BACKGROUND:Right ventricular-pulmonary artery (RVPA) coupling is an emerging prognostic marker in cardiovascular disease, but its predictive value in patients undergoing mitral transcatheter edge-to-edge repair (MTEER) remains uncertain. METHODS:We conducted a systematic review and meta-analysis following PRISMA 2020 guidelines. PubMed, Scopus, and Web of Science were searched for studies evaluating the prognostic impact of RVPA coupling in patients undergoing MTEER, using tricuspid annular plane systolic excursion (TAPSE)/pulmonary artery systolic pressure (PASP) or related markers. Risk of bias was assessed with the ROBINS-I tool, and meta-analyses were used to evaluate associations with clinical outcomes, including all-cause mortality, major adverse cardiovascular events (MACE), and residual mitral regurgitation (MR). RESULTS:Nine studies involving 3281 patients were included. Baseline RVPA uncoupling was significantly associated with an increased incidence of MACE (risk ratio [RR] 1.75, 95% confidence interval [CI]: 1.40-2.19) and higher all-cause mortality (RR 1.82, 95% CI: 1.53-2.18). No significant association was observed with post-operative MR (RR 1.17, 95% CI: 0.83-1.63). Sensitivity analyses did not alter the direction of the findings. CONCLUSION:RVPA uncoupling is associated with adverse outcomes after MTEER. Routine assessment may improve pre-procedural risk stratification. Further studies should refine diagnostic thresholds and evaluate potential therapeutic strategies in the setting of impaired RVPA coupling prior to MTEER.

Coronary microvascular dysfunction (CMD) constitutes an increasingly acknowledged aspect of coronary artery disease. Even though traditional cardiovascular risk factors have been implicated in CMD pathogenesis, data on lipoprotein (a) [Lp(a)] is limited. This cross-sectional study aimed to investigate whether Lp(a) levels are associated with CMD in patients with angina and nonobstructive coronary arteries. Coronary physiology assessment was performed with the standard bolus thermodilution technique, allowing for coronary flow reserve (CFR) and index of microvascular resistance estimation. Participants were categorized into 3 groups based on Lp(a) levels (<30, [30 to 50], and ≥50 mg/dl) as well as into 2 groups based on the presence of CMD. CMD was defined as CFR ≤2.5 and/or index of microvascular resistance ≥25. A total of 127 patients were recruited. No significant differences in baseline characteristics were observed between the groups. In unadjusted analysis, no significant associations were found. In multivariable analysis adjusting for age and sex, participants with Lp(a) values ≥50 mg/dl displayed a trend for a 4.25 increased CMD risk when compared to participants with Lp(a) values <30 mg/dl (odds ratio 4.25, confidence interval 0.81 to 22.28, p = 0.087). The same group of patients tended to have lower CFR than controls with Lp(a) <30 mg/dl, with a median CFR that was 1.05 units lower (p = 0.086). In conclusion, patients with high Lp(a) levels tended to display a higher prevalence of CMD and lower CFR. More studies are needed in order to better elucidate the relationship between Lp(a) and CMD.

Coronary microvascular dysfunction (CMD) is increasingly recognized as a significant cardiovascular condition, particularly among women, yet its diagnosis and management during pregnancy remain poorly understood. CMD may arise de novo in the context of hypertensive disorders of pregnancy or represent an exacerbation of pre-existing endothelial dysfunction. This article views current evidence surrounding CMD in pregnancy, outlines the limitations of current diagnostic and treatment approaches, and highlights critical research gaps that must be addressed to improve outcomes in this vulnerable population.

