Myocardial Demand Research Articles

"Coke in the Dope": The Underrecognized Complications of a Cocaine-Adulterated Fentanyl Supply.

The opioid crisis, particularly the "fourth wave" involving fentanyl and stimulants, has been responsible for an alarming increase in overdose deaths in the United States. Although fentanyl contamination in cocaine has gained significant attention, the converse-cocaine-adulterated fentanyl-has been largely overlooked despite its health implications. The rise in concurrent cocaine and fentanyl overdose deaths could be attributed to various factors, from intentional polysubstance use to unintentional adulterations. Cocaine-related health issues may amplify the problem. Four potential pathways for the increased risk of overdose with cocaine-adulterated opioids include enhanced drug reinforcement, potential overdose risk with switching drug samples, altered metabolism of medications used for opioid use disorder, and increased myocardial demand juxtaposed with opioid-induced respiratory depression. With these risks, the importance of drug testing becomes paramount in the unregulated drug market. As polysubstance use overdoses surge, there is an urgent need to understand how drug supplies are changing in order to effectively identify appropriate harm reduction strategies. Specifically, further research is needed evaluating complications of low-level cocaine exposure with chronic/persistent opioid use. The hazards associated with cocaine-adulterated fentanyl emphasize the significance of understanding not only fentanyl's presence in cocaine but also cocaine's role in the fentanyl supply.

Influence of home-based heat therapy on thermal and cardiovascular strain during passive heat exposure in older adults

Heat waves are occurring more frequently and with greater intensity. In fact, 2023 marked the hottest summer ever recorded in the Northern Hemisphere. Heat waves increase the risk for heat-related morbidity and mortality, particularly for older adults who have a reduced ability to dissipate heat. Heat acclimation induces physiological adaptations that attenuate thermal and cardiovascular strain during subsequent heat exposures. However, traditional heat acclimation protocols require expensive equipment (e.g., climate chamber) and may be challenging for older adults with limited functional capacity. Home-based heat therapy provides a potentially safe and pragmatic option to induce heat acclimation. The purpose of this pilot study was to test the hypothesis that home-based heat therapy reduces thermal and cardiovascular strain in older adults during acute passive heat exposure. Six older adults (5 women; 67 ± 4 years) performed 8 weeks of home-based heat therapy by immersing their lower legs ~33 cm into a heated (~ 42°C) and circulated water bath 4 days per week, for 45 min per session. Intestinal temperature (telemetric pill) and heart rate were assessed before (pre) and after (post) the intervention during acute heat exposure (45 min lower leg water immersion). In addition, rate pressure product, an estimate of myocardial demand, was calculated as heart rate x systolic blood pressure. Resting intestinal temperature, heart rate, and rate pressure product did not differ from pre to post heat therapy (all P ≥ 0.6). However, the change in intestinal temperature during acute heat exposure was reduced after heat therapy (15 min: pre, Δ0.47 ± 0.17 °C vs. post, Δ0.33 ± 0.14 °C; 30 min: pre, Δ0.84 ± 0.29 °C vs. post, Δ0.72 ± 0.23 °C; 45 min: pre, Δ1.10 ± 0.27 °C vs. post, Δ1.07 ± 0.24 °C; P = 0.03 for main effect of time). Likewise, the change in heart rate was attenuated following the intervention (15 min: pre, Δ14 ± 9 bpm vs. post, Δ10 ± 5 bpm; 30 min: pre, Δ22 ± 13 bpm vs. post, Δ17 ± 6 bpm; 45 min: pre, Δ25 ± 9 bpm vs. post, Δ21 ± 6 bpm; P = 0.02 for main effect of time). Rate pressure product was also reduced following heat therapy (15 min: pre, Δ1280 ± 1636 bpm·mmHg vs. post, Δ322 ± 698 bpm·mmHg; 30 min: pre, Δ1800 ± 1573 bpm·mmHg vs. post, Δ1170 ± 450 bpm·mmHg; 45 min: pre, Δ2145 ± 593 bpm·mmHg vs. post, Δ840 ± 602 bpm·mmHg; P < 0.01 for main effect of time). Our preliminary data suggest that 8 weeks of home-based heat therapy elicits some adaptations that may reflect heat acclimation. However, further work is needed to confirm these initial findings. American Heart Association TPA958179. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Determining the Frequency of Non-Obstructive Coronary Artery Disease in Elective Angiography Cases

