PMC:6537946 / 5871-13174 JSONTXT

{"project":"0_colil","denotations":[{"id":"31106338-2883575-6263","span":{"begin":398,"end":400},"obj":"2883575"},{"id":"31106338-16534009-6264","span":{"begin":777,"end":779},"obj":"16534009"},{"id":"31106338-25176015-6265","span":{"begin":1339,"end":1341},"obj":"25176015"},{"id":"31106338-8622246-6266","span":{"begin":1504,"end":1505},"obj":"8622246"},{"id":"31106338-11161934-6267","span":{"begin":1632,"end":1633},"obj":"11161934"},{"id":"31106338-27040723-6268","span":{"begin":2112,"end":2114},"obj":"27040723"},{"id":"31106338-30165632-6269","span":{"begin":2357,"end":2359},"obj":"30165632"},{"id":"31106338-15464325-6270","span":{"begin":2631,"end":2633},"obj":"15464325"},{"id":"31106338-23111018-6271","span":{"begin":3168,"end":3170},"obj":"23111018"},{"id":"31106338-30280640-6272","span":{"begin":3644,"end":3646},"obj":"30280640"},{"id":"31106338-30145927-6273","span":{"begin":3887,"end":3889},"obj":"30145927"},{"id":"31106338-8960472-6274","span":{"begin":4073,"end":4075},"obj":"8960472"},{"id":"31106338-29380177-6275","span":{"begin":4077,"end":4079},"obj":"29380177"},{"id":"31106338-15753115-6276","span":{"begin":4120,"end":4122},"obj":"15753115"},{"id":"31106338-27571011-6277","span":{"begin":4811,"end":4813},"obj":"27571011"},{"id":"31106338-11907286-6278","span":{"begin":4958,"end":4960},"obj":"11907286"},{"id":"31106338-15659722-6279","span":{"begin":5026,"end":5028},"obj":"15659722"},{"id":"31106338-28679089-6280","span":{"begin":5303,"end":5305},"obj":"28679089"},{"id":"31106338-24262348-6281","span":{"begin":5603,"end":5605},"obj":"24262348"},{"id":"31106338-11794191-6282","span":{"begin":5938,"end":5940},"obj":"11794191"},{"id":"31106338-19038734-6283","span":{"begin":6372,"end":6374},"obj":"19038734"}],"text":"CURRENT EVIDENCE-BASED TREATMENT RECOMMENDATIONS\nAccording to the American and European Guidelines, the latest treatment recommendations for heart failure remain multimodal.\n\nPharmacological treatment\nThe CONSENSUS trial investigated ‘enalapril’ more than 30 years ago; it was the first systematic evaluation of lowering the number of heart failure-associated deaths via pharmacological treatment [16]. Since then, various substances have proven effective. Postulating an annual mortality rate of 20% and a mean survival time of 4.1 years at baseline, adding an angiotensin-converting enzyme inhibitor, beta-blocker, aldosterone antagonist and an implantable cardioverter-defibrillator (ICD) decreases annual mortality by 70% and lengthens the mean survival time by 5.6 years [17]. Results from the recently published PARADIGM-HF [Prospective Comparison of ARNI (Angiotensin Receptor–Neprilysin Inhibitor) with ACEI (Angiotensin-Converting–Enzyme Inhibitor) to Determine Impact on Global Mortality and Morbidity in Heart Failure] trial demonstrated an improvement in the mortality rate in response to applying new pharmacological treatment options. Sacubitril-valsartan proved superior in reducing the risks of death and hospitalization for heart failure compared to standard medical treatment by interacting with the neurohumoral system [18].\n\nRisk factors and surgical treatment\nThe second treatment principle is to minimize the common risk factors for heart failure, such as alleviating hypertension [4]. Coronary revascularization [coronary artery bypass grafting (CABG)] for ischaemic heart disease preserves cardiac function [5] and improves outcome in combination with guideline-recommended medical therapy with excellent long-term overall mortality rates (all-cause mortality at 10 years with CABG versus optimal medical treatment: 58.9% vs 66.1%, hazard ratio 0.84, 95% confidence interval 0.73–0.97; P = 0.02; NNT = 14), as was recently demonstrated from STICH (Surgical Treatment for Ischaemic Heart Failure) and STICHES (Surgical Treatment for Ischaemic Heart Failure Extension Study) investigators [19]. The latest coronary revascularization guideline favours CABG as the preferable choice of revascularization in multivessel disease and reduced ventricular function, whereas comparable data for percutaneous coronary intervention are missing [20].\nBeneficial reverse remodelling effects induced by pharmacological heart failure treatment in ischaemic heart failure led to the development of a surgical procedure to reduce left ventricular volume and wall tension, with the expectation of a similar mortality benefit [21]. Post hoc analyses from the STICH trial added further insight to this idea: CABG with additional surgical ventricular reconstruction (SVR) in cases with postinfarction dilation proved effective. So, these data revealed that SVR continues to be important in the treatment of ischaemic cardiomyopathy, with convincing results and survival benefits whenever SVR was performed in a way that reduced the ventricular geometric parameters to an almost normal size (postoperative left ventricular systolic volume index of 70 ml/m2 or less) [22].\nSeveral interventional treatments are being investigated to address coexisting lesions, especially the treatment option using interventional edge-to-edge repair for functional mitral regurgitation associated with heart failure. The latest evidence on interventional edge-to-edge repair in this patient cohort indicates that in patients whose condition is stable and in high volume centres, this therapy can lead to survival benefits and symptomatic relief from dyspnoea [23]. However, in a more open all-comers trial on functional regurgitation, including severely impaired patients who can also be considered for a heart transplant or MCS, interventional edge-to-edge repair failed to provide a clinical benefit [24].\n\nArrhythmia therapy, electroresynchronization\nAn ICD implant to detect and alleviate life-threatening arrhythmias in patients with ischaemic and non-ischaemic cardiomyopathologies [25, 26] and cardiac resynchronization therapy [27] both play a fundamental role in the treatment of heart failure—and thus represent a pivotal recommendation in current heart failure guidelines. Remarkably, publication of the DANISH (Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischaemic Systolic Heart Failure on Mortality) trial subsequent to the last European Society of Cardiology guideline recommendation on the treatment of heart failure raised uncertainty about prophylactic ICD implants: device treatment in patients with symptomatic systolic heart failure not caused by coronary heart disease was not associated with a significantly lower long-term rate of death from any cause than was usual clinical care [28]. Basically, the latest guideline recommendations are based mainly on the MADIT-II (Multicentre Automatic Defibrillator Implantation Trial II) [29] and the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial) [30] trial, which were published more than a decade ago. But pharmacological treatment and coronary revascularization in coronary heart disease have changed fundamentally since these early trials with an impact on mortality and a significant reduction in sudden cardiac deaths [31]. Hence, current recommendations should be critically reappraised and supported by further randomized controlled trials.