Circulation Editors’ Picks

Hypertrophy is considered one of the major mechanisms of the myocardium for adapting to hemodynamic overload. More muscle mass provides more contractile elements for generating the extra work required by the overload. In pressure overload of aortic valve stenosis, concentric left ventricular hypertrophy (LVH) normalizes wall stress, a key determinant of ejection performance.1 Afterload is often expressed as wall stress (pressure×radius/thickness). As the pressure term in the numerator increases, it is offset by an increase in the thickness term of the denominator. In this way, the high systolic pressure required to drive blood through even a very stenotic aortic valve can be consistent with normal afterload and normal ejection fraction. See p 3170 Unfortunately, hypertrophy not only provides benefits but also has many pathological consequences. One of these is myocardial ischemia and the attendant angina reported by patients with aortic stenosis despite normal epicardial coronary arteries. The onset of angina greatly increases the risk of sudden death compared with the risk in asymptomatic patients with aortic valve stenosis.2,3 Angina occurs when myocardial oxygen demand exceeds supply. Demand is proportional to heart rate and wall stress, and the latter can be elevated in cases of aortic stenosis when hypertrophy is inadequate to normalize stress.1 After aortic valve replacement, there is marked regression of hypertrophy that may occur over the next several months to years,4 but angina is relieved immediately. Relief of angina immediately after surgery is probably due to the combination of sudden decreased oxygen demand after removal of pressure overload and increased oxygen supply of improved perfusion. However, there are remaining questions about the physiological mechanisms for reduced myocardial oxygen supply (coronary blood flow) in aortic stenosis and its improvement after relief of pressure overload. Specifically, what is it about critical aortic stenosis that is “critical” …

The following are highlights from the new series, Circulation: Cardiovascular Quality and Outcomes Topic Reviews. This series will summarize the most important manuscripts, as selected by the Editor, which have been published in the Circulation portfolio. The objective of this new series is to provide our readership with a timely, comprehensive selection of important papers that are relevant to the quality and outcomes as well as general cardiology audience. The studies included in this article represent the most significant research in the area of valvular heart disease. ( Circ Cardiovasc Quality and Outcomes . 2012;5:-e103.) In recent years, no field of clinical cardiology has experienced a great influx of transformational therapeutic options as has the area of valvular heart disease. Treatment of severe aortic stenosis (AS) has been revolutionized by transcatheter aortic valve replacement (TAVR), which has been shown to improve life expectancy and functional outcomes in patients with inoperable AS1,2 and to have short-term outcomes comparable to surgical aortic valve replacement (AVR) in patients at high perioperative risk.3,4 Analogously, mitral valve disease has been amenable to percutaneous valve replacement,5,6 as well as clipping procedures7 that can substantively reduce severe mitral regurgitation (MR) and improve functional outcomes. Even right-sided heart disease involving valves in pulmonary8,9 and tricuspid10 positions has been treated successfully with endovascular techniques. Yet, even with this growing focus on percutaneous valvular interventions, open surgical techniques remain the dominant treatment strategies and standard of care for most advanced lesions. Surgical valve repair and replacement account for 10% to 20% of all cardiac surgical procedures,11–13 approximately two thirds of which are for AS.11–13 For patients undergoing surgery, there remains considerable debate about risk stratification,14 intraoperative technique,15 and postoperative …

The Deployment of Valve Academic Research Consortium 3 (VARC-3): New Endpoints, Broader Definitions, and Plenty of Unanswered Questions

