Optimal antiplatelet and antithrombotic regimen post-transcatheter aortic valve replacement.

BACKGROUND: There are limited data regarding optimal antiplatelet/antithrombotic therapy following transcatheter aortic valve replacement (TAVR). METHODS: In this single-centre retrospective study including TAVR patients from 2012 to 2020, ischemic and bleeding outcomes were compared between antiplatelet (dual antiplatelet [DAPT] vs. single antiplatelet [SAPT]) and oral anticoagulation (OAC) groups using incidence rate, Kaplan-Meier and Cox proportional hazards analysis. RESULTS: Total 492 patients (mean age 79.7 ± 7.7 years, 53.7% males, 83.5% Caucasian) were included. There was higher incidence of 1-year death or ischemia with DAPT vs. SAPT (23.6 vs. 14.8 per 100 patient-years [PY], incidence rate ratio [IRR] 1.60, 95% confidence interval [CI] 0.97-2.68, p = .05), especially in those without coronary artery disease (23.9 vs. 10.7 per 100 PY, IRR 2.24, 95% CI 1.10-4.47, p = .017). There was significantly higher major bleeding in those on OAC vs. no OAC (15 vs. 8 per 100 PY, IRR 1.87, 95% CI 1.10-3.11, p = .016), especially late (>1-year) bleeding (10.2 vs. 3.6 per 100 PY, IRR 2.81, 95% CI 1.33-5.92, p = .004). In multivariate analysis, DAPT was an independent predictor of death or ischemia (adjusted hazard ratio [aHR] 1.41, 95% CI 1.01-1.96, p = .041). OAC was an independent predictor of major bleeding (aHR 2.32, 95% CI 1.31-4.13, p = .004). CONCLUSIONS: There is signal to harm with routine use of DAPT post-TAVR. There is higher incidence of late bleeding post-TAVR with OAC, suggesting potential role for alternate antithrombotic strategies.

Ejection Fraction Improvement Following Contemporary High-Risk Percutaneous Coronary Intervention: RESTORE EF Study Results.

Background: Despite many reports of clinical outcomes in patients undergoing high-risk percutaneous coronary intervention (HRPCI) with hemodynamic support, little is known about whether this approach improves left ventricular ejection fraction (LVEF). The purpose of the present observational study was to examine, in an ideal patient population with Impella-supported HRPCI, whether there is an impact on left ventricular function at midterm follow-up. Methods: RESTORE EF is a multicenter, retrospective analysis of a prospectively collected observational data set that aimed to assess 90-day LVEF in patients undergoing Impella-supported nonemergent HRPCI (NCT04648306), who survived with no intervening cardiac procedures prior to the primary endpoint follow-up window (90-day LVEF assessment). Secondary endpoints included change in New York Heart Association Functional Classification and Canadian Cardiovascular Society Angina Grade at the last follow-up. Results: From August 2019 to May 2021, 406 patients were enrolled at 22 US sites. Age was 70.2 â€‹â€‹± â€‹â€‹11.4 â€‹â€‹years; 26% were female. In paired assessment at 90-day follow-up, baseline LVEF improved from 35 â€‹â€‹± â€‹â€‹15% to 45 â€‹â€‹± â€‹â€‹14% (N = 251, P < .0001), with significantly greater improvement in patients with residual SYNTAX score I of 0. Percentage classified as New York Heart Association class III/IV decreased from 62% at baseline to 15% at last follow-up (P < .001), and percentage with Canadian Cardiovascular Society grade III/IV symptoms decreased from 72% to 2% (P < .0001). Conclusions: In an ideal cohort of HRPCI patients, there is a signal that hemodynamically supported HRPCI affords significant improvement in 90-day LVEF, with complete revascularization associated with greater LVEF improvement. These hypothesis-generating findings merit further assessment in large, all-comer studies and randomized trials.

Sipuleucel-T associated inflammatory cardiomyopathy: a case report and observations from a large pharmacovigilance database.

