Risk factors for exertional rhabdomyolysis with renal stress.

BACKGROUND: Exercise-induced rhabdomyolysis denotes the exertional damage of myocytes with leakage of sarcoplasmic content into the circulation. The purpose of this study was to determine important risk factors for the development of exertional rhabdomyolysis in a temperate climate and to study the renal effects of myoglobinuria. METHODS: A cluster of eight military recruits was admitted to hospital due to exertional rhabdomyolysis with myoglobinuria. The patients were treated according to current guidelines with isotonic saline and alkalinisation of the urine. The eight patients were compared with a randomly selected control group of 26 healthy fellow recruits. All subjects responded to a standardised questionnaire. RESULTS: There were little differences in baseline characteristics between patients and controls. In the present study, exercise intensity, duration and type were all significant determinants of exertional rhabdomyolysis in univariate models. However, in a multivariate model, high exercise intensity on day -1 was the only significant predictor of rhabdomyolysis (p=0.02). All patients had a stable serum creatinine and cystatin C. There was a significant increase in serum neutrophil gelatinase-associated lipocalin (NGAL) in the patients, suggesting renal stress. CONCLUSIONS: Sustained maximal intensity exercise is a crucial risk factor for rhabdomyolysis with gross pigmenturia. Elevated serum NGAL concentrations indicate the presence of renal stress. It appears to be possible to quantify the risk of rhabdomyolysis by means of a simple questionnaire. In the future, this may be used as a tool to prevent rhabdomyolysis.

Hypertension in aortic stenosis: implications for left ventricular structure and cardiovascular events.

The impact of hypertension on left ventricular structure and outcome during progression of aortic valve stenosis has not been reported from a large prospective study. Data from 1616 patients with asymptomatic aortic stenosis randomized to placebo-controlled treatment with combined simvastatin and ezetimibe in the Simvastatin Ezetimibe in Aortic Stenosis Study were used. The primary study end point included combined cardiovascular death, aortic valve events, and ischemic cardiovascular events. Hypertension was defined as history of hypertension or elevated baseline blood pressure. Left ventricular hypertrophy was defined as left ventricular mass/height(2.7) ≥ 46.7 g/m(2.7) in women and ≥ 49.2 g/m(2.7) in men and concentric geometry as relative wall thickness ≥ 0.43. Baseline peak aortic jet velocity and aortic stenosis progression rate did not differ between hypertensive (n = 1340) and normotensive (n = 276) patients. During 4.3 years of follow-up, the prevalence of concentric left ventricular hypertrophy increased 3 times in both groups. Hypertension predicted 51% higher incidence of abnormal LV geometry at final study visit independent of other confounders (P<0.01). In time-varying Cox regression, hypertension did not predict increased rate of the primary study end point. However, hypertension was associated with a 56% higher rate of ischemic cardiovascular events and a 2-fold increased mortality (both P<0.01), independent of aortic stenosis severity, abnormal left ventricular geometry, in-treatment systolic blood pressure, and randomized study treatment. No impact on aortic valve replacement was found. In conclusion, among patients with initial asymptomatic mild-to-moderate aortic stenosis, hypertension was associated with more abnormal left ventricular structure and increased cardiovascular morbidity and mortality.

Usefulness of contrast echocardiography for predicting the severity of angiographic coronary disease in non-ST-elevation myocardial infarction.

Guidelines recommend coronary angiography in patients with non-ST-elevation myocardial infarction (NSTEMI) within 24 to 72 hours, a requirement that cannot always be met. The aim of this study was to evaluate the potential use of contrast echocardiography in prioritizing these patients by identifying those with NSTEMI and angiographically severe coronary artery disease (CAD). Echocardiography was performed before coronary angiography in 110 patients with NSTEMI (67 ± 12 years old, 31% women). Segmental myocardial perfusion and wall motion was scored using a 17-segment left ventricular model. CAD was assessed by quantitative coronary angiography. In the total study population, median troponin T level was 0.27 µg/L (0.13 to 0.86) and Thrombolysis In Myocardial Infarction risk score 3.1 ± 1.5. By quantitative coronary angiography 15% had normal coronary angiographic findings, whereas 1-, 2-, and 3-vessel disease were present in 35%, 27%, and 23%, respectively. Severe CAD (left main stem stenosis, 3-vessel disease, or multivessel disease including proximal stenosis in left anterior descending artery) was found in 42%. Number of segments with hypoperfusion increased with CAD severity from 4.1 ± 2.0 in patients with normal coronary arteries to 5.9 ± 2.4, 7.8 ± 3.5, and 10.4 ± 2.8 in patients with 1-, 2-, and 3-vessel disease, respectively (p<0.01). In multiple logistic regression analysis risk of severe CAD increased by 39% for every additional hypoperfused segment by echocardiography independent of wall motion abnormalities and Thrombolysis In Myocardial Infarction risk score. In conclusion, contrast echocardiography may be used for prediction of angiographic CAD severity in patients with NSTEMI awaiting coronary angiography.

