Ventilatory thresholds determined from HRV: comparison of 2 methods in obese adolescents.

The development of personalised training programmes is crucial in the management of obesity. We evaluated the ability of 2 heart rate variability analyses to determine ventilatory thresholds (VT) in obese adolescents. 20 adolescents (mean age 14.3±1.6 years and body mass index z-score 4.2±0.1) performed an incremental test to exhaustion before and after a 9-month multidisciplinary management programme. The first (VT1) and second (VT2) ventilatory thresholds were identified by the reference method (gas exchanges). We recorded RR intervals to estimate VT1 and VT2 from heart rate variability using time-domain analysis and time-varying spectral-domain analysis. The coefficient correlations between thresholds were higher with spectral-domain analysis compared to time-domain analysis: Heart rate at VT1: r=0.91 vs. =0.66 and VT2: r=0.91 vs. =0.66; power at VT1: r=0.91 vs. =0.74 and VT2: r=0.93 vs. =0.78; spectral-domain vs. time-domain analysis respectively). No systematic bias in heart rate at VT1 and VT2 with standard deviations <6 bpm were found, confirming that spectral-domain analysis could replace the reference method for the detection of ventilatory thresholds. Furthermore, this technique is sensitive to rehabilitation and re-training, which underlines its utility in clinical practice. This inexpensive and non-invasive tool is promising for prescribing physical activity programs in obese adolescents.

Gene delivery from a DNA controlled-release stent in porcine coronary arteries.

Expandable intra-arterial stents are widely used for treating coronary disease. We hypothesized that local gene delivery could be achieved with the controlled release of DNA from a polymer coating on an expandable stent. Our paper reports the first successful transfection in vivo using a DNA controlled-release stent. Green fluorescent protein (GFP) plasmid DNA within emulsion-coated stents was efficiently expressed in cell cultures (7.9% +/- 0.7% vs. 0.6% +/- 0.2% control, p < 0.001) of rat aortic smooth muscle cells. In a series of pig stent-angioplasty studies, GFP expression was observed in all coronary arteries (normal, nondiseased) in the DNA-treated group, but not in control arteries. GFP plasmid DNA in the arterial wall was confirmed by PCR, and GFP presence in the pig coronaries was confirmed by immunohistochemistry. Thus, DNA-eluting stents are capable of arterial transfection, and could be useful as delivery systems for candidate vectors for gene therapy of cardiovascular diseases.

Safety of thrombolytic therapy in elderly patients with massive pulmonary embolism: a comparison with nonelderly patients.

OBJECTIVES: The aim of the study was to prospectively estimate the safety of thrombolytic therapy in elderly patients with massive pulmonary embolism in comparison with that in nonelderly patients. BACKGROUND: In massive pulmonary embolism, lysis of thrombi can be achieved faster with thrombolytic therapy than with conventional heparin therapy, but it is administered with great caution in elderly patients because the risk of bleeding is thought to be higher than in nonelderly patients. Yet, thrombolytic therapy might be of value in elderly patients also, in allowing potentially more rapid improvement than is achieved with conventional heparin therapy. METHODS: Eighty-nine patients with massive pulmonary embolism defined as Miller score > or = 17/34 underwent thrombolytic therapy without consideration of age if they had no contraindication for such treatment. Fifty-three patients were < or = 70 years old (mean age +/- SD 54 +/- 15 years; range 18 to 70), and 36 patients were > or = 71 years old (78 +/- 5 years; range 71 to 88). Except for mean age, there were no significant differences between the two treatment groups, particularly in terms of clinical presentation, average Miller score and pulmonary artery pressure regimen. Thrombolytic therapy was administered in the form of streptokinase at a dose of 100,000 IU/h over 12 h, with an initial injection of 250,000 IU over 15 min. Heparin was introduced 12 h after initiation of thrombolytic therapy. Urokinase or tissue-type plasminogen activator was used only in case of contraindication to streptokinase. RESULTS: The frequency of uncomplicated clinical course was the same in both treatment groups. Surgical embolectomy was necessary in three nonelderly patients (5.6%) and one elderly patient (2.7%). Changes in pulmonary pressure regimen and Miller score were identical in both groups. Three patients died during the in-hospital course: two nonelderly patients (3.7%) and one elderly patient (2.7%). Minor bleeding occurred in five nonelderly (9.4%) and five elderly (13.8%) patients (p = 0.74). Major bleeding was observed in three nonelderly (5.6%) and five elderly (13.8%) patients (p = 0.29). Bleeding subsequent to early invasive procedure accounted for six (75%) of eight patients with major bleeding: two nonelderly patients (one of whom died) and four elderly patients. No intracranial hemorrhage was observed. No predisposing factor for bleeding was identified, except the need for early vascular access for pulmonary angiography through the femoral approach or for percutaneous insertion of an intracaval device for partial interruption of the inferior vena cava. CONCLUSIONS: Thrombolytic therapy administered for massive pulmonary embolism in patients free of contraindication yields similar results and carries a similar risk for bleeding complications in elderly compared with nonelderly patients. Limiting early invasive procedures may result in less frequent major bleeding complications.

