Search

Abstract Aims We aim to identify the most accurate marker for early prediction of poor diuretic response in acute heart failure (AHF) patients with signs of congestion requiring intravenous diuretic treatment. Methods In this single‐centre, prospective observational study, AHF patients with signs of congestion received a standardized intravenous furosemide dose (1 mg/kg of body weight; 40 mg in bolus and remaining dose in 2 h continuous infusion). Subsequently, we assessed spot urine composition at 2 h post‐administration, comparing it with total urine output at 6 h. Various potential urine markers were analysed for predicting urine output using receiver operating characteristic (ROC) curves and logistic regression models. We investigated guideline‐recommended markers, including spot urine sodium (UNa+) and its cut‐off, and introduced the UNa+/UCr (urine creatinine concentration) ratio adjusting UNa+ for urine dilution. Results Out of 111 patients (85% males, 66.4 ± 13.9 years old, NTproBNP 7290 [4493–14 582] pg/ml), there were 18 (16%) with a poor diuretic response (cumulative urine output

Abstract Background Functional health status is increasingly being recognized as a viable endpoint in heart failure (HF) trials. We sought to assess its prognostic impact and relationship with traditional clinical outcomes in patients with HF. Methods MEDLINE and Cochrane central were searched up to January 2021 for post hoc analyses of trials or observational studies that assessed independent association between baseline health/functional status, and mortality and hospitalization in patients with HF across the range of left ventricular ejection fractions to evaluate the prognostic ability of NYHA class [II, III, IV], KCCQ, MLHFQ, and 6MWD. Hazard ratios (HR) with 95% confidence intervals were pooled. Results Twenty-two studies were included. Relative to NYHA I, NYHA class II (HR 1.54 [1.16–2.04]; p 45) was significantly associated with increased mortality (HR 1.30 [1.14–1.47]; p

Abstract In our retrospective study, we aimed to investigate the relationship between urinary chloride (uCl−) and selected clinical and laboratory biomarkers, renal function, and patient outcomes in the acute heart failure (AHF) population. We divided 248 adult patients (≥ 18 years) with AHF into two groups: low uCl− (

BackgroundMuscle wasting is a common finding in critically ill patients associated with increased days of mechanical ventilation in the ICU. Muscle wasting and associated morphological changes are hallmarks of ICU-acquired weakness. Muscle wasting can be diagnosed and quantified by muscle biopsy, but biopsies can cause multiple adverse effects. MuscleSound® has developed a non-invasive, real-time novel MusculoSkeletal (MSK) ultrasound approach to measure the ratio between percentage intramuscular adipose tissue (%IMAT) with muscle cross-section area (MCSA) (termed IMAT-Index). The present study aimed to assess the IMAT-Index in ICU patients longitudinally and compare it to age-matched healthy controls.MethodsTransverse (short-axis) ultrasound images of the rectus femoris muscle were obtained upon admission and discharge in 35 ICU patients and compared to age-matched healthy controls (n = 975). The echo intensity of the image taken from the muscle is used to automatically calculate the ratio between intramuscular adipose tissue by cm2 (IMAT-Index), the cross-sectional area of the muscle (MCSA), and muscle thickness (MT).ResultsIMAT-Index was successfully measured in all subjects. The mean IMAT-index (%IMAT/cm2) upon admission was significantly higher in critically ill patients compared to healthy controls (7.4 ± 4.3 vs. 3.1 ± 0.9, p

IntroductionThe COVID-19 pandemic brought unprecedented challenges to healthcare systems worldwide, particularly the often challenging physical recovery from critical illness. Among the myriad complications faced by these patients, ICU-acquired weakness (ICU-AW) stands out due to its significant impact on patient outcomes. ICU-AW, characterized by skeletal muscle atrophy and weakness, is linked to critical illness polyneuropathy (CIN), myopathy (CIM), and muscle atrophy. Notably, fasciculations, or involuntary muscle twitches, have been observed in patients with ICU-AW, suggesting altered muscle fiber excitability. This study aimed to describe the pattern of fasciculations in critically ill mechanically ventilated COVID-19 patients, assess clinical features associated with fasciculations, and evaluate their prognostic significance.MethodsThe study enrolled patients admitted to the Intensive Care Unit (ICU) with COVID-19 infection requiring intubation and mechanical ventilation. Quadriceps muscles were assessed using muscle skeletal (MSK) ultrasound and Phase Angle (PhA) through multifrequency segmental bioelectrical impedance analysis (MFBIA) every 72 h. PhA is considered a marker of cell membrane integrity and function, with lower PhA values indicating reduced skeletal muscle quality and increased risk of sarcopenia. Fasciculations were classified based on their appearance and frequency.ResultsA total of 35 intubated patients were studied, with 15 patients (43%) displaying scattered fasciculations exclusively in the vastus intermedius muscles. Upon admission, the study found no significant difference in PhA between the fasciculation and non-fasciculation groups. However, PhA decreased significantly from admission to discharge ICU only in the fasciculation group. Patients with fasciculations exhibited higher mortality rates, though not statistically significant, and this correlated with prolonged ICU and hospital lengths of stay.DiscussionThis study is the first to report scattered fasciculations in the vastus intermedius muscles of multiple patients with SARS-CoV-2 infection identified with MSK ultrasound. The findings suggest that the combination of impaired muscle cellular function (PhA) and the onset of fasciculations could serve as a potential biomarker of adverse outcomes and ICU-related muscle dysfunction and muscle loss.

Background Data on the benefits of cardiac resynchronization therapy (CRT) in patients with severe heart failure symptoms are limited. We investigated the relative effects of CRT in patients with ambulatory New York Heart Association (NYHA) IV versus III functional class at the time of device implantation. Methods and Results In this meta‐analysis, we pooled patient‐level data from the MIRACLE (Multicenter InSync Randomized Clinical Evaluation), MIRACLE‐ICD (Multicenter InSync Implantable Cardioversion Defibrillation Randomized Clinical Evaluation), and COMPANION (Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure) trials. Outcomes evaluated were time to the composite end point of the first heart failure hospitalization or all‐cause mortality, and time to all‐cause mortality alone. The association between CRT and outcomes was evaluated using a Bayesian hierarchical Weibull survival regression model. We assessed if this association differed between NYHA III and IV groups by adding an interaction term between CRT and NYHA class as a random effect. A sensitivity analysis was performed by including data from RAFT (Resynchronization‐Defibrillation for Ambulatory Heart Failure). Our pooled analysis included 2309 patients. Overall, CRT was associated with a longer time to heart failure hospitalization or all‐cause mortality (adjusted hazard ratio [aHR], 0.79 [95% credible interval [CI], 0.64–0.99]; posterior probability or P=0.044), with a similar association with time to all‐cause mortality (aHR, 0.78 [95% CI, 0.59–1.03]; P=0.083). Associations of CRT with outcomes were not significantly different for those in NYHA III and IV classes (ratio of aHR, 0.72 [95% CI, 0.30–1.27]; P=0.23 for heart failure hospitalization/mortality; ratio of aHR, 0.70 [95% CI, 0.35–1.34]; P=0.27 for all‐cause mortality alone). The sensitivity analysis, including RAFT data, did not show a significant relative CRT benefit between NYHA III and IV classes. Conclusions Overall, there was no significant difference in the association of CRT with either outcome for patients in NYHA functional class III compared with functional class IV.