Cardiovascular disease particularly ischemic heart disease has emerged as a leading cause of death. Atherosclerosis in epicardium results in CAD without the restriction of coronary circulation but the other processes that may disrupt the myocardial supply and demand in patients exhibiting angina symptoms or indications may be suspected of having non-obstructive CAD. Objective: To find out the prevalence of non-obstructive CAD in patients enrolled for elective angiography. Methods: A cross-sectional descriptive analysis was done in the Cardiology department in King Edward Medical University and Mayo Hospital, Lahore. The duration of study was for six months from 01-08-2022 to 01-02-2023. After approval from hospital ethical committee, 150 patients were enrolled in the study with informed written consent. Demographics including Name, age, BMI, confounding factors like (diabetes, hypertension, smoking and family history) and address were noted. All selected patients underwent coronary angiography via right femoral artery approach by a consultant cardiologist. Non-obstructive coronary artery disease was assessed as per operational definition. All the information was noted on pre-designed proforma (attached). Results: A total of 150 patients were selected for the study. It showed that out of 150 patients, 2.7% (n=4) fall in age group of 18-40 years and 97.3 % (n=146) were in age group of 41-60 years, average age was 51.94±5.26 years and the BMI was 27.96±6.44 kg/m2. There were 62.7 % (n=94) male and 37.3 % (n=56) females. Frequency of diabetes mellitus was 34.7 % (n=52), hypertension was 24.7 % (n=37), smokers 16.7 % (n=25), family history was 12.7 % (n=19) and frequency of non-obstructive CAD was 27.3 % (n=41). Conclusions: It is to be concluded that a considerable percentage of patients enrolled for elective coronary angiography had non-obstructive CAD.

Quantitative 17 O MRSI of myocardial oxygen metabolic rate, blood flow, and oxygen extraction fraction under normal and high workload conditions.

The heart is a highly aerobic organ consuming most of the oxygen the body in supporting heart function. Quantitative imaging of myocardial oxygen metabolism and perfusion is essential for studying cardiac physiopathology in vivo. Here, we report a new imaging method that can simultaneously assess myocardial oxygen metabolism and blood flow in the rat heart. This novel method is based on the 17 O-MRSI combined with brief inhalation of 17 O-isotope labeled oxygen gas for quantitative imaging of myocardial metabolic rate of oxygen consumption (MVO2 ), myocardial blood flow (MBF), and oxygen extraction fraction (OEF). We demonstrate this imaging method under basal and high workload conditions in rat hearts at 9.4 T. We show that this 17 O MRSI-based approach can directly measure and image MVO2 (1.35-4.06 μmol/g/min), MBF (0.49-1.38 mL/g/min), and OEF (0.33-0.44) in the heart of anesthetized rat under basal and high workload (21.6 × 103 -56.7 × 103 mmHg • bpm) conditions. Under high workload condition, MVO2 and MBF values in healthy rats approximately doubled, whereas OEF remained unchanged, indicating a strong coupling between myocardial oxygen metabolic demand and supply through blood perfusion. The 17 O-MRSI method has been used to simultaneously image the myocardial metabolic rate of oxygen consumption, blood flow, and oxygen extraction fraction in small animal hearts, which are sensitive to the physiological changes induced by high workload. This approach could provide comprehensive measures that are critical for studying myocardial function in normal and diseased states and has a potential for translation.

Increased inflammatory proteins in patients with severe obesity is associated with persistent myocardial dysfunction one year after bariatric surgery. The FatWest study

