Cardiothoracic

FT. LAUDERDALE, FLA – Early repair – within one week – of acquired ventral septal defect in patients with myocardial infarction was associated with a significantly higher mortality rate than was later repair in a retrospective review.

Acquired ventral septal defect (VSD), a relatively rare but devastating complication of myocardial infarction, frequently leads to cardiogenic shock and death. Surgical repair is generally required, although there is a high mortality.

To identify risk factors for poor patient outcomes, a study of the Society for Thoracic Surgeons National Database was performed to characterize patients undergoing post-MI VSD surgical repair, Dr. George J. Arnaoutakis said at the annual meeting of the Society of Thoracic Surgeons.

This retrospective review identified all adults (patients greater than 18 years of age) who underwent post-MI VSD repair between 1999 and 2010. The primary outcome measure was operative mortality and patients with congenital VSD were excluded.

"This largest to date study examining post-MI VSD repair was done in part to provide a surgical benchmark for future comparisons as percutaneous closure devices emerge to treat this condition," noted Dr. Arnaoutakis of the division of cardiac surgery at Johns Hopkins University, Baltimore.

The demographics of the 2,876 patients included in the study were a mean age of 68 years; 56.5% of the patients were men; and 7.5% of patients had prior coronary artery bypass grafting (CABG) surgery. Operative characteristics included preoperative support with an intraaortic balloon pump (65%); urgent status (35%); emergent status (49.7%); and concomitant CABG (63.9%).

Timing of surgery was found to be an important predictor of risk, with 54% mortality occurring in patients who had repair less than 7 days after MI, and 18% mortality in those patients who had their surgery greater than 7 days after MI. Multivariate analysis also showed that the timing of MI with relation to VSD repair was independently associated with operative mortality.

Overall, major morbidity and mortality was high, at nearly 77%. Other surgical characteristics significantly associated with higher mortality included longer cardiopulmonary bypass time, preoperative dialysis, emergent surgery, and shock.

"Ventricular septal rupture remains a devastating complication after myocardial infarction," he said, with a shorter time interval between MI and surgical repair of the VSD, being highly associated with operative mortality, Dr Arnaoutakis summarized.

He did point out that one flaw in this study based on the STS Database was that it could not account for patients who died while waiting for VSD repair, which might influence the results. In addition the overall incidence of acquired VSD was too low to determine the effect of individual surgeon or center volume on mortality rates.

Dr. Arnaoutakis agreed with audience suggestions that given the high overall mortality rate of surgical VSD closure, perhaps consideration of the new percutaneous closure devices and the possibility of ventricular assist device support might be reasonable options.

Dr. Arnaoutakis reported having no financial conflicts. Another researcher on the project reported research support from HeartWare International Inc. and Thoratec Corp.

FT. LAUDERDALE, FLA – Early repair – within one week – of acquired ventral septal defect in patients with myocardial infarction was associated with a significantly higher mortality rate than was later repair in a retrospective review.

Acquired ventral septal defect (VSD), a relatively rare but devastating complication of myocardial infarction, frequently leads to cardiogenic shock and death. Surgical repair is generally required, although there is a high mortality.

To identify risk factors for poor patient outcomes, a study of the Society for Thoracic Surgeons National Database was performed to characterize patients undergoing post-MI VSD surgical repair, Dr. George J. Arnaoutakis said at the annual meeting of the Society of Thoracic Surgeons.

This retrospective review identified all adults (patients greater than 18 years of age) who underwent post-MI VSD repair between 1999 and 2010. The primary outcome measure was operative mortality and patients with congenital VSD were excluded.

"This largest to date study examining post-MI VSD repair was done in part to provide a surgical benchmark for future comparisons as percutaneous closure devices emerge to treat this condition," noted Dr. Arnaoutakis of the division of cardiac surgery at Johns Hopkins University, Baltimore.

The demographics of the 2,876 patients included in the study were a mean age of 68 years; 56.5% of the patients were men; and 7.5% of patients had prior coronary artery bypass grafting (CABG) surgery. Operative characteristics included preoperative support with an intraaortic balloon pump (65%); urgent status (35%); emergent status (49.7%); and concomitant CABG (63.9%).

Timing of surgery was found to be an important predictor of risk, with 54% mortality occurring in patients who had repair less than 7 days after MI, and 18% mortality in those patients who had their surgery greater than 7 days after MI. Multivariate analysis also showed that the timing of MI with relation to VSD repair was independently associated with operative mortality.

Overall, major morbidity and mortality was high, at nearly 77%. Other surgical characteristics significantly associated with higher mortality included longer cardiopulmonary bypass time, preoperative dialysis, emergent surgery, and shock.

"Ventricular septal rupture remains a devastating complication after myocardial infarction," he said, with a shorter time interval between MI and surgical repair of the VSD, being highly associated with operative mortality, Dr Arnaoutakis summarized.

He did point out that one flaw in this study based on the STS Database was that it could not account for patients who died while waiting for VSD repair, which might influence the results. In addition the overall incidence of acquired VSD was too low to determine the effect of individual surgeon or center volume on mortality rates.

Dr. Arnaoutakis agreed with audience suggestions that given the high overall mortality rate of surgical VSD closure, perhaps consideration of the new percutaneous closure devices and the possibility of ventricular assist device support might be reasonable options.

Dr. Arnaoutakis reported having no financial conflicts. Another researcher on the project reported research support from HeartWare International Inc. and Thoratec Corp.

FT. LAUDERDALE, FLA – Early repair – within one week – of acquired ventral septal defect in patients with myocardial infarction was associated with a significantly higher mortality rate than was later repair in a retrospective review.

Acquired ventral septal defect (VSD), a relatively rare but devastating complication of myocardial infarction, frequently leads to cardiogenic shock and death. Surgical repair is generally required, although there is a high mortality.

To identify risk factors for poor patient outcomes, a study of the Society for Thoracic Surgeons National Database was performed to characterize patients undergoing post-MI VSD surgical repair, Dr. George J. Arnaoutakis said at the annual meeting of the Society of Thoracic Surgeons.

This retrospective review identified all adults (patients greater than 18 years of age) who underwent post-MI VSD repair between 1999 and 2010. The primary outcome measure was operative mortality and patients with congenital VSD were excluded.

"This largest to date study examining post-MI VSD repair was done in part to provide a surgical benchmark for future comparisons as percutaneous closure devices emerge to treat this condition," noted Dr. Arnaoutakis of the division of cardiac surgery at Johns Hopkins University, Baltimore.

The demographics of the 2,876 patients included in the study were a mean age of 68 years; 56.5% of the patients were men; and 7.5% of patients had prior coronary artery bypass grafting (CABG) surgery. Operative characteristics included preoperative support with an intraaortic balloon pump (65%); urgent status (35%); emergent status (49.7%); and concomitant CABG (63.9%).

Timing of surgery was found to be an important predictor of risk, with 54% mortality occurring in patients who had repair less than 7 days after MI, and 18% mortality in those patients who had their surgery greater than 7 days after MI. Multivariate analysis also showed that the timing of MI with relation to VSD repair was independently associated with operative mortality.

Overall, major morbidity and mortality was high, at nearly 77%. Other surgical characteristics significantly associated with higher mortality included longer cardiopulmonary bypass time, preoperative dialysis, emergent surgery, and shock.

"Ventricular septal rupture remains a devastating complication after myocardial infarction," he said, with a shorter time interval between MI and surgical repair of the VSD, being highly associated with operative mortality, Dr Arnaoutakis summarized.

He did point out that one flaw in this study based on the STS Database was that it could not account for patients who died while waiting for VSD repair, which might influence the results. In addition the overall incidence of acquired VSD was too low to determine the effect of individual surgeon or center volume on mortality rates.

Dr. Arnaoutakis agreed with audience suggestions that given the high overall mortality rate of surgical VSD closure, perhaps consideration of the new percutaneous closure devices and the possibility of ventricular assist device support might be reasonable options.

Dr. Arnaoutakis reported having no financial conflicts. Another researcher on the project reported research support from HeartWare International Inc. and Thoratec Corp.

Intravenous cangrelor may prove to be a useful "bridge" in patients awaiting nonemergency CABG who must first discontinue their regular antiplatelet therapy, according to the results of the Maintenance of Platelet Inhibition With Cangrelor (BRIDGE) trial reported in the Jan. 18 issue of JAMA.

The practice of discontinuation of antiplatelet therapy is associated with significant morbidity and mortality; in patients who have coronary stents, it raises the risk of stent thrombosis that often leads to myocardial infarction and death.

"Cessation of thienopyridine treatment for nearly a week before surgery, with patients not hospitalized or monitored but carrying an excess risk of major ischemic events, has been a troubling and not infrequent problem for clinicians, because it is estimated that approximately 5% of patients will require some type of surgery within the first 12 months after stent implant or [acute coronary syndrome] diagnosis," said Dr. Dominick J. Angiolillo of the department of cardiology, University of Florida, Jacksonville, and his associates.

In this multicenter clinical trial sponsored by the drug’s maker, cangrelor "achieved and maintained target levels of platelet inhibition known to be associated with a low risk of thrombotic events compared with placebo, without a significant excess in bleeding complications," the investigators noted.

Cangrelor is an investigational nonthienopyridine adenosine triphosphate analogue that acts as an antagonist of the P2Y12 receptor. It is characterized by "rapid, potent, predictable, and reversible platelet inhibition," and its extremely short half-life (3-6 minutes) allows "rapid offset of effect."

The investigators hypothesized that cangrelor would allow patients who must discontinue antiplatelet therapy prior to cardiac surgery, especially if they’re taking a P2Y12 inhibitor such as ticlopidine, clopidogrel, or prasugrel, to go off their usual drug without raising their risk for thrombotic events. They tested this hypothesis in a two-part trial.

The first part was an open-label dose-finding study involving 11 adults, which concluded that the optimal intravenous dose needed to maintain antiplatelet activity without raising bleeding risks was 0.75 mcg/kg per minute.

In the second part of the trial, 210 patients awaiting CABG at 34 medical centers around the world were randomly assigned to receive either cangrelor (106 subjects) or placebo (104 subjects) after thienopyridines were discontinued and throughout the preoperative period – that is, until 1-6 hours before surgical incision. Platelet function was assessed before, during, and after the infusion.

The mean interval between discontinuation of thienopyridines and infusion of the study drug was 29 hours, and the mean duration of the infusion was approximately 3 days.

The primary end point was the percentage of patients who showed platelet reactivity of less than 240 P2Y12 Reaction Units (PRUs) throughout the infusion of the study drug. "This level approximated the levels of platelet reactivity expected to be maintained if a thienopyridine had not been discontinued," the investigators explained.

This end point was met by 99% of the cangrelor group but only 19% of the placebo group. It was achieved independently of patients’ usual dose of thienopyridines and independently of the length of time since thienopyridines were discontinued, Dr. Angiolillo and his colleagues said (JAMA 2012;307:265-74).

