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Cardiac evaluation for simultaneous pancreas-kidney transplantation and incidence of cardiac perioperative complications: preliminary study
Cardiac Evaluation for Simultaneous Pancreas-Kidney Transplantation and Incidence of Cardiac Perioperative Complications: Preliminary Study N. Fossati, L. Meacci, G. Amorese, G. Bellissima, M. Pieri, S. Nardi, M. Esposito Vangone, L. Rondinini, R. Mariotti, A.S. Petronio, U. Boggi, G. Rizzo, P. Marchetti, A. Sansevero, and F. Mosca ABSTRACT Type I diabetes mellitus (IDDM) is associated with an increased cardiovascular risk, and eligibility protocols for simultaneous pancreas-kidney transplantation (SPKT) are consequently accurate for preoperative cardiovascular assessment. According to our algorithm, coronary angiography in SPKT candidates is indicated for patients not only experiencing previous cardiac events or symptoms, but also those with long-standing diabetes (more than 25 years) and/or age over 45 years. Furthermore, a basal transthoracic echocardiographic exam (TTE) is performed to assess cardiac volumes, left ventricular mass, systolic function, and kinesis. The aims of this study were to evaluate perioperative cardiac morbidity and mortality in 18 SPKT-eligible patients, divided into two groups on the basis of the presence/absence of angiographically evident coronary artery disease (CAD), as well as to assess the impact of left ventricular hypertrophy (LVH) on cardiac complications. Cardiac intraoperative morbidity and mortality and postoperative mortality and major morbidity were absent; minor cardiac morbidity consisted only of silent ischemic ECG alterations, without significant differences between groups, although the incidence seemed to be higher in the CAD-positive population. LVH detected preoperatively by TTE exam also failed to correlate with the incidence of such complications. Selection of SPKT candidates by coronary angiography may have positive effects on perioperative cardiac morbidity and mortality. A larger sample size is needed to give the study statistical power. Medium- and long-term follow-up studies are warranted to evaluate the effects of preoperative selection on survival rates.
A
N INCREASED CARDIOVASCULAR risk is commonly associated with type I diabetes mellitus (IDDM).1–3 Accordingly, eligibility protocols for simultaneous pancreas-kidney transplantation (SPKT) focus on the preoperative cardiovascular assessment to select patients who might maximally benefit from transplantation.4 However, invasive tests to evaluate the presence and extension of coronary artery disease (CAD) are not routinely recommended, and protocols may differ significantly. Typical indications for preoperative coronary angiography are cardiac events in the previous history or signs and/or symptoms of ischemic heart disease (IHD). In an attempt to improve selection of SPKT candidates, we decided to extend the indications for coronary angiography to patients with long-standing diabetes (more than 25 years) and/or over 45 years of age. Nonetheless, factors other than 0041-1345/04/$–see front matter doi:10.1016/j.transproceed.2004.02.036 582
coronary artery stenosis may account for perioperative cardiac complications in diabetic patients. More specifically, left ventricular hypertrophy (LVH) is a common finding among SPKT candidates, possibly representing ad-
From the I U.O. Anestesia e Rianimazione (N.F., L.M., G.A., G.B., M.P., S.N., M.E.V., A.S.), U.O. Nefrologia con Trapianti (G.R.), Azienda Ospedaliera Universitaria Pisana; Dipartimento Cardiotoracico (L.R., R.M., A.S.P.) and Dipartimento di Oncologia (U.B., F.M.), dei Trapiani e delle Nuove Tecnologie in Medicina; and Dipartimento di Endocrinologia e Metabolismo (P.M.), Universita` degli Studi di Pisa, Pisa, Italy. Address reprint requests to Dr Nicoletta Fossati, I U.O. Anestesia e Rianimazione, Azienda Ospedaliera Universitaria Pisana, Presidio Ospedaliero di Cisanello, Via Paradisa, 2, 56124 Pisa, Italy. E-mail: [email protected] © 2004 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 36, 582–585 (2004)
CARDIAC PERIOPERATIVE COMPLICATIONS
583
Table 1. Demographic Data and Severity of Disease Parameters
Table 2. Intra- and Postoperative Differences Between Groups
Parameter
CAD-negative
CAD-positive
t test
Age in years M/F Years of diabetes Dialysis (yes/no) Months of dialysis Arterial hypertension (yes/no) Autonomic neuropathy (yes/no) LVEF (%) LVMI (g/m2)
43.4 5/9 26.1 6/3 29 9/0 7/2 56.1 115.9
43.7 5/9 28.4 5/4 23.4 9/0 6/3 53.1 107.2
NS NS NS NS NS NS NS NS NS
All data are expressed as mean, unless otherwise specified.
