Nicolas Preumont

Myocardial Homing of Nonmobilized Peripheral‐Blood CD34+ Cells After Intracoronary Injection

Granulocyte– colony‐stimulating factor administered for autologous hematopoietic stem cell isolation from blood may favor restenosis in patients implanted after acute myocardial infarction (AMI). We therefore tested the isolation of peripheral‐blood CD34+ cells without mobilization in six patients with AMI. After large‐volume cytapheresis and positive CD34+ cell selection, 3.6 to 27.6 million CD34+ cells were obtained. We performed intra‐coronary implantation of these cells and recorded no restenosis or arrhythmia. We used positron emission tomography (PET) to assess myocardial‐labeled CD34+ cell homing, which accounted for 5.5% of injected cells 1 hour after implantation. In conclusion, large amounts of CD34+ cells, in the range reported in previous studies, can be obtained from nonmobilized peripheral blood. PET with [18F]‐fluorodeoxyglucose cell labeling is an efficient imaging method for homing assessment.

Robotic-enhanced biventricular resynchronization: An alternative to endovenous cardiac resynchronization therapy in chronic heart failure

BACKGROUND Cardiac resynchronization therapy (CRT) by pacing the left and right ventricles is an emerging option for treatment of severe heart failure with ventricular conduction disturbances. Stimulation through a coronary vein is currently the technique of choice to achieve left ventricular (LV) pacing. Unfortunately, this approach carries significant limitations and drawbacks. Therefore we explored robotic-enhanced thoracoscopic implantation of an epicardial lead as an alternative technique to stimulate the LV in cardiac resynchronization therapy. METHODS A total of 15 patients were included in this study. Right (atrial and ventricular) leads were implanted classically through the left subclavian vein. Robotic-enhanced thoracoscopy was then performed to implant the LV epicardial lead. RESULTS Of the 15 patients, 13 underwent successful endoscopic robotic cardiac resynchronization therapy. Two patients underwent conversion to a small thoracotomy. No perioperative complication occurred in the patients who did not undergo conversion. Acute and chronic LV lead thresholds were satisfactory in all patients, improving over time. All were subjectively and objectively improved at 4 months. As compared with conventional methods, the procedural cost was not significantly affected. CONCLUSIONS Based on this feasibility study, we believe that robotic LV epicardial lead implantation is a valuable option to achieve biventricular resynchronization therapy. It allows for more reproducible acute thresholds for LV pacing and sensing than does the percutaneous approach; enables fine tuning of the LV lead position, thus potentially providing optimal hemodynamic benefit; and avoids the pitfalls and limitations of the endovenous approach. Therefore it deserves further prospective studies to assess its place in the therapeutic armamentarium against heart failure.

Absence of nitrate tolerance after long-term treatment with ramipril: an endothelium-dependent mechanism.

To determine whether nitrate tolerance is attenuated on aortas isolated from rats treated in the long term with an angiotensin-converting enzyme (ACE) inhibitor, five groups of rats were studied in parallel. Group 1 received ramipril, 1 mg/ kg/day, p.o., for 6 weeks; group 2 received ramipril at the same dose for 4 weeks, and the last 2 weeks, a cotreatment with ramipril plus HOE 140 (a bradykinin B2 antagonist, 500 microg/ kg/day, s.c. injections); group 3 received losartan, 2 mg/kg/day, p.o., for 6 weeks; group 4 received losartan at the same dose, and the last 2 weeks, a cotreatment with losartan plus HOE 140; and group 5 served as control. Rings of thoracic aorta from these groups were studied in organ baths. After nitroglycerin preincubation (10 microM for 30 min) in vitro, the dose-response curves to nitroglycerin were significantly shifted to the right in the control group but not in group 1. This protective effect was partially present in group 3; it was completely abolished in groups 2 and 4. In groups 1 and 3, it also was abolished after nitric oxide synthase (cNOS) inhibition (L-NMMA incubation) or removal of the endothelium. Superoxide anion accumulation (assessed by lucigenin chemiluminescence) was increased by nitroglycerin incubation in the control group but not in groups 1 and 3. After in vivo exposure to nitroglycerin (50 mg/kg subcutaneously twice daily for 4 days), this protection against nitrate tolerance also was observed in groups 1 and 3. Thus long-term ACE inhibition prevents nitrate tolerance by an endothelium-dependent mechanism involving mainly an enhanced NO availability via B2-kinin receptor. This effect on the cNOS pathway seems to attenuate the superoxide anion accumulation induced by nitroglycerin exposure (probably via a downregulation of oxidative enzyme).

