Twelve-month follow-up results from the SIRONA 2 clinical trial.

AIMS: In the SIRONA 2 trial, the safety and efficacy of pulmonary artery (PA) pressure (PAP)-guided heart failure (HF) management using a novel PAP sensor were assessed at 30 and 90 days, respectively, and both endpoints were met. The current study examines the prespecified secondary endpoints of safety and accuracy of the PA sensor along with HF hospitalizations and mortality, HF symptoms, functional capacity, quality of life, and patient compliance through 12 months. METHODS AND RESULTS: SIRONA 2 is a prospective, multi-centre, open-label, single-arm trial evaluating the Cordella™ PA Sensor System in 70 patients with New York Heart Association (NYHA) functional class III HF with a prior HF hospitalization and/or increase of N-terminal pro-brain natriuretic peptide within 12 months of enrolment. Sensor accuracy was assessed and compared with measurements obtained by standard right heart catheterization (RHC). Safety was defined as freedom from prespecified adverse events associated with use of the Cordella PA Sensor System and was assessed in all patients who entered the cath lab for PA sensor implant. HF hospitalizations and mortality, HF symptoms, functional capacity, quality of life, and patient compliance were also assessed. At 12 months, there was good agreement between the Cordella PA Sensor System and RHC, with the average difference for mean PAP being 2.9 ± 7.3 mmHg. The device safety profile was excellent with 98.4% freedom from device/system-related complications. There were no pressure sensor failures. HF hospitalizations and mortality were low with a rate of 0.33 event per patient year. Symptoms as assessed by NYHA (P < 0.0001) and functional capacity as measured by 6 min walk test (P = 0.02) were significantly improved. Patients' adherence to daily transmissions of PAP and vital signs measurements was 95%. CONCLUSIONS: Long-term follow-up of the SIRONA 2 trial supports the safety and accuracy of the Cordella PA Sensor System in enabling comprehensive HF management in NYHA class III HF patients.

Meta-Analysis and Metaregression of the Treatment Effect of Intravenous Iron in Iron-Deficient Heart Failure.

BACKGROUND: Guidelines recommend that intravenous iron should be considered to improve symptoms of heart failure (HF) and reduce the risk for HF admissions in patients after acute HF. OBJECTIVES: This study sought to analyze the effect of intravenous iron on cardiovascular (CV) death and HF admissions in a broad population of HF patients with iron deficiency and the relation with baseline transferrin saturation (TSAT). METHODS: A systematic review of all published randomized controlled trials assessing the effect of intravenous iron in patients with iron deficiency and HF between January 1, 2000, and August 26, 2023, was performed. The overall treatment effect was estimated using a fixed effect model for: 1) CV death; 2) CV death and HF admission; 3) first HF admission; and 4) total HF admissions. Metaregression through a mixed effect model was used to explore the impact of baseline TSAT in case of heterogeneity among trial results. RESULTS: A total of 14 randomized controlled trials were identified in the systematic review and retained in the meta-analysis. Aggregate-level data were included on 6,624 HF patients, 3,407 of whom were randomized to intravenous iron and 3,217 to placebo. Treatment with intravenous iron resulted in a lower risk for CV death (OR: 0.867 [95% CI: 0.755-0.955]; P = 0.0427), combined CV death and HF admission (OR: 0.838 [95% CI: 0.751-0.936]; P = 0.0015), first HF admission (OR: 0.855 [95% CI: 0.744-0.983]; P = 0.0281), and total HF admissions (rate ratio: 0.739 [95% CI: 0.661-0.827]; P < 0.0001). Significant heterogeneity among trial results was observed for first and total HF admissions. Metaregression suggested that some of the heterogeneity was related to the baseline TSAT of the enrolled population, with trials enrolling patients with lower TSAT exhibiting a large effect size on HF-related events. CONCLUSIONS: The totality of data suggests that treatment with intravenous iron reduces both CV death and HF-related events in a broad population with HF. A lower baseline TSAT might be important for the effect on HF-related events.

Patient phenotype profiling in heart failure with preserved ejection fraction to guide therapeutic decision making. A scientific statement of the Heart Failure Association, the European Heart Rhythm Association of the European Society of Cardiology, and the European Society of Hypertension.

