The term myocardial infarction with non-obstructive coronary arteries (MINOCA), defines a puzzling event occurring in the absence of obstructive coronary artery disease on coronary angiography and ...without an overt potential cause. However, a practical diagnostic work-up is often difficult, due to the heterogeneous etiologies and pathophysiology of MINOCA. This review aims to provide a comprehensive overview focusing on epidemiology, etiopathogenesis, diagnostic tools and therapeutic strategies for subjects with MINOCA, in order to provide a prompt and accurate diagnostic work-up and an adequate therapeutic approach in this subset population.BackgroundThe term myocardial infarction with non-obstructive coronary arteries (MINOCA), defines a puzzling event occurring in the absence of obstructive coronary artery disease on coronary angiography and without an overt potential cause. However, a practical diagnostic work-up is often difficult, due to the heterogeneous etiologies and pathophysiology of MINOCA. This review aims to provide a comprehensive overview focusing on epidemiology, etiopathogenesis, diagnostic tools and therapeutic strategies for subjects with MINOCA, in order to provide a prompt and accurate diagnostic work-up and an adequate therapeutic approach in this subset population.This educational review was carried out by following the standard methods of the Cochrane Collaboration and the PRISMA statement. The terms "MINOCA" OR ("myocardial infarction" AND ("non-obstructive" OR "non-obstructive")) were searched in PubMed and Embase databases (in Title and/or Abstract) from 1st January 2003 until 31st May 2022.MethodsThis educational review was carried out by following the standard methods of the Cochrane Collaboration and the PRISMA statement. The terms "MINOCA" OR ("myocardial infarction" AND ("non-obstructive" OR "non-obstructive")) were searched in PubMed and Embase databases (in Title and/or Abstract) from 1st January 2003 until 31st May 2022.Etiologic findings, clinical presentation and the degree of hemodynamic impairment play a pivotal role in defining the patient's natural history and prognostic outcome, and may significantly impact on the decision-making strategies and therapeutic approaches.ResultsEtiologic findings, clinical presentation and the degree of hemodynamic impairment play a pivotal role in defining the patient's natural history and prognostic outcome, and may significantly impact on the decision-making strategies and therapeutic approaches.Despite further advances in diagnostic and therapeutic strategies, MINOCA remains a challenging conundrum in clinical practice. Clinicians should be aware of the different potential etiologies and pathogenic mechanisms of MINOCA, in order to carry out a comprehensive diagnostic work-up and implement a tailored therapeutic approach.ConclusionsDespite further advances in diagnostic and therapeutic strategies, MINOCA remains a challenging conundrum in clinical practice. Clinicians should be aware of the different potential etiologies and pathogenic mechanisms of MINOCA, in order to carry out a comprehensive diagnostic work-up and implement a tailored therapeutic approach.
(1) Introduction. Although pulmonary arterial hypertension (PAH) usually affects young people with a low cardiovascular risk profile, progressive epidemiologic changes have been providing a codified ...phenotype of elderly subjects with PAH and increased risk predictors for left heart disease. We therefore conducted a systematic review to describe the current knowledge and characteristics of elderly individuals with PAH and further insights concerning their prognostic outcomes and therapeutic response. (2) Methods. A search was conducted in PubMed, Embase, and Cochrane Library for publications evaluating the epidemiology, diagnostic work-up, and treatment of PAH in elderly subjects. (3) Among the 74 publications initially retrieved, 16 full-text articles were selected for the present systematic review. Compared to their younger counterparts, elderly individuals with PAH showed greater clinical deterioration, reduced exercise capacity, and worse prognostic outcomes, as well as less response to PAH-targeted therapy and higher rates of PAH drug discontinuation. (4) Conclusions. Demographic changes over time contributed to define a peculiar PAH phenotype in elderly patients, with an increased burden of cardiovascular comorbidities and distinctive features compared to young patients. Further investigations are needed in order to better clarify the nosologic criteria, and management in this subset population.
