Transcatheter aortic valve implantation using the SAPIEN 3 valve to treat aortic regurgitation: The French multicentre S3AR study.

BACKGROUND: Transcatheter aortic valve implantation now has a major role in the treatment of patients with severe aortic stenosis. However, evidence is scarce on its feasibility and safety to treat patients with pure aortic regurgitation. AIMS: We sought to evaluate the results of transcatheter aortic valve implantation using the balloon-expandable SAPIEN 3 transcatheter heart valve (Edwards Lifesciences, Irvine, CA, USA) in patients with pure aortic regurgitation on native non-calcified valves. METHODS: We conducted a retrospective and prospective French multicentre observational study. We included all patients with symptomatic severe pure aortic regurgitation on native non-calcified valves, contraindicated to or at high risk for surgical valve replacement, who underwent transcatheter aortic valve implantation using the SAPIEN 3 transcatheter heart valve. RESULTS: A total of 37 patients (male sex, 73%) with a median age of 81years (interquartile range 69-85years) were screened using transthoracic echocardiography and computed tomography and were included at eight French centres. At baseline, 83.8% of patients (n=31) had dyspnoea New York Heart Association class≥III. The device success rate was 94.6% (n=35). At 30days, the all-cause mortality rate was 8.1% (n=3) and valve migration occurred in 10.8% of cases (n=4). Dyspnoea New York Heart Association class≤II was seen in 86.5% of patients (n=32), and all survivors had aortic regurgitation grade≤1. At 1-year follow-up, all-cause mortality was 16.2% (n=6), 89.7% (n=26/29) of survivors were in New York Heart Association class≤II and all had aortic regurgitation grade≤2. CONCLUSION: Transcatheter aortic valve implantation using the SAPIEN 3 transcatheter heart valve seems promising to treat selected high-risk patients with pure aortic regurgitation on non-calcified native valves, contraindicated to surgical aortic valve replacement.

Left Ventricular Rapid Pacing Via the Valve Delivery Guidewire in Transcatheter Aortic Valve Replacement.

OBJECTIVES: This study investigated whether left ventricular (LV) stimulation via a guidewire-reduced procedure duration while maintaining efficacy and safety compared with standard right ventricular (RV) stimulation. BACKGROUND: Rapid ventricular pacing is necessary to ensure cardiac standstill during transcatheter aortic valve replacement (TAVR). METHODS: This is a prospective, multicenter, single-blinded, superiority, randomized controlled trial. Patients undergoing transfemoral TAVR with a SAPIEN valve (Edwards Lifesciences, Irvine, California) were allocated to LV or RV stimulation. The primary endpoint was procedure duration. Secondary endpoints included efficacy, safety, and cost at 30 days. RESULTS: Between May 2017 and May 2018, 307 patients were randomized, but 4 were excluded because they did not receive the intended treatment: 303 patients were analyzed in the LV (n = 151) or RV (n = 152) stimulation groups. Mean procedure duration was significantly shorter in the LV stimulation group (48.4 ± 16.9 min vs. 55.6 ± 26.9 min; p = 0.0013), with a difference of -0.12 (95% confidence interval: -0.20 to -0.05) in the log-transformed procedure duration (p = 0.0012). Effective stimulation was similar in the LV and RV stimulation groups: 124 (84.9%) versus 128 (87.1%) (p = 0.60). Safety of stimulation was also similar in the LV and RV stimulation groups: procedural success occurred in 151 (100%) versus 151 (99.3%) patients (p = 0.99); 30-day MACE-TAVR (major adverse cardiovascular event-transcatheter aortic valve replacement) occurred in 21 (13.9%) versus 26 (17.1%) patients (p = 0.44); fluoroscopy time (min) was lower in the LV stimulation group (13.48 ± 5.98 vs. 14.60 ± 5.59; p = 0.02), as was cost (€18,807 ± 1,318 vs. €19,437 ± 2,318; p = 0.001). CONCLUSIONS: Compared with RV stimulation, LV stimulation during TAVR was associated with significantly reduced procedure duration, fluoroscopy time, and cost, with similar efficacy and safety. (Direct Left Ventricular Rapid Pacing Via the Valve Delivery Guide-wire in TAVR [EASY TAVI]; NCT02781896).

