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IMPORTANCE: Although the results of A Study to Evaluate the Corvia Medical Inc IASD System II to Reduce Elevated Left Atrial Pressure in Patients with Heart Failure (REDUCE LAP-HF II) trial were neutral overall, atrial shunt therapy demonstrated potential efficacy in responders (no latent pulmonary vascular disease and no cardiac rhythm management device). Post hoc analyses were conducted to evaluate the effect of shunt vs sham stratified by responder status. OBJECTIVE: To evaluate the effect of atrial shunt vs sham control on cardiac structure/function in the overall study and stratified by responder status. DESIGN, SETTING, AND PARTICIPANTS: This was a sham-controlled randomized clinical trial of an atrial shunt device in heart failure with preserved ejection fraction (HFpEF)/HF with mildly reduced EF (HFmrEF). Trial participants with evaluable echocardiography scans were recruited from 89 international medical centers. Data were analyzed from April 2023 to January 2024. INTERVENTIONS: Atrial shunt device or sham control. MAIN OUTCOME MEASURES: Changes in echocardiographic measures from baseline to 1, 6, 12, and 24 months after index procedure. RESULTS: The modified intention-to-treat analysis of the REDUCE LAP-HF II trial included 621 randomized patients (median [IQR] age, 72.0 [66.0-77.0] years; 382 female [61.5%]; shunt arm, 309 [49.8%]; sham control arm, 312 [50.2%]). Through 24 months, 212 of 217 patients (98%) in the shunt arm with evaluable echocardiograms had patent shunts. In the overall trial population, the shunt reduced left ventricular (LV) end-diastolic volume (mean difference, −5.65 mL; P <.001), left atrial (LA) minimal volume (mean difference, −2.8 mL; P =.01), and improved LV systolic tissue Doppler velocity (mean difference, 0.69 cm/s; P <.001) and LA emptying fraction (mean difference, 1.88 percentage units; P =.02) compared with sham. Shunt treatment also increased right ventricular (RV; mean difference, 9.58 mL; P <.001) and right atrial (RA; mean difference, 9.71 mL; P <.001) volumes but had no effect on RV systolic function, pulmonary artery pressure, or RA pressure compared with sham. In the shunt arm, responders had smaller increases in RV end-diastolic volume (mean difference, 5.71 mL vs 15.18 mL; interaction P =.01), RV end-systolic volume (mean difference, 1.58 mL vs 7.89 mL; interaction P =.002), and RV/LV ratio (mean difference, 0.07 vs 0.20; interaction P <.001) and larger increases in transmitral A wave velocity (mean difference, 5.08 cm/s vs −1.97 cm/s; interaction P =.02) compared with nonresponders randomized to the shunt, suggesting greater ability to accommodate shunted blood through the pulmonary circulation enabling LA unloading. CONCLUSIONS AND RELEVANCE: In this post hoc analysis of the REDUCE LAP-HF II trial, over 2 years of follow-up, atrial shunting led to reverse remodeling of left-sided chambers and increases in volume of right-sided chambers consistent with the shunt flow but no change in RV systolic function compared with sham. Changes in cardiac structure/function were more favorable in responders compared with nonresponders treated with the shunt, supporting the previously identified responder group hypothesis and mechanism, although further evaluation with longer follow-up is needed. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03088033

Patients with heart failure experience limitations in daily activity and poor quality-of-life. Prospective surveillance of health-related quality-of-life supplemented traditional death and hospitalization outcomes in the multinational, randomized, double-blinded CHART-1 clinical trial that assessed cardiopoiesis-guided cell therapy in ischemic heart failure patients with reduced left ventricular ejection fraction. The Minnesota Living with Heart Failure Questionnaire (MLHFQ), a Food and Drug Administration qualified instrument for evaluating therapeutic effectiveness, was applied through the 1-year follow-up. Cell treated (n= 109) and sham procedure (n= 140) cohorts reported improved MLHFQ scores comparable between the 2 study arms (mean treatment difference with baseline adjustment −3.2 points, P= .107). Superiority of cell treatment over sham in betterment of the MLHFQ score was demonstrated in patients with pre-existing advanced left ventricular enlargement (baseline-adjusted mean treatment difference −6.4 points, P= .009). In this highly responsive subpopulation, benefit on the MLHFQ score paralleled reduction in death and hospitalization post-cell therapy (adjusted Mann-Whitney odds 1.43, 95% CI, 1.01-2.01; P= .039). The potential of cell therapy in addressing the quality-of-life dimension of heart failure requires further evaluation for disease relief.Graphical AbstractBenefit afforded by regenerative biotherapy is typically assessed using physician-reported outcomes, such as functional recovery, hospitalization, and mortality. In the setting of a phase III clinical trial for heart failure, this study integrates the patients’ perception of disease burden on daily living documenting that stem cell therapy, delivered as an adjunct to standard-of-care, significantly improved health-related quality-of-life.

