Transesophageal Echocardiographic Screening for Structural Heart Interventions.

PURPOSE OF REVIEW: Percutaneous structural interventions have provided patients with an effective therapeutic option, and its growth has been aided by echocardiography. We describe the vital role that transesophageal echocardiography (TEE) plays in screening patients prior to their procedure. RECENT FINDINGS: A multimodality imaging approach is employed by the valve team, but TEE plays a unique role in diagnosis and planning. Utilization of all TEE views and features such as biplane, 3D imaging, and multiplanar reconstruction ensures accurate assessment of the structural lesion of interest. The role of TEE remains essential in the planning of structural interventions, and these studies should be performed in a systematic and comprehensive manner.

Long-term outcomes after transcatheter aortic valve replacement with minimal contrast in chronic kidney disease.

BACKGROUND: Patients with renal insufficiency have poor short-term outcomes after transcatheter aortic valve replacement (TAVR). METHODS: Retrospective chart review identified 575 consecutive patients not on hemodialysis who underwent TAVR between September 2014 and January 2017. Outcomes were defined by VARC-2 criteria. Primary outcome of all-cause mortality was evaluated at a median follow-up of 811 days (interquartile range 125-1,151). RESULTS: Preprocedural glomerular filtration rate (GFR) was ≥60 ml/min in 51.7%, 30-60 ml/min in 42.1%, and < 30 ml/min in 6.3%. Use of transfemoral access (98.8%) and achieved device success (91.0%) did not differ among groups, but less contrast was used with lower GFR (23 ml [15-33], 24 ml [14-33], 13 ml [8-20]; p < .001). Peri-procedural stroke (0.7%, 2.1%, 11.1%; p < .001) was higher with lower GFR. Core lab analysis of preprocedural computed tomography scans of patients who developed a peri-procedural stroke identified potential anatomic substrate for stroke in three out of four patients with GFR 30-60 ml/min and all three with GFR <30 ml/min (severe atheroma was the most common subtype of anatomical substrate present). Compared to GFR ≥60 ml/min, all-cause mortality was higher with GFR 30-60 ml/min (HR 1.61 [1.00-2.59]; aHR 1.61 [0.91-2.83]) and GFR <30 ml/min (HR 2.41 [1.06-5.48]; aHR 2.34 [0.90-6.09]) but not significant after multivariable adjustment. Follow-up echocardiographic data, available in 63%, demonstrated no difference in structural heart valve deterioration over time among groups. CONCLUSIONS: Patients with baseline renal insufficiency remain a challenging population with poor long-term outcomes despite procedural optimization with a transfemoral-first and an extremely low-contrast approach.

Early outcomes from the CLASP IID trial roll-in cohort for prohibitive risk patients with degenerative mitral regurgitation.

OBJECTIVES: We report the 30-day outcomes from the roll-in cohort of the CLASP IID trial, representing the first procedures performed by each site. BACKGROUND: The currently enrolling CLASP IID/IIF pivotal trial is a multicenter, prospective, randomized trial assessing the safety and effectiveness of the PASCAL transcatheter valve repair system in patients with clinically significant MR. The trial allows for up to three roll-in patients per site. METHODS: Eligibility criteria were: DMR ≥3+, prohibitive surgical risk, and deemed suitable for transcatheter repair by the local heart team. Trial oversight included a central screening committee and echocardiographic core laboratory. The primary safety endpoint was a 30-day composite MAE: cardiovascular mortality, stroke, myocardial infarction (MI), new need for renal replacement therapy, severe bleeding, and non-elective mitral valve re-intervention, adjudicated by an independent clinical events committee. Thirty-day echocardiographic, functional, and quality of life outcomes were assessed. RESULTS: A total of 45 roll-in patients with mean age of 83 years and 69% in NYHA class III/IV were treated. Successful implantation was achieved in 100%. The 30-day composite MAE rate was 8.9% including one cardiovascular death (2.2%) due to severe bleeding from a hemorrhagic stroke, one MI, and no need for re-intervention. MR≤1+ was achieved in 73% and ≤2+ in 98% of patients. 89% of patients were in NYHA class I/II (p < .001) with improvements in 6MWD (30 m; p = .054) and KCCQ (17 points; p < .001). CONCLUSIONS: Early results representing sites with first experience with the PASCAL repair system showed favorable 30-day outcomes in patients with DMR≥3+ at prohibitive surgical risk.

Therapeutic blockade of inflammation in severe COVID-19 infection with intravenous N-acetylcysteine.

