Warfarin and Aspirin Versus Warfarin Alone in Patients With HeartMate 3 Left Ventricular Assist Device: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: HeartMate 3 (HM3), a fully magnetically levitated ventricular assist device (LVAD), has been associated with reduced thromboembolic events compared to HeartMate II. However, bleeding events remained significant. Among patients undergoing HM3 implantation, the standard antithrombotic regimen comprises both warfarin and aspirin (ASA), but there is a lack of evidence on the optimum antithrombotic therapy. We performed a systematic review and meta-analysis assessing the impact of combined ASA and warfarin therapy compared to warfarin alone on the incidence of non-surgical bleeding events in patients with HM3 LVAD. METHODS: MEDLINE, Embase, and Cochrane databases were searched for randomized controlled trials (RCTs) and observational studies comparing warfarin alone with warfarin combined with ASA in patients with HM3 LVAD. Binary endpoints were analyzed using computed risk ratios (RRs) with 95% confidence intervals (CIs). A random-effect model was applied for all endpoints. RESULTS: Five studies (one RCT and four observational) encompassing 869 patients were included, with 424 (48.8%) prescribed warfarin alone, and 662 (76.2%) being male. Compared with the combined anticoagulation regimen, warfarin alone significantly reduced non-surgical bleeding (RR 0.30; 95% CI 0.09-0.95; p = 0.04) and gastrointestinal bleeding (RR 0.26; 95% CI 0.12-0.58; p < 0.001). There was no statistically significant difference between the groups for all-cause mortality (RR 1.02; 95% CI 0.45-2.32; p = 0.963). CONCLUSIONS: Our findings indicate that the use of warfarin alone for anticoagulation in HM3 patients is associated with a reduced risk of bleeding events when compared to the combined therapy with ASA.

Sodium-glucose cotransporter-2 inhibitors in acute myocardial infarction: a systematic review and meta-analysis of randomized controlled trials.

We aimed to assess the efficacy and safety of sodium-glucose cotransporter-2 inhibitors (SGLT2i) versus placebo, initiated within the hospitalization period, in addition to habitual treatment, for treating adult patients with confirmed acute myocardial infarction (AMI). We also conducted subgroup analysis by diabetes mellitus (DM) status and type of AMI. We systematically searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCTs). The primary outcome was hospitalization for heart failure (HF). The secondary outcomes were all-cause death, cardiovascular death, and serious adverse events (AEs). We pooled risk ratios (RR) with a 95% confidence interval (CI) for binary outcomes. The between-study variance was assessed using tau2 statistics. We included five RCTs, encompassing 11,211 patients. SGLT2i significantly reduced the risk of hospitalization for HF compared to placebo (RR 0.73; 95% CI [0.61, 0.88]). However, the risk of all-cause death (RR 1.05; 95% CI [0.78, 1.41]) and cardiovascular death (RR 1.04; 95% CI [0.84, 1.29]) was similar between the groups, as well as the risk of serious AEs (RR 1.01; 95% CI [0.90, 1.14]). In the subgroup analysis by DM status and type of AMI, there were no significant subgroup differences for the outcomes of hospitalization for HF and all-cause death. In patients with AMI, treatment with SGLT2i is safe and significantly reduces the risk of hospitalization for HF, but it has no impact on all-cause death and cardiovascular death compared to placebo.

[Cardiogenic shock assisted with venoarterial extracorporeal membrane oxygenation: experience of an Argentine institution]. / Shock cardiogénico asistido con oxigenación por membrana extracorpórea venoarterial: Experiencia de una institución argentina.

INTRODUCTION: Cardiogenic shock carries a mortality rate of 40-50%. In cases that progress unfavorably despite pharmacological treatment, ventricular assist devices such as venoarterial extracorporeal membrane oxygenation play a prominent role. Although two recent controlled clinical trials have been published, the primary source of information remains observational studies, which are notably scarce in Argentina. MATERIALS AND METHODS: A retrospective cohort study was conducted, including patients from January 2012 to April 2023 with refractory cardiogenic shock supported by venoarterial extracorporeal membrane oxygenation. Their baseline characteristics, clinical course, and acute versus chronic presentation were analyzed. RESULTS: 61 patients were supported with venoarterial extracorporeal membrane oxygenation for refractory cardiogenic shock. 51% were supported as a bridge to cardiac transplantation. 84% of the patients were in INTERMACS grades 1 or 2 at the time of support initiation. The assisted patients had a survival rate of 44%, similar to results reported by the Extracorporeal Life Support Organization. The most frequent complications were renal replacement therapy (46%) and sepsis (38%). Patients with acute presentation had better survival outcomes. DISCUSSION: Venoarterial extracorporeal membrane oxygenation support is a valid therapy for refractory cardiogenic shock unresponsive to conventional treatments. Experience in Argentina is limited. In this study, survival rates align with international registries, highlighting the therapy's significant value in our institution. Acute presentation of cardiogenic shock correlates with improved survival outcomes.

