Clinical outcomes and the impact of valve morphology for transcatheter aortic valve replacement in bicuspid aortic valves: A systematic review and meta-analysis.

BACKGROUND: Bicuspid aortic valve (BAV) is present in approximately 0.5%-2% of the general population, causing significant aortic stenosis (AS) in 12%-37% of affected individuals. Transcatheter aortic valve replacement (TAVR) is being considered the treatment of choice in patients with symptomatic AS across all risk spectra. AIM: Aim Our study aims to compare TAVR outcomes in patients with BAV versus tricuspid aortic valves (TAV). METHODS: A comprehensive literature search was performed in PubMed, Web of Science, and Cochrane trials. Studies were included if they included BAV and TAV patients undergoing TAVR with quantitative data available for at least one of our predefined outcomes. Meta-analysis was performed by the random-effects model using Stata software. RESULTS: Fifty studies of 203,288 patients were included. BAV patients had increased 30-day all-cause mortality (odds ratio [OR] = 1.23 [1.00-1.50], p = 0.05), in-hospital stroke (OR = 1.39 [1.01-1.93], p = 0.05), in-hospital and 30-day PPI (OR = 1.13 [1.00-1.27], p = 0.04; OR = 1.16 [1.04-1.13], p = 0.01) and in-hospital, 30-day and 1-year aortic regurgitation (AR) (OR = 1.48 [1.19-1.83], p < 0.01; OR = 1.79 [1.26-2.52], p < 0.01; OR = 1.64 [1.03-2.60], p = 0.04). Subgroup analysis on new-generation valves showed a reduced 1-year all-cause mortality (OR = 0.86 [CI = 0.75-0.98], p = 0.03), despite higher in-hospital and 30-day PPI (OR = 0.1.21 [1.04-1.41], p = 0.01; OR = 1.17 [1.05-1.31], p = 0.01) and in-hospital AR (OR = 1.62 [1.14-2.31], p = 0.01) in the BAV group. The quality of included studies was moderate-to-high, and only three analyses presented high heterogeneity. CONCLUSION: TAVR is associated with comparable outcomes in patients with BAV and TAV. Careful selection of BAV cases by preprocedural assessment of valve anatomy and burden of calcification, pre- and post-procedural dilation, and implementing newer generations of valves may improve the safety and efficacy of TAVR in BAV patients.

Two-in-one aortic valve sizing and valvuloplasty conductance balloon catheter.

BACKGROUND: Inaccurate aortic valve sizing and selection is linked to paravalvular leakage in transcatheter aortic valve replacement (TAVR). Here, a novel sizing valvuloplasty conductance balloon (SVCB) catheter is shown to be accurate, reproducible, unbiased, and provides real-time tool for aortic valve sizing that fits within the standard valvuloplasty procedure. METHODS AND RESULTS: The SVCB catheter is a valvuloplasty device that uses real-time electrical conductance measurements based on Ohm's Law to size the balloon opposed against the aortic valve at any given inflation pressure. Accuracy and repeatability of the SVCB catheter was performed on the bench in phantoms of known dimension and ex vivo in three domestic swine aortic annuli with comparison to computed tomography (CT) and dilator measurements. Procedural workflow and safety was demonstrated in vivo in three additional domestic swine. SVCB catheter measurements had negligible bias or error for bench accuracy considered as the gold standard (Bias: -0.11 ± 0.26 mm; Error: 1.2%), but greater disagreement in ex vivo versus dilators (Bias: -0.3 ± 1.1 mm; Error: 4.5%), and ex vivo versus CT (Bias: -1.0 ± 1.6 mm; Error: 8.7%). The dilator versus CT accuracy showed similar agreement (Bias: -0.9 ± 1.5 mm; Error: 7.3%). Repeatability was excellent on the bench (Bias: 0.02 ± 0.12 mm; Error: 0.5%) and ex vivo (Bias: -0.4 ± 0.9 mm; Error: 4.6%). In animal studies, the device fit well within the procedural workflow with no adverse events or complications. CONCLUSIONS: Due to the clinical relevance of this accurate, repeatable, unbiased, and real-time sizing measurement, the SVCB catheter may provide a useful tool prior to TAVR. These findings merit a future human study.

Protease-Activated Receptor Antagonist for Reducing Cardiovascular Events - A Review on Vorapaxar.

