Diastolic Stress Research Articles

Clinical parameters and cardiovascular risk factors related to heart failure with preserved ejection fraction: a comparative analysis between HFA-PEFF and H2FPEF Scores

Abstract Background Heart failure with preserved ejection fraction (HFpEF) diagnosis remains challenging, since several mechanisms (diastolic and systolic reserve abnormalities, chronotropic incompetence, ventricular or vascular stiffening, atrial dysfunction, pulmonary hypertension, impaired vasodilation, endothelial dysfunction, energetic abnormalities and autonomic dysfunction) play different roles in HFpEF development. European Society of Cardiology HF guidelines recently suggested a stepwise non-invasive diagnostic approach consisting of three steps: the first is clinical, the second includes echocardiographic and laboratory data (natriuretic peptides), named HFA-PEEF score, and finally, in case of inconclusive findings, diastolic stress echocardiography is recommended. On the other hand, in United States, another multiparametric score, named H2FPEF, has been proposed for HFpEF diagnosis, and including, in addition to echocardiographic parameters, also clinical data; thereby more applicable in the outpatient clinical arena. Purpose Whether there is a clinical overlap between the two scores (HFA-PEEF and H2FPEF) as well as whether the addition of clinical data to the HFA-PEEF could improve its ability to identify different HFpEF phenotypes is still an open issue and these were the aims of our study. Methods HFA-PEEF and H2FPEF scores were systematically applied on 1,156 consecutive subjects with preserved ejection fraction who undergone cardiovascular evaluation at the Cardiovascular Prevention Center of Fondazione Don Gnocchi & University of Parma. All subjects underwent cardiovascular risk assessment followed by echocardiography and cardiopulmonary exercise testing; due to the outpatient (non-acute) setting of the evaluation, natriuretic peptides assay was not performed. Clinical data and cardiovascular risk factors data were compared between different groups of HFpEF risk. Results According to H2FPEF score, low risk (<40%) of HFpEF was found in 659 (57%), moderate in 300 (26%) and high (>75%) in 197 (17%); according to HFA-PEEF score, 675 (58%) had 0 or 1 point, 253 (22%) had 2 points and 230 (20%) had 3 or 4 points (moderate-to-high risk). Patients with higher HFA-PEEF score were older (p<0.001), had higher prevalence of HTN (p<0.001), diabetes (p<0.001), obesity (p<0.001), sedentary lifestyle (p<0.001), AF (p<0.001) and CCS (p<0.001) (figure 1). More specifically, AF was associated to a 6.3-fold higher risk (p<0.001) of high (3–4) HFA-PEEF Score, age >75 years to a 4.6-fold higher risk, HTN to a 3.6-fold higher risk (p<0.001), CCS to a 3.3-fold higher risk (p<0.001), obesity to a 2.2-fold higher risk (p<0.001), diabetes to a 1.9-fold higher risk (p<0.001) and sedentary to a 1.7-fold higher risk (p=0.001). Conclusions Although HFA-PEEF score does not include clinical data, patients with older age, atrial fibrillation, hypertension, hypertensive heart, diabetes, sedentary lifestyle and chronic coronary syndrome show a higher ESC risk of HFpEF. Funding Acknowledgement Type of funding sources: None.

Cardiopulmonary response to exercise and heart failure with preserved ejection fraction risk: a comparative analysis of HFA-PEFF and H2FPEF scores

