© 2014, Wiley Periodicals, Inc. DOI: 10.1111/echo.12825
Echocardiography
Combined Circumferential and Longitudinal Left Ventricular Systolic Dysfunction in Patients with Asymptomatic Aortic Stenosis Giovanni Cioffi, M.D.,* Carmine Mazzone, M.D.,† Giulia Barbati, Ph.D.,† Andrea Rossi, M.D.,‡ Stefano Nistri, M.D.,§ Federica Ognibeni,* Luigi Tarantini, M.D.,¶ Andrea Di Lenarda, M.D.,† Pompilio Faggiano, M.D.,** Giovanni Pulignano, M.D.,†† Carlo Stefenelli, M.D.,* Giovanni de Simone, M.D.,‡‡ and Richard B. Devereux, M.D.§§ *Department of Cardiology, Villa Bianca Hospital, Trento, Italy; †Cardiovascular Center, Trieste and University of Trieste, Trieste, Italy; ‡Division of Cardiology, Department of Medicine, University and Public Hospital, Verona, Italy; §Cardiology Service, CMSR Veneto Medical Center, Vicenza, Italy; ¶Department of Cardiology, S. Martino Hospital, Belluno, Italy; **Cardiology Unit, “Spedali Civili” Hospital, Brescia, Italy; ††Heart Failure Clinic, Division of Cardiology/C.C.U., San Camillo Hospital, Rome, Italy; ‡‡Department of Translational Medical Sciences, Federico II, University Hospital, School of Medicine, Naples, Italy; and §§Greenberg Division of Cardiology, Weill Cornell Medical College, New York, New York
Background: Early detection of left ventricular (LV) systolic dysfunction is pivotal in the management of patients with aortic stenosis (AS). LV circumferential and/or longitudinal shortening may be impaired in these patients despite LV ejection fraction is preserved. We focused on prevalence and factors associated with combined impairment of circumferential and longitudinal shortening (C&L) in asymptomatic AS patients. Methods: Echocardiographic and clinical data from 200 patients with asymptomatic AS of any degree without history of heart failure and normal LV ejection fraction were analyzed. C&L were evaluated by mid-wall shortening (MS) and tissue Doppler mitral annular peak systolic velocity (S’), and classified low if 50% and normal LV wall motion were required for inclusion in the study. Exclusion criteria were: history of heart failure, previous myocardial infarction or diagnosis of coronary artery disease (by clinical, electrocardiographic, and echocardiographic evaluation at rest and by the results of exercise/echo stress test) including any indication to coronary angiography and/or prior myocardial revascularization, prevalent atrial fibrillation, more than mild mitral valve regurgitation or stenosis, primary dilated or hypertrophic or restrictive cardiomyopathy, severe chronic obstructive pulmonary disease, any neoplastic disease. Eligible patients were prospectively studied between January 2010 and December 2012. Clinical evaluation including history (presence of hypertension, diabetes, obesity, dyslipidemia, active smoking), physical examination and routine laboratory tests were performed in all subjects within 2 weeks from echocardiography. All subjects with AS were “asymptomatic,” a status recognized in patients in New York Heart Association (NYHA) functional class I without angina or syncope. All gave written informed consent and the study was approved by Ethical Committees in both participating Centers. The study complies with the Declaration of Helsinki. A group of 100 normotensive healthy volunteers was also selected to assess the range of normal values of C&L shortening, for categorical definition of C&L dysfunction (for details see the “Echocardiography” section). These subjects were statistically comparable with those enrolled into the study for age, sex, and body mass index according to the following procedure: a Gower’s generalized distance from each of the healthy control was computed and ranked in ascending order. The distance was calculated using these variables ordered as follows: age, gender, body mass index. The 100 healthy controls and 200 AS patients were then defined by taking for every
