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Biomedical subjects

Michael Domanski

Publications and source records attributed to Michael Domanski.

15 recordsLinked to original sources
PubMed2006

Frequency of aspirin resistance in a community hospital.

Aspirin resistance and its predictors were studied in community hospital patients who required antiplatelet therapy for thrombotic event prophylaxis. Demographic and antiplatelet medication data were collected and medication response followed. Aspirin resistance was assayed with the VerifyNow System with > or = 550 aspirin reaction units (ARUs) used as a dichotomous indicator of aspirin resistance. Patients (n = 123) were 21 to 95 years old; 49.6% were women, 77.2% were black, 95.1% were hypertensive, 85.4% had coronary disease, and 30.1% were smokers. ARU score for 325 versus 81 mg/day was 435.2 +/- 93.7 versus 401.9 +/- 83.9 ARU (p = 0.04), with a 12.1% (8 of 66 patients) nonresponse rate to 81 mg/day. Of the 8 patients who were unresponsive to 81 mg/day of aspirin, 7 responded to 325 mg/day. The 5.3% (3 of 57 patients) who were resistant to 325 mg/day received clopidogrel; 2 became responders. Multivariate analysis demonstrated significant associations of aspirin resistance with smoking (risk ratio 11.47, 95% confidence interval 6.69 to 18.63, p < 0.0001), including a significant interaction between smoking and aspirin resistance. In conclusion, this study estimates aspirin resistance prevalence and shows a strong association of smoking with platelet hyperactivity in a diverse community hospital population. Nonresponders to 81 mg/day frequently responded to 325 mg/day or to the addition of clopidogrel.

Adult↗
PubMed2006

Renal function and effectiveness of angiotensin-converting enzyme inhibitor therapy in patients with chronic stable coronary disease in the Prevention of Events with ACE inhibition (PEACE) trial.

BACKGROUND: Patients with reduced renal function are at increased risk for adverse cardiovascular outcomes. In the post-myocardial infarction setting, angiotensin-converting enzyme (ACE) inhibitors have been shown to be as effective in patients with impaired renal function as in those with preserved renal function. METHODS AND RESULTS: We assessed the relation between renal function and outcomes, the influence of ACE inhibition on this relation, and whether renal function modifies the effectiveness of ACE inhibition in patients with stable coronary artery disease and preserved systolic function enrolled in the Prevention of Events with ACE inhibition trial (PEACE). Patients (n=8290) were randomly assigned to receive trandolapril (target, 4 mg/d) or placebo. Clinical creatinine measures were available for 8280 patients before randomization. The estimated glomerular filtration rate (eGFR) was calculated with the 4-point Modification of Diet in Renal Disease equation. Renal function was related to outcomes, and the influence of ACE-inhibitor therapy was assessed with formal interaction modeling. The mean eGFR in PEACE was 77.6+/-19.4, and 1355 (16.3%) patients had reduced renal function (eGFR <60 mg.mL(-1).1.73 m(-2)). We observed a significant interaction between eGFR and treatment group with respect to cardiovascular and all-cause mortality (P=0.02). Trandolapril was associated with a reduction in total mortality in patients with reduced renal function (adjusted HR, 0.73; 95% CI, 0.54 to 1.00) but not in patients with preserved renal function (adjusted HR, 0.94; 95% CI, 0.78 to 1.13). CONCLUSIONS: Although trandolapril did not improve survival in the overall PEACE cohort, in which mean eGFR was relatively high, trandolapril reduced mortality in patients with reduced eGFR. These data suggest that reduced renal function may define a subset of patients most likely to benefit from ACE-inhibitor therapy for cardiovascular protection.

Aged↗
PubMed2006

Diuretic use, progressive heart failure, and death in patients in the DIG study.

