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Cardiac sarcoidosis (CS) results from epithelioid cell granulomas infiltrating the myocardium and predisposing to conduction disturbances, ventricular tachyarrhythmias, and heart failure. Manifest CS, however, constitutes only the top of an iceberg as advanced imaging uncovers cardiac involvement 4 to 5 times more commonly than what is clinically detectable. Definite diagnosis of CS requires myocardial biopsy and histopathology, but a sufficient diagnostic likelihood can be achieved by combining extracardiac histology of sarcoidosis with clinical manifestations and findings on cardiac imaging. CS can appear as the first or only organ manifestation of sarcoidosis or on top of pre-existing extracardiac disease. Due to the lack of controlled trials, the care of CS is based on observational evidence of low quality. Currently, the treatment involves corticosteroid-based, tiered immunosuppression to control myocardial inflammation with medical and device-based therapy for symptomatic atrioventricular block, ventricular tachyarrhythmias, and heart failure. Recent outcome data indicate 90% to 96% 5-year survival in manifest CS with the 10-year figures ranging from 80% to 90%. Major progress in the care of CS awaits the key to its molecular–genetic pathogenesis and large-scale controlled clinical trials.

Background: Cardiac sarcoidosis (CS) predisposes to sudden cardiac death (SCD). Guidelines for implantable cardioverter defibrillators (ICDs) in CS have been issued by the Heart Rhythm Society in 2014 and the American College of Cardiology/American Heart Association/Heart Rhythm Society consortium in 2017. How well they discriminate high from low risk remains unknown. Methods: We analyzed the data of 398 patients with CS detected in Finland from 1988 through 2017. All had clinical cardiac manifestations. Histological diagnosis was myocardial in 193 patients (definite CS) and extracardiac in 205 (probable CS). Patients with and without Class I or IIa ICD indications at presentation were identified, and subsequent occurrences of SCD (fatal or aborted) and sustained ventricular tachycardia were recorded, as were ICD indications emerging first on follow-up. Results: Over a median of 4.8 years, 41 patients (10.3%) had fatal (n=8) or aborted (n=33) SCD, and 98 (24.6%) experienced SCD or sustained ventricular tachycardia as the first event. By the Heart Rhythm Society guideline, Class I or IIa ICD indications were present in 339 patients (85%) and absent in 59 (15%), of whom 264 (78%) and 30 (51%), respectively, received an ICD. Cumulative 5-year incidence of SCD was 10.7% (95% CI, 7.4%–15.4%) in patients with ICD indications versus 4.8% (95% CI, 1.2%–19.1%) in those without (χ 2 =1.834, P =0.176). The corresponding rates of SCD were 13.8% (95% CI, 9.1%–21.0%) versus 6.3% (95% CI, 0.7%–54.0%; χ 2 =0.814, P =0.367) in definite CS and 7.6% (95% CI, 3.8%–15.1%) versus 3.3% (95% CI, 0.5%–22.9%; χ 2 =0.680, P =0.410) in probable CS. In multivariable regression analysis, SCD was predicted by definite histological diagnosis ( P =0.033) but not by Class I or IIa ICD indications ( P =0.210). In patients without ICD indications at presentation, 5-year incidence of SCD, sustained ventricular tachycardia, and emerging Class I or IIa indications was 53% (95% CI, 40%–71%). By the American College of Cardiology/American Heart Association/Heart Rhythm Society guideline, all patients with complete data (n=245) had Class I or IIa indications for ICD implantation. Conclusions: Current ICD guidelines fail to distinguish a truly low-risk group of patients with clinically manifest CS, the 5-year risk of SCD approaching 5% despite absent ICD indications. Further research is needed on prognostic factors, including the role of diagnostic histology. Meanwhile, all patients with CS presenting with clinical cardiac manifestations should be considered for an ICD implantation.

Patients infected with SARS-CoV-2 have varying manifestations of cardiac involvement. We report four patients presenting with symptomatic cardiac sarcoidosis (CS) or giant cell myocarditis (GCM) 1-8 months after mild COVID-19. All patients received immunosuppressive therapy and improved gradually within the following months. The possible temporal association between the CS/GCM and COVID-19 infection might suggest that COVID-19 could be a trigger for granulomatous myocarditis.

