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Heart failure (HF) is a debilitating disease with 26 million patients worldwide. Consistent and complex self-care is required on the part of patients to adequately adhere to medication and to the lifestyle changes that the disease necessitates. Mobile health (mHealth) is being increasingly incorporated in patient interventions in HF, as smartphones prove to be ideal platforms for patient education and self-help assistance. This systematic review aims to summarize and report on all studies that have tested the effect of mHealth on HF patient outcomes. Our search yielded 17 studies, namely 11 randomized controlled trials and six non-randomized prospective studies. In these, patients with the assistance of an mHealth intervention regularly measured their blood pressure and/or body weight and assessed their symptoms. The outcomes were mostly related to hospitalizations, clinical biomarkers, patients' knowledge about HF, quality of life (QoL) and quality of self-care. QoL consistently increased in patients who received mHealth interventions, while study results on all other outcomes were not as ubiquitously positive. The first mHealth interventions in HF were not universally successful in improving patient outcomes but provided valuable insights for patient-oriented application development. Future trials are expected to build on these insights and deploy applications that measurably assist HF patients., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Hellenic Society of Cardiology. Published by Elsevier Inc. All rights reserved.)

The left ventricular (LV) ejection fraction (LVEF), despite its severe limitations, has had an epicentral role in heart failure (HF) classification, management, and risk stratification for decades. The major argument favoring the LVEF based HF classification has been that it defines groups of patients in which treatment is effective. However, this reasoning has recently collapsed, since medical treatment with neurohormonal inhibitors, has proved beneficial in most HF patients regardless of the LVEF. In addition, there has been compelling evidence, that the LVEF provides poor guidance for device treatment of chronic HF (implantation of cardioverter defibrillator, cardiac resynchronization therapy) since sudden cardiac death may occur and cardiac dyssynchronization may be disastrous in all HF patients. The same holds true for LV assist device implantation, in which the LVEF has been used as a surrogate for LV size. In this review article we update the evidence questioning the use of LVEF-based HF classification and argue that guidance of chronic HF treatment should transition to more contemporary concepts. Specifically, we propose an etiologic chronic HF classification predominantly based on epidemiological data, which will be foundational for further higher resolution phenotyping in the emerging era of precision medicine., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Heart failure with reduced ejection fraction (HFrEF) is a complex clinical syndrome with significant morbidity and mortality and seems to be responsible for approximately 50% of heart failure cases and hospitalizations worldwide. First-line treatments of patients with HFrEF, according to the ESC and AHA guidelines, include β-blockers, angiotensin receptor/neprilysin inhibitors, sodium-glucose cotransporter 2 inhibitors, and mineralocorticoid receptor antagonists. This quadruple therapy should be initiated during hospital stay and uptitrated to maximum doses within 6 weeks after discharge according to large multicenter controlled trials. Quadruple therapy improves survival by approximately 8 years for a 55-year-old heart failure patient. Additional therapeutic strategies targeting other signaling pathways such as ivabradine, digoxin, and isosorbide dinitrate and hydralazine combination for African Americans, as well as adjunctive symptomatic therapies, seem to be necessary in the management of HFrEF. Although second-line medications have not achieved improvements in mortality, they seem to decrease heart failure hospitalizations. There are novel medical therapies including vericiguat, omecamtiv mecarbil, genetic and cellular therapies, and mitochondria-targeted therapies. Moreover, mitraclip for significant mitral valve regurgitation, ablation in specific atrial fibrillation cases, omecamtiv mecarbil are options under evaluation in clinical trials. Finally, the HeartMate 3 magnetically levitated centrifugal left ventricular assist device (LVAD) has extended 5-year survival for stage D HF patients who are candidates for an LVAD.

Several attempts have been made, by the scientific community, to develop a unifying hypothesis that explains the clinical syndrome of heart failure (HF). The currently widely accepted neurohormonal model has substituted the cardiorenal and the cardiocirculatory models, which focused on salt-water retention and low cardiac output/peripheral vasoconstriction, respectively. According to the neurohormonal model, HF with eccentric left ventricular (LV) hypertrophy (LVH) (systolic HF or HF with reduced LV ejection fraction [LVEF] or HFrEF) develops and progresses because endogenous neurohormonal systems, predominantly the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system (RAAS), exhibit prolonged activation following the initial heart injury exerting deleterious hemodynamic and direct nonhemodynamic cardiovascular effects. However, there is evidence to suggest that SNS overactivity often preexists HF development due to its association with HF risk factors, is also present in HF with preserved LVEF (diastolic HF or HFpEF), and that it is linked to immune/inflammatory factors. Furthermore, SNS activity in HF may be augmented by coexisting noncardiac morbidities and modified by genetic factors and demographics. The purpose of this paper is to provide a contemporary overview of the complex associations between SNS overactivity and the development and progression of HF, summarize the underlying mechanisms, and discuss the clinical implications as they relate to therapeutic interventions mitigating SNS overactivity., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Regardless of the currently proposed best medical treatment for heart failure patients, the morbidity and mortality rates remain high. This is due to several reasons, including the interaction between oral cardiac drug administration and gut microbiota. The relation between drugs (especially antibiotics) and gut microbiota is well established, but it is also known that more than 24% of non-antibiotic drugs affect gut microbiota, altering the microbe's environment and its metabolic products. Heart failure treatment lies mainly in the blockage of neuro-humoral hyper-activation. There is debate as to whether the administration of heart-failure-specific drugs can totally block this hyper-activation, or whether the so-called intestinal dysbiosis that is commonly observed in this group of patients can affect their action. Although there are several reports indicating a strong relation between drug-gut microbiota interplay, little is known about this relation to oral cardiac drugs in chronic heart failure. In this review, we review the contemporary data on a topic that is in its infancy. We aim to produce scientific thoughts and questions and provide reasoning for further clinical investigation.

Nonischemic cardiomyopathy (NICM) is a significant cause of cardiogenic shock (CS). We present a case of a 56-year-old previously healthy man who arrived with vague abdominal symptoms, over 2 weeks. Subsequently, the patient's condition rapidly deteriorated over 12 hours, leading to cardiogenic shock categorized as Society for Cardiovascular Angiography and Interventions (SCAI) stage D. Echocardiography and right heart catheterization confirmed multiorgan failure secondary to severe cardiac dysfunction. Mechanical circulatory support was initiated using an Impella CP device 20 hours after admission due to ongoing deterioration. Considering refractory cardiogenic shock and within 24 hours, the patient received combined veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and Impella CP support (ECPElla). With gradual improvement in the patient's clinical status and organ function, successful weaning from VA ECMO to Impella 5.5 was achieved. Ultimately, the patient underwent a successful orthotopic heart and kidney transplantation, marking a significant milestone in his recovery. The case underscores the importance of promptly identifying and responding to cardiogenic shock through invasive hemodynamic assessment. Collaborative decision-making involving a multidisciplinary team played a crucial role in the initiation, escalation, and eventual weaning of mechanical circulatory support, culminating in the successful bridging to a dual organ transplantation for this patient with CS secondary to NICM., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Inflammation is a major component of heart failure (HF), causing peripheral vasculopathy and cardiac remodeling. High levels of circulating inflammatory cytokines in HF patients have been well recognized. The hallmark of the inflammatory imbalance is the insufficient production of anti-inflammatory mediators, a condition that leads to dysregulated cytokine activity. The condition progresses because of the pathogenic consequences of the cytokine imbalance, including the impact of endothelial dysfunction and adrenergic responsiveness deterioration, and unfavorable inotropic effects on the myocardium. Hence, to develop possible anti-inflammatory treatment options that will enhance the outcomes of HF patients, it is essential to identify the potential pathophysiological mechanisms of inflammation in HF. Inflammatory mediators, such as cytokines, adhesion molecules, and acute-phase proteins, are elevated during this process, highlighting the complex association between inflammation and HF. Therefore, these inflammatory markers can be used in predicting prognosis of the syndrome. Various immune cells impact on myocardial remodeling and recovery. They lead to stimulation, release of alarmins and risk-related molecule patterns. Targeting key inflammatory mechanisms seems a quite promising therapy strategy in HF. Cytokine modulation is only one of several possible targets in the fight against inflammation, as the potential molecular targets for therapy in HF include immune activation, inflammation, oxidative stress, alterations in mitochondrial bioenergetics, and autophagy.

