Longterm peripheral baroreflex and chemoreflex function after bilateral eversion carotid endarterectomy

Introduction The “eversion” technique for carotid endarterectomy (e-CEA), that involves the transection of the internal carotid artery at the carotid bulb and its eversion over the atherosclerotic plaque, has been associated with an increased risk of postoperative hypertension possibly due to a direct iatrogenic damage to the carotid sinus fibers. The aim of this study is to assess the long-term effect of the e-CEA on arterial baroreflex and peripheral chemoreflex function in humans. Methods A retrospective review was conducted on a prospectively compiled computerized database of 3128 CEAs performed on 2617 patients at our Center between January 2001 and March 2006. During this period, a total of 292 patients who had bilateral carotid stenosis ≥70% at the time of the first admission underwent staged bilateral CEAs. Of these, 93 patients had staged bilateral e-CEAs, 126 staged bilateral s- CEAs and 73 had different procedures on each carotid. CEAs were performed with either the eversion or the standard technique with routine Dacron patching in all cases. The study inclusion criteria were bilateral CEA with the same technique on both sides and an uneventful postoperative course after both procedures. We decided to enroll patients submitted to bilateral e-CEA to eliminate the background noise from contralateral carotid sinus fibers. Exclusion criteria were: age >70 years, diabetes mellitus, chronic pulmonary disease, symptomatic ischemic cardiac disease or medical therapy with b-blockers, cardiac arrhythmia, permanent neurologic deficits or an abnormal preoperative cerebral CT scan, carotid restenosis and previous neck or chest surgery or irradiation. Young and aged-matched healthy subjects were also recruited as controls. Patients were assessed by the 4 standard cardiovascular reflex tests, including Lying-to-standing, Orthostatic hypotension, Deep breathing, and Valsalva Maneuver. Indirect autonomic parameters were assessed with a non-invasive approach based on spectral analysis of EKG RR interval, systolic arterial pressure, and respiration variability, performed with an ad hoc software. From the analysis of these parameters the software provides the estimates of spontaneous baroreflex sensitivity (BRS). The ventilatory response to hypoxia was assessed in patients and controls by means of classic rebreathing tests. Results A total of 29 patients (16 males, age 62.4±8.0 years) were enrolled. Overall, 13 patients had undergone bilateral e-CEA (44.8%) and 16 bilateral s-CEA (55.2%) with a mean interval between the procedures of 62±56 days. No patient showed signs or symptoms of autonomic dysfunction, including labile hypertension, tachycardia, palpitations, headache, inappropriate diaphoresis, pallor or flushing. The results of standard cardiovascular autonomic tests showed no evidence of autonomic dysfunction in any of the enrolled patients. At spectral analysis, a residual baroreflex performance was shown in both patient groups, though reduced, as expected, compared to young controls. Notably, baroreflex function was better maintained in e-CEA, compared to standard CEA. (BRS at rest: young controls 19.93 ± 2.45 msec/mmHg; age-matched controls 7.75 ± 1.24; e-CEA 13.85 ± 5.14; s-CEA 4.93 ± 1.15; ANOVA P=0.001; BRS at stand: young controls 7.83 ± 0.66; age-matched controls 3.71 ± 0.35; e-CEA 7.04 ± 1.99; s-CEA 3.57 ± 1.20; ANOVA P=0.001). In all subjects ventilation (VÝ E) and oximetry data fitted a linear regression model with r values > 0.8. Oneway analysis of variance showed a significantly higher slope both for ΔVE/ΔSaO2 in controls compared with both patient groups which were not different from each other (-1.37 ± 0.33 compared with -0.33±0.08 and -0.29 ±0.13 l/min/%SaO2, p<0.05, Fig.). Similar results were observed for and ΔVE/ΔPetO2 (-0.20 ± 0.1 versus -0.01 ± 0.0 and -0.07 ± 0.02 l/min/mmHg, p<0.05). A regression model using treatment, age, baseline FiCO2 and minimum SaO2 achieved showed only treatment as a significant factor in explaining the variance in minute ventilation (R2= 25%). Conclusions Overall, we demonstrated that bilateral e-CEA does not imply a carotid sinus denervation. As a result of some expected degree of iatrogenic damage, such performance was lower than that of controls. Interestingly though, baroreflex performance appeared better maintained in e-CEA than in s-CEA. This may be related to the changes in the elastic properties of the carotid sinus vascular wall, as the patch is more rigid than the endarterectomized carotid wall that remains in the e-CEA. These data confirmed the safety of CEA irrespective of the surgical technique and have relevant clinical implication in the assessment of the frequent hemodynamic disturbances associated with carotid angioplasty stenting.

