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1.
Lancet ; 402(10410): 1329-1337, 2023 Oct 14.
Article in English | MEDLINE | ID: mdl-37647928

ABSTRACT

BACKGROUND: The International Liaison Committee on Resuscitation has called for a randomised trial of delivery to a cardiac arrest centre. We aimed to assess whether expedited delivery to a cardiac arrest centre compared with current standard of care following resuscitated cardiac arrest reduces deaths. METHODS: ARREST is a prospective, parallel, multicentre, open-label, randomised superiority trial. Patients (aged ≥18 years) with return of spontaneous circulation following out-of-hospital cardiac arrest without ST elevation were randomly assigned (1:1) at the scene of their cardiac arrest by London Ambulance Service staff using a secure online randomisation system to expedited delivery to the cardiac catheter laboratory at one of seven cardiac arrest centres or standard of care with delivery to the geographically closest emergency department at one of 32 hospitals in London, UK. Masking of the ambulance staff who delivered the interventions and those reporting treatment outcomes in hospital was not possible. The primary outcome was all-cause mortality at 30 days, analysed in the intention-to-treat (ITT) population excluding those with unknown mortality status. Safety outcomes were analysed in the ITT population. The trial was prospectively registered with the International Standard Randomised Controlled Trials Registry, 96585404. FINDINGS: Between Jan 15, 2018, and Dec 1, 2022, 862 patients were enrolled, of whom 431 (50%) were randomly assigned to a cardiac arrest centre and 431 (50%) to standard care. 20 participants withdrew from the cardiac arrest centre group and 19 from the standard care group, due to lack of consent or unknown mortality status, leaving 411 participants in the cardiac arrest centre group and 412 in the standard care group for the primary analysis. Of 822 participants for whom data were available, 560 (68%) were male and 262 (32%) were female. The primary endpoint of 30-day mortality occurred in 258 (63%) of 411 participants in the cardiac arrest centre group and in 258 (63%) of 412 in the standard care group (unadjusted risk ratio for survival 1·00, 95% CI 0·90-1·11; p=0·96). Eight (2%) of 414 patients in the cardiac arrest centre group and three (1%) of 413 in the standard care group had serious adverse events, none of which were deemed related to the trial intervention. INTERPRETATION: In adult patients without ST elevation, transfer to a cardiac arrest centre following resuscitated cardiac arrest in the community did not reduce deaths. FUNDING: British Heart Foundation.


Subject(s)
Out-of-Hospital Cardiac Arrest , ST Elevation Myocardial Infarction , Adult , Humans , Male , Female , Adolescent , Out-of-Hospital Cardiac Arrest/therapy , Prospective Studies , Treatment Outcome , London/epidemiology , Randomized Controlled Trials as Topic
2.
Eur Heart J ; 40(5): 422-440, 2019 02 01.
Article in English | MEDLINE | ID: mdl-30608523

ABSTRACT

Transcatheter heart valve interventions have transformed the outcomes of patients with valvular heart disease (VHD) who are unfavourable candidates for surgery. Technological advances have allowed extension of these interventions to younger or lower risk patients and those with other forms of VHD and may in the future permit earlier treatment of VHD in less symptomatic patients or those with moderate disease. The balance of risks and benefits is likely to differ between lower and higher risk patients, and more evidence is needed to evaluate the net benefit of transcatheter technology in these groups. As academic researchers, clinicians, industry, and patient stakeholders collaborate to research these broader indications for transcatheter valve interventions, it is essential to address (i) device durability and deliverability, (ii) specific anatomical needs (e.g. bicuspid aortic valves, aortic regurgitation, mitral and tricuspid valve disease), (iii) operator training, and (iv) the reinforced importance of the multidisciplinary Heart Team.


Subject(s)
Heart Valve Diseases/surgery , Heart Valve Prosthesis Implantation/methods , Heart Valve Prosthesis , Heart Valves/surgery , Heart Valve Prosthesis Implantation/instrumentation , Heart Valve Prosthesis Implantation/trends , Humans , Progression-Free Survival , Prosthesis Design , Transcatheter Aortic Valve Replacement/trends
3.
Circulation ; 136(1): 24-34, 2017 Jul 04.
Article in English | MEDLINE | ID: mdl-28468975