two close patients with AS the closest control (selected by a pool of 170 patients). Definitions: Concomitant hypertension was defined as systolic blood pressure of ≥140 mmHg and/or a diastolic blood pressure of ≥90 mmHg and/or use of antihypertensive therapy. Obesity was defined as body mass index ≥30 kg/m2. Dyslipidemia was defined as total serum cholesterol >190 mg/ dL and or triglycerides >150 mg/dL or use of lipid-lowering therapy. To assess renal function glomerular filtration rate was estimated by the simplified MDRD equation. Echocardiography: Standard transthoracic Doppler echocardiography studies were performed using an Alpha Esaote Biomedica machine (Florence, Italy) equipped with a 2.5-3.5 MHz annular-array transducer. Images were stored on CD or MO disks and forwarded for final interpretation at the Echocardiography Core Laboratory at Villa Bianca Hospital of Trento, Italy. Echocardiographers were blind to clinical information. LV chamber dimensions and wall thickness were measured according to the American Society of Echocardiography recommendations and LV mass calculated using a necropsy validated formula.14 LV mass was normalized for height to the 2.7 power and LV hypertrophy was defined as LV mass ≥49.2 g/m2.7 for men and ≥46.7 for women.15 Excess of LV mass was assessed as the ratio between observed and predicted values of LV mass, as previously reported.16 Relative wall thickness was calculated as the ratio of posterior wall thickness to LV radius and was indicative of concentric LV geometry if ≥0.43.17 LV end-diastolic and end-systolic volumes and stroke volume were measured by the biplane method of disks from 2D apical four-chamber plus twochamber views and used to calculate ejection fraction and cardiac index. Circumferential LV systolic function was assessed at the mid-wall level.18 Mid-wall shortening (MS) 4 m per second.
The degree of valve calcification was scored according to the following criteria: 0 = no calcification, 1 = mildly calcified (isolated, small spots), 2 = moderately calcified (multiple bigger spots), 3 = heavily calcified (extensive thickening/calcification of all cusps).24 The CAIMAN-ECHO score was computed for a prognostic estimation in each patient.25 Three echocardiographic variables were the bricks of the CAIMAN-ECHO score: based on the hazard ratios of Cox analysis, the score was calculated as follows: calcium score of the aortic valve 1–3 = 1 point, 4 = 6 points; transvalvular peak jet velocity ≤3.6 m/sec = 1 point, >3.6 m/sec = 3 points, observed/predicted LV mass ratio ≤110% = 1 point, >110% = 3 points. The score ranged from 3 (whereas the values of all variables were under each prognostic cutoff) to 12 points (whereas the values of all variables were over the prognostic cutoff used in this study). The score generated several levels of risk which reflected the number of the predictors detected to the echocardiographic evaluation. The outcome significantly changed between patients with a score of 3 or 5 points and those with 7 points or more, with a difference in event rate which was about threefold higher in the latter than in the former. The accuracy of the score in predicting events was 84% and 77% (P = 0.09) in the original and validation cohort, respectively. 1066
