Optimal Heart Failure Therapy Research Articles

UNPREDICTABLE IDENTIFICATION OF A TITIN MUTATION IN A YOUNG PATIENT PRESENTING WITH INFLAMMATORY CARDIOMYOPATHY

Abstract Case Presentation A 23 years old patient, affected by type 1 diabetes, presented with fever, dyspnea and bilateral peripheral edemas. In the last week he received antibiotic treatment for a persistent dry cough and sore throat, and became symptomatic for exertional dyspnea from three days. His mother died at the age of 40 for sudden cardiac death. Blood pressure and oxygen saturation were normal: the ECG showed sinus tachycardia with symmetric negative T waves in all precordial leads. High sensitivity troponin T was 0.01 mcg/L (normal value < 0.014 mcg/L). All remaining blood tests were normal, except for CRP that was slightly elevated. His echocardiogram revealed left ventricular (LV) remodelling and dilation, severely reduced LV ejection fraction (LVEF 20%) with global hypokinesia, more pronounced at the level of the anterior wall, interventricular septum and apex and a dilated right ventricle (RV) with reduced systolic function. Cardiac magnetic resonance (CMR) confirmed severe biventricular disfunction (LVEF 19%; RVEF 23%) and showed a small area of subepicardial inferior junctional late gadolinium enhancement (LGE). The patient underwent an endomyocardial biopsy that showed a lymphocytic virus–negative myocarditis. Given his known type 1 diabetes, steroid treatment was not considered and anakinra was started. The patient was discharged after two weeks with a slight amelioration of the LV function (LVEF 27%), on optimal heart failure therapy and anakinra. At six months he was in NYHA class II and CMR showed slight reduction in LV dimensions and improvement of the LV and RV function (LVEF 39%; RVEF 45%), with no changes in the LGE pattern. A genetic test was performed and revealed two titin gene mutations, both categorized as likely pathogenic (TTN c.[11831T>A]; c.[72510_72517delGACAAATG]), responsible for a genetic form of dilated cardiomyopathy. Conclusion The present case suggests that in young patients presenting with clinical or histological diagnosis of myocarditis, genetic testing for cardiomyopathies should be considered especially in presence of a positive family history for sudden death or an incomplete recovery of the LV function at follow–up. Identification of a gene mutation in these patients allows a more tailored risk stratification of the index case and a proper management of the entire family.

Long-Term Treatment With Sacubitril/Valsartan in Japanese Patients With Chronic Heart Failure and Reduced Ejection Fraction - Open-Label Extension of the PARALLEL-HF Study.

The PARALLEL-HF study assessed the efficacy and safety of sacubitril/valsartan vs. enalapril in Japanese patients with chronic heart failure with reduced ejection fraction (HFrEF). This open-label extension (OLE) assessed long-term safety with sacubitril/valsartan.Methods and Results: This study enrolled 150 patients who received sacubitril/valsartan 50 or 100 mg, b.i.d., in addition to optimal background heart failure (HF) therapy. A dose level of sacubitril/valsartan 200 mg, b.i.d., was targeted by Week 8. At OLE baseline, higher concentrations of B-type natriuretic peptide (BNP) and urine cGMP, and lower concentrations of N-terminal pro B-type natriuretic peptide (NT-proBNP), were observed in the sacubitril/valsartan core group (patients who received sacubitril/valsartan in both the core and extension study) than in the enalapril core group (patients who received enalapril in the core study and were then transitioned to sacubitril/valsartan). The mean exposure to study drug was 98.9%. There was no trend of worsening of HF at Month 12. No obvious changes in cardiac biomarkers were observed, whereas BNP and urine cGMP increased and NT-proBNP decreased in the enalapril core group, which was evident at Weeks 2-4 and sustained to Month 12. Long-term sacubitril/valsartan at doses up to 200 mg, b.i.d., has a positive risk-benefit profile; it was safe and well tolerated in Japanese patients with chronic HFrEF.

Exploring the Prognostic Performance of MECKI Score in Heart Failure Patients with Non-Valvular Atrial Fibrillation Treated with Edoxaban.