ABSTRACT

BACKGROUND: The mechanisms governing exercise-induced angina and its alleviation by the most commonly used antianginal drug, nitroglycerin, are incompletely understood. The purpose of this study was to develop a method by which the effects of antianginal drugs could be evaluated invasively during physiological exercise to gain further understanding of the clinical impact of angina and nitroglycerin. METHODS: Forty patients (mean age, 65.2±7.6 years) with exertional angina and coronary artery disease underwent cardiac catheterization via radial access and performed incremental exercise using a supine cycle ergometer. As they developed limiting angina, sublingual nitroglycerin was administered to half the patients, and all patients continued to exercise for 2 minutes at the same workload. Throughout exercise, distal coronary pressure and flow velocity and central aortic pressure were recorded with sensor wires. RESULTS: Patients continued to exercise after nitroglycerin administration with less ST-segment depression (P=0.003) and therefore myocardial ischemia. Significant reductions in afterload (aortic pressure, P=0.030) and myocardial oxygen demand were seen (tension-time index, P=0.024; rate-pressure product, P=0.046), as well as an increase in myocardial oxygen supply (Buckberg index, P=0.017). Exercise reduced peripheral arterial wave reflection (P<0.05), which was not further augmented by the administration of nitroglycerin (P=0.648). The observed increases in coronary pressure gradient, stenosis resistance, and flow velocity did not reach statistical significance; however, the diastolic velocity-pressure gradient relation was consistent with a significant increase in relative stenosis severity (k coefficient, P<0.0001), in keeping with exercise-induced vasoconstriction of stenosed epicardial segments and dilatation of normal segments, with trends toward reversal with nitroglycerin. CONCLUSIONS: The catheterization laboratory protocol provides a model to study myocardial ischemia and the actions of novel and established antianginal drugs. Administration of nitroglycerin causes changes in the systemic and coronary circulation that combine to reduce myocardial oxygen demand and to increase supply, thereby attenuating exercise-induced ischemia. Designing antianginal therapies that exploit these mechanisms may provide new therapeutic strategies.


Subject(s)
Angina Pectoris/diagnostic imaging , Angina Pectoris/drug therapy , Cardiac Catheterization/methods , Exercise Test/methods , Nitroglycerin/therapeutic use , Vasodilator Agents/therapeutic use , Aged , Angina Pectoris/physiopathology , Echocardiography, Doppler/methods , Exercise Test/drug effects , Female , Humans , Male , Middle Aged , Nitroglycerin/pharmacology , Pulse Wave Analysis/methods , Single-Blind Method , Vasodilator Agents/pharmacology
4.
Am Heart J ; 204: 92-101, 2018 10.
Article in English | MEDLINE | ID: mdl-30092413

ABSTRACT

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is a global public health issue. There is wide variation in both regional and inter-hospital survival rates from OHCA and overall survival remains poor at 7%. Regionalization of care into cardiac arrest centers (CAC) improves outcomes following cardiac arrest from ST elevation myocardial infarction (STEMI) through concentration of services and greater provider experience. The International Liaison Committee on Resuscitation (ILCOR) recommends delivery of all post-arrest patients to a CAC, but that randomized controlled trials are necessary in patients without ST elevation (STE). METHODS/DESIGN: Following completion of a pilot randomized trial to assess safety and feasibility of conducting a large-scale randomized controlled trial in patients following OHCA of presumed cardiac cause without STE, we present the rationale and design of A Randomized tRial of Expedited transfer to a cardiac arrest center for non-ST elevation OHCA (ARREST). In total 860 patients will be enrolled and randomized (1:1) to expedited transfer to CAC (24/7 access to interventional cardiology facilities, cooling and goal-directed therapies) or to the current standard of care, which comprises delivery to the nearest emergency department. Primary outcome is 30-day all-cause mortality and secondary outcomes are 30-day and 3-month neurological status and 3, 6 and 12-month mortality. Patients will be followed up for one year after enrolment. CONCLUSION: Post-arrest care is time-critical, requires a multi-disciplinary approach and may be more optimally delivered in centers with greater provider experience. This trial would help to demonstrate if regionalization of post-arrest care to CACs reduces mortality in patients without STE, which could dramatically reshape emergency care provision.


Subject(s)
Cardiac Care Facilities , Myocardial Infarction/mortality , Myocardial Infarction/therapy , Out-of-Hospital Cardiac Arrest/mortality , Out-of-Hospital Cardiac Arrest/therapy , Patient Transfer , Cardiac Care Facilities/economics , Cardiopulmonary Resuscitation , Cost-Benefit Analysis , Emergency Service, Hospital/economics , Humans , London , Survival Rate , Time-to-Treatment , Triage
5.
Am J Physiol Heart Circ Physiol ; 310(9): H1242-58, 2016 05 01.
Article in English | MEDLINE | ID: mdl-26945076

