Why angina in aortic stenosis with normal coronary arteriograms?

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 …

Cardiac hypertrophy is a morphological adaptive increase in myocardial mass in response to chronic work overload and is a common clinical finding affecting 23% of men and 33% of women over the age of 59 years [1]. Pressure or volume overload on the myocardium results in an increase in myocardial wall stress and hypertrophy may be seen as an attempt to normalise wall stress and oxygen demand. Although initially protective, the increased myocardial mass requires an increase in coronary blood flow to maintain function; indeed, ventricular hypertrophy may be associated with myocardial ischaemia even with angiographically normal coronary arteries [2–4]. Left ventricular hypertrophy (LVH) significantly increases the risk of myocardial infarction, congestive heart failure and sudden cardiac death [5–7]. It is also associated with a greater prevalence of cardiac arrhythmias [8] and is an important risk factor for cardiac morbidity and mortality [9–10]. Understanding the potential mechanisms for these adverse effects has been the focus of much interest in recent years.

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Transcatheter aortic valve replacement (TAVR) has revolutionized the treatment of patients with severe aortic stenosis who are at high risk for traditional surgical intervention.1,2 As the technology matures and experience grows, the applicability of TAVR to lower risk populations is likely and is already being explored.3 These patients often present with chest pain or exertional dyspnoea in the context of varying degrees of coronary artery disease. An understanding of how the aortic valve affects coronary hemodynamics is becoming increasingly clinically relevant in determining how to manage this coexisting coronary disease. See Article by Wiegerinck et al Creating a model of aortic stenosis is challenging. The pressure loading of the ventricle and coronary arteries varies according to the location of the stenosis. Stenosis at the level of the aortic valve is anatomically below coronary artery inflow; this results in increased afterload of the left ventricle but reduces coronary perfusion pressure. Relief of the stenosis therefore results in an acute reduction in left ventricular end-diastolic pressure, and in most cases, it results in an increase in coronary perfusion. This differs from the traditional systemic hypertension model often generated experimentally in animal models in which a restrictive band is placed around the aorta.4 In such cases, the stenosis is positioned in the aorta distal to coronary artery inflow; this results in an increase in both left ventricular end-diastolic pressure and coronary perfusion. After removal of the aortic band, both left ventricular end-diastolic pressure and coronary perfusion fall; as a result, the …

In adults with valvular aortic stenosis (AS), valve replacement is recommended in the presence of symptoms and severely reduced aortic valve area (AVA).1 In such patients, valve replacement improves symptoms and survival, even in the setting of left ventricular (LV) dysfunction. LV dysfunction in severe AS is usually due to afterload mismatch; valve replacement relieves the afterload excess imposed by the stenotic valve and improves LV performance. 2 However, a subset of patients with “ severe” AS, LV dysfunction, and low-transvalvular gradient has been reported to have a relatively high operative mortality and poor prognosis.2–4⇓⇓ This clinical scenario has been termed “low-flow, low-gradient AS.” Accurate assessment of AVA in such patients is difficult because (1) calculated AVA is directly proportional to forward stroke volume, and (2) the Gorlin constant varies at low-flow states. 5–7⇓⇓ Some patients with low-flow, low-gradient AS have a reduced AVA as a result of inadequate forward stroke volume rather than anatomic stenosis, a situation analogous to reduced anterior mitral leaflet excursion in dilated cardiomyopathy where there is not enough forward flow to fully open the valve. For example, Cannon et al 8 showed that some patients with low-gradient AS were found to have only mild AS at surgery despite a Gorlin AVA indicating critical AS. Obviously, surgical therapy is unlikely to benefit such patients because their primary pathology is a cardiomyopathy. On the other hand, patients with severe anatomic AS may benefit from valve replacement despite the increased operative risk associated with a low-flow, low-gradient hemodynamic state. The recent American College of Cardiology/American Heart Association (ACC/AHA) guidelines for managing valvular heart disease recommends hemodynamic evaluation of low-flow, low-gradient AS using dobutamine echocardiography to distinguish patients with fixed anatomic AS from those with flow-dependent (“ relative”) AS in patients with LV …

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 …

Coronary flow reserve improves after aortic valve replacement for aortic stenosis: an adenosine transthoracic echocardiography study

