Evaluation of low gradient severe aortic stenosis: should we change our outlook in the analysis of clinical data?

Nowadays, technological progress has equipped clinicians with new useful devices for the collection, analysis and presentation of data. As a consequence, many diseases and pathological conditions have been studied in a more detailed way, sometimes with remarkable results. In fact, they are not always validated by the old physiological models. In this respect, we present the case of low gradient severe aortic stenosis, a condition characterised by a small aortic valve area and a low-pressure gradient. According to the mathematical and physical assumptions these readings are contradictory whereas the Doppler-echocardiography shows clearly the existence of such a situation. In this work, we have described the physiological base of this phenomenon and discussed the limitations of the technology used. In this work, we are going to analyse some conditions commonly observed in daily clinical practice in order to prompt a critical outlook in both clinicians and technicians about the instrumentations used and the methods applied.

Automated CO2 angiography: Injection pressure and volume settings.

The purpose of this work was to outline some practical rules for pressure and volume settings in automatic CO2 injection angiographic procedures focusing on the iliac arterial system, since, in current clinical practice, each operator uses his personal experience to obtain imaging results which are not always easy to compare. A theoretical model was thus developed and then verified by a mechanical simulator of the aortoiliac vascular system, with constant and pulsatile blood flow. The conditions of forward and reverse flows have been described, both for constant and pulsatile regimens and pressures, flows, and optical images of the bubbles in glass vessels were simultaneously acquired, analyzed and compared. Our results demonstrated that "good" radiological images (adequate to patient's conditions and clinical need) are strictly related to appropriate settings of gas injection pressure and flow, in accordance with two simple operative rules. These rules prescribe that the patient's pressure, the blood flow in the vessel, and the hydraulic resistance of the gas injection line be known: the first two parameters may be estimated, while the third must be experimentally measured. By following these rules, it is possible to obtain the best results for each clinical setting, a more standardized approach and better imaging during angiographic procedures with carbon dioxide as contrast medium.

Wireless Endocardial Atrial (and Ventricular) Sensing with no Implanted Power Source: a Proposal.

Cardiac electrical activity is mainly evaluated by monitoring the electrical biosignals. This requires a long-lasting power supply to make implantable devices cost-effective and efficient. Since the current trend is to implant catheter-free stand-alone electrodes (implantable cardiac monitors), the need for smaller devices is at odds with the need for long-life batteries. To avoid these problems, we propose a passive endocardial sensor able to monitor the movement of the considered chamber based on a permanent magnet shaped for implantation in the internal chamber of the heart (i.e. the right atrium) and an external gauss meter unit to measure sensor-induced magnetic field variations. Since the magnet is permanent, no replacement is needed after the first implant, thereby reducing the risks linked to invasive procedures, and the battery in the external device can be substituted more easily. To test our idea we used a permanent magnet mounted on the tip of a commercial catheter for heart mapping together with a dedicated gauss meter built in our laboratory. The device was tested in vitro and the magnetic field variations were acquired and measured in different conditions of movement and distances. The results demonstrate the feasibility of our approach and open an interesting new scenario where permanent magnets can be used to monitor the mechanical behaviour of the heart.

How to transform a fixed stroke alternating syringe ventricle into an adjustable elastance ventricle.

Most devices used for bench simulation of the cardiovascular system are based either on a syringe-like alternating pump or an elastic chamber inside a fluid-filled rigid box. In these devices, it is very difficult to control the ventricular elastance and simulate pathologies related to the mechanical mismatch between the ventricle and arterial load (i.e., heart failure). This work presents a possible solution to transforming a syringe-like pump with a fixed ventricle into a ventricle with variable elastance. Our proposal was tested in two steps: (1) fixing the ventricle and the aorta and changing the peripheral resistance (PHR); (2) fixing the aorta and changing the ventricular elastance and the PHR. The signals of interest were acquired to build the ventricular pressure-volume (P-V) loops describing the different physiological conditions, and the end-systolic pressure-volume relationships (ESPVRs) were calculated with linear interpolation. The results obtained show a good physiological behavior of our mock for both steps. (1) Since the ventricle is the same, the systolic pressures increase and the stroke volumes decrease with the PHR: the ESPVR, obtained by interpolating the pressure and volume values at end-systolic phases, is linear. (2) Each ventricle presents ESPVR with different slopes depending on the ventricle elastance with a very good linear behavior. In conclusion, this paper demonstrates that a fixed stroke alternating syringe ventricle can be transformed into an adjustable elastance ventricle.