ABSTRACT

This work presents a mathematical model of the metabolic feedback and adrenergic feedforward control of coronary blood flow that occur during variations in the cardiac workload. It is based on the physiological observations that coronary blood flow closely follows myocardial oxygen demand, that myocardial oxygen debts are repaid, and that control oscillations occur when the system is perturbed and so are phenomenological in nature. Using clinical data, we demonstrate that the model can provide patient-specific estimates of coronary blood flow changes between rest and exercise, requiring only the patient's heart rate and peak aortic pressure as input. The model can be used in zero-dimensional lumped parameter network studies or as a boundary condition for three-dimensional multidomain Navier-Stokes blood flow simulations. For the first time, this model provides feedback control of the coronary vascular resistance, which can be used to enhance the physiological accuracy of any hemodynamic simulation, which includes both a heart model and coronary arteries. This has particular relevance to patient-specific simulation for which heart rate and aortic pressure recordings are available. In addition to providing a simulation tool, under our assumptions, the derivation of our model shows that ß-feedforward control of the coronary microvascular resistance is a mathematical necessity and that the metabolic feedback control must be dependent on two error signals: the historical myocardial oxygen debt, and the instantaneous myocardial oxygen deficit.


Subject(s)
Computer Simulation , Coronary Circulation , Coronary Vessels/physiology , Exercise , Hemodynamics , Models, Cardiovascular , Muscle Contraction , Muscle, Skeletal/physiology , Adaptation, Physiological , Arterial Pressure , Autonomic Nervous System/physiology , Coronary Vessels/innervation , Heart Rate , Humans , Muscle, Skeletal/metabolism , Myocardium/metabolism , Oxygen/blood , Oxygen Consumption , Time Factors , Vascular Resistance
7.
Basic Res Cardiol ; 110(3): 23, 2015 May.
Article in English | MEDLINE | ID: mdl-25837837

ABSTRACT

Cardiac troponins are released and cleared slowly after myocardial injury, complicating the diagnosis of early, and recurrent, acute myocardial infarction. Cardiac myosin-binding protein C (cMyC) is a similarly cardiac-restricted protein that may have different release/clearance kinetics. Using novel antibodies raised against the cardiac-specific N-terminus of cMyC, we used confocal microscopy, immunoblotting and immunoassay to document its location and release. In rodents, we demonstrate rapid release of cMyC using in vitro and in vivo models of acute myocardial infarction. In patients, with ST elevation myocardial infarction (STEMI, n = 20), undergoing therapeutic ablation of septal hypertrophy (TASH, n = 20) or having coronary artery bypass surgery (CABG, n = 20), serum was collected prospectively and frequently. cMyC appears in the serum as full-length and fragmented protein. Compared to cTnT measured using a contemporary high-sensitivity commercial assay, cMyC peaks earlier (STEMI, 9.3 ± 3.1 vs 11.8 ± 3.4 h, P < 0.007; TASH, 9.7 ± 1.4 vs 21.6 ± 1.4 h, P < 0.0001), accumulates more rapidly (during first 4 h after TASH, 25.8 ± 1.9 vs 4.0 ± 0.4 ng/L/min, P < 0.0001) and disappears more rapidly (post-CABG, decay half-time 5.5 ± 0.8 vs 22 ± 5 h, P < 0.0001). Our results demonstrate that following defined myocardial injury, the rise and fall in the serum of cMyC is more rapid than that of cTnT. We speculate that these characteristics could enable earlier diagnosis of myocardial infarction and reinfarction in suspected non-STEMI, a population not included in this early translational study.


Subject(s)
Biomarkers/blood , Carrier Proteins/blood , Myocardial Infarction/blood , Aged , Animals , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunoblotting , Male , Middle Aged , Rats , Rats, Wistar , Surface Plasmon Resonance
8.
Cardiovasc Diabetol ; 14: 27, 2015 Feb 19.
Article in English | MEDLINE | ID: mdl-25848859

