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Significance of Postprandial Symptom Exacerbation in Hypertrophic Cardiomyopathy
Significance of Postprandial Symptom Exacerbation in Hypertrophic Cardiomyopathy Jonathon C. Adams, MDa, Steve R. Ommen, MDb, Kyle W. Klarich, MDb,*, A. Jamil Tajik, MDa, and Rick A. Nishimura, MDb Patients with hypertrophic cardiomyopathy (HC) can experience exacerbation of exertional symptoms after a meal. The present study was designed to determine the prevalence and clinical correlates of postprandial symptom exacerbation (PPSE) in patients with HC. The records of 558 patients with HC and PPSE data who had undergone echocardiography at our institution from 2002 to 2006 were reviewed. Continuous-wave Doppler velocities were used to determine the left ventricular outflow tract gradient. Left ventricular filling was assessed using transmitral velocity curves. The Minnesota Living With Heart Failure questionnaire was administered to measure symptom limitations. A multivariate regression model was developed to determine the independent correlates with PPSE. Of the 558 patients whose records were reviewed, 189 (33.8%) had PPSE. The patients with PPSE were more likely to experience New York Heart Association class III/IV dyspnea or presyncope. PPSE was associated with greater resting outflow gradients and lower perceived quality of life. In conclusion, patients presenting with severe postprandial symptoms and reduced quality of life should be carefully evaluated for the presence of dynamic left ventricular outflow tract obstruction. © 2010 Elsevier Inc. All rights reserved. (Am J Cardiol 2010;105:990 –992) It has been recognized that patients with hypertrophic cardiomyopathy (HC) can experience exacerbation of cardiac symptoms after a meal. Previous studies of relatively small patient populations have estimated that approximately 1/3 of patients with HC experience this phenomenon.1 The hemodynamic effects of a meal have been well documented for producing an arterial vasodilation with afterload reduction and a compensatory increase in heart rate.2–5 These changes, directly and indirectly, lead to worsening of left ventricular (LV) outflow tract obstruction and elevation of diastolic filling pressures. However, the postprandial response in patients with HC has been difficult to demonstrate,6,7 and the clinical implications of postprandial symptom exacerbation (PPSE) remain unclear. If PPSE implies labile obstruction to outflow, the clinical recognition of its presence would warrant consideration in diagnostic and therapeutic decision making. The aims of the present study were to determine the prevalence of PPSE in a large population of patients with HC, to determine the clinical correlates with PPSE that relate to disease severity, and to assess the effect of PPSE on quality of life (QOL) in patients with HC. Methods The Mayo Clinic Institutional Review Board approved the study. The Mayo Clinic Department of Cardiovascular a Division of Cardiovascular Diseases, Mayo Clinic, Scottsdale, Arizona; and bDivision of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota. Manuscript received August 6, 2009; revised manuscript received and accepted November 13, 2009. *Corresponding author. E-mail address: [email protected] (K.W. Klarich).