Risk stratification in heart failure (HF) is essential for clinical and therapeutic management. The Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score is a validated prognostic model for assessing cardiovascular risk in HF patients with reduced ejection fraction (HFrEF). From the validation of the score, the prevalence of HF patients treated with direct oral anticoagulants (DOACs), such as edoxaban, for non-valvular atrial fibrillation (NVAF) has been increasing in recent years. This study aims to evaluate the reliability of the MECKI score in HFrEF patients treated with edoxaban for NVAF. This study included consecutive outpatients with HF and NVAF treated with edoxaban (n = 83) who underwent a cardiopulmonary exercise test (CPET). They were matched by propensity score with a retrospective group of HFrEF patients with NVAF treated with vitamin K antagonists (VKAs) from the MECKI score registry (n = 844). The study endpoint was the risk of cardiovascular mortality, urgent heart transplantation, or Left Ventricle Assist Device (LVAD) implantation. Edoxaban patients were treated with a more optimized HF therapy and had different clinical characteristics, with a similar MECKI score. After propensity score, 77 patients treated with edoxaban were successfully matched with the MECKI-VKA control cohort. In both groups, MECKI accurately predicted the composite endpoint with similar area under the curves (AUC = 0.757 vs. 0.829 in the MECKI-VKA vs. edoxaban-treated group, respectively, p = 0.452). The two populations' survival appeared non-significantly different at the 2-year follow-up. this study confirms the prognostic accuracy of the MECKI score in HFrEF patients with NVAF treated with edoxaban, showing improved predictive power compared to VKA-treated patients.

Abstract 17139: Angiopoietin 2 Independently Predicts Heart Failure Hospitalization and is Beneficially Modified by GLP1RA: Results From the EXSCEL Trial

Background: Higher plasma concentrations of angiopoietin 2 (ANGPT2) are associated with higher risk for hospitalization for heart failure (HF) and death in univariate analyses. However, the independent association of this ANGPT2 after adjustment for clinical factors or clinically available biomarkers is not known. Methods: High throughput proteomic profiling was performed using the SomaLogic SomaScan platform in 5473 patients with type 2 diabetes enrolled in the EXSCEL clinical trial of the GLP1RA exenatide vs. placebo who had available biospecimens at baseline. The association between ANGPT2 with time-to-HF hospitalization, MACE, and death was assessed using univariable and multivariable Cox modeling, with adjustment for age, sex, HbA1c, NT-proBNP, hs-TnT, left ventricular ejection fraction, HF etiology and study treatment. These analyses were also performed in the subset of participants living with obesity (BMI >30 kg/m 2 ), and those with CKD (CrCl <60ml/min). Results: In 5473 EXSCEL trial participants included in this biomarker sub-study, 215 (3.9%) experienced a hospitalization for heart failure, 813 (14.9%) a MACE event and 528 (9.7%) died during a median follow-up of 3.2 years. Relative ANGPT2 concentration was significantly associated with HF hospitalization (aHR 1.70 [95% CI 1.39 to 2.08]), MACE (1.20 [1.07 to 1.35]), and death (aHR 1.21 [1.05 to 1.39]) in univariable and multivariable analyses, including after adjustment for NT-proBNP and TnT (Figure). Exenatide use resulted in significant changes from baseline in ANGPT2 concentrations (p interaction<0.001) (Figure). Conclusion: ANGPT2 is predictive of hospitalization for HF, MACE, and death independent of clinical factors including traditional biomarkers of NT-proBNP and TnT. ANGPT2 was beneficially modified by exenatide, a GLP1RA, suggesting a potential role for this biomarker in optimizing HF therapy.

Efficacy of dapagliflozin in the treatment of HFrEF with obstructive sleep apnea syndrome (DAHOS study): study protocol for a multicentric, prospective, randomized controlled clinical trial

BackgroundHeart failure with reduced ejection fraction (HFrEF) is associated with sleep dyspnea (SDB), which plays an adverse role in the pathophysiology of the condition. SDB management in HFrEF, however, remains controversial. HFrEF’s medical management has recently made significant progress with the discovery of new therapeutic avenues, namely sodia-glucose cotransporter-2 (SGLT-2) inhibitors, and better treatment of co-morbidities. Dapagliflozin, one of the SGLT-2 inhibitors, is a good candidate for correcting SDB of HFrEF patients because their known mechanisms of action are likely to counteract the pathophysiology of SDB in HFrEF.Methods/designThe trial is a 3-month, multicentric, prospective, randomized controlled clinical study. Patients (i.e., adults with left ventricular ejection fraction ≤ 40%, Apnoea–Hypopnoea Index ≥ 15) will be randomized to receive optimized heart failure therapy plus a standard dose of dapagliflozin, while the control group will receive only optimized heart failure therapy. Patients will be evaluated before and after 3 months (nocturnal ventilatory polygraphy, echocardiography, laboratory testing, and quality-of-life and SDB questionnaires). The primary outcome is the change in the Apnoea–Hypopnoea Index, before and after 3 months of treatment.Trial registrationwww.chictr.org.cn, ChiCTR2100049834. Registered 10 August 2021.

