Hervé Le Breton

Acute hemodynamic effects of biventricular DDD pacing in patients with end-stage heart failure

OBJECTIVES The aim of this study was to assess the potential acute benefit of multisite cardiac pacing with optimized atrioventricular synchrony and simultaneous biventricular pacing in patients with drug-refractory congestive heart failure (CHF). BACKGROUND Prognosis and quality of life in severe CHF are poor. Various nonpharmacological therapies have been evaluated but are restricted in their effectiveness and applications. In the early 1990s, dual chamber pacing (DDD) pacing was proposed as primary treatment of refractory CHF but results were controversial. Recently, tests to evaluate the effect of simultaneous pacing of both ventricles have elicited a significant improvement of cardiac performance. METHODS Acute hemodynamic study was conducted in 18 patients with severe CHF (New York Heart Association class III and IV) and major intraventricular conduction block (IVCB) (QRS duration = 170+/-37 ms). Using a Swan-Ganz catheter, pulmonary artery pressure, pulmonary capillary wedge pressure (PCWP) and cardiac index (CI) were measured in different pacing configurations: atrial pacing (AAI) mode, used as reference, single-site right ventricular DDD pacing and biventricular pacing with the right ventricular lead placed either at the apex or at the outflow tract. RESULTS The CI was significantly increased by biventricular pacing in comparison with AAI or right ventricular (RV). DDD pacing (2.7+/-0.7 vs. 2+/-0.5 and 2.4+/-0.6 l/min/m2, p < 0.001). The PCWP also decreased significantly during biventricular pacing, compared with AAI (22+/-8 vs. 27+/-9 mm Hg; p < 0.001). CONCLUSIONS This acute hemodynamic study demonstrated that biventricular DDD pacing may significantly improve cardiac performance in patients with IVCB and with severe heart failure, in comparison with intrinsic conduction and single-site RV DDD pacing.

Permanent Left Ventricular Pacing With Transvenous Leads Inserted Into The Coronary Veins

This paper describes a preliminary experiment ‐ conducted jointly by 2 centers ‐ of permanent left ventricular pacing using leads inserted by the transvenous route and through the coronary sinus into the cardiac veins of the left ventricle free wall. The aim was to obtain permanent biventricular pacing in a totally endocavitary configuration in pattents with severe LV dysfunction and drug‐refractory heart failure. Two types of leads were used: nonspecific unipolar leads at the beginning of the experiment, followed by leads specifically designed to be used in the coronary sinus in a second step. The electrode could be fitted in an adequate location in 35 of the 47 patients (75.4%), with a 1.15±0.7 V acute pactng threshold and 11.8±5.7 mV R wave amplitude. The success rate was significantly higher with the specific electrodes (81.8% vs 53,3%, p < 0.001). The pacing and sensing thresholds upon implantation were not influenced by the type of lead or by the localization of the cardiac vein that was catheterized (great cardiac vein, lateral vein, postero‐lateral or posterior vein, mid cardiac vein). In contrast, the pacing threshold was significantly lower (0.8 ± 0.2 vs L8 ± 0.8 V; p = 0.002) and the R wave amplitude tended to be greater (13.1 ± 4.5 mV vs 9.3 ± 6.5 mV; p = 0.07) when the tip electrode could be inserted distally into the vein, by comparison with a proximal site near the ostium. At the end of follow‐up (10.2 ± 8.7 months), 34 out of the 35 leads were still fully functional, with a chronic pacing threshold of 1.8 ± 0.7 V and a R wave amplitude of 10.7 ± 6 mV. To conclude, permanent LV pacing via the transvenous route is possible in most patients, with excellent safety and long‐term results.

Immediate vs Delayed Intervention for Acute Coronary Syndromes: A Randomized Clinical Trial

