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Biomedical subjects

Eric Boersma

Publications and source records attributed to Eric Boersma.

At least 19 recordsLinked to original sources
PubMed2025

Genome-wide association study meta-analysis provides insights into the etiology of heart failure and its subtypes.

Heart failure (HF) is a major contributor to global morbidity and mortality. While distinct clinical subtypes, defined by etiology and left ventricular ejection fraction, are well recognized, their genetic determinants remain inadequately understood. In this study, we report a genome-wide association study of HF and its subtypes in a sample of 1.9 million individuals. A total of 153,174 individuals had HF, of whom 44,012 had a nonischemic etiology (ni-HF). A subset of patients with ni-HF were stratified based on left ventricular systolic function, where data were available, identifying 5,406 individuals with reduced ejection fraction and 3,841 with preserved ejection fraction. We identify 66 genetic loci associated with HF and its subtypes, 37 of which have not previously been reported. Using functionally informed gene prioritization methods, we predict effector genes for each identified locus, and map these to etiologic disease clusters through phenome-wide association analysis, network analysis and colocalization. Through heritability enrichment analysis, we highlight the role of extracardiac tissues in disease etiology. We then examine the differential associations of upstream risk factors with HF subtypes using Mendelian randomization. These findings extend our understanding of the mechanisms underlying HF etiology and may inform future approaches to prevention and treatment.

Humans↗
PubMed2004

Differential treatment benefit of platelet glycoprotein IIb/IIIa inhibition with percutaneous coronary intervention versus medical therapy for acute coronary syndromes: exploration of methods.

BACKGROUND: Although many believe that platelet glycoprotein IIb/IIIa inhibitors should be used only in acute coronary syndrome patients undergoing percutaneous coronary intervention, supporting data from randomized clinical trials are tenuous. The assumption that these agents are useful only in conjunction with percutaneous coronary intervention is based primarily on inappropriate subgroup analyses performed across the glycoprotein IIb/IIIa inhibitor trials. METHODS AND RESULTS: We describe the problems with these analytical techniques and demonstrate that different approaches to the question can result in opposing answers. CONCLUSIONS: Clinical-practice decisions and practice guidelines should be based on overall trial results and not analyses of post-randomization subgroups.

Acute Disease↗
PubMed2004

Association between long-term statin use and mortality after successful abdominal aortic aneurysm surgery.

PURPOSE: To assess the potential long-term beneficial effects of statin use after successful abdominal aortic surgery. METHODS: Between 1991 and 2001, 570 patients underwent abdominal aortic aneurysm repair at the Erasmus Medical Center. Of the 519 patients (91%) who survived surgery beyond 30 days, 510 (98%) were followed for a median of 4.7 years (interquartile range, 2.7 to 7.3 years). These patients were evaluated for use of statins and beta-blockers, and for clinical risk factors (e.g., advanced age; prior myocardial infarction; diabetes mellitus; renal dysfunction; chronic pulmonary disease; history of heart failure, stroke, or angina), and their association with all-cause and cardiovascular mortality. RESULTS: A total of 205 patients (40%) died during follow-up; 140 due to cardiovascular causes. The incidence of all-cause (18% [27/154] vs. 50% [178/356], P <0.001) and cardiovascular (11% [17/154] vs. 34% [122/356], P <0.001) mortality was significantly lower in statin users than in nonstatin users. After adjusting for clinical risk factors and beta-blocker use, the association between statin use and reduced all-cause (hazard ratio [HR] = 0.4; 95% confidence interval [CI]: 0.3 to 0.6; P <0.001) and cardiovascular (HR = 0.3; 95% CI: 0.2 to 0.6; P <0.001) mortality persisted. Beta-blocker use was also associated with a significant reduction in all-cause (HR = 0.6; 95% CI: 0.5 to 0.9; P = 0.003) and cardiovascular (HR = 0.7; 95% CI: 0.4 to 0.9; P = 0.03) mortality. There was no evidence of an association between statin use and all-cause and cardiovascular mortality according to beta-blocker use or clinical risk factors. CONCLUSION: Long-term statin use is associated with reduced all-cause and cardiovascular mortality irrespective of clinical risk factors and beta-blocker use.

