A simulation study on the antiarrhythmic mechanisms of established agents in myocardial ischemia and infarction.

Patients with myocardial ischemia and infarction are at increased risk of arrhythmias, which in turn, can exacerbate the overall risk of mortality. Despite the observed reduction in recurrent arrhythmias through antiarrhythmic drug therapy, the precise mechanisms underlying their effectiveness in treating ischemic heart disease remain unclear. Moreover, there is a lack of specialized drugs designed explicitly for the treatment of myocardial ischemic arrhythmia. This study employs an electrophysiological simulation approach to investigate the potential antiarrhythmic effects and underlying mechanisms of various pharmacological agents in the context of ischemia and myocardial infarction (MI). Based on physiological experimental data, computational models are developed to simulate the effects of a series of pharmacological agents (amiodarone, telmisartan, E-4031, chromanol 293B, and glibenclamide) on cellular electrophysiology and utilized to further evaluate their antiarrhythmic effectiveness during ischemia. On 2D and 3D tissues with multiple pathological conditions, the simulation results indicate that the antiarrhythmic effect of glibenclamide is primarily attributed to the suppression of efflux of potassium ion to facilitate the restitution of [K+]o, as opposed to recovery of IKATP during myocardial ischemia. This discovery implies that, during acute cardiac ischemia, pro-arrhythmogenic alterations in cardiac tissue's excitability and conduction properties are more significantly influenced by electrophysiological changes in the depolarization rate, as opposed to variations in the action potential duration (APD). These findings offer specific insights into potentially effective targets for investigating ischemic arrhythmias, providing significant guidance for clinical interventions in acute coronary syndrome.

Cardiac shockwave therapy in addition to coronary bypass surgery improves myocardial function in ischaemic heart failure: the CAST-HF trial.

BACKGROUND AND AIMS: In chronic ischaemic heart failure, revascularisation strategies control symptoms but are less effective in improving left ventricular ejection fraction (LVEF). The aim of this trial is to investigate the safety of cardiac shockwave therapy (SWT) as a novel treatment option and its efficacy in increasing cardiac function by inducing angiogenesis and regeneration in hibernating myocardium. METHODS: In this single-blind, parallel-group, sham-controlled trial (cardiac shockwave therapy for ischemic heart failure, CAST-HF; NCT03859466) patients with LVEF ≤40% requiring surgical revascularisation were enrolled. Patients were randomly assigned to undergo direct cardiac SWT or sham treatment in addition to coronary bypass surgery. The primary efficacy endpoint was the improvement in LVEF measured by cardiac magnetic resonance imaging from baseline to 360 days. RESULTS: Overall, 63 patients were randomized, out of which 30 patients of the SWT group and 28 patients of the Sham group attained 1-year follow-up of the primary endpoint. Greater improvement in LVEF was observed in the SWT group (Δ from baseline to 360 days: SWT 11.3%, SD 8.8; Sham 6.3%, SD 7.4, P = .0146). Secondary endpoints included the 6-minute walking test, where patients randomized in the SWT group showed a greater Δ from baseline to 360 days (127.5 m, SD 110.6) than patients in the Sham group (43.6 m, SD 172.1) (P = .028) and Minnesota Living with Heart Failure Questionnaire score on day 360, which was 11.0 points (SD 19.1) for the SWT group and 17.3 points (SD 15.1) for the Sham group (P = .15). Two patients in the treatment group died for non-device-related reasons. CONCLUSIONS: In conclusion, the CAST-HF trial indicates that direct cardiac SWT, in addition to coronary bypass surgery improves LVEF and physical capacity in patients with ischaemic heart failure.

Bone marrow cells contribute to seven different endothelial cell populations in the heart.

