ADONHERS (Aged DONor HEart Rescue by Stress Echo) National Protocol: Recipient's Survival after 10-Year Follow-Up.

Background: The gold-standard treatment for end-stage heart failure is heart transplantation, but the lack of organ donors remains an important limitation in this field. An accurate selection of marginal hearts is fundamental to increase organ availability. Purpose: In our study we analyzed if recipients receiving marginal donor (MD) hearts, selected by dipyridamole stress echocardiography according to the ADOHERS national protocol, had different outcomes compared to recipients with acceptable donor (AD) hearts. Methods: Data were collected and retrospectively analyzed from patients who received an orthotopic heart transplant at our institution between 2006 and 2014. Dipyridamole stress echo was performed on identified marginal donors and selected hearts were eventually transplanted. Clinical, laboratory and instrumental features of the recipients were evaluated and patients with homogenous baseline characteristics were selected. Results: Eleven recipients transplanted with a selected marginal heart and eleven recipients transplanted with an acceptable heart were included. Mean donor age was 41 ± 23. The median follow-up was 113 months (IQR 86-146 months). Age, cardiovascular risk and morpho-functional characteristics of the left ventricle were comparable between the two populations (p > 0.05). Left atrial size was significantly higher in patients with marginal hearts (acceptable atrial volume: 23 ± 5 mL; marginal atrial volume: 38 ± 5 mL; p = 0.003). Acceptable donor recipients showed a higher impact of Cardiac Allograph Vasculopathy (p = 0.019). No rejection differences were found between the two groups. Four patients deceased, three were standard donor recipients and one was from the marginal donor group. Conclusions: Our study shows how cardiac transplant (Htx) from selected marginal donor hearts through a non-invasive bedside technique can alleviate the shortage of organs without a difference in survival compared to acceptable donor hearts.

Feasibility and value of two-dimensional volumetric stress echocardiography.

BACKGROUND: Stroke volume response during stress is a major determinant of functional status in heart failure and can be measured by two-dimensional (2-D) volumetric stress echocardiography (SE). The present study hypothesis is that SE may identify mechanisms underlying the change in stroke volume by measuring preload reserve through end-diastolic volume (EDV) and left ventricular contractile reserve (LVCR) with systolic blood pressure and end-systolic volume (ESV). METHODS: We enrolled 4735 patients (age 63.6±11.3 years, 2800 male) referred to SE for known or suspected coronary artery disease (CAD) and/or heart failure (HF) in 21 SE laboratories in 8 countries. In addition to regional wall motion abnormalities (RWMA), force was measured at rest and peak stress as the ratio of systolic blood pressure by cuff sphygmomanometer/ESV by 2D with Simpson's or linear method. Abnormal values of LVCR (peak/rest) based on force were ≤1.10 for dipyridamole (N.=1992 patients) and adenosine (N.=18); ≤2.0 for exercise (N.=2087) or dobutamine (N.=638). RESULTS: Force-based LVCR was obtained in all 4735 patients. Lack of stroke volume increase during stress was due to either abnormal LVCR and/or blunted preload reserve, and 57% of patients with abnormal LVCR nevertheless showed increase in stroke volume. CONCLUSIONS: Volumetric SE is highly feasible with all stresses, and more frequently impaired in presence of ischemic RWMA, absence of viability and reduced coronary flow velocity reserve. It identifies an altered stroke volume response due to reduced preload and/or contractile reserve.

Hemodynamic Heterogeneity of Reduced Cardiac Reserve Unmasked by Volumetric Exercise Echocardiography.

