Journal: Circ Heart Fail

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<div><h4>Epidemiology and Outcomes of Aortic Stenosis in Acute Decompensated Heart Failure: The ARIC Study.</h4><i>Sivaraj K, Arora S, Hendrickson M, Slehria T, ... Rosamond W, Vavalle JP</i><br /><b>Background</b><br />Few studies characterize the epidemiology and outcomes of aortic stenosis (AS) in acute decompensated heart failure (ADHF). This study investigates the significance of AS in contemporary patients who have experienced an ADHF hospitalization.<br /><b>Methods</b><br />The ARIC study (Atherosclerosis Risk in Communities) surveilled ADHF hospitalizations for residents ≥55 years of age in 4 US communities. ADHF cases were stratified by left ventricular ejection fraction (LVEF). Demographic differences in AS burden and the association of varying AS severities with mortality were estimated using multivariable logistic regression.<br /><b>Results</b><br />From 2005 through 2014, there were 3597 (weighted n=16 692) ADHF hospitalizations of which 48.6% had an LVEF <50% and 51.4% an LVEF ≥50%. AS prevalence was 12.1% and 18.7% in those with an LVEF <50% and ≥50%, respectively. AS was less likely in Black than White patients regardless of LVEF: LVEF <50% (odds ratio [OR], 0.34 [95% CI, 0.28-0.42]); LVEF ≥50% (OR, 0.51 [95% CI, 0.44-0.59]). Higher AS severity was independently associated with 1-year mortality in both LVEF subgroups: LVEF <50% (OR, 1.16 [95% CI, 1.04-1.28]); LVEF ≥50% (OR, 1.40 [95% CI, 1.28-1.54]). Sensitivity analyses excluding severe AS patients detected that mild/moderate AS was independently associated with 1-year mortality in both LVEF subgroups: LVEF <50% (OR, 1.23 [95% CI, 1.02-1.47]); LVEF ≥50% (OR, 1.31 [95% CI, 1.14-1.51]).<br /><b>Conclusions</b><br />Among patients who have experienced an ADHF hospitalization, AS is prevalent and portends poor mortality outcomes. Notably, mild/moderate AS is independently associated with 1-year mortality in this high-risk population.<br /><br /><br /><br /><small>Circ Heart Fail: 03 Feb 2023:e009653; epub ahead of print</small></div>
Sivaraj K, Arora S, Hendrickson M, Slehria T, ... Rosamond W, Vavalle JP
Circ Heart Fail: 03 Feb 2023:e009653; epub ahead of print | PMID: 36734224
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<div><h4>Improvement in Renal Function During the Treatment of Acute Decompensated Heart Failure: Relationship With Markers of Renal Tubular Injury and Prognostic Importance.</h4><i>Natov PS, Ivey-Miranda JB, Cox ZL, Moreno-Villagomez J, ... Rao VS, Testani JM</i><br /><b>Background</b><br />Improvement in renal function (IRF) in acute decompensated heart failure is associated with adverse outcomes. The mechanisms driving this paradox remain undefined.<br /><b>Methods</b><br />Using the ROSE-AHF study (Renal Optimization Strategies Evaluation-Acute Heart Failure), 277 patients were grouped according to renal function, with IRF defined by a ≥20% increase (N=75), worsening renal function by a ≥20% decline (N=53), and stable renal function (SRF) by a <20% change (N=149) in estimated glomerular filtration rate between baseline and 72 hours. Three well-validated renal tubular injury markers, NGAL (neutrophil gelatinase-associated lipocalin), NAG (N-acetyl-β-d-glucosaminidase), and KIM-1 (kidney injury molecule 1), were evaluated at baseline and 72 hours. Patients were also classified by the pattern of change in these markers.<br /><b>Results</b><br />Patients with IRF had the lowest admission estimated glomerular filtration rate (IRF, 37 [28 to 51] mL/min per 1.73 m<sup>2</sup>; worsening renal function, 43 [35 to 55] mL/min per 1.73 m<sup>2</sup>; and SRF, 43 [32 to 55] mL/min per 1.73 m<sup>2</sup>; <i>P</i><sub>trend</sub>=0.032) but greater cumulative urine output (IRF, 8780 [7025 to 11 208] mL; worsening renal function, 7860 [5555 to 9765] mL; and SRF, 8150 [6325 to 10 456] mL; <i>P</i><sub>trend</sub>=0.024) and weight loss (IRF, -9.0 [-12.4 to -5.3] lb; worsening renal function, -5.1 [-8.1 to -1.3] lb; and SRF, -7.1 [-11.9 to -3.2] lb; <i>P</i><sub>trend</sub><0.001) despite similar diuretic doses (<i>P</i><sub>trend</sub>=0.16). There were no differences in the relative change in NGAL, NAG, or KIM-1 between renal function groups (<i>P</i><sub>trend</sub>>0.19 for all). Patients with IRF had worse survival than patients with SRF (27% versus 54%; hazard ratio, 1.98 [1.10-3.58]; <i>P</i>=0.024).<br /><b>Conclusions</b><br />IRF during decongestive therapy for acute decompensated heart failure was not associated with improved markers of renal tubular injury and was associated with worsened survival, likely driven by the presence of greater underlying cardiorenal dysfunction and more severe congestion.<br /><br /><br /><br /><small>Circ Heart Fail: 26 Jan 2023:e009776; epub ahead of print</small></div>
