Functional Assessment Research Articles

The correlation between angio-IMR and thermodilution-based IMR in patients with ischemia and non obstructive coronary arteries

Abstract Background The diagnostic dilemma of angina with no obstructive coronary lesions (INOCA) poses remarkable challenges in clinical practice, and presents as a significant disease burden affecting up to 4 million people annually. Additionally, standard diagnostic tests such as angiography, do not reveal microvascular dysfunction despite clinical symptoms being present. Since the current Gold Standard of functional assessment is based on guidewire dependent measurements (i.e. CFR, IMR). As an invasive method, it is associated with an increased risk of adverse events such as arterial damage. Therefore new modalities are being introduced to improve patient safety, specifically, an angio-IMR (QMR, calculated based on angiography), shows a substantial promise as a potential diagnostic tool for INOCA patients. Purpose The aim of this study is to assess correlation between angio-IMR and thermodilution-based invasively measured IMR in INOCA patients. Methods In a group of INOCA patients who had undergone coronary angiography with concomitant thermodilution-based assessment of index of microcirculatory resistance (IMR) an additional angio-based IMR calculation was performed. The INOCA group consisted of 92 patients ranging in age from 49 to 80 years old, with a median age of 66 years. The majority of the patients were female (59.3%), predominantly with arterial hypertension (87%) and dyslipidemia (100%). Diabetes was present in 27% of cases. Angio-IMR (QMR) was determined by a qualitative angiography software using information about aortic pressures registered during angiography. Coronary microcirculatory dysfunction (CMD) was diagnosed according to current guidelines when IMR ≥ 25 or CFR < 2.0 were present. Results Increased IMR values were detected in 26% of patients. Median calculated value of angio-IMR value was 29 [IQR: 22,46], whereas the invasively measured IMR median value was 17 [IQR: 13,26]. A significant correlation between angio-IMR and invasive-IMR values was observed, Spearman Rho 0.29, p<0.001. Detailed scatterplot with histograms is presented in the figure. Conclusions Noninvasive methods, such as the Angio-IMR, represent a shift towards reducing the need for additional invasive procedures while still providing valuable diagnostic insights. Angio-IMR is significantly correlated with invasively measured IMR. When evaluated along with the clinical presentation, noninvasive approaches may therefore help mitigate certain risks and healthcare costs associated with invasive techniques.Figure.Correlation angio-IMR vs MR

Association between platelet-to-high-density lipoprotein cholesterol ratio and cognitive function in older americans: insights from a cross-sectional study

The main aim of this study was to explore the correlation between the platelet/high-density lipoprotein cholesterol ratio (PHR) and cognitive function in elderly individuals from the United States. This investigation leveraged data encompassing 2299 participants, all aged 60 years and above, from the National Health and Nutrition Examination Survey conducted from 2011 to 2014. Inclusion criteria were based on the availability of complete datasets for PHR and cognitive function assessments. The analytical approach incorporated multivariate logistic regression to discern the association between PHR and cognitive function. Additionally, the study employed restricted cubic splines (RCS) to explore potential non-linear relationships and subgroup analyses to identify variations in the observed associations across different demographic and clinical subgroups. In the fully adjusted model, an increment of 10 units in PHR was associated with a decline of 0.014 in cognitive scores (β=-0.014, 95% CI: -0.025, -0.002; P < 0.05). Compared to the lowest quartile, participants in the highest quartile exhibited a 38.4% increased prevalence of cognitive impairment per one-unit increase in PHR (OR = 1.384, 95% CI: 1.012, 1.893; P < 0.05). Subgroup analysis revealed consistent results regarding the relationship between PHR and cognitive impairment across all subgroups. A non-linear relationship between PHR and cognitive impairment was observed using RCS, indicating that an increase in PHR above 111.49 significantly elevated the incidence of cognitive impairment (P < 0.05). Our study demonstrates that a higher PHR is associated with a greater risk of cognitive decline in an older U.S. population, and although further validation is needed, this warrants consideration in clinical assessments and interventions.

Right ventricular myocardial work: a step forward for the assessment of right ventricular to pulmonary artery coupling

Abstract Background Right ventricular myocardial work (RVMW) is a novel method for non-invasive assessment of right ventricular (RV) function. By integrating RV global longitudinal strain as systolic function parameter, pulmonary systolic and diastolic pressures as afterload indices, and pulmonary and tricuspid valves timings, RVMW could provide a more comprehensive evaluation of RV function. Purpose The aim of this study was to assess patterns of RVMW indices in patients with preserved and impaired RV to pulmonary artery (PA) coupling (RVAC), as assessed by RV free wall longitudinal strain/pulmonary artery systolic pressure (RVFWLS/PASP) ratio. Methods We studied by echocardiography 158 consecutive patients with stable HF and left ventricular (LV) systolic dysfunction (LV ejection fraction &amp;lt; 50%). RVAC was assessed by RVFWLS/PASP and patients were grouped according to the median value. Four parameters of RVMW were obtained: RV global work index (RVGWI), RV global constructive work (RVGCW), RV global wasted work (RVGWW) and RV global work efficiency (RVGWE). Results According to RVFWLS/PASP ratio, patients were divided into two groups: A) preserved RVAC (RVFWLS/PASP ratio ≥ 0.51; N=84) and B) impaired RVAC (RVFWLS/PASP ratio &amp;lt; 0.51; N= 74). Both RVGWI (371±156 vs 384±207 mmHg%, P=NS) and RVGCW (449±171 vs 516±249 mmHg%, P=NS) did not significantly differ between the two groups (figure 1). However, group B (impaired RVAC) showed significantly greater RV wasted work (94±69 vs 44±30 mmHg%, P=0.0001) and significantly lower RV work efficiency (80±13 vs 88±8 %, P=0.0001) compared to group A (preserved RVAC, figure 2). Conclusions RVMW provided new insight in the RV function assessment, highlighting lower efficiency due to higher wasted work in RV to PA uncoupled patients.Figure 1Figure 2

