- Email: [email protected]
Mitral Regurgitation and death while awaiting cardiac transplantation
11. Kupti M, Koskinen P, SuokasA, Ventill M. Left ventricular filling impairmerit in asymptomaticchronic alcoholics.Am J Cardiol 1990;66: 1473-1477. 12. ThomasJD, Weytnan AE EchocardiographicDoppler evaluation of left ventricular diastolic function. Physicsand physiology. Circulation 1991;84:977-990. 13. Kupti M. Diastolic heartfunction andfailure. J Intern Med 1991;229:47%481.
14. Nisbimura RA, Abel MD, Hatle LK, Tajik AJ. Assessmentof diastolic fonction of the heart:backgroundandcurrentapplicationsof Doppler echocardiography.
Mitral Regurgitation Transplantation Jamie B. Conti,
MD,
Part II. Clinical studies.Mayo Clin Proc 1989;64:181-204. 15. Ochi H, SbimadaT, lkuma I, Morioka S, Moriyama K. Effect of a decrease in aortic complianceon the isovolumic relaxation period of the left ventricle io man. Am J Noninvas Cardiol 1991;5:149-154. 16. Hart MV, HosenpudJD, Hobimer RA, Morton MJ. Hemodynamicsdur@: pregnancy and sex steroid administration in guinea pigs. Am J Physiol
1985;249:R179-R185.
and Death While Awaiting
and Roger M. Mills, Jr.,
Cardiac
MD
atients selected as candidatesfor orthotopic cardiac study period, survived >3 months and had a successfil transplant (late transplant). The 3-month period was ar-, poor prognosis. Most cardiac transplantation centers re- bitrarily chosenas the cutofffor early versus late death, quire patients to have an estimated annual mortality of given an average wait for transplantation of 2.3 months, 50% as a criterion for selection as a potential recipient. death within 3 months identij?esa group of patients un-, Even in this highly selected population, there is likely to survive until transplantation. All paiients were receiving stable doses of vasodila-, considerablevariation in prognosis. Some patients tolerate months of medical therapy while awaiting tors and diuretics at the time of evaluation. Ejection transplantation, whereas others die, often unpredictably. fraction was computed using the Bullet (hemispherelcylFrom 1987 to 1990, the average patient waiting period inder) formula. Mitral regurgitation was assessedas from selection as a candidate to transplantation at the grades I through IV using the criteria outlined by HelmUniversity of Florida was 2.3 months. Of 137 patients eke et al.] All echocardiograms were obtained using either a listed with the United Network for Organ Sharing during this period, 19 (14%) died while awaiting transplan- Hewlett-Packard Sonos 500 (Hewlett-Packard Corpotation. We performed a retrospective evaluation of these ration, Andover, Massachusetts) or an ATL Ultramark patients to test the hypothesis that echocardiographicev- 6 (Advanced Technologies Lab, Botell, Washington). idence of severe mitral regurgitation may be a simple, Colorjlow imaging was obtained using standard transeasily obtained marker for early death while awaiting ducers ranging between 2.0 and 3.5 MHz. Characteristics of the 3 groups are listed in Table I. transplantation. From all University of Florida patients registered There were no sign@cant differences among the 3 between January 1987 and December 1991 as candi- groups in sex distribution, ejection fiaction or antiardatesfor cardiac transplantation, we identljied 19 who rhythmic therapy. Early patients were significantly died awaiting transplantation. Of these 19 patients, 18 younger than either late or late transplant patients. Of had technically satisfactory 2-dimensional and Doppler 10 early patients, 8 had grade III or IV mitral regurgitransthoracic echocardiograms during their evaluation tation; in contrast, 7 of 8 late and all 5 late transplant for transplantation. These 18 patients were divided into patients had grade I or II mitral regurgitation 2 groups: the first included 10 patients who died ~3 (p = 0.003). The data suggestthat echocardiographic demonstramonths after selection as a candidate (early), and the second group included 8 patients who died 23 months tion of s&r&ant (grade III or IV) mitral regurgitation after selection (late). Additional data were obtained in in patients receiving oral vasodilator therapy predicts 5 patients who were selected as candidates during the early death while awaiting transplantation. Death while awaiting cardiac transplantation remains a poorly understood phenomenon.All patients selectedfor transplanta-
P transplantation have end-stageheart diseasewith a
From the Department of Medicine, Division of Cardiology, University of Florida College of Medicine, P.0. Box 100277, JHMHC Gainesville, Florida 32610-0277. Manuscript received May 18, 1992; revised manuscript received and accepted August 31,1992. TABLE
I Characteristics
No. of pts. Age (year) Men/women Ejection fraction Antiarrhythmic therapy Grade Ill-IV mitral regurgitation
1: Negative Feedback Loop Volume Load 2” MR
of Patients Studied Early
Late
Death
Death
10
8
40*19 614 19 f 4 8 8
55*7 810
19 f 4 2 1
Late Transplant 5 57 ” 8 5/o 20 i- 9 2 0
p Value 0.04* 0.06t
0.89t
*p value results from I-way analysis of variance, followed by Duncan’s multiple rangetest to identify group differences. tp value results from extension of Fisher’s exact test for contingency tables larger than 2 x 2.
