J.C. Eicher

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<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. (Funded by the French Ministry of Health; CLOSE ClinicalTrials.gov number, NCT00562289.)

Antioxidative properties of pyruvate and protection of the ischemic rat heart during cardioplegia.

Formation of oxygen free radicals during heart transplantation seems to be related to the alterations occurring during ischemia and reperfusion and could explain the short preservation time of donor hearts. The aim of our study was (a) to analyze the protective effects of pyruvate during cold cardioplegia and ischemia/reperfusion sequence, and (b) to investigate in vitro the radical scavenging properties of this compound. After 30 min of perfusion, isolated working rat hearts were arrested by cardioplegic solution, stored 4 h in B21 solutions at 4 degrees C, and reperfused with Krebs-Henseleit buffer for 45 min. Pyruvate (2 mM) was added to Krebs-Henseleit, cardioplegic, and storage solutions, and functional parameters were recorded throughout the experiments. In a second part, control hearts and hearts treated with pyruvate were cannulated via the aorta and perfused for 30 min by the Langendorff method, arrested by cardioplegic solution, stored 4 h in B21 solutions at 4 degrees C, and reperfused for 45 min by the Langendorff method. Malonedialdehyde and alpha-tocopherol levels were determined on heart homogenate. In situ detection of apoptotic cells also was performed on tissue samples (left ventricle) at the end of the ischemia/reperfusion sequence. To demonstrate in vitro the antioxidant effects of pyruvate, we monitored (a) its hydroxyl radical scavenging properties by using electron paramagnetic resonance (EPR) spectroscopy, and (b) the decrease of fluorescence of allophycocyanin, in the presence of a Fenton system (H2O2/Cu2+). Ischemia for 4 h, followed by myocardial reperfusion, resulted in substantially reduced mechanical function. Hearts subjected to this ischemia and pretreated with pyruvate showed a significant improvement in the function recovery. After the ischemia/reperfusion protocol, no significant decrease of malonedialdehyde levels was shown on hearts treated with pyruvate. However, alpha-tocopherol levels were higher in the pyruvate group compared with the control group. At the end of the reperfusion period, levels of apoptotic cells were significantly lower in hearts treated with pyruvate compared with control hearts. EPR studies showed that pyruvate was an efficient hydroxyl scavenger, with a median inhibitory concentration (IC50) of 8 mM. The allophycocyanin assay also showed a dose-dependent effect of pyruvate against hydroxyl radicals. In conclusion, these findings showed that pyruvate could prevent reperfusion injuries in the isolated heart, probably by its antioxidative properties. The application of pyruvate may contribute to the preservation of hearts for organ transplantation.

Isolated left ventricular non-compaction in adults: clinical and echocardiographic features in 105 patients. Results from a French registry

The clinical features, prognosis, and even definition of left ventricular non‐compaction (LVNC) are still the subject of much debate. The aim of this registry was to describe the clinical, echocardiographic, and prognostic features of LVNC in France. The main endpoint was to assess clinical and echocardiographic predictors of adverse outcome, defined as death or heart transplantation.

Effects of low-frequency electrical stimulation of quadriceps and calf muscles in patients with chronic heart failure.

PURPOSE The aim of this preliminary study was to evaluate the effects of low-frequency electrical stimulation of quadriceps and calf muscles on global exercise capacities, skeletal muscle metabolism, calf muscle volume, and cardiac output in patients with chronic heart failure. METHODS Fourteen patients with chronic heart failure (mean age of 56.4 years +/- 9.1 SD; mean radionuclide left ventricular ejection fraction of 22.3% +/- 8.8 SD) underwent 5 weeks (1 hour per day, 5 days per week) of low-frequency electrical stimulation of quadriceps and calf muscles. RESULTS Low-frequency electrical stimulation was well tolerated. Exercise capacity and the calf muscles volumes increased significantly after rehabilitation in comparison with prior rehabilitation (the peak oxygen consumption increased from 17.2 mL/(kgmin) +/- 5.3 SD to 19.6 mL/(kgmin) +/- 5.9 SD; the anaerobic threshold increased from 12.3 mL/(kgmin) +/- 3.2 SD to 15.2 mL/(kgmin) +/- 3.3 SD; the 6-minute walking test increased from 419 m +/- 122 SD to 459 m +/- 114.3 SD; the gastrocnemius volume increased from 259.4 cm3 +/- 58 SD to 273.4 cm3 +/- 74 SD, and the soleus volume increased from 319 cm3 +/- 42.9 SD to 338 cm3 +/- 52.5 SD). The New York Heart Association class was improved after rehabilitation. The P-31 nuclear magnetic resonance spectroscopy of gastrocnemius muscle data were not significantly modified after rehabilitation, thereby inferring that no significant improvement of the muscle metabolism occurred. These data reinforce the hypothesis of an increased muscle mass during stimulation. It is noteworthy that the electrical stimulation did not increase cardiac output at any stage; an enormous asset in favor of this mode of rehabilitation. CONCLUSION These results suggest that low-frequency muscular electrical stimulation is well tolerated, induces an increased exercise capacity in patients with chronic heart failure, without an undesirable increase in cardiac output.

Current aspects of the spectrum of acute heart failure syndromes in a real-life setting: the OFICA study.

To improve knowledge of epidemiological data, management, and clinical outcome of acute heart failure (AHF) in a real‐life setting in France.

Hypoxaemia associated with an enlarged aortic root: a new syndrome?

