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BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) frequently co-exist. There is a limited understanding on whether this coexistence is associated with distinct alterations in myocardial remodelling and mechanics. We aimed to determine if patients with atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) represent a distinct phenotype. METHODS: In this secondary analysis of adults with HFpEF (NCT03050593), participants were comprehensively phenotyped with stress cardiac MRI, echocardiography and plasma fibroinflammatory biomarkers, and were followed for the composite endpoint (HF hospitalisation or death) at a median of 8.5 years. Those with AF were compared to sinus rhythm (SR) and unsupervised cluster analysis was performed to explore possible phenotypes. RESULTS: 136 subjects were included (SR = 75, AF = 61). The AF group was older (76 ± 8 vs. 70 ± 10 years) with less diabetes (36% vs. 61%) compared to the SR group and had higher left atrial (LA) volumes (61 ± 30 vs. 39 ± 15 mL/m2, p < 0.001), lower LA ejection fraction (EF) (31 ± 15 vs. 51 ± 12%, p < 0.001), worse left ventricular (LV) systolic function (LVEF 63 ± 8 vs. 68 ± 8%, p = 0.002; global longitudinal strain 13.6 ± 2.9 vs. 14.7 ± 2.4%, p = 0.003) but higher LV peak early diastolic strain rates (0.73 ± 0.28 vs. 0.53 ± 0.17 1/s, p < 0.001). The AF group had higher levels of syndecan-1, matrix metalloproteinase-2, proBNP, angiopoietin-2 and pentraxin-3, but lower level of interleukin-8. No difference in clinical outcomes was observed between the groups. Three distinct clusters were identified with the poorest outcomes (Log-rank p = 0.029) in cluster 2 (hypertensive and fibroinflammatory) which had equal representation of SR and AF. CONCLUSIONS: Presence of AF in HFpEF is associated with cardiac structural and functional changes together with altered expression of several fibro-inflammatory biomarkers. Distinct phenotypes exist in HFpEF which may have differing clinical outcomes.
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Fibrilación Atrial , Insuficiencia Cardíaca , Imágenes de Resonancia Magnética Multiparamétrica , Humanos , Adulto , Volumen Sistólico , Metaloproteinasa 2 de la Matriz , Función Ventricular Izquierda , Biomarcadores , Fenotipo , PronósticoRESUMEN
Late, repetitive or chronic remote ischaemic conditioning (CRIC) is a potential cardioprotective strategy against adverse remodelling following ST-segment elevation myocardial infarction (STEMI). In the randomised Daily Remote Ischaemic Conditioning Following Acute Myocardial Infarction (DREAM) trial, CRIC following primary percutaneous coronary intervention (P-PCI) did not improve global left ventricular (LV) systolic function. A post-hoc analysis was performed to determine whether CRIC improved regional strain. All 73 patients completing the original trial were studied (38 receiving 4 weeks' daily CRIC, 35 controls receiving sham conditioning). Patients underwent cardiovascular magnetic resonance at baseline (5-7 days post-STEMI) and after 4 months, with assessment of LV systolic function, infarct size and strain (longitudinal/circumferential, in infarct-related and remote territories). At both timepoints, there were no significant between-group differences in global indices (LV ejection fraction, infarct size, longitudinal/circumferential strain). However, regional analysis revealed a significant improvement in longitudinal strain in the infarcted segments of the CRIC group (from - 16.2 ± 5.2 at baseline to - 18.7 ± 6.3 at follow up, p = 0.0006) but not in corresponding segments of the control group (from - 15.5 ± 4.0 to - 15.2 ± 4.7, p = 0.81; for change: - 2.5 ± 3.6 versus + 0.3 ± 5.6, respectively, p = 0.027). In remote territories, there was a lower increment in subendocardial circumferential strain in the CRIC group than in controls (- 1.2 ± 4.4 versus - 2.5 ± 4.0, p = 0.038). In summary, CRIC following P-PCI for STEMI is associated with improved longitudinal strain in infarct-related segments, and an attenuated increase in circumferential strain in remote segments. Further work is needed to establish whether these changes may translate into a reduced incidence of adverse remodelling and clinical events. Clinical Trial Registration: http://clinicaltrials.gov/show/NCT01664611 .