Impact of hypertension on left ventricular structure in patients with asymptomatic aortic valve stenosis (a SEAS substudy).

OBJECTIVE: Both hypertension and aortic valve stenosis induce left ventricular hypertrophy. However, less is known about the influence of concomitant hypertension on left ventricular structure in patients with aortic valve stenosis. METHODS: Baseline Doppler echocardiography was performed in 1720 patients with asymptomatic aortic valve stenosis (peak transaortic velocity >or=2.5 m/s and

High-intensity interval training may reduce in-stent restenosis following percutaneous coronary intervention with stent implantation A randomized controlled trial evaluating the relationship to endothelial function and inflammation.

BACKGROUND: High-intensity interval training has been shown to be superior to moderate continuous exercise training in improving exercise capacity and endothelial function in patients with coronary artery disease. The objective of this study was to evaluate this training model on in-stent restenosis following percutaneous coronary intervention for stable or unstable angina. METHODS AND RESULTS: We prospectively randomized 40 patients after percutaneous coronary intervention with implantation of a bare metal stent (n = 30) or drug eluting stent (n = 32) to a 6-month supervised high-intensity interval exercise training program (n = 20) or to a control group (n = 20). At six months, restenosis, measured as in-segment late luminal loss of the stented coronary area, was smaller in the training group 0.10 (0.52) mm compared to the control group 0.39 (0.38) mm (P = .01). Reduction of late luminal loss in the training group was consistent with both stent types. Peak oxygen uptake increased in the training and control group by 16.8% and 7.8%, respectively (P < .01). Flow-mediated dilation improved 5.2% (7.6) in the training group and decreased -0.1% (8.1) in the control group (P = .01). Levels of high-sensitivity C-reactive protein decreased by -0.4 (1.1) mg/L in the training group and increased by 0.1 (1.2) mg/L in the control group (P = .03 for trend). CONCLUSIONS: Regular high-intensity interval exercise training was associated with a significant reduction in late luminal loss in the stented coronary segment. This effect was associated with increased aerobic capacity, improved endothelium function, and attenuated inflammation.

Low-flow aortic stenosis in asymptomatic patients: valvular-arterial impedance and systolic function from the SEAS Substudy.

OBJECTIVES: This study sought to assess the impact of valvuloarterial impedance on left ventricular (LV) myocardial systolic function in asymptomatic aortic valve stenosis (AS). BACKGROUND: In atherosclerotic AS, LV global load consists of combined valvular and arterial resistance to LV ejection. Global load significantly impacts LV ejection fraction (EF) in symptomatic AS, but less is known about its effect on LV myocardial function in asymptomatic AS. METHODS: Echocardiograms in 1,591 patients with asymptomatic AS (67 +/- 10 years, 51% hypertensive) at baseline in the SEAS (Simvastatin Ezetimibe in Aortic Stenosis) study evaluating placebo-controlled combined simvastatin and ezetimibe treatment in AS were used to assess LV global load as valvuloarterial impedance and LV myocardial function as stress-corrected midwall shortening. The study population was divided into tertiles of global load. Stress-corrected midwall shortening was considered low if <87% in men and <90% in women. Low-flow AS was defined as stroke volume index <22 ml/m(2.04). RESULTS: Energy loss index decreased (0.85 cm(2)/m(2) vs. 0.77 and 0.75 cm(2)/m(2)) and the prevalence of low stress-corrected midwall shortening increased (10% vs. 26% and 63%) with increasing LV global load (all p < 0.001). The EF was low in only 2% of patients. Patients with low-flow AS had higher LV global load and more often low midwall shortening than those with normal-flow AS (9.66 +/- 2.23 mm Hg/ml.m(2.04) and 77%, vs. 6.38 +/- 2.04 mm Hg/ml.m(2.04) and 30%, respectively, p < 0.001). In logistic regression analysis, LV global load was a main predictor of low stress-corrected midwall shortening independent of male sex, concentric LV geometry, LV hypertrophy (all p < 0.001), concomitant hypertension, and aortic regurgitation. CONCLUSIONS: LV global load impacts LV myocardial function in asymptomatic AS independent of other main covariates of LV systolic function. LV myocardial systolic dysfunction is common in asymptomatic AS in particular in patients with low-flow AS and increased valvuloarterial afterload, whereas EF is generally preserved. (An Investigational Drug on Clinical Outcomes in Patients With Aortic Stenosis [Narrowing of the Major Blood Vessel of the Heart]; NCT00092677).

