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Biomedical subjects

D Skudicky

Publications and source records attributed to D Skudicky.

At least 19 recordsLinked to original sources
PubMed2000

Peripartum cardiomyopathy: analysis of clinical outcome, left ventricular function, plasma levels of cytokines and Fas/APO-1.

OBJECTIVES: 1) To evaluate the outcome of patients with peripartum cardiomyopathy (PPC) on current treatment for heart failure, 2) to assess the circulating plasma levels of cytokines and Fas receptors and 3) to identify predictors of prognosis. BACKGROUND: Previous studies in patients with PPC were done when angiotensin-converting enzyme (ACE) inhibitors and beta-adrenergic blocking agents were not routinely used in heart failure. Inflammatory cytokines play an important role in the pathogenesis and progression of heart failure of other etiologies. However, there is a paucity of data regarding cytokine expression in patients with PPC. Plasma concentrations of Fas receptors (an apoptosis-signalling receptor) have not been reported in this population. METHODS: We followed prospectively 29 consecutive black women with PPC. All patients were treated with diuretics, digoxin, enalapril and carvedilol. Echocardiograms were performed at baseline and after six months of treatment. Cytokine and soluble Fas/APO-1 plasma levels were measured at baseline. RESULTS: Tumor necrosis factor-alpha, interleukin-6 and Fas/APO-1 levels were significantly elevated in the study patients compared with 20 healthy volunteers. Eight patients died. sFas/APO-1 levels were significantly higher in patients who died compared with survivors (8.98 +/- 4.5 vs. 5.33 +/- 3 U/ml, respectively, p = 0.02). At six months, ejection fraction improved from 26.7 +/- 10 to 42.7 +/- 16%, p = 0.00003, with an increment of more than 10 U in 10 patients (28.1 +/- 4 to 51.9 +/- 8%, p = 0.000008). CONCLUSIONS: Cytokine and sFas levels are elevated in patients with PPC. Despite treatment with ACE inhibitors and beta-blockers, mortality remains high. However, in 34% of the patients, left ventricular function almost completely normalized.

Adult↗
PubMed1999

Association of left ventricular systolic performance and cavity size with angiotensin-converting enzyme genotype in idiopathic dilated cardiomyopathy.

The insertion-deletion (ID) polymorphism of the angiotensin-converting enzyme (ACE) gene is a marker linked to differences in plasma and cardiac ACE activity as well as to an increased mortality in patients with idiopathic heart failure. We examined the possibility that ACE gene ID variants are associated with differences in left ventricular (LV) systolic performance or internal LV dimensions in a high-risk cohort of patients with idiopathic dilated cardiomyopathy (IDC). The ACE genotype was determined in 171 patients selected with IDC in New York Heart Association functional class II to III heart failure and with a LV ejection fraction of < or = 40%. Left ventricular performance and dimensions were assessed using echocardiography (n = 161) and radionuclide ventriculography (n = 169). The frequency of ACE gene ID alleles was not different in the study versus non-age-matched (n = 171; odds ratio 0.94) and age-matched (n = 106, odds ratio 0.88) control groups. Ejection fraction was found to be worse in patients with the DD genotype (echocardiography, DD = 23.5 +/- 0.70, ID + II = 26.8 +/- 0.8, p = 0.009; ventriculography, DD = 21.7 +/- 0.9, ID + II = 25.3 +/- 0.8, p = 0.003). LV end-systolic and end-diastolic diameters were increased in patients with the DD genotype. Multifactor regression analysis showed the ACE genotype to be an independent predictor of both ejection fraction (echocardiography, p <0.02; ventriculography, p <0.03) and end-diastolic diameter (p <0.02). In conclusion, the results of this study indicate that the DD genotype of the ACE gene is independently associated with both a reduced LV systolic performance and an increased LV cavity size in patients with IDC.

Aged↗
PubMed1999

Antihypertensive monotherapy with nisoldipine CC is superior to enalapril in black patients with severe hypertension.