Robotic aortic valve replacement

Aortic valve replacement surgery is the only available treatment option able to improve survival in patients with symptomatic and severe aortic valve stenosis. Without surgical intervention, patients with symptomatic dyspnea and severe aortic valve stenosis have a median survival less than 2 years. In an ideal, patient-centered healthcare system, the decision whether to undergo risky yet potentially life-prolonging surgery should not only reflect judicious application of the evidence of safety and efficacy of the surgery, but it also should be consistent with the patient’s clinical and personal contexts, and their goals, values, and preferences for life and healthcare. Article see p 533 The report by Bach et al1 is the latest in their series of investigations to uncover why cardiac valve replacement surgery is underused among eligible candidates. In this report, they seek explanations among patient, clinician, and hospital-level characteristics and suggest the following hypothesis: clinicians, particularly cardiologists, are making apparently inconsistent judgments as to which patients should be referred to cardiac surgeons for consideration of aortic valve replacement. Among 191 patients with severe aortic valve stenosis who did not undergo cardiac surgery, a cardiologist evaluated 182 (95%), but referred only 57 (30%) to a cardiac surgeon. In this editorial, we will place this finding in the context of the evolving field of shared decision-making and suggest how this focus could improve the quality of care delivered to patients with valvular heart disease. Shared decision making is a 3-step process.2 The first step involves knowledge transfer. In its idealized form, shared decision making requires symmetrical and bidirectional exchange of information between patients and clinicians. This exchange aims to identify and distinguish the available options under consideration, including the option of no treatment. The other 2 steps require the patient and clinician to (1) actively engage in deliberating (ie, …

Mitral regurgitation (MR) is frequently associated with aortic stenosis. Previous reports have shown that coexisting mitral insufficiency can potentially regress after aortic valve replacement. This study sought to assess the frequency and severity of MR before and after aortic valve replacement for aortic stenosis and to define the determinants of its postoperative evolution. For this purpose, 30 adult patients referred for aortic valve surgery underwent pre- and postoperative transthoracic and transesophageal echocardiography and color Doppler examination. Mean preoperative left ventricular ejection fraction was 57 +/- 16% and remained unchanged postoperatively. Preoperative MR was usually mild to moderate and correlated with aortic stenosis severity and left ventricular systolic dysfunction. The color Doppler mitral regurgitant jet area significantly decreased during the postoperative period (p = 0.016) as left ventricular loading conditions returned to normal, suggesting an early decrease of the functional part of MR. On the other hand, the mitral regurgitant jet width at the origin remained unchanged. Statistical analysis found pulmonary artery pressure (p = 0.02) an d indexed left ventricular mass (p = 0.009) to be preoperative predictive factors of postoperative MR improvement. Predictive factors of postoperative MR severity were left atrial diameter (p = 0.02), pulmonary artery pressure (p = 0.003), and the presence of mitral calcifications (p = 0.004). In our cohort of patients with normal left venticular ejection fraction, the majority of moderate MR, associated with severe aortic stenosis, regresses early after aortic valve replacement. Mitral calcifications and/or left atrial dilation seem to be predictive factors of fixed MR.

Transcatheter aortic valve replacement (TAVR) has recently emerged as a therapeutic option for patients with severe aortic stenosis who are considered inoperable.1 To avoid potential complications related to this novel procedure (such as coronary artery obstruction or perivalvular leakage), detailed information on the aortic valve anatomy is critically important.1,2 Multislice computed tomography (MSCT) enables a comprehensive 3D assessment of aortic valve anatomy and, particularly, the extent and location of valve calcifications, one of the reasons for inappropriate deployment of the valved stent together with the bicuspid anatomy.3 After TAVR, the positioning and deployment of the valve prosthesis can be evaluated by this imaging technique. This report concerns a 54-year-old woman with symptomatic bicuspid aortic valve stenosis (aortic valve area, 0.9 cm2). Comorbidity included hypertension and hypercholesterolemia. Importantly, 2 years earlier, the patient experienced a cerebrovascular accident with severe consequences that determined a high risk for cardiac surgery. Consequently, the …

