Ultrasound Neuromodulation of an Anti-Inflammatory Pathway at the Spleen Improves Experimental Pulmonary Hypertension.

BACKGROUND: Inflammation is pathogenically implicated in pulmonary arterial hypertension; however, it has not been adequately targeted therapeutically. We investigated whether neuromodulation of an anti-inflammatory neuroimmune pathway involving the splenic nerve using noninvasive, focused ultrasound stimulation of the spleen (sFUS) can improve experimental pulmonary hypertension. METHODS: Pulmonary hypertension was induced in rats either by Sugen 5416 (20 mg/kg SQ) injection, followed by 21 (or 35) days of hypoxia (sugen/hypoxia model), or by monocrotaline (60 mg/kg IP) injection (monocrotaline model). Animals were randomized to receive either 12-minute-long sessions of sFUS daily or sham stimulation for 14 days. Catheterizations, echocardiography, indices of autonomic function, lung and heart histology and immunohistochemistry, spleen flow cytometry, and lung single-cell RNA sequencing were performed after treatment to assess the effects of sFUS. RESULTS: Splenic denervation right before induction of pulmonary hypertension results in a more severe disease phenotype. In both sugen/hypoxia and monocrotaline models, sFUS treatment reduces right ventricular systolic pressure by 25% to 30% compared with sham treatment, without affecting systemic pressure, and improves right ventricular function and autonomic indices. sFUS reduces wall thickness, apoptosis, and proliferation in small pulmonary arterioles, suppresses CD3+ and CD68+ cell infiltration in lungs and right ventricular fibrosis and hypertrophy and lowers BNP (brain natriuretic peptide). Beneficial effects persist for weeks after sFUS discontinuation and are more robust with early and longer treatment. Splenic denervation abolishes sFUS therapeutic benefits. sFUS partially normalizes CD68+ and CD8+ T-cell counts in the spleen and downregulates several inflammatory genes and pathways in nonclassical and classical monocytes and macrophages in the lung. Differentially expressed genes in those cell types are significantly enriched for human pulmonary arterial hypertension-associated genes. CONCLUSIONS: sFUS causes dose-dependent, sustained improvement of hemodynamic, autonomic, laboratory, and pathological manifestations in 2 models of experimental pulmonary hypertension. Mechanistically, sFUS normalizes immune cell populations in the spleen and downregulates inflammatory genes and pathways in the lung, many of which are relevant in human disease.

The Tricuspid Valve: A Review of Pathology, Imaging, and Current Treatment Options: A Scientific Statement From the American Heart Association.

Tricuspid valve disease is an often underrecognized clinical problem that is associated with significant morbidity and mortality. Unfortunately, patients will often present late in their disease course with severe right-sided heart failure, pulmonary hypertension, and life-limiting symptoms that have few durable treatment options. Traditionally, the only treatment for tricuspid valve disease has been medical therapy or surgery; however, there have been increasing interest and success with the use of transcatheter tricuspid valve therapies over the past several years to treat patients with previously limited therapeutic options. The tricuspid valve is complex anatomically, lying adjacent to important anatomic structures such as the right coronary artery and the atrioventricular node, and is the passageway for permanent pacemaker leads into the right ventricle. In addition, the mechanism of tricuspid pathology varies widely between patients, which can be due to primary, secondary, or a combination of causes, meaning that it is not possible for 1 type of device to be suitable for treatment of all cases of tricuspid valve disease. To best visualize the pathology, several modalities of advanced cardiac imaging are often required, including transthoracic echocardiography, transesophageal echocardiography, cardiac computed tomography, and cardiac magnetic resonance imaging, to best visualize the pathology. This detailed imaging provides important information for choosing the ideal transcatheter treatment options for patients with tricuspid valve disease, taking into account the need for the lifetime management of the patient. This review highlights the important background, anatomic considerations, therapeutic options, and future directions with regard to treatment of tricuspid valve disease.

