Repeated coronary artery occlusions during routine balloon angioplasty do not induce myocardial preconditioning in humans

AbstractObjectives.The purpose of the present study was to assess whether brief, repeated coronary artery occlusions during balloon angioplasty induce a myocardial ischemic protective effect.Background.In animals, brief coronary artery occlusions preceding a more prolonged occlusion result in reduced infarct size. Whether myocardial protection against ischemia could also occur in humans during angioplasty remains controversial.Methods.Thirteen patients with a proximal left anterior descending coronary artery stenosis with no angiographic collateral circulation underwent percutaneous transluminal coronary artery balloon angioplasty. Three 120-s balloon inflations separated by a 5-min equilibrium period were performed. For each inflation, intracoronary ST segment modifications, septal wall thickening (M-mode echocardiography), left ventricular pressures and time derivatives were measured at baseline and at 30, 60 a d 90 s after balloon inflation and 120 s after balloon deflation.Results.Intracoronary electrocardiographic analysis showed that the time course of the maximal ST segment elevation was identical at each inflation, as were wall motion changes assessed by the decrease in septal wall thickening. For the first and last inflations, peak positive dP/dt decreased significantly by 13 ± 9% (mean ± SD) and 14 ± 13%, whereas peak negative dP/dt increased by 23 ± 15% and 22 ± 10%, respectively (all p < 0.01 from baseline values). The relaxation time constant, tau, was altered similarity during the different inflations, from 44 ± 6 to 74 ± 13 ms and from 57 ± 13 to 77 ± 13 ms (all p < 0.001) for the first and last inflations, respectively. Left ventricular endiastolic pressure increased to the same level after each inflation. In contrast to other hemodynamic variables, tau and left ventricular end-diastolic pressure did not return to baseline values in between the inflations, which may be due to myocardial stunning.Conclusions.In patients with proximal left anterior descending coronary artery stenosis and no evidence of collateral circulation, brief periods of ischemia, such as those used during routine coronary balloon angioplasty, do not provide any protection against myocardial ischemia

Development of a human model for the study of effects of hypoxia, exercise, and sildenafil on cardiac and vascular function in chronic heart failure

Background: Pulmonary hypertension is associated with poor outcome in patients with chronic heart failure (CHF) and may be a therapeutic target. Our aims were to develop a noninvasive model for studying pulmonary vasoreactivity in CHF and characterize sildenafil's acute cardiovascular effects. Methods and Results: In a crossover study, 18 patients with CHF participated 4 times [sildenafil (2 × 20 mg)/or placebo (double-blind) while breathing air or 15% oxygen] at rest and during exercise. Oxygen saturation (SaO2) and systemic vascular resistance were recorded. Left and right ventricular (RV) function and transtricuspid systolic pressure gradient (RVTG) were measured echocardiographically. At rest, hypoxia caused SaO2 (P = 0.001) to fall and RVTG to rise (5 ± 4 mm Hg; P = 0.001). Sildenafil reduced SaO2 (−1 ± 2%; P = 0.043), systemic vascular resistance (−87 ± 156 dyn·s−1·cm−2; P = 0.034), and RVTG (−2 ± 5 mm Hg; P = 0.05). Exercise caused cardiac output (2.1 ± 1.8 L/min; P &lt; 0.001) and RVTG (19 ± 11 mm Hg; P &lt; 0.0001) to rise. The reduction in RVTG with sildenafil was not attenuated by hypoxia. The rise in RVTG with exercise was not substantially reduced by sildenafil. Conclusions: Sildenafil reduces SaO2 at rest while breathing air, this was not exacerbated by hypoxia, suggesting increased ventilation–perfusion mismatching due to pulmonary vasodilation in poorly ventilated lung regions. Sildenafil reduces RVTG at rest and prevents increases caused by hypoxia but not by exercise. This study shows the usefulness of this model to evaluate new therapeutics in pulmonary hypertension

316: Diuretic is safe and superior to volume expansion in normotensive patients with acute pulmonary embolism and right ventricular dilatation

