Biomedical subjects

Gerald Maurer

Publications and source records attributed to Gerald Maurer.

At least 37 records · Page 2Linked to original sources

PubMed2005

Vascular dysfunction after coarctation repair is related to the age at surgery.

BACKGROUND: Despite repair of aortic coarctation, hypertension is frequent in adults and premature coronary and cerebrovascular disease remain of concern. Persistent impairment of arterial dilation has been suspected to contribute to abnormal blood pressure regulation. We tested the hypothesis that arterial reactivity is more likely to be impaired in patients corrected at older age. METHODS: We studied changes in brachial artery diameter in response to reactive hyperemia (FMD) and to nitroglycerin (NMD) in 36 patients and 25 controls. Depending on their age at surgery, patients were divided in group A (surgery <9 years) and group B (surgery > or =9 years). RESULTS: Cholesterol levels and percentage of smokers were similar in patients and controls, but 16 patients had arterial hypertension compared to none of the controls. Endothelium-dependent vasodilation, FMD, and endothelium-independent vasodilation, NMD, were significantly impaired in patients vs. controls (8.2+/-6.2% vs. 13.0+/-5.1%, p<0.001 and 12.9+/-8.0% vs. 18.8+/-9.2%, p<0.01, respectively), both, in hypertensives (8.3+/-6.0%, p<0.01 and 11.8+/-6.0%, p<0.05) and in normotensives (8.1+/-6.5% p<0.01 and 13.8+/-9.3%, p<0.05). However, FMD and NMD in patients of group A did not significantly differ from that in controls (10.0+/-6.7% n.s. and 15.0+/-7.6% n.s.), whereas they were lowest in patients of group B (5.5+/-4.3%, p<0.0001 and 9.6+/-7.7% p<0.001). CONCLUSIONS: Persistent impairment of FMD and NMD after repair of coarctation is more likely to be present in patients corrected at older age. It may be an important contributor to abnormal blood pressure regulation and late morbidity and mortality.

Adolescent↗

PubMed2005

An increase of C-reactive protein is associated with enhanced activation of endogenous fibrinolysis at baseline but an impaired endothelial fibrinolytic response after venous occlusion.

OBJECTIVES: The goal of this study was to determine whether chronic inflammation of the vascular wall may be associated with an impaired activation of the fibrinolytic system. BACKGROUND: Inflammation plays an important role in the initiation and progression of atherosclerosis, and the fibrinolytic system may prevent local thrombus formation. METHODS: We included 50 patients six months after their first myocardial infarction. Plasma levels of the inflammatory marker C-reactive protein (CRP) were determined at basal conditions, and the fibrinolytic parameters tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1) were measured at basal conditions and after a standardized venous occlusion (VO) of the forearm. RESULTS: Patients with high CRP levels (> or =3 mg/l) showed a significantly higher t-PA activity at baseline compared with patients with medium (1 to 2.9 mg/l) and low (<1 mg/l) CRP levels (p <0.005). In contrast, patients with low CRP levels showed a higher increase of t-PA activity (p <0.05) and a higher reduction of PAI-1 activity during VO (p <0.05) compared with patients with medium and high CRP levels. A multivariate analysis that included cardiovascular risk factors and medical treatment showed that CRP is an independent predictor of the t-PA response after a standardized VO. CONCLUSIONS: Chronic low-grade inflammation is associated with enhanced activation of endogenous fibrinolysis at baseline but a reduced fibrinolytic response to VO. This impaired endogenous fibrinolytic capacity might be an important contributor to the increased coronary event rate associated with elevated CRP levels.

Aged↗

PubMed2005

Doppler echocardiographic assessment of valvular regurgitation severity by measurement of the vena contracta: an in vitro validation study.