INTRODUCTION:Blood pressure variability (BPV) is a prognostic marker in hypertension and coronary artery disease (CAD), but its role in acute myocardial infarction (AMI) remains unknown. This study assessed the association of short-term (24-h ambulatory BP monitoring, ABPM) and mid-term BPV with adverse in-hospital and long-term outcomes in AMI patients. METHODS:Mid-term BPV was calculated as the standard deviation (SD) of daily in-hospital BP readings; short-term BPV was measured by average real variability (ARV) from ABPM. Patients were evaluated as continuous variables and by quartiles (Q1-Q4). Logistic regression and Cox models assessed in-hospital and 3-year outcomes. RESULTS:In this prospective, single-center cohort, 441 of 677 AMI patients were included. Each 1 mmHg rise in day-to-day systolic BPV (SBP-SD) increased in-hospital MACE risk by 24% [odds ratio (OR): 1.24, 95% confidence interval (CI): 1.17-1.31], with Q4 showing the highest risk (OR: 28.89, 95% CI: 8.58-97.28). ABPM-derived SBP-ARV predicted in-hospital mortality (OR: 1.58, 95% CI: 1.21-2.07) and MACE (OR: 1.35, 95% CI: 1.23-1.48). Diastolic ARV was linked to in-hospital myocardial infarction (MI), arrhythmias, and shock. At 3-year follow up, Q4 of SBP-SD showed higher risk of composite outcomes (hazard ratio: 29.88, 95% CI: 10.93-81.66) and all-cause mortality (hazard ratio: 11.85, 95% CI: 2.81-49.91). SBP-ARV independently predicted both all-cause mortality (hazard ratio: 1.37, 95% CI: 1.25-1.51) and adverse events (hazard ratio: 1.29, 95% CI: 1.22-1.36), while diastolic BPV was primarily associated with arrhythmias and heart failure hospitalization. CONCLUSION:Systolic BPV independently predicts in-hospital and long-term outcomes in AMI. BPV assessment may aid post-MI risk stratification and guide novel therapeutic strategies in this high-risk population.

BACKGROUND:The association of epicardial obstructive coronary artery disease with major adverse cardiovascular events (MACE) is established; however, accumulating evidence emphasizes the significant role of coronary microvascular dysfunction (CMD). The aim of this meta-analysis is to summarize the available evidence on the prognostic effect of CMD in cardiovascular outcomes and mortality. METHODS:Systematic literature search in MEDLINE/PubMed and Scopus was conducted to identify studies comparing the prognosis of CMD vs non-CMD using coronary flow reserve (CFR) and/or index of microcirculatory resistance (IMR) invasive indices. A meta-analysis to calculate pooled risk ratios (RR) was performed along with sensitivity and meta-regression analyses. RESULTS:Thirty-one studies were included (n = 13,016, weighted mean age 58 years, males 57%, left ventricular ejection fraction 58%, CFR 2.6, IMR 24.4, CMD 33%). Meta-analysis of 24 studies (n = 8294) indicated a pooled RR for MACE of 2.55 (2.11, 3.10) for CMD vs non-CMD comparison. Consistent findings were observed for all-cause [1.88 (1.52, 2.33)] and cardiovascular mortality [2.76 (2.02, 3.76)], myocardial infarction [2.18 (1.56, 3.05)], revascularization [1.67 (1.06, 2.64)], heart failure hospitalization [3.46 (1.90, 6.30)], and stroke risk [1.85 (1.26, 2.71)]. The CFR and IMR-based analyses provided similar findings. Worse outcomes were observed in acute coronary syndrome patients and in those with the structural CMD endotype (abnormal CFR/abnormal IMR). CONCLUSION:Invasively diagnosed CMD is associated with a 2.5-fold increase in MACE and a 3-fold increase in cardiovascular mortality. This finding highlights the importance of a more comprehensive assessment of coronary vasculature, including both the macro- and the microcirculation.