Global LV load was assessed by the valvuloarterial impedance as proposed by Briand et al.26 taking into account the net mean transaortic gradient and thus the phenomenon of pressure recovery downstream to the stenotic valve27: Valvulo-arterial impedance = (Systolic arterial pressure x Mean net transaortic gradient)/ (Stroke volume/body surface area). Statistical Analysis: Data are reported as mean values 1 SD. SPSS 19.0 Release (SPSS Inc., Chicago, IL, USA) has been used for statistical analysis. Between-group comparisons of categorical and continuous variables were performed by v2 test and analysis of variance (ANOVA) with comparison among groups by Scheffe test and Tukey HSD (Spjøtvoll/ Stoline) test for unequal sample, as appropriate. Multivariable analysis (logistic regression, enter method) was computed to identify the factors independently related to combined C&L dysfunction. We included in the final model the following variables, selected on the basis of exploratory statistics: age, sex, LV mass index, concentric LV geometry, E/e’ ratio, aortic valve area, degree of AS (as mild, moderate or severe), energy loss index, aortic valve calcium score (0–3 points). Curve fitting estimation was performed to investigate the relations between circumferential and longitudinal shortening. The possible relationships considered were: linear, quadratic, cubic, compound, growth, logarithmic, exponential, inverse, power, and logistic. They were applied on the total population and on the subgroups of patients with and without combined C&L dysfunction. To determine which model to use, we viewed the scatterplots of our data, analyzed the type of mathematical function, and transformed our data fitting to the corresponding type of available model. Thus, we considered the significance value of the F statistic (less than 0.05 indicated that the variation explained by each model was not due to chance). The r2 coefficient was used as indicator of goodness of fit for each model. The statistical difference between models was measured by analysis of variance (ANOVA). A 2-tailed value of P < 0.05 was considered statistically significant. Results: The study population consisted of 200 patients with AS whose main clinical and echocardiographic characteristics are shown in Tables I and II, respectively. Most patients had an AS of mildto-moderate degree and only one-fourth had a
Systolic Dysfunction in Aortic Stenosis
TABLE I Main Clinical Characteristics of the 200 Study Patients Divided According to the Presence of Combined Circumferential and Longitudinal Left Ventricular Dysfunction
Variables Clinical Age (years) Female gender (%) Body surface area (m2) Body mass index (Kg/m2) Obesity (%) Hypertension (%) Duration of hypertension (years) Dyslipidemia (%) Active smoker, % Diabetes (%) Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg) Pulse pressure (mmHg) Heart rate (beats/minute) Laboratory Hemoglobin (g/dL) Creatinine (mg/dL) GFR (mL/min/1.73 m2) Total cholesterol (mg/dL) Cholesterol LDL (mg/dL) Triglycerides (mg/dL) Pharmacological treatment b-blockers (%) ACEi/ARB (%) Diuretics (%) Calcium antagonists (%) Antihypertension medications* Antiplatelets agents (%) Statins (%)
Combined Dysfunction NO (128 Patients)
Combined Dysfunction YES (72 Patients)
P
Total Study Population (200 Patients)
76 10 52 1.81 0.21 27.0 5.4 25 64 7 (3–13) 31 10 9 142 18 79 8 63 16 70 10
78 8 58 1.82 0.22 27.6 4.8 30 66 8 (2–15) 42 5 13 139 20 79 9 60 20 70 8
0.15 0.39 0.81 0.48 0.42 0.77 0.62 0.12 0.27 0.61 0.36 0.92 0.70 0.92
76 10 54 1.81 0.21 27.2 5.2 27 64 7 (2–12) 35 8 11 141 19 79 10 62 17 70 10
13.2 1.9 1.1 0.5 60 29 184 (171–211) 100 (84–122) 125 (99–188)
13.7 1.9 1.1 0.5 66 35 186 (167–221) 104 (85–127) 127 (99–170)
0.33 0.81 0.45 0.65 0.55 0.78
13.4 1.9 1.1 0.5 62 31 184 (162–219) 101 (85–127) 126 (97–172)
23 56 31 15 1.3 1.2 27 22
31 52 38 26 1.5 1.2 33 30
0.33 0.69 0.36 0.07 0.31 0.38 0.21
26 55 34 19 1.4 1.2 30 25
*Number per patient. ACEi = angiotensin-converting enzyme inhibitors; ARB = angiotensin T1 receptor blockers; GFR = glomerular filtration rate.