Aims Giant cell myocarditis (GCM) is an inflammatory cardiomyopathy akin to cardiac sarcoidosis (CS). We decided to study the findings of GCM on cardiac magnetic resonance (CMR) imaging and to compare GCM with CS. Methods and results CMR studies of 18 GCM patients were analyzed and compared with 18 CS controls matched for age, sex, left ventricular (LV) ejection fraction and presenting cardiac manifestations. The analysts were blinded to clinical data. On admission, the duration of symptoms (median) was 0.2 months in GCM vs. 2.4 months in CS (P = 0.002), cardiac troponin T was elevated (>50 ng/L) in 16/17 patients with GCM and in 2/16 with CS (P < 0.001), their respective median plasma B-type natriuretic propeptides measuring 4488 ng/L and 1223 ng/L (P = 0.011). On CMR imaging, LV diastolic volume was smaller in GCM (177 ± 32 mL vs. 211 ± 58 mL, P = 0.014) without other volumetric or wall thickness measurements differing between the groups. Every GCM patient had multifocal late gadolinium enhancement (LGE) in a distribution indistinguishable from CS both longitudinally, circumferentially, and radially across the LV segments. LGE mass averaged 17.4 ± 6.3% of LV mass in GCM vs 25.0 ± 13.4% in CS (P = 0.037). Involvement of insertion points extending across the septum into the right ventricular wall, the “hook sign” of CS, was present in 53% of GCM and 50% of CS. Conclusion In GCM, CMR findings are qualitatively indistinguishable from CS despite myocardial inflammation being clinically more acute and injurious. When matched for LV dysfunction and presenting features, LV size and LGE mass are smaller in GCM.

Background Acute myocarditis (AM) is thought to be a rare cardiovascular complication of COVID-19, although minimal data are available beyond case reports. We aim to report the prevalence, baseline characteristics, in-hospital management, and outcomes for patients with COVID-19–associated AM on the basis of a retrospective cohort from 23 hospitals in the United States and Europe. Methods A total of 112 patients with suspected AM from 56963 hospitalized patients with COVID-19 were evaluated between February 1, 2020, and April 30, 2021. Inclusion criteria were hospitalization for COVID-19 and a diagnosis of AM on the basis of endomyocardial biopsy or increased troponin level plus typical signs of AM on cardiac magnetic resonance imaging. We identified 97 patients with possible AM, and among them, 54 patients with definite/probable AM supported by endomyocardial biopsy in 17 (31.5%) patients or magnetic resonance imaging in 50 (92.6%). We analyzed patient characteristics, treatments, and outcomes among all COVID-19–associated AM. Results AM prevalence among hospitalized patients with COVID-19 was 2.4 per 1000 hospitalizations considering definite/probable and 4.1 per 1000 considering also possible AM. The median age of definite/probable cases was 38 years, and 38.9% were female. On admission, chest pain and dyspnea were the most frequent symptoms (55.5% and 53.7%, respectively). Thirty-one cases (57.4%) occurred in the absence of COVID-19–associated pneumonia. Twenty- one (38.9%) had a fulminant presentation requiring inotropic support or temporary mechanical circulatory support. The composite of in-hospital mortality or temporary mechanical circulatory support occurred in 20.4%. At 120 days, estimated mortality was 6.6%, 15.1% in patients with associated pneumonia versus 0% in patients without pneumonia (P=0.044). During hospitalization, left ventricular ejection fraction, assessed by echocardiography, improved from a median of 40% on admission to 55% at discharge (n=47; P Conclusions AM occurrence is estimated between 2.4 and 4.1 out of 1000 patients hospitalized for COVID-19. The majority of AM occurs in the absence of pneumonia and is often complicated by hemodynamic instability. AM is a rare complication in patients hospitalized for COVID-19, with an outcome that differs on the basis of the presence of concomitant pneumonia.

