Prognostic implications of volume status assessed by blood volume analysis in ambulatory heart failure.

The prognostic implications of intravascular volume status assessed by blood volume analysis (BVA) in ambulatory heart failure (HF) remain uncertain. The incremental benefits of assessing volume status, beyond the well-established filling pressures, in predicting HF outcomes are unknown.

Patient Sex Impacts Volume Phenotypes and Hemodynamics in Chronic Heart Failure: A Multicenter Analysis.

BACKGROUND: Quantitative methods have shown clinically significant heterogeneity in blood volume (BV) profiles in patients with chronic heart failure (HF). How patients' sex might impact this volume heterogeneity and its relationship to cardiac hemodynamics remains to be defined. METHODS: Retrospective analysis of clinical and quantitative BV, plasma volume (PV) and red blood cell (RBC) mass data was undertaken across 3 medical centers. BV was quantitated using nuclear medicine I-131-labeled plasma albumin indicator-dilution methodology with cardiac hemodynamics obtained within 24 hours. RESULTS: In an analysis of 149 males and 106 females, absolute BV was greater, on average, in males (6.9 ± 1.7 vs 5.0 ± 1.2 liters; P < 0.001); however, a wide range in BVs was demonstrated in both sexes (2.9-14.5 liters). Male sex was associated with higher prevalence of large (+ 25% of normal) BV and PV expansions (36% vs 15% and 51% vs 21%, respectively; both P < 0.001). In contrast, female sex was associated with higher prevalence of normal total BV (44% vs 27%; P = 0.005), PV (54% vs 27%; P < 0.001), hypovolemia (23% vs 11%; P = 0.005), and true anemia (42% vs 26%; P < 0.001). Cardiac hemodynamics differed by sex, but only modest associations were demonstrated between volume profiles and cardiac filling pressures. CONCLUSIONS: Findings support unique intravascular volume profiles reflecting sex-specific differences in the prevalence and distributions of total BV, PV and RBC mass profiles in patients with chronic HF. This underscores the importance of recognizing patients' sex as a significant factor influencing volume homeostasis, which needs to be taken into account to individualize volume-management strategies effectively.

Non-invasive heart failure monitoring: leveraging smart scales and digital biomarkers to improve heart failure outcomes.

Heart failure (HF) is a significant global concern, impacting patient morbidity, mortality, and healthcare costs. Guideline-directed medical therapy and various preventive measures have proven effective in improving clinical outcomes and reducing HF hospitalizations. Recent data indicates that remote HF monitoring facilitates early detection of HF decompensation by observing upstream events and parameters before clinical signs and symptoms manifest. Moreover, these innovative devices have been shown to decrease unnecessary HF hospitalizations and, in some cases, provide predictive insights before an actual HF incident. In this review, we aim to explore the data regarding smart scales and digital biomarkers and summarize both FDA-approved devices and emerging technologies by assessing their clinical utility, mechanism of HF decompensation detection, and ongoing trials. Furthermore, we also discuss the future trend of integrating these devices into routine clinical practice to improve patient clinical outcomes.

Effects of bromocriptine in peripartum cardiomyopathy: a systematic review and meta-analysis.

Peripartum cardiomyopathy (PPCM) is a rare but potentially life-threatening form of heart failure (HF). Bromocriptine, a dopamine D2 agonist, has been used as an adjunctive treatment for PPCM with controversial benefits. A comprehensive literature search was conducted through June 2021. We included studies comparing the outcomes of PPCM with or without bromocriptine use. Pooled risk ratio (RR) with 95% confidence intervals (CI) and I2 statistics were calculated. Composite major adverse outcomes were defined by a composite of death, need for advanced HF therapies, persistent New York Heart Association (NYHA) functional class III/V, or left ventricular ejection fraction (LVEF) ≤ 35% at 6-month follow-up. LVEF recovery was defined by improvement of LVEF to more than 50%. Eight studies (two randomized-controlled, six observational) involving 593 PPCM patients were included. Bromocriptine use was associated with significantly higher survival (91.6% vs. 83.9%, RR 1.11 p = 0.02). Baseline LVEF was not significantly different between the groups. LVEF at follow-up was significantly higher in the bromocriptine group (53.3% vs. 41.8%, p < 0.001). There was no significant association between bromocriptine use and lower composite major adverse outcomes (13.7% vs. 33.3%, RR 0.60 p = 0.54) or LVEF recovery (46.9% vs. 46.8%, RR 0.94 p = 0.74). In conclusion, the addition of bromocriptine to standard HF treatment in PPCM was associated with significantly higher survival and higher LVEF improvement. No association with lower composite adverse clinical outcomes or LVEF recovery was seen. The findings, although encouraging, warrant larger randomized-controlled studies.

