Characteristics of patients with recurrent acute myocardial infarction after MINOCA.

BACKGROUND: Myocardial infarction (MI) with non-obstructed coronary arteries (MINOCA) is an increasingly recognized condition with challenging management. Some MINOCA patients ultimately experience recurrent acute MI (re-AMI) during follow-up; however, clinical and angiographic factors predisposing to re-AMI are still poorly defined. METHODS: In this retrospective multicenter cohort study we enrolled consecutive patients fulfilling diagnostic criteria of MINOCA according to the IV universal definition of myocardial infarction; characteristics of patients experiencing re-AMI during the follow-up were compared to a group of MINOCA patients without re-AMI. RESULTS: 54 patients (mean age 66 ± 13) experienced a subsequent re-AMI after MINOCA and follow-up was available in 44 (81%). Compared to MINOCA patients without re-AMI (n = 695), on first invasive coronary angiography (ICA) MINOCA patients with re-AMI showed less frequent angiographically normal coronaries (37 versus 53%, p = 0.032) and had a higher prevalence of atherosclerosis involving 3 vessels or left main stem (17% versus 8%, p = 0.049). Twenty-four patients (44%) with re-AMI underwent a new ICA: 25% had normal coronary arteries, 12.5% had mild luminal irregularities (<30%), 20.8% had moderate coronary atherosclerosis (30-49%), and 41.7% showed obstructive coronary atherosclerosis (≥50% stenosis). Among patients undergoing new ICA, atherosclerosis progression was observed in 11 (45.8%), 37.5% received revascularization, only 4.5% had low-density lipoprotein cholesterol (LDL_C) under 55 mg/dL and 33% experienced a new cardiovascular disease (CVD) event (death, AMI, heart failure, stroke) at subsequent follow-up. CONCLUSIONS: In the present study, only a minority of MINOCA patients with re-AMI underwent a repeated ICA, nearly one out of two showed atherosclerosis progression, often requiring revascularization. Recommended LDL-C levels were achieved only in a minority of the cases, indicating a possible underestimation of CVD risk in this population.

Worldwide impact of COVID-19 on hospital admissions for non-ST-elevation acute coronary syndromes (NSTACS): a systematic review with meta-analysis of 553,038 cases.

BACKGROUND: How COVID-19 impacted non-ST-segment elevation acute coronary syndromes (NSTACS) is object of controversial reports. AIM: To systematically review studies reporting NSTACS hospitalizations during COVID-19 pandemic, and analyze whether differences in COVID-19 epidemiology, methodology of report, or public health-related factors could contribute to discrepant findings. METHODS: Comprehensive search (MedLine, Embase, Scopus, Web-of-Science, Cochrane Register), of studies reporting NSTACS hospitalizations during COVID-19 pandemic compared with a reference period, following Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Data were independently extracted by multiple investigators and pooled using a random-effects model. Health-related metrics were from publicly available sources, and analyzed through multiple meta-regression modelling. RESULTS: We retrieved 102 articles (553 038 NSTACS cases, 40 countries). During peak COVID-19 pandemic, overall Incidence Rate-Ratio (IRR) of NSTACS hospitalizations over reference period decreased (0.70, 95% CI 0.66-0.75; p < 0.00001). Significant heterogeneity was detected among studies (I2= 98%; p < 0.00001). Importantly, wide variations were observed among, and within, countries. No significant differences were observed by study quality, whereas comparing different periods within 2020 resulted in greater decrease ((IRR: 0.61; CI: 0.53-0.71) than comparing 2020 vs previous years (IRR: 0.74; CI 0.69-0.79). Among many variables, major predictors of heterogeneity were: Sars-Cov-2 reproduction rate/country, number of hospitals queried, reference period length; country stringency index and socio-economical indicators did not significantly contribute. CONCLUSIONS: During COVID-19 pandemic NSTACS hospitalizations decreased significantly worldwide. However, substantial heterogeneity emerged among countries, and within the same country. Factors linked to public health management, but also to methodologies to collect results may have contributed to this heterogeneity. Trial registration: The protocol was registered in PROSPERO International Prospective Register of Systematic Reviews (ID: CRD42022308159).

Myocardial infarction with nonobstructive coronary arteries: from pathophysiology to therapeutic strategies.

