Dynamic trend of lung fluid movement during exercise in heart failure: From lung imaging to alveolar-capillary membrane function.

BACKGROUND: In chronic heart failure (HF), exercise-induced increase in pulmonary capillary pressure may cause an increase of pulmonary congestion, or the development of pulmonary oedema. We sought to assess in HF patients the exercise-induced intra-thoracic fluid movements, by measuring plasma brain natriuretic peptide (BNP), lung comets and lung diffusion for carbon monoxide (DLCO) and nitric oxide (DLNO), as markers of hemodynamic load changes, interstitial space and alveolar-capillary membrane fluids, respectively. METHODS AND RESULTS: Twenty-four reduced ejection fraction HF patients underwent BNP, lung comets and DLCO/DLNO measurements before, at peak and 1 h after the end of a maximal cardiopulmonary exercise test. BNP significantly increased at peak from 549 (328-841) to 691 (382-1207, p < 0.0001) pg/mL and almost completely returned to baseline value 1 h after exercise. Comets number increased at peak from 9.4 ± 8.2 to 24.3 ± 16.7, returning to baseline (9.7 ± 7.4) after 1 h (p < 0.0001). DLCO did not change significantly at peak (from 18.01 ± 4.72 to 18.22 ± 4.73 mL/min/mmHg), but was significantly reduced at 1 h (16.97 ± 4.26 mL/min/mmHg) compared to both baseline (p = 0.0211) and peak (p = 0.0174). DLNO showed a not significant trend toward lower values 1 h post-exercise. CONCLUSIONS: Moderate/severe HF patients have a 2-step intra-thoracic fluid movement with exercise: the first during active exercise, from the vascular space toward the interstitial space, as confirmed by comets increase, without any effect on diffusion, and the second, during recovery, toward the alveolar-capillary membrane, clearing the interstitial space but worsening gas diffusion.

Why Levosimendan Improves the Clinical Condition of Patients With Advanced Heart Failure: A Holistic Approach.

BACKGROUND: In advanced heart failure (HF), levosimendan increases peak oxygen uptake (VO2). We investigated whether peak VO2 increase is linked to cardiovascular, respiratory, or muscular performance changes. METHODS AND RESULTS: Twenty patients hospitalized for advanced HF underwent, before and shortly after levosimendan infusion, 2 different cardiopulmonary exercise tests: (a) a personalized ramp protocol with repeated arterial blood gas analysis and standard spirometry including alveolar-capillary gas diffusion measurements at rest and at peak exercise, and (b) a step incremental workload cardiopulmonary exercise testing with continuous near-infrared spectroscopy analysis and cardiac output assessment by bioelectrical impedance analysis.Levosimendan significantly decreased natriuretic peptides, improved peak VO2 (11.3 [interquartile range 10.1-12.8] to 12.6 [10.2-14.4] mL/kg/min, P < .01) and decreased minute ventilation to carbon dioxide production relationship slope (47.7 ± 10.7 to 43.4 ± 8.1, P < .01). In parallel, spirometry showed only a minor increase in forced expiratory volume, whereas the peak exercise dead space ventilation was unchanged. However, during exercise, a smaller edema formation was observed after levosimendan infusion, as inferable from the changes in diffusion components, that is, the membrane diffusion and capillary volume. The end-tidal pressure of CO2 during the isocapnic buffering period increased after levosimendan (from 28 ± 3 mm Hg to 31 ± 2 mm Hg, P < .01). During exercise, cardiac output increased in parallel with VO2. After levosimendan, the total and oxygenated tissue hemoglobin, but not deoxygenated hemoglobin, increased in all exercise phases. CONCLUSIONS: In advanced HF, levosimendan increases peak VO2, decreases the formation of exercise-induced lung edema, increases ventilation efficiency owing to a decrease of reflex hyperventilation, and increases cardiac output and muscular oxygen delivery and extraction.

Comparison between PtCO2 and PaCO2 and Derived Parameters in Heart Failure Patients during Exercise: A Preliminary Study.