A single-center, prospective double-blind randomized trial was conducted to compare the efficacy and safety of the calcium channel blocker nisoldipine in a sustained release coat-core formulation (CC), titrated from 10 mg to 40 mg daily, with the angiotensin converting enzyme inhibitor enalapril, titrated from 10 to 40 mg daily, in the treatment of black South African patients with severe hypertension (sitting diastolic blood pressure [DBP] between 115 and 140 mm Hg, confirmed by 24-h ambulatory blood pressure monitoring). Treatment target was a sitting DBP < 95 mm Hg by the 9th week of treatment. This was followed by a 4-month open phase using nisoldipine CC 10 to 60 mg daily. Ninety-six patients had complete data at baseline, and at the end of the double-blind and open phases, and were included in this analysis. In both groups, all patients required titration up to the maximal dose of double-blind medication. Monotherapy with nisoldipine CC, but not enalapril, significantly reduced both sitting and 24-h ambulatory blood pressure (BP). Twenty-four-hour BP in the nisoldipine CC group decreased from 179+/-14 / 118+/-7 to 144+/-16 / 94+/-10 mm Hg (P < .0001) versus 181+/-13 / 117+/-5 to 171+/-17 / 110+/-11 mm Hg in the enalapril group (P = ns). The profound decrease in blood pressure achieved with nisoldipine CC was accompanied by a significant reduction in left ventricular [LV] mass index, observed after only 2 months of treatment (from 146+/-40 to 129+/-35 g/m2, P = .05). In contrast, enalapril had no effect on LV mass (from 139+/-36 to 142+/-50 g/m2, P = NS). The antihypertensive effect of nisoldipine CC was further demonstrated in the open phase, during which 24-h BP decreased from 180+/-14 / 118+/-6 mm Hg (at baseline) to 142+/-16 / 92+/-10 mm Hg at the end of the 16-week open phase (P < .0001). This effect was sustained with trough-to-peak ratio of 74% for systolic and 67% for diastolic BP, with further regression in LV mass. Reduction in 24-h systolic BP to < 135 mm Hg was associated with a greater degree of regression of LV mass index in patients treated with nisoldipine CC. The incidence of adverse events in both groups was low and both nisoldipine CC and enalapril were well tolerated. The incidence of significant ventricular arrhythmia was also low and did not change with treatment. In conclusion, our findings suggest that nisoldipine CC administered once daily could be considered as a suitable first-line antihypertensive agent in black patients with severe hypertension, based on its profound and sustained blood-pressure-lowering effect, associated with significant regression of left ventricular mass and its low side effect profile.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Long-term follow-up of rheumatic patients undergoing left-sided valve replacement with tricuspid annuloplasty--validity of preoperative echocardiographic criteria in the decision to perform tricuspid annuloplasty.

Between September 1989 and December 1991, modified De Vega tricuspid annuloplasty was performed in 43 patients who survived surgery for mitral or mitral plus aortic valve replacement. The preoperative indications for tricuspid annuloplasty were moderate to severe tricuspid regurgitation (TR) in 33 patients and mild or no TR but with a dilated tricuspid annulus (> or =30 mm) as measured by 2-dimensional echocardiography at end-diastole in 10 patients. The mean age was 31 +/- 13 years. The mean duration of follow-up was 57 +/- 18 months. Overall long-term mortality was 12%. On Doppler color flow mapping, postoperative severe TR was present in 1 patient and moderate TR in 4 patients at latest follow-up. The tricuspid annulus diameter decreased from 37 +/- 5 mm preoperatively to 24 +/- 6 mm at latest follow-up. During the study period, an additional 77 patients underwent mitral valve replacement or double valve replacement, but without tricuspid annuloplasty. Within this group, 38 patients had a preoperative tricuspid annulus diameter of > or =30 mm, and 5 of these patients (13%) developed moderate or severe TR in the postoperative period, which may have been prevented had clinicians adhered to the preoperative indications for tricuspid annuloplasty. Thus, preoperative echocardiographically documented moderate or severe TR or a tricuspid annulus diameter of > or =30 mm are valid indications for performing tricuspid annuloplasty; modified De Vega tricuspid annuloplasty is a durable procedure in rheumatic patients; it appears that reducing the diastolic tricuspid annulus diameter to 24 mm is adequate to prevent residual TR in the long term.

Adult↗
PubMed1998

Randomised investigation of effects of pentoxifylline on left-ventricular performance in idiopathic dilated cardiomyopathy.

