Lucia Salvi

5B.05: MARFAN SYNDROME: ASSESSMENT OF AORTIC DISSECTION RISK BY ANALYSIS OF AORTIC VISCOELASTIC PROPERTIES.

Objective: Marfan syndrome is an autosomal dominant genetic disorder characterized by an abnormal fibrillin-1 synthesis. Aortic root dilation and dissection are the main problems affecting patients prognosis in these patients. Their pharmacological prophylaxis with losartan or with a beta-blocker counteracts the aortic root dilation, but a close follow-up is required to assess therapeutic response rate and to identify non-responders. Unfortunately genotype-phenotype studies do not allow to determine the exact risk profile in these patients and there is no reliable method to accurately predict their risk of aortic dissection. Aim of this study was to evaluate non-invasive markers for identification of Marfan patients at higher risk of aortic complications. Design and method: We studied 187 Marfan patients (identified according to 2010 Revised Ghent Criteria and positive genetic analysis), age 32.3u200a±u200a16.5 yrs (meanu200a±u200aSD). 52 patients (27.8%) had undergone surgical ascending aorta replacement (David or Bentall procedure). Central pressure curves were recorded by PulsePen tonometer, and the aortic viscoelastic aortic properties were studied by determination of carotid-femoral pulse wave velocity (PWV). Results: With reference to the age related distribution of PWV values in a normal population, defined according to Arterial-Stiffness-Collaboration, PWV mean values in Marfan patients corresponded to 60th percentile in non- operated patients and to the 67th percentile in those operated. Adult Marfan patients (nu200a=u200a146) generally displayed a low blood pressure, because of the pharmacological prophylaxis, and were compared with a population of 189 adult healthy subjects (81 males), matched by age (38u200a±u200a13 vs 38u200a±u200a16 yrs.), heart rate (64u200a±u200a9 bpm vs 64u200a±u200a11 bpm) and blood pressure (mean BPu200a=u200a78u200a±u200a9 mmHg vs 79u200a±u200a4 mmHg) values. Average PWV value was higher than in healthy controls (PWVu200a=u200a7.0u200a±u200a1.7) both in not operated (PWVu200a=u200a7.6u200a±u200a1.6; pu200a=u200a0.0003) and in operated (PWVu200a=u200a9.5u200a±u200a3.2; pu200a<u200a0.0001) Marfan patients. Among non operated patients, PWV was significantly correlated to aortic root diameters (Aortic annulus: R2u200a=u200a0.14; Valsalva sinuses: R2u200a=u200a0.22; Sinotubular junction: R2u200a=u200a0.28). Conclusions: A significant reduction of the distensibility of the aorta was found in Marfan syndrome. Further analyses are needed to assess the prognostic significance of PWV changes seen in these in these patients.

Short-Term Repeatability of Noninvasive Aortic Pulse Wave Velocity Assessment: Comparison between Methods and Devices

BACKGROUNDnAortic pulse wave velocity (PWV) is an indirect index of arterial stiffness and an independent cardiovascular risk factor. Consistency of PWV assessment over time is thus an essential feature for its clinical application. However, studies providing a comparative estimate of the reproducibility of PWV across different noninvasive devices are lacking, especially in the elderly and in individuals at high cardiovascular risk.nnnMETHODSnAimed at filling this gap, short-term repeatability of PWV, estimated with 6 different devices (Complior Analyse, PulsePen-ETT, PulsePen-ET, SphygmoCor Px/Vx, BPLab, and Mobil-O-Graph), was evaluated in 102 high cardiovascular risk patients hospitalized for suspected coronary artery disease (72 males, 65 ± 13 years). PWV was measured in a single session twice, at 15-minute interval, and its reproducibility was assessed though coefficient of variation (CV), coefficient of repeatability, and intraclass correlation coefficient.nnnRESULTSnThe CV of PWV, measured with any of these devices, was <10%. Repeatability was higher with cuff-based methods (BPLab: CV = 5.5% and Mobil-O-Graph: CV = 3.4%) than with devices measuring carotid-femoral PWV (Complior: CV = 8.2%; PulsePen-TT: CV = 8.0%; PulsePen-ETT: CV = 5.8%; and SphygmoCor: CV = 9.5%). In the latter group, PWV repeatability was lower in subjects with higher carotid-femoral PWV. The differences in PWV between repeated measurements, except for the Mobil-O-Graph, did not depend on short-term variations of mean blood pressure or heart rate.nnnCONCLUSIONSnOur study shows that the short-term repeatability of PWV measures is good but not homogenous across different devices and at different PWV values. These findings, obtained in patients at high cardiovascular risk, may be relevant when evaluating the prognostic importance of PWV.