Moreover, cangrelor did not raise the rate of excessive bleeding related to CABG surgery. This safety end point occurred in 22 patients: 11.8% of the cangrelor group and 10.4% of the placebo group, a nonsignificant difference.

The number of minor bleeding events was numerically higher with cangrelor but did not reach statistical significance. Other adverse events, including dyspnea and laboratory abnormalities, also were comparable between the two groups. This favorable safety profile, even with prolonged infusion of up to 7 days, was "reassuring," the researchers noted.

Ischemic end points prior to surgery were low in both groups, occurring in 2.8% (3 of 106) and 4.0% (4 of 101) of patients in the cangrelor and placebo groups.

"These observations support the hypothesis that intravenous cangrelor is a feasible management strategy, providing prolonged platelet P2Y12 inhibition in patients who must wait for cardiac surgery after thienopyridine discontinuation," they said.

This study was sponsored by the Medicines Company. Dr. Angiolillo reported ties to Bristol-Myers Squibb, Sanofi-Aventis, Eli Lilly, Daiichi Sankyo, AstraZeneca, Portola, Novartis, Medicure, Accumetrics, Arena Pharmaceuticals, Merck, Evolva, and Abbott Vascular, and his associates reported ties to numerous other industry sources.

Intravenous cangrelor may prove to be a useful "bridge" in patients awaiting nonemergency CABG who must first discontinue their regular antiplatelet therapy, according to the results of the Maintenance of Platelet Inhibition With Cangrelor (BRIDGE) trial reported in the Jan. 18 issue of JAMA.

The practice of discontinuation of antiplatelet therapy is associated with significant morbidity and mortality; in patients who have coronary stents, it raises the risk of stent thrombosis that often leads to myocardial infarction and death.

"Cessation of thienopyridine treatment for nearly a week before surgery, with patients not hospitalized or monitored but carrying an excess risk of major ischemic events, has been a troubling and not infrequent problem for clinicians, because it is estimated that approximately 5% of patients will require some type of surgery within the first 12 months after stent implant or [acute coronary syndrome] diagnosis," said Dr. Dominick J. Angiolillo of the department of cardiology, University of Florida, Jacksonville, and his associates.

In this multicenter clinical trial sponsored by the drug’s maker, cangrelor "achieved and maintained target levels of platelet inhibition known to be associated with a low risk of thrombotic events compared with placebo, without a significant excess in bleeding complications," the investigators noted.

Cangrelor is an investigational nonthienopyridine adenosine triphosphate analogue that acts as an antagonist of the P2Y12 receptor. It is characterized by "rapid, potent, predictable, and reversible platelet inhibition," and its extremely short half-life (3-6 minutes) allows "rapid offset of effect."

The investigators hypothesized that cangrelor would allow patients who must discontinue antiplatelet therapy prior to cardiac surgery, especially if they’re taking a P2Y12 inhibitor such as ticlopidine, clopidogrel, or prasugrel, to go off their usual drug without raising their risk for thrombotic events. They tested this hypothesis in a two-part trial.

The first part was an open-label dose-finding study involving 11 adults, which concluded that the optimal intravenous dose needed to maintain antiplatelet activity without raising bleeding risks was 0.75 mcg/kg per minute.

In the second part of the trial, 210 patients awaiting CABG at 34 medical centers around the world were randomly assigned to receive either cangrelor (106 subjects) or placebo (104 subjects) after thienopyridines were discontinued and throughout the preoperative period – that is, until 1-6 hours before surgical incision. Platelet function was assessed before, during, and after the infusion.

The mean interval between discontinuation of thienopyridines and infusion of the study drug was 29 hours, and the mean duration of the infusion was approximately 3 days.

The primary end point was the percentage of patients who showed platelet reactivity of less than 240 P2Y12 Reaction Units (PRUs) throughout the infusion of the study drug. "This level approximated the levels of platelet reactivity expected to be maintained if a thienopyridine had not been discontinued," the investigators explained.

This end point was met by 99% of the cangrelor group but only 19% of the placebo group. It was achieved independently of patients’ usual dose of thienopyridines and independently of the length of time since thienopyridines were discontinued, Dr. Angiolillo and his colleagues said (JAMA 2012;307:265-74).

Moreover, cangrelor did not raise the rate of excessive bleeding related to CABG surgery. This safety end point occurred in 22 patients: 11.8% of the cangrelor group and 10.4% of the placebo group, a nonsignificant difference.

The number of minor bleeding events was numerically higher with cangrelor but did not reach statistical significance. Other adverse events, including dyspnea and laboratory abnormalities, also were comparable between the two groups. This favorable safety profile, even with prolonged infusion of up to 7 days, was "reassuring," the researchers noted.

Ischemic end points prior to surgery were low in both groups, occurring in 2.8% (3 of 106) and 4.0% (4 of 101) of patients in the cangrelor and placebo groups.

"These observations support the hypothesis that intravenous cangrelor is a feasible management strategy, providing prolonged platelet P2Y12 inhibition in patients who must wait for cardiac surgery after thienopyridine discontinuation," they said.

This study was sponsored by the Medicines Company. Dr. Angiolillo reported ties to Bristol-Myers Squibb, Sanofi-Aventis, Eli Lilly, Daiichi Sankyo, AstraZeneca, Portola, Novartis, Medicure, Accumetrics, Arena Pharmaceuticals, Merck, Evolva, and Abbott Vascular, and his associates reported ties to numerous other industry sources.

Intravenous cangrelor may prove to be a useful "bridge" in patients awaiting nonemergency CABG who must first discontinue their regular antiplatelet therapy, according to the results of the Maintenance of Platelet Inhibition With Cangrelor (BRIDGE) trial reported in the Jan. 18 issue of JAMA.

The practice of discontinuation of antiplatelet therapy is associated with significant morbidity and mortality; in patients who have coronary stents, it raises the risk of stent thrombosis that often leads to myocardial infarction and death.

"Cessation of thienopyridine treatment for nearly a week before surgery, with patients not hospitalized or monitored but carrying an excess risk of major ischemic events, has been a troubling and not infrequent problem for clinicians, because it is estimated that approximately 5% of patients will require some type of surgery within the first 12 months after stent implant or [acute coronary syndrome] diagnosis," said Dr. Dominick J. Angiolillo of the department of cardiology, University of Florida, Jacksonville, and his associates.

In this multicenter clinical trial sponsored by the drug’s maker, cangrelor "achieved and maintained target levels of platelet inhibition known to be associated with a low risk of thrombotic events compared with placebo, without a significant excess in bleeding complications," the investigators noted.

Cangrelor is an investigational nonthienopyridine adenosine triphosphate analogue that acts as an antagonist of the P2Y12 receptor. It is characterized by "rapid, potent, predictable, and reversible platelet inhibition," and its extremely short half-life (3-6 minutes) allows "rapid offset of effect."

The investigators hypothesized that cangrelor would allow patients who must discontinue antiplatelet therapy prior to cardiac surgery, especially if they’re taking a P2Y12 inhibitor such as ticlopidine, clopidogrel, or prasugrel, to go off their usual drug without raising their risk for thrombotic events. They tested this hypothesis in a two-part trial.

The first part was an open-label dose-finding study involving 11 adults, which concluded that the optimal intravenous dose needed to maintain antiplatelet activity without raising bleeding risks was 0.75 mcg/kg per minute.

In the second part of the trial, 210 patients awaiting CABG at 34 medical centers around the world were randomly assigned to receive either cangrelor (106 subjects) or placebo (104 subjects) after thienopyridines were discontinued and throughout the preoperative period – that is, until 1-6 hours before surgical incision. Platelet function was assessed before, during, and after the infusion.

The mean interval between discontinuation of thienopyridines and infusion of the study drug was 29 hours, and the mean duration of the infusion was approximately 3 days.

The primary end point was the percentage of patients who showed platelet reactivity of less than 240 P2Y12 Reaction Units (PRUs) throughout the infusion of the study drug. "This level approximated the levels of platelet reactivity expected to be maintained if a thienopyridine had not been discontinued," the investigators explained.

This end point was met by 99% of the cangrelor group but only 19% of the placebo group. It was achieved independently of patients’ usual dose of thienopyridines and independently of the length of time since thienopyridines were discontinued, Dr. Angiolillo and his colleagues said (JAMA 2012;307:265-74).

Moreover, cangrelor did not raise the rate of excessive bleeding related to CABG surgery. This safety end point occurred in 22 patients: 11.8% of the cangrelor group and 10.4% of the placebo group, a nonsignificant difference.

The number of minor bleeding events was numerically higher with cangrelor but did not reach statistical significance. Other adverse events, including dyspnea and laboratory abnormalities, also were comparable between the two groups. This favorable safety profile, even with prolonged infusion of up to 7 days, was "reassuring," the researchers noted.

Ischemic end points prior to surgery were low in both groups, occurring in 2.8% (3 of 106) and 4.0% (4 of 101) of patients in the cangrelor and placebo groups.

"These observations support the hypothesis that intravenous cangrelor is a feasible management strategy, providing prolonged platelet P2Y12 inhibition in patients who must wait for cardiac surgery after thienopyridine discontinuation," they said.

This study was sponsored by the Medicines Company. Dr. Angiolillo reported ties to Bristol-Myers Squibb, Sanofi-Aventis, Eli Lilly, Daiichi Sankyo, AstraZeneca, Portola, Novartis, Medicure, Accumetrics, Arena Pharmaceuticals, Merck, Evolva, and Abbott Vascular, and his associates reported ties to numerous other industry sources.

SAN FRANCISCO – Hepatitis E is an uncommon but often serious infection in immunosuppressed heart transplant recipients that warrants routine screening, according to investigators at Erasmus University Medical Center in Rotterdam, the Netherlands.

In a study of 263 recipients, 3% were found to have become infected with hepatitis E, most with symptomatic chronic disease. The infections ranged in severity from mild, transient viremia to severe and possibly progressive hepatitis with marked steatosis on liver biopsy.

"Chronic hepatitis E virus infection can have serious consequences in this group of patients," Dr. Annemiek A. van der Eijk said in presenting the findings at the annual meeting of the American Association for the Study of Liver Diseases (AASLD). "We advise systematic hepatitis E virus RNA screening in solid organ transplant recipients. In cases in which liver enzymes are increased, additional hepatitis E virus screening should be implemented."

"Chronic hepatitis E virus infection ... is a treatable disease," she added. Some patients were able to clear the virus when their immunosuppressants were tapered, but doing so also sometimes triggered rejection, which necessitated a resumption of therapy. "In our center, we are now treating patients with ribavirin (Copegus, Rebetol), but there are no large, randomized, controlled trials about the dose and duration of therapy."

"We advise systematic hepatitis E virus RNA screening in solid organ transplant recipients."

Importantly, she stressed, physicians should include hepatitis E infection in the differential diagnosis when transplant recipients have signs and symptoms of liver dysfunction, as it could be mistaken for a variety of other conditions having distinctly different treatments.

