Chronic kidney disease as a cardiovascular risk factor.
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Cardiovascular Diseases↗
Biomedical subjects
David R Holmes
Publications and source records attributed to David R Holmes.
Frequency, patient characteristics, and outcomes of mild-to-moderate heart failure complicating ST-segment elevation acute myocardial infarction: lessons from 4 international fibrinolytic therapy trials.
BACKGROUND: There is a paucity of data on the incidence of mild-to-moderate heart failure (HF) complicating ST-segment elevation acute myocardial infarction (MI) and its impact on short-term outcomes. Our objective was to determine the incidence, timing, and consequences of mild-to-moderate HF complicating acute MI. METHODS: We examined the occurrence of death or death/recurrent MI (re-MI) in patients enrolled in the Global Utilization of Streptokinase and Tissue-Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I), the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO IIb), the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO-III), and Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT-II) trials, which examined different fibrinolytic therapies for MI. We excluded patients who had cardiogenic shock (n = 2994) or unknown HF status at all time points (n = 13,716). Of the remaining 61,041 patients, 17,949 patients (29.4%) had HF, 1566 (8.7%) only at baseline, 10,339 (57.6%) only after admission, and 6044 (33.7%) at baseline and after. RESULTS: The incidence of HF was 32.5% in the United States and 26.9% elsewhere. At 30 days, death and death/re-MI occurred in 2% and 4% of patients without HF and 8% and 12% of patients with HF, respectively (2% and 4% of patients with HF only at baseline, 7% and 13% of patients with HF only after baseline, and 10% and 13% of patients with HF at baseline and later). By use of multivariable analyses, the presence of HF was associated with 1.55 times greater risk of dying at 30 days (95% CI 1.38-1.74) and 2.15 times greater risk of death/re-MI (95% CI 1.96-2.36). CONCLUSION: Mild-to-moderate HF is a frequent and ominous complication of MI, especially when it does not resolve or develops after admission.
Clinical Trials as Topic↗
Low-risk percutaneous coronary interventions without on-site cardiac surgery: two years' observational experience and follow-up.
BACKGROUND: We studied the safety and efficacy of performing low-risk elective and acute infarct percutaneous coronary interventions at a community hospital without cardiac surgical capability. METHODS: Immanuel St Joseph's Hospital is located 85 miles from St Mary's Hospital, which is the nearest center with on-site cardiac surgery. All components of the Mayo Clinic percutaneous coronary intervention program were replicated at Immanuel St Joseph's Hospital, including a telemedicine system to enable real-time consultation with interventional and cardiac surgical colleagues during procedures. RESULTS: From March 1999 to June 2001, 196 patients underwent elective percutaneous coronary intervention at Immanuel St Joseph's Hospital. Procedural success was achieved in 195 (99.5%) patients, with 1 (0.5%) inhospital death. At mean follow-up of 8.2 months, 2 (1.0%) additional patients died of noncardiac causes and 15 (7.7%) patients required target vessel revascularization. From March 2000 to June 2001, 89 patients underwent primary percutaneous coronary intervention for acute myocardial infarction. Procedural success was achieved in 83 (93.3%) patients, with 3 (3.4%) inhospital deaths. At 30-day follow up, no additional patients died, had recurrent myocardial infarction, or required target vessel revascularization. No patients required transfer to another facility for emergent cardiac surgery for a procedure-related complication. CONCLUSIONS: Low-risk elective and acute infarct percutaneous coronary interventions can be performed with safety and efficacy at a community hospital without cardiac surgical capability by following rigorous standards.
Aged↗
Risk stratification and interventional cardiology: Robert L. Frye Lecture.
Risk stratification and risk-benefit ratios are extremely important in guiding patient-physician interactions as well as patient and family counseling. Risks associated with percutaneous transluminal coronary angioplasty are (1) compromise of the vessel lumen or vessel integrity, (2) unsuccessful procedure, and (3) restenosis. Predicting mortality risk depends on the specific patient population to be treated and on the specific mortality model used. The most common models are those from New York State, the American College of Cardiology, the Northern New England Cooperative Group, the University of Michigan, and The Cleveland Clinic Foundation. As more data and sophisticated analyses become available, risk stratification will become more accurate as long as the approach used is straightforward, makes intuitive sense, and is easy and efficient to apply.
Acute Kidney Injury↗
Cardiogenic shock: a lethal complication of acute myocardial infarction.
