Serum carboxy-terminal propeptide of procollagen type I is a marker of myocardial fibrosis in hypertensive heart disease.

BACKGROUND: This study was designed to investigate whether the serum concentration of the carboxy-terminal propeptide of procollagen type I (PIP), a marker of collagen type I synthesis, is related to myocardial fibrosis in hypertensive patients. METHODS AND RESULTS: The study was performed in 26 patients with essential hypertension in which ischemic cardiomyopathy was excluded after a complete medical workup. Right septal endomyocardial biopsies were performed in hypertensive patients to quantify collagen content. Collagen volume fraction (CVF) was determined on picrosirius red-stained sections with an automated image analysis system. The serum concentration of PIP was measured by specific radioimmunoassay. Compared with normotensives, both serum PIP and CVF were increased (P<0.001) in hypertensives. A direct correlation was found between CVF and serum PIP (r=0.471, P<0.02) in all hypertensives. Histological analysis revealed the presence of 2 subgroups of patients: 8 with severe fibrosis and 18 with nonsevere fibrosis. Serum PIP was higher (P<0.05) in patients with severe fibrosis than in patients with nonsevere fibrosis. Using receiver operating characteristic curves, we observed that a cutoff of 127 microg/L for PIP provided 78% specificity and 75% sensitivity for predicting severe fibrosis with a relative risk of 4.80 (95% CI, 1.19 to 19.30). CONCLUSIONS: These results show a strong correlation between myocardial collagen content and the serum concentration of PIP in essential hypertension. Although preliminary, these findings suggest that the determination of PIP may be an easy and reliable method for the screening and diagnosis of severe myocardial fibrosis associated with arterial hypertension.

Prevalence and significance of hepatitis C viremia in chronic active hepatitis B.

OBJECTIVES: To assess the prevalence and significance of HCV infection in patients with chronic active hepatitis B. METHODS: We studied clinical and histological activity in 132 patients with chronic active hepatitis B, 17 of whom were co-infected by HCV. Serum HBV-DNA was determined by dot-blot hybridization and polymerase chain reaction (PCR) and serum HCV-RNA was determined by ELISA-2, RIBA-2, and reverse transcription PCR (RT-PCR). RESULTS: HBV-DNA was detected by dot-blot in five of 17 (29.4%) patients in the HCV-RNA-positive group and in 64 of 115 (55.6%) in the HCV-RNA-negative group (p < 0.05). The low levels of HBV replication (assessed by PCR) were similar in both groups. Mean levels of serum AST, ALT, and gamma-globulin, as well as mean scores of liver damage, were significantly higher among HCV-RNA-positive patients than among HCV-RNA-negative patients. CONCLUSIONS: 1) Concomitant HCV infection occurs frequently in patients with chronic active hepatitis B; 2) co-infection of HBV and HCV is more common in the absence of HBV-DNA detected by dot-blot hybridization; 3) liver disease seems to be more severe in patients with concomitant HBV and HCV infection, even though the number of replicative HBV patients was lower in the group of HCV-infected patients. This suggests that the role of HCV is probably important as the cause of persistent liver disease. 4) The detection of HBV-DNA by dot-blot and HCV-RNA by PCR could help to establish whether HBV, HCV, or both contribute to liver injury.

[Influence of hepatitis C virus infection and human immunodeficiency on the natural history of chronic delta hepatitis]. / Influencia de la infección por los virus de la hepatitis C y de la inmunodeficiencia humana en la historia natural de la hepatitis crónica delta.

OBJECTIVES: To analyze the prevalence and clinical significance of HCV an HIV infections among a group of patients with chronic delta hepatitis. METHODS: We have studied the clinical and the histological activity and the serological profile the HBV DNA was analyzed by dot blot and PCR and the HDV RNA by dot blot) in 46 patients with chronic delta hepatitis. These results were correlated with HCV infection (assessed by ELISA-2, RIBA-2 and RT-PCR) and HIV infection (ELISA and immunoblot). RESULTS: HBV DNA and HDV RNA was detected by dot in 28.2% and 71.4% of patients respectively, and by PCR, 89.1% of patients had HBV DNA in their serum. Twenty two of 46 patients with chronic delta hepatitis were anti-HCV positives (with HCV RNA detectable in sera by RT-PCR in 19 cases). Anti-HIV positivity was detected in 19 of 46 patients. The mean aminotransferase level, histological activity and serological profile was similar in the anti-HCV positive and negative patients. Likewise, clinical and histological activity and serological profile was similar in the anti-HIV positive and negative patients. CONCLUSIONS: Concomitant infection with HCV or HIV does not seem to significantly modify the clinical course of chronic delta hepatitis. In addition, no significant serological difference has been noted in patients with chronic delta hepatitis with anti-HIV or anti-HCV antibodies.

