Background Although beta‐blockers are recommended following myocardial infarction (MI), the benef... more Background Although beta‐blockers are recommended following myocardial infarction (MI), the benefits of long‐term treatment have not been established. The study's aim was to evaluate beta‐blocker efficacy by dose in 1‐year post‐MI survivors. Methods and Results The OBTAIN (Outcomes of Beta‐Blocker Therapy After Myocardial Infarction) registry included 7057 patients with acute MI, with 6077 one‐year survivors. For this landmark analysis, beta‐blocker dose status was available in 3004 patients and analyzed by use (binary) and dose at 1 year after MI. Doses were classified as no beta‐blocker and >0% to 12.5%, >12.5% to 25%, >25% to 50%, and >50% of target doses used in randomized clinical trials. Age was 63 to 64 years, and approximately two thirds were men. Median follow‐up duration was 1.05 years (interquartile range, 0.98–1.22). When analyzed dichotomously, beta‐blocker therapy was not associated with improved survival. When analyzed by dose, propensity score analysi...
Laboratory investigation; a journal of technical methods and pathology, 1976
Tissue factor content of WISH amnion cells in spinner culture increases 3- to 10-fold within 12 h... more Tissue factor content of WISH amnion cells in spinner culture increases 3- to 10-fold within 12 hours after subculture, then declines to a basal level within 30 to 50 hours. Maximal development of activity requires fresh serum and fresh medium. When added at the time of subculture, actinomycin D and cycloheximide completely inhibit development of coagulant activity; when added several hours after transfer, these inhibitors suppress the development but do not affect the disappearance of activity. Of the oxidative phosphorylation inhibitors tested, dinitrophenol had no effect whereas carbonyl cyanide m-chlorophenylhydrazone inhibited the activity increase but did not alter the decline. The kinetics of development and decay are similar over a pH range of 6.7 to 7.6 and with fetal calf serum concentration between 5 and 30 per cent. At pH 6.7 or in 30 per cent fetal calf serum, cell division did not occur. 3H-leucine and 35SO4= incorporation into the cell surface coat did not change appr...
Laboratory investigation; a journal of technical methods and pathology, 1976
Tissue factor activity in suspension cultures of WISH amnion cells is modulated by pharmacologic ... more Tissue factor activity in suspension cultures of WISH amnion cells is modulated by pharmacologic doses of agents which alter membrane structure and function. Lysosomal stabilizing steroids (hydrocortisone, dexamethasone, aldosterone, prednisolone, and estradiol) suppress the change in activity which follows subculture; lytic steroids (testosterone and progesterone) are ineffective. Chloroquine both increases the specific activity and extends the time before return to the basal level. Dimethyl sulfoxide and ouabain suppress the complete expression of activity but do not inhibit the subsequent decay. The effect of cytochalasin B is complex, the drug being either suppressive or slightly stimulatory depending on the time of addition. Cyclic nucleotides (AMP or GMP) or insulin do not regulate the expression of tissue factor in these cells. A dramatic increment and prolongation of activity occurs when colchicine or vinblastine is added to the cell suspension shortly after subculture; ther...
Restenosis after coronary angioplasty occurs in at least 30% of patients in the first six months ... more Restenosis after coronary angioplasty occurs in at least 30% of patients in the first six months and, as yet, there is no known treatment to decrease this event. We tested a monoclonal antibody Fab fragment (c7E3) directed against the platelet glycoprotein IIb/IIIa integrin, the receptor mediating the final common pathway of platelet aggregation, to see whether it reduced the frequency of clinical restenosis. Patients who had unstable angina, recent or evolving myocardial infarction, or high-risk angiographic morphology, were randomised to receive c7E3 bolus and a 12 hour infusion of c7E3 (708 patients), c7E3 bolus and placebo infusion (695 patients), or placebo bolus and placebo infusion (696 patients). With maintenance of the double-blind state, patients were followed-up for at least 6 months to determine the need for repeat angioplasty or surgical coronary revascularisation and the occurrence of ischaemic events. By 30 days, 12.8% of placebo bolus/placebo infusion patients had had a major ischaemic event (death, myocardial infarction, urgent revascularisation), compared with 8.3% of c7E3 bolus/c7E3 infusion patients, yielding a 4.5% difference (35% reduction, p = 0.008). At 6 months, the absolute difference in patients with major ischaemic event or elective revascularisation was 8.1% between placebo bolus/placebo infusion and c7E3 bolus/c7E3 infusion patients (35.1% vs 27.0%; 23% reduction p = 0.001). The favourable long-term effect was mainly due to less need for bypass surgery or repeat angioplasty in patients with an initial successful procedure, since need for repeat target vessel revascularisation was 26% less for c7E3 bolus/c7E3 infusion than for placebo treatment (16.5% vs 22.3%; p = 0.007). The c7E3 bolus/placebo infusion group had an intermediate outcome which was not significantly better than that of the placebo bolus/placebo infusion group. These results extend the benefit of c7E3 bolus/c7E3 infusion from reducing abrupt closure and acute-phase adverse outcomes to a diminished need for subsequent coronary revascularisation procedures. Because this therapy carries a risk of bleeding complications and has been studied only in high-risk angioplasty patients, further evaluation is needed before it can be applied to other patient groups.
