Hemodynamic and Mid-Term Outcomes for Transcatheter Aortic Valve Replacement in Degenerated Internally Stented Valves.

BACKGROUND: Valve-in-valve (ViV) transcatheter aortic valve replacement is indicated in patients undergoing repeat intervention for degenerative aortic valve bioprostheses. Patients with internally stented valves (ie, Mitroflow and Trifecta) are at high risk for coronary artery obstruction during ViV procedures because of valve design, as the leaflets are mounted outside the valve stent. OBJECTIVES: The aim of this study was to compare the hemodynamic and clinical outcomes of transcatheter aortic valve replacement within internally stented valves (ViV-IS) vs other surgical valves (ViV-OS). METHODS: Baseline characteristics, hemodynamic parameters, and clinical outcomes of patients who underwent ViV-IS were retrospectively collected and compared with those of patients who underwent ViV-OS. RESULTS: A total of 250 patients (65% men, median Society of Thoracic Surgeons score 4.4% [IQR: 2.2%-8.4%]) were included. Seventy-one patients (28%) underwent ViV-IS, and 179 (72%) patients underwent ViV-OS. Patients who underwent ViV-OS had better periprocedural hemodynamic status compared with those who underwent ViV-IS (median mean gradient 6 [IQR: 2-13] vs 12 [IQR: 6-16]; P < 0.001). This was not significantly different when both groups were matched on the basis of age, sex, and valve internal diameter size (median mean gradient: 18 [IQR: 13-25] for ViV-OS vs 18 [IQR: 11-24] for ViV-IS; P = 0.36). Coronary protection for potential occlusion was performed more in ViV-IS vs ViV-OS pr (79% vs 6%, respectively; P < 0.001). Patients who underwent ViV-IS had a higher risk for coronary occlusion, requiring stent deployment, compared with those who underwent ViV-OS (54% vs 3%, respectively; P < 0.001. There was no difference in mortality at 3 years between the 2 groups (P = 0.59). CONCLUSIONS: Patients who underwent ViV-IS had a very high incidence of coronary compromise that can be safely and effectively treated. In the setting of a systematic coronary protection strategy, ViV-OS and ViV-IS provide similar mid-term outcome, and periprocedural hemodynamic status (following adjustment for age, sex, and true internal diameter).

Two-year outcomes from the MitrAl ValvE RepaIr Clinical (MAVERIC) trial: a novel percutaneous treatment of functional mitral regurgitation.

AIMS: We report the 2-year outcomes of the MitrAl ValvE RepaIr Clinical (MAVERIC) trial. Functional mitral regurgitation (FMR) is associated with poor outcomes for which there remains an unmet clinical need. ARTO is a transcatheter annular reduction device for the treatment of FMR and an emerging alternative for patients at high surgical risk. The MAVERIC trial was designed to evaluate the safety and performance of the ARTO system in FMR and heart failure (HF). METHODS AND RESULTS: MAVERIC is an international multicentre, prospective, single arm study enrolling patients with FMR grade ≥ 2, New York Heart Association (NYHA) class ≥II symptoms despite maximal medical therapy. Patients were excluded if they had significant structural mitral valve abnormality or life expectancy <1 year. The primary outcome measures were a composite safety outcome and efficacy defined as mitral regurgitation (MR) reduction 30 days post-procedure. Secondary outcome measures included safety, change in MR grade, NYHA class and hospitalization for HF at 2 years. Forty-five patients were enrolled. The composite safety outcome was met (2/45 adverse events at 30 days) and no device-related deaths occurred at 2-year follow-up. A sustained reduction in MR [grade < 2: 21/31 (68%) vs. 31/31(0%); P < 0.0001], left ventricular end-diastolic volume index (90.0 ± 30 vs. 106 ± 26 mL/m2 ; P = 0.004) and anteroposterior diameter (35.5 ± 4.7 vs. 41.4 ± 4.6 mm; P < 0.0001) was seen at 2 years compared to baseline. Progressive symptomatic improvement [NYHA class ≤II: 27/34 (80%) vs. 12/34 (36%); P < 0.0001] and a reduction in HF hospitalizations (19.8% 2 years post vs. 52.3% 2 years prior; P < 0.001) were seen at 2 years compared to baseline. CONCLUSIONS: The ARTO system is a safe and effective treatment for FMR with reductions in left ventricular end-diastolic volumes sustained to 2 years.