severe asymptomatic AS. Both C&L function was normal in 42 patients (21%). Circumferential dysfunction was detected in 106 patients (53%), longitudinal dysfunction in 124 (62%). Combined C&L dysfunction coexisted in 72 patients (36% of the total study population). These patients had clinical and laboratory characteristics comparable to those without C&L dysfunction, and similar pharmacological treatment. In contrast, echocardiographic characteristics differed substantially. Patients with C&L dysfunction had smaller aortic valve area and higher transvalvular peak gradient, increased LV mass, higher prevalence of aortic valve calcium, more severe LV diastolic dysfunction and LV concentric geometry than those without combined C&L fibers dysfunction. More specifically, C&L dysfunction was found in 63 of 142 patients (44%) with concentric LV geometry and in 9 of 58 patients (16%) with eccentric LV geometry
(P < 0.001). No difference in LV ejection fraction was found between the two study groups. Of note, patients with C&L dysfunction exhibited a CAIMAN prognostic score significantly worse than those without combined C&L dysfunction (8.4 3.1 vs. 6.4 2.9 points, respectively; P < 0.001) (Fig. 1). A logistic regression analysis was performed to find the independent variables associated with C&L dysfunction. The statistical model indicated 3 covariates: higher LV mass (OR 1.02 [CI 1.01– 1.04], P = 0.03), E/e’ ratio (OR 1.11 [CI 1.04– 1.19], P = 0.001) and concentric LV geometry (OR 4.30 [CI 1.79–10.34], P = 0.001). Degree of AS and aortic calcium score were not associated with combined C&L dysfunction. Based on these data, we analyzed the prevalence of combined C&L dysfunction in patients selected according to the presence/absence of LV concentric geometry and/or LV diastolic 1067
Cioffi, et al.
TABLE II Echocardiographic Characteristics
Variables Aortic valve structure and function Peak aortic transvalvular velocity (mmHg) Aortic transvalvular PG (mmHg) Aortic transvalvular MG (mmHg) Aortic valve area index (cm2/m2) Degree of aortic stenosis (%) Mild Moderate Severe Energy loss index (cm²/m²) Valvulo-arterial impedance (mmHg/mLm2) Aortic valve regurgitation (%)* Aortic valve calcium (score 0–3) “CAIMAN” prognostic score (points) Left ventricular structure and function LV EDD (cm/m2) LV ESD (cm/m2) LV EDV (mL/m2) LV ESV (mL/m2) Relative wall thickness Concentric LV geometry (%) LV mass index (g/m2.7) LV hypertrophy (%) Observed/predicted LV mass (%) LV stroke volume (mL/m2) Cardiac index (L/min/m2) LV ejection fraction (%) LV CESS (dynes/cm2) LV mid-wall shortening (%) Low LV mid-wall shortening (%) Peak S’ (cm/sec) Low peak S’ (%) Peak E’ (cm/sec) E-wave of transmitral flow (cm/sec) A-wave of transmitral flow (cm/sec) E/A ratio E/E’ ratio LV diastolic dysfunction (%) Grade I Grade II Grade III Maximal left atrial volume (mL/m2)
Combined Dysfunction NO (128 Patients)
Combined Dysfunction YES (72 Patients)
P
Total Study Population (200 Patients)
3.3 0.6 44 18 31 14 0.60 0.14
3.5 0.7 53 21 35 15 0.52 0.18
0.008 0.006 0.07 0.001
3.4 0.7 47 19 32 14 0.57 0.16
43 35 22 0.83 0.26 5.35 2.00 10 2.2 0.64 6.4 2.9
25 42 33 0.70 0.30 5.05 1.87 9 2.4 0.65 8.4 3.1
0.01
36 38 26 0.78 0.27 5.16 1.90 10 2.3 0.65 7.2 3.1
2.8 0.4 1.6 0.3 49 13 18 6 0.45 0.09 62 54 15 64 123 33 31 9 2.2 0.7 64 6 126 46 17.6 3.0 34 (27%) 9.0 1.8 52 (41%) 8.6 2.3 75 25 89 23 0.86 0.34 9.2 3.6 39 36 2 1 25 10
2.6 0.3 1.7 0.4 46 16 17 8 0.57 0.16 87 65 21 82 180 54 29 9 2.0 0.7 63 7 130 2 13.3 2.7 72 (100%) 6.8 1.1 72 (100%) 6.5 1.9 75 27 96 25 0.83 0.39 12.6 5.5 68 56 8 4 27 8
0.002 0.28 0.88 0.03
Echocardiography