Introducción: El shock cardiogénico presenta una mortalidad del 40-50%. En los casos que evoluciona desfavorablemente a pesar del tratamiento farmacológico, los dispositivos de asistencia ventricular, como la oxigenación por membrana extracorpórea venoarterial, adquieren un papel protagónico. Si bien recientemente se publicaron dos ensayos clínicos controlados, la mayor fuente de información proviene de estudios observacionales, siendo estos especialmente escasos en Argentina. Materiales y métodos: Se realizó un estudio de cohorte retrospectivo, que incluyó pacientes desde enero del 2012 a abril del 2023 con shock cardiogénico refractario asistidos con oxigenación por membrana extracorpórea venoarterial. Se analizaron sus características basales, evolución y forma de presentación en agudo versus crónica. Resultados: Sesenta y un pacientes fueron asistidos con oxigenación por membrana extracorpórea venoarterial por shock cardiogénico refractario. Al 51% se los asistió como puente a trasplante cardíaco. El 84% de los asistidos se encontraban en grados INTERMACS 1 o 2 al momento de la asistencia. Los pacientes asistidos presentaron una sobrevida del 44%, similar a los resultados publicados por Extracorporeal Life Support Organization. Las complicaciones más frecuentes fueron la terapia de reemplazo renal (46%) y la sepsis (38%). Los pacientes con presentación aguda tuvieron mayor sobrevida. Discusión: La asistencia con oxigenación por membrana extracorpórea venoarterial es una terapia válida para el shock cardiogénico refractario a terapias convencionales. La experiencia en Argentina es escasa. En el presente estudio la sobrevida se asemeja a registros internacionales, siendo esta terapia de gran valor en nuestra institución. La forma de presentación aguda del shock cardiogénico expone una mayor sobrevida.

[Prevalence and evolution of left ventricular insufficiency in patients undergoing severe aortic insufficiency]. / Prevalencia y evolución de la insuficiencia ventricular izquierda en pacientes con insuficiencia aórtica grave.

INTRODUCTION: Aortic insufficiency (AR) evolves during follow-up with dilation of the left chambers and eventually with deterioration of the ejection fraction (EF). Treatment as well as evolution of EF after the procedure remains uncertain. The objective of the following work was to establish the prevalence of ventricular dysfunction and evaluate the evolution of EF at 6 months in patients with aortic valve replacement (AVR) due to AR. MATERIALS AND METHODS: A retrospective, descriptive, observational, single-center cohort study was carried out from 1/1/2012 to 12/31/2022. All patients undergoing AVR for severe AR were included. The proportion of patients operated on with EF less than 55%, and their evolution within the first 6 months, were calculated and its evolution within the first 6 months according to the protocol. Recovery was defined as an increase of 10% compared to the pre-surgical EF. RESULTS: Of 685 patients, 74 had severe AR of which. 4.6% (n= 32) underwent AVR with EF< 55%. The median presurgical EF was 50% [IQR 43.6-53]. At 6 months, 45% (n=11) met recovery criteria with a median EF of 64% (compared to 52% in the group without recovery, p=0.01). In-hospital mortality was 6.2%; 24 of the 32 patients completed follow-up. DISCUSSION: The percentage of patients with AR who undergo surgery with left ventricular dysfunction is approximately 50%. In our study 45% had an improvement in ejection fraction at 6 months.

Introducción: La insuficiencia aórtica (IAO) evoluciona con dilatación de cavidades izquierdas y ocasionalmente con deterioro de la fracción de eyección (FEY). El tratamiento, así como la evolución de la FEY luego del procedimiento, continúan siendo inciertos. El objetivo del trabajo fue establecer la prevalencia de disfunción ventricular y evaluar la evolución de la FEY a 6 meses en paciente con reemplazo valvular aórtico (RVA) por IAO. Materiales y métodos: Se realizó un estudio de cohorte retrospectivo, observacional descriptivo, unicéntrico, desde el 1/1/2012 al 31/12/2022. Se incluyeron todos los pacientes sometidos a RVA por IAO grave. Se calculó la proporción de pacientes operados con FEY menor a 55%, y su evolución dentro de los primeros 6 meses de acuerdo al protocolo. Se definió recuperación como un aumento de 10% con respecto a la FEY prequirúrgica. Resultados: Un total de 685 pacientes recibieron un RVA, 74 de ellos por IAO grave. Tuvieron FEY prequirúrgica < 55% 32 de 74, el 43%. La mediana de FEY prequirúrgica de este grupo fue 50% [RIC 43.6-53]. La mortalidad intrahospitalaria fue del 6.2% y completaron el seguimiento 24 de los 32 pacientes. A los 6 meses, el 45% (n=11) cumplió criterios de recuperación (mediana de FEY de 64% vs. 52% en el grupo sin recuperación). Discusión: El porcentaje de pacientes con IAO que se operan con disfunción ventricular izquierda es de aproximadamente el 50%. En nuestro estudio un 45% tuvo mejoría de la FEY a los 6 meses.

