Cryopreserved amniotic membrane in chronic nonhealing wounds: a series of case reports.

A case series of the use of amniotic membrane (AM) for treating chronic nonhealing wounds. It presents five cases of polymorbid patients with a total of nine chronic nonhealing wounds. The patient group consisted of four men and one woman with various comorbidities, aged 45-72 years. The mean initial wound size was 15.8 cm2, and the mean time from the onset of the wound to the first application of AM was 122 weeks. The wounds were caused by chronic venous insufficiency and/or peripheral arterial disease. Wounds were treated in a standardized protocol. AM was applied weekly in the first month and then every two weeks. Photo documentation of the wound and microbiological colonization was carried out at each visit. In three out of five patients, the AM treatment effectively promoted healing up to complete wound closure. In two cases, the wounds stayed unhealed despite numerous AM applications. Pain relief was noted in all patients. The success of the treatment was closely tied to patient factors, such as adherence to the prescribed treatment regimen and individual patient characteristics. In some cases, treatment failure was observed, possibly due to underlying comorbidities, wound parameters, or poor patient compliance. AM treatment has the potential to become a viable treatment option for these nonhealing wounds. However, the effectiveness of the treatment may be influenced by various patient factors and the underlying cause of the wound. Therefore, it is crucial to have an individualized treatment plan that considers these particular factors.

Outcome of Application of Cryopreserved Amniotic Membrane Grafts in the Treatment of Chronic Nonhealing Wounds of Different Origins in Polymorbid Patients: A Prospective Multicenter Study.

To compare the therapeutic efficacy of cryopreserved amniotic membrane (AM) grafts and standard of care (SOC) in treating nonhealing wounds (NHW) through a prospective multicenter clinical trial, 42 patients (76% polymorbid) with 54 nonhealing wounds of various etiologies (mainly venous) and an average baseline size of 20 cm2 were included. All patients were treated for at least 6 weeks in the center before they were involved in the study. In the SOC group, 29 patients (36 wounds) were treated. If the wound healed less than 20% of the baseline size after 6 weeks, the patient was transferred to the AM group (35 patients, 43 wounds). Weekly visits included an assessment of the patient's condition, photo documentation, wound debridement, and dressing. Quality of life and the pain degree were subjectively reported by patients. After SOC, 7 wounds were healed completely, 1 defect partially, and 28 defects remained unhealed. AM application led to the complete closure of 24 wounds, partial healing occurred in 10, and 9 remained unhealed. The degree of pain and the quality of life improved significantly in all patients after AM application. This study demonstrates the effectiveness of cryopreserved AM grafts in the healing of NHW of polymorbid patients and associated pain reduction.

The risk profile change in patients with severe chronic thromboembolic pulmonary hypertension treated with subcutaneous treprostinil.

Chronic thromboembolic pulmonary hypertension (CTEPH) is successfully treatable with pulmonary endarterectomy (PEA), balloon pulmonary angioplasty, and medical therapy. Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management risk score (RRS) is able to predict long-term outcome in inoperable patients or in patients with residual PH after surgery. We performed a post hoc analysis of RRS in patients who were enrolled in the CTREPH study (NCT01416636), a randomized, double-blind clinical trial comparing high-dose and low-dose subcutaneous (SC) treprostinil in patients with severe CTEPH that was classified by an interdisciplinary CTEPH team as nonoperable, or as persistent or recurrent pulmonary hypertension after PEA. Baseline mean RRS was similar in both treatment groups (8.7 in high-dose arm vs. 8.6 in low-dose arm), but mean RRS change from baseline to Week 24 was greater in the high-dose treprostinil group than in the low-dose treprostinil group (-0.88 vs. -0.17). The difference in RRS change from baseline to Week 24 between high dose versus low dose was statistically significant with mean difference of -0.70 (95% confidence interval: -1.36 to -0.05, p = 0.0352), and was driven mainly by improvement of World Health Organization functional class and N-terminal pro-brain natriuretic peptide concentration. SC treprostinil therapy administered in standard dose had positive effect on the risk profile measured by RRS in patients with inoperable or persistent/recurrent severe CTEPH. Although our study was limited by the small sample size and post hoc nature, assessment of risk profile is of great importance to this particular patient population with very poor prognosis.

Correction: Jansa et al. Hospitalisation Is Prognostic of Survival in Chronic Thromboembolic Pulmonary Hypertension. J. Clin. Med. 2022, 11, 6189.

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Inter-placental variability is not a major factor affecting the healing efficiency of amniotic membrane when used for treating chronic non-healing wounds.

