Left ventricular noncompaction in patients with heart failure with preserved ejection fraction characterized by multimodality imaging

Abstract Background Left ventricular non-compaction (LVNC) is associated with increased risk of heart failure (HF). If LVNC or hyper-trabeculation in HF with preserved ejection fraction (HFpEF) is an adaptive or stand-alone condition that contribute to generation of HF is not clearly understood yet. Aim To describe LV functional and structural parameters in HFpEF with LVNC by comparison with HFpEF without LVNC. Methods We assessed 42 patients with HFpEF, 21 with LVNC (61±9 yrs) and 21 without LVNC, age and risk factors matched (LVC), by NTproBNP, 2D echocardiography (2DE), speckle-tracking (STE), and cardiac magnetic resonance (CMR) (Figure 1). LVNC diagnosis was based on Petersen and Jacquier criteria, by the NC/C ratio and the percentage of NC myocardium. Two gradients were calculated: a base to apex gradient (LVbase-apex) and an endo-epicardial gradient (LVendo-epi). LV mass, LV end-diastolic volume (LVEDV), and T1 mapping with extracellular volume (ECV) were measured, while mean value of native T1 for apical segments (apicalT1), mean value of ECV for apical (apical ECV), and basal segments (basal ECV), and gradient between them (ECV base-apex) were calculated. Results In the LVNC, mean NC/C ratio was 2.9±0.5mm and the percentage of NC myocardium 24.4±8.8%. NTproBNP was higher in LVNC group (294±282 vs. 163±71 pg/ml, p=0.047). Functional findings were consistent with the structural changes from CMR. LVNC patients have higher native T1 in the apical segments (Table). ECV was globally expanded in LVNC compared to LVC (p=0.002) suggesting diffuse fibrosis, but the difference between groups was more relevant for apical ECV (29.6±3.9% vs 25.1±2.8%, p<0.001), with a higher ECV base-apex gradient in LVNC group. ECV base-apex gradient was negatively correlated with the percentage of NC myocardium (p=0.003, R=0.64). Conclusion Patients with HFpEF with LVNC have more fibrosis, with more severe changes in the apical segments on CMR than HFpEF without NC. They have also significantly decreased apical deformation, lower base to apex deformation gradient and lower transmural deformation gradient, due to non-compaction itself, which involves the endocardial layer. These findings suggests that NC in HFpEF is an independent condition rather than an adaptive one. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Ministry of Research and Innovation, CNCS-UEFISCDI.

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Left ventricular fibrosis and hypertrophy are associated with mortality in heart failure with preserved ejection fraction

Scientific Reports ◽

10.1038/s41598-020-79729-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Pankaj Garg ◽

Hosamadin Assadi ◽

Rachel Jones ◽

Wei Bin Chan ◽

Peter Metherall ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

T1 Mapping ◽

Left Ventricular ◽

Preserved Ejection Fraction ◽

Native T1 ◽

Lv Mass ◽

All Cause Mortality ◽

Ventricular Fibrosis

AbstractCardiac magnetic resonance (CMR) is emerging as an important tool in the assessment of heart failure with preserved ejection fraction (HFpEF). This study sought to investigate the prognostic value of multiparametric CMR, including left and right heart volumetric assessment, native T1-mapping and LGE in HFpEF. In this retrospective study, we identified patients with HFpEF who have undergone CMR. CMR protocol included: cines, native T1-mapping and late gadolinium enhancement (LGE). The mean follow-up period was 3.2 ± 2.4 years. We identified 86 patients with HFpEF who had CMR. Of the 86 patients (85% hypertensive; 61% males; 14% cardiac amyloidosis), 27 (31%) patients died during the follow up period. From all the CMR metrics, LV mass (area under curve [AUC] 0.66, SE 0.07, 95% CI 0.54–0.76, p = 0.02), LGE fibrosis (AUC 0.59, SE 0.15, 95% CI 0.41–0.75, p = 0.03) and native T1-values (AUC 0.76, SE 0.09, 95% CI 0.58–0.88, p < 0.01) were the strongest predictors of all-cause mortality. The optimum thresholds for these were: LV mass > 133.24 g (hazard ratio [HR] 1.58, 95% CI 1.1–2.2, p < 0.01); LGE-fibrosis > 34.86% (HR 1.77, 95% CI 1.1–2.8, p = 0.01) and native T1 > 1056.42 ms (HR 2.36, 95% CI 0.9–6.4, p = 0.07). In multivariate cox regression, CMR score model comprising these three variables independently predicted mortality in HFpEF when compared to NTproBNP (HR 4 vs HR 1.65). In non-amyloid HFpEF cases, only native T1 > 1056.42 ms demonstrated higher mortality (AUC 0.833, p < 0.01). In patients with HFpEF, multiparametric CMR aids prognostication. Our results show that left ventricular fibrosis and hypertrophy quantified by CMR are associated with all-cause mortality in patients with HFpEF.