Heart failure with preserved ejection fraction (HFpEF) represents a highly heterogeneous clinical syndrome affected in its development and progression by many comorbidities. The left ventricular diastolic dysfunction may be a manifestation of various combinations of cardiovascular, metabolic, pulmonary, renal, and geriatric conditions. Thus, in addition to treatment with sodium-glucose cotransporter 2 inhibitors in all patients, the most effective method of improving clinical outcomes may be therapy tailored to each patient's clinical profile. To better outline a phenotype-based approach for the treatment of HFpEF, in this joint position paper, the Heart Failure Association of the European Society of Cardiology, the European Heart Rhythm Association and the European Hypertension Society, have developed an algorithm to identify the most common HFpEF phenotypes and identify the evidence-based treatment strategy for each, while taking into account the complexities of multiple comorbidities and polypharmacy.

Rationale and Design of the Proactive-HF Trial for Managing Patients With NYHA Class III Heart Failure by Using the Combined Cordella Pulmonary Artery Sensor and the Cordella Heart Failure System.

BACKGROUND: Optimizing guideline-directed medical therapy (GDMT) and monitoring congestion in patients with heart failure (HF) are key to disease management and preventing hospitalizations. A pulmonary artery pressure (PAP)-guided HF management system providing access to body weight, blood pressure, heart rate, blood oxygen saturation, PAP, and symptoms, may provide new insights into the effects of patient engagement and comprehensive care for remote GDMT titration and congestion management. METHODS: The PROACTIVE-HF study was originally approved in 2018 as a prospective, randomized, controlled, single-blind, multicenter trial to evaluate the safety and effectiveness of the Cordella PAP Sensor in patients with HF and with New York Heart Association (NYHA) functional class III symptoms. Since then, robust clinical evidence supporting PAP-guided HF management has emerged, making clinical equipoise and enrolling patients into a standard-of-care control arm challenging. Therefore, PROACTIVE-HF was changed to a single-arm trial in 2021 with prespecified safety and effectiveness endpoints to provide evidence for a similar risk/benefit profile as the CardioMEMS HF System. CONCLUSION: The single-arm PROACTIVE-HF trial is expected to further demonstrate the benefits of PAP-guided HF management of patients with NYHA class III HF. The addition of vital signs, patient engagement and self-reported symptoms may provide new insights into remote GDMT titration and congestion management.

Assessing intrinsic renal sodium avidity in acute heart failure: implications in predicting and guiding decongestion.

AIM: Intrinsic renal sodium avidity (IRSA) is a hallmark feature of acute heart failure (AHF) and can be measured by evaluating the urinary sodium (UNa) concentration. The aim of this study is to assess the role of measuring IRSA through a random Una-sample and its association with decongestive response. METHODS AND RESULTS: A post-hoc analysis of the ROSE-AHF trial was performed in all patients with a random UNa spot sample before randomization (n = 339/360). Patients were categorized according to tertiles of UNa as high (range 19-40 mmol/L), intermediate (range 41-68 mmol/L), or low (range 69-139 mmol/L) IRSA. Linear mixed effect models and ANCOVA were used to assess the relation with decongestive effectiveness measured by: (i) weight change, (ii) visual analogue scale (VAS) improvement, (iii) N-terminal pro-B-type natriuretic peptide (NT-proBNP) change, (iv) natriuretic response (UNa in mmol/L), (v) 72 h natriuresis (mmol), (vi) oedema resolution, and (vii) length of stay. High IRSA patients had less improvement in decongestive metrics, including weight loss (p = 0.028), VAS improvement, NT-proBNP decrease, natriuretic response (p-time interaction <0.001 for all), had lower total natriuresis (high IRSA 438 ± 141 mmol, intermediate IRSA 526 ± 320 mmol, and low IRSA 603 ± 276 mmol; p < 0.001), exhibited more oedema at 72 h (p = 0.005), and had a longer length of stay (p = 0.015). Incremental loop diuretic dose titration (± 4 times home dose) after >24 h, resulted in an increase in natriuretic response in the high IRSA group, however cumulative natriuresis still remained lower at 72 h (p < 0.001). Longitudinal UNa profiling of patients with low IRSA showed physiologic breaking in the UNa pattern, associated with attaining decongestion and slight increase in creatinine and cystatin C, forming a potential signal of complete decongestion. CONCLUSIONS: A simple random UNa sample at the time of AHF, gives insight into IRSA which is consistently associated with decongestive effectiveness across multiple metrics, offering an opportunity for early AHF care improvement.