Myocardial infarction with nonobstructive coronary arteries (MINOCA) is a heterogeneous group of clinical entities characterized by clinical evidence of acute myocardial infarction (AMI) with normal or near-normal coronary arteries on coronary angiography (stenosis < 50%) and without an over the alternative diagnosis for the acute presentation. Its prevalence ranges from 6% to 11% among all patients with AMI, with a predominance of young, nonwhite females with fewer traditional risks than those with an obstructive coronary artery disease (MI-CAD). MINOCA can be due to either epicardial causes such as rupture or fissuring of unstable nonobstructive atherosclerotic plaque, coronary artery spasm, spontaneous coronary dissection and cardioembolism in-situ or microvascular causes. Besides, also type-2 AMI due to supply-demand mismatch and Takotsubo syndrome must be considered as a possible MINOCA cause. Because of the complex etiology and a limited amount of evidence, there is still some confusion around the management and treatment of these patients. Therefore, the key focus of this condition is to identify the underlying individual mechanisms to achieve patient-specific treatments. Clinical history, electrocardiogram, echocardiography, and coronary angiography represent the first-level diagnostic investigations, but coronary imaging with intravascular ultrasound and optical coherent tomography, coronary physiology testing, and cardiac magnetic resonance imaging offer additional information to understand the underlying cause of MINOCA. Although the prognosis is slightly better compared with MI-CAD patients, MINOCA is not always benign and depends on the etiopathology. This review analyzes all possible pathophysiological mechanisms that could lead to MINOCA and provides the most specific and appropriate therapeutic approach in each scenario.

Perspectives in noninvasive imaging for chronic coronary syndromes.

Both the latest European guidelines on chronic coronary syndromes and the American guidelines on chest pain have underlined the importance of noninvasive imaging to select patients to be referred to invasive angiography. Nevertheless, although coronary stenosis has long been considered the main determinant of inducible ischemia and symptoms, growing evidence has demonstrated the importance of other underlying mechanisms (e.g., vasospasm, microvascular disease, energetic inefficiency). The search for a pathophysiology-driven treatment of these patients has therefore emerged as an important objective of multimodality imaging, integrating "anatomical" and "functional" information. We here provide an up-to-date guide for the choice and the interpretation of the currently available noninvasive anatomical and/or functional tests, focusing on emerging techniques (e.g., coronary flow velocity reserve, stress-cardiac magnetic resonance, hybrid imaging, functional-coronary computed tomography angiography, etc.), which could provide deeper pathophysiological insights to refine diagnostic and therapeutic pathways in the next future.

Clinical outcomes of patients with coronary microvascular dysfunction in absence of obstructive coronary atherosclerosis.

Up to 50% of patients presenting with stable, mainly exercise-induced, chest pain and 10-20% of those admitted to hospital with chest pain suggesting an acute coronary syndrome show normal or near-normal coronary arteries at angiography. Coronary microvascular dysfunction (CMD) is a major cause of symptoms in these patients. However, controversial data exist about their prognosis. In this article, we critically review characteristics and results of the main studies that assessed clinical outcome of patients with angina chest pain and nonobstructive coronary artery disease presenting with either a stable angina pattern or an acute coronary syndrome. Published data indicate that the patients included in most studies are heterogeneous and a major determinant of clinical outcome is the presence of atherosclerotic, albeit not obstructive, coronary artery disease. Long-term prognosis seems instead excellent in patients with totally normal coronary arteries and a syndrome of CMD-related stable angina (microvascular angina). On the other hand, the prognostic impact of CMD in patients presenting with an acute coronary syndrome needs to be better assessed in future studies.

Diagnostic approach for coronary microvascular dysfunction in patients with chest pain and no obstructive coronary artery disease.

A large number of studies has demonstrated that abnormalities of coronary microcirculation may be responsible for both acute and chronic cardiac ischemic syndromes. In clinical practice the microvascular origin of myocardial ischemia and angina is usually considered in patients who are found to have normal or near-normal coronary arteries at angiography. In this article, we review the diagnostic approach to patients with suspected coronary microvascular dysfunction as a cause of ischemic syndromes and also suggest a classification of chronic and acute microvascular coronary ischemic syndrome, including myocardial infarction with normal coronary arteries.

Sex-related differences in ventricular remodeling after myocardial infarction.