Understanding the mechanisms underlying vascular regeneration in the heart is crucial for developing novel therapeutic strategies for myocardial ischemia. This study investigates the contribution of bone marrow-derived cells to endothelial cell populations in the heart, and their role in cardiac function and coronary circulation following repetitive ischemia (RI). Chimeric rats were created by transplanting BM cells from GFP female rats into irradiated male recipients. After engraftment chimeras were subjected to RI for 17 days. Vascular growth was assessed from recovery of cardiac function and increases in myocardial blood flow during LAD occlusion. After sorting GFP+ BM cells from heart and bone of Control and RI rats, single-cell RNA sequencing was implemented to determine the fate of BM cells. Our in vivo RI model demonstrated an improvement in cardiac function and myocardial blood flow after 17 days of RI with increased capillary density in the rats subjected to RI compared to Controls. Single-cell RNA sequencing of bone marrow cells isolated from rats' hearts identified distinct endothelial cell (EC) subpopulations. These ECs exhibited heterogeneous gene expression profiles and were enriched for markers of capillary, artery, lymphatic, venous, and immune ECs. Furthermore, BM-derived ECs in the RI group showed an angiogenic profile, characterized by upregulated genes associated with blood vessel development and angiogenesis. This study elucidates the heterogeneity of bone marrow-derived endothelial cells in the heart and their response to repetitive ischemia, laying the groundwork for targeting specific subpopulations for therapeutic angiogenesis in myocardial ischemia.

Gasotransmitters and noble gases in cardioprotection: unraveling molecular pathways for future therapeutic strategies.

Despite recent progress, ischemic heart disease poses a persistent global challenge, driving significant morbidity and mortality. The pursuit of therapeutic solutions has led to the emergence of strategies such as ischemic preconditioning, postconditioning, and remote conditioning to shield the heart from myocardial ischemia/reperfusion injury (MIRI). These ischemic conditioning approaches, applied before, after, or at a distance from the affected organ, inspire future therapeutic strategies, including pharmacological conditioning. Gasotransmitters, comprising nitric oxide, hydrogen sulfide, sulfur dioxide, and carbon monoxide, play pivotal roles in physiological and pathological processes, exhibiting shared features such as smooth muscle relaxation, antiapoptotic effects, and anti-inflammatory properties. Despite potential risks at high concentrations, physiological levels of gasotransmitters induce vasorelaxation and promote cardioprotective effects. Noble gases, notably argon, helium, and xenon, exhibit organ-protective properties by reducing cell death, minimizing infarct size, and enhancing functional recovery in post-ischemic organs. The protective role of noble gases appears to hinge on their modulation of molecular pathways governing cell survival, leading to both pro- and antiapoptotic effects. Among noble gases, helium and xenon emerge as particularly promising in the field of cardioprotection. This overview synthesizes our current understanding of the roles played by gasotransmitters and noble gases in the context of MIRI and cardioprotection. In addition, we underscore potential future developments involving the utilization of noble gases and gasotransmitter donor molecules in advancing cardioprotective strategies.

Beating the heart failure odds: long-term survival after myocardial ischemia in juvenile rainbow trout.

Salmonid fish include some of the most valued cultured fish species worldwide. Unlike most other fish, the hearts of salmonids, including Atlantic salmon and rainbow trout, have a well-developed coronary circulation. Consequently, their hearts' reliance on oxygenation through coronary arteries leaves them prone to coronary lesions, believed to precipitate myocardial ischemia. Here, we mimicked such coronary lesions by subjecting groups of juvenile rainbow trout to coronary ligation, assessing histomorphological myocardial changes associated with ischemia and scarring in the context of cardiac arrhythmias using electrocardiography (ECG). Notable ECG changes resembling myocardial ischemia-like ECG in humans, such as atrioventricular blocks and abnormal ventricular depolarization (prolonged and fragmented QRS complex), as well as repolarization (long QT interval) patterns, were observed during the acute phase of myocardial ischemia. A remarkable 100% survival rate was observed among juvenile trout subjected to coronary ligation after 24 wk. Recovery from coronary ligation occurred through adaptive ventricular remodeling, coupled with a fast cardiac revascularization response. These findings carry significant implications for understanding the mechanisms governing cardiac health in salmonid fish, a family particularly susceptible to cardiac diseases. Furthermore, our results provide valuable insights into comparative studies on the evolution, pathophysiology, and ontogeny of vertebrate cardiac repair and restoration.NEW & NOTEWORTHY Juvenile rainbow trout exhibit a remarkable capacity to recover from cardiac injury caused by myocardial ischemia. Recovery from cardiac damage occurs through adaptive ventricular remodeling, coupled with a rapid cardiac revascularization response. These findings carry significant implications for understanding the mechanisms governing cardiac health within salmonid fishes, which are particularly susceptible to cardiac diseases.

Ventricular tachycardia ablation with pentaspline pulsed field technology in two patients with ischemic cardiomyopathy.