The assessment of myocardial work (MW) using noninvasive pressure-strain loop analysis is a novel echocardiographic method that provides a more precise assessment of cardiac performance by considering the left ventricular loading condition. By integrating various MW components such as index, efficiency, and constructive and wasted work, an extensive analysis of left ventricular mechanics and energetics can be achieved. This approach offers a more comprehensive assessment of global cardiac function and performance, surpassing conventional surrogate indices. In this review, we aim to summarize the existing knowledge on MW and its distinctive characteristics in various cardiac pathologies.

Atrial fibrillation (AF) is a common comorbidity in patients with heart failure with preserved ejection fraction (HFpEF) and in heart failure with mildly reduced ejection fraction (HFmrEF).

To assess aortic regurgitation (AR) prevalence, its hemodynamic effect, and long-term prognostic implications in patients admitted with de novo or worsened heart failure with preserved ejection fraction (HFpEF).

AbstractObjectiveAutonomic disorders are common in chronic illness, and their symptoms may restrict the daily functioning of patients. However, in chronic heart failure, extensive knowledge about autonomic symptoms is still lacking. This study aims to explore self-perceived autonomic symptoms, associated factors, and their relationship with health-related quality of life in chronic heart failure.MethodsOne hundred and twenty-four patients with documented chronic heart failure (men and women; 50–86 years) and 124 sex and age-matched controls participated in this study. The participants filled validated questionnaires about autonomic symptom profile (COMPASS 31), fatigue (CIS, Checklist for individual strength), anxiety and depression (HADS, Hospital Anxiety and Depression), and health-related quality of life (SF36). Non-parametric statistics were performed to analyse the data.ResultsTotal score for autonomic symptoms was higher in chronic heart failure compared to controls [Median: 14.9; IQR: 6.2–25.1 vs.7.3; 0–18; p < 0.001], especially for orthostatic hypotension [Median: 8; IQR: 0–16 vs.0; 0–12; p < 0.001], vasomotor [Median: 0; IQR: 0–0 vs.0; 0–0; p < 0.001] and secretomotor function [Median: 0; IQR: 0–4.2 vs.0; 0–2.1; p = 0.013]. High scores for autonomic symptoms were moderate correlated with higher scores of fatigue, anxiety and depression (0.343 ≤ rs ≥ 0.420; p < 0.001) and with decreased health-related quality of life (−0.454; p < 0.01).ConclusionAutonomic symptoms, especially for orthostatic intolerance, vasomotor and secretomotor subdomains, are prevalent and are associated with fatigue complaints and poor health-related quality of life in CHF.

ObjectiveDigital healthcare systems could provide insights into the global prevalence of heart failure (HF). We designed the CardioRenal and Metabolic disease (CaReMe) HF study to estimate the prevalence, key clinical adverse outcomes and costs of HF across 11 countries.MethodsIndividual level data from a contemporary cohort of 6 29 624 patients with diagnosed HF was obtained from digital healthcare systems in participating countries using a prespecified, common study plan, and summarised using a random effects meta-analysis. A broad definition of HF (any registered HF diagnosis) and a strict definition (history of hospitalisation for HF) were used. Event rates were reported per 100 patient years. Cumulative hospital care costs per patient were calculated for a period of up to 5 years.ResultsThe prevalence of HF was 2.01% (95% CI 1.65 to 2.36) and 1.05% (0.85 to 1.25) according to the broad and strict definitions, respectively. In patients with HF (broad definition), mean age was 75.2 years (95% CI 74.0 to 76.4), 48.8% (40.9–56.8%) had ischaemic heart disease and 34.5% (29.4–39.6%) had diabetes. In 51 442 patients with a recorded ejection fraction (EF), 39.1% (30.3–47.8%) had a reduced, 18.8% (13.5–24.0%) had a mildly reduced and 42.1% (31.5–52.8%) had a preserved left ventricular EF. In 1 69 518 patients with recorded estimated glomerular filtration rate, 49% had chronic kidney disease (CKD) stages III–V. Event rates were highest for cardiorenal disease (HF or CKD) and all cause mortality (19.3 (95% CI 11.3 to 27.1) and 13.1 (11.1 to 15.1), respectively), and lower for myocardial infarction, stroke and peripheral artery disease. Hospital care costs were highest for cardiorenal diseases.ConclusionsWe estimate that 1–2% of the contemporary adult population has HF. These individuals are at significant risk of adverse outcomes and associated costs, predominantly driven by hospitalisations for HF or CKD. There is considerable public health potential in understanding the contemporary burden of HF and the importance of optimising its management.

