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The evaluation of left ventricular (dys)function is at the core of clinical cardiology practice in patients with hypertrophic cardiomyopathy. Hypertrophic cardiomyopathy proceeds along paradigms that are profoundly different and follows disease-specific patterns of progression towards heart failure. By automatically applying a standard approach, much information is lost or misplaced, and severe degrees of dysfunction may be erroneously interpreted as mild by such an assumption. This is mostly evident during the assessment of systolic function, in which a superficial evaluation of standard variables, often relatively preserved (even in advanced stages), may lead to underestimation of clinical severity, with potential consequences, such as late referral for transplantation. Currently, specific biomarkers-particularly N-terminal prohormone of B-type natriuretic peptide and high-sensitivity cardiac troponin I-play a key role in the diagnosis, treatment and risk stratification of hypertrophic cardiomyopathy. Elevated biomarkers seem to depict patients with more severe disease, adding diagnostic and prognostic information to conventional assessments, such as left ventricular ejection fraction, New York Heart Association class and left ventricular outflow tract obstruction. For all these reasons, we provide a review of current knowledge on systo-diastolic function in patients with hypertrophic cardiomyopathy, in an attempt to define clinically significant degrees of dysfunction, biomarker status and specific "red alert" thresholds in clinical practice.

Background Despite hypertrophic cardiomyopathy (HCM) being the most common inherited heart disease and conferring increased risk for heart failure (HF) and sudden cardiac death (SCD), risk assessment in HCM patients is still largely unresolved. Objective To synthesize and compare the prognostic impact of demographic, clinical, biochemical, and imaging findings in patients with HCM. Methods We searched PubMed, Embase, and Cochrane Library for studies published from inception to November 2020, and the endpoints were: i) all-cause death; ii) an arrhythmic endpoint including SCD, sustained ventricular tachycardia, ventricular fibrillation, or aborted SCD; iii) a composite endpoint including i) or ii) plus hospitalization for HF or cardiac transplantation. We performed a pairwise meta-analysis obtaining the pooled estimate separately for the association between baseline variables and study endpoints. A random-effects network meta-analysis (NMA) was subsequently used to comparatively assess the prognostic value of outcome predictors. Results One-hundred-eleven studies with 56,792 HCM patients were included. Among others, increased BNP/NT-proBNP, late-gadolinium-enhancement (LGE), positive genotype, impaired global longitudinal strain and presence of apical aneurysm conferred increased risk for the composite endpoint. At NMA, LGE showed the highest prognostic value for all endpoints and was superior to all other predictors except NYHA class≥II. A multiparametric imaging-based model was superior in predicting the composite endpoint compared to a pre-specified model based on conventional risk factors. Conclusions This network meta-analysis supports the development of multiparametric risk prediction algorithms, including advanced imaging markers additively to conventional risk factors, for refined risk stratification in HCM.

Background Bicuspid aortic valve (BAV) is the most frequent congenital valve disease in adults. It is often associated with other congenital cardiac defects. Sometimes it is associated with aortic dilatation. BAV is an heterogeneous disease with varying valve morphology (asymmetrical cusp size and rafe), annulus geometry and size, asymmetrical calcification of the aortic valve and left ventricular outflow tract. Case Report A 32 year-old male patient was diagnosed with bicuspid aortic valve after several cardiologic visits for eligibility to competitive sport. Since April 2021 he developed a progressive exertional dyspnea for strenuous efforts. In February 2022, he was referred to our department after a Holter ECG showed a bradyarrhythmia with complete atrioventricular block. The echocardiography evaluation demonstrated a preserved ejection fraction and a bicuspid aortic valve with a mild-moderate regurgitation. The coronary computed tomography showed a thick and calcified bicuspid aortic valve with a coarse calcification of the anterior cuspid that involve the pars membranacea of the interventricular septum. The ergometric exercise demonstrated chronotropy incompetence. The tomography confirmed the mildy aortic root dilatation. Therefore, an MRI was performed and reported a small laminar LGE on the infero-lateral wall of the left ventricle, of unclear significance. He underwent Dual-Chamber permanent pacemaker implantation. A conservative approach was preferred over valvular replacement, considering the mild aortic root dilatation on a background of mild-to- moderate aortic insufficiency. Conclusion Our case is unusual given the bicuspid aortic valve concomitant with atrioventricular block, which was connected with the location of the calcification. Thus, the aim of our case report is, to describe a complication to this condition which, although rare, represents a different clinical presentation of the pathology itself in a young adult.

Purpose: To characterize the genetic architecture of left ventricular noncompaction (LVNC) and investigate the extent to which it may represent a distinct pathology or a secondary phenotype associated with other cardiac diseases. Methods: We performed rare variant association analysis with 840 LVNC cases and 125,748 gnomAD population controls, and compared results to similar analyses on dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). Results: We observed substantial genetic overlap indicating that LVNC often represents a phenotypic variation of DCM or HCM. In contrast, truncating variants in MYH7, ACTN2, and PRDM16 were uniquely associated with LVNC and may reflect a distinct LVNC etiology. In particular, MYH7 truncating variants (MYH7tv), generally considered nonpathogenic for cardiomyopathies, were 20-fold enriched in LVNC cases over controls. MYH7tv heterozygotes identified in the UK Biobank and healthy volunteer cohorts also displayed significantly greater noncompaction compared with matched controls. RYR2 exon deletions and HCN4 transmembrane variants were also enriched in LVNC, supporting prior reports of association with arrhythmogenic LVNC phenotypes. Conclusion: LVNC is characterized by substantial genetic overlap with DCM/HCM but is also associated with distinct noncompaction and arrhythmia etiologies. These results will enable enhanced application of LVNC genetic testing and help to distinguish pathological from physiological noncompaction.

Background Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis. Cardiac specific involvement (CSI) is caused by coronary artery vasculitis, but also by myocardial eosinophilic infiltration. To date, the prevalence of CSI associated with EGPA is unresolved. Aim of this study was to systematically assess the prevalence and clinical impact of CSI in a consecutive outpatient EGPA population. Methods Between October 2018 and July 2019, we prospectively enrolled 52 consecutive EGPA patients. All underwent comprehensive evaluation including a standardized questionnaire, physical examination, 12-lead-ECG, echocardiography. Cardiac magnetic resonance and 24 h-Holter were performed as deemed clinically appropriate. Cardiac abnormalities were defined as CSI based on the likelihood of their relation to EGPA vasculitis, after exclusion of alternative diagnoses. Results 52 enrolled patients, mean age 59±1 years. Thirteen of the 52 patients (25%) were classified as CSI+. CSI was characterized by myocarditis in four patients, non-scar-related regional wall motions abnormalities (RWMA) in three, apical thrombosis in two (one also had RWMA), pericarditis in three and non-atherosclerotic coronary disease (Prinzmetal angina and coronaritis) in 2. Five (38%) of the 13 CSI+ patients, presented an apical aneurysm. Peak eosinophil count at diagnosis was higher in CSI+: 8000 /μl vs CSI-: 3000 /μl, p = 0.017. Overall, 2 patients had severe LV dysfunction, 5 required urgent hospitalization and 8 required long-term cardioactive therapy. Conclusions CSI was present in one-quarter of patients, often associated with high peak eosinophils. Myocarditis, RWMA and apical aneurysms were the most common manifestations. Although rarely severe and life-threatening, CSI often required long-term cardioactive treatment.

