The aim of this study was to elucidate cardiovascular prescriber access, uptake, and attitudes toward CYP2C19 and CYP2D6 genetic testing to guide prescribing of commonly used medications such as clopidogrel, antiarrhythmics, proton pump inhibitors, and antidepressants. A survey, designed in collaboration with the European Society of Cardiology (ESC) WG on Cardiovascular Pharmacotherapy and external experts was disseminated to ESC members using SurveyMonkey. 265 prescribers from 68 countries participated. Most respondents thought testing would be beneficial, though CYP2C19 testing was perceived as more beneficial (73%) and desirable than CYP2D6 (61%). Access to CYP2C19 testing was more common (30%) than CYP2D6 testing (19%), but mostly outside of public funded health systems. Uptake in those who had access was higher for CYP2C19 (67%), than for CYP2D6 (33%). Confidence in interpreting results to prescribe was also higher with CYP2C19 (69%) than with CYP2D6 (53%), but most respondents wanted information prior to prescribing. One third of respondents highlighted the need for a turnaround time that matched their clinical practice. Unsolicited Pharmacogenomic (PGx) information from a patient was uncommon, but most prescribers acted on the information. A minority of respondents had undertaken PGx testing themselves, but most wanted testing for relevant medications. Respondents' experiences as patients made them more likely to believe that PGx testing was warranted. A minority ( ~ 15%) were aware of either local prescriber guidance or patient information materials regarding PGx testing. Prescribers want access to pharmacogenomics data regarding CYP2C19 and CYP2D6 for prescribing cardiovascular medicines. However, there are barriers which hamper implementation. Prescribers lived experience with medication use as patients impacted their views of PGx. 265 prescribers responded to the ESC survey from 68 countries. Most prescribers wanted access to pharmacogenomic testing for CYP2C19 and CYP2D6 for their patients and for themselves. Though most prescribers thought these pharmacogenomic tests would be useful and could improve the risk/benefit profile of relevant medications, prescribers responded more positively to CYP2C19 compared with CYP2D6 testing. Guidance and information for both prescribers and patients were lacking.

Myocardial infarction (MI) is defined pathologically as myocardial cell death resulting from prolonged ischaemia. The clinical definition of this pathological process relies on clinical evidence of myocardial ischaemia and biomarker evidence of myocardial cell death. Cardiac troponins are the standard clinical biomarker for assessing cardiac cell death. Within the framework of the universal definition of myocardial infarction (UDMI), the definition of acute MI aims to guide clinicians to accurately diagnose and classify acute MI, and distinguish acute MI from other forms of myocardial injury in daily practice. In the latest (Fourth) UDMI, a major effort has been made to providing: (i) a stratified pathophysiology-informed framework for the classification of different MI types and (ii) an overview of the factors that should be considered for distinguishing MI from non-ischaemic myocardial injury. The development and implementation of the UDMI in its various iterations has intended to comprehensively define MI and not to provide an MI management guideline. It has resulted in major achievements. However, significant reservations have emerged among different stakeholders (Graphical Abstract) which form the basis of this 'Great Debate' manuscript.

Acute myocardial ischaemic syndromes frequently arise from rupture or erosion of non-flow-limiting vulnerable plaques. Despite major advances in lipid-lowering and anti-inflammatory therapies, a substantial residual cardiovascular risk persists under optimal medical therapy, driving interest in preventive percutaneous coronary intervention (PCI) to stabilize these high-risk lesions. Contemporary intracoronary imaging techniques, including intravascular ultrasound, optical coherence tomography, and near-infrared spectroscopy, can identify plaques at greatest risk of rupture, and preventive PCI, as demonstrated in the PREVENT trial, may reduce composite outcomes of cardiac death, myocardial infarction, revascularization, and unstable angina compared with medical therapy alone. Sealing such plaques may prevent future acute coronary events, particularly in high-risk patients with multivessel disease. However, these benefits were driven mainly by softer endpoints observed in an open-label design, and were not accompanied by significant reductions in mortality or hard outcomes. Concerns remain regarding the procedural risks and cost-effectiveness of preventive PCI, and the impact of novel and more intensive lipid-lowering therapies in this clinical setting has not been adequately explored. Although preventive PCI represents an intriguing paradigm shift that challenges physiology-guided treatment strategies, further studies are needed to confirm its safety, durability, and incremental value over contemporary medical therapy. This Great Debate examines whether preventive PCI should be considered the default management strategy for non-flow-limiting vulnerable plaques.