Cardiac Resynchronization Therapy Improves Outcomes in Patients With Intraventricular Conduction Delay But Not Right Bundle Branch Block: A Patient-Level Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Benefit from cardiac resynchronization therapy (CRT) varies by QRS characteristics; individual randomized trials are underpowered to assess benefit for relatively small subgroups. METHODS: The authors analyzed patient-level data from pivotal CRT trials (MIRACLE [Multicenter InSync Randomized Clinical Evaluation], MIRACLE-ICD [Multicenter InSync ICD Randomized Clinical Evaluation], MIRACLE-ICD II [Multicenter InSync ICD Randomized Clinical Evaluation II], REVERSE [Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction], RAFT [Resynchronization-Defibrillation for Ambulatory Heart Failure], BLOCK-HF [Biventricular Versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block], COMPANION [Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure], and MADIT-CRT [Multicenter Automatic Defibrillator Implantation Trial - Cardiac Resynchronization Therapy]) using Bayesian Hierarchical Weibull survival regression models to assess CRT benefit by QRS morphology (left bundle branch block [LBBB], n=4549; right bundle branch block [RBBB], n=691; and intraventricular conduction delay [IVCD], n=1024) and duration (with 150-ms partition). The continuous relationship between QRS duration and CRT benefit was also examined within subgroups defined by QRS morphology. The primary end point was time to heart failure hospitalization (HFH) or death; a secondary end point was time to all-cause death. RESULTS: Of 6264 patients included, 25% were women, the median age was 66 [interquartile range, 58 to 73] years, and 61% received CRT (with or without an implantable cardioverter defibrillator). CRT was associated with an overall lower risk of HFH or death (hazard ratio [HR], 0.73 [credible interval (CrI), 0.65 to 0.84]), and in subgroups of patients with QRS ≥150 ms and either LBBB (HR, 0.56 [CrI, 0.48 to 0.66]) or IVCD (HR, 0.59 [CrI, 0.39 to 0.89]), but not RBBB (HR 0.97 [CrI, 0.68 to 1.34]; Pinteraction <0.001). No significant association for CRT with HFH or death was observed when QRS was <150 ms (regardless of QRS morphology) or in the presence of RBBB. Similar relationships were observed for all-cause death. CONCLUSIONS: CRT is associated with reduced HFH or death in patients with QRS ≥150 ms and LBBB or IVCD, but not for those with RBBB. Aggregating RBBB and IVCD into a single "non-LBBB" category when selecting patients for CRT should be reconsidered. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifiers: NCT00271154, NCT00251251, NCT00267098, and NCT00180271.

Has mortality in the United States returned to pre-pandemic levels? An analysis of provisional 2023 data.

BACKGROUND: The COVID-19 pandemic, which started in 2020, resulted in greater all-cause mortality in 2020 and in subsequent years. Whether all-cause mortality remains elevated in 2023 compared to pre-pandemic numbers is unknown. METHODS AND RESULTS: The United States (US) Center for Disease Control Wide-Ranging, Online Data for Epidemiologic Research database was used to compare mortality rates between 2019 and provisional data for 2022 and 2023. Age-adjusted mortality rates (AAMRs) for all-cause as well as top causes of mortality were collected. Mortality based on subgroups by sex, age, and ethnicity was also collected. All-cause AAMRs between 2018 and 2023 per 100,000 individuals were 723.6, 715.2, 835.4, 879.7, (provisionally) 798.8, and (provisionally) 738.3, respectively, with AAMRs in 2023 remaining above 2019 pre-pandemic levels. Similar trends were noted in subgroups based on sex, ethnicity, and most age groups. Mortality attributed directly to COVID-19 peaked in 2021 as the 3rd leading cause of death and dropped to the 10th leading cause in 2023. Provisional mortality rate trends for 2023 suggest that rates for diseases of the heart increased during the pandemic but appear to have returned to or dipped below pre-pandemic levels. CONCLUSION: Provisional 2023 all-cause mortality rates in the US have decreased from the 2021 peak associated with the COVID-19 pandemic but remain above the pre-pandemic baseline. Mortality from some conditions, including diseases of the heart, appears to have recovered from the impact of the COVID-19 pandemic.

Association between atrial fibrillation and heart failure patient reported outcomes across the ejection fraction spectrum.

