Assessment of hemodynamic indices of conjunctival microvascular function in patients with coronary microvascular dysfunction.

OBJECTIVE: Coronary microvascular dysfunction (CMD) is a cause of ischaemia with non-obstructive coronary arteries (INOCA). It is notoriously underdiagnosed due to the need for invasive microvascular function testing. We hypothesized that systemic microvascular dysfunction could be demonstrated non-invasively in the microcirculation of the bulbar conjunctiva in patients with CMD. METHODS: Patients undergoing coronary angiography for the investigation of chest pain or dyspnoea, with physiologically insignificant epicardial disease (fractional flow reserve ≥0.80) were recruited. All patients underwent invasive coronary microvascular function testing. We compared a cohort of patients with evidence of CMD (IMR ≥25 or CFR <2.0); to a group of controls (IMR <25 and CFR ≥2.0). Conjunctival imaging was performed using a previously validated combination of a smartphone and slit-lamp biomicroscope. This technique allows measurement of vessel diameter and other indices of microvascular function by tracking erythrocyte motion. RESULTS: A total of 111 patients were included (43 CMD and 68 controls). There were no differences in baseline demographics, co-morbidities or epicardial coronary disease severity. The mean number of vessel segments analysed per patient was 21.0 ± 12.8 (3.2 ± 3.5 arterioles and 14.8 ± 10.8 venules). In the CMD cohort, significant reductions were observed in axial/cross-sectional velocity, blood flow, wall shear rate and stress. CONCLUSION: The changes in microvascular function linked to CMD can be observed non-invasively in the bulbar conjunctiva. Conjunctival vascular imaging may have utility as a non-invasive tool to both diagnose CMD and augment conventional cardiovascular risk assessment.

Redo aortic valve replacement versus valve-in-valve trans-catheter aortic valve implantation: a UK propensity-matched analysis.

This study sought to compare the morbidity and mortality of redo aortic valve replacement (redo-AVR) versus valve-in-valve trans-catheter aortic valve implantation (valve-in-valve TAVI) for patients with a failing bioprosthetic valve. A multicenter UK retrospective study of redo-AVR or valve-in-valve TAVI for patients referred for redo aortic valve intervention due to a degenerated aortic bioprosthesis. Propensity score matching was performed for confounding factors. From July 2005 to April 2021, 911 patients underwent redo-AVR and 411 patients underwent valve-in-valve TAVI. There were 125 pairs for analysis after propensity score matching. The mean age was 75.2±8.5 years. In-hospital mortality was 7.2% (n=9) for redo-AVR versus 0 for valve-in-valve TAVI, p=0.002. Surgical patients suffered more post-operative complications, including intra-aortic balloon pump support (p=0.02), early re-operation (p<0.001), arrhythmias (p<0.001), respiratory and neurological complications (p=0.02 and p=0.03) and multi-organ failure (p=0.01). The valve-in-valve TAVI group had a shorter intensive care unit and hospital stay (p<0.001 for both). However, moderate aortic regurgitation at discharge and higher post-procedural gradients were more common after valve-in-valve TAVI (p<0.001 for both). Survival probabilities in patients who were successfully discharged from the hospital were similar after valve-in-valve TAVI and redo-AVR over the 6-year follow-up (log-rank p=0.26). In elderly patients with a degenerated aortic bioprosthesis, valve-in-valve TAVI provides better early outcomes as opposed to redo-AVR, although there was no difference in mid-term survival in patients successfully discharged from the hospital.

Assessment of the conjunctival microcirculation in adult patients with cyanotic congenital heart disease compared to healthy controls.