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Serum uric acid, influence of sacubitril/valsartan, and cardiovascular outcomes in heart failure with preserved ejection fraction: PARAGON-HF

European Heart Journal ◽

10.1093/ehjci/ehaa946.1066 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

S Selvaraj ◽

B.L Claggett ◽

D.V Veldhuisen ◽

I.S Anand ◽

B Pieske ◽

...

Keyword(s):

Heart Failure ◽

Uric Acid ◽

Ejection Fraction ◽

Serum Uric Acid ◽

Primary Outcome ◽

Adverse Outcomes ◽

Funding Source ◽

Preserved Ejection Fraction ◽

Private Company ◽

Increased Risk

Abstract Background Serum uric acid (SUA) is a biomarker of several pathobiologies relevant to the pathogenesis of heart failure with preserved ejection fraction (HFpEF), though by itself may also worsen outcomes. In HF with reduced EF, SUA is independently associated with adverse outcomes and sacubitril/valsartan reduces SUA compared to enalapril. These effects in HFpEF have not been delineated. Purpose To determine the prognostic value of SUA, relationship of change in SUA to quality of life and outcomes, and influence of sacubitril/valsartan on SUA in HFpEF. Methods We analyzed 4,795 participants from the Prospective Comparison of ARNI with ARB Global Outcomes in HF with Preserved Ejection Fraction (PARAGON-HF) trial. We related baseline hyperuricemia to the primary outcome (CV death and total HF hospitalization), its components, myocardial infarction or stroke, and a renal composite outcome. At the 4-month visit, the relationship between SUA change and Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OSS) and several biomarkers including N-terminal pro-B-type natriuretic peptide (NT-proBNP) were also assessed. We simultaneously adjusted for baseline and time-updated SUA to determine whether lowering SUA was associated with clinical benefit. Results Average age was 73±8 years and 52% were women. After multivariable adjustment, hyperuricemia was associated with increased risk for most outcomes (primary outcome HR 1.61, 95% CI 1.37, 1.90, Fig 1A). The treatment effect of sacubitril/valsartan for the primary outcome was not modified by baseline SUA (interaction p=0.11). Sacubitril/valsartan reduced SUA −0.38 mg/dL (95% CI: −0.45, −0.31) compared with valsartan (Fig 1B), with greater effect in those with baseline hyperuricemia (−0.50 mg/dL) (interaction p=0.013). Change in SUA was independently and inversely associated with change in KCCQ-OSS (p=0.019) and eGFR (p<0.001), but not NT-proBNP (p=0.52). Time-updated SUA was a stronger predictor of adverse outcomes over baseline SUA. Conclusions SUA independently predicts adverse outcomes in HFpEF. Sacubitril/valsartan significantly reduces SUA compared to valsartan, an effect that was stronger in those with higher baseline SUA, and reducing SUA was associated with improved outcomes. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Novartis

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Validation of the HFA-PEFF- and H2FPEF score in Japanese patients with heart failure with preserved ejection fraction

European Heart Journal ◽

10.1093/ehjci/ehaa946.0998 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

K Iwakura ◽

T Onishi ◽

M Okada ◽

K Inoue ◽

Y Koyama ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Global Longitudinal Strain ◽