Exercise treadmill testing measures functional capacity and inducible myocardial ischemia and has historically served as an endpoint in phase 2 trials. The Precision Medicine with Zibotentan in Microvascular Angina trial evaluated the selective endothelin-A receptor antagonist zibotentan as a potential disease-modifying therapy for microvascular angina. The trial had a randomized, double-blind, cross-over design and the primary outcome was exercise duration. Compared with placebo, zibotentan at a dose of 10-mg daily for 12-weeks did not improve exercise duration or angina symptoms. In this prespecified analysis, exercise duration was compared across four sequential study visits and the factors associated with within-trial changes were evaluated. Exercise test duration increased progressively in all participants during sequential trial phases, independent of treatment with either zibotentan or placebo. This improvement in exercise duration was associated with female sex (interaction p-value = .0213; effect estimate [95% confidence interval]) 34.95 [13.99, 55.78] seconds, P = .002). In conclusion, the exercise test has limitations as an objective endpoint of efficacy in randomized trials. PRIZE; https://clinicaltrials.gov/study/NCT04097314 Clinicaltrials.gov Registration: NCT04097314.

Abstract Persistent cardiac symptoms are common in post-COVID syndrome, even without structural heart disease. Evidence implicates immune dysregulation, endothelial dysfunction and low-grade cardiovascular inflammation. Yet no targeted treatment exists. Myoflame-19 is a multicenter, double-blind clinical trial of 279 participants with inflammatory cardiac involvement defined by cardiovascular magnetic resonance, randomized 1:1 to losartan plus prednisolone ( n = 139 ) or matching placebos ( n = 140 ) for 16 weeks. The modified intention-to-treat population comprised 124 and 122 participants. The primary endpoint, change in left ventricular (LV) ejection fraction, was neutral: between-group difference 0.74 percentage points (pp), 95%CI −0.14 to 1.62, p = 0.10, unpaired t-test; supportive baseline-adjusted ANCOVA 0.99, 95%CI 0.15-1.83, p = 0.021. Among prespecified secondary endpoints, several symptom and imaging measures showed numerical differences favoring intervention, including Average Symptom Score components (modified Canadian Chest Pain Scale −4.8 pp, 95%CI −17.3 to 7.6; NYHA class −8.1 pp, −20.6 to 4.3; Long COVID symptom burden −7.7 pp, −18.9 to 3.6), native T1 and T2 values (native T1 −2.46 ms, −8.35 to 3.42; native T2 −0.31 ms, −1.16 to 0.53), and LV end-diastolic volume ( + 1.45 ml/m², −0.09 to 3.00); however, confidence intervals included the null value and these findings should be regarded as hypothesis-generating.Treatment was safe and well-tolerated. These findings indicate a neutral treatment effect on the primary endpoint. They inform targeted immunomodulation and design of future trials in post-COVID syndrome and inflammatory cardiac involvement. Trial registration: EudraCT 2022-001682-12; NCT05619653.

The prevalence of frailty and its effect on cardiovascular outcomes is increasing on a global scale. Pharmacotherapies for cardiovascular diseases in older people with frailty present unique challenges that require a comprehensive and individualized approach. In this Review, we provide a general overview of these challenges, followed by an in-depth discussion of the problems inherent in applying standard approaches to cardiovascular care in this population. Specifically, we consider blood pressure control, glucose lowering in patients with type 2 diabetes mellitus, lipid lowering, antiplatelet therapies, direct oral anticoagulants for stroke prevention in atrial fibrillation, and the treatment of heart failure. Although the reduction in cardiovascular events in older individuals with frailty is crucial, the potentially increased risk of adverse effects with the use of cardiovascular medications must be carefully considered. Treatment targets and the choice of drug for these patients should be based on their overall health status and personal goals of care. Frailty is common in older individuals, but can occur independently of advanced age, multimorbidity or disability. In this Review, Nguyen and colleagues draw on evidence from clinical guidelines and randomized controlled trials to provide an in-depth discussion of the unique challenges associated with cardiovascular pharmacotherapy in older patients with frailty.

