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1.
Rev. urug. cardiol ; 37(1): e408, jun. 2022. ilus, graf
Article in Spanish | UY-BNMED, LILACS, BNUY | ID: biblio-1415379

ABSTRACT

La insuficiencia cardíaca con fracción de eyección preservada (ICFEp) y reducida presentan marcadas diferencias. Mientras que la última tiene un algoritmo diagnóstico y terapéutico desde hace años, con guías y fármacos que mejoran su pronóstico, la ICFEp no solo presenta dificultades para llegar al diagnóstico, sino que tampoco hay fármacos que hayan demostrado disminuir la mortalidad. En esta revisión se hace un abordaje amplio de la ICFEp, comenzando por definirla y distinguirla de la disfunción diastólica. Se describe el gold standard para su diagnóstico invasivo y se analizan los scores no invasivos recientemente desarrollados que estiman la probabilidad de tener la enfermedad. A través del análisis de las comorbilidades frecuentemente asociadas, se describen los mecanismos fisiopatológicos implicados. Asimismo, se detallan los fenotipos propuestos para agrupar pacientes y diseñar ensayos clínicos con fármacos que prueben disminuir la mortalidad. Por último, se reseñan las medidas terapéuticas no farmacológicas y farmacológicas recomendadas.


Heart failure with preserved and reduced ejection fraction have significant differences. While the latter has had a diagnostic and therapeutic algorithm for years, with guidelines and drugs that improve its prognosis, heart failure with preserved ejection fraction (HFpEF) not only presents difficulties in reaching a diagnosis, but also there are no drugs that have been proven to be effective in reducing mortality. In this review, a broad approach to HFpEF is made, beginning by defining it and distinguishing it from diastolic dysfunction. The gold standard for its invasive diagnosis is described and recently developed non-invasive scores that estimate the probability of having the disease are analyzed. Through the analysis of the frequently associated comorbidities, the pathophysiological mechanisms involved are described. Likewise, the phenotypes proposed to group patients and design clinical trials with drugs that try to reduce mortality are detailed. Finally, the recommended non-pharmacological and pharmacological therapeutic measures are outlined.


A insuficiência cardíaca com fração de ejeção preservada (ICFEp) e reduzida apresentam diferenças marcantes. Enquanto esta última conta com um algoritmo diagnóstico e terapêutico há anos, com diretrizes e medicamentos que melhoram seu prognóstico, a ICFEp não só apresenta dificuldades no diagnóstico, mas nenhum há medicamentos que tenham demonstrado reduzir a mortalidade. Nesta revisão, é feita uma abordagem ampla da ICFEp, começando por defini-la e distinguindo-a da disfunção diastólica. O padrão ouro para seu diagnóstico invasivo é descrito e são analisados os escores não invasivos recentemente desenvolvidos que estimam a probabilidade de ter a doença. Através da análise de comorbidades frequentemente associadas, são descritos os mecanismos fisiopatológicos envolvidos. Da mesma forma, são detalhados os fenótipos propostos para agrupar pacientes e desenhar ensaios clínicos com medicamentos que podem ser mostradas para reduzir a mortalidade. Por fim, são delineadas as medidas terapêuticas não farmacológicas e farmacológicas recomendadas.


Subject(s)
Humans , Heart Failure, Diastolic/physiopathology , Risk Factors , Heart Failure, Diastolic/diagnosis , Heart Failure, Diastolic/therapy
2.
J Card Fail ; 28(5): 789-798, 2022 05.
Article in English | MEDLINE | ID: mdl-35027316

ABSTRACT

BACKGROUND: We are developing a left atrial assist device (LAAD) that is implanted at the mitral position to treat diastolic heart failure (DHF) represented by heart failure with preserved ejection fraction. METHODS: The LAAD was tested at 3 pump speeds on a pulsatile mock loop with a pneumatic pump that simulated DHF conditions by adjusting the diastolic drive. The LAAD was implanted in 6 calves, and the hemodynamics were assessed. In 3 cases, DHF conditions were induced by using a balloon inserted into the left ventricle, and in 2 cases, mitral valve replacement was also performed after the second aortic cross-clamp. RESULTS: DHF conditions were successfully induced in the in vitro study. With LAAD support, cardiac output, aortic pressure and left atrial pressure recovered to normal values, whereas pulsatility was maintained for both in vivo and in vitro studies. Echocardiography showed no left ventricular outflow tract obstruction, and the LAAD was successfully replaced by a mechanical prosthetic valve. CONCLUSIONS: These initial in vitro and in vivo results support our hypothesis that use of the LAAD increases cardiac output and aortic pressure and decreases left atrial pressure, while maintaining arterial pulsatility.