BACKGROUND: Atrial fibrillation (AF) is common in patients with heart failure (HF) and is associated with worse clinical outcomes. We evaluated the relationship between AF and longitudinal changes in health-related quality of life (HRQoL) measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) in both HF with preserved (HFpEF) and reduced ejection fraction (HFrEF). METHODS: This is a post-hoc analysis of the TOPCAT and HF-ACTION trials. The effect of AF on KCCQ overall summary scores (OSS), in both trials, was examined using a mixed effects regression model. Patients were divided into 3 groups according to AF status at baseline: patients with a history of AF but no AF detected on ECG at enrollment (Hx AF group), patients with history of AF and AF detected on ECG at enrollment (ECG AF group) and patients with post-randomization new-onset AF (New AF group). RESULTS: In TOPCAT, among 1,710 patients with KCCQ data available, AF was associated with a significantly lower KCCQ-OSS (-3.98; 95% CI -7.21: -0.74) at 48 months, with a significant AF status by time interaction (P = .03). In HF-ACTION, among 1,814 patients with available KCCQ data, AF was associated with a significantly lower KCCQ-OSS (-3.67; 95% CI -6.21: -1.41) at 24 months but there was no significant AF status by time interaction. In both trials, the type of AF was not associated with significant changes in KCCQ-OSS score. CONCLUSION: Ιn patients with both HFpEF and HFrEF, AF was independently associated with worse HRQoL measured by KCCQ.

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.

Previous heart failure hospitalization, spironolactone, and outcomes in heart failure with preserved ejection fraction - a secondary analysis of TOPCAT.

BACKGROUND: Hospitalization for heart failure (HHF) is associated with poor postdischarge outcomes but the role of time since most recent HHF and potential treatment interactions are unknown. We aimed to assess history of and time since previous HHF, associations with composite of cardiovascular (CV) death and total HHF, first HHF and interactions with randomization to spironolactone, in heart failure with preserved ejection fraction. METHODS AND RESULTS: We assessed these objectives using uni- and multivariable regressions and spline analyses in TOPCAT-Americas. Among 1,765 patients, 66% had a previous HHF. Over a median of 2.9 years, 1,064 composite events of CV death or total HHFs occurred. Previous HHF was associated with more severe HF, and was independently associated with the composite outcome (HR 1.26, 95%CI 1.05-1.52, P = .014), and all secondary outcomes. A shorter time since most recent HHF appeared to be associated with subsequent first HHF, but not the composite of CV death or total HHF. Spironolactone had a significant interaction with previous HHF (interaction-P .046). Patients without a previous HHF had a larger effect of spironolactone on the composite outcome (HR 0.63, 95%CI 0.46-0.87, P = .005) than patients with a previous HHF (HR 0.91, 95%CI 0.78-1.06, P = .224). CONCLUSION: In TOPCAT-Americas, previous HHF was associated with CV death and first and total HHF. Duration since most recent HHF seemed to be associated with time to first HHF only. Spironolactone was associated with better outcomes in patients without a previous HHF. This interaction is hypothesis-generating and requires validation in future trials.

Association of disproportionate liver fat with markers of heart failure: The multi-ethnic study of atherosclerosis.

BACKGROUND: Metabolic dysfunction associated steatotic liver disease (MASLD) has been linked to heart failure with preserved ejection fraction (HFpEF). We sought to understand association between individuals with amounts of liver adiposity greater than would be predicted by their body mass index (BMI) in order to understand whether this disproportionate liver fat (DLF) represents a proxy of metabolic risk shared between liver and heart disease. METHODS: We studied 2,932 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) who received computed tomography (CT) measurements of hepatic attenuation. Quartiles of DLF were compared and multivariable linear regression was performed to evaluate the association of DLF with clinical, echocardiographic, and quality of life metrics. RESULTS: Compared to the lowest quartile of DLF, individuals in the highest quartile of DLF were more likely to be male (52.0% vs 47.1%, P < .001), less likely to be Black or African American (14.8 % vs 38.1% P < .001), have higher rates of dysglycemia (31.9% vs 16.6%, P < .001) and triglycerides (140 [98.0, 199.0] vs 99.0 [72.0, 144.0] mg/dL, P > .001). These individuals had lower global longitudinal strain (-0.13 [-0.25, -0.02], P = .02), stroke volumes (-1.05 [-1.76, -0.33], P < .01), lateral e' velocity (-0.10 [-0.18, -0.02], P = .02), and 6-minute walk distances (-4.25 [-7.62 to -0.88], P = .01). CONCLUSION: DLF is associated with abnormal metabolic profiles and ventricular functional changes known to be associated with HFpEF and may serve as an early metric to assess for those that may progress to clinical HFpEF.

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.

Association of Sacubitril/Valsartan vs Valsartan With Blood Pressure Changes and Symptomatic Hypotension: the PARAGLIDE-HF Trial.