\n\nMechanical circulatory support\nVentricular assist devices (VADs) evolved from research involving cardiopulmonary bypass and the total artificial heart in the 1950s and 1960s [32]. With publication of the REMATCH (Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure) trial in 2001, the VAD breakthrough began following demonstration of the longer survival of heart failure candidates with VAD support in comparison to those treated with optimal medical treatment alone [33]. Increasing numbers of VAD implants are currently designated as destination therapy, although some of them were primarily implanted with a bridge-to-transplant intention. In a patient with a stabilized cardiac condition, this VAD support might frequently make further high-urgency listings for transplants superfluous, or patients do not fulfil strict heart transplant high-urgency criteria or simply no longer want a transplant [34]. Independently of the excellent long-term data for heart transplants, patients who are denied a transplant (due to older age or relevant comorbidities) or who will not survive the long high-urgency waiting time might benefit most from a permanent LVAD and attain outpatient status with acceptable quality of life (QoL) for a certain period. One current trial is examining the optimal point to implant a VAD in patients who have been given transplantable (T−) status and who are listed for a heart transplant with an increased risk of death while on the waiting list. The study was designed to compare the superiority of an early VAD implant to the current therapeutic strategy of medical heart failure treatment and assist device implantation only after serious deterioration of the patient’s condition. Final data collection for primary outcome measures is expected in August 2022 (ClinicalTrials.gov Identifier: NCT02387112)."}

{"project":"TEST0","denotations":[{"id":"31106338-197-203-6263","span":{"begin":398,"end":400},"obj":"[\"2883575\"]"},{"id":"31106338-235-241-6264","span":{"begin":777,"end":779},"obj":"[\"16534009\"]"},{"id":"31106338-190-196-6265","span":{"begin":1339,"end":1341},"obj":"[\"25176015\"]"},{"id":"31106338-123-128-6266","span":{"begin":1504,"end":1505},"obj":"[\"8622246\"]"},{"id":"31106338-124-129-6267","span":{"begin":1632,"end":1633},"obj":"[\"11161934\"]"},{"id":"31106338-237-243-6268","span":{"begin":2112,"end":2114},"obj":"[\"27040723\"]"},{"id":"31106338-236-242-6269","span":{"begin":2357,"end":2359},"obj":"[\"30165632\"]"},{"id":"31106338-230-236-6270","span":{"begin":2631,"end":2633},"obj":"[\"15464325\"]"},{"id":"31106338-233-239-6271","span":{"begin":3168,"end":3170},"obj":"[\"23111018\"]"},{"id":"31106338-232-238-6272","span":{"begin":3644,"end":3646},"obj":"[\"30280640\"]"},{"id":"31106338-229-235-6273","span":{"begin":3887,"end":3889},"obj":"[\"30145927\"]"},{"id":"31106338-135-141-6274","span":{"begin":4073,"end":4075},"obj":"[\"8960472\"]"},{"id":"31106338-139-145-6275","span":{"begin":4077,"end":4079},"obj":"[\"29380177\"]"},{"id":"31106338-182-188-6276","span":{"begin":4120,"end":4122},"obj":"[\"15753115\"]"},{"id":"31106338-235-241-6277","span":{"begin":4811,"end":4813},"obj":"[\"27571011\"]"},{"id":"31106338-142-148-6278","span":{"begin":4958,"end":4960},"obj":"[\"11907286\"]"},{"id":"31106338-210-216-6279","span":{"begin":5026,"end":5028},"obj":"[\"15659722\"]"},{"id":"31106338-221-227-6280","span":{"begin":5303,"end":5305},"obj":"[\"28679089\"]"},{"id":"31106338-144-150-6281","span":{"begin":5603,"end":5605},"obj":"[\"24262348\"]"},{"id":"31106338-232-238-6282","span":{"begin":5938,"end":5940},"obj":"[\"11794191\"]"},{"id":"31106338-228-234-6283","span":{"begin":6372,"end":6374},"obj":"[\"19038734\"]"}],"text":"CURRENT EVIDENCE-BASED TREATMENT RECOMMENDATIONS\nAccording to the American and European Guidelines, the latest treatment recommendations for heart failure remain multimodal.\n\nPharmacological treatment\nThe CONSENSUS trial investigated ‘enalapril’ more than 30 years ago; it was the first systematic evaluation of lowering the number of heart failure-associated deaths via pharmacological treatment [16]. Since then, various substances have proven effective. Postulating an annual mortality rate of 20% and a mean survival time of 4.1 years at baseline, adding an angiotensin-converting enzyme inhibitor, beta-blocker, aldosterone antagonist and an implantable cardioverter-defibrillator (ICD) decreases annual mortality by 70% and lengthens the mean survival time by 5.6 years [17]. Results from the recently published PARADIGM-HF [Prospective Comparison of ARNI (Angiotensin Receptor–Neprilysin Inhibitor) with ACEI (Angiotensin-Converting–Enzyme Inhibitor) to Determine Impact on Global Mortality and Morbidity in Heart Failure] trial demonstrated an improvement in the mortality rate in response to applying new pharmacological treatment options. Sacubitril-valsartan proved superior in reducing the risks of death and hospitalization for heart failure compared to standard medical treatment by interacting with the neurohumoral system [18].\n\nRisk factors and surgical treatment\nThe second treatment principle is to minimize the common risk factors for heart failure, such as alleviating hypertension [4]. Coronary revascularization [coronary artery bypass grafting (CABG)] for ischaemic heart disease preserves cardiac function [5] and improves outcome in combination with guideline-recommended medical therapy with excellent long-term overall mortality rates (all-cause mortality at 10 years with CABG versus optimal medical treatment: 58.9% vs 66.1%, hazard ratio 0.84, 95% confidence interval 0.73–0.97; P = 0.02; NNT = 14), as was recently demonstrated from STICH (Surgical Treatment for Ischaemic Heart Failure) and STICHES (Surgical Treatment for Ischaemic Heart Failure Extension Study) investigators [19]. The latest coronary revascularization guideline favours CABG as the preferable choice of revascularization in multivessel disease and reduced ventricular function, whereas comparable data for percutaneous coronary intervention are missing [20].\nBeneficial reverse remodelling effects induced by pharmacological heart failure treatment in ischaemic heart failure led to the development of a surgical procedure to reduce left ventricular volume and wall tension, with the expectation of a similar mortality benefit [21]. Post hoc analyses from the STICH trial added further insight to this idea: CABG with additional surgical ventricular reconstruction (SVR) in cases with postinfarction dilation proved effective. So, these data revealed that SVR continues to be important in the treatment of ischaemic cardiomyopathy, with convincing results and survival benefits whenever SVR was performed in a way that reduced the ventricular geometric parameters to an almost normal size (postoperative left ventricular systolic volume index of 70 ml/m2 or less) [22].