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• In those with cardiac amyloidosis and heart failure-related cardiogenic shock, there was significant augmentation of cardiac index after intra-aortic balloon pump (IABP) and significant decreases in left ventricular and right ventricular filling pressures. • Predictors of lack of response to IABP by cardiac index were a smaller baseline left ventricular end-diastolic diameter size per centimeter and higher pre-IABP systemic vascular resistance. • Most patients with Society for Cardiovascular Angiography and Interventions stage C heart failure-related cardiogenic shock were stabilized successfully and bridged to advanced therapies with IABP alone. In those with heart failure-related cardiogenic shock (HF-CS), an intra-aortic balloon pump (IABP) may improve hemodynamics and be useful as a bridge to advanced therapies. We explore whether those with cardiac amyloidosis and HF-CS might experience hemodynamic improvement and describe the hemodynamic response after IABP. We retrospectively identified consecutive patients with a diagnosis of cardiac amyloid, either light chain or transthyretin, who were admitted to our intensive care unit with HF-CS. Patients were excluded if an IABP was placed during heart transplant or for shock related to acute myocardial infarction. Invasive hemodynamics before and after IABP placement were assessed. We identified 23 patients with cardiac amyloid who had an IABP placed for HF-CS. The 1-year survival rate was 74% and most (65%) were bridged to heart transplant, although 1 patient was bridged to destination left ventricular assist device. After IABP, the mean arterial pressure, cardiac index, and cardiac power index were significantly increased, whereas mean right atrial pressure, mean pulmonary artery pressure, and pulmonary capillary wedge pressure were all significantly decreased. A smaller left ventricular end-diastolic diameter (per cm) was associated with a higher likelihood of a cardiac index of <2.2 L/min/m2 after IABP (odds ratio 0.16, 95% confidence interval 0.01–0.93, P =.04). IABP significantly improved cardiac index while decreasing right atrial pressure, mean pulmonary artery pressure, and pulmonary capillary wedge pressure in cardiac amyloidosis patients with HF-CS. [Display omitted] [ABSTRACT FROM AUTHOR]

Evidence for modulating the sodium chloride (NaCl) intake of patients hospitalized with acute heart failure (AHF) is inconclusive. Salt restriction may not benefit; hypertonic saline may aid diuresis. To compare the safety and efficacy of oral NaCl during intravenous (IV) diuretic therapy in renal function and weight. Seventy hospitalized patients with AHF who were being treated with IV furosemide infusion consented to receive, randomly, 2 grams of oral NaCl or placebo 3 times a day in a double-blind manner during diuresis. Treatment efficacy (bivariate primary endpoints of change in serum creatinine levels and change in weight) was measured at 96 hours, and adverse safety events were tracked for 90 days. Sixty-five patients (34 NaCl, 31 placebo) were included for analysis after 5 withdrew. A median of 13 grams of NaCl was given compared to placebo. At 96 hours, there was no significant difference between treatment groups with respect to the primary endpoint (P = 0.33); however, the trial was underpowered, and there was greater than expected standard deviation in weight change. The mean change in creatinine levels and weight was 0.15 ± 0.44 mg/dL and 4.6 ± 4.2 kg in the placebo group compared with 0.04 ± 0.40 mg/dL and 4.0 ± 4.3 kg in the NaCl group (P = 0.30 and 0.57, respectively). Across efficacy and safety endpoints, we observed no significant difference between the 2 groups other than changes in serum sodium levels (-2.6 ± 2.7 in the placebo group and -0.3 ± 3.3 mEq/L in the NaCl group; P < 0.001) and in serum blood urea nitrogen levels (11 ± 15 in the placebo group; 3.1 ± 13 mEq/L in the NaCl group; P = 0.025). In this single-center study, liberal vs restrictive oral sodium chloride intake strategies did not impact the safety and efficacy of intravenous diuretic therapy in patients with AHF. (ClinicalTrials.gov registration NCT04334668.) [Display omitted] [ABSTRACT FROM AUTHOR]

