Aortic Valve Calcium Score Is Associated With Acute Stroke in Transcatheter Aortic Valve Replacement Patients.

Background: Transcatheter aortic valve replacement (TAVR) is the treatment of choice for patients with severe aortic stenosis who are at a moderate or higher surgical risk. Stroke is a recognised and serious complication of TAVR, and it is important to identify patients at higher stroke risk. This study aims to discover if aortic valve calcium score calculated from pre-TAVR computed tomography is associated with acute stroke in TAVR patients. Methods: We conducted a retrospective, observational cohort study of 433 consecutive patients undergoing TAVR between January 2017 and December 2019 at the Hammersmith Hospital. Results: This cohort had a median age of 83 years (interquartile range, 78-87), and 52.7% were male. Fifty-two patients (12.0%) had a history of previous stroke or transient ischemic attack. Median aortic valve calcium score was 2145 (interquartile range, 1427-3247) Agatston units. Twenty-two patients had a stroke up to the time of discharge (5.1%). In a logistic regression model, aortic valve calcium score was significantly associated with acute stroke (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.01-1.53; P = .02). Acute stroke was also significantly associated with peripheral arterial disease (OR, 4.32; 95% CI, 1.65-10.65; P = .0018) and a longer procedure time (OR, 1.01; 95% CI, 1.00-1.02; P = .0006). Conclusions: Aortic valve calcium score from pre-TAVR computed tomography is an independent risk factor for acute stroke in the TAVR population. This is an additional clinical value of the pre-TAVR aortic valve calcium score and should be considered when discussing periprocedural stroke risk.

Balloon Nudge Technique: A Touch to Nonsteerable Valves.

Transfemoral transcatheter aortic valve replacement is an effective treatment for severe aortic stenosis with a high rate of procedural success with the current devices. However, anatomic factors and device limitations may increase technical difficulty. We describe the balloon nudge technique, a novel technique that improves coaxial alignment while crossing the aortic valve. (Level of Difficulty: Advanced.).

Management of Acute Coronary Syndromes During the Coronavirus Disease 2019 Pandemic: Deviations from Guidelines and Pragmatic Considerations for Patients and Healthcare Workers.

Coronavirus disease 2019 (COVID-19) is forcing cardiology departments to rapidly adapt existing clinical guidelines to a new reality and this is especially the case for acute coronary syndrome pathways. In this focused review, the authors discuss how COVID-19 is affecting acute cardiology care and propose pragmatic guideline modifications for the diagnosis and management of acute coronary syndrome patients, particularly around the appropriateness of invasive strategies as well as length of hospital stay. The authors also discuss the use of personal protective equipment for healthcare workers in cardiology. Based on shared global experiences and growing peer-reviewed literature, it is possible to put in place modified acute coronary syndrome treatment pathways to offer safe pragmatic decisions to patients and staff.

Comparison of the self-expanding Evolut-PRO transcatheter aortic valve to its predecessor Evolut-R in the real world multicenter ATLAS registry.

BACKGROUND: The Evolut PRO self-expanding transcatheter aortic valve has been designed to feature an outer pericardial wrap that aims to reduce paravalvular regurgitation (PVR) rates. Medium-term clinical outcomes, compared to its predecessor Evolut R, in a real-world setting, have not been investigated. The aim of the present study was to compare the two valves with regards to peri-procedural complications, early outcomes and mid-term survival. METHODS: Consecutive patients, undergoing TAVI with either the Evolut PRO or Evolut R device, from the multicenter ATLAS registry were retrospectively studied. Outcomes studied included periprocedural complications, PVR at discharge, need for new pacemaker implantation and Kaplan-Meier estimated 1-year all-cause mortality. RESULTS: Analysis included 673 patients (498 treated with Evolut R and 175 treated with Evolut PRO). At least moderate PVR was numerically lower amongst patients treated with Evolut PRO (7.4% vs 3.8% for Evolut R and Evolut PRO respectively, p = .108). Rates of new permanent pacemaker (PPM) implantation (21.1% vs. 11.9%, p = .023), and bail-out valve-in-valve (2.4% vs. 0%, p = .049) were significantly lower amongst the Evolut PRO group. No differences were demonstrated regarding bleeding, stroke or acute kidney injury. One-year Kaplan-Meier estimated survival was similar between groups (93% for Evolut R vs. 91.2% for Evolut PRO, plog-rank = 0.806). CONCLUSIONS: The Evolut PRO self-expanding valve demonstrates similar mid-term survival rates and numerically, yet not significant, lower incidence of PVR compared to its predecessor. Interestingly this new generation valve is associated with a significantly reduced rate for new PPM implantation. Future studies are required to confirm this finding.

