Frailty and transcatheter valve intervention: A narrative review.

Frailty is a common clinical syndrome that portends poor peri-procedural outcomes and increased mortality following transcatheter valve interventions. We reviewed frailty assessment tools in transcatheter intervention cohorts to recommend a pathway for preprocedural frailty assessment in patients referred for transcatheter valve procedures, and evaluated current evidence for frailty interventions and their efficacy in transcatheter intervention. We recommend the use of a frailty screening instrument to identify patients as frail, with subsequent referral for comprehensive geriatric assessment in these patients, to assist in selecting appropriate patients and then optimizing them for transcatheter valve interventions. Interventions to reduce preprocedural frailty are not well defined, however, data from limited cohort studies support exercise-based interventions to increase functional capacity and reduce frailty in parallel with preprocedural medical optimization.

Interpretation of the central aortic pressure waveform in elderly patients with aortic stenosis.

The central aortic pressure waveform, while simple in form, is complex in its physiological interpretation. Although general agreement has been reached on the contour and mechanisms responsible for pressure waveforms in the ascending aorta of healthy humans, in recent years there has been increasing interest in the contour of the pressure wave in elderly patients with aortic valve stenosis (AS). As aortic valve leaflets succumb to fibrosis and calcification, they increase opposition to forward flow. This results in a protracted pressure rise and manifests as the classical finding of pulsus parvus et tardus. Equally, changes to arterial properties (including elasticity and geometry) and pulse wave velocity (PWV) with age, heart failure, or hypertension can cause profound changes to the contour. Increased accessibility of methods to measure the central aortic pressure waveform, as well as the rapid uptake of transcatheter aortic valve implantation technologies, has created a renewed focus on better understanding of characteristic perturbations to the waveform in elderly patients with AS. In this review, we investigate the evolution of our understanding of the central aortic pressure waveform in varying AS disease states to highlight the importance of the physiological and biological basis for alterations in this waveform.

Ageing, Hypertension and Aortic Valve Stenosis: A Conscious Uncoupling.

Aortic valve stenosis (AS) is no longer considered to be a disease of fixed left ventricular (LV) afterload (due to an obstructive valve), but rather, functions as a series circuit with important contributions from both the valve and ageing vasculature. Patients with AS are frequently elderly, with hypertension and a markedly remodelled aorta. The arterial component is sizable, and yet, the contribution of ventricular afterload has been difficult to determine. Arterial stiffening increases the speed of propagation of the blood pressure wave along the central arteries (estimated as the pulse wave velocity), which results in an earlier return of reflected waves. The effect is to augment blood pressure in the proximal aorta during systole, increasing the central pulse pressure and, in turn, placing even greater afterload on the heart. Elevated global LV afterload is known to have adverse consequences on LV remodelling, function and survival in patients with AS. Consequently, there is renewed focus on methods to estimate the relative contributions of local versus global changes in arterial mechanics and valvular haemodynamics in patients with AS. We present a review on existing and upcoming methods to quantify valvulo-arterial impedance and thereby global LV load in patients with AS.

Peri-procedural management of transcatheter mitral valve replacement in patients with heart failure.

Over the past decade, transcatheter mitral valve replacement (TMVR) technologies have evolved with the objective of improving outcomes for patients with severe mitral regurgitation (MR) deemed unsuitable for conventional mitral valve surgery. Although the safety and efficacy of transcatheter edge-to-edge mitral valve repair (TEER) is well-established, there is a sense amongst innovators that a major advantage of TMVR may be to offer a more complete solution for the correction of MR in patients whose complex anatomy means that the likelihood of achieving grade 0 or 1 MR with TEER is low. However, abrupt correction of MR in a poorly prepared left ventricle poses a number of unique haemodynamic challenges, particularly when sudden elimination of regurgitant flow causes a relative increase in left ventricular (LV) afterload. Rapid reduction in LV cavity size following MR elimination may itself result in relative LV outflow tract obstruction (LVOTO), irrespective of the intrinsic risk of LVOTO associated with TMVR. Nevertheless, TMVR on a beating heart affords the opportunity to study real-time invasive cardiac indices in high-risk patients with acute reversal of severe MR.

Key Echocardiographic Considerations for Tricuspid Valve Transcatheter Edge-to-Edge Repair.

