A ventricular-vascular coupling model in presence of aortic stenosis

In patients with aortic stenosis, the left ventricular afterload is determined by the degree of valvular obstruction and the systemic arterial system. We developed an explicit mathematical model formulated with a limited number of independent parameters that describes the interaction among the left ventricle, an aortic stenosis, and the arterial system. This ventricular-valvular-vascular (V(3)) model consists of the combination of the time-varying elastance model for the left ventricle, the instantaneous transvalvular pressure-flow relationship for the aortic valve, and the three-element windkessel representation of the vascular system. The objective of this study was to validate the V(3) model by using pressure-volume loop data obtained in six patients with severe aortic stenosis before and after aortic valve replacement. There was very good agreement between the estimated and the measured left ventricular and aortic pressure waveforms. The total relative error between estimated and measured pressures was on average (standard deviation) 7.5% (SD 2.3) and the equation of the corresponding regression line was y = 0.99x - 2.36 with a coefficient of determination r(2) = 0.98. There was also very good agreement between estimated and measured stroke volumes (y = 1.03x + 2.2, r(2) = 0.96, SEE = 2.8 ml). Hence, this mathematical V(3) model can be used to describe the hemodynamic interaction among the left ventricle, the aortic valve, and the systemic arterial system.     

心电图左心室劳损和左心室肥厚对主动脉瓣狭窄患者预后的影响

目的:探讨心电图左心室劳损(LV)和左心室肥厚(LVH)对无症状主动脉瓣狭窄患者预后的影响。方法:到我院治疗的主动脉瓣狭窄患者766例,心电图左心室劳损和左心室肥厚的预测值用Sokolow-Lyon(SL)电压标准和Cornell电压-时间(CVDP)标准评估,通过对其他预后协变量调整并进行评价。结果:心电图左心室劳损患者的心肌梗死的累计发生率显著高于非心电图劳损的患者(HR=2.7,95%CI:1.4-5.3,P=0.006)。与非心电图左心室肥厚的患者比较,SL标准与CVDP标准联用诊断的左心室肥厚患者心力衰竭的风险显著增加(95%CI:4.7-26.4,P0.001);行主动脉瓣置换术风险显著增加(95%CI:1.6-3.2,P0.001);非致死性梗死、心力衰竭或心血管死亡的复合终点风险也显著增加(95%CI:1.2-3.7,P0.05)。结论:心电图LV和LVH是无症状主动脉瓣狭窄患者预后不良的独立预测因子。     

Natural history and management of chronic aortic valve disease.

Chronic aortic valve disease involving stenosis, regurgitation or both is insidious and progressive. Severe valvular dysfunction may be present for years without symptoms, but functional deterioration is often rapid once congestive heart failure, angina or syncope with effort is present. As the severity of aortic stenosis may not be easy to assess clinically, the relative usefulness of various tests is considered in this paper. The difficulty with chronic aortic regurgitation lies not in diagnosing the problem but in detecting early left ventricular dysfunction in time to perform the surgery that can prevent further functional deterioration. Patients with significant aortic valve disease should undergo surgery when the important symptoms of dyspnea, angina or syncope with effort first appear. Surgery should also be considered in selected patients with aortic regurgitation in whom left ventricular function has diminished even without symptoms.     

Hemodynamic effects of pacing-induced tachycardia in valvular aortic stenosis.

The hemodynamic effects of tachycardia were studied in 13 patients with valvular aortic stenosis. Observations were made during sinus rhythm (average heart rate 80 beats/min) and two periods (P1 and P2) when atrial pacing increased the heart rate to 109 and 131 beats/min respectively. The cardiac index did not change, but the left ventricular stroke work index fell from 61.8 to 39.5 g X m/m2 (p less than 0.001) as the heart rate increased. The left ventricular end-diastolic pressure averaged 18 mm Hg during sinus rhythm and fell to about 11.5 mm Hg at P1 and P2 (p less than 0.001). The brachial arterial systolic pressure did not change during pacing, but the left ventricular systolic pressure fell from 208 mm Hg to 201 mm Hg during P1 (p less than 0.05) and 193 mm Hg during P2 (p less than 0.001). The mean systolic aortic valve gradient averaged 64 mm Hg during sinus rhythm and fell to 51 mm Hg during P2 (p less than 0.001), and the peak aortic valve gradient fell from 82 to 69 mm Hg during P2 (p less than 0.001). The left ventricular ejection time fraction increased from 26.9% during sinus rhythm to 31.9% during P1 (p less than 0.05) and 34.7% during P2 (p less than 0.005). Because of the prolonged left ventricular ejection time fraction and smaller stroke volume, a smaller pressure gradient developed across the stenosed valve at higher heart rates. The pacing test was of little value in assessing left ventricular function and thus is not useful during invasive investigations of valvular aortic stenosis.     

