Concentric remodeling (CR) is defined as increased left ventricular (LV) wall thickness with normal total LV mass. When encountered in populations with hypertension or patients undergoing aortic valve replacement, some studies have shown that CR predicts cardiovascular (CV) events and stroke. To expand our understanding of the prognostic implications of this common echocardiographic finding, we examined the association of CR and adverse CV events in ambulatory patients with coronary artery disease (CAD). We tested the hypothesis that finding CR on echocardiogram in ambulatory CAD independently predicts heart failure hospitalizations and CV death. Transthoracic echocardiograms were recorded in 973 participants from the Heart and Soul Study. Participants were divided into 4 groups: normal, CR, concentric LV hypertrophy, and eccentric LV hypertrophy. CV events were determined by 2 independent adjudicators and these were analyzed by Cox proportional hazards models. After mean 4.9 ± 1.5 years of follow-up, adverse outcomes occurred more frequently in those with concentric and eccentric LV hypertrophy but not in those with CR. After multivariate adjustment, concentric and eccentric LV hypertrophies were associated with increased risk of death and heart failure hospitalization, whereas CR was not. In conclusion, our hypothesis was not supported because CR was not associated with adverse CV events in our cohort of patients with stable CAD.
The left ventricle remodels in response to long-term increased volume or pressure, most commonly resulting in hypertrophy. This transformation allows the left ventricle to decrease systolic wall stress and preserve contractile function. The American Society of Echocardiography categorizes left ventricular (LV) remodeling as concentric remodeling (CR), concentric LV hypertrophy, and eccentric LV hypertrophy and defines CR as increased relative wall thickness with normal LV mass. It is known that CR predicts cardiovascular (CV) events and stroke and is associated with adverse CV outcomes in patients with hypertension and in those undergoing aortic valve replacement ; however, these relations have not been defined in patients with established coronary artery disease (CAD). Therefore, we sought to determine the prognostic value of CR in a contemporary population of ambulatory patients with stable CAD and hypothesized that CR independently predicts heart failure hospitalizations and CV death.
Methods
Patients were enrolled in the Heart and Soul Study, a prospective cohort study investigating the influence of psychosocial factors on CV events. Methods have been described previously. Administrative databases were used to identify outpatients with documented CAD at 2 Department of Veterans Affairs medical center databases (San Francisco and Palo Alto, California), a university-based medical center (University of California Medical Center–San Francisco), and 9 public health clinics in the Community Health Network of San Francisco, California. Criteria for enrollment included (1) history of myocardial infarction that healed, (2) angiographic evidence of ≥50% stenosis in ≥1 coronary artery (with or without previous myocardial infarction), (3) previous evidence of exercise-induced ischemia using treadmill electrocardiography or stress nuclear perfusion imaging, or (4) previous coronary revascularization. Patients were excluded if they deemed themselves unable to walk 1 block, had an acute coronary syndrome in the previous 6 months, or were planning to move from the local area within 3 years.
We performed standard echocardiography using a commercially available ultrasound system with harmonic imaging (Acuson Sequoia, Siemens Corporation, Mountain View, California). LV volumes and ejection fraction were measured quantitatively using the 2-dimensional (2D) echocardiographic biplane method of disks. LV mass was measured using the 2D echocardiographic truncated ellipse method. LV posterior wall thickness was measured at end-diastole from 2D recordings according to recommended methods.
Normal LV end-diastolic volume index was defined as ≤75 ml/m 2 . Normal LV mass index was defined as ≤88 g/m 2 for women and ≤102 g/m 2 for men. Normal LV posterior wall thickness was defined as <1.1 cm. Participants were classified into 4 groups of LV geometry: normal, CR, concentric LV hypertrophy, and eccentric LV hypertrophy. CR was defined as normal LV mass index, normal LV end-diastolic volume index, and increased LV posterior wall thickness; concentric LV hypertrophy was defined as increased LV mass index and normal LV end-diastolic volume index; and eccentric LV hypertrophy was defined as increased LV mass index and increased LV end-diastolic volume index. We excluded participants with normal LV mass index and increased LV end-diastolic volume index and those without complete echocardiographic measurements caused by technical difficulty. A single cardiologist (N.B.S.) blinded to clinical and laboratory information evaluated all echocardiograms.
Each participant completed a detailed questionnaire that included age, gender, race, medical history, level of physical activity, current smoking, and level of alcohol consumption. Study personnel recorded all current medications and measured height, weight, and blood pressure. Medication categories were categorized using Epocrates Rx. (San Mateo, California).