Background: Elevated interleukin (IL)-6 levels have been linked to adverse outcomes in patients with and without baseline cardiovascular disease (CVD). Objectives: The purpose of this study was to examine the association between circulating IL-6 levels and CVD events without baseline CVD across racial and ethnic groups. Methods: We conducted an observational analysis utilizing the MESA (Multi-Ethnic Study of Atherosclerosis), a multicenter, prospective community-based study of CVD at baseline from four racial and ethnic groups. IL-6 levels were measured at the time of enrollment (visit 1) and were divided into 3 terciles. Patient baseline characteristics and outcomes, including all-cause mortality, CV mortality, heart failure, and non-CV mortality, were included. Cox proportional hazard regression models were used to assess associations between IL-6 levels and study outcomes with IL-6 tercile 1 as reference. Results: Of 6,622 individuals, over half were women (53%) with a median age of 62 (IQR: 53-70) years. Racial and ethnic composition was non-Hispanic White (39%) followed by African American (27%), Hispanic (22%), and Chinese American (12%). Compared to tercile 1, participants with IL-6 tercile 3 had a higher adjusted risk of and all-cause mortality (HR: 1.98 [95% CI: 1.67-2.36]), CV mortality (HR: 1.55 [95% CI: 1.05-2.30]), non-CV mortality (HR: 2.05 [95% CI: 1.65-2.56]), and heart failure (HR: 1.48 [95% CI: 0.99-2.19]). When tested as a continuous variable, higher levels of IL-6 were associated with an increased risk of all individual outcomes. Compared to non-Hispanic White participants, the unadjusted and adjusted risk of all outcomes across all races and ethnicities was similar across all IL-6 terciles. Conclusions: High levels of circulating IL-6 are associated with worse CV outcomes and increased all-cause mortality consistently across all racial and ethnic groups.

Background: The cardiopulmonary exercise test (CPET) is considered a gold standard in assessing cardiorespiratory fitness (CRF) but has limited accessibility due to competency requirements and cost. Incorporating portable sensor devices into a simple bedside test of CRF could improve diagnostic and prognostic value. Objectives: The authors sought to evaluate the association of an augmented 6-minute incremental step test (6MIST) with standard CPET. Methods: We enrolled patients undergoing clinically indicated supine cycle ergometry CPET with invasive hemodynamics (iCPET) for the same-day 6MIST. CRF-related variables were simultaneously recorded using a signal morphology-based impedance cardiograph (PhysioFlow Enduro) and a portable metabolic analyzer (VO2 Master Pro) during incremental pace stationary stepping. The correlation between CPET and hemodynamic parameters from both tests was assessed using the intraclass correlation coefficient (ICC). Results: Fifteen patients (mean age 60 ± 14 years, 40% female, 27% Black) were included. All patients who agreed to undergo 6MIST completed the study without any test-related adverse events. We observed good to excellent correlation between iCPET- and 6MIST-measured CPET parameters: peak heart rate (ICC = 0.60; 95% CI: 0.15-0.85), absolute peak O2 consumption (VO2) (ICC = 0.77; 95% CI: 0.44-0.92), relative peak VO2 (ICC = 0.64; 95% CI: 0.20-0.86), maximum ventilation (ICC = 0.59; 95% CI: 0.13-0.84), O2 pulse (ICC = 0.71; 95% CI: 0.33-0.89), and cardiorespiratory optimal point (ICC = 0.82; 95% CI: 0.52-0.94). No significant correlation was determined between iCPET and 6MIST in measuring cardiac index at rest (ICC = 0.19; 95% CI: −0.34 to 0.63) or at peak exercise (ICC = 0.36; 95% CI: −0.17 to 0.73). Conclusions: We demonstrate the feasibility of a novel augmented 6MIST with wearable devices for simultaneous CPET and hemodynamic assessment. 6MIST-measured CPET parameters were strongly correlated with the iCPET-derived measurements. Additional studies are needed to confirm the validity of the 6MIST compared to standard upright CPET.

Abstract In this case series, we describe the use of invasive cardiopulmonary exercise testing (iCPET) to diagnose heart failure due to preload reserve failure in two patients with progressive dyspnoea. We demonstrate that underlying liver disease contributes to preload reserve failure as a cause of exertional dysfunction. In liver diseases such as non‐alcoholic fatty liver disease (NAFLD), fibrotic changes to the sinusoidal liver architecture occur leading to an increased transhepatic sinusoidal pressure gradient. Even at the earliest stage of hepatic fibrosis in patients with NAFLD, changes in hepatic blood flow are seen due to outflow block in the sinusoidal area. In this way, changes to the sinusoidal liver architecture can lead to limitations in preload reserve. This case series describes two patients with exertional dyspnoea found to have preload failure on iCPET due to underlying liver disease.

Abstract The decongestion ability in response to diuretic treatment plays a crucial role in the treatment of acute heart failure. This effectiveness is evaluated through the assessment of sodium concentration and urine volume, which are also treatment goals themselves. However, the bidirectional interconnection between these factors remains not fully understood. The objective of this study is to provide mechanistic insights into the correlation between spot urine sodium concentrations (UNa+) and urine dilution. This aims to better understand of the decongestive abilities in acute heart failure (AHF). The study was single-center, prospective, conducted on a group of 50 AHF patients. Each participant received a standardized furosemide dose of 1 mg per kg of body weight. Hourly diuresis was measured in the first 6 h of the study, and urine composition was assessed at predefined timepoints. The study group presented the exponential (rather than linear) pattern of relationship between UNa+ and 6-h urine volume, whereas relationship between eGFR and 6-h urine volume was linear (r = 0.61, p

Abstract Orthostatic hypotension (OH) is common in older people. We examined the influence of self-reported occupational-related physical activity (PA) and leisure-time physical exercise (PE) on orthostatic response in a sample of older people over a 2 year period. Supine and orthostatic systolic blood pressure (sBP), diastolic blood pressure (dBP), and mean blood pressure (mBP) were assessed in response to Active Stand (AS) test in 205 older subjects (> 60 years old) at baseline and 2-year follow-up. OH was found in 24 subjects (11.71%) at baseline and 20 subjects (9.76%) after 2 years, with a significant degree of variability in the occurrence of OH after 2 years. Twenty-two subjects who had OH at baseline were free of it after 2 years, two subjects had persistent OH at baseline and after 2 years. After 2 years, adults with occupational PA showed no significant decrease of blood pressure in response to AS test, while lack of undertaking an occupation-related PA was significantly related with a greater decrease in sBP and mBP in response to AS testing in the 1st min. Occupation-related PA and leisure-time-related PE were related to an increase in the response of BP on AS in change between baseline and after 2 years. High between-subjects variance in OH over 2 years was noted. Occupations that involved continuous physical activity and leisure-time physical exercise in middle age were both protective for BP decline on orthostatic stress test within 2 years.