Dilation
Worse MR
0.09t 0.003t
Figure 1 ._ -
__
FIGURE 1. Progressive volume loading regurgitation (MR). Negative feedback
and worsening loop.
_
m hal
BRIEF REPORTS 617
tion have severecardiovasculardisease,and to date there is no simple, reliable marker for identifying those whose heart failure appearsreasonably well-compensated,but who are at high risk for early death. Parameshwaret al2 recently developed a multivariate analysis that found plasma sodium concentration, left ventricular ejection fraction and peak oxygen consumption to be predictive of outcome in 127 patients with severe chronic heart failure. However, ejection fraction and oxygen consumption are so reduced in the pretransplant population that these measuresmay no longer be useful, and the multivariate model is difficult to use clinically. Our tindings are consistent with the observation that patients with end-stagecoronary diseaseand mitral regurgitation benefit more from transplantation than aneurysm resection.3 Lehman et al4 have also demonstratedthe association of severemitral regurgitation and subsequentearly mortality in 206 patients studied within 7 hours of myocardial infarction. One-year mortality in this group was 5% in patients without mitral regurgitation, 18% with mild and 60% with moderate to severe regurgitation, and this mortality distribution was evident as early as 10 days. The mechanismsresponsible for this dire prognosis are not clear. The tendency for functional mitral regurgitation to worsen in a negative feedback loop becauseof progressive volume loading may be 1 factor involved (Pigure 1). Another hypothesis is that mitral regurgitation is a marker for connective tissue destruction and
616
THE AMERICANJOURNALOF CARDIOLOGY VOLUME71
loss of interstitial support structures.In chronic congestive heart failure, remodeling occurs in both the myocytes and connective tissue matrix of the heart. Recent reports suggest that cellular remodeling is reversible if the initiating stressis removed, but that matrix or interstitial remodeling may be irreversible.5JjLoss of collagen matrix may be the pathophysiology underlying cardiac dilatation, altered compliance and subsequentheart failure. Thus, refractory severemitral regurgitation may indicate a terrninal situation. The number of patients who can be studied at any 1 transplant center is limited. Despite small numbers of patients, however, the data are highly suggestive that echocardiographicevidence of moderateto severemitral regurgitation persisting with adequate oral vasodilator therapy is a predictor of early death while awaiting heart transplantation. REFERENCES 1. Helmcke F, Nanda NC, Hsiung MC, Sot0 B, Adey CK, Goyal RG, Gatewood RP, Jr. Color Doppler assessment of mitml regurgitation with orthogonal planes. Circulation 1987;75:175-183. 2. Parameshwar J, Keegan J, Spanow J, Sutton GC, Poole-Wilson PA. Predictors of prognosis in severe chronic heart failure. Am He&J 1992;123:421-426. 3. Mangschau A, G&ran 0, Forfang K, Simonsen S, Froysaker T. Left venhicular aneurysm and severe cardiac dysfunction: heart transplantation or aneurysm surgery? J Heart Transplant 1989;8:486-493. 4. Lehman KG, Francis CK, Dodge JIT, and the TIMI Study Group. Mitral regurgitation in early myccardial infarction; incidence, clinical detection, and prognostic implications. Am Znrern Med 1992;117:10-17. 5. Caullield JB, Wokowicz PE. A mechanism for cardiac dilatation. Heart Failure 1990;6:13&150. 6. Eng C. Enlargement of the heart. Heart Failure 1991;7:15-24.