BACKGROUND: Noninvasive quantitation of valvular regurgitation remains a difficult problem. Measurements of the vena contracta (VC) by color Doppler echocardiography have been proposed but limited data are available on the actual accuracy of this method. METHODS: To evaluate how closely the color Doppler VC reflects the true fluid dynamic VC and the anatomic regurgitant orifice and whether this measurement is affected by flow changes, various models of valvular regurgitation were studied in an in vitro flow circuit. The VC diameter was measured with color Doppler using two different ultrasound systems (Agilent Sonos 5500; Agilent Technologies Inc, Palo Alto, Calif and Vingmed CFM 800; GE Healthcare, Chalfront St Giles, UK). Optical planimetry of the anatomic regurgitant orifice was performed, the true VC diameter was determined by laser particle flow visualization. RESULTS: Because of flow contraction, the true VC diameter was consistently smaller than the anatomic regurgitant orifice diameter. Anatomic orifice and true VC only marginally changed with flow rate. The diameter of the color Doppler VC, however, not only overestimated the anatomic orifice diameter by 45% to 60% and the true VC diameter by 130% to 160%, but was also highly affected by the flow rate and the ultrasound system. Despite these limitations a color Doppler VC diameter of 0.77 cm or more (Agilent) and 0.89 cm or more (Vingmed) detected severe regurgitation with a sensitivity of 93% and 84% and a specificity of 96% and 79%, respectively. CONCLUSIONS: Color Doppler estimates of the VC markedly overestimate regurgitant orifice and true VC. In contrast to the true VC, Doppler measurements are significantly affected by flow rate and by the ultrasound system used. Nevertheless, they allow semiquantitative assessment of valvular regurgitation separating severe from nonsevere regurgitation with acceptable accuracy.

Aortic Valve Insufficiency↗

PubMed2005

Hand-held miniaturized cardiac ultrasound instruments for rapid and effective bedside diagnosis and patient screening.

RATIONALE, AIMS AND OBJECTIVES: Technological progress in recent years has made it possible that ultrasound industry can now offer affordable, portable and battery-operated ultrasound systems the size of a laptop computer. The purpose of this study was to compare these hand-carried ultrasound instruments with standard echocardiography in order to investigate the facility of a rapid bedside diagnosis in patients with suspected or known cardiovascular disease. METHODS: Fifty consecutive patients were studied with miniaturized ultrasound equipment (SonoHeart) and a conventional scanner (Acuson Sequoia) in a blinded manner. All studies were performed by three board-certified cardiologists skilled and experienced in echocardiographic practice. Investigators were not aware of any previous medical reports. RESULTS: With the new system, adequate images could be obtained in all patients. Left ventricular and left atrial diameters measured with the hand-held system correlated well with those obtained with conventional scanning: r = 0.87, mean difference 3.12 +/- 2.7 mm and r = 0.84, mean difference 2.8 + 2.4 mm, respectively. The presence of left ventricular dysfunction, regional wall motion abnormalities, relevant valvular regurgitation (moderate or more) or valve stenosis was correctly diagnosed in all patients. However, there was a tendency towards underestimating the extent of wall motion abnormalities particularly in patients difficult to image. Discrepancies also frequently occurred in patients with trivial or mild regurgitation, where false-positive and false-negative findings were described. CONCLUSION: Currently available hand-held echocardiography systems can facilitate rapid bedside diagnosis and patient screening. However, this recent development in echocardiography also raises a number of questions and its actual impact on general clinical practice still remains to be evaluated.

Cardiovascular Diseases↗

PubMed2005

The adaptive immune system and long-term outcome in patients with stable coronary disease. Predictive value of routine laboratory measurements.