BACKGROUND: Two-dimensional volumetric exercise stress echocardiography (ESE) provides an integrated view of left ventricular (LV) preload reserve through end-diastolic volume (EDV) and LV contractile reserve (LVCR) through end-systolic volume (ESV) changes. PURPOSE: To assess the dependence of cardiac reserve upon LVCR, EDV, and heart rate (HR) during ESE. METHODS: We prospectively performed semi-supine bicycle or treadmill ESE in 1344 patients (age 59.8 ± 11.4 years; ejection fraction = 63 ± 8%) referred for known or suspected coronary artery disease. All patients had negative ESE by wall motion criteria. EDV and ESV were measured by biplane Simpson rule with 2-dimensional echocardiography. Cardiac index reserve was identified by peak-rest value. LVCR was the stress-rest ratio of force (systolic blood pressure by cuff sphygmomanometer/ESV, abnormal values ≤2.0). Preload reserve was defined by an increase in EDV. Cardiac index was calculated as stroke volume index * HR (by EKG). HR reserve (stress/rest ratio) <1.85 identified chronotropic incompetence. RESULTS: Of the 1344 patients, 448 were in the lowest tertile of cardiac index reserve with stress. Of them, 303 (67.6%) achieved HR reserve <1.85; 252 (56.3%) had an abnormal LVCR and 341 (76.1%) a reduction of preload reserve, with 446 patients (99.6%) showing ≥1 abnormality. At binary logistic regression analysis, reduced preload reserve (odds ratio [OR]: 5.610; 95% confidence intervals [CI]: 4.025 to 7.821), chronotropic incompetence (OR: 3.923, 95% CI: 2.915 to 5.279), and abnormal LVCR (OR: 1.579; 95% CI: 1.105 to 2.259) were independently associated with lowest tertile of cardiac index reserve at peak stress. CONCLUSIONS: Heart rate assessment and volumetric echocardiography during ESE identify the heterogeneity of hemodynamic phenotypes of impaired chronotropic, preload or LVCR underlying a reduced cardiac reserve.

The prognostic value of stroke work/end-diastolic volume ratio during stress echocardiography.

BACKGROUND: The ventricular stroke work (SW) refers to the work done by the left ventricle to eject the volume of blood during one cardiac cycle. The cath-lab relationship between SW and end-diastolic volume (EDV) is the preload-recruitable SW (PRSW). Recently a non-invasive single-beat PRSW (SBPRSW) has been proposed. However, the single beat formula needs mathematical skillness, and extra software. Aim of this study was to compare the non-invasive SBPRSW with the simpler non-invasive SW/EDVratio in the stress-echo lab. METHODS: We studied 692 patients, age 62 ± 12 years, ejection fraction 50 ± 17%, with negative stress echo (SE)(exercise, n = 130, dobutamine, n = 124, dipyridamole, n = 438) and follow-up data. The PRSW was estimated at rest and at peak stress by the SBPRSW technique and compared with the SW/EDV. All patients were followed-up. Event rates were estimated with Kaplan-Meier curves. RESULTS: SBPRSW and SW/EDV were linearly correlated at rest (r = 0.842, p < .001) and at peak stress (r = 0.860, p < .001). During a median follow-up of 20 months (first quartile 8, third quartile 40 months), 132 major events were registered: at receiver operating characteristic (ROC) analysis rest SBPRSW vs. SW/EDV (AUC 0.691 vs. 0.722) and peak stress (AUC 0.744 vs. 0.800) demonstrated both a significant prognostic power (all p < .001) with non-inferior survival prediction of the simpler SW/EDV ratio at Kaplan-Meier curves (Chi-square rest = 38, peak = 56) vs. SBPRSW (Chi-square rest = 14, peak = 42). CONCLUSIONS: The data obtained with the non-invasive SBPRSW and by the simpler SW/EDV are highly comparable. PRSW with either SB or SW/EDV approach is effective in predicting follow-up events.

Heart rate reserve during dipyridamole stress test applied to potential heart donors in brain death.

BACKGROUND: A blunted heart rate reserve (HRR) during dipyridamole stress echocardiography (DSE) is a prognostically unfavorable sign of cardiac autonomic dysfunction. Short-term adjustments of heart rate (HR) are thought to rise from changes in neural input to the heart. DSE is applied in potential heart donors to rule out underlying coronary artery disease and left ventricular dysfunction. The aim of this study is to assess HRR during DSE in brain death. METHODS: We enrolled two groups: group 1 (N.=49, 22 men, 54.6±8.8 years) with patients in brain death enrolled in the nationwide marginal donor heart recruiting program; group 2 (N.=49, 18 men, 66.4±12.0 years) referred to DSE for suspected or known coronary artery disease. All underwent DSE (0.84 mg/kg in 6') by quality-controlled readers certified via web-based training (1487/CE Lazio-1). We assessed left ventricular contractile reserve (LVCR) as stress/rest ratio of force (systolic blood pressure/end-systolic volume). HRR was calculated as the peak/rest HR ratio from 12-lead EKG. RESULTS: The two study groups were similar for prevalence of inducible ischemia (4/49 vs. 9/49, P=NS). Group 1 showed higher resting HR (group 1: 88.1±15.5 bpm vs. group 2: 66.5±11.5 bpm, P<0.01) and similar peak HR (group 1: 94.7±15.3 bpm vs. group 2: 89.5±19.3 bpm, P=0.144), with blunted HRR (group 1: 1.08±0.10 bpm vs. group 2: 1.36±0.31 bpm, P<0.01). HRR was unrelated to LVCR. CONCLUSIONS: HRR is almost abolished and unrelated to LVCR in brain-dead patients during DSE. The modulation of neural input to the heart is essential to determine HRR, and plays no significant role in determining the inotropic response during DSE.

