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Sudhir S Kushwaha

Publications and source records attributed to Sudhir S Kushwaha.

9 recordsLinked to original sources
PubMed2006

Association of angiotensin-converting enzyme inhibitors and serum lipids with plaque regression in cardiac allograft vasculopathy.

We assessed clinical predictors of the process of cardiac allograft vasculopathy (CAV) in 39 consecutive patients (mean 49 years old) using three-dimensional intravascular ultrasound (3-D IVUS) examination of the left anterior descending coronary artery at 36 +/- 38 months and 47 +/- 40 months after cardiac allotransplantation (TX). Compared with 17 patients with plaque progression, 22 patients with plaque regression were more likely to be male (P < .01), to have a higher use of angiotensin-converting enzyme inhibitors (ACEI, P < .05), and to have a lower volumetric remodeling index (P < .001). The changes in plaque volume correlated with the changes in total cholesterol (P < .005) and low-density lipoprotein cholesterol (P < .02). Plaque progression of CAV was independently associated with time after TX, hypertension, nonuse of ACEI, donor age, and changes in total cholesterol and triglycerides. In conclusion, plaque progression is associated with positive vascular remodeling and plaque regression is associated with lower serum lipids and ACEI in patients after TX.

Adult↗
PubMed2005

Prevalence, pathophysiology, and clinical significance of post-heart transplant atrial fibrillation and atrial flutter.

BACKGROUND: Atrial rhythm disturbances, in particular atrial fibrillation (AF) and flutter (AFL), are common in the denervated transplanted heart. However, there is a relative paucity of data in the prevalence, mechanism of arrhythmia, and long-term significance. OBJECTIVES: (1) Determine the prevalence of AF and AFL in heart transplant patients, (2) define the echo/Doppler features associated with arrhythmia, and (3) evaluate the impact of arrhythmia on long-term survival. METHODS: All patients who received an orthotopic heart transplant at the Mayo Clinic, Rochester, Minnesota, between 1988 and 2000 were included. Analysis of serial electrocardiograms and Holter monitor records provided evidence of AF or AFL development. Variables including general patient demographics, histology-proven rejection numbers and grades, results of serial coronary angiography, endomyocardial biopsy specimens, and echocardiographic studies performed at 6 weeks and 3 years after transplant were obtained to determine variables predictive of arrhythmia development. RESULTS: There were 167 heart transplant recipients, of which 16 (9.5%) developed AF and another 25 (15.0%) developed AFL over 6.5 +/- 3.4 years. Patients who developed AF or AFL had lower left ventricular (LV) ejection fractions (56.6% +/- 1.6% vs 62.5% +/- 1.5%, p < 0.05), higher LV end-systolic dimensions (LVESD) (33.6 +/- 1.12 mm vs 29.7 +/- 0.97 mm, p < 0.01), higher right atrial volume indexes (43.2 +/- 12.3 ml vs 35 +/- 5.3 ml, p < 0.03), lower mitral deceleration time (145 +/- 8 msec vs 160 +/- 12 msec, p < 0.05), and lower late mitral annulus tissue a' velocities (0.06 +/- 0.005 cm/sec vs 0.08 +/- 0.01 cm/sec, p < 0.02) compared with an age- and gender-matched Sinus Rhythm Group. Grade 3 rejection was a time-dependent covariate predictor of AFL risk (hazard ratio [HR], 2.95; 95% confidence interval [CI], 1.3-6.6, p < 0.008) but not AF (HR, 2.264; 95% CI, 0.72-7.1; p = 0.10). Thirty-nine of 167 patients died: 13 in the arrhythmia group and 26 in the normal sinus rhythm group. Development of atrial dysrhythmia adversely affected the outcome in the first 5 years (p < 0.001) compared with normal sinus rhythm. Predictors of long-term mortality included AF/AFL (HR, 2.88; 95% CI, 1.38-5.96; p < 0.004), age at transplant (HR, 1.04; 95% CI, 1.00-1.07, p < 0.03), coronary artery disease (HR, 2.655; 95% CI, 1.25-5.64; p = 0.01), pre-transplant cardiac amyloidosis (HR, 5.02; 95% CI 2.37-10.62; p < 0.001), right atrial volume index (HR, 1.03; 95% CI, 1.00-10.7; p = 0.03), mitral deceleration time <160 msec (p < 0.01), and LVESD >30 mm (p < 0.04). CONCLUSION: Development of AF/AFL post-heart transplantation is not uncommon and is associated with decreased long-term survival. Cumulative effects of repeated moderate-to-severe (grade 3 or more) rejections that result in increased cardiac fibrosis are associated with the development of AFL, but not AF. Similarly advanced restrictive diastolic dysfunction caused by fibrosis from repeated moderate-to-severe (grade 3 or more) rejections was predominant in the patients with arrhythmia and was a marker of poor long-term outcome.