Peri-procedural myocardial injury (PPMI) is a common complication after transcatheter valve replacement (TAVR), often remaining clinically silent. The role of valve type on PPMI and the association ...between PPMI and mortality are still unclear. We sought to evaluate predictors and outcome of PPMI after TAVR, and the impact of self-expandable valve (SEV) vs. balloon-expandable valve (BEV) deployment on PPMI. Consecutive patients who underwent successful TAVR in a single-center from January 2014 to December 2019 were included. PPMI was defined according to a modified Valve Academic Research Consortium (VARC)-2 definition as a post-procedure elevation of troponin (with a peak value ≥ 15-times the upper-reference limit) < 72 h after TAVR. We included 596 patients, of whom 258 (43.3%) were men. Mean age was 83.4 ± 5.5 years. We deployed 368 (61.7%) BEV and 228 (38.3%) SEV. PPMI was observed in 471 (79.0%) patients. At multivariable analysis, SEV (OR 2.70, 95% CI 1.64–4.55,
p
< 0.001), creatinine clearance (OR 0.98, 95% CI 0.97–1.00,
p
= 0.011), and baseline ejection fraction (OR 1.05, 95% CI 1.02–1.07,
p
< 0.001) were independent predictors of PPMI; these findings were also confirmed using a propensity-weighted analysis. Thirty-day and 1-year all-cause mortality rates were 2.5% and 8.1%, respectively. No associations between PPMI and 30-day (
p
= 0.488) or 1-year (
p
= 0.139) all-cause mortality were found. Independent predictors of 30-day mortality were increasing EUROSCORE II (HR 1.16 per score point, 95% CI 1.08–1.19,
p
< 0.001) and life-threatening/major bleeding complications (HR 5.87, 95% CI 1.28–26.58,
p
= 0.019), whereas EUROSCORE II (HR 1.08, 95% CI 1.04–1.13,
p
= 0.031) and acute kidney injury (HR 2.59, 95% CI 1.20–5.35,
p
= 0.020) were related to 1-year mortality. PPMI is frequent after TAVR, but it does not affect 30-day or 1-year all-cause mortality. SEV implantation is associated with an increased frequency of PPMI.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Doxorubicin (DOX)-based chemotherapy for Hodgkin lymphoma (HL) yields excellent disease-free survival, but poses a substantial risk of subsequent left ventricular (LV) dysfunction and heart failure, ...typically with delayed onset. At the cellular level, this cardiotoxicity includes deranged cardiac glucose metabolism.
By reviewing the hospital records from January 2008 through December 2016, we selected HL patients meeting the following criteria: ≥ 18 year-old; first-line DOX-containing chemotherapy; no diabetes and apparent cardiovascular disease; 18-fluoro-deoxyglucose positron emission tomography (
FDG-PET) scans before treatment (PET
), after 2 cycles (PET
) and at the end of treatment (PET
); at least one echocardiography ≥ 6 months after chemotherapy completion (ECHO
). We then evaluated the changes in LV
FDG standardized uptake values (SUV) during the course of DOX therapy, and the relationship between LV-SUV and LV ejection fraction (LVEF), as calculated from the LV diameters in the echocardiography reports with the Teicholz formula.
Forty-three patients (35 ± 13 year-old, 58% males) were included in the study, with 26 (60%) also having a baseline echocardiography available (ECHO
). LV-SUV gradually increased from PET
(log-transformed mean 0.20 ± 0.27) to PET
(0.27 ± 0.35) to PET
(0.30 ± 0.41; P for trend < 0.001). ECHO
was performed 22 ± 17 months after DOX chemotherapy. Mean LVEF was normal (68.8 ± 10.3%) and only three subjects (7%) faced a drop below the upper normal limit of 53%. However, when patients were categorized by median LV-SUV, LVEF at ECHO
resulted significantly lower in those with LV-SUV above than below the median value at both PET
(65.5 ± 11.8% vs. 71.9 ± 7.8%, P = 0.04) and PET
(65.6 ± 12.2% vs. 72.2 ± 7.0%, P = 0.04). This was also the case when only patients with ECHO
and ECHO
were considered (LVEF at ECHO
64.7 ± 8.9% vs. 73.4 ± 7.6%, P = 0.01 and 64.6 ± 9.3% vs. 73.5 ± 7.0%, P = 0.01 for those with LV-SUV above vs. below the median at PET
and PET
, respectively). Furthermore, the difference between LVEF at ECHO
and ECHO
was inversely correlated with LV-SUV at PET
(P < 0.01, R
= - 0.30).