Combined Circumferential and Longitudinal Left Ventricular Systolic Dysfunction in Patients with Asymptomatic Aortic Stenosis Giovanni Cioffi, M.D.,* Carmine Mazzone, M.D.,† Giulia Barbati, Ph.D.,† Andrea Rossi, M.D.,‡ Stefano Nistri, M.D.,§ Federica Ognibeni,* Luigi Tarantini, M.D.,¶ Andrea Di Lenarda, M.D.,† Pompilio Faggiano, M.D.,** Giovanni Pulignano, M.D.,†† Carlo Stefenelli, M.D.,* Giovanni de Simone, M.D.,‡‡ and Richard B. Devereux, M.D.§§ *Department of Cardiology, Villa Bianca Hospital, Trento, Italy; †Cardiovascular Center, Trieste and University of Trieste, Trieste, Italy; ‡Division of Cardiology, Department of Medicine, University and Public Hospital, Verona, Italy; §Cardiology Service, CMSR Veneto Medical Center, Vicenza, Italy; ¶Department of Cardiology, S. Martino Hospital, Belluno, Italy; **Cardiology Unit, “Spedali Civili” Hospital, Brescia, Italy; ††Heart Failure Clinic, Division of Cardiology/C.C.U., San Camillo Hospital, Rome, Italy; ‡‡Department of Translational Medical Sciences, Federico II, University Hospital, School of Medicine, Naples, Italy; and §§Greenberg Division of Cardiology, Weill Cornell Medical College, New York, New York
Background: Early detection of left ventricular (LV) systolic dysfunction is pivotal in the management of patients with aortic stenosis (AS). LV circumferential and/or longitudinal shortening may be impaired in these patients despite LV ejection fraction is preserved. We focused on prevalence and factors associated with combined impairment of circumferential and longitudinal shortening (C&L) in asymptomatic AS patients. Methods: Echocardiographic and clinical data from 200 patients with asymptomatic AS of any degree without history of heart failure and normal LV ejection fraction were analyzed. C&L were evaluated by mid-wall shortening (MS) and tissue Doppler mitral annular peak systolic velocity (S’), and classified low if 50% and normal LV wall motion were required for inclusion in the study. Exclusion criteria were: history of heart failure, previous myocardial infarction or diagnosis of coronary artery disease (by clinical, electrocardiographic, and echocardiographic evaluation at rest and by the results of exercise/echo stress test) including any indication to coronary angiography and/or prior myocardial revascularization, prevalent atrial fibrillation, more than mild mitral valve regurgitation or stenosis, primary dilated or hypertrophic or restrictive cardiomyopathy, severe chronic obstructive pulmonary disease, any neoplastic disease. Eligible patients were prospectively studied between January 2010 and December 2012. Clinical evaluation including history (presence of hypertension, diabetes, obesity, dyslipidemia, active smoking), physical examination and routine laboratory tests were performed in all subjects within 2 weeks from echocardiography. All subjects with AS were “asymptomatic,” a status recognized in patients in New York Heart Association (NYHA) functional class I without angina or syncope. All gave written informed consent and the study was approved by Ethical Committees in both participating Centers. The study complies with the Declaration of Helsinki. A group of 100 normotensive healthy volunteers was also selected to assess the range of normal values of C&L shortening, for categorical definition of C&L dysfunction (for details see the “Echocardiography” section). These subjects were statistically comparable with those enrolled into the study for age, sex, and body mass index according to the following procedure: a Gower’s generalized distance from each of the healthy control was computed and ranked in ascending order. The distance was calculated using these variables ordered as follows: age, gender, body mass index. The 100 healthy controls and 200 AS patients were then defined by taking for every