PURPOSE: Congenital heart disease (CHD) is the most common live birth defect and a proportion of these patients have chronic hypoxia. Chronic hypoxia leads to secondary erythrocytosis resulting in microvascular dysfunction and increased thrombosis risk. The conjunctival microcirculation is easily accessible for imaging and quantitative assessment. It has not previously been studied in adult CHD patients with cyanosis (CCHD). METHODS: We assessed the conjunctival microcirculation and compared CCHD patients and matched healthy controls to determine if there were differences in measured microcirculatory parameters. We acquired images using an iPhone 6s and slit-lamp biomicroscope. Parameters measured included diameter, axial velocity, wall shear rate and blood volume flow. The axial velocity was estimated by applying the 1D + T continuous wavelet transform (CWT). Results are for all vessels as they were not sub-classified into arterioles or venules. RESULTS: 11 CCHD patients and 14 healthy controls were recruited to the study. CCHD patients were markedly more hypoxic compared to the healthy controls (84% vs 98%, p = 0.001). A total of 736 vessels (292 vs 444) were suitable for analysis. Mean microvessel diameter (D) did not significantly differ between the CCHD patients and controls (20.4 ± 2.7 µm vs 20.2 ± 2.6 µm, p = 0.86). Axial velocity (Va) was lower in the CCHD patients (0.47 ± 0.06 mm/s vs 0.53 ± 0.05 mm/s, p = 0.03). Blood volume flow (Q) was lower for CCHD patients (121 ± 30pl/s vs 145 ± 50pl/s, p = 0.65) with the greatest differences observed in vessels >22 µm diameter (216 ± 121pl/s vs 258 ± 154pl/s, p = 0.001). Wall shear rate (WSR) was significantly lower for the CCHD group (153 ± 27 s-1 vs 174 ± 22 s-1, p = 0.04). CONCLUSIONS: This iPhone and slit-lamp combination assessment of conjunctival vessels found lower axial velocity, wall shear rate and in the largest vessel group, lower blood volume flow in chronically hypoxic patients with congenital heart disease. With further study this assessment method may have utility in the evaluation of patients with chronic hypoxia.

Initial experience of a self-expanding transcatheter aortic valve with an outer pericardial wrap: The United Kingdom and Ireland Implanters' registry.

OBJECTIVES: The United Kingdom and Ireland Implanters' registry is a multicenter registry which reports on real-world experience with new transcatheter heart valves. BACKGROUND: The Evolut PRO (Medtronic, Minneapolis, MN) transcatheter aortic valve is a self-expanding transcatheter aortic valve with an outer pericardial wrap, designed to minimize paravalvular regurgitation. METHODS: Between July 2017 and December 2018, clinical, procedural, and 30-day outcome data were prospectively collected from all patients receiving the Evolut PRO valve across nine participating centers in the United Kingdom and Ireland. The primary efficacy outcome was the Valve Academic Research Consortium-2 (VARC-2)-defined endpoint of device success. The primary safety outcome was the VARC-2-defined composite endpoint of early safety at 30 days. RESULTS: A total of 317 patients underwent implantation. Mean age was 81.8 ± 6.4 years and Society of Thoracic Surgeons Predicted Risk of Mortality Score 5.5 ± 1.8%. Iliofemoral access was used in 99.1% of patients. Device success was 91.2%. Mean gradient was 7.6 ± 4.7 mmHg and effective orifice area 1.9 ± 0.7 cm2 . The incidence of moderate paravalvular regurgitation was 1.7% and there was no severe paravalvular regurgitation. A new permanent pacemaker was implanted in 17.8% of patients without a pacemaker at baseline. Early safety was demonstrated in 92.7%. At 30 days, all-cause mortality was 0.6%, stroke 3.8%, and major vascular complication 2.8%. CONCLUSIONS: Real-world experience of the Evolut PRO transcatheter aortic valve demonstrated favorable procedural success, safety, valve function, and incidence of new permanent pacemaker implantation.

Quantitative assessment of the conjunctival microcirculation using a smartphone and slit-lamp biomicroscope.