MR Spectroscopy in Prostate Cancer: New Algorithms to Optimize Metabolite Quantification.

Prostate cancer (PCa) is the most common non-cutaneous cancer in male subjects and the second leading cause of cancer-related death in developed countries. The necessity of a non-invasive technique for the diagnosis of PCa in early stage has grown through years. Proton magnetic resonance spectroscopy (1H-MRS) and proton magnetic resonance spectroscopy imaging (1H-MRSI) are advanced magnetic resonance techniques that can mark the presence of metabolites such as citrate, choline, creatine and polyamines in a selected voxel, or in an array of voxels (in MRSI) inside prostatic tissue. Abundance or lack of these metabolites can discriminate between pathological and healthy tissue. Although the use of magnetic resonance spectroscopy (MRS) is well established in brain and liver with dedicated software for spectral analysis, quantification of metabolites in prostate can be very difficult to achieve, due to poor signal to noise ratio and strong J-coupling of the citrate. The aim of this work is to develop a software prototype for automatic quantification of citrate, choline and creatine in prostate. Its core is an original fitting routine that makes use of a fixed step gradient descent minimization algorithm (FSGD) and MRS simulations developed with the GAMMA libraries in C++. The accurate simulation of the citrate spin systems allows to predict the correct J-modulation under different NMR sequences and under different coupling parameters. The accuracy of the quantifications was tested on measurements performed on a Philips Ingenia 3T scanner using homemade phantoms. Some acquisitions in healthy volunteers have been also carried out to test the software performance in vivo.

Cold pressor test using strain-gauge plethysmography.

This laboratory activity is designed to teach students how to measure forearm muscle blood flow (FBF) to describe the mechanisms of peripheral blood flow thermal regulation in healthy subjects. The cold pressor test (CPT) is the clinical procedure used in the experiment to induce arterial vasoconstriction. Strain-gauge plethysmography is applied on the patient's forearm to noninvasive monitor vasoconstriction effects on local blood perfusion and physiological parameters such as blood pressure (BP) and heart rate (HR). Patients with an altered peripheral vascular resistance (e.g., in hypertension) have different responses to the CPT from healthy subjects. To date, experimental evidence remains unexplained, as we do not know if the BP and HR increase is caused by a decrease in flow rate or an increase in peripheral vascular resistance during the test. To clarify this situation, we have to quantify the parameter we assume is being conditioned by the regulatory physiological intervention, i.e., peripheral vascular resistance. Peripheral vascular resistance quantification can be calculated as the ratio between muscle flow and mean arterial pressure. Students will learn how to apply the instrumental procedure to collect and analyze data before, during, and after the CPT and to describe the physiological responses of the peripheral vascular system to external stressors. They will also learn how to distinguish healthy from pathological responses on the basis of how sympathetic nervous system reactions influence the biomechanics of peripheral vessels.

Automated carbon dioxide digital angiography for lower-limb arterial disease evaluation: safety assessment and comparison with standard iodinated contrast media angiography.