Preliminary findings of the TB-HEART Study: prevalence of cardiac pathology among newly diagnosed patients with tuberculosis with and without HIV in Zambia

Abstract Background Cardiovascular diseases (CVD) burden is rapidly increasing in sub-Saharan Africa (SSA) where tuberculosis and HIV prevalence remain high.(1-3) Recent data suggest pulmonary tuberculosis (PTB) is associated with increased CVD morbidity.(4) However, the mechanisms of cardiac injury remain poorly understood. Purpose The TB-HEART study is a cross-sectional and natural history study consecutively recruiting participants with newly-diagnosed PTB, living with and without HIV in Zambia. The primary outcome is the burden of cardiac pathology in PTB patients with and without HIV. Methods Participants with bacteriologically-proven PTB, consecutively recruited from an outpatient settings in Zambia, undergo detailed clinical and functional assessments including point-of-care and standard two-dimensional (2D) echocardiography. Participants are reviewed at completion of TB treatment when all assessments are repeated. The target sample size is 250 participants with PTB, with and without HIV, matched 2: 1 to participants without PTB, stratified by HIV. Results Since 1 November 2023, we have recruited 73 participants with a mean age of 35.3±10.9 years of whom 51/73 (69.9%) are male and 19/73 (23.5%) are living with HIV. Baseline characteristics including cardiovascular risk factors, TB symptoms, anthropometry and clinical and functional observations at presentation, stratified by HIV status, are summarised in Table 1. We detected significant cardiac pathology (defined as left ventricular ejection fraction (LVEF) &amp;lt;51% and/or pericardial effusion &amp;gt;2cm in depth) in 8/65 (12.3%) participants for whom 2D-echocardiography had been completed. Median LVEF was 61.2% (IQR 57.7-67.8). LVEF was normal in 59/65 (91%); mildly abnormal in 5/65 (7.7%); and moderately abnormal in 1/65 (1.5%) participants, respectively. Pericardial effusion &amp;gt;0.5cm was detected in 16/65 (24.6% ) participants and maximum effusion depth was &amp;gt;2cm in 2/16 (3.1%), 1-2cm in 12/16 (75%) and &amp;lt;1cm in 2/16 (12.5%). 2D-echocardiography findings, stratified by HIV-status, are described in Table 2 alongside two echocardiography stills of typical pericardial effusion findings in one participant. Conclusions Our preliminary results demonstrate a higher than expected prevalence of cardiac pathology among participants with PTB with and without HIV, which ranges from 1-7% in autopsy studies and case series.(5-7) The most common cardiac pathology was pericardial effusion. Further analyses will include cardiac biomarkers; repeat clinical and echocardiographic assessments at TB treatment completion; and comparator data, to determine associations between prevalent cardiac pathology and PTB controlling for HIV and TB status, respectively. This may have important implications for clinical practice to prevent complications such as constrictive pericarditis; and policy design to better integrate TB and HIV patient services with preventative care to reduce future CVD risk.Table 1 - Baseline characteristicsFigure 1 and Table 2

Comparative analysis of post-PCI fractional flow reserve and quantitative flow ratio in predicting long-term Target Vessel Failure and hard endpoints

Abstract Background The role of functional assessment after angiographically acceptable post-PCI result is debatable. Purpose We sought to investigate the correlation between Fractional Flow Reserve measured directly after drug eluting stent (DES) implantation (post-PCI FFR) and post-PCI Quantitative Flow Ratio (post-PCI QFR), clarify their relationship with clinical parameters, and long-term target vessel failure (TVF: cardiac death (CD), non-fatal target vessel myocardial infarction (MI) and target vessel revascularisation (TVR)), and a composite of CD and MI (CD/MI). Method Coronary arteries that underwent post-PCI FFR measurement at our centre between 2012 and January 2021 were consecutively included in this registry. Post-PCI QFR was calculated blinded to the post-PCI FFR value. We analysed the influence of LAD vs. (non-LAD) location, gender, age, hypertension, diabetes mellitus, hyperlipidemia, indication (acute (ACS) vs. chronic coronary syndrome), stent diameter, in-stent restenosis (ISR) vs. de novo lesion category, estimated glomerular filtration rate, proximal vs. distal lesions, severe aortic stenosis, atrial fibrillation during the procedure (AF), and prior myocardial infarction in the supply area (prior MI) on post-PCI FFR and QFR. Optimal cut-off was determined by ROC curves. Results A total of 400 coronary arteries were analysed. LAD location (p&amp;lt;0.001), male gender (p=0.0029) and smaller stent diameter (p=0.0073) proved to be predictors of a lower post-PCI FFR. LAD location (p=0.001), ISR (p=0.02), distal location (p=0.0019), AF (p=0.042) and prior MI (p=0.029) were predictors of a lower post-PCI QFR. There was a systematic bias in post-PCI QFR compared to post-PCI FFR (bias 0.0614, 95% CI, 0.053 - 0.069). During a median follow-up of 45 months, 31 CD, 20 MI and 35 TVR occurred. Follow-up was complete in 100%. There was a significant inverse correlation between post-PCI FFR and TVF (p&amp;lt;0.001) as well as between post-PCI QFR and TVF (p=0.045). In-stent restenosis (p=0.014) and prior MI (p=0.002) were also predictors of higher TVF rate. The predictors of CD/MI were lower post-PCI FFR (p&amp;lt;0.001), smaller stent diameter (p=0.03), higher age (p=0.031) and ACS indication (p=0.048), whereas post-PCI QFR was not. The best post-PCI FFR cut-off to predict TVF was 0.87 (p&amp;lt;0.0001). There was no single optimal post-PCI QFR cut-off to predict TVF. Conclusion Post-PCI QFR shows a systematic bias compared to post-PCI FFR. Post-PCI FFR is a significant predictor of TVF as well as CD/MI, whereas post-PCI QFR predicts TVF. No significant correlation between post-PCI QFR and CD/MI could be demonstrated. Our findings underscore the importance of considering multiple clinical parameters in predicting long-term outcomes. The best post-PCI FFR cut-off to predict TVF was 0.87. However, there was no single, universally applicable post-PCI QFR threshold to predict TVF.