0002-9149/10/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2009.11.016
Disease has maintained a database of the clinical characteristics of all patients with HC evaluated at the clinic since 1959. The study was limited to all patients evaluated from 2002 to 2006 because tissue Doppler imaging had been phased in as a part of the standard echocardiographic evaluation at our institution in late 2001. All subjects for whom the symptomatic response to a meal was known were included. A graphic representation of the study population is shown in Figure 1. The clinical data for patients with HC were obtained from the Mayo Clinic HC database for the selected study period. The prevalence of PPSE was computed from all patients for whom the postprandial symptomatic response was known. Complete data for the analysis of clinical correlates with PPSE were available for a large subset of patients. The echocardiographic parameters included structural measurements and the resting LV outflow tract gradients derived from the continuous-wave Doppler velocities. A baseline comparison of the clinical and echocardiographic features of the study population was completed. Variables exhibiting a statistically significant difference on univariate analysis were entered into a logistic regression model to determine their independent association with PPSE. An assessment of LV filling was made from an analysis of the transmitral velocity profiles using the ratio of early transmitral flow velocity (E) to medial mitral annular tissue velocity (e=). The nominal E/e= value was compared between the PPSE-positive group and the PPSE-negative group, as was an E/e= value ⬎15, which has previously been correlated with elevated mean LV filling pressures.8 The Minnesota Living With Heart Failure questionnaire was administered to provide an objective measurement of the patients’ QOL. All patients who completed the questionnaire were included. The questionnaire includes a series www.AJConline.org
Cardiomyopathy/Postprandial Symptoms in Hypertrophic Cardiomyopathy
991
Table 2 Results of logistic regression model to determine independent clinical correlates with postprandial symptom exacerbation (PPSE)
Figure 1. Flow chart of study population. Table 1 Clinical features of study patients Characteristic
Mean age (years) Men Family history of sudden cardiac death Angina, New York Heart Association class III/IV Dyspnea, New York Heart Association class III/IV Presyncope Syncope Atrial fibrillation Hypertension Coronary artery disease Diabetes mellitus Mean ventricular septal thickness (mm) Ventricular septal thickness ⬎30 mm Left ventricular outflow tract gradient at rest (mm Hg) Mean 95% Confidence interval Obstruction at rest (left ventricular outflow tract or mid-ventricular) Left ventricular outflow tract gradient ⬎30 mm Hg at rest Mid-ventricular obstruction Left ventricular outflow tract gradient ⬎30 mm Hg with provocation only Nonobstructive Pacemaker Implantable cardioverterdefibrillator Myectomy Septal ablation Medications  Blocker Calcium channel blocker Disopyramide
PPSE
p Value
Yes (n ⫽ 182)
No (n ⫽ 355)
52 ⫾ 15 115 (63%) 33 (18%)
50 ⫾ 18 203 (57%) 68 (19%)
Correlate
p Value
Dyspnea, New York Heart Association class III/IV Presyncope Septal thickness Left ventricular outflow tract gradient at rest Left ventricular outflow tract gradient ⬎30 mm Hg at rest
⬍0.001 ⬍0.001 0.45 0.22 0.02
Table 3 Diastolic filling analysis of patients with hypertrophic cardiomyopathy (HC) with or without postprandial symptom exacerbation (PPSE) Variable
0.37 0.20 0.82
18 (10%)
25 (7%)
0.25
119 (65%)
124 (35%)
⬍0.001
130 (71%) 39 (21%) 31 (17%) 76 (42%) 26 (14%) 12 (7%) 21.6 ⫾ 8.5
148 (42%) 71 (20%) 57 (16%) 127 (36%) 41 (12%) 17 (5%) 20.4 ⫾ 6.2
⬍0.001 0.74 0.81 0.19 0.41 0.42 0.04
14 (8%)
25 (7%)
0.86 ⬍0.01
48.7 43.0–54.5 121 (66%)
37.1 32.7–41.5 181 (51%)
⬍0.001
119 (65%)
166 (47%)
⬍0.001
2 (1%) 36 (20%)
15 (4%) 72 (20%)
0.07 0.91
25 (14%) 25 (14%) 26 (14%)
102 (29%) 70 (20%) 65 (18%)
⬍0.001 0.10 0.28
61 (34%) 29 (16%)
113 (32%) 35 (10%)
0.70 0.05
129 (71%) 53 (29%) 14 (8%)
230 (65%) 99 (28%) 18 (5%)
0.18 0.76 0.25
of 20 statements related to cardiac-specific symptom limitation and has been previously validated.9,10 The scores from the individual statements were summed to achieve a total QOL score with a range from 0 to 100, with lower scores indicating less symptom limitation (ie, better QOL).
E/e= ratio Mean 95% Confidence interval E/e= ratio ⬎15
PPSE
p Value
Yes (n ⫽ 132)
No (n ⫽ 276)
17.3 16.0–18.7 68 (17%)
16.2 15.2–17.2 120 (29%)
0.04
0.14
E/e= ⫽ early transmitral flow velocity to medial mitral annular tissue velocity.
