Lymphocytic Perimyocarditis Masquerading as Steroid-Dependent Recurrent Pericarditis.

Lymphocytic myocarditis is a pattern of myocardial inflammation typically associated with viral, autoimmune, or idiopathic causes. We present a case of lymphocytic perimyocarditis masquerading as steroid-dependent recurrent pericarditis. This case shows the advantages of using multimodal cardiac imaging and endomyocardial biopsy in clarifying diagnosis in treatment-resistant cases. (Level of Difficulty: Advanced.).

Advances in multi-modality imaging for constrictive pericarditis and pericardial inflammation: role of imaging-guided therapy.

INTRODUCTION: Constrictive pericarditis (CP) can result from uncontrolled inflammation of the pericardium. This can be due to various etiologies. CP can lead to both left- and right-sided heart failure with associated poor quality of life, so early recognition is key. The evolving role of multimodality cardiac imaging allows for earlier diagnosis and facilitates management to help mitigate this adverse outcome. AREAS COVERED: This review discusses the pathophysiology of constrictive pericarditis, chronic inflammation and autoimmune etiologies, clinical presentation of CP, and advances in multimodality cardiac imaging for diagnosis and management. Echocardiography and cardiac magnetic resonance (CMR) imaging remain cornerstone modalities to evaluate this condition, whereas additional imaging modalities such as computed tomography and FDG-positron emission tomography can provide complementary information. EXPERT OPINION: Advances in multimodality imaging allow for a more precision diagnosis of constrictive pericarditis. There has been a paradigm shift in pericardial disease management with advances in multimodality imaging, especially CMR, to detect subacute and chronic inflammation. This has enabled imaging-guided therapy (IGT) to both help prevent and potentially reverse established constrictive pericarditis.

Contemporary Review of Multi-Modality Cardiac Imaging Evaluation of Infective Endocarditis.

Infective endocarditis (IE) remains to be a heterogeneous disease with high morbidity and mortality rates, which can affect native valves, prosthetic valves, and intra-cardiac devices, in addition to causing systemic complications. The combination of clinical, laboratory, and cardiac imaging evaluation is critical for early diagnosis and risk stratification of IE. This can facilitate timely medical and surgical management to improve patient outcomes. Key imaging findings for IE include vegetations, valve perforation, prosthetic valve dehiscence, pseudoaneurysms, abscesses, and fistulae. Transthoracic echocardiography continues to be the first-line imaging modality of choice, while transesophageal echocardiography subsequently provides an improved structural assessment and characterization of lesions to facilitate management decision in IE. Recent advances in other imaging modalities, especially cardiac computed tomography and 18F-fluorodeox-yglucose positron emission tomography, and to a lesser extent cardiac magnetic resonance imaging and other nuclear imaging techniques, have demonstrated important roles in providing complementary IE diagnostic and prognostic information. This review aims to discuss the individual and integrated utilities of contemporary multi-modality cardiac imaging for the assessment and treatment guidance of IE.

The COVID-19 Pandemic and Adult Cardiac Transplantation: Impact, Interventions, and Implications.

In this review, we provide a comprehensive overview of the impact of the COVID-19 pandemic on adult heart transplantation. We highlight the decline in the number of adult transplantations performed throughout the pandemic as a consequence of restrictions imposed on individual programs and hospitals. There were challenges to maintaining cardiac transplant activity at multiple levels, including organ donation in intensive care units, logistical difficulties with organ procurement, and rapidly changing resource considerations at health system and jurisdictional levels. We also review the impact of COVID-19 on cardiac transplant recipients. Despite the high rates of morbidity and mortality observed during the initial phases of the pandemic among heart transplant patients infected with COVID-19, the availability of effective vaccines, pre-exposure prophylaxis, and specific antiviral therapies have drastically improved outcomes over time. Vaccines have proven to be safe and effective in reducing infections and illness severity, but specific considerations in the immunocompromised solid organ transplant population apply, including the need for additional booster doses to achieve sufficient immunisation. We further outline the strong rationale for vaccination before transplantation wherever possible. Finally, the COVID-19 response created a number of barriers to safe and efficient post-transplantation care. Given the need for frequent evaluation and monitoring, especially in the first several months after cardiac transplantation, the pandemic provided the impetus to improve virtual care delivery and explore noninvasive rejection surveillance through gene expression profiling. We hope that lessons learned will allow us to prepare and pivot effectively during future pandemics and health care emergencies.

Imaging for Cardiovascular Complications of COVID-19: Cardiac Manifestations in Context.

