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Despite progressive improvement in medical therapy and standard care, the exercise capacity of heart transplant recipients is reduced compared with age-matched healthy individuals. Exercise-based rehabilitation programs have been shown to improve the exercise capacity of transplant patients through a multifactorial effect. In this context, high-intensity interval exercise is a growing field of research, with current evidence suggesting a major benefit in heart transplant recipients compared with a conventional training protocol. Therefore, this study aimed to provide an overview of the mechanisms involved in the reduced exercise capacity of heart transplant patients and a review of current rehabilitation strategies with a special focus on the mechanisms and clinical effects of high-intensity interval training exercise.
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Transplante de Coração , Treinamento Intervalado de Alta Intensidade , Exercício Físico , Terapia por Exercício , Tolerância ao Exercício , Humanos , TransplantadosRESUMO
Advanced heart failure, an end-stage disease characterized by high mortality and morbidity despite standard medical therapy, requires various therapeutic strategies like heart transplant and long-term mechanical circulatory support. Echocardiography is the main imaging technique to identify transitions to advanced stages of disease and guide risk stratification and therapeutic decision-making processes. Progressive development of advanced echocardiographic techniques allows more comprehensive assessment of the hemodynamic and structural profiles of patients with advanced heart failure, and its use in clinical practice continues to expand. This article provides an overview of basic and emerging echocardiographic tools to assess patients with advanced heart failure.
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Insuficiência Cardíaca , Transplante de Coração , Ecocardiografia , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/terapia , Hemodinâmica , Humanos , PrognósticoRESUMO
BACKGROUND: Heart failure (HF) progression and its complications represent major emergent concerns in hypertrophic cardiomyopathy (HCM). We investigated the possible adjunctive role of cardiopulmonary exercise testing (CPET) in predicting HF-related events. An exercise-derived risk model, theHYPertrophicExercise-derivedRiskHF(HYPERHF), has been developed. METHODSâANDâRESULTS: A multicenter cohort of 620 consecutive HCM outpatients was recruited and followed (2007 to 2015). The endpoint was death from HF, cardiac transplantation, NYHA III-IV class progression, severe functional deterioration leading to hospitalization for septal reduction, and hospitalization for HF worsening. During a median follow-up of 3.8 years (25-75th centile: 2.3-5.3 years), 84 patients reached the endpoint. Peak circulatory power (peak oxygen consumption * peak systolic blood pressure), ventilatory efficiency and left atrial diameter were independently associated with the endpoint and, accordingly, integrated into the HYPERHFmodel (C index: 0.849; best cutoff value equal to 15%). CONCLUSIONS: CPET is useful in the evaluation of HCM patients. In this context, the HYPERHFscore might allow early identification of those patients at high risk of HF progression and its complications. (Circ J 2016; 80: 2204-2211).
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Cardiomiopatia Hipertrófica , Teste de Esforço , Insuficiência Cardíaca , Adulto , Idoso , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/fisiopatologia , Estudos de Coortes , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
Heart failure (HF) is a complex and progressive disease marked by substantial morbidity and mortality rates, frequent episodes of decompensation, and a reduced quality of life (QoL), with severe financial burden on healthcare systems. In recent years, several large-scale randomized clinical trials (RCTs) have widely expanded the therapeutic armamentarium, underlining additional benefits and the feasibility of rapid titration regimens. This notwithstanding, mortality is not declining, and hospitalizations are constantly increasing. It is widely acknowledged that even with guideline-directed medical therapy (GDMT) on board, HF patients have a prohibitive residual risk, which highlights the need for innovative treatment options. In this scenario, groundbreaking devices targeting valvular, structural, and autonomic abnormalities have become crucial tools in HF management. This has led to a full-fledged translational boost with several novel devices in development. Thus, the aim of this review is to provide an update on both approved and investigated devices.
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Current advances in plant genotyping lead to major progress in the knowledge of genetic architecture of traits of interest. It is increasingly important to develop decision support tools to help breeders and geneticists to conduct marker-assisted selection methods to assemble favorable alleles that are discovered. Algorithms have been implemented, within an interactive graphical interface, to 1) trace parental alleles throughout generations, 2) propose strategies to select the best plants based on estimated molecular scores, and 3) efficiently intermate them depending on the expected value of their progenies. With the possibility to consider a multi-allelic context, OptiMAS opens new prospects to assemble favorable alleles issued from diverse parents and further accelerate genetic gain.
