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Markers of Cardiac Fibrosis Are Similar in African Americans and Caucasians with Heart Failure
S100 Journal of Cardiac Failure Vol. 13 No. 6 Suppl. 2007 with hospital admissions (r 5 0.226, p 5 0.01) and mortality (r 5 0.27, p 5 0.002) even after correcting for age, LVEF, and renal insufficiency (p ! 0.001). These associations were more significant for Hcy than for BNP. Conclusions: These results indicate that Hcy may have a direct effect on LA structure. Plasma Hcy was also found to be an important predictor of clinical outcomes in systolic heart failure.
089 Left Ventricular Remodeling Following Renal Transplantation Lazaros A. Nikolaidis1, Eitan Klein1, Francis Grzywacz1, Aramando L. Samuels2, Alfred A. Bove1; 1Cardiology, Temple University School of Medicine, Philadelphia, PA; 2Nephrology, Temple University School of Medicine, Philadelphia, PA Background: Patients with chronic kidney disease frequently have left ventricular hypertrophy (LVH) related to long-standing hypertension. Diabetes, obesity and metabolic abnormalities also contribute to LVH. In these patients, renal transplantation ameliorates metabolic and electrolyte perturbations, interrupts renin e angiotensin - aldosterone system dysregulation and improves hypertension control. We hypothesized that these factors lead to favorable left ventricular remodeling and LVH regression. However, a salutary net impact could be partially offset by hypertensive effects of calcineurin inhibitors used as immunosuppressant, as well as adverse metabolic impact of corticosteroids used in such clinical setting. Methods: We investigated left ventricular (LV) remodeling in response to renal transplantation by analyzing echocardiograms obtained prior to and following renal transplantation in 30 patients with preserved pre-transplant LV systolic function (LVEF O 40%). Results: Following renal transplantation, there was no significant change in LA (43 6 1 to 44 6 1 mm) or LV dimensions (LVEDD: 49 6 1 to 50 6 1 mm, LVESD: 31 6 1 to 31 6 1 mm), fractional shortening (38 6 1% to 39 6 2%) and LVEF (70 6 2% to 71 6 3%), while LV free wall thickness (12.3 6 0.3 to 13 6 0.1 mm), LV mass (285 6 16 to 335 6 33 g) and LVEDV (114 6 6 to 124 6 8 ml) tended to increase. These findings were independent of the observed attenuation in hypertension (SBP: 161 6 5 to141 6 7, MAP: 112 6 4 to104 6 6 mmHg) but were associated with significant (p ! 0.01) weight gain (76 6 6 to 89 6 7 kg) after transplantation. Adverse remodeling and pro-trophic myocardial response was statistically heterogeneous, being more prevalent (71% vs. 47%) in women compared to men (median change in LVM: þ63 vs. þ1 g, median change in LVEDV þ16 vs. þ4 ml) following renal transplantation. Conclusions: In spite of attenuating systemic hypertension, we observed an overall neutral effect of renal transplantation on structural LV changes with a notable trend toward LVH progression, rather than regression. Adverse LV remodeling was associated with weight gain and was more consistent in women. It is plausible that metabolic mechanisms independent of hypertension that could be further modulated by gender-specific factors and immunosuppressive regimens may account in part for the unanticipated findings.