Acute effects of nicotine on arterial stiffness and wave reflection in healthy young non-smokers.

1 Recently, we have demonstrated that cigarette smoke exposure proportionally increases plasma nicotine levels and arterial wave reflection to the aorta. However, the exact contribution of nicotine to the smoke‐induced enhancement of wave reflection and the potential underlying mechanisms have not been fully investigated. 2 The present study was a prospective study in 15 healthy male non‐smokers. All received a placebo and a 2 mg nicotine tablet, according to a randomized double‐blind cross‐over study design. Each subject underwent repeated measurements at baseline and for 1 h after nicotine or placebo intake, using carotid–femoral pulse wave velocity (PWV) to assess arterial compliance. Concurrently, aortic pressures and the augmentation index were evaluated using applanation tonometry. 3 Plasma nicotine concentrations achieved 1 h after intake of the nicotine tablet reached comparable levels to those achieved after 1 h exposure to passive smoke (3.6 ± 0.4 vs 3.2 ± 0.4 ng/mL, respectively; P = 0.4). 4 Nicotine enhanced arterial wave reflection to the aorta, as assessed by the augmentation index corrected for heart rate (4.2 ± 1.3 vs–0.7 ± 0.8% with placebo; P = 0.001). In addition, a progressive increase in carotid–femoral PWV was noted after nicotine administration (0.3 ± 0.1 vs–0.02 ± 0.1 m/s with placebo; P = 0.04). This remained significant even after adjustment for changes in mean blood pressure and heart rate (P = 0.01). 5 Plasma nicotine concentrations comparable to those achieved after exposure to passive smoke enhance arterial wave reflection to the aorta. This is accompanied by an increase in carotid–femoral PWV, denoting a deterioration of arterial compliance by nicotine.

Pulmonary vein isolation by robotic-enhanced thoracoscopy for symptomatic paroxysmal atrial fibrillation.

BACKGROUND Pulmonary vein isolation (PVI) has been shown to be effective treatment of patients with symptomatic paroxysmal atrial fibrillation (PAF). The percutaneous approach is currently the technique of choice. Unfortunately, this procedure has limitations and complications that lead to fluctuating success rates. We explored an alternative technique of robotic-enhanced, closed-chest PVI with an endoscopic microwave-based catheter. METHODS Seven symptomatic PAF patients were included in the study. The pulmonary veins were isolated through right (only) robotic-enhanced thoracoscopy on the beating heart. RESULTS Six patients underwent successful endoscopic PVI. In 1 patient the operation was converted into small right thoracotomy. Operative assessment of the ablation line showed a successful electric block in every patient. Three months after the procedure, the first 5 patients were in permanent sinus rhythm. The 2 other patients had AF but had less frequent and less symptomatic episodes compared with the preoperative situation. CONCLUSIONS On the basis of this preliminary experience, we believe that in the near future endoscopic right-chest robotic-enhanced PVI on the beating heart may become a valid option in the treatment of symptomatic PAF patients. This procedure allows for more-reproducible ablation lines and may avoid many of the pitfalls and drawbacks of the percutaneous approach. Therefore this technique deserves larger prospective evaluation in the treatment of AF.

High prevalence of nocturnal arterial hypertension and non-dipping in lung transplant recipients.

