Journal: Circ Heart Fail

Sorted by: date / impact
Abstract

The RAISE Trial: A Novel Device and First-in-Man Trial.

Sun W, Zou H, Yong Y, Liu B, ... Lotan C, Kong X
Background
Currently, standard medical therapies have limited effects on heart failure with preserved ejection fraction (HFpEF), which impacts on the life quality and survival of patients. This study aimed to evaluate the safety and efficacy of the percutaneous radiofrequency ablation-based interatrial shunting for HFpEF with a novel atrial septostomy device.
Methods
A preclinical study in 11 normal domestic pigs and the first-in-man study in 10 patients with HFpEF were performed. The major safety events and interatrial shunt performance were evaluated at baseline, 1 month, 3 months, and 6 months post-procedure in both animals and human patients. The clinical functional status was also assessed in the first-in-man study.
Results
Percutaneous radiofrequency ablation-based interatrial shunting therapy was performed successfully both in animals and patients. In the animal study, a left-to-right interatrial shunt was created with a mean defect size of 5.5±2.2 mm without procedure-related safety events. Seven pigs showed the continuous shunting with a mean defect size of 4.1±1.5 mm at 6 months. In the first-in-man study, a median interatrial defect diameter of 5.0 (4.0-6.0) mm was measured immediately. No major safety events including death and thromboembolism were observed. The continuous shunting with the defect size of 4.0 (3.0-4.0) mm could still be observed in 7 patients at 6 months. The clinical status was significantly improved with NT-proBNP (N-terminal pro-B-type natriuretic peptide) reduced by 2149 pg/mL ([95% CI, 204-3301] P=0.028), with 6-minute walk distance increased by 88 m ([95% CI, 50-249] P=0.008) and with New York Heart Association class improved in 8 patients at 6 months.
Conclusions
The present results showed that percutaneous radiofrequency ablation-based interatrial shunting was a safe and potentially effective therapy for HFpEF, providing a nonpharmacological and nonimplanted option for HFpEF management.
Registration
URL: https://www.chictr.org.cn; Unique identifier: ChiCTR1900027664.



Circ Heart Fail: 31 Mar 2022; 15:e008362
Sun W, Zou H, Yong Y, Liu B, ... Lotan C, Kong X
Circ Heart Fail: 31 Mar 2022; 15:e008362 | PMID: 35378984
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Testosterone, Hypogonadism, and Heart Failure.

Di Lodovico E, Facondo P, Delbarba A, Pezzaioli LC, ... Cappelli C, Ferlin A
Male hypogonadism is defined as low circulating testosterone level associated with signs and symptoms of testosterone deficiency. Although the bidirectional link between hypogonadism and cardiovascular disease has been clarified, the association between testosterone and chronic heart failure (HF) is more controversial. Herein, we critically review published studies relating to testosterone, hypogonadism, and HF and provide practical clinical information on proper diagnosis and treatment of male hypogonadism in patients with HF. In general, published studies are extremely heterogeneous, frequently have not adhered to hypogonadism guidelines, and suffer from many intrinsic methodological inaccuracies; therefore, data provide only low-quality evidence. Nevertheless, by selecting the few methodologically robust studies, we show the prevalence of testosterone deficiency (30%-50%) and symptomatic hypogonadism (15%) in men with HF is significant. Low testosterone correlates with HF severity, New York Heart Association class, exercise functional capacity, and a worse clinical prognosis and mortality. Interventional studies on testosterone treatment in men with HF are inconclusive but do suggest beneficial effects on exercise capacity, New York Heart Association class, metabolic health, and cardiac prognosis. We suggest that clinicians should measure testosterone levels in men with HF who have symptoms of a testosterone deficiency and conditions that predispose to hypogonadism, such as obesity and diabetes. These patients-if diagnosed as hypogonadal-may benefit from the short- and long-term effects of testosterone replacement therapy, which include improvements in both cardiac prognosis and systemic outcomes. Further collaborative studies involving both cardiologists and endocrinologists are warranted.



Circ Heart Fail: 08 Apr 2022:101161CIRCHEARTFAILURE121008755; epub ahead of print
Di Lodovico E, Facondo P, Delbarba A, Pezzaioli LC, ... Cappelli C, Ferlin A
Circ Heart Fail: 08 Apr 2022:101161CIRCHEARTFAILURE121008755; epub ahead of print | PMID: 35392658
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

The Value of Passive Leg Raise During Right Heart Catheterization in Diagnosing Heart Failure With Preserved Ejection Fraction.