DOX-containing chemotherapy causes an increase in cardiac
FDG uptake, which is associated with a decline in LVEF. Future studies are warranted to understand the molecular basis and the potential clinical implications of this observation.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The past two decades have witnessed rapid and remarkable technical improvement of multidetector computed tomography (CT) in both image quality and diagnostic accuracy. These improvements include ...higher temporal resolution, high-definition and wider detectors, the introduction of dual-source and dual-energy scanners, and advanced postprocessing. Current new generation multidetector row (≥64 slices) CT systems allow an accurate and reliable assessment of both coronary epicardial stenosis and myocardial CT perfusion (CTP) imaging at rest and during pharmacologic stress in the same examination. This novel application makes CT the unique noninvasive “one-stop-shop” method for a comprehensive assessment of both anatomical coronary atherosclerosis and its physiological consequences. Myocardial CTP imaging can be performed with different approaches such as static arterial first-pass imaging, and dynamic CTP imaging, with their own advantages and disadvantages. Static CTP can be performed using single-energy or dual-energy CT, employing qualitative or semiquantitative analysis. In addition, dynamic CTP can obtain quantitative data of myocardial blood flow and coronary flow reserve. The purpose of this review was to summarize all available evidence about the emerging role of myocardial CTP to identify ischemia-associated lesions, focusing on technical considerations, clinical applications, strengths, limitations, and the more promising future fields of interest in the broad spectra of ischemic heart disease.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
We report a case of simultaneous transcatheter aortic valve replacement and endovascular aneurysm repair. Our aim was to advocate the role of local and regional anesthesia as a key contributor in ...maintaining hemodynamic stability and avoiding abrupt blood pressure change. Endovascular combined procedures are gaining popularity for their numerous advantages. Nevertheless, they carry significant risks for their hemodynamic implications. It is imperative to acknowledge the modifications occurring after each correction and act accordingly. Different anesthesia approaches can dramatically influence hemodynamics; among all, we found local and regional anesthesia would better serve this objective.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Acute kidney injury (AKI) may complicate transcatheter aortic valve replacement (TAVR) leading to higher mortality. The relationship between AKI, obesity, and mortality, however, is controversial. We ...sought to investigate the impact of body habitus on the prognostic value of AKI in TAVR.
Among the 645 patients who underwent successful TAVR in a single high-volume centre, we retrospectively evaluated the association between AKI-TAVR and 30-day, 6-month, and 1-year mortality, and whether this relationship was affected by BMI. AKI was defined according to the Valve Academic Research Consortium-2 criteria. Patients were categorized into three groups by BMI: low-to-normal weight (<25 kg/m2), overweight (25-30 kg/m2), obese (>30.0 kg/m2).
Three-hundred and twenty-four (50.2%) patients were low-to-normal weight, 223 (34.6%) overweight, and 98 (15.2%) obese. AKI occurred in 141 (21.9%), similarly across BMI groups. Thirty-day, 6-month, and 1-year mortality rates were 2.2, 3.7, and 7.9%, without differences across BMI groups. Among patients who developed AKI-TAVR, 30-day (8.7 vs. 2.0 vs. 0.0%), 6-month (13.0 vs. 6.1 vs. 4.3%), and 1-year (20.3 vs. 12.2 vs. 4.3%) mortality showed a decreasing trend across increasing BMI categories (all P < 0.05); the same trend was not observed for patients without AKI-TAVR. In multivariate models, AKI was associated with 30-day odds ratio (OR): 2.46, 95% confidence interval (CI): 1.70-8.67, 6-month (OR: 2.75, 95% CI: 1.32-7.59), and 1-year mortality (OR: 1.84, 95% CI: 1.22-3.71, all P < 0.05). The interaction between AKI and BMI, when added to the models, was consistently significant (all P < 0.05).
Higher BMI is associated with better survival in TAVR patients who develop AKI.
