The Association and Utility of Left Ventricular End-Diastolic Pressure in Predicting the Development of and in Managing Contrast-Induced Nephropathy in Patients Undergoing Coronary Angiography.

Contrast-induced nephropathy (CIN) is a significant complication in patients undergoing coronary angiography, and its development is associated with increased morbidity and mortality. Left ventricular end-diastolic pressure (LVEDP) provides one index of left heart filling status. An elevated LVEDP can reflect volume overload or abnormal diastolic function and indicates a cardiac disorder. Data on the association between an elevated LVEDP and CIN are limited and have had conflicting results. We systematically searched the databases PubMed, Embase, and Scopus for full-text articles from database inception to May 2022. Studies were included if they evaluated the association between a high LVEDP and the incidence of CIN in patients undergoing coronary angiography. The study was registered in the PROSPERO CRD42022334070. A second search in PubMed identified randomized controlled trials using LVEDP to guide fluid administration during coronary procedures. Four studies were identified that used LVEDP to classify patients into groups to determine the association between the level and the development of CIN. In these studies, 240 patients of 2441 patients (9.8%) developed CIN. One study found no association between LVEDP levels and the development of CIN. Two studies found an increased frequency of CIN in patients with elevated levels using 2 cutoff points for LVEDP, ≥20 mm Hg and >30 mm Hg. One study found that lower LVEDP levels (5-14 mm Hg) were associated with the development of CIN. Three randomized control trials used LVDEP levels to manage fluid administration in patients undergoing coronary procedures; only one study found that the use of these levels to guide fluid administration resulted in better outcomes. In patients undergoing coronary angiography, an elevated LVEDP was not consistently associated with increased risk of CIN, and using LVEDP levels to guide fluid administration during these procedures did not always improve outcomes in comparison to other protocols. The use of LVEDP levels can help classify patients with cardiac disorders but does not necessarily provide an adequate description of the hemodynamic patterns in these patients to predict or prevent CIN in patients undergoing angiography.

Pulmonary artery aneurysm in a young female with Takayasu arteritis.

Key Clinical Message: In suspected cases of systemic vasculitis, imaging studies should include the pulmonary artery. This is a rare case of Takayasu arteritis with a large pulmonary aneurysm. Medical management is the first line and vascular intervention if fails prior. Abstract: Takayasu arteritis (TA) should be suspected in young women presented with hypertension, carotidynia, and claudications. Pulmonary artery involvement is frequent, occurring in 20%-50% of patients with TA. However, this case highlights the rare presentation of TA with a large pulmonary aneurysm and minimal aortic involvement. Medical management including immunosuppressive agents and biological therapies remains an important role, with vascular intervention remains as an option if medical therapy failed.

High-risk phenotypes of arrhythmic mitral valve prolapse: a systematic review and meta-analysis.

BACKGROUND: Mitral valve prolapse (MVP) is associated with aggravated risk of ventricular tachycardia (VT), ventricular fibrillation (VF) and sudden cardiac death (SCD). There is a lack of specific guideline recommendation regarding risk stratification and management, despite multiple proposed high-risk phenotypes. We performed systematic review and meta-analysis to evaluate high-risk phenotypes for malignant arrhythmias in patients with MVP. METHODS: We comprehensively searched the databases of MEDLINE, SCOPUS, and EMBASE from inception to April 2023. Included studies were cohort and case-control comparing between MVP patients with and without VT, VF, cardiac arrest, ICD placement, or SCD. Data from each study were combined using the random-effects. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated. RESULTS: Nine studies from 1985 to 2023 were included involving 2,279 patients with MVP. We found that T-wave inversion (OR 2.52; 95% CI: 1.90-3.33; p < 0.001), bileaflet involvement (OR 2.28; 95% CI: 1.69-3.09; p < 0.001), late gadolinium enhancement (OR 17.05; 95% CI: 3.41-85.22; p < 0.001), mitral annular disjunction (OR 3.71; 95% CI: 1.63-8.41; p < 0.002), and history of syncope (OR 6.96; 95% CI: 1.05-46.01; p = 0.044), but not female (OR 0.96; 95% CI: 0.46-2.01; p = 0.911), redundant leaflets (OR 4.30; 95% CI: 0.81-22.84; p = 0.087), or moderate-to-severe mitral regurgitation (OR 1.24; 95% CI: 0.65-2.37; p = 0.505), were associated with those events. CONCLUSION: Bileaflet prolapse, T-wave inversion, mitral annular disjunction, late gadolinium enhancement, and history of syncope are high-risk phenotypes among population with MVP. Further research is needed to validate the risk stratification model and justify the role of primary prophylaxis against malignant arrhythmias.

