<div><h4>An Economic Modeling Analysis of an Intensive GDMT Optimization Program in Hospitalized Heart Failure Patients.</h4><i>Dixit NM, Parikh NU, Ziaeian B, Fonarow GC</i><br /><AbstractText><b>Background:</b> The STRONG-HF trial demonstrated substantial reductions in the composite of mortality and morbidity over 6 months among hospitalized heart failure patients who were randomized to intensive guideline-directed medical therapy (GDMT) optimization compared to usual care. Whether an intensive GDMT optimization program would be cost-effective for patients with heart failure with reduced ejection fraction (HFrEF) is unknown. <br /><b>Methods:</b><br/>Using a 2-state Markov model we evaluated the effect of an intensive GDMT optimization program on hospitalized patients with HFrEF. Two population models were created to simulate this intervention, a \"Clinical Trial\" model, based off the participants in the STRONG-HF trial and a \"Real-World\" model, based off the Get With The Guidelines-HF Registry of patients admitted with worsening HF. We then modeled the effect of a 6-month intensive triple therapy GDMT optimization program comprised of cardiologists, clinical pharmacists, and registered nurses. Hazard ratios from the intervention arm of the STRONG-HF trial were applied to both populations models to simulate clinical and financial outcomes of an intensive GDMT optimization program from a United States healthcare sector perspective with a lifetime time horizon. Optimal quadruple GDMT use was also modeled. <br /><b>Results:</b><br/>An intensive GDMT optimization program was extremely cost-effective with incremental cost-effectiveness ratios <$10,000 per quality-adjusted life year in both models. Optimal quadruple GDMT implementation resulted in the most gains in life years with incremental cost-effectiveness ratios of $60,000 and $54,000 in the Clinical Trial and Real-World models, respectively. <b>Conclusions:</b> An intensive GDMT optimization program for patients hospitalized with HFrEF would be cost-effective and result in substantial gains in clinical outcomes especially with use of optimal quadruple GDMT. Clinicians, payers, and policy makers should prioritize creation of such programs.</AbstractText><br /><br /><br /><br /><small>Circ Heart Fail: 06 Nov 2023; epub ahead of print</small></div>

<div><h4>Detailed Assessment of the \"I Need Help\" Criteria in Patients With Heart Failure: Insights From the HELP-HF Registry.</h4><i>Pagnesi M, Ghiraldin D, Vizzardi E, Chiarito M, ... Pini D, Metra M</i><br /><b>Background</b><br />The \"I Need Help\" markers have been proposed to identify patients with advanced heart failure (HF). We evaluated the prognostic impact of these markers on clinical outcomes in a real-world, contemporary, multicenter HF population.<br /><b>Methods</b><br />We included consecutive patients with HF and at least 1 high-risk \"I Need Help\" marker from 4 centers. The impact of the cumulative number of \"I Need Help\" criteria and that of each individual \"I Need Help\" criterion was evaluated. The primary end point was the composite of all-cause mortality or first HF hospitalization.<br /><b>Results</b><br />Among 1149 patients enrolled, the majority had 2 (30.9%) or 3 (22.6%) \"I Need Help\" criteria. A higher cumulative number of \"I Need Help\" criteria was independently associated with a higher risk of the primary end point (adjusted hazard ratio for each criterion increase, 1.19 [95% CI, 1.11-1.27]; <i>P</i><0.001), and patients with >5 criteria had the worst prognosis. Need of inotropes, persistently high New York Heart Association classes III and IV or natriuretic peptides, end-organ dysfunction, >1 HF hospitalization in the last year, persisting fluid overload or escalating diuretics, and low blood pressure were the individual criteria independently associated with a higher risk of the primary end point.<br /><b>Conclusions</b><br />In our HF population, a higher number of \"I Need Help\" criteria was associated with a worse prognosis. The individual criteria with an independent impact on mortality or HF hospitalization were need of inotropes, New York Heart Association class or natriuretic peptides, end-organ dysfunction, multiple HF hospitalizations, persisting edema or escalating diuretics, and low blood pressure.<br /><br /><br /><br /><small>Circ Heart Fail: 01 Nov 2023:e011003; epub ahead of print</small></div>