Quantitative contrast stress echocardiography in assessment of restenosis after percutaneous coronary intervention in stable coronary artery disease.

AIMS: Quantitative contrast stress echocardiography (CSE) can assess regional myocardial perfusion. The aim of this study was to evaluate the performance of quantitative CSE in the detection of restenosis after percutaneous coronary intervention (PCI). METHODS AND RESULTS: Thirty-three patients with stable coronary artery disease, scheduled for PCI, underwent CSE and quantitative coronary angiography (QCA) before and 9 months after PCI. Regional myocardial perfusion was analysed blinded to QCA results. QCA identified 38 significant stenoses (> or =50% diameter reduction). Before PCI, perfusion during stress was significantly reduced in regions supplied by stenotic arteries; blood flow velocity (Deltabeta) -3.9 (-9.0 to 0.5) s(-1), perfusion rate (DeltaA x beta) -175.0 (-518.0 to 58.5) s(-1), and refilling time (Deltart) 210 (-22 to 452)ms, compared with the perfusion increase seen in regions supplied by non-stenotic arteries; Deltabeta 1.6 (-0.7 to 4.4) s(-1), DeltaA x beta 151.7 (-67.0 to 300.5) s(-1), and Deltart -47 (-195 to 89) ms, all P < 0.05. At follow-up, regional stress-induced perfusion improved in 29 regions with successful PCI; Deltabeta 0.1 (-2.7 to 3.6), DeltaA x beta 30.5 (-133.3 to 232.1), and Deltart -99 (-247 to 125), all P < or = 0.01, although there was no improvement in nine regions with restenosis; Deltabeta 0.9 (-1.5 to 5.3), DeltaAxbeta 65.7 (-40.8 to 412.6), and Deltart -79 (-268 to 163), P = NS. CONCLUSION: Quantitative CSE has the potential to detect angiographically significant coronary artery stenoses as well as angiographic success after PCI.

Myocardial contrast echocardiography in assessment of stable coronary artery disease at intermediate dobutamine-induced stress level.

BACKGROUND: Myocardial contrast stress echocardiography (stress MCE) is a novel method for diagnosing coronary artery disease (CAD). Few studies have compared the diagnosis of ischemia by stress MCE to angiographic CAD. METHODS: Dobutamine stress MCE and SonoVue contrast infusion were performed before an elective percutaneous coronary intervention in 37 patients (8 women) aged 45-75 years with symptomatic CAD and at least one significant coronary artery stenosis measured by quantitative coronary angiography (QCA). The total and regional perfusion and wall motion (WM) were scored as normal or abnormal and attributed to the three main epicardial coronary arteries using a 17-segment left ventricular model. RESULTS: An intermediate stress level was obtained in 29 (78%) patients, and 2 (5%) patients obtained peak stress. A perfusion defect was detected in 92% and WM abnormality in 57% of the patients at peak stress (P < 0.01). By perfusion, 70% of stenoses were both detected and correctly anatomically located, compared to 42% by WM (P < 0.01). All 21 patients with multivessel disease and/or proximal left anterior descending (LAD) stenosis measured by QCA were identified by stress-induced perfusion defects, while only 11 of them were identified by WM abnormalities (P < 0.01). CONCLUSION: Perfusion scoring is superior to WM scoring during stress MCE for diagnosing significant CAD in patients obtaining intermediate stress level, in particular, when multivessel disease or proximal LAD stenosis is present.

