Physiology of exercise and heart failure treatments: cardiopulmonary exercise testing as a tool for choosing the optimal therapeutic strategy.

In the last decades, the pharmacological treatment of heart failure (HF) become more complex due to the availability of new highly effective drugs. Although the cardiovascular effects of HF therapies have been extensively described, less known are their effects on cardiopulmonary function considered as a whole, both at rest and in response to exercise. This is a 'holistic' approach to disease treatment that can be accurately evaluated by a cardiopulmonary exercise test. The aim of this paper is to assess the main differences in the effects of different drugs [angiotensin-converting enzyme (ACE)-inhibitors, Angiotensin II receptor blockers, ß-blockers, Angiotensin receptor-neprilysin inhibitors, renal sodium-glucose co-transporter 2 inhibitors, iron supplementation] on cardiopulmonary function in patients with HF, both at rest and during exercise, and to understand how these differences can be taken into account when choosing the most appropriate treatment protocol for each individual patient leading to a precision medicine approach.

The importance of re-evaluating the risk score in heart failure patients: An analysis from the Metabolic Exercise Cardiac Kidney Indexes (MECKI) score database.

BACKGROUND: The role of risk scores in heart failure (HF) management has been highlighted by international guidelines. In contrast with HF, which is intrinsically a dynamic and unstable syndrome, all its prognostic studies have been based on a single evaluation. We investigated whether time-related changes of a well-recognized risk score, the MECKI score, added prognostic value. MECKI score is based on peak VO2, VE/VCO2 slope, Na+, LVEF, MDRD and Hb. METHODS: A multi-centre retrospective study was conducted involving 660 patients who performed MECKI re-evaluation at least 6 months apart. Based on the difference between II and I evaluation of MECKI values (MECKI II - MECKI I = ∆ MECKI) the study population was divided in 2 groups: those presenting a score reduction (∆ MECKI <0, i.e. clinical improvement), vs. patients presenting an increase (∆ MECKI >0, clinical deterioration). RESULTS: The prognostic value of MECKI score is confirmed also when re-assessed during follow-up. The group with improved MECKI (366 patients) showed a better prognosis compared to patients with worsened MECKI (294 patients) (p < 0.0001). At 1st evaluation, the two groups differentiated by LVEF, VE/VCO2 slope and blood Na+ concentration, while at 2nd evaluation they differentiated in all 6 parameters considered in the score. The patients who improved MECKI score, improved in all components of the score but hemoglobin, while patients who worsened the score, worsened all parameters. CONCLUSIONS: This study shows that re-assessment of MECKI score identifies HF subjects at higher risk and that score improvement or deterioration regards several MECKI score generating parameters confirming the holistic background of HF.

Can ß-blockers influence regular daily physical activity?

BACKGROUND: In hypertension, ß-blockers have a high rate of nonadherence to treatment likely because of fatigue. METHODS: We evaluate daily physical activity and maximal exercise performance in 56 patients with hypertension (grades I-II), with and without ß-blockers (bisoprolol 10 mg or atenolol 100 mg) added to standard treatment; 48 patients completed the study. Study tests were performed after 8 weeks of antihypertensive therapy without ß blockers and after the following 8 weeks with ß-blockers. RESULTS: No significant differences between ß-blockers were observed. At office measurement, ß-blockers decreased heart rate (HR) from 78 ±â€Š9 to 62 ±â€Š7 bpm (P < 0.01) and SBP from 133 ±â€Š13 to 125 ±â€Š12 mmHg (P < 0.01). No significant changes were observed for DBP. Conversely, at ambulatory pressure monitoring DBP but not SBP decreased with ß-blockers (mean-24-h DBP 77 ±â€Š8 vs. 74 ±â€Š7 mmHg, P < 0.01). An overall reduction of daily activities and of estimated kilocalories consumption was observed as measured by a portable armband device. Of note, time with activity more than 3 METS was reduced by ß-blockers from 148.1 (83-201) to 117.9 (82-189) min (P < 0.01). Cardiopulmonary exercise (CPE) showed a preserved exercise performance unaffected by ß-blockers. CONCLUSION: In hypertension, ß-blocker treatment is associated to reduction of daily physical activity but not of maximal exercise performance.

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.

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.'

Effects of ß2-receptor stimulation by indacaterol in chronic heart failure treated with selective or non-selective ß-blockers: a randomized trial.