two close patients with AS the closest control (selected by a pool of 170 patients). Definitions: Concomitant hypertension was defined as systolic blood pressure of ≥140 mmHg and/or a diastolic blood pressure of ≥90 mmHg and/or use of antihypertensive therapy. Obesity was defined as body mass index ≥30 kg/m2. Dyslipidemia was defined as total serum cholesterol >190 mg/ dL and or triglycerides >150 mg/dL or use of lipid-lowering therapy. To assess renal function glomerular filtration rate was estimated by the simplified MDRD equation. Echocardiography: Standard transthoracic Doppler echocardiography studies were performed using an Alpha Esaote Biomedica machine (Florence, Italy) equipped with a 2.5-3.5 MHz annular-array transducer. Images were stored on CD or MO disks and forwarded for final interpretation at the Echocardiography Core Laboratory at Villa Bianca Hospital of Trento, Italy. Echocardiographers were blind to clinical information. LV chamber dimensions and wall thickness were measured according to the American Society of Echocardiography recommendations and LV mass calculated using a necropsy validated formula.14 LV mass was normalized for height to the 2.7 power and LV hypertrophy was defined as LV mass ≥49.2 g/m2.7 for men and ≥46.7 for women.15 Excess of LV mass was assessed as the ratio between observed and predicted values of LV mass, as previously reported.16 Relative wall thickness was calculated as the ratio of posterior wall thickness to LV radius and was indicative of concentric LV geometry if ≥0.43.17 LV end-diastolic and end-systolic volumes and stroke volume were measured by the biplane method of disks from 2D apical four-chamber plus twochamber views and used to calculate ejection fraction and cardiac index. Circumferential LV systolic function was assessed at the mid-wall level.18 Mid-wall shortening (MS) 4 m per second.
The degree of valve calcification was scored according to the following criteria: 0 = no calcification, 1 = mildly calcified (isolated, small spots), 2 = moderately calcified (multiple bigger spots), 3 = heavily calcified (extensive thickening/calcification of all cusps).24 The CAIMAN-ECHO score was computed for a prognostic estimation in each patient.25 Three echocardiographic variables were the bricks of the CAIMAN-ECHO score: based on the hazard ratios of Cox analysis, the score was calculated as follows: calcium score of the aortic valve 1–3 = 1 point, 4 = 6 points; transvalvular peak jet velocity ≤3.6 m/sec = 1 point, >3.6 m/sec = 3 points, observed/predicted LV mass ratio ≤110% = 1 point, >110% = 3 points. The score ranged from 3 (whereas the values of all variables were under each prognostic cutoff) to 12 points (whereas the values of all variables were over the prognostic cutoff used in this study). The score generated several levels of risk which reflected the number of the predictors detected to the echocardiographic evaluation. The outcome significantly changed between patients with a score of 3 or 5 points and those with 7 points or more, with a difference in event rate which was about threefold higher in the latter than in the former. The accuracy of the score in predicting events was 84% and 77% (P = 0.09) in the original and validation cohort, respectively. 1066
