De novo domestication: what about the weeds?

Most high-yielding crops are susceptible to abiotic and biotic stresses, making them particularly vulnerable to the potential effects of climate change. A possible alternative is to accelerate the domestication of wild plants that are already tolerant to harsh conditions and to increase their yields by methods such as gene editing. We foresee that crops' wild progenitors could potentially compete with the resulting de novo domesticated plants, reducing yields. To improve the recognition of weeds, we propose using gene editing techniques to introduce traits into de novo domesticated crops that will allow for visual recognition of the crops by weeding robots that have been trained by machine learning.

Perennials as Future Grain Crops: Opportunities and Challenges.

Perennial grain crops could make a valuable addition to sustainable agriculture, potentially even as an alternative to their annual counterparts. The ability of perennials to grow year after year significantly reduces the number of agricultural inputs required, in terms of both planting and weed control, while reduced tillage improves soil health and on-farm biodiversity. Presently, perennial grain crops are not grown at large scale, mainly due to their early stages of domestication and current low yields. Narrowing the yield gap between perennial and annual grain crops will depend on characterizing differences in their life cycles, resource allocation, and reproductive strategies and understanding the trade-offs between annualism, perennialism, and yield. The genetic and biochemical pathways controlling plant growth, physiology, and senescence should be analyzed in perennial crop plants. This information could then be used to facilitate tailored genetic improvement of selected perennial grain crops to improve agronomic traits and enhance yield, while maintaining the benefits associated with perennialism.

Development of a New Integrated System for Vital Sign Monitoring in Small Animals.

Monitoring the vital signs of mice is an essential practice during imaging procedures to avoid populational losses and improve image quality. For this purpose, a system based on a set of devices (piezoelectric sensor, optical module and thermistor) able to detect the heart rate, respiratory rate, body temperature and arterial blood oxygen saturation (SpO2) in mice anesthetized with sevoflurane was implemented. Results were validated by comparison with the reported literature on similar anesthetics. A new non-invasive electrocardiogram (ECG) module was developed, and its first results reflect the viability of its integration in the system. The sensors were strategically positioned on mice, and the signals were acquired through a custom-made printed circuit board during imaging procedures with a micro-PET (Positron Emission Tomography). For sevoflurane concentration of 1.5%, the average values obtained were: 388 bpm (beats/minute), 124 rpm (respirations/minute) and 88.9% for the heart rate, respiratory rate and SpO2, respectively. From the ECG information, the value obtained for the heart rate was around 352 bpm for injectable anesthesia. The results compare favorably to the ones established in the literature, proving the reliability of the proposed system. The ECG measurements show its potential for mice heart monitoring during imaging acquisitions and thus for integration into the developed system.

Accelerated Domestication of New Crops: Yield is Key.

Sustainable agriculture in the future will depend on crops that are tolerant to biotic and abiotic stresses, require minimal input of water and nutrients and can be cultivated with a minimal carbon footprint. Wild plants that fulfill these requirements abound in nature but are typically low yielding. Thus, replacing current high-yielding crops with less productive but resilient species will require the intractable trade-off of increasing land area under cultivation to produce the same yield. Cultivating more land reduces natural resources, reduces biodiversity and increases our carbon footprint. Sustainable intensification can be achieved by increasing the yield of underutilized or wild plant species that are already resilient, but achieving this goal by conventional breeding programs may be a long-term prospect. De novo domestication of orphan or crop wild relatives using mutagenesis is an alternative and fast approach to achieve resilient crops with high yields. With new precise molecular techniques, it should be possible to reach economically sustainable yields in a much shorter period of time than ever before in the history of agriculture.

High-throughput phenotyping of physiological traits for wheat resilience to high temperature and drought stress.