van de Bovenkamp AA, Wijkstra N, Oosterveer FPT, Vonk Noordegraaf A, ... Borlaug BA, Handoko ML
Background
Because of limited accuracy of noninvasive tests, diastolic stress testing plays an important role in the diagnostic work-up of patients with heart failure with preserved ejection fraction (HFpEF). Exercise right heart catheterization is considered the gold standard and indicated when HFpEF is suspected but left ventricular filling pressures at rest are normal. However, performing exercise during right heart catheterization is not universally available. Here, we examined whether pulmonary capillary wedge pressure (PCWP) during a passive leg raise (PLR) could be used as simple and accurate method to diagnose or rule out occult-HFpEF.
Methods
In our tertiary center for pulmonary hypertension and HFpEF, all patients who received a diagnostic right heart catheterization with PCWP-measurements at rest, PLR, and exercise were evaluated (2014-2020). The diagnostic value of PCWPPLR was compared with the gold standard (PCWPEXERCISE). Cut-offs derived from our cohort were subsequently validated in an external cohort (N=74).
Results
Thirty-nine non-HFpEF, 33 occult-HFpEF, and 37 manifest-HFpEF patients were included (N=109). In patients with normal PCWPREST (<15 mmHg), PCWPPLR significantly improved diagnostic accuracy compared with PCWPREST (AUC=0.82 versus 0.69, P=0.03). PCWPPLR ≥19 mmHg (24% of cases) had a specificity of 100% for diagnosing occult-HFpEF, irrespective of diuretic use. PCWPPLR ≥11 mmHg had a 100% sensitivity and negative predictive value for diagnosing occult-HFpEF. Both cut-offs retained a 100% specificity and 100% sensitivity in the external cohort. Absolute change in PCWPPLR or V-wave derived parameters had no incremental value in diagnosing occult-HFpEF.
Conclusions
PCWPPLR is a simple and powerful tool that can help to diagnose or rule out occult-HFpEF.



Circ Heart Fail: 31 Mar 2022; 15:e008935
van de Bovenkamp AA, Wijkstra N, Oosterveer FPT, Vonk Noordegraaf A, ... Borlaug BA, Handoko ML
Circ Heart Fail: 31 Mar 2022; 15:e008935 | PMID: 35311526
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Outcomes With Phosphodiesterase-5 Inhibitor Use After Left Ventricular Assist Device: An STS-INTERMACS Analysis.

Grandin EW, Gulati G, Nunez JI, Kennedy K, ... Teuteberg J, Kiernan MS
Background
Elevated right ventricular afterload following continuous-flow left ventricular assist device (CF-LVAD) may contribute to late right heart failure (LRHF). PDE5i (phosphodiesterase-5 inhibitors) are used to treat pulmonary hypertension and right heart dysfunction after CF-LVAD, but their impact on outcomes is uncertain.
Methods
We queried Interagency Registry for Mechanically Assisted Circulatory Support from 2012 to 2017 for adults receiving a primary CF-LVAD and surviving ≥30 days from index discharge. Patients receiving early PDE5i (ePDE5i) at 1 month were propensity-matched 1:1 with controls. The primary outcome was the cumulative incidence of LRHF, defined using prevailing Interagency Registry for Mechanically Assisted Circulatory Support criteria; secondary outcomes included all-cause mortality and major bleeding.
Results
Among 9627 CF-LVAD recipients analyzed, 2463 (25.6%) received ePDE5i and 1600 were propensity-matched 1:1 with controls. Before implant, ePDE5i patients had more severe RV dysfunction (13.1% versus 9.6%) and higher pulmonary vascular resistance (2.8±2.7 versus 2.2±2.4 WU), both P<0.001, but clinical factors were well-balanced after propensity-matching. In the unmatched cohort, ePDE5i patients had a higher 3-year cumulative incidence of LRHF, mortality, and major bleeding, but these differences were attenuated in the propensity-matched cohort: LRHF 40.8% versus 35.7% (hazard ratio, 1.14 [95% CI, 0.99-1.32]; P=0.07); mortality 38.6% versus 35.8% (hazard ratio, 0.99 [95% CI, 0.86-1.15]; P=0.93); major bleeding 51.2% versus 46.0% (hazard ratio, 1.12 [95% CI, 0.99-1.27]; P=0.06).
Conclusions
Compared with propensity-matched controls, adult CF-LVAD patients receiving ePDE5i had similar rates of LRHF, mortality, and major bleeding. While intrinsic patient risk factors likely account for more adverse outcomes with ePDE5i in the unmatched cohort, there is no obvious benefit of ePDE5i in the LVAD population.



Circ Heart Fail: 31 Mar 2022; 15:e008613
Grandin EW, Gulati G, Nunez JI, Kennedy K, ... Teuteberg J, Kiernan MS
Circ Heart Fail: 31 Mar 2022; 15:e008613 | PMID: 35332780
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Skeletal Muscle Mass Recovery Early After Left Ventricular Assist Device Implantation in Patients With Advanced Systolic Heart Failure.

Vest AR, Wong WW, Chery J, Coston A, ... Kawabori M, Saltzman E
Background
Patients with advanced systolic heart failure are at risk of unintentional weight loss and muscle wasting. It has been observed that left ventricular assist device (LVAD) recipients gain weight after device implantation, although it is unknown whether this represents skeletal muscle mass gains. We aimed to determine whether skeletal muscle mass increases early during LVAD support.
Methods
We prospectively recruited 30 adults with systolic heart failure ±21 days from LVAD implantation. Participants underwent whole-body dual X-ray absorptiometry to measure fat free mass, appendicular lean mass (ALM, lean mass in the arms and legs) and fat mass. Dual X-ray absorptiometry imaging was repeated at 3 and 6 months after LVAD implantation, with participation ending after the 6-month visit or heart transplantation, whichever occurred first. Changes in body composition were evaluated using mixed effects linear regression models.
Results
The cohort was 87% male, with mean age 56±12 (SD) years, and mean body mass index 26.4±5.4 kg/m2. Per sarcopenia ALM criteria, 52% of participants had muscle wasting at baseline. At baseline, mean fat free mass and ALM were 56.4±11.7 and 21.0±5.3 kg, respectively. Both measures increased significantly (P<0.001) over 6 months of LVAD support: mean fat free mass change at 3 and 6 months: 2.3 kg (95% CI, 1.0-3.5) and 4.2 kg (95% CI, 2.2-6.1); mean ALM change at 3 and 6 months: 1.5 kg (95% CI, 0.7-2.3) and 2.3 kg (95% CI, 0.9-3.6).
Conclusions
Among LVAD recipients with advanced systolic heart failure and high baseline prevalence of muscle wasting, there were significant gains in skeletal muscle mass, as represented by dual X-ray absorptiometry fat free mass and ALM, over the first 6 months of LVAD support.