The value of a simplified approach to end-systolic volume measurement for assessment of left ventricular contractile reserve during stress-echocardiography.

The peak stress/rest ratio of left ventricular (LV) elastance, or LV force, is a load-independent index of left ventricular contractile reserve (LVCR) with stress echo (SE). To assess the accuracy of LVCR calculated during SE with approaches of different complexity. Two-hundred-forty patients were referred to SE for known or suspected coronary artery disease or heart failure and, of those, 200 patients, age 61 ± 15, 99 females, with interpretable volumetric SE were enrolled. All readers had passed the upstream quality control reading for regional wall motion abnormality (RWMA) and end-systolic volume (ESV) measurement. The employed stress was dipyridamole (0.84 mg, 6 min) in 86 (43%) and dobutamine (up to 40 mcg/kg/min) in 114 (57%) patients. All underwent SE with evaluation of RWMA and simultaneous LVCR assessment with stress/rest ratio of LV force (systolic blood pressure by cuff sphygmomanometer/ESV). ESV was calculated in each patient by two of three methods: biplane Simpson rule (S, in 100 patients), single plane area-length (AL, apical four-chamber area and length, in 100 patients), and Teichholz rule (T, from parasternal long axis and/or short axis view, in 200 patients). RMWA were observed in 54 patients. Success rate for ESV measurement was 76% (100/131) for S, 92% (100/109) for AL, and 100% (240/240) for T. There were 100 paired measurements (rest and stress) with S versus T, and 100 with AL versus T. The analysis time was the shortest for T (33 ± 8 s at rest, 34 ± 7 s at stress), intermediate for AL (70 ± 22 s at rest 67 ± 21 s at stress), and the longest for S (136 ± 24 at rest 129 ± 27 s at stress, p < 0.05 vs. T and AL). ESV absolute values were moderately correlated: T versus S (r rest = 0.746, p < 0.01, n = 100; r stress = 0.794, p < 0.01, n = 100); T vs. AL (r = 0.603 p < 0.01, n = 100, at rest and r = 0.820 p < 0.01 n = 100 at peak stress). LVCR values were tightly correlated independently of the method employed: T versus S (r = 0.899, p < 0.01, n = 100), and T versus AL (r = 0.845, p < 0.01, n = 100). LVCR can be accurately determined with all three methods used to extract the raw values of ESV necessary to generate the calculation of Force. Although S is known to be more precise in determining absolute ESV values, the relative (rest-stress) changes can be assessed, with comparable accuracy, with simpler and more feasible T and AL methods, characterized by higher success rate, shorter imaging and analysis time.

Left ventricular contractile reserve in stress echocardiography: the bright side of the force.

Stress echocardiography (SE) is based on the detection of regional wall motion abnormalities (RWMA) mirroring a physiologi-cally critical epicardial artery stenosis which determines subendocardial underperfusion. Recently, the core protocol of SE has been enriched by the addition of left ventricular contractile reserve (LVCR) based on force. Changes in force can be caused by microvascular and/or epicardial coronary artery disease, but also by myocardial scar, necrosis, and/or sub-epicardial layer disease. Left ventricular contractile reserve is calculated as the stress-to-rest ratio of force (systolic arterial pressure measured by cuff sphygmomanometer to end-systolic volume determined by two-dimensional echocardiography). In contrast to the ejection fraction, force is not dependent on changes in preload and afterload. Cut-off values for a preserved LVCR are > 2.0 for dobu-tamine or exercise stress and > 1.1 for vasodilators, which are weaker inotropic stimuli. Patients with a "strong" heart (normal LVCR values) have a better outcome than patients with a "weak" heart (reduced LVCR values), and this is the prognostic "bright side of the force," meaning that the prognostic value of force-based contractile reserve is higher than that of ejection fraction-based contractile reserve or RWMA. The addition of force to standard SE based on RWMA detection increases the spectrum of risk stratification without any signifi-cant increase in imaging time and only a slight increase in analysis time. In both ischaemic (with RWMA) and non-ischaemic (without RWMA) hearts, the preserved force is associated with a more benign prognosis. The prospective multicentre interna-tional Stress Echo 2020 trial which started in September 2016 has already recruited > 5000 patients with dual RWMA-force imaging and will systematically test the impact of force on the prognosis within and beyond coronary artery disease, including heart failure and hypertrophic cardiomyopathy.

