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Biomedical subjects

W Ruzyllo

Publications and source records attributed to W Ruzyllo.

At least 19 recordsLinked to original sources

In vivo and in vitro examination of the functional significances of novel lamin gene mutations in heart failure patients.

CONTEXT: Lamin A/C (LMNA) gene variations have been reported in more than one third of genotyped families with dilated cardiomyopathy (DCM). However, the relationship between LMNA mutation and the development of DCM is poorly understood. METHODS AND RESULTS: We found that end stage DCM patients carrying LMNA mutations displayed either dramatic ultrastructural changes of the cardiomyocyte nucleus (D192G) or nonspecific changes (R541S). Overexpression of the D192G lamin C dramatically increased the size of intranuclear speckles and reduced their number. This phenotype was only partially reversed by coexpression of the D192G and wild type lamin C. Moreover, the D192G mutation precludes insertion of lamin C into the nuclear envelope when co-transfected with the D192G lamin A. By contrast, the R541S phenotype was entirely reversed by coexpression of the R541S and wild type lamin C. As lamin speckle size is known to be correlated with regulation of transcription, we assessed the SUMO1 distribution pattern in the presence of mutated lamin C and showed that D192G lamin C expression totally disrupts the SUMO1 pattern. CONCLUSION: Our in vivo and in vitro results question the relationship of causality between LMNA mutations and the development of heart failure in some DCM patients and therefore, the reliability of genetic counselling. However, LMNA mutations producing speckles result not only in nuclear envelope structural damage, but may also lead to the dysregulation of cellular functions controlled by sumoylation, such as transcription, chromosome organisation, and nuclear trafficking.

Animals↗

Clinical characteristics and methods of treatment of patients with stable coronary heart disease in the primary care settings--the results of the Polish, Multicentre Angina Treatment Pattern (ATP) study.

For further improvement of coronary heart disease (CHD) management large epidemiological studies are required to characterise the real population of patients with CHD, treated in the primary care settings, and to evaluate how the guidelines are implemented in the everyday clinical practice. The aim of the Angina Treatment Pattern (ATP) survey was to characterise (i) the population of patients, treated by the primary care physicians for stable CHD, (ii) the methods applied by the primary care physicians to establish diagnosis of CHD and (iii) the pharmacological therapies for CHD. Across Poland, 397 primary care physicians were randomly selected. They recruited 7420 patients (49% men; mean age, 62 +/- 10 years; range: 25-93 years), treated for stable CHD. The duration of CHD was 7.4 +/- 6.6 years (range: 6 months-50 years), 2750 (37%) patients had myocardial infarction. The following risk factors of CHD were present: arterial hypertension in 58%, dyslipidaemia in 52%, smoking in 40%, family history of CHD in 56% and obesity or overweight in 73% of patients. Primary care physicians based a diagnosis of CHD predominantly on a history of anginal pain (in 33% patients), accompanied either by abnormal resting ECG or positive exercise test (in additional 31% patients). Only in 5% of patients, coronary angiography was applied to diagnose CAD. The following groups of drugs have been used: long-acting nitrates in 90%, anti-platelet drugs or anti-coagulants in 71% (aspirin in 65%), angiotensin-converting enzyme inhibitors in 51%, beta-blockers in 48%, calcium antagonists 31%, hypolipaemic drugs in 23% (statins in 10%) and metabolic agents in 16% of patients. Despite an extensive use of classical anti-anginal drugs (including at least one of the following: long-acting nitrates, beta-blockers, calcium antagonists in 95% of patients), 85% of patients still complained of anginal symptoms. Neither prevalence of angina among patients nor nitroglycerin intake depended on the number of anti-anginal drugs taken (monotherapy vs. combination therapy: 82% vs. 86% and 4.9 vs. 5.3 doses weekly, respectively). Among the primary care physicians, the methods used to establish a CHD diagnosis and the mode of CHD management are far from optimal. The results of the ATP study confirm the need for further intensification of activities to improve the process of diagnosis and management among patients with CHD, treated by the family doctors.

Adolescent↗

Efficacy of trimetazidine in patients with recurrent angina: a subgroup analysis of the TRIMPOL II study.