PURPOSE: The conjunctival microcirculation is a readily-accessible vascular bed for quantitative haemodynamic assessment and has been studied previously using a digital charge-coupled device (CCD). Smartphone video imaging of the conjunctiva, and haemodynamic parameter quantification, represents a novel approach. We report the feasibility of smartphone video acquisition and subsequent haemodynamic measure quantification via semi-automated means. METHODS: Using an Apple iPhone 6 s and a Topcon SL-D4 slit-lamp biomicroscope, we obtained videos of the conjunctival microcirculation in 4 fields of view per patient, for 17 low cardiovascular risk patients. After image registration and processing, we quantified the diameter, mean axial velocity, mean blood volume flow, and wall shear rate for each vessel studied. Vessels were grouped into quartiles based on their diameter i.e. group 1 (<11 µm), 2 (11-16 µm), 3 (16-22 µm) and 4 (>22 µm). RESULTS: From the 17 healthy controls (mean QRISK3 6.6%), we obtained quantifiable haemodynamics from 626 vessel segments. The mean diameter of microvessels, across all sites, was 21.1µm (range 5.8-58 µm). Mean axial velocity was 0.50mm/s (range 0.11-1mm/s) and there was a modestly positive correlation (r 0.322) seen with increasing diameter, best appreciated when comparing group 4 to the remaining groups (p < .0001). Blood volume flow (mean 145.61pl/s, range 7.05-1178.81pl/s) was strongly correlated with increasing diameter (r 0.943, p < .0001) and wall shear rate (mean 157.31 s-1, range 37.37-841.66 s-1) negatively correlated with increasing diameter (r - 0.703, p < .0001). CONCLUSIONS: We, for the first time, report the successful assessment and quantification of the conjunctival microcirculatory haemodynamics using a smartphone-based system.

Initial experience of a large, self-expanding, and fully recapturable transcatheter aortic valve: The UK & Ireland Implanters' registry.

OBJECTIVES: The UK & Ireland Implanters' registry is a multicenter registry which reports on real-world experience with novel transcatheter heart valves. BACKGROUND: The 34 mm Evolut R transcatheter aortic valve is a self-expanding and fully recapturable transcatheter aortic valve, designed to treat patients with a large aortic annulus. METHODS: Between January 2017 and April 2018, clinical, procedural and 30-day outcome data were prospectively collected from all patients receiving the 34 mm Evolut R valve across 17 participating centers in the United Kingdom and Ireland. The primary efficacy outcome was the Valve Academic Research Consortium-2(VARC-2)-defined endpoint of device success. The primary safety outcome was the VARC-2-defined composite endpoint of early safety at 30 days. RESULTS: A total of 217 patients underwent attempted implant. Mean age was 79.5 ± 8.8 years and Society of Thoracic Surgeons Predicted Risk of Mortality Score 5.2% ± 3.4%. Iliofemoral access was used in 91.2% of patients. Device success was 79.7%. Mean gradient was 7.0 ± 4.6 mmHg and effective orifice area 2.0 ± 0.6 cm2 . Paravalvular regurgitation was more than mild in 7.2%. A new permanent pacemaker was implanted in 15.7%. Early safety was demonstrated in 91.2%. At 30 days, all-cause mortality was 3.2%, stroke 3.7%, and major vascular complication 2.3%. CONCLUSIONS: Real-world experience of the 34 mm Evolut R transcatheter aortic valve demonstrated acceptable procedural success, safety, valve function, and incidence of new permanent pacemaker implantation.

An incidental finding of a right atrial myxoma with undiagnosed Ebstein anomaly: a case report.

Background: Ebstein anomaly (EA) is a rare congenital abnormality of the tricuspid valve which can lead to progressive right heart dilatation and arrhythmias. While often seen in conjunction with other congenital cardiac lesions, such as atrial septal defects, it is not normally associated with atrial myxomas. Case summary: We present a case report of an incidental finding of a right atrial myxoma in the context of undiagnosed EA, in a 16-year-old male who presented with appendicitis. Subtle cardiomegaly on routine chest X-ray prompted further investigation, which demonstrated characteristic findings of both conditions and culminated in surgical repair using the Cone procedure. At 4-month follow-up, the patient was asymptomatic, and transthoracic echocardiography demonstrated a mean gradient of 4.5 mmHg across the tricuspid valve with mild regurgitation. Discussion: The combination of EA with right-sided myxoma is exceedingly rare, and, in this case, it may be that the apical displacement of the tricuspid valve was protective against right atrioventricular obstruction. We are reminded that although subtle abnormalities on routine investigations can be of limited significance, they can also indicate more serious underlying pathology and so consideration should be given to an appropriate cascade of further investigations to yield a timely diagnosis and enable prompt treatment.

