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Progression to clinical heart failure—volume overload
ETIOLOGY,
PROGNOSIS
FOCUS: Heart Failure ETIOLOGY ACCEL Excerpt Revisitation Progression Overload
to Clinical
Heart
Failure-Volume
Robert D. Bonow, MD, Chicago, Illinois. Interviewed by Bruce H. Bmndage, MD. Originally in ACCEL No. 27, #3, March 1995. Updated October 1996.
Dr. Brundage: Dr. Bonow, we are interested in your experiences in the management of valve regurgitation relative to the progression to clinical heart failure. Dr. Bonow: A place that we might start is to address the importance of left ventricular function in the outcome of patients with aortic or mitral regurgitation, Much has been learned over the past two decades about the response of the left ventricle to valvular regurgitation and how the chamber dilates as an adaptive mechanism and hypertrophies to maintain systolic function in a normal range. But as the load excess continues and preload reserve is exhausted, left ventricular systolic function falls, ejection fraction falls and many patients develop symptoms at that point. At this early stage, the process may still be a reversible phenomenon, but if allowed to proceed too long irreversible left ventricular dysfunction ensues. Accordingly, the key to management is to identify those patients who are in the intermediate state where ventricular function is beginning to deteriorate due to loading abnormalities, but the dysfunction is still reversible, versus those patients who are progressing to irreversible dysfunction, The clinical challenge is to determine the optimal time to intervene and recommend valve replacement or repair. Dr. Btundage: What technique do you use to identify this intermediate state group of patients who have early signs of left ventricular dysfunction, perhaps subtle, but may not be symptomatic? Dr. Bonow: There are a number of techniques that we could discuss. Perhaps the most important is a careful history and physical examination, When a patient is developing angina or presyncope or moderate to severe exertional dyspnea, such patients do better both functionally and prognostically if interventions are done at that point in time. However, if you wait for symptoms to develop and use symptoms as the only indication for surgery, in some patients we have waited too long as irreversible left ventricular dysfunction can develop before symptoms develop. This is where the noninvasive techniques developed over the past two decades give us information of importance. Echocardiography can be used to assess left ventricular chamber size and systolic function, the degree of hypertrophy, assessment of the se-
AND
THERAPY
verity of the valvular regurgitation and information about valve anatomy. The important findings are the extent of left ventricular dilatation and whether or not systolic function is normal. Radionuclide angiography also may be used as a way of quantitating ventricular systolic function. Clinically, I use the echocardiogram serially to identify which patients are stable or which patients are progressing, developing more dilation and deterioration of systolic function; I use the radionuclide angiogram as a backup, independent measurement to validate the echocardiographic findings when those findings suggest it is time to consider intervening or when the echocardiographic data are equivocal. Dr. Brundage: What specifically do you look for on the radionuclide study? Just ejection fraction or do you look for other things? Dr. Borrow: Ejection fraction is the most important measurement. Most of the data relative to aortic regurgitation indicate that ejection fraction is an important risk predictor. This is ejection fraction at rest. The data with exercise are still somewhat difficult to interpret. I would not intervene in a patient solely because ejection fraction decreases with exercise. This appears to happen very early along the natural history spectrum. It is important to realize that in some patients you can allow the ejection fraction at rest to decrease below normal, as long as you intervene at that point in time. Those patients tend to do very well if intervention is prompt at that stage. Indices of ventricular volume also are quite important. In a laboratory that has wellvalidated volumetric measurements with radionuclide angiography, the quantitative volume information can be quite important. It is intriguing to think about the possibilities of some of the new imaging modalities that can give us much more accurate and quantitative measures of ventricular mass and volume such as magnetic resonance imaging or tine computed tomography. Dr. Brunduge: You have done some elegant work in assessing diastolic function using radioisotope techniques. Is there useful information to be derived from the evaluation of the volume overloaded patient? Dr. Bonow: There certainly are diastolic abnormalities that develop in relation to the development of left ventricular hypertrophy. These are very difficult to assess in patients with volume overload because of the adaptive changes the ventricle goes through to maintain filling pressures in the normal range despite a major increase in volume. That makes the measurements we use to assess diastolic function very problematic in volume overload, therefore I do not think they help clinically. I would like to emphasize the difference in physiology between aortic regurgitation and mitral regurgitation. The measures of systolic function and ventricular size work quite well for aortic regurgitation but
ETIOLOGY,
PROGNOSIS
in mitral regurgitation, because of the changes in load related to the regurgitant lesion itself, that is, the ventricle can eject into the low pressure left atrium, there is an afterload reducing effect, and measures of systolic “pump” function tend to overestimate true ventricular performance. With mitral regurgitation these measurements are very tricky and there is no good noninvasive measurement yet to serve as a threshold beyond which surgery should be recommended. Thus, the timing of surgery for mitral regurgitation is very difficult. The important thing is looking at the patient over a period of time and determining whether there is progression of ventricular size or deterioration of function. The difference between mitral and aortic regurgitation is that with mitral regurgitation one does not want the ejection fraction to decrease below normal or the end-systolic volume to increase substantially. Dr. Brunduge: Your threshold is lower for intervention in mitral regurgitation? Dr. Bonow: Yes, that is right. And, the newer surgical techniques have been very exciting with mitral valve repair compared to replacement. The postoperative function and survival outcome of patients is much better with repair, which raises the intriguing issue that one consider intervening even earlier in a patient if the patient is a candidate for mitral valve repair. In addition, preservation of the papillary muscles and chordal apparatus is very important in preserving ventricular function in those patients who undergo mitral valve replacement. In essence, we are rewriting the story of mitral regurgitation because of these new surgical techniques. (Ed.)
