Oral Use of Phenytoin to Reduce Calcification in Bovine Pericardium and Porcine Aortic Leaflets Implants in Rats.

INTRODUCTION: This study aims to test the effect of phenytoin as an inhibitor of the process of dystrophic calcification in bovine pericardium and porcine leaflets implanted in the subcutaneous tissue of rats. METHODS: Isolated segments of biomaterials were implanted subcutaneously in young rats. The study groups received 500 mg phenytoin per kilogram of diet per day. After 90 days, samples were collected and quantitative calcification assessment by optical microscopy, radiological studies with mammography, and atomic emission spectrometry were performed. RESULTS: Inflammatory reaction was a frequent finding in all groups when analyzed by optical microscopy. The calcium level assessed by atomic absorption spectrophotometry was significantly lower in the study groups using phenytoin compared to the control groups (control bovine pericardium group X=0.254±0.280 µg/mg; study bovine pericardium group X=0.063±0.025 µg/mg; control porcine aortic leaflets group X=0.640±0.226 µg/mg; study porcine aortic leaflets group X=0.056±0.021 µg/mg; P<0.05). Radiologic studies revealed a statistically significant difference between the groups treated with and without phenytoin (not only regarding the bovine pericardium but also the porcine leaflets). CONCLUSION: The results obtained suggest that phenytoin reduces the calcification process of bovine pericardium segments and porcine aortic leaflets in subdermal implants in rats; also, the incidence of calcification in bovine pericardium grafts was similar to that of porcine aortic leaflets.

Oral Use of Phenytoin to Reduce Calcification in Bovine Pericardium and Porcine Aortic Leaflets Implants in Rats

Abstract Introduction: This study aims to test the effect of phenytoin as an inhibitor of the process of dystrophic calcification in bovine pericardium and porcine leaflets implanted in the subcutaneous tissue of rats. Methods: Isolated segments of biomaterials were implanted subcutaneously in young rats. The study groups received 500 mg phenytoin per kilogram of diet per day. After 90 days, samples were collected and quantitative calcification assessment by optical microscopy, radiological studies with mammography, and atomic emission spectrometry were performed. Results: Inflammatory reaction was a frequent finding in all groups when analyzed by optical microscopy. The calcium level assessed by atomic absorption spectrophotometry was significantly lower in the study groups using phenytoin compared to the control groups (control bovine pericardium group X=0.254±0.280 µg/mg; study bovine pericardium group X=0.063±0.025 µg/mg; control porcine aortic leaflets group X=0.640±0.226 µg/mg; study porcine aortic leaflets group X=0.056±0.021 µg/mg; P<0.05). Radiologic studies revealed a statistically significant difference between the groups treated with and without phenytoin (not only regarding the bovine pericardium but also the porcine leaflets). Conclusion: The results obtained suggest that phenytoin reduces the calcification process of bovine pericardium segments and porcine aortic leaflets in subdermal implants in rats; also, the incidence of calcification in bovine pericardium grafts was similar to that of porcine aortic leaflets.

Coronary Artery Bypass Graft Surgery Improves Survival Without Increasing the Risk of Stroke in Patients with Ischemic Heart Failure in Comparison to Percutaneous Coronary Intervention: A Meta-Analysis With 54,173 Patients.