Factors influencing left ventricular structure and stress-corrected systolic function in men and women with asymptomatic aortic valve stenosis (a SEAS Substudy).

To identify determinants of left ventricular (LV) structure and stress-corrected systolic function in men and women with asymptomatic aortic stenosis (AS), Doppler echocardiography was performed at baseline in 1,046 men and 674 women 28 to 86 years of age (mean 67 +/- 10) recruited in the Simvastatin Ezetimibe in Aortic Stenosis (SEAS) study evaluating placebo-controlled combined simvastatin and ezetimibe treatment in AS. LV hypertrophy was less prevalent in women despite older age, higher systolic blood pressure, and smaller aortic valve area/body surface area (all p values <0.05). In logistic regression analyses, LV hypertrophy was independently associated with male gender, severity of AS, hypertension, higher systolic blood pressure, and lower stress-corrected midwall shortening (scMWS) or stress-corrected fractional shortening (scFS; all p values <0.01). In men aortic regurgitation also was a predictor of LV hypertrophy (p <0.05). Women had greater scFS and scMWS when corrected for LV size or geometry (all p values <0.001). In multivariate analyses, female gender predicted 11% greater scFS and 4% greater scMWS independent of age, body mass index, heart rate, aortic valve area, LV mass, relative wall thickness, aortic regurgitation, hypertension, and end-systolic stress (R(2) = 0.23 and 0.59, respectively, p <0.001). In conclusion, the major determinants of LV hypertrophy in patients with asymptomatic AS are male gender, severity of AS, and concomitant hypertension. Women have higher stress-corrected indexes of systolic function independent of LV geometry or size, wall stress, older age, or more concomitant hypertension.

Blood pressure measurements by the Keito machine. Evaluation versus office blood pressure by physicians.

BACKGROUND: The Keito machine offers automatic measurements of blood pressure (BP), height and weight on insertion of coins and has been introduced in pharmacies. DESIGN: Cross-sectional study comparing automatic BP measurements by the Keito machine to office BP measurements by physicians. METHODS: Patients scheduled for pre-catheterisation screening participated in the study. Their BP was first measured using the Keito machine, then by physicians. Office BP was recorded as the last of three consecutive BP measurements recorded with one-min intervals after a five-min rest in the sitting position. In a sub-study BP was measured simultaneously during the Keito measurement by a physician. RESULTS: In 390 consecutive patients average BP was significantly lower with the Keito machine compared to office BP measurements made by the physicians (136/75+/-19/8 mmHg versus 141/79+/-21/10 mmHg, both p<0.001). The correlation coefficient (r) was 0.56 (p<0.001) for systolic BP (SBP) and 0.53 (p<0.001) for diastolic BP (DBP). Bland-Altman analysis showed a mean difference (+/-2 SD) for SBP and DBP of -5 (+/-37) and -4 (+/-17) mmHg, respectively. When defining hypertension (HT) as office SBP> or =140 and/or DBP> or =90 mmHg, the Keito method diagnosed 83% of the systolic and 62% of the diastolic hypertensive population correctly. The classification of systolic and diastolic normotensive was correct in 61% and 86%, respectively. CONCLUSION: Agreement between office and Keito BP is poor. The Keito machine underestimates SBP on average by 5 mmHg and DBP by 4 mmHg, which may be of significance for diagnosing HT and starting anti-hypertensive therapy. However, the difference can be much larger in individual patients. Therefore, the Keito machine cannot be recommended for medical screening of HT or as a replacement for follow-up by physicians.

Assessment of parallel conductance for the trans-cardiac conductance method: can we use the hypertonic saline method with pulmonary artery injections?