Left ventricular speckle tracking echocardiographic evaluation before and after TAVI.

AIMS: To assess left ventricular (LV) function before and after transcatheter aortic valve implantation (TAVI) using conventional echocardiographic parameters and global longitudinal LV strain (GLS) and compare outcomes between Edwards S3 and Evolut R valves. METHODS AND RESULTS: Data were collected for consecutive patients undergoing TAVI at Hammersmith hospital between 2015 and 2018. Of the 303 patients, those with coronary artery disease and atrial fibrillation were excluded leading to a total of 85 patients, which constituted our study group. The mean follow-up was 49 ± 39 days. In total, 60% of patients were treated with Edwards S3 and 40% Evolut R. TAVI resulted in an early improvement of GLS (-13.96 to -15.25%, P = 0.01) but not ejection fraction (EF) (47.6 to 50.1%, P = 0.09). LV mass also improved, especially in patients with marked baseline LV hypertrophy (P < 0.001). There were no appreciable differences of LV function improvement and overall LV remodelling after TAVI between the two types of valves used (P = 0.14). CONCLUSIONS: TAVI results in reverse remodelling and improvement of GLS, especially in patients with impaired baseline LV function. There were no differences in the extent of LV function improvement between Edwards S3 and Evolut R valves but there was a greater incidence of aortic regurgitation with Evolut R.

Facilitating right-sided axillary artery access for transcatheter aortic valve replacement using the Edwards Sapien 3 and ultra valves: Technical considerations.

Trans-Axillary Transcatheter Aortic Valve Replacement (TAVR) has become established as the safest arterial approach when femoral arterial anatomy is unfavorable. Although a left sided axillary approach is generally preferred, patient specific factors may require use of the right axillary artery. In this case series we describe procedural modifications that are required to overcome the challenge of restricted space in the ascending aorta for in situ valve preparation of balloon-expandable valve systems when a right sided trans-Axillary approach is taken. These steps permit implantation of both the Edwards LifeSciences Sapien 3 and Ultra prostheses via the right trans-Axillary approach, allowing patients a greater range of valve options when this arterial route is required for TAVR.

Determining the Predominant Lesion in Patients With Severe Aortic Stenosis and Coronary Stenoses: A Multicenter Study Using Intracoronary Pressure and Flow.

BACKGROUND: Patients with severe aortic stenosis (AS) often have coronary artery disease. Both the aortic valve and the coronary disease influence the blood flow to the myocardium and its ability to respond to stress; leading to exertional symptoms. In this study, we aim to quantify the effect of severe AS on the coronary microcirculation and determine if this is influenced by any concomitant coronary disease. We then compare this to the effect of coronary stenoses on the coronary microcirculation. METHODS: Group 1: 55 patients with severe AS and intermediate coronary stenoses treated with transcatheter aortic valve implantation (TAVI) were included. Group 2: 85 patients with intermediate coronary stenoses and no AS treated with percutaneous coronary intervention were included. Coronary pressure and flow were measured at rest and during hyperemia in both groups, before and after TAVI (group 1) and before and after percutaneous coronary intervention (group 2). RESULTS: Microvascular resistance over the wave-free period of diastole increased significantly post-TAVI (pre-TAVI, 2.71±1.4 mm Hg·cm·s-1 versus post-TAVI 3.04±1.6 mm Hg·cm·s-1 [P=0.03]). Microvascular reserve over the wave-free period of diastole significantly improved post-TAVI (pre-TAVI 1.88±1.0 versus post-TAVI 2.09±0.8 [P=0.003]); this was independent of the severity of the underlying coronary stenosis. The change in microvascular resistance post-TAVI was equivalent to that produced by stenting a coronary lesion with an instantaneous wave-free ratio of ≤0.74. CONCLUSIONS: TAVI improves microcirculatory function regardless of the severity of underlying coronary disease. TAVI for severe AS produces a coronary hemodynamic improvement equivalent to the hemodynamic benefit of stenting coronary stenoses with instantaneous wave-free ratio values <0.74. Future trials of physiology-guided revascularization in severe AS may consider using this value to guide treatment of concomitant coronary artery disease.