Abstract Background Over half of patients with severe obesity have subclinical cardiac dysfunction and about 40% maintain impaired left ventricular (LV) mechanics one year after bariatric surgery despite impressive weight reduction. Purpose To investigate whether measurement of serum markers of chronic inflammation before bariatric surgery can help identify patients with persistent postoperative cardiac dysfunction. Methods In the prospective FatWest (Bariatric Surgery on the West Coast of Norway) study 75 patients with severe obesity (44±9 years, 72% women, body mass index [BMI] 41.5±4.7 kg/m², 56% with hypertension) underwent echocardiography before and 1 year after Roux-en-Y gastric bypass surgery. We assessed LV mechanics in the radial and longitudinal direction by the midwall shortening (MWS) and global longitudinal strain (GLS). Myocardial oxygen (O2) demand was derived from the LV mass-wall stress-heart rate product. Inflammation was assessed by high-sensitive C-reactive protein, serum amyloid A and calprotectin in biobank samples. Results Preoperatively, patients with low MWS (45% of the group) had increased high-sensitive C-reactive protein, total calprotectin, and several amyloid A isoforms, and patients with high myocardial O2 demand (20%) had high total calprotectin (all p<0.05). In the whole study population, bariatric surgery induced a significant improvement in both BMI (12.6±3.7 kg/m²), GLS (4.74±5.20%), myocardial O2 demand and inflammatory proteins (Figure A, all p<0.001). However, there were no significant improvement in MWS, and 33% of patients still had low MWS at the 1-year control. In logistic regression analyses, after adjustment for sex, BMI and hypertension, increased preoperative serum total calprotectin was independently associated with high myocardial O2 demand both pre- and postoperatively (Nagelkerke R² 0.47 and 0.51, p<0.05). In similar analyses, higher preoperative serum total amyloid A was related to low MWS and high myocardial O2 demand 1 year after surgery (Nagelkerke R² 0.55 and 0.51, p<0.05). A simple preoperative risk score based on sex, hypertension, biplane ejection fraction, and serum total amyloid A above 4.0 mg/ml predicted low 1-year MWS with 79% sensitivity and 75% specificity at a value of 1.75 in Receiver Operating Characteristic (ROC) analysis (AUC 0.80, p<0.001) (Figure B). Low GLS was not predicted by inflammatory biomarkers at any timepoint. Conclusion Increased serum concentration of inflammatory proteins in patients with severe obesity is linked to persistently elevated myocardial O2 demand and impaired LV midwall mechanics 1 year after bariatric surgery.Figure AFigure B

Abstract 13787: Restricted Coronary Flow Reserve of Mental Stress Induced Myocardial Ischemia in Angina and No Obstructive Coronary Artery Disease

Background: The myocardial blood flow (MBF) mechanism in mental stress-induced myocardial ischemia (MSIMI) in angina with no obstructive coronary artery disease (ANOCA) population is unknown. Methods: 13-NH 3 cardiac PET-CT was utilized to assess MBF and perfusion changes under mental stress (ms) and adenosine stress (as) in ANOCA subjects and gender- and age-matched healthy controls. MSIMI was defined as an increase in perfusion defect score of ≥3 points. Results: Among the 126 participants enrolled, ANOCA women showed a significantly higher prevalence of MSIMI compared to the healthy controls (36/84 vs. 1/42, p <0.001). Perfusion defects under ms occurred synchronously however more pronounced in the left anterior descending and right coronary artery territories, consistent with a significantly higher MBF hyperemia in the left circumflex territory. MBF ms shows a close correlation with rate-pressure product (RPP ms ) ( p <0.05 in ANOCA&MSIMI+, ANOCA&MSIMI-, and control groups with r pearson ranging from 0.39-0.65). Although no differences existed in absolute MBF ms values between groups, there were notable increasing trends among the three groups in corrected MBF, which reflected blood flow supply-demand balance (ANOCA&MSIMI+: 0.96±0.23 vs. control group: 1.10±0.29, p =0.020), and in coronary flow reserve (CFR) (ANOCA&MSIMI+: 2.41±0.75 vs. control group: 2.89±0.77, p =0.016). Furthermore, after adjusting for confounding factors, only subjects in ANOCA&MSIMI+ group did not exhibit a corresponding increase in MBF ms matching MBF as . Conclusion: Restricted CFR, indicating impaired coronary microvascular function, and mismatch between myocardial blood supply and demand together constitute the pathogenic mechanism of MSIMI in ANOCA population. More researches are still needed in exploring the brain-heart interaction in MSIMI.

Shengxian decoction protects against chronic heart failure in a rat model via energy regulation mechanisms