This study aimed to evaluate the efficacy of cryopreserved amniotic membrane (AM) grafts in chronic wound healing, including the mean percentage of wound closure per one AM application, and to determine whether the healing efficiency differs between AM grafts obtained from different placentas. A retrospective study analyzing inter-placental differences in healing capacity and mean wound closure after the application of 96 AM grafts prepared from nine placentas. Only the placentas from which the AM grafts were applied to patients suffering from long-lasting non-healing wounds successfully healed by AM treatment were included. The data from the rapidly progressing wound-closure phase (p-phase) were analyzed. The mean efficiency for each placenta, expressed as an average of wound area reduction (%) seven days after the AM application (baseline, 100%), was calculated from at least 10 applications. No statistical difference between the nine placentas' efficiency was found in the progressive phase of wound healing. The 7-day average wound reduction in particular placentas varied from 5.70 to 20.99% (median from 1.07 to 17.75) of the baseline. The mean percentage of wound surface reduction of all analyzed defects one week after the application of cryopreserved AM graft was 12.17 ± 20.12% (average ± SD). No significant difference in healing capacity was observed between the nine placentas. The data suggest that if there are intra- and inter-placental differences in AM sheets' healing efficacy, they are overridden by the actual health status of the subject or even the status of its individual wounds.

Central versus Peripheral CTEPH-Clinical and Hemodynamic Specifications.

Background and Objectives: Chronic thromboembolic pulmonary hypertension (CTEPH) is a chronic progressive disease, resulting from persistent arterial obstruction combined with small-vessel remodeling. Central and peripheral CTEPH are distinguished, according to the dominant lesion's location. This is important for surgical or percutaneous interventional assessment or for medical treatment. Material and Methods: Eighty-one patients (51 male/30 female) with confirmed CTEPH were analyzed, while the CENTRAL type included 51 patients (63%) and the PERIPHERAL type 30 patients (37%). Results: A significant difference in CENTRAL type vs. PERIPHERAL type was determined in gender (male 72.5% vs. 46.7%; p = 0.0198). No difference was found in age, functional status, or echocardiographic parameters. Invasive hemodynamic parameters showed a significant difference in mean pulmonary arterial pressure (46 vs. 58 mmHg; p = 0.0002), transpulmonary gradient (34 vs. 47 mmHg; p = 0.0005), and cardiac index (2.04 vs. 2.5 L.min.m2; p = 0.02) but not in pulmonary vascular resistance. Risk factors showed a significant difference only in acute pulmonary embolism (93.8% vs. 60%; p = 0.0002) and malignancy (2% vs. 13.3%; p = 0.0426). Conclusions: Our study showed hemodynamic differences between CENTRAL type vs. PERIPHERAL type CTEPH with a worse hemodynamic picture in CENTRAL form. This may indicate a different pathophysiological response and/or possible additional influences contributing especially to the peripheral pulmonary bed affection.

Hospitalisation Is Prognostic of Survival in Chronic Thromboembolic Pulmonary Hypertension.

This analysis investigated the prognostic value of hospitalisation in chronic thromboembolic pulmonary hypertension (CTEPH) using data from the Czech Republic, wherein pulmonary endarterectomy (PEA) was the only targeted treatment option until 2015. Using a landmark method, this analysis quantified the association between a first CTEPH-related hospitalisation event occurring before 3-, 6-, 9-, and 12-month landmark timepoints and subsequent all-cause mortality in adult CTEPH patients diagnosed between 2003 and 2016 in the Czech Republic. Patients were stratified into operable and inoperable, according to PEA eligibility. CTEPH-related hospitalisations were defined as non-elective. Hospitalisations related to CTEPH diagnosis, PEA, balloon pulmonary angioplasty, or clinical trial participation were excluded. Of 436 patients who survived to ≥3 months post diagnosis, 309 were operable, and 127 were inoperable. Sex- and age-adjusted hazard ratios (HRs) showed CTEPH-related hospitalisation was a statistically significant prognostic indicator of mortality at 3, 9, and 12 months in inoperable patients, with an approximately 2-fold increased risk of death in the hospitalisation group (HRs [95% CI] ranging from 1.98 [1.06-3.70] to 2.17 [1.01-4.63]). There was also a trend of worse survival probabilities in the hospitalisation groups for operable patients, with the difference most pronounced at 3 months, with a 76% increased risk of death (adjusted HR [95% CI] 1.76 [1.15-2.68]). This first analysis on the prognostic value of CTEPH-related hospitalisations demonstrates that a first CTEPH-related hospitalisation is prognostic of mortality in CTEPH, particularly for inoperable patients. These patients may benefit from medical and/or interventional therapy.