<div><h4>Obesity Modifies Clinical Outcomes of Right Ventricular Dysfunction.</h4><i>Ma JI, Zern EK, Parekh JK, Owunna N, ... Picard MH, Ho JE</i><br /><b>Background</b><br />Right ventricular (RV) dysfunction is associated with increased mortality across a spectrum of cardiovascular diseases. The role of obesity in RV dysfunction and adverse outcomes is unclear.<br /><b>Methods</b><br />We examined patients undergoing right heart catheterization between 2005 and 2016 in a hospital-based cohort. Linear regression was used to examine the association of obesity with hemodynamic indices of RV dysfunction (pulmonary artery pulsatility index, right atrial pressure:pulmonary capillary wedge pressure ratio, RV stroke work index). Cox models were used to examine the association of RV function measures with clinical outcomes.<br /><b>Results</b><br />Among 8285 patients (mean age, 63 years; 40% women), higher body mass index was associated with worse indices of RV dysfunction, including lower pulmonary artery pulsatility index (β, -0.23; SE, 0.01; <i>P</i><0.001), higher right atrium:pulmonary capillary wedge pressure ratio (β, 0.25; SE, 0.01; <i>P</i><0.001), and lower RV stroke work index (β, -0.05; SE, 0.01; <i>P</i><0.001). Over median of 7.3 years of follow-up, we observed 3006 mortality and 2004 heart failure hospitalization events. RV dysfunction was associated with a greater risk of mortality (eg, pulmonary artery pulsatility index:hazard ratio, 1.11 per 1-SD increase [95% CI, 1.04-1.18]), with similar associations with risk of heart failure hospitalization. Body mass index modified the effect of RV dysfunction on all-cause mortality (<i>P</i><sub>interaction</sub>≤0.005 for PAPi and RA:PCWP ratio), such that the effect of RV dysfunction was more pronounced at higher body mass index.<br /><b>Conclusions</b><br />Patients with obesity had worse hemodynamic measured indices of RV function across a broad hospital-based sample. While RV dysfunction was associated with worse clinical outcomes including mortality and heart failure hospitalization, this association was especially pronounced among individuals with higher body mass index.<br /><br /><br /><br /><small>Circ Heart Fail: 27 Oct 2023:e010524; epub ahead of print</small></div>

<div><h4>Efficacy of Dapagliflozin According to Heart Rate: A Patient-Level Pooled Analysis of DAPA-HF and DELIVER.</h4><i>Kondo T, Butt JH, Curtain JP, Jhund PS, ... Solomon SD, McMurray JJV</i><br /><b>Background</b><br />Although elevated resting heart rate (HR) is associated with a higher risk of cardiovascular events in patients with heart failure with reduced ejection fraction in sinus rhythm (SR), the relationship between HR and outcomes among patients with heart failure with mildly reduced ejection fraction/heart failure with preserved ejection fraction and in those with atrial fibrillation (AF) is uncertain. The aims of this study were to examine the association between baseline HR and outcomes across the range of left ventricular ejection fraction, in patients with and without AF, and evaluate the effect of dapagliflozin according to HR.<br /><b>Methods</b><br />A patient-level pooled analysis of the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure; heart failure with reduced ejection fraction) and DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure trial; heart failure with mildly reduced ejection fraction/heart failure with preserved ejection fraction) trials. The primary outcome of each was the composite of worsening heart failure or cardiovascular death.