Abstract At least half of all patients with heart failure (HF) are affected by frailty, a syndrome that limits an individual ability to recover from acute stressors. While frailty affects up to 90% of patients with HF with preserved ejection fraction, it is also seen in ~30–60% of patients with HF with reduced ejection fraction, with ~26% higher prevalence in women compared with men. The relationship between frailty and HF is bidirectional, with both conditions exacerbating the other. Frailty is further complicated by a higher prevalence of sarcopenia (by ~20%) in HF patients compared with patients without HF, which negatively affects outcomes. Several frailty assessment methods have been employed historically including the Fried frailty phenotype and Rockwood Clinical Frailty Scale to classify HF patients based on the severity of frailty; however, a validated HF‐specific frailty assessment tool does not currently exist. Frailty in HF is associated with a poor prognosis with a 1.5‐fold to 2‐fold higher risk of all‐cause death and hospitalizations compared to non‐frail patients. Frailty is also highly prevalent in patients with worsening HF, affecting >50% of patients hospitalized for HF. Such patients with multiple readmissions for decompensated HF have markedly poor outcomes compared to younger, non‐frail cohorts, and it is hypothesized that it may be due to major physical and functional limitations that limit recovery from an acute episode of worsening HF, a care aspect that has not been addressed in HF guidelines. Frail patients are thought to confer less benefit from therapeutic interventions due to an increased risk of perceived harm, resulting in lower adherence to HF interventions, which may worsen outcomes. Multiple studies report that

BackgroundHemodynamic Frontiers in Heart Failure (HF2) is a multicenter academic research consortium comprised of 14 US institutions with mature remote monitoring programs for ambulatory patients with heart failure (HF). The consortium developed a retrospective and prospective registry of patients implanted with a wireless pulmonary artery pressure (PAP) sensor.Goals/aimsHF2 registry collects demographic, clinical, laboratory, echocardiographic (ECHO), and hemodynamic data from patients with PAP sensors. The aims of HF2 are to advance understanding of HF and to accelerate development of novel diagnostic and therapeutic innovations.MethodsHF2 includes adult patients implanted with a PAP sensor as per FDA indications (New York Heart Association (NYHA) Class III HF functional class with a prior hospitalization, or patients with NYHA Class II or brain natriuretic peptide (BNP) elevation without hospitalization) at a HF2 member site between 1/1/19 to present. HF2 registry is maintained at University of Kansas Medical Center (KUMC). The registry was approved by the institutional review board (IRB) at all participating institutions with required data use agreements. Institutions report data into the electronic registry database using REDCap, housed at KUMC.ResultsThis initial data set includes 254 patients implanted from the start of 2019 until May 2023. At time of device implant, the cohort average age is 73 years old, 59.8% are male, 72% have NYHA Class III HF, 40% have left ventricular ejection fraction (LVEF) 50%, mean BNP is 560 pg/ml, mean N-Terminal pro-BNP (NTproBNP) is 5,490 pg/ml, mean creatinine is 1.65 mg/dl. Average baseline hemodynamics at device implant are right atrial pressure (RAP) of 11 mmHg, pulmonary artery systolic pressure (PASP) of 47 mmHg, pulmonary artery diastolic pressure (PADP) 21 mmHg, mean pulmonary artery pressure (mPAP) of 20 mmHg, pulmonary capillary wedge pressure (PCWP) of 19 mmHg, cardiac output (CO) of 5.3 L/min, and cardiac index (CI) of 2.5 L/min/m2.ConclusionA real-world registry of patients implanted with a PAP sensor enables long-term evaluation of hemodynamic and clinic outcomes in highly-phenotyped ambulatory HF patients, and creates a unique opportunity to validate and test novel diagnostic and therapeutic approaches to HF.

Abstract Aims There is considerable variability in the effect of intravenous iron on hard cardiovascular (CV)‐related outcomes in patients with heart failure (HF) in randomized controlled trials (RCTs). We use a meta‐analytic approach to analyse data from existing RCTs to derive a more robust estimate of the effect size of intravenous iron infusion on CV‐related outcomes in patients with HF. Method and results PubMed/Medline was searched using the following terms: (‘intravenous’ and ‘iron’ and ‘heart failure’) from inception till 6 November 2022 for RCTs comparing intravenous iron infusion with placebo or standard of care in patients with HF and iron deficiency. Outcomes were the composite of CV mortality and first hospitalization for HF; all‐cause mortality; CV mortality; first hospitalization for HF; and total hospitalizations for HF. Random effects risk ratio (RR) with 95% confidence intervals (CIs) were calculated. Ten RCTs with a total of 3438 patients were included. Intravenous iron resulted in a significant reduction in the composite of CV mortality and first hospitalization for HF [RR 0.0.85; 95% CI (0.77, 0.95)], first hospitalization for HF [RR 0.82; 95% CI (0.67, 0.99)], and total hospitalizations for HF [RR 0.74; 95% CI (0.60, 0.91)] but no statistically significant difference in all‐cause mortality [RR 0.95; 95% CI. (0.83, 1.09)] or CV mortality [OR 0.89; 95% CI (0.75, 1.05)]. Conclusions Intravenous iron infusion in patients with HF reduces the composite risk of first hospitalization for HF and CV mortality as well as the risks of first and recurrent hospitalizations for HF, with no effect on all‐cause mortality or CV mortality alone.

Abstract Pulmonary arterial pressures are often used as surrogates for intravascular blood volume. However, the relationship between pressure and volume remains controversial. To contextualize and provide concrete examples and impact on clinical management, we report two cases of heart failure (one in heart failure with reduced ejection fraction and one in heart failure with preserved ejection fraction) where pressure‐based measurements did not accurately represent the intravascular status and affected clinical management.

