A "fully upper extremity" bailout of direct transaxillary large bore arterial access: A refinement within arm's reach?

Contemporary direct ("fully percutaneous") transaxillary (TAx) large-bore arterial access technique advocates for a 0.018" wire to be passed from femoral arterial access to axillary artery to serve percutaneous bailout options. However, in certain patients, avoiding femoral arterial access entirely may be desired. We describe the merits of a "fully upper extremity" (FUE) bailout approach, as a refinement to previously described direct TAx technique.

Refractory Pulmonary Edema and Upper Body Hypoxemia During Veno-Arterial Extracorporeal Membrane Oxygenation-A Case for Atrial Septostomy.

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) provides mechanical circulatory support for patients with advanced cardiogenic shock, facilitating myocardial recovery and limiting multi-organ failure. In patients with severely limited left ventricular ejection, peripheral VA-ECMO can further increase left ventricular and left atrial pressures (LAP). Failure to decompress the left heart under these circumstances can result in pulmonary edema and upper body hypoxemia, that is, myocardial and cerebral ischemia. Atrial septostomy can decrease LAP in these situations. However, the effects of atrial septostomy on upper body oxygenation remain unknown. After IRB approval, we identified 9 out of 242 adult VA-ECMO patients between January 2011 and June 2016 who also underwent atrial septostomy for refractory pulmonary edema/upper body hypoxemia. We analyzed LAP/pulmonary capillary wedge pressure (PCWP), right atrial pressures (RAPs), Pa O2 /Fi O2 ratios (blood samples from right radial artery), intrathoracic volume status, and resolution of pulmonary edema before and up to 48 h after septostomy. There were no procedure-related complications. Thirty-day survival was 44%. LAP/PCWP decreased by approximately 40% immediately following septostomy and remained so for at least 24 h. Pa O2 /Fi O2 ratios significantly increased from 0.49 (0.38-2.12) before to 5.35 (3.01-7.69) immediately after septostomy and continued so for 24 h, 6.6 (4.49-10.93). Radiographic measurements also indicated a significant improvement in thoracic intravascular volume status after atrial septostomy. Atrial septostomy reduces LAP and improves upper body oxygenation and intrathoracic vascular volume status in patients developing severe refractory pulmonary edema while undergoing peripheral VA-ECMO. Atrial septostomy therefore appears safe and suitable to reduce the risk of upper body ischemia under these circumstances.

Understanding Treatment Preferences for Patients with Tricuspid Regurgitation.

Background. Tricuspid regurgitation (TR) is a high-prevalence disease associated with poor quality of life and mortality. This quantitative patient preference study aims to identify TR patients' perspectives on risk-benefit tradeoffs. Methods. A discrete-choice experiment was developed to explore TR treatment risk-benefit tradeoffs. Attributes (levels) tested were treatment (procedure, medical management), reintervention risk (0%, 1%, 5%, 10%), medications over 2 y (none, reduce, same, increase), shortness of breath (none/mild, moderate, severe), and swelling (never, 3× per week, daily). A mixed logit regression model estimated preferences and calculated predicted probabilities. Relative attribute importance was calculated. Subgroup analyses were performed. Results. An online survey was completed by 150 TR patients. Shortness of breath was the most important attribute and accounted for 65.8% of treatment decision making. The average patients' predicted probability of preferring a "procedure-like" profile over a "medical management-like" profile was 99.7%. This decreased to 78.9% for a level change from severe to moderate in shortness of breath in the "medical management-like" profile. Subgroup analysis confirmed that patients older than 64 y had a stronger preference to avoid severe shortness of breath compared with younger patients (P < 0.02), as did severe or worse TR patients relative to moderate. New York Heart Association class I/II patients more strongly preferred to avoid procedural reintervention risk relative to class III/IV patients (P < 0.03). Conclusion. TR patients are willing to accept higher procedural reintervention risk if shortness of breath is alleviated. This risk tolerance is higher for older and more symptomatic patients. These results emphasize the appropriateness of developing TR therapies and the importance of addressing symptom burden. Highlights: This study provides quantitative patient preference data from clinically confirmed tricuspid regurgitation (TR) patients to understand their treatment preferences.Using a targeted literature search and patient, physician, and Food and Drug Administration feedback, a cross-sectional survey with a discrete-choice experiment that focused on 5 of the most important attributes to TR patients was developed and administered online.TR patients are willing to accept higher procedural reintervention risk if shortness of breath is alleviated, and this risk tolerance is higher for older and more symptomatic patients.