<br /><b>Results</b><br />Among patients with SR (n=6401, 64%), the rate of the primary outcome was higher in those with higher HR: 16.8 versus 7.7 per 100 person-years for ≥80 bpm versus <60 bpm. The relationship between HR and risk was steeper in heart failure with reduced ejection fraction versus heart failure with mildly reduced ejection fraction/heart failure with preserved ejection fraction. HR was not associated with outcomes in patients in AF for either heart failure phenotype. The benefit of dapagliflozin on the primary outcome was consistent across the HR range in both SR (<i>P</i><sub>interaction</sub>=0.28) and AF (<i>P</i><sub>interaction</sub>=0.56), for example, for SR <60 bpm, hazard ratio for dapagliflozin versus placebo 0.72 (95% CI, 0.55-0.95); 60 to 69 bpm, 0.78 (0.63-0.97); 70 to 79 bpm, 0.73 (0.59-0.91); ≥80 bpm, 0.77 (0.61-0.97). The benefit was consistent across HR range in both heart failure with reduced ejection fraction and heart failure with mildly reduced ejection fraction/heart failure with preserved ejection fraction.<br /><b>Conclusions</b><br />The risk of worsening heart failure or cardiovascular death increased with increasing baseline HR among patients in SR, but this association was not seen among patients in AF, irrespective of left ventricular ejection fraction. The benefit of dapagliflozin was consistent across HR range, irrespective of left ventricular ejection fraction or rhythm.<br /><b>Registration</b><br />URL: https://www.<br /><b>Clinicaltrials</b><br />gov; Unique identifier: NCT03036124 and NCT03619213.<br /><br /><br /><br /><small>Circ Heart Fail: 27 Oct 2023:e010898; epub ahead of print</small></div>

<div><h4>Palliative Care for Patients With Heart Failure With Preserved Ejection Fraction.</h4><i>Godfrey S, Peng Y, Lorusso N, Sulistio M, ... Pandey A, Warraich H</i><br /><AbstractText>Heart failure with preserved ejection fraction (HFpEF) has become the leading form of heart failure worldwide, particularly among elderly patient populations. HFpEF is associated with significant morbidity and mortality that may benefit from incorporation of palliative care (PC). Patients with HFpEF have similarly high mortality rates to patients with heart failure with reduced ejection fraction. PC trials for heart failure have shown improvement in quality of life, quality of death, and health care utilization, although most trials defined heart failure clinically without differentiating between HFpEF and heart failure with reduced ejection fraction. As such, the timing and role of PC for HFpEF care remains uncertain, and PC referral rates for HFpEF are very low despite potential improvements in important patient-centered outcomes. Specific barriers to referral include limited data, prognostic uncertainty, provider misconceptions about PC, inadequate specialty PC workforce, complexities of treating multimorbidity, and limited home care options for patients with heart failure. While there are many barriers to integration of PC into HFpEF care, there are multiple potential benefits to patients with HFpEF throughout their disease course. As this population continues to grow, targeted efforts to study and implement PC interventions are needed to improve patient quality of life and death.</AbstractText><br /><br /><br /><br /><small>Circ Heart Fail: 23 Oct 2023:e010802; epub ahead of print</small></div>

<div><h4>Effect of Dapagliflozin on 6-Minute Walk Distance in Heart Failure With Preserved Ejection Fraction: PRESERVED-HF.</h4><i>Lewis GD, Gosch K, Cohen LP, Nassif ME, ... Kosiborod MN, Sauer AJ</i><br /><b>Background</b><br />Heart failure with preserved ejection fraction is associated with significant functional limitations, yet treatments for improving exercise performance have been elusive. We sought to explore the association between prespecified patient characteristics and changes in 6-minute walk distance that constitute a clinically significant response to dapagliflozin.