Association between elevated CHA2DS2-VASC score and contrast-induced nephropathy among patients undergoing percutaneous coronary intervention: a systematic review and meta-analysis.

BACKGROUND: Promising results with the CHA2DS2-VASc risk score (CVRS) have been reported for the prediction of contrast-induced nephropathy (CIN). The aim of this study is to consolidate all the data available and examine the association between elevated CVRS and the incidence of CIN in patients undergoing percutaneous coronary intervention (PCI). METHODS: We systematically searched PubMed, Embase, and Scopus for abstracts and full-text articles from inception to May 2022. Studies were included if they evaluated the association between a high CVRS and the incidence of CIN in patients undergoing PCI. Data were integrated using the random-effects, generic inverse variance method of DerSimonian and Laird. Prospero registration: CRD42022334065. RESULTS: Seven studies from 2016 to 2021 with a total of 7,401 patients were included. In patients undergoing PCI, a high CVRS (≥2: Odds ratio [OR]:2.98, 95% confidence interval [95% CI] 2.25-3.94, p < .01, I2 = 1%, ≥3: OR 4.46, 95% CI 2.27-8.78, p < .01, I2=56% and ≥4: OR:2.75, 95% CI 1.76-4.30, p < .01, I2 = 11%) was significantly associated with an increase incidence for CIN. Subgroup analyses were done in patients with acute coronary syndrome, and association with CIN remained statistically significant (≥2: OR 2.93, 95% CI 2.11-4.07, p < .01, I2=22%and ≥4: OR:2.24, 95% CI 1.36-3.69, p < .01, I2 = 0%,). CONCLUSION: In patients undergoing PCI, an elevated CVRS is associated with an increased risk for CIN. More rigorous studies are needed to clarify this association and to identify strategies to reduce CIN.

CARDIOGENIC SHOCK ASSOCIATED WITH ACUTE NOROVIRUS GASTROENTERITIS: WHAT IS NEEDED TO PROVE CAUSALITY?

Acute myocarditis is a well-recognized condition attributable to a variety of viral illnesses. Common viral aetiologies include enteroviruses including coxsackie, adenovirus, influenza, echovirus, parvovirus B19 and herpesvirus. A high index of suspicion, early diagnosis, and prompt management with supportive anti-failure measures, and in selected cases immunosuppressive therapies including high-dose steroids, might be considered for better outcomes. The authors report a case of sudden onset of acute heart failure complicated by cardiogenic shock caused by viral myocarditis in a patient who initially presented with norovirus gastroenteritis. She had no previous cardiac history or significant cardiovascular risk factors. Prompt medical management for cardiogenic shock for norovirus-induced myocarditis was started, her symptoms gradually improved, and she was discharged safely on regular follow-up. LEARNING POINTS: Viral myocarditis exhibits a wide spectrum of symptoms ranging from non-specific prodromes such as fatigue and myalgia to chest pain, life-threatening arrhythmias, fulminant heart failure, or even sudden cardiac death.Common viral aetiologies for myocarditis include enteroviruses including coxsackie, adenovirus, influenza, echovirus, parvovirus B19 and herpesvirus.A high index of suspicion, early diagnosis, and prompt management with supportive anti-failure measures, and in selected cases immunosuppressive therapies including high-dose steroids, might be considered for better outcomes in cases of acute myocarditis.

Transient diabetes insipidus after vasopressin discontinuation in cystic fibrosis with septic shock.

Central diabetes insipidus (DI) is an uncommon condition caused by reduced or lack of vasopressin secretion from the posterior pituitary gland, typically caused by gland destruction. Several other causes for central DI have also been proposed. Here we present a case of transient central DI after discontinuation of vasopressin used for septic shock without evidence of overt pituitary damage in a cystic fibrosis patient. The serum sodium concentration peaked at 137 mmol/L in the setting of polyuria within 3 days of vasopressin discontinuation without other identified alternative etiologies. Sodium levels and urine output trended down dramatically with desmopressin administration.

Cardiac amyloidosis-An underdiagnosed cause of heart failure: A case report and review of literature.

Restrictive cardiomyopathy secondary to cardiac amyloidosis is an underdiagnosed, but treatable, cause of heart failure involving an extracellular deposition of misfolded protein. Hereby, we report a case of a female patient with history of nephrotic syndrome for 1 year who subsequently presented with symptoms of heart failure. The findings on cardiac imaging supported the suspicion of cardiac amyloidosis. Further laboratory workup for amyloidosis was pursued along with endomyocardial biopsy which confirmed amyloidosis-AL type. Patient was started on chemotherapy. The case underscores the importance of a timely diagnosis with the help of symptomatology and imaging along with a multidisciplinary approach for patient care.