Impact of Sacubitril/Valsartan Compared With Ramipril on Cardiac Structure and Function After Acute Myocardial Infarction: The PARADISE-MI Echocardiographic Substudy.

BACKGROUND: Angiotensin-converting enzyme inhibitors attenuate left ventricular (LV) enlargement after acute myocardial infarction (AMI). Preclinical data suggest similar benefits with combined angiotensin receptor neprilysin inhibition, but human data are conflicting. The PARADISE-MI Echo Study (Prospective ARNI Versus ACE Inhibitor Trial to Determine Superiority in Reducing Heart Failure Events After Myocardial Infarction) tested the effect of sacubitril/valsartan compared with ramipril on LV function and adverse remodeling after high risk-AMI. METHODS: In a prespecified substudy, 544 PARADISE-MI participants were enrolled in the Echo Study to undergo protocol echocardiography at randomization and after 8 months. Patients were randomized within 0.5 to 7 days of presentation with their index AMI to receive a target dose of sacubitril/valsartan 200 mg or ramipril 5 mg twice daily. Echocardiographic measures were performed at a core laboratory by investigators blinded to treatment assignment. The effect of treatment on change in echo measures was assessed with ANCOVA with adjustment for baseline value and enrollment region. The primary end points were change in LV ejection fraction (LVEF) and left atrial volume (LAV), and prespecified secondary end points included changes in LV end-diastolic and end-systolic volumes. RESULTS: Mean age was 64±12 years; 26% were women; mean LVEF was 42±12%; and LAV was 49±17 mL. Of 544 enrolled patients, 457 (84%) had a follow-up echo at 8 months (228 taking sacubitril/valsartan, 229 taking ramipril). There was no significant difference in change in LVEF (P=0.79) or LAV (P =0.62) by treatment group. Patients randomized to sacubitril/valsartan demonstrated less increase in LV end-diastolic volume (P=0.025) and greater decline in LV mass index (P=0.037), increase in tissue Doppler e'lat (P=0.005), decrease in E/e'lat (P=0.045), and decrease in tricuspid regurgitation peak velocity (P=0.024) than patients randomized to ramipril. These differences remained significant after adjustment for differences in baseline characteristics. Baseline LVEF, LV end-diastolic volume, LV end-systolic volume, LV mass index, LAV, and Doppler-based diastolic indices were associated with risk of cardiovascular death or incident heart failure. CONCLUSIONS: Treatment with sacubitril/valsartan compared with ramipril after AMI did not result in changes in LVEF or LAV at 8 months. Patients randomized to sacubitril/valsartan had less LV enlargement and greater improvement in filling pressure. Measures of LV size, systolic function, and diastolic properties were predictive of cardiovascular death and incident heart failure after AMI in this contemporary, well-treated cohort. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02924727.

Electrical Dyssynchrony in Cardiac Amyloidosis: Prevalence, Predictors, Clinical Correlates, and Outcomes.