Alveolar ß2-receptor blockade worsens lung diffusion in heart failure (HF). This effect could be mitigated by stimulating alveolar ß2-receptors. We investigated the safety and the effects of indacaterol on lung diffusion, lung mechanics, sleep respiratory behavior, cardiac rhythm, welfare, and exercise performance in HF patients treated with a selective (bisoprolol) or a non-selective (carvedilol) ß-blocker. Study procedures were performed before and after indacaterol and placebo treatments according to a cross-over, randomized, double-blind protocol in forty-four patients (27 on bisoprolol and 17 on carvedilol). No differences between indacaterol and placebo were observed in the whole population except for a significantly higher VE/VCO2 slope and lower maximal PETCO2 during exercise with indacaterol, entirely due to the difference in the bisoprolol group (VE/VCO2 31.8 ± 5.9 vs. 28.5 ± 5.6, p < 0.0001 and maximal PETCO2 36.7 ± 5.5 vs. 37.7 ± 5.8 mmHg, p < 0.02 with indacaterol and placebo, respectively). In carvedilol, indacaterol was associated with a higher peak heart rate (119 ± 34 vs. 113 ± 30 bpm, with indacaterol and placebo) and a lower prevalence of hypopnea during sleep (3.8 [0.0;6.3] vs. 5.8 [2.9;10.5] events/hour, with indacaterol and placebo). Inhaled indacaterol is well tolerated in HF patients, it does not influence lung diffusion, and, in bisoprolol, it increases ventilation response to exercise.

Does mitral regurgitation reduce the risks of thrombosis in atrial fibrillation and flutter?

AIMS: Blood stasis is the main cause of left atrial thrombosis (LAT) in atrial tachyarrhythmias. The high-velocity flow inside the left atrium, due to mitral valve regurgitation, may prevent clot formation but the topic has never been investigated in large-scale studies. The aim of our study was to evaluate whether the presence and degree of mitral regurgitation have a protective role against LAT risk. METHODS: A total of 1302 consecutive adult patients with paroxysmal or persistent atrial fibrillation or flutter undergoing cardioversion, submitted to transesophageal echocardiography, were retrospectively enrolled in the study. The study population was divided into three groups according to the mitral regurgitation degree: absent, mild-to-moderate and severe. RESULTS: Among 1302 patients enrolled in the study, patients without mitral regurgitation were 248 (19%), those with mild-to-moderate 970 (75%), whereas 84 had severe mitral regurgitation (6%). LAT incidence was significantly lower in patients with severe mitral regurgitation compared with those with mild-to-moderate (mitral regurgitation) (2.4 vs. 8.9%, P < 0.05), and similar to subjects without mitral regurgitation (2.4%). CONCLUSION: Despite patients with severe regurgitation having clinical and echo characteristics predisposing to LAT (higher age, heart failure, higher atrial size, lower ventricular function) thrombosis prevalence was significantly lower than for those with mild-to-moderate mitral regurgitation. The percentage of LAT in severe mitral regurgitation cases was very low and similar to that of cases without regurgitation which were characterized by lower age, normal left ventricular function or other risk factors, reinforcing the hypothesis of a protecting role against atrial thrombosis of mitral regurgitation.

The alveolar to arterial oxygen partial pressure difference is associated with pulmonary diffusing capacity in heart failure patients.

In chronic heart failure (HF), the alveolar-capillary membrane undergoes a remodeling process that negatively affects gas exchange. In case of alveolar-capillary gas diffusion impairment, arterial desaturation (SaO2) is rarely observed in HF patients. At play are 3 factors: overall pulmonary diffusing capacity (assessed as lung diffusion for CO, DLCO), global O2 consumption (VO2) and alveolar (A) to arterial (a) pO2 gradient (AaDO2). In 100 consecutive stable HF patients, DLCO, resting respiratory gases and arterial blood gases were measured to determine VO2, paO2, pAO2 and AaDO2. DLCO was poorly but significantly related to AaDO2. The correlation improved after correcting AaDO2 for VO2 (p<0.001, r=0.49). Both VO2 and AaDO2 were independently associated with DLCO (p<0.001). Patients with reduced DLCO showed no differences as regards paO2 and pAO2. AaDO2/VO2 showed a higher gradient in patients with lower DLCO. AaDO2 increase and VO2 reduction allow preventing low SaO2 in HF patients with reduced DLCO. Accordingly, we suggest considering AaDO2 and VO2 combined and reporting AaDO2/VO2.

Marked sympathetic activation and baroreflex dysfunction in true resistant hypertension.