Background: United Network for Organ Sharing (UNOS) allocation criteria changed in 2018 to accommodate the increased prevalence of ventricular assist device use as a bridge to heart transplant, which consequently prioritized sicker patients. We aimed to assess the impact of this new allocation policy on the length of stay following heart transplantation. Secondary outcomes include other risk factors for prolonged hospitalization and its effect on mortality and postoperative complications., Methods: The UNOS Registry was queried to identify patients who underwent isolated heart transplants in the United States between 2001 and 2023. Patients were divided into quartiles according to their respective length of stay., Results: A total of 57 020 patients were included, 15 357 of which were allocated with the new system. The median hospital length of stay was 15 days (mean 22.7 days). Length of stay was longer in the new allocation era (25 ± 30 vs. 22 ± 27 days, p < .001). The longer length of stay was associated with increased 5-year mortality in the new allocation system (aHR: 1.18; 95% CI: 1.15, 1.20; p-value: < .001)., Conclusion: Longer hospital stays and associated observed increased risk for mortality in the era after the allocation criteria change reflect the rationale of this shift which was to prioritize heart transplants for sicker patients. Further studies are needed to track the progress of surgical and perioperative management of these studies over time., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

This study aims to evaluate the difference between dobutamine and milrinone in patients presenting with acute decompensated heart failure (AHF). Inotropes are indicated for treating AHF, especially in patients with concomitant hypoperfusion indicative of cardiogenic shock. However, previous studies have not identified the optimal inotrope. We sought to compare outcomes associated with milrinone versus dobutamine in patients with AHF. A systematic literature search was performed to identify relevant trials from inception to August 2021. Our primary outcome of interest was mortality. Analysis was sub-categorized according to subpopulation, including AHF, AHF with cardiogenic shock (AHF-shock), AHF with a bridge to transplantation, and AHF with destination therapy. Summary effects were calculated using a fixed-effects model as risk ratio or mean difference with 95% confidence intervals for all the clinical endpoints. Ten studies, including one randomized controlled trial with 21,106 patients, were included in the analysis (4918 patients were in the Milrinone group, while 15188 were in the Dobutamine group). Milrinone was associated with a lower risk of mortality in patients with AHF (relative risk 0.87; confidence interval :0.79-0.97; P < 0.05, heterogeneity I² = 0%) with event rates of 9.4% vs 9.8% (number needed to treat of 250). Milrinone was also associated with improved mortality with relative risk 0.76 (0.79-0.95; P < 0.05) in patients with AHF with destination therapy. There was a non-significant trend towards improved mortality in AHF-shock patients. However, AHF with a bridge to transplantation patients had a non-significant trend towards improved mortality with dobutamine. There was no difference between the 2 strategies for the outcomes of acute kidney injury, initiation of renal replacement therapy, mechanical ventilation, arrhythmias, symptomatic hypotension, and length of hospital stay in the overall population. Intensive care unit length of hospital stay was lower in AHF-shock patients in the milrinone group, whereas dobutamine was associated with a lower length of intensive care unit stay in AHF patients. The cumulative data comparing milrinone with dobutamine indicate an overall marginal benefit of milrinone compared to dobutamine in the totality of patients with AFH with or without cardiogenic shock, and whether or not they are bridged to transplantation or destination assist device. More appropriately powered prospective studies are needed to identify a conclusive benefit of one inotrope over another., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Cardiac graft failure may require repeat heart transplantation (HTx). Outcomes of patients that undergo repeat HTx have not been well described. We compared patients that received repeat HTx with patients that received initial HTx by inquiring the United Network for Organ Sharing (UNOS) database between 2015 and 2021. The primary endpoint was all-cause mortality, while the role of baseline characteristics was also investigated. Patients were stratified according to whether they received initial HTx (n = 19,727, 97%) or repeat HTx (n = 578, 3%). Among the study population, 10,860 (53.5%) patients received a HTx using the old UNOS allocation system, whereas 9445 (46.5%) patients received a HTx after the implementation of the new UNOS donor allocation system in October 2018. In this sub-group of HTx recipients in the new allocation system era, the adjusted 1-year survival of repeat HTx patients remained lower than that of initial HTx patients (hazard ratio (HR): 1.19; 95% confidence interval (CI): 1.15, 3.18; p = 0.013). When we compared the 1-year survival of repeat HTx patients before and after the implementation of the new allocation system, the adjusted 1-year survival was similar between groups (HR: 1.14; 95% CI: 0.71, 1.84; p = 0.591). The unadjusted risk of 30-day mortality was not significantly different in the new vs old allocation system. Mortality associated with repeat HTx remained higher than initial HTx but the new donor allocation system implementation did not affect outcomes.

