The impact of spinal anesthesia on cardiac function in euvolemic vascular surgery patients: insights from echocardiography and biomarkers.

Existing evidence of the effect of spinal anesthesia (SA) on cardiac systolic function is scarce and inconclusive. This study aimed to evaluate the effects induced by a single injection of SA for elective vascular surgery on left (LV) and right (RV) ventricular systolic performance using transthoracic echocardiography (TTE). A prospective study. Single-center study, university hospital. Adult patients undergoing elective vascular surgery with SA. During patients' evaluations fluid administration was targeted using arterial waveform monitoring. All patients underwent TTE studies before and after SA induction for the assessment of indices reflective of LV and RV systolic function. Blood samples were drawn to measure troponin and brain natriuretic peptide (BNP) levels. A total of 62 patients (88.7% males, 71.00 ± 9.42 years) were included in the study. The primary outcome was the difference before and after SA in LV ejection fraction (LVEF) and tricuspid annular plane systolic excursion (TAPSE). In total population, LVEF significantly increased after SA 53.07% [16.51]vs 53.86% [13.28]; p < 0.001). End-systolic volume (ESV, 69.50 [51.50] vs. 65.00 [29.50] ml; p < 0.001) decreased while stroke volume (SV) insignificantly increased (70.51 ± 16.70 vs. 73.00 ± 18.76 ml; p = 0.131) during SA. TAPSE remained unchanged (2.23 [0.56] vs. 2.25 [0.69] mm; p = 0.558). In patients with impaired compared to those with preserved LV systolic function, the changes evidenced in LVEF (7.49 ± 4.15 vs. 0.59 ± 2.79; p < 0.001), ESV (-18.13 ± 18.20 vs-1.53 ± 9.09; p < 0.001) and SV (8.71 ± 11.96 vs-1.43 ± 11.89; p = 0.002) were greater. This study provides evidence that SA in patients undergoing elective vascular surgery improved LV systolic function, while changes in RV systolic function are minimal.

Heart failure risk assessment in patients with hypertrophic cardiomyopathy based on the H2FPEF score.

AIMS: The aim of this study was to investigate whether the H2FPEF score, which was developed to improve the diagnosis of heart failure (HF) with preserved ejection fraction, is associated with HF outcomes in patients with hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: Patients with HCM and preserved left ventricular ejection fraction (LVEF ≥50%) were included from a multicentre registry and the H2FPEF score was calculated. Patients were divided into three groups: low (0-1), intermediate (2-5) and high (6-9) H2FPEF score. The primary combined endpoint was a composite of all-cause death and HF admissions, while the secondary endpoints were all-cause death and HF admissions separately. A total of 955 patients were included (age 51 ± 17 years, 310 [32.5%] female). Patients with a high H2FPEF score (n = 105) were more often female, and presented with more symptoms and comorbidities. On echocardiography, patients with a high H2FPEF score had lower LVEF, more impaired diastolic function and more frequently left ventricular outflow tract obstruction. During follow-up (median 90 months [interquartile range 49-176]), 103 (11%) patients died and 57 (6%) patients had a first HF hospitalization. Event-free survival rate for the primary combined and secondary endpoints was lower for patients with an intermediate and high H2FPEF score. On multivariate Cox regression analysis, female sex (hazard ratio [HR] 1.670, 95% confidence interval [CI] 1.157-2.410; p = 0.006), Asian ethnicity (HR 6.711, 95% CI 4.076-11.048; p < 0.001), ischaemic heart disease (HR 1.732, 95% CI 1.133-2.650; p = 0.011), left atrial diameter (HR 1.028, 95% CI 1.005-1.051; p = 0.016) and intermediate (HR 2.757, 95% CI 1.612-4.713; p < 0.001) or high H2FPEF score (HR 3.689, 95% CI 1.908-7.134; p < 0.001) were independently associated with the primary combined endpoint. CONCLUSION: The H2FPEF score is independently associated with HF outcome in patients with HCM and may be considered for risk stratification.