Permanent Ligation of the Left Anterior Descending Coronary Artery in Mice: A Model of Post-myocardial Infarction Remodelling and Heart Failure

Heart failure is a syndrome in which the heart fails to pump blood at a rate commensurate with cellular oxygen requirements at rest or during stress. It is characterized by fluid retention, shortness of breath, and fatigue, in particular on exertion. Heart failure is a growing public health problem, the leading cause of hospitalization, and a major cause of mortality. Ischemic heart disease is the main cause of heart failure.Ventricular remodelling refers to changes in structure, size, and shape of the left ventricle. This architectural remodelling of the left ventricle is induced by injury (e.g., myocardial infarction), by pressure overload (e.g., systemic arterial hypertension or aortic stenosis), or by volume overload. Since ventricular remodelling affects wall stress, it has a profound impact on cardiac function and on the development of heart failure. A model of permanent ligation of the left anterior descending coronary artery in mice is used to investigate ventricular remodelling and cardiac function post-myocardial infarction. This model is fundamentally different in terms of objectives and pathophysiological relevance compared to the model of transient ligation of the left anterior descending coronary artery. In this latter model of ischemia/reperfusion injury, the initial extent of the infarct may be modulated by factors that affect myocardial salvage following reperfusion. In contrast, the infarct area at 24 hr after permanent ligation of the left anterior descending coronary artery is fixed. Cardiac function in this model will be affected by 1) the process of infarct expansion, infarct healing, and scar formation; and 2) the concomitant development of left ventricular dilatation, cardiac hypertrophy, and ventricular remodelling.Besides the model of permanent ligation of the left anterior descending coronary artery, the technique of invasive hemodynamic measurements in mice is presented in detail.     

Hypertrophy of the heart; electrocardiographic distinction between physiologic and pathologic enlargement

Electrocardiograms of marathon runners were examined to study hypertrophy of the heart due to prolonged physical exertion and to differentiate this from hypertrophy due to various disease states, especially essential hypertension, aortic valvular disease and coarctation of the aorta. The electrocardiogram of the marathon runners was characterized by a slow cardiac rate, high voltage of the QRS complexes and T waves in the standard and/or precordial leads with normal R/T ratios. There was moderate enlargement of the heart as observed on teleoroentgenogram. These findings are characteristic of physiologic hypertrophy of the heart and should be suspected among patients having a history of athletics calling for endurance. Immediately after running, all waves showed an increased voltage and the heart size decreased. The concept of the secondary T wave in hypertension as a part of the left ventricular strain pattern was challenged by the observation that the increased voltage of the R waves in lead V5 and other leads seen in marathon runners and in certain patients with hypertension, aortic stenosis, aortic insufficiency and coarctation of the aorta were not necessarily associated with typical discordant S-T segments and T waves. There was a higher incidence of dyspnea, angina pectoris and cardiac enlargement among hypertensive patients with discordant T waves than among hypertensive patients without these changes. Thus it is felt that the discordant waves are primary and are not merely secondary to the increased area of the R waves. Primary T waves suggest myocardial disease, possibly anoxia of the subendocardium.     