BACKGROUND: Conduction-system involvement in cardiac amyloidosis (CA) is common. The prevalence, clinical correlates and impact on outcome related to ventricular electrical dyssynchrony in CA remain insufficiently elucidated. METHODS: Data from a prospectively maintained registry of patients with CA diagnosed in the Cleveland Clinic's amyloidosis clinic was used to determine the frequency of electrical dyssynchrony (defined as a QRS > 130 msec). The relation with the clinical profile and clinical outcome was assessed. To determine the impact of hypertrophy on QRS prolongation, a QRS-matched cohort without CA was used for comparison of cardiac magnetic resonance imaging. RESULTS: A total of 1140 patients with CA (39% AL, 61% TTR) were evaluated, of whom 230 (20%) had electrical dyssynchrony. The type of conduction block was predominantly a right bundle branch block (BBB, 48%) followed by left BBB (35%) and intraventricular conduction delay (17%). Presence of transthyretin amyloidosis (ATTR-CA), older age, male gender, white race, and coronary artery disease were independently (P< 0.05 for all) associated with electrical dyssynchrony, and patients were more commonly prescribed a mineralocorticoid receptor antagonist. In ATTR-CA, specifically, every increase in ATTR-CA disease stage was associated with a 1.55-fold (1.23--1.95; P< 0.001) increased odds for electrical dyssynchrony. In a subset of patients with CA who underwent cardiac magnetic resonance imaging (n = 41), left ventricular mass index was unrelated to the QRS duration (r = 0.187; P = 0.283) in CA, in contrast to a non-CA QRS-matched cohort (r = 0.397; P< 0.001). Patients with electrical dyssynchrony were more symptomatic at initial presentation, as illustrated by a higher New York Heart Association class (P= 0.041). During a median follow-up of 462 days (IQR:138--996 days), a higher proportion of patients with electrical dyssynchrony died from all-cause death (P= 0.037) or developed a permanent pacing indication (3% vs 10.4%; P< 0.001) during follow-up. CONCLUSION: Electrical dyssynchrony is common in CA, especially in ATTR-CA, and is associated with worse functional status and clinical outcome. Given the high rate of permanent pacing indications at follow-up, additional studies are necessary to determine the best monitoring and pacing strategies in CA.

Prevention of sudden death in heart failure with reduced ejection fraction: do we still need an implantable cardioverter-defibrillator for primary prevention?

Sudden death is a devastating complication of heart failure (HF). Current guidelines recommend an implantable cardioverter-defibrillator (ICD) for prevention of sudden death in patients with HF and reduced ejection fraction (HFrEF) specifically those with a left ventricular ejection fraction ≤35% after at least 3 months of optimized HF treatment. The benefit of ICD in patients with symptomatic HFrEF caused by coronary artery disease has been well documented; however, the evidence for a benefit of prophylactic ICD implantation in patients with HFrEF of non-ischaemic aetiology is less strong. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, beta-blockers (BB), and mineralocorticoid receptor antagonists (MRA) block the deleterious actions of angiotensin II, norepinephrine, and aldosterone, respectively. Neprilysin inhibition potentiates the actions of endogenous natriuretic peptides that mitigate adverse ventricular remodelling. BB, MRA, angiotensin receptor-neprilysin inhibitor (ARNI) have a favourable effect on reduction of sudden cardiac death in HFrEF. Recent data suggest a beneficial effect of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in reducing serious ventricular arrhythmias and sudden cardiac death in patients with HFrEF. So, in the current era of new drugs for HFrEF and with the optimal use of disease-modifying therapies (BB, MRA, ARNI and SGLT2i), we might need to reconsider the need and timing for use of ICD as primary prevention of sudden death, especially in HF of non-ischaemic aetiology.

The effect of intravenous ferric carboxymaltose on right ventricular function - insights from the IRON-CRT trial.

AIMS: Ferric carboxymaltose (FCM) improves left ventricular function in heart failure with reduced ejection fraction (HFrEF). Yet, the effect of FCM on right ventricular (RV) function remains insufficiently elucidated. METHODS AND RESULTS: This is a pre-defined analysis of the IRON-CRT trial in which symptomatic HFrEF patients with iron deficiency and reduced left ventricular ejection fraction (LVEF) despite optimal medical therapy and cardiac resynchronization therapy (CRT) underwent 1:1 randomization to FCM or placebo in a double-blind fashion. RV function was measured as the change from baseline to 3-month follow-up in RV fractional area change (FAC), tricuspid annular plane systolic excursion (TAPSE) and pulsed Doppler peak velocity at the RV lateral annulus (RV S'), systolic pulmonary artery pressure (SPAP) and its coupling to the right ventricle (TAPSE/SPAP ratio). The RV contractile reserve was measured as the change in TAPSE during incremental pacing at 70, 90 and 110 bpm. A total of 75 patients underwent randomization and received FCM (n = 37) or placebo (n = 38). At baseline 72.5% had RV dysfunction and 70% had RV dilatation. At 3-month follow-up, patients receiving FCM had a significant improvement in RV FAC (+4.1% [+1.4% - +6.9%] vs. -2.2% [-4.9% - +0.6%] in the placebo group, p = 0.002) and TAPSE (+0.98 mm [+0.28 mm - +1.62 mm] vs. -0.19 mm [-0.85 mm - +0.48 mm] in the placebo group, p = 0.020), but not RV S'. Patients receiving FCM had a numerically lower SPAP (p = 0.073) and significant improvement in TAPSE/SPAP ratio (+0.097 [+0.048 - +0.146] vs. +0.002 [-0.046 - +0.051] in the placebo group, p = 0.008). At baseline both groups had diminished RV contractile reserve during incremental pacing, which was attenuated at 3-month follow-up in the FCM group (p = 0.004). Patients manifesting more RV function improvement were more likely to exhibit higher degrees of LVEF improvement (p < 0.05 for all). CONCLUSIONS: Treatment with FCM in HFrEF patients results in an improvement in RV function and structure and improves the RV contractile reserve.

