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Coronary microvascular dysfunction in patients with symptomatic hypertrophic cardiomyopathy
The 8th Annual Scientific Meeting
•
HFSA
S33
053
055
Health Status among Elderly Hospitalized Patients with Heart Failure and Anemia: A Significant Impact of Anemia on Symptoms in Patients with Heart Failure and Normal Ejection Fraction Asia Mubashir, Rose Cohen, Raja Junaid Wajahat, Mathew S. Maurer; Medicine, Columbia University, NY, NY
Early Detection of Myocardial Involvement by Strain Doppler Echocardiography in Patients with Acromegaly Antonio Vitarelli, Ysabel Conde, Ester Cimino, Simona D’Orazio, Ilaria D’Angeli, Simona Stellato, Viviana Padella, Fabrizio Diacono, Patrizia Gargiulo, Guido Tamburrano; Cardio-thoracic and Medical Depts., La Sapienza University, Rome, Italy
Anemia is common in patients with heart failure. Among patients with heart failure low ejection fraction (HFLEF), the significant impact of anemia on clinical status has been characterized. We sought to determine the impact of anemia on clinical outcomes and health status in elderly hospitalized patients with heart failure normal ejection fraction (HFNEF). Methods: 227 consecutive hospitalized HF patients were studied. Anemia was defined by WHO criteria (Hgb ⬍12 in women and ⬍13 in men). A subset of 81 patients underwent assessment of health status using the Kansas City Cardiomyopathy Questionnaire (KCCQ), a 23-item questionnaire that quantifies physical limitations, symptoms, self-efficacy, social interference and quality of life. Scores on various domains were compared among subjects with anemia and no anemia stratified by ejection fraction using a student’s t test for unpaired comparisons. Results: The subjects were 77 ⫾ 14 years of age, 59% were women, 44% had a normal ejection fraction and 64% were anemic. The age of the HF subjects with anemia and without anemia did not differ (78 ⫾ 14 vs 76 ⫾ 14 years), nor did the rate of previous hospitalizations, irrespective of ejection fraction. However, subjects with anemia had longer lengths of stay (median 8 vs 5 days, p ⬍ 0.05) than those without anemia. Clinical outcomes and score on the KCCQ are shown below. Anemic patients with HFNEF had on average lower scores on all domains than nonanemic subjects and significantly lower symptoms scores compared to no anemia and HFNEF. Conclusions: The prevalence of anemia among patients with HFNEF is comparable to subjects with HFLEF. Length of stay is longer among anemic subjects hospitalized with heart failure. Moreover, symptoms scores are significantly worse among anemic subjects hospitalized with HFNEF. These findings warrant future studies to determine the impact of treating anemia in HFNEF.
Background: A considerable literature suggests that there is a specific cardiomyopathy in acromegaly, resulting in structural and functional abnormalities that may be partially reversed by effective reduction in growth hormone / insulin-like growth factor I (GH/IGF-I) levels. Recent reports suggest that structural changes can occur after short-term exposure to GH. The aim of our study was the early detection of subclinical cardiac involvement in patients with acromegalia using tissue Doppler (TDI) and strain Doppler (SR) imaging. Methods: Thirty-nine patients with acromegalia underwent physical examination, electrocardiogram, and standard transthoracic echocardiogram in order to exclude those with cardiac involvement. The remaining twenty-seven patients without clinical and echocardiographic cardiac involvement (group 1, age 51 ⫾ 13 years, 16 females) were compared to 24 sex and age-matched controls (group 2, age 49 ⫾ 12 years, 11 females). Left and right ventricular ejection fraction (LVEF, RVEF), fractional shortening (LVFS, RVFS), and mitral and tricuspid flow filling parameters (MV and TV E/A ratio, MV and TV DT) were determined. Offline analysis of the myocardial velocity data sets was performed using dedicated software (Aplio, Toshiba Corp.). Velocity and strain traces from left and right ventricular free wall at 3 levels (basal, mid cavity, and apical) were processed from the same wall site in the apical 4-chamber view. Systolic (Sw) and diastolic (Ew, Aw) wall velocities as well as peak systolic strain (ε) and systolic and diastolic (isovolumic, early and late diastolic) SR values (SR-S, SR-IVR, SR-E, SR-A) were determined. Results: Dimensions of left and right atrial and ventricular chambers were similar between the two groups. No significant differences were determined between the two groups for the following parameters: LVEF, RVEF, LVFS, RVFS, MV and TV E/A ratio, MV and TV DT. A significant difference was found between the two groups for MV and TV Ew/Aw ratio at basal level (p ⬍ 0.001 and p ⬍ 0.05, respectively). Left and right ventricular peak systolic ε and systolic and early diastolic SR values were significantly reduced compared to controls at basal (p ⬍ 0.001) and mid-cavity level (p ⬍ 0.005) but not at apical level. Conclusion: In patients with acromegaly TDI/ SR parameters (mainly from basal ventricular segments) can show a possible early cardiac involvement not detected by conventional echocardiography.