Commensal Streptococcal Infective Endocarditis of the Native Mitral Valve in a Transcatheter Aortic Valve Replacement (TAVR) Patient: A Heartful, a Handful, and a Mouthful.

An 88-year-old woman with an extensive medical history presented to the hospital with altered mental status, vague abdominal pain, and dysuria. A previous transcatheter aortic valve replacement (TAVR) prosthesis was known to be failing and was suspected to have acquired a vegetation. No other infective endocarditis (IE) stigmata were present. Fortunately, the work-up for replacement was allowed to proceed with a broader cardiac examination from which a mitral vegetation was identified and IE then treated.

Enhanced Left Ventricular Recovery in Treatment of Mitral Regurgitation With Severe Left Ventricular Dysfunction.

A 73-year-old male patient presented with shortness of breath at rest resulting from new-onset severe primary mitral regurgitation with a flail posterior leaflet, left ventricular dysfunction, and cardiogenic shock. After initial stabilization in the intensive care unit, multiple treatment options were considered for this patient, all associated with significant mortality. Ultimately, operative mitral valve repair with Impella 5.5 placement was performed for postoperative hemodynamic support. Surgical repair provided elimination of mitral regurgitation. Impella support was maintained for 7 days to provide unloading of the left ventricle. After device removal, the patient had sustained left ventricular recovery with significantly improved ejection fraction. Full left ventricular support and unloading may decrease operative risk and promote left ventricular recovery in patients with severe mitral regurgitation and left ventricular dysfunction. This case emphasizes the value of ventricular unloading to facilitate the recovery of left ventricular function as a treatment option for patients with challenging cases of severe mitral regurgitation and left ventricular dysfunction.

Push Is Better Than Shove: Radial Snare-Guided Repositioning of an Extracardiac Impella Device.

BACKGROUND: Bedside manipulation of an Impella CP is often necessary as subtle changes in device position after initial placement can dramatically affect proper function. CASE PRESENTATION: A 59 year old man in cardiogenic shock on V-A ECMO support underwent Impella CP placement to function as an LV vent. Bedside manipulation led to the Impella dislodging into the ascending aorta and kinking in half. Percutaneous rescue was performed in the cardiac catheterization laboratory by snaring the device, and guiding it back into the LV in a controlled fashion restoring normal function. CONCLUSIONS: Bedside manipulation of an Impella is often necessary, but may cause device dislodgement. Re-entry into the LV is challenging and replacement of the device carries significant cost and clinical implications. Radial approach, snare guided repositioning offers an alternative solution to an increasingly encountered challenge.

PDGF-induced vascular smooth muscle cell proliferation is associated with dysregulation of insulin receptor substrates.

