Proximal pressure reducing effect of wave reflection in the pulmonary circulation disappear in obstructive disease: insight from a rabbit model.

Locating the site of increased resistance within the vascular tree in pulmonary arterial hypertension could assist in both patient diagnosis and tailoring treatment. Wave intensity analysis (WIA) is a wave analysis method that may be capable of localizing the major site of reflection within a vascular system. We investigated the contribution of WIA to the analysis of the pulmonary circulation in a rabbit model with animals subjected to variable occlusive pulmonary disease. Animals were embolized with different sized microspheres for 6 wk ( n = 10) or underwent pulmonary artery (PA) ligation for 6 wk ( n = 3). These animals were compared with a control group ( n = 6) and acutely embolized animals ( n = 4). WIA was performed and compared with impedance-based methods to analyze wave reflections. The control group showed a relatively high extent of reflected waves (15.7 ± 10.6%); reflections had a net effect of pressure reduction during systole, suggesting an open-end reflector. The pattern of wave reflection was not different in the group with partial PA ligation (12.4 ± 4.1%). In the chronically embolized group, wave reflection was not observed (3.6 ± 1.5%). In the acute embolization group, wave reflection was more prominent (37.3 ± 12.6%), with the appearance of a novel wave increasing pressure, suggesting the appearance of a closed-end reflector. Wave reflections of an open-end type are present in the normal rabbit pulmonary circulation. However, the pattern and nature of reflections vary according to the extent of pulmonary vascular occlusion. NEW & NOTEWORTHY The study proposes an original framework of a complementary analysis of wave reflections in the time domain and in the frequency domain. The methodology was used in the pulmonary circulation with different forms of chronic obstructions. The results suggest that the pulmonary vascular tree generates a reflection pattern that could actually assist the heart during ejection, and chronic obstruction significantly modifies the pattern.

Effects of the cardiac myosin activator Omecamtiv-mecarbil on severe chronic aortic regurgitation in Wistar rats.

BACKGROUND: Aortic regurgitation (AR) is a valvular disease that can lead to systolic heart failure. Treatment options besides cardiac surgery are limited and consequently severe AR is associated with higher mortality and morbidity when not operated. In this investigation, we examined the effects of a novel cardiac myosin activator, Omecamtiv-mecarbil (OM), in rats with chronic severe AR. METHODS: AR was created by retrograde puncture of the aortic valve leaflets in 20 adults Wistar rats. 12 animals survived the acute AR phase and were randomized 2 months thereafter into OM (n = 7) or placebo groups (n = 5). Two rats underwent a sham operation and served as controls. Equal volumes of OM or placebo (NaCl 0.9%) were perfused in the femoral vein by continuous infusion (1.2 mg/kg/hour) during 30 min. Doppler-echocardiography was performed before and at the end of the infusion periods. RESULTS: OM increased indices of global cardiac function (cardiac output, stroke volume), and increased systolic performance (fractional shortening, ejection fraction, left ventricular end systolic diameter) (all p < 0.05). These effects concurred with decreases in indices of LV preload (left atrial size, left ventricular end diastolic diameter) as well in the aortic pre-ejection period / left ventricular ejection time ratio (all p < 0.05). The severity score of the regurgitant AR jet did not change. Placebo infusion did not affect these parameters. CONCLUSION: The cardiac myosin activator OM exerts favorable hemodynamic effects in rats with experimental chronic AR.

Measuring pulmonary arterial compliance: mission impossible? Insights from a novel in vivo continuous-flow based experimental model.