Abstract Background Exercise intolerance evaluation in Heart failure with preserved ejection fraction (HFpEF) remains challenging, since several mechanisms (diastolic and systolic reserve abnormalities, low chronotropic reserve (CR), ventricular or vascular stiffening, atrial dysfunction, pulmonary hypertension, endothelial dysfunction, energetic abnormalities and autonomic dysfunction) play different roles. European Society of Cardiology HF guidelines recently suggested a stepwise non-invasive HFpEF diagnostic approach consisting of three steps: clinical, echocardiographic and laboratory data (natriuretic peptides), named HFA-PEEF Score, and finally, in case of inconclusive findings, diastolic stress echocardiography data. Cardiopulmonary exercise testing (CPET) may represent a promising further non-invasive diagnostic tool in HFpEF evaluation since allow to assess the presence of reduced functional capacity as well as to differentiate between cardiovascular, ventilatory or peripheral causes. Purpose Whether increased risk of HFpEF is associated with different and specific cardiopulmonary responses to exercise is still an open issue and this was the aim of our study. Methods 1.156 consecutive subjects with preserved ejection fraction undergoing cardiovascular evaluation at the Cardiovascular Prevention Center of Fondazione Don Gnocchi & University of Parma were enrolled. All subjects underwent cardiovascular evaluation and echocardiography, HFA-PEEF and H2FPEF Score assessment and cardiopulmonary exercise testing. Different cardiopulmonary response to exercise were compared between different groups of HFpEF risk. Results According to HFA-PEEF Score, 675 (58%) had 0 or 1 point, 253 (22%) had 2 points and 230 (20%) had 3 or 4 points (moderate-to-high risk). Patients with both higher HFA-PEEF and H2FPEF Score showed lower functional capacity, expressed as low peak V02 (p<0.001) associated with lower oxygen pulse (V02/HR) (p<0.001), cardiac output (CO) at peak (p<0.001), CR (p<0.001), ventilatory efficiency (expressed as VE/VC02 slope) (p<0.001) and oxygen uptake extraction (OUES) (p<0.001). Moreover, higher H2FPEF Score patients showed lower stroke volume (SV) at peak (p<0.001), while high HFA-PEEF score was not associated to SV at peak (Table 1 and Figure 1). More specifically, the presence of reduced cardiovascular efficiency (V02/Watt Slope <7) was associated to a 2.2-fold higher risk of HFpEF (p=0.003), impaired ventilator efficiency (VE/VCO2 Slope >35) to a 2.4-fold higher risk (p<0.001), reduced CR (<70%) 4.3-fold higher risk (p<0.001). Conclusions Different degrees HFpEF risk, estimated using both HFA-PEEF and H2FPEF score, are associated with different cardiopulmonary responses to exercise. High HFpEF risk patients show low functional capacity, cardiovascular and ventilator efficiency due to lower cardiac output at peak, despite preserved ejection fraction, associated to lower chronotropic response to exercise. Funding Acknowledgement Type of funding sources: None.

Analysis of diastolic left ventricular wall shear stress in normal people of different age groups.

BackgroundDiastolic wall shear stress (WSS), assessed by using vector flow mapping (VFM), is the result of the interaction between the blood flow and the ventricular wall. This study aimed to evaluate the trend of left ventricular (LV) WSS in normal subjects.Methods and resultsA total of 371 healthy volunteers were recruited and divided into four age groups (group I: 18–30 years; group II: 31–43 years; group III: 44–56 years; group IV: 57–70 years). LV WSS of different age groups was measured at each diastolic phase (P1: isovolumic diastolic period, P2: rapid filling period, P3: slow filling period, and P4:atrial contraction period) to evaluate the change trend of LV WSS. In each age group, LV WSS coincided with a trend of increasing-decreasing-increasing during P1–P4 (P < 0.05). Besides, among groups I, II, III, and IV, WSS of anterolateral, inferoseptal, and anteroseptal in P1 and WSS of inferolateral, inferoseptal, and anteroseptal in P4 all showed an increasing trend with age (P < 0.05). Regarding sex differences, women had greater diastolic WSS compared to men (P < 0.05).ConclusionLV WSS showed a regular variation and had specific age- and sex-related patterns in different diastolic phases.

Left atrial strain in assessing heart failure with preserved ejection fraction in hypertensive patients

Aim. To compare the results of diagnosing heart failure with preserved ejection fraction (HFpEF) in patients with hypertension (HTN) according left atrial (LA) strain values with the results obtained using the H2FPEF score and diastolic stress testing (DST).Material and methods. The study included 293 patients with previously established HTN who were examined due to complaints of shortness of breath and/or palpitations (men, 97 (33,5%), mean age, 62,0 (55,0; 67,0) years). All patients underwent transthoracic echocardiography with the assessment of LA strain parameters and probability of HFpEF using the H2FPEF score. Eighty five patients with an intermediate probability of HFpEF underwent DST.Results. A low probability of HFpEF according to the H2FPEF score was registered in 35 (11,9%) patients, uncertain — in 206 (70,3%), high — in 52 (17,7%). DST was negative in 43 (50,6%) and positive in 42 (49,4%) patients with an intermediate probability of HFpEF. LA strain in the reservoir phase in patients with a low probability of HFpEF averaged (median and interquartile interval) 28,0 (23,6; 31,5)%, while in patients with an intermediate probability and negative DST — 24,0 (22,0; 26,8)%, with an intermediate probability and positive DST — 20,0 (18,0; 21,0)%, and with a high probability of HFpEF — 19,6 (16,9; 21,8)%. HFpEF was diagnosed in 94 patients, including 52 with a high probability on the H2FPEF score and 42 with an intermediate probability and positive DST. The diagnosis of HFpEF was ruled out in 78 patients, including 35 with a low probability on the H2FPEF score and 43 with an intermediate probability and negative DST. Further, 172 patients with confirmed or excluded HFpEF were randomly divided into two equal cohorts. In the training cohort, HFpEF was diagnosed in 44 (51,2%) patients, in the validation cohort — in 50 (58,1%). ROC analysis performed on the training cohort for the LA strain in reservoir phase showed AUC of 0,920 (95% confidence interval (CI), 0,842-0,968) and cut-off point of 21,5%. In the training cohort, the results of HFpEF diagnosis using the indicated criterion coincided with those using H2FPEF score and DST in 86,1% (95% CI, 77,2-91,8) of cases. The Cohen’s kappa was 0,721 (95% C,I 0,575-0,868). In the validation cohort, agreement was observed in 84,9% (95% CI 75,8-91,0) of cases with Cohen’s kappa of 0,702 (95% CI 0,553-0,851).Conclusion. In hypertensive patients, the diagnosis of HFpEF made on the basis of a decrease in the LA strain in reservoir phase to ≤21,5%, is in good agreement with the diagnosis made using the H2FPEF score and DST.

