Combined administration of nicorandil and atorvastatin in patients with acute myocardial infarction after coronary intervention, and its effect on postoperative cardiac systolic function

Purpose: To study the effect of a combination of nicorandil and atorvastatin calcium in patients with acute myocardial infarction after coronary intervention, and its effect on postoperative cardiac systolic function of patients.Methods: Retrospective analysis was performed on 100 patients with acute myocardial infarctiontreated with coronary interventional therapy in The Third Affiliated Hospital of Qiqihaer MedicalUniversity from April 2019 to August 2020. The patients were randomised into control and study groups, with 50 patients in each group. The control group was treated with nicorandil, while the study group was treated with a combination of nicorandil and atorvastatin. Treatment response, cardiac structural indices, cardiac systolic function, blood lipid profiles, quality of life (QLI) score, Barthel Index (BI), Fugl- Meyer assessment (FMA), motor function score, incidence of adverse reactions, and blood pressure changes on days 1, 2, 3 and 4 after surgery, were compared between the two groups.Results: Treatment effectiveness, cardiac systolic function, QLI score, BI index and FMA motor function score in the study group were higher than the corresponding control values (p < 0.05). However, lower cardiac structure indices, blood lipid profiles and incidence of adverse reactions were greater in the study group than in the control group (p < 0.05). No significant disparity in blood pressure was found between the two groups on post-surgery days 1, 2, 3 and 4.Conclusion: The combination of nicorandil and atorvastatin calcium tablets produced better outcomes in patients with acute myocardial infarction after coronary intervention therapy; furthermore, the combination therapy significantly improved the cardiac systolic function of patients.

EVALUATION OF CARDIAC SYSTOLIC FUNCTION IN ASYMPTOMATIC DIABETES PATIENTS AND ITS CORRELATION WITH DURATION OF DIABETES

Echocardiography is a universally availabe and economical test for detecting early LV systolic dysfunction in normotensive and asymptomatic type 2 diabetic patients. This is a cross sectional study of such patients evaluating cardiac systolic function using 2D-Echocardiography. Ejection fraction and Fractional shortening are the two most sensitive indicators of it. Only 18% of patients had decreased LVEf and 6% showed reduced fractional shortening . Although longer duration of diabetes was positively correlated with reduction in systolic functioning of heart. Early identification of subclinical signs of heart failure by these noninvasive and less expensive methods may improve outcomes in type 2 diabetes patients.

Effect of SGLT2 inhibition on coronary microvascular function in patients with type 2 diabetes

Background Treatment with sodium-glucose cotransporter 2 (SGLT2) inhibitor reduces risk of cardiovascular death and heart failure but the underlying mechanisms remain poorly understood. It has been suggested that a shift in fuel source in the myocardium from glucose and free fatty acids to the more energy efficient ketogenesis reduces oxidative stress involved in coronary microvascular damage, leading to improved coronary microvascular function. Purpose To test the hypothesis that treatment with the SGLT2 inhibitor empagliflozin improves non-endothelial dependent coronary microvascular function. Methods We included 26 patients with type 2 diabetes in a double blinded, placebo-controlled cross-over study. Participants were treated with empagliflozin 25 mg and placebo for 12 weeks, interrupted by 2 weeks wash-out period. The primary outcome was change in coronary microvascular function, assessed as coronary flow velocity reserve (CFVR) and measured with transthoracic doppler echocardiography. Secondary endpoints were change in echocardiographic parameters of cardiac systolic function and 184 cardiovascular protein biomarkers. Results Nineteen patients completed both study periods according to protocol. There was a significant weight loss and reduction in Hba1c after empagliflozin treatment (table). We found no improvement in CFVR and parameters of cardiac systolic function. We observed a general tendency of reduction in level of cardiovascular biomarkers after empagliflozin treatment (figure) with significant difference between empagliflozin and placebo for 27 proteins, including IL18, ST2, YKL40, ACE2 and leptin. Conclusions Despite a significant weight loss and reduction in Hba1c after empagliflozin treatment, we found no effect on non-endothelial dependent coronary microvascular function in patients with type 2 diabetes mellitus. Improvement in multiple biomarkers may indicate underlying mechanisms but need confirmation in larger studies. FUNDunding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The Danish Council for Independent Research Table 1. Change in outcome parameters Figure 1. Change in biomarker levels