Global LV load was assessed by the valvuloarterial impedance as proposed by Briand et al.26 taking into account the net mean transaortic gradient and thus the phenomenon of pressure recovery downstream to the stenotic valve27: Valvulo-arterial impedance = (Systolic arterial pressure x Mean net transaortic gradient)/ (Stroke volume/body surface area). Statistical Analysis: Data are reported as mean values 1 SD. SPSS 19.0 Release (SPSS Inc., Chicago, IL, USA) has been used for statistical analysis. Between-group comparisons of categorical and continuous variables were performed by v2 test and analysis of variance (ANOVA) with comparison among groups by Scheffe test and Tukey HSD (Spjøtvoll/ Stoline) test for unequal sample, as appropriate. Multivariable analysis (logistic regression, enter method) was computed to identify the factors independently related to combined C&L dysfunction. We included in the final model the following variables, selected on the basis of exploratory statistics: age, sex, LV mass index, concentric LV geometry, E/e’ ratio, aortic valve area, degree of AS (as mild, moderate or severe), energy loss index, aortic valve calcium score (0–3 points). Curve fitting estimation was performed to investigate the relations between circumferential and longitudinal shortening. The possible relationships considered were: linear, quadratic, cubic, compound, growth, logarithmic, exponential, inverse, power, and logistic. They were applied on the total population and on the subgroups of patients with and without combined C&L dysfunction. To determine which model to use, we viewed the scatterplots of our data, analyzed the type of mathematical function, and transformed our data fitting to the corresponding type of available model. Thus, we considered the significance value of the F statistic (less than 0.05 indicated that the variation explained by each model was not due to chance). The r2 coefficient was used as indicator of goodness of fit for each model. The statistical difference between models was measured by analysis of variance (ANOVA). A 2-tailed value of P < 0.05 was considered statistically significant. Results: The study population consisted of 200 patients with AS whose main clinical and echocardiographic characteristics are shown in Tables I and II, respectively. Most patients had an AS of mildto-moderate degree and only one-fourth had a
Systolic Dysfunction in Aortic Stenosis
TABLE I Main Clinical Characteristics of the 200 Study Patients Divided According to the Presence of Combined Circumferential and Longitudinal Left Ventricular Dysfunction
Variables Clinical Age (years) Female gender (%) Body surface area (m2) Body mass index (Kg/m2) Obesity (%) Hypertension (%) Duration of hypertension (years) Dyslipidemia (%) Active smoker, % Diabetes (%) Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg) Pulse pressure (mmHg) Heart rate (beats/minute) Laboratory Hemoglobin (g/dL) Creatinine (mg/dL) GFR (mL/min/1.73 m2) Total cholesterol (mg/dL) Cholesterol LDL (mg/dL) Triglycerides (mg/dL) Pharmacological treatment b-blockers (%) ACEi/ARB (%) Diuretics (%) Calcium antagonists (%) Antihypertension medications* Antiplatelets agents (%) Statins (%)
Combined Dysfunction NO (128 Patients)
Combined Dysfunction YES (72 Patients)
P
Total Study Population (200 Patients)
76 10 52 1.81 0.21 27.0 5.4 25 64 7 (3–13) 31 10 9 142 18 79 8 63 16 70 10
78 8 58 1.82 0.22 27.6 4.8 30 66 8 (2–15) 42 5 13 139 20 79 9 60 20 70 8
0.15 0.39 0.81 0.48 0.42 0.77 0.62 0.12 0.27 0.61 0.36 0.92 0.70 0.92
76 10 54 1.81 0.21 27.2 5.2 27 64 7 (2–12) 35 8 11 141 19 79 10 62 17 70 10
13.2 1.9 1.1 0.5 60 29 184 (171–211) 100 (84–122) 125 (99–188)
13.7 1.9 1.1 0.5 66 35 186 (167–221) 104 (85–127) 127 (99–170)
0.33 0.81 0.45 0.65 0.55 0.78
13.4 1.9 1.1 0.5 62 31 184 (162–219) 101 (85–127) 126 (97–172)
23 56 31 15 1.3 1.2 27 22
31 52 38 26 1.5 1.2 33 30
0.33 0.69 0.36 0.07 0.31 0.38 0.21
26 55 34 19 1.4 1.2 30 25
*Number per patient. ACEi = angiotensin-converting enzyme inhibitors; ARB = angiotensin T1 receptor blockers; GFR = glomerular filtration rate.
