The coronary microcirculation plays a key role in modulating blood supply to the myocardium. Several factors like myocardial oxygen demands, endothelial and neurogenic conditions determine its function. Although there is available evidence supporting microvascular dysfunction as an important cause of myocardial ischaemia, with both prognostic and symptomatic implications, its diagnosis and management in clinical practice is still relegated to a second plane. Both diagnostic and therapeutic approaches are hampered by the broadness of the concept of microvascular dysfunction, which fails addressing the plurality of mechanisms leading to dysfunction. Normal microcirculatory function requires both structural integrity of the microcirculatory vascular network and preserved signalling pathways ensuring adequate and brisk arteriolar resistance shifts in response to myocardial oxygen demands. Pathological mechanisms affecting these requirements include structural remodelling of microvessels, intraluminal plugging, extravascular compression or vasomotor dysregulation. Importantly, not every diagnostic technique provides evidence on which of these pathophysiological mechanisms is present or predominates in the microcirculation. In this paper we discuss the mechanisms of coronary microvascular dysfunction and the intracoronary tools currently available to detect it, as well as the potential role of each one to unmask the main underlying mechanism.

ImportanceAnthracyclines treat a broad range of cancers. Basic and retrospective clinical data have suggested that use of atorvastatin may be associated with a reduction in cardiac dysfunction due to anthracycline use.ObjectiveTo test whether atorvastatin is associated with a reduction in the proportion of patients with lymphoma receiving anthracyclines who develop cardiac dysfunction.Design, Setting, and ParticipantsDouble-blind randomized clinical trial conducted at 9 academic medical centers in the US and Canada among 300 patients with lymphoma who were scheduled to receive anthracycline-based chemotherapy. Enrollment occurred between January 25, 2017, and September 10, 2021, with final follow-up on October 10, 2022.InterventionsParticipants were randomized to receive atorvastatin, 40 mg/d (n = 150), or placebo (n = 150) for 12 months.Main Outcomes and MeasuresThe primary outcome was the proportion of participants with an absolute decline in left ventricular ejection fraction (LVEF) of ≥10% from prior to chemotherapy to a final value of <55% over 12 months. A secondary outcome was the proportion of participants with an absolute decline in LVEF of ≥5% from prior to chemotherapy to a final value of <55% over 12 months.ResultsOf the 300 participants randomized (mean age, 50 [SD, 17] years; 142 women [47%]), 286 (95%) completed the trial. Among the entire cohort, the baseline mean LVEF was 63% (SD, 4.6%) and the follow-up LVEF was 58% (SD, 5.7%). Study drug adherence was noted in 91% of participants. At 12-month follow-up, 46 (15%) had a decline in LVEF of 10% or greater from prior to chemotherapy to a final value of less than 55%. The incidence of the primary end point was 9% (13/150) in the atorvastatin group and 22% (33/150) in the placebo group (P = .002). The odds of a 10% or greater decline in LVEF to a final value of less than 55% after anthracycline treatment was almost 3 times greater for participants randomized to placebo compared with those randomized to atorvastatin (odds ratio, 2.9; 95% CI, 1.4-6.4). Compared with placebo, atorvastatin also reduced the incidence of the secondary end point (13% vs 29%; P = .001). There were 13 adjudicated heart failure events (4%) over 24 months of follow-up. There was no difference in the rates of incident heart failure between study groups (3% with atorvastatin, 6% with placebo; P = .26). The number of serious related adverse events was low and similar between groups.Conclusions and RelevanceAmong patients with lymphoma treated with anthracycline-based chemotherapy, atorvastatin reduced the incidence of cardiac dysfunction. This finding may support the use of atorvastatin in patients with lymphoma at high risk of cardiac dysfunction due to anthracycline use.Trial RegistrationClinicalTrials.gov Identifier: NCT02943590

BackgroundContrast-induced encephalopathy (CIE) is a rare complication of coronary angiography (CAG) caused by a direct neurotoxic reaction to iodinated contrast medium. Contrast-induced encephalopathy can result in a variety of neurological symptoms following within minutes to hours after contrast injection. It manifests most frequently as transient cortical blindness, headache, or confusion. In the majority of known cases, symptoms completely resolve solely with supportive care. We present a case where CIE takes a more dramatic course.Case summaryA 67-year-old woman was scheduled for elective CAG, due to progressive typical chest pain. Within minutes after injection of iso-osmolar iodinated contrast medium, the patient showed a sudden decline in consciousness while all other vital functions remained normal. Shortly, after the patient was admitted to the intensive care unit due to acute-onset coma and respiratory insufficiency. A computed tomography scan of the brain showed bilateral cerebral oedema, which in combination with the development of symptoms after contrast injection led to the diagnosis of CIE. Remarkable decrease of cerebral oedema was observed 1 day later and slowly clinical recovery ensued. After 23 days, the patient was discharged from the cardiology ward. Follow-up at the outpatient clinic showed no lasting neurological deficits.Discussion While most symptoms of CIE are relatively mild and transient in nature, we describe a more devastating course that occurred with the use of only a low quantity of iso-osmolar contrast medium. We emphasize that even the more severe manifestations of CIE can develop at any dosage, and with all types of iodinated contrast medium.