Coronary flow characteristics in cases with discordance between coronary flow reserve and the index of microvascular resistance in the assessment of coronary microvascular dysfunction

Abstract Background/Introduction Coronary flow reserve (CFR) and the index of microvascular resistance (IMR) are commonly used for the diagnosis of coronary microvascular dysfunction, but the two indices can reveal discordance. Purpose The aim of this study was to investigate the mechanisms of the discordance between CFR and IMR. Methods Haemodynamic data from patients who underwent invasive coronary functional assessment using a guidewire equipped with pressure and temperature sensors was analysed. We performed vessel-based analysis, and classified vessels with reference to the criteria of IMR ≥25 and CFR &amp;lt;2.0 as pathological into four groups: normal IMR/normal CFR (Group 1: G1), abnormal IMR/normal CFR (Group 2: G2), normal IMR/abnormal CFR (Group 3: G3), and abnormal IMR/abnormal CFR (Group 4: G4). Results Of 249 vessels form 176 patients, 82 (33%) were classified into G1, 28 (11%) into G2, 94 (38%) into G3, and 45 (18%) into G4. Median and interquartile ranges of IMR of the four groups were 14.3 [10.7–18.9], 34.2 [29.8–45.1], 16.9 [12.7–19.7], and 30.7 [28.4–43.5] (P &amp;lt;0.001), respectively, and those of CFR were 3.21 [2.48–4.29], 2.73 [2.34–3.03], 1.27 [1.06–1.55], and 1.28 [1.07–1.67] (P &amp;lt;0.001), respectively (Figure). In G2, hyperemic flow velocity was as low as G4 (1.97 [1.47–2.29] vs. 1.95 [1.41–2.50] sec-1, P=1.00), and the baseline flow velocity was lower than G4 (0.71 [0.49–0.85] vs. 1.44 [0.93–1.96] sec-1, P &amp;lt;0.001), leading to apparently normal CFR despite the diminished hyperemic flow. In G3, the hyperemic (3.60 [2.77–4.73] vs. 1.95 [1.41–2.50] sec-1, P &amp;lt;0.001) and the baseline flow velocity (2.85 [2.19–3.92] vs. 1.44 [0.93–1.96] sec-1, P &amp;lt;0.001) were higher than G4, leading to apparently decreased CFR despite the maintained hyperemic flow. Conclusion(s) The discordance between IMR and CFR can be explained by decreased coronary flow in abnormal IMR/normal CFR, and by increased baseline coronary flow in normal IMR/abnormal CFR.

Prediction of cancer therapy related cardiac dysfunction by using a machine learning approach with cardiac magnetic resonance images

Abstract Background There is inconsistent data on the value of baseline and early cardiac function assessment on identifying patients at risk of cancer therapy related cardiac dysfunction (CTRCD). Whether machine learning (ML) approaches applied to cardiac MRI (CMR) images may help risk stratify patients is unclear. Purpose In women with HER2+ breast cancer receiving sequential anthracyclines and trastuzumab we sought to (i) assess if a ML approach applied to pre-cancer therapy and early post anthracycline CMR short axis (SAX) cines can help identify patients at risk for future CTRCD and (ii) whether this approach is superior to using clinical and manual quantitative CMR data. Methods Women with HER2+ breast cancer from the EMBRACE-MRI study underwent 5 CMR studies (pre-cancer therapy, post anthracyclines, 3, 6 and 12 months during trastuzumab). CTRCD was defined using the CREC criteria by end of treatment. Three models were created: 1) clinical data (demographics, cardiovascular risk factors and medications); 2) clinical and manual quantitative CMR data (right and left ventricular volumes and LVEF); and 3) ML model based on SAX cine CMR images only. We focused on the pre-cancer therapy CMR and 1st visit post-anthracycline CMR. All images underwent standardised formatting. A 3D convolutional neural networks model architecture was used. The model consisted of multiple convolutional layers followed by max pooling and global average pooling layers. The output of the convolutional layers were then fed into a dense layer of 128 nodes incorporating an L2 activity regularizer and a subsequent dropout layer. To train and tune the model, the process was iterated 50 times. In each iteration, the patient participant dataset was shuffled, and a random 80% of patients were selected for training and tuning. The tuned model was then applied to the remaining 20% of patients in each iteration, and this entire cycle of shuffling, training, and testing was repeated 50 times with replacement. Area Under the Curve (AUC), accuracy, sensitivity, and specificity were calculated on the test set and averaged across folds to determine each model’s performance. Results 135 women were included (mean age 51.1±9.2 years) mean doxorubicin equivalent was dose 204.9±12.5mg/m2. Cardiovascular risk factors were prevalent: 33 (24%) had a smoking history; 21 (15%) had hypertension. 37 (27%) developed CTRCD. The ML model using baseline CMR cine data only had a higher AUC (0.84 95% CI [0.83-0.86]) for the detection of CTRCD compared to clinical data (0.62 95% CI [0.59-0.65]) and clinical and CMR data (0.62 95% CI [0.60-0.65]). This further improved with the addition of post-anthracycline CMR data (Table 1). Conclusion A ML model examining early cardiac MRI data with short axis cine CMR images performed better than those using clinical or manual quantitative CMR data for the prediction of CTRCD. Further studies including external validation are needed.Table 1 Mean and 95% CIs