MARCH1, 1993
14. Nisbimura RA, Abel MD, Hatle LK, Tajik AJ. Assessmentof diastolic fonction of the heart:backgroundandcurrentapplicationsof Doppler echocardiography.
Mitral Regurgitation Transplantation Jamie B. Conti,
MD,
Part II. Clinical studies.Mayo Clin Proc 1989;64:181-204. 15. Ochi H, SbimadaT, lkuma I, Morioka S, Moriyama K. Effect of a decrease in aortic complianceon the isovolumic relaxation period of the left ventricle io man. Am J Noninvas Cardiol 1991;5:149-154. 16. Hart MV, HosenpudJD, Hobimer RA, Morton MJ. Hemodynamicsdur@: pregnancy and sex steroid administration in guinea pigs. Am J Physiol
1985;249:R179-R185.
and Death While Awaiting
and Roger M. Mills, Jr.,
Cardiac
MD
atients selected as candidatesfor orthotopic cardiac study period, survived >3 months and had a successfil transplant (late transplant). The 3-month period was ar-, poor prognosis. Most cardiac transplantation centers re- bitrarily chosenas the cutofffor early versus late death, quire patients to have an estimated annual mortality of given an average wait for transplantation of 2.3 months, 50% as a criterion for selection as a potential recipient. death within 3 months identij?esa group of patients un-, Even in this highly selected population, there is likely to survive until transplantation. All paiients were receiving stable doses of vasodila-, considerablevariation in prognosis. Some patients tolerate months of medical therapy while awaiting tors and diuretics at the time of evaluation. Ejection transplantation, whereas others die, often unpredictably. fraction was computed using the Bullet (hemispherelcylFrom 1987 to 1990, the average patient waiting period inder) formula. Mitral regurgitation was assessedas from selection as a candidate to transplantation at the grades I through IV using the criteria outlined by HelmUniversity of Florida was 2.3 months. Of 137 patients eke et al.] All echocardiograms were obtained using either a listed with the United Network for Organ Sharing during this period, 19 (14%) died while awaiting transplan- Hewlett-Packard Sonos 500 (Hewlett-Packard Corpotation. We performed a retrospective evaluation of these ration, Andover, Massachusetts) or an ATL Ultramark patients to test the hypothesis that echocardiographicev- 6 (Advanced Technologies Lab, Botell, Washington). idence of severe mitral regurgitation may be a simple, Colorjlow imaging was obtained using standard transeasily obtained marker for early death while awaiting ducers ranging between 2.0 and 3.5 MHz. Characteristics of the 3 groups are listed in Table I. transplantation. From all University of Florida patients registered There were no sign@cant differences among the 3 between January 1987 and December 1991 as candi- groups in sex distribution, ejection fiaction or antiardatesfor cardiac transplantation, we identljied 19 who rhythmic therapy. Early patients were significantly died awaiting transplantation. Of these 19 patients, 18 younger than either late or late transplant patients. Of had technically satisfactory 2-dimensional and Doppler 10 early patients, 8 had grade III or IV mitral regurgitransthoracic echocardiograms during their evaluation tation; in contrast, 7 of 8 late and all 5 late transplant for transplantation. These 18 patients were divided into patients had grade I or II mitral regurgitation 2 groups: the first included 10 patients who died ~3 (p = 0.003). The data suggestthat echocardiographic demonstramonths after selection as a candidate (early), and the second group included 8 patients who died 23 months tion of s&r&ant (grade III or IV) mitral regurgitation after selection (late). Additional data were obtained in in patients receiving oral vasodilator therapy predicts 5 patients who were selected as candidates during the early death while awaiting transplantation. Death while awaiting cardiac transplantation remains a poorly understood phenomenon.All patients selectedfor transplanta-
P transplantation have end-stageheart diseasewith a
From the Department of Medicine, Division of Cardiology, University of Florida College of Medicine, P.0. Box 100277, JHMHC Gainesville, Florida 32610-0277. Manuscript received May 18, 1992; revised manuscript received and accepted August 31,1992. TABLE
I Characteristics
No. of pts. Age (year) Men/women Ejection fraction Antiarrhythmic therapy Grade Ill-IV mitral regurgitation
1: Negative Feedback Loop Volume Load 2” MR
of Patients Studied Early
Late
Death
Death
10
8
40*19 614 19 f 4 8 8
55*7 810
19 f 4 2 1
Late Transplant 5 57 ” 8 5/o 20 i- 9 2 0
p Value 0.04* 0.06t
0.89t
*p value results from I-way analysis of variance, followed by Duncan’s multiple rangetest to identify group differences. tp value results from extension of Fisher’s exact test for contingency tables larger than 2 x 2.