Background Aortic valve calcification (AVC), as measured by gold-standard computed tomography (CT) Agatston score, provides an anatomic assessment of aortic stenosis (AS) severity and is a key predictor of AS progression and need for valve replacement. AVC detection and quantification from transthoracic echocardiography (TTE) could expand AS early diagnosis and risk stratification, currently limited by CT availability and radiation exposure. Methods A multi-view video-based deep learning framework was developed using 1166 TTE aortic valve videos from 187 TTE studies acquired in 110 patients with available AVC score by CT. EchoAVC architecture includes a feature extraction model followed by a quality-aware model that aggregates video-level information to obtain patient-level predictions for AVC detection and quantification (score). The framework was validated internally with 173 TTE studies from 86 patients across seven centres, and externally using 430 TTE studies from 280 patients across four different centres. The associations between EchoAVC estimations and AS severity, progression, and need for aortic valve replacement were examined. Results EchoAVC demonstrated excellent performance in AVC detection (AUROC 0.98, accuracy 94.4%), and quantification (R = 0.64) in the external multi-centre testing set. EchoAVC score was correlated with echocardiographic AS severity descriptors, including aortic valve mean pressure gradient (ρ = 0.749) and peak velocity (ρ = 0.757), and predicted future increase in mean pressure gradient (ρ = 0.382), peak velocity (ρ = 0.433) and calcium score by CT (ρ = 0.650). In 361 patients followed for a median of 3.8 years, 139 underwent aortic valve replacement. Baseline presence and extent of AVC as predicted by EchoAVC showed strong risk-stratification power for aortic valve replacement, remarkably in line with those obtained by CT, and incremental over TTE AS descriptors. EchoAVC was further tested in routine clinical practice images, confirming strong associations with AS severity and progression, including stratification for incident AS in previously unaffected individuals (p&lt;0.001). Conclusions EchoAVC enables accurate and non-invasive detection and quantification of AVC, offering substantial diagnostic and prognostic value for aortic stenosis progression and need for valve replacement. This technique holds promise as a scalable tool for early detection and clinical management of aortic valve stenosis. Clinical Perspective What Is New? * Aortic valve calcification can be detected and quantified on standard, two-dimensional transthoracic echocardiography * EchoAVC score is associated with echocardiographic metrics of aortic stenosis severity * EchoAVC predicts progressive increase in aortic stenosis severity and need for aortic valve replacement What Are the Clinical Implications? * This openly available deep learning framework can be used to estimate aortic valve calcium in patients at risk of or presenting aortic stenosis to predict aortic stenosis progression * EchoAVC may help identify patients likely to have high aortic valve calcium and prioritize them for confirmatory CT assessment, thereby supporting earlier identification of calcific aortic valve disease in clinical pathways.

Objective To evaluate left ventricular myocardial function alternation by three-dimensional speckle tracking imaging (3D-STI) after surgical aortic valve replacement (AVR) in severe aortic stenosis (AS) patients with preserved left ventricular ejection fraction (LVEF), and discuss its clinical value. Methods Forty patients with severe aortic stenosis who were hospitalized or outpatient in Nanjing First Hospital Affiliated to Nanjing Medical University during the period of October 2014 to October 2016 (AS group), and forty healthy volunteers (normal control group) were enrolled in this study. Normal control group underwent conventional echocardiography and 3D-STI measurement, while the AS group underwent conventional echocardiography and 3D-STI measurement at preoperative, 1 week postoperative and 3 months postoperative, then we obtained left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), interventricular septum thickness diameter (IVSd), left ventricular posterior wall thickness diameter (LVPWd), left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), global area strain (GAS) strain and 3D-strain. The independent sample t test was used to compare the difference of conventional ultrasound parameters and 3D-STI parameters between AS preoperative patients and healthy controls, AS patients at 3 months postoperative and healthy controls. The single factor analysis of variance was used to compare the difference of conventional ultrasound parameters and 3D-STI parameters in severe patients at preoperative, 1 week postoperative and 3 months postoperative. LSD-t test was used to compare in different AS groups. Results Compared with normal control group, IVSD, LVPWD and GCS of severe AS patients increased significantly (t=13.824, 11.298 and -6.584, all P<0.001), GLS, GRS and 3D-Strain decreased significantly (t=10.221, -6.237 and -5.674, all P<0.001), LVEDD, LVESD and GAS had no significant difference. Compared with preoperative AS patients, LVEF, GLS, GAS and GCS decreased significantly (t=-2.205, -2.093, -2.034 and -3.152, all P<0.05 or 0.01) at 1 week postoperative, LVEDD, LVESD, IVSD, LVPWD, GRS and 3D-strain had no significant difference at 1 week postoperative; GLS, GRS and 3D-strain increased significantly (t=5.446, -4.923 and -4.388, all P<0.05 or 0.01) at 3 months postoperative, GCS, IVSD and LVPWD decreased significantly (t=-3.988, 4.794 and 4.211, all P<0.05 or 0.01) at 3 months postoperative, LVEDD, LVESD, LVEF and GAS had no significant difference at 3 months postoperative. Compared with AS patients at 1 week postoperative, LVEF, GLS, GRS, GAS and 3D-strain increased significantly (t=-2.631, 7.383, -4.719, 2.923 and -4.154, all P<0.05 or 0.01) at 3 months postoperative, GCS, IVSD and LVPWD decreased significantly (t=-2.109, 4.747 and 4.323, all P<0.05 or 0.01) at 3 months postoperative. But in AS patients at 3 months postoperative, IVSD, LVPWD, GLS and GCS were still higher than those of normal control group (t=9.809, 7.066, 4.752 and -2.553, all P<0.001 or <0.05), LVEDD, LVESD, LVEF, GRS, GAS and 3D-strain had no significant difference. Conclusion The alternation of left ventricular myocardial function have a certain characteristic before and after aortic valve replacement in severe aortic stenosis patients with preserved LVEF, and 3D-STI can evaluate it more accurately. Key words: Three-dimensional speckle tracking; Left ventricular ejection fraction; Aortic valve stenosis; Aortic valve replacement; Myocardium