The effect of intravenous ferric carboxymaltose on cardiac reverse remodelling following cardiac resynchronization therapy-the IRON-CRT trial.

AIMS: Iron deficiency is common in heart failure with reduced ejection fraction (HFrEF) and negatively affects cardiac function and structure. The study the effect of ferric carboxymaltose (FCM) on cardiac reverse remodelling and contractile status in HFrEF. METHODS AND RESULTS: Symptomatic HFrEF patients with iron deficiency and a persistently reduced left ventricular ejection fraction (LVEF <45%) at least 6 months after cardiac resynchronization therapy (CRT) implant were prospectively randomized to FCM or standard of care (SOC) in a double-blind manner. The primary endpoint was the change in LVEF from baseline to 3-month follow-up assessed by three-dimensional echocardiography. Secondary endpoints included the change in left ventricular end-systolic (LVESV) and end-diastolic volume (LVEDV) from baseline to 3-month follow-up. Cardiac performance was evaluated by the force-frequency relationship as assessed by the slope change of the cardiac contractility index (CCI = systolic blood pressure/LVESV index) at 70, 90, and 110 beats of biventricular pacing. A total of 75 patients were randomized to FCM (n = 37) or SOC (n = 38). At baseline, both treatment groups were well matched including baseline LVEF (34 ± 7 vs. 33 ± 8, P = 0.411). After 3 months, the change in LVEF was significantly higher in the FMC group [+4.22%, 95% confidence interval (CI) +3.05%; +5.38%] than in the SOC group (-0.23%, 95% CI -1.44%; +0.97%; P < 0.001). Similarly, LVESV (-9.72 mL, 95% CI -13.5 mL; -5.93 mL vs. -1.83 mL, 95% CI -5.7 mL; 2.1 mL; P = 0.001), but not LVEDV (P = 0.748), improved in the FCM vs. the SOC group. At baseline, both treatment groups demonstrated a negative force-frequency relationship, as defined by a decrease in CCI at higher heart rates (negative slope). FCM resulted in an improvement in the CCI slope during incremental biventricular pacing, with a positive force-frequency relationship at 3 months. Functional status and exercise capacity, as measured by the Kansas City Cardiomyopathy Questionnaire and peak oxygen consumption, were improved by FCM. CONCLUSIONS: Treatment with FCM in HFrEF patients with iron deficiency and persistently reduced LVEF after CRT results in an improvement of cardiac function measured by LVEF, LVESV, and cardiac force-frequency relationship.

Self-care of heart failure patients: practical management recommendations from the Heart Failure Association of the European Society of Cardiology.

Self-care is essential in the long-term management of chronic heart failure. Heart failure guidelines stress the importance of patient education on treatment adherence, lifestyle changes, symptom monitoring and adequate response to possible deterioration. Self-care is related to medical and person-centred outcomes in patients with heart failure such as better quality of life as well as lower mortality and readmission rates. Although guidelines give general direction for self-care advice, health care professionals working with patients with heart failure need more specific recommendations. The aim of the management recommendations in this paper is to provide practical advice for health professionals delivering care to patients with heart failure. Recommendations for nutrition, physical activity, medication adherence, psychological status, sleep, leisure and travel, smoking, immunization and preventing infections, symptom monitoring, and symptom management are consistent with information from guidelines, expert consensus documents, recent evidence and expert opinion.