Chronic tricuspid regurgitation (TR) results in progressive right ventricular (RV) volume overload, followed by right-sided chamber dilatation, RV systolic dysfunction, and eventual low-output cardiac failure. Severe TR is associated with considerable morbidity and mortality, and yet until recently, patients in the late stage of their disease course had limited treatment options. Cognizant of the high mortality rates associated with surgical intervention, tricuspid valve (TV) transcatheter edge-to-edge repair (TEER) has emerged as a promising solution for patients with severe TR. As has been learned from the transcatheter mitral valve TEER experience, detailed morphological and mechanistic assessment of the TV with transthoracic and transesophageal imaging is essential to optimal patient selection and procedural success. The current review will provide a comprehensive overview of TV anatomy, the updated mechanistic classification of TR, and key echocardiographic considerations in the evaluation, management, and follow-up of patients undergoing TV TEER.

Pulsatile energy consumption as a surrogate marker for vascular afterload improves with time post transcatheter aortic valve replacement in patients with aortic stenosis.

The effect of arterial stiffening on elevated pulsatile left ventricular afterload patients with aortic stenosis (AS) is pronounced beyond systemic hypertension. Circulatory afterload pulsatile efficiency (CAPE) is a marker of vascular function, defined as the ratio of steady state energy consumption (SEC) to maintain systemic circulation and pulsatile energy consumption (PEC). Twenty patients aged 80 ± 7 years were assessed at baseline and a median of 60 days post transcatheter aortic valve replacement (TAVR), with pulsatile vascular load calculated using simultaneous radial applanation tonometry derived aortic pressure and cardiac magnetic resonance phase-contrast imaging derived ascending aortic flow. Eight out of 20 patients had a reduction in PEC post TAVR, and the reduction of PEC correlated strongly with the number of days post TAVR (R = 0.62, P < 0.01). Patients assessed within the 100 days of TAVR had a rise in their PEC when compared to baseline (0.19 ± 0.09 vs 0.14 ± 0.08 W, P = 0.04). Baseline PEC correlated moderately with baseline SEC (R = 0.49, P = 0.03), and a high baseline PEC was predictive of post TAVR PEC reduction (R = 0.54, P =0.01). Overall, no significant differences were found between baseline and post TAVR for systolic aortic pressure (131 ± 20 vs 131 ± 20 mmHg), systemic vascular resistance (1894 ± 493 vs 2015 ± 519 dynes.s/cm5), aortic valve ejection time (337 ± 22 vs 324 ± 34 ms) or aortic characteristic impedance (120 ± 48 vs 107 ± 41 dynes.s/cm5). Improved flow profiles after TAVR likely unmask the true vascular properties by altering ventriculo-valvulo-arterial coupling, leading to downstream vascular remodelling secondary to flow conditioning, and results in eventual improvement of pulsatile afterload as reflected by our proposed index of CAPE.

Tricuspid Regurgitation After Heart Transplantation: The Cause or the Result of Graft Dysfunction?

BACKGROUND: Tricuspid regurgitation (TR) is common following heart transplantation and has been shown to adversely influence patient outcomes. The aim of this study was to identify causes of progression to moderate-severe TR in the first 2 y after transplantation. METHODS: This was a retrospective, single-center study of all patients who underwent heart transplantation over a 6-y period. Transthoracic echocardiogram (TTE) was performed at month 0, between 6 and 12 mo, and 1-2 y postoperatively to determine the presence and severity of TR. RESULTS: A total of 163 patients were included, of whom 142 underwent TTE before first endomyocardial biopsy. At month 0, 127 (78%) patients had nil-mild TR before first biopsy, whereas 36 (22%) had moderate-severe TR. In patients with nil-mild TR, 9 (7%) progressed to moderate-severe TR by 6 mo and 1 underwent tricuspid valve (TV) surgery. Of patients with moderate-severe TR before first biopsy, by 2 y, 3 had undergone TV surgery. The use of postoperative extracorporeal membrane oxygenation (ECMO) in the latter group was significant (78%; P < 0.05) as was rejection profile ( P = 0.02). Patients with late progressive moderate-severe TR had a significantly higher 2-y mortality than those who had moderate-severe TR immediately. CONCLUSIONS: Overall, our study has shown that in the 2 main groups of interest (early moderate-severe TR and progression from nil-mild to moderate-severe TR), TR is more likely to be the result of significant underling graft dysfunction rather than the cause of it.

A novel method to assess valvulo-arterial load in patients with aortic valve stenosis.