HFLEF Domain Number of Subjects Physical limitation Symptoms Quality of life Social limitation Self-efficacy KCCQ functional status KCCQ clinical summary
HFNEF
No Anemia
Anemia
No Anemia
Anemia
15 26 ⫾ 7 43 ⫾ 6 38 ⫾ 6 30 ⫾ 9 68 ⫾ 8 35 ⫾ 4 36 ⫾ 3
24 31 ⫾ 6 40 ⫾ 4 41 ⫾ 1 47 ⫾ 7 82 ⫾ 4 39 ⫾ 4 44 ⫾ 4
20 43 ⫾ 7 47 ⫾ 5 45 ⫾ 7 38 ⫾ 7 70 ⫾ 6 45 ⫾ 5 46 ⫾ 5
22 30 ⫾ 6 34 ⫾ 4* 29 ⫾ 5 30 ⫾ 7 68 ⫾ 7 35 ⫾ 4 34 ⫾ 4
*p ⬍ 0.05 anemia vs. no anemia, Values are Mean ⫹ SE
054
056
Ventricular Structure and Function after Prolonged Pressure Overload in the Mouse Jeetendra B. Patel,1 Gerald E. Harders,1 Margaret M. Redfield1; 1Cardiorenal Research Laboratory, Mayo Clinic College of Medicine, Rochester, MN
Coronary Microvascular Dysfunction in Patients with Symptomatic Hypertrophic Cardiomyopathy Eric H. Yang,1 Stuart T. Higano,1 Rick A. Nishimura,1 Amir Lerman1; 1Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, Rochester, MN
Heart failure (HF) with normal ejection fraction (EF), “diastolic” HF (DHF), usually occurs in patients with longstanding hypertension. While impaired relaxation (Tau) and increased diastolic stiffness (β) are reported to mediate elevated filling pressures in DHF, others have reported that diastolic function is not impaired in DHF but that LV systolic (Ees) and arterial stiffness are increased. The myocardial histology associated with functional alterations in DHF is not well defined. Objective: As the life span of mice (≈2 years) allows study of the natural history of pressure overload (POL) over a relatively time short period, we characterized LV structure and function in mice with prolonged POL produced by supra-renal aortic banding. Methods: 12 week old FVB mice underwent suprarenal aortic banding (BAND; n ⫽ 15) or sham surgery (SHAM; n ⫽ 25). Of these, 13 BAND and 11 SHAM were studied with a 1.4 Fr.conductance catheter (avertin anesthesia; steady state and variable preload data) at 20 weeks after banding, a banded duration equivalent to ≈22% average remaining life-span. Results: (see table) LV volume and EF were similar in BAND and SHAM. The LV/body weight ratio was 1.35 × SHAM (p ⬍ 0.0001) and the % area occupied by perivascular (3.4 × SHAM) and interstitial (3.2 × SHAM) fibrosis was markedly increased (p ⬍ 0.0001 for both). Lung/body weight tended to be higher (1.1 × SHAM, p ⫽ 0.07) in BAND. End systolic pressure and Ees were higher, while preload recruitable stroke work was similar (1.2 × SHAM, p ⫽ 0.22) in BAND vs SHAM. End diastolic pressures (3 × SHAM) and Tau (1.5 × SHAM) were increased but diastolic stiffness (β) was similar to SHAM. Conclusions: Prolonged POL in the mouse leads to hypertrophy, marked fibrosis and signs of HF (increased diastolic pressure and lung weight) without LV dilation or reduced EF. Relaxation was impaired and the end diastolic pressure volume relationship was shifted upward, without a change in steepness of its slope. Systolic stiffness was increased while other measures of contractile performance were not, suggesting that hypertrophy and fibrosis rather than enhanced contractility altered Ees. These data support a role for both diastolic dysfunction and systolic stiffness in the pathogenesis of DHF related to POL.