Evaluation of cardiovascular disease markers in patients submitted to carotid artery stenting or endarterectomy

Introduction. Microembolization during the carotid artery revascularization procedure may cause cerebral lesions. Elevated C-Reactive Protein (hsCRP), Vascular endothelial growth factor (VEGF) and serum amyloid A protein (SAA) exert inflammatory activities thus promoting carotid plaque instability. Neuron specific enolase (NSE) is considered a marker of cerebral injury. Neoangiogenesis represents a crucial step in atherosclerosis, since neovessels density correlates with plaque destabilization. However their clinical significance on the outcome of revascularization is unknown. This study aims to establish the correlation between palque vulnerabilty, embolization and histological or serological markers of inflammation and neoangiogenesis. Methods. Serum hsCRP, SAA, VEGF, NSE mRNA, PAPP-A mRNA levels were evaluated in patients with symptomatic carotid stenosis who underwent filter-protected CAS or CEA procedure. Cerebral embolization, presence of neurologicals symptoms, plaque neovascularization were evaluated testing imaging, serological and histological methods. Results were compared by Fisher’s, Student T test and Mann-Whitney U test. Results. Patients with hsCRP<5 mg/l, SAA<10mg/L and VEGF<500pg/ml had a mean PO of 21.5% versus 35.3% (p<0.05). In either group, embolic material captured by the filter was identified as atherosclerotic plaque fragments. Cerebral lesions increased significantly in all patients with hsCRP>5mg/l and SAA>10mg/l (16.5 vs 2.8 mean number, 3564.6 vs 417.6 mm3 mean volume). Discussion. High hsCRP, SAA and VEGF levels are associated with significantly greater embolization during CAS and to the vulnerabiliy of the plaque. This data suggest CAS might not be indicated as a method of revascularization in this specific group of patients.

The vulnerable carotid plaque. Identification of endothelial markers predictive of plaque weakness, rupture predisposition and neoangiogenesis

Background. Neoangiogenesis is crucial in plaque progression and instability. Previous data from our group demonstrated that intra-plaque neovessels show both a Nestin+/WT+ and a Nestin+/WT1- phenotype, the latter being correlated with complications and plaque instability. Aims. The aims of the present thesis are: (i) to confirm our previous results on Nestin/WT1 phenotype in a larger series of carotid atheromatous plaques, (ii) to evaluate the relationship between the Nestin+/WT1- neoangiogenesis phenotype and plaque morphology, (iii) to evaluate the relationship between the immunohistochemical and histopathological characteristics and the clinical instability of the plaques. Materials and Methods. Seventy-three patients (53 males, 20 females, mean age 71 years) were consecutively enrolled. Symptoms, brain CT scan, 14 histological variables, including intraplaque hemorrhage and diffuse calcifications, were collected. Immunohistochemistry for CD34, Nestin and WT1 was performed. RT-PCR was performed to evaluate Nestin and WT1 mRNA (including 5 healthy arteries as controls). Results. Diffusely calcified plaques (13 out of 73) were found predominantly in females (P=0.017), with a significantly lower incidence of symptoms (TIA/stroke) and brain focal lesions (P=0.019 and P=0.013 respectively) than not-calcified plaques, but with the same incidence of intraplaque complications (P=0.156). Accordingly, both calcified and not calcified plaques showed similar mean densities of positivity for CD34, Nestin and WT1. The density of Nestin and WT1 correlated with the occurrence of intra-plaque hemorrhage in all cases, while the density of CD34 correlated only in not-calcified plaques. Conclusions. We confirmed that the Nestin+/WT1- phenotype characterizes the neovessels of instable plaques, regardless the real amount of CD34-positive neoangiogenesis. The calcified plaques show the same incidence of histological complications, albeit they do not influence symptomatology and plaque vulnerability. Female patients show a much higher incidence of not-complicated or calcified plaques, receiving de facto a sort of protection compared to male patients.