BackgroundHeart valve clinics (HVC) have been introduced to manage patients with valvular heart disease within a multidisciplinary team.ObjectiveTo determine the outcome benefit of HVC approach compared with standard of care (SOC) for patients with moderate and asymptomatic severe aortic stenosis (mAS and asAS).MethodsSingle-centre, observational registry of patients with mAS and asAS with at least one cardiac ambulatory consultation at our Cardiovascular Centre. Based on the outpatient strategy, patients were divided into HVC group, if receiving at least one visit at HVC, and SOC group, if followed by routine cardiac consultations.Results2129 patients with mAS and asAS were divided into those followed in HVC (n=251) versus SOC group (n=1878). The mean age was 76.5±12.4 years; 919 (43.2%) had asAS. During a follow-up of 4.8±1.8 years, 822 patients (38.6%) died, 307 (14.4%) were hospitalised for heart failure and 596 (28%) underwent aortic valve replacement (AVR). After propensity score matching, the number of consultations per year, exercise stress tests, brain natriuretic peptide (BNP) determinations and CTs were higher in the HVC cohort (p<0.05 for all). A shorter time between indication of AVR and less advanced New York Heart Association class was reported in the HVC cohort (p<0.001 and p=0.032). Compared with SOC, the HVC approach was associated with reduced all-cause mortality (HR=0.63, 95% CI 0.40 to 0.98, p=0.038) and cardiovascular death (p=0.030). At multivariable analysis, the HVC remained an independent predictor of all-cause mortality (HR=0.54, 95% CI 0.34 to 0.85, p=0.007).ConclusionsIn patients with mAS and asAS, the HVC approach was associated with more efficient management and outcome benefit compared with SOC.

BackgroundDevelopment of left ventricle (LV) hypertrophy in aortic stenosis (AS) is accompanied by adaptive coronary flow regulation. We aimed to assess absolute coronary flow, microvascular resistance, coronary flow reverse (CFR) and microvascular resistance reserve (MRR) in patients with and without AS.MethodsAbsolute coronary flow and microvascular resistance were measured by continuous thermodilution in 29 patients with AS and 29 controls, without AS, matched for age, gender, diabetes and functional severity of epicardial coronary lesions. Myocardial work, total myocardial mass and left anterior descending artery (LAD)-specific mass were quantified by echocardiography and cardiac-CT.ResultsPatients with AS presented a significantly positive LV remodelling with lower global longitudinal strain and global work efficacy compared with controls. Total LV myocardial mass and LAD-specific myocardial mass were significantly higher in patients with AS (p=0.001). Compared with matched controls, absolute resting flow in the LAD was significantly higher in the AS cohort (p=0.009), resulting into lower CFR and MRR in the AS cohort compared with controls (p<0.005 for both). No differences were found in hyperaemic flow and resting and hyperaemic resistances. Hyperaemic myocardial perfusion (calculated as the ratio between the absolute coronary flow subtended to the LAD, expressed in mL/min/g), but not resting, was significantly lower in the AS group (p=0.035).ConclusionsIn patients with severe AS and non-obstructive coronary artery disease, with the progression of LV hypertrophy, the compensatory mechanism of increased resting flow maintains adequate perfusion at rest, but not during hyperaemia. As a consequence, both CFR and MRR are significantly impaired.

Endomyocardial biopsy (EMB) facilitates a histopathologic diagnosis with unique prognostic and therapeutic implications in both native and donor hearts. It is a relatively safe procedure, with an overall complication rate ranging from <1% to 6% depending on the experience of the operator, the clinical status of the patient, the presence or absence of left bundle branch block, the access site, and the site of procurement (right ventricular [RV] vs left ventricular [LV] approach).

The Mustard and Senning operations for dextro-transposition of the great arteries (D-TGA) establish a biventricular physiology with a subaortic right ventricle (sRV). While prolonged QRS has been associated with worse prognosis in these patients, current echocardiographic tools fall short in adequately assessing the (mal)performance and function decline of the sRV during follow-up. The present study is the first to characterize Myocardial Work (MW) indices of the sRV in D-TGA patients after Mustard/Senning repair.