Assessment of Indices of Conjunctival Microvascular Function in Patients With and Without Obstructive Coronary Artery Disease.

BACKGROUND: Atherosclerotic heart disease often remains asymptomatic until presentation with a major adverse cardiovascular event. Primary preventive therapies improve outcomes, but conventional screening often misattributes risk. Vascular imaging can be utilised to detect atherosclerosis, but often involves ionising radiation. The conjunctiva is a readily accessible vascular network allowing non-invasive hemodynamic evaluation. AIM: To compare conjunctival microcirculatory function in patients with and without obstructive coronary artery disease. METHODS: We compared the conjunctival microcirculation of myocardial infarction patients (MI-cohort) to controls with no obstructive coronary artery disease (NO-CAD cohort). Conjunctival imaging was performed using a smartphone and slit-lamp biomicroscope combination. Microvascular indices of axial (Va) and cross-sectional (Vcs) velocity; blood flow rate (Q); and wall shear rate (WSR) were compared in all conjunctival vessels between 5 and 45 µm in diameter. RESULTS: A total of 127 patients were recruited (66 MI vs 61 NO-CAD) and 3602 conjunctival vessels analysed (2414 MI vs 1188 NO-CAD). Mean Va, Vcs and Q were significantly lower in the MI vs NO-CAD cohort (Va 0.50 ± 0.17 mm/s vs 0.55 ± 0.15 mm/s, p < 0.001; Vcs 0.35 ± 0.12 mm/s vs 0.38 ± 0.10 mm/s, p < 0.001; Q 154 ± 116 pl/s vs 198 ± 130 pl/s, p < 0.001). To correct for differences in mean vessel diameter, WSR was compared in 10-36 µm vessels (3268/3602 vessels) and was lower in the MI-cohort (134 ± 64 s-1 vs 140 ± 63 s-1, p = 0.002). CONCLUSIONS: Conjunctival microcirculatory alterations can be observed in patients with obstructive coronary artery disease. The conjunctival microvasculature merits further evaluation in cardiovascular risk screening.

Reframing Optimal Implantation of the Sapien 3 Transcatheter Heart Valve.

OBJECTIVES: To define the optimal implantation of the Sapien 3 (Edwards Lifesciences) transcatheter heart valve (THV), this study systematically analyzed the predeployment fluoroscopic THV position and correlated this to clinical outcomes. METHODS: This was an observational study of 279 patients treated with the Sapien 3 THV. Fluoroscopic imaging was used to categorize patients into low (n = 147), intermediate (n = 86), and high (n = 46) implantation zones. These zones were based on the relationship of the balloon marker and radiolucent line of the valve frame (line of lucency) to the annular plane at deployment. The primary outcome was the rate of permanent pacemaker implantation (PPI) at 30 days. The secondary outcomes were the rates of new left bundle-branch block (LBBB) in-hospital and all-cause mortality at 1 year. RESULTS: In the high, intermediate, and low groups, 30-day PPI rates were 4.3%, 8.1%, and 8.8% (P=.62); in-hospital LBBB rates were 10.9%, 26.7%, and 32.0% (P=.02); and all-cause mortality rates at 1 year were 3.1%, 7.3%, and 12.5% (P=.14), respectively. No differences were observed with respect to procedural success/complications or THV performance between the groups. CONCLUSION: This study demonstrates fewer conduction abnormalities for Sapien 3 valves positioned within a higher zone defined fluoroscopically by the line of lucency and balloon marker.

Risk of infective endocarditis after surgical and transcatheter aortic valve replacement.