Epidemiology of chronic thromboembolic pulmonary hypertension (CTEPH) in the Czech Republic.

This study investigated the epidemiology and survival outcomes of chronic thromboembolic pulmonary hypertension (CTEPH) in the Czech Republic, wherein pulmonary endarterectomy (PEA) surgery was the only targeted treatment option until 2015. This study included all consecutive adults newly diagnosed with CTEPH in the Czech Republic between 2003 and 2016. Incidence/prevalence rates were calculated using general population data extracted from the Institute of Health Information and Statistics of the Czech Republic. Kaplan-Meier estimates of survival from diagnosis until 2018 were calculated. Of a total of 453 patients observed, 236 (52.1%) underwent PEA (median time from diagnosis to PEA: 2.9 months) and 71 (34.1%) had residual pulmonary hypertension (PH) post-PEA. CTEPH incidence rate (95% confidence interval [CI]) between 2006 and 2016 was 4.47 (4.05; 4.91) patients per million (ppm) per year, and the prevalence (95% CI) was 37.43 (33.46; 41.73) ppm in 2016. The rate of CTEPH-related hospitalizations (95% CI) per 100 person-years was 24.4 (22.1; 26.9) for operated patients and 34.2 (30.9; 37.7) for not-operated patients. Median overall survival (95% CI) for all patients from CTEPH diagnosis was 11.2 (9.4; not reached) years. Five-year survival probability (95% CI) was 95.3% (89.9; 97.9) for operated patients without residual PH, 86.3% (75.3; 92.7) for operated patients with residual PH and 61.2% (54.0; 67.6) for not-operated patients. This study reported epidemiological estimates of CTEPH in the Czech Republic consistent with estimates from other national systematic registries; and indicates an unmet medical need in not-operated patients and operated patients with residual PH.

A patient with pulmonary hypertension waiting for donor lungs during the pandemic: 194 days on extracorporeal life support including 143 days on pulmonary artery to left atrium shunt.

Patients with pulmonary hypertension and end-stage lung disease are fraught with high mortality while on a waiting list for lung transplant. With sometimes rapid deterioration they may require veno-arterial extracorporeal membrane oxygenation (VA-ECMO) as an immediate life-saving technique, which is a time-limited solution. The technique of pulmonary artery to left atrium (PA-LA) shunt fitted with an oxygenator enables bridging the patient to transplant for a longer time period. This low-resistance paracorporeal pumpless lung assist device allows for de-adaptation of the right ventricle back to lower afterload before the lung transplantation is carried out. The PA-LA shunt with an oxygenator also conveys a risk of multiple complications with reported median of 10-26 days until transplant. We report a case of pulmonary capillary hemangiomatosis in a 35-year-old female who had to wait for donor lungs during the pandemic of SARS-CoV-2 for 143 days on PA-LA shunt with oxygenator following 51 days on VA-ECMO. The extremely long course associated with multiple complications including three cerebral embolisms, episodes of sepsis and ingrowth of the return cannula into the left ventricular wall gives insight into the limits of this bridging technique.

The healing dynamics of non-healing wounds using cryo-preserved amniotic membrane.

We evaluated the effect of the application of cryo-preserved amniotic membrane on the healing of 26 non-healing wounds (18 patients) with varying aetiologies and baseline sizes (average of 15.4 cm2 ), which had resisted the standard of care treatment for 6 to 456 weeks (average 88.8 weeks). Based on their average general responses to the application of cryo-preserved AM, we could differentiate three wound groups. The first healed group was characterised by complete healing (100% wound closure, maximum treatment period 38 weeks) and represented 62% of treated wounds. The wound area reduction of at least 50% was reached for all wounds in this group within the first 10 weeks of treatment. Exactly 19% of the studied wounds responded partially to the treatment (partially healed group), reaching less than 25% of closure in the first 10 weeks and 90% at maximum for extended treatment period (up to 78 weeks). The remaining 19% of treated wounds did not show any reaction to the AM application (unhealed defects). The three groups have different profiles of wound area reduction, which can be used as a guideline in predicting the healing prognosis of non-healing wounds treated with a cryo-preserved amniotic membrane.

Cell Viability Assessment Using Fluorescence Vital Dyes and Confocal Microscopy in Evaluating Freezing and Thawing Protocols Used in Cryopreservation of Allogeneic Venous Grafts.