BACKGROUND: In PARAGLIDE-HF, in patients with ejection fraction (EF) > 40%, stabilized after worsening heart failure (WHF), sacubitril/valsartan led to greater reduction in plasma NT-proBNP levels and was associated with clinical benefit compared to valsartan alone, despite more symptomatic hypotension (SH). Concern about SH may be limiting the use of sacubitril/valsartan in appropriate patients. METHODS: We characterized patients by the occurrence of SH (investigator-reported) after randomization to either sacubitril/valsartan or valsartan. A key trial inclusion criterion was systolic blood pressure (SBP) ≥ 100 mmHg for the preceding 6 hours and no SH. We also compared outcomes based on baseline SBP stratified by the median blood pressure. The primary endpoint was time-averaged proportional change in NT-proBNP levels from baseline through weeks 4 and 8. A secondary hierarchical outcome (win ratio) consisted of: (1) cardiovascular death; (2) hospitalizations due to HF; (3) urgent HF visits; and (4) change in NT-proBNP levels. RESULTS: Among 466 randomized patients, 92 (19.7%) experienced SH (sacubitril/valsartan, n = 56 [24.0%]; valsartan, n = 36 [15.5%]; P = 0.020). The median time to the first SH event was similar between treatment arms (18 days vs 15 days, respectively; P = 0.42) as was the proportion of first SH events classified as serious by investigators. Patients who experienced SH with sacubitril/valsartan were more likely to be white (OR 1.87 [95% CI: 0.31, 11.15]), to have a lower baseline SBP (per 10 mmHg increase, OR 0.68 [95% CI: 0.55, 0.85]), or to have a left ventricular ejection fraction (LVEF) of > 60% (OR 2.21 [95% CI: 1.05, 4.65]). Time-averaged change in NT-proBNP levels did not differ between patients with baseline SBP ≥ 128 mmHg vs SBP < 128 mmHg (interaction, P = 0.43). The composite hierarchical outcome for sacubitril/valsartan in patients with baseline SBP ≥ 128 mmHg had a win ratio of 1.34 ([95% CI: 0.91, 1.99]; P = 0.096) vs SBP < 128 mmHg with a win ratio of 1.09 ([95%CI: 0.73, 1.66]; P = 0 .62; interaction P value = 0.42). CONCLUSION: Among patients with LVEF > 40% stabilized after WHF, incident SH was more common with sacubitril/valsartan compared with valsartan. SH was associated with lower baseline SBP, being white, and having higher LVEF. Treatment benefits with sacubitril/valsartan may be more pronounced in patients with higher baseline SBP and lower LVEF (≤ 60%). (Funded by Novartis Pharmaceutical Corporation; ClinicalTrials.gov number, NCT03988634.).

Endovascular Ablation of the Right Greater Splanchnic Nerve in Heart Failure With Preserved Ejection Fraction: Rationale, Design and Lead-in Phase Results of the REBALANCE-HF Trial.

OBJECTIVE: Splanchnic vasoconstriction augments transfer of blood volume from the abdomen into the thorax, which may increase filling pressures and hemodynamic congestion in patients with noncompliant hearts. Therapeutic interruption of splanchnic nerve activity holds promise to reduce hemodynamic congestion in patients with heart failure with preserved ejection fraction (HFpEF). Here we describe (1) the rationale and design of the first sham-controlled, randomized clinical trial of splanchnic nerve ablation for HFpEF and (2) the 12-month results of the lead-in (open-label) trial's participants. METHODS: REBALANCE-HF is a prospective, multicenter, randomized, double-blinded, sham-controlled clinical trial of endovascular, transcatheter, right-sided greater splanchnic nerve ablation for volume management (SAVM) in patients with HFpEF. The primary objectives are to evaluate the safety and efficacy of SAVM and identify responder characteristics to inform future studies. The trial consists of an open-label lead-in phase followed by the randomized, sham-controlled phase. The primary efficacy endpoint is the reduction in pulmonary capillary wedge pressure (PCWP) at 1-month follow-up compared to baseline during passive leg raise and 20W exercise. Secondary and exploratory endpoints include health status (Kansas City Cardiomyopathy Questionnaire), 6-minute walk test distance, New York Heart Association class, and NTproBNP levels at 3, 6 and 12 months. The primary safety endpoint is device- or procedure-related serious adverse events at the 1-month follow-up. RESULTS: The lead-in phase of the study, which enrolled 26 patients with HFpEF who underwent SAVM, demonstrated favorable safety outcomes and reduction in exercise PCWP at 1 month post-procedure and improvements in all secondary endpoints at 6 and 12 months of follow-up. The randomized phase of the trial (n = 44 SAVM; n = 46 sham) has completed enrollment, and follow-up is ongoing. CONCLUSION: REBALANCE-HF is the first sham-controlled randomized clinical trial of greater splanchnic nerve ablation in HFpEF. Initial 12-month open-label results are promising, and the results of the randomized portion of the trial will inform the design of a future pivotal clinical trial. SAVM may offer a promising therapeutic option for patients with HFpEF. TRIAL REGISTRATION: NCT04592445.