Coronary Hemodynamics in Patients With Severe Aortic Stenosis and Coronary Artery Disease Undergoing Transcatheter Aortic Valve Replacement: Implications for Clinical Indices of Coronary Stenosis Severity.

OBJECTIVES: In this study, a systematic analysis was conducted of phasic intracoronary pressure and flow velocity in patients with severe aortic stenosis (AS) and coronary artery disease, undergoing transcatheter aortic valve replacement (TAVR), to determine how AS affects: 1) phasic coronary flow; 2) hyperemic coronary flow; and 3) the most common clinically used indices of coronary stenosis severity, instantaneous wave-free ratio and fractional flow reserve. BACKGROUND: A significant proportion of patients with severe aortic stenosis (AS) have concomitant coronary artery disease. The effect of the valve on coronary pressure, flow, and the established invasive clinical indices of stenosis severity have not been studied. METHODS: Twenty-eight patients (30 lesions, 50.0% men, mean age 82.1 ± 6.5 years) with severe AS and coronary artery disease were included. Intracoronary pressure and flow assessments were performed at rest and during hyperemia immediately before and after TAVR. RESULTS: Flow during the wave-free period of diastole did not change post-TAVR (29.78 ± 14.9 cm/s vs. 30.81 ± 19.6 cm/s; p = 0.64). Whole-cycle hyperemic flow increased significantly post-TAVR (33.44 ± 13.4 cm/s pre-TAVR vs. 40.33 ± 17.4 cm/s post-TAVR; p = 0.006); this was secondary to significant increases in systolic hyperemic flow post-TAVR (27.67 ± 12.1 cm/s pre-TAVR vs. 34.15 ± 17.5 cm/s post-TAVR; p = 0.02). Instantaneous wave-free ratio values did not change post-TAVR (0.88 ± 0.09 pre-TAVR vs. 0.88 ± 0.09 post-TAVR; p = 0.73), whereas fractional flow reserve decreased significantly post-TAVR (0.87 ± 0.08 pre-TAVR vs. 0.85 ± 0.09 post-TAVR; p = 0.001). CONCLUSIONS: Systolic and hyperemic coronary flow increased significantly post-TAVR; consequently, hyperemic indices that include systole underestimated coronary stenosis severity in patients with severe AS. Flow during the wave-free period of diastole did not change post-TAVR, suggesting that indices calculated during this period are not vulnerable to the confounding effect of the stenotic aortic valve.

Attenuation of reflected waves in man during retrograde propagation from femoral artery to proximal aorta.