This article refers to ‘Heart failure with preserved ejection fraction after left-sided valve surgery: prevalent and relevant’ by A.A. Kammerlander et al., published in this issue on pages 2008–2016. It is abundantly clear that clinical outcomes after interventions for left-sided heart valve disease are related to preoperative left ventricular hypertrophy (LVH) and myocardial fibrosis. The timing of treatment is influenced by the detection of changes in left ventricular (LV) geometry and long-axis function and pulmonary vascular resistance, with the goal of avoiding persistent symptoms and irreversible progression to heart failure. It is important to diagnose adverse remodelling preoperatively and to assess its consequences for LV function and reserve, and also important to monitor responses after valve surgery to confirm that hypertrophy is regressing and that function is maintained or improved. Kammerlander et al.1 report that two thirds of their patients attending for follow-up on average 50 months after surgery for aortic or mitral valve disease, fulfilled diagnostic criteria for heart failure with preserved ejection fraction (HFpEF). More than half of the patients were in atrial fibrillation and their natriuretic peptide levels were very high, exceeding levels usually observed in patients with HFpEF alone. More importantly, only 12.5% of them had been diagnosed to have heart failure, so their symptoms and need for increased treatment were unrecognized. And most importantly, patients with this syndrome had an increased mortality that was similar to patients with heart failure with reduced ejection fraction (HFrEF), who had been recognized. Over a follow-up of 7 years their risk of dying was 1.8 times higher than patients who had also had valve interventions but who did not have heart failure. Their study serves as a timely reminder that full recovery after valve surgery cannot be assumed, so careful assessment and continuing close supervision are indicated. Aortic stenosis (AS) is mostly a disease of the elderly. Hypertension is common in older people. Hypertension causes LVH. Many patients with AS develop concentric LVH as a compensatory response to their outflow obstruction, that tends to normalize wall stress, but they may also be hypertensive. In the SEAS study of 1616 patients, hypertension was associated with a 56% higher rate of ischaemic cardiovascular events and a two-fold increased mortality, independently of the severity of AS or of abnormal LV geometry.2 Some patients who have a normal LV ejection fraction and are diagnosed to have normal-flow low-gradient AS may have predominant hypertensive heart disease.3 Even some patients diagnosed to have low-flow low-gradient AS may instead have a combination of HFpEF with mild or moderate AS. It can be difficult to discriminate between these since both may impair stroke volume reserve, but hypertension with a wide pulse pressure indicative of stiff central conduit arteries and impaired ventricular–arterial coupling is at least a contributory cause of LVH in many patients. Volume and pressure overload from aortic regurgitation lead to diastolic dysfunction with increased myocardial stiffness that persists late after valve surgery.4 Elderly patients with severe mitral regurgitation may have coexisting hypertension that contributes to the progression of disease and development of eccentric LVH. Chronic LV dilatation may exacerbate secondary mitral regurgitation. Thus there are many overlaps between the patterns of LV and left atrial (LA) remodelling caused by hypertensive heart disease and by heart valve disease, with particular patterns for each pathology. The most recent European Society of Cardiology (ESC) consensus recommendations stated that “HFpEF can be suspected if there is … no significant heart valve disease” and that “HFpEF ‘masqueraders’ such as heart valve disease … need to be excluded.”5 Heart valve disease affects not only LV mass but also most of the other echocardiographic measurements that contribute to the HFA-PEFF score. For example, the septal e′ may be reduced if there is interstitial fibrosis in AS, or increased if there is volume overload caused by aortic or mitral regurgitation. The E/e′ ratio may be useful in patients with AS but unreliable in those with mitral valve disease.6 Long-axis function (measurable as LV global longitudinal strain, another component of the score) can be reduced after cardiac surgery because of pericardial adhesions. Atrial fibrillation secondary to LA enlargement, irrespective of whether or not there is coincidental heart failure, contributes to high levels of natriuretic peptides. Natriuretic peptide levels are also increased after cardiac surgery. In mitral stenosis the left atrium is enlarged and there may be post-capillary pulmonary hypertension, both changes that can also occur in HFpEF. Thus, it is inappropriate either to describe patients as having ‘HFpEF’ due to heart valve disease, or to diagnose that a patient with valve disease has coexisting HFpEF without first undertaking a careful search for specific haemodynamic sequelae of surgery. That does not invalidate the observation that patients with valve disease may have an equivalent phenotype — with LVH, diastolic dysfunction, longitudinal systolic dysfunction, impaired LV functional reserve, LA dilatation, and secondary