OBJECTIVES: The revascularization procedures become more and more popular to treat coronary artery disease, in many countries. Some patients are free of angina after revascularization, without any documented re-stenosis present with recurrent angina symptoms after a period of time. The aim of this work was to assess the efficacy of trimetazidine in the subpopulation of patients with a history of PTCA or CABG, who were included in the TRIMPOL II study. METHODOLOGY: A subgroup of 94 patients was retrospectively analysed from the TRIMPOL II study, a multicentre, double-blind randomised placebo-controlled trial in 426 patients with stable effort angina. These patients have a history of revascularization for coronary artery disease, and they are still symptomatic after 6 months despite a treatment with metoprolol (50 mg twice daily). They were randomly allocated to receive either trimetazidine (20 mg 3 times daily) or placebo for 12 weeks, on top of the beta-blocker. Exercise test parameters, clinical efficacy and safety were assessed. Results were analysed using the Student test, the Mann-Whitney test or the Shapiro-Wilk test. RESULTS: Compared to placebo, the 12-week treatment with trimetazidine significantly improved: time to 1 mm ST segment depression (385.1 s +/- 144.6 s versus 465.0 s +/- 143.8 s [p < 0.01]); exercise test duration (466.9 s +/- 144.8 s versus 524.4 s +/- 131.5 s [p = 0.048]), total workload (9.0 m.e. +/- 2.4 m.e versus 10.1 m.e. +/- 2.4 m.e [p = 0.035]) as well as time to onset of angina (433.6 s +/- 164 s versus 508.1 s +/- 132.4 s [p = 0.031]). Weekly number of angina attacks and nitrate consumption were significantly reduced in the trimetazidine group when compared to placebo. Three mild gastro-intestinal side-effects were reported in the trimetazidine group. CONCLUSION: These results show that trimetazidine provides anti-anginal efficacy in post-revascularized patients with recurrent angina despite a monotherapy with metoprolol. The treatment was well accepted.

Adrenergic beta-Antagonists↗

Transvenous closure of moderate and large secundum atrial septal defects in adults using the Amplatzer septal occluder.

The aim was to determine the feasibility of using the Amplatzer septal occluder for closure of moderate and large secundum atrial septal defects in adults. Fifty patients aged 16-76 years (mean +/- SD, 40 +/- 15.5), underwent successful device implantation. Flow ratios of 1.4-8.5 (mean +/- SD, 2.6 +/- 1.6) were calculated. The defects were: centrally placed (n = 31), antero-superior with partial or total deficiency of aortic rim (n = 19), multiple (n = 3) and with aneurysmal septum (n = 23). They measured 4-25 mm (median 14) on echocardiography and balloon sized 7-31 mm (median 19.5). Devices of 7-34 mm (median 20) were implanted. Patient follow up for 1 month (50/50 patients), 3 months (40/50) and 12 months (13/50), achieved respective rates of 90%, 92% and 98% of complete occlusion. In one patient a transient atrioventricular block (2:1) developed, and one had a transient STT elevation. One female had an episode of 30 min loss of vision over the lateral aspect of the left eye 3 months after implantation. In conclusion, transvenous occlusion of secundum atrial septal defects with the Amplatzer septal occluder in adults is safe, and can be performed without significant complications. Large defects, defects with a very deficient or absent aortic rim, defects with an aneurysmal septum as well as some multiple defects can be closed with an almost 100% early complete occlusion rate. This makes the procedure an alternative to surgery for selected adult patients.

Adolescent↗

Transcatheter closure of a 16 mm hypertensive patent ductus arteriosus with the Amplatzer muscular VSD occluder.

There is little experience with transcatheter closure of very large, hypertensive patent ductus arteriosus. We present a case of successful closure of a 16 mm ductus with the Amplatzer VSD occluder, a device originally designed for transcatheter closure of congenital muscular ventricular septal defects. To our best knowledge this is the largest ductus ever closed by an interventional technique.

Adolescent↗

Efficacy and safety of dofetilide in the prevention of symptomatic episodes of paroxysmal supraventricular tachycardia: a 6-month double-blind comparison with propafenone and placebo.