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Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Humanos , Intervención Coronaria Percutánea/efectos adversos , Infarto del Miocardio con Elevación del ST/terapia , Volumen Sistólico , Resultado del Tratamiento , Función Ventricular IzquierdaRESUMEN
AIMS: To investigate the relationship between fibro-inflammatory biomarkers and cardiovascular structure/function in people with Type 2 Diabetes (T2D) compared to healthy controls and the effect of two lifestyle interventions in T2D. METHODS: Data were derived from the DIASTOLIC randomised controlled trial (RCT) and includes a comparison between those with T2D and the matched healthy volunteers recruited at baseline. Adults with T2D without cardiovascular disease (CVD) were randomized to a 12-week intervention either: (1) exercise training, (2) a low-energy (â¼810 kcal/day) meal-replacement plan (MRP) or (3) standard care. Principal Component and Fisher's linear discriminant analysis were used to investigate the relationships between MRI acquired cardiovascular outcomes and fibro-inflammatory biomarkers in cases versus controls and pre- and post-intervention in T2D. RESULTS: At baseline, 83 people with T2D (mean age 50.5 ± 6.4; 58% male) and 36 healthy controls (mean age 48.6 ± 6.2; 53% male) were compared and 76 people with T2D completed the RCT for pre- post-analysis. Compared to healthy controls, subjects with T2D had adverse cardiovascular remodelling and a fibro-inflammatory profile (20 differentially expressed biomarkers). The 3D data visualisations showed almost complete separation between healthy controls and those with T2D, and a marked shift towards healthy controls following the MRP (15 biomarkers significantly changed) but not exercise training. CONCLUSIONS: Fibro-inflammatory pathways and cardiovascular structure/function are adversely altered before the onset of symptomatic CVD in middle-aged adults with T2D. The MRP improved the fibro-inflammatory profile of people with T2D towards a more healthy status. Long-term studies are required to assess whether these changes lead to continued reverse cardiac remodelling and prevent CVD.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Adulto , Biomarcadores , Restricción Calórica , Enfermedades Cardiovasculares/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Ejercicio Físico , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVES: To determine the test-retest reproducibility and observer variability of CMR-derived LA function, using (i) LA strain (LAS) and strain rate (LASR), and (ii) LA volumes (LAV) and emptying fraction (LAEF). METHODS: Sixty participants with and without cardiovascular disease (aortic stenosis (AS) (n = 16), type 2 diabetes (T2D) (n = 28), end-stage renal disease on haemodialysis (n = 10) and healthy volunteers (n = 6)) underwent two separate CMR scans 7-14 days apart. LAS and LASR, corresponding to LA reservoir, conduit and contractile booster-pump function, were assessed using Feature Tracking software (QStrain v2.0). LAEF was calculated using the biplane area length method (QMass v8.1). Both were assessed using 4- and 2-chamber long-axis standard steady-state free precession cine images, and average values were calculated. Intra- and inter-observer variabilities were assessed in 10 randomly selected participants. RESULTS: The test-retest reproducibility was moderate to poor for all strain and strain rate parameters. Overall, strain and strain rate corresponding to reservoir phase (LAS_r, LASR_r) were the most reproducible, yielding the smallest coefficient of variance (CoV) (29.9% for LAS_r, 28.9% for LASR_r). The test-retest reproducibility for LAVs and LAEF was good: LAVmax CoV = 19.6% ICC = 0.89, LAVmin CoV = 27.0% ICC = 0.89 and total LAEF CoV = 15.6% ICC = 0.78. The inter- and intra-observer variabilities were good for all parameters except for conduit function. CONCLUSION: The test-retest reproducibility of LA strain and strain rate assessment by CMR utilising Feature Tracking is moderate to poor across disease states, whereas LA volume and emptying fraction are more reproducible on CMR. Further improvements in LA strain quantification are needed before widespread clinical application. KEY POINTS: ⢠LA strain and strain rate assessment using Feature Tracking on CMR has moderate to poor test-retest reproducibility across disease states. ⢠The test-retest reproducibility for the biplane method of assessing LA function is better than strain assessment, with lower coefficient of variances and narrower limits of agreement on Bland-Altman plots. ⢠Biplane LA volumetric measurement also has better intra- and inter-observer variability compared to strain assessment.