BackgroundChronic heart failure (CHF) is actually a disease caused by an imbalanced energy metabolism between myocardial energy demand and supply, ultimately resulting in abnormal myocardial cell structure and function. Energy metabolism imbalance plays an important role in the pathological process of chronic heart failure (CHF). Improving myocardial energy metabolism is a new strategy for the treatment of CHF. Shengxian decoction (SXT), a well-known traditional Chinese medicine (TCM) formula, has good therapeutic effects on the cardiovascular system. However, the effects of SXT on the energy metabolism of CHF is unclear. In this study, we probed the regulating effects of SXT on energy metabolism in CHF rats using various research methods.MethodsHigh-performance liquid chromatography (HPLC) analysis was used to perform quality control of SXT preparations. Then, SD rats were randomly assigned into 6 groups: sham, model, positive control (trimetazidine) and high-, middle-, and low-dose SXT groups. Specific reagent kits were used to detect the expression levels of ALT and AST in rats’ serum. Echocardiography was used to evaluate cardiac function. H&E, Masson and TUNEL staining were performed to examine myocardial structure and myocardial apoptosis. Colorimetry was used to determine myocardial ATP levels in experimental rats. Transmission electron microscopy was used to observe the ultrastructure of myocardial mitochondria. ELISA was used to estimate CK, cTnI, and NT-proBNP levels, and LA、FFA、MDA、SOD levels. Finally, Western blotting was used to examine the protein expression of CPT-1, GLUT4, AMPK, p-AMPK, PGC-1α, NRF1, mtTFA and ATP5D in the myocardium.ResultsHPLC showed that our SXT preparation method was feasible. The results of ALT and AST tests indicate that SXT has no side effect on the liver function of rats. Treatment with SXT improved cardiac function and ventricular remodelling and inhibited cardiomyocyte apoptosis and oxidative stress levels induced by CHF. Moreover, CHF caused decrease ATP synthesis, which was accompanied by a reduction in ATP 5D protein levels, damage to mitochondrial structure, abnormal glucose and lipid metabolism, and changes in the expression of PGC-1α related signal pathway proteins, all of which were significantly alleviated by treatment with SXT.ConclusionSXT reverses CHF-induced cardiac dysfunction and maintains the integrity of myocardial structure by regulating energy metabolism. The beneficial effect of SXT on energy metabolism may be related to regulating the expression of the PGC-1α signalling pathway.

Coronary microvascular dysfunction in heart failure patients.

Coronary microcirculation has multiple layers of autoregulatory function to maintain resting flow and augment hyperemic flow in response to myocardial demands. Functional or structural alterations in the coronary microvascular function are frequently observed in patients with heart failure with preserved or reduced ejection fraction, which may lead to myocardial ischemic injury and resultant worsening of clinical outcomes. In this review, we describe our current understanding of coronary microvascular dysfunction in the pathogenesis of heart failure with preserved and reduced ejection fraction.

A Systematic Review of COVID-19 Impact on Cardiovascular Diseases

Background: The world is confronted with the threat of a pandemic driven by a novel coronavirus, namely Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The disease was spread in December 2019 in Wuhan (China). The virus has spread to 216 nations, regions, and territories around the world. There were around 510306 confirmed cases and 333401 deaths by May 2020. Patients with cardiovascular diseases and other co-morbidities were at a high risk of SARS-CoV-2 infection that ultimately resulted in the death of the patient. Objective: This review highlights the impact of COVID-19 on cardiovascular diseases and other comorbidities. Methods: This review was completed using different sources of search sites like Google Scholar, Pub- Med, ScienceDirect, Scopus, etc. Result: The diseases associated with the cardiovascular system include myocarditis, heart failure, cardiac injury, and microangiopathy. The mechanisms that cause cardiovascular problems in COVID-19 are myocardial injury pathways, systemic inflammation, altered myocardial demand and supply ratios, plaque rupture, coronary thrombosis, adverse effects of various therapies, and electrolyte imbalances. Several studies provide an important clinical and molecular clue to cardiac involvement during COVID-19. The high cytokine concentrations may contribute to myocardial lesions and a poor disease prognosis. In an earlier study, autopsy reports of COVID-19 found the SARS-CoV-2 genome in myocardial tissues. This also demonstrates that cytokine-induced organ dysfunction contributes to the disease process. Conclusion: This review concludes that the impact of coronavirus on the cardiac system has shown a harmful effect, and patients with co-morbidities are likely to be more affected by COVID-19 infection.

Mechanisms of Coronary Artery Spasm.

Recent clinical trials have highlighted that percutaneous coronary intervention in patients with stable angina provides limited additional benefits on top of optimal medical therapy. This has led to much more attention being paid to coronary vasomotion abnormalities regardless of obstructive or non-obstructive arterial segments. Coronary vasomotion is regulated by multiple mechanisms that include the endothelium, vascular smooth muscle cells (VSMCs), myocardial metabolic demand, autonomic nervous system and inflammation. Over the years, several animal models have been developed to explore the central mechanism of coronary artery spasm. This review summarises the landmark studies on the mechanisms of coronary vasospasm demonstrating the central role of Rho-kinase as a molecular switch of VSMC hypercontraction and the important role of coronary adventitial inflammation for Rho-kinase upregulation in VSMCs.