Abstract P1046: An Oxygen Gradient Microphysiological System To Model The Myocardial Infarct Border Zone

After a myocardial infarction, the border zone is characterized by an oxygen (O 2 ) gradient located at the interface between the injured, hypoxic cardiac tissue and adjacent normoxic, viable tissue. Yet, the impact of an O 2 gradient on cardiac function is not well understood because there is a lack of in vitro experimental platforms for generating such biomimetic O 2 landscapes. This unmet need has prevented systematic investigation into how hypoxic-normoxic intercellular communication affects cardiac function. In this study, a microphysiological system was engineered to generate and expose engineered cardiac tissues to a stable O 2 gradient as a “Border-Zone-on-a-Chip” model. Briefly, a microfluidic gas supply channel network was overlaid with a thin, gas-permeable polydimethylsiloxane membrane on which engineered cardiac tissue composed of neonatal rat ventricular myocytes was cultured. Constant perfusion of compressed gases through separate microfluidic channels and rapid diffusion of the gas conditions across the thin membrane produced an O 2 gradient. Functional and transcriptomic analysis revealed biological responses were uniquely regulated by an O 2 gradient when compared to engineered tissues exposed to global, homogeneous O 2 levels. In the gradient, there was a significant increase in the calcium transient time to peak (85%, p=0.0007) and tau time constant of decay (49%, p=0.006). There was a significant decrease in the longitudinal calcium wave propagation velocity (35%, p=0.03), diastolic stress (47%, p=0.01), and peak systolic stress (47%, p=0.01). Overall, the gradient exhibited hallmarks of arrhythmogenesis, hypocontractility, and activation of inflammation after 4 h of O 2 modulation. Importantly, these changes were distinct from those observed in tissues exposed to uniform normoxia or hypoxia, demonstrating distinct regulation of cardiac tissue phenotypes by an O 2 gradient. Studies are ongoing to elucidate a possible paracrine mechanism involved in the observed effects. By gaining functional and mechanistic insight into intercellular communication activated in O 2 gradients, microphysiological systems can direct future therapeutic strategies aimed at minimizing or preventing cardiac hypoxic injury.

Contractile Reserve in Heart Failure with Preserved Ejection Fraction.

Background: Diastolic stress echocardiography (SE) is useful for confirming the diagnosis of heart failure with preserved left ventricular ejection fraction (HFpEF) when it is uncertain. The aim of this study was to assess the value of new echocardiographic parameters during diastolic SE in patients with dyspnea and suspected HFpEF. Methods: Sixty-two patients with exertional dyspnea and inconclusive rest echocardiography for a diagnosis of HFpEF were enrolled. Exercise SE was performed in all patients. Contractile reserve (LVCR) was assessed by measuring: 1. changes in the left ventricular ejection fraction (LVEF) between rest and peak stress; 2. stress-to-rest ratio of force (force was defined as the ratio between systolic arterial pressure and left ventricular end-systolic volume); and 3. mechanical reserve, defined as the change in systolic strain (GLS) between rest and peak stress. Results: Diagnosis of HFpEF was performed by SE in 26 patients. Comparing patients with a diagnosis of HFpEF (group A) to patients with other causes of dyspnea (group B), we found a significant increase in the E/e’ ratio in group A at peak stress. LV GLS was significantly reduced in group A compared to group B at rest and stress (p value 0.01 at rest; p value 0.04 at stress). At peak stress, GLS did not significantly increase in group A, while it increased in group B (p value 0.04). LVEF increased significantly in both groups. Conclusion: Patients with HFpEF have impaired LVCR when assessed using GLS. Thus, the assessment of mechanical reserve could give additional diagnostic information during stress tests in patients with HFpEF.