BACKGROUND: Nonpotassium-sparing diuretics (NPSDs), have been associated with increased sudden cardiac death (SCD) and progressive heart failure (HF) death in HF patients. METHODS AND RESULTS: In 6797 Digitalis Investigation Group study patients, risk ratios were calculated for death, cardiovascular death (CVD), death from worsening HF, SCD, and HF hospitalization among those taking a potassium-sparing (PSD), NPSD, or no diuretic. Compared with not taking diuretic, risk of death (relative risk [RR] 1.36, 95% confidence interval [CI] 1.17-1.59, P < .0001), CVD (RR = 1.38, 95% CI 1.17-1.63, P = .0001), progressive HF death (RR = 1.41, 95% CI 1.06-1.89, P = .02), SCD (RR = 1.67, 95% CI 1.23-2.27, P = .001), and HF hospitalization (RR = 1.68, 95% CI 1.41-1.99, P < .0001) were increased with NPSD. There was no significant difference in any end point for patients taking only PSD compared to no diuretic. PSD only subjects were less likely than NPSD subjects to be hospitalized for HF (RR = 0.71, 95% CI 0.52-0.96, P = .02). CONCLUSION: NPSDs are associated with increased risk of death, CVD, progressive HF death, SCD, and HF hospitalization. A randomized trial is needed to assess the role of NPSDs versus PSDs in HF patients.

Aged↗
PubMed2005

Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure.

BACKGROUND: Sudden death from cardiac causes remains a leading cause of death among patients with congestive heart failure (CHF). Treatment with amiodarone or an implantable cardioverter-defibrillator (ICD) has been proposed to improve the prognosis in such patients. METHODS: We randomly assigned 2521 patients with New York Heart Association (NYHA) class II or III CHF and a left ventricular ejection fraction (LVEF) of 35 percent or less to conventional therapy for CHF plus placebo (847 patients), conventional therapy plus amiodarone (845 patients), or conventional therapy plus a conservatively programmed, shock-only, single-lead ICD (829 patients). Placebo and amiodarone were administered in a double-blind fashion. The primary end point was death from any cause. RESULTS: The median LVEF in patients was 25 percent; 70 percent were in NYHA class II, and 30 percent were in class III CHF. The cause of CHF was ischemic in 52 percent and nonischemic in 48 percent. The median follow-up was 45.5 months. There were 244 deaths (29 percent) in the placebo group, 240 (28 percent) in the amiodarone group, and 182 (22 percent) in the ICD group. As compared with placebo, amiodarone was associated with a similar risk of death (hazard ratio, 1.06; 97.5 percent confidence interval, 0.86 to 1.30; P=0.53) and ICD therapy was associated with a decreased risk of death of 23 percent (0.77; 97.5 percent confidence interval, 0.62 to 0.96; P=0.007) and an absolute decrease in mortality of 7.2 percentage points after five years in the overall population. Results did not vary according to either ischemic or nonischemic causes of CHF, but they did vary according to the NYHA class. CONCLUSIONS: In patients with NYHA class II or III CHF and LVEF of 35 percent or less, amiodarone has no favorable effect on survival, whereas single-lead, shock-only ICD therapy reduces overall mortality by 23 percent.

Aged↗
PubMed2005

Heart Failure with Preserved Systolic Function.

At least 30% of patients with congestive heart failure have preserved systolic function in the absence of significant valvular heart disease. These patients have diastolic dysfunction. Patients are frequently older and hypertensive. The rate of hospitalization in these patients is similar to that in patients with systolic dysfunction. Mortality is intermediate between that of patients with systolic dysfunction heart failure and normal subjects. Diagnosis requires a clear demonstration of the presence of the heart failure syndrome, normal systolic function, and the absence of valvular disease that could increase left atrial pressures. The diagnosis is supported by evidence of diastolic dysfunction that, from a practical point of view, will be provided most frequently by tissue Doppler imaging. Few randomized data are available on efficacy of therapeutic approaches. Acute treatment centers on reducing central blood volume with diuretics and nitrates and controlling heart rate, particularly in the setting of atrial fibrillation. Further treatment centers on reversing underlying pathophysiologic changes, particularly left ventricular hypertrophy. Control of hypertension and antagonism of the renin-angiotensin-aldosterone system appear to be promising therapeutic approaches.