Usefulness of Computed Tomography to Predict Mitral Stenosis After Transcatheter Mitral Valve Edge-to-Edge Repair.

Multidetector computed tomography (MDCT) can provide valuable information for preprocedural planning of transcatheter mitral valve interventions. However, no data exists on pre-MDCT parameters predicting high transmitral pressure gradient (TMPG) post-MitraClip procedure. We analyzed the preprocedural MDCTs of 156 consecutive patients with mitral regurgitation undergoing MitraClip implantation at our institution. The mean TMPG was assessed by periprocedural transesophageal and pre-discharge transthoracic echocardiography. MDCT-derived mitral annulus area (MAA), anterior-posterior (AP) and medial-lateral (ML) mitral annulus diameters, and mitral valve orifice area (MVOA) were smaller in patients with mean TMPG ≥5 mmHg than those with mean TMPG <5 mmHg after 1-or 2-clip implantation. Small MAA, AP and ML diameters, and MVOA were moderately correlated with high TMPG post-MitraClip, in which MAA and MVOA had the highest degree of correlation after 1-clip (r = -0.46 both), whereas MAA and ML had the strongest degree of correlation after 2-clip (r = -0.39 both) and at discharge (r = -0.38 both). From the receiver-operating-characteristic curve analyses, no significant differences in the area under the curve were observed among these MDCT parameters for low TMPG after MitraClip implantation, except for those between MAA and AP diameter at discharge (p=0.026). For optimal cutoff values, MAA ≥1100 and ≥1300 mm2 had positive predictive values of 89% and 91%, while both MAA ≥750 and ≥900 mm2 had negative predictive values of 100%, for mean TMPG <5 mmHg after 1-and 2-clip implantation, respectively. In conclusion, in patients undergoing the MitraClip procedure, preprocedural MDCT parameters are useful to predict postprocedural mitral stenosis.

Impact of coronary artery disease on contractile function and ventricular-arterial coupling during exercise: Simultaneous assessment of left-ventricular pressure-volume and coronary pressure and flow during cardiac catheterization.

Coronary artery disease (CAD) can adversely affect left ventricular (LV) performance during exercise by impairment of contractile function in the presence of increasing afterload. By performing invasive measures of LV pressure-volume and coronary pressure and flow during exercise, we sought to accurately measure this with comparison to the control group. Sixteen patients, with CCS class >II angina and CAD underwent invasive simultaneous measurement of left ventricular pressure-volume and coronary pressure and flow velocity during cardiac catheterization. Measurements performed at rest were compared with peak exercise using bicycle ergometry. The LV contractile function was measured invasively using the end-systolic pressure-volume relationship, a load independent marker of contractile function (Ees). Vascular afterload forces were derived from the ratio of LV end-systolic pressure to stroke volume to generate arterial elastance (Ea). These were combined to assess cardiovascular performance (ventricular-arterial [VA] coupling ratio [Ea/Ees]). Eleven patients demonstrated flow-limiting (FL) CAD (hyperemic Pd/Pa <0.80; ST-segment depression on exercise); five patients without flow-limiting (NFL) CAD served as the control group. Exercise in the presence of FL CAD was associated impairment of Ees, increased Ea, and deterioration of VA coupling. In the control cohort, exercise was associated with increased Ees and improved VA coupling. The backward compression wave energy directly correlated with the magnitude contraction as measured by dP/dTmax (r = 0.88, p = 0.004). This study demonstrates that in the presence of flow-limiting CAD, exercise to maximal effort can lead to impairment of LV contractile function and a deterioration in VA coupling compared to a control cohort.