Rehabilitation delivery models to foster healthy ageing - a scoping review

Abstract Background Rehabilitation is crucial for healthy ageing among older adults, who face heightened risks of non-communicable diseases, infections, injuries, and mental health issues. Yet, understanding tailored rehabilitation for this demographic remains limited. To fill this gap, we conducted a scoping review to identify rehabilitation delivery models targeting older adults’ functioning and healthy ageing. Methods We systematically searched Medline and Embase (January 2015 to May 2022) for English-language studies on rehabilitation approaches for older adults. Three authors independently screened records for eligibility and synthesized findings through quantitative and qualitative analysis. Results Among 6,933 records, we assessed 585 articles, identifying 283 studies with 69,257 participants. Six main rehabilitation delivery models emerged, with outpatient (24%) and telerehabilitation (22%) being predominant. Multidisciplinary teams (31.5%) often followed integrated care principles (30.4%). However, most studies adopted a disease-centric approach (59.0%), neglecting prevalent issues like pain, sensory impairments, incontinence, and sexual dysfunctions. Therapeutic exercises (54.1%) and self-management education (40.1%) were common interventions. Conclusions Our scoping review outlines diverse rehabilitation delivery models for older adults, highlighting gaps in addressing prevalent issues and emphasizing evidence-based strategies to promote healthy ageing. It underscores the need for systematic functional assessment and expansion of rehabilitation programs to cover prevalent health concerns. While limitations include reliance on published research and not assessing model effectiveness, this review lays groundwork for future research and innovation in rehabilitation and healthy ageing. Key messages • The scoping review identifies six rehabilitation delivery models for older adults. • The scoping review advocates for evidence-based strategies for enhancing healthy ageing through rehabilitation.

Prognostic role of post-percutaneous coronary intervention quantitative flow ratio

Abstract Background/Introduction Accumulated evidence supports the prognostic value of post–percutaneous coronary intervention (PCI) physiological measurement. Quantitative Flow Ratio (QFR) is a well-studied angiography-based method for functional assessment. Purpose To investigate the possible prognostic implications of post-PCI QFR in patients undergoing revascularization. Methods We performed offline QFR analysis in all-comers undergoing PCI in a single center. A cut-off value of 0.8 was used to classify patients in high post-PCI QFR group (&amp;gt;0.8) and low post-PCI QFR group (≤0.8). Patients with at least one vessel with post-PCI QFR ≤0.8 were classified in the low post-PCI QFR group. Primary endpoint was the composite outcome of death, myocardial infraction, ischemia-driven revascularization, and heart failure-related hospitalization. Results We included 297 patients in the study. Mean age was 64 (±11) years and 81% of patients were male. Number of patients presented with chronic coronary syndrome was comparable to that of patients presented with acute coronary syndrome (52.9 vs 47.1 %, respectively). Patients in the low post-PCI QFR group had more often diabetes mellitus, lower left ventricular ejection fraction (LVEF) and higher SYNTAX score compared to patients in the high post-PCI QFR group. Median follow-up period was 29 (26-34) months. After adjusting for covariates, low post-PCI QFR was independently associated with higher rate of the composite outcome (HR: 2.22 95% CI 1.01-4.88, p=0.047). Conclusions In our study, patients with lower post-PCI value were independently associated with higher risk of cardiovascular adverse events.

Pattern of Musculoskeletal Manifestation in Patient with Diabetes Mellitus

Background: Diabetic mellitus (DM) both type 1 and type 2 increasing dramatically throughout worldwide. DM involved all the vital organs including musculoskeletal system. Objective: The purpose of study was to find out patterns of musculoskeletal manifestation (MSM) in diabetic patients &amp; to find out a strategy to improve the outcome of the MS complications in patients with Diabetes Mellitus. Material and Methods: This was hospital based observational study conducted on 143 diabetics patients with musculoskeletal manifestations, both men and women (aged e”15- 70 years) visited in outpatient department and hospital admitted patient in a tertiary care of teaching hospital. Patterns were defined by a meticulous history, relevant general and systemic examination &amp; with the aid of musculoskeletal (MS) Function Assessment semi structured Questionnaire. Results: MSM are common among patients with type 2 diabetes Out of 143 patients in our study 103(72.03%) were Male and 40(27.97%) were female, and male –female ratio 2.57:1. The age distribution of study patients was 15 to 70 years. Overall, 72.03.% of patients were among the 40-59 years old and about 20.28% were 60 years and mean age of the patients was 55±5. Above which is statistically significant (P= 0.048). The shoulder involvement as adhesive capsulitis (frozen shoulder) was found among 69(48.25%) on the diabetic cohort and statistically significant (P= &lt;.05) and mostly among the housewife (27.99%) and manual worker like cultivator (13.99%). Degenerative osteoarthritis was commonly associated with MSM with DM than inflammatory arthritis. Conclusion: In our study shows degenerative, non-inflammatory MSM are common among the diabetic patients that leads to significant pain and disability that directly related with poor glycemic control and co-morbidities like stroke and obesity. Early recognition of these complications, and multidisciplinary management between diabetes and rheumatology specialists is necessary to reduce morbidity. EWMCJ Vol. 12, No. 1&amp;2, January-July 2024: 66-69

Obesity plays a key role in inducing myocardial and vascular dysfunction in a translational model of heart failure with preserved ejection fraction in rats

