SAN ANTONIO — A single, intravenous injection of methylprednisolone performed just slightly better than placebo in alleviating pain from acute discogenic sciatica, Axel Finckh, M.D., said at the annual meeting of the American College of Rheumatology.

Dr. Finckh presented a study in which 59 patients with radiographically confirmed discogenic sciatica were randomized to either a single, 500-mg, intravenous bolus of methylprednisolone or to placebo, and then followed for 10 days.

Both groups had significant improvement in pain on the first day, as shown with a 100-point, visual analog scale, with a greater mean improvement for the methylprednisolone group.

However, mean scores in both groups were about the same by the third day and remained comparable through day 10.

Both groups had gradual diminishment of pain from day 3 onward, said Dr. Finckh, of Brigham and Women's Hospital, Boston.

Nor were response rates significantly different on a straight leg test for radicular irritation, a McGill Pain Score for global pain, a flexibility score, and a functional disability questionnaire, Dr. Finckh explained.

The patients in the study had all had sciatica for at least 1 week, and not more than 6 weeks, prior to being treated.

Use of nonsteroidal anti-inflammatory drugs was permitted.

The use of corticosteroids in sciatica is controversial, Dr. Finckh said.

Most studies of oral administration have not demonstrated any benefit.

Some studies of epidural administration, however, have shown positive findings.

His group conducted the study because they hypothesized that giving the corticosteroid intravenously might be a way to achieve high drug levels quickly, without the risks and pain typically associated with epidural administration.

Despite the negative results, Dr. Finckh seemed unwilling to give up completely on intravenous injection for sciatica.

He noted that 48% of the steroid-treated patients had pain improvement, versus 28% of the placebo patients.

Long-term treatment using the technique might have more of an effect, he said.

SAN ANTONIO — A single, intravenous injection of methylprednisolone performed just slightly better than placebo in alleviating pain from acute discogenic sciatica, Axel Finckh, M.D., said at the annual meeting of the American College of Rheumatology.

Dr. Finckh presented a study in which 59 patients with radiographically confirmed discogenic sciatica were randomized to either a single, 500-mg, intravenous bolus of methylprednisolone or to placebo, and then followed for 10 days.

Both groups had significant improvement in pain on the first day, as shown with a 100-point, visual analog scale, with a greater mean improvement for the methylprednisolone group.

However, mean scores in both groups were about the same by the third day and remained comparable through day 10.

Both groups had gradual diminishment of pain from day 3 onward, said Dr. Finckh, of Brigham and Women's Hospital, Boston.

Nor were response rates significantly different on a straight leg test for radicular irritation, a McGill Pain Score for global pain, a flexibility score, and a functional disability questionnaire, Dr. Finckh explained.

The patients in the study had all had sciatica for at least 1 week, and not more than 6 weeks, prior to being treated.

Use of nonsteroidal anti-inflammatory drugs was permitted.

The use of corticosteroids in sciatica is controversial, Dr. Finckh said.

Most studies of oral administration have not demonstrated any benefit.

Some studies of epidural administration, however, have shown positive findings.

His group conducted the study because they hypothesized that giving the corticosteroid intravenously might be a way to achieve high drug levels quickly, without the risks and pain typically associated with epidural administration.

Despite the negative results, Dr. Finckh seemed unwilling to give up completely on intravenous injection for sciatica.

He noted that 48% of the steroid-treated patients had pain improvement, versus 28% of the placebo patients.

Long-term treatment using the technique might have more of an effect, he said.

SAN ANTONIO — A single, intravenous injection of methylprednisolone performed just slightly better than placebo in alleviating pain from acute discogenic sciatica, Axel Finckh, M.D., said at the annual meeting of the American College of Rheumatology.

Dr. Finckh presented a study in which 59 patients with radiographically confirmed discogenic sciatica were randomized to either a single, 500-mg, intravenous bolus of methylprednisolone or to placebo, and then followed for 10 days.

Both groups had significant improvement in pain on the first day, as shown with a 100-point, visual analog scale, with a greater mean improvement for the methylprednisolone group.

However, mean scores in both groups were about the same by the third day and remained comparable through day 10.

Both groups had gradual diminishment of pain from day 3 onward, said Dr. Finckh, of Brigham and Women's Hospital, Boston.

Nor were response rates significantly different on a straight leg test for radicular irritation, a McGill Pain Score for global pain, a flexibility score, and a functional disability questionnaire, Dr. Finckh explained.

The patients in the study had all had sciatica for at least 1 week, and not more than 6 weeks, prior to being treated.

Use of nonsteroidal anti-inflammatory drugs was permitted.

The use of corticosteroids in sciatica is controversial, Dr. Finckh said.

Most studies of oral administration have not demonstrated any benefit.

Some studies of epidural administration, however, have shown positive findings.

His group conducted the study because they hypothesized that giving the corticosteroid intravenously might be a way to achieve high drug levels quickly, without the risks and pain typically associated with epidural administration.

Despite the negative results, Dr. Finckh seemed unwilling to give up completely on intravenous injection for sciatica.

He noted that 48% of the steroid-treated patients had pain improvement, versus 28% of the placebo patients.

Long-term treatment using the technique might have more of an effect, he said.

DÜSSELDORF, GERMANY — After years of relative obscurity, lupus erythematosus tumidus is getting dragged out into the light and painstakingly classified as a distinct subtype of cutaneous lupus erythematosus.

Ever since it was first described in 1930, investigators publishing in non-English language journals have sought to more precisely define the rare and elusive subtype. Meanwhile, English-language journals made no mention of lupus erythematosus tumidus (LET) before 2000.

Today, the collective clinical, photobiologic, histologic, and immunohistochemical evidence appears to firmly classify the disease as a subtype of cutaneous LE, Annegret Kuhn, M.D., said at an international conference on cutaneous lupus erythematosus.

Differential skin conditions, such as discoid LE, subacute cutaneous LE, polymorphic light eruption, Jessner's lymphocytic infiltration, and reticular erythematosus mucinosis, share a variety of LET features, so “the correct diagnosis demands attention to rather subtle detail, characteristic clinical features, as well as the course of the disease,” said Dr. Kuhn, who for the last decade has been seeking to characterize the disease with her colleagues at the University of Düesseldorf, Germany.

Clinically, LET is characterized by erythematosus, urticaria-like, nonscarring plaques with a bright and smooth surface. The swollen appearance of the lesions and the absence of clinically evident epidermal involvement are the most important features of this LE subtype.

In general, skin lesions of lupus tumidus involve sun-exposed areas, such as the face, upper back, arms, and neck, but these lesions have never been detected below the waist, Dr. Kuhn said.

The lesions can disappear intermittently even when the disease is chronic. In some cases, the skin lesions slough in the periphery and flatten in the center, producing an annular configuration. The skin lesions can also appear as multiple, confluent papules, sometimes indicating an eruption.

LET following the lines of Blaschko also has been described (Lupus 2002;11:388-91).

Mostly occurring in adults, only four children have been reported to have LET during the last 10 years.

One 8-year-old boy had erythematosus lesions on his ears that first appeared at 9 months of age. In the following years, he developed lesions on sun-exposed areas of the skin (Dermatology 2003;207:188-92).

Photoprovocation testing can be helpful in diagnosing LET, since the cutaneous subtype may be the most photosensitive type of LE, she said.

Characteristic skin lesions arose in 72% of 60 patients with LET after following a standardized protocol of UVA and UVB irradiation in a study conducted by Dr. Kuhn and her associates (Photochem. Photobiol. 2001;73:532-6). Some of these patients reacted to only UVA (50%) or UVB (48%) or both (63%). About 70% of the patients with a positive phototest reaction denied that sun exposure had an impact on their disease, “which might be due to the latency in developing these lesions after UV irradiation and the difficulty of the patient to relate their skin disease to sun exposure,” Dr. Kuhn said. The investigators also positively correlated the production of antinuclear antibodies with positive phototest reactions.

Both primary and experimentally UV-induced skin lesions display perivascular and periadnexal superficial and deep lymphocytic infiltration containing mostly leukocytes and scattered neutrophils.

In a study of skin biopsy samples from 80 patients, Dr. Kuhn and colleagues found that in contrast with other forms of cutaneous LE, the epidermis is not involved in LET. No changes to the dermal-epidermal junction were found. Colloidal iron staining revealed abundant subepidermal deposits of mucin between collagen bundles (J. Am. Acad. Dermatol. 2003;48:901-8).

The expression of epidermal surface molecules such as intercellular adhesion molecule-1, histocompatibility class II molecules (HLA-DR), and a distinct marker of cell activation and differentiation (27E10) are upregulated in skin biopsy segments of patients with LET to a degree similar to that seen in patients with subacute chronic LE and discoid LE (Br. J. Dermatol. 2002;146:801-9).

Such findings lend weight to the theory that LET represents a distinct subset of cutaneous LE with a similar pathogenic mechanism, rather than a distinct disease, she said.

This patient with LET has erythema-tous, succulent, nonscarring plaques.

Perivascular and periadnexal lympho-cytic infiltration is seen on histology. Photos courtesy Dr. Annegret Kuhn/University of Duesseldorf, Germany

DÜSSELDORF, GERMANY — After years of relative obscurity, lupus erythematosus tumidus is getting dragged out into the light and painstakingly classified as a distinct subtype of cutaneous lupus erythematosus.

Ever since it was first described in 1930, investigators publishing in non-English language journals have sought to more precisely define the rare and elusive subtype. Meanwhile, English-language journals made no mention of lupus erythematosus tumidus (LET) before 2000.

Today, the collective clinical, photobiologic, histologic, and immunohistochemical evidence appears to firmly classify the disease as a subtype of cutaneous LE, Annegret Kuhn, M.D., said at an international conference on cutaneous lupus erythematosus.