Early primary tissue failure of a Labcor bioprosthesis.

A 78-year-old woman underwent re-replacement of a 19mm Labcor bioprosthesis implanted in aortic position eighteen months earlier. The rupture of the free margin of one leaflet was found at reoperation. There was no apparent cause of this rupture.

Acute hepatitis by Listeria monocytogenes in an HIV patient with chronic HBV hepatitis.

We report a young male IVDA with CAH caused by HBV who was infected with HIV and who contracted listeriosis in the form of acute hepatitis and bacteremia, with epithelioid granulomas in the liver. Treatment with ampicillin and a aminoglycoside for 3 weeks was followed by rapid and maintained improvement. Involvement of the liver is unusual in listeriosis and, as far as we are aware, it has not been described previously in patients with HIV infection.

In vivo experimental assessment of polytetrafluoroethylene trileaflet heart valve prosthesis.

This report summarizes the results of a series of experimental implantations of polytetrafluoroethylene valves in sheep. Twelve prostheses were implanted in the tricuspid position in weanling (3- to 4-month-old, 26 +/- 3 kg) sheep. The valve sizes were 23 mm (eight animals) and 25 mm (four animals). There were two early deaths, and the 10 survivors were killed in a stepwise manner to get a mineralization profile of the valve. There was one episode of acute thrombosis but no evidence of pulmonary thromboemboli in any animal. In all cases the leaflets were thin and unretracted, but in half of them one cusp or more were stiffened. One valve displayed a fixed outward eversion of the free margin of two leaflets. Macroscopic calcification was detected in seven specimens and always involved the commissural areas. Radiologic studies confirmed this calcium topography and revealed only one case of severe and diffuse mineralization. In most cases the cusps showed a grossly visible pannus that was thinner and less extensive than usually seen in bioprostheses. Examination with light microscopy disclosed a complete lack of infiltrating cells within the cuspal material (made of compact polytetrafluoroethylene). However, those parts of the prostheses made of expanded polytetrafluoroethylene (the material covering the valve frame and the sutures) did show infiltration by host cells and calcium. Mineralized lesions were of extrinsic type, involving fibrin and fibroelastic host tissue accumulated in the inflow aspect of the commissures. Examination with transmission electron microscopy disclosed electron-dense masses surrounded by an electron-lucent granular homogeneous material in areas of mineralization. The time-course evolution of the tissue calcium content shows a moderate mineralization rate (0.46 +/- 0.31 mg/gm of dry-weight material per week of follow-up) and a marginally significant positive correlation between calcium content and follow-up. Our results suggest that the polytetrafluoroethylene valves have a moderate overall calcification rate and that calcium deposits appear to be always related to the commissural region and to the presence of expanded polytetrafluoroethylene.

Degenerative pathologic findings after long-term implantation of bovine pericardial bioprosthetic heart valves.

Degeneration of bioprosthetic heart valves constitutes the most important limitation to their long-term durability and the factor that avoids a wider clinical use of these devices. We studied 26 degenerated bovine pericardial valves that belong to a series of 55 prostheses explanted for various reasons. Age of the patients at implantation of the valve and other factors predisposing to primary tissue failure did not seem to significantly influence the results obtained. Mean implantation time was longer for aortic than for mitral valves (p less than 0.05). Also, the mode of failure was different for mitral and aortic prostheses. Tearing of one or more leaflets without mineralization was more frequent (p less than 0.0025) among mitral than among aortic specimens. Coverage of the valve cusps by a macroscopically visible host sheath was more extensive on the outflow than on the inflow aspect (p less than 0.0015 aortic valves; p less than 0.015 mitral valves). On radiological examination the majority of valves had diffuse and severe mineralized lesions. Collagen degeneration was the most frequent histologic lesion to be found in both mineralized and calcium-free valves. Calcification was also frequent and appeared as mineral deposits that extended between different collagen planes. Scanning electron microscopy revealed the almost complete lack of "endothelium-like" cover on any of the valves and exposure of the underlying fibrous components of the pericardial tissue in areas subjected to abrasion. Transmission electron microscopy confirmed the collagen degeneration and disclosed electron-dense microparticles (probably mineralized) both in the extracellular space and within degenerated host connective tissue cells.