The scores from the completed questionnaires were compared between the PPSE-positive group and the PPSEnegative group to assess the effect of PPSE on QOL. All continuous variables were tested for normality of distribution. Ventricular septal thickness and resting LV outflow tract gradient data were normalized with a logarithmic transformation. The 2-tailed t test, Wilcoxon rank sum test, and Kruskal-Wallis test were used, as appropriate. Nominal data were analyzed using the 2-tailed Fisher exact test. A linear regression model was developed to determine the independent correlates with PPSE. A correlation coefficient was determined, and p values were calculated. The results are reported as the mean ⫾ SD, with 95% confidence intervals. Statistical significance was set, a priori, at p ⬍0.05. Results Of the 558 patients included in the present study, 189 (33.8%) reported PPSE. The clinical characteristics of a subset of 537 patients evaluated for clinical correlates with PPSE are summarized in Table 1. The results of the baseline comparison indicated that patients with PPSE were more likely to have New York Heart Association class III/IV dyspnea or presyncope, greater septal thickness, and greater resting LV outflow tract gradients. A logistic regression model was developed with the variables of statistical significance from the baseline comparison to assess their independent association with PPSE. The results of the regression model (Table 2) showed that patients with PPSE were more likely to have advanced dyspnea (p ⬍0.001) or presyncope (p ⬍0.001) and resting LV outflow tract gradients ⬎30 mm Hg (p ⫽ 0.02). The results of the diastolic filling assessment in the patients with HC and PPSE are summarized in Table 3. The nominal E/e= ratio was significantly greater statistically in
992
The American Journal of Cardiology (www.AJConline.org)
the patients with PPSE; however, the proportion of patients with an E/e= ratio ⬎15 was similar between the groups. The mean score from the Minnesota Living With Heart Failure questionnaire was 44 (95% confidence interval 40 to 48) for patients with PPSE and 29 (95% confidence interval 26 to 32) for those without PPSE. The difference was significant (p ⬍0.001). These findings were consistent with a lower perceived QOL in patients with HC and PPSE. Discussion The prevalence of PPSE in patients with HC on initial presentation was 33.8%. This percentage was similar to previous estimates of 37%1 and supports the observation that PPSE is frequently reported among patients with HC. From a large population of patients with HC, our results have shown that patients with HC and PPSE are more likely to report symptoms of advanced dyspnea or presyncope. These findings were not only identified on direct comparison of the clinical features between the PPSE-positive and PPSEnegative patients; they were also verified as independent correlates with PPSE on multivariate regression analysis. Although the present study was not designed to determine the pathophysiologic mechanism of PPSE, it is noteworthy that patients with PPSE were more likely to have LV outflow tract obstruction. In consideration of the postprandial hemodynamic response, the vasodilatory effect of a meal results in a decrease in afterload and directly exacerbates the severity of the obstruction. Likewise, the reflex increase in heart rate shortens the diastolic filling period, thereby reducing the preload (particularly in patients with mild to moderate diastolic dysfunction), which would further worsen the obstruction. In this sense, the act of eating a meal might represent a provocative hemodynamic maneuver in many patients with HC. Under the conditions of reduced LV volume and afterload, a patient would be predisposed to presyncope should an abrupt change in position occur. The present study identified a strong correlation between presyncope and PPSE, further supporting the notion that PPSE primarily represents dynamic LV outflow tract obstruction. The results of the present study