After the first confirmed case in 2019, COVID-19 rapidly spread worldwide and overwhelmed the medical community. In the intervening time, we have learned about COVID-19's clinical manifestations and have developed effective therapies and preventative vaccines. Severe COVID-19 infection is associated with many cardiovascular disorders in the acute phase, and patients recovered from illness can also manifest long-term sequelae, including long COVID syndrome. Furthermore, severe acute respiratory syndrome-related coronavirus-2 messenger RNA (mRNA) vaccination can trigger rare cases of myopericarditis. We have gained significant knowledge of the acute and long-term cardiovascular complications of COVID-19- and mRNA vaccine-associated myocarditis through clinical and investigative studies using cardiac imaging. In this review, we describe how cardiovascular imaging can be used to understand the cardiovascular complications and cardiac injury associated with acute COVID-19 infection, review the imaging findings in patients recovered from illness, and discuss the role and limitations of cardiac imaging in COVID-19 mRNA vaccine-associated myocarditis.

Aggressive Cholesterol Pericarditis With Minimal Effusion Masquerading as Treatment-Refractory Autoimmune Disease.

A middle-aged woman with rheumatoid arthritis presented with treatment-refractory pericarditis. Symptoms persisted despite escalation of immunosuppression, and she had recurrent admissions for heart failure. Imaging revealed minimal pericardial effusion and a thickened pericardium. Invasive hemodynamics confirmed constrictive physiology, and a pericardiectomy was required. Pathology testing confirmed cholesterol pericarditis, a rare condition of inflammatory cholesterol deposits within the pericardium. Previous reports describe moderate-to-large volumes of gold-coloured pericardial fluid. This case illustrates that cholesterol pericarditis can present with minimal pericardial effusion and rapidly progress to pericardial constriction.

Une femme d'âge moyen atteinte d'arthrite rhumatoïde a présenté une péricardite réfractaire. Les symptômes ont persisté en dépit de l'escalade de l'immunodépression. Elle a été admise de façon répétitive en raison d'insuffisance cardiaque. L'imagerie a révélé un épanchement péricardique minimal et un péricarde épaissi. L'exploration hémodynamique invasive a permis de confirmer la physiologie constrictive. Une péricardectomie a été nécessaire. L'examen pathologique a permis de confirmer la péricardite cholestérolique, une affection inflammatoire rare due aux dépôts de cholestérol dans le péricarde. Les observations précédentes décrivent des volumes modérés à élevés de liquide péricardique doré. Ce cas illustre que la péricardite cholestérolique peut se traduire par un épanchement péricardique minimal et progresser rapidement vers la péricardite constrictive.

Features of Inflammatory Heart Reactions Following mRNA COVID-19 Vaccination at a Global Level.

Myocarditis and pericarditis may constitute adverse reactions of mRNA coronavirus disease 2019 (COVID-19) vaccines. This study aimed to document these reactions and to assess the association with patient sex and age. This is as an observational retrospective study using a case-non-case design (also called disproportionality study) on inflammatory heart reactions reported with mRNA COVID-19 vaccines within the World Health Organization (WHO) global safety database (VigiBase), up to June 30, 2021. Results are expressed using reporting odds ratios (RORs) and their 95% confidence interval (95% CI). Of 716,576 reports related to mRNA COVID-19 vaccines, 2,277 were cases of inflammatory heart reactions, including 1241 (55%) myocarditis and 851 (37%) pericarditis. The main age group was 18-29 years (704, 31%), and mostly male patients (1,555, 68%). Pericarditis onset was delayed compared with myocarditis with a median time to onset of 8 (3-21) vs. 3 (2-6) days, respectively (P = 0.001). Regarding myocarditis, an important disproportionate reporting was observed in adolescents (ROR, 22.3, 95% CI 19.2-25.9) and in 18-29 years old (ROR, 6.6, 95% CI 5.9-7.5) compared with older patients, as well as in male patients (ROR, 9.4, 95% CI 8.3-10.6). Reporting rate of myocarditis was increased in young adults and adolescents. Inflammatory heart reactions may rarely occur shortly following mRNA COVID-19 vaccination. Although an important disproportionate reporting of myocarditis was observed among adolescents and young adults, particularly in male patients, reporting rates support a very rare risk, that does not seem to compromise the largely positive benefit-risk balance of these vaccines. Furthermore, this study confirmed the value of disproportionality analyses for estimation of relative risks among subgroups of patients.

Multimodality Imaging in Transcatheter Mitral Interventions.