\nSeveral interventional treatments are being investigated to address coexisting lesions, especially the treatment option using interventional edge-to-edge repair for functional mitral regurgitation associated with heart failure. The latest evidence on interventional edge-to-edge repair in this patient cohort indicates that in patients whose condition is stable and in high volume centres, this therapy can lead to survival benefits and symptomatic relief from dyspnoea [23]. However, in a more open all-comers trial on functional regurgitation, including severely impaired patients who can also be considered for a heart transplant or MCS, interventional edge-to-edge repair failed to provide a clinical benefit [24].\n\nArrhythmia therapy, electroresynchronization\nAn ICD implant to detect and alleviate life-threatening arrhythmias in patients with ischaemic and non-ischaemic cardiomyopathologies [25, 26] and cardiac resynchronization therapy [27] both play a fundamental role in the treatment of heart failure—and thus represent a pivotal recommendation in current heart failure guidelines. Remarkably, publication of the DANISH (Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischaemic Systolic Heart Failure on Mortality) trial subsequent to the last European Society of Cardiology guideline recommendation on the treatment of heart failure raised uncertainty about prophylactic ICD implants: device treatment in patients with symptomatic systolic heart failure not caused by coronary heart disease was not associated with a significantly lower long-term rate of death from any cause than was usual clinical care [28]. Basically, the latest guideline recommendations are based mainly on the MADIT-II (Multicentre Automatic Defibrillator Implantation Trial II) [29] and the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial) [30] trial, which were published more than a decade ago. But pharmacological treatment and coronary revascularization in coronary heart disease have changed fundamentally since these early trials with an impact on mortality and a significant reduction in sudden cardiac deaths [31]. Hence, current recommendations should be critically reappraised and supported by further randomized controlled trials.\n\nMechanical circulatory support\nVentricular assist devices (VADs) evolved from research involving cardiopulmonary bypass and the total artificial heart in the 1950s and 1960s [32]. With publication of the REMATCH (Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure) trial in 2001, the VAD breakthrough began following demonstration of the longer survival of heart failure candidates with VAD support in comparison to those treated with optimal medical treatment alone [33]. Increasing numbers of VAD implants are currently designated as destination therapy, although some of them were primarily implanted with a bridge-to-transplant intention. In a patient with a stabilized cardiac condition, this VAD support might frequently make further high-urgency listings for transplants superfluous, or patients do not fulfil strict heart transplant high-urgency criteria or simply no longer want a transplant [34]. Independently of the excellent long-term data for heart transplants, patients who are denied a transplant (due to older age or relevant comorbidities) or who will not survive the long high-urgency waiting time might benefit most from a permanent LVAD and attain outpatient status with acceptable quality of life (QoL) for a certain period. One current trial is examining the optimal point to implant a VAD in patients who have been given transplantable (T−) status and who are listed for a heart transplant with an increased risk of death while on the waiting list. The study was designed to compare the superiority of an early VAD implant to the current therapeutic strategy of medical heart failure treatment and assist device implantation only after serious deterioration of the patient’s condition. Final data collection for primary outcome measures is expected in August 2022 (ClinicalTrials.gov Identifier: NCT02387112)."}

{"project":"2_test","denotations":[{"id":"31106338-2883575-28904576","span":{"begin":398,"end":400},"obj":"2883575"},{"id":"31106338-16534009-28904577","span":{"begin":777,"end":779},"obj":"16534009"},{"id":"31106338-25176015-28904578","span":{"begin":1339,"end":1341},"obj":"25176015"},{"id":"31106338-8622246-28904579","span":{"begin":1504,"end":1505},"obj":"8622246"},{"id":"31106338-11161934-28904580","span":{"begin":1632,"end":1633},"obj":"11161934"},{"id":"31106338-27040723-28904581","span":{"begin":2112,"end":2114},"obj":"27040723"},{"id":"31106338-30165632-28904582","span":{"begin":2357,"end":2359},"obj":"30165632"},{"id":"31106338-15464325-28904583","span":{"begin":2631,"end":2633},"obj":"15464325"},{"id":"31106338-23111018-28904584","span":{"begin":3168,"end":3170},"obj":"23111018"},{"id":"31106338-30280640-28904585","span":{"begin":3644,"end":3646},"obj":"30280640"},{"id":"31106338-30145927-28904586","span":{"begin":3887,"end":3889},"obj":"30145927"},{"id":"31106338-8960472-28904587","span":{"begin":4073,"end":4075},"obj":"8960472"},{"id":"31106338-29380177-28904588","span":{"begin":4077,"end":4079},"obj":"29380177"},{"id":"31106338-15753115-28904589","span":{"begin":4120,"end":4122},"obj":"15753115"},{"id":"31106338-27571011-28904590","span":{"begin":4811,"end":4813},"obj":"27571011"},{"id":"31106338-11907286-28904591","span":{"begin":4958,"end":4960},"obj":"11907286"},{"id":"31106338-15659722-28904592","span":{"begin":5026,"end":5028},"obj":"15659722"},{"id":"31106338-28679089-28904593","span":{"begin":5303,"end":5305},"obj":"28679089"},{"id":"31106338-24262348-28904594","span":{"begin":5603,"end":5605},"obj":"24262348"},{"id":"31106338-11794191-28904595","span":{"begin":5938,"end":5940},"obj":"11794191"},{"id":"31106338-19038734-28904596","span":{"begin":6372,"end":6374},"obj":"19038734"}],"text":"CURRENT EVIDENCE-BASED TREATMENT RECOMMENDATIONS\nAccording to the American and European Guidelines, the latest treatment recommendations for heart failure remain multimodal.\n\nPharmacological treatment\nThe CONSENSUS trial investigated ‘enalapril’ more than 30 years ago; it was the first systematic evaluation of lowering the number of heart failure-associated deaths via pharmacological treatment [16]. Since then, various substances have proven effective. Postulating an annual mortality rate of 20% and a mean survival time of 4.1 years at baseline, adding an angiotensin-converting enzyme inhibitor, beta-blocker, aldosterone antagonist and an implantable cardioverter-defibrillator (ICD) decreases annual mortality by 70% and lengthens the mean survival time by 5.6 years [17]. Results from the recently published PARADIGM-HF [Prospective Comparison of ARNI (Angiotensin Receptor–Neprilysin Inhibitor) with ACEI (Angiotensin-Converting–Enzyme Inhibitor) to Determine Impact on Global Mortality and Morbidity in Heart Failure] trial demonstrated an improvement in the mortality rate in response to applying new pharmacological treatment options. Sacubitril-valsartan proved superior in reducing the risks of death and hospitalization for heart failure compared to standard medical treatment by interacting with the neurohumoral system [18].