Interannual and local fluctuations in wheat crop yield are mostly explained by abiotic constraints. Heatwaves and drought, which are among the top stressors, commonly co-occur, and their frequency is increasing with global climate change. High-throughput methods were optimized to phenotype wheat plants under controlled water deficit and high temperature, with the aim to identify phenotypic traits conferring adaptative stress responses. Wheat plants of 10 genotypes were grown in a fully automated plant facility under 25/18 °C day/night for 30 d, and then the temperature was increased for 7 d (38/31 °C day/night) while maintaining half of the plants well irrigated and half at 30% field capacity. Thermal and multispectral images and pot weights were registered twice daily. At the end of the experiment, key metabolites and enzyme activities from carbohydrate and antioxidant metabolism were quantified. Regression machine learning models were successfully established to predict plant biomass using image-extracted parameters. Evapotranspiration traits expressed significant genotype-environment interactions (G×E) when acclimatization to stress was continuously monitored. Consequently, transpiration efficiency was essential to maintain the balance between water-saving strategies and biomass production in wheat under water deficit and high temperature. Stress tolerance included changes in carbohydrate metabolism, particularly in the sucrolytic and glycolytic pathways, and in antioxidant metabolism. The observed genetic differences in sensitivity to high temperature and water deficit can be exploited in breeding programmes to improve wheat resilience to climate change.

Efficient Regulation of CO2 Assimilation Enables Greater Resilience to High Temperature and Drought in Maize.

Increasing temperatures and extended drought episodes are among the major constraints affecting food production. Maize has a relatively high temperature optimum for photosynthesis compared to C3 crops, however, the response of this important C4 crop to the combination of heat and drought stress is poorly understood. Here, we hypothesized that resilience to high temperature combined with water deficit (WD) would require efficient regulation of the photosynthetic traits of maize, including the C4-CO2 concentrating mechanism (CCM). Two genotypes of maize with contrasting levels of drought and heat tolerance, B73 and P0023, were acclimatized at high temperature (38°C versus 25°C) under well-watered (WW) or WD conditions. The photosynthetic performance was evaluated by gas exchange and chlorophyll a fluorescence, and in vitro activities of key enzymes for carboxylation (phosphoenolpyruvate carboxylase), decarboxylation (NADP-malic enzyme), and carbon fixation (Rubisco). Both genotypes successfully acclimatized to the high temperature, although with different mechanisms: while B73 maintained the photosynthetic rates by increasing stomatal conductance (gs), P0023 maintained gs and showed limited transpiration. When WD was experienced in combination with high temperatures, limited transpiration allowed water-savings and acted as a drought stress avoidance mechanism. The photosynthetic efficiency in P0023 was sustained by higher phosphorylated PEPC and electron transport rate (ETR) near vascular tissues, supplying chemical energy for an effective CCM. These results suggest that the key traits for drought and heat tolerance in maize are limited transpiration rate, allied with a synchronized regulation of the carbon assimilation metabolism. These findings can be exploited in future breeding efforts aimed at improving maize resilience to climate change.

Antifungal and Anti-Inflammatory Potential of Bupleurum rigidum subsp. paniculatum (Brot.) H.Wolff Essential Oil.

Fungal infections remain a major health concern with aromatic plants and their metabolites standing out as promising antifungal agents. The present study aims to assess, for the first time, the antifungal and anti-inflammatory potential of Bupleurum subsp. paniculatum (Brot.) H.Wolff essential oil from Portugal. The oil obtained by hydrodistillation and characterized by GC-MS, showed high amounts of monoterpene hydrocarbons, namely α-pinene (29.0-36.0%), ß-pinene (26.1-30.7%) and limonene (10.5-13.5%). The antifungal potential was assessed, according to CLSI guidelines, against several clinical and collection strains. The essential oil showed a broad fungicidal effect being more potent against Cryptococcus neoformans and dermatophytes. Moreover, a significant germ tube inhibition was observed in Candida albicans as well as a disruption of mature biofilms, thus pointing out an effect of the oil against relevant virulent factors. Furthermore, fungal ultrastructural modifications were detected through transmission electron microscopy, highlighting the nefarious effect of the oil. Of relevance, the oil also evidenced anti-inflammatory activity through nitric oxide inhibition in macrophages activated with lipopolysaccharide. In addition, the essential oil's bioactive concentrations did not present toxicity towards macrophages. Overall, the present study confirmed the bioactive potential of B. rigidum subsp. paniculatum essential oil, thus paving the way for the development of effective drugs presenting concomitantly antifungal and anti-inflammatory properties.