Arterial compliance (C) is related to the elasticity, size, and geometrical distribution of arteries. Compliance is a determinant of the load that impedes ventricular ejection. Measuring compliance is difficult, particularly in the pulmonary circulation in which resistive and compliant vessels overlap. Comparing different methods for quantification of compliance to a method that involves a continuous flow might help to identify the optimal method. Pulmonary arterial compliance was computed in six pigs based on the stroke volume to pulse pressure ratio, diastolic decay exponential fitting, area method, and the pulse pressure method (PPM). Compliance measurements were compared to those obtained under continuous flow conditions through a right ventricular bypass (Heartware Inc., Miami Lakes, FL, USA). Compliance was computed for various flows using diastolic decay exponential fitting after an abrupt interruption of the pump. Under the continuous flow conditions, resistance (R) was a decreasing function of the flow, and the fitting to P = e-t/RC yielded a pulmonary time constant (RC) of 2.06 s ( ± 0.48). Compliance was an increasing function of flow. Steady flow inter-method comparisons of compliance under pulsatile flow conditions showed large discrepancies and values (7.23 ± 4.47 mL/mmHg) which were lower than those obtained under continuous flow conditions (10.19 ± 1 0.31 mL/mmHg). Best agreement with steady flow measurements is obtained with the diastolic decay method. Resistance and compliance are both flow-dependent and are inversely related in the pulmonary circulation. The dynamic nature of the pulsatile flow may induce a non-uniformly distributed compliance, with an influence on the methods of measurement.

Left ventricular assist device: exercise capacity evolution and rehabilitation added value.

BACKGROUND: With more than 15,000 implanted patients worldwide and a survival rate of 80% at 1-year and 59% at 5-years, left ventricular assist device (LVAD) implantation has become an interesting strategy in the management of heart failure patients who are resistant to other kinds of treatment. There are limited data in the literature on the change over time of exercise capacity in LVAD patients, as well as limited knowledge about the beneficial effects that rehabilitation might have on these patients. Therefore, the aim of our study was to evaluate the evolution of exercise capacity on a cohort of patients implanted with the same device (HeartWare©) and to analyse the potential impact of rehabilitation. METHODS: Sixty-two patients implanted with a LVAD between June 2011 and June 2015 were screened. Exercise capacity was evaluated by cardiopulmonary exercise testing at 6 weeks, 6 and 12 months after implantation. RESULTS: We have observed significant differences in the exercise capacity and evolution between the trained and non-trained patients. Some of the trained patients nearly normalised their exercise capacity at the end of the rehabilitation programme. CONCLUSIONS: Exercise capacity of patient implanted with a HeartWare© LVAD increased in the early period after implantation. Rehabilitation allowed implanted patients to have a significantly better evolution compared to non-rehabilitated patients.

Ten-year results of aortic valve replacement with first-generation Mitroflow bioprosthesis: is early degeneration a structural or a technical issue?

OBJECTIVES: Concerns have been raised about the durability of the first-generation Mitroflow aortic bioprosthesis (model 12 A-LX) due to the lack of anticalcification treatment. This study reflects a 10-year experience with this prosthesis for aortic valve replacement. METHODS: From June 2003 to May 2012, the Mitroflow prosthesis was used for aortic valve replacement in 510 patients, of whom only 467 with complete clinical follow-up were included for analysis. Study end-points were survival and incidence of structural valve degeneration (SVD). Analysis of SVD was based on cumulative incidence function and competing-risk Cox regression. RESULTS: The mean patient age was 76.4 ± 6.1 years. Valve sizes from 23 to 25 were used in 70.4%, whereas sizes from 19 to 21 were used in only 19.2%, thereby avoiding patient-prosthesis mismatch in 89.1%. Within a median follow-up time of 6.6 years (interquartile range 4.4), a cumulative 2375 patient-years, the survival rate was 86.2%, 67.3% and 33.3% at 1, 5 and 10 years, respectively. The cumulative incidence of SVD, with death as a competing risk, was 0%, 0.7% and 6.2% at 1, 5 and 10 years, respectively. Only age <75 years tended to affect the late hazard of SVD (hazard ratio 0.50, 95% confidence interval 0.23-1.08, P = 0.08), regardless of valve-specific issues. CONCLUSIONS: The data do not support the concerns about early accelerated structural degeneration of the first-generation Mitroflow bioprosthesis used for aortic valve replacement in patients older than 75 years. We postulate that limiting the number of small prostheses using a proper implantation technique has enhanced the reduction in risk of significant patient-prosthesis mismatch as the main determinant of early SVD.

