Diastolic dysfunction and clinical outcomes after transcatheter or surgical aortic valve replacement in patients with atypical aortic valve stenosis.

BACKGROUND: Diastolic dysfunction is a predictor of poor outcomes in many cardiovascular conditions. At present, it is unclear whether diastolic dysfunction predicts adverse outcomes in patients with atypical aortic stenosis who undergo aortic valve replacement (AVR). METHODS: Five hundred and twenty-three patients who underwent transcatheter AVR (TAVR) (n = 303) and surgical AVR (SAVR) (n = 220) at a single institution were included in our analysis. Baseline left and right heart invasive hemodynamics were assessed. Baseline transthoracic echocardiograms were reviewed to determine aortic stenosis subtype and parameters of diastolic dysfunction. Aortic stenosis subtype was categorized as typical (normal flow, high-gradient) aortic stenosis, classical, low-flow, low-gradient (cLFLG) aortic stenosis, and paradoxical, low-flow, low-gradient (pLFLG) aortic stenosis. Cox proportional hazard models were utilized to examine the relation between invasive hemodynamic or echocardiographic variables of diastolic dysfunction, aortic stenosis subtype, and all-cause mortality. Propensity-score analysis was performed to study the relation between aortic stenosis subtype and the composite outcome [death/cerebrovascular accident (CVA)]. RESULTS: The median STS risk was 5.3 and 2.5% for TAVR and SAVR patients, respectively. Relative to patients with typical aortic stenosis, patients with atypical (cLFLG and pLFLG) aortic stenosis displayed a significantly higher prevalence of diastolic dysfunction (LVEDP ≥ 20mmHg, PCWP ≥ 20mmHg, echo grade II or III diastolic dysfunction, and echo-PCWP ≥ 20mmHg) and, independently of AVR treatment modality, had a significantly increased risk of death. In propensity-score analysis, patients with atypical aortic stenosis had higher rates of death/CVA than typical aortic stenosis patients, independently of diastolic dysfunction and AVR treatment modality. CONCLUSION: We demonstrate the novel observation that compared with patients with typical aortic stenosis, patients with atypical aortic stenosis have a higher burden of diastolic dysfunction. We corroborate the worse outcomes previously reported in atypical versus typical aortic stenosis and demonstrate, for the first time, that this observation is independent of AVR treatment modality. Furthermore, the presence of diastolic dysfunction does not independently predict outcome in atypical aortic stenosis regardless of treatment type, suggesting that other factors are responsible for adverse clinical outcomes in this higher risk cohort.

A goal-oriented hemodynamic approach to acute myocardial infarction complicated by cardiogenic shock-A single center experience.

BACKGROUND: Acute myocardial infarction complicated by cardiogenic shock (AMI-CS) is the most common cause of mortality following AMI, and treatment algorithms vary widely. We report the results of an analysis using time-sensitive, hemodynamic goals in the treatment of AMI-CS in a single center study. METHODS: Consecutive patients with AMI-CS from November 2016 through December 2021 were included in our retrospective analysis. Clinical characteristics and outcomes were analyzed using the electronic medical records. We identified 63 total patients who were admitted to our center with AMI-CS, and we excluded patients who did not have clear timing of AMI onset or CS onset. We evaluated the rate of survival to hospital discharge based on the quantity of certain time-sensitive hemodynamic goals were met. RESULTS: We identified 63 patients who met criteria for AMI-CS, 39 (62%) of whom survived to hospital discharge. Odds of survival were closely related to the achievement of four time-dependent goals: cardiac power output (CPO) >0.6 Watts (W), pulmonary artery pulsatility index (PAPi) >1, lactate <4 mmol/L, and <2 vasopressors required. Of the 63 total patients, 36 (57%) received intra-aortic balloon pump (IABP) and 18 (29%) received an Impella CP (Abiomed) as an initial mechanical circulatory support strategy. Six patients were escalated from IABP to Impella CP for additional hemodynamic support. Nine patients were treated with vasopressors/inotropes alone. Regarding the 39 patients who survived to hospital discharge, 75% of patients met 3 or 4 goals at 24 h, whereas only 16% of deceased patients met 3 or 4 goals at 24 h. Of the 24 patients who did not survive to hospital discharge, 18 (75%) met either 0-1 goal at 24 h. There was no effect of the initial treatment strategy on achieving 3-4 goals at 24 h. CONCLUSION: Our study evaluated the association of meeting 4 time-sensitive goals (CPO >0.6 W, PAPi >1, <2 vasopressors, and lactate <4 mmol/L) at 24 h after treatment for AMI-CS with in-hospital mortality. Our data show, in line with previous data, that the higher number of goals met at 24 h was associated with improved in-hospital mortality regardless of treatment strategy.