Value of Diastolic Stress Echocardiography Combined with Speckle Tracking Imaging in Assessment of Patients with Exertional Dyspnea and Normal Resting Left Ventricular Functions

Value of Diastolic Stress Echocardiography Combined with Speckle Tracking Imaging in Assessment of Patients with Exertional Dyspnea and Normal Resting Left Ventricular Functions

Diastolic stress echocardiography and biomarkers in patients with preserved left ventricle ejection fraction and heart failure symptoms.

Diastolic dysfunction (DD) is a diagnostic challenge in clinical practice. Our study aimed to evaluate the value of diastolic stress echocardiography (DSE) and heart failure (HF) biomarkers in patients with preserved left ventricular ejection fraction (LVEF) and HF symptoms. All the consecutive patients with HF symptoms, preserved LVEF, and suspected DD were examined on transthoracic echocardiography (TTE) and DSE using the protocol according to the American Society of Echocardiography recommendations. Moreover, blood samples were taken 30 minutes before and after DSE for the following lab markers: N-terminal pro-B type natriuretic peptide (NT-proBNP), mid regional pro-atrial natriuretic peptide (MR-proANP), and serum soluble ST2 receptor (ST2). The study group included 80 patients (mean [standard deviation, SD] age, 69 (8.1) years; 25% males) with dyspnea (New York Heart Association classification IIa - 53; IIb - 17; III - 10) and risk factors: hypertension (96%), diabetes (41%), obesity (56%), and known coronary artery disease (10%). The rest transthoracic echocardiography (TTE) showed preserved systolic function (mean [SD], LVEF 61.1 [10.5]%) and normal or indeterminate diastolic function. DSE revealed a positive result for diastolic dysfunction in 17 patients (21%). The receiver operating characteristic (ROC) analysis showed that age (the area under the curve [AUC], 0.725; P < 0.01), left atrial volume indexed for body surface area [LAVI] rest (AUC, 0.722; P < 0.01), E/e' rest (AUC, 0.790; P < 0.01), and baseline NT-proBNP (AUC, 0.713; P < 0.01) predicted positive DSE. Other parameters, including body mass index, baseline E/A, DT, or e' were not predictive of DSE results. DSE revealed diastolic dysfunction in 21% of study patients and improved the diagnostic value of echocardiography. Rest NT-proBNP, but not MR-proANP and ST2, provided a diagnostic value for diastolic dysfunction.

MO747: Endotrophin Levels are Extremely Elevated in Dialysis Patients with Heart Failure with Preserved Ejection Fraction (HFPEF) and are Influenced by Background Treatment with Diuretics and ARBS/ACEI