Role of cardiovascular imaging in cancer patients receiving cardiotoxic therapies: a position statement on behalf of the Heart Failure Association (HFA), the European Association of Cardiovascular Imaging (EACVI) and the Cardio-Oncology Council of the European Society of Cardiology (ESC).

Cardiovascular (CV) imaging is an important tool in baseline risk assessment and detection of CV disease in oncology patients receiving cardiotoxic cancer therapies. This position statement examines the role of echocardiography, cardiac magnetic resonance, nuclear cardiac imaging and computed tomography in the management of cancer patients. The Imaging and Cardio-Oncology Study Groups of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) in collaboration with the European Association of Cardiovascular Imaging (EACVI) and the Cardio-Oncology Council of the ESC have evaluated the current evidence for the value of modern CV imaging in the cardio-oncology field. The most relevant echocardiographic parameters, including global longitudinal strain and three-dimensional ejection fraction, are proposed. The protocol for baseline pre-treatment evaluation and specific surveillance algorithms or pathways for anthracycline chemotherapy, HER2-targeted therapies such as trastuzumab, vascular endothelial growth factor tyrosine kinase inhibitors, BCr-Abl tyrosine kinase inhibitors, proteasome inhibitors and immune checkpoint inhibitors are presented. The indications for CV imaging after completion of oncology treatment are considered. The typical consequences of radiation therapy and the possibility of their identification in the long term are also summarized. Special populations are discussed including female survivors planning pregnancy, patients with carcinoid disease, patients with cardiac tumours and patients with right heart failure. Future directions and ongoing CV imaging research in cardio-oncology are discussed.

Impact of Sacubitril-Valsartan on Markers of Glomerular Function.

PURPOSE OF REVIEW: To provide pathophysiological and clinical insights into the effects of sacubitril/valsartan on glomerular function. RECENT FINDINGS: Heart failure and glomerular dysfunction are closely intertwined. In addition to reduced heart failure hospitalization and all-cause mortality, patients treated with sacubitril/valsartan have a slower deterioration of glomerular filtration rate over time compared with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. The effects of sacubitril/valsartan are probably mediated through enhancement of natriuretic peptides, reduction of glomerular inflammation and fibrosis, and relaxation of mesangial cells and podocytes. Further studies will elucidate underlying pathophysiological mechanisms of sacubitril/valsartan on glomerular function and their prognostic significance in subjects with and without heart failure.

Improved cardiac and venous pressures during hospital stay in patients with acute heart failure: an echocardiography and biomarkers study.

AIMS: Changes in echocardiographic parameters and biomarkers of cardiac and venous pressures or estimated plasma volume during hospitalization associated with decongestive treatments in acute heart failure (AHF) patients with either preserved left ventricular ejection fraction (LVEF) (HFPEF) or reduced LVEF (HFREF) are poorly assessed. METHODS AND RESULTS: From the metabolic road to diastolic heart failure: diastolic heart failure (MEDIA-DHF) study, 111 patients were included in this substudy: 77 AHF (43 HFPEF and 34 HFREF) and 34 non-cardiac dyspnea patients. Echocardiographic measurements and blood samples were obtained within 4 h of presentation at the emergency department and before hospital discharge. In AHF patients, echocardiographic indices of cardiac and venous pressures, including inferior vena cava diameter [from 22 (16-24) mm to 13 (11-18) mm, P = 0.009], its respiratory variability [from 32 (8-44) % to 43 (29-70) %, P = 0.04], medial E/e' [from 21.1 (15.8-29.6) to 16.6 (11.7-24.3), P = 0.004], and E wave deceleration time [from 129 (105-156) ms to 166 (128-203) ms, P = 0.003], improved during hospitalization, similarly in HFPEF and HFREF patients. By contrast, no changes were seen in non-cardiac dyspnea patients. In AHF patients, all plasma biomarkers of cardiac and venous pressures, namely B-type natriuretic peptide [from 935 (514-2037) pg/mL to 308 (183-609) pg/mL, P < 0.001], mid-regional pro-atrial natriuretic peptide [from 449 (274-653) pmol/L to 366 (242-549) pmol/L, P < 0.001], and soluble CD-146 levels [from 528 (406-654) ng/mL to 450 (374-529) ng/mL, P = 0.003], significantly decreased during hospitalization, similarly in HFPEF and HFREF patients. Echocardiographic parameters of cardiac chamber dimensions [left ventricular end-diastolic volume: from 120 (76-140) mL to 118 (95-176) mL, P = 0.23] and cardiac index [from 2.1 (1.6-2.6) mL/min/m2 to 1.9 (1.4-2.4) mL/min/m2 , P = 0.55] were unchanged in AHF patients, except tricuspid annular plane systolic excursion (TAPSE) that improved during hospitalization [from 16 (15-19) mm to 19 (17-21) mm, P = 0.04]. Estimated plasma volume increased in both AHF [from 4.8 (4.2-5.6) to 5.1 (4.4-5.8), P = 0.03] and non-cardiac dyspnea patients (P = 0.01). Serum creatinine [from 1.18 (0.90-1.53) to 1.19 (0.86-1.70) mg/dL, P = 0.89] and creatinine-based estimated glomerular filtration rate [from 59 (40-75) mL/min/1.73m2 to 56 (38-73) mL/min/1.73m2 , P = 0.09] were similar, while plasma cystatin C [from 1.50 (1.20-2.27) mg/L to 1.78 (1.33-2.59) mg/L, P < 0.001] and neutrophil gelatinase associated lipocalin (NGAL) [from 127 (95-260) ng/mL to 167 (104-263) ng/mL, P = 0.004] increased during hospitalization in AHF. CONCLUSIONS: Echocardiographic parameters and plasma biomarkers of cardiac and venous pressures improved during AHF hospitalization in both acute HFPEF and HFREF patients, while cardiac chamber dimensions, cardiac output, and estimated plasma volume showed minimal changes.