Cardiogenic shock is a serious complication of myocardial infarction (MI) that affects approximately 7% of MI patients, accounting for the majority of all deaths related to acute infarction. Shock is typically the result of a massive amount of damage to the left ventricular myocardium; its defining characteristics are hypotension (systolic blood pressure [SBP] of 90 mm Hg or less, or in chronically hypertensive patients a drop in SBP of 30 mm Hg or more) and hypoperfusion. Shock occurs more frequently in ST-segment elevation MI (STEMI) patients than in non-STEMI patients. Revascularization, either with angioplasty or coronary bypass graft surgery, is associated with better outcomes than intensive medical therapy in patients with shock. Adjunctive therapies include vasopressor therapy, mechanical ventilatory support, and intra-aortic balloon pump counterpulsation (IABP). IABP can stabilize some patients and may make revascularization safer. Other adjunctive therapies being investigated include improved mechanical support devices, induction of systemic hypothermia, use of supersaturated oxygen, and, as medical therapy, administration of L-NMMA.
Humans↗
Coronary intervention in thrombus-rich lesions: beyond stents and glycoprotein IIb/IIIa inhibitors.
Despite widespread use of stents and GP IIb/IIIa antagonists, complications following percutaneous treatment of thrombus-rich lesions continue to plague patients with ACS. In these patients the angiographically evident coronary thrombosis may represent a high degree of thrombus burden, which leads to a higher level of microembolization and its clinical sequelae. New catheter-based thrombus burden reduction systems and distal protection devices show promise for improving the prognosis of these high risk patients by decreasing distal microembolization, and thereby preventing myonecrosis. Careful procedural timing and patient selection are also likely to improve outcomes and resource utilization in the management of ACS patients.
Angioplasty, Balloon, Coronary↗
Increased ubiquitin immunoreactivity in unstable atherosclerotic plaques associated with acute coronary syndromes.
OBJECTIVES: The current study was designed to examine whether ubiquitin expression is higher in unstable than in stable lesions of patients with acute coronary syndrome (ACS). BACKGROUND: The ubiquitin system has been identified as the nonlysosomal pathway of protein degradation; it is involved in a number of biologic processes crucial to cell and tissue integrity and therefore, might be potentially involved in the rupture of unstable coronary plaques. METHODS: We conducted an autopsy-based study of 25 consecutive patients with fatal ACS. Lesions of both infarct-related and noninfarct-related segments from the same patients were examined for the expression and localization of ubiquitin by use of immunohistochemistry and a semiquantitative grading scale. RESULTS: Ubiquitin immunoreactivity was higher in infarct-related than in noninfarct-related lesions (1.4 +/- 0.5 vs. 1.1 +/- 0.6, p = 0.03). Compared with areas adjacent to the plaque (0.6 +/- 0.7), ubiquitin immunoreactivity was higher in areas around the lipid core (2.5 +/- 0.8, p < 0.001), plaque shoulders (1.6 +/- 1.1, p < 0.001), and fibrous cap regions (1.6 +/- 1.1, p < 0.001). Within the plaque area, co-localization of ubiquitin immunoreactivity with T cells and macrophages was found. In areas adjacent to the plaque, ubiquitin immunoreactivity co-localized with neointima cells and media smooth muscle cells. CONCLUSIONS: In patients with ACS, ubiquitin immunoreactivity is enhanced in unstable, infarct-related lesions, predominantly in plaque regions of tissue degradation. Based on these findings, this study suggests a role for the ubiquitin system in the destabilization and rupture of coronary atherosclerotic plaques in humans.
Acute Disease↗
Comparison of in-hospital and one-year outcomes in patients with and without diabetes mellitus undergoing percutaneous catheter intervention (from the National Heart, Lung, and Blood Institute Dynamic Registry).
Extrapolation of improvements in percutaneous coronary intervention (PCI) and outcomes to patients with diabetes has not been systematically examined in clinical practice. Two waves of consecutive patients (n = 4,629) who underwent PCI from July 1997 to June 1999 enrolled in the National Heart, Lung, and Blood Institute Dynamic Registry comprise the study population. There were 1,058 patients with treated diabetes and 3,571 patients without clinically evident diabetes. As a group, patients with diabetes tended to have more clinical, angiographic, and procedural risk factors. Although crude in-hospital mortality rates were higher in patients with diabetes (diabetics 2.3%, nondiabetics 1.3%; p = 0.02), the adjusted risk of in-hospital death (odds ratio 1.46, 95% confidence interval [CI] 0.80 to 2.66) was not significantly different. At 1 year, patients with diabetes had a significantly higher adjusted risk of mortality (risk ratio [RR] 1.80, 95% CI 1.35 to 2.41) and need for repeat revascularization (RR 1.40, 95% CI 1.13 to 1.74). There was a significant interaction between stent use and diabetic status with the need for repeat revascularization (adjusted RR in nondiabetics 0.73, 95% CI 0.61 to 0.88; adjusted RR in patients with diabetes 1.20, 95% CI 0.88 to 1.65). Beta blockers at the time of hospital discharge were significantly associated with reduced mortality rates at 1 year in both groups.