Abstract BACKGROUND AND AIMS Endotrophin, a bioactive molecule derived from the cleavage of the collagen type VI pro-peptide, released during collagen maturation, has been associated with multiple pathogenic processes, including inflammation and fibrosis. PRO-C6, a biomarker reflecting circulating endotrophin levels, has been associated with an adverse prognosis in multiple disease settings, including chronic kidney disease and heart failure with preserved ejection fraction (HFpEF). Here, we assessed levels of PRO-C6 in a population of dialysis patients with and without heart failure, and we observed an association of PRO-C6 with imaging and soluble biomarkers of heart disease, presence of co-morbidities and medications. METHOD PRO-C6 was measured with the enzyme-linked immunosorbent assay developed by Nordic Bioscience (Denmark) in serum of 46 patients undergoing dialysis (mean age 70 years, 37% female) and with HFpEF (61%), HFmrEF (7%), HFrEF (2%) or no HF (30%) collected at the Clínica Universidad de Navarra (Spain). The samples were collected pre-dialysis. PRO-C6 was also measured in serum of 50 healthy individuals (mean age 61 years, 50% female) collected at the same site. Differences between groups were estimated with the Kruskal–Wallis test, correlations were estimated with Spearman’s rank correlation coefficient. RESULTS Levels of PRO-C6 were extremely elevated in the serum of dialysis patients compared with healthy individuals (81 ng/mL versus 6.3 ng/mL; P &amp;lt; 0.0001), and also compared with previously seen levels in HFpEF patients (patients with levels above 16 ng/mL were at increased risk of worse outcome in the TOPCAT cohort). Among the dialysis patients, patients with HFpEF had significantly increased PRO-C6 levels compared with patients with no HF (90.2 ng/mL versus 61.8 ng/mL; P = 0.03). Due to the low number of events, the numerical increase in PRO-C6 levels in patients that died, had myocardial infarction and pulmonary hypertension did not reach statistical significance. PRO-C6 showed modest direct correlations with age, NT-proBNP, hsTNT and collagen type I C-terminal telopeptide (CITP), and a modest inverse correlation with eGFR. When looking at echo parameters, PRO-C6 was modestly directly correlated with left ventricular posterior wall thickness and relative wall thickness and modestly inversely correlated with left ventricular end diastolic volume. Interestingly, patients treated with ARB/ACEi and diuretics presented significantly lower levels of PRO-C6 compared with those that were not receiving these drugs (64.4 ng/mL versus 90.2 ng/mL; P = 0.01 and 59.0 ng/mL versus 87.1 ng/mL; P = 0.008, respectively). Patients treated with antiplatelets on the contrary had higher levels of PRO-C6 (88.9 ng/mL versus 67.7 ng/mL; P = 0.04). CONCLUSION Even in a population of kidney failure patients, presenting very high levels of circulating endotrophin, the presence of HFpEF was associated with further increased levels of endotrophin. Moreover, endotrophin levels were associated with echo parameters and biomarkers reflecting diastolic disfunction and left ventricular stress and damage. We have shown here for the first time that patients treated with ARB/ACEi and diuretics present lower levels of circulating endotrophin. PRO-C6 measuring endotrophin confirms being a biomarker of interest in HFpEF patients, even in the presence of kidney failure.

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

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

Exercise Stress Echocardiography in the Diagnostic Evaluation of Heart Failure with Preserved Ejection Fraction

More than half of patients with heart failure have a preserved ejection fraction (HFpEF). The prevalence of HFpEF has been increasing worldwide and is expected to increase further, making it an important health-care problem. The diagnosis of HFpEF is straightforward in the presence of obvious objective signs of congestion; however, it is challenging in patients presenting with a low degree of congestion because abnormal elevation in intracardiac pressures may occur only during physiological stress conditions, such as during exercise. On the basis of this hemodynamic background, current consensus guidelines have emphasized the importance of exercise stress testing to reveal abnormalities during exercise, and exercise stress echocardiography (i.e., diastolic stress echocardiography) may be used as an initial diagnostic approach to HFpEF owing to its noninvasive nature and wide availability. However, evidence supporting the use of this method remains limited and many knowledge gaps exist with respect to diastolic stress echocardiography. This review summarizes the current understanding of the use of diastolic stress echocardiography in the diagnostic evaluation of HFpEF and discusses its strengths and limitations to encourage future studies on this subject.

Novel method of diastolic stress echocardiography during bottle-feeding for infants with congenital heart disease

Abstract Funding Acknowledgements Type of funding sources: None. Background Recent studies have demonstrated the utility of diastolic stress echocardiography in evaluating diastolic dysfunction during exercise in adults. However, there have been no such reports in infants. This study determined whether measuring cardiac function using echocardiography during bottle feeding is a valid method of stress testing in infants with congenital heart disease. Methods The study population comprised 25 infants with congenital heart disease (Table 1). Echocardiographic measurements of the infants were taken during and after bottle feeding (Figure 1A). Active feeding (AF) was defined as the start of feeding during which the heart rate started increasing. End of feeding (EF) was defined as the time of completion of feeding during which the heart rate slowed down. The 25 infants were divided into two groups according to brain natriuretic peptide levels: less than 50 pg/ml (low group) and more than 50 pg/ml (high group). Cardiac function was compared between the groups using 2D speckle tracking analysis, and intraventricular pressure differences (IVPD) via color M-mode Doppler (Figures 1B and 1C) and 2D echocardiography. We compared the fractional change (FC%), defined as (AF and EF measurements)/EF measurements, between the two groups. Results Heart rate increased AF comparing with EF, significantly in both groups, the low group from 162 to 139 bpm; the high group from 152 to 140 bpm. The FC_IVPD was higher in the low group than in the high group (Figure.2). There were negative correlations between brain natriuretic peptide levels and the FC_IVPD (Figure 3). There were 4 cases were performed the intra-cardiac repair (ICR). In 2 cases, VSD and right ventricular outflow tract obstruction (RVOTO) velocity were increased during feeding. Indication of ICR, VSD case was aortic regurgitation with aortic cusp prolapse, TOF case was RVOTO. In VSD peak velocity in 2 cases did not increase during feeding (Table2). Indication of ICR, two VSD cases were moderate left to right shunt, or pulmonary hypertension. Conclusions Our findings indicate that stress echocardiography during bottle-feeding might be a substitute for diastolic stress echocardiography in infants. The VSD or RVOT peak velocity, and FC% in IVP D and IVPG are sensitive markers for cardiac function in infants with congenital heart disease. Abstract Table1 Abstract Figure.