The Western Washington Intracoronary Streptokinase randomized trial1 first demonstrated that intracoronary thrombolytic therapy improved survival for patients presenting within 12 hours of symptom onset of acute myocardial infarction (MI). Perhaps equally important, this invasive study demonstrated that in-hospital and long-term survival was greatly improved in patients with patent infarct-related arteries.2 These observations ushered in the modern era of reperfusion therapy, and they also firmly established the concept that achieving arterial patency was the predominant mechanism for the prognostic benefit of thrombolytic agents. Numerous trials since then have validated this open-artery hypothesis.3 4 5 In the early 1990s, Ross et al6 definitively established the relationship between prompt reinstitution of flow, improved myocardial salvage, and survival. Anderson et al7 clearly demonstrated that antegrade flow, as defined by the Thrombolysis in Myocardial Infarction (TIMI) criteria, can differentiate different levels of antegrade flow, with different prognostic implications. Although TIMI flow grades seem to segregate effective from ineffective flow, this analysis is only a qualitative measure that can be subject to bias and interlaboratory variability. Gibson et al8 further refined angiographic flow quantitation using corrected TIMI frame counts. This method of analysis quantitates angiographic contrast velocity measures and decreases variability. Currently, arterial patency is the gold standard for assessing the efficacy of different reperfusion protocols. Refinements in the quantitation of degrees of arterial patency have led to improvements in the prognostic value of this measure. It has, however, become increasingly apparent that contrast velocity alone does not adequately define the level of microvascular perfusion or predict the extent of return of myocardial function after successful reperfusion therapy. Coronary angiography remains a crude means to assess myocardial perfusion after infarction, and it is clear that infarct artery patency is not equivalent to the reestablishment of myocardial tissue perfusion. With the …

Coronary flow reserve is impaired in asymptomatic patients with aortic stenosis and has a prognostic value. We investigated whether the type II diabetes mellitus additionally impairs microvascular circulation assessed by coronary flow reserve in patients with asymptomatic severe aortic stenosis, normal left ventricular ejection fraction and nonobstructed coronary arteries. A total of 128 patients, mean age of 66.35 ± 10.51 (58.6% males), with severe aortic stenosis and normal left ventricular ejection fraction were enrolled in this study. Patients with diabetes mellitus, those who were treated for diabetes mellitus or had documentation confirming the diagnosis of diabetes mellitus, were considered. All patients underwent coronary angiography and had no obstructive coronary disease (defined as having no stenosis >50% in diameter), standard transthoracic Doppler-echocardiographic study and adenosine stress transthoracic echocardiography for coronary flow reserve measurement. Diabetes mellitus was present in 26 patients (20.31%). There was no significant difference in aortic stenosis severity between diabetic and non-diabetic patients [aortic valve area (0.81 ± 0.18 vs 0.85 ± 0.15 cm(2)) and Vmax (4.20 ± 0.57 vs 4.21 ± 0.48 m/s)]. Mean coronary flow reserve in diabetic patients was 1.98 ± 0.48, while mean coronary flow reserve in non-diabetic patients was 2.64 ± 0.54 (p < 0.01). Diabetes mellitus was independent predictor of coronary flow reserve [B = -0.636, 95% confidence interval (-0.916 to -0.368), p < 0.001]. Diabetes mellitus additionally impairs coronary microvascular function in asymptomatic patients with severe aortic stenosis and nonobstructed coronary arteries.