Photoprotection and optimization of sucrose usage contribute to faster recovery of photosynthesis after water deficit at high temperatures in wheat.

Plants are increasingly exposed to events of elevated temperature and water deficit, which threaten crop productivity. Understanding the ability to rapidly recover from abiotic stress, restoring carbon assimilation and biomass production, is important to unravel crop climate resilience. This study compared the photosynthetic performance of two Triticum aestivum L. cultivars, Sokoll and Paragon, adapted to the climate of Mexico and UK, respectively, exposed to 1-week water deficit and high temperatures, in isolation or combination. Measurements included photosynthetic assimilation rate, stomatal conductance, in vitro activities of Rubisco (EC 4.1.1.39) and invertase (INV, EC 3.2.1.26), antioxidant capacity and chlorophyll a fluorescence. In both genotypes, under elevated temperatures and water deficit (WD38°C), the photosynthetic limitations were mainly due to stomatal restrictions and to a decrease in the electron transport rate. Chlorophyll a fluorescence parameters clearly indicate differences between the two genotypes in the photoprotection when subjected to WD38°C and showed faster recovery of Paragon after stress relief. The activity of the cytosolic invertase (CytINV) under these stress conditions was strongly related to the fast photosynthesis recovery of Paragon. Taken together, the results suggest that optimal sucrose export/utilization and increased photoprotection of the electron transport machinery are important components to limit yield fluctuations due to water shortage and elevated temperatures.

Single Low Dose of Cocaine-Structural Brain Injury Without Metabolic and Behavioral Changes.

Chronic cocaine use has been shown to lead to neurotoxicity in rodents and humans, being associated with high morbidity and mortality rates. However, recreational use, which may lead to addictive behavior, is often neglected. This occurs, in part, due to the belief that exposure to low doses of cocaine comes with no brain damage risk. Cocaine addicts have shown glucose metabolism changes related to dopamine brain activity and reduced volume of striatal gray matter. This work aims to evaluate the morphological brain changes underlying metabolic and locomotor behavioral outcome, in response to a single low dose of cocaine in a pre-clinical study. In this context, a Balb-c mouse model has been chosen, and animals were injected with a single dose of cocaine (0.5 mg/kg). Control animals were injected with saline. A behavioral test, positron emission tomography (PET) imaging, and anatomopathological studies were conducted with this low dose of cocaine, to study functional, metabolic, and morphological brain changes, respectively. Animals exposed to this cocaine dose showed similar open field activity and brain metabolic activity as compared with controls. However, histological analysis showed alterations in the prefrontal cortex and hippocampus of mice exposed to cocaine. For the first time, it has been demonstrated that a single low dose of cocaine, which can cause no locomotor behavioral and brain metabolic changes, can induce structural damage. These brain changes must always be considered regardless of the dosage used. It is essential to alert the population even against the consumption of low doses of cocaine.

Long-term results after concomitant mitral and aortic valve surgery: repair or replacement?