BACKGROUND: There is accumulating evidence that inflammatory cytokines have an important role in the pathogenesis of heart failure. Plasma concentrations of tumour necrosis factor alpha (TNF-alpha) are high in heart failure and have been correlated with the severity of symptoms. Pentoxifylline suppresses the production of TNF-alpha. This study aimed to assess the effects of pentoxifylline on left-ventricular function and functional class in patients with idiopathic dilated cardiomyopathy. METHODS: We undertook a single-centre, prospective, double-blind, randomised, placebo-controlled trial, in which 28 patients with idiopathic dilated cardiomyopathy were assigned pentoxifylline 400 mg three times daily or matching placebo. Clinical, echocardiographic, and radionuclide assessments were done at baseline and after 6 months of treatment. Primary endpoints were New York Heart Association (NYHA) functional class and left-ventricular function. FINDINGS: Baseline characteristics were similar in the two groups. Four patients died during the study period, all in the placebo group. After 6 months of treatment, the proportion of patients in NYHA functional class I or II was higher in the pentoxifylline group than in the placebo group (14/14 vs 10/14; p=0.01), and ejection fraction was higher in the pentoxifylline group than in the placebo group (mean 38.7% [SD 15.0] vs 26.8% [11.0], p=0.04). At 6 months, TNF-alpha plasma concentrations were significantly lower in the pentoxifylline-treated group than in the placebo group (2.1 [1.0] vs 6.5 [5.0] pg/mL, p=0.001). INTERPRETATION: Our results suggest that pentoxifylline improves symptoms and left-ventricular systolic function in patients with idiopathic dilated cardiomyopathy. These results must be confirmed in larger-scale trials.

Cardiomyopathy, Dilated↗
PubMed1998

Long-term follow-up of St. Jude Medical prosthesis in a young rheumatic population using low-level warfarin anticoagulation: an analysis of the temporal distribution of causes of death.

This study assesses the long-term (mean 52+/-24 months) performance of the St. Jude Medical (SJM) valve in 200 young (mean age 31+/-13 years) rheumatic patients on low-level warfarin anticoagulation combined with dipyridamole. Follow-up was 95% complete and comprised 867 patient-years. There were 33 deaths (3.8%/patient-year). Death was valve related in 12 cases and due to left ventricular dysfunction in 10. Death due to left ventricular dysfunction occurred earlier after surgery than death due to other causes (10+/-7 vs 29+/-18 months, p <0.005); these patients had larger preoperative left ventricular dimensions than the rest of the group (end-systolic diameter 51+/-13 vs 37+/-16 mm, end-diastolic diameter 66+/-13 vs 50+/-19 mm, p = 0.006). Actuarial probability of survival was 81% at 86 months and probability of event-free survival was 71%. The median international normalized ratio was 1.88+/-0.54. Thromboembolism (13 events) occurred at a linearized rate of 1.5%/patient-year. There were 11 major bleeding episodes (1.3%/patient-year), 4 cases of prosthetic valve endocarditis (0.8%/patient-year), and 12 paraprosthetic leaks (1.4%/patient-year). No valve obstructions or reoperations occurred. Thus, the SJM valve performs well on low-level anticoagulation combined with dipyridamole. Left ventricular dysfunction was a common cause of death in the early postoperative period.

Actuarial Analysis↗
PubMed1997

Time-related changes in left ventricular function after double valve replacement for combined aortic and mitral regurgitation in a young rheumatic population. Predictors of postoperative left ventricular performance and role of chordal preservation.

