Biomedical subjects
Publications and source records attributed to C Varma.
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BACKGROUND: Device closure of an atrial septal defect (ASD) results in symptom-reduction, right heart remodelling and lower pulmonary artery pressures. However it is unclear if there is a chronological limit to these benefits and whether device closure is safe in elderly subjects. The aim of this study was, therefore, to assess the safety and efficacy of device closure in patients >60 years. METHODS: Retrospective study of Amplatzer Septal Occluder device closures from a single institution (May 1999-August 2002). RESULTS: Fifty subjects aged >60 years (range 60-85 years) had ASD device closure (27% of the total cohort). Defect size and shunt size were similar for both younger and older groups (2.2:1 in both groups, p=0.9) as were procedural duration, fluoroscopy time and device size deployed. Baseline right ventricular (RV) systolic pressure ((younger vs. older) 39 vs. 49 mmHg, p<0.001) and right ventricular size (45 vs. 51 mm, p<0.001) were greater in the older group. Following closure RV systolic pressure (49 vs. 45 mmHg, p<0.01) and RV size (51 vs. 44 mm, p=0.01) decreased in the older group. CONCLUSION: Device closure of an ASD can be performed safely in older patients. The right heart shows signs of remodelling even in elderly subjects.
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Atherosclerosis is a dynamic process and timely introduction of pharmacological treatment can have a significant bearing on the patient's health and outcome. In addition to treating the culprit lesion mechanically, admission for percutaneous coronary interventions (PCI) for coronary artery disease (CAD) gives an opportunity for the interventional cardiologist to optimize medical therapy. The aim of this review is to provide an overview of the current medical literature pertaining to cardiovascular (CV) risk reduction and vascular event prevention in the setting of PCI, with emphasis on antiplatelet therapies, beta-blockers, HMG-Co A reductase inhibitors (statins) and angiotensin-converting enzyme inhibitors, with regard to therapy optimization during PCI and for chronic CAD. We discuss the effects of these oral therapies in reducing ischaemic events, thus augmenting the benefits of PCI, as well as preventing recurrent CV events after the procedure.
BACKGROUND AND OBJECTIVE: Hereditary medullary thyroid carcinoma (MTC) is caused by germline mutations of the RET proto-oncogene. A genotype - phenotype correlation has been established, showing clustering of mutations in exons 10 and 11 in classical MEN 2 A syndrome, in exon 16 codon 918 in MEN 2 B syndrome and in exons 13-15 in familial MTC. A line of evidence suggested that the development and the aggressiveness of MTC in the different cancer syndromes is variable. Aim of this study was to compare the phenotype of exon 13-15 mutations with that of exon 11 mutation and possibly draw therapeutical consequences. PATIENTS AND METHODS: We compared the phenotype of 47 patients with mutations in exon 13-15 with 66 patients with exon 11, codon 634 mutation, the classical MEN2A. Patients were further subdivided as index and screening patients. RESULTS: Mean age of 19 index patients with codon 790, 791, 804 or 891 mutation was significant higher compared with 18 index patients with codon 634 mutation (mean age at diagnosis 50+/-12 years; range 30-69 y vs mean age 31+/-9 years; range 17-49 y), tumor stage at operation was favourable (C-cell hyperplasia n = 1; stage I n = 8; II n = 3; III n = 2; IV n = 2; no operation n = 1; no information n = 2 vs stage I n = 3; stage II n = 6; stage III n = 4, no information n =5), cure rate was better (56 % vs 38 %) and the death rate was lower (n = 2 vs n = 4). In screening patients no differences concerning the age, tumor stage, cure and death rate between patients with exons 13-15 and codon 634 mutations were seen. CONCLUSIONS: MTC in patients with exon 790, 791, 804, 891 mutations displayed a late onset and an indolent course compared to codon 634 mutation, this has to be taken into account when recommending timing and extent of prophylactic surgery.
A case of stenting for native coarctation is described in a 65-year-old female with a fatal dissection after implantation. The histology of the aorta in coarctation and in the elderly is described. The experience of stenting in older patients is reviewed and discussed.