Non-invasive telemonitoring programs for patients with chronic heart failure: A systematic review and meta-analysis of randomized controlled trials.

AIMS: To assess whether telemonitoring improves outcomes in patients with chronic heart failure. METHODS AND RESULTS: A literature search was conducted on studies of randomized controlled trials involving non-invasive telemonitoring and heart failure using Medline, Embase, and Cochrane Library. The primary outcomes were all-cause mortality, all-cause hospitalization, and hospitalization for heart failure. Secondary outcomes were length of stay, health-related quality of life as assessed by validated questionnaires, healthcare costs and cost-effectiveness, and self-care behaviors. We performed a meta-analysis using a random effects model for the primary outcomes. The effect measure was odds ratio with corresponding 95% confidence interval, and heterogeneity among studies was assessed using the Higgins I2 value. We screened 212 references, and 34 randomized controlled trials were included in this review. A total of 16179 participants with heart failure were included. Non-invasive telemonitoring reduced all-cause mortality by 18% (OR 0.82, 95% CI 0.71 to 0.95; participants = 15,211; studies = 28; I2 = 34%; GRADE: moderate-quality evidence) and heart failure hospitalization by 20% (OR 0.80, 95% CI 0.69 to 0.94; participants = 7491; studies = 18; I2 = 31%; GRADE: moderate-quality evidence). Non-invasive telemonitoring didn't demonstrate significant benefit on all-cause hospitalization (OR 0.93, 95% CI 0.82 to 1.05; participants = 11,565; studies = 25; I2 = 49%). CONCLUSION: Telemonitoring programs in patients with heart failure were associated with a reduction in all-cause mortality and heart failure hospitalization without harmful events.

Comparison in the adult congenital heart disease severity classification of ACC/AHA and ESC guidelines in a 3,459 Mexican population.

Background: Latin American registries of clinical and demographic profiles of ACHD are scarce. International guidelines classify disease complexity with different approaches. With these two regards, a registry was carried out to examine factors associated with mortality and to compare severity classifications in our population. Methods and results: Cross-sectional study conducted on ACHD between 2018 and 2022 to evaluate clinical and demographic characteristics and to assess the agreement between the 2020 ESC Guidelines and 2018 AHA/ACC Guidelines for the Management of Adults with Congenital Heart Disease using the kappa method. Binomial logistic regression models were used to examine correlates of mortality. 3459 patients were included [56 % women, median age 34 years (IQR 24-50)]; 83.41 % were alive and 4.11 % died. The subjects had the following characteristics: 74.18 % were in NYHA I FC, 87.30 % had SVEF ≥50 %, 18.42 % developed arrhythmias, 58.92 % were surgically repaired, 7.05 % received palliative management, and 0.03 % were in heart transplant protocol. The agreement between ESC and AHA/ACC complexity classifications was low (43.29 %) in moderate ACHD, and high (83.10 %) in severe disease. Mortality was higher in patients with NYHA III-IV FC, arrhythmias and under palliative care. Conclusion: This study found that ESC and AHA/ACC complexity classifications have limited concordance in categorizing moderate complexity CHD. Reparative procedures had lower mortality odds than palliative care.

Prospective registry of heart failure with preserved ejection fraction in México: EDIFICE-Mx.

Background and aims: Heart failure with preserved ejection fraction (HFpEF) is an increasingly common clinical syndrome, estimated to constitute approximately 50 % of all heart failure (HF) cases. Nonetheless, registries from specific geographic areas, as Latin America, are lacking. The present study aims to report the underlying causes, comorbidities, treatment patterns and outcomes of patients with HFpEF in a large cardiovascular center in Mexico City. Methods: The present is a prospective, longitudinal, observational study, including female and male patients over 18 years of age, who presented to the emergency department, coronary care unit or outpatient department of the National Institute of Cardiology Ignacio Chavez in Mexico City with HFpEF. Patients were classified according to different phenotypes and current literature. The primary outcome was the composite total HFpEF hospitalization and all-cause mortality. Results: Within a median follow-up of 472 (IQR 425-518) days, total mortality was 14.56 %, with 10.68 % attributed to cardiovascular causes. HF hospitalization was 7.77 %. Atrial fibrillation showed a notable association with outcomes (adjusted HR 2.87, P = 0.028). Beta-blocker showed a non-significant trend towards benefit, while mineralocorticoid receptor antagonists (MRA) significantly influenced outcomes (adjusted HR 3.30, P = 0.018). The primary composite endpoint occurred in 19.42 % of patients, with no significant difference among phenotypes (P = 0.536). Conclusions: We observed a substantial comorbidity burden impacting quality of life, as indicated by KCCQ scores. There was a high incidence of hard endpoints, including cardiovascular death and hospitalizations, alongside significant variability in treatment utilization. Future research should focus on elucidating individual healthcare trajectories in HFpEF patients and promoting wider adoption of evidence-based therapies.