AimsWe sought to conduct a meta-analysis to evaluate the efficacy and safety of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with heart failure (HF) with preserved ejection fraction (HFpEF) and HF with mildly reduced ejection fraction (HFmrEF).MethodsWe searched the Cochrane Library, MEDLINE (via PubMed), Embase, and ClinicalTrials.gov till March 2023 to retrieve all randomized controlled trials of SGLT2i in patients with HFpEF or HFmrEF. Risk ratios (RRs) and standardized mean differences (SMDs) with their 95% confidence intervals (95% CIs) were pooled using a random-effects model.ResultsWe included data from 14 RCTs. SGLT2i reduced the risk of the primary composite endpoint of first HF hospitalization or cardiovascular death (RR 0.81, 95% CI: 0.76, 0.87; I2 = 0%); these results were consistent across the cohorts of HFmrEF and HFpEF patients. There was no significant decrease in the risk of cardiovascular death (RR 0.96, 95% CI: 0.82, 1.13; I2 = 36%) and all-cause mortality (RR 0.97, 95% CI: 0.89, 1.05; I2 = 0%). There was a significant improvement in the quality of life in the SGLT2i group (SMD 0.13, 95% CI: 0.06, 0.20; I2 = 51%).ConclusionThe use of SGLT2i is associated with a lower risk of the primary composite outcome and a higher quality of life among HFpEF/HFmrEF patients. However, further research involving more extended follow-up periods is required to draw a comprehensive conclusion.Systematic Review RegistrationPROSPERO (CRD42022364223).

Abstract Socioeconomic status is an overlooked risk factor for cardiovascular disease (CVD). Low family income is a measure of socioeconomic status and may portend greater CVD risk. Therefore, we assessed the association of family income with cardiovascular risk factor and disease burden in American adults. This retrospective analysis included data from participants aged ≥ 20 years from the National Health and Nutrition Examination Survey (NHANES) cycles between 2005 and 2018. Family income to poverty ratio (PIR) was calculated by dividing family (or individual) income by poverty guidelines specific to the survey year and used as a measure of socioeconomic status. The association of PIR with the presence of cardiovascular risk factors and CVD as well as cardiac mortality and all-cause mortality was examined. We included 35,932 unweighted participants corresponding to 207,073,472 weighted, nationally representative participants. Participants with lower PIR were often female and more likely to belong to race/ethnic minorities (non-Hispanic Black, Mexican American, other Hispanic). In addition, they were less likely to be married/living with a partner, to attain college graduation or higher, or to have health insurance. In adjusted analyses, the prevalence odds of diabetes mellitus, hypertension, coronary artery disease (CAD), congestive heart failure (CHF), and stroke largely decreased in a step-wise manner from highest (≥ 5) to lowest PIR (

Abstract The aim of this research was to examine the prevalence of hyperventilation (defined by pCO2 value) among acute heart failure (AHF) patients and to link it with potential triggers and prognosis. All patients underwent dyspnea severity assessment and capillary blood examination on hospital admission and during hospitalization. Out of 241 AHF patients, 57(24%) were assigned to low pCO2 group (pCO2 ≤ 30 mmHg) and 184 (76%) to normal pCO2 group (pCO2 > 30 mmHg). Low pCO2 group had significantly lower HCO3 - (22.3 ± 3.4 vs 24.7 ± 2.9 mmol/L, p

Abstract Aims Synchronized diaphragmatic stimulation (SDS) modulates intrathoracic and intra‐abdominal pressures with favourable effects on cardiac function for patients with a reduced left ventricular ejection fraction (LVEF) and heart failure (HFrEF). VisONE‐HF is a first‐in‐patient, observational study assessing the feasibility and 1 year effects of a novel, minimally invasive SDS device. Methods and results The SDS system comprises a pulse generator and two laparoscopically delivered, bipolar, active‐fixation leads on the inferior diaphragmatic surface. Fifteen symptomatic men with HFrEF and ischaemic heart disease receiving guideline‐recommended therapy were enrolled (age 60 [56, 67] years, New York Heart Association class II [53%] /III [47%], LVEF 27 [23, 33] %, QRSd 117 [100, 125] ms, & N terminal pro brain natriuretic peptide [NT‐proBNP] 1779 [911, 2,072] pg/mL). Implant success was 100%. Patients were evaluated at 3, 6, and 12 months for device‐related or lead‐related complications, quality of life (SF‐36 QOL), 6 min hall walk distance (6MHWd), and by echocardiography. No implant procedure or SDS‐related adverse event occurred, and patients were unaware of diaphragmatic stimulation. By 12 months, left ventricular end‐systolic volume decreased (136 [123, 170] mL to 98 [89, 106] mL; P = 0.05), 6MHWd increased (315 [300, 330] m to 340 [315, 368] m; P = 0.004), and SF‐36 QOL improved (physical scale 0 [0, 0] to 25 [0, 50], P = 0.006; emotional scale 0 [0, 33] to 33 [33, 67], P = 0.001). Although neither reached statistical significance, LVEF decreased (28 [23, 40]% vs. 34 [29, 38]%; P = ns) and NT‐proBNP was lower (1784 [920, 2540] pg/mL vs. 1492 [879, 2028] pg/mL; P = ns). Conclusions These data demonstrate the feasibility of laparoscopic implantation and delivery of SDS without raising safety concerns. These encouraging findings should be investigated further in adequately powered randomized trials.

Background Splanchnic nerve modulation (SNM) is an emerging procedure to reduce cardiac filling pressures in heart failure. Although the main contributor to reduction in cardiac preload is thought to be increased venous capacitance in the splanchnic circulation, supporting evidence is limited. We examined changes in venous capacitance surrogates pre‐ and post‐SNM. Methods and Results This is a prespecified analysis of a prospective, open‐label, single‐arm interventional study evaluating the effects of percutaneous SNM with ropivacaine in chronic heart failure with elevated filling pressures at rest and with exercise. Patients underwent cardiopulmonary exercise testing with invasive hemodynamic assessment pre‐ and post‐SNM. Blood pressure changes with modified Valsalva maneuver and hemoconcentration, pre‐ and post‐SNM were compared using a repeated measures model. Inferior vena cava diameter and collapsibility (>50% decrease in size with inspiration), and presence of bendopnea pre‐ and post‐SNM were also compared. Fifteen patients undergoing SNM (age 58 years, 47% women, 93% with left ventricular ejection fraction ≤35%) were included. After SNM, changes in systolic blood pressure during Valsalva (peak‐to‐trough) were greater (41 versus 48 mm Hg, P=0.025). Exercise‐induced hemoconcentration was unchanged (0.63 versus 0.43 g/dL, P=0.115). Inferior vena cava diameter was reduced (1.59 versus 1.30 cm, P=0.034) with higher collapsibility (33% versus 73%, P=0.014). Bendopnea was less (47% versus 13%, P=0.025). Conclusions SNM resulted in increased venous capacitance, associated decreased cardiac preload, and decreased bendopnea. Minimally invasive measures of venous capacitance could serve as markers of successful SNM. Long‐term effects of SNM on venous capacitance warrant further investigation for heart failure management. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03453151.