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Background The effect of adherence to cardiac rehabilitation (CR) on outcome is not clear. Therefore, we aimed to assess the impact of drop-out for non-medical reasons of CR on event-free survival in coronary artery disease (CAD).Methods A total of 876 patients who attended CR after acute coronary syndrome (ACS), percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) were included. Drop-out was defined as attending ≤50% of the training sessions. A combined endpoint of all-cause mortality and rehospitalization for a cardiovascular event was used to specify event-free survival. Differences in clinical characteristics were assessed and parameters with p< 0.10 were entered in a multiple Cox regression analysis.Results A total of 15% died or had a cardiovascular event during a median follow-up period of 33 months (interquartile range 24, 51). Overall, 17% dropped out before finishing half of the program. Patients who withdrew prematurely had a risk twice as high for a cardiovascular event or death (hazard ratio 1.92, 95% confidence interval 1.28–2.90) than those who attended more than half of the sessions. Both ACS (2.36, 1.47–3.58) and PCI (2.20, 1.22–3.96), as primary indicators for CR, were associated with an adverse outcome and also a prior history of chronic heart failure (CHF) remained negatively associated with event-free survival (3.67, 1.24–10.91). Finally, the presence of hyperlipidemia was independently related to a worse outcome (1.48, 1.02–2.16).Conclusions Drop-out for non-medical reasons was independently associated with a negative outcome in CAD. Therefore, underlying factors for drop-out should gain more attention in future research and should be taken into account when organizing CR.

ABSTRACTBackground:Left ventricular (LV) dilatation and remodeling following acute myocardial infarction increases wall stress, ventricular volumes and leads to heart failure (HF), which is associated with a high mortality. Percutaneous ventricular restoration (pVR) therapy reduces LV volumes leading to a more effective ejection. This study investigated the hemodynamic effects of LV volume reduction from pVR on LV performance and its interaction with the arterial system.Methods:Ten patients with symptomatic ischemic HF of New York Heart Association (NYHA) classes II to IV with LV antero-apical wall motion abnormalities underwent Parachute implantation. Pressure-volume loops were recorded immediately pre- and post-pVR implantation and at 6-month follow up.Results:Parachute implantation significantly reduced end-diastolic volume index (from 112 ± 39 mL to 100 ± 41 mL; p< 0.05), with a greater relative reduction in end-systolic volume index (from 66 ± 33 mL to 56 ± 32 mL; p< 0.05) with an overall 7% increase in ejection fraction (from 38 ± 11 to 46 ± 14%; p< 0.05). Furthermore, there was an observed reduction in dyssynchrony index (from 20 ± 4 to 14 ± 6%; p <0.05) and enhanced contractile function (Ees) immediately post-procedure, sustained at 6-months (from 0.92 ± 0.27 mmHg/mL to 1.37 ± 0.52 mmHg/mL, p <0.05).Conclusion:This present study confirms positive hemodynamic effects of LV volume reduction using the Parachute percutaneous ventricular restoration device. The Parachute device improved synchronous contraction and enhanced ventricular-arterial interaction likely due to LV reverse remodeling.

Mitral regurgitation (MR) is the second most prevalent heart valve disease requiring surgery. Despite the evidence of unfavourable prognosis, around half of patients with severe MR are not referred for surgery due to high per-operative risk. MitraClip (Abbott Vascular-Structural Heart, Menlo Park, California, United States) implantation is an emerging percutaneous technique with edge-to-edge MV repair inspired by the Alfieri surgery. Favourable safety profile together with improvement of functional status and decrease of MR severity in high-surgical-risk patients have been demonstrated in randomized clinical trials and “real-world” registries for both primary and secondary MR. Our own data confirmed its safety and efficacy comparing to minimally invasive MV surgery in treatment of functional MR in population with severe systolic heart failure.

Cardiac damage (CD) staging enhances risk stratification in patients with clinically significant aortic stenosis (AS). We aimed to assess the prognostic value and reclassification rate of right heart catheterization (RHC) compared to echocardiography (TTE) in characterizing CD-staging at 3-year follow-up in patients with clinically significant AS; to identify patients that would benefit from RHC for prognostic stratification; to test the prognostic value of "combined" CD-staging.