Comparative study of primary tissue failure between porcine (Hancock and Carpentier-Edwards) and bovine pericardial (Ionescu-Shiley) bioprostheses in the aortic position at five- to nine-year follow-up.

Retrospective follow-up data on 458 consecutive patients who received a Hancock, Carpentier-Edwards (C-E) or Ionescu-Shiley (I-S) bioprosthesis in the aortic valve position between April 1978 and December 1981 are reviewed. A total of 461 valves (184 Hancock, 131 C-E and 146 I-S) were available for study of the incidence of primary tissue valve failure after 5 to 9 years of follow-up. Cumulative follow-up was 1,016 patient-years for patients with Hancock valve, 688 for the C-E and 767 for the I-S group. Of the 397 prostheses at risk (154 Hancock, 120 C-E and 123 I-S), 36 instances of primary tissue valve failure occurred (12 Hancock, 7 C-E and 17 I-S). On an actuarial basis, the calculated probability of freedom from primary tissue valve failure was 88 +/- 4% for the Hancock group, 87 +/- 6% for the C-E and 51 +/- 17% for the I-S at 9 years. The linear incidence of tissue valve failure was 1.2 failing valves per 100 patient-years for the Hancock group, 1 for the C-E and 2.2 for the I-S. In a cohort of patients older than 40 years of age at the time of valve replacement, the rate of freedom from primary failure was 98 +/- 1%, 87 +/- 9% and 44 +/- 22% for the Hancock, C-E and I-S groups, respectively, at 9 years. Comparison of actuarial curves disclosed a meaningful difference between the pericardial valve and the Hancock and C-E porcine bioprostheses at 9-year follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term performance of porcine heart valve bioprostheses.

To assess the results after long-term implantation of porcine bioprosthetic heart valves, 320 patients with 381 valves were retrospectively reviewed. This group included all patients receiving one such xenograft in the mitral or aortic position (or both) in our institution between June 1974 and December 1976. The patients had a follow-up of 9-11.5 years. Actuarial patient survival rats (hospital mortality excluded) were 85%-90% at 6 years and 68%-79% at 11.5 years. Thromboembolic episodes did not show any significant clustering over the first weeks or months, in fact, they appeared at a constant rate. Actuarial rates of freedom from thromboembolism were greater than 90% for aortic patients at 11.5 years and greater than 80% for mitral and mitroaortic patients at 11.5 years. The linearized rate of anticoagulant-related haemorrhage for the whole group of patients was 0.4 events/100 patient years with a related mortality of 0.2 events/100 patient years. Prosthetic valve endocarditis and paravalvular leak appeared at linearized rates of 0.6 (0.1 of related mortality) and 0.4 (0.1 of related mortality) events/100 patient years. Primary tissue valve failure constituted the most prevalent complication (82 cases) in the long term but did not significantly worsen patient survival. Actuarial rates of freedom from primary tissue failure were 91% +/- 2% at 6, and 40% +/- 14% at 11.5 years for mitral valves, and 95% +/- 4% at 6 and 64% +/- 6% at 11.5 years for aortic valves.(ABSTRACT TRUNCATED AT 250 WORDS)

Incidence of primary tissue valve failure in porcine bioprosthetic heart valves.

This report provides retrospective follow-up data on 324 consecutive patients who received a Hancock-I porcine valve in the aortic or the mitral position, or in both positions, between June, 1974, and December, 1976. This analysis included 319 valves (193 mitral, 126 aortic) available for study of the incidence of primary tissue valve failure after 10 to 12.5 years of follow-up. Of the 319 prostheses at risk, 114 instances of primary tissue valve failure occurred. Seventy-three of the failed valves were in the mitral position, and 41 were in the aortic position. The calculated actuarial probability of freedom from primary tissue valve failure was 52 +/- 5% for the mitral and 58 +/- 6% for the aortic prostheses at 12.5 years of follow-up. For patients older than 40 years at the time of operation, the rate of freedom from primary failure was 68 +/- 8% and 55 +/- 6% for aortic and mitral prostheses, respectively, at 12.5 years. Comparison of both actuarial curves disclosed no meaningful difference. However, a tendency toward greater failure rate was observed in the mitral prosthesis group.