In vascular smooth muscle cells (VSMCs), platelet-derived growth factor (PDGF) plays a major role in inducing phenotypic switching from contractile to proliferative state. Importantly, VSMC phenotypic switching is also determined by the phosphorylation state/expression levels of insulin receptor substrate (IRS), an intermediary signaling component that is shared by insulin and IGF-I. To date, the roles of PDGF-induced key proliferative signaling components including Akt, p70S6kinase, and ERK1/2 on the serine phosphorylation/expression of IRS-1 and IRS-2 isoforms remain unclear in VSMCs. We hypothesize that PDGF-induced VSMC proliferation is associated with dysregulation of insulin receptor substrates. Using human aortic VSMCs, we demonstrate that prolonged PDGF treatment led to sustained increases in the phosphorylation of protein kinases such as Akt, p70S6kinase, and ERK1/2, which mediate VSMC proliferation. In addition, PDGF enhanced IRS-1/IRS-2 serine phosphorylation and downregulated IRS-2 expression in a time- and concentration-dependent manner. Notably, phosphoinositide 3-kinase (PI 3-kinase) inhibitor (PI-103) and mammalian target of rapamycin inhibitor (rapamycin), which abolished PDGF-induced Akt and p70S6kinase phosphorylation, respectively, blocked PDGF-induced IRS-1 serine phosphorylation and IRS-2 downregulation. In contrast, MEK1/ERK inhibitor (U0126) failed to block PDGF-induced IRS-1 serine phosphorylation and IRS-2 downregulation. PDGF-induced IRS-2 downregulation was prevented by lactacystin, an inhibitor of proteasomal degradation. Functionally, PDGF-mediated IRS-1/IRS-2 dysregulation resulted in the attenuation of insulin-induced IRS-1/IRS-2-associated PI 3-kinase activity. Pharmacological inhibition of PDGF receptor tyrosine kinase with imatinib prevented IRS-1/IRS-2 dysregulation and restored insulin receptor signaling. In conclusion, strategies to inhibit PDGF receptors would not only inhibit neointimal growth but may provide new therapeutic options to prevent dysregulated insulin receptor signaling in VSMCs in nondiabetic and diabetic states.

Transthoracic Doppler echocardiography to noninvasively assess coronary vasoconstrictor and dilator responses in humans.

Human studies of coronary circulation are limited because of methodological issues. Recently, a noninvasive transthoracic duplex ultrasound (TTD) technique has emerged as an important tool to measure coronary blood flow velocity (CBV) in conscious humans. We employed two protocols to determine whether noninvasive "native" coronary artery velocity responses to constrictor or dilator stimuli assessed by TTD provide reliable data. In the first protocol, coronary vascular resistance (CVR = diastolic blood pressure/CBV) responses to static handgrip were examined in the left internal mammary artery (LIMA) and native left anterior descending artery (LAD) into which the graft was inserted (patient age 63 +/- 3 years). Our prior report documented increased CVR in the LIMA graft during static handgrip (Momen et al., J Appl Physiol 102: 735-739, 2007). We hypothesized that the magnitude of increases in CVR during handgrip would be similar in the LIMA graft and LAD in the same individual. Percent increases in CVR were similar in the LIMA and distal native LAD (27 +/- 4% vs. 28 +/- 6%). In the second protocol, we studied six patients (age 61 +/- 3 years) who underwent cardiac catheterization of the LAD. We compared coronary vasodilator responses to intravenous adenosine infusion (0.14 mg.kg(-1).min(-1)) obtained by intracoronary Doppler guidewire technique and TTD on separate studies. The relative increases in CBV with adenosine obtained by intracoronary Doppler guidewire and TTD were similar (62 +/- 10% vs. 65 +/- 12%). Noninvasive TTD provides reliable human coronary circulatory constrictor and dilator data.

Pivotal Clinical Study to Evaluate the Safety and Effectiveness of the MANTA Percutaneous Vascular Closure Device.

BACKGROUND: Open surgical closure and small-bore suture-based preclosure devices have limitations when used for transcatheter aortic valve replacement, percutaneous endovascular abdominal aortic aneurysm repair, or percutaneous thoracic endovascular aortic aneurysm repair. The MANTA vascular closure device is a novel collagen-based technology designed to close large bore arteriotomies created by devices with an outer diameter ranging from 12F to 25F. In this study, we determined the safety and effectiveness of the MANTA vascular closure device. METHODS AND RESULTS: A prospective, single arm, multicenter investigation in patients undergoing transcatheter aortic valve replacement, percutaneous endovascular abdominal aortic aneurysm repair, or thoracic endovascular aortic aneurysm repair at 20 sites in North America. The primary outcome was time to hemostasis. The primary safety outcomes were accessed site-related vascular injury or bleeding complications. A total of 341 patients, 78 roll-in, and 263 in the primary analysis cohort, were entered in the study between November 2016 and September 2017. For the primary analysis cohort, transcatheter aortic valve replacement was performed in 210 (79.8%), and percutaneous endovascular abdominal aortic aneurysm repair or thoracic endovascular aortic aneurysm repair was performed in 53 (20.2%). The 14F MANTA was used in 42 cases (16%), and the 18F was used in 221 cases(84%). The mean effective sheath outer diameter was 22F (7.3 mm). The mean time to hemostasis was 65±157 seconds with a median time to hemostasis of 24 seconds. Technical success was achieved in 257 (97.7%) patients, and a single device was deployed in 262 (99.6%) of cases. Valve Academic Research Consortium-2 major vascular complications occurred in 11 (4.2%) cases: 4 received a covered stent (1.5%), 3 had access site bleeding (1.1%), 2 underwent surgical repair (0.8%), and 2 underwent balloon inflation (0.8%). CONCLUSIONS: In a selected population, this study demonstrated that the MANTA percutaneous vascular closure device can safely and effectively close large bore arteriotomies created by current generation transcatheter aortic valve replacement, percutaneous endovascular abdominal aortic aneurysm repair, and thoracic endovascular aortic aneurysm repair devices. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02908880.