Relationship and outcomes between volume status, cardiac and renal dysfunction in patients with chronic heart failure

Abstract Funding Acknowledgements Type of funding sources: None. Background Right heart and renal dysfunction occurring due to volume fluid redistribution remain a front-line issue in the development of the syndrome of congestion in chronic heart failure (HF). Quantitative total blood volume (TBV) measurements and Speckle-tracking Echo (STE) provide complementary information on the myocardial function which allows for providing a more integrated assessment of clinical status and outcomes. Purpose We hypothesize adverse outcomes in patients with heart failure (HF) who have expansion of TBV, right ventricular (RV) and renal dysfunction. Methods This is a prospective study and a total of 66 participants NYHA class III&IV with chronic HF are enrolled from 2014-2022. TBV, right heart catheterization, TTE, TEE, and kidney function tests is performed. STE is calculated using TomTec software for all heart chambers. Patients is divided into 1-st group of the total participants, 2-nd group is patients adverse outcomes which are heart transplant (HT) or death, 3rd group is of alive patients. Simple, multivariable linear regression analyses is used to evaluate associations between TBV, cardiac and renal function. Statistical analyses is performed using JMP, BlueSky, and two-sided with P-values <0.05 considered to be statistically. Results Of 66 patients, the 1-st group has 66 patients, the 2nd group has 44 patients out of which deceased are 32 patients (48.4%), HT has 12 patients (18.1%), and the 3rd group has 22 patients (33.3%). In the 2nd group, out of the 44 patients, 35 (79.5%) patients have HFrEF, and 9 (20.4%) patients presented HFpEF. In the 3rd group out of 22 patients, 15 (68.2%) have HFrEF, and 7 (31.8%) patients have HFpEF. RV dimensions are significantly related to TBV in all groups of participants (Table 1). In the total patients, TBV is directly correlated to a moderate degree with EDSRV (r = 0.51, P < 0.001), ESSRV (r = 0.44, P < 0.001) and FAC (r = 0.40, P < 0.001). More significant moderate and strong relationships are observed in patients with adverse outcome between TVB and EDSRV (r = 0.54, P < 0.001), ESSRV (r = 0.65, P < 0.001) and FAC (r = 0.48, P < 0.001). In group 1, weak and direct association of TBV and RV GLS, FW LS, FW LSR, and RA reservoir strain. In the 2nd group, TBV directly correlated to a moderate degree with FW LS (r = 0.41, P = 0.005) and FW LSR (r = 0.43, P = 0.002). Similar relationships in the 2nd group are observed between TBV and renal function parameters (TBV and eGFR (r = 0.53, P < 0.001)). The direct and weak correlation obtained between TBV and BUN in both 1st and 2nd groups. In patients with adverse outcomes, TBV is directly proportional to LV Diastolic BP. Conclusion The association among intravascular volume and parameters of RV dilatation, myocardial and renal dysfunction in patients with chronic HF is associated with adverse outcomes. Understanding the impact of all these variables guide optimal and effective individualized HF management and therapy.

170 WHEN THE HEART GETS DRUNK

Abstract A 53-old male with arterial hypertension, obesity (BMI 32) and gout presented to our Emergency department symptomatic for dyspnea, complaining about reduced functional capacity (NYHA III), gain of weight e increased abdominal circumference. In the days after we discovered a history of potus (2 liter of wine/day). At a first physical examination we confirmed clinical features of heart failure with pulmonary congestion and ascites. The EKG showed atrial fibrillation, 80 bpm. An echocardiogram showed severely reduced ejection fraction (EF 23%) with diffuse hypokinesia, increased left ventricular mass, deeply increased volumes, with only slightly increased thickness, a mild moderate diastolic dysfunction. Also, the right ventricular was hypokinetic and dilatated. During the hospitalization the patient underwent coronary angiography, which showed no coronary lesion, e cardiac RMN with no pathological features in both T1 and T2 weighted sequences. No increased uptake of contrast in LGE sequences was evidenced. We started diuretic therapy and optimized heart failure therapy with clinical improvement. The management of anticoagulant therapy was difficult because of hepatic dysmetabolic cirrhosis (Child-Pugh Score 8, class B) with contraindication for DOACs treatment. Moreover the patient performed a gastroscopy, which evidenced an ulcerative gastro-duodenitis and erosive gastritis confirming the temporary DOACs contraindication. The patient was discharged in hemodynamic stability, with wearable defibrillator and was taken in charge by a multidisciplinary team. After the normalization of hepatic function the anticoagulation was no longer forbidden so after three weeks we proceeded to successful electrical cardioversion. An echocardiogram was performed after 6 months with almost completely recovery of systolic function (EF 62%) and a slightly reduction of chamber dilatations. The patient denied alcohol consumption throughout the period. This case demonstrates that alcoholic cardiopathy if it's diagnosed at the beginning can be partially reversible. This case presents a challenging clinical setting due to the frequent comorbidities requiring a multidisciplinary approach. Achieving a significant patient compliance is also crucial for long term lifestyle changes.