The behavior of pericardial versus porcine valve xenografts in the growing sheep model.

The comparative long-term behavior of the pericardial versus the porcine bioprostheses is not yet known. The need for long follow-up times to answer this question makes the growing sheep model an attractive alternative, given its ability to induce early valve degeneration. Sixty-three sheep, 12 to 16 weeks old, were operated on and received 39 porcine (11 Xenomedica, 10 Carpentier-Edwards S, nine Hancock I standard, and nine Hancock I T6-treated) and 24 pericardial (14 Mitroflow and 10 Ionescu-Shiley low profile) prostheses of clinical quality in the tricuspid position. Of the 52 operative survivors (32 received porcine valves and 20 received pericardial bioprostheses), six animals (five pericardial and one porcine) were eliminated because of bioprosthetic infection. Late sudden death before the scheduled killing occurred significantly more often (p less than 0.0001) in the pericardial (8/15 or 53%) than in the porcine group (1/31 or 3%). Calcium content of the explanted valves was significantly correlated with time in the pericardial group and the Xenomedica porcine prostheses (p less than 0.05) but not in the Hancock I and Carpentier-Edwards S valves, where it was only marginally significant (0.1 greater than p greater than 0.05). Linear regression analysis of tissue calcium content showed a similar slope for the pericardial group and Xenomedica porcine valves, in comparison with the remaining porcine valves. Comparison between the two lines using covariance analysis demonstrated a statistically significant difference between them, which shows that the pericardial and Xenomedica porcine valves appear to reach higher levels of calcification in a shorter follow-up time than the Hancock I, standard and T6-treated, and the Carpentier-Edwards S valve in this animal model.

Primary tissue valve degeneration in glutaraldehyde-preserved porcine bioprostheses: Hancock I versus Carpentier-Edwards at 4- to 7-years' follow-up.

In the 32-month period between April, 1978, and December, 1980, 292 patients, divided into two equal groups, received a glutaraldehyde porcine bioprosthesis--either Hancock or Carpentier-Edwards (CE)--as mitral valve substitute. Every patient receiving a mitral porcine xenograft during that time was included in the study. The type of bioprosthesis was always selected by the surgeon and not randomly. Preoperative clinical characteristics, associated surgical procedures, valve implantation sizes, and follow-up data showed no relevant differences between the two groups. There were three instances of primary tissue failure in the Hancock group and six in the CE (linearized rates of 0.49 and 0.97 events percentage of patient/years, respectively). Mean duration of explanted valves and microscopic findings were similar in both groups. Primary tissue failure was more frequent in patients under 40 years of age in both groups, although differences were not statistically significant. A marginally significant trend toward greater incidence of tissue failure in patients of 40 years of age and older was seen in the CE group when compared with the Hancock group. Actuarial survival of the bioprostheses free from primary tissue failure was 6.5 years of 95 +/- 3% (mean +/- standard error) for Hancock and 84 +/- 9% for CE (p = NS). No significant difference in terms of durability has been found between the two most popular glutaraldehyde porcine bioprostheses, although the behavior of the CE in patients older than 40 years should be reassessed in a study with a larger number of patients and a longer follow-up period.

Could alpha 1 antitrypsin deficiency have any role in the development of celiac sprue after gastric operations?

We report a 50-year-old woman with alpha 1 antitrypsin deficiency (PiSZ phenotype) who developed clinical features of malabsorption after vagotomy and pyloroplasty. The intestinal biopsy demonstrated total villous atrophy with hypertrophy of the crypts. After gluten withdrawal, digestive function and the appearance of the intestinal biopsy returned to normal. We raise the possibility of an association between alpha 1 antitrypsin deficiency and celiac sprue.

Six- to ten-year follow-up of patients with the Hancock cardiac bioprosthesis. Incidence of primary tissue valve failure.