BACKGROUND: An increase in sympathetic drive to the heart and the peripheral circulation characterizes mild and severe essential hypertension. However, it remains unsettled whether sympathetic cardiovascular influences are potentiated in true resistant hypertension (RHT). METHODS: In 32 RHT patients treated with 4.6 ± 0.3 drugs (mean ± SEM) and aged 58.6 ± 2.1 years, 35 non-resistant treated hypertensives (HT) and 19 normotensive controls (NT), all age-matched with RHT, we measured clinic, 24-hour ambulatory and beat-to-beat blood pressures (BP), heart rate (HR, EKG), muscle sympathetic nerve traffic (MSNA, microneurography) and spontaneous baroreflex MSNA-sensitivity. RESULTS: BP values were markedly greater in RHT patients than in NT and HT (172.2 ± 1.7/100.7 ± 1.2 vs 132.1 ± 1.3/82.1 ± 0.9 and 135.5 ± 1.2/83.6 ± 0.9 mmHg, P < 0.01). This was paralleled by a significant and marked increase in MSNA (87.8 ± 2.0 vs 46.8 ± 2.6 and 59.3 ± 1.7 and bursts/100 heartbeats, P < 0.01). In multiple regression analysis the MSNA increase observed in RHT was significantly related to hemodynamic, hormonal and metabolic variables. It was also significantly related to plasma aldosterone values as well as spontaneous baroreflex MSNA-sensitivity, which were the variables that at the multivariate analysis were more closely related to the adrenergic activation of RHT after adjustment for confounders, including antihypertensive treatment (r(2)partial=0.04405 and r(2)partial=0.00878, P<0.05 for both). CONCLUSIONS: These data represent the first evidence that RHT is a state of marked adrenergic overdrive, greater for magnitude than that detectable in HT. They also suggest that impaired baroreflex mechanisms, along with hemodynamic and neurohumoral factors, may be responsible for the phenomenon.

Multiparametric comparison of CARvedilol, vs. NEbivolol, vs. BIsoprolol in moderate heart failure: the CARNEBI trial.

BACKGROUND: Several ß-blockers, with different pharmacological characteristics, are available for heart failure (HF) treatment. We compared Carvedilol (ß1-ß2-α-blocker), Bisoprolol (ß1-blocker), and Nebivolol (ß1-blocker, NO-releasing activity). METHODS: Sixty-one moderate HF patients completed a cross-over randomized trial, receiving, for 2 months each, Carvedilol, Nebivolol, Bisoprolol (25.6 ± 12.6, 5.0 ± 2.4 and 5.0 ± 2.4 mg daily, respectively). At the end of each period, patients underwent: clinical evaluation, laboratory testing, echocardiography, spirometry (including total DLCO and membrane diffusion), O2/CO2 chemoreceptor sensitivity, constant workload, in normoxia and hypoxia (FiO2=16%), and maximal cardiopulmonary exercise test. RESULTS: No significant differences were observed for clinical evaluation (NYHA classification, Minnesota questionnaire), laboratory findings (including kidney function and BNP), echocardiography, and lung mechanics. DLCO was lower on Carvedilol (18.3 ± 4.8*mL/min/mmHg) compared to Nebivolol (19.9 ± 5.1) and Bisoprolol (20.0 ± 5.0) due to membrane diffusion 20% reduction (*=p<0.0001). Constant workload exercise showed in hypoxia a faster VO2 kinetic and a lower ventilation with Carvedilol. Peripheral and central sensitivity to CO2 was lower in Carvedilol while response to hypoxia was higher in Bisoprolol. Ventilation efficiency (VE/VCO2 slope) was 26.9 ± 4.1* (Carvedilol), 28.8 ± 4.0 (Nebivolol), and 29.0 ± 4.4 (Bisoprolol). Peak VO2 was 15.8 ± 3.6*mL/kg/min (Carvedilol), 16.9 ± 4.1 (Nebivolol), and 16.9 ± 3.6 (Bisoprolol). CONCLUSIONS: ß-Blockers differently affect several cardiopulmonary functions. Lung diffusion and exercise performance, the former likely due to lower interference with ß2-mediated alveolar fluid clearance, were higher in Nebivolol and Bisoprolol. On the other hand, Carvedilol allowed a better ventilation efficiency during exercise, likely via a different chemoreceptor modulation. Results from this study represent the basis for identifying the best match between a specific ß-blocker and a specific HF patient.

Chronotropic incompentence and functional capacity in chronic heart failure: no role of ß-blockers and ß-blocker dose.