BACKGROUND: Wave reflection may be an important influence on blood pressure, but the extent to which reflections undergo attenuation during retrograde propagation has not been studied. We quantified retrograde transmission of a reflected wave created by occlusion of the left femoral artery in man. METHODS: 20 subjects (age 31-83 years; 14 male) underwent invasive measurement of pressure and flow velocity with a sensor-tipped intra-arterial wire at multiple locations distal to the proximal aorta before, during and following occlusion of the left femoral artery by thigh cuff inflation. A numerical model of the circulation was also used to predict reflected wave transmission. Wave reflection was measured as the ratio of backward to forward wave energy (WRI) and the ratio of peak backward to forward pressure (Pb/Pf). RESULTS: Cuff inflation caused a marked reflection which was largest at 5-10 cm from the cuff (change (Δ) in WRI=0.50 (95% CI 0.38, 0.62); p<0.001, ΔPb/Pf=0.23 (0.18-0.29); p<0.001). The magnitude of the cuff-induced reflection decreased progressively at more proximal locations and was barely discernible at sites>40 cm from the cuff including in the proximal aorta. Numerical modelling gave similar predictions to those observed experimentally. CONCLUSIONS: Reflections due to femoral artery occlusion are markedly attenuated by the time they reach the proximal aorta. This is due to impedance mismatches of bifurcations traversed in the backward direction. This degree of attenuation is inconsistent with the idea of a large discrete reflected wave arising from the lower limb and propagating back into the aorta.

Improvement in coronary haemodynamics after percutaneous coronary intervention: assessment using instantaneous wave-free ratio.

OBJECTIVE: To determine whether the instantaneous wave-free ratio (iFR) can detect improvement in stenosis significance after percutaneous coronary intervention (PCI) and compare this with fractional flow reserve (FFR) and whole cycle Pd/Pa. DESIGN: A prospective observational study was undertaken in elective patients scheduled for PCI with FFR ≤ 0.80. Intracoronary pressures were measured at rest and during adenosine-mediated vasodilatation, before and after PCI. iFR, Pd/Pa and FFR values were calculated using the validated fully automated algorithms. SETTING: Coronary catheter laboratories in two UK centres and one in the USA. PATIENTS: 120 coronary stenoses in 112 patients were assessed. The mean age was 63 ± 10 years, while 84% were male; 39% smokers; 33% with diabetes. Mean diameter stenosis was 68 ± 16% by quantitative coronary angiography. RESULTS: Pre-PCI, mean FFR was 0.66 ± 0.14, mean iFR was 0.75 ± 0.21 and mean Pd/Pa 0.83 ± 0.16. PCI increased all indices significantly (FFR 0.89 ± 0.07, p<0.001; iFR 0.94 ± 0.05, p<0.001; Pd/Pa 0.96 ± 0.04, p<0.001). The change in iFR after intervention (0.20 ± 0.21) was similar to ΔFFR 0.22 ± 0.15 (p=0.25). ΔFFR and ΔiFR were significantly larger than resting ΔPd/Pa (0.13 ± 0.16, both p<0.001). Similar incremental changes occurred in patients with a higher prevalence of risk factors for microcirculatory disease such as diabetes and hypertension. CONCLUSIONS: iFR and FFR detect the changes in coronary haemodynamics elicited by PCI. FFR and iFR have a significantly larger dynamic range than resting Pd/Pa. iFR might be used to objectively document improvement in coronary haemodynamics following PCI in a similar manner to FFR.

Diagnostic classification of the instantaneous wave-free ratio is equivalent to fractional flow reserve and is not improved with adenosine administration. Results of CLARIFY (Classification Accuracy of Pressure-Only Ratios Against Indices Using Flow Study).

OBJECTIVES: This study sought to determine if adenosine administration is required for the pressure-only assessment of coronary stenoses. BACKGROUND: The instantaneous wave-free ratio (iFR) is a vasodilator-free pressure-only measure of the hemodynamic severity of a coronary stenosis comparable to fractional flow reserve (FFR) in diagnostic categorization. In this study, we used hyperemic stenosis resistance (HSR), a combined pressure-and-flow index, as an arbiter to determine when iFR and FFR disagree which index is most representative of the hemodynamic significance of the stenosis. We then test whether administering adenosine significantly improves diagnostic performance of iFR. METHODS: In 51 vessels, intracoronary pressure and flow velocity was measured distal to the stenosis at rest and during adenosine-mediated hyperemia. The iFR (at rest and during adenosine administration [iFRa]), FFR, HSR, baseline, and hyperemic microvascular resistance were calculated using automated algorithms. RESULTS: When iFR and FFR disagreed (4 cases, or 7.7% of the study population), HSR agreed with iFR in 50% of cases and with FFR in 50% of cases. Differences in magnitude of microvascular resistance did not influence diagnostic categorization; iFR, iFRa, and FFR had equally good diagnostic agreement with HSR (receiver-operating characteristic area under the curve 0.93 iFR vs. 0.94 iFRa and 0.96 FFR, p = 0.48). CONCLUSIONS: iFR and FFR had equivalent agreement with classification of coronary stenosis severity by HSR. Further reduction in resistance by the administration of adenosine did not improve diagnostic categorization, indicating that iFR can be used as an adenosine-free alternative to FFR.

