Samuel Lévy

Effects of nicardipine on pulmonary and systemic vascular reactivity to oxygen in patients with pulmonary hypertension secondary to chronic obstructive lung disease.

Summary: We compared the acute effects of nicardipine and a placebo on the response of pulmonary and systemic circulation to different inspiratory fractional concentrations of O2 (FiO2) in 10 patients with pulmonary hypertension secondary to chronic obstructive lung disease. After catheterization of the pulmonary and femoral arteries, gas mixtures containing 15, 21, and 30% O2 were randomly administered for 20 min each during infusion of saline and then nicardipine (0.06 mg/kg/min). Plasma nicardipine level was maintained at 30 ng/ml. During nicardipine infusion, cardiac index (CI) was significantly higher (+20%, p < 0.05) than during placebo infusion, with no change in mean pulmonary artery pressure (MPAP). Pulmonary resistances also decreased significantly (– 20%) during nicardipine. No change in arterial or mixed venous O2 contents was noted. Mean arterial pressure (MAP) and systemic resistances decreased significantly with nicardipine. Inhaling a hyperoxic mixture was followed by a significant decrease in arterial pressure during placebo infusion; this was not observed during nicardipine. In contrast with systemic circulation, the response of the pulmonary circulation to different FiO, levels was unaffected by nicardipine.

Newer clinically available antithrombotics and their antidotes

New oral anticoagulants (NOACs) have emerged as an alternative therapy to warfarin in the treatment of arterial and venous thromboembolism and in stroke prevention in patients with non-valvular atrial fibrillation (AF). Three of them, i.e., dabigatran, rivaroxaban, and apixaban, have been approved for clinical use in North America and in a number of European countries. In non-valvular AF, their approval was based on large randomized trials showing that they are non-inferior or even, in some instances, superior to warfarin. Dabigatran is a direct thrombin (factor IIa) inhibitor; rivaroxaban and apixaban are direct factor Xa inhibitors. Before using NOACs, it is recommended to become familiar with their pharmacological characteristics and their metabolism. The absence of specific antidotes is often cited as part of the possible weaknesses of NOACs. Antidotes are perceived to be useful in emergency situations such as life-threatening bleeding or non-elective major surgery. NOACs do not require blood monitoring, and therefore, patient compliance to the treatment is essential. For the present time, there are no specific antidotes available for the three NOACs approved for clinical use. However, phase I or phase II research studies in this area are ongoing. For dabigatran, a specific antidote has been tested in a rat model of anticoagulation, and a study in healthy male volunteers has been recently reported. For rivaroxaban, prothrombin complex concentrates (PCCs) have been found to completely reverse the prolongation of the prothrombin time induced by this NOAC. For apixaban, recombinant factor VII was found in an experimental study using human blood to be superior to activated PCC (aPCC) and PCC. More specific antidotes for rivaroxaban and apixaban are in phases I and II evaluation. The management of patients suffering from a major bleeding or requiring a non-elective major surgery includes non-specific reversal agents and is discussed in the light of a recent position paper and of current literature. Most recommendations are based on expert opinions only as randomized trials using agents for reversal of anticoagulation in case of life-threatening bleeding or of major urgent surgery are not available.

Nifedipine inhibits the effects of almitrine in patients suffering from pulmonary artery hypertension secondary to chronic obstructive pulmonary disease

It has been suggested that almitrine improves the local ventilation/perfusion ratio by enhancing hypoxic pulmonary vasoconstriction (HVC), leading to an increase in pulmonary vascular resistance (PVR) and PaO2. The goal of the present study was to determine if pulmonary vasodilation induced by nifedipine inhibits the enhancement of HVC (and consequently of PaO2), in patients suffering from chronic obstructive pulmonary disease (COPD). Two groups of 10 patients were compared in a controlled, double-blind study. Hemodynamics and blood gases were measured during continuous infusion of placebo or almitrine (8 μg/kg/min). Two hours after the onset of the infusion, a single dose of nifedipine (10 mg) was given sublingually. Almitrine infusion was followed by an increase in PaO2 (20%) and PVR (48%). In the almitrine group, after nifedipine, the PVR decreased 33% and PaO2 dropped to baseline while in the placebo group the PVR decreased 22% and PaO2 fell to 11% below base-line. In COPD patients, nifedipine inhibits almitrine-induced pulmonary vasoconstriction.

Clinical presentation of inappropriate sinus tachycardia and differential diagnosis

Inappropriate sinus tachycardia (IST) is a syndrome characterized by a sinus tachycardia not related to a medical condition, to a physiological response, or to medication or drugs and associated with symptoms, often invalidating and altering the quality of life of affected patients. It occurs predominantly in adolescents and young adults, and in the female sex. The diagnosis requires a complete work-up in order to exclude other causes of sinus tachycardia and one or several additional tests: 24-h ECG ambulatory recordings, echocardiogram, exercise testing, and autonomous nervous system assessment. It should be differentiated from the postural orthostatic tachycardia syndrome, with which it shares a number of symptoms, and other supraventricular tachycardias originating in the high right atrium. An electrophysiological study should be considered in selected cases in order to differentiate IST from other supraventricular tachycardias. The mechanism is still unclear, and possible etiologies may include intrinsic abnormality of the sinus node, autonomic dysfunction, hypersensitivity of the sinus node to catecholamines, blunted vagal system, or a combination of the above. The authors emphasize the wide spectrum of clinical presentations and the need to better define the IST and the criteria required to ascertain its diagnosis.

Changing epidemiology of atrial fibrillation.

