Uğur Özkan

Takotsubo syndrome (TTS), a transient left ventricular (LV) dysfunction typically precipitated by acute emotional or physical stress, is classically observed in individuals with structurally normal hearts. However, its occurrence in patients with established non-ischemic cardiomyopathy (NICMP) represents a striking clinical paradox that challenges our current understanding of both disease entities. This comprehensive review examines the complex pathophysiological mechanisms underlying this phenomenon, with particular emphasis on supraphysiological catecholamine surge and biased β-adrenergic receptor signaling, inflammatory-mediated sensitization, intrinsic mitochondrial dysfunction and mechanically-induced cytokine amplification.

Takotsubo syndrome (TTS) is a reversible form of acute cardiac syndrome usually arising in response to various emotional and physical stressors. TTS due to cardiac pacing has been an uncommon phenomenon mostly attributable to a variety of periprocedural conventional stressors including anxiety, pain and low cardiac output. Interestingly, intraventricular mechanical factors might also play a pivotal role in TTS evolution due to cardiac pacing. Notably, this phenomenon may be potentially underdiagnosed due to a variety of factors including atypical symptoms and masked electrocardiographic (ECG) changes potentially suggesting its higher incidence in clinical practice. The present paper aims to focus on mechanistic and clinical implications of TTS due to cardiac pacing procedures including conventional permanent pacemaker implantation (PPI) and conduction system pacing (CSP) along with a particular emphasis on intraventricular mechanical factors as potential TTS triggers in this context.

Objective: Aortic stenosis is a common valvular disease in the elderly. This study aimed to investigate changes in whole blood viscosity (WBV), which reflects hemodynamic load and blood flow and is associated with cardiovascular diseases, after percutaneous and surgical interventions for aortic stenosis. Methods: From 2019 to 2022, 200 patients undergoing Transcatheter Aortic Valve Implantation (TAVI) (n = 100) or bioprosthetic Aortic Valve Replacement (bAVR) (n = 100) were analyzed. WBV at low shear rate (LSR, 0.5 s ⁻¹ ) and high shear rate (HSR, 208 s ⁻¹ ) was calculated from the hematocrit and total protein using the De Simone formula. Pre- and 3-month values were compared using paired and independent t-tests, and correlations and multivariable regression were performed. Results: The aortic valve area was negatively correlated with HSR (r = –0.340, p < 0.01) and LSR (r = –0.358, p < 0.01). At 3 months, HSR decreased by 0.95 ± 0.31 cP and LSR by 18.92 ± 6.32 cP (both p < 0.001). Reductions were significant in both groups without between-group differences and were mainly related to decreases in non-albumin protein fractions. Conclusion: Both TAVI and bAVR markedly reduced WBV, independent of the intervention type. WBV may be a useful biomarker for monitoring hemorheological and protein-based changes following valve intervention.

Atrial fibrillation (AF) is a common arrhythmia with substantial morbidity and a need for accessible markers that reflect disease burden, while olfactory dysfunction and chronic inflammation may share overlapping vascular and neuroinflammatory pathways. We aimed to evaluate olfactory function in patients with AF and to explore the role of systemic inflammation using the systemic immune-inflammation index (SII). In this single-center case–control study, 85 consecutively enrolled adults (AF group, n = 43; control group, n = 42) underwent olfactory assessment with the Sniffin’ Sticks Extended Test, including odor threshold (OT), odor discrimination (OD), and odor identification (OI), from which the threshold–discrimination–identification (TDI) score was derived; SII was calculated from same-day complete blood counts. Compared with controls, patients with AF had higher SII (878 [368–5769] vs. 503 [243–1450], p = 0.007) and lower OT (4 [1–8] vs. 5 [2–10], p = 0.001), OD (7 [4–12] vs. 13 [8–16], p < 0.001), OI (7.7 ± 2.6 vs. 12.6 ± 1.7, p < 0.001), and TDI scores (19 [10–29] vs. 29.5 [25–39], p < 0.001). Within the AF group, olfactory performance was inversely associated with symptom severity assessed by the European Heart Rhythm Association (EHRA) classification, and TDI was negatively correlated with SII. These findings indicate that AF is associated with impaired olfactory function and elevated systemic inflammation, supporting olfaction and inflammatory indices as potential correlates of symptom burden that warrant confirmation in larger prospective cohorts with standardized rhythm monitoring.

Non-obstructive myocardial stunning is characterized by transient myocardial contractile dysfunction despite preserved coronary perfusion. Although increas

Mast cell degranulation and other interacting and linked cells, including T-lymphocytes, macrophages, eosinophils, and platelets, as well as a range of inflammatory mediators produced during an anaphylactic or allergic reaction, constitute the main causes of Kounis syndrome. Acute ischemia episodes, coronary spasm, atheromatous plaque erosion/rupture, and platelet activation can all be caused by histamine, tryptase, arachidonic acid derivatives, and chymase in the Kounis syndrome cascade. Kounis syndrome can be triggered by a variety of factors, including medications, hymenopteran stings, metals, foods, environmental exposures, illnesses, and immunizations. In addition, some unusual, rare, intriguing, and significant causes of Kounis syndrome have been discovered recently, namely the “kiss of death”, where human kissing and pet kissing can induce fatal Kounis syndrome. Moreover, the clinical conundrum is that several of the main drugs and substances used to treat myocardial infarction and Kounis syndrome, such as adrenaline (epinephrine), aspirin, atropine, clopidogrel, corticosteroids, heparins, protamine sulfate, and hirudotherapy can also initiate it. Therefore, physicians should be aware of this clinical discrepancy to prevent catastrophic consequences.