Subject(s)
Heart Failure, Diastolic , Heart Failure , Heart-Assist Devices , Animals , Cattle , Heart Failure, Diastolic/therapy , Hemodynamics , Humans , Stroke Volume
3.
Cardiovasc Res ; 118(1): 53-64, 2022 01 07.
Article in English | MEDLINE | ID: mdl-33620071

ABSTRACT

It is well established that the vasculature plays a crucial role in maintaining oxygen and nutrients supply to the heart. Increasing evidence further suggests that the microcirculation has additional roles in supporting a healthy microenvironment. Heart failure is well known to be associated with changes and functional impairment of the microvasculature. The specific ablation of protective signals in endothelial cells in experimental models is sufficient to induce heart failure. Therefore, restoring a healthy endothelium and microcirculation may be a valuable therapeutic strategy to treat heart failure. This review article will summarize the current understanding of the vascular contribution to heart failure with reduced or preserved ejection fraction. Novel therapeutic approaches including next generation pro-angiogenic therapies and non-coding RNA therapeutics, as well as the targeting of metabolites or metabolic signalling, vascular inflammation and senescence will be discussed.


Subject(s)
Angiogenesis Inducing Agents/therapeutic use , Coronary Vessels/drug effects , Genetic Therapy , Heart Failure, Diastolic/therapy , Heart Failure, Systolic/therapy , Microvessels/drug effects , Neovascularization, Physiologic/drug effects , Vaccines/therapeutic use , Angiogenesis Inducing Agents/adverse effects , Animals , Coronary Circulation/drug effects , Coronary Vessels/metabolism , Coronary Vessels/physiopathology , Genetic Therapy/adverse effects , Heart Failure, Diastolic/genetics , Heart Failure, Diastolic/metabolism , Heart Failure, Diastolic/physiopathology , Heart Failure, Systolic/genetics , Heart Failure, Systolic/metabolism , Heart Failure, Systolic/physiopathology , Humans , Microcirculation/drug effects , Microvessels/metabolism , Microvessels/physiopathology , RNA, Untranslated/genetics , RNA, Untranslated/metabolism , Recovery of Function , Vaccines/adverse effects , Ventricular Function, Left/drug effects
4.
Drugs R D ; 22(1): 25-33, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34826125

ABSTRACT

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is common in elderly people and is increasing in prevalence. No specific treatment for this condition exists. Coenzyme Q10 (CoQ10) is an essential cofactor for energy production, with reduced levels being noted in HF. Previous studies have suggested a possible role for CoQ10 in the treatment of HF. This study examined the effect of CoQ10 supplementation on diastolic function in HFpEF patients. METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled trial including patients aged > 55 years presenting with New York Heart Association class II-IV heart failure symptoms and left ventricular ejection fraction > 50%, with impaired diastolic function. Echocardiography and levels of serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) were performed at baseline and following 4 months of CoQ10 or placebo supplementation. RESULTS: A total of 39 patients were enrolled-19 in the CoQ10 group and 20 in the placebo group. Baseline clinical characteristics were similar between groups, while compliance was high and also similar between the CoQ10 and placebo groups. There was no significant effect of treatment on indices of diastolic function (difference in the lateral E/e' ratio: -0.86 ± 6.57 in the CoQ10 group, +0.18 ± 3.76 in the placebo group; p = 0.561) or on serum NT-proBNP levels (- 72 pg/mL vs. - 42 pg/mL; p = 0.195). CONCLUSIONS: In this pilot trial in elderly patients with HFpEF, treatment with CoQ10 did not significantly affect echocardiographic indices of diastolic function and serum NT-proBNP levels. TRIAL REGISTRATION: This trial was registered in the US National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier: NCT02779634).