Systolic time intervals assessed from analysis of the carotid pressure waveform

OBJECTIVEnThe timing of mechanical cardiac events is usually evaluated by conventional echocardiography as an index of cardiac systolic function and predictor of cardiovascular outcomes. We aimed to measure the systolic time intervals, namely the isovolumetric contraction time (ICT) and pre-ejection period (PEP), by arterial tonometry.nnnAPPROACHnSixty-two healthy volunteers (age 47u2009u2009±u2009u200917 years) and 42 patients with heart failure and reduced ejection fraction were enrolled (age 66u2009u2009±u2009u200914 years). Pulse waves were recorded at the carotid artery by arterial tonometry together with simultaneous aortic transvalvular flow by Doppler-echocardiography, synchronized by electrocardiographic gating. The ICT was determined from the time delay between the electrical R wave and the carotid pressure waveform, after adjustment for the pulse transit time from the aortic valve to the carotid artery site, estimated by an algorithm based on the carotid-femoral pulse wave velocity. The PEP was evaluated by adding the electrical QR duration to the ICT.nnnMAIN RESULTSnThe ICT derived from carotid pulse wave analysis was closely related to that measured by echocardiography (ru2009u2009=u2009u20090.90, pu2009u2009<u2009u20090.0001), with homogeneous distribution in Bland-Altman analysis (mean difference and 95% confidence intervalu2009u2009=u2009u20090.2 fromu2009u2009-14.2 to 14.5u2009ms). ICT and PEP were higher in cardiac patients than in healthy volunteers (pu2009u2009<u2009u20090.0001). The ratio between PEP and left ventricular ejection time was related to the ejection fraction measured with echocardiography (ru2009u2009=u2009u20090.555, pu2009u2009<u2009u20090.0001).nnnSIGNIFICANCEnThe timing of electro-mechanical cardiac events can be reliably obtained from the carotid pulse waveform and carotid-femoral PWV, evaluated using arterial tonometry. Systolic time intervals assessed with this approach showed good agreement with measurements performed with conventional echocardiography and may represent a promising additional application of arterial tonometry.