ABSTRACT

BACKGROUND: Glucagon-like peptide-1 is an incretin hormone essential for normal human glucose homeostasis. Expression of the glucagon-like peptide-1 receptor in the myocardium has fuelled growing interest in the direct and indirect cardiovascular effects of native glucagon-like peptide-1, its degradation product glucagon-like peptide-1(9-36), and the synthetic glucagon-like peptide-1 receptor agonists. Preclinical studies have demonstrated cardioprotective actions of all three compounds in the setting of experimental myocardial infarction and left ventricular systolic dysfunction. This has led to Phase 2 trials of native glucagon-like peptide-1 and incretin-based therapies in humans with and without Type 2 diabetes mellitus. These studies have demonstrated the ability of glucagon-like peptide-1, independent of glycaemic control, to positively modulate the metabolic and haemodynamic parameters of individuals with coronary artery disease and left ventricular systolic dysfunction. We aim to add to this growing body of evidence by studying the effect of chronic glucagon-like peptide-1 receptor activation on exercise-induced ischaemia in patients with chronic stable angina managed conservatively or awaiting revascularisation. The hypothesis being liraglutide, a subcutaneously injectable glucagon-like peptide-1 receptor agonist, is able to improve exercise haemodynamics in patients with obstructive coronary artery disease when compared with saline placebo. METHODS AND DESIGN: The Liraglutide to Improve corONary haemodynamics during Exercise streSS (LIONESS) trial is an investigator-initiated single-centre randomised double-blinded placebo-controlled crossover proof-of-principle physiological study. Primary endpoints are change in rate pressure product at 0.1 mV ST-segment depression and change in degree of ST-segment depression at peak exercise during sequential exercise tolerance testing performed over a 6-week study period in which 26 patients will be randomised to either liraglutide or saline with crossover to the opposing regimen at week 3. DISCUSSION: The study will be conducted in accordance with the principles of Good Clinical Practice and the Declaration of Helsinki. The local Research Ethics Committee and Medicines and Healthcare Products Regulatory Agency have approved the study. TRIAL REGISTRATION: National Institute of Health Research Clinical Research Network (NIHR CRN) Portfolio ID 11112 and ClinicalTrials.gov Identifier NCT02315001.


Subject(s)
Exercise Test/drug effects , Glucagon-Like Peptide-1 Receptor/agonists , Hemodynamics/drug effects , Hypoglycemic Agents/therapeutic use , Liraglutide/therapeutic use , Angina, Stable/diagnosis , Angina, Stable/drug therapy , Cross-Over Studies , Double-Blind Method , Exercise Test/methods , Glucagon-Like Peptide-1 Receptor/metabolism , Hemodynamics/physiology , Humans , Hypoglycemic Agents/pharmacology , Liraglutide/pharmacology
9.
Eur Heart J ; 35(40): 2821-30, 2014 Oct 21.
Article in English | MEDLINE | ID: mdl-24849105

ABSTRACT

AIMS: Coronary artery bypass grafting (CABG) has been considered the standard of care for patients with three-vessel disease (3VD), but long-term comparative results from randomized trials of CABG vs. percutaneous coronary intervention (PCI) using drug-eluting stents (DES) remain limited. METHODS AND RESULTS: Patients with de novo 3VD or left main disease were randomly assigned to PCI with the paclitaxel-eluting first-generation stent or CABG in the SYNTAX trial. This pre-specified analysis presents the 5-year outcomes of patients with 3VD (n = 1095). The rate of major adverse cardiac and cerebrovascular events (MACCE) was significantly higher in patients with PCI compared with CABG (37.5 vs. 24.2%, respectively; P < 0.001). Percutaneous coronary intervention as opposed to CABG resulted in significantly higher rates of the composite of death/stroke/myocardial infarction (MI) (22.0 vs. 14.0%, respectively; P < 0.001), all-cause death (14.6 vs. 9.2%, respectively; P = 0.006), MI (9.2 vs. 4.0%, respectively; P = 0.001), and repeat revascularization (25.4 vs. 12.6%, respectively; P < 0.001); however, stroke was similar between groups at 5 years (3.0 vs. 3.5%, respectively; P = 0.66). Results were dependent on lesion complexity (P for interaction = 0.12); in patients with a low (0-22) SYNTAX score, PCI vs. CABG resulted in similar rates of MACCE (33.3% vs. 26.8%, respectively; P = 0.21) but significantly more repeat revascularization (25.4% vs. 12.6%, respectively; P = 0.038), while in intermediate (23-32) or high (≥ 33) SYNTAX score terciles, CABG demonstrated clear superiority in terms of MACCE, death, MI, and repeat revascularization. Differences in MACCE between PCI and CABG were larger in diabetics [hazard ratio (HR) = 2.30] than non-diabetics (HR = 1.51), although the P for interaction failed to reach significance for MACCE (P for interaction = 0.095) or any of the other endpoints. CONCLUSION: Five-year results of patients with 3VD treated with CABG or PCI using the first-generation paclitaxel-eluting DES suggest that CABG should remain the standard of care as it resulted in significantly lower rates of death, MI, and repeat revascularization, while stroke rates were similar. For patients with low SYNTAX scores, PCI is an acceptable revascularization strategy, although at a price of significantly higher rates of repeat revascularization. CLINICAL TRIAL REGISTRATION: NCT00114972.