INTRODUCTION: Carbon dioxide (CO2) has been validated as a contrast agent in a large series of studies. A particular advantages of CO2 over iodinated contrast medium (ICM) is the absence of nephrotoxicity and allergic reactions. One of the limitations of CO2 angiography is the difficulty of CO2 manual injection due to its compressibility. The manual gas injection does not permit optimal control of the gas output. Development of an automated CO2 injector has overcome these problems. AIM: This study compares the feasibility, safety, and diagnostic accuracy of automated CO2 digital subtraction angiography (DSA) in comparison with ICM-DSA in the evaluation of critical limb ischemic (CLI) patients. METHODS: We performed DSA with both CO2 and ICM on 40 consecutive CLI patients and directly compared the two techniques. Sixteen females and 24 males participated in the study (mean age, 71.7 years). We assessed the diagnostic accuracy of CO2 in identifying arterial stenosis in the lower limb, with ICM-DSA used as the gold standard. RESULTS: The overall diagnostic accuracy of CO2-DSA was 96.9% (sensitivity, 99.0%; specificity, 96.1%; positive predictive value, 91.1%; negative predictive value, 99.6%). Tolerable minor symptoms occurred in 3 patients. No allergic reactions or significant decline in renal function were observed in patients receiving the CO2 injection. CONCLUSION: Carbon dioxide DSA is a valuable and safe alternative to traditional ICM-DSA for evaluating CLI patients. This modality should be considered as the standard choice for CLI patients undergoing angiographic evaluation who are known to have renal insufficiency or contrast allergy.

Effect of intermediate ZrO2-CaO coatings deposited by cold thermal spraying on the titanium-porcelain bond in dental restorations.

STATEMENT OF PROBLEM: Metal ceramic systems are used for the majority of dental crowns and fixed dental prostheses. However, problems with porcelain bonding are encountered when titanium is used as the substrate. PURPOSE: The purpose of this study was to evaluate the effect of intermediate calcium oxide-stabilized zirconia (ZrO2-CaO) coatings deposited by cold thermal spraying on the titanium-porcelain bonding in dental restorations. MATERIAL AND METHODS: Two different types of ZrO2-CaO coatings obtained by oxyacetylene cold thermal spraying deposition were applied on commercially pure titanium bars before adding the porcelain layer. Type 1 was obtained by directly spraying the ZrO2-CaO powder on the titanium substrate. Type 2 was obtained by spraying a bond coat of nickel-aluminum-molybdenum alloy before spraying the ZrO2-CaO powder. Three-point bend tests according to International Organization of Standardization 9693-1:2012 were carried out to evaluate the debonding strength for the ZrO2-CaO-coated specimens (types 1 and 2) in comparison with a noncoated group (control), which received a traditional bonder-based adhesive technique. The results were compared with ANOVA, followed by the Student-Newman-Keuls test for pairwise comparisons. Scanning electron microscopy and energy dispersion spectroscopy were used to examine the interfacial properties and the failure mode of each group. RESULTS: Mean (±standard deviation) debonding strength values for type 1 coating (25.97 ±2.53 MPa) and control (23.51 ±2.94 MPa) were near the acceptable lower limit of 25 MPa indicated by the International Organization of Standardization 9693-1:2012 and were not significantly different (Student-Newman-Keuls test, P>.05). Type 2 coating produced an improved titanium-porcelain bonding (debonding strength=39.47 ±4.12 MPa), significantly higher than both type 1 (Student-Newman-Keuls test, P<.05) and control (Student-Newman-Keuls test, P<.05). Scanning electron microscopy-energy dispersion spectroscopy analysis confirmed these findings, which revealed a predominant cohesive failure mode for type 2. CONCLUSIONS: An intermediate coating layer of ZrO2-CaO plus a substrate of bonding nickel-aluminum-molybdenum alloy applied by oxyacetylene cold thermal spraying deposition provided an improved titanium-porcelain bond.

Passive aortic counterpulsation: biomechanical rationale and bench validation.