INTRODUCTION: Due to its unique features, pulsed field ablation (PFA) could potentially overcome some limitations of current radiofrequency (RF) ventricular tachycardia (VT) ablation. However, data on the use of PFA in this setting are currently scarce. METHODS: Two patients with ischemic cardiomyopathy and previously failed RF VT ablations were treated with PFA. RESULTS: A total of 18 bipolar applications (case1) and seven bipolar applications (case2) were delivered to the infero-lateral and infero-septal areas (case1) and to the apical lateral left ventricular (LV) wall (case2), placing the catheter adjacent to the LV wall in the flower configuration. A rapid cessation of VT and restoration of sinus rhythm were observed during PFA delivery in both cases. Further applications were delivered to achieve complete elimination of late potentials. In case 1, during the in-hospital stay, ECG monitoring did not show VT recurrences. Six-month follow-up was uneventful, with no VT recurrences at ICD interrogation. In case 2, due to postdischarge VT recurrences, a second RF procedure was scheduled 1 month later. The voltage map performed in sinus rhythm showed a low-voltage zone located at the anterolateral wall, near the previous ablation site. Numerous late potentials were recorded. At the 6-month follow-up, no further VT recurrences were documented after RF redo ablation. CONCLUSION: While the speed of application and potential transmural effect can facilitate the ablation of large diseased endocardial areas, early loss of contact due to difficult pentaspline catheter manipulation in the LV could lead to insufficient contact force and, consequently, inadequate energy penetration.

Mitochondrial network remodeling of the diabetic heart: implications to ischemia related cardiac dysfunction.

Mitochondria play a central role in cellular energy metabolism, and their dysfunction is increasingly recognized as a critical factor in the pathogenesis of diabetes-related cardiac pathophysiology, including vulnerability to ischemic events that culminate in myocardial infarction on the one hand and ventricular arrhythmias on the other. In diabetes, hyperglycemia and altered metabolic substrates lead to excessive production of reactive oxygen species (ROS) by mitochondria, initiating a cascade of oxidative stress that damages mitochondrial DNA, proteins, and lipids. This mitochondrial injury compromises the efficiency of oxidative phosphorylation, leading to impaired ATP production. The resulting energy deficit and oxidative damage contribute to functional abnormalities in cardiac cells, placing the heart at an increased risk of electromechanical dysfunction and irreversible cell death in response to ischemic insults. While cardiac mitochondria are often considered to be relatively autonomous entities in their capacity to produce energy and ROS, their highly dynamic nature within an elaborate network of closely-coupled organelles that occupies 30-40% of the cardiomyocyte volume is fundamental to their ability to exert intricate regulation over global cardiac function. In this article, we review evidence linking the dynamic properties of the mitochondrial network to overall cardiac function and its response to injury. We then highlight select studies linking mitochondrial ultrastructural alterations driven by changes in mitochondrial fission, fusion and mitophagy in promoting cardiac ischemic injury to the diabetic heart.

Impact on cardiovascular outcome of coronary revascularization-induced changes in ischemic perfusion defect and myocardial flow reserve.

PURPOSE: We evaluated the impact on cardiovascular outcome of coronary revascularization-induced changes in ischemic total perfusion defect (ITPD) and myocardial flow reserve (MFR) as assessed by 82Rb positron emission tomography (PET)/computed tomography (CT) imaging. METHODS: The study included 102 patients referred to 82Rb PET/CT myocardial perfusion imaging before and after coronary revascularization. All patients were followed for the occurrence of cardiovascular events (cardiac death, nonfatal myocardial infarction, repeated revascularization, and heart failure) after the second imaging study. RESULTS: During a median follow-up of 20 months, 21 events occurred. The clinical characteristics were comparable between patients with and without events. In the overall study population, after revascularization, there was a significant reduction (P < 0.001) of ITPD, while hyperemic myocardial blood flow (MBF) (P < 0.01) and MFR (P < 0.05) significantly improved. Event rate was higher in patients with ITPD (P < 0.005) or MFR (P < 0.001) worsening compared to those with unchanged or improved ITPD or MFR. At Cox univariable analysis, ITPD and MFR worsening resulted in predictors of events (both P < 0.05). Patients with worsening of both ITPD and MFR had the worst event-free survival (log-rank 32.9, P for trend < 0.001). CONCLUSIONS: In patients with stable CAD, worsening of ITPD and MFR after revascularization procedures is associated with higher risk of cardiovascular events. Follow-up MPI with 82Rb PET/CT may improve risk stratification in patients submitted to coronary revascularization.