BACKGROUND: The long-term effects of double valve replacement on left ventricular function in patients with combined severe rheumatic aortic and mitral regurgitation have not been reported previously. Furthermore, the importance of chordal preservation in this group of patients is unknown. METHODS AND RESULTS: Serial clinical and echocardiographic evaluations were performed prospectively in 44 patients who underwent double valve replacement for combined aortic and mitral regurgitation. Chordae to the posterior mitral leaflet were preserved in 27 patients. Mean follow-up was 40 +/- 19 months. Left ventricular end-diastolic diameter decreased significantly 3 months after surgery (from 66 +/- 10 to 52 +/- 11 mm; P < .001) without a substantial change in end-systolic diameter, resulting in a significant decline in ejection fraction (from 60 +/- 9% to 48 +/- 15%; P < .001). At 1 year, a significant reduction in end-systolic dimension was observed without a concomitant decline in end-diastolic diameter, thus normalizing the ejection fraction (55 +/- 12%; P = .17 versus baseline). No further changes were seen at latest follow-up. Multivariate regression analysis identified baseline end-systolic diameter and ejection fraction as independent predictors of postoperative systolic performance. Chordal preservation did not emerge as a univariate or multivariate predictor. CONCLUSIONS: After an initial postoperative decline in ejection fraction, normalization in left ventricular systolic function may be expected 1 year after double valve replacement for combined rheumatic mitral and aortic regurgitation. End-systolic diameter and ejection fraction are the only independent predictors of postoperative left ventricular performance.

Adolescent↗
PubMed1994

Frequency of prosthetic valve-related complications with very low level warfarin anticoagulation combined with dipyridamole after valve replacement using St. Jude Medical prostheses.

The safety of a very low level of anticoagulation combined with dipyridamole in a rheumatic population (mean age 31 +/- 13 years) with the St. Jude Medical (SJM) prosthesis has not yet been tested. Furthermore, no data are available on the safety of relatively infrequent monitoring of anticoagulation levels and of the necessity for different therapeutic targets according to valve position, number of risk factors, and other baseline risk factors for thromboembolism. In this study, the performance of the SJM prosthesis was tested using a target international normalized ratio (INR) of 2.0 to 2.5 combined with dipyridamole 300 mg/day applied uniformly to all patients. Clinical, biochemical, and echocardiographic data were acquired prospectively in 200 consecutive patients at 3-month intervals. Follow-up (mean 27 +/- 13 months) was complete in 95% of patients. Thirteen patients died (2.9%/patient year). Severe left ventricular dysfunction was the cause of death in 10 of 13 patients. Probability of survival (Kaplan-Meier) was 0.92 at 36 months and of event-free survival 0.84 at 36 months. The median INR was 2.0 +/- 0.9. Valve obstruction did not occur, and there were 3 thromboembolic events (0.6%/patient year). Incidence of bleeding was 1.6%/patient year (n = 7) and was major (hemorrhagic stroke) in 1 (0.2%/patient year). Thus, the SJM prosthesis performs very well despite the use of very low level warfarin anticoagulation combined with dipyridamole. A 3-month assessment of the anticoagulation level is safe. Left ventricular dysfunction rather than valve-related complications is the leading cause of mortality in this population.

Adult↗
PubMed1994

Effect of isradipine in black patients with very severe hypertension. 24-hour ambulatory blood pressure monitoring and echocardiographic evaluation.

Fifty consecutive black patients with very severe hypertension (sitting diastolic blood pressure > or = 120 mm Hg and systolic > or = 210 mm Hg by the conventional cuff method) were treated in an open-label study (without a placebo or active drug control group) for 3 months with a long-acting preparation of isradipine (Dynacirc SRO), during which time serial changes in 24-h ambulatory blood pressure monitoring (ABPM), left ventricular (LV) mass index, and LV systolic function were evaluated. Mean 24-h ABPM was reduced from 184 +/- 13/119 +/- 6 to 148 +/- 18/96 +/- 11 mm Hg at 3 months (P < .0001). The reduction in BP was sustained for 24 h after dosing. Simultaneous BP measurements using a conventional cuff method and Dinamap were significantly different from the ABPM pre- and posttherapy, suggesting a marked "white coat" pressor effect. LV mass index regressed from 143 +/- 36 to 122 +/- 32 g/m2 at 3 months (P < .02). Heart rate and mean body weight were unchanged. Left ventricular performance was not adversely affected. Cardiac index and fractional shortening changed insignificantly, from 2.6 +/- 0.6 to 2.7 +/- 0.5 L/min/m2, and from 28 +/- 6 to 31 +/- 7%, respectively. Adverse effects were few and tended to disappear during the treatment period. All of the clinical laboratory parameters tested remained unchanged. We conclude that in this group of patients long-acting isradipine 1) showed a marked and sustained antihypertensive action demonstrated by 24-h ABPM; and 2) was well tolerated and associated with LV mass regression without adverse effect on systolic cardiac function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Prediction of outcome after valve replacement for rheumatic mitral regurgitation in the era of chordal preservation.