Journal Article↗
PubMed2004

Coupling of folding and binding of thymosin beta4 upon interaction with monomeric actin monitored by nuclear magnetic resonance.

Thymosin beta4 is a major actin-sequestering protein, yet the structural basis for its biological function is still unknown. This study provides insight regarding the way this 43-amino acid peptide, mostly unstructured in solution, binds to monomeric actin and prevents its assembly in filaments. We show here that the whole backbone of thymosin beta4 is highly affected upon binding to G-actin. The assignment of all amide protons and nitrogens of thymosin in the bound state, obtained using a combination of NMR experiments and selective labelings, shows that thymosin folds completely upon binding and displays a central extended region flanked by two N- and C-terminal helices. The cleavage of actin by subtilisin in the DNase I binding loop does not modify the structure of thymosin beta4 in the complex, showing that the backbone of the peptide is not in close proximity to segment 42-47 of actin. The combination of our NMR results and previously published mutation and cross-link data allows a better characterization of the binding mode of thymosins on G-actin.

Actins↗
PubMed2004

Geographic variability in patient characteristics, treatment and outcome in an International Trial of Magnesium in acute myocardial infarction.

BACKGROUND: The interpretation of clinical trials and efforts directed at reducing the worldwide burden of coronary disease must take regional differences into account. This study examined the regional differences in baseline characteristics, treatment, and outcome in patients presenting with ST elevation myocardial infarction (STEMI) who were entered into the Magnesium in Coronaries (MAGIC) trial. METHODS AND RESULTS: MAGIC randomized 6213 patients to standard care with either placebo infusion or infusion of intravenous magnesium sulphate. There was no difference in mortality between these groups. For this analysis, three geographic regions were identified (Region 1=United States and Canada; Region 2=Bulgaria, Georgia, and Russia; Region 3=Austria, Belgium, Chile, Hungary, Israel, the Netherlands, New Zealand, and Venezuela) and compared with respect to baseline characteristics, treatment, and 30-day mortality. Patients in Region 2 had the highest prevalence of adverse risk factors at entry, including history of prior myocardial infarction, heart failure, stroke, and hypertension; anterior location of index acute myocardial infarction; and presence of pulmonary congestion at presentation. Furthermore, Region 2 patients infrequently received reperfusion therapy compared with those in Region 1. Region 3 was intermediate in this regard. Mortality was highest in Region 2, least in Region 1, and intermediate in Region 3. CONCLUSION: Geographic location, particularly, parts of Eastern Europe, is strongly and independently associated with mortality following STEMI. This geographic variation in mortality confirms prior reports, although adequate explanations continue to be elusive and are beyond the scope of this large simple trial. Future international trials must recognize this variation in design, analysis, and interpretation.

Aged↗
PubMed2004

Prevalence and predictors of heart failure with preserved systolic function: community hospital admissions of a racially and gender diverse elderly population.

BACKGROUND: The reported prevalence of preserved systolic function (PSF) heart failure (HF) varies widely and has not been well-studied in nonwhite patients. To estimate the prevalence of PSF HF resulting in hospital admission, we studied admissions to a large community hospital serving a racially diverse community. METHODS: The charts of 300 consecutive patients > or =65 years old with a primary discharge diagnosis of HF were reviewed. In patients who met the Framingham criteria for HF diagnosis, an assessment of left ventricular function was obtained from review of chart data. Comparison of baseline characteristics and multivariate analysis of potential predictors of PSF HF was undertaken. RESULTS: Of the 300 patients, 247 (82%) met the Framingham criteria for diagnosis of HF. Ninety-seven patients (39%) of these had PSF. Twenty (8%) of the diagnosed HF patients had a diagnosis of severe aortic or mitral valvular disease, 9 of whom had preserved systolic functions. Thus 88 (36%) of the HF patients had PSF HF likely resulting from diastolic dysfunction. On multivariate analysis, age, hypertension at presentation, peripheral edema, normal sinus rhythm and a history of coronary artery bypass grafting or coronary angioplasty were significantly associated with PSF HF rather than HF with reduced systolic function. Left bundle branch block or other intraventricular conduction delay was independently associated with reduced systolic function HF. However, because these findings occurred in patients with and without systolic dysfunction, none were pathognomonic of PSF HF. CONCLUSION: In this racially diverse, majority nonwhite, cohort of older patients admitted for HF, the Framingham criteria for the diagnosis of HF were met in 82% of the patients. Of these, 39% had PSF HF and 36% had PSF HF in the absence of severe aortic or mitral valve disease, suggesting that diastolic dysfunction was etiologic. Although there was an independent association of PSF HF with a number of clinical characteristics, none of these characteristics was pathognomonic of preserved, versus reduced, systolic function HF.