Cardiac magnetic resonance for ventricular arrhythmias: a systematic review and meta-analysis.

BACKGROUND: Cardiac magnetic resonance (CMR) allows comprehensive myocardial tissue characterisation, revealing areas of myocardial inflammation or fibrosis that may predispose to ventricular arrhythmias (VAs). With this study, we aimed to estimate the prevalence of structural heart disease (SHD) and decipher the prognostic implications of CMR in selected patients presenting with significant VAs. METHODS: Electronic databases were searched for studies enrolling adult patients that underwent CMR for diagnostic or prognostic purposes in the setting of significant VAs. A random effects model meta-analysis of proportions was performed to estimate the prevalence of SHD. HRs were pooled together in order to evaluate the prognostic value of CMR. RESULTS: The prevalence of SHD was reported in 18 studies. In all-comers with significant VAs, the pooled rate of SHD post-CMR evaluation was 39% (24% in the subgroup of premature ventricular contractions and/or non-sustained ventricular tachycardia vs 63% in the subgroup of more complex VAs). A change in diagnosis after use of CMR ranged from 21% to 66% with a pooled average of 35% (29%-41%). A non-ischaemic cardiomyopathy was the most frequently identified SHD (56%), followed by ischaemic heart disease (21%) and hypertrophic cardiomyopathy (5%). After pooling together data from six studies, we found that the presence of late gadolinium enhancement was associated with increased risk of major adverse outcomes in patients with significant VAs (pooled HR: 1.79; 95% CI 1.33 to 2.42). CONCLUSION: CMR is a valuable tool in the diagnostic and prognostic evaluation of patients with VAs. CMR should be considered early after initial evaluation in the diagnostic algorithm for VAs of unclear aetiology as this strategy may also define prognosis and improve risk stratification.

Prognostic implications of genotype findings in non-ischaemic dilated cardiomyopathy: A network meta-analysis.

AIMS: Evidence on the relative impact of diverse genetic backgrounds associated with non-ischaemic dilated cardiomyopathy (DCM) remains contradictory. This study sought to synthesize the available data regarding long-term outcomes of different gene groups in DCM. METHODS AND RESULTS: Electronic databases were systematically screened to identify studies reporting prognostic data on pre-specified gene groups. Those included pathogenic/likely pathogenic (P/LP) variants, truncating titin variants (TTNtv), lamin A/C variants (LMNA), and desmosomal proteins. Outcomes were divided into composite adverse events (CAEs), malignant ventricular arrhythmic events (MVAEs) and heart failure events (HFEs). A total of 26 studies (n = 7255) were included in the meta-analysis and 6791 patients with genotyped DCM were analysed. Patients with P/LP variants had a higher risk for CAEs (odds ratio [OR] 2.10, 95% confidence interval [CI] 1.67-2.65), MVAEs (OR 1.86, 95% CI 1.52-2.26), and HFEs (OR 2.01, 95% CI 1.08-3.73) than genotype-negative patients. The presence of TTNtv was linked to a higher risk for CAEs (OR 1.78, 95% CI 1.20-2.63), but not MVAEs or HFEs. LMNA and desmosomal groups suffered a higher risk for CAEs, MVAEs, and HFEs compared to non-LMNA and non-desmosomal groups, respectively. When genes were indirectly compared, the presence of LMNA resulted in a more detrimental effect that TTNtv, with respect to all composite outcomes but no significant difference was found between LMNA and desmosomal genes. Desmosomal genes harboured a higher risk for MVAEs compared to TTNtv. CONCLUSIONS: Different genetic substrates associated with DCM result in divergent natural histories. Routine utilization of genetic testing should be employed to refine risk stratification and inform therapeutic strategies in DCM.

Multiorgan Congestion Assessment by Venous Excess Ultrasound Score in Acute Heart Failure.