Differential skin conditions, such as discoid LE, subacute cutaneous LE, polymorphic light eruption, Jessner's lymphocytic infiltration, and reticular erythematosus mucinosis, share a variety of LET features, so “the correct diagnosis demands attention to rather subtle detail, characteristic clinical features, as well as the course of the disease,” said Dr. Kuhn, who for the last decade has been seeking to characterize the disease with her colleagues at the University of Düesseldorf, Germany.

Clinically, LET is characterized by erythematosus, urticaria-like, nonscarring plaques with a bright and smooth surface. The swollen appearance of the lesions and the absence of clinically evident epidermal involvement are the most important features of this LE subtype.

In general, skin lesions of lupus tumidus involve sun-exposed areas, such as the face, upper back, arms, and neck, but these lesions have never been detected below the waist, Dr. Kuhn said.

The lesions can disappear intermittently even when the disease is chronic. In some cases, the skin lesions slough in the periphery and flatten in the center, producing an annular configuration. The skin lesions can also appear as multiple, confluent papules, sometimes indicating an eruption.

LET following the lines of Blaschko also has been described (Lupus 2002;11:388-91).

Mostly occurring in adults, only four children have been reported to have LET during the last 10 years.

One 8-year-old boy had erythematosus lesions on his ears that first appeared at 9 months of age. In the following years, he developed lesions on sun-exposed areas of the skin (Dermatology 2003;207:188-92).

Photoprovocation testing can be helpful in diagnosing LET, since the cutaneous subtype may be the most photosensitive type of LE, she said.

Characteristic skin lesions arose in 72% of 60 patients with LET after following a standardized protocol of UVA and UVB irradiation in a study conducted by Dr. Kuhn and her associates (Photochem. Photobiol. 2001;73:532-6). Some of these patients reacted to only UVA (50%) or UVB (48%) or both (63%). About 70% of the patients with a positive phototest reaction denied that sun exposure had an impact on their disease, “which might be due to the latency in developing these lesions after UV irradiation and the difficulty of the patient to relate their skin disease to sun exposure,” Dr. Kuhn said. The investigators also positively correlated the production of antinuclear antibodies with positive phototest reactions.

Both primary and experimentally UV-induced skin lesions display perivascular and periadnexal superficial and deep lymphocytic infiltration containing mostly leukocytes and scattered neutrophils.

In a study of skin biopsy samples from 80 patients, Dr. Kuhn and colleagues found that in contrast with other forms of cutaneous LE, the epidermis is not involved in LET. No changes to the dermal-epidermal junction were found. Colloidal iron staining revealed abundant subepidermal deposits of mucin between collagen bundles (J. Am. Acad. Dermatol. 2003;48:901-8).

The expression of epidermal surface molecules such as intercellular adhesion molecule-1, histocompatibility class II molecules (HLA-DR), and a distinct marker of cell activation and differentiation (27E10) are upregulated in skin biopsy segments of patients with LET to a degree similar to that seen in patients with subacute chronic LE and discoid LE (Br. J. Dermatol. 2002;146:801-9).

Such findings lend weight to the theory that LET represents a distinct subset of cutaneous LE with a similar pathogenic mechanism, rather than a distinct disease, she said.

This patient with LET has erythema-tous, succulent, nonscarring plaques.

Perivascular and periadnexal lympho-cytic infiltration is seen on histology. Photos courtesy Dr. Annegret Kuhn/University of Duesseldorf, Germany

DÜSSELDORF, GERMANY — After years of relative obscurity, lupus erythematosus tumidus is getting dragged out into the light and painstakingly classified as a distinct subtype of cutaneous lupus erythematosus.

Ever since it was first described in 1930, investigators publishing in non-English language journals have sought to more precisely define the rare and elusive subtype. Meanwhile, English-language journals made no mention of lupus erythematosus tumidus (LET) before 2000.

Today, the collective clinical, photobiologic, histologic, and immunohistochemical evidence appears to firmly classify the disease as a subtype of cutaneous LE, Annegret Kuhn, M.D., said at an international conference on cutaneous lupus erythematosus.

Differential skin conditions, such as discoid LE, subacute cutaneous LE, polymorphic light eruption, Jessner's lymphocytic infiltration, and reticular erythematosus mucinosis, share a variety of LET features, so “the correct diagnosis demands attention to rather subtle detail, characteristic clinical features, as well as the course of the disease,” said Dr. Kuhn, who for the last decade has been seeking to characterize the disease with her colleagues at the University of Düesseldorf, Germany.

Clinically, LET is characterized by erythematosus, urticaria-like, nonscarring plaques with a bright and smooth surface. The swollen appearance of the lesions and the absence of clinically evident epidermal involvement are the most important features of this LE subtype.

In general, skin lesions of lupus tumidus involve sun-exposed areas, such as the face, upper back, arms, and neck, but these lesions have never been detected below the waist, Dr. Kuhn said.

The lesions can disappear intermittently even when the disease is chronic. In some cases, the skin lesions slough in the periphery and flatten in the center, producing an annular configuration. The skin lesions can also appear as multiple, confluent papules, sometimes indicating an eruption.

LET following the lines of Blaschko also has been described (Lupus 2002;11:388-91).

Mostly occurring in adults, only four children have been reported to have LET during the last 10 years.

One 8-year-old boy had erythematosus lesions on his ears that first appeared at 9 months of age. In the following years, he developed lesions on sun-exposed areas of the skin (Dermatology 2003;207:188-92).

Photoprovocation testing can be helpful in diagnosing LET, since the cutaneous subtype may be the most photosensitive type of LE, she said.

Characteristic skin lesions arose in 72% of 60 patients with LET after following a standardized protocol of UVA and UVB irradiation in a study conducted by Dr. Kuhn and her associates (Photochem. Photobiol. 2001;73:532-6). Some of these patients reacted to only UVA (50%) or UVB (48%) or both (63%). About 70% of the patients with a positive phototest reaction denied that sun exposure had an impact on their disease, “which might be due to the latency in developing these lesions after UV irradiation and the difficulty of the patient to relate their skin disease to sun exposure,” Dr. Kuhn said. The investigators also positively correlated the production of antinuclear antibodies with positive phototest reactions.

Both primary and experimentally UV-induced skin lesions display perivascular and periadnexal superficial and deep lymphocytic infiltration containing mostly leukocytes and scattered neutrophils.

In a study of skin biopsy samples from 80 patients, Dr. Kuhn and colleagues found that in contrast with other forms of cutaneous LE, the epidermis is not involved in LET. No changes to the dermal-epidermal junction were found. Colloidal iron staining revealed abundant subepidermal deposits of mucin between collagen bundles (J. Am. Acad. Dermatol. 2003;48:901-8).

The expression of epidermal surface molecules such as intercellular adhesion molecule-1, histocompatibility class II molecules (HLA-DR), and a distinct marker of cell activation and differentiation (27E10) are upregulated in skin biopsy segments of patients with LET to a degree similar to that seen in patients with subacute chronic LE and discoid LE (Br. J. Dermatol. 2002;146:801-9).

Such findings lend weight to the theory that LET represents a distinct subset of cutaneous LE with a similar pathogenic mechanism, rather than a distinct disease, she said.

This patient with LET has erythema-tous, succulent, nonscarring plaques.

Perivascular and periadnexal lympho-cytic infiltration is seen on histology. Photos courtesy Dr. Annegret Kuhn/University of Duesseldorf, Germany

MUNICH — Systematic screening of patients with systemic sclerosis for pulmonary arterial hypertension can identify patients with this life-threatening complication when it is less severe, based on a screening study with 617 patients.

Diagnosing pulmonary arterial hypertension (PAH) when it is not as advanced makes earlier treatment possible and may lead to better patient outcomes, Dr. Marc Humbert said at the annual congress of the European Society of Cardiology.

Systematic screening of 617 patients at 21 university hospitals in France identified 18 patients with newly diagnosed PAH. When added to the 29 patients from this group who had been previously diagnosed with PAH, there was an overall prevalence of PAH of 7.6% in patients with systemic sclerosis.

This was consistent with prior reports of a PAH prevalence of about 10% in these patients, said Dr. Humbert, a physician in the pulmonology service at Antoine Beclere Hospital, Clamart, France.

The 18 patients with newly diagnosed PAH had an average pulmonary artery pressure at rest of 30 mm Hg, compared with a mean, resting pulmonary artery pressure of 49 mm Hg in the 29 patients with previously diagnosed PAH.

The lower pulmonary artery pressure in the newly diagnosed patients showed that their disease was less advanced, Dr. Humbert said.

The 18 patients with newly-identified PAH had been diagnosed with systemic sclerosis for an average of 8 years.

By comparison, the 29 patients with established PAH had been diagnosed with systemic sclerosis for an average of 12 years.

When PAH develops in patients with systemic sclerosis, it usually appears 6-10 years after the disease manifests.

The screening study organized by Dr. Humbert and his associates enrolled patients who were at least 18 years old and had either diffuse or limited systemic sclerosis. During September 2002 through July 2003, there were 709 patients who met these criteria and were examined at the 21 participating centers.

The key screening measure was an echocardiography examination to assess the tricuspid-valve gradient. Patients who had a tricuspid regurgitation velocity of less than 2.5 m/sec were considered to have a low risk of having PAH and did not undergo additional testing, according to the study protocol.

Patients with a regurgitation velocity of more than 3.0 m/sec had a high risk of PAH and were referred for right heart catheterization.

Patients with a regurgitation velocity that fell within 2.5-3 m/sec were triaged to right heart catheterization if they also had a history of unexplained dyspnea. Patients in this range without a history of unexplained dyspnea did not undergo right heart catheterization.

A total of 92 patients were excluded from the study, mostly because of abnormal lung function or because they had received an incomplete echocardiography examination.

Among the 617 patients who remained in the investigation, 29 had known PAH and did not undergo further testing. Echo examinations of the other 583 patients yielded 51 patients with echo findings consistent with PAH.

Among these 51 patients, 33 agreed to have right heart catheterization, and 18 of these patients were found to have PAH.

An additional three patients were diagnosed with left heart disease.