SGLT2 Inhibitors in Cardiovascular Medicine: Panacea or Pandora's Box?

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are antidiabetic agents that effectively lower blood glucose levels in patients with Type 2 Diabetes Mellitus (T2DM). Beyond their glycemic control properties, SGLT2 inhibitors have demonstrated significant cardiovascular benefits, including reductions in major adverse cardiovascular events. However, the limitations of the pivotal trials investigating these outcomes have not been fully explored. This letter aims to critically assess the major randomized clinical trials that evaluated the cardiovascular effects of SGLT2 inhibitors, highlighting both their strengths and limitations.

Association of potassium disorders with the mode of death and etiology in patients with chronic heart failure: the INCOR-HF study.

Observational studies suggest a U-shaped association between serum potassium (K⁺) levels and mortality in patients with chronic heart failure (CHF). However, the mode of death in patients with HF and K⁺ disorders remains speculative. To investigate the association between potassium disorders and the mode of death in patients with CHF. A retrospective cohort of 10,378 CHF outpatients was analyzed over an average of 3.28 ± 2.5 years. Kaplan-Meier method, Cox proportional hazards regression models, Poisson regression models adjusting for confounders, and e-value determination (e' > 1.6) were used to observe associations between potassium disorders and outcomes. Chagas etiology (p < 0.01) and triple HF therapy (p < 0.01) were associated with hyperkalemia. Atrial fibrillation was associated with hypokalemia (p < 0.01). Chronic kidney disease (CKD) (p < 0.01) and diabetes (p = 0.03) were associated with both. Hypertension was inversely related to hyperkalemia (p < 0.01); age was inversely related to hypokalemia. Associations with mortality were significant for Chagas (p < 0.01, e-value 2.16), stroke (p < 0.01, e-value 1.85), hypokalemia (p = 0.02, e-value 1.94), severe hyperkalemia (p = 0.08, e-value 1.93), and CKD (p < 0.01, e-value > 1.63). Decompensated HF or cardiogenic shock was the cause of death in 54% of patients with normokalemia, 67.8% with hypokalemia, 44.9% with mild hyperkalemia, 57.8% with moderate hyperkalemia, and 69% with severe hyperkalemia. Most patients with hypokalemia and severe hyperkalemia died from decompensated HF (p = 0.007). Data suggest hypokalemia and severe hyperkalemia, along with Chagas and CKD, are associated with death. Unexpectedly, progressive HF was the most frequent mode of death rather than arrhythmias. Further studies are needed to confirm these findings and explore the underlying mechanisms.

Estudio URUguayo de intervención educativa potenciada en pacientes anticoagulados con WArfarina en una unidad de Insuficiencia cardíaca (URUWAI)

Introducción: La warfarina es uno de los medicamentos más prescritos en el tratamiento y prevención de enfermedades tromboembólicas. El beneficio en la prevención de eventos trombóticos y en la reducción de la mortalidad está ampliamente documentado. Sin embargo, los aspectos relacionados con la seguridad han limitado su uso. El acompañamiento de pacientes, con especial atención en la información y educación sobre sus patologías, hábitos saludables, cumplimiento de tratamientos y comprensión de riesgos, es fundamental para conseguir buenos resultados, disminuyendo la morbi-mortalidad y las internaciones. La información respecto al perfil de seguridad y la calidad de la anticoagulación bajo un programa de intervención educativa es escasa en Uruguay. El objetivo de este estudio es analizar el efecto de un plan de intervención educativa potenciada con atención farmacéutica (IEPAF), sobre la calidad de anticoagulación con warfarina de pacientes ambulatorios de la unidad multidisciplinaria de insuficiencia cardíaca (UMIC), comparar la efectividad y seguridad del tratamiento, y evaluar la utilidad del score SAMeTT2R2. Metodología: Ensayo clínico randomizado. Se reclutaron pacientes en seguimiento en la UMIC tratados con warfarina y se randomizaron a control médico habitual vs control médico con ajustes de dosis según un protocolo establecido, más IEPAF. Resultados: Luego de 24 meses de seguimiento, ambos grupos mantuvieron buen nivel de anticoagulación, con tiempo en rango terapéutico (TTR) de 83,15% y 83,80% para grupo control e intervención respectivamente. La intervención educativa potenciada y el protocolo de ajuste de dosis de warfarina, aportó un resultado equiparable al seguimiento convencional de la anticoagulación. Conclusiones: La IEPAF promovió un resultado equiparable en seguridad, efectividad y adherencia con respecto al seguimiento convencional. Ambos grupos lograron un excelente nivel de anticoagulación evaluado por TTR. Del análisis post hoc surge una asociación estadísticamente significativa de los valores de SAMeTT2R2 4 y 6, con la aparición de eventos, con un riesgo relativo 5 veces mayor para el sexo femenino.