OBJECTIVES: The reported superiority of mitral valve (MV) repair for isolated MV regurgitation has not been confirmed in mitroaortic valve surgery. Our goals were to evaluate the feasibility of repair in patients undergoing mitral and aortic valve surgery and to identify factors predisposing to MV replacement, to compare long-term outcomes (survival and MV reoperation) of repair and replacement and to perform a subgroup analysis in patients with rheumatic MV disease. METHODS: From January 1992 through December 2016, 1122 consecutive patients were submitted to concomitant aortic and MV surgery in 2 different centres (Coimbra and Santiago). Of these, 837 patients underwent MV repair (74.6%) and 285 patients had MV replacement (25.4%). Rheumatic aetiology was predominant (666 patients; 59.4%). Cumulative follow-up was 9522.6 patient-years (25th-75th percentile 2.6-13.2 years) and was complete for 95.6% of patients. Propensity score matching (1:1) was performed in 232 patients for comparing each treatment option (MV repair and MV replacement). RESULTS: Previous MV intervention, rheumatic aetiology, chronic obstructive pulmonary disease, higher degrees of tricuspid and mitral regurgitation and pulmonary hypertension were independently correlated with MV replacement. The 30-day mortality rate was higher in patients with MV replacement (4.2% vs 1.8%, P = 0.021) and was confirmed in the propensity score matching (4.7% vs 1.7%, P = 0.06). Late survival was lower in the MV replacement group (53.3 ± 4.5% vs 61.7 ± 2.0% at 12 years; P = 0.026) and was confirmed in the propensity score matching (54.6 ± 4.9% vs 63.2 ± 3.8%, P = 0.062) and rheumatic subgroup (57.9 ± 4.8% vs 68.0 ± 2.5%, P = 0.018). Freedom from MV reoperation at 12 years was higher in the MV repair group (94.7 ± 1.1% vs 89.0 ± 3.1%, P = 0.004) but similar in patients with rheumatic MV disease. CONCLUSIONS: MV repair can be performed in most patients undergoing aortic valve replacement. It should be the procedure of choice whenever feasible, because it is associated with lower early and late mortality rates and with freedom from reoperation in non-rheumatic patients.

Primary graft failure after cardiac transplantation: prevalence, prognosis and risk factors.

OBJECTIVES: Primary graft failure (PGF) is a common and devastating complication, despite the advances in perioperative treatment. We aim to evaluate the prevalence of PGF and its impact on survival and to explore associated risk factors. METHODS: From November 2003 through December 2015, 290 patients submitted to cardiac transplantation were classified into non-PGF (243; 84%) and PGF (47; 16%) groups. The characteristics of the recipients were similar regarding age (54.6 ± 10.6 vs 54.0 ± 9.4 years; P = 0.74), male gender (78.2% vs 72.3%; P = 0.38) and transpulmonary gradient (9.4 ± 4.2 vs 10.5 ± 5.6 mmHg; P = 0.15); donors to the PGF group had similar age (35.5 ± 11.4 vs 37.5 ± 10.7 years; P = 0.27) but were predominantly female (21% vs 42.6%; P = 0.002). RESULTS: Mean ischaemic (89.0 ± 36.8 vs 103.3 ± 44.7 min; P = 0.019) and cardiopulmonary bypass (92.8 ± 14.5 vs 126.3 ± 62.4 min; P < 0.001) times were longer in the PGF group. Length of hospital stay was 13.5 ± 7.5 vs 28.9 ± 35.2 days (P= 0.005). Hospital mortality was 4.1% [1.6% for non-PGF and 17% for PGF (P < 0.001)]. Survival at 1, 5 and 10 years was 95.5 ± 1.3% vs 55.3 ± 7.3%, 84.1 ± 2.5% vs 47.4 ± 7.6% and 67.1 ± 3.8% vs 14.4 ± 12%, respectively (P < 0.001). Risk factors for PGF were female donor [odds ratio (OR): 2.56; 95% confidence interval (CI): 1.29-5.09; P = 0.007], total ischaemic time (OR: 1.01; 95% CI: 1.00-1.02; P = 0.032) and preoperative mechanical extracorporeal circulatory support (OR: 11.90; 95% CI: 2.62-54.12; P = 0.001). CONCLUSIONS: Our results demonstrate that PGF is associated with poor outcomes that extend beyond the 1st month and the 1st year after heart transplantation. We found female donor, total ischaemic time and preoperative mechanical extracorporeal circulatory support to be risk factors for PGF.

Long-term follow-up of patients undergoing aortic root enlargement for insertion of a larger prosthesis.