Abstract 12060: Ventricular Arterial Coupling - A Potential Biomarker in Children With Dilated Cardiomyopathy

Introduction: Ventriculo-arterial coupling (VAC) ratio (normal value: 0.6 - 1.2) is worse in children with dilated cardiomyopathy compared to controls and is associated with poor heart failure (HF) outcomes. It has not been studied in patients on oral HF medications. Our aim was to study VAC ratio as a measure of response to therapy and its ability to predict worse outcomes in this population. Methods: A retrospective study of DCM patients < 21 years on oral heart failure medications was conducted between 2010 and 2022 at the Children's Hospital At Montefiore. Medication data, NYHA functional class, and outcomes (mechanical circulatory support, transplantation, or death) were collected. A single observer analyzed the initial and the last echocardiograms on optimal HF therapy to calculate arterial elastance (EA), ventricular elastance (EES), and VAC ratio. Patients with and without outcomes were compared using chi-square & Mann Whitney tests, as appropriate. Results: Thirty-one patients (median age at diagnosis 1.25 (IQR 7.7) years) were followed for a median of 4.92 (IQR 11) years. There was a significant improvement in the VAC ratio (mean 1.85 vs 1.46, SEM 0.17, P=0.02) from diagnosis to the last follow-up with a median change of -13.5%. There was a statistically significant association between the percent change in VAC and change in the NYHA class (P=0.0001). Outcome events occurred in 7 patients; one required mechanical circulatory support, two died, and four underwent transplants. Patients with an outcome event had a worse VAC ratio both at diagnosis (P=0.03) and at the last follow-up (P=0.0001) and a worse NYHA class (P=0.001) at the last follow-up (Table). Conclusion: VAC is a potential biomarker for response to therapy and is associated with poor outcomes in pediatric DCM. It provides mechanistic insights into HF in this population.

Application of recommended therapies among patients with heart failure during the Syrian conflict: reality and barriers.

Lower socio-economic status may delay and even prevent the application of guideline-directed heart failure (HF) therapy for most patients. This study aims to evaluate the feasibility and possible difficulties facing the application of this treatment during the current Syrian conflict. A questionnaire on HF management and feasibility of recommended HF therapy was addressed to physicians practising cardiology in Syria. The questionnaire consisted of 30 questions and focused on the quality of HF management and awareness of recommended drug and device therapy for HF among physicians practising cardiology in Syria. A total of 228 physicians participated in the survey. Awareness of recommended medical and device therapy of HF was very high among participants (98% and 95%, respectively). The majority of participants (>75%) believe that more than half of HF patients do not receive optimal medical HF therapy. Ninety per cent of participants believe that <10% of patients with an appropriate indication for device therapy receive it. More than 75% of participants believe that the cost of medications, alone or in combination with other medical causes, represents the major problem facing the application of optimal HF medical therapy. More than 95% of participants reported that cost alone, or in combination with unavailability, is the primary reason why patients with appropriate indications are not offered device therapy. Despite the high level of awareness of recommended HF therapies among Syrian cardiologists, the majority of HF patients are still undertreated. Financial difficulties and lack of resources are the main causes of this problem.

Polypharmacy in Older Heart Failure Patients: a Multidisciplinary Approach.