pulmonary hypertension — that is equally deserving of effective treatment. Unfortunately, Kammerlander et al. did not have data to report preoperative findings in their patients either about the severity of AS or other valve diseases or about the degree of LVH, but it is more likely that the phenotype at follow-up was persisting rather than new. The investigators applied diagnostic criteria from the ESC guidelines of 2017, which for HFpEF were rather general. The precise diagnostic label, however, is less important than recognition of its components and their consequences — especially hypertrophy. After aortic valve replacement (AVR) there is less regression of LVH in patients who have poorly controlled hypertension, and persisting LVH predicts poor outcomes including heart failure. Earlier observations from the surgical literature have been confirmed after transcatheter aortic valve implantation, for example in 1434 patients from the PARTNER trials in whom less regression of LVH at 1 year was associated with increased mortality.7 The risk ratio for those with severe LVH at 1.77 was almost identical to that reported by Kammerlander et al. for their ‘HFpEF’ phenotype,1 so in essence their study reinforces the known prognostic significance of hypertension, LVH, atrial fibrillation, LA volume, and natriuretic peptide levels after valve surgery. Risk factors for the persistence of LVH include a body mass index ≥30 kg/m2 before AVR8 and either metabolic syndrome or diabetes.9 There is less regression if the ascending aorta is heavily calcified10 or if postoperative renal function is moderately impaired.11 Jang et al.12 reported that LVH correlated most closely with global LV afterload and valvuloarterial impedance. It is notable that all these factors are also risk factors for HFpEF5; a common mechanism would be that they all increase arterial stiffness and augment end-systolic loading. The use of warfarin after mechanical valve replacement is also relevant: since it inhibits the matrix Gla protein, which is itself an inhibitor of vascular calcification, it can increase arterial stiffness and pulse pressure13 which would promote LVH. A secondary benefit from optimal control of hypertension after valve interventions could be a reduction in systemic embolism. After AVR, postoperative hypertension had an odds ratio of 8 for ischaemic cerebrovascular events, while other risk factors included postoperative smoking and diabetes.14 In the Cardiff Embolic Risk Factor Study, which enrolled patients after all heart valve operations, hypertension and diabetes contributed to a score that strongly predicted systemic embolism.15 Replacement fibrosis within the LV myocardium is probably irreversible but interstitial fibrosis can regress after AVR.16 Diffuse fibrosis as a consequence of chronic maladaptive LVH correlates with diastolic dysfunction. Relative expansion of the extracellular volume fraction, as a marker of diffuse fibrosis, appears more pronounced in women than in men at comparable degrees of pressure overload.17 Patients who undergo valve interventions are typically elderly with multiple comorbidities. They may have hypertension, atherosclerotic diseases and arrhythmias as well as heart valve disease, so clinical responsibilities do not end with the intervention (Figure 1). In the study by Kammerlander et al., overall mortality after 83 ± 39 months was 34%.1 As well as individual treatment directed to the primary target of hypertension with LVH, there is a need for more evidence to guide therapeutic decisions. Since most patients are now enrolled in registries, there is scope for large registry-based randomized trials. With a factorial or adaptive design they could evaluate both established and new drugs that are considered for patients with HFpEF. Well-characterized age-matched control groups would be essential. These comments have mostly concerned AS, which was the dominant lesion in 62% of the patients in the study of Kammerlander et al. In a randomized study of 114 patients after AVR, candesartan reduced LV mass and LA volume and increased LV long-axis systolic function; the changes were unrelated to systolic blood pressure or pulse pressure which were similar to controls.18 In an observational study of 200 patients with LVH who received a bioprosthetic AVR, the probability of complete LV mass regression by 1 year postoperatively was increased by an odds ratio of 3.4 in patients who had been prescribed a beta-blocker or calcium-channel blocker.19 In the OCEAN-TAVI registry of 1215 subjects, blockade of the renin–angiotensin system was associated with greater reduction of LV mass and a lower mortality at 2 years (by >50%).20 Until more evidence is available from prospective trials about the efficacy of specific pharmacological interventions, the main conclusion that may be derived from the study by Kammerlander et al. is that we should continue to search for more precise diagnostic criteria that would qualify patients for surgery early enough to prevent irreversible adverse sequelae of preoperative LVH and myocardial fibrosis, and which would justify the risks of an earlier surgical procedure. Better diagnostic criteria will be specific for each valve lesion, and all patients may have classical HFpEF without it being caused by their valve disease. Conflict of interest: none declared.