BACKGROUND: Existing drug therapies for paroxysmal supraventricular tachycardia (PSVT) have potentially serious adverse effects. Dofetilide, a pure class III antiarrhythmic agent, may offer an effective and safe alternative for treating PSVT. This study compared the efficacy and safety of dofetilide with that of propafenone and placebo in the prevention of PSVT. METHODS: This multicenter, randomized, placebo-controlled, parallel-group study compared the effectiveness of oral dofetilide 500 microg given twice daily with that of propafenone 150 mg given 3 times a day and placebo in preventing the recurrence of PSVT in 122 symptomatic patients. Episodes of PSVT were documented by symptom diaries and Hertcard (Hertford Medical, Hertfordshire, UK) event recorders. RESULTS: After 6 months of treatment, patients taking dofetilide, propafenone, and placebo had a 50%, 54%, and 6% probability, respectively, of remaining free of episodes of PSVT (P <.001 for both dofetilide and propafenone vs placebo). Both dofetilide and propafenone also decreased the frequency of episodes of PSVT; the median numbers of episodes in the dofetilide- and propafenone-treated groups were 1 and 0.5, respectively, compared with 5 in the placebo-treated group. Dofetilide was well tolerated; no proarrhythmia occurred. Three patients taking propafenone had serious treatment-related adverse effects that required drug discontinuation. CONCLUSIONS: Dofetilide and propafenone were equally effective in preventing the recurrence of or decreasing the frequency of PSVT.

Administration, Oral↗

Clinical and therapeutic profile of patients presenting with acute coronary syndromes who do not have significant coronary artery disease.The Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) Trial Investigators.

BACKGROUND: A proportion of patients who present with suspected acute coronary syndrome (ACS) are found to have insignificant coronary artery disease (CAD) during coronary angiography, but these patients have not been well characterized. METHODS AND RESULTS: Of the 5767 patients with non-ST-segment elevation ACS who were enrolled in the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin (Eptifibatide) Therapy (PURSUIT) trial and who underwent in-hospital angiography, 88% had significant CAD (any stenosis >50%), 6% had mild CAD (any stenosis >0% to </=50%), and 6% had no CAD (no stenosis identified). The frequency of death or nonfatal myocardial infarction at 30 days was reduced with eptifibatide treatment in patients with significant CAD (18.3% versus 15.6% for placebo, P=0.006) but not in those with mild CAD (6.6% versus 5.4%, P=0.62) and with no CAD (3.0% versus 1. 2%, P=0.28). We identified independent baseline predictors of insignificant CAD (mild or no CAD) and used them to develop a simple predictive nomogram of the probability of insignificant CAD for use at hospital presentation. This nomogram was validated in a separate population of patients with non-ST-segment elevation ACS. CONCLUSIONS: Patients with suspected ACS found to have insignificant CAD have a low risk of adverse outcomes, do not appear to benefit from treatment with eptifibatide, and can be predicted with a simple nomogram drawn from baseline characteristics. Because patients with significant CAD appear to have an enhanced benefit from eptifibatide treatment, the predictive nomogram developed can be used to determine indications for glycoprotein IIb/IIIa blockade.

Acute Disease↗

Prior aspirin use predicts worse outcomes in patients with non-ST-elevation acute coronary syndromes. PURSUIT Investigators. Platelet IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy.

Aspirin is beneficial in the prevention and treatment of cardiovascular events, but patients who have events while taking aspirin may have worse outcomes than those not on aspirin. We investigated the association between prior aspirin use and clinical outcomes in 9,461 patients with non-ST-elevation acute coronary syndromes enrolled in the Platelet IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial, before and after adjustment for baseline factors. We also examined whether eptifibatide has a differential treatment effect in prior aspirin users. Prior aspirin users were less likely to have an enrollment myocardial infarction (MI) (vs unstable angina) (43.9% vs 48.8%, p = 0.001) but more likely to have death or MI at 30 days (16.1% vs 13.0%, p = 0.001) and at 6 months (19.9% vs 15.9%, p = 0.001). After adjustment, prior aspirin users remained less likely to have an enrollment MI (odds ratio 0.88, 95% confidence interval 0.79 to 0.97) and more likely to have death or MI at 30 days (odds ratio 1.16, 95% confidence interval 1.00 to 1.33) but not at 6 months (odds ratio 1.14, 95% confidence interval 0.98 to 1.33). In a multivariable model, eptifibatide did not have a different treatment effect in prior aspirin users compared with nonusers (p = 0.534). Prior aspirin users had fewer enrollment MIs but worse long-term outcomes than nonusers. We found no evidence for a different treatment effect of eptifibatide in prior aspirin users.