From June, 1974, through June, 1978, 547 porcine xenografts (299 mitral, 239 aortic, eight tricuspid, and one pulmonary) were inserted in 459 selected patients who survived the operation and were considered at risk for primary tissue valve failure. Ninety-two instances of primary tissue valve degeneration occurred in 82 of the 459 patients. In patients operated on 10 years ago, 28% of the valves implanted in the mitral position (5/18) and 33% in the aortic position (4/12) failed. These percentages decreased to 24% (21/89) and 26% (15/57) for those implanted in 1975, 15% (13/85) and 16% (9/57) for those implanted in 1976, 13% (9/71) and 15% (12/82) for 1977, and 8% (3/36) and 3% (1/31) for 1978. None of the tricuspid or pulmonary valves have failed. The rate of valve survival without primary degeneration was 70% +/- 6% for the mitral and 69% +/- 7% for the aortic prostheses at 10 years of follow-up. Of the 10 valves implanted in patients younger than 20 years of age, 40% of the mitral and 60% of the aortic valves failed. This rate is 26% for mitral and 42% for aortic for the 21 to 30 year group, 20% and 19% for 31 to 40 years, 9% and 13% for 41 to 50 years, 20% and 6% for 51 to 60 years, and 11% and 0% for 61 to 70 years. The average interval between placement and explantation or death was 74 months (range 10 to 112) for valves in the mitral position and 78 months (range 13 to 117) for valves in the aortic position. We believe these current data should have some bearing of practical import not only when comparing different types of bioprostheses but especially when recommending the appropriate valve replacement for the individual patient.

Comparative study of primary tissue valve failure between Ionescu-Shiley pericardial and Hancock porcine valves in the aortic position.

From August 1977 to June 1981, 221 patients received a Hancock porcine valve and 133 an Ionescu-Shiley bovine (I-S) pericardial valve as aortic valve substitutes. No special selection or randomization was used and no patient with either of these types of valves was excluded. Preoperative data show no differences between the groups influencing the appearance of primary tissue failure. Hospital survivors were followed until June 1984 and those with an uneventful history at least 36 months. Patients who died late postoperatively or who underwent reoperation for causes other than primary dysfunction were considered at risk until death or reoperation. Primary tissue failure occurred in 8 patients in the I-S group from 36 to 70 months postoperatively and in 6 patients of the Hancock group from 24 to 83 months. Linearized rates of primary failure were 0.61 valves per 100 patient-years for the Hancock and 1.70 valves per 100 patient-years for the I-S group. Mean age of patients with failing valves was 38 years (range 25 to 55) for Hancock valves and 39 years (range 15 to 62) for I-S valves. Actuarial analysis shows a lower rate of primary dysfunction in the Hancock group since the fourth year, which is statistically significant in the sixth and seventh years (96.5 +/- 1.5% vs 79.6 +/- 7.6% in the sixth year and 93.1 +/- 3.6 vs 79.6 +/- 7.6% in the seventh year). Microscopically, calcium and collagen degeneration were consistently associated and present on failing bioprostheses.(ABSTRACT TRUNCATED AT 250 WORDS)

Four- to seven-year follow-up of patients undergoing Carpentier-Edwards porcine heart valve replacement.

From April 1978 through December 1980, 216 Carpentier porcine xenografts (144 mitral, and 72 aortic) were inserted in 189 patients (117 mitral, 45 aortic, and 27 mitral and aortic). The hospital mortality was 8.5% (10/117) for mitral patients, 6.6% (3/45) for aortic, and 3.8% (1/27) for mitral and aortic. Of 175 patients discharged from the hospital, there were 16 late deaths, which represents an incidence of 1.9% per patient-year (10/107) for mitral, 0.9% per patient-year (2/42) for aortic, and 3.4% per patient-year (4/26) for mitral and aortic, patients. There were 13 thromboembolic events in 10 patients. This represents a linearized incidence of 2.3%, and 0.5% per patient-year for mitral and aortic patients, respectively. One of the accidents was fatal, and 3 of the 10 patients were on a regimen of anticoagulation at the time of embolism. Seven instances of valve endocarditis occurred in 4 mitral, 1 aortic, and 2 mitral and aortic patients (5 mitral, 2 aortic, and 2 mitral and aortic). This represents a linearized incidence of primary tissue failure of 0.96%, 0.96% and 1.7% per patient-year for mitral, aortic, and mitral and aortic patients, respectively.