<br /><b>Methods</b><br />We performed a responder analysis to understand patient characteristics associated with clinically meaningful improvement in 6-minute walk test (6MWT) distance ≥15 m among patients randomized to 12 weeks of dapagliflozin versus placebo in the double-blind PRESERVED-HF trial (Effects of Dapagliflozin on Biomarkers, Symptoms and Functional Status in Patients With Preserved Ejection Fraction Heart Failure).<br /><b>Results</b><br />A total of 289 randomized patients had 6MWT distance completed at baseline and 12 weeks. Patients randomized to dapagliflozin improved walking distance by ≥15 m more frequently than those on placebo (n=64, 44% versus n=48, 34%). After adjusting for baseline covariates, patients randomized to dapagliflozin were more likely to experience a clinically meaningful improvement in 6MWT distance compared with those that received placebo (adjusted odds ratio, 1.66 [95% CI, 1.00-2.75]; <i>P</i>=0.05). Dapagliflozin-treated patients were also less likely to have a ≥15 m reduction in 6MWT distance compared with placebo-treated patients (adjusted odds ratio, 0.56 [95% CI, 0.33-0.94]; <i>P</i>=0.03). These results were consistent across all prespecified subgroups (all <i>P</i> values for interaction were not significant).<br /><b>Conclusions</b><br />Compared with those on placebo, patients with heart failure with preserved ejection fraction randomized to dapagliflozin were more likely to experience a clinically meaningful improvement and less likely to experience a deterioration in physical function over 12 weeks as measured by 6MWT distance. Beneficial response to dapagliflozin was consistent across prespecified subgroups.<br /><b>Registration</b><br />URL: https://www.<br /><b>Clinicaltrials</b><br />gov; Unique identifier: PRESERVED-HF NCT03030235.<br /><br /><br /><br /><small>Circ Heart Fail: 23 Oct 2023:e010633; epub ahead of print</small></div>

<div><h4>MMP-2 Associates With Incident Heart Failure and Atrial Fibrillation: The ARIC Study.</h4><i>Buckley LF, Agha AM, Dorbala P, Claggett BL, ... Ballantyne CM, Shah AM</i><br /><b>Background</b><br />MMP (matrix metalloproteinase)-2 participates in extracellular matrix regulation and may be involved in heart failure (HF), atrial fibrillation (AF), and coronary heart disease.<br /><b>Methods</b><br />Among the 4693 ARIC study (Atherosclerosis Risk in Communities) participants (mean age, 75±5 years; 42% women) without prevalent HF, multivariable Cox proportional hazard models were used to estimate associations of plasma MMP-2 levels with incident HF, HF with preserved ejection fraction (≥50%), HF with reduced ejection fraction (<50%), AF, and coronary heart disease. Mediation of the association between MMP-2 and HF was assessed by censoring participants who developed AF or coronary heart disease before HF. Multivariable linear regression models were used to assess associations of MMP-2 with measures of left ventricular and left atrial structure and function.<br /><b>Results</b><br />Compared with the 3 lower quartiles, the highest MMP-2 quartile associated with greater risk of incident HF overall (adjusted hazard ratio, 1.48 [95% CI, 1.21-1.81]), incident HF with preserved ejection fraction (1.44 [95% CI, 1.07-1.94]), incident heart failure with reduced ejection fraction (1.48 [95% CI, 1.08-2.02]), and incident AF (1.44 [95% CI, 1.18-1.77]) but not incident coronary heart disease (0.97 [95% CI, 0.71-1.34]). Censoring AF attenuated the MMP-2 association with HF with preserved ejection fraction. Higher plasma MMP-2 levels were associated with larger left ventricular end-diastolic volume index, greater left ventricular mass index, higher E/e\' ratio, larger left atrial volume index, and worse left atrial reservoir and contractile strains (all <i>P</i><0.001).<br /><b>Conclusions</b><br />Higher plasma MMP-2 levels associate with diastolic dysfunction, left atrial dysfunction, and a higher risk of incident HF and AF. AF is a mediator of MMP-2-associated HF with preserved ejection fraction risk.<br /><br /><br /><br /><small>Circ Heart Fail: 27 Sep 2023:e010849; epub ahead of print</small></div>

