Journal: Circ Heart Fail

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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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Abstract

Proposed Cardiac End Points for Clinical Trials in Immunoglobulin Light Chain Amyloidosis: Report From the Amyloidosis Forum Cardiac Working Group.

Maurer MS, Dunnmon P, Fontana M, Quarta CC, ... Lousada I, Merlini G
Immunoglobulin light chain amyloidosis is a rare, multisystemic, phenotypically heterogenous disease affecting cardiovascular, renal, neurological, and gastrointestinal systems to varying degrees. Its underlying cause is a plasma cell dyscrasia characterized by misfolding of monoclonal immunoglobulin light chains which leads to aggregation and deposition of insoluble amyloid fibrils in target organs. Prognosis is primarily dependent on extent of cardiac involvement and depth of hematologic response to treatment. To facilitate development of new therapies, a public-private partnership was formed between the nonprofit Amyloidosis Research Consortium and the US Food and Drug Administration Center for Drug Evaluation and Research. In 2020, the Amyloidosis Forum launched an initiative to identify novel/composite end points and analytic strategies to expedite clinical trials for development of new therapies for the primary hematologic disorder and organ system manifestations. Specialized working groups identified organ-specific end points; additional working groups reviewed health-related quality of life measures and statistical approaches to data analysis. Each working group comprised amyloidosis experts, patient representatives, statisticians, and representatives from the Food and Drug Administration, the UK Medicines and Healthcare Products Regulatory Agency, and pharmaceutical companies. This review summarizes the proceedings and recommendations of the Cardiac Working Group. Using a modified Delphi method, the group identified, reviewed, and prioritized cardiac end points relevant to immunoglobulin light chain amyloidosis in the context of an antiplasma cell therapy. Prioritized cardiovascular end points included overall survival, hospitalization, N-terminal pro-B-type natriuretic peptide level, 6-minute walk test, Kansas City Cardiac Questionnaire, and cardiac deterioration progression-free survival. These recommended components will be further explored through evaluation of clinical trial datasets and formal guidance from regulatory authorities.



Circ Heart Fail: 25 Mar 2022:CIRCHEARTFAILURE121009038; epub ahead of print
Maurer MS, Dunnmon P, Fontana M, Quarta CC, ... Lousada I, Merlini G
Circ Heart Fail: 25 Mar 2022:CIRCHEARTFAILURE121009038; epub ahead of print | PMID: 35331001
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Abstract

Development of Advanced Heart Failure: A Population-Based Study.

Subramaniam AV, Weston SA, Killian JM, Schulte PJ, ... Blecker SB, Dunlay SM
Background
Some patients with heart failure (HF) will go on to develop advanced HF, characterized by severe HF symptoms despite attempts to optimize medical therapy. The goals of this study were to examine the risk of developing advanced HF in patients with newly diagnosed HF, identify risk factors for developing advanced HF, and evaluate the impact of advanced HF on outcomes.
Methods
This was a population-based, retrospective cohort study of Olmsted County, Minnesota, residents with a new clinical diagnosis of HF between 2007 and 2017. Risk factors for the development of advanced HF (2018 European Society of Cardiology criteria) were examined using cause-specific Cox proportional hazard regression models. The associations of development of advanced HF with risks of hospitalization and mortality were examined using the Andersen-Gill and Cox models, respectively.
Results
There were 4597 residents with incident HF from 2007 to 2017. The cumulative incidence of advanced HF was 11.5% (95% CI, 10.5%-12.5%) at 6 years after incident HF diagnosis overall and was 14.4% (95% CI, 12.3%-16.9%), 11.4% (95% CI, 8.9%-14.6%), and 11.7% (95% CI, 10.3%-13.2%) in patients with incident HF with reduced, mildly reduced, and preserved ejection fraction, respectively. Key demographics, comorbidities, and echocardiographic characteristics were independently associated with the development of advanced HF. Development of advanced HF was associated with increased risks of all-cause hospitalization (adjusted hazard ratio, 3.0 [95% CI, 2.7-3.4]; P<0.001), HF hospitalization (hazard ratio, 10.2 [95% CI, 8.7-12.1]), all-cause mortality (hazard ratio, 5.0 [95% CI, 4.5-5.6]; P<0.001), and cardiovascular mortality (hazard ratio, 7.8 [95% CI, 6.7-9.1]).
Conclusions
In this population-based study, development of advanced HF was common and was associated with markedly increased morbidity and mortality.