Coronary artery spasm can be life-threatening. Clinically significant complications include myocardial infarction, ventricular arrhythmias, and sudden cardiac arrest. Although challenging to diagnose, new international guidelines have been published to guide the diagnosis of coronary artery spasm when this is the suspected cause of cardiac arrest. The aim of this review is to consider existing knowledge for the diagnosis and management of coronary artery spasm in survivors of sudden cardiac arrest. Twenty-seven original research articles (written in English) involving a total of 1541 survivors of sudden cardiac arrest associated with coronary artery spasm form the basis of this review. Most cohorts included >75% male participants with a mean age range of 45-63 years. A positive family history or coronary risk factors of coronary artery disease are not commonly found, albeit many survivors are smokers (ranged 17-100% across cohorts). Provocative testing for coronary spasm was reported in 25 of the evaluated papers, but the indications for testing were inconsistently specified. A high recurrence rate (up to 45%) of life-threatening ventricular arrhythmias was reported, and implantable cardioverter-defibrillator placement varied markedly. In conclusion, diagnosing coronary artery spasm as a cause of sudden cardiac arrest is challenging. The pathophysiological understanding is limited. Knowledge gaps include the incidence and prevalence, as well as the usefulness of provocative testing in survivors. More data are needed regarding patient risk stratification, indications for implantable cardioverter-defibrillator insertion, and optimal pharmacological therapy.

Despite recent advances in cardiovascular pharmacotherapy, prevention and treatment of many cardiovascular diseases remain limited with a clear need for more effective and safer pharmacological strategies. Here, we summarize the most relevant advances in cardiovascular pharmacotherapy in 2025, including the approval of four new drugs (aficamten, etripamil, lerodalcibep, and plozasiran), the label expansions for five already approved drugs, and the results of major randomized clinical trials with already approved drugs, including those that met the prespecified primary endpoints (positive trials) representing new pharmacological options for cardiovascular diseases, those with neutral or negative results, which did not confirm the primary endpoints and the withdrawal from the US market of Andexanet-alfa for safety concerns. Finally, we present the most promising experimental cardiovascular drugs currently being investigated in ongoing Phase 2 and 3 clinical trials.

ObjetivoEl objetivo del presente estudio es el de determinar si los nitratos de accion rapida tienen efectos deletereos en la respuesta a la ergometria y/o los sintomas de la vida diaria en pacientes con dolor toracico y coronariografia normal. AntecedentesLa utilidad de los nitratos en pacientes con dolor toracico y arterias coronarias angiograficamente normales es motivo de controversia. Mientras que en los grander estudios observacionales, los nitratos son eficaces en aproximadamente el 50% de los pacientes con dolor toracico y coronariografia normal, los estudios basados en la respuesta a la prueba de esfuerzo sugieren que este tratamiento podria ser no solo ineficaz, sino incluso deletereo. Debido a los resultados de estos trabajos, muchos de los pacientes son excluidos sistematicamente del tratamiento con nitratos. Material y metodo Se estudiaron dos grupos de pacientes. En el primer grupo se incluyeron 22 pacientes consecutivos con angina tipica de esfuerzo, ergometria positiva y arterias coronarias angiograficamente normales. Todos los pacientes de este grupo realizaron dos pruebas de esfuerzo en cinta rodante: la primera sin medicacion antianginosa y la segunda, 5 minutos despues de la administracion de 400 jig de nitroglicerina sublingual. En el segundo grupo se incluyeron los 22 pacientes del primer grupo y otros 55 con dolor toracico y arterias coronarias angiograficamente normales, que fueron reclutados durante el mismo periodo. Todos los pacientes recibieron tratamiento con nitroglicerina sublingual (comprimidos de 400 pg) a demanda, durante un mes. Asimismo, todos los pacientes completaron un cuestionario estandarizado, referente a los efectos de los nitratos sublinguales, sobre los episodios de angina que se presentaron durante las actividades de la vida diaria y los efectos adversos de la medicacion. ResultadosComparativamente con los resultados en situacion basal, la administracion de nitratos sublinguales incremento en forma significativa tanto el tiempo hasta la aparicion de la angina (p = 0,04) como el tiempo hasta el descenso de 1 mm del segmento ST (p = 0,03) durante la ergometria. De los 77 pacientes incluidos en la segunda parte del estudio, 51 (66%) refirieron que los nitratos sublinguales habian sido eficaces para el alivio del dolor toracico, el cual desaparecia en el termino de 1 a 5 minutos. Ningun paciente refirio exacerbacion de su dolor toracico, ni ningun otro efecto deletereo sobre la funcion cardiovascular, asociado con la administracion del farmaco. Quince pacientes (24%) suspendieron la administracion de nitratos sublinguales debido, sobre todo, a la presencia de cefalea. ConclusionesLos nitratos sublinguales mejoran la tolerancia al ejercicio en una proporcion considerable de pacientes con dolor toracico y arterias coronarias angiograficamente normales. Durante el seguimiento no se encontro que estos agentes tuvieran efectos deletereos sobre el dolor toracico.