Diastolic function assessment with four-dimensional flow cardiovascular magnetic resonance using automatic deep learning E/A ratio analysis.

BACKGROUND: Diastolic left ventricular (LV) dysfunction is a powerful contributor to the symptoms and prognosis of patients with heart failure. In patients with depressed LV systolic function, the E/A ratio, the ratio between the peak early (E) and the peak late (A) transmitral flow velocity, is the first step to defining the grade of diastolic dysfunction. Doppler echocardiography (echo) is the preferred imaging technique for diastolic function assessment, while cardiovascular magnetic resonance (CMR) is less established as a method. Previous four-dimensional (4D) Flow-based studies have looked at the E/A ratio proximal to the mitral valve, requiring manual interaction. In this study, we compare an automated, deep learning-based and two semi-automated approaches for 4D Flow CMR-based E/A ratio assessment to conventional, gold-standard echo-based methods. METHODS: Ninety-seven subjects with chronic ischemic heart disease underwent a cardiac echo followed by CMR investigation. 4D Flow-based E/A ratio values were computed using three different approaches; two semi-automated, assessing the E/A ratio by measuring the inflow velocity (MVvel) and the inflow volume (MVflow) at the mitral valve plane, and one fully automated, creating a full LV segmentation using a deep learning-based method with which the E/A ratio could be assessed without constraint to the mitral plane (LVvel). RESULTS: MVvel, MVflow, and LVvel E/A ratios were strongly associated with echocardiographically derived E/A ratio (R2 = 0.60, 0.58, 0.72). LVvel peak E and A showed moderate association to Echo peak E and A, while MVvel values were weakly associated. MVvel and MVflow EA ratios were very strongly associated with LVvel (R2 = 0.84, 0.86). MVvel peak E was moderately associated with LVvel, while peak A showed a strong association (R2 = 0.26, 0.57). CONCLUSION: Peak E, peak A, and E/A ratio are integral to the assessment of diastolic dysfunction and may expand the utility of CMR studies in patients with cardiovascular disease. While underestimation of absolute peak E and A velocities was noted, the E/A ratio measured with all three 4D Flow methods was strongly associated with the gold standard Doppler echocardiography. The automatic, deep learning-based method performed best, with the most favorable runtime of ∼40 seconds. As both semi-automatic methods associated very strongly to LVvel, they could be employed as an alternative for estimation of E/A ratio.

Diagnostic confidence with quantitative cardiovascular magnetic resonance perfusion mapping increases with increased coverage of the left ventricle.

BACKGROUND: Quantitative cardiovascular magnetic resonance (CMR) first pass perfusion maps are conventionally acquired with 3 short-axis (SAX) views (basal, mid, and apical) in every heartbeat (3SAX/1RR). Thus, a significant part of the left ventricle (LV) myocardium, including the apex, is not covered. The aims of this study were 1) to investigate if perfusion maps acquired with 3 short-axis views sampled every other RR-interval (2RR) yield comparable quantitative measures of myocardial perfusion (MP) as 1RR and 2) to assess if acquiring 3 additional perfusion views (i.e., total of 6) every other RR-interval (2RR) increases diagnostic confidence. METHODS: In 287 patients with suspected ischemic heart disease stress and rest MP were performed on clinical indication on a 1.5T MR scanner. Eighty-three patients were examined by acquiring 3 short-axis perfusion maps with 1RR sampling (3SAX/1RR); for which also 2RR maps were reconstructed. Additionally, in 103 patients 3 short-axis and 3 long-axis (LAX; 2-, 3, and 4-chamber view) perfusion maps were acquired using 2RR sampling (3SAX + 3LAX/2RR) and in 101 patients 6 short-axis perfusion maps using 2RR sampling (6SAX/2RR) were acquired. The diagnostic confidence for ruling in or out stress-induced ischemia was scored according to a Likert scale (certain ischemia [2 points], probably ischemia [1 point], uncertain [0 points], probably no ischemia [1 point], certain no ischemia [2 points]). RESULTS: There was a strong correlation (R = 0.99) between 3SAX/1RR and 3SAX/2RR for global MP (mL/min/g). The diagnostic confidence score increased significantly when the number of perfusion views was increased from 3 to 6 (1.24 ± 0.68 vs 1.54 ± 0.64, p < 0.001 with similar increase for 3SAX+3LAX/2RR (1.29 ± 0.68 vs 1.55 ± 0.65, p < 0.001) and for 6SAX/2RR (1.19 ± 0.69 vs 1.53 ± 0.63, p < 0.001). CONCLUSION: Quantitative perfusion mapping with 2RR sampling of data yields comparable perfusion values as 1RR sampling, allowing for the acquisition of additional views within the same perfusion scan. The diagnostic confidence for stress-induced ischemia increases when adding 3 additional views, short- or long axes, to the conventional 3 short-axis views. Thus, future development and clinical implementation of quantitative CMR perfusion should aim at increasing the LV coverage from the current standard using 3 short-axis views.

