© 2014 Wiley Periodicals, Inc.
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ORIGINAL ARTICLE _____________________________________________________________
Left Main Disease Progression Following Left Branch Vessel Percutaneous Intervention in Patients Who Are Referred for Coronary Artery Bypass Grafting Mario Castillo-Sang, M.D., Melissa M. Anastacio, M.D., Tracey J. Guthrie, R.N, M.H.S., Hersh S. Maniar, M.D., Marc R. Moon, M.D., Michael K. Pasque, M.D., Ralph J. Damiano, M.D., and Jennifer S. Lawton, M.D. Department of Surgery, Division of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, Missouri ABSTRACT Background and Aim of the Study: We studied patients presenting for coronary artery bypass grafting (CABG) with significant left main coronary artery disease (LMD) despite previously documented minimal or no LMD at percutaneous coronary intervention (PCI) for left-sided branch coronary artery disease. Methods: Patients undergoing CABG for LMD with previous PCI were separated into fast or slow stenosis progression using percent change in LMD from first PCI to CABG divided by time (progression velocity). Outcomes and Kaplan–Meier survival were compared between the two groups. Results: Between September 1997 and June 2010, 4837 patients underwent CABG with 1235 of them having previous PCI of which 118 had LMD and previous left-sided branch PCI. Using median progression velocity fast and slow progression groups were identified (0.53 W 0.18 and 4.5 W 4.8%/month, p < 0.001). Mean follow-up was 4.9 W 3.6 years and 6.9 W 3.9 years, respectively. Fast progression patients were younger (p = 0.042), with higher baseline LMD at PCI (16.4% vs. 9% stenosis, p = 0.025), and a mean of 2.5 years to LMD compared to 10.6 years for the slow group (p < 0.001). There was no difference between the groups in number or type of PCI and number or type of vessel intervened. Kaplan–Meier survival was similar at one, three, and five years. Conclusions: Fast LMD progression patients were younger and made up 4.7% (59/1235) of patients undergoing CABG with a history of PCI. Rapid progression was not related to number, type of PCI, or branch vessel intervened. doi: 10.1111/jocs.12460 (J Card Surg 2015;30:35–40) Data on progression of left main disease (LMD) after percutaneous coronary intervention (PCI) is scant and derives from case reports and small studies.1–4 In one study using angiographic analysis of patients who
Presented at the American Heart Association Scientific Sessions, Los Angeles, CA, November 2012. Conflict of interest: The authors acknowledge no conflict of interest in the submission. Disclosures: none. The present address of Mario Castillo-Sang M.D. is Department of Surgery, Division of Cardiothoracic Surgery Medical University of South Carolina, Charleston, South Carolina Address for correspondence: Jennifer S. Lawton, M.D., Professor of Surgery, Division of Cardiothoracic Surgery, Washington University School of Medicine, 660 S. Euclid Ave., Campus Box 8234, St. Louis, MO 63110. Fax: 314-747-4216; e-mail: [email protected]
underwent percutaneous transluminal coronary angioplasty (PTCA), Kells et al.1 demonstrated a 1.7% incidence of significant LMD progression after PTCA. It is unknown if this form of LMD is more aggressive and, hence, has a higher morbidity and/or mortality after coronary artery bypass grafting surgery (CABG) than de novo LMD without preceding PCI. We suspected that PCI may lead to more rapid progression. Our study evaluated demographic and procedural characteristics of patients with progression of LMD following PCI for left-sided lesions and their outcomes after CABG. MATERIALS AND METHODS After institutional Institutional Review Board approval we evaluated progression of LMD in patients undergoing CABG for LMD with one or more previous PCI (intravascular ultrasound, angioplasty, cutting balloon,
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CASTILLO-SANG, ET AL. PROGRESSION OF LEFT MAIN DISEASE
atherectomy, stent) for left branch-vessel disease between September 1997 and June 2010. A retrospective review was carried out collecting demographic data, medications, and intervention details. The Social Security Death Index Database was utilized to ascertain living or dead status for all patients. Patients who underwent concomitant procedures, right-sided PCI only, had prior CABG, or who had incomplete data were excluded from the analysis. The degrees of LMD at the time of the very first left branch PCI and of the last catheterization preceding CABG were recorded. Initial baseline LMD was established using the data from the very first PCI. Initial LMD description was obtained from procedure reports and given that percentage and qualitative descriptions of LMD were provided we created three categories: ‘‘mild stenosis’’ for 0% to 39% and labeled 0%; ‘‘moderate stenosis’’ for 40% to 69% and labeled as 40%; ‘‘severe stenosis’’ for 70% or higher and labeled as 70%. The difference in percentage of LMD at the two points in time