junctive risk factor for cardiac events during and after surgery.5–7 The aims of this study were to evaluate the perioperative cardiac morbidity and mortality in 18 SPKT patients, divided into two groups on the basis of negative versus positive coronary artery angiograms, and to assess the relationship between LVH and the incidence of perioperative cardiac complications. PATIENTS AND METHODS Eighteen patients who underwent SPKT between February 2000 and May 2003 were retrospectively included in this study. All subjects underwent coronary angiography during the eligibility evaluation. They were divided into two homogeneous groups (CAD-positive and CAD-negative patients, see Table 1 for details). Two CAD-positive patients underwent coronary angioplasty (PTCA) before being enrolled in the transplant program. All patients had also been studied by the same operator with a routine transthoracic echocardiographic exam (TTE) to assess cardiac volumes, LV systolic function with determination of the ejection
Parameter
CAD-negative
CAD-positive
t test
Mean duration of surgery (hours) Intraoperative nitrates (%) Postoperative nitrates (%) ICU extubation (%) Postoperative dialysis (yes/no) Mean ICU stay Postop ischemic ECG signs
10.2 33 33 22 1/9 4.3 1/9
9.2 88 66 22 1/9 5.1 3/9
NS P ⬍ .05 P ⬍ .05 NS NS NS NS
fraction (EF%), LV mass index (MI), and kinesis. The perioperative period was considered to begin the day of surgery and to end on the 20th postoperative day. Data were analyzed using Student t test for differences between groups and chi-square analysis for the incidence of cardiac events. A P ⬍ .05 was considered statistically significant.
RESULTS
All patients are currently alive, with functioning grafts. No significant differences were found in their demographic data, severity of disease, and preoperative TTE parameters between the groups (Table 1). The anesthetic protocol and the intraoperative monitoring were the same for all patients. No significant differences were observed in the duration of surgery, rate of immediate extubation after surgery, recourse to postoperative dialysis, and length of ICU stay, while use of nitrate infusions was significantly more frequent among the CAD-positive group (P ⬍ .05, Table 2). Intraoperative cardiac morbidity and mortality, as well as postoperative mortality, were absent. Cardiac morbidity consisted only of silent ischemic ECG alterations in the early postoperative period during the ICU stay, their inci-
100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0%
CAD-positive
1
CAD -negative
Fig 1. Coronary artery stenosis and incidence of postoperative ischemic ECG signs. On the ordinate axis, percentages of patients with postoperative ECG alterations are represented.
584
FOSSATI, MEACCI, AMORESE ET AL
100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0%
no LVH on TTE
LVH on TTE
noLVHon ECG
LVH on ECG
Fig 2. TTE or ECG signs of LVH and incidence of ischemic ECG signs. On the ordinate axis, percentages of patients with postoperative ischemic ECG alterations are represented.
dence was not significantly different between groups, although more frequent among CAD-positive patients (3/9 vs 1/9, P ⫽ NS, Fig 1). Surprisingly, LVMI did not correlate with the incidence of such complications, while ECG signs of LVH showed a positive correlation with the occurrence of ischemic derangements (Fig 2). DISCUSSION
Perioperative cardiac morbidity and mortality represent major concerns when dealing with SPKT patients. Preoperative evaluation seeks to select candidates with an acceptable cardiac risk.8 Silent IHD is typical of IDDM, thus limiting the role of previous history, signs, and symptoms as eligibility criteria for coronary artery studies. Our current evaluation algorithm was designed by the cardiology team taking into account adjunctive risk factors, such as age, years of diabetes, smoking, family history of IHD, circulating lipid levels, and so on, to define a cumulative cardiac risk even in the absence of previous cardiac signs and/or symptoms. Cardiac mortality and major cardiac morbidity were absent in both cohorts of SPKT patients in the perioperative period, possibly suggesting a positive role of coronary angiography in preoperative selection, especially of CADpositive patients. However, the incidence (not statistically significant) of silent ECG alterations was higher among the CAD-positive group. Silent ischemic ECG signs occurred also in one patient of the CAD-negative group. Undoubtedly, coronary artery stenosis does not explain every aspect of cardiac dysfunction in diabetic patients.9,10 Diabetic vasculopathy typically affects the microcirculation, and coronary angiography may lack sensitivity to image distal branches of the coronary tree. Moreover, LVH has a high prevalence among our SPKT candidates, representing per se a harbinger of cardiovascular problems.5 In this setting, the negative effects of
small-vessel disease, enhanced by the presence of LVH, may have been responsible for ischemic ECG signs even with a CAD-negative angiographic study. The finding of an inverse relationship between LVH on TTE and the incidence of cardiac events was dismaying, being completely at variance with results in previous publications.5–7 While ECG signs of LVH seemed to correlate positively with the incidence of ischemic ECG alterations, none of these findings reached statistical significance. In addition, TTE and ECG detection of LVH poorly correlate and may actually be indicators of different aspects of the phenomenon.11,12 The lack of statistical significance of all results, and the paradoxical finding regarding LVH correlation with cardiac events, may be attributed to the small sample size. Larger series are needed to increase the power of the study. Medium- and long-term follow-up studies are also warranted to evaluate the real benefits of preoperative selection and successful SPKT on patient survival rates.