Subject(s)
Coronary Artery Bypass/methods , Coronary Artery Disease/surgery , Percutaneous Coronary Intervention/methods , Coronary Artery Disease/mortality , Diabetic Angiopathies/drug therapy , Diabetic Angiopathies/mortality , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Myocardial Revascularization/methods , Myocardial Revascularization/mortality , Prospective Studies , Stroke/etiology , Stroke/mortality , Treatment Outcome
11.
Lancet ; 382(9892): 633-43, 2013 Aug 17.
Article in English | MEDLINE | ID: mdl-23953387

ABSTRACT

Acute ST-segment elevation myocardial infarction (STEMI) is a dynamic, thrombus-driven event. As understanding of its pathophysiology has improved, the central role of platelets in initiation and orchestration of this process has become clear. Key components of STEMI include formation of occlusive thrombus, mediation and ultimately amplification of the local vascular inflammatory response resulting in increased vasoreactivity, oedema formation, and microvascular obstruction. Activation, degranulation, and aggregation of platelets are the platforms from which these components develop. Therefore, prompt, potent, and predictable antithrombotic therapy is needed to optimise clinical outcomes after primary percutaneous coronary intervention. We review present pharmacological and mechanical adjunctive therapies for reperfusion and ask what is the optimum combination when primary percutaneous coronary intervention is used as the mode of revascularisation in patients with STEMI.


Subject(s)
Myocardial Infarction/surgery , Myocardial Reperfusion , Percutaneous Coronary Intervention , Adenosine Monophosphate/administration & dosage , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Administration, Oral , Anticoagulants/therapeutic use , Combined Modality Therapy , Humans , Infusions, Parenteral , Integrin beta3/drug effects , Myocardial Infarction/drug therapy , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/therapeutic use , Platelet Membrane Glycoprotein IIb/drug effects , Thrombolytic Therapy
12.
Postgrad Med J ; 90(1069): 648-56, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25335796

ABSTRACT

The phenomenon of warm-up angina was first noted over 200 years ago. It describes the curious observation whereby exercise-induced ischaemia on second effort is significantly reduced or even abolished if separated from first effort by a brief rest period. However, the precise mechanism via which this cardio-protection occurs remains uncertain. Three possible explanations for reduced myocardial ischaemia on second effort include: first, an improvement in myocardial perfusion; second, increased myocardial resistance to ischaemia similar to ischaemic preconditioning; and third, reduced cardiac work through better ventricular-vascular coupling. Obtaining accurate coronary physiological measurements in the catheter laboratory throughout exercise demands a complex research protocol. In the 1980s, studies into warm-up angina relied on great cardiac vein thermo-dilution to estimate coronary blood flow. This technique has subsequently been shown to be inaccurate. However exercise physiology in the catheter laboratory has recently been resurrected with the advent of coronary artery wires that allow continuous measurement of distal coronary artery pressure and blood flow velocity. This review summarises the intriguing historical background to warm-up angina, and provides a concise critique of the important studies investigating mechanisms behind this captivating cardio-protective phenomenon.

13.
JACC Cardiovasc Interv ; 17(12): 1440-1451, 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38639690

ABSTRACT

BACKGROUND: Thirty-day outcomes with the investigational Intrepid transapical (TA) transcatheter mitral valve replacement (TMVR) system have previously demonstrated good technical success, but longer-term outcomes in larger cohorts need to be evaluated. OBJECTIVES: The authors sought to evaluate the 2-year safety and performance of the Intrepid TA-TMVR system in patients with symptomatic, ≥moderate-severe mitral regurgitation (MR) and high surgical risk. METHODS: Patient eligibility was determined by local heart teams and approved by a central screening committee. Clinical events were adjudicated by an independent clinical events committee. Echocardiography was evaluated by an independent core laboratory. RESULTS: The cohort included 252 patients that were enrolled at 58 international sites before February 2021 as part of the global Pilot Study (n = 95) or APOLLO trial (primary cohort noneligible + TA roll-ins, n = 157). Mean age was 74.2 years, mean STS-PROM was 6.3%, 60.3% were male, and 80.6% were in NYHA functional class III/IV. Most presented with secondary MR (70.1%), and nearly all had ≥moderate-severe MR (98.4%). All-cause mortality was 13.1% (30-day), 27.3% (1-year), and 36.2% (2-year). The 30-day ≥major bleeding event rate was 22.3%. Heart failure rehospitalization was 9.6% (30-day) and 36.2% (2-year). At 2 years, >50% of patients were alive with improvement in NYHA functional class (82.1%, class I/II), and all patients with available echocardiograms had ≤mild MR. CONCLUSIONS: This analysis represents the largest reported TA-TMVR experience with the longest follow-up in high-risk ≥moderate-severe MR patients. Early mortality and heart failure rehospitalizations were significant, exacerbated by early TA-related bleeding events; however, meaningful improvements in clinical outcomes and marked reductions in MR severity were observed through 2 years.