We provide a review of considerations when applying principles of optimal pharmacotherapy to older adults with heart failure (HF), an analysis on the pivotal clinical trials focusing on applicability to older adults, and multi-disciplinary strategies to optimize the health of HF patients with polypharmacy. Polypharmacy is very common among patients with HF, due to medications for both HF and non-HF comorbidities. Definitions of polypharmacy were not developed specifically for older adults with HF and may need to be modified in order to meaningfully describe medication burden and promote appropriate medical therapy. This is because clinical practice guidelines for multi-drug HF regimens have unique considerations, given that they improve outcomes and symptoms of HF. Adults older than 65years are well represented in contemporary clinical trials for HF with preserved ejection fraction (HFpEF) and guideline directed medical therapy (GDMT) for HF with reduced ejection fraction (HFrEF). While these trials did not have significant heterogeneity in safety or efficacy across a broad age spectrum, some may have limited representation of adults ≥ 80years old, the sickest older adults, or those with decreased functional status. There is also a lack of data on the safety and efficacy of deprescribing HF medications, and deprescription in otherwise stable patients may lead to clinical destabilization or disease progression. There is therefore innate tension between the well-studied benefits of optimized HF therapy for older adults that must be weighed against the risks of polypharmacy and many unknowns that still exist. Given the strong evidence that optimized HF therapies confer symptomatic and mortality benefits for older adults, it is clear that polypharmacy in this context can be appropriate. A shift in paradigm is therefore needed when evaluating polypharmacy in patients with HF. Instead of assuming all polypharmacy is "good" or "bad," we propose a concerted move, using a multidisciplinary approach, to focus on the "appropriateness" of specific medications, in order to optimize HF medical therapy. Clinicians of all specialties caring for complex older adults with HF must consider goals of care, functional status, and new evidence-based therapies, in order to optimize this polypharmacy for older adults.

The impact of sleep disordered breathing on cardiac troponin in acutely decompensated heart failure

PurposeSleep disordered breathing in decompensated heart failure has physiological consequences (e.g., intermittent hypoxemia) that may predispose to subclinical myocardial injury, yet a temporal relationship between sleep apnea and troponin elevation has not been established.MethodsWe assessed the feasibility of performing respiratory polygraphy and measuring overnight high-sensitivity cardiac troponin T change in adults admitted to the hospital with acutely decompensated heart failure. Repeat sleep apnea tests (SATs) were performed to determine response to optimal medical heart failure therapy. Multivariable logistic regression was used to identify associations between absolute overnight troponin change and sleep apnea characteristics.ResultsAmong the 19 subjects with acutely decompensated heart failure, 92% of SATs demonstrated sleep disordered breathing (apnea–hypopnea index [AHI] > 5 events/h). For those with repeat SATs, AHI increased in 67% despite medical management of heart failure. Overnight troponin increase was associated with moderate to severe sleep apnea (vs. no to mild sleep apnea, odds ratio (OR = 18.4 [1.51–224.18]), central apnea index (OR = 1.11 [1.01–1.22]), and predominantly central sleep apnea (vs. obstructive, OR = 22.9 [1.29–406.32]).ConclusionsSleep apnea severity and a central apnea pattern may be associated with myocardial injury. Respiratory polygraphy with serial biomarker assessment is feasible in this population, and combining this approach with interventions (e.g., positive airway pressure) may help establish if a link exists between sleep apnea and subclinical myocardial injury.

A Comprehensive Approach to Managing Methamphetamine-Associated Cardiomyopathy.

Methamphetamines are illicit drugs of the amphetamine-type stimulant class that have been increasing in popularity, availability, and purity in recent decades. As a result, rates of methamphetamine-associated cardiomyopathy (MAC) are rising globally. MAC is associated with high rates of sudden cardiac arrest, late presentation, and poor outcomes. This review discusses the medical management of MAC, including anticipated challenges specific to methamphetamine users. Not only are patients with MAC more likely to present at a younger age and with multisystem disease than patients with cardiomyopathy of other etiologies, but there may also be significant behavioral, psychosocial, financial, and system-based challenges to providing the best medical care. An individualized treatment plan that emphasizes methamphetamine abstinence as the foundation of therapy, as well as introducing optimal heart failure therapy and providing multidisciplinary support is likely to result in optimal outcomes. Given the potential reversibility of MAC, institution of guideline-directed heart failure therapy and patient support for adherence to therapy and abstinence from methamphetamines should be energetically pursued.

