Caroline J. Doré

Tricuspid valve replacement: UK heart valve registry mid-term results comparing mechanical and biological prostheses

BACKGROUNDnLittle is known of time-related outcome and comparative performance of biological and mechanical prostheses following tricuspid valve replacement (TVR).nnnMETHODSnA retrospective UK Heart Valve Registry study (Jan 1, 1986 to June 30, 1997) identified 425 patients who underwent TVR. Two-hundred twenty-five (52.9%) received biological and 200 (47.1%) received mechanical valves. One-hundred sixty (38%), 158, and 76 had isolated, double, and triple valve replacements, respectively. The follow-up was 96% complete with a total of 1,585 patient-years.nnnRESULTSnThirty-day mortality for TVR was 17.3% (73 deaths). One-, 5-, and 10-year survival rates were 72.2%, 59.9%, and 42.9%, respectively. Year of operation (p = 0.04), age (p = 0.04), and number of valves implanted (p = 0.0 3) predicted overall mortality. Age (p<0.001) and year of operation (p = 0.002) predicted overall survival. Thirty-day mortality for biological and mechanical prostheses was 18.8% and 15.6%, respectively. One-, 5-, and 10-year survival rates were 70.5%, 61.5%, and 47.7% for biological and 74.0%, 57.9%, and 33.9% for mechanical prostheses, respectively. Freedom from reoperation at 1 and 10 years was 98.7% and 97.4%. Freedom from death or reoperation was 71.2% at 1 year and 41.9% at 10 years. None of the above outcomes was significantly different between the type of valve prostheses.nnnCONCLUSIONSnTVR carries a high 30-day mortality and a poor longer term survival. No superiority could be identified for biological or mechanical prostheses in the tricuspid position for either survival or reoperation.

Effect of Image Normalization on Carotid Plaque Classification and the Risk of Ipsilateral Hemispheric Ischemic Events: Results from the Asymptomatic Carotid Stenosis and Risk of Stroke Study:

The aim of this study was to determine the effect of image normalization on plaque classification and the risk of ipsilateral ischemic neurologic events in patients with asymptomatic carotid stenosis. The first 1,115 patients recruited to the Asymptomatic Carotid Stenosis and Risk of Stroke (ACSRS) study with a follow-up of 6 to 84 months (mean 37.1 months) were included in this study. Duplex ultrasonography was used for grading the degree of internal carotid artery stenosis and for plaque characterization (types 1–5), which was performed before and after image normalization. One hundred sixteen ipsilateral ischemic hemispheric events occurred. Image normalization resulted in 60% of plaques being reclassified. Before image normalization, a high event rate was associated with all types of plaque. After image normalization, 109 (94%) of the events occurred in patients with plaque types 1 to 3. For patients with European Carotid Stenosis Trial (ECST) 70 to 99% diameter stenosis (equivalent to North American Symptomatic Carotid Endarterectomy Trial [NASCET] 50–99%) with plaque types 1 to 3, the cumulative stroke rate was 14% at 7 years (2% per year), and for patients with plaque types 4 and 5, the cumulative stroke rate was 0.9% at 7 years (0.14% per year). The results suggest that asymptomatic patients with plaque types 4 and 5 classified as such after image normalization are at low risk irrespective of the degree of stenosis.

Thirty-day mortality and long-term survival following surgery for prosthetic endocarditis: a study from the UK heart valve registry

OBJECTIVEnTo assess the 30-day mortality, long-term survival and freedom from reoperation following surgery for prosthetic endocarditis (PVE).nnnMETHODnA retrospective analysis of data from the UK Heart Valve Registry of 322 patients who had undergone single mechanical/bioprosthetic valve replacement for PVE between 1 January 1986 and 31 December 1996. The mean age was 54.9 +/- 12.8 years and 213 (66.1%) were males. There were 170 aortic and 152 mitral valve implantations. Eighty-five (26%) of the infected valves were bioprosthetic and 237 (74%) were mechanical. Of the new prostheses implanted 53 (17%) were bioprosthetic and 269 (83%) were mechanical. Of those with infected bioprostheses, 50 (15.2%) had mechanical valves at redo surgery, whilst 219 (68.3%) of infected mechanical prostheses were re-replaced by mechanical prostheses. The follow-up was 98% complete with a total of 1084.9 patient years.nnnRESULTSnThe 30-day mortality was 63 (19.9%; 95%CI 15.9-24.7%). There were 85 late deaths. One, 5 and 10 year survival rates were 67.1% (61.6-72.0%), 55.0% (49.0-60.7%) and 37.6% (27.9-47.2%), respectively. Age was the only significant determinant of 30-day mortality (P = 0.04). Age (P = 0.001) and explanting of infected bioprosthesis and replacement by mechanical valve (P = 0.04) determined long-term survival (P = 0.001). The incidence of re-reoperation was 9.9%. Freedom from reoperation for PVE was 88.4, 87.3 and 87.3% at 1, 5 and 10 years, respectively. Explanting of bioprosthesis and replacement by mechanical valve (P < 0.001) and reoperation within 60 days of native valve replacement (P = 0.02) were determinants of reoperation for PVE. Freedom from death or reoperation was 61.1, 50.6 and 34.2% at 1, 5 and 10 years, respectively. Age (P = 0.003), explanting of bioprosthesis and replacement by mechanical valve (P = 0.002) and the period between prosthetic re-replacement (P = 0.04) determined freedom from death or reoperation.nnnCONCLUSIONnOperation for PVE carries a high 30-day mortality and reduced long-term survival. There is no evidence that type of prosthesis used for re-reoperation determines survival or freedom from re-reoperation.