CONCLUSION
Preoperative evaluation with coronary angiography has possibly played a role in the absence of cardiac mortality and the low, relatively minor cardiac morbidity observed in our series in the perioperative period after SPKT. Although not statistically significant, the incidence of ischemic ECG appearances seems to correlate with the presence of CAD on preoperative angiograms, while LVH detected by TTE failed to show such a correlation. Our results may have been negatively affected by the small size of the sample, thus warranting further investigations to validate these observations. Finally, medium- and long-term follow-up studies are needed to evaluate the effects of preoperative selection on long-term posttransplant cardiac events and survival rates.
CARDIAC PERIOPERATIVE COMPLICATIONS
REFERENCES 1. Kannel WB, McGee DL: Diabetes and cardiovascular disease. The Framingham study. JAMA 241:2035, 1979 2. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus: Report of the Expert Committee on the diagnosis and classification of Diabetes Mellitus. Diabetes Care 20: 1183, 1997 3. Moss SE, Klein R, Klein BEK, et al: The association of glycemia and cause-specific mortality in a diabetic population. Arch Intern Med 154:2473, 1994 4. Stratta RJ, Taylor RJ, Gill IS: Pancreas transplantation: a managed cure approach to diabetes. Current Problems in Surgery 33:713, 1996 5. Messerli FH, Devereux RB: Left ventricular hypertrophy— good or evil? Am J Med 75:1, 1983 6. Kannel WB: Left ventricular hypertrophy as a risk factor in arterial hypertension. Eur Heart J 13(Suppl D):82, 1992
585 7. Bikkina M, Larson MG, Levy D: Asymptomatic ventricular arrhythmias and mortality risk in subjects with left ventricular hypertrophy. J Am Coll Cardiol 22:1111, 1993 8. Schweitzer EJ, Anderson L, Kuo PC: Safe pancreas transplantation in patients with coronary artery disease. Transplantation 63:1294, 1997 9. Nicolino A, Longobardi G, Furgi G: Left ventricular diastolic filling in diabetes mellitus with and without hypertension. Am J Hypertens 8:382, 1995 10. Illan F, Valdes-Chiavarri M, Tebar J: Anatomical and functional cardiac abnormalities in type 1 diabetes. Clin Investig 70:403, 1992 11. Kannel WB, Dannenberg AL, Levy D: Population implications of ECG left ventricular hypertrophy. Am J Cardiol 60:851, 1987 12. Levy D, Anderson KM, Savage DD, et al: Echocardiographically detected left ventricular hypertrophy, prevalence and risk factors. The Framingham Heart Study. Ann Intern Med 108:2, 1988
A
N INCREASED CARDIOVASCULAR risk is commonly associated with type I diabetes mellitus (IDDM).1–3 Accordingly, eligibility protocols for simultaneous pancreas-kidney transplantation (SPKT) focus on the preoperative cardiovascular assessment to select patients who might maximally benefit from transplantation.4 However, invasive tests to evaluate the presence and extension of coronary artery disease (CAD) are not routinely recommended, and protocols may differ significantly. Typical indications for preoperative coronary angiography are cardiac events in the previous history or signs and/or symptoms of ischemic heart disease (IHD). In an attempt to improve selection of SPKT candidates, we decided to extend the indications for coronary angiography to patients with long-standing diabetes (more than 25 years) and/or over 45 years of age. Nonetheless, factors other than 0041-1345/04/$–see front matter doi:10.1016/j.transproceed.2004.02.036 582
coronary artery stenosis may account for perioperative cardiac complications in diabetic patients. More specifically, left ventricular hypertrophy (LVH) is a common finding among SPKT candidates, possibly representing ad-
From the I U.O. Anestesia e Rianimazione (N.F., L.M., G.A., G.B., M.P., S.N., M.E.V., A.S.), U.O. Nefrologia con Trapianti (G.R.), Azienda Ospedaliera Universitaria Pisana; Dipartimento Cardiotoracico (L.R., R.M., A.S.P.) and Dipartimento di Oncologia (U.B., F.M.), dei Trapiani e delle Nuove Tecnologie in Medicina; and Dipartimento di Endocrinologia e Metabolismo (P.M.), Universita` degli Studi di Pisa, Pisa, Italy. Address reprint requests to Dr Nicoletta Fossati, I U.O. Anestesia e Rianimazione, Azienda Ospedaliera Universitaria Pisana, Presidio Ospedaliero di Cisanello, Via Paradisa, 2, 56124 Pisa, Italy. E-mail: [email protected] © 2004 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 36, 582–585 (2004)
CARDIAC PERIOPERATIVE COMPLICATIONS
583
Table 1. Demographic Data and Severity of Disease Parameters
Table 2. Intra- and Postoperative Differences Between Groups
Parameter
CAD-negative
CAD-positive
t test
Age in years M/F Years of diabetes Dialysis (yes/no) Months of dialysis Arterial hypertension (yes/no) Autonomic neuropathy (yes/no) LVEF (%) LVMI (g/m2)
43.4 5/9 26.1 6/3 29 9/0 7/2 56.1 115.9
43.7 5/9 28.4 5/4 23.4 9/0 6/3 53.1 107.2
NS NS NS NS NS NS NS NS NS
All data are expressed as mean, unless otherwise specified.