The epidemiology, clinical features and outcome of myocardial infarction (MI) display significant differences between men and women. Prominent sex differences have also been suggested in left ventricular (LV) remodeling after MI. Ventricular remodeling refers to a deterioration of LV geometry and function often leading to heart failure (HF) development and an increased risk of adverse cardiovascular events. Women have a lower propensity to the acquisition of a spherical geometry and LV dysfunction. These differences can be attributed at least partially to a lower frequency of transmural infarction and smaller areas of microvascular obstruction in women, as well as to a less prominent activation of neuroendocrine systems and apoptotic, inflammatory and profibrotic pathways in women. Estrogens might play a role in this difference, which could partially persist even after the menopause because of a persisting intramyocardial synthesis of estrogens in women. Conversely, androgens may exert a detrimental influence. Future studies should better clarify sex differences in the predictors, clinical correlates, prognostic impact and disease mechanisms of remodeling, as well as the existence of sex-specific therapeutic targets. This research effort should hopefully allow to optimize the treatment of MI during the acute and post-acute phase, possibly through different therapeutic strategies in men and women, with the goal of reducing the risk of HF development and improving patient outcome.

Pharmacological therapy for the prevention of cardiovascular events in patients with myocardial infarction with non-obstructed coronary arteries (MINOCA): Insights from a multicentre national registry.

AIMS: To assess the effect of pharmacological therapy on long-term prognosis of patients with MINOCA. METHODS AND RESULTS: In this retrospective multicentre cohort study involving 9 Hub Hospitals across Italy we enrolled consecutive patients 18 years and older with diagnosis of MINOCA discharged from 1st March 2012 to 31st March 2018. Data on baseline characteristics and pharmacological therapy at discharge (ACEI/ARB, angiotensin-converting enzyme inhibitors/angiotensin receptor antagonists; ASA, acetylsalicylic acid; beta-blockers; CCB, calcium-channel blockers; DAPT, dual anti-platelet therapy; statins), were collected systematically. The primary endpoint (PE) of the study was a composite of all cause death or acute myocardial infarction or acute coronary syndrome or heart failure leading to hospitalization or stroke. A total of 621 patients were included (mean [SD] age 65.1 [13.9] years; 344 [55.4%] female), of whom 106 (17.1%) experienced PE, including 27 patients (4.3%) who died. Multivariable analysis, after correction for all baseline differences, showed a significant association between pharmacological therapy at discharge and an increased risk of PE for aspirin (HR[95%CI] = 2.47[1.05-5.78], adjusted p = 0.04), whereas beta-blockers were associated with a significant benefit (HR[95%CI] = 0.49 [0.31-0.79], adjusted p = 0.02). CONCLUSION: The use of beta-blockers was significantly associated to a less frequent occurrence of adverse outcomes at long-term follow-up among patients with MINOCA, whereas ASA displayed a potentially harmful impact on prognosis. The findings in the study may be relevant for the design of future studies which should take into account possible heterogeneity among MINOCA patients.

Cardiovascular involvement during COVID-19 and clinical implications in elderly patients. A review.

SARS-CoV-2 betacoronavirus is responsible for the Corona Virus Disease 2019 (COVID-19) which has relevant pathogenic implications for the cardiovascular system. Incidence and severity of COVID-19 are higher in the elderly population (65 years and older). This may be due to higher frequency of comorbidities, but increased frailty and immunosenescence linked with aging may also contribute. Moreover, in elderly individuals, SARS-CoV-2 may adopt different molecular strategies to strongly impact on cardiac aging that culminate in exacerbating a pro-inflammatory state (cytokine storm activation), which, in turn, may lead to pulmonary vascular endothelialitis, microangiopathy, diffuse thrombosis, myocarditis, heart failure, cardiac arrhythmias, and acute coronary syndromes. All these events are particularly relevant in elderly patients, and deserve targeted cardiovascular treatments and specific management of repurposed drugs against COVID-19. We discuss current evidence about the cardiovascular involvement during COVID-19, and elaborate on clinical implications in elderly patients.

Role of endothelial dysfunction in heart failure.

Coronary artery disease is a major underlying etiology for heart failure. The role of coronary microvascular disease, and endothelial dysfunction, in the pathophysiology of heart failure is poorly appreciated. Endothelial dysfunction, induced by oxidative stress, contributes to the development of heart failure. Alterations of endothelial function and nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway are involved in the pathophysiology of heart failure with both reduced and preserved ejection fraction. Indeed, an altered endothelium dependent vasodilatation, causing repeated episodes of ischemia/reperfusion, can induce a chronic stunned myocardium with systolic dysfunction and an increased diastolic stiffness with diastolic dysfunction. Moreover, the altered NO-cGMP pathway directly affects myocardial homeostasis. Endothelial dysfunction is associated with worse prognosis and higher rate of cardiovascular events. Potential therapeutic strategies targeting the NO-cGMP pathway in patients with HF will be discussed in this review article. Although clinical data are still inconclusive, the NO-cGMP pathway represents a promising target for therapy.