The Progression Heart Failure
From Hypertension
Effects of Aging on Neuroendocrine Activation in Subjects and Patients in the Presence and Absence of Heart Failure With Left Ventricular Systolic Dysfunction D.P. Dutka, I. Olivotto, 5. Ward, C.M. Oakley, M. Impailomeni, J.G.F. Cleland. MRC CRIHF, University of Glasgow, University Avenue, Glasgow, Great Britain. Am ] Cardiol 1996;77:1197-1201.
The neuroendocrine profile and echocardiographic features of 40 patients (81 2 1 years, mean f standard error) with heart failure and impaired left ventricular systolic function were compared with those of an age-matched group of healthy subjects, 20 younger patients with heart failure (aged 58 + 1 years), and 15 younger healthy subjects. Normal elderly subjectshad a neuroendocrine profile similar to that of healthy younger subjectsapart from elevated plasmanorepinephrine (958 t 84 vs 302 I+_118 pg/ml; p < 0.001) and atria1 natriuretic peptide (40 -+ 6 vs 28 -’ 5 pg/ml; p < 0.05). Despite a similar severity of heart failure, elderly patients had smaller ventricular dimensions (left ventricular internal dimension in diastole 5 1 + 2 vs 69 + 3 mm; p < 0.0001) and greater impairment of ventricular complianceusing Doppler indexes. Plasmanorepinephrine washigher (1,191 + 80 vs 620 -+ 67 pg/ml; p < O.Ol), and plasmaatria1natriuretic peptide, plasmaactive renin, and angiotensinII were lower in the elderly than tn the younger patients with heart failure. As functional capacity declines with age, elderly patients may have less severe cardiac dysfunction for any given level of functional impairment, and this may account for most of the differences in
D. Levy, M.G. Larson, R.S. Vasan, W.B. Rannel, R.R.L Ho. Framingham Heart Study, Framingham, MA. J Am tled Assoc 1996;275:1557-62.
Objectives: To study the relative and population-attributable risks of hypertension for the development of congestive heart failure (CHF), to assess the time course of progression from hypertension to CHF, and to identify risk factors that contribute to the development of overt heart failure in hypertensive subjects. Design: Inception cohort study. Setting: General community. Participants: Original Framingham Heart Study and Framingham Offspring Study participants aged 40 to 89 years and free of CHF. To reflect more contemporary experience, the starting point of this study was January 1, 1970. Exposure Measures: Hypertension (blood pressureof at least 140 mm Hg systolic or 90 mm Hg diastolic or current useof medicationsfor treatment of high blood pressure)and other potential CHF risk factors were assessed at periodic clinic examinations. OutcomeMeasure: The development of CHF. Results:A total of 5143 eligible subjects contributed 72,422 person-years of observation. CURRENT
JOURNAL
THERAPY
During up to 20.1 years of follow-up (mean, 14.1 years), there were 392 new casesof heart failure; in 91% (357/392), hypertension antedated the development of heart failure. Adjusting for age and heart failure risk factors in proportional hazardsregressionmodels,the hazard for developing heart failure in hypertensive compared with normotensive subjects was about 2-fold in men and 3-fold in women. Multivariable analysesrevealedthat hypertension had a high population-attributable risk for CHF, accounting for 39% of casesin men and 59% in women. Among hypertensive subjects,myocardial infarction, diabetes,left ventricular hypertrophy, and valvular heart diseasewere predictive of increasedrisk for CHF in both sexes.Survival following the onsetof hypertensive CHF wasbleak; only 24% of men and 31% of women survived 5 years. Conclusions: Hypertension was the most common risk factor for CHF, and it contributed a large proportion of heart failure casesin this population-based sample. Preventive strategies directed toward earlier and more aggressive blood pressure control are likely to offer the greatest. promise for reducing the incidence of CHF and its associatedmortality.
to Congestive
ACC
AND
REVIEW
37
March/April
1997
PROGNOSIS
FOCUS: Heart Failure ETIOLOGY ACCEL Excerpt Revisitation Progression Overload
to Clinical
Heart
Failure-Volume
Robert D. Bonow, MD, Chicago, Illinois. Interviewed by Bruce H. Bmndage, MD. Originally in ACCEL No. 27, #3, March 1995. Updated October 1996.