Myocardial infarction with non-obstructive coronary arteries (MINOCA) accounts for approximately 5–15% of all myocardial infarctions and disproportionately affects women. Once treated as a diagnosis of exclusion, MINOCA is now recognised as a heterogeneous, mechanism-based syndrome encompassing atherosclerotic plaque disruption, epicardial and microvascular vasospasm, microvascular dysfunction, coronary thromboembolism, and spontaneous coronary artery dissection (SCAD). Despite the absence of obstructive disease, it carries substantial morbidity and mortality, underscoring the need for accurate aetiological characterisation and tailored therapy. Our aim is to review the contemporary evidence of the role of advanced imaging modalities—cardiac magnetic resonance imaging (CMR), optical coherence tomography (OCT), intravascular ultrasound (IVUS) and invasive functional testing—in the diagnosis, prognostic stratification, and therapeutic guidance of patients with MINOCA. CMR is the non-invasive reference standard for differentiating true ischaemic MINOCA from non-ischaemic mimics such as myocarditis and Takotsubo syndrome, reclassifying the working diagnosis in up to two-thirds of cases. OCT and IVUS provide intracoronary characterisation of culprit substrates that are invisible via angiography, particularly plaque rupture, erosion, intramural haematoma and SCAD, while acetylcholine and adenosine testing identify endothelium-dependent vasospasm and endothelium-independent microvascular dysfunction respectively. Coronary Computed Tomography Angiography (CCTA) could also play an additional role in the diagnosis of epicardial CAD. Each modality additionally carries independent prognostic value, with abnormal findings consistently linked to higher rates of major adverse cardiovascular events. The recently completed PROMISE trial provided the first randomised evidence that stratified, imaging-guided treatment might have some positive impact on angina status and quality of life compared with empirical standard care. In conclusion, advanced imaging has transformed MINOCA from a diagnosis of exclusion into a mechanism-based syndrome amenable to personalised therapy. Broader integration of these modalities into routine practice, supported by further randomised trials, is needed to optimise outcomes.

Anabolic–androgenic steroids (AASs) are synthetic derivatives of testosterone and are increasingly misused to enhance muscle growth and physical performance, particularly among athletes and recreational bodybuilders. Although AASs affect multiple organ systems, their severe and potentially life-threatening complications involve the cardiovascular system. This review summarizes current knowledge on the pathophysiological mechanisms and clinical manifestations of AAS-induced cardiomyopathy. Chronic supraphysiologic AAS use promotes cardiac injury and adverse cardiac remodeling via oxidative stress, androgen receptor overactivation, RAAS dysregulation, and pro-apoptotic signaling. These changes could lead to hypertension, dyslipidemia and atherosclerosis, myocardial fibrosis and hypertrophy, arrhythmias, heart failure, and kidney injury. Vascular dysfunction, increased arterial stiffness, and a prothrombotic state further compound the cardiovascular risks. Diagnostic approaches involve biomarker evaluation, echocardiography, and cardiac magnetic resonance imaging, revealing structural and functional cardiac abnormalities such as reduced ejection fraction, concentric hypertrophy, myocardial fibrosis, and impaired diastolic function. Although cessation of AAS use may lead to partial or complete reversal of cardiac dysfunction in some individuals, others may experience irreversible myocardial damage. The reversibility appears to depend on dosage, duration of exposure, and early intervention. This review explores the cardiovascular consequences of AAS use, with a focus on the mechanisms, diagnosis, and management of AAS-induced cardiomyopathy, and underlines the importance of education and early detection.

Right ventricular-pulmonary arterial (RV-PA) coupling describes the interaction between right ventricular contractility and pulmonary arterial afterload, offering a comprehensive assessment of right heart function. In the context of structural heart interventions such as transcatheter aortic valve implantation (TAVI), transcatheter edge-to-edge mitral repair (TEER), and transcatheter tricuspid therapies, RV-PA coupling has emerged as a powerful prognostic indicator. Impaired coupling, typically defined using echocardiographic surrogates such as the tricuspid annular plane systolic excursion (TAPSE)/pulmonary artery systolic pressure (PASP) ratio, is consistently associated with increased mortality and heart failure hospitalization. RV-PA coupling also demonstrates dynamic behavior, with potential for improvement following intervention-though persistent uncoupling portends worse outcomes. Despite its clinical promise, significant limitations exist. Commonly used non-invasive indices, while practical, only moderately correlate with gold-standard invasive pressure-volume loop assessments and are subject to measurement variability and lack of standardization. Furthermore, current surrogates do not distinguish between the underlying drivers of uncoupling-whether impaired contractility or increased afterload-each with distinct therapeutic implications. As structural heart interventions expand to broader patient populations, a more refined understanding of RV-PA coupling may enhance risk stratification, procedural planning, and long-term management. Future research should focus on standardizing assessment techniques and establishing evidence-based thresholds to support its routine clinical use.