CONTEXT International guidelines recommend an early invasive strategy for patients with high-risk acute coronary syndromes without ST-segment elevation, but the optimal timing of intervention is uncertain. OBJECTIVE To determine whether immediate intervention on admission can result in a reduction of myocardial infarction compared with a delayed intervention. DESIGN, SETTING, AND PATIENTS The Angioplasty to Blunt the Rise of Troponin in Acute Coronary Syndromes Randomized for an Immediate or Delayed Intervention (ABOARD) study, a randomized clinical trial that assigned, from August 2006 through September 2008 at 13 centers in France, 352 patients with acute coronary syndromes without ST-segment elevation and a Thrombolysis in Myocardial Infarction (TIMI) score of 3 or more to receive intervention either immediately or on the next working day (between 8 and 60 hours after enrollment). MAIN OUTCOME MEASURES The primary end point was the peak troponin value during hospitalization; the key secondary end point was the composite of death, myocardial infarction, or urgent revascularization at 1-month follow-up. RESULTS Time from randomization to sheath insertion was 70 minutes with immediate intervention vs 21 hours with delayed intervention. The primary end point did not differ between the 2 strategies (median [interquartile range] troponin I value, 2.1 [0.3-7.1] ng/mL vs 1.7 [0.3-7.2] ng/mL in the immediate and delayed intervention groups, respectively; P = .70). The key secondary end point was observed in 13.7% (95% confidence interval, 8.6%-18.8%) of the group assigned to receive immediate intervention and 10.2% (95% confidence interval, 5.7%-14.6%) of the group assigned to receive delayed intervention (P = .31). The other end points, as well as major bleeding, did not differ between the 2 strategies. CONCLUSION In patients with acute coronary syndromes without ST-segment elevation, a strategy of immediate intervention compared with a strategy of intervention deferred to the next working day (mean, 21 hours) did not result in a difference in myocardial infarction as defined by peak troponin level. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00442949.

AREVA: Multicenter Randomized Comparison of Low-Dose Versus Standard-Dose Anticoagulation in Patients With Mechanical Prosthetic Heart Valves

BACKGROUND Moderate anticoagulation may be proposed to reduce the risk of hemorrhage for certain patients with a mechanical prosthesis, but the consequences for risk of thromboembolism are debated. METHODS AND RESULTS The purpose of the AREVA trial was to compare moderate oral anticoagulation (international normalized ratio [INR] of 2.0 to 3.0) with the usual regimen (INR of 3.0 to 4.5) after a single-valve replacement with a mechanical prosthesis, either Omnicarbon or St Jude. Patients included were between 18 and 75 years old, in sinus rhythm, and with a left atrial diameter < or = 50 mm on the time-motion echocardiogram. Patients were randomized for INR after surgery. From 1991 to 1994, 433 patients underwent valve replacement (aortic, 414; mitral, 19) with 353 St Jude and 80 Omnicarbon prostheses; 380 patients were randomized for INR: 188 for INR 2.0 to 3.0 and 192 for INR 3.0 to 4.5. Mean follow-up was 2.2 years (1 to 4 years). Analysis of 18001 INR samples showed that the mean of the median of INR was 2.74 +/- 0.35 in the 2.0 to 3.0 group and 3.21 +/- 0.33 in the 3.0 to 4.5 group (P < .0001). Thromboembolic events, as assessed from clinical data and CT brain scans, occurred in 10 patients in the 2.0 to 3.0 INR group and 9 patients in the 3.0 to 4.5 INR group (P = .78). Hemorrhagic events occurred in 34 patients in the 2.0 to 3.0 INR group and 56 patients in the 3.0 to 4.5 INR group (P < .01), with 13 and 19 major hemorrhagic events, respectively (P = .29). CONCLUSIONS In selected patients with mechanical prostheses, moderate anticoagulation prevents thromboembolic events as effectively as conventional anticoagulation and reduces the incidence of hemorrhagic events.

Role of Platelets in Restenosis After Percutaneous Coronary Revascularization

The role of platelets in the process of restenosis after percutaneous coronary intervention is not fully understood. After vascular injury there is extensive platelet activation, adhesion, aggregation and secretion. Through the liberation of growth factors, such as platelet-derived growth factor, and surface expression of cell adhesion molecules, such as the glycoprotein IIb/IIIa integrin, platelets appear to be a pivotal mediator of the vascular injury response. Experimental models have demonstrated that profound, prolonged thrombocytopenia, or blockade of the IIb/IIIa receptor, may reduce neointimal hyperplasia after arterial balloon injury. However, multiple clinical trials testing conventional or new platelet agents have not yielded any salutary effects. The recent finding that abciximab, a monoclonal antibody fragment directed against IIb/IIIa, reduced clinical restenosis after coronary angioplasty by 26% in patients raises questions about the mechanism of benefit. The alpha v beta 3 vitronectin receptor is responsible for binding endothelial cells to platelets, and it also has a key role in modulating smooth muscle cell migration. It is possible that the antibody fragment exerts its effect on restenosis by means of alpha v beta 3, because abciximab fully cross-reacts to this integrin owing to the shared beta 3 subunit. To date, the other platelet glycoprotein IIb/IIIa inhibitors, including Integrelin, Tirofiban, Lamifiban and Xemilofiban, are specific in binding to this particular integrin. Considerable further study is necessary to unravel the effects of platelets on the restenosis process.