The trans-cardiac conductance (TCC) method provides on-line left ventricular (LV) volume signals by determining the electrical conductance of blood in the LV using central venous and epithoracic electrodes. Conductive structures outside the LV cause a 'parallel conductance' offset term (Vp) that is determined by bolus injections of hypertonic saline in the pulmonary artery (Vp(saline)). Analysis of the increased conductance signal during passage of the bolus through the LV yields Vp(saline). Since TCC signals are picked up by epithoracic electrodes, concern has been raised that hypertonic saline remaining in the lungs might lead to overestimation. The decrease in blood conductivity induced by injection of non-ionic contrast medium during a LV angiogram may also be used to determine Vp (Vp(contrast)). Since the contrast is injected directly into the LV, lung conductance should be unaltered. Thus, we compared Vp(saline) with Vp(contrast) in six anaesthetized sheep during different hemodynamic conditions. Linear regression showed that Vp(saline) = 0.99 Vp(contrast) + 2.45 ml (r2 = 0.99). Bland-Altman analysis yielded a small non-significant bias (+/-2SD) of 1.8 (+/-6.8) ml. We conclude that parallel conductance for TCC can be accurately determined with the conventional hypertonic saline method.

Transcardiac conductance for continuous measurement of left ventricular volume: validation vs. angiography in patients.

OBJECTIVE: To test the feasibility of the transcardiac conductance (TCC) method for continuous, on-line measurement of absolute left ventricular (LV) volume and to validate the method by comparison with biplane angiography. DESIGN AND SETTING: Prospective clinical feasibility and validation study in a cardiac catheterization laboratory in a university hospital. PATIENTS AND INTERVENTIONS: Ten patients scheduled for electrophysiological studies ( n=5), percutaneous transluminal coronary angioplasty ( n=3), and left- and right-sided cardiac catheterization ( n=2) were enrolled in the feasibility study. Twenty patients scheduled for diagnostic left- and right-sided cardiac catheterization were included in the validation study. The latter were studied at baseline and during right atrial pacing 30 beats/min above baseline. MEASUREMENTS AND RESULTS: In the feasibility study satisfactory ventricular volume signals were obtained by TCC in eight of ten patients. In the validation study calibration factors (alpha and V(p)) for TCC were obtained by thermodilution and hypertonic saline dilution, to yield absolute LV volume. Results indicate a good linear correlation with angiographic volume ( R(2)=0.78) with an intercept of 10+/-15 ml, not significantly different from 0 and slope of 1.17+/-0.16. Mean calibration factors alpha and V(p) were 0.017+/-0.002 (interpatient variability 0.018) and 75.1+/-0.4 ml (interpatient variability 35.4 ml), respectively. CONCLUSIONS: The TCC method provides on-line and continuous LV volume signals in patients in a relatively noninvasive way. Calibration yields absolute LV volumes with a good linear correlation in comparison to biplane LV angiography. TCC appears to be a promising methodology for monitoring absolute LV volume in the ICU.

End-diastolic and end-systolic volume from the left ventricular angiogram: how accurate is visual frame selection? Comparison between visual and semi-automated comnputer-assisted analysis.

BACKGROUND: End-diastolic (ED), end-systolic (ES) left ventricular (LV) volumes and LV ejection fraction (LVEF) are important parameters for clinical decision making in heart disease. In clinical practice the frames from cine-angiography with the largest and smallest opacified LV areas are visually selected and the endocardial borders traced as LVED and LVES contours, respectively. We compared the accuracy of this visual method using two frames with a semi-automated computer assisted frame-by-frame analysis of the complete opacified cardiac cycles. METHODS AND RESULTS: In 17 patients a biplane LV cine-angiogram was obtained at 25 frames/s. Complete frame-by-frame analysis was performed using semi-automatic border detection software. Experienced independent observers visually selected and manually traced LVED and LVES in the so-called visually assessed two-frame method in a consensus meeting. LV volumes were calculated by the area-length method. Mean LVEDV, LVESV and LVEF were 133 +/- 57, 56 +/- 40 ml and 61 +/- 16%, respectively, for the visually assessed two-frame method, and 117 +/- 49, 53 +/- 33 ml and 60 +/- 13%, respectively, for the semi-automated computer assisted frame-by-frame method. LVEDV was significantly higher in the visually assessed two-frame method (p < 0.01). Linear regression analysis showed an excellent correlation between semi-automated computer-assisted frame-by-frame and the visually assessed two-frame LVEDV (y = 1.2x - 2.9; r2 = 0.98), LVESV (y = 1.2x - 8.2; r2 = 0.97) and good linear correlation for LVEF (p = 1.2x - 3.6; r2 = 0.82). Bland-Altman analysis showed respectively a bias of 16.4, 2.4 ml and 5.0% with overall wide limits of agreement (-6.6 and 39.4 ml; -16.6 and 21.4 ml; -9.0% and 19.1%). CONCLUSION: Correlation is excellent when visually assessed LVED and LVES are compared with a semi-automated computer assisted frame-by-frame analysis. However, the visually assessed two-frame method tends to overestimate the volumes obtained by semi-automated computer-assisted frame-by-frame analysis, especially for LVEDV, indicating that visual selection will yield a higher LVEF, which may influence clinical decision making.