Remote Follow-up in a Heart Failure Pragmatic Trial: Insights From the CONNECT-HF.

BACKGROUND: Randomized controlled trials typically require study-specific visits, which can burden participants and sites. Remote follow-up, such as centralized call centers for participant-reported or site-reported, holds promise for reducing costs and enhancing the pragmatism of trials. In this secondary analysis of the CONNECT-HF (Care Optimization Through Patient and Hospital Engagement For HF) trial, we aimed to evaluate the completeness and validity of the remote follow-up process. METHODS AND RESULTS: The CONNECT-HF trial evaluated the effect of a post-discharge quality-improvement intervention for heart failure compared to usual care for up to 1 year. Suspected events were reported either by participants or by health care proxies through a centralized call center or by sites through medical-record queries. When potential hospitalization events were suspected, additional medical records were collected and adjudicated. Among 5942 potential hospitalizations, 18% were only participant-reported, 28% were reported by both participants and sites, and 50% were only site-reported. Concordance rates between the participant/site reports and adjudication for hospitalization were high: 87% participant-reported, 86% both, and 86% site-reported. Rates of adjudicated heart failure hospitalization events among adjudicated all-cause hospitalization were lower but also consistent: 45% participant-reported, 50% both, and 50% site-reported. CONCLUSIONS: Participant-only and site-only reports missed a substantial number of hospitalization events. We observed similar concordance between participant/site reports and adjudication for hospitalizations. Combining participant-reported and site-reported outcomes data is important to capture and validate hospitalizations effectively in pragmatic heart failure trials.

Blood Pressure Response and Symptoms During Active Standing Test Among Hospitalized and Outpatients With Heart Failure: Results From the GRAVITY-HF Prospective Observational Cohort Study.

BACKGROUND: We conducted a multicenter, prospective, observational study to describe the incidence of orthostatic hypotension (OH) and orthostatic hypertension (OHtn) and its association with symptoms at standing and outcomes in patients with heart failure (HF). METHODS AND RESULTS: 321 active standing tests were performed in 87 inpatients during admission, and 316 tests were performed in 208 outpatients during follow-up. Blood pressure (BP) was measured by an automatic device 4 times in the supine position and at 1, 3 and 5 minutes of standing. Patients were queried about symptoms of orthostatic intolerance. The incidence of OH and OHtn was similar in both groups at baseline (classical OH 11%-22%, OHtn 3%-8%, depending on definition and timing). Reproducibility of BP changes with standing was low. Up to 50% of cases with abnormal responses were asymptomatic. Symptoms were variable and occurred mainly during the first minute of standing and had a U-shaped association with BP changes. OH in outpatients with HF was associated with a higher risks of death or readmission due to HF. CONCLUSIONS: Patients with HF have variable hemodynamic responses and symptoms during repeated active standing tests. OH might identify outpatients with HF who are at risk of long-term negative outcomes.

Novel Trial Designs in Heart Failure: Using Digital Health Tools to Increase Pragmatism.