OBJECTIVES: To evaluate the long-term survival of patients undergoing aortic root enlargement (ARE) compared with those with small aortic root (SAR), exploring risk factors for late mortality as well as the influence of patient-prosthesis mismatch (PPM). METHODS: From January 1999 through December 2010, a total of 3724 patients underwent isolated or combined aortic valve replacement at our institution. From these, 239 (6.4%) had transannular ARE with a pericardial patch, to permit implantation of a larger prosthesis. This study population was compared with a control group of 767 patients (20.6%) who were considered to have SAR, as a prosthesis of size 21 or less was implanted. Mean age was comparable: 70.4 ± 12.5 vs 69.9 ± 9.6 years for ARE and SAR groups, respectively (P = 0.552). Female sex predominated in the control group (81.6 vs 88.0%; P = 0.011). Patients of the ARE group tended to have higher mean body surface area (1.59 ± 0.15 vs 1.57 ± 0.13 m(2); P = 0.061) and were less symptomatic (NYHA III-IV: 49.4 vs 57.9%; P = 0.021). RESULTS: Implantation of bioprostheses was more frequent in the ARE group (76.2 vs 52.3%; P < 0.001), while concomitant procedures were more frequent in the SAR group (25.5 vs 32.2%; P = 0.050). Patients in the SAR group had higher moderate PPM (29.7 vs 50.1%; P < 0.001), but no patient was left with severe PPM. Hospital mortality was not statistically different between ARE and SAR groups (0.8 vs 0.5%; P = 0.632). The overall survival rate for ARE group patients at 5, 10 and 15 years was 82.7 ± 2.5, 64.8 ± 3.8 and 36.0 ± 7.5%, respectively, in comparison with 86.2 ± 1.3, 62.9 ± 2.3 and 38.4 ± 4.3% for the SAR group (P = 0.741). There was no significant difference in long-term survival of ARE patients compared with the age- and gender-matched general population (P = 0.794). Long-term survival was not affected by the presence of PPM. Increasing age, male sex, atrial fibrillation, LV end-systolic dimension, preoperative creatinine and NYHA class III-IV were significant predictors of late mortality. CONCLUSIONS: ARE can be done safely, effectively reducing PPM. Although no difference was found in early and late mortality compared with the SAR group, long-term survival rates of ARE patients was comparable with that of the general population, unlike those of the SAR group.

Long-term results of mitral valve surgery for degenerative anterior leaflet or bileaflet prolapse: analysis of negative factors for repair, early and late failures, and survival.

OBJECTIVES: To evaluate the feasibility of mitral valve repair in patients with anterior leaflet (ALP) or bileaflet prolapse (BLP) and identify factors predisposing patients to replacement. To compare long-term survival of patients submitted to repair (Group Repair) against those submitted to replacement (Group Replacement), and investigate causes of early and late failures of repair. METHODS: From January 1992 through December 2012, 768 patients with ALP or BLP were submitted to mitral valve surgery, of whom 501 had degenerative involvement [Myxomatous (Myx)-336 (67.1%) or fibroelastic deficiency (Fed)-165 (32.9%)] and constituted the study population. Isolated ALP was present in 274 patients (54.7%) and BLP in 227 (45.3%). Associated procedures were admitted. RESULTS: Patients with Fed were significantly older (64.4 ± 12.1 vs 54.8 ± 15.5 years, P < 0.001), more symptomatic (63 vs 44.3%; P < 0.001) and with higher incidence of atrial fibrillation (43.6 vs 26.2%; P < 0.001). Repair was achieved in 94.8% of patients with an overall 30-day mortality rate of 1.2% (0.3% in the last decade) and no differences regarding aetiology. Age, moderate to severe left ventricular (LV) dysfunction, previous cardiac surgery, multiple segment prolapse, mitral calcification, leaflet retraction and the performing surgeon were independently associated with replacement. Group Repair patients had a greater adjusted 20-year survival by comparison with Group Replacement (43.4 ± 5.5 vs 13.6 ± 11.3%; P < 0.001) and similar to that of the age- and sex-adjusted general population (P = 0.10). Valve replacement, New York Heart Association (NYHA) class III-IV, pulmonary hypertension and LV dysfunction emerged as independent predictors of late mortality. Patients in NYHA class I-II experienced a higher repair rate (98.4%) and better survival than those in Class III-IV. Two repair patients were reoperated during the first year after surgery (early failure) and both were 'rerepaired'. Late failure was observed in 21 patients, mostly for progression of the disease. The 20-year rate of freedom from reoperation was 88 ± 2.7%, significantly worse in ALP patients (P = 0.040), and not different between Fed and Myx. CONCLUSIONS: Patients with ALP or BLP can be submitted to surgery with low mortality and great probability of repair in expert hands. Patients should be operated on at an early phase (asymptomatic or mildly symptomatic), because there is a higher probability of repair and greater benefit on long-term survival.