Subject(s)
Heart Failure, Diastolic , Ubiquinone/analogs & derivatives , Aged , Double-Blind Method , Heart Failure, Diastolic/physiopathology , Heart Failure, Diastolic/therapy , Humans , Middle Aged , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Prospective Studies , Stroke Volume/drug effects , Ubiquinone/pharmacology , Ubiquinone/therapeutic use , Ventricular Function, Left/drug effects
7.
Cardiovasc Res ; 117(12): 2416-2433, 2021 11 01.
Article in English | MEDLINE | ID: mdl-33483724

ABSTRACT

Heart failure-either with reduced or preserved ejection fraction (HFrEF/HFpEF)-is a clinical syndrome of multifactorial and gender-dependent aetiology, indicating the insufficiency of the heart to pump blood adequately to maintain blood flow to meet the body's needs. Typical symptoms commonly include shortness of breath, excessive fatigue with impaired exercise capacity, and peripheral oedema, thereby alluding to the fact that heart failure is a syndrome that affects multiple organ systems. Patients suffering from progressed heart failure have a very limited life expectancy, lower than that of numerous cancer types. In this position paper, we provide an overview regarding interactions between the heart and other organ systems, the clinical evidence, underlying mechanisms, potential available or yet-to-establish animal models to study such interactions and finally discuss potential new drug interventions to be developed in the future. Our working group suggests that more experimental research is required to understand the individual molecular mechanisms underlying heart failure and reinforces the urgency for tailored therapeutic interventions that target not only the heart but also other related affected organ systems to effectively treat heart failure as a clinical syndrome that affects and involves multiple organs.


Subject(s)
Heart Failure, Diastolic/complications , Heart Failure, Systolic/complications , Heart/physiopathology , Multiple Organ Failure/etiology , Animals , Disease Progression , Functional Status , Heart Failure, Diastolic/mortality , Heart Failure, Diastolic/physiopathology , Heart Failure, Diastolic/therapy , Heart Failure, Systolic/mortality , Heart Failure, Systolic/physiopathology , Heart Failure, Systolic/therapy , Humans , Multiple Organ Failure/mortality , Multiple Organ Failure/physiopathology , Multiple Organ Failure/therapy , Risk Assessment , Risk Factors
8.
Cardiovasc Res ; 117(5): 1325-1338, 2021 04 23.
Article in English | MEDLINE | ID: mdl-32683442

ABSTRACT

AIMS: Heart failure with preserved left ventricular ejection fraction (HFpEF) is a serious health problem worldwide, as no effective therapy is yet available. We have previously demonstrated that our low-intensity pulsed ultrasound (LIPUS) therapy is effective and safe for angina and dementia. In this study, we aimed to examine whether the LIPUS therapy also ameliorates cardiac diastolic dysfunction in mice. METHODS AND RESULTS: Twelve-week-old obese diabetic mice (db/db) and their control littermates (db/+) were treated with either the LIPUS therapy [1.875 MHz, 32 cycles, Ispta (spatial peak temporal average intensity) 117-162 mW/cm2, 0.25 W/cm2] or placebo procedure two times a week for 4 weeks. At 20-week-old, transthoracic echocardiography and invasive haemodynamic analysis showed that cardiac diastolic function parameters, such as e', E/e', end-diastolic pressure-volume relationship, Tau, and dP/dt min, were all deteriorated in placebo-treated db/db mice compared with db/+ mice, while systolic function was preserved. Importantly, these cardiac diastolic function parameters were significantly ameliorated in the LIPUS-treated db/db mice. We also measured the force (F) and intracellular Ca2+ ([Ca2+]i) in trabeculae dissected from ventricles. We found that relaxation time and [Ca2+]i decay (Tau) were prolonged during electrically stimulated twitch contractions in db/db mice, both of which were significantly ameliorated in the LIPUS-treated db/db mice, indicating that the LIPUS therapy also improves relaxation properties at tissue level. Functionally, exercise capacity was also improved in the LIPUS-treated db/db mice. Histologically, db/db mice displayed progressed cardiomyocyte hypertrophy and myocardial interstitial fibrosis, while those changes were significantly suppressed in the LIPUS-treated db/db mice. Mechanistically, western blot showed that the endothelial nitric oxide synthase (eNOS)-nitric oxide (NO)-cGMP-protein kinase G (PKG) pathway and Ca2+-handling molecules were up-regulated in the LIPUS-treated heart. CONCLUSIONS: These results indicate that the LIPUS therapy ameliorates cardiac diastolic dysfunction in db/db mice through improvement of eNOS-NO-cGMP-PKG pathway and cardiomyocyte Ca2+-handling system, suggesting its potential usefulness for the treatment of HFpEF patients.