<div><h4>Microvascular Dysfunction as a Possible Link Between Heart Failure and Cognitive Dysfunction.</h4><i>Hillier E, Covone J, Fischer K, Chen HY, Hafyane T, Friedrich MG</i><br /><b>Background</b><br />Microvascular function in the brain and heart may play an important role in the course of patients with heart failure (HF), but its relationship with ventricular and cognitive function is not well understood. We hypothesized that microvascular function in HF is closely related to both, cardiac and cognitive function.<br /><b>Methods</b><br />In healthy controls and symptomatic patients with HF (New York Heart Association functional class II or III), we used oxygenation-sensitive magnetic resonance imaging during a standardized breathing maneuver to determine the cerebral oxygenation reserve and the myocardial oxygenation reserve (MORE) as markers for microvascular function. A stepwise multivariable linear regression was performed to determine the variables that best predict changes in cerebral oxygenation reserve and MORE. We also measured cognitive function using the Montreal Cognitive Assessment test.<br /><b>Results</b><br />Twenty patients with HF (age 64.4±8.3 years; 50% female sex), and 21 healthy controls (age 55.0±5.1 years; 62% female sex) were included in the analysis. In patients with HF, cerebral oxygenation reserve and MORE were lower than in healthy controls (MORE, -0.1±3.3 versus 5.0±4.2, cerebral oxygenation reserve: 0.43±0.47 versus 1.21±0.60, respectively) as were Montreal Cognitive Assessment score results (HF, 23.9±3.7; healthy, 27.8±1.5; <i>P</i>=0.002). The Montreal Cognitive Assessment score in patients was correlated with cardiac output (<i>r</i>=0.55, <i>P</i>=0.011) and MORE (<i>r</i>=0.46, <i>P</i>=0.040). In addition to the presence of HF, significant predictors of cerebral and myocardial oxygenation reserve were cardiac output and end-diastolic volume, respectively.<br /><b>Conclusions</b><br />Our results indicate that heart failure is an independent predictor of coronary and cerebral microvascular dysfunction as defined by a reduced response to a vasodilatory breathing maneuver. This impaired response was associated with reduced cognitive function.<br /><br /><br /><br /><small>Circ Heart Fail: 26 Sep 2023:e010117; epub ahead of print</small></div>

<div><h4>Obesity-Related Biomarkers Are Associated With Exercise Intolerance and HFpEF.</h4><i>Ramirez MF, Lau ES, Parekh JK, Pan AS, ... Lewis GD, Ho JE</i><br /><b>Background</b><br />Obesity and adiposity are associated with an increased risk of heart failure with preserved ejection fraction (HFpEF); yet, specific underlying mechanisms remain unclear. We sought to examine the association of obesity-related biomarkers including adipokines (leptin, resistin, adiponectin), inflammatory markers (CRP [C-reactive protein], IL-6 [interleukin-6]), and insulin resistance (HOMA-IR) with HFpEF status, exercise capacity, and cardiovascular outcomes.<br /><b>Methods</b><br />We studied 509 consecutive patients with left ventricular ejection fraction ≥50% and chronic dyspnea, who underwent clinically indicated cardiopulmonary exercise test with invasive hemodynamic monitoring between 2006 and 2017. We defined HFpEF based on the presence of elevated left ventricular filling pressures at rest or during exercise. Fasting blood samples collected at the time of the cardiopulmonary exercise test were used to assay obesity-related biomarkers. We examined the association of log-transformed biomarkers with HFpEF status and exercise traits using multivariable-adjusted logistic regression models.<br /><b>Results</b><br />We observed associations of obesity-related biomarkers with measures of impaired exercise capacity including peak VO<sub>2</sub> (<i>P</i>≤0.002 for all biomarkers). The largest effect size was seen with leptin, where a 1-SD higher leptin was associated with a 2.35 mL/kg per min lower peak VO<sub>2</sub> (β, -2.35±0.19; <i>P</i><0.001). In addition, specific biomarkers were associated with distinct measures of exercise reserve including blood pressure (homeostatic model assessment of insulin resistance, leptin, adiponectin; <i>P</i>≤0.002 for all), and chronotropic response (CRP, IL-6, homeostatic model assessment of insulin resistance, leptin, and resistin; <i>P</i><0.05 for all). Our findings suggest that among the obesity-related biomarkers studied, higher levels of leptin and CRP are independently associated with increased odds of HFpEF, with odds ratios of 1.36 (95% CI, 1.09-1.70) and 1.25 (95% CI, 1.03-1.52), respectively.