Hypertension, characterized by elevated blood pressure levels, remains a global health concern due to its association with cardiovascular complications, notably thrombosis. Thrombosis, the formation of blood clots within blood vessels, poses a significant risk for myocardial infarction, stroke, and limb ischemia, leading to adverse patient outcomes. Understanding the pathophysiological mechanisms underlying thrombosis in hypertension is crucial for developing effective preventive and therapeutic strategies. Hypertension induces structural and functional alterations in the vasculature, endothelium, and platelets, creating a prothrombotic milieu. Endothelial dysfunction, increased platelet activation, and alterations in coagulation factors contribute to the heightened thrombotic risk observed in hypertensive individuals. Biomarkers associated with thrombotic events, such as mean platelet volume, D-Dimer, and fibrinogen offer valuable insights into the pathogenesis of thrombosis and may serve as prognostic indicators for cardiovascular events in hypertensive populations. Investigating the impact of antihypertensive treatment on thrombotic risk is essential, as these medications exert pleiotropic effects on the vasculature and hemostatic system. By elucidating the intricate interplay between hypertension and thrombosis, this review aims to enhance our understanding of cardiovascular risk in hypertensive individuals and identify novel therapeutic targets for preventing thrombotic complications.

Arterial hypertension is highly prevalent among individuals with chronic kidney disease (CKD), exhibiting a bidirectional association and playing a critical role in the progression of renal dysfunction. CKD affects approximately 10–12% of the global population and is often a common comorbidity in patients with true resistant hypertension. The sympathetic nervous system (SNS) plays a key role in the pathophysiological cascade of CKD-mediated hypertension. Current pharmacological therapies do not directly target SNS overactivity, highlighting the need for alternative approaches. Renal denervation (RDN), an interventional procedure that modulates both afferent and efferent renal nerve signaling, has emerged as a promising strategy for resistant hypertension with multiple pleiotropic benefits. Both preclinical and clinical trial data indicate that RDN is safe, with no significant deterioration of renal function reported in both early-stage CKD and end-stage renal disease (ESRD), as well as effective in reducing both office and ambulatory blood pressure in most studies. This review examines the pathophysiological basis for SNS overactivity in CKD, summarizes preclinical and clinical data on the safety and efficacy of RDN in this population, and discusses ongoing and future trials that may further clarify the role of RDN in CKD management and its long-term impact on renal and cardiovascular outcomes.

INTRODUCTION:Microvascular resistance reserve (MRR) is a novel indice for coronary microcirculation assessment, addressing limitations of coronary flow reserve (CFR) and index of microcirculatory resistance (IMR). Given its promising role in the future of coronary microvascular dysfunction assessment, we aimed to systematically review and meta-analyze available studies reporting its prognostic significance. METHODS:We performed a systematic search in 3 different databases (MEDLINE/PubMed, Web of Science and Scopus). After selecting all appropriate studies according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a random effect meta-analysis was performed. RESULTS:Our analysis, including 5 studies and a total of 1605 (453 abnormal MRR; 1152 normal MRR) patients, shows that patients with abnormal MRR are at significantly higher risk for cardiovascular death [Risk Ratio (RR): 4.88 95 % Confidence Interval (CI): 3.49-6.83], major adverse cardiovascular events (RR: 2.37; 95%CI: 1.52-3.70), myocardial infarction (RR: 1.93; 95%CI: 1.53-2.42) and heart failure hospitalizations (RR: 4.83; 95%CI: 1.59-14.70), in comparison to the normal MRR cohort. As expected, abnormal MRR was not associated with a significantly higher risk of future revascularizations, compared to normal controls (RR: 1.29; 95%CI: 0.52-3.19). CONCLUSION:This study shows the significant microcirculation-specific prognostic effect of MRR in both survival and adverse outcomes. Further data from large randomized studies, will delineate the clinical utility and prognostic effect of MRR in coronary microvascular dysfunction.