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Background:As cardiac aTTR amyloidosis(aTTR-CM) is frequently underdiagnosed and missed, improved screening to enhance earlier diagnosis of the disease is essential. Recent observations have demonstrated that clinical clues related to the presence of aTTR-CM and additional predisposing or associated medical conditions derived from machine learning(ML) models may provide a systematic framework to increase the suspicion of aTTR-CM in heart failure(HF) pts.Objectives:The present study was set up to explore the use of a systematic framework to diagnose aTTR-CM in a real-world HF population.Methods:Between 2014 and 2018, 3035 HF pts (Age:74 ± 12 years; EF: 45 ± 19 %, male: 50 %) consecutively referred to a community HF clinic were assessed. Using targeted disease-specific electronic health record (EHR) models (Natural language processing/ LynxCare Inc., Leuven, Be) the prevalence and odds ratios for cardiac, non-cardiac, and combinations of both cardiac and non-cardiac phenotypes predictive for aTTR-CM were assessed.Results:101 pts((Age: 78.57 ± 9.17 years; EF 46 ±15 %, male: 40% ) were diagnosed with aTTR-CM. Besides HF and cardiomyopathy-related phenotypes, atrial fibrillation was the strongest cardiac predictor for aTTR-CM(prevalence:76 %, OR 2.95, 95% CI= 2.10, 4.14) whereas the strongest non-cardiac predictor was carpal tunnel syndrome(prevalence :21 %, OR 6.55, 95% CI= 7.21, 5.90). The combination of heart block, joint disorders, and combined systolic and diastolic HF was the highest combined phenotype in aTTR-CM(prevalence:16 %, ORR 2.63, 95% CI = 0.96, 3.28).Conclusion:On top of well-known diagnoses and phenotypes unique combinations of cardiac and non-cardiac phenotypes predict aTTR-CM In a real-world HF population. Therefore, if successfully employed in the EHR this strategy may identify aTTR-CM pts and lead to earlier detection of it by raising the suspicion of the diagnosis in HF pts.

AimsTreatment with percutaneous edge-to-edge mitral valve repair (Mitraclip®) has recently been recommended as an alternative to conventional mitral valve repair for high surgical risk patients with symptomatic severe mitral regurgitation (MR). In this study, we report the first use of Mitraclip® therapy in Belgium.Methods and resultsThis prospective registry includes 41 consecutive patients treated with the Mitraclip® in two Belgian centres from October 2010 to June 2013. Acute procedural success, in-hospital safety end points and clinical status were analysed on an intention-to-treat basis up to one year after the procedure. In addition, determinants of major adverse cardiac events (MACE, death, surgical mitral valve intervention, and rehospitalization for heart failure) were analysed.Acute procedural success (successful clip placement and reduction of colour Doppler flow MR to ≤ 2) was obtained in 32 patients (78%) and 18 of these patients received two clips. The primary safety end point was reached in 36 pts (88%): one patient died due to intracranial bleeding, there were three urgent surgical interventions and one severe access site bleeding. The MACE rate after one year was 41% (17 patients). There were 11 deaths (27%), six surgical interventions (15%) and 10 rehospitalizations for heart failure (24%). Additional subgroup analysis revealed that the one-year MACE rate was particularly high in patients with left ventricular ejection fraction (LVEF) < 25%: 62% vs. 36% in patients with LVEF ≥ 25% (P =0.05). At one year, MR ≤ 2+ and NYHA class ≤ 2 was present in 83% of the surviving patientsConclusionIn high-risk patients with functional MR, treatment with the Mitraclip®-device is a feasible and safe option resulting in improvement of MR severity and clinical symptoms. However, as MACE is high in some subgroups (e.g. LVEF < 25%), careful patient selection is crucial to ensure the maximum benefit from this new technique.

We report the case of a 62-year-old woman presenting with symptoms and findings of myocardial infarction and a left ventricular free wall rupture.Coronary angiography revealed a critical stenosis in the middle right coronary artery. A contrast left ventriculogram revealed extravasation of contrast through the inferolateral wall of the left ventricle.Left ventricular free wall rupture is a rare complication of acute myocardial infarction, occurring in approximately 2% of cases. It is often fatal because of the development of haemopericardium and tamponade.Some patients, like the one described in this case, may present with small leaks that might close spontaneously by epicardial fibrin deposits, thus selflimiting, without requiring surgical intervention. This patient received only intense medical treatment. Indeed, blood clots at the endocardial and theepicardial site of the rupture have often been identified, suggesting protection for further rupture.

Case Report and Potential Mechanism We describe a patient with hemodynamic deterioration and worsening mitral regurgitation related to right ventricular apex pacing. Time-dependent changes in papillary muscle contraction as well [...]

Small coronary vessels supply small myocardial territories. The clinical significance of small-vessel stenoses is therefore questionable. Moreover, percutaneous coronary intervention (PCI) of nonfunctionally significant lesions does not improve clinical outcome and might be associated with potential procedural or stent related risks. The aim of this study was to assess the clinical outcome of fractional flow reserve (FFR)-guided PCI in the treatment of small coronary vessel lesions as compared with an angio-guided PCI.