TROPONIN INCREASE AND SUBENDOCARDIAL OXYGEN SUPPLY AND DEMAND IMBALANCE IN CARDIAC AMYLOIDOSIS

Objective: The increase in serum troponin is a known peculiarity of cardiac amyloidosis (CA). The most acclaimed hypothesis to explain this phenomenon is the direct toxicity of amyloid fibrils on cardiomyocytes, but a possible subendocardial ischemia due to discrepancy between oxygen supply and demand imbalance has not been investigated yet Figure. No caption available. Design and method: 113 outpatients, attending the Pavia Amyloid Center either for suspected or already diagnosed cardiac amyloidosis were enrolled, 58 of them were affected by CA. The subendocardial viability ratio (SEVR) was used to quantify non-invasively the relationship between subendocardial oxygen supply and demand, obtained by analysing the central pressure waveform obtained with a high-fidelity applanation tonometry (PulsePen, DiaTecne, Italy) and by calculating the ratio between the diastolic and systolic pressure-time indexes. Aortic stiffness was assessed measuring carotid-femoral pulse wave velocity (PWV). Echocardiogram data were used to quantify left ventricular diastolic pressure and left ventricular mass index. The SEVR was compared to plasmatic troponin I (TnI). Results: Troponin was higher in subjects with CA then in non-affected (NCA) (pu200a<u200a0.001). There was an inverse linear correlation between troponin and SEVR (pu200a=u200a0.002). Troponin was strongly directly correlated with left ventricle mass index (LVMI) (pu200a<u200a0.001), while the correlation between TnI and PWV was not statistically significant. Both the increase in TnI and the reduction of SEVR were significantly related to low values of left ventricular ejection fraction (EF%) (pu200a<u200a0.001). The ROC curves comparing hemodynamic parameters and the SEVR showed that SEVR had a greater sensitivity and specificity (AUCu200a=u200a0.778) than EF% (AUCu200a=u200a0.765) and PWV (AUCu200a=u200a0.539) in identifying pathological troponin values. Conclusions: There is a close connection in patients with CA between troponin values and the reduction in the SEVR. Ischemic suffering, with undamaged coronary arteries, may be a cause of cardiac myocytes damage in amyloidosis. LVMI increasing with the disease progression and the presence of amorphous amyloid mass altering the microcirculation may limit myocardial perfusion. Moreover, amyloid alters the macrostructural organization of myofibrils, thus heart may need an increased energy-metabolic supply. SEVR assessment may improve the identification of subclinical myocardial damage in patients with cardiac amyloidosis.

NON-INVASIVE MEASUREMENT OF AORTIC PULSE WAVE VELOCITY: A COMPARATIVE EVALUATION OF EIGHT DEVICES

Objective: Several non-invasive devices purport to measure aortic pulse wave velocity (PWV), by applying different approaches and sensors, with the aim of evaluating cardiovascular risk. Purpose of this study is to compare the PWV measured by eight commercially available devices in patients with cardiovascular disease. Design and method: In this study, 102 patients (70% males, mean age 65u200a±u200a13 years) were enrolled among those who were going to undertake an elective cardiac catheterization study. For each patient, the following device was used to non-invasively evaluate aortic PWV, in a random order: BPLab, Complior Analyse, Mobil-O-Graph, pOpmètre, PulsePen-ET, PulsePen-ETT and SphygmoCor. Data were analyzed by computing the coefficient of the correlation (r) and determination (r2) between measured values and with age of patients. Results: The mean blood pressure, heart rate and PWV measured in the population were: 102u200a±u200a16 mmHg, 65u200a±u200a12 s-1 and 11.2u200a±u200a3.6u200am/s. Comparative data are shown in Table 1. Devices evaluating carotid-femoral PWV (Complior Analyse, PulsePen-ET, PulsePen-ETT, SphygmoCor) presented a very strong agreement between each other (ru200a>u200a0.80) and moderate correlation with the PWV measured by the Mobil-O-Graph (r 0.45 to 0.65), while a weak correlation was found between carotid-femoral PWV measurements and the BPLab or the pOpmètre (ru200a<u200a0.30). A moderate-strong relationship was found between age and cf-PWV (r2 0.20 to 0.38), whereas PWV measured by pOpmètre and BPLab showed a weak correlation with age (r2 0.05 and 0.06 respectively). On the contrary, a very strong relationship was found between Mobil-O-Graph and age (r2u200a=u200a0.90). Conclusions: Devices measuring carotid-femoral PWV, considered the gold-standard measure for aortic PWV, present a very good agreement between each other, in our population of patients with cardiovascular disease. The Mobil-O-Graph, which estimates aortic PWV from age and blood pressure values, also present a good correlation with measures of carotid-femoral PWV. The two other measuring devices (BPLab, pOpmètre) does not provide a PWV measure in agreement with carotid-femoral PWV. Our results support the use of devices measuring carotid-femoral PWV for a proper and consistent evaluation of aortic PWV.