Coronary artery disease is one of the leading causes of mortality worldwide. While early identification and treatment of major cardiovascular risk factors are crucial, recent data suggest the possibility of non-invasively detecting early stages of coronary atherosclerosis and potentially stabilizing or even reversing the burden of atherosclerosis with innovative and existing treatments. Moreover, therapies from lipid-lowering to anti-inflammatory drugs were recently demonstrated to influence atherosclerosis progression and potentially lead to different grades of plaque regression. The present is Part 1 of a scientific consensus document divided into two separate manuscripts. This first part provides an up-to-date scientific statement on the pathophysiology mechanism of atherosclerosis progression and regression and on the role of invasive and non-invasive imaging techniques in evaluating and quantifying plaque.

The diagnosis of refractory angina has conventionally been limited to patients with angina and ischaemia secondary to obstructive atherosclerotic epicardial coronary disease who experience persistent symptoms despite optimal pharmacological and revascularization therapies. It is now well-established that angina may also be caused by ischaemia resulting from coronary microcirculatory disorders, coronary vasospasm, and bridging in the absence of obstructive epicardial coronary disease or after "successful" revascularization. This increasingly prevalent and symptomatic group of patients, with both angina and demonstrable ischaemia, have been excluded from the conventional definition of refractory angina. In patients with obstructive epicardial coronary disease, disturbed microcirculatory and vasomotor function, amongst other ischaemic mechanisms, may account for continuing symptoms despite revascularization. Under-recognition of these mechanisms results in inadequate treatment and symptom persistence. In this review, a redefinition of refractory angina is proposed to include the full spectrum of patients experiencing persistent angina despite current maximal guideline-directed medical and revascularization therapies. Systematic approaches for comprehensive investigation are suggested to identify underlying mechanisms of ischaemia and stratify treatments accordingly. The complex needs of patients with refractory angina are likely best addressed by an inter-disciplinary Angina Heart Team with the aim of improving patient symptoms, quality of life, and clinical outcomes.

Heart failure (HF) and atrial fibrillation (AF) are major global health challenges with rising prevalence and significant morbidity, mortality, and healthcare burden. Despite advances in HF management, AF remains a critical comorbidity that worsens outcomes and requires ad hoc treatment strategies, increasing the risk of non-adherence and side effects. While rhythm control strategies in AF have gained attention for their prognostic benefits in HF, the pharmacological treatment of HF in patients with AF, including the benefit of rhythm versus rate control, remains underexplored. The relationship between HF and AF lacks sufficient evidence and targeted research to assess the optimal treatment strategies. This narrative review critically examines current HF pharmacotherapy in the context of AF, focusing on the four cornerstone treatments and modifiers of prognosis for HF with reduced ejection fraction: beta-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/sacubitril-valsartan, aldosterone antagonists, and sodium–glucose co-transporter 2 inhibitors. Although these therapies are well-established in HF patients, their efficacy in patients with concomitant AF requires further prospective investigation. The unique challenges posed by AF, including arrhythmia-induced remodelling and cardiomyopathy, necessitate a more individually tailored treatment. We also highlight critical knowledge gaps and the need for dedicated clinical trials specifically assessing HF therapies in AF subgroups, such as paroxysmal, long-standing persistent and permanent AF, and the benefit of heart rate and rhythm control strategies. The future of precision medicine in HF-AF management lies in bridging these evidence gaps through targeted research and interdisciplinary collaboration.