Evaluation of arterial carbon dioxide pressure (PaCO2) and dead space to tidal volume ratio (VD/VT) during exercise is important for the identification of exercise limitation causes in heart failure (HF). However, repeated sampling of arterial or arterialized ear lobe capillary blood may be clumsy. The aim of our study was to estimate PaCO2 by means of a non-invasive technique, transcutaneous PCO2 (PtCO2), and to verify the correlation between PtCO2 and PaCO2 and between their derived parameters, such as VD/VT, during exercise in HF patients. 29 cardiopulmonary exercise tests (CPET) performed on a bike with a ramp protocol aimed at achieving maximal effort in ≈10 min were analyzed. PaCO2 and PtCO2 values were collected at rest and every 2 min during active pedaling. The uncertainty of PCO2 and VD/VT measurements were determined by analyzing the error between the two methods. The accuracy of PtCO2 measurements vs. PaCO2 decreases towards the end of exercise. Therefore, a correction to PtCO2 that keeps into account the time of the measurement was implemented with a multiple regression model. PtCO2 and VD/VT changes at 6, 8 and 10 min vs. 2 min data were evaluated before and after PtCO2 correction. PtCO2 overestimates PaCO2 for high timestamps (median error 2.45, IQR -0.635-5.405, at 10 min vs. 2 min, p-value = 0.011), while the error is negligible after correction (median error 0.50, IQR = -2.21-3.19, p-value > 0.05). The correction allows removing differences also in PCO2 and VD/VT changes. In HF patients PtCO2 is a reliable PaCO2 estimation at rest and at low exercise intensity. At high exercise intensity the overall response appears delayed but reproducible and the error can be overcome by mathematical modeling allowing an accurate estimation by PtCO2 of PaCO2 and VD/VT.

How Patients With Heart Failure Perform Daily Life Activities: An Innate Energy-Saving Strategy.

BACKGROUND: Cardiopulmonary exercise test and 6-minute walking test are frequently used tools to evaluate physical performance in heart failure (HF), but they do neither represent activities of daily living (ADLs) nor fully reproduce patients' symptoms. We assessed differences in task oxygen uptake, both as absolute value and as percentage of peak oxygen consumption (peakVO2), ventilation efficiency (VE/VCO2 ratio), and dyspnea intensity (Borg scale) in HF and healthy subjects during standard ADLs and other common physical actions. METHODS: Healthy and HF subjects (ejection fraction <45%, stable conditions) underwent cardiopulmonary exercise test. All of them, carrying a wearable metabolic cart, performed a 6-minute walking test, two 4-minute treadmill exercises (at 2 and 3 km/h), and ADLs: ADL1 (getting dressed), ADL2 (folding 8 towels), ADL3 (putting away 6 bottles), ADL4 (making a bed), ADL5 (sweeping the floor for 4 minutes), ADL6 (climbing 1 flight of stairs carrying a load). RESULTS: Sixty patients with HF (age 65.2±12.1 years; ejection fraction 30.4±6.7%, peakVO2 14.2±4.0 mL/[min·kg]) and 40 healthy volunteers (58.9±8.2 years, peakVO2 28.1±7.4 mL/[min·kg]) were enrolled. For each exercise, patients showed higher VE/VCO2 ratio, percentage of peakVO2, and Borg scale value than controls, while absolute values of task oxygen uptake and exercise duration were lower and higher, respectively, in all activities, except for treadmill (fixed execution time and intensity). Differently from Borg Scale data, metabolic values and exercise time length changed in parallel with HF severity, except for ADL duration in very short (ADL3) and composite (ADL1) activities. Borg scale values correlated with percentage of peakVO2. CONCLUSIONS: During ADLs, patients self-regulated activities in parallel with HF severity by decreasing intensity (VO2) and prolonging the effort.

Cardiac patient care during a pandemic: how to reorganise a heart failure unit at the time of COVID-19.

To date, the pandemic spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has involved over 100 countries in a matter of weeks, and Italy suffers from almost 1/3 of the dead cases worldwide. In this report, we show the strategies adopted to face the emergency at Centro Cardiologico Monzino, a mono-specialist cardiology hospital sited in the region of Italy most affected by the pandemic, and specifically we describe how we have progressively modified in a few weeks the organization of our Heart Failure Unit in order to cope with the new COVID-19 outbreak. In fact, on the background of the pandemic, cardiovascular diseases still occur frequently in the general population, but we observed consistent reduction in hospital admissions for acute cardiovascular events and a dramatic increase of late presentation acute myocardial infarction. Despite a reduction of healthcare workers number, our ward has been rearranged in order to take care of both COVID-19 and cardiovascular patients. In particular according to a triple step procedure we divided admitted patients in confirmed, suspected and excluded cases (respectively allocated in "red", "pink" and "green" separated areas). Due to the absence of definite guidelines, our aim was to describe our strategy in facing the current emergency, in order to reorganize our hospital in a dynamic and proactive manner. To quote the famous Italian writer Alessandro Manzoni 'It is less bad to be agitated in doubt than to rest in error.'