Effect of the Direct Nitric Oxide Donors Linsidomine and Molsidomine on Angiographic Restenosis After Coronary Balloon Angioplasty The ACCORD Study

BACKGROUND Nitric oxide (NO) donors, in addition to their vasodilator effect, decrease platelet aggregation and inhibit vascular smooth muscle cell proliferation. These actions could have beneficial effects on restenosis after coronary balloon angioplasty. METHODS AND RESULTS In a prospective multicenter, randomized trial, 700 stable coronary patients scheduled for angioplasty received direct NO donors (infusion of linsidomine followed by oral molsidomine) or oral diltiazem. Treatment was started before angioplasty and continued until 12 to 24 hours before follow-up angiography at 6 months. The primary study end point was minimal lumen diameter, assessed by quantitative coronary angiography, 6 months after balloon angioplasty. Clinical variables were well matched in both groups. However, despite intracoronary administration of isosorbide dinitrate, the reference diameter in the NO donor group was significantly greater than in the diltiazem group on the preangioplasty, postangioplasty, and follow-up angiograms. Pretreatment with an NO donor was associated with a modest improvement in the immediate angiographic result compared with pretreatment with diltiazem (minimum luminal diameter, 1.94 versus 1.81 mm; P = .001); this improvement was maintained at the 6-month angiographic follow-up (minimal lumen diameter, 1.54 versus 1.38 mm; P = .007). The extent of late luminal narrowing did not differ significantly between groups (loss index in the NO donor and diltiazam groups, 0.35 +/- 0.78 and 0.46 +/- 0.74, respectively; P = .103). Restenosis, defined as a binary variable (> or = 50% stenosis), occurred less often in the NO donor group (38.0% versus 46.5%; P = .026). Combined major clinical events (death, nonfatal myocardial infarction, and coronary revascularization) were similar in the two groups (32.2% versus 32.4%). CONCLUSIONS Treatment with linsidomine and molsidomine was associated with a modest improvement in the long-term angiographic result after angioplasty but had no effect on clinical outcome. The improved angiographic result related predominantly to a better immediate procedural result, because late luminal loss did not differ significantly between groups.

Prognostic Implications of Pulmonary Hypertension in Patients With Severe Aortic Stenosis Undergoing Transcatheter Aortic Valve Implantation Study From the FRANCE 2 Registry

Background—Pulmonary hypertension (PH) is associated with poor prognosis in patients with severe aortic stenosis. The aim of this multicenter study was to describe clinical outcome after transcatheter aortic valve implantation. Methods and Results—The FRANCE 2 Registry included all patients undergoing transcatheter aortic valve implantation in France in 2010 and 2011. Patients were divided into 3 groups depending on systolic pulmonary artery pressure (sPAP) estimated in transthoracic echocardiography: group I, sPAP <40 mm Hg (no PH); group II, sPAP 40 to 59 mm Hg (mild-to-moderate PH); and group III, sPAP ≥60 mm Hg (severe PH). Patients were followed up for 1 year. A total of 2435 patients whose pre–transcatheter aortic valve implantation sPAP was reported were included. A total of 845 were in group I (34.7%), 1112 in group II (45.7%), and 478 in group III (19.6%). Procedural success, early complications, and 30-day mortality were statistically similar across sPAP groups. One-year mortality was higher in groups II and III (group I, 22%; group II, 28%; and group III, 28%; P=0.032). Mild-to-moderate and severe PH were identified as an independent factor of all-cause mortality. The major adverse cardiovascular event rates did not differ according to sPAP. New York Health Association functional class improved significantly in all groups. Conclusions—PH (sPAP ≥40 mm Hg) in patients with aortic stenosis undergoing transcatheter aortic valve implantation was associated with increased 1-year mortality especially when severe (sPAP ≥60 mm Hg) but not with increased 30-day mortality, and functional status was significantly improved regardless of PAP level.

Antiplatelet therapy in patients with anticoagulants undergoing percutaneous coronary stenting (from STENTIng and oral antiCOagulants [STENTICO]).