Circ Heart Fail: 25 Mar 2022:CIRCHEARTFAILURE121009218; epub ahead of print
Subramaniam AV, Weston SA, Killian JM, Schulte PJ, ... Blecker SB, Dunlay SM
Circ Heart Fail: 25 Mar 2022:CIRCHEARTFAILURE121009218; epub ahead of print | PMID: 35332793
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Abstract

Combining Minimally Invasive Surgery With Ultra-Fast-Track Anesthesia in HeartMate 3 Patients: A Pilot Study.

Ahmad U, Khattab MA, Schaelte G, Goetzenich A, ... Schnoering H, Zayat R
Background
Minimally invasive surgery for left ventricular assist device implantation may have advantages over conventional sternotomy (CS). Additionally, ultra-fast-track anesthesia has been linked to better outcomes after cardiac surgery. This study summarizes our early experience of combining minimally invasive surgery with ultra-fast-track anesthesia (MIFTA) in patients receiving HeartMate 3 devices and compares the outcomes between MIFTA and CS.
Methods
From October 2015 to January 2019, 18 of 49 patients with Interagency Registry for Mechanically Assisted Circulatory Support profiles >1 underwent MIFTA for HeartMate 3 implantation. For bias reduction, propensity scores were calculated and used as a covariate in a regression model to analyze outcomes. Weighted parametric survival analysis was performed.
Results
In the MIFTA group, intensive care unit stays were shorter (mean difference, 8 days [95% CI, 4-13]; P<0.001), and the incidences of pneumonia and right heart failure were lower than those in the CS group (odds ratio, 1.36 [95% CI, 1.01-1.75]; P=0.016, respectively). At 6 and 12 hours postoperatively, MIFTA patients had a better hemodynamic performance with lower pulmonary wedge pressure (mean difference, 2.23 mm Hg [95% CI, 0.41-4.06]; P=0.028) and a higher right ventricular stroke work index (mean difference, -1.49 g·m/m2 per beat [95% CI, -2.95 to -0.02]; P=0.031). CS patients had a worse right heart failure-free survival rate (hazard ratio, 2.35 [95% CI, 0.96-5.72]; P<0.01).
Conclusions
Compared with CS, MIFTA is a beneficial approach for non-Interagency Registry for Mechanically Assisted Circulatory Support 1 HeartMate 3 patients with lower adverse event incidences, better hemodynamic performance, and preserved right heart function. Future large multicentric investigations are required to verify MIFTA\'s effects on outcomes.



Circ Heart Fail: 06 Mar 2022:CIRCHEARTFAILURE121008358; epub ahead of print
Ahmad U, Khattab MA, Schaelte G, Goetzenich A, ... Schnoering H, Zayat R
Circ Heart Fail: 06 Mar 2022:CIRCHEARTFAILURE121008358; epub ahead of print | PMID: 35249368
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Abstract

Validating an Idiopathic Dilated Cardiomyopathy Diagnosis Using Cardiovascular Magnetic Resonance: The Dilated Cardiomyopathy Precision Medicine Study.