Aged↗
PubMed2003

The effect of diabetes on outcomes of patients with advanced heart failure in the BEST trial.

OBJECTIVES: This was a retrospective analysis to determine the effect of diabetes on outcome in patients with advanced heart failure (HF), and to determine the effect of beta-blockade in patients with HF with and without diabetes mellitus. BACKGROUND: In chronic HF the impact on clinical outcomes and therapeutic response of the prevalent comorbid condition diabetes mellitus has not been extensively investigated. METHODS: We assessed the impact of diabetes on prognosis and effectiveness of beta-blocker therapy with bucindolol in patients with HF enrolled in the Beta-Blocker Evaluation of Survival Trial (BEST). We conducted a retrospective analysis to examine the prognosis of patients with advanced HF with and without diabetes, and the effect of beta-blocker therapy on mortality and HF progression or myocardial infarction (MI). The database was the 2,708 patients with advanced HF (36% with diabetes and 64% without diabetes) who were randomized to the beta-blocker bucindolol or placebo in BEST and followed for mortality, hospitalization, and MI for an average of two years. RESULTS: Patients with diabetes had more severe chronic HF and more coronary risk factors than patients without diabetes. Diabetes was independently associated with increased mortality in patients with ischemic cardiomyopathy (adjusted hazard ratio 1.33, 95% confidence interval 1.12 to 1.58, p = 0.001), but not in those with a nonischemic etiology (adjusted hazard ratio 0.98, 95% confidence interval 0.74 to 1.30, p = 0.89). Compared with patients without diabetes, in diabetic patients beta-blocker therapy was at least as effective in reducing death or HF hospitalizations, total hospitalizations, HF hospitalizations, and MI. Ventricular function and physiologic responses to beta-blockade were similar in patients with and without diabetes. CONCLUSIONS: Diabetes worsens prognosis in patients with advanced HF, but this worsening appears to be limited to patients with ischemic cardiomyopathy. In advanced HF beta-blockade is effective in reducing major clinical end points in patients with and without diabetes.

Adrenergic beta-Antagonists↗
PubMed2003

Diuretic use, progressive heart failure, and death in patients in the Studies Of Left Ventricular Dysfunction (SOLVD).

OBJECTIVES: We sought to determine whether non-potassium-sparing diuretics (PSDs) in the absence of a PSD may result in progressive heart failure (HF). BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors incompletely suppress ACE activity in HF patients. Furthermore, non-PSDs are activators of aldosterone secretion. We reasoned that non-PSDs, in the absence of a PSD, might result in progressive HF. METHODS: In the 6,797 patients in the Studies Of Left Ventricular Dysfunction (SOLVD), we compared the risk of hospitalization for, or death from, HF between those taking a PSD and those who were not, adjusting for known covariates. RESULTS: The risk of hospitalization from worsening HF in those taking a PSD relative to those taking only a non-PSD was 0.74 (95% confidence interval [CI] 0.55 to 0.99; p = 0.047). The relative risk for cardiovascular death was 0.74 (95% CI 0.59 to 0.93; p = 0.011), for death from all causes 0.73 (95% CI 0.59 to 0.90; p = 0.004), and for hospitalization for, or death from, HF 0.75 (95% CI 0.58 to 0.97; p = 0.030). Compared with patients not taking any diuretic, the risk of hospitalization or death due to worsening HF in patients taking non-PSDs alone was significantly increased (risk ratio [RR] = 1.31, 95% CI 1.09 to 1.57; p = 0.0004); this was not observed in patients taking PSDs with or without a non-PSD (RR = 0.99, 95% CI 0.76 to 1.30; p = 0.95). CONCLUSIONS: The use of PSDs in HF patients is associated with a reduced risk of death from, or hospitalization for, progressive HF or all-cause or cardiovascular death, compared with patients taking only a non-PSD.