BACKGROUND: Noninvasive predictors of important outcomes after valve replacement for mitral regurgitation have not been examined in a rheumatic population (in whom the results of valve repair are suboptimal) in the era of chordal preservation. Timing of valve replacement thus remains a difficult question in rheumatic mitral regurgitation. METHODS AND RESULTS: Of 278 patients followed after valve replacement, 66 had pure or predominant mitral regurgitation, and in 61 of these the etiology was rheumatic. The mean age was 24 years. After a mean follow-up of 24 +/- 10 months, the ability of preoperative clinical and echocardiographic data to predict outcome was assessed prospectively, and the possible impact of chordal preservation (n = 35) on survival and post-operative left ventricular function was examined retrospectively. There were no perioperative deaths. There were six postoperative deaths, all the result of heart failure and all related to left ventricular dysfunction. The mean probability of survival was .90 at 16 months. In a stepwise Cox proportional hazards regression analysis, the only independent predictor of postoperative death was preoperative end-systolic diameter. According to a logistic model, the probabilities of death (n = 6) and death or severe heart failure (n = 7) increased abruptly at a preoperative end-systolic diameter of 51 mm (probabilities, .23 and .31, respectively), and the accuracy of this cut point for predicting outcomes was 97% and 98%, respectively. Multiple linear regression analysis identified a large preoperative end-systolic diameter and the need to use tricuspid annuloplasty as significant independent predictors of postoperative fractional shortening; the use of chordal preservation (n = 35) was not a predictor of postoperative fractional shortening. A good outcome was predicted at a preoperative end-systolic diameter of 40 mm: probability of death or heart failure was .0001, and predicted mean postoperative fractional shortening was 0.27 after mitral valve replacement without tricuspid annuloplasty. CONCLUSIONS: When preoperative end-systolic diameter is more than 50 mm, a poor postoperative outcome is predicted despite chordal preservation in relatively young patients with rheumatic mitral regurgitation, and alternative strategies should therefore be considered. When preoperative end-systolic diameter is 40 mm or less, an excellent outcome is predicted, and close observation without surgery would appear to be reasonable in the absence of symptoms.

Adult↗
PubMed1993

Effectiveness of amiodarone and electrical cardioversion for chronic rheumatic atrial fibrillation after mitral valve surgery.

Thirty consecutive patients with chronic rheumatic atrial fibrillation (AF) > or = 3 months after successful mitral valve surgery and left atrial diameter < or = 60 mm were treated with oral amiodarone. Protocol included high loading dosages of amiodarone for 4 weeks, and if conversion to sinus rhythm (SR) was not achieved then electrical cardioversion was performed. Patients converted to SR were maintained on low-dose amiodarone for another 4 weeks when treatment was discontinued. Overall, 23 patients (77%) converted to SR after 4 weeks of therapy: 12 (40%) taking amiodarone alone and 11 (37%) with the addition of electrical cardioversion. The duration of AF > 48 months was an adverse factor in the ability to restore SR. Sixteen patients (70%) remained in SR at a mean follow-up of 17 months. The duration of AF < or = 48 months alone or in combination with left atrial diameter < or = 45 mm were the best predictors for long-term maintenance of SR. Thus, short-term amiodarone with or without electrical cardioversion is effective and safe in the treatment of chronic rheumatic AF after mitral valve surgery. The duration of AF and left atrial size can be used to identify patients with successful outcome.

Adult↗
PubMed1993

Results of percutaneous balloon mitral valvotomy in young adults.