Pre-operative atrial fibrillation and early right ventricular failure after left ventricular assist device implantation: a systematic review and meta-analysis.

BACKGROUND: Right ventricular failure (RVF) remains a major cause of morbidity and mortality after left ventricular assist device (LVAD). Atrial fibrillation (AF) is known for its deleterious effects on cardiac function and hemodynamics. The association of pre-operative AF with the risk of early post-LVAD RVF has not been well described. METHOD: A comprehensive literature search was performed through April, 9 2021. Cohort studies comparing the risk of post-operative RVF and/or need for right ventricular assist device (RVAD) after LVAD in patients with or without AF were included. Pooled odds ratio (OR) with 95% confidence intervals (CI) and I2 statistic were calculated using the random-effects model. RESULTS: Six studies were included in the analysis. Post-operative RVF was reported in 5 studies (1,841 patients) and RVAD use was reported in 4 studies (1,355 patients). There is a non-significant trend toward a higher risk of post-operative RVF in the AF group (pooled OR=1.25, 95%CI=0.99-1.58). No significant association between AF and RVAD use is noted (pooled OR=1.17, 95%CI=0.82-1.66). CONCLUSIONS: Pre-operative AF is not significantly associated with higher risks of post-operative RVF and RVAD use after LVAD implantation, although the trend toward higher post-operative RVF is observed in patients with pre-operative AF. Additional research using a larger study population is warranted to better understand the association of pre-operative AF and the development of post-LVAD RVF.

Early diuretic strategies and the association with In-hospital and Post-discharge outcomes in acute heart failure.

BACKGROUND: Decongestion is a primary goal during hospitalizations for decompensated heart failure (HF). However, data surrounding the preferred route and strategy of diuretic administration are limited with varying results in prior studies. METHODS: This is a retrospective analysis using patients from ASCEND-HF with a stable diuretic strategy in the first 24 hours following randomization. Patients were divided into three groups: intravenous (IV) continuous, IV bolus and oral strategy. Baseline characteristics, in-hospital outcomes, 30-day composite cardiovascular mortality or HF rehospitalization and 180-day all-cause mortality were compared across groups. Inverse propensity weighted modeling was used for adjustment. RESULTS: Among 5,738 patients with a stable diuretic regimen in the first 24 hours (80% of overall ASCEND trial), 3,944 (68.7%) patients received IV intermittent bolus administration of diuretics, 799 (13.9%) patients received IV continuous therapy and 995 (17.3%) patients with oral administration. Patients in the IV continuous group had a higher baseline creatinine (IV continuous 1.4 [1.1-1.7]; intermittent bolus 1.2 [1.0-1.6]; oral 1.2 [1.0-1.4] mg/dL; P <0.001) and high NTproBNP (IV continuous 5,216 [2,599-11,603]; intermittent bolus 4,944 [2,339-9,970]; oral 3,344 [1,570-7,077] pg/mL; P <0.001). There was no difference between IV continuous and intermittent bolus group in weight change, total urine output and change in renal function till 10 days/discharge (adjusted P >0.05 for all). There was no difference in 30 day mortality and HF readmission (adjusted OR 1.08 [95%CI: 0.74, 1.57]; P = 0.701) and 180 days mortality (adjusted OR 1.04 [95%CI: 0.75, 1.43]; P = 0.832). CONCLUSION: In a large cohort of patients with decompensated HF, there were no significant differences in diuretic-related in-hospital, or post-discharge outcomes between IV continuous and intermittent bolus administration. Tailoring appropriate diuretic strategy to different states of acute HF and congestion phenotypes needs to be further investigated.

Phosphodiesterase-5 Inhibitors and Outcomes During Left Ventricular Assist Device Support: A Systematic Review and Meta-Analysis.