We evaluated the safety and efficacy of dual antiplatelet therapy, in association with oral anticoagulant (OAC) therapy, in patients undergoing percutaneous coronary intervention (PCI). The use of this triple therapy increases the rate of adverse outcomes, as shown by retrospective studies. In this first prospective multicenter registry STENTIng and oral antiCOagulation (STENTICO), all patients with OAC therapy undergoing PCI were included and followed up at 2 and 12 months. A total of 359 patients were included from 40 French centers. In 234 (65.2%; group 1) of these 359 patients, OAC therapy was discontinued (22 +/- 31 days). In 125 patients (34.8%; group 2), triple therapy was continued. The baseline characteristics were similar in the 2 groups. In group 2, a radial approach was more often used (65.6% vs 43.8%, p = 0.003), fewer drug-eluting stents were implanted (33.3% vs 24.8%, p = 0.06), and fewer anti-glycoprotein IIb/IIIa antagonists were prescribed (5.6% vs 8.5%, p = 0.02). The stroke rate did not differ significantly, at 3.0% (95% confidence interval 0.8% to 5.2%) for group 1 versus 0.8% (95% confidence interval -0.8% to 2.4%) in group 2. Severe and moderate bleeding, according to the Global Use of Strategies to Open Coronary Arteries (GUSTO) criteria, occurred in 2.1% and 6.4% of groups 1 and 2, respectively (p = 0.04). A significant difference in bleeding risk was found between the femoral and radial approaches (10.3% vs 3.8%, respectively; p = 0.01). In conclusion, adding dual antiplatelet therapy to pre-existing OAC therapy increases the post-PCI bleeding risk. Temporary discontinuation decreased this bleeding risk but tended to increase the risk of stroke. A radial approach for PCI could be a good alternative to the conventional femoral route to avoid bleeding.

Diagnostic contributions of cardiac magnetic resonance imaging in patients presenting with elevated troponin, acute chest pain syndrome and unobstructed coronary arteries

AIMS Myocardial infarction with unobstructed coronary artery disease represents a serious diagnostic challenge. The role of cardiac magnetic resonance in the management of cardiomyopathies is increasing. We examined the diagnostic contributions of cardiac magnetic resonance in patients presenting with acute chest pain syndrome, elevated serum cardiac troponin concentrations and no significant coronary artery stenoses. METHODS Over a 3-year period, 107 consecutive patients (mean age 43.5 years; 62% men) presented to our institution with acute onset of chest pain, elevated serum troponin concentration and unobstructed coronary arteries, and underwent 3-tesla cardiac magnetic resonance at a mean delay of 6.9 days. A diagnosis was made based on: wall motion abnormalities and pericardial effusion on cine mode; myocardial oedema on T2-weighted imaging; abnormalities on first-pass perfusion imaging; and late gadolinium enhancement on T1-weighted imaging. RESULTS Cardiac magnetic resonance was normal in 10.3% of patients and contributed a diagnosis in 89.7%, including myocarditis in 59.9%, stress cardiomyopathy (takotsubo syndrome) in 14% and myocardial infarction in 15.8%. Patients with normal cardiac magnetic resonance had a significantly lower mean peak troponin concentration (2.6ng/mL) than patients with diagnostic cardiac magnetic resonance (9.7ng/mL; P=0.01). CONCLUSION Cardiac magnetic resonance contributed a diagnosis in nearly 90% of patients presenting with acute chest pain, elevated serum troponin and unobstructed coronary arteries.

Permanent Left Atrial Pacing with a Specifically Designed Coronary Sinus Lead

This article reports the original use of a specifically designed coronary sinus (CS) lead for permanent left atrial (LA) pacing. The device is characterized by its distal end shape featuring a double 45° angulation. which ensures very close contact with the CS upper wall. The device was successfully implanted in 39 out of 40 patients (97.5%). The tip electrode was eventually positioned in the distal CS in 9 patients, in the middle CS in 21 patients, and close to the ostium in the proximal CS in 9 patients. The mean acute pacing threshold voltage was 0.9 ± 0.5 V with a mean impedance of 578 ± 144 Ω as measured in unipolar distal configuration at 0.5 ms pulse width (PW). The mean A wave amplitude was 3.5 ± 2.1 mV. Early lead dislodgment occurred only once (3%) when the tip electrode was placed in the distal or middle CS, but more often (4/9 cases) when it was placed in the proximal CS. After a mean follow‐up duration of 14 ± 8.5 months, 35 of the 39 successfully implanted leads (89.7%) were still functional in terms of LA pacing and sensing. The mean chronic pacing threshold voltage was 1.5 ± 0.8 V and the mean A wave amplitude was 2.7 ± 1.6 mV. There were no lead related complications. In conclusion, the device proved to be safe and highly effective for permanent LA pacing, provided the distal tip could be positioned in the distal or middle part of the CS.