© 2015, Wiley Periodicals, Inc. DOI: 10.1111/echo.12951
Echocardiography
Postprandial Hemodynamics in Hypertrophic Cardiomyopathy Jonathon C. Adams, M.D.,* John P. Bois, M.D.,† Mitsuru Masaki, M.D.,† Toshinori Yuasa, M.D.,† Jae K. Oh, M.D.,† Steve R. Ommen, M.D.,† Rick A. Nishimura, M.D.,† and Kyle W. Klarich, M.D.† *Division of Cardiovascular Diseases, Mayo Clinic, Scottsdale, Arizona; and †Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota
Objectives: Prior analysis at our institution found that patients with hypertrophic cardiomyopathy (HCM) who experience postprandial symptoms (PPS) are more likely to have resting left ventricular outflow tract (LVOT) obstruction and reduced quality of life. Our objective was to determine whether PPS in patients with HCM vs healthy subjects occur as a result of measurable hemodynamic alterations in the postprandial hemodynamic response. Methods: We conducted a prospective cross-sectional study examining 45 patients with HCM and 10 controls who underwent fasting and postprandial 2-dimensional Doppler echocardiography. Postprandial echocardiographic measurements were obtained at symptom onset or 30 minutes after consumption of a standardized meal, whichever occurred first. Results: The HCM population included 18 (40%) patients with PPS and 27 (60%) without PPS. Compared to controls, mean resting peak LVOT gradient was 23.4 17.6 mmHg in HCM patients with PPS and 25.1 33.1 mmHg in those without PPS (P = 0.10). The mean change in peak LVOT gradient after a meal was 0.7 1.1 mmHg for controls, 5.0 8.3 mmHg for HCM patients with PPS, and 1.5 18.2 mmHg for HCM patients without PPS (P = 0.64). Conclusion: Although the ability to provoke an increased LVOT gradient with a postprandial, upright exercise study protocol was recently reported, the current study suggests that a resting, supine, postprandial protocol does not elicit evidence of LVOT obstruction. Therefore, future investigations should consider whether simply performing an upright postprandial study in HCM patients with PPS will provide evidence of dynamic LVOT or if the addition of an exercise component is necessary. (Echocardiography 2015;32:1614–1620) Key words: echocardiography, hypertrophic cardiomyopathy, left ventricular outflow tract obstruction Approximately one-third of patients with hypertrophic cardiomyopathy (HCM) may experience postprandial exacerbation of cardiac symptoms, such as dyspnea, palpitations, and presyncope.1,2 The hemodynamic effects of a meal have been well documented as producing arterial vasodilation, with afterload reduction and a compensatory increase in heart rate.3–6 These changes, directly and indirectly, lead to worsening of left ventricular (LV) outflow tract (LVOT) obstruction and elevation of diastolic filling pressures. Patients with HCM who report exacerbation of postprandial symptoms (PPS) are more likely to have moderate or severe dyspnea and presyncope, and poorer quality of life compared with patients with HCM who do not experience PPS.1 In addition, patients with PPS are more likely to have resting LVOT obstruction.1 These findings suggest that HCM patients with PPS may have more dynamic disease such that changes in LV loading conditions that occur as a Address for correspondence and reprint requests: Kyle W. Klarich, M.D., Division of Cardiovascular Diseases, Mayo Clinic, 200 First St SW, Rochester, MN 55905. Fax: 507-284-3968; E-mail: [email protected]
1614
result of consuming a meal may be sufficient to provoke LVOT obstruction. Nevertheless, definitively demonstrating the mechanism of PPS in HCM has been challenging7,8 and remains unproven. The objectives of this study were to assess the postprandial hemodynamic response in patients with HCM compared with normal subjects and to identify specific hemodynamic derangements that occur in HCM patients with PPS compared with those who remain asymptomatic after a meal. Methods: The Mayo Clinic Institutional Review Board approved the study. The study used a prospective, cross-sectional design that included patients with HCM aged 18 or older who were scheduled for initial evaluation at the Mayo Cardiomyopathy Clinic. Exclusion criteria included food allergy, coronary artery disease, a history of septal reduction therapy, and pregnancy. The control group comprised 10 age- and sex-matched volunteers who were statistically similar in age and sex to the study population and who had no history of cardiac disease.