Differential Neutralization of Apixaban, Betrixaban, Edoxaban, and Rivaroxaban by Andexanet Alfa as Measured by Whole Blood Thromboelastographic Analysis.

INTRODUCTION: The available oral anti-Xa agents are routinely used for the management of thrombotic disorders. A molecularly modified recombinant coagulation FXa, also known as Andexanet Alfa (AA), that has been developed as an antidote to neutralize the bleeding effects of oral FXa inhibitors, such as Apixaban and Rivaroxaban. MATERIALS AND METHODS: This study utilized thromboelastography (TEG 5000 Hemostasis System), to investigate the neutralizing effects of AA at different concentrations of oral FXa inhibitors measuring such parameters as R-Time, K-Time, Angle, and Max Amplitude (MA). Apixaban, Betrixaban, Edoxaban, and Rivaroxaban were obtained commercially in powdered form. Each of these drugs was supplemented with freshly drawn whole citrated blood at a concentration of 1 µg/mL. And subsequently mixed with AA at 50 or 100 µg/mL. RESULTS: At a concentration of 1 µg/mL, all FXa inhibitors produced variable anticoagulant effects in the order of Edoxaban > Betrixaban > Rivaroxaban > Apixaban. AA at 100 µg/mL produced a complete neutralization of these inhibitors whereas at 50 µg/mL relatively weaker neutralization as measured by various parameters. CONCLUSION: These results suggest that regardless of the variable anticoagulant effects exhibited by the FXa Inhibitors, AA at FC = 100 µg/mL fully neutralized these agents as measured by the TEG parameters. AA was shown to be more effective in neutralizing Betrixaban and least effective in Apixaban. The neutralization of various FXa inhibitors was dose and donor-dependent warranting dosage adjustment for optimal outcomes.

An Update on the Pathogenesis of COVID-19 and the Reportedly Rare Thrombotic Events Following Vaccination.

Today the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become a global health problem. After more than a year with the pandemic, although our knowledge has progressed on COVID-19, there are still many unknowns in virological, pathophysiological and immunological aspects. It is obvious that the most efficient solution to end this pandemic are safe and efficient vaccines. This manuscript summarizes the pathophysiological and thrombotic features of COVID-19 and the safety and efficacy of currently approved COVID-19 vaccines with an aim to clarify the recent concerns of thromboembolic events after COVID-19 vaccination. The influx of newer information is rapid, requiring periodic updates and objective assessment of the data on the pathogenesis of COVID-19 variants and the safety and efficacy of currently available vaccines.

Technical success and long-term outcomes after anomalous right coronary artery stenting with cardiac computed tomography angiography correlation.

INTRODUCTION: Anomalous origin of coronary arteries has been observed in about 0.35-2.10% of the population. Patients with anomalous right coronary artery (ARCA) may present with significant symptoms, arrhythmias or ACS, and at times sudden death. Traditionally, surgical correction has been the recommended treatment. However, these may be technically challenging, and bypass grafting for such anomalies has the potential for graft failure because of competitive flow. We sought to determine the intermediate and long-term outcomes of drug-eluting stent placement for patients with symptomatic ARCA. We also looked at angiographic findings suggestive of interarterial course as confirmed by subsequent computed tomography (CT) findings. METHODS: Between January 2005 and December 2012, we enrolled 11 patients for elective percutaneous coronary intervention (PCI) of ARCA in a single center, prospective, nonrandomized fashion. Patients were followed up in clinic at 1 week, 3 months, 6 months, and 1 year, and then annually or more frequently if needed. All patients underwent a cardiac CT, as well as functional stress testing when needed to assess for recurrence of disease. RESULTS: All 11 of our patients, who presented with significant symptomatic stenosis with an ARCA, were successfully treated with PCI. Mean follow-up duration was 8.5 years. The only two deaths during follow-up were related to noncardiac causes (sepsis), with a mortality rate of 18.2%. Two patients had a positive functional study and on subsequent coronary angiography, one of them had significant in-stent restenosis (target lesion revascularization of 9.1%) and one distal to the stent (target vessel revascularization 9.1%). We found the observation of a "slit-like lesion" on angiography to have a sensitivity of 100% and specificity of 86% for the diagnosis of interarterial course of the anomalous vessel seen on subsequent CT. CONCLUSIONS: Our study results suggest that PCI of ARCA is an effective and low-risk alternative to surgical correction, with good procedural success and long-term outcomes. It can provide symptomatic relief in such patients and may reduce the risk of sudden death in younger patients, without the inherent risks associated with surgical repair.