Purpose: Pulmonary arterial hypertension (PAH), documented in a significant portion of hypertrophic cardiomyopathy (HCM) patients, has been shown to adversely impact prognosis. In most HCM patients congestive symptoms are consistently elicited by exercise, thus suggesting the need for a provocative test to assess cardiac hemodynamics during effort. Combining cardiopulmonary exercise test (CPET) with echocardiography, we aimed to evaluate the presence of exercise induced pulmonary arterial hypertension (EiPAH), its role in functional limitation and its prognostic significance in a cohort of patients with obstructive and non-obstructive HCM.Methods: study population included 182 HCM patients evaluated combining CPET and stress echocardiography. Left-ventricular outflow tract (LVOT) velocities, trans-tricuspid gradient, and cardiopulmonary variables were continuously measured. Results: Thirty-seven patients (20%) developed EiPAH, defined as systolic pulmonary arterial pressure (sPAP)>40 mmHg during exercise. EiPAH was associated with lower exercise performance, larger left atrial volumes, higher LVOT gradient and higher VE/VCO2 slope. At multivariable analysis baseline sPAP (pConclusion: EiPAH was present in about one fifth of HCM patients without evidence of elevated pulmonary pressures at rest and was associated with adverse clinical outcome. Diagnosing EiPAH by exercise echocardiography/CPET may help physicians to detect early stage of PAH thus allowing a closer clinical monitoring and individualized therapies

Heart Failure (HF) in elderly patients is a systemic syndrome where advanced age, comorbidities with organ system deterioration, frailty and impaired cognition significantly impact outcome. Cardiac cachexia, sarcopenia and frailty despite overlap in definitions are different clinical entities that frequently coexist in HF patients. However, these co-factors often remain unaddressed, resulting in poor quality-of-life, prolonged physical disability and exercise intolerance and finally with higher rehospitalization rates and mortality. Strategy aim to increase muscle mass and muscle strength and delay the occurrence of frailty state appear essential in this regard. Common HF drugs therapy (b-blockers, angiotensin-converting enzyme inhibitors) and prescription of physical exercise program remain the cornerstone of therapeutic approach in HF patients with new promising data regarding nutritional supplementation. However, the treatment of all these conditions still remain debated and only a profound knowledge of the specific mechanisms and patterns of disease progression will allow to use the appropriate therapy in a given clinical setting. For all these reasons we briefly review current knowledge on frailty, sarcopenia and cachexia in HF patients with the attempt to define clinically significant degrees of multiorgan dysfunction, specific "red alert" thresholds in clinical practice and therapeutic approach.

Despite numerous studies assessing the natural history of patients with hypertrophic cardiomyopathy (HCM), there is lack of data regarding the burden of hospitalization. Aim of this study was to describe prevalence, causes and predictors of cardiovascular hospitalization in patients with HCM.We retrospectively included 253 patients with HCM undergoing first evaluation at our center. Enrolment criteria included cardiac magnetic resonance imaging (CMRI) at baseline and 1-year follow-up. All hospital admissions were recorded during follow-up and adjudicated as acute vs elective and cardiovascular (CV) vs non-cardiovascular (non-CV).During 6.4 ± 4.0 years there were 187 hospitalizations in 92 patients (36%, at a rate of 5.7%/year). Most were CV-related (158/187,84.5%; 4.8%/year) while non-CV admissions were 29/187 (15.5%, 0.88%/year). There was a slight predominance of elective (n = 96, 58%, 2.8%/year) vs acute (n = 62, 41.8%, 2.0%/year) CV hospitalizations. Independent predictors of CV hospitalization were baseline symptoms (NYHA class II vs I: HR 2.06; 95% CI 1.24-3.43, NYHA III-IV vs I: HR 3.05; 95% CI 1.40-6.65, p = .004), indexed left atrial (LA) volume (HR 1.03; 95% CI 1.01-1.04, p .001), and lower indexed right ventricular end-diastolic volume iRVEDV) at cardiac magnetic resonance (HR 0.99; 95% CI 0.97-0.99, p = .03).In little over 6 years, CV hospitalization was required in over one-in-three of our HCM patients, often unplanned and due to acute disease-related complications. Symptomatic status, larger LA volume and reduced iRVEDV at baseline were independently associated with CV admissions. Strategies aimed at preventing hospitalizations are an important target to reduce the burden of disease in HCM patients.

Despite hypertrophic cardiomyopathy (HCM) being the most common inherited heart disease and conferring increased risk for heart failure (HF) and sudden cardiac death (SCD), risk assessment in HCM patients is still largely unresolved.This study aims to synthesize and compare the prognostic impact of demographic, clinical, biochemical, and imaging findings in patients with HCM.The authors searched PubMed, Embase, and Cochrane Library for studies published from 1955 to November 2020, and the endpoints were: 1) all-cause death; 2) an arrhythmic endpoint including SCD, sustained ventricular tachycardia, ventricular fibrillation, or aborted SCD; and 3) a composite endpoint including (1) or (2) plus hospitalization for HF or cardiac transplantation. The authors performed a pairwise meta-analysis obtaining the pooled estimate separately for the association between baseline variables and study endpoints. A random-effects network meta-analysis was subsequently used to comparatively assess the prognostic value of outcome associates.A total of 112 studies with 58,732 HCM patients were included. Among others, increased brain natriuretic peptide/N-terminal pro-B-type natriuretic peptide, late gadolinium enhancement (LGE), positive genotype, impaired global longitudinal strain, and presence of apical aneurysm conferred increased risk for the composite endpoint. At network meta-analysis, LGE showed the highest prognostic value for all endpoints and was superior to all other associates except New York Heart Association functional classclass II. A multiparametric imaging-based model was superior in predicting the composite endpoint compared to a prespecified model based on conventional risk factors.This network meta-analysis supports the development of multiparametric risk prediction algorithms, including advanced imaging markers additively to conventional risk factors, for refined risk stratification in HCM. (Long-term prognosis of hypertrophic cardiomyopathy according to genetic, clinical, biochemical and imaging findings: a systemic review and meta-analysis; CRD42020185219).