Postprandial Symptoms in HCM
Participation in the study was voluntary. Patients were contacted by telephone and mailed a cover letter prior to their clinic appointment explaining the objectives of the study and offering enrollment. Those who were interested in study participation contacted the study coordinators and were screened for inclusion and exclusion criteria. Financial support for the study was provided by the Mayo Foundation Small Grants Program. Upon arrival at the clinic, participants met with a clinical assistant from the Mayo Cardiomyopathy Clinic; at which time, verbal informed consent was obtained and baseline demographics and clinical history were obtained. The patients proceeded to the echocardiography laboratory, and fasting comprehensive 2-dimensional Doppler echocardiography (Siemens, Malvern, PA, USA; Philips, Andover, MA, USA; GE, Waukesh, WI, USA) studies were performed, including measurement of LVOT gradient at rest and with the Valsalva maneuver, mitral valve assessments, and diastolic function analysis. LV wall thickness and chamber dimensions were measured in the left parasternal long-axis view, and LV ejection fraction was determined by the 2-dimensional modified Quinones method. LVOT maximum velocity was obtained, and the peak LVOT gradient was estimated by the modified Bernoulli equation. In collaboration with staff from the Department of Gastroenterology, we had a standardized meal prepared that had previously been shown to induce hemodynamic changes.8 The meal consisted of 1 boiled egg (70 g), 2 bread rolls (120 g), a grilled chicken breast (40 g), margarine (20 g), cheese (40 g), and orange juice (200 mL) totaling 740 calories, with 17% protein, 41% fat, and 42% carbohydrates. After completion of this meal, the patient was monitored for evidence of PPS. Echocardiographic measurements were repeated at onset of symptoms or at 30 minutes after completion of the meal for those who remained asymptomatic. A 30-minute time period was used, given prior physiologic studies demonstrating that maximal postprandial superior mesenteric artery blood flow occurs between 20 and 40 minutes after a meal.9 Sonographers were blinded to the historical PPS status of the patient, and all echocardiographic images and measurements were interpreted by the echocardiography research fellow, as well as by a staff physician. Baseline characteristics and hemodynamic measurements were summarized as mean and SD for continuous variables or as counts and percentages for categorical variables. Differences in hemodynamic parameters were calculated by subtracting fasting measurements from the corre-
sponding postprandial measurements. Parameters were summarized separately by patient group and by time period of measurement. Groups were compared using analysis of variance methods. Because the primary area of interest was pairwise comparison of individual patient groups, these comparisons were made using the chi-square test or the 2-sample t test, as appropriate. SAS statistical software (version 9.1; SAS Institute Inc., Cary, NC, USA) was used for analysis, and statistical significance was set at P ≤ 0.05. Results: The study population included 45 patients with HCM (67% men; mean age, 55.8 14.0 years) and 10 healthy volunteers (50% men; mean age, 49.8 8.3 years). Eighteen (40%) of the patients with HCM reported a history of PPS. With few exceptions, the clinical characteristics of patients with HCM and controls were comparable (Table I). Overall, patients with HCM had a higher body mass index (BMI [weight in kilograms divided by height in meters squared {kg/m2}]) and were more likely than healthy volunteers to be taking bblockers or calcium channel blockers. Patients with HCM who did not report PPS were slightly older and had a higher prevalence of hypertension, whereas HCM patients with a history of PPS were more likely to have a pacemaker or implantable cardioverter–defibrillator. By design, healthy volunteers had no history of cardiovascular symptoms. Among HCM patients, those with vs without a history of PPS more frequently reported angina, dyspnea, and/or presyncope. Baseline (fasting) echocardiographic measurements are listed in Table II. Mean septal thickness was 9.7 1.5 mm for controls, 18.5 2.9 mm for HCM patients with PPS, and 18.8 3.8 mm for HCM patients without PPS (comparison among all 3 groups, P < 0.001). Compared to controls, the HCM population had thicker posterior LV walls, higher LV ejection fraction, and a greater resting LVOT velocity. No difference in resting LVOT gradient was observed among HCM patients with or without a history of PPS. No significant changes in overall blood pressure or heart rate occurred after the standardized meal. Symptoms were observed in only 2 of the 45 (4%) patients with HCM. Both patients reported a clinical history of PPS, moderate dyspnea, and presyncope. LV septal thicknesses were 14 mm and 22 mm. The postprandial LVOT gradient was unchanged in 1 patient and increased from 30 mmHg to 32 mmHg in 1 patient. The mean resting peak LVOT gradient was 23.4 17.6 mmHg in HCM patients with PPS and 25.1 33.1 mmHg in those without PPS (P = 0.10). The mean change in peak LVOT gradient after a meal was 0.7 1.1 mmHg for 1615
Adams, et al.