Physiological Impact of Afterload Reduction on Cardiac Mechanics and Coronary Hemodynamics Following Isosorbide Dinitrate Administration in Ischemic Heart Disease.

Understanding the cardiac-coronary interaction is fundamental to developing treatment strategies for ischemic heart disease. We sought to examine the impact of afterload reduction following isosorbide dinitrate (ISDN) administration on LV properties and coronary hemodynamics to further our understanding of the cardiac-coronary interaction. Novel methodology enabled real-time simultaneous acquisition and analysis of coronary and LV hemodynamics in vivo using coronary pressure-flow wires (used to derive coronary wave energies) and LV pressure-volume loop assessment. ISDN administration resulted in afterload reduction, reduced myocardial demand, and increased mechanical efficiency (all P<0.01). Correlations were demonstrated between the forward compression wave (FCW) and arterial elastance (r=0.6) following ISDN. In the presence of minimal microvascular resistance, coronary blood flow velocity exhibited an inverse relationship with LV elastance. In summary this study demonstrated a reduction in myocardial demand with ISDN, an inverse relationship between coronary blood flow velocity and LV contraction-relaxation and a direct correlation between FCW and arterial elastance. The pressure volume-loop and corresponding parameters b The pressure volume loop before (solid line) and after (broken line) Isosorbide dintrate.

Transcatheter Aortic Valve Replacement With the LOTUS Edge System: Early European Experience.

OBJECTIVES: The aim of this study was to evaluate the short-term safety and efficacy of transcatheter aortic valve replacement (TAVR) with the LOTUS Edge system. BACKGROUND: The LOTUS Edge system was commercially re-released in April 2019. The authors report the first European experience with this device. METHODS: A multicenter, single-arm, retrospective registry was initiated to evaluate short-term clinical outcomes. Included cases are the first experience with this device and new implantation technique in Europe. Clinical, echocardiographic, and computed tomographic data were analyzed. Endpoints were defined according to Valve Academic Research Consortium-2 and were site reported. RESULTS: Between April and November 2019, 286 consecutive patients undergoing TAVR with the LOTUS Edge system at 18 European centers were included. The mean age and Society of Thoracic Surgeons score were 81.2 ± 6.9 years and 5.2 ± 5.4%, respectively. Nearly one-half of all patients (47.9%) were considered to have complex anatomy. Thirty-day major adverse events included death (2.4% [n = 7]) and stroke (3.5% [n = 10]). After TAVR, the mean aortic valve area was 1.9 ± 0.9 cm2, and the mean transvalvular gradient was 11.9 ± 5.7 mm Hg. None or trace paravalvular leak (PVL) occurred in 84.4% and moderate PVL in 2.0%. There were no cases of severe PVL. New permanent pacemaker (PPM) implantation was required in 25.9% among all patients and 30.8% among PPM-naive patients. CONCLUSIONS: Early experience with the LOTUS Edge system demonstrated satisfactory short-term safety and efficacy, favorable hemodynamic data, and very low rates of PVL in an anatomically complex cohort. New PPM implantation remained high. Further study will evaluate if increasing operator experience with the device and new implantation technique can reduce the incidence of PPM implantation.

Safety and Operational Efficiency of Restructuring and Redeploying a Transcatheter Aortic Valve Replacement Service During the COVID-19 Pandemic: The Oxford Experience.