Circ Heart Fail: 05 Apr 2022:101161CIRCHEARTFAILURE121009012; epub ahead of print
Vest AR, Wong WW, Chery J, Coston A, ... Kawabori M, Saltzman E
Circ Heart Fail: 05 Apr 2022:101161CIRCHEARTFAILURE121009012; epub ahead of print | PMID: 35378982
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Mitochondrial Sirtuin-3 (SIRT3) Prevents Doxorubicin-Induced Dilated Cardiomyopathy by Modulating Protein Acetylation and Oxidative Stress.

Tomczyk MM, Cheung KG, Xiang B, Tamanna N, ... Tong Q, Dolinsky VW
Background
High doses of doxorubicin put cancer patients at risk for developing dilated cardiomyopathy. Previously, we showed that doxorubicin treatment decreases SIRT3 (sirtuin 3), the main mitochondrial deacetylase and increases protein acetylation in rat cardiomyocytes. Here, we hypothesize that SIRT3 expression can attenuate doxorubicin induced dilated cardiomyopathy in vivo by preventing the acetylation of mitochondrial proteins.
Methods
Nontransgenic, M3-SIRT3 (truncated SIRT3; short isoform), and M1-SIRT3 (full-length SIRT3; mitochondrial localized) transgenic mice were treated with doxorubicin for 4 weeks (8 mg/kg body weight per week). Echocardiography was performed to assess cardiac structure and function and validated by immunohistochemistry and immunofluorescence (n=4-10). Mass spectrometry was performed on cardiac mitochondrial peptides in saline (n=6) and doxorubicin (n=5) treated hearts. Validation was performed in doxorubicin treated primary rat and human induced stem cell derived cardiomyocytes transduced with adenoviruses for M3-SIRT3 and M1-SIRT3 and deacetylase deficient mutants (n=4-10).
Results
Echocardiography revealed that M3-SIRT3 transgenic mice were partially resistant to doxorubicin induced changes to cardiac structure and function whereas M1-SIRT3 expression prevented cardiac remodeling and dysfunction. In doxorubicin hearts, 37 unique acetylation sites on mitochondrial proteins were altered. Pathway analysis revealed these proteins are involved in energy production, fatty acid metabolism, and oxidative stress resistance. Increased M1-SIRT3 expression in primary rat and human cardiomyocytes attenuated doxorubicin-induced superoxide formation, whereas deacetylase deficient mutants were unable to prevent oxidative stress.
Conclusions
Doxorubicin reduced SIRT3 expression and markedly affected the cardiac mitochondrial acetylome. Increased M1-SIRT3 expression in vivo prevented doxorubicin-induced cardiac dysfunction, suggesting that SIRT3 could be a potential therapeutic target for mitigating doxorubicin-induced dilated cardiomyopathy.



Circ Heart Fail: 14 Apr 2022:101161CIRCHEARTFAILURE121008547; epub ahead of print
Tomczyk MM, Cheung KG, Xiang B, Tamanna N, ... Tong Q, Dolinsky VW
Circ Heart Fail: 14 Apr 2022:101161CIRCHEARTFAILURE121008547; epub ahead of print | PMID: 35418250
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Management of Hypertension in Patients With Ventricular Assist Devices: A Scientific Statement From the American Heart Association.

Eisen HJ, Flack JM, Atluri P, Bansal N, ... Rowe T, American Heart Association Heart Failure and Transplantation Committee of the Council on Clinical Cardiology; Council on Hypertension; and Council on Lifelong Congenital Heart Disease and Heart Health in the Young
Mechanical circulatory support with durable continuous-flow ventricular assist devices has become an important therapeutic management strategy for patients with advanced heart failure. As more patients have received these devices and the duration of support per patient has increased, the postimplantation complications have become more apparent, and the need for approaches to manage these complications has become more compelling. Continuous-flow ventricular assist devices, including axial-flow and centrifugal-flow pumps, are the most commonly used mechanical circulatory support devices. Continuous-flow ventricular assist devices and the native heart have a constant physiological interplay dependent on pump speed that affects pressure-flow relationships and patient hemodynamics. A major postimplantation complication is cerebrovascular vascular accidents. The causes of cerebrovascular vascular accidents in ventricular assist device recipients may be related to hypertension, thromboembolic events, bleeding from anticoagulation, or some combination of these. The most readily identifiable and preventable cause is hypertension. Hypertension management in these patients has been hampered by the fact that it is difficult to accurately measure blood pressure because these ventricular assist devices have continuous flow and are often not pulsatile. Mean arterial pressures have to be identified by Doppler or oscillometric cuff and treated. Although guidelines for hypertension management after ventricular assist device implantation are based largely on expert consensus and conventional wisdom, the mainstay of treatment for hypertension includes guideline-directed medical therapy for heart failure with reduced ejection fraction because this may reduce adverse effects associated with hypertension and increase the likelihood of favorable ventricular remodeling. The use of systemic anticoagulation in ventricular assist device recipients may at a given blood pressure increase the risk of stroke.