TABLE I Baseline Characteristics
Variable Male sex Age, mean (SD), y BMI, mean (SD) Pacemaker/ICD Angina Class I Class II Class III Unknown Angina Class I Class II/III Dyspnea Class I Class II Class III Unknown Palpitations Presyncope Syncope PAF/AF Stroke Hypertension Diabetes mellitus Thyroid COPD/asthma Upper GI disease b-Blocker Calcium channel blocker Disopyramide ACE/ARB Diuretic
Normal* (n = 10) 5 (50) 49.8 (8.3) 26.6 (2.8) 0 (0) 10 (100) 0 (0) 0 (0) 0 (0) 10 (100) 0 (0) 10 (100) 0 (0) 0 (0) 0 (0) 2 (20) 1 (10) 0 (0) 0 (0) 0 (0) 1 (10) 1 (10) 1 (10) 0 (0) 2 (20) 0 (0) 0 (0) 0 (0) 2 (20) 1 (10)
HCM PPS+* (n = 18) 13 (72) 52.5 (15.0) 29.6 (4.1) 6 (33)
HCM PPS* (n = 27) 17 (63) 59.1 (13.0) 30.7 (4.9) 5 (19)
P-Value (Overall)
P-Value (Normal vs HCM PPS+)
P-Value (Normal vs HCM PPS)
P-Value (HCM PPS+ vs HCM PPS)
0.50 0.09 0.05 0.08 0.12
0.24 0.60 0.05 0.03 0.10
0.48 0.04 0.02 0.14 0.44
0.52 0.12 0.46 0.21 0.12
0.02
0.02
0.20
0.049
10 (56) 2 (11) 5 (28) 1 (6) (n = 17) 10 (59) 7 (41) (n = 18) 6 (33) 4 (22) 6 (33) 2 (11) 2 (11) 13 (72) 4 (22) 2 (11) 0 (0) 5 (28) 0 (0) 3 (17) 0 (0) 0 (0) 14 (78) 7 (39)
23 (85) 2 (7) 2 (7) 0 (0)
0.01
0.009
0.20
0.03
20 (74) 4 (15) 3 (11) 0 (0) 4 (15) 4 (15) 5 (19) 4 (15) 3 (11) 14 (52) 3 (11) 2 (7) 3 (11) 4 (15) 21 (78) 8 (30)
0.81 0.99 0.06 15, no. (%) Deceleration time, ms
Normal* (n = 10)
HCM PPS+* (n = 18)
HCM PPS* (n = 27)
P-Value (Overall)
P-Value (Normal vs HCM PPS+)
P-Value (Normal vs HCM PPS)
P-Value (HCM PPS+ vs HCM PPS)
31.1 (4.9) 43.5 (3.7) 9.7 (1.5) 7.5 (1.0) 65 (4.0) 1.1 (0.1) 5.2 (1.0) 0 (0)
27.4 (8.2) 40.6 (8.2) 18.5 (2.9) 11.9 (3.6) 72 (5.5) 2.1 (0.9) 23.4 (17.6) 5 (28)
308 (9.2) 43.5 (11.0) 18.8 (3.8) 11.3 (3.9) 71 (6.9) 1.9 (1.1) 25.1 (33.1) 7 (26)
0.34 0.55
Echocardiography
Postprandial Hemodynamics in Hypertrophic Cardiomyopathy Jonathon C. Adams, M.D.,* John P. Bois, M.D.,† Mitsuru Masaki, M.D.,† Toshinori Yuasa, M.D.,† Jae K. Oh, M.D.,† Steve R. Ommen, M.D.,† Rick A. Nishimura, M.D.,† and Kyle W. Klarich, M.D.† *Division of Cardiovascular Diseases, Mayo Clinic, Scottsdale, Arizona; and †Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota
Objectives: Prior analysis at our institution found that patients with hypertrophic cardiomyopathy (HCM) who experience postprandial symptoms (PPS) are more likely to have resting left ventricular outflow tract (LVOT) obstruction and reduced quality of life. Our objective was to determine whether PPS in patients with HCM vs healthy subjects occur as a result of measurable hemodynamic alterations in the postprandial hemodynamic response. Methods: We conducted a prospective cross-sectional study examining 45 patients with HCM and 10 controls who underwent fasting and postprandial 2-dimensional Doppler echocardiography. Postprandial echocardiographic measurements were obtained at symptom onset or 30 minutes after consumption of a standardized meal, whichever occurred first. Results: The HCM population included 18 (40%) patients with PPS and 27 (60%) without PPS. Compared to controls, mean resting peak LVOT gradient was 23.4 17.6 mmHg