Multi-parametric "on board" evaluation of right ventricular function using three-dimensional echocardiography: feasibility and comparison to traditional two-and three dimensional echocardiographic measurements.

Three-dimensional echocardiographic (3DE) of right ventricle (RV) has been validated in many clinical settings. However, the necessity of complicated and off-line dedicated software has reduced its diffusion. A new simplified "on board" 3DE software (OB) has been developed to obtain RV volumes and ejection fraction (EF) together with several conventional parameters automatically derived from 3DE: tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), longitudinal strain (LS). Aims of this study were to evaluate feasibility and accuracy of OB RV analysis. A complete 2DE and 3DE with OB 3DRV evaluation was obtained in 35 normal subjects and 105 patients with different pathologies. Results were compared with the conventional off-line software (OFL) and with the 2D-derived corresponding values. A subgroup of 22 patients underwent also cardiac CMR. OB 3DRV was feasible in 133/140 cases (95%) in a mean time of 97.5 ± 33 s lower than OFL analysis (129 ± 52 s plus dataset loading 80 ± 24 s). Imaging quality was good in 84%. OB and OFL 3DE RV volumes and EF were similar. 3DE derived FSA and LS (but not TAPSE) were similar to 2DE values and correlated with tissue Doppler systolic peak velocity, dP/dt, systolic pulmonary pressure and myocardial performance index. OB RV volumes and EF well correlated with CMR. (bias + SD: - 21.5 ± 20 mL for EDV; - 8.2 ± 12.4 mL for ESV; - 1 ± 5.9% for EF). OB 3DE method is feasible, simple, time saving. It easily provides 3DE RV volumes and multiple functional parameters. Off-line operator border adjustment may improve accuracy of 3DE TAPSE.

Effects of beta-blockers on ventilation efficiency in heart failure.

BACKGROUND: Hyperventilation and consequent reduction of ventilation (VE) efficiency are frequently observed during exercise in heart failure (HF) patients, resulting in an increased slope of VE/carbon dioxide (VE/Vco(2)) relationship. The latter is an independent predictor of HF prognosis. beta-Blockers improve the prognosis of HF patients. We evaluated the effect on the efficiency of VE of a beta(1)-beta(2) unselective (carvedilol) versus a beta(1) selective (bisoprolol) beta-blocker. METHODS: We analyzed consecutive maximal cardiopulmonary exercise tests performed on 572 clinically stable HF patients (New York Heart Association class I-III, left ventricle ejection fraction < or =50%) categorized in 3 groups: 81 were not treated with beta-blocker, 304 were treated with carvedilol, and 187 were treated with bisoprolol. Clinical conditions were similar. RESULTS: The VE/Vco(2) slope was lower in carvedilol- compared with bisoprolol-treated patients (29.7 +/- 0.4 vs 31.6 +/- 0.5, P = .023, peak oxygen consumption adjusted) and with patients not receiving beta-blockers (31.6 +/- 0.7, P = .036). Maximum end-tidal CO(2) pressure during the isocapnic buffering period was higher in patients treated with carvedilol (39.0 +/- 0.3 mm Hg) than with bisoprolol (37.2 +/- 0.4 mm Hg, P < .001) and in patients not receiving beta-blockers (37.2 +/- 0.5 mm Hg, P = .001). CONCLUSIONS: Reduction of hyperventilation, with improvement of VE efficiency during exercise (reduction of VE/Vco(2) slope and increase of maximum end-tidal CO(2) pressure), is specific to carvedilol (beta(1)-beta(2) unselective blocker) and not to bisoprolol (beta(1)-selective blocker).

Alveolar membrane conductance decreases as BNP increases during exercise in heart failure. Rationale for BNP in the evaluation of dyspnea.

