Are Sodium-Glucose Cotransporter-2 Inhibitors the Cherry on Top of Cardio-Oncology Care?

The increasing aging of the population combined with improvements in cancer detection and care has significantly improved the survival and quality of life of cancer patients. These benefits are hampered by the increase of cardiovascular diseases being heart failure the most frequent manifestation of cardiotoxicity and becoming the major cause of morbidity and mortality among cancer survivor. Current strategies to prevent cardiotoxicity involves different approaches such as optimal management of CV risk factors, use of statins and/or neurohormonal medications, and, in some cases, even the use of chelating agents. As a class, SGLT2-i have revolutionized the therapeutic horizon of HF patients independently of their ejection fraction or glycemic status. There is an abundance of data from translational and observational clinical studies supporting a potential beneficial role of SGLT2-i in mitigating the cardiotoxic effects of cancer patients receiving anthracyclines. These findings underscore the need for more robust clinical trials to investigate the effect on cardiovascular outcomes of the prophylactic SGLT2-i treatment in patients undergoing cancer treatment.

Sodium-Glucose Cotransporter 2 Inhibitors in Frail Patients with Heart Failure: Clinical Experience of a Heart Failure Unit.

OBJECTIVE: The objective of this study was to determine the difference in tolerance for sodium glucose cotransporter 2 inhibitors between patients with heart failure classified as frail according to the FRAIL questionnaire, compared to those with heart failure without frailty. METHODS: A prospective cohort study was performed between 2021 and 2022 that included patients with heart failure at a heart failure unit in Bogotá who were being treated with a sodium glucose cotransporter 2 inhibitor. Clinical and laboratory data were collected during an initial visit and 12-48 weeks after that. The FRAIL questionnaire was applied to all participants through a phone call or during the follow-up visit. The primary outcome was the adverse effect rate and as a secondary outcome we compared the estimated glomerular filtration rate change between frail and non-frail patients. RESULTS: One hundred and twelve patients were included in the final analysis. Frail patients had a more than twice increased risk of having adverse effects (95% confidence interval 1.5-3.9). Age was also a risk factor for the appearance of these.  The estimated glomerular filtration rate decrease was inversely correlated with the age, left ventricular ejection fraction, and renal function before the use of sodium glucose cotransporter 2 inhibitors. CONCLUSIONS: When prescribing in heart failure, it is important to remember that frail patients are more likely to have adverse effects with the use of sodium glucose cotransporter 2 inhibitors, of which the most common are those related to osmotic diuresis. Nonetheless, these do not appear to increase the risk of discontinuation or abandonment of therapy in this population.

A Case of Wild-type Cardiac Transthyretin Amyloidosis Diagnosed by Non-invasive Methods.

INTRODUCTION: Transthyretin amyloid cardiomyopathy was considered a rare pathology. However, recent studies show a significant prevalence in patients with degenerative aortic stenosis and heart failure with preserved ejection fraction. CASE PRESENTATION: An 85-year-old woman presented with a four-month history of pain in the rib cage with a history of diffuse large B-cell lymphoma of the oral cavity, essential thrombocytosis and dyslipidemia. She had no significant family history. A transthoracic echocardiogram showed degenerative aortic stenosis and normal systolic function with preserved left ventricular ejection fraction of 70%. Bone-avid tracer cardiac scintigraphy with technetium-99m-labeled hydroxymethylene diphosphonate with SPECT-CT documented grade two myocardial uptake according to the Perugini scale. MRI evidenced late patchy enhancement in the myocardium associated with diffuse subendocardial enhancement. Laboratory tests showed the absence of mutation in the transthyretin (TTR) gene, serum and urine immunofixation electrophoresis (IFE) negative for monoclonal protein and serum-free light chain (sFLC) assay with a normal kappa/lambda (K/L) ratio. All these findings were compatible with a non-invasive diagnosis of wild-type cardiac amyloidosis. CONCLUSION: The accepted criteria for the definitive non-invasive diagnosis of amyloid cardiomyopathy are based on myocardial uptake by scintigraphy (with SPECT), serum and urine immunofixation electrophoresis, serum-free light chain assay and suggestive findings on echocardiography and/or MRI. Genetic testing should differentiate between ATTRv (v for variant) and ATTRwt (wt for wild type) forms.

Impact on clinical events and healthcare costs of adding telemedicine to multidisciplinary disease management programmes for heart failure: Results of a randomized controlled trial.