divided by the time interval in months defined the progression velocity (PV; percentage change in stenosis/months of progression). The median PV was used to categorize patients as fast or slow stenosis progression. Continuous variables are expressed as mean SD or as median with interquartile range (IQR: 25% to 75%) where data are skewed and categorical variables are expressed as frequencies and percentages. Categorical outcomes were compared using either the X2 or Fisher’s exact test, and continuous outcomes were compared using the t test for means of normally distributed continuous variables and Wilcoxon ranksum nonparametric test for skewed distributions. Kaplan–Meier method was used to estimate survival. All data analyses were done using SPSS (SPSS 20.0 for Windows; SPSS Inc., Chicago, IL, USA). RESULTS Between September 1997 and June 2010, 4837 patients underwent isolated CABG at a tertiary care institution and 1235 of them had a previous PCI. Two hundred sixty three of these patients were operated for severe LMD and 118 of them had prior isolated left branch vessel PCI and were the focus of the present study (Fig. 1). Among 1235 patients with a history of any PCI 263 were operated for severe LMD and 118 of them had previous isolated left sided branch PCI. In other words, when considering only those patients with leftsided branch PCI left main stenosis progression occurred in 9.6% (118/1235) of patients that had any form of preceding PCI (right or left). The majority of the 118 patients that showed LMD progression following left-sided PCI were males (72.0% 85/118) and their mean age was 65.0 11.9 years (Table 2). At their first PCI the mean LMD stenosis for all patients was 12.7%, while at CABG the mean LMD stenosis was 70.5% (mean percentage change of 57.7%) over a mean progression time of 79.2 months for a mean PV of 2.5%/month (Table 1). Left main stenosis at first catheterization was distributed as
J CARD SURG 2015;30:35–40
Figure 1. Determination of the study cohort. All isolated CABG procedures between 1/1997 and 6/2010 were included. The study cohort consisted of 118 patients with progression of LMD after left-sided branch vessel PCI. PCI, percutaneous coronary intervention; LMD, left main coronary artery disease; CABG, coronary artery bypass grafting.
follows: 69 patients had 0% left main stenosis; 12 patients with 10% stenosis; five patients with 20% stenosis; nine patients with 30% stenosis; 15 patients with 40% stenosis; six patients with 50% stenosis, and two patients with 60% stenosis. Using the median PV (0.9%/month) patients were grouped into slow and fast progression groups. There were 59 slow progression and 59 fast progression patients with 4.9 þ 3.6 years and 6.9 þ 3.9 years follow-up, respectively. Fast progression patients comprised 1.2% (59/4837 patients) of all CABG patients in that time period. Patients underwent isolated coronary revascularization without valvular interventions. The average number of diseased vessels at the time of surgery was three, with 96 patients having left anterior descending lesions; 64 having circumflex lesions; and 90 having right coronary lesions. Elective cases made up 78% (92/118) of cases while urgent and emergent cases made up 13% (15/118) and 9% (11/118) of cases. Fast progression group patients had a mean of 2.5 years from first PCI to CABG compared to 10.6 years for slow progression patients (p < 0.001). Fast progression patients were younger (p ¼ 0.042) and had a trend toward less renal failure (p ¼ 0.061) and less dyslipidemia (p ¼ 0.057). Fast progression group patients also had higher baseline LMD at first PCI (16.4% vs. 9%, p ¼ 0.025). The incidence of smoking, diabetes mellitus, peripheral vascular disease, hypertension, and cerebrovascular disease or statin use were not different between the two cohorts despite the age difference (Table 2). A total of 387 PCIs were performed in 118 patients with LMD progression (mean of 3.3 1.7 procedures per patient). Among the 118 study patients, 39.8% had two PCI procedures, 31.4% had three, 11.9% had four, and 16.9% had five or more PCI procedures. There
J CARD SURG 2015;30:35–40
CASTILLO-SANG, ET AL. PROGRESSION OF LEFT MAIN DISEASE
37
TABLE 1 PCI Characteristics of 118 Patients Who Underwent CABG for LMD Progression Following Left-Sided Branch Vessel PCI PCI Characteristics LMD at first PCI (%) LMD at surgery (%) Mean increase in LMD (%) Time from first PCI to CABG (years) Progression (months) Progression velocity (%/month) Total # PCI procedures Mean # PCI procedures/patient Distribution 2 procedures 3 procedures 4 procedures 5 procedures 6 procedures >6 procedures Number of vessels addressed at PCI 1 vessel 2 vessels 3 vessels Type of vessels addressed at PCI Left Main (all IVUS) LAD Left circumflex Both LAD and circumflex
All Patients (N = 118)
Slow Progression Cohort (N = 59)
Fast Progression Cohort (N = 59)
P-Value
12.7 18.1 70.5 10.3 57.7 20.8 6.5 5.8
9.0 15.8 70.1 10.5 61.0 18.3 10.6 5.3
16.4 19.5 70.8 10.1 54.3 22.7 2.5 2.5