Acute Disease↗

Mechanical valve replacement in congenital heart disease in children.

BACKGROUND AND AIM OF THE STUDY: The study aim was to analyze predictive factors of long-term results after mechanical heart valve replacement in children. METHODS: Forty-four patients (19 males, 25 females; mean age 8.9+/-3.9 years, median 7.0 years, range: 1.3 to 15 years) underwent heart valve replacement with mechanical prostheses. Of these patients, 25 had left atrioventricular valve replacement (LavVR) (18 mitral, six tricuspid in corrected transposition of the great arteries (TGA), one common in a univentricular heart), 13 had aortic valve replacement (AVR) and six had tricuspid valve replacement (TVR). The etiology of the valvular disease was congenital in all patients, and complicated by infective endocarditis in seven (16%). Fifteen patients had undergone previous procedures and 16 required simultaneous repair of associated lesions. The mean size of the implanted prosthesis was 26 mm (range: 19-29 mm) for LavVR, 29.7 mm (range: 23-33 mm) for TVR, and 21.9 mm (range: 19-25 mm) for AVR. Postoperatively, all patients received oral anticoagulation. The mean follow up was 6.8+/-3.5 years (total 290 patient-years). RESULTS: There was no early mortality, but three patients (7%) died later; all late deaths occurred in patients with LavVR. There were two sudden deaths, both in patients with complex congenital heart disease and heart failure (before the ACE inhibitor era), and one valve-related death from thrombotic occlusion of a mitral prosthesis. Five patients were reoperated on; three for patient-prosthesis mismatch, one for periprosthetic leak, and one for aortic dissection due to Marfan's syndrome. Thrombotic obstruction occurred in three patients; two in the tricuspid position were treated successfully with thrombolysis, but one in the left atrioventricular position proved fatal. After seven years, the survival rate was 93.4%. CONCLUSIONS: Mechanical heart valve replacement in children aged over one year with congenital heart disease can be performed with satisfactory early and late results. Mechanical valves of >23 mm diameter in the atrioventricular position in the systemic ventricle, and >21 mm in the aortic orifice, can offer excellent long-lasting hemodynamic performance. However, mechanical valves in the tricuspid position are prone to develop thrombotic occlusion.

Adolescent↗

Long-term follow-up results of balloon valvuloplasty for congenital aortic stenosis: predictors of late outcome.

AIMS: Long-term follow-up of patients with aortic valve stenosis undergoing balloon valvuloplasty was evaluated with respect to survival, the need for repeat intervention and factors predicting late outcome. METHODS AND RESULTS: Forty-five patients between 3.5 to 23 years old (mean 11.7 +/- 4.5) were followed for 62 +/- 30 months (range 11-122). The transvalvar aortic gradient decreased from 84 +/- 20 to 36 +/- 10 mmHg (p < 0.001) and remained significantly lower (50 +/- 26 mmHg; p < 0.001) at follow-up. At that time, 10 patients (including 4 with significant valve incompetence) had gradients >/= 60 mmHg. The procedure resulted in significant valve incompetence (grade >/= 3) in 8 patients (17.8%). There was a progression of incompetence and 13 patients (28.9%) had significant regurgitation at follow-up. All survived. Fifteen patients (33.3%) required re-intervention 51 +/- 24 months after valvuloplasty. The indications were: aortic stenosis in 5 patients; regurgitation in 6 patients; and stenosis with regurgitation in 4 patients. Actuarial freedom from re-intervention at 2, 4, 6 and 8 years was 96%, 88%, 61% and 56% of patients, respectively. The residual post-valvuloplasty gradient was the only predictor of re-intervention for valve stenosis (odds ratio = 3.2 for every 10 mmHg gradient increase; p = 0.017). A residual post-valvuloplasty gradient >/= 40 mmHg increased the relative risk of re-intervention sixfold. The immediate post-valvuloplasty aortic regurgitation grade was the only risk factor of re-intervention for regurgitation (odds ratio = 34 for every incompetence degree increase; p = 0.0019). Incompetence grade >/= 2 increased the risk of re-intervention tenfold. CONCLUSIONS: Valvuloplasty carries the risk of development of valve incompetence, which progresses with time. Some patients develop restenosis. The </= 10 year survival after the procedure is excellent, and 56% of patients are free of re-intervention at 8 years. The immediate post-valvuloplasty incompetence grade and transvalvar gradient are the predictors of late re-intervention.