• Electrical dyssynchrony occurs in 20% of patients with cardiac amyloidosis and is more common in elderly white patients with transthyretin amyloidosis and coronary artery disease. • QRS prolongation is not determined by the degree of left ventricular wall thickness. • Electrical dyssynchrony is associated with a higher New York Heart Association class, higher risk for permanent pacemaker implant and higher risk for all-cause mortality. Conduction-system involvement in cardiac amyloidosis (CA) is common. The prevalence, clinical correlates and impact on outcome related to ventricular electrical dyssynchrony in CA remain insufficiently elucidated. Data from a prospectively maintained registry of patients with CA diagnosed in the Cleveland Clinic's amyloidosis clinic was used to determine the frequency of electrical dyssynchrony (defined as a QRS > 130 msec). The relation with the clinical profile and clinical outcome was assessed. To determine the impact of hypertrophy on QRS prolongation, a QRS-matched cohort without CA was used for comparison of cardiac magnetic resonance imaging. A total of 1140 patients with CA (39% AL, 61% TTR) were evaluated, of whom 230 (20%) had electrical dyssynchrony. The type of conduction block was predominantly a right bundle branch block (BBB, 48%) followed by left BBB (35%) and intraventricular conduction delay (17%). Presence of transthyretin amyloidosis (ATTR-CA), older age, male gender, white race, and coronary artery disease were independently (P < 0.05 for all) associated with electrical dyssynchrony, and patients were more commonly prescribed a mineralocorticoid receptor antagonist. In ATTR-CA, specifically, every increase in ATTR-CA disease stage was associated with a 1.55-fold (1.23--1.95; P < 0.001) increased odds for electrical dyssynchrony. In a subset of patients with CA who underwent cardiac magnetic resonance imaging (n = 41), left ventricular mass index was unrelated to the QRS duration (r = 0.187; P = 0.283) in CA, in contrast to a non-CA QRS-matched cohort (r = 0.397; P < 0.001). Patients with electrical dyssynchrony were more symptomatic at initial presentation, as illustrated by a higher New York Heart Association class (P = 0.041). During a median follow-up of 462 days (IQR:138--996 days), a higher proportion of patients with electrical dyssynchrony died from all-cause death (P = 0.037) or developed a permanent pacing indication (3% vs 10.4%; P < 0.001) during follow-up. Electrical dyssynchrony is common in CA, especially in ATTR-CA, and is associated with worse functional status and clinical outcome. Given the high rate of permanent pacing indications at follow-up, additional studies are necessary to determine the best monitoring and pacing strategies in CA. [Display omitted] [ABSTRACT FROM AUTHOR]

Sarcopenia, a prevalent syndrome in heart failure (HF) and cancer, and subcutaneous adipopenia are associated with worse outcomes; however, they have not been studied in patients suffering from HF and cancer. We hypothesized that the presence of sarcopenia and subcutaneous adipopenia are associated with worse outcomes among patients with HF and cancer hospitalized for acute decompensated HF (ADHF). We included 409 consecutive patients hospitalized for ADHF from 2017 to 2020 with computed tomography of the chest one month before the discharge date. Semi-automatic measurements were made at T12 (Figure 1A) and adjusted for height squared to obtain skeletal muscle index (SMI) and subcutaneous adipose tissue index (SATI). To compare survival, patients with cancer were further grouped based on sarcopenia (lowest sex-stratified SMI tertile cutoffs of 29.6 cm2/m2 in males and 26.7 cm2/m2 in females) and subcutaneous adipopenia (lowest sex-stratified SATI tertile cutoffs of 22.7 cm2/m2 in males and 42.1 cm2/m2 in females). The mean age of our study cohort was 72±14 years, 44% were female, and 172 (42%) had a cancer history (39.5% metastatic). There were no significant differences in SMI or SATI between patients with versus without cancer, but patients with cancer had higher all-cause mortality (HR 1.48, 95%CI 1.14-1.92, p=0.004). During a median 14.8 (1.6-30.9) months of follow-up, all-cause mortality was higher in patients with cancer with sarcopenia (72.9%) versus without (57.5%) (Figure 1); this remained significant on adjustment for age, male sex, Caucasian race, coronary artery disease (CAD), chronic kidney disease, chronic obstructive pulmonary disease (COPD), metastasis, left ventricular ejection fraction, and NT-proBNP (HR 1.66, 95%CI 1.08-2.56, p=0.021). Furthermore, after similar multivariable adjustment, higher all-cause mortality was seen in patients with cancer with subcutaneous adipopenia (69.0%) versus without (59.6%) (HR 1.61, 95%CI 1.05-2.48, p=0.029). Metastasis remained an independent predictor of mortality in both models, along with CAD, COPD, and elevated NT-proBNP. Among patients with HF and cancer, lower skeletal muscle and subcutaneous adipose tissue quantity were independently associated with increased mortality risk after adjustment for predictors of disease severity. [ABSTRACT FROM AUTHOR]