BACKGROUND: This study sought to explore the prevalence and clinical utility of different patterns of multiorgan venous congestion as assessed by the venous excess ultrasound (VExUS) score in hospitalized patients with acute heart failure (HF). METHODS: Consecutive patients admitted for acute HF were prospectively enrolled. Inferior vena cava diameter, hepatic vein, portal vein, and renal vein Doppler waveforms were assessed at admission, and patients were stratified based on VExUS score from 0 to 3, with higher values indicating worse congestion. The clinical score Get with the Guidelines (GWTG)-HF for predicting in-hospital mortality in HF was evaluated. In-hospital mortality was recorded. RESULTS: Two hundred ninety patients admitted with acute HF were included, and 114 (39%) of them were classified as VExUS score 3, which was the most prevalent group. Patients with VExUS score 3 suffered more frequently from chronic atrial fibrillation, chronic kidney disease, and anemia. Parameters independently associated with VExUS score 3 were higher mean E/e' ratio, larger right ventricular size, severe tricuspid regurgitation, and impaired right atrial function. A VExUS score of 3 was associated with in-hospital mortality (odds ratio, 8.03; 95% CI [2.25-28.61], P = .001). The addition of VExUS score on top of the GWTG-HF score improved the predictability of the model (Δx2 = +8.44, P = .03) for in-hospital mortality, whereas other indices of venous congestion (right atrial function, inferior vena cava size) did not. CONCLUSIONS: Patients admitted with acute HF commonly had severe venous congestion based on the VExUS score. The VExUS score improved the prediction of in-hospital mortality compared with other indices of venous congestion.

The prognostic impact of right ventricular-pulmonary arterial coupling in heart failure: a systematic review and meta-analysis.

The echocardiographic tricuspid annular plane systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP) ratio is a non-invasive surrogate of right ventricular-pulmonary arterial (RV-PA) coupling which corresponds well with the respective invasively derived index. Recently, a wealth of observational data has arisen, outlining its prognostic value in heart failure (HF) patients. To systematically appraise and quantitatively synthesize the evidence of the prognostic value of TAPSE/PASP ratio in left-sided HF regardless of etiology or left ventricular ejection fraction. A systematic literature review was conducted in electronic databases to identify studies reporting the association of TAPSE/PASP ratio with outcomes in patients with HF and, when appropriate, a random-effects meta-analysis was conducted to quantify the unadjusted and adjusted hazard ratios [(a)HRs] for all-cause death and the composite outcome of all-cause death or HF hospitalization. Eighteen studies were deemed eligible encompassing 8,699 HF patients. The applied cut-off value for RV-PA uncoupling varied substantially from 0.27 to 0.58 mm/mmHg, and in most studies values lower than the applied cutoff conveyed dismal prognosis. Eleven studies reported appropriate data for meta-analysis. TAPSE/PASP reduction by 1 mm/mmHg was independently associated with all-cause death (pooled aHR=1.32 [1.06-1.65]; p=0.01; I2=56%) and the composite outcome (pooled aHR=3.48 [1.67-7.25]; p<0.001; I2=0%). When a TAPSE/PASP cutoff value of 0.36 mm/mmHg was applied it yielded independent association with all-cause death (pooled aHR=2.84 [2.22-3.64]; p<0.001; I2=82%). RV-PA coupling assessed by echocardiographic TAPSE/PASP ratio appears to be an independent outcome predictor for HF patients.

Periostin is overexpressed, correlated with fibrosis and differs among grades of cardiomyocyte hypertrophy in myectomy tissue of patients with hypertrophic cardiomyopathy.