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Función del Atrio Izquierdo , Diabetes Mellitus Tipo 2 , Atrios Cardíacos/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Imagen por Resonancia Cinemagnética , Variaciones Dependientes del Observador , Valor Predictivo de las Pruebas , Reproducibilidad de los ResultadosRESUMEN
OBJECTIVES: Aortic stenosis (AS) is characterised by a long and variable asymptomatic course. Our objective was to use cardiovascular magnetic resonance imaging (MRI) to assess progression of adverse remodeling in asymptomatic AS. METHODS: Participants from the PRIMID-AS study, a prospective, multi-centre observational study of asymptomatic patients with moderate to severe AS, who remained asymptomatic at 12 months, were invited to undergo a repeat cardiac MRI. RESULTS: Forty-three participants with moderate-severe AS (mean age 64.4 ± 14.8 years, 83.4% male, aortic valve area index 0.54 ± 0.15 cm2/m2) were included. There was small but significant increase in indexed left ventricular (LV) (90.7 ± 22.0 to 94.5 ± 23.1 ml/m2, p = 0.007) and left atrial volumes (52.9 ± 11.3 to 58.6 ± 13.6 ml/m2, p < 0.001), with a decrease in systolic (LV ejection fraction 57.9 ± 4.6 to 55.6 ± 4.1%, p = 0.001) and diastolic (longitudinal diastolic strain rate 1.06 ± 0.2 to 0.99 ± 0.2 1/s, p = 0.026) function, but no overall change in LV mass or mass/volume. Late gadolinium enhancement increased (2.02 to 4.26 g, p < 0.001) but markers of diffuse interstitial fibrosis did not change significantly (extracellular volume index 12.9 [11.4, 17.0] ml/m2 to 13.3 [11.1, 15.1] ml/m2, p = 0.689). There was also a significant increase in the levels of NT-proBNP (43.6 [13.45, 137.08] pg/ml to 53.4 [19.14, 202.20] pg/ml, p = 0.001). CONCLUSIONS: There is progression in cardiac remodeling with increasing scar burden even in asymptomatic AS. Given the lack of reversibility of LGE post-AVR and its association with long-term mortality post-AVR, this suggests the potential need for earlier intervention, before the accumulation of LGE, to improve the long-term outcomes in AS. KEY POINTS: ⢠Current guidelines recommend waiting until symptom onset before valve replacement in severe AS. ⢠MRI showed clear progression in cardiac remodeling over 12 months in asymptomatic patients with AS, with near doubling in LGE. ⢠This highlights the need for potentially earlier intervention or better risk stratification in AS.
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Estenosis de la Válvula Aórtica , Medios de Contraste , Anciano , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Ecocardiografía , Femenino , Gadolinio , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Función Ventricular Izquierda , Remodelación VentricularRESUMEN
BACKGROUND: We demonstrated that physiologist-led stress echocardiography (PLSE) is feasible for coronary artery disease (CAD) assessment. We sought to extend our work by assessing its accuracy and prognostic value. METHODS: Retrospective study of 898 subjects undergoing PLSE (n=393) or cardiologist-led stress echocardiography (CLSE) (n=505) for CAD assessment using exercise or dobutamine. For accuracy assessment, the primary outcome was the ability of stress echocardiography to identify significant CAD on invasive coronary angiography (ICA). Incidence of 24-month non-fatal MI, total and cardiac mortality, revascularisation and combined major adverse cardiac events (MACE) were assessed. RESULTS: Demographics, comorbidities, CAD predictors, CAD pre-test probability and cardiac medications were matched between the PLSE and CLSE groups. PLSE had high sensitivity, specificity, positive and negative predictive value and accuracy (85%, 74%, 69%, 88%, 78% respectively). PLSE accuracy measures were similar and non-inferior to CLSE. There was a similar incidence of individual and combined outcomes in PLSE and CLSE subjects. Negative stress echocardiography conferred a comparably low incidence of non-fatal MI (PLSE 1.4% vs. CLSE 0.9%, p=0.464), cardiac mortality (0.6% vs. 0.0%, p=0.277) and MACE (6.8% vs. 3.1%, p=0.404). CONCLUSION: This is the first study of the accuracy compared with gold standard of ICA, and prognostic value of PLSE CAD assessment. PLSE demonstrates high and non-inferior accuracy compared with CLSE for CAD assessment. Negative PLSE and CLSE confer a similarly very low incidence of cardiac outcomes, confirming for the first time the important prognostic value of PLSE.
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Enfermedad de la Arteria Coronaria , Ecocardiografía de Estrés , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Prueba de Esfuerzo , Humanos , Pronóstico , Estudios RetrospectivosRESUMEN
INTRODUCTION: Tenascin-C is a marker of interstitial fibrosis. We assessed whether plasma Tenascin-C differed between heart failure with preserved ejection fraction (HFpEF) and asymptomatic controls and related to clinical outcomes. MATERIALS AND METHODS: Prospective, observational study of 172 age- and sex-matched subjects (HFpEF n = 130; controls n = 42, age 73 ± 9, males 50%) who underwent phenotyping with 20 plasma biomarkers, echocardiography, cardiac MRI and 6-minute-walk-testing. The primary endpoint was the composite of all-cause death/HF hospitalisation. RESULTS: Tenascin-C was higher in HFpEF compared to controls (13.7 [10.8-17.3] vs (11.1 [8.9-12.9] ng/ml, p < 0.0001). Tenascin-C correlated positively with markers of clinical severity (NYHA, E/E', BNP) and plasma biomarkers reflecting interstitial fibrosis (ST-2, Galectin-3, GDF-15, TIMP-1, TIMP-4, MMP-2, MMP-3, MMP-7, MMP-8), cardiomyocyte stress (BNP, NTpro-ANP), inflammation (MPO, hs-CRP, TNFR-1, IL6) and renal dysfunction (urea, cystatin-C, NGAL); p < 0.05 for all. During follow-up (median 1428 days), there were 61 composite events (21 deaths, 40 HF hospitalizations). In multivariable Cox regression analysis, Tenascin-C (adjusted hazard ratio [HR] 1.755, 95% confidence interval [CI] 1.305-2.360; p < 0.0001) and indexed extracellular volume (HR 1.465, CI 1.019-2.106; p = 0.039) were independently associated with adverse outcomes. CONCLUSIONS: In HFpEF, plasma Tenascin-C is higher compared to age- and sex-matched controls and a strong predictor of adverse outcomes. Trial registration: ClinicalTrials.gov: NCT03050593.
