Pathophysiological aspects of development myocardial infarction type 2 in subclinical hypothyroidism

The main purpose of the following article is to highlight one of the most pressing and poorly studied issues both for cardiology and endocrinology – treatment and prognosis for patients with severe coronary pathology and subclinical hypothyroidism (SH). Pathophysiological mechanisms of type 2 myocardial infarction (MI) development with SH as a background and hormone replacement therapy issues are considered. SH is a modifiable risk factor (RF) for cardiovascular diseases (CVD) and mortality that does not depend on traditional cardiovascular RF. SH is associated with high risk of developing coronary artery disease, MI, heart failure, and CVD mortality. SH incidence of morbidity increases with age, usually the course is oligo- or asymptomatic. SH leads to a number of pathological conditions that cause an imbalance between the myocardial oxygen demand and delivery with a possible development of type 2 MI. Clinical case of type 2 MI development in a patient with severe coronary atherosclerosis and SH is presented. The key point of type 2 MI development mechanism is insufficient oxygen (O2) supply to cardiomyocytes due to multivessel coronary artery atherosclerotic stenosis and sharp increase in O2 demand as a result of cardiomyocyte hypertrophy. Older patients with severe cardiac pathology and SH should refrain from treatment with levothyroxine or start treatment after myocardial revascularization, selecting the dose of the drug individually.

Mechanobiology of Microvascular Function and Structure in Health and Disease: Focus on the Coronary Circulation

The coronary microvasculature plays a key role in regulating the tight coupling between myocardial perfusion and myocardial oxygen demand across a wide range of cardiac activity. Short-term regulation of coronary blood flow in response to metabolic stimuli is achieved via adjustment of vascular diameter in different segments of the microvasculature in conjunction with mechanical forces eliciting myogenic and flow-mediated vasodilation. In contrast, chronic adjustments in flow regulation also involve microvascular structural modifications, termed remodeling. Vascular remodeling encompasses changes in microvascular diameter and/or density being largely modulated by mechanical forces acting on the endothelium and vascular smooth muscle cells. Whereas in recent years, substantial knowledge has been gathered regarding the molecular mechanisms controlling microvascular tone and how these are altered in various diseases, the structural adaptations in response to pathologic situations are less well understood. In this article, we review the factors involved in coronary microvascular functional and structural alterations in obstructive and non-obstructive coronary artery disease and the molecular mechanisms involved therein with a focus on mechanobiology. Cardiovascular risk factors including metabolic dysregulation, hypercholesterolemia, hypertension and aging have been shown to induce microvascular (endothelial) dysfunction and vascular remodeling. Additionally, alterations in biomechanical forces produced by a coronary artery stenosis are associated with microvascular functional and structural alterations. Future studies should be directed at further unraveling the mechanisms underlying the coronary microvascular functional and structural alterations in disease; a deeper understanding of these mechanisms is critical for the identification of potential new targets for the treatment of ischemic heart disease.

Dynamic Handgrip Exercise: Feasibility and Physiologic Stress Response of a Potential Needle-Free Cardiac Magnetic Resonance Stress Test

Background: Cardiac magnetic resonance (CMR) pharmacological stress-testing is a well-established technique for detecting myocardial ischemia. Although stressors and contrast agents seem relatively safe, contraindications and side effects must be considered. Substantial costs are further limiting its applicability. Dynamic handgrip exercise (DHE) may have the potential to address these shortcomings as a physiological stressor. We therefore evaluated the feasibility and physiologic stress response of DHE in relation to pharmacological dobutamine-stimulation within the context of CMR examinations.Methods: Two groups were prospectively enrolled: (I) volunteers without relevant disease and (II) patients with known CAD referred for stress-testing. A both-handed, metronome-guided DHE was performed over 2 min continuously with 80 contractions/minute by all participants, whereas dobutamine stress-testing was only performed in group (II). Short axis strain by fast-Strain-ENCoded imaging was acquired at rest, immediately after DHE and during dobutamine infusion.Results: Eighty middle-aged individuals (age 56 ± 17 years, 48 men) were enrolled. DHE triggered significant positive chronotropic (HRrest: 68 ± 10 bpm, HRDHE: 91 ± 13 bpm, p < 0.001) and inotropic stress response (GLSrest: −19.4 ± 1.9%, GLSDHE: −20.6 ± 2.1%, p < 0.001). Exercise-induced increase of longitudinal strain was present in healthy volunteers and patients with CAD to the same extent, but in general more pronounced in the midventricular and apical layers (p < 0.01). DHE was aborted by a minor portion (7%) due to peripheral fatigue. The inotropic effect of DHE appears to be non-inferior to intermediate dobutamine-stimulation (GLSDHE= −19.5 ± 2.3%, GLSDob= −19.1 ± 3.1%, p = n.s.), whereas its chronotropic effect was superior (HRDHE= 89 ± 14 bpm, HRDob= 78 ± 15 bpm, p < 0.001).Conclusions: DHE causes positive ino- and chronotropic effects superior to intermediate dobutamine-stimulation, suggesting a relevant increase of myocardial oxygen demand. DHE appears to be safe and timesaving with broad applicability. The data encourages further studies to determine its potential to detect obstructive CAD.