Subject(s)
Heart Failure, Diastolic/therapy , Stroke Volume , Ultrasonic Therapy , Ultrasonic Waves , Ventricular Dysfunction, Left/therapy , Ventricular Function, Left , Animals , Calcium Signaling , Cyclic GMP-Dependent Protein Kinases/metabolism , Disease Models, Animal , Fibrosis , Heart Failure, Diastolic/genetics , Heart Failure, Diastolic/metabolism , Heart Failure, Diastolic/physiopathology , Isolated Heart Preparation , Mice, Knockout , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Nitric Oxide/metabolism , Nitric Oxide Synthase Type III/metabolism , Receptors, Leptin/genetics , Receptors, Leptin/metabolism , Ventricular Dysfunction, Left/genetics , Ventricular Dysfunction, Left/metabolism , Ventricular Dysfunction, Left/physiopathology
9.
Cardiovasc Res ; 117(4): 999-1014, 2021 03 21.
Article in English | MEDLINE | ID: mdl-32717061

ABSTRACT

Heart failure with preserved ejection fraction (HFpEF) accounts for at least half the cases of heart failure, currently diagnosed. There are several cardiac and non-cardiac manifestations of the syndrome. Structure and function abnormalities can include all four cardiac chambers. The left ventricle has abnormal systolic and diastolic functions which can be examined by invasive and non-invasive measurements. In addition, the left atrium enlarges with abnormal left atrial function, pulmonary hypertension occurs, and the right ventricle can develop hypertrophy, enlargement, and systolic dysfunction. There are a paucity of data on calcium handling in HFpEF patients. Growing literature supports the presence of abnormalities in titin and its phosphorylation, and increased interstitial fibrosis contributing to increased chamber stiffness. A systemic inflammatory state causing reduced myocardial cyclic guanosine monophosphate along with defects in the unfolded protein response have been recently reported. Diagnosis relies on signs and symptoms of heart failure, preserved ejection fraction, and detection of diastolic function abnormalities based on echocardiographic findings and abnormally elevated natriuretic peptide levels or invasive measurements of wedge pressure at rest or with exercise. There are currently two diagnostic algorithms: H2FPEF, and HFA-PEFF with limited data comparing their performance head to head in the same patient population. Despite the growing understanding of the syndrome's pathophysiology, there have been little success in developing specific treatment for patients with HFpEF.


Subject(s)
Cardiac Catheterization , Echocardiography , Heart Failure, Diastolic/diagnosis , Stroke Volume , Ventricular Dysfunction, Left/diagnosis , Ventricular Function, Left , Ventricular Pressure , Animals , Exercise Test , Heart Failure, Diastolic/physiopathology , Heart Failure, Diastolic/therapy , Humans , Models, Cardiovascular , Predictive Value of Tests , Prognosis , Ventricular Dysfunction, Left/physiopathology , Ventricular Dysfunction, Left/therapy
10.
Cell Physiol Biochem ; 54(4): 665-681, 2020 Jul 08.
Article in English | MEDLINE | ID: mdl-32639114

ABSTRACT

BACKGROUND/AIMS: Aortic stenosis-induced chronic pressure overload leads to cardiac dysfunction and congestive heart failure. The pathophysiological mechanisms of the myocardial impairment are multifactorial and include maladaptive ß-adrenergic signaling. Exercise training (ET) has been used as a non-pharmacological therapy for heart failure management. The present study tested the hypothesis that exercise training attenuates diastolic dysfunction through ß-adrenergic signaling preservation. METHODS: Wistar rats were submitted to ascending aortic stenosis (AS) surgery, and after 18 weeks, a moderate aerobic exercise training protocol was performed for ten weeks. RESULTS: ET attenuated diastolic dysfunction, evaluated by echocardiogram and isolated papillary muscle (IPM) assay. Also, ET reduced features of heart failure, cross-sectional cardiomyocyte area, and exercise intolerance, assessed by treadmill exercise testing. The ß2 adrenergic receptor protein expression was increased in AS rats independently of exercise. Interestingly, ET restored the protein levels of phosphorylated phospholamban at Serine 16 and preserved the ß-adrenergic receptor responsiveness as visualized by the lower myocardial compliance decline and time to 50% tension development and relaxation during ß-adrenergic stimulation in the IPM than untrained rats. Additionally, AS rats presented higher levels of TNFα and iNOS, which were attenuated by ET. CONCLUSION: Moderate ET improves exercise tolerance, reduces heart failure features, and attenuates diastolic dysfunction. In the myocardium, ET decreases the cross-sectional area of the cardiomyocyte and preserves the ß-adrenergic responsiveness, which reveals that the adjustments in ß-adrenergic signaling contribute to the amelioration of cardiac dysfunction by mild exercise training in aortic stenosis rats.