0.025 0.742 0.082
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ORIGINAL ARTICLE _____________________________________________________________
Left Main Disease Progression Following Left Branch Vessel Percutaneous Intervention in Patients Who Are Referred for Coronary Artery Bypass Grafting Mario Castillo-Sang, M.D., Melissa M. Anastacio, M.D., Tracey J. Guthrie, R.N, M.H.S., Hersh S. Maniar, M.D., Marc R. Moon, M.D., Michael K. Pasque, M.D., Ralph J. Damiano, M.D., and Jennifer S. Lawton, M.D. Department of Surgery, Division of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, Missouri ABSTRACT Background and Aim of the Study: We studied patients presenting for coronary artery bypass grafting (CABG) with significant left main coronary artery disease (LMD) despite previously documented minimal or no LMD at percutaneous coronary intervention (PCI) for left-sided branch coronary artery disease. Methods: Patients undergoing CABG for LMD with previous PCI were separated into fast or slow stenosis progression using percent change in LMD from first PCI to CABG divided by time (progression velocity). Outcomes and Kaplan–Meier survival were compared between the two groups. Results: Between September 1997 and June 2010, 4837 patients underwent CABG with 1235 of them having previous PCI of which 118 had LMD and previous left-sided branch PCI. Using median progression velocity fast and slow progression groups were identified (0.53 W 0.18 and 4.5 W 4.8%/month, p < 0.001). Mean follow-up was 4.9 W 3.6 years and 6.9 W 3.9 years, respectively. Fast progression patients were younger (p = 0.042), with higher baseline LMD at PCI (16.4% vs. 9% stenosis, p = 0.025), and a mean of 2.5 years to LMD compared to 10.6 years for the slow group (p < 0.001). There was no difference between the groups in number or type of PCI and number or type of vessel intervened. Kaplan–Meier survival was similar at one, three, and five years. Conclusions: Fast LMD progression patients were younger and made up 4.7% (59/1235) of patients undergoing CABG with a history of PCI. Rapid progression was not related to number, type of PCI, or branch vessel intervened. doi: 10.1111/jocs.12460 (J Card Surg 2015;30:35–40) Data on progression of left main disease (LMD) after percutaneous coronary intervention (PCI) is scant and derives from case reports and small studies.1–4 In one study using angiographic analysis of patients who
Presented at the American Heart Association Scientific Sessions, Los Angeles, CA, November 2012. Conflict of interest: The authors acknowledge no conflict of interest in the submission. Disclosures: none. The present address of Mario Castillo-Sang M.D. is Department of Surgery, Division of Cardiothoracic Surgery Medical University of South Carolina, Charleston, South Carolina Address for correspondence: Jennifer S. Lawton, M.D., Professor of Surgery, Division of Cardiothoracic Surgery, Washington University School of Medicine, 660 S. Euclid Ave., Campus Box 8234, St. Louis, MO 63110. Fax: 314-747-4216; e-mail: [email protected]
underwent percutaneous transluminal coronary angioplasty (PTCA), Kells et al.1 demonstrated a 1.7% incidence of significant LMD progression after PTCA. It is unknown if this form of LMD is more aggressive and, hence, has a higher morbidity and/or mortality after coronary artery bypass grafting surgery (CABG) than de novo LMD without preceding PCI. We suspected that PCI may lead to more rapid progression. Our study evaluated demographic and procedural characteristics of patients with progression of LMD following PCI for left-sided lesions and their outcomes after CABG. MATERIALS AND METHODS After institutional Institutional Review Board approval we evaluated progression of LMD in patients undergoing CABG for LMD with one or more previous PCI (intravascular ultrasound, angioplasty, cutting balloon,
36
CASTILLO-SANG, ET AL. PROGRESSION OF LEFT MAIN DISEASE
atherectomy, stent) for left branch-vessel disease between September 1997 and June 2010. A retrospective review was carried out collecting demographic data, medications, and intervention details. The Social Security Death Index Database was utilized to ascertain living or dead status for all patients. Patients who underwent concomitant procedures, right-sided PCI only, had prior CABG, or who had incomplete data were excluded from the analysis. The degrees of LMD at the time of the very first left branch PCI and of the last catheterization preceding CABG were recorded. Initial baseline LMD was established using the data from the very first PCI. Initial LMD description was obtained from procedure reports and given that percentage and qualitative descriptions of LMD were provided we created three categories: ‘‘mild stenosis’’ for 0% to 39% and labeled 0%; ‘‘moderate stenosis’’ for 40% to 69% and labeled as 40%; ‘‘severe stenosis’’ for 70% or higher and labeled as 70%. The difference in percentage of LMD at the two points in time divided by the time interval in months defined the progression