Components of the adaptive immune system, in particular lymphocytes and immunoglobulin, play a major role in advanced atherosclerotic lesions. We sought to determine whether routine, measurements of the relative number of circulating lymphocytes (%L) and gamma-globulin (%G) reflecting immunoglobulin are related to event-free survival in patients with stable coronary artery disease (CAD). We prospectively studied the combined endpoint all-cause mortality, myocardial infarction and coronary revascularization procedures in 141 patients after successful percutaneous coronary intervention during a median follow-up time of 13.2 years. Using Cox regression, we found a significant influence of %L on event-free survival (P=0.007) with a relative risk of 2.21 comparing third to first tertile. Subjects with higher %G values likewise had a shorter event-free survival (P=0.008) with a relative risk of 1.67 comparing third to first tertile. The predictive value of %L and %G remained significant after adjustment for demographic data, cardiovascular risk factors, extent of CAD and other inflammatory markers. We conclude that the fraction of gamma-globulin and in particular the relative lymphocyte cell count may serve as readily available and reliable prognostic tools for the long-term outcome in patients with stable CAD.

Arteriosclerosis↗

PubMed2005

Medical conditions increasing the risk of chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by organized thromboemboli that obstruct the pulmonary vascular bed. Although CTEPH is a serious complication of acute symptomatic pulmonary embolism in 4% of cases, signs, symptoms and classical risk factors for venous thromboembolism are lacking. The aim of the present study was to identify medical conditions conferring an increased risk of CTEPH. We performed a case-control-study comparing 109 consecutive CTEPH patients to 187 patients with acute pulmonary embolism that was confirmed by a high probability lung scan. Splenectomy (odds ratio=13, 95% CI 2.7-127), ventriculo-atrial (VA-) shunt for the treatment of hydrocephalus (odds ratio=13, 95% CI 2.5-129) and chronic inflammatory disorders, such as osteomyelitis and inflammatory bowel disease (IBD, odds ratio=67, 95% CI 7.9-8832) were associated with an increased risk of CTEPH.

Adult↗

PubMed2005

Opposite effects of CX3CR1 receptor polymorphisms V249I and T280M on the development of acute coronary syndrome. A possible implication of fractalkine in inflammatory activation.

Several lines of evidence suggest that the chemokine fractalkine (FKN) and its receptor CX3CR1 contribute to the accumulation of leukocytes in the atherosclerotic plaque. The M280 allele of the CX3CR1T280M polymorphism modulates leukocyte recruitment and is associated with lower prevalence of cardiovascular disease. The influence of V249I, another CX3CR1 polymorphism, is discussed controversially. We investigated the association of the alleles M280 and I249 of CX3CR1 with coronary artery disease (CAD) and with acute coronary syndrome (ACS). Additionally, we assessed their association with the soluble ligand FKN and inflammatory activation measured by high sensitivity C-reactive protein (hsCRP). The genotypes of the V249I and T280M polymorphisms were determined in 1152 patients with suspected CAD.720 (62.5%) individuals showed significant CAD with an ACS prevalence of 59.3%. Using multivariate regression, we found a harmful influence of I249 (adjusted OR=1.8, P<0.03) and a protective effect of M280 (adjusted OR=0.6, P<0.04) on the occurrence of ACS in patients with CAD. Correspondingly, patients with I249 but without M280 (17%) were at elevated risk of ACS (OR=1.6, P<0.04). During ACS these patients (carrying only I249) had significantly higher circulating concentrations of FKN and high sensitivity C-reactive protein (1.9- and 1.6-fold). We found no association of the I249 or the M280 allele with the occurrence of CAD. In conclusion, I249 and M280 have opposite effects on the occurrence of ACS. The presence of I249 not "balanced" by M280 confers an elevated risk of ACS. A FKN-mediated enhanced inflammatory activation might explain this increased risk.

Acute Disease↗

PubMed2005

Ultrasound thrombolysis.

Cardiovascular diseases are a major cause of mortality in the developed world. Efficacy of thrombolysis plays an important role in the management of acute myocardial infarction and cerebral insult both in the acute event and in the long-term outcome of these patients. New adjunctive strategies have been tested, therefore, to make thrombolytic therapies more effective and safer. Ultrasound Thrombolysis is a technique which showed promising results under in vitro conditions and in animal studies. Now clinical trials have to prove if it is also feasible for clinical application. This report gives an overview on different technical approaches and their current performances in the clinical setting. All original articles are chronologically ordered in tables providing detailed information on each study concerning experimental design, acoustical parameters and thrombolysis outcome.