Local accumulation of Advanced Oxidation Protein Products (AOPP) induces pro-inflammatory and pro-fibrotic processes in kidneys and is an independent predictor of renal fibrosis and of rapid decline ...of eGFR in patients with chronic kidney disease (CKD). In addition to kidney damage, circulating AOPP may be regarded as mediators of systemic oxidative stress and, in this capacity, they might play a role in the progression of atherosclerotic damage of arterial walls. Atherosclerosis is a chronic inflammatory disease that involves activation of innate and adaptive immunity. Dendritic cells (DCs) are key cells in this process, due to their role in antigen presentation, inflammation resolution and T cell activation. AOPP consist in oxidative modifications of proteins (such as albumin and fibrinogen) that mainly occur through myeloperoxidase (MPO)-derived hypochlorite (HOCl). HOCl modified proteins have been found in atherosclerotic lesions. The oxidizing environment and the shifts in cellular redox equilibrium trigger inflammation, activate immune cells and induce immune responses. Thus, surface thiol groups contribute to the regulation of immune functions. The aims of this work are: (1) to evaluate whether AOPP-proteins induce activation and differentiation of mature macrophages into dendritic cells in vitro; and (2) to define the role of cell surface thiol groups and of free radicals in this process. AOPP-proteins were prepared by in vitro incubation of human serum albumin (HSA) with HOCl. Mouse macrophage-like RAW264.7 were treated with various concentrations of AOPP-HSA with or without the antioxidant
-acetyl cysteine (NAC). Following 48 h of HSA-AOPP treatment, RAW264.7 morphological changes were evaluated by microscopic observation, while markers of dendritic lineage and activation (CD40, CD86, and MHC class II) and allogeneic T cell proliferation were evaluated by flow cytometry. Cell surface thiols were measured by AlexaFluor-maleimide binding, and ROS production was assessed as DCF fluorescence by flow cytometry. HSA-AOPP induced the differentiation of RAW264.7 cells into a dendritic-like phenotype, as shown by morphological changes, by increased CD40, CD86 and MHC class II surface expression and by induction of T cell proliferation. The cell surface thiols dose dependently decreased following HSA-AOPP treatment, while ROS production increased. NAC pre-treatment enhanced the amount of cell surface thiols and prevented their reduction due to treatment with AOPP. Both ROS production and RAW264.7 differentiation into DC-like cells induced by HSA-AOPP were reduced by NAC. Our results highlight that oxidized plasma proteins modulate specific immune responses of macrophages through a process involving changes in the thiol redox equilibrium. We suggest that this mechanism may play a role in determining the rapid progression of the atherosclerotic process observed in CKD patients.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background Acute kidney injury (AKI) after transcatheter aortic valve replacement (TAVR) is associated with increased mortality. However, it is controversial whether AKI affects prognosis per se, ...being linked to baseline chronic kidney disease (CKD) and bleeding complications. The aim of this study was to disentangle, applying mediation analysis, the association between AKI and clinical outcome, considering CKD and bleedings. Methods and Results Consecutive patients undergoing TAVR were prospectively enrolled at 5 high‐volume centers in Italy. AKI was defined according to Valve Academic Research Consortium‐3 consensus, whereas bleeding with Bleeding Academic Research Consortium. Primary outcome was all‐cause mortality after 1‐year follow‐up. Among 2621 patients undergoing TAVR, AKI occurrence was associated with 1‐year mortality. This association of AKI with the primary end points remained significant after adjusting for baseline risk estimators, either Society of Thoracic Surgeons score (hazard ratio HR, 2.78 95% CI, 1.95–3.80, P <0.001) or EuroSCORE‐II (HR, 1.85 95% CI, 1.35–2.56, P <0.001). Both AKI and CKD significantly and independently affected primary outcome (HR, 3.06 95% CI, 2.01–4.64, P <0.001 and HR, 1.82 95% CI 1.27–2.65, P <0.01, respectively). The estimated proportion of the total effect of CKD mediated via AKI was, on average, 15%, 95% CI, 4%–29%, P <0.001. The significant effect of Bleeding Academic Research Consortium 2–5 bleedings on the primary outcome was not mediated by AKI. Conclusions AKI occurs in 1 out of 6 patients and significantly mediates one fifth of the effect of baseline CKD on all‐cause mortality after TAVR. Our analysis supports a systematic effort to prevent AKI during TAVR, which may potentially translate into improved patients' 1‐year survival.
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