PURPOSE OF REVIEW: Heart failure is an important clinical and public health issue. There is an urgent need to improve the efficiency of clinical trials in heart failure to rapidly identify new therapies and evidence-based implementation strategies for currently existing therapies. Electronic health (eHealth) platforms and digital health tools are being integrated into heart failure care. In this manuscript, we review opportunities to use these tools to potentially improve the design of and reduce the complexity of clinical trials in heart failure. RECENT FINDINGS: The PRECIS-2 tool outlines clinical trial design domains that are targets for pragmatism. We believe incorporating pragmatic design elements with the aid of eHealth platforms and digital health tools into clinical trials may help address the current complexity of clinical trials in heart failure and improve efficiency. In the manuscript, we provide examples from recent clinical trials across clinical trial design domains. We believe the current adoption of eHealth platforms and digital health tools is an opportunity improve the design of heart failure clinical trials. We specifically believe these tools can enhance pragmatism in clinical trials and reduce delays in generating high-quality evidence for new heart failure therapeutics.

Trends in outcomes and resource utilization for acute myocardial infarction admissions during the COVID-19 pandemic.

During the early COVID-19 pandemic, resources were at times rationed, and as a result, cardiovascular outcomes may have suffered, however despite this, there is a paucity of national data specifically examining the relationship between COVID-19 and acute myocardial infarction (AMI). Some of the most robust previous cohort studies suggest the risk of AMI is increased in patients with COVID-19 infection, and disproportionately so in certain patient populations. To better define national trends in the associations between COVID-19 and AMI, this study aimed to examine demographics, outcomes, and health care utilization in hospitalizations for AMI with a codiagnosis of COVID-19 using a nationally representative database.

Effects of COVID-19 on heart failure admissions.

Despite significant investigation into the effects of COVID-19 on cardiovascular disease, there is a paucity of national data specifically examining its effects on heart failure (HF) hospitalizations. Previous cohort study data demonstrate worsened outcomes in HF patients with recent COVID-19 infection. To better understand this association, this study aimed to utilize a nationally representative database to examine demographics, outcomes, and health care utilization in hospitalizations for HF with a codiagnosis of COVID-19.

Cardiac resynchronization therapy in patients with a prior history of atrial fibrillation: Insights from four major clinical trials.

AIMS: To investigate the association of cardiac resynchronization therapy (CRT) on outcomes among participants with and without a history of atrial fibrillation (AF). METHODS: Individual-patient-data from four randomized trials investigating CRT-Defibrillators (COMPANION, MADIT-CRT, REVERSE) or CRT-Pacemakers (COMPANION, MIRACLE) were analyzed. Outcomes were time to a composite of heart failure hospitalization or all-cause mortality or to all-cause mortality alone. The association of CRT on outcomes for patients with and without a history of AF was assessed using a Bayesian-Weibull survival regression model adjusting for baseline characteristics. RESULTS: Of 3964 patients included, 586 (14.8%) had a history of AF; 2245 (66%) were randomized to CRT. Overall, CRT reduced the risk of the primary composite endpoint (hazard ratio [HR]: 0.69, 95% credible interval [CI]: 0.56-0.81). The effect was similar (posterior probability of no interaction = 0.26) in patients with (HR: 0.78, 95% CI: 0.55-1.10) and without a history of AF (HR: 0.67, 95% CI: 0.55-0.80). In these four trials, CRT did not reduce mortality overall (HR: 0.82, 95% CI: 0.66-1.01) without evidence of interaction (posterior probability of no interaction = 0.14) for patients with (HR: 1.09, 95% CI: 0.70-1.74) or without a history of AF (HR: 0.70, 95% CI: 0.60-0.97). CONCLUSION: The association of CRT on the composite endpoint or mortality was not statistically different for patients with or without a history of AF, but this could reflect inadequate power. Our results call for trials to confirm the benefit of CRT recipients with a history of AF.

Decoupling of Hemodynamics and Congestive Symptoms in Obese Patients With Heart Failure.

BACKGROUND: Prior studies indicate significant physiological differences between obese and nonobese patients with heart failure (HF), but none have evaluated differences in hemodynamic patterns in these patient populations during treatment for acute decompensated HF (ADHF). OBJECTIVES: In this study, we assessed differences in hemodynamic trends between obese and nonobese patients during treatment for ADHF. METHODS: Obese (body mass index (BMI) >30, n = 63) and nonobese (BMI < 25, n = 69) patients with ADHF in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) study who had pulmonary artery catheterization data available through the duration of treatment were evaluated. Hemodynamics were analyzed at baseline and optimal day. Changes in BNP levels, weight, creatinine, BUN, 6MWT, orthopnea and dyspnea scores were assessed. RESULTS: Despite similar baseline hemodynamics, obese patients had significantly less absolute and relative pulmonary arterial wedge pressure (PAWP) reduction (-16 ± 28 vs -32 ± 29%; P = 0.03) during treatment. Obese patients also had higher PAWPs (19.9 + 8 vs 15.5 + 6.8 mmHg; P = 0.01) and PA pressures at optimization compared with nonobese patients. Obese and nonobese patients had similar relative improvements in weight, BNP, 6-minute walk test distance, dyspnea and orthopnea scores, and similar changes in creatinine and BUN levels. CONCLUSIONS: Obese patients treated for ADHF display less reduction in invasively measured left heart filling pressures, despite similar improvements in symptoms, weight loss, and noninvasive surrogates of congestion. Our findings suggest a degree of decoupling between left heart filling pressures and congestive symptoms in obese patients undergoing treatment for ADHF.