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Algoritmos , Alelos , Técnicas de Apoio para a Decisão , Marcadores Genéticos/fisiologia , Variação Genética , Cruzamento/métodos , Mapeamento Cromossômico/métodos , Genes de Plantas/fisiologia , Fenótipo , Filogenia , Plantas/genética , Locos de Características Quantitativas/genética , Locos de Características Quantitativas/fisiologia , Seleção Genética/genéticaRESUMO
Even though acute heart failure (AHF) is one of the most common admission diagnoses globally, its pathogenesis is poorly understood, and there are few effective treatments available. Despite an heterogenous onset, congestion is the leading contributor to hospitalization, making it a crucial therapeutic target. Complete decongestion, nevertheless, may be hard to achieve, especially in patients with reduced end organ perfusion. In order to promote a personalised pathophysiological-based therapy for patients with AHF, we will address in this review the pathophysiological principles that underlie the clinical symptoms of AHF as well as examine how to assess them in clinical practice, suggesting that gaining a deeper understanding of pathophysiology might result in significant improvements in HF therapy.
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Heart failure with reduced ejection fraction is a chronic and progressive syndrome that continues to be a substantial financial burden for health systems in Western countries. Despite remarkable advances in pharmacologic and device-based therapy over the last few years, patients with heart failure with reduced ejection fraction have a high residual risk of adverse outcomes, even when treated with optimal guideline-directed medical therapy and in a clinically stable state. Worsening heart failure episodes represent a critical event in the heart failure trajectory, carrying high residual risk at discharge and dismal short- or long-term prognosis. Recently, vericiguat, a soluble guanylate cyclase stimulator, has been proposed as a novel drug whose use is already associated with a reduction in heart failure-related hospitalizations in patients in guideline-directed medical therapy. In this review, we summarized the pathophysiology of the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate cascade in patients with heart failure with reduced ejection fraction, the pharmacology of vericiguat as well as the evidence regarding their use in patients with HFrEF. Finally, tips and tricks for its use in standard clinical practice are provided.
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In recent years, a significant improvement in left ventricular assist device (LVAD) technology has occurred, and the continuous-flow devices currently used can last more than 10 years in a patient. Current studies report that the 5-year survival rate after LVAD implantation approaches that after a heart transplant. However, the outcome is influenced by the correct selection of the patients, as well as the choice of the optimal time for implantation. This review summarizes the indications, the red flags for prompt initiation of LVAD evaluation, and the principles for appropriate patient screening.
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Cardiac contractility modulation (CCM) is a novel device-based therapy in patients with heart failure with reduced ejection fraction (HFrEF). In randomized clinical trials and real-life studies, CCM has been shown to improve exercise tolerance and quality of life, reverse left ventricular remodeling and reduce hospitalization in patients with HFrEF. In this case report, we describe for the first time the use of CCM as a "bridge to transplant" in a young obese patient with advanced heart failure due to non-ischemic dilated cardiomyopathy. The patient had a poor quality of life and frequent heart failure-related hospitalizations despite the optimal medical therapy and, due to obesity, a suitable heart donor was unlikely to be identified in the short term and due to severe obesity risk of complications after implantation of a left ventricular assist device (LVAD) was very high.
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Background: Patients with advanced heart failure with reduced ejection fraction often cannot tolerate target doses of guideline-directed medical therapy due to symptomatic hypotension, renal dysfunction, and associated electrolyte abnormalities. While levosimendan can facilitate the titration of ß-blockers in patients with advanced HFrEF, it is unclear whether ambulatory levosimendan infusions would offer the same benefit. In this prospective study, we investigate the effects of intermittent ambulatory levosimendan infusions on the uptitration of disease-modifying drugs. Methods: We enrolled 37 patients with advanced HFrEF who received repeated ambulatory infusions of levosimendan between January 2018 and January 2021. The demographic, clinical, and laboratory data were acquired 24 h before the first and the last ambulatory levosimendan infusion. Results: At the 1 year follow-up, the enrolled patients were on significantly higher doses of guideline-directed medical therapy, including bisoprolol (3.2 ± 2.8 mg vs. 5.9 ± 4.1 mg; p = 0.02), sacubitril/valsartan (41.67 ± 32.48 mg vs. 68.5 ± 35.72 mg; p = 0.01), and eplerenone (12.7 ± 8.5 mg vs. 22.8 ± 13.6 mg; p = 0.03). Furthermore, a substantial decrease in the furosemide dose was observed (123.2 ± 32.48 mg vs. 81.6 ± 19.47 mg; p < 0.0001). Conclusions: Levosimendan facilitates the optimization of disease-modifying heart failure medications in previously intolerant advanced HFrEF patients.