Aims Cardiac sarcoidosis (CS) and giant cell myocarditis (GCM) are inflammatory cardiomyopathies sharing histopathological and clinical features. Their differentiation is difficult and susceptible of confusion and apparent mistakes. The possibility that they represent different phenotypes of a single disease has been debated. Methods and results We made a retrospective audit of 73 cases of GCM diagnosed in Finland since the late 1980s. All available histological material was reanalyzed as were other examinations pertinent to the distinction between GCM and CS. Finding granulomas in or outside the heart was considered diagnostic of CS and exclusive of GCM. Altogether 45 of the 73 cases of GCM (62%) were reclassified as CS. In all except one case, this was based on finding sarcoid granulomas that either had been originally missed (n = 29) or misinterpreted (n = 11) or were found in additional posttransplant myocardial specimens (n = 3) or samples of extracardiac tissue (n = 1) accrued over the disease course. Supporting the reclassification, patients relocated to the CS group had less heart failure at presentation (prevalence 20% vs. 46%, P = 0.017) and better 1 year transplant-free survival (82% vs. 45%, P = 0.011) than patients considered to represent true GCM. Conclusions Recognizing granulomas in or outside the heart remains a challenge for the pathologist. Given that CS and GCM are considered distinct diseases and granulomas exclusive of GCM, many cases of GCM, if thoroughly scrutinized, may need reclassification as CS. However, whether CS and GCM are truly different entities or parts of a one-disease continuum has not yet been conclusively settled.

Background Some myocardial diseases, such as cardiac sarcoidosis, predispose to complete atrioventricular block. The European Society of Cardiology Guidelines on cardiac pacing in 2021 recommend myocardial disease screening in patients with conduction disorder requiring pacemaker with multimodality imaging, including cardiac magnetic resonance (CMR) imaging. The ability of CMR imaging to detect myocardial disease in patients with a temporary pacing wire is not well documented. Methods and Results Our myocardial disease screening protocol is based on using an active fixation pacing lead connected to a reusable extracorporeal pacing generator (temporary permanent pacemaker) as a bridge to a permanent pacemaker. From 2011 to 2019, we identified 17 patients from our CMR database who underwent CMR imaging with a temporary permanent pacemaker for atrioventricular block. We analyzed their clinical presentations, CMR data, and pacemaker therapy. All CMRs were performed without adverse events. Pacing leads induced minor artifacts to the septal myocardial segments. The extent of late gadolinium enhancement in CMR imaging was used to screen patients for the presence of myocardial disease. Patients with evidence of late gadolinium enhancement underwent endomyocardial biopsy. If considered clinically indicated, also 18‐F‐fluorodeoxyglucose positron emission tomography and extracardiac tissue biopsy were performed if sarcoidosis was suspected. Eventually, 8 of 17 patients (47.1%) were diagnosed with histologically confirmed granulomatous inflammatory cardiac disease. Importantly, only 1 had a previously diagnosed extracardiac sarcoidosis at the time of presentation with high‐degree atrioventricular block. Conclusions CMR imaging with temporary permanent pacemaker protocol is an effective and safe early screening tool for myocardial disease in patients presenting with atrioventricular block requiring immediate, continuous pacing for bradycardia.