Introduction: Warfarin is one of the most prescribed drugs for the treatment and prevention of thromboembolic diseases. The benefit of the prevention of thrombotic events and the reduction of mortality is widely documented. However, security issues have limited its use. Monitoring patients, with special attention to information and education about their pathologies, healthy habits, compliance with treatment, and understanding of risks, is essential to achieve good results, reducing morbidity, mortality and hospitalizations. Information regarding anticoagulation's safety profile and quality under an educational intervention program is scarce in Uruguay. The objective of this study is to analyze the effect of an enhanced educational intervention plan with pharmaceutical care (IEPAF), on the quality of anticoagulation with warfarin in outpatients in the multidisciplinary heart failure unit (UMIC), and to compare the effectiveness and safety of treatment, and to evaluate the usefulness of the SAMeTT2R2 score. Methodology: Randomized clinical trial. Patients under follow-up in UMIC treated with warfarin were recruited and randomized to usual medical control vs medical control with dose adjustments according to an established protocol, plus enhanced educational intervention IEPAF. Results: After 24 months of follow-up, both groups maintained a good level of anticoagulation, with time in therapeutic range (TTR) of 83,15% and 83,80% for the control and intervention groups, respectively. The enhanced educational intervention and the warfarin dose adjustment protocol provided results comparable to conventional anticoagulation monitoring. Conclusions: The IEPAF with pharmaceutical care promoted a comparable result in safety, effectiveness, and adherence concerning conventional follow-up. Both groups achieved an excellent level of anticoagulation as assessed by TTR. From the post hoc analysis, a statistically significant association of SAMeTT2R2 values 4 and 6 emerges with events, with a relative risk 5 times greater for the female sex.

Introdução: A warfarina é um dos medicamentos mais prescritos para o tratamento e prevenção de doenças tromboembólicas. O benefício na prevenção de eventos trombóticos e na redução da mortalidade está amplamente documentado. No entanto, problemas de segurança limitaram seu uso. O acompanhamento dos pacientes, com atenção especial à informação e educação sobre suas patologias, hábitos saudáveis, adesão ao tratamento e compreensão dos riscos, é fundamental para o alcance de bons resultados, reduzindo a morbimortalidade e internações. Informações sobre o perfil de segurança e a qualidade da anticoagulação em um programa de intervenção educacional são escassas no Uruguai. O objetivo deste estudo é analisar o efeito de um plano de intervenção educacional aprimorado com assistência farmacêutica (IEPAF) , na qualidade da anticoagulação com warfarina em pacientes ambulatoriais na unidade multidisciplinar de insuficiência cardíaca (UMIC), e comparar a eficácia e segurança de tratamento e avaliar a utilidade do escore SAMeTT2R2. Metodologia: Ensaio clínico randomizado. Pacientes em acompanhamento em UMIC em tratamento com warfarina foram recrutados e randomizados para controle médico usual versus controle médico com ajustes de dose de acordo com protocolo estabelecido, além IEPAF. Resultados: Após 24 meses de seguimento, ambos os grupos mantiveram um bom nível de anticoagulação, com tempo na faixa terapêutica (TTR) de 83,15% e 83,80% para os grupos controle e intervenção, respectivamente. A intervenção educacional aprimorada e o protocolo de ajuste de dose de warfarina forneceram resultados comparáveis ​​ao monitoramento de anticoagulação convencional. Conclusões: O IEPAF com assistência farmacêutica promoveu resultado comparável em segurança, eficácia e adesão em relação ao acompanhamento convencional. Ambos os grupos alcançaram um excelente nível de anticoagulação avaliado pela TTR. Da análise post hoc emerge uma associação estatisticamente significativa dos valores 4 e 6 do SAMeTT2R2 com a ocorrência de eventos, com risco relativo 5 vezes maior para o sexo feminino.

Spinal cord stimulation in a patient with an implantable cardioverter defibrillator for managing chronic chest pain: a case report and literature review.

The simultaneous use of spinal cord stimulation (SCS) and an implantable cardioverter-defibrillator (ICD) is safe and effective in selected patients with refractory chest pain. Our case highlights successful pain management with SCS without compromising ICD function. Careful patient selection, low device settings, and ongoing monitoring are crucial for achieving optimal outcomes.

What is this article about? Spinal cord stimulators are used to treat pain that won't go away. However, some patients also have implantable electronic devices, which makes them worry that the two devices may not work well together. This article describes a case in which both devices were used and presents a literature review regarding the possible interactions between these two devices.What were the results? Spinal cord stimulation is a safe and efficient treatment for persistent refractory pain in patients using implantable cardiac electronic devices.What do the results means? These results suggest that spinal cord stimulation is a safe and effective treatment for chronic refractory pain in patients using cardiac implantable electronic devices.