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BACKGROUND: The worsening of renal function after the start of valsartan therapy is relatively common in clinical practice. However, few data are available on the incidence of worsening renal function after the beginning of therapy with sacubitril/valsartan. METHODS: We retrospectively enrolled 202 outpatients with HFrEF that started therapy with sacubitril/valsartan to evaluate the prevalence of worsening renal function and its clinical significance. RESULTS: At 1 month, a worsening renal function (defined as a > 20% decrease in eGFR occurring after 1 month of ARNi therapy) was found in 68 patients (33%), however after a mean follow-up of 650 ± 80 days, Kaplan-Meier analysis showed no significant in terms of HF-related deaths, HF-related hospitalizations, and the need for renal replacement therapy (25.2 vs. 23.6%; p = .812). In addition, the renal function recovered in patients with early WRF at 3 months (62 + 9.3 ml/min/1.73 m2 vs. 63 ± 13.8 ml/min/1.73 m2; p < .05), with an improvement in estimated glomerular filtration rate at 1 year compared with baseline value (62 ± 9.3 ml/min/1.73 m2 vs. 69 ± 8.6 ml/min/1.73 m2; p < .01). CONCLUSIONS: WRF occurs in nearly 30% of HFrEF patients without impacting clinical outcomes; HF specialists should be aware of these changes to avoid unnecessary discontinuation of sacubitril/valsartan therapy.
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Aminobutiratos/efeitos adversos , Antagonistas de Receptores de Angiotensina/efeitos adversos , Compostos de Bifenilo/efeitos adversos , Nefropatias , Valsartana/efeitos adversos , Aminobutiratos/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Combinação de Medicamentos , Taxa de Filtração Glomerular , Insuficiência Cardíaca/tratamento farmacológico , Hospitalização/estatística & dados numéricos , Humanos , Nefropatias/induzido quimicamente , Nefropatias/fisiopatologia , Estudos Retrospectivos , Valsartana/uso terapêuticoRESUMO
Transthoracic echocardiography is the primary non-invasive modality for the investigation of heart transplant recipients. It is a versatile tool that provides comprehensive information on cardiac structure and function. Echocardiography is also helpful in diagnosing primary graft dysfunction and evaluating the effectiveness of therapeutic approaches for this condition. In acute rejection, echocardiography is useful with suspected cellular or antibody-mediated rejection, with findings confirmed and quantified by endomyocardial biopsy. For identifying chronic rejection, ultrasound has a more significant role and, in some specific patients (e.g., patients with renal failure), it may offer a role comparable to coronary angiography to identify cardiac allograft vasculopathy. This review highlights the usefulness of echocardiography in evaluating normal graft function and its role in the management of heart transplant recipients.
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The usefulness of cardiopulmonary exercise test (CPET) in adult hypertrophic cardiomyopathy (HCM) patients is well-known, whereas its role in pediatric HCM patients has not yet been explored. The present study investigates possible insights from a CPET assessment in a cohort of pediatric HCM outpatients in terms of functional and prognostic assessment. Sixty consecutive pediatric HCM outpatients aged <18 years old were enrolled, each of them undergoing a full clinical assessment including a CPET; a group of 60 healthy subjects served as controls. A unique composite end-point of heart failure (HF) related and sudden cardiac death (SCD) or SCD-equivalent events was also explored. During a median follow-up of 53 months (25th-75th: 13-84 months), a total of 13 HF- and 7 SCD-related first events were collected. Compared to controls, HCM patients showed an impaired functional capacity with most of them showing peak oxygen uptake (pVO2) values of <80% of the predicted, clearly discrepant with functional New York Heart Association class assessment. The composite end-point occurred more frequently in patients with the worst CPETs' profiles. At the univariate analysis, pVO2% was the variable with the strongest association with adverse events at follow-up (C-index = 0.72, p = 0.025) and a cut-off value equal to 60% was the most accurate in identifying those patients at the highest risk. In a pediatric HCM subset, the CPET assessment allows a true functional capacity estimation and it might be helpful in identifying early those patients at high risk of events.