Identificazione di markers morfologici e sierologici di vulnerabilità della placca carotidea

Introduzione: L’indicazione alla rivascolarizzazione carotidea è comunemente posta in base alla percentuale di stenosi, alla presenza di sintomi neurologici ed alle condizioni cliniche del paziente. Una placca ad elevato potenziale embolico viene definita “vulnerabile”; la sua caratterizzazione, tuttavia, non è universalmente accettata ai fini della rivascolarizzazione. Lo scopo dello studio è indagare il ruolo del mezzo di contrasto ecografico (CEUS) nell’identificazione della placca carotidea vulnerabile. Materiali e Metodi: I pazienti sottoposti a endoarterectomia carotidea, sono stati valutati mediante TC cerebrale preoperatoria e CEUS. Le microbolle di contrasto rilevate nella placca, indicative di neovascolarizzazione, sono state quantificate in dB-E ed istologicamente valutate per cinque caratteristiche: (densità dei microvasi, spessore del cappuccio fibroso, estensione delle calcificazioni, infiltrato infiammatorio e core lipidico) il valore da 1 a 5, ottenuto in cieco, indica in grado di vulnerabilità della placca. L'ANOVA test, il test di Fisher e t Student sono stati usati per correlare le caratteristiche dei pazienti ed istologiche col valore di dB-E. Risultati: Di 22 pazienti (range 2-7.8, media 4.85 ±1.9 SD) vi era un numero più alto di sintomatici (7.40 ± 0.5) rispetto agli asintomatici (3.5 ± 1.4) (p = 0.002). Un più alto valore di dB-E si associava con la presenza di un sottile cappuccino fibroso (<200 µm, 5.96±1.5 vs. 3 ± 1,p = 0.01) ed un maggiore infiltrato infiammatorio (3.2 ± 0.9 vs. 6.4 ± 1.2, p = 0.03). Placche con vulnerabilità 5 si associavano ad un valore più alto di dB-E rispetto alle placche con vulnerabilità 1 (7.6 ± 0.2 vs. 2.5 ± 0.6, rispettivamente, p=0.001). Preoperatoriamente, le lesioni emboliche ipsilaterali alla TC, correlavano con un più alto valore di dB-E (5.96±1.5 vs. 3.0±1.0, p=0.01). Conclusioni: Il valore di dB-E alla CEUS indica l’estensione della neovascolarizzazione della placca carotidea e può essere utilizzato come marker di vulnerabilità della placca.

Development of Clinical Decision Support Systems based on Mathematical Models of Physiological Systems