Abstract Background Exploring experimental models of heart failure with preserved ejection fraction (HFpEF) may help to understand the mechanisms leading to this challenging condition. Purpose In a translational model, we aimed to assess the relative contribution of hypertension and obesity in inducing structural, functional and hemodynamic changes associated to the HFpEF phenotype. Methods We investigated 3 groups of male 40 weeks old rats: control Wistar Kyoto (WKY, n=10), Spontaneous Hypertensive Rats (SHR, n=10) and SHR with obesity induced by consumption of cafeteria diet during 28 weeks (Ob-SHR, n=9). Animals were submitted to assessment of: body weight, systolic (SBP) and diastolic (DBP) blood pressure; in vivo structural and functional changes evaluated by high resolution Echocardiography including left atrial dimension (LA), left ventricle (LV) diastolic dimension (LVDD), LV posterior wall thickness (LVPW), LV wall relative thickness (LVWRT), LV ejection fraction (LVEF). Invasive hemodynamic evaluation assessed the intraventricular pressure curves obtaining LV end diastolic pressure (LVEDP) and calculation of LV diastolic time constant (Tau). After euthanasia, thoracic aorta was used for vascular function assessment by measuring the maximal cumulative concentration-effect curves of contraction to phenylephrine (PE), expressed as Emax (%). Protein expression of Intercellular Adhesion Molecule 1 (ICAM-1) was determined in myocardial tissue (% in relation to WKY). Results were expressed as mean ± SEM and effects of groups vs time were compared with mixed ANOVA. Results The results are shown in the table. We observed higher levels of SBP and DBP in SHR and Ob-SHR when compared to WKY, but with similar values between SHR and Ob-SHR groups. Regarding the structural LV changes, we observed LV remodeling and LA dilation in both SHR and Ob-SHR groups, but with no difference between both hypertensive groups. The Ob-SHR was the only group showing increased LVEDP in comparison to other groups. The Tau was also increased in the Ob-SHR animals. Concordantly, the Ob-SHR group showed increased expression of ICAM-1 (figure - A) that was concomitant to abnormal vascular response with increased contraction to PE (figure - B) as compared to SHR and WK groups. Conclusions In this translational model of HFpEF in rats, the structural changes related to LV remodeling were similar in SHR and Ob-SHR, probably reflecting comparable higher levels of blood pressure observed in both groups. In contrast, elevated EDP, a hallmark of HFpEF, was only seen in the Ob-SHR group and this was concomitant to diastolic dysfunction, endothelial inflammatory activation and altered vascular function. Our results indicate that obesity is a key factor inducing vascular and myocardial changes that triggers HFpEF phenotype in this model.

Intracoronary nicardipine to induce hypaeremia

Abstract Background Several pharmacological agents and routes of administration have been used to induce transient maximal hyperaemia, but most suffer from shortcomings that limit their clinical usage. Nicardipine, a dihydropyridine calcium channel blocker, has been proposed as a coronary hyperaemic agent with the advantage of not causing any adverse effects. Purpose We compared intracoronary (IC) nicardipine with IC papaverine for obtaining fractional flow reserve (FFR) and pullback pressure gradient (PPG). Methods and results This is a prospective, single-center study enrolling stable patients presenting with intermediate coronary artery disease (CAD) undergoing invasive functional assessment. The lowest FFR, duration of the hyperemic plateau, and PPG were assessed after IC nicardipine (400 µg to the left coronary or 300 µg to the right coronary artery) and IC papaverine (12 mg to the left coronary artery and 8 mg to the right coronary artery). Results Overall, 107 patients with 108 vessels (216 FFR and 216 PPG paired measurements) were analyzed. The correlation in FFR between nicardipine and papaverine was r = 0.95 (95% CI 0.92 to 0.96, p &amp;lt; 0.001) with a mean difference of 0.02 FFR units (limit of the agreement [LOA]: -0.04 to 0.08). Similarly, the correlation in PPG between nicardipine and papaverine was r = 0.86 (95% CI 0.71 to 0.93, p &amp;lt; 0.001) with a mean difference of 0.01 PPG units (limit of the agreement [LOA]: -0.14 to 0.17). The hyperaemic plateau was significantly longer with nicardipine (101.4 ± 62.1 s nicardipine vs 41.5 ± 14.3 s papaverine, p &amp;lt; 0.001). No significant differences were observed in the magnitude of changes in blood pressure and heart rate (p=NS). No complications occurred with the administration of IC nicardipine or papaverine. Conclusion FFR and PPG values obtained following nicardipine administration exhibited excellent agreement with those obtained using papaverine. Moreover, the hyperaemic response induced by nicardipine led to a significantly prolonged steady state in comparison to papaverine. Given its widespread availability, cost-effectiveness, safety profile and frequent utilization in clinical settings, nicardipine emerges as the optimal vasodilator for coronary physiology testing.FFR by Nicardipine vs PapaverinePPG by Nicardipine vs Papaverine

Index of microvascular resistance (IMR) and fractional flow reserve (FFR) relationship in patients with angina and non-obstructive coronary artery (ANOCA) disease