Indications and diagnostic yield of endomyocardial biopsies for unexplained cardiomyopathy, a single center experience.

Background: Endomyocardial biopsies (EMBs) remain the golden standard to diagnose underlying pathophysiologic process in heart failure (HF), when potential therapeutic decisions cannot be made by non-invasive techniques. However, changes in the field of non-invasive diagnostic testing might have an impact on the need for performing an EMB in certain scenarios.Methods: We performed a retrospective analysis of consecutive EMBs performed in a single, non-academic, tertiary-care centre. EMBs were performed between February 2009 and March 2018. Baseline characteristics including non-invasive imaging and hemodynamic profile were assessed. Indications of EMBs were analysed in accordance with the 2007-AHA/ACC/ESC-scientific statement on EMBs.Results: A total of 57 patients (74% male) were included. The overall diagnostic yield was 58%, with a trend towards a higher yield in left-side (64%) versus right-side EMBs (45%; p = .346). The majority of patients (88%) underwent EMBs for a class IIa-recommendation, 9% for a class-I recommendation and the remaining patients for a class IIb-indication. Of the EMBs for a class IIa indication, 82% (n = 47) was for an unexplained restrictive cardiomyopathy, in which 53% (n = 25) revealed a diagnosis (of whom n = 23 patients had amyloidosis). Subtyping of the EMBs with a pathologic diagnosis of amyloidosis revealed that 52% (n = 12) had transthyretin amyloidosis (ATTR) and 43% (n = 10) had light-chain amyloidosis (AL). Overall one major (1.7%) and one minor (1.7%) complication occurred following the EMB-procedure.Conclusions: When following the AHA/ACC/ESC-scientific statement on EMBs, the performance of EMBs had a high diagnostic yield, with acceptable complication rates. However, in patients presenting with an unexplained restricted cardiomyopathy, technetium-labelled bone scanning could offer a non-invasive approach to establishing the diagnosis of ATTR, mitigating the need for EMBs in a subset of patients.

The importance of dose optimisation in the treatment of iron deficiency in heart failure.