<br /><b>Conclusions</b><br />Specific obesity-related pathways including inflammation, adipokine signaling, and insulin resistance may underlie the association of obesity with HFpEF and exercise intolerance.<br /><br /><br /><br /><small>Circ Heart Fail: 13 Sep 2023:e010618; epub ahead of print</small></div>

<div><h4>Long-Term Effects of Pulmonary Endarterectomy on Right Ventricular Stiffness and Fibrosis in Chronic Thromboembolic Pulmonary Hypertension.</h4><i>Braams NJ, Kianzad A, van Wezenbeek J, Wessels JN, ... Bogaard HJ, Meijboom LJ</i><br /><b>Background</b><br />Surgical removal of thromboembolic material by pulmonary endarterectomy (PEA) leads within months to the improvement of right ventricular (RV) function in the majority of patients with chronic thromboembolic pulmonary hypertension. However, RV mass does not always normalize. It is unknown whether incomplete reversal of RV remodeling results from extracellular matrix expansion (diffuse interstitial fibrosis) or cellular hypertrophy, and whether residual RV remodeling relates to altered diastolic function.<br /><b>Methods</b><br />We prospectively included 25 patients with chronic thromboembolic pulmonary hypertension treated with PEA. Structured follow-up measurements were performed before, and 6 and 18 months after PEA. With single beat pressure-volume loop analyses, we determined RV end-systolic elastance (Ees), arterial elastance (Ea), RV-arterial coupling (Ees/Ea), and RV end-diastolic elastance (stiffness, Eed). The extracellular volume fraction of the RV free wall was measured by cardiac magnetic resonance imaging and used to separate the myocardium into cellular and matrix volume. Circulating collagen biomarkers were analyzed to determine the contribution of collagen metabolism.<br /><b>Results</b><br />RV mass significantly decreased from 43±15 to 27±11g/m<sup>2</sup> (-15.9 g/m<sup>2</sup> [95% CI, -21.4 to -10.5]; <i>P</i><0.0001) 6 months after PEA but did not normalize (28±9 versus 22±6 g/m<sup>2</sup> in healthy controls [95% CI, 2.1 to 9.8]; <i>P</i><0.01). On the contrary, Eed normalized after PEA. Extracellular volume fraction in the right ventricular free wall increased after PEA from 31.0±3.8 to 33.6±3.5% (3.6% [95% CI, 1.2-6.1]; <i>P</i>=0.013) as a result of a larger reduction in cellular volume than in matrix volume (<i>P</i><sub>interaction</sub>=0.0013). Levels of MMP-1 (matrix metalloproteinase-1), TIMP-1 (tissue inhibitor of metalloproteinase-1), and TGF-β (transforming growth factor-β) were elevated at baseline and remained elevated post-PEA.<br /><b>Conclusions</b><br />Although cellular hypertrophy regresses and diastolic stiffness normalizes after PEA, a relative increase in extracellular volume remains. Incomplete regression of diffuse RV interstitial fibrosis after PEA is accompanied by elevated levels of circulating collagen biomarkers, suggestive of active collagen turnover.<br /><br /><br /><br /><small>Circ Heart Fail: 07 Sep 2023:e010336; epub ahead of print</small></div>