AIMS: The major cardiovascular (CV) adverse effects observed with sipuleucel-T from large multi-institutional clinical trials included thromboembolic events, myocardial infarction, and congestive heart failure in up to 0.3% of patients with CV risk factors. The incidence, outcomes, and mechanisms in real-world clinical settings of these CV adverse effects to date have not been fully elucidated. Our study identified a patient with sipuleucel-T-induced inflammatory cardiomyopathy, which led to the identification of CV adverse effects associated with sipuleucel-T from a large pharmacovigilance database and elucidation of its potential mechanisms. METHODS AND RESULTS: Using the MedDRA term 'cardiac disorders' (System Organ Class level), CV adverse events associated with sipuleucel-T versus all other drugs were reviewed from VigiBase, a large pharmacovigilance database. Disproportionality analysis was calculated by the information component (IC), a Bayesian disproportionality indicator. A positive IC025 (IC 95% lower end credibility interval) value (>0) is the traditional threshold used in statistical signal detection at the Uppsala Monitoring Centre. From VigiBase, the total number of CV adverse drug reaction reported with sipuleucel-T was 306 out of a total of 22 980 104 adverse drug reactions in VigiBase on 10/25/2020. MedDRA preferred terms levels were grouped into major CV adverse drug reaction categories where we observed significant reports of myocardial ischaemia, supraventricular tachycardia (particularly atrial fibrillation/atrial flutter), congestive heart failure, and valvular disorders. Myocardial ischemia included acute myocardial infarction (IC025 2.3) with n = 4/26 (15%) of these individual case safety reports considered fatal. Among patients with 'cardiac failure congestive' (IC025 1.5), 11 of these 43 cases (26%) were fatal with 42 (98%) of these cases considered to be solely due to sipuleucel-T. CONCLUSIONS: Patients with CV risk factors who are receiving sipuleucel-T may be at higher risk for congestive heart failure, myocardial ischemia, and supraventricular tachycardia. Electrocardiograms during weekly sipuleucel-T infusions and left ventricular function monitoring with echocardiogram should be considered in these patients. Our findings are suggestive of another rare presentation of T-cell-mediated CV toxicity with cancer immunotherapy.

Outcomes of patients with right ventricular failure requiring short-term hemodynamic support with the Impella RP device.

BACKGROUND: Right ventricular failure (RVF) after myocardial infarction, cardiotomy, or left ventricular assist device (LVAD) implantation increases morbidity and mortality. RVF also contributes to prolonged length of hospital stay and higher costs of care. The aim of this study was to evaluate the efficacy and safety of the Impella RP (Abiomed, Danvers, MA) in patients with severe RVF in these clinical settings. METHODS: This is a prospective cohort study of patients with severe RVF treated with a percutaneous right ventricular assist device (RVAD). Sixty patients with RVF refractory to medical treatment received the Impella RP device at 14 United States institutions as part of the Impella RP pre‒ and post‒market approval studies. The study population included 2 cohorts: Cohort A, patients with RVF post-(LVAD) implantation (n = 31); and Cohort B, patients with RVF post-cardiotomy, heart transplant, or myocardial infarction (n = 29). The primary end-point was survival at 30 days or hospital discharge (whichever was longer). RESULTS: Mean age of patients was 59 ± 15 years; 68% were males, 84% had a history of congestive heart failure, 44% had valvular disease, and 35% had pre-operative renal dysfunction. Patients received an average of 3.4 inotropes/vasopressors before the Impella RP implant. Patients were supported with the Impella RP for 4.0 ± 1.5 (0.5 to 14) days. Hemodynamics improved immediately after initiation of device support, with an increase in cardiac index from 1.9 ± 0.1 to 3.1 ± 0.2 liters/min/m2 (p < 0.001) and a decrease in central venous pressure from 19.0 ± 1 to 13 ± 1 mm Hg (p < 0.001). The overall survival at 30 days (or discharge) was 72%. CONCLUSIONS: To the best of our knowledge, this study represents the largest prospective study of patients with life-threatening RVF. Mechanical support with the Impella RP device in patients with RVF resulted in rapid hemodynamic improvement with reversal of shock and favorable survival.