Adolescent↗

High-Pressure Bail-out Coronary Stenting Without Anticoagulation: Early Outcome and Follow-up Results.

PURPOSE:The purpose of this study is to assess the immediate outcome and long-term results of high pressure bail-out coronary stenting without subsequent anticoagulation. PATIENTS AND METHODS: Between June 1994 and September 1996, 32 consecutive patients (males 24, mean age 55 +/- 9.3 years) underwent bail-out stenting at a mean deployment pressure of 15.5 +/- 2.3 mmHg because of complicated PTCA. A total of 54 stents (Palmaz-Schatz, Micro, Gianturco Roubin and Wiktor) were implanted, from one to four stents into each vessel. After the procedure all patients were treated with ticlopidine 500 mg/day and acetylosalicylic acid 300 mg/day only. RESULTS: Stents were successfully delivered in all patients. In the cath lab procedural success was 96.9%. During the in-hospital phase, there was one (3.1%) acute stent thrombosis followed by urgent bypass surgery (CABG). Four (12.5%) non-Q wave myocardial infarctions occurred. There were no subacute stent thrombosis or hemorrhagic complications. Six month angiographic restudy in 28 patients showed restenosis in 13 (46.4%): 9 patients were treated successfully by rePTCA. At one year 13 (40.6%) major adverse cardiac events occurred: eleven (34.4%) target lesion revascularizations (9 PTCA, 2 CABG), one (3.1%) elective CABG surgery and one (3.1%) late cardiac death. Event-free survival was 93.8% at one month, 65.6% at six months, and 59.4% at one year. CONCLUSIONS: High pressure bail-out coronary stenting with antiplatelet regimen is an effective and safe procedure for treating complicated PTCA. Although the restenosis rate is high, in most cases in-stent restenosis can be treated by rePTCA. In 60% of patients clinical course at one year was uneventful.

Journal Article↗

Left ventricular enlargement is common in relatives of patients with dilated cardiomyopathy.

Idiopathic dilated cardiomyopathy is characterized by dilation and impaired contractility of one or both ventricles. Long-term prognosis is poor. Early diagnosis has the potential for substantial reduction of morbidity and mortality. Recent studies, based on echocardiographic assessment of relatives of the patients have shown that familial dilated cardiomyopathy is relatively common. The authors studied 215 relatives (mean age, 27 years; 111 male) of 38 index patients with idiopathic dilated cardiomyopathy by clinical examination, electrocardiography, and two-dimensional, M-mode and Doppler echocardiography. Seven relatives (3%) from six families were shown to have dilated cardiomyopathy. Thus, 6 of the 38 index patients (16%) had familial disease. Furthermore, left ventricular enlargement either during diastole or systole was found in 66 of 174 healthy relatives (38%). This is significantly more frequent than in our normal control population of 100 unrelated subjects studied in the same way (18%; P < .0001). These 66 relatives with left ventricular enlargement belonged to 27 of the 38 examined families (71%). Dilated cardiomyopathy was found to be familial in 16% of patients. Of the relatives examined, 41% had left ventricular abnormalities. These findings provide further evidence for a genetic background of dilated cardiomyopathy. Relatives with left ventricular enlargement may have an early stage and/or latent form of the disease.

Adult↗

Long term follow up after percutaneous mitral commissurotomy with the Inoue balloon-incidence of restenosis.