BackgroundThe rational and the benefit of load expansion is controversial in acute pulmonary embolism (PE). Diuretic may reduce RV preload and improve hemodynamic status. The present study reported the safety of furosemide in normotensive acute PE with oligo-anuria.Methods and ResultsWe prospectively included 68 consecutive normotensive patients (systolic blood pressure ≥90mmHg) admitted for acute PE with oligoanuria and RV dilation. RV dilation was defined by a right and left ventricular diameter ratio >0.6. Overall, 29 patients were treated by a repeated bolus of furosemide (83±84mg, range 40 to 160mg), while 39 patients received isotonic saline solution (1.6±0.8 L, range, 0.5 to 4,0L). Patients treated by furosemide and fluid expansion had similar severity of hypoxemia but the furosemide group had lower admission blood pressure (119±21mmHg vs. 132±18mmHg, P=0.007) and greater shock index defined as heart rate and blood pressure ratio (0.81±0.23 vs. 0.69±0.18, P=0.02). Despite these differences, only the furosemide group had decrease shock index (0.81±0.23 vs. 0.62±0.17, P<0.0001) with improved systolic blood pressure (119±21mmHg vs. 133 ±18mmHg, P<0.001), heart rate (93±19bpm vs. 81±18bpm, P<0.001), and creatinin level. Finally, more patients were weaned in oxygen at 24 hours (39% vs. 19%) and in-hospital survival without death and PE-related shock was similar between the two groups (93% vs. 95%).ConclusionsIn normotensive PE with oligoanuria and RV dilatation, diuretic can be safely delivered to improve systolic blood pressure and oxygenation

120 Superiority of CT scan over transthoracic echocardiography in predicting aortic regurgitation after TAVI

BackgroundParavalvular aortic regurgitation (AR) occurs in up to 86% of patients undergoing Transcatheter Aortic Valve Implantation (TAVI). Its prevalence remains unchanged after one year follow-up but its determinants are unclear. We sought to evaluate the impact of annulus measurement by transthoracic echocardiography (TTE) and by CT scan on the occurrence of AR.MethodsThe study included 43 symptomatic patients (83±8 years, 72% in NYHA≥III) with severe aortic stenosis [0.76±0.19cm2, mean gradient 42±14mmHg] who underwent TAVI using CoreValve® LLC Percutaneous Aortic Valve Implantation System, Medtronic, Minneapolis USA. Left ventricular outflow tract (LVOT) area was computed from LVOT diameter (21±2mm) by TTE using a spherical model and from CT using an ellipsoidal model according to the larger (25±3mm) and the smaller outflow tract diameters (22±3mm). These data were compared to the prosthesis area and the occurrence of AR after TAVI.ResultsIn patients with AR greater or equal to 2/4 (32%), LVOT area measured by CT was significantly greater as compared to patients with no or mild AR (478±65mm 2 vs. 411±85mm2, p=0.009). Furthermore, the difference between actual prosthesis area and LVOT area measured by CT scan was significantly smaller (113±55 vs. 171±67, p=0.009) in patients with significant AR (≥2/4) after TAVI. In contrast, LVOT area from TTE did not correlate with AR severity.ConclusionCT scan is more accurate than TTE for calculating LVOT area for prosthesis sizing before TAVI in order to avoid post-implantation AR

073 Right Ventricle Contractile Reserve as a Pre-operative Tool for Assessing RV failure after Continuous Flow LVAD Implantation

IntroductionLatest generation continuous flow left ventricular assist devices (LVADs) have been proposed as an alternative to heart transplantation for end-stage heart failure. However, postoperative right ventricle (RV) dysfunction remains common and has a negative impact on prognosis. Purpose of our study was to identify echocardiographic or hemodynamic parameters that could predict early RV failure after LVAD implantation in patients with biventricular dysfunction.MethodsFourteen patients with biventricular dysfunction who have been evaluated for LVAD implantation were included. Right and left ventricular dysfunction were respectively defined as: tricuspid annular plane excursion < 16 mm (TAPSE) and LV ejection fraction < 35%. In all patients, preoperative measurements were obtained at rest. In 7 patients, right heart catheterization was performed simultaneously with increasing doses of dobutamine (15γ/Kg/min). Primary endpoint was death caused by right ventricle systolic dysfunction or need for right ventricle mechanical support within 30 days after surgery (RVSD+).ResultsMean recipient age was 58±7 years. Primary end-point (RVSD+) was noted in five patients. Preoperative demographic, echocardiographic and hemodynamic data were similar between RVSD+ and RVSD- patients (Table). Percent increase of TAPSE and systolic PAP between basal and high dobutamine dose was significantly lower in RVSD+ than in RVSD- patients.ConclusionPercent increase of TAPSE and systolic PAP induced by high dose dobutamine infusion might be two interesting criteria to assess RV contractile reserve and predict RV outcome after LVAD implantation in patient with biventricular dysfunction.Baseline Measurement (n=14)Change after Dobutamine infusion,% (n=7)RVSD-RVSD+pRVSD-RVSD+pN95TAPSE, mm14±214±20.955±526±20.03Systolic PAP, mmHg51±753±60.842±84±70.05Cardiac Output, l/min3.3±0.53.5±0.50.987±1093±470.7Pulm Vasc Res, Wood3.9±14.3±10.62±41-36±70.