Periostin, a secreted matricellular protein, has been implicated in cardiac extracellular matrix remodeling and fibrosis. Evidence suggest that periostin stimulates cardiomyocyte hypertrophy. The current study aims to investigate the extent of periostin expression in patients with advanced Hypertrophic Cardiomyopathy (HCM) and its correlation with fibrosis and hallmark histopathological features of the disease. Interventricular septal tissue from thirty-nine HCM patients who underwent myectomy and five controls who died from non-cardiac causes was obtained. Staining with Masson's Trichrome and immunohistochemistry were used to localize fibrosis and periostin respectively. The extent of fibrosis and the expression of periostin were defined as the stained percentage of total tissue area using digital pathology software. Periostin expression was higher in HCM patients compared to controls (p<0.0001), positively correlated with the extent of fibrosis (r = 0.82, p<0.001), positively correlated with maximal interventricular septal thickness (Rho = 0.33, p = 0.04) and negatively correlated with LVEF (r = -0.416, p = 0.009). Periostin was approximately co-localized with fibrosis. Mean periostin expression was lower in patients with mild grade cardiomyocyte hypertrophy compared to those with moderate grade (p = 0.049) and lower in patients with mild grade replacement fibrosis compared to moderate grade (p = 0.036). In conclusion, periostin is overexpressed in advanced HCM, correlated with fibrosis and possibly related to cardiomyocyte hypertrophy.

Oral Anticoagulation in Patients With Atrial High-Rate Episodes: Focus on Clinical Implications.

Background Although previous studies showed that atrial high-rate episodes (AHREs) are associated with a higher risk of developing incident atrial fibrillation (AF) and thromboembolic events, their clinical significance is still unclear. The purpose of this study was to define whether there is any clinical impact on the occurrence of ischemic and hemorrhagic events in patients with AHREs and initiation of oral anticoagulation (OAC). Methodology Patients with AHREs who had received cardiac implantable electronic devices (CIEDs, i.e., dual-chamber pacemaker [PM] or implantable cardioverter defibrillator [ICD]) were included in the study. OAC initiation was decided by the assistant doctor. Patients who received OACs comprised the OAC group, while patients who were not referred for OAC initiation were included in the control group. The primary endpoint was the time to the event of the occurrence of thromboembolic events (thromboembolic event-free survival). Results A total of 154 individuals (77 in each group) were enrolled in the study, with a mean age of 72.5 years. The mean follow-up period for the OAC group was 19.1 months and for the control group, 18.9 months (P = 0.9). Thromboembolic events were noticed only in seven patients. Six of them were in the control group, and only one in the OAC group (P = 0.05). Major bleeding events were noticed in five patients, one of whom was in the control group and the rest in the OAC group (P = 0.17). Conclusions OAC therapy in patients with AHREs was not associated with a significant difference in the risk of thromboembolic and bleeding events. Baseline patient characteristics and AHRE duration may be useful to intensify the monitoring and management of patients with AHREs. Bleeding events may be indicators of cancer in patients with AHREs receiving OACs.

Differences in Demographics, in-Hospital Management and Short-Term Prognosis in Admissions for Acutely Decompensated Heart Failure to Cardiology vs. Internal Medicine Departments: A Prospective Study.

Heart failure (HF) is among the leading causes of unplanned hospital admissions worldwide. Patients with HF carry a high burden of comorbidities; hence, they are frequently admitted for non-cardiac conditions and managed in Internal Medicine Departments (IMD). The aim of our study was to investigate differences in demographics, in-hospital management, and short-term outcomes of HF patients admitted to IMD vs. cardiology departments (CD). A prospective cohort study enrolling consecutive patients with acutely decompensated HF either as primary or as secondary diagnosis during the index hospitalization was conducted. Our primary endpoint was a combined endpoint of in-hospital mortality and 30-day rehospitalization for HF. A total of 302 patients participated in the study, with 45% of them admitted to IMD. Patients managed by internists were older with less pronounced HF symptoms on admission. In-hospital mortality was higher for patients admitted to IMD vs. CD (21% vs. 6%, p < 0.001). The composite endpoint of in-hospital death and heart failure hospitalizations at 30 days post-discharge was higher for patients admitted to IMD both in univariate [OR: 3.2, 95% CI (1.8-5.7); p < 0.001] and in multivariate analysis [OR 3.74, 95% CI (1.72-8.12); p = 0.001]. In addition, the HF rehospitalization rate at 6 months after discharge was higher in IMD patients [HR 1.65, 95% CI (1.1, 2.4), p = 0.01]. Overall, HF patients admitted to IMD have worse short-term outcomes compared to patients admitted to CD.