velocity (PV; percentage change in stenosis/months of progression). The median PV was used to categorize patients as fast or slow stenosis progression. Continuous variables are expressed as mean SD or as median with interquartile range (IQR: 25% to 75%) where data are skewed and categorical variables are expressed as frequencies and percentages. Categorical outcomes were compared using either the X2 or Fisher’s exact test, and continuous outcomes were compared using the t test for means of normally distributed continuous variables and Wilcoxon ranksum nonparametric test for skewed distributions. Kaplan–Meier method was used to estimate survival. All data analyses were done using SPSS (SPSS 20.0 for Windows; SPSS Inc., Chicago, IL, USA). RESULTS Between September 1997 and June 2010, 4837 patients underwent isolated CABG at a tertiary care institution and 1235 of them had a previous PCI. Two hundred sixty three of these patients were operated for severe LMD and 118 of them had prior isolated left branch vessel PCI and were the focus of the present study (Fig. 1). Among 1235 patients with a history of any PCI 263 were operated for severe LMD and 118 of them had previous isolated left sided branch PCI. In other words, when considering only those patients with leftsided branch PCI left main stenosis progression occurred in 9.6% (118/1235) of patients that had any form of preceding PCI (right or left). The majority of the 118 patients that showed LMD progression following left-sided PCI were males (72.0% 85/118) and their mean age was 65.0 11.9 years (Table 2). At their first PCI the mean LMD stenosis for all patients was 12.7%, while at CABG the mean LMD stenosis was 70.5% (mean percentage change of 57.7%) over a mean progression time of 79.2 months for a mean PV of 2.5%/month (Table 1). Left main stenosis at first catheterization was distributed as
J CARD SURG 2015;30:35–40
Figure 1. Determination of the study cohort. All isolated CABG procedures between 1/1997 and 6/2010 were included. The study cohort consisted of 118 patients with progression of LMD after left-sided branch vessel PCI. PCI, percutaneous coronary intervention; LMD, left main coronary artery disease; CABG, coronary artery bypass grafting.
follows: 69 patients had 0% left main stenosis; 12 patients with 10% stenosis; five patients with 20% stenosis; nine patients with 30% stenosis; 15 patients with 40% stenosis; six patients with 50% stenosis, and two patients with 60% stenosis. Using the median PV (0.9%/month) patients were grouped into slow and fast progression groups. There were 59 slow progression and 59 fast progression patients with 4.9 þ 3.6 years and 6.9 þ 3.9 years follow-up, respectively. Fast progression patients comprised 1.2% (59/4837 patients) of all CABG patients in that time period. Patients underwent isolated coronary revascularization without valvular interventions. The average number of diseased vessels at the time of surgery was three, with 96 patients having left anterior descending lesions; 64 having circumflex lesions; and 90 having right coronary lesions. Elective cases made up 78% (92/118) of cases while urgent and emergent cases made up 13% (15/118) and 9% (11/118) of cases. Fast progression group patients had a mean of 2.5 years from first PCI to CABG compared to 10.6 years for slow progression patients (p < 0.001). Fast progression patients were younger (p ¼ 0.042) and had a trend toward less renal failure (p ¼ 0.061) and less dyslipidemia (p ¼ 0.057). Fast progression group patients also had higher baseline LMD at first PCI (16.4% vs. 9%, p ¼ 0.025). The incidence of smoking, diabetes mellitus, peripheral vascular disease, hypertension, and cerebrovascular disease or statin use were not different between the two cohorts despite the age difference (Table 2). A total of 387 PCIs were performed in 118 patients with LMD progression (mean of 3.3 1.7 procedures per patient). Among the 118 study patients, 39.8% had two PCI procedures, 31.4% had three, 11.9% had four, and 16.9% had five or more PCI procedures. There
J CARD SURG 2015;30:35–40
CASTILLO-SANG, ET AL. PROGRESSION OF LEFT MAIN DISEASE
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TABLE 1 PCI Characteristics of 118 Patients Who Underwent CABG for LMD Progression Following Left-Sided Branch Vessel PCI PCI Characteristics LMD at first PCI (%) LMD at surgery (%) Mean increase in LMD (%) Time from first PCI to CABG (years) Progression (months) Progression velocity (%/month) Total # PCI procedures Mean # PCI procedures/patient Distribution 2 procedures 3 procedures 4 procedures 5 procedures 6 procedures >6 procedures Number of vessels addressed at PCI 1 vessel 2 vessels 3 vessels Type of vessels addressed at PCI Left Main (all IVUS) LAD Left circumflex Both LAD and circumflex
All Patients (N = 118)
Slow Progression Cohort (N = 59)
Fast Progression Cohort (N = 59)
P-Value
12.7 18.1 70.5 10.3 57.7 20.8 6.5 5.8
9.0 15.8 70.1 10.5 61.0 18.3 10.6 5.3
16.4 19.5 70.8 10.1 54.3 22.7 2.5 2.5
0.025 0.742 0.082