Subject(s)
Aortic Stenosis, Supravalvular/metabolism , Heart Failure, Diastolic/therapy , Myocytes, Cardiac/metabolism , Physical Conditioning, Animal/physiology , Receptors, Adrenergic, beta/metabolism , Animals , Aortic Stenosis, Supravalvular/therapy , Calcium-Binding Proteins/metabolism , Echocardiography , Exercise Test , Male , Myocardium/metabolism , Myocytes, Cardiac/physiology , Nitric Oxide Synthase Type II/metabolism , Papillary Muscles/physiology , Phosphorylation , Rats , Rats, Wistar , Receptors, Adrenergic, beta/physiology , Signal Transduction/physiology , Tumor Necrosis Factor-alpha/metabolism
11.
Anaesthesiol Intensive Ther ; 52(3): 237-244, 2020.
Article in English | MEDLINE | ID: mdl-32419432

ABSTRACT

Bedside point-of-care echocardiography is being increasingly incorporated in peri-operative assessment and in intensive care units. Because of availability of tissue Doppler imaging in the modern ultrasound machines there has been an increased interest in research of diastolic function of left ventricle. The diastolic function is crucial for the hemodynamically effective function of the heart. Diastolic dysfunction is a well-established risk factor of the major adverse cardiac events during perioperative period, complications during weaning from ventilator and prognostic factor of mortality in septic shock.


Subject(s)
Anesthesiologists , Heart Failure, Diastolic/therapy , Ventricular Dysfunction, Left/therapy , Echocardiography, Doppler , Electrocardiography , Humans , Point-of-Care Systems
12.
Mayo Clin Proc ; 95(4): 669-675, 2020 04.
Article in English | MEDLINE | ID: mdl-32247341

ABSTRACT

OBJECTIVE: To quantify differences in the diagnosis and treatment of heart failure with preserved ejection fraction (HFpEF) between cardiologists and noncardiologists, who often diagnose and manage HFpEF. METHODS: Cardiologists and noncardiologists (internal medicine, medicine/pediatrics, family medicine, geriatrics) were anonymously surveyed between January 16, 2018, and March 2, 2018, regarding practices related to diagnosing and managing HFpEF at the University of Michigan and Weill Cornell Medical Center. Response data were compared using χ2 analysis. RESULTS: Of 1010 physicians surveyed, 211 completed a significant portion of the survey: 32 cardiologists and 179 noncardiologists. Most noncardiologists were unaware of HFpEF diagnostic guidelines and commonly used left ventricular diastolic dysfunction and natriuretic peptides to diagnose HFpEF. Noncardiologists (32.3%, n=52) were less likely than cardiologists (64.5%, n= 20) to prescribe an aldosterone antagonist for HFpEF (P=.001). Both groups reported similar use of ß-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and exercise programs. Noncardiologists were more likely to refer patients with HFrEF to cardiology (63.1%, n=111) compared with patients with HFpEF (33.5%, n=59; P<.001). Noncardiologists were more likely to discuss prognosis and goals of care with patients with HFrEF (84.4%, n=151) than with patients with HFpEF (65.9%, n=118; P<.001). CONCLUSION: Cardiologists and noncardiologists vary significantly in their HFpEF diagnosis and treatment practices. As diagnostic criteria continue to be evaluated for HFpEF, dissemination of these guidelines to noncardiologists, with an emphasis on the morbidity and mortality associated with HFpEF, is imperative.