Impact of intravascular ultrasound guidance in stent deployment on 6-month restenosis rate: a multicenter, randomized study comparing two strategies--with and without intravascular ultrasound guidance. RESIST Study Group. REStenosis after Ivus guided STenting.

OBJECTIVES: We aimed to investigate the impact of intravascular ultrasound (IVUS)-guided stent implantation on the 6-month restenosis rate, which has not yet been fully established in randomized trials. BACKGROUND: The 6-month angiographic restenosis rate was compared in patients with symptomatic ischemic heart disease who were randomly allocated to angioplasty and stent deployment, with versus without IVUS guidance. METHODS: After successful stent implantation, patients were randomized into two groups: Group A had no further dilation, and Group B had additional balloon dilation until achievement of IVUS criterion for stent expansion. The study group consisted of 164 patients, assuming a 50% reduction of the restenosis rate in Group B (15% vs. 30%) (alpha = 10%, beta = 20%). RESULTS: We enrolled 155 patients. Overdilation was carried out in 31 (39%) of 79 Group B patients, with the IVUS criterion being achieved in 63 (80%) of 79. No significant difference was observed in the minimal luminal diameter (MLD), but the stent lumen cross-sectional area (CSA) was significantly larger in Group B (mean +/- SD) (7.16 +/- 2.48 vs. 7.95 +/- 2.21 mm2, p = 0.04). At 6 months, there was no significant difference in the restenosis rate, (28.8% [21 of 73] in Group A vs. 22.5% [16 of 71] in Group B, p = 0.25), but according to the observed difference in the restenosis rate, the power of the study was only 40%. The difference in MLD was also nonsignificant (1.60 +/- 0.65 mm in Group A vs. 1.70 +/- 0.64 mm in Group B, p = 0.20), whereas the lumen CSA was 20% larger in the IVUS-guided group (4.47 +/- 2.59 vs. 5.36 +/- 2.81 mm2, p = 0.03). Lumen CSA was the only predictor of restenosis by multivariate logistic regression analysis. CONCLUSIONS: A nonsignificant 6.3% absolute reduction in the restenosis rate and a nonsignificant difference in MLD were observed in this study. Nonetheless, we still cannot rule out a beneficial effect of IVUS guidance, although this may have gone undetected owing to a lack of statistical power. A significant increase was observed in immediate and 6-month lumen size, as detected by IVUS, indicating that ultrasound guidance in stent deployment may be beneficial.

Comparative efficacy of a two-hour regimen of streptokinase versus alteplase in acute massive pulmonary embolism: immediate clinical and hemodynamic outcome and one-year follow-up.