Natov PS, Ivey-Miranda JB, Cox ZL, Moreno-Villagomez J, ... Rao VS, Testani JM
Circ Heart Fail: 26 Jan 2023:e009776; epub ahead of print | PMID: 36700431
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<div><h4>Hemodynamic Profiling and Prognosis in Cardiac Amyloidosis.</h4><i>Martens P, Bhattacharya S, Longinow J, Ives L, ... Hanna M, Tang WHW</i><br /><b>Background</b><br />Little information is available on the prognostic relevance of cardiac hemodynamic cutoffs in cardiac amyloidosis (CA) and its subtypes.<br /><b>Methods</b><br />Consecutive patients diagnose with light chain-CA or transthyretin CA undergoing right heart catheterization were analyzed. Prognostic relevance of classic hemodynamic cutoffs of cardiac index (CI <2.2 L/min per m<sup>2</sup>), pulmonary capillary wedge pressure (>18 mm Hg), right atrial pressure (>8 mm Hg), and mean pulmonary artery pressure (≥25 mm Hg or pulmonary hypertension) with the combined end point of cardiac transplant/left ventricular assist device and death and heart failure admissions separately was assessed.<br /><b>Results</b><br />A total of 469 CA patients underwent right heart catheterization (light chain CA=42% and transthyretin CA=52%) of whom 69%, 64%, and 79% had elevated right atrial pressure, pulmonary capillary wedge pressure, and pulmonary hypertension, respectively. The classic hemodynamic cutoffs for right atrial pressure (hazard ratio, 1.26 [0.98-1.62]) and mean pulmonary artery pressure (hazard ratio, 1.28 [0.96-1.71]) did not identify patients at higher risk for adverse outcome; however, cutoffs of 14 mm Hg for right atrial pressure (hazard ratio, 1.59 [1.26-2.00]) and 35 mm Hg for mean pulmonary artery pressure (hazard ratio, 1.30 [1.01-1.66]) performed better to detect worse outcome (<i>P</i><0.05 for both). Reduced CI occurred in 55% of patients and was the strongest variable associated with the risk for cardiac transplant/left ventricular assist device and death, heart failure admissions, and reduced functional capacity. Reduced CI independently predicted risk on top of the Mayo-score in light chain CA and National Amyloid Center score in transthyretin CA (<i>P</i><0.05 for both). Patients with light chain CA had higher pulmonary capillary wedge pressure and lower stroke volume index but maintained CI through a higher heart rate.<br /><b>Conclusions</b><br />Hemodynamic variables are grossly abnormal in CA, but elevated filling pressures are prognostic at significantly higher threshold values than classic cutoff values. CI is the hemodynamic variable most strongly associated with outcome and functionality in CA.<br /><br /><br /><br /><small>Circ Heart Fail: 25 Jan 2023:e010078; epub ahead of print</small></div>
Martens P, Bhattacharya S, Longinow J, Ives L, ... Hanna M, Tang WHW
Circ Heart Fail: 25 Jan 2023:e010078; epub ahead of print | PMID: 36695180
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<div><h4>Mechanical Dyssynchrony of Isolated Left and Right Ventricular Human Myocardium in End-Stage Heart Failure.</h4><i>Mashali MA, Saad NS, Peczkowski KK, Fanning T, ... Mokadam NA, Janssen PML</i><br /><b>Background</b><br />The left and right ventricles of the human heart differ in embryology, shape, thickness, and function. Ventricular dyssynchrony often occurs in cases of heart failure. Our objectives were to assess whether differences in contractile properties exist between the left and right ventricles and to evaluate signs of left/right ventricular mechanical synchrony in isolated healthy and diseased human myocardium.<br /><b>Methods</b><br />Myocardial left and right ventricular trabeculae were dissected from nonfailing and end-stage failing human hearts. Baseline contractile force and contraction/relaxation kinetics of the left ventricle were compared to those of the right ventricle in the nonfailing group (n=41) and in the failing group (n=29). Correlation analysis was performed to assess the mechanical synchrony between left and right ventricular myocardium isolated from the same heart, in nonfailing (n=41) and failing hearts (n=29).<br /><b>Results</b><br />The failing right ventricular myocardium showed significantly higher developed force (Fdev; <i>P</i>=0.001; d=0.98), prolonged time to peak (<i>P</i><0.001; d=1.14), and higher rate of force development (<i>P</i>=0.002; d=0.89) and force decline (<i>P</i>=0.003; d=0.82) compared to corresponding left ventricular myocardium. In healthy myocardium, a strong positive relationship was present between the left and right ventricles in time to peak (r=0.58, <i>P</i><0.001) and maximal kinetic rate of contraction (r=0.63, <i>P</i><0.001). These coefficients were much weaker, often nearly absent, in failing myocardium.<br /><b>Conclusions</b><br />At the level of isolated cardiac trabeculae, contractile performance, specifically of contractile kinetics, is correlated in the nonfailing myocardium between the left and right ventricles\' but this correlation is significantly weaker, or even absent, in end-stage heart failure, suggesting an interventricular mechanical dyssynchrony.<br /><br /><br /><br /><small>Circ Heart Fail: 25 Jan 2023:e009871; epub ahead of print</small></div>