Unrecognized myocardial scar by late-gadolinium-enhancement cardiovascular magnetic resonance: Insights from the population-based Hamburg City Health Study.

BACKGROUND: The presence of myocardial scar is associated with poor prognosis in several underlying diseases. Late-gadolinium-enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging reveals clinically silent "unrecognized myocardial scar" (UMS), but the etiology of UMS often remains unclear. This population-based CMR study evaluated prevalence, localization, patterns, and risk factors of UMS. METHODS: The study population consisted of 1064 consecutive Hamburg City Health Study participants without a history of coronary heart disease or myocarditis. UMS was assessed by standard-phase-sensitive-inversion-recovery LGE CMR. RESULTS: Median age was 66 [quartiles 59, 71] years and 37% (388/1064) were females. UMS was detected in 244 (23%) participants. Twenty-five participants (10%) had ischemic, and 217 participants (89%) had non-ischemic scar patterns, predominantly involving the basal inferolateral left-ventricular (LV) myocardium (75%). Two participants (1%) had coincident ischemic and non-ischemic scar. The presence of any UMS was independently associated with LV ejection fraction (odds ratios (OR) per standard deviation (SD) 0.77 (confidence interval (CI) 0.65-0.90), p = 0.002) and LV mass (OR per SD 1.54 (CI 1.31-1.82), p < 0.001). Ischemic UMS was independently associated with LV ejection fraction (OR per SD 0.58 (CI 0.39-0.86), p = 0.007), LV mass (OR per SD 1.74 (CI 1.25-2.45), p = 0.001), and diabetes (OR 4.91 (CI 1.66-13.03), p = 0.002). Non-ischemic UMS was only independently associated with LV mass (OR per SD 1.44 (CI 1.24-1.69), p < 0.001). CONCLUSION: UMS, in particular with a non-ischemic pattern, is frequent in individuals without known cardiac disease and predominantly involves the basal inferolateral LV myocardium. Presence of UMS is independently associated with a lower LVEF, a higher LV mass, and a history of diabetes.

Left ventricular shape index and eccentricity index with ECG-gated Nitrogen-13 ammonia PET/CT in patients with myocardial infarction, ischemia, and normal perfusion.

BACKGROUND: LV geometry with shape index (SI) and eccentricity index (EI) measured by myocardial perfusion positron emission tomography/computed tomography (PET/CT) may allow the evaluation of left ventricular (LV) adverse remodeling. This first study aims to explore the relationship of SI and EI values acquired by Nitrogen-13 ammonia PET/CT in patients with normal perfusion, ischemia, and myocardial infarction. And evaluate the correlations between the variables of LV geometry, and with the variables of LV function. METHODS AND RESULTS: One hundred and forty patients who underwent an electrocardiogram (ECG)-gated PET/CT were selected and classified into 4 groups according to ischemia or infarction burden (normal perfusion, mild ischemia, moderate-severe ischemia, and infarction). The variables were automatically retrieved using dedicated software (QPS/QGS; Cedars-Sinai, Los Angeles, CA, USA). On multicomparison analysis (one-way ANOVA and Dunnett's Test), subjects in the infarction group had significant higher values of SI end-diastolic rest (P < 0.001), and stress (P = 0.003), SI end-systolic rest (P = 0.002) and stress (P < 0.001) as well as statistically significant lower values of EI rest (P < 0.001) and stress (P < 0.001) when compared with all other groups. Regarding Pearson correlation, in the infarcted group all the variables of SI and EI were significantly correlated (P < 0.001) with strong correlation coefficients (>0.60). SI end-systolic correlated significantly with the variables of LV function independently of the group of patients (P < 0.05). CONCLUSIONS: Shape and eccentricity indices differ in patients with myocardial infarction as compared to patients with ischemia or normal perfusion. This encourage further research in their potential for detecting LV adverse remodeling.