Background Nonalcoholic fatty liver disease (NAFLD) and heart failure with preserved ejection fraction (HFpEF) share common risk factors, including obesity and diabetes. They are also thought to be mechanistically linked. The aim of this study was to define serum metabolites associated with HFpEF in a cohort of patients with biopsy‐proven NAFLD to identify common mechanisms. Methods and Results We performed a retrospective, single‐center study of 89 adult patients with biopsy‐proven NAFLD who had transthoracic echocardiography performed for any indication. Metabolomic analysis was performed on serum using ultrahigh performance liquid and gas chromatography/tandem mass spectrometry. HFpEF was defined as ejection fraction >50% plus at least 1 echocardiographic feature of HFpEF (diastolic dysfunction, abnormal left atrial size) and at least 1 heart failure sign or symptom. We performed generalized linear models to evaluate associations between individual metabolites, NAFLD, and HFpEF. Thirty‐seven out of 89 (41.6%) patients met criteria for HFpEF. A total of 1151 metabolites were detected; 656 were analyzed after exclusion of unnamed metabolites and those with >30% missing values. Fifty‐three metabolites were associated with the presence of HFpEF with unadjusted P value

Recent advances in wearable technology through convenient and cuffless systems will enable continuous, noninvasive monitoring of blood pressure (BP), heart rate, and heart rhythm on both longitudinal 24‐hour measurement scales and high‐frequency beat‐to‐beat BP variability and synchronous heart rate variability and changes in underlying heart rhythm. Clinically, BP variability is classified into 4 main types on the basis of the duration of monitoring time: very‐short‐term (beat to beat), short‐term (within 24 hours), medium‐term (within days), and long‐term (over months and years). BP variability is a strong risk factor for cardiovascular diseases, chronic kidney disease, cognitive decline, and mental illness. The diagnostic and therapeutic value of measuring and controlling BP variability may offer critical targets in addition to lowering mean BP in hypertensive populations.

The relationship between post-recovery COVID-19 and incident heart failure has not been investigated at scale. Here, the authors use electronic health records for ~600,000 patients in the US and find a higher rate of post-discharge incident heart failure in those hospitalised with COVID-19 than without.

Abstract Synchronized diaphragmatic stimulation (SDS) is a novel extra‐cardiac device‐based therapy for symptomatic heart failure with reduced ejection fraction. SDS provides imperceptible chronic stimulation of the diaphragm through a laparoscopically implanted system consisting of an implantable pulse generator and two sensing/stimulating leads affixed to the inferior surface of the diaphragm delivering imperceptible R‐wave gaited pulses that alter intrathoracic pressure improving ventricular filling and cardiac output. We describe, in a man with a history of myocardial infarctions resulting in heart failure and persistent New York Heart Association Class III symptoms despite standard therapies, the successful implantation of SDS resulting in improved quality of life, N‐terminal pro brain natriuretic peptide, cardiac function, and exercise tolerance through 12 months of follow‐up. Randomized trials are now required to validate these findings.

BackgroundIn this multicenter prospective study, we explored the relationship between pulmonary artery pressure (PAP) at rest and in response to a 6-min walk test (6MWT) in ambulatory patients with heart failure (HF) with an implantable PAP sensor (CardioMEMS, Abbott).MethodsBetween 5/2019 and 2/2021, HF patients with a CardioMEMS sensor were recruited from seven sites. PAP was recorded in the supine and seated position at rest and in the seated position immediately post-exercise.ResultsIn our cohort of 66 patients, mean age was 70 ± 12 years, 67% male, left ventricular ejection fraction (LVEF) 15 mmHg) demonstrated a greater increase in post-exercise PAP.ConclusionThe measurement of PAP with CardioMEMS is feasible immediately post-exercise. Despite being well-managed, patients had severely limited functional capacity. We observed a significant increase in PAP with ambulation which was greater in patients with higher baseline pressures.

Abstract Aims Hospitalization for heart failure (HF) constitutes a major healthcare and economic burden. Trends and characteristics of hospitalizations for HF for the recent years are not clear. We sought to determine the trends and characteristics of hospitalization for HF in the United States. Method and results A retrospective analysis of the National Inpatient Sample weighted data between 1 January 2004 and 31 December 2018, which included hospitalized adults ≥ 18 years with primary discharge diagnosis of HF using International Classification of Diseases‐9/10 administrative codes. Main outcomes were trends in hospitalizations for HF (per 1000 person) and inpatient mortality (%) between 2004 and 2018. Conclusions Hospitalizations for HF have been increasing across both sexes and age groups since 2013, whereas inpatient mortality has been decreasing over the study period. Blacks have the highest risk of hospitalization for HF, and Whites have the highest in‐hospital mortality. There are significant racial and geographic disparities related to hospitalizations for HF.

Abstract Background There is uncertainty and limited data regarding initiation of sodium-glucose cotransporter 2 (SGLT2) inhibitors among patients hospitalized with acute heart failure (AHF). This systematic review and meta-analysis aim to establish the efficacy and safety of SGLT2 inhibitors initiated in patients hospitalized for AHF. Methods PubMed/Medline, Embase, and Cochrane library were searched using the following terms: (“sglt2" and "acute heart failure") and (“sglt2" and "worsening heart failure") from inception till November 15th, 2021 for randomized controlled trials (RCTs) comparing the efficacy and safety of initiating an SGLT2 inhibitor compared with placebo in patients with AHF. Major cardiovascular and diabetes scientific meetings in 2021 were also searched for relevant studies. Prespecified efficacy outcomes were all-cause mortality, rehospitalization for heart failure, and improvement in Kansas City Cardiomyopathy Questionnaire (KCCQ) scale score. Prespecified safety outcomes were acute kidney injury (AKI), hypotension, and hypoglycemia. Random effects odds ratio (OR) and mean difference with 95% confidence intervals (CIs) were calculated. Results Three RCTs with a total of 1831 patients were included. Initiation of SGLT2 inhibitors in patients with AHF reduced the risk of rehospitalization for heart failure (OR 0.52; 95% CI [0.42, 0.65]) and improved Kansas City Cardiomyopathy Questionnaire scores (mean difference 4.12; 95% CI [0.1.89, 6.53]). There was no statistically significant effect for initiation of SGLT2 inhibitors in patients with AHF on all-cause mortality (OR 0.70; 95% CI [0.46, 1.08]). Initiation of SGLT2 inhibitors in patients with AHF did not increase the acute kidney injury (OR 0.76; 95% CI [0.50, 1.16]), hypotension (OR 1.17; 95% CI [0.80, 1.71]), or hypoglycemia (OR 1.51; 95% CI [0.86, 2.65]). Conclusion Initiation of SGLT2 inhibitors in patients hospitalized for AHF during hospitalization or early post-discharge (within 3 days) reduces the risk of rehospitalization for heart failure and improves patient-reported outcomes with no excess risk of adverse effects.