Dr. Brundage: Dr. Bonow, we are interested in your experiences in the management of valve regurgitation relative to the progression to clinical heart failure. Dr. Bonow: A place that we might start is to address the importance of left ventricular function in the outcome of patients with aortic or mitral regurgitation, Much has been learned over the past two decades about the response of the left ventricle to valvular regurgitation and how the chamber dilates as an adaptive mechanism and hypertrophies to maintain systolic function in a normal range. But as the load excess continues and preload reserve is exhausted, left ventricular systolic function falls, ejection fraction falls and many patients develop symptoms at that point. At this early stage, the process may still be a reversible phenomenon, but if allowed to proceed too long irreversible left ventricular dysfunction ensues. Accordingly, the key to management is to identify those patients who are in the intermediate state where ventricular function is beginning to deteriorate due to loading abnormalities, but the dysfunction is still reversible, versus those patients who are progressing to irreversible dysfunction, The clinical challenge is to determine the optimal time to intervene and recommend valve replacement or repair. Dr. Btundage: What technique do you use to identify this intermediate state group of patients who have early signs of left ventricular dysfunction, perhaps subtle, but may not be symptomatic? Dr. Bonow: There are a number of techniques that we could discuss. Perhaps the most important is a careful history and physical examination, When a patient is developing angina or presyncope or moderate to severe exertional dyspnea, such patients do better both functionally and prognostically if interventions are done at that point in time. However, if you wait for symptoms to develop and use symptoms as the only indication for surgery, in some patients we have waited too long as irreversible left ventricular dysfunction can develop before symptoms develop. This is where the noninvasive techniques developed over the past two decades give us information of importance. Echocardiography can be used to assess left ventricular chamber size and systolic function, the degree of hypertrophy, assessment of the se-
AND
THERAPY
verity of the valvular regurgitation and information about valve anatomy. The important findings are the extent of left ventricular dilatation and whether or not systolic function is normal. Radionuclide angiography also may be used as a way of quantitating ventricular systolic function. Clinically, I use the echocardiogram serially to identify which patients are stable or which patients are progressing, developing more dilation and deterioration of systolic function; I use the radionuclide angiogram as a backup, independent measurement to validate the echocardiographic findings when those findings suggest it is time to consider intervening or when the echocardiographic data are equivocal. Dr. Brundage: What specifically do you look for on the radionuclide study? Just ejection fraction or do you look for other things? Dr. Borrow: Ejection fraction is the most important measurement. Most of the data relative to aortic regurgitation indicate that ejection fraction is an important risk predictor. This is ejection fraction at rest. The data with exercise are still somewhat difficult to interpret. I would not intervene in a patient solely because ejection fraction decreases with exercise. This appears to happen very early along the natural history spectrum. It is important to realize that in some patients you can allow the ejection fraction at rest to decrease below normal, as long as you intervene at that point in time. Those patients tend to do very well if intervention is prompt at that stage. Indices of ventricular volume also are quite important. In a laboratory that has wellvalidated volumetric measurements with radionuclide angiography, the quantitative volume information can be quite important. It is intriguing to think about the possibilities of some of the new imaging modalities that can give us much more accurate and quantitative measures of ventricular mass and volume such as magnetic resonance imaging or tine computed tomography. Dr. Brunduge: You have done some elegant work in assessing diastolic function using radioisotope techniques. Is there useful information to be derived from the evaluation of the volume overloaded patient? Dr. Bonow: There certainly are diastolic abnormalities that develop in relation to the development of left ventricular hypertrophy. These are very difficult to assess in patients with volume overload because of the adaptive changes the ventricle goes through to maintain filling pressures in the normal range despite a major increase in volume. That makes the measurements we use to assess diastolic function very problematic in volume overload, therefore I do not think they help clinically. I would like to emphasize the difference in physiology between aortic regurgitation and mitral regurgitation. The measures of systolic function and ventricular size work quite well for aortic regurgitation but
ETIOLOGY,
PROGNOSIS
in mitral regurgitation, because of the changes in load related to the regurgitant lesion itself, that is, the ventricle can eject into the low pressure left atrium, there is an afterload reducing effect, and measures of systolic “pump” function tend to overestimate true ventricular performance. With mitral regurgitation these measurements are very tricky and there is no good noninvasive measurement yet to serve as a threshold beyond which surgery should be recommended. Thus, the timing of surgery for mitral regurgitation is very difficult. The important thing is looking at the patient over a period of time and determining whether there is progression of ventricular size or deterioration of function. The difference between mitral and aortic regurgitation is that with mitral regurgitation one does not want the ejection fraction to decrease below normal or the end-systolic volume to increase substantially. Dr. Brunduge: Your threshold is lower for intervention in mitral regurgitation? Dr. Bonow: Yes, that is right. And, the newer surgical techniques have been very exciting with mitral valve repair compared to replacement. The postoperative function and survival outcome of patients is much better with repair, which raises the intriguing issue that one consider intervening even earlier in a patient if the patient is a candidate for mitral valve repair. In addition, preservation of the papillary muscles and chordal apparatus is very important in preserving ventricular function in those patients who undergo mitral valve replacement. In essence, we are rewriting the story of mitral regurgitation because of these new surgical techniques. (Ed.)