This editorial refers to ‘Incidence and prevalence of atrial fibrillation: an analysis based on 8.3 million patients’ by T. Wilke et al. , on page 486 In recent years, atrial fibrillation (AF) has received increased attention as it has been recognized as a major risk factor for stroke, mortality, and haemodynamic complications. Atrial fibrillation is associated with (often debilitating) symptoms and poor quality of life. The results of the European Community Stroke Project study have suggested that strokes associated with AF conferred greater mortality at three months compared with strokes not related to AF (32.8 vs. 19.9%; P < 0.001).1 Furthermore, AF increased the likelihood of severe disability [odds ratio (OR) 1.43, 95% confidence interval (CI) 1.13–1.80] or handicap (OR 1.51, 95% CI 1.13–2.02).2 In addition, the cost associated with AF and related hospitalizations is high.3 Therefore, the improved knowledge of AF epidemiology is of utmost importance. The incidence and prevalence of this increasingly common arrhythmia has been the subject of a number of reports in the past decades. In 1956, Katz and Pick4 evaluated the prevalence of AF among 50 000 consecutive patients undergoing an electrocardiogram (ECG) and found 1543 patients (3.0%) with paroxysmal AF and 4316 with chronic AF (8.6%). …

Pulmonary vein isolation using a single size cryoballoon chosen according to transesophageal echocardiography information

BACKGROUND Pulmonary vein isolation (PVI) using cryoballoon (CB) catheter is a new technique for atrial fibrillation (AF) ablation. Previous studies used computer tomography (CT) or magnetic resonance imaging (MRI) scan to determine the pulmonary vein (PV) diameter and anatomy for choosing the CB size. We evaluated pre-ablation transoesophageal-echocardiography (TEE) as an alternative to CT/MRI scan in patients undergoing AF ablation for determining the appropriate size of the CB. METHODS Fifty-five consecutive patients (men=43, women=12) with a mean age of 63 ± 12.5 years, and with drug-refractory paroxysmal AF (34 patients) or persistent AF (21 patients) were included in this prospective study. All patients underwent pre-ablation TEE. RESULTS Hypertension was present in 19 patients (34%). Mean anterior-posterior left atrium diameter was 45.1 ± 8.9 mm. In total, 217 PV were targeted using a single 23-mm (n=14) or 28-mm (n=40) CB catheter chosen according to TEE-obtained measurements. PVI was achieved in 195 PV (90%). Mean number of CB applications per patient was 9.8 ± 2.1 (range 8-14). Mean procedure duration and fluoroscopy times were 131 ± 27 min (90-190 min) and 36 ± 12 min (22-66 min) respectively. Phrenic nerve palsy occurred in 3 patients (5.4%) and was transient (<1 month) in all of them. CONCLUSION This study suggests that TEE is an easily available and effective tool to select the size of the CB for PVI according to evaluated PV diameters and anatomy.

Bundle branch blocks and/or hemiblocks complicating acute myocardial ischemia or infarction

Despite the bulk of anatomical and histologic evidence supporting the existence of three fascicules in the left branch of the His bundle, the concept of a bifascicular system proposed by Rosenbaum and his school has been adopted by the cardiological community as a practical teaching tool. Left anterior hemiblock (LAH) refers to block of the antero-superior branch of the left branch which is small and left posterior hemiblock (LPH) to block of the postero-inferior branch which is larger. The LAH is more common that the LPH and often associated with a complete right bundle branch block (RBBB). Coronary artery disease (CAD) is a major cause of hemiblocks. In this review article, we discuss various aspects of the relation of hemiblocks with CAD. We looked at the prevalence of LAH in consecutive patients undergoing coronary angiography and who had a significant coronary lesion in one vessel or more. In all patients with LAH, a significant lesion of the left anterior descending coronary artery was present, with in the majority of patients, an impairment of the left ventricular function. Bifascicular block (RBBB with LAH or LPH) can complicate acute myocardial infarction and is often associated with a poor prognosis and the presence of heart failure. Thrombolysis and or early angioplasty in acute myocardial infarction have significantly improved the prognosis and reduced the mortality associated with bifascicular block. Left anterior hemiblock pattern was also observed during angina pectoris occurring at rest or induced by exercise or atrial pacing. In these circumstances, LAH is transient and is likely to be due to ischemia in the anterolateral wall related to a lesion of the main trunk or the proximal left anterior descending coronary artery with the postero-inferior wall being first depolarized. The presence of bifascicular block in acute myocardial infarction still is associated with an unfavorable prognosis as compared to non-bundle branch block patients because of the common association with heart failure and other comorbidities.

Simultaneous pulmonary vein cryoablation and cavotricuspid isthmus radiofrequency ablation in patients with combined atrial fibrillation and typical atrial flutter

Pulmonary vein isolation (PVI) using cryoballoon (CB) technique and cavotricuspid isthmus (CTI) ablation using radiofrequency (RF) are established interventions for drug-resistant atrial fibrillation (AF) and typical atrial flutter (AFL). Twelve patients with a mean age of 62 ± 12 years underwent simultaneous delivery of RF energy at the CTI during CB applications at the PV ostia. Pulmonary vein isolation was achieved in all PVs and sustained bidirectional CTI conduction block obtained in all patients. The reported ablation protocol of combined paroxysmal AF and typical AFL did not result in prolongation of the procedure duration or in prolonged radiation exposure when compared to CB-PVI alone. No interferences between both ablation energy systems were observed. These preliminary results suggest that combined paroxysmal AF and typical AFL can be successfully and safely ablated using hybrid energy sources with simultaneous CTI ablation using RF during CB applications at the PV ostia.