Background: In the randomized Placement of Aortic Transcatheter Valves (PARTNER) trial, the NYHA functional class was improved at 1 year in both the transcatheter aortic valve replacement (TAVR) and the surgical bioprosthetic aortic valve replacement (SAVR). However, more patients in TAVR than in SAVR had a reduction in symptoms at 30 days. As part of a single center PARTNER trial experience, we compared left ventricular (LV) and left atrial (LA) function in patients after TAVR with those with SAVR for the treatment of severe aortic valve stenosis at one month follow-up. Methods and Results: A total of 83 severe aortic valve stenosis patients with preserved LV systolic function (EF > 40%) and without moderate or severe valvular regurgitation were included in the study: 52 patients underwent TAVR and 31 patients underwent SAVR. Echocardiographic parameters were similar between the two groups. In each group, LVEF and peak early diastolic mitral annular velocity (e') increased significantly at one month follow-up. The ratio of peak S-wave to D-wave from pulmonary vain flow (PVS/PVD) was higher in the TAVR group as compared with the baseline, while there is no significant difference in SAVR group. LV end-diastolic dimension (LVEDD), left atrial area (LAA), the ratio of early transmitral flow velocity (E) to e' (E/e') and LV mass index significantly decreased as compared with baseline in each group (Table 1). There were no significant differences between the two groups in LVEDD, EF, LAA, PVS/PVD, e', E/e' and LV mass index one month after the procedure. At one month follow-up, however, the changes (post minus pre) of LAA, PVS/PVD, e' and E/e' were significantly larger in the TAVR group than the SAVR group (Table2). Conclusion: In patients with severe aortic stenosis, both TAVR and SAVR improved LV systolic and diastolic function and LA function one month after intervention. In particular, the improvement after TAVR appeared to be greater than after SAVR.