Association between diastolic stress test and H2FPEF score.

Objective:Heart failure with preserved ejection fraction is a highly prevalent disease; some advances for improving the ­diagnosis are the development of the H2FPEF score and the diastolic stress test for the evaluation of diastolic function. The objective is to describe the clinical and echocardiographic characteristics of patients referred for stress tests, and the association between the H2FPEF score and the results of the diastolic test.Methods:This is an analytical, observational, retrospective study. An exercise stress test was performed. The Chi-square test was used to establish an association between H2FpEF score and diastolic stress test results. Patients over the age of 18, in sinus rhythm, with the left ventricular ejection fraction > 54%, with no more than mild diastolic dysfunction on the baseline echocardiogram were included in the study.Results:A total of 99 patients met the eligibility criteria. About 49.5% were women, median age was 62.2 years. The H2FPEF score was low in 27.2%, intermediate 71.7%, and 1% in the high range. There was a high prevalence of hypertension 58.6%, diabetes 12.1%, and coronary disease 20.2%. The stress test was positive for diastolic dysfunction in 36.4% of the patients. A statistically significant association was found between the H2FPEF score and the diastolic stress test (p = 0.02).Conclusions:Although clinical scores such as H2FPEF help identify patients, a high percentage of patients are classified in the intermediate range. The diastolic stress test can help to make the diagnosis of diastolic function in this group of patients.

A Targeted Treatment Opportunity for HFpEF: Taking Advantage of Diastolic Tone.

A Targeted Treatment Opportunity for HFpEF: Taking Advantage of Diastolic Tone.

Comprehensive diastolic exercise stress echocardiography in heart failure with preserved ejection fraction

Abstract Background In heart failure with preserved ejection fraction (HFpEF), diastolic exercise stress echocardiography (ESE) is currently recommended with E/e' and systolic pulmonary artery pressure (SPAP) from tricuspid regurgitant jet velocity (TRV). Purpose To evaluate conventional and advanced ESE parameters in patients with HFpEF. Methods We prospectively screened 124 patients with suspected HFpEF (dyspnea, resting EF &amp;gt;50%, increased natriuretic peptide levels) and HFA-PEFF score ≥1. Of these 124, 10 patients were excluded for history of coronary artery disease, 3 for severe mitral regurgitation (MR), 12 for inducible ischemia. The final study population consisted of 99 patients (mean age 63±7 yrs, 57 females). All underwent ESE, with semi-supine bike (n=35), upright bike (n=20) or treadmill (n=44 patients) in 11 accredited labs from 9 countries (Argentina, Brazil, Bulgaria, Hungary, Italy, Lithuania, Mexico, Russia and Spain). In addition to E/e' average (abnormal stress response ≥15 units) and TRV (abnormal stress response &amp;gt;3.4 m/s), we measured 8 additional criteria: B-lines (4-site simplified scan, abnormal stress value ≥2); cardiac index (CI) reserve (increase from rest to stress, abnormal &amp;lt;1.63 l/min/m2), ejection fraction (EF, abnormal increase &amp;lt;5%), global longitudinal strain (GLS, abnormal increase &amp;lt;2%), end-diastolic volume (EDV, abnormal stress &amp;lt; rest); heart rate reserve (HRR, abnormal &amp;lt;1.80); left atrial volume index, (LAVI, abnormal increase &amp;gt;6.8 ml/m2); MR (abnormal, stress value more than mild). Results Technical success rate during stress ranged from 100% for B-lines to 75% for GLS: see Table. At individual criteria analysis, positivity rate in interpretable studies ranged from 67% of HRR to 10% of peak MR: see table. At individual patient analysis, an abnormal response in 1 ESE criterion occurred in 4 pts (4%), of 2 to 4 criteria in 71 pts (72%) and of ≥5 criteria in 24 (24%). Conclusion In suspected HFpEF, ESE is helpful in the screening phase to identify extra-diastolic causes of dyspnea such as myocardial ischemia or severe MR. In the diagnostic phase, a comprehensive ESE captures the functional heterogeneity of HFpEF, with variable association of multiple phenotypes, the most frequent represented by reduced chronotropic, cardiac or contractile reserve and pulmonary congestion. Funding Acknowledgement Type of funding sources: None.