090 Left Ventricular Structure and Clinical Characteristics of Non-Dilated Cardiomyopathy Alexander Doumas1, Timothy S. Draper, Jr.1, Edgar C. Schick1, William H. Gaasch1; 1 Cardiovascular Medicine, Lahey Clinic Medical Center, Burlington, MA Background: Modern management of patients with chronic heart failure (and those with asymptomatic LV dysfunction) has focused primarily on patients with a low ejection fraction (EF) and LV enlargement/dilatation. However, little attention has been paid to those with non-dilated cardiomyopathy (NDCM). Accordingly, we identified a group of patients with NDCM and sought to examine their LV geometry and clinical characteristics. Methods: Of 3350 transthoracic echocardiograms performed over a 6-month period, 21% had an EF ! 45%. After exclusion of those with LV enlargement (diastolic diameter O 56 mm), those with regional wall motion abnormalities (asynergy) and those with valve disease, 98 patients met criteria for this study. Clinical record review was performed on all 98 patients. Sufficient data (echocardiography) to calculate LV relative wall thickness (Th/R) and mass/volume (M/V) were available in 69 patients. Data are mean 6 SD. Results: The average age was 71 6 14 years; 56% were male. Body mass index was 27 6 5. Comorbidities included: Hypertension 52%. Atrial fibrillation 43%. Bundle branch block 36%. Diabetes mellitus 28%. Chronic renal insufficiency 19%. Hypothyroidism 14%. Only 22% had disabling cardiac symptoms (NYHAFC $ III). The average LV end-diastolic dimension was 49 6 5 mm; EF 5 34 6 8%. Only 9% had LV hypertrophy (LV mass O 105 g/m2), but the average value for M/V (1.4 6 0.3) exceeded the upper limits of normal (range 1.1 - 1.3); M/V O 1.3 was present in 35 of the 69 patients (51%). The average Th/R was 0.43 6 0.10; Th/R O 0.43 was present in 29 patients (42%). Thus concentric remodeling was present in nearly half of these patients. A most striking abnormality was the very low stroke volume of 20 6 5 mL/m2. Conclusion: The pattern of structural remodeling in patients with NDCM appears to be substantially different from that reported in dilated cardiomyopathy. Severe systolic dysfunction can occur in the absence of LV dilatation, suggesting that dilated and non-dilated cardiomyopathies are not separate points along a continuum of a progressive disorder. Optimal long-term treatment of patients with NDCM likely differs from that utilized in dilated hearts.
091 Markers of Cardiac Fibrosis Are Similar in African Americans and Caucasians with Heart Failure Larisa H. Cavallari1, Vicki L. Groo1, Thomas D. Stamos2; 1Pharmacy Practice, University of Illinois at Chicago, Chicago, IL; 2Cardiology, University of Illinois at Chicago, Chicago, IL Background: Spironolactone attenuates cardiac fibrosis and improves survival in heart failure. African Americans are underrepresented in studies with spironolactone, and thus, the benefits of spironolactone in African Americans are unknown. The survival benefits with spironolactone have been positively correlated with baseline markers of cardiac fibrosis, with the greatest survival occurring with procollagen type III amino-terminal peptide (PIIINP) levels O3.85 mg/L. We compared biomarkers of cardiac fibrosis by race in order to determine whether African Americans might benefit from spironolactone. Methods: Serum samples were collected from 60 African Americans and 32 Caucasians with heart failure and left ventricular systolic dysfunction. Patients with renal dysfunction or treatment with an aldosterone antagonist within the previous 12 months were excluded. Procollagen type I amino-terminal peptide (PINP) and PIIINP concentrations were determined by radioimmunoassay. Results: African Americans were younger (47 6 14 vs. 64 6 17 years; p ! 0.01), more likely to be female (53% vs. 16%; p ! 0.01), and had a lower prevalence of ischemic heart disease (18% vs. 63%, p ! 0.01). Heart failure severity, other past medical history, and drug therapy were similar between groups. Procollagen concentrations were also similar between African Americans and Caucasians (table). Fifty-nine percent of African Americans and 69% of Caucasians had PIIINP levels O3.85 mg/L (p 5 NS). Limiting our analysis to males did not alter the results. Conclusion: Despite a lower prevalence of ischemic heart disease, African Americans had procollagen concentrations that were similar to those of Caucasians. Our data suggest that African Americans with heart failure have similar degrees of cardiac fibrosis as Caucasians, and as such, may derive similar benefits from therapies such as spironolactone to limit cardiac remodeling. Procollagens (mg/L)
African Americans (n 5 60)
Caucasians (n 5 32)
65 6 40 5.2 6 2.9
60 6 32 5.6 6 3.0
PINP PIIINP