In the last years of research, I focused my studies on different physiological problems. Together with my supervisors, I developed/improved different mathematical models in order to create valid tools useful for a better understanding of important clinical issues. The aim of all this work is to develop tools for learning and understanding cardiac and cerebrovascular physiology as well as pathology, generating research questions and developing clinical decision support systems useful for intensive care unit patients. I. ICP-model Designed for Medical Education We developed a comprehensive cerebral blood flow and intracranial pressure model to simulate and study the complex interactions in cerebrovascular dynamics caused by multiple simultaneous alterations, including normal and abnormal functional states of auto-regulation of the brain. Individual published equations (derived from prior animal and human studies) were implemented into a comprehensive simulation program. Included in the normal physiological modelling was: intracranial pressure, cerebral blood flow, blood pressure, and carbon dioxide (CO2) partial pressure. We also added external and pathological perturbations, such as head up position and intracranial haemorrhage. The model performed clinically realistically given inputs of published traumatized patients, and cases encountered by clinicians. The pulsatile nature of the output graphics was easy for clinicians to interpret. The manoeuvres simulated include changes of basic physiological inputs (e.g. blood pressure, central venous pressure, CO2 tension, head up position, and respiratory effects on vascular pressures) as well as pathological inputs (e.g. acute intracranial bleeding, and obstruction of cerebrospinal outflow). Based on the results, we believe the model would be useful to teach complex relationships of brain haemodynamics and study clinical research questions such as the optimal head-up position, the effects of intracranial haemorrhage on cerebral haemodynamics, as well as the best CO2 concentration to reach the optimal compromise between intracranial pressure and perfusion. We believe this model would be useful for both beginners and advanced learners. It could be used by practicing clinicians to model individual patients (entering the effects of needed clinical manipulations, and then running the model to test for optimal combinations of therapeutic manoeuvres). II. A Heterogeneous Cerebrovascular Mathematical Model Cerebrovascular pathologies are extremely complex, due to the multitude of factors acting simultaneously on cerebral haemodynamics. In this work, the mathematical model of cerebral haemodynamics and intracranial pressure dynamics, described in the point I, is extended to account for heterogeneity in cerebral blood flow. The model includes the Circle of Willis, six regional districts independently regulated by autoregulation and CO2 reactivity, distal cortical anastomoses, venous circulation, the cerebrospinal fluid circulation, and the intracranial pressure-volume relationship. Results agree with data in the literature and highlight the existence of a monotonic relationship between transient hyperemic response and the autoregulation gain. During unilateral internal carotid artery stenosis, local blood flow regulation is progressively lost in the ipsilateral territory with the presence of a steal phenomenon, while the anterior communicating artery plays the major role to redistribute the available blood flow. Conversely, distal collateral circulation plays a major role during unilateral occlusion of the middle cerebral artery. In conclusion, the model is able to reproduce several different pathological conditions characterized by heterogeneity in cerebrovascular haemodynamics and can not only explain generalized results in terms of physiological mechanisms involved, but also, by individualizing parameters, may represent a valuable tool to help with difficult clinical decisions. III. Effect of Cushing Response on Systemic Arterial Pressure. During cerebral hypoxic conditions, the sympathetic system causes an increase in arterial pressure (Cushing response), creating a link between the cerebral and the systemic circulation. This work investigates the complex relationships among cerebrovascular dynamics, intracranial pressure, Cushing response, and short-term systemic regulation, during plateau waves, by means of an original mathematical model. The model incorporates the pulsating heart, the pulmonary circulation and the systemic circulation, with an accurate description of the cerebral circulation and the intracranial pressure dynamics (same model as in the first paragraph). Various regulatory mechanisms are included: cerebral autoregulation, local blood flow control by oxygen (O2) and/or CO2 changes, sympathetic and vagal regulation of cardiovascular parameters by several reflex mechanisms (chemoreceptors, lung-stretch receptors, baroreceptors). The Cushing response has been described assuming a dramatic increase in sympathetic activity to vessels during a fall in brain O2 delivery. With this assumption, the model is able to simulate the cardiovascular effects experimentally observed when intracranial pressure is artificially elevated and maintained at constant level (arterial pressure increase and bradicardia). According to the model, these effects arise from the interaction between the Cushing response and the baroreflex response (secondary to arterial pressure increase). Then, patients with severe head injury have been simulated by reducing intracranial compliance and cerebrospinal fluid reabsorption. With these changes, oscillations with plateau waves developed. In these conditions, model results indicate that the Cushing response may have both positive effects, reducing the duration of the plateau phase via an increase in cerebral perfusion pressure, and negative effects, increasing the intracranial pressure plateau level, with a risk of greater compression of the cerebral vessels. This model may be of value to assist clinicians in finding the balance between clinical benefits of the Cushing response and its shortcomings. IV. Comprehensive Cardiopulmonary Simulation Model for the Analysis of Hypercapnic Respiratory Failure We developed a new comprehensive cardiopulmonary model that takes into account the mutual interactions between the cardiovascular and the respiratory systems along with their short-term regulatory mechanisms. The model includes the heart, systemic and pulmonary circulations, lung mechanics, gas exchange and transport equations, and cardio-ventilatory control. Results show good agreement with published patient data in case of normoxic and hyperoxic hypercapnia simulations. In particular, simulations predict a moderate increase in mean systemic arterial pressure and heart rate, with almost no change in cardiac output, paralleled by a relevant increase in minute ventilation, tidal volume and respiratory rate. The model can represent a valid tool for clinical practice and medical research, providing an alternative way to experience-based clinical decisions. In conclusion, models are not only capable of summarizing current knowledge, but also identifying missing knowledge. In the former case they can serve as training aids for teaching the operation of complex systems, especially if the model can be used to demonstrate the outcome of experiments. In the latter case they generate experiments to be performed to gather the missing data.

