Sudden cardiac death after early-onset myocardial infarction. A multicentre longitudinal cohort study with 20 years' follow-up.

BACKGROUND: Sudden cardiac death (SCD) is a serious consequence of a myocardial infarction (MI), but identifying patients at risk of developing SCD remains a major clinical challenge especially in the case of juvenile MI. The aim of this study was to identify predictors of SCD after early-onset MI using long-term follow-up data relating to a large nationwide patient cohort. METHODS: The Italian Genetic Study on Early-onset MI enrolled 2,000 patients experiencing a first MI before the age of 45 years, who were followed up for a median of 19.9 years. Fine-Gray proportional hazard models were used to assess the associations between their clinical, demographic and index event data and the occurrence of SCD. RESULTS: SCD occurred in 195 patients, who were more frequently males, hypertensive and/or diabetic; had a history of previous thromboembolic events with a greater atherosclerotic burden; and had a lower left ventricular ejection fraction (LVEF) after the index event. Multivariable analysis showed that the independent predictors of SCD were diabetes, hypertension, previous thromboembolic events, higher Syntax score, and a lower LVEF. There was no clear evidence of the clustering of SCD events during follow-up. SCD was the first post-MI clinical event in 101 patients; the remaining 94 experienced SCD after a non-fatal MI or hospitalisation for coronary revascularisation. CONCLUSIONS: SCD frequently occurs during the 20 years after early-onset MI. The nature of the identified predictors and the absence of clustering suggests that the pathophysiological basis of SCD may be related to progressive coronary atherosclerosis.

Optimizing Management of Stable Angina: A Patient-Centered Approach Integrating Revascularization, Medical Therapy, and Lifestyle Interventions.

Angina pectoris may arise from obstructive coronary artery disease (CAD) or in the absence of significant CAD (ischemia with nonobstructed coronary arteries [INOCA]). Therapeutic strategies for patients with angina and obstructive CAD focus on reducing cardiovascular events and relieving symptoms, whereas in INOCA the focus shifts toward managing functional alterations of the coronary circulation. In obstructive CAD, coronary revascularization might improve angina status, although a significant percentage of patients present angina persistence or recurrence, suggesting the presence of functional mechanisms along with epicardial CAD. In patients with INOCA, performing a precise endotype diagnosis is crucial to allow a tailored therapy targeted toward the specific pathogenic mechanism. In this expert opinion paper, we review the evidence for the management of angina, highlighting the complementary role of coronary revascularization, optimal medical therapy, and lifestyle interventions and underscoring the importance of a personalized approach that targets the underlying pathobiology.

Angiographic and clinical impact of balloon inflation time in percutaneous coronary interventions with sirolimus-coated balloon: A subanalysis of the EASTBOURNE study.

INTRODUCTION: Percutaneous coronary intervention (PCI) with drug-coated balloon (DCB) is an attractive strategy for the treatment of obstructive coronary artery disease (CAD). The implantation technique strongly influences the outcome of DCB PCI: accurate and adequate lesion preparation, short delivery time and sufficient DCB inflation time are deemed crucial to warrant adequate drug transfer and mitigate the risk of immediate vessel recoil and flow-limiting dissections. However, the optimal DCB inflation time is unclear, current consensus documents suggesting 30-60 s based on Experts' opinion. However, clinical studies comparing the prognostic role of different inflation times are scarce and mainly involve paclitaxel-coated balloons. In this study we aimed to assess the impact of different inflation times in patients undergoing PCI with a sirolimus-coated balloon (SCB). METHODS: We conducted a post-hoc analysis of the prospective, multicenter, EASTBOURNE study, classified into two study groups according to balloon inflation time: long (>30 s) versus short (≤30 s). The primary endpoint was target lesion revascularization (TLR) at 24-month follow-up. Secondary clinical endpoints were major adverse clinical events (MACE), death, non-fatal myocardial infarction (MI), and BARC 2-5 bleedings. Furthermore, angiographic endpoints (the rate of bailout stenting and post-procedural TIMI flow <3) were also addressed. RESULTS: A total of 2289 lesions (2092 in the long inflation group, 197 in the short inflation group) were included in the analysis. Median balloon inflation time was 60 s in the long inflation and 30 s in the short inflation group. The two study groups experienced a similar rate of TLR [6.2 % in the short versus 6.3 % in the long inflation group, p = 1.00] as well MACE (p = 0.683), death (p = 0.102), non-fatal MI (p = 0.822), and BARC 2-5 bleedings (p = 0.252). These results were consistent when considering subpopulations with different target lesion phenotypes (in-stent restenosis, de-novo lesions, large and small vessels). Interesting, the rate of bailout stent implantation and post-procedural TIMI flow <3 was higher in the short SCB inflation time, as compared to the standard strategy. CONCLUSIONS: Short vs. long SCB inflation time is associated with a higher need of bailout stenting after PCI with SCB, with similar clinical outcomes at 24-month follow-up.