Mitral valve surgery after percutaneous mitral commissurotomy: is repair still feasible?

OBJECTIVES: Due to progression of rheumatic disease, percutaneous mitral commissurotomy (PMC) is a palliative procedure. We aimed at evaluating the outcomes of patients requiring surgery for failure of PMC, focusing on the fate of the mitral valve (MV) (repair versus replacement). METHODS: From January 1993 through December 2012, 61 patients with previous PMC were submitted to MV surgery. Detailed operative findings were collected from all patients and an intraoperative anatomical score was introduced to predict reparability. Time to surgery, overall survival and freedom from reoperation were analysed. RESULTS: The mean time to surgery after PMC was 6.9±5.9 years and indications were restenosis in 25 patients (41%) and mitral regurgitation or mixed lesion in 36 (59%). Nine patients (14.8%) had more than one previous intervention. Intraoperative inspection of the valve revealed leaflet laceration outside the commissural area in 27 patients (44.3%). Valve repair was accomplished in 38 patients (62.3%). Pulmonary hypertension, calcification and intraoperative anatomical score were independently associated with the probability of valve replacement (OR 1.12, OR 7.03 and OR 4.49, respectively, P<0.05). There was no hospital mortality. MV area increased on average 1.6 cm2 after surgery to 2.7 cm2; 5-, 10- and 20-year survival rates were 98.1±1.9, 91±5.2 and 82.7±9.2%, respectively. The rate of freedom from mitral reoperation (for repaired cases) at 5, 10 and 15 years was 100, 95.8±4.1 and 87.8±8.5%, respectively. There was no difference in survival between repaired or replaced MVs, but the former had less valve-related events during follow-up. CONCLUSION: The MV can be repaired after failed PMC, with very low complication rates and excellent long-term results. Hence, whenever possible, these patients should be sent to reference centres where repair can be successfully achieved.

Negative impact of atrial fibrillation and pulmonary hypertension after mitral valve surgery in asymptomatic patients with severe mitral regurgitation: a 20-year follow-up.

OBJECTIVES: The timing for mitral valve (MV) surgery in asymptomatic patients with severe mitral regurgitation (MR) and preserved left ventricular (LV) function remains controversial. We aimed at analysing the long-term outcome of asymptomatic patients with atrial fibrillation (AF) and/or pulmonary hypertension (PHT) after successful MV repair. METHODS: From January 1992 to December 2012, 382 patients with severe degenerative MR, with no or mild symptoms, preserved LV function (ejection fraction > 60%) and LV systolic dimensions <45 mm were submitted to surgery and followed up for up to 22 years (3209 patient-years). Patients with associated surgeries, other than tricuspid repair, were excluded. Patients with AF and/or PHT (Group A; n = 106, 24.4%) were compared with patients without these comorbidities (Group B; n = 276, 63.6%). Propensity-score matching (for preoperative variables) was performed obtaining 102 patients in each arm. Survival and event-free survival [major cardiac and cerebrovascular events (MACCEs); freedom from mitral reoperation and recurrent moderate and severe MR] were analysed. RESULTS: MV repair was performed in 98.2% of cases and tricuspid annuloplasty in 6.9%. Overall 30-day mortality was 0.8%, not different between groups, and absent in patients with isolated posterior leaflet prolapse (n = 211). Patients with AF/PHT had worse late survival by comparison with Group B patients (67.0 ± 7.4 vs 86.5 ± 3.9% at 15 years, P < 0.001), survival free from MACCE (52.7 ± 8.7 vs 74.5 ± 5.0%, P < 0.001), from recurrent moderate and severe MR (65.1 ± 10.3 vs 87.0 ± 3.8%, P = 0.002) and from mitral reoperation during the follow-up (87.3 ± 6.3 vs 94.2 ± 2.7%, P = 0.04). These differences were confirmed in the propensity score-matched population. Patients from Group A also displayed a lesser degree of reverse remodelling. There was a significant reduction in the systolic pulmonary artery pressure (SPAP) after surgery, more pronounced in Group A patients; nonetheless, the mean SPAP at late follow-up was higher in these patients (45 vs 30 mmHg). CONCLUSIONS: MV repair can be achieved in the great majority of patients with degenerative regurgitation, with low mortality (<1%). Asymptomatic or mildly symptomatic patients with severe MR, preserved LV function and AF/PHT had poorer long-term survival and event-free survival even after a successful surgery. The durability of MV repair was also compromised in these patients, which indicates that they should have been operated earlier.