Background: Patients with hypertrophic cardiomyopathy (HCM) have been shown to have reduced myocardial perfusion in the presence of normal epicardial arteries. The mechanism of abnormal microvascular function is not well understood. Hypothesis: A possible mechanism for the reduction in CFR may be that the microcirculation is already near maximal dilation in the basal state and is therefore limited in the ability to further dilate and compensate for the increase in myocardial demand. Methods: Eight patients with symptomatic HCM and eight age- and sex-matched controls were studied. All patients underwent coronary angiography and coronary hemodynamic assessment with an intracoronary Doppler wire to determine total coronary blood flow, coronary resistance, and coronary flow reserve (CFR). Phasic blood flow parameters were also obtained. Results: Compared with controls (n ⫽ 8), patients with HCM (n ⫽ 8) had higher coronary blood flow (52 ⫾ 19 versus 33 ⫾ 11 mL/min, P ⫽ 0.03), lower coronary resistance (2.12 ⫾ 0.91 versus 3.13 ⫾ 0.93 mm Hg/mL/min, P ⫽ 0.05), and lower CFR (2.1 ⫾ 0.7 versus 3.4 ⫾ 1.0 mm, P ⫽ 0.02). There was a direct correlation between CFR and coronary resistance (r ⫽ .5, P ⫽ .05). HCM patients also had abnormal phasic coronary flow characteristics with lower systolic velocities or reversal of flow during systole, and a more rapid deceleration of diastolic blood flow (40.7 ⫾ 13.2 versus 27.5 ⫾ 8.5 cm/sec2, P ⫽ .03). Conclusion: The reduction of CFR in HCM patients may be secondary to near maximal vasodilatation of the microcirculation in the basal state rather than narrowing of intramyocardial small arteries. Symptomatic HCM patients also have abnormal phasic coronary blood flow with a greater dependence on diastolic flow and a more rapid deceleration of diastolic blood flow.
End Systolic P (mmHg) LV End Diastolic P (mmHg) End Diastolic Volume (ul) Ejection Fraction (%) End systolic Stiffness (Ees, mmHg/ul) Diastolic stiffness β (mmHg/ul) Tau (ms) (logistic) mean ⫾ sem; *p ⬍ 0.05 vs SHAM
SHAM
BAND
59 ⫾ 3 ⫺1.5 ⫾ 0.9 16.4 ⫾ 1.1 66 ⫾ 3 8.5 ⫾ 1.3 0.111 ⫾ 0.021 5.1 ⫾ 0.2
69 ⫾ 3* 3.3 ⫾ 0.9* 15.5 ⫾ 1.1 63 ⫾ 3 18.4 ⫾ 3.5* 0.117 ⫾ 0.123 7.8 ⫾ 0.4*
•
HFSA
S33
053
055
Health Status among Elderly Hospitalized Patients with Heart Failure and Anemia: A Significant Impact of Anemia on Symptoms in Patients with Heart Failure and Normal Ejection Fraction Asia Mubashir, Rose Cohen, Raja Junaid Wajahat, Mathew S. Maurer; Medicine, Columbia University, NY, NY
Early Detection of Myocardial Involvement by Strain Doppler Echocardiography in Patients with Acromegaly Antonio Vitarelli, Ysabel Conde, Ester Cimino, Simona D’Orazio, Ilaria D’Angeli, Simona Stellato, Viviana Padella, Fabrizio Diacono, Patrizia Gargiulo, Guido Tamburrano; Cardio-thoracic and Medical Depts., La Sapienza University, Rome, Italy
Anemia is common in patients with heart failure. Among patients with heart failure low ejection fraction (HFLEF), the significant impact of anemia on clinical status has been characterized. We sought to determine the impact of anemia on clinical outcomes and health status in elderly hospitalized patients with heart failure normal ejection fraction (HFNEF). Methods: 227 consecutive hospitalized HF patients were studied. Anemia was defined by WHO criteria (Hgb ⬍12 in women and ⬍13 in men). A subset of 81 patients underwent assessment of health status using the Kansas City Cardiomyopathy Questionnaire (KCCQ), a 23-item questionnaire that quantifies physical limitations, symptoms, self-efficacy, social interference and quality of life. Scores on various domains were compared among subjects with anemia and no anemia stratified by ejection fraction using a student’s t test for unpaired comparisons. Results: The subjects were 77 ⫾ 14 years of age, 59% were women, 44% had a normal ejection fraction and 64% were anemic. The age of the HF subjects with anemia and without anemia did not differ (78 ⫾ 14 vs 76 ⫾ 14 years), nor did the rate of previous hospitalizations, irrespective of ejection fraction. However, subjects with anemia had longer lengths of stay (median 8 vs 5 days, p ⬍ 0.05) than those without anemia. Clinical outcomes and score on the KCCQ are shown below. Anemic patients with HFNEF had on average lower scores on all domains than nonanemic subjects and significantly lower symptoms scores compared to no anemia and HFNEF. Conclusions: The prevalence of anemia among patients with HFNEF is comparable to subjects with HFLEF. Length of stay is longer among anemic subjects hospitalized with heart failure. Moreover, symptoms scores are significantly worse among anemic subjects hospitalized with HFNEF. These findings warrant future studies to determine the impact of treating anemia in HFNEF.