C(6)-Ceramide-Coated Catheters Promote Re-Endothelialization of Stretch-Injured Arteries.

OBJECTIVE: Drug eluting stents have recently been associated with the increased risk of adverse thrombogenic events and/or late luminal loss, which is highly associated with incomplete re-endothelialization. The increased risks behoove the design of alternative delivery modalities and/or drugs that do not compromise the re-endotheliaization process. The objective of the present study is to elucidate the biological mechanism(s) by which non-stent-based delivery modalities for the anti-proliferative lipid metabolite, C(6)-ceramide, could lead to a reduction in arterial injury after angioplasty. RESULTS: Immunohistochemical studies in rabbit and porcine models suggest that C(6)-ceramide-coated balloon catheters limit arterial stenosis without inhibiting endothelial wound healing responses. Specifically, C(6)-ceramide-coated balloon catheters reduce internal elastica injury with a corresponding reduction in medial fracture length in a 28-day porcine coronary artery stretch model. In addition, C(6)-ceramide decreases the formation of the fibrin matrix to possibly augment the subsequent wound healing response. We hypothesized that differential metabolism of exogenous ceramide by coronary endothelial and smooth muscle cells could explain the apparent discrepancy between the anti-proliferative actions of ceramide and the pro-wound healing responses of ceramide. Human coronary artery endothelial cells (HCAEC), in contrast to human coronary artery smooth muscle cells (HCASMC), preferentially express ceramide kinase and form ceramide-1-phosphate, which promotes endothelial cell survival. CONCLUSION: Differential metabolism of ceramide between HCASMC and HCAEC offers a mechanism by which ceramide preferentially limits smooth muscle cell growth, in the presence of active wound healing. The combinatorial ability of ceramide to limit vascular smooth muscle proliferation and promote re-endothelialization, offers the potential for C(6)-ceramide-coated catheters to serve as adjuncts to stent-based modalities or as a stand-alone treatment.

Mitral valve repair complicated by left circumflex coronary artery occlusion: An under-recognized but potentially deadly complication.

Mitral valve repair is becoming an increasingly frequent surgery for patients with mitral valve regurgitation. Iatrogenic coronary artery injury and ischemic myocardial compromise have been previously reported in the literature as a rare but serious complication of surgical mitral valve repair. This potentially life-threatening complication should be considered and quickly recognized during perioperative mitral valve repair or replacement to prevent morbidity and mortality. To increase awareness and to prevent this complication from being missed in the future, we present a case report of iatrogenic left circumflex artery dynamic occlusion and subsequent myocardial infarction from mitral valve annuloplasty resulting in severe peri-operative heart failure and death.

Death and Dialysis After Transcatheter Aortic Valve Replacement: An Analysis of the STS/ACC TVT Registry.