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Biomarcadores/sangre , Insuficiencia Cardíaca/sangre , Pronóstico , Tenascina/sangre , Adulto , Anciano , Femenino , Galectina 3/sangre , Factor 15 de Diferenciación de Crecimiento/sangre , Insuficiencia Cardíaca/patología , Humanos , Masculino , Persona de Mediana Edad , Volumen Sistólico/genética , Inhibidor Tisular de Metaloproteinasa-1/sangreRESUMEN
BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a poorly characterized condition. We aimed to phenotype patients with HFpEF using multiparametric stress cardiovascular magnetic resonance imaging (CMR) and to assess the relationship to clinical outcomes. METHODS: One hundred and fifty four patients (51% male, mean age 72 ± 10 years) with a diagnosis of HFpEF underwent transthoracic echocardiography and CMR during a single study visit. The CMR protocol comprised cine, stress/rest perfusion and late gadolinium enhancement imaging on a 3T scanner. Follow-up outcome data (death and heart failure hospitalization) were captured after a minimum of 6 months. RESULTS: CMR detected previously undiagnosed pathology in 42 patients (27%), who had similar baseline characteristics to those without a new diagnosis. These diagnoses consisted of: coronary artery disease (n = 20, including 14 with 'silent' infarction), microvascular dysfunction (n = 11), probable or definite hypertrophic cardiomyopathy (n = 10) and constrictive pericarditis (n = 5). Four patients had dual pathology. During follow-up (median 623 days), patients with a new CMR diagnosis were at higher risk of adverse outcome for the composite endpoint (log rank test: p = 0.047). In multivariate Cox proportional hazards analysis, a new CMR diagnosis was the strongest independent predictor of adverse outcome (hazard ratio: 1.92; 95% CI: 1.07 to 3.45; p = 0.03). CONCLUSIONS: CMR diagnosed new significant pathology in 27% of patients with HFpEF. These patients were at increased risk of death and heart failure hospitalization. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03050593 . Retrospectively registered; Date of registration: February 06, 2017.
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Ensayos Clínicos como Asunto/métodos , Insuficiencia Cardíaca/diagnóstico por imagen , Imagen por Resonancia Magnética , Imagen de Perfusión Miocárdica/métodos , Volumen Sistólico , Función Ventricular Izquierda , Adenosina/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Causas de Muerte , Medios de Contraste/administración & dosificación , Circulación Coronaria , Ecocardiografía , Femenino , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/fisiopatología , Humanos , Imagen por Resonancia Cinemagnética , Masculino , Persona de Mediana Edad , Compuestos Organometálicos/administración & dosificación , Valor Predictivo de las Pruebas , Pronóstico , Factores de Tiempo , Vasodilatadores/administración & dosificaciónRESUMEN
PURPOSE: To determine the interstudy reproducibility of myocardial strain and peak early-diastolic strain rate (PEDSR) measurement on cardiovascular magnetic resonance imaging (MRI) assessed with feature tracking (FT) and tagging, in patients with aortic stenosis (AS). MATERIALS AND METHODS: Cardiac MRI was performed twice (1-14 days apart) in 18 patients (8 at 1.5 Tesla [T], 10 at 3T) with moderate-severe AS. Circumferential peak systolic strain (PSS) and PEDSR were measured in all patients. Longitudinal PSS and PEDSR were assessed using FT in all patients, and tagging in the 3T sub-group. RESULTS: PSS was higher with FT than tagging (21.0 ± 1.9% versus 17.0 ± 3.4% at 1.5T, 21.4 ± 4.0% versus 17.7 ± 3.0% at 3T, P < 0.05), as was PEDSR (1.3 ± 0.3 s(-1) versus 1.0 ± 0.3 s(-1) , P = 0.10 at 1.5T and 1.3 ± 0.4 s(-1) versus 0.8 ± 0.3 s(-1) , P < 0.05 at 3T). The reproducibility of PSS was excellent with FT (coefficient of variation [CoV] 9-10%) and good with tagging at 1.5T (13-19%). Reproducibility of circumferential PEDSR was best at 1.5T when only basal/mid slices were included (CoV 12%), but moderate to poor at 3T (29-35%). Reproducibility of longitudinal strain was good with FT (10-16%) but moderate for PEDSR (â¼30%). CONCLUSION: In patients with AS, FT consistently produces higher values compared with tagging. The interstudy reproducibility of PSS is excellent with FT and good with tagging. The reproducibility of circumferential PEDSR at 1.5T is good when only basal and mid slices are used.