in HCM patients with PPS and 25.1 33.1 mmHg in those without PPS (P = 0.10). The mean change in peak LVOT gradient after a meal was 0.7 1.1 mmHg for controls, 5.0 8.3 mmHg for HCM patients with PPS, and 1.5 18.2 mmHg for HCM patients without PPS (P = 0.64). Conclusion: Although the ability to provoke an increased LVOT gradient with a postprandial, upright exercise study protocol was recently reported, the current study suggests that a resting, supine, postprandial protocol does not elicit evidence of LVOT obstruction. Therefore, future investigations should consider whether simply performing an upright postprandial study in HCM patients with PPS will provide evidence of dynamic LVOT or if the addition of an exercise component is necessary. (Echocardiography 2015;32:1614–1620) Key words: echocardiography, hypertrophic cardiomyopathy, left ventricular outflow tract obstruction Approximately one-third of patients with hypertrophic cardiomyopathy (HCM) may experience postprandial exacerbation of cardiac symptoms, such as dyspnea, palpitations, and presyncope.1,2 The hemodynamic effects of a meal have been well documented as producing arterial vasodilation, with afterload reduction and a compensatory increase in heart rate.3–6 These changes, directly and indirectly, lead to worsening of left ventricular (LV) outflow tract (LVOT) obstruction and elevation of diastolic filling pressures. Patients with HCM who report exacerbation of postprandial symptoms (PPS) are more likely to have moderate or severe dyspnea and presyncope, and poorer quality of life compared with patients with HCM who do not experience PPS.1 In addition, patients with PPS are more likely to have resting LVOT obstruction.1 These findings suggest that HCM patients with PPS may have more dynamic disease such that changes in LV loading conditions that occur as a Address for correspondence and reprint requests: Kyle W. Klarich, M.D., Division of Cardiovascular Diseases, Mayo Clinic, 200 First St SW, Rochester, MN 55905. Fax: 507-284-3968; E-mail: [email protected]
1614
result of consuming a meal may be sufficient to provoke LVOT obstruction. Nevertheless, definitively demonstrating the mechanism of PPS in HCM has been challenging7,8 and remains unproven. The objectives of this study were to assess the postprandial hemodynamic response in patients with HCM compared with normal subjects and to identify specific hemodynamic derangements that occur in HCM patients with PPS compared with those who remain asymptomatic after a meal. Methods: The Mayo Clinic Institutional Review Board approved the study. The study used a prospective, cross-sectional design that included patients with HCM aged 18 or older who were scheduled for initial evaluation at the Mayo Cardiomyopathy Clinic. Exclusion criteria included food allergy, coronary artery disease, a history of septal reduction therapy, and pregnancy. The control group comprised 10 age- and sex-matched volunteers who were statistically similar in age and sex to the study population and who had no history of cardiac disease.