Quantitative Late Gadolinium Enhancement Cardiac Magnetic Resonance and Sudden Death in Hypertrophic Cardiomyopathy: A Meta-Analysis.

BACKGROUND: Quantitative late gadolinium enhancement (LGE) cardiac magnetic resonance provides important prognostic information for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM). However, it has not been fully integrated into clinical practice. OBJECTIVES: To assess the prognostic value of LGE extent in predicting SCD in adults with HCM across different methods of quantification, thresholds, and patients' clinical profile. METHODS: The authors searched PubMed, Web of Science, and Cochrane Library for studies investigating the prognostic value of LGE% in predicting SCD in HCM. Pooled odds ratios were calculated with 95% CIs. The optimal threshold was determined using a multiple cutoffs model. RESULTS: Eleven studies were included in the meta-analysis with a total of 5,550 patients and a median follow-up time of 5.2 years. Two studies quantified LGE manually, 7 studies used the 6 SD technique, 1 study used the 4 SD technique, and 1 study the 2 SD technique. There was no statistically significant difference in predicting SCD between these 4 methods (P = 0.443). Optimal cutoff could be determined only for the 6 SD technique. LGE 10% was the optimal threshold of the 6 SD technique with sensitivity 0.73 and specificity 0.67. CONCLUSIONS: The different LGE quantification techniques have comparable accuracy in predicting SCD. When the more extensively studied 6 SD technique is used, LGE 10% is the optimal cutoff and can effectively restratify intermediate-risk patients. LGE extent can improve HCM risk stratification, but it is unlikely to become a standalone tool.

Apical Hypertrophic Cardiomyopathy: Diagnosis, Natural History, and Management.

Apical hypertrophic cardiomyopathy (ApHCM) represents a rare variant of hypertrophic cardiomyopathy (HCM) with distinct phenotypic characteristics. The prevalence of this variant varies according to each study's geographic region. The leading imaging modality for the diagnosis of ApHCM is echocardiography. Cardiac magnetic resonance, however, is the gold standard for ApHCM diagnosis in case of poor acoustic windows or equivocal echocardiographic findings but also in cases of suspected apical aneurysms. The prognosis of ApHCM was reported to be relatively benign, although more recent studies seem to contradict this, demonstrating similar incidence of adverse events compared with the general HCM population. The aim of this review is to summarize the available evidence for the diagnosis of ApHCM, highlight distinctions in comparison to more frequent forms of HCM with regards to its natural history, prognosis, and management strategies.

Transcatheter closure of atrial septal defect in the elderly: a systematic review and meta-analysis.

OBJECTIVE: Despite the establishment of transcatheter closure as the treatment of choice in adults with secundum atrial septal defects (ASDs), the effectiveness of this approach in the elderly is disputed. This systematic review and meta-analysis aims to explore the impact of transcatheter ASD closure in patients ≥60 years old. METHODS: We systematically searched four major electronic databases (PubMed, CENTRAL (Cochrane Central Register of Controlled Trials), Scopus and Web of Science), ClinicalTrials.gov, article references and grey literature. Primary outcomes were the right ventricular end-diastolic diameter (RVEDD) and the New York Heart Association functional class change, whereas secondary outcomes included systolic pulmonary arterial pressure (sPAP), left ventricular end-diastolic diameter (LVEDD), brain natriuretic peptide (BNP), tricuspid valve regurgitation (TR) change, as well as the rate of atrial arrhythmias and all-cause mortality. RESULTS: In total, 18 single-arm cohorts comprising 1184 patients were included. RVEDD was reduced after ASD closure (standardised mean difference (SMD) -0.9, 95% CI -1.2 to -0.7). Elderly patients had 9.5 times higher odds of being asymptomatic after ASD closure (95% CI 5.06 to 17.79). Furthermore, ASD closure improved sPAP (mean difference (MD) -10.8, 95% CI -14.6 to -7), LVEDD (SMD 0.8, 95% CI 0.7 to 1.0), TR severity (OR 0.39, 95% CI 0.25 to 0.60) and BNP (MD -68.3, 95% CI -114.4 to -22.1). There was a neutral effect of ASD closure on atrial arrhythmias. CONCLUSIONS: Transcatheter ASD closure is beneficial for the elderly population since it improves functional capacity, biventricular dimensions, pulmonary pressures, TR severity and BNP. However, the incidence of atrial arrhythmias did not change significantly after the intervention. PROSPERO REGISTRATION NUMBER: CRD42022378574.