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Algoritmos , Estenosis de la Válvula Aórtica/fisiopatología , Interpretación de Imagen Asistida por Computador/métodos , Imagen por Resonancia Cinemagnética/métodos , Reconocimiento de Normas Patrones Automatizadas/métodos , Disfunción Ventricular Izquierda/fisiopatología , Anciano , Estenosis de la Válvula Aórtica/complicaciones , Estenosis de la Válvula Aórtica/patología , Diástole , Módulo de Elasticidad , Diagnóstico por Imagen de Elasticidad/métodos , Femenino , Humanos , Aumento de la Imagen/métodos , Masculino , Variaciones Dependientes del Observador , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Resistencia al Corte , Estrés Mecánico , Volumen Sistólico , Disfunción Ventricular Izquierda/etiología , Disfunción Ventricular Izquierda/patologíaRESUMEN
Heart failure with preserved ejection fraction (HFpEF) currently accounts for approximately half of all new heart failure cases in the community. HFpEF is closely associated with chronic lifestyle-related diseases, such as obesity and type 2 diabetes, and clinical outcomes are worse in those with than without comorbidities. HFpEF is pathophysiologically distinct from heart failure with reduced ejection fraction, which may explain, in part, the disparity of treatment options available between the two heart failure phenotypes. The mechanisms underlying HFpEF are complex, with coronary microvascular dysfunction (MVD) being proposed as a potential key driver in its pathophysiology. In this review, the authors highlight the evidence implicating MVD in HFpEF pathophysiology, the diagnostic approaches for identifying MVD (both invasive and non-invasive) and the prevalence and prognostic significance of MVD.
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PURPOSE: Cardiac autonomic neuropathy (CAN) is a serious complication of type 1 and type 2 diabetes and is independently associated with major cardiovascular events, morbidity, and mortality. This narrative review examines the epidemiology, pathophysiology, and management and identifies areas of future research to address the challenge posed by CAN. METHODS: We conducted a comprehensive literature search using a range of sources, including the electronic databases PubMed Central, Google Scholar, OVID, and Open Athens, to search for studies on CAN, diabetes mellitus, lifestyle intervention, and cardiovascular risk. We set inclusion criteria to consider review articles or original research published in peer-reviewed journals that examined CAN in diabetes. FINDINGS: Epidemiologic data indicate a varied prevalence of CAN in type 1 and 2 diabetes, with prevalences of 17% to 73%) depending on clinical and demographic factors. Indeed, duration of diabetes and hyperglycemia are the strongest risk factors for CAN development in type 1 diabetes. However, in type 2 diabetes, multifactorial risk factors, including obesity, hypertension, and hyperlipidemia, are associated with the development of CAN. Insulin resistance, which underpins type 2 diabetes and metabolic syndrome, has a direct role in the pathogenesis of CAN. Lifestyle interventions, including dietary measures and tailored exercise programs, have been beneficial in improving cardiac autonomic function primarily measured through heart rate variability. In addition, weight loss through bariatric surgery also improves heart rate variability and may prevent or reduce CAN progression in people living with obesity and concomitant type 2 diabetes. For optimization in type 2 diabetes, both lifestyle and targeted pharmacologic interventions are required to achieve glycemic/metabolic targets, and weight loss is required to prevent or reverse early CAN or prevent the progression to definite and severe CAN. IMPLICATIONS: The focused use of diagnostic testing for CAN, including cardiac autonomic reflex testing in those at high risk of CAN, will enable earlier diagnosis. This testing will allow timely interventions at a reversible stage. Future research should examine targeted early diagnostic testing with subsequent intervention with a combination of lifestyle measures and newer pharmacotherapeutics (eg, sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists), which have produced significant cardiovascular benefit in diabetes.