Hemodynamic monitoring using implantable devices may provide early warning of volume overload in patients with heart failure (HF). This study was designed to prospectively compare information from intrathoracic impedance monitoring and continuous right ventricular pressure measurements in patients with HF.

Coronary allograft vasculopathy is a severe complication of heart transplantation. In this paper, the authors used virtual histology intravascular ultrasound to characterize plaque burden and tissue composition over time in vessels of heart transplant recipients. Knowledge of the relationship between changes in plaque composition and clinical outcome might facilitate identification of high-risk patients who require more aggressive medical therapy.

Bone marrow (BM) cells may interact with coronary endothelium and modulate coronary atherosclerosis. We investigated the time course of coronary luminal loss and changes in conductance after intracoronary injection of enriched hematopoietic BM stem cells in patients with previous myocardial infarction (MI). Among 24 patients with acute MI, 13 were randomized to early (<7 days) and 11 to late (4 months) intracoronary injection of CD133+ cells after the infarction. Segmental quantitative coronary angiography and fractional flow reserve (FFR) measurements of the infarct-related (IR) artery (A) and contralateral artery (control) were performed. In the early group, at 4 months, cumulative luminal loss (LL) of the minimal luminal diameter (MLD) of the IRA distal to the stented segment was −0.39 (−0.51−0.10) mm (p < 0.05 vs. control). There was no further change in LL between 4 and 8 months [−0.09 (−0.26−0.15) mm]. In parallel, FFR decreased at 4 months [−0.16 (−0.26−0.001), p < 0.05 vs. control] but slightly increased from 4 to 8 months follow-up [+0.05 (−0.10−0.09)]. In the late group, LL of the MLD of the IRA distal to the stented segments was −0.12 (—0.47−0.07) mm (NS vs. control) at 4 months and further −0.07 (−0.25−0.05) mm (NS) between 4 and 8 months. At 8 months, the total LL of the MLD in the early and late group was only slightly higher compared to control [−0.34 (−0.48—0.16), −0.36 (−0.69—0.09), and −0.12 (−0.39−0.05) mm, respectively, NS]. Early intracoronary administration of hematopoietic BM stem cells in patients with previous MI is associated with accelerated luminal loss and reduced conductance of the infarct-related artery.

Cardiac stem cell therapy with bone-marrow-derived stem cells is a promising approach to facilitate myocardial regeneration after acute myocardial infarction or in congestive heart failure. The clinical data currently available seem to indicate that this approach is safe and is not associated with an increase in the number of adverse clinical events; nevertheless, the level of safety confidence is limited because of the small number of patients who have been treated and the absence of long-term clinical follow-up data. In order to establish the clinical safety of cardiac stem cell therapy, it will be necessary to collect additional data from both previous and ongoing clinical trials in subsets of patients relative to their background risk. Several conceptual safety concerns should also be addressed. These concerns relate to a number of operational mechanisms and include biological effects on differentiation, remote homing of transplanted stem cells, progression of atherosclerosis, and arrhythmias. The proactive scrutiny of these phenomena could eventually facilitate the translation of the promise of cardiac regeneration into a safe and effective therapy.

It is still unclear whether the timing of intracoronary stem cell therapy affects the therapeutic response in patients with reperfused myocardial infarction. The natural course of healing the infarction and the presence of putative homing signals within the damaged myocardium appear to favor cell engraftment during the transendothelial passage in the early days after reperfusion. However, the adverse inflammatory environment, with its high oxidative stress, might be deleterious if cells are administered too early after reperfusion. In addition, current studies use mostly unfractionated cells and it remains to be addressed whether specific cell types, and their enrichment, would be better suited to augmenting the recovery at later time points. Here we highlight several aspects of the timing of intracoronary stem cell therapy and focus on time-related questions that are relevant to the design of future experimental and basic studies.

Although most malignant tumours metastasize to the heart they rarely produce clinical symptoms. Cardiac metastasis of tumours arising from head and neck and particulary of the larynx are extremely rare. Herein we report an unusual case of successfully treated, advanced laryngeal carcinoma with subsequent late symptomatic metastatic disease to the heart. The patient discussed, developed a right ventricular intracavitary tumour with pseudo-infarct pattern on the ECG. Current litterature regarding incidence, diagnostic techniques, treatment modalities and survival rates of secondary heart tumours are reviewed.