Subject(s)
Cardiac Catheterization , Heart Valve Prosthesis Implantation , Heart Valve Prosthesis , Mitral Valve Insufficiency , Mitral Valve , Recovery of Function , Severity of Illness Index , Humans , Mitral Valve Insufficiency/diagnostic imaging , Mitral Valve Insufficiency/physiopathology , Mitral Valve Insufficiency/surgery , Mitral Valve Insufficiency/mortality , Female , Male , Aged , Mitral Valve/diagnostic imaging , Mitral Valve/physiopathology , Mitral Valve/surgery , Treatment Outcome , Heart Valve Prosthesis Implantation/instrumentation , Heart Valve Prosthesis Implantation/adverse effects , Heart Valve Prosthesis Implantation/mortality , Cardiac Catheterization/adverse effects , Cardiac Catheterization/instrumentation , Cardiac Catheterization/mortality , Time Factors , Aged, 80 and over , Risk Factors , Prosthesis Design , Predictive Value of Tests , Postoperative Complications/etiology , Middle Aged , Hemodynamics , Patient Readmission , Echocardiography
14.
Circulation ; 126(22): 2565-74, 2012 Nov 27.
Article in English | MEDLINE | ID: mdl-23124033

ABSTRACT

BACKGROUND: The mechanisms of reduced angina on second exertion in patients with coronary arterial disease, also known as the warm-up angina phenomenon, are poorly understood. Adaptations within the coronary and systemic circulations have been suggested but never demonstrated in vivo. In this study we measured central and coronary hemodynamics during serial exercise. METHODS AND RESULTS: Sixteen patients (15 male, 61±4.3 years) with a positive exercise ECG and exertional angina completed the protocol. During cardiac catheterization via radial access, they performed 2 consecutive exertions (Ex1, Ex2) using a supine cycle ergometer. Throughout exertions, distal coronary pressure and flow velocity were recorded in the culprit vessel using a dual sensor wire while central aortic pressure was recorded using a second wire. Patients achieved a similar workload in Ex2 but with less ischemia than in Ex1 (P<0.01). A 33% decline in aortic pressure augmentation in Ex2 (P<0.0001) coincided with a reduction in tension time index, a major determinant of left ventricular afterload (P<0.001). Coronary stenosis resistance was unchanged. A sustained reduction in coronary microvascular resistance resulted in augmented coronary flow velocity on second exertion (both P<0.001). These changes were accompanied by a 21% increase in the energy of the early diastolic coronary backward-traveling expansion, or suction, wave on second exercise (P<0.05), indicating improved microvascular conductance and enhanced left ventricular relaxation. CONCLUSIONS: On repeat exercise in patients with effort angina, synergistic changes in the systemic and coronary circulations combine to improve vascular-ventricular coupling and enhance myocardial perfusion, thereby potentially contributing to the warm-up angina phenomenon.


Subject(s)
Adaptation, Physiological/physiology , Angina Pectoris/physiopathology , Coronary Circulation/physiology , Exercise/physiology , Hemodynamics/physiology , Aged , Aorta/physiology , Blood Flow Velocity/physiology , Blood Pressure/physiology , Female , Humans , Male , Middle Aged , Vasodilation/physiology , Ventricular Function, Left/physiology , Ventricular Pressure/physiology
15.
Heart ; 109(4): 322-329, 2023 01 27.
Article in English | MEDLINE | ID: mdl-36526337

ABSTRACT

Aortic stenosis (AS) is the most common valvular heart disorder in the elderly population. As a result of the shared pathophysiological processes, AS frequently coexists with coronary artery disease (CAD). These patients have traditionally been managed through surgical aortic valve replacement (SAVR) and coronary artery bypass grafting. However, increasing body of evidence supports transcatheter aortic valve implantation (TAVI) as an alternative treatment for severe AS across the spectrum of operative risk. This has created the potential for treating AS and concurrent CAD completely percutaneously. In this review we consider the evidence guiding the optimal management of patients with severe AS and CAD. While invasive coronary angiography plays a central role in detecting CAD in patients with AS undergoing surgery or TAVI, the benefits of complementary functional assessment of coronary stenosis in the context of AS have not been fully established. Although the indications for revascularisation of significant proximal CAD in SAVR patients have not recently changed, routine revascularisation of all significant CAD before TAVI in patients with minimal angina is not supported by the latest evidence. Several ongoing trials will provide new insights into physiology-guided revascularisation in TAVI recipients. The role of the heart team remains essential in this complex patient group, and if revascularisation is being considered careful evaluation of clinical, anatomical and procedural factors is essential for individualised decision-making.