Subject(s)
Cardiologists/statistics & numerical data , Heart Failure, Diastolic/diagnosis , Practice Patterns, Physicians'/statistics & numerical data , Heart Failure, Diastolic/physiopathology , Heart Failure, Diastolic/therapy , Humans , Medicine/statistics & numerical data , Referral and Consultation/statistics & numerical data , Stroke Volume , Surveys and Questionnaires
13.
Clin Cardiol ; 43(2): 171-178, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31825134

ABSTRACT

Wild-type transthyretin cardiac amyloidosis (ATTRwt) is now recognized as a common cause of heart failure with preserved ejection fraction (HFpEF). In this review, we aim to describe the unique epidemiologic, pathophysiologic, and clinical features associated with ATTwt cardiac amyloidosis. Compared to other etiologies of HFpEF, ATTRwt cardiac amyloidosis affects almost exclusively older adults, demonstrating a characteristic age-dependent penetrance that impacts both the diagnosis and treatment of the disease. In addition, ATTR cardiac amyloidosis demonstrates a unique pathophysiology in contrast to other etiologies of HFpEF, which results in a characteristic phenotype that can raise suspicion for ATTRwt cardiac amyloid in the appropriate demographic. With these distinguishing features in mind, we aim to describe the specific signs, symptoms, and imaging characteristics associated with ATTRwt cardiac amyloidosis, including the role of nuclear scintigraphy that has essentially eliminated the need for biopsy in most patients with suspected disease. Finally, we review the evidence behind the available therapeutic agents, as well as those under investigation, which will change the way we manage older patients with ATTRwt cardiac amyloidosis in the coming years.


Subject(s)
Aging , Amyloid Neuropathies, Familial , Cardiomyopathies , Heart Failure, Diastolic , Age Factors , Aged , Aged, 80 and over , Amyloid Neuropathies, Familial/diagnostic imaging , Amyloid Neuropathies, Familial/epidemiology , Amyloid Neuropathies, Familial/physiopathology , Amyloid Neuropathies, Familial/therapy , Cardiomyopathies/diagnostic imaging , Cardiomyopathies/epidemiology , Cardiomyopathies/physiopathology , Cardiomyopathies/therapy , Disease Progression , Heart Failure, Diastolic/diagnostic imaging , Heart Failure, Diastolic/epidemiology , Heart Failure, Diastolic/physiopathology , Heart Failure, Diastolic/therapy , Humans , Predictive Value of Tests , Risk Factors , Treatment Outcome
15.
J Am Coll Cardiol ; 73(21): 2705-2718, 2019 06 04.
Article in English | MEDLINE | ID: mdl-31146816

ABSTRACT

BACKGROUND: Patients with chronic kidney disease (CKD) and coincident heart failure with preserved ejection fraction (HFpEF) may constitute a distinct HFpEF phenotype. Osteopontin (OPN) is a biomarker of HFpEF and predictive of disease outcome. We recently reported that OPN blockade reversed hypertension, mitochondrial dysfunction, and kidney failure in Col4a3-/- mice, a model of human Alport syndrome. OBJECTIVES: The purpose of this study was to identify potential OPN targets in biopsies of HF patients, healthy control subjects, and human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs), and to characterize the cardiac phenotype of Col4a3-/- mice, relate this to HFpEF, and investigate possible causative roles for OPN in driving the cardiomyopathy. METHODS: OGDHL mRNA and protein were quantified in myocardial samples from patients with HFpEF, heart failure with reduced ejection fraction, and donor control subjects. OGDHL expression was quantified in hiPS-CMs treated with or without anti-OPN antibody. Cardiac parameters were evaluated in Col4a3-/- mice with and without global OPN knockout or AAV9-mediated delivery of 2-oxoglutarate dehydrogenase-like (Ogdhl) to the heart. RESULTS: OGDHL mRNA and protein displayed abnormal abundances in cardiac biopsies of HFpEF (n = 17) compared with donor control subjects (n = 12; p < 0.01) or heart failure with reduced ejection fraction patients (n = 12; p < 0.05). Blockade of OPN in hiPS-CMs conferred increased OGDHL expression. Col4a3-/- mice demonstrated cardiomyopathy with similarities to HFpEF, including diastolic dysfunction, cardiac hypertrophy and fibrosis, pulmonary edema, and impaired mitochondrial function. The cardiomyopathy was ameliorated by Opn-/- coincident with improved renal function and increased expression of Ogdhl. Heart-specific overexpression of Ogdhl in Col4a3-/- mice also improved cardiac function and cardiomyocyte energy state. CONCLUSIONS: Col4a3-/- mice present a model of HFpEF secondary to CKD wherein OPN and OGDHL are intermediates, and possibly therapeutic targets.