092 Hypertension in African Americans with Heart Failure: Progression from Hypertrophy to Dilatation; Perhaps Not Ramzan M. Zakir1, Rajiv Patel1, Zulqarnain Abro1, Ather Anis1, Muhamed Saric1, Marc Klapholz1; 1Medicine, UMDNJ-New Jersey Medical School, Newark, NJ Background: It has been thought that concentric hypertrophy (a nondilated, thick walled left ventricle with a normal left ventricular ejection fraction (LVEF) is a common precursor to LV failure (an increased LV volume with a reduced LVEF). Whether or not this occurs in humans is unknown. Methods: We consecutively enrolled African American patients with a history of HTN hospitalized for decompensated volume overloaded heart failure (HF) of a non-ischemic etiology. Patients were divided into normal EF (concentric LV hypertrophy) HF and low EF (LV dilatation) HF. LV mass was calculated: using the ASE formula with Deveruex correction (0.832[(PW þ S þ LVEDD)3 LVEDD] þ 0.6) and indexed to height2.7 (meters) in all patients. Results: Demographic, clinical and echocardiographic results are listed in Table 1. Patients with normal EF HF were significantly older, female, and had a longer duration of HTN. Also, SBP on admission was significantly higher in the normal EF group. LV mass however was significantly greater in the low EF HF group compared to the normal EF HF group. Conclusion: Our study challenges the classic paradigm of hypertensive heart disease stated above. These finding raise the possibility that genetics and gender may play a role in the response of an individual to hypertension.
Table 1. Results
Age (years) Sex (female) Serum Creatinine (mg/dl) Duration of Hypertension (years) Mean SBP at admission (mm Hg) Mean DBP at admission (mm Hg) LVEF (%) LV septal thickness (cm) LV posterior wall thickness (cm) LVEDD (cm) LV mass (g/m2.7)*
Normal EF HF (n 5 60)
Low EF HF (n 5 65)
66 6 14 68% (41/60) 1.3 6 0.9 20 6 6 157 6 33 86 6 23 65.2 6 10 1.30 6 0.3 1.27 6 0.2 4.90 6 0.9 68.11 6 33
62.0 38% 1.2 12 144 86 23.1 1.31 1.28 6.09 87.0
6 12 (25/65) 6 0.1 68 6 26 6 20 67 6 0.3 6 0.3 6 0.9 6 27.8
p-value 0.04 0.001 NS !0.001 0.04 NS !0.001 NS NS ! 0.001 !0.003
*normal LV mass 5 49.2 and 46.7 g/m2.7 in males and females, respectively
089 Left Ventricular Remodeling Following Renal Transplantation Lazaros A. Nikolaidis1, Eitan Klein1, Francis Grzywacz1, Aramando L. Samuels2, Alfred A. Bove1; 1Cardiology, Temple University School of Medicine, Philadelphia, PA; 2Nephrology, Temple University School of Medicine, Philadelphia, PA Background: Patients with chronic kidney disease frequently have left ventricular hypertrophy (LVH) related to long-standing hypertension. Diabetes, obesity and metabolic abnormalities also contribute to LVH. In these patients, renal transplantation ameliorates metabolic and electrolyte perturbations, interrupts renin e angiotensin - aldosterone system dysregulation and improves hypertension control. We hypothesized that these factors lead to favorable left ventricular remodeling and LVH regression. However, a salutary net impact could be partially offset by hypertensive effects of calcineurin inhibitors used as immunosuppressant, as well as adverse metabolic impact of corticosteroids used in such clinical setting. Methods: We investigated left ventricular (LV) remodeling in response to renal transplantation by analyzing echocardiograms obtained prior to and following renal transplantation in 30 patients with preserved pre-transplant LV systolic function (LVEF O 40%). Results: Following renal transplantation, there was no significant change in LA (43 6 1 to 44 6 1 mm) or LV dimensions (LVEDD: 49 6 1 to 50 6 1 mm, LVESD: 31 6 1 to 31 6 1 mm), fractional shortening (38 6 1% to 39 6 2%) and LVEF (70 6 2% to 71 6 3%), while LV free wall thickness (12.3 6 0.3 to 13 6 0.1 mm), LV mass (285 6 16 to 335 6 33 g) and LVEDV (114 6 6 to 124 6 8 ml) tended to increase. These findings were independent of the observed attenuation in hypertension (SBP: 161 6 5 to141 6 7, MAP: 112 6 4 to104 6 6 mmHg) but were associated with significant (p ! 0.01) weight gain (76 6 6 to 89 6 7 kg) after transplantation. Adverse remodeling and pro-trophic myocardial response was statistically heterogeneous, being more prevalent (71% vs. 47%) in women compared to men (median change in LVM: þ63 vs. þ1 g, median change in LVEDV þ16 vs. þ4 ml) following renal transplantation. Conclusions: In spite of attenuating systemic hypertension, we observed an overall neutral effect of renal transplantation on structural LV changes with a notable trend toward LVH progression, rather than regression. Adverse LV remodeling was associated with weight gain and was more consistent in women. It is plausible that metabolic mechanisms independent of hypertension that could be further modulated by gender-specific factors and immunosuppressive regimens may account in part for the unanticipated findings.