Epicardial adipose tissue (EAT) is an endocrine and paracrine organ constituted by a layer of adipose tissue directly located between the myocardium and visceral pericardium. Under physiological conditions, EAT exerts protective effects of brown-like fat characteristics, metabolizing excess fatty acids, and secreting anti-inflammatory and anti-fibrotic cytokines. In certain pathological conditions, EAT acquires a proatherogenic transcriptional profile resulting in increased synthesis of biologically active adipocytokines with proinflammatory properties, promoting oxidative stress, and finally causing endothelial damage. The role of EAT in heart failure (HF) has been mainly limited to HF with preserved ejection fraction (HFpEF) and related to the HFpEF obese phenotype. In HFpEF, EAT seems to acquire a proinflammatory profile and higher EAT values have been related to worse outcomes. Less data are available about the role of EAT in HF with reduced ejection fraction (HFrEF). Conversely, in HFrEF, EAT seems to play a nutritive role and lower values may correspond to the expression of a catabolic, adverse phenotype. As of now, there is evidence that the beneficial systemic cardiovascular effects of sodium-glucose cotransporter-2 receptors-inhibitors (SGLT2-i) might be partially mediated by inducing favorable modifications on EAT. As such, EAT may represent a promising target organ for the development of new drugs to improve cardiovascular prognosis. Thus, an approach based on detailed phenotyping of cardiac structural alterations and distinctive biomolecular pathways may change the current scenario, leading towards a precision medicine model with specific therapeutic targets considering different individual profiles. The aim of this review is to summarize the current knowledge about the biomolecular pathway of EAT in HF across the whole spectrum of ejection fraction, and to describe the potential of EAT as a therapeutic target in HF.

Congestion is the main cause of hospitalization in patients with acute heart failure (AHF), however its precise assessment by simple clinical evaluation remains elusive. The recent introduction of the lung ultrasound scan (LUS) allowed to physicians to more precisely quantify pulmonary congestion. The aim of this study was to compare clinical congestion (CC) with LUS and B-type natriuretic peptide (BNP) in order to achieve a more complete evaluation and to evaluate the prognostic power of each measurement. Methods: All patients were submitted to clinical evaluation for blood sample analysis and LUS at admission and before discharge. LUS protocol evaluated the number of B-lines for each chest zone by standardized eight site protocol. CC was measured following ESC criteria. The mean difference between admission and discharge congestion logBNP and B-lines values were calculated. Combined end points of death and rehospitalization was calculated over 180 days. Results: 213 patients were included in the protocol; 133 experienced heart failure with reduced ejection fraction (HFrEF), and 83 presented with heart failure with preserved ejection fraction (HFpEF). Patients with HFrEF had a more increased level of BNP (1150 (812–1790) vs. 851 (694–1196); p = 0.002) and B lines total number (32 (27–38) vs. 30 (25–36); p = 0.05). A positive correlation was found between log BNP and Blines number in both HFrEF (r = 0.57; p < 0.001) and HFpEF (r = 0.36; p = 0.001). Similarly, dividing B-lines among tertiles the upper group (B-lines ≥ 36) had an increased clinical congestion score. Among three variables at admission only B-lines were predictive for outcome (AUC 0.68 p < 0.001) but not LogBNP and CC score. During 180 days of follow-up, univariate analysis showed that persistent ΔB-lines

Aims Pulmonary arterial hypertension (PAH) has been described in patients with hypertrophic cardiomyopathy (HCM) and it was associated with a worse prognosis. Nevertheless in most HCM patients, despite normal pulmonary pressures at rest, congestive symptoms are elicited by exercise. In the present study, combining cardiopulmonary exercise test (CPET) with echocardiography, we aimed to evaluate the presence of exercise-induced pulmonary hypertension (EiPAH) its role in functional limitation and its prognostic significance in a cohort of patients with obstructive and non-obstructive HCM. Methods and results 182 HCM patients (35% females, mean age 47.5 ± 15.9) undergoing CPET. During CPET, LVOT velocities and trans-tricuspid gradient were measured. Thirty-seven patients (20%) developed sPAP > 40 mmHg at peak exercise (EiPAH). EiPAH was associated with an lower exercise performance, larger left atrial volumes, higher left ventricular gradient and higher VE/VCO2 slope .At multivariable model baseline sPAP (P Conclusions EiPAH was present in about one fifth of HCM patients without evidence of elevated pulmonary pressures at rest, and was associated with adverse clinical outcome. Diagnosing EiPAH by exercise echo/CPET may help physicians to detect early stage of PAH requiring a closer clinical monitoring and individualized treatment strategies.

Aims Incidence of stroke in patients with an advanced stage hypertrophic cardiomyopathy (HCM) is associated with adverse outcome, impaired quality of life and loss of productivity. Still today, however, the real burden of stroke in both patients with and without atrial fibrillation (AF) is unresolved. To assess the prevalence and incidence of AF and stroke in patients with an advanced stage HCM implanted with cardiac implantable electronic devices (CIEDs) at our institution, a long-standing high flow referral centre for cardiomyopathies. Methods and results Clinical and instrumental data of HCM patients implanted with CIEDs [either pacemakers (PM) or implantable cardioverter defibrillator (ICD)] from 1998 to 2019 were retrospectively reviewed. Inclusion criteria were site-designated diagnosis of HCM, age at diagnosis >18 years, Follow-up >1 year. HCM phenocopies (e.g. Fabry disease) were carefully excluded. Patients were divided into three categories according to presence of AF (‘AF prior to CIED implantation’ vs. ‘AF after CIED implantation’ vs. ‘sinus rhythm’). Outcome was measured against incidence of thromboembolic events [stroke or transient ischaemic attack (TIA)] at Follow-up. Patients were also stratified by left atrial diameter (LAD) in two groups ( 48mm). Of 1861 patients followed at our Unit, a total of 185 (9.9%) patients implanted with a CIED were included (57% men, mean age at implantation 54 ± 17 years). At baseline, AF was present in 72 (36%) patients. Mean CHA2DS2VASc was 1.7 + 1.3 with no differences among patients with or without AF. Patients with AF at baseline had a more pronounced LAD dilation (51 ± 7 vs. 44 ± 8, P 48 mm had the greatest risk of stroke (4.8%/year vs. 0.5%/year, P 48 vs. LAD Conclusions In a large cohort of consecutive high risk HCM patients referred to CIED implantation, the incidence of stroke was high, with 1-in-10 patients experiencing at least one event. Among patients in sinus rhythm, those with a marked left atrial dilatation were at highest risk of ischaemic stroke, suggesting the existence of an unmet need to stratify risk of stroke even in patients with no detected arrhythmias.