Chronicity "is not something we often associate with hepatitis E; it really doesn’t cause chronic infection like hepatitis B or C. But in this kind of immunosuppressed situation, it could," commented Dr. T. Jake Liang, president of the AASLD and chief of the Liver Diseases Branch at the National Institute of Diabetes and Digestive and Kidney Diseases.

"This [study] makes us aware of another cause of chronic liver disease, especially in people who are immunosuppressed, or receiving chemotherapy, or undergoing transplantation with lifelong immunosuppression," he said in a press conference.

Hepatitis E is transmitted mainly by the fecal-oral route (especially through contaminated water) but it can also be acquired by consuming raw or undercooked meat, through parenteral and vertical transmission, and – rarely – by person-to-person contact.

Swine are known to carry the virus. "In the Netherlands, more than 50% of the pig population is infected with hepatitis E virus, and 7% of the livers sold in supermarkets are hepatitis E virus RNA positive," Dr. van der Eijk noted.

Infection is especially worrisome in immunocompromised patients, as they can develop persistent elevation of liver enzymes and chronic hepatitis, with some reports also suggesting the possibility of rapid progression to cirrhosis.

In a cross-sectional study, the investigators tested serum samples from orthotopic heart transplant recipients at the center who were alive in 2010 and 2011 and had banked serum. The patients were receiving tacrolimus (Prograf)- and prednisolone-based immunosuppression.

Samples were tested by both polymerase chain reaction (PCR) for viral RNA – which was used to define infection – and serologic assays for antibodies to the virus. "We decided to screen all of our patients with PCR because we know serology outcomes differ greatly between the different tests used," Dr. van der Eijk explained.

Overall, 7 of the 263 patients studied were found to be infected with hepatitis E virus, for a point prevalence of 3%, and six of them had chronic infection (defined as PCR positivity for more than 6 months). The six men and one woman had a median age of 53 years. Retrospective serum testing showed that the time between transplantation and infection was a median of 8 years, but it ranged widely, from 1 to 20 years.

Viral genotyping showed that all of the patients were infected with genotype 3, which is associated with sporadic cases of hepatitis E in Western countries unrelated to travel and is likely of swine origin. Phylogenetic testing showed no evidence that the infections shared a common source or were acquired nosocomially.

Only two patients had virus-specific IgM antibodies at the time of initial PCR-detected infection and, on average, the PCR became positive 143 days before IgM antibodies were detectable. Thus, "PCR is superior [to serology] to detect infection in immunocompromised patients," Dr. van der Eijk commented.

The patients with chronic infection had elevations to varying extents of alanine aminotransferase levels, gamma-glutamyl transferase levels, or both. On liver biopsy, their Histologic Activity Index scores also ranged considerably, but three patients had scores of 10, indicating moderate disease, with features such as hepatocyte degeneration and fibrosis.

Although all of the patients with chronic hepatitis E had fecal shedding of the virus, none of their spouses was found to be infected on either serologic or PCR testing.

Dr. van der Eijk and Dr. Liang reported that they had no relevant conflicts of interest.

SAN FRANCISCO – Hepatitis E is an uncommon but often serious infection in immunosuppressed heart transplant recipients that warrants routine screening, according to investigators at Erasmus University Medical Center in Rotterdam, the Netherlands.

In a study of 263 recipients, 3% were found to have become infected with hepatitis E, most with symptomatic chronic disease. The infections ranged in severity from mild, transient viremia to severe and possibly progressive hepatitis with marked steatosis on liver biopsy.

"Chronic hepatitis E virus infection can have serious consequences in this group of patients," Dr. Annemiek A. van der Eijk said in presenting the findings at the annual meeting of the American Association for the Study of Liver Diseases (AASLD). "We advise systematic hepatitis E virus RNA screening in solid organ transplant recipients. In cases in which liver enzymes are increased, additional hepatitis E virus screening should be implemented."

"Chronic hepatitis E virus infection ... is a treatable disease," she added. Some patients were able to clear the virus when their immunosuppressants were tapered, but doing so also sometimes triggered rejection, which necessitated a resumption of therapy. "In our center, we are now treating patients with ribavirin (Copegus, Rebetol), but there are no large, randomized, controlled trials about the dose and duration of therapy."

"We advise systematic hepatitis E virus RNA screening in solid organ transplant recipients."

Importantly, she stressed, physicians should include hepatitis E infection in the differential diagnosis when transplant recipients have signs and symptoms of liver dysfunction, as it could be mistaken for a variety of other conditions having distinctly different treatments.

Chronicity "is not something we often associate with hepatitis E; it really doesn’t cause chronic infection like hepatitis B or C. But in this kind of immunosuppressed situation, it could," commented Dr. T. Jake Liang, president of the AASLD and chief of the Liver Diseases Branch at the National Institute of Diabetes and Digestive and Kidney Diseases.

"This [study] makes us aware of another cause of chronic liver disease, especially in people who are immunosuppressed, or receiving chemotherapy, or undergoing transplantation with lifelong immunosuppression," he said in a press conference.

Hepatitis E is transmitted mainly by the fecal-oral route (especially through contaminated water) but it can also be acquired by consuming raw or undercooked meat, through parenteral and vertical transmission, and – rarely – by person-to-person contact.

Swine are known to carry the virus. "In the Netherlands, more than 50% of the pig population is infected with hepatitis E virus, and 7% of the livers sold in supermarkets are hepatitis E virus RNA positive," Dr. van der Eijk noted.

Infection is especially worrisome in immunocompromised patients, as they can develop persistent elevation of liver enzymes and chronic hepatitis, with some reports also suggesting the possibility of rapid progression to cirrhosis.

In a cross-sectional study, the investigators tested serum samples from orthotopic heart transplant recipients at the center who were alive in 2010 and 2011 and had banked serum. The patients were receiving tacrolimus (Prograf)- and prednisolone-based immunosuppression.

Samples were tested by both polymerase chain reaction (PCR) for viral RNA – which was used to define infection – and serologic assays for antibodies to the virus. "We decided to screen all of our patients with PCR because we know serology outcomes differ greatly between the different tests used," Dr. van der Eijk explained.

Overall, 7 of the 263 patients studied were found to be infected with hepatitis E virus, for a point prevalence of 3%, and six of them had chronic infection (defined as PCR positivity for more than 6 months). The six men and one woman had a median age of 53 years. Retrospective serum testing showed that the time between transplantation and infection was a median of 8 years, but it ranged widely, from 1 to 20 years.

Viral genotyping showed that all of the patients were infected with genotype 3, which is associated with sporadic cases of hepatitis E in Western countries unrelated to travel and is likely of swine origin. Phylogenetic testing showed no evidence that the infections shared a common source or were acquired nosocomially.

Only two patients had virus-specific IgM antibodies at the time of initial PCR-detected infection and, on average, the PCR became positive 143 days before IgM antibodies were detectable. Thus, "PCR is superior [to serology] to detect infection in immunocompromised patients," Dr. van der Eijk commented.

The patients with chronic infection had elevations to varying extents of alanine aminotransferase levels, gamma-glutamyl transferase levels, or both. On liver biopsy, their Histologic Activity Index scores also ranged considerably, but three patients had scores of 10, indicating moderate disease, with features such as hepatocyte degeneration and fibrosis.

Although all of the patients with chronic hepatitis E had fecal shedding of the virus, none of their spouses was found to be infected on either serologic or PCR testing.

Dr. van der Eijk and Dr. Liang reported that they had no relevant conflicts of interest.

SAN FRANCISCO – Hepatitis E is an uncommon but often serious infection in immunosuppressed heart transplant recipients that warrants routine screening, according to investigators at Erasmus University Medical Center in Rotterdam, the Netherlands.

In a study of 263 recipients, 3% were found to have become infected with hepatitis E, most with symptomatic chronic disease. The infections ranged in severity from mild, transient viremia to severe and possibly progressive hepatitis with marked steatosis on liver biopsy.

"Chronic hepatitis E virus infection can have serious consequences in this group of patients," Dr. Annemiek A. van der Eijk said in presenting the findings at the annual meeting of the American Association for the Study of Liver Diseases (AASLD). "We advise systematic hepatitis E virus RNA screening in solid organ transplant recipients. In cases in which liver enzymes are increased, additional hepatitis E virus screening should be implemented."

"Chronic hepatitis E virus infection ... is a treatable disease," she added. Some patients were able to clear the virus when their immunosuppressants were tapered, but doing so also sometimes triggered rejection, which necessitated a resumption of therapy. "In our center, we are now treating patients with ribavirin (Copegus, Rebetol), but there are no large, randomized, controlled trials about the dose and duration of therapy."

"We advise systematic hepatitis E virus RNA screening in solid organ transplant recipients."

Importantly, she stressed, physicians should include hepatitis E infection in the differential diagnosis when transplant recipients have signs and symptoms of liver dysfunction, as it could be mistaken for a variety of other conditions having distinctly different treatments.

Chronicity "is not something we often associate with hepatitis E; it really doesn’t cause chronic infection like hepatitis B or C. But in this kind of immunosuppressed situation, it could," commented Dr. T. Jake Liang, president of the AASLD and chief of the Liver Diseases Branch at the National Institute of Diabetes and Digestive and Kidney Diseases.

"This [study] makes us aware of another cause of chronic liver disease, especially in people who are immunosuppressed, or receiving chemotherapy, or undergoing transplantation with lifelong immunosuppression," he said in a press conference.

Hepatitis E is transmitted mainly by the fecal-oral route (especially through contaminated water) but it can also be acquired by consuming raw or undercooked meat, through parenteral and vertical transmission, and – rarely – by person-to-person contact.

Swine are known to carry the virus. "In the Netherlands, more than 50% of the pig population is infected with hepatitis E virus, and 7% of the livers sold in supermarkets are hepatitis E virus RNA positive," Dr. van der Eijk noted.

Infection is especially worrisome in immunocompromised patients, as they can develop persistent elevation of liver enzymes and chronic hepatitis, with some reports also suggesting the possibility of rapid progression to cirrhosis.

In a cross-sectional study, the investigators tested serum samples from orthotopic heart transplant recipients at the center who were alive in 2010 and 2011 and had banked serum. The patients were receiving tacrolimus (Prograf)- and prednisolone-based immunosuppression.

Samples were tested by both polymerase chain reaction (PCR) for viral RNA – which was used to define infection – and serologic assays for antibodies to the virus. "We decided to screen all of our patients with PCR because we know serology outcomes differ greatly between the different tests used," Dr. van der Eijk explained.

Overall, 7 of the 263 patients studied were found to be infected with hepatitis E virus, for a point prevalence of 3%, and six of them had chronic infection (defined as PCR positivity for more than 6 months). The six men and one woman had a median age of 53 years. Retrospective serum testing showed that the time between transplantation and infection was a median of 8 years, but it ranged widely, from 1 to 20 years.

Viral genotyping showed that all of the patients were infected with genotype 3, which is associated with sporadic cases of hepatitis E in Western countries unrelated to travel and is likely of swine origin. Phylogenetic testing showed no evidence that the infections shared a common source or were acquired nosocomially.