How to better prevent sudden cardiac death? Recent advances.

Sudden cardiac death (SCD) is a global public health problem. Despite the efforts of the scientific community, it is characterized by low survival (<10%). The strategies used to prevent this catastrophic event are divided into strategies aimed at the individual or population-level. Individuals known to be at high risk for SCD may be treated with medications, implantable cardioverter-defibrillators, catheter ablation, or temporary defibrillation devices. At community level, efforts are concentrated on the one hand on the prevention of ischemic heart disease as it constitutes more than 70% of cases of sudden mortality in the adult population, and on the other on the development of resuscitation and early defibrillation programs. Much still needs to be done to improve survival on the one hand by raising awareness among the population through training initiatives and on the other by optimizing and making available technologies more accessible.

Lessons from a geriatric clinical case from the 19th century: a bridge to modern geriatric medicine.

Count Neipperg (1775-1829), the morganatic husband of Maria Luigia of Habsburg, Napoleon's former wife, presented with typical heart failure symptoms and died of bilateral bronchopneumonia. Neipperg's case is an example of the conflict in the medical field, which led to the birth of modern evidence-based medicine (EBM), and although Neipperg died almost 200 years ago, his case presents the same critical issues that more complex geriatric patients face today. First, the attending physicians provided divergent opinions without reaching an agreement. For example, Francesco Rossi correctly diagnosed heart disease by evaluating the patient's signs and symptoms, a clinical approach that is an early example of modern EBM. By contrast, Giacomo Tommasini made a misdiagnosis based on the philosophical principles of John Brown's vitalist theory, as reworded by Giovanni Rasori. Second, Tommasini's medical report also includes evidence of the Geriatric 5Ms for older patient care, such as multi-complexity, multimorbidity, medication, mobility, and the mind. Moreover, both physicians considered "what matters most" for the patient and his family. Third, the Count's status and political role were identified as the social and structural determinants of health (SSDoH) and used to justify the exceptional intensity of the health care provided. Subsequently, the ante litteram application of EBM and a clinical evaluation based on Geriatrics 5Ms principles anticipate current multidisciplinary management focused on the patient rather than a single disease. The systematic revision of past clinical cases not examined before could open new windows in the dissemination of the geriatric methodology and discipline.

Polymer-free stents for percutaneous coronary intervention in diabetic patients: a systematic review and meta-analysis.

Aim: To compare the efficacy of polymer-free drug-eluting stents (PF-DES) versus other stents in diabetic patients with coronary artery disease undergoing percutaneous coronary interventions. Materials & methods: A systematic review and meta-analysis were performed to identify pertinent randomized controlled trials. The primary end point was the occurrence of target lesion failure. Results: Eight randomized controlled trials were included for a total of 4854 subjects. The PF-DES group experienced a trend in favor of a lower rate of target lesion failure (Incidence rate ratio = 0.91; p = 0.11) and a significantly lower rate of cardiac mortality, as compared with the control group (Incidence rate ratio = 0.82; p = 0.04). However, statistical significance was lost if bare-metal stent patients were excluded and a trend in favor of the PF-DES strategy was reported only for cardiac mortality. Conclusion: PF-DES could be a valuable strategy in diabetic patients with coronary artery disease undergoing percutaneous coronary interventions.

What is this summary about? Polymer-free drug-eluting stents (PF-DES) are a novel type of coronary stent with potential benefits in terms of chronic coronary inflammation. This is a comprehensive, up-to-date, systematic review and meta-analysis of randomized controlled trials comparing the efficacy of PF-DES versus other stents in diabetic patients with coronary artery disease undergoing percutaneous coronary intervention.What were the results? Patients treated with PF-DES experienced similar prognosis, with a trend toward better outcomes, as compared with conventional stents.What do the results mean? PF-DES could represent a novel and effective strategy for treating coronary artery disease in diabetic patients.