Aims Ventricular cardiomyocytes from hypertrophic cardiomyopathy (HCM) patient hearts show prolonged action potential duration (APD), impaired intracellular Ca2+ homeostasis and abnormal electrical response to beta -adrenergic stimulation. We sought to determine whether this behaviour is associated with abnormal changes of repolarization during exercise and worsening of diastolic function, ultimately explaining the intolerance to exercise experienced by some patients without obstruction. Methods and results Non-obstructive HCM patients (178) and control subjects (81) underwent standard exercise testing, including exercise echocardiography. Ventricular myocytes were isolated from myocardial samples of 23 HCM and eight non-failing non-hypertrophic surgical patients. The APD shortening in response to high frequencies was maintained in HCM myocytes, while β-adrenergic stimulation unexpectedly prolonged APDs, ultimately leading to a lesser shortening of APDs in response to exercise. In HCM vs. control subjects, we observed a lesser shortening of QT interval at peak exercise (QTc: +27 ± 52 ms in HCM, −4 ± 50 ms in controls, P 30 ms), the excessive shortening of the electrical diastolic period was linked with a limited increase of heart-rate and deterioration of diastolic function at peak effort. Conclusions Abnormal balance of Ca2+- and K+-currents in HCM cardiomyocytes determines insufficient APD and Ca2+-transient shortening with exercise. In HCM patients, exercise-induced QTc prolongation was associated with impaired diastolic reserve, contributing to the reduced exercise tolerance. Our results support the idea that severe electrical cardiomyocyte abnormalities underlie exercise intolerance in a subgroup of HCM patients without obstruction.

Heart failure with preserved ejection fraction (HFpEF) remains a poorly characterized syndrome with many unknown aspects related to different patient profiles, various associated risk factors and a wide range of aetiologies. It comprises several pathophysiological pathways, such as endothelial dysfunction, myocardial fibrosis, extracellular matrix deposition and intense inflammatory system activation. Until now, HFpEF has only been described with regard to clinical features and its most commonly associated risk factors, disregarding all biological mechanisms responsible for cardiovascular deteriorations. Recently, innovations in laboratory and metabolomic findings have shown that HFpEF appears to be strictly related to specific cells and molecular mechanisms’ dysregulation. Indeed, some biomarkers are efficient in early identification of these processes, adding new insights into diagnosis and risk stratification. Moreover, recent advances in intermediate metabolites provide relevant information on intrinsic cellular and energetic substrate alterations. Therefore, a systematic combination of clinical imaging and laboratory findings may lead to a ‘precision medicine’ approach providing prognostic and therapeutic advantages. The current review reports traditional and emerging biomarkers in HFpEF and it purposes a new diagnostic approach based on integrative information achieved from risk factor burden, hemodynamic dysfunction and biomarkers’ signature partnership.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare inherited disease caused by NOTCH3 gene mutations. Although the main clinical features reflect brain injury, CADASIL is a systemic microangiopathy, and cardiac involvement has been observed but not systematically assessed. We aimed to study the prevalence and severity of coronary microvascular dysfunction (CMD) in CADASIL patients.Seventeen patients with genetically confirmed CADASIL, aged60 years (mean age 40 ± 9 years), with ≤1 cardiovascular risk factor underwent neurological and neuropsychological evaluation, 3T brain magnetic resonance imaging (MRI), 12-lead electrocardiography (ECG), standard echocardiography, and measurement of myocardial blood flow at rest (resting MBF) and of maximal myocardial blood flow following Regadenoson infusion (Reg-MBF) byTwelve patients (71%) presented migraine, none (53%) had psychiatric disturbances, and one (6%) had a previous stroke. None had cognitive impairment or ECG or echocardiography abnormalities. Both Reg-MBF and CFR were blunted in CADASIL patients compared with controls (Reg-MBF 2.46 ± 0.54 vs. 3.09 ± 0.44 ml/g/min, respectively; p 0.01; CFR 2.74 ± 0.36 vs. 3.28 ± 0.66, respectively, p 0.01). No correlations were found between Reg-MBF values and neuropsychological performance or cerebral lesion burden on MRI.CADASIL patients exhibit blunted CFR due to CMD, which can be severe and is independent of the severity of brain lesion load and cognitive performances. CADASIL is a systemic microcirculation disease, and active surveillance of cardiac symptoms should be considered in these patients.

Introduction Atrial fibrillation (AF) is highly prevalent in patients with hypertrophic cardiomyopathy (HCM) and is associated with adverse outcome, impaired quality of life, loss of productivity, and the risk for embolic stroke. However, still today, the real burden of AF is unresolved due to the unknown frequency of silent asymptomatic episodes. Purpose To assess the prevalence of device-detected AF and stroke in patients with HCM implanted with cardiac implantable electronic devices (CIEDs) at our institution, a long-standing high flow referral center for cardiomyopathies. Methods Clinical and instrumental data of HCM patients implanted with CIEDs (either pacemakers [PM] or implantable cardioverter defibrillator [ICD]) from 1998 to 2019 were retrospectively reviewed. Inclusion criteria were site-designated diagnosis of HCM, age at diagnosis >18 years, >1 follow up visit, follow up >1 year. HCM phenocopies (e.g. Fabry disease) were carefully excluded. Patients were divided into three categories according to presence of AF (“AF prior to CIED implantation” vs “AF after CIED implantation” vs “no arrhythmia detected”). Outcome was measured against prevalence of thromboembolic events (stroke or transient ischemic attack [TIA]) at follow up. All-cause and cardiovascular (CV) mortality were also assessed. Results A total of 255 patients received a CIED (57% men, mean age at implantation 54±17 years). Men were younger at implantation (52±17 vs 56±18 years, p=0.022). At baseline, AF was present in 90 (35.3%) patients. During 5.0±4.1 years, de novo AF was detected in 30 (11.8%) individuals, resulting in an annual incidence rate of 6.1%/year. Overall, 135 (52.9%) of patients remained is sinus rhythm. Stroke/TIAs were reported in 30 (11.8%) patients: 16 (53.3%) occurred in patients with prior history of AF, 3 (10%) in patients with de novo AF (with men being at higher risk, OR 3.73, 95% CI 1.88–6.09, p=0.041), and 11 (36.7%) in patients with no history of arrhythmias. Long term, 45 (17.6%) patients died (CV mortality N=38, 14.9%). At multivariable analysis, history of stroke was directly related to all-cause mortality irrespective of AF in men (OR 4.15, 95% CI 1.35–12.77, p=0.018) but not in women (OR 0.891, 95% CI 0.17–4.64, p=0.801). Conclusions In a large cohort of consecutive high risk HCM patients referred to CIED implantation, the incidence of de-novo AF was high. Thromboembolic events were associated to worse outcome only in men, likely due to competing heart failure related causes in women. Strategies promoting early identification of AF and anticoagulation may play an important role in management and prevention of disease-related complications. Prevalence of AF and Stroke Funding Acknowledgement Type of funding source: None