There are limited data on the frequency of diagnosis of infectious disease and its impact on patients hospitalized with decompensated heart failure. We sought to evaluate the prevalence, types, trends, and outcomes of infectious disease diagnosis in patients admitted with decompensated heart failure. We performed a retrospective cohort study in patients admitted with a primary diagnosis of heart failure using the National Inpatient Sample database from 2009 to 2019. Patients with a length of stay ≥3 days were included. Patients with chronic dialysis, left ventricular assist devices, cardiogenic shock, or solid organ transplantation or who required mechanical ventilation or mechanical circulatory support were excluded. Patients were stratified according to the presence or absence of infectious disease diagnosis. Outcomes of interest were in-hospital mortality, length of stay, and resource utilization. Among the 7,228,521 admissions with a primary diagnosis of heart failure that met the inclusion and exclusion criteria, an infectious disease diagnosis was reported in 1,806,514 (24.9%). Infectious disease diagnosis was more frequent in patients who were female, older, and White, and who had higher baseline co-morbidity. Since 2014, there has been a steady decrease in infectious conditions in patients admitted with a primary diagnosis of heart failure (p for trend <0.01). After propensity match analysis was performed, patients with infectious disease diagnosis had a longer length of stay (6.9 vs 5.7 days, p <0.001) and higher cost ($14,305 vs $11,760, p <0.001), were less likely to be discharged home (35.3% vs 44.7%, p <0.001), and had higher in-hospital mortality (2.6% vs 1.6%, p <0.001). In conclusion, approximately 1 in 4 patients admitted with primary heart failure will be diagnosed with an infectious condition. The presence of an infectious disease diagnosis is associated with increased morbidity and mortality., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Patients on the waiting list for heart transplantation (HT) can become inactive or made status seven because of medical reasons, such adverse events, complications, or psychosocial circumstances. If the condition that caused the inactivation is resolved, patients are re- activated. Information about the prognostic implications of Status 7 in the new donor heart allocation system has not been described. To bridge this knowledge gap, we performed an analysis of the United Network of Organ Sharing (UNOS) registry., Methods: Data on adult patients who underwent HT between October 18th, 2018 and October 2021, were queried from the UNOS registry. The main outcomes were post- transplant all-cause mortality, 1-year all-cause mortality and treated acute rejection. Since re-transplantation is a competing event for all-cause mortality, we performed competing risk survival analysis and reported sub distribution hazard ratios (SHR) from the Fine and Gray model to examine the relationship between inactive status and all-cause mortality., Results: A total of 5267 adult patients underwent HT and were previously listed as Status 1 or Status 2 in the new allocation system. We identified 946 HT recipients temporarily inactivated while on HT list (18%). The number of temporarily inactive patients remained stable since the implementation of the new donor allocation system (p = .37). Approximately, two-thirds of temporarily inactive patients (65.9%) were inactivated for being too sick, whereas other frequent justifications for inactivity included left ventricular assist device implantation (7.8%) and insurance related issues (4.8%). Temporarily inactive HT recipients were more likely to be African Americans, males, have a higher body mass index (BMI) and significantly longer waiting time (391.6 ± 600 vs. 72.3 ± 223 days, p < .001) compared with never inactivated patients. In the unadjusted analyses 30-day mortality did not differ between groups, but both 1-year and overall all-cause mortality was significantly higher in temporarily inactive patients (1-year: SHR: 1.3; 95% confidence intervals [CI]: 1.03, 1.64; p = .028, overall mortality SHR: 1.31; 95% CI: 1.06, 1.64; p = .014). After adjustment for donor and recipient characteristics, a trend towards higher 1-year and overall mortality remained (1-year: SHR 1.32; 95% CI .99, 1.76, p = .006, overall mortality SHR: 1.29; 95% CI: .98-1.68, p = .065). No differences in treated acute allograft rejection at 1 year were found between groups., Conclusions: Temporary inactive status while waiting for HT occurs in approximately one in five HT recipients listed in higher urgency categories after the implementation of the new allocation system. A signal of adverse long-term outcomes was found, and this could be explained by differences in recipient characteristics. Further research is required to elucidate pathways involved and possible implications for clinical practice., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Cardiogenic shock (CS) presents with a complex spectrum of low output states, which can be provoked by Acute Coronary Syndrome (ACS) or Acute Decompensated Heart Failure (ADHF). Its management includes hemodynamic assessment via right heart catheterization (RHC). Herein, we describe the timing of RHC based on the etiology and severity of CS as defined by the Society of Cardiovascular Angiography & Interventions (SCAI) Shock Classification. We performed a single-center retrospective analysis of patients admitted with CS secondary to ACS or ADHF from January 7, 2018 to June 30, 2020 at the University of Iowa Hospitals and Clinics. Among the 647 patients admitted, 249 patients had RHC during their admission. Of those, 51 had underlying ACS and 198 had ADHF. The overall time from admission to invasive hemodynamic assessment was 2.73 days. The mean time for SCAI-A was 3.6 ± 2.8 days, SCAI-B 3.7 ± 3.7 days, SCAI-C 2.6 ± 3.0 days, SCAI-D 2.5 ± 4.1 days, and SCAI-E 1.3 ± 2.1 days. The linear regression model showed that RHC was performed earlier in patients with worse hemodynamics evaluated by Cardiac Power Output (CPO) (Coefficient 0.14, R- squared 0.01, P = 0.03). Hemodynamic parameters showed that high PAPi, RVSWi, and Cardiac Power Output during admission predicted low in-hospital mortality (P < 0.01). RHC was performed earlier in more critically ill patients. Patients with CS in the setting of ACS underwent RHC significantly earlier than those with ADHF., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Despite advances in temporary mechanical circulatory support (TMCS), in-hospital mortality and morbidity related to cardiogenic shock due to ST elevation myocardial infarction (CS-STEMI) are highly prevalent. We identified admissions with CS-STEMI between 2016 and 2019 from the National Readmission Database (NRD). Among 80 997 patients with CS-STEMI, we identified 42,139 without TMCS, while the remaining received various types of TMCS (Extra corporeal membrane oxygenation [ECMO] alone: n = 753; Intra-aortic balloon pump [IABP] alone: n = 27 556; Impella alone: n = 9055; ECMO with IABP or Impella: n = 1494). 30-day readmission rates did not differ among groups, whereas 90-day readmissions were higher among those with combined ECMO and IABP or Impella support ( P = .027). In-hospital mortality and complications including hemodialysis, transfusion, and stroke were the highest in the Impella and combined ECMO and IABP/Impella groups. Heart failure was the most common cause of readmission. Multivariable logistic regression revealed female gender, diabetes, prior myocardial infarction, heart failure, chronic kidney, and peripheral artery disease as risk factors for 90-day readmissions. Our study unveiled several important factors associated with readmission and mortality related to TMCS in CS-STEMI. Approaches to identify and prevent readmissions by addressing these factors may lead to lower morbidity, healthcare cost related to readmission, and improved quality of life.

Background: High-output heart failure (HOHF) is an underdiagnosed type of heart failure (HF) characterized by low systemic vascular resistance and high cardiac output., Objective: This study sought to characterize the causes, mortality, and readmissions related to HOHF within the United States., Methods: Data were collected from the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project (HCUP) National Readmissions Database (NRD) from January 1, 2017, to November 30, 2019. We used the International Classification of Diseases, 10th revision (ICD-10), diagnostic codes to identify encounters with HOHF and heart failure with reduced ejection fraction (HFrEF)., Results: Of the total 5,080,985 encounters with HF, 3,897 hospitalizations (mean age 62.5 ± 17.9 years, 56.5% females) with HOHF and 5,077,088 hospitalizations with HFrEF were recorded. The most commonly associated putative etiologies of HOHF included pulmonary disease (19.8%), morbid obesity (9.9%), sepsis (9.6%), cirrhosis (8.9%), myelodysplastic syndrome (MDS) (7.9%), hyperthyroidism (5.5%), and sickle cell disease (3.3%). There was no significant difference in mortality rates [4.3% vs. 5.2%; odds ratio (OR) 0.9, 95% confidence interval (CI) 0.7-1.2] between HOHF and HFrEF. However, the 30-day readmission rate for HOHF was significantly lower than that for HFrEF (5.7% vs. 21.2%; OR 0.39, 95% CI 0.30-0.51). Cardiovascular (39.9%) followed by hematological (20.6%) complications accounted for the majority of 30-day readmissions in the HOHF group., Conclusions: HOHF is an infrequently reported cardiovascular complication associated with noncardiovascular disorders and is encountered in 0.07% of all encounters with HF. Although comparable in-hospital mortality between studied cohorts was observed, raising awareness and timely recognition of this entity are warranted., (Copyright © 2022 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.)

