosis
2020, American Journal of Cardiology
The clinical relevance of functional-mitral-regurgitation (FMR) in patients with aortic valve stenosis (AS) has been poorly studied using a quantitative approach. In addition, FMR prognostic value has mostly been analyzed after aortic valve replacement. Between 2010 and 2014 the echocardiograms of consecutive AS patients were retrospectively reviewed. Inclusion criteria were calcified aortic valve with transaortic-velocity >2.5 m/s and calculated mitral effective regurgitant orifice area (ERO) in the presence of mitral regurgitation. Organic mitral valve disease was an exclusion-criteria. Primary endpoint was heart failure or death under medical management. Secondary endpoint was heart failure or death. Eligible patients were 189, age 79 ± 8 years, 61% NYHA I/II, indexed aortic valve area (AVA) 0.55 ± 0.17 cm²/m². Mitral ERO was 7.6 ± 4.2 mm² (>10 mm² in 30% of patients). Longitudinal function (by S’-TDI) was associated with mitral ERO independently of ejection fraction and ventricular volumes (p = 0.01). Mitral ERO greater than 10 mm² (threshold identified by spline survival-modeling) was associated with severe symptoms (Odds ratio [OR] 3.1 [1.6 to 6.0]; p = 0.0006) and higher pulmonary-arterial-pressure (OR 3.0 [1.4 to 5.9]; p = 0.002). Follow-up was completed for 175 patients. After 4.7 [1.4 to 7.2] years, 87 (50%) patients underwent AVR, 66 (38%) had heart-failure, 64 (37%) died. No procedure on FMR was required. Mitral ERO was independently associated with primary and secondary endpoints both as continuous variable (Hazard ratio [HR] 1.15 [1.00 to 1.30]; p = 0.04 and HR 1.23 [1.05 to 1.43]; p = 0.01 per 5 mm² ERO increase) or as ERO> versus ≤10 mm². Adjustment for S’-TDI or subgroup-analysis did not affect results. The analysis by AVA revealed the incremental prognostic role of mitral ERO over AS severity. In conclusion, AS patients with concomitant FMR >10 mm² holds a higher risk during medical follow-up. FMR quantitation, even for volumetrically modest regurgitation, provides incremental prognostic information over AS severity.
Relative Contribution of Afterload and Interstitial Fibrosis to Myocardial Function in Severe Aortic Stenosis
2020, JACC: Cardiovascular Imaging
The present study aimed at investigating the respective contribution of afterload and myocardial fibrosis to pre- and post-operative left ventricular (LV) function by using stress−strain relationships.
Separating the effect of myocardial dysfunction and afterload on pump performance has important implications for the prognosis and management of patients with severe aortic stenosis (AS).
A total of 101 patients with isolated severe AS (57% men; mean age 71 years) and 75 healthy control subjects underwent resting 2-dimensional and speckle-tracking echocardiography to measure global circumferential strain (GCS) and global longitudinal strain (GLS), as well as end-systolic wall stress (ESWS). Normal stress−strain relationships were constructed using control subjects’ data and fitted to linear regression. End-systolic stress−strain indexes (the number of SDs from the mean regression line) were used as an afterload-independent index of myocardial function and compared with myocardial fibrosis, measured on transmural myocardial biopsies harvested at the time of surgery.
GCS and GLS were afterload-dependent in both control subjects and patients. The GLS-ESWS relationship of patients was shifted downward compared with control subjects. Patients with reduced pre-operative end-systolic stress−strain indexes exhibited larger degrees of interstitial myocardial fibrosis than patients without (3.8 ± 2.9% vs. 8.3 ± 6.3%, p < 0.001; and 4.9 ± 4.4% vs. 9.5 ± 6.4%; p < 0.001, for GLS and GCS, respectively). By multivariate analysis, pre-operative end-systolic stress−strain indexes were the only predictors of post-operative longitudinal and circumferential end-systolic stress−strain indexes (ß = 0.49 and ß = 0.60, respectively; p < 0.001).
Myocardial strains are afterload-dependent. In patients with severe AS, pre-operative stress−strain indexes allow identification of patients with increased myocardial fibrosis and predict the extent of functional recovery after aortic valve replacement.
Use of “speckle tracking” in non-cancer patients