\n\nRisk factors and surgical treatment\nThe second treatment principle is to minimize the common risk factors for heart failure, such as alleviating hypertension [4]. Coronary revascularization [coronary artery bypass grafting (CABG)] for ischaemic heart disease preserves cardiac function [5] and improves outcome in combination with guideline-recommended medical therapy with excellent long-term overall mortality rates (all-cause mortality at 10 years with CABG versus optimal medical treatment: 58.9% vs 66.1%, hazard ratio 0.84, 95% confidence interval 0.73–0.97; P = 0.02; NNT = 14), as was recently demonstrated from STICH (Surgical Treatment for Ischaemic Heart Failure) and STICHES (Surgical Treatment for Ischaemic Heart Failure Extension Study) investigators [19]. The latest coronary revascularization guideline favours CABG as the preferable choice of revascularization in multivessel disease and reduced ventricular function, whereas comparable data for percutaneous coronary intervention are missing [20].\nBeneficial reverse remodelling effects induced by pharmacological heart failure treatment in ischaemic heart failure led to the development of a surgical procedure to reduce left ventricular volume and wall tension, with the expectation of a similar mortality benefit [21]. Post hoc analyses from the STICH trial added further insight to this idea: CABG with additional surgical ventricular reconstruction (SVR) in cases with postinfarction dilation proved effective. So, these data revealed that SVR continues to be important in the treatment of ischaemic cardiomyopathy, with convincing results and survival benefits whenever SVR was performed in a way that reduced the ventricular geometric parameters to an almost normal size (postoperative left ventricular systolic volume index of 70 ml/m2 or less) [22].\nSeveral interventional treatments are being investigated to address coexisting lesions, especially the treatment option using interventional edge-to-edge repair for functional mitral regurgitation associated with heart failure. The latest evidence on interventional edge-to-edge repair in this patient cohort indicates that in patients whose condition is stable and in high volume centres, this therapy can lead to survival benefits and symptomatic relief from dyspnoea [23]. However, in a more open all-comers trial on functional regurgitation, including severely impaired patients who can also be considered for a heart transplant or MCS, interventional edge-to-edge repair failed to provide a clinical benefit [24].\n\nArrhythmia therapy, electroresynchronization\nAn ICD implant to detect and alleviate life-threatening arrhythmias in patients with ischaemic and non-ischaemic cardiomyopathologies [25, 26] and cardiac resynchronization therapy [27] both play a fundamental role in the treatment of heart failure—and thus represent a pivotal recommendation in current heart failure guidelines. Remarkably, publication of the DANISH (Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischaemic Systolic Heart Failure on Mortality) trial subsequent to the last European Society of Cardiology guideline recommendation on the treatment of heart failure raised uncertainty about prophylactic ICD implants: device treatment in patients with symptomatic systolic heart failure not caused by coronary heart disease was not associated with a significantly lower long-term rate of death from any cause than was usual clinical care [28]. Basically, the latest guideline recommendations are based mainly on the MADIT-II (Multicentre Automatic Defibrillator Implantation Trial II) [29] and the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial) [30] trial, which were published more than a decade ago. But pharmacological treatment and coronary revascularization in coronary heart disease have changed fundamentally since these early trials with an impact on mortality and a significant reduction in sudden cardiac deaths [31]. Hence, current recommendations should be critically reappraised and supported by further randomized controlled trials.\n\nMechanical circulatory support\nVentricular assist devices (VADs) evolved from research involving cardiopulmonary bypass and the total artificial heart in the 1950s and 1960s [32]. With publication of the REMATCH (Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure) trial in 2001, the VAD breakthrough began following demonstration of the longer survival of heart failure candidates with VAD support in comparison to those treated with optimal medical treatment alone [33]. Increasing numbers of VAD implants are currently designated as destination therapy, although some of them were primarily implanted with a bridge-to-transplant intention. In a patient with a stabilized cardiac condition, this VAD support might frequently make further high-urgency listings for transplants superfluous, or patients do not fulfil strict heart transplant high-urgency criteria or simply no longer want a transplant [34]. Independently of the excellent long-term data for heart transplants, patients who are denied a transplant (due to older age or relevant comorbidities) or who will not survive the long high-urgency waiting time might benefit most from a permanent LVAD and attain outpatient status with acceptable quality of life (QoL) for a certain period. One current trial is examining the optimal point to implant a VAD in patients who have been given transplantable (T−) status and who are listed for a heart transplant with an increased risk of death while on the waiting list. The study was designed to compare the superiority of an early VAD implant to the current therapeutic strategy of medical heart failure treatment and assist device implantation only after serious deterioration of the patient’s condition. Final data collection for primary outcome measures is expected in August 2022 (ClinicalTrials.gov Identifier: NCT02387112)."}

{"project":"MyTest","denotations":[{"id":"31106338-2883575-28904576","span":{"begin":398,"end":400},"obj":"2883575"},{"id":"31106338-16534009-28904577","span":{"begin":777,"end":779},"obj":"16534009"},{"id":"31106338-25176015-28904578","span":{"begin":1339,"end":1341},"obj":"25176015"},{"id":"31106338-8622246-28904579","span":{"begin":1504,"end":1505},"obj":"8622246"},{"id":"31106338-11161934-28904580","span":{"begin":1632,"end":1633},"obj":"11161934"},{"id":"31106338-27040723-28904581","span":{"begin":2112,"end":2114},"obj":"27040723"},{"id":"31106338-30165632-28904582","span":{"begin":2357,"end":2359},"obj":"30165632"},{"id":"31106338-15464325-28904583","span":{"begin":2631,"end":2633},"obj":"15464325"},{"id":"31106338-23111018-28904584","span":{"begin":3168,"end":3170},"obj":"23111018"},{"id":"31106338-30280640-28904585","span":{"begin":3644,"end":3646},"obj":"30280640"},{"id":"31106338-30145927-28904586","span":{"begin":3887,"end":3889},"obj":"30145927"},{"id":"31106338-8960472-28904587","span":{"begin":4073,"end":4075},"obj":"8960472"},{"id":"31106338-29380177-28904588","span":{"begin":4077,"end":4079},"obj":"29380177"},{"id":"31106338-15753115-28904589","span":{"begin":4120,"end":4122},"obj":"15753115"},{"id":"31106338-27571011-28904590","span":{"begin":4811,"end":4813},"obj":"27571011"},{"id":"31106338-11907286-28904591","span":{"begin":4958,"end":4960},"obj":"11907286"},{"id":"31106338-15659722-28904592","span":{"begin":5026,"end":5028},"obj":"15659722"},{"id":"31106338-28679089-28904593","span":{"begin":5303,"end":5305},"obj":"28679089"},{"id":"31106338-24262348-28904594","span":{"begin":5603,"end":5605},"obj":"24262348"},{"id":"31106338-11794191-28904595","span":{"begin":5938,"end":5940},"obj":"11794191"},{"id":"31106338-19038734-28904596","span":{"begin":6372,"end":6374},"obj":"19038734"}],"namespaces":[{"prefix":"_base","uri":"https://www.uniprot.org/uniprot/testbase"},{"prefix":"UniProtKB","uri":"https://www.uniprot.org/uniprot/"},{"prefix":"uniprot","uri":"https://www.uniprot.org/uniprotkb/"}],"text":"CURRENT EVIDENCE-BASED TREATMENT RECOMMENDATIONS\nAccording to the American and European Guidelines, the latest treatment recommendations for heart failure remain multimodal.