Mashali MA, Saad NS, Peczkowski KK, Fanning T, ... Mokadam NA, Janssen PML
Circ Heart Fail: 25 Jan 2023:e009871; epub ahead of print | PMID: 36695183
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<div><h4>Predictive Modeling to Assess Pretest Probability of Transthyretin Gene Variants Based on Demographic Information.</h4><i>Saef J, Martyn T, Ives L, Roth LR, ... Hanna M, Tang WHW</i><br /><b>Background</b><br />Transthyretin amyloid cardiomyopathy (ATTR-CM) is a morbid condition, though recent advances in diagnosis and therapy stand to change its natural history. Patients\' <i>TTR</i> genotype may guide family screening as more treatments and preventive strategies become available. An efficient, intuitive means of determining pretest genetic risk may better inform patients/clinicians when pursuing genetic testing.<br /><b>Methods</b><br />This is a cohort study of 767 consecutive patients diagnosed with ATTR-CM who underwent genetic testing. Classification and regression trees (CART) analysis created a decision tree assessing likelihood of carrying a pathologic <i>TTR</i> gene variant. Age, sex, and race were used as independent variables. Logistic regression was also performed to model probability of pathologic <i>TTR</i> genotype. The primary outcome was the decision tree\'s accuracy in 2 separate institutions\' ATTR-CM registry.<br /><b>Results</b><br />In our study cohort, 208 patients (27.1%) had ATTRv. Race has served most efficiently as the root node followed by age and sex in a CART algorithm, and showed 88.2% accuracy (75.3% sensitivity, 93.9% specificity) in the validation cohort. The odds of having a <i>TTR</i> gene variant were greater in Black patients compared with non-Black patients (OR, 34.6 [95% CI, 20.5-58.3]; <i>P</i><0.001). Non-Black patients with ATTR-CM aged 69 years and older had <4% risk of having a predisposing mutation.<br /><b>Conclusions</b><br />This CART algorithm incorporating age, sex, and race was able to determine which patients with ATTR-CM have pathogenic <i>TTR</i> mutations with high specificity. Non-Black patients diagnosed at age 69 years or older with ATTR-CM have a low likelihood to have ATTRv.<br /><br /><br /><br /><small>Circ Heart Fail: 20 Jan 2023:e009908; epub ahead of print</small></div>
Saef J, Martyn T, Ives L, Roth LR, ... Hanna M, Tang WHW
Circ Heart Fail: 20 Jan 2023:e009908; epub ahead of print | PMID: 36661045
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<div><h4>Baseline Characteristics of Pediatric Patients With Heart Failure Due to Systemic Left Ventricular Systolic Dysfunction in the PANORAMA-HF Trial.</h4><i>Shaddy R, Burch M, Kantor PF, Solar-Yohay S, ... Kocun M, Bonnet D</i><br /><b>Background</b><br />Sacubitril/valsartan has been approved for the management of heart failure (HF) with reduced ejection fraction in adults. PANORAMA-HF trial (Prospective Trial to Assess the Angiotensin Receptor Blocker Neprilysin Inhibitor LCZ696 Versus Angiotensin-Converting Enzyme Inhibitor for the Medical Treatment of Pediatric HF) investigated its effects on clinical outcomes in pediatric patients with HF.<br /><b>Methods</b><br />PANORAMA-HF is a multicenter, Phase II/III study using an adaptive, seamless, 2-part design. The study aimed to evaluate the pharmacokinetics and pharmacodynamics of single doses of sacubitril/valsartan (Part 1), and the efficacy and safety of sacubitril/valsartan versus enalapril administered twice daily for 52 weeks (Part 2) in pediatric patients with HF due to left ventricular systolic dysfunction with biventricular heart physiology. An innovative trial design using a novel global rank assessment of severity was employed. For analysis, eligible patients were stratified into 3 age groups (Group 1, 6 to <18 years; Group 2a, 2 to <6 years; and Group 3a, 1 month to <2 years) and functional classification (New York Heart Association/Ross class I/II and III/IV).<br /><b>Results</b><br />We report the key demographic, baseline, and clinical characteristics of 375 pediatric patients randomized to receive the study medication. The mean age for patients in Groups 1, 2a, and 3a was 12.2, 3.2, and 1.3 years, respectively. About 70% of patients had a prior HF hospitalization, 85% had New York Heart Association/Ross class I/II HF, and ≈8% were angiotensin-converting enzyme inhibitor/angiotensin receptor blocker naïve.<br /><b>Conclusions</b><br />Compared to other pediatric HF studies, PANORAMA-HF recruited a relatively homogeneous pediatric HF population across 3 age groups, enabling a more robust evaluation of pharmacokinetics/pharmacodynamics and efficacy/safety of sacubitril/valsartan. Most patients had mildly symptomatic HF at baseline.<br /><b>Registration</b><br />URL: https://www.<br /><b>Clinicaltrials</b><br />gov; Unique identifier: NCT02678312.<br /><br /><br /><br /><small>Circ Heart Fail: 05 Jan 2023:e009816; epub ahead of print</small></div>