Background: Acute myocarditis (AM) is thought to be a rare cardiovascular complication of COVID-19, although minimal data are available beyond case reports. We aim to report the prevalence, baseline characteristics, in-hospital management, and outcomes for patients with COVID-19–associated AM on the basis of a retrospective cohort from 23 hospitals in the United States and Europe. Methods: A total of 112 patients with suspected AM from 56 963 hospitalized patients with COVID-19 were evaluated between February 1, 2020, and April 30, 2021. Inclusion criteria were hospitalization for COVID-19 and a diagnosis of AM on the basis of endomyocardial biopsy or increased troponin level plus typical signs of AM on cardiac magnetic resonance imaging. We identified 97 patients with possible AM, and among them, 54 patients with definite/probable AM supported by endomyocardial biopsy in 17 (31.5%) patients or magnetic resonance imaging in 50 (92.6%). We analyzed patient characteristics, treatments, and outcomes among all COVID-19–associated AM. Results: AM prevalence among hospitalized patients with COVID-19 was 2.4 per 1000 hospitalizations considering definite/probable and 4.1 per 1000 considering also possible AM. The median age of definite/probable cases was 38 years, and 38.9% were female. On admission, chest pain and dyspnea were the most frequent symptoms (55.5% and 53.7%, respectively). Thirty-one cases (57.4%) occurred in the absence of COVID-19–associated pneumonia. Twenty-one (38.9%) had a fulminant presentation requiring inotropic support or temporary mechanical circulatory support. The composite of in-hospital mortality or temporary mechanical circulatory support occurred in 20.4%. At 120 days, estimated mortality was 6.6%, 15.1% in patients with associated pneumonia versus 0% in patients without pneumonia ( P =0.044). During hospitalization, left ventricular ejection fraction, assessed by echocardiography, improved from a median of 40% on admission to 55% at discharge (n=47; P Conclusions: AM occurrence is estimated between 2.4 and 4.1 out of 1000 patients hospitalized for COVID-19. The majority of AM occurs in the absence of pneumonia and is often complicated by hemodynamic instability. AM is a rare complication in patients hospitalized for COVID-19, with an outcome that differs on the basis of the presence of concomitant pneumonia.

Heart transplantation (HTx) is a valid therapeutic option for end-stage heart failure secondary to cardiac sarcoidosis (CS) or giant-cell myocarditis (GCM). However, post-HTx outcomes in patients with inflammatory cardiomyopathy (ICM) have been poorly investigated. We searched PubMed, Scopus, Science Citation Index, EMBASE, and Google Scholar, screened the gray literature, and contacted experts in the field. We included studies comparing post-HTx survival, acute cellular rejection, and disease recurrence in patients with and without ICM. Data were synthesized by a random‐effects meta‐analysis. We screened 11,933 articles, of which 14 were considered eligible. In a pooled analysis, post-HTx survival was higher in CS than non-CS patients after 1 year (risk ratio [RR] 0.88, 95% confidence interval [CI] 0.60–1.17; I2 = 0%) and 5 years (RR 0.72, 95% CI 0.52–0.91; I2 = 0%), but statistically significant only after 5 years. During the first-year post-HTx, the risk of acute cellular rejection was similar for patients with and without CS, but after 5 years, it was lower in those with CS (RR 0.38, 95% CI 0.03–0.72; I2 = 0%). No difference in post-HTx survival was observed between patients with and without GCM after 1 year (RR 1.16, 95% CI 0.05–2.28; I2 = 0%) or 5 years (RR 0.98, 95% CI 0.42–1.54; I2 = 0%). During post-HTx follow-up, recurrence of CS and GCM occurred in 5% and 8% of patients, respectively. Post-HTx outcomes in patients with CS and GCM are comparable with cardiac recipients with other heart failure etiologies. Patients with ICM should not be disqualified from HTx. Graphic abstract

Aims The present study was done to assess the role of sudden cardiac death (SCD) among the presenting manifestations of and fatalities from cardiac sarcoidosis (CS). Methods and results We analysed altogether 351 cases of CS presenting from year 1998 through 2015 in Finland. There were 262 patients with a clinical diagnosis and treatment of CS, 27 patients with an initial lifetime diagnosis of giant cell myocarditis that was later converted to CS, and 62 cases detected at autopsy and identified by screening >820 000 death certificates from the national cause-of-death registry. The total case series comprised 253 females and 98 males aged on average 52 years at presentation. High-grade atrioventricular block was the most common first sign of CS (n = 147, 42%) followed by heart failure (n = 58, 17%), unexpected fatal (n = 38) or aborted (n = 12) SCD (14%), and sustained ventricular tachycardia (n = 48, 14%). Severe coronary artery disease was found at autopsy concomitant with CS in four of the 38 cases presenting with fatal SCD. Of all deaths recorded till the end of 2015, 64% (n = 54/84) were unexpected SCDs from CS that had either been silent during life or defied all attempts at diagnosis. The Kaplan–Meier estimate (95% CI) of survival from symptom onset was 85% (80–90%) at 5 years and 76% (68–84%) at 10 years. Conclusion Together fatal and aborted SCD constitute 14% of the presenting manifestations of CS. Nearly two-thirds of all fatalities from CS are caused by undiagnosed granulomas in the heart.