Adrenergic beta-Antagonists↗
PubMed2004

Incidence of recovery of contractile function following revascularization in patients with ischemic left ventricular dysfunction.

Contractile function in patients with ischemic left ventricular (LV) dysfunction may improve after myocardial revascularization. Currently, the incidence of contractile function recovery after revascularization in these patients is unclear. The aim of this study was to assess the incidence of function improvement after myocardial revascularization in patients with ischemic LV dysfunction. A total of 258 consecutive patients (aged 59 +/- 12 years) with severely depressed LV ejection fractions (EFs) due to chronic coronary artery disease and heart failure symptoms were studied. All patients underwent radionuclide ventriculography and 2-dimensional echocardiography at rest before and 3 to 6 months after revascularization. At baseline, 1,330 segments (32%) were normal and 2,775 segments (68%) were dysfunctional. Improvement after revascularization occurred in 736 of the 2,775 dysfunctional segments (27%). Overall, LVEF improved from 29 +/- 7 to 32 +/- 9 (p <0.0001). A clinically significant improvement of LVEF (>/=5% postrevascularization) was present in 101 patients (39%). Improvement of LVEF after revascularization was frequently observed in patients with a more severely impaired baseline LVEF. At least 3 segments with improvement of function were needed for an improvement of LVEF of >/=5%.

Coronary Artery Disease↗
PubMed2004

Aortic stenosis: an underestimated risk factor for perioperative complications in patients undergoing noncardiac surgery.

PURPOSE: To determine the incidence of perioperative events in patients with aortic stenosis undergoing noncardiac surgery. METHODS: We studied 108 patients with moderate (mean gradient, 25 to 49 mm Hg) or severe (mean gradient, > or =50 mm Hg) aortic stenosis and 216 controls who underwent noncardiac surgery between 1991 and 2000 at Erasmus Medical Center. Controls were selected based on calendar year and type of surgery. Details of clinical risk factors, type of surgery, and perioperative management were retrieved from medical records. The main outcome measure was the composite of perioperative mortality and nonfatal myocardial infarction. RESULTS: There was a significantly higher incidence of the composite endpoint in patients with aortic stenosis than in patients without aortic stenosis (14% [15/108] vs. 2% [4/216], P <0.001). This rate of perioperative complications was also substantially higher in patients with severe aortic stenosis compared with patients with moderate aortic stenosis (31% [5/16] vs. 11% [10/92], P = 0.04). After adjusting for cardiac risk factors, aortic stenosis remained a strong predictor of the composite endpoint (odds ratio = 5.2; 95% confidence interval: 1.6 to 17.0). CONCLUSION: Aortic stenosis is a risk factor for perioperative mortality and nonfatal myocardial infarction, and the severity of aortic stenosis is highly predictive of these complications.

Adult↗
PubMed2004

Why do patients with ischemic cardiomyopathy and a substantial amount of viable myocardium not always recover in function after revascularization?

OBJECTIVE: In patients with ischemic cardiomyopathy and a substantial amount of dysfunctional but viable myocardium, myocardial revascularization may improve left ventricular ejection fraction. The aim of this study was to evaluate why not all patients with a substantial amount of viable tissue recover in function after revascularization. METHODS: A total of 118 consecutive patients with a depressed left ventricular ejection fraction (on average 29% +/- 6%) due to chronic coronary artery disease underwent myocardial revascularization. Before revascularization all patients underwent dobutamine stress echocardiography to assess regional dysfunction, left ventricular volumes, and myocardial viability as well as radionuclide ventriculography to determine the left ventricular ejection fraction. Next, 3 to 6 months after revascularization, the left ventricular ejection fraction and regional contractile function were reassessed. Improvement of left ventricular ejection fraction > or = 5% following revascularization was considered clinically significant. RESULTS: Dobutamine stress echocardiography revealed that 489 (37%) of the 1329 dysfunctional segments were viable. A total of 61 (52%) patients had a substantial amount of viable myocardium (> or = 4 viable segments). In these 61 patients the global function was expected to recover > or = 5% after revascularization. However, left ventricular ejection fraction did not improve in 20 (33%) of 61 patients despite the presence of substantial viability. Clinical characteristics and echocardiographic data were comparable between patients with and without improvement. However, patients without improvement had considerably larger end systolic volumes (153 +/- 41 mL vs 133 +/- 46 mL, P =.007). The likelihood of recovery of global function decreased proportionally with the increase of end systolic volume (P <.001, R = 0.43, n = 61). Receiver operating characteristic curve analysis demonstrated that an end systolic volume > or = 140 mL had the highest sensitivity/specificity to predict the absence of global recovery. CONCLUSIONS: In patients with ischemic cardiomyopathy not only the amount of dysfunctional but viable myocardium but also the extent of left ventricular remodeling determines the improvement in function following myocardial revascularization. Patients with a high end systolic volume due to left ventricular remodeling have a decreased likelihood of improvement of global function.