Abstract Aims Both left atrial strain (LAS) and skeletal muscle endurance demonstrate a linear relationship to peak VO2. Less is known about the relationship between central (cardiac) and peripheral (muscle endurance) limitations of exercise capacity in patients with heart failure (HF). We investigated this relationship using novel cardiac markers such as LAS and left atrial emptying fraction (LAEF). Methods and results We analysed echocardiographic measurements, cardiopulmonary exercise testing (CPET), and isokinetic muscle function in 55 subjects with HF and controls [17 heart failure with preserved ejection fraction (HFpEF), 18 heart failure with reduced ejection fraction (HFrEF), and 20 healthy controls]. Patients with reduced LAEF showed reduced peak VO2: 14.3 ± 3.5 vs. 18.5 ± 3.5 mL/min/kg, P = 0.003, and reduced muscle endurance (RME): 64.3 ± 23.9 vs. 88.5 ± 32.3 Nm/kg, P = 0.028. Patients with reduced LAS showed similar results. Neither left ventricular global longitudinal strain (LVGLS) nor left atrial volume index (LAVI) was associated with RME. The area under the curve of LAS and LAEF in patients with HF in association with RME were (0.76 vs. 0.80) with 95% confidence interval (CI) (0.59–0.96, P = 0.012 vs. 0.63–0.98, P = 0.006, respectively). In a multiple linear regression, LAEF and working load measured during CPET (watt) were independent factors for RME after adjusting for age, LVGLS, and 6 min walk test (6MWT) [LAEF (B: 0.09, 95% CI: 1.01; 1.18, P = 0.024), working load (B: 0.05, 95% CI: 1.01; 1.08, P = 0.006)]. Peak torque of the left leg was associated with E/LAS (E: early diastolic) in patients with HFpEF (r = −0.6, P = 0.020). Endurance of the left leg was associated with LAEF (r = 0.79, P = 0.001) in patients with HFrEF. Conclusions LAS/LAEF are potential cardiac markers in demonstrating the link between cardiac and peripheral limitations of exercise capacity. Thus, integrating LAS/LAEF in the evaluation of exercise intolerance in patients with HF could be useful.

Abstract Intravascular volume is largely regulated by the kidneys but how differences in intravascular volume profiles interact with chronic kidney disease (CKD) to influence outcomes in chronic heart failure (HF) has not been explored. Our hypothesis was that a greater degree of volume expansion (VE) would moderate the impact of CKD on HF‐related clinical outcomes. Quantitative blood volume (BV) data were available in 137 patients at the time of hospital discharge using a nuclear medicine radiolabeled albumin indicator‐dilution technique. The study patients were stratified by the cohort median glomerular filtration rate (GFR, 44 ml/min/1.73 m2). An a priori cut‐point of ≥+25% above normal BV was then used to further stratify the two GFR subgroups and prospectively analyzed for 1‐year HF‐related mortality or 1st re‐hospitalization. Persistent BV expansions ≥+25% were present in 51% of the cohort. In the subgroup with GFR above the median (N = 68) greater or lesser BV expansion from +25% did not differentiate outcomes. However, in the subgroup with GFR below the median (N = 69), BV expansion‐stratified risk (log‐rank p = 0.022) with

Background: Synchronized diaphragmatic stimulation (SDS) produces localized contractions of the diaphragm gated to the cardiac cycle to transiently modulate intrathoracic pressures, thereby impacting cardiac function for heart failure patients with reduced ejection fraction (HFrEF). This study prospectively evaluated the safety and 1-year effectiveness of SDS in an expanded first-in-patient cohort using multiple implant methods. Methods: Symptomatic patients with HFrEF despite guideline-directed therapy were enrolled. Patients were evaluated at 3, 6 and 12 months for adverse events, quality of life (SF-36 QOL), echocardiography and 6-minute hall walk distance. The SDS system consists of 2 bipolar, active-fixation leads, and an implantable pulse generator. Results: Nineteen men were enrolled (age 63 [57, 67] years, New York Heart Association class II [53%]/III [47%], N-terminal pro B-type natriuretic peptide 1779 [886, 2309] pg/mL, left ventricular ejection fraction 27 [23, 33] %). Three implant techniques (abdominal laparoscopy: sensing and stimulating leads on the inferior diaphragm (n = 15); subxiphoid access for an epicardial sensing lead and abdominal laparoscopy for stimulation on the inferior diaphragm (n = 2); thoracoscopy to place an epicardial sensing lead and a stimulating lead on the superior diaphragm (n = 2)) were employed with 100% success. Patients were unaware of diaphragmatic stimulation. From discharge to 12 months, 6-minute hall walk distance increased (315 [296, 332]m to 340 [319, 384]m; p = 0.002), left ventricular end-systolic volume decreased (135 [114, 140]mL to 99 [90, 105]mL; p = 0.04), and SF-36 QOL improved (physical scale 0 [0, 0] to 25 [0, 50], p = 0.004; emotional scale 0 [0, 33] to 67 [33, 67], p = 0.001). N-terminal pro B-type natriuretic peptide was lower (1784 [944, 2659]pg/mL vs. 962 [671, 1960]pg/mL; p = ns) and left ventricular ejection fraction increased (28 [23, 38]% vs. 35 [31, 40]%; p = ns) although neither reached statistical significance. There were no procedure- or SDS-related adverse events. Conclusions: These data demonstrate that SDS can be delivered using alternative implantation methods without raising safety concerns and suggest improved outcomes over 1 ​year of follow-up. Adequately powered randomized trials are now needed to confirm these findings.

Abstract Heart failure (HF) does not occur in a vacuum and is commonly defined and exacerbated by its co‐morbid conditions. Neurohormonal imbalance and systemic inflammation are some of the key pathomechanisms of HF but also commonly encountered co‐morbidities such as arterial hypertension, diabetes mellitus, cachexia, obesity and sleep‐disordered breathing. A cornerstone of HF management is neurohormonal blockade, which in HF with reduced ejection fraction has been tied to a reduction in morbidity and mortality. Pharmacological treatment effective in patients with HF with reduced ejection fraction did not show substantial effects in HF with preserved ejection fraction. Here, we review novel device‐based therapies using neuromodulation of extra‐cardiac targets to treat cardiometabolic disease.