The authors present their contribution to the improvement of methods suitable for the detection of the freezing and thawing damage of cells of cryopreserved venous grafts used for lower limb revascularization procedures. They studied the post-thaw viability of cells of the wall of cryopreserved venous grafts (CVG) immediately after thawing and after 24 and 48 h culture at +37 °C in two groups of six CVG selected randomly for slow thawing in the refrigerator and rapid thawing in a water bath at +37 °C. The grafts were collected from multi-organ and tissue brain-dead donors, cryopreserved, and stored in a liquid nitrogen vapor phase for five years. The viability was assessed from tissue slices obtained by perpendicular and longitudinal cuts of the thawed graft samples using in situ staining with fluorescence vital dyes. The mean and median immediate post-thaw viability values above 70% were found in using both thawing protocols and both types of cutting. The statistically significant decline in viability after the 48-h culture was observed only when using the slow thawing protocol and perpendicular cutting. The possible explanation might be the "solution effect damage" during slow thawing, which caused a gentle reduction in the graft cellularity. The possible influence of this phenomenon on the immunogenicity of CVG should be the subject of further investigations.

Surgical repair of a coronary artery aneurysm associated with coronary artery fistula - a case report.

Coronary artery aneurysm is a relatively rare disorder that is usually discovered as a secondary finding in patients undergoing coronary artery angiography. Coronary artery fistulas are relatively more frequent than rare aneurysms and are often associated with other cardiac abnormalities. The etiology of aneurysms is mostly atherosclerotic, and they are less frequently associated with other acquired or congenital diseases, such as Kawasaki disease, connective tissue diseases, septic emboli, arteritis, and iatrogenic disease. We report a 70-year-old woman with a rare combination of a coronary artery aneurysm associated with a coronary artery fistula, which drained into the pulmonary artery. The diagnosis of our patient was made by selective coronary angiography and confirmed by computed tomography angiography. The patient was treated surgically because of the symptomatic course of the disease.

Computed tomography angiographic parameters of pulmonary artery as prognostic factors of residual pulmonary hypertension after pulmonary endarterectomy.

OBJECTIVES: This study aimed to retrospectively assess using computed tomography pulmonary angiography (CTPA) for predicting residual pulmonary hypertension (RPH) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary endarterectomy (PEA). METHODS: We retrospectively analyzed data of 131 patients with CTEPH who underwent PEA in our center (2008-2015). We measured several diameters of the pulmonary artery and thoracic aorta preoperatively. We evaluated the relationship between these measurements (and their indices) and signs of RPH represented by pulmonary artery systolic pressure (PASP) estimated by echocardiography. RESULTS: Significant correlations were observed between the aortopulmonary index and prediction of any residual hypertension and moderate/severe hypertension 1 year after PEA, and any residual hypertension and severe hypertension 2 years after PEA. The aortopulmonary index was significantly related to a reduction in PASP 1 year after the operation. A lower aortopulmonary index (≤0.88 for the ascending aorta and ≤0.64 for the descending aorta) predicted lower RPH. CONCLUSIONS: Preoperative CTPA parameters can be used to assess the risk of RPH after PEA. The aortopulmonary index has significant predictive value for RPH and a reduction in PASP after PEA. Lower values of the aortopulmonary index suggest a better outcome after PEA.

The prevalence and clinical outcome of supraventricular tachycardia in different etiologies of pulmonary hypertension.

PURPOSE: Patients with pulmonary hypertension (PH) frequently suffer from supraventricular tachycardias (SVT). The main purpose of our study was to identify the cumulative incidence of SVT in patients with different etiologies of PH. The secondary objective was to analyse the clinical impact of SVT. METHODS: We retrospectively studied the prevalence of SVT and the clinical outcome in 755 patients (41% males; 60 ± 15 years; mean follow-up 3.8 ± 2.8 years) with PH of different etiologies. The prevalence of SVT was analysed separately in isolated pre-capillary PH (Ipc-PH) and in patients with combined post- and pre-capillary PH (Cpc-PH). RESULTS: The prevalence of SVT in the Ipc-PH group (n = 641) was 25% (n = 162). The most prevalent arrhythmias were atrial fibrillation followed by a typical atrial flutter (17% and 4.4% of all Icp-PH patients). An excessive prevalence of SVT was found in patients with pulmonary arterial hypertension associated with congenital heart disease (35%, p = 0.01). Out of the overall study population, Cpc-PH was present in 114 (15%) patients. Patients with Cpc-PH manifested a higher prevalence of SVT than subjects with Ipc-PH (58; 51% vs. 162; 25%; p <0.0001) and were more likely to have persistent or permanent atrial fibrillation (38; 29% vs. 61; 10%; p <0.0001). Parameters significantly associated with mortality in a multivariate analysis included age, male gender, functional exercise capacity and right atrial diameter (p < 0.05). Neither diagnosis of SVT nor type of arrhythmia predicted mortality. CONCLUSIONS: The study detected a significant prevalence of SVT in the population of PH of different origins. Different spectrum and prevalence of arrhythmia might be expected in different etiologies of PH. Patients with an elevated post-capillary pressure showed a higher arrhythmia prevalence, predominantly due to an excessive number of atrial fibrillations. The diagnosis of SVT was not associated with mortality.