0008 The endogenous circadian system provides for enhanced coronary microvascular function in the morning

Abstract Introduction Major adverse cardiovascular events occur most commonly in the morning compared to other times of the day or night. Evaluation of coronary microvascular reserve perfusion can be used to reflect the anatomic and functional status of the coronary vascular system, both of which contribute to major adverse cardiovascular events. Prior work suggests that coronary microvascular function is attenuated in the morning, but whether the circadian system contributes to this attenuation is unknown. Methods To determine if the circadian system drives the morning attenuation in coronary microvascular function, we studied 13 healthy participants (8 females, 5 males; 42+/-13 years [mean+/-SD]) in a 5-day forced desynchrony protocol in dim light, where all behaviors and measurements were distributed across the 24-hour cycle. Coronary microvascular function was evaluated by vasodilator myocardial contrast echocardiography, sequentially 16 hours apart, corresponding to each participant’s morning, evening and night. We analyzed time-intensity data to calculate microvascular flux rate (beta) at rest and during hyperemia for each measurement. Circadian phases were calculated based on individual dim-light melatonin onsets. We grouped data into three ~8-hour circadian bins corresponding to each participant’s morning, evening and night. Mixed model analyses were used to determine if there were significant differences between data collected in the circadian morning compared to the other times while controlling for the measurement schedule and between-subject variability. Results There were no significant time-dependent differences in echocardiographic indices of ventricular function, including stroke volume, cardiac output, or myocardial work. Contrary to our hypothesis, hyperemic perfusion was lowest in the evening rather than the morning (2.49 /s vs. 2.82 /s, p=0.042) but not different between morning and night (also 2.82 /s, p=0.96). Conclusion In healthy people, there is no circadian-system-driven morning attenuation in coronary microvascular function: indeed, the circadian system facilitates coronary vascular flow in the morning, possibly to accommodate the anticipated behaviorally driven increases in myocardial demand after awakening. Support (if any) NIH KL2TR002370, R01HL163232, R35HL155681, R01HL140577, R01HL130046, R01HL078610, R01HL156948, K01HL146992, K01HL151745, ULTR00128, Sleep Research Society Foundation, Oregon Institute of Occupational Health Sciences.

Myocardial infarction and viral triggers: what do we know by now?

Myocardial infarction (MI) is an acute clinical manifestation ischaemic heart disease, which is the leading cause of death worldwide. Infections also have an important burden worldwide, with lower respiratory infections being the worldwide leading cause of death due to communicable diseases. The relationship of MI with viral respiratory infections (including influenza and SARS-CoV-2) as a trigger has been well documented with significant associations. These infections can lead to Type 1 MI, where inflammation and vascular dysfunction, as well as the increased prothrombotic environment lead to atherothrombosis. Type 2 MI may also occur due to an imbalance of oxygen/blood supply and myocardial demand (hypoxaemia, fever, and tachycardia). The data from randomized controlled trials showing a potential benefit of influenza vaccination in coronary artery disease patients should not be ignored. This can be considered a further argument for the association of viral infections (influenza in particular) and MI.

150 ECHO-DERIVED LEFT VENTRICULAR MECHANO-ENERGETIC EFFICACY CHARACTERIZES HYPERTENSIVE PATIENTS WITH IMPAIRED PET-DERIVED MYOCARDIAL BLOOD FLOW