UNLABELLED: The long term outcome of 300 consecutive patients following percutaneous mitral commissurotomy (PMC) with the Inoue balloon was analyzed with regard to the incidence of restenosis. There were 256 females and 44 males (mean age 44.4 +/- 9.9 years, range 18-69 years), 52 had previous surgical commissurotomy, 96 were in atrial fibrillation, and 16 had a history of embolism. PCM was carried out with a success rate of 84% (no significant mitral regurgitation and mitral valve area (MVA) > 1.5 cm2). Two hundred and seventy patients were available for clinical and serial echocardiographic studies at six months, 12 months and once a year thereafter (18 patients operated on for mitral regurgitation less than six months after PMC, three patients lost to follow up, nine patients refused to return). MVA increased with PMC from 1.18 cm2 +/- 0.3 to 2.0 +/- 0.3 cm2 and then decreased to 1.8 +/- 0.3 at a mean follow up of 24.0 +/- 13.5 months (range 6-55). Echocardiographic restenosis (RS) (MVA at follow up < 1.5 cm2 with a 50% loss of the initial gain) was found in 38 patients (14%). Twenty-five (66%) of them remained in NYHA class I or II. Restenosis free survival according to the Kaplan-Mayer curve was 93%, 86%, 77% and 73% at 12,24,36 and 55 months respectively. None of the 24 clinical, hemodynamic, echocardiographic or procedural variables used on the Cox proportional hazard regression analysis identified predictors of restenosis free survival. CONCLUSIONS: The overall incidence of echocardiographic restenosis post PMC is low (12.6%) in patients followed for a mean period of two years and often occurs without worsened clinical symptoms. It may be difficult to define clinical, echocardiographic or procedural factors as significant predictors of restenosis free survival.

Adolescent↗

Percutaneous mitral commissurotomy with the Inoue balloon for severe mitral stenosis during pregnancy.

Percutaneous mitral commissurotomy using the Inoue balloon was performed in seven pregnant women between May 1990 and November 1991. The mean age of the group was 31.5 years (range 28-35 years). The mean gestation time was 29 weeks (range 20-38 weeks). All patients presented with severe symptoms; two had a recent history of pulmonary oedema, the rest exhibited marked shortness of breath, and mild exercise and paroxysmal nocturnal dyspnea. All were in sinus rhythm. Two patients had previously undergone closed mitral valvulotomy five and 14 years before their recent hospitalization. Echocardiographic examination revealed severe mitral stenosis, with the mitral valve area being less than 1.2 cm2 in all but one patient. None of the patients had left atrial thrombi or mitral regurgitation as seen on two-dimensional and Doppler echocardiography. Four patients (two with restenosis) had severe lesions of the subvalvular apparatus with thickening and marked shortening of the chordae, as assessed by echocardiography. Successful percutaneous mitral valvulotomy was completed in all seven patients using 25-28 mm Inoue balloons. There was one, transient maternal complications. Fetal complication did not occur. It is concluded that percutaneous, transseptal, mitral balloon valvulotomy during pregnancy with the Inoue balloon is a safe procedure, which can be recommended for suitable clinical cases.

Adult↗

Management of ventricular septal defect with associated aortic incompetence.

Twenty-two patients with a ventricular septal defect and aortic incompetence underwent surgical repair. Mean age was 9.6 years (range, 9 to 15 years). Mean follow-up was 32.4 +/- 15.8 months. The ventricular septal defect was perimembranous in 19 patients and doubly committed or juxtaarterial in 3. Most showed only a small left-to-right shunt. Mean diameter was 11.9 +/- 4.8 mm. Aortic incompetence was mild in 6 patients, moderate in 4, and severe in 12. In 16 patients closure of the ventricular septal defect and aortic valvoplasty were both performed through the aortic root. There were no deaths. All patients retained normal sinus rhythm. No complete heart block was found. In 3 patients secondary aortic valve replacement was required for severe incompetence; in 1 the cause was bacterial endocarditis, in another technical failure, and in a third progressive incompetence over an 8-month period. All patients showed substantial clinical improvement, marked decrease or disappearance of the valvar incompetence, diminution of the left ventricular end-diastolic diameter, and decreased cardiothoracic ratio. We conclude that primary repair is the operation of choice for this combination of lesions. This can avoid or delay considerably valvar replacement. The left-sided approach proves safe and is our preferred technique.

Abnormalities, Multiple↗