The Progression Heart Failure
From Hypertension
Effects of Aging on Neuroendocrine Activation in Subjects and Patients in the Presence and Absence of Heart Failure With Left Ventricular Systolic Dysfunction D.P. Dutka, I. Olivotto, 5. Ward, C.M. Oakley, M. Impailomeni, J.G.F. Cleland. MRC CRIHF, University of Glasgow, University Avenue, Glasgow, Great Britain. Am ] Cardiol 1996;77:1197-1201.
The neuroendocrine profile and echocardiographic features of 40 patients (81 2 1 years, mean f standard error) with heart failure and impaired left ventricular systolic function were compared with those of an age-matched group of healthy subjects, 20 younger patients with heart failure (aged 58 + 1 years), and 15 younger healthy subjects. Normal elderly subjectshad a neuroendocrine profile similar to that of healthy younger subjectsapart from elevated plasmanorepinephrine (958 t 84 vs 302 I+_118 pg/ml; p < 0.001) and atria1 natriuretic peptide (40 -+ 6 vs 28 -’ 5 pg/ml; p < 0.05). Despite a similar severity of heart failure, elderly patients had smaller ventricular dimensions (left ventricular internal dimension in diastole 5 1 + 2 vs 69 + 3 mm; p < 0.0001) and greater impairment of ventricular complianceusing Doppler indexes. Plasmanorepinephrine washigher (1,191 + 80 vs 620 -+ 67 pg/ml; p < O.Ol), and plasmaatria1natriuretic peptide, plasmaactive renin, and angiotensinII were lower in the elderly than tn the younger patients with heart failure. As functional capacity declines with age, elderly patients may have less severe cardiac dysfunction for any given level of functional impairment, and this may account for most of the differences in
D. Levy, M.G. Larson, R.S. Vasan, W.B. Rannel, R.R.L Ho. Framingham Heart Study, Framingham, MA. J Am tled Assoc 1996;275:1557-62.
Objectives: To study the relative and population-attributable risks of hypertension for the development of congestive heart failure (CHF), to assess the time course of progression from hypertension to CHF, and to identify risk factors that contribute to the development of overt heart failure in hypertensive subjects. Design: Inception cohort study. Setting: General community. Participants: Original Framingham Heart Study and Framingham Offspring Study participants aged 40 to 89 years and free of CHF. To reflect more contemporary experience, the starting point of this study was January 1, 1970. Exposure Measures: Hypertension (blood pressureof at least 140 mm Hg systolic or 90 mm Hg diastolic or current useof medicationsfor treatment of high blood pressure)and other potential CHF risk factors were assessed at periodic clinic examinations. OutcomeMeasure: The development of CHF. Results:A total of 5143 eligible subjects contributed 72,422 person-years of observation. CURRENT
JOURNAL
THERAPY
During up to 20.1 years of follow-up (mean, 14.1 years), there were 392 new casesof heart failure; in 91% (357/392), hypertension antedated the development of heart failure. Adjusting for age and heart failure risk factors in proportional hazardsregressionmodels,the hazard for developing heart failure in hypertensive compared with normotensive subjects was about 2-fold in men and 3-fold in women. Multivariable analysesrevealedthat hypertension had a high population-attributable risk for CHF, accounting for 39% of casesin men and 59% in women. Among hypertensive subjects,myocardial infarction, diabetes,left ventricular hypertrophy, and valvular heart diseasewere predictive of increasedrisk for CHF in both sexes.Survival following the onsetof hypertensive CHF wasbleak; only 24% of men and 31% of women survived 5 years. Conclusions: Hypertension was the most common risk factor for CHF, and it contributed a large proportion of heart failure casesin this population-based sample. Preventive strategies directed toward earlier and more aggressive blood pressure control are likely to offer the greatest. promise for reducing the incidence of CHF and its associatedmortality.
to Congestive
ACC
AND
REVIEW
37
March/April
1997