<div><h4>Classification and Predictors of Right Ventricular Functional Recovery in Pulmonary Arterial Hypertension.</h4><i>Rischard FP, Bernardo RJ, Vanderpool RR, Kwon DH, ... Tang WHW, Wilcox JD</i><br /><b>Background</b><br />Normative changes in right ventricular (RV) structure and function have not been characterized in the context of treatment-associated functional recovery (RV functional recovery [RVFnRec]). The aim of this study is to assess the clinical relevance of a proposed RVFnRec definition.<br /><b>Methods</b><br />We evaluated 63 incident patients with pulmonary arterial hypertension by right heart catheterization and cardiac magnetic resonance imaging at diagnosis and cardiac magnetic resonance imaging and invasive cardiopulmonary exercise testing following treatment (≈11 months). Sex, age, ethnicity matched healthy control subjects (n=62) with 1-time cardiac magnetic resonance imaging and noninvasive cardiopulmonary exercise testing were recruited from the PVDOMICS (Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics) project. We examined therapeutic cardiac magnetic resonance imaging changes relative to the evidence-based peak oxygen consumption (VO<sub>2peak</sub>)>15 mL/(kg·min) to define RVFnRec by receiver operating curve analysis. Afterload was measured as mean pulmonary artery pressure, resistance, compliance, and elastance.<br /><b>Results</b><br />A drop in RV end-diastolic volume of -15 mL best defined RVFnRec (area under the curve, 0.87; <i>P</i>=0.0001) and neared upper 95% CI RV end-diastolic volume of controls. This cutoff was met by 22 out of 63 (35%) patients which was reinforced by freedom from clinical worsening, RVFnRec 1 out of 21 (5%) versus no RVFnRec 17 out of 42, 40% (log-rank <i>P</i>=0.006). A therapy-associated increase of 0.8 mL/mm Hg in compliance had the best predictive value of RVFnRec (area under the curve, 0.76; [95% CI, 0.64-0.88]; <i>P</i>=0.001). RVFnRec patients had greater increases in stroke volume, and cardiac output at exercise.<br /><b>Conclusions</b><br />RVFnRec defined by RV end-diastolic volume therapeutic decrease of -15 mL predicts exercise capacity, freedom from clinical worsening, and nears normalization. A therapeutic improvement of compliance is superior to other measures of afterload in predicting RVFnRec. RVFnRec is also associated with increased RV output reserve at exercise.<br /><br /><br /><br /><small>Circ Heart Fail: 04 Sep 2023:e010555; epub ahead of print</small></div>

<div><h4>Common Variants on Increase Hazard of Mortality or Rehospitalization in Patients With Heart Failure From the ASCEND-HF Trial.</h4><i>Gui H, Tang WHW, Francke S, Li J, ... Williams LK, Lanfear DE</i><br /><b>Background</b><br />Heart failure remains a global health burden, and patients hospitalized are particularly at risk, but genetic associates for subsequent death or rehospitalization are still lacking.<br /><b>Methods</b><br />The genetic substudy of the ASCEND-HF trial (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) was used to perform genome-wide association study and transethnic meta-analysis. The overall trial included the patients of self-reported European ancestry (n=2173) and African ancestry (n=507). The end point was death or heart failure rehospitalization within 180 days. Cox models adjusted for 11 a priori predictors of rehospitalization and 5 genetic principal components were used to test the association between single-nucleotide polymorphisms and outcome. Summary statistics from the 2 populations were combined via meta-analysis with the significance threshold considered <i>P</i><5×10<sup>-</sup><sup>8</sup>.<br /><b>Results</b><br />Common variants (rs2342882 and rs35850039 in complete linkage disequilibrium) located in <i>FGD5</i> were significantly associated with the primary outcome in both ancestry groups (European Americans: hazard ratio [HR], 1.38; <i>P</i>=2.42×10<sup>-6</sup>; African ancestry: HR, 1.51; <i>P</i>=4.43×10<sup>-</sup><sup>3</sup>; HR in meta-analysis, 1.41; <i>P</i>=4.25×10<sup>-8</sup>). <i>FGD5</i> encodes a regulator of VEGF (vascular endothelial growth factor)-mediated angiogenesis, and in silico investigation revealed several previous genome-wide association study hits in this gene, among which rs748431 was associated with our outcome (HR, 1.20; meta <i>P</i><0.01). Sensitivity analysis proved <i>FGD5</i> common variants survival association did not appear to operate via coronary artery disease or nesiritide treatment (<i>P</i>>0.05); and the signal was still significant when changing the censoring time from 180 to 30 days (HR, 1.39; <i>P</i>=1.59×10<sup>-5</sup>).<br /><b>Conclusions</b><br />In this multiethnic genome-wide association study of ASCEND-HF, single-nucleotide polymorphisms in <i>FGD5</i> were associated with increased risk of death or rehospitalization. Additional investigation is required to examine biological mechanisms and whether <i>FGD5</i> could be a therapeutic target.<br /><b>Registration</b><br />URL: https://www.<br /><b>Clinicaltrials</b><br />gov; Unique identifier: NCT00475852.<br /><br /><br /><br /><small>Circ Heart Fail: 01 Sep 2023; 16:e010438</small></div>