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Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 1/terapia , Sistema Nervioso Autónomo , Obesidad/epidemiología , Pérdida de PesoRESUMEN
Heart failure (HF) is a major cause of morbidity and mortality worldwide. Current classifications of HF categorize patients with a left ventricular ejection fraction of 50% or greater as HF with preserved ejection fraction or HFpEF. Echocardiography is the first line imaging modality in assessing diastolic function given its practicality, low cost and the utilization of Doppler imaging. However, the last decade has seen cardiac magnetic resonance (CMR) emerge as a valuable test for the sometimes challenging diagnosis of HFpEF. The unique ability of CMR for myocardial tissue characterization coupled with high resolution imaging provides additional information to echocardiography that may help in phenotyping HFpEF and provide prognostication for patients with HF. The precision and accuracy of CMR underlies its use in clinical trials for the assessment of novel and repurposed drugs in HFpEF. Importantly, CMR has powerful diagnostic utility in differentiating acquired and inherited heart muscle diseases presenting as HFpEF such as Fabry disease and amyloidosis with specific treatment options to reverse or halt disease progression. This state of the art review will outline established CMR techniques such as transmitral velocities and strain imaging of the left ventricle and left atrium in assessing diastolic function and their clinical application to HFpEF. Furthermore, it will include a discussion on novel methods and future developments such as stress CMR and MR spectroscopy to assess myocardial energetics, which show promise in unraveling the mechanisms behind HFpEF that may provide targets for much needed therapeutic interventions.
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BACKGROUND: The pathophysiological and clinical significance of microvascular dysfunction (MVD) in patients with heart failure with preserved ejection fraction (HFpEF) remains uncertain. OBJECTIVES: The aim of this study was to use cardiovascular magnetic resonance to: 1) quantify coronary microvascular function; 2) examine the relationship between perfusion and fibrosis; and 3) evaluate the impact of MVD and fibrosis on long-term clinical outcomes. METHODS: In a prospective, observational study, patients with HFpEF and control subjects underwent multiparametric cardiovascular magnetic resonance (comprising assessment of left ventricular volumetry, perfusion, and fibrosis [focal by late gadolinium enhancement and diffuse by extracellular volume]). The primary endpoint was the composite of death or hospitalization with heart failure. RESULTS: One hundred and one patients with HFpEF (mean age 73 ± 9 years, mean ejection fraction 56% ± 5%) and 43 control subjects (mean age 73 ± 5 years, mean ejection fraction 58% ± 5%) were studied. Myocardial perfusion reserve (MPR) was lower in patients with HFpEF versus control subjects (1.74 ± 0.76 vs 2.22 ± 0.76; P = 0.001). MVD (defined as MPR <2.0) was present in 70% of patients with HFpEF (vs 48% of control subjects; P = 0.014). There was no significant linear correlation between MPR and diffuse fibrosis (r = -0.10; P = 0.473) and no difference in MPR between those with and without focal fibrosis (mean difference -0.03; 95% CI: -0.37 to 0.30). In the HFpEF group, during median follow-up of 3.1 years, there were 45 composite events. MPR was independently predictive of clinical outcome following adjustment for clinical, blood, and imaging parameters (1 SD increase: HR: 0.673 [95% CI: 0.463 to 0.978; P = 0.038]; HR: 0.694 [95% CI: 0.491 to 0.982; P = 0.039]; and HR: 0.690 [95% CI: 0.489 to 0.973; P = 0.034], respectively). CONCLUSIONS: MVD is highly prevalent among patients with HFpEF and is an independent predictor of prognosis. The lack of correlation between MVD and fibrosis may challenge the assertion of a direct causal link between these entities. (Developing Imaging and Plasma Biomarkers in Describing Heart Failure With Preserved Ejection Fraction [DIAMONDHFpEF]; NCT03050593).
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Insuficiencia Cardíaca , Anciano , Anciano de 80 o más Años , Medios de Contraste , Fibrosis , Gadolinio , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/epidemiología , Humanos , Imagen por Resonancia Cinemagnética/métodos , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Prevalencia , Pronóstico , Estudios Prospectivos , Volumen Sistólico , Función Ventricular IzquierdaRESUMEN
The left atrium (LA) plays a vital role in maintaining normal cardiac function. LA volume and function have been utilised as important imaging biomarkers, with their prognostic value demonstrated in multiple cardiac conditions. More recently, there has been a sharp increase in the number of publications utilising LA strain by echocardiography and cardiac magnetic resonance (CMR) imaging. However, little is known about its prognostic value or reproducibility as a technique. In this review, we aim to highlight the conventional and novel imaging techniques available for LA assessment, using echocardiography and CMR, their role as an imaging biomarker in cardiovascular disease, the reproducibility of the techniques and the current limitations to their clinical application. We identify a need for further standardisation of techniques, with establishment of 'normal' cut-offs before routine clinical application can be made.