Surgical Treatment of Posterior Mitral Valve Prolapse: Towards 100% Repair.

BACKGROUND: The study aim was to evaluate the immediate and long-term results of surgical treatment of isolated posterior mitral valve leaflet prolapse (PLP), focusing on survival and freedom from recurrent mitral regurgitation (MR). METHODS: Between January 1998 and December 2012, a total of 492 consecutive patients (375 males, 117 females; mean age 61.8 ± 12.1 years; range: 13-86 years) with isolated PLP [304 (61.8%) with myxomatous degeneration; 188 (38.2%) with fibroelastic deficiency] were treated at the authors' institution. Of these patients, 202 (41.1%) were in NYHA class III-IV, and atrial fibrillation was present in 104 (21.1%). Mitral valve repair was achieved in 484 patients (98.4%), resection was performed in 419 (85.2%), and prosthetic ring annuloplasty was used in 436 (88.6%). Concomitant procedures were performed in 153 patients (31.1%), including tricuspid valve repair in 50 (10.2%), aortic valve surgery in 34 (6.9%), and coronary artery bypass grafting (CABG) in 64 (13%). RESULTS: The hospital mortality rate was 0.2%, and the mean follow up was 7.1 ± 3.9 years. There were 71 late deaths (14.4%), and overall survival at five, 10 and 15 years was 91.7 ± 1.3%, 82.1 ± 2.3% and 64.7 ± 6.1%, respectively. There was no significant difference in long-term survival compared with the age- and gender-matched general population (p = 0.146). Multivariate Cox-proportional hazard analysis showed older age (HR 1.03 per annum), left ventricular dysfunction (HR 2.44), atrial fibrillation (HR 1.96), left ventricular end-diastolic dimension (HR 1.05 per mm) and non-use of prosthetic ring (HR 3.03) as significant predictors of late mortality. Recurrence of moderate or severe MR occurred in 31 patients, six of whom underwent mitral valve reoperation. Predictors of late recurrence of MR were fibroelastic deficiency (HR 2.38), mitral calcification (HR 5.26), posterior leaflet plication (HR 3.58), absence of complete ring annuloplasty (HR 3.84) and systolic pulmonary artery pressure at discharge (HR 1.10 per mmHg). Freedom from mitral valve reoperation at 15 years was 97.4 ± 1.1% CONCLUSIONS: Mitral valve repair in isolated PLP can be achieved in virtually all cases with a very low operative risk and a high durability of repair. Atrial fibrillation or large left ventricles are associated with a poor prognosis. Failure to use a complete ring annuloplasty carries a risk not only for the return of MR but also for survival.

Long-term follow-up of asymptomatic or mildly symptomatic patients with severe degenerative mitral regurgitation and preserved left ventricular function.