Age Factors↗
Frequency and correlates of coronary stent thrombosis in the modern era: analysis of a single center registry.
OBJECTIVES: The study examined the frequency, correlates, and outcome of patients with stent thrombosis within 30 days of stent placement. BACKGROUND: Patients in trials evaluating stents or dual antiplatelet therapy to prevent coronary stent thrombosis have generally had narrow inclusion criteria; the extent to which stent thrombosis rates in such trials represent current practice, particularly with the availability of newer stents, is unclear. METHODS: We performed a retrospective analysis of the Mayo Clinic Percutaneous Coronary Intervention database and identified all patients who received at least one coronary stent and dual antiplatelet therapy (aspirin and ticlopidine or clopidogrel for two to four weeks). RESULTS: Four thousand five hundred nine patients underwent successful coronary stent implantation and were treated with dual antiplatelet therapy between July 1, 1994, and April 30, 2000. Stent thrombosis occurred in 23 patients (0.51%; 95% confidence interval 0.32%, 0.76%) within 30 days of stent placement. Multivariate analysis using bootstrap model selection to avoid over-fitting the model indicated that only the number of stents placed was an independent correlate of stent thrombosis (odds ratio 1.80, p < 0.001). The frequency of death and frequency of nonfatal myocardial infarction (MI) among the 23 patients with stent thrombosis were 48% and 39%, respectively. CONCLUSIONS: Stent thrombosis is even more rare in the current era than in earlier trials. Number of stents placed was an independent correlate of stent thrombosis. Most patients who suffer stent thrombosis either die or suffer MI.
Aged↗
C-reactive protein relaxes human vessels in vitro.
OBJECTIVE: C-reactive protein (CRP) is a sensitive marker of inflammation and a prognostic marker in cardiovascular disease. Evidence suggests direct biological activities of CRP within the vascular wall. The study was designed to examine the vasoreactive effects of CRP. METHODS AND RESULTS: Human internal mammary artery rings were obtained during cardiovascular bypass surgery and suspended in an organ bath chamber. The rings were precontracted with endothelin-1, and response to cumulative concentrations of CRP was obtained. Experiments were repeated after initial incubation with 20, 40, and 60 mmol/L KCl, the potassium channel blockers BaCl, tetraethylammonium chloride, and glibenclamide, and the NO synthase inhibitor N-monomethyl-L-arginine and also after removal of the endothelium. CRP caused dose-dependent relaxation of human internal mammary artery rings, which was not affected by preincubation with N-monomethyl-L-arginine or removal of the endothelium. Maximum relaxation response to CRP (79.5+/-10%) was attenuated by KCl (2.5+/-11.5%, P<0.001), BaCl (24.5+/-7.5%, P<0.001), and tetraethylammonium chloride (34.9+/-8.25%, P<0.01) but not by glibenclamide. Conclusions- The present study demonstrates that CRP exerts an endothelium-independent vasorelaxing effect via potassium channels. Thus, the study suggests a role of CRP in the regulation of vascular tone.
Aged↗
Long-term outcome of patients treated with repeat percutaneous coronary intervention after failure of gamma-brachytherapy for the treatment of in-stent restenosis.
BACKGROUND: Although (192)Ir intracoronary brachytherapy has been demonstrated to dramatically reduce the recurrence of in-stent restenosis, up to 24% of these patients will still require repeat target-vessel revascularization. The short- and long-term outcomes of repeat percutaneous intervention in this population have not been characterized. METHODS AND RESULTS: Analysis was performed of all patients enrolled in the GAMMA-I and GAMMA-II brachytherapy trials who underwent repeat percutaneous target lesion revascularization (TLR) because of restenosis. Subjects were divided into 2 cohorts: those who had received (192)Ir brachytherapy and those randomized to placebo. Forty-five (17.6%) of a total of 256 patients whose index treatment was intracoronary radiation therapy and 36 (29.8%) of 121 patients whose index treatment was placebo required repeat percutaneous TLR. The mean time to this first TLR was 295+/-206 days in the irradiated group and 202+/-167 days in the placebo group (P=0.03). Acute procedural success occurred in 100% of irradiated patients and 94% of placebo controls (P=0.19). After the first TLR, a subsequent TLR was required in 15 (33.3%) of 45 brachytherapy patients versus 17 (47.2%) of 36 placebo failure patients (P=0.26). There was no significant difference in time to second TLR between the 2 groups. Other long-term major adverse event rates in both groups were comparable to those of other contemporary angioplasty/stenting series. CONCLUSIONS: In those patients who "fail" (192)Ir intracoronary brachytherapy for in-stent restenosis, treatment with (192)Ir delays the time to first TLR. Additionally, repeat percutaneous intervention in these patients is safe and efficacious in the short term, with acceptable long-term results.