Background: Iron deficiency (ID) is frequent and associated with diminished exercise capacity in heart failure (HF), but its contribution to unexplained dyspnea without a HF diagnosis at rest remains unclear.Methods and Results: Consecutive patients with unexplained dyspnea and normal echocardiography and pulmonary function tests at rest underwent prospective standardized cardiopulmonary exercise testing with echocardiography in a tertiary care dyspnea clinic. ID was defined as ferritin of <300 µg/L and a transferrin saturation of <20% and its impact on peak oxygen uptake (peakVO2), biventricular response to exercise, and peripheral oxygen extraction was assessed. Of 272 patients who underwent cardiopulmonary exercise testing with echocardiography, 63 (23%) had ID. For a similar respiratory exchange ratio, patients with ID had lower peakVO2 (14.6 ± 7.6 mL/kg/minvs 17.8 ± 8.8 mL/kg/min; P = .009) and maximal workload (89 ± 50 watt vs 108 ± 56 watt P = .047), even after adjustment for the presence of anemia. At rest, patients with ID had a similar left ventricular and right ventricular (RV) contractile function. During exercise, patients with ID had lower cardiac output reserve (P < .05) and depressed RV function by tricuspid s' (P = .004), tricuspid annular plane systolic excursion (P = .034), and RV end-systolic pressure-area ratio (P = .038), with more RV-pulmonary artery uncoupling measured by tricuspid annular plane systolic excursion/systolic pulmonary arterial pressure ratio (P = .023). RV end-systolic pressure-area ratio change from rest to peak exercise, as a load-insensitive metric of RV contractility, was lower in patients with ID (2.09 ± 0.72 mm Hg/cm2 vs 2.58 ± 1.14 mm Hg/cm2; P < .001). ID was associated with impaired peripheral oxygen extraction (peakVO2/peak cardiac output; P = .036). Cardiopulmonary exercise testing with echocardiography resulted in a diagnosis of HF with preserved ejection fraction in 71 patients (26%) based on an exercise E/e' ratio of >14, with equal distribution in patients with (28.6%) or without ID (25.4%, P = .611). None of these findings were influenced in a sensitivity analysis adjusted for a final diagnosis of HFpEF as etiology for the unexplained dyspnea.Conclusions: In patients with unexplained dyspnea without clear HF at rest, ID is common and associated with decreased exercise capacity, diminished biventricular contractile reserve, and decreased peripheral oxygen extraction. [ABSTRACT FROM AUTHOR]

Background: Alterations in myocardial mitochondrial function and metabolism have been implicated in the pathophysiology of heart failure with reduced ejection fraction (HFrEF). The impact of mechanical dyssynchrony and its alleviation through cardiac resynchronization therapy (CRT) on myocardial mitochondrial function and metabolism remain poorly understood.Methods: HFrEF patients with an indication for CRT underwent targeted metabolomic analysis of 84 energetic substrates at baseline (coronary sinus and peripheral venous blood). Mitochondrial membrane potential (Ψm) as an indicator of mitochondrial function was assessed non-invasively through 99mTC-sestamibi myocardial washout. Changes in peripheral metabolism and Ψm were assessed 6-months after CRT and their association with left ventricular remodeling and peakVO2 was assessed. Principle component analysis (PCA) was used as dimension reduction strategy for metabolic analysis.Results: Forty-five HFrEF-patients underwent CRT-implant (76% male, ejection fraction 29±6%). At baseline, PCA of coronary (CS) vs peripheral blood (PB) illustrated preferred cardiac uptake of β-hydroxybutyrate (CS vs PB-ratio=-78%; p<0.005) together with anaplerotic amino-acids, and glycolytic pyruvate breakdown to lactate. Baseline Ψm-dysfunction was associated with shift away from free fatty acids oxidation (FAO). Myocardial β-hydroxybutyrate extraction strongly associated with peakVO2 (-0.836; p<0.001). CRT improved Ψm (25±5% vs 18±6%; p=0.002), in parallel with metabolic remodeling, with increased reliance on FAO, and less reliance on β-hydroxybutyrate and glycolytic pyruvate breakdown to lactate. Changes in myocardial mitochondrial function and metabolism were associated with left ventricular reverse remodeling.Conclusion: HFrEF-patients exhibit baseline mitochondrial dysfunction, which is associated with alterations in myocardial substrate utilization, including less FAO, more reliance on ketone bodies, anaplerotic amino-acids and the breakdown of glycolytic pyruvate to lactate. CRT is capable of inducing mitochondrial and metabolic reverse remodeling which is associated with cardiac morphology changes. [ABSTRACT FROM AUTHOR]

Background: Discontinuous intrarenal venous flow patterns, as assessed by renal Doppler ultrasound examination, are associated with changes in hemodynamics such as volume expansion and poorer diuretic response in patients with heart failure (HF). We aimed to study intrarenal venous and arterial flow patterns after decongestive treatment in patients with acute HF.Methods and Results: Fifteen patients with acute HF were enrolled. Intrarenal venous and arterial flow patterns were assessed at baseline, 1 hour after administration of loop diuretics, at day 2 and day 3. Among patients hospitalized for acute HF, 13 (87%) had a discontinuous venous flow pattern at admission. After decongestive treatment, a significant improvement of the venous impedance index (P = .021) and venous discontinuity index (P = .004) was observed at day 3 compared with baseline. There was no effect on the intrarenal arterial flow patterns.Conclusions: In patients who exhibit discontinuous renal venous flow patterns hospitalized for decongestive treatment owing to acute HF led to a normalization of intrarenal venous flow to a continuous pattern. [ABSTRACT FROM AUTHOR]