Juxtaluminal hypoechoic area in ultrasonic images of carotid plaques and hemispheric symptoms

OBJECTIVESnThe aim was to determine the diagnostic value of a juxtaluminal black (hypoechoic) area without a visible echogenic cap (JBA) in ultrasonic images of internal carotid artery plaques.nnnMETHODSnUltrasonic images of plaques from 324 patients with asymptomatic (n = 139) and symptomatic (n = 185) internal carotid 50% to 99% stenosis in relation to the bulb (European Carotid Surgery Trial) referred for duplex scanning were studied. The JBA in mm(2) and the gray-scale median (GSM) were obtained after image normalization. Cut-off points for GSM and JBA (combined highest sensitivity with highest specificity) were determined from receiver operator characteristic (ROC) curves.nnnRESULTSnJBA >or= 8 mm(2) was associated with a high prevalence of symptomatic plaques in all grades of stenosis. In a multiple logistic regression model, increasing stenosis (mild, moderate, severe), GSM <or= 15 and JBA >or= 8 mm(2) were independent predictors of the presence of hemispheric symptoms. This model could identify a high-risk group of 188 plaques that contained 142 (77%) of the 185 symptomatic plaques (odds ratio [OR], 6.7; 95% confidence interval [CI], 4.08-10.91), (P < .001), (sensitivity: 77%; specificity 66%; positive predictive value 75%; negative predictive value 68%).nnnCONCLUSIONSnThe results of this study indicate the diagnostic value and for the first time suggest a cut-off point of 8 mm(2) for JBA. This cut-off point needs to be validated in other groups and then applied to prospective studies of asymptomatic patients.

Carotid and femoral arterial wall changes and the prevalence of clinical cardiovascular disease

Abstract The Cyprus Study is a prospective cohort study of cardiovascular disease (CVD). Its aim is to determine the relationship of intima–media thickness (IMT) of the common carotid (IMTcc), maximum thickness of IMT in the carotid bifurcation (IMTmax), number of carotid and femoral bifurcations with plaque and total plaque thickness (TPT) (sum of the maximum plaque measurements taken from the four bifurcations scanned) with the prevalence of clinical CVD. A total of 767 individuals (46% male) over the age of 40 years were recruited from a mountain village and a town outside the capital Nicosia. In addition to clinical examination, carotid and common femoral bifurcations were scanned with ultrasound. After controlling for conventional risk factors, there was little evidence of an association of IMTcc with CVD prevalence. However, IMTmax and TPT were associated with 2.9-fold (1.22 to 7.07) and 6.87-fold (2.42 to 19.43) increased odds of CVD prevalence, respectively. In conclusion, the TPT and number of bifurcations with plaque are more strongly associated with the prevalence of CVD. These findings warrant investigation in prospective studies to document associations with incident CVD events.

Postural variation in intraocular pressure in primary chronic autonomic failure

Abstract. Patients with syndromes of generalised autonomic failure often have extreme posture-related lability of blood pressure, with both orthostatic hypotension and recumbent hypertension. Whether these changes influence intraocular pressure (IOP) is not known. Mean arterial pressure (MAP) and IOP were measured in response to variations in posture between +45° and −20° in 8 normal subjects and 9 subjects with primary generalised chronic autonomic failure (AF). With postural change normal subjects showed minimal change in MAP (p=0.6) and small but significant changes in IOP (p < 0.001). Subjects with AF showed large and significant changes in both MAP (p < 0.001) and IOP (p < 0.001). Two AF subjects had raised IOP when recumbent, despite normal IOP at +45°. There was significant covariance of MAP and IOP (p < 0.001 overall, p=0.004 in normal subjects, p=0.006 in AF subjects). However, individually, those patients with large changes in IOP could not be predicted from changes in MAP. These data show that patients with autonomic failure are subject to large posture-related changes in IOP. These appear to be related to the large posture-induced changes in systemic blood pressure which occur in these patients.