2012 ACCF/AATS/SCAI/STS Expert Consensus Document on Transcatheter Aortic Valve Replacement: Developed in collaboration with the American Heart Association, American Society of Echocardiography, European Association for Cardio-Thoracic Surgery, Heart Failure Society of America, Mended Hearts, Society of Cardiovascular Anesthesiologists, Society of Cardiovascular Computed Tomography, and Society for Cardiovascular Magnetic Resonance

Self-Expanding Versus Balloon-Expandable Valve: Are We at the Cusp of Delivering a Perfect Transcatheter Aortic Valve?

Transcatheter Aortic Valve Implantation During the COVID-19 Pandemic

<i>Circulation: Cardiovascular Imaging's</i> Editors' Picks

Developmental efforts to achieve percutaneous catheter-based therapies for cardiac valve repair and replacement have advanced rapidly over the past several years. A variety of methods to treat mitral regurgitation (MR) and to replace aortic and pulmonic valves have already been successfully employed in patients. These innovative clinical transcatheter valve therapies were anticipated more than a decade ago by creative experimentalists who helped develop predicate techniques in animal models. For example, in 1992, a catheter-delivered ball-in-cage prosthetic aortic valve was implanted in a canine model by Pavcnik1 and a stent-mounted bioprosthetic valve was placed by Andersen, who used a retrograde transarterial approach in a swine model.2 Clearly, the catheter-based technologies used in clinical studies today in patients with aortic stenosis were derived from the fusion of known successful aortic valve replacement (AVR) surgical devices and adaptive interventional modalities, first studied in experimental animal models. Similarly, approaches for transcatheter treatment of MR have also borrowed heavily from preexisting and accepted surgical techniques, such as the edge-to-edge leaflet coaptation technique and reduction ring mitral annuloplasty.3 Importantly, recognition that the coronary sinus parallels the mitral annulus has spurred unique catheter-based transvenous approaches to treat MR by indirectly reducing mitral annular dimensions.4 Because many of the new percutaneous approaches to valve therapy have been developed by surgeons, a collaboration has emerged between thoughtful surgeons and interventionalists, combining skill sets and experiences to accelerate the developmental pathways of less-invasive transcatheter valve therapies. Growing recognition exists that percutaneous alternatives to surgical therapies are required in some patient subgroups with valvular heart disease. Among patients with either mitral and/or aortic valve disease, an expanding population of elderly patients with significant comorbidities may benefit from traditional surgical methods, but these methods are associated with unacceptable perioperative mortality or prolonged postoperative recoveries. In the EuroHeart Survey …

<i>Circulation</i> Editors’ Picks

Case presentation: A 66-year-old man is referred to a cardiologist for the evaluation of a heart murmur. The patient claims to be entirely asymptomatic, although his wife notes that he has decreased his physical activity over the past two years because he is “getting old.” At physical examination, his blood pressure was 120/70 mm Hg; pulse, 80 bpm; respiration, 13 breaths per minute; and temperature, 99.0°F. Cardiovascular examination revealed normal central venous pressure. His carotid upstrokes were reduced in volume and delayed in upstroke. Cardiac examination revealed a forceful sustained apical impulse in its normal position. There was a 3/6 late-peaking systolic ejection murmur heard at the right upper sternal border radiating to the neck. The rest of the physical examination was unremarkable. Echo-Doppler evaluation revealed an ejection fraction of 0.60, a left ventricular free wall thickness of 1.3 cm, and a peak transaortic flow velocity of 4.5 m/s. How should this patient be managed? Should he undergo aortic valve replacement now? Should he undergo longitudinal follow-up to monitor progression of his aortic stenosis? Over the past 40 years, diagnostic techniques, substitute cardiac valves, and valve implantation surgery have undergone continued improvement, reducing the risk of the valve replacement and enhancing its benefits. Thus, the risk-benefit analysis of valve surgery has tilted in favor of increasingly early intervention for valve disease. The following is a summary incorporating this concept into the current strategy for managing patients with aortic stenosis such as the one described above. The patient with severe aortic stenosis who presents with symptoms represents the most straightforward management strategy for the disease. Survival is nearly normal until the classic symptoms of angina, syncope, or dyspnea develop.1 However, only 50% of patients who present with angina survive 5 years, whereas 50% survival is 3 years for patients who …

Transcatheter aortic valve replacement valve-in-valve: Future implications for the surgeon