CO-CREATION-HF protocol: clinical trial to evaluate the impact of a comprehensive and hybrid cardiac rehabilitation model on patients with heart failure.

Introduction: Comprehensive, hybrid cardiac rehabilitation (CR) models have been scantly investigated in heart failure (HF) populations, particularly in low-resource settings. CO-CREATION-HF aims to evaluate the effectiveness of such a model compared to supervised exercise alone. Methods and analysis: A 2 parallel-arm, multi-center randomized clinical superiority trial will be conducted with blinded outcome assessment. 152 HF patients (NYHA class II or III) will be recruited consecutively, and randomly assigned using permuted blocks; allocation will be concealed. The 12-week intervention will include evaluation, medical and nurse management, aerobic interval training, resistance exercise training, psychosocial support, and education. These will initially be delivered in a center, transitioning to home in 4 stages. Controls will receive similar management, but face-to-face continuous aerobic exercise sessions and resistance exercises. The main outcomes are cardiorespiratory fitness (VO2 max), functional capacity (m from 6 MWT), and quality of life (Minnesota Living with Heart Failure Questionnaire). Program adherence and completion, NT-proBNP, functioning, all-cause and HF-specific mortality and hospitalization, muscle strength, adverse events and cost will be secondary outcomes. These will be measured at baseline, end of intervention, and 12-month follow-up. The sample size was calculated considering 90% power, a significance level of 5%, a between-group difference equivalent to 1/2 MET, and a 10% potential loss to follow-up. Intention-to-treat analysis will be considered. Between-group differences will be assessed using Student's t-tests or Z-tests along with 95% confidence intervals, and the rate ratio will be computed to compare mortality. Ethics and dissemination: The study protocol and the Informed Consent form were approved by Ethical Committees at the Universidad de La Frontera (No. 081-23) and each center participating. Research findings will be disseminated to the scientific community and will be shared with relevant stakeholder groups and policy-makers. Finally, investigators shall reach HF patients via various dissemination channels such as social media. Clinical Trial Registration: clinicaltrials.gov, identifier (NCT06313684).

[Diabetic cardiomyopathy: a focus on sodium-glucose cotransporter type 2 inhibitors]. / Miocardiopatía diabética: un enfoque en los inhibidores del cotransportador sodio-glucosa tipo 2.

Diabetic cardiomyopathy (DCM) is a complication of type 2 diabetes mellitus (T2DM) capable of progressing to the development of symptomatic heart failure (HF), independently of traditional risk factors for it, such as coronary artery disease and hypertension. There is no specific treatment for DCM; however, sodium-glucose cotransporter 2 inhibitors (SGLT2i) are hypoglycemic drugs that act on SGLT2 channels, inhibiting glucose reabsorption in the kidney. In addition, they have cardioprotective effects, which is why their mechanisms at the cardiac level have been studied. According to the results of preclinical studies, SGLT2i act by interfering in the pathophysiology of DCM. Their main effects are: improvement in diastolic function and left ventricular ejection fraction (LVEF), attenuation in the progress of cardiac fibrosis, reduction of oxidative stress and proinflammatory markers. The clinical trials in humans specifically with DCM that have been carried out are limited; however, randomized clinical trials in patients with HF have shown benefits with SGLT2i, regardless of glycemic control in the reduction of hospitalization for HF and mortality from cardiovascular causes. In summary, SGLT2i suggest a treatment in DCM due to their cardiovascular benefits, in preclinical and clinical models of DCM and in the glycemic control of T2DM.

La miocardiopatía diabética (MCD) es una complicación de la diabetes mellitus tipo 2 (DM2) que es capaz de evolucionar hasta desarrollar insuficiencia cardiaca (IC) sintomática, independientemente de los factores de riesgo tradicionales para esta, como la enfermedad de las arterias coronarias y la hipertensión. No hay un tratamiento específico para la MCD; sin embargo, los inhibidores del cotransportador sodio-glucosa tipo 2 (iSGLT2) son fármacos hipoglucemiantes que actúan en los canales SGLT2 e inhiben la reabsorción de glucosa en el riñón; además, tienen efectos cardioprotectores, por lo que sus mecanismos a nivel cardiaco se han estudiado. De acuerdo con resultados de estudios preclínicos, los iSGLT2 actúan al interferir en la fisiopatología de la MCD. Sus principales efectos son: mejoramiento en la función diastólica y la fracción de eyección del ventrículo izquierdo (FEVI), atenuación en el progreso de la fibrosis cardiaca, reducción del estrés oxidativo y marcadores proinflamatorios. Los ensayos clínicos en humanos que se han realizado específicamente con MCD son limitados; no obstante, ensayos clínicos aleatorizados en pacientes portadores de IC han evidenciado beneficios con iSGLT2, independientemente del control glucémico en la reducción de hospitalización por IC y mortalidad por causas cardiovasculares. Resumiendo, los iSGLT2 nos sugieren un tratamiento en la MCD por sus beneficios cardiovasculares, en modelos preclínicos y clínicos de MCD y en el control glucémico de la DM2.