European heart journal. Acute cardiovascular care, 2013
The cardiac intensive care unit (CICU) has evolved into a complex patient-care environment with e... more The cardiac intensive care unit (CICU) has evolved into a complex patient-care environment with escalating acuity and increasing utilization of advanced technologies. These changing demographics of care may require greater clinical expertise among physician providers. Despite these changes, little is known about present-day staffing practices in US CICUs. We conducted a survey of 178 medical directors of ICUs caring for cardiac patients to assess unit structure and physician staffing practices. Data were obtained from 123 CICUs (69% response rate) that were mostly from academic medical centres. A majority of hospitals utilized a dedicated CICU (68%) and approximately half of those hospitals employed a 'closed' unit model. In 46% of CICUs, an intensivist consult was available, but not routinely involved in care of critically ill cardiovascular patients, while 11% did not have a board-certified intensivist available for consultation. Most CICU directors (87%) surveyed agreed t...
Our understanding of the pathophysiology of acute coronary syndromes (ACS) has now been substanti... more Our understanding of the pathophysiology of acute coronary syndromes (ACS) has now been substantiated by many studies showing that atherothrombosis plays a predominant role. This article reviews the molecular interactions in thrombosis that may serve as therapeutic targets for more effective management of these syndromes. In particular, the discovery of the fact that the glycoprotein (GP) IIb-IIIa receptor plays a central and common role in platelet-mediated thrombosis has focused the therapeutic efforts. Blockade of this receptor has emerged as a new and potent strategy for inhibition of platelet aggregation and thus of clot formation. A number of trials have now corroborated the need for such antithrombotic drugs in the management of patients with non-ST-segment elevation ACS.
Our results indicate the following. 1. HRV is markedly depressed in inducible SCD survivors, a gr... more Our results indicate the following. 1. HRV is markedly depressed in inducible SCD survivors, a group at high risk of a subsequent episode of SCD. 2. Studies on patients who developed SCD during Holter monitoring indicate that HRV is depressed prior to SCD. 3. HRV is markedly depressed in inducible "asymptomatic ventricular ectopy" patients, with the degree of reduction paralleling that observed in inducible SCD survivors. In contrast, HRV of noninducible "asymptomatic ventricular ectopy" patients did not differ statistically from normal. 4. The findings provide additional evidence that cardiac parasympathetic function is depressed in patients prone to development of SCD and that altered autonomic function contributes to the development of electrical instability in such individuals. This accords with findings that such risk factors for sudden death as coronary artery disease, myocardial infarction, congestive failure, and hypertension all have been associated with reduced parasympathetic activity or attenuation of parasympathetically mediated reflexes. It is tempting to believe that diminished cardiac parasympathetic activity, perhaps by failing to counter excess sympathetic activity, contributes to SCD. 5. It may be inferred that HRV measurements have potential for serving as an independent predictor of inducibility in response to programmed ventricular stimulation and that they could represent a noninvasive screen for patients referred for evaluation of risk of SCD because of asymptomatic ventricular ectopy or other causes. In a larger sense, the data suggest that HRV measurements may provide information pertinent to the identification of individuals at increased risk of SCD that is independent of that provided by other risk factors. Given the human and economic stakes, further study is clearly warranted.
The authors studied the overall accuracy of planar and SPECT Tl imaging in the diagnosis of coron... more The authors studied the overall accuracy of planar and SPECT Tl imaging in the diagnosis of coronary artery disease (CAD) in 85 subjects (65 males, 20 females; 52 with angiographic CAD, 33 without CAD), and then separately analyzed men and women to see if factors such as breast attenuation significantly alter the accuracy. All subjects were exercised to symptom-limit or peak heart rate achievement, and injected with 2 mCi Tl-201. Planar and SPECT stress studies were acquired in a random order, with delayed studies acquired 3 hours after injection. The studies were viewed in a blinded, random order, and interpreted on a 5 point scale by consensus of 3 observers (1: definitely normal, 2: probably normal, 3: equivocal, 4: probably abnormal, 5: definitely abnormal). Receiver operating characteristic (ROC) curves were constructed for overall planar and SPECT, and then separately for male planar, male SPECT, female planar, female SPECT. The overall SPECT curve was above the overall planar...