Aortic counterpulsation (IABP) consists in an ECG-controlled forced deflation and inflation of a balloon positioned in the aorta. The device is designed to decrease the ventricular afterload during systole and to increase the coronary driving pressure during diastole. In biomechanical terms, the IABP improves the mechanical matching between the pump and the load, facilitating the transfer of ventricular energy. This paper describes a completely passive aortic counterpulsation solution, with an intra-aortic balloon without a pumping system, designed to improve the mechanical matching between the ventricle and the artery at very low cost and complexity. The only requirement is an external reservoir to amplify the balloon pulsations due to physiologic arterial pressure pulse. Using a cardiovascular simulator and changing the reservoir pressure, a systolic not negligible (7.8ml) gas volume exchange between the intra-aortic balloon and the reservoir was measured. The same cardiovascular simulator was used to demonstrate an increase in stroke volume in three conditions of progressive ventricular failure, by detecting a change in systolic and diastolic arterial pressures and stroke volume (SV). The maximal arterial pressure always decreased and the diastolic pressure increased. The SV increased up to 7.8%, demonstrating an arterial elastance reduction and better ventricular-aortic mechanical matching and energy transfer.

Mechanical aspects of CO2 angiography.

The aim of this paper is to clarify some physical-mechanical aspects involved in the carbon dioxide angiography procedure (CO2 angiography), with a particular attention to a possible damage of the vascular wall. CO2 angiography is widely used on patients with iodine intolerance. The injection of a gaseous element, in most cases manually performed, requires a long training period. Automatic systems allow better control of the injection and the study of the mechanical behaviour of the gas. CO2 injections have been studied by using manual and automatic systems. Pressures, flows and jet shapes have been monitored by using a cardiovascular mock. Photographic images of liquid and gaseous jet have been recorded in different conditions, and the vascular pressure rises during injection have been monitored. The shape of the liquid jet during the catheter washing phase is straight in the catheter direction and there is no jet during gas injection. Gas bubbles are suddenly formed at the catheter's hole and move upwards: buoyancy is the only governing phenomenon and no bubbles fragmentation is detected. The pressure rise in the vessel depends on the injection pressure and volume and in some cases of manual injection it may double the basal vascular pressure values. CO2 angiography is a powerful and safe procedure which diffusion will certainly increase, although some aspects related to gas injection and chamber filling are not jet well known. The use of an automatic system permits better results, shorter training period and limitation of vascular wall damage risk.

Decrease in patient radiation exposure by a tantalum filter during electrophysiological procedures.

AIM: Minimization of X-ray exposure remains a primary issue in cardiac electrophysiology. The effectiveness of X-ray beam filtration during cardiac electrophysiological procedures was therefore studied, using a 0.05-mm-thick tantalum (Ta) foil, as a filter on the primary X-ray beam, to reduce the patient dose without degradation of image quality. METHOD: Preliminary tests were made on a phantom developed with polymethylmethacrylate, catheters, and guide wires. The filter was then used in patients during cardiac procedures. Identical patient images were obtained with and without the Ta filter insertion and the ratio between image quality and patient dose was evaluated. Changes in patient dose and signal-to-noise ratio, as image quality index were measured on the phantom and in patients. RESULTS AND CONCLUSIONS: When the Ta filter was used, the mean effective individual patient dose decreased by 3 to 40% (mean reduction = 27%), with no perceivable difference in image quality estimated by electrophysiologists. This Ta filter may be useful to limit the radiation exposure of patients and operators during cardiac procedures.

Mechanical simulator of the cardiovascular system.

To devise and to build a mechanical simulator of the cardiovascular system of increasing complexity is a fascinating experience for a medical Physicist. We did it, and the effort to match the solutions with the objectives forced us to deepen the knowledge of the physiological aspects, to devise different solutions and to compare their results. This paper describes the final solution and shows the results, discussing the theoretical and practical aspects of the different choices. The ventricle is simulated by a pumping syringe with an external pulsing chamber to accomplish the Frank-Starling mechanism; the coronary circulation by a nonlinear hydraulic resistance device; the aorta by different wall thickness rubber tubes; the arterial vascular resistance by a thin, variable length tube; the venous reservoir by a variable volume chamber connected to a reservoir simulating the atrium. The simulator was mainly devoted to teaching purposes, but the possibility to modify the mechanical characteristics of the single components moved it to be used also for research, with an unexpected satisfaction.