Among the remaining 12 patients who underwent right heart catheterization, 6 had an elevated pulmonary artery pressure of more than 20 mm Hg, but this elevation failed to meet the minimum criteria for PAH of 25 mm Hg.

Among the 18 patients newly diagnosed with PAH, 14 had mild disease, with a resting pulmonary artery pressure of less than 35 mm Hg.

Another three patients had moderate PAH, with a resting pressure of 35-45 mm Hg, and one patient was diagnosed with severe PAH with a pressure greater than 45 mm Hg.

MUNICH — Systematic screening of patients with systemic sclerosis for pulmonary arterial hypertension can identify patients with this life-threatening complication when it is less severe, based on a screening study with 617 patients.

Diagnosing pulmonary arterial hypertension (PAH) when it is not as advanced makes earlier treatment possible and may lead to better patient outcomes, Dr. Marc Humbert said at the annual congress of the European Society of Cardiology.

Systematic screening of 617 patients at 21 university hospitals in France identified 18 patients with newly diagnosed PAH. When added to the 29 patients from this group who had been previously diagnosed with PAH, there was an overall prevalence of PAH of 7.6% in patients with systemic sclerosis.

This was consistent with prior reports of a PAH prevalence of about 10% in these patients, said Dr. Humbert, a physician in the pulmonology service at Antoine Beclere Hospital, Clamart, France.

The 18 patients with newly diagnosed PAH had an average pulmonary artery pressure at rest of 30 mm Hg, compared with a mean, resting pulmonary artery pressure of 49 mm Hg in the 29 patients with previously diagnosed PAH.

The lower pulmonary artery pressure in the newly diagnosed patients showed that their disease was less advanced, Dr. Humbert said.

The 18 patients with newly-identified PAH had been diagnosed with systemic sclerosis for an average of 8 years.

By comparison, the 29 patients with established PAH had been diagnosed with systemic sclerosis for an average of 12 years.

When PAH develops in patients with systemic sclerosis, it usually appears 6-10 years after the disease manifests.

The screening study organized by Dr. Humbert and his associates enrolled patients who were at least 18 years old and had either diffuse or limited systemic sclerosis. During September 2002 through July 2003, there were 709 patients who met these criteria and were examined at the 21 participating centers.

The key screening measure was an echocardiography examination to assess the tricuspid-valve gradient. Patients who had a tricuspid regurgitation velocity of less than 2.5 m/sec were considered to have a low risk of having PAH and did not undergo additional testing, according to the study protocol.

Patients with a regurgitation velocity of more than 3.0 m/sec had a high risk of PAH and were referred for right heart catheterization.

Patients with a regurgitation velocity that fell within 2.5-3 m/sec were triaged to right heart catheterization if they also had a history of unexplained dyspnea. Patients in this range without a history of unexplained dyspnea did not undergo right heart catheterization.

A total of 92 patients were excluded from the study, mostly because of abnormal lung function or because they had received an incomplete echocardiography examination.

Among the 617 patients who remained in the investigation, 29 had known PAH and did not undergo further testing. Echo examinations of the other 583 patients yielded 51 patients with echo findings consistent with PAH.

Among these 51 patients, 33 agreed to have right heart catheterization, and 18 of these patients were found to have PAH.

An additional three patients were diagnosed with left heart disease.

Among the remaining 12 patients who underwent right heart catheterization, 6 had an elevated pulmonary artery pressure of more than 20 mm Hg, but this elevation failed to meet the minimum criteria for PAH of 25 mm Hg.

Among the 18 patients newly diagnosed with PAH, 14 had mild disease, with a resting pulmonary artery pressure of less than 35 mm Hg.

Another three patients had moderate PAH, with a resting pressure of 35-45 mm Hg, and one patient was diagnosed with severe PAH with a pressure greater than 45 mm Hg.

MUNICH — Systematic screening of patients with systemic sclerosis for pulmonary arterial hypertension can identify patients with this life-threatening complication when it is less severe, based on a screening study with 617 patients.

Diagnosing pulmonary arterial hypertension (PAH) when it is not as advanced makes earlier treatment possible and may lead to better patient outcomes, Dr. Marc Humbert said at the annual congress of the European Society of Cardiology.

Systematic screening of 617 patients at 21 university hospitals in France identified 18 patients with newly diagnosed PAH. When added to the 29 patients from this group who had been previously diagnosed with PAH, there was an overall prevalence of PAH of 7.6% in patients with systemic sclerosis.

This was consistent with prior reports of a PAH prevalence of about 10% in these patients, said Dr. Humbert, a physician in the pulmonology service at Antoine Beclere Hospital, Clamart, France.

The 18 patients with newly diagnosed PAH had an average pulmonary artery pressure at rest of 30 mm Hg, compared with a mean, resting pulmonary artery pressure of 49 mm Hg in the 29 patients with previously diagnosed PAH.

The lower pulmonary artery pressure in the newly diagnosed patients showed that their disease was less advanced, Dr. Humbert said.

The 18 patients with newly-identified PAH had been diagnosed with systemic sclerosis for an average of 8 years.

By comparison, the 29 patients with established PAH had been diagnosed with systemic sclerosis for an average of 12 years.

When PAH develops in patients with systemic sclerosis, it usually appears 6-10 years after the disease manifests.

The screening study organized by Dr. Humbert and his associates enrolled patients who were at least 18 years old and had either diffuse or limited systemic sclerosis. During September 2002 through July 2003, there were 709 patients who met these criteria and were examined at the 21 participating centers.

The key screening measure was an echocardiography examination to assess the tricuspid-valve gradient. Patients who had a tricuspid regurgitation velocity of less than 2.5 m/sec were considered to have a low risk of having PAH and did not undergo additional testing, according to the study protocol.

Patients with a regurgitation velocity of more than 3.0 m/sec had a high risk of PAH and were referred for right heart catheterization.

Patients with a regurgitation velocity that fell within 2.5-3 m/sec were triaged to right heart catheterization if they also had a history of unexplained dyspnea. Patients in this range without a history of unexplained dyspnea did not undergo right heart catheterization.

A total of 92 patients were excluded from the study, mostly because of abnormal lung function or because they had received an incomplete echocardiography examination.

Among the 617 patients who remained in the investigation, 29 had known PAH and did not undergo further testing. Echo examinations of the other 583 patients yielded 51 patients with echo findings consistent with PAH.

Among these 51 patients, 33 agreed to have right heart catheterization, and 18 of these patients were found to have PAH.

An additional three patients were diagnosed with left heart disease.

Among the remaining 12 patients who underwent right heart catheterization, 6 had an elevated pulmonary artery pressure of more than 20 mm Hg, but this elevation failed to meet the minimum criteria for PAH of 25 mm Hg.

Among the 18 patients newly diagnosed with PAH, 14 had mild disease, with a resting pulmonary artery pressure of less than 35 mm Hg.

Another three patients had moderate PAH, with a resting pressure of 35-45 mm Hg, and one patient was diagnosed with severe PAH with a pressure greater than 45 mm Hg.

SAN ANTONIO — The current and lifetime prevalence of major depression is high among patients with scleroderma, an underrecognized fact that can no longer be ignored, Thierry Baubet, M.D., said at the annual meeting of the American College of Rheumatology.

Among 94 patients with systemic sclerosis seen in two French medical centers between May 2002 and May 2004, 17 (18%) had a current diagnosis of major depression, 50 (53%) had a lifetime diagnosis of major depression, and 7 (7%) had a current diagnosis of dysthymia. Moreover, 12 had a history of suicide attempts, and 31 were judged to have a moderate to severe ongoing suicide risk, he said.

The patients ranged in age from 26 to 85 years, and 81 were women. Psychiatric assessment was done using the Mini-International Neuropsychiatric Interview, the French DSM-IV, the 13-item Beck depression inventory, and the hospital anxiety and depression scale.

Additional information regarding past and current psychiatric treatment was sought with a structured questionnaire.

Fewer than half of patients with affective disorders had received psychiatric treatment, said Dr. Baubet of the psychiatric service, Avicenne Hospital, Bobigny (France).

Anxiety disorders also were common in this cohort, being diagnosed in 35 patients. Social phobia and generalized anxiety each were diagnosed in 13 patients, agoraphobia without panic disorder was diagnosed in 9, panic disorder in 6, posttraumatic stress disorder in 2, and obsessive compulsive disorder in 1. Some patients had more than one anxiety diagnosis.

Depression and anxiety are common and frequently overlooked in patients with systemic sclerosis, Dr. Baubet said in a poster session.

“Systematic screening and psychiatric treatment interventions are needed,” he said.

SAN ANTONIO — The current and lifetime prevalence of major depression is high among patients with scleroderma, an underrecognized fact that can no longer be ignored, Thierry Baubet, M.D., said at the annual meeting of the American College of Rheumatology.

Among 94 patients with systemic sclerosis seen in two French medical centers between May 2002 and May 2004, 17 (18%) had a current diagnosis of major depression, 50 (53%) had a lifetime diagnosis of major depression, and 7 (7%) had a current diagnosis of dysthymia. Moreover, 12 had a history of suicide attempts, and 31 were judged to have a moderate to severe ongoing suicide risk, he said.

The patients ranged in age from 26 to 85 years, and 81 were women. Psychiatric assessment was done using the Mini-International Neuropsychiatric Interview, the French DSM-IV, the 13-item Beck depression inventory, and the hospital anxiety and depression scale.

Additional information regarding past and current psychiatric treatment was sought with a structured questionnaire.

Fewer than half of patients with affective disorders had received psychiatric treatment, said Dr. Baubet of the psychiatric service, Avicenne Hospital, Bobigny (France).

Anxiety disorders also were common in this cohort, being diagnosed in 35 patients. Social phobia and generalized anxiety each were diagnosed in 13 patients, agoraphobia without panic disorder was diagnosed in 9, panic disorder in 6, posttraumatic stress disorder in 2, and obsessive compulsive disorder in 1. Some patients had more than one anxiety diagnosis.