Haas GJ, Zareba KM, Ni H, Bello-Pardo E, ... Hershberger RE, DCM Consortium Institutions and Personnel Participating in This Study
Background
Coronary angiography to identify coronary artery disease has been foundational to distinguish the cause of dilated cardiomyopathy (DCM), including the assignment of idiopathic or ischemic cardiomyopathy. Late gadolinium enhancement (LGE) with cardiovascular magnetic resonance (CMR) has emerged as an approach to identify myocardial scar and identify etiology.
Methods
The DCM Precision Medicine Study included patients with left ventricular dilation and dysfunction attributed to idiopathic DCM, after expert clinical review excluded ischemic or other cardiomyopathies. Ischemic cardiomyopathy was defined as coronary artery disease with >50% narrowing at angiography of ≥1 epicardial coronary artery. CMR was not required for study inclusion, but in a post hoc analysis of available CMR reports, patterns of LGE were classified as (1) no LGE, (2) ischemic-pattern LGE: subendocardial/transmural, (3) nonischemic LGE: midmyocardial/epicardial.
Results
Of 1204 idiopathic DCM patients evaluated, 396 (32.9%) had a prior CMR study; of these, 327 (82.6% of 396) had LGE imaging (mean age 46 years; 53.2% male; 55.4% White); 178 of the 327 (54.4%) exhibited LGE, and 156 of the 178 had LGE consistent with idiopathic DCM. The remaining 22 had transmural or subendocardial LGE. Of these 22, coronary angiography was normal (13), showed luminal irregularities (3), a distant thrombus (1), coronary artery disease with <50% coronary artery narrowing (1), or was not available (4).
Conclusions
Of 327 probands enrolled in the DCM Precision Medicine Study cohort who had LGE-CMR data available, an ischemic-pattern of LGE was identified in 22 (6.7%), all of whom had idiopathic DCM as adjudicated by expert clinical review.
Registration
URL: https://www.clinicaltrials.gov; Unique identifier: NCT03037632.



Circ Heart Fail: 03 Mar 2022:CIRCHEARTFAILURE121008877; epub ahead of print
Haas GJ, Zareba KM, Ni H, Bello-Pardo E, ... Hershberger RE, DCM Consortium Institutions and Personnel Participating in This Study
Circ Heart Fail: 03 Mar 2022:CIRCHEARTFAILURE121008877; epub ahead of print | PMID: 35240856
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Abstract

Management and Outcomes of Acute Myocardial Infarction-Cardiogenic Shock in Uninsured Compared With Privately Insured Individuals.

Vallabhajosyula S, Kumar V, Sundaragiri PR, Cheungpasitporn W, ... Bell MR, Barsness GW
Background
There are limited data on uninsured patients presenting with acute myocardial infarction-cardiogenic shock (AMI-CS). This study sought to compare the management and outcomes of AMI-CS between uninsured and privately insured individuals.
Methods
Using the National Inpatient Sample (2000-2016), a retrospective cohort of adult (≥18 years) uninsured admissions (primary payer-self-pay or no charge) were compared with privately insured individuals. Interhospital transfers were excluded. Outcomes of interest included in-hospital mortality, temporal trends in admissions, use of cardiac procedures, do-not-resuscitate status, palliative care referrals, and resource utilization.
Results
Of 402 182 AMI-CS admissions, 21 966 (5.4%) and 93 814 (23.3%) were uninsured and privately insured. Compared with private insured individuals, uninsured admissions were younger, male, from a lower socioeconomic status, had lower comorbidity, higher rates of acute organ failure, ST-segment elevation AMI-CS (77.3% versus 76.4%), and concomitant cardiac arrest (33.8% versus 31.9%; all P<0.001). Compared with 2000, in 2016, there were more uninsured (adjusted odds ratio, 1.15 [95% CI, 1.13-1.17]; P<0.001) and less privately insured admissions (adjusted odds ratio, 0.85 [95% CI, 0.83-0.87]; P<0.001). Uninsured individuals received less frequent coronary angiography (79.5% versus 81.0%), percutaneous coronary intervention (60.8% versus 62.2%), mechanical circulatory support (54% versus 55.5%), and had higher palliative care (3.8% versus 3.2%) and do-not-resuscitate status use (4.4% versus 3.2%; all P<0.001). Uninsured admissions had higher in-hospital mortality (adjusted odds ratio, 1.62 [95% CI, 1.55-1.68]; P<0.001) and resource utilization.
Conclusions
Uninsured individuals have higher in-hospital mortality and lower use of guideline-directed therapies in AMI-CS compared with privately insured individuals.