Only two patients had virus-specific IgM antibodies at the time of initial PCR-detected infection and, on average, the PCR became positive 143 days before IgM antibodies were detectable. Thus, "PCR is superior [to serology] to detect infection in immunocompromised patients," Dr. van der Eijk commented.

The patients with chronic infection had elevations to varying extents of alanine aminotransferase levels, gamma-glutamyl transferase levels, or both. On liver biopsy, their Histologic Activity Index scores also ranged considerably, but three patients had scores of 10, indicating moderate disease, with features such as hepatocyte degeneration and fibrosis.

Although all of the patients with chronic hepatitis E had fecal shedding of the virus, none of their spouses was found to be infected on either serologic or PCR testing.

Dr. van der Eijk and Dr. Liang reported that they had no relevant conflicts of interest.

New-onset atrial fibrillation, or NOAF, occurred in nearly a third of 138 patients who underwent transcatheter aortic valve implantation in a prospective study, and the condition was associated with a significantly higher rate of cardioembolic events at 30-day and 12-month follow-up.

NOAF occurred in 44 patients at a median of 48 hours after transcatheter aortic valve implantation (TAVI), with 10 episodes resolving spontaneously within 12 hours, and 34 episodes requiring pharmacologic intervention. The rate of the combined end point of stroke and systemic embolism was 13.6% at 30 days in the NOAF group, compared with 3.2% in those who did not experience NOAF (odds ratio, 4.79); the rate was 15.9% vs. 3.2% at 12 months (OR, 5.0), Dr. Ignacio J. Amat-Santos of Laval University, Quebec City, and his colleagues reported online on Dec. 14 the Journal of the American College of Cardiology.

Courtesy Edwards Lifesciences

Significant independent predictors of NOAF included left atrial size (OR of 1.21/each increase of 1 mm/m2) and use of the transapical approach (OR, 4.08). An atrial size of 27 mm/m2 or greater as measured by echocardiography was identified as the cutoff point with the best sensitivity and specificity for predicting NOAF within 30 days of TAVI, the investigators said (J. Am. Coll. Cardiol. 2011 [doi:10/1016/j.jacc.2011.09.061]).

Furthermore, the incidence of NOAF in those with an atrial size of 27 mm/m² or greater undergoing TAVI by the transapical approach vs. the transfemoral approach was 57% vs. 12%, respectively, they noted.

Mortality, which was 16% and 21% in those with and without NOAF at 12 months, respectively, did not differ significantly between the groups at either follow-up, they noted.

Patients in the study had severe symptomatic aortic stenosis, but no history of chronic/paroxysmal atrial fibrillation. They underwent TAVI with a balloon-expandable valve by either the transapical or transfemoral approach, were enrolled consecutively between May 2007 and May 2011, and underwent continuous electrocardiographic monitoring during hospitalization. NOAF was defined as any episode of AF lasting longer than 30 seconds.

NOAF is a known complication in patients undergoing cardiovascular interventions, but this is one of the first studies to verify an increased risk of the condition in patients undergoing TAVI, which has emerged as an alternative treatment for patients with severe symptomatic aortic stenosis and high or prohibitive operative risk. The study is also among the first to characterize predictive factors for NOAF.

"The occurrence of cerebrovascular events is probably the most worrisome complication associated with TAVI, with an incidence of about 4%, one of the highest ever reported in the field of interventional cardiology," the investigators said, noting that the fact that more than 50% of the complications occur several days after TAVI suggests that "mechanisms other than those directly related to the procedure may be involved."

Indeed, the findings of this study suggest NOAF may be an important mechanism for late neurological events after TAVI, and if confirmed in larger studies, the findings may have implications for the development of prevention trials.

"Knowing the predictive factors of NOAF following TAVI should allow us to select the patients at higher risk for NOAF preventive studies in the setting of TAVI," they investigators said.

Also of note, some of the cardioembolic events in this study seemed to be related to the non-initiation of anticoagulant therapy, the investigators said, adding that the risk of a cardioembolic event was as high as 40% in those who had NOAF and who did not receive anticoagulant therapy.

This underscores the clinical relevance of optimizing antithrombotic treatment in this high-risk subset of patients, they concluded.

Dr. Amat-Santos disclosed that he received support from the Institute of Heart Sciences. Other authors disclosed having served as consultants for Edwards Lifesciences, and/or St. Jude Medical.

New-onset atrial fibrillation, or NOAF, occurred in nearly a third of 138 patients who underwent transcatheter aortic valve implantation in a prospective study, and the condition was associated with a significantly higher rate of cardioembolic events at 30-day and 12-month follow-up.

NOAF occurred in 44 patients at a median of 48 hours after transcatheter aortic valve implantation (TAVI), with 10 episodes resolving spontaneously within 12 hours, and 34 episodes requiring pharmacologic intervention. The rate of the combined end point of stroke and systemic embolism was 13.6% at 30 days in the NOAF group, compared with 3.2% in those who did not experience NOAF (odds ratio, 4.79); the rate was 15.9% vs. 3.2% at 12 months (OR, 5.0), Dr. Ignacio J. Amat-Santos of Laval University, Quebec City, and his colleagues reported online on Dec. 14 the Journal of the American College of Cardiology.

Courtesy Edwards Lifesciences

Significant independent predictors of NOAF included left atrial size (OR of 1.21/each increase of 1 mm/m2) and use of the transapical approach (OR, 4.08). An atrial size of 27 mm/m2 or greater as measured by echocardiography was identified as the cutoff point with the best sensitivity and specificity for predicting NOAF within 30 days of TAVI, the investigators said (J. Am. Coll. Cardiol. 2011 [doi:10/1016/j.jacc.2011.09.061]).

Furthermore, the incidence of NOAF in those with an atrial size of 27 mm/m² or greater undergoing TAVI by the transapical approach vs. the transfemoral approach was 57% vs. 12%, respectively, they noted.

Mortality, which was 16% and 21% in those with and without NOAF at 12 months, respectively, did not differ significantly between the groups at either follow-up, they noted.

Patients in the study had severe symptomatic aortic stenosis, but no history of chronic/paroxysmal atrial fibrillation. They underwent TAVI with a balloon-expandable valve by either the transapical or transfemoral approach, were enrolled consecutively between May 2007 and May 2011, and underwent continuous electrocardiographic monitoring during hospitalization. NOAF was defined as any episode of AF lasting longer than 30 seconds.

NOAF is a known complication in patients undergoing cardiovascular interventions, but this is one of the first studies to verify an increased risk of the condition in patients undergoing TAVI, which has emerged as an alternative treatment for patients with severe symptomatic aortic stenosis and high or prohibitive operative risk. The study is also among the first to characterize predictive factors for NOAF.

"The occurrence of cerebrovascular events is probably the most worrisome complication associated with TAVI, with an incidence of about 4%, one of the highest ever reported in the field of interventional cardiology," the investigators said, noting that the fact that more than 50% of the complications occur several days after TAVI suggests that "mechanisms other than those directly related to the procedure may be involved."

Indeed, the findings of this study suggest NOAF may be an important mechanism for late neurological events after TAVI, and if confirmed in larger studies, the findings may have implications for the development of prevention trials.

"Knowing the predictive factors of NOAF following TAVI should allow us to select the patients at higher risk for NOAF preventive studies in the setting of TAVI," they investigators said.

Also of note, some of the cardioembolic events in this study seemed to be related to the non-initiation of anticoagulant therapy, the investigators said, adding that the risk of a cardioembolic event was as high as 40% in those who had NOAF and who did not receive anticoagulant therapy.

This underscores the clinical relevance of optimizing antithrombotic treatment in this high-risk subset of patients, they concluded.

Dr. Amat-Santos disclosed that he received support from the Institute of Heart Sciences. Other authors disclosed having served as consultants for Edwards Lifesciences, and/or St. Jude Medical.

New-onset atrial fibrillation, or NOAF, occurred in nearly a third of 138 patients who underwent transcatheter aortic valve implantation in a prospective study, and the condition was associated with a significantly higher rate of cardioembolic events at 30-day and 12-month follow-up.

NOAF occurred in 44 patients at a median of 48 hours after transcatheter aortic valve implantation (TAVI), with 10 episodes resolving spontaneously within 12 hours, and 34 episodes requiring pharmacologic intervention. The rate of the combined end point of stroke and systemic embolism was 13.6% at 30 days in the NOAF group, compared with 3.2% in those who did not experience NOAF (odds ratio, 4.79); the rate was 15.9% vs. 3.2% at 12 months (OR, 5.0), Dr. Ignacio J. Amat-Santos of Laval University, Quebec City, and his colleagues reported online on Dec. 14 the Journal of the American College of Cardiology.

Courtesy Edwards Lifesciences

Significant independent predictors of NOAF included left atrial size (OR of 1.21/each increase of 1 mm/m2) and use of the transapical approach (OR, 4.08). An atrial size of 27 mm/m2 or greater as measured by echocardiography was identified as the cutoff point with the best sensitivity and specificity for predicting NOAF within 30 days of TAVI, the investigators said (J. Am. Coll. Cardiol. 2011 [doi:10/1016/j.jacc.2011.09.061]).

Furthermore, the incidence of NOAF in those with an atrial size of 27 mm/m² or greater undergoing TAVI by the transapical approach vs. the transfemoral approach was 57% vs. 12%, respectively, they noted.

Mortality, which was 16% and 21% in those with and without NOAF at 12 months, respectively, did not differ significantly between the groups at either follow-up, they noted.

Patients in the study had severe symptomatic aortic stenosis, but no history of chronic/paroxysmal atrial fibrillation. They underwent TAVI with a balloon-expandable valve by either the transapical or transfemoral approach, were enrolled consecutively between May 2007 and May 2011, and underwent continuous electrocardiographic monitoring during hospitalization. NOAF was defined as any episode of AF lasting longer than 30 seconds.

NOAF is a known complication in patients undergoing cardiovascular interventions, but this is one of the first studies to verify an increased risk of the condition in patients undergoing TAVI, which has emerged as an alternative treatment for patients with severe symptomatic aortic stenosis and high or prohibitive operative risk. The study is also among the first to characterize predictive factors for NOAF.

"The occurrence of cerebrovascular events is probably the most worrisome complication associated with TAVI, with an incidence of about 4%, one of the highest ever reported in the field of interventional cardiology," the investigators said, noting that the fact that more than 50% of the complications occur several days after TAVI suggests that "mechanisms other than those directly related to the procedure may be involved."

Indeed, the findings of this study suggest NOAF may be an important mechanism for late neurological events after TAVI, and if confirmed in larger studies, the findings may have implications for the development of prevention trials.

"Knowing the predictive factors of NOAF following TAVI should allow us to select the patients at higher risk for NOAF preventive studies in the setting of TAVI," they investigators said.

Also of note, some of the cardioembolic events in this study seemed to be related to the non-initiation of anticoagulant therapy, the investigators said, adding that the risk of a cardioembolic event was as high as 40% in those who had NOAF and who did not receive anticoagulant therapy.