Glucose 6-phosphate dehydrogenase (G6PD) deficiency facilitates human coronavirus infection due to glutathione depletion. G6PD deficiency may especially predispose to hemolysis upon coronavirus disease-2019 (COVID-19) infection when employing pro-oxidant therapy. However, glutathione depletion is reversible by N-acetylcysteine (NAC) administration. We describe a severe case of COVID-19 infection in a G6PD-deficient patient treated with hydroxychloroquine who benefited from intravenous (IV) NAC beyond reversal of hemolysis. NAC blocked hemolysis and elevation of liver enzymes, C-reactive protein (CRP), and ferritin and allowed removal from respirator and veno-venous extracorporeal membrane oxygenator and full recovery of the G6PD-deficient patient. NAC was also administered to 9 additional respirator-dependent COVID-19-infected patients without G6PD deficiency. NAC elicited clinical improvement and markedly reduced CRP in all patients and ferritin in 9/10 patients. NAC mechanism of action may involve the blockade of viral infection and the ensuing cytokine storm that warrant follow-up confirmatory studies in the setting of controlled clinical trials.

Preprocedural P2Y12 inhibition and decrease in platelet count following transcatheter aortic valve replacement.

BACKGROUND: Thrombocytopenia after transcatheter aortic valve replacement (TAVR) is associated with adverse clinical outcomes. Whether preprocedural P2Y12 inhibition prevents postprocedural thrombocytopenia is uncertain. METHODS: This retrospective analysis identified consecutive patients (n = 266) undergoing TAVR between November 2016 and July 2017. Preprocedure clopidogrel load ≥300 mg or maintenance P2Y12 inhibitor therapy defined preprocedural P2Y12 inhibition. Patients who did not consent for the registry (n = 8), with baseline severe thrombocytopenia (<90 × 103 platelets/µL; n = 14), or without baseline platelet count (n = 4) were excluded. The primary outcome was proportion of patients who developed >20% decrease in platelet count from baseline to day 1 post-TAVR. RESULTS: Patients with (n = 134) versus without (n = 106) preprocedural P2Y12 inhibition had no differences in platelet count at baseline. Patients with preprocedural P2Y12 inhibition had a significantly lower proportion of the primary outcome (34.3% vs. 57.5%, p = .001) and a lower absolute decrease in platelet count (32.8 × 103 vs. 45.8 × 103 platelet/µL, p = .01). Of patients without baseline thrombocytopenia (n = 198), a numerically lower rate of patients with versus without preprocedural P2Y12 inhibition developed thrombocytopenia on day 1 post-TAVR (25.5% vs. 36.4%, p = .1). CONCLUSION: Patients who received preprocedural P2Y12 inhibition prior to TAVR were less likely to demonstrate a decrease in platelet count after TAVR. Prospective studies to further understand the clinical implication of these findings are warranted.

Glycoprotein IIb/IIIa inhibitor use in patients with acute myocardial infarction undergoing PCI: Insights from the TRANSLATE ACS study.

INTRODUCTION: Concomitant use of glycoprotein IIb/IIIa inhibitors (GPI) and P2Y12 inhibitors increases bleeding risk. How GPIs are being used with faster onset, higher potency P2Y12 inhibitors are unclear. METHODS AND RESULTS: We studied 11,781 myocardial infarction (MI) patients treated with percutaneous coronary intervention (PCI) at 233 hospitals in the TRANSLATE ACS study (2010-2012). We used propensity matching to compare 6-week major adverse cardiac events (MACE: death, recurrent MI, stroke, or unplanned revascularization) and BARC 2+ bleeding events between patients who did and did not receive planned GPI. Planned and bailout GPI were used in 4,983 (42.2%) and 229 (4.4%) MI patients undergoing PCI, respectively. Patients receiving planned GPI were younger (58 vs. 61 years), more likely to present with STEMI (62.6% vs. 45.4%) or have stent thrombosis (4.2% vs. 2.1%, all P < 0.001) than those without planned GPI use. Planned GPI was used less often with prasugrel/ticagrelor versus clopidogrel (37.1% vs. 43.3%), or when any P2Y12 inhibitor was given >6 hr prior to PCI versus earlier (27.8% vs. 44.4%, both P < 0.01). After propensity matching, planned GPI use was not associated with any difference in MACE (6.4% vs. 5.5% OR 1.18; 95% CI: 0.99-1.57), however, the risk of BARC 2+ bleeding was higher in patients who received planned GPI (11.3% vs. 8.7%; OR 1.34; 95% CI: 1.13-1.59). CONCLUSION: Planned GPI use as reported by practicing physicians was prevalent between 2010 and 2012 and was associated with increased risk of bleeding but not lower MACE.