Aged↗
PubMed2004

Site-specific intracoronary delivery of octreotide in humans: a pharmacokinetic study to determine dose-efficacy in restenosis prevention.

Somatostatin analogues have been shown to inhibit smooth muscle cell proliferation after local administration in vivo in animal models and in vitro using human coronary smooth muscle cell cultures. However, the optimal dosage for attaining effective site-specific administration remains undefined. This study was performed to determine the required theoretical dose of the somatostatin analogue, octreotide, to be delivered site specifically, for prevention of restenosis after coronary angioplasty in humans using a previously described methodology to determine regional pharmacokinetics of site-specific intracoronary administrated compounds. In 7 patients, 111In-octreotide, a gamma-labeled somatostatin analogue, was infused post angioplasty at the site of dilatation via a coil-balloon and quantified using a radio-isotopic technique. Efficiency of delivery ranged from 0.1% to 2.7% of the total infused dose of 0.18 microg, corresponding to a mean peak delivered amount of 1.8 +/- 1.9 ng. Total locally bioavailable 111In-octreotide reached 2.28 +/- 2.15 ng h. Based on current in vitro bioavailability and peak concentration data to inhibit proliferation and thymidine incorporation in human coronary smooth muscle cells, a 4000x higher averaged dose (approximately 700 microg) should be infused site specifically to obtain a biologic efficacy in 50% of the treated patients (ED50). Quantification of regional pharmacokinetics enables the determination of a theoretical site-specific dose for achieving appropriate bioavailability above the therapeutic threshold concentration for smooth muscle cell inhibition. This approach is proposed for the determination of the appropriate site-specific coronary infusion dose for the inhibition of restenosis after balloon angioplasty.

Angina, Unstable↗
PubMed2003

Left ventricular dyssynchrony predicts benefit of cardiac resynchronization therapy in patients with end-stage heart failure before pacemaker implantation.

We evaluated patients with end-stage heart failure who have a high likelihood of response to cardiac resynchronization therapy (biventricular pacing). It appears that 20% of patients do not respond to this expensive therapy despite the use of selection criteria (dilated cardiomyopathy, heart failure, New York Heart Association class II or IV, left ventricular ejection fraction <35%, left bundle branch block, and QRS >120 ms). The presence of left ventricular dyssynchrony is needed to result in improvement after cardiac resynchronization therapy.

Aged↗
PubMed2003

Characterizing vulnerable plaque features with intravascular elastography.

BACKGROUND: In vivo detection of vulnerable plaques is presently limited by a lack of diagnostic tools. Intravascular ultrasound elastography is a new technique based on intravascular ultrasound and has the potential to differentiate between different plaques phenotypes. However, the predictive value of intravascular elastography to detect vulnerable plaques had not been studied. METHODS AND RESULTS: Postmortem coronary arteries were investigated with intravascular elastography and subsequently processed for histology. In histology, a vulnerable plaque was defined as a plaque consisting of a thin cap (<250 microm) with moderate to heavy macrophage infiltration and at least 40% of atheroma. In elastography, a vulnerable plaque was defined as a plaque with a high strain region at the surface with adjacent low strain regions. In 24 diseased coronary arteries, we studied 54 cross sections. In histology, 26 vulnerable plaques and 28 nonvulnerable plaques were found. Receiver operator characteristic analysis revealed a maximum predictive power for a strain value threshold of 1.26%. The area under the receiver operator characteristic curve was 0.85. The sensitivity was 88%, and the specificity was 89% to detect vulnerable plaques. Linear regression showed high correlation between the strain in caps and the amount of macrophages (P<0.006) and an inverse relation between the amount of smooth muscle cells and strain (P<0.0001). Plaques, which are declared vulnerable in elastography, have a thinner cap than nonvulnerable plaques (P<0.0001). CONCLUSIONS: Intravascular elastography has a high sensitivity and specificity to detect vulnerable plaques in vitro.