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Cardiomiopatia Hipertrófica/diagnóstico , Cardiomiopatia Hipertrófica/fisiopatologia , Teste de Esforço , Adolescente , Criança , Feminino , Humanos , Masculino , Consumo de Oxigênio , Modelos de Riscos Proporcionais , Curva ROC , Análise de SobrevidaRESUMO
The end stage or burned-out phase is an uncommon but challenging clinical evolution of hypertrophic cardiomyopathy (HCM). The management of end-stage HCM is empirically based on the use of drugs approved for heart failure with reduced ejection fraction; however, cardiac transplantation often represents the best option to improve survival. In our case, we describe the use of sacubitril/valsartan as a 'bridge to transplant' in a patient with end-stage HCM. After introducing the drug, enhancements in functional capacity, a reduction in natriuretic peptides and an increase in left ventricular ejection fraction occurred. Given their improved volume of oxygen consumption (VO2) peak and hemodynamic parameters, our patient was left off the waiting list for cardiac transplant and continues to be regularly followed-up with every 3 months.
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Cardiomiopatia Hipertrófica , Insuficiência Cardíaca , Aminobutiratos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Compostos de Bifenilo , Cardiomiopatia Hipertrófica/tratamento farmacológico , Combinação de Medicamentos , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Volume Sistólico , Valsartana , Função Ventricular EsquerdaRESUMO
BACKGROUND: right ventricle-pulmonary artery (RV-PA) coupling assessed by measuring the tricuspid anular plane systolic excursion (TAPSE)/pulmonary artery systolic pressure (PASP) ratio has been recently proposed as an early marker of right ventricular dysfunction in patients with heart failure with a reduced ejection fraction (HFrEF). METHODS: As the effects of sacubitril/valsartan therapy on RV-PA coupling remain unknown, this study aimed to analyse the effect of this drug on TAPSE/PASP in patients with HFrEF. We retrospectively analysed all outpatients with HFrEF referred to our unit between October 2016 and July 2018. RESULTS: At the 1-year follow-up, sacubitril/valsartan therapy was associated with a significant improvement in TAPSE (18.26 ± 3.7 vs. 19.6 ± 4.2 mm, p < 0.01), PASP (38.3 ± 15.7 vs. 33.7 ± 13.6, p < 0.05), and RV-PA coupling (0.57 ± 0.25 vs. 0.68 ± 0.30 p < 0.01). These improvements persisted at the 2-year follow-up. In the multivariable analysis, the improvement in the RV-PA coupling was independent of the left ventricular remodelling. CONCLUSIONS: in patients with HFrEF, sacubitril/valsartan improved the RV-PA coupling; however, further trials are necessary to evaluate the role of sacubitril/valsartan in the treatment of right ventricle (RV) dysfunction either associated or not associated with left ventricular dysfunction.
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Clinical trials have shown the benefits of ß-blockers therapy in patients with heart failure reduced ejection fraction. These benefits include improved survival and a reduced need for hospitalization. Cardiac resynchronization therapy has emerged as an essential device-based therapy for symptomatic patients with heart failure reduced ejection fraction despite optimal pharmacologic treatment. The extent to which ß-blockers are being utilized in patients receiving cardiac resynchronization therapy is not well known. In this study, we evaluate the possibility of increasing ß-blockers doses in an unselected cohort of heart failure reduced ejection patients after cardiac resynchronization therapy capable defibrillator system implantation and the correlation between ß-blockers treatments and clinical outcome. Methods and results: Patients with heart failure reduced ejection fraction in ß-blockers therapy that underwent cardiac resynchronization therapy capable defibrillator system implantation between July 2008, and December 2016 were enrolled in the study. The ß-blockers dose was determined at the time of discharge and during follow-up. Cardiovascular mortality, hospitalization for worsening heart failure or arrhythmic storm and appropriate intervention of the device, were recorded. The study cohort included 480 patients, 289 patients (60.3%) had ß-blockers doses equal to the dose before CRT (Group 1), 191 patients (39.7%) had higher ß-blockers doses than those before the CRT implant (Group 2). Comparing the two groups, Group 2 have lower cardiovascular mortality, heart failure-related hospitalization, and arrhythmic events than Group 1. Conclusion: After initiating CRT, ß-blockers could be safely up-titrated at higher doses with the reduction in mortality, heart failure-related hospitalization, and arrhythmic events.