Angioplasty, Balloon, Coronary↗
Results of Prevention of REStenosis with Tranilast and its Outcomes (PRESTO) trial.
BACKGROUND: Restenosis after percutaneous coronary intervention (PCI) is a major problem affecting 15% to 30% of patients after stent placement. No oral agent has shown a beneficial effect on restenosis or on associated major adverse cardiovascular events. In limited trials, the oral agent tranilast has been shown to decrease the frequency of angiographic restenosis after PCI. METHODS AND RESULTS: In this double-blind, randomized, placebo-controlled trial of tranilast (300 and 450 mg BID for 1 or 3 months), 11 484 patients were enrolled. Enrollment and drug were initiated within 4 hours after successful PCI of at least 1 vessel. The primary end point was the first occurrence of death, myocardial infarction, or ischemia-driven target vessel revascularization within 9 months and was 15.8% in the placebo group and 15.5% to 16.1% in the tranilast groups (P=0.77 to 0.81). Myocardial infarction was the only component of major adverse cardiovascular events to show some evidence of a reduction with tranilast (450 mg BID for 3 months): 1.1% versus 1.8% with placebo (P=0.061 for intent-to-treat population). The primary reason for not completing treatment was > or =1 hepatic laboratory test abnormality (11.4% versus 0.2% with placebo, P<0.01). In the angiographic substudy composed of 2018 patients, minimal lumen diameter (MLD) was measured by quantitative coronary angiography. At follow-up, MLD was 1.76+/-0.77 mm in the placebo group, which was not different from MLD in the tranilast groups (1.72 to 1.78+/-0.76 to 80 mm, P=0.49 to 0.89). In a subset of these patients (n=1107), intravascular ultrasound was performed at follow-up. Plaque volume was not different between the placebo and tranilast groups (39.3 versus 37.5 to 46.1 mm(3), respectively; P=0.16 to 0.72). CONCLUSIONS: Tranilast does not improve the quantitative measures of restenosis (angiographic and intravascular ultrasound) or its clinical sequelae.
Administration, Oral↗
Was your mother right--do we always need to close the door?
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Age Factors↗
Prognostic implications of abnormalities in renal function in patients with acute coronary syndromes.
BACKGROUND: Outcomes in patients with mild to moderate renal function (RF) abnormalities presenting with acute coronary syndromes (ACS) are not well defined. METHODS AND RESULTS: A convenience sample of 4 ACS trial databases including all enrolled patients was assessed to determine 30- and 180-day outcomes. The 4 trials were Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) IIb, GUSTO-III, Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT), and Platelet IIb/IIIa Antagonism for the Reduction of Acute coronary syndrome events in a Global Organization Network (PARAGON-A). Patients were stratified into ST-segment elevation (STE) and non-ST-segment elevation (NSE) groups and by the presence or absence of abnormal RF (creatinine clearance <70 mL/min). In the STE group, 7670 of 18 621 patients (41%) had abnormal RF. In the NSE group, 8152 of 19 304 (42%) had abnormal RF. Patients with abnormal RF were older, more often female, and more likely to have adverse baseline characteristics. They had higher mortality and higher mortality/nonfatal myocardial infarction (MI) at both 30 and 180 days, regardless of ST-segment status. Creatinine clearance was independently associated with risk of mortality (hazard ratio 0.79 in the STE group and 0.81 in the NSE group) and with risk of mortality/MI (hazard ratio 0.93) in the NSE group at 180 days. CONCLUSIONS: Patients presenting with ACS frequently have abnormal RF. Abnormal RF is a marker of adverse baseline clinical characteristics and is independently associated with increased risk of death and death/MI.
Acute Disease↗
Low-output, low-gradient aortic stenosis in patients with depressed left ventricular systolic function: the clinical utility of the dobutamine challenge in the catheterization laboratory.