Association of diabetes and kidney function according to age and systolic function with the incidence of sudden cardiac death and non-sudden cardiac death in myocardial infarction survivors with heart failure.

AIMS: An implantable cardioverter-defibrillator (ICD) is recommended for reducing the risk of sudden cardiac death (SCD) in myocardial infarction (MI) patients with a left ventricular ejection fraction (LVEF) ≤ 30%, as well as patients with a LVEF ≤ 35% and heart failure symptoms. Diabetes and/or impaired kidney function may confer additional SCD risk. We assessed the association between these two risk factors with SCD and non-SCD among MI survivors taking account of age and LVEF. METHODS AND RESULTS: A total of 17 773 patients from the High-Risk MI Database were evaluated. Overall, diabetes and estimated glomerular filtration rate < 60 mL/min/1.73 m2 , individually and together, conferred a higher risk of SCD [adjusted competing risk: hazard ratio (HR) 1.23, 1.23, and 1.32, respectively; all P < 0.03] and non-SCD (HR 1.34, 1.52, and 2.13, respectively; all P < 0.0001). Annual SCD rates in patients with LVEF > 35% and with diabetes, impaired kidney function, or both (2.0%, 2.5% and 2.7%, respectively) were comparable to rates observed in patients with LVEF 30-35% but no such risk factors (1.7%). However, these patients had also similarly higher non-SCD rates, such that the ratio of SCD to non-SCD was not increased. Importantly, this ratio was mostly dependent on age, with higher overall ratios in youngest subgroups (0.89 in patients < 55 years vs. 0.38 in patients ≥ 75 years), regardless of risk factors. CONCLUSION: Although MI survivors with LVEF > 35% with diabetes, impaired kidney function, or both are at increased risk of SCD, the risk of non-SCD risk is even higher, suggesting an extension of the current indication for an ICD to them is unlikely to be worthwhile. MI survivors with low LVEF and aged < 55 years are likely to have the greatest potential benefit from ICD implantation.

Effects of Sitagliptin on Lipid Profile in Patients With Type 2 Diabetes Mellitus After 7 Years of Therapy.

The aim of this study was to investigate whether the effects of sitagliptin on lipid profile were maintained even after 7 years of treatment. We treated 591 patients who had not been well controlled by current therapy with the addition of sitagliptin 100 mg/d. Data were compared with those of 612 patients treated with sulfonylureas plus metformin, pioglitazone plus metformin, and pioglitazone plus sulfonylureas. We observed that, compared with patients treated with sulfonylureas plus metformin, patients receiving sitagliptin in addition to metformin experienced a greater decrease of total cholesterol and low-density lipoprotein cholesterol (LDL-C) compared with baseline and with sulfonylureas plus metformin. Compared with patients treated with metformin plus pioglitazone, sitagliptin resulted in a greater reduction of total cholesterol and LDL-C relative to baseline and to metformin plus pioglitazone. We also observed a higher increase of high-density lipoprotein cholesterol (HDL-C) after sitagliptin had been added to pioglitazone, both compared with baseline and to the competitor. Compared with patients treated with pioglitazone plus sulfonylureas, the combination of sitagliptin and sulfonylureas was more effective in reducing LDL-C and in increasing HDL-C. High-sensitivity C-reactive protein was decreased by all pharmacological combinations. We can conclude that the addition of sitagliptin led to a better and more durable improvement of lipid profile compared with sulfonylureas or thiazolidinediones.

Predictors of poor clinical outcomes in patients with acute myocardial infarction and non-obstructed coronary arteries (MINOCA).