Subject(s)
Aortic Valve Stenosis , Coronary Artery Disease , Heart Valve Prosthesis Implantation , Transcatheter Aortic Valve Replacement , Aged , Humans , Coronary Artery Disease/diagnosis , Coronary Artery Disease/diagnostic imaging , Aortic Valve Stenosis/complications , Aortic Valve Stenosis/diagnosis , Aortic Valve Stenosis/surgery , Transcatheter Aortic Valve Replacement/adverse effects , Aortic Valve/surgery , Coronary Angiography , Heart Valve Prosthesis Implantation/adverse effects , Treatment Outcome , Risk Factors
16.
J Invasive Cardiol ; 34(11): E820-E821, 2022 11.
Article in English | MEDLINE | ID: mdl-36318462

ABSTRACT

A 76-year-old-male transferred to our center with severe breathlessness (New York Heart Association class III-IV). He was afebrile, hypoxic, and tachycardic with a wide pulse-pressure. Chest auscultation revealed a systolic and early diastolic murmur. Two weeks prior to admission, he reported severe cellulitis treated with intravenous antibiotics. Transthoracic echocardiogram demonstrated severe aortic valve (AoV) stenosis and evidence of AoV disruption with mobile vegetations and severe aortic regurgitation (AR) in keeping with plausible infectious endocarditis (IE). Following 3 sets of blood cultures, we treated the patient with intravenous antibiotics and diuretics. Blood cultures were negative, likely due to previous antibiotics treatment. Due to the acute decompensation, he underwent early heart team discussion with a view to urgent surgical AoV replacement. This case example suggests that TAVR with cerebral protection might be a safe treatment option in inoperable patients with AoV IE.


Subject(s)
Aortic Valve Stenosis , Endocarditis , Transcatheter Aortic Valve Replacement , Humans , Male , Aged , Aortic Valve/surgery , Off-Label Use , Aortic Valve Stenosis/surgery , Anti-Bacterial Agents/therapeutic use
17.
Front Cardiovasc Med ; 9: 971762, 2022.
Article in English | MEDLINE | ID: mdl-36479570

ABSTRACT

Since the first groundbreaking procedure in 2002, transcatheter aortic valve implantation (TAVI) has revolutionized the management of aortic stenosis (AS). Through striking developments in pertinent equipment and techniques, TAVI has now become the leading therapeutic strategy for aortic valve replacement in patients with severe symptomatic AS. The procedure streamlining from routine use of conscious sedation to a single arterial access approach, the newly adapted implantation techniques, and the introduction of novel technologies such as intravascular lithotripsy and the refinement of valve-bioprosthesis devices along with the accumulating experience have resulted in a dramatic reduction of complications and have improved associated outcomes that are now considered comparable or even superior to surgical aortic valve replacement (SAVR). These advances have opened the road to the use of TAVI in younger and lower-risk patients and up-to-date data from landmark studies have now established the outstanding efficacy and safety of TAVI in patients with low-surgical risk impelling the most recent ESC guidelines to propose TAVI, as the main therapeutic strategy for patients with AS aged 75 years or older. In this article, we aim to summarize the most recent advances and the current clinical aspects involving the use of TAVI, and we also attempt to highlight impending concerns that need to be further addressed.

18.
J Invasive Cardiol ; 34(9): E660-E664, 2022 09.
Article in English | MEDLINE | ID: mdl-35916923

ABSTRACT

BACKGROUND: Guidelines endorse a heart team (HT) approach to standardize the decision-making process for patients with complex coronary artery disease (CAD). With percutaneous treatment options for complex CAD increasing, we hypothesized that practice had changed over the past decade-and that more individuals, previously deemed too high risk for intervention, would now be referred for either surgical or percutaneous revascularization. METHODS: This observational study was conducted at St Thomas' Hospital (London, United Kingdom). All patients discussed at HT meetings were recorded and treatment recommendations audited. A subset of historic cases was selected for blinded, repeat discussion. RESULTS: From April 2018 to 2019, a total of 52 HT meetings discussing 375 cases were held. Patients tended to be male, with a majority demonstrating multivessel CAD in the context of preserved left ventricular function. SYNTAX scores were balanced across the tertiles. Thirty-five percent of patients had at least 1 chronic total occlusion (mean J-CTO, 3 [interquartile range, 2-3]), affecting the right coronary artery in 60%. Fifteen historic patients with isolated CTOs were re-presented an average of 8 years later; only 3 patients received the same outcome, with 80% now receiving a recommendation for revascularization over medical therapy. CONCLUSIONS: A dedicated program supporting complex coronary intervention is associated with a change in treatment recommendations issued by the local HT. In line with international guidelines, this might indicate that any complex or multivessel CAD should be discussed at HT meetings with, ideally, the presence of CTO operators.