HYPERTROPHY OF THE HEART—Electrocardiographic Distinction Between Physiologic and Pathologic Enlargement

Electrocardiograms of marathon runners were examined to study hypertrophy of the heart due to prolonged physical exertion and to differentiate this from hypertrophy due to various disease states, especially essential hypertension, aortic valvular disease and coarctation of the aorta. The electrocardiogram of the marathon runners was characterized by a slow cardiac rate, high voltage of the QRS complexes and T waves in the standard and/or precordial leads with normal R/T ratios. There was moderate enlargement of the heart as observed on teleoroentgenogram. These findings are characteristic of physiologic hypertrophy of the heart and should be suspected among patients having a history of athletics calling for endurance. Immediately after running, all waves showed an increased voltage and the heart size decreased. The concept of the secondary T wave in hypertension as a part of the left ventricular strain pattern was challenged by the observation that the increased voltage of the R waves in lead V5 and other leads seen in marathon runners and in certain patients with hypertension, aortic stenosis, aortic insufficiency and coarctation of the aorta were not necessarily associated with typical discordant S-T segments and T waves. There was a higher incidence of dyspnea, angina pectoris and cardiac enlargement among hypertensive patients with discordant T waves than among hypertensive patients without these changes. Thus it is felt that the discordant waves are primary and are not merely secondary to the increased area of the R waves. Primary T waves suggest myocardial disease, possibly anoxia of the subendocardium.     

Left ventricular hypertrophy in obese hypertensives: is it really eccentric? (An echocardiographic study)

In order to study left ventricular hypertrophy patterns in obese hypertensives, we examined 132 patients with essential hypertension by 2D, M-mode and Doppler echocardiography. The patients were classified in four comparable groups, corresponding to the values of Quetelet's body mass index (BMI) and grades of obesity. More obese hypertensives had on average larger left ventricles with thicker walls and larger left atria than less obese, or lean ones. Left ventricular mass increased significantly and progressively with advancing grades of obesity, but relative wall thickness (wall thickness/cavity size ratio) did not diminish. Doppler echocardiography revealed significantly higher prevalence of left ventricular diastolic dysfunction among obese than among lean hypertensives. In the second part of our study, we analyzed the subgroups defined by the severity of hypertension and the age of the patients. The correlation of the indices of left ventricular and left atrial hypertrophy with the BMI values was considerably better in the group of moderate than in the group of mild hypertension. The r values were 0.62 vs. 0.22 for left ventricular mass and 0.64 vs. 0.26 for left atrial dimension. The group of patients with severe hypertension was characterized by left ventricular cavity enlargement in correlation with increasing BMI values, but without corresponding left ventricular wall thickening. So called left ventricular "eccentricity index", as the reverse value of relative wall thickness, correlated well (r = 0.76) with the BMI values. The indices of left ventricular hypertrophy correlated with the BMI values slightly better in middle age groups than in the groups of the youngest (< or = 30 years) or the eldest (> or = 61 years) hypertensives. In conclusion, eccentric left ventricular hypertrophy does not seem to be a distinctive feature of hypertensive heart disease in obesity. There is only some tendency toward the "eccentricity" of left ventricular geometry which becomes more apparent in more severe forms of hypertension, especially in very obese persons.     

Congenital Aortic Stenosis: Some Observations on the Natural History and Clinical Assessment

Three hundred patients, 30 years of age or under, with the clinical diagnosis of aortic stenosis were reviewed to provide information on the accuracy of clinical assessment and the natural history of the condition when left untreated. Sudden death was uncommon and occurred only in patients with clinical evidence of severe obstruction. In infants, the early presentation and lethal nature of aortic stenosis appeared to result from the presence of additional cardiac lesions. Correlation of clinical assessment with hemodynamic data in 83 patients indicated that important stenosis was present if the systolic murmur was accompanied by a thrill and associated with an increased left ventricular impulse, decreased brachial artery pulse pressure, or left ventricular hypertrophy on the electrocardiogram. The site of obstruction could not be established with certainty by clinical examination, but an early systolic ejection click was strong evidence against subvalvular stenosis.     