Shaddy R, Burch M, Kantor PF, Solar-Yohay S, ... Kocun M, Bonnet D
Circ Heart Fail: 05 Jan 2023:e009816; epub ahead of print | PMID: 36601956
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<div><h4>Gut Microbiota-Generated Phenylacetylglutamine and Heart Failure.</h4><i>Romano KA, Nemet I, Prasad Saha P, Haghikia A, ... Van Wagoner DR, Hazen SL</i><br /><b>Background</b><br />The gut microbiota-dependent metabolite phenylacetylgutamine (PAGln) is both associated with atherothrombotic heart disease in humans, and mechanistically linked to cardiovascular disease pathogenesis in animal models via modulation of adrenergic receptor signaling.<br /><b>Methods</b><br />Here we examined both clinical and mechanistic relationships between PAGln and heart failure (HF). First, we examined associations among plasma levels of PAGln and HF, left ventricular ejection fraction, and N-terminal pro-B-type natriuretic peptide in 2 independent clinical cohorts of subjects undergoing coronary angiography in tertiary referral centers (an initial discovery US Cohort, n=3256; and a validation European Cohort, n=829). Then, the impact of PAGln on cardiovascular phenotypes relevant to HF in cultured cardiomyoblasts, and in vivo were also examined.<br /><b>Results</b><br />Circulating PAGln levels were dose-dependently associated with HF presence and indices of severity (reduced ventricular ejection fraction, elevated N-terminal pro-B-type natriuretic peptide) independent of traditional risk factors and renal function in both cohorts. Beyond these clinical associations, mechanistic studies showed both PAGln and its murine counterpart, phenylacetylglycine, directly fostered HF-relevant phenotypes, including decreased cardiomyocyte sarcomere contraction, and B-type natriuretic peptide gene expression in both cultured cardiomyoblasts and murine atrial tissue.<br /><b>Conclusions</b><br />The present study reveals the gut microbial metabolite PAGln is clinically and mechanistically linked to HF presence and severity. Modulating the gut microbiome, in general, and PAGln production, in particular, may represent a potential therapeutic target for modulating HF.<br /><b>Registration</b><br />URL: https://clinicaltrials.gov/; Unique identifier: NCT00590200 and URL: https://drks.de/drks_web/; Unique identifier: DRKS00020915.<br /><br /><br /><br /><small>Circ Heart Fail: 16 Dec 2022:e009972; epub ahead of print</small></div>
Romano KA, Nemet I, Prasad Saha P, Haghikia A, ... Van Wagoner DR, Hazen SL
Circ Heart Fail: 16 Dec 2022:e009972; epub ahead of print | PMID: 36524472
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<div><h4>The Association of Protein Biomarkers With Incident Heart Failure With Preserved and Reduced Ejection Fraction.</h4><i>Takvorian KS, Wang D, Courchesne P, Vasan RS, ... Levy D, Ho JE</i><br /><b>Background</b><br />Heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) are distinct clinical entities, yet there is scant evidence for associations of proteomic signatures with future development of HFpEF versus HFrEF.<br /><b>Methods</b><br />We evaluated the association of 71 protein biomarkers with incident HFpEF versus HFrEF (left ventricular ejection fraction ≥ versus <50%) among Framingham Heart Study participants using multivariable Cox models.<br /><b>Results</b><br />Among 7038 participants (mean age 49 years; 54% women), 5 biomarkers were associated with increased risk of incident HFpEF (false discovery rate q<0.05): NT-proBNP (N-terminal pro-B-type natriuretic peptide; hazard ratio [HR]\' 2.13; 95% CI\' 1.52-2.99; <i>P</i><0.001), growth differentiation factor-15 (HR\' 1.67; 95% CI\' 1.32-2.12; <i>P</i><0.001), adrenomedullin (HR\' 1.58; 95% CI\' 1.23-2.04; <i>P</i><0.001), uncarboxylated matrix Gla protein (HR\' 1.55; 95% CI 1.23-1.95; <i>P</i><0.001), and C-reactive protein (HR\' 1.46; 95% CI\' 1.17-1.83; <i>P</i>=0.001). Fourteen biomarkers were associated with incident HFrEF (multivariable <i>P</i><0.001, q<0.05 for all). Of these, 3 biomarkers were associated with both HF subtypes (NT-proBNP, growth differentiation factor-15, and C-reactive protein). When compared directly, myeloperoxidase, resistin, and paraoxanase-1 were more strongly associated with HFrEF than HFpEF.<br /><b>Conclusions</b><br />We identified 5 protein biomarkers of new-onset HFpEF representing pathways of inflammation, cardiac stress, and vascular stiffness, which partly overlapped with HFrEF. We found 14 biomarkers associated with new-onset HFrEF, with some distinct associations including myeloperoxidase, resistin, and paraoxanase-1. Taken together, these findings provide insights into similarities and differences in the development of HF subtypes.<br /><b>Registration</b><br />URL: https://clinicaltrials.gov/ct2/show/NCT00005121; Unique identifier: NCT0005121.<br /><br /><br /><br /><small>Circ Heart Fail: 08 Dec 2022:e009446; epub ahead of print</small></div>