Integration of Wall Motion, Coronary Flow Velocity, and Left Ventricular Contractile Reserve in a Single Test: Prognostic Value of Vasodilator Stress Echocardiography in Patients with Diabetes.

BACKGROUND: Coronary flow velocity reserve (CFVR) and left ventricular contractile reserve (LVCR) have demonstrated prognostic importance in patients with diabetes. The aim of this study was to investigate the prognostic contribution of combined evaluation of CFVR and LVCR in patients with diabetes with nonischemic stress echocardiography. METHODS: Three hundred seventy-five patients with diabetes (mean age, 68 ± 9 years) with nonischemic dipyridamole stress echocardiography underwent assessment of CFVR of the left anterior descending coronary artery (prospectively) and LVCR with left ventricular force (retrospectively) in a multicenter study. RESULTS: On receiver operating characteristic analysis, LVCR ≤ 1.1 was the best prognostic predictor and was considered an abnormal value. CFVR was abnormal (≤2) in 139 patients (37%), LVCR in 156 (42%), neither in 157 (42%), and both in 77 (21%). During a median follow-up period of 16 months, 86 major adverse cardiac events occurred: 16 deaths, 13 myocardial infarctions, and 57 revascularizations. Multivariate prognostic indicators were CFVR ≤ 2 (P < .0001), age (P = .03), and LVCR ≤ 1.1 (P = .04). The 3-year rate of major adverse cardiac events was 63% in patients with both abnormal CFVR and LVCR, 42% in those with abnormal CFVR only, 19% in those with abnormal LVCR only, and 10% in patients with both normal CFVR and LVCR. The 3-year hard event rate was 3% in patients with both normal CFVR and LVCR, fivefold higher in patients with abnormal CFVR or LVCR only, and ninefold higher in patients with both abnormal CFVR and LVCR. CONCLUSIONS: Patients with diabetes with nonischemic dipyridamole stress echocardiography may still have significant risk in presence of abnormal CFVR and/or LVCR, which assess the underlying, largely unrelated, microvascular and myocardial components of coronary circulation.

Relación presión/volumen en el laboratorio de ecocardiografía de estrés. ¿Cómo influye el tamaño del ventrículo izquierdo (dimensión diastólica del ventrículo izquierdo)? / Pressure-volume relationship in the stress-echocardiography laboratory: Does (left ventricular end-diastolic) size matter?

Introducción y objetivos: La variación en la relación presión/volumen telesistólica entre el reposo y el estrés máximo es un índice de contractilidad del ventrículo izquierdo independiente de la poscarga. Aún no está claro si depende del volumen telediastólico y hasta qué punto. El objetivo de este estudio es evaluar la dependencia de la variación de la relación presión/volumen telesistólica entre el reposo y estrés (Δ) y el volumen telediastólico en pacientes con ecocardiografía de estrés negativa y con todos los intervalos de función ventricular izquierda en reposo. Métodos: Analizamos los datos interpretables obtenidos de 891 pacientes (593 varones; 63 ± 12 años) con fracción de eyección del 47 ± 12%: 338 pacientes estaban sanos, prácticamente sanos o hipertensos; 229 tenían arteriopatía coronaria y 324, miocardiopatía dilatada isquémica o no isquémica. Se los estudió con ecocardiografía de estrés en ejercicio (n =172), dipiridamol (n = 482) o dobutamina (n = 237). La relación presión/volumen telesistólica se evaluó en reposo y en estrés máximo a partir de una medición bruta de la presión arterial sistólica mediante esfigmógrafo con manguito y el volumen telesistólico, por ecocardiografía bidimensional mediante el método de Simpson biplanar. Resultados: Los valores absolutos de la variación reposo-estrés en la relación presión/volumen telesistólica fueron más altos con ejercicio y dobutamina que con dipiridamol. En la población general, se observó relación inversa entre la relación presión/volumen telesistólica y el volumen telediastólico en reposo (r2 = 0,69; p < 0,001) y en estrés máximo (r2 = 0,56; p < 0,001), pero no se observó esta relación al considerar la variación reposo-estrés de la relación presión/volumen telesistólica (r2 = 0,13). Conclusiones: El volumen telediastólico ventricular izquierdo no afecta a la variación reposo-estrés de la relación presión/volumen telesistólica en ventrículos izquierdos normales o anómalos durante el estrés físico o farmacológico (AU)