Collagen↗
PubMed2003

Optimizing long-term cardiac management after major vascular surgery: Role of beta-blocker therapy, clinical characteristics, and dobutamine stress echocardiography to optimize long-term cardiac management after major vascular surgery.

BACKGROUND: Survivors of major vascular surgery are at increased risk of late cardiac complications. OBJECTIVE: To examine the cardioprotective effect of beta-blockers. METHODS: A follow-up study was conducted in 1286 patients who survived surgery for at least 30 days. Patients were screened for cardiac risk factors and dobutamine stress echocardiography (DSE) results; 1034 patients (80%) underwent preoperative DSE, and 370 (29%) received beta-blockers. The main outcome measure was late cardiac death or myocardial infarction. RESULTS: Seventy-four patients (5.8%) had late cardiac events. Cardiac event rates in patients with 0, 1 to 2, and 3 or more risk factors were 1.6%, 4.7%, and 19.2%, respectively. In patients without risk factors, beta-blockers were associated with improved event-free survival (2.8% vs 0%), and DSE had no additional prognostic value. In patients with 1 to 2 risk factors, the presence of ischemia during DSE increased cardiac events from 3.9% to 9.8%. However, if patients with ischemia were treated with beta-blockers, the risk decreased to 7.2%. In patients with 3 or more risk factors, DSE and beta-blockers stratified patients into intermediate- and high-risk groups. In patients without ischemia, beta-blockers reduced the cardiac event rate from 15.1% to 9.5%, whereas the cardioprotective effect was limited in patients with 3 or more risk factors and positive DSE findings. CONCLUSIONS: Long-term beta-blocker use is associated with a reduction in the cardiac event rate, except for patients with 3 or more risk factors and positive findings on DSE.

Adrenergic beta-Antagonists↗
PubMed2003

Impact of viability, ischemia, scar tissue, and revascularization on outcome after aborted sudden death.

BACKGROUND: Survivors of aborted sudden death attributable to ventricular arrhythmias in the presence of coronary artery disease are at risk for recurrences. The substrate underlying these arrhythmias is not clear, and therefore the relation between ischemia, viability, scar tissue (and revascularization), and the incidence of ventricular arrhythmias (and survival) was studied over up to 3 years. METHODS AND RESULTS: One hundred fifty-three survivors of sudden death underwent stress-rest perfusion imaging. Patients with ischemic/viable myocardium (n=73) were revascularized if possible. Final antiarrhythmic therapy was based on the outcome of electrophysiological testing or left ventricular ejection fraction (LVEF). Implantation of a defibrillator was performed in 112 (72%) patients. During 3-year follow-up, 15 cardiac deaths occurred and 42 (29%) patients had recurrent ventricular arrhythmias. Patients with events (death or recurrence) exhibited more often a severely depressed LVEF (< or =30%), more extensive scar tissue, and less ischemic/viable myocardium on perfusion imaging and less frequently underwent revascularization. Multivariate analysis identified extensive scar tissue and LVEF < or =30% as the only predictors of death/recurrent ventricular arrhythmias. CONCLUSIONS: In patients with aborted sudden death, extensive scar tissue and severely depressed LVEF are the only predictors of death or recurrent ventricular arrhythmias. These patients should be considered for implantation of a defibrillator.

Aged↗
PubMed2003

Early versus delayed revascularization in patients with ischemic cardiomyopathy and substantial viability: impact on outcome.