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Background Thoracic irradiation is one of the cornerstones of Hodgkin lymphoma (HL) treatment, which contributes to high rates of long-term survivorship, but begets a life-long increased risk of heart disease including heart failure. At the cardio-oncology (CO) clinic, persistent sinus tachycardia or elevated resting heart rate (RHR) is frequently observed in these patients. The aim of this study was to evaluate the relation between RHR and left ventricular (LV) dysfunction. Methods In 75 HL survivors visiting our CO-clinic echocardiographic evaluation of LV systolic and diastolic function including global longitudinal strain (GLS) was performed to assess subclinical LV dysfunction. Results Median age of HL diagnosis was 24 [25th-75th percentile: [19] , [29] ] years with a 17 [12] , [25] year interval to CO-clinic visit and 31 patients (41%) were male. Average RHR was 78 ± 14 bpm and 40% of patients (N = 30) had an elevated RHR defined as ≥ 80 bpm. While there was no difference in LV ejection fraction (55.6 ± 4.3 vs . 54.8 ± 6.6; p = 0.543), patients with elevated RHR had abnormal GLS (-15.9% vs . −18.3%, p = 0.045) and higher prevalence of diastolic dysfunction (73.3% vs . 46.7%; p = 0.022). GLS, E/e’ ratio and presence of diastolic dysfunction were independently associated with RHR when correcting for age, sex and mantle field irradiation. A significant improvement was observed of the RHR-association model with solely extracardiac confounders when LV-function parameters were added to the model (F-statistic = 6.36, p = 0.003). Conclusions This study indicates RHR as a possible marker for subclinical LV-dysfunction in HL survivors.

Immune checkpoint inhibitors (ICIs) are a form immunotherapy where the negative regulators of host immunity are targeted, thereby leveraging the own immune system. ICIs have significantly improved cancer survival in several advanced malignancies and there are currently over 90 different cancer indications for ICIs. The majority of patients develop immune-related adverse events (irAEs) during ICI therapy. Most are mild but a small subset of patients will develop severe and potentially fatal irAEs. A serious cardiovascular complication of ICI therapy is myocarditis. While the incidence of myocarditis is low, mortality rates of up to 50% have been reported. The mainstay of ICI associated myocarditis treatment is high-dose corticosteroids. Unfortunately, half of patients with myocarditis do not show clinical improvement after corticosteroid treatment. Also, high doses of corticosteroids may adversely impact cancer outcomes. There is an evidence gap in the optimal second-line treatment strategy. Currently, there is a paradigm shift in second-line treatment taking place from empirical corticosteroid-only strategies to either intensified initial immunosuppression where corticosteroids are combined with another immunosuppressant or targeted therapies directed at the pathophysiology of ICI myocarditis. However, the available evidence to support these novel strategies is limited to observational studies and case reports. The aim of this review is to summarize the literature, guidelines, and future directions on the pharmacological treatment of ICI myocarditis.

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Background/Purpose. We aimed to investigate the influence of the sampling site on the variability of ACT measurement. Activated clotting time (ACT) has been used for decades in cardiac surgery and interventional cardiology to assess unfractionated heparin activity. However, standardized protocols for the use of ACT measurement in the catheterization laboratory are lacking. Methods/Materials. After elective cardiac catheterization, ACT measurements were collected in simultaneously obtained blood samples from three different sample sites: the arterial catheter, arterial sheath, and peripheral intravenous line. Measurements were performed using the i-Stat® device (Abbott, Princeton, NJ, USA). The study was conducted with approval of the local medical ethical committee. Results. In 100 patients (mean age 67.1, 65% male), no significant differences were observed in ACT values obtained from the guiding catheter and arterial sheath (mean difference (MD) −18.3 s; standard deviation (SD) 96 s; P = 0.067 ). Contrarily, ACT values obtained from the intravenous line were significantly lower as compared to values obtained from the guiding catheter (MD 25.7 s; SD 75.5; P = 0.003 ) and arterial sheath (MD 39 s; SD 102.8; P < 0.001 ). Furthermore, ACT measurements from the arterial sheath showed a statistically significant proportional bias when compared to the other sampling sites (sheath vs. catheter, r = 0.761, P = 0.001 ; sheath vs. IVL, r = 1.013, P < 0.001 ). Conclusions. The present study shows statistical significance and possibly clinically relevant variations between ACT measurements from different sample sites. Bias in ACT measurements may be minimized by using uniform protocols for ACT measurement during cardiac catheterization.