Differences in left ventricular twisting and different strains in patients with heart failure with preserved ejection fraction versus patients with arterial hypertension

Abstract Patients with advanced arterial hypertension (HPT) without heart failure often have left ventricular (LV) changes similar to hypertensive patients with heart failure with preserved ejection fraction (HFpEF). We assumed that cardiac mechanics may be different in both groups. Methods We study 58 patients (23 female) with HPT and with left ventricular concentric hypertrophy (LVH) as well as negative diastolic stress test and 52 HPT patients (29 female) with HFpEF NYHA II-III 72±5 years. All patients where in sinus rhythm. HPT and HFpEF patients has comparable degree of LV mass index (LVMI 85.3±8.6 g/m2 vs 86.2±8.9 g/m2, P=NS). Incidence of diabetes mellitus, chronic kidney disease or chronic obstructive lung disease was comparable between groups. 43 sex and age matched healthy subjects served as control (C). Comprehensive 2D/3D echocardiography (EchoCG) with offline measurements of longitudinal (LS), circumferential (CS) and radial strain (RS) global values of entire walls and 3 myocardial layers, LV twist (LVT)was performed before and after symptom limited or heart rate of 120 bpm limited diastolic stress test. Results HPT and HFpEF patients had significantly lower absolute values LS, CS, AS, as well as lower values of RS, and LVT compared with controls at rest and after stress test. The values of LS, RS and LVT did not significantly differ at rest in HPT patients and HFpEF patients, but HFpEF patients had lower values of global CS (GCS) due to reduction only in endocardial layer CS (ECS) (LS: 16.4±5.2% vs 16,8±5.9, p=0.07; ECS: 10.9±2,3% vs 17.3±4.1%, p&amp;lt;0.01; GCS: 12.8±3.5% vs 15.1±2.1%, p&amp;lt;0.03; RS: 29.7±10.2% vs 31.1±12.4%, p=0.06; LVT: 2.3±1.4deg vs 2.6±1.7deg, p=0.06). After diastolic stress test patients with HFpEF had significantly lower values of LVT and GCS compared with HPT patients (LVT: 1.8±0.9deg vs 3.4±1.8deg, p&amp;lt;0.001; GCS: 10.4±2.7% vs 17.1±3.4%, p&amp;lt;0.01). We also found greater relative increase (RI) in endocardial LS and LVT in patients with HPT after stress test compared with HFpEF patients, RI of other parameters did not differ between these two groups (RI ELS: 16±2.1% vs 10.5±1,7%, p&amp;lt;0.03; RI LVT 33.3±6,4% vs −21.7±4.1%, p&amp;lt;0.0001). ECS had the diagnostic value to predict HFpEF (area under curve 0.874), RI LVT was the best predictor of HFpEF symptoms (area under curve 0.912) with cut off value 22.3%. Conclusion ECS is reduced in HFpEF patients compared with HPT patients with the same degree of structural abnormalities on conventional EchoCG and is a predictor of HFpEF. HPT patients have more relative improvement in ELS during stress test compared with HFpEF patients. RI LVT was the best predictor of HFpEF symptoms. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): City Hall resources

Right ventricular myocardial oxygen tension is reduced in monocrotaline-induced pulmonary hypertension in the rat and restored by myo-inositol trispyrophosphate

Pulmonary hypertension (PH) initially results in compensatory right ventricular (RV) hypertrophy, but eventually in RV failure. This transition is poorly understood, but may be triggered by hypoxia. Measurements of RV oxygen tension (pO2) in PH are lacking. We hypothesized that RV hypoxia occurs in monocrotaline-induced PH in rats and that myo-inositol trispyrophosphate (ITPP), facilitating oxygen dissociation from hemoglobin, can relieve it. Rats received monocrotaline (PH) or saline (control) and 24 days later echocardiograms, pressure–volume loops were obtained and myocardial pO2 was measured using a fluorescent probe. In PH mean pulmonary artery pressure more than doubled (35 ± 5 vs. 15 ± 2 in control), RV was hypertrophied, though its contractility was augmented. RV and LV pO2 was 32 ± 5 and 15 ± 8 mmHg, respectively, in control rats. In PH RV pO2 was reduced to 18 ± 9 mmHg, while LV pO2 was unchanged. RV pO2 correlated with RV diastolic wall stress (negatively) and LV systolic pressure (positively). Acute ITPP administration did not affect RV or LV pO2 in control animals, but increased RV pO2 to 26 ± 5 mmHg without affecting LV pO2 in PH. RV oxygen balance is impaired in PH and as such can be an important target for PH therapy. ITPP may be one of such potential therapies.