Introduction: Limited data are available concerning the effect of severe chronic kidney disease (CKD) on the response to cardiac resynchronization therapy (CRT) because these patients are commonly excluded from trials. Therefore, we aimed to assess the effect of CRT on renal function, reverse remodeling and outcome across all stages of CKD in a large patient population of recipients of CRT.Methods: We retrospectively evaluated 798 consecutive patients with heart failure who were undergoing CRT implantation between October 2008 and September 2016. Renal function data were available at baseline and at 6 months following CRT. Remodeling based on left ventricular end diastolic volume/left ventricular ejection fraction (LVESV/LVEF) and clinical outcome was assessed using a combined endpoint of all-cause mortality and hospitalization because of heart failure.Results: Median baseline estimated glomerular filtration rate was 62.8 (43.6-77.8) mL/min/1.73 m2. Of the patients, 33.6% were in CKD stage 3, 11.0% in stage 4 and 1.1% in stage 5. LVEF and LVESV improved across all CKD stages; however, patients with CKD stages 1 and 2 exhibited a greater degree of improvement in LVEF (median 15% vs 10%, P < 0.001) and LVESV (median -37.2% vs -29.9%, P < 0.001) compared to patients with CKD stages 3-5. Despite a greater degree of reverse remodeling in CKD stages 1 and 2, the most accurate cut-off of remodeling predicting good clinical outcome was lower for patients with CKD stage 3-5, respectively: 5.5% vs 9.5% (LVEF) and -6.67% vs -12.41% (LVESV).Conclusions: CRT results in reverse remodeling across all stages of CKD, although to a lesser extent in patients with renal dysfunction (CKD stage 3-5). However, patients with CKD derive benefit on outcome at a lesser degree of remodeling. [ABSTRACT FROM AUTHOR]

Background: Progressive plasma volume (PV) expansion is a hallmark of chronic heart failure (HF), ultimately contributing to decompensated heart failure. Monitoring PV might offer prognostic information and might be a target for tailored therapy.Methods and Results: The correlation between technetium-99 (99Tc)-labeled red blood cell measured PV and calculated PV was first determined in a validation cohort. The relationship between PV status (PVS; a marker how much actual PV deviated from the ideal PV) and outcome was analyzed with the use of Cox proportional modeling in a prospective chronic HF (CHF) population (the outcome cohort). Thirty-one HF patients were included in the validation cohort. Calculated PV correlated well with 99Tc-measured PV (r = 0.714; P = .001). A total of 1173 patients (HF with reduced ejection fraction [HFrEF]: n = 872; HF with mid-range EF [HFmrEF]: n = 229; HF with preserved EF [HFpEF]: n = 72) were prospectively included in the outcome cohort. The mean PVS in the outcome cohort was -6.7% ± 10%, indicating slight PV contraction. Higher PVS was independently associated with increased risk for HF hospitalization and all-cause mortality (hazard ratio 1.016; 95% confidence interval 1.006-1.027 per 1% increase in PVS; P = .002). Receiver operating characteristic curve analysis indicated that a PVS of -6.5% optimally predicted absence of adverse outcome. Hazard ratio analysis indicated that CHF patients were less equipped in tolerating PV expansion in comparison to PV contraction. The use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and mineralocorticoid receptor antagonists were independently associated with a higher odds of having an optimal PVS in HFrEF and HFmrEF (all P < .05), but not in HFpEF.Conclusions: Calculated PV correlates well with measured PV in HF patients. An increase in PV is independently associated with a higher risk of adverse outcome, and a slight contraction of the predicted PV seems to be related to less adverse events. Higher dosages of renin-angiotensin-aldosterone blockers are associated with higher odds of having an optimal PV status. [ABSTRACT FROM AUTHOR]

Background: Cardiac resynchronization therapy (CRT) improves mortality and morbidity on top of optimal medical therapy in heart failure with reduced ejection fraction (HFrEF). This study aimed to elucidate the association between neurohumoral blocker up-titration after CRT implantation and clinical outcomes.Methods and Results: Doses of angiotensin-converting enzyme inhibitors (ACE-Is), angiotensin receptor blockers (ARBs), and beta-blockers were retrospectively evaluated in 650 consecutive CRT patients implanted from October 2008 to August 2015 and followed in a tertiary multidisciplinary CRT clinic. All 650 CRT patients were on a maximal tolerable dose of ACE-I/ARB and beta-blocker at the time of CRT implantation. However, further up-titration was successful in 45.4% for ACE-I/ARB and in 56.8% for beta-blocker after CRT-implantation. During a mean follow-up of 37 ± 22 months, a total of 139 events occurred for the combined end point of heart failure admission and all-cause mortality. Successful, versus unsuccessful, up-titration was associated with adjusted hazard ratios of 0.537 (95% confidence interval 0.316-0.913; P = .022) for ACE-I/ARB and 0.633 (0.406-0.988; P = .044) for beta-blocker on the combined end point heart failure admission and all-cause mortality. Patients in the up-titration group exhibited a similar risk for death or heart failure admission as patients treated with the maximal dose (ACE-I/ARB: P = .133; beta-blockers: P = .709).Conclusions: After CRT, a majority of patients are capable of tolerating higher dosages of neurohumoral blockers. Up-titration of neurohumoral blockers after CRT implantation is associated with improved clinical outcomes, similarly to patients treated with the guideline-recommended target dose at the time of CRT implantation. [ABSTRACT FROM AUTHOR]