severe asymptomatic AS. Both C&L function was normal in 42 patients (21%). Circumferential dysfunction was detected in 106 patients (53%), longitudinal dysfunction in 124 (62%). Combined C&L dysfunction coexisted in 72 patients (36% of the total study population). These patients had clinical and laboratory characteristics comparable to those without C&L dysfunction, and similar pharmacological treatment. In contrast, echocardiographic characteristics differed substantially. Patients with C&L dysfunction had smaller aortic valve area and higher transvalvular peak gradient, increased LV mass, higher prevalence of aortic valve calcium, more severe LV diastolic dysfunction and LV concentric geometry than those without combined C&L fibers dysfunction. More specifically, C&L dysfunction was found in 63 of 142 patients (44%) with concentric LV geometry and in 9 of 58 patients (16%) with eccentric LV geometry
(P < 0.001). No difference in LV ejection fraction was found between the two study groups. Of note, patients with C&L dysfunction exhibited a CAIMAN prognostic score significantly worse than those without combined C&L dysfunction (8.4 3.1 vs. 6.4 2.9 points, respectively; P < 0.001) (Fig. 1). A logistic regression analysis was performed to find the independent variables associated with C&L dysfunction. The statistical model indicated 3 covariates: higher LV mass (OR 1.02 [CI 1.01– 1.04], P = 0.03), E/e’ ratio (OR 1.11 [CI 1.04– 1.19], P = 0.001) and concentric LV geometry (OR 4.30 [CI 1.79–10.34], P = 0.001). Degree of AS and aortic calcium score were not associated with combined C&L dysfunction. Based on these data, we analyzed the prevalence of combined C&L dysfunction in patients selected according to the presence/absence of LV concentric geometry and/or LV diastolic 1067
Cioffi, et al.
TABLE II Echocardiographic Characteristics
Variables Aortic valve structure and function Peak aortic transvalvular velocity (mmHg) Aortic transvalvular PG (mmHg) Aortic transvalvular MG (mmHg) Aortic valve area index (cm2/m2) Degree of aortic stenosis (%) Mild Moderate Severe Energy loss index (cm²/m²) Valvulo-arterial impedance (mmHg/mLm2) Aortic valve regurgitation (%)* Aortic valve calcium (score 0–3) “CAIMAN” prognostic score (points) Left ventricular structure and function LV EDD (cm/m2) LV ESD (cm/m2) LV EDV (mL/m2) LV ESV (mL/m2) Relative wall thickness Concentric LV geometry (%) LV mass index (g/m2.7) LV hypertrophy (%) Observed/predicted LV mass (%) LV stroke volume (mL/m2) Cardiac index (L/min/m2) LV ejection fraction (%) LV CESS (dynes/cm2) LV mid-wall shortening (%) Low LV mid-wall shortening (%) Peak S’ (cm/sec) Low peak S’ (%) Peak E’ (cm/sec) E-wave of transmitral flow (cm/sec) A-wave of transmitral flow (cm/sec) E/A ratio E/E’ ratio LV diastolic dysfunction (%) Grade I Grade II Grade III Maximal left atrial volume (mL/m2)
Combined Dysfunction NO (128 Patients)
Combined Dysfunction YES (72 Patients)
P
Total Study Population (200 Patients)
3.3 0.6 44 18 31 14 0.60 0.14
3.5 0.7 53 21 35 15 0.52 0.18
0.008 0.006 0.07 0.001
3.4 0.7 47 19 32 14 0.57 0.16
43 35 22 0.83 0.26 5.35 2.00 10 2.2 0.64 6.4 2.9
25 42 33 0.70 0.30 5.05 1.87 9 2.4 0.65 8.4 3.1
0.01
36 38 26 0.78 0.27 5.16 1.90 10 2.3 0.65 7.2 3.1
2.8 0.4 1.6 0.3 49 13 18 6 0.45 0.09 62 54 15 64 123 33 31 9 2.2 0.7 64 6 126 46 17.6 3.0 34 (27%) 9.0 1.8 52 (41%) 8.6 2.3 75 25 89 23 0.86 0.34 9.2 3.6 39 36 2 1 25 10
2.6 0.3 1.7 0.4 46 16 17 8 0.57 0.16 87 65 21 82 180 54 29 9 2.0 0.7 63 7 130 2 13.3 2.7 72 (100%) 6.8 1.1 72 (100%) 6.5 1.9 75 27 96 25 0.83 0.39 12.6 5.5 68 56 8 4 27 8
0.002 0.28 0.88 0.03