Role of myocardial strain imaging in diagnosing inducible myocardial ischemia with treadmill contrast-enhanced stress echocardiography.

INTRODUCTION: The aim of this study is to analyze the diagnostic value of global longitudinal strain (GLS) in detecting inducible myocardial ischemia in patients with chest pain undergoing treadmill contrast-enhanced stress echocardiography (SE). METHODS: We retrospectively enrolled all patients who underwent invasive coronary angiography after treadmill contrast-enhanced SE. Rest and peak-stress myocardial GLS, segmental LS, and LS of 4-chamber (CH), 2-CH, and 3-CH views were reported. Luminal stenosis of more than 70% or fractional flow reserve (FFR) of < 0.8 was considered significant. RESULTS: In total 33 patients were included in the final analysis, among whom sixteen patients (48.4%) had significant coronary artery stenosis. Averaged GLS, 3-CH, and 4-CH LS were significantly lower in patients with critical coronary artery stenosis compared to those without significant stenosis (-17.1 ± 7.1 vs. -24.2 ± 7.2, p = 0.041), (-18.2 ± 8.9 vs. -24.6 ± 8.2, p = 0.045) and (-14.8 ± 6.2 vs. -22.8 ± 7.8, p = 0.009), respectively. Receiver operating characteristic (ROC) analysis of ischemic and non-ischemic segments demonstrated that a cut-off value of -20% of stress LS had 71% sensitivity and 60% specificity for ruling out inducible myocardial ischemia (Area under the curve was AUC = 0.72, P < 0.0001). CONCLUSION: Myocardial LS measured with treadmill contrast-enhanced stress echocardiography demonstrates potential value in identifying patients with inducible myocardial ischemia.

Myocardial ischemia caused by the synergistic effect of myocardial bridge and moderate stenosis: case report.

BACKGROUND: Clinical events such as angina pectoris, acute coronary syndrome, and sudden death caused by myocardial bridge (MB) have attracted increasing attention. It is still a challenge to diagnose whether MB can cause the symptoms of patients with MB. For most MB patients, medication remains the primary treatment. CASE PRESENTATION: This article reports a case of chest pain in a patient with MB in the middle segment of the left anterior descending artery (LADm) with moderate stenosis in the proximal segment (LADp). Through functional assessment, we found that neither MB nor fixed stenosis had sufficient effect on coronary blood flow to cause myocardial ischemia, but their synergistic effect resulted in myocardial ischemia. Finally, a stent was implanted in LADp and good clinical results were achieved. CONCLUSIONS: For symptomatic patients with MB combined with fixed stenosis, functional evaluation may be necessary, which has significant guiding significance for treatment strategy selection. For asymptomatic patients, early detection of myocardial ischemia may also improve the prognosis of patients.

Is ischemic stimulus involved for J wave augmentation during coronary angiography and intracoronary administration of normal saline?

BACKGROUND: J waves may be augmented by coronary angiography (CAG) or intracoronary drug administration but the underlying mechanism is unknown. PURPOSE: The effect of intracoronary normal saline (NS) on J waves were investigated. PATIENTS AND METHODS: After the standard CAG using iopamidol (IopamiroR Inj), NS was injected into the right coronary artery in 10 patients with and eight patients without J waves at the baseline. The 12-lead ECG was monitored, stored on a computer and retrieved later for measurement of the J wave amplitude before or during the coronary interventions. RESULTS: J waves in leads II, III and aVF at baseline increased significantly in each lead during the right CAG and NS injection into the right coronary artery. The J wave changes were similar between the two interventions and distinct similar alterations were observed in the QRS complex. We postulated that the ischemic myocardium that was induced during CAG or intracoronary NS administration slowed the conduction velocity of depolarization in the perfusion territory and delayed the timing of J waves to appear. Then, the delayed appearance of J waves would be less opposed by electromotive force from other areas resulting in augmentation. CONCLUSION: J wave augmentation was observed during CAG and intracoronary NS administration. As a mechanism of augmentation, we postulated that contrast media and NS induce myocardial ischemia and delay the timing of J waves to a point of less opposition by electromotive force from other areas. HIGHLIGHTS: J wave augmentation has been reported during intracoronary injection of contrast media or drugs. The present study confirmed that normal saline alone was able to augment J waves. Mechanistically, coronary interventions using anoxic solutions can cause regional myocardial ischemia and reduce the conduction velocity of depolarization. Then, delayed J waves are less opposed by the electromotive force from remote areas which leads to augmentation. When a drug is diluted in normal saline and given intracoronarily, changes in J waves can be due to normal saline. The pathophysiological and clinical significance of J waves augmented during coronary interventions need to be established.