Circ Heart Fail: 18 Apr 2022:101161HHF0000000000000074; epub ahead of print
Eisen HJ, Flack JM, Atluri P, Bansal N, ... Rowe T, American Heart Association Heart Failure and Transplantation Committee of the Council on Clinical Cardiology; Council on Hypertension; and Council on Lifelong Congenital Heart Disease and Heart Health in the Young
Circ Heart Fail: 18 Apr 2022:101161HHF0000000000000074; epub ahead of print | PMID: 35430896
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Blood Pressure and Glycemic Control Among Ambulatory US Adults With Heart Failure: National Health and Nutrition Examination Survey 2001 to 2018.

Rethy L, Vu TT, Shah NS, Carnethon MR, ... Lloyd-Jones DM, Khan SS
Background
Multisociety guidelines recommend a goal systolic blood pressure (BP) <130 mm Hg and a hemoglobin A1c (HbA1c) <8% in patients with heart failure (HF), regardless of ejection fraction. Few studies have described BP and glycemic control in ambulatory patients with HF and racial and ethnic disparities in this subset of the population.
Methods
We evaluated prevalence of uncontrolled BP and HbA1c in non-Hispanic Black, non-Hispanic White, and Mexican American adults aged ≥20 years with self-reported HF (National Health and Nutrition Examination Surveys: 2001-2018). Prevalence ratios (95% CI) for uncontrolled BP and HbA1c were calculated by race and ethnicity and adjusted for sex, age, treatment, and socioeconomic status. In secondary analyses, we examined trends in the prevalence of uncontrolled BP and HbA1c.
Results
Uncontrolled BP was present in 48% (95% CI, 49%-56%) of adults with HF (representing 2.3 million people). Non-Hispanic Black participants had a higher prevalence of uncontrolled BP compared with non-Hispanic White participants (53% [48%-58%] compared with 47% [43%-51%], P<0.05). In adjusted models, non-Hispanic Black participants were 1.19 (1.02-1.39) times more likely to have uncontrolled BP than non-Hispanic White participants. Overall, uncontrolled HbA1c was found in 8% (6%, 10%) with no differences by race and ethnicity. Prevalence of uncontrolled BP improved over time but uncontrolled risk factors remained high-2017 to 2018: 41% (36%, 47%) and 7% (5%, 12%) had uncontrolled BP and HbA1c, respectively.
Conclusions
We document an unacceptably high prevalence of uncontrolled BP and HbA1c in a nationally representative, ambulatory HF sample with significant differences in BP control by race and ethnicity.



Circ Heart Fail: 28 Apr 2022:101161CIRCHEARTFAILURE121009229; epub ahead of print
Rethy L, Vu TT, Shah NS, Carnethon MR, ... Lloyd-Jones DM, Khan SS
Circ Heart Fail: 28 Apr 2022:101161CIRCHEARTFAILURE121009229; epub ahead of print | PMID: 35477292
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Cardiogenic Shock From Heart Failure Versus Acute Myocardial Infarction: Clinical Characteristics, Hospital Course, and 1-Year Outcomes.

Sinha SS, Rosner CM, Tehrani BN, Maini A, ... O\'Connor CM, Batchelor WB
Background
Little is known about clinical characteristics, hospital course, and longitudinal outcomes of patients with cardiogenic shock (CS) related to heart failure (HF-CS) compared to acute myocardial infarction (AMI; CS related to AMI [AMI-CS]).
Methods
We examined in-hospital and 1-year outcomes of 520 (219 AMI-CS, 301 HF-CS) consecutive patients with CS (January 3, 2017-December 31, 2019) in a single-center registry.
Results
Mean age was 61.5±13.5 years, 71% were male, 22% were Black patients, and 63% had chronic kidney disease. The HF-CS cohort was younger (58.5 versus 65.6 years, P<0.001), had fewer cardiac arrests (15.9% versus 35.2%, P<0.001), less vasopressor utilization (61.8% versus 82.2%, P<0.001), higher pulmonary artery pulsatility index (2.14 versus 1.51, P<0.01), lower cardiac power output (0.64 versus 0.77 W, P<0.01) and higher pulmonary capillary wedge pressure (25.4 versus 22.2 mm Hg, P<0.001) than patients with AMI-CS. Patients with HF-CS received less temporary mechanical circulatory support (34.9% versus 76.3% P<0.001) and experienced lower rates of major bleeding (17.3% versus 26.0%, P=0.02) and in-hospital mortality (23.9% versus 39.3%, P<0.001). Postdischarge, 133 AMI-CS and 229 patients with HF-CS experienced similar rates of 30-day readmission (19.5% versus 24.5%, P=0.30) and major adverse cardiac and cerebrovascular events (23.3% versus 28.8%, P=0.45). Patients with HF-CS had lower 1-year mortality (n=123, 42.6%) compared to the patients with AMI-CS (n=110, 52.9%, P=0.03). Cumulative 1-year mortality was also lower in patients with HF-CS (log-rank test, P=0.04).
Conclusions
Patients with HF-CS were younger, and despite lower cardiac power output and higher pulmonary capillary wedge pressure, less likely to receive vasopressors or temporary mechanical circulatory support. Although patients with HF-CS had lower in-hospital and 1-year mortality, both cohorts experienced similarly high rates of postdischarge major adverse cardiovascular and cerebrovascular events and 30-day readmission, highlighting that both cohorts warrant careful long-term follow-up.
Registration
URL: https://www.
Clinicaltrials
gov; Unique identifier: NCT03378739.