BACKGROUND: The role of telemedicine in the management of patients with chronic heart failure (HF) has not been fully elucidated. We hypothesized that multidisciplinary comprehensive HF care could achieve better results when it is delivered using telemedicine. METHODS AND RESULTS: In this study, 178 eligible patients with HF were randomized to either structured follow-up on the basis of face-to-face encounters (control group, 97 patients) or delivering health care using telemedicine (81 patients). Telemedicine included daily signs and symptoms based on telemonitoring and structured follow-up by means of video or audio-conference. The primary end-point was non-fatal HF events after six months of follow-up. The median age of the patients was 77 years, 41% were female, and 25% were frail patients. The hazard ratio for the primary end-point was 0.35 (95% confidence interval (CI), 0.20-0.59; p-value < 0.001) in favour of telemedicine. HF readmission (hazard ratio 0.39 (0.19-0.77); p-value=0.007) and cardiovascular readmission (hazard ratio 0.43 (0.23-0.80); p-value=0.008) were also reduced in the telemedicine group. Mortality was similar in both groups (telemedicine: 6.2% vs control: 12.4%, p-value > 0.05). The telemedicine group experienced a significant mean net reduction in direct hospital costs of €3546 per patient per six months of follow-up. CONCLUSIONS: Among patients managed in the setting of a comprehensive HF programme, the addition of telemedicine may result in better outcomes and reduction of costs.

Experiencia con sacubitril/valsartán en una clínica de falla cardiaca / Experience with sacubitril/valsartan in a heart failure clinic

Resumen Objetivo: describir las características y el comportamiento clínico de pacientes tratados con sacubitril/valsartán en una clínica de falla cardiaca de un hospital de alta complejidad. Métodos: se analizaron en retrospectiva 56 pacientes en manejo con sacubitril/valsartán, entre enero de 2017 y mayo de 2018. A los tres meses de inicio del tratamiento, 87% de los pacientes fueron evaluados. Se determinaron cambios en clase funcional, fracción de eyección ventricular izquierda (FEVI) y presión arterial sistólica y diastólica. Se registraron reingresos hospitalarios por falla cardiaca, mortalidad cardiovascular y eventos adversos asociados a la medicación. Resultados: la edad promedio fue 71,3 años; 51,7% correspondían al sexo masculino, 73% tenía etiología isquémica, 35% clase funcional NYHA II y 60% NYHA III antes de iniciar el tratamiento con sacubitril/valsartán. Al finalizar el seguimiento, 57% mejoró su clase funcional y 81,7% se encontraba en clase funcional NYHA II (IC95%, -0,52 a-0,18; p=0,0002). Hubo mejoría significativa en los valores de FEVI respecto a los basales (IC95%, 4,27 a 11,86; p=0,0002). Se observó una disminución significativa de la presión arterial tanto sistólica como diastólica (p<0,01). Un paciente presentó muerte súbita (2%) y uno hospitalización por falla cardiaca (2%). Ningún paciente descontinuó la terapia por efectos adversos. Conclusión: sacubitril/valsartán es una terapia útil en pacientes con falla cardiaca sintomática y FEVI reducida. La población evaluada tenía un perfil demográfico y clínico semejante al del ensayo clínico PARADIGM-HF, lo cual sugiere que los desenlaces clínicos son similares en la población colombiana.

Abstract Objective: The aim of this study is to describe the characteristics and clinical behaviour of patients treated with sacubitril/valsartan in a heart failure clinic of a high complexity hospital. Methods: A retrospective analysis was performed on a total of 56 patients on treatment with sacubitril/valsartan, between January 2017 and May 2018. At three months from the start of the treatment, 87% of the patients were evaluated. Changes were observed in functional class, left ventricular ejection fraction (LVEF), and systolic and diastolic arterial pressure. A record was made of hospital re-admissions due to heart failure, cardiovascular mortality, and adverse events associated with the medication. Results: The mean age of the patients was 71.3 years, of which 51.7% were male. An ischaemic origin was found in 73%. NYHA II and NYHA III functional class was observed 35% and 60%, respectively, before starting the treatment with sacubitril/valsartan. At the end of follow-up, 57% improved their functional class, and 81.7% were found to be in NYHA II functional class (95% CI; -0.52 to -0.18:=0.0002). There was a significant improvement in the LVEF values compared to baseline (95% CI; 4.27 to 11.86; P=0.0002). A significant decrease was observed in both systolic and diastolic blood pressure (P<0.01). There was sudden death in one (2%) patient and one (2%) patient admitted due to heart failure. None of the patients stopped the therapy due to secondary effects. Conclusion: Sacubitril/valsartan is a useful therapy in patients with symptomatic heart failure and a decreased LVEF. The population evaluated had a demographic and similar clinical signs and symptoms to the PARADIGM-HF clinical trial, which suggests that the clinical outcomes are similar in the Colombian population.