<div><h4>Hospital at Home as a Treatment Strategy for Worsening Heart Failure.</h4><i>Haywood HB, Fonarow GC, Khan MS, Van Spall HGC, ... Butler J, Greene SJ</i><br /><AbstractText>Hospital at home (HaH) is an innovative care model that may be particularly suited for heart failure (HF). Outpatient visits and inpatient care have been the 2 traditional settings for HF care, yet may not match the social and medical needs of patients at all times. Alternative models such as HaH may represent an effective and patient-centered option for select patients with worsening HF. To date, limited research in HF and other disease states has supported HaH as being safe and lower cost than traditional inpatient admission. Supporting HaH are new payment structures, such as Medicare\'s Acute Hospital Care at Home waiver program. In combination with outpatient visits, outpatient intravenous diuretic clinics, inpatient care, and cardiac intensive care, HaH could be a core component of a comprehensive care model with the potential to match resource utilization with the needs of patients across the spectrum of HF severity, and improve patient outcomes.</AbstractText><br /><br /><br /><br /><small>Circ Heart Fail: 30 Aug 2023:e010456; epub ahead of print</small></div>

<div><h4>Modulation of Pulsatile Left Ventricular Afterload by Renal Denervation in Heart Failure With Preserved Ejection Fraction.</h4><i>Rommel KP, Pagoulatou S, Kresoja KP, Rosch S, ... Stergiopulos N, Lurz P</i><br /><b>Background</b><br />Arterial stiffening contributes to hemodynamic derangements in heart failure with preserved ejection fraction (HFpEF). We sought to investigate the impact of renal denervation on pulsatile left ventricular loading in patients with HFpEF and hypertensive patients without heart failure (control).<br /><b>Methods</b><br />Patients underwent renal denervation for treatment of hypertension and were followed up at 3 months at a single center. A validated computer model of the arterial tree, noninvasive aortic flow curves, left ventricular volumes, and E/e\' as inputs were used to determine key parameters of left ventricular vascular load.<br /><b>Results</b><br />In comparison to controls (n=30), patients with HFpEF (n=30) demonstrated lower total arterial compliance (mean difference, -0.41 [95% CI, -0.72 to -0.10] mL/mm Hg), higher impedance of the proximal aorta (Zc: 0.02; 0.01 to 0.04 mHg·s/mL), premature wave reflections (shorter backward wave transit time normalized to ejection time: -3.5; -6.5% to -0.5%), and higher wave reflection magnitude (reflection coefficient: 7.3; 2.8% to 11.9%). Overall, daytime systolic (-9.2; -12.2 to -6.2 mm Hg) and diastolic blood pressures (-5.9; -7.6 to -4.1 mm Hg) as well as blood pressure variability (-2.0; -3.0 to -0.9 mm Hg) decreased after renal denervation. In patients with HFpEF, total arterial compliance (0.42; 0.17 to 0.67 mL/mm Hg) and backward transit time normalized to ejection time (1.7; 0.4% to 3.0%) increased; Zc (-0.01; -0.02 to -0.01 mm Hg·s/mL) and reflection coefficient (-2.6; -5.0% to -0.3%) decreased after renal denervation. This was accompanied by a symptomatic improvement in patients with HFpEF.<br /><b>Conclusion</b><br />HFpEF is characterized by heightened aortic stiffness and unfavorable pulsatile left ventricular load. These abnormalities are partly normalized after renal denervation.<br /><br /><br /><br /><small>Circ Heart Fail: 30 Aug 2023:e010543; epub ahead of print</small></div>