Persistent left superior vena cava is usually asymptomatic and does not cause any physiological problems1. However it can severely complicate pacemaker implantation and render it sometimes impossible2. In this case report we describe the implantation of a biventricular pacemaker using a left-sided approach in a patient with persistent left superior vena cava syndrome. A biventricular resynchronization device was used because of the reported beneficial haemodynamic effects of this pacing mode in patients with severe heart failure3.

Introduction:Overexpression of serpin peptidase inhibitor, clade A member 3 (SERPINA3) has been associated with poor prognosis in cancer.Hypothesis:SERPINA3 in a de novoor worsened heart failure (HF) bears a prognostic information alone and in addition to established biomarkers NT-proBNP and ST2 or clinical risk factors.Methods:Circulating SERPINA3 levels were examined in HFpatients who died within 5 years (n=44) and compared with age- and hemodynamically matched survivors (n=39). Prognostic value of circulating SERPINA3 levels alone and in combination with ST2 and NT-proBNP was then analyzed in an independent cohort with a de novo or worsened HF (n=384).Results:Plasma SERPINA3 levels were significantly higher in HF non-survivors compared to survivors (334.7 ± 138.7 vs 228.2 ± 83.1 μg/mL, p<0.01). In the spline curve analysis,SERPINA3 level of 316 μg/mL emerged as optimal cut-off value for mortality. In the validation cohort with a de novoor worsened HF (n=384), circulating SERPINA3 levels >316 μg/mL were associated with increased all-cause mortality (HR (95% CI): 2.4 (1.5-3.9), p=0.0002) and its composite with unplanned cardiac admission (HR (95% CI): 2.0 (1.2-3.3), p=0.004). In a multivariate analysis, including established clinical risk factors and ST2 and NT-proBNP, SERPINA3 remained independent predictor of all-cause mortality together with age, ST2, glomerular filtration and pulmonary capillary wedge pressure.Conclusions:Elevated SERPINA3 appears to provide additional prognostic information in models incorporating clinical, hemodynamic and laboratory risk including ST2 and NT-proBNP by identifying a subgroup of heart failure patients at increased mortality risk.

Introduction:Heart failure (HF) is a heterogenous syndrome with complex pathophysiology. Biomarkers and clinical risk scores often fail to capture modifications in the treatment continuity and provide suboptimal patient-level precision in the prognostic stratification. Electronic patient records provide necessary granularity yielding opportunities to develop new artificial intelligence (AI) based strategies for comprehensive prognostic re-stratification.Hypothesis:We assessed the hypothesis that, utilizing longitudinal patient data in an AI approach, yields superior performance predicting all-cause mortality in a cohort of patients hospitalized with a de novoor worsened HF, compared to single observational time point predictions.Methods:In a cohort of 2449 HF patients hospitalized between 2011-2017, we utilized 151 451 patient exams from 422 parameters. Features included clinical phenotyping, medication, ECG, laboratory, echocardiography, catheterization data or percutaneous and surgical interventions gathered on a routine clinical basis reflecting standard of care as captured in individual electronic records. AI models were developed, and their performance on the validation set was compared to industry standard clinical scores.Results:AI models yielded performance ranging from 0.83 to 0.89 AUC on the outcome-balanced validation set in predicting all-cause mortality at 30-, 90-, 180-, 360- and 720-day time-limits. The primary endpoint, 1-year mortality prediction model, recorded 0.85 AUC on the validation set compared to 0.7 AUC (Seattle HF model) and 0.73 AUC (MAGGIC HF Score) respectively.Conclusions:Our findings present a novel, patient-level, AI-based risk prediction approach of all-cause mortality in heart failure utilizing all historical data available in electronic health records. This suggests the potential of AI based predictive models in a point-of-care approach to guide clinical risk stratification.

Objectives. In the present study, we investigated, in transplant recipients, whether l-arginine (l-arg) potentiates the myocardial contractile effects of receptor-mediated coronary endothelial stimulation. Moreover, because inducible nitric oxide synthase (iNOS) is frequently expressed in transplanted myocardium, we also performed intracoronary infusion of l-arg in the absence of receptor-mediated coronary endothelial stimulation to investigate whether similar left ventricular (LV) contractile effects could be induced by providing more substrate for iNOS.

The additional role of continuous monitoring of filling pressures and impedance in heart failure patients with chronic kidney disease remains undetermined. In this case report, the effects of diuretic therapy and renal replacement therapy by hemodialysis upon right ventricular filling pressures and impedance are described in a patient with end-stage heart failure and end-stage chronic kidney disease (grade 5). We demonstrated that unloading of the heart by hemodialysis partly restored the blunted Frank-Starling relationship.