Background: A considerable literature suggests that there is a specific cardiomyopathy in acromegaly, resulting in structural and functional abnormalities that may be partially reversed by effective reduction in growth hormone / insulin-like growth factor I (GH/IGF-I) levels. Recent reports suggest that structural changes can occur after short-term exposure to GH. The aim of our study was the early detection of subclinical cardiac involvement in patients with acromegalia using tissue Doppler (TDI) and strain Doppler (SR) imaging. Methods: Thirty-nine patients with acromegalia underwent physical examination, electrocardiogram, and standard transthoracic echocardiogram in order to exclude those with cardiac involvement. The remaining twenty-seven patients without clinical and echocardiographic cardiac involvement (group 1, age 51 ⫾ 13 years, 16 females) were compared to 24 sex and age-matched controls (group 2, age 49 ⫾ 12 years, 11 females). Left and right ventricular ejection fraction (LVEF, RVEF), fractional shortening (LVFS, RVFS), and mitral and tricuspid flow filling parameters (MV and TV E/A ratio, MV and TV DT) were determined. Offline analysis of the myocardial velocity data sets was performed using dedicated software (Aplio, Toshiba Corp.). Velocity and strain traces from left and right ventricular free wall at 3 levels (basal, mid cavity, and apical) were processed from the same wall site in the apical 4-chamber view. Systolic (Sw) and diastolic (Ew, Aw) wall velocities as well as peak systolic strain (ε) and systolic and diastolic (isovolumic, early and late diastolic) SR values (SR-S, SR-IVR, SR-E, SR-A) were determined. Results: Dimensions of left and right atrial and ventricular chambers were similar between the two groups. No significant differences were determined between the two groups for the following parameters: LVEF, RVEF, LVFS, RVFS, MV and TV E/A ratio, MV and TV DT. A significant difference was found between the two groups for MV and TV Ew/Aw ratio at basal level (p ⬍ 0.001 and p ⬍ 0.05, respectively). Left and right ventricular peak systolic ε and systolic and early diastolic SR values were significantly reduced compared to controls at basal (p ⬍ 0.001) and mid-cavity level (p ⬍ 0.005) but not at apical level. Conclusion: In patients with acromegaly TDI/ SR parameters (mainly from basal ventricular segments) can show a possible early cardiac involvement not detected by conventional echocardiography.
HFLEF Domain Number of Subjects Physical limitation Symptoms Quality of life Social limitation Self-efficacy KCCQ functional status KCCQ clinical summary
HFNEF
No Anemia
Anemia
No Anemia
Anemia
15 26 ⫾ 7 43 ⫾ 6 38 ⫾ 6 30 ⫾ 9 68 ⫾ 8 35 ⫾ 4 36 ⫾ 3
24 31 ⫾ 6 40 ⫾ 4 41 ⫾ 1 47 ⫾ 7 82 ⫾ 4 39 ⫾ 4 44 ⫾ 4
20 43 ⫾ 7 47 ⫾ 5 45 ⫾ 7 38 ⫾ 7 70 ⫾ 6 45 ⫾ 5 46 ⫾ 5
22 30 ⫾ 6 34 ⫾ 4* 29 ⫾ 5 30 ⫾ 7 68 ⫾ 7 35 ⫾ 4 34 ⫾ 4
*p ⬍ 0.05 anemia vs. no anemia, Values are Mean ⫹ SE
054
056
Ventricular Structure and Function after Prolonged Pressure Overload in the Mouse Jeetendra B. Patel,1 Gerald E. Harders,1 Margaret M. Redfield1; 1Cardiorenal Research Laboratory, Mayo Clinic College of Medicine, Rochester, MN
Coronary Microvascular Dysfunction in Patients with Symptomatic Hypertrophic Cardiomyopathy Eric H. Yang,1 Stuart T. Higano,1 Rick A. Nishimura,1 Amir Lerman1; 1Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, Rochester, MN