CT based 3D printing is superior to transesophageal echocardiography for pre-procedure planning in left atrial appendage device closure.

Accurate assessment of the left atrial appendage (LAA) is important for pre-procedure planning when utilizing device closure for stroke reduction. Sizing is traditionally done with transesophageal echocardiography (TEE) but this is not always precise. Three-dimensional (3D) printing of the LAA may be more accurate. 24 patients underwent Watchman device (WD) implantation (71 ± 11 years, 42% female). All had complete 2-dimensional TEE. Fourteen also had cardiac computed tomography (CCT) with 3D printing to produce a latex model of the LAA for pre-procedure planning. Device implantation was unsuccessful in 2 cases (one with and one without a 3D model). The model correlated perfectly with implanted device size (R2 = 1; p < 0.001), while TEE-predicted size showed inferior correlation (R2 = 0.34; 95% CI 0.23-0.98, p = 0.03). Fisher's exact test showed the model better predicted final WD size than TEE (100 vs. 60%, p = 0.02). Use of the model was associated with reduced procedure time (70 ± 20 vs. 107 ± 53 min, p = 0.03), anesthesia time (134 ± 31 vs. 182 ± 61 min, p = 0.03), and fluoroscopy time (11 ± 4 vs. 20 ± 13 min, p = 0.02). Absence of peri-device leak was also more likely when the model was used (92 vs. 56%, p = 0.04). There were trends towards reduced trans-septal puncture to catheter removal time (50 ± 20 vs. 73 ± 36 min, p = 0.07), number of device deployments (1.3 ± 0.5 vs. 2.0 ± 1.2, p = 0.08), and number of devices used (1.3 ± 0.5 vs. 1.9 ± 0.9, p = 0.07). Patient specific models of the LAA improve precision in closure device sizing. Use of the printed model allowed rapid and intuitive location of the best landing zone for the device.

Pooled comparison of regadenoson versus adenosine for measuring fractional flow reserve and coronary flow in the catheterization laboratory.

BACKGROUND: Adenosine is the gold standard for augmenting coronary flow during fractional flow reserve (FFR) testing of intermediate coronary stenoses. However, intravenous infusion is time-consuming and intracoronary injection is subject to variability. Regadenoson is a newer adenosine alternative administered as a single intravenous bolus during nuclear stress testing, but its efficacy and safety during FFR testing have been evaluated only in small, single-center studies. METHODS: We pooled data from 5 academic hospitals, in which patients undergoing clinically-indicated FFR prospectively underwent comparison of intravenous adenosine infusion (140-175mcg/kg/min) versus regadenoson bolus (400mcg). Hemodynamics and symptoms with adenosine were recorded until maximal hyperemia occurred, and after returning to baseline hemodynamics, regadenoson was administered and monitoring was repeated. In a subset of patients with coronary flow data, average peak velocity (APV) at the distal flow sensor was recorded. RESULTS: Of 149 patients enrolled, mean age was 59±9years, 76% were male, and 54% underwent testing of the left anterior descending artery. Mean adenosine-FFR and regadenoson-FFR were identical (0.82±0.10) with excellent correlation of individual values (r=0.96, p<0.001) and no difference in patient-reported symptoms. Four patients (2.6%) had discrepancies between the 2 drugs for the clinical decision-making cutoff of FFR≤0.80. Coronary flow responses to adenosine and regadenoson were similar (APV at maximal hyperemia 36cm/s for both, p=0.81). CONCLUSIONS: Regadenoson single-bolus administration has comparable FFR, symptoms, and coronary flow augmentation when compared with standard intravenous adenosine infusion. With its greater ease of administration, regadenoson may be a more "user-friendly" option for invasive ischemic testing.