Low target-INR anticoagulation is safe in selected aortic valve patients with the Medtronic Open Pivot mechanical prosthesis: long-term results of a propensity-matched comparison with standard anticoagulation.

OBJECTIVES: To investigate the long-term results of a low international normalized ratio (INR)-anticoagulation program in selected patients after aortic valve replacement (AVR) with the Medtronic Open Pivot mechanical heart valve (OPMHV). METHODS: From January 1993 to December 2012, 909 OPMHV valves were used for single AVR. Patients with preserved sinus rhythm and left ventricular function (Low-INR, n = 552), were managed to an INR of 1.5-2.5 and compared to patients (Standard-INR, n = 357) treated with standard anticoagulation (INR 2.5-3.5). Long-term outcome was analysed for survival and valve-related events, on propensity score matched pairs of 169 patients/group. RESULTS: Within a follow-up cumulating 3096 patient-years, 10- and 15-year survival was significantly better for Low-INR patients: 79% and 63% vs 63% and 34% ( P < 0.001). Multivariate analysis of late mortality identified older age [odds ratio (OR) = 1.05], chronic pulmonary disease (OR = 1.90) and coronary artery disease (OR = 1.57) as patient-related risk factors, and erratic INR (OR = 2.57) as anticoagulation-related factor. The linearized thromboembolic rate was 0.72%/patient-year in Low-INR patients, vs 0.87%/patient-year in Standard-INR patients ( P = 0.59), revealing INR variability as sole predictor (OR 3.54, 95% confidence interval (CI) 1.20-10.51, P = 0.022). The linearized bleeding incidence was respectively 0.61%/patient-year and 1.21%/patient-year for Low-INR and Standard-INR patients ( P = 0.04), retaining older age (OR 1.06, 95% CI 1.02-1.12, P = 0.009), hypertension (OR 2.06, 95% CI 1.00-4.25, P = 0.05) and erratic INR (OR 9.83, 95% CI 5.21-18.56, P < 0.001) as independent risk factors. CONCLUSIONS: This study demonstrated that application of an anticoagulation regimen, aiming a low INR, individualized to selected aortic OPMHV patients, is safe and effective over more than 20 years, without increasing the thromboembolic complication rate while lowering the haemorrhagic events. However, INR variability remains worrisome because of its deleterious effect on outcome.

The linear relationship between systolic pulmonary artery pressure and mean pulmonary artery pressure is maintained regardless of autonomic or rhythm disturbances.

BACKGROUND: In the pulmonary circulation, there is a linear relationship between systolic pulmonary arterial pressure (SPAP) and mean pulmonary arterial pressure (MPAP). The aim of this study was to determine the passive or active nature of this mechanism by exploring the relationship in patients with and without autonomic rhythm control of the heart and pulmonary circulation. METHODS: Pulmonary arterial pressure recordings from non-transplanted patients and patients with heart transplants or double lung transplants were retrospectively reviewed. The relationships between systolic, diastolic, and mean pulmonary arterial pressures were explored. RESULTS: A linear relationship was observed between the SPAP and MPAP, whether patients were paced (MPAP = 0.56 SPAP + 3.86 mmHg, r (2) = 0.889), treated with inotropes (MPAP = 0.55 SPAP + 5.52 mmHg, r (2) = 0.947) or pulmonary vasodilators (MPAP = 0.58 SPAP + 2.41 mmHg, r (2) = 0.927), were exercising (MPAP = 0.61 SPAP + 1.18 mmHg, r (2) = 0.967), had a heart transplant (MPAP = 0.66 SPAP +0.87 mmHg, r (2) = 0.849), a double lung transplant (MPAP = 0.7 SPAP +0.48 mmHg, r (2) = 0.915), or no intervention (MPAP = 0.59 SPAP +1.75 mmHg, r (2) = 0.937). CONCLUSION: We demonstrate that the linear relationship between SPAP and MPAP remains in several situations. Therefore, we conclude that the underlying mechanism is a passive consequence of the elastic properties of the cardiopulmonary unit.