Postprandial Symptoms in HCM
Participation in the study was voluntary. Patients were contacted by telephone and mailed a cover letter prior to their clinic appointment explaining the objectives of the study and offering enrollment. Those who were interested in study participation contacted the study coordinators and were screened for inclusion and exclusion criteria. Financial support for the study was provided by the Mayo Foundation Small Grants Program. Upon arrival at the clinic, participants met with a clinical assistant from the Mayo Cardiomyopathy Clinic; at which time, verbal informed consent was obtained and baseline demographics and clinical history were obtained. The patients proceeded to the echocardiography laboratory, and fasting comprehensive 2-dimensional Doppler echocardiography (Siemens, Malvern, PA, USA; Philips, Andover, MA, USA; GE, Waukesh, WI, USA) studies were performed, including measurement of LVOT gradient at rest and with the Valsalva maneuver, mitral valve assessments, and diastolic function analysis. LV wall thickness and chamber dimensions were measured in the left parasternal long-axis view, and LV ejection fraction was determined by the 2-dimensional modified Quinones method. LVOT maximum velocity was obtained, and the peak LVOT gradient was estimated by the modified Bernoulli equation. In collaboration with staff from the Department of Gastroenterology, we had a standardized meal prepared that had previously been shown to induce hemodynamic changes.8 The meal consisted of 1 boiled egg (70 g), 2 bread rolls (120 g), a grilled chicken breast (40 g), margarine (20 g), cheese (40 g), and orange juice (200 mL) totaling 740 calories, with 17% protein, 41% fat, and 42% carbohydrates. After completion of this meal, the patient was monitored for evidence of PPS. Echocardiographic measurements were repeated at onset of symptoms or at 30 minutes after completion of the meal for those who remained asymptomatic. A 30-minute time period was used, given prior physiologic studies demonstrating that maximal postprandial superior mesenteric artery blood flow occurs between 20 and 40 minutes after a meal.9 Sonographers were blinded to the historical PPS status of the patient, and all echocardiographic images and measurements were interpreted by the echocardiography research fellow, as well as by a staff physician. Baseline characteristics and hemodynamic measurements were summarized as mean and SD for continuous variables or as counts and percentages for categorical variables. Differences in hemodynamic parameters were calculated by subtracting fasting measurements from the corre-
sponding postprandial measurements. Parameters were summarized separately by patient group and by time period of measurement. Groups were compared using analysis of variance methods. Because the primary area of interest was pairwise comparison of individual patient groups, these comparisons were made using the chi-square test or the 2-sample t test, as appropriate. SAS statistical software (version 9.1; SAS Institute Inc., Cary, NC, USA) was used for analysis, and statistical significance was set at P ≤ 0.05. Results: The study population included 45 patients with HCM (67% men; mean age, 55.8 14.0 years) and 10 healthy volunteers (50% men; mean age, 49.8 8.3 years). Eighteen (40%) of the patients with HCM reported a history of PPS. With few exceptions, the clinical characteristics of patients with HCM and controls were comparable (Table I). Overall, patients with HCM had a higher body mass index (BMI [weight in kilograms divided by height in meters squared {kg/m2}]) and were more likely than healthy volunteers to be taking bblockers or calcium channel blockers. Patients with HCM who did not report PPS were slightly older and had a higher prevalence of hypertension, whereas HCM patients with a history of PPS were more likely to have a pacemaker or implantable cardioverter–defibrillator. By design, healthy volunteers had no history of cardiovascular symptoms. Among HCM patients, those with vs without a history of PPS more frequently reported angina, dyspnea, and/or presyncope. Baseline (fasting) echocardiographic measurements are listed in Table II. Mean septal thickness was 9.7 1.5 mm for controls, 18.5 2.9 mm for HCM patients with PPS, and 18.8 3.8 mm for HCM patients without PPS (comparison among all 3 groups, P < 0.001). Compared to controls, the HCM population had thicker posterior LV walls, higher LV ejection fraction, and a greater resting LVOT velocity. No difference in resting LVOT gradient was observed among HCM patients with or without a history of PPS. No significant changes in overall blood pressure or heart rate occurred after the standardized meal. Symptoms were observed in only 2 of the 45 (4%) patients with HCM. Both patients reported a clinical history of PPS, moderate dyspnea, and presyncope. LV septal thicknesses were 14 mm and 22 mm. The postprandial LVOT gradient was unchanged in 1 patient and increased from 30 mmHg to 32 mmHg in 1 patient. The mean resting peak LVOT gradient was 23.4 17.6 mmHg in HCM patients with PPS and 25.1 33.1 mmHg in those without PPS (P = 0.10). The mean change in peak LVOT gradient after a meal was 0.7 1.1 mmHg for 1615
Adams, et al.
