WEB downloadable software for training in cardiovascular hemodynamics in the (3-D) stress echo lab

When a physiological (exercise) stress echo is scheduled, interest focuses on wall motion segmental contraction abnormalities to diagnose ischemic response to stress, and on left ventricular ejection fraction to assess contractile reserve. Echocardiographic evaluation of volumes (plus standard assessment of heart rate and blood pressure) is ideally suited for the quantitative and accurate calculation of a set of parameters allowing a complete characterization of cardiovascular hemodynamics (including cardiac output and systemic vascular resistance), left ventricular elastance (mirroring left ventricular contractility, theoretically independent of preload and afterload changes heavily affecting the ejection fraction), arterial elastance, ventricular arterial coupling (a central determinant of net cardiovascular performance in normal and pathological conditions), and diastolic function (through the diastolic mean filling rate). All these parameters were previously inaccessible, inaccurate or labor-intensive and now become, at least in principle, available in the stress echocardiography laboratory since all of them need an accurate estimation of left ventricular volumes and stroke volume, easily derived from 3 D echo

Arterial pressure changes monitoring with a new precordial noninvasive sensor

<p>Abstract</p> <p>Background</p> <p>Recently, a cutaneous force-frequency relation recording system based on first heart sound amplitude vibrations has been validated. A further application is the assessment of Second Heart Sound (S2) amplitude variations at increasing heart rates. The aim of this study was to assess the relationship between second heart sound amplitude variations at increasing heart rates and hemodynamic changes.</p> <p>Methods</p> <p>The transcutaneous force sensor was positioned in the precordial region in 146 consecutive patients referred for exercise (n = 99), dipyridamole (n = 41), or pacing stress (n = 6). The curve of S2 peak amplitude variation as a function of heart rate was computed as the increment with respect to the resting value.</p> <p>Results</p> <p>A consistent S2 signal was obtained in all patients. Baseline S2 was 7.2 ± 3.3 m<it>g</it>, increasing to 12.7 ± 7.7 m<it>g </it>at peak stress. S2 percentage increase was + 133 ± 104% in the 99 exercise, + 2 ± 22% in the 41 dipyridamole, and + 31 ± 27% in the 6 pacing patients (p < 0.05). Significant determinants of S2 amplitude were blood pressure, heart rate, and cardiac index with best correlation (R = .57) for mean pressure.</p> <p>Conclusion</p> <p>S2 recording quantitatively documents systemic pressure changes.</p

From Inverse Problems in Mathematical Physiology to Quantitative Differential Diagnoses

The improved capacity to acquire quantitative data in a clinical setting has generally failed to improve outcomes in acutely ill patients, suggesting a need for advances in computer-supported data interpretation and decision making. In particular, the application of mathematical models of experimentally elucidated physiological mechanisms could augment the interpretation of quantitative, patient-specific information and help to better target therapy. Yet, such models are typically complex and nonlinear, a reality that often precludes the identification of unique parameters and states of the model that best represent available data. Hypothesizing that this non-uniqueness can convey useful information, we implemented a simplified simulation of a common differential diagnostic process (hypotension in an acute care setting), using a combination of a mathematical model of the cardiovascular system, a stochastic measurement model, and Bayesian inference techniques to quantify parameter and state uncertainty. The output of this procedure is a probability density function on the space of model parameters and initial conditions for a particular patient, based on prior population information together with patient-specific clinical observations. We show that multimodal posterior probability density functions arise naturally, even when unimodal and uninformative priors are used. The peaks of these densities correspond to clinically relevant differential diagnoses and can, in the simplified simulation setting, be constrained to a single diagnosis by assimilating additional observations from dynamical interventions (e.g., fluid challenge). We conclude that the ill-posedness of the inverse problem in quantitative physiology is not merely a technical obstacle, but rather reflects clinical reality and, when addressed adequately in the solution process, provides a novel link between mathematically described physiological knowledge and the clinical concept of differential diagnoses. We outline possible steps toward translating this computational approach to the bedside, to supplement today's evidence-based medicine with a quantitatively founded model-based medicine that integrates mechanistic knowledge with patient-specific information

Atrial remodelling in hypertensive heart disease: role of Na+ homeostasis and contractility

