Author Correction: Pressure gradient vs. flow relationships in patients with symptomatic valvular aortic stenosis - PREFLOW.

There has been a striking evolution in the role of the cardiac catheterization laboratory over the past decades.1 In the 1950s and 1960s, hemodynamic assessment in the cardiac catheterization laboratory was essential for understanding the physiology and pathophysiology of patients with cardiovascular diseases. With the development of surgical interventions to treat patients with valvular and congenital heart disease, it became necessary for the cardiac catheterization laboratory to provide an accurate hemodynamic assessment, laying out a therapeutic road map. Nearly all patients who had open heart surgery underwent a complete hemodynamic catheterization before surgery. In the 1980s and 1990s, the evolution of 2-dimensional echocardiography and Doppler echocardiography provided an alternative noninvasive approach for the assessment of both cardiac anatomy and hemodynamics in patients with structural heart disease.2 By measuring blood flow velocities noninvasively, Doppler echocardiography was able to provide information on volumetric flow, intracardiac pressures, pressure gradients, and valve areas, as well as diastolic filling of the heart. Furthermore, noninvasive studies could be repeated easily, allowing the practitioner to follow the progress of his/her patient's condition longitudinally. At the same time, there was growing emphasis on coronary angiography for defining epicardial coronary disease with the subsequent development of interventional approaches for coronary disease with catheter-based therapies. As the major focus in the catheterization laboratory shifted to the diagnosis and treatment of the patient with acute and chronic coronary artery disease, the hemodynamic assessment of patients with structural heart disease was left to the noninvasive echocardiographic laboratory. As a consequence, many cardiac catheterization laboratories provided neither the training nor the expertise to assess hemodynamics properly. However, the advent of procedures such as balloon valvotomy, percutaneous valve implantation, and septal ablation has revived interest in structural heart disease and provided the invasive cardiologist with an armamentarium to treat patients who previously …

Management of aortic stenosis, particularly with preserved left ventricular ejection fraction (LVEF) and discordant or borderline echocardiographic findings, remains challenging, both in assessing the true severity of stenosis and in isolating the valvular contribution to symptoms amidst comorbid conditions. This study evaluates the feasibility and physiological insight obtained from invasive pressure measurements across the aortic valve at rest and during exercise in symptomatic patients with aortic stenosis (AS). This prospective cross-sectional study included patients with symptomatic high-gradient severe, low-gradient severe, and moderate aortic stenosis. They underwent invasive pressure gradient measurements across the aortic valve (pressure catheters in the left ventricle and ascending aorta) with concurrent right heart catheterization at rest and during peak supine bicycle exercise. Of 28 patients included, invasive measurements during exercise were feasible in 25 patients. Overall, exercise induced increases in aortic valve gradient, flow, and opening area, but there was considerable heterogeneity in individual hemodynamic responses. Notably, of the 14 patients in the low-gradient severe group based on echocardiography, nine demonstrated divergent physiological responses consistent with either moderate or high-gradient severe during exercise. All patients - irrespective of stenosis severity - had differential causes of symptoms during exercise with at least one of the following: chronotropic incompetence, abnormal increase in pulmonary artery or left ventricular end-diastolic pressures, or peripheral impairment of oxygen extraction or utilization. These findings demonstrate the safety and feasibility of invasive hemodynamic exercise testing in patients with aortic stenosis and highlight heterogeneity in pressure-flow responses during exercise. Invasive hemodynamic assessment during exercise may help elucidate alternative contributing mechanisms to exertional dyspnea, particularly in patients with aortic stenosis and discordant symptoms and findings.

Left ventricular ejection hemodynamics before and after relief of outflow tract obstruction in patients with hypertrophic obstructive cardiomyopathy and valvular aortic stenosis

Matrix Gla protein (MGP) is a calcification inhibitor and alterations in circulating MGP have been observed in different populations characterized by vascular calcification. We hypothesized that patients with calcific valvular aortic stenosis (AS) would have dysregulated circulating MGP levels. We examined plasma levels of nonphosphorylated carboxylated and undercarboxylated MGP (dp-cMGP and dp-ucMGP, respectively) in 147 patients with symptomatic severe AS and in matched healthy controls. We further investigated the relationship between MGP levels and aortic pressure gradients and valve area by echocardiography and measures of heart failure. Finally, we assessed the prognostic value of elevated plasma dp-ucMGP level in relation to all-cause mortality in patients with AS. We found markedly enhanced plasma levels of dp-cMGP and in particular of dp-ucMGP in patients with symptomatic AS. Although only weak correlations were found with the degree of AS, circulating dp-ucMGP was associated with cardiac function and long-term mortality in multivariate analysis. A dysregulated MGP system may have a role in the development of left ventricular dysfunction in patients with symptomatic AS.