Subject(s)
Coronary Artery Disease , Coronary Occlusion , Percutaneous Coronary Intervention , Chronic Disease , Coronary Artery Bypass , Coronary Artery Disease/diagnosis , Coronary Artery Disease/surgery , Coronary Occlusion/diagnosis , Coronary Occlusion/surgery , Decision Making , Humans , Male , Percutaneous Coronary Intervention/adverse effects , Risk Factors , Treatment Outcome , United Kingdom
19.
Heart ; 108(8): 639-647, 2022 04.
Article in English | MEDLINE | ID: mdl-35058295

ABSTRACT

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.


Subject(s)
Aortic Valve Stenosis , Endocarditis, Bacterial , Endocarditis , Heart Valve Prosthesis Implantation , Heart Valve Prosthesis , Transcatheter Aortic Valve Replacement , Aortic Valve/surgery , Aortic Valve Stenosis/complications , Endocarditis/epidemiology , Endocarditis/etiology , Endocarditis/surgery , Endocarditis, Bacterial/surgery , Heart Valve Prosthesis/adverse effects , Heart Valve Prosthesis Implantation/adverse effects , Humans , Male , Risk Factors , Transcatheter Aortic Valve Replacement/adverse effects , Treatment Outcome
20.
JACC Cardiovasc Interv ; 15(15): 1543-1554, 2022 08 08.
Article in English | MEDLINE | ID: mdl-35926921

ABSTRACT

BACKGROUND: As transcatheter aortic valve (TAV) replacement is increasingly used in patients with longer life expectancy, a sizable proportion will require redo TAV replacement (TAVR). The unique configuration of balloon-expandable TAV (bTAV) vs a self-expanding TAV (sTAV) potentially affects TAV-in-TAV outcome. OBJECTIVES: The purpose of this study was to better inform prosthesis selection, TAV-in-TAV outcomes were assessed according to the type of initial and subsequent TAV. METHODS: Patients from the Redo-TAVR registry were analyzed using propensity weighting according to their initial valve type (bTAV [n = 115] vs sTAV [n = 106]) and subsequent valve type (bTAV [n = 130] vs sTAV [n = 91]). RESULTS: Patients with failed bTAVs presented later (vs sTAV) (4.9 ± 2.1 years vs 3.7 ± 2.3 years; P < 0.001), with smaller effective orifice area (1.0 ± 0.7 cm2 vs 1.3 ± 0.8 cm2; P = 0.018) and less frequent dominant regurgitation (16.2% vs 47.3%; P < 0.001). Mortality at 30 days was 2.3% (TAV-in-bTAV) vs 0% (TAV-in-sTAV) (P = 0.499) and 1.7% (bTAV-in-TAV) vs 1.0% (sTAV-in-TAV) (P = 0.612); procedural safety was 72.6% (TAV-in-bTAV) vs 71.2% (TAV-in-sTAV) (P = 0.817) and 73.2% (bTAV-in-TAV) vs 76.5% (sTAV-in-TAV) (P = 0.590). Device success was similar according to initial valve type but higher with subsequent sTAV vs bTAV (77.2% vs 64.3%; P = 0.045), primarily because of lower residual gradients (10.3 mm Hg [8.9-11.7 mm Hg] vs 15.2 mm Hg [13.2-17.1 mm Hg]; P < 0.001). Residual regurgitation (moderate or greater) was similar after bTAV-in-TAV and sTAV-in-TAV (5.7%) and nominally higher after TAV-in-bTAV (9.1%) vs TAV-in-sTAV (4.4%) (P = 0.176). CONCLUSIONS: In selected patients, no association was observed between TAV type and redo TAVR safety or mortality, yet subsequent sTAV was associated with higher device success because of lower redo gradients. These findings are preliminary, and more data are needed to guide valve choice for redo TAVR.


Subject(s)
Aortic Valve Stenosis , Heart Valve Prosthesis , Transcatheter Aortic Valve Replacement , Aortic Valve/diagnostic imaging , Aortic Valve/surgery , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/surgery , Humans , Prosthesis Design , Registries , Risk Factors , Treatment Outcome
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