OBJECTIVES: This study sought to compare the efficacy of 2-h regimens of alteplase and streptokinase in acute massive pulmonary embolism. The primary end point was immediate hemodynamic improvement, and secondary end points included early clinical efficacy and safety, as well as 1-year clinical outcome. BACKGROUND: Several thrombolytic regimens have been compared for the past 10 years in randomized studies, showing that 2-h infusion regimens of alteplase or urokinase lead to faster hemodynamic improvement than former 12- to 24-h administration protocols in acute massive pulmonary embolism. Many trials have focused on immediate hemodynamic and angiographic outcomes, but none has addressed long-term follow-up after thrombolysis. METHODS: Sixty-six patients with acute massive pulmonary embolism (Miller score > 17 and mean pulmonary artery pressure >20 mm Hg) were randomly assigned to receive either a 100-mg 2-h infusion of alteplase (n = 23) or 1.5 million IU of streptokinase over 2 h (n = 43). In both groups, heparin infusion was started at the end of thrombolytic infusion and adapted thereafter. Total pulmonary resistance was monitored over a 12-h period. Pulmonary vascular obstruction was assessed 36 to 48 h after thrombolytic therapy. One-year follow-up information included death, cause of death, recurrent pulmonary embolism, chronic thromboembolic pulmonary hypertension, stroke and bleeding. RESULTS: Both groups had similar baseline angiographic and hemodynamic characteristics of severity, with maintained cardiac output in 64 (97%) of 66 patients. The results (mean +/- SD) demonstrated that despite a faster total pulmonary resistance improvement observed at 1 h in the alteplase group compared with the streptokinase group (33+/-16% vs. 19 16%, p = 0.006), a similar hemodynamic efficacy was obtained at 2 h when both thrombolytic regimens were completed (38+/-18% vs. 31+/-19%). There was no significant difference in either pulmonary vascular obstruction at 36 to 48 h or bleeding complication rates. One-year event-free survival was similar in both groups, as most events were related to concomitant diseases. CONCLUSIONS: These results suggest that a 2-h regimen of streptokinase can be routinely used in patients with massive pulmonary embolism and maintained cardiac output without obviously compromising efficacy or safety.

Myocarditis or "true" infarction by cardiac magnetic resonance in patients with a clinical diagnosis of myocardial infarction without obstructive coronary disease: A meta-analysis of individual patient data.

OBJECTIVE: Myocardial Infarction with Non-Obstructed Coronary Arteries (MINOCA) is common, but the causes are to a large extent unknown. Thus, we aimed to study the prevalence of myocarditis and "true" myocardial infarction determined by cardiac magnetic resonance (CMR) imaging in MINOCA patients, and risk markers for these two conditions in this population. METHODS: A search was made in the PubMed and Cochrane databases using the search terms "Myocardial infarction", "Coronary angiography", "Normal coronary arteries" and "MRI". All relevant abstracts were read and seven of the studies fulfilled the inclusion criteria; studies describing case series of patients fulfilling the diagnosis of acute myocardial infarction with normal or non-obstructive coronary arteries on coronary angiography that were investigated with CMR imaging. Data from five of these studies are presented. RESULTS: A total of 556 patients from 5 different sites were included. Fifty-one percent were men with a mean age of 52 ± 16 years. Thirty-three per cent of the patients had myocarditis (n = 183), whereas 21% of the patients had infarction on CMR (n = 115). Young age and a high CRP were associated with myocarditis whereas male sex, treated hyperlipidemia, high troponin ratio and low CRP were associated with "true" myocardial infarction. CONCLUSION AND RELEVANCE: The results of this meta-analysis of individual data showed that myocarditis and "true" myocardial infarction are common in MINOCA when determined by CMR imaging. This information emphasizes the importance of performing CMR imaging in MINOCA patients and can be used clinically to guide diagnostics and treatment of MINOCA patients.

Efficacy of a synthetic pentasaccharide, a pure factor Xa inhibitor, as an antithrombotic agent--a pilot study in the setting of coronary angioplasty.