Background Although beta‐blockers are recommended following myocardial infarction (MI), the benef... more Background Although beta‐blockers are recommended following myocardial infarction (MI), the benefits of long‐term treatment have not been established. The study's aim was to evaluate beta‐blocker efficacy by dose in 1‐year post‐MI survivors. Methods and Results The OBTAIN (Outcomes of Beta‐Blocker Therapy After Myocardial Infarction) registry included 7057 patients with acute MI, with 6077 one‐year survivors. For this landmark analysis, beta‐blocker dose status was available in 3004 patients and analyzed by use (binary) and dose at 1 year after MI. Doses were classified as no beta‐blocker and >0% to 12.5%, >12.5% to 25%, >25% to 50%, and >50% of target doses used in randomized clinical trials. Age was 63 to 64 years, and approximately two thirds were men. Median follow‐up duration was 1.05 years (interquartile range, 0.98–1.22). When analyzed dichotomously, beta‐blocker therapy was not associated with improved survival. When analyzed by dose, propensity score analysi...
Laboratory investigation; a journal of technical methods and pathology, 1976
Tissue factor content of WISH amnion cells in spinner culture increases 3- to 10-fold within 12 h... more Tissue factor content of WISH amnion cells in spinner culture increases 3- to 10-fold within 12 hours after subculture, then declines to a basal level within 30 to 50 hours. Maximal development of activity requires fresh serum and fresh medium. When added at the time of subculture, actinomycin D and cycloheximide completely inhibit development of coagulant activity; when added several hours after transfer, these inhibitors suppress the development but do not affect the disappearance of activity. Of the oxidative phosphorylation inhibitors tested, dinitrophenol had no effect whereas carbonyl cyanide m-chlorophenylhydrazone inhibited the activity increase but did not alter the decline. The kinetics of development and decay are similar over a pH range of 6.7 to 7.6 and with fetal calf serum concentration between 5 and 30 per cent. At pH 6.7 or in 30 per cent fetal calf serum, cell division did not occur. 3H-leucine and 35SO4= incorporation into the cell surface coat did not change appr...
Laboratory investigation; a journal of technical methods and pathology, 1976
Tissue factor activity in suspension cultures of WISH amnion cells is modulated by pharmacologic ... more Tissue factor activity in suspension cultures of WISH amnion cells is modulated by pharmacologic doses of agents which alter membrane structure and function. Lysosomal stabilizing steroids (hydrocortisone, dexamethasone, aldosterone, prednisolone, and estradiol) suppress the change in activity which follows subculture; lytic steroids (testosterone and progesterone) are ineffective. Chloroquine both increases the specific activity and extends the time before return to the basal level. Dimethyl sulfoxide and ouabain suppress the complete expression of activity but do not inhibit the subsequent decay. The effect of cytochalasin B is complex, the drug being either suppressive or slightly stimulatory depending on the time of addition. Cyclic nucleotides (AMP or GMP) or insulin do not regulate the expression of tissue factor in these cells. A dramatic increment and prolongation of activity occurs when colchicine or vinblastine is added to the cell suspension shortly after subculture; ther...
Restenosis after coronary angioplasty occurs in at least 30% of patients in the first six months ... more Restenosis after coronary angioplasty occurs in at least 30% of patients in the first six months and, as yet, there is no known treatment to decrease this event. We tested a monoclonal antibody Fab fragment (c7E3) directed against the platelet glycoprotein IIb/IIIa integrin, the receptor mediating the final common pathway of platelet aggregation, to see whether it reduced the frequency of clinical restenosis. Patients who had unstable angina, recent or evolving myocardial infarction, or high-risk angiographic morphology, were randomised to receive c7E3 bolus and a 12 hour infusion of c7E3 (708 patients), c7E3 bolus and placebo infusion (695 patients), or placebo bolus and placebo infusion (696 patients). With maintenance of the double-blind state, patients were followed-up for at least 6 months to determine the need for repeat angioplasty or surgical coronary revascularisation and the occurrence of ischaemic events. By 30 days, 12.8% of placebo bolus/placebo infusion patients had had a major ischaemic event (death, myocardial infarction, urgent revascularisation), compared with 8.3% of c7E3 bolus/c7E3 infusion patients, yielding a 4.5% difference (35% reduction, p = 0.008). At 6 months, the absolute difference in patients with major ischaemic event or elective revascularisation was 8.1% between placebo bolus/placebo infusion and c7E3 bolus/c7E3 infusion patients (35.1% vs 27.0%; 23% reduction p = 0.001). The favourable long-term effect was mainly due to less need for bypass surgery or repeat angioplasty in patients with an initial successful procedure, since need for repeat target vessel revascularisation was 26% less for c7E3 bolus/c7E3 infusion than for placebo treatment (16.5% vs 22.3%; p = 0.007). The c7E3 bolus/placebo infusion group had an intermediate outcome which was not significantly better than that of the placebo bolus/placebo infusion group. These results extend the benefit of c7E3 bolus/c7E3 infusion from reducing abrupt closure and acute-phase adverse outcomes to a diminished need for subsequent coronary revascularisation procedures. Because this therapy carries a risk of bleeding complications and has been studied only in high-risk angioplasty patients, further evaluation is needed before it can be applied to other patient groups.