INTRODUCTION: Ventricular function in elderly patients with aortic stenosis is impeded both by restricted aortic flow and arterial stiffening. A number of patients continue to have exertional intolerance after relief of aortic valvular obstruction due to unrecognized ventriculo-arterial coupling mismatch. HYPOTHESIS: Quantification of valvulo-arterial load (VAL), using a simultaneous applanation tonometry/cardiac magnetic resonance (CMR) technique, can accurately assess the relative contributions of aortic stiffness and valve gradient in older patients with aortic stenosis. METHODS: Elderly patients with aortic stenosis underwent a simultaneous applanation tonometry/CMR protocol. CMR provided left ventricular volume and aortic flow simultaneously with radial applanation tonometry pressure acquisition. Central aortic pressure was derived by transformation of the radial applanation tonometry waveform. VAL was determined as the relationship of derived aortic pressure to CMR aortic flow in frequency domain (central illustration). RESULTS: Twenty patients (age 80 ±â€Š9 years; 12 males; blood pressure 140/75 ±â€Š20 mmHg) with aortic stenosis on transthoracic echocardiogram (16 severe; mean gradient 45 ±â€Š16 mmHg; aortic valve area 0.8 ±â€Š0.2 cm2) were enrolled. Derived aortic pressure and flow waveforms correlated well with invasive data. Increased VAL was significantly associated with advanced age (P = 0.04) and raised SBP (P < 0.01), irrespective of aortic stenosis severity. CONCLUSION: Difficulties in the measurement and accuracy of ventriculo-arterial coupling means that it is not routinely measured in patients with aortic stenosis. We describe a new noninvasive index that provides an accurate assessment of valvular and arterial load on the left ventricle. VAL may help detect those at risk of ventriculo-arterial coupling mismatch and assist in selection of those most likely to benefit from an invasive procedure.

Effects of modest iron loading on iron indices in healthy individuals.

Intravenous iron administration is typically indicated in individuals who have iron deficiency refractory to oral iron. However, in certain chronic disease states such as heart failure, it may be beneficial to administer intravenous iron to individuals who are not strictly iron deficient. The purpose of this study was to define a dose-response relationship between clinical indices of iron status and modest loading with intravenous iron in healthy, iron-replete participants. This was a double-blind, controlled study involving 18 male participants. Participants were block-randomized 2:1 to the iron and saline (control) groups. Participants in the iron group received 3.75 mg/kg body wt up to a maximum of 250 mg of intravenous iron, once a month for 6 mo, provided that their ferritin remained measured <300 µg/l within the week before a dose was due and their transferrin saturation remained <45%. Otherwise they received a saline infusion, as did the control participants. Iron indices were measured monthly during the study. The pulmonary vascular response to sustained hypoxia and total hemoglobin mass were measured before, at 3 mo (hemoglobin mass only), and at 6 mo as variables that may be affected by iron loading. Serum ferritin was robustly elevated by intravenous iron by 0.21 µg·l-1·mg-1 of iron delivered (95% confidence interval: 0.15-0.26 µg·l-1·mg-1), but the effects on all other iron indices did not reach statistical significance. The pulmonary vascular response to sustained hypoxia was significantly suppressed by iron loading at 6 mo, but the hemoglobin mass was unaffected. We conclude that the robust effect on ferritin provides a quantitative measure for the degree of iron loading in iron-replete individuals.NEW & NOTEWORTHY There has been an increasing interest in administering intravenous iron to patients to alter their iron status. Here, we explore various indices of iron loading and show that in healthy volunteers serum ferritin provides a robust indicator of the amount of iron loaded, with a value of 21 µg/l increase in ferritin per 100 mg of iron loaded.

Elevation of iron storage in humans attenuates the pulmonary vascular response to hypoxia.

Sustained hypoxia over several hours induces a progressive rise in pulmonary artery systolic pressure (PASP). Administration of intravenous iron immediately prior to the hypoxia exposure abrogates this effect, suggesting that manipulation of iron stores may modify hypoxia-induced pulmonary hypertension. Iron (ferric carboxymaltose) administered intravenously has a plasma half-life of 7-12 h. Thus any therapeutic use of intravenous iron would require its effect on PASP to persist long after the iron-sugar complex has been cleared from the blood. To examine this, we studied PASP during sustained (6 h) hypoxia on 4 separate days (days 0, 1, 8, and 43) in 22 participants. On day 0, the rise in PASP with hypoxia was well matched between the iron and saline groups. On day 1, each participant received either 1 g of ferric carboxymaltose or saline in a double-blind manner. After administration of intravenous iron, the rise in PASP with hypoxia was attenuated by ∼50%, and this response remained suppressed on both days 8 and 43 (P < 0.001). Following administration of intravenous iron, values for ferritin concentration, transferrin saturation, and hepcidin concentration rose significantly (P < 0.001, P < 0.005, and P < 0.001, respectively), and values for transferrin concentration fell significantly (P < 0.001). These changes remained significant at day 43 We conclude that the attenuation of the pulmonary vascular response to hypoxia by elevation of iron stores persists long after the artificial iron-sugar complex has been eliminated from the blood. The persistence of this effect suggests that intravenous iron may be of benefit in some forms of pulmonary hypertension.