Depression and anxiety are common and frequently overlooked in patients with systemic sclerosis, Dr. Baubet said in a poster session.

“Systematic screening and psychiatric treatment interventions are needed,” he said.

SAN ANTONIO — The current and lifetime prevalence of major depression is high among patients with scleroderma, an underrecognized fact that can no longer be ignored, Thierry Baubet, M.D., said at the annual meeting of the American College of Rheumatology.

Among 94 patients with systemic sclerosis seen in two French medical centers between May 2002 and May 2004, 17 (18%) had a current diagnosis of major depression, 50 (53%) had a lifetime diagnosis of major depression, and 7 (7%) had a current diagnosis of dysthymia. Moreover, 12 had a history of suicide attempts, and 31 were judged to have a moderate to severe ongoing suicide risk, he said.

The patients ranged in age from 26 to 85 years, and 81 were women. Psychiatric assessment was done using the Mini-International Neuropsychiatric Interview, the French DSM-IV, the 13-item Beck depression inventory, and the hospital anxiety and depression scale.

Additional information regarding past and current psychiatric treatment was sought with a structured questionnaire.

Fewer than half of patients with affective disorders had received psychiatric treatment, said Dr. Baubet of the psychiatric service, Avicenne Hospital, Bobigny (France).

Anxiety disorders also were common in this cohort, being diagnosed in 35 patients. Social phobia and generalized anxiety each were diagnosed in 13 patients, agoraphobia without panic disorder was diagnosed in 9, panic disorder in 6, posttraumatic stress disorder in 2, and obsessive compulsive disorder in 1. Some patients had more than one anxiety diagnosis.

Depression and anxiety are common and frequently overlooked in patients with systemic sclerosis, Dr. Baubet said in a poster session.

“Systematic screening and psychiatric treatment interventions are needed,” he said.

SEATTLE — A 12-week course of sildenafil citrate in adults with pulmonary arterial hypertension significantly improved 6-minute walking distance and mean pulmonary artery pressure, and had favorable effects on New York Heart Association functional class, H. Ardeschir Ghofrani, M.D., reported at the annual meeting of the American College of Chest Physicians.

“Sildenafil was not only highly effective in achieving improvement in 6-minute walking distance, but it also showed a very favorable safety profile,” he said in an interview.

It appears to be a very “good drug” for treating pulmonary arterial hypertension, but as promising as these data appear, physicians should not use the drug off label, as “this really should be addressed in controlled trials,” Dr. Ghofrani said.

In a multicenter, international trial, Dr. Ghofrani and his associates enrolled 278 patients with pulmonary hypertension and randomized them to placebo or sildenafil three times daily for 12 weeks.

Most of the patients (75%) were female, and the average age was 49. Overall, 63% had primary pulmonary hypertension and 30% had connective tissue disease. Most of the patients (58%) had New York Heart Association functional class III disease and 39% had class II disease.

Of the 278 patients, 70 took placebo t.i.d., 69 took 20 mg sildenafil t.i.d., 68 took 40 mg sildenafil t.i.d., and 71 took 80 mg sildenafil t.i.d.

The primary end point was change from baseline at week 12 in exercise capacity as measured by 6-minute walking distance.

Compared with patients who took a placebo, those assigned to take sildenafil had significant improvements in 6-minute walking distance.

The mean placebo-corrected treatment effect was 45 meters in the 20-mg group, 46 meters in the 40-mg group, and 50 meters in the 80-mg group.

“The improvements were slightly more pronounced in patients who had lower 6-minute walking distances at baseline, showing improvements up to 80 meters in the 80-mg group, whereas the patients who were doing better at baseline still had significant improvements,” said Dr. Ghofrani of Giessen, Germany, who is a paid consultant to Pfizer, which manufactures sildenafil.

All sildenafil doses reduced mean pulmonary artery pressure by week 12. The mean reductions were 2.7 mm Hg in the 20-mg group, 3.0 mm Hg in the 40-mg group, and 5.1 mm Hg in the 80-mg group.

The proportion of patients who improved by at least one New York Heart Association functional class was 35% in the sildenafil group and 7% in the placebo group.

The investigators also observed a trend toward decreased hospitalizations and improvements in shortness of breath during exercise among patients on sildenafil.

The most common adverse events experienced by patients on sildenafil, compared with those on placebo, were headache, flushing, dyspepsia, and back pain.

Pfizer Global Research and Development funded the study.

SEATTLE — A 12-week course of sildenafil citrate in adults with pulmonary arterial hypertension significantly improved 6-minute walking distance and mean pulmonary artery pressure, and had favorable effects on New York Heart Association functional class, H. Ardeschir Ghofrani, M.D., reported at the annual meeting of the American College of Chest Physicians.

“Sildenafil was not only highly effective in achieving improvement in 6-minute walking distance, but it also showed a very favorable safety profile,” he said in an interview.

It appears to be a very “good drug” for treating pulmonary arterial hypertension, but as promising as these data appear, physicians should not use the drug off label, as “this really should be addressed in controlled trials,” Dr. Ghofrani said.

In a multicenter, international trial, Dr. Ghofrani and his associates enrolled 278 patients with pulmonary hypertension and randomized them to placebo or sildenafil three times daily for 12 weeks.

Most of the patients (75%) were female, and the average age was 49. Overall, 63% had primary pulmonary hypertension and 30% had connective tissue disease. Most of the patients (58%) had New York Heart Association functional class III disease and 39% had class II disease.

Of the 278 patients, 70 took placebo t.i.d., 69 took 20 mg sildenafil t.i.d., 68 took 40 mg sildenafil t.i.d., and 71 took 80 mg sildenafil t.i.d.

The primary end point was change from baseline at week 12 in exercise capacity as measured by 6-minute walking distance.

Compared with patients who took a placebo, those assigned to take sildenafil had significant improvements in 6-minute walking distance.

The mean placebo-corrected treatment effect was 45 meters in the 20-mg group, 46 meters in the 40-mg group, and 50 meters in the 80-mg group.

“The improvements were slightly more pronounced in patients who had lower 6-minute walking distances at baseline, showing improvements up to 80 meters in the 80-mg group, whereas the patients who were doing better at baseline still had significant improvements,” said Dr. Ghofrani of Giessen, Germany, who is a paid consultant to Pfizer, which manufactures sildenafil.

All sildenafil doses reduced mean pulmonary artery pressure by week 12. The mean reductions were 2.7 mm Hg in the 20-mg group, 3.0 mm Hg in the 40-mg group, and 5.1 mm Hg in the 80-mg group.

The proportion of patients who improved by at least one New York Heart Association functional class was 35% in the sildenafil group and 7% in the placebo group.

The investigators also observed a trend toward decreased hospitalizations and improvements in shortness of breath during exercise among patients on sildenafil.

The most common adverse events experienced by patients on sildenafil, compared with those on placebo, were headache, flushing, dyspepsia, and back pain.

Pfizer Global Research and Development funded the study.

SEATTLE — A 12-week course of sildenafil citrate in adults with pulmonary arterial hypertension significantly improved 6-minute walking distance and mean pulmonary artery pressure, and had favorable effects on New York Heart Association functional class, H. Ardeschir Ghofrani, M.D., reported at the annual meeting of the American College of Chest Physicians.

“Sildenafil was not only highly effective in achieving improvement in 6-minute walking distance, but it also showed a very favorable safety profile,” he said in an interview.

It appears to be a very “good drug” for treating pulmonary arterial hypertension, but as promising as these data appear, physicians should not use the drug off label, as “this really should be addressed in controlled trials,” Dr. Ghofrani said.

In a multicenter, international trial, Dr. Ghofrani and his associates enrolled 278 patients with pulmonary hypertension and randomized them to placebo or sildenafil three times daily for 12 weeks.

Most of the patients (75%) were female, and the average age was 49. Overall, 63% had primary pulmonary hypertension and 30% had connective tissue disease. Most of the patients (58%) had New York Heart Association functional class III disease and 39% had class II disease.

Of the 278 patients, 70 took placebo t.i.d., 69 took 20 mg sildenafil t.i.d., 68 took 40 mg sildenafil t.i.d., and 71 took 80 mg sildenafil t.i.d.

The primary end point was change from baseline at week 12 in exercise capacity as measured by 6-minute walking distance.

Compared with patients who took a placebo, those assigned to take sildenafil had significant improvements in 6-minute walking distance.

The mean placebo-corrected treatment effect was 45 meters in the 20-mg group, 46 meters in the 40-mg group, and 50 meters in the 80-mg group.

“The improvements were slightly more pronounced in patients who had lower 6-minute walking distances at baseline, showing improvements up to 80 meters in the 80-mg group, whereas the patients who were doing better at baseline still had significant improvements,” said Dr. Ghofrani of Giessen, Germany, who is a paid consultant to Pfizer, which manufactures sildenafil.

All sildenafil doses reduced mean pulmonary artery pressure by week 12. The mean reductions were 2.7 mm Hg in the 20-mg group, 3.0 mm Hg in the 40-mg group, and 5.1 mm Hg in the 80-mg group.

The proportion of patients who improved by at least one New York Heart Association functional class was 35% in the sildenafil group and 7% in the placebo group.

The investigators also observed a trend toward decreased hospitalizations and improvements in shortness of breath during exercise among patients on sildenafil.

The most common adverse events experienced by patients on sildenafil, compared with those on placebo, were headache, flushing, dyspepsia, and back pain.

Pfizer Global Research and Development funded the study.

WASHINGTON — A new minimally invasive surgical technique could considerably improve the prognosis for infants born with hypoplastic left heart syndrome, Emile Bacha, M.D., said at a conference for science reporters sponsored by the American Medical Association.

Hyperplastic left heart syndrome (HLS), one of the most severe congenital heart defects, occurs in approximately 0.016%–0.036% of all live births in the United States, said Dr. Bacha, a pediatric cardiologic surgeon at the University of Chicago.