Impact of Detergent-Based Decellularization Methods on Porcine Tissues for Heart Valve Engineering.

To date an optimal decellularization protocol of heart valve leaflets (HVL) and pericardia (PER) with an adequate preservation of the extracellular matrix (ECM) is still lacking. This study compares a 4 day Triton X-100-based protocol with faster SDC-based protocols for the decellularization of cardiac tissues. Decellularized and non-treated HVL and PER were processed for histological, biochemical and mechanical analysis to determine the effect of these agents on the structure, ECM components, and biomechanical properties. Tissues treated with SDC-based protocols still showed nuclear material, whereas tissues treated with Triton X-100 1% + ENZ ± TRYP were completely cell free. For both decellularized tissues, an almost complete washout of glycosaminoglycans, a reduction of soluble collagen and an alteration of the surface ultrastructure was observed. Interestingly, only the elastic fibers of pericardial tissue were affected and this tissue had a decreased maximum load. This study showed that both detergents had a similar impact on the ECM. However, Triton X-100 1% +DNase/RNase (ENZ) ± Trypsin (TRYP) is the only protocol that generated completely cell free bioscaffolds. Also, our study clearly demonstrated that the decellularization agents have more impact on pericardial tissues than on heart valve leaflets. Thus, for the purpose of tissue engineering of heart valves, it is advisable to use valvular rather than pericardial matrices.

How to cope with a temporarily aborted transplant program: solutions for a prolonged waiting period.

BACKGROUND: Due to budgetary restrictions our university heart transplant program came to a standstill to be gradually restarted early 2011. Consequently waiting-times for transplantation increased dramatically beyond the usual 10-15 months. We reviewed the clinical results of this peculiar transplant program over the past 4 years. METHODS: Since March 2011 until February 2015, 65 patients (age 48±23 years) were listed for heart transplantation. Eight patients (11%) of whom three in high emergency were transplanted without any form of mechanical assistance. Fifty-one patients required a left ventricular assist device (LVAD) Heartware (Heartware Inc., Miami Lakes, FL, USA) as a bridge-to-transplant due to terminal heart failure. Merely 5 listed patients remain without assistance. RESULTS: One patient without assistance and 11 LVAD patients (22%) died on the waiting-list. Meanwhile 10 LVAD patients were transplanted after a 2-year waiting time (770±717 days). Four transplanted patients died of early graft failure none after LVAD explantation. Survival at 1 and 3 years was respectively 78 (72%) and 83 (78%) for transplanted and assisted patients (log-rank P=0.056). Cox multivariable regression analysis identified crash-to-burn patients (P=0.002) and waiting-times over 2 years (P=0.044) as risk factors for early death, while age above 60 (P=0.008) and ischemic aetiology (P=0.029) and pulmonary hypertension (P=0.092) were risk factors for survival. CONCLUSIONS: In times of donor shortage mechanical assistance proves very effective as bridge-to-transplant in patients for whom candidacy follows the standard inclusion procedures. In our settings, a steep increase in LVAD implantation served to salvage patients for whom transplantation became jeopardized due to an ever increasing waiting-time. Circulatory LVAD support could be considered as primary therapy in the future.

Non-Cytotoxic Crosslinkers for Heart Valve Tissue Engineering.