were unable to show a clear relation between diastolic filling and PPSE. This result was not unexpected, because the assessment of diastolic filling is difficult in patients with HC.11 Furthermore, only the diastolic function parameters at rest were available for the present retrospective analysis, and these might not have been robust enough to predict what might occur with provocation. The present results have clearly shown that QOL was limited to a much greater degree in patients experiencing PPSE. The mean scores on the Minnesota Living With Heart Failure questionnaire were 52% greater for the patients reporting PPSE than for those who remained symptom free. This finding emphasizes the symptom limitations
common to patients with PPSE and is important to recognize on clinical evaluation. The present study was limited by its retrospective design and the restriction of the patient population to a single tertiary referral center. Also, the assessment of diastolic filling can be problematic, particularly in patients with HC.11 Nevertheless, the observations were consistent with previous reports of the prevalence and the known pathophysiologic mechanisms of dynamic LV outflow tract obstruction. In conclusion, PPSE can be reported by approximately 1/3 of patients with HC. The presence of PPSE in patients with HC was independently associated with greater resting LV outflow tract gradients and advanced clinical symptoms that limit QOL. These findings suggest that PPSE stems from hemodynamic changes that alter loading conditions on the left ventricle, worsening LV outflow tract obstruction. Therefore, patients presenting with severe PPSE and reduced QOL should be carefully evaluated for the presence of dynamic LV outflow tract obstruction. 1. Gilligan DM, Nihoyannopoulos P, Fletcher A, Sbarouni E, Dritsas A, Oakley CM. Symptoms of hypertrophic cardiomyopathy, with special emphasis on syncope and postprandial exacerbation of symptoms. Clin Cardiol 1996;19:371–378. 2. Fagan TC, Sawyer PR, Gourley LA, Lee JT, Gaffney TE. Postprandial alterations in hemodynamics and blood pressure in normal subjects. Am J Cardiol 1986;58:636 – 641. 3. Kelbaek H, Munck O, Christensen NJ, Godtfredsen J. Central haemodynamic changes after a meal. Br Heart J 1989;61:506 –509. 4. Packer M, Medina N, Yushak M. Hemodynamic changes mimicking a vasodilator drug response in the absence of drug therapy after right heart catheterization in patients with chronic heart failure. Circulation 1985;71:761–766. 5. Hoost U, Kelbaek H, Rasmusen H, Court-Payen M, Christensen NJ, Pedersen-Bjergaard U, Lorenzen T. Haemodynamic effects of eating: the role of meal composition. Clin Sci Lond 1996;90:269 –276. 6. Gilligan DM, Chan WL, Ang EL, Oakley CM. Effects of a meal on hemodynamic function at rest and during exercise in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 1991;18:429 – 436. 7. Gilligan DM, Marsonis A, Joshi J, Nihoyannopoulos P, Ghatei MA, Bloom SR, Oakley CM. Cardiovascular and hormonal responses to a meal in hypertrophic cardiomyopathy: a comparison of patients with and without postprandial exacerbation of symptoms. Clin Cardiol 1996;19:129 –135. 8. Ommen SR, Nishimura RA, Appleton CP, Miller FA, Oh JK, Redfield MM, Tajik AJ. Clinical utility of Doppler echocardiography and tissue Doppler imaging in the estimation of left ventricular filling pressures: a comparative simultaneous Doppler-catheterization study. Circulation 2000;102:1788 –1794. 9. Guyatt GH. Measurement of health-related quality of life in heart failure. J Am Coll Cardiol 1993;22:185A–191A. 10. Hak T, Willems D, van der Wal G, Visser F. A qualitative validation of the Minnesota living with heart failure questionnaire. Qual Life Res 2004;13:417– 426. 11. Geske JB, Sorajja P, Nishimura RA, Ommen SR. Evaluation of left ventricular filling pressures by Doppler echocardiography in patients with hypertrophic cardiomyopathy: correlation with direct left atrial pressure measurement at cardiac catheterization. Circulation 2007; 116:2702–2708.
