Whether concentric left ventricular (LV) hypertrophy (LVH) is a common precursor to depressed LV ejection fraction (EF) in humans is uncertain. From 1992 through 1994, 555 patients at our institution underwent echocardiography and had LVH (posterior or septal wall thickness ≥1.3 cm or concentric LVH noted) and normal LVEF. Of these, 220 (40%) had a follow-up assessment of LVEF by December 2008. The duration of follow-up was classified as short (≤7.5 years) or long (>7.5 years) term. The primary outcome was the development of a qualitatively depressed LVEF (mildly, moderately, or severely depressed). After a median follow-up of 7.5 years, 20% of the patients with concentric LVH developed a low LVEF. A low LVEF developed in 13% of subjects without interval myocardial infarction (MI) and 50% of subjects with interval MI during short-term follow-up (p <0.005). A low LVEF developed in 20% of subjects without interval MI and 44% of subjects with interval MI during long-term follow-up (p = 0.01). Of the subjects who developed a reduced LVEF, the relative wall thickness (median 0.5, 25th to 75th percentile 0.4 to 0.6) at follow-up was consistent with a concentric, rather than eccentric, phenotype. In conclusion, in patients with concentric LVH, the transition from a normal LVEF to a low LVEF was relatively infrequent (20%) after long-term follow-up in the absence of interval MI and usually did not result in a change in the LV geometry from a concentric to an eccentric phenotype.
In the classic model of hypertensive heart disease, chronically elevated blood pressure often leads to concentric left ventricular (LV) hypertrophy (LVH), followed by LV dilation and systolic dysfunction manifesting as a reduced LV ejection fraction (EF). This transition from concentric LVH to LV failure with systolic dysfunction has been shown in animal models and in patients with aortic stenosis. However, no large, longitudinal studies of hypertensive patients with concentric LVH have demonstrated whether this transition occurs commonly in this population. In the Cardiovascular Health Study, an increased LV mass was a risk factor for the development of a low LVEF after 5 years; however, it was eccentric and not concentric LVH that was associated with this outcome. We previously reported that only 18% of 159 patients with concentric LVH and a normal LVEF in the Parkland Memorial Hospital echocardiography database developed a low LVEF after a median follow-up of approximately 4 years. To further characterize the transition from concentric LVH to reduced LVEF, we reanalyzed this echocardiographic cohort after a longer period of follow-up. We hypothesized that the transition from concentric LVH with a normal LVEF to a depressed LVEF would remain infrequent despite the longer follow-up.
Methods
The reports from transthoracic echocardiograms performed at Parkland Memorial Hospital in Dallas, Texas, from June 1992 to August 1994 were screened; all studies were obtained for clinical indications. Those patients >17 years of age with concentric LVH (defined as posterior or septal wall thickness measuring ≥1.3 cm or the presence of concentric LVH specifically noted in report) and normal LVEF were identified (n = 855). Technically limited studies (n = 140) and those patients with significant valvular disease (greater than mild aortic regurgitation, aortic stenosis, or mitral regurgitation), asymmetrical septal or posterior wall hypertrophy, complex congenital heart disease, or LV regional wall motion abnormalities were excluded. From the remaining 555 patients, we included 220 subjects (40%) who had a follow-up transthoracic echocardiogram (n = 210) or other assessment of LVEF such as a transesophageal echocardiogram (n = 6) or multigated acquisition scan (n = 4) performed ≥1 year after the index echocardiogram as of December 2008. The 3 most common indications for the index echocardiogram were to assess LV function or wall motion, to evaluate the valves or an audible murmur, or a history of heart failure. These 3 indications accounted for 65% of the obtained echocardiograms. The institutional review board of University of Texas Southwestern Medical Center approved the protocol, and informed consent was waived because the study was retrospective.