Takvorian KS, Wang D, Courchesne P, Vasan RS, ... Levy D, Ho JE
Circ Heart Fail: 08 Dec 2022:e009446; epub ahead of print | PMID: 36475777
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<div><h4>Assessing Heuristic Bias During Care for Patients Hospitalized for Heart Failure: Get With The Guidelines-Heart Failure.</h4><i>Selvaraj S, Greene SJ, Ayodele I, Alhanti B, ... Fonarow GC, Bhatt DL</i><br /><b>Background</b><br />Heuristic biases are increasingly recognized, and potentially modifiable, contributors to patient care and outcomes. Left digit bias is a cognitive bias where continuous variables are categorized by their left-most digit. The impact of this heuristic bias applied to patient age on quality of care in heart failure has not been explored.<br /><b>Methods</b><br />We examined participants admitted from 2005 to 2021 in the Get With The Guidelines-Heart Failure registry. To create 2 naturally randomized groups, isolating the effect of left digit bias, we dichotomized patients into those discharged within 60 days prior to their 80th birthday (N=4238) and those discharged within 60 days after their 80th birthday (N=4329). We performed multivariable logistic regression to assess the association between discharge date relative to 80th birthday and several in-hospital quality metrics and in-hospital outcomes. Among Medicare participants (N=2759), we performed adjusted Cox regression to analyze the relationship between discharge date and risk of 1-year mortality or readmission.<br /><b>Results</b><br />50.4% were female, 73% were non-Hispanic White, and 42.9% had an ejection fraction ≤40%. Discharge date relative to 80th birthday was not associated with numerous in-hospital quality metrics or in-hospital outcomes on unadjusted or adjusted logistic regression. Among Medicare beneficiaries, there was no association between discharge date and risk of mortality or readmission at 1-year postdischarge (hazard ratio, 1.03 [95% CI, 0.95-1.12]; <i>P</i>=0.52).<br /><b>Conclusions</b><br />In a large registry of patients hospitalized for heart failure, we did not detect a left digit bias\' with respect to age at discharge, which resulted in differential quality of care or outcomes.<br /><br /><br /><br /><small>Circ Heart Fail: 02 Dec 2022:e010069; epub ahead of print</small></div>
Selvaraj S, Greene SJ, Ayodele I, Alhanti B, ... Fonarow GC, Bhatt DL
Circ Heart Fail: 02 Dec 2022:e010069; epub ahead of print | PMID: 36458538
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<div><h4>Safety and Efficacy of Sacubitril/Valsartan in Patients With a Failing Systemic Right Ventricle: A Prospective Single-Center Study.</h4><i>Fusco F, Scognamiglio G, Merola A, Iannuzzi A, ... Grimaldi N, Sarubbi B</i><br /><b>Background</b><br />Sacubitril/valsartan was demonstrated to reduce hospitalization rate and mortality in patients with heart failure with reduced ejection fraction. Data on the effects of sacubitril/valsartan in patients with a systemic right ventricle are still lacking.<br /><b>Methods</b><br />Patients with transposition of the great arteries following Senning/Mustard procedure or congenitally corrected transposition of the great arteries with impaired systemic right ventricle systolic function were prospectively included. Primary end points included sacubitril/valsartan safety and efficacy. Primary efficacy end points were NT-proBNP (N-terminal pro-B-type natriuretic peptide) and systolic function improvement. Secondary end points included New York Heart Association class, 6-minute walking distance, and quality of life change.<br /><b>Results</b><br />Fifty patients (38±12 years, 60% male, 35% congenitally corrected transposition of the great arteries) were included and followed for 1 year. No major adverse events occurred. Two (4%) patients ceased treatment due to hypotension and 1 (2%) developed a nephrotic syndrome. The target dose was reached in 20 (42%) patients. NT-proBNP values decreased significantly immediately after treatment initiation, while returned to baseline at 1 year. Echocardiography showed progressive fractional area change increase (29.2±5.8 versus 34.9±5.1%; <i>P</i><0.001), and right ventricle global longitudinal strain (-13.9 [-15.1, -11.8] versus -15.3 [-17.2, -13.4]%; <i>P</i><0.001) and free-wall global longitudinal strain (-14.3 [-17.3, -12.3] versus -17.2 [-19.3, -15.8]%; <i>P</i><0.001) raise, whereas tricuspid regurgitation severity improved only in transposition of the great