BACKGROUND AND AIM OF THE STUDY: Currently, no effective crosslinking reagents are available to treat xenogenic decellularized heart valve matrices. The study aim was to evaluate the crosslinking effect of quercetin, catechin, caffeic acid and tannic acid on porcine aortic valve matrices. METHODS: Cytotoxicity of the different crosslinkers was evaluated. The mechanical properties of crosslinked porcine matrices and control matrices (non-fixed) were examined by tensile strength testing, as was the cytocompatibility of the fixed matrices. Crosslinked and control matrices were implanted subcutaneously in Wistar rats (n = 9) and, after two weeks, their calcium contents were determined using inductively coupled plasma-mass spectrometry. The antibody reaction against porcine tissue in rat serum was also determined. RESULTS: Cytotoxicity studies showed that crosslinkers, even at high concentrations, did not inhibit cell viability. All crosslinkers except tannic acid improved the mechanical strength of acellular porcine matrices. Moreover, the tensile strength of quercetin-fixed matrices was comparable with that of glutaraldehyde (GTA)-fixed leaflets. Light microscopic evaluation showed that crosslinked matrices caused only a mild lymphocytic inflammatory reaction. Furthermore, quercetin-fixed leaflets exhibited a well-preserved matrix without infiltration of CD3+ cells. After two weeks, calcium levels were 206.33 µg/mg for controls (non-fixed), and 151.33 µg/mg, 181 µg/mg and 163.66 µg/mg for quercetin-, catechin-, and caffeic acid-fixed matrices, respectively. At two weeks after implantation the quercetin-crosslinked matrices also elicited the lowest levels of IgG antibodies. CONCLUSION: The study results identified quercetin as the most suitable crosslinker for heart valve tissue engineering, and a possible alternative to GTA. Further studies are essential to determine whether quercetin crosslinking will allow autologous cell repopulation in order to create a viable heart valve.

Twenty-year single-center experience with the medtronic open pivot mechanical heart valve.

BACKGROUND: Since May 1992 the Medtronic Open Pivot mechanical heart valve has been implanted routinely at the authors' institution. The study aim was to analyze, retrospectively, the 20-year clinical results of the valve. METHODS: Between May 1992 and December 2011 a total of 1,520 valves was inserted into 1,382 consecutive patients (1,012 aortic, 473 mitral, 26 tricuspid, 9 pulmonary). The mean age of the patients was 61±13.2 years. Preoperatively, 65% of the patients were in New York Heart Association (NYHA) class III or greater. Frequent comorbidities included atrial fibrillation (n=419), coronary disease (n=357), and diabetes (n=255). The 99% complete follow-up totaled 10,527 patient-years (range 12 to 244 months). RESULTS: Ninety-day mortality was 5.2% (n=73, 8 valve related). Of the 550 total deaths, 240 were cardiac and 56 valve related. Multivariate analysis selected age, NYHA III or greater, concomitant coronary revascularization, and respiratory insufficiency as risk factors for death. Renal failure was considered a risk factor in the aortic and atrial fibrillation in the mitral subgroup. Erratic international normalized ratio (INR), NYHA class III or greater, and non-sinus rhythm were risk factors for thromboembolism; likewise redo operations in the aortic subgroup. Erratic INR and age were risk factors for bleeding as were over-coagulation and coronary revascularization in the aortic subgroup and redo operations and renal failure in mitral patients. CONCLUSIONS: This 20-year experience demonstrated excellent clinical outcomes with no structural valve failure. Odds ratio defined aortic patients as the lowest risk for adverse events. By contrast atrial fibrillation and elderly age, in combination with instable anticoagulation, yielded the worst long-term results.

Role of myocardial hypertrophy on acute and chronic right ventricular performance in relation to chronic volume overload in a porcine model: relevance for the surgical management of tetralogy of Fallot.

OBJECTIVES: The age for correction of tetralogy of Fallot has progressively declined to the postnatal period, often despite an increased rate of transannular patch repair. However, the long-term effect of premature exposure to chronic pulmonary insufficiency on the right ventricle remains unknown. On the basis of the relationship between the duration of pressure overload and age, the role of previous pressure load-related hypertrophy on right ventricular (RV) performance after chronic volume overload was investigated in a porcine model. METHODS: RV hypertrophy (RVH), induced by pulmonary artery banding, was studied in pigs with (RVH plus pulmonary insufficiency [PI]) and without (RVH) subsequent PI. The effect of volume overload was compared between these 2 groups and pigs without RVH but with PI and controls (sham). Both acute and chronic effects on RV function were studied using conductance technology and validated using echocardiography. RESULTS: After chronic volume overload, the end-systolic and end-diastolic volumes were smaller in the RVH+PI group than in the PI group, including a lower pulmonary regurgitation fraction (25% ± 5% vs 35% ± 5%; P = .002). RVH resulted in better preserved systolic function, confirmed by an increased preload recruitable stroke work slope (14.7 ± 1.8 vs 9.3 ± 1.3 Mw.s/mL; P = .025) and higher RV ejection fraction (51% ± 3% vs 45% ± 4%; P = .05). Myocardial stiffness was impaired in the RVH+PI group versus the PI group (ß, 0.19 ± 0.03 vs 0.12 ± 0.02 mL(-1); P = .001), presenting restrictive physiology only in the condition associating RVH and PI. CONCLUSIONS: The results of the present study have demonstrated that RVH attenuates the RV remodeling process related to chronic PI. It enables better preservation of contractility but at the cost of sustained diastolic impairment. These findings might help to determine the timing and strategy for repair of tetralogy of Fallot when RV outflow tract morphology indicates a definite need for transannular reconstruction.