Dilation
Worse MR
0.09t 0.003t
Figure 1 ._ -
__
FIGURE 1. Progressive volume loading regurgitation (MR). Negative feedback
and worsening loop.
_
m hal
BRIEF REPORTS 617
tion have severecardiovasculardisease,and to date there is no simple, reliable marker for identifying those whose heart failure appearsreasonably well-compensated,but who are at high risk for early death. Parameshwaret al2 recently developed a multivariate analysis that found plasma sodium concentration, left ventricular ejection fraction and peak oxygen consumption to be predictive of outcome in 127 patients with severe chronic heart failure. However, ejection fraction and oxygen consumption are so reduced in the pretransplant population that these measuresmay no longer be useful, and the multivariate model is difficult to use clinically. Our tindings are consistent with the observation that patients with end-stagecoronary diseaseand mitral regurgitation benefit more from transplantation than aneurysm resection.3 Lehman et al4 have also demonstratedthe association of severemitral regurgitation and subsequentearly mortality in 206 patients studied within 7 hours of myocardial infarction. One-year mortality in this group was 5% in patients without mitral regurgitation, 18% with mild and 60% with moderate to severe regurgitation, and this mortality distribution was evident as early as 10 days. The mechanismsresponsible for this dire prognosis are not clear. The tendency for functional mitral regurgitation to worsen in a negative feedback loop becauseof progressive volume loading may be 1 factor involved (Pigure 1). Another hypothesis is that mitral regurgitation is a marker for connective tissue destruction and
616
THE AMERICANJOURNALOF CARDIOLOGY VOLUME71
loss of interstitial support structures.In chronic congestive heart failure, remodeling occurs in both the myocytes and connective tissue matrix of the heart. Recent reports suggest that cellular remodeling is reversible if the initiating stressis removed, but that matrix or interstitial remodeling may be irreversible.5JjLoss of collagen matrix may be the pathophysiology underlying cardiac dilatation, altered compliance and subsequentheart failure. Thus, refractory severemitral regurgitation may indicate a terrninal situation. The number of patients who can be studied at any 1 transplant center is limited. Despite small numbers of patients, however, the data are highly suggestive that echocardiographicevidence of moderateto severemitral regurgitation persisting with adequate oral vasodilator therapy is a predictor of early death while awaiting heart transplantation. REFERENCES 1. Helmcke F, Nanda NC, Hsiung MC, Sot0 B, Adey CK, Goyal RG, Gatewood RP, Jr. Color Doppler assessment of mitml regurgitation with orthogonal planes. Circulation 1987;75:175-183. 2. Parameshwar J, Keegan J, Spanow J, Sutton GC, Poole-Wilson PA. Predictors of prognosis in severe chronic heart failure. Am He&J 1992;123:421-426. 3. Mangschau A, G&ran 0, Forfang K, Simonsen S, Froysaker T. Left venhicular aneurysm and severe cardiac dysfunction: heart transplantation or aneurysm surgery? J Heart Transplant 1989;8:486-493. 4. Lehman KG, Francis CK, Dodge JIT, and the TIMI Study Group. Mitral regurgitation in early myccardial infarction; incidence, clinical detection, and prognostic implications. Am Znrern Med 1992;117:10-17. 5. Caullield JB, Wokowicz PE. A mechanism for cardiac dilatation. Heart Failure 1990;6:13&150. 6. Eng C. Enlargement of the heart. Heart Failure 1991;7:15-24.
MARCH1, 1993