Abstract Background Chronic left ventricular (LV) pressure overload determines both morphological and functional alterations in the heart and in the vascular system with occurrence of LV hypertrophy, coronary rarefaction and metabolic impairment, predisposing to heart failure. We aim at investigating early cardiac involvement in hypertensive disease by both Positron emission tomography (PET) and echo assessment and possible associations between alterations of PET-derived myocardial blood flow (MBF) and echocardiographic parameters of LV performance including mechano-energetic efficiency indexed for myocardial mass (MEEi), in a population of symptomatic hypertensive patients without flow-limiting epicardial coronary artery disease (CAD). Methods The study population included 78 symptomatic hypertensive patients without flow-limiting epicardial CAD. All patients underwent standard echocardiographic assessment, including evaluation of LV MEEi, and PET assessment with evaluation of MBF and MBF/mass ratio at rest and after stress and myocardial flow reserve (MFR). Results The study population included 67% males, 55% with dyslipidaemia, 42% with smoking habits and 21% obese. Prevalence of LV hypertrophy was of 43%. Among parameters of LV systolic performance, hyperaemic MBF/mass ratio resulted significantly correlated with LV MEEi (r=0.54, p<0.0001), midwall fractional shortening (r=0.38, p=0.001) but not with LVEF (r=0.10, p=0.47). Similarly, resting MBF/mass ratio resulted to have statistically significant correlations with LV MEEi (r=0.51, p<0.0001), midwall fractional shortening (r=0.29, p=0.01) but not with LVEF (r=0.11, p=0.39). LV MEEi reached the highest correlation coefficient with both resting and stress MBF/mass ratio. On the other hand, the correlation between MEEi and MFR did not reach statistical significance (r=0.11, p=0.33). In a multiple linear regression analysis, after adjusting for sex, systolic blood pressure, prevalence of LV hypertrophy and therapy with diuretics, the association between LV MEEi and hyperaemic MBF/mass ratio remained significant (beta coefficient =0.40, p=0.007). In a subsequent multivariate model, adjusting for the same confounders, by replacing hyperaemic MBF/mass ratio with resting MBF/mass ratio, LV MEEi and resting MBF/mass ratio continued to be significantly associated (beta coefficient =0.32, p=0.015). Conclusions In a population of hypertensive patients without flow-limiting epicardial CAD, an early myocardial impairment possibly related to coronary rarefaction and inadequate angiogenesis contributing to the altered myocardial metabolic demand and efficacy is detectable by both PET and echo-derived LV MEEi. Indeed, an independent association between LV MEEi and both MBF/mass ratio at rest and after stress exists, LV MEEi having the advantage over PET of being easily derived from standard echocardiography and not needing radiation exposure.

Mechanism of exercise intolerance in heart diseases predicted by a computer model of myocardial demand‐supply feedback system

Background and objectiveThe myocardial demand-supply feedback system plays an important role in augmenting blood supply in response to exercise-induced increased myocardial demand. During this feedback process, the myocardium and coronary blood flow interact bidirectionally at many different levels. MethodsTo investigate these interactions, a novel computational framework that considers the closed myocardial demand-supply feedback system was developed. In the framework coupling the systemic circulation of the left ventricle and coronary perfusion with regulation, myocardial work affects coronary perfusion via flow regulation mechanisms (e.g., metabolic regulation) and myocardial-vessel interactions, whereas coronary perfusion affects myocardial contractility in a closed feedback system. The framework was calibrated based on the measurements from healthy subjects under graded exercise conditions, and then was applied to simulate the effects of graded exercise on myocardial demand-supply under different physiological and pathological conditions. ResultsWe found that the framework can recapitulate key features found during exercise in clinical and animal studies. We showed that myocardial blood flow is increased but maximum hyperemia is reduced during exercise, which led to a reduction in coronary flow reserve. For coronary stenosis and myocardial inefficiency, the model predicts that an increase in heart rate is necessary to maintain the baseline cardiac output. Correspondingly, the resting coronary flow reserve is exhausted and the range of heart rate before exhaustion of coronary flow reserve is reduced. In the presence of metabolic regulation dysfunction, the model predicts that the metabolic vasodilator signal is higher at rest, saturates faster during exercise, and as a result, causes quicker exhaustion of coronary flow reserve. ConclusionsModel predictions showed that the coronary flow reserve deteriorates faster during graded exercise, which in turn, suggests a decrease in exercise tolerance for patients with stenosis, myocardial inefficiency and metabolic flow regulation dysfunction. The findings in this study may have clinical implications in diagnosing cardiovascular diseases.

Determinants of improvement of left ventricular mechano-energetic efficiency in hypertensive patients.