Prespecified end points included incident heart failure hospitalization, all-cause mortality, and death from heart disease during follow-up. We conducted annual telephone follow-up interviews with participants (or their proxies) to ask about death or hospitalization for “heart trouble.” For any reported event, medical records, electrocardiograms, death certificates, and coroner’s reports were retrieved and reviewed by 2 independent and blinded adjudicators. If the adjudicators agreed on the outcome classification, their classification was binding. In the event of disagreement, the adjudicators conferred, reconsidered their classification, and requested consultation from a third blinded adjudicator.
All-cause mortality was determined by review of death certificates. Myocardial infarction was defined using standard diagnostic criteria. Death was considered caused by CAD if (1) the participant died during the same hospitalization in which acute myocardial infarction was the primary diagnosis or (2) the participant had sudden CAD death defined as an unexpected, otherwise unexplained fatality within 1 hour of onset of terminal symptoms.
Hospitalization for heart failure was defined as hospital admission for a clinical syndrome involving ≥2 of the following: paroxysmal nocturnal dyspnea, orthopnea, increased jugular venous pressure, pulmonary rales, third heart sound, cardiomegaly on chest x-ray, or pulmonary edema on chest x-ray. These clinical signs and symptoms must have represented a clear change from the normal clinical state of the patient and must have been accompanied by failing cardiac output as determined by peripheral hypoperfusion (hypotension in the absence of other causes such as sepsis or dehydration) or peripheral or pulmonary edema. Supportive documentations of decreased cardiac index, increasing pulmonary capillary wedge pressure, decreasing oxygen saturation, and end-organ hypoperfusion, if available, were included in adjudication. The study protocol was approved by the institutional review board at each participating site, and all participants provided written informed consent.
The goal of this study was to examine the association of CR with CV outcomes. Differences in participant characteristics by pattern of ventricular remodeling (normal, CR, concentric LV hypertrophy, and eccentric LV hypertrophy) were determined using analysis of variance of continuous variables and chi-square tests for dichotomous variables. Analyses were performed using SAS 9 (SAS Institute, Cary, North Carolina). We used Cox proportional hazard models to evaluate the independent association of LV geometry with CV events and included analysis of unadjusted data and multivariable adjusted outcomes. For these analyses, we report hazard ratios with 95% confidence intervals. A Kaplan–Meier plot aggregated CV events by date during follow-up for each group.
Results
From September 2000 through December 2002, 1,024 participants were enrolled in the Heart and Soul Study. From this cohort, 973 participants remained in the analytic sample after exclusions, of which 304 (31%) were normal, 262 (27%) had CR, 322 (33%) had concentric LV hypertrophy, and 85 (9%) had eccentric LV hypertrophy.
Table 1 lists baseline characteristics of participants according to ventricular remodeling type. By definition, LV end-diastolic volume index was highest in participants with eccentric LV hypertrophy. In addition, LV wall thickness and LV mass index were highest in participants with LV hypertrophy. Table 2 lists baseline characteristics of those without remodeling (“normal”) and those with CR only. By definition, LV wall thickness was greater in participants with CR. Furthermore, although patients with CR had LV mass indexes within normal limits, these were significantly higher than in normal participants.