Japanese Patients ◽

Mean Value ◽

Diagnostic Tools ◽

Funding Source ◽

Preserved Ejection Fraction ◽

Private Company ◽

Patients With Heart Failure

Abstract Background Diagnosing heart failure with preserved ejection fraction (HFpEF) still remains challenging, and simple and reliable diagnostic tools have been required. Recently, novel and evidence-based diagnostic algorithms for HFpEF were proposed, such as H2FPEF score (Circulation. 2018) and HFA-PEFF score (Eur Heart J 2019), and their accuracy was validated in the outside patient group. However, there are regional and ethnic variations in patient characteristics of HFpEF, particularly between Western and Asian countries, and it is not elucidated whether these diagnostic scores are useful in Asian population. Purpose To investigate the validity of the HFA-PEFF- and H2FPEF score in Japanese patients with HFpEF. Methods We calculated H2FPEF score and the second step of HFA-PEFF score among the registered patients in the PURSUIT-HFpEF (Prospective, Multicenter, Observational Study of Patients with Heart Failure with Preserved Ejection Fraction) study, which is a multicenter registration of patients hospitalized for HFpEF. The obtained scores were compared with the scores of the HFpEF cohort in the previous validation studies. We followed the study patients for median of 360 days (IQR 237–630 days) to observe the major adverse cardiovascular events (MACE; composite of death, heart failure hospitalization and stroke). Results We enrolled 757 patients hospitalized for HFpEF between June 2016 and August 2019 for the present study. H2FPEF score was obtained in 588 (77.7%) patients among them. Compared with the HFpEF cohorts in the previously reported sub-analysis of TOPCAT trial, the PURSUIT-HFpEF cohort had lower mean value of HFpEF score (4.0±1.8 points vs. 6.0±2.0 points in Americans or 5.3±1.9 points in Russians). It had significantly higher proportion (40.3%, p<0.001) of patients in the low likelihood of HFpEF category (0–3 points) than the TOPCAT cohorts (8.0% in Americans and 19.6% in Russians). HFA-PEFF score was obtained in 615 (81.2%) patients, though global longitudinal strain was not available. The mean value of HFA-PEFF score was 5.0±0.8, and all patients had ≥2 points. The proportion of patients in the high likelihood of HFpEF category (5–6 points) was 88.3%, which was significantly higher (p<0.001) than those of the HFpEF cohort from Europe and USA in the previous validation study (Eur J Heart Fail 2019). There was no correlation between H2FPEF score and HFA-PEFF score (R=0.06, p=0.14). Cox proportional hazard model selected HFA-PEFF score as a significant predictor for MACE during follow-up period, whereas H2PEF score was not selected. Kaplan-Meier survival analysis demonstrated that patients with 6 points of HFA-PEFF score had higher incidence rate of MACE than those with ≤5 points (p=0.002). Conclusion The HFA-PEFF score could be more useful for the diagnosis and risk stratification for HFpEF than the H2PEF score in the Japanese cohort. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Roche Diagnostics K.K.; Fuji Film Toyama Chemical Co. Ltd.

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Obesity accelerates cardiac senescence in heart failure with preserved ejection fraction

European Heart Journal ◽

10.1093/ehjci/ehaa946.0871 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

F.H Verbrugge ◽

Y.N.V Reddy ◽

S Kapa ◽

B.A Borlaug

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Diastolic Dysfunction ◽

Left Ventricular ◽

P Value ◽

Funding Source ◽

Obese Patients ◽

Preserved Ejection Fraction ◽

Ecg Analysis ◽

The Impact

Abstract Background Diastolic reserve decreases with aging. A recently developed artificial intelligence (AI) algorithm can predict age based on 12-lead electrocardiogram (ECG) analysis. Purpose This study aims to use a validated AI algorithm to assess cardiac senescence and investigate the impact of obesity on cardiac aging in heart failure with preserved ejection fraction (HFpEF). Methods This retrospective cohort study includes 403 patients with HFpEF, admitted for treatment with intravenous diuretics. ECG age was assessed by a convolutional neural network as previously validated. Patients were stratified according to the presence of obesity (body mass index >30 kg/m2) and ECG age was compared between groups. The relationship between ECG versus calendar age and structural/functional alterations on echocardiography, as well as the risk of atrial fibrillation (AF) development, was evaluated. Results In 253 (63%) obese patients with HFpEF, calendar age was 8 years younger compared with their non-obese counterparts, but ECG age was only 3 years younger. ECG minus calendar age was higher in obese patients (P-value <0.001; figure) and correlated moderately strong with weight, fat free, and fat mass (r=0.35–0.41; P-value <0.001). Older ECG age was correlated with worse diastolic function, but not with left ventricular afterload (table). Calendar age correlated less strongly with diastolic dysfunction (table). ECG age did predict AF development, independently of calendar age, gender, and presence of obesity [HR (95% CI) = 1.31 (1.06–1.63) per 5-year; P-value=0.015]. Conclusions Obesity accelerates cardiac senescence in HFpEF as reflected by more pronounced diastolic dysfunction and a higher AF risk, which was identified from ECG analysis by a validated AI algorithm. Figure 1 Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Belgian American Educational Foundation (B.A.E.F.); Special Research Fund (BOF) of Hasselt University (Hasselt, Belgium).