The patient pathway in ATTR-CM in Greece and how to improve it: A multidisciplinary perspective.

Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed disease associated with high mortality rates and the patient journey is characterized by increased complexities. Accurate and timely diagnosis and prompt initiation of disease-modifying treatment constitute the contemporary unmet need in ATTR-CM. ATTR-CM diagnosis is characterized by considerable delays and high rates of misdiagnosis. The majority of patients present themselves to primary care physicians, internists, and cardiologists, and many have undergone repeated medical evaluations before an accurate diagnosis has been made. The disease is diagnosed mainly after the development of heart failure symptoms, reflecting a long course of missed opportunities before diagnosis and disease-modifying treatment initiation. Early referral to experienced centers ensures prompt diagnosis and therapy. Early diagnosis, better care coordination, acceleration of digital transformation and reference networks, encouragement of patient engagement, and implementation of rare disease registries are the key pillars to improve the ATTR-CM patient pathway and achieve important benefits in ATTR-CM outcomes.

Clinical Value of Novel Echocardiographic Biomarkers Assessing Myocardial Work in Acute Heart Failure-Rationale and Design of the "Beyond Myo-HF Study".

BACKGROUND: Despite ongoing treatment advancements in chronic heart failure (HF), mortality and readmission rates remain high for patients hospitalized for decompensated acute HF. These patients represent a distinct HF group, which requires emergent echocardiographic evaluation in an attempt to provide optimal and individualized acute care. The role of serial advanced echocardiographic assessment in acute HF for risk stratification and treatment guidance has not been thoroughly explored. METHODS: The "Beyond Myo-HF Study" is a prospective, non-interventional cohort trial designed to enroll acutely admitted patients with symptoms and/or signs of HF. The aim of this study is to investigate whether intrahospital changes of conventional and novel echocardiographic indices of myocardial function and congestion-related markers can predict early mortality, late mortality, and HF rehospitalization. As per the protocol, all patients undergo a pair of state-of-the-art echocardiographic assessments, with a rigorous protocol including speckle tracking analysis of all cardiac chambers and myocardial work analysis for the left and right ventricle, upon admission and pre-discharge. Their laboratory profile is captured at those two time-points, and their therapeutic management is recorded. Patients will be followed-up for a median period of 12 months after enrollment. CONCLUSIONS: The "Beyond Myo-HF" study is an ongoing, prospective trial aspiring to provide deep insight into the pathophysiology of acute HF, to enlighten the reverse cardiac functional and anatomical remodeling during hospitalization, and to recognize echocardiographic patterns capable of predicting adverse outcomes during and post decompensation of acute HF.

Prevalence, characteristics, and natural history of apical phenotype in a large cohort of patients with hypertrophic cardiomyopathy.