arteries patients (<i>P</i>=0.006). Moreover, 3-dimensional echocardiography demonstrated right ventricle volumes reduction (end-diastolic volume: 181±63 versus 156±50 mL; <i>P</i>=0.002; end-systolic volume: 117±48 versus 89±33 mL; <i>P</i><0.001), and significantly increased systemic right ventricle ejection fraction (35.6±8.1 versus 41.5±7.5%; <i>P</i><0.001). Clinical improvement was suggested by New York Heart Association class change (<i>P</i><0.001), increased 6-minute walking distance (425 [333, 480] versus 500 [443, 560] m; <i>P</i><0.001) as well as improved quality of life at 1-year follow-up. Beneficial effects were observed irrespective of the underlying anatomy and were more pronounced in those on target dose.<br /><b>Conclusions</b><br />Our data showed that sacubitril/valsartan is well tolerated and is associated with systemic right ventricle remodeling and improved systolic function as well as improved clinical status, supporting its use in this complex population.<br /><br /><br /><br /><small>Circ Heart Fail: 02 Dec 2022:e009848; epub ahead of print</small></div>
Fusco F, Scognamiglio G, Merola A, Iannuzzi A, ... Grimaldi N, Sarubbi B
Circ Heart Fail: 02 Dec 2022:e009848; epub ahead of print | PMID: 36458541
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<div><h4>Clinician and Algorithmic Application of the 2019 and 2022 Society of Cardiovascular Angiography and Intervention Shock Stages in the Critical Care Cardiology Trials Network Registry.</h4><i>Patel SM, Berg DD, Bohula EA, Baird-Zars VM, ... Morrow DA, CCCTN Investigators</i><br /><b>Background</b><br />Algorithmic application of the 2019 Society of Cardiovascular Angiography and Intervention (SCAI) shock stages effectively stratifies mortality risk for patients with cardiogenic shock. However, clinician assessment of SCAI staging may differ. Moreover, the implications of the 2022 SCAI criteria update remain incompletely defined.<br /><b>Methods</b><br />The Critical Care Cardiology Trials Network is a multicenter registry of cardiac intensive care units (CICUs). Between 2019 and 2021, participating centers (n=32) contributed at least a 2-month snapshot of consecutive medical CICU admissions. In-hospital mortality was assessed across 3 separate staging methods: clinician assessment, Critical Care Cardiology Trials Network algorithmic application of the 2019 SCAI criteria, and a revision of the Critical Care Cardiology Trials Network application using the 2022 SCAI criteria.<br /><b>Results</b><br />Of 9612 admissions, 1340 (13.9%) presented with cardiogenic shock with in-hospital mortality of 35.2%. Both clinician and algorithm-based staging using the 2019 SCAI criteria identified a stepwise gradient of mortality risk (stage C-E: 19.0% to 83.7% and 14.6% to 52.2%, respectively; <i>P</i><sub>trend</sub><0.001 for each). Clinician assignment of SCAI stages identified higher risk patients compared with algorithm-based assignment (stage D: 49.9% versus 29.3%; stage E: 83.7% versus 52.2%). Algorithmic application of the 2022 SCAI criteria, with incorporation of the vasoactive-inotropic score, more closely approximated clinician staging (mortality for stage C-E: 21.9% to 70.5%; <i>P</i><sub>trend</sub><0.001).<br /><b>Conclusions</b><br />Both clinician and algorithm-based application of the 2019 SCAI stages identify a stepwise gradient of mortality risk, although clinician-staging may better allocate higher risk patients into advanced SCAI stages. Updated algorithmic staging using the 2022 SCAI criteria and vasoactive-inotropic score further refines risk stratification.<br /><br /><br /><br /><small>Circ Heart Fail: 02 Dec 2022:e009714; epub ahead of print</small></div>
Patel SM, Berg DD, Bohula EA, Baird-Zars VM, ... Morrow DA, CCCTN Investigators
Circ Heart Fail: 02 Dec 2022:e009714; epub ahead of print | PMID: 36458542
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<div><h4>Multimarker Analysis of Serially Measured GDF-15, NT-proBNP, ST2, GAL-3, cTnI, Creatinine, and Prognosis in Acute Heart Failure.</h4><i>Gürgöze MT, van Vark LC, Baart SJ, Kardys I, ... Pinto YM, Boersma E</i><br /><b>Background</b><br />Studies on serially measured GDF-15 (growth differentiation factor 15) in acute heart failure (HF) are limited. Moreover, several pathophysiological pathways contribute to HF. Therefore, we aimed to explore the (additional) prognostic value of serially measured GDF-15 using a multi-marker approach to more accurately predict HF risk.<br /><b>Methods</b><br />TRIUMPH (Translational Initiative on Unique and Novel Strategies for Management of Patients With Heart Failure) is a prospective cohort of 496 patients with acute HF who were enrolled in 14 hospitals in the Netherlands between 2009 and 2014. Blood sampling was scheduled at 7 moments during 1-year follow-up. GDF-15, NT-proBNP (N-terminal pro-B-type natriuretic peptide), ST2 (suppression of tumorigenicity 2), galectin-3, troponin I, and creatinine were measured in a central laboratory. We associated repeated measurements of these biomarkers with the composite primary end point of all-cause mortality and HF rehospitalization, using multivariable joint modeling.