Acoustics↗

PubMed2005

Endurance training reduces circulating asymmetric dimethylarginine and myeloperoxidase levels in persons at risk of coronary events.

Asymmetric dimethylarginine (ADMA), myeloperoxidase (MPO) and paraoxonase 1 (PON1) are directly involved in the pathogenesis of atherosclerosis by modulation of oxidative stress and/or NO bioavailability. We aimed to assess whether endurance exercise which is known to be cardioprotective could beneficially affect these novel risk markers. Thirty-two subjects (31-68 yrs, 56% males) with elevated cardiovascular risk including ten patients with coronary artery disease volunteered for a supervised 12-week endurance training (196 +/- 15 min/week). Their fitness evaluated by 2 km test runs improved significantly after training (pre: 17.3 +/- 0.8 vs. post: 15.7 +/- 0.9 min, p < 0.001). ADMA (pre: 0.94 +/- 0.03 vs. post: 0.75 +/- 0.04 micromol l(-1)) and MPO (pre: 296.8 +/- 22.2 vs.post: 185.7 +/- 19.5 ng ml(-1)) serum levels decreased significantly by 17.6 +/- 4.6% and 28.5 +/- 7.5%, respectively, after training (both p < 0.001). Their down-regulation was inversely correlated (ADMA: r = -0.609, p < 0.001, MPO: r = -0.437, p = 0.014) with the up-regulation of plasma cGMP levels (Cyclic-guanosine 3',5'-monophosphate; pre: 1.6 +/- 0.12 vs. post: 2.21 +/- 0.2 micromol ml(-1), p = 0.001) reflecting NO production. PON1 activity towards phenylacetate was not significantly influenced by training (pre: 133 +/- 6 vs. post: 130 +/- 5 micromol ml(-1) min(-1), p = 0.375). In a matched inactive control group (n = 16) ADMA, MPO, cGMP levels and PON1 activity did not change over time. ADMA, MPO and cGMP changes were significantly different between participants and controls (all p < 0.05). Regular endurance exercise was successful in reducing the circulating levels of two promising cardiovascular risk markers, ADMA and MPO, in persons prone to cardiac events. These changes may result in numerous antiatherosclerotic effects such as improvement of NO bioavailability, reduction of oxidative stress and lipid peroxidation.

Adult↗

PubMed2005

Fractalkine receptor polymorphisms V2491 and T280M as genetic risk factors for restenosis.

The chemokine fractalkine (FKN) recruits leukocytes into lesions of the arterial wall, which may lead to restenosis after stenting. FKN also regulates proliferation of smooth muscle cells, another mechanism pivotal to neointimal thickening. We assessed the hypothesis that functionally important polymorphisms of the FKN receptor CX3CR1 influence restenosis after coronary stenting. Three hundred and sixty-five patients undergoing coronary stenting were genotyped for the CX3CR1 polymorphisms V2491 and T280M. Restenosis occurred in 25% of patients, and recurrent (> 1) restenosis at the target lesion in 8%. The allele 1249 was associated with an increased risk of restenosis (adjusted odds ratio 2.4, 95% confidence interval: 1.3-4.2, P = 0.003) and recurrent restenosis (odds ratio 2.7, 95% confidence interval: 1.3-5.9, P = 0.011). Particularly, patients with 1249 lacking the allele M280 were at an elevated risk of restenosis (P = 0.006) and, accordingly, the haplotype containing 1249 but not M280 was more frequent in patients with restenosis (P = 0.001). In conclusion, the CX3CR1 1249 allele is associated with an increased risk of restenosis while the CX3CR1 M280 allele might counteract the harmful influence of 1249. These findings show the importance of the chemokine FKN and genetic variations of its receptor for restenosis after coronary stenting. Recognition of these inherited risk modifiers may help to individualize treatment of coronary stenosis.