Multimodality imaging is of imperative value for the planning and guidance of transcatheter mitral valve interventions. This review employs the value of different imaging modalities and future implications for clinical practice.

Cannabis for the Treatment of Crohn's Disease and Ulcerative Colitis: Evidence From Cochrane Reviews.

BACKGROUND: We systematically reviewed the safety and effectiveness of cannabis and cannabinoids treatment for Crohn's disease (CD) and ulcerative colitis (UC). METHODS: MEDLINE, Embase, WHO ICTRP, AMED, PsychINFO, CENTRAL, ClinicalTrials.Gov, and the European Clinical Trials Register were searched for relevant studies. MAIN RESULTS: Five randomized controlled trials (3 CD and 2 UC studies, 185 participants) were included. One CD study (N = 21) showed 45% (5 of 11) of the cannabis cigarette group experienced clinical remission compared with 10% (1 of 10) of the placebo group (risk ratio [RR] 4.55; 95% CI, 0.63-32.56). Another CD study (N = 19) did not show significant rates of clinical remission. Forty percent (4 of 10) of participants in the cannabis oil group experienced remission compared with 33% (3 of 9) of the placebo group (RR 1.20; 95% CI, 0.36-3.97). A UC study (N = 60) did not have significant clinical remission rates. Twenty-four percent (7 of 29) of cannabis oil participants experienced remission compared with 26% (8 of 31) of placebo participants (RR 0.94; 95% CI, 0.39-2.25). A second UC study (N = 32) showed the effects on disease activity, C-reactive protein levels, and fecal calprotectin levels were uncertain. Adverse events were more prevalent in the cannabis groups for both CD and UC studies. GRADE analysis for the UC and CD studies ranged from very low to moderate. CONCLUSIONS: In summary, no firm conclusions can be made regarding the safety and effectiveness of cannabis and cannabinoids in adults with CD and UC.

Cannabis for the treatment of ulcerative colitis.