Although pericardial eff usion is a well-known feature of Churg-Strauss syndrome, cardiac tamponade has rarely been encountered. The present report describes a case of Churg-Strauss syndrome that presented as an acute cholecystitis and was complicated by tamponade. Histopathological exam of both pericardium and gall bladder was conclusive for Churg-Strauss syndrome.

The advent of biventricular devices has added new complexity to the evaluation of pacemaker function and follow-up. Consequently one must acknowledge the various circumstances that can disrupt ventricular resynchronization and provoke haemodynamic deterioration1. In this paper we report upon haemodynamic deterioration following resynchronization therapy because of an erroneous connection of an epicardial right ventricular (RV) outflow tract lead to the left ventricular (LV) channel of the device. How ECG and echocardiography can guide the diagnosis and help in prematurely detecting abnormal pacing or loss of LV capture is discussed in detail below.

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Supplemental Digital Content is available in the text.

Introduction:In patients with heart failure and preserved ejection fraction (HFPEF), even mild secondary mitral regurgitation (MR) has been associated with poor outcomeHypothesis:To test the hypothesis that, in patients with non-ischemic HFPEF and secondary MR, endoscopic MVRepair will be associated with improved outcome compared with standard-of-care (StanCare) management.Methods:The MVRepair group consisted of 143 consecutive patients (age 72?7 y, 24% males) with HFPEF and secondary MR who underwent endoscopic MVRepair. The StanCare group consisted of 143 consecutive patients (age 78?9 y, 29% males) with HFPEF admitted for first decompensation. To be eligible for the study, all patients had to have normal LVEF (?50%), H2FPEF score ? 5 and secondary MR. Patients with coronary artery disease or primary MR were excluded. One to one propensity score matching was performed. Primary endpoint was all-cause mortality and HFPEF readmission (time to first event).Results:During median follow up of 4.4 years [IQR 2.2-7.9], significantly more patients had primary endpoint (29% vs 58%, Log-rank p<0.001), died (43% vs 22%, Log-rank p<0.01) or had HFPEF readmission (34% vs 10%, Log-rank p<0.001) in the StanCare versus the MVRepair group (Figure). In Cox regression analyses adjusted for age, MVRepair was the only independently associated with primary endpoint (HR 0.16; 95% CI 0.10-0.27; p<0.001), all-cause mortality (HR 0.25; 95% CI 0.12-0.54; p<0.001) or HFPEF readmissions (HR 0.18; 95% CI 0.09-0.36; p<0.001).In the propensity matched cohort, MVRepair compared with StanCare showed 29% (SE 8.9%) absolute risk reduction of primary endpoint (p 0.001).Conclusions:In HFPEF patients with secondary MR, minimally invasive surgical MVRepair seems to be associated with improved outcome compared to standard of care management.

Introduction:A pulmonary capillary wedge pressure (PCWP) ? 25 mm Hg following volume load or exercise has been proposed as a partition value for detection of HfpEF. However, the hemodynamic response to volume challenge in heart transplant (Tx) recipients has never been studied.Methods:24 heart Tx recipients (Age: 65 ? 14 years) with normal LV function (55 ? 7 %) and without rejection and graft vasculopathy underwent right heart catheterization to measure hemodynamic response to volume loading before and after a rapid saline infusion of 7mL/kg over 10 min. PCWP, right atrial pressure (RAP), mean pulmonary artery pressure(PA) were obtained and the PCWP and indexed(i) stroke volume(SV) data were used to construct Starling (SVindex/PCWP) curves. Pts were categorized in those with elevated filling pressures (Group A, n=13 pts) defined by a PCWP ? 15 mm Hg at rest or ? 25 mm Hg following volume loading vs those without (Group B, n=11 pts).Results:No difference in age of donor and transplant, baseline hemodynamics and EF was noted between both groups. Group A(n= 13pts) and group B pts (n= 11pts). Saline infusion significantly increased PCWP and mean PA in both Groups (table 1) without any significant change in BP and heart rate. Interestingly saline infusion was associated with a significant rise in SV and SVi in GroupB not in GroupA pts. Moreover, in GroupB pts the Starling curves revealed a larger SVi at any give PCWP compared to GroupA pts(Fig.1).Conclusions:In the transplanted heart volume loading increases filling pressures and is able to unmask left ventricular diastolic dysfunction. Interestingly, those with HFpEF are characterized by a blunted Frank Starling response as evidenced by higher PCWP and failure to increase SV for any given PCWP. Further prospective studies are warranted to unravel the underlying mechanisms.