Background Global longitudinal strain (GLS) has incremental value in assessing left ventricular (LV) function in patients with severe aortic stenosis (AS). Long-standing AS causes LV hypertrophy which predisposes to increased cardiac morbidity and mortality. The recent development of transcatheter aortic valve implantation (TAVI) device for treatment of severe symptomatic AS, offers an option for high risk patients. Objectives Our aim was to investigate the correlation between the time elapsed after performing a TAVI procedure and the LV GLS by Speckle tracking echocardiography (STE) and its correlation with progressive degree of regression in LV mass (LVM) by transthoracic echocardiography (TTE). Methods TTE was performed on 54 patients with severe AS who underwent TAVI procedure. TTE was performed at baseline (before the procedure) and then at 3 months and 6 months post TAVI. GLS was calculated for every patient from STE of the three apical views (apical 4, apical 2 and apical long axis views). The LV muscle volume was calculated by subtraction of LV pericardial volume from LV endocardial volume using biplane Simpson's formula. LVM was then calculated by multiplying LV mass volume by muscle density (1.05). Results The study included 54 patients with severe AS (average PG =79.5 mmHg and average mean gradient 40.5 mmHg), with a mean age of 79±10 years and 46 were male. All patients underwent TAVI and average mean gradient post TAVI was 7 mmHg. The mean ± SD of GLS were −15.3±2.0, −15.9±1.7 and −17.2±1.8 for STE obtained at baseline, 3- and 6-months post TAVI, respectively. There was significant difference in LV GLS when comparing baseline measurements with measurements obtained at both 3 months {mean difference ± SD (MD±SD) was 0.57±0.7 (p&amp;lt;0.001)} and at 6 months post TAVI was 1.8±0.8 (p&amp;lt;0.0001). There was significant difference when comparing LV GLS measurements at 3- and 6- months post TAVI MD±SD was 1.2±0.65 (p&amp;lt;0.001). The mean±SD of LVM was 118.5±31, 110.5±29.2 and 101.1±26.4 at baseline, 3- and 6-months post TAVI, respectively. There was significant difference between baseline and 3 months measurement of LVM, MD±SD is 7.6±6.0 (p&amp;lt;0.001). There was significant difference between baseline and 6 months measurement of LVM, MD±SD was 17.0±10.5 (p&amp;lt;0.0001). In addition, there was significant difference of LVM calculation at 3 and 6 months with MD±SD of 9.4±7.9 and (P&amp;lt;0.001). Conclusions In patient with severe AS that underwent TAVI, there is short term continues significant improvement of LV GLS by STE. This could be attributed to relieving the pressure overload and regression of LVM over time. Decreasing LV hypertrophy and increasing LV GLS on the short term indicate high efficacy of TAVI procedure and subsequently improving patient prognosis and quality of life. Funding Acknowledgement Type of funding source: None

Received October 26, 2004; revision received January 13, 2005; accepted February 4, 2005. Calcific aortic valve disease is a slowly progressive disorder with a disease continuum that ranges from mild valve thickening without obstruction of blood flow, termed aortic sclerosis, to severe calcification with impaired leaflet motion, or aortic stenosis (Figure 1). In the past, this process was thought to be “degenerative” because of time-dependent wear-and-tear of the leaflets with passive calcium deposition. Now, there is compelling histopathologic and clinical data suggesting that calcific valve disease is an active disease process akin to atherosclerosis with lipoprotein deposition, chronic inflammation, and active leaflet calcification. The overlap in the clinical factors associated with calcific valve disease and atherosclerosis and the correlation between the severity of coronary artery and aortic valve calcification provide further support for a shared disease process. Figure 1. Gross specimen of minimally diseased aortic valve (left) and severely stenotic aortic valve (right). In the severely stenotic valve, there are prominent lipocalcific changes on aortic side of valve cusps (arrow), with sparing of commissures. ### Anatomy of Normal Aortic Valve The normal aortic valve comprises 3 layers. The ventricularis, on the ventricular side of the leaflet, is composed of elastin-rich fibers that are aligned in a radial direction, perpendicular to the leaflet margin. The fibrosa, on the aortic side of the leaflet, comprises primarily fibroblasts and collagen fibers arranged circumferentially, parallel to the leaflet margin. The spongiosa is a layer of loose connective tissue at the base of the leaflet, between the fibrosa and ventricularis, composed of fibroblasts, mesenchymal cells, and a mucopolysaccharide-rich matrix. These layers work in concert to provide tensile strength and pliability for decades of repetitive motion. ### Early Lesion of Aortic Sclerosis Histopathologic studies of aortic sclerosis show focal subendothelial plaquelike lesions on the aortic side of the leaflet that extend to the adjacent fibrosa layer. Similarities to …