Alleles↗

PubMed2004

Can a commercial diagnostic ultrasound device accelerate thrombolysis? An in vitro skull model.

BACKGROUND AND PURPOSE: Recently, 3 clinical trials revealed encouraging results in recanalization and clinical outcome in acute stroke patients when 2-MHz transcranial Doppler monitoring was applied. This study investigated whether a 1.8-MHz commercial diagnostic ultrasound device has the potential to facilitate thrombolysis using an in vitro stroke model. METHODS: Duplex-Doppler, continuous wave-Doppler, and pulsed wave (PW)-Doppler were compared on their impact on recombinant tissue plasminogen activator (rtPA)-mediated thrombolysis. Blood clots were transtemporally sonicated in a human stroke model. Furthermore, ultrasound attenuation of 5 temporal bones of different thickness was determined. RESULTS: In comparison, only PW-Doppler accelerated rtPA-mediated thrombolysis significantly. Without temporal bone, PW-Doppler plus rtPA showed a significant enhancement in relative clot weight loss of 23.7% when compared with clots treated with rtPA only (33.9+/-5.5% versus 27.4+/-5.2%; P<0.0005). Ultrasound attenuation measurements revealed decreases of the output intensity of 86.8% (8.8 dB) up to 99.2% (21.2 dB), depending on temporal bone thickness (1.91 to 5.01 mm). CONCLUSIONS: Without temporal bone, PW-Doppler significantly enhanced thrombolysis. However, because of a high attenuation of ultrasound by temporal bone, no thrombolytic effect was observed in our in vitro model, although Doppler imaging through the same temporal bone was still possible.

Blood Coagulation↗

PubMed2004

Statins but not angiotensin-converting enzyme inhibitors delay progression of aortic stenosis.

BACKGROUND: Recently, statins and angiotensin-converting enzyme inhibitors (ACEIs) have been shown to slow aortic valve calcium accumulation. Although several studies also suggest that statins may reduce the hemodynamic progression of aortic stenosis (AS), no data are available for ACEIs or the combination of both. METHODS AND RESULTS: A total of 211 consecutive patients (aged 70+/-10 years, 104 females) with native AS, defined by a peak velocity >2.5 m/s (valve area 0.84+/-0.23 cm(2), mean gradient 42+/-19 mm Hg), with normal left ventricular function and no other significant valvular lesion who were examined between 2000 and 2002 and who had 2 echocardiograms separated by at least 6 months were included. Of these, 102 patients were treated with ACEIs, 50 patients received statins, and 32 patients received both. Hemodynamic progression of AS was assessed and related to medical treatment. Annualized increase in peak aortic jet velocity for the entire study group was 0.32+/-0.44 m x s(-1) x y(-1). Progression was significantly lower in patients treated with statins (0.10+/-0.41 m x s(-1) x y(-1)) than in those who were not (0.39+/-0.42 m x s(-1) x y(-1); P<0.0001). This effect was observed both in mild-to-moderate and severe AS. ACEI use, however, did not significantly affect hemodynamic progression (P=0.29). Furthermore, ACEIs had no additional effect on AS progression when given in combination with statins (0.11+/-0.42 versus 0.08+/-0.43 m x s(-1) x y(-1) for combination versus statin only; P=0.81). Cholesterol levels did not correlate with hemodynamic progression either in the group receiving statins or in the group that did not. CONCLUSIONS: ACEIs do not appear to slow AS progression. However, statins significantly reduce the hemodynamic progression of both mild-to-moderate and severe AS, an effect that may not be related to cholesterol lowering.

Aged↗

PubMed2004

Natriuretic peptides predict symptom-free survival and postoperative outcome in severe aortic stenosis.