This comprehensive review explores the critical roles of microRNAs (miRNAS) in cardiovascular diseases, emphasizing their regulatory functions in gene expression and their involvement in disease progression. miRNAS are small, evolutionarily conserved non-coding RNAs that regulate gene expression post-transcriptionally and play essential roles in various cardiac conditions, including fibrosis, cardiac remodeling, apoptosis, ischemia/reperfusion injury, hypertrophy, heart failure, arrhythmias, coronary artery disease (CAD), congenital heart diseases (CHDs), cardiomyopathies, and valvular heart disease (VHD). miRNAS are increasingly recognized as sensitive and specific biomarkers for early diagnosis, disease monitoring, and evaluation of therapeutic responses across the cardiovascular disease spectrum. Ischemia/reperfusion injury leads to significant cardiac damage through elevated oxidative stress, mitochondrial dysfunction, and apoptosis. CAD, a major contributor to global morbidity and mortality, is primarily driven by atherosclerosis and chronic inflammation. Cardiac hypertrophy is initially an adaptive response to stress but may progress to heart failure if sustained. Arrhythmias arise from electrical disturbances such as reentry, abnormal automaticity, and triggered activity. Heart failure is a complex and progressive syndrome marked by poor prognosis and increasing global prevalence. VHD involves intricate molecular alterations, including myocardial fibrosis and calcification, which contribute to disease progression and adverse outcomes. Cardiomyopathies—including hypertrophic, dilated, restrictive, and arrhythmogenic forms—are influenced by genetic mutations, systemic diseases, and disrupted molecular signaling. CHDs, the most common congenital malformations, stem from structural abnormalities in cardiac development and remain a major cause of infant morbidity and mortality. Novel therapeutic methods, such as antisense oligonucleotides, miR mimics, and exosome-based delivery mechanisms, demonstrate the translational promise of miRNAs in the realm of personalized cardiovascular medicine. However, issues such as small sample sizes, inconsistent results, interspecies differences, and delivery challenges restrict the clinical application of miRNA-based therapies. This review integrates mechanistic insights, critiques the quality of available evidence, and identifies translational shortcomings. It highlights the diagnostic, prognostic, and therapeutic potential of miRNAs in reshaping cardiovascular disease treatment.

Background and Objectives: Obstructive sleep apnea syndrome (OSAS) and heart failure (HF) frequently coexist, amplifying cardiovascular risk through mechanisms involving chronic inflammation and autonomic dysfunction. This study investigates the impact of systemic inflammation, measured by the systemic immune-inflammation index (SII), and OSAS severity, assessed by the apnea–hypopnea index (AHI), on myocardial repolarization heterogeneity in patients with both conditions. Materials and Methods: In this retrospective study, 160 patients with HF and polysomnography-confirmed OSAS (AHI ≥ 5 events/h) were evaluated between January 2018 and November 2024. Patients were stratified by QT dispersion (QTd < 40 ms vs. ≥40 ms) to assess electrical heterogeneity. SII was calculated from neutrophil, platelet, and lymphocyte counts, and electrocardiographic markers (QTd, frontal QRS-T angle, T wave peak-to-end interval [TPEI]) were measured. Logistic regression and receiver operating characteristic (ROC) analyses were used to identify predictors of repolarization heterogeneity and ventricular arrhythmias. Results: Patients with QTd ≥ 40 ms (n = 78) exhibited higher SII (p < 0.001) and AHI (p < 0.001) compared to those with QTd < 40 ms (n = 82). SII and AHI independently predicted increased QTd in multivariate analysis (p = 0.01 and p < 0.001, respectively). ROC analysis identified SII ≥ 625.4 (sensitivity 73.1%, specificity 72%) and AHI ≥ 22.4 (sensitivity 79.5%, specificity 79.3%) as optimal cut-offs for predicting repolarization heterogeneity. SII, QTd, and TPEI were significantly associated with ventricular arrhythmias (p < 0.05). Patients with moderate-to-severe OSAS (AHI ≥ 15) had higher rates of ventricular tachyarrhythmias (17.8% vs. 5.7%, p = 0.03) and sudden cardiac death (9.3% vs. 1.9%, p = 0.05). Conclusions: Elevated SII and AHI are independent predictors of myocardial repolarization heterogeneity in patients with HF and OSAS, contributing to increased arrhythmic risk. These findings highlight the potential use of SII and AHI as accessible biomarkers for risk stratification, particularly in patients with a preserved ejection fraction, and underscore the need for targeted interventions to mitigate inflammation and OSAS severity.

The degranulation of mast cells and other interacting and linked cells, including T-lymphocytes, macrophages, eosinophils, and platelets, as well as a range of inflammatory mediators produced during an anaphylactic or allergic reaction, are the main causes of Kounis syndrome. Acute ischemia episodes, coronary spasm, atheromatous plaque erosion/rupture, and platelet activation can all be caused by histamine, tryptase, arachidonic acid derivatives, and chymase in the Kounis syndrome cascade. Kounis syndrome is not a single-organ vascular disease, but rather a multisystem and multidisciplinary condition. Kounis syndrome can be brought on by a variety of factors, including medications, hymenopteran stings, metals, foods, environmental exposures, illnesses, and immunizations. In addition, some unusual, rare, intriguing, and significant causes of Kounis syndrome have been discovered recently. These include: The kiss of death where human kissing and pet kissing can induce fatal Kounis syndrome. Moreover, the clinical conundrum is that several of the main drugs and substances used to treat myocardial infarction and Kounis syndrome, including adrenaline (epinephrine), aspirin, atropine, clopidogrel, corticosteroids, heparins, protamine sulfate and hirudotherapy can also induce it. Therefore, physicians should be aware of this clinical discrepancy to prevent catastrophic undesirable circumstances.