Subject(s)
Disease Models, Animal , Heart Failure, Diastolic/etiology , Ketoglutarate Dehydrogenase Complex/metabolism , Osteopontin/metabolism , Ventricular Dysfunction, Left/etiology , Animals , Autoantigens/genetics , Collagen Type IV/genetics , Fibrosis , Genetic Therapy , Heart Failure, Diastolic/metabolism , Heart Failure, Diastolic/pathology , Heart Failure, Diastolic/therapy , Ketoglutarate Dehydrogenase Complex/genetics , Mice , Mice, Knockout , Mitochondria/metabolism , Myocardium/metabolism , Myocardium/pathology , Nephritis, Hereditary/complications , Osteopontin/genetics , Oxidative Stress , Ventricular Dysfunction, Left/metabolism
17.
ESC Heart Fail ; 6(4): 658-666, 2019 08.
Article in English | MEDLINE | ID: mdl-30963721

ABSTRACT

AIMS: Patients suffering from heart failure with preserved ejection fraction (HFpEF) report similar symptoms and reduction in quality of life to those with reduced ejection fraction but remain largely untreated. We conducted a preliminary evaluation of the acceptance, feasibility, and efficacy of a motivational interviewing (MI) intervention to support elderly patients suffering from HFpEF in maintaining or starting physical activity. METHODS AND RESULTS: At the conclusion of the exercise training in diastolic heart failure parent trial that examined the effects of supervised exercise, patients with HFpEF were offered participation in a two-group pilot study. Based on their preference, consenting patients were assigned to either a 6 month MI intervention group (n = 19) or their physicians' usual care (n = 20). To support participants in increasing and/or maintaining their physical activity, counsellors delivered a mean of 6.5 MI sessions (face to face and via telephone) and also provided a physical activity diary as self-management tool. At baseline and 6 months, we assessed participants' physical activity motivation (Sportbezogene Selbstkonkordanz Scale) and their physical improvements with the 6 min walk test and a cardiopulmonary exercise test. Of the entire sample (N = 39), 46% were female, their mean age was 73, 90% were in New York Heart Association Class II, and the mean ejection fraction was 61.4%. The majority of MI participants rated the intervention as acceptable, 90% perceived MI as helpful in setting specific exercise goals and overcoming barriers concerning physical activity, and 58% considered the physical activity diary as very helpful. Three-quarters of MI participants (79%) reported an increase in their physical activity compared with the previous year. Intervention participants showed a greater increase in median peak VO2 from baseline to 6 months (baseline: 18.4 mL/kg/min; 6 months: 20.4 mL/kg/min) compared with the control group (baseline: 20.0 mL/kg/min; 6 months: 19.2 mL/kg/min; P = 0.015). There was no significant change in motivation on the Sportbezogene Selbstkonkordanz Scale for either group (MI: 1.7 vs. 3, P = 0.55; control: 4.7 vs. 4, P = 0.26) nor did patients show any significant improvements in the 6 min walk test (MI: 549 vs. 540 m, P = 0.80; control: 572 vs. 580 m, P = 0.37). Counsellors rated the implementation of the MI intervention as feasible. CONCLUSIONS: The results from this pilot study suggest that our MI intervention was well accepted by participants and deemed feasible. It also appears to be an effective treatment to increase and maintain physical activity and exercise capacity in patients suffering from HFpEF. Our findings need to be confirmed in a randomized clinical trial with larger and unselected patient cohorts.


Subject(s)
Exercise , Heart Failure, Diastolic , Motivational Interviewing , Aged , Feasibility Studies , Female , Heart Failure, Diastolic/therapy , Humans , Male , Patient Acceptance of Health Care , Pilot Projects , Treatment Outcome
18.
Proteomics Clin Appl ; 13(2): e1800174, 2019 03.
Article in English | MEDLINE | ID: mdl-30632674

ABSTRACT

Diastolic heart failure (DHF) is characterized by slow left ventricular (LV) relaxation, increased LV stiffness, interstitial deposition of collagen, and a modified extracellular matrix proteins. Among Europeans, the frequency of asymptomatic diastolic LV dysfunction (DD) is 25%. This constitutes a large pool of people at high risk of DHF. The goal of this review was to describe the discovery and the initial validation of new multidimensional urinary peptidomic biomarkers (UPB) indicative of DD, mainly consisting of collagen fragments, and to describe a roadmap for their introduction into clinical practice. The availability of new drugs creates a window of opportunity for mounting a randomized clinical trial consolidating the clinical applicability of UPB to screen for DD. If successfully completed, such trial will benefit ≈25% of all people older than 50 years and open a large market for a UPB diagnostic tool and the drug tested. Moreover, sequenced peptides making up UPB will generate novel insights in the pathophysiology of DD and facilitate personalized treatment of patients with DHF for whom prevention came too late. If proven cost-effective, the clinical application of UPB will contribute to the sustainability of health care in aging population in epidemiologic transition.