BackgroundArterial hypertension, especially when coexisting with other cardiovascular risk factors, could determine an imbalance between myocardial energetic demand and altered efficiency, leading to an early left ventricular (LV) systolic dysfunction, even in terms of echo-derived mechano-energetic efficiency indexed for myocardial mass (MEEi). We aim to analyse an improvement in LV MEEi, if any, in a population of hypertensive patients with a long-term follow-up and to identify clinical, metabolic and therapeutic determinants of LV MEEi amelioration.Materials and methodsIn total, 7,052 hypertensive patients, followed-up for 5.3 ± 4.5 years, enrolled in the Campania Salute Network, underwent echocardiographic and clinical evaluation. LV MEEi was obtained as the ratio between stroke volume and heart rate and normalized per grams of LV mass and ΔMEEi was calculated as difference between follow-up and baseline MEEi. Patients in the highest ΔMEEi quartile (≥0.0454 mL/s/g) (group 1) were compared to the merged first, second and third quartiles (<0.0454 mL/s/g) (group 2). METS-IR (Metabolic Score for Insulin Resistance), an established index of insulin sensitivity, was also derived.ResultsPatients with MEEi improvement experienced a lower rate of major cardiovascular events (p = 0.02). After excluding patients experiencing cardiovascular events, patients in group 1 were younger (p < 0.0001), less often diabetic (p = 0.001) and obese (p = 0.035). Group 1 experienced more frequently LV mass index reduction, lower occurrence of LV ejection fraction reduction, and had a better metabolic control in terms of mean METS-IR during the follow-up (all p < 0.0001). Beta-blockers were more often used in group 1 (p < 0.0001) than group 2. A logistic regression analysis showed that younger age, lower mean METS-IR values, more frequent LV mass index reduction and therapy with beta-blockers were significantly associated with LV MEEi improvement, independently of presence of diabetes and obesity.ConclusionMetabolic control and therapy with beta-blockers could act in a synergic way, determining an improvement in LV MEEi in hypertensive patients over time, possibly confining cardiac damage and hampering progression toward heart failure.

Numerical Analysis on Effect of Coronary Supply-Demand Equilibrium on Varying Coronary Blockage and Stress Conditions.

In this paper, we present a computational fluid dynamic (CFD) analysis to capture the effect of physical stress and stenosis severity in coronary arteries leading to changes in coronary supply demand oxygen equilibrium. We propose a coupled Od-3d coronary vessel model to predict the variation in flow dynamics of coronary as well as arterial system, modeled using an in-silico model replicating cardiovascular hemodynamics. CFD simulation were solved using subject specific CT scan for coronary and arterial flow and pressure along with metrics related to arterial wall shear stress. Simulations were performed for three heart rates (75, 90 and 120 bpm) and four stenosis states representing different stages of Coronary artery disease (CAD) namely healthy, 50%, 75%, 90% blockage in left anterior descending artery (LAD). Myocardial oxygen supply demand equilibrium were calculated for each cases using hemodynamic surrogate markers naming Diastolic pressure time index for supply and Tension time index for demand. The proposed 0d-3d coupled hemodynamic model of the coronary vessel bed along with supply-demand equilibrium estimated for different stress level and stenosis severity may provide useful insights on the dynamics of CAD manifestation and predict vulnerable regions in coronary bed for early screening and interventions.

VALIDATION OF A NONINVASIVE METHOD TO ESTIMATE SUBENDOCARDIAL OXYGEN SUPPLY AND DEMAND BALANCE

Objective: Evaluation of balance between subendocardial oxygen supply and demand is useful in order to assess the risk of myocardial ischemia. The subendocardial viability ratio (SEVR, also known as Buckberg index) evaluated by invasive recordings of left ventricular and aortic pressure curves represents a valid method to estimate the degree of myocardial perfusion relative to left ventricular workload. However, routine clinical use of this parameter requires a noninvasive estimation and the demonstration of its reliability. Design and method: Arterial applanation tonometry allows a noninvasive estimation of SEVR as the ratio of the areas directly beneath the central aortic pressure curves obtained during diastole (myocardial oxygen supply) and during systole (myocardial oxygen demand). However, this traditional method does not account for the intraventricular diastolic pressure and proper allocation to systole and diastole of left ventricular isometric contraction and relaxation, respectively, resulting in an overestimation of the SEVR values. These issues are considered in a novel method for SEVR assessment tested in this study. SEVR values were estimated with carotid tonometry by traditional and new method and compared with those evaluated invasively in 51 undergoing an cardiac catheterization for coronary angiography. Results: The traditional method provided significantly higher SEVR values than the reference invasive SEVR: average of differences ± SD = 44 ± 11%. The noninvasive new method showed a much better agreement with the invasive determination of SEVR: average of differences ± SD = 0 ± 8%. The new method for SEVR estimation showed a good repeatability between consecutive assessments (coefficient of variation 7.8%). Conclusions: A noninvasive estimation of SEVR by carotid applanation tonometry is feasible. All the main factors determining myocardial supply and demand flow should be considered in order to provide a valid estimate, in particular intraventricular diastolic pressure, left ventricular isometric contraction and relaxation.

