Takotsubo syndrome (TTS) is an acute, usually reversible left ventricular dysfunction mimicking acute coronary syndrome without a culprit epicardial lesion. Once considered benign, it carries in-hospital mortality comparable to ST-segment elevation myocardial infarction. Coronary microvascular dysfunction (CMD) is frequently observed during the acute phase, but its relationship to TTS remains uncertain: it may be a predisposing substrate, a mediator of catecholamine-induced injury, or a consequence of edema, extravascular compression, altered loading conditions, and ventricular dysfunction, and human evidence shows association rather than mechanism. The index of microcirculatory resistance (IMR) is an established invasive measure of hyperemic microvascular resistance. In TTS, IMR is frequently elevated during the acute phase, and microvascular function appears to improve as left ventricular function recovers, although often incompletely. In a pooled analysis of individual patient data from 166 patients, acute-phase IMR was the only invasive index that remained associated with mortality after adjustment. The cutoff of 54 used in that analysis is an exploratory, hypothesis-generating prognostic threshold: derived within the same dataset, it requires external validation and should be distinguished from the diagnostic threshold of >= 25 used in CMD algorithms that have not been validated in acute conditions such as TTS. Wire-based IMR remains the gold standard; angiography-derived IMR is promising, but available software platforms remain investigational. This review examines proposed mechanisms, measurement methods and their validation, prognostic evidence, and management, and outlines a workflow for future research. We conclude that the clinical utility and optimal timing of invasive coronary function testing in TTS remain uncertain.
Background: Balancing thrombotic and bleeding risk in patients requiring direct oral anticoagulation (DOAC) after percutaneous coronary intervention (PCI) remains challenging. This study evaluated the safety of dual antithrombotic therapy with DOAC plus ticagrelor compared with DOAC plus clopidogrel in patients undergoing PCI for acute coronary syndrome or with high thrombotic risk. Methods: The ReDUAL PCI Real Life study was a Dutch, open-label, multicentre, registry-based randomized controlled trial within the Southeast Netherlands Heart Registry (ZON-HR), aiming to enrol 850 patients. Patients requiring DOAC were randomized 1:1 to DOAC plus ticagrelor or DOAC plus clopidogrel after PCI. The primary endpoint was any bleeding (BARC >= 2) at 1 year. Secondary endpoints included major adverse cardiac and cerebrovascular events (MACCE), and net adverse clinical events (NACE: MACCE plus major bleeding). Outcomes were compared with a non-randomized ZON-HR cohort eligible for inclusion. Results: The study was terminated prematurely due to slow recruitment, with 109 patients randomized (53 ticagrelor, 56 clopidogrel). Overall bleeding rates were similar between ticagrelor and clopidogrel (13.2% vs 14.3%). Major bleeding (9.4% vs 1.8%), MACCE (13.2% vs 5.4%), and NACE (20.8% vs 7.1%) occurred more frequently with ticagrelor, without statistical significance. In 397 eligible non-randomized clopidogrel-treated patients, major bleeding rate was 3.4%, MACCE occurred in 12.5% and NACE in 14.5%. Conclusions: In patients undergoing PCI requiring oral anticoagulation, DOAC plus ticagrelor showed similar overall bleeding but numerical increase in major bleeding without apparent ischemic benefit compared with DOAC plus clopidogrel. This prematurely terminated study was underpowered, limiting abilities to draw definitive conclusions.