OBJECTIVE: To evaluate whether there is any difference on the results of patients treated with coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) in the setting of ischemic heart failure (HF). METHODS: Databases (MEDLINE, Embase, Cochrane Controlled Trials Register [CENTRAL/CCTR], ClinicalTrials.gov, Scientific Electronic Library Online [SciELO], Literatura Latino-americana e do Caribe em Ciências da Saúde [LILACS], and Google Scholar) were searched for studies published until February 2019. Main outcomes of interest were mortality, myocardial infarction, repeat revascularization, and stroke. RESULTS: The search yielded 5,775 studies for inclusion. Of these, 20 articles were analyzed, and their data were extracted. The total number of patients included was 54,173, and those underwent CABG (N=29,075) or PCI (N=25098). The hazard ratios (HRs) for mortality (HR 0.763; 95% confidence interval [CI] 0.678-0.859; P<0.001), myocardial infarction (HR 0.481; 95% CI 0.365-0.633; P<0.001), and repeat revascularization (HR 0.321; 95% CI 0.241-0.428; P<0.001) were lower in the CABG group than in the PCI group. The HR for stroke showed no statistically significant difference between the groups (random effect model: HR 0.879; 95% CI 0.625-1.237; P=0.459). CONCLUSION: This meta-analysis found that CABG surgery remains the best option for patients with ischemic HF, without increase in the risk of stroke.

Coronary artery bypass graft surgery improves survival without increasing the risk of stroke in patients with ischemic heart failure in comparison to percutaneous coronary intervention: a meta-analysis with 54, 173 patients

Abstract Objective: To evaluate whether there is any difference on the results of patients treated with coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) in the setting of ischemic heart failure (HF). Methods: Databases (MEDLINE, Embase, Cochrane Controlled Trials Register [CENTRAL/CCTR], ClinicalTrials.gov, Scientific Electronic Library Online [SciELO], Literatura Latino-americana e do Caribe em Ciências da Saúde [LILACS], and Google Scholar) were searched for studies published until February 2019. Main outcomes of interest were mortality, myocardial infarction, repeat revascularization, and stroke. Results: The search yielded 5,775 studies for inclusion. Of these, 20 articles were analyzed, and their data were extracted. The total number of patients included was 54,173, and those underwent CABG (N=29,075) or PCI (N=25098). The hazard ratios (HRs) for mortality (HR 0.763; 95% confidence interval [CI] 0.678-0.859; P<0.001), myocardial infarction (HR 0.481; 95% CI 0.365-0.633; P<0.001), and repeat revascularization (HR 0.321; 95% CI 0.241-0.428; P<0.001) were lower in the CABG group than in the PCI group. The HR for stroke showed no statistically significant difference between the groups (random effect model: HR 0.879; 95% CI 0.625-1.237; P=0.459). Conclusion: This meta-analysis found that CABG surgery remains the best option for patients with ischemic HF, without increase in the risk of stroke.

Impact of Prosthesis-Patient Mismatch on 1-Year Outcomes after Transcatheter Aortic Valve Implantation: Meta-analysis of 71,106 Patients.

OBJECTIVES: This study sought to evaluate the impact of prosthesis-patient mismatch (PPM) on the risk of early-term mortality after transcatheter aortic valve implantation (TAVI). METHODS: Databases (Medical Literature Analysis and Retrieval System Online [MEDLINE], Excerpta Medica dataBASE [EMBASE], Cochrane Controlled Trials Register [CENTRAL/CCTR], ClinicalTrials.gov, Scientific Electronic Library Online [SciELO], Latin American and Caribbean Literature on Health Sciences [LILACS], and Google Scholar) were searched for studies published until February 2019. PPM after TAVI was defined as moderate if the indexed effective orifice area (iEOA) was between 0.85 cm2/m2 and 0.65 cm2/m2 and as severe if iEOA ≤ 0.65 cm2/m2. RESULTS: The search yielded 1,092 studies for inclusion. Of these, 18 articles were analyzed, and their data extracted. The total number of patients included who underwent TAVI was 71,106. The incidence of PPM after TAVI was 36.3% (25,846 with PPM and 45,260 without PPM). One-year mortality was not increased in patients with any PPM (odds ratio [OR] 1.021, 95% confidence interval [CI] 0.979-1.065, P=0.338) neither in those with moderate PPM (OR 0.980, 95% CI 0.933-1.029, P=0.423). Severe PPM was separately associated with high risk (OR 1.109, 95% CI 1.041-1.181, P=0.001). CONCLUSION: The presence of severe PPM after TAVI increased early-term mortality. Although moderate PPM seemed harmless, the findings of this study cannot not rule out the possibility of it being detrimental, since there are other registries that did not address this issue yet.