junctive risk factor for cardiac events during and after surgery.5–7 The aims of this study were to evaluate the perioperative cardiac morbidity and mortality in 18 SPKT patients, divided into two groups on the basis of negative versus positive coronary artery angiograms, and to assess the relationship between LVH and the incidence of perioperative cardiac complications. PATIENTS AND METHODS Eighteen patients who underwent SPKT between February 2000 and May 2003 were retrospectively included in this study. All subjects underwent coronary angiography during the eligibility evaluation. They were divided into two homogeneous groups (CAD-positive and CAD-negative patients, see Table 1 for details). Two CAD-positive patients underwent coronary angioplasty (PTCA) before being enrolled in the transplant program. All patients had also been studied by the same operator with a routine transthoracic echocardiographic exam (TTE) to assess cardiac volumes, LV systolic function with determination of the ejection
Parameter
CAD-negative
CAD-positive
t test
Mean duration of surgery (hours) Intraoperative nitrates (%) Postoperative nitrates (%) ICU extubation (%) Postoperative dialysis (yes/no) Mean ICU stay Postop ischemic ECG signs
10.2 33 33 22 1/9 4.3 1/9
9.2 88 66 22 1/9 5.1 3/9
NS P ⬍ .05 P ⬍ .05 NS NS NS NS
fraction (EF%), LV mass index (MI), and kinesis. The perioperative period was considered to begin the day of surgery and to end on the 20th postoperative day. Data were analyzed using Student t test for differences between groups and chi-square analysis for the incidence of cardiac events. A P ⬍ .05 was considered statistically significant.
RESULTS
All patients are currently alive, with functioning grafts. No significant differences were found in their demographic data, severity of disease, and preoperative TTE parameters between the groups (Table 1). The anesthetic protocol and the intraoperative monitoring were the same for all patients. No significant differences were observed in the duration of surgery, rate of immediate extubation after surgery, recourse to postoperative dialysis, and length of ICU stay, while use of nitrate infusions was significantly more frequent among the CAD-positive group (P ⬍ .05, Table 2). Intraoperative cardiac morbidity and mortality, as well as postoperative mortality, were absent. Cardiac morbidity consisted only of silent ischemic ECG alterations in the early postoperative period during the ICU stay, their inci-
100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0%
CAD-positive
1
CAD -negative
Fig 1. Coronary artery stenosis and incidence of postoperative ischemic ECG signs. On the ordinate axis, percentages of patients with postoperative ECG alterations are represented.
584
FOSSATI, MEACCI, AMORESE ET AL
100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0%
no LVH on TTE
LVH on TTE
noLVHon ECG
LVH on ECG
Fig 2. TTE or ECG signs of LVH and incidence of ischemic ECG signs. On the ordinate axis, percentages of patients with postoperative ischemic ECG alterations are represented.