Background: Intravascular volume overload and depletion as well as anemia are associated with increased hospital admissions and mortality in patients with heart failure. This study aimed to accurately measure plasma volume and red cell mass (RCM) in stable patients with chronic heart failure with reduced ejection fraction (HFrEF) and gain more insight into plasma volume regulation and anemia in stable conditions of HFrEF.Methods and Results: Plasma volume and RCM measurement based on 99Tc-labeled red blood cells, venous blood sample,s and clinical parameters were obtained in 24 stable HFrEF patients under optimal medical therapy. Measured plasma volume values were compared with predicted values based on body surface area. Plasma volume was on average normal (99.98% of predicted) but heterogeneously distributed (variations of 81%-133%). Neurohumoral activation and medication use were not associated with plasma volume status. Furthermore, anemia based on actual measurement of RCM was present in up to 75% of subjects, but rarely hemodilutional.Conclusions: In stable chronic HFrEF patients under optimal medical therapy, plasma volume is overall normal but heterogeneously distributed. Anticipated factors such as neurohumoral activation and heart failure medication were not associated with plasma volume. Furthermore, anemia is more common than as assessed by hemoglobin. [ABSTRACT FROM AUTHOR]

Little information is available on the prognostic relevance of cardiac hemodynamic cut-offs in cardiac amyloidosis (CA) and its subtypes. Consecutive patients diagnose with light chain (AL)-CA or transthyretin (ATTR)-CA undergoing right heart catheterization (RHC) were analysed. Prognostic relevance of classic hemodynamic cut-offs of cardiac-index (CI<2.2L/min/m2), Pulmonary-capillary-wedge pressure (PCWP>18mmHg), right atrial pressure (RAP>8mmHg) and mean Pulmonary artery pressure (mPAP≥25mmHg or pulmonary hypertension=PH) with all-cause mortality was assessed. 469 CA-patients under RHC (AL-CA=42% and ATTR-CA=52%) of whom 69%, 64% and 79% had respectively elevated RAP, PCWP and PH. The classic hemodynamic cut-offs for RAP and mPAP did not identify patients at higher risk for adverse outcome (p=0.077, respectively p=0.129). However ROC-curve analysis identified a cut-off of respectively 14mmHg for RAP and 35mmHg for mPAP, to perform better in detecting all-cause mortality (p<0.05 for both, see figure). Reduced CI occurred in 55% of patients and was the strongest independent predictor of both outcome (all-cause mortality) and functional status (baseline NYHA-class), and this on top of mPAP or RAP. Presence of a low CI could non-invasively be detected by identifying patients with a single digit global longitudinal strain value. The only hemodynamic variable differing between ATTR-CA and AL-CA was PCWP being higher in the latter. Hemodynamic variables are grossly abnormal in CA, but values for filling pressure might warrant differential definitions. CI is the hemodynamic variable most strongly associated with outcome and functionality. [ABSTRACT FROM AUTHOR]

Conduction system involvement in cardiac amyloidosis (CA) is common. The prevalence, clinical correlates and impact on outcome related to ventricular electrical dyssynchrony (ED) in CA remain insufficiently elucidated. Data from a prospectively maintained registry of CA patients diagnosed in the Cleveland Clinic amyloidosis clinic was used to determine the frequency of ED (defined as a QRS >130msec). The relation with the clinical profile and clinical outcome was assessed. To determine the impact of hypertrophy on QRS prolongation a QRS matched cohort without CA was used for cardiac magnetic resonance imaging comparison. A total of 1,140 CA-patients (39%AL, 61% TTR) were evaluated, of whom 230 (20%) had ED. The type of conduction block was predominantly a right bundle branch block (BBB, 48%) followed by left BBB (35%) and intraventricular conduction delay (17%). Presence of transthyretin amyloidosis (ATTR-CA), older age, Caucasian descent, and coronary artery disease were independently (p<0.05 for all) associated with ED and patients were more often prescribed mineralocorticoid receptor antagonist. In ATTR-CA specifically, every increase in ATTR-CA disease stage was associated with a 1.55-fold (1.23-1.95, p<0.001) increased odds for ED. In a subset of CA patients who underwent cardiac magnetic resonance imaging, the degree of hypertrophy measured by left ventricular mass index was unrelated to the QRS duration (r=0.187, p=0.283) in CA, in contrast to a non-CA QRS-matched cohort (r=0.397, p<0.001). Patients with ED were more symptomatic at initial presentation as illustrated by a higher NYHA class (p=0.034). During a median follow-up of 462 days (IQR:138-996 days), a higher proportion of ED patients died from all-cause death (p=0.037, figure panel A) or developed a permanent pacing indication (3% vs 10.4%, p<0.001, figure panel B) during follow-up. ED is common in CA especially in ATTR-CA and is associated with worse functional status and clinical outcome. Given the high rate of permanent pacing indications at follow-up, additional studies are necessary to determine best monitoring and pacing strategies in CA. [ABSTRACT FROM AUTHOR]