BACKGROUND: Phosphodiesterase-5 inhibitors (PDE5i) have been used to treat pulmonary hypertension and right ventricular failure in patients with left ventricular assist devices (LVAD). The effects of PDE5i on post-LVAD outcomes including hemocompatibility-related adverse events are not well-established. This systematic review and meta-analysis aims to evaluate the effects of PDE5i on post-LVAD outcomes. METHODS AND RESULTS: A comprehensive literature search was conducted using Pubmed and Embase databases from inception through November 25, 2020, to compare post-LVAD outcomes in patients with or without PDE5i use. Pooled odds ratio (OR) with 95% confidence intervals (CI) and I2 statistic were calculated. Thirteen observational studies were included in this analysis. The use of PDE5i was not significantly associated with lower postoperative right ventricular failure (OR 0.38, 95% CI 0.02-5.96, P = .41). There was no significant association between PDE5i and gastrointestinal bleeding (OR 1.23, 95% CI 0.76-1.98, P = .2), overall stroke (OR 0.60, 95% CI 0.21-1.68, P = .17), ischemic stroke (OR 0.61, 95% CI 0.09-4.07, P = .38), or pump thrombosis (OR 0.71, 95% CI 0.14-3.54, P = .46). CONCLUSIONS: Our meta-analysis showed no significant association between PDE5i and post-LVAD right ventricular failure. Despite the antiplatelet effects of PDE5i, there was no significant association between PDE5i and gastrointestinal bleeding, overall stroke, ischemic stroke, or pump thrombosis. Randomized controlled studies are warranted to evaluate the net benefits or harms of PDE5i in the LVAD population.

In-hospital outcomes after bariatric surgery in patients with heart failure.

Based on the largest publicly available all-payer inpatient database in the United States, this study sought to evaluate real-world outcomes after bariatric surgery among patients with heart failure.

Non-Transfemoral Transcatheter Aortic Valve Replacement Approach is Associated with a Higher Risk of New-Onset Atrial Fibrillation: A Systematic Review and Meta-Analysis.

BACKGROUND: New-onset atrial fibrillation (NOAF) is a frequent arrhythmic complication following transcatheter aortic valve replacement (TAVR). Choice of access routes for TAVR could be a factor that determines the risk of NOAF although the data is still not well-characterised. We aimed to assess the association between different access routes for TAVR (transfemoral versus non-transfemoral) and the risk of NOAF. METHODS: A comprehensive literature review was performed through September 2018 using EMBASE and Medline. Eligible studies must compare the incidence of NOAF in patients without pre-existing atrial fibrillation who underwent TAVR. Relative risk (RR) and 95% confidence intervals (CI) were extracted from each study and combined together using the random-effects model, generic inverse variance method of DerSimonian and Laird. RESULTS: Seven (7) retrospective studies with 18,425 patients who underwent TAVR (12,744 with the transfemoral approach and 5,681 with the non-transfemoral approach) met the eligibility criteria. After the procedures, 2,205 (12.0%) patients developed NOAF (656 [5.1%] patients in the transfemoral group and 1,549 [27.3%] patients in the non-transfemoral group). There was a significant association between the non-transfemoral approach and an increased risk of NOAF with the pooled RR of 2.94 (95%CI, 2.53-3.41; p < 0.00001). Subgroup analysis showed the highest risk of NOAF in the transapical subgroup with the pooled RR of 3.20 (95% CI, 2.69-3.80; I2 33%). CONCLUSIONS: A significantly increased risk of NOAF following TAVR among those who underwent a non-transfemoral approach compared with transfemoral approach was observed in this meta-analysis.

Modes of death and clinical outcomes in adult patients with hypertrophic cardiomyopathy in Thailand.

BACKGROUND: There are limited data about modes of death and major adverse cardiovascular events (MACEs) in patients with hypertrophic cardiomyopathy (HCM) in South East Asian population. The aim of the study was to examine modes of death and clinical outcomes in Thai patients with HCM. METHODS: Between January 1, 2009 and December 31, 2013, 166 consecutive patients with HCM diagnosed in our institution were evaluated. Five patients were excluded because of non-Thai ethnic groups (n = 3) and diagnosis of myocardial infarction at initial presentation documented by coronary angiography (n = 2). The final study population consisted of 161 patients with HCM. HCM-related deaths included: (1) sudden cardiac death (SCD) - death due to sudden cardiac arrest or unexpected sudden death; (2) heart failure - death due to refractory heart failure; or (3) stroke - death due to embolic stroke associated with atrial fibrillation. MACEs included: (1) SCD, sudden unexpected aborted cardiac arrest, fatal, or nonfatal ventricular arrhythmia (ventricular fibrillation or sustained ventricular tachycardia); (2) heart failure (fatal or non-fatal), or heart transplantation; or (3) stroke - fatal or non-fatal embolic stroke associated with atrial fibrillation. RESULTS: One hundred and sixty-one Thai patients with HCM (age 66 ± 16 years, 58% female) were enrolled. Forty-two patients (26%) died over a median follow-up period of 6.8 years including 25 patients (16%) with HCM-related deaths (2%/year). The HCM-related deaths included: heart failure (52% of HCM-related deaths; n = 13), SCD (44% of HCM-related deaths; n = 11), and stroke (4% of HCM-related deaths, n = 1). The SCDs occurred in 6.8% of patients (1%/year). Eighty-four major MACEs occurred in 65 patients (41, 5%/year). The MACEs included: 40 heart failures in which 2 patients underwent heart transplants; 22 SCDs and nonfatal ventricular arrhythmias; and 22 fatal or nonfatal strokes. CONCLUSIONS: The most common mode of death in adult patients with HCM in Thailand was heart failure followed by SCD. About one-third of the patients experiencing heart failure died during the 6.8 years of follow-up. SCDs occurred in 7% of patients (1%/year), predominantly in the fourth decade or later.