Effects of left bundle branch block on echocardiographic coronary flow assessment: A systematic review.

This systematic review investigates the diagnostic and prognostic utility of coronary flow reserve (CFR) assessment through echocardiography in patients with left bundle branch block (LBBB), a condition known to complicate the clinical evaluation of coronary artery disease (CAD). The literature search was performed on PubMed, EMBASE, Web of Science, Scopus, and Google Scholar, was guided by PRISMA standards up to March 2024, and yielded six observational studies that met inclusion criteria. These studies involved a diverse population of patients with LBBB, employing echocardiographic protocols to clarify the impact of LBBB on coronary flow dynamics. The findings emphasize the importance of CFR in stratifying cardiovascular risk and guiding clinical decision-making in patients with LBBB. Pooled results reveal that patients with LBBB and significant left anterior descending (LAD) artery stenosis exhibited a marked decrease in stress-peak diastolic velocity (MD = -19.03 [-23.58; -14.48] cm/s; p < .0001) and CFR (MD = -.60 [-.71; -.50]; p < .0001), compared to those without significant LAD lesions, suggesting the efficacy of stress echocardiography CFR assessment in the identification of clinically significant CAD among the LBBB population. This review highlights the clinical relevance of echocardiography CFR assessment as a noninvasive tool for evaluating CAD and stratifying risk in the presence of LBBB and underscores the need for standardized protocols in CFR measurement.

Impact of hyperaemic stenosis resistance on long-term outcomes of stable angina in the ILIAS Registry.

BACKGROUND: The hyperaemic stenosis resistance (HSR) index was introduced to provide a more comprehensive indicator of the haemodynamic severity of a coronary lesion. HSR combines both the pressure drop across a lesion and the flow through it. As such, HSR overcomes the limitations of the more traditional fractional flow reserve (FFR) or coronary flow reserve (CFR) indices. AIMS: We aimed to identify the diagnostic and prognostic value of HSR and evaluate the clinical implications. METHODS: Patients with chronic coronary syndromes (CCS) and obstructive coronary artery disease were selected from the multicentre ILIAS Registry. For this study, only patients with combined Doppler flow and pressure measurements were included. RESULTS: A total of 853 patients with 1,107 vessels were included. HSR more accurately identified the presence of inducible ischaemia compared to FFR and CFR (area under the curve 0.71 vs 0.66 and 0.62, respectively; p<0.005 for both). An abnormal HSR measurement was an independent and important predictor of target vessel failure at 5-year follow-up (hazard ratio 3.80, 95% confidence interval: 2.12-6.73; p<0.005). In vessels deferred from revascularisation, HSR seems to identify more accurately those vessels that may benefit from revascularisation rather than FFR and/or CFR. CONCLUSIONS: The present study affirms the theoretical advantages of the HSR index for the detection of ischaemia-Âinducing coronary lesions in a large CCS population. (Inclusive Invasive Physiological Assessment in Angina Syndromes Registry [ILIAS Registry], ClinicalTrials.gov: NCT04485234).

Coronary Microvascular Dysfunction: A Guide for Clinicians.

Dysfunction of the coronary microvasculature has become increasingly recognized as an important mechanism of myocardial ischemia in patients without obstructive coronary artery disease. The causes and management of coronary microvascular dysfunction remain poorly understood and are still largely based on extrapolation of epicardial coronary artery disease data. Quantification of myocardial blood flow and flow reserve have improved diagnosis, though important questions remain. In this review, we explain current understanding of the spectrum of pathophysiology of coronary microvascular dysfunction, summarize current diagnostic techniques to assess for coronary microvascular dysfunction, and appraise the limited data on management options specifically for patients with coronary microvascular dysfunction.

Cardiovascular Disease from Pathophysiology to Risk Estimation: Is Inflammation Estimated through Perivascular Attenuation on Computed Tomography the Key?