Cardiac amyloidosis (CA) often leads to heart failure (HF) with preserved left ventricular ejection fraction, while also affecting right ventricular (RV) function and its ability to adapt to changes in afterload. Right ventricular-pulmonary arterial (RV-PA) coupling is a crucial indicator of this property, with its prognostic importance been recently investigated in various cardiovascular diseases. The aim of this systematic review and meta-analysis is to investigate the prognostic significance of RV-PA coupling in patients with CA. We conducted a systematic literature search for studies assessing the prognostic role of RV-PA coupling in patients with CA. We recorded the method of RV-PA coupling assessment, the used cutoffs, patients’ age, sex, and follow-up duration. The outcomes of interest were all-cause mortality (ACM), cardiovascular mortality (CVM), hospitalization for HF (HHF), as well as combined endpoints (ACM+HHF, CVM+HHF) at maximal follow-up. We extracted the event rates for those endpoints according to RV-PA coupling, as defined by each study. Pooling of the risk ratios was conducted according to a random effects model. I2 was chosen as the measure of between-study heterogeneity, with values exceeding 50% being considered significant. We identified a total of 88 studies, of which 6 were ultimately selected for data extraction and inclusion in the meta-analysis after screening of title/abstract/full-text. All studies used the ratio between tricuspid annular plane systolic excursion (TAPSE) and pulmonary artery systolic pressure (PASP), with cutoffs ranging from 0.31 to 0.47mm/mmHg. Studies included elderly patients with mean age exceeding 70 years, with male sex predominance. The follow-up duration ranged from 6 to 23 months. According to the results of the meta-analysis, compared to the RV-PA coupling group, the presence of RV-PA uncoupling was associated with high rates of ACM (RR: 2.07, 95% CI: 1.50-2.85, p<0.0001), CVM (RR: 2.97, 95% CI: 1.60-5.53, p=0.0006), and HHF (RR: 2.69, 95% CI: 1.28-5.66, p=0.009) (Figure 1). We also observed an increased incidence of the combined endpoints (ACM+HHF, RR: 1.97, 95% CI: 1.29-3.00, p=0.002; CVM+HHF, RR: 2.18, 95% CI: 1.50-3.18) (Figure 1). There was evidence of moderate between-study heterogeneity in almost all the performed analyses. Our systematic review and meta-analysis highlight the prognostic impact of RV-PA uncoupling in patients with CA. RV-PA uncoupling through the TAPSE/PASP ratio was consistently associated with a higher risk of major adverse cardiovascular events, suggesting that it may serve as a valuable non-invasive marker for risk stratification in this high-risk population. However, the observed between-study heterogeneity underscores the need for further research to refine cutoff values and validate these findings in larger, prospective cohorts.Figure 1 Figure 2

Background Takotsubo Syndrome (TTS) is an increasingly recognized condition, initially perceived as benign, but now associated with considerable morbidity and mortality. Its pathophysiology remains elusive and despite advancements in understanding, management strategies remain inconsistent and lack support from randomized clinical trials. Aims This review aims to consolidate current evidence on the pathophysiology, diagnostic algorithms, treatment approaches, and prognosis of TTS, while highlighting the ongoing debates and challenges in its management. Methods A comprehensive review of recent literature was conducted, focusing on key studies, registries, and consensus guidelines. Results TTS is predominantly observed in postmenopausal women and is often triggered by emotional or physical stressors. The pathophysiology likely involves catecholamine surges, microvascular dysfunction, and inflammation. Diagnosis relies on imaging modalities like echocardiography and cardiac MRI, with the InterTAK criteria being the most widely accepted. Acute management focuses on stabilizing patients based on hemodynamic status, avoiding harmful interventions, and carefully selecting pharmacotherapy, despite mixed evidence for long-term benefit. Prognosis varies significantly, with worse outcomes associated with physical stress triggers, male gender, and comorbidities. Recurrence rates remain low but concerning, with inconsistent data regarding the effectiveness of the neuro-hormonal blockade medications and other therapies in preventing recurrence. Conclusion TTS poses significant clinical challenges due to its variable prognosis and lack of standardized treatment. Current management is largely symptomatic and supportive, with decisions tailored to individual risk profiles.