Prosthesis-Patient Mismatch after Surgical Aortic Valve Replacement: Neither Uncommon nor Harmless.

Prosthesis-patient mismatch (PPM) after surgical aortic valve replacement (SAVR) is an issue that has been overlooked (not to say neglected). Cardiac surgeons must bear in mind that this is a real problem that we must tackle. The purpose of this paper is to be a wake-up call to the surgical community by giving a brief overview of what PPM is, its incidence and impact on the outcomes. We also discuss the increasing role played by imaging for predicting and assessing PPM after SAVR (with which surgeons must become more acquainted) and, finally, we present some options to avoid PPM after the surgical procedure.

Prosthesis-patient mismatch after surgical aortic valve replacement: neither uncommon nor harmless

Abstract Prosthesis-patient mismatch (PPM) after surgical aortic valve replacement (SAVR) is an issue that has been overlooked (not to say neglected). Cardiac surgeons must bear in mind that this is a real problem that we must tackle. The purpose of this paper is to be a wake-up call to the surgical community by giving a brief overview of what PPM is, its incidence and impact on the outcomes. We also discuss the increasing role played by imaging for predicting and assessing PPM after SAVR (with which surgeons must become more acquainted) and, finally, we present some options to avoid PPM after the surgical procedure.

Impact of prosthesis-patient mismatch on 1-year outcomes after transcatheter aortic valve implantation: meta-analysis of 71, 106 patients

Abstract Objectives: This study sought to evaluate the impact of prosthesis-patient mismatch (PPM) on the risk of early-term mortality after transcatheter aortic valve implantation (TAVI). Methods: Databases (Medical Literature Analysis and Retrieval System Online [MEDLINE], Excerpta Medica dataBASE [EMBASE], Cochrane Controlled Trials Register [CENTRAL/CCTR], ClinicalTrials.gov, Scientific Electronic Library Online [SciELO], Latin American and Caribbean Literature on Health Sciences [LILACS], and Google Scholar) were searched for studies published until February 2019. PPM after TAVI was defined as moderate if the indexed effective orifice area (iEOA) was between 0.85 cm2/m2 and 0.65 cm2/m2 and as severe if iEOA ≤ 0.65 cm2/m2. Results: The search yielded 1,092 studies for inclusion. Of these, 18 articles were analyzed, and their data extracted. The total number of patients included who underwent TAVI was 71,106. The incidence of PPM after TAVI was 36.3% (25,846 with PPM and 45,260 without PPM). One-year mortality was not increased in patients with any PPM (odds ratio [OR] 1.021, 95% confidence interval [CI] 0.979-1.065, P=0.338) neither in those with moderate PPM (OR 0.980, 95% CI 0.933-1.029, P=0.423). Severe PPM was separately associated with high risk (OR 1.109, 95% CI 1.041-1.181, P=0.001). Conclusion: The presence of severe PPM after TAVI increased early-term mortality. Although moderate PPM seemed harmless, the findings of this study cannot not rule out the possibility of it being detrimental, since there are other registries that did not address this issue yet.

Prosthesis-patient mismatch negatively affects outcomes after mitral valve replacement: meta-analysis of 10, 239 patients