Contrast-induced nephropathy is associated with new-onset atrial fibrillation in acute coronary syndrome after cardiac catheterization: Systemic review and meta-analysis.

INTRODUCTION: Contrast-induced nephropathy (CIN) is associated with increased cardiovascular morbidity and mortality in patients with acute coronary syndrome (ACS). Recent studies suggest that CIN is associated with new-onset atrial fibrillation (AF) in patients with acute coronary syndrome (ACS) who underwent catheterization. However, a systematic review and meta-analysis of the literature have not been done. We assessed the association between CIN in patients with ACS and new-onset AF by a systematic review of the literature and a meta-analysis. HYPOTHESIS: CIN is associated with new-onset AF in patients with ACS. METHODS: We comprehensively searched the databases of MEDLINE and EMBASE from inception to April 2018. Included studies were published cohort studies that compared new-onset AF after cardiac catheterization in ACS patient with CIN versus without CIN. Data from each study were combined using the random effects, generic inverse variance method of DerSimonian and Laird to calculate risk ratios and 95% confidence intervals. RESULTS: Five studies from December 2009 to February 2018 were included in this meta-analysis involving 5,640 subjects with ACS (1,102 with CIN and 4,538 without CIN). Contrast-induced nephropathy significantly correlates with new-onset AF after cardiac catheterization (pooled risk ratio = 2.84, 95% confidence interval: 1.66-4.87, p < 0.001, I2  = 58%) CONCLUSIONS: Contrast-induced nephropathy is associated with new-onset AF threefold among patients with ACS after cardiac catheterization. Our study warranted further study to establish the causality between CIN and new-onset AF.

The presence of atrial fibrillation in Takotsubo cardiomyopathy is predictive of mortality: Systematic review and meta-analysis.

INTRODUCTION: Atrial fibrillation (AF) is known as the most common arrhythmia and an independent risk factor for mortality. Recent studies suggest that AF is associated with morbidity and mortality in Takotsubo cardiomyopathy (TTC). However, a systematic review and meta-analysis of the literature have not been done. We assessed the association between AF in patients with TTC and mortality by a systematic review of the literature and a meta-analysis. METHODS: We comprehensively searched the databases of MEDLINE and EMBASE from inception to January 2018. Included studies were published prospective or retrospective cohort studies that compared all-cause mortality in TTC with AF versus without AF. Data from each study were combined using the random-effects, generic inverse variance method of DerSimonian and Laird to calculate risk ratios and 95% confidence intervals. RESULTS: Five studies from August 2008 to October 2017 were included in this meta-analysis involving 2,321 subjects with TTC (243 with AF and 2,078 without AF). The presence of AF was associated with all-cause mortality (pooled odds ratio = 2.19, 95% confidence interval: 1.57-3.06, p < 0.001, I 2  = 0%). CONCLUSION: Atrial fibrillation increased all-cause mortality by double among patients with TTC compared to without it. Our study suggests that the presence of AF in TTC is prognostic for all-cause mortality.

Low-dose basiliximab induction therapy in heart transplantation.

We prospectively studied efficacy and safety outcomes of two 10-mg doses of intravenous basiliximab on day 0 and day 4 for induction therapy in 17 consecutive de novo heart transplant recipients. By the 2-week assessment post-transplant, there were no deaths, graft failures, or acute cellular rejections (ACRs) ISHLT grade ≥ 2R. By the 1-year assessment post-transplant, there were 1 (6%) infectious death, no graft failures, 2 (12%) grade 2R ACRs, 6 (35%) asymptomatic cytomegalovirus (CMV) infections, and 4 (25%) treated infections. Our study was the first to show that low-dose basiliximab induction in heart transplant resulted in favorable efficacy and safety outcomes. Additionally, calcineurin inhibitor (CNI) initiation in a low-risk population could be safely delayed using the strategy of modified low-dose postoperative basiliximab. This strategy also appears to allow subsequent early corticosteroid wean, although with the concomitant maintenance of higher CNI levels and higher dosing of mycophenolate.