Impact of Emergency Medical Services Activation of the Cardiac Catheterization Laboratory and a 24-Hour/Day In-Hospital Interventional Cardiology Team on Treatment Times (Door to Balloon and Medical Contact to Balloon) for ST-Elevation Myocardial Infarction.

The incremental benefit of emergency medical services (EMS) activation of the cardiac catheterization laboratory (CCL) for ST-elevation myocardial infarction (STEMI) in the setting of an established in-house interventional team (IHIT) is uncertain. We evaluated the impact of EMS activation on door-to-balloon (D2B) time and first medical contact-to-balloon (FMC2B) time for STEMI when coupled with a 24-hour/day IHIT. All patients presenting with STEMI to Loyola University Medical Center had demographic, procedural, and outcome data consecutively entered in a STEMI Data Registry. From 223 consecutive patients presenting between April 2009 and December 2015, a retrospective analysis was performed on 190 patients. Patients were divided into 2 groups depending on CCL activation mode (EMS activation or emergency department activation) and STEMI treatment process times were compared. The primary end point was D2B process times. The secondary end point was FMC2B process times in a subgroup analysis of EMS-transported patients. D2B times were shorter (37 ± 14 minutes vs 57 ± 27 minutes, p < 0.001) with EMS activation. Subgroup analysis of EMS-transported patients demonstrated shorter FMC2B times with EMS activation (52 ± 17 minutes vs 67 ± 32 minutes, p = 0.002). EMS activation was the only predictor of D2B ≤60 minutes in multivariable analysis of EMS-transported patients (odds ratio 9.4; 95% confidence interval 2.1 to 43.0; p = 0.04). In conclusion, EMS activation of the CCL in STEMI was associated with significant improvements in already excellent D2B and FMC2B times even in the setting of a 24-hour/day IHIT.

Meta-Analysis of Studies Comparing Dual- Versus Mono-Antiplatelet Therapy Following Transcatheter Aortic Valve Implantation.

Current guidelines recommend dual-antiplatelet therapy (DAPT) after transcatheter aortic valve implantation (TAVI), although some studies suggest mono-antiplatelet therapy is equally efficacious with an improved safety profile. We performed a meta-analysis of studies comparing DAPT with mono-antiplatelet therapy after TAVI. Study quality and heterogeneity were assessed using Jadad score, Newcastle-Ottawa Scale, and Cochran's Q statistics. Mantel-Haenszel odds ratios (ORs) were calculated using fixed effect models as the primary analysis. Eight studies including 2,439 patients met the inclusion criteria. At 30 days, DAPT was associated with an increased risk of all-cause mortality (OR 2.06, 95% confidence interval [CI] 1.34 to 3.18, p = 0.001), major or life-threatening bleeding (OR 2.04, 95% CI 1.60 to 2.59, p <0.001), and major vascular complications (OR 2.15, 95% CI 1.51 to 3.06, p <0.001). There was no difference in the rate of the combined end point of stroke or transient ischemic attack, or myocardial infarction. Outcome data up to 6 months were available in 5 studies; all-cause mortality and stroke were similar between groups, although major or life-threatening bleeding was more frequent with DAPT. In conclusion, in patients undergoing TAVI, DAPT is associated with increased risk at 30 days of all-cause mortality, major or life-threatening bleeding, and major vascular complications without a decrease in ischemic complications; at 6 months, the excess bleeding risk persisted. These data suggest a safety concern with DAPT and justify further investigation of the optimal antiplatelet therapy regimen after TAVI.

Endovascular Repair of Bilateral Internal Mammary Artery Aneurysms in a Patient with Marfan Syndrome-A Case Report.

Marfan syndrome (MFS) is an autosomal dominant condition that is caused by abnormal synthesis of connective tissue. The syndrome classically affects the ocular, musculoskeletal, and cardiovascular systems. The most common cardiovascular manifestations include mitral valve prolapse/regurgitation and aortic aneurysms at high risk of rupture and dissection. However, internal mammary artery (IMA) true aneurysms are rarely reported. In this case report, we describe a 43-year-old male patient with MFS and three previous thoracotomies referred for endovascular repair of bilateral IMA true aneurysms. To the best of our knowledge, there are no cases of endovascular treatment of bilateral IMA true aneurysms reported in the literature.