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Impact of Interatrial Shunts on Invasive Hemodynamics and Exercise Tolerance in Patients With Heart Failure

Journal of the American Heart Association ◽

10.1161/jaha.120.016760 ◽

2020 ◽

Vol 9 (17) ◽

Author(s):

Jan M. Griffin ◽

Barry A. Borlaug ◽

Jan Komtebedde ◽

Sheldon E. Litwin ◽

Sanjiv J. Shah ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Exercise Tolerance ◽

Right Heart Failure ◽

Left Ventricular ◽

Preserved Ejection Fraction ◽

Increased Risk ◽

Patients With Heart Failure ◽

Alternative Means ◽

Interatrial Shunt

Approximately 50% of patients with heart failure have preserved ejection fraction. Although a wide variety of conditions cause or contribute to heart failure with preserved ejection fraction, elevated left ventricular filling pressures, particularly during exercise, are common to all causes. Acute elevation in left‐sided filling pressures promotes lung congestion and symptoms of dyspnea, while chronic elevations often lead to pulmonary vascular remodeling, right heart failure, and increased risk of mortality. Pharmacologic therapies, including neurohormonal modulation and drugs that modify the nitric oxide/cyclic GMP‐protein kinase G pathway have thus far been limited in reducing symptoms or improving outcomes in patients with heart failure with preserved ejection fraction. Hence, alternative means of reducing the detrimental rise in left‐sided heart pressures are being explored. One proposed method of achieving this is to create an interatrial shunt, thus unloading the left heart at rest and during exercise. Currently available studies have shown 3‐ to 5‐mm Hg decreases of pulmonary capillary wedge pressure during exercise despite increased workload. The mechanisms underlying the hemodynamic changes are just starting to be understood. In this review we summarize results of recent studies aimed at elucidating the potential mechanisms of improved hemodynamics during exercise tolerance following interatrial shunt implantation and the current interatrial shunt devices under investigation.

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The clinical and prognostic value of late Gadolinium enhancement imaging in heart failure with mid-range and preserved ejection fraction

Heart and Vessels ◽

10.1007/s00380-021-01910-2 ◽

2021 ◽

Author(s):

Gijs van Woerden ◽

Dirk J. van Veldhuisen ◽

Thomas M. Gorter ◽

Tineke P. Willems ◽

Vanessa P. M. van Empel ◽

...

Keyword(s):

Heart Failure ◽

Late Gadolinium Enhancement ◽

Ejection Fraction ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Preserved Ejection Fraction ◽

Regression Analyses ◽

Gadolinium Enhancement ◽

Increased Risk ◽

All Cause Mortality

AbstractHeart failure (HF) with mid-range or preserved ejection fraction (HFmrEF; HFpEF) is a heterogeneous disorder that could benefit from strategies to identify subpopulations at increased risk. We tested the hypothesis that HFmrEF and HFpEF patients with myocardial scars detected with late gadolinium enhancement (LGE) are at increased risk for all-cause mortality. Symptomatic HF patients with left ventricular ejection fraction (LVEF) > 40%, who underwent cardiac magnetic resonance (CMR) imaging were included. The presence of myocardial LGE lesions was visually assessed. T1 mapping was performed to calculate extracellular volume (ECV). Multivariable logistic regression analyses were used to determine associations between clinical characteristics and LGE. Cox regression analyses were used to assess the association between LGE and all-cause mortality. A total of 110 consecutive patients were included (mean age 71 ± 10 years, 49% women, median N-terminal brain natriuretic peptide (NT-proBNP) 1259 pg/ml). LGE lesions were detected in 37 (34%) patients. Previous myocardial infarction and increased LV mass index were strong and independent predictors for the presence of LGE (odds ratio 6.32, 95% confidence interval (CI) 2.07–19.31, p = 0.001 and 1.68 (1.03–2.73), p = 0.04, respectively). ECV was increased in patients with LGE lesions compared to those without (28.6 vs. 26.6%, p = 0.04). The presence of LGE lesions was associated with a fivefold increase in the incidence of all-cause mortality (hazards ratio 5.3, CI 1.5–18.1, p = 0.009), independent of age, sex, New York Heart Association (NYHA) functional class, NT-proBNP, LGE mass and LVEF. Myocardial scarring on CMR is associated with increased mortality in HF patients with LVEF > 40% and may aid in selecting a subpopulation at increased risk.