A Massive Right Atrial Mass in Chronic Myelogenous Leukaemia: A Case Report and Literature Review.

Right atrial masses are rare and diagnosis can be difficult unless histopathological specimens are obtained. In addition, the clinical course is not well documented, thereby making diagnosis and management challenging. The mass can be associated with haemodynamic instability with the potential to cause obstructive shock and embolism. We present the case of a young woman with untreated chronic myelogenous leukaemia with a massive haemodynamically significant right atrial mass. The usefulness of multimodality imaging and a multidisciplinary approach for diagnosing and treating this condition is highlighted. LEARNING POINTS: Right atrial mass is rare and can lead to pulmonary embolism and haemodynamic instability.As chronic myelogenous leukaemia is associated with an increased risk of thromboembolism, thrombus should be considered in the differential diagnosis of intracardiac masses.Multimodality imaging is indicated to guide diagnosis and appropriate management; in case of diagnostic uncertainty, histopathology may be needed to obtain a definitive diagnosis.

Massive haemoptysis following recurrent ST-elevation myocardial infarction due to undiagnosed granulomatosis with polyangiitis.

Granulomatosis with polyangiitis (GPA) is a rare small-vessel vasculitis associated with high mortality without appropriate treatment. Acute ST-elevation myocardial infarction (STEMI) has been reported as an atypical presentation of GPA. We report a case of STEMI, shortly followed by subacute in-stent thrombosis with extensive thrombus burden in a 53-year-old male patient with undiagnosed GPA. After aggressive treatment with triple therapy consisting of aspirin, clopidogrel and rivaroxaban, He started to have haemoptysis. Despite the discontinuation of aspirin, he ended up with massive haemoptysis and acute respiratory failure necessitating endotracheal intubation. CT of the chest revealed bilateral ground-glass opacities consistent with diffuse alveolar haemorrhage. Extensive workup revealed positive antiproteinase 3 antibodies; hence, a diagnosis of GPA was made. He was treated with induction therapy consisting of methylprednisolone, mycophenolate mofetil, cyclophosphamide and rituximab, leading to a gradual improvement in his clinical conditions and subsequent extubation.

Refractory Shock Secondary to Denosumab-induced Severe Hypocalcaemia.

Denosumab is one of the most commonly used antiresorptive drugs for osteoporosis treatment and the prevention of skeletal-related events in cancer patients. The purpose of this case report is to highlight potentially life-threatening severe hypocalcaemia as a side effect of denosumab complicated by refractory shock that failed to respond to medical management including intravenous calcium, vasopressors and inotropes in an elderly man with a history of prostatic cancer. LEARNING POINTS: Denosumab is a commonly used antiresorptive drugs for the treatment of osteoporosis and to prevent skeletal-related events in patients with cancer.A common side effect of denosumab is hypocalcaemia; conditions associated with a higher risk of hypocalcaemia include chronic kidney disease, pre-existing hypocalcaemia, and metastatic cancer.Severe hypocalcaemia may induce cardiovascular manifestations such as hypotension, bradycardia, impaired cardiac contractility, impaired vascular tone, and arrhythmias.Shock results from diminished vascular smooth muscle tone and tends to occur with rapid severe hypocalcaemia; it is usually refractory to fluid and pressor therapy until hypocalcaemia is corrected.

Anomalous Aortic Origin of the Right Coronary Artery: A Case Report and Review of the Literature.

Patients with symptomatic or malignant anomalous aortic origin of the right coronary artery (AAORCA) warrant surgical treatment to decrease morbidity and mortality. Various surgical techniques have been implemented including unroofing, reimplantation and bypass grafting. A 43-year-old woman presented with intermittent chest pain due to malignant AAORCA and received saphenous bypass grafting, instead of reimplantation, due to intraoperative spasm. LEARNING POINTS: Various surgical methods are available for the management of anomalous aortic origin of the right coronary artery (AAORCA), preferably unroofing when the intramural segment can be identified.Hypoplasia of the proximal segment, an acute take-off angle, and close proximity to the intercoronary pillar or commissure are limitations to unroofing, and alternative approaches are more appropriate.Coronary artery bypass graft, with either arterial or venous graft, can be performed when unroofing and reimplantation are not feasible. Measuring the distal anastomosis flow may help with a decision regarding native coronary artery ligation. It remains undetermined whether arterial or venous grafts provide superior outcomes.