090 Left Ventricular Structure and Clinical Characteristics of Non-Dilated Cardiomyopathy Alexander Doumas1, Timothy S. Draper, Jr.1, Edgar C. Schick1, William H. Gaasch1; 1 Cardiovascular Medicine, Lahey Clinic Medical Center, Burlington, MA Background: Modern management of patients with chronic heart failure (and those with asymptomatic LV dysfunction) has focused primarily on patients with a low ejection fraction (EF) and LV enlargement/dilatation. However, little attention has been paid to those with non-dilated cardiomyopathy (NDCM). Accordingly, we identified a group of patients with NDCM and sought to examine their LV geometry and clinical characteristics. Methods: Of 3350 transthoracic echocardiograms performed over a 6-month period, 21% had an EF ! 45%. After exclusion of those with LV enlargement (diastolic diameter O 56 mm), those with regional wall motion abnormalities (asynergy) and those with valve disease, 98 patients met criteria for this study. Clinical record review was performed on all 98 patients. Sufficient data (echocardiography) to calculate LV relative wall thickness (Th/R) and mass/volume (M/V) were available in 69 patients. Data are mean 6 SD. Results: The average age was 71 6 14 years; 56% were male. Body mass index was 27 6 5. Comorbidities included: Hypertension 52%. Atrial fibrillation 43%. Bundle branch block 36%. Diabetes mellitus 28%. Chronic renal insufficiency 19%. Hypothyroidism 14%. Only 22% had disabling cardiac symptoms (NYHAFC $ III). The average LV end-diastolic dimension was 49 6 5 mm; EF 5 34 6 8%. Only 9% had LV hypertrophy (LV mass O 105 g/m2), but the average value for M/V (1.4 6 0.3) exceeded the upper limits of normal (range 1.1 - 1.3); M/V O 1.3 was present in 35 of the 69 patients (51%). The average Th/R was 0.43 6 0.10; Th/R O 0.43 was present in 29 patients (42%). Thus concentric remodeling was present in nearly half of these patients. A most striking abnormality was the very low stroke volume of 20 6 5 mL/m2. Conclusion: The pattern of structural remodeling in patients with NDCM appears to be substantially different from that reported in dilated cardiomyopathy. Severe systolic dysfunction can occur in the absence of LV dilatation, suggesting that dilated and non-dilated cardiomyopathies are not separate points along a continuum of a progressive disorder. Optimal long-term treatment of patients with NDCM likely differs from that utilized in dilated hearts.