Background: Patients with Angina and unobstructed coronary arteries (ANOCA) frequently suffer from coronary spasm. Intracoronary provocative testing may reveal microvascular and/or epicardial spasm. However, the relationship of these two spasm types has not been investigated systematically. Methods: We enrolled 142 ANOCA patients (mean age 63 years, 44% female) in whom intracoronary acetylcholine testing demonstrated epicardial spasm at the highest acetylcholine dose (i. e. 200 mu g) in the left coronary artery according to the COVADIS criteria. In all patients, demographic data, cardiovascular risk factors and procedural data were recorded. The latter included symptoms and/or ischemic ECG shifts during lower acetylcholine doses. This enabled diagnosis of micro-vascular spasm before documentation of epicardial spasm. Results: 49 out of 142 patients (35%) had microvascular spasm before documentation of epicardial spasm. Thirty-one patients (22%) had an uneventful test and in 62 (43%) the acetylcholine test was inconclusive. Statistical analysis revealed no significant differences between patients with and without microvascular spasm regarding cardiovascular risk factors. However, patients with microvascular spasm were significantly more often female (55% vs. 29%, p = 0.037). Multivariable analysis revealed female sex as significant predictor for the occurrence of microvascular spasm (OR 3.0, 95% CI 1.15-7.80, p = 0.021). Conclusion: In patients with epicardial spasm microvascular spasm at lower acetylcholine doses can be diagnosed in 35% of ANOCA patients. Independent of cardiovascular risk factors women are affected by this scenario three times more often than men. Our results underline the importance of the coronary microcirculation and sex-specific differences in the pathophysiology of coronary spasm.
BACKGROUND Patients with severe tricuspid regurgitation (TR) frequently present with advanced right heart failure (RHF), commonly attributed to delayed referral for intervention. Whether this reflects delayed referral or the stage at which severe TR is first documented remains uncertain. METHODS We retrospectively analyzed 625 consecutive patients with a first echocardiographic diagnosis of severe TR. RHF severity was classified using a validated hierarchical staging system (Stages 1-4). In a subgroup of 310 patients with a previous echocardiogram documenting non-severe TR, RHF stage was retrospectively assessed before severe TR was first documented. Two-year all-cause mortality was evaluated. RESULTS At first documentation of severe TR, 66.4% of patients were classified as Stage 3 and 17.3% as Stage 4, whereas only 16.3% were in Stages 1-2. Functional TR accounted for 85% of cases. RHF stage was associated with progressively higher TRI-SCORE and two-year mortality. Among patients with prior non-severe TR, 78% were already in Stage 3-4 before severe TR was first documented, whereas only 7% had reached Stage 4. CONCLUSIONS Severe TR was predominantly diagnosed in patients with stage 3-4 RHF. Higher RHF stages were already present in most patients before severe TR was first documented. These findings suggest that delayed referral alone may not fully explain the advanced clinical profile of severe TR and that eligibility for guideline-directed intervention frequently coincides with an already advanced stage of disease.
Background: QT interval corrected for heart rate (QTc) is important. Appropriate reference ranges support ECG interpretation, but data for Eastern European children remain limited. We aimed to derive age- and sex-stratified QTc reference ranges, estimate proportions exceeding cut-offs, and compare results with normative datasets. Methods: 12-lead ECGs from 22,335 children aged 6-18 years were obtained through the CARDIOPED screening programme in northwestern Transylvania, Romania. QTc was calculated using Bazett's formula. Age- and sexstratified percentile curves (P2.5-P97.5) were derived using spline regression. Correlations with anthropometric variables and proportions exceeding QTc cut-offs of 440, 460, and 480 ms were assessed. Results were compared with the Davignon, Rijnbeek, Saarel, Bratincsak, and Mason datasets. Results: Overall median QTc was 408.2 ms in males and 409.9 ms in females. Upper reference limits (P97.5) were 451.4 ms and 457.0 ms, respectively. The sex difference increased from 2.6 ms in the 6-12-year group to 5.7 ms in the 12-18-year group. Obesity and anthropometric variables showed weak, non-significant correlations with QTc. Values were closely aligned with Rijnbeek et al. QTc exceeded 440 ms in 6.0% of males and 460 ms in 1.2% of females; 14 children (0.06%) had a single screening QTc measurement >= 480 ms. Conclusions: QTc reference ranges in this Eastern European cohort were consistent with European paediatric normative data. Upper reference limits were approximately 450 ms in males and 460 ms in females. Proportions exceeding cut-offs describe cohort distributions, not diagnostic false-positive rates. Percentiles are statistical reference limits rather than validated clinical decision or diagnostic thresholds.