Prognostic value of the diagnosis of anemia in patients with heart failure: an analysis based on the Colombian heart failure registry (RECOLFACA).

BACKGROUND: Anemia represents a commonly reported comorbidity in patients diagnosed with heart failure (HF), related with a higher risk of unfavorable outcomes such as recurrent hospitalizations and mortality. There is a lack of evidence in Latin America regarding this topic. Our aim was to evaluate the prognostic value of the diagnosis of anemia in patients from the Colombian Heart Failure Registry (RECOLFACA). METHODS: RECOLFACA registry included adult ambulatory patients with HF in 60 medical centers in Colombia during 2017-2019. Baseline characteristics of patients diagnosed with anemia and those without anemia were compared. The main outcome was all-cause mortality. A Cox proportional hazards regression model was used to evaluate the factors linked to the main outcome in patients with anemia. A statistically significant p-value was < 0.05. RESULTS: From the 2528 patients included in RECOLFACA, 2409 had at least one available hemoglobin value, and 726 (30.1%) corresponded to a diagnosis of anemia. Patients with anemia were significantly older, and had a higher prevalence of comorbidities, especially hypertension, type 2 diabetes, and chronic kidney disease (CKD). Patients without anemia had significantly lower mortality rate of 0.30 per 1000 person-years (95% CI 0.26-0.35), compared to patients diagnosed with anemia who had a mortality rate of 0.42 per 1000 person-years (95% CI 0.26-0.98) (p < 0.001). Lastly, the multivariate model results showed that the presence of an anemia diagnosis was associated with a significantly greater risk of mortality (HR 1.48; 95% CI 1.06, 2.05, p < 0.001). CONCLUSIONS: Anemia represents a highly prevalent comorbidity in patients with HF in Colombia and is also related with higher mortality in ambulatory patients during follow-up period. Our results highlight the relevance of anemia in the pathophysiology of HF. Nevertheless, due to its observational nature, out study results must be validated and further explored in future studies to elucidate the potential underlying mechanisms of this association.

Reliability, internal consistency, and validity of the World Health Organization disability assessment schedule (WHODAS) 2.0 among adults with heart failure.

BACKGROUND: Heart failure (HF) imposes significant disability. The World Health Organization Disability Assessment Schedule (WHODAS) 2.0 is a generic instrument that measures disability. Although it has been used in HF, no previous study has investigated its measurement properties in this group. OBJECTIVE: To assess the test-retest reliability, internal consistency, convergent, and discriminant validity of WHODAS 2.0 in individuals with HF. METHODS: We conducted a cross-sectional study that included individuals with HF treated at the outpatient cardiology center. Data included sociodemographic and clinical (e.g., New York Heart Association - NYHA) characteristics, estimated functional capacity (Duke Activity Status Index - DASI), quality of life (Minnesota Living with Heart Failure Questionnaire - MLHFQ), and disability (the WHODAS 2.0 36-item version). We assessed associations, using Pearson's correlation coefficient or the Kruskal-Wallis test, between the WHODAS 2.0 scores and the MLHFQ, DASI, and NYHA. The WHODAS 2.0 results were collected again seven days after the initial assessment for reliability (intraclass correlation coefficient - ICC). RESULTS: Participants were 100 people with HF (M age = 57.8 ± 14 years, 57 % men), of whom 84 % were literate. The WHODAS 2.0 was reliable (ICC = 0.789) and had good internal consistency (Cronbach's alpha >0.7 in all domains). Convergent validity was observed through moderate correlations with DASI and MLHFQ and discriminant validity with statistically different results according to NYHA classes. CONCLUSION: WHODAS 2.0 is a reliable, consistent, and valid instrument for measuring disability in individuals with HF. Further research is needed to evaluate other properties, such as its responsiveness to interventions.

Value-based health care in heart failure: Quality of life and cost analysis.