Acute Coronary Syndrome (ACS) is a term that describes pathologies related to myocardial ischemia, and is comprised of unstable angina, non-ST elevation myocardial infarction, and ST elevation myocardial infarction. Urgent management of ACS is typically necessary to prevent future morbidity and mortality. Current medical recommendations of ACS management involve use of dual antiplatelet therapy, typically with aspirin and clopidogrel. However, newer therapies are being designed and researched to improve outcomes for patients with ACS. Vorapaxar is a novel antiplatelet therapy that inhibits thrombin-mediated platelet aggregation to prevent recurrence of ischemic events. It has been Food and Drug Administration approved for reduction of thrombotic cardiovascular events in patients with a history of MI or peripheral arterial disease with concomitant use of clopidogrel and/or aspirin, based upon the findings of the TRA 2°P-TIMI 50 trial. However, Vorapaxar was also found to have a significantly increased risk of bleeding, which must be considered when administering this drug. Based upon further subgroup analysis of both the TRA 2°P-TIMI 50 trial and TRACER trial, Vorapaxar was found to be potentially beneficial in patients with peripheral artery disease, coronary artery bypass grafting, and ischemic stroke. There are current trials in progress that are further evaluating the use of Vorapaxar in those conditions, and future research and trials are necessary to fully determine the utility of this drug.

Feasibility study of defecation studied with a wireless Fecobionics probe in normal subjects.

Several technologies have been developed for assessing anorectal function including the act of defecation. We used a new prototype of the Fecobionics technology, a multi-sensor simulated feces, to visualize defecatory patterns and introduced new metrics for anorectal physiology assessment in normal subjects. Fourteen subjects with normal fecal incontinence and constipation questionnaire scores were studied. The 10-cm-long Fecobionics device provided measurements of axial pressures, orientation, bending, and shape. The Fecobionics bag was distended to the urge-to-defecate level inside rectum where after the subjects were asked to evacuate. Physiological evacuation parameters were assessed. Special attention was paid to the Fecobionics rectoanal pressure gradient (F-RAPG) during evacuation. Anorectal manometry (ARM) and balloon expulsion test (BET) were done as references. The user interface displayed the fine coordination between pressures, orientation, bending angle, and shape. The pressures showed that Fecobionics was expelled in 11.5 s (quartiles 7.5 and 18.8s), which was shorter than the subjectively reported expulsion time of the BET balloon. Six subjects did not expel the BET balloon within 2 min. The F-RAPG was 101 (79-131) cmH2 O, whereas the ARM-RAPG was -28 (-5 to -47) cmH2 0 (p < 0.001). There was no association between the two RAPGs (r2  = 0.19). Fecobionics showed paradoxical contractions in one subject (7%) compared to 12 subjects with ARM (86%). Fecobionics obtained novel physiological data. Defecatory patterns and data are reported and can be used to guide larger-scale studies in normal subjects and patients with defecatory disorders. In accordance with other studies, this Fecobionics study questions the value of the ARM-RAPG.

Anorectal volume-pressure relations, contraction work, and flow during defecation.

Fecobionics is an integrated device that has shown promise for assessment of anorectal function. We used a wireless Fecobionics prototype to visualize defecatory patterns and to compute volume-pressure, contraction work, and flow. Twelve normal subjects were studied. The probe was 10 cm-long and contained pressure sensors and electrodes for impedance planimetry. Pressures, diameters, and volume data during defecation were analyzed. The bag was distended inside rectum to the urge-to-defecate level where after the subjects were asked to evacuate. The contraction work and defecatory flow were computed from the volume changes during expulsion. The minimum anal diameter during the evacuation was 17.6 ± 1.5 mm. The middle diameter recording was 10-20% lower than the front diameter channels and 10-20% bigger than the rear channels. The bag volume at urge correlated with the minimum diameter (r = 0.63). The diameter-pressure and volume-pressure loops were counterclockwise with phases of bag filling, isometric contraction, ejection and anal passage. The defecatory contraction work was 3520 ± 480 mL × cmH2O. The maximum flow during defecation was 302 ± 33 mL/s. The flow was associated with the anal diameter (r = 0.84) but not with the rectoanal pressure gradient (r = 0.14). Volume-pressure loops have a tremendous impact on the understanding of cardiopulmonary pathophysiology. Future studies will shed light on potential clinical impact in defecatory pathophysiology.