TABLE I Baseline Characteristics
Variable Male sex Age, mean (SD), y BMI, mean (SD) Pacemaker/ICD Angina Class I Class II Class III Unknown Angina Class I Class II/III Dyspnea Class I Class II Class III Unknown Palpitations Presyncope Syncope PAF/AF Stroke Hypertension Diabetes mellitus Thyroid COPD/asthma Upper GI disease b-Blocker Calcium channel blocker Disopyramide ACE/ARB Diuretic
Normal* (n = 10) 5 (50) 49.8 (8.3) 26.6 (2.8) 0 (0) 10 (100) 0 (0) 0 (0) 0 (0) 10 (100) 0 (0) 10 (100) 0 (0) 0 (0) 0 (0) 2 (20) 1 (10) 0 (0) 0 (0) 0 (0) 1 (10) 1 (10) 1 (10) 0 (0) 2 (20) 0 (0) 0 (0) 0 (0) 2 (20) 1 (10)
HCM PPS+* (n = 18) 13 (72) 52.5 (15.0) 29.6 (4.1) 6 (33)
HCM PPS* (n = 27) 17 (63) 59.1 (13.0) 30.7 (4.9) 5 (19)
P-Value (Overall)
P-Value (Normal vs HCM PPS+)
P-Value (Normal vs HCM PPS)
P-Value (HCM PPS+ vs HCM PPS)
0.50 0.09 0.05 0.08 0.12
0.24 0.60 0.05 0.03 0.10
0.48 0.04 0.02 0.14 0.44
0.52 0.12 0.46 0.21 0.12
0.02
0.02
0.20
0.049
10 (56) 2 (11) 5 (28) 1 (6) (n = 17) 10 (59) 7 (41) (n = 18) 6 (33) 4 (22) 6 (33) 2 (11) 2 (11) 13 (72) 4 (22) 2 (11) 0 (0) 5 (28) 0 (0) 3 (17) 0 (0) 0 (0) 14 (78) 7 (39)
23 (85) 2 (7) 2 (7) 0 (0)
0.01
0.009
0.20
0.03
20 (74) 4 (15) 3 (11) 0 (0) 4 (15) 4 (15) 5 (19) 4 (15) 3 (11) 14 (52) 3 (11) 2 (7) 3 (11) 4 (15) 21 (78) 8 (30)
0.81 0.99 0.06 15, no. (%) Deceleration time, ms
Normal* (n = 10)
HCM PPS+* (n = 18)
HCM PPS* (n = 27)
P-Value (Overall)
P-Value (Normal vs HCM PPS+)
P-Value (Normal vs HCM PPS)
P-Value (HCM PPS+ vs HCM PPS)
31.1 (4.9) 43.5 (3.7) 9.7 (1.5) 7.5 (1.0) 65 (4.0) 1.1 (0.1) 5.2 (1.0) 0 (0)
27.4 (8.2) 40.6 (8.2) 18.5 (2.9) 11.9 (3.6) 72 (5.5) 2.1 (0.9) 23.4 (17.6) 5 (28)
308 (9.2) 43.5 (11.0) 18.8 (3.8) 11.3 (3.9) 71 (6.9) 1.9 (1.1) 25.1 (33.1) 7 (26)
0.34 0.55