\n\nPharmacological treatment\nThe CONSENSUS trial investigated ‘enalapril’ more than 30 years ago; it was the first systematic evaluation of lowering the number of heart failure-associated deaths via pharmacological treatment [16]. Since then, various substances have proven effective. Postulating an annual mortality rate of 20% and a mean survival time of 4.1 years at baseline, adding an angiotensin-converting enzyme inhibitor, beta-blocker, aldosterone antagonist and an implantable cardioverter-defibrillator (ICD) decreases annual mortality by 70% and lengthens the mean survival time by 5.6 years [17]. Results from the recently published PARADIGM-HF [Prospective Comparison of ARNI (Angiotensin Receptor–Neprilysin Inhibitor) with ACEI (Angiotensin-Converting–Enzyme Inhibitor) to Determine Impact on Global Mortality and Morbidity in Heart Failure] trial demonstrated an improvement in the mortality rate in response to applying new pharmacological treatment options. Sacubitril-valsartan proved superior in reducing the risks of death and hospitalization for heart failure compared to standard medical treatment by interacting with the neurohumoral system [18].\n\nRisk factors and surgical treatment\nThe second treatment principle is to minimize the common risk factors for heart failure, such as alleviating hypertension [4]. Coronary revascularization [coronary artery bypass grafting (CABG)] for ischaemic heart disease preserves cardiac function [5] and improves outcome in combination with guideline-recommended medical therapy with excellent long-term overall mortality rates (all-cause mortality at 10 years with CABG versus optimal medical treatment: 58.9% vs 66.1%, hazard ratio 0.84, 95% confidence interval 0.73–0.97; P = 0.02; NNT = 14), as was recently demonstrated from STICH (Surgical Treatment for Ischaemic Heart Failure) and STICHES (Surgical Treatment for Ischaemic Heart Failure Extension Study) investigators [19]. The latest coronary revascularization guideline favours CABG as the preferable choice of revascularization in multivessel disease and reduced ventricular function, whereas comparable data for percutaneous coronary intervention are missing [20].\nBeneficial reverse remodelling effects induced by pharmacological heart failure treatment in ischaemic heart failure led to the development of a surgical procedure to reduce left ventricular volume and wall tension, with the expectation of a similar mortality benefit [21]. Post hoc analyses from the STICH trial added further insight to this idea: CABG with additional surgical ventricular reconstruction (SVR) in cases with postinfarction dilation proved effective. So, these data revealed that SVR continues to be important in the treatment of ischaemic cardiomyopathy, with convincing results and survival benefits whenever SVR was performed in a way that reduced the ventricular geometric parameters to an almost normal size (postoperative left ventricular systolic volume index of 70 ml/m2 or less) [22].\nSeveral interventional treatments are being investigated to address coexisting lesions, especially the treatment option using interventional edge-to-edge repair for functional mitral regurgitation associated with heart failure. The latest evidence on interventional edge-to-edge repair in this patient cohort indicates that in patients whose condition is stable and in high volume centres, this therapy can lead to survival benefits and symptomatic relief from dyspnoea [23]. However, in a more open all-comers trial on functional regurgitation, including severely impaired patients who can also be considered for a heart transplant or MCS, interventional edge-to-edge repair failed to provide a clinical benefit [24].\n\nArrhythmia therapy, electroresynchronization\nAn ICD implant to detect and alleviate life-threatening arrhythmias in patients with ischaemic and non-ischaemic cardiomyopathologies [25, 26] and cardiac resynchronization therapy [27] both play a fundamental role in the treatment of heart failure—and thus represent a pivotal recommendation in current heart failure guidelines. Remarkably, publication of the DANISH (Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischaemic Systolic Heart Failure on Mortality) trial subsequent to the last European Society of Cardiology guideline recommendation on the treatment of heart failure raised uncertainty about prophylactic ICD implants: device treatment in patients with symptomatic systolic heart failure not caused by coronary heart disease was not associated with a significantly lower long-term rate of death from any cause than was usual clinical care [28]. Basically, the latest guideline recommendations are based mainly on the MADIT-II (Multicentre Automatic Defibrillator Implantation Trial II) [29] and the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial) [30] trial, which were published more than a decade ago. But pharmacological treatment and coronary revascularization in coronary heart disease have changed fundamentally since these early trials with an impact on mortality and a significant reduction in sudden cardiac deaths [31]. Hence, current recommendations should be critically reappraised and supported by further randomized controlled trials.\n\nMechanical circulatory support\nVentricular assist devices (VADs) evolved from research involving cardiopulmonary bypass and the total artificial heart in the 1950s and 1960s [32]. With publication of the REMATCH (Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure) trial in 2001, the VAD breakthrough began following demonstration of the longer survival of heart failure candidates with VAD support in comparison to those treated with optimal medical treatment alone [33]. Increasing numbers of VAD implants are currently designated as destination therapy, although some of them were primarily implanted with a bridge-to-transplant intention. In a patient with a stabilized cardiac condition, this VAD support might frequently make further high-urgency listings for transplants superfluous, or patients do not fulfil strict heart transplant high-urgency criteria or simply no longer want a transplant [34]. Independently of the excellent long-term data for heart transplants, patients who are denied a transplant (due to older age or relevant comorbidities) or who will not survive the long high-urgency waiting time might benefit most from a permanent LVAD and attain outpatient status with acceptable quality of life (QoL) for a certain period. One current trial is examining the optimal point to implant a VAD in patients who have been given transplantable (T−) status and who are listed for a heart transplant with an increased risk of death while on the waiting list. The study was designed to compare the superiority of an early VAD implant to the current therapeutic strategy of medical heart failure treatment and assist device implantation only after serious deterioration of the patient’s condition. Final data collection for primary outcome measures is expected in August 2022 (ClinicalTrials.gov Identifier: NCT02387112)."}