Effect of Genotype-Guided Oral P2Y12 Inhibitor Selection After Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

BACKGROUND: Clopidogrel is the most frequently used P2Y12 inhibitor as a component of the dual antiplatelet regimen in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Prior studies have shown the variable efficacy of clopidogrel due to genotypic differences in the CYP2C19 enzyme function, which converts clopidogrel to its active metabolite. The aim of this meta-analysis is to evaluate the effectiveness of genotype testing-guided P2Y12 inhibitor prescription therapy to patients after PCI for ACS compared to non-genotype guided conventional treatment. METHODS: A comprehensive literature search was performed in PubMed, Embase, and Cochrane to identify relevant trials. Summary effects were calculated using a DerSimonian and Laird random-effects model as odds ratio with 95% confidence intervals for all the clinical endpoints. RESULTS: Seven studies with 9617 patients were included. Genotype-guided strategy arm included prasugrel or ticagrelor prescription to patients with loss of function (LOF) of CYP219 alleles (most commonly alleles being *2 and *3) and clopidogrel prescription to those without the LOF allele. The conventional arm included patients treated with clopidogrel without genotype testing. Comparison of genotype arm with conventional arm showed decreased major adverse cardiovascular events (MACE), improved cardiovascular (CV) mortality, and reduced incidence of myocardial infarction (MI) in the genotype arm, and a similar stroke incidence in the two arms. Regarding adverse events, the incidence of stent thrombosis was lower in the genotype arm than the conventional arm. CONCLUSION: Our analysis illustrates the possible advantages of genotype-guided P2Y12 inhibitor prescription strategy compared to non-genotype-guided strategy with reductions in MACE, CV mortality, MI, and stent thrombosis. This analysis can be used as a stepping stone to conducting further trials determining the efficacy of this treatment strategy in various ACS subtypes.

Simulation of mechanical environment in active lead fixation: effect of fixation helix size.

The risk of myocardial penetration due to active-fixation screw-in type pacing leads has been reported to increase as the helix electrodes become smaller. In order to understand the contributing factors for lead penetration, we conducted finite element analyses of acute myocardial micro-damage induced by a pacemaker lead screw-in helix electrode. We compared the propensity for myocardial micro-damage of seven lead designs including a baseline model, three modified designs with various helix wire cross-sectional diameters, and three modified designs with different helix diameters. The comparisons show that electrodes with a smaller helix wire diameter cause more severe micro-damage to the myocardium in the early stage. The damage severity, represented by the volume of failed elements, is roughly the same in the middle stage, whereas in the later stage the larger helix wire diameter generally causes more severe damage. The onset of myocardial damage is not significantly affected by the helix diameter. As the helix diameter increases, however, the extent of myocardial damage increases accordingly. The present findings identified several of the major risk factors for myocardial damage whose consideration for lead use and design might improve acute and chronic lead performance.

Simulation of LV pacemaker lead in marginal vein: potential risk factors for acute dislodgement.

Although left ventricular (LV) coronary sinus lead dislodgement remains a problem, the risk factors for dislodgement have not been clearly defined. In order to identify potential risk factors for acute lead dislodgement, we conducted dynamic finite element simulations of pacemaker lead dislodgement in marginal LV vein. We considered factors such as mismatch in lead and vein diameters, velocity of myocardial motion, branch angle between the insertion vein and the coronary sinus, degree of slack, and depth of insertion. The results show that large lead-to-vein diameter mismatch, rapid myocardial motion, and superficial insertion are potential risk factors for lead dislodgement. In addition, the degree of slack presents either a positive or negative effect on dislodgement risk depending on the branch angle. The prevention of acute lead dislodgment can be enforced by inducing as much static friction force as possible at the lead-vein interface, while reducing the external force. If the latter exceeds the former, dislodgement will occur. The present findings underscore the major risk factors for lead dislodgment, which may improve implantation criterion and future lead design.

Detection of early renal transplant rejection by minimally-invasive monitoring of impedance variability.

BACKGROUND: Allograft rejection that occurs after renal transplants is identified by surveillance biopsies or by abnormal laboratory and/or hemodynamic data. The latter are insensitive markers of rejection that may not appear until significant histologic damage has already occurred. Therefore, a sensitive and specific non-invasive method of detecting early rejection of transplanted solid organs is needed. METHOD: A single canine renal allograft was implanted followed by bilateral nephrectomy. Bipolar pacing electrodes were implanted at each end of the transplanted kidney. A second set of electrodes was implanted in the liver, which served as a non-rejecting normal organ. Electrodes were connected to an implantable sensor placed in the subcutaneous tissue. Electrical tissue impedance levels were telemetrically downloaded daily. The clinical status of the transplanted organ was monitored by following the blood urea nitrogen and serum creatinine levels, urine output, and clinical appearance. After tissue impedance levels had stabilized, all immunosuppressants were abruptly discontinued. Clinical signs of rejection were then observed after a few days. RESULTS: Rejection was accompanied by changes in electrical impedance of the implanted organ. These changes, when observed, occurred 1-5 days before clinical signs of rejection appeared. CONCLUSION: Analyses of these data suggest that development of a minimally-invasive high-confidence sensor of early rejection of solid organ transplants is feasible.