BACKGROUND: The prognostic value of natriuretic peptides in aortic stenosis (AS) remains unknown. METHODS AND RESULTS: B-type natriuretic peptide (BNP), N-terminal BNP (NtBNP), and N-terminal atrial natriuretic peptide (NtANP) were determined in 130 patients with severe AS (mean age, 70+/-12 years; mean gradient, 64+/-21 mm Hg; valve area, 0.64+/-0.15 cm2) who were followed up for 377+/-150 days. Natriuretic peptides increased with NYHA class and with decreasing ejection fraction (EF). Even asymptomatic patients frequently had elevated neurohormones. Asymptomatic patients who developed symptoms during follow-up had higher BNP and NtBNP levels at entry compared with those remaining asymptomatic (median for NtBNP, 131 pmol/L [interquartile range, 50 to 202 pmol/L] versus 31 pmol/L [range, 19 to 56 pmol/L]; P<0.001). Symptom-free survival at 3, 6, 9, and 12 months for patients with NtBNP <80 versus > or =80 pmol/L was 100%, 88+/-7%, 88+/-7%, and 69+/-13% compared with 92+/-8%, 58+/-14%, 35+/-15%, and 18+/-15%, respectively (P<0.001). Seventy-nine patients eventually underwent surgery because of symptoms. Considering preoperative neurohormone levels, age, NYHA class, aortic valve area, EF, and presence of coronary artery disease, we found that neurohormones, EF, and NYHA class predicted survival; neurohormones predicted postoperative symptomatic status; and neurohormones and preoperative EF predicted postoperative EF. However, by multivariate analysis, NtBNP was the only independent predictor of outcome. CONCLUSIONS: In severe AS, natriuretic peptides provide important prognostic information beyond clinical and echocardiographic evaluation. NtBNP independently predicts symptom-free survival, and preoperative NtBNP independently predicts postoperative outcome with regard to survival, symptomatic status, and left ventricular function. Thus, neurohormones may gain particular importance for timing of surgery in asymptomatic severe AS.

Aged↗

PubMed2004

Adventitial response to intravascular brachytherapy in a rabbit model of restenosis.

BACKGROUND: The incidence of late major adverse cardiac events (MACE) after coronary brachytherapy is higher than in controls. Because expansive remodeling has been shown to correlate with poor clinical outcome after vascular interventions, we studied adventitial changes after intravascular irradiation in a rabbit model. METHODS: Twenty normolipidemic rabbits underwent balloon injury in both external iliac arteries. One artery was assigned for subsequent irradiation with a 90Y source (15 Gy or 30 Gy at 0.5 mm in the vessel wall). After four weeks morphometric measurements were made and cell density and collagen amount determined. Staining for Ki67 identified proliferating cells; apoptotic cells were identified by TUNEL staining. Proliferative and apoptotic indices were calculated as the number of respective positive cells/total cell count x100. RESULTS: The neointimal area decreased to 0.27 +/- 0.3 mm2 after irradiation compared with 0.55 +/- 0.2 mm2 in controls (p=0.007), whereas adventitial area increased from 0.62 +/- 0.3 mm2 to 0.87 +/- 0.3 mm2 (p=0.02). Irradiation reduced both the proliferative (0.95 +/- 2.6 vs. 3.73 +/- 4.7, p=0.026) and apoptotic (0.006 +/- 0.02 vs. 0.107 +/- 0.2, p=0.03) indices in the neointima, but not in the other arterial-wall layers. Collagen amount and arterial remodeling did not differ between the groups. There was no difference between 15 and 30 Gy in any of the parameters, although adventitial thickening was more pronounced in the high-dose group. CONCLUSIONS: In normolipidemic rabbits, intravascular beta-irradiation after balloon angioplasty is associated with an increase in neoadventitia and a reduction of neointima. It is conceivable that this phenomenon may contribute to the increased incidence of late MACE after vascular brachytherapy.

Angioplasty, Balloon↗

PubMed2004

Catecholamines potentiate LPS-induced expression of MMP-1 and MMP-9 in human monocytes and in the human monocytic cell line U937: possible implications for peri-operative plaque instability.