Antithrombotic drugs in cardiovascular medicine: a year in review.

PURPOSE OF REVIEW: To provide an up to date review of the most recent randomized clinical trials in the field of antithrombotic drugs for cardiovascular diseases. RECENT FINDINGS: In 2017, low-dose anti-Xa treatment added to aspirin proved to be more efficacious than either treatment alone in patients with stable atherosclerotic disease despite the increase in nonfatal bleeding events. Furthermore, anticoagulation strategy during coronary interventions was again tested in a registry-based trial and showed comparable efficacy and safety between heparin alone and bivalirudin. Data from safety trials demonstrated lower risk of bleeding with dual antithrombotic therapy compared with triple antithrombotic therapy following coronary intervention, albeit these trials were underpowered for efficacy. Although still in its infancy, the role of antithrombotic treatment following transcatheter aortic valve replacement (TAVR) has been investigated in small trials with evidence that a single antiplatelet drug may be noninferior to dual antiplatelet therapy with a better safety profile. SUMMARY: In this review, we discuss the most recent clinical trials investigating antithrombotic drugs for cardiovascular diseases published in 2017.

In-hospital outcomes of transcatheter versus surgical aortic valve replacement in end stage renal disease.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is an alternative to surgical aortic valve replacement (SAVR) for patients with severe symptomatic aortic stenosis (AS) who are at intermediate and high risk for surgery. Commercial use of TAVR has expanded to patients with end stage renal disease (ESRD). OBJECTIVES: Compare in-hospital outcomes of TAVR versus SAVR in ESRD patients requiring hemodialysis (HD). METHODS: ESRD patients on HD undergoing TAVR (n = 328) or SAVR (n = 697) between 2012 and 2014 were identified in the National Inpatient Sample (NIS). Propensity-score matching method was used to minimize selection bias. Baseline characteristics and in-hospital outcomes were compared. RESULTS: TAVR patients were older (75.3 vs. 61.6 years, P < 0.001) and had more comorbidities, including congestive heart failure (16.2% vs. 7.5%), diabetes mellitus (28.4% vs. 22.5%), chronic lung disease (27.7% vs. 20.4%), and peripheral vascular disease (35.1% vs. 21.2%). Propensity-score matching yielded 175 pairs of patients matched on 30 baseline covariates. Overall in-hospital mortality was high (9.9%) and similar between TAVR and SAVR (8% vs. 10.3%, P = 0.58). TAVR was associated with shorter length of stay (LOS) (8 vs. 14 days, P < 0.001), lower hospitalization cost ($276,448 vs. $364,280, P = 0.01), lower in-hospital complications (60.6% vs. 76%, P = 0.003), and higher rate of home discharge (31.4% vs. 17.7%, P = 0.004) compared with SAVR. CONCLUSIONS: Regardless of treatment modality, patients with AS on HD have high in-hospital mortality. TAVR and SAVR have comparable in-hospital mortality in this population. However, TAVR is associated with shorter LOS, lower hospitalization costs, lower in-hospital complications, and higher rates of home discharge.

Oral antiplatelet drugs in patients with chronic kidney disease (CKD): a review.

Oral Antiplatelet Drugs (OAD) have a proven track record in the risk reduction of major cardiovascular events in patients with cardiovascular disease and normal kidney function. However, major gaps exist in our understanding of their effects on thrombosis and bleeding in chronic kidney disease (CKD). Clinical practice guidelines are ambiguous about use of such drugs in CKD patients, because patients with moderate to severe CKD were systematically excluded from clinical trials evaluating the efficacy and safety of OAD. Paradoxically, CKD patients are at high risk of thrombosis and major bleeding events. Thus, choosing the right combination of OAD for cardiovascular protection in these patients is challenging. Patients with CKD exhibit high rates of OAD hyporesponsiveness. It is, therefore, imperative to explore the mechanisms responsible for poor response to OAD in CKD patients in order to use these drugs more safely and effectively. This review explores suggested mechanisms of platelet dysfucntion in CKD patients and the available evidence on the efficacy and safety of oral antiplatelet drugs in patients with renal dysfunction.

Detection and quantification of circulating immature platelets: agreement between flow cytometric and automated detection.

