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Comparison of right and left ventricular responses to left ventricular assist device support in patients with severe heart failure. A primary role of mechanical unloading underlying reverse remodeling
Heart Failure/Transplant
Comparison of Right and Left Ventricular Responses to Left Ventricular Assist Device Support in Patients With Severe Heart Failure. A Primary Role of Mechanical Unloading Underlying Reverse Remodeling
Abstracts
Barbone A, Holmes JW, Heerdt PM, et al. Circulation 2001;104: 670 –5.
Development of Left Ventricular Hypertrophy in Adults With Hypertrophic Cardiomyopathy Caused by Cardiac Myosin-Binding Protein C Gene Mutations
Study Question: Left ventricular Assist devices (LVAD) reverse ventricular, myocardial and systemic abnormalities characteristic of severe heart failure (reverse remodeling). The relative contributions of hemodynamic unloading and normalized biochemical milieu to reverse remodeling are unknown. Methods and Results: Structural and functional characteristics were measured from 53 hearts of patients undergoing LVAD support (range, 8 to 360 days). Compared with medical support alone, patients receiving LVAD support for ⱖ30 days had higher central venous pressures, lower pulmonary artery diastolic pressures and higher cardiac outputs. In LVAD vs. transplantation hearts, V30 (ex vivo ventricular volume yielding passive ventricular pressure of 30 mm Hg) volume was decreased in the left ventricle (LV) (179⫾75 vs. 261⫾118 mL, p⫽0.005) but not in the right ventricle (RV) (140⫾59 vs. 48⫾52 mL, p⫽NS). LV myocyte diameter decreased more significantly after LVAD support (17%, p⫽0.05) than in the RV (11%, p⫽NS). Compared with transplantation, LVAD support increased normalized sarcoplasmic reticular calcium ATPase in the LV (0.51⫾0.26 vs. 1.04⫾0.34, p⬍0.001) but not in the RV (0.48⫾34 vs. 0.67⫾0.55, p⫽NS). Finally, LVAD support improved force-frequency relations of isolated superfused LV trabeculae (p⫽0.01) but not RV trabeculae. Conclusion: Reduction of hemodynamic load is a primary factor underlying several important features of reverse remodeling. These findings do not preclude a possible primary role of neurohormonal factors underlying other facets of reverse remodeling during LVAD support. Perspective: These findings provide valuable insights into the myocardial responses to mechanical ventricular unloading. The different hemodynamic characteristics of the right and left ventricle suggest a strong role for hemodynamic differences. The authors acknowledge other potential factors, but such factors are unlikely to yield a profound right-vs.-left ventricular differential effect. RC
Maron BJ, Niimura H, Casey SA, et al. J Am Coll Cardiol 2001; 38:315–21. Study Question: The authors evaluated whether left ventricular hypertrophy (LVH) can be demonstrated during adulthood in genetically affected relatives with hypertrophic cardiomyopathy (HCM). Hypertrophic cardiomyopathy is a heterogeneous cardiac disease caused by mutations in nine genes that encode proteins of the sarcomere. Mutations in cardiac myosin-binding protein C (MyBPC) gene have been associated with age-related penetrance. Methods and Results: As part of an evaluation of LVH in patients with HCM, the authors studied the phenotypic expression caused by MyBPC mutations in seven genotyped pedigrees. They utilized echocardiography and 12-lead electrocardiography. Of 119 family members studied, 61 were identified with a MyBPC mutation, including 21 genetically affected relatives (34%) who did not express the HCM morphologic phenotype (by virtue of showing normal left ventricular wall thickness). Of these 21 phenotype-negative individuals, nine were children, presumably in the prehypertrophic phase, and 12 were adults. Of the 12 adults with normal wall thickness ⱕ12 mm (seven also with normal electrocardiograms), five underwent serial evaluation, over 4 – 6 years. Three of these five adults developed LVH in mid life, appearing for the first time at 33, 34 and 42 years of age, respectively, not associated with outflow obstruction or significant symptoms. Conclusion: In adults with HCM, disease-causing MyBPC mutations are not uncommonly associated with absence of LVH on echocardiogram. Delayed remodeling with the development of LVH appearing de novo in adulthood, substantiates the principle of age-related penetrance for MyBPC mutations in HCM. These observations challenge prevailing perceptions regarding the HCM clinical spectrum and family screening strategies and further characterize the evolution of LVH in this disease. Perspective: Although a relatively small cohort, these are carefully conducted studies, and the conclusions of the authors are substantiated by their data. The observations provide further evidence that knowledge of the specific genetic mutations in cardiomyopathy will help determine the most effective screening strategy for families affected. RC
Plasma Nitric Oxide Level in Heart Failure Secondary to Left Ventricular Diastolic Dysfunction Yu CM, Fung PCW, Chan G, Lai HWH, Wang Q, Lau CP. Am J Cardiol 2001;88:867–70. Study Question: Nitric oxide (NO) is a free radical that is elevated in the plasma of patients with systolic heart failure.