Challenges and benefits of using the HeartDiet food frequency questionnaire in cardiac rehabilitation practice.

BACKGROUND AND AIMS: A heart-healthy diet is an important component of secondary prevention in ischemic heart disease. The Danish Health Authority recommends using the validated 19-item food frequency questionnaire HeartDiet in cardiac rehabilitation practice to assess patients' need for dietary interventions, and HeartDiet has been included in national electronic patient-reported outcome instruments for cardiac rehabilitation. This study aims to evaluate challenges and benefits of its use. The objectives are to: 1) describe HeartDiet responses of patients with ischemic heart disease and discuss HeartDiet's suitability as a screening tool, 2) discuss whether an abridged version should replace HeartDiet. METHODS AND RESULTS: A cross-sectional study using data from a national feasibility test. HeartDiet was sent electronically to 223 patients with ischemic heart disease prior to cardiac rehabilitation. Data were summarised with descriptive statistics, and Spearman's rank correlations, explorative factor analysis, and Cohen's kappa coefficient were used to derive and evaluate abridged versions. The response rate was 68 % (n = 151). Evaluated with HeartDiet, no respondents had a heart-healthy diet. There was substantial agreement between HeartDiet and an abridged 9-item version (kappa = 0.6926 for Fat Score, 0.6625 for FishFruitVegetable Score), but the abridged version omits information on milk products, wholegrain, nuts, and sugary snacks. CONCLUSION: With the predefined cut-offs, HeartDiet's suitability as a screening tool to assess needs for dietary interventions was limited, since no respondents were categorised as having a heart-healthy diet. An abridged version can replace HeartDiet, but the tool's educational potential will be compromised, since important items will be omitted.

Relationship between coronary microvascular dysfunction (CMD) and left ventricular diastolic function in patients with symptoms of myocardial ischemia with non-obstructive coronary artery disease (INOCA) by cardiovascular magnetic resonance feature-tracking.

AIM: To investigate whether there was an association between coronary microvascular dysfunction (CMD) and left ventricular (LV) diastolic function in patients with myocardial ischemia with non-obstructive coronary artery disease (INOCA). MATERIALS AND METHODS: Our study included 115 subjects with suspected myocardial ischemia that underwent stress perfusion cardiac magnetic resonance (CMR). They were divided into non-CMD and CMD two groups. CMR-derived volume-time curves and CMR-FT parameters were used to assess LV diastolic function using CVI42 software. The latter included global/regional LV peak longitudinal, circumferential, radial diastolic strain rate (LDSR, CDSR, RDSR). Logistic regression analysis was performed with CMR-FT strain parameters as independent variables and CMD as dependent variables, and the effect value was expressed as an odds ratio (OR). RESULTS: Of the 115 patients, we excluded data from 23 patients and 92 patients (56.5% male；52 ± 12 years) were finally included in the study. Of these, 19 patients were included in the non-CMD group (49 ± 11 years) and CMD group included 73patient (52 ± 12 years). The regional CDSR (P=0.019), and regional RDSR (P=0.006) were significantly lower in the CMD group than in non-CMD group. But, regional LDSR in CMD group was higher than non-CMD (P=0.003). In logistic regression analysis, regional LDSR (adjusted ß= 0.1, 95%CI 0.077, 0.349, p=0.002) and RDSR (adjusted ß= 0.1, 95 % CI 0.066, 0.356, p=0.004) were related to CMD. CONCLUSIONS: LV myocardial perfusion parameter MPRI was negatively correlated with LV diastolic function (CDSR) which needs to take into account the degree of diastolic dysfunction.

Formation of a border ischemic zone depends on plasma potassium concentration.