Abstract 9160: Epinephrine-Dominant versus Non-Epinephrine Dominant Resuscitation for In-Hospital Cardiac Arrest

Introduction: Vasopressors are used during CPR to increase arterial resistance and aortic diastolic pressure, improving coronary perfusion and likelihood of ROSC. In comparison to epinephrine, vasopressin remains effective in an acidemic environment, has favorable cerebral perfusion, and does not directly increase myocardial oxygen demand. Studies comparing epinephrine and vasopressin report variable ROSC, survival, and neurological outcome. Most studies used few vasopressin doses and it is unclear whether greater vasopressin use leads to clinical benefit. Hypothesis: We hypothesized that a non-epinephrine dominant CPR approach with vasopressin would lead to greater ROSC than an epinephrine-dominant approach. Methods: This was a retrospective, single-center study conducted at an 800-bed academic medical center. All first cardiac arrests among adult inpatients between Jan 2018 and Mar 2021 were screened, and those with at least 2 vasopressor doses used were included. Patients who received epinephrine-dominant resuscitation (epinephrine-to-vasopressin dose ratio >2 or CPR using only epinephrine) were compared to patients who received a non-epinephrine dominant approach (epinephrine-to-vasopressin dose ratio ≤2). The incidence of ROSC was analyzed using a Chi-squared test where p <0.05 was considered significant. Secondary outcomes included survival to discharge with favorable neurologic outcome, survival to discharge, and Cerebral Performance Category scores. Results: Of 663 in-hospital cardiac arrests screened, 264 were included. Two hundred twenty-eight (86%) presented with PEA/asystole as the initial rhythm, and the most common etiologies were circulatory (41%) and respiratory (26%). The epinephrine-dominant arm achieved ROSC in 89 (66%) patients compared to 87 (67%) patients in the non-epinephrine dominant arm (RR 0.99, 95% CI 0.84-1.18, p=0.93). Survival to discharge was higher in the epinephrine-dominant arm (25% vs 15%, p=0.04). Conclusion: There was no difference in ROSC between epinephrine-dominant and non-epinephrine dominant resuscitation for adult in-hospital cardiac arrest. Future studies should examine the impact of non-epinephrine dominant CPR on long term neurologic outcomes.

Characteristics of clinical signs, laboratory and instrumental examinations in various mechanisms of development of type 2 myocardial infarction

Aim. To identify different pathogenetic variants of myocardial infarction type 2 (MI-2). Material and methods. Reviewed 4168 cases of MI admitted in multidisciplinary hospital for 10 years. 353 patients met the criteria for MI-2 without signs of coronary atherothrombosis (CA). In the study group, the features of clinical and laboratory-instrumental manifestations were evaluated. Results. Cases of IM-2 were subdivided into 4 clinical-pathogenic variants (CPV): 1-CPV developed due an increasing in myocardial oxygen demand; 2-CPV, arising from a decrease in the supply of oxygen; 3-CPV associated with local coronary circulation disorder; 4-CPV developed due to the combined oxygen-energy imbalance. In 72 (20.4%) cases, 1-CPV was detected, caused by a hypertensive crisis and/or tachyarrhythmias; 2-CPV observed in 73 (20.68%) patients with hypotension, anemia, microvascular dysfunction, respiratory failure; 3-CPV caused by spasm and embolism of CA was detected in 47 (13.31%) cases; in 161 (45.61%) patients, IM-2 is associated with increased myocardial oxygen demand with reduced oxygen delivery. The gender and risk factors in groups are comparable. The average age of 1-CPV- and 3-CPV-patients was less and amounted to 65.7 and 56.5 versus 70.2 and 73.8 years in the 2-CPV and 4-CPV. Typical clinical and laboratory-instrumental signs of MI were common for patients with 1-CPV and 3-CPV, while 2-CPV and 4-CPV more often had chronic severe pathology, multivessel coronary disorder, and the clinical presentation and ischemic signs were less common. Conclusion. Clinical manifestations and results of examination of patients with MI-2 depend on the mechanism of its development.