Biventricular pacing has been suggested as offering greater hemodynamic benefit than single site pacing in patients with advanced heart failure and left bundle branch block. This was tested using acute multisite pacing. Eighteen such patients were atrialsensed, ventricular multisite paced in random order for 5 minutes. The best achieved measure of cardiac output (CO), pulmonary capillary wedge pressure (PCWP) and left ventricular (LV) + dP/dtmax at RV, LV, and biventricular pacing sites compared. Baseline PCWP, CO, and LV + dP/dtmax were 20 +/- 10 mmHg 4.8 +/- 1.3 L/min and 680 +/- 173 mmHg/s respectively. In all 18 patients CO and in 17 of 18 patients LV + dP/dtmax and PCWP improved with pacing. In the group as a whole, no significant hemodynamic difference between pacing sites was observed in PCWP (pacing site RV 19 +/- 10 mmHg, LV 17 +/- 10, biventricular 18 +/- 11) or CO (RV 5.2 +/- 1.5 L/min, LV 5.1 +/- 1.5, biventricular 5.3 +/- 1.7). Increased stroke volume/PCWP with LV (5.6 +/- 3.7 mLs/mmHg) and biventricular pacing (5.4 +/- 4.0) were not significantly greater compared to RV pacing (4.7 +/- 3.0, ANOVA P = 0.20). Increase in LV + dP/dtmax with pacing at LV (814 +/- 190 mmHg/s) and biventricular (839 +/- 290) sites was not significantly greater than the increase with RV pacing (769 +/- 203 mmHg/s, ANOVA P = 0.30). Pacing in patients with heart failure and conduction delay can produce a hemodynamic benefit. There is individual variation in the pacing site that leads to the greatest improvement. In the group as a whole, biventricular and LV pacing produced only modest improvements compared to RV pacing.
OBJECTIVE: To determine the effect of multisite pacing on left ventricular function. DESIGN: Prospective observational study. PATIENTS: 18 patients with heart failure with a dilated poorly functioning left ventricle (LV) and left bundle branch block. INTERVENTIONS: Pacing for 5 minutes in random order at the right ventricle (RV) apex, RV outflow tract, mid posterolateral LV, RV apex and LV simultaneously, and RV outflow tract and LV simultaneously. The best achieved measurements with RV, LV, and biventricular pacing were compared. MAIN OUTCOME MEASURES: LV dimension, filling characteristics, and long axis indices were measured on echocardiography simultaneously with LV pressure. Cycle efficiency (%)--that is, the ratio of the area of the acquired pressure dimension loop to that of the ideal loop for that segment--quantified coordination. RESULTS: The pacing site that gave the best achieved cycle efficiency differed between patients (biventricular in five, LV in two, RV in seven, and no site in four). In patients with baseline incoordination (cycle efficiency < or = 72%, n = 12) cycle efficiency improved significantly with RV pacing (cycle efficiency 76%, p = 0.01) but not with LV (65%) or biventricular (67%) pacing. LV based pacing induced premature short axis contraction in a subset of patients (n = 4), which was associated with a prolonged time from the Q wave on the ECG to the onset of inward movement of the long axis (from apex to mitral ring): biventricular 145 ms, LV 105 ms, RV 85 ms (biventricular v RV, p < 0.05). Excluding patients with baseline incoordination in whom premature activation occurred, pacing at all sites led to a similar increase in cycle efficiency (RV 78%, LV 72%, biventricular 73%). CONCLUSIONS: Ventricular coordination can be improved with pacing in patients with baseline incoordination. Short and long axis fibres may be asynchronised in a subset of patients with LV or biventricular pacing, which may worsen coordination. The clinical significance of these findings remains to be defined.
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Pacing for patients with severe heart failure without bradyarrhythmia has been proposed as an addition to medical therapy over the past decade. Alteration of the normal electrical activation sequence of the heart modifies its mechanical action, especially when ventricular function is poor. Both the site of ventricular-lead placement and timing with the atria have been manipulated in attempts to alleviate the symptoms of heart failure. Most recently, in addition to the conventional two leads used for pacing, a third lead to pace the left ventricle has been advocated in some patients with heart failure. We review the evidence for pacing in heart failure.
BACKGROUND: One third of patients with chronic heart failure have electrocardiographic evidence of a major intraventricular conduction delay, which may worsen left ventricular systolic dysfunction through asynchronous ventricular contraction. Uncontrolled studies suggest that multisite biventricular pacing improves hemodynamics and well-being by reducing ventricular asynchrony. We assessed the clinical efficacy and safety of this new therapy. METHODS: Sixty-seven patients with severe heart failure (New York Heart Association class III) due to chronic left ventricular systolic dysfunction, with normal sinus rhythm and a duration of the QRS interval of more than 150 msec, received transvenous atriobiventricular pacemakers (with leads in one atrium and each ventricle). This single-blind, randomized, controlled crossover study compared the responses of the patients during two periods: a three-month period of inactive pacing (ventricular inhibited pacing at a basic rate of 40 bpm) and a three-month period of active (atriobiventricular) pacing. The primary end point was the distance walked in six minutes; the secondary end points were the quality of life as measured by questionnaire, peak oxygen consumption, hospitalizations related to heart failure, the patients' treatment preference (active vs. inactive pacing), and the mortality rate. RESULTS: Nine patients were withdrawn from the study before randomization, and 10 failed to complete both study periods. Thus, 48 patients completed both phases of the study. The mean distance walked in six minutes was 22 percent greater with active pacing (399+/-100 m vs. 326+/-134 m, P<0.001), the quality-of-life score improved by 32 percent (P<0.001), peak oxygen uptake increased by 8 percent (P<0.03), hospitalizations were decreased by two thirds (P<0.05), and active pacing was preferred by 85 percent of the patients (P<0.001). CONCLUSIONS: Although it is technically complex, atriobiventricular pacing significantly improves exercise tolerance and quality of life in patients with chronic heart failure and intraventricular conduction delay.