Rapid pacing using the left ventricular guidewire: Reviving an old technique to simplify BAV and TAVI procedures.

OBJECTIVES: We sought to demonstrate the safety and efficacy of rapid left ventricular (LV) pacing through the guidewire during balloon aortic valvuloplasty (BAV) and Transaortic valve implantation (TAVI). BACKGROUND: Right ventricular temporary pacing during TAVI and BAV is time-consuming and associated with vascular and pericardial complications. METHODS: Rapid left ventricular pacing was provided via the back-up 0.035″ guidewire. The cathode of an external pacemaker was placed on the tip of the 0.035″ wire and the anode on a needle inserted into the groin. Insulation was ensured by the balloon or TAVI catheter. RESULTS: 38 BAV and 87 TAVI procedures were performed in 113 consecutive patients in three centers with one for one pacing (160-200 bpm) in all patients. A significant reduction in blood pressure was achieved with a mean systolic pressure of 44 mm Hg during stimulation. Mean procedural time was 49.7 ± 31 min for BAV and 68.7 ± 30.9 for TAVI. A temporary venous pacemaker was required in 12 patients; only 12% of TAVI patients had a femoral central venous catheter. Femoral venous puncture was not performed in BAV patients. No venous vascular complications were observed. One case of successfully treated tamponade (0.8%) occurred 8 hr post procedure. In-hospital mortality rates were 4.6% and 2.6% in the TAVI and BAV groups, respectively. CONCLUSIONS: Use of the LV guidewire for rapid pacing during BAV and TAVI was shown to be simple, reproducible, and prevented complications associated with RV temporary leads thus potentially simplifying TAVI and enhancing its safety. © 2016 Wiley Periodicals, Inc.

Cyclosporine before PCI in Patients with Acute Myocardial Infarction.

BACKGROUND: Experimental and clinical evidence suggests that cyclosporine may attenuate reperfusion injury and reduce myocardial infarct size. We aimed to test whether cyclosporine would improve clinical outcomes and prevent adverse left ventricular remodeling. METHODS: In a multicenter, double-blind, randomized trial, we assigned 970 patients with an acute anterior ST-segment elevation myocardial infarction (STEMI) who were undergoing percutaneous coronary intervention (PCI) within 12 hours after symptom onset and who had complete occlusion of the culprit coronary artery to receive a bolus injection of cyclosporine (administered intravenously at a dose of 2.5 mg per kilogram of body weight) or matching placebo before coronary recanalization. The primary outcome was a composite of death from any cause, worsening of heart failure during the initial hospitalization, rehospitalization for heart failure, or adverse left ventricular remodeling at 1 year. Adverse left ventricular remodeling was defined as an increase of 15% or more in the left ventricular end-diastolic volume. RESULTS: A total of 395 patients in the cyclosporine group and 396 in the placebo group received the assigned study drug and had data that could be evaluated for the primary outcome at 1 year. The rate of the primary outcome was 59.0% in the cyclosporine group and 58.1% in the control group (odds ratio, 1.04; 95% confidence interval [CI], 0.78 to 1.39; P=0.77). Cyclosporine did not reduce the incidence of the separate clinical components of the primary outcome or other events, including recurrent infarction, unstable angina, and stroke. No significant difference in the safety profile was observed between the two treatment groups. CONCLUSIONS: In patients with anterior STEMI who had been referred for primary PCI, intravenous cyclosporine did not result in better clinical outcomes than those with placebo and did not prevent adverse left ventricular remodeling at 1 year. (Funded by the French Ministry of Health and NeuroVive Pharmaceutical; CIRCUS ClinicalTrials.gov number, NCT01502774; EudraCT number, 2009-013713-99.).

Rationale and design of the Cyclosporine to ImpRove Clinical oUtcome in ST-elevation myocardial infarction patients (the CIRCUS trial).