Diuretic resistance (DR) is associated with in-hospital complications and worse long-term clinical outcomes. Recently, the BAN-ADHF score, previously developed to evaluate risk for DR, has been validated for increased mortality, but its prediction of diuretic response has not been evaluated in an external cohort. Here, we present the application of BAN-ADHF scores as well as implementation with a novel loop diuretic sliding scale for patients admitted with ADHF. A retrospective analysis of 275 patients admitted to RNF for ADHF with NT pro-BNP >1,000. BAN-ADHF score is comprised of: BUN, creatinine, NT pro-BNP, age, diabetes and DBP, HF hospitalization, and atrial fibrillation. Loop diuretic sliding scale was adapted from the CARRESS trial. Primary outcome of interest was diuretic efficiency as measured by both 24-hour urine output (UOP) and weight loss per 40 mg IV furosemide equivalents. Other secondary outcomes collected included weight change at discharge, UOP, and achievement of UOP goal of > 3L in 24 hours. BAN-ADHF scores were calculated with a median score of 9 with an IQR of 7-13. Increasing BAN-ADHF score was associated with decreased diuretic efficiency for both weight loss (r = -0.23, p = 0.002) and urine output as measured at 24 hours (r = -0.33, p <0.0001) and 72 hours of admission (r = -0.31, p <0.0001). Patients were dichotomized with a cutoff BAN-ADHF score of ten to establish high/low risk groups for diuretic resistance. The high-risk group had higher loop dosing (see Table 1, p = 0.005), decreased rate of attaining the >3L UOP (18% vs 35%, diff 17%, p = 0.001), and lower UOP (2,033 vs 2,620 mL, diff 587 mL, p = 0.006). BAN-ADHF scores were compared to CKD and NT pro-BNP alone in prediction of diuretic efficiency and achieving UOP goals. As for the loop sliding scale, 161/271 (59.4%) patients were dosed at goal of x2 home dose (x2.5 if CKD or BAN-ADHF > 10). Comparing to those below goal, patients receiving goal-doses had increased 24-hour UOP (2,608 vs 1,1941 mL, diff 667, p = 0.002), increased likelihood of UOP goal (34% vs 15%, diff 22%, p < 0.001), increased weight loss at discharge (7.17 kg vs. 5.89 kg, diff 1.28 kg, p = 0.036), and decreased length of stay (9.0 vs 11.4 days, diff 2.4, p = 0.014). BAN-ADHF score was externally validated for its association with diuretic efficiency and demonstrated improved diagnostic yield as compared to CKD in predicting UOP and weight change during hospitalization. In addition, preliminary retrospective application of the furosemide sliding scale proposed is associated with increased weight loss and improved rates of obtaining goal urine output. Further studies should aim to assess the utility of prospectively applying BAN-ADHF and furosemide sliding scale to ADHF. [ABSTRACT FROM AUTHOR]

Sarcopenia and obesity have been independently associated with worse outcomes in various clinical settings. With the alarming rise in obesity seen worldwide, sarcopenia is increasingly accompanied by high adiposity, termed sarcopenic obesity (SO). Given the poor outcomes of sarcopenia and obesity, we hypothesized that their coexistence would lead to synergistically worse outcomes in patients hospitalized for acute decompensated heart failure (ADHF). Patients hospitalized for ADHF (n=200) from January 1 of 2017 to 2019 with computed tomography of the abdomen/pelvis within 30 days before discharge were studied. Semi-automatic measurements of skeletal muscle mass (SMM) and visceral adipose tissue (VAT) cross-sectional areas were made at L3. SMM was adjusted using height squared to get skeletal muscle index (SMI). Sarcopenia was defined as the lowest sex-stratified SMI tertile. Obesity was defined by VAT cancer cut-offs of 163.8 cm2 in males and 80.1 cm2 in females. The prevalence of sarcopenia was 19%, obesity 41%, and SO 11%. No significant difference was seen for in-hospital mortality or length of stay (p=0.481), but all-cause mortality during a median 713 days of follow-up differed among the groups (p=0.001; Figure 1). Patients with SO had the highest risk for all-cause mortality (HR: 2.03; 95%CI: 1.13-3.64; p=0.018) while those with sarcopenia (HR: 1.38; 95%CI: 0.83-2.28; p=0.215) alone fared worse than obesity (HR: 0.70, 95%CI: 0.44-1.11; p=0.126) alone, although the latter differences did not reach statistical significance in comparison to controls (no obesity or sarcopenia). Controls had the best long-term outcome despite having a significantly higher NTproBNP in comparison to patients with obesity (7,121 [1,859-7,121] vs 2,711 [1,010-6,676]; p=0.001) but did not differ from patient with sarcopenia (7,126 [4,188-13,538]; p=0.272) or sarcopenic obesity (5,253 [3,136-18,352]; p=0.076). Sarcopenic obesity was associated with increased mortality in patients hospitalized with ADHF. Despite having a natriuretic peptide deficit, patients with obesity alone had better outcomes. The presence of sarcopenia seems to diminish the natriuretic peptide deficit partially. Further work is underway to characterize better the effect of SO in ADHF. [ABSTRACT FROM AUTHOR]