Extracellular potassium concentration might modify electrophysiological properties in the border zone of ischemic myocardium. We evaluated the depolarization and repolarization characteristics across the ischemic-normal border under [K+] variation. Sixty-four-lead epicardial mapping was performed in 26 rats ([K+] 2.3-6.4 mM) in a model of acute ischemia/reperfusion. The animals with [K+] < 4.7 mM (low-normal potassium) had an ischemic zone with ST-segment elevation and activation delay, a border zone with ST-segment elevation and no activation delay, and a normal zone without electrophysiological abnormalities. The animals with [K+] >4.7 mM (normal-high potassium) had only the ischemic and normal zones and no transitional area. Activation-repolarization intervals and local conduction velocities were inversely associated with [K+] in linear regression analysis with adjustment for the zone of myocardium. The reperfusion extrasystolic burden (ESB) was greater in the low-normal as compared to normal-high potassium animals. Ventricular tachycardia/fibrillation incidence did not differ between the groups. In patch-clamp experiments, hypoxia shortened action potential duration at 5.4 mM but not at 1.3 mM of [K+]. IK(ATP) current was lower at 1.3 mM than at 5.4 mM of [K+]. We conclude that the border zone formation in low-normal [K+] was associated with attenuation of IK(ATP) response to hypoxia and increased reperfusion ESB.

Percutaneous Coronary Intervention as a Non-Surgical Treatment for Ischemic Mitral Regurgitation in Patients with Multi-Vessel Coronary Artery Disease.

BACKGROUND Multi-vessel coronary artery disease (MVD) represents a severe type of coronary artery disease (CAD). Ischemic mitral regurgitation (IMR) is a common mechanical complication in patients with CAD. This study aimed to retrospectively investigate the efficacy of percutaneous coronary intervention (PCI) on moderate/severe IMR in patients with MVD. MATERIAL AND METHODS Clinical data were collected from 15 patients who underwent successful treatment for MVD combined with moderate/severe IMR through the PCI procedure and achieved complete revascularization between January 2014 and December 2022. Cardiac structural and functional parameters were assessed through echocardiographic evaluations. Color flow recordings of MR jets were obtained through an enlarged view of the 4-chamber cut, and the diagnosis of MR was categorized into mild (<4 cm²), moderate (4-8 cm²), and severe (>8 cm²), based on the MR area. RESULTS The common features of the selected cases were advanced age, low body weight, and renal insufficiency. Cardiac echocardiography revealed an augmentation in the left atrial anteroposterior diameter and left ventricular internal diameter at end-systole after PCI, while the left ventricle internal diameter in diastole, left ventricular ejection fraction, and left ventricular fractional shortening were comparable to preoperative values. All patients had moderate/severe MR preoperatively, and MR improved at 1 month (2.73±0.69) and 12 months (2.26±0.58) after PCI. CONCLUSIONS In cases of MVD accompanied by moderate/severe IMR, undergoing PCI can spare certain elderly patients with low body weight and renal insufficiency from high-risk surgery, alleviating the severity of MR without undergoing mitral valve intervention.

GRK5 is a regulator of fibroblast activation and cardiac fibrosis.

Pathological remodeling of the heart is a hallmark of chronic heart failure (HF) and these structural changes further perpetuate the disease. Cardiac fibroblasts are the critical cell type that is responsible for maintaining the structural integrity of the heart. Stress conditions, such as a myocardial infarction (MI), can activate quiescent fibroblasts into synthetic and contractile myofibroblasts. G protein-coupled receptor kinase 5 (GRK5) is an important mediator of cardiovascular homeostasis through dampening of GPCR signaling, and is expressed in the heart and up-regulated in human HF. Of note, GRK5 has been demonstrated to translocate to the nucleus in cardiomyocytes in a calcium-calmodulin (Ca2+-CAM)-dependent manner, promoting hypertrophic gene transcription through activation of nuclear factor of activated T cells (NFAT). Interestingly, NFAT is also involved in fibroblast activation. GRK5 is highly expressed and active in cardiac fibroblasts; however, its pathophysiological role in these crucial cardiac cells is unknown. We demonstrate using adult cardiac fibroblasts that genetic deletion of GRK5 inhibits angiotensin II (AngII)-mediated fibroblast activation. Fibroblast-specific deletion of GRK5 in mice led to decreased fibrosis and cardiac hypertrophy after chronic AngII infusion or after ischemic injury compared to nontransgenic littermate controls (NLCs). Mechanistically, we show that nuclear translocation of GRK5 is involved in fibroblast activation. These data demonstrate that GRK5 is a regulator of fibroblast activation in vitro and cardiac fibrosis in vivo. This adds to previously published data which demonstrate the potential beneficial effects of GRK5 inhibition in the context of cardiac disease.