AORTIC VISCOELASTIC PROPERTIES AND ALTERED ELECTROMECHANICAL CARDIO-AORTIC CONNECTION IN PATIENTS WITH CARDIAC AMYLOIDOSIS

Objective: Cardiac amyloidosis (CA) is an infiltrative disorder caused by deposition of amyloid fibrils in the myocardial extracellular matrix. Although there is a wide scientific literature regarding amyloid heart disease, no data about aortic viscoelastic properties in these patients are available. This studio has the aims to start filling this gap. Figure. No caption available. Design and method: 113 outpatients attending the Pavia Amyloid Center either with suspected or already diagnosed amyloidosis were enrolled; 58 of them were affected by cardiac amyloidosis. Arterial applanation tonometry (PulsePen, DiaTecne, Milan, Italy) was performed in carotid and femoral arteries to calculate carotid-to-femoral pulse wave velocity (PWV) as index of aortic stiffness. Carotid pressure wave was calibrated with oscillometric brachial blood pressure (BP) to obtain central BP, pulse pressure amplification (PPA) and augmentation index (AIx). Tonometric data were related to biochemical parameters, clinical data and treatment. Populations with and without cardiac involvement (NCA) were compared. Results: Carotid-femoral PWV was not significantly higher in CA subjects compared to NCA (pu200a=u200a0.462). PPA was significantly reduced in subjects with CA (26.9u200a±u200a10.6% in NCA, 19.8u200a±u200a12.4% in CA, pu200a=u200a0.0014). Multivariate Regression Analysis highlighted that the presence of cardiac involvement is the main element in determining a reduction in PPA. CA subjects had lower both peripheral pressure values and central ones. There were no significant differences in central pulse pressure (42.6u200a±u200a12.3 in NCA vs 39.5u200a±u200a12.6 mmHg in CA, pu200a=u200a0.187), and AIx. The morphological analysis of the central pulse wave in its components (direct and reflected wave) did not show significant differences in the parameters studied, with the exception of Ti, detecting an early wave overlap in CA. Conclusions: Although there were no significant differences in aortic stiffness evaluated by PWV in subjects with CA, a reduced PPA was found. An altered electromechanical cardio-aortic connection, with preserved aortic properties, may be an explanation for this finding. In other words, amyloid cardiopathy strongly impairs cardiac function without significantly alteration in aortic function. Significantly reduced central and peripheral pressure values could be caused by the inability of the diseased heart to develop a post load compared to that of subjects without cardiac involvement.

COMPARISON BETWEEN AORTIC PULSE WAVE VELOCITY MEASURED INVASIVELY AND NON-INVASIVELY BY EIGHT DIFFERENT DEVICES

Objective: Aortic pulse wave velocity (PWV) is the best indicator of aortic viscoelastic properties. Aim of this study is to investigate if invasively measured aortic PWV is accurately estimated by non-invasive methods which purport to assess it. Design and method: One-hundred and two patients (30% female, mean age 65u200a±u200a13 years) planned to undertake a cardiac catheterization were enrolled in the study. Different non-invasive methods were evaluated for each subject by randomly alternating the following devices: BPLab, Complior Analyse, Mobil-O-Graph, pOpmètre, PulsePen-ET, PulsePen-ETT and SphygmoCor. Immediately after, aortic PWV was evaluated by aortic catheterization and simultaneous measurement of pressure wave above the aortic valve and at the aortic bifurcation (FS-Stiffcath). Invasive data were analyzed by proprietary software and compared with non-invasive PWV values by Bland-Altman analysis and paired parametric tests (for the whole population) and non-parametric tests (for quartiles of population according to PWV). Results: Devices evaluating carotid-femoral PWV (Complior Analyse, PulsePen-ET, PulsePen-ETT, SphygmoCor) and the Mobil-O-Graph presented a strong agreement with aortic invasive PWV (respectively, Pearson Ru200a=u200a0.64, 0.78, 0.71, 0.70, 0.66), while a moderate agreement was present for the BPLab and the pOpmètre (Ru200a=u200a0.23, 0.23). In the whole population, a significant underestimation of invasive PWV was present for Complior Analyse (−0.73u200am/s, pu200a=u200a0.016), SphygmoCor (−0.61u200am/s, pu200a=u200a0.024), Mobil-O-Graph (−1.01u200am/s, pu200a<u200a0.001) and pOpmètre (−1.55u200am/s, pu200a=u200a0.003). A tendency toward the overestimation of aortic PWV for lower PWV values and the underestimation of PWV for higher values was present for all devices, and was significant for the PulsePen-ET and the BPLab in the lowest quartile (PWVu200a<u200a8.5u200am/s, pu200a<u200a0.05) and for Complior Analyse, SphygmoCor, BPLab and Mobil-O-Graph for the highest quartile (PWVu200a>u200a13u200am/s, pu200a<u200a0.05). Conclusions: Devices measuring carotid-femoral PWV and the Mobil-O-Graph, which estimates aortic PWV from age and blood pressure values, present a good correlation with invasive aortic PWV in a large population with cardiovascular disease, while a less good agreement was found for other measuring devices (BPLab, pOpmètre). The underestimation of high PWV values may lead to erroneous estimation of cardiovascular risk by non-invasive devices.