Idiopathic hypertrophic subaortic stenosis (IHSS) is a disease characterized by marked hypertrophy of the left ventricle, involving in particular the interventricular septum and the left ventricula...

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 …

Acquired Stenosis of All Four Heart Valves in a Boxer Mix Dog

The circulatory responses to nitroglycerin and to the Valsalva maneuver were studied in seven patients with idiopathic hypertrophic subaortic stenosis, in five patients with valvular aortic stenosis, and in three patients without obstruction to left ventricular outflow. In contrast to the patients with valvular stenosis who showed no changes or decreases in their aortic valvular pressure gradients, in all the patients with idiopathic hypertrophic subaortic stenosis an increased pressure gradient was observed following nitroglycerin administration. Similar effects on the pressure gradients were observed during the Valsalva maneuver, an augmentation occurring in patients with hypertrophic obstruction, and a fall being noted in patients with valvular stenosis. In one patient with idiopathic hypertrophic subaortic stenosis, the gradients across the right ventricular outflow tract were increased by nitroglycerin and the Valsalva maneuver. It is postulated that this increase in obstruction resulted primarily from a decrease in ventricular size secondary to the reduction in venous return induced by these interventions. It is proposed that reduction in the size of the left ventricle in patients with idiopathic hypertrophic subaortic stenosis, whether induced by changes in venous return, a decrease in arterial pressure, or by agents having a positive inotropic action, reduces the effective size of the outflow orifice. The administration of nitroglycerin and the performance of the Valsalva maneuver in the course of left heart catheterization provide simple methods for detecting the presence of latent obstruction in patients with idiopathic left ventricular hypertrophy and for differentiating idiopathic hypertrophic subaortic stenosis from other forms of obstruction to left ventricular outflow.

AimsEchocardiography and tomographic imaging have documented dynamic changes in aortic stenosis (AS) geometry and severity during both the cardiac cycle and stress-induced increases in cardiac output. However, corresponding pressure gradient vs. flow relationships have not been described.Methods and resultsWe recruited 16 routine transcatheter aortic valve implantations (TAVI’s) for graded dobutamine infusions both before and after implantation; 0.014″ pressure wires in the aorta and left ventricle (LV) continuously measured the transvalvular pressure gradient (ΔP) while a pulmonary artery catheter regularly assessed cardiac output by thermodilution. Before TAVI, ΔP did not display a consistent relationship with transvalvular flow (Q). Neither linear resistor (median R2 0.16) nor quadratic orifice (median R2 < 0.01) models at rest predicted stress observations; the severely stenotic valve behaved like a combination. The unitless ratio of aortic to left ventricular pressures during systolic ejection under stress conditions correlated best with post-TAVI flow improvement. After TAVI, a highly linear relationship (median R2 0.96) indicated a valid valve resistance.ConclusionPressure loss vs. flow curves offer a fundamental fluid dynamic synthesis for describing aortic valve pathophysiology. Severe AS does not consistently behave like an orifice (as suggested by Gorlin) or a resistor, whereas TAVI devices behave like a pure resistor. During peak dobutamine, the ratio of aortic to left ventricular pressures during systolic ejection provides a ‘fractional flow reserve’ of the aortic valve that closely approximates the complex, changing fluid dynamics. Because resting assessment cannot reliably predict stress haemodynamics, ‘valvular fractional flow’ warrants study to explain exertional symptoms in patients with only moderate AS at rest.

This paper presents calculation of the pressure gradient at the point of aortic stenosis in patients with valvular aortic stenosis. The pressure gradients obtained by calculation were compared with the pressure gradients measured using catheterization in 12 patients with valvular aortic stenosis. It has been found that the maximum separation factor influences the maximum blood flow velocity (p<0.05), which was used in calculation of the pressure gradient. There were no statistically significant differences in the pressures obtained by calculation and the pressures obtained by catheterization (p<0.05). These results are in compliance with the widespread use of Doppler echocardiography in practice as a substitute for invasive methods for determining the degree of aortic stenosis. The Doppler echocardiography method is based on calculation presented in this paper.

Evolution of the Continuity Equation in the Doppler Echocardiographic Assessment of the Severity of Valvular Aortic Stenosis

Doppler echocardiographic findings in adults with severe symptomatic valvular aortic stenosis

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 …

BackgroundHaemodynamic exercise testing is important for evaluating patients with dyspnoea on exertion and preserved ejection fraction. Despite very different pathologies, patients with pressure (aortic stenosis (AS)) and volume (mitral regurgitation...

A 59-year-old commercial crawfisherman came to the emergency department complaining of a swollen, red, painful right hand and forearm and subjective fever. The hand was bitten by a snake 4 days earlier when the man was fishing. His only pertinent past history was that 3 years previously he had been sent for an echocardiogram when he saw a physician for fever and fatigue. The patient did not know the results of that test.