Plaque destabilization leading to myocardial infarction is observed after surgery even if the intervention is of noncardiovascular nature. Mediators of peri- or postoperative stress responsible for such events could include catecholamines and lipopolysaccharide (LPS). Monocytes may be involved in destabilization of atherosclerotic plaques by production of matrix metalloproteinases (MMP). We examined whether catecholamines could affect the expression of MMPs in human monocytes/macrophages and whether catecholamines could modulate LPS-stimulated expression of particular MMPs in these cells. Epinephrine and norepinephrine up-regulated MMP-1 and potentiated LPS-induced expression of MMP-1 in peripheral blood monocytes and monocyte-derived macrophages. We further characterized this effect employing the monocytic cell line U937 and showed that catecholamines potentiate LPS-induced effects on MMP-1 and MMP-9 antigen and activity. mRNA levels of the respective MMPs also increased. These effects did not result from higher mRNA stability but rather from increased transcription possibly induced by enhanced DNA binding of AP-1 and were mediated by either beta1- or beta 2-receptors. If this mechanism is also effective in vivo, our findings might, at least in part, help to explain the observation that cardiac events are important causes of morbidity and mortality after noncardiac surgery and support the findings that peri-operative beta-blockade has been shown to reduce postoperative mortality from cardiac events.

Adrenergic beta-Antagonists↗

PubMed2004

Mild and moderate aortic stenosis. Natural history and risk stratification by echocardiography.

AIMS: To define the natural history and predictors of outcome in mild and moderate aortic stenosis (AS). METHODS AND RESULTS: One hundred and seventy-six consecutive asymptomatic patients (73 women, age 58+/-19 years) with mild to moderate AS (jet velocity 2.5 to 3.9m/s) were followed for 48+/-19 months. Haemodynamic progression and clinical outcome was analysed. Event-free survival with end-points defined as death (n=34) or aortic valve surgery (n=33), was 95+/-2%, 75+/-3% and 60+/-5% at 1, 3 and 5 years, respectively. Both, cardiac and non-cardiac mortality were significantly increased, resulting in a 1.8 times higher mortality than expected (P<0.005). By multivariate analysis, moderate to severe aortic valve calcification, coronary artery disease (CAD) and peak jet velocity were independent predictors of outcome. Event-free survival for patients with moderate or severe valve calcification was 92+/-4%, 61+/-7% and 42+/-7% at 1, 3 and 5 years versus 100%, 90+/-4% and 82+/-5% for patients with no or mild calcification. Patients with calcified aortic valves, CAD or with an event had a significantly faster haemodynamic progression. Of 129 patients with a follow-up echocardiographic exam, 59 (46%) developed severe stenosis during follow-up. CONCLUSION: Outcome of mild and moderate AS is worse than commonly assumed. Rapid progression and excess mortality have to be considered. Significant valve calcification, CAD and rapid progression of aortic jet velocity indicate poor outcome. Patients with these characteristics may require closer follow-up than generally assumed.

Aged↗

PubMed2004

Value and limitations of aortic valve resistance with particular consideration of low flow-low gradient aortic stenosis: an in vitro study.