Global T-wave inversion on electrocardiogram: what is the differential?

Global T-wave inversion as seen on electrocardiogram is associated with a variety of pathophysiologic states, including cardiac, pulmonary, and cerebrovascular disease, and acute electrolyte disorders. Although some of these are chronic conditions, others are acute emergencies, necessitating early diagnosis and treatment. This article reviews and provides examples of possible etiologies of global T-wave inversion on electrocardiogram.

Patent foramen ovale transcatheter closure vs. medical therapy on recurrent vascular events: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: In patients with cryptogenic stroke, transcatheter (TC) closure of a patent foramen ovale (PFO) has not been shown to better prevent recurrent vascular events than medical therapy. However, randomized controlled trials (RCT) to date have included few vascular events, and lack of power has been raised as an important concern. OBJECTIVE: To conduct a systematic review and meta-analysis of existing RCT published studies assessing the recurrence of vascular events after TC PFO closure when compared to medical therapy. METHODS: Using the search terms "patent foramen ovale", "PFO", "stroke", "percutaneous closure" and "transcatheter closure", Medline, Pubmed, Embase, and Cochrane databases were reviewed from inception through April 2013, with no language restrictions. Only studies in adult humans were considered. Additional references were obtained from the bibliographies of studies reviewed. The following criteria were used for study selection: 1) randomized controlled trial, 2) subjects were adult patients with cryptogenic stroke who were randomized to TC PFO closure or medical treatment (antiplatelet therapy and/or anticoagulation), and 3) reported outcomes included cardiac death, all death, stroke, transient ischemic attack, and peripheral embolism. Methodological and descriptive data, adverse events (including raw data and risk estimates), as well as procedural success and complications were abstracted in duplicate from each study independently, and agreement was tested. We followed rigorously the recommended guidelines for reporting and conducting and assessing quality of meta-analysis of RCT. The primary endpoints pre-specified in advance were recurrent vascular events, and composite endpoint of death, and recurrent vascular events. RESULTS: Three studies were identified as meeting selection criteria. These included a total of 2,303 patients, with 1,150 patients randomized to TC PFO closure and 1,153 patients randomized to medical therapy. Mean follow-up was 3.5 years. Baseline characteristics (age, sex, and cardiovascular risk factors) were similar across studies. Intention-to-treat analyses showed a statistically significant risk reduction in stroke and/or transient ischemic attack in the TC PFO closure group when compared to medical treatment, pooled HR = 0.59, 95%CI (0.36-0.97), P = 0.04. The combined outcome of death, and vascular events, showed a borderline statistically significant benefit for TC PFO closure when compared to medical treatment, pooled HR = 0.67, 95%CI (0.44-1.00), P = 0.05 Subjects with a substantial PFO shunt seem to benefit the most with TC PFO closure, pooled HR = 0.35, 95%CI (0.12-1.03), P = 0.06, however, it did not reach statistical significance. CONCLUSION: These results suggest that in patients with cryptogenic stroke, TC PFO closure may be beneficial in reducing the risk of recurrent vascular events when compared to medical treatment. The benefit of TC PFO closure may be greater in patients with a substantial shunt.

Anakinra for myocarditis in juvenile idiopathic arthritis.

A 20-year-old pregnant woman with a history of juvenile idiopathic arthritis presented with flu-like symptoms, systemic inflammation with myocarditis, and severe cardiomyopathy. Six weeks earlier, her chronic-arthritis therapy had been changed from anakinra, an interleukin-1ß receptor antagonist, to etanercept. When she resumed taking anakinra, her condition improved dramatically, including a complete recovery of ventricular function. Myocarditis is a well-recognized complication of systemic vasculitides. This unusual case emphasizes the important pathophysiologic role of interleukin receptors in the successful treatment of myocarditis. We suggest that clinical cardiologists be aware of the therapeutic usefulness of biological agents such as anakinra in patients with rheumatic conditions.