Circ Heart Fail: 05 May 2022:101161CIRCHEARTFAILURE121009279; epub ahead of print
Sinha SS, Rosner CM, Tehrani BN, Maini A, ... O'Connor CM, Batchelor WB
Circ Heart Fail: 05 May 2022:101161CIRCHEARTFAILURE121009279; epub ahead of print | PMID: 35510546
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Defects in the Proteome and Metabolome in Human Hypertrophic Cardiomyopathy.

Previs MJ, O\'Leary TS, Morley MP, Palmer BM, ... Kelly DP, Day SM
Background
Defects in energetics are thought to be central to the pathophysiology of hypertrophic cardiomyopathy (HCM); yet, the determinants of ATP availability are not known. The purpose of this study is to ascertain the nature and extent of metabolic reprogramming in human HCM, and its potential impact on contractile function.
Methods
We conducted proteomic and targeted, quantitative metabolomic analyses on heart tissue from patients with HCM and from nonfailing control human hearts.
Results
In the proteomic analysis, the greatest differences observed in HCM samples compared with controls were increased abundances of extracellular matrix and intermediate filament proteins and decreased abundances of muscle creatine kinase and mitochondrial proteins involved in fatty acid oxidation. These differences in protein abundance were coupled with marked reductions in acyl carnitines, byproducts of fatty acid oxidation, in HCM samples. Conversely, the ketone body 3-hydroxybutyrate, branched chain amino acids, and their breakdown products, were all significantly increased in HCM hearts. ATP content, phosphocreatine, nicotinamide adenine dinucleotide and its phosphate derivatives, NADP and NADPH, and acetyl CoA were also severely reduced in HCM compared with control hearts. Functional assays performed on human skinned myocardial fibers demonstrated that the magnitude of observed reduction in ATP content in the HCM samples would be expected to decrease the rate of cross-bridge detachment. Moreover, left atrial size, an indicator of diastolic compliance, was inversely correlated with ATP content in hearts from patients with HCM.
Conclusions
HCM hearts display profound deficits in nucleotide availability with markedly reduced capacity for fatty acid oxidation and increases in ketone bodies and branched chain amino acids. These results have important therapeutic implications for the future design of metabolic modulators to treat HCM.



Circ Heart Fail: 11 May 2022:CIRCHEARTFAILURE121009521; epub ahead of print
Previs MJ, O'Leary TS, Morley MP, Palmer BM, ... Kelly DP, Day SM
Circ Heart Fail: 11 May 2022:CIRCHEARTFAILURE121009521; epub ahead of print | PMID: 35543134
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Estrogen Protects Cardiac Function and Energy Metabolism in Dilated Cardiomyopathy Induced by Loss of Cardiac IRS1 and IRS2.

Yan H, Yang W, Zhou F, Pan Q, ... Tong C, Guo S
Background
Type 2 diabetes (T2D) is a high-risk factor for incident of cardiovascular diseases. Women at young ages show a reduced incidence of both T2D and cardiovascular diseases compared with men, but these disparities disappear in postmenopausal women versus age-matched men. Thus, ovaries and ovarian hormones, such as estrogen, are expected to protect from T2D and cardiovascular diseases. In this study, we aimed to investigate the role of ovaries and ovarian hormone estrogen in cardiac function and energy metabolism using the cardiac IRS (insulin receptor substrate) 1 and IRS2 double genes knockout mice that mimic cardiac insulin resistance.
Methods
Control and heart-specific IRS1/2 double genes knockout mice were treated with placebo or 17β-estradiol (E2) pellets, respectively, through subcutaneous implantation. Female mice were subjected to a bilateral ovariectomy surgery to remove endogenous E2. The cardiac function and energy metabolism were determined using echocardiography and indirect calorimeter, respectively.
Results
All male heart-specific IRS1/2 double genes knockout mice died of heart failure at 6 to 8 weeks as we previously described (Qi et al), but all female heart-specific IRS1/2 double genes knockout mice survived >1 year. Removal of ovaries in heart-specific IRS1/2 double genes knockout female mice resulted in cardiac dysfunction, and ultimately animal death. However, E2 supplementation prevented the dilated cardiomyopathy, improved cardiac function and energy metabolism, and enhanced lifespan in both male and ovariectomy female mice deficient for cardiac IRS1 and IRS2 genes, largely owing to the activation of Akt (protein kinase B)-Foxo1 (O1 class of forkhead/winged helix transcription factor) signaling cascades.
Conclusions
These results show that estrogen protects mice from cardiac insulin resistance-induced diabetic cardiomyopathy. This may provide a fundamental mechanism for the gender difference for the incidence of both T2D and cardiovascular diseases. This study highlights that estrogen signaling could be a potential target for improving cardiac function and energy metabolism in humans with T2D.