Abstract 12050: Dapagliflozin Therapy is Associated With Improved Left and Right Ventricular Function in Chronic Heart Failure Patients With Reduced Ejection Fraction

Introduction: Although sodium-glucose transporter 2 inhibitors (SGLT2i) were shown to improve clinical outcomes of patients with heart failure with reduced ejection fraction (HFrEF), data on the effects of SGLT2i on myocardial function are scarce. Hypothesis: We evaluated the effects of dapagliflozin on left and right ventricular function in HFrEF patients. Methods: In a prospective sequential pilot clinical study we enrolled 14 HFrEF patients with NYHA II or III heart failure symptoms and LVEF&lt;40%. In Phase I, all patients were treated with optimized heart failure therapy including sacubitril/valsartan, beta blockers and spironolacton. After 3 months, dapagliflozin (10 mg qd) was added to the regimen and the patients were followed for another 3 months (Phase II). At baseline, 3- and 6- month follow-up we collected clinical, biochemical and echocardiographic data. Renal dysfuntion was defined as eGFR&lt;90 ml/min/1,73m 2 . Results: Of 14 patients, 10 (71%) were male; the average age was 57±16 years. Ishemic and non-ischemic heart failure was present in 3 (21%) and 11 (79%) of patients, respectively; 7 (50%) had renal dysfunction, 3 (21%) had diabetes and 6 (43%) had a history of hypertension. In Phase I we found no significant changes in LVEF (from 28±9% to 28±8%, P=0.91), left ventricular outflow tract VTI (LVOT VTI: from 12.8±3.6 cm to 13.3±5.3, P=0.80), or TAPSE (1.8±0.3 cm vs. 1.7±0.4 cm, P=0.62). Also, there were no significant changes in NYHA functional class (from 2.5±0.5 to 2.4±0.6, P=0.66), and NT-proBNP levels (from 1557±1745 pg/mL to 1677±1467 pg/mL, P=0.86). In contrast, in Phase II, we found a significant increase in LVEF (from 28±8% to 35±9%, P=0.02) and TAPSE (from 1.7±0.4 cm to 2.1±0.3 cm, P=0.04), and a trend of increase in LVOT VTI (from 13.3±5.3 cm to 16.7±3.4, P=0.07). In addition, after dapagliflozin therapy, we found a significant decrease in NYHA functional class (from 2.4±0.6 to 1.7±0.5, P=0.01) and NT-proBNP levels (from 1677±1467 pg/mL to 773±523, P=0.03). Conclusions: Dapagliflozin appears to improve echocardiographic parameters of left and right ventricular function in patients with HFrEF. Changes in heart function after dapagliflozin therapy occur in parallel with impovements in heart failure symptoms and levels of NTproBNP.

Heart and brain interactions in heart failure: Cognition, depression, anxiety, and related outcomes.

Cognitive impairment, anxiety and depression are common in heart failure (HF) patients and its evolution is not fully understood. To assess the cognitive status of HF patients over time, its relation to anxiety and depression, and its prognostic impact. Prospective, longitudinal, single center study including patients enrolled in a structured program for follow-up after hospital admission for HF decompensation. Cognitive function, anxiety/depression state, HF-related quality of life (QoL) were assessed before discharge and during follow-up (between 6th and 12th month) using Montreal Cognitive Assessment (MoCA), Hospital Anxiety and Depression Scale (HADS) and Kansas City Cardiomyopathy Questionnaire, respectively. HF related outcomes were all cause readmissions, HF readmissions and the composite endpoint of all-cause readmissions or death. 43 patients included (67±11.3 years, 69% male); followed-up for 8.2±2.1 months. 25.6% had an abnormal MoCA score that remained stable during follow-up (22.6±4.2 vs. 22.2±5.5; p=NS). MoCA score <22 at discharge conferred a sixfold greater risk of HF readmission [HR=6.42 (1.26-32.61); p=0.025], also predicting all-cause readmissions [HR=4.00 (1.15-13.95); p=0.03] and death or all-cause readmissions [HR=4.63 (1.37-15.67); p=0.014]. Patients with higher MoCA score showed a greater ability to deal with their disease (p=0.038). At discharge, 14% and 18.6% had an abnormal HADS score for depression and anxiety, respectively, which remained stable during follow-up and was not related to MoCA. Cognitive function, anxiety and depressive status remain stable in HF patients despite optimized HF therapy. Cognitive status shall be routinely screened to adopt attitudes that improve management as it has an impact on HF-related QoL and prognosis.