Classification performance of instantaneous wave-free ratio (iFR) and fractional flow reserve in a clinical population of intermediate coronary stenoses: results of the ADVISE registry.

AIMS: To evaluate the classification agreement between instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) in patients with angiographic intermediate coronary stenoses. METHODS AND RESULTS: Three hundred and twelve patients (339 stenoses) with angiographically intermediate stenoses were included in this international clinical registry. The iFR was calculated using fully automated algorithms. The receiver operating characteristic (ROC) curve was used to identify the iFR optimal cut-point corresponding to FFR 0.8. The classification agreement of coronary stenoses as significant or non-significant was established between iFR and FFR and between repeated FFR measurements for each 0.05 quantile of FFR values, from 0.2 to 1. Close agreement was observed between iFR and FFR (area under ROC curve= 86%). The optimal iFR cut-off (for an FFR of 0.80) was 0.89. After adjustment for the intrinsic variability of FFR, the classification agreement (accuracy) between iFR and FFR was 94%. Amongst the stenoses classified as non-significant by iFR (>0.89) and as significant by FFR (≤0.8), 81% had associated FFR values located within the FFR "grey-zone" (0.75-0.8) and 41% within the 0.79-0.80 FFR range. CONCLUSIONS: In a population of intermediate coronary stenoses, the classification agreement between iFR and FFR is excellent and similar to that of repeated FFR measurements in the same sample. Vasodilator-independent assessment of intermediate stenosis seems applicable and may foster adoption of coronary physiology in the catheterisation laboratory.

Why does primary angioplasty not work in registries? Quantifying the susceptibility of real-world comparative effectiveness data to allocation bias.

BACKGROUND: Meta-analysis of registries (comparative effectiveness research) shows that primary angioplasty and fibrinolysis have equivalent real-world survival. Yet, randomized, controlled trials consistently find primary angioplasty superior. Can unequal allocation of higher-risk patients in registries have masked primary angioplasty benefit? METHODS AND RESULTS: First, we constructed a model to demonstrate the potential effect of allocation bias. We then analyzed published registries (55022 patients) for allocation of higher-risk patients (Killip class ≥1) to determine whether the choice of reperfusion therapy was affected by the risk level of the patient. Meta-regression was used to examine the relationship between differences in allocation of high-risk patient to primary angioplasty or fibrinolysis and mortality. Initial modeling suggested that registry outcomes are sensitive to allocation bias of high-risk patients. Across the registries, the therapy receiving excess high-risk patients had worse mortality. Unequal distribution of high-risk status accounted for most of the between-registry variance (adjusted R(2)(meta)=83.1%). Accounting for differential allocation of higher-risk patients, primary angioplasty gave 22% lower mortality (odds ratio, 0.78; 95% confidence interval, 0.64-0.97; P=0.029). We derive a formula, called the number needed to abolish, highlighting situations in which comparative effectiveness studies are particularly vulnerable to this bias. CONCLUSIONS: In ST-segment elevation myocardial infarction, clinicians' preference for management of a few high-risk patients can shift mortality substantially. Comparative effectiveness research in any disease is vulnerable to this, especially diseases with an immediately identifiable high-risk subgroup that clinicians prefer to allocate to 1 therapy. For this reason, preliminary indications from registry-based comparative effectiveness research should be definitively tested by randomized, controlled trials.