HLS is most often treated with a set of three extremely invasive, delicate open-heart surgical procedures aimed at providing unobstructed outflow to the heart via a single ventricle system and unobstructed pulmonary venous return, while shunting a portion of the blood away to feed the lungs and provide gas exchange.

Stage I, the Norwood operation, is performed within days of life. Stage II, the Glenn operation, follows at 6 months, while the stage III Fontan operation is done at 24 months.

Although 80%-90% of infants survive the Norwood stage I, about 10%-15% die before reaching the second procedure. Many infants who survive the entire series have below average IQ, abnormal neurologic development, and diminished quality of life.

Hybrid therapy, a combination of interventional cardiology and pediatric cardiac surgery techniques, replaces the traditional open-heart Norwood stage I operation with a palliative beating-heart procedure, he explained. Rather than cooling the body and putting the newborn on heart bypass for a lengthy period, the hybrid stage I is conducted in a specially outfitted catheterization laboratory that includes extra-corporeal circulation membrane oxygenation pump backup. (See illustration.)

Dr. Bacha and his colleague Ziyad M. Hijazi, M.D., have performed the procedure on 10 high-risk newborns (weight 2.2–3.3 kg) with HLS, of whom 6 also had aortic atresia, and 3 each had a major noncardiac anomaly, poor ventricular function, and/or weight less than 2.5 kg. Two were older than 30 days, one presented in shock, and one was born at less than 34 weeks' gestation. One infant died in the hospital following the procedure, resulting in the same hospital survival rate as the traditional Norwood stage I. Another died before reaching the second stage. Seven of the remaining eight have now undergone the Glenn stage II, of whom six have survived.

The Glenn and Fontan procedures are still necessary after hybrid stage I, but Dr. Bacha believes the elimination of one of three traumatic “pump runs” over the first 2 years of life and the postponement of the first beyond the neonatal period may reduce the neurologic complications often associated with bypass procedures.

The hybrid procedure itself and the length of hospital stay were considerably shorter than with the traditional Norwood procedure. One disadvantage of the hybrid technique is that the Glenn procedure is more complicated, since the aortic arch must be reconstructed while the previously implanted stent is removed.

“You're now doing the open-heart surgery on a 3− to 6-month-old, rather than a 5-day-old. … That is a huge difference in terms of sensitivity to trauma and brain maturity,” Dr. Bacha said. Several newer technologies, including therapeutic ultrasound and absorbable stents, will improve the feasibility of the procedure, he said.

EMILY BRANNAN, ILLUSTRATION

WASHINGTON — A new minimally invasive surgical technique could considerably improve the prognosis for infants born with hypoplastic left heart syndrome, Emile Bacha, M.D., said at a conference for science reporters sponsored by the American Medical Association.

Hyperplastic left heart syndrome (HLS), one of the most severe congenital heart defects, occurs in approximately 0.016%–0.036% of all live births in the United States, said Dr. Bacha, a pediatric cardiologic surgeon at the University of Chicago.

HLS is most often treated with a set of three extremely invasive, delicate open-heart surgical procedures aimed at providing unobstructed outflow to the heart via a single ventricle system and unobstructed pulmonary venous return, while shunting a portion of the blood away to feed the lungs and provide gas exchange.

Stage I, the Norwood operation, is performed within days of life. Stage II, the Glenn operation, follows at 6 months, while the stage III Fontan operation is done at 24 months.

Although 80%-90% of infants survive the Norwood stage I, about 10%-15% die before reaching the second procedure. Many infants who survive the entire series have below average IQ, abnormal neurologic development, and diminished quality of life.

Hybrid therapy, a combination of interventional cardiology and pediatric cardiac surgery techniques, replaces the traditional open-heart Norwood stage I operation with a palliative beating-heart procedure, he explained. Rather than cooling the body and putting the newborn on heart bypass for a lengthy period, the hybrid stage I is conducted in a specially outfitted catheterization laboratory that includes extra-corporeal circulation membrane oxygenation pump backup. (See illustration.)

Dr. Bacha and his colleague Ziyad M. Hijazi, M.D., have performed the procedure on 10 high-risk newborns (weight 2.2–3.3 kg) with HLS, of whom 6 also had aortic atresia, and 3 each had a major noncardiac anomaly, poor ventricular function, and/or weight less than 2.5 kg. Two were older than 30 days, one presented in shock, and one was born at less than 34 weeks' gestation. One infant died in the hospital following the procedure, resulting in the same hospital survival rate as the traditional Norwood stage I. Another died before reaching the second stage. Seven of the remaining eight have now undergone the Glenn stage II, of whom six have survived.

The Glenn and Fontan procedures are still necessary after hybrid stage I, but Dr. Bacha believes the elimination of one of three traumatic “pump runs” over the first 2 years of life and the postponement of the first beyond the neonatal period may reduce the neurologic complications often associated with bypass procedures.

The hybrid procedure itself and the length of hospital stay were considerably shorter than with the traditional Norwood procedure. One disadvantage of the hybrid technique is that the Glenn procedure is more complicated, since the aortic arch must be reconstructed while the previously implanted stent is removed.

“You're now doing the open-heart surgery on a 3− to 6-month-old, rather than a 5-day-old. … That is a huge difference in terms of sensitivity to trauma and brain maturity,” Dr. Bacha said. Several newer technologies, including therapeutic ultrasound and absorbable stents, will improve the feasibility of the procedure, he said.

EMILY BRANNAN, ILLUSTRATION

WASHINGTON — A new minimally invasive surgical technique could considerably improve the prognosis for infants born with hypoplastic left heart syndrome, Emile Bacha, M.D., said at a conference for science reporters sponsored by the American Medical Association.

Hyperplastic left heart syndrome (HLS), one of the most severe congenital heart defects, occurs in approximately 0.016%–0.036% of all live births in the United States, said Dr. Bacha, a pediatric cardiologic surgeon at the University of Chicago.

HLS is most often treated with a set of three extremely invasive, delicate open-heart surgical procedures aimed at providing unobstructed outflow to the heart via a single ventricle system and unobstructed pulmonary venous return, while shunting a portion of the blood away to feed the lungs and provide gas exchange.

Stage I, the Norwood operation, is performed within days of life. Stage II, the Glenn operation, follows at 6 months, while the stage III Fontan operation is done at 24 months.

Although 80%-90% of infants survive the Norwood stage I, about 10%-15% die before reaching the second procedure. Many infants who survive the entire series have below average IQ, abnormal neurologic development, and diminished quality of life.

Hybrid therapy, a combination of interventional cardiology and pediatric cardiac surgery techniques, replaces the traditional open-heart Norwood stage I operation with a palliative beating-heart procedure, he explained. Rather than cooling the body and putting the newborn on heart bypass for a lengthy period, the hybrid stage I is conducted in a specially outfitted catheterization laboratory that includes extra-corporeal circulation membrane oxygenation pump backup. (See illustration.)

Dr. Bacha and his colleague Ziyad M. Hijazi, M.D., have performed the procedure on 10 high-risk newborns (weight 2.2–3.3 kg) with HLS, of whom 6 also had aortic atresia, and 3 each had a major noncardiac anomaly, poor ventricular function, and/or weight less than 2.5 kg. Two were older than 30 days, one presented in shock, and one was born at less than 34 weeks' gestation. One infant died in the hospital following the procedure, resulting in the same hospital survival rate as the traditional Norwood stage I. Another died before reaching the second stage. Seven of the remaining eight have now undergone the Glenn stage II, of whom six have survived.

The Glenn and Fontan procedures are still necessary after hybrid stage I, but Dr. Bacha believes the elimination of one of three traumatic “pump runs” over the first 2 years of life and the postponement of the first beyond the neonatal period may reduce the neurologic complications often associated with bypass procedures.

The hybrid procedure itself and the length of hospital stay were considerably shorter than with the traditional Norwood procedure. One disadvantage of the hybrid technique is that the Glenn procedure is more complicated, since the aortic arch must be reconstructed while the previously implanted stent is removed.

“You're now doing the open-heart surgery on a 3− to 6-month-old, rather than a 5-day-old. … That is a huge difference in terms of sensitivity to trauma and brain maturity,” Dr. Bacha said. Several newer technologies, including therapeutic ultrasound and absorbable stents, will improve the feasibility of the procedure, he said.

EMILY BRANNAN, ILLUSTRATION

MUNICH — A novel surgical method reduces the left ventricular volume of patients with cardiomyopathy without using ventriculectomy.

The surgery realigns the papillary muscles of the left ventricle and reduces left ventricular volume by placing three sutures through the trabeculae around the bases of the anterior and posterior muscles, Diane Barker, M.B., said at the annual congress of the European Society of Cardiology.

The procedure, which involves graded placation of the papillary muscle through a small, apical incision, usually takes about 15–20 minutes, said Dr. Barker, a cardiologist at Leeds (England) General Infirmary. The suturing also reduces functional mitral regurgitation. It is generally combined with coronary bypass grafting.

Unnikrishnan R. Nair, M.B., who developed the new technique, has used it to treat 30 patients in Leeds since 1998. Follow-up has ranged from 12 to 58 months, with an average of 28 months. One patient died within 30 days of the procedure from sepsis. Another patient developed atrial fibrillation following surgery. All of the other patients had improvements in their left ventricular function and in their clinical status, and none developed ventricular arrhythmias, Dr. Barker reported. Three patients died 4–24 months following surgery, but the deaths appeared unrelated to surgery. The average age of the patients was 61 years, and three-quarters were men. All of the patients had ischemic cardiomyopathy. The average left ventricular volume of patients before the surgery was 271 mL; after surgery, 230 mL. Before surgery, the patients had heart failure with an average New York Heart Association functional classification of 2.8; after surgery, the average was 1.4.

To better assess this surgery, Dr. Barker and Dr. Nair compared 8 patients who underwent suturing of papillary muscle plus bypass surgery with 32 similar patients treated with bypass surgery only. (See box.)