OBJECTIVES: The authors sought to elucidate the true incidence of renal replacement therapy (RRT) after transcatheter aortic valve replacement (TAVR). BACKGROUND: There is a wide discrepancy in the reported rate of RRT after TAVR (1.4% to 40%). The true incidence of RRT after TAVR is unknown. METHODS: The STS/ACC TVT (Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy) registry was linked to the Centers for Medicare & Medicaid database to identify all patients that underwent TAVR from November 2011 through September 2015 and their outcomes. The authors compared rates of death, new RRT, and a composite of both as a function of pre-procedure glomerular filtration rate (GFR), both in stages of chronic kidney disease (CKD), as well as on a continuous scale. RESULTS: Pre-procedure GFR is associated with the risk of death and new RRT after TAVR when GFR is <60 ml/min/m2, and increases significantly when GFR falls below 30 ml/min/m2. Incremental increases in GFR of 5 ml/min/m2 were statistically significant (unadjusted hazard ratio: 0.71; p < 0.001) at 30 days, and continued to be significant at 1 year when pre-procedure GFR was <60 ml/min/m2. One in 3 CKD stage 4 patients will be dead within 1 year, with 14.6% (roughly 1 in 6) requiring dialysis. In CKD stage 5, more than one-third of patients will require RRT within 30 days; nearly two-thirds will require RRT at 1 year. CONCLUSIONS: In both unadjusted and adjusted analysis, pre-procedural GFR was associated with the outcomes of death and new RRT. Increasing CKD stage leads to an increased risk of death and/or RRT. Continuous analysis showed significant differences in outcomes in all levels of CKD when GFR was <60 ml/min/m2. Pre-procedure GFR should be considered when selecting CKD patients for TAVR.

Altered energy state reversibly controls smooth muscle contractile function in human saphenous vein during acute hypoxia-reoxygenation: Role of glycogen, AMP-activated protein kinase, and insulin-independent glucose uptake.

Hypoxia is known to promote vasodilation of coronary vessels through several mediators including cardiac-derived adenosine and endothelium-derived prostanoids and nitric oxide. To date, the impact of endogenous glycogen depletion in vascular smooth muscle and the resultant alterations in cellular energy state (e.g., AMP-activated protein kinase, AMPK) on the contractile response to G protein-coupled receptor agonists (e.g., serotonin, 5-HT) has not yet been studied. In the present study, ex vivo exposure of endothelium-denuded human saphenous vein rings to hypoxic and glucose-deprived conditions during KCl-induced contractions for 30 min resulted in a marked depletion of endogenous glycogen by ∼80% (from ∼1.78 µmol/g under normoxia to ∼0.36 µmol/g under hypoxia). Importantly, glycogen-depleted HSV rings, which were maintained under hypoxia/reoxygenation and glucose-deprived conditions, exhibited significant increases in basal AMPK phosphorylation (∼6-fold ↑) and 5-HT-induced AMPK phosphorylation (∼19-fold ↑) with an accompanying suppression of 5-HT-induced maximal contractile response (∼68% ↓), compared with respective controls. Exposure of glycogen-depleted HSV rings to exogenous D-glucose, but not the inactive glucose analogs, prevented the exaggerated increase in 5-HT-induced AMPK phosphorylation and restored 5-HT-induced maximal contractile response. In addition, the ability of exogenous D-glucose to rescue cellular stress and impaired contractile function occurred through GLUT1-mediated but insulin/GLUT4-independent mechanisms. Together, the present findings from clinically-relevant human saphenous vein suggest that the loss of endogenous glycogen in vascular smooth muscle and the resultant accentuation of AMPK phosphorylation by GPCR agonists may constitute a yet another mechanism of metabolic vasodilation of coronary vessels in ischemic heart disease.

Usefulness of temporary left ventricular pacing through the coronary sinus as an adjunct to transfemoral percutaneous coronary intervention.

In 10 patients who underwent percutaneous coronary intervention involving the right coronary artery, a new procedure for adjunctive temporary transfemoral pacing of the left ventricle through the coronary sinus was tested. The procedure was successful in 8 of 10 patients and could be performed in <5 minutes by experienced operators and supervised cardiology fellows.

High numbers of false-positive stress tests are the result of inappropriate testing.