BACKGROUND: The risk of nosocomial COVID-19 infection for vulnerable aortic stenosis patients and intensive care resource utilization has led to cardiac surgery deferral. Untreated severe symptomatic aortic stenosis has a dismal prognosis. TAVR offers an attractive alternative to surgery as it is not reliant on intensive care resources. We set out to explore the safety and operational efficiency of restructuring a TAVR service and redeploying it to a new non-surgical site during the COVID-19 pandemic. METHODS: The institutional prospective service database was retrospectively interrogated for the first 50 consecutive elective TAVR cases prior to and after our institution's operational adaptations for the COVID-19 pandemic. Our endpoints were VARC-2 defined procedural complications, 30-day mortality or re-admission and service efficiency metrics. RESULTS: The profile of patients undergoing TAVR during the pandemic was similar to patients undergoing TAVR prior to the pandemic with the exception of a lower mean age (79 vs 82 years, p < 0.01) and median EuroScore II (3.1% vs 4.6%, p = 0.01). The service restructuring and redeployment contributed to the pandemic-mandated operational efficiency with a reduction in the distribution of pre-admission hospital visits (3 vs 3 visits, p < 0.001) and the time taken from TAVR clinic to procedure (26 vs 77 days, p < 0.0001) when compared to the pre-COVID-19 service. No statistically significant difference was noted in peri-procedural complications and 30-day outcomes, while post-operative length of stay was significantly reduced (2 vs 3 days, p < 0.0001) when compared to pre-COVID-19 practice. CONCLUSIONS: TAVR service restructuring and redeployment to align with pandemic-mandated healthcare resource rationalization is safe and feasible.

Transcatheter Aortic Valve Implantation in Patients With Severe Aortic Stenosis Hospitalized With Acute Heart Failure.

Optimal timing and outcomes of transcatheter aortic valve implantation (TAVI) in patients presenting with acute heart failure (AHF) remain unclear. In this consecutive cohort of 1,547 patients with severe aortic stenosis undergoing TAVI, the AHF status at admission was collected, and patients were classified into AHF and elective TAVI groups. In the AHF group, early TAVI was defined as TAVI performed ≤60 hours after emergency room arrival. The primary outcome was all-cause mortality at 30-day and 2-year after TAVI. There were 139 (9%) patients who underwent TAVI while hospitalized with AHF. At baseline, this group had higher rates of chronic kidney disease, higher Society of Thoracic Surgeons score, and lower left ventricular ejection fraction. After adjusting for baseline differences, the AHF group had significantly higher all-cause mortality at 30-day and 2-year than the elective TAVI group (8% vs 2%; p = 0.002, and 33% vs 18%; p = 0.002, respectively). In the AHF group, 43 (31%) patients underwent early treatment with TAVI. No significant difference in all-cause mortality at 30-day was observed between early and non-early TAVI groups (5% vs 10%; p = 0.617). All-cause mortality at 2-year was lower in the early TAVI groups (16% vs 40%, log-rank p = 0.022); however, after multivariable adjustment, the difference was barely statistically significant (p = 0.053). In conclusion, TAVI in patients with AHF was associated with worse short and long-term outcomes. In AHF setting, early TAVI did not significantly reduce all-cause mortality at 30-day; however, it showed a strong trend for lower all-cause mortality at 2-year.

Baseline NT-proBNP Accurately Predicts Symptom Response to Transcatheter Aortic Valve Implantation.

Background Up to 30% of patients undergoing transcatheter aortic valve implantation (TAVI) experience minimal symptomatic benefit or die within 1 year, indicating an urgent need for enhanced patient selection. Previous analyses of baseline NT-proBNP (N-terminal pro-brain natriuretic peptide) and TAVI outcomes have assumed a linear relationship, yielding conflicting results. We reexamined the relationship between baseline NT-proBNP and symptomatic improvement after TAVI. Methods and Results Symptom status, clinical and echocardiographic data, and baseline NT-proBNP were reviewed from 144 consecutive patients undergoing TAVI for severe symptomatic aortic stenosis. The primary end point was change in New York Heart Association functional class at 1 year. There was a nonlinear, inverted-U relationship between log-baseline NT-proBNP and post-TAVI change in NYHA class (R2=0.4559). NT-proBNP thresholds of <800 and >10 000 ng/L accurately predicted no symptomatic improvement at 1 year (sensitivity 88%, specificity 83%, positive predictive value 72%, negative predictive value 93%). In adjusted analyses, baseline NT-proBNP outside this "sweet-spot" range was the only factor independently associated with poor functional outcome (high: NT-proBNP >10 000 ng/L, odds ratio [OR], 65; 95% CI, 6-664; low: NT-proBNP <800 ng/L, OR, 73; 95% CI, 7-738). Conclusions Baseline NT-proBNP is a useful prognostic marker to predict poor symptom relief after TAVI and may indicate when intervention is likely to be futile. Both low (<800 ng/L) and very high (>10 000 ng/L) levels are strongly associated with poor functional outcome, suggesting an alternative cause for symptoms in the former scenario and an irrevocably diseased left ventricle in the latter. Further evaluation of this relationship is warranted.