Background: Treatment with ferric carboxymaltose (FCM) is limited to 1 g during one administration, which is insufficient in patients with a higher body weight or low haemoglobin (Hb). As a consequence, under-dosing might be common in clinical practice, yet the consequences remain unstudied.Methods: We retrospectively assessed all HFrEF-patients with iron-deficiency (ferritin <100 µg/l or between 100 and 300 µg/l if TSAT < 20%) receiving treatment with FCM between 2015 and 2017. This time-frame was chosen as during this we used a 1-g FCM-regimen for all patients (unless Hb = 14-15 mg/dl, than 500 mg). We compared the actual given dose versus the calculated target dose (according to the SmPC, with the difference between both being the dose deficit). We assessed the impact of dose deficits on clinical and biochemical status after 12 weeks.Results: A total of 211 HFrEF patients were analysed. The actual given dose FCM was 918 ± 188 mg, while the calculated target dose was 1308 ± 470 mg. In 121(61%) patients, a standard dose of 1-g FCM resulted in a dose deficit, of whom 93 had a dose deficit of 500 mg and 35 had a dose deficit of 1000 mg. Follow-up was available in 81% of patients (median = 12 weeks). A dose deficit of 500 mg was associated with a 4.93 higher odds, while a dose deficit of 1000 mg was associated with a 7.78 higher odds of residual iron deficiency. After adjusting for baseline NYHA-class, a dose deficit was associated with less symptomatic improvement. During 442 ± 292 days of follow-up, 68 patients were readmitted with heart failure and 15 patients died. In an univariate model (but not in a multivariate model), a dose deficit was associated with adverse clinical outcome.Conclusion: A majority of HFrEF patients with iron deficiency require doses exceeding 1 g of FCM, and thus require follow-up appointments to correct a residual dose deficit. A residual dose deficit is associated with less functional and biochemical improvement.

Endurance Exercise Intervention Is Beneficial to Kidney Function in a Rat Model of Isolated Abdominal Venous Congestion: a Pilot Study.

In this study, the effects of moderate intense endurance exercise on heart and kidney function and morphology were studied in a thoracic inferior vena cava constricted (IVCc) rat model of abdominal venous congestion. After IVC surgical constriction, eight sedentary male Sprague-Dawley IVCc rats (IVCc-SED) were compared to eight IVCc rats subjected to moderate intense endurance exercise (IVCc-MOD). Heart and kidney function was examined and renal functional reserve (RFR) was investigated by administering a high protein diet (HPD). After 12 weeks of exercise training, abdominal venous pressure, indices of body fat content, plasma cystatin C levels, and post-HPD urinary KIM-1 levels were all significantly lower in IVCc-MOD versus IVCc-SED rats (P < 0.05). RFR did not differ between both groups. The implementation of moderate intense endurance exercise in the IVCc model reduces abdominal venous pressure and is beneficial to kidney function.

Rationale and design of the IRON-CRT trial: effect of intravenous ferric carboxymaltose on reverse remodelling following cardiac resynchronization therapy.

AIMS: Iron deficiency is common in heart failure with reduced ejection fraction (HFrEF). In patients with cardiac resynchronization therapy (CRT), it is associated with a diminished reverse remodelling response and poor functional improvement. The latter is partially related to a loss in contractile force at higher heart rates (negative force-frequency relationship). METHODS AND RESULTS: The effect of intravenous ferric carboxymaltose on reverse remodelling following cardiac resynchronization therapy (IRON-CRT) trial is a multicentre, prospective, randomized, double-blind controlled trial in HFrEF patients who experienced incomplete reverse remodelling (defined as a left ventricular ejection fraction below <45%) at least 6 months after CRT. Additionally, patients need to have iron deficiency defined as a ferritin below 100 µg/L irrespective of transferrin saturation or a ferritin between 100 and 300 µg/L with a transferrin saturation <20%. Patients will be randomized to either intravenous ferric carboxymaltose (dose based according to Summary of Product Characteristics) or intravenous placebo. The primary objective is to evaluate the effect of ferric carboxymaltose on metrics of cardiac reverse remodelling and contractility, measured by the primary endpoint, change in left ventricular ejection fraction assessed by three-dimensional (3D) echo from baseline to 3 month follow-up and the secondary endpoints change in left ventricular end-systolic and end-diastolic volume. The secondary objective is to determine if ferric carboxymaltose is capable of improving cardiac contractility in vivo, by assessing the force-frequency relationship through incremental biventricular pacing. A total of 100 patients will be randomized in a 1:1 fashion. CONCLUSIONS: The IRON-CRT trial will determine the effect of ferric carboxymaltose on cardiac reverse remodelling and rate-dependent cardiac contractility in HFrEF patients.