Valutazione dei disturbi cognitivi nei pazienti sottoposti a Rivascolarizzazione Carotidea (Endoarterectomia vs Stenting) mediante dosaggio di marker di danno neuronale, Mini Mental State Examination e Risonanza Magnetica

Scopo del nostro studio è quello di valutare i disturbi cognitivi in relazione al tasso di microembolia cerebrale in due gruppi di pazienti trattati per lesione carotidea asintomatica con endoarterectomia (CEA) o stenting (CAS). Comparando le due metodiche mediante l’utilizzo di risonanza magnetica in diffusione (DW-MRI), neuromarkers (NSE e S100β) e test neuropsicometrici. MATERIALE E METODI: 60 pazienti sono stati sottoposti a rivascolarizzazione carotidea (CEA n=32 e CAS n=28). Sono stati tutti valutati con DW-MRI e Mini-Mental State Examination (MMSE) test nel preoperatorio, a 24 ore, a 6 ed a 12 mesi dall’intervento. In tutti sono stati dosati i livelli sierici di NSE e S100β mediante 5 prelievi seriati nel tempo, quello basale nel preoperatorio, l’ultimo a 24 ore. L’ananlisi statistica è stata effettuata con test t di Student per confronti multipli per valori continui e con test χ2 quadro e Fisher per le variabili categoriche. Significatività P <0,05. RISULTATI: Non vi è stato alcun decesso. Un paziente del gruppo CAS ha presentato un ictus ischemico. In 6 pazienti CAS ed in 1 paziente CEA si sono osservate nuove lesioni subcliniche alla RMN-DWI post-operatoria (21,4% vs 3% p=0,03). Nel gruppo CAS le nuove lesioni presenti alla RMN sono risultate significativamente associate ad un declino del punteggio del MMSE (p=0,001). L’analisi dei livelli di NSE e S100β ha mostrato un significativo aumento a 24 ore nei pazienti CAS (P = .02). A 12 mesi i pazienti che avevano presentato nuove lesioni ischemiche nel post-operatorio hanno mostrato minor punteggio al MMSE, non statisticamente significativo. CONCLUSIONI: I neuromarkers in combinazione con MMSE e RMN-DWI possono essere utilizzati nella valutazione del declino cognitivo correlato a lesioni silenti nell’immediato postoperatorio di rivascolarizzazione carotidea. Quest’ultime dovrebbero essere valutate quindi non solo rispetto al tasso di mortalità e ictus, ma anche rispetto al tasso di microembolia.

Il craniofaringioma nel bambino e nell'adolescente. Luci ed ombre durante il follow-up