Bi-ventricular pacing improves pump function only with adequate myocardial perfusion in canine hearts with pseudo-left bundle branch block.

Bi-ventricular (BiV) pacing is an effective therapy for the treatment of cardiac electromechanical (EM) dysfunction. The reason(s), however, for therapy non-response in approximately one-third of the subjects remains unclear, especially as it relates to myocardial perfusion and pacing location. In this study, we examined how acute BiV pacing response may be related to underlying myocardial perfusion coupled with pacing near or distant to the area of perfusion. In 10 open-chest anesthetized canines, coronary blood flow to the left ventricular (LV) anterior wall (AW: n = 5) and lateral wall (LW: n = 5) was controlled during four pacing conditions: right atrial, right ventricular (pseudo-left bundle branch block; [pseudo-LBBB]), BiV-LW and BiV-AW. Local EM function (piezo-electrical crystals and electrodes), along with global hemodynamic parameters, were measured during all pacing conditions at three coronary perfusion rates (≥0.40 mL/min/g, 0.20-0.40 mL/min/g and <0.20 mL/min/g). A positive BiV therapy response was assessed by a significant increase in the maximum cardiac output compared with the pseudo-LBBB condition. Despite no improvement in QRS duration, BiV-LW pacing improved LV function compared with the pseudo-LBBB pacing condition (P value <0.01). This improvement with BiV-LW pacing was seen above a certain myocardial perfusion threshold and was independent of any increases in regional coronary blood flow with BiV pacing. At lower myocardial perfusion rates, LV function was not improved with BiV pacing at any location. This study underscores the significance of even mild ischemia on BiV pacing response.

Potential of gallium-based leads for cardiac rhythm management devices.

We propose the use of gallium (Ga), a metal that is liquid at physiological temperatures, or one of its alloys, for use as the conducting material in the leads of implantable pacemakers or cardioverter defibrillators. It is proposed that a liquid conductor will make these leads more pliable and thus less susceptible to fracture in situ. As an initial step towards utilizing liquid gallium in leads, the biocompatibility of Ga was investigated via cytotoxicity, hemocompatibility, and intracutaneous injection testing. Unipolar pacing Ga prototypes were fabricated by adapting existing pacemaker leads. The electrical impedance and pulse transmission ability of these leads were examined. Ga was well tolerated both in vitro and in vivo. Additionally, the Ga prototypes conductors behaved as low magnitude resistances that did not distort pulses as generated by conventional pacemakers. These results indicate that Ga is an appropriate material for implantable cardiac stimulators and will be a focus of our liquid metal prototypes.

Large mycotic pseudoaneurysm of the left circumflex treated with antibiotics and covered stent.

Coronary artery mycotic aneurysms are rare complications of infective endocarditis. They are usually managed surgically with excision of the aneurysm. This surgical procedure has high morbidity and mortality. We report a case of a giant mycotic coronary aneurysm following infective endocarditis which was treated with intravenous antibiotics and covered stent. This case highlights a new treatment modality in critically ill patients.

Chronotropic incompetence in patients with an implantable cardioverter defibrillator: prevalence and predicting factors.

Chronotropic incompetence (CI), which has not been systematically examined in the ICD patient population, may have implications for device programming. A total of 123 ICD patients were classified into three groups: single-chamber ICD with sinus rhythm, dual-chamber ICD with sinus rhythm, and single-chamber ICD with permanent atrial fibrillation. Heart rate response, maximum oxygen uptake, and oxygen uptake at the anaerobic threshold were measured during treadmill exercise testing. In addition, clinical variables such as antiarrhythmic drug therapy, underlying heart disease, and left-ventricular (LV) ejection fraction were recorded. Of the patients studied, 38% were chronotropically incompetent (47/123). Significant predictors of CI were as follows: presence of a coronary disease (P = 0.036), prior cardiac surgery (P = 0.037), chronic drug therapy with beta-blockers (P = 0.032), administration of amiodarone (P = 0.025), and a combination of these two forms of treatment (P = 0.01). Spiroergometry revealed reduced exercise capacity (P = 0.041) and lessened VO2max (P = 0.034) among chronotropically incompetent patients. A large percentage of ICD patients demonstrates CI with subsequently reduced physical stress tolerance. In light of the DAVID study, we believe that a closer examination of rate-adaptive modes for ICD patients is warranted under enhanced conditions: (1) optimized AV interval programming; (2) utilization of new algorithms to reduce ventricular pacing in combination with rate-adaptive atrial pacing, with the goal of addressing CI while minimizing ventricular pacing; and (3) an optimized upper heart-rate limit.