Background: Machine learning (ML) is increasingly being applied in Cardiology to predict outcomes and assist in clinical decision-making. We sought to develop and validate an ML model for the prediction of mortality after heart transplantation (HT) in adults with congenital heart disease (ACHD)., Methods: The United Network for Organ Sharing (UNOS) database was queried from 2000 to 2020 for ACHD patients who underwent isolated HT. The study cohort was randomly split into derivation (70%) and validation (30%) datasets that were used to train and test a CatBoost ML model. Feature selection was performed using SHapley Additive exPlanations (SHAP). Recipient, donor, procedural, and post-transplant characteristics were tested for their ability to predict mortality. We additionally used SHAP for explainability analysis, as well as individualized mortality risk assessment., Results: The study cohort included 1033 recipients (median age 34 years, 61% male). At 1 year after HT, there were 205 deaths (19.9%). Out of a total of 49 variables, 10 were selected as highly predictive of 1-year mortality and were used to train the ML model. Area under the curve (AUC) and predictive accuracy for the 1-year ML model were .80 and 75.2%, respectively, and .69 and 74.2% for the 3-year model, respectively. Based on SHAP analysis, hemodialysis of the recipient post-HT had overall the strongest relative impact on 1-year mortality after HΤ, followed by recipient-estimated glomerular filtration rate, age and ischemic time., Conclusions: ML models showed satisfactory predictive accuracy of mortality after HT in ACHD and allowed for individualized mortality risk assessment., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Concerns about the impact of the new donor heart allocation system on posttransplant outcomes have emerged after its implementation. We sought to evaluate the characteristics and outcomes of left ventricular assist device (LVAD) recipients transplanted before and after the implantation of the new policy on October 18, 2018., Methods: Data on bridge to transplantation of adult patients with LVAD between January 2015 and October 2021, with durable LVAD as a (BTT), was queried from the United Network of Organ Sharing (UNOS) registry. The main outcomes were 30-day all-cause mortality, 30-day fatal graft failure, 1-year all-cause mortality, treated acute rejection at 1 year and renal replacement therapy (RRT) for acute renal failure., Results: In our study, 7096 patients met the inclusion criteria including 2435 in the new allocation system. The transplanted patients in the new allocation system era had older donor age, longer ischemic time, and higher proportion of newer generation LVADs. Adjusted 30-day all-cause mortality was significantly lower for LVAD recipients in the new allocation system era (2.5% vs. 3.6%; sub-hazard ratio [SHR] 0.36, 95% Confidence intervals [CI] 0.27-0.48, p < 0.001) without differences in the risk of fatal graft failure and 1-year mortality (7.8% vs. 9.6%). Significantly lower adjusted 30-day mortality with HVAD and HM3 devices than HM2 in the new allocation system era was found, without differences in 1-year mortality. Acute allograft rejection requiring treatment was significantly lower (Odds Ratio 0.78, 95% CI 0.65-0.94, p = 0.01), whereas a trend toward higher risk of renal failure requiring RRT was identified., Conclusions: Despite changing donor characteristics and longer ischemic times, posttransplant outcomes in LVAD recipients have not worsened with the implementation of the new allocation system and this finding is related to the use of newer generation continuous flow LVADs., (© 2022 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Background: The impact of wild-type transthyretin-related cardiac amyloidosis (ATTRwt) on functional and structural peripheral vascular measures is unknown. In the present study, we explored patterns of vascular dysfunction in patients with ATTRwt in comparison to diseases with similar cardiac phenotype., Methods: Treatment-naïve patients with ATTRwt (n = 32) were compared to: 1. Age-and sex-matched reference population without amyloidosis (n = 32), 2. Age-and sex-matched patients with systemic AL amyloidosis (n = 32), and 3. patients with cardiac AL amyloidosis (AL-HF, n = 23) or elderly patients with heart failure with preserved ejection fraction (HFpEF) (n = 16). All subjects underwent peripheral vascular assessment using carotid artery ultrasonography, brachial artery flow-mediated dilation (FMD), measurement of arterial stiffness and aortic hemodynamics including heart rate-adjusted time of return of reflected waves (Tr/HR)., Results: After adjustment for traditional cardiovascular risk factors and coronary artery disease (core model), peripheral and aortic blood pressures (BP) were lower in patients with ATTRwt (p < 0.05) whereas other vascular markers were preserved compared to the reference non-amyloidosis group. ATTRwt was independently associated with lower BP and longer Tr/HR compared to AL. Compared to AL-HF, FMD was lower in ATTRwt (p = 0.033). ATTRwt patients had lower BP and higher Tr/HR than HFpEF (p < 0.05). By ROC analysis, Tr/HR discriminated ATTRwt vs. AL-HF (sensitivity 93%, specificity 75%) and HFpEF (sensitivity 100%, specificity 94%) and lower FMD increased the likelihood for ATTRwt at low Tr/HR values., Conclusion: ATTRwt patients present a distinct peripheral vascular fingerprint which is different from AL-HF or HFpEF, consisting of lower peripheral and aortic BP, prolonged Tr/HR and FMD at reference-population range., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: Heart failure (HF) is a common cause of morbidity and mortality in older patients. Frailty is prevalent and complicates the course of HF. We sought to investigate the impact of frailty on HF outcomes., Methods: Patients over 65 years old hospitalized with acute decompensated HF and mildly reduced or preserved EF, between September 2017 and September 2019 were enrolled in the study. Before hospital discharge at euvolemic state, patients underwent six-minute walk test (6MWT) and frailty assessment using FRIED and modified SOF scores. Predictors of death, readmissions, and increase in diuretic dose were analyzed by multivariable logistic regression models., Results: We enrolled 193 consecutive patients (mean age 78.6 ± 8.4 years, 29.5% males, 59.6% with HF and preserved EF). All patients had at least one comorbidity (40.9% coronary artery disease, 71% diabetes, and 86% hypertension). The mean 6MWT distance was 316.2 meters. According to FRIED score, 4.7% were normal and 17.6% were categorized as pre-frail and 77.7% as frail, while according to SOF index 9.8% were normal, 15% were categorized as pre-frail and 75.1% as frail. Frail patients according to both indices had a higher risk of 90-day readmissions, uptitration of diuretics within 90 days (p < 0.001 for both) and numerically but not significantly higher risk of death. Frailty status was independently associated with higher risk of 90-day readmissions, uptitration of diuretics, and higher BNP at 90 days., Conclusions: Frailty in older patients with HF is common and associated with worse prognosis. Pre-discharge frailty assessment may aid in identification of patients at high-risk for short-term complications., (Copyright © 2022 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.)

Aims: Pulmonary artery pressure (PAP)-guided therapy in patients with heart failure (HF) using the CardioMEMS (CMM) device, an implantable PAP sensor, has been shown to reduce HF hospitalizations in previous studies. We sought to evaluate the clinical benefit of the CMM device in regard to 30, 90, and 180 day readmission rates in real-world usage., Methods and Results: We queried the Nationwide Readmissions Database (NRD) to identify patients who underwent CMM implantation (International Classification of Diseases 9 and 10 codes) between the years 2014 and 2019 and studied their HF readmissions. Moreover, we compared CMM patients and their readmissions with a matched cohort of patients with HF but without CMM. Multivariable Cox regression analysis was performed to adjust for other predictors of readmissions. Prior to matching, we identified 5 326 530 weighted HF patients without CMM and 1842 patients with CMM. After propensity score matching for several patients and hospital-related characteristics, the cohort consisted of 1839 patients with CMM and 1924 with HF without CMM. Before matching, CMM patients were younger (67.0 ± 13.5 years vs. 72.3 ± 14.1 years, P < 0.001), more frequently male (62.7% vs. 51.5%, P < 0.001), with higher rates of prior percutaneous coronary intervention (16.9% vs. 13.2%, P = 0.002), peripheral vascular disease (29.6% vs. 17.8%, P < 0.001), pulmonary circulatory disorder (38.7% vs. 23.2%, P < 0.001), atrial fibrillation (51.2% vs. 45.3%, P = 0.002), prior left ventricular assist device (1.8% vs. 0.2%, P < 0.001), high income (32.2% vs. 16.4%, P < 0.001), and acute kidney disease (43.8% vs. 29.9%, P < 0.001). Readmission rates at 30 days were 17.3% vs. 20.9% for patients with vs. without CMM, respectively, and remained statistically significant after matching (17.3% vs. 21.5%, P = 0.002). The rates of 90 day (29.6% vs. 36.5%, P = 0.002) and 180 day (39.6% vs. 46.6%, P = 0.009) readmissions were lower in the CMM group. In a multivariable regression model, CMM was associated with lower risk of readmissions (hazard ratio 0.75, 95% confidence interval 0.63-0.89, P = 0.001)., Conclusions: The CMM device was associated with reduced HF rehospitalization rates in a nationally representative cohort of HF patients, validating the clinical trial that led to the approval of this device and its utilization in the treatment of HF., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Outflow cannula occlusion is an infrequent complication occurring among recipients of continuous flow left ventricular assist devices. Hereby, we present a case of a 66-year-old man with a HeartMate 3 left ventricular assist device that presented 18 months after implantation and during his admission, evidence of poor left ventricular unloading and forward flow uncovered intrinsic and extrinsic outflow cannula obstruction. The patient's course was complicated by cardiogenic shock, diffuse alveolar hemorrhage and multiorgan failure. Post-mortem examination suggested foreign body reaction as a potential contributor of outflow graft obstruction at the level of the bend relief.