Adult↗
PubMed2005

Elevated donor troponin levels are associated with a lower frequency of allograft vasculopathy.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is considered a major cause of morbidity and mortality in transplant recipients and may reflect immune-mediated endothelial injury in response to the donor heart. Elevated troponin levels in the donor serum might provide a marker for this phenomenon; therefore, we evaluated the relationship of donor troponin levels to the development of CAV. METHODS: A retrospective analysis of troponin levels was undertaken from cardiac donor patients, and transplant recipients were monitored for the development of vasculopathy by angiography (N = 171). RESULTS: Angiographically significant CAV developed in 6% of transplantation patients and troponin levels were inversely related to the severity of CAV. CONCLUSIONS: Elevated donor troponin levels are not associated with the development of CAV but rather with a significantly reduced long-term risk of developing CAV, suggesting a possible protective effect of donor released protein.

Adult↗
PubMed2005

Sirolimus in cardiac transplantation: use as a primary immunosuppressant in calcineurin inhibitor-induced nephrotoxicity.

BACKGROUND: Calcineurin inhibitor (CNI) immunosuppressants are a major cause of renal dysfunction in cardiac transplant recipients, leading to increased morbidity and mortality. The aim of this study was to evaluate the efficacy and safety of CNI withdrawal and substitution with sirolimus as the primary immunosuppressant, and assess the effect on renal function in cardiac transplant recipients with CNI-induced renal impairment. METHODS: Thirty-four stable cardiac transplant recipients (range 1 to 14 years post-transplant) with CNI-induced nephrotoxicity (iothalamate clearance 25 to 50 ml/min) or cardiac allograft vasculopathy (CAV) were enrolled. Twelve patients (Group A) were prospectively enrolled for renal dysfunction. The remaining patients (n = 22, Group B) were converted to sirolimus on clinical grounds because of poor renal function or the presence of CAV. CNI was withdrawn gradually over 12 weeks. Sirolimus was started at 1 mg/day with titration over 2 weeks to achieve levels of 10 to 15 ng/ml. Echocardiograms and cardiac biopsies were performed to determine rejection. Adjunct immunosuppression was left unchanged. Follow-up iothalamate clearance was performed. A further 24 patients (Group C) were retrospective controls, stable (range 2 to 10 years post-transplant), and maintained on a standard CNI-based immunosuppressant regimen. RESULTS: Iothalamate clearance (C(i)) improved significantly (Group A baseline: 36.08 +/- 2.4 ml/min to 48.67 +/- 4.1 ml/min, p = 0.004; Group B baseline: 48.14 +/- 3.2 ml/min to 55.77 +/- 4.2 ml/min, p < 0.001) without exacerbating rejection or compromising cardiac function. By contrast, in controls, Group C, the baseline renal clearance declined from 40.04 +/- 1.86 ml/min to 34.63 +/- 1.6 ml/min over the course of 1 year (p < 0.01). CONCLUSIONS: Substitution of CNIs with sirolimus in cardiac transplant recipients is safe and effective and leads to an improvement in renal function, without compromise in cardiac function and rejection.

Aged↗
PubMed2003

Endothelial progenitor cells are decreased in blood of cardiac allograft patients with vasculopathy and endothelial cells of noncardiac origin are enriched in transplant atherosclerosis.