BACKGROUND: Both acute myocardial ischemia and reperfusion contribute to cardiomyocyte death in ST-elevation myocardial infarction (STEMI). The final infarct size is the principal determinant of subsequent clinical outcome in STEMI patients. In a proof-of-concept phase II trial, the administration of cyclosporine prior to primary percutaneous coronary intervention (PPCI) has been associated with a reduction of infarct size in STEMI patients. METHODS: CIRCUS is an international, prospective, multicenter, randomized, double-blinded, placebo-controlled trial. The study is designed to compare the efficacy and safety of cyclosporine versus placebo, in addition to revascularization by PPCI, in patients presenting with acute anterior myocardial infarction within 12 hours of symptoms onset and initial TIMI flow ≤1 in the culprit left anterior descending coronary artery. Patients are randomized in a 1:1 fashion to 2.5 mg/kg intravenous infusion of cyclosporine or matching placebo performed in the minutes preceding PCI. The primary efficacy end point of CIRCUS is a composite of 1-year all-cause mortality, rehospitalization for heart failure or heart failure worsening during initial hospitalization, and left ventricular adverse remodeling as determined by sequential transthoracic echochardiography. Secondary outcomes will be tested using a hierarchical sequence of left ventricular (LV) ejection fraction and absolute measurements of LV volumes. The composite of death and rehospitalization for heart failure or heart failure worsening during initial hospitalization will be further assessed at three years after the initial infarction. RESULTS: Recruitment lasted from April 2011 to February 2014. The CIRCUS trial has recruited 975 patients with acute anterior myocardial infarction. The 12-months results are expected to be available in 2015. CONCLUSIONS: The CIRCUS trial is testing the hypothesis that cyclosporine in addition to early revascularization with PPCI compared to placebo in patients with acute anterior myocardial infarction reduces the incidence of death, heart failure and adverse LV remodeling at one-year follow-up.

Effect of cyclosporine on reperfusion injury in acute myocardial infarction.

BACKGROUND: Experimental evidence suggests that cyclosporine, which inhibits the opening of mitochondrial permeability-transition pores, attenuates lethal myocardial injury that occurs at the time of reperfusion. In this pilot trial, we sought to determine whether the administration of cyclosporine at the time of percutaneous coronary intervention (PCI) would limit the size of the infarct during acute myocardial infarction. METHODS: We randomly assigned 58 patients who presented with acute ST-elevation myocardial infarction to receive either an intravenous bolus of 2.5 mg of cyclosporine per kilogram of body weight (cyclosporine group) or normal saline (control group) immediately before undergoing PCI. Infarct size was assessed in all patients by measuring the release of creatine kinase and troponin I and in a subgroup of 27 patients by performing magnetic resonance imaging (MRI) on day 5 after infarction. RESULTS: The cyclosporine and control groups were similar with respect to ischemia time, the size of the area at risk, and the ejection fraction before PCI. The release of creatine kinase was significantly reduced in the cyclosporine group as compared with the control group (P=0.04). The release of troponin I was not significantly reduced (P=0.15). On day 5, the absolute mass of the area of hyperenhancement (i.e., infarcted tissue) on MRI was significantly reduced in the cyclosporine group as compared with the control group, with a median of 37 g (interquartile range, 21 to 51) versus 46 g (interquartile range, 20 to 65; P=0.04). No adverse effects of cyclosporine administration were detected. CONCLUSIONS: In our small, pilot trial, administration of cyclosporine at the time of reperfusion was associated with a smaller infarct by some measures than that seen with placebo. These data are preliminary and require confirmation in a larger clinical trial.

Assessment of acute myocardial infarction using MDCT after percutaneous coronary intervention: comparison with MRI.