Prevention of concentric hypertrophy and diastolic impairment in aortic-banded rats treated with resveratrol

This study was designed to examine the effects of the antioxidant resveratrol on cardiac structure and function in pressure overload (PO)-induced cardiac hypertrophy. Male Sprague-Dawley rats were subjected to sham operation and the aortic banding procedure. A subgroup of sham control and aortic-banded rats were treated with resveratrol for 2 wk after surgery. Echocardiographic analysis of cardiac structure and function along with Western blot analysis of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and redox factor-1 (ref-1) were performed in all groups after 4 wk of surgery. Banded rats showed significantly increased left ventricle-to-body weight ratio. Echocardiographic analysis showed that the interventricular septal wall thickness and left ventricular posterior wall thickness at systole and diastole were significantly increased in banded rats. Also, a significant increase in isovolumic relaxation time was observed in banded rats. Measured eNOS, iNOS, and ref-1 protein levels were significantly reduced in banded rats. Resveratrol treatment prevented the above changes in cardiac structure, function, and protein expression in banded rats. Aortic banding after 4 wk resulted in concentric remodeling and impaired contractile function due to PO on the heart. The 2-wk treatment with resveratrol was found to abolish PO-induced cardiac hypertrophy. Resveratrol may therefore be beneficial against PO-induced cardiac hypertrophy found in clinical settings of hypertension and aortic valve stenosis.     

Estimation of valvular resistance of segmented aortic valves using computational fluid dynamics

Aortic valve stenosis is associated with an elevated left ventricular pressure and transaortic pressure drop. Clinicians routinely use Doppler ultrasound to quantify aortic valve stenosis severity by estimating this pressure drop from blood velocity. However, this method approximates the peak pressure drop, and is unable to quantify the partial pressure recovery distal to the valve. As pressure drops are flow dependent, it remains difficult to assess the true significance of a stenosis for low-flow low-gradient patients. Recent advances in segmentation techniques enable patient-specific Computational Fluid Dynamics (CFD) simulations of flow through the aortic valve. In this work a simulation framework is presented and used to analyze data of 18 patients. The ventricle and valve are reconstructed from 4D Computed Tomography imaging data. Ventricular motion is extracted from the medical images and used to model ventricular contraction and corresponding blood flow through the valve. Simplifications of the framework are assessed by introducing two simplified CFD models: a truncated time-dependent and a steady-state model. Model simplifications are justified for cases where the simulated pressure drop is above 10 mmHg. Furthermore, we propose a valve resistance index to quantify stenosis severity from simulation results. This index is compared to established metrics for clinical decision making, i.e. blood velocity and valve area. It is found that velocity measurements alone do not adequately reflect stenosis severity. This work demonstrates that combining 4D imaging data and CFD has the potential to provide a physiologically relevant diagnostic metric to quantify aortic valve stenosis severity.     

Undiagnosed hypertrophic obstructive cardiomyopathy during transcatheter aortic valve replacement: a case report

Background

Transcatheter aortic valve replacement is indicated for severe symptomatic aortic stenosis in patients who have a very high or prohibitive surgical risk as assessed pre-procedurally by the Society of Thoracic Surgery Risk Score, EuroSCORE (II), frailty testing, and other predictors. When combined with another left ventricular outflow tract obstruction, careful consideration must be taken prior to proceeding with transcatheter aortic valve replacement because an additional masked left ventricular outflow tract pathology can lead to challenging hemodynamics in the peri-deployment phase, as reported in this case.

Case presentation

A 56-year-old Caucasian man with multiple comorbidities and severe aortic stenosis underwent transcatheter aortic valve replacement under monitored anesthesia care. During the deployment phase, he developed dyspnea that progressed to pulmonary edema requiring emergent conversion to general anesthesia, orotracheal intubation, acute respiratory distress syndrome-type ventilation, and vasopressor medications. Intraoperative transesophageal echocardiography was performed and hypertrophic obstructive cardiomyopathy with systolic anterior motion of the mitral valve was discovered as an underlying pathology, undetected on preoperative imaging. After treatment with beta blockers, fluid resuscitation, and alpha-1 agonists, he stabilized and was eventually discharged from our hospital without any lasting sequelae.