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL; OMIM 125310) is a rare inherited disease, caused by NOTCH3 gene mutations. Main clinical manifestations of CADASIL include recurrent subcortical ischemic events, migraine, cognitive impairment and psychiatric disturbances. CADASIL is a systemic microangiopathy and cardiac involvement has been observed in a series of Dutch patients, presenting higher frequency of myocardial infarction compared to non-mutated relatives and general population. In particular, electron microscopic examination of myocardial tissue of a study participant demonstrated CADASIL characteristics. We sought to investigate the relationship between CADASIL and microvascular dysfunction (MVD). Seventeen patients with genetically-confirmed CADASIL, aged Mean age was 40±9 years (range 28–57 years); 6 patients (35%) were male. One was a current smoker and 3 ex-smokers; 1 patient was on aspirin, 1 on acetazolamide and 2 on escitalopram, none was taking statins. 12 patients (71%) presented with migraine, 9 (53%) had psychiatric disturbances and 1 (6%) had a previous stroke. Brain MRI showed mild-moderate and severe leukoencephalopathy in 11 (65%) and 5 (29%) patients respectively, lacunes were present in 14 patients and microbleeds in 1; one patient had normal findings. Both Reg-MBF and CFR were blunted in CADASIL patients compared with controls (Reg-MBF 2.46±0.54 versus 3.09±0.44 ml/gr/min respectively, p These data represent the first documentation of coronary microvascular involvement in a group of young and mildly symptomatic CADASIL patients, confirming the systemic nature of the disease. This proof of concept study expands our understanding of genetically-driven CMD. Funding Acknowledgement Type of funding source: None

Introduction Eosinophilic granulomatosis with polyangiitis (EGPA) is an extremely rare necrotizing vasculitis affecting small- and medium-sized vessels. EGPA may affect the heart leading to myocardial inflammation and necrosis. Although, only a few cardiological based studies have been conducted. Purpose This study aimed to investigate the prevalence and clinical impact of cardiac-specific involvement (CSI+) and to give an update on EGPA cardiological manifestations. Methods This is a single-centre study. Cardiological evaluation included ECG, blood test, echocardiography, global longitudinal strain (GLS), cardiac magnetic resonance (CMR). Results We prospectively enrolled 52 consecutive EGPA patients, between October 2018 and October 2019, mean age 59±3 years, 30 (57%) female. We identified 13 (25%) CSI+ patients: 6 myocarditis, 2 pericarditis, 1 coronaritis, 1 Prinzmetal angina, 2 LV apical thrombosis, 1 unexplained wall motions abnormalities (WMA) in the absence of coronary artery disease. Twelve-leads ECG revealed abnormalities in 11 (85%) CSI+ vs 9 (23%) CSI−, p=0.0001; ECG abnormalities identified CSI+ with 85% sensitivity, 77% specificity, 94% negative predictive value. Median troponin level in CSI+ 9 ng/L (IQR 6–11) vs CSI− 11 ng/L (IQR 6–25), p=0.2548; NT-pro-BNP value in CSI+ 210 pg/L (IQR 175–484) vs CSI− 159 ng/L (IQR 66–299), p=0.0576. Echocardiographic left ventricular end diastolic volume in CSI+ 62±4 ml/m2 vs CSI− 52±1 ml/m2, p=0.0116; LV ejection fraction in CSI+ 57%±2 vs CSI− 66%±1, p=0.0002. In CSI+ patients GLS was −15±1 vs CSI− GLS −21±0.4, p Twelve patients underwent CMR, it showed non ischaemic late gadolinium enhancement in 7 patients; in 5 patients we identified akinetic or dyskinetic segments without associated LGE. Two patients showed LV apical thrombus. Conclusions EGPA showed a high prevalence of CSI. We repeatedly found a tropism for apical involvement in WMA that often manifested themselves as apical aneurysm. These may be a new clinical feature, previously not described, in such a rare condition. Cardiac involvement EGPA Funding Acknowledgement Type of funding source: None

Background Left ventricular non-compaction (LVNC) is a condition characterised by trabeculations in the myocardial wall and is the subject of considerable conjecture as to whether it represents a distinct pathology or a secondary phenotype associated with other cardiac diseases, particularly cardiomyopathies. Purpose To investigate the genetic architecture of LVNC by identifying genes and variant classes robustly associated with disease and comparing these to other genetically characterised cardiomyopathies. Methods We performed rare variant association analysis using six different LVNC cohorts comprising 840 cases together with 125,748 gnomAD population controls and compared results to similar analyses with dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) cases. Results We observed substantial overlap in genes and variant classes enriched in LVNC and DCM/HCM, indicating that in many cases LVNC belongs to a spectrum of more established cardiomyopathies, with non-compaction representing a phenotypic variation in patients with DCM- or HCM-causing variants. In contrast, five variant classes were uniquely enriched in LVNC cases, of which truncating variants in MYH7, ACTN2 and PRDM16 may represent a distinct LVNC aetiology. MYH7 truncating variants are generally considered as non-pathogenic but were detected in 2% of LVNC cases compared to 0.1% of controls, including a cluster of variants around a single splice region. Additionally, structural variants (exon deletions) in RYR2 and missense variants in the transmembrane region of HCN4 were enriched in LVNC cases, confirming prior reports regarding the association of these variant classes with combined LVNC and arrhythmia phenotypes. Conclusions We demonstrated that genetic association analysis can clarify the relationship between LVNC and established cardiomyopathies, highlighted substantial overlap with DCM/HCM but also identified variant classes associated with distinct LVNC and with joint LVNC/arrhythmia phenotypes. These results underline the complex genetic landscape of LVNC and inform how genetic testing in LVNC cases should be pursued and interpreted. Cardiomyopathy rare variant frequencies Funding Acknowledgement Type of funding source: None

Patients with heart failure (HF) and associated chronic kidney disease (CKD) are a population less represented in clinical trials; additionally, subjects with more severe estimated glomerular filtration rate reduction are often excluded from large studies. In this setting, most of the data come from post hoc analyses and retrospective studies. Accordingly, in patients with advanced CKD, there are no specific studies evaluating the long-term effects of the traditional drugs commonly administered in HF. Current concerns may affect the practical approach to the traditional treatment, and in this setting, physicians are often reluctant to administer and titrate some agents acting on the renin angiotensin aldosterone system and the sympathetic activity. Therefore, the extensive application in different HF subtypes with wide associated conditions and different renal dysfunction etiologies remains a subject of debate. The role of novel drugs, such as angiotensin receptor blocker neprilysin inhibitors and sodium glucose linked transporters 2 inhibitors seems to offer a new perspective in patients with CKD. Due to its protective vascular and hormonal actions, the use of these agents may be safely extended to patients with renal dysfunction in the long term. In this review, we discussed the largest trials reporting data on subjects with HF and associated CKD, while suggesting a practical stepwise algorithm to avoid renal and cardiac complications.