Exercise duration improved among patients who underwent papillary muscle suturing compared with those who had bypass surgery only. Peak oxygen capacity rose among the patients treated with papillary muscle suturing compared with those who had bypass surgery only. Cardiac reserve rose among patients treated compared with the control group.

The next step is to test the surgery's safety and efficacy in a randomized, controlled study, Dr. Barker said.

This image shows the placement of the sutures through the trabeculae.

This image shows the sutures being tied in the novel procedure.

This image shows the surgical incision being repaired. Photos courtesy Dr. Unnikrishnan R. Nair

MUNICH — A novel surgical method reduces the left ventricular volume of patients with cardiomyopathy without using ventriculectomy.

The surgery realigns the papillary muscles of the left ventricle and reduces left ventricular volume by placing three sutures through the trabeculae around the bases of the anterior and posterior muscles, Diane Barker, M.B., said at the annual congress of the European Society of Cardiology.

The procedure, which involves graded placation of the papillary muscle through a small, apical incision, usually takes about 15–20 minutes, said Dr. Barker, a cardiologist at Leeds (England) General Infirmary. The suturing also reduces functional mitral regurgitation. It is generally combined with coronary bypass grafting.

Unnikrishnan R. Nair, M.B., who developed the new technique, has used it to treat 30 patients in Leeds since 1998. Follow-up has ranged from 12 to 58 months, with an average of 28 months. One patient died within 30 days of the procedure from sepsis. Another patient developed atrial fibrillation following surgery. All of the other patients had improvements in their left ventricular function and in their clinical status, and none developed ventricular arrhythmias, Dr. Barker reported. Three patients died 4–24 months following surgery, but the deaths appeared unrelated to surgery. The average age of the patients was 61 years, and three-quarters were men. All of the patients had ischemic cardiomyopathy. The average left ventricular volume of patients before the surgery was 271 mL; after surgery, 230 mL. Before surgery, the patients had heart failure with an average New York Heart Association functional classification of 2.8; after surgery, the average was 1.4.

To better assess this surgery, Dr. Barker and Dr. Nair compared 8 patients who underwent suturing of papillary muscle plus bypass surgery with 32 similar patients treated with bypass surgery only. (See box.)

Exercise duration improved among patients who underwent papillary muscle suturing compared with those who had bypass surgery only. Peak oxygen capacity rose among the patients treated with papillary muscle suturing compared with those who had bypass surgery only. Cardiac reserve rose among patients treated compared with the control group.

The next step is to test the surgery's safety and efficacy in a randomized, controlled study, Dr. Barker said.

This image shows the placement of the sutures through the trabeculae.

This image shows the sutures being tied in the novel procedure.

This image shows the surgical incision being repaired. Photos courtesy Dr. Unnikrishnan R. Nair

MUNICH — A novel surgical method reduces the left ventricular volume of patients with cardiomyopathy without using ventriculectomy.

The surgery realigns the papillary muscles of the left ventricle and reduces left ventricular volume by placing three sutures through the trabeculae around the bases of the anterior and posterior muscles, Diane Barker, M.B., said at the annual congress of the European Society of Cardiology.

The procedure, which involves graded placation of the papillary muscle through a small, apical incision, usually takes about 15–20 minutes, said Dr. Barker, a cardiologist at Leeds (England) General Infirmary. The suturing also reduces functional mitral regurgitation. It is generally combined with coronary bypass grafting.

Unnikrishnan R. Nair, M.B., who developed the new technique, has used it to treat 30 patients in Leeds since 1998. Follow-up has ranged from 12 to 58 months, with an average of 28 months. One patient died within 30 days of the procedure from sepsis. Another patient developed atrial fibrillation following surgery. All of the other patients had improvements in their left ventricular function and in their clinical status, and none developed ventricular arrhythmias, Dr. Barker reported. Three patients died 4–24 months following surgery, but the deaths appeared unrelated to surgery. The average age of the patients was 61 years, and three-quarters were men. All of the patients had ischemic cardiomyopathy. The average left ventricular volume of patients before the surgery was 271 mL; after surgery, 230 mL. Before surgery, the patients had heart failure with an average New York Heart Association functional classification of 2.8; after surgery, the average was 1.4.

To better assess this surgery, Dr. Barker and Dr. Nair compared 8 patients who underwent suturing of papillary muscle plus bypass surgery with 32 similar patients treated with bypass surgery only. (See box.)

Exercise duration improved among patients who underwent papillary muscle suturing compared with those who had bypass surgery only. Peak oxygen capacity rose among the patients treated with papillary muscle suturing compared with those who had bypass surgery only. Cardiac reserve rose among patients treated compared with the control group.

The next step is to test the surgery's safety and efficacy in a randomized, controlled study, Dr. Barker said.

This image shows the placement of the sutures through the trabeculae.

This image shows the sutures being tied in the novel procedure.

This image shows the surgical incision being repaired. Photos courtesy Dr. Unnikrishnan R. Nair

SAN FRANCISCO — In some patients being evaluated for chest pain, stress tests might be avoided through the use of an algorithm designed to predict the probability of cardiac ischemia, David D. Moyer-Diener and his associates said at the annual meeting of the American College of Emergency Physicians.

In a prospective, observational cohort study of consecutive patients evaluated at a chest pain center, investigators obtained Acute Coronary Ischemia-Time Insensitive Predictive Instrument (ACI-TIPI) scores and conventional chest pain work-ups on 1,478 low- or intermediate-risk patients for whom acute myocardial ischemia had been ruled out. The treating physicians were blinded to the ACI-TIPI scores, and patients underwent conventional evaluations including serial enzyme tests and provocative cardiac testing.

Among 400 patients who had ACI-TIPI scores of 20 or less, 265 were men younger than age 35 years or women younger than age 45 years, and 217 underwent provocative cardiac testing. None of the 265 patients developed an acute coronary syndrome within 30 days, as determined by phone calls to patients and reviews of records and the Social Security Death Index.

If clinicians had used an ACI-TIPI score of 20 or less in these subsets of young patients to exclude provocative cardiac testing and had sent these patients home, 15% of all stress tests in the study cohort could have been avoided without causing any harm, said Mr. Moyer-Diener, a medical student at the University of Michigan, Ann Arbor, who conducted the study with Michael G. Mikhail, M.D., and associates at the university.

At the meeting, physicians on a separate panel discussing cutting-edge research both praised and criticized the study.

“There's been a lot of debate about just how useful” an ACI-TIPI score is, said Charles V. Pollack Jr., M.D., chair of emergency medicine at Pennsylvania Hospital, Philadelphia. Many emergency physicians would rather not have a quantitative number related to the risk of ischemia on a patient's chart, he said, because if the case sparks a lawsuit, they would rather defend their clinical impression that the patient didn't have ischemia.

The ACI-TIPI was designed to predict the probability of cardiac ischemia on a 0− to 100-point scale, to serve as support or a “second opinion” in clinical decision making. The way ACI-TIPI was used in the study to identify patients who don't need further tests “is not really the use for which it was designed,” but the idea is intriguing, Dr. Pollack said.

Jerome R. Hoffman, M.D., lauded the investigators for trying to identify a strategy to cut down on the many unnecessary tests performed for chest pain evaluation that are not backed by evidence-based medicine. “It's very hard to get us out of that rut,” said Dr. Hoffman, professor of emergency medicine at the University of California, Los Angeles.

In practical terms, however, physicians are unlikely to adopt these criteria for avoiding stress tests. An ACI-TIPI score of 20 or less is associated with a 19% risk of acute myocardial ischemia, Dr. Hoffman explained. For medicolegal reasons, physicians will not feel comfortable sending patients home if that number appears on a patient's chart.

“That, more than anything, makes me question the value of an ACI-TIPI— other than as a research tool,” Dr. Hoffman said.

Previous studies have shown that physicians were from two to three times more likely to admit patients if given an ACI-TIPI score to include in the patient's chart, said Ian G. Stiell, M.D., of the University of Ottawa. On the other hand, it's “refreshing” to hear skepticism about widespread use in the United States of stress tests, chest pain units, and prolonged cardiac monitoring, he added.

Dr. Pollack noted that the current study claimed to exclude patients with acute myocardial ischemia. “I think that's a dangerous statement,” he said, “because ordinarily that is done in a chest pain center by measuring serial troponin levels, which excludes only necrosis. It doesn't exclude ischemia.”

SAN FRANCISCO — In some patients being evaluated for chest pain, stress tests might be avoided through the use of an algorithm designed to predict the probability of cardiac ischemia, David D. Moyer-Diener and his associates said at the annual meeting of the American College of Emergency Physicians.

In a prospective, observational cohort study of consecutive patients evaluated at a chest pain center, investigators obtained Acute Coronary Ischemia-Time Insensitive Predictive Instrument (ACI-TIPI) scores and conventional chest pain work-ups on 1,478 low- or intermediate-risk patients for whom acute myocardial ischemia had been ruled out. The treating physicians were blinded to the ACI-TIPI scores, and patients underwent conventional evaluations including serial enzyme tests and provocative cardiac testing.

Among 400 patients who had ACI-TIPI scores of 20 or less, 265 were men younger than age 35 years or women younger than age 45 years, and 217 underwent provocative cardiac testing. None of the 265 patients developed an acute coronary syndrome within 30 days, as determined by phone calls to patients and reviews of records and the Social Security Death Index.

If clinicians had used an ACI-TIPI score of 20 or less in these subsets of young patients to exclude provocative cardiac testing and had sent these patients home, 15% of all stress tests in the study cohort could have been avoided without causing any harm, said Mr. Moyer-Diener, a medical student at the University of Michigan, Ann Arbor, who conducted the study with Michael G. Mikhail, M.D., and associates at the university.

At the meeting, physicians on a separate panel discussing cutting-edge research both praised and criticized the study.