Heart and brain interactions in heart failure: Cognition, depression, anxiety, and related outcomes

BackgroundCognitive impairment, anxiety and depression are common in heart failure (HF) patients and its evolution is not fully understood. ObjectivesTo assess the cognitive status of HF patients over time, its relation to anxiety and depression, and its prognostic impact. MethodsProspective, longitudinal, single center study including patients enrolled in a structured program for follow-up after hospital admission for HF decompensation. Cognitive function, anxiety/depression state, HF-related quality of life (QoL) were assessed before discharge and during follow-up (between 6th and 12th month) using Montreal Cognitive Assessment (MoCA), Hospital Anxiety and Depression Scale (HADS) and Kansas City Cardiomyopathy Questionnaire, respectively. HF related outcomes were all cause readmissions, HF readmissions and the composite endpoint of all-cause readmissions or death. Results43 patients included (67±11.3 years, 69% male); followed-up for 8.2±2.1 months. 25.6% had an abnormal MoCA score that remained stable during follow-up (22.6±4.2 vs. 22.2±5.5; p=NS). MoCA score <22 at discharge conferred a sixfold greater risk of HF readmission [HR=6.42 (1.26-32.61); p=0.025], also predicting all-cause readmissions [HR=4.00 (1.15-13.95); p=0.03] and death or all-cause readmissions [HR=4.63 (1.37-15.67); p=0.014]. Patients with higher MoCA score showed a greater ability to deal with their disease (p=0.038). At discharge, 14% and 18.6% had an abnormal HADS score for depression and anxiety, respectively, which remained stable during follow-up and was not related to MoCA. ConclusionsCognitive function, anxiety and depressive status remain stable in HF patients despite optimized HF therapy. Cognitive status shall be routinely screened to adopt attitudes that improve management as it has an impact on HF-related QoL and prognosis.

The Effects of Spironolactone and Eplerenone on Left Ventricular Function Using Echocardiography in Symptomatic Patients With New-Onset Systolic Heart Failure: A Comparative Randomised Controlled Trial

Heart failure (HF), as a serious health condition, is characterised by the decreasing ability of the heart to pump enough blood around the body. This study compared the effects of spironolactone and eplerenone on the echocardiographic variables of the left ventricular (LV) function in symptomatic patients diagnosed with new-onset systolic HF. This study was a randomised controlled trial, including 85 symptomatic patients with new-onset systolic HF (namely, dilated cardiomyopathy). The patients were then randomly assigned to two groups in a 1:1 ratio and received either spironolactone or eplerenone in addition to optimal HF therapy for 6 months. Echocardiography was performed to visualise alterations in two-dimensional, pulse Doppler, tissue Doppler, and deformation indices of LV function. The results revealed that the group receiving eplerenone had a significantly greater increase in LV ejection fraction (LVEF) and a decrease in end-systolic LV internal diameter compared with the group receiving spironolactone (intergroup p=0.002 and p=0.006, respectively). There was a significant reduction in the end-diastolic LV internal diameter and the left atrial diameter, and a significant rise in tissue Doppler peak systolic mitral annular velocity in the group taking eplerenone; there were no significant changes in these variables in the group receiving spironolactone (intergroup p=0.006 and p=0.049, respectively). Accordingly, eplerenone had greater favourable effects on LVEF and the global longitudinal strain than spironolactone (B=5.207 [p<0.001] and B= -2.072 [p=0.044]), respectively. This study established that adding eplerenone to optimal HF therapy might be associated with more improvements in echocardiographic variables of LV function than spironolactone in symptomatic patients with new-onset systolic HF.

Hemodynamics and Clinical Implications of Occult Left Ventricular Dysfunction in Adults Undergoing Ebstein Anomaly Repair.

Left ventricular global longitudinal strain (LVGLS) can detect early phases of LV systolic dysfunction, but its application has not been studied in Ebstein anomaly. We hypothesized that LVGLS can detect early phases of LV systolic dysfunction and that patients with occult LV systolic dysfunction will have worse hemodynamics, end-organ dysfunction, and suboptimal postoperative LV reverse remodeling after tricuspid valve surgery in comparison to patients with normal LV systolic function. In this retrospective cohort study, 371 Ebstein patients that underwent tricuspid valve surgery were divided into 3 groups: normal LV systolic function (normal LVGLS and LV ejection fraction; n=244, 77%), occult LV systolic dysfunction (abnormal LVGLS with normal LV ejection fraction; n=44, 14%), and overt LV systolic dysfunction (abnormal LVGLS and LV ejection fraction; n=27, 9%). Compared with the normal LV function group, the occult group had smaller LV volume and cardiac output (2.1±0.4 versus 2.9±0.6 L/min per m2, P<0.001), worse end-organ dysfunction (glomerular filtration rate, 78±14 versus 91±18 mL/min per 1.73 m2, P=0.01), and suboptimal postoperative LV reverse remodeling. Although both the occult and overt groups had a similar degree of end-organ dysfunction (glomerular filtration rate, 78±14 versus 82±16 mL/min per 1.73 m2, P=0.3), the occult group was less likely to be on heart failure therapy (48% versus 96%, P<0.001). Abnormal LVGLS was associated with suboptimal postoperative LV reverse remodeling. These data suggest that LVGLS can potentially be used for risk stratification and provides a foundation for further studies to determine whether optimal heart failure therapy or tricuspid valve intervention can improve outcomes for LV systolic dysfunction in patients with Ebstein anomaly.