Abstract Background Despite the plausible physiological connection between the index of microvascular resistance (IMR) and fractional flow reserve (FFR), a comprehensive understanding of their correlation is lacking. Purpose This study aims to elucidate the association between IMR and FFR in patients presenting with angina and non-obstructive coronary artery disease, employing various IMR threshold values. Methods Consecutively enrolled patients with angina and non-obstructive coronary artery disease underwent a thorough functional assessment encompassing both epicardial (Pd/Pa, FFR) and microvascular (coronary flow reserve, CFR; IMR) domains by the thermodilution technique. The hyperemic response to adenosine (Δ) was quantified as the disparity between Pd/Pa and FFR. Correlations between FFR and IMR, as well as between Δ and IMR, were examined globally and categorized based on the presence of coronary microvascular dysfunction (CMD, CFR&amp;lt;2). Subsequently, patients were stratified into three groups based on IMR values: Group 1 (IMR&amp;lt;25), Group 2 (25≤IMR&amp;lt;40), and Group 3 (IMR ≥ 40). Further analyses of adenosine hyperemic response, IMR, and FFR correlations were conducted within each group. Results A total of 116 patients and lesions were evaluated, with 71 in Group 1, 32 in Group 2, and 13 in Group 3. Globally, FFR showed no correlation with IMR (r = 0.025, p = 0.788), regardless of CMD presence (CMD, r = 0.210, p = 0.325; no CMD r = -0.051, p = 0.631). Same results were observed for the relationship of hyperemic response to adenosine and IMR (r = -0.0398, p = 0.673). However, upon stratification by IMR values, only patients in Group 3 exhibited a positive correlation between FFR and IMR (r = 0.580, p = 0.037), with a notable reduction in the hyperemic response to adenosine as IMR values increased (r = -0.5485, p = 0.052). After adjusting for potential confounding factors, a significant increase of 0.01 in FFR values was observed for every 10-unit rise in IMR (p = 0.045) in this Group. Conclusions FFR appears to be particularly influenced by elevated IMR values (≥40). Prudent interpretation of FFR values in such instances is imperative, especially in cases of functionally borderline epicardial stenosis.

Left atrial function for predicting atrial fibrillation: a machine learning approach

Abstract Background Common risk scores for atrial fibrillation (AF) are based on clinical risk factors, and little is known about the contribution of left atrial (LA) function parameters to risk assessment. Purpose To determine whether a machine learning-based model that includes LA function parameters outperforms a commonly used risk scores, the CHARGE-AF, in predicting AF. Methods Participants in the Atherosclerosis Risk in Communities (ARIC) Study (a community-based cohort study in the USA) who attended visit 5 (2011-2013) and without a history of AF were included in this analysis. Incident AF was ascertained from ECG during study visits, hospitalization discharge codes, and death certificates. Random survival forest methodology was used to build a prediction model for AF; candidate variables included traditional clinical risk factors and measures of LA structure and function. Dataset was randomly split into a training (75%) and testing (25%) cohort. For each variable, importance was measured based on the reduction in Harrell’s c-statistic if the variable was randomly permuted prior to obtaining predicted values. Variables significantly associated with AF were included in the final model. Model calibration was tested using the Greenwood-Nam-D'Agostino (GND) test. Discrimination ability of our model was assessed in the testing cohort using Harrell’s c-statistic and compared with that of the CHARGE-AF model. Results 4,909 participants (59% female, 22% Black, mean age 75 years) were included. During a median follow-up of 7.0 years (1st-3rd quartile: 5.4-7.8), 650 participants developed AF. Variables significantly associated with incident AF were race, triglycerides, systolic blood pressure, coronary heart disease, age, LA maximal volume index, NT-proBNP, and LA reservoir strain (Figure 1). LA reservoir strain was the variable most strongly associated with AF. The final model showed good discrimination (c-statistic (95% CI): 0.734 (0.698-0.768)). The GND test did not detect statistically significant miscalibration (GND p=0.08). Compared with our model, CHARGE-AF had lower discrimination ability (c-statistic (95% CI): 0.635 (0.594-0.677)) and the difference was statistically significant (difference in c-statistic (95% CI): 0.099 (0.043-0.152)). Conclusion A machine learning-based model with few variables including LA function outperforms a commonly used risk model in predicting AF. Incorporation of LA functional assessment may help inform clinicians regarding individual risk of AF.

A novel murine model of stress-induced cardiomyopathy achieved by chemogenetic stimulation of the locus coeruleus-norepinephrine system

Abstract Background Takotsubo syndrome (TTS) is a stress-induced acute cardiomyopathy characterized by transient left ventricular (LV) dysfunction without obstructive coronary artery disease. TTS is often underdiagnosed and undertreated and typically occurs in middle-aged women who recover from initial symptoms within a few weeks. Despite the apparent recovery, TTS patients have a worse cardiovascular prognosis compared to healthy individuals. To date, the pathophysiology underlying TTS remains unclear. So far, preclinical models barely reflect the complete clinical picture of TTS observed in humans. Moreover, these models display several limitations, e.g., high mortality or disregarding the involvement of the central nervous system. Consequently, much of the current obscurity concerning the pathophysiology of TTS is due to the lack of appropriate preclinical models. Purpose The present study aimed to assess whether chemogenetic activation of the locus coeruleus-(LC)-norepinephrine-(NE) system in vivo can induce LV dysfunction similar to that observed in patients with TTS. For this purpose, we used the designer excitatory receptor activated exclusively by designer drug (DREADD) system. Methods 11-13 weeks-old female Cre-dependent DREADD mice were genetically modified to express a codon-improved Cre recombinase under the dopamine-beta-hydroxylase-(DBH) promoter. For this purpose, a designed excitatory receptor exclusively activated by designer drugs or a control vector was stereotactically delivered to the LC using adenoviral transfection. Restricted expression of DBH-positive noradrenergic neurons to the LC was validated using pupillometry. LC-NE was activated by administering low-dose clozapine 0.03 mg/kg/day intraperitoneally. Serial anatomical and functional assessments of the cardiac phenotype in these mice were performed at baseline, the end of stress induction, and after ten days and three months of the recovery phase using echocardiography and cardiac magnetic resonance imaging. Results Targeted stimulation of the LC-NE system resulted in apical LV wall motion abnormality in 70–83% of mice. A complete recovery of LV wall motion abnormality was observed after the recovery phase. Conclusions Chemogenetic stimulation of the LC-NE system in mice mimics LV wall abnormalities similar to those observed in patients with TTS and may, therefore, be a novel preclinical model to investigate the pathophysiology of TTS.

Central Pulse Wave Velocity and Augmentation Index Are Repeatable and Reproducible Measures of Arterial Function.