Conclusions

Patients with aortic stenosis most often develop symmetric hypertrophy; however, a small subset has asymmetric septal hypertrophy leading to left ventricular outflow tract obstruction. In cases of severe aortic stenosis, however, evidence of left ventricular outflow tract obstruction via both symptoms and echocardiographic findings may be minimized due to extremely high afterload on the left ventricle. Diagnosing a left ventricular outflow tract obstruction as the cause of hemodynamic instability during transcatheter aortic valve replacement, in the absence of abnormal findings on echocardiogram preoperatively, requires a high index of clinical suspicion. The management of acute onset left ventricular outflow tract obstruction intraoperatively consists primarily of medical therapy, including rate control, adequate volume resuscitation, and avoidance of inotropes. With persistently elevated gradients, interventional treatments may be considered.

     

Aortic valve stenosis: persistence of infective agents or noninfective inflammatory process?]

The probable risk factors leading to aortic valve calcification are not clearly defined. The cross-sectional study of 85 patients with vascular and valvular calcification was performed. Correlations between the immune tests and aortic stenosis severity were investigated. The predictors of aortic valve calcification were probably C-reactive protein and interleukin-6. The predictors of aortic stenosis progression were interleukin-8, antibodies of Chlamydia pneumoniae and cytomegalovirus, and dysregulation of complement's components. Implication of immune reactivity could influence aortic valve calcification.     

Contributions of hemodynamic monitoring to the treatment of chronic congestive heart failure.

Optimal therapy for congestive cardiac failure requires identification of correctable factors that aggravate it as well as an understanding of its etiology. Increased sympathetic nervous system activity, reduced renal blood flow, and cardiac hypertrophy and dilation are the main compensatory processes that occur in response to cardiac failure. Although they may be of initial benefit in supporting a reduced stroke volume, they may ultimately prove self-defeating. New drugs for the treatment of severe congestive heart failure include dopamine, which has a selective nonadrenergic dilator effect on the renal vascular bed, and dobutamine, which has potent inotropic effects, lowers the left ventricular filling pressure and does not increase the heart rate or the systemic vascular resistance. By reducing both the resistance to left ventricular ejection and the venous return to the right heart, vasodilators result in improved peripheral perfusion and reduced pulmonary congestion. Optimal therapy for refractory cardiac failure can be rationally determined by characterizing the hemodynamic profile through measurement of the mean arterial pressure, the left ventricular filling pressure, the cardiac output and the systemic vascular resistance. The specific therapy can then be effectively and safely delivered by a careful analysis of the dose-response relation as identified by hemodynamic monitoring.     

Estimation of aortic distensibility and instantaneous left ventricular volume in living man

A method is presented in this paper for the estimation of aortic distensibility and instantaneous systolic left ventricular volume in living man in the absence of valvular regurgitation. The method is based on a simple, elastic-reservoir-theory, model of the circulatory system and requires no assumption concerning the geometry of the left ventricle. The input data required for this mathematical model consists of stroke volume, an aortic pressure record over an entire cardiac cycle and end diastolic ventricular volume. The procedure developed here for the estimation of aortic distensibility and instantaneous left ventricular volume is very practical from a computational point of view. It is believed that it will yield useful information concerning two clinically important quantities which cannot be measured directly in living man and will facilitate the study of correlations between these quantities and various physiological and pathological states. Results are presented in the paper for six cardiac patients. The requisite data in each case was obtained in the Cardiac Research Laboratory at the Peter Bent Brigham Hospital.     

缬沙坦联合氨氯地平治疗高血压伴左心肥厚的疗效及对心功能的影响

目的:通过探讨缬沙坦联合氨氯地平治疗高血压伴左心肥厚患者的疗效及对心功能的影响,为临床治疗提供依据。方法:选择2010年1月~2014年12月我院收治的高血压伴左心室肥厚患者共120例,按照随机数字表法随机分为观察组和对照组。对照组患者给予氨氯地平,观察组患者缬沙坦联合氨氯地平治疗,治疗6个月后,观察两组患者舒张压(DBP)、收缩压(SBP)、心率(HR)、室间隔厚度(IVST),左室后壁厚度(LVPWT)、左室舒张末期内径(LVDd)和左室重量指数(LVMI)。结果:治疗后,两组患者SBP、DBP和HR均较治疗前显著降低,差异有统计学意义(P0.05);观察组患者SBP、DBP和HR均低于对照组,差异有统计学意义(P0.05)。治疗后,两组患者IVST、IVPWT、LVDd和LVMI均较治疗前显著降低,差异有统计学意义(P0.05);观察组患者IVST、IVPWT、LVDd和LVMI均低于对照组,差异有统计学意义(P0.05)。结论:缬沙坦联合氨氯地平治疗高血压伴左心肥厚患者,能够降低患者血压、逆转左心室肥厚,改善患者心功能,疗效优于氨氯地平单独治疗,值得临床推广应用。     