(1) Background: Systemic inflammation stands as a well-established risk factor for ischemic cardiovascular disease, as well as a contributing factor in the development of cardiac arrhythmias, notably atrial fibrillation. Furthermore, scientific studies have brought to light the pivotal role of localized vascular inflammation in the initiation, progression, and destabilization of coronary atherosclerotic disease. (2) Methods: We comprehensively review recent, yet robust, scientific evidence elucidating the use of perivascular adipose tissue attenuation measurement on computed tomography applied to key anatomical sites. Specifically, the investigation extends to the internal carotid artery, aorta, left atrium, and coronary arteries. (3) Conclusions: The examination of perivascular adipose tissue attenuation emerges as a non-invasive and indirect means of estimating localized perivascular inflammation. This measure is quantified in Hounsfield units, indicative of the inflammatory response elicited by dense adipose tissue near the vessel or the atrium. Particularly noteworthy is its potential utility in assessing inflammatory processes within the coronary arteries, evaluating coronary microvascular dysfunction, appraising conditions within the aorta and carotid arteries, and discerning inflammatory states within the atria, especially in patients with atrial fibrillation. The widespread applicability of perivascular adipose tissue attenuation measurement underscores its significance as a diagnostic tool with considerable potential for enhancing our understanding and management of cardiovascular diseases.

Effects of Static Meditation Practice on Blood Lipid Levels: A Systematic Review and Meta-Analysis.

This review aims to delineate the potential impact of static meditation practice on cholesterol and triglyceride levels. PubMed, EMBASE, Web of Science, Cochrane Library, and Google Scholar were systematically screened up until December 2023 to identify pertinent studies. After searching the scientific literature, 16 clinical studies (11 trials and 5 observational experiments) met the criteria for inclusion, involving a total of 1147 participants. In general, Ayurvedic-based meditation techniques were predominantly associated with lower total cholesterol levels, mindfulness-based techniques demonstrated benefits in both total cholesterol and triglyceride levels, and Eastern meditation techniques with spiritual origins were primarily linked to improved serum concentrations of HDL cholesterol. Study participants mostly engaged in meditation on a daily basis, often practicing it once or even twice a day, spanning a duration ranging from a few weeks to several months. The meta-analysis shows an association between meditation practice in healthy or sub-healthy adults and reduced cholesterol levels, with an average decrease of approximately -14 mg/dL (MD = -13.91 [-23.35; -4.47] mg/dL; p = 0.02), alongside favorable and even more pronounced impacts on triglyceride levels (MD = -32.56 [-48.44; -16.68] mg/dL; p < 0.01). In summary, regular engagement in static meditation practices can be associated with lower triglyceride and, to a lesser extent, cholesterol levels. Further studies on the topic are recommended to better investigate the relationship between meditation practice and physiological parameters.

Coronary Spasm Testing with Acetylcholine: A Powerful Tool for a Personalized Therapy of Coronary Vasomotor Disorders.

Coronary vasomotor disorders (CVD) are characterized by transient hypercontraction of coronary vascular smooth muscle cells, leading to hypercontraction of epicardial and/or microvascular coronary circulation. CVDs play a relevant role in the pathogenesis of ischemia, angina and myocardial infarction with non-obstructive coronary arteries. Invasive provocative testing with intracoronary Acetylcholine (ACh) administration is the gold standard tool for addressing CVD, providing relevant therapeutic and prognostic implications. However, safety concerns preclude the widespread incorporation of the ACh test into clinical practice. The purpose of this review is to shed light on the pathophysiology underlying CVD and on the clinical role of the ACh test, focusing on safety profile and prognostic implications. We will also discuss contemporary evidence on the management of CVD and the role of the ACh test in driving a personalized approach of patients with CVD.

Predicting the response to acetylcholine in ischemia or infarction with non-obstructive coronary arteries: The ABCD score.