BACKGROUND: Patients with ischemic cardiomyopathy and viable myocardium may improve in function and prognosis following revascularization. Delayed revascularization may result in less favorable outcome, and therefore the impact of timing of revascularization on long-term outcome was evaluated. METHODS AND RESULTS: Patients (n=85) with ischemic cardiomyopathy and substantial viability (>or=25% of the left ventricle) on dobutamine stress echocardiography underwent surgical revascularization. Based on the waiting time for revascularization, patients were divided into 2 groups: early ( 1 month) revascularization. Left ventricular ejection fraction (LVEF) was assessed before and 9 to 12 months after revascularization; follow-up data were acquired up to 2 years after revascularization. Hence, 40 patients underwent early (20+/-12 days) and 45 late (85+/-47 days) revascularization. Baseline characteristics of the two groups were comparable. Preoperative deaths were 0 in the early and 2 in the late group. Patients with early revascularization remained shorter time in the intensive care unit (2.4+/-1.5 days versus 5.9+/-2.1 days for the late group, P<0.05). Low output syndrome was observed more frequently in the late group (8% versus 22%, P=0.06). On long-term follow-up, mortality (5% versus 20%, P<0.05) and re-hospitalization for heart failure (10% versus 24%, NS) were higher in the late group. LVEF improved from 28+/-9% to 40+/-12% (P<0.05) in the early group and remained unchanged in the late group (27+/-10% versus 25+/-7%, NS). CONCLUSIONS: Patients with ischemic cardiomyopathy and viable myocardium benefit from early revascularization (with improvement in LVEF and favorable prognosis), whereas delayed revascularization of these patients is associated with worse outcome.

Cardiac Output, Low↗
PubMed2003

Effect of atorvastatin on myocardial contractile reserve assessed by tissue Doppler imaging in moderately hypercholesterolemic patients without heart disease.

An improvement in myocardial longitudinal systolic velocities, assessed by pulsed-wave tissue Doppler imaging during low-dose dobutamine infusion, was observed at 6-month follow-up after 6 months of treatment with atorvastatin. Our findings indicate a favorable effect of atorvastatin on contractile reserve, possibly through an enhancement of flow-dependent coronary dilatation during stress.

Aged↗
PubMed2003

Preoperative comparison of different noninvasive strategies for predicting improvement in left ventricular function after coronary artery bypass grafting.

Thallium-201 (Tl-201) imaging and dobutamine stress echocardiography (DSE) are the most frequently used tests in the clinical setting for assessing viability. However, Tl-201 has a suboptimal specificity and DSE a suboptimal sensitivity to predict functional improvement after revascularization. F18-fluorodeoxyglucose (FDG) imaging is considered highly accurate, but availability is limited. Sequential imaging of Tl-201 and DSE may improve accuracy for assessing viability and may be comparable to FDG. Forty-seven patients with ischemic cardiomyopathy underwent Tl-201 single-photon emission computed tomography (SPECT) at rest (4-hour delayed imaging), DSE, and FDG SPECT before bypass surgery. Sensitivity, specificity, and accuracy of 2 sequential strategies were compared with those of FDG SPECT. Strategy 1 considered Tl-201 imaging as the first step, followed by DSE in patients with an intermediate likelihood of viability on Tl-201. Strategy 2 considered DSE as the first step, followed by Tl-201 imaging. Left ventricular ejection fraction was assessed before and 6 months after revascularization, and improvement of >/=5% was considered significant. Tl-201 had a high sensitivity (95%, p <0.05 vs DSE) with a low specificity (57%, p <0.05 vs DSE). DSE had a low sensitivity (63%, p <0.05 vs Tl-201) with a high specificity (89%, p <0.05 vs Tl-201). Both strategies 1 and 2 resulted in high sensitivities (89% and 89%, respectively) and high specificities (89% and 86%, respectively), compared with FDG SPECT (sensitivity 89%, specificity 86%). Sequential testing by Tl-201 SPECT and DSE has a comparable accuracy to FDG SPECT to predict improvement in left ventricular ejection fraction after revascularization. In centers without access to FDG, sequential imaging with Tl-201 and DSE offers an accurate alternative for assessing myocardial viability.

Aged↗
PubMed2003

Individual prediction of functional recovery after coronary revascularization in patients with ischemic cardiomyopathy: the scar-to-biphasic model.