Immature platelets-also termed reticulated platelets (RP)-are platelets newly released into the circulation, and have been associated with a variety of pathological thrombotic events. They can be assessed by flow cytometry after staining with thiazole orange (TO) or by using a module added to a fully automated analyzer that is currently in wide clinical use and expressed as a fraction of the total platelet count (IPF). We sought to assess the correlation and agreement between these two methods. IPF was measured using Sysmex XE 2100-and at the same time point- we used TO staining and flow cytometry to measure RP levels. Two different gates were used for the flow cytometry method, 1 and 0.5 %. Measurements from the automated analyzer were then compared separately to measurements performed using each gate. Agreement between methods was assessed using Bland-Altman method. Pearson's correlation coefficient was also calculated. 129 subjects were enrolled and stratified into 5 groups: (1) Healthy subjects, (2) End stage renal disease, (3) Chronic stable coronary artery disease, (4) Post Coronary artery bypass surgery, (5) Peripheral thrombocytopenia. Median IPF levels were increased for patients in groups 2, 3, 4 and 5 (4.0, 4.7, 4.3, and 8.3 % respectively) compared to healthy subjects (2.5 %) p = 0.0001. Although the observed correlation between the two methods tended to be good in patients with high IPF values (i.e., group 5), the overall observed correlation was poor (Pearson's correlation coefficient r = 0.27). Furthermore, there was poor agreement between the two methods in all groups. Despite the good correlation that was observed between the two methods at higher IPF values, the lack of agreement was significant.

Clinical characteristics and in hospital outcomes of heart transplant recipients with allograft vasculopathy undergoing percutaneous coronary intervention: Insights from the National Cardiovascular Data Registry.

BACKGROUND: Cardiac allograft vasculopathy is a major cause of morbidity and mortality following heart transplantation. Large multicenter studies evaluating the clinical characteristics and inhospital outcomes of heart transplant recipients undergoing percutaneous coronary intervention (PCI) are lacking. OBJECTIVE: To evaluate the clinical characteristics, treatment patterns and inhospital outcomes of heart transplant recipients undergoing PCI compared to general population. METHODS: We analyzed 1,897,328 patients from the National Cardiovascular Data Registry CathPCI registry who underwent PCI of at least 1 native vessel between July 2009 and December 2013 from 1,477 centers, of which 542 patients (0.03%) were heart transplant recipients. Clinical characteristics were evaluated and, after 1:4 propensity matching, inhospital outcomes were compared between 538 heart transplant patients and 2,128 non-transplant patients. RESULTS: Transplant recipients undergoing PCI had a higher prevalence of diabetes, dyslipidemia and peripheral vascular disease; lower prevalence of angina, acute coronary syndrome, abnormal noninvasive functional study, and type C coronary lesions compared to the non-transplant PCI population. After propensity matching, all-cause inhospital mortality was similar between transplant and non-transplant groups (1.3% vs 1.0%; OR, 1.21; 95% CI, 0.54-2.67). CONCLUSION: This is the largest series to date outlining the characteristics of heart transplant recipients undergoing PCI. Similar inhospital outcomes were noted in heart transplant recipients compared to the general population. Further studies evaluating long-term outcomes are warranted.

Renal Denervation: Past, Present, and Future.

Hypertension remains a leading cause of cardiovascular morbidity and mortality worldwide. It is estimated that 12.8% of hypertensive adults have resistant hypertension. The sympathetic nervous system is a well-known contributor to the pathophysiology of resistant hypertension. Renal denervation has emerged as an effective procedure to treat resistant hypertension by blocking the sympathetic nervous system. The medical device industry has developed various catheters in an effort to achieve better denervation in the absence of available testing to document adequate denervation. By adding a sham control group to the study design, researchers found that the results of the Renal Denervation in Patients With Uncontrolled Hypertension study (SYMPLICITY HTN-3) showed that renal denervation was not superior to placebo in decreasing systolic blood pressure. Although SYMPLICITY HTN-3 successfully addressed many issues that might have biased the previously published data, incomplete denervation caused by limited operator experience, catheter design, and the radiofrequency ablation technology may have accounted for the discrepancy of the results. This, along with differences in the study design and population, should direct future renal denervation studies. This article reviews the available literature and proposes future directions for renal denervation studies. It also provides a detailed comparison of the available catheters and their respective clinical data.

Coronary Artery Obstruction After Transcatheter Aortic Valve Implantation: Past, Present, and Future.

Coronary obstruction (CO) is a rare but critical complication of transcatheter aortic valve implantation. It is associated with significant morbidity and mortality. This comprehensive review elucidates the evolving landscape of CO risk assessment and management strategies in the contemporary era of transcatheter aortic valve implantation. Drawing upon recent advances in computed tomography angiography, we delve into the nuanced evaluation of anatomic parameters crucial for predicting CO risk. Furthermore, this review explores the utility of interventional and surgical techniques, including chimney stenting and leaflet modification systems, in mitigating CO complications. In summary, this review serves as a practical guide for clinicians navigating the complexities of CO prevention and management in the evolving landscape of transcatheter aortic valve implantation, with the goal of optimizing patient outcomes and ensuring procedural success.