This underscores the clinical relevance of optimizing antithrombotic treatment in this high-risk subset of patients, they concluded.

Dr. Amat-Santos disclosed that he received support from the Institute of Heart Sciences. Other authors disclosed having served as consultants for Edwards Lifesciences, and/or St. Jude Medical.

SAN FRANCISCO – Awareness of four factors that predict increased risk for hospital readmission after coronary artery bypass grafting may improve physicians’ ability to reduce early readmission rates among patients undergoing the procedure.

The four factors that independently predicted increased risk for hospital readmission after CABG in a study of 818 patients were preoperative congestive heart failure, chronic lung disease, a body mass index of 40 kg/m² or greater, and longer time spent on cardiopulmonary bypass, Dr. Kelly B. Currie said at the annual clinical congress of the American College of Surgeons.

Medicare payments to hospitals with high readmission rates will be reduced starting in October 2012 under provisions of the Patient Protection and Affordable Care Act. Payments will change from a fee-for-service model to a value-based model.

Readmission rates within 30 days of CABG range from 6% to 21% in the medical literature. In the third quarter of 2010, 10% of patients in the Society of Thoracic Surgeons (STS) database who underwent CABG were readmitted within 30 days, said Dr. Currie, a surgery resident at Bassett Medical Center, Cooperstown, N.Y.

She and her associates analyzed data from 460 patients undergoing CABG at their center from 2003 to 2010 and from 358 patients in the STS Heartsource database. Once they identified independent predictors of readmission, they conducted a second logistic regression analysis on the 358 patients in the STS database and created a "probability calculator" of readmission risk.

Congestive heart failure was associated with a 77% increase in risk for early readmission after CABG, and chronic lung disease was associated with an 82% increase in risk. The risk of readmission increased significantly by 0.6% with longer perfusion time, and increased nearly fourfold in obese patients with a body mass index of 40 or greater compared with normal-weight patients.

The risk for readmission decreased significantly by 40% in patients who underwent endoscopic vein harvest, she added.

Physicians may want to focus resources on the high-risk patients to decrease readmissions, Dr. Curry said. Readmissions might be lessened by instituting follow-up calls within a day of discharge, and/or having patients see their primary care physicians within 7 days of discharge. Efforts to improve verbal handoffs of patient care between inpatient nurses and visiting nurses, as well as the use of telemedicine, might be other effective ways to help avoid readmissions, she suggested.

"These are things we are going to be implementing in the near future, hopefully," she said.

The readmission risk calculator developed in this study probably cannot be applied to a broad population of patients because some of the variables are specific to the cardiac surgery population, she noted. The study’s techniques could be applied, however, to develop risk calculators for other populations.

Dr. Currie is collaborating with researchers at Columbia University in New York to develop an improved calculator by studying data on an expected 1,400 adult cardiac surgery cases at nine hospitals in five states.

Dr. Currie said she has no relevant conflicts of interest.

SAN FRANCISCO – Awareness of four factors that predict increased risk for hospital readmission after coronary artery bypass grafting may improve physicians’ ability to reduce early readmission rates among patients undergoing the procedure.

The four factors that independently predicted increased risk for hospital readmission after CABG in a study of 818 patients were preoperative congestive heart failure, chronic lung disease, a body mass index of 40 kg/m² or greater, and longer time spent on cardiopulmonary bypass, Dr. Kelly B. Currie said at the annual clinical congress of the American College of Surgeons.

Medicare payments to hospitals with high readmission rates will be reduced starting in October 2012 under provisions of the Patient Protection and Affordable Care Act. Payments will change from a fee-for-service model to a value-based model.

Readmission rates within 30 days of CABG range from 6% to 21% in the medical literature. In the third quarter of 2010, 10% of patients in the Society of Thoracic Surgeons (STS) database who underwent CABG were readmitted within 30 days, said Dr. Currie, a surgery resident at Bassett Medical Center, Cooperstown, N.Y.

She and her associates analyzed data from 460 patients undergoing CABG at their center from 2003 to 2010 and from 358 patients in the STS Heartsource database. Once they identified independent predictors of readmission, they conducted a second logistic regression analysis on the 358 patients in the STS database and created a "probability calculator" of readmission risk.

Congestive heart failure was associated with a 77% increase in risk for early readmission after CABG, and chronic lung disease was associated with an 82% increase in risk. The risk of readmission increased significantly by 0.6% with longer perfusion time, and increased nearly fourfold in obese patients with a body mass index of 40 or greater compared with normal-weight patients.

The risk for readmission decreased significantly by 40% in patients who underwent endoscopic vein harvest, she added.

Physicians may want to focus resources on the high-risk patients to decrease readmissions, Dr. Curry said. Readmissions might be lessened by instituting follow-up calls within a day of discharge, and/or having patients see their primary care physicians within 7 days of discharge. Efforts to improve verbal handoffs of patient care between inpatient nurses and visiting nurses, as well as the use of telemedicine, might be other effective ways to help avoid readmissions, she suggested.

"These are things we are going to be implementing in the near future, hopefully," she said.

The readmission risk calculator developed in this study probably cannot be applied to a broad population of patients because some of the variables are specific to the cardiac surgery population, she noted. The study’s techniques could be applied, however, to develop risk calculators for other populations.

Dr. Currie is collaborating with researchers at Columbia University in New York to develop an improved calculator by studying data on an expected 1,400 adult cardiac surgery cases at nine hospitals in five states.

Dr. Currie said she has no relevant conflicts of interest.

SAN FRANCISCO – Awareness of four factors that predict increased risk for hospital readmission after coronary artery bypass grafting may improve physicians’ ability to reduce early readmission rates among patients undergoing the procedure.

The four factors that independently predicted increased risk for hospital readmission after CABG in a study of 818 patients were preoperative congestive heart failure, chronic lung disease, a body mass index of 40 kg/m² or greater, and longer time spent on cardiopulmonary bypass, Dr. Kelly B. Currie said at the annual clinical congress of the American College of Surgeons.

Medicare payments to hospitals with high readmission rates will be reduced starting in October 2012 under provisions of the Patient Protection and Affordable Care Act. Payments will change from a fee-for-service model to a value-based model.

Readmission rates within 30 days of CABG range from 6% to 21% in the medical literature. In the third quarter of 2010, 10% of patients in the Society of Thoracic Surgeons (STS) database who underwent CABG were readmitted within 30 days, said Dr. Currie, a surgery resident at Bassett Medical Center, Cooperstown, N.Y.

She and her associates analyzed data from 460 patients undergoing CABG at their center from 2003 to 2010 and from 358 patients in the STS Heartsource database. Once they identified independent predictors of readmission, they conducted a second logistic regression analysis on the 358 patients in the STS database and created a "probability calculator" of readmission risk.

Congestive heart failure was associated with a 77% increase in risk for early readmission after CABG, and chronic lung disease was associated with an 82% increase in risk. The risk of readmission increased significantly by 0.6% with longer perfusion time, and increased nearly fourfold in obese patients with a body mass index of 40 or greater compared with normal-weight patients.

The risk for readmission decreased significantly by 40% in patients who underwent endoscopic vein harvest, she added.

Physicians may want to focus resources on the high-risk patients to decrease readmissions, Dr. Curry said. Readmissions might be lessened by instituting follow-up calls within a day of discharge, and/or having patients see their primary care physicians within 7 days of discharge. Efforts to improve verbal handoffs of patient care between inpatient nurses and visiting nurses, as well as the use of telemedicine, might be other effective ways to help avoid readmissions, she suggested.

"These are things we are going to be implementing in the near future, hopefully," she said.

The readmission risk calculator developed in this study probably cannot be applied to a broad population of patients because some of the variables are specific to the cardiac surgery population, she noted. The study’s techniques could be applied, however, to develop risk calculators for other populations.

Dr. Currie is collaborating with researchers at Columbia University in New York to develop an improved calculator by studying data on an expected 1,400 adult cardiac surgery cases at nine hospitals in five states.

Dr. Currie said she has no relevant conflicts of interest.

BOSTON – Just 1% of all surgical procedures are associated with complex surgical site infections, but many develop in association with ill-suited prophylactic antibiotic regimens, according to an analysis of more than 2.4 million American who underwent cardiac or orthopedic surgery during 2006-2009.

Nevertheless, "the vast majority [of surgery patients] don’t get SSIs. Do we want to modify treatment for all patients to address the small proportion who get complex SSIs?" asked Dr. Dale W. Bratzler.

The low overall rate of complex SSIs suggests that any changes to standard SSI prophylaxis regimens should proceed cautiously. "What we need most are strategies for identifying patients at high risk for SSI due to drug-resistant organisms for targeting modified antimicrobial prophylaxis regimens," said Dr. Bratzler, a professor in the department of health administration and policy of the University of Oklahoma, Oklahoma City.

The analysis he reported at the annual meeting of the Infectious Diseases Society of America used data from two large U.S. databases collected from January 2006 to December 2009. Information on the pathogen distribution of SSIs came from the National Healthcare Safety Network database of the Centers for Disease Control and Prevention, which included data from 1,389 U.S. hospitals during this period on the number and type of SSIs that occurred in patients who underwent coronary artery bypass grafting (CABG), and those who had primary total hip or total knee replacement surgery. The second database, from the Hospital Inpatient Quality Reporting Program of the Centers for Medicare and Medicaid Services, collected data on the type of antimicrobial prophylaxis received by patients who underwent these surgical procedures at 3,330 U.S. hospitals.

"Do we want to modify treatment for all patients to address the small proportion who get complex SSIs?"

The National Healthcare Safety Network data showed that a total of 3,024 patients developed a complex SSI among the 207,053 who underwent CABG (1.5%), and 3,532 patients had a complex SSI among the 495,529 patients who had primary hip or knee replacement surgery (0.7%), Dr. Bratzler reported. Complex SSIs were defined as either deep incisional infections, or infections of an organ or surgical space. Among the CABG-associated complex SSIs, 34% were caused by gram-negative bacteria, with the balance caused by gram-positive pathogens, and 17% of all SSIs involved methicillin-resistant Staphylococcus aureus (MRSA). In the arthroplasty patients, 18% of the complex SSIs involved a gram-negative pathogen, and 21% of all infections had MRSA involvement.

The data on type of antibiotic prophylaxis used showed that among 428,541 patients who underwent CABG in this dataset, 67% received "standard" prophylaxis with either cefazolin or cefuroxime; 12% received a regimen designed for patients with beta-lactam allergy with either vancomycin or clindamycin, plus an aminoglycoside added at the provider’s discretion; and 15% had prophylaxis with an extended-spectrum regimen consisting of either vancomycin plus cefazolin or cefuroxime, or an aminoglycoside plus cefazolin or cefuroxime. The remaining 6% of patients received another prophylaxis regimen.

The prophylaxis data for 2,007,162 arthroplasty patients showed that the standard regimen was used in 77%, the beta-lactam allergy regimen in 13%, and the extended-spectrum regimen in 7%, with the remaining 3% of patients receiving something else.