Reappraisal of a single-centre policy on the contemporary surgical management of active infective endocarditis.

OBJECTIVES: We studied a contemporary cohort of adult patients treated surgically for infective endocarditis (IE) in order to evaluate the surgical approach and predictors of outcomes, in relation to the intercurrent adaptation of the 2006 ACC/AHA guidelines. METHODS: One hundred and eighty-six consecutive patients operated on for active IE from August 1999 to September 2012 were reviewed retrospectively. Clinical presentation, surgical management and outcomes in the two study periods before and after January 2007 were compared (Period 1: n = 95 and Period 2: n = 91). RESULTS: The mean (SD) follow-up was 4.3 (3.8) years and was 99.5% complete. Patients in Period 2 had more frequently associated coronary artery disease (31 vs 18%, P = 0.06), while the microbiology revealed more Staphylococcus species (43 vs 26%, P = 0.02), predominantly Staphylococcus aureus (31 vs 19%; P = 0.07), and less culture-negative cases (7 vs 17%; P = 0.05). The median delay between diagnosis and surgery was 7 days in Period 2 compared with 14 days in Period 1 (P = 0.001). Surgery in Period 2 included more root replacements for aortic valve endocarditis (11 vs 2%; P = 0.02) and mitral valve repairs (18 vs 5%; P = 0.01), while the use of homografts for aortic valve endocarditis was almost abandoned (1 vs 15%; P = 0.001). Hospital mortality was 13% and did not change significantly over both periods (P = 0.66). The independent predictors of hospital mortality were age (P = 0.03), female gender (P = 0.02), previous cardiac surgery (P = 0.02), preoperative serum creatinine level >2 mg/dl (P = 0.05), S. aureus infection (P = 0.02), emergent or salvage operation (P = 0.001) and concomitant coronary artery bypass grafting (P = 0.03). The 1-, 3-, 5- and 10-year survival were 84, 72, 64 and 57%, respectively. Late survival was negatively influenced by S. aureus endocarditis (P < 0.001) and peripheral vascular disease (P = 0.03), whereas associated coronary artery disease (P = 0.07) had a strong impact. CONCLUSIONS: Adaptation of the 2006 ACC/AHA guidelines in the contemporary management of IE led to a shorter interval between diagnosis and surgery. Despite a more extensive and earlier operative approach, IE caused by S. aureus still remains a major determinant of early and late outcomes.

Bioactive porcine matrices in heart valve tissue engineering.