Heart failure (HF) with normal ejection fraction (EF), “diastolic” HF (DHF), usually occurs in patients with longstanding hypertension. While impaired relaxation (Tau) and increased diastolic stiffness (β) are reported to mediate elevated filling pressures in DHF, others have reported that diastolic function is not impaired in DHF but that LV systolic (Ees) and arterial stiffness are increased. The myocardial histology associated with functional alterations in DHF is not well defined. Objective: As the life span of mice (≈2 years) allows study of the natural history of pressure overload (POL) over a relatively time short period, we characterized LV structure and function in mice with prolonged POL produced by supra-renal aortic banding. Methods: 12 week old FVB mice underwent suprarenal aortic banding (BAND; n ⫽ 15) or sham surgery (SHAM; n ⫽ 25). Of these, 13 BAND and 11 SHAM were studied with a 1.4 Fr.conductance catheter (avertin anesthesia; steady state and variable preload data) at 20 weeks after banding, a banded duration equivalent to ≈22% average remaining life-span. Results: (see table) LV volume and EF were similar in BAND and SHAM. The LV/body weight ratio was 1.35 × SHAM (p ⬍ 0.0001) and the % area occupied by perivascular (3.4 × SHAM) and interstitial (3.2 × SHAM) fibrosis was markedly increased (p ⬍ 0.0001 for both). Lung/body weight tended to be higher (1.1 × SHAM, p ⫽ 0.07) in BAND. End systolic pressure and Ees were higher, while preload recruitable stroke work was similar (1.2 × SHAM, p ⫽ 0.22) in BAND vs SHAM. End diastolic pressures (3 × SHAM) and Tau (1.5 × SHAM) were increased but diastolic stiffness (β) was similar to SHAM. Conclusions: Prolonged POL in the mouse leads to hypertrophy, marked fibrosis and signs of HF (increased diastolic pressure and lung weight) without LV dilation or reduced EF. Relaxation was impaired and the end diastolic pressure volume relationship was shifted upward, without a change in steepness of its slope. Systolic stiffness was increased while other measures of contractile performance were not, suggesting that hypertrophy and fibrosis rather than enhanced contractility altered Ees. These data support a role for both diastolic dysfunction and systolic stiffness in the pathogenesis of DHF related to POL.
Background: Patients with hypertrophic cardiomyopathy (HCM) have been shown to have reduced myocardial perfusion in the presence of normal epicardial arteries. The mechanism of abnormal microvascular function is not well understood. Hypothesis: A possible mechanism for the reduction in CFR may be that the microcirculation is already near maximal dilation in the basal state and is therefore limited in the ability to further dilate and compensate for the increase in myocardial demand. Methods: Eight patients with symptomatic HCM and eight age- and sex-matched controls were studied. All patients underwent coronary angiography and coronary hemodynamic assessment with an intracoronary Doppler wire to determine total coronary blood flow, coronary resistance, and coronary flow reserve (CFR). Phasic blood flow parameters were also obtained. Results: Compared with controls (n ⫽ 8), patients with HCM (n ⫽ 8) had higher coronary blood flow (52 ⫾ 19 versus 33 ⫾ 11 mL/min, P ⫽ 0.03), lower coronary resistance (2.12 ⫾ 0.91 versus 3.13 ⫾ 0.93 mm Hg/mL/min, P ⫽ 0.05), and lower CFR (2.1 ⫾ 0.7 versus 3.4 ⫾ 1.0 mm, P ⫽ 0.02). There was a direct correlation between CFR and coronary resistance (r ⫽ .5, P ⫽ .05). HCM patients also had abnormal phasic coronary flow characteristics with lower systolic velocities or reversal of flow during systole, and a more rapid deceleration of diastolic blood flow (40.7 ⫾ 13.2 versus 27.5 ⫾ 8.5 cm/sec2, P ⫽ .03). Conclusion: The reduction of CFR in HCM patients may be secondary to near maximal vasodilatation of the microcirculation in the basal state rather than narrowing of intramyocardial small arteries. Symptomatic HCM patients also have abnormal phasic coronary blood flow with a greater dependence on diastolic flow and a more rapid deceleration of diastolic blood flow.
End Systolic P (mmHg) LV End Diastolic P (mmHg) End Diastolic Volume (ul) Ejection Fraction (%) End systolic Stiffness (Ees, mmHg/ul) Diastolic stiffness β (mmHg/ul) Tau (ms) (logistic) mean ⫾ sem; *p ⬍ 0.05 vs SHAM
SHAM
BAND
59 ⫾ 3 ⫺1.5 ⫾ 0.9 16.4 ⫾ 1.1 66 ⫾ 3 8.5 ⫾ 1.3 0.111 ⫾ 0.021 5.1 ⫾ 0.2
69 ⫾ 3* 3.3 ⫾ 0.9* 15.5 ⫾ 1.1 63 ⫾ 3 18.4 ⫾ 3.5* 0.117 ⫾ 0.123 7.8 ⫾ 0.4*