BACKGROUND: Cannabis and cannabinoids are often promoted as treatment for many illnesses and are widely used among patients with ulcerative colitis (UC). Few studies have evaluated the use of these agents in UC. Further, cannabis has potential for adverse events and the long-term consequences of cannabis and cannabinoid use in UC are unknown. OBJECTIVES: To assess the efficacy and safety of cannabis and cannabinoids for the treatment of patients with UC. SEARCH METHODS: We searched MEDLINE, Embase, WHO ICTRP, AMED, PsychINFO, the Cochrane IBD Group Specialized Register, CENTRAL, ClinicalTrials.Gov and the European Clinical Trials Register from inception to 2 January 2018. Conference abstracts and references were searched to identify additional studies. SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing any form or dose of cannabis or its cannabinoid derivatives (natural or synthetic) to placebo or an active therapy for adults (> 18 years) with UC were included. DATA COLLECTION AND ANALYSIS: Two authors independently screened search results, extracted data and assessed bias using the Cochrane risk of bias tool. The primary outcomes were clinical remission and relapse (as defined by the primary studies). Secondary outcomes included clinical response, endoscopic remission, endoscopic response, histological response, quality of life, C-reactive protein (CRP) and fecal calprotectin measurements, symptom improvement, adverse events, serious adverse events, withdrawal due to adverse events, psychotropic adverse events, and cannabis dependence and withdrawal effects. We calculated the risk ratio (RR) and corresponding 95% confidence interval for dichotomous outcomes. For continuous outcomes, we calculated the mean difference (MD) and corresponding 95% CI. Data were pooled for analysis when the interventions, patient groups and outcomes were sufficiently similar (determined by consensus). Data were analyzed on an intention-to-treat basis. GRADE was used to evaluate the overall certainty of evidence. MAIN RESULTS: Two RCTs (92 participants) met the inclusion criteria. One study (N = 60) compared 10 weeks of cannabidiol capsules with up to 4.7% D9-tetrahydrocannabinol (THC) with placebo capsules in participants with mild to moderate UC. The starting dose of cannabidiol was 50 mg twice daily increasing to 250 mg twice daily if tolerated. Another study (N = 32) compared 8 weeks of therapy with two cannabis cigarettes per day containing 0.5 g of cannabis, corresponding to 23 mg THC/day to placebo cigarettes in participants with UC who did not respond to conventional medical treatment. No studies were identified that assessed cannabis therapy in quiescent UC. The first study was rated as low risk of bias and the second study (published as an abstract) was rated as high risk of bias for blinding of participants and personnel. The studies were not pooled due to differences in the interventional drug.The effect of cannabidiol capsules (100 mg to 500 mg daily) compared to placebo on clinical remission and response is uncertain. Clinical remission at 10 weeks was achieved by 24% (7/29) of the cannabidiol group compared to 26% (8/31) in the placebo group (RR 0.94, 95% CI 0.39 to 2.25; low certainty evidence). Clinical response at 10 weeks was achieved in 31% (9/29) of cannabidiol participants compared to 22% (7/31) of placebo patients (RR 1.37, 95% CI 0.59 to 3.21; low certainty evidence). Serum CRP levels were similar in both groups after 10 weeks of therapy. The mean CRP in the cannabidiol group was 9.428 mg/L compared to 7.638 mg/L in the placebo group (MD 1.79, 95% CI -5.67 to 9.25; moderate certainty evidence). There may be a clinically meaningful improvement in quality of life at 10 weeks, measured with the IBDQ scale (MD 17.4, 95% CI -3.45 to 38.25; moderate certainty evidence). Adverse events were more frequent in cannabidiol participants compared to placebo. One hundred per cent (29/29) of cannabidiol participants had an adverse event, compared to 77% (24/31) of placebo participants (RR 1.28, 95% CI 1.05 to1.56; moderate certainty evidence). However, these adverse events were considered to be mild or moderate in severity. Common adverse events included dizziness, disturbance in attention, headache, nausea and fatigue. None (0/29) of the cannabidiol participants had a serious adverse event compared to 13% (4/31) of placebo participants (RR 0.12, 95% CI 0.01 to 2.11; low certainty evidence). Serious adverse events in the placebo group included worsening of UC and one complicated pregnancy. These serious adverse events were thought to be unrelated to the study drug. More participants in the cannabidiol group withdrew due to an adverse event than placebo participants. Thirty-four per cent (10/29) of cannabidiol participants withdrew due to an adverse event compared to 16% (5/31) of placebo participants (RR 2.14, 95% CI 0.83 to 5.51; low certainty evidence). Withdrawls in the cannabidiol group were mostly due to dizziness. Withdrawals in the placebo group were due to worsening UC.The effect of cannabis cigarettes (23 mg THC/day) compared to placebo on mean disease activity, CRP levels and mean fecal calprotectin levels is uncertain. After 8 weeks, the mean disease activity index score in cannabis participants was 4 compared with 8 in placebo participants (MD -4.00, 95% CI -5.98 to -2.02). After 8 weeks, the mean change in CRP levels was similar in both groups (MD -0.30, 95% CI -1.35 to 0.75; low certainty evidence). The mean fecal calprotectin level in cannabis participants was 115 mg/dl compared to 229 mg/dl in placebo participants (MD -114.00, 95% CI -246.01 to 18.01). No serious adverse events were observed. This study did not report on clinical remission, clinical response, quality of life, adverse events or withdrawal due to adverse events. AUTHORS' CONCLUSIONS: The effects of cannabis and cannabidiol on UC are uncertain, thus no firm conclusions regarding the efficacy and safety of cannabis or cannabidiol in adults with active UC can be drawn.There is no evidence for cannabis or cannabinoid use for maintenance of remission in UC. Further studies with a larger number of patients are required to assess the effects of cannabis in UC patients with active and quiescent disease. Different doses of cannabis and routes of administration should be investigated. Lastly, follow-up is needed to assess the long term safety outcomes of frequent cannabis use.

Cannabis for the treatment of Crohn's disease.