AIM OF THE STUDY: To assess the antithrombotic properties of SR90107/ORG31540. a sulfated pentasaccharide, which enhances specifically antithrombin III mediated inactivation of factor-Xa, in a clinical setting known to promote arterial thrombosis, i.e. coronary angioplasty. METHODS AND RESULTS: Percutaneous transluminal coronary angioplasty (PTCA) was carried out with conventional balloons with a single 5 min intravenous infusion of 12 mg pentasaccharide, and 500 mg intravenous aspirin. Heparin was not allowed before, during PTCA, and within 24 h after PTCA. The primary end point was the rate of abrupt vessel closure during and within 24 h after the procedure. The sample size was set at 60 evaluable patients, in order to be able to conclude with a good level of confidence (>95%) that the abrupt vessel closure rate was less than 10%, if less than 3 abrupt vessel closures were observed. Seventy-one patients were included in the study, of whom 10 needed elective stenting, and were not considered as evaluable for efficacy. Two out of the 61 remaining evaluable patients experienced acute vessel closure during the study period [3.28%, 95% confidence interval (0.4%; 11.4%)]. No major bleeding occurred. The drug plasma concentrations reached 1.91+/-0.39 mg/], 10 min after pentasaccharide injection, and decreased on average to 1. 18+/-0.27 mg/l at 2 h, and to 0.36+/-0.11 mg/l at 23 h after administration of pentasaccharide. Activated clotting time (ACT) and activated partial thromboplastin (aPTT) time remained within normal range. Thrombin-antithrombin complex levels fell from 22+/-17.1 to 4.5+/-3.4 microg/ml, prothrombin fragment 1+2 levels decreased from 2.15+/-1.01 to 1.73+/-0.87, and activated factor VII levels decreased from 43.4+/-16.8 mU/ml to 18.9+/-7.3 mU/ml respectively from baseline to 2 h following injection of the tested drug. CONCLUSIONS: Administration of pentasaccharide led to the inhibition of thrombin generation without modification of aPTT and ACT. The rate of abrupt vessel closure was within range of rates reported in historical series. Thus we conclude that the anti-thrombotic activity of pentasaccharide, as shown in this pilot trial in the setting of coronary angioplasty, deserves further investigation.

Intracoronary pressure and flow velocity with sensor-tip guidewires: a new methodologic approach for assessment of coronary hemodynamics before and after coronary interventions.

The use of miniaturized pressure and velocity sensors mounted on angioplasty guidewires allows the simultaneous measurement of coronary blood flow velocity and transstenotic pressure gradient, 2 parameters that, combined, should perfectly characterize stenosis hemodynamics. The aim of this article is assessment of the changes in coronary blood flow velocity observed with a Doppler-tipped angioplasty guidewire in 35 patients undergoing balloon angioplasty. We also report our initial experience in 16 patients with the combined use of sensor-tip pressure and Doppler guidewires, and we discuss the application of new methodologic approaches for the study of the coronary circulation allowed by these techniques, such as the instantaneous assessment of the flow velocity/pressure and pressure gradient/flow velocity relations. Before and after angioplasty, flow velocity measurements were obtained distal to the stenosis, both in baseline conditions and after intracoronary injection of 8-12.5 mg of papaverine. The Doppler guidewire was left in place during the dilation procedure and the Doppler signal was continuously recorded during balloon inflation and after deflation to monitor the development of collateral flow, the restoration of flow after balloon deflation, the phase of postocclusive reactive hyperemia, and, incidently, the development of flow-limiting complications. Merits and pitfalls of several flow velocity parameters (average peak velocity, coronary flow velocity reserve, diastolic/systolic velocity ratio), as well as of parameters derived from the combination of pressure and velocity measurements (transstenotic pressure gradient/flow velocity relation and instantaneous diastolic hyperemic flow velocity/pressure relation) were evaluated in 35 patients with, and 37 without, significant coronary stenoses.(ABSTRACT TRUNCATED AT 250 WORDS)

Maximal blood flow velocity in severe coronary stenoses measured with a Doppler guidewire. Limitations for the application of the continuity equation in the assessment of stenosis severity.