0002-9149/10/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2009.11.016
Disease has maintained a database of the clinical characteristics of all patients with HC evaluated at the clinic since 1959. The study was limited to all patients evaluated from 2002 to 2006 because tissue Doppler imaging had been phased in as a part of the standard echocardiographic evaluation at our institution in late 2001. All subjects for whom the symptomatic response to a meal was known were included. A graphic representation of the study population is shown in Figure 1. The clinical data for patients with HC were obtained from the Mayo Clinic HC database for the selected study period. The prevalence of PPSE was computed from all patients for whom the postprandial symptomatic response was known. Complete data for the analysis of clinical correlates with PPSE were available for a large subset of patients. The echocardiographic parameters included structural measurements and the resting LV outflow tract gradients derived from the continuous-wave Doppler velocities. A baseline comparison of the clinical and echocardiographic features of the study population was completed. Variables exhibiting a statistically significant difference on univariate analysis were entered into a logistic regression model to determine their independent association with PPSE. An assessment of LV filling was made from an analysis of the transmitral velocity profiles using the ratio of early transmitral flow velocity (E) to medial mitral annular tissue velocity (e=). The nominal E/e= value was compared between the PPSE-positive group and the PPSE-negative group, as was an E/e= value ⬎15, which has previously been correlated with elevated mean LV filling pressures.8 The Minnesota Living With Heart Failure questionnaire was administered to provide an objective measurement of the patients’ QOL. All patients who completed the questionnaire were included. The questionnaire includes a series www.AJConline.org
Cardiomyopathy/Postprandial Symptoms in Hypertrophic Cardiomyopathy
991
Table 2 Results of logistic regression model to determine independent clinical correlates with postprandial symptom exacerbation (PPSE)
Figure 1. Flow chart of study population. Table 1 Clinical features of study patients Characteristic
Mean age (years) Men Family history of sudden cardiac death Angina, New York Heart Association class III/IV Dyspnea, New York Heart Association class III/IV Presyncope Syncope Atrial fibrillation Hypertension Coronary artery disease Diabetes mellitus Mean ventricular septal thickness (mm) Ventricular septal thickness ⬎30 mm Left ventricular outflow tract gradient at rest (mm Hg) Mean 95% Confidence interval Obstruction at rest (left ventricular outflow tract or mid-ventricular) Left ventricular outflow tract gradient ⬎30 mm Hg at rest Mid-ventricular obstruction Left ventricular outflow tract gradient ⬎30 mm Hg with provocation only Nonobstructive Pacemaker Implantable cardioverterdefibrillator Myectomy Septal ablation Medications  Blocker Calcium channel blocker Disopyramide
PPSE
p Value
Yes (n ⫽ 182)
No (n ⫽ 355)
52 ⫾ 15 115 (63%) 33 (18%)
50 ⫾ 18 203 (57%) 68 (19%)
Correlate
p Value
Dyspnea, New York Heart Association class III/IV Presyncope Septal thickness Left ventricular outflow tract gradient at rest Left ventricular outflow tract gradient ⬎30 mm Hg at rest
⬍0.001 ⬍0.001 0.45 0.22 0.02
Table 3 Diastolic filling analysis of patients with hypertrophic cardiomyopathy (HC) with or without postprandial symptom exacerbation (PPSE) Variable
0.37 0.20 0.82
18 (10%)
25 (7%)
0.25
119 (65%)
124 (35%)
⬍0.001
130 (71%) 39 (21%) 31 (17%) 76 (42%) 26 (14%) 12 (7%) 21.6 ⫾ 8.5
148 (42%) 71 (20%) 57 (16%) 127 (36%) 41 (12%) 17 (5%) 20.4 ⫾ 6.2
⬍0.001 0.74 0.81 0.19 0.41 0.42 0.04
14 (8%)
25 (7%)
0.86 ⬍0.01
48.7 43.0–54.5 121 (66%)
37.1 32.7–41.5 181 (51%)
⬍0.001
119 (65%)
166 (47%)
⬍0.001
2 (1%) 36 (20%)
15 (4%) 72 (20%)
0.07 0.91
25 (14%) 25 (14%) 26 (14%)
102 (29%) 70 (20%) 65 (18%)
⬍0.001 0.10 0.28
61 (34%) 29 (16%)
113 (32%) 35 (10%)
0.70 0.05
129 (71%) 53 (29%) 14 (8%)
230 (65%) 99 (28%) 18 (5%)
0.18 0.76 0.25
of 20 statements related to cardiac-specific symptom limitation and has been previously validated.9,10 The scores from the individual statements were summed to achieve a total QOL score with a range from 0 to 100, with lower scores indicating less symptom limitation (ie, better QOL).