Incomplete functional reverse remodelling of the left ventricle one year after bariatric surgery. Insights from the prospective FatWest study

Background Patients with severe obesity are predisposed to development of left ventricular (LV) hypertrophy with subsequent increased myocardial oxygen demand and impaired myocardial function. Bariatric surgery leads to rapid weight loss and improves cardiovascular risk profile. Purpose To assess whether LV systolic function, wall mechanics, and cardiac power improve 1 year after bariatric surgery. Methods 91 severely obese patients (43±10 years, 70% women, body mass index [BMI] 41.7±4.9 kg/m2, 55% with hypertension, 17% with diabetes mellitus) underwent echocardiography before, 6 and 14 months after Roux-en-Y gastric bypass surgery in the prospective FatWest (Bariatric Surgery on the West Coast of Norway) study. We assessed LV systolic function by biplane ejection fraction (EF), LV wall mechanics by midwall shortening (MWS) and global longitudinal strain (GLS), and cardiac power normalized for LV mass by 0.222 x cardiac output x mean blood pressure (BP)/LV mass. Results Surgery induced a significant reduction in BMI, heart rate, systolic BP, and LV mass (Figure 1). Prevalence of LV hypertrophy fell from 34 to 20% 14 months after surgery (p&lt;0.001), while that of concentric geometry remained stable: 8 vs 10% (p=0.36). GLS improved by 28%, however LV EF and MWS did not change (Figure 2). LV power at rest decreased postoperatively, reflecting the lower BP and heart rate, but was unaltered when normalized for LV mass (Figure 2). In backward stepwise multivariate regression analyses, 1 year improvement in GLS was predicted by the systolic BP reduction (p&lt;0.05) (R2 0.73, p&lt;0.001), while low 1-year MWS was independently associated with female gender, concentric geometry and higher myocardial oxygen demand (all p&lt;0.01) (Nagelkerke R2 0.44, p&lt;0.001), and lower 1-year LV power-mass with female gender and LV hypertrophy (p&lt;0.01) (R2 0.24, p&lt;0.001). Conclusion In severely obese patients, LV longitudinal function normalizes 1 year after bariatric surgery, mainly due to the BP reduction. LV midwall mechanics and power do not improve, especially in women and patients with persistent LV geometric abnormalities. FUNDunding Acknowledgement Type of funding sources: None. Figure 1 Figure 2

Clinical Assessment of Ventricular Wall Stress in Understanding Compensatory Hypertrophic Response and Maladaptive Ventricular Remodeling

Ventricular wall stress (WS) is an important hemodynamic parameter to represent myocardial oxygen demand and ventricular workload. The normalization of WS is regarded as a physiological feedback signal that regulates the rate and extent of ventricular hypertrophy to maintain myocardial homeostasis. Although hypertrophy is an adaptive response to increased biomechanical stress, persistent hypertrophic stimulation forces the stressed myocardium into a progressive maladaptive process called ventricular remodeling, consisting of ventricular dilatation and dysfunction in conjunction with the development of myocyte hypertrophy, apoptosis, and fibrosis. The critical determinant of this pathological transition is not fully understood, but an energetic mismatch due to uncontrolled WS is thought to be a central mechanism. Despite extensive basic investigations conducted to understand the complex signaling pathways involved in this maladaptive process, clinical diagnostic studies that translate these molecular and cellular changes are relatively limited. Echocardiographic assessment with or without direct measurement of left ventricular pressure used to be a mainstay in estimating ventricular WS in clinical medicine, but in recent years more and more noninvasive applications with magnetic resonance imaging have been studied. In this review article, basic clinical applications of WS assessment are discussed to help understand the progression of ventricular remodeling.