Currently, the prediction of improvement of left ventricular (LV) ejection fraction (EF) after revascularization in patients with ischemic cardiomyopathy relies only on viable myocardium extent, whereas both the amount of viable and scar tissue may be important. A model was developed, based on the amount of viable and nonviable myocardium, to predict functional recovery. Viable and scarred myocardium was defined by dobutamine stress echocardiography (DSE) in 108 consecutive patients. LVEF before and 9 to 12 months after revascularization was assessed by radionuclide ventriculography; an improvement of > or =5% was considered significant. In the 1,089 dysfunctional segments (63%), DSE elicited biphasic response in 216 segments (20%), sustained improvement in 205 (19%), worsening in 43 (4%), and no change in 625 (57%). LVEF improved in 39 patients (36%). Only the numbers of biphasic and scar segments were predictors of improvement or no improvement of LVEF (odds ratio 1.5, 95% confidence interval 1.2 to 1.7, p <0.0001 for biphasic segments; odds ratio 0.8, 95% confidence interval 0.7 to 0.9, p <0.0005 for scarred segments). The sustained improvement and worsening pattern were not predictive of improvement or no improvement. A regression function, based on the number of scar and biphasic segments, showed that the likelihood of recovery was 85% in patients with extensive biphasic tissue and no scars and 11% in patients with extensive scars and no biphasic myocardium. Patients with a mixture of scar and biphasic tissue had an intermediate likelihood of improvement (50%). In patients with ischemic cardiomyopathy and a mixture of viable and nonviable tissue, both numbers of viable and nonviable segments should be considered to accurately predict functional recovery after revascularization.

Aged↗
PubMed2003

Statins are associated with a reduced incidence of perioperative mortality in patients undergoing major noncardiac vascular surgery.

BACKGROUND: Patients undergoing major vascular surgery are at increased risk of perioperative mortality due to underlying coronary artery disease. Inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A (statins) may reduce perioperative mortality through the improvement of lipid profile, but also through the stabilization of coronary plaques on the vascular wall. METHODS AND RESULTS: To evaluate the association between statin use and perioperative mortality, we performed a case-controlled study among the 2816 patients who underwent major vascular surgery from 1991 to 2000 at the Erasmus Medical Center. Case subjects were all 160 (5.8%) patients who died during the hospital stay after surgery. From the remaining patients, 2 controls were selected for each case and were stratified according to calendar year and type of surgery. For cases and controls, information was obtained regarding statin use before surgery, the presence of cardiac risk factors, and the use of other cardiovascular medication. A vascular complication during the perioperative phase was the primary cause of death in 104 (65%) case subjects. Statin therapy was significantly less common in cases than in controls (8% versus 25%; P<0.001). The adjusted odds ratio for perioperative mortality among statin users as compared with nonusers was 0.22 (95% confidence interval 0.10 to 0.47). Similar results were obtained in subgroups of patients according to the use of cardiovascular therapy and the presence of cardiac risk factors. CONCLUSIONS: This case-controlled study provides evidence that statin use reduces perioperative mortality in patients undergoing major vascular surgery.

Adolescent↗
PubMed2003

Impact of percutaneous coronary intervention or coronary artery bypass grafting on outcome after nonfatal cardiac arrest outside the hospital.

Survivors of cardiac arrest due to ventricular arrhythmias are at risk for recurrent events. The role of revascularization in secondary prevention for survivors of cardiac arrest has been addressed in various studies with conflicting results. A total of 142 survivors of cardiac arrest with coronary artery disease were evaluated according to a standardized protocol, including 2-dimensional echocardiography, myocardial perfusion scintigraphy, coronary angiography, and electrophysiologic testing. Revascularization of scintigraphically documented ischemic myocardial regions was performed in 44 patients (31%). Final therapy was based on the results of electrophysiologic testing. Four-year survival rates were 100% for revascularized noninducible patients, 84% for revascularized inducible patients, 91% for nonrevascularized noninducible patients, and 72% for nonrevascularized inducible patients. Only 1 patient (<1% of study population) died suddenly. Recurrences were much more frequent in patients without revascularization (38% vs 7%, p <0.001) and the recurrence rate was 0% in the revascularized noninducible patients. Thus, revascularization of ischemically jeopardized myocardium in survivors of cardiac arrest resulted in excellent survival; moreover, in absence of inducible ventricular arrhythmias, the recurrence rate was 0%. Systematic evaluation of survivors of cardiac arrest due to ventricular arrhythmias allows risk stratification and guidance of subsequent antiarrhythmic therapy.

Adult↗