Abstract Objective: This study sought to evaluate the impact of prosthesis-patient mismatch on the risk of perioperative and long-term mortality after mitral valve replacement. Methods: Databases were researched for studies published until December 2018. Main outcomes of interest were perioperative and 10-year mortality and echocardiographic parameters. Results: The research yielded 2,985 studies for inclusion. Of these, 16 articles were analyzed, and their data extracted. The total number of patients included was 10,239, who underwent mitral valve replacement. The incidence of prosthesis-patient mismatch after mitral valve replacement was 53.7% (5,499 with prosthesis-patient mismatch and 4,740 without prosthesis-patient mismatch). Perioperative (OR 1.519; 95%CI 1.194-1.931, P<0.001) and 10-year (OR 1.515; 95%CI 1.280-1.795, P<0.001) mortality was increased in patients with prosthesis-patient mismatch. Patients with prosthesis-patient mismatch after mitral valve replacement had higher systolic pulmonary artery pressure and transprosthethic gradient and lower indexed effective orifice area and left ventricle ejection fraction. Conclusion: Prosthesis-patient mismatch increases perioperative and long-term mortality. Prosthesis-patient mismatch is also associated with pulmonary hypertension and depressed left ventricle systolic function. The findings of this study support the implementation of surgical strategies to prevent prosthesis-patient mismatch in order to decrease mortality rates.

Prosthesis-Patient Mismatch Negatively Affects Outcomes after Mitral Valve Replacement: Meta-Analysis of 10,239 Patients.

OBJECTIVE: This study sought to evaluate the impact of prosthesis-patient mismatch on the risk of perioperative and long-term mortality after mitral valve replacement. METHODS: Databases were researched for studies published until December 2018. Main outcomes of interest were perioperative and 10-year mortality and echocardiographic parameters. RESULTS: The research yielded 2,985 studies for inclusion. Of these, 16 articles were analyzed, and their data extracted. The total number of patients included was 10,239, who underwent mitral valve replacement. The incidence of prosthesis-patient mismatch after mitral valve replacement was 53.7% (5,499 with prosthesis-patient mismatch and 4,740 without prosthesis-patient mismatch). Perioperative (OR 1.519; 95%CI 1.194-1.931, P<0.001) and 10-year (OR 1.515; 95%CI 1.280-1.795, P<0.001) mortality was increased in patients with prosthesis-patient mismatch. Patients with prosthesis-patient mismatch after mitral valve replacement had higher systolic pulmonary artery pressure and transprosthethic gradient and lower indexed effective orifice area and left ventricle ejection fraction. CONCLUSION: Prosthesis-patient mismatch increases perioperative and long-term mortality. Prosthesis-patient mismatch is also associated with pulmonary hypertension and depressed left ventricle systolic function. The findings of this study support the implementation of surgical strategies to prevent prosthesis-patient mismatch in order to decrease mortality rates.

Current Practice of State-of-the-Art Coronary Revascularization in Patients with Heart Failure.

The best treatment for patients with ischemic heart failure (HF) is still on debate. There is growing evidence that coronary artery bypass graft (CABG) benefits these patients. The current recommendations for revascularization in this context are that CABG is reasonable when it comes to decreasing morbidity and mortality rates for patients with severe left ventricular dysfunction (ejection fraction <35%), and significant coronary artery disease (CAD) and should be considered in patients with operable coronary anatomy, regardless whether or not there is a viable myocardium (class IIb). Percutaneous coronary intervention (PCI) does not have enough data to allow the panels to reach a conclusion. The Korean Acute Heart Failure registry (KorAHF) had its data released recently, showing that patients with acute HF who underwent CABG had lower death rates, more complete revascularization and less adverse outcomes compared with patients treated with PCI. Recent ESC/EACTS guidelines on myocardial revascularization clearly recommended CABG as the first choice of revascularization strategy in patients with multivessel disease and acceptable surgical risk to improve prognosis in this scenario of left ventricular dysfunction. However, a high peri-procedural risk must be compared with the benefit of late mortality, and pros and cons of each strategy (either PCI or CABG) must be weighed in the decision-making process. Spurred on by the publication of the above-mentioned article and the release of new guidelines, we went on to write an overview of the current practice of state-of-the-art coronary revascularization options in patients with HF.