The trans-cardiac conductance method for on-line measurement of left ventricular volume: assessment of parallel conductance offset volume.

The trans-cardiac conductance (TCC) method provides on-line left ventricular (LV) volume signals by determining the electrical conductance of blood in the LV by means of central venous and epithoracic electrodes. Conductive structures outside the LV blood pool cause a "parallel conductance" offset term (Vp) that can be determined by bolus injections of hypertonic saline in the pulmonary artery (Vp(saline)), which cause a transient increase in blood conductivity. This study in anesthetized sheep evaluates the accuracy of the saline calibration method and the variabilities of Vp between animals, between hemodynamic conditions and during the cardiac cycle. The conventional intra-cardiac conductance catheter method was used to obtain independent estimates of Vp by the zero-volume method (Vp(zero volume)). Mean baseline Vp(saline) and Vp(zerovolume) were 104 +/- 6 ml and 106 +/- 6 ml, respectively. Bland-Altman analysis showed a small nonsignificant bias (-2.5 ml) and narrow limits of agreement (4.6 ml). Vp was not significantly different between hemodynamic conditions (baseline, dobutamine, volume load, propranolol), but had a substantial interanimal variability (IAV) (38%). Average variations during the cardiac cycle were < 10% of mean Vp. We conclude that the saline method can be applied to determine Vp for TCC. IAV is substantial, so that Vp must be determined in each animal, but within-animal variability is relatively small.

Continuous on-line measurement of absolute left ventricular volume by transcardiac conductance: angiographic validation in sheep.

OBJECTIVE: Validation of the transcardiac conductance method for continuous, on-line measurement of absolute left ventricular volume by comparison with biplane angiography. DESIGN: Controlled, prospective animal study. SETTING: Catheterization laboratory of the Leiden University Medical Center. SUBJECTS: Six anesthetized sheep. INTERVENTIONS: Subjects were studied at baseline, during infusion of dobutamine, and during volume loading and beta blockade. In a pilot experiment, a coronary artery was occluded by a balloon, and the behavior of the transcardiac conductance signals during ischemia was tested. MEASUREMENTS AND MAIN RESULTS: Calibration factors alpha and V(p) were determined by thermodilution and hypertonic saline dilution, respectively. Calibrated transcardiac conductance volume was compared with angiographic volume in four different hemodynamic conditions, and transcardiac conductance measurements were registered during a period of ischemia. Results showed a good linear correlation between transcardiac conductance and angiographic volume (r =.77, p <.01) with an intercept of 12.5 +/- 5.6 mL (interanimal variability, 17.8 mL) and a slope of 1.49 +/- 0.15 (interanimal variability, 0.34). Mean alpha and V(p) were 0.12 +/- 0.01 (interanimal variability, 0.07) and 104 +/- 3 mL (interanimal variability, 38 mL), respectively. V(p) did not vary significantly between conditions, and alpha varied only during propranolol (p =.04). Transcardiac conductance enabled immediate visualization of acute left ventricular volume changes during coronary occlusion in a pilot experiment. CONCLUSIONS: Transcardiac conductance is a method to register an on-line, continuous, left ventricular volume signal, which correlates well with angiography. However, calibration factors need to be determined in individual subjects. The method appears promising to monitor absolute volume in the intensive care unit.