Inhaled nitric oxide in premature neonates

Sir—John Kinsella and colleagues and the Franco-Belgium Collaborative NO Trial Group (Sept 25) report randomised trials involving inhaled nitric oxide (NO) in neonatal respiratory failure. Surprisingly, Ola Saugstad’s otherwise admirable commentary fails to draw attention to important methodological concerns. In Kinsella and colleagues’ trial, the primary outcome measure was mortality. Sample-size calculations were based on an assumed mortality of 50% in the control group. The investigators state that a sample size of 105 infants in each group was required to detect a 30% decrease in mortality at the 5% significance level with 80% power. In fact, 105 infants in each group would detect a reduction in mortality from 50% to 30%, ie, by 40% not 30% (or improvement in survival by 40% from 50% to 70%). That this was a realistic expectation of treatment effect is questionable. A smaller improvement in survival to 60% would also be clinically important and probably more realistic, but this would have required the enrolment of 408 infants into each group. Unfortunately, the problem was worsened because the trial was closed early after only 80 of the planned 210 infants had been enrolled. The investigators justify this because, “projections suggested that detection of differences was unlikely”. In fact, the relative risk for survival in the treated group was 1·11 (95% CI 0·7–1·8), so the results of this trial were compatible with a 30% reduction in survival to a 80% increase in survival, which includes a 40% improvement. Sample-size calculations for the Franco-Belgium study required a total of 360 infants for 80% power to detect a decrease in oxygenation index of at least 33% at 2 h. The clinical relevance of this outcome measure is questionable. The trial was stopped after the recruitment of only 192 infants. Further, in the analysis infants were stratified by gestational age (<33 weeks, 33 weeks) and comparisons are only made within each strata and not for the group as a whole. Much is made of the fact that a significant treatment effect was detected only in near-term infants, but there were more infants in this stratum (107 vs 85), and the magnitude of the treatment effect was similar in both strata. Non-parametric analyses were used, so it is not possible to estimate an overall treatment effect or test for an interaction between treatment and strata with the summary measures shown. Saugstad alludes to “lack of beneficial effect” of inhaled NO in preterm infants. The regrettable truth is that despite 272 newborn infants and their parents having been through the rigours of a randomised controlled trial, little advance to our knowledge has been achieved. Methodological errors, including inappropriate outcome measures, unrealistic expectations of the magnitude of the treatment effect, and premature, unjustifiable trial closure have resulted in neither a positive nor a negative outcome.

Validation of endobronchial biopsy specimens for nerve quantitation by computer-assisted image analysis

The aim of this study was to assess the validity of endoscopic bronchial biopsy specimens for the quantitation of nerves. To this end, endobronchial biopsy was simulated ex vivo on surgically resected lung specimens and nerve densities were compared in airway smooth muscle of biopsy and surrounding tissue. Specimens were stained immunohistochemically for the general neural marker protein gene product 9.5 (PGP 9.5) and for vasoactive intestinal peptide (VIP), and nerve densities were quantitated using computer‐assisted image analysis. Nerve density for total (PGP 9.5‐immunoreactive) nerves was slightly higher in biopsies than in corresponding lung tissue, but this difference did not reach statistical significance (p=0.08). There was also no significant difference in the density of VIP‐immunoreactive nerves (p=0.60). These findings support the use of endobronchial biopsy specimens to quantitate nerves in asthma and other airway diseases. Copyright

Randomised double-blind trial of combination antibiotic therapy in rheumatoid arthritis.

Objective. A combination of intravenous clindamycin and oral tetracycline has been used for many years as a treatment for active rheumatoid arthritis (RA), despite the absence of good evidence for its efficacy. A single-blind pilot study of this therapy suggested that a double-blind placebo-controlled trial was warranted. Methods. Patients with active RA were randomised in a 2u2009:u20091 ratio to receive active treatment or placebo for 25 weeks. The active treatment consisted of intravenous clindamycin in a reducing regime, and oral tetracycline twice daily three times a week. 50 patients were to be recruited. The primary outcome measure was the proportion of patients achieving an ACR20 response. Results. An interim statistical analysis was performed after 20 patients had completed the study. Two patients in the active group achieved an ACR20 response, with none in the placebo group (NS). There was a better ESR20 response in the placebo group (P = .02). There were no other significant differences between the groups. The results indicated that it was unlikely that a significant difference in ACR20 response would emerge if the remaining 30 patients were recruited. The trial was therefore halted. Conclusion. This antibiotic regime is unlikely to be a valuable therapy for active rheumatoid arthritis.

Liver Resection for Colorectal Metastases: Results and Prognostic Factors

For patients who have colorectal metastasis to the liver, surgical resection is the only treatment option that offers long term survival. Five year survival rates following surgical resection have been documented to be between 25% and 40%.1-6 The patients in these trials are highly selected, but no other form of therapy has shown comparable results. During the last 15 years it has become increasingly clear that liver resections, both minor and major, may be performed safely. Perioperative morbidity rates range between 10% and 50% and mortality rates between 0% and 5%.1-6