Introduction and objectives: The variation between rest and peak stress end-systolic pressure-volume relation is an afterload-independent index of left ventricular contractility. Whether and to what extent it depends on end-diastolic volume remains unclear. The aim of this study was to assess the dependence of the delta rest-stress end-systolic pressure-volume relation on end-diastolic volume in patients with negative stress echo and all ranges of resting left ventricular function. Methods: We analyzed interpretable data obtained in 891 patients (593 men, age 63 ± 12 years) with ejection fraction 47% ± 12%: 338 were normal or near-normal or hypertensive; 229 patients had coronary artery disease; and 324 patients had ischemic or nonischemic dilated cardiomyopathy. They were studied with exercise (n = 172), dipyridamole (n = 482) or dobutamine (n = 237) stress echocardiography. The end-systolic pressure-volume relation was evaluated at rest and peak stress from raw measurement of systolic arterial pressure by cuff sphygmomanometer and end-systolic volume by biplane Simpson rule dimensional echocardiography. Results: Absolute values of delta rest-stress end-systolic pressure-volume relation were higher for exercise and dobutamine than for dipyridamole. In the overall population, an inverse relationship between end-systolic pressure-volume relation and end-diastolic volume was present at rest (r2 = 0.69, P < .001) and peak stress (r2 = 0.56, P < .001), but was absent if the delta rest-stress end-systolic pressure-volume relation was considered (r2 = 0.13). Conclusions: Left ventricular end-diastolic volume does not affect the rest-stress changes in end-systolic pressure-volume relation in either normal or abnormal left ventricles during physical or pharmacological stress (AU)

Pressure-volume Relationship in the Stress-echocardiography Laboratory: Does (Left Ventricular End-diastolic) Size Matter?

INTRODUCTION AND OBJECTIVES: The variation between rest and peak stress end-systolic pressure-volume relation is an afterload-independent index of left ventricular contractility. Whether and to what extent it depends on end-diastolic volume remains unclear. The aim of this study was to assess the dependence of the delta rest-stress end-systolic pressure-volume relation on end-diastolic volume in patients with negative stress echo and all ranges of resting left ventricular function. METHODS: We analyzed interpretable data obtained in 891 patients (593 men, age 63 ± 12 years) with ejection fraction 47% ± 12%: 338 were normal or near-normal or hypertensive; 229 patients had coronary artery disease; and 324 patients had ischemic or nonischemic dilated cardiomyopathy. They were studied with exercise (n = 172), dipyridamole (n = 482) or dobutamine (n = 237) stress echocardiography. The end-systolic pressure-volume relation was evaluated at rest and peak stress from raw measurement of systolic arterial pressure by cuff sphygmomanometer and end-systolic volume by biplane Simpson rule 2-dimensional echocardiography. RESULTS: Absolute values of delta rest-stress end-systolic pressure-volume relation were higher for exercise and dobutamine than for dipyridamole. In the overall population, an inverse relationship between end-systolic pressure-volume relation and end-diastolic volume was present at rest (r2 = 0.69, P < .001) and peak stress (r2 = 0.56, P < .001), but was absent if the delta rest-stress end-systolic pressure-volume relation was considered (r2 = 0.13). CONCLUSIONS: Left ventricular end-diastolic volume does not affect the rest-stress changes in end-systolic pressure-volume relation in either normal or abnormal left ventricles during physical or pharmacological stress.

Medium-term outcome of recipients of marginal donor hearts selected with new stress-echocardiographic techniques over standard criteria.