Guidelines in review: Comparison of ESC and ACC/AHA guidelines for the diagnosis and management of patients with stable coronary artery disease.

In 2012, the American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) Task Force on Practice Guidelines jointly with the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons produced a set of recommendations intended to assist physicians in the diagnosis and management of patients with stable ischemic heart disease. Two years later, a focused update on the 2012 guidelines was published. A year before this update, The Task Force on the management of stable coronary artery disease (CAD) of the European Society of Cardiology (ESC) issued a guideline on the management of stable CAD. This document brings together European and American recommendations that include the use of stress testing and non-invasive imaging for the diagnosis and management of patients with known or suspected stable CAD.

CXCR2 Inhibition - a novel approach to treating CoronAry heart DiseAse (CICADA): study protocol for a randomised controlled trial.

BACKGROUND: There is emerging evidence of the central role of neutrophils in both atherosclerotic plaque formation and rupture. Patients with lower neutrophil counts following acute coronary syndromes tend to have a greater coronary flow reserve, which is a strong predictor of long-term cardiovascular health. But so far, no data are available regarding the impact of neutrophil inhibition on cardiovascular clinical or surrogate endpoints. Therefore, the aim of this study is to investigate the effects of AZD5069, a cysteine-X-cysteine chemokine receptor 2 (CXCR2) inhibitor, on coronary flow reserve and coronary structure and function in patients with coronary artery disease. METHODS/DESIGN: Ninety subjects with coronary artery disease undergoing percutaneous coronary intervention will be included in this investigator-driven, randomised, placebo-controlled, double-blind, phase IIa, single-centre study. Participants will be randomised to receive either AZD5069 (40 mg) administered orally twice daily or placebo for 24 weeks. Change in coronary flow reserve as determined by 13N-ammonia positron emission tomography-computed tomography will be the primary outcome. Change in the inflammatory component of coronary plaque structure and the backward expansion wave, an invasive coronary physiological measure of diastolic function, will be assessed as secondary outcomes. DISCUSSION: Cardiovascular surrogate parameters, such as coronary flow reserve, may provide insights into the potential mechanisms of the cardiovascular effects of CXCR2 inhibitors. Currently, ongoing trials do not specifically focus on neutrophil function as a target of intervention, and we therefore believe that our study will contribute to a better understanding of the role of neutrophil-mediated inflammation in coronary artery disease. TRIAL REGISTRATION: EudraCT, 2016-000775-24 . Registered on 22 July 2016. International Standard Randomised Controlled Trial Number, ISRCTN48328178 . Registered on 25 February 2016.

The big parade: emerging percutaneous mitral and tricuspid valve devices.

Over the last decade, percutaneous intervention for the treatment of aortic stenosis has become commonplace with >300,000 implantations performed worldwide. With this now being an established therapy, focus has shifted to the more intricate challenge of mitral and tricuspid valve disease, where there remains a large population of patients with unmet clinical needs. These complex anatomical structures demand unique approaches to treat a wide range of pathologies involving the valve leaflets, annulus and chordae. A large armamentarium of devices is under evaluation in preclinical animal studies or preliminary clinical trials. Herein, we review the technical characteristics of mitral and tricuspid devices in current clinical application and summarise the available data concerning their use in humans.

A Randomised tRial of Expedited transfer to a cardiac arrest centre for non-ST elevation ventricular fibrillation out-of-hospital cardiac arrest: The ARREST pilot randomised trial.