BACKGROUND AND AIM OF THE STUDY: Platelet gel (PG), a storage vehicle of growth factors, can be considered for the application of growth factors in combination with mesenchymal stem cells (MSCs) to accelerate tissue regeneration. Moreover, the addition of bioactive factors to porcine aortic valves could result in a more rapid repopulation. The study aim was to load acellular porcine aortic valve matrices with the PG-rich growth factors and to evaluate the effect on MSC repopulation. METHODS: Ovine mesenchymal stem cells (oMSCs) were isolated from sheep bone marrow. Acellular porcine heart valve matrices (n = 3) were preloaded with heparin and incubated with the PG for 2 h. A quantitative sandwich enzyme immunoassay was used to examine the release of basic fibroblast growth factor (bFGF) and transforming growth factor-beta (TGF-beta) from the matrices, oMSC repopulation was stimulated by static and dynamic culture. RESULTS: The immunoassays revealed that heparin-preloaded PG-incubated matrices showed a sustained release of 56.28 pg/ml bFGF and 30.66 ng/ml TGF-beta1 after 24 h. Dynamic culture induced oMSC invasion in growth factor-loaded matrices. Cell density results showed that dynamic culture significantly enhanced the repopulation of growth factor-loaded matrices (75 +/- 21 cells/mm2) when compared to static culture (26 +/- 10 cells/mm2). CONCLUSION: The incubation of a porcine aortic valve matrix with a PG concentrate creates a bioactive matrix. However, further fine-tuning of the PG concentration is necessary to take full advantage of platelet growth factor interaction between cells and the extracellular matrix in order to optimize cellular repopulation.

Acute and chronic effects of dysfunction of right ventricular outflow tract components on right ventricular performance in a porcine model: implications for primary repair of tetralogy of fallot.

OBJECTIVES: This study investigates the contribution of infundibular versus pulmonary valve (PV) dysfunction on right ventricular (RV) function in a porcine model. BACKGROUND: Clinical outcome after repair of tetralogy of Fallot is determined by the adaptation of the right ventricle to the physiological sequelae of the right ventricular outflow tract (RVOT) reconstruction. Recent surgical techniques are pursuing a PV-versus infundibulum-sparing approach. METHODS: In a porcine model, 3 types of RVOT dysfunction were created and compared with sham-operated controls: infundibular dysfunction (INF), PV insufficiency (PI), and combined infundibular-PV dysfunction (TAP). Both acute and chronic effects on RV function were studied by using conductance technology and magnetic resonance imaging. RESULTS: In animals with PI, pulmonary regurgitant fraction progressed more in the presence of concomitant INF (54% in TAP versus 14% in PI; p = 0.03). Subsequently, RV end-systolic and end-diastolic volume increased more in both groups, resulting in decreased ejection fraction after 3 months. Preload-independent systolic indices showed acute impairment of RV contractility in all treatment groups but most in animals with infundibular scarring (INF and TAP). Further chronic deterioration was observed in animals of the TAP group. RV compliance improved proportionally most in the PI and TAP groups in relation to the extent of RV dilation. CONCLUSIONS: Surgical RVOT dysfunction, whether it includes the infundibulum and/or the PV, has an immediate effect on RV performance. Although impaired RV contractility is due to intrinsic myocardial damage by infundibular distortion, it is chronically furthered by PI-related RV dilation. These findings support the adoption of a RVOT-sparing strategy to treat tetralogy of Fallot.

Twenty years' single-center experience with mechanical heart valves: a critical review of anticoagulation policy.

BACKGROUND AND AIM OF THE STUDY: Since January 1990, a variety of mechanical valves (St. Jude Medical, CarboMedics, ATS Medical) have been implanted routinely at the authors' institution. The study aim was to analyze, retrospectively, the 20-year clinical results of those mechanical valves, and to challenge the anticoagulation policy employed over the years. METHODS: Between January 1990 and December 2008, a total of 2,108 mechanical valves was inserted into 1,887 consecutive patients (1,346 aortic, 725 mitral, 27 tricuspid, 10 pulmonary). The mean age of the patients was 63 +/- 13.2 years, and the majority (61%) were males. Preoperatively, 71% the patients were in NYHA class > or = III (average 3.01). The most frequent comorbidities included: atrial fibrillation (n = 594), coronary disease (n = 567) and diabetes (n = 398). The follow up (99% complete) totaled 13,721 patient-years (pt-yr), and ranged from 12 to 241 months (average 84 months). RESULTS: In-hospital mortality was 5.2% (n = 98, 14 valve-related). Of the 629 late deaths, the majority were cardiac (n = 276). Survival (Kaplan-Meier estimation) was significantly better for aortic valve patients compared to mitral or multiple valve replacement (Mantel-Cox, p < 0.0001). The overall linearized incidences (as %/pt-yr) were: valve thrombosis 0.31, thromboembolism 1.08, and bleeding 0.91. However, as repeated events occurred in several patients, the hazard function was not constant. Multivariate analysis (Cox regression model) showed age > 70 years (p < 0.0001), NYHA class > or = III (p < 0.0001), non-sinus rhythm (p = 0.001), concomitant coronary artery bypass grafting (p = 0.008) and higher International Normalized Ratio (INR) values (p = 0.013) as significant risk factors for death, with a trend for redo operations (p = 0.052). Multivariate analysis found variable INR, non-sinus rhythm and NYHA class > II as significant risk factors for thromboembolism, while long-acting coumadin and NYHA class > II were significant risk factors for bleeding. CONCLUSION: This 20-year experience demonstrated excellent clinical outcomes for patients with mechanical prostheses, with no valve structural failure and an acceptable incidence of adverse events. INR values between 2-2.5 for aortic valve patients, and 3-3.5 for mitral valve patients, yielded the fewest major adverse events.