BACKGROUND: Heart transplantation is limited by severe donor organ shortage. Regardless of the changes made in the acceptance of marginal donors, any such mechanism cannot be considered successful unless recipient graft survival rates remain acceptable. A stress echo-driven selection of donors has proven successful in older donors with normal left ventricular resting function and in standard donors with reversible resting left ventricular dysfunction acutely improving during stress, or slowly improving (over hours) during intensive hormonal treatment. Aim of this study is to assess the medium-term outcome of recipients of marginal donor hearts selected with new echocardiographic techniques over standard criteria. METHODS AND RESULTS: We enrolled 43 recipients of marginal donor hearts: age > 55 years, or < 55 years but with concomitant risk factors, n = 32; acutely improving during stress, n = 3; or slowly improving during hormonal treatment, n = 8. At follow-up (median, 30 months; interquartile range, 21-52 months), 37 of the recipients were still alive. One-year survival was 93%. CONCLUSION: The strict use of new stress-echocardiographic techniques over standard criteria of marginal donor management, together with comprehensive monitoring of the donor, has the potential to substantially increase the number of donor hearts without adverse effects on recipient medium-term outcome.

Myocardial contractility in the stress echo lab: from pathophysiological toy to clinical tool.

Up-regulation of Ca2+ entry through Ca2+ channels by high rates of beating is involved in the frequency-dependent regulation of contractility: this process is crucial in adaptation to exercise and stress and is universally known as force-frequency relation (FFR). Disturbances in calcium handling play a central role in the disturbed contractile function in myocardial failure. Measurements of twitch tension in isolated left-ventricular strips from explanted cardiomyopathic hearts compared with non-failing hearts show flat or biphasic FFR, while it is up-sloping in normal hearts. Starting in 2003 we introduced the FFR measurement in the stress echo lab using the end-systolic pressure (ESP)/End-systolic volume index (ESVi) ratio (the Suga index) at increasing heart rates. We studied a total of 2,031 patients reported in peer-reviewed journals: 483 during exercise, 34 with pacing, 850 with dobutamine and 664 during dipyridamole stress echo. We demonstrated the feasibility of FFR in the stress echo lab, the clinical usefulness of FFR for diagnosing latent contractile dysfunction in apparently normal hearts, and residual contractile reserve in dilated idiopathic and ischemic cardiomyopathy. In 400 patients with left ventricular dysfunction (ejection fraction 30 ± 9%) with negative stress echocardiography results, event-free survival was higher (p < 0.001) in patients with ΔESPVR (the difference between peak and rest end-systolic pressure-volume ratio, ESPVR) ≥ 0.4 mmHg/mL/m2. The prognostic stratification of patients was better with FFR, beyond the standard LV ejection fraction evaluation, also in the particular settings of severe mitral regurgitation or diabetics without stress-induced ischemia. In the particular setting of selection of heart transplant donors, the stress echo FFR was able to correctly select 34 marginal donor hearts efficiently transplanted in emergency recipients. Starting in 2007, we introduced an operator-independent cutaneous sensor to monitor the FFR: the force is quantified as the sensed pre-ejection myocardial vibration amplitude. We demonstrated that the sensor-derived force changes at increasing heart rates are highly related with both max dP/dt in animal models, and with the stress echo FFR in 220 humans, opening a new window for pervasive cardiac heart failure monitoring in telemedicine systems.

End-systolic elastance and ventricular-arterial coupling reserve predict cardiac events in patients with negative stress echocardiography.

BACKGROUND: A maximal negative stress echo identifies a low-risk subset for coronary events. However, the potentially prognostically relevant information on cardiovascular hemodynamics for heart-failure-related events is unsettled. Aim of this study was to assess the prognostic value of stress-induced variation in cardiovascular hemodynamics in patients with negative stress echocardiography. METHODS: We enrolled 891 patients (593 males mean age 63 ± 12, ejection fraction 48 ± 17%), with negative (exercise 172, dipyridamole 482, and dobutamine 237) stress echocardiography result. During stress we assessed left ventricular end-systolic elastance index (E(LV)I), ventricular arterial coupling (VAC) indexed by the ratio of the E(LV)I to arterial elastance index (E aI), systemic vascular resistance (SVR), and pressure-volume area (PVA). Changes from rest to peak stress (reserve) were tested as predictors of main outcome measures: combined death and heart failure hospitalization. RESULTS: During a median followup of 19 months (interquartile range 8-36), 50 deaths and 84 hospitalization occurred. Receiver-operating-characteristic curves identified as best predictors E(LV)I reserve for exercise (AUC = 0.871) and dobutamine (AUC = 0.848) and VAC reserve (AUC = 0.696) for dipyridamole. CONCLUSIONS: Patients with negative stress echocardiography may experience an adverse outcome, which can be identified by assessment of E(LV)I reserve and VAC reserve during stress echo.