BACKGROUND: The calculation of valve resistance (R) rather than aortic valve area (AVA) has been proposed for the assessment of aortic stenosis (AS), based on the claim that it is less flow-dependent. Even more importantly, valve resistance has been reported to distinguish between truly severe and "pseudosevere" AS in patients with low cardiac output. However, the diagnostic value of valve resistance remains controversial. METHODS AND RESULTS: Models of stenotic aortic valves (plates and nozzles) and biological stenotic valves were studied in a pulsatile in vitro circuit using Doppler ultrasound and direct pressure and flow measurements. Anatomic AVAs ranged from 0.5 to 1.25 cm2; cardiac output varied from 1.8 to 9.0 l/min. Effective AVA was calculated with the continuity equation. The orifices of the biological valves were recorded with a video camera for planimetry. In low flow-low gradient AS, truly severe stenosis was defined by an AVA remaining <0.85 cm2 after flow normalisation, whereas AVA increased beyond 0.85 cm2 in pseudosevere AS. In rigid stenoses, valve resistance increased significantly with flow, while in bioprostheses this flow dependence was partially masked by an actual increase of the anatomic orifice area. In low flow-low gradient AS, valve resistance was significantly smaller in pseudosevere AS compared to truly severe AS (129 +/- 28 vs. 176 +/- 33 dyne s cm(-5); p<0.001) at a similar baseline effective AVA. After the exclusion of datasets with mean gradients <15 and >35 mmHg, the difference in valve resistance between truly severe and pseudosevere AS was no longer significant (162 +/- 26 vs. 141 +/- 22 dyne s cm(-5); p=0.08). Nevertheless, valve resistance <120 dyne s cm(-5) was found only in pseudosevere stenoses while valve resistance >180 dyne s cm(-5) marked truly severe stenosis. CONCLUSIONS: Valve resistance is flow-dependent and not superior to calculated AVA for the assessment of AS. In low flow-low gradient AS, valve resistance <120 dyne s cm(-5) identifies pseudosevere AS, whereas valve resistance >180 dyne s cm(-5) implies truly severe AS. However, values between 120 and 180 dyne s cm(-5) are nondiagnostic, requiring repeated AVA calculations after flow normalisation.

Aged↗

PubMed2004

The salvage potential of coronary sinus interventions: meta-analysis and pathophysiologic consequences.

OBJECTIVES: Intermittent coronary sinus occlusion has been described to be effective in salvaging ischemic myocardium. This meta-analysis aims to review the efficacy of intermittent coronary sinus occlusion and intermittent coronary sinus occlusion in combination with retroperfusion of arterial blood as methods of myocardial salvage. METHODS: A Medline search was performed to review the published literature on intermittent coronary sinus occlusion. The study inclusion criterion was a randomized, placebo-controlled trial with area of infarction (expressed as a percentage of the area at risk) as the primary end point. RESULTS: Seven experimental trials comprising 125 test animals were found that analyzed the effects of intermittent coronary sinus occlusion on ischemic damage during coronary occlusion. A further 5 studies comprising 88 animals were designed to evaluate the effect of intermittent coronary sinus occlusion in combination with retroperfusion of arterial blood on the infarct size. A meta-analysis of the 7 studies analyzing the effect of intermittent coronary sinus occlusion revealed a significant reduction in infarct size of 29.3% in the treatment group compared with that in the placebo group (P <.001; 95% confidence interval, -40.9 to -17.7). A meta-analysis of the 5 trials analyzing the effect of intermittent coronary sinus occlusion in combination with retroperfusion revealed a reduction in infarct size of 39.4% in the treatment group compared with that in the placebo group (P <.001; 95% confidence interval, -48.9 to -29.9). Comparison between intermittent coronary sinus occlusion and intermittent coronary sinus occlusion in combination with retroperfusion of arterial blood showed no statistical difference (P =.19). An inverse relationship between achieved coronary sinus pressure increase per minute and infarct size could be found in the intermittent coronary sinus occlusion group (r = -0.92; P <.007), whereas in combination with retroperfusion, there was a negative correlation both between achieved coronary sinus pressure and the amount of the retroperfusate and myocardial salvage (r = -0.97; P <.004). CONCLUSIONS: The use of intermittent coronary sinus occlusion and intermittent coronary sinus occlusion in combination with retroperfusion of arterial blood significantly decreases ischemic damage during coronary occlusions. Intermittent coronary sinus occlusion in combination with retroperfusion exhibits no significant profit in salvaging the ischemic myocardium in comparison with that provided by intermittent coronary sinus occlusion alone.

Angioplasty, Balloon↗