Comparison of primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction during and prior to availability of an in-house STEMI system: early experience and intermediate outcomes of the HARRT program for achieving routine D2B times <60 minutes.

BACKGROUND: Over the last decade, significant advances in ST-elevation myocardial infarction (STEMI) workflow have resulted in most hospitals reporting door-to-balloon (D2B) times within the 90 min standard. Few programs have been enacted to systematically attempt to achieve routine D2B within 60 min. We sought to determine whether 24-hr in-house catheterization laboratory coverage via an In-House Interventional Team Program (IHIT) could achieve D2B times below 60 min for STEMI and to compare the results to the standard primary percutaneous coronary intervention (PCI) approach. METHODS: An IHIT program was established consisting of an attending interventional cardiologist, and a catheterization laboratory team present in-hospital 24 hr/day. For all consecutive STEMI patients, we compared the standard primary PCI approach during the two years prior to the program (group A) to the initial 20 months of the IHIT program (group B), and repeated this analysis for only CMS-reportable patients. The D2B process was analyzed by calculating workflow intervals. The primary endpoint was D2B process times, and secondary endpoints included in-hospital and 6-month cardiovascular outcomes and resource utilization. RESULTS: An IHIT program for STEMI resulted in significant reductions across all treatment intervals with an overall 57% reduction in D2B time, and an absolute reduction in mean D2B time of 71 min. There were no differences pre- and post-program implementation in regard to individual or composite components of in-hospital cardiovascular outcomes; however at 6 months, there was a reduction in cardiovascular rehospitalization after program implementation (30 vs. 5%, P < 0.01). The IHIT program resulted in a significant reduction in length-of-stay (LOS) (90 ± 102 vs. 197 ± 303 hr, P = 0.02), and critical care time (54 ± 97 vs. 149 ± 299 hr, P = 0.02). CONCLUSIONS: Availability of an in-house 24-hr STEMI team significantly decreased reperfusion time and led to improved clinical outcomes and a shorter LOS for PCI-treated STEMI patients.

Nonhemostatic adverse effects of anticoagulants and antiplatelet agents.

The topic of adverse effects of drugs is now receiving due attention in both the lay and medical communities. For drugs of the coagulation disorder class, such as anticoagulants and antiplatelet agents, the obvious adverse effects are bleeding from a dose too high and thrombosis from a dose too low. However, these drugs have other potential adverse effects that are not directly related to blood coagulation, yet cannot be dismissed due to their medical importance. There has been a recent advancement of several new drugs in this category and this number will soon grow as more drugs are reaching the end of their clinical trials. This article will discuss the nonhemostatic adverse effects of anticoagulants and antiplatelet drugs. As the adverse effects of bleeding and thrombosis will be excluded, this article will be in contrast to the typical discussions on the anticoagulant and antiplatelet drug classes.

Oral factor Xa and direct thrombin inhibitors: a clinical perspective.

Oral anticoagulation used to be synonymous with warfarin until the recent approval of oral direct thrombin inhibitors and factor Xa inhibitors in United States and other countries across the world. Thrombosis prevention and treatment continue to be the main objective and goal for surgical and medical patients. Regulatory agencies continue to revise their guidelines to treat these patients with appropriate medication and for optimal duration. As the choices for oral anticoagulants increase, with many oral anticoagulant drugs currently in the pipeline awaiting completion of clinical trials, the guidelines for venous thromboembolism prevention, stroke prevention in atrial fibrillation, and treatment of acute arterial and venous thrombi will also shift from the current standards to new standards set by these clinical trials for optimal dosing and duration of treatment. However, it must be reinforced that these new oral anticoagulants are distinct pharmacological compounds with specific targets and will also have distinct clinical indications for use.

An open label, non-randomized, prospective clinical trial evaluating the immunogenicity of branded enoxaparin versus biosimilars in healthy volunteers.