The exact relationship existing among congestion status, brain natriuretic peptide (BNP) changes and acute kidney injury (AKI) has not been elucidated in patients with acute heart failure (AHF). The aims of this study are: to investigate the relation and prognostic role of BNP, AKI and clinical congestion after discharge; to define the exact BNP cut off value or a BNP in-hospital reduction to identify patients with higher risk during vulnerable post-discharge phase. We consecutively enrolled 157 patients with a diagnosis of AHF. BNP and creatinine were measured in all patients, and degree of failure was assessed. AKI was defined as a creatinine increase ≥0.3 mg/dL or eGFR reduction ≥20% during hospitalization. All patients were followed for 1 and 3 months. Of 146 included patients, 110 patients (75%) displayed effective decongestion, 116 (79%) showed a BNP decrease ≥30%, and 28 (19%) developed in-hospital AKI. BNP in-hospital decrease ≥30% was found more often in patients who showed good decongestion in comparison to patients in persistent failure (63 vs 22%; p

BackgroundLeft ventricular non-compaction (LVNC) is a condition characterised by trabeculations in the myocardial wall and is the subject of considerable conjecture as to whether it represents a distinct pathology or a secondary phenotype associated with other cardiac diseases, particularly cardiomyopathies. We sought to investigate the genetic architecture of LVNC by identifying genes and variant classes robustly associated with disease and comparing these to other genetically characterised cardiomyopathies.MethodsWe performed rare variant association analysis using six different LVNC cohorts comprising 840 cases together with 125,748 gnomAD population controls and compared results to similar analyses with dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) cases.ResultsWe observed substantial overlap in genes and variant classes enriched in LVNC and DCM/HCM, indicating that in many cases LVNC belongs to a spectrum of more established cardiomyopathies, with non-compaction representing a phenotypic variation in patients with DCM- or HCM-causing variants. In contrast, five variant classes were uniquely enriched in LVNC cases, of which truncating variants inMYH7, ACTN2andPRDM16may represent a distinct LVNC aetiology.MYH7truncating variants are generally considered as non-pathogenic but were detected in 2% of LVNC cases compared to 0.1% of controls, including a cluster of variants around a single splice region. Individuals withMYH7truncating variants identified in the UK Biobank and cohorts of healthy volunteers also displayed significantly greater non-compaction compared to matched controls, with 50% meeting the diagnostic criteria for LVNC. Additionally, structural variants (exon deletions) inRYR2and missense variants in the transmembrane region ofHCN4were enriched in LVNC cases, confirming prior reports regarding the association of these variant classes with combined LVNC and arrhythmia phenotypes.ConclusionsWe demonstrated that genetic association analysis can clarify the relationship between LVNC and established cardiomyopathies, highlighted substantial overlap with DCM/HCM but also identified variant classes associated with distinct LVNC and with joint LVNC/arrhythmia phenotypes. These results underline the complex genetic landscape of LVNC and inform how genetic testing in LVNC cases should be pursued and interpreted.

Introduction The presence of sarcomere mutations is a powerful predictor of heart failure-related outcomes in Hypertrophic Cardiomyopathy (HCM). However, whether the prevalence of left ventricular (LV) dysfunction differs in patients with mutations in the two most prevalent HCM-associated genes (i.e. MYBPC3 and MYH7) is unclear. Purpose To ascertain lifetime trends in prevalence of LV dysfunction in HCM associated with pathogenic or likely-pathogenic MYBPC3 versus MYH7 mutations. Methods Clinical and instrumental records of 402 HCM patients with MYBPC3 (N=251) or MYH7 (N=151) mutations were retrospectively reviewed. Presence of systolic dysfunction (ejection fraction [EF] Results Patients were diagnosed at a mean age of 39±17 years and 63% were men. At first evaluation MYBPC3-HCM patients were less frequently obstructive (15% vs 26% in MYH7; p=0.005) and had lower LVEF (61±11% vs 64±9%; p=0.01). Prevalence of diastolic dysfunction increased with age and was lowest in MYBPC3 patients No significant differences were observed in terms of NYHA class change, atrial fibrillation, stroke, heart failure, appropriate ICD intervention or cardiovascular death. However, prevalence of NSVT was higher for MYBPC3 (39% vs 14% in MYH7, p In vitro cross-sectional evaluation of myocardial samples taken during septal myectomy at different ages showed a decline in contraction-relaxation properties after age 40 in MYPBC3 carriers, but preserved function in MYH7 patients (Figure). Kinetic of myosin cross-bridges Conclusions In HCM patients, mutations in the MYBPC3 gene and early diagnosis are associated with slowly progressing systolic impairment leading to overt dysfunction in 15% compared to 5% in MYH7-HCM. However, outcome was similar in the two subsets. These differences in lifetime myocardial performance between the two most common HCM-associated genes suggest diverse pathways of disease progression, potentially amenable to requiring different molecular approaches.