BACKGROUND: In left ventricular failure (LVF) patients, brain natriuretic peptide (BNP), lung diffusion for carbon monoxide (DLCO), and alveolar-membrane conductance (DM) correlate with LVF severity and prognosis. The reduction of DLCO and DM during exercise reflects pulmonary edema formation. METHODS AND RESULTS: To evaluate, in LVF patients, the correlation between BNP and lung diffusion parameters at rest and during exercise, we studied 17 severe LVF patients, 13 moderate, and 10 normals measuring BNP and lung diffusion parameters before, at the end, and 1 hour after a 10-minute high-intensity constant-workload exercise. At rest, a significant correlation exists between BNP and lung diffusion parameters. Resting BNP, DLCO, and DM correlate with peak oxygen consumption (P < .0001 for all analyses). With exercise, BNP increase is significant (severe LVF 180 +/- 49 pg/mL, moderate 68 +/- 58, normals 18 +/- 12); differently, only in severe LVF, with exercise, DLCO (-1.1 +/- 0.7 mL/mm Hg/min, P < .0001) and DM (-6.4 +/- 2.8, P < .0006) decrease. One hour after exercise, only in severe LVF, BNP is still higher than at rest, while DLCO, DM, and DM/Vc are lower. Significant correlations are observed between BNP and DM changes during exercise and recovery (P < .0001) in severe LVF. CONCLUSIONS: In severe LVF, BNP changes during exercise correlate with simultaneous reductions in DM, suggesting that BNP increase and pulmonary edema formation could be related.

Assessment of cardiac resynchronization therapy response.

The present study was performed to evaluate how to assess cardiac resynchronization therapy (CRT) efficacy in chronic heart failure (CHF) through clinical, echocardiographic and exercise analysis. We analyzed 41 stable CHF (NYHA III) patients with: left bundle-branch-block, ejection fraction <35%, left-ventricular dissynchrony (by tissue-Doppler), peak oxygen consumption (VO2) <16 ml/kg/min, suitable cardiac vein (by multislice computed tomography) and no anemia or kidney failure. Patients were evaluated before and after (7+/-3 months) CRT. Two patients died. CRT responders to none of the evaluated criteria were 19.5%. The best agreement (90%) with clinical response was obtained using the presence/absence of either left-ventricular systolic volume (LVSV) or peakVO2 response. In less severe CHF (peakVO2 12-16 ml/kg/min), peakVO2 and work-load didn't change after CRT, despite echocardiographic, ventilation/carbon dioxide relationship and clinical improvement. Echocardiography and CPET are complementary for the evaluation of CRT, but not in less severe CHF patients, where the role of CPET remain uncertain.

Clinical utility of guideline-based echocardiography: a prospective study of outpatient referral patterns at a tertiary care center.

BACKGROUND: The spread of echocardiography has increased the number of requests for echocardiography and the length of patient waiting lists in National Health Systems. This overuse of echocardiography may also result in a decrease in examination quality because of an excess in workload. The recommended use of guidelines for the requesting of echocardiograms could reduce the demand for this investigation and thus reduce both workload and health care costs. METHODS: In a prospective study of 520 outpatients in a large tertiary referral center, we analyzed adherence by family physicians and cardiovascular specialists to published guidelines for requesting echocardiograms; the use of a written indication justifying the request for the first and subsequent examinations; the diagnostic outcome; and the clinical utility of each echocardiogram performed. RESULTS: Most echocardiograms (72%) were requested by specialists, follow-ups were frequent (72%), and 14% of these proved normal. Among first examinations, 49% of those requested by family physicians and 36% of those requested by specialists were normal (P = not significant [NS]); in both groups 27% of the requests lacked a written indication. Family physicians requested echocardiograms chiefly for arterial hypertension, palpitations, chest pain, and valve disease, whereas specialists most often requested echocardiograms for checking valve prostheses, ischemic heart disease, and valve disease. The rate of adherence to guidelines (54% vs 52%, P = NS) and clinical utility (60% vs 61%, P = NS) was low and similar for family physicians and specialists. Provision of a written indication for the examination by the requesting physician correlated strongly to the clinical utility of the test (P < .001), and adherence of indication to guidelines was the major determinant of clinical utility at logistic regression analysis (P < .001). CONCLUSION: The rate of adherence to guidelines was lower than desirable and similar for family physicians and cardiovascular specialists. Adherence to guidelines and provision of a written specific indication strongly enhanced the value of the echocardiographic investigation.