Objective: Percutaneous left atrial appendage occlusion (LAAO) is an alternative strategy for prevention of thromboembolic events in patients with atrial fibrillation and unsuitable for long-term oral anticoagulation. The study aimed to evaluate the causes and timing of readmissions within 6 months following percutaneous LAAO in a real-world setting., Methods: We conducted a retrospective cohort study of percutaneous LAAO performed in the USA between January and June of 2016-2018 using the Nationwide Readmissions Database., Results: Overall, 12 446 patients who underwent LAAO were included in the analyses and 3477 patients (28%) were readmitted within 6 months following the interventions. Readmitted patients were more often women (p=0.001). The index hospitalisation was characterised by longer duration of hospital stay (p<0.001) and complicated with acute kidney injury (p<0.001) among readmitted patients compared with those without readmissions. Readmissions within 6 months following the index intervention were mainly due to heart failure (13%) and gastrointestinal bleeding (12%). Characteristics associated with readmissions due to heart failure included previously known heart failure (HR 2.39; 95% CI 1.70 to 3.37), valvular heart disease (HR 1.39; 95% CI 1.05 to 1.84) and chronic kidney disease (HR 1.42; 95% CI 1.03 to 1.94). Readmissions due to gastrointestinal bleeding were associated with diabetes mellitus (HR 1.78; 95% CI 1.25 to 2.53), chronic kidney disease (HR 1.86; 95% CI 1.23 to 2.81) and previous anaemia (HR 2.41; 95% CI 1.54 to 3.77)., Conclusions: After percutaneous LAAO, over a quarter of the patients in the USA required rehospitalisation within 6 months, mainly due to heart failure and gastrointestinal bleeding., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Data regarding the role of N-terminal Pro-B-type natriuretic peptide (NT-pro BNP) in patients with a continuous-flow left ventricular assist device (CFLVAD) is scarce. To evaluate the prognostic implications of measuring both absolute values and changes in NT-pro BNP concentrations in ambulatory patients with a CFLVAD, we performed a retrospective study of 168 consecutive patients who had an LVAD implantation at our institution and survived beyond their index hospitalization. Of these, 127 patients (56.2 ± 12.5 years, 21.2% female) had NT-pro BNP measured at 1 and 3 months postdischarge in ambulatory settings. Compared to the NT-pro BNP concentration at 1 month, 94 patients (74%) had a decline, and 33 patients (26%) had an increase in concentrations, from their 1 month baseline. After a median follow-up of 17 months, a total of 53 (41.7%) adverse events occurred. Of these, 37 (69.8%) were heart failure (HF) hospitalizations, and 16 (30.2%) were deaths. For each 1,000 unit increase in NT-pro BNP concentration at 3 months, there was a 17% increase in the risk of HF hospitalization or death (hazard ratio [HR] = 1.17, 95% confidence interval [CI] = 1.04-1.32, p = 0.007). Conversely, each 1000 unit decline during the same time, was associated with an 11% decrease in the risk of HF hospitalization or death (HR = 0.89, 95% CI = 0.77-0.98, p = 0.04). In conclusion, in patients with a CFLAD, an increase in NT-pro BNP concentration from 1 to 3 months is associated with an increased risk of HF hospitalization and death. In contrast, a decline is associated with a reduction in the risk of HF hospitalization and death., Competing Interests: Disclosures: The authors have no conflicts of interest to report., (Copyright © ASAIO 2021.)

Background: We investigated the current trends and outcomes of diabetic patients listed for heart transplants in the U.S. and provided a method for risk-stratification., Methods: Using data from the United Network for Organ Sharing (UNOS), we identified heart failure patients listed for heart transplants between 2010 and 2019. Diabetic patients were propensity-matched with non-diabetics, and waitlist mortality as well as post-transplant graft survival were compared between the two groups. Further risk-stratification of diabetic patients was done based on the risk factors that independently predict graft failure., Results: 28,928 adult patients (30% diabetic) with end-stage heart failure were added to the waitlist over the study period. In the propensity-matched cohort, waitlist mortality was higher in diabetic patients compared to non-diabetics (HR = 1.13 (95% CI = 1.04-1.22, P = .002). Over the study period, 5739 patients with diabetes were transplanted. In the propensity-matched cohorts of transplant recipients, the rate of graft failure was significantly higher for diabetic patients (23.3%) compared to non-diabetics (20.4%); HR = 1.17, 95% CI = 1.08-1.26, P < .001. We identified 12 risk factors of graft failure among diabetic patients and developed a risk score that further risk-stratify these patients. Diabetic patients at low risk (score≤4) had similar graft survival as patients without diabetes (HR = .91, 95% CI = .82-1.01, P = .06). On the other hand, high-risk diabetic patients had worse graft survival compared to non-diabetics (HR = 1.52, 95% CI = 1.38-1.67, P < .001)., Conclusion: Among patients with end-stage heart failure, pre-existing diabetes was associated with higher waitlist mortality and worse graft survival. However, with careful patient selection, graft survival is similar to those without diabetes., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The utilization and clinical impact of beta-blockers (BBs) in cardiac amyloidosis (CA) is largely unexplored., Methods: We conducted a retrospective, single-center analysis of indications, timing of initiation, types and doses of BB used, reasons to discontinue BB and association between BB tolerance and outcomes in a cohort of patients with immunoglobulin light chain amyloidosis (AL)., Results: We reviewed 236 patients with AL CA and identified 53 patients taking BB (22.5%). Most patients presented in New York Heart Association Class (NYHA) II or III (74.5%) and 24% presented in Mayo stage IIIB. The most frequent indications for BB initiation were atrial fibrillation (AF) and coronary artery disease (CAD). In most cases (59%) BB was started before the diagnosis of CA. The median duration of BB treatment was 9 months (interquartile range [IQR] 3-24 months). Among patients receiving BB, 28 tolerated BB during follow-up whereas 25 patients discontinued BB. The main causes of BB discontinuation were hypotension and heart failure (HF) exacerbation. Patients intolerant to BB presented with more advanced NYHA class, worse performance status and lower median left ventricular ejection fraction (LVEF) at baseline. At median follow-up duration of 17.7 months, patients who did not tolerate BB had a poor survival., Conclusions: Although some patients with CA may have indications for treatment with BB, their use is uncommon and those with more advanced disease tolerate BB poorly. Intolerance to BB in patients with cardiac AL is an indicator of poorer outcome.