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BACKGROUND: A blunted heart rate (HR) response is associated with an impaired peak oxygen uptake (pVO2), a powerful outcome predictor in hypertrophic cardiomyopathy (HCM). The present multicenter study sought to determine the prognostic role for exercise-induced HR response in HCM. METHODS: A total of 681 consecutive HCM outpatients on optimized treatment were recruited. The heart failure (HF) end-point was death due to HF, cardiac transplantation, NYHA III-IV class progression, HF worsening leading to hospitalization and severe functional deterioration leading to septal reduction. The sudden cardiac death (SCD) end-point included SCD, aborted SCD and appropriate implantable cardioverter defibrillator discharges. RESULTS: During a median follow-up of 4.2â¯years (25-75th centile: 3.9-5.2), 81 patients reached the HF and 23 the SCD end-point. Covariates with independent effects on the HF end-point were left atrial diameter, left ventricular ejection fraction, maximal left ventricular outflow tract gradient and exercise cardiac power (ECPâ¯=â¯pVO2∗systolic blood pressure) (C-Indexâ¯=â¯0.807) whereas the HCM Risk-SCD score and the ECP remained associated with the SCD end-point (C-Indexâ¯=â¯0.674). When the VO2-derived variables were not pursued, peak HR (pHR) re-entered in the multivariate HF model (C-Indexâ¯=â¯0.777) and, marginally, in the SCD model (C-indexâ¯=â¯0.656). A pHRâ¯=â¯70% of the maximum predicted resulted as the best cut-off value in predicting the HF-related events. CONCLUSIONS: The cardiopulmonary exercise test is pivotal in the HCM management, however the pHR remains a meaningful alternative parameter. A pHRâ¯<â¯70% identified a HCM population at high risk of HF-related events, thus calling for a reappraisal of the chronotropic incompetence threshold in HCM.
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Cardiomiopatia Hipertrófica/diagnóstico , Cardiomiopatia Hipertrófica/fisiopatologia , Frequência Cardíaca/fisiologia , Adulto , Cardiomiopatia Hipertrófica/mortalidade , Estudos de Coortes , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/prevenção & controle , Feminino , Seguimentos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
INTRODUCTION: Hypertriglyceridemia (triglycerides ≥200 mg/dL) is a major cardiovascular risk factor. Despite the high incidence of this condition in the Italian population, epidemiological information remains limited. AIM: To analyze a large database of clinical charts from general practitioners in the Rome area of Italy. METHODS: In this study, the DATAMEG database of patients treated in the Rome area between 2000 and 2015 was analyzed. The database was searched for information on (1) all patients diagnosed with hypertriglyceridemia, (2) all prescriptions for the treatment of hypertriglyceridemia, and (3) all patients who had an acute myocardial infarction. RESULTS: The overall prevalence of hypertriglyceridemia was 4.4% (3647/82,595). Among patients followed from January 1, 2015 onwards, 2786/55,345 (5.0%) were diagnosed with hypertriglyceridemia. Of these, 418 (15.0%) received at least one prescription of triglyceride-lowering treatment. Over the same period, 1653 patients had at least three measurements of triglycerides ≥200 mg/dL, with only 357 (21.6%) receiving at least one prescription of triglyceride-lowering drugs in the year following the last measurement. Furthermore, 513 patients had at least one measurement of ≥500 mg/dL. Of these, only 246 (48.0%) received at least one prescription of triglyceride-lowering drugs in the year following the last measurement. In total, 3485 patients had an acute myocardial infarction (prevalence, 4.3%) in 2015. Of these, only 288 (8.3%) received at least one prescription of triglyceride-lowering drugs in the year following this event. CONCLUSION: These findings confirmed a pattern of inadequate treatment of hypertriglyceridemia in the Rome area.
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Hipertrigliceridemia/epidemiologia , Infarto do Miocárdio/epidemiologia , Biomarcadores/sangue , Bases de Dados Factuais , Medicina Geral , Humanos , Hipertrigliceridemia/sangue , Hipertrigliceridemia/diagnóstico , Hipertrigliceridemia/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/prevenção & controle , Prevalência , Medição de Risco , Fatores de Risco , Cidade de Roma/epidemiologia , Fatores de Tempo , Triglicerídeos/sangueRESUMO
Pediatric heart failure represents an important cause of morbidity and mortality in childhood. Currently, there are well-established guidelines for the management of heart failure in the adult population, but an equivalent consensus in children is lacking. In the clinical setting, ensuring an accurate diagnosis and defining etiology is essential to optimal treatment. Diuretics and angiotensin-converting enzyme inhibition are the first-line therapies, whereas beta-blockers and devices for electric therapy are less used in children than in adults. In the end-stage disease, heart transplantation is the best choice of treatment, while a left ventricular assist device can be used as a bridge to transplantation (due to the difficulties in finding organ donors), recovery (in the case of myocarditis), or destination therapy (for patients with systemic disease).