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La evaluación de la función sistólica es fundamental para la toma de decisiones clínicas en cardiología. Los métodos actuales basados el cálculo de la Fracción de Eyección Ventricular Izquierda como parámetro de la función sistólica, se soportan en medidas volumétricas. Con el advenimiento de la ecocardiografía speckle tracking, se puede determinar el grado de deformación de la fibra miocárdica (Strain) y obtener una medida más directa de la función sistólica, lo cual ha despertado un interés creciente sobre su utilidad en la práctica clínica. Por tanto, en esta revisión se presenta evidencia actualizada sobre la aplicación de la ecocardiografía speckle tracking, en diferentes cardiopatías de origen no oncológico. Por ejemplo, el Strain Longitudinal Global, el parámetro mejor estudiado de la ecocardiografía speckle tracking, provee información pronóstica en enfermedades como la cardiomiopatía hipertrófica y cardiopatía isquémica. Un Strain Longitudinal Global alterado confiere un mayor riesgo de eventos cardiovasculares en pacientes con valvulopatías aórticas y mitral; incluso con Fracción de Eyección Ventricular Izquierda preservada, lo cual abre la posibilidad de anticipar el tiempo de intervención quirúrgica. La ecocardiografía speckle tracking, también permite cuantificar el strain auricular izquierdo, permitiendo evaluar con mayor precisión la función diastólica. Aunque para cada cardiopatía se presentan valores de referencia de Strain, esta técnica aún se encuentra en desarrollo; por tanto, aún no hay valores de corte estandarizados dado la amplia variabilidad inter-proveedores. Sin embargo, por los avances diarios en la técnica de ecocardiografía speckle tracking, se espera que su uso rutinario sea considerado en las guías de práctica clínica futuras como herramienta de decisión clínica.
The evaluation of systolic function is fundamental for clinical decision making in cardiology. The current methods based on the calculation of the Left Ventricular Ejection Fraction (LVEF) as a parameter of the systolic function are supported in volumetric measurements. With the advent of speckle tracking echocardiography (STE), the degree of deformation of the myocardial fiber (Strain) can be determined and a more direct measure of systolic function can be obtained, which has aroused a growing interest in its usefulness in clinical practice. Therefore, this review presents updated evidence on the application of STE in different heart diseases of non-oncological origin. For example, the Global Longitudinal Strain (GLS), the best-studied parameter of STE, provides prognostic information in diseases such as hypertrophic cardiomyopathy and ischemic heart disease. An altered GLS confers an increased risk of cardiovascular events in patients with aortic and mitral valve disease; even with preserved LVEF, which opens the possibility of anticipating the time of surgical intervention. The STE also allows the quantification of left atrial strain, allowing a more accurate assessment of diastolic function. Although reference values of Strain are presented for each cardiopathy, this technique is still in development; therefore, there are still no standardized cut-off values given the wide inter-vendor variability. However, due to the daily advances in the STE technique, it is expected that its routine use will be considered in future clinical practice guidelines as a clinical decision tool.
Alterations in Layer-Specific Left Ventricular Global Longitudinal and Circumferential Strain in Patients With Aortic Stenosis: A Comparison of Aortic Valve Replacement versus Conservative Management Over a 12-Month Period
2019, Journal of the American Society of Echocardiography
Impairment in left ventricular (LV) systolic strain in aortic stenosis (AS) is well documented. However, alterations in layer-specific LV global longitudinal strain (GLS) and global circumferential strain (GCS) and their recovery following surgical aortic valve replacement (AVR) have not been established. The aim of this study was to examine layer-specific changes in GLS and GCS in patients with AS undergoing AVR and compare these patients with those managed conservatively over 12 months.
Eighty-six patients (mean age, 68.8 ± 12 years; 60 men) with AS (19 mild, 15 moderate, and 52 severe) were prospectively recruited. Patients with coronary disease or other significant valvular disease were excluded. Forty patients (46.5%) with severe AS underwent AVR. All patients underwent baseline echocardiography. Patients managed conservatively underwent follow-up echocardiography at 12 months. Patients undergoing AVR underwent follow-up echocardiography at 1 week and 3, 6, and 12 months after AVR.