In vitro and animal experiments have shown that the severity of coronary stenoses can be assessed using the continuity equation if the maximal blood flow velocity of the stenotic jet is measured. The large diameter and the low range of velocities measurable without frequency aliasing with the conventional intracoronary Doppler catheters precluded the clinical application of this method for hemodynamically significant coronary stenoses in humans. This article reports the results obtained using a 12 MHz steerable angioplasty guidewire in a consecutive series of 52 patients undergoing percutaneous coronary angioplasty (61 coronary stenoses). The ratio between coronary flow velocity in a reference segment and in the stenosis was used to estimate the percent cross-sectional area stenosis. A Doppler recording suitable for quantitation was obtained in the stenotic segment in only 10 of 61 arteries (16%). The time-averaged peak velocity increased from 15 +/- 5 to 115 +/- 26 cm/sec from the reference normal segment to the stenosis. Volumetric coronary flow calculated from the product of mean flow velocity and cross-sectional area was similar in the stenosis and in the reference segment (33.2 +/- 14.9 vs 33.5 +/- 17.0 mL/min, respectively, difference not significant). The percent cross-sectional area stenosis and minimal luminal cross-sectional area derived from the Doppler velocity measurements using the continuity equation and calculated with quantitative angiography were also similar (Doppler, 86.7 +/- 5.1% and 1.00 +/- 0.48 mm2; quantitative angiography, 85.9 +/- 7.9% and 1.02 +/- 0.50 mm2).(ABSTRACT TRUNCATED AT 250 WORDS)

False lumen patency as a predictor of late outcome in aortic dissection.

Aortic dissection (AD) is a disease with a high-risk of mortality. Late deaths are often related to complications in nonoperated aortic segments. Between 1984 and 1996, we retrospectively analyzed the data of 109 patients with acute AD (81 men and 28 women; average age 61 +/- 14 years). All imaging examinations were reviewed, and a magnetic resonance imaging examination was performed at the time of the study. Aortic diameters were measured on each aortic segment. Predictive factors of mortality were determined by Cox's proportional hazard model, in univariate and multivariate analyses, using BMDP statistical software. Follow-up was an average of 44 +/- 46 months (range 24 to 164). Actuarial survival rates were 52%, 46%, and 37% at 1, 5, and 10 years, respectively, for type A AD versus 76%, 72%, and 46% for type B AD. Predictors of late mortality were age >70 years and postoperative false lumen patency of the thoracic descending aorta (RR 3.4, 95% confidence intervals 1.20 to 9.8). Descending aorta diameter was larger when false lumen was patent (31 vs 44 mm; p = 0.02) in type A AD. Furthermore, patency was less frequent in operated type A AD when surgery had been extended to the aortic arch. Thus, patency of descending aorta false lumen is responsible for progressive aortic dilation. In type A AD, open distal repair makes it possible to check the aortic arch and replace it when necessary, decreases the false lumen patency rate, and improves late survival.

Predictors of clinical outcome following percutaneous intervention for in-stent restenosis.

Percutaneous intervention for the first episode of in-stent restenosis was performed in 177 patients 5.4 +/- 0.3 months after native coronary stent implantation. Medical records were reviewed and patients contacted 13.3 +/- 1.2 months after in-stent intervention to ascertain the subsequent clinical course. The effects of demographic, procedural, and angiographic variables on clinical outcomes were determined. At 2 years, Kaplan-Meier estimated survival was 93 +/- 3% and freedom from death, myocardial infarction, and a third target artery revascularization (TAR) was 67 +/- 4%. The actuarial frequency of a third TAR was 26 +/- 4% at 1 year. Stratification of outcomes according to timing of in-stent intervention revealed an approximate twofold higher frequency of adverse events among patients with early (

Planimetry of aortic valve area using multiplane transoesophageal echocardiography is not a reliable method for assessing severity of aortic stenosis.

OBJECTIVE: To assess the reliability of aortic valve area planimetry by multiplane transoesophageal echocardiography (TOE) in aortic stenosis. DESIGN: Study of the diagnostic value of aortic valve area planimetry using multiplane TOE, compared with catheterisation and the continuity equation, both being considered as criterion standards. SETTING: University hospital. PATIENTS: 49 consecutive patients (29 male, 20 female, aged 44 to 82 years, average 66.6 (SD 8.5)), referred for haemodynamic evaluation of an aortic stenosis, were enrolled in a prospective study. From this sample, 37 patients were eligible for the final analysis. METHODS: Transthoracic and multiplane transoesophageal echocardiograms were performed within 24 hours before catheterisation. At transthoracic echo, aortic valve area was calculated by the continuity equation. At TOE, the image of the aortic valve opening was obtained with a 30-65 degrees rotation of the transducer. Numerical dynamic images were stored on optical discs for off-line analysis and were reviewed by two blinded observers. Catheterisation was performed in all cases and aortic valve area was calculated by the Gorlin formula. RESULTS: Feasibility of the method was 92% (48/52). The agreement between aortic valve area measured at TOE (mean 0.88 (SD 0.35) cm2) and at catheterisation (0.79 (0.24) cm2) was very poor. The same discrepancies were found between TOE and the continuity equation (0.72 (0.26) cm2). TOE planimetry overestimated aortic valve area determined by the two other methods. Predictive positive and negative values of planimetry to detect aortic valve area < 0.75 cm2 were 62% (10/16) and 43% (9/21) respectively. CONCLUSIONS: Planimetry of aortic valve area by TOE is difficult and less accurate than the continuity equation for assessing the severity of aortic stenosis.