BACKGROUND: Crohn's disease (CD) is a chronic immune-mediated condition of transmural inflammation in the gastrointestinal tract, associated with significant morbidity and decreased quality of life. The endocannabinoid system provides a potential therapeutic target for cannabis and cannabinoids and animal models have shown benefit in decreasing inflammation. However, there is also evidence to suggest transient adverse events such as weakness, dizziness and diarrhea, and an increased risk of surgery in people with CD who use cannabis. OBJECTIVES: The objectives were to assess the efficacy and safety of cannabis and cannabinoids for induction and maintenance of remission in people with CD. SEARCH METHODS: We searched MEDLINE, Embase, AMED, PsychINFO, the Cochrane IBD Group Specialized Register, CENTRAL, ClinicalTrials.Gov, and the European Clinical Trials Register up to 17 October 2018. We searched conference abstracts, references and we also contacted researchers in this field for upcoming publications. SELECTION CRITERIA: Randomized controlled trials comparing any form of cannabis or its cannabinoid derivatives (natural or synthetic) to placebo or an active therapy for adults with Crohn's disease were included. DATA COLLECTION AND ANALYSIS: Two authors independently screened search results, extracted data and assessed bias using the Cochrane risk of bias tool. The primary outcomes were clinical remission and relapse. Remission is commonly defined as a Crohn's disease activity index (CDAI) of < 150. Relapse is defined as a CDAI > 150. Secondary outcomes included clinical response, endoscopic remission, endoscopic improvement, histological improvement, quality of life, C-reactive protein (CRP) and fecal calprotectin measurements, adverse events (AEs), serious AEs, withdrawal due to AEs, and cannabis dependence and withdrawal effects. We calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI) for dichotomous outcomes. For continuous outcomes, we calculated the mean difference (MD) and 95% CI. Data were combined for analysis when the interventions, patient groups and outcomes were sufficiently similar (determined by consensus). Data were analyzed on an intention-to-treat basis and the overall certainty of the evidence supporting the outcomes was evaluated using the GRADE criteria. MAIN RESULTS: Three studies (93 participants) that assessed cannabis in people with active CD met the inclusion criteria. One ongoing study was also identified. Participants in two of the studies were adults with active Crohn's disease who had failed at least one medical treatment. The inclusion criteria for the third study were unclear. No studies that assessed cannabis therapy in quiescent CD were identified. The studies were not pooled due to differences in the interventional drug.One small study (N = 21) compared eight weeks of treatment with cannabis cigarettes containing 115 mg of D9-tetrahydrocannabinol (THC) to placebo cigarettes containing cannabis with the THC removed in participants with active CD. This study was rated as high risk of bias for blinding and other bias (cannabis participants were older than placebo). The effects of cannabis on clinical remission were unclear. Forty-five per cent (5/11) of the cannabis group achieved clinical remission compared with 10% (1/10) of the placebo group (RR 4.55, 95% CI 0.63 to 32.56; very low certainty evidence). A difference was observed in clinical response (decrease in CDAI score of >100 points) rates. Ninety-one per cent (10/11) of the cannabis group achieved a clinical response compared to 40% (4/10) of the placebo group (RR 2.27, 95% CI 1.04 to 4.97; very low certainty evidence). More AEs were observed in the cannabis cigarette group compared to placebo (RR 4.09, 95% CI 1.15 to 14.57; very low certainty evidence). These AEs were considered to be mild in nature and included sleepiness, nausea, difficulty with concentration, memory loss, confusion and dizziness. This study did not report on serious AEs or withdrawal due to AEs.One small study (N = 22) compared cannabis oil (5% cannabidiol) to placebo oil in people with active CD. This study was rated as high risk of bias for other bias (cannabis participants were more likely than placebo participants to be smokers). There was no difference in clinical remission rates. Forty per cent (4/10) of cannabis oil participants achieved remission at 8 weeks compared to 33% (3/9) of the placebo participants (RR 1.20, 95% CI 0.36 to 3.97; very low certainty evidence). There was no difference in the proportion of participants who had a serious adverse event. Ten per cent (1/10) of participants in the cannabis oil group had a serious adverse event compared to 11% (1/9) of placebo participants (RR 0.90, 95% CI 0.07 to 12.38, very low certainty evidence). Both serious AEs were worsening Crohn's disease that required rescue intervention. This study did not report on clinical response, CRP, quality of life or withdrawal due to AEs.One small study (N= 50) compared cannabis oil (15% cannabidiol and 4% THC) to placebo in participants with active CD. This study was rated as low risk of bias. Differences in CDAI and quality of life scores measured by the SF-36 instrument were observed. The mean quality of life score after 8 weeks of treatment was 96.3 in the cannabis oil group compared to 79.9 in the placebo group (MD 16.40, 95% CI 5.72 to 27.08, low certainty evidence). After 8 weeks of treatment, the mean CDAI score was118.6 in the cannabis oil group compared to 212.6 in the placebo group (MD -94.00, 95%CI -148.86 to -39.14, low certainty evidence). This study did not report on clinical remission, clinical response, CRP or AEs. AUTHORS' CONCLUSIONS: The effects of cannabis and cannabis oil on Crohn's disease are uncertain. Thus no firm conclusions regarding the efficacy and safety of cannabis and cannabis oil in adults with active Crohn's disease can be drawn. The effects of cannabis or cannabis oil in quiescent Crohn's disease have not been investigated. Further studies with larger numbers of participants are required to assess the potential benefits and harms of cannabis in Crohn's disease. Future studies should assess the effects of cannabis in people with active and quiescent Crohn's disease. Different doses of cannabis and delivery modalities should be investigated.