Dr. Bratzler then compared the expected efficacy of the three most commonly used regimens against the pattern of SSIs that actually occurred in these patients. Patients who received the standard regimen could expect protection against about 40% of the types of bacteria that actually wound up producing SSIs. Patients who received the beta-lactam allergy regimens could expect protection against 56%-96% of the pathogens that actually caused the SSIs, and patients who received the extended-spectrum regimens could expect protection against 69%-96%, he said.

The researchers could not do a more detailed analysis of the relationship between the type of prophylaxis used and the pattern of SSIs that subsequently developed because both databases were anonymous, which precluded cross-referencing the information.

Dr. Bratzler said that he had no disclosures.

BOSTON – Just 1% of all surgical procedures are associated with complex surgical site infections, but many develop in association with ill-suited prophylactic antibiotic regimens, according to an analysis of more than 2.4 million American who underwent cardiac or orthopedic surgery during 2006-2009.

Nevertheless, "the vast majority [of surgery patients] don’t get SSIs. Do we want to modify treatment for all patients to address the small proportion who get complex SSIs?" asked Dr. Dale W. Bratzler.

The low overall rate of complex SSIs suggests that any changes to standard SSI prophylaxis regimens should proceed cautiously. "What we need most are strategies for identifying patients at high risk for SSI due to drug-resistant organisms for targeting modified antimicrobial prophylaxis regimens," said Dr. Bratzler, a professor in the department of health administration and policy of the University of Oklahoma, Oklahoma City.

The analysis he reported at the annual meeting of the Infectious Diseases Society of America used data from two large U.S. databases collected from January 2006 to December 2009. Information on the pathogen distribution of SSIs came from the National Healthcare Safety Network database of the Centers for Disease Control and Prevention, which included data from 1,389 U.S. hospitals during this period on the number and type of SSIs that occurred in patients who underwent coronary artery bypass grafting (CABG), and those who had primary total hip or total knee replacement surgery. The second database, from the Hospital Inpatient Quality Reporting Program of the Centers for Medicare and Medicaid Services, collected data on the type of antimicrobial prophylaxis received by patients who underwent these surgical procedures at 3,330 U.S. hospitals.

"Do we want to modify treatment for all patients to address the small proportion who get complex SSIs?"

The National Healthcare Safety Network data showed that a total of 3,024 patients developed a complex SSI among the 207,053 who underwent CABG (1.5%), and 3,532 patients had a complex SSI among the 495,529 patients who had primary hip or knee replacement surgery (0.7%), Dr. Bratzler reported. Complex SSIs were defined as either deep incisional infections, or infections of an organ or surgical space. Among the CABG-associated complex SSIs, 34% were caused by gram-negative bacteria, with the balance caused by gram-positive pathogens, and 17% of all SSIs involved methicillin-resistant Staphylococcus aureus (MRSA). In the arthroplasty patients, 18% of the complex SSIs involved a gram-negative pathogen, and 21% of all infections had MRSA involvement.

The data on type of antibiotic prophylaxis used showed that among 428,541 patients who underwent CABG in this dataset, 67% received "standard" prophylaxis with either cefazolin or cefuroxime; 12% received a regimen designed for patients with beta-lactam allergy with either vancomycin or clindamycin, plus an aminoglycoside added at the provider’s discretion; and 15% had prophylaxis with an extended-spectrum regimen consisting of either vancomycin plus cefazolin or cefuroxime, or an aminoglycoside plus cefazolin or cefuroxime. The remaining 6% of patients received another prophylaxis regimen.

The prophylaxis data for 2,007,162 arthroplasty patients showed that the standard regimen was used in 77%, the beta-lactam allergy regimen in 13%, and the extended-spectrum regimen in 7%, with the remaining 3% of patients receiving something else.

Dr. Bratzler then compared the expected efficacy of the three most commonly used regimens against the pattern of SSIs that actually occurred in these patients. Patients who received the standard regimen could expect protection against about 40% of the types of bacteria that actually wound up producing SSIs. Patients who received the beta-lactam allergy regimens could expect protection against 56%-96% of the pathogens that actually caused the SSIs, and patients who received the extended-spectrum regimens could expect protection against 69%-96%, he said.

The researchers could not do a more detailed analysis of the relationship between the type of prophylaxis used and the pattern of SSIs that subsequently developed because both databases were anonymous, which precluded cross-referencing the information.

Dr. Bratzler said that he had no disclosures.

BOSTON – Just 1% of all surgical procedures are associated with complex surgical site infections, but many develop in association with ill-suited prophylactic antibiotic regimens, according to an analysis of more than 2.4 million American who underwent cardiac or orthopedic surgery during 2006-2009.

Nevertheless, "the vast majority [of surgery patients] don’t get SSIs. Do we want to modify treatment for all patients to address the small proportion who get complex SSIs?" asked Dr. Dale W. Bratzler.

The low overall rate of complex SSIs suggests that any changes to standard SSI prophylaxis regimens should proceed cautiously. "What we need most are strategies for identifying patients at high risk for SSI due to drug-resistant organisms for targeting modified antimicrobial prophylaxis regimens," said Dr. Bratzler, a professor in the department of health administration and policy of the University of Oklahoma, Oklahoma City.

The analysis he reported at the annual meeting of the Infectious Diseases Society of America used data from two large U.S. databases collected from January 2006 to December 2009. Information on the pathogen distribution of SSIs came from the National Healthcare Safety Network database of the Centers for Disease Control and Prevention, which included data from 1,389 U.S. hospitals during this period on the number and type of SSIs that occurred in patients who underwent coronary artery bypass grafting (CABG), and those who had primary total hip or total knee replacement surgery. The second database, from the Hospital Inpatient Quality Reporting Program of the Centers for Medicare and Medicaid Services, collected data on the type of antimicrobial prophylaxis received by patients who underwent these surgical procedures at 3,330 U.S. hospitals.

"Do we want to modify treatment for all patients to address the small proportion who get complex SSIs?"

The National Healthcare Safety Network data showed that a total of 3,024 patients developed a complex SSI among the 207,053 who underwent CABG (1.5%), and 3,532 patients had a complex SSI among the 495,529 patients who had primary hip or knee replacement surgery (0.7%), Dr. Bratzler reported. Complex SSIs were defined as either deep incisional infections, or infections of an organ or surgical space. Among the CABG-associated complex SSIs, 34% were caused by gram-negative bacteria, with the balance caused by gram-positive pathogens, and 17% of all SSIs involved methicillin-resistant Staphylococcus aureus (MRSA). In the arthroplasty patients, 18% of the complex SSIs involved a gram-negative pathogen, and 21% of all infections had MRSA involvement.

The data on type of antibiotic prophylaxis used showed that among 428,541 patients who underwent CABG in this dataset, 67% received "standard" prophylaxis with either cefazolin or cefuroxime; 12% received a regimen designed for patients with beta-lactam allergy with either vancomycin or clindamycin, plus an aminoglycoside added at the provider’s discretion; and 15% had prophylaxis with an extended-spectrum regimen consisting of either vancomycin plus cefazolin or cefuroxime, or an aminoglycoside plus cefazolin or cefuroxime. The remaining 6% of patients received another prophylaxis regimen.

The prophylaxis data for 2,007,162 arthroplasty patients showed that the standard regimen was used in 77%, the beta-lactam allergy regimen in 13%, and the extended-spectrum regimen in 7%, with the remaining 3% of patients receiving something else.

Dr. Bratzler then compared the expected efficacy of the three most commonly used regimens against the pattern of SSIs that actually occurred in these patients. Patients who received the standard regimen could expect protection against about 40% of the types of bacteria that actually wound up producing SSIs. Patients who received the beta-lactam allergy regimens could expect protection against 56%-96% of the pathogens that actually caused the SSIs, and patients who received the extended-spectrum regimens could expect protection against 69%-96%, he said.

The researchers could not do a more detailed analysis of the relationship between the type of prophylaxis used and the pattern of SSIs that subsequently developed because both databases were anonymous, which precluded cross-referencing the information.

Dr. Bratzler said that he had no disclosures.

COLORADO SPRINGS – Physicians at Emory University Hospital now have a firmer grip on what they’re dealing with in reducing 30-day readmissions.

The knowledge that there are three major risk factors – preoperative failure to thrive, an initial length of stay greater than 10 days, and Hispanic ethnicity – for readmission following pediatric congenital heart disease surgery is a tool for improvement, said Dr. Brian E. Kogon of Emory University, Atlanta.

"These data are obviously our data and are very specific to our hospital, our location, and our patient population. I would think that it’s going to be very different throughout the country based on whether you’re at an academic center or private center, urban versus rural setting, and even in adult cardiac, general thoracic, and pediatric practices," Dr. Kogon said in presenting the study findings at the annual meeting of the Western Thoracic Surgical Association.

The important thing is for physicians and surgeons to analyze their own hospital’s readmission experience, identify the risk factors, and then address the potentially modifiable ones in an effort to drive that readmission rate down, added Dr. Kogon, director of the congenital cardiac surgery fellowship program at Emory.

Studying Readmissions Following Pediatric Surgery

Readmissions within 30 days are increasingly viewed by third-party payers as preventable complications warranting stiff payment penalties. The focus thus far has been on the adult world, but at some point pediatric care will come under scrutiny as well. This realization led Dr. Kogon and his coworkers to analyze their institutional experience via a retrospective cohort study.

During 2002-2009, the annual 30-day readmission rates following pediatric surgery for congenital heart disease were 5.9%-10.4%, with a median of 8.7%. Those rates are relatively low; other centers typically report readmission rates of 10%-20%, he noted.

In 2009, 685 patients were discharged after pediatric congenital heart disease surgery; 70 of them had 74 readmissions. Among the key findings: only 15% of readmissions were for cardiac reasons. Indeed, the top three reasons for readmission were pleural or pericardial effusions, accounting for 26% of all readmissions; gastrointestinal problems, 24%; and infection, 19%.

Readmissions were costly. A total of 69% of patients were readmitted to a ward, 31% to the ICU. Upon readmission these patients spent a total of 653 additional days – almost 22 months – in the hospital.

The investigators scrutinized numerous potential demographic, preoperative, operative, and postoperative risk factors for readmission. Only three proved significant in a multivariate analysis: an initial length of stay greater than 10 days was associated with a 4.4-fold increased risk of readmission; a preoperative diagnosis of failure to thrive was associated with a 2.7-fold risk; and Hispanic ethnicity was associated with a 1.87-fold increased risk.

These readmissions occurred despite an intense discharge process and close follow-up. All families at the pediatric heart surgery unit attend a discharge class and a CPR training class. A pharmacist is on hand at the discharge class to review medications. Shunt recipients and newborns receive additional education. All case-management issues, such as formula supplies and home health equipment, are resolved before discharge. Patients meet with a cardiothoracic surgeon during their first week out of hospital, a cardiologist the second week, and thereafter with their primary care provider.