Current practice of state-of-the-art coronary revascularization in patients with heart failure

Abstract The best treatment for patients with ischemic heart failure (HF) is still on debate. There is growing evidence that coronary artery bypass graft (CABG) benefits these patients. The current recommendations for revascularization in this context are that CABG is reasonable when it comes to decreasing morbidity and mortality rates for patients with severe left ventricular dysfunction (ejection fraction <35%), and significant coronary artery disease (CAD) and should be considered in patients with operable coronary anatomy, regardless whether or not there is a viable myocardium (class IIb). Percutaneous coronary intervention (PCI) does not have enough data to allow the panels to reach a conclusion. The Korean Acute Heart Failure registry (KorAHF) had its data released recently, showing that patients with acute HF who underwent CABG had lower death rates, more complete revascularization and less adverse outcomes compared with patients treated with PCI. Recent ESC/EACTS guidelines on myocardial revascularization clearly recommended CABG as the first choice of revascularization strategy in patients with multivessel disease and acceptable surgical risk to improve prognosis in this scenario of left ventricular dysfunction. However, a high peri-procedural risk must be compared with the benefit of late mortality, and pros and cons of each strategy (either PCI or CABG) must be weighed in the decision-making process. Spurred on by the publication of the above-mentioned article and the release of new guidelines, we went on to write an overview of the current practice of state-of-the-art coronary revascularization options in patients with HF.

Impact of surgical aortic root enlargement on the outcomes of aortic valve replacement: a meta-analysis of 13 174 patients.

OBJECTIVES: This study sought to evaluate the impact of surgical aortic root enlargement (ARE) on the perioperative outcomes of aortic valve replacement (AVR). METHODS: Databases were searched for studies published until April 2018 to carry out a systematic review followed by meta-analysis of results. RESULTS: The search yielded 1468 studies for inclusion. Of these, 10 articles were analysed and their data extracted. A total of 13 174 patients (AVR with ARE: 2819 patients; AVR without ARE: 10 355 patients) were included from studies published from 2002 to 2018. The total rate of ARE was 21.4%, varying in the studies from 5.7% to 26.3%. The overall odds ratio (OR) [95% confidence interval (CI)] for perioperative mortality showed a statistically significant difference between the groups (among 10 studies), with a higher risk in the 'AVR with ARE' group (OR 1.506, 95% CI 1.209-1.875; P < 0.001), but not when adjusted for isolated AVR + ARE without any concomitant procedures such as mitral valve surgery, coronary artery bypass surgery, etc. (OR 1.625, 95% CI 0.968-2.726; P = 0.066-among 6 studies). The 'AVR with ARE' group showed an overall lower risk of significant patient-prosthesis mismatch among 9 studies (OR 0.472, 95% CI 0.295-0.756; P = 0.002) and a higher overall difference in means of indexed effective orifice area among 10 studies (random-effect model: 0.06 cm2/m2, 95% CI 0.029-0.103; P < 0.001). CONCLUSIONS: Surgical ARE seems to be associated with increased perioperative mortality but with lower risk of patient-prosthesis mismatch.

Surgical aortic valve replacement and patient-prosthesis mismatch: a meta-analysis of 108 182 patients.

OBJECTIVES: This study sought to evaluate the impact of patient-prosthesis mismatch (PPM) on the risk of perioperative, early-, mid- and long-term mortality rates after surgical aortic valve replacement. METHODS: Databases were searched for studies published until March 2018. The main outcomes of interest were perioperative mortality, 1-year mortality, 5-year mortality and 10-year mortality. RESULTS: The search yielded 3761 studies for inclusion. Of these, 70 articles were analysed, and their data were extracted. The total number of patients included was 108 182 who underwent surgical aortic valve replacement. The incidence of PPM after surgical aortic valve replacement was 53.7% (58 116 with PPM and 50 066 without PPM). Perioperative mortality [odds ratio (OR) 1.491, 95% confidence interval (CI) 1.302-1.707; P < 0.001], 1-year mortality (OR 1.465, 95% CI 1.277-1.681; P < 0.001), 5-year mortality (OR 1.358, 95% CI 1.218-1.515; P < 0.001) and 10-year mortality (OR 1.534, 95% CI 1.290-1.825; P < 0.001) were increased in patients with PPM. Both severe PPM and moderate PPM were associated with increased risk of perioperative mortality, 1-year mortality, 5-year mortality and 10-year mortality when analysed together and separately, although we observed a higher risk in the group with severe PPM. CONCLUSIONS: Moderate/severe PPM increases perioperative, early-, mid- and long-term mortality rates proportionally to its severity. The findings of this study support the implementation of surgical strategies to prevent PPM in order to decrease mortality rates.