Frequency, determinants, and clinical relevance of acute coronary syndrome-like electrocardiographic findings in patients with acute aortic syndrome.

We investigated frequency/characteristics of acute coronary syndrome-like (ACS-like) electrocardiographic (ECG) profiles among patients with a final diagnosis of acute aortic syndrome (AAS), and explored pathophysiologic determinants and prognostic relevance within each Stanford subtype. We blindly reviewed presentation electrocardiograms of 233 consecutive patients with final diagnosis of AAS (164 Stanford type A) at a regional treatment center. Prevalence of ACS-like ECG findings was 27% (type A, 26%, type B, 29%); most were non-ST-elevation myocardial infarction-like. Patients with ACS-like ECG findings more often had coronary ostia involvement (p=0.002), pleural effusion (p=0.02), significant aortic regurgitation (p=0.01), and troponin positivity (p=0.001). ACS-like ECG profile in type A disease was independently associated with coronary ostia involvement (odds ratio [OR] 5.27, 95% confidence interval [CI] 1.75 to 15.88). ACS-like ECG profile predicted in-hospital mortality (OR 2.90, 95% CI 1.24 to 6.12), as did age (each incremental 10-year: OR 1.59, 95% CI 1.14 to 2.22), and syncope at presentation (OR 2.90, 95% CI 1.16 to 7.24). In conclusion, about 25% of our AAS patients (in either Stanford subtype) presented ACS-like ECG patterns-often with non-ST-elevation myocardial infarction characteristics-which could cause misdiagnosis. ACS-like ECG profile was associated with more complicated disease, and in type A disease was a strong independent predictor of in-hospital mortality.

Measurement of oxygen uptake: validation of a "mask-free" method.

In clinical practice, oxygen uptake is an indicator of cardiopulmonary performance. Most commercial systems measure oxygen uptake by collecting expired air through masks or mouthpieces which are often poorly tolerated by the patient. We have developed and validated a novel mask-free system to improve patient comfort and performance. The prototype is composed of a soft walled funnel that collects and conveys the expired air, together with some external air, in a mixing chamber by means of an aspiration system. Oxygen concentration and airflow are measured and then oxygen uptake is calculated. Direct comparison between calculated and preset oxygen uptake values obtained by a mechanical simulator was performed. Errors ranged between 1% and 3.3%, depending on the absolute value of oxygen consumption. Then the prototype was connected "in-series" with a breath-by-breath commercial system, and ten subjects were submitted to a standard stress test. The results showed good agreement (R=0.94) and a mean difference of 5% between the peak values. The longer response time of the prototype caused a delay between the two .V(O2)(t) curves, leading to an underestimation in the exercise phase and an overestimation in the recovery phase, suggesting more technical improvements. Nevertheless in its present form the new system can be used in the whole exercise phase and, with caution, also in the recovery phase.

A mechanical device for aortic compliance modulation: in vitro simulation of aortic dissection treatment.

Stanford type A aortic dissection often rapidly leads to death from aortic rupture. We considered the possibility of introducing a passive counterpulsating damper into the dissected aorta in order to limit the physical stress associated with ventricular ejection and increase the diastolic aorto-ventricular pressure gradient. We conceived a damping device comprising an intravascular balloon connected to an adjustable external reservoir to regulate the air pressure inside the balloon, and performed a simulation study using a mechanical model of the cardiovascular system, mimicking aortic dissection. When the balloon was completely deflated, the behavior of the aortic pressure signal was typical of low-compliance aortic dissection, as characterized by an augmented maximum systolic value, accentuated diastolic decay, and a very low end-diastolic value. Balloon inflation (at incremental steps to 90 mmHg) progressively restored the aorto-ventricular pressure gradient and reduced peak systolic pressure values, leading to progressive improvements in the characteristics of the aortic pressure curve in terms of reduction in the maximum systolic value and slower diastolic decay. The proposed mechanism might exert beneficial effects at two levels: (1) directly, by reducing mechanical stress on the arterial wall; (2) indirectly, by allowing safer use of pharmaceutical agents (beta-blockers etc.). In vivo animal simulation studies are warranted to verify the effects of the device and optimize balloon shape and volume in a realistic pathophysiological setting.