OBJECTIVE: Imaging to determine myocardial infarct size is difficult in the emergency setting because the current gold standards, MRI and nuclear medicine techniques, are difficult to perform in unstable patients. Delayed enhanced MDCT has recently been proposed as a technique to study contrast uptake in infarcted myocardium. In this study, we compared the extent of acute myocardial infarction as measured by delayed enhanced MDCT performed immediately after percutaneous coronary intervention (PCI) without an additional iodine injection with that measured by delayed gadolinium-enhanced MRI. SUBJECTS AND METHODS: Nineteen consecutive patients presenting with primary acute myocardial infarction underwent delayed enhanced MDCT immediately after coronary angioplasty and underwent delayed enhanced MRI within 8 days of angioplasty. Only patients with a thrombolysis in myocardial infarction (TIMI) score of 0 or 1 of the culprit coronary artery before endovascular angioplasty and TIMI score of 2 or 3 after angioplasty were selected. Comparison of delayed enhanced MDCT and delayed enhanced MRI was performed by three observers and focused on identifying the involved segments and determining the transmural extent of enhancement and infarct size. RESULTS: The mean signal intensity was significantly higher in the involved territory than in healthy myocardium: 197 +/- 81 H versus 71 +/- 20 H, respectively (p < 0.0001). We found significant agreement between delayed enhanced MDCT and delayed enhanced MRI for the number of involved segments, transmural extent of enhancement, and infarct size (r(2) = 0.74, 0.76, and 0.67, respectively; p < 0.0001) with good interobserver reproducibility (kappa = 0.8). CONCLUSION: The results of our study show that delayed enhanced MDCT allows accurate visualization of early myocardial contrast uptake compared with delayed enhanced MRI and does not require an additional contrast injection after PCI.

Acute chest pain with normal coronary angiogram: role of contrast-enhanced multidetector computed tomography in the differential diagnosis between myocarditis and myocardial infarction.

OBJECTIVE: To evaluate the accuracy of delayed-enhanced multidetector computed tomography (MSCT) for differentiating between myocarditis and myocardial infarction in patients with normal x-ray coronary angiography. METHODS: Twelve consecutive patients referred for acute chest pain and normal coronary arteries on x-ray coronary angiography were involved in this study. Delayed-enhanced MSCT and postgadolinium delayed-enhanced magnetic resonance imaging (MRI) examinations were performed within 36 hours and 4 days, respectively, after patient admission. Comparison between delayed-enhanced MSCT and MRI was performed by 3 independent blinded observers in term of final diagnosis, number of involved segments, and transmural extent. RESULTS: Final diagnosis between myocarditis and myocardial infarction was identical for delayed-enhanced MSCT and MRI with a significant agreement for number of involved segments and transmural extension. Interobserver reproducibility was good for both techniques. CONCLUSIONS: We demonstrated that delayed-enhanced MSCT allows differentiation between myocardial infarction and myocarditis with the same accuracy at acute phase compared with MRI.

Long-term benefit of postconditioning.

BACKGROUND: We previously demonstrated that ischemic postconditioning decreases creatine kinase release, a surrogate marker for infarct size, in patients with acute myocardial infarction. Our objective was to determine whether ischemic postconditioning could afford (1) a persistent infarct size limitation and (2) an improved recovery of myocardial contractile function several months after infarction. METHODS AND RESULTS: Patients presenting within 6 hours of the onset of chest pain, with suspicion for a first ST-segment-elevation myocardial infarction, and for whom the clinical decision was made to treat with percutaneous coronary intervention, were eligible for enrollment. After reperfusion by direct stenting, 38 patients were randomly assigned to a control (no intervention; n=21) or postconditioned group (repeated inflation and deflation of the angioplasty balloon; n=17). Infarct size was assessed both by cardiac enzyme release during early reperfusion and by 201thallium single photon emission computed tomography at 6 months after acute myocardial infarction. At 1 year, global and regional contractile function was evaluated by echocardiography. At 6 months after acute myocardial infarction, single photon emission computed tomography rest-redistribution index (a surrogate for infarct size) averaged 11.8+/-10.3% versus 19.5+/-13.3% in the postconditioned versus control group (P=0.04), in agreement with the significant reduction in creatine kinase and troponin I release observed in the postconditioned versus control group (-40% and -47%, respectively). At 1 year, the postconditioned group exhibited a 7% increase in left ventricular ejection fraction compared with control (P=0.04). CONCLUSIONS: Postconditioning affords persistent infarct size reduction and improves long-term functional recovery in patients with acute myocardial infarction.

Postconditioning the human heart.