The results of percutaneous balloon mitral valvotomy (PBMV) were evaluated in 235 young patients (mean age 29 +/- 11 years) with symptomatic rheumatic mitral stenosis, and the single-balloon Inoue technique was compared with the double-balloon Mansfield technique. PBMV was associated with a significant increase in Gorlin mitral valve area (0.78 +/- 0.23 to 1.61 +/- 0.64 cm2; p < 0.001), and improvement in New York Heart Association functional class (2.78 +/- 0.59 to 1.28 +/- 0.58; p < 0.001). Mitral regurgitation increased significantly (0.4 +/- 0.6 to 1.3 +/- 1.0; p < 0.001), but was significant (> or = 3+) only in 19 patients (8%). Comparison of the Inoue and Mansfield techniques showed a significantly lower Gorlin mitral valve area after PBMV (1.55 +/- 0.56 vs 1.74 +/- 0.74 cm2; p < 0.05), but a lower incidence of mitral regurgitation by color Doppler echocardiography (1.1 +/- 0.7 vs 1.5 +/- 0.8; p < 0.05) in the Inoue group. Patients were divided into those with nonpliable (valve score > 8; group I) and pliable (score < or = 8; group II) valves. Although significant increases in mitral valve area were obtained in both groups, mitral valve area by planimetry was significantly lower in group I (1.49 +/- 0.46 vs 1.86 +/- 0.44 cm2; p < 0.05), whereas there was no difference in the amount of color Doppler mitral regurgitation (1.5 +/- 1.0 vs 1.2 +/- 0.7; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Frequency and severity of intravascular hemolysis after left-sided cardiac valve replacement with Medtronic Hall and St. Jude Medical prostheses, and influence of prosthetic type, position, size and number.

Intravascular hemolysis occurs often in patients with mechanical heart valve prostheses, but in most cases is of mild degree and subclinical. The severity of hemolysis is reported to be related to the type, position and size of prostheses used, as well as the presence of valve malfunction. Hemolysis was evaluated in 170 patients with St. Jude Medical (SJM) and 80 patients with Medtronic Hall (MH) prostheses, with normal mechanical function. The presence and severity of hemolysis was assessed on the basis of serum lactic dehydrogenase, serum haptoglobin, blood hemoglobin and reticulocyte levels as well as the presence of schistocytes. Overall, patients with SJM prostheses had greater frequency (51.2 vs 18.7%, p < 0.005) and severity (p < 0.005) of hemolysis than patients with MH prostheses, irrespective of position and size. No patient had decompensated anemia. The frequency of hemolysis was similar in both groups with double-valve replacement, whereas severity was greater with SJM than MH prostheses (p < 0.001). The number and position of the prostheses were correlated with severity of hemolysis: Double-valve replacement and mitral position were correlated with greater hemolysis than single-valve replacement (p < 0.01) and aortic position (p < 0.01). Valve size, cardiac rhythm and time from operation did not correlate either with frequency or severity of hemolysis. It is concluded that in normally functioning SJM and MH prostheses: (1) hemolysis is frequent but never severe; (2) SJM demonstrates greater frequency and severity when compared with MH valve; and (3) number, position, but not size, significantly affect the severity of hemolysis.

Adult↗
PubMed1993

Pulmonary hypertension is a contraindication to beta-blockade in patients with severe mitral stenosis.

Intravenous atenolol was given to 31 patients just before balloon mitral valvotomy to assess the hemodynamic efficacy and safety of beta-blockade in mitral stenosis complicated by pulmonary hypertension. Hemodynamic response in patients with pulmonary resistance > 600 dynes.sec.cm-5 (group 2, n = 17) was compared with those (group 1, n = 14) with a resistance below this value. In addition to a higher pulmonary arterial resistance (by design), patients in group 2 had a higher systemic resistance, lower cardiac index, and smaller mitral valve area compared with those in group 1. After atenolol infusion, transmitral gradient and left atrial pressure improved similarly. In spite of the decline in left atrial pressure, pulmonary vascular resistance increased in both groups, more in group 2 (847 +/- 398 dynes.sec.cm-5 to 135 +/- 648 dynes.sec.cm-5) than in group 1 (291 +/- 149 dynes.sec.cm-5 to 363 +/- 200; p < 0.001 for drug effect and p = 0.027 for group effect by two-way analysis of variance). Cardiac index declined similarly from 2.77 +/- 0.51 L/min/m2 to 2.37 +/- 0.37 L/min/m2 in group 1 and from 2.33 +/- 0.58 L/min/m2 to 1.92 +/- 0.54 L/min/m2 in group 2. Systemic pressure tended to decline only in group 2 (mean aortic pressure, 89 +/- 12 mm Hg to 89 +/- 12 mm Hg in group 1 and 90 +/- 9 mm Hg to 83 +/- 12 mm Hg in group 2; p = 0.06 for group effect).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