E/e= ratio Mean 95% Confidence interval E/e= ratio ⬎15
PPSE
p Value
Yes (n ⫽ 132)
No (n ⫽ 276)
17.3 16.0–18.7 68 (17%)
16.2 15.2–17.2 120 (29%)
0.04
0.14
E/e= ⫽ early transmitral flow velocity to medial mitral annular tissue velocity.
The scores from the completed questionnaires were compared between the PPSE-positive group and the PPSEnegative group to assess the effect of PPSE on QOL. All continuous variables were tested for normality of distribution. Ventricular septal thickness and resting LV outflow tract gradient data were normalized with a logarithmic transformation. The 2-tailed t test, Wilcoxon rank sum test, and Kruskal-Wallis test were used, as appropriate. Nominal data were analyzed using the 2-tailed Fisher exact test. A linear regression model was developed to determine the independent correlates with PPSE. A correlation coefficient was determined, and p values were calculated. The results are reported as the mean ⫾ SD, with 95% confidence intervals. Statistical significance was set, a priori, at p ⬍0.05. Results Of the 558 patients included in the present study, 189 (33.8%) reported PPSE. The clinical characteristics of a subset of 537 patients evaluated for clinical correlates with PPSE are summarized in Table 1. The results of the baseline comparison indicated that patients with PPSE were more likely to have New York Heart Association class III/IV dyspnea or presyncope, greater septal thickness, and greater resting LV outflow tract gradients. A logistic regression model was developed with the variables of statistical significance from the baseline comparison to assess their independent association with PPSE. The results of the regression model (Table 2) showed that patients with PPSE were more likely to have advanced dyspnea (p ⬍0.001) or presyncope (p ⬍0.001) and resting LV outflow tract gradients ⬎30 mm Hg (p ⫽ 0.02). The results of the diastolic filling assessment in the patients with HC and PPSE are summarized in Table 3. The nominal E/e= ratio was significantly greater statistically in
992
The American Journal of Cardiology (www.AJConline.org)
the patients with PPSE; however, the proportion of patients with an E/e= ratio ⬎15 was similar between the groups. The mean score from the Minnesota Living With Heart Failure questionnaire was 44 (95% confidence interval 40 to 48) for patients with PPSE and 29 (95% confidence interval 26 to 32) for those without PPSE. The difference was significant (p ⬍0.001). These findings were consistent with a lower perceived QOL in patients with HC and PPSE. Discussion The prevalence of PPSE in patients with HC on initial presentation was 33.8%. This percentage was similar to previous estimates of 37%1 and supports the observation that PPSE is frequently reported among patients with HC. From a large population of patients with HC, our results have shown that patients with HC and PPSE are more likely to report symptoms of advanced dyspnea or presyncope. These findings were not only identified on direct comparison of the clinical features between the PPSE-positive and PPSEnegative patients; they were also verified as independent correlates with PPSE on multivariate regression analysis. Although the present study was not designed to determine the pathophysiologic mechanism of PPSE, it is noteworthy that patients with PPSE were more likely to have LV outflow tract obstruction. In consideration of the postprandial hemodynamic response, the vasodilatory effect of a meal results in a decrease in afterload and directly exacerbates the severity of the obstruction. Likewise, the reflex increase in heart rate shortens the diastolic filling period, thereby reducing the preload (particularly in patients with mild to moderate diastolic dysfunction), which would further worsen the obstruction. In this sense, the act of eating a meal might represent a provocative hemodynamic maneuver in many patients with HC. Under the conditions of reduced LV volume and afterload, a patient would be predisposed to presyncope should an abrupt change in position occur. The present study identified a strong correlation between presyncope and PPSE, further supporting