BACKGROUND AND AIMS: Acetylcholine (ACh) provocation testing can detect vasomotor disorders in patients with ischemia and non-obstructed coronary arteries (INOCA) or myocardial infarction and non-obstructed coronary arteries (MINOCA). We aimed to derive and validate a simple risk score to predict a positive ACh test response. METHODS: We prospectively enrolled consecutive INOCA and MINOCA patients undergoing ACh provocation testing. Patients were split in two cohorts (derivation and validation) according to time of enrolment. The score was derived in 386 patients (derivation cohort) and then validated in 165 patients (validation cohort). RESULTS: 551 patients were enrolled, 371 (67.3%) INOCA and 180 (32.7%) MINOCA. ACh test was positive in 288 (52.3%) patients. MINOCA, myocardial bridge (MB), C-reactive protein (CRP) and dyslipidaemia were independent predictors of a positive ACh test in the derivation cohort. The ABCD (Acute presentation, Bridge, CRP, Dyslipidaemia) score was derived: 2 points were assigned to MINOCA, 3 to MB, 1 to elevated CRP and 1 to dyslipidaemia. The ABCD score accurately identified patients with a positive ACh test response with an AUC of 0.703 (CI 95% 0.652-0.754,p < 0.001) in the derivation cohort, and 0.705 (CI 95% 0.626-0.784, p < 0.001) in the validation cohort. In the whole population, an ABCD score ≥4 portended 94.3% risk of a positive ACh test and all patients with an ABCD score ≥6 presented a positive test. CONCLUSIONS: The ABCD score could avoid the need of ACh provocation testing in patients with a high score, reducing procedural risks, time, and costs, and allowing the implementation of a tailored treatment strategy. These results are hypothesis generating and further research involving larger cohorts and multicentre trials is needed to validate and refine the ABCD score.

Impact of sex on the assessment of the microvascular resistance reserve.

BACKGROUND: The microvascular resistance reserve (MRR) is an innovative index to assess the vasodilatory capacity of the coronary circulation while accounting for the presence of concomitant epicardial disease. The MRR has shown to be a valuable diagnostic and prognostic tool in the general coronary artery disease (CAD) population. However, considering the fundamental aspects of its assessment and the unique hemodynamic characteristics of women, it is crucial to provide additional considerations for evaluating the MRR specifically in women. AIM: The aim of this study was to assess the diagnostic and prognostic applicability of the MRR in women and assess the potential differences across different sexes. METHODS: From the ILIAS Registry, we enrolled all patients with a stable indication for invasive coronary angiography, ensuring complete physiological and follow-up data. We analyzed the diagnostic value by comparing differences between sexes and evaluated the prognostic value of the MRR specifically in women, comparing it to that in men. RESULTS: A total of 1494 patients were included of which 26% were women. The correlation between MRR and CFR was good and similar between women (r = 0.80, p < 0.005) and men (r = 0.81, p < 0.005). The MRR was an independent and important predictor of MACE in both women (HR 0.67, 0.47-0.96, p = 0.027) and men (HR 0.84, 0.74-0.95, p = 0.007). The optimal cut-off value for MRR in women was 2.8 and 3.2 in men. An abnormal MRR similarly predicted MACE at 5-year follow-up in both women and men. CONCLUSION: The MRR seems to be equally applicable in both women and men with stable coronary artery disease.

Prognostic role of coronary artery ectasia in patients with nonobstructive coronary artery disease.

AIMS: Coronary artery ectasia (CAE) has been linked to the occurrence of adverse events in patients with ischemia/angina and no obstructive coronary arteries (INOCA/ANOCA), while the relationship between CAE and myocardial infarction with nonobstructive coronary arteries (MINOCA) has been poorly investigated. In our study we aimed at assessing differences in clinical, angiographic and prognostic features among patients with CAE and MINOCA vs. INOCA/ANOCA presentation. METHODS: Patients with angiographic evidence of CAE were enrolled at the University Hospital of Parma and divided into MINOCA vs. INOCA/ANOCA presentation. Clinical and quantitative angiographic information was recorded and the incidence of major adverse cardiovascular events (MACE) was assessed at follow-up. RESULTS: We enrolled a total of 97 patients: 49 (50.5%) with MINOCA and 48 (49.5%) with INOCA/ANOCA presentation. The presentation with MINOCA was associated with a higher frequency of inflammatory diseases ( P  = 0.041), multivessel CAE ( P  = 0.030) and thrombolysis in myocardial infarction (TIMI) flow < 3 ( P  = 0.013). At a median follow-up of 38 months, patients with MINOCA had a significantly higher incidence of MACE compared with those with INOCA/ANOCA [8 (16.3%) vs. 2 (4.2%), P  = 0.045], mainly driven by a higher rate of nonfatal MI [5 (10.2%) vs. 0 (0.0%), P  = 0.023]. At multivariate Cox regression analysis, the presentation with MINOCA ( P  = 0.039) and the presence of TIMI flow <3 ( P  = 0.037) were independent predictors of MACE at follow-up. CONCLUSION: Among a cohort of patients with CAE and nonobstructive coronary artery disease, the presentation with MINOCA predicted a worse outcome.