Circ Heart Fail: 17 May 2022:101161CIRCHEARTFAILURE121008758; epub ahead of print
Yan H, Yang W, Zhou F, Pan Q, ... Tong C, Guo S
Circ Heart Fail: 17 May 2022:101161CIRCHEARTFAILURE121008758; epub ahead of print | PMID: 35579013
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Alcohol Intake in Patients With Cardiomyopathy and Heart Failure: Consensus and Controversy.

Andersson C, Schou M, Gustafsson F, Torp-Pedersen C
Alcohol is often cited to be a common cause of cardiomyopathy and heart failure. However, in most available population-based studies, a modest-to-moderate alcohol consumption has been associated with favorable effects on the cardiovascular system, including a lowered risk of heart failure, compared with no alcohol consumption. Available genetic epidemiological data have not supported a causal association between alcohol consumption and heart failure risk, suggesting that alcohol may not be a common cause of heart failure in the community. Data linking alcohol intake with cardiomyopathy risk are sparse, and the concept of alcoholic cardiomyopathy stems mainly from case series of selected patients with dilated cardiomyopathy, where a large proportion reported a history of excessive alcohol intake. This state-of-the-art paper addresses the current knowledge of the epidemiology of alcoholic cardiomyopathy and the role of alcohol intake in patients with non-alcohol-related heart failure. It also offers directions to future research in the area. The review questions the validity of current clinical teaching in the area. It is not well known how much alcohol is needed to cause disease, and the epidemiological pathways linking alcohol consumption to cardiomyopathy and heart failure are not well understood. Until more evidence becomes available, caution is warranted before labeling patients as having alcoholic cardiomyopathy due to a risk of neglecting other contributors, such as genetic causes of cardiomyopathy. In non-alcohol-related heart failure, it is unknown whether total abstinence is improving outcomes (compared with moderate drinking). Ideally, randomized clinical trials are needed to answer this question.



Circ Heart Fail: 20 May 2022:101161CIRCHEARTFAILURE121009459; epub ahead of print
Andersson C, Schou M, Gustafsson F, Torp-Pedersen C
Circ Heart Fail: 20 May 2022:101161CIRCHEARTFAILURE121009459; epub ahead of print | PMID: 35593142
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Right Heart Failure Following Left Ventricular Device Implantation: Natural History, Risk Factors, and Outcomes: An Analysis of the STS INTERMACS Database.

Kapelios CJ, Lund LH, Wever-Pinzon O, Selzman CH, ... Kirklin JK, Drakos SG
Background
Our current understanding of right heart failure (RHF) post-left ventricular assist device (LVAD) is lacking. Recently, a new Interagency Registry for Mechanically Assisted Circulatory Support definition of RHF was introduced. Based on this definition, we investigated natural history, risk factors, and outcomes of post-LVAD RHF.
Methods
Patients implanted with continuous flow LVAD between June 2, 2014, and June 30, 2016 and registered in the Interagency Registry for Mechanically Assisted Circulatory Support/Society of Thoracic Surgeons Database were included. RHF incidence and predictors, and survival after RHF were assessed. The manifestations of RHF which were separately analyzed were elevated central venous pressure, peripheral edema, ascites, and use of inotropes.
Results
Among 5537 LVAD recipients (mean 57±13 years, 49% destination therapy, support 18.9 months) prevalence of 1-month RHF was 24%. Of these, RHF persisted at 12 months in 5.3%. In contrast, de novo RHF, first identified at 3 months, occurred in 5.1% and persisted at 12 months in 17% of these, and at 6 months occurred in 4.8% and persisted at 12 months in 25%. Higher preimplant blood urea nitrogen (ORs,1.03-1.09 per 5 mg/dL increase; P<0.0001), previous tricuspid valve repair/replacement (ORs, 2.01-10.09; P<0.001), severely depressed right ventricular systolic function (ORs,1.17-2.20; P=0.004); and centrifugal versus axial LVAD (ORs,1.15-1.78; P=0.001) represented risk factors for RHC incidence at 3 months. Patients with persistent RHF at 3 months had the lowest 2-year survival (57%) while patients with de novo RHF or RHF which resolved by 3 months had more favorable survival outcomes (75% and 78% at 2 years, respectively; P<0.001).
Conclusions
RHF at 1 or 3 months post-LVAD was a common and frequently transient condition, which, if resolved, was associated with relatively favorable prognosis. Conversely, de novo, late RHF post-LVAD (>6 months) was more frequently a persistent disorder and associated with increased mortality. The 1-, 3-, and 6-month time points may be used for RHF assessment and risk stratification in LVAD recipients.



Circ Heart Fail: 06 Jun 2022:101161CIRCHEARTFAILURE121008706; epub ahead of print
Kapelios CJ, Lund LH, Wever-Pinzon O, Selzman CH, ... Kirklin JK, Drakos SG
Circ Heart Fail: 06 Jun 2022:101161CIRCHEARTFAILURE121008706; epub ahead of print | PMID: 35658464
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Vericiguat and Health-Related Quality of Life in Patients With Heart Failure With Reduced Ejection Fraction: Insights From the VICTORIA Trial.