Introduction. Craniopharyngioma (CF) is a malformation of the hypothalamicpituitary region and it is the most common nonglial cerebral tumor in children with an high overall survival rate. In some case severe endocrinologic and metabolic sequelae may occur during follow up. 50% of patients (pts), in particular those with radical removal of suprasellar lesions, develop intractable hyperphagia and morbid obesity, with dyslypidemia and high cardiovascular risk. We studied the auxological and metabolic features of a series of 29 patients (18 males) treated at a mean age of 7,6 years, followed up in our Centre from 1973 to 2008 with a mean follow up of 8,3 years. Patients features at the onset. 62% of pts showed as first symptoms of disease visual impairment and neurological disturbancies (headache); 34% growth arrest; 24% signs of raised intracranial pressure and 7% diabetes insipidus. Diagnosis. Diagnosis of CF was reached finally by TC or MRI scans which showed endo-suprasellar lesion in 23 cases and endosellar tumour in 6 cases. Treatment and outcome. 25/29 pts underwent surgical removal of CF (19 by transcranial approach and 6 by endoscopic surgery); 4 pts underwent stereotactic surgery as first line therapy. 3 pts underwent local irradiation with yttrium-90, 5 pts post surgery radiotherapy. 45% of pts needed more than one treatment procedure. Results. After CF treatment all patients suffered from 3 or more pituitary hormone deficiencies and diabetes insipidus. They underwent promptly substitutive therapy with corticosteroids, l-thyroxine and desmopressin. In 28/29 pts we found growth hormone (GH) deficiency. 20/28 pts started GH substitutive therapy and 15 pts reached final height(FH) near target height(TH). 8 pts were not GH treated for good growth velocity, even without GH, or for tumour residual. They reached in 2 cases FH over TH showing the already known phenomenon of growth without GH. 38% of patients showed BMI SDS >2 SDS at last assessment, in particular pts not GH treated (BMI 2,5 SDS) are more obese than GH treated (BMI 1,2 SDS). Lipid panel of 16 examined pts showed significative differencies among GH treated (9 pts) and not treated (7 pts) with better profile in GH treated ones for Total Cholesterol/C-HDL and C-LDL/C-HDL. We examined intima media thickness of common carotid arteries in 11 pts. 3/4 not GH treated pts showed ultrasonographic abnormalities: calcifications in 2 and plaque in 1 case. Of them 1 pt was only 12,6 years old and already showed hypothalamic obesity with hyperphagia, high HOMA index and dyslipidemia. In the GH treated group (7) we found calcifications in 1 case and a plaque in another one. GH therapy was started in the young pt with carotid calcifications, with good improvement within 6 months of treatment. 5/29 pts showed hypothalamic obesity, related to hypothalamic damage (type of surgical treatment, endo-suprasellar primitive lesion, recurrences). 48% of patients recurred during follow up ( mean time from treatment: 3 years) and underwent, in some cases up to 4 transcranial surgical treatments. GH seems not to increase recurrence rate since 40% of GH treated recurred vs 66,6% of not GH treated pts. Discussion. Our data show the extereme difficulties that occur during follow up of craniopharyngioma treated patients. GH therapy should be offered to all patients even with good growth velocity after CF treatment, to avoid dislypidemia and reduce cardiovascular risk. The optimal therapy is not completely understood and whether gross tumor removal or partial surgery is the best option remains to be decided only on one patient tumour features and hypothalamic involvement. In conclusion the gold standard treatment of CF remains complete tumour removal, when feasible, or partial resection to preserve hypothalamic function in endosuprasellar large neoplasms.

Valutazione dello spessore intima-media carotideo come fattore di rischio cardiovascolare nei pazienti affetti da psoriasi moderato-severa

Evaluation of carotid artery intima-media thickness in patients affected by psoriasis Psoriasis is associated with an increased risk of atherosclerosis. This study compared subclinical atherosclerosis, evaluating intima-media thickness the of the carotid in psoriasis vulgaris patients and healthy controls using high-resolution ultrasonography and the correlation of this parameter with other cardiovascular risk factors, like insulin resistance and dyslipidemia, METHODS: We will study 40 psoriasis patients, asymptomatic for cardiovascular diseases, and 40 healthy controls matched for age and sex. Intima-media thickness of the common carotid arteries will be measured ultrasonographically. Diabetes mellitus, hypertension, renal failure, a history of cardiovascular or cerebrovascular disease will be exclusion criteria. Subjects who are receiving lipid-lowering therapy, antihypertensive or anti-aggregant drugs, nitrates or long-term systemic steroids will be also excluded. Objective of this study is the evaluation of carotid artery intima-media thickness and its correlation with other blood cardiovascular risk factors in patients affected by psoriasis but asinptomatic for coronary comparing this data with the healthy control subjects. Considering that the presence of psoriasis is an independent risk factor for subclinical atherosclerosis, we want to consider this method of evaluation of cardiovascular risk and to control this risk to prevent IMA.