Left bundle branch block (LBBB) is the most reliable electrocardiographic predictor of responsiveness to cardiac resynchronization therapy (CRT). However, not all patients with LBBB will respond to CRT. Our aim was to investigate the interaction between QRS duration, LBBB-type morphology, and the responsiveness to CRT. We retrospectively analyzed electrocardiograms of 243 patients who underwent CRT implantation according to current clinical indications. A 6-month reduction of left ventricular end-systolic volume >15% was used to identify CRT responders. The clinical end point consisted of death, hospitalization for heart failure and sustained rapid ventricular tachyarrhythmias. An LBBB morphology was present in 169 patients (70%) and 101 of these (60%) were responders to CRT. Analyzing the interaction between QRS duration and CRT responsiveness in patients with LBBB, a "U shaped" distribution resulted, with nonresponders clustered between 120 and 130 ms and above 180 ms. The receiver operating characteristic curve analysis identified 178 ms as the optimal cut-off value of QRS to predict a nonresponsiveness to CRT (area under the curve = 0.67 [95% confidence interval 0.57 to 0.76]). At multivariate analysis, only an ischemic cause and a QRS ≥178 ms were independent predictors of nonresponsiveness to CRT (area under the curve = 0.75). Patients with LBBB with QRS ≥178 ms had greater likelihood of adverse clinical events during a mean follow-up of 32 months (p = 0.049). In conclusion, in patients with LBBB undergoing CRT, a marked QRS widening (i.e., ≥178 ms) is related to worse echocardiographic responsiveness and lower event free survival rate compared with patients with an intermediate QRS widening. Left bundle branch block (LBBB) is the most reliable electrocardiographic predictor of responsiveness to cardiac resynchronization therapy (CRT). However, not all patients with LBBB will respond to CRT. Our aim was to investigate the interaction between QRS duration, LBBB-type morphology, and the responsiveness to CRT. We retrospectively analyzed electrocardiograms of 243 patients who underwent CRT implantation according to current clinical indications. A 6-month reduction of left ventricular end-systolic volume >15% was used to identify CRT responders. The clinical end point consisted of death, hospitalization for heart failure and sustained rapid ventricular tachyarrhythmias. An LBBB morphology was present in 169 patients (70%) and 101 of these (60%) were responders to CRT. Analyzing the interaction between QRS duration and CRT responsiveness in patients with LBBB, a "U shaped" distribution resulted, with nonresponders clustered between 120 and 130 ms and above 180 ms. The receiver operating characteristic curve analysis identified 178 ms as the optimal cut-off value of QRS to predict a nonresponsiveness to CRT (area under the curve = 0.67 [95% confidence interval 0.57 to 0.76]). At multivariate analysis, only an ischemic cause and a QRS ≥178 ms were independent predictors of nonresponsiveness to CRT (area under the curve = 0.75). Patients with LBBB with QRS ≥178 ms had greater likelihood of adverse clinical events during a mean follow-up of 32 months (p = 0.049). In conclusion, in patients with LBBB undergoing CRT, a marked QRS widening (i.e., ≥178 ms) is related to worse echocardiographic responsiveness and lower event free survival rate compared with patients with an intermediate QRS widening.

Many trials demonstrated the beneficial effects on hospitalizations and mortality of cardiac resynchronization therapy (CRT). The purpose of this study was to evaluate CRT effects on functional performance and cognition, two determinants of disability, frailty development and survival.All consecutive patients receiving a CRT device were evaluated at baseline and at the 6-month follow-up. Functional profile was assessed with the Short Physical Performance Battery (SPPB), a measure exploring balance, gait, strength and endurance, highly predictive of incident disability and mortality. The Mini-Mental State Examination (MMSE) was used to study the cognitive profile.We enrolled 54 patients; two of them died during the follow-up, two refused to continue the study. Age was 67±10years (men: 80%, LVEF: 28±5%); medical therapy was optimized (ACE-I/ARB: 84%, beta-blockers: 80%). After 6months, CRT was associated with the improvement of LVEF (35±8 vs. 28±5%, p0.001) and NYHA Class (1.8±0.6 vs. 2.6±0.5, p0.001), and with the reduction of left ventricular end-systolic diameter (50±9 vs. 57±9mm, p0.001). SPPB improved in its total score (10.3±2.0 vs. 9.1±2.7, p0.001) and in the scores exploring gait speed and strength and endurance. These changes were associated with a better cognitive profile (MMSE score: 27.0±3.5 vs. 25.9±4.8, p=0.009). Advanced age was an independent predictor of improved functional performance and cognition.CRT is associated with higher functional and cognitive profile after only 6months of therapy. These findings let us hypothesize a powerful effect of treatment to slow disability and frailty development in heart failure.

BackgroundAlmost half of patients with acute heart failure have preserved ejection fraction (HFpEF). HFpEF is a diagnostic challenge using traditional investigation tools; Galectin-3 (Gal-3) is an emerging biomarker useful in individuals at risk for HF. The aim of our study is to analyse the relation and prognostic value of Gal-3, BNP and renal dysfunction in patients with HFpEF compared to patients with reduced ejection fraction (HFrEF).MethodsWe enrolled 98 patients with acute heart failure (AHF) and measured Gal-3, BNP, and estimated glomerular filtration rate (eGFR) within 12 h of hospital admission. On the basis of echocardiographic findings we divided our sample into two groups: patients with HFrHF (ejection fraction 50%). Patients were followed up at 6 months.ResultsNo differences in Gal-3 levels were found in the two subgroups (HFrEF: 19.5 ± 5.1 ng/mL; HFpEF: 20.5 ± 8.7, p = 0.56). Gal-3 was inversely related to renal dysfunction (LogGal-3 vs eGFR: r = − 0.30, p = 0.01) but did not correlate with LogBNP levels (r = 0.07, p = 0.55). Gal-3 was associated with more advanced diastolic dysfunction in HFpEF (p = 0.009). In addition LogGal-3 was related to diastolic LV stiffness (all patients: r = 0.45, p 1.30 was related to poor outcome independently from renal dysfunction and other risk factors only in HFpEF (univariate HR 23.98 [3.03–89.45]; p ConclusionsGal-3 is not able to distinguish between HFrEF and HFpEF patients. However it is related to diastolic dysfunction severity and LV stiffness in HFpEF. Gal-3 demonstrates a prognostic role independently from renal dysfunction in subjects with HFpEF.

Heart Failure (HF) is characterized by an elevated readmission rate, with almost 50% of events occurring after the first episode over the first 6 months of the post-discharge period. In this context, the vulnerable phase represents the period when patients elapse from a sub-acute to a more stabilized chronic phase. The lack of an accurate approach for each HF subtype is probably the main cause of the inconclusive data in reducing the trend of recurrent hospitalizations. Most care programs are based on the main diagnosis and the HF stages, but a model focused on the specific HF etiology is lacking. The HF clinic route based on the HF etiology and the underlying diseases responsible for HF could become an interesting approach, compared with the traditional programs, mainly based on non-specific HF subtypes and New York Heart Association class, rather than on detailed etiologic and epidemiological data. This type of care may reduce the 30-day readmission rates for HF, increase the use of evidence-based therapies, prevent the exacerbation of each comorbidity, improve patient compliance, and decrease the use of resources. For all these reasons, we propose a dedicated outpatient HF program with a daily practice scenario that could improve the early identification of symptom progression and the quality-of-life evaluation, facilitate the access to diagnostic and laboratory tools and improve the utilization of financial resources, together with optimal medical titration and management.