BACKGROUND: Recent studies in animals suggest that circulating recipient endothelial precursors may participate in the biology of transplant vasculopathy. It is currently unknown whether a similar interaction between recipient endothelial cells and the vessel wall occurs in human subjects undergoing allogeneic cardiac transplantation. METHODS AND RESULTS: Circulating endothelial cells and endothelial progenitor cells (EPCs) were quantified in 15 cardiac transplantation subjects with and without angiographic evidence of vasculopathy. In a separate series of experiments, the origin (donor or recipient) of transplant plaque endothelial cells was assessed in subjects who had undergone a gender-mismatched cardiac transplantation and had histological evidence of severe vasculopathy at the time of heart explantation. Circulating EPC outgrowth colonies in peripheral blood were significantly reduced in subjects with transplant vasculopathy compared with those without angiographic evidence of disease (EPC colony-forming units [CFUEPC]: 4.5+/-1.9 versus 15.1+/-3.7, P<0.05). There was no significant difference in circulating endothelial cell numbers as defined by day 4 culture acetylated LDL/lectin assay in either of these patient groups. In a separate group of 5 subjects who underwent gender-mismatched cardiac transplantation, there was a significant seeding of recipient endothelial cells (range: 1% to 24% of all luminal endothelial cells) in large-vessel lumen and adventitial microvessel lumen of arteriopathic vessels. No opposite-sex chimeric cells were observed in control gender-matched transplantation scenarios. CONCLUSIONS: These data suggest that the human cardiac transplant arteriopathy is associated with reduction in circulating endothelial precursors and with seeding of recipient-derived endothelial cells at the site of plaque development.

Adult↗
PubMed2003

Transplant immunosuppressant agents and their role in autoimmune rheumatic diseases.

This article examines immunosuppressant transplant agents used to treat the various rheumatic diseases. The older drugs of this type have been used in this dual role for decades. There is a new generation of immunosuppressant drugs with established use in the arena of transplantation medicine. Only recently have the potential rheumatologic applications for these agents been investigated. The authors review in depth the published experience with the newer agents. The authors also discuss novel rheumatologic uses for the older agents that have been described within the past year.

Autoimmune Diseases↗
PubMed2002

Catheter ablation of atrial flutter in a heart transplant recipient.

In the transplanted heart with biatrial anastomosis, atrial flutter is common and is amenable to catheter ablation. Although this arrhythmia is isthmus dependent, the unique atrial architecture with a suture line through the inferior vena cava-tricuspid annulus isthmus makes the substrate atypical. A cardiac transplant recipient with atrial flutter underwent successful catheter ablation. Five weeks after the procedure, the patient died of a myocardial infarction. The autopsy and histological findings are described and correlated with the electroanatomic map obtained during the ablation. Due to the atrial suture lines, atrial flutter following cardiac transplantation is an isthmus dependent arrhythmia with a different arrhythmogenic substrate. The electrical isthmus (atrial tissue from the tricuspid annulus to the suture line) in these hearts is smaller than the anatomic isthmus.

Atrial Flutter↗
PubMed2002

Partial normalization of the heart rate response to exercise after cardiac transplantation: frequency and relationship to exercise capacity.

OBJECTIVE: To determine the frequency of partial normalization of the heart rate response to graded exercise and its relationship to exercise capacity in cardiac transplant recipients. SUBJECTS AND METHODS: The study subjects were 95 adults (77 men, 18 women) who were available to perform a cardiopulmonary exercise test 1 year after orthotopic cardiac transplantation, which occurred between June 1988 and September 1998. All subjects received standard immunosuppressant medications. At the time of the exercise tests, the mean +/- SD age of the subjects was 49+/-14 years. The mean +/- SD resting left ventricular ejection fraction was 62%+/-8%. All subjects participated in a 6- to 8-week supervised exercise program, starting no later than 1 month after surgery. Subjects were given an exercise prescription for independent exercise training after finishing the supervised program. Self-reported weekly exercise training had a median value of 90 minutes (interquartile range, 0-210 minutes). Symptom-limited graded exercise was performed on a treadmill, with breath-by-breath analysis of expired air. RESULTS: For the entire cohort, peak exercise oxygen uptake was 19.9+/-4.8 mL x kg(-1) x min(-1) (61%+/-15% of age and sex predicted). Thirty-two subjects (34%) had a partially normalized heart rate response to graded exercise. The frequency was similar for men (25/77 [33%]) and for women (7/18 [39%]) and was independent of recipient or donor age. Peak exercise heart rate (147+/-18 vs 134+/-21 beats/min; P=.008) and heart rate reserve (46+/-15 vs 33+/-15 beats/min; P<.001) were greater for subjects with a partial normalization of heart rate response. Peak exercise oxygen uptake was similar for subjects with or without partial normalization of the heart rate response (20.9+/-5.8 vs 19.4+/-4.2 mL x kg(-1) x min(-1); P=.22). Submaximal exercise oxygen uptake during the first few minutes of exercise was also not affected by normalization of the heart rate response. CONCLUSION: At 1 year after cardiac transplantation, approximately one third of subjects had partial normalization of the heart rate response to graded exercise. However, a higher peak exercise heart rate and a larger heart rate reserve did not result in better aerobic exercise capacity.

Adult↗