A randomized ablation-based atrial fibrillation rhythm control versus rate control trial in patients with heart failure and high burden atrial fibrillation: The RAFT-AF trial rationale and design

Heart failure (HF) and atrial fibrillation (AF) are 2 cardiac conditions that are increasing in prevalence and incidence. The 2 conditions frequently coexist, and are associated with increased morbidity and mortality. Catheter ablation of AF has been successfully performed in patients with HF, with an improvement in HF and AF, when compared to amiodarone, but further data is required to compare this to rate control. ObjectivesThe primary objective is to determine whether AF treated by catheter ablation, with or without antiarrhythmic drugs reduces all-cause mortality and hospitalizations for HF as compared with rate control in patients with HF and a high burden AF. MethodsThis is a multi-center prospective randomized open blinded endpoint (PROBE) study. Patients with NYHA class II-III HF (HF with reduced ejection fraction (<35%) or HF with preserved ejection fraction), and high burden AF are included in the trial. Patients are randomized to either rate control or catheter ablation-based AF rhythm control in a 1:1 ratio. Patients in the rate control group receive optimal HF therapy and rate control measures to achieve a resting hazard ratio (HR) < 80 bpm and 6-minute walk HR < 110 bpm. Patients randomized to catheter ablation-based AF rhythm control group receive optimal HF therapy and one or more aggressive catheter ablation, which include PV antral ablation and LA substrate ablation with or without adjunctive antiarrhythmic drug. The primary outcome is a composite of all-cause mortality and hospitalization for heart failure defined as an admission to a health care facility. The sample size is 600. Enrolment has been completed.

Estimated plasma volume status in heart failure: clinical implications and future directions.

Congestion is one of the main predictors of poor outcome in patients with heart failure (HF). Assessing and monitoring congestion is essential for optimizing HF therapy. Among the various available methods, serial measurements of estimated plasma volume (ePVS) using routine blood count and/or body weight (e.g., the Strauss, Duarte, Hakim formulas) may be useful in HF management. Further prospective study is warranted to determine whether ePVS can help optimize decongestion therapy (loop diuretics, mineralocorticoid receptor antagonists, SGLT2i) in various HF settings. This narrative review summarizes the recent evidence supporting the association of ePVS with clinical congestion and outcome(s) and discusses future directions for monitoring ePVS in HF.

Heart failure epidemiology and treatment in primary care: a retrospective cross-sectional study.

AimsHeart failure is one of the leading causes of morbidity and mortality worldwide, but little is known on heart failure epidemiology and treatment in primary care. This study described patients with heart failure treated by general practitioners, with focus on drug prescriptions and especially on the only specific treatment for heart failure with reduced ejection fraction, namely sacubitril/valsartan.Methods and resultsThis was a retrospective cross‐sectional study using data from an electronic medical record database of Swiss general practitioners from 2016 to 2019. Multilevel logistic regression was used to find determinants of sacubitril/valsartan prescription; odds ratios (ORs) and 95% confidence intervals (CIs) were reported. We identified 1288 heart failure patients (48.5% women; age: median 85 years, interquartile range 77–90 years) by means of diagnosis code, representing 0.5% of patients consulting a general practitioner during the observation period. About 73.6% received a renin–angiotensin–aldosterone system inhibitor, 67.8% a beta‐blocker, 34.6% a calcium channel blocker, 86.1% a diuretic, and 40.1% another cardiac drug. Sacubitril/valsartan was prescribed in 6% predominantly male patients (OR 2.10, CI 1.25–3.84), of younger age (OR 0.59 per increase in 10 years, CI 0.49–0.71), with diabetes mellitus (OR 1.76, CI 1.07–2.90). The recommended starting dose for sacubitril/valsartan was achieved in 67.1% and the target dose in 28.6% of patients.ConclusionsPrevalence of heart failure among patients treated by general practitioners was low. Considering the disease burden and association with multimorbidity, awareness of heart failure in primary care should be increased, with the aim to optimize heart failure therapy.