OBJECTIVES: The timing for mitral valve surgery in asymptomatic patients with severe mitral regurgitation and preserved left ventricular function remains controversial. We analyzed the immediate and long-term outcomes of these patients after surgery. METHODS: From January 1992 to December 2012, 382 consecutive patients with severe chronic degenerative mitral regurgitation, with no or mild symptoms, and preserved left ventricular function (ejection fraction ≥ 60%) were submitted to surgery and followed for up to 22 years (3209 patient-years). Patients with associated surgeries, other than tricuspid valve repair, were excluded. Cox proportional-hazard survival analysis was performed to determine predictors of late mortality and mitral reoperation. Subgroup analysis involved patients with atrial fibrillation or pulmonary hypertension. RESULTS: Mitral valvuloplasty was performed in 98.2% of cases. Thirty-day mortality was 0.8%. Overall survival at 5, 10, and 20 years was 96.3% ± 1.0%, 89.7% ± 2.0%, and 72.4% ± 5.8%, respectively, and similar to the expected age- and gender-adjusted general population. Patients with atrial fibrillation/pulmonary hypertension had a 2-fold risk of late mortality compared with the remaining patients (hazard ratio, 2.54; 95% confidence interval, 1.17-4.80; P = .018). Benefit was age-dependent only in younger patients (<65 years; P = .016). Patients with atrial fibrillation/pulmonary hypertension (hazard ratio, 4.20, confidence interval, 1.10-11.20; P = .037) and patients with chordal shortening were at increased risk for reoperation, whereas patients with P2 prolapse (hazard ratio, 0.06; confidence interval, 0.008-0.51; P = .037) and patients with myxomatous valves (hazard ratio, 0.072; confidence interval, 0.008-0.624; P = .017) were at decreased risk. CONCLUSIONS: Mitral valve repair can be achieved in the majority of patients with low mortality (<1%) and excellent long-term survival. Patients with atrial fibrillation/pulmonary hypertension had compromised long-term survival, particularly younger patients (aged <65 years), and are at increased risk of mitral reoperation.

Concomitant aortic and mitral surgery: to replace or repair the mitral valve?

OBJECTIVES: The study objectives were to evaluate the perioperative outcomes of concomitant mitral and aortic valve surgery and to determine the influence of mitral valve repair versus replacement on survival and adverse events. METHODS: The study population comprised 261 patients with a mean age of 61.3±11.2 (19-82) years; 57.5% were male, and 73% were in New York Heart Association class III or IV. Mitral valve repair was performed in 209 patients (80%), and mitral valve replacement was performed in 52 patients (20%). Follow-up was complete for 95% of the patients (1395 patient-years). We specifically examined the impact of mitral valve repair versus replacement by comparing 2 propensity-matched subgroups. RESULTS: Degenerative and functional mitral regurgitation, and left ventricular dilation and dysfunction were associated with mitral valve repair (P<.05). Rheumatic disease, chronic obstructive pulmonary disease, redo surgery, mitral calcification, and atrial fibrillation were more frequently related to mitral valve replacement (P<.05). Overall 30-day mortality was 1.1% (3 patients). Overall 1-, 5-, and 8-year survival were 98.0%±2.0%, 85.9%±6.1%, and 79.8%±8.2%, respectively, for the mitral valve replacement group and 95.3%±1.5%, 87.4%±2.6%, and 75.2%±4.0%, respectively, for the mitral valve repair group (P=.906). This was confirmed by comparable survival in propensity-matched analyses. Mitral valve repair showed a survival advantage in older patients (aged ≥65 years) and patients with nonrheumatic mitral valves (P=.017 and P=.034, respectively). Bleeding events (83% vs 60%), endocarditis (97.6% vs 84.6%), and reoperation (97.6% vs 86.9%) were higher in those undergoing mitral valve replacement. Freedom from major adverse valve-related events was higher for the mitral valve repair group (P=.002). Mitral valve replacement was identified as an independent risk factor for major adverse valve-related events (hazard ratio, 1.99; P=.018). CONCLUSIONS: Concomitant mitral and aortic valve surgery carries a low surgical risk. The choice of the mitral procedure did not significantly affect survival. However, mitral valve replacement was associated with an increased incidence of adverse events. Thus, valve repair, whenever feasible, is a better option.