Myocardial infarction (MI) results in myocardial scarring which can have an impact on left ventricular (LV) stiffness and contractile function, ultimately leading to reduced LV systolic function and LV remodelling, However some concerns about the relation between scar extension and segmental wall motion contractility is not enough clear. Thus, the association between myocardial scar, LV regional and global function and LV remodeling should be investigated. We studied the relationship between scar extension, wall motion score index (WMSI), LV dimensions and systolic function in a group of patients with previous MI by cardiac magnetic resonance (CMR). 133 patients with previous (>6 month) MI were retrospectively enrolled in the study. Indexed end-systolic volume (ESVi), indexed end-diastolic volume (EDVi), LV ejection fraction (EF), stroke volume (SV), LV mass were measured using CMR. WMSI and sum scar score (SSS) were also measured following AHA\ACC criteria giving an arbitrary cut-off to distinguish larger from restricted late gadolinium enhancement (LGE) area. A total of 2261 segments were studied: regional wall motion abnormalities were present in 1032 segments (45%) and 724 (32%) showed presence of MI (LGE). WMSI correlated significantly with EF (r = -0.87, p < 0.0001) in all patients and in both patients with EF ≥ 40% (r = -0.77, p < 0.0001) and EF < 40% (r = -0.68, p < 0.0001). WMSI also correlated significantly with SSS (r = 0.57, p < 0.0001). The correlation between WMSI and SSS was more significant in patients with transmural MI (WMSI 2.1 ± 0.5 and SSS 17 ± 8; r = 0.55, p < 0.0001) than with non transmural MI (WMSI 1.6 ± 0.7 and SSS 6 ± 4; r = 0.34 and p = 0.02). A significant correlation was also found between EF and SSS (r = -0.55 and p < 0.0001) and between SSS and LV indexed volumes (EDVi; r = 0.44, p < 0.0001 and ESVi; r = 0.51, p < 0.0001). Infarct transmurality and extension as expressed as SSS assessed with cardiac MRI has an impact on global and regional systolic function. A multi-parametric score measuring WMSI scar transmurality and extension, could better identify an increased cardiac remodeling after coronary event.

AIM Functional analysis and measurement of left atrium are an integral part of cardiac evaluation, and they represent a key element during non-invasive analysis of diastolic function in patients with hypertension (HT) and/or heart failure with preserved ejection fraction (HFpEF). However, diastolic dysfunction remains quite elusive regarding classification, and atrial size and function are two key factors for left ventricular (LV) filling evaluation. Chronic left atrial (LA) remodelling is the final step of chronic intra-cavitary pressure overload, and it accompanies increased neurohormonal, proarrhythmic and prothrombotic activities. In this systematic review, we aim to purpose a multi-modality approach for LA geometry and function analysis, which integrates diastolic flow with LA characteristics and remodelling through application of both traditional and new diagnostic tools. METHODS The most important studies published in the literature on LA size, function and diastolic dysfunction in patients with HFpEF, HT and/or atrial fibrillation (AF) are considered and discussed. RESULTS In HFpEF and HT, pulsed and tissue Doppler assessments are useful tools to estimate LV filling pressure, atrio-ventricular coupling and LV relaxation but they need to be enriched with LA evaluation in terms of morphology and function. An integrated evaluation should be also applied to patients with a high arrhythmic risk, in whom eccentric LA remodelling and higher LA stiffness are associated with a greater AF risk. CONCLUSION Evaluation of LA size, volume, function and structure are mandatory in the management of patients with HT, HFpEF and AF. A multi-modality approach could provide additional information, identifying subjects with more severe LA remodelling. Left atrium assessment deserves an accurate study inside the cardiac imaging approach and optimised measurement with established cut-offs need to be better recognised through multicenter studies.

Background: \ud Lung ultrasound (LUS) can be used to assess pulmonary congestion by imaging B-lines (‘comets’) for patients with acute heart failure (AHF).\ud \ud Objectives: \ud Investigate relationship of B-lines, plasma concentrations of B-type natriuretic peptide (BNP), and echocardiographic left ventricular (LV) function measured at admission and discharge and their relationship to prognosis for AHF with preserved (HFpEF) or reduced (HFrEF) LV ejection fraction.\ud \ud Methods: \ud Patients with AHF had the above tests done at admission and discharge. The primary outcome was re-hospitalization for heart failure or death at 6 months.\ud \ud Results: \ud Of 162 patients enrolled, 95 had HFrEF and 67 had HFpEF, median age was 80 [77–85] years, and 85 (52%) were women. The number of B-lines at admission (median 31 [27–36]) correlated with respiratory rate (r = 0.75; p

Left ventricular (LV) dyssynchrony (LVdys) is a necessary condition for successful cardiac resynchronization therapy (CRT). Despite left bundle branch block (LBBB) representing a reliable surrogate of LVdys, not all LBBB patients will respond to CRT. Our aim was to investigate the relation between QRS duration and LVdys in patients with LBBB who underwent CRT. We retrospectively studied 165 patients with LBBB who underwent CRT implantation according to the current guidelines. A 6-month reduction of LV end-systolic volume ≥15% identified responders to CRT. Baseline LVdys was defined as the delay between peak systolic velocities of the interventricular septum and lateral wall assessed by color-coded tissue Doppler imaging. Baseline characteristics of responders (61%) and nonresponders (39%) were comparable except for larger QRS complex (172 ± 24 vs 160 ± 16 ms, p 3 remained an independent predictor at multivariate analysis. In patients with nonischemic origin of cardiomyopathy, the linear regression analysis documented a significant inverse relation between QRS duration and LVdys, as dyssynchrony progressively decreased as QRS widening increased (p = 0.006). This was not evident in patients with ischemic origin. In conclusion, in LBBB patients with nonischemic origin and marked QRS widening, the absence of LVdys may account for a lower response to CRT compared with patients with intermediate QRS widening.

Serum uric acid (UA) is associated with death and hospitalization in chronic heart failure (HF). However, UA in acute HF has not been well studied with respect to its relation to renal dysfunction and vascular congestion. We measured admission serum UA along with baseline variables in 281 patients with acute HF screened from the Loop Diuretics Administration and Acute Heart Failure (Diur-HF) trial. Hyperuricemia was defined as serum UA7 mg/dl in men and6 mg/dl in women. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate60 ml/min/1.73 m(2) before hospital admission. Death or HF hospitalization at 6 months was the primary outcome. The mean UA concentration was 6.4 ± 2.5 mg/dl, and 121 patients (43.1%) were classified as hyperuricemic. UA values were significantly increased in patients with CKD compared to patients without CKD (6.8 ± 2.7 vs 6.1 ± 2.1 mg/dl; p = 0.02); however, UA was not associated with the development of acute kidney injury. Patients with hyperuricemia had greater degrees of pulmonary and systemic congestion than normouricemic patients (congestion score 3.5 vs 2.1, p0.01). Hyperuricemia was associated with higher risk of death or HF rehospitalization (univariate hazard ratio 1.46 [1.02 to 2.10]; p = 0.04, multivariate hazard ratio 1.69 [1.16 to 2.45]; p = 0.005). In conclusion, hospitalized patients with acute HF, elevated UA levels were associated with both CKD and pulmonary congestion. After controlling for potential confounders, hyperuricemia was associated with rehospitalization and death at 6 months.