Circ Heart Fail: 03 Mar 2022:CIRCHEARTFAILURE121008991; epub ahead of print
Vallabhajosyula S, Kumar V, Sundaragiri PR, Cheungpasitporn W, ... Bell MR, Barsness GW
Circ Heart Fail: 03 Mar 2022:CIRCHEARTFAILURE121008991; epub ahead of print | PMID: 35240866
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Abstract

Developments in Exercise Capacity Assessment in Heart Failure Clinical Trials and the Rationale for the Design of METEORIC-HF.

Lewis GD, Docherty KF, Voors AA, Cohen-Solal A, ... Meng L, Felker GM
Heart failure with reduced ejection fraction (HFrEF) is a highly morbid condition for which exercise intolerance is a major manifestation. However, methods to assess exercise capacity in HFrEF vary widely in clinical practice and in trials. We describe advances in exercise capacity assessment in HFrEF and a comparative analysis of how various therapies available for HFrEF impact exercise capacity. Current guideline-directed medical therapy has indirect effects on cardiac performance with minimal impact on measured functional capacity. Omecamtiv mecarbil is a novel selective cardiac myosin activator that directly increases cardiac contractility and in a phase 3 cardiovascular outcomes study significantly reduced the primary composite end point of time to first heart failure event or cardiovascular death in patients with HFrEF. The objective of the METEORIC-HF trial (Multicenter Exercise Tolerance Evaluation of Omecamtiv Mecarbil Related to Increased Contractility in Heart Failure) is to assess the effect of omecamtiv mecarbil versus placebo on multiple components of functional capacity in HFrEF. The primary end point is to test the effect of omecamtiv mecarbil compared with placebo on peak oxygen uptake as measured by cardiopulmonary exercise testing after 20 weeks of treatment. METEORIC-HF will provide state-of-the-art assessment of functional capacity by measuring ventilatory efficiency, circulatory power, ventilatory anaerobic threshold, oxygen uptake recovery kinetics, daily activity, and quality-of-life assessment. Thus, the METEORIC-HF trial will evaluate the potential impact of increased myocardial contractility with omecamtiv mecarbil on multiple important measures of functional capacity in ambulatory patients with symptomatic HFrEF. Registration: URL: https://clinicaltrials.gov; Unique identifier: NCT03759392.



Circ Heart Fail: 02 Mar 2022:CIRCHEARTFAILURE121008970; epub ahead of print
Lewis GD, Docherty KF, Voors AA, Cohen-Solal A, ... Meng L, Felker GM
Circ Heart Fail: 02 Mar 2022:CIRCHEARTFAILURE121008970; epub ahead of print | PMID: 35236099
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Abstract

Targeting Preload in Heart Failure: Splanchnic Nerve Blockade and Beyond.

Fudim M, Khan MS, Paracha AA, Sunagawa K, Burkhoff D
Preload augmentation represents a critical mechanism for the cardiovascular system to increase effective circulating blood volume to increase cardiac filling pressures and, subsequently, for the heart to increase cardiac output. The splanchnic vascular compartment is the primary source of vascular capacity and thus the primary target for preload recruitment in humans. Under normal conditions, sympathetic stimulation of these primary venous vessels promotes the shift of blood from the splanchnic to the thoracic compartment and elevates preload and cardiac output. However, in heart failure, since filling pressures may be elevated at rest due to decreased venous capacitance, incremental recruitment of preload to enhance cardiac output may exacerbate congestion and limit exercise capacity. Accordingly, recent attention has focused on therapies designed to regulate splanchnic vascular redistribution to improve cardiac filling pressures and patient-centered outcomes such as quality of life and exercise capacity in patients with heart failure. In this review, we discuss the relevance of splanchnic circulation as a venous reservoir, the contribution of stressed blood volume to heart failure pathogenesis, and the implications for pharmacological therapeutic interventions to prevent heart failure decompensation. Further, we review emerging device-based approaches for cardiac preload reduction such as partial/complete occlusion of the superior vena cava or the inferior vena cava.



Circ Heart Fail: 27 Feb 2022; 15:e009340
Fudim M, Khan MS, Paracha AA, Sunagawa K, Burkhoff D
Circ Heart Fail: 27 Feb 2022; 15:e009340 | PMID: 35290092
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This program is still in alpha version.