{"project":"testtesttest","denotations":[{"id":"T168","span":{"begin":141,"end":146},"obj":"Body_part"},{"id":"T172","span":{"begin":335,"end":340},"obj":"Body_part"},{"id":"T176","span":{"begin":1015,"end":1020},"obj":"Body_part"},{"id":"T180","span":{"begin":1241,"end":1246},"obj":"Body_part"},{"id":"T184","span":{"begin":1331,"end":1337},"obj":"Body_part"},{"id":"T185","span":{"begin":1455,"end":1460},"obj":"Body_part"},{"id":"T189","span":{"begin":1536,"end":1551},"obj":"Body_part"},{"id":"T190","span":{"begin":1590,"end":1595},"obj":"Body_part"},{"id":"T194","span":{"begin":2005,"end":2010},"obj":"Body_part"},{"id":"T198","span":{"begin":2066,"end":2071},"obj":"Body_part"},{"id":"T202","span":{"begin":2080,"end":2089},"obj":"Body_part"},{"id":"T203","span":{"begin":2428,"end":2433},"obj":"Body_part"},{"id":"T207","span":{"begin":2465,"end":2470},"obj":"Body_part"},{"id":"T211","span":{"begin":2564,"end":2568},"obj":"Body_part"},{"id":"T212","span":{"begin":3386,"end":3391},"obj":"Body_part"},{"id":"T216","span":{"begin":3789,"end":3794},"obj":"Body_part"},{"id":"T220","span":{"begin":4173,"end":4178},"obj":"Body_part"},{"id":"T224","span":{"begin":4242,"end":4247},"obj":"Body_part"},{"id":"T228","span":{"begin":4391,"end":4396},"obj":"Body_part"},{"id":"T232","span":{"begin":4524,"end":4529},"obj":"Body_part"},{"id":"T236","span":{"begin":4645,"end":4650},"obj":"Body_part"},{"id":"T240","span":{"begin":4682,"end":4687},"obj":"Body_part"},{"id":"T244","span":{"begin":5004,"end":5009},"obj":"Body_part"},{"id":"T248","span":{"begin":5155,"end":5160},"obj":"Body_part"},{"id":"T252","span":{"begin":5573,"end":5578},"obj":"Body_part"},{"id":"T256","span":{"begin":5720,"end":5725},"obj":"Body_part"},{"id":"T260","span":{"begin":5827,"end":5832},"obj":"Body_part"},{"id":"T264","span":{"begin":6294,"end":6299},"obj":"Body_part"},{"id":"T268","span":{"begin":6427,"end":6432},"obj":"Body_part"},{"id":"T272","span":{"begin":6867,"end":6872},"obj":"Body_part"},{"id":"T276","span":{"begin":7064,"end":7069},"obj":"Body_part"}],"attributes":[{"id":"A168","pred":"uberon_id","subj":"T168","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A169","pred":"uberon_id","subj":"T168","obj":"http://purl.obolibrary.org/obo/UBERON_0007100"},{"id":"A170","pred":"uberon_id","subj":"T168","obj":"http://purl.obolibrary.org/obo/UBERON_0015228"},{"id":"A171","pred":"uberon_id","subj":"T168","obj":"http://purl.obolibrary.org/obo/UBERON_0015230"},{"id":"A172","pred":"uberon_id","subj":"T172","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A173","pred":"uberon_id","subj":"T172","obj":"http://purl.obolibrary.org/obo/UBERON_0007100"},{"id":"A174","pred":"uberon_id","subj":"T172","obj":"http://purl.obolibrary.org/obo/UBERON_0015228"},{"id":"A175","pred":"uberon_id","subj":"T172","obj":"http://purl.obolibrary.org/obo/UBERON_0015230"},{"id":"A176","pred":"uberon_id","subj":"T176","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A177","pred":"uberon_id","subj":"T176","obj":"http://purl.obolibrary.org/obo/UBERON_0007100"},{"id":"A178","pred":"uberon_id","subj":"T176","obj":"http://purl.obolibrary.org/obo/UBERON_0015228"},{"id":"A179","pred":"uberon_id","subj":"T176","obj":"http://purl.obolibrary.org/obo/UBERON_0015230"},{"id":"A180","pred":"uberon_id","subj":"T180","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A181","pred":"uberon_id","subj":"T180","obj":"http://purl.obolibrary.org/obo/UBERON_0007100"},{"id":"A182","pred":"uberon_id","subj":"T180","obj":"http://purl.obolibrary.org/obo/UBERON_0015228"},{"id":"A183","pred":"uberon_id","subj":"T180","obj":"http://purl.obolibrary.org/obo/UBERON_0015230"},{"id":"A184","pred":"uberon_id","subj":"T184","obj":"http://purl.obolibrary.org/obo/UBERON_0000467"},{"id":"A185","pred":"uberon_id","subj":"T185","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A186","pred":"uberon_id","subj":"T185","obj":"http://purl.obolibrary.org/obo/UBERON_0007100"},{"id":"A187","pred":"uberon_id","subj":"T185","obj":"http://purl.obolibrary.org/obo/UBERON_0015228"},{"id":"A188","pred":"uberon_id","subj":"T185","obj":"http://purl.obolibrary.org/obo/UBERON_0015230"},{"id":"A189","pred":"uberon_id","subj":"T189","obj":"http://purl.obolibrary.org/obo/UBERON_0001621"},{"id":"A190","pred":"uberon_id","subj":"T190","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A191","pred":"uberon_id","subj":"T190","obj":"http://purl.obolibrary.org/obo/UBERON_0007100"},{"id":"A192","pred":"uberon_id","subj":"T190","obj":"http://purl.obolibrary.org/obo/UBERON_0015228"},{"id":"A193","pred":"uberon_id","subj":"T190","obj":"http://purl.obolibrary.org/obo/UBERON_0015230"},{"id":"A194","pred":"uberon_id","subj":"T194","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A195","pred":"uberon_id","subj":"T194","obj":"http://purl.obolibrary.org/obo/UBERON_0007100"},{"id":"A196","pred":"uberon_id","subj":"T194","obj":"http://purl.obolibrary.org/obo/UBERON_0015228"},{"id":"A197","pred":"uberon_id","subj":"T194","obj":"http://purl.obolibrary.org/obo/UBERON_0015230"},{"id":"A198","pred":"uberon_id","subj":"T198","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A199","pred":"uberon_id","subj":"T198","obj":"http://purl.obolibrary.org/obo/UBERON_0007100"},{"id":"A200","pred":"uberon_id","subj":"T198","obj":"http://purl.obolibrary.org/obo/UBERON_0015228"},{"id":"A201","pred":"uberon_id","subj":"T198","obj":"http://purl.obolibrary.org/obo/UBERON_0015230"},{"id":"A202","pred":"uberon_id","subj":"T202","obj":"http://purl.obolibrary.org/obo/UBERON_2000106"},{"id":"A203","pred":"uberon_id","subj":"T203","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A204","pred":"uberon_id","subj":"T203","obj":"http://purl.obolibrary.org/obo/UBERON_0007100"},{"id":"A205","pred":"uberon_id","subj":"T203","obj":"http://purl.obolibrary.org/obo/UBERON_0015228"},{"id":"A206","pred":"uberon_id","subj":"T203","obj":"http://purl.obolibrary.org/obo/UBERON_0015230"},{"id":"A207","pred":"uberon_id","subj":"T207","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A208","pred":"uberon_id","subj":"T207","obj":"http://purl.obolibrary.org/obo/UBERON_0007100"},{"id":"A209","pred":"uberon_id","subj":"T207