OBJECTIVE: To define the incidence and risk factors for infective endocarditis (IE) following surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI). METHODS: All patients who underwent first SAVR or TAVI in England between 2007 and 2016 were identified from the NICOR databases. Hospital admissions with a primary diagnosis of IE were identified by linkage with the NHS Hospital Episode Statistics database. Approval was obtained from the NHS Research Ethics Committee. RESULTS: 2057 of 91 962 patients undergoing SAVR developed IE over a median follow-up of 53.9 months-an overall incidence of 4.81 [95% CI 4.61 to 5.03] per 1000 person-years. Correspondingly, 140 of 14 195 patients undergoing TAVI developed IE over a median follow-up of 24.5 months-an overall incidence of 3.57 [95% CI 3.00 to 4.21] per 1000 person-years. The cumulative incidence of IE at 60 months was higher after SAVR than after TAVI (2.4% [95% CI 2.3 to 2.5] vs 1.5% [95% CI 1.3 to 1.8], HR 1.60, p<0.001). Across the entire cohort, SAVR remained an independent predictor of IE after multivariable adjustment. Risk factors for IE included younger age, male sex, atrial fibrillation, and dialysis. CONCLUSIONS: IE is a rare complication of SAVR and TAVI. In our population, the incidence of IE was higher after SAVR than after TAVI.

A novel algorithm for cardiovascular screening using conjunctival microcirculatory parameters and blood biomarkers.

Microvascular haemodynamic alterations are associated with coronary artery disease (CAD). The conjunctival microcirculation can easily be assessed non-invasively. However, the microcirculation of the conjunctiva has not been previously explored in clinical algorithms aimed at identifying patients with CAD. This case-control study involved 66 patients with post-myocardial infarction and 66 gender-matched healthy controls. Haemodynamic properties of the conjunctival microcirculation were assessed with a validated iPhone and slit lamp-based imaging tool. Haemodynamic properties were extracted with semi-automated software and compared between groups. Biomarkers implicated in the development of CAD were assessed in combination with conjunctival microcirculatory parameters. The conjunctival blood vessel parameters and biomarkers were used to derive an algorithm to aid in the screening of patients for CAD. Conjunctival blood velocity measured in combination with the blood biomarkers (N-terminal pro-brain natriuretic peptide and adiponectin) had an area under receiver operator characteristic curve (AUROC) of 0.967, sensitivity 93.0%, specificity 91.5% for CAD. This study demonstrated that the novel algorithm which included a combination of conjunctival blood vessel haemodynamic properties, and blood-based biomarkers could be used as a potential screening tool for CAD and should be validated for potential utility in asymptomatic individuals.

Assessment of the conjunctival microcirculation for patients presenting with acute myocardial infarction compared to healthy controls.

Microcirculatory dysfunction occurs early in cardiovascular disease (CVD) development. Acute myocardial infarction (MI) is a late consequence of CVD. The conjunctival microcirculation is readily-accessible for quantitative assessment and has not previously been studied in MI patients. We compared the conjunctival microcirculation of acute MI patients and age/sex-matched healthy controls to determine if there were differences in microcirculatory parameters. We acquired images using an iPhone 6s and slit-lamp biomicroscope. Parameters measured included diameter, axial velocity, wall shear rate and blood volume flow. Results are for all vessels as they were not sub-classified into arterioles or venules. The conjunctival microcirculation was assessed in 56 controls and 59 inpatients with a presenting diagnosis of MI. Mean vessel diameter for the controls was 21.41 ± 7.57 µm compared to 22.32 ± 7.66 µm for the MI patients (p < 0.001). Axial velocity for the controls was 0.53 ± 0.15 mm/s compared to 0.49 ± 0.17 mm/s for the MI patients (p < 0.001). Wall shear rate was higher for controls than MI patients (162 ± 93 s-1 vs 145 ± 88 s-1, p < 0.001). Blood volume flow did not differ significantly for the controls and MI patients (153 ± 124 pl/s vs 154 ± 125 pl/s, p = 0.84). This pilot iPhone and slit-lamp assessment of the conjunctival microcirculation found lower axial velocity and wall shear rate in patients with acute MI. Further study is required to correlate these findings further and assess long-term outcomes in this patient group with a severe CVD phenotype.