Exercise intolerance in volume overload heart failure is associated with low carotid body mediated chemoreflex drive

Mounting an appropriate ventilatory response to exercise is crucial to meeting metabolic demands, and abnormal ventilatory responses may contribute to exercise-intolerance (EX-inT) in heart failure (HF) patients. We sought to determine if abnormal ventilatory chemoreflex control contributes to EX-inT in volume-overload HF rats. Cardiac function, hypercapnic (HCVR) and hypoxic (HVR) ventilatory responses, and exercise tolerance were assessed at the end of a 6 week exercise training program. At the conclusion of the training program, exercise tolerant HF rats (HF + EX-T) exhibited improvements in cardiac systolic function and reductions in HCVR, sympathetic tone, and arrhythmias. In contrast, HF rats that were exercise intolerant (HF + EX-inT) exhibited worse diastolic dysfunction, and showed no improvements in cardiac systolic function, HCVR, sympathetic tone, or arrhythmias at the conclusion of the training program. In addition, HF + EX-inT rats had impaired HVR which was associated with increased arrhythmia susceptibility and mortality during hypoxic challenges (~ 60% survival). Finally, we observed that exercise tolerance in HF rats was related to carotid body (CB) function as CB ablation resulted in impaired exercise capacity in HF + EX-T rats. Our results indicate that: (i) exercise may have detrimental effects on cardiac function in HF-EX-inT, and (ii) loss of CB chemoreflex sensitivity contributes to EX-inT in HF.

Exercise Intolerance in Volume Overload Heart Failure Is Associated With Low Carotid Body Chemosensitivity

Mounting an appropriate ventilatory response to exercise is crucial to meeting metabolic demands during exercise and abnormal ventilatory responses may contribute to exercise-intolerance (EX-inT) in HF patients. We sought to determine if abnormal ventilatory chemoreflex control contributes to EX-inT in volume-overload HF rats. Cardiac function, hypercapnic (HCVR) and hypoxic (HVR) ventilatory responses and exercise tolerance were assessed at the end of a 6 weeks exercise training program. Exercise tolerant HF rats (HF+EX-T) completed all training sessions and benefit from exercise as evidenced by improvements in cardiac systolic function and reductions in HCVR, sympathetic tone and arrhythmias. Contrarily, HF rats that failed to complete training sessions (HF+EX-inT) showed no improvements in cardiac systolic function nor in HCVR, sympathetic tone, or arrhythmias but displayed a further compromise in cardiac diastolic function when compared to HF-sedentary rats. In addition, HF+EX-inT rats showed impaired HVR which was associated with increased arrhythmias susceptibility and mortality during hypoxic challenges (~60% survival). Finally, exercise tolerance was closely dependent on carotid body (CB) function since their selective ablation impaired exercise capacity in HF. Our results indicate that: i) exercise may have detrimental effects on cardiac function in HF-EX-inT, and ii) reduced CB chemoreflex contributes to EX-inT in HF.

Antiarrhythmic Properties of Phenytoin

BACKGROUND: Phenytoin has long been used to treat epilepsy and for some time as an antiarrhythmic drug (AAD). It is known that the diastolic calcium leakage through dysfunctional cardiac ryanodine receptors (RyR2) is a mechanism for arrhythmias in heart failure. Recent evidence suggests that phenytoin inhibits dysfunctional RyR2, reduces the calcium leak during diastole in heart failure, and may improve cardiac systolic function. This indicates the potential for repurposing phenytoin as an AAD in patients with heart failure.METHODS: A systematic search of MEDLINE, Embase, and the Cochrane Library databases was performed in March 2019. The search was limited to the studies published in the English language from 1946 to 2019. Studies on the antiarrhythmic effects of phenytoin in adults compared to no treatment or other AADs were included. Studies were excluded if there was insufficient clinical data regarding antiarrhythmic effects, dosing and administration of phenytoin and other ADDs. Conference abstracts, editorials, case studies and review articles were also excluded. RESULTS: A total of 157 non-duplicate titles were screened, and 25 articles underwent full-text review. 13 studies met the inclusion criteria, representing a total of 985 patients. Phenytoin was found to be effective in treating arrhythmias associated with digitalis toxicity, and in suppressing premature ventricular contractions (PVCs). In a recent animal study, phenytoin inhibited diastolic calcium leak through dysfunctional RyR2 in failing sheep hearts and improved cardiac systolic function without affecting normal functional RyR2.CONCLUSION: Phenytoin has an acceptable safety profile when used as an AAD. It has some utility in treating digitalis-induced arrhythmias and suppressing PVCs, however, further study is needed to determine its efficacy as an antiarrhythmic in heart failure patients given new evidence of its RyR2 stabilising properties.TRIAL REGISTRATION NUMBER: PROSPERO database (CRD42019129125).