<br /><b>Results</b><br />Median age was 74 years, and 37% were women. Median baseline GDF-15 was 4632 pg/mL. The primary end point was reached in 188 (40%) patients. The average estimated GDF-15 level increased weeks before the primary end point was reached. The hazard ratio per 1 SD difference in log-GDF-15 was 2.14 (95% CI, 1.78-2.57) unadjusted, 1.96 (1.49-2.53) after adjustment for clinical confounders and 1.44 (1.05-1.91) when jointly modeled with all biomarkers. The adjusted HRs for NT-proBNP were 2.38 (1.78-3.33) and 1.52 (1.15-2.08), respectively. The multimarker model combining GDF-15, NT-proBNP, and troponin I provided a favorable risk discrimination (area under the curve=0.785).<br /><b>Conclusions</b><br />Sequentially measured GDF-15 independently and dynamically predicts risk of adverse outcomes during 1-year follow-up after index admission for acute HF. NT-proBNP remains a robust predictor among potential candidates. Multiple biomarkers should be considered for stratification in clinical practice.<br /><b>Registration</b><br />URL: https://www.trialregister.nl/trial/1783; Unique Identifier: NTR1893. (The trial can be found temporarily at https://trialsearch.who.int/Trial2.aspx?TrialID=NTR1893.).<br /><br /><br /><br /><small>Circ Heart Fail: 21 Nov 2022:e009526; epub ahead of print</small></div>
Gürgöze MT, van Vark LC, Baart SJ, Kardys I, ... Pinto YM, Boersma E
Circ Heart Fail: 21 Nov 2022:e009526; epub ahead of print | PMID: 36408685
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<div><h4>Characteristics and Outcome of Patients With a History of Cancer Undergoing Durable Left Ventricular Assist Device Implantation.</h4><i>Tie H, Zhu J, Akin S, Allen LA, ... Caliskan K, Chen D</i><br /><b>Background</b><br />Patients with cancer (patients with a history of cancer) with advanced heart failure are increasing, but unlikely to be transplanted, and left ventricular assist device (LVAD) is an alternative strategy. This study investigates the characteristics and outcomes of patients with cancer undergoing durable LVAD.<br /><b>Methods</b><br />Adult patients with a history of cancer who received LVADs were identified from INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) registry: 2008 and 2017. Characteristics and outcomes between patients with cancer and those without cancer were compared, and subgroup analyses of cancer therapy-induced cardiomyopathy (CCM) and non-CCM were also conducted.<br /><b>Results</b><br />Overall, 1273 (6.5%) patients had a history of cancer, including 289 (22.7%) with CCM and 984 (77.3%) with non-CCM as the primary reason for heart failure. Patients with cancer had shorter median survival (3.72 versus 3.97 years, log-rank <i>P</i>=0.002), and multivariable Cox and competing risk regressions revealed that a history of cancer was associated with reduced survival (hazard ratio, 1.14 [95% CI, 1.04-1.26]; <i>P</i>=0.005; subdistribution hazard ratio, 1.24 [95% CI, 1.13-1.36]; <i>P<</i>0.001) and decreased incidence of heart transplantation. There was no significant difference in mortality between patients with CCM-induced heart failure and patients without cancer. Patients with cancer experienced an increased risk of bleeding, and age, INTERMACS profile, albumin, dialysis, and blood urea nitrogen were associated with mortality in these patients.<br /><b>Conclusions</b><br />A history of cancer is associated with mildly reduced survival, lower incidence of heart transplantation, and increased risk of bleeding after LVAD, whereas the survival in patients with cancer with CCM-induced heart failure is similar to those without cancer. LVAD implantation in patients with cancer is very well possible.<br /><br /><br /><br /><small>Circ Heart Fail: 14 Nov 2022:e009772; epub ahead of print</small></div>
Tie H, Zhu J, Akin S, Allen LA, ... Caliskan K, Chen D
Circ Heart Fail: 14 Nov 2022:e009772; epub ahead of print | PMID: 36373549