Predictors of event-free survival after percutaneous mitral commissurotomy.

OBJECTIVE: To assess the long term functional result after percutaneous mitral commissurotomy and identify the predictors of event-free survival following 10 years of experience. DESIGN: Analysis of clinical, echocardiographic, and haemodynamic variables at baseline and after the procedure by univariate and multivariate analyses (Cox model). SETTING: University hospital. PATIENTS: 532 consecutive patients receiving percutaneous mitral commissurotomy in the same institution. RESULTS: The mean (SD) follow up was 3.8 (4.0) years. Survival at 3, 5, and 7.5 years was 94%, 91%, and 83%, respectively; event-free survival was 84%, 74%, and 52%. Mitral valve anatomy was identified as the strongest independent predictor of event-free survival. Age, cardiothoracic ratio, mean pulmonary artery pressure, and mean echocardiographic mitral gradient after commissurotomy were also found to be independent predictors of long term functional results. Event-free survival was 92%, 84%, and 70% at 3, 5, and 7.5 years in patients with favourable anatomy (echo score = 1), 86%, 73%, and 34% in patients with intermediate anatomy (echo score = 2), and 45%, 25%, and 16% in patients with unfavourable anatomy (echo score = 3). In patients aged < or = 65 years, the event-free survival rate was 80%, 70%, and 45% at 3, 5, and 7.5 years v 52%, 38%, and 17% in patients aged > 65 years. CONCLUSIONS: The anatomical form of the mitral valve and the patient's age were the most powerful predictors of event-free survival. Patients with intermediate or unfavourable anatomy and those aged > 65 years have low 5 and 7.5 year event-free survival rates. This must be taken into account when discussing the indications for percutaneous mitral commissurotomy; immediate mitral valve replacement is a reasonable alternative to balloon mitral commissurotomy in patients with higher risk of functional deterioration after the procedure.

Aortic valve replacement in the elderly: a comparative assay of potential risk factor modification.

From January 1989 to October 1992, 208 consecutive patients underwent isolated aortic valve replacement for calcified aortic stenosis in our department. Since the mean age of this patient population was 70 +/- 9 years, a retrospective clinical study was completed to assess the potential influence of advanced age on the independent predictors of early and late mortality. Hospital mortality was 6.2% (13 patients). Total follow up was 422.5 patient-years with a mean of 26 months. Nineteen patients died during the follow up period, equivalent to 4.5% per patient-year late mortality rate. Survival including hospital death was 88 +/- 2%, 86 +/- 2% and 79 +/- 4% at one, two and three years respectively. Eighteen variables as potential predictors of early and late mortality were studied. Predictors of hospital mortality were determined by logistic regression analysis, and those of late mortality by Cox proportional hazard model. Results were expressed as odds ratio (OR) or relative risk (RR). Age greater than 70 years (OR = 9.8, 95% CI = 1.2 to 80) and emergency surgery (OR = 8, 95% CI = 2.1 to 31) appeared as independent predictors of hospital mortality in multivariate analysis. Age above 75 years (RR = 3, 95% CI = 1.1 to 8.3), preoperative acute pulmonary edema (RR = 2.9, 95% CI = 1.1 to 7.7) and emergency surgery (RR = 4.2, 95% CI = 1.2 to 15) were independently associated with decreased late survival. Advanced functional class (NYHA III-IV) was shown to be an independent predictor of early or late mortality only in univariate analysis.(ABSTRACT TRUNCATED AT 250 WORDS)