BACKGROUND: Apical hypertrophic cardiomyopathy (ApHCM) is a variant of hypertrophic cardiomyopathy (HCM) with distinct imaging and clinical characteristics. Data on the prognosis of this HCM subgroup appear conflicting. Our study aims to clarify the natural history of ApHCM and identify predictors of outcomes. MATERIALS AND METHODS: A total of 856 patients with HCM were retrospectively examined. ApHCM was defined as asymmetric left ventricular hypertrophy confined predominantly at the apex, either isolated (pure ApHCM type) or with co-existent hypertrophy of the interventricular septum (mixed ApHCM). Echocardiographic, clinical, and survival data were compared between individuals with ApHCM and non-ApHCM. RESULTS: A total of 143 (16.7%) patients were diagnosed with ApHCM. Compared with non-ApHCM, subjects with apical HCM were diagnosed at an older age and had better echocardiographic indices and more comorbidities at baseline. Apical aneurysms were more prevalent among the ApHCM phenotype (6.3% vs. 1.7%, p = 0.003). During a mean follow-up of 6 ± 3 years, ApHCM was characterized by lower all-cause, cardiovascular, heart failure-related mortality, and ventricular arrhythmic events compared with non-ApHCM. Multivariate analysis identified atrial fibrillation and HCM risk-sudden cardiac death (SCD) as independent predictors of the composite outcome of overall mortality and hospitalizations for cardiovascular reasons (hazard ratio [HR] 4.3, 95% confidence interval [CI] 1.9-9.5 for atrial fibrillation and HR 1.2, 95% CI 1.02-1.3 for HCM risk-SCD) in ApHCM. CONCLUSIONS: ApHCM exhibited a lower rate of all-cause mortality and arrhythmic events in the middle-aged population of patients with HCM. Atrial fibrillation and HCM risk-sudden cardiac death were independent predictors of a composite of overall mortality and cardiovascular hospitalizations among those with ApHCM.

Iron therapy and severe arrhythmias in HFrEF: rationale, study design, and baseline results of the RESAFE-HF trial.

AIMS: The Iron Intravenous Therapy in Reducing the burden of Severe Arrhythmias in HFrEF (RESAFE-HF) registry study aims to provide real-word evidence on the impact of intravenous ferric carboxymaltose (FCM) on the arrhythmic burden of patients with heart failure with reduced ejection fraction (HFrEF), iron deficiency (ID), and implanted cardiac implantable electronic devices (CIEDs). METHODS AND RESULTS: The RESAFE-HF (NCT04974021) study was designed as a prospective, single-centre, and open-label registry study with baseline, 3, 6, and 12 month visits. Adult patients with HFrEF and CIEDs scheduled to receive IV FCM as treatment for ID as part of clinical practice were eligible to participate. The primary endpoint is the composite iron-related endpoint of haemoglobin ≥ 12 g/dL, ferritin ≥ 50 ng/L, and transferrin saturation > 20%. Secondary endpoints include unplanned HF-related hospitalizations, ventricular tachyarrhythmias detected by CIEDs and Holter monitors, echocardiographic markers, functional status (VO2 max and 6 min walk test), blood biomarkers, and quality of life. In total, 106 patients with a median age of 72 years (14.4) were included. The majority were male (84.9%), whereas 92.5% of patients were categorized to New York Heart Association II/III. Patients' arrhythmic burden prior to FCM administration was significant-19 patients (17.9%) received appropriate CIED therapy for termination of ventricular tachyarrhythmia in the preceding 12 months, and 75.5% of patients have frequent, repetitive multiform premature ventricular contractions. CONCLUSIONS: The RESAFE-HF trial is expected to provide evidence on the effect of treating ID with FCM in HFrEF based on real-world data. Special focus will be given on the arrhythmic burden post-FCM administration.

Prescription Rates and Prognostic Implications of Optimally Targeted Guideline-Directed Medical Treatment in Heart Failure and Atrial Fibrillation: Insights From The MISOAC-AF Trial.