“There's been a lot of debate about just how useful” an ACI-TIPI score is, said Charles V. Pollack Jr., M.D., chair of emergency medicine at Pennsylvania Hospital, Philadelphia. Many emergency physicians would rather not have a quantitative number related to the risk of ischemia on a patient's chart, he said, because if the case sparks a lawsuit, they would rather defend their clinical impression that the patient didn't have ischemia.

The ACI-TIPI was designed to predict the probability of cardiac ischemia on a 0− to 100-point scale, to serve as support or a “second opinion” in clinical decision making. The way ACI-TIPI was used in the study to identify patients who don't need further tests “is not really the use for which it was designed,” but the idea is intriguing, Dr. Pollack said.

Jerome R. Hoffman, M.D., lauded the investigators for trying to identify a strategy to cut down on the many unnecessary tests performed for chest pain evaluation that are not backed by evidence-based medicine. “It's very hard to get us out of that rut,” said Dr. Hoffman, professor of emergency medicine at the University of California, Los Angeles.

In practical terms, however, physicians are unlikely to adopt these criteria for avoiding stress tests. An ACI-TIPI score of 20 or less is associated with a 19% risk of acute myocardial ischemia, Dr. Hoffman explained. For medicolegal reasons, physicians will not feel comfortable sending patients home if that number appears on a patient's chart.

“That, more than anything, makes me question the value of an ACI-TIPI— other than as a research tool,” Dr. Hoffman said.

Previous studies have shown that physicians were from two to three times more likely to admit patients if given an ACI-TIPI score to include in the patient's chart, said Ian G. Stiell, M.D., of the University of Ottawa. On the other hand, it's “refreshing” to hear skepticism about widespread use in the United States of stress tests, chest pain units, and prolonged cardiac monitoring, he added.

Dr. Pollack noted that the current study claimed to exclude patients with acute myocardial ischemia. “I think that's a dangerous statement,” he said, “because ordinarily that is done in a chest pain center by measuring serial troponin levels, which excludes only necrosis. It doesn't exclude ischemia.”

SAN FRANCISCO — In some patients being evaluated for chest pain, stress tests might be avoided through the use of an algorithm designed to predict the probability of cardiac ischemia, David D. Moyer-Diener and his associates said at the annual meeting of the American College of Emergency Physicians.

In a prospective, observational cohort study of consecutive patients evaluated at a chest pain center, investigators obtained Acute Coronary Ischemia-Time Insensitive Predictive Instrument (ACI-TIPI) scores and conventional chest pain work-ups on 1,478 low- or intermediate-risk patients for whom acute myocardial ischemia had been ruled out. The treating physicians were blinded to the ACI-TIPI scores, and patients underwent conventional evaluations including serial enzyme tests and provocative cardiac testing.

Among 400 patients who had ACI-TIPI scores of 20 or less, 265 were men younger than age 35 years or women younger than age 45 years, and 217 underwent provocative cardiac testing. None of the 265 patients developed an acute coronary syndrome within 30 days, as determined by phone calls to patients and reviews of records and the Social Security Death Index.

If clinicians had used an ACI-TIPI score of 20 or less in these subsets of young patients to exclude provocative cardiac testing and had sent these patients home, 15% of all stress tests in the study cohort could have been avoided without causing any harm, said Mr. Moyer-Diener, a medical student at the University of Michigan, Ann Arbor, who conducted the study with Michael G. Mikhail, M.D., and associates at the university.

At the meeting, physicians on a separate panel discussing cutting-edge research both praised and criticized the study.

“There's been a lot of debate about just how useful” an ACI-TIPI score is, said Charles V. Pollack Jr., M.D., chair of emergency medicine at Pennsylvania Hospital, Philadelphia. Many emergency physicians would rather not have a quantitative number related to the risk of ischemia on a patient's chart, he said, because if the case sparks a lawsuit, they would rather defend their clinical impression that the patient didn't have ischemia.

The ACI-TIPI was designed to predict the probability of cardiac ischemia on a 0− to 100-point scale, to serve as support or a “second opinion” in clinical decision making. The way ACI-TIPI was used in the study to identify patients who don't need further tests “is not really the use for which it was designed,” but the idea is intriguing, Dr. Pollack said.

Jerome R. Hoffman, M.D., lauded the investigators for trying to identify a strategy to cut down on the many unnecessary tests performed for chest pain evaluation that are not backed by evidence-based medicine. “It's very hard to get us out of that rut,” said Dr. Hoffman, professor of emergency medicine at the University of California, Los Angeles.

In practical terms, however, physicians are unlikely to adopt these criteria for avoiding stress tests. An ACI-TIPI score of 20 or less is associated with a 19% risk of acute myocardial ischemia, Dr. Hoffman explained. For medicolegal reasons, physicians will not feel comfortable sending patients home if that number appears on a patient's chart.

“That, more than anything, makes me question the value of an ACI-TIPI— other than as a research tool,” Dr. Hoffman said.

Previous studies have shown that physicians were from two to three times more likely to admit patients if given an ACI-TIPI score to include in the patient's chart, said Ian G. Stiell, M.D., of the University of Ottawa. On the other hand, it's “refreshing” to hear skepticism about widespread use in the United States of stress tests, chest pain units, and prolonged cardiac monitoring, he added.

Dr. Pollack noted that the current study claimed to exclude patients with acute myocardial ischemia. “I think that's a dangerous statement,” he said, “because ordinarily that is done in a chest pain center by measuring serial troponin levels, which excludes only necrosis. It doesn't exclude ischemia.”

The revelation in September that the popular arthritis drug rofecoxib (Vioxx) more than doubles the risk of myocardial infarction led to its withdrawal by Merck and to a reevaluation of the safety of other cyclooxygenase-2 inhibitors. In the aftermath, many have questioned why the Food and Drug Administration and Merck had not paid more attention to earlier results that also raised safety concerns.

Regardless of the conclusions reached by the various investigators, “More safety experience is going to be required, and there may be more cautionary labels not for what has been seen but for what is not known.

“The issues brought forth by Vioxx will ultimately drip down to almost everything we do. But we mustn't overlook the fact that a huge number of patients have taken the drug and been exposed to increased risk,” Barry Massie, M.D., chief of cardiology at the Veterans Affairs Medical Center, San Francisco, told CARDIOLOGY NEWS.

The revelation in September that the popular arthritis drug rofecoxib (Vioxx) more than doubles the risk of myocardial infarction led to its withdrawal by Merck and to a reevaluation of the safety of other cyclooxygenase-2 inhibitors. In the aftermath, many have questioned why the Food and Drug Administration and Merck had not paid more attention to earlier results that also raised safety concerns.

Regardless of the conclusions reached by the various investigators, “More safety experience is going to be required, and there may be more cautionary labels not for what has been seen but for what is not known.

“The issues brought forth by Vioxx will ultimately drip down to almost everything we do. But we mustn't overlook the fact that a huge number of patients have taken the drug and been exposed to increased risk,” Barry Massie, M.D., chief of cardiology at the Veterans Affairs Medical Center, San Francisco, told CARDIOLOGY NEWS.

The revelation in September that the popular arthritis drug rofecoxib (Vioxx) more than doubles the risk of myocardial infarction led to its withdrawal by Merck and to a reevaluation of the safety of other cyclooxygenase-2 inhibitors. In the aftermath, many have questioned why the Food and Drug Administration and Merck had not paid more attention to earlier results that also raised safety concerns.

Regardless of the conclusions reached by the various investigators, “More safety experience is going to be required, and there may be more cautionary labels not for what has been seen but for what is not known.

“The issues brought forth by Vioxx will ultimately drip down to almost everything we do. But we mustn't overlook the fact that a huge number of patients have taken the drug and been exposed to increased risk,” Barry Massie, M.D., chief of cardiology at the Veterans Affairs Medical Center, San Francisco, told CARDIOLOGY NEWS.

NEW ORLEANS — Antithrombotic treatment, in the form of the low-molecular-weight heparin reviparin, has been shown for the first time to safely improve the outcomes of patients with an acute MI.

“Although heparin is often routinely used to treat patients with an acute myocardial infarction, the incremental benefit from heparin or newer antithrombotics has been poorly defined,” Jeffrey L. Anderson, M.D., said at the annual scientific sessions of the American Heart Association.

The new findings show that reviparin “clearly improves the outcomes of patients who undergo thrombolysis with streptokinase or urokinase,” said Dr. Anderson, associate chief of the division of cardiology at LDS Hospital in Salt Lake City.

But the value of adding reviparin or a similar agent remains in doubt when patients are treated with the fibrin-specific drugs most often used for thrombolysis in the United States, such as alteplase (tissue plasminogen activator), reteplase, and tenecteplase. That's because this new trial, conducted in India, China, Pakistan, and several South American countries and involving 15,570 patients, included only about 100 patients treated with a fibrin-specific thrombolytic drug. Close to 80% of the patients received acute treatment to clear their coronary thrombus, but this treatment was primarily streptokinase in about 50% of patients, urokinase in about 23% of patients, and primary percutaneous intervention in about 6% of patients.

Despite this limitation, the results showed that “reviparin is a simple, inexpensive therapy that is globally applicable for treating acute myocardial infarction,” said Salim Yusuf, D.Phil., director of the division of cardiology at McMaster University in Hamilton, Canada, and lead investigator for the study.

Reviparin is marketed by Abbott Pharmaceuticals under the name Clivarine in several countries in Europe and Asia, but is not approved for U.S. use. Abbott provided the reviparin, but otherwise, the study had no commercial funding.

The study enrolled patients with ST-segment-elevation MI or new bundle branch block who presented within 12 hours of symptom onset. All patients were to be treated with aspirin, and they could also be treated with a regimen designed to produce reperfusion in their blocked coronary arteries. The average age of the patients was 59 years, and the average time from symptom onset to treatment was 4.8 hours, with 61% of patients treated within 6 hours. Aspirin was used on 97% of patients, 72% received an ACE inhibitor, 66% received a lipid-lowering drug, 60% received a β-blocker, and 55% received a thienopyridine, most commonly clopidogrel.