High-grade video compression of echocardiographic studies: a multicenter validation study of selected motion pictures expert groups (MPEG)-4 algorithms.

BACKGROUND: Large files produced by standard compression algorithms slow down spread of digital and tele-echocardiography. We validated echocardiographic video high-grade compression with the new Motion Pictures Expert Groups (MPEG)-4 algorithms with a multicenter study. METHODS: Seven expert cardiologists blindly scored (5-point scale) 165 uncompressed and compressed 2-dimensional and color Doppler video clips, based on combined diagnostic content and image quality (uncompressed files as references). One digital video and 3 MPEG-4 algorithms (WM9, MV2, and DivX) were used, the latter at 3 compression levels (0%, 35%, and 60%). RESULTS: Compressed file sizes decreased from 12 to 83 MB to 0.03 to 2.3 MB (1:1051-1:26 reduction ratios). Mean SD of differences was 0.81 for intraobserver variability (uncompressed and digital video files). Compared with uncompressed files, only the DivX mean score at 35% (P = .04) and 60% (P = .001) compression was significantly reduced. At subcategory analysis, these differences were still significant for gray-scale and fundamental imaging but not for color or second harmonic tissue imaging. Original image quality, session sequence, compression grade, and bitrate were all independent determinants of mean score. CONCLUSIONS: Our study supports use of MPEG-4 algorithms to greatly reduce echocardiographic file sizes, thus facilitating archiving and transmission. Quality evaluation studies should account for the many independent variables that affect image quality grading.

Clinical validation of different echocardiographic motion pictures expert group-4 algorythms and compression levels for telemedicine.

Tele-echocardiography is not widely used because of lengthy transmission times when using standard Motion Pictures Expert Groups (MPEG)-2 lossy compression algorythms, unless expensive high bandwidth lines are used. We sought to validate the newer MPEG-4 algorythms to allow further reduction in echocardiographic motion video file size. Four cardiologists expert in echocardiography read blindly 165 randomized uncompressed and compressed 2D and color Doppler normal and pathologic motion images. One Digital Video and 3 MPEG-4 compression algorythms were tested, the latter at 3 decreasing compression quality levels (100%, 65% and 40%). Mean diagnostic and image quality scores were computed for each file and compared across the 3 compression levels using uncompressed files as controls. File dimensions decreased from a range of uncompressed 12-83 MB to MPEG-4 0.03-2.3 MB. All algorythms showed mean scores that were not significantly different from uncompressed source, except the MPEG-4 DivX algorythm at the highest selected compression (40%, p=.002). These data support the use of MPEG-4 compression to reduce echocardiographic motion image size for transmission purposes, allowing cost reduction through use of low bandwidth lines.

Effects of acute angiotensin-converting enzyme inhibition on diastolic ventricular interaction in the dilated heart.

BACKGROUND: The normal and dilated heart behaves as a single functional unit during preload reduction: volume unloading in the setting of diastolic ventricular interaction allows for increased left ventricular (LV) filling. HYPOTHESIS: We hypothesized that reduction of venous return induced by a physiologic stimulus (tilting) or by acute angiotensin-converting enzyme (ACE) inhibitors in dilated heart is likely to have a marked and similar effect on ventricular chamber geometry and filling. This study was designed to assess how the normal and dilated heart adapts to preload reduction. METHODS: Twenty normal subjects and 20 patients with moderate heart failure due to dilated cardiomyopathy were studied with two-dimensional and Doppler echocardiography in supine position (B) and after 40 degrees of head-up tilting (T). The following day, patients repeated supine (C) and tilting test (TC) after administration of captopril (25 mg s.l.). Right ventricular (RV) and LV dimensions, LV geometry, and tricuspid, mitral, and pulmonary venous flow patterns were recorded at each step of the study. RESULTS: In the two groups, T was associated with reduction of RV area and LV volumes; C and TC produced a similar effect on RV and LV. Changes in LV septal-lateral diameter and anterior-posterior diameter were different at each step of the study: during T (both groups) and after C and TC, the septallateral diameter increased slightly while the anterior-posterior diameter decreased. During T, mitral and tricuspid peak flow velocities decreased, peak late velocities were unchanged, and the deceleration time of mitral flow increased; the systolic forward flow of pulmonary venous flow decreased, the diastolic forward flow did not change, and the difference in duration between reverse pulmonary flow and mitral peak late flow decreased: C and CT induced similar changes. CONCLUSION: Preload reduction induced by tilting or by ACE inhibitors induces profound and similar effects on LV and RV dimensions, LV geometry, and biventricular filling. Reduction of RV dimension is associated with adaptation of LV geometry and decrease of LV diastolic pressure, which facilitates LV filling and pulmonary venous drainage: ACE inhibition associated with tilting exerts an additional effect on these changes. These data confirm the role of ventricular interaction in modulating LV filling in heart failure.