Left tilt position for easy extracorporeal membrane oxygenation cannula insertion in late pregnancy patients.

The aim was to describe how to avoid technical difficulties during venous femoral cannula insertion for extracorporeal membrane oxygenation (ECMO) in a woman in late pregnancy. A 28-year old pregnant woman presented at 32 weeks of gestation after developing an acute respiratory distress syndrome (ARDS) of an unknown origin that required venovenous ECMO insertion via the femoral vein. A cannula insertion by the Seldinger visual control technique was impossible in the supine position. A left lateral tilt between 15° and 30° was performed by placing a wedge-shaped cushion under the right hip permitting the cannula insertion. We proposed a systematic 15°-30° left lateral tilt position during the ECMO femoral cannula insertion in late pregnancy cases needing ECMO. This precaution should avoid an injury to the vessels due to multiple insertion attempts.

Assessment of a right-ventricular infundibulum-sparing approach in transatrial-transpulmonary repair of tetralogy of Fallot.

OBJECTIVE: The study aimed to evaluate the outcome of transatrial-transpulmonary repair of tetralogy of Fallot in relation to a right-ventricular outflow tract (RVOT)-sparing surgery. METHODS: Based on the surgical management of right-ventricular outflow tract obstruction (RVOTO) at repair of tetralogy of Fallot, 140 children were retrospectively divided into three groups: (1) pulmonary valve (PV)-sparing, (2) infundibulum-sparing and (3) extended trans-annular patch (TAP). Clinical and echocardiographic outcome was assessed with regards to three equally divided study time eras between January 1994 and June 2010. RESULTS: Over a 15-year study period, median age decreased from 11 (2-101) to 5 (1-11) months (p<0.001), whereas type of RVOT repair changed significantly between the first and the last era (group 1: 18-40%, group 2: 25-40% vs group 3: 57-20% (p=0.002)). Mortality was 0%. Complications were mainly related to clinical restrictive RV physiology (27%) and arrhythmia (10%). This cardiac morbidity remained constant over the eras and was associated with younger age (p=0.04), increased postoperative right ventricle/left ventricle (RV/LV) pressure ratio (p=0.01) and type of RVOT repair at the cost of TAP (p=0.03). Median follow-up of 8 years (1-16 years) showed an overall freedom from RVOT re-operation of 84% and 73%, respectively at 5 and 10 years. Most re-operations were for residual/recurrent RVOTO (12%) occurring more frequently in the latter era: 16% versus 7% in era 1 (p=0.08). Late echocardiographic evaluation revealed a strong correlation between severity of pulmonary regurgitation and increased RV/LV size ratio, which was mainly determined by increased TAP length (p<0.001) and duration of follow-up (p=0.06). CONCLUSION: In a 15-year's experience with transatrial-transpulmonary correction of tetralogy of Fallot, a valve- and infundibulum-sparing approach has been advanced by lowering the age for elective repair. This change has been performed without compromising immediate clinical outcome, despite an increased early re-operation rate for residual obstruction. However, longer follow-up will disclose whether this approach is protective against progressive and late RV dysfunction.