Impaired central pulsatile hemodynamics in children and adolescents with Marfan syndrome

Background Marfan syndrome is characterized by aortic root dilation, beginning in childhood. Data about aortic pulsatile hemodynamics and stiffness in pediatric age are currently lacking. Methods and Results In 51 young patients with Marfan syndrome (12.0±3.3 years), carotid tonometry was performed for the measurement of central pulse pressure, pulse pressure amplification, and aortic stiffness (carotid‐femoral pulse wave velocity). Patients underwent an echocardiogram at baseline and at 1 year follow‐up and a genetic evaluation. Pathogenetic fibrillin‐1 mutations were classified between “dominant negative” and “haploinsufficient.” The hemodynamic parameters of patients were compared with those of 80 sex, age, blood pressure, and heart‐rate matched controls. Central pulse pressure was significantly higher (38.3±12.3 versus 33.6±7.8 mm Hg; P=0.009), and pulse pressure amplification was significantly reduced in Marfan than controls (17.9±15.3% versus 32.3±17.4%; P<0.0001). Pulse wave velocity was not significantly different between Marfan and controls (4.98±1.00 versus 4.75±0.67 m/s). In the Marfan group, central pulse pressure and pulse pressure amplification were independently associated with aortic diameter at the sinuses of Valsalva (respectively, β=0.371, P=0.010; β=−0.271, P=0.026). No significant difference in hemodynamic parameters was found according to fibrillin‐1 genotype. Patients who increased aortic Z‐scores at 1‐year follow‐up presented a higher central pulse pressure than the remaining (42.7±14.2 versus 32.3±5.9 mm Hg; P=0.004). Conclusions Central pulse pressure and pulse pressure amplification were impaired in pediatric Marfan syndrome, and associated with aortic root diameters, whereas aortic pulse wave velocity was similar to that of a general pediatric population. An increased central pulse pressure was present among patients whose aortic dilatation worsened at 1‐year follow‐up.