The impact of riociguat on clinical parameters and quality of life in patients with chronic thromboembolic pulmonary hypertension - results of a retrospective clinical registry.

AIMS: The primary objective of the registry was to assess the impact of riociguat on clinical parameters and quality of life in patients with chronic thromboembolic pulmonary hypertension (CTEPH) that was inoperable or persistent/recurrent after pulmonary endarterectomy (PEA). In contrast to randomized pivotal trials, this non-interventional registry evaluated the effectiveness and safety of riociguat in a real-world setting. METHODS: Retrospective data were collected from patients' charts as recorded in routine clinical practice from the initiation of riociguat therapy up to approximately 5 months and 1 year after this initiation. RESULTS: In total, 51 patients from a single site were enrolled. After 5 months (mean duration) of riociguat treatment, the following improvements from baseline were observed: change of distance in the 6-minute walking distance (6MWD) (P=0.066); change of score from the quality of life questionnaire (EQ5D-5L) (P=0.020), and overall self-assessment of health status (P=0.001). New York Heart Association (NYHA) class improved in 24.3% of patients. After 11.2 months (mean duration) of riociguat treatment, the following improvements from baseline were observed: change of distance in the 6MWD test (P=0.006), and overall self-assessment of health status (P=0.009). NYHA class improved in 46.4% of patients. Riociguat was well tolerated. In total, 4 patients reported side effects, with hospitalization required in one case and 2 patients who had to discontinue the treatment. Annual survival rate was 89.1%. CONCLUSION: Riociguat improves functional NYHA class, distance in the 6MWD test and quality of life in a real-world patient population.

Balloon Pulmonary Angioplasty in Patients with Chronic Thromboembolic Pulmonary Hypertension: Impact on Clinical and Hemodynamic Parameters, Quality of Life and Risk Profile.

Balloon pulmonary angioplasty (BPA) is a novel treatment option for patients with chronic thromboembolic pulmonary hypertension (CTEPH) who are not eligible for pulmonary endarterectomy (PEA) or suffer from persistent pulmonary hypertension after PEA. The aim of this study was to evaluate the real-life efficacy and safety of BPA in a consecutive group of patients who were diagnosed and treated in the national referral center for CTEPH in the Czech Republic. Here we report data from 160 BPA procedures performed in 64 patients. Efficacy analysis was performed in the subgroup of 25 patients who completed BPA series. Significant improvements were observed in New York Heart Association functional class (4% to 79% in I/II, p < 0.001), 6 min walking test distance (+54.3 m, p < 0.001), risk profile (15.8% to 68.5% with presence of 2/3 low risk criteria, p < 0.001), pulmonary artery mean pressure (-18%, p < 0.001), pulmonary vascular resistance (-32%, p < 0.001), stroke volume (+17%, p = 0.011) and quality of life (+37% in assessment of overall health status by a patient, p < 0.001). We observed 1 fatal periprocedural complication (1.6% of all 64 patients) and 19 BPA-related non-fatal complications (11.9% of all 160 interventions) that predominantly included hemoptysis (10.0% of all sessions). Overall survival at 12 months was 94.6%.

Lipid Profiling in Epicardial and Subcutaneous Adipose Tissue of Patients with Coronary Artery Disease.