Patients who underwent coronary angiography preceded by stress testing during the period January 2009 through March 2012 were evaluated using the CathPCI database. The predictive accuracy of stress echocardiography (SE) and single-photon emission computed tomography (SPECT) were determined and used to back calculate the pretest probability of the population being tested. In total, 2662 catheterizations were performed, 866 (33%) of which were preceded by stress imaging. Overall, the positive predictive values of SE and SPECT did not differ significantly (61% and 66%, P = .15) and were much lower in certain subgroups. The overall pretest probabilities of patients without a documented history of coronary artery disease undergoing SE and SPECT in the study population were estimated to be 18% and 27%, respectively. This study shows that stress testing is performed too often in low-risk patients in whom it is unlikely to improve clinical decision making.

Applying the diamond criteria could improve utilization of stress echocardiography for patients who present to the emergency department with low-risk chest pain.

We identified all patients with age 21 years and older, without a history of obstructive coronary artery disease, who presented to the emergency department with chest pain, and were admitted for cardiac observation followed by stress echocardiography during a 1-year period. The positive predictive value of stress echocardiography and cardiovascular outcomes were compared based on patients' Diamond chest pain classification. In patients with typical chest pain, who accounted for 8.7% (44/503) of the total cohort, the positive predictive value of stress echocardiography was 75% compared with 0% for all other subgroups (P = 0.007). Six patients (14%) with typical chest pain went on to have coronary revascularization compared with 0% for all other subgroups (P < 0.001). No patient in any subgroup died or was readmitted with a myocardial infarction in 30 days. Applying the Diamond criteria could improve utilization of stress echocardiography for patients with low-risk chest pain in the emergency department.

Spontaneous coronary artery dissection: a case series highlighting diagnostic challenges and the potential for underestimating the incidence of this presumed rare disorder.

Spontaneous coronary artery dissection (SCAD) is an uncommon condition with a variety of clinical presentations. Our knowledge base for SCAD is limited and derives from case reports and retrospective reviews. Several aspects of this disorder, including its rarity, heterogeneity of its presentation, and lack of identification during initial assessment, propose obstacles to reliably secure an accurate diagnosis and consequently we believe that the incidence of this disorder is likely underestimated in the literature. We present a case series of 5 patients with SCAD who exhibit features of this disorder that pose diagnostic challenges and outline the aspects of their history, presentation, and work-up. We propose that this condition is more than rare and may be underestimated; improved awareness of this disorder and associated trends might improve a clinician's index of suspicion and lead to a better diagnostic approach. Case reports and reviews remain vital to our understanding of this disorder and its true prevalence.

Nitrite consumption in ischemic rat heart catalyzed by distinct blood-borne and tissue factors.

Nitric oxide (NO) may limit myocardial ischemia-reperfusion injury by slowing the mitochondrial metabolism. We examined whether rat heart contains catalysts potentially capable of reducing nitrite to NO during an episode of regional myocardial ischemia produced by temporary coronary artery occlusion. In intact Sprague-Dawley rats, a 15-min coronary occlusion lowered the nitrite concentration of the myocardial regions exhibiting ischemic glucose metabolism to approximately 50% that of nonischemic regions (185 +/- 223 vs. 420 +/- 203 nmol/l). Nitrite was rapidly repleted during subsequent reperfusion. The heart tissue tested in vitro acquired a substantial ability to consume nitrite when made hypoxic at neutral pH, and this ability was slightly enhanced by simultaneously lowering the pH to 5.5. More than 70% of this activity could be abolished by flushing the coronary circulation with crystalloid to remove trapped erythrocytes. Correspondingly, erythrocytes demonstrated the ability to reduce exogenous nitrite to NO under hypoxic conditions in vitro. In erythrocyte-free heart tissue, the nitrite consumption increased fivefold when the pH was lowered to 5.5. Approximately 40% of this pH-sensitive increase in nitrite consumption could be blocked by the xanthine oxidoreductase inhibitor allopurinol, whereas lowering the Po(2) sufficiently to desaturate myoglobin accelerated it further. We conclude that rat heart contains several factors capable of catalyzing ischemic nitrite reduction; the most potent is contained within erythrocytes and activated by hypoxia, whereas the remainder includes xanthine oxidoreductase and other pH-sensitive factors endogenous to heart tissue, including deoxymyoglobin.