The myosin activator omecamtiv mecarbil improves wall stress in a rat model of chronic aortic regurgitation.

In patients with chronic aortic regurgitation (AR), excessive preload and afterload increase left ventricle wall stress, leading to left ventricular systolic dysfunction. Thus, the objective of the present study was to evaluate the effects of the myosin activator omecamtiv mecarbil (OM) on left ventricle wall stress in an experimental rat model of severe chronic AR. Forty adult male Wistar rats were randomized into two experimental groups: induction of AR (acute phase) by retrograde puncture (n = 34) or a sham intervention (n = 6). Rats that survived the acute phase (n = 18) were randomized into an OM group (n = 8) or a placebo group (n = 10). Equal volumes of OM (1.2 mg/kg/h) or placebo (0.9% NaCl) were continuously infused into the femoral vein over 30 min. OM significantly decreased end‐systolic and end‐diastolic and maximum wall stress in this experimental rat model of chronic severe AR (p < 0.001) and increased systolic performance assessed by fractional shortening and left ventricle end‐systolic diameter; both p < 0.05). These effects were correlated with decreased indices of global cardiac function (cardiac output and stroke volume; p < 0.05) but were not inferior to baseline pump indices. Infusion with placebo did not affect global cardiac function but decreased end‐systolic wall stress (p < 0.05) and increased systolic performance (all p < 0.001). In the sham‐operated (control) group, OM decreased diastolic wall stress (p < 0.05). Based on these results, OM had a favorable effect on left ventricle wall stress in an experimental rat model of severe chronic AR.

Quantitative magnetic resonance angiography to assess post embolization hemodynamics following pipeline embolization.

Delayed intraparenchymal hemorrhage is a known complication of the Pipeline Embolization device (PED); however, its etiology is unclear and some have suggested it is a flow related phenomenon. Quantitative magnetic resonance angiography (QMRA) serves as a powerful tool to collect and analyze hemodynamic data. We report a detailed characterization of short-term hemodynamics after PED placement. Patients who underwent PED placement for a distal internal carotid artery (ICA) aneurysm between 2017 to 2019 with post embolization QMRA were reviewed. Aneurysm characteristics, flow volume rate (ml/min), mean, systolic, and diastolic flow velocities (cm/s), vessel diameter (mm), pulsatility index, Lindegaard ratio, and wall shear stress (WSS) were collected. A total of 67 patients were included. Post-procedure patients were found to have a significantly lower ICA flow on the side with flow diversion when compared to the side without flow diversion (218 vs. 236.3; P < 0.05). Average ICA flow after flow diversion for aneurysms >2 cm was significantly lower when compared to the untreated side (187.7 vs. 240.4; P < 0.05). There was no difference in MCA or ACA flow or velocity. WSS was significantly lower in the treated ICA (8.2 vs. 9.0; P < 0.05). Lindegaard ratio was not different in the treated vs. contralateral untreated sides. PED placement for distal ICA aneurysms results in lower flow, mean velocity, and WSS when compared to the contralateral untreated ICA. This is not demonstrated distal to the Pipeline device in the ACA or MCA territories. Ultimately these findings suggest hemodynamic changes are not a cause of PED complications.

EACVI survey on the evaluation of left ventricular diastolic function.

The aim of this study is to analyse how current recommendations on left ventricular (LV) diastolic function assessment have been adopted. Identifying potential discrepancies between recommendations and everyday clinical practice would enable us to better understand and address the remaining challenges in this controversial and complex field. A total of 93 centres, mainly from tertiary care settings, responded to the survey. More than three-quarters (77%) of centres follow the 2016 ASE/EACVI recommendations for LV diastolic function evaluation in patients with preserved ejection fraction based upon e', E/e', tricuspid regurgitation velocity, and left atrial (LA) volume. These recommendations were generally preferred to the previous 2009 version. Many centres also consider strain assessments in the LV (48%) and left atrium (53%) as well as diastolic stress echocardiography (33%) to be useful as additional assessments of LV diastolic function. Echocardiographic assessments of LV diastolic function were used frequently to guide therapy in 72% of centres. There is widespread adoption of current recommendation on the evaluation of LV diastolic function and these are frequently used to guide patient management. Many centres now also consider LV and LA strain assessments useful in the clinical assessment of diastolic function. These may be considered in future recommendations.