Objectives: To determine the anti-inflammatory effect and safety of hydroxychloroquine after acute myocardial infarction. Method: In this multicenter, double-blind, placebo-controlled OXI trial, 125 myocardial infarction patients were randomized at a median of 43 h after hospitalization to receive hydroxychloroquine 300 mg (n = 64) or placebo (n = 61) once daily for 6 months and, followed for an average of 32 months. Laboratory values were measured at baseline, 1, 6, and 12 months. Results: The levels of interleukin-6 (IL-6) were comparable at baseline between study groups (p = 0.18). At six months, the IL-6 levels were lower in the hydroxychloroquine group (p = 0.042, between groups), and in the on-treatment analysis, the difference at this time point was even more pronounced (p = 0.019, respectively). The high-sensitivity C-reactive protein levels did not differ significantly between study groups at any time points. Eleven patients in the hydroxychloroquine group and four in the placebo group had adverse events leading to in-terruption or withdrawal of study medication, none of which was serious (p = 0.10, between groups). Conclusions: In patients with myocardial infarction, hydroxychloroquine reduced IL-6 levels significantly more than did placebo without causing any clinically significant adverse events. A larger randomized clinical trial is warranted to prove the potential ability of hydroxychloroquine to reduce cardiovascular endpoints after myocar-dial infarction. (c) 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).

Heart transplantation (HTx) for patients with “giant cell myocarditis” (GCM) or “cardiac sarcoidosis” (CS) is still controversial. However, no single center has accumulated enough experience to investigate post-HTx outcome. The primary aim of this systematic review is to identify, appraise, and synthesize existing literature investigating whether patients who have undergone HTx because of GCM or CS have worse outcomes as compared with patients transplanted because of other etiologies. A systematic and comprehensive search will be performed using PubMed, Scopus, Web of Science, EMBASE, and Google Scholar, for studies published up to December 2019. Observational and interventional population-based studies will be eligible for inclusion. The quality of observational studies will be assessed using the Newcastle–Ottawa scale, while the interventional studies will be assessed using the Cochrane Effective Practice Organization of Care tool. The collected evidence will be narratively synthesized; in addition, we will perform a meta-analysis to pool estimates from studies considered to be homogenous. Reporting of the systematic review and meta-analysis will be in accordance with the Meta-analysis of Observational Studies in Epidemiology Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines. To our knowledge, this will be the first synthesis of outcomes, including survival, acute cellular rejection, and disease recurrence, in patients with either GCM or CS treated with HTx. Reviewing the suitability of HTx in this population and highlighting areas for further research will benefit both patients and healthcare providers. Trial registration: CRD42019140574.

Supplemental Digital Content is available in the text., Myocarditis is an inflammatory disease of the heart that may occur because of infections, immune system activation, or exposure to drugs. The diagnosis of myocarditis has changed due to the introduction of cardiac magnetic resonance imaging. We present an expert consensus document aimed to summarize the common terminology related to myocarditis meanwhile highlighting some areas of controversies and uncertainties and the unmet clinical needs. In fact, controversies persist regarding mechanisms that determine the transition from the initial trigger to myocardial inflammation and from acute myocardial damage to chronic ventricular dysfunction. It is still uncertain which viruses (besides enteroviruses) cause direct tissue damage, act as triggers for immune-mediated damage, or both. Regarding terminology, myocarditis can be characterized according to etiology, phase, and severity of the disease, predominant symptoms, and pathological findings. Clinically, acute myocarditis (AM) implies a short time elapsed from the onset of symptoms and diagnosis (generally