ABSTRACT: Heart failure (HF) and atrial fibrillation (AF) commonly coexist in real-life clinical practice. Among patients with HF with reduced ejection fraction (HFrEF) or HF with mildly reduced ejection fraction (HFmrEF), guidelines call for evidence-based target doses of renin-angiotensin-aldosterone system inhibitors and beta-blockers. However, target doses of guideline-directed medical treatment (GDMT) are often underused in real-world conditions, including HF-AF comorbidity. This retrospective cohort study of a randomized trial (Motivational Interviewing to Support Oral AntiCoagulation adherence in patients with nonvalvular AF) included hospitalized patients with AF and HFrEF or HFmrEF. Optimally targeted GDMT was defined as intake of evidence-based target doses of renin-angiotensin-aldosterone system and beta-blockers at 3 months after discharge. Rates of optimally targeted GDMT achievement across the baseline estimated glomerular filtration rate (eGFR) were assessed. Independent predictors of nontargeted GDMT and its association with all-cause mortality and the composite of cardiovascular death or HF hospitalization were assessed by regression analyses. In total, 374 patients with AF and HFrEF or HFmrEF were studied. At 3 months after discharge, 30.7% received target doses of GDMT medications. The rate of optimally targeted GDMT was reduced by 11% for every 10 mg/min/1.73 m 2 decrease in baseline eGFR [adjusted ß = 0.99; 95% confidence interval (CI), 0.98-0.99] levels. After a median 31-month follow-up period, 37.8% patients in the optimally targeted GDMT group died, as compared with 67.8% (adjusted hazard ratio: 1.49; 95% CI, 1.05-2.13) in the nontargeted GDMT group. The risk of cardiovascular death or HF hospitalization was also higher in these patients (adjusted hazard ratio: 1.60; 95% CI, 1.17-2.20). Target doses of all HF drugs were reached in roughly one-third of patients with AF and HFrEF or HFmrEF 3 months after hospital discharge. Nontargeted GDMT was more frequent across lower eGFR levels and was associated with worse outcomes.

Left Atrial Myopathy is Associated With Exercise Incapacity and Ventilatory Inefficiency in Hypertrophic Cardiomyopathy.

BACKGROUND: Left atrial (LA) myopathy is an established component of hypertrophic cardiomyopathy (HCM); however, the data about its association with exercise incapacity or ventilatory inefficiency that may be seen in HCM patients are limited. This study aimed to explore the association between LA myopathy, evaluated by echocardiography LA strain, and exercise capacity and ventilatory efficiency, evaluated by cardiopulmonary exercise testing (CPET), in HCM patients. METHODS: This study included 241 consecutive HCM patients (aged 51.2±15.7 years 67.2% male) in sinus rhythm who underwent CPET and transthoracic echocardiography at the same visit. Exercise incapacity (maximal/predicted oxygen consumption [%peakVO2] <80%) and ventilatory inefficiency (ventilation/carbon dioxide output [VE/VCO2] slope >34) were assessed by CPET. Left atrial myopathy was examined by speckle-tracking myocardial deformation parameters: LA reservoir, conduit and booster strain. RESULTS: All three LA strain values were univariate predictors of exercise capacity and ventilatory efficiency. Among them, LA reservoir strain had the higher r correlation coefficient for predicting both %peakVO2 and VE/VCO2 slope. Left atrial reservoir strain, presence of angina and family history of HCM were independent predictors of exercise capacity. Left atrial reservoir strain, male gender and non-sustained ventricular tachycardia were independent predictors of ventilatory efficiency. Left atrial reservoir strain was a significant predictor of %peakVO2<80% with an optimal cut-off value of 27% (sensitivity 87% and specificity 31%) and VE/VCO2>34 with an optimal cut-off value of 18% (sensitivity 71% and specificity 83%). CONCLUSION: Left atrial myopathy, as reflected by the LA strain values, was associated with exercise incapacity and ventilatory inefficiency in HCM individuals. Left atrial reservoir strain was the only common independent predictor of %peakVO2 and VE/VCO2 slope.

Wild-Type Transthyretin Amyloid Cardiomyopathy: The Gordian-Knot of Novel Therapeutic Regimens.

Wild-type TTR amyloidosis (wtATTR) represents a disease difficult to diagnose with poor prognosis. Increased clinical suspicion is key, allowing for timely diagnosis. Until recently, only off-label therapies were available but recent introduction of disease specific therapy has shown potential to alter the natural history of the disease. Tafamidis, the only currently approved drug for the therapy of wtATTR, provided significantly better survival and quality of life. However, not all subgroups of patients derived equal benefit. This, along with the increased cost of treatment raised question on whether treatment should be invariably administered through the wtATTR population. This review aims to summarize current evidence on the natural history and staging systems for wtATTR, as well as available treatment options. Special consideration is given to the selection process of patients who would be expected to gain maximum benefit from tafamidis treatment, based on an ethical and cost-effective point of view.