[PP.09.25] DEVICES FOR THE NON-INVASIVE ASSESSMENT OF AORTIC PULSE WAVE VELOCITY: EVALUATION OF SHORT-TERM REPEATABILITY

Objective: Aortic pulse wave velocity (PWV) is a validated indicator of central arterial stiffness and cardiovascular risk. We aimed to compare the repeatability of PWV measures obtained with non-invasive devices. Design and method: We evaluated the repeatibility of non-invasive measures of PWV, obtained with 4 devices measuring two-points carotid-femoral PWV (Complior, PulsePen ETT, PulsePen ET, SphygmoCor), and with 2 devices estimating PWV from the oscillometric cuff-derived brachial pulsewave (BPLab, Mobil-O-Graph). 102 patients planned to undertake a cardiac catheterization (age 65u200a±u200a13 years, 70.6% males) were enrolled. Repeated measures of PWV were obtained with all devices in a single session, 15 minutes apart. Duplicate PWV and carotid-femoral PTT measurements were compared using different indices. Coefficients of variation (CV%) and their confidence intervals (CI) are reported. Results: Devices evaluating carotid-femoral PWV showed a good repeatability (CV%[CI] for Complior: 8.8[7.3–10.1]; PulsePen ETT: 8.0[6.2–9.5]; PulsePen ET: 5.8[4.9–6.6]; SphygmoCor: 9.5[7.7–11.0]), whereas the repeatability of PWV estimated by cuff-based devices was slightly higher (BPLab: 5.5[4.2–6.6], Mobil-O-Graph: 3.4[2.9–3.8]). A lower repeatability of carotid-femoral PWV was present for greater arterial stiffness values (CV%[CI] for PWV<10u200am/s vs PWV>=10u200am/s: Complior 7.0[5.4–8.3] vs 10.5[8.0–12.5], PulsePen ETT 6.3[3.6–8.1] vs 9.2[6.5–11.3], PulsePen ET 4.9[3.5–6.0] vs 6.5[5.3–7.6], Sphygmocor 8.5[5.7–10.6] vs 10.3[7.7–12.3]. No such difference was observed with cuff-based devices (BPLab 6.0[3.6–7.7] vs 5.1[3.5–6.4], Mobil-O-Graph 3.5[2.8–4.1] vs 3.2[2.6–3.7]). Differences between repeated PWV measurements were not correlated with concomitant blood pressure (R2: 0.005) or heart rate differences (R2: 0.013). Conclusions: Short-term repeatability of PWV measures was good but not homogenous among different devices. A greater repeatability was observed with cuff-based devices, compared to devices measuring carotid-femoral PWV. This is probably due for Mobil-O-Graph to the algorithm for PWV assessment, which considers age and mean blood pressure, and for BPLab to the automated editing procedure which eliminates highly variable PWV values. Repeatability of PWV is not influenced by blood pressure or heart rate concomitant changes. For carotid-femoral PWV, the repeatability of measures is lower for higher PWV values. These results could be usefully considered when assessing PWV in a clinical setting.

Central diastolic pressure exponential decay constant and subendocardial flow supply

A n imbalance between myocardial oxygen supply and demand represents a possible cause of myocardial ischemia, even in the absence of atherosclerotic coronary artery disease. In such a perspective, the term ‘type 2 myocardial infarction’ has been proposed [1]. This is a relatively common condition, especially in the elderly [2], in critically ill patients, in patients undergoing major noncardiac surgery [3–5] and may be a cause of myocardial ischemia in patients under acute high-altitude exposure [6,7]. The incidence of myocardial infarction ‘type 2’ and of myocardial injury due to this pathogenetic mechanism tends to increase with age; after the age of 75, this type of myocardial infarction is more frequent than ‘type 1’ (i.e. the myocardial infarction related to intraluminal thrombus in coronary arteries [2]. Despite its relatively high incidence in clinical practice, the occurrence of myocardial injury due to this mechanism is often difficult to face and manage by physicians, including cardiologists and internists, as little is known about the specific etiopathogenetic mechanisms that trigger this type of myocardial damage. Moreover, there are virtually no universally adopted methods to noninvasively assess the relationship between oxygen myocardial demand and supply in clinical practice. With the aim to fill this gap, a useful index was introduced by Buckberg and Hoffman at the beginning of the 1970s known as subendocardial viability ratio (SEVR) [8,9]. This index reflected the subendocardial oxygen supply and demand ratio and was defined invasively by analyzing left ventricular (LV) and aortic pressure curves. The introduction of transcutaneous arterial tonometry has provided, albeit with major limitation [10,11], a new approach to noninvasively determine the subendocardial oxygen