OBJECTIVE An abnormal circadian blood pressure (BP) profile is associated with adverse cardiovascular and all-cause outcomes. It is highly prevalent after heart, liver and kidney transplantation. We aimed to assess the prevalence of an abnormal ambulatory BP pattern in lung transplant recipients (LTx). METHODS Ambulatory BP monitoring (ABPM) was performed in 53 LTx and compared to those of 42 control subjects matched for age, gender and daytime BP. In 19 patients in whom at least two recordings were performed, we compared the first and the last one. RESULTS The non-dipping pattern (a less than 10% reduction in nocturnal BP) was more prevalent in LTx than in control subjects (89 versus 64%, P < 0.01). Nighttime BP was higher in LTx than in control subjects (P < 0.01 and < 0.001 for systolic BP (SBP) and diastolic BP (DBP), respectively). The nocturnal reduction of BP was lower in LTx than in control subjects (3 versus 8% for SBP and 6 versus 13% for DBP, both P < 0.001). These results remained significant after adjustment for the presence of diabetes mellitus and creatinine clearance. In the 19 patients in whom ABPM was performed twice (mean interval between the two recordings was 22 months), ambulatory BP values remained unchanged between the two recordings, although the number of antihypertensive agents was significantly higher. CONCLUSION An abnormal circadian BP profile is highly prevalent after lung transplantation. It is observed consistently over prolonged periods of time.

Assessment of coronary flow reserve by transesophageal echocardiography in cardiac transplant recipients

This study investigated the feasibility of dipyridamole Doppler transesophageal echocardiography to assess coronary flow reserve in 26 patients with orthotopic heart transplantation and compared it with positron emission tomography. We found an 85% success rate in obtaining Doppler flow signals in the proximal left anterior descending coronary artery. Our data also showed that the correlation between transesophageal echocardiography and dipyridamole N-13 ammonia positron emission tomography increases when respective resting rate-pressure products are taken into account. However, comparison between the two methods should be made with caution because coronary flow reserve derived from transesophageal echocardiography tends to be higher than that obtained with positron emission tomography.

Acute myocardial infarction in early postpartum

We present a case of acute anterior myocardial infarction in a breastfeeding woman, 10 days after delivery. The presumed cause was proximal left anterior artery vasospasm, induced by a combination of smoking a first cigarette in the early morning and salbutamol inhalation, in the particular context of peripartum. We discuss briefly the epidemiology, pathophysiology, risk factors, diagnosis, treatment and prognosis of myocardial infarction related to pregnancy and the postpartum period.

Effect of long-term angiotensin II type I receptor antagonism on peripheral and coronary vasomotion.

Angiotensin II, via AT1 receptors plays a key role in endothelial dysfunction and therefore, in atherogenesis. In order to assess whether long-term blockade of these receptors improve peripheral and coronary endothelial function, 13 patients were treated by candesartan cilexetil (AT2B, 16 mg/d in 10 patients and 8 mg in 3). Flow-mediated dilation (FMD, measured with ultra-sound technique) in the brachial artery and cold pressor testing (CPT)-induced changes in myocardial blood flow (MBF, measured with positron emission tomography) were assessed before and after a 6 month treatment period. AT2B did not alter FMD: 5.0 ± 1.2% vs. 6.4 ± 0.9% after treatment. MBF increased significantly during CPT before and after AT2B. Although AT2B did not significantly modify heart rate and blood pressure, MBF normalized to the rate pressure product (MBF/RPP × 10000) was significantly higher and this change remained significant during CPT: it increased from 0.94 ± 0.05 ml/g/min to 1.14 ± 0.09 ml/g/min after AT2B (P < .05) and did not decrease during CPT (1.12 ± 0.08 ml/g/min). Moreover, these AT2B-induced changes in normalized MBF were significantly correlated with the changes in FMD (r = 0.66, P < 0.05).Thus, long-term AT2B improves coronary vasomotion. Although no significant alteration in peripheral conduit endothelial function has been observed, treatment-induced FMD changes seem to be a predictor of coronary circulation improvement.

A new method for real-time co-registration of 3D coronary angiography and intravascular ultrasound or optical coherence tomography

We present a new clinically practical method for online co-registration of 3D quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS) or optical coherence tomography (OCT). The workflow is based on two modified commercially available software packages. Reconstruction steps are explained and compared to previously available methods. The feasibility for different clinical scenarios is illustrated. The co-registration appears accurate, robust and induced a minimal delay on the normal cath lab activities. This new method is based on the 3D angiographic reconstruction of the catheter path and does not require operators identification of landmarks to establish the image synchronization.