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Elevated exercise blood pressure in middle-aged women is associated with altered left ventricular and vascular stiffness

Journal of Applied Physiology ◽

10.1152/japplphysiol.00458.2019 ◽

2020 ◽

Vol 128 (5) ◽

pp. 1123-1129 ◽

Cited By ~ 1

Author(s):

Satyam Sarma ◽

Erin Howden ◽

Graeme Carrick-Ranson ◽

Justin Lawley ◽

Christopher Hearon ◽

...

Keyword(s):

Heart Failure ◽

Blood Pressure ◽

Ejection Fraction ◽

Screening Tool ◽

Left Ventricular ◽

Vascular Stiffness ◽

Preserved Ejection Fraction ◽

Middle Aged ◽

Increased Risk ◽

Exercise Blood Pressure

Women are at increased risk for heart failure with preserved ejection fraction (HFpEF) largely due to higher prevalence of arterial and cardiac stiffening. We were able to identify several subclinical markers of early (stages A and B) HFpEF pathophysiology largely on the basis of exercise blood pressure (BP) response in otherwise healthy middle-aged women. Exercise BP response may be an inexpensive screening tool to identify women at highest risk for developing future HFpEF.

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Atrial fibrillation and risk of incident heart failure with reduced versus preserved ejection fraction

Heart ◽

10.1136/heartjnl-2021-319122 ◽

2021 ◽

pp. heartjnl-2021-319122

Author(s):

Charles D Nicoli ◽

Wesley T O’Neal ◽

Emily B Levitan ◽

Matthew J Singleton ◽

Suzanne E Judd ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Ejection Fraction ◽

Racial Differences ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Preserved Ejection Fraction ◽

Ventricular Ejection Fraction ◽

Increased Risk ◽

Significant Difference

ObjectiveAssociations between atrial fibrillation (AF) and heart failure (HF) have been established. We compared the extent to which AF is associated with each primary subtype of HF, with reduced (HFrEF) versus preserved ejection fraction (HFpEF).MethodsWe included 25 787 participants free of baseline HF from the REGARDS (REasons for Geographic And Racial Differences in Stroke) cohort. Baseline AF was ascertained from ECG and self-reported history of physician diagnosis. Incident HF events were determined from physician-adjudicated review of hospitalisation medical records and HF deaths. Based on left ventricular ejection fraction (LVEF) at the time of HF event, HFrEF, HFpEF, and mid-range HF were defined as LVEF <40%, ≥50% and 40%–49%, respectively. Multivariable Cox proportional-hazards models examined the association between AF and HF. The Lunn-McNeil method was used to compare associations of AF with incident HFrEF versus HFpEF.ResultsOver a median of 9 years of follow-up, 1109 HF events occurred (356 HFpEF, 388 HFrEF, 77 mid-range and 288 unclassified). In a model adjusted for sociodemographics, cardiovascular risk factors, and incident coronary heart disease, AF was associated with increased risk of all HF events (HR 1.67, 95% CI 1.38 to 2.01). The associations of AF with HFrEF versus HFpEF events did not differ significantly (HR 1.87 (95% CI 1.38 to 2.54) and HR 1.65 (95% CI 1.20 to 2.28), respectively; p value for difference=0.581). These associations were consistent in sex and race subgroups.ConclusionsAF is associated with both HFrEF and HFpEF events, with no significant difference in the strength of association among these subtypes.