Subject(s)
Heart Failure, Diastolic/prevention & control , Heart Failure, Diastolic/therapy , Peptides/urine , Precision Medicine/methods , Proteomics/methods , Ventricular Dysfunction, Left/urine , Biomarkers/urine , Heart Failure, Diastolic/physiopathology , Heart Failure, Diastolic/urine , Humans
19.
Heart Fail Clin ; 15(1): 55-64, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30449380

ABSTRACT

Atrial fibrillation often occurs as a cause or consequence of heart failure. Clinical outcomes are worse when atrial fibrillation and heart failure coexist. There are important sex-related differences in the incidence, prevalence, pathophysiology, treatment, and outcomes of these patients. Women with heart failure are at greater risk of developing atrial fibrillation than men, and more women with atrial fibrillation develop heart failure. More women die of atrial fibrillation-related strokes. Despite significant morbidity and mortality, current treatments for women are inadequate. This review explores sex differences in atrial fibrillation and heart failure, emphasizing risk stratification and treatments to improve clinical outcomes.


Subject(s)
Atrial Fibrillation , Heart Failure, Diastolic , Patient Care Management/methods , Atrial Fibrillation/complications , Atrial Fibrillation/epidemiology , Atrial Fibrillation/physiopathology , Atrial Fibrillation/therapy , Female , Heart Failure, Diastolic/epidemiology , Heart Failure, Diastolic/etiology , Heart Failure, Diastolic/physiopathology , Heart Failure, Diastolic/therapy , Humans , Male , Prevalence , Risk Assessment , Sex Factors , Stroke/etiology , Stroke/mortality , Stroke/prevention & control , Treatment Outcome
20.
JACC Heart Fail ; 6(5): 413-420, 2018 05.
Article in English | MEDLINE | ID: mdl-29724363

ABSTRACT

OBJECTIVES: This study sought to determine whether the likelihood of receiving primary intensive care unit (ICU) care by a cardiologist versus a noncardiologist was greater for Caucasians than for African Americans admitted to an ICU for heart failure (HF). The authors further evaluated whether primary ICU care by a cardiologist is associated with higher in-hospital survival, irrespective of race. BACKGROUND: Increasing data demonstrate an association between better HF outcomes and care by a cardiologist. It is unclear if previously noted racial differences in cardiology care persist in an ICU setting. METHODS: Using the Premier database, adult patients admitted to an ICU with a primary discharge diagnosis of HF from 2010 to 2014 were included. Hierarchical logistic regression models were used to determine the association between race and primary ICU care by a cardiologist, adjusting for patient and hospital variables. Cox regression with inverse probability weighting was used to assess the association between cardiology care and in-hospital mortality. RESULTS: Among 104,835 patients (80.3% Caucasians, 19.7% African Americans), Caucasians had higher odds of care by a cardiologist than African Americans (adjusted odds ratio: 1.42; 95% confidence interval: 1.34 to 1.51). Compared with a noncardiologist, primary ICU care by a cardiologist was associated with higher in-hospital survival (adjusted hazard ratio: 1.20, 95% confidence interval: 1.11 to 1.28). The higher likelihood of survival did not differ by patient race (interaction p = 0.32). CONCLUSIONS: Among patients admitted to an ICU for HF, African Americans were less likely than Caucasians to receive primary care by a cardiologist. Primary care by a cardiologist was associated with higher survival for both Caucasians and African Americans.


Subject(s)
Black or African American/statistics & numerical data , Cardiologists/statistics & numerical data , Critical Care/statistics & numerical data , Heart Failure, Diastolic/therapy , Heart Failure, Systolic/therapy , Black or African American/ethnology , Aged , Female , Healthcare Disparities/ethnology , Heart Failure, Diastolic/ethnology , Heart Failure, Diastolic/mortality , Heart Failure, Systolic/ethnology , Heart Failure, Systolic/mortality , Hospital Mortality , Hospitalization/statistics & numerical data , Hospitals, Rural/statistics & numerical data , Hospitals, Urban/statistics & numerical data , Humans , Intensive Care Units/statistics & numerical data , Male , Middle Aged , Retrospective Studies , United States/epidemiology
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