Severe cardiac failure due to rapidly progressive rheumatoid arthritis-associated valvulopathy.

Cardiac failure due to rapidly progressive valve disease is a rare complication of rheumatoid arthritis (RA) that can be challenging to manage. A patient with severe heart failure secondary to RA who, after failing to respond to medical therapy, underwent high-risk valve surgery and did remarkably well, with dramatic symptomatic improvement and essentially normalised left ventricular size and function as seen on follow-up echocardiography.

Attenuation of wave reflection by wave entrapment creates a "horizon effect" in the human aorta.

Wave reflection is thought to be important in the augmentation of blood pressure. However, identification of distal reflections sites remains unclear. One possible explanation for this is that wave reflection is predominately determined by an amalgamation of multiple proximal small reflections rather than large discrete reflections originating from the distal peripheries. In 19 subjects (age, 35-73 years), sensor-tipped intra-arterial wires were used to measure pressure and Doppler velocity at 10-cm intervals along the aorta, starting at the aortic root. Incident and reflected waves were identified and timings and magnitudes quantified using wave intensity analysis. Mean wave speed increased along the length of the aorta (proximal, 6.8±0.9 m/s; distal, 10.7±1.5 m/s). The incident wave was tracked moving along the aorta, taking 55±4 ms to travel from the aortic root to the distal aorta. However, the timing to the refection site distance did not differ between proximal and distal aortic measurement sites (proximal aorta, 48±5 ms versus distal aorta, 42±4 ms; P=0.3). We performed a second analysis using aortic waveforms in a nonlinear model of pulse-wave propagation. This demonstrated very similar results to those observed in vivo and also an exponential attenuation in reflection magnitude. There is no single dominant refection site in or near the distal aorta. Rather, there are multiple reflection sites along the aorta, for which the contributions are attenuated with distance. We hypothesize that rereflection of reflected waves leads to wave entrapment, preventing distal waves being seen in the proximal aorta.

Arterial pulse wave dynamics after percutaneous aortic valve replacement: fall in coronary diastolic suction with increasing heart rate as a basis for angina symptoms in aortic stenosis.

BACKGROUND: Aortic stenosis causes angina despite unobstructed arteries. Measurement of conventional coronary hemodynamic parameters in patients undergoing valvular surgery has failed to explain these symptoms. With the advent of percutaneous aortic valve replacement (PAVR) and developments in coronary pulse wave analysis, it is now possible to instantaneously abolish the valvular stenosis and to measure the resulting changes in waves that direct coronary flow. METHODS AND RESULTS: Intracoronary pressure and flow velocity were measured immediately before and after PAVR in 11 patients with unobstructed coronary arteries. Using coronary pulse wave analysis, we calculated the intracoronary diastolic suction wave (the principal accelerator of coronary blood flow). To test physiological reserve to increased myocardial demand, we measured at resting heart rate and during pacing at 90 and 120 bpm. Before PAVR, the basal myocardial suction wave intensity was 1.9±0.3×10(-5) W · m(-2) · s(-2), and this increased in magnitude with increasing severity of aortic stenosis (r=0.59, P=0.05). This wave decreased markedly with increasing heart rate (ß coefficient=-0.16×10(-4) W · m(-2) · s(-2); P<0.001). After PAVR, despite a fall in basal suction wave (1.9±0.3 versus 1.1±0.1×10(-5) W · m(-2) · s(-2); P=0.02), there was an immediate improvement in coronary physiological reserve with increasing heart rate (ß coefficient=0.9×10(-3) W · m(-2) · s(-2); P=0.014). CONCLUSIONS: In aortic stenosis, the coronary physiological reserve is impaired. Instead of increasing when heart rate rises, the coronary diastolic suction wave decreases. Immediately after PAVR, physiological reserve returns to a normal positive pattern. This may explain how aortic stenosis can induce anginal symptoms and their prompt relief after PAVR. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01118442.