Arterial hypertension causes hypertensive heart disease. Constant mechanical stress and activation of neurohormonal systems cause structural and functional changes in the myocardium termed “remodelling”. Remodelling is beneficial in the beginning of the disease development; however, with time it becomes detrimental and impairs cardiac function. Remodelling of the myocardium occurs in hypertension, atrial fibrillation and heart failure. These cardiac diseases are tightly linked by the mechanisms of pathological remodelling and induce development and maintenance of one another. Ventricular remodelling has been studied intensively in hypertensive heart disease, however, atrial remodelling has been studied much less and is only poorly understood. Physiology of cardiac myocytes relies on balanced intracellular Na+ homeostasis. Na+ is involved in many cellular processes, such as action potential initiation, Ca2+ homeostasis, intracellular pH, metabolism and contractility. In the first part of the thesis I investigated ionic (Na+ homeostasis) and functional (contractility) atrial remodelling in an animal model of hypertensive heart disease – spontaneously hypertensive rats (SHR). In early hypertension, SHR exhibited elevated blood pressure and isolated left ventricular hypertrophy. The atria were not hypertrophied. Contractility of atrial myocytes and intracellular Na+ concentration ([Na+]i) were both unaltered. Expression of most Na+-handling proteins was unaffected in the atria of SHR. In advanced hypertension, SHR exhibited further progression of left ventricular hypertrophy and signs of heart failure. Left atria were hypertrophied. The contractility of atrial myocytes was reduced. [Na+]i was significantly decreased together with increased expression of the α 1 subunit of Na+/K+-ATPase. Expression of Na+/H+-exchanger was increased, suggesting activation of pro-hypertrophic pathways. Comparison of SHR with and without signs of heart failure (i.e. increased lung weight) revealed development of right ventricular hypertrophy and progression of bi-atrial hypertrophy in SHR with heart failure. Moreover, the impairment of atrial myocyte contractility progressed. However, [Na+]i and the expression of major Na+-handling proteins were not changed during the transition to heart failure. In addition to studies on atrial myocytes, we performed measurements of [Na+]i and contractility of ventricular myocytes from old SHR. In contrast to our findings in the atria, no impairment of contractility or changes in [Na+]i were observed in the ventricular myocytes, indicating atria-specific remodelling. Taken together, the presented results indicate that in early hypertension no significant signs of atrial remodelling in terms of contractility and Na+ homeostasis were found. However, in advanced hypertensive heart disease there was atria-specific functional atrial remodelling, which might contribute to the transition from compensated left ventricular hypertrophy to heart failure. Atrial ionic remodelling is an important factor in the development and maintenance of atrial fibrillation. The role of intracellular Na+ homeostasis in these processes is not understood. In the second part of the thesis, I investigated expression of Na+-handling proteins in right atrial tissue of patients suffering from paroxysmal and chronic atrial fibrillation compared to patients with sinus rhythm. The results indicated that the expression of Na+-handling proteins, including Na+ channels, Na+/H+ exchanger, alpha subunits of Na+/K+-ATPase, phospholemman, was not altered in either paroxysmal or chronic atrial fibrillation. The expression of β 1 subunit of Na+/K+-ATPase was significantly reduced in chronic atrial fibrillation. However, the functional consequences of this change require further investigation. Endothelin-1 plays an important role in the regulation of blood pressure and cardiac physiology. Enhancement of endothelin-1 system activity contributes to cardiac maladaptive remodelling, including disturbances in Ca2+ and Na+ homeostasis in cardiac myocytes. At the age of 7 months, SHR exhibit enhanced endothelin-1 signalling and altered Ca2+ handling. Therefore, in the third part of the thesis we investigated the effect of endothelin-1 receptor blockage on blood pressure and expression and phosphorylation of Ca2+-handling proteins, as well as the expression of proteins involved in endothelin-1 signalling in the atria of SHR. The results revealed that the blockage of endothelin receptors by 8 weeks treatment with macitentan (novel dual endothelin A and endothelin B receptor antagonist) did not lower blood pressure in SHR. Expression and phosphorylation of major Ca2+-handling proteins and endothelin-1 signalling proteins were both unaffected. Thus, the blockage of endothelin receptors did not cause any major changes in atrial Ca2+ remodelling in SH