REDUCTION OF HEART RATE VIA P2X4 RECEPTOR ACTIVATION AS A PROMISING TREATMENT STRATEGY IN PULMONARY ARTERIAL HYPERTENSION

Objective: Mounting evidence suggest that the ATP-sensitive ionotropic P2X4 receptor (P2X4R) improves cardiac performance and optimizes myocardial energy demand by reducing chronotropy. Here, we set to investigate whether the digitalis-like effect of the P2X4R in the sinus node was preserved in rats with right heart failure due to pulmonary arterial hypertension (PAH). Design and method: Male Wistar rats received a single subcutaneous injection of either monocrotaline (MCT; PAH group) or vehicle (CTRL group). Right heart failure associated to PAH normally occurs in Wistar rats 21 to 25 days after MCT administration. Myographic recordings were performed in spontaneously beating atria (chronotropic effect) isolated from both animal groups. Results: Baseline spontaneous atrial rate was 250 ± 5 (n = 26) bpm in CTRL and 237 ± 7 bpm (n = 23) in PAH group (p &gt; 0.05). ATP (0.01–1 mM) concentration-dependently reduced the spontaneous atrial rate of both animal groups. The negative chronotropic effect of ATP (100 M) was smaller in PAH rats (-9 ± 2%; n = 14 vs. -22 ± 4%; n = 25, p &lt; 0.05), but this divergence was attenuated upon increasing the concentration of ATP to 1 mM (CTRL: -54 ± 5%; n = 15 vs. MCT: -50 ± 7%; n = 8; p &gt; 0.05). The P2X4R antagonist, 5-BDBD (10 M), attenuated the negative chronotropic action of ATP (100 M) in CTRL (from -19 ± 5% to -13 ± 3%; n = 5, p &gt; 0.05) and PAH (from -8 ± 3% to 1 ± 8%; n = 4, p &gt; 0.05) rats. The positive allosteric modulator of P2X4R, ivermectin (30 M), potentiated the negative chronotropic effect of ATP (100 M) in CTRL (from -31 ± 5% to -56 ± 14%; n = 5, p &gt; 0.05) and PAH (from -12 ± 6% to -24 ± 9%; n = 4, p &lt; 0.05). The non-selective P2XR agonist, CTP (1 mM), which contrary to ATP does not breakdown into adenosine, also decreased atrial chronotropy in CTRL (-24.31 ± 6.73%; n = 6) and PAH (-11.82 ± 1.98%; n = 6) rats. Conclusions: Data suggest that the negative chronotropic effect of P2X4R activation is preserved in atria of rats with heart failure associated to PAH, thus strengthening the hypothesis that heart rate reductions using this ATP-sensitive receptor may increase cardiac performance in patients with PAH-induced heart failure.

61-Year-Old Man With Nausea and Vomiting

61-Year-Old Man With Nausea and Vomiting

Transmural Distribution of Coronary Perfusion and Myocardial Work Density Due to Alterations in Ventricular Loading, Geometry and Contractility.

Myocardial supply changes to accommodate the variation of myocardial demand across the heart wall to maintain normal cardiac function. A computational framework that couples the systemic circulation of a left ventricular (LV) finite element model and coronary perfusion in a closed loop is developed to investigate the transmural distribution of the myocardial demand (work density) and supply (perfusion) ratio. Calibrated and validated against measurements of LV mechanics and coronary perfusion, the model is applied to investigate changes in the transmural distribution of passive coronary perfusion, myocardial work density, and their ratio in response to changes in LV contractility, preload, afterload, wall thickness, and cavity volume. The model predicts the following: (1) Total passive coronary flow varies from a minimum value at the endocardium to a maximum value at the epicardium transmurally that is consistent with the transmural distribution of IMP; (2) Total passive coronary flow at different transmural locations is increased with an increase in either contractility, afterload, or preload of the LV, whereas is reduced with an increase in wall thickness or cavity volume; (3) Myocardial work density at different transmural locations is increased transmurally with an increase in either contractility, afterload, preload or cavity volume of the LV, but is reduced with an increase in wall thickness; (4) Myocardial work density-perfusion mismatch ratio at different transmural locations is increased with an increase in contractility, preload, wall thickness or cavity volume of the LV, and the ratio is higher at the endocardium than the epicardium. These results suggest that an increase in either contractility, preload, wall thickness, or cavity volume of the LV can increase the vulnerability of the subendocardial region to ischemia.