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Función del Atrio Izquierdo , Enfermedades Cardiovasculares , Biomarcadores , Enfermedades Cardiovasculares/diagnóstico por imagen , Atrios Cardíacos/diagnóstico por imagen , Humanos , Imagen por Resonancia Cinemagnética , Valor Predictivo de las Pruebas , Reproducibilidad de los ResultadosRESUMEN
We aimed to determine the prognostic association between cardiac autonomic neuropathy (CAN) and cardiovascular disease events (CVE) and mortality in type 1 and type 2 diabetes through a systematic review and meta-analysis. This systematic review and meta-analysis was registered with PROSPERO (CRD42020216305) and was conducted with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodological criteria. CAN was defined on the basis of 1 (early/possible CAN) or ≥2 (definite CAN) positive autonomic function tests as per the Toronto Consensus guidelines. Studies included those with prospective CVE or mortality data. Methodological variables/risk of bias were assessed using ROBINS-I (Risk Of Bias In Non-randomized Studies - of Interventions) and RoB-2 (Risk-Of-Bias tool for randomized trials) appraisal tools. Electronic database searches yielded 18 467 articles; 84 articles were screened full-text, 26 articles fulfilled the inclusion criteria for quantitative synthesis. Sixteen studies from patients with (n=2875) and without (n=11 722) CAN demonstrated a pooled relative risk (RR) of 3.16 (95%CI 2.42 to 4.13; p<0.0001) of future CVE in favour of CAN. Nineteen studies provided all-cause mortality data from patients with (n=3679) and without (n=12 420) CAN, with a pooled RR of 3.17 (95%CI 2.11 to 4.78; p<0.0001) in favour of CAN. The risk of both future CVE and mortality was higher in type 1 compared with type 2 diabetes and with a definite CAN (vs possible CAN) diagnosis. Three studies were considered to have risk of serious bias. This study confirms the significant association between CAN and CVE and all-cause mortality. The implementation of population-based CAN screening will identify a subgroup with disproportionately higher cardiovascular and mortality risk that will allow for earlier targeted intervention.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Neuropatías Diabéticas , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/mortalidad , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Neuropatías Diabéticas/complicaciones , Humanos , Tamizaje Masivo , PronósticoRESUMEN
AIMS: The aim of the study was to assess the association of P-selectin with outcomes in heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: This is a prospective, observational study of 130 HFpEF patients who underwent clinical profiling, blood sampling, 6 min walk testing, Minnesota Living with Heart Failure Questionnaire evaluation, echocardiography, cardiovascular magnetic resonance imaging, calculation of the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk scores, and blinded plasma P-selectin measurement. Patients were followed up for the endpoint of all-cause mortality. The HFpEF subgroup with higher P-selectin levels [overall median 26 372, inter-quartile range (19 360-34 889) pg/mL] was associated with lower age, higher heart rate, less prevalent atrial fibrillation, more frequent current smoking status, and lower right ventricular end-diastolic volumes. During follow-up (median 1428 days), there were 38 deaths. Following maximal sensitivity and specificity receiver operating characteristic curve analysis, P-selectin levels above 35 506 pg/mL were associated with greater risk of all-cause mortality [hazard ratio (HR) 2.700; 95% confidence interval (CI) 1.416-5.146; log-rank P = 0.002]. Following multivariable Cox proportional hazards regression analysis and when added to MAGGIC scores, only P-selectin (adjusted HR 1.707; 95% CI 1.099-2.650; P < 0.017) and myocardial infarction detected by cardiovascular magnetic resonance imaging (HR 2.377; 95% CI 1.114-5.075; P < 0.025) remained significant predictors. In a final model comprising all three parameters, only P-selectin (HR 1.447; 95% CI 1.130-1.853; P < 0.003) and MAGGIC scores (HR 1.555; 95% CI 1.136-2.129; P < 0.006) remained independent predictors of death. Adding P-selectin (0.618, P = 0.035) improved the area under the receiver operating characteristic curve for mortality prediction for MAGGIC scores (0.647, P = 0.009) to 0.710, P < 0.0001. CONCLUSIONS: Plasma P-selectin is an independent predictor of mortality and provides incremental prognostic information beyond MAGGIC scores in HFpEF.