Despite decreasing morbidity and mortality in left ventricular assist device (LVAD) recipients, readmission after implantation remains a major problem. Our aim was to investigate the trends and outcomes of 90 and 180 day readmission in this population. The National Readmission Database from 2012 to 2017 was queried to identify LVAD recipients. A total of 5,907 adults (90 day readmissions) and 3,653 adults (180 day readmissions) who survived LVAD implantation during the index admission were included in our analysis. Readmissions occurred in 45.6% and 65.1% by 90 and 180 days, respectively, with most readmissions occurring within the first 20 days. During the study period, mortality at index admission and readmission rate after discharge from index admission remained stable, whereas mortality during the readmission declined overtime both at 90 and 180 days. Heart failure was the most common cause for readmission (both 90 and 180 days), while its incidence also increased over the years. Among the reasons for readmission, intracranial bleeding, ischemic stroke, and device thrombosis were associated with highest mortality and gastrointestinal bleeding with the lowest. Intracranial bleeding, device thrombosis, and device infection were associated with longer length of stay. Multivariate logistic regression models identified gastrointestinal bleeding, length of stay during index admission, and end-stage renal disease requiring hemodialysis as risk factors of readmissions. Our study has unveiled several important factors associated with readmission and mortality. Approaches to identify and prevent readmissions early after LVAD implantation by addressing these factors may lead to lower morbidity, healthcare cost related to readmission, and improved quality of life., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2021.)

Heart failure with reduced ejection fraction (HFrEF) is an increasing global pandemic affecting more than 30 million individuals worldwide. Importantly, HFrEF is frequently accompanied by the presence of cardiac and non-cardiac comorbidities that may greatly influence the management and prognosis of the disease. In this review article, we will focus on three important comorbidities in HFrEF; atrial fibrillation (AF), advanced renal disease, and elderly, which all have a paramount impact on progression of the disease, management strategies, and response to therapy. AF is very common in HFrEF and shares many risk factors. AF aggravates heart failure and contributes to HF-related adverse clinical outcomes; hence it requires special consideration in HFrEF management. The kidney function is largely affected by the reduced cardiac output developed in the setting of HFrEF, and the neurohormonal feedback effects create a complex interplay that pose challenges in the management of HFrEF when renal function is significantly impaired. Cardiorenal syndrome is a challenging sequela with increased morbidity and mortality thereby reflecting the delicate and complex balance between the heart and the kidney in HFrEF and renal failure conditions. Furthermore, patients with advanced renal failure have poor prognosis in the presence of HFrEF with limited treatment options. Finally, aging and frailty are important factors that influence treatment strategies in HFrEF with greater emphasis on tolerability and safety of the various HFrEF therapies in elderly individuals., Competing Interests: The authors declare no conflict of interest. Alexandros Briasoulis is serving as one of the Guest editors of this journal. We declare that Alexandros Briasoulis had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Matteo Cameli and Alberto Palazzuoli., (© 2022 The Author(s). Published by IMR Press.)

The impact of right ventricular impairment (RVI) on the morbidity and mortality of patients with Takotsubo syndrome (TTS) is well-debated. We conducted a meta-analysis to evaluate the mortality and morbidity risk associated with RVI compared with those without RVI in patients with TTS. A comprehensive search was performed in PubMed and Embase from inception to April 19, 2019. Our primary outcome of interest was in-hospital and long-term mortality. Other outcomes of interest were acute heart failure, left ventricular systolic function, tricuspid and mitral regurgitation, and length of hospital stay (LOS). We are reporting our outcomes as a cumulative odds ratio (OR). After an initial search, 10 studies with 1210 subjects were included in the quantitative analysis. Mean follow-up was 31 months. The odds of in-hospital and long-term mortality in TTS patients with and without RVI were not significantly different (p = 0.13 and 0.40). In TTS patients without RVI, the odds of acute heart failure, and mitral and tricuspid regurgitation were significantly lower at an OR of 0.26 (p < 0.0001), 0.40 (p = 0.0001), and 0.52 (p = 0.02) respectively. TTS patients with RVI had significantly lower mean LVEF (34% vs 41%, p = 0.03) and numerically higher mean LOS (9.5 days vs 7.6 days, p = 0.52) compared with those without RVI. The presence of RVI represents a severe form of TTS disease spectrum, characterized by severely reduced LVEF, higher incidence of MR and presence of TR. Although there was a trend toward increased in-hospital and long-term mortality, RVI in TTS does not portend worse survival., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: We sought to investigate temporal trends in patient characteristics, waitlist, and posttransplant outcomes after heart transplantation in the United States., Methods: Using data from the United Network of Organ Sharing, we identified adults listed for heart transplantation between 1991 and 2019. Patients were divided into 4 eras based on the 3 time points in which changes were made to the patient selection/allocation policy (Era 1=January 1991-January 1999; Era 2=January 1999-July 2006; Era 3=July 2006-October 2018; and Era 4=October 2018-March 2020), and patient characteristics, waitlist, and posttransplant outcomes were evaluated for each era., Results: Between 1991 and 2019, 95 179 patients were added to the heart transplantation waitlist. Compared with Era 1, patients listed in Era 4 were older (mean age: 50 versus 52 years) and with higher risk comorbidities (eg, 10% versus 28.8% diabetes, 23.3% versus 35.6% obese). Over the study period, 22 738 patients died or were permanently delisted for deterioration on the waitlist while 61 687 were transplanted. Compared with the preceding era, there was significant decrease in death or deterioration in the last 2 eras (sub-hazard ratio, 0.67 [95% CI, 0.65-0.70] for Era 3 versus Era 2 and sub-hazard ratio, 0.65 [95% CI, 0.58-0.73] for Era 4 versus 3). Across the years, 27.1% to 40.5% of those on the waitlist were transplanted. Among those transplanted, there was increase in the rates of in-hospital stroke (2.8% in Era 1 to 3.7% in Era 4), renal failure requiring dialysis (7.2%-17.1%), and length-of-stay (14-17days), P <0.001. However, this did not negatively impact short-term survival when compared with the preceding era (1-year graft survival from Era 1 to Era 4=84.1%, 86.4%, 90.4%, and 89.7%, respectively)., Conclusions: There have been significant changes in the characteristics of patients listed for heart transplantation. Although transplant volume has increased, the wide supply-demand gap persisted. The last two changes in the allocation policy achieved their primary objective of reducing waitlist mortality.