Comparison of intravenous adenosine and intravenous regadenoson for the measurement of pressure-derived coronary fractional flow reserve.

AIMS: Defining the clinical and physiologic significance of an intermediate coronary artery stenosis is aided by measurement of fractional flow reserve (FFR). Adenosine is the most common agent used in the cardiac catheterisation laboratory for the measurement of FFR. Regadenoson, a selective adenosine receptor agonist, with fewer side effects than adenosine has been used extensively in stress testing to induce hyperaemia. We postulated that FFR measurements would be equivalent following administration of regadenoson and adenosine. METHODS AND RESULTS: Twenty patients with an angiographic intermediate coronary artery stenosis (50% to 80%) were included in the study. FFR was measured during three minutes of intravenous (IV) adenosine infusion and for five minutes after an injection of regadenoson. The mean difference between the FFR measured by IV adenosine and IV regadenoson was 0.0040 (min -0.04, max +0.04, standard deviation [SD] 0.025). There was a strong linear correlation between the FFR measured by IV adenosine and IV regadenoson (R2 linear=0.933). The FFR at maximum hyperaemia was achieved earlier using regadenoson than adenosine (59±24.5 sec vs. 93±44.5 sec, p=0.01). CONCLUSIONS: Regadenoson produces similar pressure-derived FFR compared to IV adenosine infusion.

Improvement in left ventricular systolic and diastolic performance during ranolazine treatment in patients with stable angina.

PURPOSE: Ranolazine is a novel antianginal medication that acts by ameliorating disturbed sodium and calcium homeostasis. By preventing myocyte sodium and calcium overload, ranolazine also have potential beneficial effects on myocardial function. Experimental models support this concept, as do 2 small studies in human participants receiving ranolazine intravenously. We evaluated changes in parameters of left ventricular function in stable angina patients treated with oral ranolazine. METHODS: Twenty-two participants were enrolled with Doppler echocardiography performed at baseline and a mean of 2 months after initiation of treatment. RESULTS: Global left ventricular function, as assessed by the myocardial performance index, was significantly improved on drug therapy (P < .0001). This was due to improvement in both diastolic and systolic parameters. Of 21 patients, 17 reported less angina and 8 patients reported an increase in activity level. CONCLUSIONS: We report improved parameters of left ventricular function in response to ranolazine as used in the clinical setting.

Distribution of left ventricular ejection fraction in angina patients with severe coronary artery disease not amenable to revascularization.

BACKGROUND: As the number of angina patients with severe coronary artery disease not amenable to revascularization increases, new therapies will be developed. How patients with depressed compared to normal left ventricular ejection fraction (LVEF) will respond to new therapies may differ. HYPOTHESIS: We conducted a retrospective chart review to determine the distribution of LVEF in angina patients with severe coronary artery disease (three-vessel disease with >50% stenosis major epicardial vessels or >50% stenosis left main) not amenable to revascularization. METHODS: Patients underwent cardiac catheterization between 2004 and 2009. LVEF, measured by echocardiography, nuclear-gated imaging or radioventriculography within 6 months of catheterization, was recorded. Demographics, symptoms, risk factors, past myocardial infarction, catheterization results, medications, and the Duke Coronary Artery Jeopardy Score were recorded. RESULTS: Eight thousand six hundred and ninety-nine patient charts were reviewed; 124 met criteria. There was a continuous, and not bimodal, distribution of LVEF. Fifty-eight patients (47%) in the normal LVEF group were compared to 66 patients (53%) in the abnormal LVEF group (<50%). The two groups were statistically different only with respect to shortness of breath as a presenting symptom and diagnosis of congestive heart failure during index hospitalization. Follow-up mortality was high and did not differ between LVEF groups (35% vs. 34%). CONCLUSION: There is a wide distribution of LVEF among angina patients not amenable to revascularization. A novel finding of this study showed that mortality was high regardless of LVEF. As new therapies for angina are developed, attention will need to be paid to how such therapies affect these two patient groups.