Patients were randomized to treatment with reviparin or placebo by subcutaneous injection b.i.d for 7 days; 76% of patients received the full 7-day course.

The study's primary end point was the incidence of death, repeat MI, or stroke during the 7 days of treatment. The rate of these outcomes was 11.0% in the placebo group and 9.6% in the reviparin group—a statistically significant relative reduction of 13%, Dr. Yusuf reported. Patients treated with reviparin also had a 13% relative reduction in the study's secondary end point, which included death, repeat MI, stroke, or ischemic ECG changes. Treatment with reviparin was also associated with a significant 11% relative reduction in death alone.

The protective effect from reviparin treatment extended to 30 days after the start of treatment. At that time, the rate of death, repeat MI, or stroke was 13.6% in the placebo group and 11.8% in the reviparin group, again a statistically significant 13% relative reduction. These results showed that “stopping therapy after 7 days was not associated with any rebound,” Dr. Yusuf said.

Like all antithrombotic drugs, reviparin boosted the rate of bleeding events. The rate of life-threatening or major bleeds not included in the primary outcomes after 7 days of treatment was 0.1% in the placebo group, compared with 0.2% in the reviparin group. The increased risk of important bleeding events was small, compared with the overall benefit, he noted.

Another noteworthy finding was that the faster treatment with reviparin started the greater the benefit. Patients who started treatment within 2 hours of symptom onset had a 30% relative drop in the primary end point. This relative benefit fell to 20% when treatment began 2–4 hours and to 15% when treatment began within 4–8 hours. The benefit completely disappeared when treatment was delayed beyond 8 hours.

An inevitable question is whether treatment with the low-molecular-weight heparins approved for use in the United States would confer the same benefits. “It's a tricky issue, because low-molecular-weight heparins are very heterogeneous compounds. You need to know the exact dosage to use.” Dr. Yusuf said.

NEW ORLEANS — Antithrombotic treatment, in the form of the low-molecular-weight heparin reviparin, has been shown for the first time to safely improve the outcomes of patients with an acute MI.

“Although heparin is often routinely used to treat patients with an acute myocardial infarction, the incremental benefit from heparin or newer antithrombotics has been poorly defined,” Jeffrey L. Anderson, M.D., said at the annual scientific sessions of the American Heart Association.

The new findings show that reviparin “clearly improves the outcomes of patients who undergo thrombolysis with streptokinase or urokinase,” said Dr. Anderson, associate chief of the division of cardiology at LDS Hospital in Salt Lake City.

But the value of adding reviparin or a similar agent remains in doubt when patients are treated with the fibrin-specific drugs most often used for thrombolysis in the United States, such as alteplase (tissue plasminogen activator), reteplase, and tenecteplase. That's because this new trial, conducted in India, China, Pakistan, and several South American countries and involving 15,570 patients, included only about 100 patients treated with a fibrin-specific thrombolytic drug. Close to 80% of the patients received acute treatment to clear their coronary thrombus, but this treatment was primarily streptokinase in about 50% of patients, urokinase in about 23% of patients, and primary percutaneous intervention in about 6% of patients.

Despite this limitation, the results showed that “reviparin is a simple, inexpensive therapy that is globally applicable for treating acute myocardial infarction,” said Salim Yusuf, D.Phil., director of the division of cardiology at McMaster University in Hamilton, Canada, and lead investigator for the study.

Reviparin is marketed by Abbott Pharmaceuticals under the name Clivarine in several countries in Europe and Asia, but is not approved for U.S. use. Abbott provided the reviparin, but otherwise, the study had no commercial funding.

The study enrolled patients with ST-segment-elevation MI or new bundle branch block who presented within 12 hours of symptom onset. All patients were to be treated with aspirin, and they could also be treated with a regimen designed to produce reperfusion in their blocked coronary arteries. The average age of the patients was 59 years, and the average time from symptom onset to treatment was 4.8 hours, with 61% of patients treated within 6 hours. Aspirin was used on 97% of patients, 72% received an ACE inhibitor, 66% received a lipid-lowering drug, 60% received a β-blocker, and 55% received a thienopyridine, most commonly clopidogrel.

Patients were randomized to treatment with reviparin or placebo by subcutaneous injection b.i.d for 7 days; 76% of patients received the full 7-day course.

The study's primary end point was the incidence of death, repeat MI, or stroke during the 7 days of treatment. The rate of these outcomes was 11.0% in the placebo group and 9.6% in the reviparin group—a statistically significant relative reduction of 13%, Dr. Yusuf reported. Patients treated with reviparin also had a 13% relative reduction in the study's secondary end point, which included death, repeat MI, stroke, or ischemic ECG changes. Treatment with reviparin was also associated with a significant 11% relative reduction in death alone.

The protective effect from reviparin treatment extended to 30 days after the start of treatment. At that time, the rate of death, repeat MI, or stroke was 13.6% in the placebo group and 11.8% in the reviparin group, again a statistically significant 13% relative reduction. These results showed that “stopping therapy after 7 days was not associated with any rebound,” Dr. Yusuf said.

Like all antithrombotic drugs, reviparin boosted the rate of bleeding events. The rate of life-threatening or major bleeds not included in the primary outcomes after 7 days of treatment was 0.1% in the placebo group, compared with 0.2% in the reviparin group. The increased risk of important bleeding events was small, compared with the overall benefit, he noted.

Another noteworthy finding was that the faster treatment with reviparin started the greater the benefit. Patients who started treatment within 2 hours of symptom onset had a 30% relative drop in the primary end point. This relative benefit fell to 20% when treatment began 2–4 hours and to 15% when treatment began within 4–8 hours. The benefit completely disappeared when treatment was delayed beyond 8 hours.

An inevitable question is whether treatment with the low-molecular-weight heparins approved for use in the United States would confer the same benefits. “It's a tricky issue, because low-molecular-weight heparins are very heterogeneous compounds. You need to know the exact dosage to use.” Dr. Yusuf said.

NEW ORLEANS — Antithrombotic treatment, in the form of the low-molecular-weight heparin reviparin, has been shown for the first time to safely improve the outcomes of patients with an acute MI.

“Although heparin is often routinely used to treat patients with an acute myocardial infarction, the incremental benefit from heparin or newer antithrombotics has been poorly defined,” Jeffrey L. Anderson, M.D., said at the annual scientific sessions of the American Heart Association.

The new findings show that reviparin “clearly improves the outcomes of patients who undergo thrombolysis with streptokinase or urokinase,” said Dr. Anderson, associate chief of the division of cardiology at LDS Hospital in Salt Lake City.

But the value of adding reviparin or a similar agent remains in doubt when patients are treated with the fibrin-specific drugs most often used for thrombolysis in the United States, such as alteplase (tissue plasminogen activator), reteplase, and tenecteplase. That's because this new trial, conducted in India, China, Pakistan, and several South American countries and involving 15,570 patients, included only about 100 patients treated with a fibrin-specific thrombolytic drug. Close to 80% of the patients received acute treatment to clear their coronary thrombus, but this treatment was primarily streptokinase in about 50% of patients, urokinase in about 23% of patients, and primary percutaneous intervention in about 6% of patients.

Despite this limitation, the results showed that “reviparin is a simple, inexpensive therapy that is globally applicable for treating acute myocardial infarction,” said Salim Yusuf, D.Phil., director of the division of cardiology at McMaster University in Hamilton, Canada, and lead investigator for the study.

Reviparin is marketed by Abbott Pharmaceuticals under the name Clivarine in several countries in Europe and Asia, but is not approved for U.S. use. Abbott provided the reviparin, but otherwise, the study had no commercial funding.

The study enrolled patients with ST-segment-elevation MI or new bundle branch block who presented within 12 hours of symptom onset. All patients were to be treated with aspirin, and they could also be treated with a regimen designed to produce reperfusion in their blocked coronary arteries. The average age of the patients was 59 years, and the average time from symptom onset to treatment was 4.8 hours, with 61% of patients treated within 6 hours. Aspirin was used on 97% of patients, 72% received an ACE inhibitor, 66% received a lipid-lowering drug, 60% received a β-blocker, and 55% received a thienopyridine, most commonly clopidogrel.

Patients were randomized to treatment with reviparin or placebo by subcutaneous injection b.i.d for 7 days; 76% of patients received the full 7-day course.

The study's primary end point was the incidence of death, repeat MI, or stroke during the 7 days of treatment. The rate of these outcomes was 11.0% in the placebo group and 9.6% in the reviparin group—a statistically significant relative reduction of 13%, Dr. Yusuf reported. Patients treated with reviparin also had a 13% relative reduction in the study's secondary end point, which included death, repeat MI, stroke, or ischemic ECG changes. Treatment with reviparin was also associated with a significant 11% relative reduction in death alone.

The protective effect from reviparin treatment extended to 30 days after the start of treatment. At that time, the rate of death, repeat MI, or stroke was 13.6% in the placebo group and 11.8% in the reviparin group, again a statistically significant 13% relative reduction. These results showed that “stopping therapy after 7 days was not associated with any rebound,” Dr. Yusuf said.

Like all antithrombotic drugs, reviparin boosted the rate of bleeding events. The rate of life-threatening or major bleeds not included in the primary outcomes after 7 days of treatment was 0.1% in the placebo group, compared with 0.2% in the reviparin group. The increased risk of important bleeding events was small, compared with the overall benefit, he noted.

Another noteworthy finding was that the faster treatment with reviparin started the greater the benefit. Patients who started treatment within 2 hours of symptom onset had a 30% relative drop in the primary end point. This relative benefit fell to 20% when treatment began 2–4 hours and to 15% when treatment began within 4–8 hours. The benefit completely disappeared when treatment was delayed beyond 8 hours.

An inevitable question is whether treatment with the low-molecular-weight heparins approved for use in the United States would confer the same benefits. “It's a tricky issue, because low-molecular-weight heparins are very heterogeneous compounds. You need to know the exact dosage to use.” Dr. Yusuf said.