Relationship of Vascular Endothelial Growth Factor C, a Lymphangiogenesis Modulator, With Edema Formation, Congestion and Outcomes in Acute Heart Failure.

BACKGROUND: Although vascular endothelial growth factor C (VEGF-C) is a known lymphangiogenesis modulator, its relationship with congestion formation and outcomes in acute heart failure (AHF) is unknown. METHODS: Serum VEGF-C levels were measured in 237 patients hospitalized for AHF. The population was stratified by VEGF-C levels and linked with clinical signs of congestion and outcomes. RESULTS: The study's population was divided in VEGF-C tertiles: low (median [Q25-Q75]: 33 [15-175]), medium (606 [468-741]) and high (1141 [968-1442] pg/mL). The group with low VEGF-C on admission presented with the highest prevalence of severe lower-extremity edema (low VEGF-C vs medium VEGF-C vs high VEGF-C): 30% vs 13% vs 20%; P = 0.02); the highest percentage of patients with ascites: 22% vs 9% vs 6%; P = 0.006; and the lowest proportion of patients with pulmonary congestion: 22% vs 30% vs 46%; P = 0.004. The 1-year mortality rate was the highest in the low VEGF-C tertile: 35% vs 28% vs 18%, respectively; P = 0.049. The same pattern was observed for the composite endpoint (death and AHF rehospitalization): 45% vs 43% vs 26%; P = 0.029. The risks of death at 1-year follow-up and composite endpoint were significantly lower in the high VEGF-C group. CONCLUSIONS: Low VEGF-C was associated with more severe signs of congestion (signs of fluid accumulation) and adverse clinical outcomes.

Association of Hospital Procedural Volume With Outcomes of Left Ventricular Assist Device Placement.

BACKGROUND: With the advancement in device technology, the use of durable left ventricular assist devices (LVADs) has increased significantly in recent years. However, there is a dearth of evidence to conclude whether patients who undergo LVAD implantation at high-volume centers have better clinical outcomes than those receiving care at low- or medium-volume centers. METHODS: We analyzed the hospitalizations using the Nationwide Readmission Database for the year 2019 for new LVAD implantation. Baseline comorbidities and hospital characteristics were compared among low- (1-5 procedures/year), medium- (6-16 procedures/year) and high-volume (17-72 procedures/year) hospitals. The volume/outcome relationship was analyzed using the annualized hospital volume as a categorical variable (tertiles) as well as a continuous variable. Multilevel mixed-effect logistic regression and negative binomial regression models were used to determine the association of hospital volume and outcomes, with tertile 1 (low-volume hospitals) as the reference category. RESULTS: A total of 1533 new LVAD procedures were included in the analysis. The inpatient mortality rate was lower in the high-volume centers compared with the low-volume centers (9.04% vs 18.49%, aOR 0.41, CI0.21-0.80; P = 0.009). There was a trend toward lower mortality rates in medium-volume centers compared with low-volume centers; however, it did not reach statistical significance (13.27% vs 18.49%, aOR 0.57, CI0.27-1.23; P = 0.153). Similar results were seen for major adverse events (composite of stroke/transient ischemic attack and in-hospital mortality). There was no significant difference in bleeding/transfusion, acute kidney injury, vascular complications, pericardial effusion/hemopericardium/tamponade, length of stay, cost, or 30-day readmission rates between medium- and high-volume centers compared to low-volume centers. CONCLUSION: Our findings indicate lower inpatient mortality rates in high-volume LVAD implantation centers and a trend toward lower mortality rates in medium-volume LVAD implantation centers compared to lower-volume centers.