dence was not significantly different between groups, although more frequent among CAD-positive patients (3/9 vs 1/9, P ⫽ NS, Fig 1). Surprisingly, LVMI did not correlate with the incidence of such complications, while ECG signs of LVH showed a positive correlation with the occurrence of ischemic derangements (Fig 2). DISCUSSION
Perioperative cardiac morbidity and mortality represent major concerns when dealing with SPKT patients. Preoperative evaluation seeks to select candidates with an acceptable cardiac risk.8 Silent IHD is typical of IDDM, thus limiting the role of previous history, signs, and symptoms as eligibility criteria for coronary artery studies. Our current evaluation algorithm was designed by the cardiology team taking into account adjunctive risk factors, such as age, years of diabetes, smoking, family history of IHD, circulating lipid levels, and so on, to define a cumulative cardiac risk even in the absence of previous cardiac signs and/or symptoms. Cardiac mortality and major cardiac morbidity were absent in both cohorts of SPKT patients in the perioperative period, possibly suggesting a positive role of coronary angiography in preoperative selection, especially of CADpositive patients. However, the incidence (not statistically significant) of silent ECG alterations was higher among the CAD-positive group. Silent ischemic ECG signs occurred also in one patient of the CAD-negative group. Undoubtedly, coronary artery stenosis does not explain every aspect of cardiac dysfunction in diabetic patients.9,10 Diabetic vasculopathy typically affects the microcirculation, and coronary angiography may lack sensitivity to image distal branches of the coronary tree. Moreover, LVH has a high prevalence among our SPKT candidates, representing per se a harbinger of cardiovascular problems.5 In this setting, the negative effects of
small-vessel disease, enhanced by the presence of LVH, may have been responsible for ischemic ECG signs even with a CAD-negative angiographic study. The finding of an inverse relationship between LVH on TTE and the incidence of cardiac events was dismaying, being completely at variance with results in previous publications.5–7 While ECG signs of LVH seemed to correlate positively with the incidence of ischemic ECG alterations, none of these findings reached statistical significance. In addition, TTE and ECG detection of LVH poorly correlate and may actually be indicators of different aspects of the phenomenon.11,12 The lack of statistical significance of all results, and the paradoxical finding regarding LVH correlation with cardiac events, may be attributed to the small sample size. Larger series are needed to increase the power of the study. Medium- and long-term follow-up studies are also warranted to evaluate the real benefits of preoperative selection and successful SPKT on patient survival rates.
CONCLUSION
Preoperative evaluation with coronary angiography has possibly played a role in the absence of cardiac mortality and the low, relatively minor cardiac morbidity observed in our series in the perioperative period after SPKT. Although not statistically significant, the incidence of ischemic ECG appearances seems to correlate with the presence of CAD on preoperative angiograms, while LVH detected by TTE failed to show such a correlation. Our results may have been negatively affected by the small size of the sample, thus warranting further investigations to validate these observations. Finally, medium- and long-term follow-up studies are needed to evaluate the effects of preoperative selection on long-term posttransplant cardiac events and survival rates.
CARDIAC PERIOPERATIVE COMPLICATIONS
REFERENCES 1. Kannel WB, McGee DL: Diabetes and cardiovascular disease. The Framingham study. JAMA 241:2035, 1979 2. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus: Report of the Expert Committee on the diagnosis and classification of Diabetes Mellitus. Diabetes Care 20: 1183, 1997 3. Moss SE, Klein R, Klein BEK, et al: The association of glycemia and cause-specific mortality in a diabetic population. Arch Intern Med 154:2473, 1994 4. Stratta RJ, Taylor RJ, Gill IS: Pancreas transplantation: a managed cure approach to diabetes. Current Problems in Surgery 33:713, 1996 5. Messerli FH, Devereux RB: Left ventricular hypertrophy— good or evil? Am J Med 75:1, 1983 6. Kannel WB: Left ventricular hypertrophy as a risk factor in arterial hypertension. Eur Heart J 13(Suppl D):82, 1992
585 7. Bikkina M, Larson MG, Levy D: Asymptomatic ventricular arrhythmias and mortality risk in subjects with left ventricular hypertrophy. J Am Coll Cardiol 22:1111, 1993 8. Schweitzer EJ, Anderson L, Kuo PC: Safe pancreas transplantation in patients with coronary artery disease. Transplantation 63:1294, 1997 9. Nicolino A, Longobardi G, Furgi G: Left ventricular diastolic filling in diabetes mellitus with and without hypertension. Am J Hypertens 8:382, 1995 10. Illan F, Valdes-Chiavarri M, Tebar J: Anatomical and functional cardiac abnormalities in type 1 diabetes. Clin Investig 70:403, 1992 11. Kannel WB, Dannenberg AL, Levy D: Population implications of ECG left ventricular hypertrophy. Am J Cardiol 60:851, 1987 12. Levy D, Anderson KM, Savage DD, et al: Echocardiographically detected left ventricular hypertrophy, prevalence and risk factors. The Framingham Heart Study. Ann Intern Med 108:2, 1988