the notion that PPSE primarily represents dynamic LV outflow tract obstruction. The results of the present study were unable to show a clear relation between diastolic filling and PPSE. This result was not unexpected, because the assessment of diastolic filling is difficult in patients with HC.11 Furthermore, only the diastolic function parameters at rest were available for the present retrospective analysis, and these might not have been robust enough to predict what might occur with provocation. The present results have clearly shown that QOL was limited to a much greater degree in patients experiencing PPSE. The mean scores on the Minnesota Living With Heart Failure questionnaire were 52% greater for the patients reporting PPSE than for those who remained symptom free. This finding emphasizes the symptom limitations
common to patients with PPSE and is important to recognize on clinical evaluation. The present study was limited by its retrospective design and the restriction of the patient population to a single tertiary referral center. Also, the assessment of diastolic filling can be problematic, particularly in patients with HC.11 Nevertheless, the observations were consistent with previous reports of the prevalence and the known pathophysiologic mechanisms of dynamic LV outflow tract obstruction. In conclusion, PPSE can be reported by approximately 1/3 of patients with HC. The presence of PPSE in patients with HC was independently associated with greater resting LV outflow tract gradients and advanced clinical symptoms that limit QOL. These findings suggest that PPSE stems from hemodynamic changes that alter loading conditions on the left ventricle, worsening LV outflow tract obstruction. Therefore, patients presenting with severe PPSE and reduced QOL should be carefully evaluated for the presence of dynamic LV outflow tract obstruction. 1. Gilligan DM, Nihoyannopoulos P, Fletcher A, Sbarouni E, Dritsas A, Oakley CM. Symptoms of hypertrophic cardiomyopathy, with special emphasis on syncope and postprandial exacerbation of symptoms. Clin Cardiol 1996;19:371–378. 2. Fagan TC, Sawyer PR, Gourley LA, Lee JT, Gaffney TE. Postprandial alterations in hemodynamics and blood pressure in normal subjects. Am J Cardiol 1986;58:636 – 641. 3. Kelbaek H, Munck O, Christensen NJ, Godtfredsen J. Central haemodynamic changes after a meal. Br Heart J 1989;61:506 –509. 4. Packer M, Medina N, Yushak M. Hemodynamic changes mimicking a vasodilator drug response in the absence of drug therapy after right heart catheterization in patients with chronic heart failure. Circulation 1985;71:761–766. 5. Hoost U, Kelbaek H, Rasmusen H, Court-Payen M, Christensen NJ, Pedersen-Bjergaard U, Lorenzen T. Haemodynamic effects of eating: the role of meal composition. Clin Sci Lond 1996;90:269 –276. 6. Gilligan DM, Chan WL, Ang EL, Oakley CM. Effects of a meal on hemodynamic function at rest and during exercise in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 1991;18:429 – 436. 7. Gilligan DM, Marsonis A, Joshi J, Nihoyannopoulos P, Ghatei MA, Bloom SR, Oakley CM. Cardiovascular and hormonal responses to a meal in hypertrophic cardiomyopathy: a comparison of patients with and without postprandial exacerbation of symptoms. Clin Cardiol 1996;19:129 –135. 8. Ommen SR, Nishimura RA, Appleton CP, Miller FA, Oh JK, Redfield MM, Tajik AJ. Clinical utility of Doppler echocardiography and tissue Doppler imaging in the estimation of left ventricular filling pressures: a comparative simultaneous Doppler-catheterization study. Circulation 2000;102:1788 –1794. 9. Guyatt GH. Measurement of health-related quality of life in heart failure. J Am Coll Cardiol 1993;22:185A–191A. 10. Hak T, Willems D, van der Wal G, Visser F. A qualitative validation of the Minnesota living with heart failure questionnaire. Qual Life Res 2004;13:417– 426. 11. Geske JB, Sorajja P, Nishimura RA, Ommen SR. Evaluation of left ventricular filling pressures by Doppler echocardiography in patients with hypertrophic cardiomyopathy: correlation with direct left atrial pressure measurement at cardiac catheterization. Circulation 2007; 116:2702–2708.