Arterial function (specifically arterial stiffness) is an important cardiovascular risk factor. Pulse wave velocity (PWV) and augmentation index (Al ) are established indicators of arterial function. The present study aimed to evaluate the repeatability and reproducibility of PWV and Al in healthy individuals. Forty healthy participants (age 33 ± 11 years, 17 females) underwent resting supine PWV and Al assessments. Measurements were made in triplicate and repeated 1 week apart. Al was measured by brachial occlusion and PWV was measured from the carotid artery to the femoral artery via the tonometer-oscillometric method. Repeatability and reproducibility were assessed using the intraclass correlation coefficient (ICC). Interoperator reproducibility was performed on 10 participants. The average values for week-to-week visits for PWV and Al were 6.20 ± 0.91 versus 6.13 ± 0.91 ms-1 and 14.0 ± 11.8 versus 16.3 ± 12.2% respectively. For same-day measurements, both PWV and Al showed excellent repeatability (PWV: ICC = 0.96, 95% CI: 0.92-0.98, p < 0.01; Al : ICC = 0.90, 95% CI: 0.84-0.94, p < 0.01) and interoperator reproducibility (PWV: ICC = 0.98, 95% CI: 0.93-1.00, p < 0.01; Al : ICC = 0.93, 95% CI: 0.69-0.98, p < 0.01). Measurements were repeated 1 week apart and showed good reproducibility (PWV: ICC = 0.77, 95% CI: 0.61-0.87, p ≤ 0.01; Al : ICC = 0.73, 95% CI: 0.73-0.86, p < 0.01). PWV and Al demonstrate excellent repeatability and good reproducibility. Considering these variables are noninvasive and easy-to-measure, arterial function assessment may have a role in routine clinical practice to facilitate risk stratification in cardiovascular diseases.

Impact of preoperative quantitative flow ratio on long term coronary artery bypass grafts patency

Abstract Background Preoperative fractional flow reserve (FFR) in the native coronaries is a known predictor of long-term graft patency after coronary artery bypass graft (CABG) surgery. Quantitative flow ratio (QFR) is an angiogram-based functional assessment tool of coronary stenoses. Its predictive value of graft patency is unknown. Purpose To investigate the impact of preoperative QFR value on long-term graft patency after CABG. Methods In this retrospective multicentric study we included consecutive patients treated with CABG between 2011 and 2022, with available coronary angiogram before and at any timepoint after CABG. Three-vessel QFR analysis of the preoperative angiography has been performed. Follow-up angiography was checked for graft patency. Only vessels entered the analysis for which baseline QFR was appropriate and which has been bypassed. Results 400 patients were included with mean age of 67±8 years. They received on average 2.0±0.9 bypasses. 788 coronaries and bypasses were analyzed, among the latter 455 were arterial and 333 were veins. 37% were placed on LAD, 26% on RCA and 26% on the LCx. Stenosis severity at baseline was 73±22% with a QFR value of 0.68±0.30. Follow-up angiographies were performed at 34±29 months. Overall graft patency was 83%, with higher occlusion rate for venous than arterial conduits (27% vs 9%, respectively; HR 3.9 [2.60-5.88]). Occlusion rate was lower for grafts implanted on QFR significant native vessels versus those, placed on non-significant ones (13% vs 30%, respectively; HR 2.86 [1.93-4.26]). Benefit was maintained for both, arterial (5% vs 22%, respectively; HR 5.23 [2.78-10.38]), as well as for venous conduits (24% vs 39%; HR 2.09 [1.21-3.50]). Conclusion QFR significantly predicts graft patency irrespective of whether the graft is arterial or venous. However, patency of venous grafts is poor, even if implanted on functionally significant native stenotic coronaries.Graft patency

Microvascular functional assessment using microvascular resistance reserve in patients undergoing elective fractional flow reserve-guided percutaneous coronary intervention

Abstract Background Microvascular resistance reserve (MRR) has been proposed as an index for coronary microvascular function. However, the determinants of MRR and the prevalence of coexistent coronary microvascular dysfunction (CMD) in patients with obstructive coronary disease remains elusive. We sought to assess the prevalence of CMD and determinants for MRR. Methods We retrospectively investigated 703 physiologically significant (FFR≤0.80) chronic lesions in our institutional physiological registry. All patients underwent pre-PCI physiological assessment including FFR, CFR and MRR. CMD was defined with MRR&amp;lt;2.1. The characteristics and physiological findings were compared between CMD and non-CMD. The predicting factors for CMD were investigated. Results In a total cohort, FFR, CFR and MRR were 0.70(0.6-0.75), 1.82 (1.27-2.80) and 3.20 (2.22-4.30), respectively. CMD was observed in 142 (20.2%) vessels. Older age (71[65-77] vs 69[62-75], p=0.007), female patients (24.6% vs 14.4%, p=0.005) and non-LAD culprit lesions (42.3% vs 32.4%, p=0.014) were significantly more frequent in CMD. Furthermore, CMD group was significantly associated with the history of hemodialysis and heart failure (10.6% vs 3.6%, p=0.001, 38.0% vs 31.0%, p=0.015 respectively). FFR and CFR were lower in CMD than non-CMD (0.67[0.60-0.73] vs 0.70[0.61-0.76], p&amp;lt;0.001, 1.03[0.82-1.21] vs 2.16[1.56-3.00], p&amp;lt;0.001, respectively). In multiple linear regression analysis, low FFR, non-LAD lesion, older age, female and history of hemodialysis were significant predictors for the presence of CMD. Conclusion The prevalence of coexistent CMD in patients undergoing PCI was 20.2%, when defined as MRR≤2.1. Non-LAD lesion location, older age, women, history of hemodialysis, and FFR were significantly associated with the presence of CMD.