Index of microcirculatory resistance predicts long term cardiac systolic function in patients with STEMI undergoing primary PCI

Background To evaluate the predictive value of the index of microcirculatory resistance (IMR) for long-term cardiac systolic function after primary percutaneous coronary intervention (pPCI) in patients with acute anterior wall ST-segment elevation myocardial infarction (STEMI). Methods A total of 53 acute anterior wall STEMI patients were included and followed up within 1-year. IMR was measured to evaluate the immediate intraoperative reperfusion. IMR > 40 U was defined as the high IMR group and ≤ 40 U was defined as the low IMR group. Left ventricular ejection fraction (LVEF) was measured by echocardiography at 24 h, 1 month, 3 months, and 1 year after PCI to analyze the correlation between IMR and cardiac systolic function. Heart failure was estimated according to classification within one year. Results The ratio of TMPG (TIMI myocardial perfusion grade) 3 (85.7% vs. 52%, p = 0.015) and STR (ST-segment resolution) > 70% (82.1% vs. 48%, p = 0.019) were significantly higher in the low IMR group. The LVEF in the low IMR group was significantly higher than that in the high IMR group at 3 months (43.06 ± 2.63% vs. 40.20 ± 2.67%, p < 0.001) and 1 year (44.16 ± 2.40% vs. 40.13 ± 3.48%, p < 0.001). IMR was negatively correlated with LVEF at 3 months (r = − 0.1014, p = 0.0040) and 1 year (r = − 0.1754, p < 0.0001). Conclusions The IMR showed significant negative correlation with the LVEF value after primary PCI. The high IMR is a strong predictor of heart failure within 1 year after anterior myocardial infarction.

Early Left Ventricular Global Longitudinal Strain Deterioration After Aortic Aneurysm Repair: Impact of Aortic Stiffness

Purpose To associate the impact of aortic reconstruction using currently available grafts and endografts on pulse wave velocity in patients with abdominal aortic aneurysm (AAA) and to evaluate its effect on early cardiac systolic function indices. Materials and Methods Seventy-three consecutive patients with AAA (mean age 70±8 years; all men) who underwent open (n=12) or endovascular repair (EVAR; n=61) were prospectively enrolled in an observational cohort study. Left ventricular global longitudinal strain (GLS; an important diagnostic and prognostic index of early systolic dysfunction) and carotid-femoral pulse wave velocity (cf-PWV) were estimated 1 week preoperatively, as well as at 1 and 6 months postoperatively. Results A significant time effect was found for cf-PWV, which showed an increase at 1 month that remained through 6 months (p=0.007). Additionally, a deterioration in GLS values was revealed, with a significant change at 1 month that persisted 6 months later (p<0.001). No significant group effect was observed between EVAR and open repair (p=0.98), and there was no significant interaction (p=0.96). Notably, the difference in GLS between baseline and 6 months significantly correlated with the corresponding changes in cf-PWV (r=0.494, p<0.001). Conclusion AAA repair leads not only to an increase in aortic stiffness, as measured by the increase in pulse wave velocity, but also to reduced cardiac systolic function. Our findings highlight the need for a more intense cardiac surveillance program after aortic reconstruction. Further studies are needed to investigate how this may translate into long-term manifestations of cardiovascular complications and symptomatology.