Evaluación de la fragilidad en la enfermedad cardiovascular: Un reto necesario / Assessment of frailty in cardiovascular disease: A necessary challenge

Resumen En el escenario clínico es cada vez más frecuente la atención de pacientes adultos mayores, lo cual es un desafío debido a la presencia de mayor comorbilidad y de condiciones o síndromes geriátricos (fragilidad, sarcopenia, caídas) que usualmente los acompañan. La fragilidad es un síndrome común en el paciente anciano, en quien existe una disminución de la reserva fisiológica que genera vulnerabilidad frente a factores estresantes. Su prevalencia aumenta a la par con la expectativa de vida, y tiene un impacto significativo en la salud pública ya que estudios han demostrado que se asocia con mayores tasas de hospitalización, desenlaces adversos quirúrgicos, mortalidad y costos para los sistemas de salud. Se hace revisión actualizada de la relación existente entre la fragilidad y enfermedad cardiovascular. El conocimiento sobre fragilidad sirve como guía para tomar decisiones y como objeto de investigación de un segmento de una población con gran crecimiento.

Abstract The care of elderly patients is becoming increasingly more common in the clinical setting. This presents a challenge due to there being increased comorbidity and the presence of geriatric conditions or syndromes (frailty, sarcopenia, falls) that usually accompany them. Frailty is a common syndrome in the elderly patient, in which there is a decrease in physiological reserve that can lead to vulnerability to stress factors. Its prevalence increases on a par with life expectancy, and has a significant impact on public health since studies have demonstrated that it is associated with higher hospital admission rates, adverse surgical outcomes, mortality, and costs for the health systems. An update review has been made on the existing relationship between frailty and cardiovascular disease. Knowledge about frailty will serve as a guide to make decisions and as an objective in the investigation of an increasingly growing segment of the population.

Differences in neurohormonal activity partially explain the obesity paradox in patients with heart failure: The role of sympathetic activation.

BACKGROUND: Obese patients with chronic Heart Failure (HF) have better outcome than their lean counterparts, although little is known about the pathophysiology of this obesity paradox. Our aim was to evaluate the hypothesis that patients with chronic HF and obesity (defined as body mass index (BMI)≥30kg/m(2)), may have an attenuated neurohormonal activation in comparison with non-obese patients. METHODS AND RESULTS: The present study is the post-hoc analysis of a cohort of 742 chronic HF patients from a single-center study evaluating sympathetic activation by measuring baseline levels of norepinephrine (NE). Obesity was present in 33% of patients. Higher BMI and obesity were significantly associated with lower NE levels in multivariable linear regression models adjusted for covariates (p<0.001). Addition to NE in multivariate Cox proportional hazard models attenuated the prognostic impact of BMI in terms of outcomes. Finally, when we explored the prognosis impact of raised NE levels (>70th percentile) carrying out a separate analysis in obese and non-obese patients we found that in both groups NE remained a significant independent predictor of poorer outcomes, despite the lower NE levels in patients with chronic HF and obesity: all-cause mortality hazard ratio=2.37 (95% confidence interval, 1.14-4.94) and hazard ratio=1.59 (95% confidence interval, 1.05-2.4) in obese and non-obese respectively; and cardiovascular mortality hazard ratio=3.08 (95% confidence interval, 1.05-9.01) in obese patients and hazard ratio=2.08 (95% confidence interval, 1.42-3.05) in non-obese patients. CONCLUSION: Patients with chronic HF and obesity have significantly lower sympathetic activation. This finding may partially explain the obesity paradox described in chronic HF patients.