BACKGROUND: Wide variation exists in inter-hospital survival from out-of-hospital cardiac arrest (OHCA). Regionalisation of care into cardiac arrest centres (CAC) may improve this. We report a pilot randomised trial of expedited transfer to a CAC following OHCA without ST-elevation. The objective was to assess the feasibility of performing a large-scale randomised controlled trial. METHODS: Adult witnessed ventricular fibrillation OHCA of presumed cardiac cause were randomised 1:1 to either: (1) treatment: comprising expedited transfer to a CAC for goal-directed therapy including access to immediate reperfusion, or (2) control: comprising current standard of care involving delivery to the geographically closest hospital. The feasibility of randomisation, protocol adherence and data collection of the primary (30-day all-cause mortality) and secondary (cerebral performance category (CPC)) and in-hospital major cardiovascular and cerebrovascular events (MACCE) clinical outcome measures were assessed. RESULTS: Between November 2014 and April 2016, 118 cases were screened, of which 63 patients (53%) met eligibility criteria and 40 of the 63 patients (63%) were randomised. There were no protocol deviations in the treatment arm. Data collection of primary and secondary outcomes was achieved in 83%. There was no difference in baseline characteristics between the groups: 30-day mortality (Intervention 9/18, 50% vs. Control 6/15, 40%; P=0.73), CPC 1/2 (Intervention: 9/18, 50% vs. Control 7/14, 50%; P>0.99) or MACCE (Intervention: 9/18, 50% vs. Control 6/15, 40%; P=0.73). CONCLUSIONS: These findings support the feasibility and acceptability of conducting a large-scale randomised controlled trial of expedited transfer to CAC following OHCA to address a remaining uncertainty in post-arrest care.

Primary Angioplasty For Patients in Cardiogenic Shock: Optimal Management.

Cardiogenic shock complicates approximately 5-10 % of all MI events and remains the most common cause of death among MI cases. Over the past few decades, the mortality rate associated with cardiogenic shock has decreased with the introduction of early revascularisation, although there are limited data for patients with triple-vessel disease and left main stem disease. In more recent years, there have been a number of advances in the mechanical circulatory support devices that can help improve the haemodynamics of patients in cardiogenic shock. Despite these advances, together with progress in the use of inotropes and vasopressors, cardiogenic shock remains associated with high morbidity and mortality rates. This review will outline the management of cardiogenic shock complicating acute MI with a smajor focus on revascularisation techniques and the use of mechanical circulatory support devices.

A prospective, double-blind, randomized controlled trial of the angiotensin-converting enzyme inhibitor Ramipril In Aortic Stenosis (RIAS trial).

AIMS: Angiotensin-converting enzyme (ACE) inhibitors improve left ventricular (LV) remodelling and outcome in heart failure and hypertensive heart disease. They may be similarly beneficial in patients with aortic stenosis (AS), but historical safety concerns have limited their use, and no prospective clinical trials exist. METHODS AND RESULTS: We conducted a prospective, randomized, double-blind, placebo-controlled trial in 100 patients with moderate or severe asymptomatic AS to examine the physiological effects of ramipril, particularly LV mass (LVM) regression. Subjects were randomized to ramipril 10 mg daily (n = 50) or placebo (n = 50) for 1 year, and underwent cardiac magnetic resonance, echocardiography, and exercise testing at 0, 6, and 12 months, with follow-up data available in 77 patients. There was a modest but progressive reduction in LVM (the primary end point) in the ramipril group vs. the placebo group (mean change -3.9 vs. +4.5 g, respectively, P = 0.0057). There were also trends towards improvements in myocardial physiology: the ramipril group showed preserved tissue Doppler systolic velocity compared with placebo (+0.0 vs. -0.5 cm/s, P = 0.04), and a slower rate of progression of the AS (valve area 0.0 cm(2) in the ramipril group vs. -0.2 cm(2) in the placebo arm, P = 0.067). There were no significant differences in major adverse cardiac events. CONCLUSION: ACE inhibition leads to a modest, but progressive reduction in LVM in asymptomatic patients with moderate-severe AS compared with placebo, with trends towards improvements in myocardial physiology and slower progression of valvular stenosis. A larger clinical outcome trial to confirm these findings and explore their clinical relevance is required.