Abstract Aims Associations between growth differentiation factor‐15 (GDF‐15), cardiovascular outcomes, and exercise capacity among patients with a recent hospitalization for heart failure (HHF) and heart failure with reduced ejection fraction (HFrEF) are unknown. We utilized data from the ‘Functional Impact of GLP‐1 for Heart Failure Treatment’ (FIGHT) study to address these knowledge gaps. Methods and results FIGHT was a randomized clinical trial testing the effect of liraglutide (vs. placebo) among 300 participants with HFrEF and a recent HHF. Multivariable regression models evaluated associations between baseline GDF‐15 and change in GDF‐15 (per 1000 pg/mL increase from baseline to 30 days) with clinical outcomes (at 180 days) and declines in exercise capacity (6 min walk distance ≥ 45 m). At baseline (n = 249), median GDF‐15 value was 3221 pg/mL (interquartile range 1938–5511 pg/mL). Participants in the highest tertile of baseline GDF‐15 were more likely to be male and have more co‐morbidities. After adjustment, an increase in GDF‐15 over 30 days was associated with higher risk of death or HHF [hazard ratio 1.35, 95% confidence interval (CI) 1.11–1.64]. In addition, higher baseline GDF‐15 (per 1000 pg/mL until 6000 pg/mL) and an increase in GDF‐15 over 30 days were associated with declining 6 min walk distance (odds ratio 1.26, 95% CI 1.02–1.55 and odds ratio 1.37, 95% CI 1.12–1.69, respectively). GDF‐15 levels remained stable among participants randomized to liraglutide. Conclusions An increase in GDF‐15 over 30 days among patients in HFrEF was independently associated with an increased risk of cardiovascular events and declining exercise capacity. These results support the value of longitudinal GDF‐15 trajectory in informing risk of heart failure disease progression.

Abstract Aims Most studies examined spot urine sodium's (sUNa+) prognostic utility during the early phase of acute heart failure (AHF) hospitalization. In AHF, sodium excretion is related to clinical status; therefore, we investigated the differences in the prognostic information of spot UNa+ throughout the course of hospitalization for AHF (admission vs. discharge). Methods and results The study population were AHF patients (n = 172), who survived the index hospitalization. We compared the relationship between early (on admission, at 24 and 48 h) and discharge sUNa+ measurements with post‐discharge study endpoints: composite of 1 year all‐cause mortality and AHF rehospitalization (with time to first event analysis) as well as with each event in separation. There were 49 (28.5%) deaths, 40 (23.3%) AHF rehospitalizations, while the composite endpoint occurred in 69 (40.1%) during 1 year follow‐up. The sUNa+ had prognostic significance for the composite endpoint when assessed on admission, at 24 and at 48 h: hazard ratios (HRs) with 95% confidence intervals (CIs) (per 10 mmol/L) were 0.88 (0.82–0.94); 0.87 (0.81–0.91); 0.90 (0.84–0.96), all P

Since the outbreak of the COVID-19 pandemic, races across academia and industry have been initiated to identify and develop disease modifying or preventative therapeutic strategies has been initiated. The primary focus has been on pharmacological treatment of the immune and respiratory system and the development of a vaccine. The hyperinflammatory state (“cytokine storm”) observed in many cases of COVID-19 indicates a prognostically negative disease progression that may lead to respiratory distress, multiple organ failure, shock, and death. Many critically ill patients continue to be at risk for significant, long-lasting morbidity or mortality. The human immune and respiratory systems are heavily regulated by the central nervous system, and intervention in the signaling of these neural pathways may permit targeted therapeutic control of excessive inflammation and pulmonary bronchoconstriction. Several technologies, both invasive and non-invasive, are available and approved for clinical use, but have not been extensively studied in treatment of the cytokine storm in COVID-19 patients. This manuscript provides an overview of the role of the nervous system in inflammation and respiration, the current understanding of neuromodulatory techniques from preclinical and clinical studies and provides a rationale for testing non-invasive neuromodulation to modulate acute systemic inflammation and respiratory dysfunction caused by SARS-CoV-2 and potentially other pathogens. The authors of this manuscript have co-founded the International Consortium on Neuromodulation for COVID-19 to advocate for and support studies of these technologies in the current coronavirus pandemic.

Background Clinical prediction models have been developed for hospitalization for heart failure in type 2 diabetes. However, a systematic evaluation of these models’ performance, applicability, and clinical impact is absent. Methods and Results We searched Embase, MEDLINE, Web of Science, Google Scholar, and Tufts’ clinical prediction registry through February 2021. Studies needed to report the development, validation, clinical impact, or update of a prediction model for hospitalization for heart failure in type 2 diabetes with measures of model performance and sufficient information for clinical use. Model assessment was done with the Prediction Model Risk of Bias Assessment Tool, and meta‐analyses of model discrimination were performed. We included 15 model development and 3 external validation studies with data from 999 167 people with type 2 diabetes. Of the 15 models, 6 had undergone external validation and only 1 had low concern for risk of bias and applicability (Risk Equations for Complications of Type 2 Diabetes). Seven models were presented in a clinically useful manner (eg, risk score, online calculator) and 2 models were classified as the most suitable for clinical use based on study design, external validity, and point‐of‐care usability. These were Risk Equations for Complications of Type 2 Diabetes (meta‐analyzed c‐statistic, 0.76) and the Thrombolysis in Myocardial Infarction Risk Score for Heart Failure in Diabetes (meta‐analyzed c‐statistic, 0.78), which was the simplest model with only 5 variables. No studies reported clinical impact. Conclusions Most prediction models for hospitalization for heart failure in patients with type 2 diabetes have potential concerns with risk of bias or applicability, and uncertain external validity and clinical impact. Future research is needed to address these knowledge gaps.