What are the components that contribute to variability in echocardiographic measurements in aortic stenosis?

INTRODUCTION Echocardiography is the standard clinical approach for quantification of the severity of aortic stenosis (AS). A comprehensive examination of its overall reproducibility and the simultaneous estimation of its variance components by multiple operators, readers, probe applications, and beats have not been undertaken. METHOD AND RESULTS Twenty-seven subjects with AS were scanned over 7 months in the echo-department by a median of 3 different operators. From each patient and each operator multiple runs of beats from multiple probe positions were stored for later analysis by multiple readers. The coefficient of variation was 13.3%, 15.9%, 17.6%, and 20.2% for the aortic peak velocity (Vmax), and velocity time integral (VTI), and left ventricular outflow tract (LVOT) Vmax and VTI respectively. The largest individual contributors to the overall variability were the beat-to-beat variability (9.0%, 9.3%, 9.5%, 9.4% respectively) and that of inability of an individual operator to precisely apply the probe to the same position twice (8.3%, 9.4%, 12.9%, 10.7% respectively). The tracing (inter-reader) and reader (inter-reader), and operator (inter-operator) contribution were less important. CONCLUSIONS Reproducibility of measurements in AS is poorer than often reported in the literature. The source of this variability does not appear, as traditionally believed, to result from a lack of training or operator and reader specific factors. Rather the unavoidable beat-to-beat biological variability, and the inherent impossibility of applying the ultrasound probe in exactly the same position each time are the largest contributors. Consequently, guidelines suggesting greater standardisation of procedures and further training for sonographers are unlikely to result in an improvement in precision. Clinicians themselves should be wary of relying on even three-beat averages as their expected coefficient of variance is 10.3% for the peak velocity at the aortic valve.

Balloon Aortic Valvuloplasty as Bridge-to-Decision in High Risk Patients with Severe Aortic Valve Stenosis

Background. A sizable group of patients with symptomatic aortic stenosis (AS) can undergo neither surgical aortic valve replacement (AVR) nor transcatheter aortic valve implantation (TAVI) because of clinical contraindications. The aim of this study was to assess the potential role of balloon aortic valvuloplasty (BAV) as a “bridge-to-decision” in selected patients with severe AS and potentially reversible contraindications to definitive treatment. Methods. We retrospectively enrolled 645 patients who underwent first BAV at our Institution between July 2007 and December 2012. Of these, the 202 patients (31.2%) who underwent BAV as bridge-to-decision (BTD) requiring clinical re-evaluation represented our study population. BTD patients were further subdivided in 5 groups: low left ventricular ejection fraction; mitral regurgitation grade ≥3; frailty; hemodynamic instability; comorbidity. The main objective of the study was to evaluate how BAV influenced the final treatment strategy in the whole BTD group and in its single specific subgroups. Results. Mean logistic EuroSCORE was 23.5±15.3%, mean age was 81±7 years. Mean transaortic gradient decreased from 47±17 mmHg to 33±14 mmHg. Of the 193 patients with BTD-BAV who received a second heart team evaluation, 72.5% were finally deemed eligible for definitive treatment (25.4%for AVR; 47.2% for TAVI): respectively, 96.7% of patients with left ventricular ejection fraction recovery; 70.5% of patients with mitral regurgitation reduction; 75.7% of patients who underwent BAV in clinical hemodynamic instability; 69.2% of frail patients and 68% of patients who presented relevant comorbidities. 27.5% of the study population was deemed ineligible for definitive treatment and treated with standard therapy/repeated BAV. In-hospital mortality was 4.5%, cerebrovascular accident occurred in 1% and overall vascular complications were 4% (0.5% major; 3.5% minor). Conclusions. Balloon aortic valvuloplasty should be considered as bridge-to-decision in high-risk patients with severe aortic stenosis who cannot be immediate candidates for definitive percutaneous or surgical treatment.