Initial experience with a new on-line transthoracic three-dimensional technique: assessment of feasibility and of diagnostic potential.

BACKGROUND: Despite its wide diagnostic potential, three-dimensional (3D) echocardiography is a quite rarely employed technique. The ideal method to obtain transthoracic 3D imaging is on-line 3D echocardiography, but first-generation real-time instruments had technical limitations. A new on-line 3D technology which allows true real-time volume rendering of the cardiac anatomy has been recently introduced and its feasibility and diagnostic advantages have been evaluated in the clinical setting. METHODS: The system utilizes a "matrix" transducer with a dedicated software. It allows instantaneous acquisition and rendering on-line 3D images and interactive manipulation of 3D data. Eighty-three adult patients with various cardiac pathologies underwent on-line 3D echocardiography. Long- and short-axis views of the aorta, mitral valve and left ventricle and surgical views of these structures were attempted. The duration of acquisition and reconstruction, and the quality and incremental clinical value of 3D images in comparison with two-dimensional imaging were annotated. RESULTS: The mean time of 3D examination was 10 +/- 5 min; the mean number of acquisitions was 10.8 per patient. The quality of the 3D images was optimal in 39%, good in 37%, sufficient in 19%, and insufficient in 5% of the patients. In all cases at least one optimal or good live 3D image was obtained from the parasternal and apical views. The reconstruction of surgical or en face views was easily and rapidly (1-2 min) achieved by two experts in 3D echocardiography. The additional clinical values of 3D vs two-dimensional imaging was demonstrated in 7 patients with mitral valve disease, 3 with aortic valve pathology, and 3 with congenital heart disease. Several on-line 3D images that have not correspondence with two-dimensional echocardiography were reconstructed, creating projections dedicated to the diagnostic goal. CONCLUSIONS: On-line 3D echocardiography can be easily performed in adult patients and allows for unique planes and projections. The instant rendering of 3D images facilitates the recognition of cardiac structures and increases the diagnostic potential of transthoracic echocardiography.

Echocardiographic determinants of mitral early flow propagation velocity.

Transmitral color Doppler early diastolic flow propagation velocity (Vp) has been correlated with the left ventricular (LV) relaxation time constant tau in dilated cardiomyopathy and ischemic heart disease. The aim of this study was to investigate the independent influence of LV systolic function and geometry, and of LV relaxation, on Vp in an unselected outpatient population. We studied 30 normal subjects and 130 patients (hypertensive LV hypertrophy, aortic valve stenosis or prosthesis, hypertrophic cardiomyopathy, coronary artery disease, dilated cardiomyopathy, aortic or mitral valve regurgitation). In all, we noninvasively measured LV geometry, mass, systolic function, wall motion dyssynergy, and diastolic function (abnormal relaxation or restrictive LV Doppler filling patterns). The Vp was similar in normal subjects and in patients (51 +/- 14 vs 53 +/- 25 cm/s). In normal subjects, the determinants of Vp at multiple regression analysis were isovolumic relaxation time, 2-dimensional cardiac index, and mitral E-wave velocity-time integral. In all, the main determinants were LV ejection fraction, percent of segmental wall dyssynergy, and isovolumic relaxation time and age. The Vp was highest in hypertrophic (75 +/- 25 cm/s, p <0.05 vs normal subjects) and lowest in dilated (35 +/- 13 cm/s, p = NS) cardiomyopathy. During multivariate analysis of variance, percent of wall dyssynergy (but not diffuse LV hypokinesia) independently reduced Vp (p = 0.02). The latter was not influenced by the LV filling pattern. Thus, in an unselected clinical population, prolonged relaxation per se does not influence Vp if LV systolic dysfunction and/or wall dyssynergy is absent-the latter factors are important independent determinants of Vp, which is determined by multiple factors.