The patient demographic and clinical data were reabstracted through a comprehensive chart review, including the electrocardiographic, radiographic, and echocardiographic reports generated for clinical purposes. LV function was assessed qualitatively as normal or depressed (mildly, moderately, or severely, representing a LVEF of approximately 40% to 50%, 30% to 39%, and <30%, respectively), as previously described. The primary outcome variable was the development of a qualitatively depressed LVEF (mildly, moderately, or severely) on a follow-up assessment. We dichotomized the duration of follow-up at the median (7.5 years) and classified it as short (≤7.5 years) and long (>7.5 years) term. An interval myocardial infarction (MI) between the index and follow-up study was identified by clinical history from the chart review. We subsequently reviewed the available electrocardiograms and cardiac enzyme levels related to the MI. The location of the MI was determined by the electrocardiographic changes and, if performed, the culprit vessel on left heart catheterization. Diastolic parameters, such as the mitral filling pattern, were not routinely measured on the index echocardiogram. Chest x-rays and laboratory tests were included if they were obtained within the 6 months preceding the index echocardiogram. A composite measure of coronary artery disease was defined as either a history of MI, percutaneous coronary intervention, or coronary artery bypass surgery or the presence of epicardial coronary stenoses of ≥70% with coronary angiography. Using the hospital electronic coding system, we searched for all admissions to Parkland Memorial Hospital with a primary or secondary diagnosis of heart failure from 1992 to 2008. We determined the frequency of the heart failure admissions that occurred ≥1 year after the index echocardiogram among 3 groups: those who had an index echocardiogram but no follow-up study, those who had preserved LVEF on the follow-up echocardiogram, and those with a low LVEF on the follow-up echocardiogram.
The data are expressed as proportions, mean ± SD, or median (twenty-fifth to seventy-fifth percentiles). The differences in the characteristics between the patients who did or did not progress to a depressed LVEF were compared using Fisher’s exact test, Student’s t test with equal or unequal variances, or the Wilcoxon rank-sum test, as appropriate. The relative wall thickness was defined as [septal wall thickness + posterior wall thickness]/[LV end-diastolic dimension (LVEDD)]. Bonferroni’s adjustment was used to account for multiple comparisons. A multivariate logistic regression model was developed including the significant variables (p <0.05) on univariate analysis using SAS for Windows, release 9.2 (SAS Institute, Cary, North Carolina). Odds ratios were calculated for a SD change in the continuous measurements.
Results
After a median follow-up of 7.5 years, 45 (20%) of 220 patients with concentric LVH developed a low LVEF ( Figure 1 ). Of these 45 patients with a reduced LVEF, 20 (44%) had mildly, 18 (40%) moderately, and 7 (16%) severely reduced LVEF. The baseline ( Table 1 ) clinical and echocardiographic characteristics are listed stratified by whether there was progression to a low LVEF. Those who did versus did not progress to a reduced LVEF were more likely to have a history of coronary artery disease at baseline. In addition, those who developed a low LVEF had both a larger LVEDD and LV end-systolic dimension and a smaller relative wall thickness on the index echocardiogram.
| Variable | Progression to Reduced LVEF | p Value | |
|---|---|---|---|
| No (n = 175) | Yes (n = 45) | ||
| Age (years) | 54 ± 12 | 55 ± 15 | 0.6 |
| Women | 67% | 51% | 0.06 |
| African American | 80% | 76% | 0.5 |
| Diabetes mellitus | 41% | 51% | 0.2 |
| Hypertension | 83% | 80% | 0.7 |
| Coronary artery disease ⁎ | 18% | 42% | 0.001 |
| Coronary artery bypass grafting | 5% | 16% | 0.02 |
| Cerebrovascular accident | 16% | 16% | 1 |
| Systolic blood pressure (mm Hg) (n = 163) | 153 ± 28 | 144 ± 21 | 0.09 |
| Diastolic blood pressure (mm Hg) (n = 163) | 87 ± 16 | 85 ± 16 | 0.6 |
| Heart rate (beats/min) | 80 (72–90) | 84.5 (71–92) | 0.6 |
| Medications (n = 158) | |||
| Angiotensin converting enzyme inhibitors | 31% | 38% | 0.4 |
| β Blockers | 18% | 21% | 0.8 |
| Diuretics | 35% | 41% | 0.6 |
| Serum creatinine (mg/dl) (n = 115) | 1 (0.8–1.2) | 1.1 (0.9–1.2) | 0.1 |
| Hemodialysis | 11% | 16% | 0.5 |
| Chest x-ray findings (n = 75) | |||
| Pulmonary edema | 38% | 47% | 0.6 |
| Cardiomegaly | 33% | 47% | 0.4 |
| Electrocardiographic findings | |||
| Left ventricular hypertrophy (n = 95) | 29% | 47% | 0.3 |
| Duration of QRS complex (ms) (n = 89) | 88 (80–98) | 88 (82–96) | 0.9 |
| Left ventricular strain pattern (n = 92) | 14% | 25% | 0.3 |
| Echocardiographic findings | |||
| Posterior wall thickness (cm) | 1.3 (1.3–1.5) | 1.3 (1.2–1.5) | 0.4 |
| Septal wall thickness (cm) | 1.4 (1.3–1.6) | 1.4 (1.3–1.5) | 0.5 |
| Left ventricular end-diastolic dimension (cm) | 4.1 ± 0.6 | 4.4 ± 0.6 | 0.01 |
| Left ventricular end-systolic dimension (cm) | 2.9 ± 0.5 | 3.1 ± 0.6 | 0.007 |
| Relative wall thickness | 0.7 (0.6–0.8) | 0.6 (0.6–0.7) | 0.02 |
⁎ Coronary artery disease defined as a history of myocardial infarction, percutaneous coronary intervention, or coronary artery bypass surgery or the presence of epicardial coronary stenoses of ≥70% on coronary angiography.