Limited information is available about the short and long-term outcomes in electrical storm (ES)-induced cardiogenic shock (CS) and its predictors. This is a retrospective, single-center cohort study of consecutive patients with ES admitted to the Cardiac Intensive Care Unit (ICU) between 2015 and 2020. The proportion of ES patients who developed CS was adjudicated, and clinical predictors of in-hospital ventricular arrhythmia (VA)-related mortality and one-year all-cause mortality were investigated. Of the 214 patients with a primary diagnosis of ES admitted to the cardiac ICU, 33.6% developed CS. Reduced left ventricular ejection fraction, admission lactate, absence of an implantable-cardioverter defibrillator, and admission central venous pressure were independently associated with development of CS (p<0.03 for all, see central figure). Based on these variables, a FLIC-score was developed to predict ES-induced CS (AUC=0.949). Patients who developed CS had a 11.3-fold (95% CI 2.7-12.8) increased odds for in-hospital VA-related mortality and 9.4-fold (95% CI 4.0-22.4) increased odds for in hospital all-cause mortality. A FLIC-score above 0.62 was associated with a 6.2- and 5.8-fold increased odds for respectively similar endpoints. Patients with ES-induced CS received more treatment modalities to manage the ES (4.5±1.8 vs 2.3±1.2, p<0.001) and had longer length of stay (14 [8-27] vs 8 [5-13], p<0.001) than patients without CS. Of different treatment modalities used, early ablation was associated with a lower in hospital mortality rate. Interestingly if patients with ES-induced CS survived to discharge, their outcomes were similar to those without CS at one year. Cardiogenic shock in ES is a frequent and potentially life-threatening complication with high short-term mortality. A novel risk score could identify patient at risk, generating a potential for early risk based interventions. Prospective randomized studies are necessary to determine if early application of certain treatment modalities could improve clinical outcome. [ABSTRACT FROM AUTHOR]

Background: Cardiac resynchronization therapy (CRT) improves morbidity and mortality in heart failure with reduced ejection fraction (HFrEF) and electrical dyssynchrony. CRT patients in clinical practice are older compared with clinical trials.Objective: To investigate clinical response, reverse remodeling, outcome, and mode of death in octogenarians receiving CRT.Methods: Baseline characteristics, change in New York Heart Association (NYHA) functional class, reverse ventricular remodeling, heart failure readmissions, all-cause mortality, and mode of death were evaluated in CRT patients with comparison between octogenarians and nonoctogenarians. In addition, annual mortality rates of octogenarians undergoing CRT were compared with age-matched control subjects from the general population with the use of national actuarial tables.Results: A total of 686 patients, including 178 octogenarians (26%), were followed for 38 ± 22 months. Octogenarians exhibited a similar change in NYHA functional class (P = .640), left ventricular ejection fraction increase (P = .796), and decrease in end-diastolic (P = .441) and end-systolic (P = .312) diameter compared with their younger counterparts undergoing CRT. Octogenarians had a higher all-cause mortality risk (P < .001), but heart failure readmission risk did not differ (hazard ratio 0.916, 95% confidence interval 0.638-1.313; P = .632). A higher proportion of noncardiac deaths was observed in octogenarians (74%) versus younger patients (50%; P = .022), with worsening heart failure rather than malignant tachyarrhythmia being the main cardiac cause of death. Compared with an age-matched sample from the general population, octogenarians receiving CRT had an equivalent annual mortality rate (log-rank test: P = .444).Conclusions: Octogenarians retain the ability to mount a significant symptomatic and ventricular remodeling response after CRT, resulting in survival similar to the general age-matched population. [ABSTRACT FROM AUTHOR]