Background: Post-operative stroke increases morbidity and mortality after cardiac surgery. Data on characteristics and outcomes of stroke after heart transplantation (HTx) are limited., Methods and Results: We conducted a retrospective analysis of the United Network for Organ Sharing (UNOS) database from 2009 to 2020 to identify adults who developed stroke after orthotropic HTx. Heart transplant recipients were divided according to the presence or absence of post-operative stroke. The primary endpoint was all-cause mortality. A total of 25 015 HT recipients were analysed, including 719 (2.9%) patients who suffered a post-operative stroke. The stroke rates increased from 2.1% in 2009 to 3.7% in 2019, and the risk of stroke was higher after the implantation of the new allocation system [odds ratio 1.29, 95% confidence intervals (CI) 1.06-1.56, P = 0.01]. HTx recipients with post-operative stroke were older (P = 0.008), with higher rates of prior cerebrovascular accident (CVA) (P = 0.004), prior cardiac surgery (P < 0.001), longer waitlist time (P = 0.04), higher rates of extracorporeal membrane oxygenation (ECMO) support (P < 0.001), left ventricular assist devices (LVADs) (P < 0.001), mechanical ventilation (P = 0.003), and longer ischaemic time (P < 0.001). After multivariable adjustment for recipient and donor characteristics, age, prior cardiac surgery, CVA, support with LVAD, ECMO, ischaemic time, and mechanical ventilation at the time of HTx were independent predictors of post-operative stroke. Stroke was associated with increased risk of 30 day and all-cause mortality (hazard ratio 1.49, 95% CI 1.12-1.99, P = 0.007)., Conclusions: Post-operative stroke after HTx is infrequent but associated with higher mortality. Redo sternotomy, LVAD, and ECMO support at HTx are among the risk factors identified., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Obesity is a risk factor for heart failure (HF), but its presence among HF patients may be associated with favorable outcomes. We investigated the long-term outcomes across different body mass index (BMI) groups, after cardiac resynchronization therapy (CRT), and whether defibrillator back-up (CRT-D) confers survival benefit. One thousand two-hundred seventy-seven (1,277) consecutive patients (mean age: 67.0 ± 12.7 years, 44.1% women, and mean BMI: 28.3 ± 5.6 Kg/m 2 ) who underwent CRT implantation in 5 centers between 2000-2014 were followed-up for a median period of 4.9 years (IQR 2.4 to 7.5). More than 10% of patients had follow-up for ≥10 years. Patients were classified according to BMI as normal: <25.0 Kg/m 2 , overweight: 25.0 to 29.9 Kg/m 2 and obese: ≥30.0 Kg/m 2 . 364 patients had normal weight, 494 were overweight and 419 were obese. CRT-Ds were implanted in >75% of patients, but were used less frequently in obese individuals. The composite endpoint of all-cause mortality or cardiac transplant/left ventricular assist device (LVAD) occurred in 50.9% of patients. At 10-year follow-up, less than a quarter of patients in the lowest and highest BMI categories were still alive and free from heart transplant/LVAD. After adjustment BMI of 25 to 29.9 Kg/m 2 (HR = 0.73 [95%CI 0.56 to 0.96], p = 0.023) and use of CRT-D (HR = 0.74 [95% CI 0.55 to 0.98], p = 0.039) were independent predictors of survival free from LVAD/heart transplant. BMI of 25 to 29.9 Kg/m 2 at the time of implant was independently associated with favourable long-term 10-year survival. Use of CRT-D was associated with improved survival irrespective of BMI class., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Heart failure (HF) is a complex clinical syndrome characterised by significant morbidity and mortality worldwide. Evidence-based therapies for the management of HF include several well-established neurohormonal antagonists and antiarrhythmic drug therapy to mitigate the onset of cardiac arrhythmia. However, the degree of rate and rhythm control achieved is often suboptimal and mortality rates continue to remain high. Implantable cardioverter-defibrillators (ICDs), cardiac resynchronization (CRT), and combined (CRT-D) therapies have emerged as integral and rapidly expanding technologies in the management of select patients with heart failure with reduced ejection fraction (HFrEF). ICDs treat ventricular arrhythmia and are used as primary prophylaxis for sudden cardiac death, while CRT resynchronizes ventricular contraction to improve left ventricular systolic function. Left ventricular assist device therapy has also been shown to provide clinically meaningful survival benefits in patients with advanced HF, and His-bundle pacing has more recently emerged as a safe, viable, and promising pacing modality for patients with CRT indication. Catheter ablation is another important and well-established strategy for managing cardiac arrhythmia in HF, demonstrating superior efficacy when compared with antiarrhythmic drug therapy alone. In this article, we provide a comprehensive and in-depth evaluation of the role of implantable devices and catheter ablation in patients with HFrEF, outlining current applications, recent advances, and future directions in practice., Competing Interests: The authors declare no conflict of interest., (© 2021 The Author(s). Published by IMR Press.)

In the context of the COVID-19 pandemic, many barriers to telemedicine disappeared. Virtual visits and telemonitoring strategies became routine. Evidence is accumulating regarding the safety and efficacy of virtual visits to replace in-person visits. A structured approach to virtual encounters is recommended. Telemonitoring includes patient reported remote vital sign monitoring, information from wearable devices, cardiac implantable electronic devices and invasive remote hemodynamic monitoring. The intensity of the monitoring should match the risk profile of the patient. Attention to cultural and educational barriers is important to prevent disparities in telehealth implementation., Competing Interests: The authors declare no conflict of interest., (© 2021 The Author(s). Published by IMR Press.)

Background: Heart failure (HF) hospitalizations remains a significant burden on the health care system. Stimulants including cocaine, amphetamine and its derivatives are amongst the most used illegal substances in the United States. The information regarding stimulant-related HF hospitalizations is scarce. We sought to evaluate the characteristics and trends of stimulant-related HF hospitalizations in the United States and their associated outcomes and resource utilization., Methods: Using the National Inpatient Sample (NIS), we identified patients with a primary diagnosis of HF hospitalization. These hospitalizations were further divided into those with and without a concomitant diagnosis of stimulant (cocaine or amphetamine) dependence or abuse. Survey specific techniques were employed to compare trends in baseline characteristics, complications, procedures, outcomes and resource utilization between the two cohorts., Results: We identified 9,932,753 hospitalizations (weighted) with a primary diagnosis of heart failure, of those 138,438 (1.39%) had a diagnosis of active stimulant use. The proportion of stimulant-related HF hospitalization is on the rise (1.1% to 1.9%). Stimulant-related HF hospitalization was highest amongst age group 30-39 years and 7.9% of HF hospitalizations in this age group were due to stimulant use. The proportion of stimulant-related HF hospitalization for the White and Hispanic race has doubled from 2008 to 2017. Stimulant-related HF hospitalization is associated with increased incidence of in-hospital complications like cardiogenic shock, acute kidney injury and ventricular tachycardia. These patients have more than 7-fold higher discharge against medical advice., Conclusions: Stimulant-related HF hospitalizations have been increasing. It is associate with significant morbidity burden and health care utilization., (Copyright © 2021. Published by Elsevier B.V.)