","obj":"http://purl.obolibrary.org/obo/UBERON_0015228"},{"id":"A210","pred":"uberon_id","subj":"T207","obj":"http://purl.obolibrary.org/obo/UBERON_0015230"},{"id":"A211","pred":"uberon_id","subj":"T211","obj":"http://purl.obolibrary.org/obo/UBERON_0000060"},{"id":"A212","pred":"uberon_id","subj":"T212","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A213","pred":"uberon_id","subj":"T212","obj":"http://purl.obolibrary.org/obo/UBERON_0007100"},{"id":"A214","pred":"uberon_id","subj":"T212","obj":"http://purl.obolibrary.org/obo/UBERON_0015228"},{"id":"A215","pred":"uberon_id","subj":"T212","obj":"http://purl.obolibrary.org/obo/UBERON_0015230"},{"id":"A216","pred":"uberon_id","subj":"T216","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A217","pred":"uberon_id","subj":"T216","obj":"http://purl.obolibrary.org/obo/UBERON_0007100"},{"id":"A218","pred":"uberon_id","subj":"T216","obj":"http://purl.obolibrary.org/obo/UBERON_0015228"},{"id":"A219","pred":"uberon_id","subj":"T216","obj":"http://purl.obolibrary.org/obo/UBERON_0015230"},{"id":"A220","pred":"uberon_id","subj":"T220","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A221","pred":"uberon_id","subj":"T220","obj":"http://purl.obolibrary.org/obo/UBERON_0007100"},{"id":"A222","pred":"uberon_id","subj":"T220","obj":"http://purl.obolibrary.org/obo/UBERON_0015228"},{"id":"A223","pred":"uberon_id","subj":"T220","obj":"http://purl.obolibrary.org/obo/UBERON_0015230"},{"id":"A224","pred":"uberon_id","subj":"T224","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A225","pred":"uberon_id","subj":"T224","obj":"http://purl.obolibrary.org/obo/UBERON_0007100"},{"id":"A226","pred":"uberon_id","subj":"T224","obj":"http://purl.obolibrary.org/obo/UBERON_0015228"},{"id":"A227","pred":"uberon_id","subj":"T224","obj":"http://purl.obolibrary.org/obo/UBERON_0015230"},{"id":"A228","pred":"uberon_id","subj":"T228","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A229","pred":"uberon_id","subj":"T228","obj":"http://purl.obolibrary.org/obo/UBERON_0007100"},{"id":"A230","pred":"uberon_id","subj":"T228","obj":"http://purl.obolibrary.org/obo/UBERON_0015228"},{"id":"A231","pred":"uberon_id","subj":"T228","obj":"http://purl.obolibrary.org/obo/UBERON_0015230"},{"id":"A232","pred":"uberon_id","subj":"T232","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A233","pred":"uberon_id","subj":"T232","obj":"http://purl.obolibrary.org/obo/UBERON_0007100"},{"id":"A234","pred":"uberon_id","subj":"T232","obj":"http://purl.obolibrary.org/obo/UBERON_0015228"},{"id":"A235","pred":"uberon_id","subj":"T232","obj":"http://purl.obolibrary.org/obo/UBERON_0015230"},{"id":"A236","pred":"uberon_id","subj":"T236","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A237","pred":"uberon_id","subj":"T236","obj":"http://purl.obolibrary.org/obo/UBERON_0007100"},{"id":"A238","pred":"uberon_id","subj":"T236","obj":"http://purl.obolibrary.org/obo/UBERON_0015228"},{"id":"A239","pred":"uberon_id","subj":"T236","obj":"http://purl.obolibrary.org/obo/UBERON_0015230"},{"id":"A240","pred":"uberon_id","subj":"T240","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A241","pred":"uberon_id","subj":"T240","obj":"http://purl.obolibrary.org/obo/UBERON_0007100"},{"id":"A242","pred":"uberon_id","subj":"T240","obj":"http://purl.obolibrary.org/obo/UBERON_0015228"},{"id":"A243","pred":"uberon_id","subj":"T240","obj":"http://purl.obolibrary.org/obo/UBERON_0015230"},{"id":"A244","pred":"uberon_id","subj":"T244","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A245","pred":"uberon_id","subj":"T244","obj":"http://purl.obolibrary.org/obo/UBERON_0007100"},{"id":"A246","pred":"uberon_id","subj":"T244","obj":"http://purl.obolibrary.org/obo/UBERON_0015228"},{"id":"A247","pred":"uberon_id","subj":"T244","obj":"http://purl.obolibrary.org/obo/UBERON_0015230"},{"id":"A248","pred":"uberon_id","subj":"T248","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A249","pred":"uberon_id","subj":"T248","obj":"http://purl.obolibrary.org/obo/UBERON_0007100"},{"id":"A250","pred":"uberon_id","subj":"T248","obj":"http://purl.obolibrary.org/obo/UBERON_0015228"},{"id":"A251","pred":"uberon_id","subj":"T248","obj":"http://purl.obolibrary.org/obo/UBERON_0015230"},{"id":"A252","pred":"uberon_id","subj":"T252","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A253","pred":"uberon_id","subj":"T252","obj":"http://purl.obolibrary.org/obo/UBERON_0007100"},{"id":"A254","pred":"uberon_id","subj":"T252","obj":"http://purl.obolibrary.org/obo/UBERON_0015228"},{"id":"A255","pred":"uberon_id","subj":"T252","obj":"http://purl.obolibrary.org/obo/UBERON_0015230"},{"id":"A256","pred":"uberon_id","subj":"T256","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A257","pred":"uberon_id","subj":"T256","obj":"http://purl.obolibrary.org/obo/UBERON_0007100"},{"id":"A258","pred":"uberon_id","subj":"T256","obj":"http://purl.obolibrary.org/obo/UBERON_0015228"},{"id":"A259","pred":"uberon_id","subj":"T256","obj":"http://purl.obolibrary.org/obo/UBERON_0015230"},{"id":"A260","pred":"uberon_id","subj":"T260","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A261","pred":"uberon_id","subj":"T260","obj":"http://purl.obolibrary.org/obo/UBERON_0007100"},{"id":"A262","pred":"uberon_id","subj":"T260","obj":"http://purl.obolibrary.org/obo/UBERON_0015228"},{"id":"A263","pred":"uberon_id","subj":"T260","obj":"http://purl.obolibrary.org/obo/UBERON_0015230"},{"id":"A264","pred":"uberon_id","subj":"T264","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A265","pred":"uberon_id","subj":"T264","obj":"http://purl.obolibrary.org/obo/UBERON_0007100"},{"id":"A266","pred":"uberon_id","subj":"T264","obj":"http://purl.obolibrary.org/obo/UBERON_0015228"},{"id":"A267","pred":"uberon_id","subj":"T264","obj":"http://purl.obolibrary.org/obo/UBERON_0015230"},{"id":"A268","pred":"uberon_id","subj":"T268","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A269","pred":"uberon_id","subj":"T268","obj":"http://purl.obolibrary.org/obo/UBERON_0007100"},{"id":"A270","pred":"uberon_id","subj":"T268","obj":"http://purl.obolibrary.org/obo/UBERON_0015228"},{"id":"A271","pred":"uberon_id","subj":"T268","obj":"http://purl.obolibrary.org/obo/UBERON_0015230"},{"id":"A272","pred":"uberon_id","subj":"T272","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A273","pred":"uberon_id","subj":"T272","obj":"http://purl.obolibrary.org/obo/UBERON_0007100"},{"id":"A274","pred":"uberon_id","subj":"T272","obj":"http://purl.obolibrary.org/obo/UBERON_0015228"},{"id":"A275","pred":"uberon_id","subj":"T272","obj":"http://purl.obolibrary.org/obo/UBERON_0015230"},{"id":"A276","pred":"uberon_id","subj":"T276","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A277","pred":"uberon_id","subj":"T276","obj":"http://purl.obolibrary.org/obo/UBERON_0007100"},{"id":"A278","pred":"uberon_id","subj":"T276","obj":"http://purl.obolibrary.org/obo/UBERON_0015228"},{"id":"A279","pred":"uberon_id","subj":"T276","obj":"http://purl.obolibrary.org/obo/UBERON_0015230"}],"text":"CURRENT EVIDENCE-BASED TREATMENT RECOMMENDATIONS\nAccording to the American and European Guidelines, the latest treatment recommendations for heart failure remain multimodal.