The follow-up clinical and echocardiographic characteristics are listed in Table 2 , again stratified by whether there was progression to a low LVEF. There was a more than threefold greater rate of interval MI in those who did versus did not develop a low LVEF. Of the 28 MIs, 18 of these patients were admitted to our institution and had cardiac enzyme measurements available. The peak troponin level (n = 14) was 8.5 ng/ml (25th to 75th percentile 5.5 to 37) and the peak creatine kinase-MB (n = 18) was 23 ng/ml (25th to 75th percentile 11 to 55). The electrocardiographic changes at the MI included ST-segment depression (32%), T-wave changes only (18%), and ST-segment elevation (18%). With the available information, we were able to localize only 25% of the MIs (11% anterior, 11% lateral, and 3% inferior). There was no difference at follow-up in either the posterior wall thickness or septal wall thickness between those who did or did not develop a low LVEF ( Table 2 ). However, in those who did versus did not develop a low LVEF, the follow-up LVEDD, LV end-systolic dimension, and change in LVEDD and LV end-systolic dimension from baseline to follow-up were larger (p <0.001 for each). Additionally, the follow-up relative wall thickness was smaller in those who did progress to a low LVEF (p = 0.002) but still remained increased (0.5). In the subjects who developed a low LVEF after long-term follow-up, the median relative wall thickness when stratified by the occurrence of interval MI was 0.49 with interval MI and 0.51 without interval MI. The frequency of heart failure hospitalizations ≥1 year after the index echocardiogram was 13.8% for those without a follow-up echocardiogram, 46% for those with preserved LVEF on the follow-up echocardiogram, and 62% for those with a low LVEF on the follow-up echocardiogram (p <0.001).
| Variable | Progression to Reduced LVEF | p Value | |
|---|---|---|---|
| No (n = 175) | Yes (n = 45) | ||
| Follow-up length (years) | 7.5 ± 4 | 8.6 ± 4 | 0.1 |
| Age at follow-up (years) | 61 ± 12 | 64 ± 15 | 0.3 |
| Systolic blood pressure (mm Hg) | 147 ± 29 | 140 ± 32 | 0.2 |
| Diastolic blood pressure (mm Hg) | 81 ± 15 | 82 ± 21 | 1 |
| Serum creatinine (mg/dl) | 1.1 (0.9–1.4) | 1.5 (1–1.8) | 0.01 |
| Hemodialysis | 13% | 16% | 0.6 |
| Interval myocardial infarction | 9% | 29% | <0.001 |
| Echocardiographic findings | |||
| Posterior wall thickness (cm) | 1.3 (1.1–1.5) | 1.2 (1.1–1.4) | 0.2 |
| Septal wall thickness (cm) | 1.4 (1.2–1.6) | 1.3 (1.2–1.5) | 0.4 |
| Left ventricular end-diastolic dimension (cm) | 4.4 ± 0.7 | 5 ± 0.8 | <0.001 |
| Left ventricular end-systolic dimension (cm) | 2.9 ± 0.6 | 3.9 ± 0.8 | <0.001 |
| Relative wall thickness | 0.6 (0.5–0.8) | 0.5 (0.4–0.6) | 0.002 |
| Change in left ventricular end-diastolic dimension from baseline (cm) | 0.3 ± 0.6 | 0.6 ± 0.8 | 0.004 |
| Change in LV end-systolic dimension from baseline (cm) | 0.02 ± 0.6 | 0.8 ± 0.8 | <0.001 |
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