INTRODUCTION: Compositional variations among biosimilar enoxaparin could lead to a differential immunogenic response between these preparations. METHODS: Enoxaparin (Clexane, n = 110) and a biosimilar version (Cutenox, n = 110) were administered to healthy volunteers in Brazil, 40 mg subcutaneous (SQ), daily, for 10 days. Blood was collected at baseline, days 1 and 10, and analyzed for antiheparin/PF4 antibody (AHPF4 antibodies) titers and subtypes by enzyme-linked-immunosorbent serologic assay (ELISA). RESULTS: Low-molecular-weight heparin (LMWH) treatment resulted in AHPF4 antibodies generation, with differences on day 10 (P < .05). Antibody subtyping (immunoglobulin [Ig] G, IgA, IgM) demonstrated different profiles between LMWH with statistical significance for IgG (Clexane 10 = 0.21 ± 0.06, Cutenox 10 = 0.28 ± 0.10, P < .0001) and IgA (Clexane 10 = 0.15 ± 0.02, versus Cutenox 10 = 0.13 ± 0.02, P < .0001) on day 10, with a significant drug effect (P < .0001) and significant time by drug interaction (P = .0009). All antibody titers were stated in terms of optical density (OD) units. CONCLUSION: LMWHs immunogenic potential varies to generate AHPF4 antibodies and subtypes and cross-reactivity with preformed antibodies. Such parameters may be useful in defining the biosimilar LMWHs bioequivalence. Future studies evaluating the immunogenicity of biosimilar drugs are warranted.

Pharmacology of argatroban.

Argatroban is a synthetic, small-molecule direct thrombin inhibitor that is approved in the USA, the EU and Japan for prophylaxis or treatment of thrombosis in patients with heparin-induced thrombocytopenia (HIT), and for anticoagulation of HIT patients undergoing PCI. Argatroban binds reversibly to, and inhibits both soluble and clot-bound thrombin. Argatroban does not generate antibodies, is not susceptible to degradation by proteases and is cleared hepatically. It has a predictable anticoagulant effect and there is a good correlation between dose, plasma concentration and pharmacodynamic effect. Initial clinical studies suggest that further investigations to establish the use of argatroban in ischemic stroke, acute coronary syndrome, hemodialysis, blood oxygenation, off-pump cardiac surgery and other clinical indications are warranted.

Usefulness of wide pulse pressure as a predictor of poor outcome after renal artery angioplasty and stenting.

Renal artery stenosis is a common cause of secondary hypertension and ischemic nephropathy. Percutaneous angioplasty and stent placement has allowed select patients with renal artery stenosis to use fewer antihypertensive agents and improve or stabilize renal function. The associations of baseline systolic, diastolic, and pulse pressures (PPs) with outcomes of blood pressure (BP) and renal function were examined in 243 patients who underwent renal angioplasty and stent placement. The average PP before the procedure in patients with improvements or stabilizations in renal function was 53 +/- 20 mm Hg, compared to 107 +/- 18 mm Hg (p <0.05) in those with poorer outcomes. The average PPs before procedure were 47 +/- 15 mm Hg in those with improvements in BP, 82 +/- 10 mm Hg in those with stabilizations of BP, and 111 +/- 14 mm Hg in those with worsening BP. All findings were statistically significant (p <0.05). In conclusion, wide PP may reflect more advanced vascular stiffness and renal disease distinguishing patients less likely to benefit from revascularization.

Renal artery dissection following marathon running.

A 38-year-old, previously healthy man presented with flank pain after competing in a marathon. Initial laboratory tests and urinalysis were essentially normal. Both contrast enhanced-computed tomography and magnetic resonance angiography showed an infarcted region of the left lower kidney without renal artery dissection. Thromboembolism was suspected, but further testing was negative. The diagnosis of renal artery dissection was established by angiogram, showing dissection of the segmental branch. The patient remained normotensive, maintained normal renal function, and had resolution of pain symptoms prior to discharge. On the basis of our experience and review of the literature, renal artery dissection occurs in otherwise healthy men and often goes undiagnosed. The management strategy tends to be conservative unless the patient develops progressive decline in renal function or worsening hypertension, with an excellent prognosis. This case also shows the importance of discussing the pros and cons of extreme physical exertion with all patients.

Percutaneous coronary intervention in patients with acute coronary syndrome: focus on bivalirudin.

Previously, indirect thrombin inhibitors such as unfractionated heparin or low-molecular-weight heparin were used as a standard anticoagulation during percutaneous coronary intervention to prevent procedural thrombotic complications but at a risk of hemorrhagic complications. More recently, bivalirudin, a member of the direct thrombin inhibitor class, has been shown to have 1) predictable pharmacokinetics, 2) ability to inhibit free- and clot-bound thrombin, 3) no properties of platelet activation, 4) avoidance of heparin-induced thrombocytopenia, and 5) a significant reduction of bleeding without a reduction in thrombotic or ischemic endpoints compared to heparin and glycoprotein IIbIIIa inhibitors when used in patients presenting with acute coronary syndrome who are planned for an invasive treatment strategy.