Butler J, Stebbins A, Melenovský V, Sweitzer NK, ... Armstrong PW, VICTORIA Study Group
Background
We examined the effects of vericiguat compared with placebo in patients with heart failure with reduced ejection fraction enrolled in VICTORIA (Vericiguat Global Study in Patients With Heart Failure With Reduced Ejection Fraction) on health status outcomes measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) and evaluated whether clinical outcomes varied by baseline KCCQ score.
Methods
KCCQ was completed at baseline and 4, 16, and 32 weeks. We assessed treatment effect on KCCQ using a mixed-effects model adjusting for baseline KCCQ and stratification variables. Cox proportional-hazards modeling was performed to evaluate the effect of vericiguat on clinical outcomes by tertiles of baseline KCCQ clinical summary score (CSS), total symptom score (TSS), and overall summary score (OSS).
Results
Of 5050 patients, 4664, 4741, and 4470 had KCCQ CSS (median [25th to 75th], 65.6 [45.8-81.8]), TSS (68.8 [47.9-85.4]), and OSS (59.9 [42.0-77.1]) at baseline; 94%, 88%, and 82% had data at 4, 16, and 32 weeks. At 16 weeks, CSS improved by a median of 6.3 in both arms; no significant differences in improvement were seen for TSS and OSS between the 2 groups (P=0.69, 0.97, and 0.13 for CSS, TSS, and OSS). Trends were similar at 4 and 32 weeks. Vericiguat versus placebo reduced cardiovascular death or heart failure hospitalization risk similarly across tertiles of baseline KCCQ CSS, TSS, and OSS (interaction P=0.13, 0.21, and 0.65).
Conclusions
Vericiguat did not significantly improve KCCQ scores compared with placebo. Vericiguat reduced the risk of cardiovascular death or heart failure hospitalization across the range of baseline health status.
Registration
URL: https://www.
Clinicaltrials
gov; Unique identifier: NCT02861534.



Circ Heart Fail: 03 Jun 2022:101161CIRCHEARTFAILURE121009337; epub ahead of print
Butler J, Stebbins A, Melenovský V, Sweitzer NK, ... Armstrong PW, VICTORIA Study Group
Circ Heart Fail: 03 Jun 2022:101161CIRCHEARTFAILURE121009337; epub ahead of print | PMID: 35656822
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Diurnal Variations in Natriuretic Peptide Levels: Clinical Implications for the Diagnosis of Acute Heart Failure.

Breidthardt T, van Doorn WPTM, van der Linden N, Diebold M, ... Meex SJR, Mueller C
Background
Current guidelines recommend interpreting concentrations of NPs (natriuretic peptides) irrespective of the time of presentation to the emergency department. We hypothesized that diurnal variations in NP concentration may affect their diagnostic accuracy for acute heart failure.
Methods
In a secondary analysis of a multicenter diagnostic study enrolling patients presenting with acute dyspnea to the emergency department and using central adjudication of the final diagnosis by 2 independent cardiologists, the diagnostic accuracy for acute heart failure of BNP (B-type NP), NT-proBNP (N-terminal pro-B-type NP), and MR-proANP (midregional pro-atrial NP) was compared among 1577 daytime presenters versus 908 evening/nighttime presenters. In a validation study, the presence of a diurnal rhythm in BNP and NT-proBNP concentrations was examined by hourly measurements in 44 stable individuals.
Results
Among patients adjudicated to have acute heart failure, BNP, NT-proBNP, and MR-proANP concentrations were comparable among daytime versus evening/nighttime presenters (all P=nonsignificant). Contrastingly, among patients adjudicated to have other causes of dyspnea, evening/nighttime presenters had lower BNP (median, 44 [18-110] versus 74 [27-168] ng/L; P<0.01) and NT-proBNP (median, 212 [72-581] versus 297 [102-902] ng/L; P<0.01) concentrations versus daytime presenters. This resulted in higher diagnostic accuracy as quantified by the area under the curve of BNP and NT-proBNP among evening/nighttime presenters (0.97 [95% CI, 0.95-0.98] and 0.95 [95% CI, 0.93-0.96] versus 0.94 [95% CI, 0.92-0.95] and 0.91 [95% CI, 0.90-0.93]) among daytime presenters (both P<0.01). These differences were not observed for MR-proANP. Diurnal variation of BNP and NT-proBNP with lower evening/nighttime concentration was confirmed in 44 stable individuals (P<0.01).
Conclusions
BNP and NT-proBNP, but not MR-proANP, exhibit a diurnal rhythm that results in even higher diagnostic accuracy among evening/nighttime presenters versus daytime presenters.
Registration
URL: https://www.
Clinicaltrials
gov; Unique identifiers: NCT01831115, NCT02091427, and NCT02210897.



Circ Heart Fail: 07 Jun 2022:101161CIRCHEARTFAILURE121009165; epub ahead of print
Breidthardt T, van Doorn WPTM, van der Linden N, Diebold M, ... Meex SJR, Mueller C
Circ Heart Fail: 07 Jun 2022:101161CIRCHEARTFAILURE121009165; epub ahead of print | PMID: 35670217
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Role of Implantable Cardioverter Defibrillator in Heart Failure With Contemporary Medical Therapy.

Butler J, Talha KM, Aktas MK, Zareba W, Goldenberg I
Implantable cardioverter defibrillator therapy is indicated in a subset of patients with heart failure with reduced ejection as primary prevention for sudden cardiac death. The advent of novel medical therapies including mineralocorticoid receptor antagonists, angiotensin receptor blocker/neprilysin inhibitors, and sodium-glucose transporter 2 inhibitor in the past 2 decades has revolutionized heart failure with reduced ejection management. Current guideline-directed medical therapy has reduced all-cause mortality and sudden cardiac death and confers a considerable improvement in left ventricular ejection fraction over a short period of time. However, there is limited evidence at present to suggest whether implantable cardioverter defibrillator therapy continues to have the same benefit in sudden cardiac death prevention at current left ventricular ejection fraction cutoff indications for patients on contemporary guideline-directed medical therapy for heart failure with reduced ejection. In this review, the authors propose in lieu of current evidence that it is reasonable to reevaluate indications for implantable cardioverter defibrillator therapy in patients on contemporary guideline-directed medical therapy for heart failure with reduced ejection.