This review aims to examine the evidence on the benefits and risks of lipid-lowering drugs in patients with liver disease. Elevated liver enzyme levels often lead to cautious discontinuation of these drugs, potentially withholding from patients their benefit in reducing cardiovascular disease morbidity and mortality. Using a literature search of PubMed, we examine the efficacy and safety profiles of various lipid-lowering agents, including statins, ezetimibe, bempedoic acid, PCSK9 inhibitors, fibrates, and icosapent ethyl, focusing particularly on their potential side effects related to liver health. A major challenge in the assessment of drug-induced hepatotoxicity is the fact that it relies heavily on case reports rather than real-world evidence. There is currently a lack of robust evidence on lipid-lowering therapy in people with pre-existing liver disease. Nevertheless, we have attempted to summarize the available data for all the drugs mentioned in order to provide guidance for the treatment of patients with liver dysfunction. This review highlights the need for further research to optimize treatment strategies for patients with coexisting liver and cardiovascular disease.

BACKGROUND:Timing of invasive coronary angiography in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) remains controversial. Angiographic risk and, hence, myocardium at risk are not necessarily considered in currently used non-ST elevation myocardial infarction management algorithms. The aim of this study was to assess the diagnostic performance of the SAVE score in NSTE-ACS patients to noninvasively identify patients with high-risk angiographic risk who might benefit from an early invasive strategy. METHODS:We prospectively assessed 950 consecutive patients admitted to five different hospitals with a diagnosis of NSTE-ACS, 598 (491 male, mean age 63 ± 12 years) of whom were risk-stratified according to the SAVE risk score. The primary endpoint was the identification of high-risk angiographic features. RESULTS:High-risk angiographic features were observed in 347 (58%) (292 male/55 female). SAVE score was significantly higher in patients in the high-risk angiography group compared with patients without high-risk features [6 (4.5-8) ± vs. 4 (2-5.5); P  < 0.001]. Using the proposed risk score, 79% (275 out of 347 patients) were correctly identified as having a high angiographic risk, and 58% (145 out of 251 patients with low-risk angiographic features) were also correctly identified by the SAVE score. CONCLUSIONS:The SAVE score adequately identified patients with high angiographic risk who may benefit from early invasive management strategies.

IntroducciónLa presencia de diferentes grupos de riesgo en el síndrome coronario agudo sin elevación del segmento ST (SCASEST) lleva a la búsqueda de nuevas herramientas para realizar un diagnóstico y estratificación pronóstica precoces. Así, se ha mostrado que el intervalo QT corregido prolongado es un marcador independiente de riesgo en el SCASEST con cambios isquémicos agudos o sin ellos, no obstante, existen pocos datos sobre su relación con otras variables de reconocido valor pronóstico como las troponinas cardíacas. ObjetivoEvaluar la correlación entre el intervalo QT corregido prolongado y la troponina T cardíaca. Material y métodosSe incluyeron prospectivamente 106 pacientes. Se midió el intervalo QT corregido en el ECG de ingreso y a las 6, 12, 18, 24 y 48 horas. El punto de corte con mejor sensibilidad y especificidad para predecir eventos clínicos mayores fue de ≥ 0,458 seg. Se efectuó la determinación de troponina T cardíaca y se consideró positivo el valor ≥ 0,04 ng/ml. Los eventos clínicos mayores observados hasta los 30 días del alta fueron muerte de causa cardíaca, infarto de miocardio no mortal y angina recurrente, que constituyeron el punto final combinado. Se dividió a los pacientes en dos grupos según la presencia (grupo A) o la ausencia (grupo B) de estos eventos. Se correlacionaron los valores del intervalo QT corregido de admisión y máximo con los de troponina T cardíaca de cada grupo. Se aplicó análisis multivariado de regresión logística para identificar predictores independientes de eventos clínicos mayores. ResultadosEl coeficiente de correlación del intervalo QT corregido máximo con la troponina T cardíaca fue de 0,38 (p<0,001), y el intervalo QT corregido máximo ≥ 0,458 seg tuvo valor pronóstico independiente para eventos clínicos mayores [OR=4,1 (IC 95% 1,7-11,2); p=0,002] y valor predictivo negativo del 80,8%. ConclusionesEn pacientes con SCASEST, el intervalo QT corregido máximo se correlacionó con los niveles de troponina y fue predictor independiente de riesgo.

How to cite this article: Kaski JC. Consensus document on MINOCA. A turning point in the diagnosis and treatment of an intriguing condition. Rev Argent Cardiol 2021;89:469-471 http://dx.doi.org/10.7775/rac.v89.i6.20455