Understanding the variability in red cell and plasma volume combinations can help guide management in heart failure.

AIMS: Quantitative methods have shown clinically significant heterogeneity in blood volume (BV) profiles across heart failure (HF) phenotypes. These profiles extend from hypovolaemia to normal BV and to variable degrees of BV hypervolaemia, frequently with similar clinical presentations. However, a comprehensive survey of BV profiles providing practical clinical guidance for the interpretation and management of quantitative plasma volume (PV) and red blood cell (RBC) mass findings has not been reported. The intent of this study is to advance this concept through a multicentre analysis. METHODS AND RESULTS: A retrospective analysis of clinical and BV data was undertaken in stable NYHA class II-III HF patients (N = 546). BV was quantitated using established nuclear medicine indicator-dilution methodology. Differing combinations of PV and RBC mass were identified contributing to marked heterogeneity in overall BV profiles. A quantitatively normal BV was identified in 32% of the cohort but of these only ~1/3 demonstrated a true normal BV (i.e., normal PV + normal RBC mass). The remaining portion of normal BV profiles reflected balanced combinations of compensatory PV expansion with RBC mass deficit (anaemia) (14% of cohort) and PV contraction with RBC mass excess (erythrocythemia) (6% of cohort). Main contributors to BV hypervolaemia were PV excess with a normal RBC mass (21% of cohort; 23% female) and PV excess with erythrocythemia (24% of cohort; 26% female). Hypovolaemia was predominately defined by RBC mass deficit with a normal PV (6% of cohort; 57% female) or RBC mass deficit with PV contraction (5% of cohort; 48% female). CONCLUSIONS: Findings support the clinical relevance of identifying and accurately interpreting the varying combinations of PV and RBC mass in patients with chronic HF. This in turn helps guide appropriate individualized patient management strategies. A practical volume-based guideline is provided in an effort to aid clinician interpretation.

Racial Differences in Hospice Care Outcomes in Patients With Advanced Heart Failure: Systematic Review and Meta-analysis.

There remains a paucity of investigational data about disparities in hospice services in people with non-cancer diagnoses, specifically in heart failure (HF). Black patients with advanced HF have been disproportionally affected by health care services inequities but their outcomes after hospice enrollment are not well studied. We aimed to describe race-specific outcomes in patients with advanced HF who were enrolled in hospice services. We obtained the data from PubMed, Scopus, and Embase for all investigations published until January 11, 2023. All studies that reported race-specific outcomes after hospice enrollment in patients with advanced HF were included. Of the 1,151 articles identified, 5 studies (n = 24,899) were considered for analysis involving a sample size ranging from 179 to 11,754 patients. Black patients had an increased risk of readmission (odds ratio 1.55, 95% confidence interval [CI] 1.34 to 1.79, I2 0%) and discharge (odds ratio 1.75, 95% CI 1.53 to 1.99, I2 0%) compared with White patients. Moreover, Black patients have a nonsignificant lower risk of mortality compared with White patients (relative risk 0.67, 95% CI 0.43 to 1.05, I2 90%). In conclusion, this study showed that Black patients with advanced HF receiving hospice care have a higher risk of readmission and discharge compared with White patients.

Genitourinary Tract Infections in Patients Taking SGLT2 Inhibitors: JACC Review Topic of the Week.

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have been shown to reduce adverse cardiovascular events in patients with type 2 diabetes mellitus, all-cause mortality, and heart failure hospitalization in patients with heart failure, as well as adverse renal outcomes. However, concerns regarding the heightened risk of genitourinary (GU) infections, particularly urinary tract infections, remain a significant barrier to their wider adoption. Addressing these misconceptions using existing evidence is needed to ensure proper risk-benefit assessment and optimal utilization of this efficacious therapy. This review aims to provide a balanced perspective on the evidence-based cardiovascular and renal benefits of SGLT2is and the associated risk of GU infections. We also summarize and propose clinical practice considerations for SGLT2i-associated GU infections focusing on patients with cardiovascular disease.

Feasibility of a Novel Augmented 6-Minute Incremental Step Test: A Simplified Cardiorespiratory Fitness Assessment Tool.

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.