Unveiling the prognostic journey: renal function trajectories in 'de novo' heart failure with reduced ejection fraction - insights from a cohort study and their impact on patient outcomes

Abstract Background HFrEF poses significant clinical challenges globally. Renal dysfunction frequently coexists with HF, exacerbating prognosis. However, the dynamic trajectory of renal function in 'de novo' HFrEF patients and its prognostic implications remain understudied. Methods We conducted a prospective cohort study involving 370 'de novo' HFrEF patients. Renal function was initially assessed upon admission and re-evaluated at the end of the titration period. The CKD-EPI formula was used for renal function assessment. Patients were followed up for a median of 15 months. Statistical analyses were performed to evaluate predictors of adverse outcomes. Results Baseline renal function significantly influenced outcomes, with eGFR &amp;lt; 45 ml/min associated with higher mortality and heart failure readmissions. Among patients with available renal function data at discharge (n=354), 87 (24.6%) had eGFR &amp;lt; 45 ml/min, while 267 (72.2%) ≥ 45 ml/min. Patients with eGFR &amp;lt; 45 ml/min exhibited older age, higher prevalence of comorbidities, lower haemoglobin levels, and higher creatinine and NT-proBNP levels, both at admission and discharge. Furthermore, they were less likely to receive certain heart failure medications at discharge. During follow-up, 46 deaths (13.0%) and 105 events of combined all-cause death and readmission due to heart failure (29.6%) occurred. Patients with eGFR ≥ 45 ml/min exhibited a lower overall mortality (HR: 0.29, p &amp;lt; 0.001) and all-cause death and heart failure readmissions (HR: 0.32, p &amp;lt; 0.001) both in univariate and multivariate analysis (HR: 0.63, p = 0.028 for mortality; HR: 0.53, p = 0.038 for combined endpoint). See Figure 1. Among patients with available renal function data at follow-up (n=304), 240 (78.9%) had eGFR ≥ 45 ml/min (stabilization or improvement), and 64 (21.1%) had eGFR &amp;lt; 45 ml/min (deterioration or previously &amp;lt; 45 ml/min). Patients with eGFR &amp;lt; 45 ml/min at follow-up exhibited older age, lower BMI, higher prevalence of comorbidities, lower haemoglobin levels, and higher NTproBNP levels at admission and discharge. They were also less likely to receive certain crucial heart failure medications at discharge and follow-up (Table 1). During follow-up, 31 deaths (10.1%) and 87 events of combined death and readmission due to heart failure (38.6%) occurred. In univariate analysis, patients with eGFR ≥ 45 ml/min exhibited a lower overall mortality (HR: 0.27, p &amp;lt; 0.001) and admissions (HR: 0.30, p &amp;lt; 0.001), which remained significant in multivariate analysis (HR: 0.43, p = 0.048 for mortality; HR: 46, p = 0.014 for admissions). See Figure 1. Conclusion Our findings underscore the importance of integrated heart-kidney care in 'de novo' HFrEF patients. Continuous monitoring of renal function and interventions to prevent deterioration are crucial for optimizing outcomes. Further research is needed to validate these findings and explore targeted therapeutic strategies for renal protection in HFrEF.

CD14 blockade preserves left ventricular structure and systolic function in a murine model of ST-elevation myocardial infarction

Abstract Background Cluster of differentiation-14 (CD14) facilitates the excessive pro-inflammatory monocyte-macrophage response to myocardial injury. Both acute and chronic infiltration of pro-inflammatory macrophages are implicated in the immunological progression of ischemic heart failure. However, investigation of clinically practicable strategies of CD14 blockade are yet to be reported. Purpose This fully blinded and randomised preclinical study evaluated the efficacy of a neutralising anti-CD14 antibody given at reperfusion in a murine model of reperfused ST-elevation myocardial infarction (STEMI) with key clinical features. Methods Large anterior STEMI was induced in 48 adult mice by left anterior descending coronary artery occlusion for 1 h prior to reperfusion and randomisation to receive anti-CD14 antibody, isotype control (IgG2a) or saline weekly for four weeks (independently blinded). Outcome measures included functional assessments by 9.4T cardiac magnetic resonance (CMR) imaging and ultra-high-resolution echocardiography at 21- and 28-days post-STEMI, respectively. Results Multi-plane short axis CMR at 21-days post-STEMI revealed greater left ventricular (LV) ejection fraction in the anti-CD14 antibody-treated group compared with saline- and isotype-treated controls (30±1 vs 19±1 and 20±1 %, respectively, p&amp;lt;0.001; Figure 1A). CMR also revealed reduced LV dilatation with anti-CD14-treatment compared to control groups (76±5 vs 102±8 and 107±7 µl EDV in saline- and isotype-treated controls, respectively, p&amp;lt;0.05). Parasternal long axis echocardiography at 28 days post-STEMI confirmed that anti-CD14 antibody treatment was associated with greater LV systolic function compared to saline and isotype controls (30±1 vs 24±1 and 25±2 % EF, respectively, p&amp;lt;0.05; Figure 1B). Preservation of LV end-diastolic (86±4 vs 111±6 and 101±5 µl, p&amp;lt;0.01) and end-systolic (61±3 vs 84±5 and 77±5 µl, p&amp;lt;0.01) volumes was also observed with anti-CD14 treatment. Global longitudinal strain (GLS) of the LV was also significantly greater at 28 days post-STEMI with anti-CD14 treatment relative to saline and isotype controls (-8.5±0.4 vs -6.8±0.3 and -6.6±0.4 %, respectively, p&amp;lt;0.05). Conclusion(s) The findings of this fully blinded and randomised preclinical study provide evidence of a clinically practicable strategy of CD14 blockade initiated at reperfusion to mitigate progressive LV systolic dysfunction and dilatation post-STEMI.Figure 1.Functional outcome measures