091 Markers of Cardiac Fibrosis Are Similar in African Americans and Caucasians with Heart Failure Larisa H. Cavallari1, Vicki L. Groo1, Thomas D. Stamos2; 1Pharmacy Practice, University of Illinois at Chicago, Chicago, IL; 2Cardiology, University of Illinois at Chicago, Chicago, IL Background: Spironolactone attenuates cardiac fibrosis and improves survival in heart failure. African Americans are underrepresented in studies with spironolactone, and thus, the benefits of spironolactone in African Americans are unknown. The survival benefits with spironolactone have been positively correlated with baseline markers of cardiac fibrosis, with the greatest survival occurring with procollagen type III amino-terminal peptide (PIIINP) levels O3.85 mg/L. We compared biomarkers of cardiac fibrosis by race in order to determine whether African Americans might benefit from spironolactone. Methods: Serum samples were collected from 60 African Americans and 32 Caucasians with heart failure and left ventricular systolic dysfunction. Patients with renal dysfunction or treatment with an aldosterone antagonist within the previous 12 months were excluded. Procollagen type I amino-terminal peptide (PINP) and PIIINP concentrations were determined by radioimmunoassay. Results: African Americans were younger (47 6 14 vs. 64 6 17 years; p ! 0.01), more likely to be female (53% vs. 16%; p ! 0.01), and had a lower prevalence of ischemic heart disease (18% vs. 63%, p ! 0.01). Heart failure severity, other past medical history, and drug therapy were similar between groups. Procollagen concentrations were also similar between African Americans and Caucasians (table). Fifty-nine percent of African Americans and 69% of Caucasians had PIIINP levels O3.85 mg/L (p 5 NS). Limiting our analysis to males did not alter the results. Conclusion: Despite a lower prevalence of ischemic heart disease, African Americans had procollagen concentrations that were similar to those of Caucasians. Our data suggest that African Americans with heart failure have similar degrees of cardiac fibrosis as Caucasians, and as such, may derive similar benefits from therapies such as spironolactone to limit cardiac remodeling. Procollagens (mg/L)
African Americans (n 5 60)
Caucasians (n 5 32)
65 6 40 5.2 6 2.9
60 6 32 5.6 6 3.0
PINP PIIINP
092 Hypertension in African Americans with Heart Failure: Progression from Hypertrophy to Dilatation; Perhaps Not Ramzan M. Zakir1, Rajiv Patel1, Zulqarnain Abro1, Ather Anis1, Muhamed Saric1, Marc Klapholz1; 1Medicine, UMDNJ-New Jersey Medical School, Newark, NJ Background: It has been thought that concentric hypertrophy (a nondilated, thick walled left ventricle with a normal left ventricular ejection fraction (LVEF) is a common precursor to LV failure (an increased LV volume with a reduced LVEF). Whether or not this occurs in humans is unknown. Methods: We consecutively enrolled African American patients with a history of HTN hospitalized for decompensated volume overloaded heart failure (HF) of a non-ischemic etiology. Patients were divided into normal EF (concentric LV hypertrophy) HF and low EF (LV dilatation) HF. LV mass was calculated: using the ASE formula with Deveruex correction (0.832[(PW þ S þ LVEDD)3 LVEDD] þ 0.6) and indexed to height2.7 (meters) in all patients. Results: Demographic, clinical and echocardiographic results are listed in Table 1. Patients with normal EF HF were significantly older, female, and had a longer duration of HTN. Also, SBP on admission was significantly higher in the normal EF group. LV mass however was significantly greater in the low EF HF group compared to the normal EF HF group. Conclusion: Our study challenges the classic paradigm of hypertensive heart disease stated above. These finding raise the possibility that genetics and gender may play a role in the response of an individual to hypertension.
Table 1. Results
Age (years) Sex (female) Serum Creatinine (mg/dl) Duration of Hypertension (years) Mean SBP at admission (mm Hg) Mean DBP at admission (mm Hg) LVEF (%) LV septal thickness (cm) LV posterior wall thickness (cm) LVEDD (cm) LV mass (g/m2.7)*
Normal EF HF (n 5 60)
Low EF HF (n 5 65)
66 6 14 68% (41/60) 1.3 6 0.9 20 6 6 157 6 33 86 6 23 65.2 6 10 1.30 6 0.3 1.27 6 0.2 4.90 6 0.9 68.11 6 33
62.0 38% 1.2 12 144 86 23.1 1.31 1.28 6.09 87.0
6 12 (25/65) 6 0.1 68 6 26 6 20 67 6 0.3 6 0.3 6 0.9 6 27.8
p-value 0.04 0.001 NS !0.001 0.04 NS !0.001 NS NS ! 0.001 !0.003
*normal LV mass 5 49.2 and 46.7 g/m2.7 in males and females, respectively