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Prevalence and prognostic significance of heart failure with preserved ejection fraction in systemic sclerosis

Future Cardiology ◽

10.2217/fca-2020-0238 ◽

2021 ◽

Author(s):

Marta Fontes Oliveira ◽

Ana Leonor Rei ◽

Maria Isilda Oliveira ◽

Isabel Almeida ◽

Mário Santos

Keyword(s):

Heart Failure ◽

Systemic Sclerosis ◽

Ejection Fraction ◽

Statistical Significance ◽

Prognostic Significance ◽

Left Ventricular ◽

Preserved Ejection Fraction ◽

Increased Risk ◽

Atrial Enlargement

Aim: Heart failure with preserved ejection fraction (HFpEF) is a clinically relevant complication of systemic sclerosis (SSc). We aimed to examine the prevalence, correlates and prognostic significance of HFpEF in an SSc population. Materials & methods: HFpEF was defined by the presence of exertional dyspnoea, abnormal cardiac structure (left ventricular hypertrophy or left atrial enlargement) and NT-proBN (>125 pg/ml). Results: Of the 155 studied patients, 27% had HFpEF criteria. These patients were older, had more cardiovascular risk factors, and were more likely to have atrial fibrillation or interstitial lung disease. Conclusion: Over a median follow-up of 9 years, SSc patients with HFpEF had a 3.4-fold increased risk of dying (HR: 3.37, 95% CI: 1.21–9.31), although this association has lost statistical significance after adjusting for age. On the contrary, NT-proBNP was an independent predictor of a worse prognosis.

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Prevalence of microvascular dysfunction and association with clinical outcomes in heart failure with preserved ejection fraction

European Heart Journal ◽

10.1093/ehjci/ehaa946.0253 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

J Arnold ◽

P Kanagala ◽

C.A Budgeon ◽

M.J Jerosch-Herold ◽

A.S Singh ◽

...

Keyword(s):

Heart Failure ◽

Myocardial Perfusion ◽

Ejection Fraction ◽

Clinical Outcomes ◽

Microvascular Dysfunction ◽

Left Ventricular ◽

Microvascular Function ◽

Funding Source ◽

Preserved Ejection Fraction ◽

Coronary Microvascular Function

Abstract Introduction Heart failure with preserved ejection fraction (HFpEF) accounts for approximately 50% of symptomatic heart failure. A recently proposed paradigm for the pathophysiology of HFpEF postulates a central inflammatory aetiology with coronary microvascular function at its core. However, the pathophysiological and clinical significance of microvascular dysfunction in HFpEF remains uncertain. Purpose Utilising cardiovascular magnetic resonance (CMR), we sought to (1) quantify coronary microvascular function, (2) evaluate the impact of microvascular dysfunction and fibrosis on long-term clinical outcomes and (3) examine the relationship between myocardial perfusion and fibrosis. Methods In a prospective, observational study, 147 subjects (104 HFpEF without a prior history or CMR evidence of coronary artery disease, and 43 asymptomatic controls) underwent multiparametric CMR, comprising left ventricular volumetric assessment, absolute quantitation of myocardial blood flow [MBF] during adenosine stress (140mcg/kg/min) and at rest, and evaluation of diffuse myocardial fibrosis (extracellular volume [ECV]). The primary endpoint was the composite of death or hospitalisation with heart failure. Results 104 HFpEF patients (mean age 73±9 years, mean ejection fraction 56%) and 43 controls (mean age 73±5 years, mean ejection fraction 58%) were studied. There was no significant difference in resting MBF (1.10±0.42ml/min/g in HFpEF subjects vs 1.00±0.38 ml/min/g in controls, p=0.23), though hyperaemic MBF was lower in HFpEF subjects (1.66±0.68 ml/min/g vs 1.97±0.59 ml/min/g, p=0.01). Myocardial perfusion reserve [MPR] was also lower in HFpEF subjects (1.73±0.75 vs 2.22±0.76; p<0.01). Microvascular dysfunction (defined as MPR<2.0) was present in 70% of HFpEF patients (versus 33% of controls, p<0.01). During median follow-up of 3.4 years, there were 46 composite events. MPR was predictive of clinical outcome (one unit increase – hazard ratio [HR] 0.57; 95% CI 0.35–0.92; p=0.02), as was ECV (one standard deviation [SD] increase – HR 1.65; 95% CI 1.14–2.39; p=0.01). However, there was no significant linear correlation between MPR and diffuse fibrosis (r<0.01, p=0.99). Conclusion Microvascular dysfunction is highly prevalent in HFpEF and is associated with adverse clinical outcomes. The lack of correlation between abnormal myocardial perfusion and fibrosis challenges the assertion of a direct causal link between these entities. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): NIHR, BHF

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