It remains unclear if medical therapy remains necessary in HF patients with myocardial recovery after CRT in whom conduction delay is thought to be the main driver. This was a prospective multicenter, open-label, double randomized pilot trial to investigate the safety of neurohumoral (NH) blocker withdrawal in HF patients with recovered ejection fraction (HFrecEF) after CRT. Subjects were randomized to systematic withdrawal of RAAS inhibitors and beta blockers (BB) versus continuation of treatment. The primary endpoint was a recurrence of negative remodeling defined by an increase in left ventricular end systolic volume index (LVESVi) of more than 15% at 24 months. The secondary endpoint is a composite safety endpoint of all-cause mortality, HF related hospitalizations and incidence of sustained ventricular arrhythmias at 24 months. The primary analysis was by intention to treat. Results : Between September 24, 2014, and February 15, 2017, 80 subjects were consecutively enrolled and randomized between 4 groups (continuation of NH blocker therapy (n=20), withdrawal of RAAS inhibitors (n=20), withdrawal of BB (n=20) and withdrawal of RAAS inhibitors and BB (n=20)). Of the 80 subjects, 6 (7.5%) met the primary endpoint of recurrence of negative remodeling based on an increase of >15% in LVESVi. The secondary endpoint occurred in 4 subjects (5%) within 24 months. There was no difference between the 4 groups regarding the primary (log rank p=0.497) and secondary endpoint (log rank p=0.507) (Figure 1). There were no hospital admissions due to HF or cardiac deaths during this time period in any subject. However, re-initiation of therapy occurred in 16 (20%) subjects due to hypertension or supraventricular arrhythmias. Compared to continuation, withdrawal of NH blockers in patients with myocardial recovery after CRT is not associated with a recurrence of LV dilatation or HF after 2 years. However, the feasibility of NH blocker withdrawal is hampered because of hypertension and supraventricular arrhythmias. [ABSTRACT FROM AUTHOR]

Signs and symptoms of congestion are the predominant reason for hospital admission with acute heart failure (AHF). Diuretics are mainstay treatment, but their optimal type and dose regimen remains unclear. Acetazolamide in addition to loop diuretics increases natriuresis without further neurohumoral activation, potentially improving decongestion and outcomes in AHF. This prospective, 2-center study included 34 AHF patients on loop diuretics with volume overload. All patients had a serum sodium concentration <135 mmol/L and/or serum urea/creatinine ratio >50 and/or admission serum creatinine increased with >0.3 mg/dL compared to baseline. Patients were randomized towards acetazolamide 500 mg OD plus bumetanide 1-2 mg BID versus high-dose loop diuretics (bumetanide BID with bolus dose equal to oral maintenance dose). The primary end-point was natriuresis after 24h. Natriuresis after 24h was similar in the combinational treatment versus loop-diuretic only arm (264±126 versus 234±133 mmol, respectively; P-value=0.515). Loop diuretic efficiency, defined as natriuresis corrected for loop diuretic dose, was higher in the group receiving acetazolamide (84±46 versus 52±42 mmol/mg bumetanide, respectively; P-value=0.048; Figure). More patients in the combinational treatment arm had an increase in serum creatinine levels >0.3 mg/dL (P-value=0.046). NT-proBNP reduction and peak neurohumoral activation within 72h were comparable among treatment arms. Median time to all-cause mortality or heart failure readmission was 273 versus 803 days in the group receiving high-dose loop diuretic monotherapy versus acetazolamide with low-dose loop diuretics, which favoured the latter group but was not statistically significant (P-value=0.098). Addition of acetazolamide increases the natriuretic response to loop diuretics with similar neurohumoral responses compared to an increase in loop diuretic dose in AHF at high risk for diuretic resistance. ClinicalTrials.gov identifier: NCT01973335. [ABSTRACT FROM AUTHOR]

Volume overload is a hallmark feature of HF. The pressure-based assessment of volume status has gained popularity in HF with the use of implantable devices, yet its accuracy to detect early intravascular volume expansion is unclear. To study the relationship between intravascular volume and intra-cardiac filling pressures in the setting of stable HFrEF. 40 euvolemic HFrEF patients (10 subjects with a PAC), underwent intravascular volume expansion with 1 liter hydroxyl-ethyl-starch over 3 hours with coinciding intravascular volume measurements (technetium (99Tc)-labeled red blood cell technique). Intravascular blood volume increased from 5.0±1.0 L to 5.7±1.0 L (p<0.0001). No change in clinical status or NT-proBNP levels (670[225;1383] ng/L vs 615[217;521] ng/L; p=0.86) was observed. No significant changes in echocardiographic indices of cardiac filling pressures were present (Fig 1). Invasively measured RAP and PAWP increased significantly immediately after start of infusion (4±2 mmHg to 8±4 mmHg; p=0.01 and 10±3 mmHg to 15±6 mmHg; p=0.01), decreased afterwards and remained stable for 3 hours (6±2 mmHg and 14±4 mmHg), indicative of cardiovascular volume reserve (Fig 2A). The accuracy of cardiac filling pressure (estimates) to predict intravascular volume expansion was very low (all AUC <0.65; fig 2B). Euvolemic HFrEF patients can tolerate an intravascular volume expansion of 0.7L without signs and symptoms of HF. Due to this cardiovascular volume reserve, estimates of cardiac filling pressures might be of limited value to reliable assess intravascular volume changes. [ABSTRACT FROM AUTHOR]