Cuidado paliativo en falla cardiaca / Palliative care in heart failure

Resumen La falla cardiaca avanzada se caracteriza por un compromiso circulatorio clínicamente significativo que requiere opciones de manejo avanzadas como el trasplante cardiaco, la inotropía intravenosa continua o intermitente, la asistencia ventricular o la terapia paliativa. El paciente con falla cardiaca avanzada no candidato a trasplante o asistencias ventriculares, es terminal y hace parte de un grupo heterogéneo con una condición clínica que fluctúa, con síntomas que condicionan el deterioro de la calidad de vida, y finalmente la muerte. El cuidado paliativo hace parte de las opciones de tratamiento avanzado cuyo objetivo principal es el control de los síntomas en el paciente con enfermedad avanzada, la planificación de los cuidados del final de la vida y los que permiten tener una muerte digna. No es una estrategia reservada para el paciente agónico. Es importante tener una comunicación asertiva con el paciente y su familia, y contar con las herramientas adecuadas para tomar decisiones y comunicarlas. Este documento presenta de forma concreta y práctica la forma de identificar y manejar el paciente con falla cardiaca terminal, con estrategias farmacológicas y no farmacológicas para el control de los síntomas más comunes en esta etapa de la enfermedad, así como de los aspectos relevantes sobre el manejo de dispositivos y conceptos sobre la transición del cuidado y la sedación paliativa.

Abstract Advanced heart failure is characterised by a clinically significant circulatory involvement that requires advances management options such as cardiac transplantation, continuous or intermittent inotropic infusions, ventricular assist devices or palliative therapy. Patients with advanced heart failure who are not candidate for a transplant or ventricular assist devices are terminal and belong to an heterogeneous group with a fluctuating clinical condition, with symptoms that impart their quality of life and eventually cause death. Palliative care is a part of the advanced therapy options whose main goal is to control symptoms in the patient with advanced disease, to plan care in the final stage of life and to allow for a dignified death. It is not a strategy limited to terminal patients. It is important to maintain assertive communication with the patient and their relatives, and to have the necessary tools to make and communicate decisions. This document presents in a concrete and practical manner the way of identifying and managing patients with terminal heart failure, with pharmacological and non-pharmacological strategies to control the most common symptoms at this stage of the disease, as well as therelevant aspects on handling devices and concepts about care transition and palliative sedation.

La hiponatremia en la insuficiencia cardíaca: fisiopatología y enfoque farmacológico / Hyponatremia in heart failure: Physiopathology and pharmacological approach

La hiponatremia es un factor asociado a mal pronóstico bien conocido en pacientes que presentan insuficiencia cardíaca (IC) crónica. Los mecanismos que conectan la hiponatremia con el mal pronóstico no están plenamente dilucidados, y posiblemente se hallen en relación a la presencia de un manejo inadecuado del agua libre y a la activación neurohormonal típica de los pacientes con IC crónica y que a su vez se asocian a peor evolución en ellos. Posiblemente, el grado de retención de agua libre sea superior a la proporción de retención de sodio en estos pacientes lo que, al menos parcialmente, explicaría la presencia de hiponatremia en la IC crónica. Hay diversas estrategias de tratamiento disponibles de la hiponatremia en la IC, aunque ninguna de ellas se ha mostrado demasiado eficaz, y que incluyen desde la restricción hídrica a la administración de tratamientos agresivos con diuréticos, pasando por la perfusión de suero salino hipertónico. Recientemente, el antagonismo de la vasopresina mediante los antagonistas de los receptores de la vasopresina ha conllevado una nueva vía de tratamiento de la hiponatremia en estos pacientes mediante la estimulación de la acuaresis. Hay diversos agentes disponibles, aunque aún no se ha establecido de forma plena el posible impacto de estos nuevos fármacos en la morbimortalidad de los pacientes que presentan hiponatremia en el contexto de la IC crónica (AU)

Hyponatremia is a well-known adverse prognostic factor in patients with chronic heart failure. The mechanisms linking hyponatremia with poor outcomes in these patients are not well understood and may be related to the presence of the abnormal management of water and neurohormonal activation seen in patients with chronic heart failure, which in turn are associated with a worse prognosis. Possibly, free-water retention exceeds the degree of sodium retention in chronic heart failure, which could partially explain the hyponatremia found in these patients. There are several therapeutic strategies for the management of hyponatremia in patients with chronic heart failure, including fluid restriction, high-dose diuretic administration and infusion of hypertonic saline, but none has been proven to be very effective. Recently, vasopressin antagonism through vasopressin receptor antagonists has opened up a new way of treating hyponatremia in these patients by enhancing aquaresis. Several agents are available but their possible impact on morbidity and mortality in patients with hyponatremia and chronic heart failure requires elucidation (AU)