Therapeutic potential and molecular mechanisms of mycophenolic acid as an anticancer agent.

Mycophenolic acid (MPA) is the active metabolite of mycophenolate mofetil (MMF), an immunosuppressive drug approved for the prophylaxis of allograft rejection in transplant recipients. Recent advances in the role of the type II isoform of inosine-5'-monophosphate dehydrogenase (IMPDH2) in the tumorigenesis of various types of cancer have called for a second look of MPA, the first IMPDH2 inhibitor discovered a hundred years ago, to be repurposed as an anticancer agent. Over a half century, a number of in vitro and in vivo experiments have consistently shown anticancer activity of MPA against several cell lines obtained from different malignancies and murine models. However, a few clinical trials have been conducted to investigate its anticancer activity in humans, and most of which have shown unsatisfactory results. Understanding of available evidence and underlying mechanism of action is a key step to be done so as to facilitate further investigations of MPA to reach its full therapeutic potential as an anticancer agent. This article provides a comprehensive review of non-clinical and clinical evidence available to date, with the emphasis on the molecular mechanism of action in which MPA exerts its anticancer activities: induction of apoptosis, induction of cell cycle arrest, and alteration of tumor microenvironment. Future perspective for further development of MPA to be an anticancer agent is extensively discussed, with the aim of translating the anticancer property of MPA from bench to bedside.

Mycophenolic Acid and Its Pharmacokinetic Drug-Drug Interactions in Humans: Review of the Evidence and Clinical Implications.

Mycophenolic acid (MPA) is an immunosuppressive agent commonly prescribed during posttransplant periods for the prevention of acute and chronic rejection following organ transplantation. Compelling evidence has demonstrated a pivotal role of the exposure level of MPA in determining the rate of allograft rejection as well as the incidence of adverse outcomes, such as gastrointestinal complaints and myelosuppression. Because MPA has wide interindividual pharmacokinetic (PK) variability, the importance of maintaining the MPA concentration levels within its therapeutic range is clear. In addition, due to its complex PKs, MPA is prone to inadvertently develop PK drug-drug interactions (DDIs) with many agents, some of which are commonly used in organ transplant recipients. Failure to acknowledge such clinically significant PK DDIs between MPA and other coadministered drugs could potentially lead to devastating outcomes, ie, the occurrence of acute and chronic allograft rejection or the development of severe adverse events. The rationale to avoid concomitant use of certain drugs with MPA has been established; however, there is a lack of comprehensive literature to guide clinicians and medical professionals on the recognition and monitoring of potential PK DDIs when MPA is prescribed. In this article we comprehensively review, summarize, and discuss previous clinical studies that investigated the impact of coadministered drugs on the PK of MPA, with a major focus on the PK DDIs between MPA and commonly coadministered drugs.

Doxorubicin and its proarrhythmic effects: A comprehensive review of the evidence from experimental and clinical studies.

The cancer burden on health and socioeconomics remains exceedingly high, with more than ten million new cases reported worldwide in 2018. The financial cost of managing cancer patients has great economic impact on both an individual and societal levels. Currently, many chemotherapeutic agents are available to treat various malignancies. One of these agents is doxorubicin, which was isolated from Streptomyces peucetius in the 1960s. Doxorubicin is frequently administered in combination with other agents as a mainstay chemotherapeutic regimen in many settings, since there is well-documented evidence that it is effective in eliminating malignant cells. Doxorubicin exerts its anti-tumor properties through DNA intercalation and topoisomerase inhibition. It also contains a quinone moiety which is susceptible to redox reactions with certain intracellular molecules, thereby leading to the production of reactive oxygen species. The oxidative stress following doxorubicin exposure is responsible for its well-documented cardiotoxicity, impairing cardiac contractility, ultimately resulting in congestive heart failure. Despite the cumulative evidence noting its adverse effects on the heart, limited information is available regarding the mechanistic association between doxorubicin and cardiac arrhythmias. There is compelling evidence to suggest that doxorubicin also causes proarrhythmic effects. Several case reports and studies in cancer patients have attributed many arrhythmic events to doxorubicin, some of which are life-threatening such as complete heart block and ventricular fibrillation. In this review, reports regarding the potential arrhythmic complications associated with doxorubicin from previous studies investigating the effects of doxorubicin on cardiac electrophysiological properties are comprehensively summarized and discussed. Consistencies and controversial findings from in vitro, in vivo, ex vivo, and clinical studies are presented and mechanistic insights regarding the effects of doxorubicin are also discussed.