Endoscopic fetal surgery: in vitro thermic effect of electrosurgical units.

OBJECTIVE: The study focused on the safety of electrosurgical devices in endoscopic fetal surgery. The thermic effects of monopolar electric waves were studied in vitro in order to obtain safety indications in terms of mode of intramniotic application of electrical devices (time and number of shots; volts; and distance from tissues to be preserved). STUDY DESIGN: A glass model filled with saline solution, and an electrical device with resistor and voltage supply, were constructed to reproduce the physical effects of thermic conductivity in vitro; a Swan-Ganz thermic sensor was used to measure the temperature inside the beuta. Different series of tests were carried out. RESULTS: The maximal increase (8.60 +/- 0.04 degrees C) takes place at the external surface of the resistor (distance: 0 cm), while at 2 cm, the temperature of the saline solution does not change. CONCLUSIONS: Our tests demonstrate that in order to avoid any kind of risk during electrosurgical procedures on fetuses, the electrode must be placed at least 0.5 cm from delicate tissues.

Relationship between psychiatric disorders and physical status during the course of a heart transplantation program: a prospective, longitudinal study.

BACKGROUND: Evidence of a lack of relationship between psychiatric disorders and physical status during a heart transplantation (HT) program would configure mental well-being as an independent endpoint deserving specific interventions. METHODS: We report a prospective, longitudinal study on patients (n=127) undergoing HT in order to investigate the relationship between psychiatric disorders and physical status. RESULTS: At pre-HT evaluation, at least one psychiatric disorder according to the DSM-IV diagnoses was present in 27 patients (21%); the prevalence of psychiatric disorders was not related (p > or = 0.150) to physical status (assessed by clinical, electrocardiographic, echocardiographic, and hemodynamic parameters). At post-HT evaluation 1 year after HT, all clinical-instrumental parameters significantly improved (p < or = 0.016), but not the prevalence of psychiatric disorders, which were diagnosed in 34 patients (p = 0.016 vs pre-HT). CONCLUSIONS: During the HT program, no significant relationship exists between physical status and prevalence of psychiatric disorders, which increases after the operation. This finding indicates the need for the mandatory provision of adequate psychological support during all of the phases of the HT experience.

P wave dispersion and short-term vs. late atrial fibrillation recurrences after cardioversion.

BACKGROUND: P wave dispersion has been previously suggested as a potential tool for predicting the risk of recurrence of atrial fibrillation after electrical cardioversion. We investigated whether different P wave dispersion values are associated with recurrence of atrial fibrillation in the short (< or =1 month after cardioversion) and longer term. METHODS: In 37 patients with long-lasting persistent atrial fibrillation (mean duration 21 +/- 36 months) with (n = 19) or without (n = 18) amiodarone pretreatment as antiarrhythmic prophylaxis, maximum and minimum P wave duration and P wave dispersion were measured 1 min after internal cardioversion. RESULTS: P wave dispersion was lower in patients with amiodarone pretreatment (28.3 +/- 9.5 vs. 21.9 +/- 7.3 ms, P = 0.029). The subgroups of patients with recurrence of atrial fibrillation at 1 month or in the long-term did not differ from the rest of the study sample regarding age, sex, atrial fibrillation duration, left atrial dimensions or ejection fraction. P wave dispersion was significantly higher in patients with short-term atrial fibrillation recurrence (< or = 1 month) than in the rest of the population. Furthermore, P wave dispersion values >25 ms were associated with a higher short-term relapse rate. No significant relation was present in the long-term. CONCLUSIONS: Our results suggest that P wave dispersion analysis immediately after internal cardioversion may help predict short-term recurrences of atrial fibrillation. These findings may be related to different mechanisms and predisposing factors for short-term and late recurrences. The long-term predictive value of serial evaluations of P wave dispersion during follow-up deserves investigation.