Effects of enhanced ventricular filling on cardiac pump performance in exercising dogs

The extent to which the normal increase in stroke volume during exercise can be augmented by increasing preload by dextran infusion was studied in seven dogs. Each dog ran 3 min on a level treadmill at mild (3-4 mph), moderate (6-8 mph), and severe (9-13 mph) loads during the control study and immediately after 10% dextran 14 ml/kg iv. During severe exercise dextran-augmented stroke volume (+5.4 ml or 19% vs. exercise without dextran, P less than 0.01) and left ventricular end-diastolic diameter and pressure did not change heart rate, aortic pressure, or maximum derivative of left ventricular pressure but decreased systemic vascular resistance by 16%. Similar increases in stroke volume and preload after dextran occurred during mild and moderate exercise when arterial pressure and heart rate were unchanged or increased and systemic vascular resistance was decreased. Thus altering preload above those levels normally encountered during exercise is a potential mechanism to increase stroke volume and cardiac output.     

Left heart catheterization; the clinical importance of findings

Left heart catheterization using the transbronchial route to obtain pressures in the left atrium and left ventricle was used successfully in 29 cases with no mortality or morbidity. It was found to be useful in differentiating between mitral stenosis and mitral insufficiency, as well as determining the amount of aortic stenosis present when there was involvement of the aortic valve. The technique was also helpful in determining which is the predominant lesion when there is a disease of the aortic and mitral valves. In two patients in a series of 29, data obtained by left heart catheterization forestalled operation on the basis of a mistaken diagnosis of mitral stenosis when actually no mitral valvular disease was present. In another eight patients, the predominant lesion was found to be mitral stenosis rather than mitral insufficiency as it was thought to be before catheterization. In two patients, who had only systolic murmurs, catheterization revealed mitral stenosis rather than mitral insufficiency. In four patients who were thought to have mixed valvular disease, left heart catheterization showed only aortic valvular disease.     

LEFT HEART CATHETERIZATION—The Clinical Importance of Findings

Left heart catheterization using the transbronchial route to obtain pressures in the left atrium and left ventricle was used successfully in 29 cases with no mortality or morbidity. It was found to be useful in differentiating between mitral stenosis and mitral insufficiency, as well as determining the amount of aortic stenosis present when there was involvement of the aortic valve. The technique was also helpful in determining which is the predominant lesion when there is a disease of the aortic and mitral valves.In two patients in a series of 29, data obtained by left heart catheterization forestalled operation on the basis of a mistaken diagnosis of mitral stenosis when actually no mitral valvular disease was present. In another eight patients, the predominant lesion was found to be mitral stenosis rather than mitral insufficiency as it was thought to be before catheterization. In two patients, who had only systolic murmurs, catheterization revealed mitral stenosis rather than mitral insufficiency. In four patients who were thought to have mixed valvular disease, left heart catheterization showed only aortic valvular disease.     

Effect of hyperbaric oxygenation on several functional and morphologic properties of the heart and catecholamine metabolism in the presence of compensatory myocardial hypertrophy]

Rabbits subjected to hyperbaric oxygenation (HBO) for one month following ascending aorta stenosis developed less distinct hypertrophy and signs of myocardial dystrophy with a more distinct enhancement of the left ventricular contractility than animals with aortic stenosis kept under normal pressure. In rabbits with heart hypertrophy developing under HBO the increasing adaptive capacity of the myocardium was accompanied by an elevation in functional reserve of the sympathetic regulation apparatus. Apparently HBO aided the development of the optimum cardiac adaptation to a high afterload.