Coronary artery disease is one of the most frequent causes of morbidity and mortality worldwide. It is even more prevalent in patients with type 2 diabetes mellitus who suffer from obesity and increased accumulation of epicardial fat with a possible contributing role in the development of coronary artery disease. We performed an MS-based lipidomic analysis of subcutaneous and epicardial adipose tissue in 23 patients with coronary artery disease stratified for the presence/absence of type 2 diabetes mellitus and a control group of 13 subjects aiming at identification of factors from epicardial fat contributing to the development of coronary artery disease. The samples of adipose tissues were obtained during elective cardiac surgery. They were extracted and analyzed with and without previous triacylglycerols separation by high-pressure liquid chromatography-mass spectrometry (HPLC-MS). Multivariate and univariate analyses were performed. Lipidomics data were correlated with biochemical parameters. We identified multiple changes in monoacylglycerols, diacylglycerols, triacylglycerols, glycerophosphatidylserines, glycerophosphatidylethanolamines, glycerophosphatidylcholines, ceramides, sphingomyelins, and derivatives of cholesterol. Observed changes included molecules with fatty acids with odd (15:0, 15:1, 17:0, 17:1) and even (10:0, 12:0, 14:0, 16:0, 16:1, 18:0, 18:1, 18:2, 20:4, 20:1, 22:0) fatty acids in both types of adipose tissue. More pronounced changes were detected in epicardial adipose tissue compared to subcutaneous adipose tissue of patients with coronary artery disease and type 2 diabetes. Lipidomic analysis of subcutaneous and epicardial adipose tissue revealed different profiles for patients with coronary artery disease and type 2 diabetes, which might be related to coronary artery disease and the presence of type 2 diabetes.

Atrial fibrillation and atrial tachycardia in patients with chronic thromboembolic pulmonary hypertension treated with pulmonary endarterectomy.

Atrial fibrillation (AF) and atrial tachycardia (AT) are frequently observed in patients with chronic thromboembolic pulmonary hypertension (CTEPH) who were treated with pulmonary endarterectomy (PEA). Their prevalence and impact on prognosis of patients are not known. We analysed the prevalence of AF/AT and the clinical outcome in 197 patients with CTEPH treated with PEA (median age 62; interquartile range 53-68 years; 62% males). The prevalence of AF/AT was 29% (57 patients). Compared to patients without arrhythmia, the subjects with AF/AT were older [60 (50-67) vs. 62 (57-70) years], manifested an increased size of the left atrium [39 (35-44) vs. 45 (40-50) mm], had a reduced 6-min walking distance [411 (321-506) vs. 340 (254-460) m], and higher pulmonary artery systolic pressure after PEA [38 (30-47) vs. 45 (38-71) mmHg], all results with P-value <0.05. During the follow-up with a median 4.2 (1.6-6.3) years, 45 (23%) patients died. In a multivariate Cox regression model only the male gender [hazard ratio (HR) 2.27, 95% confidence interval (CI) 1.15-4.50], a reduced 6-min walking distance (HR 3.67, 95% CI 1.74-7.73), and an increased New York Heart Association class (HR 8.56, 95% CI 4.17-17.60) were associated with mortality (P < 0.05). The prevalence of AF/AT in patients with CTEPH treated with PEA is high. Arrhythmias are associated with reduced functional capacity but not with mortality.

Mitral Valve Replacement Using Subvalvular Apparatus: A Systematic Review and Meta-Analysis.

BACKGROUND: To assess clinical outcomes among participants undergoing mitral valve replacement with preservation of subvalvular apparatus. METHODS: Electronic databases, including PubMed, Embase, Science Direct, World of Science, Scopus, Biosis, SciElo and Cochrane library, were probed using an extensive search strategy. Studies that reported at least one clinical outcome, such as morbidity, mortality, early 30-day mortality, myocardial failure, survival, late cerebrovascular events, length of stay, or major operative complications (stroke, prolonged ventilation, and reoperation for bleeding, renal failure, and sternal infection) were considered for inclusion. Data was extracted and pooled into a meta-analysis in RevMan (version 5.3) using a random-effects model. RESULTS: A total of 21 studies with 5,106 participants (age range: 27.3-69.2 years) were included in this meta-analysis. Preservation of the subvalvular apparatus during MVR significantly reduces the risk of long-term mortality (OR: 0.46; 95% CI: 0.33-0.64), but not early mortality (OR: 0.76; 95% CI: 0.12-4.93). No significant difference ejection fraction was observed (SMD: 0.10; 95% CI: -0.44-0.64). Similarly, there was no significant difference in the risk of stroke, renal failure, and pneumonia between C-MVR and in the control group. CONCLUSION: MVR with the preservation of subvalvular apparatus improves clinical outcomes, such as long-term mortality, hospital length of stay, pneumonia, and bleeding. There is no significant difference in the risk of stroke, renal failure, or ICU length of stay. However, there is very limited data available with respect to bleeding, sepsis, and nosocomial infections.