Transplant of stunned donor hearts rescued by pharmacological stress echocardiography: a "proof of concept" report.

BACKGROUND: Due to the shortage of donor hearts, the criteria for acceptance have been considerably expanded. Hearts with regional or global left ventricular dysfunction are excluded from donation, but stress echo might be useful to identify patients with reversible wall motion abnormalities, potentially eligible for donation. METHODS: Six marginal candidate donors (mean age, 40 ± 13 years; three men) were enrolled. Resting echocardiography showed in all subjects a LV ejection fraction ≥ 45% (mean 51 ± 5%), but multiple risk factors were present. All donors had either global or discrete wall motion abnormalities: Wall Motion Score Index (WMSI) rest = 1.33 ± 0.25. Stress echocardiography was performed with the dipyridamole high dose of 0.84 mg/kg given over 6 min. RESULTS: The stress echo results were abnormal in three donors (WMSI rest = 1.51 ± 0.19 vs peak = 1.41 ± 0.30). These hearts were excluded from donation and cardiac pathology verification was available in two cases of confirmed LV myocardial fibrosis and/or severe coronary stenosis. The remaining three hearts improved during stress (WMSI rest = 1.15 ± 0.13 vs peak = 1.04 ± 0.06) and were transplanted uneventfully. Recipients (three males, mean age 53 ± 4 years) underwent post-TX coronary angiography, IVUS and endomyocardial biopsies. No recipient had primary graft failure, and all showed normal coronary angiography and normal LV function (EF = 57 ± 6%; WMSI = 1 ± 0) at 1-month post-TX. The recipients were alive at 12-month median follow-up. CONCLUSIONS: Dipyridamole stress echo performed in brain-dead potential donors with LV resting global or discrete wall motion abnormalities identifies hearts with severe morphologic abnormalities excluded from donation (with fixed response during stress echo) from hearts eligible for donation, showing improvement in regional wall motion during stress (viability response) and normal function and coronary anatomy following transplantation.

Real time 3D echocardiography (RT3D) for assessment of ventricular and vascular function in hypertensive and heart failure patients.

BACKGROUND: Cardiac and systemic hemodynamics have been historically in the domain of invasive cardiology, but recent advances in real-time 3-Dimensional echocardiography (RT3D echo) provide a reliable measurement of ventricular volumes, allowing to measure a set of hemodynamic parameters previously difficult or impossible to obtain with standard 2D echo. AIM: To assess the feasibility of a comprehensive hemodynamic study with RT-3D echo. METHODS: We enrolled 136 patients referred for routine echocardiography: 44 normal (N), 57 hypertensive (HYP), and 35 systolic heart failure patients (HF). All patients underwent standard 2D echo examination followed by RT3D echo examination, including measurement of left ventricular (LV) end-diastolic and end-systolic volumes and derived assessment of LV elastance (an index of LV contractility), arterial elastance (characterizing the distal impedance of the arterial system downstream of the aortic valve); ventricular-arterial coupling (a central determinant of net cardiovascular performance); systemic vascular resistances. Blood pressure was derived from cuff sphygmomanometer and heart rate from ECG. RESULTS: A complete 2D echo was performed in all 136 patients. 3D echo examination was obtained in 130 patients (feasibility = 95 %). Standard 2D echo examination was completed in 14.8 ± 2.2 min. Acquisition of 3D images required an average time of 5 ± 0.9 min (range 3.5-7.5 min) and image analysis was completed in 10.1 ± 2.8 min (range 6-12 min) per patient. Compared to N and HYP, HF patients showed reduced LV elastance (1.7 ± 1.5 mmHg mL(-1) m(-2), p < 0.001 vs N = 3.8 ± 1.3 and HYP = 3.8 ± 1.3) and ventricular-arterial coupling (0.6 ± 0.5, p < 0.01 vs N = 1.4 ± 0.4 and HYP = 1.2 ± 0.4). Systemic vascular resistances were highest in HYP (2736 ± 720, p < .01 vs N = 1980 ± 432 and vs HF = 1855 ± 636 dyne*s/cm5). The LV elastance was related to EF (r = 0.73, p < 0.01) and arterial pressure was moderately related to vascular elastance (r = 0.54, p < 0.01). The ventricular-arterial coupling was unrelated to systemic vascular resistances (r = -0.04, p NS). CONCLUSION: RT-3D echo allows a non invasive, comprehensive assessment of cardiac and systemic hemodynamics, offering insight access to key variables--such as increased systemic vascular resistances in hypertensives and reduced ventricular-arterial coupling in heart failure patients.