\n\nPharmacological treatment\nThe CONSENSUS trial investigated ‘enalapril’ more than 30 years ago; it was the first systematic evaluation of lowering the number of heart failure-associated deaths via pharmacological treatment [16]. Since then, various substances have proven effective. Postulating an annual mortality rate of 20% and a mean survival time of 4.1 years at baseline, adding an angiotensin-converting enzyme inhibitor, beta-blocker, aldosterone antagonist and an implantable cardioverter-defibrillator (ICD) decreases annual mortality by 70% and lengthens the mean survival time by 5.6 years [17]. Results from the recently published PARADIGM-HF [Prospective Comparison of ARNI (Angiotensin Receptor–Neprilysin Inhibitor) with ACEI (Angiotensin-Converting–Enzyme Inhibitor) to Determine Impact on Global Mortality and Morbidity in Heart Failure] trial demonstrated an improvement in the mortality rate in response to applying new pharmacological treatment options. Sacubitril-valsartan proved superior in reducing the risks of death and hospitalization for heart failure compared to standard medical treatment by interacting with the neurohumoral system [18].\n\nRisk factors and surgical treatment\nThe second treatment principle is to minimize the common risk factors for heart failure, such as alleviating hypertension [4]. Coronary revascularization [coronary artery bypass grafting (CABG)] for ischaemic heart disease preserves cardiac function [5] and improves outcome in combination with guideline-recommended medical therapy with excellent long-term overall mortality rates (all-cause mortality at 10 years with CABG versus optimal medical treatment: 58.9% vs 66.1%, hazard ratio 0.84, 95% confidence interval 0.73–0.97; P = 0.02; NNT = 14), as was recently demonstrated from STICH (Surgical Treatment for Ischaemic Heart Failure) and STICHES (Surgical Treatment for Ischaemic Heart Failure Extension Study) investigators [19]. The latest coronary revascularization guideline favours CABG as the preferable choice of revascularization in multivessel disease and reduced ventricular function, whereas comparable data for percutaneous coronary intervention are missing [20].\nBeneficial reverse remodelling effects induced by pharmacological heart failure treatment in ischaemic heart failure led to the development of a surgical procedure to reduce left ventricular volume and wall tension, with the expectation of a similar mortality benefit [21]. Post hoc analyses from the STICH trial added further insight to this idea: CABG with additional surgical ventricular reconstruction (SVR) in cases with postinfarction dilation proved effective. So, these data revealed that SVR continues to be important in the treatment of ischaemic cardiomyopathy, with convincing results and survival benefits whenever SVR was performed in a way that reduced the ventricular geometric parameters to an almost normal size (postoperative left ventricular systolic volume index of 70 ml/m2 or less) [22].\nSeveral interventional treatments are being investigated to address coexisting lesions, especially the treatment option using interventional edge-to-edge repair for functional mitral regurgitation associated with heart failure. The latest evidence on interventional edge-to-edge repair in this patient cohort indicates that in patients whose condition is stable and in high volume centres, this therapy can lead to survival benefits and symptomatic relief from dyspnoea [23]. However, in a more open all-comers trial on functional regurgitation, including severely impaired patients who can also be considered for a heart transplant or MCS, interventional edge-to-edge repair failed to provide a clinical benefit [24].\n\nArrhythmia therapy, electroresynchronization\nAn ICD implant to detect and alleviate life-threatening arrhythmias in patients with ischaemic and non-ischaemic cardiomyopathologies [25, 26] and cardiac resynchronization therapy [27] both play a fundamental role in the treatment of heart failure—and thus represent a pivotal recommendation in current heart failure guidelines. Remarkably, publication of the DANISH (Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischaemic Systolic Heart Failure on Mortality) trial subsequent to the last European Society of Cardiology guideline recommendation on the treatment of heart failure raised uncertainty about prophylactic ICD implants: device treatment in patients with symptomatic systolic heart failure not caused by coronary heart disease was not associated with a significantly lower long-term rate of death from any cause than was usual clinical care [28]. Basically, the latest guideline recommendations are based mainly on the MADIT-II (Multicentre Automatic Defibrillator Implantation Trial II) [29] and the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial) [30] trial, which were published more than a decade ago. But pharmacological treatment and coronary revascularization in coronary heart disease have changed fundamentally since these early trials with an impact on mortality and a significant reduction in sudden cardiac deaths [31]. Hence, current recommendations should be critically reappraised and supported by further randomized controlled trials.\n\nMechanical circulatory support\nVentricular assist devices (VADs) evolved from research involving cardiopulmonary bypass and the total artificial heart in the 1950s and 1960s [32]. With publication of the REMATCH (Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure) trial in 2001, the VAD breakthrough began following demonstration of the longer survival of heart failure candidates with VAD support in comparison to those treated with optimal medical treatment alone [33]. Increasing numbers of VAD implants are currently designated as destination therapy, although some of them were primarily implanted with a bridge-to-transplant intention. In a patient with a stabilized cardiac condition, this VAD support might frequently make further high-urgency listings for transplants superfluous, or patients do not fulfil strict heart transplant high-urgency criteria or simply no longer want a transplant [34]. Independently of the excellent long-term data for heart transplants, patients who are denied a transplant (due to older age or relevant comorbidities) or who will not survive the long high-urgency waiting time might benefit most from a permanent LVAD and attain outpatient status with acceptable quality of life (QoL) for a certain period. One current trial is examining the optimal point to implant a VAD in patients who have been given transplantable (T−) status and who are listed for a heart transplant with an increased risk of death while on the waiting list. The study was designed to compare the superiority of an early VAD implant to the current therapeutic strategy of medical heart failure treatment and assist device implantation only after serious deterioration of the patient’s condition. Final data collection for primary outcome measures is expected in August 2022 (ClinicalTrials.gov Identifier: NCT02387112)."}