European heart journal. Acute cardiovascular care, 2013
The cardiac intensive care unit (CICU) has evolved into a complex patient-care environment with e... more The cardiac intensive care unit (CICU) has evolved into a complex patient-care environment with escalating acuity and increasing utilization of advanced technologies. These changing demographics of care may require greater clinical expertise among physician providers. Despite these changes, little is known about present-day staffing practices in US CICUs. We conducted a survey of 178 medical directors of ICUs caring for cardiac patients to assess unit structure and physician staffing practices. Data were obtained from 123 CICUs (69% response rate) that were mostly from academic medical centres. A majority of hospitals utilized a dedicated CICU (68%) and approximately half of those hospitals employed a 'closed' unit model. In 46% of CICUs, an intensivist consult was available, but not routinely involved in care of critically ill cardiovascular patients, while 11% did not have a board-certified intensivist available for consultation. Most CICU directors (87%) surveyed agreed t...
Our understanding of the pathophysiology of acute coronary syndromes (ACS) has now been substanti... more Our understanding of the pathophysiology of acute coronary syndromes (ACS) has now been substantiated by many studies showing that atherothrombosis plays a predominant role. This article reviews the molecular interactions in thrombosis that may serve as therapeutic targets for more effective management of these syndromes. In particular, the discovery of the fact that the glycoprotein (GP) IIb-IIIa receptor plays a central and common role in platelet-mediated thrombosis has focused the therapeutic efforts. Blockade of this receptor has emerged as a new and potent strategy for inhibition of platelet aggregation and thus of clot formation. A number of trials have now corroborated the need for such antithrombotic drugs in the management of patients with non-ST-segment elevation ACS.
Our results indicate the following. 1. HRV is markedly depressed in inducible SCD survivors, a gr... more Our results indicate the following. 1. HRV is markedly depressed in inducible SCD survivors, a group at high risk of a subsequent episode of SCD. 2. Studies on patients who developed SCD during Holter monitoring indicate that HRV is depressed prior to SCD. 3. HRV is markedly depressed in inducible "asymptomatic ventricular ectopy" patients, with the degree of reduction paralleling that observed in inducible SCD survivors. In contrast, HRV of noninducible "asymptomatic ventricular ectopy" patients did not differ statistically from normal. 4. The findings provide additional evidence that cardiac parasympathetic function is depressed in patients prone to development of SCD and that altered autonomic function contributes to the development of electrical instability in such individuals. This accords with findings that such risk factors for sudden death as coronary artery disease, myocardial infarction, congestive failure, and hypertension all have been associated with reduced parasympathetic activity or attenuation of parasympathetically mediated reflexes. It is tempting to believe that diminished cardiac parasympathetic activity, perhaps by failing to counter excess sympathetic activity, contributes to SCD. 5. It may be inferred that HRV measurements have potential for serving as an independent predictor of inducibility in response to programmed ventricular stimulation and that they could represent a noninvasive screen for patients referred for evaluation of risk of SCD because of asymptomatic ventricular ectopy or other causes. In a larger sense, the data suggest that HRV measurements may provide information pertinent to the identification of individuals at increased risk of SCD that is independent of that provided by other risk factors. Given the human and economic stakes, further study is clearly warranted.
The authors studied the overall accuracy of planar and SPECT Tl imaging in the diagnosis of coron... more The authors studied the overall accuracy of planar and SPECT Tl imaging in the diagnosis of coronary artery disease (CAD) in 85 subjects (65 males, 20 females; 52 with angiographic CAD, 33 without CAD), and then separately analyzed men and women to see if factors such as breast attenuation significantly alter the accuracy. All subjects were exercised to symptom-limit or peak heart rate achievement, and injected with 2 mCi Tl-201. Planar and SPECT stress studies were acquired in a random order, with delayed studies acquired 3 hours after injection. The studies were viewed in a blinded, random order, and interpreted on a 5 point scale by consensus of 3 observers (1: definitely normal, 2: probably normal, 3: equivocal, 4: probably abnormal, 5: definitely abnormal). Receiver operating characteristic (ROC) curves were constructed for overall planar and SPECT, and then separately for male planar, male SPECT, female planar, female SPECT. The overall SPECT curve was above the overall planar...
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