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<div><h4>Sodium Restriction in Patients With Heart Failure: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.</h4><i>Colin-Ramirez E, Sepehrvand N, Rathwell S, Ross H, ... McAlister FA, Ezekowitz JA</i><br /><b>Background</b><br />Sodium restriction is a nonpharmacologic treatment suggested by practice guidelines for the management of patients with heart failure (HF). In this study, we synthesized the data from randomized controlled trials (RCTs) evaluating the effects of sodium restriction on clinical outcomes in patients with HF.<br /><b>Methods</b><br />In this aggregate data meta-analysis, Cochrane Central, MEDLINE (Medical Literature Analysis and Retrieval System Online), Embase Ovid, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) Plus databases were searched up to April 2, 2022. RCTs were included if they investigated the effects of sodium/salt restriction as compared to no restriction on clinical outcomes in patients with HF. Outcomes of interest included mortality, hospitalization, change in New York Heart Association functional class, and quality of life (QoL).<br /><b>Results</b><br />Seventeen RCTs were identified (834 and 871 patients in intervention and control groups, respectively). Sodium restriction did not reduce the risk of all-cause death (odds ratio, 0.95 [95% CI, 0.58-1.58]), hospitalization (odds ratio, 0.84 [95% CI, 0.62-1.13]), or the composite of death/hospitalization (odds ratio, 0.88 [95% CI, 0.63-1.23]). The results were similar in different subgroups, except for the numerically lower risk of death with reduced sodium intake reported in RCTs with dietary sodium at the 2000 to 3000 mg/d range as opposed to <2000 mg/d (and in RCTs with versus without fluid restriction as a co-intervention). Among RCTs reporting New York Heart Association change, 2 RCTs (which accounted for two-thirds of the data) showed improvement in New York Heart Association class with sodium restriction. Substantial heterogeneity existed for QoL: 6 RCTs showed improvement of QoL and 4 RCTs showed no improvement of sodium restriction on QoL.<br /><b>Conclusions</b><br />In a meta-analysis of RCTs, sodium restriction was not associated with fewer deaths or hospitalizations in patients with HF. Dietary sodium restriction may be associated with improvements in symptoms and QoL.<br /><br /><br /><br /><small>Circ Heart Fail: 14 Nov 2022:e009879; epub ahead of print</small></div>
Colin-Ramirez E, Sepehrvand N, Rathwell S, Ross H, ... McAlister FA, Ezekowitz JA
Circ Heart Fail: 14 Nov 2022:e009879; epub ahead of print | PMID: 36373551
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<div><h4>Quality of Life Trajectory and Its Mediators in Older Patients With Acute Decompensated Heart Failure Receiving a Multi-Domain Rehabilitation Intervention: Results From the Rehabilitation Therapy in Older Acute Heart Failure Patients Trial.</h4><i>Whellan D, McCarey MM, Chen H, Nelson MB, ... Reeves G, Reed SD</i><br /><b>Background</b><br />As patients with heart failure experience worsening of their condition, including acute decompensated heart failure, quality of life deteriorates. However, the trajectory of quality of life changes and their determinants in the context of the Rehabilitation Therapy in Older Acute Heart Failure Patients trial physical rehabilitation intervention are unknown.<br /><b>Methods</b><br />Patients ≥60 years old admitted for acute decompensated heart failure (n=349) were randomized to either attention control or intervention. Quality of life outcomes (Kansas City Cardiomyopathy Questionnaire; 12-Item Short-Form Health Survey) were measured at baseline (inpatient), 1 month, and 3 months. Intervention effects were assessed using linear mixed effects regression, including covariates to model the main effects of the intervention and timing of outcome assessments. Mediation analysis determined if changes in Kansas City Cardiomyopathy Questionnaire were due to improvement in physical function (short physical performance battery, 6-minute walk distance).<br /><b>Results</b><br />Baseline Kansas City Cardiomyopathy Questionnaire summary score was similarly poor in the intervention and control arms (40.2±20.6 versus 41.5±20.6). Although the intervention experienced nominally greater Kansas City Cardiomyopathy Questionnaire improvement than control at 1 month (64.7±1.9 versus 61.1±1.9, <i>P</i>=0.13), the difference was not statistically significant until 3 months (67.7±1.9 versus 60.8±1.9, <i>P</i>=0.004). Twelve-Item Short-Form Health Survey Physical and Mental Composite Scores increased in both arms at 1 month and continued improvement only in the intervention. The 3-month improvement in short physical performance battery score explained 64.1% of the improvement in Kansas City Cardiomyopathy Questionnaire (<i>P</i><0.001).<br /><b>Conclusions</b><br />In older patients hospitalized for acute decompensated heart failure, quality of life improves in the first month after discharge. The quality of life benefit of a post-discharge physical rehabilitation intervention is detected early with large significant improvements at 3 months achieved primarily through improvement in short physical performance battery.<br /><b>Registration</b><br />URL: https://clinicaltrials.gov; Unique identifier: NCT02196038.<br /><br /><br /><br /><small>Circ Heart Fail: 08 Nov 2022:e009695; epub ahead of print</small></div>

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