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QT interval has been determined in 103 monozygotic (MZ) and 198 dizygotic (DZ) female twins. Mean values of corrected QT (QTc) were almost identical for both groups at 413 ms (MZ) and 412 ms (DZ). There was a significant age and environmental effect on QT interval. Heritability explained about 25% of the variation in QT. Further research will show whether any of the genes known to cause Long QT syndrome have any effect on QT interval at the sub-clinical level. Journal of Human Hypertension (2000) 14, 389-390
PURPOSE: Laparoscopic donor nephrectomy is an established procedure in the porcine model. We sought to compare intraoperative variables between live laparoscopic (LAP) and laparoscopy-assisted (LAP-A) donor nephrectomy. MATERIALS AND METHODS: Eight domestic pigs underwent either traditional laparoscopic donor nephrectomy (N = 4) or laparoscopy-assisted donor nephrectomy (N = 4) using the Pneumosleeve followed by conventional heterotopic autotransplantation. RESULTS: No significant differences were noted between the groups with regard to vessel length, ureteral length, or postoperative urine output. The operating room time was 108+/-12 minutes in the LAP group v 75.8+/-10.3 minutes in the LAP-A group (P = 0.0065). Although the difference was not statistically significant, warm ischemic time, tended to be lower in the LAP-A than the LAP group: 70+/-3.0 seconds v 135+/-57 seconds, respectively (P = 0.059). Graft survival was identical in the two groups. CONCLUSION: Laparoscopy-assisted (via Pneumosleeve) live donor nephrectomy shortens the operative time without affecting graft survival in the domestic swine model.
The aim of this study was to audit the management of hyperlipidaemia in a cohort of 206 consecutive patients, with known or suspected coronary artery disease, referred for diagnostic coronary angiography. The association of lipid subfraction values with the presence and extent of coronary artery disease was explored to identify the indices of greatest potential value to the hospital cardiologist, in the management of secondary prevention. Patients were questioned about previous lipid tests performed, advice received and treatment prescribed. Referral letters and hospital notes were reviewed to identify documentation of lipid results and treatment strategies. De novo fasting lipid estimations were obtained on 205 subjects at the time of catheterization. In only 46/206 (22%) cases was some form of lipid result recorded in the existing hospital notes or referral documentation. No patient was aware of the levels of the high or low density lipoprotein cholesterol subfractions (HDL, LDL) nor were these specifically recorded, or the subject of clinical comment, in any of the referral documentation. Patients who knew their total cholesterol (in mmol.1-1) result either as a value or as a "high' or "normal' categorization proved accurate witnesses. In keeping with other angiographic studies, we found that low values of HDL and high TC/HDL ratios were significantly associated with both disease presence and extent. Total cholesterol, calculated LDL and triglyceride levels had no such association. In the group as a whole and despite current therapy, 169/206 (82%) patients had a total cholesterol > 5.2 and 163/206 (79%) a TC/HDL ratio > 5. Only 22 (11%) patients were on drug therapy with a further 43 (21%) practising dietary modification. In the vast majority of subjects receiving some form of lipid intervention, target lipid levels had not been achieved. This study identifies the need for more intensive management of hyperlipidaemia in patients with coronary artery disease. Knowledge of HDL levels may be of value in guiding lipid secondary prevention management in the patient population evaluated at an angiographic centre.
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One of the major functions of cytokines is their ability to regulate cell growth and differentiation. The complexity of this process has been highlighted by recent studies on murine thymocytes; it has been shown that a number of cytokines interact to regulate thymocyte growth. We have investigated the effects of interleukin 4 (IL-4) and interleukin 7 (IL-7) on human thymocyte proliferation. Although maximal proliferation was dependent upon the presence of the mitogen phytohaemagglutinin (PHA), IL-7 alone stimulated thymocyte growth. In order to determine if this proliferation was due to the induction of IL-2, this pathway was inhibited by the addition of blocking antibody to the IL-2 receptor. Proliferation induced with IL-7 plus PHA, but not that induced by IL-7 alone, could be blocked by this treatment. In contrast, IL-4 stimulated thymocyte proliferation only in the presence of PHA; this proliferation was not inhibited by antibodies to the IL-2 receptor. Our findings show that both IL-7 and IL-4 can act as growth factors for human thymocytes, and that these cytokines stimulate proliferation through distinct mechanisms.
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