Background: Symptomatic high-grade atrioventricular block (AVB) is the most common and often the only presenting manifestation (lone AVB) of cardiac sarcoidosis. Implantation of an intracardiac cardioverter defibrillator instead of a pacemaker is recommended, but the true risk of fatal arrhythmia, one incident to lone AVB in particular, remains poorly known. Methods: We used Myocardial Inflammatory Diseases in Finland Study Group Registry to analyze the presentations, left ventricular (LV) function, pacemaker therapy, and ventricular arrhythmias in cardiac sarcoidosis. From year 1988 to 2015, altogether 325 cases of cardiac sarcoidosis were diagnosed in Finland. Of them, 143 patients (112 women, mean age 52 years) presented with Mobitz II second degree or third degree AVB in the absence of other explanatory cardiac disease. Results: Concomitant with AVB at presentation, 20 patients had either ventricular tachycardia or severe LV dysfunction with ejection fraction P =0.019). The 5-year incidence of sudden cardiac death was 34% (16%–71%), 14% (6%–35%), and 9% (4%–22%) in the respective subgroups ( P =0.060). Conclusions: The risk of sudden cardiac death is significant in cardiac sarcoidosis presenting with high-grade AVB with or without ventricular tachycardia or LV dysfunction. The consensus recommendation to implant an intracardiac cardioverter defibrillator whenever permanent pacing is needed seems well-founded.

Aims The value of single-photon emission tomography (SPECT) in patients with severe chronic kidney disease is controversial, and the implications of SPECT finding with lower level of ischaemia are unknown. We assessed the prognostic value of SPECT in patients evaluated for kidney transplantation. Methods and results Five hundred and forty-eight patients underwent SPECT as a part of routine evaluation for kidney transplantation. During the median follow-up of 43.7 months (IQR 22.4-68.4 months), 112 patients (20.4%) died, 49 of cardiovascular (CV) causes (8.9%). In comparison to those with no perfusion defects, mild perfusion abnormalities (1%-9.9%) had an adjusted Cox hazard ratio (HR) of 1.80 [95% confidence interval (95% CI) 1.02-3.17, P = 0.041] for all-cause mortality, while large perfusion defects (≥10%) demonstrated an HR of 2.20 (95% CI 1.38-3.50, P = 0.001). A competing risk analysis produced a similar prognostic capacity for CV mortality. SPECT also offered incremental prognostic impact with two reclassification methods. Revascularization was performed clearly more often on patients with severely than mildly abnormal or normal SPECT (28.0%, 4.3%, and 1.3%, respectively, P

Myocarditis is a diverse group of heart-specific immune processes classified by clinical and histopathological manifestations. Up to 40% of dilated cardiomyopathy is associated with inflammation or viral infection. Recent experimental studies revealed complex regulatory roles for several microribonucleic acids and T-cell and macrophage subtypes. Although the prevalence of myocarditis remained stable between 1990 and 2013 at about 22 per 100,000 people, overall mortality from cardiomyopathy and myocarditis has decreased since 2005. The diagnostic and prognostic value of cardiac magnetic resonance has increased with new, higher-sensitivity sequences. Positron emission tomography has emerged as a useful tool for diagnosis of cardiac sarcoidosis. The sensitivity of endomyocardial biopsy may be increased, especially in suspected sarcoidosis, by the use of electrogram guidance to target regions of abnormal signal. Investigational treatments on the basis of mechanistic advances are entering clinical trials. Revised management recommendations regarding athletic participation after acute myocarditis have heightened the importance of early diagnosis.

Evaluation and treatment of cardiac sarcoidosis (CS) suffer from lack of sensitive and easily repeatable markers of disease activity. We studied measurements of high-sensitivity cardiac troponin T or troponin I (hs-cTnT/I) taken at presentation and during treatment in 62 patients with new-onset CS (48 women, mean age 49 years). Hs-cTnT was measured in 50 patients and was elevated (13 ng/L) at presentation in 26 of them (52%). Hs-cTnI was measured in the remaining 12 patients and was elevated (0.04 ng/mL) in 7 of them (58%). Left ventricular ejection fraction averaged 43 ± 14% in association with elevated hs-cTnT/I (n = 33) versus 53 ± 10% with normal hs-cTnT/I (n = 29; p = 0.001). Hs-cTnT/I was remeasured after 4 weeks of steroid therapy in 38 patients and was normalized in 16 of the 24 (67%) with an elevated pretreatment concentration and remained normal in the rest of the 14 patients (p0.001). During follow-up (median, 17 months), cardiac death (n = 2), aborted sudden death (n = 5), sustained ventricular tachycardia (n = 8), or new complete atrioventricular block (n = 1) was recorded in 11 of 33 patients with elevated hs-cTnT/I versus in 5 of 29 with normal hs-cTnT/I (log-rank p = 0.068). Two-year event-free Kaplan-Meier cardiac survival estimate (95% confidence interval) was 67% (48% to 81%) with elevated hs-cTnT/I versus 93% (76% to 99%) with normal hs-cTnT/I. In CS, circulating hs-cTnT/I may help clinicians evaluate disease activity and treatment response. Their prognostic value remains tentative pending more follow-up data.