Wait, treat and see: echocardiographic monitoring of brain-dead potential donors with stunned heart.

BACKGROUND: Heart transplantation is limited by a severe donor organ shortage. Potential donors with brain death (BD) and left ventricular dysfunction due to neurogenic stunning are currently excluded from donation--although such abnormalities can be reversible with aggressive treatment including Hormonal Treatment (HT) and deferred organ retrieval. AIM: To assess the recovery of left ventricular dysfunction in potential brain-dead donors with hemodynamic instability treated by aggressive treatment and HT. METHODS: In a single-center, observational study design, we evaluated 15 consecutive brain-dead potential donors (DBD) (8 males, age = 48 ± 15 years) with hemodynamic instability. All underwent standard hemodynamic monitoring and transthoracic 2-dimensional echo (2-DE) with assessment of Ejection Fraction (EF). Measurements were obtained before BD and after BD within 6 h, at 24 h and within 48 h. HT (with insulin, methylprednisolone, vasopressin and T3) was started as soon as possible to treat hemodynamic instability and avoid administration of norepinephrine (NE). Eligible potential heart donors underwent coronary angiography. RESULTS: After HT, we observed a normalization of hemodynamic conditions with improvement of mean arterial pressure (pre = 68 ± 8 mmHg vs post = 83 ± 13 mmHg, p < .01), cardiac index (pre = 2.4 ± 0.6 L/min/m2 vs post 3.7 ± 1.2 L/min/m2, p < .05), EF (pre = 48 ± 15 vs post = 59 ± 3%, p < .01) without administration of norepinephrine (NE) in 67% of cases. Five potential donors were excluded from donation (opposition, n = 3, tubercolosis n = 1, malignancy n = 1). At pre-harvesting angiography, coronary artery stenosis was present in 2 of the 10 consented donors. Eight hearts were uneventfully transplanted. No early graft failure occurred and all eight recipients were alive at 6-month follow-up. CONCLUSION: In BD donors, intensive treatment including HT is associated with improvement of regional and global LV function and reverse remodeling detectable by transthoracic 2DE. Donor hearts with recovered LV function may be eligible for uneventful heart transplant. The wait (in brain death), treat (with HT) and see (with 2D echo) strategy can help rescue organs suitable for heart donation.

Abnormal shortened diastolic time length at increasing heart rates in patients with abnormal exercise-induced increase in pulmonary artery pressure.

BACKGROUND: The degree of pulmonary hypertension is not independently related to the severity of left ventricular systolic dysfunction but is frequently associated with diastolic filling abnormalities. The aim of this study was to assess diastolic times at increasing heart rates in normal and in patients with and without abnormal exercise-induced increase in pulmonary artery pressure (PASP). METHODS: We enrolled 109 patients (78 males, age 62 ± 13 years) referred for exercise stress echocardiography and 16 controls. The PASP was derived from the tricuspid Doppler tracing. A cut-off value of PASP ≥ 50 mmHg at peak stress was considered as indicative of abnormal increase in PASP. Diastolic times and the diastolic/systolic time ratio were recorded by a precordial cutaneous force sensor based on a linear accelerometer. RESULTS: At baseline, PASP was 30 ± 5 mmHg in patients and 25 ± 4 in controls. At peak stress the PASP was normal in 95 patients (Group 1); 14 patients (Group 2) showed an abnormal increase in PASP (from 35 ± 4 to 62 ± 12 mmHg; P < 0.01). At 100 bpm, an abnormal (< 1) diastolic/systolic time ratio was found in 0/16 (0%) controls, in 12/93 (13%) Group 1 and 7/14 (50%) Group 2 patients (p < 0.05 between groups). CONCLUSION: The first and second heart sound vibrations non-invasively monitored by a force sensor are useful for continuously assessing diastolic time during exercise. Exercise-induced abnormal PASP was associated with reduced diastolic time at heart rates beyond 100 beats per minute.