Updated Meta-analysis on the Closure of Patent Foramen Ovale in Reduction of Stroke Rates: the DEFENSE-PFO Trial Does not Change the Scenario.

OBJECTIVE: We aimed to analyze whether patent foramen ovale (PFO) closure reduces the risk of stroke, assessing also some safety outcomes after the publication of a new trial. INTRODUCTION: The clinical benefit of closing a PFO has been an open question, so it is necessary to review the current state of published medical data in regards to this subject. METHODS: MEDLINE, EMBASE, CENTRAL/CCTR, SciELO, LILACS, Google Scholar and reference lists of relevant articles were used to search for randomized controlled trials (RCTs) that reported any of the following outcomes: stroke, death, major bleeding or atrial fibrillation. Six studies fulfilled our eligibility criteria and included 3560 patients (1889 for PFO closure and 1671 for medical therapy. RESULTS: The risk ration (RR) for stroke in the "closure" group compared with the "medical therapy" showed a statistically significant difference between the groups, favouring the "closure" group (RR 0.366; 95%CI 0.171-0.782, P=0.010). There was no statistically significant difference between the groups regarding the safety outcomes, death and major bleeding, but we observed an increase in the risk of atrial fibrillation in the "closure" group (RR 4.131; 95%CI 2.293-7.443, P<0.001). We also observed that the larger the proportion of effective closure, the lower the risk of stroke. CONCLUSION: This meta-analysis found that stroke rates are lower with percutaneously implanted device closure than with medical therapy alone, being these rates modulated by the rates of hypertension, atrial septal aneurysm and effective closure. The publication of a new trial did not change the scenario in the medical literature.

Updated meta-analysis on the closure of patent foramen ovale in reduction of stroke rates: the defense-pfo trial does not change the scenario

Abstract Objective: We aimed to analyze whether patent foramen ovale (PFO) closure reduces the risk of stroke, assessing also some safety outcomes after the publication of a new trial. Introduction: The clinical benefit of closing a PFO has been an open question, so it is necessary to review the current state of published medical data in regards to this subject. Methods: MEDLINE, EMBASE, CENTRAL/CCTR, SciELO, LILACS, Google Scholar and reference lists of relevant articles were used to search for randomized controlled trials (RCTs) that reported any of the following outcomes: stroke, death, major bleeding or atrial fibrillation. Six studies fulfilled our eligibility criteria and included 3560 patients (1889 for PFO closure and 1671 for medical therapy. Results: The risk ration (RR) for stroke in the "closure" group compared with the "medical therapy" showed a statistically significant difference between the groups, favouring the "closure" group (RR 0.366; 95%CI 0.171-0.782, P=0.010). There was no statistically significant difference between the groups regarding the safety outcomes, death and major bleeding, but we observed an increase in the risk of atrial fibrillation in the "closure" group (RR 4.131; 95%CI 2.293-7.443, P<0.001). We also observed that the larger the proportion of effective closure, the lower the risk of stroke. Conclusion: This meta-analysis found that stroke rates are lower with percutaneously implanted device closure than with medical therapy alone, being these rates modulated by the rates of hypertension, atrial septal aneurysm and effective closure. The publication of a new trial did not change the scenario in the medical literature.