The median time to the first scheduled outpatient appointment was 4.5 days postdischarge. The median time to readmission was 8 days. Thirty-one percent of patients were readmitted prior to their first clinic appointment, 10% directly from the clinic, and 50% after their first clinic visit. The rest were readmitted after being no-shows for their clinic visit.

Dr. Kogon said he suspects that Hispanics were at increased risk for readmission because of educational and language barriers. Although a Spanish-language interpreter is present at the discharge class as needed, Dr. Kogon and his colleagues have observed that many Hispanic families nonetheless return unclear about medication and feeding regimens.

"I think there’s still a gap in our education of those patients," he said.

Discussant Dr. David R. Clarke said it might be argued that if a hospital doesn’t have a certain number of readmissions, then patients are being kept in the hospital too long.

"On a practical level, how much do we spend during the initial admission to ensure no readmissions? Do we automatically keep patients identified as high risk, such as Hispanics, 2, 3, or 4 extra days to minimize their readmission rate? And even if we do that and other things, is it really possible to prevent readmissions?" wondered Dr. Clarke of Children’s Hospital Colorado, Denver.

Dr. Kogon replied that this is the key question his colleagues raised when he shared the study findings. The group has decided to modify the discharge process for their high-risk patients, keeping them in the hospital a day or so longer while continuing to collect data in order to see if this pays off in fewer readmissions.

Dr. Kogon declared having no financial conflicts.

COLORADO SPRINGS – Physicians at Emory University Hospital now have a firmer grip on what they’re dealing with in reducing 30-day readmissions.

The knowledge that there are three major risk factors – preoperative failure to thrive, an initial length of stay greater than 10 days, and Hispanic ethnicity – for readmission following pediatric congenital heart disease surgery is a tool for improvement, said Dr. Brian E. Kogon of Emory University, Atlanta.

"These data are obviously our data and are very specific to our hospital, our location, and our patient population. I would think that it’s going to be very different throughout the country based on whether you’re at an academic center or private center, urban versus rural setting, and even in adult cardiac, general thoracic, and pediatric practices," Dr. Kogon said in presenting the study findings at the annual meeting of the Western Thoracic Surgical Association.

The important thing is for physicians and surgeons to analyze their own hospital’s readmission experience, identify the risk factors, and then address the potentially modifiable ones in an effort to drive that readmission rate down, added Dr. Kogon, director of the congenital cardiac surgery fellowship program at Emory.

Studying Readmissions Following Pediatric Surgery

Readmissions within 30 days are increasingly viewed by third-party payers as preventable complications warranting stiff payment penalties. The focus thus far has been on the adult world, but at some point pediatric care will come under scrutiny as well. This realization led Dr. Kogon and his coworkers to analyze their institutional experience via a retrospective cohort study.

During 2002-2009, the annual 30-day readmission rates following pediatric surgery for congenital heart disease were 5.9%-10.4%, with a median of 8.7%. Those rates are relatively low; other centers typically report readmission rates of 10%-20%, he noted.

In 2009, 685 patients were discharged after pediatric congenital heart disease surgery; 70 of them had 74 readmissions. Among the key findings: only 15% of readmissions were for cardiac reasons. Indeed, the top three reasons for readmission were pleural or pericardial effusions, accounting for 26% of all readmissions; gastrointestinal problems, 24%; and infection, 19%.

Readmissions were costly. A total of 69% of patients were readmitted to a ward, 31% to the ICU. Upon readmission these patients spent a total of 653 additional days – almost 22 months – in the hospital.

The investigators scrutinized numerous potential demographic, preoperative, operative, and postoperative risk factors for readmission. Only three proved significant in a multivariate analysis: an initial length of stay greater than 10 days was associated with a 4.4-fold increased risk of readmission; a preoperative diagnosis of failure to thrive was associated with a 2.7-fold risk; and Hispanic ethnicity was associated with a 1.87-fold increased risk.

These readmissions occurred despite an intense discharge process and close follow-up. All families at the pediatric heart surgery unit attend a discharge class and a CPR training class. A pharmacist is on hand at the discharge class to review medications. Shunt recipients and newborns receive additional education. All case-management issues, such as formula supplies and home health equipment, are resolved before discharge. Patients meet with a cardiothoracic surgeon during their first week out of hospital, a cardiologist the second week, and thereafter with their primary care provider.

The median time to the first scheduled outpatient appointment was 4.5 days postdischarge. The median time to readmission was 8 days. Thirty-one percent of patients were readmitted prior to their first clinic appointment, 10% directly from the clinic, and 50% after their first clinic visit. The rest were readmitted after being no-shows for their clinic visit.

Dr. Kogon said he suspects that Hispanics were at increased risk for readmission because of educational and language barriers. Although a Spanish-language interpreter is present at the discharge class as needed, Dr. Kogon and his colleagues have observed that many Hispanic families nonetheless return unclear about medication and feeding regimens.

"I think there’s still a gap in our education of those patients," he said.

Discussant Dr. David R. Clarke said it might be argued that if a hospital doesn’t have a certain number of readmissions, then patients are being kept in the hospital too long.

"On a practical level, how much do we spend during the initial admission to ensure no readmissions? Do we automatically keep patients identified as high risk, such as Hispanics, 2, 3, or 4 extra days to minimize their readmission rate? And even if we do that and other things, is it really possible to prevent readmissions?" wondered Dr. Clarke of Children’s Hospital Colorado, Denver.

Dr. Kogon replied that this is the key question his colleagues raised when he shared the study findings. The group has decided to modify the discharge process for their high-risk patients, keeping them in the hospital a day or so longer while continuing to collect data in order to see if this pays off in fewer readmissions.

Dr. Kogon declared having no financial conflicts.

COLORADO SPRINGS – Physicians at Emory University Hospital now have a firmer grip on what they’re dealing with in reducing 30-day readmissions.

The knowledge that there are three major risk factors – preoperative failure to thrive, an initial length of stay greater than 10 days, and Hispanic ethnicity – for readmission following pediatric congenital heart disease surgery is a tool for improvement, said Dr. Brian E. Kogon of Emory University, Atlanta.

"These data are obviously our data and are very specific to our hospital, our location, and our patient population. I would think that it’s going to be very different throughout the country based on whether you’re at an academic center or private center, urban versus rural setting, and even in adult cardiac, general thoracic, and pediatric practices," Dr. Kogon said in presenting the study findings at the annual meeting of the Western Thoracic Surgical Association.

The important thing is for physicians and surgeons to analyze their own hospital’s readmission experience, identify the risk factors, and then address the potentially modifiable ones in an effort to drive that readmission rate down, added Dr. Kogon, director of the congenital cardiac surgery fellowship program at Emory.

Studying Readmissions Following Pediatric Surgery

Readmissions within 30 days are increasingly viewed by third-party payers as preventable complications warranting stiff payment penalties. The focus thus far has been on the adult world, but at some point pediatric care will come under scrutiny as well. This realization led Dr. Kogon and his coworkers to analyze their institutional experience via a retrospective cohort study.

During 2002-2009, the annual 30-day readmission rates following pediatric surgery for congenital heart disease were 5.9%-10.4%, with a median of 8.7%. Those rates are relatively low; other centers typically report readmission rates of 10%-20%, he noted.

In 2009, 685 patients were discharged after pediatric congenital heart disease surgery; 70 of them had 74 readmissions. Among the key findings: only 15% of readmissions were for cardiac reasons. Indeed, the top three reasons for readmission were pleural or pericardial effusions, accounting for 26% of all readmissions; gastrointestinal problems, 24%; and infection, 19%.

Readmissions were costly. A total of 69% of patients were readmitted to a ward, 31% to the ICU. Upon readmission these patients spent a total of 653 additional days – almost 22 months – in the hospital.

The investigators scrutinized numerous potential demographic, preoperative, operative, and postoperative risk factors for readmission. Only three proved significant in a multivariate analysis: an initial length of stay greater than 10 days was associated with a 4.4-fold increased risk of readmission; a preoperative diagnosis of failure to thrive was associated with a 2.7-fold risk; and Hispanic ethnicity was associated with a 1.87-fold increased risk.

These readmissions occurred despite an intense discharge process and close follow-up. All families at the pediatric heart surgery unit attend a discharge class and a CPR training class. A pharmacist is on hand at the discharge class to review medications. Shunt recipients and newborns receive additional education. All case-management issues, such as formula supplies and home health equipment, are resolved before discharge. Patients meet with a cardiothoracic surgeon during their first week out of hospital, a cardiologist the second week, and thereafter with their primary care provider.

The median time to the first scheduled outpatient appointment was 4.5 days postdischarge. The median time to readmission was 8 days. Thirty-one percent of patients were readmitted prior to their first clinic appointment, 10% directly from the clinic, and 50% after their first clinic visit. The rest were readmitted after being no-shows for their clinic visit.

Dr. Kogon said he suspects that Hispanics were at increased risk for readmission because of educational and language barriers. Although a Spanish-language interpreter is present at the discharge class as needed, Dr. Kogon and his colleagues have observed that many Hispanic families nonetheless return unclear about medication and feeding regimens.

"I think there’s still a gap in our education of those patients," he said.

Discussant Dr. David R. Clarke said it might be argued that if a hospital doesn’t have a certain number of readmissions, then patients are being kept in the hospital too long.

"On a practical level, how much do we spend during the initial admission to ensure no readmissions? Do we automatically keep patients identified as high risk, such as Hispanics, 2, 3, or 4 extra days to minimize their readmission rate? And even if we do that and other things, is it really possible to prevent readmissions?" wondered Dr. Clarke of Children’s Hospital Colorado, Denver.

Dr. Kogon replied that this is the key question his colleagues raised when he shared the study findings. The group has decided to modify the discharge process for their high-risk patients, keeping them in the hospital a day or so longer while continuing to collect data in order to see if this pays off in fewer readmissions.

Dr. Kogon declared having no financial conflicts.

SAN DIEGO – Heart transplant recipients who develop circulating antibodies to human tissues in the first year post transplantation are at heightened risk for poor outcomes and may therefore need closer monitoring, suggests a prospective observational study.

One in seven of the patients studied developed circulating antibodies that specifically targeted human leukocyte antigens on donor tissue, and one in three developed nonspecific antibodies, according to results reported at the annual meeting of the International Society for Heart and Lung Transplantation.

Relative to their counterparts who did not develop any antibodies, patients who developed either type were more likely to experience both antibody-mediated and cellular rejection. In addition, those developing the donor-specific type were more likely to experience cardiac allograft vasculopathy and to die.

"Patients with donor-specific antibodies or nonspecific antibodies may require more intensive monitoring and augmented immunosuppression to improve their long-term outcomes," commented lead investigator Dr. Jignesh Patel, co–medical director of the heart transplant program at the Cedars-Sinai Heart Institute in Los Angeles. "Further studies are needed to determine the optimum therapy for these patients."

He acknowledged that the issue is complicated, because some patients with donor-specific antibodies (DSA) never experienced rejection, yet others with nonspecific antibodies did. These outcomes suggest that the nature of the antibodies is key. As a result, it is tricky to manage patients who develop antibodies but don’t have any symptoms of rejection.