AIM: To assess the effect of chronotropic incompetence on functional capacity in chronic heart failure (CHF) patients, as evaluated as NYHA and peak oxygen consumption (pVO(2) ), focusing on the presence and dose of ß-blocker treatment. METHODS: Nine hundred and sixty-seven consecutive CHF patients were evaluated, 328 of whom were discarded because they failed to meet the study criteria. Of the 639 analyzed, 90 were not treated with ß-blockers whereas the other 549 were. The latter were further subdivided in high (n = 184) and low (n = 365) ß-blockers daily dose group in accordance with an arbitrary cut-off of 25 mg for carvedilol and of 5 mg for bisoprolol. Failure to achieve 80% of the percentage of maximum age predicted peak heart rate (%Max PHR) or of HR reserve (%HRR) constituted chronotropic incompetence. RESULTS: No differences were found in NYHA or pVO2 between patients with and without ß-blockers and, similarly, between high and low ß-blocker dose groups. Twenty and sixty-nine percent of not ß-blocked patients showed chronotropic incompetence according to %Max PHR and %HRR, respectively, whereas this prevalence rose to 61% and 84% in those on ß-blocker therapy. Patients taking ß-blockers without chronotropic incompetence, as inferable from both %Max PHR and %HRR, showed higher NYHA and pVO2 regardless of drug dose, whereas, in not ß-blocked patients, only %HRR revealed a difference in functional capacity. At multivariable analysis, HR increase during exercise (ΔHR) was the variable most strongly associated to pVO2 (ß: 0.572; SE: 0.008; P < 0.0001) and NYHA class (ß: -0.499; SE: 0.001; P < 0.0001). CONCLUSIONS: ΔHR is a powerful predictor of CHF severity regardless of the presence of ß-blocker therapy and of ß-blocker daily dose.

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.

Three-dimensional echocardiography in valve disease.

This review covers the role of three-dimensional (3D) echocardiography in the diagnosis of heart valve disease. Several factors have contributed to the evolution of this technique, which is currently a simple and routine method: rapid evolution in probe and computer technologies, demonstration that 3D data sets allowed more complete and accurate evaluation of cardiac structures, emerging clinical experience indicating the strong potential particularly in valve diseases, volume and function of the two ventricle measurements and several other fields. This report will review current and future applications of 3D echocardiography in mitral, aortic and tricuspid valve diseases underlying both qualitative (morphologic) and quantitative advantages of this technique.

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.

Prosthetic mitral valve thrombosis: can fluoroscopy predict the efficacy of thrombolytic treatment?

BACKGROUND: Thrombolysis (T) is an effective therapy for prosthetic valve thrombosis (PVT). Debate still exists as to which clinical or noninvasive finding best predict the result of T. The aim of the study was to investigate the role of fluoroscopy (F) to predict efficacy of T in pts with mitral PVT. METHODS: We evaluated 17 consecutive pts with bileaflet mitral PVT. F criteria for PVT were: abnormal disc motion and calculated opening angle >25 degrees. T was carried out with tissue-type plasminogen activator (tPA; 100 mg over 3 hours followed by heparin infusion for 24 hours) and was considered successful when normalization of leaflet motion and opening angle occurred. Results were evaluated according to symptom duration (<21 days, early PVT; >21 days, late PVT) and to F pattern of PVT (blocked leaflet versus hypomobile leaflet). RESULTS: F showed disc motion alteration in 24 of 34 leaflets: 8 leaflets were blocked, whereas 16 were hypomobile. Early (12.7+/-6.1 days, range 3-21) and late (113+/-114 days, range 28-365) PVT was present in 8 and 7 pts, respectively. Thrombolysis was successful in 20 of 24 leaflets. Blocked leaflet fully recovered only in early PVT (n=4) pts, whereas they remained blocked in late PVT (n=4). On the contrary, in all of the cases with hypomobile leaflet, disc motion normalized regardless duration of symptoms and extent of disc motion reduction. Interestingly, 4 leaflets with late PVT was diagnosed as blocked by trans-thoracic (TTE). F showed a residual disc movement in all: they fully recovered after T. Two pts with late PVT had both leaflets affected (1 blocked +1 hypomobile); although blocked leaflet did not respond to T, the normalization of hypomobile significantly improved clinical condition. CONCLUSIONS: F can predict result of T in mitral PVT. PVT with F evidence of hypomobile leaflet always recovers regardless of symptom duration and extent of disc motion reduction, suggesting that the small amount of thrombus needed to interfere with discs motion in bileaflet prostheses remains sensitive to T even after a long time. PVT with F evidence of blocked leaflet has a favorable response to T only in case of early PVT. Late PVT with blocked leaflet does not respond to T, suggesting a larger and stratified thrombus and the coexistence of pannus and, in our series, always required surgery. However, if a hypomobile leaflet coexists, T may be used to restore normal movement of hypomobile leaflet so that to improve patient clinical and hemodynamic condition before operation.

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.