Patent Foramen Ovale Closure or Anticoagulation vs. Antiplatelets after Stroke

BACKGROUND Trials of patent foramen ovale (PFO) closure to prevent recurrent stroke have been inconclusive. We investigated whether patients with cryptogenic stroke and echocardiographic features representing risk of stroke would benefit from PFO closure or anticoagulation, as compared with antiplatelet therapy. METHODS In a multicenter, randomized, open-label trial, we assigned, in a 1:1:1 ratio, patients 16 to 60 years of age who had had a recent stroke attributed to PFO, with an associated atrial septal aneurysm or large interatrial shunt, to transcatheter PFO closure plus long-term antiplatelet therapy (PFO closure group), antiplatelet therapy alone (antiplatelet-only group), or oral anticoagulation (anticoagulation group) (randomization group 1). Patients with contraindications to anticoagulants or to PFO closure were randomly assigned to the alternative noncontraindicated treatment or to antiplatelet therapy (randomization groups 2 and 3). The primary outcome was occurrence of stroke. The comparison of PFO closure plus antiplatelet therapy with antiplatelet therapy alone was performed with combined data from randomization groups 1 and 2, and the comparison of oral anticoagulation with antiplatelet therapy alone was performed with combined data from randomization groups 1 and 3. RESULTS A total of 663 patients underwent randomization and were followed for a mean (+/- SD) of 5.3 +/- 2.0 years. In the analysis of randomization groups 1 and 2, no stroke occurred among the 238 patients in the PFO closure group, whereas stroke occurred in 14 of the 235 patients in the antiplatelet-only group (hazard ratio, 0.03; 95% confidence interval, 0 to 0.26; P&lt;0.001). Procedural complications from PFO closure occurred in 14 patients (5.9%). The rate of atrial fibrillation was higher in the PFO closure group than in the antiplatelet-only group (4.6% vs. 0.9%, P = 0.02). The number of serious adverse events did not differ significantly between the treatment groups (P = 0.56). In the analysis of randomization groups 1 and 3, stroke occurred in 3 of 187 patients assigned to oral anticoagulants and in 7 of 174 patients assigned to antiplatelet therapy alone. CONCLUSIONS Among patients who had had a recent cryptogenic stroke attributed to PFO with an associated atrial septal aneurysm or large interatrial shunt, the rate of stroke recurrence was lower among those assigned to PFO closure combined with antiplatelet therapy than among those assigned to antiplatelet therapy alone. PFO closure was associated with an increased risk of atrial fibrillation

Glutathione Deficiency in Cardiac Patients Is Related to the Functional Status and Structural Cardiac Abnormalities

International audienceBACKGROUND: The tripeptide glutathione (L-gamma-glutamyl-cysteinyl-glycine) is essential to cell survival, and deficiency in cardiac and systemic glutathione relates to heart failure progression and cardiac remodelling in animal models. Accordingly, we investigated cardiac and blood glutathione levels in patients of different functional classes and with different structural heart diseases. METHODS: Glutathione was measured using standard enzymatic recycling method in venous blood samples obtained from 91 individuals, including 15 healthy volunteers and 76 patients of New York Heart Association (NYHA) functional class I to IV, undergoing cardiac surgery for coronary artery disease, aortic stenosis or terminal cardiomyopathy. Glutathione was also quantified in right atrial appendages obtained at the time of surgery. RESULTS: In atrial tissue, glutathione was severely depleted (-58%) in NYHA class IV patients compared to NYHA class I patients (P = 0.002). In patients with coronary artery disease, this depletion was related to the severity of left ventricular dysfunction (P = 0.006). Compared to healthy controls, blood glutathione was decreased by 21% in NYHA class I patients with structural cardiac disease (P<0.01), and by 40% in symptomatic patients of NYHA class II to IV (P<0.0001). According to the functional NYHA class, significant depletion in blood glutathione occurred before detectable elevation in blood sTNFR1, a marker of symptomatic heart failure severity, as shown by the exponential relationship between these two parameters in the whole cohort of patients (r = 0.88). CONCLUSIONS: This study provides evidence that cardiac and systemic glutathione deficiency is related to the functional status and structural cardiac abnormalities of patients with cardiac diseases. These data also suggest that blood glutathione test may be an interesting new biomarker to detect asymptomatic patients with structural cardiac abnormalities