BACKGROUND: In animal models, brief periods of ischemia performed just at the time of reperfusion can reduce infarct size, a phenomenon called postconditioning. In this prospective, randomized, controlled, multicenter study, we investigated whether postconditioning may protect the human heart during coronary angioplasty for acute myocardial infarction. METHODS AND RESULTS: Thirty patients, submitted to coronary angioplasty for ongoing acute myocardial infarction, contributed to the study. Patients were randomly assigned to either a control or a postconditioning group. After reperfusion by direct stenting, control subjects underwent no further intervention, whereas postconditioning was performed within 1 minute of reflow by 4 episodes of 1-minute inflation and 1-minute deflation of the angioplasty balloon. Infarct size was assessed by measuring total creatine kinase release over 72 hours. Area at risk and collateral blood flow were estimated on left ventricular and coronary angiograms. No adverse events occurred in the postconditioning group. Determinants of infarct size, including ischemia time, size of the area at risk, and collateral flow, were comparable between the 2 groups. Area under the curve of creatine kinase release was significantly reduced in the postconditioning compared with the control group, averaging 208 984+/-26 576 compared with 326,095+/-48,779 (arbitrary units) in control subjects, ie, a 36% reduction in infarct size. Blush grade, a marker of myocardial reperfusion, was significantly increased in postconditioned compared with control subjects: 2.44+/-0.17 versus 1.95+/-0.27, respectively (P<0.05). CONCLUSIONS: This study suggests that postconditioning by coronary angioplasty protects the human heart during acute myocardial infarction.

150 microgram intracoronary adenosine bolus for accurate fractional flow reserve assessment of angiographically intermediate coronary stenosis.

AIMS: Fractional flow reserve measurement is based upon achieving maximum hyperemia. A 40 microg intracoronary (IC) adenosine bolus sometimes seems insufficient, and we therefore sought to assess the possible role of 100-150 microg boli in routine. METHODS AND RESULTS: 108 intermediate (49+/-16%) stenoses were consecutively studied with 6F catheters. A history of myocardial infarction in the territory of the explored artery or myocardial hypertrophy were the exclusion criteria. Mean FFR was 0.82+/-0.12 with a 40 microg adenosine bolus and decreased to 0.80+/-0.12 and 0.80+/-13 respectively with 100microg and 150 microg boli (P<0.001 vs 40microg in both cases; 100 vs 150 microg, NS). The 40 microg bolus failed to diagnose 8 out of 30 (27%) significant stenoses (i.e., final FFR <0.75). The large boli led to 12 (11%) transient asymptomatic and spontaneously resolving AV blocks without other side-effects. CONCLUSION: FFR underestimated a quarter of intermediate stenoses with the currently used 40microg IC adenosine bolus. A large bolus up to 150 microg appears to be accurate and safe for routine FFR measurement.

Ginkgo biloba extract EGb 761 attenuates myocardial stunning in the pig heart.

Myocardial stunning, a transient contractile dysfunction that appears following a brief period of ischemia, is at least partly due to the production of oxygen-derived free radicals. The objective of the present study was to determine whether the Ginkgo biloba extract EGb761, which has antioxidant properties in vitro, can attenuate myocardial stunning in vivo. Forty-seven anesthetized open-chest farm pigs underwent 10 min of occlusion of the left anterior descending coronary artery (LAD), followed by 3 hours of reperfusion. They were pretreated with either physiological saline, 100 mg or 300 mg of EGb 761 (Protocol I) or 3 mg or 9 mg of ginkgolide B (GkB) (Protocol II). Contractile function was assessed by sonomicrometry. Both doses of EGb 761 significantly improved recovery of contractile function in the reperfused myocardium with segment shortening averaging 23 +/- 5 % of baseline values at 3 hours post-reflow in controls versus 81 +/- 10 % and 57 +/- 12 % in the EGb100 and EGb300 groups, respectively (p < 0.05 vs control in both cases). In contrast, neither dose of GkB improved functional recovery during reperfusion. ESR experiments revealed that EGb761 resulted in a 59 % decrease in myocardial spin-adduct release during reperfusion (p < 0.05 versus control and GkB groups). A significant 28 % decrease (p < 0.05 vs control group) was also obtained in GkB-treated animals. These results indicate that EGb 761 can attenuate myocardial stunning following a brief ischemic insult in the in situ pig heart by an effect that involves a decrease in the formation of free radicals. As the effect of EGb 761 on functional recovery cannot be explained by the presence of GkB, the beneficial action of the extract on myocardial stunning likely involves complementary effects of both its non-ginkgolide and ginkgolide constituents.