At his institution, Dr. Patel said, clinicians don’t step up the number of biopsies performed to monitor for rejection in heart transplant recipients who develop antibodies unless they become symptomatic. However, they are cautious about long-term management of immunosuppression. "We will think twice about weaning them off prednisone," he noted. "More likely, we are kind of tending to switch them to a proliferation signaling inhibitor earlier when we see donor-specific antibodies."

Dr. Patel and his coinvestigators studied 144 patients who underwent heart transplantation in 2003-2010 and had serial antibody monitoring by solid-phase assays at baseline (the time of transplantation) and at 1, 3, 6, 9, and 12 months, at minimum.

"More recently introduced methods using solid-phase matrices coated with HLA antigens have demonstrated the ability to detect and identify HLA antibodies with high sensitivity and accuracy," he said.

Because the study period preceded the guidelines that recommended antibody monitoring, these patients were being followed more closely than usual out of concern that they were at heightened risk for antibody development, he said.

On average, the patients had seven antibody measurements during their first year post transplantation.

Study results showed that in the first year after transplantation, 14% of patients developed DSA and 32% developed non–donor-specific antibodies (non-DSA), while the rest did not develop any.

The mean age (approximately 53 years) was similar across groups. Relative to those who did not develop any antibodies, patients who developed non-DSA were more likely to be female (54% vs. 22%). Also, ischemic time was shorter for patients who developed DSA (183 minutes) or non-DSA (195 minutes) than for their counterparts who did not develop any antibodies (230 minutes).

The three groups of patients were generally similar with respect to immunosuppressive therapy at baseline, including receipt of calcineurin inhibitors and antiproliferative agents.

But the group developing DSA was significantly less likely than the group not developing antibodies to be weaned off prednisone (7% vs. 46%), and both the DSA and non-DSA groups were more likely than their counterparts with no antibodies to have received induction therapy (45% and 39% vs. 15%).

The 1-year rate of freedom from antibody-mediated rejection was poorer for patients who developed DSA (65%) or non-DSA (76%), compared with their peers who developed no antibodies (94%). The findings were similar with respect to rates of freedom from acute cellular rejection (80% and 87% vs. 99%, respectively).

The temporal patterns did differ somewhat according to type of rejection, according to Dr. Patel.

"With regard to cellular rejection, it appeared that a lot of events in the patients who developed donor-specific antibodies occurred toward the end of the first year, in comparison to the patients who developed antibody-mediated rejection, where most of the events tended to occur early" post transplant, he observed.

Relative to their counterparts who did not develop antibodies, the patients who developed DSA also had significantly poorer 3-year rates of survival (65% vs. 85%) and freedom from cardiac allograft vasculopathy, which was defined as the development of vascular stenosis exceeding 30% (70% vs. 88%).

Dr. Patel reported that he had no conflicts of interest related to the study.

SAN DIEGO – Heart transplant recipients who develop circulating antibodies to human tissues in the first year post transplantation are at heightened risk for poor outcomes and may therefore need closer monitoring, suggests a prospective observational study.

One in seven of the patients studied developed circulating antibodies that specifically targeted human leukocyte antigens on donor tissue, and one in three developed nonspecific antibodies, according to results reported at the annual meeting of the International Society for Heart and Lung Transplantation.

Relative to their counterparts who did not develop any antibodies, patients who developed either type were more likely to experience both antibody-mediated and cellular rejection. In addition, those developing the donor-specific type were more likely to experience cardiac allograft vasculopathy and to die.

"Patients with donor-specific antibodies or nonspecific antibodies may require more intensive monitoring and augmented immunosuppression to improve their long-term outcomes," commented lead investigator Dr. Jignesh Patel, co–medical director of the heart transplant program at the Cedars-Sinai Heart Institute in Los Angeles. "Further studies are needed to determine the optimum therapy for these patients."

He acknowledged that the issue is complicated, because some patients with donor-specific antibodies (DSA) never experienced rejection, yet others with nonspecific antibodies did. These outcomes suggest that the nature of the antibodies is key. As a result, it is tricky to manage patients who develop antibodies but don’t have any symptoms of rejection.

At his institution, Dr. Patel said, clinicians don’t step up the number of biopsies performed to monitor for rejection in heart transplant recipients who develop antibodies unless they become symptomatic. However, they are cautious about long-term management of immunosuppression. "We will think twice about weaning them off prednisone," he noted. "More likely, we are kind of tending to switch them to a proliferation signaling inhibitor earlier when we see donor-specific antibodies."

Dr. Patel and his coinvestigators studied 144 patients who underwent heart transplantation in 2003-2010 and had serial antibody monitoring by solid-phase assays at baseline (the time of transplantation) and at 1, 3, 6, 9, and 12 months, at minimum.

"More recently introduced methods using solid-phase matrices coated with HLA antigens have demonstrated the ability to detect and identify HLA antibodies with high sensitivity and accuracy," he said.

Because the study period preceded the guidelines that recommended antibody monitoring, these patients were being followed more closely than usual out of concern that they were at heightened risk for antibody development, he said.

On average, the patients had seven antibody measurements during their first year post transplantation.

Study results showed that in the first year after transplantation, 14% of patients developed DSA and 32% developed non–donor-specific antibodies (non-DSA), while the rest did not develop any.

The mean age (approximately 53 years) was similar across groups. Relative to those who did not develop any antibodies, patients who developed non-DSA were more likely to be female (54% vs. 22%). Also, ischemic time was shorter for patients who developed DSA (183 minutes) or non-DSA (195 minutes) than for their counterparts who did not develop any antibodies (230 minutes).

The three groups of patients were generally similar with respect to immunosuppressive therapy at baseline, including receipt of calcineurin inhibitors and antiproliferative agents.

But the group developing DSA was significantly less likely than the group not developing antibodies to be weaned off prednisone (7% vs. 46%), and both the DSA and non-DSA groups were more likely than their counterparts with no antibodies to have received induction therapy (45% and 39% vs. 15%).

The 1-year rate of freedom from antibody-mediated rejection was poorer for patients who developed DSA (65%) or non-DSA (76%), compared with their peers who developed no antibodies (94%). The findings were similar with respect to rates of freedom from acute cellular rejection (80% and 87% vs. 99%, respectively).

The temporal patterns did differ somewhat according to type of rejection, according to Dr. Patel.

"With regard to cellular rejection, it appeared that a lot of events in the patients who developed donor-specific antibodies occurred toward the end of the first year, in comparison to the patients who developed antibody-mediated rejection, where most of the events tended to occur early" post transplant, he observed.

Relative to their counterparts who did not develop antibodies, the patients who developed DSA also had significantly poorer 3-year rates of survival (65% vs. 85%) and freedom from cardiac allograft vasculopathy, which was defined as the development of vascular stenosis exceeding 30% (70% vs. 88%).

Dr. Patel reported that he had no conflicts of interest related to the study.

SAN DIEGO – Heart transplant recipients who develop circulating antibodies to human tissues in the first year post transplantation are at heightened risk for poor outcomes and may therefore need closer monitoring, suggests a prospective observational study.

One in seven of the patients studied developed circulating antibodies that specifically targeted human leukocyte antigens on donor tissue, and one in three developed nonspecific antibodies, according to results reported at the annual meeting of the International Society for Heart and Lung Transplantation.

Relative to their counterparts who did not develop any antibodies, patients who developed either type were more likely to experience both antibody-mediated and cellular rejection. In addition, those developing the donor-specific type were more likely to experience cardiac allograft vasculopathy and to die.

"Patients with donor-specific antibodies or nonspecific antibodies may require more intensive monitoring and augmented immunosuppression to improve their long-term outcomes," commented lead investigator Dr. Jignesh Patel, co–medical director of the heart transplant program at the Cedars-Sinai Heart Institute in Los Angeles. "Further studies are needed to determine the optimum therapy for these patients."

He acknowledged that the issue is complicated, because some patients with donor-specific antibodies (DSA) never experienced rejection, yet others with nonspecific antibodies did. These outcomes suggest that the nature of the antibodies is key. As a result, it is tricky to manage patients who develop antibodies but don’t have any symptoms of rejection.

At his institution, Dr. Patel said, clinicians don’t step up the number of biopsies performed to monitor for rejection in heart transplant recipients who develop antibodies unless they become symptomatic. However, they are cautious about long-term management of immunosuppression. "We will think twice about weaning them off prednisone," he noted. "More likely, we are kind of tending to switch them to a proliferation signaling inhibitor earlier when we see donor-specific antibodies."

Dr. Patel and his coinvestigators studied 144 patients who underwent heart transplantation in 2003-2010 and had serial antibody monitoring by solid-phase assays at baseline (the time of transplantation) and at 1, 3, 6, 9, and 12 months, at minimum.

"More recently introduced methods using solid-phase matrices coated with HLA antigens have demonstrated the ability to detect and identify HLA antibodies with high sensitivity and accuracy," he said.

Because the study period preceded the guidelines that recommended antibody monitoring, these patients were being followed more closely than usual out of concern that they were at heightened risk for antibody development, he said.

On average, the patients had seven antibody measurements during their first year post transplantation.

Study results showed that in the first year after transplantation, 14% of patients developed DSA and 32% developed non–donor-specific antibodies (non-DSA), while the rest did not develop any.

The mean age (approximately 53 years) was similar across groups. Relative to those who did not develop any antibodies, patients who developed non-DSA were more likely to be female (54% vs. 22%). Also, ischemic time was shorter for patients who developed DSA (183 minutes) or non-DSA (195 minutes) than for their counterparts who did not develop any antibodies (230 minutes).

The three groups of patients were generally similar with respect to immunosuppressive therapy at baseline, including receipt of calcineurin inhibitors and antiproliferative agents.

But the group developing DSA was significantly less likely than the group not developing antibodies to be weaned off prednisone (7% vs. 46%), and both the DSA and non-DSA groups were more likely than their counterparts with no antibodies to have received induction therapy (45% and 39% vs. 15%).

The 1-year rate of freedom from antibody-mediated rejection was poorer for patients who developed DSA (65%) or non-DSA (76%), compared with their peers who developed no antibodies (94%). The findings were similar with respect to rates of freedom from acute cellular rejection (80% and 87% vs. 99%, respectively).

The temporal patterns did differ somewhat according to type of rejection, according to Dr. Patel.

"With regard to cellular rejection, it appeared that a lot of events in the patients who developed donor-specific antibodies occurred toward the end of the first year, in comparison to the patients who developed antibody-mediated rejection, where most of the events tended to occur early" post transplant, he observed.

Relative to their counterparts who did not develop antibodies, the patients who developed DSA also had significantly poorer 3-year rates of survival (65% vs. 85%) and freedom from cardiac allograft vasculopathy, which was defined as the development of vascular stenosis exceeding 30% (70% vs. 88%).

Dr. Patel reported that he had no conflicts of interest related to the study.