There was worsening in subendocardial but not subepicardial or transmural GLS even in mild AS (−20.9 ± 1.0% vs −20.6 ± 0.8%, P = .012). In moderate AS, worsening in subendocardial (−19.6 ± 0.9% vs −18.2 ± 1.5%, P = .003), subepicardial (−14.9 ± 1.0% vs −13.8 ± 1.2%, P = .004), and transmural (−17.1 ± 0.9% vs −15.8 ± 1.3%, P = .03) GLS and a trend toward significant worsening in subendocardial GCS (−29.8 ± 5.16% vs −27.5 ± 5%, P = .054) were seen. Conservatively managed patients with severe AS had significant worsening in subendocardial (−16.1 ± 1.6% vs −13.9 ± 2.6%, P = .021), subepicardial (−11.6 ± 1.1% vs −10.1 ± 2.1%, P = .027), and transmural (−13.6 ± 1.3% vs −11.8 ± 2.3%, P = .02) GLS and subendocardial (−24.9 ± 3.6% vs −20.8 ± 4.5%, P = .002) and transmural (−16.9 ± 1.7% vs −14.3 ± 3.5%, P = .04) GCS on follow-up. Patients after AVR demonstrated significant improvement in GLS (from 3 months) and GCS (from 6 months) in both myocardial layers.
Patients with AS managed conservatively had worsening of GLS over 12 months despite preserved LV ejection fraction, detected earliest in the subendocardial layer. GCS became progressively impaired in moderate and severe AS. Improvement in LV strain after AVR was seen earlier with GLS (from 3 months) than with GCS (from 6 months) in both myocardial layers.
Differential Myocardial Fibre Involvement by Strain Analysis in Patients With Aortic Stenosis
2018, Heart Lung and Circulation
Citation Excerpt :
In contrast, LV strain and strain rate analysis are more sensitive indices of subclinical myocardial involvement. Recent studies have shown abnormal LV strain mechanics despite preserved LVEF in patients with AS [3,4]. Myocardial architecture is a complex array of longitudinally and circumferentially orientated fibres, predominantly organised in subendocardial and subepicardial layers, respectively [5].
Aortic stenosis (AS) is the most common valvular heart disease and can result in left ventricular (LV) systolic impairment. LV myocardial fibres are organised in layers: the subendocardial layer is orientated longitudinally and the subepicardial layer circumferentially. We hypothesised that there is differential involvement of myocardial fibres in patients with aortic stenosis.
We performed multi-directional, multi-layered systolic strain analysis in 70 patients (aged 72 ± 10.7 years) with varying grades of AS severity (mean gradient 32.3 ± 20 mmHg, aortic valve area 1.1 ± 0.6 cm²) and in 30 controls. Clinical, demographic and resting echocardiographic data were recorded. Left ventricular subendocardial and subepicardial systolic strains were measured in the longitudinal, radial and circumferential axes.
Systolic subendocardial strain was significantly higher than subepicardial strain in all three axes in patients and in controls. There were significant differences in longitudinal, but not in circumferential and radial strain, or left ventricular ejection fraction (LVEF), between patient groups. Aortic valve mean gradient (MG) and valve area (AVA) correlated better with subendocardial longitudinal strain (r = 0.548, p < 0.001; r = −0.54, p < 0.001 respectively) than with subepicardial longitudinal strain (r = 0.496, p < 0.001, r = −0.544, p < 0.001 respectively). Correlations between circumferential and radial strain and MG or AVA were poor.
There was differential impairment in LV systolic strain in all three cardiac axes in patients with AS. Left ventricular longitudinal strain impairment was proportional to AS severity. Subendocardial longitudinal strain correlated better with AS severity than subepicardial longitudinal strain while correlations between circumferential and radial strain and AS severity were weak.

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Clinical InvestigationValvular and Congenital Heart DiseaseDifferential effects of afterload on left ventricular long- and short-axis function: Insights from a clinical model of patients with aortic valve stenosis undergoing aortic valve replacement

Background

Methods

Results

Conclusions

Section snippets

Study population

Baseline demographics and conventional echo-Doppler measurements

Longitudinal and circumferential mechanics of severe AS

Conclusions

J Am Soc Echocardiogr

J Am Soc Echocardiogr

J Am Soc Echocardiogr.

J Am Soc Echocardiogr

J Am Soc Echocardiogr

J Am Coll Cardiol

J Am Soc Echocardiogr

J Am Soc Echocardiogr

J Am Soc Echocardiogr.

J Am Soc Echocardiogr

J Am Soc Echocardiogr

Clinical Investigation
Valvular and Congenital Heart Disease
Differential effects of afterload on left ventricular long- and short-axis function: Insights from a clinical model of patients with aortic valve stenosis undergoing aortic valve replacement