Transcatheter Treatment of Residual Significant Mitral Regurgitation Following TAVR: A Multicenter Registry.

OBJECTIVES: The aim of this study was to describe baseline characteristics, and periprocedural and mid-term outcomes of patients undergoing transcatheter mitral valve interventions post-transcatheter aortic valve replacement (TAVR) and examine their clinical benefit. BACKGROUND: The optimal management of residual mitral regurgitation (MR) post-TAVR is challenging. METHODS: This was an international registry of 23 TAVR centers. RESULTS: In total, 106 of 24,178 patients (0.43%) underwent mitral interventions post-TAVR (100 staged, 6 concomitant), most commonly percutaneous edge-to-edge mitral valve repair (PMVR). The median interval post-TAVR was 164 days. Mean age was 79.5 ± 7.2 years, MR was >moderate in 97.2%, technical success was 99.1%, and 30-day device success rate was 88.7%. There were 18 periprocedural complications (16.9%) including 4 deaths. During a median follow-up of 464 days, the cumulative risk for 3-year mortality was 29.0%. MR grade and New York Heart Association (NYHA) functional class improved dramatically; at 1 year, MR was moderate or less in 90.9% of patients (mild or less in 69.1%), and 85.9% of patients were in NYHA functional class I/II. Staged PMVR was associated with lower mortality versus medical treatment (57.5% vs. 30.8%) in a propensity-matched cohort (n = 156), but this was not statistically significant (hazard ratio: 1.75; p = 0.05). CONCLUSIONS: For patients who continue to have significant MR, remain symptomatic post-TAVR, and are anatomically suitable for transcatheter interventions, these interventions are feasible, safe, and associated with significant improvement in MR grade and NYHA functional class. These results apply mainly to PMVR. A staged PMVR strategy was associated with markedly lower mortality, but this was not statistically significant. (Transcatheter Treatment for Combined Aortic and Mitral Valve Disease. The Aortic+Mitral TRAnsCatheter Valve Registry [AMTRAC]; NCT04031274).

Self-expanding CENTERA valve for the treatment of severe, symptomatic aortic stenosis.

Transcatheter aortic valve implantation (TAVI) is now an established treatment option for both high and intermediate operative risk patients with severe symptomatic aortic stenosis. The number of patients undergoing TAVI has increased over the last decade warranting continued technological improvements in transcatheter heart valve (THV) systems. The novel CENTERA self-expanding THV (Edwards Lifesciences, CA, USA) received CE approval this year. It is deliverable through a 14Fr sheath and has a unique motorized delivery system. The CENTERA-2 study results demonstrated a favorable survival rate at 30 days (99%), as well as a low need for new permanent pacemaker implantation (4.9%). 1-year outcomes reported a low incidence of >moderate paravalvular leak (0.6%) and consistently favorable THV hemodynamics making this a competitive THV for patients with severe aortic stenosis.

Forty-year-old man with dyspnoea, haemoptysis and night sweats.

CLINICAL INTRODUCTION: A 40-year-old man presented with a 1-month history of night sweats, haemoptysis, dyspnoea and weight loss. He had never smoked. Physical examination was unremarkable. He was haemodynamically stable. He was anaemic with a haemoglobin of 10 g/L and his D-dimer was elevated at 1.32 µg/mL.A 12 lead ECG showed sinus rhythm with no abnormalities. A chest radiograph (CXR) was performed (figure 1A). Transthoracic echocardiography revealed normal right ventricular size and systolic function with a step-up, distally, in pulmonary arterial (PA) velocity from 0.7 m/s to 3.2 m/s.heartjnl;105/12/919/F1F1F1Figure 1Case image panelA CT pulmonary angiogram (CTPA) (figure 1B,C) was subsequently performed. The findings of the CTPA prompted further assessment with a positron emission tomography (PET)-CT (figure 1D). QUESTION: What is the likely diagnosis? Right upper lobe bronchopneumonia.Submassive pulmonary embolism.Right upper lobe squamous cell carcinoma.Primary pulmonary artery angiosarcoma.Giant cell pulmonary arteritis.