BACKGROUND: Although aortic valve replacement can be performed at an acceptable risk level in selected patients with left ventricular systolic dysfunction and low-output, low-gradient aortic stenosis, not all patients presenting with these hemodynamics will benefit from the operation. Some patients may have only mild aortic stenosis, despite a small calculated valve area. We report on the clinical utility of diagnostic dobutamine stimulation during cardiac catheterization in these diagnostically challenging patients. METHODS AND RESULTS: Thirty-two patients with low-output, low-gradient aortic stenosis and an ejection fraction <40% had dobutamine infusion in the catheterization laboratory. On the basis of the results of the dobutamine test, 21 patients underwent aortic valve replacement. All patients with a final aortic valve area < or =1.2 cm2 at peak dobutamine infusion and a mean gradient of >30 mm Hg were found to have severe calcific aortic stenosis at operation. In the 15 patients in whom contractile reserve was identified during dobutamine challenge (increase in stroke volume >20%), 1 patient died perioperatively (7% mortality) and 12 patients were alive in New York Heart Association class I or II status at follow-up. CONCLUSIONS: In patients with left ventricular systolic dysfunction and aortic stenosis with a low output and a low mean gradient, dobutamine challenge may aid in selecting those who would benefit from an aortic valve operation.
Adrenergic beta-Agonists↗
Correlates of procedural complications and a simple integer risk score for percutaneous coronary intervention.
OBJECTIVES: Our goals were to identify clinical and angiographic risk factors associated with major cardiovascular complications of percutaneous coronary intervention (PCI) (in-hospital death, Q-wave myocardial infarction, urgent or emergent coronary artery bypass surgery and stroke) and to construct a simple score for risk stratification. BACKGROUND: Both clinical and angiographic features influence risk of PCIs. METHODS: Percutaneous coronary interventions performed between January 1, 1996, and December 31, 1999, were analyzed. Logistic regression and bootstrap methods were used to create an integer risk score for estimating the risk of procedural complications using baseline, angiographic and procedural characteristics. The risk score was tested in a validation-set consisting of all procedures performed in the year 2000. RESULTS: Among 5,463 procedures, 5 clinical and 3 angiographic variables were significantly correlated with procedural complications: cardiogenic shock, left main coronary artery disease, severe renal disease, urgent or emergent procedure, congestive heart failure class III or higher, thrombus, multivessel disease and older age. In the validation-set, the model fitted the data adequately; the average receiver operating characteristic curve area was 0.782 (standard deviation, 0.018). CONCLUSIONS: Eight variables were combined into a convenient bedside risk scoring system that estimates the risk of complications after PCIs.
Aged↗
Simvastatin preserves myocardial perfusion and coronary microvascular permeability in experimental hypercholesterolemia independent of lipid lowering.
UNLABELLED: OBJECTIVES; This study was designed to assess the lipid-independent effects of simvastatin on myocardial perfusion (MP) and coronary microvascular permeability index (PI) at baseline and during episodes of increased cardiac demand in experimental hypercholesterolemia. BACKGROUND: Simvastatin preserves coronary endothelial function in experimental hypercholesterolemia independent of its lipid-lowering effect. However, the functional significance of this observation is unknown. METHODS: Pigs were randomized to three groups: normal diet (N), high-cholesterol diet (HC) and HC diet plus simvastatin (HC+S) for 12 weeks. Subsequently, cardiac electron beam computed tomography was performed before and during intravenous infusion of adenosine and dobutamine, and MP and PI were calculated. RESULTS: Total and low density lipoprotein cholesterol levels were similarly and significantly increased in HC and HC+S animals compared with N. Basal MP was similar in all groups. Myocardial perfusion significantly increased in response to either adenosine or dobutamine in N and HC+S animals. Dobutamine also significantly increased MP in HC animals. However, the changes of MP in response to either drug were significantly lower in the HC group compared with the other two groups (p < 0.01 for adenosine and p < 0.05 for dobutamine vs. N and HC+S). Basal PI was similar in all groups and was not altered by either drug in N and HC+S animals. In contrast, PI significantly increased in HC pigs during infusion of either adenosine (p < 0.001) or dobutamine (p < 0.05). CONCLUSIONS: These findings demonstrate that chronic administration of simvastatin preserves myocardial perfusion response and coronary microvascular integrity during cardiac stress in experimental hypercholesterolemia independent of lipid lowering.
Animals↗
Outcomes in diabetics undergoing revascularization: the long and the short of it.
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Angioplasty, Balloon, Coronary↗