Acute coronary syndrome in COVID-19 patients

Acute coronary syndrome (ACS) is caused by an acute mismatch between myocardial oxygen demand and its supply. This mechanism is largely associated with the progression of coronary atherosclerosis in combination with an inflammatory response, hypoxemia, and blood procoagulation. Patients with the coronavirus disease 2019 (COVID-19), aggravated by cardiovascular diseases and comorbidities, are at high risk of ACS.Aim. To analyze the publications, which reflects the development of ACS in patients with COVID-19, its pathogenesis, and clinical course. Material and methods. Literature data were searched using Google Scholar, PubMed, ScienceDirect, and Cyberleninka services. The analysis included data from clinical guidelines on COVID-19, data from clinical studies, reports, and systematic reviews.Results. This literature review summarizes and systematizes the data presented in modern publications, highlights the aspects of the clinical course and pathogenetic mechanisms underlying ACS in patients with COVID-19.Conclusion. The pathogenesis of COVID-19 is inextricably associated with the widespread cytopathic effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), uncontrolled immune response that causes systemic inflammation, as well as the coagulation system activation. In patients with COVID-19, along with the atherosclerosis, these mechanisms significantly increase the risk of ACS and can worsen its in-hospital course.

Comparison Between Invasive and Noninvasive Methods to Estimate Subendocardial Oxygen Supply and Demand Imbalance

Background Estimation of the balance between subendocardial oxygen supply and demand could be a useful parameter to assess the risk of myocardial ischemia. Evaluation of the subendocardial viability ratio (SEVR, also known as Buckberg index) by invasive recording 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 its noninvasive estimation and the demonstration of its reliability. Methods and Results 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 intra‐ventricular 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 the novel method for SEVR assessment tested in this study. SEVR values estimated with carotid tonometry by "traditional” and "new” method were compared with those evaluated invasively by cardiac catheterization. The “traditional” method provided significantly higher SEVR values than the reference invasive SEVR: average of differences±SD= 44±11% (limits of agreement: 23% – 65%). The noninvasive “new” method showed a much better agreement with the invasive determination of SEVR: average of differences±SD= 0±8% (limits of agreement: ‐15% to 16%). Conclusions Carotid applanation tonometry provides valid noninvasive SEVR values only when all the main factors determining myocardial supply and demand flow are considered.

One-year impact of bariatric surgery on left ventricular mechanics: results from the prospective FatWest study

Aims Patients with severe obesity are predisposed to left ventricular (LV) hypertrophy, increased myocardial oxygen demand, and impaired myocardial mechanics. Bariatric surgery leads to rapid weight loss and improves cardiovascular risk profile. The present prospective study assesses whether LV wall mechanics improve 1 year after bariatric surgery. Methods and results Ninety-four severely obese patients [43 ± 10 years, 71% women, body mass index (BMI) 41.8 ± 4.9 kg/m2, 57% with hypertension] underwent echocardiography before, 6 months and 1 year after gastric bypass surgery in the FatWest (Bariatric Surgery on the West Coast of Norway) study. We assessed LV mechanics by midwall shortening (MWS) and global longitudinal strain (GLS), LV power/mass as 0.222 × cardiac output × mean blood pressure (BP)/LV mass, and myocardial oxygen demand as the LV mass-wall stress-heart rate product. Surgery induced a significant reduction in BMI, heart rate, and BP (P &lt; 0.001). Prevalence of LV hypertrophy fell from 35% to 19% 1 year after surgery (P &lt; 0.001). The absolute value of GLS improved by—4.6% (i.e. 29% increase in GLS) while LV ejection fraction, MWS, and LV power/mass remained unchanged. In multivariate regression analyses, 1 year improvement in GLS was predicted by lower preoperative GLS, larger mean BP, and BMI reduction (all P &lt; 0.05). Low 1-year MWS was associated with female sex, preoperative hypertension, and higher 1-year LV relative wall thickness and myocardial oxygen demand (all P &lt; 0.001). Conclusion In severely obese patients, LV longitudinal function is largely recovered one year after bariatric surgery due to reduced afterload. LV midwall mechanics does not improve, particularly in women and patients with persistent LV geometric abnormalities. ClinicalTrials.gov identifier NCT01533142, 15 February 2012.