| Variable | Normal (n = 304) | CR (n = 262) | Concentric LV Hypertrophy (n = 322) | Eccentric LV Hypertrophy (n = 85) | p Value |
|---|---|---|---|---|---|
| Age (years) | 66 ± 11 | 66 ± 10 | 67 ± 11 | 68 ± 10 | 0.19 |
| Men | 228 (75%) | 227 (87%) | 258 (80%) | 77 (91%) | 0.0005 |
| Race | |||||
| White | 178 (59%) | 168 (64%) | 181 (56%) | 54 (64%) | 0.22 |
| Black | 40 (13%) | 45 (17%) | 62 (19%) | 16 (19%) | 0.21 |
| Asian | 46 (13%) | 25 (10%) | 33 (10%) | 9 (11%) | 0.14 |
| Other | 39 (13%) | 24 (9%) | 46 (14%) | 6 (7%) | 0.12 |
| Medical history | |||||
| Hypertension | 183 (60%) | 189 (72%) | 253 (79%) | 61 (73%) | <0.0001 |
| Diabetes mellitus | 61 (20%) | 67 (26%) | 105 (33%) | 91 (23%) | 0.004 |
| Myocardial infarction | 155 (51%) | 119 (46%) | 175 (55%) | 69 (82%) | <0.0001 |
| Stroke | 39 (13%) | 37 (14%) | 48 (15%) | 15 (18%) | 0.68 |
| Heart failure | 35 (12%) | 28 (11%) | 66 (21%) | 39 (46%) | <0.0001 |
| Revascularization | 180 (59%) | 143 (55%) | 189 (59%) | 54 (64%) | 0.47 |
| Medications | |||||
| Diuretic | 67 (22%) | 61 (23%) | 121 (38%) | 34 (40%) | <0.0001 |
| β Blocker | 167 (55%) | 141 (54%) | 197 (61%) | 59 (69%) | 0.03 |
| Angiotensin-converting enzyme inhibitor or angiotensin receptor blocker | 121 (40%) | 124 (47%) | 190 (59%) | 62 (73%) | <0.0001 |
| Systolic blood pressure (mm Hg) | 128.9 ± 18.8 | 132.2 ± 18.4 | 139.2 ± 23.5 | 127.8 ± 20.5 | <0.0001 |
| Body mass index (kg/m 2 ) | 26.9 ± 4.4 | 29.6 ± 5.2 | 29.2 ± 5.6 | 26.3 ± 4.3 | <0.0001 |
| Left ventricular end-diastolic volume index (ml/m 2 ) | 46.1 ± 10.9 | 44.8 ± 10.3 | 50.8 ± 12.1 | 93.9 ± 19.5 | <0.0001 |
| Left ventricular mass index (g/m 2 ) | 80.0 ± 11.9 | 84.7 ± 10.2 | 120.4 ± 41.5 | 139.5 ± 27.9 | <0.0001 |
| Left ventricular ejection fraction | 64.5 ± 6.9 | 64.8 ± 5.9 | 61.0 ± 9.2 | 45.8 ± 12.1 | <0.0001 |
| Septal thickness (cm) | 1.1 ± 0.1 | 1.3 ± 0.2 | 1.4 ± 0.3 | 1.2 ± 0.3 | <0.0001 |
| Posterior wall thickness (cm) | 1.0 ± 0.1 | 1.2 ± 0.4 | 1.2 ± 0.2 | 1.2 ± 0.2 | <0.0001 |
| Variable | Normal (n = 304) | CR (n = 262) | p Value |
|---|---|---|---|
| Age (years) | 66 ± 11 | 66 ± 10 | 0.47 |
| Men | 228 (75%) | 227 (87%) | 0.0005 |
| Race | 0.06 | ||
| White | 178 (59%) | 168 (64%) | — |
| Black | 40 (13%) | 45 (17%) | — |
| Asian | 46 (13%) | 25 (10%) | — |
| Other | 39 (13%) | 24 (9%) | — |
| Medical history | |||
| Hypertension | 183 (60%) | 189 (72%) | 0.002 |
| Diabetes mellitus | 61 (20%) | 67 (26%) | 0.11 |
| Myocardial infarction | 155 (51%) | 119 (46%) | 0.19 |
| Stroke | 39 (13%) | 37 (14%) | 0.64 |
| Revascularization | 35 (12%) | 28 (11%) | 0.76 |
| Heart failure | 180 (59%) | 143 (55%) | 0.31 |
| Medications | |||
| Diuretic | 67 (22%) | 61 (23%) | 0.72 |
| β Blocker | 167 (55%) | 141 (54%) | 0.79 |
| Angiotensin-converting enzyme inhibitor or angiotensin receptor blocker | 121 (40%) | 124 (47%) | 0.07 |
| Systolic blood pressure (mm Hg) | 128.9 ± 18.8 | 132.2 ± 18.4 | 0.04 |
| Body mass index (kg/m 2 ) | 26.9 ± 4.4 | 29.6 ± 5.2 | <0.0001 |
| Left ventricular end-diastolic volume index (ml/m 2 ) | 46.1 ± 10.9 | 44.8 ± 10.3 | 0.14 |
| Left ventricular mass index (g/m 2 ) | 80.0 ± 11.9 | 84.7 ± 10.2 | <0.0001 |
| Left ventricular ejection fraction | 64.5 ± 6.9 | 64.8 ± 5.9 | 0.53 |
| Septal thickness (cm) | 1.1 ± 0.1 | 1.3 ± 0.2 | <0.0001 |
| Posterior wall thickness (cm) | 1.0 ± 0.1 | 1.2 ± 0.4 | <0.0001 |
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