OBJECTIVE: To assess the characteristics and prognosis of patients with myocardial infarction and non-obstructed coronary arteries (MINOCA). METHODS: MINOCA was defined as acute myocardial infarction (AMI) with angiographic coronary stenosis <50%.Cardiomyopathies and myocarditis were - a priori - excluded from the study. Stenoses <30% were considered normal coronary arteries (NCA); stenoses ≥30% but <50% were considered mild coronary artery disease (MCAD). Patients were subdivided in 3 groups: I) NCA (0 vessels; stenosis <30%); II) 1-2 vessels showing MCAD and III) MCAD in 3 vessels or the left main stem (LMS). RESULTS: From January 2006 to December 2014, 7935 consecutive AMI patients were entered into our institutional database;150 (2%) were diagnosed as having MINOCA. At a median follow-up of 7.1 years the composite end-point (cardiovascular death, AMI or acute coronary syndrome, heart failure, stroke) occurred in 23 patients (17.4%). Survival analysis showed no differences between NCA versus MCAD (p = 0.781). When assessed by distribution of CAD, group III had a lower event-free survival compared to group I and group II, respectively 54 ±â€¯14%, 83 ±â€¯4% and 90 ±â€¯5% (p = 0.001). In a multivariate model, only 3 vessel disease or LMS involvement (HR = 23.5, 95% CI 2.59-173.49, P = 0.001) and high C-reactive protein at hospital admission (HR = 1.47, 95% CI 1.06-2.07, P = 0.005) were significant predictors of the study composite endpoint. CONCLUSIONS: In patients with MINOCA, the presence of NCA or 1-2 vessel MCAD was associated with better long-term clinical outcomes compared with patients with MCAD affecting 3 vessels or the LMS. Increased CRP concentrations on hospital admission were also a marker of worse clinical outcome during follow-up.

Association of beta-blocker treatment with mortality following myocardial infarction in patients with chronic obstructive pulmonary disease and heart failure or left ventricular dysfunction: a propensity matched-cohort analysis from the High-Risk Myocardial Infarction Database Initiative.

AIMS: To determine the influence of baseline beta-blocker use on long-term prognosis of myocardial infarction (MI) survivors complicated with heart failure (HF) or with left ventricular dysfunction and with history of chronic obstructive pulmonary disease (COPD). METHODS AND RESULTS: Among the 28 771 patients from the High-Risk MI Database Initiative we identified 1573 patients with a baseline history of COPD. We evaluated the association between beta-blocker use at baseline (822 with beta-blocker and 751 without) on the rates of all-cause and cardiovascular mortality. On univariable Cox analysis, beta-blocker use was found to be associated with lower rates of both all-cause [hazard ratio (HR) = 0.61, 95% confidence interval (CI) 0.51-0.75, P < 0.0001] and cardiovascular mortality (HR = 0.63, 95% CI 0.51-0.78, P < 0.0001). After extensive adjustment for confounding, including 24 baseline covariates, COPD patients still benefited from beta-blocker usage (HR = 0.73, 95% CI 0.60-0.90, P = 0.002 for all-cause mortality; HR = 0.77, 95% CI 0.61-0.97, P = 0.025 for cardiovascular mortality). Adjusting for propensity scores (PS) constructed from the 24 aforementioned baseline characteristics provided similar results. In a cohort of 561 pairs of patients taking or not taking beta-blocker matched on PS using a 1:1 nearest-neighbour matching method, patients treated with beta-blocker experienced fewer all-cause deaths (HR = 0.71, 95% CI 0.56-0.89, P = 0.003) and cardiovascular deaths (HR = 0.76, 95% CI 0.59-0.97, P = 0.032). CONCLUSIONS: In the specific setting of a well-treated cohort of high-risk MI survivors, beta-blockers were associated with better outcomes in patients with COPD.

Prognostic value of pulmonary congestion assessed by lung ultrasound imaging during heart failure hospitalisation: A two-centre cohort study.

Pulmonary congestion assessed at discharge by lung ultrasonography predicts poor prognosis in heart failure (HF) patients. We investigated the association of B-lines with indices of hemodynamic congestion [BNP, E/e', pulmonary systolic arterial pressure (PAPs)] in HF patients, and their prognostic value overall and according to concomitant atrial fibrillation (AF), reduced (≤40%) ejection fraction (EF), and timing of quantification during hospitalisation for heart failure (HHF). In 110 HHF patients, B-lines were highly discriminative of BNP >400 pg/ml (AUC ≥ 0.80 for all), and moderately discriminative of PAPs >50 mmHg (AUC = 0.68, 0.56 to 0.80); conversely, B-lines poorly discriminated average E/e' ≥ 15, except at discharge. B-line count significantly predicted mid-term recurrent HHF or death (overall and in subgroups), regardless of AF status, EF, and timing of quantification during HHF (all p for interaction >0.10). regardless, B-lines ≥30 at discharge were most predictive of outcome (HR = 7.11, 2.06-24.48; p = 0.002) while B-lines ≥45 early during HHF were most predictive of outcome (HR = 9.20, 1.82-46.61; p = 0.007). Lung ultrasound was able to identify patients with high BNP levels, but not with increased E/e', also showing a prognostic role regardless of AF status, EF or timing of quantification; best B-line cut-off appears to vary according to the timing of quantification during hospitalization.