Circ Heart Fail: 21 Jun 2022:CIRCHEARTFAILURE122009634; epub ahead of print
Butler J, Talha KM, Aktas MK, Zareba W, Goldenberg I
Circ Heart Fail: 21 Jun 2022:CIRCHEARTFAILURE122009634; epub ahead of print | PMID: 35726617
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Donor Utilization in the Recent Era: Effect of Sex, Drugs, and Increased Risk.

Baran DA, Long A, Lansinger J, Copeland JG, Copeland H
Background
Heart transplantation volumes have increased in recent years, yet less than a third of donors are typically accepted for transplantation. Whether donor sex, donor drug use, or perception of increased risk affects utilization for transplantation is unclear.
Methods
The United Network for Organ Sharing database was queried for donors from January 1, 2007, to December 31, 2017. Donor toxicology was collected when available. Multivariate analysis was conducted to examine correlations with donor utilization.
Results
Between January 1, 2007, and December 31, 2017, there were 87 816 heart donors aged ≥15 years. The mean age was 42.7±15.8 years, and 24 831 donors (28.3%) were utilized for heart transplantation. Subsequent analyses focused on donors between 15 and 39 years old. The strongest associations with donor acceptance were for male donor sex, blood type, hepatitis C antibody, donor age, left ventricular hypertrophy, and history of donor drug use. After removing hepatitis C, Public Health Service Increased Risk was identified as a strong negative predictor. Most positive drug toxicology results were associated with donor nonuse except for donors between 15 and 19 years of age. Exceptions included alcohol, marijuana, and cocaine. Opiates were associated with less utilization at all donor ages. The Public Health Service Increased Risk status was associated with significantly less utilization in all age groups except 15- to 19-year-old donors.
Conclusions
While male donors were preferentially utilized, donors with drug use or those deemed Public Health Service Increased Risk were significantly less utilized for heart transplantation. Further consideration of such donors would be appropriate particularly as the demand for transplantation continues to increase.



Circ Heart Fail: 21 Jun 2022:101161CIRCHEARTFAILURE122009547; epub ahead of print
Baran DA, Long A, Lansinger J, Copeland JG, Copeland H
Circ Heart Fail: 21 Jun 2022:101161CIRCHEARTFAILURE122009547; epub ahead of print | PMID: 35726629
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Estrogen Receptor-β Agonists Modulate T-Lymphocyte Activation and Ameliorate Left Ventricular Remodeling During Chronic Heart Failure.

Rosenzweig R, Kumar V, Gupta S, Bermeo-Blanco O, ... Gumina RJ, Bansal SS
Background
CD4+ T cells temporally transition from protective to pathological during ischemic heart failure (HF; 8 weeks postmyocardial infarction). Cellular mechanisms mediating this shift are unknown.
Methods
RNA-sequencing of cardiac CD4+ T cells and flow cytometric analysis of immune cells was conducted.
Results
RNA-sequencing of CD4+ T cells from the failing hearts of male mice indicated activation of ER (estrogen receptor)-α signaling. Flow cytometric analysis showed that ERα in CD4+ T cells decreases significantly at 3-day postmyocardial infarction but increases during HF. To antagonize ERα, we tested a novel ERβ agonist (OSU-ERb-012) to inhibit T cells and blunt left ventricular remodeling. Proliferation assays showed that OSU-ERb-012 dose-dependently inhibited proliferation and proinflammatory cytokine expression in anti-CD3/CD28 stimulated splenic T cells isolated from both the sexes. For in vivo efficacy, 10- to 12-week-old male and ovariectomized female mice were randomized at 4 weeks postmyocardial infarction and treated with either vehicle or drug (60 mg/kg per day; oral). While vehicle-treated HF mice displayed progressive left ventricular dilatation with significantly increased end-systolic and end-diastolic volumes from 4 to 8 weeks postmyocardial infarction, treatment with OSU-ERb-012 significantly blunted these changes and stopped left ventricular remodeling in both the sexes. Reduction in tibia-normalized heart and left ventricular weights, cardiomyocyte hypertrophy and interstitial fibrosis further supported these results. Additionally, OSU-ERb-012 treatment selectively inhibited cardiac, splenic, and circulating CD4+ T cells without affecting other myeloid and lymphoid cells in the HF mice.
Conclusions
Our studies indicate that ERβ agonists and OSU-ERb-012, in particular, could be used as selective immunomodulatory drugs to inhibit CD4+ T cells during chronic HF.



Circ Heart Fail: 22 Jun 2022:CIRCHEARTFAILURE121008997; epub ahead of print
Rosenzweig R, Kumar V, Gupta S, Bermeo-Blanco O, ... Gumina RJ, Bansal SS
Circ Heart Fail: 22 Jun 2022:CIRCHEARTFAILURE121008997; epub ahead of print | PMID: 35730443
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:

This program is still in alpha version.