Asunto(s)
Insuficiencia Cardíaca , Ecocardiografía , Humanos , Metaanálisis como Asunto , Selectina-P , Estudios Prospectivos , Volumen SistólicoRESUMEN
There is a paucity of data characterizing right ventricular performance in heart failure with preserved ejection fraction (HFpEF) using the gold standard of cardiovascular magnetic resonance imaging (CMR). We aimed to assess the proportion of right ventricular systolic dysfunction (RVD) in HFpEF and the relation to clinical outcomes. As part of a single-centre, prospective, observational study, 183 subjects (135 HFpEF, and 48 age- and sex-matched controls) underwent extensive characterization with CMR. transthoracic echocardiography, blood sampling and six-minute walk testing. Patients were followed for the composite endpoint of death or HF hospitalization. RVD (defined as right ventricular ejection fraction < 47%) controls was present in 19% of HFpEF. Patients with RVD presented more frequently with lower systolic blood pressure, atrial fibrillation, radiographic evidence of pulmonary congestion and raised cardiothoracic ratio and larger right ventricular volumes. During median follow-up of 1429 days, 47% (n = 64) of HFpEF subjects experienced the composite endpoint of death (n = 22) or HF hospitalization (n = 42). RVD was associated with an increased risk of composite events (Log-Rank p = 0.001). In multivariable Cox regression analysis, RVD was an independent predictor of adverse outcomes (adjusted Hazard Ratio [HR] 3.946, 95% CI 1.878-8.290, p = 0.0001) along with indexed extracellular volume (HR 1.742, CI 1.176-2.579, p = 0.006) and E/E' (HR 1.745, CI 1.230-2.477, p = 0.002). RVD as assessed by CMR is prevalent in nearly one-fifth of HFpEF patients and is independently associated with death and/or hospitalization with HF.The trial was registered retrospectively on ClinicalTrials.gov (Identifier: NCT03050593). The date of registration was February 06, 2017.
Asunto(s)
Insuficiencia Cardíaca/epidemiología , Volumen Sistólico , Disfunción Ventricular Derecha/epidemiología , Función Ventricular Derecha , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Ecocardiografía , Inglaterra/epidemiología , Femenino , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/fisiopatología , Humanos , Imagen por Resonancia Cinemagnética , Masculino , Persona de Mediana Edad , Admisión del Paciente , Valor Predictivo de las Pruebas , Prevalencia , Pronóstico , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Disfunción Ventricular Derecha/diagnóstico por imagen , Disfunción Ventricular Derecha/mortalidad , Disfunción Ventricular Derecha/fisiopatologíaRESUMEN
Functionally uni-leaflet mitral valves are extremely rare. In severe cases, they are considered incompatible with life beyond the neonatal period. We present a case series of three adults with almost complete absence of the posterior mitral valve leaflet and who are asymptomatic, with no more than mild mitral regurgitation. We believe that this is the first reported instance of such findings in a single family.
Asunto(s)
Cardiopatías Congénitas/diagnóstico por imagen , Cardiopatías Congénitas/genética , Válvula Mitral/anomalías , Válvula Mitral/diagnóstico por imagen , Adolescente , Femenino , Humanos , Persona de Mediana Edad , Madres , Linaje , Pronóstico , Medición de Riesgo , Hermanos , UltrasonografíaRESUMEN
The aim of this study was to determine whether left atrial ejection fraction (LAEF) quantified with cardiovascular magnetic resonance (CMR) was different between heart failure with preserved ejection fraction (HFpEF) and controls, and its relation to prognosis. As part of our single-centre, prospective, observational study, 188 subjects (HFpEF n = 140, controls n = 48) underwent phenotyping with contrast-enhanced CMR, transthoracic echocardiography, blood sampling and six-minute walk testing. LAEF was calculated using the biplane method. Atrial fibrillation (AF) was present in 43 (31%) of HFpEF subjects. Overall, LAEF (%) was lower in HFpEF patients inclusive of AF (32 ± 16) or those in sinus rhythm alone (41 ± 12) compared to controls (51 ± 11), p < 0.0001. LAEF correlated inversely with maximal and minimal left atrial volumes indexed (r = - 0.602, r = - 0.762), and plasma N-terminal pro-atrial natriuretic peptide (r = - 0.367); p < 0.0001. During median follow-up (1429 days), there were 67 composite events of all-cause death or hospitalization for heart failure (22 deaths, 45 HF hospitalizations) in HFpEF. Lower LAEF (below median) was associated with an increased risk of composite endpoints (Log-Rank: all p = 0.028; sinus p = 0.036). In multivariable Cox regression analysis, LAEF (adjusted hazard ratio [HR] 0.767, 95% confidence interval [CI] 0.591-0.996; p = 0.047) and indexed extracellular volume (HR 1.422, CI 1.015-1.992; p = 0.041) were the only parameters that remained significant when added to a base prognostic model comprising age, prior HF hospitalization, diastolic blood pressure, lung disease, NYHA, six-minute-walk-test-distance, haemoglobin, creatinine and B-type natriuretic peptide. CMR-derived LAEF is lower in HFpEF compared to healthy controls and is a strong prognostic biomarker.