Objective: To assess the mechanisms through which an enlarged aortic root may facilitate right to left shunting through a patent foramen ovale. Patients: 19 patients with the platypnoea-orthodeoxia syndrome (POS) were compared with 30 control patients without platypnoea. Interventions: Multiplane transoesophageal echocardiography. Main outcome measures: The aortic root diameter, atrial septal dimension behind the aortic root, and amplitude of the phasic oscillation of the septum were measured. Four groups of patients were compared: 12 platypnoeic patients with a dilated aortic root (POS-D), 7 platypnoeic patients with a normal aortic root (POS-N), 15 control patients with a dilated aortic root (CONT-D), and 15 control patients with a normal aortic root (CONT-N). Results: In POS-D and CONT-D patients, the apparent atrial septal dimension was 16.3 (2.7) mm and 17.4 (5.9) mm respectively, compared with 24.4 (5.2) mm in POS-N patients and 25 (4) mm in CONT-N (p < 0.005). Furthermore, the amplitude of septal oscillation was 14.7 (2.5) mm in the POS-D group versus 5.8 (2.4) mm in CONT-N (p < 0.001) compared with 23.3 (3) mm in seven patients with an atrial septal aneurysm (p <0.001). Conclusion: Patients with an enlarged aorta have an apparently smaller dimension and increased mobility of the atrial septum. These findings appear to result from compression by the aortic root and decreased septal tautness. Consequently, a “spinnaker effect” with the inferior vena caval flow may take place, opening the foramen ovale and leading to sustained right to left shunting.

Atrial dyssynchrony syndrome: an overlooked phenomenon and a potential cause of ‘diastolic’ heart failure

The purpose of the present study was too explore the role of interatrial dyssynchrony in heart failure with preserved ejection fraction (HFPEF).

Intra-Dialytic Electrostimulation of Leg Extensors May Improve Exercise Tolerance and Quality of Life in Hemodialyzed Patients

Hemodialyzed (HD) patients with end-stage renal disease (ESRD) exhibit lower fitness as a consequence of chronic uremic changes that trigger various structural, metabolic, and functional abnormalities in skeletal muscles. The aim of this randomized study was to compare the effect of rehabilitation (RHB) training on a bicycle ergometer and electromyostimulation (EMS) of leg extensors in HD patients with ESRD. Thirty-two HD patients (18 men/14 women; mean age 61.1 ± 8.8 years) were randomized into three groups: (i) exercise training (ET; n = 11) on bicycle ergometer 2 × 20 min; (ii) EMS (n = 11) where stimulation (10 Hz) of leg extensors was applied for 60 min; and (iii) controls (CON; n = 10) without exercise. Exercising was performed between the 2nd and the 3rd hour of HD, three times a week, 20 weeks in total. Ergometric test was performed in order to evaluate peak workload (W(peak)), 6-min corridor walking test (CWT) to evaluate the distance walked, and dynamometry of leg extensors to assess muscle power (F(max)). Urea clearance was monitored and expressed as standard parameters: spKt/V, spKt/V equilibrated (spKt/V-e), and the urea removal ratio (URR). Quality of life (QoL) was assessed by the questionnaire SF-36. A significant increase of F(max) (P = 0.040 in group ET; P = 0.032 in group EMS), of 6-min CWT (P < 0.001 in ET group; P = 0.042 in EMS group), and of W(peak) (P = 0.041 in ET group) was observed. In both exercising groups, significant increase of spKt/V, spKt/V-e, and URR was found as compared with initial values (P < 0.05). In both exercising groups, highly significant changes in summarized mental functions were found (P = 0.001); in summarized physical components, significant improvement was observed in the ET group (P = 0.006). Intradialytic RHB showed comparable positive effects on functional parameters, urea clearance, and QoL. Intradialytic EMS might represent wide therapeutic possibility in the near future.

Electrical Stimulation of Skeletal Muscles

The aim of this study was to investigate whether electrical stimulation of skeletal muscles could represent a rehabilitation alternative for patients with chronic heart failure (CHF). Thirty patients with CHF and NYHA class II-III were randomly assigned to a rehabilitation program using either electrical stimulation of skeletal muscles or bicycle training. Patients in the first group (n = 15) had 8 weeks of home-based low-frequency electrical stimulation (LFES) applied simultaneously to the quadriceps and calf muscles of both legs (1 h/day for 7 days/week); patients in the second group (n = 15) underwent 8 weeks of 40 minute aerobic exercise (3 times a week). After the 8-week period significant increases in several functional parameters were observed in both groups: maximal VO2 uptake (LFES group: from 17.5 +/- 4.4 mL/kg/min to 18.3 +/- 4.2 mL/kg/min, P < 0.05; bicycle group: from 18.1 +/- 3.9 mL/kg/min to 19.3 +/- 4.1 mL/kg/min, P < 0.01), maximal workload (LFES group: from 84.3 +/- 15.2 W to 95.9 +/- 9.8 W, P < 0.05; bicycle group: from 91.2 +/- 13.4 W to 112.9 +/- 10.8 W, P < 0.01), distance walked in 6 minutes (LFES group: from 398 +/- 105 m to 435 +/- 112 m, P < 0.05; bicycle group: from 425 +/- 118 m to 483 +/- 120 m, P < 0.03), and exercise duration (LFES group: from 488 +/- 45 seconds to 568 +/- 120 seconds, P < 0.05; bicycle group: from 510 +/- 90 seconds to 611 +/- 112 seconds, P < 0.03). These results demonstrate that an improvement of exercise capacities can be achieved either by classical exercise training or by home-based electrical stimulation. LFES should be considered as a valuable alternative to classical exercise training in patients with CHF.

Possible association of thrombotic, nonbacterial vegetations of the mitral ring-mitral annular calcium and stroke.

Although numerous studies have shown an increased risk of stroke associated with mitral annular calcification, a direct link has rarely been demonstrated. We report the occurrence of long, pedunculated thrombi attached to the calcified mitral annulus in 3 patients who suffered from stroke, with resolution after anticoagulant and antithrombotic therapy.