Aged↗
PubMed2003

Angiographic changes in saphenous vein grafts are predictors of clinical outcomes.

BACKGROUND: Previous studies have suggested that angiographic evidence of disease progression in coronary arteries increases the risk of subsequent coronary clinical events. This study ascertained whether patients enrolled in the Post Coronary Artery Bypass Graft Clinical Trial (POST CABG) who had substantial progression of atherosclerosis in >or=1 saphenous vein grafts (on the basis of assessment of baseline and follow-up angiograms obtained 4-5 years after study entry), but who had not reported clinical symptoms before follow-up angiography, were at a higher risk of subsequent events than patients who did not have substantial progression of atherosclerosis (decrease >or=0.6 mm in lumen diameter at site of greatest change from baseline). METHODS: All 1351 patients enrolled in the trial underwent baseline angiography; only the 961 patients who had follow-up angiography and no coronary events before the follow-up study were included in this analysis. The clinical center staff contacted patients to ascertain the events that had occurred after follow-up angiography (approximately 3.4 years later). RESULTS: Sixty-nine patients had died; 870 patients or relatives were interviewed, and 22 patients could not be contacted. Univariable estimates of relative risk associated with substantial progression ranged from 2.2 (P <.001) for cardiovascular death or nonfatal myocardial infarction to 3.3 (P <.001) for revascularization. Multivariable and univariable estimates of risk were similar. CONCLUSIONS: The findings provide evidence that patients who had substantial progression of atherosclerosis in vein grafts are at an increased risk for subsequent coronary events and suggest that angiographic changes in vein grafts are appropriate surrogate measures for clinical outcomes.

Aged↗
PubMedDate not supplied

Pulse pressure and cardiovascular disease-related mortality: follow-up study of the Multiple Risk Factor Intervention Trial (MRFIT).

CONTEXT: The sixth Joint National Committee (JNC-VI) classification system of blood pressure emphasizes both systolic blood pressure (SBP) and diastolic blood pressure (DBP) for cardiovascular disease risk assessment. Pulse pressure may also be a valuable risk assessment tool. OBJECTIVE: To compare relationships of SBP, DBP, and pulse pressure, separately and jointly, with cardiovascular disease-related mortality in men. DESIGN AND SETTING: Data from the Multiple Risk Factor Intervention Trial (MRFIT), which screened men aged 35 to 57 years from 1973 through 1975 at 22 US centers, was used to assess cardiovascular disease-related mortality through 1996. PARTICIPANTS: A total of 342 815 men without diabetes or a history of myocardial infarction were divided into 2 groups based on their age at MRFIT screening (35- to 44-year-olds and 45- to 57-year olds). Participant blood pressure levels were classified into a JNC-VI blood pressure category based on SBP and DBP (optimal, normal but not optimal, high normal, stage 1 hypertension, stage 2-3 hypertension), and pulse pressure was calculated. MAIN OUTCOME MEASURE: Cardiovascular disease-related mortality. RESULTS: There were 25 721 cardiovascular disease-related deaths. Levels of SBP and DBP were more strongly related to cardiovascular disease than pulse pressure. Relationships of SBP, DBP, and pulse pressure to cardiovascular disease-related mortality varied within JNC-VI category. Concordant elevations of SBP and DBP were associated with a greater risk of cardiovascular disease-related mortality for both age groups of men. Among men aged 45 to 57 years, higher SBP and lower DBP (discordant elevations) also yielded a greater risk of cardiovascular disease-related mortality. CONCLUSION: In both age groups, cardiovascular disease risk assessment was improved by considering both SBP and DBP, not just SBP, DBP, or pulse pressure separately.

Adult↗