ACC CURRENT JOURNAL REVIEW Jan/Feb 2002
51
Comparison of Right and Left Ventricular Responses to Left Ventricular Assist Device Support in Patients With Severe Heart Failure. A Primary Role of Mechanical Unloading Underlying Reverse Remodeling
Abstracts
Barbone A, Holmes JW, Heerdt PM, et al. Circulation 2001;104: 670 –5.
Development of Left Ventricular Hypertrophy in Adults With Hypertrophic Cardiomyopathy Caused by Cardiac Myosin-Binding Protein C Gene Mutations
Study Question: Left ventricular Assist devices (LVAD) reverse ventricular, myocardial and systemic abnormalities characteristic of severe heart failure (reverse remodeling). The relative contributions of hemodynamic unloading and normalized biochemical milieu to reverse remodeling are unknown. Methods and Results: Structural and functional characteristics were measured from 53 hearts of patients undergoing LVAD support (range, 8 to 360 days). Compared with medical support alone, patients receiving LVAD support for ⱖ30 days had higher central venous pressures, lower pulmonary artery diastolic pressures and higher cardiac outputs. In LVAD vs. transplantation hearts, V30 (ex vivo ventricular volume yielding passive ventricular pressure of 30 mm Hg) volume was decreased in the left ventricle (LV) (179⫾75 vs. 261⫾118 mL, p⫽0.005) but not in the right ventricle (RV) (140⫾59 vs. 48⫾52 mL, p⫽NS). LV myocyte diameter decreased more significantly after LVAD support (17%, p⫽0.05) than in the RV (11%, p⫽NS). Compared with transplantation, LVAD support increased normalized sarcoplasmic reticular calcium ATPase in the LV (0.51⫾0.26 vs. 1.04⫾0.34, p⬍0.001) but not in the RV (0.48⫾34 vs. 0.67⫾0.55, p⫽NS). Finally, LVAD support improved force-frequency relations of isolated superfused LV trabeculae (p⫽0.01) but not RV trabeculae. Conclusion: Reduction of hemodynamic load is a primary factor underlying several important features of reverse remodeling. These findings do not preclude a possible primary role of neurohormonal factors underlying other facets of reverse remodeling during LVAD support. Perspective: These findings provide valuable insights into the myocardial responses to mechanical ventricular unloading. The different hemodynamic characteristics of the right and left ventricle suggest a strong role for hemodynamic differences. The authors acknowledge other potential factors, but such factors are unlikely to yield a profound right-vs.-left ventricular differential effect. RC
Maron BJ, Niimura H, Casey SA, et al. J Am Coll Cardiol 2001; 38:315–21. Study Question: The authors evaluated whether left ventricular hypertrophy (LVH) can be demonstrated during adulthood in genetically affected relatives with hypertrophic cardiomyopathy (HCM). Hypertrophic cardiomyopathy is a heterogeneous cardiac disease caused by mutations in nine genes that encode proteins of the sarcomere. Mutations in cardiac myosin-binding protein C (MyBPC) gene have been associated with age-related penetrance. Methods and Results: As part of an evaluation of LVH in patients with HCM, the authors studied the phenotypic expression caused by MyBPC mutations in seven genotyped pedigrees. They utilized echocardiography and 12-lead electrocardiography. Of 119 family members studied, 61 were identified with a MyBPC mutation, including 21 genetically affected relatives (34%) who did not express the HCM morphologic phenotype (by virtue of showing normal left ventricular wall thickness). Of these 21 phenotype-negative individuals, nine were children, presumably in the prehypertrophic phase, and 12 were adults. Of the 12 adults with normal wall thickness ⱕ12 mm (seven also with normal electrocardiograms), five underwent serial evaluation, over 4 – 6 years. Three of these five adults developed LVH in mid life, appearing for the first time at 33, 34 and 42 years of age, respectively, not associated with outflow obstruction or significant symptoms. Conclusion: In adults with HCM, disease-causing MyBPC mutations are not uncommonly associated with absence of LVH on echocardiogram. Delayed remodeling with the development of LVH appearing de novo in adulthood, substantiates the principle of age-related penetrance for MyBPC mutations in HCM. These observations challenge prevailing perceptions regarding the HCM clinical spectrum and family screening strategies and further characterize the evolution of LVH in this disease. Perspective: Although a relatively small cohort, these are carefully conducted studies, and the conclusions of the authors are substantiated by their data. The observations provide further evidence that knowledge of the specific genetic mutations in cardiomyopathy will help determine the most effective screening strategy for families affected. RC
Plasma Nitric Oxide Level in Heart Failure Secondary to Left Ventricular Diastolic Dysfunction Yu CM, Fung PCW, Chan G, Lai HWH, Wang Q, Lau CP. Am J Cardiol 2001;88:867–70. Study Question: Nitric oxide (NO) is a free radical that is elevated in the plasma of patients with systolic heart failure.
ACC CURRENT JOURNAL REVIEW Jan/Feb 2002
51