Background Inflammation of the arterial wall plays a central role in the pathogenesis of atherosclerosis. Among patients with rheumatic diseases, anti-rheumatic medication reduces the incidence of cardiovascular (CV) diseases, but only few studies have addressed their cardioprotective effects on patients with no rheumatic diseases. Hydroxychloroquine (HCQ) is an anti-rheumatic drug commonly used in the treatment of rheumatoid arthritis and systemic lupus erythematosus. In addition to its anti-inflammatory properties, HCQ reduces cholesterol levels and the risk of type II diabetes, and has also anti-platelet effects. Design The OXI trial is an event-driven trial that will randomize 2500 patients hospitalized for myocardial infarction (MI). Participants will receive active HCQ or placebo for at least 12 months, and until 350 CV events are confirmed. The primary trial endpoint is the composite of death, MI, hospitalization for unstable angina, urgent percutaneous coronary intervention, and urgent coronary artery bypass grafting. Secondary trial endpoints are the primary end point plus stroke, the effect of HCQ treatment on lipids, on the incidence of Type 2 diabetes, on the level of haemoglobin A1c, and on inflammatory parameters. A 6 months placebo-controlled safety pilot trial with 200 patients is currently ongoing to assess the safety of HCQ in the setting of MI. Summary The OXI trial will determine whether treatment with HCQ, as compared with placebo, will reduce recurrent CV events among MI patients. If positive, then the OXI trial would provide an entirely novel multitarget approach for the secondary prevention of atherosclerotic cardiovascular diseases (ACVD).

Abstract —Angiotensin II type 2 (AT 2 ) receptor exerts an inhibitory action on cell growth. In the present study, we report that the stimulation of AT 2 receptor in AT 2 receptor cDNA–transfected rat adult vascular smooth muscle cells (VSMCs) inhibited angiotensin II type 1 (AT 1 ) receptor–mediated tyrosine phosphorylation of STAT (signal transducers and activators of transcription) 1α/β, STAT2, and STAT3 without influence on Janus kinase. AT 2 receptor activation also inhibited the tyrosine phosphorylation of STAT1α/β induced by interferon-γ, epidermal growth factor, and platelet-derived growth factor. Similar effects of AT 2 receptor were observed in R3T3 fibroblast and mouse fetal VSMCs, which express endogenous AT 2 receptor. Moreover, AT 2 receptor inhibited serine phosphorylation of STAT1α and STAT3 via the inhibition of extracellular signal–regulated kinase (ERK) activation. Stimulation of AT 2 receptor inhibited the binding of STATs with sis -inducing element in c- fos promoter, resulting in decreased c- fos expression. Taken together, our results suggest that AT 2 receptor can crosstalk negatively with multiple families of growth receptors by inhibiting ERK and STAT activation.

A 48-year-old male patient presented with dyspnea on exertion. Patient was found to have pulmonary hypertension. Myocardial biopsy showed amyloidosis and further work-up revealed Salmon-Durie stage 1A multiple myeloma. Patient had no other clinical manifestations of amyloidosis. It is possible that the pulmonary hypertension is caused by amyloid deposition into pulmonary arteries as the arterial amyloid deposition is common in AL amyloidosis. Treatment with sildenafil led to hemodynamic and symptomatic improvement.