Background: Enhanced platelet reactivity may play a role in cardiac allograft vasculopathy (CAV) progression. The use of antiplatelet agents after heart transplantation (HT) has been inconsistent and although aspirin (ASA) is often a part of the medication regimen after HT, limited evidence is available on its benefit., Methods and Results: CAV progression was assessed by measuring the difference in plaque volume and plaque index between the last follow-up and the baseline coronary intravascular ultrasound examination. Overall, 529 HT recipients were retrospectively analyzed (337 had ≥2 intravascular ultrasound studies). The progression in plaque volume (P = .007) and plaque index (P = .002) was significantly attenuated among patients treated with early ASA (within the first year after HT). Over a 6.7-year follow-up, all-cause mortality was lower with early ASA compared with late or no ASA use (P < .001). No cardiac deaths were observed in the early ASA group, and the risk of CAV-related graft dysfunction was significantly lower in this group (P = .03). However, the composite of all CAV-related events (cardiac death, CAV-related graft dysfunction, or coronary angioplasty) was not significantly different between the groups (P = .16)., Conclusions: Early ASA use after HT may delay CAV progression and decrease mortality and CAV-related graft dysfunction, but does not seem to affect overall CAV-associated events., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Left ventricular assist devices (LVAD) improve morbidity and mortality in end-stage heart failure patients, but high rates of readmissions remain a problem after implantation. We aimed to assess the incidence, trends, outcomes, and predictors of device-related 30-day readmissions after LVAD implantation., Methods: The National Readmission Database was used to identify patients who underwent LVAD implantation between 2012 and 2017 and those with 30-day readmissions., Results: The analysis included a total of 16499 adults who survived the index hospitalization for LVAD implantation. Among those, 28.1% were readmitted at 30 days, and the readmission rate has been grossly stable during the study period. Most of the readmissions occurred in the first 15 days after discharge from the index admission. The most frequent cause of readmissions was gastrointestinal bleeding (14.9% of readmissions), followed by heart failure, arrhythmias, device infection, and device thrombosis. Among reasons for readmission, intracranial bleeding was associated with highest mortality (37.6%), followed by device thrombosis (13.1%), and ischemic stroke (7.6%). Intracranial bleeding and device thrombosis were associated with lengthier stay (20.4 and 15.5 days, respectively). Readmission rates for gastrointestinal bleeding decreased, whereas device infection increased. Multivariate logistic regression model revealed the length of stay, oxygen dependence, gastrointestinal bleeding at index admission, depression and ECMO, private insurance as independent predictors of 30-day readmission., Conclusion: Over one-fourth of LVAD recipients have 30-day readmissions, with most of them occurring within 15 days. Most frequent cause of readmission was gastrointestinal bleeding, which was associated with the lowest in-hospital mortality among other complications., (Copyright © 2020 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background: In PARADIGM-HF, sacubitril/valsartan improved quality of life (QOL) versus enalapril in heart failure with reduced ejection fraction (HFrEF), yet limited data are available regarding QOL changes after sacubitril/valsartan initiation in routine practice., Methods: PROVIDE-HF was a prospective study within a national research network (Patient-Centered Outcomes Research Network) of HFrEF outpatients recently initiated on sacubitril/valsartan versus controls with recent angiotensin-converting enzyme inhibitor/angiotensin receptor blocker initiation/dose change. The primary end point was mean Kansas City Cardiomyopathy Questionnaire (KCCQ) change through 12 weeks. Other end points included responder analyses: ≥5-point and ≥20-point KCCQ increase. Adjusted QOL change was estimated after propensity score weighting., Results: Overall, 270 patients had both baseline and 12-week KCCQ data (151 sacubitril/valsartan; 119 control). The groups had similar demographics and HF details: median EF 28% and N-terminal pro-brain natriuretic peptide 1083 pg/mL. Sacubitril/valsartan patients had larger improvements in KCCQ (mean difference +4.76; P = .027) and were more likely to have a ≥5-point and ≥20-point response (all P < .05). Adjusted comparisons demonstrated similar numerical improvements in the change in KCCQ (+4.55; 95% CI -0.89 to 9.99; P = .101) and likelihood of ≥5-point increase (odds ratio 1.55; 95% CI: 0.84-2.86; P = .16); ≥20-point increase remained statistically significant (odds ratio 3.79; 95% CI 1.47-9.73; P = .006)., Conclusions: In this prospective HFrEF study of sacubitril/valsartan initiation compared with recent angiotensin-converting enzyme inhibitor/angiotensin receptor blocker initiation/dose change, the between-group difference in the primary end point, mean KCCQ change at 12 weeks was not statistically significant following adjustment, but sacubitril/valsartan initiation was associated with early improvements in QOL and a higher likelihood of ≥20-point improvement in KCCQ at 12 weeks. These data add additional real-world evidence related to patient-reported outcomes following the initiation of sacubitril/valsartan in routine clinical practice., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Total artificial heart (TAH) is a viable bridge to transplant (BTT) strategy for patients with severe biventricular failure or complex congenital heart disease. These patients have higher mortality and morbidity than patients undergoing left ventricular assist device (LVAD) implantation. To assess national trends in in-hospital mortality, major complications, cost, length of stay, and disposition of patients undergoing TAH implantation., Methods: Data from the National Inpatient Sample, the largest all-payer inpatient data set in the United States, and the US Census Bureau, for the years 2009 to 2015 were analyzed. Participants included all adult patients who received TAH from 2009 to 2015. Endpoints included in-hospital mortality, in-hospital complications, heart transplantation (HT) in the same admission, length of stay, cost, and disposition at the time of discharge., Results: We identified a total of 143 (weighted = 703) TAH implantations. The number of TAH implants increased during the study period (average annual change +5.8%, p = 0.03). Rates of in-hospital mortality and major complications including ischemic stroke, major bleeding, postoperative infections, acute kidney injury requiring dialysis, and HT did not change significantly over the study period. Although the length of stay and disposition patterns did not change over time, we found a significant increase in cost of hospitalization (average annual change +44,362, p = 0.01). The number of HT during the same hospital stay decreased significantly (average annual change -8.1%, p = 0.02)., Conclusion: In-hospital mortality and complication rates associated with TAH implantation remain increased and did not change in the era of continuous flow LVADs., (Copyright © 2019 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.)

Valvular heart disease is common among left ventricular assist device (LVAD) recipients. However, its management at the time of LVAD implantation remains controversial. Patients who underwent LVAD implantation and concomitant aortic (AVR), mitral (MVR), or tricuspid valve (TVR) repair or replacement from 2010 to 2017 were identified using the national inpatient sample. End points were in-hospital outcomes, length of stay, and cost. Procedure-related complications were identified via ICD-9 and ICD-10 coding and analysis was performed via mixed effect models. A total of 25,171 weighted adults underwent LVAD implantation without valvular surgery, 1,329 had isolated TVR, 1,021 AVR, 377 MVR, and 615 had combined valvular surgery (411 had TVR + AVR, 115 TVR + MVR, 62 AVR + MVR, 25 AVR + MVR + TVR). During the study period, rates of AVR decreased and combined valvular surgeries increased. Patients who underwent TVR or combined valvular surgery had overall higher burden of co-morbidities than LVAD recipients with or without other valvular procedures. Postoperative bleeding was higher with AVR whereas acute kidney injury requiring dialysis was higher with TVR or combined valvular surgery. In-hospital mortality was higher with AVR, MVR, or combined surgery without differences in the rates of stroke. Length of stay did not differ significantly among groups but cost of hospitalization and nonroutine discharge rates were higher for cases of TVR and combined surgery. Approximately 1 in 9 LVAD recipients underwent concomitant valvular surgery and TVR was the most frequently performed procedure. In-hospital mortality and cost were lower among those who did not undergo valvular surgery., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aim: We sought to determine the impact of acute kidney injury (AKI) on in-hospital outcomes in patients presenting with acute heart failure (AHF). Data from National Inpatient Sample (2012- 14) were used to identify patients with the principal diagnosis of AHF and the concomitant secondary diagnosis of AKI., Methods: Propensity score matching was performed on 30 baseline variables to identify a matched cohort. The outcome of interest was in-hospital mortality. We further evaluated in-hospital procedures and complications., Results: Of 1,470,450 patients admitted with AHF, 24.3% had AKI. After propensity matching a matched cohort of 356,940 patients was identified. In this matched group, the AKI group had significantly higher in-hospital mortality (3.8% vs 1.7%, p<0.001). Complications such as sepsis, transfusions and cardiac arrest were also higher in the AKI group (p<0.01). Similarly, in-hospital procedures including pacemaker, coronary artery bypass graft, mechanical ventilation and intra-aortic balloon pump were performed more in the AKI group compared to the non-AKI group. The rate of AKI in patients with AHF has gradually increased from 29 % in the year 2012 to 35% in 2014. AHF patients with AKI had longer in-hospital stay of ~1.7 days., Conclusion: In this propensity score-matched cohort of AHF with and without AKI, the risk of in-hospital mortality was >2-fold in the AKI group. Healthcare utilization and burden of complications were higher in the AKI group., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)