OBJECTIVES: To measure Quality of Life (QoL) and costs of Heart Failure (HF) outpatients in Brazil as an introduction to the Value-Based Health Care (VBHC) concept. MATERIALS AND METHODS: Cross-sectional study, patients with HF, with ejection fraction <50%, were recruited from three hospitals in Brazil. Two QoL (36-Item Short Form Survey [SF-36] and Minnesota Living with Heart Failure Questionnaire [MLHFQ]) and two anxiety/depression questionnaires were applied. SF-36 scores were stratified by domains. Treatment costs were calculated using the Time-Driven Activity-Based Costing (TDABC) method. Results were stratified by NYHA functional class and sex. RESULTS: From October 2018 to January 2021, 198 patients were recruited, and the median MLHFQ (49.5 [IQR 21.0, 69.0]) and SF-36 scores demonstrated poor QoL, worse at higher NYHA classes. A third of patients had moderate/severe depression and anxiety symptoms, and women had higher anxiety scores. Mean costs of outpatient follow-up were US$ 215 ± 238 for NYHA I patients, US$ 296 ± 399 for NYHA II and US$ 667 ± 1012 for NYHA III/IV. Lab/exam costs represented 30% of the costs in NYHA I, and 74% in NYHA III/IV (US$ 63.26 vs. US$ 491.05). CONCLUSION: Patients with HF in Brazil have poor QoL and high treatment costs; both worsen as the NYHA classification increases. It seems that HF has a greater impact on the mental health of women. Costs increase mostly related to lab/exams. Accurate and crossed information about QoL and costs is essential to drive care and reimbursement strategies based on value.

Role of NLRP3 Inflammasome in Heart Failure Patients Undergoing Cardiac Surgery as a Potential Determinant of Postoperative Atrial Fibrillation and Remodeling: Is SGLT2 Cotransporter Inhibition an Alternative for Cardioprotection?

In heart failure (HF) patients undergoing cardiac surgery, an increased activity of mechanisms related to cardiac remodeling may determine a higher risk of postoperative atrial fibrillation (POAF). Given that atrial fibrillation (AF) has a negative impact on the course and management of HF, including the need for anticoagulation therapy, identifying the factors associated with AF occurrence after cardiac surgery is crucial for the prognosis of these patients. POAF is thought to occur when various clinical and biochemical triggers act on susceptible cardiac tissue (first hit), with oxidative stress and inflammation during cardiopulmonary bypass (CPB) surgery being potential contributing factors (second hit). However, the molecular mechanisms involved in these processes remain poorly characterized. Recent research has shown that patients who later develop POAF often have pre-existing abnormalities in calcium handling and activation of NLRP3-inflammasome signaling in their atrial cardiomyocytes. These molecular changes may make cardiomyocytes more susceptible to spontaneous Ca2+-releases and subsequent arrhythmias, particularly when exposed to inflammatory mediators. Additionally, some clinical studies have linked POAF with elevated preoperative inflammatory markers, but there is a need for further research in order to better understand the impact of CPB surgery on local and systemic inflammation. This knowledge would make it possible to determine whether patients susceptible to POAF have pre-existing inflammatory conditions or cellular electrophysiological factors that make them more prone to developing AF and cardiac remodeling. In this context, the NLRP3 inflammasome, expressed in cardiomyocytes and cardiac fibroblasts, has been identified as playing a key role in the development of HF and AF, making patients with pre-existing HF with reduced ejection fraction (HFrEF) the focus of several clinical studies with interventions that act at this level. On the other hand, HFpEF has been linked to metabolic and non-ischemic risk factors, but more research is needed to better characterize the myocardial remodeling events associated with HFpEF. Therefore, since ventricular remodeling may differ between HFrEF and HFpEF, it is necessary to perform studies in both groups of patients due to their pathophysiological variations. Clinical evidence has shown that pharmacological therapies that are effective for HFrEF may not provide the same anti-remodeling benefits in HFpEF patients, particularly compared to traditional adrenergic and renin-angiotensin-aldosterone system inhibitors. On the other hand, there is growing interest in medications with pleiotropic or antioxidant/anti-inflammatory effects, such as sodium-glucose cotransporter 2 inhibitors (SGLT-2is). These drugs may offer anti-remodeling effects in both HFrEF and HFpEF by inhibiting pro-inflammatory, pro-oxidant, and NLRP3 signaling pathways and their mediators. The anti-inflammatory, antioxidant, and anti-remodeling effects of SGLT-2 i have progressively expanded from HFrEF and HFpEF to other forms of cardiac remodeling. However, these advances in research have not yet encompassed POAF despite its associations with inflammation, oxidative stress, and remodeling. Currently, the direct or indirect effects of NLRP3-dependent pathway inhibition on the occurrence of POAF have not been clinically assessed. However, given that NLRP3 pathway inhibition may also indirectly affect other pathways, such as inhibition of NF-kappaB or inhibition of matrix synthesis, which are strongly linked to POAF and cardiac remodeling, it is reasonable to hypothesize that this type of intervention could play a role in preventing these events.

What's new in cardiac amyloidosis? Pharmacological treatment, physical activity, and care of patients with transthyretin cardiac amyloidosis.

Awareness, proper diagnosis and treatment of cardiac amyloidosis have increased, but there are still several unmet needs that have to be addressed for the optimal care of the disease. In this comprehensive review, we describe current and future treatments for both hereditary and wild-type TTR cardiac amyloidosis and also review lifestyle, including current challenges and opportunities for specific dietary concerns and exercise sports for these patients.