Integrating Structural Heart Disease Trainees within the Dynamics of the Heart Team: The Case for Multimodality Training.

Structural heart disease is a rapidly evolving field. However, training in structural heart disease is still widely variable and has not been standardized. Furthermore, integration of trainees within the heart team has not been fully defined. In this review, we discuss the components and function of the heart team, the challenges of current structural heart disease models, and possible solutions and suggestions for integrating trainees within the heart team.

Very Late Sinus of Valsalva Sequestration After Transcatheter Aortic Valve Implantation in Native Aortic Annuli.

Coronary artery obstruction caused by sinus sequestration is well described after transcatheter aortic valve implantation in failed bioprosthetic valves, which usually occurs during or shortly after the transcatheter aortic valve implantation procedure. We report the presentation, management, and outcomes of 2 cases of very late sinus sequestration in native aortic annuli, which has not been described before to our knowledge. (Level of Difficulty: Advanced.).

Immature platelet fraction (IPF) determined with an automated method predicts clopidogrel hyporesponsiveness.

The mechanisms for the variability in antiplatelet effects of clopidogrel are not elucidated entirely. Immature (reticulated) platelets may modulate the antiplatelet effects of clopidogrel but must be measured using flow cytometry. Whether new automated detection techniques yield similar results is not known. The objectives of the study to evaluate the role of immature platelets assessed by an automated method in response to the antiplatelet effects of clopidogrel. Twenty-nine healthy volunteers had platelet studies performed before and 1 week after 75 mg daily dosing of clopidogrel. Immature platelet fraction (IPF) was determined using an automated particle counter. Subjects were stratified into tertiles based on the IPF. Platelet studies included light transmission aggregometry (LTA), and vasodilator stimulated phosphoprotein phosphorylation (VASP-P) determined by platelet reactivity index (PRI). Baseline platelet aggregation responses to 2, 5 and 20 µM ADP, were similar in all three tertiles, however they were greater in the upper than in the lower tertile of immature platelets after clopidogrel in response to 5 µM ADP (54% vs. 23%, P = 0.02), with concordant trends for the other two concentrations. PRI was also greater in the upper tertile after clopidogrel (71.2% vs. 57.8%, P = 0.04). The frequency of clopidogrel hyporesponsiveness (aggregation >50% in response to 5 µM of ADP) was also higher in the upper tertile when compared to lower tertile, (60%) versus (10%) respectively (P = 0.02). [corrected]. Immature platelets measured using an automated method, are associated with impaired response to antiplatelet effects of clopidogrel.

Orbital Atherectomy of the Iliofemoral Arteries Facilitates Large-Bore Access Prior to Transfemoral Transcatheter Aortic Valve Replacement.

OBJECTIVES: To describe the use of orbital atherectomy to prepare iliofemoral vessels for large-bore access prior to transcatheter aortic valve replacement (TAVR). BACKGROUND: Transfemoral (TF)-TAVR has been shown to be at least equivalent to surgery. Nevertheless, many patients do not qualify for the TF approach due to severe iliofemoral occlusive disease. The use of an atherectomy device in order to facilitate TF-TAVR has only been reported in case reports. METHODS: We performed 1000 TAVR procedures from June 2017 to October 2019. Patient demographics, procedural characteristics, computed tomography characteristics, and short-term outcomes were recorded. Hostile access was defined as luminal size <5 mm, or <5.5 mm along with the presence of >270° calcification. The primary endpoint was the ability to successfully deliver a transcatheter valve via the intended pretreated access site. RESULTS: During the study period, 6 subjects (0.6%) required alternative access and 68 patients (6.8%) were considered to have a hostile iliofemoral anatomy that required vessel preparation prior to TAVR. Forty-eight patients (70.6%) had angioplasty only and 20 patients (29.4%) required atherectomy and angioplasty. Out of 20 patients treated with atherectomy, successful TF delivery of the valve was achieved in 19 patients (95%). There was no in-hospital mortality or stroke. There were no perforations. One subject required placement of a self-expandable stent due to severe dissection. CONCLUSION: Orbital atherectomy used for vessel preparation is a safe and very effective technique to facilitate TF-TAVR in patients with hostile peripheral anatomy.