Abstract Aims Non‐alcoholic fatty liver disease leads to progressive liver fibrosis and appears to be a frequent co‐morbid disease in heart failure with preserved ejection fraction (HFpEF). It is well known that liver fibrosis severity predicts future liver‐related morbidity and mortality, but its impact on outcomes in patients with HFpEF remains unknown. This analysis aimed to describe the prevalence of liver fibrosis, as assessed using surrogate biomarkers, in patients with HFpEF and the association of such biomarkers in predicting clinical outcomes in these patients. Methods and results Patients with HFpEF from TOPCAT Americas were included in the analysis. The non‐alcoholic fatty liver disease fibrosis score (NFS) and fibrosis‐4 (FIB‐4) scores were calculated using a combination of clinical characteristics and laboratory parameters. Risk of advanced fibrosis was classified as low, intermediate, and high. For the 1423 with sufficient data, we used Cox regression analysis to test the association between the risk of fibrosis severity and the combined primary endpoint of all cardiovascular death, aborted cardiac arrest, and hospitalization for heart failure. Advanced fibrosis, as determined by high fibrosis scores, was present in 37.57% by the NFS and 8.02% by the FIB‐4. Higher risk of advanced hepatic fibrosis was associated with older age. In unadjusted models, the risk of advanced fibrosis was associated with the primary cardiovascular outcome [NFS high vs. low, hazard ratio (HR) 1.709 (95% confidence interval, CI 1.238–2.358, P = 0.0011) and FIB‐4 high vs. low, HR 1.561 (95% CI 1.139–2.140, P = 0.0056)]. After multivariable adjustment, this association was diminished [NFS high vs. low, HR 1.349 (95% CI 0.938–1.939, P = 0.1064) and FIB‐4 high vs. low, HR 1.415 (95% CI 0.995–2.010, P = 0.0531)]. Conclusions Our study suggests that advanced liver fibrosis, as estimated by fibrosis risk scores, may not be uncommon in patients with HFpEF, and there appears to be a limited independent association between liver fibrosis risk scores and clinical outcomes related to heart failure events.

Abstract Aims Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous condition, and tissue congestion manifested by oedema is not present in all patients. We compared clinical characteristics, exercise capacity, and outcomes in patients with HFpEF with and without oedema. Methods and results This study was a post hoc analysis of pooled data of patients with left ventricular ejection fraction of ≥50% enrolled in the DOSE, CARRESS‐HF, RELAX, ATHENA, ROSE, INDIE, and NEAT trials. Patients were dichotomized by the severity of oedema. Cox proportional hazard regression and generalized linear regression models were used to assess associations between oedema, symptoms, and clinical outcomes. The ambulatory cohort included 393 patients (228 with and 165 without oedema), and the hospitalized cohort included 338 patients (249 with ≥moderate oedema and 89 with mild or none). Among ambulatory patients, patients with oedema had a higher body mass index (35.2 kg/m2 [inter‐quartile range, IQR 30.5, 41.6] vs. 31.6 kg/m2 [IQR 27.9, 36.3], P

In the COVID-19 era, the heart failure community has witnessed an unprecedented reduction in heart failure–related patient visits and hospitalizations. Social distancing measures present a dilemma for patients with heart failure who require frequent surveillance of volume status and vital signs to minimize heart failure–related symptoms and hospitalizations. With the rise of telemedicine comes an increased focus on remote monitoring technologies. This report describes use of a multisensor device algorithm in implantable cardioverter defibrillator devices by Boston Scientific, called HeartLogic. We present 2 cases of patients with advanced heart failure who were actively surveilled by the HeartLogic device algorithm to guide care. (Level of Difficulty: Beginner.)

Objective: To describe the intent and early outcomes of elective inotrope use during heart failure hospitalization. Patients and Methods: A prospective multisite design was used to collect data for hemodynamically stable patients started electively on inotrope therapy between January 1 and August 31, 2018. We prospectively recorded data when intravenous inotropic therapy was initiated, including survey of the attending cardiologists regarding expectations for the clinical course. Patients were followed up for events through hospital discharge and an additional survey was administered at the end of hospitalization. Results: For the 92 patients enrolled, average age was 60 years and ejection fraction was 24%±12%. At the time of inotrope initiation, attending heart failure cardiologists predicted that 50% (n=46) of the patients had a “high or very high” likelihood of becoming dependent on intravenous inotropic therapy and 58% (n=53) had a “high” likelihood of death, transplant, or durable ventricular assist device placement within the next 6 months. Provider predictions regarding death/hospice or need for continued home infusions were accurate only 51% (47 of 92) of the time. Only half the patients (n=47) had goals-of-care conversations before inotrope treatment initiation. Conclusion: More than half the patients (51 of 92) electively started on inotrope treatment without present or imminent cardiogenic shock ultimately required home inotrope therapy, died during admission, or were discharged with hospice. Heart failure clinicians could not reliably identify those patients at the time of inotrope therapy initiation and goals-of-care discussions were not frequently performed.

Abstract Currently, the assessment of left ventricular ejection fraction (LVEF) is the cornerstone of the classification of patients with heart failure (HF). The mid‐range LVEF (HFmrEF) category was identified in an attempt to uncover specific characteristics of these patients. So far, the analysis of trials, registries, and observational studies have demonstrated that patients with mid‐range LVEF belong to a patient cohort with generally intermediate clinical profile as compared with other groups but with a remarkable variety of intrinsic phenotypes. This is due to the limitations of LVEF as the sole criterion to categorize patients with HF and characterize their prognosis, above all when it is >40%. To better define the HFmrEF phenotype, it is reasonable to consider other parameters, such as LVEF changes over time, HF aetiology, co‐morbidities, and other imaging parameters. A multiparametric evaluation may contextualize a patient with HFmrEF in a more defined phenotype with a specific prognosis.

A 77-year-old man with history of ischemic cardiomyopathy and left ventricular assist device (LVAD) presented with abdominal pain after a lawn mower accident. Examination and imaging revealed a displaced LVAD driveline and a pericardial hematoma secondary to traumatic coronary artery injury. The patient was treated with coronary artery coil embolization. (Level of Difficulty: Advanced.)

We describe a case of inherited restrictive cardiomyopathy in a patient presenting with severe biatrial enlargement. We review the evaluation and management of restrictive cardiomyopathy with a focus on genetic etiologies. (Level of Difficulty: Intermediate.)

Background Nonalcoholic fatty liver disease (NAFLD) and heart failure (HF) are increasing in prevalence. The independent association between NAFLD and downstream risk of HF and HF subtypes (HF with preserved ejection fraction and HF with reduced ejection fraction) is not well established. Methods and Results This was a retrospective, cohort study among Medicare beneficiaries. We selected Medicare beneficiaries without known prior diagnosis of HF. NAFLD was defined using presence of 1 inpatient or 2 outpatient claims using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD‐9‐CM), claims codes. Incident HF was defined using at least 1 inpatient or at least 2 outpatient HF claims during the follow‐up period (October 2015–December 2016). Among 870 535 Medicare patients, 3.2% (N=27 919) had a clinical diagnosis of NAFLD. Patients with NAFLD were more commonly women, were less commonly Black patients, and had a higher burden of comorbidities, such as diabetes, obesity, and kidney disease. Over a mean 14.3 months of follow‐up, patients with (versus without) baseline NAFLD had a significantly higher risk of new‐onset HF in unadjusted (6.4% versus 5.0%; P